Pilocarpine and Artificial Saliva for the Treatment of Xerostomia and Xerophthalmia of Sjögren's Syndrome: A double blind control trial

Abstract

Background

Sjögren's Syndrome (SS) is associated with xerostomia and xerophthalmia. Pilocarpine stimulates the secretion of saliva.

Objectives

Investigate and compare the efficacy of pilocarpine and artificial saliva as symptomatic treatments for xerostomia and xerophthalmia in patients with SS.

Patients and Methods

A double-blind, randomized, controlled study was performed. 72 patients with SS were assigned randomly to receive ten drops of pilocarpine (5 mg) or 10 drops of artificial saliva, orally, t.i.d.for 12 weeks. Patients were evaluated at baseline and periodically throughout the study by whole saliva and tear flow for global assessment of their dryness as well as for any adverse effects.

Results

Patients receiving pilocarpine had a statistically significant improvement in their salivary flow (p< 0.0001), lachrymal flow (p< 0.0001), and their subjective global assessment (p< 0.0001), compared with patients on artificial saliva. The most common side effects were sialorrhea and nausea.

Limitations

As the pilocarpine was in solution (drops), it was possible for the dosage to become inaccurate.

Conclusions

Pilocarpine is more effective than artificial saliva for enhancing salivary and lachrymal secretion in patients with SS. This is the first study comparing the efficacy of pilocarpine and artificial saliva as treatments for xerostomia and xerophthalmia in SS.

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The synergistic activities of the combination of TNF-α, IL-17A, and IFN-γ in epidermal keratinocytes

Abstract

Psoriasis vulgaris is a common chronic inflammatory skin disease characterized by abnormal epidermal hyperplasia and the infiltration of cells including neutrophils and T cells.¹ Th1 and Th17 cells particularly infiltrate psoriatic lesions, and they are thought to play critical roles in the pathogenesis. Psoriatic keratinocytes are morphologically abnormal, and they are also involved in the cell infiltration.

Antibody agents that block key cytokines have been successfully used clinically for psoriasis.

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A Review of Clinical Trial Registry Use in Dermatology Systematic Reviews

Abstract

An inherent qualification of systematic reviews is that they attempt to collate all relevant empirical evidence. While properly conducted systematic reviews are considered the gold standard for determining health care policy and clinical decision making, they are vulnerable to publication bias¹. Publication bias occurs when statistically nonsignificant data from unpublished literature are omitted from systematic reviews and meta-analyses².

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Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue

Summary

Background

Eccrine sweat glands (ESGs) are critical for thermoregulation and involved in wound healing. ESGs have traditionally been considered as separate skin appendages without connection to the pilosebaceous unit (PSU). However, recent preliminary evidence has encouraged the hypothesis that PSU and ESG are more interconnected than previously thought.

Objective

To reevaluate the morphology of human skin adnexa with an integrated 3D perspective in order to explore the possible interconnections that the PSU and the ESG may form.

Methods

A systematic 3D reconstruction method of skin sections, direct visualization of human scalp follicular unit transplant grafts and a scalp strip ex vivo were used to validate and further explore the hypothesis.

Results

We demonstrate that the coiled portion of most ESGs is morphologically integrated into the PSU of human scalp skin and forms a structural unit that is embedded into a specific, HF-associated region of dermal white adipose tissue (dWAT). This newly recognized unit is easily accessible and experimentally tractable by organ culture of follicular units and can be intravitally visualized.

Conclusions

We propose a model of functional human skin anatomy in which ESGs are closely associated with the PSU and the dWAT to form a common homeostatic tissue environment, which may best be encapsulated in the term adnexal skin unit (aSU). The challenge now is to dissect how each component of this superstructure of human skin functionally cooperates with and influences the other under physiological conditions, during regeneration/repair and in selected skin diseases.

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Correction of T cell deficiency in ZAP-70 knockout mice by simple intraperitoneal adoptive transfer of thymocytes

Summary

The tyrosine kinase ZAP-70 (zeta-chain associated protein of 70 kDa) plays a key role in T cell development and signaling. In the absence of ZAP-70, T cell development is arrested in the CD4⁺CD8⁺ double positive stage, thus ZAP-70 homozygous knockout (ZAP-70^-/-) mice have no mature T cells in their peripheral lymphoid organs and blood, causing severe immunodeficiency.

We investigated the early kinetics and long-term effects of wild-type thymocyte transfer on T cell repopulation in ZAP-70^-/- mice. We used a single intraperitoneal (ip.) injection to deliver donor thymocytes to the recipients.

Here, we show that after ip. injection donor thymocytes leave the peritoneum through milky spots in the omentum and home to the thymus, where most probably donor-originated CD4^-CD8^- double negative thymocytes restore T cell development and the disrupted thymic architecture. Subsequently, newly developed, donor-originated, single-positive αβ T cells appear in peripheral lymphoid organs, where they form organized T cell zones. The established chimerism was found to be stable, as donor-originated cells were present in transferred ZAP-70^-/- mice as late as 8 months after ip. injection.

We demonstrate that a simple, ip. injection of ZAP-70^+/+ thymocytes is a feasible method for the long-term reconstitution of T cell development in ZAP-70 deficient mice. This article is protected by copyright. All rights reserved.

Immunoassay methods used in clinical studies for the detection of anti-drug antibodies to adalimumab and infliximab

Summary

Objective: To examine the assay formats used to detect anti-drug antibodies (ADA) in clinical studies of the anti-TNF monoclonal antibodies adalimumab and infliximab in chronic inflammatory disease and their potential impact on pharmacokinetic and clinical outcomes.

Methods: Using findings of a recent systematic literature review of the immunogenicity of 11 biologic/biosimilar agents, we conducted an ancillary qualitative review of a subset of randomized controlled trials and observational studies of the monoclonal antibodies against anti-tumor necrosis factor adalimumab and infliximab.

Results: Among studies of adalimumab and infliximab, the immunoassay method used to detect antibodies was reported in 91/111 (82%) and 154/206 (75%) adalimumab and infliximab studies, respectively. In most adalimumab and infliximab studies, an enzyme-linked immunosorbent assay or radioimmunoassay was used [85/91 (93%) and 134/154 (87%), respectively]. ADA incidence varied widely across assays and inflammatory diseases (adalimumab, 0–87%; infliximab, 0–79%). Pharmacokinetic and clinical outcomes were only reported for ADA-positive patients in 38/91 (42%) and 61/154 (40%) of adalimumab and infliximab studies, respectively. Regardless of assay format or biologic used, ADA formation was associated with lower serum concentrations, reduced efficacy, and elevated rates of infusion-related reactions.

Conclusion: Consistent with previous recommendations to improve interpretation of immunogenicity data for biologics, greater consistency in reporting of assay methods and clinical consequences of ADA formation may prove useful. Additional standardization in immunogenicity testing and reporting, application of modern, robust assays that satisfy current regulatory expectations, and implementation of international standards for marketed products may help improve our understanding of the impact of immunogenicity to biologics. This article is protected by copyright. All rights reserved.

A quarter of patients with type 1 diabetes have co-existing non-islet autoimmunity; the findings of a UK population-based family study

Summary

Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA), and gastric H⁺/K⁺-ATPase (ATPA) and their genetic associations in a well-characterised population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available. Autoantibodies in sera from 1072 patients (males/females 604/468; median age 11.8 years, median T1D duration 2.7 months) were measured by radioimmunoassays; HLA class II risk genotype was analysed in 973 (91%) using PCR-SSP. The prevalence of TGA (and/or history of CD), TPOA and ATPA in patients was 9.0%, 9.6%, and 8.2%, respectively; 3.2% had two or more autoantibodies. Females were at higher risk of multiple autoimmunity; TGA/CD were associated with younger age, and TPOA with older age. ATPA were uncommon in patients under 5 years, and more common in older patients. Anti-glutamate decarboxylase autoantibodies were highly predictive of co-existing TPOA/ATPA. TGA/CD were associated with HLA DR3-DQ2, with the DR3-DQ2/DR3-DQ2 genotype conferring the highest risk, followed by DR4-DQ8/DR4-DQ8. ATPA were associated with DR3-DQ2, DRB1*0404 (in males) and the DR3-DQ2/DR4-DQ8 genotype (in females). TPOA were associated with the DR3-DQ2/DR3-DQ2 genotype. Almost one quarter of patients diagnosed with T1D under 21 years have at least one other organ specific autoantibody. HLA class II genetic profiling may be useful in identifying those at risk of multiple autoimmunity. This article is protected by copyright. All rights reserved.

Separation of plasma-derived exosomes into CD3(+) and CD3(-) fractions allows for association of immune cell and tumor cell markers with disease activity in HNSCC patients

Summary

Head and neck squamous cell carcinoma (HNSCC) is a highly immunosuppressive malignancy. Exosomes in HNSCC patients' plasma are enriched in inhibitory cargo and mediate immunosuppression. As these exosomes are products of various cells, the cellular origin of immunoregulatory proteins they carry is unknown. To test whether tumor- or T cell-derived exosomes in patient's plasma are immunosuppressive and impact on disease activity, we separated CD3(-) from CD3(+) exosomes by immunocapture using anti-CD3 Abs. The exosome protein cargo was evaluated for immunoregulatory proteins using on-bead flow cytometry. Tumor protein-enriched CD3 (-) exosomes were CD44v3(+). Surprisingly, mean levels of PD-L1, CTLA-4 and COX-2 were similar in CD3(+) and CD3(-) exosomes, although the latter induced higher (p<0.0025) ex vivo apoptosis of CD8(+) T cells and greater (p<0.005) conversion of CD4+ T cells to CD4(+)CD39(+) Treg. CD3(+) and CD3(-) exosomes carrying high levels of immunosuppressive proteins were highly effective in mediating these functions. Exosomes of patients with UICC stage III/IV disease had higher levels of PD-L1 and COX-2 than stage I/II patients (p<0.005). Patients with nodal involvement had exosomes with the higher inhibitory protein content than N0 patients (p<0.03). CD3(+) and CD3(-) exosomes of HNSCC patients had higher PD-L1, COX-2 and CD15s levels than healthy donors' exosomes (p<0.009), although levels of immunostimulatory OX40 or OX40L were not different. By isolating CD3(-)/CD44v3-enriched and CD3(+) exosomes from plasma, the cellular origins of immunoregulatory proteins they carry were identified. Association of exosome molecular profiles with disease progression supports the exosome potential as future cancer biomarkers. This article is protected by copyright. All rights reserved.

Sunscreen use in schools: a content analysis of U.S. state laws

A technique for teaching and photo-documentation of direct endoscopic rigid oesophagoscopy

Abstract

Direct oesophagoscopy is largely a diagnostic procedure performed for a variety of symptoms (e.g. unilateral otalgia or odonophagia) or as part of a panendoscopy to exclude a synchronous primary; therefore good visualisation of abnormal mucosa is essential. The current standard oesophagoscopy technique involves direct visualisation from approximately 25cm down a narrow, illuminated oesophagoscope limiting visualisation of abnormal mucosa. Usually performed by a single operator, the technique is difficult to teach, as the trainee is unable to visualise what the trainer is seeing endoluminally and visa versa.

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Lipomatoses

Summary

Lipomatoses are benign proliferations of adipose tissue, often with typical distribution patterns, which usually occur without clear causes. In contrast to circumscribed lipomas, they develop diffusely and symmetrically and are not surrounded by a fibrous pseudocapsule.

The most common form is benign symmetric lipomatosis (BSL; Launois-Bensaude syndrome), of which four types are distinguished based on the distribution pattern of hyperplastic adipose tissue. The etiology and pathogenesis of the disease are still largely unknown, although some forms appear to have a hereditary basis or to be associated with increased alcohol consumption. In some cases, mitochondrial dysfunctions have been detected. Lipomatoses may be solitary, but may also be associated with other symptoms or illnesses (comorbidity). Effective drug therapies are not known, but surgical procedures can alleviate the symptoms.

Lipomatosis dolorosa, which can be distinguished from BSL, occurs predominantly in middle-aged women and is characterized by proliferation of adipose tissue and severe pain in the affected areas. Various differential diagnoses and concomitant illnesses need to be considered, in particular depression. There are no evidence-based recommendations for therapy. Repetitive lidocaine infusions can achieve temporary improvement. Recurrence after surgical intervention is not uncommon, but long-term success is also possible.

Dermatologic surgery in children: an update on indication, anesthesia, analgesia and potential perioperative complications

Summary

Background

Children undergoing dermatosurgical procedures require, unlike adults, particular attention; the administration of various analgesics, anesthetics or sedatives requires a thorough knowledge of drug pharmacokinetics and pharmacodynamics. Furthermore, there are concerns that drugs used for sedation/general anesthesia may result in anesthetic/analgesic complications in children undergoing surgery, with a risk of impaired mental development.

Objectives

Based on our clinical experience and a literature review, we illustrate the most commonly used analgesic, anesthetic and sedative drugs in pediatric dermatosurgery, and identify risk factors and complications following dermatosurgical procedures.

Results

Topical anesthetics can be used in children for superficial dermatologic procedures or prior to infiltration anesthesia. Maximum recommended doses based on body weight should be calculated in order to avoid overdosage of local anesthetics. General anesthesia in dermatosurgery is considered safe and has a low rate of side effects. However, caution is advised in children under the age of one due to potential long-term neurological side-effects. NSAIDs and opioids play a significant role in analgesia for children.

Conclusions

This article reviews currently available data on analgesia, anesthesia and complications that may arise in pediatric dermatosurgery. These data may be useful in optimizing the safety and quality of care and in improving parent counseling.

Long-distance alteration of lymphatic drainage in a melanoma patient after axillary lymph node dissection

Huge pedunculated tumor of the thigh

Is manual acne therapy medically necessary?

Asymptomatic yellowish papules on the upper arms

Issue Information

GATA-3 staining in primary cutaneous apocrine cribriform carcinoma: usefulness To differentiate it from breast cancer metastasis

ABSTRACT

BACKGROUND

Primary cutaneous apocrine cribriform carcinoma (PCACC) is a rare tumor, clinically appearing as a solitary nodule, mostly involving extremities of females and this lesion usually raise a differential diagnosis with metastatic cribriform carcinomas, especially breast cancer.

DESIGN

To study GATA3 expression in a series of 14 primary cutaneous cribriform carcinomas and to test this immunostaining usefulness to differentiate this tumor from metastatic breast cancer.

RESULTS

No primary cutaneous apocrine cribriform carcinoma express GATA3. Breast cancer metastasis express GATA3 in 100% of our studied cases.

CONCLUSION

Even when GATA3 expression has been reported in many benign and malignant adnexal tumors, mostly the sebaceous, follicular and apocrine ones, as well as in many other neoplasms, GATA3 staining to differentiate PCACC from skin breast cancer metastasis has a high negative predictive value. A positive GATA3 staining in this context should led to rule out PCACC with a high level of confidence.

Potential efficacy of a RNAi-based topical treatment for psoriasis

History of Morgellons disease: from delusion to definition

Influence of land use on the health of a detritivorous fish ( Ancistrus mullerae ) endemic to the Iguassu ecoregion: relationship between agricultural land use and severe histopathological alterations

Abstract

This study aimed to evaluate the histopathological biomarkers of the gills and liver of endemic catfish to test the hypothesis that, in environments under intense land use by agricultural activities, histopathological alterations occur more severely. Samples were collected by electrofishing in seven streams in the Lower Iguaçu basin quarterly from August 2015 to February 2016. The gills and livers were processed according to routine histological methods and examined by light microscopy. The histopathological alterations observed in fish from the streams with a higher percentage of natural vegetation cover were considered modest and indicated normal functioning of the organ (such as edema, hyperplasia, and leukocyte infiltration). As predicted, fish collected in streams with higher agricultural influence presented moderate to severe damage (aneurysm, vacuolization and cytoplasmic degeneration, and pyknotic nucleus). The abundance of chloride cells was significantly increased in the gills of Ancistrus mullerae collected in rural streams. In addition, in most streams, mucous cells were more abundant during the rainy period. Significant differences were observed in the histopathological index (HI) of the gills and livers, where severe histopathological alterations occurred in fish from streams with a higher agricultural influence. The observed alterations were more severe in the liver than in the gills, which are indeed related to the liver's key role in the detoxification of xenobiotics. We conclude that more severe histological alterations occurred in fish from streams with the highest land use by agricultural activities. Thus, our work provides important insight into the conservation and management of natural resources.

Exposure to hexavalent chromium in welders: Results of the WELDOX II field study

Abstract

Objectives

Exposure to hexavalent chromium (Cr(VI)) has been primarily studied in chromate production. Here, we measured personal exposure to respirable Cr(VI) together with airborne and urinary Cr and Ni in welders to explore levels and associations between various measures of exposure.

Methods:

Shift concentrations of Cr(VI), Cr, and Ni were measured in respirable welding fumes in 50 men who used either gas metal arc welding (GMAW) (n = 24) or tungsten inert gas welding (TIG) (n = 19) as their major technique. Cr and Ni were determined in pre- and post-shift urine samples. Concentrations below the limit of quantification (LOQ) were multiply imputed. Spearman correlation coefficients (r_s) were calculated with 95% confidence intervals (CIs) to explore associations between the exposure variables, and regression models were applied to estimate the effect of the parent metal on the urinary concentration.

Results:

Regarding the respirable Cr(VI), 62% of the measurements were below the LOQ, the 75^th percentile was 0.50 µg m⁻³_, and 8 out of 50 (16%) welders exceeded 1 µg m⁻³. The highest shift concentration that occurred as a result of shielded metal arc welding (SMAW) was 180 µg m⁻³. The Cr(VI) content in total Cr ranged from 4 to 82% (median 20%), although the concentration correlated with total Cr (r_s 0.55, 95% CI 0.46; 0.64). The correlation between Cr(VI) and Ni was weaker (r_s 0.42, 95% CI 0.34; 0.51) than that between total Cr and Ni in welding fumes (r_s 0.83, 95% CI 0.74; 0.92). Both Cr(VI) and total Cr influenced the urinary Cr concentrations in post-shift samples (P = 0.0008 and P ≤ 0.0001, respectively). The airborne shift exposure was a weaker determinant than the Cr content in pre-shift urine samples, which strongly correlated with post-shift urinary Cr (r_s 0.78, 95% CI 0.69; 0.87).

Conclusions:

The Cr(VI) content in total Cr varied considerably in welding fumes. The majority of welders using GMAW or TIG presented with shift concentrations of respirable Cr(VI) below 1 µg m⁻³. However, very high Cr(VI) concentrations may occur, for example in SMAW. The urinary concentration of total Cr, cannot be used to precisely determine the shift concentration of respirable Cr(VI) in welders.

Renal fungus ball in a patient with retroperitoneal fibrosis: Unique complication in a rare disease

Summary

Candida fungus ball is a rare presentation of urinary tract infections among adult patients and is associated with considerable morbidity. Because clinical signs are not specific, diagnosis is often delayed. Furthermore, treatment is occasionally difficult, and the approach to such cases varies widely among different centers. In this report, we describe a patient with retroperitoneal fibrosis who developed a renal fungus ball. Management of this challenging case is discussed, and review of the literature is presented.

Response of soil microbial communities to red mud-based stabilizer remediation of cadmium-contaminated farmland

Abstract

In this work, a field test was conducted to investigate the effects of heavy metal stabilizer addition on brown rice and microbial variables in a cadmium (Cd)-contaminated farmland from April to October in 2016. Compared with the control, red mud-based stabilizer (RMDL) effectively reduced the concentration of Cd in brown rice (with the removal rate of 48.14% in early rice, 20.24 and 47.62% in late rice). The results showed that adding 0.3 kg m⁻² RDML in early rice soil or soil for both early and late rice increased the microbial biomass carbon (MBC), the number of culturable heterotrophic bacteria and fungi, and the catalase activity in soil at different stages of paddy rice growth. Furthermore, there was no notable difference in the diversity of the bacterial species, community composition, and relative abundance at phylum (or class) or operational taxonomic unit (OTU) levels between the control and treatment (RMDL addition) groups. In a word, RMDL could be highly recommended as an effective remediation stabilizer for Cd-contaminated farmland, since its continuous application in paddy soil cultivating two seasons rice soil could effectively decrease the Cd content in brown rice and had no negative impact on soil microorganisms.

Efficacy of MAS063DP lotion vs 0.02% triamcinolone acetonide lotion in improving post-ablative fractional CO2 laser resurfacing wound healing: a split-face, triple-blinded, randomized, controlled trial

Abstract

Proven as effective acne scar treatment, ablative fractional carbon dioxide (AFCO₂) laser requires post-laser wound healing care. MAS063DP is a multicomponent nonsteroidal anti-inflammatory moisturizer for effective post-laser treatment. This study compares the efficacy of MAS063DP and 0.02% triamcinolone acetonide (TA) lotion for post-laser wound healing and complications. A split-face, triple-blinded, clinical study was performed in 16 patients, aged 20–50 years, receiving AFCO₂ on both sides of the face, with MAS063DP on one side and 0.02% TA on the other side for 7 days twice daily. Digital photography, hemoglobin, and melanin index at baseline were obtained immediately after laser treatment and then at days 3, 5, 7, and 30. Erythema, edema, crusting, adverse effects, and post-inflammatory hyperpigmentation (PIH) were followed every visit. Sixteen patients, mean age 38.6 (8.4) years, with moderate–severe atrophic scar and skin phototype III–IV completed the study. Clinical improvement of edema, erythema, crusting, and hyperpigmentation was observed from day 3 to day 30 (P < 0.001), with no statistically significant difference in both groups. There was also no statistical difference of hemoglobin, melanin index, and texture at days 3, 5, 7, and 30. Melanin index at day 30 was significantly less than baseline in both MAS063DP and 0.02% TA. With PIH in 50% of cases, both treatments demonstrated good safety profiles and no serious adverse reactions. MAS063DP could be an effective treatment for post-laser wound healing and complications, compatible to 0.02% TA.

The in-hospital burden of hidradenitis suppurativa in patients with inflammatory bowel disease: a decade nationwide analysis from 2004 to 2014

Abstract

Background

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that significantly affects the patient's quality of life. Multiple studies have shown a strong association between HS and inflammatory bowel disease (IBD). Our primary goal was to explore the in-hospital burden of HS on patients with IBD. Our secondary goal was to establish unique baseline characteristics and comorbidities of IBD patients with HS.

Methods

This was a retrospective cohort study using the National Inpatient Sample (NIS) database for the years 2004 through 2014. All patients with ICD-9 CM codes for any diagnosis of IBD and HS were included. The primary outcome was the medical and financial burden of HS on patients with IBD. Medical burden was measured by in-hospital morbidity and mortality, and financial burden was measured by resource utilization.

Results

A total of 3,079,332 admissions with IBD were recorded, of which 4369 had a concomitant diagnosis of HS. IBD-HS patients were significantly younger and mostly African-American females; they were more likely to be smokers, obese, and have diabetes mellitus, depression, and anemia. There was no mortality difference between the IBD-HS and IBD-only groups; nevertheless, there was a higher likelihood of developing sepsis in the IBD-HS cohort (4.9% vs. 2.6%; P < 0.001). Patients with IBD-HS had an increased hospital length of stay (5 vs. 4 days; P < 0.001) and higher total hospitalization costs ($13,272 vs. $12,237; P = 0.013).

Conclusions

This large-scale study strengthens the evidence that these two inflammatory conditions are truly associated and establishes their joint effect on overall morbidity, mortality, and resource utilization.

Recent advances and development in epidermal and dermal drug deposition enhancement technology

Abstract

Skin is the largest and easily accessible organ of the body. Increases in incidences of dermatological disorders, demand for drug targeting, and patient compliance have increased the popularity of topical drug delivery amongst the people. However, drug delivery across the skin is still a challenge for researchers because permeation of maximum drugs is hindered by the upper layer of the epidermis (stratum corneum). Several approaches like use of chemical permeation enhancers and physical methods such as sonophoresis, iontophoresis, electroporation, microneedles, etc., have been used to deliver the drugs topically. These methods of topical drug delivery have some limitations and drawbacks. Therefore new techniques based on nano drug delivery system such as ultradeformable liposomes, nanostructured lipid carriers, nanoemulsions, solid lipid nanoparticles, lipospheres, nanoparticles, and ethosomes have been exploited for enhancing epidermal and dermal drug deposition. Development of these nanosytems requires a good understanding of mechanism of drug permeation, physicochemical properties of drug and carriers, and technological advancements in methodology. Therefore, this article covers recent advances in epidermal and dermal drug deposition enhancement approaches, biopharmaceutical challenges with dermal drug delivery, issues in formulation development, and regulatory aspects of nanosystem. This review article also discusses the concern of topical drug delivery in immunization, gene delivery, and cosmeceuticals.

Cutaneous Refractile Foreign Body Microemboli with Intravascular Injection of Oral Medication

Abstract

Injection drug abuse (IDA) is known to cause a spectrum of systemic and cutaneous complications. Despite the increasing incidence of IDA around the world, there is a paucity of literature discussing cutaneous complications from a dermatopathologic perspective. We present a case of a 35-year-old male with a complex medical history of Von Willebrand disease, Behcet's disease and diverticular disease. Following a sigmoidectomy/colostomy for diverticular perforation, he presented with fever and an indurated right arm displaying livedoid purpura. The right distal fingertips showed purpura with focal ulceration. A punch biopsy of the right wrist did not show evidence of inflammatory vasculitis or pyogenic infection, but instead demonstrated a focus of polarizing, refractile material occluding a dilated arterial lumen within the mid-dermis. The patient admitted to injecting a suspension of crushed ondansetron (Zofran) tablets into the antecubital area to control post-operative nausea. It is known that direct intravascular injection of foreign material can cause distal ischemia and necrosis, either by local vasoconstriction, thrombosis, or formation of microemboli, as in this patient. Our objective is to bring awareness to this rarely reported phenomenon, and to raise clinical suspicion for IDA when confronted with such a unique vasculopathic pattern.

Phacomatosis pigmentokeratotica: a case of HRAS mosaicism causing rhabdomyosarcoma

Abstract

A 17-year-old male presented with a large sebaceous naevus (SN) comprising part of his left face and scalp and a speckled lentiginous naevus (SLN) on his right trunk, hip, neck and scalp with a checkerboard pattern. His right oral hemimucosa showed extensive papillomatous lesions which were contiguous to the upper lip SN lesions. As for extracutaneous manifestations he suffered from cardiac, musculoskeletal and ocular alterations. On the other hand, he developed two primary rhabdomyosarcomas. DNA samples of the SN, SLN, the oral papillomatous hyperplasia and both rhabdomyosarcomas were analyzed by Sanger sequencing. A HRAS c.37G>C mutation was detected in all of them. Skin and blood DNA resulted wild type. PPK is characterized by the association of a sebaceous naevus with a papular naevus spilus and extracutaneous manifestations. Until not long ago, the etiopathogenetical hypothesis of didymosis was accepted. However, in 2013 Groesser et al. proved the existence of an activating HRAS mutation as the cause of this syndrome. A higher incidence of cancer has been observed in germline RASophaties. Furthermore, up to 30% of human cancers show dysregulation of the Ras-Raf-MEK-ERK pathways. In our patient, a HRAS mosaic mutation explains not only the cutaneous but also the extracutaneous manifestations. To our knowledge this is the first described case of PPK in which the existence of a HRAS mosaic mutation is the confirmed cause of rhabdomyosarcoma. Besides the HRAS 37G>C mutation has never been related to any type of rhabdomyosarcoma. Mosaicisms could be underdiagnosed causes of childhood tumours. As dermatologists we stand on a privileged position for the detection of these alterations.

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Methotrexate does not impede the development of contact allergy

Possible role of regional variation in allergic contact dermatitis: case report

Photo-contact allergy to octocrylene: a decreasing trend?

Issue Information

Allergic contact dermatitis caused by topical ketoconazole: a relevant issue? Review of ketoconazole-positive patch tests

Allergic contact dermatitis resulting from cetyl PEG/PPG-10/1 dimethicone in a deodorant cream

Vulvar oedema

Lymphomatoid contact dermatitis caused by limonene hydroperoxides confirmed by an exposure provocation test with the involved personal hygiene products

Spiramycin-related cutaneous eruption confirmed by patch testing

Propositional anaphors

Abstract

Propositions are posited to perform a variety of explanatory roles. One important role is being what is designated by a dedicated linguistic expression like a that-clause. In this paper, the case that propositions are needed for such a role is bolstered by defending that there are other expressions dedicated to designating propositions. In particular, it is shown that natural language has anaphors for propositions. Complement so and the response markers yes and no are argued to be such expressions.

Does needle biopsy cause an increased risk of extracapsular extension in the diagnosis of metastatic lymph node in melanoma?

Abstract

Background

Needle biopsy is a rapid, reliable, and reproducible procedure for histological confirmation of metastatic melanoma localization. Nonetheless, this procedure presents a theoretical risk of a mechanical weakening of the lymph node capsule with perinodal tumor seeding. The objective of the study was to evaluate the incidence of extracapsular extension after needle biopsy in comparison with surgical adenectomy in patients suspected of metastatic lymph node of melanoma.

Methods

We conducted a retrospective study of 1056 patients who underwent lymphadenectomy for melanoma between 2000 and 2016 in our unit. Sixty-nine patients were clinically and/or radiologically suspected of metastatic lymph node of melanoma. Patients were divided according to external lymph node biopsy or surgical adenectomy before lymphadenectomy. The primary endpoint was the histopathological identification of extracapsular extension in analyzed lymph nodes.

Results

The two populations were comparable except for the mitotic index, which was more frequently > 1/mm² in the group with surgical adenectomy (P = 0.005). The proportion of extracapsular extension was significantly greater in the needle biopsy group (28/37) than in patients who underwent surgical adenectomy (14/32) (P = 0.0067; OR = 4 [95% CI: 1.4–11]).

Conclusion

Our results suggest an increased risk of extracapsular extension after external lymph node biopsy in cases of suspicion of metastatic lymph node of melanoma. Thus, this encourages us to prefer surgical adenectomy in patients with suspected adenopathy accessible surgically. In other cases, needle biopsy should be carried out under radiological guidance using devices limiting tumor seeding.

Issue Information - TOC

Erratum

Predictive biomarkers and EGFR inhibitors in squamous cell carcinoma of head and neck (SCCHN)

Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma

Abstract

Background

This two-stage, phase IIa study (ClinicalTrials.gov: NCT01685008) investigated the antitumor activity and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients with relapsed or refractory (R-R) B-cell non-Hodgkin's lymphoma (NHL). CD19 is broadly expressed across the B-lymphocyte lineage, including in B-cell malignancies, but not by hematological stem cells.

Patients and methods

Patients aged ≥18 years, with R-R NHL progressing after ≥1 prior rituximab containing regimen were enrolled into subtype-specific cohorts: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), other indolent (i)NHL and mantle cell lymphoma (MCL). Treatment was MOR208, 12 mg/kg intravenously, weekly, for 8 weeks. Patients with at least stable disease could continue treatment for an additional 4 weeks. Those with a partial or complete response after 12 weeks could receive extended MOR208 treatment (12 mg/kg, either monthly or every second week) until progression. The primary endpoint was overall response rate.

Results

Ninety-two patients were enrolled: DLBCL (n=35), FL (n=34), other iNHL (n=11) and MCL (n=12). Responses were observed in DLBCL, FL and other iNHL cohorts (26%, 29% and 27%, respectively). They lasted ≥12 months in 5/9 responding patients with DLBCL, 4/9 with FL and 2/3 with other iNHL. Responses in nine patients are ongoing (>26 months in five instances). Patients with rituximab refractory disease showed a similar response rate and progression-free survival time to patients with non-refractory disease. The most common adverse events (any grade) were infusion-related reactions (IRRs; 12%) and neutropenia (12%). One patient experienced a grade 4 IRR and eight patients (9%) grade 3/4 neutropenia. No treatment-related deaths were reported.

Conclusions

MOR208 monotherapy demonstrated promising clinical activity in patients with R-R DLBCL and R-R FL, including in patients with rituximab refractory tumors. These efficacy data and the favorable safety profile support further investigation of MOR208 in phase II/III combination therapy trials in R-R DLBCL.

ClinicalTrials.gov number

NCT01685008

Colchicine in dermatology: A review

Abstract

Colchicine is an anti-inflammatory agent that has been used for decades for the treatment of various diseases including gout, familial Mediterranean fever and pericarditis and in recent years for dermatological indications including chronic urticaria, cutaneous vasculitis and psoriasis. Despite its efficacy in various cutaneous diseases, the use of colchicine may be limited by concerns over its side-effects and the potential for toxicity. This article reviews the current literature on the pharmacology of colchicine and its clinical applications in dermatology.

Dystrophic calcinosis cutis within burns, successfully treated with excision and secondary intention wound healing

Placental implantation over prior cesarean scar causes activation of fetal regulatory T cells

Abstract

Introduction

Maternal-fetal chimerism is miniscule, a testament to the integrity of the uteroplacental interface. The soundness of this border region is potentially altered through cesarean delivery of prior babies with uncertain consequences for the following pregnancies.

Methods

Using multicolor flow cytometry and quantitative PCR of non-inherited maternal antigens we performed a retrospective case control pilot study and formulated the null hypothesis that placental implantation over a prior uterine scar does not result in the presence of memory Treg (CD45RO+) in the fetus. We then performed a power calculation and performed a blinded, appropriately powered prospective case control study to test the null hypothesis.

Results

Fetuses born to mothers with prior uterine scar have a roughly five times higher maternal to fetal microchimerism when the placenta directly interacts with the uterine scar. Unlike exposure to antigens in adult life, in utero antigenic exposure induces tolerogenic (Treg) responses in fetuses and we here report the presence of fetal Treg with a memory phenotype (CD45RO+). However, we only find such CD45RO+ fetal Tregs when the placenta abuts the uterine scar (Risk Ratio = 5 [p < 0.05 CI:(1.448 to 17.27)]). These memory fetal Tregs are functionally highly suppressive compared to CD45RA-expressing fetal Tregs, and have specificity for non-inherited maternal antigens.

Conclusions

We found that uterine scars, in the case of our study these scars are from prior c-sections, fundamentally impair uterine integrity allowing for increased antigen exposure of the fetus; with our appropriately powered study we rejected the null hypothesis and accepted the alternative hypothesis that placental implantation over a prior uterine scar results in the presence of memory Treg (CD45RO+) in the fetus. Thus, our study demonstrates a previously unappreciated role for uterine integrity in limiting fetal antigenic exposure, a key element to avoid the formation of inappropriate tolerances by the fundamentally tolerogenic fetal immune system.

Placental implantation over a prior cesarian scar has consequences in the subsequent pregnancy. The number of Treg does not change but their phenotype of fetal Treg is now activated. Thus, a scar, if the placenta is in contact with it, is a breach of the uterine barrier with consequences in the fetal immune system.

Ethosuximide-induced Stevens–Johnson syndrome: Beneficial effect of early intervention with high-dose corticosteroid therapy

Abstract

We report two rare cases of childhood epilepsy patients who developed ethosuximide-induced Stevens–Johnson syndrome (SJS). Unlike typical SJS, the initial eruption of both patients presented well-demarcated, infiltrating firm papules mainly on the cheeks and the extensor aspects of the arms (case 1), and multiple vesicles on the soles and oral aphthosis (case 2), which closely mimicked viral exanthema. We diagnosed both patients with ethosuximide-induced SJS, based on the dosing period and the positive results of drug-induced lymphocyte stimulation test. Systemic corticosteroids are usually selected as a standard therapy for SJS, despite controversial results regarding their effectiveness. In case 1, an i.v. pulse therapy of methylprednisolone (30 mg/kg, 3 days consecutively) was initiated on day 7 from the onset of illness, and an i.v. immunoglobulin (400 mg/kg, 5 days consecutively) was added the following day. In case 2, an i.v. prednisone treatment (1 mg/kg, for 1 week) was initiated on day 4 from the onset. Eventually, the early therapeutic interventions resulted in good outcomes in both patients.

Case of deep vein thrombosis in a patient with advanced malignant melanoma treated with dabrafenib and trametinib

Immunocryosurgery as monotherapy for lentigo maligna or combined with surgical excision for lentigo maligna melanoma

Abstract

The incidence of lentigo maligna (LM), in situ (LM) or invasive (lentigo maligna melanoma, LMM), has increased during the last decades. Due to functional or cosmetic outcomes, optimal treatment with surgical excision may not be appropriate in some cases. We tried less invasive therapy, immunocryosurgery, as a single treatment for LM or combined with surgery for LMM, with better aesthetic results. Three patients with LM or LMM not amenable to complete surgical excision were selected. LMM patients underwent limited surgical resection of the invasive area. Subsequently, a combined treatment with topical imiquimod and cryosurgery was performed. The LM patient received immunocryosurgery directly. All of them were free of local and systemic disease at 48, 42 and 41 months after discontinuation of therapy. We consider that immunocryosurgery is an alternative option for LM or even for LMM (after removal of the invasive tissue with narrow margins) in poor surgical candidates, with good therapeutic, functional and cosmetic results.

Benign cephalic histiocytosis: A case with infiltration of CD1a-positive langerin-negative cells

Cutaneous infiltration of plasmacytoid dendritic cells and t regulatory cells in skin lesions of polymorphic light eruption

Abstract

Background

Polymorphic light eruption (PLE) is the most common autoimmune photodermatosis. Plasmacytoid dendritic cells (PDCs) are important mediators of innate anti-microbial immunity involved in the pathogenesis of many inflammatory skin diseases. In addition to PDCs, regulatory T cells (Tregs) are involved in controlling inflammation and adaptative immunity in skin by their immunosoppressive capacity.

Objective

The aim of the present study was to investigate the presence of PDCs and Tregs in photoexposed skin from PLE compared to healthy skin.

Methods

Patients with PLE diagnosis and healthy controls were recruited and underwent a photoprovocative test. A 4- mm punch biopsy was taken from the site of positive photoprovocation test reaction and immunohistochemistry for BDCA2 as marker for PDCs, CD4 and FOXP3 as markers for Tregs was performed. Double immunostain for FOXP3 and CD4 was performed as well.

Absolute counts for CD4, BDCA2 and FOXP3 were performed in at least 5 High Power Fields (HPF). Percentage of CD4, BDCA2 and CD4FOXP3 positive cells over the total inflammatory infiltrate was assessed for each case.

Results

We enrolled 23 patients and controls. BDCA2+ cells were present in 91.3% of PLE skin samples, and 100% of healthy volunteer. Both in PLE patients and healthy controls, PDCs distribution was mainly dermic (p<0.05).

Compared to healthy controls, both epidermic and dermic BDCA2+ cells count was significantly higher in PLE patients (p<0.05).

Both in PLE patients and healthy controls, Tregs distribution was mainly dermic (p<0.05).

The presence of both CD4+ cells and FOXP3+ cells was significantly higher in the dermis of PLE patients compared to controls (p<0.05). Relative percentages of cellular infiltrations confirmed these results.

Conclusions

D-PDCS and Tregs may play a significant role in the development of PLE and dermal distribution of PDCs in PLE skin biopsies seems to confirm a possible overlap with Cutaneous Lupus Erythematosus (CLE).

This article is protected by copyright. All rights reserved.

Focal facial hyperhidrosis associated with internal carotid artery dissection successfully treated with botulinum toxin A

Abstract

Hyperhidrosis affects up to 3% of the population⁽¹⁾. Secondary hyperhidrosis may be associated with infections, malignancies, endocrine or neurological diseases⁽²⁾. We report the first case of localized hyperhidrosis associated to Pourfour du Petit syndrome secondary to internal carotid artery dissection successfully and safely treated with botulinum toxin.

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The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: Analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study)

Abstract

Background

Psychological aspect and quality of life should be considered in treating patients with psoriasis.

Objective

We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis.

Methods

The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1,260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the psoriatic arthritis (PsA) screening and evaluation (PASE), dermatology life quality index (DLQI), MOS 36-item short-form health survey (SF-36), work productivity and activity impairment questionnaire psoriasis (WPAI: PSO), and medication satisfaction questionnaire (MSQ).

Results

Patients with a DLQI score>5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA), and had higher PASE scores than patients with DLQI≤5 (n = 266). The group of patients with exposed lesions (n=871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n=389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment, and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental).

Conclusion

The presence of exposed lesions has a negative impact on quality of life, mental health, and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

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Dermoscopic Features of Tungiasis

Abstract

Tungiasis is a parasitic infection caused by the sand flea Tunga penetrans. Tungiasis is prevalent in rural Central and South America, the Caribbean and sub-Saharan Africa.¹ In some endemic areas, the overall infestation prevalence exceeds 50 percent, and it remains an important public health problem for poor communities.^1,2 In some cases, the eruptions can mimic viral warts, furuncles, abscesses and paronychia.¹ Dermoscopy is reported to be a useful tool for differentiating between these and tungiasis lesions.^3,4 Moreover, the majority of cases have multiple lesions, with the ectoparasites causing more than 50 lesions in a single individual in some cases,⁵ and dermoscopy can help find the lesions. Despite the clinical utility of dermoscopy, no reports have assessed the significance of each dermoscopic finding in tungiasis. Here we report a case of tungiasis and we review the dermoscopic findings of 11 lesions of the patient to reveal the characteristic findings.

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Psoriatic arthritis screening by the dermatologist: development and first validation of the “PURE-4 scale”

Abstract

Background

Dermatologists are recommended to ask psoriasis patients about musculoskeletal complaints to allow early detection and treatment of psoriatic arthritis (PsA). Screening tools have been developed to help identifying patients warranting further rheumatologic assessment, but evidence suggests room for improvement in their diagnostic value and ease of use for outpatient practice.

Objective

To develop and internally validate a brief tool for dermatologists to screen patients to refer to a rheumatologist for PsA diagnosis.

Methods

After literature review, 23 items were selected, covering pain at various locations and inflammatory signs of PsA. The validation study was conducted in medically diagnosed psoriasis patients consecutively recruited between 2012-2014 (Saint Joseph Hospital, Paris, France). Patients were enrolled by a dermatologist who helped to complete the questionnaire. Diagnosis of PsA was established by a rheumatologist based on CASPAR criteria. Multivariate logistic regression models were performed to build the scale, assessing discrimination through sensitivity, specificity and area under the ROC curve (AUC). Final model was internally validated using bootstrapping techniques.

Results

168 patients were recruited, of whom 9 were excluded for known PsA and 21 did not attend the rheumatologist consultation. Out of 137 included patients (median age 43 years, 59.6% men), 21 (15.3%) had a PsA diagnosis. Final regression model retained 4 independent items, including evocative signs of dactylitis, inflammatory heel pain, bilateral buttock pain and peripheral joint pain with swelling in patients aged<50. A total score (the PURE-4) was computed (0-4 points) that demonstrated excellent discriminative power (AUC=87.6%; Sensitivity=85.7% and Specificity=83.6% at the threshold of ≥1/4 points), with no evidence for over-optimism in bootstrapped internal validation.

Conclusion

These findings demonstrate the good diagnostic properties of a new screening scale using only 4 easy-to-collect items. If confirmed in other populations, it may prove useful in outpatient dermatology clinics for triage of psoriasis patients requiring further assessment by the rheumatologist.

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Patients affected by Dent disease 2 could be predisposed to hidradenitis suppurativa

Abstract

Dent disease 2 (DD2) is a rare X-Linked disorder characterized by proximal tubule dysfunction. It is considered as mild variant of Lowe Syndrome (LS) and both conditions are secondary to OCRL1 gene mutations.¹ Mutations in this gene drastically reduce (<10%) inositol polyphosphate 5-phosphatase (OCRL1) activity.¹

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Rapid Improvement of Psoriasis in a Patient with Lung Cancer after Treatment with Erlotinib

Abstract

We report the case of a 48-year-old woman with a rapid improvement of her psoriasis after treatment with erlotinib.A metastasised non-small cell lung cancer (NSCLC) was diagnosed and the psoriasis treatment with ustekinumab was stopped which caused a flare up of her psoriasis.

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Enolase-1 expression in the stratum corneum is elevated with parakeratosis of atopic dermatitis and disrupts the cellular tight junction barrier in keratinocytes

Abstract

Objective

Previous studies have shown that enolase-1 (ENO1) in the stratum corneum (SC) is more highly expressed in patients with atopic dermatitis (AD) than in healthy individuals, suggesting that it is a novel biomarker for evaluating skin condition in patients with AD. However, the mechanism underlying high ENO1 expression in the SC and its pathological relevance in AD are unclear. In this study, the relationship between ENO1 expression and keratinization of epidermis was investigated and the role of high ENO1 expression in keratinocytes was characterized.

Methods

ENO1 expression and morphological characteristics were examined in SC from the cheeks of 24 patients with AD. Additionally, the localization of ENO1 in the excised human epidermis was observed. Moreover, to analyze the role of ENO1 in cellular barrier function, tight junction proteins (TJs) and trans-epithelial electrical resistance (TEER) in keratinocytes with ENO1 overexpression were evaluated. Furthermore, the localization of ENO1 and plasminogen in keratinocytes was evaluated by immunostaining, and the cellular barrier function in keratinocytes was examined after treatment with tranexamic acid (TXA).

Results

ENO1 expression was substantially correlated with the rate of nucleated corneocytes in AD. In addition, ENO1 localized in the basal to spinous layers, but was its expression dramatically decreased in healthy human SC. ENO1 overexpression in human epidermal keratinocytes reduced the expression of TJs (claudin-4, E-cadherin, tricellulin, and occludin) and TEER, and treatment with anti-ENO1 IgG reversed these effects. ENO1 co-localized with plasminogen in keratinocytes. Treatment with TXA rescued the ENO1-induced reductions in TJ and TEER expression.

Conclusion

We found a substantial correlation between ENO1 expression and the rate of nucleated corneocytes in AD and decreased ENO1 expression with nuclear disappearance. These results suggest that high ENO1 expression in the SC of AD is caused by deficient keratinization, which is an AD characteristic. Moreover, ENO1 overexpression in keratinocytes promoted dysfunction of TJ dynamics, leading to reduced integrity of the cellular barrier, and these effects might be mediated by plasmin activity. We propose that ENO1 is a useful indicator of parakeratosis and might have a potential role in cellular TJ barrier function in the epidermis.

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The desert wormwood (Artemisia herba-alba) – From Arabian folk medicine to a source of green and effective nanoinsecticides against mosquito vectors

Publication date: Available online 11 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Al Thbiani Aziz, Mohammed Ali Alshehri, Chellasamy Panneerselvam, Kadarkarai Murugan, Subrata Trivedi, Jazem A. Mahyoub, Mo'awia Mukhtar Hassan, Filippo Maggi, Stefania Sut, Stefano Dall'Acqua, Angelo Canale, Giovanni Benelli
The development of eco-friendly and effective insecticides is crucial for public health worldwide. Herein, we focused on the desert wormwood (Artemisia herba-alba), a plant widely used in Arabian traditional medicine, as a source of green nanoinsecticides against mosquito vectors, as well as growth inhibitors to be employed against microbial pathogens. Ag nanoparticles (AgNPs) fabricated with the A. herba-alba extract were tested against Indian and Saudi Arabian strains of Anopheles, Aedes and Culex mosquitoes. The chemical profile of the A. herba-alba extract was determined by LC-DAD-MS and ¹H NMR studies. Then, AgNPs were studied using UV–vis spectroscopy, XRD, FTIR spectroscopy, TEM, and EDX analyses. Artemisia herba-alba-synthesized AgNPs showed high larvicidal toxicity against mosquitoes from both Indian and Saudi Arabian strains. LC50 of AgNPs against Indian strains was 9.76 μg/ml for An. stephensi, 10.70 μg/ml for Ae. aegypti and 11.43 for Cx. quinquefasciatus whereas against Saudi Arabian strains it was 33.58 μg/ml for Ae. aegypti and 38.06 μg/ml for Cx. pipiens. In adulticidal experiments, A. herba-alba extract showed LC50 ranging from 293.02 to 450 μg/ml, while AgNP LC50 ranged from 8.22 to 27.39 μg/ml. Further, low doses of the AgNPs inhibited the growth of selected microbial pathogens. Overall, A. herba-alba can be further considered as a source of phytochemicals, with special reference to saponins, for effective and prompt fabrication of AgNPs with relevant insecticidal and bactericidal activity against species of high public health importance.

Graphical abstract

Hard onset therapy for functional hypoadduction and presbylaryngis: our experience in 22 patients

Abstract

Objectives

The hard onset, also known as a hard attack, or glottal onset, is a technique of vocal production in which the vocal folds are adducted prior to exhalation and forced open to begin phonation. In this study, we assessed the short-term efficacy of voice therapy incorporating hard onset techniques for patients with functional hypoadduction and presbyphonia. Design: Prospective cohort study. Setting: Tertiary academic medical center. Participants: Twenty-two patients with functional hypoadduction who underwent voice therapy, including hard-onset therapy, for 3 months. Main outcome measures: Vocal function pre-therapy and 3 months post-therapy assessed objectively by quantitative aerodynamic and acoustic analysis and subjectively by vocal handicap index (VHI) and grade, roughness, breathiness, asthenia, strain (GRBAS) scale. Results: Voice quality as graded by the VHI and GRBAS were statistically significantly improved following voice therapy. Objective comparisons reflected improvement in fundamental frequency, jitter, shimmer, normalized noise energy, and maximal phonation time. Conclusions: Voice therapy, including hard onset therapy, improved vocal quality and performance by both subjective and objective measures in patients with functional hypoadduction/presbyphonia.

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Successful subcutaneous desensitization in a patient with allergy to ixekizumab

Publication date: Available online 10 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Ruth Barranco Jimenez, Daiana Guillen Vera, Raquel Rivera-Díaz, Susana Cortijo-Cascajares, Ruth Mielgo Ballesteros, María del Carmen Diéguez Pastor

Use of pdC1-INH concentrate for long-term prophylaxis during pregnancy in hereditary angioedema with normal C1-INH

Publication date: Available online 10 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Juliana F.B. Garcia, Priscila Takejima, Camila Lopes Veronez, Marcelo V. Aun, Antonio A. Motta, Jorge Kalil, João Bosco Pesquero, Pedro Giavina-Bianchi

Simultaneous quantification of caffeine and chlorogenic acid in coffee green beans and varietal classification of the samples by HPLC-DAD coupled with chemometrics

Abstract

A chromatographic procedure (HPLC-DAD) using a relatively rapid gradient has been combined with a chemometric curve deconvolution method, multivariate curve resolution-alternating least squares (MCR-ALS), in order to quantify caffeine and chlorogenic acid in green coffee beans. Despite that the HPLC analysis (at these specific operating conditions) presents some coeluting peaks, MCR-ALS allowed their resolution and, consequently, the creation of a calibration curve to be used for the quantification of the analytes of interest; this procedure led to a high accuracy in the quantification of caffeine and chlorogenic acid present in the samples. In a second part of this study, the possibility of classifying the green coffee beans on the basis of their cultivar (Arabica or Robusta), by partial least squares discriminant analysis (PLS-DA) and soft independent modeling of class analogies (SIMCA), has been explored. SIMCA resulted in 100% of sensitivity and specificity for the Arabica class, while for the Robusta, it reached 66.7% of sensitivity and 100% of specificity, or 100% of sensitivity and 100% of specificity, depending on the extraction procedure followed prior to the chromatographic analysis; PLS-DA achieved 100% of correct classification independently of the procedure used for the extraction.

Wet deposition of atmospheric nitrogen contributes to nitrogen loading in the surface waters of Lake Tanganyika, East Africa: a case study of the Kigoma region

Abstract

Lake Tanganyika, an African Great Lake, is a complex tropical ecosystem that has been subjected to extreme climate-related changes in the last century, including seasonal changes in temperature and rainfall, decreased overall annual rainfall, and greater frequency of rainstorms. Atmospheric nitrogen (N) is an important component of the lake's N loading, but how long-term and seasonal changes in precipitation affect this loading still needs clarification. This study aimed to improve our understanding of the seasonal features of N deposition in the lake, by monitoring atmospheric N deposition concentrations and fluxes from March 2013 to February 2014. There was a significant temporal variation in wet N depositions in the study area. The distribution of the annual rainfall into major (March–May 299.8 mm) and minor (October–December 343.2 mm) rainy seasons translated into 20 and 30% of N deposition. In September and January–February, there was 10 and 12% precipitation, representing 43 and 7% of N deposition in the lake. Nitrogen deposition was highest in September due to farmlands' burning during the dry season (June–August), leading to N accumulation in the atmosphere. In conclusion, the pattern of N deposition appears to be driven by the unique climatic characteristics of the lake basin and to be closely associated with local anthropogenic activities.

Effects of sewage sludge modified by coal gasification slag and electron beam irradiation on the growth of Alhagi sparsifolia Shap. and transfer of heavy metals

Abstract

A greenhouse experiment was performed to investigate the feasibility of sewage sludge modified by coal gasification slag pretreatment and electron beam irradiation in soil application for cultivation of Alhagi sparsifolia Shap. The results showed that modified sewage sludge had an active effect on the growth of Alhagi sparsifolia Shap. The sandy soil and modified sludge at the volume ratio of 2:1 were optimal, and the growth potential of Alhagi sparsifolia Shap. was highest. In the sandy soil, the values of bioconcentration factor of most heavy metals were below 1.0 except for Zn and Cu. The average bioconcentration factor values of heavy metals in Alhagi sparsifolia Shap. decreased in a sequence of Zn>Cu>Ni> Mn>Co>Pb>Cr>Fe>V>Cd>Mo for all treatments. Alhagi sparsifolia Shap. could decrease the eco-toxicity and bioavailability of Ni, Fe, and Mo in all mixed soil, and Alhagi sparsifolia Shap. could reduce the eco-toxicity and bioavailability of all heavy metals discussed in this study (except for Mn) in the mixed soil of SS:MSS = 2:1.

Diagnosis and Management of Pemphigus: recommendations by an International Panel of Experts

Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management,

Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib: a 32-week open label extension study with optional narrow-band ultraviolet B

Global Burden of Urticaria: Insights from the 2016 Global Burden of Disease Study

Whole-exome sequencing reveals differences between nail apparatus melanoma and acral melanoma

Impact of a Smartphone Application on Skin Self-Examination Rates in Patients that are New to Total Body Photography: A Randomized Controlled Trial

The staining of clothing by sunscreens: a pilot study

Rapid improvement of prurigo nodularis with cyclosporine treatment

Patient satisfaction and preference of absorbable versus non-absorbable sutures for linear repairs

Rethinking Biotin Therapy for Hair, Nail, and Skin Disorders

Commentary: Skin cancer in the military

A technique for more precise distinction between catagen and telogen human hair follicles ex-vivo

In-office compounding of lidocaine-epinephrine: an option for anesthesia preparation prior to skin biopsy

The impact of underlying disease state on outcomes in patients with pyoderma gangrenosum: A national survey

It is unclear if the underlying disease affects the outcomes in pyoderma gangrenosum.

Comparative Effectiveness of Targeted Immunomodulators for the Treatment of Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis

The comparative effectiveness of available targeted immunomodulators for moderate-to-severe psoriasis has not been evaluated.

Suspended particulate matter determines physical speciation of Fe, Mn , and trace metals in surface waters of Loire watershed

Abstract

This study investigates the spatiotemporal variability of major and trace elements, dissolved organic carbon (DOC), total dissolved solids (TDS), and suspended particulate matter (SPM) in surface waters of several hydrosystems of the Loire River watershed in France. In particular, this study aims to delineate the impact of the abovementioned water physicochemical parameters on natural iron and manganese physical speciation (homoaggregation/heteroaggregation) among fine colloidal and dissolved (< 10 nm), colloidal (10–450 nm) and particulate (> 450 nm) phases in Loire River watershed. Results show that the chemistry of the Loire River watershed is controlled by two end members: magmatic and metamorphic petrographic context on the upper part of the watershed; and sedimentary rocks for the middle and low part of the Loire. The percentage of particulate Fe and Mn increased downstream concurrent with the increase in SPM and major cations concentration, whereas the percentage of colloidal Fe and Mn decreased downstream. Transmission electron microscopy analyses of the colloidal and particulate fractions (from the non-filtered water sample) revealed that heteroaggregation of Fe and Mn rich natural nanoparticles and natural organic matter to the particulate phase is the dominant mechanism. The heteroaggregation controls the partitioning of Fe and Mn in the different fractions, potentially due to the increase in the ionic strength, and divalent cations concentration downstream, and SPM concentration. These findings imply that SPM concentration plays an important role in controlling the fate and behavior of Fe and Mn in various sized fractions.

Graphical abstract

Physical speciation by heteroaggregation of (Fe-Mn) compounds: high [SPM] → [Fe-Mn] particulate faction; low {SPM] → [Fe-Mn] colloid-dissolved fraction.

Post-contrast acute kidney injury – Part 1: Definition, clinical features, incidence, role of contrast medium and risk factors

Abstract

Purpose

The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 2011 guidelines on the prevention of post-contrast acute kidney injury (PC-AKI). The results of the literature review and the recommendations based on it, which were used to prepare the new guidelines, are presented in two papers.

Areas covered in part 1

Topics reviewed include the terminology used, the best way to measure eGFR, the definition of PC-AKI, and the risk factors for PC-AKI, including whether the risk with intravenous and intra-arterial contrast medium differs.

Key Points

• PC-AKI is the preferred term for renal function deterioration after contrast medium.

• PC-AKI has many possible causes.

• The risk of AKI caused by intravascular contrast medium has been overstated.

• Important patient risk factors for PC-AKI are CKD and dehydration.

Determination of glomerular filtration rate (GFR) from fractional renal accumulation of iodinated contrast material: a convenient and rapid single-kidney CT-GFR technique

Abstract

Objectives

To develop a convenient and rapid single-kidney CT-GFR technique.

Methods

One hundred and twelve patients referred for multiphasic renal CT and 99mTc-DTPA renal dynamic imaging Gates-GFR measurement were prospectively included and randomly divided into two groups of 56 patients each: the training group and the validation group. On the basis of the nephrographic phase images, the fractional renal accumulation (FRA) was calculated and correlated with the Gates-GFR in the training group. From this correlation a formula was derived for single-kidney CT-GFR calculation, which was validated by a paired t test and linear regression analysis with the single-kidney Gates-GFR in the validation group.

Results

In the training group, the FRA (x-axis) correlated well (r = 0.95, p < 0.001) with single-kidney Gates-GFR (y-axis), producing a regression equation of y = 1665x + 1.5 for single-kidney CT-GFR calculation. In the validation group, the difference between the methods of single-kidney GFR measurements was 0.38 ± 5.57 mL/min (p = 0.471); the regression line is identical to the diagonal (intercept = 0 and slope = 1) (p = 0.727 and p = 0.473, respectively), with a standard deviation of residuals of 5.56 mL/min.

Conclusion

A convenient and rapid single-kidney CT-GFR technique was presented and validated in this investigation.

Key Points

• The new CT-GFR method takes about 2.5 min of patient time.

• The CT-GFR method demonstrated identical results to the Gates-GFR method.

• The CT-GFR method is based on the fractional renal accumulation of iodinated CM.

• The CT-GFR method is achieved without additional radiation dose to the patient.

Health risk assessment of drinking arsenic-containing groundwater in Hasilpur, Pakistan: effect of sampling area, depth, and source

Abstract

Currently, several news channels and research publications have highlighted the dilemma of arsenic (As)-contaminated groundwater in Pakistan. However, there is lack of data regarding groundwater As content of various areas in Pakistan. The present study evaluated As contamination and associated health risks in previously unexplored groundwater of Hasilpur-Pakistan. Total of 61 groundwater samples were collected from different areas (rural and urban), sources (electric pump, hand pump, and tubewell) and depths (35–430 ft or 11–131 m). The water samples were analyzed for As level and other parameters such as pH, electrical conductivity, total dissolved solids, cations, and anions. It was found that 41% (25 out of 61) water samples contained As (≥ 5 μg/L). Out of 25 As-contaminated water samples, 13 water samples exceeded the permissible level of WHO (10 μg/L). High As contents have been found in tubewell samples and at high sampling depths (> 300 ft). The major As-contaminated groundwater in Hasilpur is found in urban areas. Furthermore, health risk and cancer risk due to As contamination were also assessed with respect to average daily dose (ADD), hazard quotient (HQ), and carcinogenic risk (CR). The values of HQ and CR of As in Hasilpur were up to 58 and 0.00231, respectively. Multivariate analysis revealed a positive correlation between groundwater As contents, pH, and depth in Hasilpur. The current study proposed the proper monitoring and management of well water in Hasilpur to minimize the As-associated health hazards.

On Rationales for Cognitive Values in the Assessment of Scientific Representations

Abstract

Cognitive values like simplicity, broad scope, and easy handling are properties of a scientific representation that result from the idealization which is involved in the construction of a representation. These properties may facilitate the application of epistemic values to credibility assessments, which provides a rationale for assigning an auxiliary function to cognitive values. In this paper, I defend a further rationale for cognitive values which consists in the assessment of the usefulness of a representation. Usefulness includes the relevance of a representation regarding the investigation of a given problem and its practicability for the users. This rationale builds on the claim that any evaluation of scientific representations should pursue two aims: providing information about their credibility and providing information about their usefulness. Cognitive values relating to the usefulness of a representation and epistemic values relating to its credibility both perform a first-order function. Cognitive values are abstract, and several values with first-order functions may conflict in their application. Thus, in order for cognitive values to account for the sort of problem that is to be investigated by means of a representation, they need to be appropriately specified and weighed. Comprehensiveness, complexity, high resolution, and easy handling, for instance, may be required in a first-order function for model-based prediction of regional climate impacts but not for explaining how the global climate system works. Specifying and weighing cognitive and epistemic values relative to a given problem is a legitimate second-order function of social values.

Low power lasers on genomic stability

Publication date: Available online 10 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Larissa Alexsandra da Silva Neto Trajano, Luiz Philippe da Silva Sergio, Ana Carolina Stumbo, Andre Luiz Mencalha, Adenilson de Souza da Fonseca
Exposure of cells to genotoxic agents causes modifications in DNA, resulting to alterations in the genome. To reduce genomic instability, cells have DNA damage responses in which DNA repair proteins remove these lesions. Excessive free radicals cause DNA damages, repaired by base excision repair and nucleotide excision repair pathways. When non-oxidative lesions occur, genomic stability is maintained through checkpoints in which the cell cycle stops and DNA repair occurs. Telomere shortening is related to the development of various diseases, such as cancer. Low power lasers are used for treatment of a number of diseases, but they are also suggested to cause DNA damages at sub-lethal levels and alter transcript levels from DNA repair genes. This review focuses on genomic and telomere stabilization modulation as possible targets to improve therapeutic protocols based on low power lasers. Several studies have been carried out to evaluate the laser-induced effects on genome and telomere stabilization suggesting that exposure to these lasers modulates DNA repair mechanisms, telomere maintenance and genomic stabilization. Although the mechanisms are not well understood yet, low power lasers could be effective against DNA harmful agents by induction of DNA repair mechanisms and modulation of telomere maintenance and genomic stability.

Laser Assisted Anticancer Activity of Benzimidazole Based Metal Organic Nanoparticles

Publication date: Available online 9 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): P.A. Praveen, R. Ramesh Babu, P. Balaji, A. Murugadas, M.A. Akbarsha
Recent studies showed that the photothermal therapy can be effectively used for the targeted cancerous cells destruction. Hence, in the present study, two benzimidazole based metal organic complex nanoparticles, dichloro cobalt(II) bis-benzimidazole (Co-BMZ) and dichloro copper(II) bis-benzimidazole (Cu-BMZ), were synthesized by reprecipitation method and their anti-cancer activity by means of photothermal effect has been studied. Transmission electron microscopy analysis shows that the particle size of Cu-BMZ is ∼100 nm and Co-BMZ is in the range between 100 and 400 nm. Zeta potential analysis ensures the stability of the synthesized nanoparticles. It is found that the nonlinear absorption of the nanoparticles increases with increase in laser power intensity. Phototoxicity of human lung cancer (A549) and the normal mouse embryonic fibroblast (NIH/3T3) cells was studied using a 650 nm laser. Even though both the cell lines were affected by laser irradiation, A549 cells show higher cell destruction and lower IC50 values than the normal cells. Docking studies were used to analyse the interaction site and the results showed that the Cu-BMZ molecules have higher dock score than the Co-BMZ molecules. The obtained results indicate that Cu-BMZ samples have lesser particle size, higher nonlinear absorption and higher interaction energy than the Co-BMZ samples.

Graphical abstract

Carnosine-graphene oxide conjugates decorated with hydroxyapatite as promising nanocarrier for ICG loading with enhanced antibacterial effects in photodynamic therapy against Streptococcus mutans

Publication date: Available online 9 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Elham Gholibegloo, Ashkan Karbasi, Maryam Pourhajibagher, Nasim Chiniforush, Ali Ramazani, Tayebeh Akbari, Abbas Bahador, Mehdi Khoobi
Antimicrobial photodynamic therapy (aPDT) has been emerged as a noninvasive strategy to remove bacterial contaminants such as S. mutans from the tooth surface. Photosensitizer (PS), like indocyanine green (ICG), plays a key role in this technique which mainly suffers from the poor stability and concentration-dependent aggregation. An appropriate nanocarrier (NC) with enhanced antibacterial effects could overcome these limitations and improve the efficiency of ICG as a PS. In this study, various ICG-loaded NCs including graphene oxide (GO), GO-carnosine (Car) and GO-Car/Hydroxyapatite (HAp) were synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Filed Emission Scanning Electron Microscopy (FE-SEM), Energy Dispersive Spectroscopy (EDS), Zeta Potential and Ultraviolet-Visible spectrometry (UV–Vis). The colony forming unit and crystal violet assays were performed to evaluate the antimicrobial and anti-biofilm properties of PSs against S. mutans. The quantitative real-time PCR approach was also applied to determine the expression ratio of the gtfB gene in S. mutans. The zeta potential analysis and UV–Vis spectrometry indicated successful loading of ICG onto/into NCs. GO-Car/HAp showed highest amount of ICG loading (57.52%) and also highest aqueous stability after one week (94%). UV–Vis spectrometry analyses disclosed a red shift from 780 to 800 nm for the characteristic peak of ICG-loaded NCs. In the lack of aPDT, GO-Car@ICG showed the highest decrease in bacterial survival (86.4%) which indicated that Car could significantly promote the antibacterial effect of GO. GO@ICG, GO-Car@ICG and GO-Car/HAp@ICG mediated aPDT, dramatically declined the count of S. mutans strains to 91.2%, 95.5% and 93.2%, respectively (P < 0.05). The GO@ICG, GO-Car@ICG, GO-Car/HAp@ICG significantly suppressed the S. mutans biofilm formation by 51.4%, 63.8%, and 56.8%, respectively (P < 0.05). The expression of gtfB gene was considerably reduced to 6.0, 9.0 and 7.9-fold after aPDT in the presence of GO@ICG, GO-Car@ICG, GO-Car/HAp@ICG, respectively (P < 0.05). It could be concluded that the multi-functionalized GO as a novel nanocarrier could significantly enhance the ICG loading, stability, and improve its inhibitory effects as a photosensitizer in aPDT against S. mutans. These findings might provide opportunity for efficient treatment of local dental infections.

Graphical abstract

The expression and function of galectins in skin physiology and pathology

Abstract

The galectin family comprises β-galactoside-binding proteins widely expressed in many organisms. There are at least 16 family members, which can be classified into three groups based on their carbohydrate-recognition domains. Pleiotropic functions of different galectins in physiological and pathological processes through extracellular or intracellular actions have been revealed. In the skin, galectins are expressed in a variety of cells, including keratinocytes, melanocytes, fibroblasts, dendritic cells, lymphocytes, macrophages, and endothelial cells. Expression of specific galectins is reported to affect cell status, such as activation or death, and regulate the interaction between different cell types or between cells and the extracellular matrix. In vitro cellular studies, in vivo animal studies and studies of human clinical material have revealed the pathophysiologic roles of galectins in the skin. The pathogenesis of diverse non-malignant skin disorders, such as atopic dermatitis, psoriasis, contact dermatitis, and wound healing, as well as skin cancers, such as melanoma, squamous cell carcinoma, basal cell carcinoma, and cutaneous hematologic malignancy can be regulated by different galectins. Revelation of biological roles of galectins in skin may pave the way to future development of galectin-based therapeutic strategies for skin diseases.

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Phosphorus sorption capacity of biochars varies with biochar type and salinity level

Abstract

Biochar is recognized as an effective material for recovering excess nutrients, including phosphorus (P), from aqueous solutions. Practically, that benefits the environment through reducing P losses from biochar-amended soils; however, how salinity influences P sorption by biochar is poorly understood and there has been no direct comparison on P sorption capacity between biochars derived from different feedstock types under non-saline and saline conditions. In this study, biochars derived from wheat straw, hardwood, and willow wood were used to compare P sorption at three levels of electrical conductivity (EC) (0, 4, and 8 dS m⁻¹) to represent a wide range of salinity conditions. Phosphorus sorption by wheat straw and hardwood biochars increased as aqueous solution P concentration increased, with willow wood biochar exhibiting an opposite trend for P sorption. However, the pattern for P sorption became the same as the other biochars after the willow wood biochar was de-ashed with 1 M HCl and 0.05 M HF. Willow wood biochar had the highest P sorption (1.93 mg g⁻¹) followed by hardwood (1.20 mg g⁻¹) and wheat straw biochars (1.06 mg g⁻¹) in a 25 mg L⁻¹ P solution. Although the pH in the equilibrium solution was higher with willow wood biochar (~ 9.5) than with the other two biochars (~ 6.5), solution pH had no or minor effects on P sorption by willow wood biochar. The high sorption rate of P by willow wood biochar could be attributed to the higher concentrations of salt and other elements (i.e., Ca and Mg) in the biochar in comparison to that in wheat straw and hardwood biochars; the EC values were 2.27, 0.53, and 0.27 dS m⁻¹ for willow wood, wheat straw, and hardwood biochars, respectively. A portion of P desorbed from the willow wood biochar; and that desorption increased with the decreasing P concentration in the aqueous solution. Salinity in the aqueous solution influenced P sorption by hardwood and willow wood but not by wheat straw biochar. We conclude that the P sorption capacity of the studied biochars is dependent on the concentration of the soluble element in the biochar, which is dependent on the biochar type, as well as the salinity level in the aqueous solution.

Behaviour and risk assessment of fluopyram and its metabolite in cucumber ( Cucumis sativus ) fruit and in soil

Abstract

A field experiment was conducted to estimate residue persistence of fluopyram and its metabolite benzamide in cucumber fruits and soil and their risk assessment in humans and soil environment. Fluopyram (Kafka, 400 SC) was applied as soil drench twice at the interval of 15 days at the rate of 250 (standard dose) and 500 (double dose) g a.i. ha⁻¹ (active ingredient per hectare). Cucumber fruits were collected at 0 (1 h), 1, 3, 5, 7, 10, 15, 20, 30, 40 and 50 days after second application. Soil samples were collected on 15th day after second application. Drench application resulted in detection of residues on the third day in standard dose at the levels of 0.056 mg kg⁻¹ in cucumber fruit. The residue level increased until 20 days reaching 0.092 mg kg⁻¹ followed by decrease to 0.068 mg kg⁻¹ on 30th day after application. In double dose, the residues started accumulating from 0 day with initial levels of 0.093 mg kg⁻¹ and persisted until 30th day. The levels varied between 0.123 and 0.184 mg kg⁻¹ until 15th day of application followed by decrease to 0.127 mg kg⁻¹ by 30th day. The residues reached below determination level (< 0.05 mg kg⁻¹) on 40th day in both the doses after second application. The residue of metabolite benzamide was below determination level (< 0.05 mg kg⁻¹) at both the doses. Hazard quotient (HQ) for residues levels at 15th and 30th day was less than one (HQ < 1). Hence, a pre-harvest interval of 15 days is suggested. Present data can be used to establish maximum residue limit (MRL) in India. The residue of fluopyram in soil on 15th day and the data on soil adsorption coefficient of fluopyram from literature suggests moderate mobility of fluopyram in soil. However, residues of metabolite of benzamide were not detected in soil. Further studies on translocation of fluopyram in soil over the time can be conducted for better understanding of environmental risk. To our knowledge, this is the first report on residue levels of fluopyram in any crop when applied as soil drench.

Salivary Levels of Angiopoietin 2 in Infants with Infantile Hemangiomas Treated with and without Systemic Propranolol

Abstract

Background

Infantile hemangiomas (IH) with functional or cosmetic concerns necessitate systemictreatment for which propranolol is the preferred treatment. However, the mechanism ofaction is unknown. Mouse models suggest the angiopoietin-2 (Ang2)/Tie-2 system isimplicated. Ang2 can promote endothelial growth or induce apoptosis depending on thepresence of vascular endothelial growth factor (VEGF). This pilot study investigates thesaliva Ang2 levels in infants with IH treated with and without systemic propranolol.

Methods

Patients with clinically confirmed IH were recruited from an academic pediatric.dermatology center. Treatment was based on clinical evaluation. Saliva samples werecollected over six months. An ELISA determined Ang2 levels.

Results

Ang2 levels were detectable in 45% of samples. However, by the late time point only28% had detectable levels. There were no changes of Ang2 over time and there wereno differences in Ang2 levels between groups. However, Ang2 levels were correlatedwith baseline size and changes in size from baseline.

Conclusions

Ang2 is detectable in saliva of affected infants, but does not decrease with propranololtreatment. However, Ang2 levels are positively correlated with size and changes in size.Thus, Ang2 is not the primary factor in the mechanism of propranolol resulting in IHreduction.

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Cryptotanshinone reduces psoriatic epidermal hyperplasia via inhibiting the activation of STAT3

Abstract

The discovery of new therapeutic drugs with the efficacious and safe ability to prevent epidermal hyperplasia is extremely urgent for psoriasis. Cryptotanshinone (CTS), an active component isolated from the root of Salvia miltiorrhiza Bunge, has been reported to have anti-bacterial and anti-tumor effects. However, its effects on psoriasis have not been reported. Here, we investigated the therapeutic effects of CTS on imiquimod (IMQ) induced psoriatic-like skin model and explored the underlying mechanisms. Our results revealed that CTS effectively alleviates IMQ-induced epidermal hyperplasia. In vitro studies also indicated that CTS potently inhibits the growth of keratinocytes. We further found that STAT3, a transcription factor for the cell growth, is the key mediator of CTS on the proliferation of keratinocytes. Taken together, our findings indicated that the curative effects of CTS on psoriasis are accomplished mainly through modulating STAT3, which providing evidences to develop CTS as a potential therapeutic agent for patients with psoriasis.

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Application of an 8% capsaicin patch normalizes epidermal TRPV1 expression but not the decreased intraepidermal nerve fibre density in patients with brachioradial pruritus

Abstract

Background

Topical capsaicin shows efficacy in the treatment of brachioradial pruritus, however its mechanisms of action remain unclear.

Objective

The effect of capsaicin on the epidermis (i.e. peripheral expression of non-neuronal sensory receptors on keratinocytes, morphological changes in innervation) is still unknown. We aimed to investigate the effect of topical capsaicin on keratinocyte expression of TRP channels and on the intraepidermal nerve fibre density (IENFD) in patients with brachioradial pruritus.

Methods

Thirty-one patients with brachioradial pruritus received an 8% capsaicin patch. Biopsies in lesional and non-lesional skin were taken to assess epidermal morphology, keratinocyte expression of TRP channels and IENFD before and 3 weeks after treatment.

Results

Treatment with the capsaicin patch led to a significant decrease in itch and paresthetic symptoms (p<0.05). Keratinocyte morphology is unaltered after capsaicin therapy. Reduced keratinocyte expression of TRPV1 in lesional skin (p=0.009; n=9) normalized three weeks after treatment (p=0.016; n=10), but not the IENFD, which remained reduced in lesional epidermis.

Conclusion

The normalization of the decreased TRPV1 expression may account for the effectiveness of topical capsaicin, which does not reconstitute the reduced IENFD, arguing for a role of epidermal TRPV1 in the maintenance of brachioradial pruritus.

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Distribution of phosphorous pools in western river sediments of the Urmia Lake basin, Iran

Abstract

Impact of anthropogenic loading of phosphorous (P) to an aquatic ecosystem can be qualitatively assessed by measuring the buildup and distribution of P in sediments and by differentiating bioavailable and recalcitrant P pools. Distribution of P pools in sediments is affected by the physico-chemical properties including specific elements, particle size distribution, pH, electrical conductivity (EC), and carbonate content. We applied X-ray fluorescence and scanning electron microscopy (SEM) methods to characterize sediments from western rivers in the Urmia Lake basin in Iran with a particular focus on properties that are relevant to P speciation. Phosphorous pools were sequentially extracted into operationally defined exchangeable (EXCH-P), iron and aluminum oxide-bound (Fe/Al-P), calcium-bound (Ca-P), and residual (RES-P) P pools. In river sediments, the size of P pool was found to be in the order of Ca-P > RES-P > Fe/Al-P > EXCH-P indicating small fraction of bioavailable P pool and Ca-P minerals being the most dominant P sink. Carbonate-related properties had an inverse relationship with bioavailable P pools in the river sediments studied. The principal component analysis (PCA) of the sequential extraction data with sediment properties revealed that four principal components described 82.7% of total variation. Similarly, particle size-related properties were found to have the highest eigenvalues in the first PC. Electron diffraction spectra (EDS) and X-ray fluorescence (XRF) analyses showed a largely uniform distribution of P in the upstream sediment. However, limited evidence of local enrichment of P with Fe, Al, and Ca contents was observed in the downstream river sediments. Correlation of Fe/Al-P pool size with Al₂O₃ and SiO₂ contents indicated that P was associated with Al oxide and clay minerals in the sediment matrix. Overall, the results from this study provide insights into the variability of upstream and downstream river processes and their relationship with P pools with regard to their bioavailability. These results are expected to be useful in assessing the potential impact of P loading on the aquatic ecosystem in the Urmia Lake basin.

Improvement studies on emission and combustion characteristics of DICI engine fuelled with colloidal emulsion of diesel distillate of plastic oil, TiO 2 nanoparticles and water

Abstract

Experimentation was conducted on a single cylinder CI engine using processed colloidal emulsions of TiO₂ nanoparticle-water-diesel distillate of crude plastic diesel oil as test fuel. The test fuel was prepared with plastic diesel oil as the principal constituent by a novel blending technique with an aim to improve the working characteristics. The results obtained by the test fuel from the experiments were compared with that of commercial petro-diesel (CPD) fuel for same engine operating parameters. Plastic oil produced from high density polyethylene plastic waste by pyrolysis was subjected to fractional distillation for separating plastic diesel oil (PDO) that contains diesel range hydrocarbons. The blending process showed a little improvement in the field of fuel oil-water-nanometal oxide colloidal emulsion preparation due to the influence of surfactant in electrostatic stabilization, dielectric potential, and pH of the colloidal medium on the absolute value of zeta potential, a measure of colloidal stability. The engine tests with nano-emulsions of PDO showed an increase in ignition delay (23.43%), and decrease in EGT (6.05%), BSNO_x (7.13%), and BSCO (28.96%) relative to PDO at rated load. Combustion curve profiles, percentage distribution of compounds, and physical and chemical properties of test fuels ascertains these results. The combustion acceleration at diffused combustion phase was evidenced in TiO₂ emulsion fuels under study.

Catalytic oxidation of trichloroethylene from gas streams by perovskite-type catalysts

Abstract

Three perovskite-type catalysts including LaMnO₃, La_0.8Ce_0.2MnO₃, and La_0.8Ce_0.2 Mn_0.8Ni_0.2O₃ are prepared using citric acid sol-gel method and evaluated as catalyst for the oxidation of trichloroethylene (TCE) in air with temperature ranging from 100 to 600 °C. The physicochemical properties of three perovskite-type catalysts were characterized by SEM, EDS, XRD, BET, and XPS to investigate the relationship with catalytic activities. The results show that the removal efficiency of TCE achieved with La_0.8Ce_0.2Mn_0.8Ni_0.2O₃ (the best one) reaches 100% at 400 °C and the mineralization efficiency reaches 100% at 600 °C. The enhanced activity can be attributed to the addition of Ce and Ni which increases the surface areas, active oxygen species, and the redox ability of the Mn⁴⁺/Mn³⁺ ratio on the catalyst surface. As La_0.8Ce_0.2Mn_0.8Ni_0.2O₃ is applied for TCE oxidation, the main intermediate chlorinated byproduct detected is tetrachloroethylene (C₂Cl₄) which is generated by the reaction of TCE and chlorine (Cl₂). The activation energy for the TCE oxidation with La_0.8Ce_0.2Mn_0.8Ni_0.2O₃ catalyst is 51 kJ/mol using kinetic models of power–law type.

Remotely Phototriggered, Transferrin-Targeted Polymeric Nanoparticles for the Treatment of Breast Cancer

Abstract

Triple Negative Breast Cancer (TNBC) has the worst prognosis amongst all sub-types of breast cancer. Currently no targeted treatment has been approved for TNBC. The goal of this study was to design a remotely triggered, targeted therapy for TNBC using polymeric nanoparticles and light. Active targeting of TNBC was achieved by conjugating the nanoparticles to a peptide (hTf) that binds to the transferrin receptor, which is overexpressed in TNBC. Photodynamic Therapy (PDT) was explored for TNBC treatment by remotely triggering benzoporphyrin derivative monoacid (BPD), a photosensitizer, using near infrared light. In this study, we investigated the use of actively targeting polymeric nanoparticles for PDT against TNBC using in vitro imaging and cytotoxicity studies. Fluorescence imaging confirmed that the BPD loaded nanoparticles showed greater fluorescence in TNBC cells compared to free BPD, but more importantly actively targeted nanoparticles displayed stronger fluorescence compared to passively targeted nanoparticles. Moreover, fluorescence imaging following competition with empty targeted nanoparticles validated the specificity of the targeted nanoparticles for TNBC cells. The PDT killing results were in line with the fluorescence imaging results, where actively targeting nanoparticles exhibited the highest phototriggered cytotoxicity in TNBC cells, making them an attractive nanoplatform for TNBC treatment.

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Impact of Adverse Event Solicitation on the Safety Profile of SQ House Dust Mite Sublingual Immunotherapy Tablet

Publication date: Available online 10 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Hendrik Nolte, David I. Bernstein, Gordon L. Sussman, Bodil Svanholm Fogh, Susan Lu, Bernt Husøy, Harold S. Nelson
BackgroundIt has been recommended that sublingual immunotherapy (SLIT) safety be assessed using solicited adverse event (AE) collection methods.ObjectivesTo describe the impact on the safety profile of SQ house dust mite (HDM) SLIT-tablet (12 SQ-HDM dose) when pre-specified local application site reactions were solicited vs unsolicited, and discuss ramifications of AE solicitation.MethodsSubjects were randomized to daily 12 SQ-HDM or placebo for up to 52 weeks in 4 double-blinded, multicenter trials. In one trial (NCT01700192; N=1,272), subjects documented daily the presence or absence of 15 World Allergy Organization-defined local application site reactions using a structured questionnaire of closed-ended questions (solicited AEs). Subjects in the other trials were not asked about specific AEs (unsolicited AEs) and AE data were pooled (N=1,287). Analysis was limited to adults aged 18-65 years.ResultsWhether AEs were solicited or unsolicited, the most common AEs leading to study discontinuation with 12 SQ-HDM were throat irritation and oral pruritus. Approximately 95% of treatment-related AEs were mild-to-moderate. Placebo-subtracted frequencies of local application site reactions associated with 12 SQ-HDM were higher when solicited vs unsolicited (i.e., throat irritation, 46% vs 13%, respectively; oral pruritus, 47% vs 17%; ear pruritus, 40% vs 4%; mouth swelling, 8% vs 2%; tongue ulceration, 10% vs 0%; mouth ulceration, 7% vs <1%).ConclusionsQualitatively, the safety profile of 12 SQ-HDM was similar when AEs were solicited vs unsolicited; hence, solicitation did not alter the safety profile. Higher observed frequencies of local application site reactions with AE solicitation may be partly due to suggestive reporting bias, as observed in placebo-treated subjects.