Isolated dorsoradial capsule injuries of the thumb metacarpophalangeal joint are different from those associated with collateral ligament disruption. Early suspicion of this rare injury is important because, if overlooked, ulnarward subluxation of extensor pollicis longus tendon can develop. Functionally, active thumb extension becomes impaired, and over the long term, a thumb Boutonniere's deformity becomes established. Joint hypermobility/instability may predispose to this injury. The 2 cases presented illustrate this through anatomic differences. At the time of acute injury, 3 presenting clinical features should raise suspicion of dorsoradial capsular rupture: a history of isolated hyperflexion injury to the thumb, stable collateral ligaments on examination, and x-ray evidence of palmar subluxation of the proximal phalanx on the metacarpal. Ulnarward subluxation of the extensor pollicis longus is a delayed sign. Diagnostic imaging, beyond x-ray studies, may not be helpful in defining the injury. Early exploration and repair of this injury give the best long-term outcome. Postrepair, metacarpophalangeal joint range of motion may not be fully restored, but stability and a preinjury level of hand function can usually be reestablished.Πέμπτη 11 Ιανουαρίου 2018
Isolated Dorsoradial Capsular Tear of the Thumb Metacarpophalangeal Joint: Missed Diagnosis and the Management of Delayed Presentation
Isolated dorsoradial capsule injuries of the thumb metacarpophalangeal joint are different from those associated with collateral ligament disruption. Early suspicion of this rare injury is important because, if overlooked, ulnarward subluxation of extensor pollicis longus tendon can develop. Functionally, active thumb extension becomes impaired, and over the long term, a thumb Boutonniere's deformity becomes established. Joint hypermobility/instability may predispose to this injury. The 2 cases presented illustrate this through anatomic differences. At the time of acute injury, 3 presenting clinical features should raise suspicion of dorsoradial capsular rupture: a history of isolated hyperflexion injury to the thumb, stable collateral ligaments on examination, and x-ray evidence of palmar subluxation of the proximal phalanx on the metacarpal. Ulnarward subluxation of the extensor pollicis longus is a delayed sign. Diagnostic imaging, beyond x-ray studies, may not be helpful in defining the injury. Early exploration and repair of this injury give the best long-term outcome. Postrepair, metacarpophalangeal joint range of motion may not be fully restored, but stability and a preinjury level of hand function can usually be reestablished.
Integrated Plastic Surgery Residency Applicant Trends and Comparison With Other Surgical Specialties
Background There has been a relatively rapid increase in the number and size of "integrated" residency programs in plastic surgery (PS) over the past decade. The objective of this study is to evaluate trends of US senior applicants of PS compared with other surgical specialties from 2007 to 2016. Methods Data were obtained from "NRMP: Main Residency Match" and from "NRMP: Charting Outcomes in the Match." Frequencies, percentages, and proportions were calculated for categorical variables. Odds ratios with 95% confidence interval were calculated to evaluate the relationship of Alpha Omega Alpha membership and match success. Results The overall National Resident Matching Program match rate ranged from 93.1% to 95.1%, but rates were lower for surgical specialties, ranging from 74.7% to 86.6% in 2016. From 2008 to 2016, PS had a relatively high growth rate in the number of positions (65.2%) from 2008 to 2016. Matched PS and Otolaryngology applicants routinely had the highest mean United States Medical Licensing Examination Step 1 and Step 2 Clinical Knowledge scores. Alpha Omega Alpha membership has a significant impact on successfully matching into a surgical specialty (PThe Effectiveness of Sternocleidomastoid Flap Versus Superficial Musculoaponeurotic System Flap for the Prevention of Frey Syndrome and Facial Depressed Deformity in Parotid Surgery for Pleomorphic Adenoma
The purpose of this study was to compare 2 types of reconstruction techniques: sternocleidomastoid (SCM) flap and superficial musculoaponeurotic system (SMAS) flap after partial parotidectomy (PP) for preventing Frey syndrome (FS) and concave facial depressed deformity. A total of 99 patients underwent PP for pleomorphic adenoma of the parotid gland. The patients were divided in 2 groups according to the dimension of the tumor: tumors less than 3 cm (group A, 47 patients) and tumors greater than or equal to 3 cm (group B, 52 patients). The patients in the 2 groups were assigned to 3 subgroups: PP without reconstruction (subgroup 1), PP and reconstruction with SMAS flap (subgroup 2), PP, and reconstruction with SCM flap (subgroup 3). In group A, the results of FS subjective symptoms, positivity of Minor starch test, and the median score of cosmetic results assessed with Visual Analogue Scale were as follows: in subgroup 1: 20%, 35%, 6; in subgroup 2: 13.3%, 13,3%, 8; in subgroup 3: 0%, 8.3%, 9. In patients of group B, the results were as follows: 60%, 73.3%, 3 in subgroup 1; 28.5%, 35.7%, 5 in subgroup 2; and 8.6%, 8.6%, 8 in subgroup 3. The study demonstrates a statistical difference (PRadioprotection With Amifostine Enhances Bone Strength and Regeneration and Bony Union in a Rat Model of Mandibular Distraction Osteogenesis
Background Using distraction osteogenesis (DO) to regenerate robust endogenous bone could greatly enhance postoncologic reconstruction of head and neck cancer. However, radiation (XRT) corrosive effects still preclude DO's immense potential. We posit that adjunctive pretreatment with the radioprotectant amifostine (AMF) can optimize wound healing and allow for successful DO with quantifiable enhancements in bony union and strength despite previous surgical bed irradiation. Methods Two groups of murine left hemimandibles were exposed to a human equivalent radiation dosage fractionated over 5 daily doses of 7 Gy. AMF-XRT-DO (n = 30) received AMF before radiation, whereas XRT-DO (n = 22) was untreated. All animals underwent left hemimandibular osteotomy and external fixator placement, followed by distraction to a 5.1-mm gap. Left hemimandibles were harvested and mechanically tested for parameters of strength, yield, and breaking load. Results Radiation-related complications such as severe alopecia were significantly increased in XRT-DO compared with the AMF-treated group (P = 0.001), whereas infection and death were comparable (P = 0.318). Upon dissection, bony defects were grossly visible in XRT-DO distraction gap compared with AMF-XRT-DO, which exhibited significantly more complete unions (P = 0.004). Those results were significantly increased in the specimens prophylactically treated with AMF (yield: 39.41 N vs 21.78 N, P = 0.023; breaking load: 61.74 N vs 34.77 N, P = 0.044; respectively). Conclusions Our study revealed that AMF enhances biomechanical strength, regeneration, and bony union after radiation in a murine model of DO. The use of prophylactic AMF in combination with DO offers the promise of an alternative reconstructive option for patients afflicted with head and neck cancer.A Comparative Study of Lateral Extension Versus Conventional Deltopectoral Flap in Head and Neck Reconstruction After Surgical Extirpation of Tumor
Background We investigated outcomes for nondelayed conventional deltopectoral (CDP) flaps and lateral extension deltopectoral (LEDP) flaps. Material and Methods Fifteen CDP flaps and 17 LEDP flaps were raised in 32 patients. All flaps were nondelayed. The flaps were folded only in the LEDP flap group. Six of 17 LEDP flaps were folded to become bilayered flaps to repair full thickness defects. Flap success rates and complication rates were compared between the CDP flap and LEDP flap groups. Results Success rates were 93.33% in the CDP flap group and 94.12% in the LEDP flap group. Overall complication rates of the transferred flaps were 6.67% and 11.76% for CDP and LEDP flaps, respectively. Flap failure rates were 6.67% and 5.88% with CDP flaps and LEDP flaps, respectively. Conclusions Although the CDP flap is the "aged workhorse" in contemporary head and neck reconstructions, it was shown to be a beneficial regional flap with a dependable pedicle and easy technique. The LEDP flap is of value particularly when used to treat full thickness defects of the head and neck or in cases when higher reach is required.Venous Thromboembolism After Surgical Treatment of Breast Cancer
Background Venous thromboembolism (VTE) remains a serious complication after the surgical treatment of breast cancer. Contemporary guidelines limit VTE chemoprophylaxis to the period of hospitalization. We conducted this study to evaluate the frequency of postdischarge VTE among surgically treated breast cancer patients and identify patient level factors associated with postdischarge VTE. Methods Using Arkansas, Florida, Nebraska, and New York state inpatient databases, we conducted a retrospective cohort study of adult women who underwent surgical treatment for breast cancer between October 1, 2008, and September 30, 2013. The primary outcome was a VTE event within 90 days of discharge. Multivariable logistic regression modeling was used to identify patient factors associated with VTE development. Results The final sample included 52,547 women with most undergoing mastectomy without reconstruction (n = 25,665), followed by mastectomy with implant based reconstruction (n = 16,851), lumpectomy (n = 5319), and mastectomy with autologous reconstruction (n = 4622). There were 395 patients (0.8%) who developed at least 1 VTE. Of the 395 VTEs, 32.9% (n = 130) were identified before discharge, whereas 67.1% were identified within 90 days after discharge. Patients with respiratory disease (adjusted odds ratio [AOR] = 1.56 [1.22–1.98]), hypothyroidism (AOR = 1.31 [1.01–1.70]), a hospital stay of more than 5 days (AOR = 8.07 [5.99–10.89]), previous VTE (AOR = 6.26 [3.95–9.91]), or mastectomy with autologous reconstruction (AOR = 1.50 [1.03–2.19]) more frequently developed postdischarge VTEs. Conclusions Nearly two thirds of all 90-day VTE events after breast cancer surgery occur after discharge. Further research should determine whether a longer course of VTE prophylaxis is warranted among specific populations including those with prolonged hospitalizations, previous VTE, and those undergoing autologous reconstruction.Internal Mammary Vessels’ Impact on Abdominal Skin Perfusion in Free Abdominal Flap Breast Reconstruction
Background: Wound healing problems at the donor site in free abdominal flap breast reconstruction cause significant morbidity to patients. No studies have investigated what impact the use of the internal mammary artery in free abdominal flap breast reconstruction has on abdominal skin perfusion. We hypothesized that harvesting the internal mammary vessels (IMV) has a negative effect on abdominal skin perfusion. Methods: The abdomen and anterior thoracic wall of 17 patients scheduled for secondary free abdominal flap breast reconstruction using IMV was pre-, intra-, and postoperatively examined with dynamic infrared thermography. Qualitative and quantitative analyses of the rate and pattern of recovery in Huger's vascular zones were made with each patient being its own control. Zone III on the side where IMV were used was numbered zone IV. The contralateral zone III was used as reference. Results: Postoperative abdominal skin perfusion in zone IV was always significantly reduced compared with zone III (1-tailed t test, PPrepectoral Implant-Based Breast Reconstruction and Postmastectomy Radiotherapy: Short-Term Outcomes
Background: Prosthetic breast reconstruction in the setting of radiotherapy is associated with poor outcomes. Until recently, prosthetic breast reconstruction was predominantly performed by placing the prosthesis in a subpectoral space. Placement of the prosthesis in a prepectoral space is currently emerging as a simpler, alternative approach to subpectoral placement. The impact of postmastectomy radiotherapy (PMRT) on prepectoral reconstruction has not yet been specifically assessed. This study compared the outcomes of patients who underwent immediate, direct-to-implant, or 2-staged, prepectoral breast reconstruction followed by PMRT with those from patients who did not receive PMRT. Methods: Patients with well-perfused skin flaps and without contraindications, including uncontrolled diabetes-mellitus, previous irradiation, and current tobacco use, were offered the prepectoral approach. Following implant or expander placement, patients underwent planned or unplanned radiotherapy. Complications after each stage of reconstruction were recorded. Results: Thirty-three patients underwent 52 breast reconstructions via the prepectoral approach. Sixty-five percentage of the breasts were irradiated, including 21% after expander and 44% after implant placement. Patients were followed for a mean of 25.1 ± 6.4 months. Complication rate in irradiated breasts was 5.9% (1 incidence of seroma and 1 incidence of wound dehiscence followed by expander removal) and 0% in nonirradiated breasts. Capsular contracture rate was 0% in both irradiated and nonirradiated breasts. Conclusions: Immediate implant-based prepectoral breast reconstruction followed by PMRT appears to be well tolerated, with no excess risk of adverse outcomes, at least in the short term. Longer follow-up is needed to better understand the risk of PMRT in prepectorally reconstructed breasts.
Rbm10 regulates inflammation development via alternative splicing of Dnmt3b
Abstract
RNA-binding motif 10 (Rbm10) is an RNA-binding protein that regulates alternative splicing, but its role in inflammation is not well defined. Here, we show that Rbm10 controls appropriate splicing of DNA (cytosine-5)-methyltransferase 3b (Dnmt3b), a DNA methyltransferase, to regulate the activity of NF-κB-responsive promoters and consequently inflammation development. Rbm10 deficiency suppressed NF-κB-mediated responses in vivo and in vitro. Mechanistic analysis showed that Rbm10 deficiency decreased promoter recruitment of NF-κB, with increased DNA methylation of the promoter regions in NF-κB-responsive genes. Consistently, Rbm10 deficiency increased the expression level of Dnmt3b2, which has enzyme activity, while it decreased the splicing isoform Dnmt3b3, which does not. These two isoforms associated with NF-κB efficiently, and overexpression of enzymatically active Dnmt3b2 suppressed the expression of NF-κB targets, indicating that Rbm10-mediated Dnmt3b2 regulation is important for the induction of NF-κB-mediated transcription. Therefore, Rbm10-dependent Dnmt3b regulation is a possible therapeutic target for various inflammatory diseases.Extensively re-organized systemic lymph nodes provide a feasible environment for self-reactivity in lupus-prone NZB × NZW F1 mice
Abstract
Lymphadenopathy is a frequently observed symptom in systemic lupus erythematosus, although the immunological role of lymph nodes (LNs) in systemic autoimmunity remains largely unknown. Here, we performed comprehensive and systematic analyses of LNs in lupus-prone NZB × NZW F1 (BWF1) mice, demonstrating extensive tissue re-organization of the systemic LNs with follicular expansion, hyper germinal center (GC) formation, atrophy of the paracortical T-cell area and expansion of the medulla in aged BWF1 mice bearing glomerulonephritis. The proportion of B cells was significantly increased in these reactive LNs but not in the spleen, and lymphocyte subsets involved in antibody production, i.e. GC B cells, follicular helper T cells and plasma cells, were elevated. Draining LNs of the affected organs, such as the renal and cervical nodes, showed enhanced tissue re-organization and accumulation of effector lymphocytes, suggesting the presence of a positive feedback loop of regional responses. LN cells isolated from disease-bearing animals produced anti-DNA antibody, indicating activation of autoreactive lymphocytes in situ. The substantial development of disease and LN alterations in mice that received a splenectomy at a young age points to the importance of other secondary lymphoid organs, most likely LNs, for the progression of autoimmune responses independent of the spleen. Taken together, our findings highlight the value of taking LN alterations and activities into consideration for understanding the pathogenesis of systemic autoimmunity.Lysosome biogenesis regulated by the amino-acid transporter SLC15A4 is critical for functional integrity of mast cells
Abstract
Mast cells possess specialized lysosomes, so-called secretory granules, which play a key role not only in allergic responses but also in various immune disorders. The molecular mechanisms that control secretory-granule formation are not fully understood. Solute carrier family member 15A4 (SLC15A4) is a lysosome-resident amino-acid/oligopeptide transporter that is preferentially expressed in hematopoietic lineage cells. Here, we demonstrated that SLC15A4 is required for mast-cell secretory-granule homeostasis, and limits mast-cell functions and inflammatory responses by controlling the mTORC1–TFEB signaling axis. In mouse Slc15a4−/− mast cells, diminished mTORC1 activity increased the expression and nuclear translocation of TFEB, a transcription factor, which caused secretory granules to degranulate more potently. This alteration of TFEB function in mast cells strongly affected the FcεRI-mediated responses and IL-33-triggered inflammatory responses both in vitro and in vivo. Our results reveal a close relationship between SLC15A4 and secretory-granule biogenesis that is critical for the functional integrity of mast cells.Impact of donor and recipient human cytomegalovirus status on kidney transplantation
Abstract
Human cytomegalovirus (HCMV) is considered to be a major pathogen that affects the outcome of solid organ transplantation (TX). Both recipient and donor may be HCMV positive, therefore HCMV re-infection is possible after TX. However, little is known how cytomegalovirus (CMV) transmitted from an infected donor to an infected recipient modulates the recipient's already suppressed immunity, and what the clinical consequences are. To investigate these issues, 52 kidney recipients were followed up for 2 years after TX. T, B and natural killer (NK) lymphocytes, naive and memory T subsets, CD28 expression, relative telomere length, CMV-specific lymphocytes and serum cytokines were measured several times post-TX. Patients were monitored for signs of CMV viremia and other infections. The most important observation was that CMV-specific lymphocytes expand vastly in HCMV-infected recipients who received kidneys from infected donors, in comparison with uninfected donors. Despite this, a higher rate of HCMV viremia was found. Immune deterioration was confirmed by an increased number of CD28-negative T lymphocytes, inverted CD4/CD8 index and shortened telomeres. This was superior in HCMV-infected recipients transplanted from infected donors, when compared with uninfected. In conclusion, CMV alters the immune system in kidney transplant recipients and promotes immune exhaustion.How to optimize aesthetic outcomes in implant-based breast reconstruction.
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How to optimize aesthetic outcomes in implant-based breast reconstruction.
Arch Plast Surg. 2018 Jan 10;:
Authors: Nava MB, Catanuto G, Rocco N
Abstract
The evolution of breast reconstructive surgery keeps pace with the evolution of breast oncologic surgery. The reconstructive choice should always balance the optimal local control of disease and the best cosmetic result, reflecting an informed decision that is shared with the patient, who is always at the center of the decision-making process. Implant-based breast reconstruction following mastectomy represents a complex choice. In order to obtain optimal results, the following considerations are mandatory: thorough preoperative planning, a complete knowledge of the devices that are used, accurately performed surgery, and appropriate follow-up.
PMID: 29316774 [PubMed - as supplied by publisher]
Associations of Bar and Restaurant Smoking Bans With Smoking Behavior in the CARDIA Study: A 25-Year Study
Abstract
Indoor smoking ban policies have often been associated with reductions in smoking prevalence. However, few studies have evaluated their association with within-person changes in smoking behaviors. We linked longitudinal data from 5,105 adults from the Coronary Artery Risk Development in Young Adults study (1985–2011, aged 18–35 at baseline) to state, county, and local 100% smoke-free policies in all bars and restaurants by census tract. We used fixed effects models to examine the association of smoking bans with within-person change in current smoking risk, smoking intensity (smoking ≥10 cigarettes per day on average versus <10) and quit attempts, using both linear and non-linear adjustment for secular trends. In models assuming a linear secular trend, smoking bans were associated with a decline in current smoking risk and smoking intensity and an increased likelihood of a quit attempt. The association with current smoking was greatest among participants with a bachelor's degree or higher. In models with a non-linear secular trend, pooled results were attenuated (confidence intervals included null), but effect modification results were largely unchanged. Findings suggest that smoking ban associations may be difficult to disentangle from other tobacco control interventions, and emphasize the importance of evaluating equity throughout policy implementation.How to review a paper for archives of plastic surgery, communicate as a reviewer, and handle disagreements with authors.
| Related Articles |
How to review a paper for archives of plastic surgery, communicate as a reviewer, and handle disagreements with authors.
Arch Plast Surg. 2018 Jan 10;:
Authors: Kim YH
PMID: 29316775 [PubMed - as supplied by publisher]
Immediate application of vacuum assisted closure dressing over free muscle flaps in the lower extremity does not compromise flap survival and results in decreased flap thickness.
| Related Articles |
Immediate application of vacuum assisted closure dressing over free muscle flaps in the lower extremity does not compromise flap survival and results in decreased flap thickness.
Arch Plast Surg. 2018 Jan 10;:
Authors: Chim H, Zoghbi Y, Nugent AG, Kassira W, Askari M, Salgado CJ
Abstract
Background: Free muscle flaps are a mainstay for reconstruction of distal third leg wounds and for large lower extremity wounds with exposed bone. However a major problem is the significant postoperative flap swelling, which may take months to resolve. We studied the efficacy and safety of immediate application of a vacuum assisted closure (VAC) dressing after a free muscle flap to the lower extremity.
Methods: Over a 19 month period, all consecutive free muscle flaps for lower extremity reconstruction at a Level I trauma center were evaluated prospectively for postoperative flap thickness, complications and flap survival. Immediate application of a VAC dressing was performed in 9 patients, while the flap was left exposed for monitoring in 8 patients.
Results: There was no statistically significant difference in flap survival between both cohorts. Mean flap thickness at postoperative day 5 for the VAC group was 6.4±6.4 mm, while flap thickness for the exposed flap group was 29.6±13.5 mm. Flap thickness was significantly decreased at postoperative day 5 for the VAC dressing group.
Conclusions: Immediate application of VAC dressing following free muscle flaps to the lower extremity does not compromise flap survival or outcomes and results in decreased flap thickness and a better aesthetic outcome.
PMID: 29316773 [PubMed - as supplied by publisher]
Risk factors for delayed healing at the free anterolateral thigh flap donor site.
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Risk factors for delayed healing at the free anterolateral thigh flap donor site.
Arch Plast Surg. 2018 Jan 10;:
Authors: Abe Y, Kashiwagi K, Ishida S, Mineda K, Yamashita Y, Hashimoto I
Abstract
Background: The free anterolateral thigh (ALT) flap has been widely used for various kinds of reconstructions. However, delayed healing at the donor site occasionally occurs due to wound dehiscence or the partial loss of grafted skin at the donor site. The aim of the present study was to identify reliable predictive factors for delayed healing at the donor site after the harvest of a free ALT flap.
Methods: This study included 52 patients who underwent reconstructive procedures using free ALT flaps. The delayed healing group included patients with wounds at the donor site that had not healed over 3 weeks after surgery, and the normal healing group included patients who showed wound healing within 3 weeks after surgery. Multivariate logistic regression models were created to identify the risk factors for delayed healing at the ALT flap donor site.
Results: Among the 52 patients, 24 (46.2%) showed delayed healing at the donor site, and 6 patients required additional operative treatment. A high preoperative body mass index (BMI), smoking, and skin grafting were found to be significantly associated with delayed healing at the ALT donor site. Of the 37 patients who underwent skin grafting, 23 (62%) experienced delayed healing at the donor site.
Conclusions: A high preoperative BMI, smoking, and skin grafting were risk factors for delayed healing at the free ALT donor site. Skin grafting at the ALT donor site should be avoided in patients with a high BMI or a habit of smoking.
PMID: 29316772 [PubMed - as supplied by publisher]
A practical method for accurate coordination between the plastic surgeon and the pathologist: the clockwork technique.
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A practical method for accurate coordination between the plastic surgeon and the pathologist: the clockwork technique.
Arch Plast Surg. 2018 Jan 10;:
Authors: Sezgin B, Kapucu I, Yenidunya G, Bulutay P, Armutlu A, Ozmen S, Yavuzer R
PMID: 29316771 [PubMed - as supplied by publisher]
IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells
Abstract
IL-11 has been detected in inflamed joints; however, its role in the pathogenesis of arthritis is not yet clear. Studies were conducted to characterize the expression and functional significance of IL-11 and IL-11Rα in rheumatoid arthritis (RA). IL-11 levels were elevated in RA synovial fluid (SF) compared to osteoarthritis (OA) SF and plasma from RA, OA and normal individuals (NLs). Morphologic studies established that IL-11 was detected in lining fibroblasts and macrophages in addition to sublining endothelial cells and macrophages at higher levels in RA compared to NL synovial tissues. Since IL-11Rα was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11Rα strongly provoked fibroblast infiltration into RA joint, while cell proliferation was unaffected by this process. Secretion of IL-8 and VEGF from IL-11 activated RA fibroblasts was responsible for the indirect effect of IL-11 on endothelial cell transmigration and tube formation. Moreover, IL-11 blockade impaired RA SF capacity to elicit endothelial cell transmigration and tube formation. We conclude that IL-11 binding to endothelial IL-11Rα can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization.
Epidemiologie des Harnblasenkarzinoms in Deutschland
Zusammenfassung
Der Artikel gibt einen Überblick über Inzidenz‑, Mortalitäts- und Überlebensraten des Harnblasenkarzinoms in Deutschland, beruhend auf den Daten der epidemiologischen Krebsregister sowie der amtlichen Todesursachsenstatistik. Aufgrund der klinischen Relevanz werden auch histologisch nichtinvasive Formen, die fast die Hälfte der jährlich zuletzt knapp 30.000 Neuerkrankungen pro Jahr ausmachen, in die Analysen mit einbezogen, obwohl die nichtinvasiven papillären Karzinome (Ta) ebenso wie die selteneren flachen In-situ-Karzinome (Tis) in der ICD-10 nicht zu den bösartigen Neubildungen gezählt werden. Zusammen mit den T1-Tumoren werden beide Formen klinisch als nichtmuskelinvasive Harnblasenkarzinome zusammengefasst. Histologisch liegen in mindestens 94 % der Fälle Urothelkarzinome vor, andere Formen wie Plattenepithel- und Adenokarzinome sind entsprechend selten. Das mittlere Erkrankungsalter liegt bei knapp 75 Jahren, Männer sind etwa dreimal häufiger betroffen als Frauen. Im Jahr 2015 sind etwa 5700 Menschen in Deutschland an einem Harnblasenkarzinom verstorben. Die altersstandardisierte Sterberaten sind in Deutschland deutlich rückläufig und gehören zu den niedrigsten in der Europäischen Union. Der internationale Vergleich von Inzidenz- und Überlebensraten wird durch unterschiedliche Handhabung und Einbeziehung der nichtinvasiven Karzinome in den Krebsregistern erschwert. Die relativen Überlebensraten in Deutschland sind jedoch gut vergleichbar mit den Ergebnissen aus den US-amerikanischen SEER-Registern und liegen 10 Jahre nach Erstdiagnose für muskelinvasive Tumoren unter 40 %. Deutlich günstiger ist die Prognose bei den nichtmuskelinvasiven Formen mit relativen Zehnjahresüberlebensraten zwischen 63 % und 94 %, je nach Tumorstadium und Differenzierungsgrad. Vor allem bei nichtinvasiven High-grade-Tumoren werden die Überlebenschancen v. a. durch das Risiko der Progression zu muskelinvasiven Stadien bestimmt, das auch nach intensiver Therapie wahrscheinlich noch über viele Jahre erhöht ist.
Ziziphus spina - christi leaf extract pretreatment inhibits liver and spleen injury in a mouse model of sepsis via anti-oxidant and anti-inflammatory effects
Abstract
Sepsis is a systemic response to infection that can result in acute hepatic and splenic damage. Ziziphus spina-christi (L.) is a wild tree used as a medicinal plant by ancient Egyptians. However, little is known about the mechanism underlying its effects on sepsis. The current study investigated the protective effects of a Z. spina-christi leaf extract (ZSCLE) on liver and spleen damage in a male C57BL/6 mouse model of sepsis, induced by cecal ligation and puncture (CLP). Prior to CLP, ZSCLE was administered daily for five consecutive days via oral gavage at doses of 100, 200, or 300 mg/kg. The mice were euthanized 9 h after CLP, and oxidative stress markers were measured (myeloperoxidase, lipid peroxidation, nitric oxide, and reduced glutathione). In addition, we investigated histological changes, anti-oxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), cytokine levels, protein expression of nuclear factor-κB and inducible nitric oxide synthase (iNOS), and mRNA levels of mitogen-activated protein kinase (8, 9, and 14), iNOS, tumor necrosis factor-α, and interleukin-1β. Our results indicated that ZSCLE significantly and dose-dependently inhibited sepsis-induced liver and spleen injury. These results suggest that ZSCLE could provide a therapeutic agent for sepsis by inducing anti-inflammatory and anti-oxidant effects.
Does biochar affect the availability and chemical fractionation of phosphate in soils?
Abstract
Biochar as a soil amendment has been reported to affect the content and availability of soil nutrients. In this study, we aimed to test whether the biochar addition to soils would change the availability and chemical fractionation of phosphate in soils. Two soils (Ultisol and Alfisol) were amended with five kinds of biochars at application rate of 0, 1, and 2% (w/w). After 3-month incubation, availability and chemical forms of P were measured to investigate the potential effect and role of biochar in improving P availability in soils. The biochars used here had a lager variation of P content, depending on their feedstocks. Compared to the untreated soils, application of biochars derived from deciduous tree leaves (DLB), reed (RB), and rice straw (RSB) significantly increased the pH of two soils. The total P content of biochar-amended soils was increased with the addition of biochars. However, only RSB exhibited a significant increase (p < 0.05) of total P content. Application of biochars significantly increased the NH4Cl-extractable P content of two soils, indicating that biochars were able to increase the availability of phosphate in soils, but the amount of available P was dependent on biochar types. Ultisol and Alfisol amended with RSB (2% w/w) showed an increase in the P availability (0.5 M NaHCO3-extractable P) by 46 and 39%, respectively. For strongly acidic Ultisol, addition of biochar significantly increased Al-P and Ca-P content, as well as decreased Fe-P content. The P desorption test indicated the release of P from soils increased with the addition of biochar. Results suggested that biochar would change the P sorption affinity of the soil and help to increase the availability of fixed P. The increase of P availability with biochar application was due to the pH change and direct P contribution from biochar. Our results concluded that biochar affected the availability, chemical forms, and sorption capability of phosphate in soil. The extent of biochar effects on soil P varied greatly with the type of feedstock of biochar and soil type.
Effect of early natal supplementation of paracetamol on attenuation of exotoxin/endotoxin induced pyrexia and precipitation of autistic like features in albino rats
Abstract
The present study was aimed to test the hypothesis that paracetamol (PCM) can precipitate autistic like features when used to counteract vaccine-induced fever using experimental rat pups. The pups were treated with measles mumps rubella (MMR) vaccine, diphtheria tetanus and pertussis (DPT) vaccines and lipopolysaccharide (LPS) with subsequent PCM treatment. The pups were evaluated for postnatal growth (weight gain, eye opening) and behavior alterations (swimming performance, olfactory discrimination, negative geotaxis, nociception, and locomotor activity) by performing battery of neurobehavioral test. Significant correlation was observed between social behavioral domains (nociception, anxiety and motor coordination) and pro-inflammatory load in the pups when treated with MMR/LPS along with PCM. A significant change in pro and anti-inflammatory (IL-4, IL-6, IL-10) markers were observed in rats treated with PCM, MMR, LPS, DPS alone or in combination with MMR, LPS and DPT (5128.6 ± 0.000, 15,488 ± 0.000***, 9661.1 ± 157.29***a, 15,312 ± 249.29*** , 10,471 ± 0.00***a, 16,789 ± 273.34*** and 12,882 ± 0.00***a). Pups were also scrutinized for the markers of oxidative stress, inflammation and histopathologically. All the treatment groups showed significant alteration in the behavioral changes, oxidative markers (TBARS-in control-4.33 ± 0.02, PCM-9.42 ± 0.18***, MMR-5.27 ± 0.15***, MMR + PCM-8.57 ± 0.18*** a, LPS-6.84 ± 0.10***, LPS + PCM-4.51 ± 0.30***a, DPT-5.68 ± 0.12***, DPT + PCM-7.26 ± 0.18***a) and inflammatory markers without following any specific treatment. These observation could be accorded to variable phenotypes of autistic spectrum disorders (ASDs).
Preliminary Psychometric Testing of the Postpartum Depression Predictors Inventory-Revised (PDPI-R) in Portuguese Women
Abstract
Introduction Postpartum depression (PPD) is a prevalent condition with a serious impact. The early identification of women at risk for developing PPD allows for primary prevention and the delivery of timely appropriate referrals. This study investigated the validity and reliability of the postnatal version of the Postpartum Depression Predictors Inventory-Revised (PDPI-R), an instrument widely studied internationally, in Portuguese women. Methods The sample consisted of 204 women who participated in an online cross-sectional survey. Participants completed the European Portuguese versions of the PDPI-R, the Edinburgh Postnatal Depression Scale (EPDS), and the Postnatal Negative Thoughts Questionnaire at 1–2 months postpartum. Additionally, ROC analyses were performed to conduct an exploratory analysis of the instruments' predictive validity. Results The prevalence rates of clinical postpartum depressive symptoms were 27.5 and 14.2% using the cut-off scores of 9 and 12, respectively, on the EPDS. The European Portuguese postnatal version of the PDPI-R demonstrated acceptable reliability and satisfactory construct and convergent validity. When using the EPDS > 9 cut-off score, the exploratory analyses yielded a sensitivity of 76.8% and a specificity of 73.0% with a cut-off score of 5.5 [area under the curve = 0.816]. Discussion These preliminary findings encourage the use of the postnatal version of the PDPI-R as a screening tool to identify Portuguese women at high risk for developing PPD. Subsequent assessments are needed to support the routine application of the PDPI-R both in research and for clinical purposes.
Complete resorption of Veritas® in acellular dermal matrix (ADM)-assisted implant-based breast reconstructions—is there a need for tighter regulation of new products developed for use in breast reconstruction?
Abstract
Background
Veritas® collagen matrix is derived from bovine pericardium and is currently used in soft tissue and breast reconstruction. This study reports the experience of implant-based breast reconstruction using Veritas® collagen matrix in a specialist breast unit.
Methods
This case series included all consecutive patients undergoing mastectomy and implant-based reconstruction using Veritas® over an 18-month period. Demographics, risk factors, operative parameters and postoperative outcomes were recorded prospectively.
Results
Nineteen patients underwent a total of 30 breast reconstruction procedures over the study period. Of these, 57.9% (N = 11) had bilateral procedures. Breast cancer was the commonest indication. Forty percent (N = 12) had concomitant axillary surgery. Forty percent (N = 12) had two-stage reconstruction. Prophylactic antibiotics and drains were used in all cases. Median mastectomy weight was 308 g (interquartile range (IQR) 205–363 g). Median implant volume was 350 ml (IQR 275–400 ml). Twenty percent (N = 6) had minor complications within 3 months. Forty-two percent (N = 8) of patients had complete resorption of Veritas® (50%, N = 15 reconstructions) with "bottoming out" of implants requiring revision surgery. Ten percent (N = 3) developed capsular contracture following radiotherapy and 3.3% (N = 1) had implant loss due to pain following postoperative infection. Product outcomes were reported to the manufacturers.
Conclusions
Veritas® collagen matrix has a comparable immediate postoperative complication rate when compared to other acellular dermal matrix. However, the long-term resorption rate in this series is high resulting in frequent correctional surgery.
Level of Evidence: Level III, risk/prognostic study.
Τετάρτη 10 Ιανουαρίου 2018
Alterations of growth rate and gene expression levels of UPEC by antibiotics at sub-MIC
Abstract
The host is the main environment for bacteria, and they also expose to many antibiotics during the treatment of infectious diseases in host body. In this study, it was aimed to investigate possible changes in growth rate and expression levels of three virulence genes (foc/foc, cnf1, and usp) in a uropathogenic E. coli standard strain within the presence of ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. The UPEC C7 strain was grown on tryptic soy broth-TSB (control), TSB + ciprofloxacin, TSB + nitrofurantoin, and TSB + trimethoprim-sulfamethoxazole for determination of both growth rate and gene expression level. Antibiotics were added according to their sub-minimal inhibition concentrations. E-test was used to determine MIC values of antibiotics. Growth changes were measured in absorbance 600 nm during 24-h period. Total RNA isolations were performed after incubation for 24 h at 37 °C. Gene expression levels were determined by quantitative PCR. Tukey's post hoc test was used for statistical analysis. According to absorbance values, it has been shown that only ciprofloxacin and trimethoprim-sulfamethoxazole have lead significant decrease on growth rate. We also detected statistically significant differences in each gene expression levels for all antibiotics via relative quantification analysis. Fold changes in gene expression was found 0.65, 1.42, 0.23 for foc/foc gene; 0.01, 0.01, 2.84 for cnf1 gene; and 0.1, 0.01, 0.01 for usp gene in the presence of ciprofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole, respectively. This investigation has shown that antibiotics can play a role as an environmental factor which may determine the pathogenicity of bacteria in vivo.
Environmental pollutants, pathogens and immune system in earthworms
Abstract
Earthworms also known as farmer's friends are natural tillers of soil. They belong to Phylum Annelida and class Oligochaeta. Acid soils with organic matter and surface humus maintain the largest fauna of worms and earthworms. Due to their habitat in soil, they are constantly exposed to microbes and pollution generated by anthropogenic sources. Studies have revealed that damage of the immune system of earthworms can lead to alterations of both morphological and cellular characteristics of worms, activation of signalling pathways and can strongly influence their survival. Therefore, the understanding of the robust immune system in earthworms has become very important from the point of view of understanding its role in combating pathogens and pollutants and its role in indicating the soil pollution. In this article, we have outlined the (i) components of the immune system and (ii) their function of immunological responses on exposure to pollutants and pathogens. This study finds importance from the point of view of ecotoxicology and monitoring of earthworm health and exploring the scope of earthworm immune system components as biomarkers of pollutants and environmental toxicity. The future scope of this review remains in understanding the earthworm immunobiology and indicating strong biomarkers for pollution.
Neuroimmunomodulators in neuroborreliosis and Lyme encephalopathy
Abstract
Background
Lyme encephalopathy, characterized by non-specific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to CNS infection. Identical symptoms occur in innumerable other inflammatory states and may reflect the effect of systemic immune mediators on the CNS. Methods
Multiplex immunoassays were used to characterize the inflammatory profile in serum and CSF from Lyme and non-Lyme patients with a range of symptoms to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. Results
CSF CXCL13 was elevated dramatically in confirmed neuroborreliosis (n=8) and to a lesser extent in possible neuroborreliosis (n=11) and other neuroinflammatory conditions (n=44). Patients with Lyme (n=63) or non-Lyme (n=8) encephalopathy had normal CSF findings, but had elevated serum levels of IL-7, TSLP, IL-17A, IL-17F, and MIP-1α/CCL3. Conclusions
CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody (ITAb) production. However, CXCL13 does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory ITAb, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or following appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors. These markers are also elevated in non-Lyme disease patients experiencing similar symptoms. Our results support that in the absence of CSF abnormalities, neurobehavioral symptoms are associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease.Effect of Topical Application of Pure Honey in Chemo-radiation-Induced Mucositis and Its Clinical Benefits in Improving Quality of Life in Patients of Oral Squamous Cell Carcinoma
Abstract
Oral cancer is a major health problem in India, and in certain parts, it represents more than 50% of all cancers. Since almost all of these patients receive chemo-radiotherapy with or without surgery for treatment, a vast majority of them also develop oral mucositis, a debilitating adverse effect of chemo-radiation. There have been various reports in the literature regarding the beneficial role of honey in the management of oral mucositis. The objective of this study was to investigate whether the application of honey in mucositis confers any significant improvement in lesions of mucositis and more specifically whether application of honey brings about any improvement in the quality of life of patients suffering from chemo-radiation-induced oral mucositis. If found to be beneficial, honey could provide a simple, elegant and cost-effective solution to a troublesome health problem, thus benefiting a large number of patients.
Chromium(III) release from chromium-tanned leather elicits allergic contact dermatitis: a use test study
Summary
Background
Chromium (Cr) is a common skin sensitizer. The use of Cr(VI) in leather is restricted in the EU, but that of Cr(III) is not.
Objectives
To assess whether prolonged exposure to Cr-tanned leather with mainly Cr(III) release may elicit allergic contact dermatitis in Cr-allergic individuals.
Method
Ten Cr-allergic subjects and 22 controls were patch tested with serial dilutions of Cr(III) and Cr(VI), and with leather samples. They then conducted a use test with a Cr-tanned and a Cr-free leather bracelet over a period of 3 weeks, for 12 h per day. Cr deposited on the skin from the bracelets was measured in the controls, and the diphenylcarbazide test for Cr(VI) and extraction tests for Cr(III) and Cr(VI) were conducted for the different leathers.
Results
Four of 10 Cr-allergic subjects developed positive reactions to the Cr-tanned bracelet within 7–21 days, whereas only 1 of 10 had a positive patch test reaction to this leather. Cr released from the Cr-tanned leather was most probably entirely Cr(III), with a quantifiable amount being deposited on the skin.
Conclusions
This study strongly suggests that prolonged and repeated exposure to Cr-tanned leather with mainly Cr(III) release is capable of eliciting allergic contact dermatitis in Cr-allergic individuals.
Factors associated with p-phenylenediamine sensitization: data from the Information Network of Departments of Dermatology, 2008–2013
Summary
Background
Risk factors for p-phenylenediamine (PPD) sensitization include the use of hair dyes, the application of temporary black henna tattoos, working as a hairdresser, and, possibly, exposure to hair dye pretests.
Objectives
To quantify the impact of these (putative) risk factors on PPD sensitization.
Methods
Six items related to PPD exposure were added to the routine Information Network of Departments of Dermatology questionnaire from 2008 to 2013. A retrospective analysis of data from 4314 patients tested with PPD 1% pet. was conducted.
Results
Of the PPD-positive patients (n = 271), 80% had their hair dyed, and, of these, 57% subsequently developed scalp dermatitis, whereas only 11% had had a henna tattoo. The self-administrated pretest with hair dye was performed by only a few patients, precluding a more detailed analysis. Hair dyeing [odds ratio (OR) 6.0; 95% confidence interval (CI): 3.9–9.4], henna tattoos (OR 2.4; 95%CI: 1.5–3.7) and being a hairdresser (OR 2.1; 95%CI: 1.3–3.2) increased the risk of PPD sensitization. Neither dyeing of own hair nor application of a temporary henna tattoo seemed to affect PPD sensitization in hairdressers. p-Aminoaryl compounds more often gave positive reactions in patients with henna tattoo.
Conclusions
Hair dyeing is the major risk factor for PPD sensitization in this clinical setting, and application of a temporary black henna tattoo may also lead to (strong) PPD sensitization.
The journey from genetic predisposition to medication overuse headache to its acquisition as sequela of chronic migraine
Migraine remains one of the biggest clinical case to be solved among the non-communicable diseases, second to low back pain for disability caused as reported by the Global Burden of Disease Study 2016. Despite...
Degradation of organics extracted from dewatered sludge by alkaline pretreatment in microbial electrolysis cell
Abstract
Waste activated sludge in China are mostly subjected to dewatering process before final disposal without stabilization. This study investigated the feasibility of organics degradation and H2 production from non-stabilized dewatered sludge (DS) by microbial electrolysis cells (MECs). Alkaline pretreatment was used to disintegrate sludge matrix and solubilize organic matters in DS. Then, the treatment performance of DS supernatant in a single-chamber MEC at various applied voltages was investigated. The COD (chemical oxygen demand) removal rate increased with increasing voltage, which ranged from 26.35 to 44.92% at 0.5–0.9 V. The average coulombic efficiency was 75.6%, while the cathodic hydrogen recovery was not satisfied (15.56–20.05%) with H2 production rates of 0.027–0.038 m3 H2/(m3 day). The reasons could be ascribed to the complexity of the substrate, H2 loss, and the confinement of configuration in scale-up. The organic matter degradation was influenced by the composition of DS. The carbohydrates could be readily used; meanwhile, the major component of the DS supernatant, i.e. proteins, was difficult to be utilized, which resulted from the low biodegradability of the transphilic fractions during the MEC operation.
The Risk of Skin Necrosis Following Hyaluronic Acid Filler Injection in Patients with a History of Cosmetic Rhinoplasty
Abstract
Background
As the number of patients using dermal filler for face augmentation increases, the number of adverse events associated with injection may increase. Unpredictable repositioning of blood vessels and a more tenuous blood supply in the operated nose may increase the risk of ischemia, necrosis and vascular embolism following the filler injection. Objectives
To highlight the importance of the patient's history of previous cosmetic procedures including rhinoplasty in the emergence of vascular complications. Methods
Our medical records over a two-year period were reviewed retrospectively to identify all patients who were treated at our center for vascular complications associated with facial hyaluronic acid filler injections. In each case, the subject's demographic data (gender and age), habitual status, past medical and surgical history, the symptoms and clinical presentation at the first visit, the time interval between the injection and the onset of symptoms, injected filler material and brand, injection sites, the introduced treatment, and photographs were reviewed carefully. Results
A total of seven patients were identified, each developing skin necrosis following injection of the hyaluronic acid filler. All patients reported a cosmetic rhinoplasty more than three years ago. Conclusions
Our finding confirms the conjecture previously made in the literature and suggests that the distinctive vascularity of the nose and the surrounding area may cause filler augmentation induced vascular complications in patients whose vascular circulation has already been compromised by a previous nose surgery.Mild Complications or Unusual Persistence of Porcine Collagen and Hyaluronic Acid Gel Following Periocular Filler Injections
Orbital Extranodal Marginal Zone Lymphoma Following Radiotherapy: A Report of 2 Cases
Purpose: To present 2 patients in whom orbital radiation preceded the development of periorbital extranodal marginal zone lymphoma by more than a decade and to investigate the likelihood of this representing irradiation-induced malignancy. Methods: Retrospective chart review and histopathologic study with immunohistochemistry of 2 cases. Results: The first patient was a 58-year-old woman who developed an orbital mass within the vicinity of the lateral rectus muscle 17 years after external beam proton radiation therapy for an inferotemporal choroidal melanoma. The second patient was a 32-year-old woman who developed a mass in the right lacrimal gland 12 years after external beam photon radiation therapy for chronic inflammatory dacryoadenitis. Histopathologic and immunohistochemical studies confirmed orbital extranodal marginal zone lymphoma in both cases. Retrospective review of older histopathologic slides from the second patient revealed underlying immunoglobulin G4–related disease. Discussion: The unusual sequence of events in these 2 cases raises the question of whether orbital radiation may in rare instances promote the development of orbital extranodal marginal zone lymphoma. The literature pertaining to irradiation-induced secondary malignancy in the orbit is reviewed. Conclusions: Clinicians should consider the possibility of a secondary malignancy when evaluating a patient with an orbital mass and a history of prior local radiation exposure. Accepted for publication November 5, 2017. Natalie Wolkow is supported by a Heed Ophthalmic Fellowship. The remaining authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Frederick A. Jakobiec, M.D., D.Sc., Department of Ophthalmology, David G. Cogan Laboratory of Ophthalmic Pathology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Suite 328, Boston, Massachusetts 02114. E-mail: Fred_Jakobiec@meei.harvard.edu © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.
Significance of Early Postoperative Eyelid Position on Late Postoperative Result in Mueller’s Muscle Conjunctival Resection and External Levator Advancement Surgery
Anomalous Sphenoid Diploe Vein: Case Report Highlighting the Value of Careful CT Evaluation Prior to Decompression Surgery
Lateral bony decompression may offer several biomechanical advantages and has become a commonly used surgical approach. Preoperative imaging plays a key role in surgical planning by providing information about the locoregional anatomy. The marrow space of the greater wing of the sphenoid is a focal point of the decompression surgery based on the volume that it occupies. Several vessels pass through the sphenoid bone, but most are small caliber vessels. The authors describe a case of an uncommon anatomical variant of the cranial diploic venous system in which the anterior transverse diploic vessel traverses the marrow space of the sphenoid. The vessel was identified on preoperative CT evaluation. Despite anticipation of potential bleeding, lateral decompression was abandoned due to difficulties in maintaining hemostasis which compromised the view for safe surgical progress. Accepted for publication November 5, 2017. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Hamzah Mustak, M.D., Stein Eye Institute, University of California Los Angeles, 300 Stein Plaza, Los Angeles, CA 90095. E-mail: shmustak@hotmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.
Removal of cadmium in aqueous solution using wheat straw biochar: effect of minerals and mechanism
Abstract
The biochars were produced from wheat straw (WSBC) at different pyrolytic temperatures. Biochars were characterized by multiple instrumental techniques and were applied to remove Cd from aqueous solution. The removal mechanism was explored, and the quantitative information regarding the relative contribution of related mechanisms to Cd sorption on biochars was provided. The results showed that pseudo-second-order kinetic model, TC (two-compartment) model, and Freundlich isotherm could well fit the process of Cd sorption on biochars. The sorption could be divided into fast and slow adsorption stages. The order of the Cd removal capacity by biochar was WSBC700 > WSBC500 > WSBC300. Adsorption amount of Cd by biochar reduced when the biochar was rinsed with 1.0 M HCl, which indicated that acid-soluble minerals in biochar played an important role during the Cd removal process, especially for the biochar obtained at high pyrolytic temperature. Various equipments were used to investigate the interaction mechanism between biochar and Cd. Mineral precipitation, surface complexation, and cation-π interaction were the main mechanisms of Cd sorption on the biochars. The contribution of cation-π mechanism was in the range of 25.42–48.58%, 2.18–19.30% for surface complexation and 32.12–72.41% for mineral precipitation, respectively. The pyrolytic temperature significantly influenced the removal capacity and mechanism of Cd on biochars. The cation-π mechanism was predominant for biochar obtained at lower pyrolytic temperature. However, mineral precipitation mechanism played a crucial role for biochar obtained at high pyrolytic temperature. These results are helpful for the design or screening of "engineered biochar" to act as sorbents to remove or immobilized Cd in polluted soil or water.
Graphical abstract
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Lead, zinc, and cadmium uptake, accumulation, and phytoremediation by plants growing around Tang-e Douzan lead–zinc mine, Iran
Abstract
In the current study, soils of Tang-e Douzan mine, located in Isfahan, Iran, were collected and analyzed for soluble, exchangeable, and total amounts of Pb, Zn, Cd, Ca, and Mg. The maximum Pb, Zn, Cd, Ca, and Mg concentrations in soils were 2500, 1100, 59, 43,800, and 1320 mg/kg for total metals, 86, 83, 6.3, 4650, and 48 mg/kg for their exchangeable fractions, and 59, 3.7, 0.53, 430, and 6.4 mg/kg for their soluble fractions, respectively. All specimens collected, including 69 plant species, were analyzed for Pb, Zn, and Cd. Moreover, their phytoremediation potential was investigated by calculating bioconcentration factors (BCF), translocation factors (TF), and extraction factors (EF) for each heavy metal. Analysis of the leaves for heavy metals showed no metal hyperaccumulation. The highest shoot concentrations of Pb (298 mg/kg) and Zn (740 mg/kg) were found in Roemeria hybrida subsp. dodecandra and Cd (43 mg/kg) in Chenopodium foliosum. Plants having BCFs and TFs > 1 are capable of phytoextraction. Among the analyzed species, four had both TFs and BCFs > 1 for Zn, 13 for Cd, and none for Pb. R. hybrida, Bromus squarrosus, Descurainia sophia, and Poa bulbosa seem to be the best choices for phytoextraction of Zn. Aegilops columnaris, Allium ampeloprasum subsp. iranicum, B. squarrosus, and Cousinia piptocephala are the best choices for phytoextraction of Cd. Plants with BCF > 1 and TF < 1, including Cerastium dichotomum and Muscari neglectum for Pb, Ceratocephala falcata, M. neglectum, Ornithogalum orthophyllum, and Ranunculus arvensis for Zn and C. falcata, M. neglectum, O. orthophyllum, and R. hybrida subsp. dodecandra for Cd, are proposed to be the most efficient species for metal phytostabilization.
Comment on “Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology Committee”
I read with interest and trepidation "Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology Committee" 1 —interest because at St Jude we invest significant time and expertise in researching and optimizing pediatric neuro-oncologic imaging; trepidation because I was a member of this committee but felt compelled to withdraw because I felt that 2 recommendations were counter to existing evidence and potentially detrimental to patient care.
A change at the helm of Neuro-Oncology
I would like to begin by congratulating our past Editor-in-Chief, Dr. Patrick Wen, for his outstanding work in evolving Neuro-Oncology to increasing heights in quality and impact. Over the past 4 years, under the tutelage and expert leadership of Patrick, Neuro-Oncology has not only thrived, it has exceeded all of our expectations. Patrick has led our journal to an increase in impact factor and has introduced both new features and a sense of enthusiasm and excitement about the journal. The Journal's loss of Patrick is mitigated by the fact that SNO is fortunate to have him as president, and we wish him well in this endeavor, as he continues to participate in helping with the journal.
Reviewer Lists for Neuro-Oncology
The following lists refer to the number of times reviewed within the 12-month period ending October 31, 2017. The names of Editorial Board members and Editorial Team members are excluded from the lists.
Response to Harreld re: “Response assessment in medulloblastoma and leptomeningeal seeding tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology Committee”
What is lost in the letter by Harreld is the mandate of the RAPNO committee and the purpose of the proposed recommendations. Our goal, as a committee, was to develop consensus recommendations on the response assessment for use in clinical trials of patients with medulloblastoma and other seeding tumors, which could then be tested prospectively. Committee recommendations were based on scientific justification where this exists in peer-reviewed literature, or based upon the extensive experience of leaders in the field who are members of this group. Rather than recommend advanced imaging sequences utilized in limited institutions, we proposed recommendations that can be utilized at most institutions and that will allow uniformity and quality data collection. This approach is also in line with the Brain Tumor Drug Development Coalition Imaging Standardization Steering Committee and their recommendations. 1 As such, it required compromise from the committee members in order to be applicable and feasible for the majority of institutions.
Control versus cognition: the changing paradigm of adjuvant therapy for resected brain metastasis
Twenty years ago, Patchell and colleagues1 demonstrated that whole-brain radiotherapy (WBRT) mitigates relapse both in the surgical bed and elsewhere in the brain and prevents death from neurologic causes in patients with resected brain metastasis. Therefore, postoperative WBRT became the standard of care.
The impact of surgery in molecularly defined low-grade glioma: an integrated clinical, radiological, and molecular analysis
Abstract
Background
Extensive resections in low-grade glioma (LGG) are associated with improved overall survival (OS). However, World Health Organization (WHO) classification of gliomas has been completely revised and is now predominantly based on molecular criteria. This requires reevaluation of the impact of surgery in molecularly defined LGG subtypes. Methods
We included 228 adults who underwent surgery since 2003 for a supratentorial LGG. Pre- and postoperative tumor volumes were assessed with semiautomatic software on T2-weighted images. Targeted next-generation sequencing was used to classify samples according to current WHO classification. Impact of postoperative volume on OS, corrected for molecular profile, was assessed using a Cox proportional hazards model. Results
Median follow-up was 5.79 years. In 39 (17.1%) histopathologically classified gliomas, the subtype was revised after molecular analysis. Complete resection was achieved in 35 patients (15.4%), and in 54 patients (23.7%) only small residue (0.1–5.0 cm3) remained. In multivariable analysis, postoperative volume was associated with OS, with a hazard ratio of 1.01 (95% CI: 1.002–1.02; P = 0.016) per cm3 increase in volume. The impact of postoperative volume was particularly strong in isocitrate dehydrogenase (IDH) mutated astrocytoma patients, where even very small postoperative volumes (0.1–5.0 cm) already negatively affected OS. Conclusion
Our data provide the necessary reevaluation of the impact of surgery in molecularly defined LGG and support maximal resection as first-line treatment for molecularly defined LGG. Importantly, in IDH mutated astrocytoma, even small postoperative volumes have negative impact on OS, which argues for a second-look operation in this subtype to remove minor residues if safely possible.Longitudinal assessment of late-onset neurologic conditions in survivors of childhood central nervous system tumors: a Childhood Cancer Survivor Study report
Abstract
Background
Survivors of childhood central nervous system (CNS) tumors experience high rates of treatment-related neurologic sequelae. Whether survivors continue to be at increased risk for new events as they age is unknown. Methods
Adverse neurologic health conditions in 5-year survivors of CNS tumors from the Childhood Cancer Survivor Study (n = 1876) were evaluated longitudinally at a median 23.0 years from diagnosis (range, 5.1–38.9), median age at last evaluation 30.3 years (range, 6.1–56.4). Multivariable regression estimated hazard ratios (HRs) and 95% CIs. Results
From 5 to 30 years post diagnosis, cumulative incidence increased for seizures from 27% to 41%, motor impairment 21% to 35%, and hearing loss 9% to 23%. Risks were elevated compared with siblings (eg, seizures HR: 12.7; 95% CI: 9.6–16.7; motor impairment HR: 7.6; 95% CI: 5.8–9.9; hearing loss HR: 18.4; 95% CI: 13.1–25.9). Regional brain doses of radiation therapy were associated with development of new deficits (eg, frontal ≥50 Gy and motor impairment HR: 2.0; 95% CI: 1.2–3.4). Increased risk for motor impairment was also associated with tumor recurrence (HR: 2.6; 95% CI: 1.8–3.8), development of a meningioma (HR: 2.3; 95% CI: 0.9–5.4), and stroke (HR: 14.9; 95% CI: 10.4–21.4). Seizure risk was doubled by recurrence (HR: 2.3; 95% CI: 1.6–3.2), meningioma (HR: 2.6; 95% CI: 1.1–6.5), and stroke (HR: 2.0; 95% CI: 1.1–3.4). Conclusions
CNS tumor survivors remain at risk for new-onset adverse neurologic events across their lifespans at a rate greater than siblings. Cranial radiation, stroke, tumor recurrence, and development of meningioma were independently associated with late-onset adverse neurologic sequelae.Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location
Abstract
Background
The novel entity of "diffuse midline glioma, H3 K27M-mutant" has been defined in the 2016 revision of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS). Tumors of this entity arise in CNS midline structures of predominantly pediatric patients and are associated with an overall dismal prognosis. They are defined by K27M mutations in H3F3A or HIST1H3B/C, encoding for histone 3 variants H3.3 and H3.1, respectively, which are considered hallmark events driving gliomagenesis. Methods
Here, we characterized 85 centrally reviewed diffuse gliomas on midline locations enrolled in the nationwide pediatric German HIT-HGG registry regarding tumor site, histone 3 mutational status, WHO grade, age, sex, and extent of tumor resection. Results
We found 56 H3.3 K27M-mutant tumors (66%), 6 H3.1 K27M-mutant tumors (7%), and 23 H3-wildtype tumors (27%). H3 K27M-mutant gliomas shared an aggressive clinical course independent of their anatomic location. Multivariate regression analysis confirmed the significant impact of the H3 K27M mutation as the only independent parameter predictive of overall survival (P = 0.009). In H3 K27M-mutant tumors, neither anatomic midline location nor histopathological grading nor extent of tumor resection had an influence on survival. Conclusion
These results substantiate the clinical significance of considering diffuse midline glioma, H3 K27M-mutant, as a distinct entity corresponding to WHO grade IV, carrying a universally fatal prognosis.Inability of positive phase II clinical trials of investigational treatments to subsequently predict positive phase III clinical trials in glioblastoma
Abstract
Background
Glioblastoma is the most common primary malignant brain tumor in adults, but effective therapies are lacking. With the scarcity of positive phase III trials, which are increasing in cost, we examined the ability of positive phase II trials to predict statistically significant improvement in clinical outcomes of phase III trials. Methods
A PubMed search was conducted to identify phase III clinical trials performed in the past 25 years for patients with newly diagnosed or recurrent glioblastoma. Trials were excluded if they did not examine an investigational chemotherapy or agent, if they were stopped early owing to toxicity, if they lacked prior phase II studies, or if a prior phase II study was negative. Results
Seven phase III clinical trials in newly diagnosed glioblastoma and 4 phase III clinical trials in recurrent glioblastoma met the inclusion criteria. Only 1 (9%) phase III study documented an improvement in overall survival and changed the standard of care. Conclusion
The high failure rate of phase III trials demonstrates the urgent need to increase the reliability of phase II trials of treatments for glioblastoma. Strategies such as the use of adaptive trial designs, Bayesian statistics, biomarkers, volumetric imaging, and mathematical modeling warrant testing. Additionally, it is critical to increase our expectations of phase II trials so that positive findings increase the probability that a phase III trial will be successful.Prognostic relevance of genetic alterations in diffuse lower-grade gliomas
Abstract
Background
Diffuse lower-grade gliomas (LGGs) are genetically classified into 3 distinct subtypes based on isocitrate dehydrogenase (IDH) mutation status and codeletion of chromosome 1p and 19q (1p/19q). However, the subtype-specific effects of additional genetic lesions on survival are largely unknown. Methods
Using Cox proportional hazards regression modeling, we investigated the subtype-specific effects of genetic alterations and clinicopathological factors on survival in each LGG subtype, in a Japanese cohort of LGG cases fully genotyped for driver mutations and copy number variations associated with LGGs (n = 308). The results were validated using a dataset from 414 LGG cases available from The Cancer Genome Atlas (TCGA). Results
In Oligodendroglioma, IDH-mutant and 1p/19q codeleted, NOTCH1 mutations (P = 0.0041) and incomplete resection (P = 0.0019) were significantly associated with shorter survival. In Astrocytoma, IDH-mutant, PIK3R1 mutations (P = 0.0014) and altered retinoblastoma pathway genes (RB1, CDKN2A, and CDK4) (P = 0.013) were independent predictors of poor survival. In IDH-wildtype LGGs, co-occurrence of 7p gain, 10q loss, mutation in the TERT promoter (P = 0.024), and grade III histology (P < 0.0001) independently predicted poor survival. IDH-wildtype LGGs without any of these factors were diagnosed at a younger age (P = 0.042), and were less likely to have genetic lesions characteristic of glioblastoma, in comparison with other IDH-wildtype LGGs, suggesting that they likely represented biologically different subtypes. These results were largely confirmed in the cohort of TCGA. Conclusions
Subtype-specific genetic lesions can be used to stratify patients within each LGG subtype. enabling better prognostication and management.Agonist OX40 immunotherapy improves survival in glioma-bearing mice and is complementary with vaccination with irradiated GM-CSF–expressing tumor cells
Abstract
Background
Glioma immunotherapy is an active area of clinical investigation. Glioma-associated immunosuppression remains an obstacle to efficacious immunotherapy, and combination approaches are likely necessary for durable success. OX40 is a member of the tumor necrosis factor receptor superfamily that is upregulated on activated lymphocytes, ligation of which results in enhanced activity and may be active against cancer. We sought to confirm the efficacy of agonist anti-OX40 immunotherapy against glioma and hypothesized that it is complementary with irradiated whole tumor cell vaccination. Methods
GL261 tumor cells were implanted into the right frontal lobes of syngeneic mice, which were then treated with controls, agonist anti-OX40 monoclonal antibody, vaccination with subcutaneous injection of irradiated granulocyte macrophage colony stimulating factor (GM-CSF)–expressing GL261 cells (GVAX), or vaccination + agonist anti-OX40 therapy. Animals were followed for survival. On day 18, splenocytes were harvested for enzyme-linked immunosorbent spot analyses and brains were harvested for immunohistochemistry and flow cytometry analyses of infiltrating lymphocytes. Results
Combination immunotherapy with GVAX and systemic agonist anti-OX40 monoclonal antibody improved survival by 14 days over controls (median survival 36 vs 22 days, P < 0.00005). Systemically, T helper cell type 1 (Th1) antitumor immunity was enhanced significantly by combination therapy. In the brain, combination immunotherapy increased the percentage of Th1 CD4+ T lymphocytes and reduced the fraction that were Th2. In the brain, vaccination improved the ratio of CD8+ to FoxP3+ T lymphocytes, while combination immunotherapy reversed intracranial T-lymphocyte exhaustion, reducing their coexpression of programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) as well as PD-1 and lymphocyte-activation gene 3 (LAG-3). Conclusions
Anti-OX40 immunotherapy is active against intracranial glioma and synergizes with GVAX. Vaccination and anti-OX40 immunotherapy are mechanistically complementary, particularly in the glioma microenvironment.Dissecting human gliomas by single-cell RNA sequencing
Abstract
Diffuse gliomas are the most common human primary brain tumors and remain incurable. They are complex entities in which diverse genetic and nongenetic effects determine tumor biology and clinical course. Our current understanding of gliomas in patients is primarily based on genomic and transcriptomic methods that have profiled them as bulk, providing critical information yet masking the diversity of cells within each tumor. Recent advances in single-cell DNA and RNA profiling have paved the way to studying tumors at cellular resolution. Here, we review initial studies deploying single-cell analysis in clinical glioma samples, with a focus on RNA expression profiling. We highlight how these studies provide new insights into glioma biology, tumor heterogeneity, cancer cell lineages, cancer stem cell programs, the tumor microenvironment, and glioma classification.Activation of WEE1 confers resistance to PI3K inhibition in glioblastoma
Abstract
Background
Oncogenic activation of phosphatidylinositol-3 kinase (PI3K) signaling plays a pivotal role in the development of glioblastoma (GBM). However, pharmacological inhibition of PI3K has so far not been therapeutically successful due to adaptive resistance through a rapid rewiring of cancer cell signaling. Here we identified that WEE1 is activated after transient exposure to PI3K inhibition and confers resistance to PI3K inhibition in GBM. Methods
Patient-derived glioma-initiating cells and established GBM cells were treated with PI3K inhibitor or WEE1 inhibitor alone or in combination, and cell proliferation was evaluated by CellTiter-Blue assay. Cell apoptosis was analyzed by TUNEL, annexin V staining, and blotting of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase. Both subcutaneous xenograft and orthotropic xenograft studies were conducted to evaluate the effects of the combination on tumorigenesis; the tumor growth was monitored by bioluminescence imaging, and tumor tissue was analyzed by immunohistochemistry to validate signaling changes. Results
PI3K inhibition activates WEE1 kinase, which in turn phosphorylates cell division control protein 2 homolog (Cdc2) at Tyr15 and inhibits Cdc2 activity, leading to G2/M arrest in a p53-independent manner. WEE1 inhibition abrogated the G2/M arrest and propelled cells to prematurely enter into mitosis and consequent cell death through mitotic catastrophe and apoptosis. Additionally, combination treatment significantly suppressed tumor growth in a subcutaneous model but not in an intracranial model due to limited blood–brain barrier penetration. Conclusions
Our findings highlight WEE1 as an adaptive resistant gene activated after PI3K inhibition, and inhibition of WEE1 potentiated the effectiveness of PI3K targeted inhibition, suggesting that a combinational inhibition of WEE1 and PI3K might allow successful targeted therapy in GBM.CD70, a novel target of CAR T-cell therapy for gliomas
Abstract
Background
Cancer immunotherapy represents a promising treatment approach for malignant gliomas but is hampered by the limited number of ubiquitously expressed tumor antigens and the profoundly immunosuppressive tumor microenvironment. We identified cluster of differentiation (CD)70 as a novel immunosuppressive ligand and glioma target. Methods
Normal tissues derived from 52 different organs and primary and recurrent low-grade gliomas (LGGs) and glioblastomas (GBMs) were thoroughly evaluated for CD70 gene and protein expression. The association between CD70 and patients' overall survival and its impact on T-cell death was also evaluated. Human and mouse CD70-specific chimeric antigen receptors (CARs) were tested respectively against human primary GBMs and murine glioma lines. The antitumor efficacies of these CARs were also examined in orthotopic xenograft and syngeneic models. Results
CD70 was not detected in peripheral and brain normal tissues but was constitutively overexpressed by isocitrate dehydrogenase (IDH) wild-type primary LGGs and GBMs in the mesenchymal subgroup and recurrent tumors. CD70 was also associated with poor survival in these subgroups, which may link to its direct involvement in glioma chemokine productions and selective induction of CD8+ T-cell death. To explore the potential for therapeutic targeting of this newly identified immunosuppressive axis in GBM tumors, we demonstrate that both human and mouse CD70-specific CAR T cells recognize primary CD70+ GBM tumors in vitro and mediate the regression of established GBM in xenograft and syngeneic models without illicit effect. Conclusion
These studies identify a previously uncharacterized and ubiquitously expressed immunosuppressive ligand CD70 in GBMs that also holds potential for serving as a novel CAR target for cancer immunotherapy in gliomas.Neurological complications of new chemotherapy agents
Abstract
This last decade has yielded more robust development of cancer treatments and first-in-class agents than ever before. Since 2006, nearly one hundred new drugs have received regulatory approval for the treatment of hematological and solid organ neoplasms. Moreover, older conventional therapies have received approval for new clinical indications and are being used in combination with these newer small-molecule targeted treatments. The nervous system is vulnerable to many of the traditional cancer therapies, manifesting both already well-described acute and chronic toxicities. However, newer agents may produce toxicities that may seem indistinguishable from the underlying cancer. Early recognition of neurotoxicities from new therapeutics is vital to avoid irreversible neurological injury. This review focuses on cancer therapies in use in the last 10 years and approved by the FDA from January 2006 through January 1, 2017.MerTK as a therapeutic target in glioblastoma
Abstract
Background
Glioma-associated macrophages and microglia (GAMs) are components of the glioblastoma (GBM) microenvironment that express MerTK, a receptor tyrosine kinase that triggers efferocytosis and can suppress innate immune responses. The aim of the study was to define MerTK as a therapeutic target using an orally bioavailable inhibitor, UNC2025. Methods
We examined MerTK expression in tumor cells and macrophages in matched patient GBM samples by double-label immunohistochemistry. UNC2025-induced MerTK inhibition was studied in vitro and in vivo. Results
MerTK/CD68+ macrophages increased in recurrent tumors while MerTK/glial fibrillary acidic protein–positive tumor cells did not. Pharmacokinetic studies showed high tumor exposures of UNC2025 in a syngeneic orthotopic allograft mouse GBM model. The same model mice were randomized to receive vehicle, daily UNC2025, fractionated external beam radiotherapy (XRT), or UNC2025/XRT. Although median survival (21, 22, 35, and 35 days, respectively) was equivalent with or without UNC2025, bioluminescence imaging (BLI) showed significant growth delay with XRT/UNC2025 treatment and complete responses in 19%. The responders remained alive for 60 days and showed regression to 1%–10% of pretreatment BLI tumor burden; 5 of 6 were tumor free by histology. In contrast, only 2% of 98 GBM mice of the same model treated with XRT survived 50 days and none survived 60 days. UNC2025 also reduced CD206+ macrophages in mouse tumor samples. Conclusions
These results suggest that MerTK inhibition combined with XRT has a therapeutic effect in a subset of GBM. Further mechanistic studies are warranted.Feet in danger: short exposure to contaminated soil causing health damage—an experimental study
Abstract
In this study, hematological and behavioral changes in Wistar rats exposed to soil collected from urban areas next to an industrial complex were investigated. Animals were exposed to soil samples placed at the bottom of cages for 4 days. After this period, behavioral parameters were measured by the open field test and the elevated plus-maze. Blood was collected to measure hematological parameters. The soil from the vicinity of the oil refining industry caused changes in hematological parameters and altered behavioral parameters in both tests. The soil from the vicinity of the petroleum refining industry and fertilizer industries increased the density of white blood cells and decreased exploratory activity in the exposed animals. The results demonstrate that contact with contaminated soils, even for short periods, can cause physiological damage in organisms and that special attention should be given to people who live under constant exposure to these soils.
Contribution of ammonia-oxidizing archaea and ammonia-oxidizing bacteria to ammonia oxidation in two nitrifying reactors
Abstract
In this study, two laboratory nitrifying reactors (NRI and NRII), which were seeded by sludge from different sources and operated under different operating conditions, were found to possess distinct dominant ammonia-oxidizing microorganisms. Ammonia-oxidizing archaeal (AOA) amoA genes outnumbered ammonia-oxidizing bacterial (AOB) amoA genes in reactor NRI, while only AOB amoA genes were detectable in reactor NRII. The AOA amoA gene sequences retrieved from NRI were characterized within the Nitrososphaera sister cluster of the group 1.1b Thaumarchaeota. Two inhibitors for ammonia oxidation, allylthiourea (ATU) and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), were applied individually and as a mixture to observe the ammonia-oxidizing activity of both microorganisms in the reactors' sludge. The results indicated that AOA and AOB jointly oxidized ammonia in NRI, while AOB played the main role in ammonia oxidation in NRII. DNA-stable isotope probing with labeled 13C–HCO3− was performed on NRI sludge. Incorporation of 13C into AOA and AOB implied that both microorganisms may perform autotrophy during ammonia oxidation. Taken together, the results from this study provide direct evidence demonstrating the contribution of AOA and AOB to ammonia oxidation in the nitrifying reactors.
Effect of inorganic and organic solutes on zero-valent aluminum-activated hydrogen peroxide and persulfate oxidation of bisphenol A
Abstract
The effect of varying inorganic (chloride, nitrate, sulfate, and phosphate) and organic (represented by humic acid) solutes on the removal of aqueous micropollutant bisphenol A (BPA; 8.8 μM; 2 mg/L) with the oxidizing agents hydrogen peroxide (HP; 0.25 mM) and persulfate (PS; 0.25 mM) activated using zero-valent aluminum (ZVA) nanoparticles (1 g/L) was investigated at a pH of 3. In the absence of the solutes, the PS/ZVA treatment system was superior to the HP/ZVA system in terms of BPA removal rates and kinetics. Further, the HP/ZVA process was not affected by nitrate (50 mg/L) addition, whereas chloride (250 mg/L) exhibited no effect on the PS/ZVA process. The negative effect of inorganic anions on BPA removal generally speaking increased with increasing charge in the following order: NO3− (no inhibition) < Cl− (250 mg/L) = SO42− < PO43− for HP/ZVA and Cl− (250 mg/L; no inhibition) < NO3− < SO42− < PO43− for PS/ZVA. Upon addition of 20 mg/L humic acid representing natural organic matter, BPA removals decreased from 72 and 100% in the absence of solutes to 24 and 57% for HP/ZVA and PS/ZVA treatments, respectively. The solute mixture containing all inorganic and organic solutes together partly suppressed the inhibitory effects of phosphate and humic acid on BPA removals decreasing to 46 and 43% after HP/ZVA and PS/ZVA treatments, respectively. Dissolved organic carbon removals were obtained in the range of 30 and 47% (the HP/ZVA process), as well as 47 and 57% (the PS/ZVA process) for the experiments in the presence of 20 mg/L humic acid and solute mixture, respectively. The relative Vibrio fischeri photoluminescence inhibition decreased particularly for the PS/ZVA treatment system, which exhibited a higher treatment performance than the HP/ZVA treatment system.
The Bow and Arrow and Early Human Sociality: an Enactive Perspective on Communities and Technical Practice in the Middle Stone Age
Abstract
In this paper, I draw on postphenomenology and material engagement theory to consider the material and emergent character of sociality in Homo faber. I approach this through the context of the bow and arrow, which is a technology that has received recent attention in cognitive archeology as a proxy for assessing criteria that made early human cognition distinct from that of other hominins. Through an ethnographic case study, I scrutinize the forms of knowledge that are required to use the technology in the dynamic field of environmental practices that constitute the hunt. I demonstrate that the learning of the skill is a transformational process where beginners develop self and intentionality by attuning subjective capacities for sensory awareness and creative responsiveness. Through mutual participation, the bow and arrow aligns disposition and rapport among those whose life processes are shaped by the skill. As a mechanism of shared experience, the bow and arrow generates a community can together perceive and act creatively in an impermanent world. Through these observations, I argue that early human sociality was built not on a pre-evolved capacity for symbolic representation but on technical experience, and I consider important questions this raises about the nature of evolutionary processes at work in the development of communities through time.
Commiserating with Devastated Things: Milan Kundera and the Entitlement of Thinking
Commiserating with Devastated Things: Milan Kundera and the Entitlement of ThinkingWIRTHJASON M.fordham university press. 2016. pp. 227227. £54.00. (hbk).
Management of Morgellons Disease With Low-Dose Trifluoperazine
This medical record review examines the novel use of low-dose trifluoperazine, a high-potency typical antipsychotic, in a cohort of patients with Morgellons disease.
Diagnosis of Neurofibromatosis Type 2 From Congenital Skin Plaques
This genetic testing study reports a case of an early diagnosis of neurofibromatosis type 2 (NF2) in a child after genetic analysis of congenital skin plaques, with confirmation of these findings by analysis of skin plaques from 6 unrelated patients with NF2.
Intertriginous Condyloma-like Plaques and Ulcers
A woman in her 50s with a medical history of hypertension and depression was evaluated by the inpatient dermatology consult service for a 1.5-year history of painful intertriginous wounds; she was previously diagnosed with hidradenitis suppurativa. What is your diagnosis?
Human Herpesvirus 8–Associated Inflammatory Cytokine Syndrome
This case report describes a patient with human herpesvirus 8–associated inflammatory cytokine syndrome.
Comorbidity Development in Children With Psoriasis
This cohort study examines the risk ocomorbidities in children with and without psoriasis, after accounting for obesity.
Restoring Serotonergic Homeostasis in the Lateral Hypothalamus Rescues Sleep Disturbances Induced by Early-Life Obesity
Early-life obesity predisposes to obesity in adulthood, a condition with broad medical implications including sleep disorders, which can exacerbate metabolic disturbances and disrupt cognitive and affective behaviors. In this study, we examined the long-term impact of transient peripubertal diet-induced obesity (ppDIO, induced between 4 and 10 weeks of age) on sleep–wake behavior in male mice. EEG and EMG recordings revealed that ppDIO increases sleep during the active phase but reduces resting-phase sleep quality. This impaired sleep phenotype persisted for up to 1 year, although animals were returned to a non-obesiogenic diet from postnatal week 11 onwards. To better understand the mechanisms responsible for the ppDIO-induced alterations in sleep, we focused on the lateral hypothalamus (LH). Mice exposed to ppDIO did not show altered mRNA expression levels of orexin and melanin-concentrating hormone, two peptides that are important for sleep–wake behavior and food intake. Conversely, the LH of ppDIO-exposed mice had reduced contents of serotonin (5-hydroxytryptamine, 5-HT), a neurotransmitter involved in both sleep–wake and satiety regulation. Interestingly, an acute peripheral injection of the satiety-signaling peptide YY 3–36 increased 5-HT turnover in the LH and ameliorated the ppDIO-induced sleep disturbances, suggesting the therapeutic potential of this peptide. These findings provide new insights into how sleep–wake behavior is programmed during early life and how peripheral and central signals are integrated to coordinate sleep.
SIGNIFICANCE STATEMENT Adult physiology and behavior are strongly influenced by dynamic reorganization of the brain during puberty. The present work shows that obesity during puberty leads to persistently dysregulated patterns of sleep and wakefulness by blunting serotonergic signaling in the lateral hypothalamus. It also shows that pharmacological mimicry of satiety with peptide YY3–36 can reverse this neurochemical imbalance and acutely restore sleep composition. These findings add insight into how innate behaviors such as feeding and sleep are integrated and suggest a novel mechanism through which diet-induced obesity during puberty imposes its long-lasting effects on sleep–wake behavior.
A Critical Role for Dopamine D5 Receptors in Pain Chronicity in Male Mice
Dopaminergic modulation of spinal cord plasticity has long been recognized, but circuits affected by this system and the precise receptor subtypes involved in this modulation have not been defined. Dopaminergic modulation from the A11 nucleus of the hypothalamus contributes to plasticity in a model of chronic pain called hyperalgesic priming. Here we tested the hypothesis that the key receptor subtype mediating this effect is the D5 receptor (D5R). We find that a spinally directed lesion of dopaminergic neurons reverses hyperalgesic priming in both sexes and that a D1/D5 antagonist transiently inhibits neuropathic pain. We used mice lacking D5Rs (DRD5KO mice) to show that carrageenan, interleukin 6, as well as BDNF-induced hyperalgesia and priming are reduced specifically in male mice. These male DRD5KO mice also show reduced formalin pain responses and decreased heat pain. To characterize the subtypes of dorsal horn neurons engaged by dopamine signaling in the hyperalgesic priming model, we used c-fos labeling. We find that a mixed D1/D5 agonist given spinally to primed mice activates a subset of neurons in lamina III and IV of the dorsal horn that coexpress PAX2, a transcription factor for GABAergic interneurons. In line with this, we show that gabazine, a GABA-A receptor antagonist, is antihyperalgesic in primed mice exposed to spinal administration of a D1/D5 agonist. Therefore, the D5R, in males, and the D1R, in females, exert a powerful influence over spinal cord circuitry in pathological pain likely via modulation of deep dorsal horn GABAergic neurons.
SIGNIFICANCE STATEMENT Pain is the most prominent reason why people seek medical attention, and chronic pain incidence worldwide has been estimated to be as high as 33%. This study provides new insight into how descending dopamine controls pathological pain states. Our work demonstrates that dopaminergic spinal projections are necessary for the maintenance of a chronic pain state in both sexes; however, D5 receptors seem to play a critical role in males whereas females rely more heavily on D1 receptors, an effect that could be explained by sexual dimorphisms in receptor expression levels. Collectively, our work provides new insights into how the dopaminergic system interacts with spinal circuits to promote pain plasticity.
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