The Epidemic of Guns

The shooting in Las Vegas, Nevada, that left 59 people dead, 10 times that number wounded, and thousands of people with the psychological distress from being present at the scene during and after the massacre has once again raised the issue of what we as a nation can and should do about guns. The solution lies in not just focusing on Las Vegas and the hundreds of other mass shootings that have occurred in the United States in the last 14 months, but rather to underscore that on average almost 100 people die each day in the United States from gun violence. The 36 252 deaths from firearms in the United States in 2015 exceeded the number of deaths from motor vehicle traffic crashes that year (36 161). That same year, the US Centers for Disease Control and Prevention reported that 5 people died from terrorism. Since 1968, more individuals in the United States have died from gun violence than in battle during all the wars the country has fought since its inception.

Anesthesia Duration and Head and Neck Microvascular Reconstruction Complications

This study examines the association of anesthesia duration with complications after microvascular reconstruction of the head and neck.

Combining Rhinoplasty With Upper Lip–Lift Using a Single Incision Line

This Surgical Pearl describes a procedure that combines the columellar incision with the incision for the upper lip–lift, resulting in harmonious nasolabial proportions and a smaller surgical scar.

Outcomes of Buccinator Treatment With Botulinum Toxin in Facial Synkinesis

This cohort study evaluates outcomes for patients treated with botulinum toxin applied to the buccinator muscle in the setting of facial synkinesis.

Botulinum Neuromodulators in Facial Synkinesis Management

This randomized clinical trial evaluates the effectiveness of 3 commercially available botulinum toxin neuromodulators in the treatment of facial synkinesis.

THE NON-NEURONAL AND NON-MUSCULAR EFFECTS OF BOTULINUM TOXIN: A Graceful Opportunity for a Deadly Molecule to Treat a Human Disease in the Skin and Beyond

Abstract

There is growing evidence that botulinum neurotoxins (BoNTs) exhibit biological effects on various human cell types with a host of associated clinical implications. The BoNT receptors and intracellular targets are not unique for neurotransmission. They have been found in both neuronal and non-neuronal cells, but there are differences in the way BoNT binds to, and acts on neuronal vs. non-neuronal cells. The non-neuronal cells expressing one or more BoNT/A-binding proteins and/or cleavage target SNAP-25 include epidermal keratinocytes, mesenchymal stem cells from subcutaneous adipose, nasal mucosal cells, urothelial cells, intestinal epithelial cells, neutrophils, macrophages, and prostate, breast and alveolar epithelial cells, BoNT/A can also elicit specific biological effects in dermal fibroblasts, sebocytes and vascular endothelial cells. The reported non-traditional applications of BoNT in dermatologic conditions include hyperhidrosis, Hailey-Hailey disease, Darier disease, inversed psoriasis, aquagenic palmoplantar keratoderma, pachyonychia congenita, multiple eccrine hydrocystomas, eccrine angiomatous hamartoma, eccrine sweat gland nevi, congenital eccrine nevus, Raynaud phenomenon and cutaneous leiomyomas. Experimental studies demonstrated BoNT/A ability to protect skin flaps, facilitate wound healing, decrease thicknesses of hypertrophic scars, produce an anti-aging effect, and improve a mouse model of psoriasiform dermatitis. Furthermore, experimental studies also have revealed extracutaneous effects of BoNT arising from its anti-inflammatory and anti-cancer properties. Therefore, it is clear that BoNTs have a much wider zone of influence than originally understood, and that these ubiquitous events are based on individual cellular responses to the cholinergic impacts of BoNTs, which represents fertile grounds for future studies that are highly likely to result in impactful discoveries.

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Incentivized goodness

Abstract

It will be argued that humans have a rational self-interest in voluntarily opting to subject themselves to moral bioenhancement. This interest is based on the fact that goodness appears to be conducive to happiness. Those who understand that will be more inclined to opt for safe and effective moral bioenhancement technologies that have the potential to augment our motivation to become better. The more people decide to follow this path, the likelier it is that states will adopt suitable policies that incentivize moral bioenhancement. Hence, goodness, happiness and state incentivized moral bioenhancement can operate in a circularly supportive fashion.

Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma Presenting with Vaginal Sloughing and Ulcerated Skin Nodule

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma (NHL) with subtypes that can be distinguished on the basis of clinical, immunophenotypic, morphologic, and molecular characteristics. The genital tract as a primary site for NHL is very rare (1).

High calcium enhances the expression of double-stranded RNA sensors and antiviral activity in epidermal keratinocytes

Abstract

Double-stranded RNA (dsRNA) sensors including TLR3, MDA5, and RIG-I are expressed in epidermal keratinocytes, and play an important immunological role by enhancing various innate and adaptive immune responses. Although the role of elevated extracellular calcium concentration in keratinocyte differentiation is well understood, the effect of high calcium on dsRNA sensors is not well studied.

We investigated alterations in dsRNA sensor expression and antiviral activity induced by a high extracellular concentration of calcium in epidermal keratinocytes. Normal human epidermal keratinocytes (NHEKs) were stimulated with high calcium and/or synthetic dsRNA, poly (I:C). TLR3, IFIH1 (MDA5), and DDX58 (RIG-I) expression were measured via qPCR, and IFN-β and human beta defensin 2 (HBD2) levels were measured using ELISA. TLR3 localization was evaluated with immunocytofluorescence. Antiviral activity was quantified with virus plaque assays using herpes simplex virus type-1 (HSV-1). High calcium significantly upregulated mRNA expression of TLR3, IFIH1, and DDX58 in NHEKs. In addition, high calcium significantly enhanced poly (I:C)-induced anti-HSV-1 activity in NHEKs. The anti-viral molecule, HBD2 but not IFN-β induction by poly (I:C) was enhanced by high calcium.

Our findings indicate that high levels of extracellular calcium enhance the expression of dsRNA sensors and augment antiviral activity in epidermal keratinocytes.

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Development of an asporogenic Bacillus cereus strain to improve keratinase production in exponential phase by switching sigmaH on and sigmaF off

Abstract

Many bacteria, including the genus Bacillus are able to produce proteases (keratinase). In Bacillus, proteases are produced in the stationary phase and initial stages of sporulation. Protease production is coordinated with sporulation in which expression of various genes by different sigma factors manages the transition from exponential to the stationary phase. In the present study the sigma-F gene of an indigenous Bacillus cereus strain, which is involved in transcription of maintaining sporulation genes was deleted. Meanwhil the sigma-H, which its product activates the genes that function in the zero phase of sporulation and inhibits suppression of protease production, and spo0B genes were expressed in the exponential phase under the control of a sucrose inducible promoter from Bacillus sacPA operon. For the first time, an asporogenic strain of B. cereus was generated that produced higher keratinase (390 U in compare to the 198 U of wild strain) and protease (450 U in compare to the 290 U of wild strain) activities in the exponential growth phase by induction with sucrose. The new strain is promising for production of keratinase for degradation of feather waste to produce feather meal for poultry feed and decrease environmental pollution of poultry industry.

Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC)

Several data indicate that migraine, especially migraine with aura, is associated with an increased risk of ischemic stroke and other vascular events. Of concern is whether the risk of ischemic stroke in migra...

Immunohistochemical markers informing the diagnosis of sebaceous carcinoma and its distinction from its mimics: Adipophilin and Factor XIIIa to the rescue?

In this issue of the Journal of Cutaneous Pathology, Tjarks et al. present a study that advances our understanding of the diagnosis of sebaceous neoplasms (in particular, sebaceous carcinoma) and the lesions that mimic them (1).

Calciphylaxis with Pseudoxanthoma Elasticum-like Changes: A Case Series

BACKGROUND

Calciphylaxis and pseudoxanthoma elasticum (PXE) are rare, clinically distinct, disorders that share a common feature of cutaneous calcification that vary widely in their cutaneous presentation.

METHODS

We conducted a descriptive, retrospective review of biopsy specimens collected over a two-year period. Only specimens with a histologic and clinical diagnosis of calciphylaxis were included in the review. Specimens were then histologically examined for features of pseudoxanthoma elasticum in the dermis and/or subcutaneous fat, utilizing hematoxylin and eosin staining. Von Kossa and Verhoeff-Van Gieson special stains were also performed to examine calcification and elastic fibers, respectively.

RESULTS

We reviewed 13 biopsy specimens from 9 patients with known clinical and histologic evidence of calciphylaxis, both uremic and non-uremic types. Upon reexamination, we found that 46.2% (n=6/13) of the specimens demonstrated concomitant PXE-like changes uniquely localized to the subcutaneous fat.

CONCLUSION

The presence of PXE-like changes in the subcutis may heighten suspicion for a diagnosis of calciphylaxis in the appropriate clinical setting and be helpful when classic histologic features are subtle or absent.

Folliculotropic mycosis fungoides presenting with a solitary lesion: clinicopathological features and long-term follow-up data in a series of nine cases

Folliculotropic mycosis fungoides (FMF) is a rare but distinct variant of mycosis fungoides (MF), histologically characterized by the presence of folliculotropic infiltrates, often with sparing of the epidermis, and clinically by the preferential involvement of the head and neck region.¹

Me and I Are Not Friends, Just Aquaintances: on Thought Insertion and Self-Awareness

Abstract

A group of philosophers suggests that a sense of mineness intrinsically contained in the phenomenal structure of all conscious experiences is a necessary condition for a subject to become aware of himself as the subject of his experiences i.e. self-awareness. On this view, consciousness necessarily entails phenomenal self-awareness. This paper argues that cases of delusions of thought insertion undermine this claim and that such a phenomenal feature plays little role in accounting for the most minimal type of self-awareness entailed by phenomenal consciousness. First, I clarify the main view endorsing this claim i.e. the Self-Presentational View of Consciousness and formulate the challenge from thought insertion. After, I offer a systematic evaluation of all the strategies used by the advocates of this view to deal with this challenge. Finally, I conclude that most of these strategies are unsatisfactory for they rest in unwarranted premises, imprecisions about the agentive nature of cognitive experiences, and especially, lack of distinction between the different ways in which subjects can become aware of their own thoughts.

Acknowledgment of Reviewers

Testicular torsion and reperfusion: evidences for biochemical and molecular alterations

Abstract

This study was done in order to determine the molecular and biochemical alterations following testicular torsion (TT) and torsion-reperfusion (TR). For this purpose, 54 male Wistar rats were divided into five groups as control group (n = 6) and experimental group subjected to 1, 2, 4, and 8 h unilateral left torsion induction (n = 12 in each group). After induction of TT, testicular samples were collected from each group (n = 6), and the other six rats of each group underwent the same period of reperfusion after TT and then were sampled. Histological changes, the mRNA and protein expression of heat shock protein-70 (Hsp70), and caspase-3 were examined using reverse transcriptase-PCR (RT-PCR) and immunohistochemistry, respectively. Testicular total antioxidant capacity (TAC), glutathione peroxidase (GSH-px), and malondialdehyde (MDA) levels were evaluated. The mRNA damage and DNA fragmentation were assessed. The TT and TR significantly reduced differentiation and spermiogenesis indices (p < 0.05). The TT- and TR-induced groups exhibited a severe reduction in Hsp70 expression as well as remarkable enhancement in caspase-3 expression. The TAC and GSH-px levels were decreased and the MDA content was increased in TT- and TR-induced groups. Finally, the TT and TR enhanced mRNA damage and DNA fragmentation. The TT- and TR-induced damaging oxidative stress, diminished Hsp70 expression, and enhanced caspase-3 mRNA and protein levels result in apoptosis following 1, 2, and 4 h. Whereas, following 8 h, TT and TR initiate the necrosis by inducing energy depletion as well as severe mRNA damage.

Taking Multiple Exposure Into Account Can Improve Assessment of Chemical Risks

Abstract

During work, operators may be exposed to several chemicals simultaneously. Most exposure assessment approaches only determine exposure levels for each substance individually. However, such individual-substance approaches may not correctly estimate the toxicity of 'cocktails' of chemicals, as the toxicity of a cocktail may differ from the toxicity of substances on their own. This study presents an approach that can better take into account multiple exposure when assessing chemical risks. Almost 30000 work situations, monitored between 2005 and 2014 and recorded in two French databases, were analysed using MiXie software. The algorithms employed in MiXie can identify toxicological classes associated with several substances, based on the additivity of the selected effects of each substance. The results of our retrospective analysis show that MiXie was able to identify almost 20% more potentially hazardous situations than identified using a single-substance approach. It therefore appears essential to review the ways in which multiple exposure is taken into account during risk assessment.

Seven years of clinical experience with the Yeast Traffic Light PNA FISH: assay performance and possible implications on antifungal therapy

Abstract

We evaluated the performance of Yeast Traffic Light PNA FISH (YTL PNA FISH) in identification of Candida spp. from blood cultures. A total of 200 new episodes of candidemia were analysed prospectively. The YTL PNA FISH results were reported to the clinicians and data on antifungal therapy was documented. In total, there were 164/200 (82%) positive blood culture bottles with monomicrobial growth. Coverage of monomicrobial yeasts was 150/164 (91.5%). YTL PNA FISH could identify 23/24 (95.8%) Candida spp. in bottles with concomitant growth of bacteria and one yeast. Growth of two or more different yeasts was observed in 12/200 (6%) blood culture bottles and the method could identify all yeasts in 8/12 (66.7%). Data on antifungal treatment was available for 181/200 patients (90.5%). In 132/137 (96.4%) samples from patients without antifungal treatment, YTL PNA FISH could identify the Candida spp. or gave a negative result for yeasts not included in panel, and based on the result guide appropriate antifungal therapy the same day when the blood culture bottle signaled positive. The present study shows that YTL PNA FISH is a rapid, reliable diagnostic method which significantly reduces time delay for choice of appropriate antifungal therapy for critically ill patients.

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Undiagnosed Diabetes Mellitus in Community-Acquired Pneumonia: A Prospective Cohort Study

Abstract

Background

Diabetes mellitus is an important risk factor for community-acquired pneumonia, whereas the prevalence of undiagnosed diabetes mellitus and prediabetes in patients with community-acquired pneumonia is largely unknown. We aimed to determine the prevalence of prediabetes, undiagnosed diabetes mellitus, and risk factors associated with undiagnosed diabetes mellitus in a large European community-acquired pneumonia cohort.

Methods

This was a multicenter prospective cohort study of hospitals and private practices in Germany and Austria encompassing 1961 adults with community-acquired pneumonia included in the German Community-Acquired Pneumonia Competence Network (CAPNETZ) study between 2007 and 2014. The prevalence of undiagnosed diabetes mellitus and prediabetes was estimated based on hemoglobin A1c measurements. Logistic regression was used to assess risk factors for undiagnosed diabetes mellitus.

Results

Fifteen percent of patients had known diabetes mellitus. Among patients without known diabetes mellitus, 5.0% had undiagnosed diabetes mellitus and 37.5% had prediabetes. Male sex (odds ratio [OR], 2.45 [95% confidence interval {CI}, 1.35–4.45]), body mass index ≥25 kg/m² (OR, 2.64 [95% CI, 1.48–4.72]), and hyperglycemia at admission (6–11 mM: OR, 2.93 [95% CI, 1.54–5.60] and ≥11 mM: OR, 44.76 [95% CI, 17.58–113.98]) were associated with undiagnosed diabetes mellitus. Patients with undiagnosed diabetes mellitus had a higher 180-day mortality rate compared to patients without diabetes mellitus (12.1% vs 3.8%, respectively; P = .001).

Conclusions

Undiagnosed diabetes mellitus was prevalent among community-acquired pneumonia. Male sex, overweight, and hyperglycemia at admission were associated with undiagnosed diabetes mellitus. The long-term mortality among patients with undiagnosed diabetes mellitus was high compared to patients without diabetes mellitus.