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People with HIV (PWH) are living longer and healthier lives; thanks to combination antiretroviral therapy. As many PWH age, they find themselves providing care to family members and friends, just as their counterparts without HIV. The literature indicates that becoming a caregiver creates conditions that compromise one's cognitive function. Additionally, nearly 45% of all PWH experience HIV-associated neurocognitive disorder and are already vulnerable to cognitive impairment due to HIV, aging, and accompanying health conditions, and lifestyle factors. Given what is known, we assert that caregivers with HIV, especially as they age, are at additional risk for developing cognitive impairments. The purpose of this commentary was to briefly examine the juxtaposition between cognitive vulnerability of caregiving and the cognitive vulnerability of aging with HIV. Potential factors contributing to impaired cognition include stress, lack of social support, stigma, lifestyle, and comorbidities. Implications for clinical practice and research are provided.

Proteins have gained increasing success as therapeutic agents; however, challenges exist in effective and efficient delivery. In this work, we present a simple and versatile method for encapsulating proteins via complex coacervation with oppositely charged polypeptides, poly(l-lysine) (PLys) and poly(d/l-glutamic acid) (PGlu). A model protein system, bovine serum albumin (BSA), was incorporated efficiently into coacervate droplets via electrostatic interaction up to a maximum loading of one BSA per PLys/PGlu pair and could be released under conditions of decreasing pH. Additionally, encapsulation within complex coacervates did not alter the secondary structure of the protein. Lastly the complex coacervate system was shown to be biocompatible and interact well with cells in vitro. A simple, modular system for encapsulation such as the one presented here may be useful in a range of drug delivery applications.

Cognitive impairments have been endemic to the HIV epidemic since its beginning and persist to this day. These impairments are attributed to HIV-induced neuroinflammation, the long-term effects of combination antiretroviral therapy, lifestyle factors (e.g., sedentary behavior, substance use), neuro-comorbidities (e.g., depression), age-associated comorbidities (e.g., heart disease, hypertension), and others causes. Normal aging and lifestyle also contribute to the development of cognitive impairment. Regardless of the etiology, such cognitive impairments interfere with HIV care (e.g., medication adherence) and everyday functioning (e.g., driving safely, financial management). With more than half of people with HIV (PWH) 50 years and older, and ~45% of all PWH meeting the criteria for HIV-Associated Neurocognitive Disorder (HAND), those aging PWH are more vulnerable for developing cognitive impairment. This article provides an update to a social work model to identify and monitor PWH for cognitive impairment. Within this update, the state of the science on protecting brain health and cognitive reserve within the context of neuroHIV is also presented. From this, implications for practice and policy to promote successful cognitive functioning in older PWH are provided.

Oral carbohydrate consumption before surgery improves insulin sensitivity, cardiac output and well-being, and shortens hospital stays without adverse effects. No work has compared higher-dose carbohydrate beverages made for preoperative consumption to common, commercial oral rehydration solutions with lower carbohydrate concentrations. We recruited low-risk women undergoing scheduled cesarean deliveries with planned spinal anesthesia. Participants were randomized to one of three groups: those who consumed Clearfast® beverage, those who consumed Gatorade Thirst Quencher® beverage, or fasting control. Participants in the two beverage groups received 710 mL of the appropriate beverage the night before surgery and 355 mL 2 h before surgery. Participants in the control group fasted after midnight the night before surgery. Two hours before surgery, we recorded baseline patient well-being using visual analogue scales, followed by beverage consumption for subjects in the beverage groups. One hour later, we repeated the same assessment. Additional recorded measures included cord blood glucose level, intraoperative variables, breastfeeding success, and a quality of recovery assessment administered 1 day after surgery. Forty-seven patients were recruited: 15 received Clearfast®, 17 received Gatorade Thirst Quencher®, and 15 patients fasted after midnight. Group differences in change in patient well-being using visual analog scales were analyzed using linear regression. Both beverage-consuming groups showed significant improvements in patient well-being using visual analog scales while fasted patients showed no change. Either a common oral rehydration beverage or a higher-dose carbohydrate beverage consumed preoperatively resulted in superior well-being compared to fasting. No differences in other outcomes were noted. This study was registered on ClinicalTrials.gov with clinical trial registration number: NCT02684513.

Named after the two 1998 U.S. Supreme Court decisions that established it, the Ellerth/Faragher defense is an affirmative defense generally available to employers who would otherwise be held liable for Title VII claims of supervisor harassment. If the supervisor’s behavior does not involve an adverse employment action, the employer may avoid liability if it can demonstrate that: (1) the employer exercised reasonable care to prevent and promptly correct unlawful harassment in the workplace, and (2) the aggrieved employee unreasonably failed to take advantage of any preventative or corrective opportunities provided by the employer or to avoid harm otherwise. As employers sought to implement measures that demonstrated reasonable care, sexual harassment training and anonymous phone hotlines emerged as common strategies to assert this affirmative defense. In the contemporary workplace, where digital communication reigns and remote working becomes the new norm, such mechanisms are both archaic and ineffective in the prevention and correction of sexual harassment. This Comment critically analyzes the federal judiciary’s low threshold for “reasonableness” under the Ellerth/Faragher defense, considering specifically interdisciplinary understandings of the dynamics that motivate sexual harassment and rapid advances in technology. In addressing the law’s outdated understanding ofreasonableness, the Comment proposes the federal judiciary should (1) reexamine what qualifies as reasonable in the #MeToo era, and (2) strongly consider arguments in favor of “reasonable” including more stringent standards of care for employers reflecting technological advancements. So long as the Ellerth/Faragher defense remains the law, it is incumbent upon the federal judiciary to seriously consider evidence demonstrating what is reasonable in the modern workplace. The goal of this Comment is to suggest a comprehensive interdisciplinary approach with real-world impact—toprevent sexual harassment, rather than to correct—which carries the added benefit of mitigating employer liability.

Silicon nitrides, deposited by capacitively coupled plasma (CCP)-type plasma enhanced atomic layer deposition (PEALD), are generally applied to today’s nanoscale semiconductor devices, and are currently being investigated in terms of their potential applications in the context of flexible displays, etc. During the PEALD process, 13.56 MHz rf power is generally employed for the generation of reactive gas plasma. In this study, the effects of a higher plasma generation frequency of 162 MHz on both plasma and silicon nitride film characteristics are investigated for the purpose of silicon nitride PEALD, using bis(diethylamino)silane (BDEAS) as the silicon precursor, and N2 plasma as the reactant gas. The PEALD silicon nitride film deposited using the 162 MHz CCP exhibited improved film characteristics, such as reduced surface roughness, a lower carbon percentage, a higher N/Si ratio, a lower wet etch rate in a diluted HF solution, lower leakage current, and higher electric breakdown field, and more uniform step coverage of the silicon nitride film deposited in a high aspect ratio trench, as compared to silicon nitride PEALD using 13.56 MHz CCP. These improved PEALD silicon nitride film characteristics are believed to be related to the higher ion density, higher reactive gas dissociation, and lower ion bombardment energy to the substrate observed in N2 plasma with a 162 MHz CCP.

Oral carbohydrate consumption before surgery improves insulin sensitivity, cardiac output and well-being, and shortens hospital stays without adverse effects. No work has compared higher-dose carbohydrate beverages made for preoperative consumption to common, commercial oral rehydration solutions with lower carbohydrate concentrations.We recruited low-risk women undergoing scheduled cesarean deliveries with planned spinal anesthesia. Participants were randomized to one of three groups: those who consumed ClearfastForty-seven patients were recruited: 15 received ClearfastEither a common oral rehydration beverage or a higher-dose carbohydrate beverage consumed preoperatively resulted in superior well-being compared to fasting. No differences in other outcomes were noted.This study was registered on ClinicalTrials.gov with clinical trial registration number: NCT02684513.

Aim Fetal acetylcholine receptor inactivation syndrome (FARIS) occurs in offspring of mothers affected by myasthenia gravis (MG), from in-utero exposure to acetylcholine receptor (AChR)-antibodies targeting the fetal AChR γ-subunit. FARIS causes damage to the fetal neuromuscular junction which is crucial in muscle development, causing a persistent myopathy. FARIS may initially be mistaken for Transient Neonatal Myasthenia Gravis (TNMG), congenital neuromuscular disorders and one of the many causes of neonatal hypotonia. This study aimed to determine the clinical spectrum of FARIS and assess oral salbutamol as a novel pharmacological therapy. Methods Detailed review of antenatal and postnatal clinical features in novel FARIS cases seen in international neuromuscular centres. Antibody data analysis was performed at the Oxford neuroimmunology research laboratory. Oral salbutamol was trialled in five cases based on previously reported benefit in one of our patients. Results We identified 12 novel FARIS cases. At delivery resuscitation was required in all and intubation in nine, all had severe generalised hypotonia. Two infants with arthrogryphosis-multiplex-congenita phenotype died in the neonatal period. Among survivors, there was requirement for mechanical ventilation (n=9), NIPPV (n=2), oxygen (n=1), and supplemental NG/PEG feeding (n=12). The presence of severe generalised hypotonia with dysmorphic features prompted investigations for other neuromuscular, genetic and metabolic disorders which were negative. Common features included facial weakness (n=12) and limb contractures (n=9). Newly described disease features: diaphragmatic paresis (n=5), hearing impairment (n=3), CNS involvement (n=3), pyloric stenosis (n=2), extra-ocular eye restriction (n=2), non-progressive scoliosis (n=2), and jaw opening contracture(n=1). Motor development of patients improved with time. Respiratory complications (tracheostomy;n=2), feeding difficulties (PEG;n=2), facial weakness and speech impairment (from velopharyngeal incompetence) persisted in most. TNMG treatments(immunotherapy/pyridostigmine) were little or no benefit. Novel use of oral salbutamol improved fatiguability, ptosis, oromotor dysfunction, muscle tone, articulation and voice volume in all patients. In 8/12 pregnancies maternal myasthenia gravis hadn’t been established antenatally, and many mothers were pauci/asymptomatic. All had AChR-antibodies targeting the fetal γ-subunit confirming diagnosis. Where subsequent pregnancies were treated aggressively(immunotherapy), infants had improved outcomes. Conclusions This report demonstrates and expands the phenotypic spectrum of FARIS, and emphasises oral salbutamol therapy as a potentially beneficial treatment. FARIS should be considered (mothers or infants tested for fetal specific AChR-Abs) in infants presenting with neonatal hypotonia, myopathic features and/or a suggestive antenatal history, even in the absence of a maternal MG diagnosis. Aggressive treatment with immunotherapy in pregnancy may improve outcomes.

Introduction Pancreatic resection is technically difficult and has higher postoperative mortality and morbidity rates than those of other abdominal operations. As the incidence of postoperative morbidity and mortality has gradually decreased, some centers have reported remarkable achievements by attempting minimally invasive surgery. This study was performed to investigate the chronological trends of pancreatectomies by analyzing a large-scale database. Methods The medical records of 5,175 patients who underwent pancreatic resection between 1961 and 2019 at a single institution were collected and reviewed. The chronological trend of surgical outcome was investigated by dividing the period into 5-year intervals. To investigate the chronological change in survival outcomes of periampullary cancer, the survival data of 3,108 patients were analyzed. Results Patient age and the proportion of pancreatic cancer have increased over time. Pancreatic cancer was most common (35.9%) in 2015-2019, followed by pancreatic cyst (24.8%), common bile duct cancer (13.4%), and ampulla of Vater cancer (10.1%). The incidence of postoperative complications tended to decrease over time (26.0% in 2000-2004 and 20.8% in 2015-2019). A comparison of survival outcomes of periampullary malignancies by period revealed that pancreatic cancer significantly improved (5-year survival rate: 14.4% before 2000 vs. 15.2% in 2000-2009 vs. 29.0% after 2009, p < 0.001). Conclusions Postoperative complication rate and duration of recovery have improved in pancreatic resection over time. The proportion of minimally invasive pancreatectomies is gradually increasing. To improve outcomes in the future, active multidisciplinary approach and postoperative management are needed.

The purpose of this article is to review the available data regarding the application and therapeutic outcomes of laser therapy for the treatment of genitourinary syndrome of menopause (GSM). There have been several studies regarding the use of laser therapy for the treatment of GSM. Most of these studies show a trend toward safe and effective treatment in the short term (less than or equal to 12 weeks). However, these studies are lacking in randomization, blinding, placebo, and comparison groups. Although laser therapy for the treatment of the symptoms of GSM appears promising, there is currently a lack of high-level and long-term evidence regarding its safety and efficacy. There is also a lack of professional guidelines in the USA regarding this modality of treatment, specifically for GSM. Opportunities exist for future research in this area, specifically to determine safety and long-term outcomes of therapy.

Here we present a miniaturized analog of a blinking human eye to reverse engineer the complexity of the interface between the ocular system and the external environment. Our model comprises human cells and provides unique capabilities to replicate multiscale structural organization, biological phenotypes and dynamically regulated environmental homeostasis of the human ocular surface. Using this biomimetic system, we discovered new biological effects of blink-induced mechanical forces. Furthermore, we developed a specialized in vitro model of evaporative dry-eye disease for high-content drug screening. This work advances our ability to emulate how human physiological systems interface with the external world, and may contribute to the future development of novel screening platforms for biopharmaceutical and environmental applications.

Summary Background Maintenance of water balance in the stratum corneum (SC) is determined by the content of intercellular lipids and natural moisturizing factors (NMFs) in corneocytes. Aim To investigate the association between the NMFs and (pro)filaggrin and the proteases responsible for the processing of (pro)filaggrin to NMFs in the SC of hydrated and dry skin areas of healthy human subjects. Methods The SC hydration state and the transepidermal water loss (TEWL) were measured using a Corneometer and a Tewameter, respectively. Proteases, (pro)filaggrin and NMFs were extracted from SC samples obtained by tape-stripping of the tested skin. Expression levels of (pro)filaggrin were determined by dot blotting and western blotting, and total NMFs by ultra-high performance liquid chromatography. Expression of the proteases caspase-14, calpain-1 and bleomycin hydrolase was measured by western blotting. Results The levels of (pro)filaggrin were not significantly different between hydrated and dry skin, whereas the level of total NMFs was significantly reduced in dry skin. A negative correlation between (pro)filaggrin and NMFs was found in dry skin (Pearson correlation coefficient r = − 0.57, *P

Objectives/Hypothesis The clinical features and treatment outcomes of benign paroxysmal positional vertigo (BPPV) are known to be different depending on the type of and involved canal. This difference could be due to differences in the functional change of the otolith organ. Study Design Case series. Methods Forty-nine patients were diagnosed to primary BPPV; 18 were categorized as posterior canal canalolithiasis (PC canalolithiasis), and 31 were categorized as horizontal canal (HC) BPPV with canalolithiasis or cupulolithiasis (HC canalolithiasis or HC cupulolithiasis). Diagnostic interventions to measure vestibular functions were performed such as electronystagmography (ENG), videonystagmography (VNG), and static and dynamic subjective visual vertical (SVV). BPPV was confirmed with nystagmus during positioning/positional test under ENG and VNG. Static SVV was recorded with a light-emitting diode (LED) bar located in front of the patients before eccentric rotation and dynamic SVV was recorded during eccentric rotation with the LED bar. SVV angles were read by the examiner and analyzed. The measured values were compared to those of normal controls and each other. Results Dynamic SVV toward the lesion side in all subtypes of BPPV were significantly different from those of the controls; HC cupulolithiasis showed significantly lower values than those of PC canalolithiasis and HC canalolithiasis. Conclusions HC cupulolithiasis shows a lesser degree of utricular dysfunction compared with other subtypes. It could postulate the difference of pathophysiology between canalolithiasis and cupulolithiasis. Level of Evidence 4. Laryngoscope, 124:984–988, 2014

Background Polymeric modification of islet surface is highly effective in preventing transplanted islets against host immune reactions. However, grafted islets are eventually rejected by the host immune reaction. Thus, repetitive islet transplantation is needed to treat type 1 diabetic patients experiencing graft rejection. We explored whether using poly(ethylene glycol) (PEG) as surface camouflage of islets (PEGylation) can be an affordable immunoprotective remedy for repeated islet transplantation. Methods The surface coverage of PEG was evaluated in vitro. The viability of PEGylated islets cocultured with sensitized or nonsensitized splenocytes was evaluated using lactate dehydrogenase assay. In addition, the effect of surface modification on immunoprotection for repetitively transplanted islets was evaluated in a sensitized rat model. Results Unmodified islets transplanted in combination with Cyclosporine (CsA) and anti-CD4 monoclonal antibody (OX-38) into the sensitized recipients did not maintain a normal level of blood glucose over 20 days. Interestingly, however, three of the five recipients became normoglycemic up to 30 days when PEGylated islets were transplanted in combination with CsA and OX-38. Conclusion These results demonstrated that PEGylation alone was not an affordable immunoprotective method, but the combination of CsA and OX-38 along with PEGylation showed a highly improved a synergic effects on the inhibition of sensitized host immune reactions.

Background Rejection and hypoxia are important factors causing islet loss at an early stage after pancreatic islet transplantation. Recently, islets have been dissociated into single cells for reaggregation into so-called islet spheroids. Herein, we used a hanging-drop strategy to form islet spheroids to achieve functional equivalence to intact islets. Methods To obtain single islet cells, we dissociated islets with trypsin-EDTA digestion for 10 minutes. To obtain spheroids, we dropped various numbers of single cells (125, 250, or 500 cells/30 μL drop) onto a Petri dish, that was inverted for incubation in humidified air containing 5% CO2 at 37°C for 7 days. The aggregated spheroids in the droplets were harvested for further culture. Results The size of the aggregated islet spheroids depended on the number of single cells (125–500 cells/30 μL droplet). Their morphology was similar to that of intact islets without any cellular damage. When treated with various concentrations of glucose to evaluate responsiveness, their glucose-mediated stimulation index value was similar to that of intact islets, an observation that was attributed to strong cell-to-cell interactions in islet spheroids. However, islet spheroids aggregated in general culture dishes showed abnormal glucose responsiveness owing to weak cell-to-cell interactions. Cell-to-cell interactions in islet spheroids were confirmed with an anti–connexin-36 monoclonal antibody. Finally, nonviral poly(ethylene imine)–mediated interleukin-10 cytokine gene delivered beforehand into dissociated single cells before formation of islet spheroids increased the gene transfection efficacy and interleukin-10 secretion from islet spheroids >4-fold compared with intact islets. Conclusion These results demonstrated the potential application of genetically modified, functional islet spheroids with of controlled size and morphology using an hanging-drop technique.

The nuclear level density and the γ -ray strength function have been extracted for 89 Y by using the Oslo method on 89Y(p,p′γ)89Y coincidence data. The γ-ray strength function displays a low-energy enhancement consistent with previous observations in this mass region (93–98Mo). Shell-model calculations support the conclusion that the observed enhancement is due to strong, low-energy M1 transitions at high excitation energies. The data were further used as input for calculations of the 88 Sr(p,γ )89 Y and 88 Y(n,γ )89 Y cross sections with the TALYS reaction code. Comparison with cross-section data, where available, as well as with values from the BRUSLIB library, shows a satisfying agreement.

Summary What is known and Objective: Acarbose, an α-glycosidase inhibitor, is used to treat diabetic patients. Pharmacokinetic evaluation of acarbose is difficult because

Background: Cathepsin G, a serine protease that is activated by ultraviolet (UV) radiation, increases matrix metalloproteinase-1 (MMP-1) expression in fibroblasts through fibronectin (Fn) fragmentation and promotes the conversion of proMMP-1 to active MMP-1. Objectives: This study investigated whether [2-[3-[[(1-benzoyl-4-piperidinyl)methylamino]carbonyl]-2-naphthalenyl]-1-(1-naphthalenyl)-2-oxoethyl]-phosphonic acid (KPA), a cathepsin G inhibitor, plays any role in extracellular matrix (ECM) damage in an in vitro 3D dermal equivalent (DE) and an in vivo ultraviolet B (UVB)-irradiated hairless mice. Methods: We examined the potential ECM-protective effects of a cathepsin G inhibitor in an in vitro 3D DE model and an in vivo UVB-irradiated hairless mouse skin model. Results: Among five known serine protease inhibitors, KPA showed the strongest potency and selectivity against cathepsin G. KPA inhibited the cathepsin G-mediated MMP-1 increase and alleviated the downregulation of mRNAs encoding collagen and tissue inhibitor of matrix metalloproteinase-1 in an in vitro 3D DE model. Most importantly, topical application of KPA (0.025%) to the dorsal skin of hairless mice enhanced collagen expression and attenuated UVB-induced Fn fragmentation and upregulation of MMP-2 and MMP-9 activities. Conclusions: Cathepsin G inhibitors may be useful for the prevention of UVB-induced photoaging through amelioration of ECM damage and MMP upregulation.

To cite this article: Cheong HS, Park S-M, Kim M-O, Park J-S, Lee JY, Byun JY, Park BL, Shin HD, Park C-S. Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics. Allergy 2011; 66: 637–644. Abstract Background: In addition to the dysregulation of arachidonic acid metabolism in aspirin-intolerant asthma (AIA), aspirin acetylsalicylic acid (ASA) exerts effects on inflammation and immunity; however, many of these effects are unknown. Objective: The aim of the study was to evaluate the methylation status of whole genome in blood and polyp tissues with and without aspirin hypersensitivity. Methods: Genome-wide DNA methylation levels in nasal polyps and peripheral blood cells were examined by microarray analysis using five subjects with AIA and four subjects with aspirin-tolerant asthma (ATA). Results: In the nasal polyps of the patients with AIA, hypermethylation was detected at 332 loci in 296 genes, while hypomethylation was detected at 158 loci in 141 genes. Gene ontologic and pathway enrichment analyses revealed that genes involved in lymphocyte proliferation, cell proliferation, leukocyte activation, cytokine biosynthesis, cytokine secretion, immune responses, inflammation, and immunoglobulin binding were hypomethylated, while genes involved in ectoderm development, hemostasis, wound healing, calcium ion binding, and oxidoreductase activity were hypermethylated. In the arachidonate pathway, PGDS, ALOX5AP, and LTB4R were hypomethylated, whereas PTGES was hypermethylated. Conclusion: The nasal polyps of patients with AIA have characteristic methylation patterns affecting 337 genes. The genes and pathways identified in this study may be associated with the presence of aspirin hypersensitivity in asthmatics and are therefore attractive targets for future research.

Lipomatous haemangiopericytoma (a fat-forming solitary fibrous tumour) is a rare soft-tissue tumour histologically characterized by haemangiopericytomatous vasculature and the presence of mature adipocytes. We report the CT and MRI findings of a case of lipomatous haemangiopericytoma involving the perineum. CT showed a well-circumscribed soft-tissue density mass containing a small area of fat density and a punctuate calcification. On MR images, the mass was mostly isointense to the muscle on T(1) weighted images, with heterogeneous signal intensity on T(2) weighted images, and showed strong contrast enhancement except for the fatty and dense collagenous components. This is the first case report of imaging findings of a lipomatous haemangiopericytoma in the radiological literature. Although rare, lipomatous haemangiopericytoma should be considered as a differential diagnosis of fat-containing, hypervascular soft-tissue tumours with variable signal intensity on T(2) weighted images.