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Abstract Introduction The impacts of prurigo nodularis (PN) on healthcare resource utilization (HCRU) and associated costs are unclear. Methods This retrospective, cross-sectional claims analysis (IQVIA PharMetrics® Plus) compared HCRU and costs over 1 year in adults with PN versus matched controls (region, payer type, age, sex, year) from 2016 to 2019, and also in patients with PN receiving advanced versus localized/no therapy. For patients with data in multiple calendar years, 1 year was randomly selected. Outcomes were compared by chi-square tests, t tests, or negative binomial tests. Results We matched 16,888 patients with PN with 16,888 controls. Most comorbidities (mental health, metabolic conditions, type 2 inflammatory diseases) appeared more frequently in patients with PN versus controls. HCRU was significantly (P

Abstract The voltage-gated calcium channel (VGCC) subunit complex is comprised of the α1 subunit, the ion-permeable channel, and three auxiliary subunits: β, α2δ, and γ. β is the most extensively studied auxiliary subunit and is necessary for forward trafficking of the α1 subunit to the plasma membrane. VGCCs mediate voltage-dependent movement of calcium ions into neuronal cytoplasm, including at dendrites, where intracellular calcium spikes initiate signaling cascades that shape the structural plasticity of dendritic spines. Genetic studies strongly implicate calcium signaling dysfunction in the etiology of neurodevelopmental disorders including schizophrenia. Dendritic spine density is significantly decreased in schizophrenia in the primary auditory cortex where it is driven by the loss of small spines, and small spine loss associated with increased peptide levels of ALFDFLK found in the VGCC β subunit β4. Overexpressing the gene that encodes the voltage-gated calcium channel subunit β4, CACNB4, selectively reduced small spine density in vitro. In the current study we extended this observation in an intact mammalian system within a relevant neurodevelopmental context. We overexpressed CACNB4 in early development, assessed spine density and morphology in adult male and female mouse cortex, and characterized β1-4 protein levels and β4 protein-protein interactions. Overexpression reduced small spine density in females. This effect was not dependent on the estrous stage. Instead, it corresponded to sex differences in the murine β4 interactome. The VGCC subunit β1b was significantly enriched in the β4 interactome of male relative to female mice, and thus may have served to mitigate VGCC overexpression-mediated spine loss in male mice.

Abstract Disease freedom surveillance is challenging in settings where environmental conditions and population health can change abruptly. We propose a novel approach to freedom evaluation that is specifically suited to open environments. The approach merges information about pathogen introduction risk with information from pathogen surveillance to estimate assurance of freedom. While the logic is not new, the approach uses a generalizable model designed by an expert panel to estimate introduction probability, easing the need for costly, site‐specific risk assessment. This introduction probability is then used to inform the time‐adjusted value of historical surveillance data and adapt the consequent requirements (sampling volume and frequency) of future surveys. We apply the approach to an open water region on the Pacific Coast of the United States known for its mollusk production. Results support absence of the target pathogens—Marteilia refringens, Marteilioides chungmuensis, Ostreid herpesvirus 1, Perkinsus marinus, and Perkinsus olseni—for the host species, region, and time‐period under investigation. Findings demonstrate (1) the ability to retain assurance in pathogen freedom through time in open systems, (2) the limitations of sample volume, and importance of sampling frequency, for pathogens with higher introduction risk, and (3) expert elicitation as a generalizable alternative to formal risk assessment.

Abstract The explosion of artificial intelligence, the possible end of Moore's law, dawn of quantum computing, and the continued exponential growth of data communications traffic have brought new urgency to the need for laser integration on the diversified Si platform. While diode lasers on group III‐V platforms have long‐powered internet data communications and other optoelectronic technologies, direct integration with Si remains problematic. A paradigm‐shifting solution requires exploring new and unconventional materials and integration approaches. In this work, it is shown that a sub‐10‐nm ultra‐thin Si1−xGex buffer layer fabricated by an oxidative solid‐phase epitaxy process can facilitate extraordinarily efficient strain relaxation. The Si1−xGex layer is formed by ion implanting Ge into Si(111) and selectively oxidizing Si atoms in the resulting ion‐damaged layer, precipitating a fully strain‐relaxed Ge‐rich layer between the Si substrate and surface oxide. The efficient strain relaxation results from the high oxidation temperature, producing a periodic network of dislocations at the substrate interface, coinciding with modulations of the Ge content in the Si1−xGex layer and indicating the presence of defect‐mediated diffusion of Si through the layer. The epitaxial growth of high‐quality GaAs is demonstrated on this ultra‐thin Si1−xGex layer, demonstrating a promising new pathway for integrating III‐V lasers directly on the Si platform.

Abstract Atherosclerosis is an inflammatory disorder responsible for cardiovascular disease. Reactivation of efferocytosis, the phagocytic removal of cells by macrophages, has emerged as a translational target for atherosclerosis. Systemic blockade of the key ‘don’t-eat-me’ molecule, CD47, triggers the engulfment of apoptotic vascular tissue and potently reduces plaque burden. However, it also induces red blood cell clearance, leading to anemia. To overcome this, we previously developed a macrophage-specific nanotherapy loaded with a chemical inhibitor that promotes efferocytosis. Because it was found to be safe and effective in murine studies, we aimed to advance our nanoparticle into a porcine model of atherosclerosis. Here, we demonstrate that production can be scaled without impairing nanoparticle function. At an early stage of disease, we find our nanotherapy reduces apoptotic cell accumulation and inflammation in the atherosclerotic lesion. Notably, this therapy does not induce anemia, highlighting the translational potential of targeted macrophage checkpoint inhibitors.

Abstract Background The literature shows conflicting results regarding inter- and intra-rater reliability, even for the same movement screen. The purpose of this study was to assess inter- and intra-rater reliability of movement scores within and between sessions of expert assessors and the effects of body-shape on reliability during a movement screen using a custom online visualisation software. Methods Kinematic data from 542 athletes performing seven movement tasks were used to create animations (i.e., avatar representations) using motion and shape capture from sparse markers (MoSh). For each task, assessors viewed a total of 90 animations. Using a custom developed visualisation tool, expert assessors completed two identical sessions where they rated each animation on a scale of 1–10. The arithmetic mean of weighted Cohen’s kappa for each task and day were calculated to test reliability. Results Across tasks, inter-rater reliability ranged from slight to fair agreement and intra-rater reliability had slightly better reliability with slight to moderate agreement. When looking at the average kappa values, intra-rater reliability within session with and without body manipulation and between sessions were 0.45, 0.37, and 0.35, respectively. Conclusions Based on these results, supplementary or alternative methods should be explored and are likely required to increase scoring objectivity and reliability even within expert assessors. To help future research and practitioners, the custom visualisation software has been made available to the public.

Background A multitude of factors are considered in an infectious disease (ID) training program’s meticulous selection process of ID fellows but their correlation to pre and in-fellowship academic success as well as post-fellowship academic success and short-term outcomes is poorly understood. Our goal was to investigate factors associated with subsequent academic success in fellowship as well as post-fellowship short-term outcomes.Methods In 2022, we retrospectively analyzed deidentified academic records from 39 graduates of the Mayo Clinic Rochester ID Fellowship Program (1 July 2013- 30 June 2022). Data abstracted included demographics, degrees, honor society membership, visa/citizenship status, medical school, residency training program, United States Medical Licensure Exam (USMLE) scores, letters of recommendation, in-training examination (ITE) scores, fellowship track, academic rank, career choice, number of honors, awards, and abstracts/publications prior to fellowship, during training, and within 2 years of graduation.Results Younger fellows had higher USMLE step 1 scores, pre and in-fellowship scholarly productivity, and higher ITE performance. Female fellows had significantly higher USMLE step 3 scores. Prior research experience translated to greater in-fellowship scholarly productivity. Higher USMLE scores were associated with higher ID ITE performance during multiple years of fellowship, but USMLE step 2 clinical knowledge and 3 scores were associated with higher pre and in-fellowship scholarly productivity and receiving an award during fellowship. The USMLE step 1 score did not correlate with fellowship performance beyond year 1 and 2 ITE scores.Conclusions Multiple aspects of a prospective fellow’s application must be considered as part of a holistic review process for fellowship selection. USMLE step 2 CK and 3 scores may predict fellowship performance across multiple domains.

Targeting antigens with antibodies exhibiting pH/Ca2+-dependent binding against an antigen is an attractive strategy to mitigate target-mediated disposition and antigen buffering. Studies have reported improved serum exposure of antibodies exhibiting pH/Ca2+-binding against membrane-bound receptors. Asialoglycoprotein receptor 1 (ASGR1) is a membrane-bound receptor primarily localized in hepatocytes. With a high expression level of approximately one million receptors per cell, high turnover, and rapid recycling, targeting this receptor with a conventional antibody is a challenge. In this study, we identified an antibody exhibiting pH/Ca2+-dependent binding to ASGR1 and generated antibody variants with increased binding to neonatal crystallizable fragment receptor (FcRn). Serum exposures of the generated anti-ASGR1 antibodies were analyzed in transgenic mice expressing human FcRn. Contrary to published reports of increased serum exposure of pH/Ca2+-dependent antibodies, the pH/Ca2+-dependent anti-ASGR1 antibody had rapid serum clearance in comparison to a conventional anti-ASGR1 antibody. We conducted sub-cellular trafficking studies of the anti-ASGR1 antibodies along with receptor quantification analysis for mechanistic understanding of the rapid serum clearance of pH/Ca2+-dependent anti-ASGR1 antibody. The findings from our study provide valuable insights in identifying the antigens, especially membrane bound, that may benefit from targeting with pH/Ca2+-dependent antibodies to obtain increased serum exposure.

Abstract BRCA2 is a tumor suppressor protein responsible for safeguarding the cellular genome from replication stress and genotoxicity, but the specific mechanism(s) by which this is achieved to prevent early oncogenesis remains unclear. Here, we provide evidence that BRCA2 acts as a critical suppressor of head-on transcription-replication conflicts (HO-TRCs). Using Okazaki-fragment sequencing (Ok-seq) and computational analysis, we identified origins (dormant origins) that are activated near the transcription termination sites (TTS) of highly expressed, long genes in response to replication stress. Dormant origins are a source for HO-TRCs, and drug treatments that inhibit dormant origin firing led to a reduction in HO-TRCs, R-loop formation, and DNA damage. Using super-resolution microscopy, we showed that HO-TRC events track with elongating RNA polymerase II, but not with transcription initiation. Importantly, RNase H2 is recruited to sites of HO-TRCs in a BRCA2-dependent manner to help alleviate toxic R-loops associated with HO-TRCs. Collectively, our results provide a mechanistic basis for how BRCA2 shields against genomic instability by preventing HO-TRCs through both direct and indirect means occurring at predetermined genomic sites based on the pre-cancer transcriptome.

Avian schistosomes are snail-borne trematode parasites (Trichobilharzia spp.) that can cause a nasty skin rash in humans when their cercariae mistake us for their normal bird hosts. We sought to investigate drivers of the spatial distribution of Trichobilharzia cercaria abundance throughout Northern Michigan lakes. For 38 sites on 16 lakes, we assessed several dozen potential environmental predictors that we hypothesized might have direct or indirect effects on overall cercaria abundance, based on known relationships between abiotic and biotic factors in wetland ecosystems. We included variables quantifying local densities of intermediate hosts, temperature, periphyton growth rates, human land use and hydrology. We also measured daily abundance of schistosome cercariae in the water over a 5-week period, supported by community scientists who collected and preserved filtered water samples for qPCR. The strongest predictor of cercaria abundance was Lymnaea host snail density. Lymnaea density was higher in deeper lakes and at sites with more deciduous tree cover, consistent with their association with cool temperature habitats. Contrary to past studies of human schistosomes, we also found a significant negative relationship between cercaria abundance and submerged aquatic vegetation, possibly due to vegetation blocking cercaria movement from offshore snail beds. If future work shows that these effects are indeed causal, then these results suggest possible new approaches to managing swimmer's itch risk in northern MI lakes, such as modifying tree cover and shallow-water vegetation at local sites.

Background: How frequently out-of-hospital cardiac arrest (OHCA) occurs within a reasonable walking distance to the nearest public automated external defibrillator (AED) has not been well studied. Methods: As Kansas City, Missouri has a comprehensive city-wide public AED registry, we identified adults with an OHCA in Kansas City during 2019–2022 in the Cardiac Arrest Registry to Enhance Survival. Using AED location data from the registry, we computed walking times between OHCAs and the nearest registered AED using the Haversine formula, a mapping algorithm to calculate walking distance in miles from one location to another. Results were stratified by OHCA location (home vs. public) and by whether the patient received bystander cardiopulmonary resuscitation (CPR). Results: Of 1,522 OHCAs, 1,291 (84.8%) occurred at home and 231 (15.2%) in public. Among at-home OHCAs, 634 (49.1%) received bystander CPR and no patients had an AED applied even as 297 (23.0%) were within a 4-minute walk to the closest public AED. Among OHCAs in public, 108 (46.8%) were within a 4-minute walk to the closest public AED. For public OHCAs within a 4-minute walk, bystanders applied an AED in 13 (12.0%) of these cases and in 24.5% (13/53) of those who received bystander CPR. Conclusion: In one U.S. city with a publicly available AED registry, there were no instances in which a bystander accessed a public AED for an OHCA at home. For OHCAs in public, nearly half occurred within a 4-minute walk to the closest AED but bystander use of an AED was low.

الملخص: أهدف البحث: تعكس عدد حالات كورونا في إندونيسيا خطورة الأمراض وانتشارها بسرعة. تم إجراء الرصد الجينومي لفيروس كورونا المستجد والتحقيق في المجتمعات البكتيرية للجهاز التنفسي العلوي في غرب جاوة كرد فعل للتهديد المتزايد حيث يمكن أن يؤثر تفاوت التوازن في الميكروبات في الجهاز التنفسي العلوي بشكل سلبي على حالة المرضى. طرق البحث: استخدمنا منصة تسلسل النانوبور لتحليل 43 عينة من التغيرات الجينية لفيروس كورونا المستجد و11 عينة مختارة لتسلسل الجينات عبر الريبوزوم 16، تم جمعهم في الفترة من مايو إلى أغسطس 2021. النتائج: خمسة أنواع فيروسية في السكان (أ.ي.23؛ أ.ي.24؛ أ.ي.26؛ أ.ي.42؛ ب.1.1.7) كانت تهيمن على وجود النوع أ.ي.23 (82%) predominated among five virus lineages in the populations (AY.23, AY.24, AY.26, AY.42, B.1.1.7). The region in the SARS-CoV-2 genome found to have the highest number of mutations was the spike (S) protein (>20%). There was no association between SARS-CoV-2 lineages, mutation frequency, patient profile, and COVID-19 rapid spread-categorized cases. There was no association of bacterial relative abundance, alpha-beta diversity, and linear discriminant analysis effect size analysis with patient profile and rapid spread cases. MetagenomeSeq analysis showed eight differential abundance species in individual patient profiles, including Pseudomonas aeruginosa and Haemophilus parainfluenzae. Conclusions: The data demonstrated relevant AY.23 dominance (the Delta variant) in West Java during that period supporting the importance of surveillance program in monitoring disease progression. The inconsistent results of the bacterial communities suggest that a complex multifactor process may contribute to the progression of bacterial-induced disease in each patient.

Background and Aims: Management of Crohn’s disease (CD) requires frequent monitoring for disease activity and response to therapy. In this study, we examined the clinical utility of a novel stool-derived eukaryotic RNA (seRNA)-based diagnostic in patients with CD. Methods: Stool samples were collected from 68 individuals for up to 3 time points prior to, and after initiation of an advanced therapy. Stool samples underwent RNA extraction and sequencing using a custom capture panel (n = 1507 transcripts). seRNA signatures were compared to Crohn's Disease Activity Index scores and endoscopies, when available. Random forest models classified disease severity when compared to Crohn's Disease Activity Index scores. seRNA signatures were also used to assess expression of the therapy target and cell type abundance at various time points. Results: Across all 102 samples collected from 68 individuals, the classifier successfully parsed individuals with active disease (n = 37) relative to those in remission (n = 65) with 87% sensitivity and 77% specificity, respectively. A second classifier, which was employed on subjects with active disease (n = 37), successfully parsed individuals with mild disease (n = 15) from those with moderate disease (n = 22) with 93% and 86% sensitivity, respectively. For the 16 subjects with longitudinal data, seRNA expression of the therapeutic target (eg, ITGA4/ITGB7 for vedolizumab or IL12/IL23 for ustekinumab) as well as lymphocyte burden was correlated with response. Conclusion: A novel seRNA and informatic-based method reliably discriminates active disease from remission and stratifies mild from moderate CD activity. This demonstrates preliminary feasibility to predict therapeutic response and assess disease activity for patients with CD.

Inconel 718 is a widely popular aerospace superalloy known for its high-temperature performance and resistance to oxidation, creep, and corrosion. Traditional manufacturing methods, like casting and powder metallurgy, face challenges with intricate shapes that can result in porosity and uniformity issues. On the other hand, Additive Manufacturing (AM) techniques such as Powder Bed Fusion (PBF) and Direct Energy Deposition (DED) can allow the creation of intricate single-part components to reduce weight and maintain structural integrity. However, AM parts often exhibit directional solidification, leading to anisotropic properties and potential crack propagation sites. To address this, post-processing treatments like HIP and heat treatment are necessary. This study explores the effects of the raster and stochastic spot melt scanning strategies on the microstructural and mechanical properties of IN718 parts fabricated using Electron Beam Powder Bed Fusion (EB-PBF). This research demonstrates that raster scanning produces columnar grains with higher mean aspect ratios. Stochastic spot melt scanning facilitates the formation of equiaxed grains, which enhances microstructural refinement and lowers anisotropy. The highest microstructural values were recorded in the raster-produced columnar grain structure. Conversely, the stochastic melt-produced transition from columnar to equiaxed grain structure demonstrated increased hardness with decreasing grain size; however, the hardness of the smallest equiaxed grain structure was slightly less than that of the columnar grain structure. These findings underscore the vital importance of scanning strategies in optimizing the EB-PBF process to enhance material properties.

Background: Majocchi's granuloma (MG) is an uncommon deep fungal folliculitis predominantly caused by dermatophytes. Given the rarity of this condition, available data regarding predisposing comorbidities/risk factors, clinical characteristics, offending microbiologic pathogens, diagnostics, pathologic findings, and treatment approaches has been inferred from historical cases. Objectives: To review our institutional experience with MG. Methods: We retrospectively analyzed a multicenter cohort of adult patients diagnosed with MG between 1992 and 2022. Results: We analyzed 147 patients with MG, 105 of which were male with a median age of 55.6 years. Immunosuppressant and topical corticosteroid use were common prior to development of MG. Dermatologic lesions and their sites of involvement did not differ based on the immune status of patients. Trichophyton rubrum was the most common causative pathogen of MG, in addition to other dermatophytes. Treatment duration for all prescribed agents was median 31.5 days with oral terbinafine being the most frequently utilized agent. Clinical resolution was achieved in 96.6% of cases. Limitations: Retrospective, nonrandomized study. Conclusions: Although rare and clinically variable in presentation, diagnosis of MG often requires histopathologic confirmation to subsequently direct prolonged treatment with systemic antifungal therapy for mycological cure.

Coarse-grained models describe the macroscopic mean response of a process at large scales, which derives from stochastic processes at small scales. Common examples include accounting for velocity fluctuations in a turbulent fluid flow model and cloud evolution in climate models. Most existing techniques for constructing coarse-grained models feature ill-defined parameters whose values are arbitrarily chosen (e.g., a window size), are narrow in their applicability (e.g., only applicable to time series or spatial data), or cannot readily incorporate physics information. Here, we introduce the concept of physics-guided Gaussian process regression as a machine-learning-based coarse-graining technique that is broadly applicable and amenable to input from known physics-based relationships. Using a pair of case studies derived from molecular dynamics simulations, we demonstrate the attractive properties and superior performance of physics-guided Gaussian processes for coarse-graining relative to prevalent benchmarks. The key advantage of Gaussian-process-based coarse-graining is its ability to seamlessly integrate data-driven and physics-based information.

Abstract Background For children aged 6–11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management. Objectives This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914). Methods Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight

Abstract Mammalian retinal metabolism favors aerobic glycolysis. However, the role of glycolytic metabolism in retinal morphogenesis remains unknown. We report that aerobic glycolysis is necessary for the early stages of retinal development. Taking advantage of an unbiased approach that combines the use of eye organoids and single-cell RNA sequencing, we identify specific glucose transporters and glycolytic genes in retinal progenitors. Next, we determine that the optic vesicle territory of mouse embryos displays elevated levels of glycolytic activity. At the functional level, we show that removal of Glucose transporter 1 and Lactate dehydrogenase A gene activity from developing retinal progenitors arrests eye morphogenesis. Surprisingly, we uncover that lactate-mediated upregulation of key eye-field transcription factors is controlled by the epigenetic modification of histone H3 acetylation through histone deacetylase activity. Our results identify an unexpected bioenergetic independent role of lactate as a signaling molecule necessary for mammalian eye morphogenesis.

Ankle fractures with associated dislocation of the ankle joint are a common injury presenting to emergency rooms. The first step in successful management of these injuries is with closed reduction of the dislocation and splinting in as close to anatomic alignment as possible. Infrequently, closed reduction cannot be obtained due to interposed soft tissues. In the case of ankle dislocations, subluxation of the posterior tibial tendon into the tibiofibular syndesmosis is a rare associated injury that may prevent proper reduction of the ankle mortise and, if not identified and corrected, results in a poor long-term outcome. We present a rare case of a young, healthy male college athlete who sustained a closed ankle dislocation injury with subluxation of the posterior tibial (PT) tendon through the ankle joint and into the tibiofibular syndesmosis. Additionally, we present a brief literature review and technique guide on the reduction and relocation of the posterior tibial tendon to hopefully serve as a reference for management of this rare injury type.

ABSTRACTDislocations form patterns that strongly influence mechanical properties. Prevailing theories are dichotomous: patterns either form by energy minimization or stochasticity during plastic flow. Using discrete dislocation dynamics simulations, it is shown that both energy and stochasticity contribute to patterns. Monte Carlo simulations reveal that short-range forces between dislocations lead to wall-like structures, while long-range forces control the wall thickness. Perturbation simulations demonstrate that persistent, low-density regions form when the network is perturbed over sufficient deformation. These findings suggest a two-stage process where stochasticity forms low-density regions, which then lead to confined walls through local energy minimization.

Abstract Movement screens are widely used to identify aberrant movement patterns in hopes of decreasing risk of injury, identifying talent, and/or improving performance. Motion capture data can provide quantitative, objective feedback regarding movement patterns. The dataset contains three-dimensional (3D) motion capture data of 183 athletes performing mobility tests (ankle, back bend, crossover adduction, crossover rotation, elbows, head, hip turn, scorpion, shoulder abduction, shoulder azimuth, shoulder rotation, side bends, side lunges and trunk rotation) and stability tests (drop jump, hop down, L-cut, lunge, rotary stability, step down and T-balance) bilaterally (where applicable), the athletes’ injury history, and demographics. All data were collected at 120 Hz or 480 Hz using an 8-camera Raptor-E motion capture system with 45 passive reflective markers. A total of 5,493 trials were pre-processed and included in .c3d and .mat formats. This dataset will enable researchers and end users to explore movement patterns of athletes of varying demographics from different sports and competition levels; develop objective movement assessment tools; and gain new insights into the relationships between movement patterns and injury.

Abstract Introduction Atopic dermatitis (AD)—a chronic inflammatory skin disease characterized by intense itching—can have a detrimental impact on quality of life (QoL). We report results of a quantitative assessment of pediatric patient, caregiver, and physician perceptions of AD burden in children and adolescents. Methods Pediatric patients (aged 6–11 [children] or 12–17 [adolescents] years) with moderate-to-severe AD, their caregivers, and independent physicians were recruited in 13 countries. Caregivers and their children/adolescents completed an online survey about the impact of AD on 16 key items of patient QoL. Physicians completed surveys on their patients aged 6–11 and 12–17 years. Best–worst scaling was used to rank the importance of the QoL items. Results Overall, 1447 children/adolescents with moderate-to-severe AD (aged 6–11 years: 701; 12–17 years: 746), 1447 caregivers, and 1092 physicians participated. Patients and caregivers in both age groups ranked disturbed sleep as the most important QoL item, followed by feeling ashamed because of AD. Independent physicians ranked feeling ashamed because of AD as the most important QoL item for both age groups, followed by disturbed sleep for those aged 6–11 years and being singled out for those aged 12–17 years. The relative importance of the 16 QoL items to patients was strongly aligned between patients in both age groups and their caregivers, but somewhat less so between patients and physicians. Between-country differences were more apparent in physician- versus patient-/caregiver-reported results. Conclusion The most burdensome QoL items were impact of AD on sleep and feeling ashamed. Caregivers and physicians correctly identified the QoL items most burdensome to patients. However, patient and caregiver perceptions were generally more closely aligned than patient and physician perceptions. Between-country differences in perceptions (particularly for physicians) were observed, probably due to multifactorial reasons, necessitating further evaluation. Video Abstract (MP4 42,877 kb) Infographic

Soldier burden is influenced by the environment, metabolic demands, equipment properties, and psychological stressors; however, much of our knowledge of soldier burden is in the context of body-borne load mass in controlled laboratory environments. Thus, to further our understanding of how all aspects of soldier burden affect the survivability tradespace (i.e., performance, health, and susceptibility to enemy action), field-based motion capture methods are needed. We developed a human activity recognition method using the deep convolutional long short-term memory neural network architecture, trained using a single inertial measurement unit on the upper back, to identify eleven tactical movement patterns commonly performed by soldiers. Using a two-step logical algorithm, real-world constraints are forced, and class labels are expanded to 19 movements. Presented are three models based on Indoor, Section Attack (outdoors), and a General approach. Across all three approaches, we obtained an average accuracy of 90.0%. Further, we used these predictions to calculate meaningful tradespace metrics, which had an excellent agreement with calculations using the true labels. Military leaders and defence scientists can use this approach to quantify tradespace metrics in the field, as a preprocessing tool to supplement other technology, and make data-driven decisions that can help improve performance, decrease susceptibility, and increase overall mission success.

Introduction: The aim of this study is to evaluate treatment patterns, survival outcomes, and factors influencing systemic treatment decisions in adults 80 years and older with NSCLC. Methods: This was a retrospective National Cancer Database study evaluating outcomes in adults aged 80 years and older with advanced NSCLC. Patients were analyzed on the basis of systemic therapy, including none, chemotherapy or immunotherapy (IO) alone, and chemotherapy plus IO (chemotherapy + IO). Median overall survival (OS) was compared using Kaplan-Meier methodology. Hazard ratio with 95% confidence interval (CI) was used to assess differences in outcomes, and OR with 95% CI was used to assess factors contributing to systemic therapy provision. Results: Patients 80 years and older (OR = 1.135 [95% CI: 1.127–1.142], p = 0.000), females (OR = 1.129 [95% CI: 1.085–1.175], p < 0.001), blacks (OR = 1.272 [95% CI: 1.179–1.372], p < 0.001), non-Hispanic whites (OR = 1.210 [95% CI: 1.075–1.362], p = 0.002), and those with increasing Charlson-Deyo Comorbidity Index score (p < 0.001) were less likely to receive systemic therapy. Median OS for no therapy, IO alone, chemotherapy alone, and chemotherapy plus IO was 2.63 (95% CI: 2.57–2.69), 10.68 (95% CI: 9.96–11.39), 12.35 (95% CI: 11.98–12.72), and 14.03 (95% CI: 13.87–14.88) months, respectively. In chemotherapy alone, mean OS was 1.12 months (95% CI: 0.55–1.70) (p < 0.001) longer with multiagent versus single agent. There was no difference between IO plus single agent versus IO plus multiagent chemotherapy (0.67 mo [95% CI −1.18 to 2.54], p = 1.00). Conclusions: Age, comorbidities, patient race, and sex affected systemic therapy provision. Multiagent chemotherapy and chemotherapy plus IO significantly improved survival; with the latter, survival was similar with IO plus single or multiagent chemotherapy.

The outward migration of ommin pigment granules from the bases to the tips of the photoreceptors in response to light has been reported in the retina of several (mostly coastal) squid species. Following exposure to light and then dark conditions, we collected and processed retinal tissue from juvenile specimens of a deep-sea oegopsid squid, Gonatus onyx. We aimed to determine whether the ommin pigment returns to baseline, and to investigate the presence of glutamate neurotransmitter signaling under both dark and light conditions. We confirmed the presence of ommin granules but observed variability in the return of pigment to the basal layer in dark conditions, as well as changes in glutamate distribution. These findings provide support for the migration of retinal ommin pigment granules as a mechanism for regulating incoming light.

Cell spreading and migration play central roles in many physiological and pathophysiological processes. We have previously shown that MFN2 regulates the migration of human neutrophil-like cells via suppressing Rac activation. Here, we show that in mouse embryonic fibroblasts, MFN2 suppresses RhoA activation and supports cell polarization. After initial spreading, the wild-type cells polarize and migrate, whereas the Mfn2-/- cells maintain a circular shape. Increased cytosolic Ca2+ resulting from the loss of Mfn2 is directly responsible for this phenotype, which can be rescued by expressing an artificial tether to bring mitochondria and endoplasmic reticulum to close vicinity. Elevated cytosolic Ca2+ activates Ca2+/calmodulin-dependent protein kinase II, RhoA, and myosin light-chain kinase, causing an overactivation of nonmuscle myosin II, leading to a formation of a prominent F-actin ring at the cell periphery and increased cell contractility. The peripheral actin band alters cell physics and is dependent on substrate rigidity. Our results provide a novel molecular basis to understand how MFN2 regulates distinct signaling pathways in different cells and tissue environments, which is instrumental in understanding and treating MFN2-related diseases.

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.

Reason for doing the work Plant biomass is a commonly used metric to assess agricultural health and productivity. Removing plant material is the most accurate method to estimate plant biomass, but this approach is time consuming, labor intensive, and destructive. Previous attempts to use indirect methods to estimate plant biomass have been limited in breadth and/or have added complexity in data collection and/or modeling. A cost-effective, quick, accurate, and easy to use and understand approach is desirable for use by scientists and growers. Objectives An indirect method for estimating plant biomass using a drop-plate meter was explored for use in broad array of crop systems. Methods Drop-plate data collected by more than 20 individuals from 16 crop types on 312 farms across 15 states were used to generate models to estimate plant biomass among and within crop types. Results A linear model using data from all crop types explained approximately 67% of the variation in plant biomass overall. This model performed differently among crop types and stand heights, which was owed to differences among sample sizes and farming between annual and perennial systems. Comparatively, the model using the combined dataset explained more variance in biomass than models generated with commodity specific data, with the exception of wheat. Conclusions The drop-plate approach described here was inexpensive, quick, simple, and easy to interpret, and the model generated was robust to error and accurate across multiple crop types. The methods met all expectations for a broad-use approach to estimating plant biomass and are recommended for use across all agroecosystems included in this study. While it may be useful in crops beyond those included, validation is suggested before application.

Abstract Information on fortifiable food consumption is essential to design, monitor and evaluate fortification programmes, yet detailed methods like 24‐h recalls (24HRs) that provide such data are rarely conducted. Simplified questionnaire‐based methods exist but their validity compared with 24HRs has not been shown. We compared two simplified methods (i.e., a household food acquisition and purchase questionnaire [FAPQ] and a 7‐day semiquantitative food frequency questionnaire [SQ‐FFQ]) against 24HRs for estimating fortifiable food consumption. We assessed the consumption of fortifiable wheat flour and oil using a FAPQ and, for wheat flour only, a 7‐day SQ‐FFQ and compared the results against 24HRs. The participants included children 12−18 months (n = 123) and their mothers 18−49 years selected for a study assessing child vitamin A intake and status in Mandaluyong City, Philippines. For fortifiable wheat flour, the FAPQ estimated considerably lower mean intakes compared to 24HRs for children and mothers (2.2 vs. 14.1 g/day and 5.1 vs. 42.3 g/day, respectively), while the SQ‐FFQ estimated slightly higher mean intakes (15.7 vs. 14.1 g/day and 51.5 vs. 42.3 g/day, respectively). For fortifiable oil, the FAPQ estimated considerably higher mean intakes compared to 24HRs for children and mothers (4.6 vs. 1.8 g/day and 12.5 vs. 6.1 g/day, respectively). The SQ‐FFQ, but not the FAPQ, generated useful information on fortifiable food consumption that can inform fortification programme design and monitoring decisions in the absence of more detailed individual‐level data. Potential adaptations to improve the FAPQ, such as additional questions on foods prepared away from home and usage patterns, merit further research.

The objective of this research was to investigate the influence of beef hot carcass weight (HCW) on consumer sensory attributes. Beef carcasses (n = 116) were selected based on the USDA quality grade and HCW. Lightweight (LW; 296–341 kg), middleweight (MW; 386–432 kg), or heavyweight (HW; 466–524 kg) carcasses with USDA Choice (LC) or USDA Select (SEL) quality grades were used in this study. Carcasses were tracked through fabrication and the semitendinosus, chuck roll, and strip loin were collected and fabricated into eye of round, Denver cut, and strip loin steaks, respectively, for consumer sensory evaluation. USDA Select MW Denver cut steaks had increased overall liking and texture liking scores and were more tender and juicier than the SEL LW steaks (p ≤ 0.02). USDA Select MW strip loin steaks had increased overall and flavor liking scores and were more tender than the SEL LW steaks (p ≤ 0.02). USDA Choice MW eye of round steaks had increased overall, flavor, and texture liking scores and were juicier than the LW eye of round steaks (p ≤ 0.04). The steaks evaluated in this study were differentially impacted by HCW and little to no clear pattern of effects could be determined across cut or quality grade. Additional research is needed to determine the most acceptable HCW from a consumer perspective.

The outcome of bacterial infection management relies on prompt diagnosis and effective treatment, but conventional antimicrobial susceptibility testing can be slow and labor-intensive. Therefore, this study aims to predict phenotypic antimicrobial susceptibility of selected beta-lactam antimicrobials in the bacteria of the family Enterobacteriaceae from different beta-lactamase resistance genotypes. Using human datasets extracted from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program conducted by Pfizer and retail meat datasets from the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS), we used a robust or weighted least square multivariable linear regression modeling framework to explore the relationship between antimicrobial susceptibility data of beta-lactam antimicrobials and different types of beta-lactamase resistance genes. In humans, in the presence of the blaCTX-M-1, blaCTX-M-2, blaCTX-M-8/25, and blaCTX-M-9 groups, MICs of cephalosporins significantly increased by values between 0.34–3.07 μg/mL, however, the MICs of carbapenem significantly decreased by values between 0.81–0.87 μg/mL. In the presence of carbapenemase genes (blaKPC, blaNDM, blaIMP, and blaVIM), the MICs of cephalosporin antimicrobials significantly increased by values between 1.06–5.77 μg/mL, while the MICs of carbapenem antimicrobials significantly increased by values between 5.39–67.38 μg/mL. In retail meat, MIC of ceftriaxone increased significantly in the presence of blaCMY-2, blaCTX-M-1, blaCTX-M-55, blaCTX-M-65, and blaSHV-2 by 55.16 μg/mL, 222.70 μg/mL, 250.81 μg/mL, 204.89 μg/mL, and 31.51 μg/mL respectively. MIC of cefoxitin increased significantly in the presence of blaCTX-M-65 and blaTEM-1 by 1.57 μg/mL and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of cefoxitin increased by an average of 8.66 μg/mL over 17 years. Compared to E. coli isolates, MIC of cefoxitin in Salmonella enterica isolates decreased significantly by 0.67 μg/mL. On the other hand, MIC of ceftiofur increased in the presence of blaCTX-M-1, blaCTX-M-65, blaSHV-2, and blaTEM-1 by 8.82 μg/mL, 9.11 μg/mL, 8.18 μg/mL, and 1.04 μg/mL respectively. In the presence of blaCMY-2, MIC of ceftiofur increased by an average of 10.20 μg/mL over 14 years. The ability to predict antimicrobial susceptibility of beta-lactam antimicrobials directly from beta-lactamase resistance genes may help reduce the reliance on routine phenotypic testing with higher turnaround times in diagnostic, therapeutic, and surveillance of antimicrobial-resistant bacteria of the family Enterobacteriaceae.

Grassland ecosystems of the Northern Plains have changed substantially since European settlement began in the latter half of the 19th century. This has led to significant changes to the dung-dwelling arthropod community in the region. As humans continue to modify large portions of the landscape, inventories of ecologically significant communities are important to collect in order to monitor the long-term effects of anthropogenic biomes. We conducted a survey of the arthropod community dwelling in cattle dung from 40 pastures extending from northeast South Dakota to central North Dakota during the 2019 and 2020 grazing seasons. In sum, 51,283 specimens were collected from 596 dung pats, comprising a community of 22 orders. Coleoptera, Diptera, and Hymenoptera contributed to the majority (94.5%) of the community abundance. The mean pest abundance was low per pat (0.43 adult pests/pat), with 80% of the pats not containing any adult pest. Ecologically beneficial dung-feeding beetles, predators, and parasitoids were abundant in the region, but it was an inconsistent community, which may hinder ecosystem services. This highlights the need for future work to understand the mechanisms to increase the consistency of dung pat colonization for improved consistency of ecosystem services in the region.

Objective To determine the potential risk factors associated with having COVID-19 among unvaccinated pregnant and non-pregnant women.Design A multicentre prospective cohort study among eligible women in Metro Manila, Philippines, from 2020 to 2022.Setting Five national and local hospital research sites altogether recruited and screened 500 consenting eligible individuals.Participants Pregnant and non-pregnant participants meeting the eligibility criteria were admitted for a reverse-transcription PCR determination of SARS-CoV-2, pregnancy testing and ultrasound, and an interview with an administered questionnaire.Exposures Primary exposure was pregnancy; secondary exposures involve sociodemographic, lifestyle and obstetric-gynaecologic factors.Outcome measure Outcome being measured was COVID-19 status.Results The significant COVID-19 risk factors were: pregnancy (PR=1.184, 95% CI 1.096, 1.279), having a white-collar job (PR=1.123, 95% CI 1.02, 1.235), travelling abroad (PR=1.369, 95% CI 1.083, 1.173) and being infected by at least one vaccine-preventable disease (VPD) (PR=1.208, 95% CI 1.113, 1.310). Protective factors included having graduate-level education (PR=0.787, 95% CI 0.649, 0.954), immunisation against a VPD (PR=0.795, 95% CI 0.733, 0.862) and practising contraception (PR=0.889, 95% CI 0.824, 0.960).Conclusion This study is the first in the country to determine the risks influencing COVID-19 infection among unvaccinated pregnant and non-pregnant women. Pregnancy is a significant risk for COVID-19 among women in Metro Manila. Educational attainment and positive health behaviours seem to confer protection. Occupations and activities that increase the frequency of interactions, as well as history of communicable diseases may predispose women to COVID-19. Further studies are needed to elucidate the development of the disease in pregnant women, including the maternal and neonatal effects of COVID-19 via potential vertical mechanisms of transmission.

In this article, we report the first ever antenna array with >90% transparency that is intended for 5G networks for smart cities. This level of transparency is achieved by using Gallium-doped Zinc Oxides. The array designed and tested is for sub-6GHz 5G and operates at 5.8GHz. This seamless design allows such arrays to be integrated into windows of buildings within the smart city to provide consistent network coverage. The phased array has good gain and scanning characteristics as presented below. We have also included a discussion regarding gain and beam steering capabilities in comparison to similar arrays made of conventional copper and RF substrates. This study presents the comparison of two antenna arrays, one constructed from copper antenna elements (Simulated operational band from 5.67 GHz to 6.62 GHz, 7.6% bandwidth, and gain of 2.18 dBi) and one constructed from GZO antenna elements (Simulated operational band from 2.8 GHz to 10 GHz, 112.5% bandwidth, approximately 8% efficiency, and a gain of −10.87 dBi). Both element designs have a 1.5cm by 1.5cm footprint. The results show that a 4x1 array of GZO elements will increase the gain to 0.34 dBi from a gain of −10.87 dBi of a thin film, GZO antenna element. In addition, over 90% transparency allows window integration without obstructing the view. The techniques described in this article also can be used to integrate such arrays in glasses and other transparent materials for various IoT applications.

ObjectiveThe 2-year incidence of brain metastases (BrMs) in stage III non-small lung cell cancer (NSCLC) has been estimated to be around 30%. However, recent clinical trials have demonstrated considerably lower BrMs rates in this patient population. In this study, we aimed to review the real-world incidence, surveillance, and treatment patterns of BrMs in stage III NSCLC.Materials and methodsUsing a retrospective single-center study design, we identified patients with stage III NSCLC who received radiation with curative intent over a 10-year period. Outcome variables included BrMs incidence, overall survival (OS), and survival from date of BrMs. Additionally, we assessed patterns of BrMs surveillance in stage III NSCLC and treatment.ResultsWe identified a total of 279 stage III NSCLC patients, of which 160 with adequate records were included in the final analyses [adenocarcinoma (n = 96), squamous cell carcinoma (n = 53), other histology subtype (n = 11)]. The median OS for the entire cohort was 41 months (95% CI, 28-53), while the median time from BrMs to death was 19 months (95% CI, 9-21). Twenty-three patients (14.4%) received planned surveillance brain MRIs at 6, 12, and 24 months after completion of treatment. The remaining 137 patients (85.6%) received brain MRIs at systemic recurrence (restaging) or when neurologically symptomatic. A total of 37 patients (23%) developed BrMs, with a 2-year cumulative BrMs incidence of 17% (95% CI, 11-23). A higher incidence of BrMs was identified in patients with adenocarcinoma relative to those with squamous cell carcinoma (p < 0.01). Similarly, a higher 2-year BrMs incidence was observed in patients who received planned surveillance brain MRI relative to those who did not, although statistical significance was not reached. Stereotactic radiosurgery (SRS) treated 29 of BrMs patients (78.4%) and was preferred over WBRT, which treated only 3 patients (8.1%).ConclusionsAt our center, BrMs incidence in stage III NSCLC patients was lower than historically reported but notably higher than the incidence described in recent clinical trials. Routine BrMs surveillance potentially allows earlier detection of asymptomatic BrMs. However, asymptomatic BrMs were mostly detected on restaging MRI at the time of recurrence.

Background The goal of this study was to determine if 10-min of anodal transcranial direct current stimulation (a-tDCS) to the motor cortex (M1) is capable of modulating quadriceps isometric maximal voluntary contraction (MVC) force or fatigue endurance contralateral or ipsilateral to the stimulation site. Methods In a randomized, cross-over design, 16 (8 females) individuals underwent two sessions of a-tDCS and two sham tDCS (s-tDCS) sessions targeting the left M1 (all participants were right limb dominant), with testing of either the left (ipsilateral) or right (contralateral) quadriceps. Knee extensor (KE) MVC force was recorded prior to and following the a-tDCS and s-tDCS protocols. Additionally, a repetitive MVC fatiguing protocol (12 MVCs with work-rest ratio of 5:10-s) was completed following each tDCS protocol. Results There was a significant interaction effect for stimulation condition x leg tested x time [F(1,60) = 7.156, p = 0.010, ηp2 = 0.11], which revealed a significant absolute KE MVC force reduction in the contralateral leg following s-tDCS (p < 0.001, d = 1.2) and in the ipsilateral leg following a-tDCS (p < 0.001, d = 1.09). A significant interaction effect for condition x leg tested [F(1,56) = 8.12, p = 0.006, ηp2 = 0.13], showed a significantly lower ipsilateral quadriceps (to tDCS) relative MVC force with a-tDCS, versus s-tDCS [t(15) = -3.07, p = 0.016, d = -0.77]. There was no significant difference between the relative contralateral quadriceps (to tDCS) MVC force for a-tDCS and s-tDCS. Although there was an overall significant [F(1,56) = 8.36, p < 0.001] 12.1% force decrease between the first and twelfth MVC repetitions, there were no significant main or interaction effects for fatigue index force. Conclusion a-tDCS may be ineffective at increasing maximal force or endurance and instead may be detrimental to quadriceps force production.

The Arp2/3 complex is an actin nucleator with well-characterized activities in cell morphogenesis and movement, but its roles in nuclear processes are relatively understudied. We investigated how the Arp2/3 complex affects genomic integrity and cell cycle progression using mouse fibroblasts containing an inducible knockout (iKO) of the ArpC2 subunit. We show that permanent Arp2/3 complex ablation results in DNA damage, the formation of cytosolic micronuclei, and cellular senescence. Micronuclei arise in ArpC2 iKO cells due to chromatin segregation defects during mitosis and premature mitotic exits. Such phenotypes are explained by the presence of damaged DNA fragments that fail to attach to the mitotic spindle, abnormalities in actin assembly during metaphase, and asymmetric microtubule architecture during anaphase. In the nuclei of Arp2/3-depleted cells, the tumor suppressor p53 is activated and the cell cycle inhibitor Cdkn1a/p21 mediates a G1 arrest. In the cytosol, micronuclei are recognized by the DNA sensor cGAS, which is important for stimulating a STING- and IRF3-associated interferon response. These studies establish functional requirements for the mammalian Arp2/3 complex in mitotic spindle organization and genome stability. They also expand our understanding of the mechanisms leading to senescence and suggest that cytoskeletal dysfunction is an underlying factor in biological aging.

Lawsonella clevelandensis is a fastidious Gram-positive, partially acid-fast, anaerobic, catalase positive bacterium that has been reported to be a rare cause of abdominal, breast, spinal, and liver abscesses. Here, three L. clevelandensis vascular graft infections (VGIs) and cardiac infections are reported.

Majocchi’s granuloma (MG) is an uncommon form of deep fungal folliculitis that is most frequently caused by dermatophytes. Here, we present a case of facial MG.

(4-(Adamantan-1-yl)-1-(isopropyl)-1H-imidazol-2-yl)methanol was prepared through a five-step process starting from commercially available 1-acetyladamantane. Each step proceeded in moderate-to-excellent yields and the overall yield across five steps was 28%. The compound was identified and characterized by 1H and 13C{1H} NMR, high-resolution mass spectroscopy, and elemental analysis. This compound and its derivatives have the potential to be used as precursors to the synthesis of biomimetic chelating ligands.

Metalloenzymes make extensive use of manganese centers for oxidative catalysis, including water oxidation; the need to develop improved synthetic catalysts for these processes has long motivated the development of bioinspired manganese complexes. Herein, we report a series of bpy-(imidazole)n (n = 1 or 2) (bpy = 2,2′-bipyridyl) ligands and their Mn2+ complexes. Four Mn2+ complexes are structurally characterized using single-crystal X-ray diffraction, revealing different tridentate and tetradentate ligand coordination modes. Cyclic voltammetry of the complexes is consistent with ligand-centered reductions and metal-centered oxidations, and UV-vis spectroscopy complemented by TD-DFT calculations shows primarily ligand-centered transitions with minor contributions from charge-transfer type transitions at higher energies. In solution, ESI-MS studies provide evidence for ligand reorganization, suggesting complex speciation behavior. The oxidation of the complexes in the presence of water is probed using cyclic voltammetry, but the low stability of the complexes in aqueous solution leads to decomposition and precludes their ultimate application as aqueous electrocatalysts. Possible reasons for the low stability and suggestions for improvement are discussed.

Objective: We describe a rare case of profound subcutaneous insulin resistance (SIR) presumed due to a paraneoplastic process caused by pancreatic adenocarcinoma that improved with intravenous insulin and tumor resection. Methods: An 80-year-old man with previously well-controlled type 2 diabetes mellitus had worsening glycemic control (hemoglobin A1C increase of 6.5% to 8.6% over 4 months) following a recent diagnosis of pancreatic adenocarcinoma. His blood glucose was uncontrolled at 600 mg/dL despite rapid up-titration of a subcutaneous basal-bolus insulin regimen totaling 1000 units/d. Extensive evaluation of insulin resistance including insulin antibodies and anti-insulin receptor antibodies was negative. Due to clinical deterioration, the patient underwent pancreaticoduodenectomy before the completion of neoadjuvant chemotherapy. The patient received intravenous insulin before surgery, which resulted in rapid improvement in glycemic control. The patient’s blood glucose normalized, and he was maintained on metformin monotherapy following pancreaticoduodenectomy. Results: This patient had evidence of SIR in the setting of pancreatic adenocarcinoma. SIR was likely a paraneoplastic process as glycemic control improved after tumor resection. Interestingly, the patient did not have hyperinsulinemia but rather evidence of β-cell dysfunction, which highlights the possibility of exogenous insulin resistance. Conclusion: Paraneoplastic processes due to pancreatic adenocarcinoma can cause SIR, marked by profound hyperglycemia and deteriorating functional status. It is, therefore important to recognize this rare syndrome and appropriately escalate to a higher level of care and consider proceeding with tumor resection.

ABSTRACT Staphylococcus epidermidis is implicated in a multitude of human infections and is one of the major causes of clinical infections in hospitals, especially at surgical sites and on indwelling medical devices, such as orthopedic implants. These infections are especially dangerous because of the S. epidermidis propensity to form biofilms, which increases resistance to antibiotics and the natural immune response. This study investigated pulsed electromagnetic fields (PEMF) as a potential treatment to combat such infections, as PEMF exposure was expected to disrupt the electrostatic forces that adhere staphylococcal cells to surfaces and to one another. To test the effect of PEMF on biofilms, S. epidermidis cultures were exposed to PEMF at various durations either during the growth phase or after a full biofilm had formed. In addition, cells were exposed to PEMF and concomitant antibiotic treatment. Biofilm viability was quantified by both crystal violet and alamarBlue assays and scanning electron microscopy. The results demonstrated that PEMF significantly inhibited biofilm formation and disrupted preformed biofilms in vitro while also showing synergistic biofilm inhibition when combined with antibiotics. These combined results indicate that PEMF should be considered a promising novel technique for treating S. epidermidis biofilm infections and undergo further testing in vivo. IMPORTANCE Antibiotic resistance and biofilm infections are major issues in health care because of the lack of a successful treatment modality and poor patient outcomes. These infections are a particular issue following orthopedic surgery or trauma wherein an infection may form on an orthopedic implant or patient’s bone. The presented study demonstrates that pulsed electromagnetic fields may be a promising novel treatment for such infections and can overcome the medical challenges presented by biofilm formation. Furthermore, the effects demonstrated are even greater when combining pulsed electromagnetic field therapy with traditional antibiotics.