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Detection of metallo-?-lactamase (MBL) is crucial in the management and control of difficult to treat infections. This study aims to determine the prevalence of MBL – producing Gram-negative bacilli among imipenem-resistant multi-drug resistant (MDR) clinical isolates. A total of 224 consecutive MDR Gram-negative bacilli consisting of Escherichia coli (78), Klebsiella species (64), Proteus species (40) and Pseudomonas aeruginosa (40) were used for this study. Imipenem disc susceptibility test was performed on all isolates and MBL detection was performed on imipenem-resistant isolates using standard techniques. Of the 224 MDR isolates tested, 37 (16.52%) were imipenem resistant and the prevalence of this resistant isolates was significantly higher in Ps. aeruginosa (35.00%) compared to others (P = 0.005). Among, the imipenem-resistant isolates, the prevalence of MBL production was highest in Ps. aeruginosa (14.29%) followed by Escherichia coli (11.11%), Klebsiella species (10.00%) and Proteus species (0%). However, the difference in prevalence was not statistically significant (P = 0.8807). Conclusively, Ps. aeruginosa was the most prevalent microorganism that was resistant to imipenem. An overall prevalence of 10.81% of MBL producers was observed among imipenem-resistant microbial isolates. Measures to control and prevent the spread of MBL producing and imipenem-resistant microbial isolates are advocated.

Coronavirus-associated coagulopathy (CAC) is a morbid and lethal sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CAC results from a perturbed balance between coagulation and fibrinolysis and occurs in conjunction with exaggerated activation of monocytes/macrophages (MO/Mφs), and the mechanisms that collectively govern this phenotype seen in CAC remain unclear. Here, using experimental models that use the murine betacoronavirus MHVA59, a well-established model of SARS-CoV-2 infection, we identify that the histone methyltransferase mixed lineage leukemia 1 (MLL1/KMT2A) is an important regulator of MO/Mφ expression of procoagulant and profibrinolytic factors such as tissue factor (F3; TF), urokinase (PLAU), and urokinase receptor (PLAUR) (herein, “coagulopathy-related factors”) in noninfected and infected cells. We show that MLL1 concurrently promotes the expression of the proinflammatory cytokines while suppressing the expression of interferon alfa (IFN-α), a well-known inducer of TF and PLAUR. Using in vitro models, we identify MLL1-dependent NF-κB/RelA–mediated transcription of these coagulation-related factors and identify a context-dependent, MLL1-independent role for RelA in the expression of these factors in vivo. As functional correlates for these findings, we demonstrate that the inflammatory, procoagulant, and profibrinolytic phenotypes seen in vivo after coronavirus infection were MLL1-dependent despite blunted Ifna induction in MO/Mφs. Finally, in an analysis of SARS-CoV-2 positive human samples, we identify differential upregulation of MLL1 and coagulopathy-related factor expression and activity in CD14+ MO/Mφs relative to noninfected and healthy controls. We also observed elevated plasma PLAU and TF activity in COVID-positive samples. Collectively, these findings highlight an important role for MO/Mφ MLL1 in promoting CAC and inflammation.

This study examined the costs and returns of rainy season rice production in Birnin Gwari local government area of Kaduna state. Two stage sampling procedure was employed to select forty-eight respondents (48) respondents for the study. Primary data were collected using structured questionnaire with the help of well-trained enumerators. Data were analyzed using descriptive statistics, Gross margin analysis and profitability ratios. Results revealed that the respondents were predominantly male (60.4%) and most (52.1%) were married. 25% had primary education,45.8% secondary education, and 12.5% tertiary education. The mean age for the households’ head was 33 years and the mean household size was 7 persons per household. The mean farming experience and annual farm income of the respondents were 17 years and ₦32,238 respectively. The average variable cost incurred per hectare was estimated to be N122,988 while the total cost of production was put at N 139,309. Gross revenue of N 257,000 was generated with a gross margin of N 134,012 and a net farm income of N 117,691. The profitability ratios of BCR=1.84, ESR=0.13, ROR=0.84, and GR=0.5, indicated that rainy season rice farming is highly profitable in the study area. The study therefore recommended that consistent government policies that would favor increase in paddy production, market information, extension service delivery, input subsidization and credit facilities be implemented.

We report uptake capacities and transport diffusivities, D, for each of eight linear alkanes (ranging from C5 to C16) in quartz crystal-supported films of solvent-evacuated ZIF-8. Analyses of the alkane uptake profiles revealed that the transport dynamics are governed by guest diffusion through metal-organic framework (MOF) (ZIF-8) crystallites rather than by rates of entry into films at the MOF/vapor interface. The obtained diffusivities range from just over 10-18 m2/s to just under 10-14 m2/s. Notably, minimum cross-sectional widths for all guests exceed the crystallographically measured width of ZIF-8's largest apertures and imply consistently with previous experimental and computational studies that apertures expand to accommodate guest uptake. On average, each additional carbon decreases the transport diffusivity of an alkane by twofold. Closer examination, however, reveals an odd-even effect such that linear alkanes having even numbers of carbons diffuse more rapidly than alkanes featuring one more or one less carbon atom. Thus, ZIF-8's differentiation of transport diffusivities for pairs of alkanes differing in length by only one carbon atom can be significantly greater than the aforementioned factor of 2. Elucidation of the microscopic basis for the odd-even behavior, however, awaits the outcome of molecular dynamics calculations that are beyond the scope of the present study. For compact, solvothermally prepared films, guest transport is dominated by 1D diffusion from the film/vapor interface and toward the underlying quartz crystal. For much lower density, electrophoretically deposited (EPD) films, crystallites behave nearly independently, and guest transport can be adequately modeled by assuming rapid permeation of macroscopic voids between crystallites, followed by entry and rate-limiting radial diffusion into isolated crystallites. One consequence is that EPD films can be much more rapidly infiltrated by molecular guests than can compact, solvothermally grown films. The combined results have potentially favorable implications for the development of kinetic separation schemes for closely related analytes.

Despite the scale up of quality-assured Tuberculosis diagnostic and treatment strategies over the years, case detection rate remains a serious challenge globally and particularly in Nigeria. Integrated service delivery is essential to addressing some of the challenges, but it's often neglected especially in low income settings. Recognizing these limitations, a 27-months retrospective review of all presumptive Pulmonary Tuberculosis cases sent to the directly observed short course treatment centre of Benue State University Teaching Hospital, a tertiary health institution in north central Nigeria was conducted to assess the source of referrals and diagnostic processes including outcome of the tests. Chi- square (χ2) test was used for test of association between the intra-facility linkages/referrals system and the tuberculosis case detection rate, with statistical significance set at p-value of ≤5%. There were 918 presumptive Tuberculosis cases with male to female ratio (M: F) of 1:1.3. The mean age of patients was 41.0.0 ±18.4 years. Majority (33.7%, n=) of the referrals were from general outpatient department of the hospital, followed by sexually transmitted infection clinic (26.0%) and Paediatrics department (1.6%, n=). The diagnostic positive rate was 145(15.8%). Overall, 295(32.2%) did not collect their results, of these 76(25.8%) were positive and 219(74.2%) were negative. The relationship between the missed cases and the weak intra-facility referral linkages was statistically significant (p=0.000). The hospital management should consider the engagement of all relevant health care providers on efficient two-way referral system towards ensuring adequate Tuberculosis case notification and prompt treatment.

Background: Research studies abound on substance use among healthcare workers (HCWs) in the western world, but a paucity of such information is the case in developing countries. Objectives: To determine the prevalence of substance use among HCWs in a Nigerian tertiary hospital and the variety of substances commonly used. Method: A cross-sectional study was conducted among 380 HCWs selected across 4 professional cadres by stratified random sampling method. Results: About 85.5% of the respondents were past and/or current users of substances or substance-containing food items. Out of the 325 respondents who had ever used substances before, 208 (64%) were current users- these represented 54.7% of the whole. Coffee, alcohol and kolanuts were most frequently used. Diazepam was the least used. Gender was a statistically significant determinant of substance use (p

Objectives: Coronavirus associated coagulopathy (CAC) is postulated to be driven by systemic macrophage activation after SARS-CoV-2 infection and presents with elevated risk of thrombogenesis and hyperfibrinolysis. Previous work shows that the histone methyltransferase KMT2A/MLL1 is a key mediator of inflammatory signaling in monocytes and macrophages (Mo/Mϕs). In this study, we sought to identify the regulation of factors important in CAC by MLL1. Methods: Mice with myeloid specific knockout of MLL1 (Cre+) and littermate controls (Cre-) underwent intranasal inoculation of 2 x 10 5 pfu of the murine coronavirus MHVA59, an established model which phenocopies SARS-CoV-2 infection. Splenic Mϕs (surrogate for circulating Mo/Mϕs) were isolated and RNA and protein levels of urokinase (Plau; profibrinolytic), urokinase receptor (Plaur; profibrinolytic), and tissue factor (F3/TF; procoagulant) were analyzed using qRT-PCR and ELISA, respectively. Thromboelastography (TEG) on whole blood and urokinase activity assays from mouse plasma were performed. Urokinase and TF activity assays were performed on plasma from human samples. Results: RNA (top panel) and protein (bottom) levels of Plau, Plaur, and F3 were suppressed in the Splenic Mϕs harvested from sham (intranasal PBS) and infected Cre+ animals (white bars) compared to Splenic Mϕs harvested from Cre- animals (blue bars; Fig. 1A). Cre- mice displayed a shortened R-time (reaction time) as measured by TEG (Fig. 1B) and elevated plasma urokinase activity levels (not shown). Hospitalized COVID-positive patients (hCOV+) displayed elevated plasma urokinase and TF activity levels (Fig. 1C). Conclusions: We identify a role for MLL1 for basal expression and for coronavirus-mediated induction of factors important for fibrinolysis and coagulation in murine Mo/Mϕs and in driving coagulopathy. Our results suggest that MLL1 blockade may be an attractive strategy to combat coronavirus associated coagulopathy.

Plasmacytoid dendritic cells (pDCs) are first responders to tissue damage and interact with wound CD4 T-cells to orchestrate tissue repair. In diabetes, the role of pDCs and their subsequent influence on wound CD4 T-cells and inflammation during tissue repair is unknown. Using human diabetic wound single cell sequencing, we identified that human wound CD4 T cells are primarily the Th17 phenotype. Thus, we hypothesized that pDCs in the wounds may regulate this inflammatory T cell phenotype, contributing to chronic inflammation. Although pDCs exist in low numbers in the wounds, we isolated wound pDCs from diabetic and control mice and examined them for inflammatory cytokine expression. We found that diabetic pDC produced significantly more IL6 (amongst other inflammatory cytokines) compared to controls. This is important as IL6 has been shown to skew CD4 T-cells towards a Th17 phenotype in tissues. Upon co-culture of diabetic pDCs with naïve CD4 T-cells, a significant increase in Th17 cells was observed by intracellular flow cytometry analysis. In order to examine the increased IL6 from diabetic pDCs we isolated diabetic and control wound pDCs and performed an epigenetic superarray. We identified that histone demethylase Jarid1C was significantly decreased in diabetic pDCs compared to controls. We then isolated diabetic pDCs and performed a ChIP analysis on the IL6 NFkB binding sites in the promoter and identified an increase in tri-methylated lysine 4 on histone 3 (H3K4me3), a marker regulated by Jarid 1C and consistent with increased transcription of IL6. Taken together, this data suggests that in diabetes, pDCs are epigenetically altered to produce increased IL6 and contribute to increased Th17 and inflammation in diabetic wounds.

Macrophage plasticity is critical for normal tissue repair following injury. In pathologic states such as diabetes, macrophage plasticity is impaired, and macrophages remain in a persistent proinflammatory state; however, the reasons for this are unknown. Here, using single-cell RNA sequencing of human diabetic wounds, we identified increased JMJD3 in diabetic wound macrophages, resulting in increased inflammatory gene expression. Mechanistically, we report that in wound healing, JMJD3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 signaling. However, in the diabetic state, we found that IL-6, a cytokine increased in diabetic wound tissue at later time points post-injury, regulates JMJD3 expression in diabetic wound macrophages via the JAK1,3/STAT3 pathway and that this late increase in JMJD3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an H3K27me3 mechanism. Interestingly, RNA sequencing of wound macrophages isolated from mice with JMJD3-deficient myeloid cells (Jmjd3f/fLyz2Cre+) identified that the STING gene (Tmem173) is regulated by JMJD3 in wound macrophages. STING limits inflammatory cytokine production by wound macrophages during healing. However, in diabetic mice, its role changes to limit wound repair and enhance inflammation. This finding is important since STING is associated with chronic inflammation, and we found STING to be elevated in human and murine diabetic wound macrophages at late time points. Finally, we demonstrate that macrophage-specific, nanoparticle inhibition of JMJD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and STING. Taken together, this work highlights the central role of JMJD3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds.

Macrophages are white blood cells with diverse functions contributing to a healthy immune response as well as the pathogenesis of cancer, osteoarthritis, atherosclerosis, and obesity. Due to their pleiotropic and dynamic nature, tools for imaging and tracking these cells at scales spanning the whole body down to microns could help to understand their role in disease states. Here we report fluorescent and radioisotopic quantum dots (QDs) for multimodal imaging of macrophage cells in vivo, ex vivo, and in situ. Macrophage specificity is imparted by click-conjugation to dextran, a biocompatible polysaccharide that natively targets these cell types. The emission spectral band of the crystalline semiconductor core was tuned to the near-infrared for optical imaging deep in tissue, and probes were covalently conjugated to radioactive iodine for nuclear imaging. The performance of these probes was compared with all-organic dextran probe analogues in terms of their capacity to target macrophages in visceral adipose tissue using in vivo positron emission tomography/computed tomography (PET/CT) imaging, in vivo fluorescence imaging, ex vivo fluorescence, post-mortem isotopic analyses, and optical microscopy. All probe classes exhibited equivalent physicochemical characteristics in aqueous solution and similar in vivo targeting specificity. However, dextran-mimetic QDs provided enhanced signal-to-noise ratio for improved optical quantification, long-term photostability, and resistance to chemical fixation. In addition, the vascular circulation time for the QD-based probes was extended 9-fold compared with dextran, likely due to differences in conformational flexibility. The enhanced photophysical and photochemical properties of dextran-mimetic QDs may accelerate applications in macrophage targeting, tracking, and imaging across broad resolution scales, particularly advancing capabilities in single-cell and single-molecule imaging and quantification.

Objective Venous thromboembolism (VTE) is a common disease with potentially devastating and long-term sequelae, such as pulmonary embolism and post-thrombotic syndrome (PTS). Given the mortality risk, prevalence of VTE, and limited access to diagnostic imaging, clinically relevant biomarkers for diagnosis and prognostication are needed. Therefore, this review aimed to summarize the data on clinically applicable biomarkers that best indicate acute VTE and chronic PTS. Methods We reviewed the medical and scientific literature from 2001 to 2019 for VTE biomarkers. Randomized controlled trials, meta-analyses, and review articles were included. Primary basic research papers with no clinical applicability, opinion papers, institutional guidelines, and case reports were excluded. Results We highlight the diagnostic value of D-dimer alongside other promising biomarkers, including cellular adhesion molecules, P-selectin, cytokines (interleukins 6 and 10), fibrin monomer complexes, and coagulation factors (factor VIII). Conclusions High-sensitivity D-dimer remains the most clinically established VTE biomarker. Current research endeavors are under way to identify more precise biomarkers of VTE and PTS.

A large number of males and females are engaged in the provision of food in Wadata market. Hand hygiene is the cornerstone of infection prevention (IP). When optimally performed, hand hygiene reduces healthcare-associated infections (HAI), spread and antimicrobial resistance (AMR). Poor compliance with hand hygiene practices remains a challenge for IP practitioners all over the world. More than 250 foodborne diseases are caused by bacteria or parasites. This study was conducted using a descriptive cross-sectional study of 138 respondents in Wadata market. Peer-reviewed and pilot tested questionnaires were employed. The questionnaires were classified into four sections namely-socio - demographic characteristics, knowledge on hand hygiene, attitude towards food hygiene and hygiene practices. Data analysis was done using Epi info a software package for statistical analysis version 23. Majority (40.6%) of the respondents were between the ages of 21-30 years. There were more females (80.6%) food vendors than males. Over 65% of the respondents had education above secondary school; and most of them obtained information on hand hygiene from mass media. Over 62% could define hand hygiene correctly while more than 90% had positive attitude towards hand hygiene. The practice level of the respondents of hand hygiene in this study was poor 42.7%. There was significant association between educational status and knowledge of hand hygiene (p

Background Deep venous thrombosis (DVT) in the pediatric population is rare, occurring in about 10 to 14 out of 10,000 pediatric admissions annually, but with serious consequences such as pulmonary embolism and/or post-thrombotic syndrome. There is a dearth of surgical literature regarding this entity, its pathophysiology, its treatment and its long-term sequelae. Methods An extensive search of available surgical and medical literature in Medline, PubMed was obtained by searching terms synonymous with pediatric DVT. Case reports and opinion articles were excluded. Ongoing clinical trials were culled from clinicaltrial.gov by searching for pediatric DVT studies. Institutional guidelines, where available, were included in this summary. Results We provide a clinically relevant summary with the aims of improving prevention, early identification and treatment of pediatric DVT. Conclusions Although rare and frequently with subtle presentations, pediatric DVT can be serious. Early identification and treatment can be instrumental in limiting sequelae and in improving outcomes for these patients.

We report uptake capacities and transport diffusivities

Significance The COVID-19 pandemic has disproportionately affected patients with comorbidities, namely, obesity and type 2 diabetes. Macrophages (Mφs) are a key innate immune cell primarily responsible for the harmful, hyperinflammatory “cytokine storm” in patients that develop severe COVID-19. We describe a mechanism for this Mφ-mediated cytokine storm in response to coronavirus. In response to coronavirus infection, expression of the chromatin-modifying enzyme, SETDB2, decreases in Mφs, leading to increased transcription of inflammatory cytokines. Further, we find SETDB2 is regulated by an interferon beta (IFNβ)/JaK/STAT3 mechanism, and that exogenous administration of IFNβ can reverse inflammation, particularly in diabetic Mφs via an increase in SETDB2. Together, these results suggest therapeutic targeting of the IFNβ/SETDB2 axis in diabetic patients with COVID-19 may decrease pathologic inflammation., COVID-19 induces a robust, extended inflammatory “cytokine storm” that contributes to an increased morbidity and mortality, particularly in patients with type 2 diabetes (T2D). Macrophages are a key innate immune cell population responsible for the cytokine storm that has been shown, in T2D, to promote excess inflammation in response to infection. Using peripheral monocytes and sera from human patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a murine hepatitis coronavirus (MHV-A59) (an established murine model of SARS), we identified that coronavirus induces an increased Mφ-mediated inflammatory response due to a coronavirus-induced decrease in the histone methyltransferase, SETDB2. This decrease in SETDB2 upon coronavirus infection results in a decrease of the repressive trimethylation of histone 3 lysine 9 (H3K9me3) at NFkB binding sites on inflammatory gene promoters, effectively increasing inflammation. Mφs isolated from mice with a myeloid-specific deletion of SETDB2 displayed increased pathologic inflammation following coronavirus infection. Further, IFNβ directly regulates SETDB2 in Mφs via JaK1/STAT3 signaling, as blockade of this pathway altered SETDB2 and the inflammatory response to coronavirus infection. Importantly, we also found that loss of SETDB2 mediates an increased inflammatory response in diabetic Mϕs in response to coronavirus infection. Treatment of coronavirus-infected diabetic Mφs with IFNβ reversed the inflammatory cytokine production via up-regulation of SETDB2/H3K9me3 on inflammatory gene promoters. Together, these results describe a potential mechanism for the increased Mφ-mediated cytokine storm in patients with T2D in response to COVID-19 and suggest that therapeutic targeting of the IFNβ/SETDB2 axis in T2D patients may decrease pathologic inflammation associated with COVID-19.

Wound repair following acute injury requires a coordinated inflammatory response. Type I IFN signaling is important for regulating the inflammatory response after skin injury. IFN-κ, a type I IFN, has recently been found to drive skin inflammation in lupus and psoriasis; however, the role of IFN-κ in the context of normal or dysregulated wound healing is unclear. Here, we show that Ifnk expression is upregulated in keratinocytes early after injury and is essential for normal tissue repair. Under diabetic conditions, IFN-κ was decreased in wound keratinocytes, and early inflammation was impaired. Furthermore, we found that the histone methyltransferase mixed-lineage leukemia 1 (MLL1) is upregulated early following injury and regulates Ifnk expression in diabetic wound keratinocytes via an H3K4me3-mediated mechanism. Using a series of in vivo studies with a geneticall y engineered mouse model (Mll1fl/fl K14cre-) and human wound tissues from patients with T2D, we demonstrate that MLL1 controls wound keratinocyte-mediated Ifnk expression and that Mll1 expression is decreased in T2D keratinocytes. Importantly, we found the administration of IFN-κ early following injury improves diabetic tissue repair through increasing early inflammation, collagen deposition, and reepithelialization. These findings have significant implications for understanding the complex role type I IFNs play in keratinocytes in normal and diabetic wound healing. Additionally, they suggest that IFN may be a viable therapeutic target to improve diabetic wound repair.

Abdominal aortic aneurysms (AAAs) are a life-threatening disease characterized by macrophage infiltration contributing to pathological vascular remodeling. Herein, we demonstrate that the histone demethylase JMJD3 is a critical regulator of inflammation during AAA development and cell-specific inhibition reduces AAA progression., Abdominal aortic aneurysms (AAAs) are a life-threatening disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by macrophage infiltration, and the mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that an epigenetic enzyme, JMJD3, plays a critical role in establishing macrophage phenotype. Using single-cell RNA sequencing of human AAA tissues, we identified increased JMJD3 in aortic monocyte/macrophages resulting in up-regulation of an inflammatory immune response. Mechanistically, we report that interferon-β regulates Jmjd3 expression via JAK/STAT and that JMJD3 induces NF-κB–mediated inflammatory gene transcription in infiltrating aortic macrophages. In vivo targeted inhibition of JMJD3 with myeloid-specific genetic depletion (JMJD3f/fLyz2Cre+) or pharmacological inhibition in the elastase or angiotensin II–induced AAA model preserved the repressive H3K27me3 on inflammatory gene promoters and markedly reduced AAA expansion and attenuated macrophage-mediated inflammation. Together, our findings suggest that cell-specific pharmacologic therapy targeting JMJD3 may be an effective intervention for AAA expansion., Graphical Abstract

Acute axillosubclavian vein thrombosis is a disorder of the anterior thoracic outlet and can be associated with anatomic abnormalities such as occult first rib fracture, abnormal venous or bony anatomy and an abnormally lateral insertion of the costoclavicular ligament. With repetitive overhead activity the subclavian vein sustains continuous damage from mechanical compression. Over time, intraluminal and extraluminal scarring progresses, blood flow becomes impaired and collaterals form to compensate. Acute occlusion results from occlusion of the subclavian vein itself or of the collaterals. Prompt thrombolysis followed by thoracic outlet decompression leads to excellent results. Balloon venoplasty and venous stenting should not be used as primary long-term treatment strategies as untreated mechanical compression will result in recurrent venous occlusion and stent fracture.

The COVID-19 pandemic has had significant ramifications for provider well-being. During these unprecedented and challenging times, one institution's Department of Surgery put in place several important initiatives for promoting the well-being of trainees as they were redeployed to provide care to COVID-19 patients. In this article, the authors describe these initiatives, which fall into 3 broad categories: redeploying faculty and trainees, ensuring provider safety, and promoting trainee wellness. The redeployment initiatives are the following: reframing the team mindset, creating a culture of grace and forgiveness, establishing a multidisciplinary wellness committee, promoting centralized leadership, providing clear communication, coordinating between departments and programs, implementing phased restructuring of the department's services, establishing scheduling flexibility and redundancy, adhering to training regulations, designating a trainee ombudsperson, assessing physical health risks for high-risk individuals, and planning for structured deimplementation. Initiatives specific to promoting provider safety are appointing a trainee safety advocate, guaranteeing personal protective equipment and relevant information about these materials, providing guidance regarding safe practices at home, and offering alternative housing options when necessary. Finally, the initiatives put in place to directly promote trainee wellness are establishing an environment of psychological safety, providing mental health resources, maintaining the educational missions, solidifying a sense of community by showing appreciation, being attentive to childcare, and using social media to promote community morale. The initiatives to carry out the department's strategy presented in this article, which were well received by both faculty and trainee members of the authors' community, may be employed in other departments and even outside the context of COVID-19. The authors hope that colleagues at other institutions and departments, independent of specialty, will find the initiatives described here helpful during, and perhaps after, the pandemic as they develop their own institution-specific strategies to promote trainee wellness.

Macrophages are a primary immune cell involved in inflammation, and their cell plasticity allows for transition from an inflammatory to a reparative phenotype and is critical for normal tissue repair following injury. Evidence suggests that epigenetic alterations play a critical role in establishing macrophage phenotype and function during normal and pathologic wound repair. Here, we find in human and murine wound macrophages that cyclooxygenase 2/prostaglandin E2 (COX-2/PGE2) is elevated in diabetes and regulates downstream macrophage-mediated inflammation and host defense. Using single-cell RNA sequencing of human wound tissue, we identify increased NF-κB–mediated inflammation in diabetic wounds and show increased COX-2/PGE2 in diabetic macrophages. Further, we identify that COX-2/PGE2 production in wound macrophages requires epigenetic regulation of 2 key enzymes in the cytosolic phospholipase A2/COX-2/PGE2 (cPLA2/COX-2/PGE2) pathway. We demonstrate that TGF-β–induced miRNA29b increases COX-2/PGE2 production via inhibition of DNA methyltransferase 3b–mediated hypermethylation of the Cox-2 promoter. Further, we find mixed-lineage leukemia 1 (MLL1) upregulates cPLA2 expression and drives COX-2/PGE2. Inhibition of the COX-2/PGE2 pathway genetically (Cox2fl/fl Lyz2Cre+) or with a macrophage-specific nanotherapy targeting COX-2 in tissue macrophages reverses the inflammatory macrophage phenotype and improves diabetic tissue repair. Our results indicate the epigenetically regulated PGE2 pathway controls wound macrophage function, and cell-targeted manipulation of this pathway is feasible to improve diabetic wound repair., Epigenetic modification of the COX-2/PGE2 pathway modulates diabetic macrophage phenotype, and cell-targeted manipulation improves diabetic tissue repair.

Background Groin wound infections represent a substantial source of patients' morbidity and resource utilization. Definitions and reporting times of groin infections are poorly standardized, which limits our understanding of the true scope of the problem and potentially leads to event under-reporting. Our objective was to investigate the timing and variation of groin wound complications after vascular surgery. Methods We reviewed all patients who underwent vascular surgery with a groin incision at our institution during 2013 (N = 256; 32% female; mean age, 68.8 years). We analyzed patient- and procedure-level variables. Our primary outcome was any groin complication within 180 days. We classified groin-related events as major (hospital readmission or reoperation for groin wound) or minor (wound opened in clinic, initiation of antibiotics specifically for a groin wound, or new groin hematoma or wound drainage). Results The Kaplan-Meier estimated rate of groin complications at 180 days was 23% (n = 53/256); 29 (54%) were major and 24 (46%) were minor. The Kaplan-Meier 30-day event rate was 13% for any complication and only 3% for major complications, indicating that most events occurring within the first 30 days did not require readmission or reoperation. By 180 days, the overall complication rate rose to 23% and the major event rate to 14%, indicating that nearly all complications occurring after 30 days required readmission or reoperation. Those with a groin complication more commonly had tissue loss (23% vs 12%; P = .05), underwent infrainguinal bypass (42% vs 22%; P=.004), had a redo incision (32% vs 18%; P = .03), and had a longer operation (77% vs 65% surgery >200 minutes; P = .07). There were no significant differences in patients' comorbidities, skin closure, dressing type, prosthetic implants, hemostatic agents, or discharge status. Conclusions Whereas >20% of patients suffered a groin complication, nearly half of these events occurred after 30 days. Standardized reporting measures limited to 30-day events or infection definitions that are limited to the need for antibiotic use may misrepresent the true infection rate and thus highlight the need for uniform reporting standards.

Wound repair following acute injury requires a coordinated inflammatory response. Type I interferon (IFN) signaling is important for regulating the inflammatory response post- skin injury. IFN kappa (IFNk), a type I IFN, has recently been found to drive skin inflammation in lupus and psoriasis; however, the role of IFNk in the context of normal or dysregulated wound healing is unclear. Thus, this project explores the role of IFNk in wound repair. Here, we found that IFNk expression is upregulated in keratinocytes early post-injury and is essential for normal tissue repair. Under diabetic conditions, IFNk was decreased in wound keratinocytes, and early inflammation was impaired. Further, we found that the histone methyltransferase mixed lineage leukemia protein-1(MLL1) regulates IFNk expression in diabetic wound keratinocytes via an H3K4me3 mediated mechanism. Using a series of in vivo studies with a genetically engineered mouse model(Mll1fl/flK14cre−) and human wound tissues from patients with T2D, we demonstrate that MLL1 controls wound keratinocyte-mediated IFNk and MLL1 is decreased in T2D keratinocytes. Importantly, we find the administration of IFNk early following injury improves diabetic tissue repair. These findings have significant implications for understanding the complex role type I interferons play in keratinocytes in normal and diabetic wound healing. Additionally, they suggest IFNk may be a viable therapeutic target to improve diabetic wound repair. Supported by MNORC P30-DK089503

Recent work has shown that the cGAS-STING inflammatory pathway is elevated in conditions that are marked by chronic inflammation, such as obesity and diabetes. Using single cell RNA (scRNA) sequencing from human wounds, we show that the Sting gene is increased in diabetic wound macrophages. Histone demethylase JMJD3 specifically demethylates lysine 27 on histone 3 (H3K27me3) - a repressive mark for gene transcription. Using diabetic mice, we note on ChIP analysis, a decrease in the H3K27me3 repressive mark at the STING promoter in diabetic wound macrophages relative to littermate controls, with subsequently enhanced STING protein levels by western blot. Additionally, scRNA from wound macrophages obtained from a novel murine strain deficient in Jmjd3 in myeloid-cell lineages (Jmjd3f/fLyz2Cre+), revealed significantly decreased Sting gene levels. Further, ChIP analysis of H3K27me3 levels at the STING promoter from Jmjd3f/fLyz2Cre+ wound macrophages reveal increased H3K27me3 levels compared to littermate controls, with a concomitant decrease in STING protein as determined by western blot. Mechanistically, we use mRNA, protein and ChIP studies to reveal that in diabetic wound macrophages, IL6 is responsible for increased JMJD3 leading to increased JAK1,3/STAT3 activity and increased STING production. Wound healing curves from diabetic mice locally treated with macrophage-specific nanoparticles against JMJD3 showed significantly improved healing, and decreased STING protein production in these wounds. Taken together, this data highlights a unique epigenetic regulator of STING production in diabetic wound macrophages and provides a viable cell-specific, nanotherapeutic approach to non-healing diabetic wounds. Supported by NIH (F32DK126471), Vascular and Endovascular Surgical Society Resident Research Award

Episiotomy is an incision on the introitus and the perineum to increase pelvic outlet to facilitate childbirth and prevent trauma to fetal and maternal tissues. Episiotomy and perineal laceration may predispose the woman to short and long term complications. The objective of this study was to determine the prevalence of episiotomy and perineal lacerations and their associated risks factors at Benue State University Teaching Hospital, Makurdi, Nigeria. Retrospective data of all women who had spontaneous vagina delivery over a 3 year period with perineal laceration/episiotomy were reviewed. Data was obtained from the records and information on the socio-demographic variables, episiotomies, lacerations and the birth weight of infants. The associated risk factors were recorded using Statistical Package for Social Sciences version 22.Of the 636 vaginal deliveries, 85(13.4%) had lacerations with 65(10.2%) first degree, 19(3.0%) second degree and 1(0.2%) major laceration. Episiotomy rate was 132(20.8%). The mean parity and birth weight of infants were 2.62(SD= ± 1.83) and 3.1 kg (SD= ± 0.767) respectively. The highest number of perineal tears 69(10.8%) were in the lower age group (≤ 30 years). A similar observation was noted in respect of episiotomies which rate however decreased with parity. The relationship between maternal age, parity, booking status, fetal weight and the perineal status at delivery was statistically significant (P≤ 0.05). Episiotomy and perineal laceration rates in our institution were low. The major risk factors were low parity, young maternal age and increasing fetal weight at birth and their presence should be an early warning sign. We advise perineal support for all women during delivery.

Severe orbito-ocular morbidities occur in eye injuries and the causes of these injuries vary with communities. The final outcome of orbito-ocular morbidities depends on early hospital intervention. The aim of the study therefore was to carry out a demographical analysis of orbito-ocular traumas at the Benue State University Teaching Hospital, Makurdi. This was a retro-prospective study. Folders and radiographic images of eye injury patients in the accident and emergency department of the Benue State University Teaching Hospital (BSUTH) between 2013 and 2015 were assessed. Data was analysed and results presented in tables and pictorial form. It was noted in the study that the mean age±SD of patients was 29.3 17.4 years. Males were mostly affected (80%) and students topped the list (32.5%). Road traffic accident (RTA) was the major cause of orbito-ocular injury (47.5%) and the major orbito-ocular morbidity was blunt or closed ocular injury (37%). We therefore recommended improved surveillance, adequate road safety measures and increased awareness on the need for early ophthalmologic intervention in order to mitigate the incidence.

Copper nanoparticles are embedded into a solvothermally grown thin film of a zirconium metal–organic framework (MOF), NU-1000, by installing single-site Cu(II) into the NU-1000 thin film via solvothermal deposition in MOFs (SIM) followed by electrochemical reduction of Cu(II) to metallic Cu. The obtained Cu nanoparticles are electrochemically addressable and exhibit promising electrocatalytic activity for CO2 reduction in an aqueous electrolyte.

Thermal conductivity is a crucial parameter for managing exothermal gas adsorption in metal organic frameworks (MOFs), but experimental studies have been limited. In this work, the thermal conductivity of a zeolitic imidazolate framework ZIF-8 was experimentally determined on thin films using the 3ω technique at different partial pressures in perfluorohexane, nitrogen, air, and vacuum ambients at 300 K. In contrast to theoretical prediction, the thermal conductivity κ = 0.326 ± 0.002 W/m K was approximately independent of ambient gas species and pressure from atmospheric pressure to vacuum. This work introduces a useful approach for probing MOF thermal conductivity under gas adsorption.

The study was aimed at determining the HIV risk perception and sexual behaviour among commercial motorcyclists in Makurdi, Benue State, Nigeria. The study design was cross sectional study among 344 consenting, registered commercial motorcyclists, aged 18 years and above working in Makurdi, Benue State capital. A multistage sampling technique was used to select the respondents from a total of 5000 motorcyclists spread across 45 stations within Makurdi. Data was collected in September 2014 using structured interviewer administered questionnaire. Analysis was done with SPSS version 20.0. The mean age was 28.18 (± 7.94) years. Approximately 93% of the participants reported ever having sex. The average lifetime number of sexual partners was 8.9 (± 20.26) while 48.0% reported having had more than one sexual partner in the previous one year. A two third of the respondents (66.7%) reported use of condom during their last sex with a non-regular partner. Slightly less than a quarter (24.1%) of the respondents have paid to have sex in the previous one year. However only 29.6% perceived themselves as been at moderate or high risk of contracting HIV. There was significant association between risk perception and use of condom during last sex with any partner {OR-2.687 (95% CI= 1.337 - 5.400) p=0.005}. There is low personal risk perception despite high proportion of risky sexual behaviours among the respondents. HIV prevention interventions among commercial motorcyclists need to be more tailored and with the objective of building assertive skills in addition to imparting knowledge.

A wide range of microbes belonging to all three domains of life is known to generate electrical current and transfer electrons to anodes within a bioelectrochemical system. Typically these exoelectrogens are iron-reducing bacteria (e.g., Geobacter sulfurreducens) that are capable of producing high power density at moderate temperatures. Under nutrient sufficient conditions, other microbes ranging from extremophiles to yeasts can also produce high current densities. On the other hand, electrotrophic microbes grow on electrons derived from the cathode, but such microbes are less diverse and have uncommon traits. Electrotrophs shows low current densities (well below representative exoelectrogens) and utilizes several terminal electron acceptors for cell respiration. Thus, there is a vast diversity of electroactive microbes and their cultivation conditions that opens-up a new avenue for electrochemical devices particularly for H and CH production. The microbial fuel cell has been considered as an eco-friendly technology to harvest electricity harvesting from a variety of carbonaceous substrates. Here, microorganisms can be used as biocatalysts. This chapter provides an introduction to the currently identified electricigens, their taxonomical groups, and electricity-producing abilities. The mechanism of electron transfer from electricigens to electrodes is also discussed.

Introduction: CD4+ T-cell activation is vital for normal wound repair but the factors that control T-cell activation in wounds in vivo are not clear. Our group and others have found increased Th17 activation in diabetic wounds resulting in increased IL-17a and pathologic inflammation that prevents tissue repair. Plasmacytoid dendritic cells (pDC) are antigen presenting cells that are present in early diabetic wound tissue and may play a key role in modulating CD4+ T-cell phenotype. Hence, we hypothesized that diabetic pDCs may influence wound CD4+ T-cells towards Th17 T-cell expansion. Methods: Wild type C57BL/6 mice were fed normal chow diet (13.5% kcal fat; LabDiet) or high fat diet chow (60% kcal fat; Research Diets) for 12–14 weeks to generate the diet-induced obesity (DIO) model of glucose intolerance/insulin resistance. These mice were subsequently wounded, and wound plasmacytoid dendritic cells harvested on day 1 and day 3. These cells were co-cultured with naïve CD4+ T-cells for 3 days, after which T-cell phenotype was determined by flow cytometry. Additionally, pDC in wounds 1-day post wounding were examined by quantitative PCR for cytokine production. Results: Following exposure to DIO pDCs, wild type activated CD4+ T-cells were activated towards a Th17 phenotype via significant increases in TGFb CD4+ T-cell activation and may act to increase inflammation in diabetic wounds.