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Introduction: Healthcare facilities produce a variety of trash that, if handled improperly, could endanger the environment, the health of patients and clients, healthcare personnel, and the general public. Health staff have been given training on infection control and healthcare waste management. It is not apparent whether similar initiatives are taken for sanitary personnel, though. By evaluating sanitary workers’ knowledge, attitudes, and practices about healthcare waste treatment in the Dodoma region of Tanzania, this study sought to clarify the situation. Methods: From March to August 2022 in Dodoma, Tanzania, a descriptive cross-sectional study using a quantitative methodology was conducted on 156 randomly chosen sanitary workers. The primary data collection instruments were structured questionnaires that were conducted by interviewers and a trash checklist that the research team created. Statistical Package for Social Sciences computer software was used to conduct a descriptive analysis of the data with a 95% confidence level and a 5% level of significance. Results: The average age was 28 ± 6.2 years, and there were 74.4% females. Of all of the health institutions under study, 78.4% of the generated medical waste was non-infectious, whereas 21.6% of it was infectious. The share of non-infectious and infectious healthcare waste created by regional referral hospitals was 43.5% and 13.2%, respectively. While 67.8% of sanitary workers believed that handling healthcare waste was not their problem and 63.6% of sanitary workers actually displayed subpar practices of handling healthcare waste, 74.4% of sanitary workers had low understanding about handling healthcare waste. Their procedures for handling medical waste were substantially influenced by the kind of healthcare facility, sex, education, job experience, knowledge, and attitude ( p

Abstract Background There is evidence that an overall healthy diet is associated with lower risk of frailty. However, the effect of diet composition, specifically the role of protein intake on frailty, is mostly unclear. The aim of this study was to evaluate the intake of protein, including total, plant, animal, and dairy protein, in relation to frailty incidence in a large cohort of older women. Methods We analysed data from 85 871 women aged ≥60 participating in the Nurses' Health Study. Intake of protein was measured nine times during follow‐up from 1980 until 2010. Frailty was defined as having at least three of the following five criteria from the Fatigue, Resistance, Ambulation, Illnesses and Loss of Weight (FRAIL) scale: fatigue, low strength, reduced aerobic capacity, having ≥5 illnesses, and weight loss of ≥5%. The occurrence of frailty was assessed every 4 years from 1992 up to 2014. Results During follow‐up, we identified 13 279 incident cases of frailty. Women with a higher intake of plant protein had a lower risk of developing frailty after adjustment for all relevant confounders [relative risks across quintiles of consumption: 1.00, 0.94, 0.89, 0.86, and 0.86; P‐trend

Abstract Background Epidemiological studies have demonstrated a favorable association of whole grain intake with coronary heart disease (CHD) risk, although whether such an inverse association holds true for individual whole grain foods that have various nutritional profiles has not been examined. Methods We followed 74,244 women from Nurses’ Health Study since 1986, 91,430 women from Nurses’ Health Study II since 1991, and 39,455 men from the Health Professionals Follow-Up Study since 1984, who did not have a history of cardiovascular disease or cancer at baseline. Intake of seven individual whole grain foods was repeatedly assessed using a validated semi-quantitative food frequency questionnaire every 2–4 years since baseline. CHD diagnoses were ascertained through review of medical records or death certificates. Results We documented 9461 CHD cases during an average of 25.8 years’ follow-up. In the multivariable-adjusted model, the pooled hazard ratio (HR) (95% CI) of CHD risk corresponding to each one serving/day consumption of total whole grains was 0.93 (0.90–0.95; p trend

Abstract The recently introduced orientation selective deep brain stimulation (OS-DBS) technique freely controls the direction of the electric field’s spatial gradient by using multiple contacts with independent current sources within a multielectrode array. The goal of OS-DBS is to align the electrical field along the axonal track of interest passing through the stimulation site. Here we utilized OS-DBS with a planar 3-channel electrode for stimulating the rat entorhinal cortex (EC) and medial septal nucleus (MSN), two promising areas for DBS treatment of Alzheimer’s disease. The brain responses to OS-DBS were monitored by whole brain functional magnetic resonance imaging (fMRI) at 9.4 T with Multi-Band Sweep Imaging with Fourier Transformation (MB-SWIFT). Varying the in-plane OS-DBS stimulation angle in the EC resulted in activity modulation of multiple downstream brain areas involved in memory and cognition. Contrary to that, no angle dependence of brain activations was observed when stimulating the MSN, consistent with predictions based on the electrode configuration and on the main axonal directions of the targets derived from diffusion MRI tractography and histology. We conclude that tuning the OS-DBS stimulation angle modulates the activation of brain areas relevant to Alzheimer’s disease, thus holding great promise in the DBS treatment of the disease.

Currently, there is a significant shortage of transplantable organs for patients in need. Interspecies chimerism and blastocyst complementation are alternatives for generating transplantable human organs in host animals such as pigs to meet this shortage. While successful interspecies chimerism and organ generation have been observed between evolutionarily close species such as rat and mouse, barriers still exist for more distant species pairs such as human–mouse, marmoset–mouse, human–pig, and others. One of the proposed barriers to chimerism is the difference in developmental stages between the donor cells and the host embryo at the time the cells are introduced into the host embryo. Hence, there is a logical effort to stage-match the donor cells with the host embryos for enhancing interspecies chimerism. In this study, we used an in silico approach to simultaneously stage-match the early developing embryos of four species, including human, marmoset, mouse, and pig based on transcriptome similarities. We used an unsupervised clustering algorithm to simultaneously stage-match all four species as well as Spearman’s correlation analyses to stage-match pairs of donor–host species. From our stage-matching analyses, we found that the four stages that best matched with each other are the human blastocyst (E6/E7), the gastrulating mouse embryo (E6–E6.75), the marmoset late inner cell mass, and the pig late blastocyst. We further demonstrated that human pluripotent stem cells best matched with the mouse post-implantation stages. We also performed ontology analysis of the genes upregulated and commonly expressed between donor–host species pairs at their best matched stages. The stage-matching results predicted by this study will inform in vivo and in vitro interspecies chimerism and blastocyst complementation studies and can be used to match donor cells with host embryos between multiple species pairs to enhance chimerism for organogenesis.

Hunter syndrome is a rare x-linked recessive genetic disorder that affects lysosomal metabolism due to deficiency of iduronate-2-sulfatase (IDS), with subsequent accumulation of glycosaminoglycans heparan and dermatan sulfates (GAG). Enzyme replacement therapy is the only FDA-approved remedy and is an expensive life-time treatment that alleviates some symptoms of the disease without neurocognitive benefit. We previously reported successful treatment in a mouse model of mucopolysaccharidosis type II (MPS II) using adeno-associated viral vector serotype 9 encoding human IDS (AAV9.hIDS) via intracerebroventricular injection. As a less invasive and more straightforward procedure, here we report intravenously administered AAV9.hIDS in a mouse model of MPS II. In animals administered 1.5 × 1012 vg of AAV9.hIDS at 2 months of age, we observed supraphysiological levels of IDS enzyme activity in the circulation (up to 9100-fold higher than wild-type), in the tested peripheral organs (up to 560-fold higher than wild-type), but only 4% to 50% of wild type levels in the CNS. GAG levels were normalized on both sides of the blood-brain-barrier (BBB) in most of tissues tested. Despite low levels of the IDS observed in the CNS, this treatment prevented neurocognitive decline as shown by testing in the Barnes maze and by fear conditioning. This study demonstrates that a single dose of IV-administered AAV9.hIDS may be an effective and non-invasive procedure to treat MPS II that benefits both sides of the BBB, with implications for potential use of IV-administered AAV9 for other neuronopathic lysosomal diseases.

Background Immune-mediated melanoma regression relies on melanoma-reactive T cells infiltrating tumor. Cancer vaccines increase circulating melanoma-reactive T cells, but little is known about vaccine-induced circulating lymphocytes (viCLs) homing to tumor or whether interventions are needed to enhance infiltration. We hypothesized that viCLs infiltrate melanoma metastases, and intratumoral interferon (IFN)-γ or Toll-like receptor 7 (TLR7) agonism enhances infiltration.Methods Patients on two clinical trials (Mel51 (NCT00977145), Mel53 (NCT01264731)) received vaccines containing 12 class I major histocompatibility complex-restricted melanoma peptides (12MP). In Mel51, tumor was injected with IFN-γ on day 22, and biopsied on days 1, 22, and 24. In Mel53, dermal metastases were treated with topical imiquimod, a TLR7 agonist, for 12 weeks, and biopsied on days 1, 22, and 43. For patients with circulating T-cell responses to 12MP by IFN-γ ELISpot assays, DNA was extracted from peripheral blood mononuclear cells (PBMCs) pre-vaccination and at peak T-cell response, and from tumor biopsies, which underwent T-cell receptor sequencing. This enabled identification of clonotypes induced in PBMCs post-vaccination (viCLs) and present in tumor post-vaccination, but not pre-vaccination.Results Six patients with T-cell responses post-vaccination (Mel51 n = 4, Mel53 n = 2) were evaluated for viCLs and vaccine-induced tumor infiltrating lymphocytes (viTILs). All six patients had viCLs, five of whom were evaluable for viTILs in tumor post-vaccination alone. Mel51 patients had viTILs identified in day 22 tumors, post-vaccination and before IFN-γ (median = 2, range = 0–24). This increased in day 24 tumors after IFN-γ (median = 30, range = 4–74). Mel53 patients had viTILs identified in day 22 tumors, post-vaccination plus imiquimod (median = 33, range = 2–64). Three of five evaluable patients across both trials had viTILs with vaccination alone. All five had enhancement of viTILs with tumor-directed therapy. viTILs represented 0.0–2.9% of total T cells after vaccination alone, which increased to 0.6–8.7% after tumor-directed therapy.Conclusion Cancer vaccines induce expansion of new viCLs, which infiltrate melanoma metastases in some patients. Our findings identify opportunities to combine vaccines with tumor-directed therapies to enhance T-cell infiltration and T cell-mediated tumor control. These combinations hold promise in improving the therapeutic efficacy of antigen-specific therapies for solid malignancies.

Introduction Suboptimal feeding practices among caregivers contribute to nutritional-related health problems in children in low and middle-income countries, such as Tanzania. The continuum of the recommended feeding practices has been an utmost challenge among caregivers during the transition from health facilities to homes for improved under-five children’s health. Objective This study assessed feeding practices, dietary diversities, and dietary adequacy among caregivers with under-five children in the Dodoma region, Tanzania. Methods A community-based descriptive cross-sectional study in a quantitative research approach was adopted to study 289 randomly selected caregivers of under-five children in Dodoma region, Tanzania from March to August 2022. The World Health Organization Infant and Young Children Feeding Guidelines was the main data collection tool. Data were analyzed descriptively using a Statistical Package for Social Sciences computer software program version 25. Statistical limits were set at a 95% confidence interval and a 5% significance level. Results Mean age was 26±6.47 of which 68.2% (n = 197) were females. Findings revealed 66.1% of caregivers had unsatisfactory feeding practices. It was observed that 67.8% of the caregivers fed their under-five children inadequately. Only 32.2% of them attained the minimum dietary diversity while 35.3% and 31.5% of caregivers demonstrated feeding practices < and > the recommended minimum Dietary diversity respectively. Moreover, 90.7% of caregivers fed their children group one food while 59.1% of them did not practice feeding the children snacks between meals. Feeding practice, dietary diversity, and dietary adequacy were significantly related to the caregiver’s sex, education level, and socioeconomic status (pConclusion Under-five children are at serious risk of nutritional problems as most caregivers in this study demonstrated unsatisfactory feeding practices on dietary diversities for dietary adequacy below the world health organization recommended Minimum Dietary diversity and Minimum Meal Frequency. Community-based nutritional education programs for caregivers need to be disseminated to the community level to address the problem accordingly.

Abstract Background To compare the prevalence of healthy aging among adults age 70 and older from 5 European countries recruited for the DO-HEALTH clinical trial. Participants were selected for absence of prior major health events. Methods Cross-sectional analysis of DO-HEALTH baseline data. All 2,157 participants (mean age 74.9, SD 4.4; 61.7% women) were included and 2,123 had data for all domains of the healthy aging status (HA) definition. HA was assessed based on the Nurses` Health Study (NHS) definition requiring four domains: no major chronic diseases, no disabilities, no cognitive impairment (Montreal Cognitive Assessment, MoCA ≥25), no mental health limitation (GDS-5

Abstract Arctic warming is affecting snow cover and soil hydrology, with consequences for carbon sequestration in tundra ecosystems. The scarcity of observations in the Arctic has limited our understanding of the impact of covarying environmental drivers on the carbon balance of tundra ecosystems. In this study, we address some of these uncertainties through a novel record of 119 site-years of summer data from eddy covariance towers representing dominant tundra vegetation types located on continuous permafrost in the Arctic. Here we found that earlier snowmelt was associated with more tundra net CO2 sequestration and higher gross primary productivity (GPP) only in June and July, but with lower net carbon sequestration and lower GPP in August. Although higher evapotranspiration (ET) can result in soil drying with the progression of the summer, we did not find significantly lower soil moisture with earlier snowmelt, nor evidence that water stress affected GPP in the late growing season. Our results suggest that the expected increased CO2 sequestration arising from Arctic warming and the associated increase in growing season length may not materialize if tundra ecosystems are not able to continue sequestering CO2 later in the season.

Abstract Background Red meat is a nutrient‐dense source of protein fundamental for older adults; however, red meat is also high in detrimental components, including saturated fat. It is unclear whether habitual red meat consumption is associated with risk of frailty. This study aimed to examine the prospective association between the consumption of total, unprocessed, and processed red meat and the risk of frailty in older adults. Methods We analysed data from 85 871 women aged ≥60 participating in the Nurses' Health Study. Consumption of total, unprocessed, and processed red meat was obtained from repeated food frequency questionnaires administered between 1980 and 2010. Frailty was defined as having at least three of the following five criteria from the FRAIL scale: fatigue, low strength, reduced aerobic capacity, having ≥5 chronic illnesses, and unintentional weight loss ≥5%. The occurrence of frailty was assessed every four years from 1992 to 2014. Results During 22 years of follow‐up (median follow‐up 14 years), we identified 13 279 incident cases of frailty. Women with a higher intake of red meat showed an increased risk of frailty after adjustment for lifestyle factors, medication use, and dietary factors. The relative risk (95% confidence interval) for one serving/day increment in consumption was 1.13 (1.08, 1.18) for total red meat, 1.08 (1.02, 1.15) for unprocessed red meat, and 1.26 (1.15, 1.39) for processed red meat. When each component of the frailty syndrome was individually examined, each of them was positively associated with total red meat consumption, except for the weight loss criterion. Replacing one serving/day of unprocessed red meat with other protein sources was associated with significantly lower risk of frailty; the risk reduction estimates were 22% for fish and 14% for nuts, while for replacement of processed red meat, the percentages were 33% for fish, 26% for nuts, 13% for legumes, and 16% for low‐fat dairy. Conclusions Habitual consumption of unprocessed and processed red meat was associated with a higher risk of frailty. Replacement of red meat by other protein sources might reduce the risk of frailty. These findings are in line with dietary guidelines promoting diets that emphasize plant‐based sources of protein.

Abstract Background Self-directed learning is important in nursing as it is associated with improved clinical and moral competencies in providing quality and cost-effective care among people. However, unethical professional conduct demonstrated by some graduate nurses is linked with the way they are developed in schools alongside the content and pedagogies prescribed in nursing curricula. Pedagogical transformations appear to be inevitable to develop enthusiastic nursing students who can work independently in delivering quality and cost-effective nursing services to people. This study intended to examine the impact of facilitation in a problem-based pedagogy on self-directed learning readiness among undergraduate nursing students in Tanzania. Methods A controlled quasi-experimental design was conducted in Tanzanian higher training institutions from January to April 2019. A 40-item Self-directed learning Readiness scale for nursing education adopted from previous studies measured self-directed learning and the Student A descriptive analysis via a Statistical Package for Social Sciences software program (version 23) was performed to establish nursing students’ socio-demographic characteristics profiles. Independent samples t-test determined mean scores difference of self-directed learning readiness among nursing students between groups while regression analysis was performed to discriminate the effect of an intervention controlled with other co-related factors. Results The post-test results of self-directed learning readiness showed that nursing students scored significantly higher [(M = 33.01 ± 13.17; t (399) = 2.335; 95%CI: 0.486,5.668)] in the intervention group than their counterparts in the control. Findings of SDL readiness subscales were significantly higher among students in the intervention including self-management [(M = 10.11 ± 4.09; t (399) = 1.354; 95%CI: 0.173,4.026)], interest learning [(M = 9.21 ± 2.39; t (399) = 1.189; 95%CI: 0.166,4.323)] and self-control [(M = 13.63 ± 5.05; t (399) = 2.335; 95%CI: 0.486,5.668)]. The probability of nursing students to demonstrate self-directed learning readiness was 1.291 more times higher when exposed to the intervention (AOR = 1.291, p

In the heart, alternative splicing of the igf-I gene produces two isoforms: IGF-IEa and IGF-IEc, (Mechano-growth factor, MGF). The sequence divergence between their E-domain regions suggests differential isoform function. To define the biological actions of MGF’s E-domain, we performed in silico analysis of the unique C-terminal sequence and identified a phosphorylation consensus site residing within a putative 14-3-3 binding motif. To test the functional significance of Ser 18 phosphorylation, phospho-mimetic (S/E18) and phospho-null (S/A18) peptides were delivered to mice at different doses for 2 weeks. Cardiovascular function was measured using echocardiography and a pressure-volume catheter. At the lowest (2.25 mg/kg/day) and highest (9 mg/kg/day) doses, the peptides produced a depression in systolic and diastolic parameters. However, at 4.5 mg/kg/day the peptides produced opposing effects on cardiac function. Fractional shortening analysis also showed a similar trend, but with no significant change in cardiac geometry. Microarray analysis discovered 21 genes (FDR p < 0.01), that were expressed accordant with the opposing effects on contractile function at 4.5 mg/kg/day, with the nuclear receptor subfamily 4 group A member 2 (Nr4a2) identified as a potential target of peptide regulation. Testing the regulation of the Nr4a family, showed the E-domain peptides modulate Nr4a gene expression following membrane depolarization with KCl in vitro. To determine the potential role of 14-3-3 proteins, we examined 14-3-3 isoform expression and distribution. 14-3-3γ localized to the myofilaments in neonatal cardiac myocytes, the cardiac myocytes and myofilament extracts from the adult heart. Thermal shift analysis of recombinant 14-3-3γ protein showed the S/A18 peptide destabilized 14-3-3γ folding. Also, the S/A18 peptide significantly inhibited 14-3-3γ’s ability to interact with myosin binding protein C (MYPC3) and phospholamban (PLN) in heart lysates from dobutamine injected mice. Conversely, the S/E18 peptide showed no effect on 14-3-3γ stability, did not inhibit 14-3-3γ’s interaction with PLN but did inhibit the interaction with MYPC3. Replacing the glutamic acid with a phosphate group on Ser 18 (pSer18), significantly increased 14-3-3γ protein stability. We conclude that the state of Ser 18 phosphorylation within the 14-3-3 binding motif of MGF’s E-domain, modulates protein-protein interactions within the 14-3-3γ interactome, which includes proteins involved in the regulation of contractile function.

Background A vaccine containing 6 melanoma-associated peptides to stimulate helper T cells (6MHP) is safe, immunogenic, and clinically active. A phase I/II trial was designed to evaluate safety and immunogenicity of 6MHP vaccines plus programmed death 1 (PD-1) blockade.Participants and methods Participants with advanced melanoma received 6MHP vaccines in an incomplete Freund’s adjuvant (6 vaccines over 12 weeks). Pembrolizumab was administered intravenously every 3 weeks. Tumor biopsies at baseline and day 22 were analyzed by multiplex immunohistochemistry. Primary end points were safety (Common Terminology Criteria for Adverse Events V.4.03) and immunogenicity (ex vivo interferon-γ ELISpot assay). Additional end points included changes in the tumor microenvironment (TME) and clinical outcomes.Results Twenty-two eligible participants were treated: 6 naïve to PD-1 antibody (Ab) and 16 PD-1 Ab-experienced. Median follow-up was 24.4 months. Most common treatment-related adverse events (any grade) included injection site reactions, fatigue, anemia, lymphopenia, fever, elevated aspartate aminotransferase, pruritus, and rash. Treatment-related dose-limiting toxicities were observed in 3 (14%) participants, which did not cross the study safety bound. A high durable T cell response (Rsp) to 6MHP was detected in only one participant, but twofold T cell Rsps to 6MHP were detected in 7/22 (32%; 90% CI (16% to 52%)) by week 13. Objective clinical responses were observed in 23% (1 complete response, 4 partial responses), including 4/6 PD-1 Ab-naïve (67%) and 1/16 PD-1 Ab-experienced (6%). Overall survival (OS) was longer for PD-1 Ab-naïve than Ab-experienced participants (HR 6.3 (90% CI (2.1 to 28.7)). In landmark analyses at 13 weeks, OS was also longer for those with T cell Rsps (HR 6.5 (90% CI (2.1 to 29.2)) and for those with objective clinical responses. TME evaluation revealed increased densities of CD8+ T cells, CD20+ B cells, and Tbet+ cells by day 22.Conclusions Treatment with the 6MHP vaccine plus pembrolizumab was safe, increased intratumoral lymphocytes, and induced T cell Rsps associated with prolonged OS. The low T cell Rsp rate in PD-1 Ab-experienced participants corroborates prior murine studies that caution against delaying cancer vaccines until after PD-1 blockade. The promising objective response rate and OS in PD-1 Ab-naïve participants support consideration of a larger study in that setting.

A growing need for organs and novel cell-based therapies has provided a niche for approaches like interspecies chimeras. To generate organs from one donor species in another host species requires techniques such as blastocyst complementation and gene editing to successfully create an embryo that has cells from both the donor and the host. However, the task of developing highly efficacious and competent interspecies chimeras is met by many challenges. These interspecies chimeric barriers impede the formation of chimeras, often leading to lower levels of chimeric competency. The barriers that need to be addressed include the evolutionary distance between species, stage-matching, temporal and spatial synchronization of developmental timing, interspecies cell competition and the survival of pluripotent stem cells and embryos, compatibility of ligand–receptor signaling between species, and the ethical concerns of forming such models. By overcoming the interspecies chimera barriers and creating highly competent chimeras, the technology of organ and cellular generation can be honed and refined to develop fully functioning exogenic organs, tissues, and cells for transplantation.

Abstract Background Plant‐based foods have been recommended for health. However, not all plant foods are healthy, and little is known about the association between plant‐based diets and specific molecular subtypes of colorectal cancer (CRC). We examined the associations of healthy and unhealthy plant‐based diets with the incidence of CRC and its molecular subtypes. Methods While 123 773 participants of the Nurses’ Health Study and the Health Professionals Follow‐up Study had been followed up (3 143 158 person‐years), 3077 of them had developed CRC. Healthy and unhealthy plant‐based diet indices (hPDI and uPDI, respectively) were calculated using repeated food frequency questionnaire data. We determined the tumoural status of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and BRAF and KRAS mutations. Results Higher hPDI was associated with lower CRC incidence (multivariable hazard ratio [HR] comparing extreme quartiles, 0.86, 95% confidence interval [CI]: 0.77, 0.96; P‐trend = .04), whereas higher uPDI was associated with higher CRC incidence (multivariable HR comparing extreme quartiles, 1.16, 95% CI: 1.04, 1.29; P‐trend = .005). The association of hPDI significantly differed by KRAS status (P‐heterogeneity = .003) but not by other tumour markers. The hPDI was associated with lower incidence of KRAS‐wildtype CRC (multivariable HR comparing extreme quartiles, 0.74, 95% CI: 0.57, 0.96; P‐trend = .004) but not KRAS‐mutant CRC (P‐trend = .22). Conclusions While unhealthy plant‐based diet enriched with refined grains and sugar is associated with higher CRC incidence, healthy plant‐based diet rich in whole grains, fruits and vegetables is associated with lower incidence of CRC, especially KRAS‐wildtype CRC.

Spatial heterogeneity in methane (CH4) flux requires a reliable upscaling approach to reach accurate regional CH4 budgets in the Arctic tundra. In this study, we combined the CLM-Microbe model with three footprint algorithms to scale up CH4 flux from a plot level to eddy covariance (EC) tower domains (200 m × 200 m) in the Alaska North Slope, for three sites in Utqiaġvik (US-Beo, US-Bes, and US-Brw), one in Atqasuk (US-Atq) and one in Ivotuk (US-Ivo), for a period of 2013–2015. Three footprint algorithms were the homogenous footprint (HF) that assumes even contribution of all grid cells, the gradient footprint (GF) that assumes gradually declining contribution from center grid cells to edges, and the dynamic footprint (DF) that considers the impacts of wind and heterogeneity of land surface. Simulated annual CH4 flux was highly consistent with the EC measurements at US-Beo and US-Bes. In contrast, flux was overestimated at US-Brw, US-Atq, and US-Ivo due to the higher simulated CH4 flux in early growing seasons. The simulated monthly CH4 flux was consistent with EC measurements but with different accuracies among footprint algorithms. At US-Bes in September 2013, RMSE and NNSE were 0.002 μmol m−2 s−1 and 0.782 using the DF algorithm, but 0.007 μmol m−2 s−1 and 0.758 using HF and 0.007 μmol m−2 s−1 and 0.765 using GF, respectively. DF algorithm performed better than the HF and GF algorithms in capturing the temporal variation in daily CH4 flux each month, while the model accuracy was similar among the three algorithms due to flat landscapes. Temporal variations in CH4 flux during 2013–2015 were predominately explained by air temperature (67–74%), followed by precipitation (22–36%). Spatial heterogeneities in vegetation fraction and elevation dominated the spatial variations in CH4 flux for all five tower domains despite relatively weak differences in simulated CH4 flux among three footprint algorithms. The CLM-Microbe model can simulate CH4 flux at both plot and landscape scales at a high temporal resolution, which should be applied to other landscapes. Integrating land surface models with an appropriate algorithm provides a powerful tool for upscaling CH4 flux in terrestrial ecosystems.

Wetland methane emissions contribute to global warming, and are oversimplified in climate models. Here the authors use eddy covariance measurements from 48 global sites to demonstrate seasonal hysteresis in methane-temperature relationships and suggest the importance of microbial processes.

Summary: Background: The obesity epidemic in the USA continues to grow nationwide. Although excess weight-related mortality has been studied in general, less is known about how it varies by demographic subgroup within the USA. In this study we estimated excess mortality associated with elevated body weight nationally and by state and subgroup. Methods: We developed a nationally-representative microsimulation (individual-level) model of US adults between 1999 and 2016, based on risk factor data from 6,002,012 Behavioral Risk Factor Surveillance System respondents. Prior probability distributions for hazard ratios relating body-mass index (BMI) to mortality were informed by a global pooling dataset. Individual-level mortality risks were modelled accounting for demographics, smoking history, and BMI adjusted for self-report bias. We calibrated the model to empirical all-cause mortality rates from CDC WONDER by state and subgroup, and assessed the predictive accuracy of the model using a random sample of data withheld from model fitting. We simulated counterfactual scenarios to estimate excess mortality attributable to different levels of excess weight and smoking history. Findings: We estimated that excess weight was responsible for more than 1300 excess deaths per day (nearly 500,000 per year) and a loss in life expectancy of nearly 2·4 years in 2016, contributing to higher excess mortality than smoking. Relative excess mortality rates were nearly twice as high for women compared to men in 2016 (21·9% vs 13·9%), and were higher for Black non-Hispanic adults. By state, overall excess weight-related life expectancy loss ranged from 1·75 years (95% UI 1·57–1·94) in Colorado to 3·18 years (95% UI 2·86-3·51) in Mississippi. Interpretation: Excess weight has substantial impacts on mortality in the USA, with large disparities by state and subgroup. Premature mortality will likely increase as obesity continues to rise. Funding: The JPB Foundation, NIH, CDC

Objective: The aim of this study was to test the individual and combined benefit of vitamin D, omega-3, and a simple home strength exercise program on the risk of any invasive cancer.Design: The DO-HEALTH trial is a three-year, multicenter, 2 × 2 × 2 factorial design double-blind, randomized-controlled trial to test the individual and combined benefit of three public health interventions.Setting: The trial was conducted between December 2012 and December 2017 in five European countries.Participants: Generally healthy community-dwelling adults ≥70 years were recruited.Interventions: Supplemental 2000 IU/day of vitamin D3, and/or 1 g/day of marine omega-3s, and/or a simple home strength exercise (SHEP) programme compared to placebo and control exercise.Main outcome: In this pre-defined exploratory analysis, time-to-development of any verified invasive cancer was the primary outcome in an adjusted, intent-to-treat analysis.Results: In total, 2,157 participants (mean age 74.9 years; 61.7% women; 40.7% with 25-OH vitamin D below 20 /ml, 83% at least moderately physically active) were randomized. Over a median follow-up of 2.99 years, 81 invasive cancer cases were diagnosed and verified. For the three individual treatments, the adjusted hazard ratios (HRs, 95% CI, cases intervention versus control) were 0.76 (0.49–1.18; 36 vs. 45) for vitamin D3, 0.70 (0.44–1.09, 32 vs. 49) for omega-3s, and 0.74 (0.48–1.15, 35 vs. 46) for SHEP. For combinations of two treatments, adjusted HRs were 0.53 (0.28–1.00; 15 vs. 28 cases) for omega-3s plus vitamin D3; 0.56 (0.30–1.04; 11 vs. 21) for vitamin D3 plus SHEP; and 0.52 (0.28–0.97; 12 vs. 26 cases) for omega-3s plus SHEP. For all three treatments combined, the adjusted HR was 0.39 (0.18–0.85; 4 vs. 12 cases).Conclusion: Supplementation with daily high-dose vitamin D3 plus omega-3s, combined with SHEP, showed cumulative reduction in the cancer risk in generally healthy and active and largely vitamin D–replete adults ≥70 years.Clinical Trial Registration:ClinicalTrials.gov, Identifier: NCT01745263.

Background Both genetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes. Methods and findings We analyzed data from 35,759 men and women in the United States participating in the Nurses’ Health Study (NHS) I (1986 to 2016) and II (1991 to 2017) and the Health Professionals Follow-up Study (HPFS; 1986 to 2016) with available genetic data and who did not have diabetes, cardiovascular disease, or cancer at baseline. Genetic risk was characterized using both a global polygenic score capturing overall genetic risk and pathway-specific polygenic scores denoting distinct pathophysiological mechanisms. Diet quality was assessed using the Alternate Healthy Eating Index (AHEI). Cox models were used to calculate hazard ratios (HRs) for type 2 diabetes after adjusting for potential confounders. With over 902,386 person-years of follow-up, 4,433 participants were diagnosed with type 2 diabetes. The relative risk of type 2 diabetes was 1.29 (95% confidence interval [CI] 1.25, 1.32; P < 0.001) per standard deviation (SD) increase in global polygenic score and 1.13 (1.09, 1.17; P < 0.001) per 10-unit decrease in AHEI. Irrespective of genetic risk, low diet quality, as compared to high diet quality, was associated with approximately 30% increased risk of type 2 diabetes (Pinteraction = 0.69). The joint association of low diet quality and increased genetic risk was similar to the sum of the risk associated with each factor alone (Pinteraction = 0.30). Limitations of this study include the self-report of diet information and possible bias resulting from inclusion of highly educated participants with available genetic data. Conclusions These data provide evidence for the independent associations of genetic risk and diet quality with incident type 2 diabetes and suggest that a healthy diet is associated with lower diabetes risk across all levels of genetic risk. In an observational study of 3 cohorts in the United States, Jordi Merino, Marta Guasch-Ferré, Jun Li, and colleagues investigate the individual and combined associations between genetic risk, diet quality, and risk of type 2 diabetes. Author summary Why was this study done? Both genetic and lifestyle factors contribute to individual-level risk of type 2 diabetes. While previous studies have shown that adherence to a healthy lifestyle is associated with reduced risk of type 2 diabetes regardless of genetic risk, the partial characterization of genetic risk and the predominant assessment of interactions on the multiplicative scale might have prevented previous studies from identifying genetic profiles interacting with dietary exposures. Therefore, understanding how genetic risk and diet quality contribute to the development of type 2 diabetes is important to support evidence-based preventive interventions. What did the researchers do and find? In 3 cohort studies involving 35,759 men and women in the US, we used novel polygenic scores for type 2 diabetes to systematically evaluate the presence of additive and multiplicative interactions between genetic risk and diet quality on the development of type 2 diabetes. We found that both low diet quality and increased overall or pathway-specific genetic risk were independently associated with higher risk of type 2 diabetes. We documented that within any genetic risk category, high diet quality, as compared to low diet quality, was associated with a nearly 30% lower risk of type 2 diabetes. Further, we showed that the risk of type 2 diabetes attributed to the combination of increased genetic risk and low diet quality was similar to the sum of the risks associated with each factor alone. What do these findings mean? Results from this study suggest that consuming a healthier diet is associated with a lower risk of type 2 diabetes regardless of genetic risk. Our results underscore the value of genetic risk assessment to identify individuals at increased disease risk and their potential for risk stratification and surveillance. Such knowledge can serve to inform and design future strategies to advance the prevention of type 2 diabetes.

Abstract We examined whether regular television (TV) viewing at ages 3–5 and 5–10 years is related to the incidence of type 2 diabetes mellitus (T2D) in adult women. We used data from 34,512 mother-nurse daughter dyads in the Nurses’ Health Study (NHS) II and the Nurses’ Mothers’ Cohort Study. Mothers of NHS II participants completed a questionnaire on their pregnancy with the nurse and her early life experience. During 391,442 person-years of follow-up from 2001 to 2013, 1515 nurses developed T2D. Increasing levels of TV viewing at 3–5 years of age retrospectively reported by the mothers were related to a greater risk of T2D in adulthood: multivariable-adjusted hazard ratios (HRs) for ≤ 1, 2, and ≥ 3 h/day vs. no TV viewing were 1.11 [95% confidence interval (CI) 0.96–1.28], 1.20 (95% CI 1.02–1.41), and 1.35 (95% CI 1.11–1.65), p trend = 0.002, respectively, after adjustment for early life variables, including childhood physical activity and adiposity. Retrospectively reported TV viewing for ≥ 3 h/day at 5–10 years of age was associated with a 34% greater risk of adult T2D (HR 1.34, 95% CI 1.05–1.70, p trend

Abstract This research is the first to produce induced pluripotent stem cell-derived inner ear sensory neurons in the Neurog1 +/− heterozygote mouse using blastocyst complementation. Additionally, this approach corrected non-sensory deficits associated with Neurog1 heterozygosity, indicating that complementation is specific to endogenous Neurog1 function. This work validates the use of blastocyst complementation as a tool to create novel insight into the function of developmental genes and highlights blastocyst complementation as a potential platform for generating chimeric inner ear cell types that can be transplanted into damaged inner ears to improve hearing.

Abstract Background Academic motivation is most important as a key determinant of competent and motivated nurses who are often considered as frontline healthcare providers who devote most of their time taking care of clients and patients. However, most of them demonstrate remarkable differences in their academic performances during their schooling that might be due to the differences in their academic motivation and achievement motivation. There appears a growing concern to rethink the approaches on how nurses are prepared, explore, and test novel approaches for delivering the nursing curricula. This study tested the effect of Problem Based Facilitatory Teaching pedagogy on academic motivation among nursing students in Tanzania, higher learning institutions. Methods A pre-post-test controlled quasi-experimental study of 401 purposively selected participants was conducted between February and June 2018. The study was not a clinical randomized controlled trial and thus it has not been identified in the title and no summary of trial design, its methods, results, and conclusion. The Auditing Inventory developed by the researcher measured the intervention and a Questionnaire titled “Academic Motivation Scale,” was adopted to measure academic motivation. Statistical Product for Service Solutions software program version 23 was used to perform descriptive analysis to establish participants’ sociodemographic profiles. Regression analysis was performed to determine the association between variables. Results Findings revealed that 65.8% of participants were males. Post-test findings showed 70.3% of participants demonstrated the motive to learn contrary to 34.9% at baseline. The odds of an intervention to influence academic motivation among participants was higher than the control (AOR = 1.720; p 0.05, 95%CI: 0.405, 1.129) and Amotivation to learn (AOR = 0.538, p > 0.05; 95%CI: 0.283, 1.022) compared to the control. Conclusion The Problem Based Facilitatory Teaching pedagogy was a predictive factor to intrinsic academic motivation among nursing students. The approach demonstrated educational potentials to change the spectrum of nursing competency and quality of care to patients or clients. This study suggests problem-based facilitatory teaching pedagogy be integrated into the nursing curriculum in Tanzania as it is feasible.

The intensive use of lead (Pb)-based insecticides (lead arsenate, PbHAsO4) has led to Pb accumulation in agricultural soil, endangering human health through the possibility of transferring it to the food chain. The aim of this study was to evaluate the potential for the immobilization of Pb in the soil by applying organic (sludge, biocompost, yard compost, and peat) and inorganic (bonemeal, zeolite, lime, and wood ash) amendments, in combination with diammonium phosphate (DAP) in a greenhouse experiment. Two amendment rates were used: low and high, and three rates of DAP: 0 (zero), low (0.25 g of DAP/kg soil), and high (1.25 g DAP/kg soil). The results showed that the dry yield of carrot (Daucus carota susp. sativus) was the highest for the organic amendments in combination with the low rate of DAP. The high rate of inorganic amendments also increased the yield. Applications of inorganic bonemeal, inorganic lime, and inorganic wood ash yielded the lowest Pb tissue concentration (TC), and organic peat had the highest Pb TC. Inorganic bonemeal combined with DAP most effectively immobilized Pb in soil.

Background: Despite the potential protective effect of a plant-based diet against chronic obstructive pulmonary disease (COPD), it remains unknown whether intake of different types of plant foods is beneficial for COPD. Our aims were to determine whether adherence to the healthful version of a plant-based diet (healthful Plant-based Diet Index (hPDI)) is associated with a lower COPD risk, whereas adherence to the unhealthful version (unhealthful Plant-based Diet Index (uPDI)) is associated with a higher COPD risk. Methods: 46,948 men from the Health Professionals Follow-up Study, 73,592 women from the Nurses’ Health Study, and 85,515 women from the Nurses’ Health Study II who completed biennial questionnaires from 1984–2018. We derived diet scores from repeated validated food frequency questionnaires. Among 5,661,994 person-years of follow-up, we documented 2605 validated COPD cases between 1984–2018. Results: After tight control for smoking and other potential confounders, COPD risk was 46% lower among participants with the highest hPDI score compared to those with the lowest score. Conversely, COPD risk was 39% higher among participants with the highest uPDI. Further adjustment for processed meat intake led to similar results. Conclusions: These findings provide further evidence for consuming a diet that emphasizes healthful plant foods to optimize lung health.

Terrestrial vegetation communities are experiencing rapid and novel changes to photosynthetic rates under the changing climate. Chaparral, a semi-arid shrubland ecosystem of the Southwestern United States and Northern Mexico, is projected to experience substantial increases in aridity and stochastic precipitation. This study identifies the primary meteorological drivers of photosynthesis for three widespread chaparral shrub species— Adenostoma sparsifolium, Adenostoma fasciculatum, and Ceanothus perplexans —from 2019 to 2021. Monthly leaf-level carbon exchange rates, water potentials (WPs), and meteorological conditions were collected for each species. Average monthly primary productivity ( n = 25) demonstrated vapor pressure deficit (VPD) as a significant limit to photosynthetic rates for A. sparsifolium and A. fasciculatum . VPD was also the most influential predictor of WP for all three species. These results suggest increasing atmospheric dryness as a key predictor for reduction in chaparral primary productivity, particularly for deeply-rooted, resprouting species. There are additional indications that VPD could exacerbate drought-related mortality for C. perplexans and A. sparsifolium by pushing WP to novel extremes. This study concludes that atmospheric dryness, across 3 years of differing soil water stress levels, was consistently a substantial physiological limitation for three common, chaparral species. Although this experiment occurred over a limited window and cannot assess climatic response trends, acute increases in air temperature and VPD within the region would exacerbate photosynthetic limitation for these species and may contribute to declining primary productivity in broader chaparral ecosystems.

Abstract Adolescent drinking is associated with higher risks of proliferative benign breast disease (BBD) and invasive breast cancer (BC). Furthermore, adolescent nut and fiber consumptions are associated with lower risks of benign lesions and premenopausal BC. We hypothesize that diet (nuts, fiber) may mitigate the elevated BBD risk associated with alcohol. A prospective cohort of 9031 females, 9–15 years at baseline, completed questionnaires in 1996–2001, 2003, 2005, 2007, 2010, 2013, and 2014. Participants completed food frequency questionnaires in 1996–2001. In 2005, participants (>=18 years) began reporting biopsy-confirmed BBD (N = 173 cases). Multivariable logistic regression estimated associations between BBD and cross-classified intakes (14–17 years) of alcohol and peanut butter/nuts (separately, total dietary fiber). Only 19% of participants drank in high school; drinking was associated with elevated BBD risk (OR = 1.75, 95% CI: 1.20–2.56; p = 0.004) compared to nondrinkers. Participants consuming any nuts/butter had lower BBD risk (OR = 0.64, 95% CI: 0.45–0.90; p = 0.01) compared to those consuming none. Participants in top 75% fiber intake had lower risk (OR = 0.57, 95% CI: 0.40–0.81; p = 0.002) compared to bottom quartile. Testing our hypothesis that consuming nuts/butter mitigates the elevated alcohol risk, analyzing alcohol and nuts combined found that those who consumed both had lower risk (RR = 0.47, 95% CI: 0.24–0.89; p = 0.02) compared to drinkers eating no nuts. Our analysis of alcohol and fiber together did not demonstrate risk mitigation by fiber. For high school females who drink, their BBD risk may be attenuated by consuming nuts. Due to modest numbers, future studies need to replicate our findings in adolescent/adult females. However, high school students may be encouraged to eat nuts and fiber, and to avoid alcohol, to reduce risk of BBD and for general health benefits.

Environmental and dietary factors are known to play a role in the development of coronary heart disease. Here the authors apply a genomic-inspired methodology to Nurses’ Health Study data to explore comprehensively and agnostically the association of 257 nutrients and 117 foods with coronary heart disease risk.

Abstract An abnormal clinical Allen's test is not a definitive exclusion criterion for free radial forearm flap use. A surgical Allen's test may be useful to determine whether flap harvest is feasible in patients with an abnormal clinical Allen's test.

Background: Intake of conventionally grown fruits and vegetables (FVs) is an important route of exposure to pesticide residues in the general population. However, whether health risk stemming from exposure to pesticides through diet could offset benefits of consuming FVs is unclear. Objective: We assessed the association of FV intake, classified according to their pesticide residue status, with total and cause-specific mortality. Methods: We followed 137,378 women (NHS, 1998–2019, and NHSII, 1999–2019) and 23,502 men (HPFS, 1998–2020) without cardiovascular disease, cancer, or diabetes at baseline. FV intake was assessed using validated food frequency questionnaires and categorized as having high- or low-pesticide-residues using data from the USDA Pesticide Data Program. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for total and cause-specific mortality associated with high- and low-pesticide-residue FV intake. Results: A total of 27,026 deaths, including 4,318 from CVD and 6,426 from cancer, were documented during 3,081,360 person-years of follow-up. In multivariable-adjusted analyses, participants who consumed ≥4 servings/day of low-pesticide-residue FVs had 36% (95% CI: 32%-41%) lower mortality risk compared to participants who consumed

Purpose/ObjectivesClinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes.Materials and MethodsPatients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated.ResultsTwenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated.ConclusionsIn our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.

Category: Midfoot/Forefoot Introduction/Purpose: The etiology of hallux rigidus (HR) is not well understood and Its association with first-ray hypermobility, hallux valgus and metatarsus primus elevatus (MPE) has not been clearly proven. MPE, elevated first metatarsal has been a topic of debate since Lambrinudi`s first description. Recent studies have supported MPE in hallux rigidus by measuring with various methods on wightbearing lateral radiographs, but there are limitations of conventional radiography due to variation in X- ray projection and superimposed metatarsals regardless of the methods of measurement. Our objective was to assess MPE and other associated parameters with hallux rigidus via radiography and WBCT for convergent validity and to evaluate the use of classification system used in conventional radiography with WBCT. Methods: This is a single-center, retrospective study from prospectively collected data. 20 symptomatic hallux rigidus patient with weightbearing radiograph and WBCT were enrolled from October 2014 to December 2020. Measured parameters included hallux valgus angle (HVA), intermetatarsal angle (IMA), hallux interphalangeal angle (HIPA), distal metatarsal articular angle (DMAA), 1st TMT joint version, First and second metatarsal lengths, Metatarsus adductus angle, 2nd cuneiform-2nd metatarsal angle, Talus-1st Metatarsal Angel, First and second metatarsal declination angles, and MPE. MPE was measured as the direct distance between 1st and 2nd metatarsals (modified Horton index). All patients were graded according to the radiographic criteria of Coughlin and Shurnas classification on radiographs and WBCT, separately. Paired T-test was performed to compare radiographic measurements with WBCT. Results: Mean age was 55.9, 12 males and 8 females. HVA (15.73 in X-ray vs 14.04 in WBCT), AP first TMT version (16.25 vs 16.47), 2nd cuneiform-2nd metatarsal angle (24.54 vs 26.60), Talus-1st Metatarsal Angel (-7.67 vs -7.89) were not different between radiograph and WBCT. MPE was measured higher in WBCT by 0.86 mm compared to radiograph. First metatarsal declination angle was lower in WBCT by 2.9° indicating increased MPE. When graded with radiographic findings, 5 (25%) patients were grade 1, 5 (25%) patients were grade 2 and 10 (50%) grade 3, when graded with WBCT, 1 (5%) patient had grade 1, 3 (15%) patients were grade 2 and 16 (80%) grade 3. Dorsal subluxation/translation of first metatarsal at first TMT joint was observed 3 (15%) in radiograph and 9 (45%) in WBCT. Conclusion: HVA, AP first TMT version, 2nd cuneiform-2nd metatarsal angle, Talus-1st Metatarsal Angel demonstrated consistent measurements in radiograph and WBCT. MPE was measured higher in WBCT when measured with direct distance (0.86 mm) between the first and second metatarsals using modified Horton index and first metatarsal declination angle (2.9°). When graded with WBCT, the subchondral cyst in the proximal phalanx and metatarsal head were better delineated leading to higher grade in WBCT. Further studies are needed for inter-rater reliability and discriminant validity of the measurements determined by differences between different groups (HR vs control).

Category: Midfoot/Forefoot Introduction/Purpose: The etiology of hallux rigidus has been unknown. Metatarsus primus elevates (MPE), elevated first metatarsal has been controversial. Recent studies have supported significantly elevated first metatarsal in hallux rigidus patients. Bouaicha reported MPE greater than 5 mm could be a predictive factor of hallux rigidus. Lateral weightbearing radiographs has been used to evaluate MPE, However, there are limitations of conventional radiography including variation in X-ray projection angle and foot position and superimposition of metatarsals. Cheung assessed foot alignment utilizing 3D reconstructions from WBCT and concluded that hallux rigidus patients had increased MPE. Our objective was to assess MPE and anatomical characteristics in foot alignment of hallux rigidus patients compared to a control group using WBCT. This is the first study measuring MPE on WBCT. Methods: This is a single-center, retrospective study from prospectively collected data. 20 patients with hallux rigidus and WBCT data were enrolled from October 2014 to December 2020. As a control group, 20 patients with various foot and ankle pathologies were selected. Measured WBCT parameters included 1st TMT joint version, HVA, IMA, DMAA, 1st and 2nd metatarsal lengths, Foot width, Sesamoid station and rotation angle, 1st-5th Metatarsal Angle, Metatarsus adductus angle, 2nd cuneiform-2nd metatarsal angle, Talus-1st Metatarsal Angel, 1st Metatarsal-Proximal Phalanx Angle, 1st and 2nd metatarsal declination angles and ratio, and MPE. MPE was measured as a direct distance between 1st and 2nd metatarsals using a line tangential to the first metatarsal and another perpendicular line at the metadiaphyseal junction to reach second metatarsal on parasagittal view. A Cut-off value of MPE was calculated using receiver operating characteristic curve. Two investigators independently assessed each WBCT. Results: Mean age was 43.3 in control group (45% male, 55% female) and 55.9 in HR group (60% male, 40% female). Significant differences were found in several facets of foot anatomy between HR and control groups including HVA (7.57 in control vs 14.05 in HR), DMAA (3.89 vs 8.06), forefoot width (92.96 vs 95.47), 1st MT declination angle (20.17 vs 17.82), 1st/2nd MT declination ratio (83.52 vs 76.02), and MPE (3.24 mm vs 5.40 mm). MPE was significantly higher in hallux rigidus group in all three parasagittal views (unmodified, parallel to 1st metatarsal and 2nd metatarsal). Dorsal subluxation/translation of the first metatarsal was observed at 1st TMT joint in the parasagittal view of WBCT in 9 (45%) patients of hallux rigidus group suggesting sagittal instability. No patient in control group had dorsal subluxation/translation. A cut-off value of MPE was 4.56 mm with 80% sensitivity and 90% specificity. Conclusion: To evaluate MPE on WBCT, we used a new direct measurement on parasagittal views. We found a significant difference in MPE in HR. Our WBCT results are consistent with other studies using conventional radiographs. A cut-off value of WBCT MPE for diagnosis of HR was 4.56 mm in our cohort. Considering 45% patients of the HR group had dorsal subluxation/translation of first metatarsal at 1st TMT and increased HVA, Hallux rigidus may be associated with first ray instability predominantly in sagittal plane with resultant MPE with varying degree of combined coronal plane instability resulting in increased HVA.

Category: Other; Ankle; Arthroscopy; Bunion; Hindfoot; Lesser Toes; Midfoot/Forefoot; Trauma Introduction/Purpose: The COVID-19 pandemic has brought a major increase in telemedicine utilization to conserve resources and maintain social distancing. The rapid transition over a short period of time has exposed challenges and limitations of virtual visits, especially with regards to performing an effective and efficient physical examination. Within months, orthopedic telemedicine guides were published for patient education and facilitating the musculoskeletal examination. These publications, however, included only a short video clip to explain to the patient how to participate in the examination during a telemedicine visit. In the foot and ankle subspecialty, the closely adjacent complex anatomy compared to other areas of the body presents unique challenges for physical exam. Methods: To optimize the efficiency and efficacy of the examination portion of the visit for both patients and providers, we designed and recorded an instructional video that is sent to all patients by email a minimum of 1 week prior to their appointment. This video consists of a step-by-step guide on how to take suitable photos and videos of their feet and ankles for the physical examination portion of their visit. These media files are then directly uploaded by the patients into their EMR or emailed to the physician's office to be uploaded for access by the provider before and during the virtual visit. Along with the video, patients are given a link to test their microphone and camera in advance of the visit to ensure adequate functionality and positioning. Results: Our pre-appointment instructional video has been effective to methodically replicate the most important aspects of an in-person foot and ankle evaluation. Both physicians and patients appear to benefit from the tutorial video by having more time during the telemedicine visit to focus on history, assessment, and plan. Patients are more actively involved in the clinical data collection process because they are educated on what to expect and how to best prepare and participate in telemedicine visits. Moreover, having a set of systematic and detailed photos and recordings of the patient's foot and ankle beforehand better focuses interaction and discussion with the patient during the telemedicine encounter. Additionally, these are saved into the patient's electronic medical record, available for reference and later review. Conclusion: Physical examination plays a critical role in diagnosis and treatment in the orthopedic foot and ankle subspecialty. More research is needed to discern how best to utilize virtual modalities as they become more commonplace, not just from the imposition from the COVID pandemic but also from the standpoint of patient convenience and time efficiency. Here we have described our creation of a pre-visit educational video to guide and engage patients on acquiring invaluable physical examination information for the orthopedic foot and ankle telemedicine encounter.

Category: Trauma; Midfoot/Forefoot Introduction/Purpose: Fractures of the proximal fifth metatarsal are common injuries with a unique history. Treatment of these fractures is controversial, in part due to confusion regarding the nomenclature of the fracture subtypes. The most commonly utilized classification system is the Lawrence and Botte classification, which separates fractures into zones 1, 2, and 3 based on their relationship to the tuberosity and the 4th-5th intermetatarsal articulation. The purpose of this study was to evaluate the inter-rater and intra-rater reliability of the Lawrence and Botte classification of fifth metatarsal base fractures. Methods: Thirty sets of x-rays representing an equal number of zone 1, zone 2 and zone 3 fractures of varying chronicity were sent to eleven fellowship trained orthopedic foot and ankle surgeons. Surgeons were asked to classify each fracture according to the Lawrence and Botte classification system (round 1). No review of the classification system or visual aids were provided. Two weeks later, the same set of x-rays were reordered and renumbered in a random fashion. The surgeons then re-classified each fracture in a blinded fashion under the same conditions (round 2). Inter-rater and intra-rater reliability was summarized using the kappa statistic. To determine the source of variability between the zones, additional analyses were performed to determine the kappa statistic for a) combined zone 1 and 2 fractures versus zone 3 fractures and b) combined zone 2 and 3 fractures versus zone 1 fractures. Results: The Lawrence and Botte classification demonstrated substantial overall inter-rater agreement for both rounds 1 and 2 (kappa = 0.66 and 0.65, respectively). Zone 1 fractures demonstrated the highest inter-rater reliability (kappa = 0.83 and 0.83). There was moderate agreement for zone 2 fractures (kappa = 0.51 and 0.50). There was substantial agreement for zone 3 fractures (kappa = 0.64 and 0.65). Dichotomous evaluation of the zone 1 vs. combined zones 2-3 boundary yielded excellent agreement (kappa = 0.83, 0.83). The combined zones 1-2 vs. zone 3 boundary yielded a much lower agreement (kappa = 0.66, 0.65). Intra-rater reliability varied by individual, with kappa values ranging from 0.60 to 0.90, corresponding to modest to almost perfect agreement. Conclusion: The Lawrence and Botte classification system has overall substantial inter-rater and intra-rater reliability, but assessment of the interface between zone 2 and zone 3 fractures is much less reliable than that between zone 1 and zone 2. Previous studies of isolated zone 1 fractures most likely contain a homogenous fracture cohort, while studies of zone 2 or zone 3 fractures are likely to include a mixture of fracture types. Future studies may utilize supplemental imaging or modify the classification to best determine treatment of these more distal fractures.

Background Adolescents are currently becoming sexually active before their 18th birthday during which they have to battle with unsafe sexual behaviours, teenage pregnancies, sexually transmitted infections (STIs), and school dropouts. The trend is linked with low soft skills (self-esteem and assertiveness skills) for them to make informed, reasoned, and responsible decisions over sexual activities. This study designed and tested the effect of integrated reproductive health (RH) lesson materials in a problem-based pedagogy (PBP) to enhance soft skills for safe sexual behaviour among adolescents in Tanzania. Methods A double-blinded clustered randomized controlled trial was conducted between September 2019 and September 2020 among 660 randomly selected adolescents. A Sexual-risk Behaviour Beliefs and Self-esteem Scale adopted from previous studies measured soft skills for safe sexual behaviour. A descriptive statistical analysis was performed by using the statistical analysis software programme version 9.4. The effect of the intervention was determined using Linear Mixed Model set at α error probability = 5% significance level (95% confidence interval) and a β error probability = 0.80. Findings Adolescents’ mean age was 15±1.869 with 57.5% females. The end-line findings indicated that the coefficient of soft skills was significantly higher among adolescents in the hybrid PBP (β=9.0986, pConclusion The intervention substantially enhanced soft skills for safe sexual behaviour among adolescents of both sex. Despite the fact that scores for soft skills varied across the study timelines, adolescents demonstrated significant intentions to abstain from sexual intercourse, delay sexual relationships, negotiate condom use, and withstand sexual coercions. The PBP may need to be incorporated in ordinary level secondary school curricula as a formal guide to teachers and or health workers to optimally prepare adolescents for their healthy adulthood.

Abstract Aim Currently, there has been a progressive shortage of not only the number of frontline healthcare providers but also a decline in the quality of nursing care. There is a growing concern to rethink the approaches on how nurses are prepared, explore and test novel approaches for delivering the nursing curricula. This study tested the effect of the problem‐based facilitatory teaching approach on metacognition among nursing students in Tanzania, higher learning institutions. Design A controlled pre‐/post‐test quasi‐experimental study design with a quantitative research approach was employed in this study. Methods The study was conducted between February–June 2019 including two purposively selected higher learning institutions in the Dodoma region, the central zone of Tanzania. The 401 randomly selected undergraduate nursing students (interventional = 134 and control = 267) were involved. The auditing inventory developed by the researcher measured the intervention, and the questionnaire titled Metacognition Strategies in Nursing was adopted to measure the metacognition, respectively. Statistical analysis was performed using the Statistical Package for the Social Solution (SPSS) software program version 23. Results Findings indicated that 65.8% of the study participants were males. The post‐test findings revealed a significant gain in metacognition scores among participants in an intervention group between (M = 23.27; SD = 1.716) at baseline and (M = 66.31; SD = 6.204) post‐intervention. 63.4% of the total sample in an intervention group demonstrated a high level of knowledge about the regulation of cognition compared to their counterpart control group. However, 69.1% (N = 85) participants in the control group performed better for the knowledge about cognition. With the control of other factors, the intervention was found to be more times likely to influence metacognition among nurse students (AOR = 1.603, p

Abstract Background Solid waste management is both an urban and rural problem because every person is considered a producer of wastes. It has been noted to be a global universal issue, which affects every individual, families, communities and governments and thus, needs to be addressed through sustainable strategies. This study aimed at characterizing solid wastes; assessing the levels of awareness of vendors on the sustainable solid waste management measures; and identifying techniques used to handle solid waste generated at the Majengo market in Dodoma City, Tanzania. Methods The study adopted an exploratory descriptive case study, with a mixed research approaches with a minimum sample of 196 conviniently selected respondents. Semi-structured questionnaires developed by the researcher were the main data collection tools to characterize solid wastes, measure levels of awareness about sustainable solid waste management approaches (SWM) and identify solid waste handling techniques among vendors at the market. Quantitative and Qualitative data were analyzed by using the Statistical Product for Social Sciences version 23 and thematic analysis respectively. Results Findings showed that 55% of vendors were males. Majority of the sampled vendors (56%) were not aware of SWM. On the other hand, crops/food and animal product remains were reported to be the most generated solid wastes (94.4%) with the rate of > 2 tons/day equivalent to 72.4% of the overall solid waste generation at the market. SWM services were reported to be provided by City council (85.7%) with the main equipment/tool used to store solid wastes (SW) being containers without lids (88.3%). The dumpsite was the main site for SW disposal (80.1%). Nevertheless, 92.9% of the sampled vendors reported that SWM strategies were there at the market though not adhered to accordingly. Conclusion Vendors were not aware of sustainable solid waste management measures existing at the market. However, vendors’ education levels and the duration of doing business at the market were related to their levels of awareness on SWM (p

Objective: To assess the impact of cessation of screening urine cultures on surgical site infection (SSI) incidence in clinical practice. Patients and Methods: Our study included patients undergoing hip replacement, knee replacement, spinal fusion, and laminectomy 12 months before (preintervention) and after (postintervention) cessation of preoperative screening urine cultures on June 1, 2017, at our institution. Urine cultures and urinalyses performed within 30 days before surgery during the 12 months before and after cessation were reviewed. SSI surveillance was performed in accordance with the methods of the National Healthcare Safety Network. Results: A total of 2754 patients were included (1286 preintervention and 1468 postintervention). In the preintervention period, 1141 urine cultures were performed, compared to 153 in the postintervention period; 35 and 6 episodes of asymptomatic bacteriuria were treated, respectively. The occurrence of SSI did not differ noticeably between time periods (1.2% vs 0.7%, P=.24), and quarterly incidences of SSI were unchanged. The rate of SSI was significantly lower in the postintervention period for laminectomy (3.0% vs 0.3%, P=.02). Conclusion: An 86.6% (153 vs 1141) reduction in screening urine cultures over a 12-month period was associated with a reduction of 988 unnecessary urine cultures, an 82.8% (6 vs 35) decline in inappropriate antibiotic treatment of asymptomatic bacteriuria, and no increase in SSI incidence after hip replacement, knee replacement, spinal fusion, or laminectomy procedures. No value of screening urine cultures before clean surgery was identified.

Abstract Spatial heterogeneities in soil hydrology have been confirmed as a key control on CO2 and CH4 fluxes in the Arctic tundra ecosystem. In this study, we applied a mechanistic ecosystem model, CLM‐Microbe, to examine the microtopographic impacts on CO2 and CH4 fluxes across seven landscape types in Utqiaġvik, Alaska: trough, low‐centered polygon (LCP) center, LCP transition, LCP rim, high‐centered polygon (HCP) center, HCP transition, and HCP rim. We first validated the CLM‐Microbe model against static‐chamber measured CO2 and CH4 fluxes in 2013 for three landscape types: trough, LCP center, and LCP rim. Model application showed that low‐elevation and thus wetter landscape types (i.e., trough, transitions, and LCP center) had larger CH4 emissions rates with greater seasonal variations than high‐elevation and drier landscape types (rims and HCP center). Sensitivity analysis indicated that substrate availability for methanogenesis (acetate, CO2 + H2) is the most important factor determining CH4 emission, and vegetation physiological properties largely affect the net ecosystem carbon exchange and ecosystem respiration in Arctic tundra ecosystems. Modeled CH4 emissions for different microtopographic features were upscaled to the eddy covariance (EC) domain with an area‐weighted approach before validation against EC‐measured CH4 fluxes. The model underestimated the EC‐measured CH4 flux by 20% and 25% at daily and hourly time steps, suggesting the importance of the time step in reporting CH4 flux. The strong microtopographic impacts on CO2 and CH4 fluxes call for a model‐data integration framework for better understanding and predicting carbon flux in the highly heterogeneous Arctic landscape.

Background: Conventionally grown fruits and vegetables (FVs) are the main source of general population exposure to pesticide residues. Objective: To evaluate the relation of intake of high- and low-pesticide-residue FVs with cancer risk. Methods: We followed 150,830 women (Nurses’ Health Study, 1998–2016, and Nurses’ Health Study II, 1999–2017) and 29,486 men (Health Professionals Follow-up Study, 1998–2016) without a history of cancer. We ascertained FV intake via validated food frequency questionnaires and categorized FVs as having high or low pesticide residue levels based on USDA surveillance data. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total and site-specific cancer related to quintiles of high- and low-pesticide-residue FV intake. Results: We documented 23,678 incident cancer cases during 2,862,118 person-years of follow-up. In the pooled multivariable analysis, neither high- nor low-pesticide-residue FV intake was associated with cancer. The HRs (95% CI) per 1 serving/day increase in intake were 0.99 (0.97–1.01) for high- and 1.01 (0.99–1.02) for low-pesticide-residue FVs. Additionally, we found no association between high-pesticide-residue FV intake and risk of specific sites, including malignancies previously linked to occupational pesticide exposure ([HR, 95% CI comparing extreme quintiles of intake] lung [1.17 (0.95–1.43)], non-Hodgkin lymphoma [0.89 (0.72–1.09)], prostate [1.31 (0.88–1.93)]) or inversely related to intake of organic foods (breasts [1.03 (0.94–1.31)]). Conclusions: These findings suggest that overall exposure to pesticides through FV intake is not related to cancer risk, although they do not rule out associations with specific chemicals or sub-types of specific cancers.

A code MolecGeom, based on algorithms for stepwise distortions of bond lengths, bond angles and dihedral angles of polyatomic molecules, is presented. Potential energy surfaces (PESs) are curated in terms of the energy for each molecular geometry. PESs based on the Born–Oppenheimer approximation, by which the atomic nuclei within a molecule are assumed stationary with respect to the motion of its electrons, are calculated. Applications requiring PESs involve the effects of nuclear motion on molecular properties. These include determining equilibrium geometries corresponding to stationary and saddle point energies, calculating reaction rates and predicting vibrational spectra. This multi-objective study focuses on the development of a new method for the calculation of PESs and the analysis of the molecular geometry components in terms of incremental changes that provide comprehensive sampling while preserving the precision of PES points. MolecGeom is applied to generate geometric data to calculate PESs for theoretical calculations of vibrational-rotational spectra of water and formaldehyde. An ab initio PES comprising 525 and 2160 intramolecular nuclear configurations results in vibrational frequencies in agreement with experiment, having errors less than 0.08% and 0.8%, respectively. Vinyl alcohol, with a total of 14 internal coordinates, generates a PES of 1458 unique geometries. Ascorbic acid, with 54 internal coordinates, generates a 1,899,776 point PES.

A persistent barrier to the cure and treatment of neurological diseases is the limited ability of the central and peripheral nervous systems to undergo neuroregeneration and repair. Recent efforts have turned to regeneration of various cell types through cellular reprogramming of native cells as a promising therapy to replenish lost or diminished cell populations in various neurological diseases. This review provides an in-depth analysis of the current viral vectors, genes of interest, and target cellular populations that have been studied, as well as the challenges and future directions of these novel therapies. Furthermore, the mechanisms by which cellular reprogramming could be optimized as treatment in neurological diseases and a review of the most recent cellular reprogramming in vitro and in vivo studies will also be discussed.

The Mediterranean diet has been associated with many health benefits. Therefore, we investigated whether the degree of adherence to the Mediterranean diet at baseline, or changes in adherence over time, were associated with the incidence of pre-frailty or frailty in generally healthy older adults. This study used the DO-HEALTH trial data. We evaluated Mediterranean diet adherence with Panagiotakos’ MedDietScore at baseline and at 3-year follow-up; frailty was assessed annually with the Fried frailty phenotype. We used minimally and fully adjusted mixed logistic regression models to estimate the exposure–disease relationship. We included 1811 participants without frailty at baseline (mean age 74.7 years; 59.4% women). Baseline adherence, as reflected by the MedDietScore, was not associated with becoming pre-frail [OR(95%CI) = 0.93 (0.83–1.03) for five-point greater adherence] or frail [OR(95%CI) = 0.90 (0.73–1.12) for five points]. However, a five-point increase in the MedDietScore over three years was associated with lower odds of becoming pre-frail [OR(95%CI) = 0.77 (0.68–0.88)] and frail [OR(95%CI) = 0.77 (0.64–0.92)]. In generally healthy and active older adults, baseline adherence to the Mediterranean diet was not associated with the incidence of pre-frailty or frailty over a 3-year follow-up. However, improved adherence to the Mediterranean diet over time was associated with significantly lower odds of becoming pre-frail or frail.

Kratom (Mitragyna speciosa, Korth.) is an evergreen tree that is indigenous to Southeast Asia. When ingested, kratom leaves or decoctions from the leaves have been reported to produce complex stimulant and opioid-like effects. For generations, native populations in Southeast Asia have used kratom products to stave off fatigue, improve mood, alleviate pain and manage symptoms of opioid withdrawal. Despite the long history of kratom use in Asia, it is only within the past 10–20 years that kratom has emerged as an important herbal agent in the United States, where it is being used for the self-treatment of pain, opioid withdrawal symptoms, and mood disorders. The increase in the use of kratom in the United States has coincided with the serious epidemic of opioid abuse and dependence. Since 2015, efforts to restrict access to prescription opioids have resulted in a marked increase in the use of “street” opioids such as heroin and illicit fentanyl. At the same time, many patients with chronic pain conditions or opioid use disorder have been denied access to appropriate medical help. The lack of access to care for patients with chronic pain and opioid use disorder has been magnified by the emergence of the COVID-19 pandemic. In this report, we highlight how these converging factors have led to a surge in interest in kratom as a potential harm reduction agent in the treatment of pain and opioid use disorder.