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Abstract World Health Organization (WHO) / Pan American Health Organization (PAHO) encouraged the utilization of whole-of-society and whole-of-government strategic approaches to increase countries’ resilience towards mitigating the impact of the COVID-19 pandemic. Strategies included the implementation of multi-sectoral, multi-partner and multi-stakeholder planning, coordination, consultation, and action. We reviewed the experiences of three Latin American and Caribbean countries, related to the implementation of collaborative strategies in tackling COVID-19, specifically the nature of the collaboration, the dynamics and the stakeholders involved. A systematic literature review identified relevant publications and content analysis was conducted to determine the collaborative strategies. Colombia, Costa Rica, and Trinidad and Tobago were selected as case studies since they were from different LAC subregions and because of the accessibility of relevant literature. In the three countries, the pandemic response was coordinated by a national executive committee, led by the Ministry of Health. Intersectoral collaboration was evident in each, with the key stakeholders being public sector agencies, the private/corporate sector, private/non-profit, academic institutions, and international agencies. It was used primarily to facilitate data-driven, evidenced-informed decision-making and guidelines; to expand clinical care capacity and strengthen the national medical response; and to provide support for the most vulnerable populations. While the institutionalization of intersectoral collaboration can be recommended for the health sector beyond the pandemic, research is needed to evaluate the impact of specific collaborative strategies as well as barriers and facilitators.

Abstract Regulation of codon optimality is an increasingly appreciated layer of cell- and tissue-specific protein expression control. Here, we use codon-modified reporters to show that differentiation of Drosophila neural stem cells into neurons enables protein expression from rare-codon-enriched genes. From a candidate screen, we identify the cytoplasmic polyadenylation element binding (CPEB) protein Orb2 as a positive regulator of rare-codon-dependent mRNA stability in neurons. Using RNA sequencing, we reveal that Orb2-upregulated mRNAs in the brain with abundant Orb2 binding sites have a rare-codon bias. From these Orb2-regulated mRNAs, we demonstrate that rare-codon enrichment is important for mRNA stability and social behavior function of the metabotropic glutamate receptor (mGluR). Our findings reveal a molecular mechanism by which neural stem cell differentiation shifts genetic code regulation to enable critical mRNA stability and protein expression.

Translocation of captive-bred animals is a widely used conservation strategy to support the recovery of imperiled wild populations. Identifying which factors enhance or limit survival after release can be important in adapting translocation strategies, particularly for species with low survival rates after release from captivity. Many translocation programs track post-translocation survival, but few complete spatial-statistical assessments of mortality risk associated with release environments. Typically, few animals are released from captive breeding programs, limiting the sample size available for analyses. We aimed to create a workflow that used limited datasets to evaluate the influence of spatial conditions and other factors on mortality risk. Greater sage-grouse (Centrocercus urophasianus) are endangered in Canada and of conservation concern throughout their range in the United States. After the species declined precipitously in Canada, a captive breeding program was initiated with subsequent releases in Alberta and Saskatchewan. Despite success in captive breeding, mortality rates of released sage-grouse were high. We used GPS- and VHF-based locations of released sage-grouse to determine how spatial features influence mortality risk of sage-grouse after release from captivity. We implemented a multistep approach to quantify and map risk relative to the environmental features associated with mortality. We also assessed whether the movement behaviors of sage-grouse correspond with environmental risk factors by using a combination of survival models and integrated step-selection functions. Mortality of sage-grouse in Alberta was hastened in areas close to anthropogenic disturbance. Although birds in Alberta avoided areas of higher mortality risk, those in Saskatchewan did not, perhaps due to environmental and selection constraints. This multistep approach allowed us to utilize small sample sizes to assess key risk factors in the landscape. This process supports the adaptive modification of translocation plans and can similarly support other data-limited scientists and managers in assessing environmental mortality risk and defining conservation actions for endangered species.

Tropical cyclones (TCs) are extreme meteorological events that cause significant deaths, infrastructure damage, and financial losses around the world. In recent years, the Eastern Highlands of Zimbabwe's have become increasingly vulnerable to TCs caused by Indian Ocean tropical cyclones making landfall more frequently. There is still a limited understanding of the phenomenon and the quantification of its impacts. The aim of this research is to conduct a comparative analysis of the variability in the severity of tropical cyclones by analysing historical storm tracks and mapping the environmental impacts in Zimbabwe's Chimanimani and Chipinge districts. Results indicate that, between 1945 and 2022, the Eastern Highlands of Zimbabwe experienced 5 of the total 865 cyclones in the Southwest Indian Ocean. The maximum sustained winds from the Cyclone Idai in the Eastern Highlands were recorded as 195 km/h. Some of the remote sensing-based indices used to extract spatial information about the condition of vegetation, wetlands, built-up area, and bar land during pre and post cyclonic events included the Normalized Difference Vegetation Index (NDVI) and Modified Normalized Difference Water Index (MNDWI). Analysis of NDVI in the Eastern Highlands revealed that there was a significant decrease in vegetated area because of the cyclone impact, with a decrease of 2.1% and 16.68% for cyclone Japhet and Idai respectively. The MNDWI shows a 10.74% increase in water content after cyclone Eline. Field validation in 2019 confirms the research findings. An Operations Dashboard Disaster Management System was developed in order to disseminate information to the affected stakeholders about the potential risk that the face due to the occurrence of the natural phenomena.

Abstract Brain-computer interfaces have so far focused largely on enabling the control of a single effector, for example a single computer cursor or robotic arm. Restoring multi-effector motion could unlock greater functionality for people with paralysis (e.g., bimanual movement). However, it may prove challenging to decode the simultaneous motion of multiple effectors, as we recently found that a compositional neural code links movements across all limbs and that neural tuning changes nonlinearly during dual-effector motion. Here, we demonstrate the feasibility of high-quality bimanual control of two cursors via neural network (NN) decoders. Through simulations, we show that NNs leverage a neural ‘laterality’ dimension to distinguish between left and right-hand movements as neural tuning to both hands become increasingly correlated. In training recurrent neural networks (RNNs) for two-cursor control, we developed a method that alters the temporal structure of the training data by dilating/compressing it in time and re-ordering it, which we show helps RNNs successfully generalize to the online setting. With this method, we demonstrate that a person with paralysis can control two computer cursors simultaneously. Our results suggest that neural network decoders may be advantageous for multi-effector decoding, provided they are designed to transfer to the online setting.

The effects of acid and alkali hydrolysis, as well as rice husk varieties (pure and mixed), on bioethanol production using saccharification and fermentation, were investigated in this study. Microbes such as Saccharomyces cerevisiae are currently used for fermenting agricultural wastes to bioethanol, an environmentally friendly alternative to petroleum energy sources. Rice husks were ground to a fine powder, then hydrolyzed with acid and alkali, and incubated for five days. A refractometer was used to perform a sugar reduction test, which determined the presence of fermentable sugar in the media. The parameters revealed that the variety of rice husk used did not affect the ethanol percent yield, which was 14.8 ± 0.5% and 15.0 ± 0.5% for the pure and mixed varieties, respectively; however, there was a substantial difference in the percentage yield in the method of pre-treatment. The percentage yield of ethanol in the acid pre-treated sample was higher (14.8 ± 0.5% and 15.0 ± 0.5%) than that of the alkali (6.1 ± 0.5% and 4.8 ± 0.5%). The presence of alcohol in the sample was confirmed by FTIR analysis, while GC-MS identified the specific compounds and their percentage composition - ethanol (9.67%). This suggests that using H2SO4 in the hydrolysis of rice husk is a promising and effective method for producing bioethanol.

Objective: Tools that quantify tissue perfusion of the foot are deficient, contributing to the uncertainty in predicting ulcer healing potential. This pilot study aims to quantify peri-wound foot perfusion at various tissue depths using a novel application of pseudo-continuous arterial spin labeling magnetic resonance imaging. Methods: Ten diabetic patients with neuropathic wounds and 20 healthy volunteers without wounds were recruited. Wounds were graded according to the Wound, Ischemia, Foot Infection (WIfI) system. All subjects underwent a noncontrasted ASL MRI of the foot for perfusion measurements. For healthy volunteers, perfusion was compared at rest and during sustained toe flexion between four regions: lateral plantar, medial plantar, lateral calcaneal, and medial calcaneal. Evaluations of diabetic volunteers compared perfusion between four zones: wound, near border, far border, and remote. Remote zone perfusion in diabetics was compared with perfusion in the plantar foot of healthy volunteers. Results: There were 11 wounds, which were located over the metatarsal heads in five, the stump of a transmetatarsal amputation in three, the heel in two, and the mid foot in one. The median WIfI stage was 2. One patient had a WIfI ischemia grade of 1; the remaining patients’ grades were 0. The mean ankle-brachial index was 1.0 ± 0.3. There were two patients with a WIfI foot infection grade of 1; the remaining patients’ grades were 0. In healthy volunteers, plantar foot perfusion with sustained toe flexion was 43.9 ± 1.7 mL/100g/min and significantly higher than perfusion at rest (27.3 ± 2.7 mL/100g/min; P < .001). In diabetic patients, perfusion at the wound, near border, far border, and remote regions was 96.1 ± 10.7, 92.7 ± 9.4, 73.4 ± 8.2, and 62.8 ± 2.7 mL/100g/min. Although this perfusion pattern persisted throughout the depth of the wound, perfusion decreased with tissue depth. In the near border, perfusion at 20% of the wound depth was 124.0 ± 35.6 mL/100g/min and 69.9 ± 10.1 mL/100g/min at 100% (P = .006). Lastly, remote perfusion in diabetics was 2.3 times the plantar perfusion in healthy volunteers (27.3 ± 2.7 mL/100g/min; P < .001). Conclusions: The pattern of resting tissue perfusion around nonischemic diabetic foot ulcers was successfully quantified with arterial spin labeling magnetic resonance imaging. Diabetic patients with wounds were hyperemic compared with healthy volunteers. There was a 1.5-fold increase in peri-wound tissue perfusion relative to the rest of the foot. This study is the first step in developing a tool to assess the perfusion deficit in ischemic wounds.

Quantitative estimates of amount of groundwater resources are required in the transboundary Tuli Karoo Basin to better manage and promote sustainable conjunctive use of the aquifer. Unfortunately, such important data and information are lacking. The aim of this study was to map groundwater potential zones and model groundwater recharge as well as groundwater flow in the Tuli Karoo Basin (12,164 km2) using geospatial techniques. To delineate groundwater potential zones, nine thematic maps of groundwater conditioning factors were computed and weighted using Saaty's Analytical Hierarchy Process (AHP). To validate the groundwater potential map, a Kruskal–Wallis test was performed. Groundwater recharge and groundwater flow direction were estimated in a coupled Geographic Information System (GIS) and modelling environment using the soil–water–balance model (SWB) and British Geological Survey (BGS) groundwater tool, respectively. Results for groundwater potential mapping showed that the area is dominated by high ground water potential which covers about 57.8% (6,915.1 km2) of the basin. The Kruskal–Wallis test showed that the median values of the borehole yields vary significantly between the different groundwater potential zone classes (P-value

Diurnal basking (“sunning”) is common in many ectotherms and is generally thought to be a behavioural mechanism for thermoregulation. Recent studies have reported the occurrence of nocturnal basking in a few distantly-related species of freshwater turtles, but the true extent of this behaviour is unknown, and it may be underreported due to sampling biases (e.g., not surveying for turtles at night). Therefore, we initiated a global, collaborative effort to systematically document and quantify basking activity (diurnal and nocturnal) across a wide range of freshwater turtle species and locations. We conducted camera trap or manual surveys in North America, the Caribbean, Europe, Asia, Africa, the Seychelles, and Australia. We collected 873,111 trail camera photographs (25,273 hrs of search effort) and obtained data on 29 freshwater turtle species from seven families. Nocturnal basking was documented in 13 species, representing six families (Chelidae, Emydidae, Geoemydidae, Kinosternidae, Pelomedusidae, and Trionychidae), including representatives in Central America, Trinidad and Tobago, Africa, the Seychelles, Asia, and Australia. Nocturnal basking was restricted to tropical and sub-tropical locations, suggesting that environmental temperature plays a role in this behaviour. However, the primary factors driving nocturnal basking are yet to be determined and may vary geographically and by species. The frequency and duration of nocturnal basking varied among species and seasons, but nocturnal basking events were often substantially longer than diurnal events. This is the first study to document a widespread occurrence of nocturnal basking, and our results suggest that nocturnal basking may be a common, although overlooked, aspect of many species’ ecology.

Groundwater provides critical freshwater supplies for most rural communities living in drought-prone areas. Such is the case for Runde catchment in Zimbabwe, whose rural communities depend on groundwater. Climate change and increased variability pose a threat to water availability by affecting groundwater potential and recharge, but the full extent of the threat is not well understood. Thus, the main objective of this study was to assess the impact of climate change on groundwater potential and recharge in the catchment. The groundwater potential mapping was performed using a spatially weighted overlay method with inputs: soil type, geology, land use, observed precipitation, topographic wetness index and elevation. This mapping produced a groundwater potential index, classified into groundwater potential zones and cross-validated with borehole yield data, r=0.63 and n=62. The groundwater potential validation showed 1.6 and 4.8% of the total boreholes were in the high (>7 L/s) to very high (4–7 L/s) while 43.5 and 50.1% moderate (1–4 L/s), and low (

As both a sensor of extracellular calcium (Ca2+o) concentration and a key controller of Ca2+o homeostasis, one of the most interesting properties of the calcium-sensing receptor (CaR) is its sensitivity to, and modulation by, ions and small ligands other than Ca2+. There is emerging evidence that extracellular phosphate can act as a partial, non-competitive CaR antagonist to modulate parathyroid hormone (PTH) secretion, thus permitting the CaR to integrate mineral homeostasis more broadly. Interestingly, phosphorylation of certain intracellular CaR residues can also inhibit CaR responsiveness. Thus, negatively charged phosphate can decrease CaR activity both extracellularly (via association with arginine) and intracellularly (via covalent phosphorylation).

Effective monitoring tools are key for tracking biodiversity loss and informing management intervention strategies. Passive acoustic monitoring promises to provide a cheap and effective way to monitor biodiversity across large spatial and temporal scales, however, extracting useful information from long-duration audio recordings still proves challenging. Recently, a range of acoustic indices have been developed, which capture different aspects of the soundscape, and may provide a way to estimate traditional biodiversity measures. Here we investigated the relationship between 13 acoustic indices obtained from passive acoustic monitoring and biodiversity estimates of various vertebrate taxonomic groupings obtained from manual surveys at six sites spanning over 20 degrees of latitude along the Australian east coast. We found a number of individual acoustic indices that correlated well with species richness, Shannon’s diversity index, and total individual count estimates obtained from traditional survey methods. Correlations were typically greater for avian and total vertebrate biodiversity than for anuran and non-avian vertebrate biodiversity. Acoustic indices also correlated better with species richness and total individual count than with Shannon’s diversity index. Random forest models incorporating multiple acoustic indices provided more accurate predictions than single indices alone. Out of the acoustic indices tested, cluster count, mid-frequency cover and spectral density contributed the greatest predictive ability to models. Our results suggest that models incorporating multiple acoustic indices could be a useful tool for monitoring certain vertebrate groups. Further work is required to understand how site-specific variables can be incorporated into models to improve predictive capabilities and how to improve the monitoring of taxa besides avians, particularly anurans.

Echinococcus spp. tapeworms can cause serious diseases in mammals, including humans. Within the E. granulosus species complex, metacestodes produce unilocular cysts that are responsible for cystic echinococcosis in animal intermediate hosts. Canids are definitive hosts, harbouring adult cestodes in their intestines. Adult E. canadensis were recovered from the small intestine of 1 of 262 coyotes (Canis latrans) from Nova Scotia, Canada. Subsequently, we found unilocular cysts in lungs and livers of 4 of 8 sympatric moose (Alces alces) from Cape Breton Island. DNA was extracted from three cysts using the Qiagen DNeasy Blood and Tissue kit and assayed by polymerase chain reaction (PCR) with primers (cest4 and cest5) for a 117-bp region of the small subunit of ribosomal RNA of E. granulosus sensu lato, and further validated as E. canadensis G8 using primers targeting nicotinamide adenosine dinucleotide dehydrogenase subunit 1 (ND1) and cytochrome c oxidase subunit 1 (CO1) mitochondrial genes. These are the first records of E. canadensis in any of the three Maritime provinces, which include Nova Scotia, New Brunswick, and Prince Edward Island. The parasite was thought to be absent in this region due to extirpation of wolves (Canis spp.) in the 1800s. These findings suggest that further wildlife surveillance and risk assessment is warranted.

Globally, river regulation has degraded wetlands, including parts of the Murray-Darling Basin (MDB), an ecologically significant basin in Australia. Frogs in a floodplain environment largely depend on habitats created by river flows, but little is known about how frogs in the northern MDB are impacted by river regulation. We tested how wetland inundation affected frogs in a catchment of the northern MDB. We surveyed frogs between 2015 and 2019 to determine long-term changes in the community composition associated with wetland inundation from river flows. Additionally, we recorded nightly soundscapes for four days before and after the arrival of river flows between 2019 and 2020. The abundance and richness of frog species increased during larger inundation events leading to altered community composition (beta diversity). Warmer temperatures increased frog species richness, and frog community dominance decreased with decreasing vegetation cover (i.e., the relative abundance became more even across species). The abundance of five frog species (Limnodynastes tasmaniensis, Limnodynastes fletcheri, Crinia parinsignifera, Litoria peronii, and Litoria latopalmata) was higher in response to increased inundation extent. The total species richness of chorusing frogs increased after the arrival of river flows; six species chorused over the four nights preceding flow, whereas eight species chorused following the flow arrival, but the responses varied among species and sites. Frog species richness increased at three sites after flows, but not at others. After inundation, the choruses of Limnodynastes tasmaniensis increased whereas Limnodynastes fletcheri decreased. Our findings indicate that wetland inundation is beneficial for frog communities and suggest that chorusing behaviour varied in response to river flows inundating floodplain wetlands.

Post-traumatic stress disorder (PTSD) is a devastating disorder that involves maladaptive changes in immune status. Using the stress-enhanced fear learning (SEFL) paradigm, an animal model of PTSD, our laboratory has demonstrated increased pro-inflammatory cytokine immunoreactivity in the hippocampus following severe stress. Recent clinical trials have demonstrated 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy as an effective novel treatment for PTSD. Interestingly, MDMA has been shown to have an immunosuppressive effect in both pre-clinical and clinical studies. Therefore, we predict MDMA administration may attenuate SEFL, in part, due to an immunosuppressive mechanism. The current studies test the hypothesis that MDMA is capable of attenuating SEFL and inducing alterations in expression of TNF-α, IL-1β, glial fibrillary acidic protein (GFAP), an astrocyte specific marker, and ionized calcium-binding adapter molecule −1 (IBA-1), a microglial specific marker, in the dorsal hippocampus (DH) following a severe stressor in male animals. To this end, experiment 1 determined the effect of MDMA administration 0, 24, and 48 h following a severe foot shock stressor on SEFL. We identified that MDMA administration significantly attenuated SEFL. Subsequently, experiment 2 determined the effect of MDMA administration following a severe stressor on the expression of TNF-α, IL-1β, GFAP, and IBA-1 in the DH. We found that MDMA administration significantly attenuated stress-induced IL-1β and stress-reduced IBA-1 but had no effect on TNF-α or GFAP. Overall, these results support the hypothesis that MDMA blocks SEFL through an immunosuppressive mechanism and supports the use of MDMA as a potential therapeutic agent for those experiencing this disorder. Together, these experiments are the first to examine the effect of MDMA in the SEFL model and these data contribute significantly towards the clinical PTSD findings.

Abstract Leaving the water to bask (usually in the sun) is a common behavior for many freshwater turtles, with some species also engaging in “nocturnal basking.” Ectoparasite removal is an obvious hypothesis to explain nocturnal basking and has also been proposed as a key driver of diurnal basking. However, the efficacy of basking, day or night, to remove leeches has not been experimentally tested. Therefore, we examined the number of leeches that were removed from Krefft's river turtles (Emydura macquarii krefftii) after experimentally making turtles bask at a range of times of day, durations, and temperatures. Turtles had high initial leech loads, with a mean of 32.1 leeches per turtle. Diurnal basking under a heat lamp for 3 hr at ~28°C significantly reduced numbers of leeches relative to controls. In diurnal trials, 90.9% of turtles lost leeches (mean loss of 7.1 leeches per turtle), whereas basking for 30 min under the same conditions was not effective (no turtles lost leeches, and all turtles were still visibly wet). Similarly, “nocturnal basking” at ~23°C for 3 hr was not effective at removing leeches. Only 18% of turtles lost leeches (one turtle lost one leech and another lost four leeches). Diurnal basking outdoors under direct sunlight for 20 min (mean temp = 34.5°C) resulted in a small reduction in leeches, with 50% of turtles losing leeches and an average loss of 0.7 leeches per turtle. These results indicate basking can remove leeches if temperatures are high or basking durations are long. However, it was only effective at unusually long basking durations in this system. Our data showed even the 20‐min period was longer than 70.1% of natural diurnal basking events, many of which took place at cooler temperatures. Therefore, leech removal does not appear to be the purpose of the majority of basking events.

Abstract Background We aimed to systematically describe the burden and distribution of white matter hyperintensities (WMH) and investigate correlations with neuropsychiatric symptoms in pathologically proven Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). Methods Autopsy-confirmed cases were identified from the Sunnybrook Dementia Study, including 15 cases of AD and 58 cases of FTLD (22 FTLD-TDP cases; 10 FTLD-Tau [Pick’s] cases; 11 FTLD-Tau Corticobasal Degeneration cases; and 15 FTLD-Tau Progressive Supranuclear Palsy cases). Healthy matched controls (n = 35) were included for comparison purposes. Data analyses included ANCOVA to compare the burden of WMH on antemortem brain MRI between groups, adjusted linear regression models to identify associations between WMH burden and neuropsychiatric symptoms, and image-guided pathology review of selected areas of WMH from each pathologic group. Results Burden and regional distribution of WMH differed significantly between neuropathological groups (F 5,77 = 2.67, P’ = 0.029), with the FTLD-TDP group having the highest mean volume globally (8032 ± 8889 mm3) and in frontal regions (4897 ± 6163 mm3). The AD group had the highest mean volume in occipital regions (468 ± 420 mm3). Total score on the Neuropsychiatric Inventory correlated with bilateral frontal WMH volume (β = 0.330, P = 0.006), depression correlated with bilateral occipital WMH volume (β = 0.401, P < 0.001), and apathy correlated with bilateral frontal WMH volume (β = 0.311, P = 0.009), all corrected for the false discovery rate. Image-guided neuropathological assessment of selected cases with the highest burden of WMH in each pathologic group revealed presence of severe gliosis, myelin pallor, and axonal loss, but with no distinguishing features indicative of the underlying proteinopathy. Conclusions These findings suggest that WMH are associated with neuropsychiatric manifestations in AD and FTLD and that WMH burden and regional distribution in neurodegenerative disorders differ according to the underlying neuropathological processes.

Abstract Emerging infectious diseases are a serious threat to wildlife populations, and there is growing evidence that host microbiomes play important roles in infection dynamics, possibly even mitigating diseases. Nevertheless, most research on this topic has focused only on bacterial microbiomes, while fungal microbiomes have been largely neglected. To help fill this gap in our knowledge, we examined both the bacterial and fungal microbiomes of four sympatric Australian frog species, which had different population‐level responses to the emergence of chytridiomycosis, a widespread disease caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). We sequenced 16,884 fungal amplicon sequence variants (ASVs) and 41,774 bacterial ASVs. Bacterial communities had higher richness and were less variable within frog species than were fungal communities. Nevertheless, both communities were correlated for both ASV richness and beta diversity (i.e., frogs with similar bacterial richness and community composition tended to also have similar fungal richness and community composition). This suggests that either one microbial community was having a large impact on the other or that they were both being driven by similar environmental factors. For both microbial taxa, we found little evidence of associations between Bd (prevalence or intensity) and either individuals' ASVs or beta diversity. However, there was mixed evidence of associations between richness (both bacterial and fungal) and Bd, with high richness potentially providing a protective effect. Surprisingly, the relative abundance of bacteria that have previously been shown to inhibit Bd was also positively associated with Bd infection intensity, suggesting that a high relative abundance of those bacteria provides poor protection against infection.

Codon usage bias has long been appreciated to influence protein production. Yet, relatively few studies have analyzed the impacts of codon usage on tissue-specific mRNA and protein expression. Here, we use codon-modified reporters to perform an organism-wide screen in Drosophila melanogaster for distinct tissue responses to codon usage bias. These reporters reveal a cliff-like decline of protein expression near the limit of rare codon usage in endogenously expressed Drosophila genes. Near the edge of this limit, however, we find the testis and brain are uniquely capable of expressing rare codon-enriched reporters. We define a new metric of tissue-specific codon usage, the tissue-apparent Codon Adaptation Index (taCAI), to reveal a conserved enrichment for rare codon usage in the endogenously expressed genes of both Drosophila and human testis. We further demonstrate a role for rare codons in an evolutionarily young testis-specific gene, RpL10Aa. Optimizing RpL10Aa codons disrupts female fertility. Our work highlights distinct responses to rarely used codons in select tissues, revealing a critical role for codon bias in tissue biology.

Background:. Pyogenic flexor tenosynovitis (PFT) is frequently diagnosed by physical examination according to the Kanavel signs. This study proposes a modification of the Kanavel sign “tenderness over the course of the flexor sheath” by including palpation of the A1 pulley to increase specificity for diagnosis. Methods:. A retrospective review was performed over 8 months for patients in the emergency department who received a consult to hand surgery to rule out PFT. Two cohorts, nonPFT infections and PFT infections, were studied for the presence or absence of the four Kanavel signs, as well as tenderness specifically over the A1 pulley on the affected digit(s) or T1 pulley of the thumb. Results:. There were a total of 33 patients in the two cohorts (21 nonPFT, 12 PFT) with statistically significant differences with regard to the presence of all the Kanavel signs. A1 pulley tenderness had the greatest odds ratio, positive predictive value, specificity, and accuracy when compared with all Kanavel signs. When used in conjunction with each Kanavel sign, there was an increase in specificity in all four signs. Receiver operating characteristic analysis revealed increased area under the curve with A1 pulley tenderness added, indicating improved ability to classify hand infections as PFT versus nonPFT. Conclusion:. Although the classic Kanavel signs have shown reliable clinical utility, this study finds that tenderness at the A1 pulley can be a useful specification of “tenderness over the course of the flexor sheath” to help with the diagnosis of PFT.

How the abrupt warming events recorded in Greenland ice cores during the last glacial cycle have influenced the tropical climate is not well known. Here the authors present new lake sediment data from the Peruvian Andes that shows that these events resulted in rapid glacier retreat and large reductions in lake level.

Ranaviral infections have been associated with mass mortality events in captive and wild amphibian, fish, and reptile populations globally. In Australia, two distinct types of ranaviruses have been isolated: epizootic haematopoietic necrosis virus in fish and a Frog virus 3-like ranavirus in amphibians. Experimental studies and serum surveys have demonstrated that several Australian native fish, amphibian, and reptile species are susceptible to infection and supported the theory that ranavirus is naturally circulating in Australian herpetofauna. However, ranaviral infections have not been detected in captive or wild lizards in Australia. Oral-cloacal swabs were collected from 42 wild lizards from northern Queensland and 83 captive lizards from private collections held across three states/territories. Samples were tested for ranaviral DNA using a quantitative PCR assay. This assay detected ranaviral DNA in 30/83 (36.1%) captive and 33/42 (78.6%) wild lizard samples. This is the first time molecular evidence of ranavirus has been reported in Australian lizards.

Aortoesophageal fistula (AEF) is a rare complication of esophageal interventions. We present a 49-year-old woman who underwent Roux-en-Y gastric bypass with a recurrent gastrojejunal anastomotic leak requiring covered esophageal stent placement. She presented 1 month later with abdominal pain, leukocytosis, and hematemesis. A computed tomography scan demonstrated migration of the esophageal stent with aortic erosion concerning for AEF. She underwent emergent endovascular exclusion of an AEF to the descending thoracic aorta with subsequent esophageal resection and diversion and aortic endograft explant, resection, and homograft repair on postoperative day 6 allowing for staged removal of prosthetic material and maintenance of inline flow.

Abstract Background Supernumerary ORFan genes (i.e., open reading frames without obvious homology to other genes) are present in the mitochondrial genomes of gonochoric freshwater mussels (Bivalvia: Unionida) showing doubly uniparental inheritance (DUI) of mitochondria. DUI is a system in which distinct female-transmitted and male-transmitted mitotypes coexist in a single species. In families Unionidae and Margaritiferidae, the transition from dioecy to hermaphroditism and the loss of DUI appear to be linked, and this event seems to affect the integrity of the ORFan genes. These observations led to the hypothesis that the ORFans have a role in DUI and/or sex determination. Complete mitochondrial genome sequences are however scarce for most families of freshwater mussels, therefore hindering a clear localization of DUI in the various lineages and a comprehensive understanding of the influence of the ORFans on DUI and sexual systems. Therefore, we sequenced and characterized eleven new mitogenomes from poorly sampled freshwater mussel families to gather information on the evolution and variability of the ORFan genes and their protein products. Results We obtained ten complete plus one almost complete mitogenome sequence from ten representative species (gonochoric and hermaphroditic) of families Margaritiferidae, Hyriidae, Mulleriidae, and Iridinidae. ORFan genes are present only in DUI species from Margaritiferidae and Hyriidae, while non-DUI species from Hyriidae, Iridinidae, and Mulleriidae lack them completely, independently of their sexual system. Comparisons among the proteins translated from the newly characterized ORFans and already known ones provide evidence of conserved structures, as well as family-specific features. Conclusions The ORFan proteins show a comparable organization of secondary structures among different families of freshwater mussels, which supports a conserved physiological role, but also have distinctive family-specific features. Given this latter observation and the fact that the ORFans can be either highly mutated or completely absent in species that secondarily lost DUI depending on their respective family, we hypothesize that some aspects of the connection among ORFans, sexual systems, and DUI may differ in the various lineages of unionids.

Objectives and importance of study: The importance of health policy and systems research (HPSR) has been acknowledged since 2004 and was recognised by the United Nations World Health Assembly in 2005. However, many factors influence its development. This paper aims to analyse the impact of politics and political determinants on HPSR funding in selected countries of Latin America and the Caribbean. Methods: Using a standardised protocol, we performed an analysis of available data and financing structures for health research and HPSR, based on research in eight countries, including interviews with key stakeholders (n = 42). Results: Dollar depreciation and gross national product growth in the region may play a role in how governments fund research. There have been shifts in the political spectrum in governments, which have affected research coordination and funding in positive and negative ways. HPSR funding in some countries was dependent on budget decisions and although some have improved funding, others have regressed by decreasing funding or have completely cancelled financing mechanisms. Caribbean countries rely mainly on institutional funding. HPSR is recognised as important but remains underfunded; stakeholders believed it should be used more in decision making. Conclusion: Although HPSR is recognised as valuable for decision making and policy development, it does not have the financial support required to flourish in Latin America and the Carribean. Data on health research financing were not easy to access. There was little or no evidence of published reports or papers about research financing, health research funding, and HPSR funding in particular in the studied countries. Because of the fragility of health systems highlighted by the coronavirus disease 2019 (COVID-19) pandemic, HPSR should be of great relevance and value to both policy makers and funders.

Zein can be utilized to form nanoscale particles for drug delivery applications. Despite the ease of synthesis, these particles often aggregate when exposed to physiologically relevant conditions (e.g., pH and salt concentrations). This instability has prevented their further development in applications requiring intravenous administration. To mitigate this colloidal instability, this research explored Zein nanoparticles (NP)s that were modified with polyethylene glycol (PEG) either through functionalized PEG pre- or post-NP formation. The results suggest that the pre-functionalization of the Zein using N-hydroxysuccinimide ester terminated PEG is the method of choice for synthesizing Zein NPs with conjugated PEG (Zein:PEG-Zein NPs). Zein:PEG-Zein NPs formed using this method displayed excellent stability in physiologically relevant conditions over 72 h and were stable at 4 °C for at least 3 months. When the NPs were cultured with cells for 72 h, no cytotoxicity or early signs of apoptosis were identified. Cellular uptake of the Zein:PEG-Zein NPs did not seem to be impacted by the amount of PEG incorporated in the NP but were concentration-, time-, and temperature-dependent. The lowest percent, stable Zein:PEG-Zein NP formulation (80% unmodified Zein and 20% PEG-modified Zein) induced no observable toxicity over 14 days in CD-1 mice dosed at 70 mg/kg via the tail vein. However, repeat dose pharmacokinetic (PK) studies demonstrated that following the first dose, the second dose caused health issues that required euthanasia shortly after administration. For those animals that survived, there was faster plasma elimination of the Zein:PEG-Zein NPs. Despite this, the Zein:PEG-Zein NPs represent a significantly improved formulation approach, one that displays a long circulation half-life and is suitable for single-use administration. Repeat dose applications will require additional methods to silence the immune response that is generated when using these NPs intravenously.

Elevated inorganic phosphate levels promote excessive parathyroid hormone secretion, which contributes to the aetiology of secondary hyperparathyroidism. Here, the authors show that phosphate directly inhibits the calcium-sensing receptor, the main regulator of parathyroid hormone secretion.

Abstract Background There is limited information regarding Descemet stripping automated endothelial keratoplasty (DSAEK) for endothelial failure secondary to cytomegalovirus (CMV) endotheliitis. Treatment is difficult with high recurrence rates. We describe a case when systemic valganciclovir therapy is directed by aqueous CMV-DNA levels, leading to good graft survival. Findings A 59-year-old male with bilateral CMV endotheliitis despite antiviral therapy developed endothelial failure and underwent DSAEK. Prior to surgery, aqueous polymerase chain reaction (PCR) for CMV was repeatedly performed, where CMV-positive episodes were treated with systemic valganciclovir. Monthly aqueous analysis was performed until CMV-DNA was undetectable before DSAEK was performed. Post-operative prophylactic systemic valganciclovir treatment was instituted and switched to topical valganciclovir treatment when aqueous samples were negative for CMV. Conclusion Targeted aqueous sampling for CMV-DNA perioperatively guides antiviral therapy and ensures adequacy of treatment, minimising the duration of systemic valganciclovir therapy to reduce adverse effects of long-term treatment.

Signal transduction pathways are intricately fine-tuned to accomplish diverse biological processes. An example is the conserved Ras/mitogen-activated-protein-kinase (MAPK) pathway, which exhibits context-dependent signaling output dynamics and regulation. Here, by altering codon usage as a novel platform to control signaling output, we screened the Drosophila genome for modifiers specific to either weak or strong Ras-driven eye phenotypes. Our screen enriched for regions of the genome not previously connected with Ras phenotypic modification. We mapped the underlying gene from one modifier to the ribosomal gene RpS21. In multiple contexts, we show that RpS21 preferentially influences weak Ras/MAPK signaling outputs. These data show that codon usage manipulation can identify new, output-specific signaling regulators, and identify RpS21 as an in vivo Ras/MAPK phenotypic regulator.

Background:. The COVID-19 global pandemic has impacted plastic surgery training in the United States, requiring unprecedented measures to prepare for potential surges in critically ill patients. This study investigates how plastic surgery programs responded to this crisis, as well as how successful these changes were, through a survey of program directors and of residents at academic training programs in the United States. Methods:. Two separate anonymous online surveys were conducted via REDCap between April 16 and June 4, 2020. The first survey was distributed to program directors, and the second was distributed to plastic surgery residents. Resident responses were then subdivided for an analysis between geographic regions. Results:. Of the 59 program director responses (43.7%), the majority of programs implemented a platoon approach for resident coverage. A minority did the same for attending coverage. In total, 92% transitioned to virtual didactics only. Plastic surgery residents covered alternative services at 25% of responding institutions, and an additional 68% had a plan in place for responding to personnel shortages. Overall, residents were satisfied with their program’s response in a variety of categories. When subdivided based on geographic region, respondents in the Northeast and Northwest were less satisfied with resident wellness, personal and loved ones’ safety, and program communication. Conclusions:. With the possibility of a “second wave,” successful methods of academic programs adapting to the pandemic should be communicated to reduce the future impact. Increased frequency of communications between program directors and residents can improve mental health and wellness of the resident population.

Benzene, toluene, ethylbenzene and xylene, also known as BTEX, are released into environmental media by petroleum product exploratory and exploitative activities and are harmful to humans and animals. Testing the effects of these chemicals on a significantly large scale requires an inexpensive, rapidly developing model organism such as Drosophila melanogaster. In this study, the toxicological profile of benzene, toluene, ethylbenzene, p-xylene, m-xylene, and o-xylene in D. melanogaster was evaluated. Adult animals were monitored for acute toxicity effects. Similarly, first instar larvae reared separately on the same compounds were monitored for the ability to develop into adult flies (eclosion). Further, the impact of fixed concentrations of benzene and xylene on apoptosis and mitosis were investigated in adult progenitor tissues found in third instar larvae. Toluene is the most toxic to adult flies with an LC50 of 0.166 mM, while a significant and dose-dependent decrease in fly eclosion was observed with benzene, p-xylene, and o-xylene. An increase in apoptosis and mitosis was also observed in animals exposed to benzene and p-xylene. Through Genome Wide Association Screening (GWAS), 38 regions of the D. melanogaster genome were identified as critical for responses to p-xylene. This study reveals the strength of D. Melanogaster genetics as an accessible approach to study BTEX compounds.