Determining the Optimal Intramedullary Screw Canal Fill Ratio in Length Unstable Metacarpal Fractures: A Biomechanical Investigation.

PURPOSE: Intramedullary (IM) screw fixation is gaining popularity in the treatment of metacarpal fractures. Despite its rapid adoption, there is a paucity of evidence regarding parameters to optimize effectiveness. This study aimed to quantify the relationship between stability, IM screw size, and canal fill using a cadaveric model. METHODS: Thirty cadaveric metacarpals (14 index, 13 middle, and three ring fingers; mean age: 58.3 years, range: 48-70) were selected to allow for canal fill ratios of 0.7-1.1 for screws sized 3.0, 3.5, and 4.5 mm. Metacarpals underwent a 45° volar-dorsal osteotomy at the midpoint before fixation with an IM screw. Specimens were subjected to 100 cycles of loading at 10 N, 20 N, and 30 N before load-to-failure testing. Correlation coefficients for angular displacement on the final cycle at each load, peak load to failure, and average stiffness were assessed. RESULTS: Correlation coefficients for the angular displacement on the 100th cycle were as follows: 10 N, R = 0.62, 20 N, R = 0.57, and 30N, R = 0.58. Correlation values for peak load to failure as a function of canal fit were as follows: 3.0 mm, R = 0.5, 3.5 mm, R = 0.17, and 4.5 mm, R = 0.44. The canal fill ratio that intersected the line-of-best fit at an angular deformity of 10° was 0.74. Average peak forces for 3.0-, 3.5-, and 4.5-mm screws were 79.5, 136.5, and 179.6 N, respectively. Average stiffness for each caliber was 14.8, 33.4, and 52.3 N/mm. CONCLUSIONS: Increasing screw diameter and IM fill resulted in more stable fixation, but marginal gains were seen in ratios >0.9. A minimum fill ratio of 0.74 was sufficient to withstand forces of early active motion with angular deformity <10°. CLINICAL RELEVANCE: An understanding of the relationship of IM fill ratio of metacarpal screws to fracture stability may provide a framework for clinicians to optimally size these implants.

isolateR: an R package for generating microbial libraries from Sanger sequencing data.

MOTIVATION: Sanger sequencing of taxonomic marker genes (e.g. 16S/18S/ITS/rpoB/cpn60) represents the leading method for identifying a wide range of microorganisms including bacteria, archaea, and fungi. However, the manual processing of sequence data and limitations associated with conventional BLAST searches impede the efficient generation of strain libraries essential for cataloging microbial diversity and discovering novel species. RESULTS: isolateR addresses these challenges by implementing a standardized and scalable three-step pipeline that includes: (1) automated batch processing of Sanger sequence files, (2) taxonomic classification via global alignment to type strain databases in accordance with the latest international nomenclature standards, and (3) straightforward creation of strain libraries and handling of clonal isolates, with the ability to set customizable sequence dereplication thresholds and combine data from multiple sequencing runs into a single library. The tool's user-friendly design also features interactive HTML outputs that simplify data exploration and analysis. Additionally, in silico benchmarking done on two comprehensive human gut genome catalogues (IMGG and Hadza hunter-gather populations) showcase the proficiency of isolateR in uncovering and cataloging the nuanced spectrum of microbial diversity, advocating for a more targeted and granular exploration within individual hosts to achieve the highest strain-level resolution possible when generating culture collections. AVAILABILITY AND IMPLEMENTATION: isolateR is available at: https://github.com/bdaisley/isolateR.

The untapped potential of cell culture in disentangling insect-microbial relationships.

Cell culture is a powerful technique for the investigation of molecular mechanisms fundamental to health and disease in a diverse array of organisms. Cell lines offer several advantages, namely their simplistic approach and high degree of reproducibility. One field where cell culture has proven particularly useful is the study of the microbiome, where cell culture has led to the illumination of microbial influences on host immunity, nutrition, and physiology. Thus far, researchers have focused cell culture work predominantly on humans, but the growing field of insect microbiome research stands to benefit greatly from its application. Insects constitute one of Earth's most diverse and ancient life forms and, just as with humans, possess microbiomes with great significance to their health. Insects, which play critical roles in supporting food security and ecological stability, are facing increasing threats from agricultural intensification, climate change, and pesticide use. As the microbiome is closely tied to host health, gaining a more robust understanding is of increasing importance. In this review, we assert that the cultivation and utilization of insect gut cell lines in microbiome research will bridge critical knowledge gaps essential for informing insect management practices in a world under pressure.

A new lineage nomenclature to aid genomic surveillance of dengue virus.

Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system. Here we propose adding two sub-genotypic levels of virus classification, named major and minor lineages. These lineages have high thresholds for phylogenetic distance and clade size, rendering them stable between phylogenetic studies. We present an assignment tool to show that the proposed lineages are useful for regional, national and sub-national discussions of relevant DENV diversity. Moreover, the proposed lineages are robust to classification using partial genome sequences. We provide a standardized neutral descriptor of DENV diversity with which we can identify and track lineages of potential epidemiological and/or clinical importance. Information about our lineage system, including methods to assign lineages to sequence data and propose new lineages, can be found at: dengue-lineages.org.

Anandamide is an Early Blood Biomarker of Hermansky-Pudlak Syndrome Pulmonary Fibrosis.

Hermansky-Pudlak syndrome (HPS) is a group of rare genetic disorders, with several subtypes leading to fatal adult-onset pulmonary fibrosis (PF) and no effective treatment. Circulating biomarkers detecting early PF have not been identified. We investigated whether endocannabinoids could serve as blood biomarkers of PF in HPS. We measured endocannabinoids in the serum of HPS, IPF, and healthy human subjects and in a mouse model of HPSPF. Pulmonary function tests (PFT) were correlated with endocannabinoid measurements. In a pale ear mouse model of bleomycin-induced HPSPF, serum endocannabinoid levels were measured with and without treatment with zevaquenabant (MRI-1867), a peripheral CB1R and iNOS antagonist. In three separate cohorts, circulating anandamide levels were increased in HPS-1 patients with or without PF, compared to healthy volunteers. This increase was not observed in IPF patients or in HPS-3 patients, who do not have PF. Circulating anandamide (AEA) levels were negatively correlated with PFT. Furthermore, a longitudinal study over the course of 5-14 years with HPS-1 patients indicated that circulating AEA levels begin to increase with the fibrotic lung process even at the subclinical stages of HPSPF. In pale ear mice with bleomycin-induced HpsPF, serum AEA levels were significantly increased in the earliest stages of PF and remained elevated at a later fibrotic stage. Zevaquenabant treatment reduced the increased AEA levels and attenuated progression in bleomycin-induced HpsPF. Circulating AEA may be a prognostic blood biomarker for PF in HPS-1 patients. Further studies are indicated to evaluate endocannabinoids as potential surrogate biomarkers in progressive fibrotic lung diseases.

Radial Artery Reconstruction After Iatrogenic Cannulation-Related Occlusion: A Case Report.

A 59-year-old male, with a history of angiogram via the left radial artery during the workup for multi-trauma, presented to the hand clinic with a 14-day history of progressive critical ischemia in the left thumb and index finger, along with dry gangrene of the distal index fingertip. Radial artery occlusion was confirmed on imaging. The patient underwent radial artery thrombectomy, arterial reconstruction with vein graft, and amputation of the index fingertip. Postoperatively, perfusion to the thumb and index finger was restored, resulting in the resolution of associated pain and hypersensitivity. This case demonstrates the delayed presentation of ischemia following radial artery cannulation, which was successfully managed with radial artery thrombectomy and a saphenous vein graft.

The quantification of southern corn leaf blight disease using deep UV fluorescence spectroscopy and autoencoder anomaly detection techniques.

Southern leaf blight (SLB) is a foliar disease caused by the fungus Cochliobolus heterostrophus infecting maize plants in humid, warm weather conditions. SLB causes production losses to corn producers in different regions of the world such as Latin America, Europe, India, and Africa. In this paper, we demonstrate a non-destructive method to quantify the signs of fungal infection in SLB-infected corn plants using a deep UV (DUV) fluorescence spectrometer, with a 248.6 nm excitation wavelength, to acquire the emission spectra of healthy and SLB-infected corn leaves. Fluorescence emission spectra of healthy and diseased leaves were used to train an Autoencoder (AE) anomaly detection algorithm-an unsupervised machine learning model-to quantify the phenotype associated with SLB-infected leaves. For all samples, the signature of corn leaves consisted of two prominent peaks around 450 nm and 325 nm. However, SLB-infected leaves showed a higher response at 325 nm compared to healthy leaves, which was correlated to the presence of C. heterostrophus based on disease severity ratings from Visual Scores (VS). Specifically, we observed a linear inverse relationship between the AE error and the VS (R2 = 0.94 and RMSE = 0.935). With improved hardware, this method may enable improved quantification of SLB infection versus visual scoring based on e.g., fungal spore concentration per unit area and spatial localization.

Using longitudinal qualitative research to understand the experiences of minoritized people.

This paper demonstrates how Longitudinal Qualitative Research (LQR) is an innovative method to understand the lived experiences of members of minoritized groups when temporality is a structuring element of their experiences. Most qualitative research in psychology is cross-sectional, which limits our understanding of individuals whose experiences are context-dependent and linked to the temporal norms of specific social environments. LQR is unique for allowing researchers to compare change and stability over time and reveal how social challenges and barriers impact perspective shifts and long-term decision-making. To demonstrate the usefulness of LQR as an inclusive methodology, we discuss an ongoing study of career decision-making among a diverse cohort of biomedical scientists. We have used annual interviews to follow biomedical science trainees from the beginning of their PhD into the initial stages of their careers. We present case studies of minoritized scientists to illustrate the methods for long-term engagement used to elicit sensitive and critical information during their training. We show how LQR is a viable methodology for a variety of research questions and can be accomplished using large or small sample sizes and limited resources. Our primary goal is to show how LQR is useful to understand the experiences of minoritized individuals in contexts that have historically excluded them.

Direct Nanoscale Imaging Reveals the Mechanism by Which Organic Acids Dissolve Vivianite through Proton and Ligand Effects.

The coprecipitation of iron (Fe) and phosphorus (P) in natural environments limits their bioavailability. Plant root-secreted organic acids can dissolve Fe-P precipitates, but the molecular mechanism underlying mobilizing biogenic elements from highly insoluble inorganic minerals remains poorly understood. Here, we investigated vivianite (Fe3(PO4)2·8H2O) dissolution by organic acids (oxalic acid (OA), citric acid (CA), and 2'-dehydroxymugineic acid (DMA)) at three different pH values (4.0, 6.0, and 8.0). With increasing pH, the vivianite dissolution efficiency by OA and CA was decreased while that by DMA was increased, indicating various dissolution mechanisms of different organic acids. Under acidic conditions, weak ligand OA (HC2O4- > C2O42- at pH 4.0 and C2O42- at pH 6.0) dissolved vivianite through the H+ effect to form irregular pits, but under alkaline condition (pH 8.0), the completely deprotonated OA was insufficient to dissolve vivianite. At pH 4.0, CA (H2Cit- > HCit2- > H3Cit) dissolved vivianite to form irregular pits through a proton-promoted mechanism, while at pH 6.0 (HCit2- > Cit3-) and pH 8.0 (Cit3-), CA dissolved vivianite to form near-rhombohedral pits through a ligand-promoted mechanism. At three pH values ((H0)DMA3- > (H1)DMA2- at pH 4.0, (H0)DMA3- at pH 6.0, and (H0)DMA3- and one deprotonated imino at pH 8.0), strong ligand DMA dissolved vivianite to form near-rhombohedral pits via ligand-promoted mechanisms. Raman spectroscopy showed that the deprotonated carboxyl groups (COO-) and imino groups were bound to Fe on the vivianite (010) face. The surface free energy of vivianite coated with OA decreased from 29.32 mJ m-2 to 24.23 mJ m-2 and then to 13.47 mJ m-2 with increasing pH, and that coated with CA resulted in a similar pH-dependent vivianite surface free-energy decrease while that coated with DMA increased the vivianite surface free energy from 31.92 mJ m-2 to 39.26 mJ m-2 and then to 49.93 mJ m-2. Density functional theory (DFT)-based calculations confirmed these findings. Our findings provide insight into the mechanism by which organic acids dissolved vivianite through proton and ligand effects.

Assessing phage-host population dynamics by reintroducing virulent viruses to synthetic microbiomes.

Microbiomes feature complex interactions between diverse bacteria and bacteriophages. Synthetic microbiomes offer a powerful way to study these interactions; however, a major challenge is obtaining a representative bacteriophage population during the bacterial isolation process. We demonstrate that colony isolation reliably excludes virulent viruses from sample sources with low virion-to-bacteria ratios such as feces, creating "virulent virus-free" controls. When the virulent dsDNA virome is reintroduced to a 73-strain synthetic gut microbiome in a bioreactor model of the human colon, virulent viruses target susceptible strains without significantly altering community structure or metabolism. In addition, we detected signals of prophage induction that associate with virulent predation. Overall, our findings indicate that dilution-based isolation methods generate synthetic gut microbiomes that are heavily depleted, if not devoid, of virulent viruses and that such viruses, if reintroduced, have a targeted effect on community assembly, metabolism, and prophage replication.

"I only seek treatment when I am ill": experiences of hypertension and diabetes care among adults living with HIV in urban Tanzania.

BACKGROUND: For adults living with HIV (ALHIV) and comorbidities, access to comprehensive healthcare services is crucial to achieving optimal health outcomes. This study aims to describe lived experiences, challenges, and coping strategies for accessing care for hypertension and/or diabetes (HTN/DM) in HIV care and treatment clinics (CTCs) and other healthcare settings. METHODOLOGY: We conducted a qualitative study that employed a phenomenological approach between January and April 2022 using a semi-structured interview guide in six HIV CTCs in Dar es Salaam, Tanzania. We purposively recruited 33 ALHIV with HTN (n = 16), DM (n = 10), and both (n = 7). Thematic content analysis was guided by the 5As framework of access to care. FINDINGS: The majority of the participants were females, between the ages of 54-73, and were recruited from regional referral hospitals. HIV CTCs at regional referral hospitals had more consistent provision of HTN screening services compared to those from district hospitals and health centers. Participants sought HTN/DM care at non-CTC health facilities due to the limited availability of such services at HIV CTCs. However, healthcare delivery for these conditions was perceived as unaccommodating and poorly coordinated. The need to attend multiple clinic appointments for the management of HTN/DM in addition to HIV care was perceived as frustrating, time-consuming, and financially burdensome. High costs of care and transportation, limited understanding of comorbidities, and the perceived complexity of HTN/DM care contributed to HTN/DM treatment discontinuity. As a means of coping, participants frequently monitored their own HTN/DM symptoms at home and utilized community pharmacies and dispensaries near their residences to check blood pressure and sugar levels and obtain medications. Participants expressed a preference for non-pharmaceutical approaches to comorbidity management such as lifestyle modification (preferred by young participants) and herbal therapies (preferred by older participants) because of concerns about side effects and perceived ineffectiveness of HTN/DM medications. Participants also preferred integrated care and focused patient education on multimorbidity management at HIV CTCs. CONCLUSION: Our findings highlight significant barriers to accessing HTN/DM care among ALHIV, mostly related to affordability, availability, and accessibility. Integration of NCD care into HIV CTCs, could greatly improve ALHIV health access and outcomes and align with patient preference.

DNA Barcoding Analysis of Trinidad Haemagogus Mosquitoes Reveals Evidence for Putative New Species.

Background: Haemagogus janthinomys is a primary sylvan vector of yellow fever virus and the emerging Mayaro virus. However, despite its medical importance, there is a dearth of data on the molecular taxonomy of this mosquito species. Methods: In this study, DNA barcoding analysis was performed on 64 adult female mosquitoes from Trinidad morphologically identified as Hg. janthinomys. The mitochondrial cytochrome c oxidase I (COI) gene and ribosomal DNA internal transcribed spacer 2 (ITS2) region of the mosquitoes were PCR amplified and sequenced, and molecular phylogenies inferred. Results: The BLASTN analysis showed that only 20% (n = 13/66) of COI sequences had high similarity (>99% identity) to Hg. janthinomys and the remaining sequences had low similarity (<90% identity) to reference GenBank sequences. Phylogenetic analysis of COI sequences revealed the presence of four strongly supported groups, with one distinct clade that did not align with any reference sequences. Corresponding ITS2 sequences for samples in this distinct COI group clustered into three clades. Conclusions: These molecular findings suggest the existence of a putative new Haemagogus mosquito species and underscore the need for further, more in-depth investigations into the taxonomy and classification of the Haemagogus genus.

Complete genome sequence of Parabacteroides distasonis strain GP102, isolated from the cecum of a morbid pregnant laboratory guinea pig (Cavia porcellus).

Parabacteroides distasonis is an anaerobic bacterium with ambivalent health effects. P. distasonis strain GP102 was isolated from the cecum content of a morbid pregnant laboratory guinea pig (Cavia porcellus). The genome consists of one circular 5.39-Mbp chromosome with a G + C content of 44.79%.

Chikungunya: a decade of burden in the Americas.

In the Americas, one decade following its emergence in 2013, chikungunya virus (CHIKV) continues to spread and cause epidemics across the region. To date, 3.7 million suspected and laboratory-confirmed chikungunya cases have been reported in 50 countries or territories in the Americas. Here, we outline the current status and epidemiological aspects of chikungunya in the Americas and discuss prospects for future research and public health strategies to combat CHIKV in the region.

Genome sequence of Clostridium septicum strain WW106, isolated from influent wastewater at a research center with multiple-species research animal facilities.

Clostridium septicum is an anaerobic Gram-positive rod-shaped bacterial pathogen known as a lethal causative agent of progressive gas gangrene in animals and humans. We report the 3.43-Mbp genome sequence of C. septicum strain WW106, isolated from influent wastewater at a research center with multiple-species laboratory animal facilities.

Spectrum of LYST mutations in Chediak-Higashi syndrome: a report of novel variants and a comprehensive review of the literature.

INTRODUCTION: Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterised by partial oculocutaneous albinism, a bleeding diathesis, immunological dysfunction and neurological impairment. Bi-allelic loss-of-function variants in LYST cause CHS. LYST encodes the lysosomal trafficking regulator, a highly conserved 429 kDa cytoplasmic protein with an unknown function. METHODS: To further our understanding of the pathogenesis of CHS, we conducted clinical evaluations on individuals with CHS enrolled in our natural history study. Using genomic DNA Sanger sequencing, we identified novel pathogenic LYST variants. Additionally, we performed an extensive literature review to curate reported LYST variants and classified these novel and reported variants according to the American College of Medical Genetics/Association for Molecular Pathology variant interpretation guidelines. RESULTS: Our investigation unveiled 11 novel pathogenic LYST variants in eight patients with a clinical diagnosis of CHS, substantiated by the presence of pathognomonic giant intracellular granules. From these novel variants, together with a comprehensive review of the literature, we compiled a total of 147 variants in LYST, including 61 frameshift variants (41%), 44 nonsense variants (30%), 23 missense variants (16%), 13 splice site variants or small genomic deletions for which the coding effect is unknown (9%), 5 in-frame variants (3%) and 1 start-loss variant (1%). Notably, a genotype-phenotype correlation emerged, whereby individuals harbouring at least one missense or in-frame variant generally resulted in milder disease, while those with two nonsense or frameshift variants generally had more severe disease. CONCLUSION: The identification of novel pathogenic LYST variants and improvements in variant classification will provide earlier diagnoses and improved care to individuals with CHS.

Morbidity and Mortality of Birds of Prey Admitted to Rehabilitation Centers for Barbed Wire Injuries, New Mexico, USA, 2016-2021.

Interest in the role of fences in wildlife movement and injuries is growing, especially in the western US, where many miles of barbed wire fences crisscross the landscape. However, literature is limited on the effect of barbed wire on avian populations. From 2016 to 2021, six New Mexico, USA, rehabilitation centers accepted 49 raptors injured by barbed wire. Eight species were represented; the majority were Great Horned Owls (Bubo virginianus). Other owls, buteos, and a single falcon were also affected. Most of the injured birds came from counties with low human population density. The injuries tended to be severe, and most birds died or were euthanized; 11 survived, and only eight birds were released. During the study period, barbed wire injuries accounted for over 12% of Great-horned Owl admissions to rehabilitation centers and 7% of all owl admissions. At one New Mexican wildlife rehabilitation center, raptors admitted for barbed wire-associated injuries were more likely to die or be euthanized compared with those admitted for other reasons. Given the welfare effects to these birds, more research is needed to determine whether wildlife-friendly fence modifications, such as a smooth top wire or rail, would mitigate injuries to birds of prey.

Characteristics and outcomes of hospitalized COVID-19 patients with acute kidney injury: The Makati Medical Center experience

Introduction@#Since the breakout of COVID-19 in December 2019, the virus has already affected and taken millions of lives over the past year. There is still much to learn about this disease. It has been postulated that the human kidney is a potential pathway for COVID-19 due to the presence of the ACE2 receptors found in the surfaces of kidney cells. Some studies that demonstrated acute tubular necrosis and lymphocyte infiltration among post mortem COVID-19 patients, concluding that the virus could directly damage the kidney, increasing the risk of the development of Acute Kidney Injury (AKI) among patients with COVID-19. This study investigated the incidence and severity of AKI among hospitalized COVID-19 patients and the association of the degree of AKI with regards to the severity and outcomes of COVID-19 patients.@*Methods@#This was a single-center cross-sectional study retrospective chart review of COVID-19 patients who developed AKI. Descriptive statistics were used to summarize the general and clinical characteristics of the patients. Frequency and proportion were used for categorical variables. Shapiro-Wilk test was used to determine the normality distribution of continuous variables. Continuous quantitative data that met the normality assumption was described using mean and standard deviation, while those that did not were described using median and range. Continuous variables which are normally distributed were compared using the One-way ANOVA, while those variables that are not normally distributed were compared using the Kruskal-Wallis H test. For categorical variables, the Chi-square test was used to compare the outcomes. If the expected percentages in the cells are less than 5%, Fisher's Exact Test was used instead.@*Results@#A total of 1441 COVID-19 in-patients from March 1, 2020 to March 1, 2021 were reviewed, 59 of whom were excluded. Among the adults with COVID-19 who developed AKI, 60% were in stage I, 10% in stage II, and 30% in stage III. The incidence of AKI among COVID-19 in-patients at Makati Medical Center was 13.10% (95% CI 11.36% - 14.99%). Among the 181 patients, 79 (43.65%, 95% CI 36.30 - 51.20) had died. The mortality rate is 22.02% for Stage I, 50% for Stage II, and 85.19% for Stage III. The median length of hospital stay was 12 days, ranging from 1 day up to 181 days. Full renal recovery on discharge was observed only in one-third of the patients. It was observed in 44.95% of those in Stage I, 27.78% of those in Stage II, and 5.56% of those in Stage III.@*Conclusion@#The study demonstrated that the incidence of AKI in hospitalized COVID-19 patients was 13.1% (95% CI 11.36% - 14.99%), which was lower than previously reported. This could be attributed to the longer study period wherein, to date, we have a better understanding of the disease and had already established a standard of care for treatment for the disease attributing to the decreased incidence of AKI among COVID-19 patients than what was initially reported. The development of AKI has a direct correlation with the degree of infection. Among patients who developed AKI, 20% required renal replacement therapy. Overall development of AKI increases the risk of mortality among hospitalized COVID-19 patients. The stage of AKI has a direct correlation with regards to mortality and has an indirect relationship with regards to renal recovery.