Building a Cancer Care Clinic for Transgender and Gender Diverse Individuals.

Transgender and gender diverse (TGD) people experience disparities in cancer care, including more late-stage diagnoses, worse cancer-related outcomes, and an increased number of unaddressed and more severe symptoms related to cancer and cancer-directed therapy. This article outlines plans to address the unique needs of TGD people through a TGD-focused oncology clinic. Such a clinic could be structured by upholding the following tenets: (1) champion a supportive, gender-affirming environment that seeks to continuously improve, (2) include a transdisciplinary team of specialists who are dedicated to TGD cancer care, and (3) initiate and embrace TGD-patient-centric research on health outcomes and health care delivery.

PIK3CA mutational status in tissue and plasma as a prognostic biomarker in HR+/HER2- breast cancer.

INTRODUCTION: Hotspots (HS) mutations in the PIK3CA gene may lead to poorer oncological outcomes and endocrine resistance in advanced breast cancer (BC), but their prognostic role in early-stage disease remains controversial. The overall agreement within plasma and tissue methods has not been well explored. Our aim was to correlate tissue and plasma approaches and to analyze the prognostic impact of PIK3CA mutations (PIK3CAm) in HR+/HER2- BC. METHODS: A retrospective and unicentric analysis of PIK3CA mutational status in tissue and plasma samples by Cobas®PIK3CA Mutation Kit in patients with HR+/HER2- BC. RESULTS: We analyzed 225 samples from 161 patients with luminal BC. PIK3CA mutations were identified in 62 patients (38.5%), of which 39.6% were found in tissue and 11.8% in plasma. In advanced disease, plasma and tissue correlation rate was performed in 64 cases, with an overall agreement of 70.3%. Eighty patients were treated with CDK4/6 inhibitors + endocrine therapy. We observed a moderately worse progression-free survival (PFS) in PIK3CAm versus wild-type (WT) (24 m vs. 30 m; HR = 1.39, p = 0.26). A subanalysis was carried out based on exons 9 and 20, which showed a statistically poorer PFS in PIK3CAm exon 9 versus 20 population (9.7 m vs. 30.3 m; HR = 2.84; p = 0.024). Furthermore, detection of PIK3CAm in plasma was linked to a worse PFS vs PIK3CAm detection just in tissue (12.4 vs. 29.3; HR = 2.4; p = 0.08). CONCLUSIONS: Our findings suggest the PIK3CA evaluation in tissue as the diagnostic method of choice, however, additional investigations are required to improve the role of liquid biopsy in the PIK3CA assessment. PIK3CAm show worse outcomes in advanced luminal BC, especially in exon 9 mutation carriers, despite visceral involvement, prior exposure to endocrine therapy or detection of PIK3CAm in plasma, with an unclear prognosis in early-stage disease. Nonetheless, this should be validated in a prospective cohort study.

Quality of Life is an Independent Predictor of Mortality in Patients with Heart Failure: A Prospective Cohort Study from the Colombian Heart Failure Registry (RECOLFACA).

AIM: Patients with Heart Failure (HF) commonly have poor quality of life (QoL), secondary to the persistence and severity of HF symptoms. We aimed to evaluate the prognostic value of QoL measures on all-cause mortality in patients with HF from the Colombian registry of heart failure (RECOLFACA). METHODS AND RESULTS: We analyzed data from patients registered in RECOLFACA during 2017-2019. QoL was measured using the EuroQol-5D questionnaire (EQ-5D). From the questionnaire, two independent predictors of mortality were obtained, the visual analogue scale (VAS) and the utility score (US). Primary outcome was all-cause mortality, and secondary variables evaluated were demographic factors, comorbidities, NYHA classification, medications used and laboratory test results. To analyze survival among patients, the Kaplan-Meier method and the hierarchical Cox proportional-hazards regression model were used. This study included 2514 patients from RECOLFACA. Most patients were male (57.6%), and mean age was 67.8 years. Mean value and standard deviation (SD) of the VAS score was 78.8 ± 20.1 points, while the mean and SD of the US score was 0.81 ± 0.20. As the Kaplan-Meier curve illustrated, patients in the lower quartiles of both VAS and US scores had a significantly higher probability of mortality (log-rank test: p<0.001 for both scores). CONCLUSION: QoL, as calculated by the EQ-5D questionnaire, served as an independent predictor of mortality in patients from RECOLFACA. Further studies may be needed to evaluate whether provision of optimizing therapies and follow-up care based on patients' perceived QoL reduces short- and long-term mortality rates in this population.

Microfluid biosensor for detection of hpv in patient scraping samples: Determining E6 and E7 oncogenes.

E6 and E7 oncogenes are pivotal in the carcinogenic transformation in HPV infections and efficient diagnostic methods can ensure the detection and differentiation of HPV genotype. This study describes the development and validation of an electrochemical, label-free genosensor coupled with a microfluidic system for detecting the E6 and E7 oncogenes in cervical scraping samples. The nanostructuring employed was based on a cysteine and graphene quantum dots layer that provides functional groups, surface area, and interesting electrochemical properties. Biorecognition tests with cervical scraping samples showed differentiation in the voltammetric response. Low-risk HPV exhibited a lower biorecognition response, reflected in ΔI% values of 82.33 % ± 0.29 for HPV06 and 80.65 % ± 0.68 for HPV11 at a dilution of 1:100. Meanwhile, high-risk, HPV16 and HPV18, demonstrated ΔI% values of 96.65 % ± 1.27 and 93 % ± 0.026, respectively, at the same dilution. Therefore, the biorecognition intensity followed the order: HPV16 >HPV18 >HPV06 >HPV11. The limit of detection and the limit of quantification of E6E7 microfluidic LOC-Genosensor was 26 fM, and 79.6 fM. Consequently, the E6E7 biosensor is a valuable alternative for clinical HPV diagnosis, capable of detecting the potential for oncogenic progression even in the early stages of infection.

Evaluating the Rates of Mortality and Cardiac Catheterization Using High-Sensitivity Troponin and Conventional Troponin Assays.

Non-ST segment elevation myocardial infarction (NSTEMI) is an acute coronary syndrome event where myocardial ischemia is present, with an increase of cardiac troponins without an elevation of the ST segment. One of the fundamental measures used to diagnose or rule out acute coronary syndrome (ACS) is troponin levels in the blood. Troponin is a broad term used for the category of muscle contraction regulatory proteins and is commonly measured during ACS evaluation. Troponin I is only released by cardiac tissue, while some assay measurements will also pick up troponin released by skeletal muscle injury. This retrospective observational study was performed investigating troponin assays and how they relate to patient's outcomes. The troponin assays used in this Miami hospital where the database of patients was collected between 2018 and 2023 were troponin I (cTnI), the conventional troponin assay, and the newer high-sensitivity troponin I assay (hs-cTn). In this observational study patients who received an admitting diagnosis of NSTEMI corroborated by an independent cardiologist had their respective troponin assay levels included. Patients found to have ECG changes significant for non-ischemic pathologies, or echocardiogram findings suggestive of myocardial dysfunction not clinically correlated to an ACS were excluded from the study. A total of 75 patients were included in this study and the mean age was 75.97 ±14.72 years, with a presentation of chest pain, dyspnea and general weakness recorded in 59% (n = 45) of patients. The median time between troponin samples was 6.63 hours across both assays and hs-cTn showed a 4.99% increase in variation between samples while cTnI had a decrease of 2.53%. The study objective is to support whether there is a difference in rates of cardiac catheterization or mortality based on the type of troponin testing. There was no significant association found between, the type of troponin assay used during hospital admission, and the outcomes of catheterization and death (p > 0.009).

Primary extraskeletal osteosarcomas of the pleura: A clinicopathological, immunohistochemical, and molecular analysis of 4 cases.

Four primary extraskeletal osteosarcomas of the pleura are presented. The patients were men between the ages of 63 and 78 years (average: 70.5 years) who presented with symptoms of chest pain, cough, and shortness of breath. Diagnostic imaging showed variably calcified, pleural-based masses and/or diffuse pleural thickening, clinically mimicking mesothelioma. Thoracoscopic surgical material was obtained for histopathological diagnosis. Histological findings showed the presence of a neoplastic spindle cell proliferation composed of fusiform cells with scant cytoplasm, elongated nuclei and inconspicuous nucleoli. Mitotic activity was easily identified. Additionally, all tumors showed extensive osseous differentiation in the form of osteoid matrix production; one tumor demonstrated additional chondrosarcomatous elements and another showed focal myxoid changes. Immunohistochemical analysis revealed that the tumor cells were uniformly negative for a wide variety of antibodies, including keratin AE1/AE3, keratin 5/6, D2-40, EMA, calretinin, WT-1, BerEP4, and HEG1; BAP1 was retained in all cases. In addition, fluorescence in situ hybridization for CDKN2A (p16) was negative for homozygous deletion in all tumors. Clinical follow-up showed that one patient had died 8 months after diagnosis and one had remained alive with short post-diagnostic follow-up. The tumors herein described highlight a challenging issue in the separation of mesothelioma with heterologous elements from true osteosarcomas of pleural origin. We propose that a diagnosis of extraskeletal osteosarcoma of the pleura is rendered for tumors with malignant osseous and/or cartilaginous differentiation in which comprehensive immunohistochemical studies and FISH analysis have failed to provide support for a diagnosis of mesothelioma with heterologous elements.

Atypical Thymoma (WHO Type B3) with Prominent Microcystic and Mucoid Changes Mimicking Thymic Mucoepidermoid Carcinoma: A Clinicopathological and Immunohistochemical Study of Five Cases.

Five atypical thymomas (WHO type B3) with prominent microcystic and mucoid changes are presented. The patients were four men and one woman between the ages of 57 and 72 years. The patients presented with non-specific symptoms of cough, chest pain, and dyspnea. None of the patients had a history of myasthenia gravis. Diagnostic imaging revealed the presence of anterior mediastinal masses and surgical resection was accomplished in all patients. Macroscopically, the tumors ranged in size from 3.5 to 5.0 cm in greatest diameter; four of these were well circumscribed but unencapsuled, tan colored tumors without evidence of necrosis, hemorrhage, or gross cystic changes. One tumor had more infiltrative borders and was involving the mediastinal pleura. Microscopically, the low power view was characterized by prominent microcysts that were filled with a mucoid granular material. Higher magnification demonstrated a homogenous epithelial proliferation with mild cytologic atypia but lacking mitotic activity. Focal areas of squamoid differentiation were identified but perivascular spaces were absent. Histochemical staining confirmed mucinous material in the microcysts but no intracytoplasmic mucin. Immunohistochemical stains showed positive staining of the tumor cells with keratin AE1/AE3, keratin 5/6, p63, and p40. No terminal deoxynucleotidyl transferase+/CD3 + immature lymphocytes were identified. Clinical follow-up demonstrated that four patients have remained alive without recurrence while one patient was lost to follow-up. This report highlights histological features in atypical thymoma that may be confused with other tumors, especially thymic mucoepidermoid carcinoma. Separation of these tumors may be important for patient management and prognosis.

Comprehensive Assessment of Initial Adaptation of ESBL Positive ST131 Escherichia coli to Carbapenem Exposure.

Background: It remains unclear how high-risk Escherichia coli lineages, like sequence type (ST) 131, initially adapt to carbapenem exposure in their progression to becoming carbapenem resistant. Methods: Carbapenem mutation frequency was measured in multiple subclades of extended-spectrum ß-lactamase (ESBL) positive ST131 clinical isolates using a fluctuation assay followed by whole genome sequencing (WGS) characterization. Genomic, transcriptomic, and porin analyses of ST131 C2/ H 30Rx isolate, MB1860, under prolonged, increasing carbapenem exposure was performed using two distinct experimental evolutionary platforms to measure fast vs. slow adaptation. Results: All thirteen ESBL positive ST131 strains selected from a diverse (n=184) ST131 bacteremia cohort had detectable ertapenem (ETP) mutational frequencies with a statistically positive correlation between initial ESBL gene copy number and mutation frequency (r = 0.87, P -value <1e-5). WGS analysis of mutants showed initial response to ETP exposure resulted in significant increases in ESBL gene copy numbers or mutations in outer membrane porin (Omp) encoding genes in the absence of ESBL gene amplification with subclade specific associations. In both experimental evolutionary platforms, MB1860 responded to initial ETP exposure by increasing bla CTX-M-15 copy numbers via modular, insertion sequence 26 (IS 26 ) mediated pseudocompound transposons (PCTns). Transposase activity driven by PCTn upregulation was a conserved expression signal in both experimental evolutionary platforms. Stable mutations in Omp encoding genes were detected only after prolonged increasing carbapenem exposure consistent with clinical observations. Conclusions: ESBL gene amplification is a conserved response to initial carbapenem exposure, especially within the high-risk ST131 C2/ H 30Rx subclade. Targeting such amplification could assist with mitigating carbapenem resistance development.

Cortically-based Brain Tumors in Children: A Decision-tree Approach in the Radiology Reading Room.

Cortically-based brain tumors in children constitute a unique set of tumors with variably aggressive biological behavior. As radiologists play an integral role on the multidisciplinary medical team, a clinically useful and easy-to-follow flowchart for the differential diagnoses of these complex brain tumors is essential.This proposed algorithm tree provides the latest insights into the typical imaging characteristics and epidemiologic data that differentiate the tumor entities, taking into perspective the 2021 World Health Organization's classification and highlighting classic as well as newly identified pathologic subtypes using current molecular understanding.ABBREVIATIONS: Astroblastoma=AB) Angiocentric glioma (AG) Atypical teratoid rhabdoid tumor (ATRT) Central Nervous System tumor (CNS) CNS neuroblastoma FOXR2-activated (NB-FOXR2) Desmoplastic infantile glioma/astrocytoma (DIG/DIA) Diffuse hemispheric glioma, H3 G34-mutant (DHG) Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC) Dysembryoplastic neuroepithelial tumor (DNET) Embryonal Tumors with Multilayered Rosettes (ETMR) Ependymoma (EP) Focal cortical dysplasia (FCD) Ganglioglioma/gangliocytoma (GG) Infant-type hemispheric glioma (IHG) Intracranial pressure (ICP) Long-term epilepsy-associated tumors (LEATs) Pediatric diffuse low-grade gliomas (pLGG) MR spectroscopy (MRS) Multinodular and vacuolating neuronal tumor (MVNT) Overall survival (OS) Pediatric diffuse high-grade gliomas (pHGG).

Optimization and Tradeoff Analysis for Multiple Configurations of Bio-Energy with Carbon Capture and Storage Systems in Brazilian Sugarcane Ethanol Sector.

Bio-energy systems with carbon capture and storage (BECCS) will be essential if countries are to meet the gas emission reduction targets established in the 2015 Paris Agreement. This study seeks to carry out a thermodynamic optimization and analysis of a BECCS technology for a typical Brazilian cogeneration plant. To maximize generated net electrical energy (MWe) and carbon dioxide CO2 capture (Mt/year), this study evaluated six cogeneration systems integrated with a chemical absorption process using MEA. A key performance indicator (gCO2/kWh) was also evaluated. The set of optimal solutions shows that the single regenerator configuration (REG1) resulted in more CO2 capture (51.9% of all CO2 emissions generated by the plant), penalized by 14.9% in the electrical plant's efficiency. On the other hand, the reheated configuration with three regenerators (Reheat3) was less power-penalized (7.41%) but had a lower CO2 capture rate (36.3%). Results showed that if the CO2 capture rates would be higher than 51.9%, the cogeneration system would reach a higher specific emission (gCO2/kWh) than the cogeneration base plant without a carbon capture system, which implies that low capture rates (<51%) in the CCS system guarantee an overall net reduction in greenhouse gas emissions in sugarcane plants for power and ethanol production.

Persistence of Daptomycin-Resistant and Vancomycin-Resistant Enterococci in Hospitalized Patients with Underlying Malignancies: A 7-Year Follow-Up Study.

Vancomycin-resistant enterococci (VRE) commonly colonize the gut of individuals with hematologic malignancies or undergoing hematopoietic cell transplant (HCT) and may cause bacteremia. In 2012, we identified VRE isolates from patients and patients' rooms and showed transmission networks of highly genetically related daptomycin-resistant (DR)-VRE strains. This is a follow-up study performing whole-genome sequencing (WGS) and phylogenetic analyses on 82 clinical VRE strains isolated from stools and blood cultures of patients with leukemia and HCT between 2015 and 2019. Here, we observed transmission of highly genetically related strains between rooms on the same or on different floors, including a DR-VRE strain identified in 2012. Eleven of twenty-eight patients with DR-VRE were never exposed to daptomycin, suggesting horizontal transmission. Fifteen of the twenty-eight patients with DR-VRE died within 30 days of positive blood cultures. Amongst those, one DR-VRE strain belonging to ST1471 had the virulence gene bopD responsible for biofilm formation. Additionally, to our knowledge, this is the first report of a DR-VRE strain belonging to ST323 in the United States. In summary, our study demonstrated the emergence and persistence of VRE strains, especially DR-VRE, in our hospital. Adding WGS to routine infection control measures may timely identify potential horizontal VRE transmission including multi-drug-resistant isolates.

Postmortem Sampling in Piglet Populations: Unveiling Specimens Accuracy for Porcine Reproductive and Respiratory Syndrome Detection.

Specimens collected from dead pigs are a welfare-friendly and cost-effective active surveillance. This study aimed to evaluate the accuracy of different postmortem specimens from dead piglets for disease detection, using PRRSV as an example. Three farrow-to-wean farms undergoing PRRSV elimination were conveniently selected. Samples were collected at approximately 8- and 20-weeks post-outbreak. Postmortem specimens included nasal (NS), oral (OS), and rectal (RS) swabs, tongue-tip fluids (TTF), superficial inguinal lymph nodes (SIL), and intracardiac blood. These were tested individually for PRRSV by RT-PCR. Sensitivity, specificity, negative and positive predictive values, and agreement of postmortem specimens were calculated using intracardiac sera as the gold standard. OS and SIL had the best overall performance, with sensitivities of 94.6-100%, specificities of 83.9-85.1%, and negative predictive values of 97.3-100%. TTF had high sensitivity (92.2%) but low specificity (53.9%) and positive predictive value (48.3%). While challenges in meeting sampling targets due to variable pre-weaning mortality were noted, PRRS was detected in all postmortem specimens. OS and NS showed promising results for disease monitoring, though TTF, despite their sensitivity, had lower specificity, making them less suitable for individual infection assessment but useful for assessing environmental contamination.

Field-evolved resistance to neonicotinoids in the mosquito, Anopheles gambiae, is associated with downregulation and mutations of nicotinic acetylcholine receptor subunits combined with cytochrome P450-mediated detoxification.

Neonicotinoid insecticides act selectively on their nicotinic receptor targets leading to variable sensitivity among arthropods. This study aimed to investigate the molecular mechanisms underlying contrasting susceptibility to neonicotinoids observed in wild populations of two mosquito sibling species. Bioassays and a synergism test revealed that the sister taxa, Anopheles gambiae and An. coluzzii, from Yaounde, Cameroon, rely on cytochrome P450s to detoxify neonicotinoids and develop resistance. However, contrary to An. coluzzii, An. gambiae populations are evolving stronger resistance to several active ingredients facilitated by mutations and reduced expression of nicotinic acetylcholine receptors. Six mutations were detected in coding sequences of the ß1 and α6 subunits, including two substitutions in one of the loops that modulate ligand binding and sensitivity. Allele frequencies were strongly correlated with a susceptibility gradient between An. coluzzii and An. gambiae suggesting that the mutations may play a key role in sensitivity. Messenger RNA expression levels of the ß1, α3, and α7 subunits decreased dramatically, on average by 23.27, 17.50, 15.80-fold, respectively, in wild An. gambiae populations compared to a susceptible insectary colony. By contrast, only the ß2 and α9-1 subunits were moderately downregulated (5.28 and 2.67-fold change, respectively) in field-collected An. coluzzii adults relative to susceptible colonized mosquitoes. Our findings provide critical information for the application and resistance management of neonicotinoids in malaria prevention.

Well Plate-Based Localized Electroporation Workflow for Rapid Optimization of Intracellular Delivery.

Efficient and nontoxic delivery of foreign cargo into cells is a critical step in many biological studies and cell engineering workflows with applications in areas such as biomanufacturing and cell-based therapeutics. However, effective molecular delivery into cells involves optimizing several experimental parameters. In the case of electroporation-based intracellular delivery, there is a need to optimize parameters like pulse voltage, duration, buffer type, and cargo concentration for each unique application. Here, we present the protocol for fabricating and utilizing a high-throughput multi-well localized electroporation device (LEPD) assisted by deep learning-based image analysis to enable rapid optimization of experimental parameters for efficient and nontoxic molecular delivery into cells. The LEPD and the optimization workflow presented herein are relevant to both adherent and suspended cell types and different molecular cargo (DNA, RNA, and proteins). The workflow enables multiplexed combinatorial experiments and can be adapted to cell engineering applications requiring in vitro delivery. Key features • A high-throughput multi-well localized electroporation device (LEPD) that can be optimized for both adherent and suspended cell types. • Allows for multiplexed experiments combined with tailored pulse voltage, duration, buffer type, and cargo concentration. • Compatible with various molecular cargoes, including DNA, RNA, and proteins, enhancing its versatility for cell engineering applications. • Integration with deep learning-based image analysis enables rapid optimization of experimental parameters.

Insertion and Anchoring of HIV-1 Fusion Peptide into Complex Membrane Mimicking Human T-cell.

A fundamental understanding of how HIV-1 envelope (Env) protein facilitates fusion is still lacking. The HIV-1 fusion peptide, consisting of 15 to 22 residues, is the N-terminus of the gp41 subunit of the Env protein. Further, this peptide, a promising vaccine candidate, initiates viral entry into target cells by inserting and anchoring into human immune cells. The influence of membrane lipid reorganization and the conformational changes of the fusion peptide during the membrane insertion and anchoring processes, which can significantly affect HIV-1 cell entry, remains largely unexplored due to the limitations of experimental measurements. In this work, we investigate the insertion of the fusion peptide into an immune cell membrane mimic through multiscale molecular dynamics simulations. We mimic the native T-cell by constructing a 9-lipid asymmetric membrane, along with geometrical restraints accounting for insertion in the context of gp41. To account for the slow timescale of lipid mixing while enabling conformational changes, we implement a protocol to go back and forth between atomistic and coarse-grained simulations. Our study provides a molecular understanding of the interactions between the HIV-1 fusion peptide and the T-cell membrane, highlighting the importance of conformational flexibility of fusion peptides and local lipid reorganization in stabilizing the anchoring of gp41 into the targeted host membrane during the early events of HIV-1 cell entry. Importantly, we identify a motif within the fusion peptide critical for fusion that can be further manipulated in future immunological studies.

Regulated induced proximity targeting chimeras-RIPTACs-A heterobifunctional small molecule strategy for cancer selective therapies.

We describe a protein proximity inducing therapeutic modality called Regulated Induced Proximity Targeting Chimeras or RIPTACs: heterobifunctional small molecules that elicit a stable ternary complex between a target protein (TP) selectively expressed in tumor cells and a pan-expressed protein essential for cell survival. The resulting co-operative protein-protein interaction (PPI) abrogates the function of the essential protein, thus leading to death selectively in cells expressing the TP. This approach leverages differentially expressed intracellular proteins as novel cancer targets, with the advantage of not requiring the target to be a disease driver. In this chemical biology study, we design RIPTACs that incorporate a ligand against a model TP connected via a linker to effector ligands such as JQ1 (BRD4) or BI2536 (PLK1) or CDK inhibitors such as TMX3013 or dinaciclib. RIPTACs accumulate selectively in cells expressing the HaloTag-FKBP target, form co-operative intracellular ternary complexes, and induce an anti-proliferative response in target-expressing cells.

Cadence matters: Influence of cadence on spinal load during running.

BACKGROUND: Running exposes the body to physiological and mechanical stresses that generate musculoskeletal injuries, such as low back pain due to large spinal loading. Increasing running cadence may reduce impact forces and spinal shrinkage. RESEARCH QUESTION: This study aimed to determine the relationship between spinal loading and running cadence. METHODS: This cross-sectional study included 15 runners from the local community (36 ± 11 years; 23 ± 2 kg.m-2, and 8 ± 9 years of running experience) who ran for 30 min (R30) and 60 min (R60) at a constant speed (10 km.h-1). The spinal loading was assessed via fine stature variation measurements before the run (baseline) at R30 and R60. Cadence was monitored via a wristwatch. The cadence ranged from 150 to 180 steps.min-1. A t-test was used to compare stature loss between R30 and R60 (relative to baseline), and a stepwise linear regression equation was used to identify the relationship between cadence and stature variation in each instant. RESULTS: There was a stature loss throughout the race (R30 = 5.27 ± 1.92 mm and R60 =7.51 ± 2.51 mm). A linear regression analysis revealed a negative relationship between stature loss and cadence, indicating that running at a faster cadence produces smaller spinal loading than running at slower cadences after R60 (R2 = 0.38; p<0.05). SIGNIFICANCE: Increasing running cadence might cause less spinal loading than running with a slower cadence, which may reduce the risk of injury and back disorders in runners.

Influence of membrane on the antigen presentation of the HIV-1 envelope membrane proximal external region (MPER).

The membrane proximal external region (MPER) of the HIV envelope glycoproteins has generated renewed interest after a recent phase I vaccine trial that presented MPER lipid-peptide epitopes demonstrated promise to elicit a broad neutralization response. The antigenicity of MPER is intimately associated with the membrane, and its presentation relies significantly on the lipid composition. This review brings together recent findings on the influence of membranes on the conformation of MPER and its recognition by broadly neutralizing antibodies. Specifically, the review highlights the importance of properly accounting for the balance between protein-protein and membrane-protein interactions in vaccine design.

Risk factors associated with piglet pre-weaning mortality in a Midwestern U.S. swine production system from 2020 to 2022.

Piglet pre-weaning mortality (PWM) is a significant issue in the U.S. swine industry, causing economic losses and raising sustainability and animal welfare concerns. This study conducted a multivariable analysis to identify factors associated with PWM in a Midwestern U.S. swine production system. Weekly data from 47 sow farms (7207 weaning weeks) were captured from January 2020 to December 2022. Initially, 29 variables regarding farm infrastructure, productivity parameters, health status, and interventions were selected for univariate analysis to assess their association with PWM. The initial multivariable analysis included the variables with P < 0.20 in the univariate analyses. A backward stepwise model selection was conducted by excluding variables with P > 0.05, and the final multivariable model consisted of 19 significant risk factors and 6 interaction terms. The overall average PWM for the study population was 14.02 %. Yearly variations in PWM were observed, with the highest recorded in 2020 (16.61 %) and the lowest in 2021 (15.78 %). Cohorts with a pond water source, lower farrowing rate (71.9 %), higher farrowing parity (5.1), shorter gestation length (116.2 days), and using oxytocin during farrowing had increased PWM. The higher productivity parameters such as mummies rate, stillborn rate, and average total born, the higher the PWM was. Additionally, health status and intervention-related factors were associated with PWM, where higher PWM rates were observed in herds facing porcine reproductive and respiratory syndrome virus (PRRSV) outbreaks, porcine epidemic diarrhea virus (PEDV) positive, the weeks before and during feed medication, and weeks without using Rotavirus vaccine or Rotavirus feedback. Altogether, these results corroborate that PWM is a multifactorial problem, and a better understanding of the risk factors is essential in developing strategies to improve survival rates. Therefore, this study identified the major risk factors associated with PWM for groups of pigs raised under field conditions, and the results underscore the significance of data analysis in comprehending the unique challenges and opportunities inherent to each system.