Nuclear movement in multinucleated cells.

Nuclear movement is crucial for the development of many cell types and organisms. Nuclear movement is highly conserved, indicating its necessity for cellular function and development. In addition to mononucleated cells, there are several examples of cells in which multiple nuclei exist within a shared cytoplasm. These multinucleated cells and syncytia have important functions for development and homeostasis. Here, we review a subset of the developmental contexts in which the regulation of the movement and positioning of multiple nuclei are well understood, including pronuclear migration, the Drosophila syncytial blastoderm, the Caenorhabditis elegans hypodermis, skeletal muscle and filamentous fungi. We apply the principles learned from these models to other systems.

Emergence of Erythromycin-Resistant Invasive Group A Streptococcus, West Virginia, USA, 2020-2021.

Clindamycin and ß-lactam antibiotics have been mainstays for treating invasive group A Streptococcus (iGAS) infection, yet such regimens might be limited for strains displaying MLSB phenotypes. We investigated 76 iGAS isolates from 66 patients in West Virginia, USA, during 2020-2021. We performed emm typing using Centers for Disease Control and Prevention guidelines and assessed resistance both genotypically and phenotypically. Median patient age was 42 (range 23-86) years. We found 76% of isolates were simultaneously resistant to erythromycin and clindamycin, including all emm92 and emm11 isolates. Macrolide resistance was conferred by the plasmid-borne ermT gene in all emm92 isolates and by chromosomally encoded ermA, ermB, and a single mefA in other emm types. Macrolide-resistant iGAS isolates were typically resistant to tetracycline and aminoglycosides. Vulnerability to infection was associated with socioeconomic status. Our results show a predominance of macrolide-resistant isolates and a shift in emm type distribution compared with historical reports.

Prevalence of erythromycin-resistant emm92-type invasive group A streptococcal infections among injection drug users in West Virginia, United States, 2021-23.

BACKGROUND: Increasing incidence of invasive group A Streptococcus (iGAS) disease has been reported in Europe and the USA over the past several years. Coupled with this are observations of higher rates of resistance to erythromycin and clindamycin. OBJECTIVES: To characterize iGAS and pharyngitis isolates from West Virginia (WV), a US state outside of the national Active Bacteria Core surveillance purview, where risk factors associated with iGAS infections are prevalent. METHODS: Seventy-seven invasive group A Streptococcus isolates were collected from 67 unique patients at the J.W. Ruby Memorial Hospital Clinical Microbiology Laboratory in WV from 2021 to 2023. Invasive isolates and 20 unique pharyngitis isolates were tested for clindamycin and erythromycin susceptibility in the clinical laboratory. Patient demographic and clinical information was retrieved from patient electronic health records. Isolates were further characterized based on emm subtype and detection of MLSB resistance determinants. RESULTS: Twenty-six (39%) isolates were of a single emm92 type. All emm92 isolates were uniformly erythromycin/clindamycin resistant with inducible or constitutive MLSB resistance imparted by the plasmid-borne erm(T) gene. The majority of emm92 infections were associated with adult patients who reported IV drug use, whereas no pharyngitis infections were caused by an emm92 strain. Overall, 51 (76%) of the 67 iGAS isolates were determined to carry MLSB resistance. CONCLUSIONS: Isolates of emm92 type (clonal subtype emm92.0) were associated with iGAS infections in adult IV drug users, but not with paediatric pharyngitis, and were uniformly resistant to erythromycin and clindamycin.

Transforming entomology to adapt to global concerns: 2021 student debates.

The 2021 Student Debates of the Entomological Society of America (ESA) were held at the Annual Meeting in Denver, CO. The event was organized by the Student Debates Subcommittee (SDS) of the Student Affairs Committee (SAC). The theme of the 2021 Student Debates was "Transforming Entomology to Adapt to Global Concerns", with 3 topics. Each topic had an unbiased introduction and 2 teams. The debate topics were (i) Nonnative insect introduction is an ethical approach for counteracting proliferation and overpopulation of consumers, (ii) What is the best technology to control undesirable insect pests in urban and agricultural settings? and (iii) Compared to other solutions, like plant-based diets, insect farming is the best method to address rising human global food and nutrient supply demands. Unbiased introduction speakers and teams had approximately 6 months to prepare for their presentations.

Limb blood flow and muscle oxygenation responses during handgrip exercise above vs. below critical force.

This study compared the brachial artery blood flow (Q̇BA) and microvascular oxygen delivery responses during handgrip exercise above vs. below critical force (CF; the isometric analog of critical power). Q̇BA and microvascular oxygen delivery are important determinants of oxygen utilization and metabolite accumulation during exercise, both of which increase progressively during exercise above CF. However the Q̇BA and microvascular oxygen delivery responses above vs. below CF remain unknown. We hypothesized that Q̇BA, deoxygenated-heme (deoxy-[heme]; an estimate of microvascular fractional oxygen extraction), and total-heme concentrations (total-[heme]; an estimate of changes in microvascular hematocrit) would demonstrate physiological maximums above CF despite increases in exercise intensity. Seven men and six women performed 1) a 5-min rhythmic isometric-handgrip maximal-effort test (MET) to determine CF and 2) two constant target-force tests above (severe-intensity; S1 and S2) and two constant target-force tests below (heavy-intensity; H1 and H2) CF. CF was 189.3 ± 16.7 N (29.7 ± 1.6%MVC). At end-exercise, Q̇BA was greater for tests above CF (S1: 418 ± 147 mL/min; S2: 403 ± 137 mL/min) compared to tests below CF (H1: 287 ± 97 mL/min; H2: 340 ± 116 mL/min; all p < 0.05) but was not different between S1 and S2. Further, end-test Q̇BA during both tests above CF was not different from Q̇BA estimated at CF (392 ± 37 mL/min). At end-exercise, deoxy-[heme] was not different between tests above CF (S1: 150 ± 50 µM; S2: 155 ± 57 µM), but was greater during tests above CF compared to tests below CF (H1: 101 ± 24 µM; H2: 111 ± 21 µM; all p < 0.05). At end-exercise, total-[heme] was not different between tests above CF (S1: 404 ± 58 µM; S2: 397 ± 73 µM), but was greater during tests above CF compared to H1 (352 ± 58 µM; p < 0.01) but not H2 (371 ± 57 µM). These data suggest limb blood flow limitations exist and maximal levels of muscle microvascular oxygen delivery and extraction occur during exercise above, but not below, CF.

Discovery and biological activity of computer-assisted drug designed Akt pathway inhibitors.

The P13K/Akt pathway is a growth-regulating cellular signaling pathway that is over-activated in numerous human cancers. A novel series of Akt pathway inhibitors were identified using iterative pharmacophore modeling, energy-based calculations, and property predictions of known Akt inhibitors. Inhibitory effects on activation of Akt and growth of human neoplastic cells are reported. Results show variable inhibitory effects of three selected compounds on Akt phosphorylation at a key activation site, and on proliferation of tumorigenic cells. We identify one lead compound with potent inhibitory activity on both human carcinoma cell proliferation and Akt activation.

Assessing environmental support for better health: active living opportunity audits in rural communities in the southern United States.

OBJECTIVE: Leisure-time physical activity in the United States is lower rural areas and the South and has been linked to socioeconomic and environmental aspects of where people live. The purpose of this study is to assess the built environment and policies for physical activity in rural communities. METHODS: Eight rural communities in Alabama and Mississippi were assessed in 2011 using the Rural Active Living Assessment (RALA) street segment (SSA), town-wide (TWA), and town program and policies (PPA) assessment tools. Community Health Advisors Trained as Research Partners (CHARPS) and local staff conducted the assessments. The TWA and PPA were scored by domain and total scores. Data were analyzed using descriptive and nonparametric statistics. RESULTS: 117 segments were assessed in 22 towns in 8 counties. Built environmental barriers existed in all communities. Sidewalks were available in only 10-40% of the segments. TWA identified parks and playgrounds as the most available community feature. PPA scores indicated few policies for physical activity outside of school settings with mean scores higher in Mississippi compared to Alabama (61 vs. 49, respectively). CONCLUSIONS: Multiple components of rural communities can be successfully assessed by CHARPs using RALA tools, providing information about resources and barriers for physical activity.

Cervical collar-related pressure ulcers in trauma patients in intensive care unit.

INTRODUCTION: The application of a cervical collar (C-collar) in trauma patients can be life-saving. Previous studies, however, describe development of pressure ulcers related to C-collars. OBJECTIVE: To retrospectively compare collar-related pressure ulcers (CRPUs) occurring in trauma patients admitted to the intensive care unit wearing a C-collar before and after implementation of preventive interventions and to identify risk factors for CRPU development. METHODS: Retrospective chart review of 88 trauma patients admitted to the intensive care unit before (2006) and after (2008) implementation of preventive interventions; early C-collar removal (<24 hours) and an occipital foam ring. Data were collected in the first 14 days of admission on pressure ulcer incidence, risk factors, and preventive interventions. RESULTS: The incidence of CRPUs was 1.1%. Although risk factors were present in the sample, it was impossible to identify significant risk factors for CRPU development and explore the effect of preventive interventions. CONCLUSION: The incidence of CRPUs in this study was low. CRPUs, however, should never be accepted as an inevitable complication of cervical immobilization. To identify trauma patients at risk and to apply effective preventive interventions for CRPU development, further research is needed.

Rhetoric of research: a call for renaming the clinical research partnership.

OBJECTIVE: Research cannot advance without the voluntary participation of human participants. SUMMARY OF ARGUMENTS: Full participation of research participants is often restrained by the traditional research framework, which relegates them to a predefined participant role and allows them only quasi-scripted opportunities to contribute to research processes and outcomes. Terms commonly used to refer to research participants do not reflect their significant role or send a clear message about their value. The authors propose a shift from 'patient participant' to 'participant partner.' Recognition of the true partnership between the participant and the research team, from the consent process to the trial's end, will encourage and enable fuller participation. CONCLUSION: Changing the rhetoric of research in the labelling of research participants will require dialogue. 'Respect for persons' demands it, and the research process will be better for it.

Insights into brominated flame retardant neurotoxicity: mechanisms of hippocampal neural cell death and brain region-specific transcriptomic shifts in mice.

Brominated flame retardants (BFRs) reduce flammability in a wide range of products including electronics, carpets, and paint, but leach into the environment to result in continuous, population-level exposure. Epidemiology studies have correlated BFR exposure with neurological problems, including alterations in learning and memory. This study investigated the molecular mechanisms mediating BFR-induced cell death in hippocampal cells and clarified the impact of hexabromocyclododecane (HBCD) exposure on gene transcription in the hippocampus, dorsal striatum, and frontal cortex of male mice. Exposure of hippocampus-derived HT-22 cells to various flame retardants, including tetrabromobisphenol-A (current use), HBCD (phasing out), or 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, phased out) resulted in time, concentration, and chemical-dependent cellular and nuclear morphology alterations, alterations in cell cycle and increases in annexin V staining. All 3 BFRs increased p53 and p21 expression; however, inhibition of p53 nuclear translocation using pifthrin-α did not decrease cell death. Transcriptomic analysis upon low (10 nM) and cytotoxic (10 µM) BFR exposure indicated that HBCD and BDE-47 altered genes mediating autophagy-related pathways. Further evaluation showed that BFR exposure increased LC3-II conversion and autophagosome/autolysosome formation, and co-exposure with the autophagy inhibitor 3-methyladenine (3-MA) attenuated cytotoxicity. Transcriptomic assessment of select brain regions from subchronically HBCD-exposed male mice demonstrated alteration of genes mediating vesicular transport, with greater impact on the frontal cortex and dorsal striatum compared with the dorsal and ventral hippocampus. Immunoblot analysis demonstrated no increases in cell death or autophagy markers, but did demonstrate increases in the SNARE binding complex protein SNAP29, specifically in the dorsal hippocampus. These data demonstrate that BFRs can induce chemical-dependent autophagy in neural cells in vitro and provide evidence that BFRs induce region-specific transcriptomic and protein expression in the brain suggestive of changes in vesicular trafficking.

Cardiovascular design in fin whales: high-stiffness arteries protect against adverse pressure gradients at depth.

Fin whales have an incompliant aorta, which, we hypothesize, represents an adaptation to large, depth-induced variations in arterial transmural pressures. We hypothesize these variations arise from a limited ability of tissues to respond to rapid changes in ambient ocean pressures during a dive. We tested this hypothesis by measuring arterial mechanics experimentally and modelling arterial transmural pressures mathematically. The mechanical properties of mammalian arteries reflect the physiological loads they experience, so we examined a wide range of fin whale arteries. All arteries had abundant adventitial collagen that was usually recruited at very low stretches and inflation pressures (2-3 kPa), making arterial diameter largely independent of transmural pressure. Arteries withstood significant negative transmural pressures (-7 to -50 kPa) before collapsing. Collapse was resisted by recruitment of adventitial collagen at very low stretches. These findings are compatible with the hypothesis of depth-induced variation of arterial transmural pressure. Because transmural pressures depend on thoracic pressures, we modelled the thorax of a diving fin whale to assess the likelihood of significant variation in transmural pressures. The model predicted that deformation of the thorax body wall and diaphragm could not always equalize thoracic and ambient pressures because of asymmetrical conditions on dive descent and ascent. Redistribution of blood could partially compensate for asymmetrical conditions, but inertial and viscoelastic lag necessarily limits tissue response rates. Without pressure equilibrium, particularly when ambient pressures change rapidly, internal pressure gradients will develop and expose arteries to transient pressure fluctuations, but with minimal hemodynamic consequence due to their low compliance.

Complete genome sequence of Shigella flexneri strain P099 from the gum of an adult rhesus monkey, Macaca mulatta, with gingivitis.

Shigella flexneri was associated with gingivitis, a periodontal disease, in the rhesus monkey. We report the circularized 4.8-Mbp complete genome of Shigella flexneri strain P099 isolated from the gum of an adult rhesus monkey, Macaca mulatta, with clinical symptoms of gingivitis.

Validity of the malnutrition screening tool for older adults at high risk of hospital readmission.

Malnutrition is a serious problem in older adults, particularly for those at risk of hospital readmission. The essential step in managing malnutrition is early identification using a valid nutrition screening tool. The purpose of this study was to validate the Malnutrition Screening Tool (MST) in older adults at high risk of hospital readmission. Two RNs administered the MST to identify malnutrition risk and compared it with the comprehensive Subjective Global Assessment (SGA) to assess nutritional status for patients 65 and older who had at least one risk factor for hospital readmission. The MST demonstrates substantial sensitivity, specificity, and agreement with the SGA. These findings indicate that nursing staff can use the MST as a valid tool for routine screening and rescreening to identify patients at risk of malnutrition. Use of the MST may prevent hospital-acquired malnutrition in acute hospitalized older adults at high risk of readmission.

Retia mirabilia: Protecting the cetacean brain from locomotion-generated blood pressure pulses.

Cetaceans have massive vascular plexuses (retia mirabilia) whose function is unknown. All cerebral blood flow passes through these retia, and we hypothesize that they protect cetacean brains from locomotion-generated pulsatile blood pressures. We propose that cetaceans have evolved a pulse-transfer mechanism that minimizes pulsatility in cerebral arterial-to-venous pressure differentials without dampening the pressure pulses themselves. We tested this hypothesis using a computational model based on morphology from 11 species and found that the large arterial capacitance in the retia, coupled with the small extravascular capacitance in the cranium and vertebral canal, could protect the cerebral vasculature from 97% of systemic pulsatility. Evolution of the retial complex in cetaceans-likely linked to the development of dorsoventral fluking-offers a distinctive solution to adverse locomotion-generated vascular pulsatility.

Neuromuscular recovery from severe- and extreme-intensity exercise in men and women.

Maximal voluntary contraction force (MVC), potentiated twitch force (Qpot), and voluntary activation (%VA) recover to baseline within 90 s following extreme-intensity exercise. However, methodological limitations mask important recovery kinetics. We hypothesized reductions in MVC, Qpot, and %VA at task failure following extreme-intensity exercise would be less than following severe-intensity exercise, and Qpot and MVC following extreme-intensity exercise would show significant recovery within 120 s but remain depressed following severe-intensity exercise. Twelve subjects (6 men) completed 2 severe-intensity (40, 50% MVC) and 2 extreme-intensity (70, 80% MVC) isometric knee-extension exercise bouts to task failure (Tlim). Neuromuscular function was measured at baseline, Tlim, and through 150 s of recovery. Each intensity significantly reduced MVC and Qpot compared with baseline. MVC was greater at Tlim (p < 0.01) and at 150 s of recovery (p = 0.004) following exercise at 80% MVC compared with severe-intensity exercise. Partial recovery of MVC and Qpot were detected within 150 s following Tlim for each exercise intensity; Qpot recovered to baseline values within 150 s of recovery following exercise at 80% MVC. No differences in %VA were detected pre- to post-exercise or across recovery for any intensity. Although further analysis showed sex-specific differences in MVC and Qpot, future studies should closely examine sex-dependent responses to extreme-intensity exercise. It is clear, however, that these data reinforce that mechanisms limiting exercise tolerance during extreme-intensity exercise recover quickly. Novelty: Severe- and extreme-intensity exercise cause independent responses in fatigue accumulation and the subsequent recovery time courses. Recovery of MVC and Qpot occurs much faster following extreme-intensity exercise in both men and women.

Complete Genome Sequence of Campylobacter coli Strain P4581, a Hybrid Carrying Campylobacter jejuni Genomic Content, Isolated from Rhesus Monkey, Macaca mulatta.

Campylobacter coli is a leading bacterial cause of human gastroenteritis. We reported the circularized 1.8-Mbp complete genome of MLST type 1055 C. coli strain P4581 isolated from a rhesus monkey, Macaca mulatta, hybridizing Illumina short- and Nanopore long-reads.

Development and pilot test of a peer-support based Cardiac-Diabetes Self-Management Program: a study protocol.

BACKGROUND: People with cardiac disease and type 2 diabetes have higher hospital readmission rates (22%) compared to those without diabetes (6%). Self-management is an effective approach to achieve better health outcomes; however there is a lack of specifically designed programs for patients with these dual conditions. This project aims to extend the development and pilot test of a Cardiac-Diabetes Self-Management Program incorporating user-friendly technologies and the preparation of lay personnel to provide follow-up support. METHODS/DESIGN: A randomised controlled trial will be used to explore the feasibility and acceptability of the Cardiac-Diabetes Self-Management Program incorporating DVD case studies and trained peers to provide follow-up support by telephone and text-messaging. A total of 30 cardiac patients with type 2 diabetes will be randomised, either to the usual care group, or to the intervention group. Participants in the intervention group will received the Cardiac-Diabetes Self-Management Program in addition to their usual care. The intervention consists of three face-to-face sessions as well as telephone and text-messaging follow up. The face-to-face sessions will be provided by a trained Research Nurse, commencing in the Coronary Care Unit, and continuing after discharge by trained peers. Peers will follow up patients for up to one month after discharge using text messages and telephone support. Data collection will be conducted at baseline (Time 1) and at one month (Time 2). The primary outcomes include self-efficacy, self-care behaviour and knowledge, measured by well established reliable tools. DISCUSSION: This paper presents the study protocol of a randomised controlled trial to pilot evaluates a Cardiac-Diabetes Self-Management program, and the feasibility of incorporating peers in the follow-ups. Results of this study will provide directions for using such mode in delivering a self-management program for patients with both cardiac condition and diabetes. Furthermore, it will provide valuable information of refinement of the intervention program. TRIAL REGISTRATION NUMBER: ACTRN12611000086965.

Draft Genome Sequence of the Multidrug-Resistant Strain Stenotrophomonas maltophilia N0320, Isolated from a Commercial Nanoparticle Product.

Stenotrophomonas maltophilia is an emerging opportunistic pathogen that is frequently associated with hospital infections. We report the 4.8-Mbp draft genome sequence of the oxidase-positive S. maltophilia strain N0320, an isolate from a commercial hydroxyapatite nanoparticle product.

Complete Genome Sequence of Campylobacter fetus subsp. venerealis P4531 from a Rhesus Monkey.

Campylobacter fetus subsp. venerealis is associated with animal and human infections. We report the circularized 1.8-Mbp complete genome sequence of a multilocus sequence type 43 (MLST43) C. fetus subsp. venerealis isolate from a rhesus monkey (Macaca mulatta).

Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line.

Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.