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Reduced K+ Build-Up in T-Tubules Contributes to Resistance of the Diaphragm to Myotonia
Patients with myotonia congenita suffer from slowed muscle relaxation caused by hyperexcitability. The diaphragm is only mildly affected in myotonia congenita; discovery of the mechanism underlying its resistance to myotonia could identify novel therapeutic targets. Intracellular recordings from two mouse models of myotonia congenita revealed the diaphragm had less myotonia than either the extensor digitorum longus (EDL) or the soleus muscles. A mechanism contributing to resistance of the diaphragm to myotonia was reduced depolarization of the interspike membrane potential during repetitive firing of action potentials, a process driven by build-up of K+ in small invaginations of muscle membrane known as t-tubules. We explored differences between diaphragm and EDL that might underlie reduction of K+ build-up in diaphragm t-tubules. Smaller size of diaphragm fibres, which promotes diffusion of K+ out of t-tubules, was identified as a contributor. Intracellular recording revealed slower repolarization of action potentials in diaphragm suggesting reduced Kv conductance. Higher resting membrane conductance was identified suggesting increased Kir conductance. Computer simulation found that a reduction of Kv conductance had little effect on K+ build-up whereas increased Kir conductance lessened build-up, although the effect was modest. Our data and computer simulation suggest opening of K+ channels during action potentials has little effect on K+ build-up whereas opening of K+ channels during the interspike interval slightly lessens K+ build-up. We conclude that activation of K+ channels may lessen myotonia by opposing depolarization to action potential threshold without worsening K+ build-up in t-tubules
High-Grade Liver Injuries With Contrast Extravasation Managed Initially With Interventional Radiology Versus Observation: A Secondary Analysis of a WTA Multicenter Study
Background: High-grade liver injuries with extravasation (HGLI + Extrav) are associated with morbidity/mortality. For low-grade injuries, an observation (OBS) first-strategy is beneficial over initial angiography (IR), however, it is unclear if OBS is safe for HGLI + Extrav. Therefore, we evaluated the management of HGLI + Extrav patients, hypothesizing IR patients will have decreased rates of operation and mortality. Methods: HGLI + Extrav patients managed with initial OBS or IR were included. The primary outcome was need for operation. Secondary outcomes included liver-related complications (LRCs) and mortality. Results: From 59 patients, 23 (39.0%) were managed with OBS and 36 (61.0%) with IR. 75% of IR patients underwent angioembolization, whereas 13% of OBS patients underwent any IR, all undergoing angioembolization. IR patients had an increased rate of operation (13.9% vs. 0%, p = 0.049), but no difference in LRCs (44.4% vs. 43.5%) or mortality (5.6% vs. 8.7%) versus OBS patients (both p \u3e 0.05). Conclusion: Over 60% of patients were managed with IR initially. IR patients had an increased rate of operation yet similar rates of LRCs and mortality, suggesting initial OBS reasonable in appropriately selected HGLI + Extrav patients
In-Hospital Risk Factors for Reintervention and Amputation in Brachial Arterial Trauma
Introduction: Brachial artery trauma is a rare but potentially devastating injury. There is little data regarding risk factors for reintervention and amputation prevention in this population, as well as anticoagulant (AC) and antiplatelet (AP) regimens and outcomes after discharge in trauma patients with vascular injuries requiring repair. This study aims to identify in-hospital risk factors for reintervention and amputation and stratify outcomes of follow-up by discharge AC or AP regimen. Methods: The AAST Prospective Observational Vascular Injury Trial database was queried for all patients who underwent traumatic brachial arterial repair from 2013 to 2022. Patients were evaluated by need for reintervention, amputation, and outcomes at follow-up by AC or AP regimen. Results: Three hundred and eleven patients required brachial repair, 28 (9%) required reoperation, and 8 (2.6%) required amputation. High injury severity score and an increased number of packed red blood cells and platelets showed a significant increase for reoperation and amputation. Damage control and shunt use were significant for the need to reoperate. Seventy-four percent (221/298) of patients were discharged with postoperative AC or AP regimens. There was no significant difference of short-term follow-up by type of AC or AP regimen. Conclusions: Damage control and temporary shunt may lead to additional operations but not an increase in amputations. However, anticoagulation intraoperatively and postoperatively does not appear to play a significant role in reducing reintervention. It also suggests that there is no increase in short-term follow-up complications with or without AC or AP therapy
The Implications of Poor Nutritional Status on Outcomes of Geriatric Trauma Patients
Background: Malnutrition is shown to be associated with worse outcomes among surgical patients, yet its postdischarge outcomes in trauma patients are not clear. This study aimed to evaluate both index admission and postdischarge outcomes of geriatric trauma patients who are at risk of poor nutritional status. Methods: This is a secondary analysis of the prospective observational American Association of Surgery for Trauma Frailty Multi-institutional Trial. Geriatric (≥65 years) patients presenting to 1 of the 17 Level I/II/III trauma centers (2019-2021) were included and stratified using the simplified Geriatric Nutritional Risk Index (albumin [g/dL] + body mass index [kg/m2]/10) into severe (simplified Geriatric Nutritional Risk Index \u3c5), moderate (5.5\u3e simplified Geriatric Nutritional Risk Index ≥5), mild level of nutritional risk (6\u3e simplified Geriatric Nutritional Risk Index ≥5.5), and good nutritional status (simplified Geriatric Nutritional Risk Index ≥6) and compared. Results: Of the 1,321 patients enrolled, 22% were at risk of poor nutritional status (mild: 13%, moderate: 7%, severe: 3%). The mean age was 77 ± 8 years, and the median [interquartile range] Injury Severity Score was 9 [5-13]. Patients at risk of poor nutritional status had greater rates of sepsis, pneumonia, discharge to the skilled nursing facility and rehabilitation center, index-admission mortality, and 3-month mortality (P \u3c .05). On multivariable analyses, being at risk of severe level of nutritional risk was independently associated with sepsis (adjusted odds ratio 6.21, 95% confidence interval 1.68-22.90, P = .006), pneumonia (adjusted odds ratio 4.40, 95% confidence interval 1.21-16.1, P = .025), index-admission mortality (adjusted odds ratio 3.16, 95% confidence interval 1.03-9.68, P = .044), and 3-month mortality (adjusted odds ratio 8.89, 95% confidence interval 2.01-39.43, P = .004) compared with good nutrition state. Conclusion: Nearly one quarter of geriatric trauma patients were at risk of poor nutritional status, which was identified as an independent predictor of worse index admission and 3-month postdischarge outcomes. These findings underscore the need for nutritional screening at admissio
Investigating Calcium Levels During Excitation-Contraction Coupling in Model Huntington\u27s Disease Skeletal Muscle
One of the less studied aspects of Huntington’s disease (HD) is its impact on skeletal muscle function. Recent studies have suggested that HD patients exhibit altered muscle function and reduced muscle strength, which may be related to defects in Ca2+ handling during excitation-contraction coupling (ECC). However, the underlying mechanisms of these alterations remain poorly understood. This study aims to determine if the myoplasmic Ca2+ during ECC is reduced in late-stage R6/2 (mouse model of HD) muscle fibers compared to age-matched controls during twitch or tetanic stimulation. Such a decrease would help explain weakness or fatigue in the model HD muscle. Previous work from our lab and other groups has measured a decreased rate of Ca2+ release from the sarcoplasmic reticulum (SR) during ECC. We have also shown that action potentials are prolonged in R6/2 skeletal muscle. Our previous work did not assess Ca2+ reuptake into the SR, in part because of the high concentration of EGTA, a Ca2+ chelator, equilibrated into the muscle via intracellular electrodes. Another group assessed Ca2+ release and reuptake using optical methods under a limited range of conditions with extensive modeling. For this project, we used optical methods to measure Ca2+ levels in isolated R6/2 and control muscle during various stimulation protocols in the absence of EGTA. Additionally, we quantified the amounts of key proteins involved in Ca2+ handling, including sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA), troponin C, and parvalbumin, in HD muscle cells using Western blot techniques. Overall, the objective of this study was to provide a more complete measure of muscle Ca2+ during ECC that can be used to build a predictive model of Ca2+ homeostasis in active R6/2 and control skeletal muscle. This study improves our understanding of the mechanisms underlying muscle dysfunction in HD. Ultimately, this study may lead to the development of new treatments to improve muscle function in HD patients
The Influence of Abiotic Stress and Cultivar Variation on Plant Defenses and Resistance to Emerald Ash Borer (Agrilus planipennis) in Cultivated Olive (Olea spp)
Emerald ash borer (EAB), Agrilus planipennis, is an invasive pest that significantly impacts olive trees (Olea europaea). This study aimed to assess the role of abiotic stress factors such as drought and salinity in influencing plant defenses and resistance to EAB, while also examining cultivar variation in resistance. The study specifically aimed to address: (1) What effects do varying degrees of abiotic stress (drought, salinity) have on olive trees\u27 antioxidant and peroxidase activity in olive tree? (2) Do distinct olive cultivars exhibit varying levels of resistance to EAB under various stressors? We used a controlled experimental design with two stress treatments (drought and salinity) and 20 olive cultivars to conduct the bioassay. Growth metrics (height and stem diameter), peroxidase activity, and antioxidant activity were measured, while EAB survival and performance were assessed by monitoring larval feeding and growth. Results indicated no significant differences in antioxidant activity between treatments, although low salinity slightly enhanced antioxidant responses. Peroxidase activity was highest under high salinity, and growth responses varied by treatment and cultivar, with Leccino showing the highest antioxidant activity. EAB larvae performed best under drought conditions but exhibited poor survival on certain cultivars. These findings suggest that abiotic stress influences both plant defense mechanisms and pest resistance, with cultivar-specific responses to stress and pest pressure
Evaluating Functional Inhibitors of Acid Sphingomyelinase As Potential Negative Modulators of Microvesicle Particle Release in Response to Skin Stressors
Many diseases including lupus erythematosus, atopic eczema, and rosacea can be associated with photosensitivity, which is an abnormal response to sunlight. Recent studies by our group have implicated microvesicle particles (MVP) as playing an important role in causing inflammation and systemic immunosuppression. Previous studies show that functional inhibitors of acid sphingomyelinase (FIASMA) can block MVP release in response to ultraviolet B (UVB) radiation or Platelet-activating Factor (PAF) agonist, which are skin stressors. However, more research needs to be conducted to evaluate the role of PAF, UVB and FIASMA in MVP generation and to formulate a therapeutic medication to be potentially used to treat photosensitivity. One of the major obstacles is the limited availability of human skin explants for research use. To investigate the mechanism of MVP generation and inhibition, we have proposed a preclinical model, porcine skin explants, as a substitute for human skin explants, which is comparatively easier to procure. In this study, we used one of five different FIASMA drugs imipramine, v amitriptyline, desipramine, nortriptyline, and sertraline in combination with UVB-, PAF-or phorbol ester-mediated MVP release. This study suggests that FIASMA drugs can block MVP release in response to multiple skin stressors on human HaCaT keratinocyte cells, as well as human and porcine skin explants
Trace Out the Improvement Level and Awareness of Polycyctic Ovary Syndrome (Pcos) among General People and Educational Institute of Developed and Developing Countries
One of the most prevalent hormonal problems which affect women is polycystic ovary syndrome (PCOS). It consists of several fundamentals, including reproductive, metabolic, and cardiovascular ones, and has effects on the patient\u27s health throughout the duration of their life. Limited data is available on PCOS in developing countries like Pakistan. The aim of our study is to trace out the prevalence of PCOS in developed countries like America and China as well as developing countries like Pakistan. The study was done in the above mention developed and developing countries through the interviews of people by online questionnaire. This survey research was completed in April 2023 to July 2023. 560 responses were collected during the studied duration. We have seen that the females of 24 year age have maximum effects of PCOS. According to this survey 74.4 % unmarried females are affected by PCOS. According to our finding 71.8 % affected females were reported in developing countries and 28.2 % females are reported in developed countries. Our survey also shows that irregular menstrual cycle, hair loss and hair thinning, weight gain or difficulty in weight loss, acne or oily skin, excessive hair growth are the some common symptoms of PCOS. Hormonal birth control, insulin sensitizing medication, Anti-androgen medication, fertility treatment, life style changes like diet, exercise and surgery are the some treatments that were received for PCOS by affected females. We recommended that more awareness is required in both developed and developing countries through TV, Radio, Newspapers and social media plate forms
Water Quality and Macroinvertebrates Assessment of Eniong Creek, Akwa Ibom State, Niger Delta, Nigeria
The water quality and macroinvertebrates from the downstream section of Eniong Creek were studied for six months, between August 2022 and January 2023 in three sampling stations/ points; to evaluate the ecological integrity and its suitability for habitation of aquatic organisms. Water samples were collected using sterilized plastic bottles and 250 mL reagent bottles for biochemical oxygen demand, and analyzed in accordance with the standard examination methods. Water temperature, dissolved oxygen (DO), transparency (TP), total dissolved solids (TDS), electrical conductivity (EC), and pH were measured in situ while water samples were collected for determination of phosphate (PO4-), nitrate (NO3-), sulphate (SO4-), total suspended solids (TSS), and biochemical oxygen demand (BOD5) in the laboratory. Macroinvertebrates samples were collected using the modified kick sampling technique, and identified using standard keys. The results showed that mean values for pH, DO, BOD5 in stations I, II, and PO4-, TSS in all the stations were deviated from the permissible limits. Three phyla, comprising of six classes of macroinvertebrates were recorded. Phylum Mollusca constituted the highest percentage composition (221 individuals, 87.0 %), while Annelida was the lowest (16 individuals, 6.3 %). Maximum species (115, 45.3 %) was obtained in point III while minimum (62, 24.4 %) was in point II. The study reveals that the economic activities couples with climate changes and seasonal factor influenced the concentrations of certain water parameters and macroinvertebrates assemblages. Thus, the creek should be protected by regulating the level of economic activities within the watershed, in order to improve water quality, maintaining the ecological integrity, and socio-economic services they provide
Impact of Infestation of Flour by Stored Food Pest Insects Ephestia Kuehniella on Quality Flour: Physico-Chemical Analyses
The primary reason for significant post-harvest losses globally stems from the infestation of insect pests. These beetles, as they progress through their life cycle, lead to the deterioration of stored food, capable of decimating an entire inventory within a remarkably brief timeframe. Quality control is a system that monitors product quality, assuring and detecting any spoilage of a product, the impact of infestation of flour by pairs of stored food pest insects E. kuehniella on quality flour was evaluated by physicochemical analyses over time. Provoked exposure of 200 g of flour to 5, 10, and 20 couples of Ephestia keuhniella under experimental conditions was carried out and a series of analyses allowed us to highlight the qualitative and quantitative parameters of flour have been made. These physicochemical analyses were carried out after 1, 2, and 3 months of exposure to the different number of pairs of the pest where the following parameters were evaluated: Particle size, protein level, gluten content, sedimentation index, and water contents. The results obtained showed a high deterioration of the quality of the flour which results in a highly significant decrease in the protein content and the gluten rate. Concerning the humidity and the granulometry or the outcrop rate, the results obtained reveal a significant increase compared to the controls. By the end of the exposure, the population of pests had significantly increased. Their presence reduced the quality of the products and caused direct damage to food due to chemicals produced by the mandibular glands. Notably, larvae can lower the quality of stored products by feeding on them and releasing feces. The growth of these insects and the spread of mold on stored foods can lead to changes in the quality of grains and the production of mycotoxins that are harmful to consumers\u27 health