Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

AIMS: Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems. METHODS: We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N = 346). The Timeline Follow-back was used to assess WHO risk drinking level reductions and the Pittsburgh Sleep Quality Index was used to assess sleep quality over the prior month at baseline and the end of treatment. RESULTS: Sleep problem scores in the active medication and placebo groups improved equally. Fewer sleep problems were noted among individuals who achieved at least a 1-level reduction (B = -0.99, 95% confidence interval (CI) [-1.77, -0.20], P = .014) or at least a 2-level reduction (B = -0.80, 95% CI [-1.47, -0.14], P = .018) in WHO risk drinking levels at the end of treatment. Reductions in drinking, with abstainers excluded from the analysis, also predicted fewer sleep problems at the end of treatment (1-level: B = -1.01, 95% CI [-1.83, -0.20], P = .015; 2-level: B = -0.90, 95% CI [-1.59, -0.22], P = .010). CONCLUSIONS: Drinking reductions, including those short of abstinence, are associated with improvements in sleep problems during treatment for AUD. Additional assessment of the causal relationships between harm-reduction approaches to AUD and improvements in sleep is warranted.

Subjective stress and any drinking during alcohol treatment: Disentangling within and between person autoregressive effects.

Alcohol use has been shown to increase stress, and there is some evidence that stress predicts subsequent alcohol use during treatment for alcohol use disorder (AUD), particularly among females who are more likely to report coping-motivated drinking. Gaining a better understanding of the processes by which stress and alcohol use are linked during treatment could potentially inform AUD treatment planning. The current study aimed to characterize the association between stress and drinking during the course of AUD treatment and whether there were sex differences in these associations. Secondary data analyses of the COMBINE study (N = 1375; 69% male, 76.3% non-Hispanic and white, average age of 44.4 years) were conducted to examine self-reported perceived stress and alcohol consumption across 16 weeks of treatment for AUD using a Bayesian random-intercept cross-lagged panel model. There was stronger evidence for any alcohol use predicting greater than typical stress in subsequent weeks and less strong evidence for stress increasing the subsequent probability of alcohol use, particularly among males. For females, greater stress predicted subsequent drinking earlier in the treatment period, and a lower probability of subsequent drinking in the last week of treatment. Interventions might specifically focus on targeting reductions in stress following drinking occasions.

Roux-en-Y partial volvulus in biliary-digestive reconstruction in children.

Various complications occur after a biliary-digestive reconstruction. Volvulus of a segment of the biliodigestive loop has not been described. Two patients who underwent biliodigestive bypass, years later, began with sudden and intense abdominal pain, associated with a volvulus with necrosis of a segment of this biliodigestive loop. This complication occurred many years after the initial correction, and manifested with sudden abdominal pain without impaired liver function, as occurred in these patients.

Diversas complicaciones pueden ocurrir después de una reconstrucción biliodigestiva. El vólvulo de un segmento del asa biliodigestiva no ha sido descrito. Dos pacientes operados de derivación biliodigestiva, años después iniciaron con dolor abdominal súbito e intenso, asociado a un vólvulo con necrosis de un segmento de la asa interpuesta. Se ha descrito el vólvulo de toda el asa interpuesta, pero no el de solo una pequeña porción de esta. La complicación ocurrió muchos años después de la corrección inicial y se manifiesto con dolor abdominal súbito sin deterioro de la función hepática, como sucedió en estos pacientes.

Effectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile.

In light of the ongoing COVID-19 pandemic and the emergence of new SARS-CoV-2 variants, understanding the effectiveness of various booster vaccination regimens is pivotal. In Chile, using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluate the effectiveness against COVID-19-related intensive care unit (ICU) admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series followed by a homologous booster, and CoronaVac primary series followed by an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimate the vaccine effectiveness weekly from February 14 to August 15, 2022, by determining hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot is 88.2% (95%CI, 86.2-89.9) against ICU admissions and 90.5% (95%CI 89.4-91.4) against death. Vaccine effectiveness shows a mild decrease for all regimens and outcomes, probably linked to the introduction of BA.4 and BA.5 Omicron sub-lineages and the waning of immunity. Based on our findings, individuals might not need additional boosters for at least 6 months after receiving a second mRNA booster shot in this setting.

Delayed metabolic disturbances in the myocardium after exertional heat stroke: contrasting effects of exertion and thermal load.

Epidemiological studies report higher risks of cardiovascular disease in humans exposed to heat stroke earlier in life. Previously, we explored mechanistic links between heat stroke and developing cardiac abnormalities using a preclinical mouse model of exertional heat stroke (EHS). Profound metabolic abnormalities developed in the ventricles of females but not males after 2 wk of recovery. Here we tested whether this lack of response in males could be attributed to the lower exercise performances or reduced thermal loads they experienced with the same running protocol. We systematically altered environmental temperature (Te) during EHS to manipulate heat exposure and exercise performance in the males. Three groups of adult C57BL/6 male mice were studied: "EHS-34" (Te = 34°C), "EHS-41" (Te = 41°C), and "EHS-39.5" (Te = 39.5°C). Mice ran until symptom limitation (unconsciousness), reaching max core temperature (Tc,max). After a 2-wk recovery, the mice were euthanized, and the ventricles were removed for untargeted metabolomics. Results were compared against age-matched nonexercise controls. The EHS-34 mice greatly elevated their exercise performance but reached lower Tc,max and lower thermal loads. The EHS-41 mice exhibited equivalent thermal loads, exercise times, and Tc,max compared with EHS-39.5. The ventricles from EHS-34 mice exhibited the greatest metabolic disturbances in the heart, characterized by shifts toward glucose metabolism, reductions in acylcarnitines, increased amino acid metabolites, elevations in antioxidants, altered TCA cycle flux, and increased xenobiotics. In conclusion, delayed metabolic disturbances following EHS in male myocardium appear to be greatly amplified by higher levels of exertion in the heat, even with lower thermal loads and max core temperatures.NEW & NOTEWORTHY Epidemiological data demonstrate greater cardiovascular risk in patients with previous heat stroke exposure. Using a preclinical mouse model of exertional heat stroke, male mice were exposed to one of three environmental temperatures (Te) during exercise. Paradoxically, after 2 wk, the mice in the lowest Te, exhibiting the largest exercise response and lowest heat load, had the greatest ventricular metabolic disturbances. Metabolic outcomes resemble developing left ventricular hypertrophy or stress-induced heart disease.

Impact of alternative food on predator diet in a Leslie-Gower model with prey refuge and Holling â ¡ functional response.

Since certain prey hide from predators to protect themselves within their habitats, predators are forced to change their diet due to a lack of prey for consumption, or on the contrary, subsist only with alternative food provided by the environment. Therefore, in this paper, we propose and mathematically contrast a predator-prey, where alternative food for predators is either considered or not when the prey population size is above the refuge threshold size. Since the model with no alternative food for predators has a Hopf bifurcation and a transcritical bifurcation, in addition to a stable limit cycle surrounding the unique interior equilibrium, such bifurcation cases are transferred to the model when considering alternative food for predators when the prey size is above the refuge. However, such a model has two saddle-node bifurcations and a homoclinic bifurcation, characterized by a homoclinic curve surrounding one of the three interior equilibrium points of the model.

Women's use of alcohol: Neurobiobehavioral concomitants and consequences.

In this narrative review, we draw from historical and contemporary literature to explore the impact of alcohol consumption on brain and behavior among women. We examine three domains: 1) the impact of alcohol use disorder (AUD) on neurobiobehavioral outcomes, 2) its impact on social cognition/emotion processing, and 3) alcohol's acute effects in older women. There is compelling evidence of alcohol-related compromise in neuropsychological function, neural activation, and brain structure. Investigations of social cognition and alcohol effects in older women represent emerging areas of study. Initial analyses suggest that women with AUD show significant deficits in emotion processing, a finding also observed in older women who have consumed a moderate dose of alcohol. Critically, despite the long-recognized need for programmatic interrogation of alcohol's effect in women, studies with sufficient numbers of women for meaningful analysis represent a small proportion of the literature, constraining interpretation and generalization.

Chitosomes Loaded with Docetaxel as a Promising Drug Delivery System to Laryngeal Cancer Cells: An In Vitro Cytotoxic Study.

Current delivery of chemotherapy, either intra-venous or intra-arterial, remains suboptimal for patients with head and neck tumors. The free form of chemotherapy drugs, such as docetaxel, has non-specific tissue targeting and poor solubility in blood that deters treatment efficacy. Upon reaching the tumors, these drugs can also be easily washed away by the interstitial fluids. Liposomes have been used as nanocarriers to enhance docetaxel bioavailability. However, they are affected by potential interstitial dislodging due to insufficient intratumoral permeability and retention capabilities. Here, we developed and characterized docetaxel-loaded anionic nanoliposomes coated with a layer of mucoadhesive chitosan (chitosomes) for the application of chemotherapy drug delivery. The anionic liposomes were 99.4 ± 1.5 nm in diameter with a zeta potential of -26 ± 2.0 mV. The chitosan coating increased the liposome size to 120 ± 2.2 nm and the surface charge to 24.8 ± 2.6 mV. Chitosome formation was confirmed via FTIR spectroscopy and mucoadhesive analysis with anionic mucin dispersions. Blank liposomes and chitosomes showed no cytotoxic effect on human laryngeal stromal and cancer cells. Chitosomes were also internalized into the cytoplasm of human laryngeal cancer cells, indicating effective nanocarrier delivery. A higher cytotoxicity (p < 0.05) of docetaxel-loaded chitosomes towards human laryngeal cancer cells was observed compared to human stromal cells and control treatments. No hemolytic effect was observed on human red blood cells after a 3 h exposure, proving the proposed intra-arterial administration. Our in vitro results supported the potential of docetaxel-loaded chitosomes for locoregional chemotherapy delivery to laryngeal cancer cells.

An Interactive Knowledge and Learning Environment in Smart Foodsheds.

The Internet of Food (IoF) is an emerging field in smart foodsheds, involving the creation of a knowledge graph (KG) about the environment, agriculture, food, diet, and health. However, the heterogeneity and size of the KG present challenges for downstream tasks, such as information retrieval and interactive exploration. To address those challenges, we propose an interactive knowledge and learning environment (IKLE) that integrates three programming and modeling languages to support multiple downstream tasks in the analysis pipeline. To make IKLE easier to use, we have developed algorithms to automate the generation of each language. In addition, we collaborated with domain experts to design and develop a dataflow visualization system, which embeds the automatic language generations into components and allows users to build their analysis pipeline by dragging and connecting components of interest. We have demonstrated the effectiveness of IKLE through three real-world case studies in smart foodsheds.

Ovariectomy aggravates the pathophysiological response to exertional heat stroke in mice.

Female mice have a greater capacity for exercising in the heat than male mice, reaching greater power output and longer times of heat exposure before succumbing to exertional heat stroke (EHS). Differences in body mass, size, or testosterone do not explain these distinct sex responses. Whether the ovaries could account for the superior exercise capacity in the heat in females remains unknown. Here, we determined the influence of ovariectomy (OVX) on exercise capacity in the heat, thermoregulation, intestinal damage, and heat shock response in a mouse EHS model. We performed bilateral OVX (n = 10) or sham (n = 8) surgeries in young adult (4 mo) female C57/BL6J mice. Upon recovery from surgeries, mice exercised on a forced wheel placed inside an environmental chamber set at 37.5 °C and 40% relative humidity until experiencing loss of consciousness (LOC). Terminal experiments were performed 3 h after LOC. OVX increased body mass by the time of EHS (sham = 3.8 ± 1.1, OVX = 8.3 ± 3.2 g, P < 0.05), resulted in shorter running distance (sham = 753 ± 189, OVX = 490 ± 87 m, P < 0.05), and shorter time to LOC (sham = 126.3 ± 21, OVX = 99.1 ± 19.8 min, P < 0.05). Histopathological assessment of the intestines revealed damage in the jejunum (sham = 0.2 ± 0.7, OVX = 2.1 ± 1.7 AU, P < 0.05) and ileum (sham = 0.3 ± 0.5, OVX = 1.8 ± 1.4 AU, P < 0.05). OVX increased mesenteric microvascular density (sham = 101 ± 25, OVX = 156 ± 66 10-2 mm/mm2, P < 0.05) and decreased concentration of circulatory heat shock protein 72 (HSP72) (sham = 26.7 ± 15.8, OVX = 10.3 ± 4.6 ng/mL, P < 0.05). No differences were observed in cytokines or chemokines between groups. Our findings indicate that OVX aggravates the pathophysiological response to EHS in mice.NEW & NOTEWORTHY Females outperform males in a mouse model of exertional heat stroke (EHS). Here, we show for the first time the impact of ovariectomy (OVX) on EHS pathophysiology. OVX resulted in a shorter exercise capacity in the heat, greater intestinal damage, and lower heat shock response following EHS.

Age as a potential modulator of alcohol-related deficits.

Although their individual significance is well-documented, the interaction effects of age, sex, and alcohol use disorder (AUD) have undergone little systematic investigation. Here, we extend prior work interrogating sex and group (AUD vs. community comparison [CC]) by probing the main and interaction effects of age on emotion processes as well as two conventional neuropsychological tests. Main effects for age and group were anticipated; however, interaction effects comprise our primary focus. While sex differences in AUD prevalence are commonly reported, sex differences within AUD samples are inconsistently found. Therefore, we pose our inquiry regarding sex as exploratory. In this study, 54 CC (n = 30 women) and 55 AUD (n = 14 women) subjects completed a battery that included an emotional face discrimination task, the Trail-Making Test-B (TMT-B), and the Digit Symbol Substitution Test (DSST). The initial/full models included the main and interaction effects of age (as a continuous variable; 25-59 years of age), sex, and group (AUD, CC). In analysis of the emotional face discrimination task, performance on a non-affective face discrimination task was entered as a covariate. Analysis of emotion identification revealed group and age main (p = .02; d = .53 & .003; d = .50, respectively) and interaction effects (p = .05; d = .41). The latter suggested that age and emotion processing performance were positively correlated in the AUD group, but unrelated in the CC group. Notably, neither sex, main, nor interaction effects achieved significance. Using the full model, analysis of the TMT-B and DSST failed to show sex effects or reveal expected performance decrement in the AUD group. To clarify the latter, simple models including only group as well as correlations between age and performance by group for each task were conducted. These analyses demonstrated the expected AUD-related deficits and suggested differential relationships between age and neurocognitive performance as a function of both group and task. Outcomes across tasks emphasize the need to reframe aging effects, particularly in the context of AUD.

Impact of visual field loss post-stroke on activities of daily living: a prospective cohort study.

This study investigated the ADL performances of people with VFL after an acute stroke using an observation-based evaluation of ADL skills, the Assessment of Motor and Process Skills. The AMPS was administered on initial assessment and at ≥11 weeks follow-up on 58 adults with a mild stroke, with (n = 16) and without VFL (n = 42), over a 13-month period. The AMPS guidelines on clinically relevant difference of 0.30 logits were used to determine the differences of the groups' ADL performance on initial assessment and follow-up. The study found that the ADL motor and process scores did not differ significantly on initial assessment. The study observed no clinically relevant difference between the ADL motor and process scores of between the VFL and non-VFL on initial assessment and follow-up but demonstrated clinically relevant improvements in ADL motor and process scores of both groups from initial assessment to follow-up. VFL does not have an additional negative impact on ADL performance of those with a mild stroke and does not impede improvement of ADL performance over time.

Evaluation of the discrimination and calibration of predictive scores of mortality in ECMO for patients with COVID-19.

BACKGROUND: The criteria for the selection of COVID-19 patients that could benefit most from ECMO organ support are yet to be defined. In this study, we evaluated the predictive performance of ECMO mortality predictive models in patients with COVID-19. We also performed a cost-benefit analysis depending on the mortality predicted probability. We conducted a retrospective cohort study in COVID-19 patients who received ECMO at two tertiary care hospitals between March 2020 to July 2021. MATERIALS AND METHODS: We evaluated the discrimination (C-statistic), calibration (Cox calibration), and accuracy of the prediction of death due to severe ARDS in V-V ECMO score (PRESERVE), the Respiratory Extracorporeal Membrane Oxygenation Survival Score (RESP) score, and the PREdiction of Survival on ECMO Therapy-Score (PRESET) score. In addition, we compared the RESP score with Plateau pressure instead of Peak pressure. RESULTS: We included a total of 36 patients, 29 (80%) of them male and with a median (IQR) APACHE of 10 (8-15). The PRESET score had the highest discrimination (AUROCs 0.81 [95%CI 0.67-0.94]) and calibration (calibration-in-the-large 0.5 [95%CI -1.4 to 0.3]; calibration slope 2.2 [95%CI 0.7/3.7]). The RESP score with Plateau pressure had higher discrimination than the conventional RESP score. The cost per QALY in the USA, adjusted to life expectancy, was higher than USD 100 000 in patients older than 45 years with a PRESET > 10. CONCLUSION: The PRESET score had the highest predictive performance and could help in the selection of patients that benefit most from this resource-demanding and highly invasive organ support.

TNFSF13B rs9514828 gene polymorphism and soluble B cell activating factor levels: Association with apical periodontitis.

AIM: The aim of this case-control study was to evaluate the association between the TNFSF13B rs9514828 (-871 C > T) polymorphism and soluble BAFF (sBAFF) in apical periodontitis (AP) patients. METHODOLOGY: Two hundred and sixty one healthy subjects (HS) and 158 patients with AP classified as: 46 acute apical abscess (AAA), 81 primary AP (pAP) and 31 secondary AP (sAP) patients were included. Genomic DNA (gDNA) was extracted from peripheral blood cells according to the salting out method. The TNFSF13B rs9514828 (NC_000013.11:g.108269025C > T) were identified using polymerase chain reaction (PCR) followed by restriction fragment length polymorphisms (RFLP). Serum sBAFF levels were measured by ELISA test. The chi-squared or Fisher's exact test was performed. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the risk of AP associated with the rs9514828. The Mann-Whitney U test and Kruskal-Wallis analysis were used for non-normally distributed data. Differences were considered significant with a p-value <.05. RESULTS: No differences in the genotype/allele frequencies were shown between HS and patients with AAA. However, the TT genotype (OR = 2.68, 95% CI: 1.10-6.53; p = .025) and T allele (OR = 1.46, 95% CI: 1.00-2.12; p = .045) were associated with increased risk of pAP. In contrast, the minor allele T significantly decreased the risk of sAP (OR = 0.49, 95% CI: 0.024-0.99; p = .043). sBAFF serum levels were increased in AAA and pAP compared with HS (p < .01 and p = .021, respectively). The AAA patients had higher sBAFF serum levels than pAP (p = .034) and sAP (p < .01). CONCLUSIONS: These results suggest that the TNFSF13B rs9514828 (-871 C > T) polymorphism is associated with pAP susceptibility and that BAFF is a cytokine that might be involved in acute and chronic AP. The future exploration of the rs9514828 polymorphism in other AP cohorts is recommended.

Recomendación del Comité Asesor de Vacunas y Estrategias de Inmunización (CAVEI) sobre vacunación contra viruela símica en Chile

La viruela del mono fue declarada emergencia de salud pública de importancia internacional por la Organización Mundial de la Salud el año 2022. En Chile, hasta septiembre se han confirmado sobre 450 enfermos, mayoritariamente hombres jóvenes. Este poxvirus zoonótico se transmite entre humanos por contacto estrecho; la enfermedad es autolimitada y puede ser fatal en inmunocomprometidos. La prevención mediante inmunización es importante. MVA-BN es una de las tres vacunas disponibles, de 3° generación, contiene el virus vaccinia atenuado, no replicante por lo que se puede administrar a pacientes inmunocomprometidos y mujeres embarazadas y está aprobada para viruela símica en personas > 18 años. La información disponible sobre eficacia y efectividad es limitada. El CAVEI recomienda incorporar esta vacuna para interrumpir la cadena de transmisión y reducir el riesgo de enfermedad grave, en dos dosis separadas por 28 días, por vía subcutánea, priorizando el uso post-exposición para contactos estrechos con riesgo de enfermedad grave, idealmente en los primeros 4 días y hasta 14 días post contacto de riesgo y en ausencia de síntomas. Cuando el suministro de vacunas lo permita, se recomienda prevención pre-exposición para personas con alto riesgo ocupacional o por prácticas sexuales. Esta recomendación podría modificarse según la epidemiología, el suministro de vacunas y nueva información científica.

Monkeypox was declared a public health emergency of international concern by the World Health Organization during 2022. In Chile, over 450 patients have been confirmed until September, mostly young men. This zoonotic poxvirus is transmitted from humans to humans through close contact; it is a self-limiting disease and can be fatal in people with immunodeficiency. Prevention by immunization is important. MVA-BN, one of the three vaccines available, it is a third generation vaccine, based on non-replicating modified vaccinia virus, therefore can be administered to immunocompromised patients and pregnant women and it has been approved for monkeypox in people over 18 years of age. The available information on efficacy and effectiveness is limited. The CAVEI recommends incorporating this vaccine to interrupt the chain of transmission and reduce the risk of severe disease, administered subcutaneously in two doses, 28 days apart, prioritizing post exposure use for close contacts of confirmed cases with risk of severe disease, ideally within 4 days of exposure and it can be used up to 14 days after exposure and in the absence of symptoms. When the vaccine supply allows it, its application is recommended as pre-exposure prevention for people with high-risk sexual practices or with occupational risk. This recommendation could be modified according to epidemiology, vaccines supply and new scientific information.

Neuromotor deficits and altered physiological responses to repeated exertional heat stroke exposures in mice.

Exertional heat stroke (EHS) is a life-threatening illness that can lead to negative health outcomes. Using a "severe" preclinical mouse model of EHS, we tested the hypotheses that one EHS exposure results in altered susceptibility to a subsequent EHS and reduced neuromotor performance. Female C57BL/6 mice underwent two protocols, 2 wk apart, either an EHS trial (EHS) or a sham exercise control trial (EXC). For EHS, mice ran in a forced running wheel at 37.5°C/40% relative humidity until loss of consciousness, followed by a slow cooling protocol (2 h recovery at 37.5°C). EXC mice exercised equally but in ∼22°C. Mice were randomized into three groups: 1) EXC-EXC (two consecutive EXC, n = 6, 2) EHS-EXC (EHS followed by EXC, n = 5), and 3) EHS-EHS (repeated EHS, n = 9). Mice underwent noninvasive neuromotor and behavioral tests during recovery and isolated soleus force measurements at the end of recovery. At the first EHS, mice reached average peak core temperatures (Tc,max) of 42.4°C, (46% mortality). On the second EHS, average Tc,max was reduced by ∼0.7°C (P < 0.05; mortality 18%). After the first EHS, both EHS-EX and EHS-EHS showed significant reductions in maximum strength (24 h and 1 wk post). After the second EHS, strength, horizontal rotation, hindlimb tone, suspended hindlimb splay, trunk curl, and provoked biting continued to decline in the EHS-EHS group. In conclusion, exposure to a second EHS after 2 wk leads to increased exercise times in the heat, symptom limitation at a lower Tc,max, and greater deficits in neuromotor and behavioral function during recovery.

The impact of castration on physiological responses to exertional heat stroke in mice.

INTRODUCTION: The capability of male mice to exercise in hot environments without succumbing to exertional heat stroke (EHS) is markedly blunted compared to females. Epidemiological evidence in humans and other mammals also suggests some degree of greater vulnerability to heat stroke in males compared to females. The origins of these differences are unknown, but testosterone has previously been shown to induce faster elevations in core temperature during acute, passive heat exposure. In this study, we tested the hypothesis that loss of testosterone and related sex hormones through castration would improve the performance and heat tolerance of male mice during EHS exposure. METHODS: Twenty-four male mice were randomly divided into 3 groups, untreated EHS mice (SHAM-EHS), castrated EHS mice (CAS+EHS) and naïve exercise controls (NAIVE). Exercise performance and physiological responses in the heat were monitored during EHS and early recovery. Two weeks later, blood and tissues were collected and analyzed for biomarkers of cardiac damage and testosterone. RESULTS: Core temperature in CAS+EHS rose faster to 39.5°C in the early stages of the EHS trial (P<0.0001). However, both EHS groups ran similar distances, exhibited similar peak core temperatures and achieved similar exercise times in the heat, prior to symptom limitation (unconsciousness). CAS+EHS mice had ~10.5% lower body mass at the time of EHS, but this provided no apparent advantage in performance. There was no evidence of myocardial damage in any group, and testosterone levels were undetectable in CAS+EHS after gonadectomy. CONCLUSIONS: The results of these experiments exclude the hypothesis that reduced performance of male mice during EHS trials is due to the effects of male sex hormones or intact gonads. However, the results are consistent with a role of male sex hormones or intact gonads in suppressing the early and rapid rise in core temperature during the early stages of exercise in the heat.

THE APPENDICITIS INFLAMMATORY RESPONSE SCORE FOR ACUTE APPENDICITIS: IS IT IMPORTANT FOR EARLY DIAGNOSIS?

BACKGROUND: The use of Appendicitis Inflammatory Response clinical score in patients with suspected acute appendicitis makes the diagnosis more objective and accurate. AIMS: The aim of this study was to prospectively compare two groups with suspected acute appendicitis, analyzing the number of imaging tests requested, waiting time in the emergency department, until definition of conduct, as well as the sensitivity and specificity of this diagnostic method. METHODS: This is a prospective randomized study comparing 55 patients submitted to clinical-radiological diagnosis according to the routine of the service (control group), with another 55 patients submitted to the Appendicitis Inflammatory Response score flowchart (intervention group). RESULTS: Waiting time for defining the intervention group's conduct was 1.5 h shorter than the control group (p=0.02). Computed tomography was performed in 42 patients in the control group, compared with 25 in the intervention group (p=0.001). The impact of the flowchart based on the Appendicitis Inflammatory Response score of the cases compared to the control group was the reduction of appendectomies with a normal-appearing appendix from 5 to 1 and an increase in the exclusion of appendicitis diagnoses. The use of the Appendicitis Inflammatory Response score resulted in a diagnostic specificity of 92%, compared to 29% in the control group. CONCLUSIONS: The use of the Appendicitis Inflammatory Response score reduced the waiting time for the diagnosis of acute appendicitis, decreased the number of imaging tests, and increased diagnostic specificity of the disease.

In vitro models for head and neck cancer: Current status and future perspective.

The 5-year overall survival rate remains approximately 50% for head and neck (H&N) cancer patients, even though new cancer drugs have been approved for clinical use since 2016. Cancer drug studies are now moving toward the use of three-dimensional culture models for better emulating the unique tumor microenvironment (TME) and better predicting in vivo response to cancer treatments. Distinctive TME features, such as tumor geometry, heterogenous cellularity, and hypoxic cues, notably affect tissue aggressiveness and drug resistance. However, these features have not been fully incorporated into in vitro H&N cancer models. This review paper aims to provide a scholarly assessment of the designs, contributions, and limitations of in vitro models in H&N cancer drug research. We first review the TME features of H&N cancer that are most relevant to in vitro drug evaluation. We then evaluate a selection of advanced culture models, namely, spheroids, organotypic models, and microfluidic chips, in their applications for H&N cancer drug research. Lastly, we propose future opportunities of in vitro H&N cancer research in the prospects of high-throughput drug screening and patient-specific drug evaluation.

Identification of Candidate Genes for a Major Quantitative Disease Resistance Locus From Soybean PI 427105B for Resistance to Phytophthora sojae.

Phytophthora root and stem rot is a yield-limiting soybean disease caused by the soil-borne oomycete Phytophthora sojae. Although multiple quantitative disease resistance loci (QDRL) have been identified, most explain <10% of the phenotypic variation (PV). The major QDRL explaining up to 45% of the PV were previously identified on chromosome 18 and represent a valuable source of resistance for soybean breeding programs. Resistance alleles from plant introductions 427105B and 427106 significantly increase yield in disease-prone fields and result in no significant yield difference in fields with less to no disease pressure. In this study, high-resolution mapping reduced the QDRL interval to 3.1 cm, and RNA-seq analysis of near-isogenic lines (NILs) varying at QDRL-18 pinpointed a single gene of interest which was downregulated in inoculated NILs carrying the resistant allele compared to inoculated NILs with the susceptible allele. This gene of interest putatively encodes a serine-threonine kinase (STK) related to the AtCR4 family and may be acting as a susceptibility factor, based on the specific increase of jasmonic acid concentration in inoculated NILs. This work facilitates further functional analyses and marker-assisted breeding efforts by prioritizing candidate genes and narrowing the targeted region for introgression.