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This is a retrospective study of patients treated for early-stage cervical cancer to identify pathologic risk factors associated with ovarian metastases and, therefore, to establish when ovarian preservation can be performed without increasing the risk of relapse in order to improve the quality of life in premenopausal patients. Between 1982 and 2004, 1965 patients with FIGO stage IA2–IB–IIA cervical squamous cell carcinoma and nonsquamous histology types were surgically treated; 1695 (86%) patients underwent primary radical hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection, the remaining 270 patients (14%) had their ovaries preserved. The clinical records were reviewed for all patients and clinical features at presentation, the histopathology and follow-up data were recorded. Overall, ovarian metastases were diagnosed in 16 of 1695 patients, for an incidence rate of 0.9%. Univariate analysis shows age (≤45 vs >45 years: P= 0.0079), FIGO stage (IB1–IIA ≤4 cm vs IB2–IIA >4 cm: P= 0.0133), histology (squamous vs nonsquamous, P= 0.0014), noninvolved peripheral stromal thickness (<3 vs >3 mm: P= 0.0001), lymphvascular space involvement (present vs absent, P= 0.0007), lymph node status (positive vs negative, P= 0.00009) to be statistically associated with the presence of ovarian metastases. Multivariate analysis shows only age (P= 0.0119), FIGO stage (P= 0.011), histology (P= 0.001), and unaffected peripheral stromal thickness (<3 mm: P= 0.037) to be independent risk factors for ovarian metastases. Based on the present data and on the data available in the literature, ovarian preservation could be safely performed in young patients with early-stage squamous cell carcinoma (histology as the most significant risk factor), with macroscopically normal ovaries, and with preserved peripheral unaffected cervical stroma.

Using zebrafish, the authors show that neuronal activity influences which axons are selected for myelination by promoting the growth and stability of oligodendrocyte sheaths on axons. Myelination of axons in response to activity could modulate the conduction properties of specific neural circuits, thereby contributing to brain plasticity. An essential feature of vertebrate neural development is ensheathment of axons with myelin, an insulating membrane formed by oligodendrocytes. Not all axons are myelinated, but mechanisms directing myelination of specific axons are unknown. Using zebrafish, we found that activity-dependent secretion stabilized myelin sheath formation on select axons. When VAMP2-dependent exocytosis was silenced in single axons, oligodendrocytes preferentially ensheathed neighboring axons. Nascent sheaths formed on silenced axons were shorter in length, but when activity of neighboring axons was also suppressed, inhibition of sheath growth was relieved. Using in vivo time-lapse microscopy, we found that only 25% of oligodendrocyte processes that initiated axon wrapping were stabilized during normal development and that initiation did not require activity. Instead, oligodendrocyte processes wrapping silenced axons retracted more frequently. We propose that axon selection for myelination results from excessive and indiscriminate initiation of wrapping followed by refinement that is biased by activity-dependent secretion from axons.

Background Ethyl alcohol (ethanol) consumption is ostensibly known to increase the risk of morbidity and mortality during hot weather and heatwaves. However, how alcohol independently alters physiological, perceptual, and behavioral responses to heat stress remains poorly understood. Therefore, we conducted a systematic scoping review to understand how alcohol consumption affects thermoregulatory responses to the heat. Methods We searched five databases employing the following eligibility criteria, studies must have: 1) involved the oral consumption of ethanol, 2) employed a randomized or crossover-control study design with a control trial consisting of a volume-matched, non-alcoholic beverage, 3) been conducted in healthy adult humans, 4) reported thermophysiological, perceptual, hydration status markers, and/or behavioral outcomes, 5) been published in English, 6) been conducted in air or water at temperatures of > 28°C, 7) involved passive rest or exercise, and 8) been published before October 4th, 2023. Results After removing duplicates, 7256 titles were screened, 29 papers were assessed for eligibility and 8 papers were included in the final review. Across the 8 studies, there were a total of 93 participants (93 male/0 female), the average time of heat exposure was 70 min and average alcohol dose was 0.68 g·kg 1 . There were 23 unique outcome variables analyzed from the studies. The physiological marker most influenced by alcohol was core temperature (lowered with alcohol consumption in 3/4 studies). Additionally, skin blood flow was increased with alcohol consumption in the one study that measured it. Typical markers of dehydration, such as increased urine volume (1/3 studies), mass loss (1/3 studies) and decreased plasma volume (0/2 studies) were not consistently observed in these studies, except for in the study with the highest alcohol dose. Conclusion The effect of alcohol consumption on thermoregulatory responses is understudied, and is limited by moderate doses of alcohol consumption, short durations of heat exposure, and only conducted in young-healthy males. Contrary to current heat-health advice, the available literature suggests that alcohol consumption does not seem to impair physiological responses to heat in young healthy males.

Objectives Despite the well-established benefits of exercise, pregnant women are discouraged from physical activity in hot/humid conditions to avoid hyperthermia (core temperature ( T core ) ≥ 39.0 °C). Recent epidemiological evidence also demonstrates greater risk of negative birth outcomes following heat exposure during pregnancy, possibly due to thermoregulatory impairments. We aimed to determine (1) the risk of pregnant women exceeding a T core of 39.0 °C during moderate-intensity exercise in the heat; and (2) if any thermoregulatory impairments are evident in pregnant ( P ) versus non-pregnant (NP) women. Methods Thirty participants (15 pregnant in their second trimester or third trimester) completed two separate exercise-heat exposures in a climate chamber (32 °C, 45%RH). On separate occasions, each participant cycled on a semi-recumbent cycle ergometer for 45 min at a workload representative of a moderate-intensity (1) non-weight-bearing (NON-WB), or (2) weight-bearing (WB) activity. Thermoregulatory responses were monitored throughout. Results The highest rectal temperature observed in a pregnant individual was 37.93 °C. Mean end-exercise rectal temperature did not differ between groups ( P :37.53 ± 0.22 °C, NP:37.52 ± 0.34 °C, P  = 0.954) in the WB trial, but was lower in the P group ( P :37.48 ± 0.25 °C, vs NP:37.73 ± 0.38 °C, P  = 0.041) in the NON-WB trial. Whole-body sweat loss was unaltered by pregnancy during WB ( P :266 ± 62 g, NP:264 ± 77 g; P  = 0.953) and NON-WB P:265 ± 51 g, NP:300 ± 75 g; P  = 0.145) exercise. Pregnant participants reported higher ratings of thermal sensation (felt hotter) than their non-pregnant counterparts in the WB trial ( P  = 0.002) but not in the NON-WB trial, ( P  = 0.079). Conclusion Pregnant women can perform 45 min of moderate-intensity exercise at 32 °C, 45%RH with very low apparent risk of excessive maternal hyperthermia. No thermoregulatory impairments with pregnancy were observed.

New Findings What is the central question of this study? Do measurement timing, heating modality and biological sex modulate the acute effect of heat exposure on brachial artery flow‐mediated dilatation and postocclusion reactive hyperaemia? What is the main finding and its importance? The acute effect of heat exposure on brachial artery flow‐mediated dilatation and postocclusion reactive hyperaemia is: (1) transient and short lasting; (2) different between forearm and whole‐body heating; (3) unaffected by forearm heating during whole‐body heating; and (4) not different but not always equivalent between males and females. These findings provide a useful basis for future studies to investigate the acute effect of heat exposure on vascular function. The aim of this study was to gain a better understanding of the acute effect of heat exposure on brachial artery flow‐mediated dilatation (FMD) and postocclusion reactive hyperaemia (PORH) by: characterizing the time course of changes post‐heating; comparing forearm and whole‐body heating; determining the impact of forearm heating during whole‐body heating; and comparing males and females. Twenty adults (11 males and nine females; 28 ± 6 years of age) underwent two forearm [10 min electric blanket (EB) or 30 min hot water immersion (WI)] and two whole‐body [60 min water‐perfused suit with forearm covered (WBH‐C) or uncovered (WBH‐U)] heating modalities. The FMD and PORH were measured before and after (≤5, 30, 60, 90 and 120 min) heating. The FMD increased from baseline 30 min after EB, and 30 and 90 min after WI. In contrast, FMD decreased from baseline immediately after both WBH modalities. Peak PORH increased immediately after WI and both WBH modalities. Total PORH did not differ after WI, whereas it decreased immediately after both WBH modalities. Covering the forearm during WBH did not alter acute changes in FMD or PORH. Changes in FMD and PORH did not differ statistically between males and females during each heating modality, although the observed differences could not always be considered equivalent. These results demonstrate that the acute effect of heat exposure on brachial artery FMD and PORH is: (1) transient and short lasting; (2) different between forearm heating and WBH; (3) unaffected by direct forearm heating during WBH; and (4) not different but not always equivalent between males and females.

Background: Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) patients have high relapse and mortality rates. Imaging-based decision support may improve outcomes by optimising personalised treatment, and support patient risk stratification. We propose a multifactorial prognostic model including radiomics features to improve risk stratification for advanced HNSCC, compared to TNM eighth edition, the gold standard. Patient and methods: Data of 666 retrospective- and 143 prospective-stage III-IVA/B HNSCC patients were collected. A multivariable Cox proportional-hazards model was trained to predict overall survival (OS) using diagnostic CT-based radiomics features extracted from the primary tumour. Separate analyses were performed using TNM8, tumour volume, clinical and biological variables, and combinations thereof with radiomics features. Patient risk stratification in three groups was assessed through Kaplan–Meier (KM) curves. A log-rank test was performed for significance (p-value < 0.05). The prognostic accuracy was reported through the concordance index (CI). Results: A model combining an 11-feature radiomics signature, clinical and biological variables, TNM8, and volume could significantly stratify the validation cohort into three risk groups (p < 0∙01, CI of 0.79 as validation). Conclusion: A combination of radiomics features with other predictors can predict OS very accurately for advanced HNSCC patients and improves on the current gold standard of TNM8.

During development of the central nervous system oligodendrocyte precursor cells (OPCs) give rise to both myelinating oligodendrocytes and NG2 glia, which are the most proliferative cells in the adult mammalian brain. NG2 glia retain characteristics of OPCs, and some NG2 glia produce oligodendrocytes, but many others persist throughout adulthood. Why some OPCs differentiate as oligodendrocytes during development whereas others persist as OPCs and acquire characteristics of NG2 glia is not known. Using zebrafish spinal cord as a model, we found that OPCs that differentiate rapidly as oligodendrocytes and others that remain as OPCs arise in sequential waves from distinct neural progenitors. Additionally, oligodendrocyte and persistent OPC fates are specified during a defined critical period by small differences in Shh signaling and Notch activity, which modulates Shh signaling response. Thus, our data indicate that OPCs fated to produce oligodendrocytes or remain as OPCs during development are specified as distinct cell types, raising the possibility that the myelinating potential of OPCs is set by graded Shh signaling activity.