Life histories are not just fast or slow.

Life history strategies, which combine schedules of survival, development, and reproduction, shape how natural selection acts on species' heritable traits and organismal fitness. Comparative analyses have historically ranked life histories along a fast-slow continuum, describing a negative association between time allocation to reproduction and development versus survival. However, higher-quality, more representative data and analyses have revealed that life history variation cannot be fully accounted for by this single continuum. Moreover, studies often do not test predictions from existing theories and instead operate as exploratory exercises. To move forward, we offer three recommendations for future investigations: standardizing life history traits, overcoming taxonomic siloes, and using theory to move from describing to understanding life history variation across the Tree of Life.

Taxonomic revision of the Southeast Asian brook barb genus Poropuntius Smith, 1931 (Teleostei, Cyprinidae) with description of a new species from Vietnam.

Molecular data from samples encompassing 22 nominal species of Poropuntius indicate that the species-level diversity in the genus has been vastly overestimated, likely due to inadequate taxon and geographic sampling and reliance on morphological characters that vary intra-specifically. The latter includes discrete mouth morphologies related to alternate feeding strategies (ecomorphs) within populations. One new species is described, Poropuntiusanlaoensis Hoàng, Pham & Tran, sp. nov., and 17 synonyms of six valid species names of Poropuntius, P.krempfi, P.alloiopleurus, P.huangchuchieni, P.laoensis, P.kontumensis, and P.deauratus, are recognised. Additional taxonomic changes in this widespread and generally poorly known genus are likely as more molecular and morphological data become available.

Hormonal Contraception and Menstrual Cycle Control at High Altitude: A Scoping Review-UIAA Medical Commission Recommendations.

Horakova, Lenka , Susi Kriemler, Vladimír Student, Jacqueline Pichler Hefti, David Hillebrandt, Dominique Jean, Kaste Mateikaite-Pipiriene, Peter Paal, Alison Rosier, Marija Andjelkovic, Beth Beidlemann, Mia Derstine, and Linda E. Keyes. Hormonal contraception and menstrual cycle control at high altitude: a scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 00:00-00, 2024. Background: Women who use hormonal contraception (HC) may have questions about their use during travel to high altitude. This scoping review summarizes current evidence on the efficacy and safety of HC and cycle control during high-altitude travel. Methods: We performed a scoping review for the International Climbing and Mountaineering Federation (UIAA) Medical Commission series on Women's Health in the Mountains. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including contraception) with additional publications found by hand search. Results: We identified 17 studies from 7,165 potentially eligible articles. No articles assessed the efficacy of contraception during a short-term high-altitude sojourn. Current data show no advantage or disadvantage in HC users for acclimatization or acute mountain sickness (AMS). Use of HC during high-altitude travel is common and safe for menses suppression. A potential concern of estrogen-containing HC is the increased thrombotic risk, which theoretically could be compounded in hypobaric hypoxia. Conclusions: Evidence is limited for the interaction of HC and high altitude on performance, thrombosis, and contraceptive efficacy. HC does not affect the risk of AMS. The most efficacious and safest method at high altitude is generally the one women are most familiar with and already using.

Absorptive nature of scattering coefficients in stress-energy tensor formalism for room acoustics.

In the stress-energy tensor formalism, the symmetry between absorption and scattering coefficients, as proven by measurements combined with simulations, is counterintuitive. By introducing the wall admittance, we show that the scattering coefficient is partly created by the real part of the wall admittance combined with the active intensity, that is, is partly due to absorption. However, for curved surfaces or finite source distances, it also depends on the imaginary part of the wall admittance in combination with the reactive intensity, which confers its genuine scattering properties inversely proportional to the distances to the sources. Thus, for plane waves impinging on plane boundaries, or purely real admittances, scattering reduces to absorption.

Relationship between neuroimaging and cognition in frontotemporal dementia: An FDG-PET and structural MRI study.

BACKGROUND AND PURPOSE: Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative condition with a prevalence comparable to Alzheimer's disease for patients under 65 years of age. Limited studies have examined the association between cognition and neuroimaging in FTD using different imaging modalities. METHODS: We examined the association of cognition using Montreal Cognitive Assessment (MoCA) with both gray matter (GM) volume and glucose metabolism using magnetic resonance imaging and fluorodeoxyglucose (FDG)-PET in 21 patients diagnosed with FTD. Standardized uptake value ratio (SUVR) using the brainstem as a reference region was the primary outcome measure for FDG-PET. Partial volume correction was applied to PET data to account for disease-related atrophy. RESULTS: Significant positive associations were found between whole-cortex GM volume and MoCA scores (r = 0.46, p = .04). The association between whole-cortex FDG SUVR and MoCA scores was not significant (r = 0.37, p = .09). GM volumes of the frontal cortex (r = 0.54, p = .01), caudate (r = 0.62, p<.01), and insula (r = 0.57, p<.01) were also significantly correlated with MoCA, as were SUVR values of the insula (r = 0.51, p = .02), thalamus (r = 0.48, p = .03), and posterior cingulate cortex (PCC) (r = 0.47, p = .03). CONCLUSIONS: Whole-cortex atrophy is associated with cognitive dysfunction, and this association is larger than for whole-cortex hypometabolism as measured with FDG-PET. At the regional level, focal atrophy and/or hypometabolism in the frontal cortex, insula, PCC, thalamus, and caudate seem to be important for the decline of cognitive function in FTD. Furthermore, these results highlight how functional and structural changes may not overlap and might contribute to cognitive dysfunction in FTD in different ways.

Population-based deep image prior for dynamic PET denoising: A data-driven approach to improve parametric quantification.

The high noise level of dynamic Positron Emission Tomography (PET) images degrades the quality of parametric images. In this study, we aim to improve the quality and quantitative accuracy of Ki images by utilizing deep learning techniques to reduce the noise in dynamic PET images. We propose a novel denoising technique, Population-based Deep Image Prior (PDIP), which integrates population-based prior information into the optimization process of Deep Image Prior (DIP). Specifically, the population-based prior image is generated from a supervised denoising model that is trained on a prompts-matched static PET dataset comprising 100 clinical studies. The 3D U-Net architecture is employed for both the supervised model and the following DIP optimization process. We evaluated the efficacy of PDIP for noise reduction in 25%-count and 100%-count dynamic PET images from 23 patients by comparing with two other baseline techniques: the Prompts-matched Supervised model (PS) and a conditional DIP (CDIP) model that employs the mean static PET image as the prior. Both the PS and CDIP models show effective noise reduction but result in smoothing and removal of small lesions. In addition, the utilization of a single static image as the prior in the CDIP model also introduces a similar tracer distribution to the denoised dynamic frames, leading to lower Ki in general as well as incorrect Ki in the descending aorta. By contrast, as the proposed PDIP model utilizes intrinsic image features from the dynamic dataset and a large clinical static dataset, it not only achieves comparable noise reduction as the supervised and CDIP models but also improves lesion Ki predictions.

First-in-Human Study of 18F-SynVesT-2: An SV2A PET Imaging Probe with Fast Brain Kinetics and High Specific Binding.

PET imaging of synaptic vesicle glycoprotein 2A allows for noninvasive quantification of synapses. This first-in-human study aimed to evaluate the kinetics, test-retest reproducibility, and extent of specific binding of a recently developed synaptic vesicle glycoprotein 2A PET ligand, (R)-4-(3-(18F-fluoro)phenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidine-2-one (18F-SynVesT-2), with fast brain kinetics. Methods: Nine healthy volunteers participated in this study and were scanned on a High Resolution Research Tomograph scanner with 18F-SynVesT-2. Five volunteers were scanned twice on 2 different days. Five volunteers were rescanned with preinjected levetiracetam (20 mg/kg, intravenously). Arterial blood was collected to calculate the plasma free fraction and generate the arterial input function. Individual MR images were coregistered to a brain atlas to define regions of interest for generating time-activity curves, which were fitted with 1- and 2-tissue-compartment (1TC and 2TC) models to derive the regional distribution volume (V T). The regional nondisplaceable binding potential (BP ND) was calculated from 1TC V T, using the centrum semiovale (CS) as the reference region. Results: 18F-SynVesT-2 was synthesized with high molar activity (187 ± 69 MBq/nmol, n = 19). The parent fraction of 18F-SynVesT-2 in plasma was 28% ± 8% at 30 min after injection, and the plasma free fraction was high (0.29 ± 0.04). 18F-SynVesT-2 entered the brain quickly, with an SUVpeak of 8 within 10 min after injection. Regional time-activity curves fitted well with both the 1TC and the 2TC models; however, V T was estimated more reliably using the 1TC model. The 1TC V T ranged from 1.9 ± 0.2 mL/cm3 in CS to 7.6 ± 0.8 mL/cm3 in the putamen, with low absolute test-retest variability (6.0% ± 3.6%). Regional BP ND ranged from 1.76 ± 0.21 in the hippocampus to 3.06 ± 0.29 in the putamen. A 20-min scan was sufficient to provide reliable V T and BP ND Conclusion: 18F-SynVesT-2 has fast kinetics, high specific uptake, and low nonspecific uptake in the brain. Consistent with the nonhuman primate results, the kinetics of 18F-SynVesT-2 is faster than the kinetics of 11C-UCB-J and 18F-SynVesT-1 in the human brain and enables a shorter dynamic scan to derive physiologic information on cerebral blood flow and synapse density.

Relationship between Neuroimaging and Cognition in Frontotemporal Dementia: A [18 F]FDG PET and Structural MRI Study.

Background: Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous condition with a prevalence comparable to Alzheimer's Disease for patients under sixty-five years of age. Gray matter (GM) atrophy and glucose hypometabolism are important biomarkers for the diagnosis and evaluation of disease progression in FTD. However, limited studies have systematically examined the association between cognition and neuroimaging in FTD using different imaging modalities in the same patient group. Methods: We examined the association of cognition using Montreal Cognitive Assessment (MoCA) with both GM volume and glucose metabolism using structural magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography scanning ([18F]FDG PET) in 21 patients diagnosed with FTD. Standardized uptake value ratio (SUVR) using the brainstem as a reference region was the primary outcome measure for [18F]FDG PET. Partial volume correction was applied to PET data to account for disease-related atrophy. Results: Significant positive associations were found between whole-cortex GM volume and MoCA scores (r = 0.461, p = 0.035). The association between whole-cortex [18F]FDG SUVR and MoCA scores was not Significant (r = 0.374, p = 0.094). GM volumes of the frontal cortex (r = 0.540, p = 0.011), caudate (r = 0.616, p = 0.002), and insula (r = 0.568, p = 0.007) were also Significantly correlated with MoCA, as were SUVR values of the insula (r = 0.508, p = 0.018), thalamus (r = 0.478, p = 0.028), and posterior cingulate cortex (PCC) (r = 0.472, p = 0.030). Discussion: Whole-cortex atrophy is associated with cognitive dysfunction, and this effect is larger than for cortical hypometabolism as measured with [18F]FDG PET. At the regional level, focal atrophy and/or hypometabolism in the frontal lobe, insula, PCC, thalamus, and caudate seem to imply the importance of these regions for the decline of cognitive function in FTD. Furthermore, these results highlight how functional and structural changes may not overlap and might contribute to cognitive dysfunction in FTD in different ways. Our findings provide insight into the relationships between structural, metabolic, and cognitive changes due to FTD.

Synaptic loss and its association with symptom severity in Parkinson's disease.

Parkinson's disease (PD) is the fastest growing neurodegenerative disease, but at present there is no cure, nor any disease-modifying treatments. Synaptic biomarkers from in vivo imaging have shown promise in imaging loss of synapses in PD and other neurodegenerative disorders. Here, we provide new clinical insights from a cross-sectional, high-resolution positron emission tomography (PET) study of 30 PD individuals and 30 age- and sex-matched healthy controls (HC) with the radiotracer [11C]UCB-J, which binds to synaptic vesicle glycoprotein 2A (SV2A), and is therefore, a biomarker of synaptic density in the living brain. We also examined a measure of relative brain perfusion from the early part of the same PET scan. Our results provide evidence for synaptic density loss in the substantia nigra that had been previously reported, but also extend this to other early-Braak stage regions known to be affected in PD (brainstem, caudate, olfactory cortex). Importantly, we also found a direct association between synaptic density loss in the nigra and severity of symptoms in patients. A greater extent and wider distribution of synaptic density loss in PD patients with longer illness duration suggests that [11C]UCB-J PET can be used to measure synapse loss with disease progression. We also demonstrate lower brain perfusion in PD vs. HC groups, with a greater extent of abnormalities in those with longer duration of illness, suggesting that [11C]UCB-J PET can simultaneously provide information on changes in brain perfusion. These results implicate synaptic imaging as a useful PD biomarker for future disease-modifying interventions.

ASCL2 is a key regulator of the proliferation-differentiation equilibrium in the esophageal epithelium.

The esophagus is protected from the hostile environment by a stratified epithelium, which renews rapidly. Homeostasis of this epithelium is ensured by a rare population of stem cells in the basal layer: Keratin 15+ (Krt15+) cells. However, little is known about the molecular mechanisms regulating their distinct features, namely self-renewal, potency and epithelial regeneration. Achaete-scute family BHLH transcription factor 2 (ASCL2) is strongly upregulated in Krt15+ stem cells and is known to contribute to stem cell maintenance in other tissues. Herein, we investigated the role of ASCL2 in maintaining homeostasis under normal and stress conditions in the esophageal epithelium. ASCL2 overexpression severely dysregulated cell differentiation and cell fate. Proliferation was also reduced due potentially to a blockage in the G1 phase of the cell cycle or an induction of quiescence. Mass spectrometry analysis confirmed alterations in several proteins associated with differentiation and the cell cycle. In addition, overexpression of ASCL2 enhanced resistance to radiation and chemotherapeutic drugs. Overall, these results denote the role of ASCL2 as a key regulator of the proliferation-differentiation equilibrium in the esophageal epithelium.

Elemental composition of grass phytoliths: Environmental control and effect on dissolution.

Plant phytoliths, which represent the main pool of silica (Si) in the form of hydrous Si oxide, are capable of providing valuable information on different aspect of environmental issues including paleo-environmental reconstruction and agricultural sustainability. Phytoliths may have different chemical composition, which, in turn, affects their preservation in soils ad impacts terrestrial cycle of the occluded elements including micro-nutrients and environmental toxicants. Yet, in contrast to sizable work devoted to phytoliths formation, dissolution and physico-chemical properties, the mechanisms that control total (major and trace) elemental composition and the impact that various elements exert on phytolith reactivity and preservation in soils remains poorly known. In order to fil this gap in knowledge, here we combined two different approaches - analytical trace element geochemistry and experimental physical chemistry. First, we assessed full elemental composition of phytoliths from different plants via measuring major and trace elements in 9 samples of grasses collected in northern Eurasia during different seasons, 18 grasses from Siberian regions, and 4 typical Si-concentrating plants (horsetail, larch, elm and tree fern). We further assessed the dissolution rates of phytoliths exhibiting drastically different concentrations of trace metals. In the European grasses, the variations of phytolith chemical composition among species were highly superior to the variations across vegetative season. Compared to European samples, Siberian grass phytoliths were impoverished in Ca and Sr, exhibited similar concentrations of Li, B, Na, Mg, K, V, Zn, Ni, Mo, As, Ba, and U, and were strongly enriched (x 100-1000) in lithogenic elements (trivalent and tetravalent hydrolysates), P, Mn, Fe and divalent metals. Overall, the variations in elemental composition between different species of the same region were lower compared to variations of the same species from distant regions. The main factors controlling phytoliths elemental composition are the far-range atmospheric (dust) transfer, climatic conditions (humidity), and, in a lesser degree, local lithology and anthropogenic pollution. Despite significant, up to 3 orders of magnitude, difference in TE composition of grass and other plant phytoliths, the dissolution rates of grass phytoliths measured in this study were similar, within the experimental uncertainty, to those of other plants studied in former works. Therefore, elemental composition of phytoliths has relatively minor impact on their preservation in soils.

Nutrition in Women at High Altitude: A Scoping Review-UIAA Medical Commission Recommendations.

Andjelkovic, Marija, Peter Paal, Susi Kriemler, Kaste Mateikaite-Pipiriene, Alison Rosier, Beth Beidleman, Mia Derstine, Jacqueline Pichler Hefti, David Hillebrandt, Lenka Horakova, Dominique Jean, and Linda E. Keyes. Nutrition in women at high altitude: a scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 25:9-15, 2024. Background: Nutritional concerns such as food composition, energy intake, and nutrient absorption are essential for performance at high altitude and may differ between men and women. We performed a scoping review to summarize what is currently known on nutrition for women during short-term, high-altitude, physically active sojourns. Methods: The UIAA Medical Commission convened an international team to review women's health issues at high altitude and to publish updated recommendations. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including nutrition, metabolism, energy composition, micronutrients) with additional publications found by hand search. Results: We found 7,165 articles, of which 13 original articles assessed nutritional aspects in physically active women on short-term high-altitude sojourns, with other articles found by hand search. We summarize the main findings. Conclusions: Data on women's nutrition at altitude are very limited. Reduction in energy intake plus increased energy expenditure at high altitude can lead to unbalanced nutrition, negatively influencing high-altitude adaptation and physical performance. Therefore, adequate dietary and fluid intake is essential to maintaining energy balance and hydration at high altitude in women as in men. Iron supplementation should be considered for women with iron depletion before travel.

The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J.

PURPOSE: Aging is a major societal concern due to age-related functional losses. Synapses are crucial components of neural circuits, and synaptic density could be a sensitive biomarker to evaluate brain function. [11C]UCB-J is a positron emission tomography (PET) ligand targeting synaptic vesicle glycoprotein 2A (SV2A), which can be used to evaluate brain synaptic density in vivo. METHODS: We evaluated age-related changes in gray matter synaptic density, volume, and blood flow using [11C]UCB-J PET and magnetic resonance imaging (MRI) in a wide age range of 80 cognitive normal subjects (21-83 years old). Partial volume correction was applied to the PET data. RESULTS: Significant age-related decreases were found in 13, two, and nine brain regions for volume, synaptic density, and blood flow, respectively. The prefrontal cortex showed the largest volume decline (4.9% reduction per decade: RPD), while the synaptic density loss was largest in the caudate (3.6% RPD) and medial occipital cortex (3.4% RPD). The reductions in caudate are consistent with previous SV2A PET studies and likely reflect that caudate is the site of nerve terminals for multiple major tracts that undergo substantial age-related neurodegeneration. There was a non-significant negative relationship between volume and synaptic density reductions in 16 gray matter regions. CONCLUSION: MRI and [11]C-UCB-J PET showed age-related decreases of gray matter volume, synaptic density, and blood flow; however, the regional patterns of the reductions in volume and SV2A binding were different. Those patterns suggest that MR-based measures of GM volume may not be directly representative of synaptic density.

Menopause and High Altitude: A Scoping Review-UIAA Medical Commission Recommendations.

Mateikaite-Pipiriene, Kaste, Dominique Jean, Peter Paal, Lenka Horakova, Susi Kriemler, Alison J. Rosier, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, Jacqueline Pichler Hefti, David Hillebrandt, and Linda E. Keyes for the UIAA MedCom writing group on Women's Health in the Mountains. Menopause and high altitude: A scoping review-UIAA Medical Commission Recommendations. High Alt Med Biol. 25:1-8, 2024. Background: Older people are an important fraction of mountain travelers and climbers, many of them postmenopausal women. The aim of this work was to review health issues that older and postmenopausal women may experience at high altitude, including susceptibility to high-altitude illness. Methods: We performed a scoping review for the UIAA Medical Commission series on Women's Health in the mountains. We searched PubMed and Cochrane libraries and performed an additional manual search. The primary search focused on articles assessing lowland women sojourning at high altitude. Results: We screened 7,165 potential articles. The search revealed three relevant articles, and the manual search another seven articles and one abstract. Seven assessed menopausal low-altitude residents during a high-altitude sojourn or performing hypoxic tests. Four assessed high-altitude residents. We summarize the results of these 11 studies. Conclusions: Data are limited on the effects of high altitude on postmenopausal women. The effects of short-term, high-altitude exposure on menopause symptoms are unknown. Menopause has minimal effect on the physiological responses to hypoxia in physically fit women and does not increase the risk of acute mountain sickness. Postmenopausal women have an increased risk of urinary tract infections, which may be exacerbated during mountain travel. More research is needed on the physiology and performance of older women at high altitude.

Women's Health at High Altitude: An Introduction to a 7-Part Series by the International Climbing and Mountaineering Federation Medical Commission.

Horakova, Lenka, Peter Paal, Jacqueline Pichler Hefti, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, David Hillebrandt, Dominique Jean, Kaste Mateikaite-Pipiriene, Alison J. Rosier, Susi Kriemler, and Linda E. Keyes. Women's health at high altitude: An introduction to a 7-part series by the International Climbing and Mountaineering Federation Medical Commission. High Alt Med Biol. 24:243-246, 2023. Background: Women have been traveling to high altitude since the inception of modern mountaineering. Although there are distinct female-specific features such as menstruation and menopause relevant to adaptation to and performance at high altitude, very little data exist on women's high-altitude health. To summarize what is known to date, the Medical Commission of the International Climbing and Mountaineering Federation (UIAA) has created a series of articles on women's health, high altitude illness, and performance at high altitude. Methods: Assembling an international author team, two types of manuscripts were developed: (1) reviews on female-specific topics such as pregnancy; (2) reviews on sex differences in high-altitude related illnesses, nutrition, cold injuries, and mortality. Results: The literature search yielded 7,165 articles, with 482 studies meeting the inclusion criteria for full-text review. The authors of individual chapters reviewed these articles and performed additional hand searches. Conclusions: Some important questions on women sojourning and exercising at high altitude have been studied, but many are still awaiting a qualified and evidence-based response. Our seven reviews, to be published in future issues of this journal, summarize what is known about lowland women sojourning at high altitude, provide recommendations, and highlight knowledge gaps in high altitude women's medicine.

High-Altitude Pulmonary Edema in Women: A Scoping Review-UIAA Medical Commission Recommendations.

Pichler Hefti, Jacqueline, Dominique Jean, Alison Rosier, Mia Derstine, David Hillebrandt, Lenka Horakova, Linda E. Keyes, Kaste Mateikaite-Pipiriene, Peter Paal, Marija Andjelkovic, Beth Beidlemann, and Susi Kriemler. High-altitude pulmonary edema in women: a scoping review-UIAA Medical Commission Recommendations. High Alt Med Biol. 24:268-273, 2023. Background: High-altitude pulmonary edema (HAPE) can occur >2,500-3,000 m asl and is a life-threatening medical condition. This scoping review aims to summarize the current data on sex differences in HAPE. Methods: The International Climbing and Mountaineering Federation (UIAA) Medical Commission convened an international author team to review women's health issues at high altitude. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including HAPE), with additional publications found by hand search. The primary search focus was for original articles that included minimum one woman and at least a rudimentary subgroup analysis. Results: The literature search yielded 7,165 articles, 416 of which were relevant for HAPE, and 7 of which were ultimately included here. Six were case series, consistently reporting a lower HAPE prevalence in women. The one retrospective case-control study reported male HAPE prevalence at 10/100,000 and female at 0.74/100,000. No studies were identified that directly compared sex differences in the prevalence of HAPE. No published data was found for topics other than epidemiology. Conclusions: Few studies and associated methodological limitations allow few conclusions to be drawn. Incidence of HAPE may be lower in women than in men. We speculate that besides physiological aspects, behavioral differences may contribute to this potential sex difference.

Acute Mountain Sickness and High Altitude Cerebral Edema in Women: A Scoping Review-UIAA Medical Commission Recommendations.

Derstine, Mia, Dominique Jean, Beth A. Beidleman, Jacqueline Pichler Hefti, David Hillebrandt, Lenka Horakova, Susi Kriemler, Kasté Mateikaité-Pipiriené, Peter Paal, Alison Rosier, Marija Andjelkovic, and Linda E. Keyes. Acute mountain sickness and high altitude cerebral edema in women: A scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 24:259-267, 2023. Background: Acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) are illnesses associated with rapid ascent to altitudes over 2,500 m in unacclimatized lowlanders. The aim of this scoping review is to summarize the current knowledge on sex differences in the epidemiology, pathophysiology, symptomatology, and treatment of AMS and HACE, especially in women. Methods and Results: The UIAA Medical Commission convened an international author team to review women's health issues at high altitude and to publish updated recommendations. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including AMS, HACE, and high altitude), with additional publications found by hand search. The primary search focus was for articles assessing lowland women sojourning at high altitude. Results: The literature search yielded 7,165 articles, 37 of which were ultimately included. The majority of publications included did not find women at increased risk for AMS or HACE. There was extremely limited sex-specific data on risk factors or treatment. Conclusions: There is a limited amount of data on female-specific findings regarding AMS and HACE, with most publications addressing only prevalence or incidence with regard to sex. As such, general prevention and treatment strategies for AMS and HACE should be used regardless of sex.

ZNF432 stimulates PARylation and inhibits DNA resection to balance PARPi sensitivity and resistance.

Zinc finger (ZNF) motifs are some of the most frequently occurring domains in the human genome. It was only recently that ZNF proteins emerged as key regulators of genome integrity in mammalian cells. In this study, we report a new role for the Krüppel-type ZNF-containing protein ZNF432 as a novel poly(ADP-ribose) (PAR) reader that regulates the DNA damage response. We show that ZNF432 is recruited to DNA lesions via DNA- and PAR-dependent mechanisms. Remarkably, ZNF432 stimulates PARP-1 activity in vitro and in cellulo. Knockdown of ZNF432 inhibits phospho-DNA-PKcs and increases RAD51 foci formation following irradiation. Moreover, purified ZNF432 preferentially binds single-stranded DNA and impairs EXO1-mediated DNA resection. Consequently, the loss of ZNF432 in a cellular system leads to resistance to PARP inhibitors while its overexpression results in sensitivity. Taken together, our results support the emerging concept that ZNF-containing proteins can modulate PARylation, which can be embodied by the pivotal role of ZNF432 to finely balance the outcome of PARPi response by regulating homologous recombination.