THE IMPACT OF BIRTH WEIGHT ON INFANT MORTALITY IN KAZAKHSTAN.

INTRODUCTION: Recognizing the importance of birth weight is fundamental to addressing public health challenges associated with maternal and child health. Birth weight serves as a critical indicator, offering insights into mortality, stunting, and the development of chronic diseases later in life. This study delves into fertility and infant mortality trends in Kazakhstan, with a specific focus on understanding urban-rural disparities and gender variations in mortality rates. OBJECTIVES: The primary objective of this study is to evaluate the influence of birth weight on infant mortality in Kazakhstan, considering demographic and regional nuances. Through comprehensive analysis, we aim to discern patterns and factors contributing to infant mortality, thereby informing targeted interventions and policies aimed at improving maternal and child health outcomes across the country. MATERIALS AND METHODS: The analysis was conducted using the data provided by the Republican State Enterprise on the PCV of the "Republican Centre for Electronic Health Care" of the Ministry of Health of Kazakhstan. RESULTS: In Kazakhstan, birth rates reached their zenith in 2021 (total 446,491 births). However, this figure experienced a downturn in 2022, declining to 403,893 births. Notably, urban regions consistently reported higher birth rates compared to rural areas. The year 2022 witnessed a decline in birth rates across both urban and rural populations, with decreases of 9.5% and 11.7%, respectively, compared to the previous year. Analysis using linear regression techniques on infant mortality rates spanning from 2017 to 2022 revealed no statistically significant time trend (slope=51.29, correlation coefficient=0.42, p=0.41). Gender-specific disparities in mortality rates were starkly evident, with boys exhibiting higher mortality rates compared to girls across all population subsets. Geographical analysis conducted in 2022 exposed significant divergences in mortality rates across various regions. CONCLUSIONS: The study highlights significant urban-rural disparities and gender differences in birth rates and infant mortality within Kazakhstan. It also confirms the protective effect of higher birth weight on infant mortality. Regional disparities suggest targeted public health interventions are necessary to address these variations effectively.

Insertable, dual-density dielectric barrier for acoustic pressure level reduction in a high-performance human head-only MRI system.

We report use of a dual-density dielectric barrier surrounding a detachable high-pass radiofrequency (RF) birdcage coil to achieve an order-of-magnitude reduction of acoustic noise in a high-performance head gradient system. The barrier consisted of a 4.5 mm-thick mass-loaded vinyl and a 6 mm-thick polyurethane foam. It was inserted into the radial gap between the birdcage coil and the RF shield in a prototype head-only gradient system at 3 T. More than 9 dBA reduction of sound pressure level was achieved on the average with representative, high acoustic-noise imaging sequences. Increased acoustic damping was apparent from acoustic impulse response functions. High dielectric constant of the mass-loaded vinyl effectively added distributed capacitance to the birdcage coil, lowering the resonance frequency, but not seriously degrading the RF transmission performance. The barrier occupied the radial space normally used for air cooling of the RF coil and the RF shield. The resulting omission of air cooling was found to be acceptable with efficient gradient thermal management and use of a high-resistivity RF shield for eddy current reduction. The proposed method can improve patient experience while preserving image quality in a high-power head-only gradient system.

Guidelines for communicating commensurate magnetic structures. A report of the International Union of Crystallography Commission on Magnetic Structures.

A report from the International Union of Crystallography Commission on Magnetic Structures outlining the recommendations for communicating commensurate magnetic structures.

Engaging oncology and occupational medicine to inform design of a Total Worker Health® intervention to address employment, financial, and well-being outcomes in cancer survivors.

OBJECTIVES: Few Total Worker Health® studies, and fewer interventions, examine well-being in the work context of cancer survivorship. We investigated the possibility of occupation and oncology professionals working together to address employed survivors' work-associated needs. METHODS: We employed a community-based participatory research (CBPR) approach to examine the educational, contextual, and workflow needs of oncology care team members to inform intervention design. Focus groups were conducted with oncology care team members and occupational medicine physicians. Key themes from each group were then examined. RESULTS: Themes included oncology care team's role in helping patients navigate resources, providing psychosocial support, and educating patients. Major themes for ways to better provide employment-related support during treatment included referring patients to employment experts and providing education on employment support. CONCLUSIONS: Occupational health professionals in collaboration with oncology clinics could play an important role in assisting cancer survivors' ability to navigate employment challenges.

Distinct subcircuits within the mesolimbic dopamine system encode the salience and valence of social stimuli.

The mesolimbic dopamine (DA) system (MDS) is the canonical "reward" pathway that has been studied extensively in the context of the rewarding properties of sex, food, and drugs of abuse. In contrast, very little is known about the role of the MDS in the processing of the rewarding and aversive properties of social stimuli. Social interactions can be characterized by their salience (i.e., importance) and their rewarding or aversive properties (i.e., valence). Here, we test the novel hypothesis that projections from the medial ventral tegmental area (VTA) to the nucleus accumbens (NAc) core codes for the salience of social stimuli through the phasic release of DA in response to both rewarding and aversive social stimuli. In contrast, we hypothesize that projections from the lateral VTA to the NAc shell codes for the rewarding properties of social stimuli by increasing the tonic release of DA and the aversive properties of social stimuli by reducing the tonic release of DA. Using DA amperometry, which monitors DA signaling with a high degree of temporal and anatomical resolution, we measured DA signaling in the NAc core or shell while rewarding and aversive social interactions were taking place. These findings, as well as additional anatomical and functional studies, provide strong support for the proposed neural circuitry underlying the response of the MDS to social stimuli. Together, these data provide a novel conceptualization of how the functional and anatomical heterogeneity within the MDS detect and distinguish between social salience, social reward, and social aversion. Significance Statement: Social interactions of both positive and negative valence are highly salient stimuli that profoundly impact social behavior and social relationships. Although DA projections from the VTA to the NAc are involved in reward and aversion little is known about their role in the saliency and valence of social stimuli. Here, we report that DA projections from the mVTA to the NAc core signal the salience of social stimuli, whereas projections from the lVTA to the NAc shell signal valence of social stimuli. This work extends our current understanding of the role of DA in the MDS by characterizing its subcircuit connectivity and associated function in the processing of rewarding and aversive social stimuli.

Developing molecular classifiers to detect environmental stressors, smolt stages and morbidity in coho salmon, Oncorhynchus kisutch.

Aquatic species are increasingly confronted with environmental stressors because of climate change. Although molecular technologies have advanced our understanding of how organisms respond to stressors in laboratory settings, the ability to detect physiological responses to specific stressors under complex field conditions remains underdeveloped. This research applied multi-stressor challenge trials on coho salmon, employing the "Salmon Fit-Chips" genomic tool and a random forest-based classification model to develop classifiers predictive for chronic thermal and hypoxic stress, as well as salinity acclimation, smolt stage and morbidity status. The study also examined how smolts and de-smolts (smolts not having entered SW during the smolt window) responded transcriptionally to exposure to saltwater. Using RF classifiers optimized with 4 to 12 biomarkers, we identified transcriptional signatures that accurately predicted the presence of each stressor and physiological state, achieving prediction accuracy rates between 86.8 % and 100 %, regardless of other background stressors present. Stressor recovery time was established by placing fish back into non-stressor conditions after stress exposure, providing important context to stressor detections in field applications. Recovery from thermal and hypoxic stress requires about 3 and 2 days, respectively, with >3 days needed for re-acclimation to freshwater for seawater acclimated fish. The study also found non-additive (synergistic) effects of multiple stressors on mortality risk. Importantly, osmotic stress associated with de-smolts was the most important predictor of mortality. In saltwater, de-smolts exposed to salinity, high temperature, and hypoxia experienced a 9-fold increase in mortality compared to those only exposed to saltwater, suggesting a synergistic response to multiple stressors. These findings suggest that delays in hatchery releases to support release of larger fish need to be carefully scrutinized to ensure fish are not being released as de-smolts, which are highly susceptible to additional climate-induced stressors like rising temperatures and reduced dissolved oxygen levels in the marine environment.

Exercise related versus non exercise related out of hospital cardiac arrest - A retrospective single-center study.

Background: Physical activity prevents cardiovascular disease, but it may also trigger acute cardiac events like sudden cardiac death in patients with underlying heart disease. The chance of surviving an out-of-hospital cardiac arrest remains low, despite improving medical treatment and rescue chain. Prior studies signaled increased survival in exercise related out-of-hospital cardiac arrest. Objective: The aim of this study was to evaluate the differences between exercise related out-of-hospital cardiac arrest and out-of-hospital cardiac arrest during daily activity in an urban setting. Methods: Retrospective analysis of all out-of-hospital cardiac arrests from 2014 to 2021 treated at a cardiac arrest center of a tertiary hospital. The primary outcome was survival to discharge. Secondary outcomes included differences in pre-hospital care, in-hospital treatment, hypoxic ischemic encephalopathy, and laboratory parameters. Results: 478 OHCA patients were reviewed of which 432 patients (exercise related 36 (8.4%) vs. daily activity 396 (91.6%)) were included in the analysis. Patients suffering an exercise related arrest were younger (57 vs 65 years, p = 0.002) and mostly male (88.9 vs 74.5%, p = 0.054).The exercise related cohort received bystander cardiopulmonary resuscitation (77.8 vs 53.4%, p = 0.005) to a higher extent and had a shorter no-flow time (1.5 vs 2 min, p = 0.049). Exercise related arrest patients more often presented with a shockable rhythm (80.6 vs 64.1%, p = 0.032).At hospital admission exercise related arrest patients had a higher initial pH (7.24 vs 7.19, p = 0.015). In the exercise related group, a cardiac cause was numerically more frequent compared to the daily activity group (80.6 vs 68.7%, p = 0.09). In both groups myocardial infarction (47.2 vs 43.2%) was the most common cause, but a primary arrhythmic event (33.3 vs 25.5%) was more often documented in exercise related arrest patients. Exercise related arrest was mostly related to endurance training (52.8%) followed by ball sports (19.4%) and occurred directly during exercise in 77.8% of cases. Patients suffering exercise related arrest had higher survival till discharge (66.7 vs 47.7%, p = 0.036). Conclusion: Based on this observational data from a highly selected group of out-of-hospital cardiac arrest patients treated at a cardiac arrest center, patients suffering an exercise related out-of-hospital cardiac arrest, differed in substantial characteristics and in the first line response compared to daily activity out-of-hospital cardiac arrest patients. The better survival to discharge of the exercise related out-of-hospital cardiac arrest group might be driven by these beneficial differences. This study underlines the need for public awareness for the importance of a fast first response and a broad distribution of automated external defibrillators in public sport areas since most of the exercise related out-of-hospital cardiac arrest patients presented with a cardiac cause and an initial shockable rhythm.

A longitudinal assessment of heat exposure and biomarkers of kidney function on heat shock protein 70 and antibodies among agricultural workers.

BACKGROUND: Exposure to extreme heat impacts millions of people worldwide and outdoor workers are among the populations most affected by hot temperatures. Heat stress induces several biological responses in humans, including the production of heat shock proteins (HSP) and antibodies against HSP (anti-HSP) which may play a central role in the body's cellular response to a hot environment. OBJECTIVE: This longitudinal study investigated the impact of elevated temperatures and humidity on the presence of HSP70 and anti-HSP70 and examined relationships with markers of kidney function in an at-risk workforce under conditions of extreme heat and exertion in Guatemala. METHODS: We collected ambient temperature and relative humidity data as well as biomarkers and clinical data from 40 sugarcane workers at the start and the end of a 6-month harvest. We used generalized mixed-effects models to estimate temperature effects on HSP70 and anti-HSP70 levels. In addition, we examined trends between HSP70 and anti-HSP70 levels and markers of kidney function across the harvest. RESULTS: At the end of the harvest, temperatures were higher, and workers had, on average, higher levels of HSP70 and anti-HSP70 compared to the beginning of the season. We observed significant increasing trends with temperature indices, heat index, and HSP70 levels. Maximum temperature was associated with HSP70 increments after controlling for age, systolic and diastolic blood pressure (ß: 0.21, 95% Confidence Interval: 0.09, 0.33). Kidney function decline across the harvest was associated with both higher levels of anti-HSP70 levels at the end of the harvest as well as greater increases in anti-HSP70 levels across the harvest. CONCLUSIONS: These results suggest that workplace heat exposure may increase the production of HSP70 and anti-HSP70 levels and that there may be a relationship between increasing anti-HSP70 antibodies and the development of renal injury. HSP70 holds promise as a biomarker of heat stress in exposed populations.

The transmembrane domain of the rice small protein OsS1Fa1 is responsible for subcellular localization and drought tolerance.

OsS1Fa1, a homologue of spinach S1Fa, is a small protein in rice that contains four distinct conserved motifs and participates in drought tolerance. However, the biological functions of these conserved motifs have not been characterized to date. Therefore, we investigated the roles of these conserved domains in the localization and cellular function of OsS1Fa1. We analysed the subcellular localization of OsS1Fa1 using confocal laser scanning microscopy (CLSM), following particle bombardment and bacterial infiltration. An E. coli in vivo reconstituted sumoylation assay was conducted to investigate sumoylation of OsS1Fa1. We characterized the function of the transmembrane domain of OsS1Fa1 in drought tolerance using transgenic Arabidopsis plants. Fluorescence analysis showed that OsS1Fa1 localized to the nuclear and cytoplasmic membranes. Mutation and cell fractionation analyses revealed that the membrane localization domain determined the subcellular localization of OsS1Fa1. The rice homologue OsS1Fa2 and Arabidopsis orthologs AtS1Fa1, AtS1Fa2, and AtS1Fa3 also exhibited similar localization patterns as OsS1Fa1. Sumoylation analysis demonstrated that OsS1Fa1 was conjugated with the small ubiquitin-related modifier (SUMO). Transgenic analysis showed that overexpression of OsS1Fa1(TMm1), a mutant form of the transmembrane domain of OsS1Fa1, in Arabidopsis did not enhance drought stress tolerance, whereas OsS1Fa1 overexpression improved the drought tolerance of transgenic Arabidopsis. Our data indicate that rice and Arabidopsis S1Fa1 proteins localize in the nuclear and cytoplasmic membranes, and that transmembrane domain determines subcellular localization and plays an important role in drought stress tolerance.

A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19-17).

BACKGROUND: We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification. PATIENTS AND METHODS: A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR). For exploratory analyses, we analyzed the gene profiles using plasma NGS test. RESULTS: Thirty-five patients were enrolled. The ORR was 57.6% for all patients, 52.2% for those with METex14, and 70% for those with MET amplification. Median progression-free survival (PFS) was 8 months [95% confidence interval (CI) 4.5-11.5 months] and median overall survival (OS) was 14 months (95% CI 7.8-20.2 months) in all patients. For patients with non-small-cell lung cancer with METex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months [95% CI not applicable (NA)-NA]. For patients with MET amplification, the median PFS was 7 months (95% CI 1.5-12.5 months) and the median OS was 10 months (95% CI 5.8-14.2 months). The ORR of patients with MET dysregulation detected by plasma NGS was 72.2%, whereas the ORR was 30% in those without detection. The most common adverse events were peripheral edema, asthenia, transaminase elevation, and anorexia, mostly grade 1 or 2. CONCLUSIONS: Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.

Ocular findings in Jansen metaphyseal chondrodysplasia.

Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by germline heterozygous PTHR1 variants resulting in constitutive activation of parathyroid hormone type 1 receptor. A description of ocular manifestations of the disease is lacking. Six patients with JMC underwent a detailed ophthalmic evaluation, spectral-domain optical coherence tomography (OCT), visual field testing, and craniofacial CT scans. Five of 6 patients had good visual acuity. All patients had widely spaced eyes; 5/6 had downslanted palpebral fissures. One patient had proptosis, and another had bilateral ptosis. Two patients had incomplete closure of the eyelids (lagophthalmos), one had a history of progressive right facial nerve palsy with profuse epiphora, while the second had advanced optic nerve atrophy with corresponding retinal nerve fiber layer (RNFL) thinning on OCT and significant bilateral optic canal narrowing on CT scan. Additionally, this patient also had central visual field defects and abnormal color vision. A third patient had normal visual acuity, subtle temporal pallor of the optic nerve head, normal average RNFL, but decreased temporal RNFL and retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4/6 patients indicating a subclinical optic nerve atrophic process. None of the patients had glaucoma or high myopia. These data represent the first comprehensive report of ophthalmic findings in JMC. Patients with JMC have significant eye findings associated with optic canal narrowing due to extensive skull base dysplastic bone overgrowth that appear to be more prevalent and pronounced with age. Progressive optic neuropathy from optic canal narrowing may be a feature of JMC, and OCT GCA can serve as a useful biomarker for progression in the setting of optic canal narrowing. We suggest that patients with JMC should undergo regular ophthalmic examination including color vision, OCT, visual field testing, orbital, and craniofacial imaging.

Characterization of concrete reference material for analysis of artificial radionuclides in nuclear power plant decommissioning waste.

The decommissioning of nuclear power plants has led to a surge in the production of radioactive waste, necessitating the development of accurate and reliable measurement methods for safe waste disposal. This study presents the development of a new concrete reference material (RM) containing beta, and gamma nuclides for quality assurance and quality control (QA/QC) in concrete measurements. The newly developed RM manufacturing method was used to ensure sample homogeneity; rigorous processes were followed according to ISO guidelines. The RM, designed to mimic real waste matrices, targeted six radionuclides: 60Co, 134Cs, 137Cs, 152Eu, 154Eu, and 90Sr. Homogeneity and stability tests, conducted according to ISO guidelines, confirmed the suitability of the concrete RM for QA/QC purposes. Reference values for the six radionuclides in RM ranged from 66.0 to 172.6 Bq kg-1. The expanded uncertainties of the reference values, at a 95 % confidence level (k = 2), ranged from approximately 7.1 %-17.2 %. The developed RM holds potential as proficiency test material and for validating and verifying analytical methods in radioactive waste analysis. Additionally, the manufacturing method introduced here opens doors for diverse applications, enabling the production of accurate and reliable reference materials for various waste matrices.

U-PRO-CRM: designing patient-centred dose-finding trials with patient-reported outcomes.

BACKGROUND: Determining the maximum tolerated dose (MTD) remains the primary objective for the majority of dose-finding oncology trials. Whilst MTD determination often relies upon clinicians to identify dose-limiting toxicities (DLTs) experienced by patients during the trial, research suggests that clinicians may underreport patient's adverse events. Therefore, contemporary practice may be exposed to recommending intolerable doses to patients for further investigation in subsequent trials. There is increasing interest in patients self-assessing their own symptoms using patient-reported outcomes (PROs) in dose-finding trials. DESIGN: We present Utility-PRO-Continual Reassessment Method (U-PRO-CRM), a novel trial design which simultaneously uses clinician-rated and patient-rated DLTs (Clinician-DLTs and Patient-DLTs, respectively) to make dose (de-)escalation decisions and to recommend an MTD. U-PRO-CRM contains the published PRO-CRM as a special case and provides greater flexibility to trade-off the rate of Patient-DLTs and Clinician-DLTs to find an optimal dose. We present simulation results for U-PRO-CRM. RESULTS: For specified trade-offs between Clinician-DLT and Patient-DLT rate, U-PRO-CRM outperforms the PRO-CRM design by identifying the true MTD more often. In the special case where U-PRO-CRM generalises to PRO-CRM, U-PRO-CRM performs as well as its published counterpart. U-PRO-CRM minimises the number of patients overdosed whilst maintaining a similar proportion of patients allocated to the true MTD. CONCLUSIONS: By using a utility-based dose selection approach, U-PRO-CRM offers the flexibility to define a trade-off between the risk of patient-rated and clinician-rated DLTs for an optimal dose. Patient-centric dose-finding strategies, which integrate PROs, are poised to assume an ever more pivotal role in significantly advancing our understanding of treatment tolerability. This bears significant implications in shaping the future landscape of early-phase trials.

Increased risk of haematological malignancy in adults over age 60 with thrombocytopenia compared with matched controls: Time for an upfront bone marrow evaluation?

International societies have conflicting recommendations on whether bone marrow aspirate/biopsy (BMB) is needed during workup for isolated thrombocytopenia. Our objective was to determine if thrombocytopenia in patients aged ≥60 years is associated with an increased incidence of haematological malignancy. We performed a retrospective population-based cohort study in patients aged ≥60 years between January 1, 2009 to December 31, 2019. Exposed patients had specialist consultation for thrombocytopenia, with platelet count <100 × 109/L, but normal haemoglobin and white blood cell count. Unexposed patients were those who never had specialist consultation for thrombocytopenia and whose platelets were ≥100 × 109/L. The primary outcome was the diagnosis of haematological malignancy using a competing risk of death model. During 4.0 years (IQR 2.2-6.7) of follow-up, 378/4930 exposed (19.1/1000PY, 95% CI 17.1-21.0), and 204/17556 unexposed patients (2.5/1000PY, 95% CI 2.2-2.8) were diagnosed with haematological malignancy (HR 15.5 (95% CI 11.3-21.4, p < 0.0001) in year 1, and 5.3 (95% CI 4.4-6.6, p < 0.0001) in years 2+). This finding persisted in analyses stratified by sex, age, severity, or duration of thrombocytopenia, and treatment with corticosteroids within 2 weeks of consultation. This study found a strong association between isolated thrombocytopenia and haematological malignancy in patients ≥60 years, supporting consideration of diagnostic testing including BMB during outpatient specialist consultation.