Loss Of Reserve Research Articles

Association between frailty, chronic conditions and socioeconomic status in community-dwelling older adults attending primary care: a cross-sectional study using practice-based research network data

ObjectivesFrailty is a multidimensional syndrome of loss of reserves in energy, physical ability, cognition and general health. Primary care is key in preventing and managing frailty, mindful of the social...

The Frail Elderly Patient and the Need for a Video Store on Regional Anaesthesia Blocks

The Frail Elderly Patient and the Need for a Video Store on Regional Anaesthesia Blocks

Quantitative and Qualitative Characteristics of Organic Matter Under Long-Term Exposure to Natural and Anthropogenic Factors

Studies have found that the increase in differences between the amount of energy subsidies invested in agrobiocenoses and alienated from them over a 105-year period changes the direction of biochemical processes of organic matter transformation, which leads to significant losses of organic carbon reserves, which amount to 17.5 t/ha in highly degraded soils, 7.3 t/ha in poorly cultivated soils, and in highly cultivated increases them by 2.8 t /ha, respectively, compared with the initial content. Long-term use of arable land affects the qualitative characteristics of the state of organic matter of sod-podzolic soil, which are expressed in a change in the ratio of the peripheral and central parts, the enrichment of humus with nitrogen. The humus substances of medium (57%) and highly cultivated soils (54%) are characterized by the highest degree of participation of peripheral groupings in the construction, and the least highly degraded (29%).

Удосконалення технології розбирання металоконструкцій механізованого шахтного кріплення

During operation, the hinge connections of mine supports practically stop rotating. This is due to the fact that, as a result of the aggressive mine water and strong dustiness, the diametrical clearance of 1-2 mm between the axis and the bushing is tightly filled with oxides and coal dust, especially in the connections of the base. This circumstance leads to the fact that the axes (pins) in the hinges lose their mobility and require significant effort for their dismantling. To repair the mechanized mine support, it is necessary to dismantle the hinge connections, which are formed by axes and holes in levers (traverses), base ears, and overlaps. Currently, the dismantling of hinge connections of mine supports is carried out using manual impact tools. This operation is extremely labor-intensive, physically heavy, and belongs to hazardous work. The goal of the study is to improve the working conditions of the operator during the dismantling process of axes in hinge connections of mine supports by using a mechanized specialized hydraulic press. To achieve the set goal, the following tasks must be solved: to determine the maximum permissible disassembly force of the axes, taking into account the strength of the load-bearing structure elements; to develop a concept of a mechanized hydraulic press, including the composition of the installation, the general technical description, the principle of operation, the kinematic scheme, and the tool. Studies have been carried out on the deformation modeling of mine support elements under load using the SOLIDWORKS Simulation calculation module to determine the maximum permissible disassembly force of the axes. It has been shown that the disassembly load of the shaft support axis with a force of more than 1000 kN leads to the loss of the structural strength reserve, which is unacceptable. An effective technology for dismantling the axes of a mechanized mine support has been proposed. A concept of an original specialized hydraulic press "Kit-100" for dismantling axes has been developed, which allows replacing the physically heavy and dangerous work of the operator with a lighter, mechanized process.

Kehilangan Karbon dan Oksigen pada Pemanenan Jati (Tectona grandis Linn. f) Unggul Nusantara di Kebun Percobaan Cogreg, Kecamatan Ciseeng, Kabupaten Bogor

This study aims to calculate the amount of carbon lost and the amount of oxygen that can no longer be produced by the Cogreg Experimental Garden (KPC) due to the harvesting of Nusantara Unggul Teak wood (JUN). Carbon stock loss was measured using the allometric equation method based on the SNI 7724:2011. Calculating the loss of oxygen-producing potential used the comparison method of the atomic weights of carbon and oxygen. The results of this study indicate that the harvesting of JUN at KPC causes a loss of potential carbon storage reserves of 215.384 tons/year or equivalent to IDR7.2 bilions; the loss of oxygen-producing potential is 574,359 tons/year or equivalent to IDR2.66 billions. Meanwhile, the results of harvesting JUN wood can only produce a financial value of IDR1,36 billions. Therefore, the financial value of the KPC's environmental services in the form of carbon storage and oxygen production is much greater than the financial value of harvesting JUN's wood. Keywords: carbon loss, Cogreg Experimental Garden, Jati Unggul Nusantara, oxygen loss

Effect of multiday endurance exercise on total body water and calculated body composition in racing sled dogs

Prolonged multiday exercise in dogs is often associated with a caloric deficit that can lead to changes in body composition but may also result in an increase in lean body mass due to a conditioning effect. To test the hypothesis that multiday exercise decreases fat mass but increases lean body mass, body composition was measured using deuterium oxide dilution in a team of racing Alaskan sled dogs competing in a multiday race. Twelve dogs completed 961 km in 6 days, resulting in a 3% decrease in body mass (P=0.003) and 16% decrease in body fat (P=0.005), and an increase in total body water as a fraction of body mass (P=0.01). Within the study population, there was considerable dog-to-dog variation, with 2 dogs gaining fat mass and 2 dogs losing over 40% of their pre-race fat mass during the measurement period. These results confirm that dogs participating in multiday exercise events are at risk for loss of body fat reserve, likely due to a net calorie deficit. However, individual dog responses to an exercise challenge can be highly variable, emphasizing the need for careful assessment of individual dogs.

DNA Damage Stress Response and Follicle Activation: Signaling Routes of Mammalian Ovarian Reserve.

Chemotherapy regimens and radiotherapy are common strategies to fight cancer. In women, these therapies may cause side effects such as premature ovarian insufficiency (POI) and infertility. Clinical strategies to protect the ovarian reserve from the lethal effect of cancer therapies needs better understanding of the mechanisms underlying iatrogenic loss of follicle reserve. Recent reports demonstrate a critical role for p53 and CHK2 in the oocyte response to different DNA stressors, which are commonly used to treat cancer. Here we review the molecular mechanisms underlying the DNA damage stress response (DDR) and discuss crosstalk between DDR and signaling pathways implicated in primordial follicle activation.

Модифицированный раздел доабортного консультирования

The problem of pregnancy termination is multifaceted. According to the current legislation, women who come to a healthcare facility for an induced termination of pregnancy undergo pre-abortion counseling. During the consultation, the specialist has several tasks: to compare the arguments for pregnancy termination or preservation; to help competently assess the current life situation; to consider ways to solve problems; to provide information about federal and regional support measures for pregnant women and families with children; to inform about possible negative consequences of an artificial termination of pregnancy. The authors believe that in addition to psychological assistance to women in the situation of choice, it is of great importance to provide detailed information about the negative reproductive consequences of abortion, including the problem of premature ovarian insufficiency. Due to the high prevalence of premature ovarian insufficiency among female population, it seems necessary to supplement the existing pre-abortion counseling procedure with a section devoted to the problem of physiological and pathological loss of ovarian reserve and the impact of pregnancy termination on this process. To inform a woman about her risk of premature ovarian insufficiency and about her presence of this condition in general would allow a woman to consciously avoid additional negative influences (smoking, alcohol, stress), make an informed decision about her reproductive plans and their timing, and possibly resort to oocyte cryopreservation methods in cases where the risks of premature ovarian insufficiency are extremely high. When premature ovarian insufficiency is already diagnosed, the only way to have a baby is to use assisted reproductive technology, but with the use of donor eggs.

Absolute coronary flow and microvascular resistances in severe aortic stenosis: invasively quantification

Abstract Background Chest pain in aortic stenosis (AS) has been attributed to the loss of coronary flow reserve however; this has not been directly quantified to date. Purpose To determine whether there is a decrease in coronary flow as a cause of chest pain or dyspnea in patients with severe AS Methods Patients with AS and normal left ventricular ejection fraction (LVEF) underwent coronariography previous to valve replacement. In those patients without obstructive coronary disease, an invasive physiological evaluation was performed to measure absolute coronary flow (Q) and microvascular resistances (R). Left anterior descending artery (LAD) was explored in all cases and, in a subgroup of patients, we also studied the circumflex (CX). Results 51 patients were included. 86% presenting with dyspnea, 26% also reported chest pain, and 11.8% syncope. No patient was admitted due to heart failure. Mean pressure gradient for AS was 52.44±15.41 mmHg with a mean aortic valve area of 0.76±0.17 cm2. Mean LVEF was 63±8.35%. The physiological study of LAD was successfully completed in all patients. 68.6% presented a normal / increased LAD-Q with a mean quantified flow of 262.118±161.99 mL/min. LAD-R proved normal in 56.9% of the cases and low in 13.7%. The quantified mean LAD-R was 400.78±195.89 UW. The physiological study of the CX was carried out in 34 patients. 82.3% presented normal / increased CX-Q, with a mean value of 201.82±117.91 mL/min. CX-R proved normal in 76.5% of the cases and low in 17.6%, with a mean value of 604.147±367.23 UW. Conclusion Invasive intracoronary measurements demonstrated most of patients with severe AS maintain normal values of Q and R Funding Acknowledgement Type of funding sources: None.

Impact of ERACS (Enhanced Recovery After Cardiac Surgery) protocol on clinical outcomes in frail patients undergoing cardiac surgery: First national program in Turkey

Objectives: Enhanced Recovery After Cardiac Surgery (ERACS) is a multidisciplinary, multimodal approach to increase the quality of patient recovery and decrease surgical complications using evidence-based methods. The concept of frailty has generated increased interest in majority of patients with the progressive loss of physiologic reserves, resulting in a state of vulnerability. This study aims to ascertain whether it is feasible to deploy an ERACS protocol in frail patients undergoing cardiac surgery and to document the impact on clinical outcomes.

Indoor Mobility, Frailty, and Disability in Community-Dwelling Older Adults: A Mediation Model.

The general population, but especially older adults, were forced or encouraged to stay home during the recent COVID-19 pandemic. In this context, indoor mobility (IM, the number of steps performed daily at home) may be informative about the general health status of older adults. The present study aimed at evaluating the relationship between IM, frailty (loss of functional reserve including both physical and psychosocial domains), and disability (loss of autonomy measured as activities of daily life, ADLs) in a sample of community-dwelling Italian older adults. Specifically, the primary objective was to investigate IM and disability differences between robust and frail older adults. The secondary objective was to test if frailty is in the causal sequence between IM and disability, i.e., as a mediator in their relationship. Thirty-two participants (mean age = 70 ± 6 years; 56.2% women) were recruited. Frailty and disability were evaluated using the Tilburg Frailty Indicator and the Groningen Activity Restriction Scale, respectively. IM at home was measured via an Adamo wristwatch (a connected accelerometer). One-way analyses of covariance, controlling for age and gender, showed that robust participants, classified according to a score higher than five points in the Tilburg Frailty Indicator, performed significantly more IM (F1,28 = 4.639; p = 0.04) and presented lower disability grade than frail ones (F1,28 = 4.342; p =0.046). Only physical frailty was a mediator in the relationship between IM and disability (F2,29 = 8.538, p < 0.001), with a fully mediated model (z = −2.073, p < 0.04). Conversely, the total frailty score was not a mediator in the same relationship, but with IM accounted for the variance in disability (F2,29 = 8.538, p < 0.001; R2 = 33.7%). Our results suggested that frail older adults restricted their IM more and presented a higher level of disability compared to robust older adults. Moreover, data suggest that IM reduction may have a negative impact on physical frailty and indirectly increase disability.

Sarkopenie, myosteatóza a syndrom křehkosti u pacientů s cirhózou jater

Skeletal muscles are the biggest tissue in healthy people (30–40% of total body mass) and they comprise three quarters of total body proteins. Muscle alterations, especially muscle wasting and loss of muscle function, have an indisputable prognostic value in the outcome of chronic diseases, including chronic liver diseases. Muscle wasting is associated with higher morbidity, mortality and poor quality of life. The terms sarcopenia and myosteatosis are used to describe specific muscle alterations, both forming substantial components of multidimensional construct “frailty syndrome”. Sarcopenia is defined as loss of muscle mass and/or loss of muscle function. It is usually dia­gnosed using the skeletal muscle index from computed tomography (CT) image analysis at the L3 vertebra. Myosteatosis is defined as an excess intramyocelullar and intermyocellular fat deposition. Dia­gnosis of myosteatosis is based on a measurement of skeletal muscle density by CT imaging at the L3 vertebra (skeletal muscle radiation attenuation – SM-RA). Besides muscle alterations and decreased physical performance, frailty syndrome also comprises changes of other organ systems, leading to the loss of functional reserves and higher vulnerability. Different scoring systems, such as Fried Frailty Index (FFI) or modified Liver Frailty Index (LFI) for patients with liver cirrhosis, are used to dia­gnose patients with frail phenotype. The principle of the treatment of patients with muscle alterations is therapy of liver disease (including liver transplant in advanced cirrhosis), improvement of the nutritional status, adequate physical activity and supplementation of vitamin D deficiency, if necessary. In this review, we summarize up-to-date knowledge about pathophysiology, dia­gnostic tools and treatment options of sarcopenia, myosteatosis and frailty syndrome in patients with liver cirrhosis. Key words: sarcopenia – myosteatosis – frailty syndrome – liver cirrhosis

Integrated analysis of clinical, bioelectrical and functional variables in newly diagnosed lung cancer adult patients: pilot study

BackgroundMany variables have been studied in cancer patients. Nevertheless, an study that analyzes simultaneously physical, functional and biological variables in they from clinical, physical and statistical points of views is not reported in the literature. The aim of this study is to propose an integrated analysis of clinical, bioelectrical and functional variables in newly diagnosed lung cancer adult patients for the integral evaluation and possible prognostic of them.MethodsThis Pilot study was retrospective and cross-sectional and 23 patients aged 53–82 years participated in it. The electrical resistance and capacitive electrical reactance were measured with the Bodystat Quadscan® 4000 analyzer. The electrical impedance modulus and the phase angle were calculated. The serum concentrations of epidermal growth factor, CYFRA21-1 and CA 72–4 were quantified. Correlations/associations among variables and the principal component analysis were suggested.ResultsThe majority of patients had tumor markers, electrical resistance and the phase angle in their respective normal ranges. The capacitive electrical resistance was below its normal range. Minimum, low and moderate grades of linear correlation/association prevailed among studied variables. The principal components I and II were interpreted as prognosis and body energetic reserve of the patient, respectively.ConclusionsIt is concluded that the clinical, bioelectrical and functional variables allow the integral analysis and possible prognosis of newly diagnosed lung cancer adult patients. The decrease of the capacitive electrical reactance is the most influence to the loss of the body energetic reserve that leads to alterations of the overall health, tiredness and decrease of weight and body mass index of these patients.

Widespread cell stress and mitochondrial dysfunction occur in patients with early Alzheimer's disease.

Cell stress and impaired oxidative phosphorylation are central to mechanisms of synaptic loss and neurodegeneration in the cellular pathology of Alzheimer's disease (AD). In this study, we quantified the in vivo expression of the endoplasmic reticulum stress marker, sigma 1 receptor (S1R), using [11C]SA4503 positron emission tomography (PET), the mitochondrial complex I (MC1) with [18F]BCPP-EF, and the presynaptic vesicular protein SV2A with [11C]UCB-J in 12 patients with early AD and in 16 cognitively normal controls. We integrated these molecular measures with assessments of regional brain volumes and cerebral blood flow (CBF) measured with magnetic resonance imaging arterial spin labeling. Eight patients with AD were followed longitudinally to estimate the rate of change of the physiological and structural pathology markers with disease progression. The patients showed widespread increases in S1R (≤ 27%) and regional reduction in MC1 (≥ -28%) and SV2A (≥ -25%) radioligand binding, brain volume (≥ -23%), and CBF (≥ -26%). [18F]BCPP-EF PET MC1 binding (≥ -12%) and brain volumes (≥ -5%) showed progressive reductions over 12 to 18 months, suggesting that they both could be used as pharmacodynamic indicators in early-stage therapeutics trials. Associations of reduced MC1 and SV2A and increased S1R radioligand binding with reduced cognitive performance in AD, although exploratory, suggested a loss of metabolic functional reserve with disease. Our study thus provides in vivo evidence for widespread, clinically relevant cellular stress and bioenergetic abnormalities in early AD.

The association of a frailty index from laboratory tests and vital signs with clinical outcomes in hospitalized older adults.

Frailty, a state of vulnerability to stressors resulting from loss of physiological reserve due to multisystemic dysfunction, is common among hospitalized older adults. Hospital clinicians need objective and practical instruments that identify older adults with frailty. The FI-LAB is based on laboratory values and vital signs and may capture biological changes of frailty that predispose hospitalized older adults to complications. The study's aim was to assess the association of the FI-LAB versus VA-FI with hospital and post-hospital clinical outcomes in older adults. Retrospective cohort study was conducted on Veterans aged ≥60 admitted to a VA hospital. We identified acute hospitalizations January 2011-December-2014 with 1-year follow-up. A 31-item FI-LAB was created from blood laboratory tests and vital signs collected within the first 48 h of admission and scores were categorized as low (<0.25), moderate (0.25-0.40), and high (>0.40). For each FI-LAB group, we obtained odds ratio (OR) and confidence intervals (CI) for hospital and post-hospital outcomes using multivariate binomial logistic regression. Additionally, we calculated hazard ratios (HR) and CI for all-cause in-hospital mortality comparing the high and moderate FI-LAB group with the low group. Patients were 1407 Veterans, mean age 72.7 (SD=9.0), 67.8% Caucasian, 96.1% males, 47.0% (n=661), 41.0% (n=577), and 12.0% (n=169) were in the low, moderate, and high FI-LAB groups, respectively. Moderate and high scores were associated with prolonged LOS, OR:1.62 (95% CI:1.29-2.03); and 3.36 (95% CI:2.27-4.99), ICU admission, OR:1.40 (95% CI:1.03-1.90); and OR:2.00 (95% CI:1.33-3.02), nursing home placement OR:2.36 (95% CI:1.26-4.44); and 5.99 (95% CI:2.83-12.70), 30-day readmissions OR:1.74 (95% CI:1.20-2.52); and 2.20 (95% CI:1.30-3.74), 30-day mortality OR: 2.51 (95% CI:1.01-6.23); and 8.97 (95% CI:3.42-23.53), 6-month mortality OR:3.00 (95% CI:1.90-4.74); and 6.16 (95% CI:3.55-10.71), and 1-year mortality OR: 2.66 (95% CI:1.87-3.79); and 4.76 (95% CI:3.00-7.54) respectively. The high FI-LAB group showed higher risk of in-hospital mortality, HR:18.17 (95% CI:4.01-80.52) with an area-under-the-curve of 0.843 (95% CI:0.75-0.93). High and moderate FI-LAB scores were associated with worse in-hospital and post-hospital outcomes. The FI-LAB may identify hospitalized older patients with frailty at higher risk and assist clinicians in implementing strategies to improve outcomes.

Associations between frailty trajectories and cardiovascular, renal, and mortality outcomes in chronic kidney disease.

BackgroundFrailty is characterized by the loss of biological reserves and vulnerability to adverse outcomes. In individuals with chronic kidney disease (CKD), numerous pathophysiological factors may be responsible for frailty development including inflammation, physical inactivity, reduced energy intake, and metabolic acidosis. Given that both CKD and frailty incur a significant healthcare burden, it is important to understand the relationship of CKD and frailty in real‐world routine clinical practice, and how simple frailty assessment methods (e.g. frailty indexes) may be useful. We investigated the risk of frailty development in CKD and the impact of frailty status on mortality and end‐stage kidney disease (ESKD).MethodsA retrospective cohort study using primary care records from the Clinical Practice Research Datalink linked to Hospital Episode Statistics and the UK Office for National Statistics was undertaken in 819 893 participants aged ≥40 years, of which 140 674 had CKD. Frailty was defined using an electronic frailty index, generated electronically from primary care records. Cox proportional hazard and flexible parametric survival models were used to investigate the risk of developing frailty and the effect of frailty on risk of all‐cause and cardiovascular mortality, and ESKD.ResultsThe mean age of those with CKD was 77.5 (SD 9.7) years [61.0 (SD 12.1) years in no‐CKD group]; 62.0% of the CKD group were female (compared with 53.3% in no‐CKD group). The mean estimated glomerular filtration rate of those with CKD was 46.1 (SD 9.9) mL/min/1.73 m2. The majority of those with CKD (75.3%) were frail [vs. 45.4% in those without CKD (no‐CKD)]. Over 3 years (median), 69.5% of those with CKD developed frailty. Compared with no‐CKD, those with CKD had increased rates of developing mild (hazard ratio: 1.02; 95% confidence interval: 1.01–1.04), moderate (1.30; 1.26–1.34), and severe (1.50; 1.37–1.65) frailty. Mild (1.22; 1.19–1.24), moderate (1.60; 1.56–1.63), and severe (2.16; 2.11–2.22) frailty was associated with increased rates of all‐cause and cardiovascular‐related mortality (mild 1.35; 1.31–1.39; moderate 1.96; 1.90–2.02; and severe 2.91; 2.81–3.02). All stages of frailty significantly increased ESKD rates.ConclusionsFrailty is highly prevalent and associated with adverse outcomes in people with CKD, including mortality and risk of ESKD. Preventative interventions should be initiated to mitigate the development of frailty. The use of a simple frailty index, generated electronically from health records, can predict outcomes and may aid prioritization for management of people with frailty.

P-453 No major changes in ovarian function after unilateral ovariectomy in the context of ovarian tissue cryopreservation in girls with Turner syndrome

Abstract Study question What is the impact of unilateral ovariectomy on the ovarian function in girls with Turner syndrome (TS) undergoing ovarian tissue cryopreservation (OTC)? Summary answer In most girls with TS, ovarian markers remained stable up to three years after unilateral ovariectomy. What is known already Girls with TS have a complete or partial loss of one of the sex-chromosomes causing premature ovarian insufficiency which reduces the chances of a spontaneous pregnancy. OTC may be an option to preserve fertility at an early age to increase the chance on genetic offspring. However, this requires a unilateral ovariectomy for young girls with TS who are already subjected to an accelerated loss of ovarian reserve. Previous research in women without TS undergoing a unilateral ovariectomy has shown that the remaining ovary compensate for the function of the removed ovary with no effect on pubertal development and fertility outcome. Study design, size, duration This is a descriptive study of 28 girls with TS (age 5-19 years). Girls were monitored for up to three years after unilateral ovariectomy on pubertal development, and level of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrogen, Anti-Mullerian hormone (AMH) and inhibin B. Participants/materials, setting, methods The cohort was recruited from girls with TS undergoing OTC as part of the ongoing TurnerFertility study at a university medical centre. Follicles were found in the ovarian cortex fragments in 28 of the 86 cases. These cases were considered to have functional ovaries and were included in the study. Main results and the role of chance Follow-up data are not yet available for three girls because they had surgery only three months ago. Of the other 25 girls, two girls had a monosomic karyotype (45,X), fourteen were mosaic (45,X/46,XX), four had a mosaic with triple X-chromosome (45,X/47,XXX) and five girls had structural aberrations of the X chromosome. Ten girls were prepubertal at time of unilateral ovariectomy, twelve girls had a spontaneous thelarche and three girl had induced puberty. After unilateral ovariectomy, one of the 10 prepubertal girls entered puberty spontaneously and one of the prepubertal girls needed puberty induction. It is still unknown what the impact of a unilateral ovariectomy will be on the pubertal development of the other girls, due to their young age but AMH levels remained stable. 8/12 girls with spontaneous thelarche maintained a measurable AMH and FSH &amp;lt;20 IE/L during the median follow-up of 20 months (IQR 13-30). 4/12 girls with spontaneous thelarche before OTC needed hormone supplementation because of signs of premature ovarian insufficiency, e.g. irregular menstruations (n = 2), flushes (n = 1) and high FSH (84 IE/L; n = 1). However, these girls had unfavourable hormonal parameters before unilateral ovariectomy (e.g. AMH &amp;lt; 0.5 ug/L or FSH &amp;gt; 20 IE/L). Limitations, reasons for caution These results should be interpreted with caution because of the highly heterogeneous population of girls with TS. Moreover, the results should ideally be compared with age- and karyotype-matched controls to determine the natural course of ovarian function of girls with TS. Wider implications of the findings This cohort will be monitored for a longer period of time to observe the consequences on pubertal development, need for hormone supplementation, and eventually fertility outcome. If OTC becomes part of routine care for girls with TS, our results will be of great value in the counselling for future parenthood. Trial registration number NCT03381300

P-582 Novel anti-Mullerian hormone receptor 2 binding peptide (AMHR2BP) modulates murine ovarian follicle cell proliferation and oocyte function in vivo

Abstract Study question We sought to investigate whether the inhibitory effects of the novel peptide AMHR2BP on ovarian cortex gene transcription are translated into decreased protein synthesis. Summary answer AMHR2BP, like recombinant AMH, profoundly inhibited protein transcription of FSH-R, Ki67, BMP15 and GDF9 in ovarian cortex, confirming its role in inhibition of ovarian function. What is known already We previously showed how anti-Müllerian hormone (AMH) inhibited hormone production, and ovarian cortex follicle development in in vitro, and in vivo, ovarian cortex, and in luteinized granulosa cells. We then developed an AMH receptor 2 binding peptide (AMHR2BP) that could mimic AMH functions and parallel-tested it with AMH. Using histology and real-time RT-PCR we showed that, similarly to AMH, AMHR2BP inhibited granulosa cells replication and function and preserved ovarian follicle number by minimizing the progression of follicular development throughout its administration, in a mouse model. In addition, AMHR2BP decreased follicle hormone production, cell replication and apoptosis, and inhibited oocyte function. Study design, size, duration This was a translational study where 24 18-weeks old C57BL female mice were equally divided and assigned to four treatments: Baseline (euthanized just prior to the experiment), AMHR2BP (AMHR2-BP, 50 µg /day), rAMH (recombinant AMH, 1.8 µg /day), and placebo group (normal saline), administered via intraperitoneal pumps. Mice were euthanized 3 weeks after pump placement and the ovaries were explanted for histology, real-time RT-PCR and ELISA testing. Histology and real-time RT-PCR results were previously reported. Participants/materials, setting, methods We performed ELISA on mouse ovary lysates to quantify protein concentration of FSH receptor (FSH-R), Ki67 (stimulates cell proliferation), and the two oocyte-derived hormones that stimulate mitotic proliferation in granulosa cells, BMP15 and GDF9. Both, BMP15 and GDF9 act in an additive manner and have a critical role in granulosa and theca cell growth, as well as in differentiation and maturation of the oocyte. We used Kruskall-Wallis for comparison of medians (SPSS v25; p &amp;lt; 0.05). Main results and the role of chance Compared with the Baseline and Placebo groups, AMHR2BP and rAMH administration caused a significant decrease in concentration of all the parameters under investigation, indicating inhibition of cellular function. Specifically, a decreased FSH-R indicated loss of pituitary stimulation of follicular growth; a decreased Ki67 showed inhibition of cellular replication; a decrease in BMP15 and GDF9 indicated stalling of granulosa and theca cell growth, as well as of oocyte differentiation and maturation. The table reports the individual groups’ data. Limitations, reasons for caution With this experiment we cannot prove a direct effect on the oocyte or the granulosa cells, as they were not individually tested. Our previous gene expression study on granulosa cells proved a direct inhibitory effect of AMHR2BP as well as recombinant AMH on granulosa cells. Wider implications of the findings We confirmed AMHR2BP’s overall inhibitory effect on ovarian function and development, for the duration of its administration. Combined with our previous findings of direct inhibition of in vitro and in vivo follicular development, we conclude that AMHR2BP could be used to inhibit age-linked loss of ovarian follicle reserve. Trial registration number Cleveland Clinic

Targeted Deletion of Mitofusin 1 and Mitofusin 2 Causes Female Infertility and Loss of Follicular Reserve.

Mitochondria are dynamic organelles that regulate their size, shape, and morphology through mechanisms called fusion and fission, to continually adapt themselves to their bioenergetic environment. These mechanisms play a critical role to maintain the mitochondrial function under metabolic and environmental stress. Mitofusin 1 (MFN1) and mitofusin 2 (MFN2) are transmembrane GTPases that regulate mitochondrial fusion mechanism and are required for the maintenance of cellular homeostasis. In this study, we aimed to determine the role of mitofusins in female reproductive competence and senescence using a mouse model with oocyte-specific double deletion of Mfn1 and Mfn2, eliminating the potential functional redundancy of these two proteins. Oocyte-specific targeted double deletion of Mfn1 and Mfn2 in mice resulted in female infertility associated with impaired follicular development and oocyte maturation. It also resulted in altered mitochondrial dynamics and mitochondrial dysfunction. Lack of Mfn1 and Mfn2 in oocytes resulted in accelerated follicular depletion and impaired oocyte quality which are consistent with phenotype of reproductive aging.

Monitoring the spontaneous combustion zone of a rock-coal massif using the ground-penetrating radar method

Introduction. Endogenous fires are common and one of the most complex types of accidents in the mining industry. The main cause of endogenous fires is oxidation of combustible rock by oxygen. Existing fires significantly complicate mining operations, lead to the loss of coal reserves prepared for excavation, expensive coal-mining equipment, and cause huge economic losses associated with firefighting operations. Fired areas are sources of emissions of gases harmful for breathing into the atmosphere, so the environmental damage is also very significant. Due to the fact that endogenous fires are difficult to predict and forecast, especially in their initial stages, their study is relevant to scientists of the leading research institutes of the mining industry. Research objective is to investigate and analyze the effectiveness of the ground-penetrating radar (GPR) method for diagnosing the spontaneous-combustion zones of the rock-coal massif. Methods of research. In order to assess the effectiveness of the GPR method, field experimental studies on the recognition and localization of underground fires were carried out. In order to determine the informative value of this method, wells were drilled and geological data was compared with the GPR survey results. Results. The site of an active underground fire was visually inspected to predefine the combustion areas; inspection results were presented in the paper. Using the method of GPR sounding and based on the typical anomalous zones location on fire radiograms, the fire sources were diagnosed by depth and on the plan. Boreholes were drilled to study the lithological structure of the rock mass. Additional GPR sounding was aimed at defining the width of the fire in plan more precisely. Conclusions. The GPR method makes it possible to obtain on-line data on the location of coal massif spontaneous-combustion zones and their sizes. This technology contributes to timely measures for preventing the development of underground fires in the territories of mines and open pits surface plants.