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Sirtuin 5 (SIRT5) is a protein lysine deacylase enzyme that regulates diverse biology by hydrolyzing -N-carboxyacyllysine posttranslational modifications in the cell. Inhibition of SIRT5 has been linked to potential treatment of several cancers but potent compounds with activity in cells have been lacking. Here we developed mechanism-based inhibitors that incorporate isosteres of a carboxylic acid residue that is important for high-affinity binding to the enzyme active site. By masking of the tetrazole moiety of the most potent candidate from our initial SAR study, we achieved potent and cytoselective growth inhibition for the treatment of SIRT5-dependent leukemic cancer cell lines in culture. Thus, we provide an efficient, cellularly active small molecule that targets SIRT5, which can help elucidate its function and potential as a future drug target. This work shows that masked biosisosteres of carboxylic acids are viable chemical motifs for the development of inhibitors that target mitochondrial enzymes, which may have applications beyond the sirtuin field.

Execution of automatically generated programsfor accurate robotic machining requires the generated trajectories to be not only accurate with respect to the workpiece, but also that the trajectories are continuous differentiable(C1) while avoiding unnecessary large curvatures leading tolarge accelerations that could compromise machining qualityor speed. A widely used work piece representation is 3Dtriangle meshes as they can be easily generated in any CADrepresentations and from surface scans, and they are also verysuitable for robotics applications. However, they lack the C1property across the triangle edges.In this paper, a new method for generating C1 surfacesbased on 3D triangle meshes is presented. It will be shownby an example that the method is as good as existing methodswith respect to the accuracy of the generated surface, and thatthe problem with large curvatures is much smaller than forexisting methods. Moreover, the difficult input specification ofderivatives at the vertices is avoided with this method.

A comercialização de organismos aquáticos ornamentais se destaca entre os vários segmentos do mercado Pet no Brasil. Dentre as diversas espécies utilizadas para a aquariofilia, as carpas coloridas, conhecidas como Koi ou Nishikigoi (Cyprinus Carpio L.), representam a principal espécie comercializada no país. Neste contexto, o presente estudo realizou a análise da viabilidade econômica da produção de carpa Nishikigoi em uma piscicultura comercial instalada na região metropolitana de São Paulo que comercializa animais para o mercado Pet brasileiro de peixes ornamentais. Avaliaram-se três hectares de lâmina de água durante dez ciclos de produção por ano. Neste período, foram obtidos os custos totais de produção (CT) e os custos operacionais efetivos (COE) e custos operacionais totais (COT), acrescidos dos custos fixos para operacionalização deste agronegócio. Indicadores econômicos foram aplicados para avaliar a viabilidade de investimento no negócio por meio da taxa interna de retorno (TIR), valor presente líquido (VPL), período de retorno do capital (PRC) e relação custo-benefício do investimento (RCB). A projeção de investimento inicial foi de ̴2.3 milhões de reais. Os indicadores econômicos de viabilidade mais expressivos foram obtidos pelo TIR de 10.41% ao ano e VPL de aproximadamente 1.6 milhões de reais, considerando o fluxo líquido de caixa para o período de dez anos. O período de retorno do capital investido poderá ser alcançado em 7.15 anos com um RBC em 1.68 reais. Dessa maneira, o cenário estudado demostrou a viabilidade de investir neste agronegócio sendo um empreendimento promissor do setor da aquicultura.

Objective It is generally accepted that the incidence of birth defects in spontaneously conceived children ranges between 2.0-4.0%. However, several studies have shown that babies born after assisted reproductive technology (ART) procedures tend to present more congenital malformations than naturally conceived children, with 6.5% of the children born after intracytoplasmic sperm injection (ICSI) presenting birth defects. The use of high magnification sperm selection before ICSI was introduced in the early 2000s to allow the identification of spermatozoa with low risk of sperm DNA damage. Intracytoplasmic morphologically selected sperm injection (IMSI) is expected to change the incidence of congenital malformations, although data on the incidence of birth defects in children conceived after IMSI are still scarce. Methods A systematic review based on searches performed in electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane Central Register of Controlled Trials) including articles published by February 2021 was conducted to identify trials comparing the neonatal outcomes of ICSI and IMSI. The outcome measured was the rate of birth defects in children born after ICSI or IMSI. Three trials were included as targets for data extraction and meta-analysis. Results Our meta-analysis included 3907 children conceived after IMSI (1280) or ICSI (2627). The incidence of birth defects was statistically different, with 2.5% (32/1280) in IMSI and 4.5% (119/2627) in ICSI (RR=0.59; 95% CI=0.40-0.87; p=0.007). The results demonstrated that IMSI decreased the incidence of structural defects compared to ICSI - 2.2% (18/830) vs. 3.8% (78/2049) - in a statistically significant manner (RR=0.58; 95%CI=0.35-0.96; p=0.04). No significant difference was observed in chromosomal abnormalities (Trisomy 13; 18; 21 and Triple X) between children conceived after IMSI (8/830) or ICSI (19/2049) (RR=1.07; 95%CI=0.47-2.43; p=0.87). Conclusions IMSI seems to be an effective tool at reducing the incidence of structural defects compared to ICSI. However, IMSI does not change the incidence of chromosomal abnormalities.

We sought to determine whether gravity-induced changes in intracranial pressure influence cerebral blood flow regulation. Accordingly, nine young healthy men were studied while supine (0°) and during mild changes in hydrostatic pressure induced by head-up tilt at +20° and +10° (HUT+20 and HUT+10) and head-down tilt at -20° and -10° (HDT-20, HDT-10). Blood flows were measured in the internal and external carotid and vertebral arteries (ICA, ECA, and VA). Intraocular pressure (IOP) was measured as an indicator of hydrostatic changes in intracranial pressure. A posture change from HUT+20 to HDT-20 increased IOP by +5.1 ± 1.9 mmHg (

The COVID‐19 pandemic has produced critical shortages of ventilators worldwide. There is an unmet need for rapidly deployable, emergency‐use ventilators with sufficient functionality to manage COVID‐19 patients with severe Acute Respiratory Distress Syndrome. Here we show the development and validation of a simple, portable, and low‐cost ventilator that may be rapidly manufactured with minimal susceptibility to supply chain disruptions. This single‐mode continuous, mandatory, closed‐loop, pressure‐controlled, time‐terminated emergency ventilator offers robust safety and functionality absent in existing solutions to the ventilator shortage. Validated using certified test lungs over a wide range of compliances, pressures, volumes and resistances to meet U.S. Food and Drug Administration standards of safety and efficacy, an Emergency Use Authorization is in review for this system. This emergency ventilator could eliminate controversial ventilator rationing or splitting to serve multiple patients. All design and validation information is provided to facilitate ventilator production even in resource‐limited settings.

When 49 people were gunned down in an Orlando nightclub in 2016, journalists from all over Central Florida went toward the nightclub, not away from it. This study explores the lived experience of 18 journalists who covered the Pulse nightclub shooting. Participants came from a variety of news outlets—print, television, and radio—and from a variety of positions—reporters, photographers, and editors. Participants described the chaotic environment and the ethical issues they faced. This paper sheds light on how journalists handle situations like the Pulse shooting and the need to monitor the mental health of those who were on the frontlines covering it.

Objective To assess the relationship between human blastocyst chromosomal ploidy established by niPGT-A and increasing age. Methods This is a prospective multicenter study carried out by ten assisted reproduction centers after their embryologists acquired training and validated their results with the previous use of niPGT-A. A total of 94 couples with indication for niPGT-A due to increase maternal age, male factor, repeated implantation failures, recurrent abortion or because they requested niPGT-A were included in this study. The couples had no karyotype abnormalities. After ICSI, the embryos were cultured until blastocyst stage using one or two step culture systems, single or sequential media respectively, at 37°C in an atmosphere of 6-7% CO2 and 5-20% O2 incubators. On day 3, we re-evaluated cleavage embryos to complete cumulus cells removal. The embryos were then cultured in individual well, with 20µl of medium under oil until they reached blastocyst stage. The blastocysts were vitrified and stored in liquid nitrogen. After that, the spent blastocyst culture medium (20µl) was transferred to a PCR tube and sent for analysis in the genetic laboratory, where it was stored at -80°C until sequencing. A total of 243 samples of spent blastocyst culture medium were collected on the 5th/6th day. Cell-free DNA secreted on culture medium was amplified using NICS Sample Preparation Kit (Yikon Genomics), based on the MALBAC technology. After whole genome amplification, the DNA was measured using a Qubit 2.0 fluorometer and subjected to next generation sequencing (NGS) using Illumina MiSeq® platform. The data were analyzed using the ChromGo® software (Yikon Genomics). Results The mean age of the patients was 38±4.08 years with an interval of 20-44 years. The euploid was diagnosed in 36.4% (80/220) of cases, aneuploidy in 31.3% (69/220), and mosaicism in 32.3% (71/220; with ≥60% aneuploidy) of blastocysts. Mosaic values ranged from 29.8% to 33.8% in different age groups. Individually, the most frequent chromosomal abnormality was XXY (Klinefelter Syndrome) occurring in 18 cases, followed by chromosome 21 (trisomy/monosomy) in 8 cases. The niPGT-A data showed a ≥60% incidence of aneuploid cells in all cases of chromosomal mosaicism (n=71). Conclusion A high degree of mosaicism with aneuploidy cells was detected, and some hypotheses were suggested for this data (niPGT-A sensitivity in detecting the self-correction of chromosomal abnormalities phenomenon). However, it did not vary remarkably with age. On the other hand, euploidy levels had a negative correlation with age and aneuploidy levels had a positive relationship. This is the first report in the literature to relate chromosomal ploidy in blastocysts using niPGT-A and increasing patient age.

Recently, a new technology known as the Noninvasive Preimplantation Genetic Testing for Aneuploidy (niPGT-A) emerged, using cell-free DNA present in the spent culture media of human blastocysts. Unlike PGT-A, in which only trophectoderm cells are used, niPGT-A reflects the ploidy state of these cells and internal cell mass, suggesting that this new technology may be less prone to error, being more reliable than the invasive test. The aim of the present study was to report the first occurrence of childbirth following niPGT-A in Brazil.

KEY POINTS: During long‐term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial hypertension. Weightlessness prevents the normal cerebral volume and pressure ‘unloading’ associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology. By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, we simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments. Application of incremental LBNP demonstrated a non‐linear dose–response curve, suggesting 20 mmHg LBNP as the optimal level for reducing pressure in the brain without impairing cerebral perfusion pressure. This non‐invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as having treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension. ABSTRACT: Patients with elevated intracranial pressure (ICP) exhibit neuro‐ocular symptoms including headache, papilloedema and loss of vision. Some of these symptoms are also present in astronauts during and after prolonged space‐flight where lack of gravitational stress prevents daily lowering of ICP associated with upright posture. Lower body negative pressure (LBNP) simulates the effects of gravity by displacing fluid caudally and we hypothesized that LBNP would lower ICP without compromising cerebral perfusion. Ten cerebrally intact volunteers were included: six ambulatory neurosurgical patients with parenchymal ICP‐sensors and four former cancer patients with Ommaya‐reservoirs to the frontal horn of a lateral ventricle. We applied LBNP while recording ICP and blood pressure while supine, and during simulated intracranial hypertension by 15° head‐down tilt. LBNP from 0 to 50 mmHg at increments of 10 mmHg lowered ICP in a non‐linear dose‐dependent fashion; when supine (n = 10), ICP was decreased from 15 ± 2 mmHg to 14 ± 4, 12 ± 5, 11 ± 4, 10 ± 3 and 9 ± 4 mmHg, respectively (P

INTRODUCTION: Chronic kidney disease (CKD) is a global health concern, but the current treatments only slow down the progression. Thus an improved understanding of the pathogenesis and novel treatments of CKD are needed. The nephrotoxic nephritis (NTN) model has the potential to study the pathogenesis of CKD as it resembles human CKD. The classical treatments with angiotensin II receptor blocker (ARB) or the angiotensin-converting enzyme inhibitor (ACE I) have shown a clinical effect in CKD.METHODS: We characterized the disease development in the NTN model over 11 weeks by investigating functional and histopathological changes. We tested doses of 15 and 30 mg/kg/day enalapril and losartan in the NTN model in order to investigate the effect of inhibiting the renin-angiotensin-system (RAS).RESULTS: The NTN model displayed albuminuria peaking on days 6-7, mesangial expansion (ME), renal fibrosis, inflammation and iron accumulation peaking on day 42. However, albuminuria, ME, renal fibrosis and inflammation were still significantly present on day 77, suggesting that the NTN model is useful for studying both the acute and chronic disease phases. Enalapril and losartan significantly enhanced the glomerular filtration rate (GFR) and decreased albuminuria, ME, renal fibrosis and inflammation of NTN-induced kidney disease in mice.CONCLUSIONS: This is the first study showing a comprehensive pathological description of the chronic features of the murine NTN model and that inhibiting the RAS pathway show a significant effect on functional and morphological parameters.

High-intensity interval exercise (HIIE) improves cerebral executive function (EF), but the improvement in EF is attenuated after repeated HIIE, perhaps because of lower lactate availability for the brain. This investigation examined whether improved EF after exercise relates to brain lactate uptake. Fourteen healthy, male subjects performed 2 HIIE protocols separated by 60 min of rest. Blood samples were obtained from the right internal jugular venous bulb and from the brachial artery to determine arterial-venous differences across the brain for lactate (a-v difflactate), glucose (a-v diffglucose), oxygen (a-v diffoxygen), and brain-derived neurotrophic factor (BDNF; a-v diffBDNF). EF was evaluated by the color-word Stroop task. The first HIIE improved EF for 40 min, whereas the second HIIE improved EF only immediately after exercise. The a-v diffglucose was unchanged, whereas the a-v diffBDNF increased similarly after both HIIEs, and the a-v difflactate increased, but the increase was attenuated after the second HIIE, compared with the first HIIE ( P < 0.05). The EF after HIIE correlated with the a-v difflactate ( r2 = 0.62; P < 0.01). We propose that attenuated improvement in EF after repeated HIIE relates to reduced cerebral lactate metabolism and is, thereby, linked to systemic metabolism as an example of the lactate shuttle mechanism.-Hashimoto, T., Tsukamoto, H., Takenaka, S., Olesen, N. D., Petersen, L. G., Sorensen, H., Nielsen, H. B., Secher, N. H., Ogoh, S. Maintained exercise-enhanced brain executive function related to cerebral lactate metabolism in men.

OBJECTIVE This study aimed to evaluate the effects of male age on sperm DNA damage. METHODS This cross-sectional study included semen samples collected from 2,178 men seen at an infertility clinic. For DNA integrity analysis, the proportions of spermatozoa showing DNA fragmentation (TUNEL assay), abnormal chromatin packaging/underprotamination (chromomycin A3), abnormal mitochondrial membrane potential (MMP/MitoTracker Green), and apoptosis (annexin V) were recorded. For group comparisons, enrolled subjects were divided into three groups based on their ages: ≤35 years; 36-44 years; and ≥45 years. The associations between age and sperm parameters were assessed using Spearman's rank correlation coefficient. RESULTS Although aging did not affect sperm apoptosis (p>.05), sperm DNA fragmentation and MMP deteriorated significantly with age (p

The nautilid Eutrephoceras dekayi (Morton 1834) is relatively abundant in the lower Maastrichtian (Upper Cretaceous) Pierre Shale of east-central Montana. We analysed the morphology, size frequency distribution, and isotope composition of a large collection of 220 well-preserved specimens including hatchlings, juveniles and adults. The newly hatched shell is approximately 14 mm in diameter with a body chamber one-third whorl in angular length terminating in the nepionic constriction. Internally, the embryonic shell contains five septa. Juveniles are abundant and comprise two-thirds of the sample whereas sub-adults, defined by the incipient flattening of the venter, are rare. Adults comprise approximately one-third of the sample and average 100 mm in diameter. The co-occurrence of newly hatched shells, small juveniles and adults suggests that the eggs were laid in the same area in which the hatchlings developed. Based on the excellent preservation of the juveniles, we conclude that they did not float into the area after death, but lived in the region, implying that this area served as a nursery for young animals. The calculated temperatures of the embryonic shells are similar to those of the post-embryonic shells and generally range from 16 to 18 °C. Upon hatching, the nautilids probably followed a demersal mode of life and lived in well-oxygenated water ≤50 m deep. An examination of lethal injuries (puncture holes) suggests that all ontogenetic stages were equally vulnerable to predation. The proximity of the site to the Sheridan Delta suggests that the specimens were smothered by sudden pulses of sediment transported into the area by major storms.

Objectives/hypothesis Our objective was to describe epistaxis onset and severity in pediatric hereditary hemorrhagic telangiectasia (HHT) patients and study the cumulative incidence of epistaxis by age of onset within each genetic subtype. Study design Retrospective cohort chart review. Methods Charts were reviewed of patients age 0 to 18 years with a clinical or genetic diagnosis of HHT who were evaluated at a tertiary multidisciplinary HHT clinic from January 2010 to June 2016. The epistaxis severity score (ESS), a validated tool for assessing epistaxis severity, was used to assess epistaxis. Statistical analyses were conducted on the full HHT cohort as well as subgroups stratified by the HHT causative gene (HHT1 = ENG and HHT2 = ACVRL1). Results Sixty-nine pediatric subjects were identified; 60 had HHT confirmed by genetic testing, and nine (from families with known mutations) met published clinical diagnostic criteria alone. Fifty-nine (85%) had onset of epistaxis. The median age of onset of epistaxis was 5 years (interquartile range [IQR]: 2-9 years). The median ESS for the entire cohort was 1.6 (IQR: 0-2.6). The median ESS was higher in HHT1 versus HHT2 (2.3 vs. 1.1, P = .002), and age of epistaxis onset was earlier in HHT1 (3 vs. 5 years, P = .03). Sex and age were not associated with ESS. Conclusions Epistaxis may present early in HHT, but is typically mild in the pediatric period. Severity in the pediatric population is worse in patients with HHT1. By recognizing the significance of even mild, infrequent epistaxis in a child with a family history of HHT, and understanding that not all HHT patients have epistaxis during childhood, community providers and otolaryngologist can assist in the early detection of HHT. Level of evidence 4 Laryngoscope, 128:1714-1719, 2018.

Key Points Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth. Gravity has a profound effect on fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure. This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts. Abstract Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure (ICP). This syndrome is considered the most mission-critical medical problem identified in the past decade of manned spaceflight. We recruited five men and three women who had an Ommaya reservoir inserted for the delivery of prophylactic CNS chemotherapy, but were free of their malignant disease for at least 1 year. ICP was assessed by placing a fluid-filled 25 gauge butterfly needle into the Ommaya reservoir. Subjects were studied in the upright and supine position, during acute zero gravity (parabolic flight) and prolonged simulated microgravity (6 deg head-down tilt bedrest). ICP was lower when seated in the 90 deg upright posture compared to lying supine (seated, 4 ± 1 vs. supine, 15 ± 2 mmHg). Whilst lying in the supine posture, central venous pressure (supine, 7 ± 3 vs. microgravity, 4 ± 2 mmHg) and ICP (supine, 17 ± 2 vs. microgravity, 13 ± 2 mmHg) were reduced in acute zero gravity, although not to the levels observed in the 90 deg seated upright posture on Earth. Prolonged periods of simulated microgravity did not cause progressive elevations in ICP (supine, 15 ± 2 vs. 24 h head-down tilt, 15 ± 4 mmHg). Complete removal of gravity does not pathologically elevate ICP but does prevent the normal lowering of ICP when upright. These findings suggest the human brain is protected by the daily circadian cycles in regional ICPs, without which pathology may occur.

Anaerobic hydrolysis in activated return sludge was investigated in laboratory scale experiments to find if intermittent aeration would accelerate anaerobic hydrolysis rates compared to anaerobic hydrolysis rates under strict anaerobic conditions. The intermittent reactors were set up in a 240 h experiment with intermittent aeration (3 h:3 h) in a period of 24 h followed by a subsequent anaerobic period of 24 h in a cycle of 48 h which was repeated five times during the experiment. The anaerobic reactors were kept under strict anaerobic conditions in the same period (240 h). Two methods for calculating hydrolysis rates based on soluble chemical oxygen demand were compared. Two-way analysis of variance with the Bonferroni post-test was performed in order to register any significant difference between reactors with intermittent aeration and strictly anaerobic conditions respectively. The experiment demonstrated a statistically significant difference in favor of the reactors with intermittent aeration showing a tendency towards accelerated anaerobic hydrolysis rates due to application of intermittent aeration. The conclusion of the work is thus that intermittent aeration applied in the activated return sludge process can improve the treatment capacity further in full scale applications.

We tested the hypotheses that: (1) carotid body size can be measured by computed tomographic angiography (CTA) with high inter-observer agreement, and (2) patients with sleep apnea exhibit larger carotid bodies than those without sleep apnea. A chart review was conducted from patients who underwent neck CTA and polysomnography at the Mayo Clinic between January 2000 and February 2015. Widest axial measurements of the carotid bodies, performed independently by two radiologists, were possible in 81% of patients. Intra-class correlation coefficients ranged from 0.93 to 0.95 (Right carotid body: 0.93; Left: 0.94; Average: 0.95). Widest axial measurements of the carotid bodies were greater in patients with sleep apnea (n=32) compared to controls (n=46, P-value range 0.02-0.04). After adjusting for age, no differences in carotid body size were observed between the patient groups (P-value range 0.45-0.59). We conclude carotid body size can be detected by CTA with high inter-observer agreement; however, carotid body size is not increased in patients with sleep apnea.

Objective The present meta-analysis aimed to evaluate whether the freeze-all strategy (Freeze/All-ET) could bring about improvements in the clinical assisted reproductive technique (ART) outcomes when compared with the fresh embryo transfer strategy (Fresh-ET) in patients undergoing an ART cycle in accordance with the mean number of oocytes collected. Methods A systematic review based on electronic searches in databases (PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane Central Register of Controlled Trials) was carried out to identify randomized controlled trails (RCTs) comparing ART outcomes between fresh-embryo transfers versus elective frozen-embryo transfers up to February of 2017. Four reviewers independently evaluated abstracts, validity assessment and data extraction. Odds Ratio (OR) values with a 95% confidence interval (CI), and heterogeneity were evaluated. Results Five RCTs were included as targets for data extraction and meta-analysis purposes. The results of this meta-analysis were divided into two parts (Freeze/All-ET versus Fresh-ET): Part I- All trials in which the mean number of collected oocytes was >12 and 12 and

Objective The aim of this study was to evaluate the influence of different periods of abstinence on conventional semen parameters as well as functional parameters in human semen, including mitochondrial function, chromatin packing and sperm DNA fragmentation. Methods We recruited a cohort of 2,458 men undergoing infertility investigation. Semen analyses were performed according to WHO guidelines/morphology-motile sperm organelle morphology examination/MSOME. For DNA integrity analysis, the percentages of DNA fragmentation (TUNEL), abnormal chromatin packaging/underprotamination (chromomycin A3/CMA3), abnormal mitochondrial membrane potential (MMP/MitoTracker Green), and apoptosis (annexin-V) were recorded. Associations between the sexual abstinence period and sperm parameters were assessed using Spearman correlation. For group comparisons, the subjects were categorized according to the sexual abstinence period (SAP) into three groups: SAP 5 days. Results The duration of abstinence had a statistically significant positive influence on sperm concentration and volume, the number of leukocytes and a statistically significant negative influence on sperm motility and vitality. The percentages of DNA fragmentation and MMP (mitochondrial damage) worsened with the increased duration of abstinence. The percentage of sperm protamination was statistically significantly increased with abstinence. Conclusion Increase in the sexual abstinence period influences sperm quality. This study reinforces the importance of the duration of ejaculatory abstinence on semen parameter variation. It highlights the deleterious effect of increased abstinence on DNA damage, which is most likely associated with ROS (mitochondrial damage/number of leukocytes). The increase in chromatin packaging can represent a protective feature for DNA.

This study aimed to evaluate if single medium is better than sequential medium at improving ongoing pregnancy rates in patients undergoing assisted reproductive technology (ART) procedures. The data featured in this meta-analysis were extracted from four randomized controlled trials yielded from a systematic search carried out on electronic databases. The primary endpoint was ongoing pregnancy rate. Secondary endpoints included clinical pregnancy and miscarriage rates. The endpoints for ongoing pregnancy rate were also analyzed based on the time at which the embryo transfers were performed: cleavage stage (day 2/3) and/or blastocyst stage (day 5/6). There were no significant differences between single and sequential medium for clinical pregnancy (RR=1.09; 95%CI=0.83-1.44; p=0.53), ongoing pregnancy (RR=1.11; 95%CI=0.87-1.40; p=0.39), or miscarriage rates (RR=0.89; 95%CI=0.44-1.81; p=0.74). No significant difference was found for ongoing pregnancy rate (RR=1.29; 95%CI=0.93-1.78; p=0.12) between single and sequential medium when only trials in which embryos were transferred at the blastocyst stage were included. In conclusion, the choice of embryo culture approach - single or sequential medium - did not affect the ongoing pregnancy rates of patients undergoing ART cycles.

Order picking operations need to efficiently process orders in today’s competitive environment. Previous research generally assumed on even placement of the cross aisles. This research examines the placement of cross aisles in order picking operations and its effect on various storage policies. While previous research has primarily examined cross aisles and storage policies separately, this research looks at them simultaneously. The results showed no difference between even and uneven placement of cross aisles and that within-aisle storage is better than across-aisle and random storage. The results also showed that within-aisle storage provides greater travel distance savings than the use of cross aisles.