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Objectives: The current study assessed the epidemiological trends of semen phenotypes and their association with ethnicity among men seeking fertility treatment in the United Arab Emirates (UAE). Methods: This retrospective study assessed the anthropometric information including age, body mass index (BMI), and nationality, along with semen parameters of men who visited a Fertility Center in Abu Dhabi, UAE between January 2011 and July 2022. To understand the epidemiological trend of semen parameters amongst UAE nationals, propensity score analysis and logistic regression were performed. Thus, the exposure variable of interest is ethnicity, categorized into UAE nationals (Emirati) and Others (minus UAE; Global). Statistical analysis was performed using SPSS, R packages and STATA. Results: In this study, 32,664 samples were collected from 19,482 patients from 113 countries worldwide over a period of 11 years. Most participants made multiple visits, with around 40 % attending at least once. Following covariates adjustment, logistic regression indicated a non-significant increase (4 %) in the prevalence of asthenozoospermia among the UAE population compared to Global. Further modeling adjusted for propensity score and Emirati status suggested that Emiratis were 13 % less likely to have lower total sperm count (TSC) compared to Global (p

Purpose: Many publications address the epidemiology of secondary osteosarcomas following retinoblastoma. Treatment- and outcome-related information is, however, scarce. We used a large cooperative group’s database to study this issue. Patients and methods: The database Cooperative Osteosarcoma Study Group COSS was searched for patients with osteosarcoma following a previous retinoblastoma. Patients were then analyzed for demographic factors, local/systemic treatments received, and outcomes. Results: 28 eligible patients were identified. Median age at retinoblastoma was .5 years, 89% occurred bilaterally. Retinoblastoma-therapy was by surgery in 26/27, radiotherapy in 26/27, chemotherapy in 10/26 (rest unknown). Osteosarcoma was diagnosed after 13.7 (3.1 – 36.1) years, extremities and head/neck affected in 14/28, each. Four/28 patients had primary metastases. Osteosarcoma treatment included chemotherapy in all cases, local therapy surgery in 27/28. Histological response was good in 9/16 evaluable cases. Surgery of all sites was macroscopically complete in 23/27 operated tumors and microscopically complete in 17/26 (1 unknown). Radiotherapy was administered to 3 craniofacial tumors. Median follow-up was 3.5 (.4 – 30.1) years from osteosarcoma diagnosis, 8/28 patients remaining event-free. Altogether, five patients suffered further secondary malignancies. Actuarial overall and event-free survival at 2 and 5 years from osteosarcoma were 73% (standard error: 8%) / 50% (10%) and 47% (10%) / 22% (9%), respectively. Conclusion: This comparatively large cohort of osteosarcomas after retinoblastoma proves that the latter may be treated curatively. While their prognosis is far worse than that of primary osteosarcomas, partly due to a predilection for craniofacial involvement, selected patients may still become long-term survivors with appropriate therapies.

Abstract Background To evaluate patient and tumour characteristics, treatment and their impact on survival in patients with a solitary pulmonary metastasis at first relapse of high‐grade osteosarcoma. Procedure Two‐hundred and nineteen consecutive patients who had achieved a complete surgical remission and then developed a solitary pulmonary metastasis at first recurrence of high‐grade osteosarcoma were retrospectively reviewed. Results Two hundred and three (94.9%) of 214 patients achieved a second complete remission. After a median time from initial diagnosis of osteosarcoma to first relapse of 2.3 years (range, 0.3–18.8 years), actuarial post‐relapse overall survival after 2 and 5 years was 72.0% and 51.2%. Post‐relapse event‐free survival was 39.1% and 31.1%. Median follow‐up time was 3.2 years (range, 0.1–29.4 years). A longer time until first relapse and diagnosis due to imaging were positive prognostic factors in uni‐ and multivariate analyses, as were a second complete surgical remission and, in regard to death, the absence of a subsequent relapse. The use of salvage chemotherapy and radiotherapy were not associated with patient outcomes, nor was the surgical approach (thoracoscopy vs. thoracotomy) nor the exploration (uni‐ vs. bilateral). Conclusion Approximately half of the patients who experience a solitary pulmonary relapse at first recurrence of osteosarcoma remain alive 5 years after this first relapse. Only one third will remain disease‐free. A complete surgical resection of the lesion is essential for long‐term survival while relapse chemotherapy does not seem to improve survival. Innovative therapies are required to improve outcomes.

Monosodium glutamate (MSG), a sodium salt derived from glutamic acid, is widely used in commercial food products to improve taste, quality, and preservation. However, its consumption may have detrimental effects on male reproductive function. Nevertheless, plant extracts, such as Lepidium meyenii (Maca), Trigonella foenum-graecum (Fenugreek), Spirulina platensis (Spirulina), and Tribulus arabica (Tribulus), may ameliorate these adverse effects. To this effect, the phytochemical properties of Lepidium meyenii, Trigonella foenum-graecum, Spirulina platensis, and Tribulus arabica were assessed, and their potential impact on MSG-induced impairment of reproductive parameters was examined. The phytochemical composition (steroids, terpenes, phenols, flavonoids) of the plants was profiled through spectrophotometry and the antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Thirty-six male Wistar rats were divided into six groups at random: a control group receiving distilled water, and five experimental groups (MSG, Maca, Fenugreek, Spirulina, and Tribulus) receiving 900 mg/kg/day of MSG dissolved in water for 45 days. Subsequently, the animals in the experimental groups were administered 500 mg/kg/day of the respective plant extract via oral gavage for an additional 35 days, while the MSG group continued to receive water only. Following the treatment period, the animals were sacrificed, and their reproductive tract organs were collected, weighed, and subjected to further analysis. Phytochemical analysis revealed the presence of diverse bioactive elements in the plant extracts, including phenolic and flavonoid compounds. Exposure to MSG negatively impacted total and progressive sperm motility, which was ameliorated by Lepidium meyenii treatment. Sperm morphology showed no significant differences among groups. Treatment of the phytochemical agents diminished histomorphometric alternations of the testicular length, germinal epithelium height, and number of cells in seminiferous tubules, which were caused by the initial administration of MSG. Testosterone and LH levels were reduced in the MSG group but improved in extract-treated groups. The study suggests Lepidium meyenii as a potential remedy for reproductive dysfunction. However, further investigation into its mechanisms and human safety and efficacy is warranted.

Abstract Purpose Prognostic factors have been well described for osteosarcoma, but analyses evaluating the further course of long‐term survivors are lacking. We used the large database of the Cooperative Osteosarcoma Study Group (COSS) to perform such an analysis. Patients and Methods The COSS database 1980‐04/2019 was searched for 5‐year survivors of primary high‐grade central osteosarcoma of the extremities or trunk. Identified patients were analyzed for their further survival outcomes, assessing potentially prognostic and predictive factors already evident at initial disease presentation and treatment as well as their disease course during the first 5 years of follow‐up. Results Two thousand and nine former eligible patients were identified (median age at initial diagnosis 15.1 (2.5–63.0) years; male vs. female 1149 (57.2%) vs. 860 (42.8%); extremities vs. trunk 1927 (95.9%) vs. 82 (4.1%); extremity primaries

Osteosarcoma is a challenging disease requiring multidisciplinary management in expert centers for optimal outcome. There are no current international protocols or guidelines specific for pediatric and adolescent osteosarcoma. The European Standard Clinical Practice (ESCP) project is a collaboration between ERN PaedCan and SIOP Europe’s Clinical Trial Groups to develop approved clinical recommendations reflecting current best practice. This manuscript is a summary of the full ESCP guideline for patients with osteosarcoma. The manuscript provides evidence graded recommendations for diagnosis, staging, management, response evaluation and follow-up. The methodology as defined in the standard operating procedures of the European Society for Medical Oncology (ESMO) was applied. Experts of the Fight OsteoSarcoma Through European Research (FOSTER) consortium contributed. In summary, the ESCP provides guidance on low-grade, but has a focus on high-grade osteosarcoma. In high-grade osteosarcoma the outcomes of most recent trials for clinical subgroups (e.g., metastatic vs. non-metastatic, resectable vs. non-resectable) are discussed, for treatment-naïve as well as for recurrent/refractory disease. An overview of current evidence also highlights the need for further therapeutic development as patients with primary metastatic or recurrent/refractory high-grade osteosarcoma still have a poor prognosis. Intensified collaborative research is identified as a prerequisite to increase survival and to limit long-term toxicities.

The figure of Viktor Ivanovich Nesmelov, a Kazan based theologian, is of a special importance among the variety of Russian theological movements. His anthropological views take stem from an intention to reconcile a traditional view for the Christian Orthodox theology — a biblical narrative of the creation of man, as well as the patristic anthropological teaching with psychological, philosophical data and the data of natural sciences contemporary with Nesmelov’s active years. That intention was gradually unfolding into an original theological and philosophical teaching, which was based on the category of person. However, in spite of the authenticity of the author’s anthropological ideas, some views of another philosophical movement show themselves in particular moments of V. I. Nesmelov’s teaching. By the time of V. I. Nesmelov’s active years that movement had already been grounded in Russian thought and had formed, albeit somewhat incoherent, a very traceable intellectual tradition. It was the ideas of Neo-Leibnizianism movement representatives. The latter had Leibniz’s Monadology as their ideological source, although, ideological diversity, in general, was their peculiarity. Another characteristic of that movement was the personalistic emphasis in their ideas, which in some cases was of a key role. Some researchers note that Neo-Leibnizianists in most cases tended to disassociate themselves from the abovementioned tradition. This to some extent unites the former with V. I. Nesmelov, taking both him and Neo-Leibnizianists from the frames of a fixed intellectual tradition into a field of diversity and originality of their teachings. In this article an effort is taken to express the personalistic teaching of V. I. Nesmelov as well as to compare his ideas with the views of some representatives of Neo-Leibnizianism. The ideological vagueness of the latter movement gives some space to undertake such comparison, which is localized, in this case, in the particular moments of V. I. Nesmelov’s teaching. An effort is taken as well to define the author’s ideas, taking into account his personal methodological emphasis.

Several theoretical studies have predicted that refrigerant mixtures with glides of more than 20 K can yield COP improvements in heat pumps for operating conditions where the temperature difference between the heat source and heat sink is large, but experimental validations and quantifications are scarce. The application of high-glide mixtures (>20 K) in industrial heat pumps in the field is, therefore, still hampered by concerns about the behavior and handling of the mixtures. This study experimentally investigates hydrocarbon (HC) mixtures R-290/600 (propane/butane) and R-290/601 (propane/pentane) and compares them to previously tested mixtures of synthetic refrigerants. Comprehensive evaluations are presented regarding COP, compressor performance, pressure drop, heat transfer, and the possibility of inline composition determination. The mixtures were tested over a range of compositions at a source inlet temperature of 60 °C and a sink outlet temperature of 100 °C, with the heat sink and heat source temperature differences controlled to 35 K. R-290/601 at a mass composition of 70%/30% was found as the best mixture with a COP improvement of 19% over R-600 as the best pure fluid. The overall isentropic compressor efficiency was similar for HC and synthetic refrigerants, given equal suction and discharge pressures. Pressure drops in heat exchangers and connecting lines were equal for synthetic and HC mixtures at equal mass flow rates. This allows higher heating capacities of HC mixtures at a given pressure drop (mass flow rate) due to their wider vapor dome. A previously developed evaporator heat transfer correlation for synthetic refrigerant mixtures was applicable to the HC mixtures. A condenser heat transfer correlation previously fitted for synthetic refrigerants performed significantly worse for HC mixtures. Composition determination during operation and without sampling was possible with a deviation of at most 0.05 mass fraction using simple temperature and pressure measurements and REFPROP for thermodynamic property calculations. Overall, high-glide HC mixtures, just like mixtures of synthetic refrigerants, showed significant COP improvements for specific operating conditions despite a decreased heat transfer coefficient. Potential problems like composition shift or poor compressor performance were not encountered. As a next step, testing high-glide mixtures in pilot-plant installations is recommended.

Reaction mixtures of naturally abundant aldoses and CH nucleophiles allow for the formation of functionalized furan precursors using low temperatures and metal-free catalysis in aqueous solutions of dilute base catalysts. We employ in situ NMR assays to clarify the mechanism and kinetics of the conversion. Catalysis serves a double role in ring-opening of stable aldoses such as glucose and xylose and facilitating the subsequent reactions with CH acids such as malononitrile or cyanoacetamide. Resultant acyclic products are shown to convert quickly to a monocyclic product prior to the slower formation of a more stable bicyclic intermediate and dehydration to tri-functionalized furan. Especially the reversible 5-exo-dig ring closure entailing oxygen attack onto a nitrile carbon is surprisingly fast with an equilibrium vastly towards the cyclic state, sequestering reactive groups and allowing the selective conversion to tri-functionalized furan. The reaction hinges on the fast formation of intermediates without CH acidity and competes with the oligomerization of CH nucleophiles. Insight derived from in situ NMR analysis shows the prowess of high-resolution in situ spectroscopy in clarifying the interplay between catalysts and reactants. Such insight will be vital for the optimization of reactions that upgrade biorenewables under benign conditions.

Chain elongation of unprotected carbohydrates in water under mild conditions remains a challenge both in chemical and biochemical synthesis. The Knoevenagel addition or condensation enables transformations to bioactive scaffolds for pharmaceutical and agrochemical compounds. Unfortunately, the catalysts in use for these transformations often reduce the green metrics of the transformations. Here, we use in situ NMR visualizations to explore the prospective use of natural catalysts for the synthesis of triple- and quadruple-functionalized furan- or dihydrofuran-derivatives from glucose and malononitrile. The dihydrofuran derivatives are formed as kinetic, major intermediates in the pathway to furan derivatives when using naturally abundant MgO or bio-sourced chitosan and N-Methyl-d-glucamine (meglumine) as the catalysts in water. Both catalyst loading, solvent composition and pH can be adapted to populate dihydrofurans with four substituents by slowing down their further reactions. Higher temperatures and higher pH values favor the formation of triple-functionalized furans over quadruple-substituted dihydrofurans, which may be bicyclic or monocyclic. Compared to more traditional catalysts, nature-sourced options offer more sustainable options that emulate natural processes. Visualization with in situ NMR contributes to streamlining the development of cheap and environmentally benign procedures for carbohydrate chain elongation.

The use of bicycles can provide myriad benefits to society, especially in crowded urban centres where other modes of transport are at or near capacity. However, integrating cycling into policy and planning requires more comprehensive data about their use in space and time. Current approaches, using sparse networks of counters provide one possible route to more comprehensive data. In this paper we investigate another, using data collected from Paris’ bicycle sharing system to explore use during 2020. We chose 2020 as a test year because the use of bicycles was strongly influenced by the COVID-19 pandemic, allowing us to explore how bicycle use adapted to both legal and environmental influences. We used interactive visualization to allow hypothesis generation and data exploration, before analysing bicycle use as a function of weather and COVID-19 restrictions. Our results show that bicycle sharing system data and Paris’ counters both capture very similar behaviour patterns, and therefore bicycle sharing system data are a reliable proxy for overall cycling behaviour, providing finer spatial granularity than existing sparse counter networks. Seasonally, precipitation influenced bicycle use more strongly in 2020 than COVID-19 measures.

Introduction: Rooibos (Aspalathin linearis), honeybush (Cyclopia intermedia), and sutherlandia (Sutherlandia frutescene) are three Southern Africa indigenous plants, of which the extracts have become house-hold items and are consumed on a large scale. Although, they are known for their antioxidant properties, studies have highlighted danger in the excessive intake. Therefore, the current study investigated whether treatment with rooibos, honeybush, and sutherlandia will impact sperm functional parameters positively or otherwise, in healthy rats.Methods: Fourteen-week-old pathogen-free adult male Wistar rats (250–300 g) were randomly divided into four groups of ten, including a control, rooibos (RF), honeybush (HB) and a sutherlandia (SL) group. After 7 weeks of treatment, animals were sacrificed. Spermatozoa were retrieved from the cauda epididymis for motility, morphology and concentration analysis and the testis was used for all biochemical assays.Results: The infusion treated animals (RF, HB, and SL) presented with a non-significant decrease of −14.3%, −18.2%, −17.2% and −24.8%, −20.7%, −27.3% in total motility and progressive motility when compared to the control group, respectively. There was a significant increase in number of spermatozoa with slow speed (p = 0.03), especially in SL treated group compared to the control (p = 0.03). Additionally, there was an increase of 28.8%, 31.7%, 23% in superoxide dismutase (SOD) activity of RF, HB and SL compared to control, respectively. This was accompanied with a percentage decrease of −21.1%, −23.7%, 45.9% in malondialdehyde (MDA) levels compared to the control group.Conclusion: In summary, animals treated with the respective infusions presented with a percentage increase in SOD activity but have reduced sperm motility and decreased normal morphology. Paradoxically, they presented with increased sperm concentration. Hence, it is presumed that rooibos, honeybush and sutherlandia may enhance sperm quantity (concentration) but may impair sperm quality (motility morphology) when consumed by healthy animals.

Air pollution, either from indoor (household) or outdoor (ambient) sources, occurs when there is presence of respirable particles in the form of chemical, physical, or biological agents that modify the natural features of the atmosphere or environment. Today, almost 2.4 billion people are exposed to hazardous levels of indoor pollution, while 99% of the global population breathes air pollutants that exceed the World Health Organization guideline limits. It is not surprising that air pollution is the world’s leading environmental cause of diseases and contributes greatly to the global burden of diseases. Upon entry, air pollutants can cause an increase in reactive oxygen species (ROS) production by undergoing oxidation to generate quinones, which further act as oxidizing agents to yield more ROS. Excessive production of ROS can cause oxidative stress, induce lipid peroxidation, enhance the binding of polycyclic aromatic hydrocarbons (PAHs) to their receptors, or bind to PAH to cause DNA strand breaks. The continuous and prolonged exposure to air pollutants is associated with the development or exacerbation of pathologies such as acute or chronic respiratory and cardiovascular diseases, neurodegenerative and skin diseases, and even reduced fertility potential. Males and females contribute to infertility equally, and exposure to air pollutants can negatively affect reproduction. In this review, emphasis will be placed on the implications of exposure to air pollutants on male fertility potential, bringing to light its effects on semen parameters (basic and advanced) and male sexual health. This study will also touch on the clinical implications of air pollution on male reproduction while highlighting the role of oxidative stress.

Abstract Azoospermia, which is the absence of spermatozoa in an ejaculate occurring due to defects in sperm production, or the obstruction of the reproductive tract, affects about 1% of all men and is prevalent in up to 10–15% of infertile males. Conventional semen analysis remains the gold standard for diagnosing and treating male infertility; however, advances in molecular biology and bioinformatics now highlight the insufficiency thereof. Hence, the need to widen the scope of investigating the aetiology of male infertility stands pertinent. The current study aimed to identify common differentially expressed genes (DEGs) that might serve as potential biomarkers for non-obstructive azoospermia (NOA) and overall male infertility. DEGs across different datasets of transcriptomic profiling of testis from human patients with different causes of infertility/ impaired spermatogenesis and/or azoospermia were explored using the gene expression omnibus (GEO) database. Following the search using the GEOquery, 30 datasets were available, with 5 meeting the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEO2R tool. The annotated genes of the probes in each dataset were intersected with DEGs from all other datasets. Enriched Ontology Clustering for the identified genes was performed using Metascape to explore the possible connection or interaction between the genes. Twenty-five DEGs were shared between most of the datasets, which might indicate their role in the pathogenesis of male infertility. Of the 25 DEGs, eight genes (THEG, SPATA20, ROPN1L, GSTF1, TSSK1B, CABS1, ADAD1, RIMBP3) are either involved in the overall spermatogenic processes or at specific phases of spermatogenesis. We hypothesize that alteration in the expression of these genes leads to impaired spermatogenesis and, ultimately, male infertility. Thus, these genes can be used as potential biomarkers for the early detection of NOA.

Abstract This article examines the spatially varying effect of age on single-family house (SFH) prices. Age has been shown to be a key driver for house depreciation and is usually associated with a negative price effect. In practice, however, there exist deviations from this behavior which are referred to as vintage effects. We estimate a spatially varying coefficients (SVC) model to investigate the spatial structures of vintage effects on SFH pricing. For SFHs in the Canton of Zurich, Switzerland, we find substantial spatial variation in the age effect. In particular, we find a local, strong vintage effect primarily in urban areas compared to pure depreciative age effects in rural locations. Using cross validation, we assess the potential improvement in predictive performance by incorporating spatially varying vintage effects in hedonic models. We find a substantial improvement in out-of-sample predictive performance of SVC models over classical spatial hedonic models.

Abstract Background Affordable conventional semen analysis remains a fundamental procedure to be performed routinely during the diagnosis of male infertility. Advanced semen analyses provide valuable clinical insights in treatment-related decision-making, but these are highly expensive and lack universal standardization. This study aimed at determining the relationship between conventional semen parameters, measured with assistance of computer-aided sperm analysis (CASA), and a set of advanced semen tests. Basic semen analysis (n = 124) was performed according to the World Health Organization (WHO) guidelines. Sperm DNA fragmentation and intracellular superoxide (O2 −•) levels were assessed by flow cytometry. Seminal plasma thiobarbituric acid reactive substances (TBARS) levels as well as superoxide dismutase (SOD) and catalase (CAT) activity were measured by spectrophotometry. Spearman’s rank correlation coefficient was used, with significance set at p < 0.05. Results Semen pH correlated negatively with TBARS (p < 0.01). The proportions of total and progressively motile as well as rapid spermatozoa correlated positively with CAT activity (p < 0.05). Sperm viability correlated negatively with both O2 −• (p < 0.05) and DNA fragmentation (p = 0.01), while normal morphology correlated negatively with O2 −• levels (p < 0.05) and positively with CAT activity (p < 0.05). Straight-line velocity (VCL) and average-path velocity (VAP) correlated negatively with both O2 −• (p < 0.01) and TBARS (p < 0.01). Amplitude of lateral head displacement (ALH) correlated negatively with O2 −• (p < 0.01) and DNA fragmentation (p < 0.01), while its correlation with SOD activity was positive (p < 0.05). Conclusion The results obtained from this study support the validity of some CASA parameters as sensitive indicators of changes in sperm oxidative status and DNA integrity. Predicting advanced from conventional parameters through the building of linear regression models should be considered for future studies.

IntroductionCraniofacial bones may be the site of origin of various sarcomas. We review the various malignancies affecting this region of the body and attempt to put systemic treatment approaches into perspective.Material and methodsNon-systematic literature reviewResultsConventional types of osteosarcoma, Ewing sarcoma, and chondrosarcoma are the most frequent bone sarcomas occurring in craniofacial region, but variants may occur. The tumors’ biologies and the resulting treatment strategies vary distinctly. As a general rule, local control remains paramount regardless of histology. The efficacy of antineoplastic chemotherapy varies by type of malignancy. It is clearly indicated in Ewing sarcoma and related tumors, potentially of benefit in high-grade osteosarcoma, undifferentiated pleomorphic sarcoma, dedifferentiated and mesenchymal chondrosarcoma, and of no proven benefit in the others.ConclusionsVarious histologies demand various and distinct treatment approaches, with local control remaining paramount in all. The efficacy of systemic treatments varies by type of tumor. Prospective trials would help in all of these to better define systemic treatment strategies.

Many enzymes have latent activities that can be used in the conversion of non-natural reactants for novel organic conversions. A classic example is the conversion of benzaldehyde to a phenylacetyl carbinol, a precursor for ephedrine manufacture. It is often tacitly assumed that purified enzymes are more promising catalysts than whole cells, despite the lower cost and easier maintenance of the latter. Competing substrates inside the cell have been known to elicit currently hard-to-predict selectivities that are not easily measured inside the living cell. We employ NMR spectroscopic assays to rationally combine isomers for selective reactions in commercial S. cerevisiae. This approach uses internal competition between alternative pathways of aldehyde clearance in yeast, leading to altered selectivities compared to catalysis with the purified enzyme. In this manner, 4-fluorobenzyl alcohol and 2-fluorophenylacetyl carbinol can be formed with selectivities in the order of 90%. Modification of the cellular redox state can be used to tune product composition further. Hyperpolarized NMR shows that the cellular reaction and pathway usage are affected by the xenochemical. Overall, we find that the rational construction of ternary or more complex substrate mixtures can be used for in-cell NMR spectroscopy to optimize the upgrading of similar xenochemicals to dissimilar products with cheap whole-cell catalysts.

With the advancement in space exploration and the intention to establish an inhabitable human settlement on Mars, it is important to investigate the effects of exposure to space/microgravity and the associated radiations on procreation. Sperm function and integrity are fundamental to male reproduction and can potentially be affected by the environmental changes experienced in space. Therefore, this study was conducted to systematically gather, filter, and collate all the relevant information on the effects of spaceflight on male reproductive parameters and functions. A search was performed utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were extracted from the major electronic databases including PubMed, and other credible literature sources. MeSH search terms that were employed included “spermatozoa”, “microgravity”, and “ionizing radiation”. The literature search did not discriminate against papers published before a certain date due to the very limited number of articles available. However, there was a restriction on the male gender and language (English). The parameters included in this study are sperm motility, total sperm count, sperm DNA fragmentation hormonal levels and testicular histology. Following a comprehensive literature search, a total of 273 articles were retrieved and screened, 252 articles were excluded due to the irrelevance to the topic, duplication, and non-original articles. A total of 21 articles met the inclusion criteria and are included in the current study. Findings from these studies showed that sperm motility was decreased after exposure to microgravity and ionizing radiation. Total sperm count was also found to be reduced by microgravity only. Sperm DNA fragmentation was increased by both ionizing radiation and microgravity. Testosterone levels and testicular weight were also decreased by microgravity. Although there is a dearth in the literature regarding the effects of microgravity and ionizing radiation on male reproductive parameters, the available findings showed that exposure to microgravity poses a risk to male reproductive health. Therefore, it is essential to develop countermeasures to either manage, treat, or prevent these consequential adverse effects. Hence, this review also highlights some potential countermeasure approaches that may mitigate the harmful effects of microgravity and associated exposures on male reproductive health.

Male infertility is attributable to 60% of total infertility cases and about 30-50% of these cases remain idiopathic. In the Middle East and North Africa region (MENA), male infertility affects about 22.6% of men of reproductive age. Male infertility is caused by a variety of factors, including endocrine disruption, exposure to toxins, lifestyle, genetic and epigenetic modifications. Genetic modifications, including chromosomal abnormalities, chromosomal rearrangements, Y chromosome microdeletions and single-gene mutations, explain for about 10-15% of infertility cases. Since genetic aberration is a key player in the pathogenesis of male infertility, it is important to explore the impact in the MENA region due to the high incidence of male infertility. Therefore, the current study aims to systematically analyse the literature regarding the impact and common causes of male infertility in the MENA region. To achieve this aim, a comprehensive literature search was performed on PubMed, Google Scholar, and Science Direct databases. Following the search, a total of 126 articles was retrieved, of which 12 were duplicates and another 69 articles did not meet the inclusion criteria, totaling the exclusion of 81 articles. Studies excluded were those that had patient populations originating outside the MENA region, review articles, non-English written articles, or studies where the patient population was under 18 years of age. Findings showed that the frequent genetic aberration leading to male infertility in these regions include Y chromosome microdeletions, gene polymorphisms or copy number variations, mitochondrial microdeletions and other genetic deletions or mutations. In lieu of this, diverse clinical genetic tests should be made available for the proper diagnosis of male infertility.

Statins have been shown to cause diverse male reproductive function impairment, and in some cases, orchialgia. Therefore, the current study investigated the possible mechanisms through which statins may alter male reproductive parameters. Thirty adult male Wistar rats (200–250 g) were divided into three groups. The animals were orally administered rosuvastatin (50 mg/kg), simvastatin (50 mg/kg), or 0.5% carboxy methyl cellulose (control), for a 30-day period. Spermatozoa were retrieved from the caudal epididymis for sperm analysis. The testis was used for all biochemical assays and immunofluorescent localization of biomarkers of interest. Rosuvastatin-treated animals presented with a significant decrease in sperm concentration when compared to both the control and simvastatin groups (p < 0.005). While no significant difference was observed between the simvastatin and the control group. The Sertoli cells, Leydig cells and whole testicular tissue homogenate expressed transcripts of solute carrier organic anion transporters (SLCO1B1 and SLCO1B3). There was a significant decrease in the testicular protein expression of the luteinizing hormone receptor, follicle stimulating hormone receptor, and transient receptor potential vanilloid 1 in the rosuvastatin and simvastatin-treated animals compared to the control. The expression of SLCO1B1, SLCO1B2, and SLCO1B3 in the different spermatogenic cells portray that un-bio transformed statin can be transported into the testicular microenvironment, which can subsequently alter the regulation of the gonadal hormone receptors, dysregulate pain-inflammatory biomarkers, and consequently impair sperm concentration.

Objective: To investigate the testicular oxidative stress and apoptosis status, as well as the sperm functional parameters in streptozotocin (STZ) induced diabetic rats following treatment with rooibos (Aspalathus linearis), honeybush (Cyclopia intermedia) and sutherlandia (Lessertia frutescens) infusions. Methods: Diabetes was induced by injecting fourteen-week-old adult male Wistar rats (250-300 g) with a single intraperitoneal injection of STZ (45 mg/kg body weight). Fifty rats were randomly divided into five groups: the vehicle group received 0.1 M citrate buffer, the diabetic control group received 45 mg/kg STZ, the diabetic+rooibos group received 45 mg/kg STZ + 2.0% rooibos, the diabetic+honeybush group received 45 mg/kg STZ + 4.0% honeybush, and the diabetic+sutherlandia group received 45 mg/kg STZ + 0.2% sutherlandia. Rats were sacrificed 7 weeks after induction of diabetes mellitus. The testes and epididymides were harvested and weighed after induction. Spermatozoa were retrieved from the cauda epididymis for motility, concentration, and morphology analysis, and the testis was used for all biochemical assays. Oxidative stress was determined by measuring malondialdehyde levels, catalase, and superoxide dismutase activities, while apoptotic biomarkers were evaluated by Western blotting assays. Results: After induction of diabetes, rats in the diabetic control group, diabetic+rooibos group, diabetic+honeybush group, and diabetic+sutherlandia group presented with significantly elevated blood glucose levels as compared with the vehicle group (P

Objective: To evaluate the testis and the cauda epididymis after treating both healthy and diabetic rats with rooibos (Aspalathus linearis), honeybush (Cyclopia intermedia), and sutherlandia (Lessertia frutescens), respectively. Methods: Ninety male Wistar rats were randomly divided into nine groups (n=10 per group). Fifty rats were randomized to receive tap water, 0.1 M citrate buffer, 2.0% fermented rooibos, 4.0% fermented honeybush, or 0.2% unfermented sutherlandia. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ) at 45 mg/kg in 40 rats. The diabetic rats were randomized to receive tap water, 2.0% fermented rooibos, 4.0% fermented honeybush, or 0.2% unfermented sutherlandia. Rats were sacrificed after seven weeks of diabetic induction. Blood was collected for hormonal assay, while the testes and caudal epididymis were retrieved for histomorphological evaluations. Results: Diabetic rats treated with 2.0% fermented rooibos exhibited a significant increase in fasting plasma glucose (FPG) versus the vehicle group (P=0.002), and a 3.6% decrease compared to the diabetic control group (P>0.05). Diabetic rats treated with honeybush or sutherlandia showed 23.6% and 15.4% decrease in FPG when compared to the diabetic control group, respectively (both P>0.05). The diabetic control rats had a significant decrease in the percentage of histologically normal seminiferous tubules compared to the control group (P=0.049). There was 21.0%, 14.0%, and 5.4% rise in the percentage of normal seminiferous tubules in diabetic rats receiving rooibos, honeybush or sutherlandia, respectively, compared to the diabetic control group. The infusion control groups (rooibos, honeybush and sutherlandia) showed normal seminiferous tubules, presence of spermatozoa in the epididymal lumen, and had normal overall architecture. Both testicular and epididymal morphology were altered in the diabetic control group, but these disruptions were mildly ameliorated by rooibos, honeybush, and sutherlandia. Conclusions: The detrimental effects of diabetes on the histomorphological architecture of the testis and epididymis are mildly ameliorated by the infusions (2.0% fermented rooibos, 4.0% fermented honeybush, and 0.2% unfermented sutherlandia).

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male infertility has lately received significant attention. SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) in humans, has been shown to impose adverse effects on both the structural components and function of the testis, which potentially impact spermatogenesis. These adverse effects are partially explained by fever, systemic inflammation, oxidative stress, and an increased immune response leading to impaired blood-testis barrier. It has been well established that efficient cellular communication via gap junctions or functional channels is required for tissue homeostasis. Connexins and pannexins are two protein families that mediate autocrine and paracrine signaling between the cells and the extracellular environment. These channel-forming proteins have been shown to play a role in coordinating cellular communication in the testis and epididymis. Despite their role in maintaining a proper male reproductive milieu, their function is disrupted under pathological conditions. The involvement of these channels has been well documented in several physiological and pathological conditions and their designated function in infectious diseases. However, their role in COVID-19 and their meaningful contribution to male infertility remains to be elucidated. Therefore, this review highlights the multivariate pathophysiological mechanisms of SARS-CoV-2 involvement in male reproduction. It also aims to shed light on the role of connexin and pannexin channels in disease progression, emphasizing their unexplored role and regulation of SARS-CoV-2 pathophysiology. Finally, we hypothesize the possible involvement of connexins and pannexins in SARS-CoV-2 inducing male infertility to assist future research ideas targeting therapeutic approaches.

Rad se bavi ispitivanjem intertekstualnih i poetičkih veza Tekerijevog (Thackeray) romana Vašar taštine (Vanity Fair) i romana Lomača taština (Bonfire of the Vanities) Toma Vulfa (Tom Wolfe). Polazeći od problema intertekstualnih teorija, analiza se odvija prema sistematizaciji Žerara Ženeta (Genette). Rasvetljavaju se mogući odnosi između dva romana koji se ispituju na samim tekstovima, a potom pronalaze i u Vulfovoj eksplicitnoj poetici. Prate se intertekstualne veze naslova, serijalizovane forme oba romana i razmatra njihov uticaj na strukturu dela. Potom se razmatraju različiti aspekti mikrostruktura oba romana (elementi zapleta, pripovedne tehnike) i eksplicira smisao Vulfovih adaptacija Tekerijevog modela. Konačno, opažene odlike stavljaju se u kontekst Vulfove eksplicitne poetike i stanovišta obnove realističkog romana, gde se roman Lomača taština ostvaruje kao jedan od utemeljujućih tekstova neorealizma.

Male fertility potential can be influenced by a variety of conditions that frequently coincide. Spermatozoa are particularly susceptible to oxidative damage due to their limited antioxidant capacity and cell membrane rich in polyunsaturated fatty acids (PUFAs). The role of oxidative stress (OS) in the etiology of male infertility has been the primary focus of our Stellenbosch University Reproductive Research Group (SURRG) over the last 10 years. This review aims to provide a novel insight into the impact of OS on spermatozoa and male reproductive function by reviewing the OS-related findings from a wide variety of studies conducted in our laboratory, along with those emerging from other investigators. We will provide a concise overview of the production of reactive oxygen species (ROS) and the development of OS in the male reproductive tract along with the physiological and pathological effects thereof on male reproductive functions. Recent advances in methods and techniques used for the assessment of OS will also be highlighted. We will furthermore consider the current evidence regarding the association between OS and ejaculatory abstinence period, as well as the potential mechanisms involved in the pathophysiology of various systemic diseases such as obesity, insulin resistance, hypertension, and certain mental health disorders which have been shown to cause OS induced male infertility. Finally, special emphasis will be placed on the potential for transferring and incorporating research findings emanating from different experimental studies into clinical practice.

The well-known 3-hydroxyl 3-methyl glutaryl-Coenzyme A reductase inhibitors, called statins, have been the main medication used in the treatment of hypercholesterolemia and some cases of cardiovascular diseases. The effectiveness of this drug in controlling cholesterol production is impeccable, however, patients often complain of a variety of side effects, such as myalgia, muscle atrophy, and in some cases, rhabdomyolysis. Not only has the use of statins caused the aforementioned side effects, but they are also shown to cause testicular discomfort, erectile dysfunction, altered semen parameters, and modified steroid hormone production. These reported adverse effects on male fertility are not generally agreed upon, as some have shown the use to be beneficial. Hence, this makes the aftermath effect of statin use on male fertility debatable and controversial. The negative effects have been associated with imbalanced or reduced steroid hormones, which are necessary for proper spermatogenesis and other sexual functions. Meanwhile, the beneficial effects are related to statin’s anti-inflammatory and cardioprotective properties. These contradictory findings are in part due to the different age of users, concentrations of statins, the type and duration of treatment, and the underlying disease and/or comorbidities. Therefore, the current study aims to analyze the literature and gather evidence as to the effects of statin on male sexual health and reproductive parameters, and subsequently give recommendations for the direction of future studies.

The COVID-19 pandemic has forced universities worldwide to immediately transition to distance-learning. Although numerous studies have investigated the effect of the COVID-19 pandemic on universities in the Middle East, none have reflected on the process through which medical education programs for health professions underwent this transition. This study aimed to elucidate the rapid transition to distance-learning of an undergraduate medical program at the College of Medicine, Mohammad Bin Rashid University of Medicine and Health Sciences (Dubai, United Arab Emirates), owing to the COVID-19 pandemic. An action research approach constituted the foundation of this collaborative effort that involved investigations, reflections, and improvements of practice, through ongoing cycles of planning, acting, observing, and reflecting. Efforts of transitioning to distance-learning were grouped into four interrelated aspects: supporting faculty members in delivering the program content, managing curriculum changes, engaging with the students to facilitate distance-learning experiences, and conducting web-based assessments. Challenges included the high perceived uncertainty, need for making ad hoc decisions, lack of experiential learning and testing of clinical skills, and blurring of work-life boundaries. Our preliminary findings show the successful generation of a strong existing digital base, future prospects for innovation, and a cohesive team that was key to agility, rapid decision-making, and program implementation.

Abstract Background To evaluate optimal therapy and potential risk factors. Methods Data of DSRCT patients

Short linear motifs (SLiMs) are short linear sequences that can mediate protein–protein interaction. Mimicking eukaryotic SLiMs to compete with extra- or intracellular binding partners, or to sequester host proteins is the crucial strategy of viruses to pervert the host system. Evolved proteins in viruses facilitate minimal protein–protein interactions that significantly affect intracellular signaling networks. Unfortunately, very little information about SARS-CoV-2 SLiMs is known, especially across SARS-CoV-2 variants. Through the ELM database-based sequence analysis of spike proteins from all the major SARS-CoV-2 variants, we identified four overriding SLiMs in the SARS-CoV-2 Omicron variant, namely, LIG_TRFH_1, LIG_REV1ctd_RIR_1, LIG_CaM_NSCaTE_8, and MOD_LATS_1. These SLiMs are highly likely to interfere with various immune functions, interact with host intracellular proteins, regulate cellular pathways, and lubricate viral infection and transmission. These cellular interactions possibly serve as potential therapeutic targets for these variants, and this approach can be further exploited to combat emerging SARS-CoV-2 variants.

IntroductionEvidence indicates children who suffer from ill-health are less likely to attend or complete schooling. Malaria is an important cause of morbidity and mortality in school-age children. However, they are less likely to receive malaria treatment at health facilities and evidence for how to improve schoolchildren’s access to care is limited. This study aimed to evaluate the impact of a programme of school-based malaria case management on schoolchildren’s attendance, health and education.MethodsA cluster randomised controlled trial was conducted in 58 primary schools in Zomba District, Malawi, 2011–2015. The intervention, implemented in 29 randomly selected schools, provided malaria rapid diagnostic tests and artemisinin-based combination therapy to diagnose and treat uncomplicated malaria as part of basic first aid kits known as ‘Learner Treatment Kits’ (LTK). The primary outcome was school attendance, assessed through teacher-recorded daily attendance registers and independent periodic attendance spot checks. Secondary outcomes included prevalence of Plasmodium spp infection, anaemia, educational performance, self-reported child well-being and health-seeking behaviour. A total of 9571 children from standards 1–7 were randomly selected for assessment of school attendance, with subsamples assessed for the secondary outcomes.ResultsBetween November 2013 and March 2015, 97 trained teachers in 29 schools provided 32 685 unique consultations. Female schoolchildren were significantly more likely than male to seek a consultation (unadjusted OR=1.78 (95% CI 1.58 to 2.00). No significant intervention effect was observed on the proportion of child-days recorded as absent in teacher registers (n=9017 OR=0.90 (95% CI 0.77 to 1.05), p=0.173) or of children absent during random school visits—spot checks (n=5791 OR=1.09 (95% CI 0.87 to 1.36), p=0.474). There was no significant impact on child-reported well-being, prevalence of Plasmodium spp, anaemia or education scores.ConclusionDespite high community demand, the LTK programme did not reduce schoolchildren’s absenteeism or improve health or education outcomes in this study setting.Trial registration numberClinicalTrials.gov NCT02213211.

Male infertility is a multifaceted disorder affecting approximately 50% of male partners in infertile couples. Over the years, male infertility has been diagnosed mainly through semen analysis, hormone evaluations, medical records and physical examinations, which of course are fundamental, but yet inefficient, because 30% of male infertility cases remain idiopathic. This dilemmatic status of the unknown needs to be addressed with more sophisticated and result-driven technologies and/or techniques. Genetic alterations have been linked with male infertility, thereby unveiling the practicality of investigating this disorder from the “omics” perspective. Omics aims at analyzing the structure and functions of a whole constituent of a given biological function at different levels, including the molecular gene level (genomics), transcript level (transcriptomics), protein level (proteomics) and metabolites level (metabolomics). In the current study, an overview of the four branches of omics and their roles in male infertility are briefly discussed; the potential usefulness of assessing transcriptomic data to understand this pathology is also elucidated. After assessing the publicly obtainable transcriptomic data for datasets on male infertility, a total of 1385 datasets were retrieved, of which 10 datasets met the inclusion criteria and were used for further analysis. These datasets were classified into groups according to the disease or cause of male infertility. The groups include non-obstructive azoospermia (NOA), obstructive azoospermia (OA), non-obstructive and obstructive azoospermia (NOA and OA), spermatogenic dysfunction, sperm dysfunction, and Y chromosome microdeletion. Findings revealed that 8 genes (LDHC, PDHA2, TNP1, TNP2, ODF1, ODF2, SPINK2, PCDHB3) were commonly differentially expressed between all disease groups. Likewise, 56 genes were common between NOA versus NOA and OA (ADAD1, BANF2, BCL2L14, C12orf50, C20orf173, C22orf23, C6orf99, C9orf131, C9orf24, CABS1, CAPZA3, CCDC187, CCDC54, CDKN3, CEP170, CFAP206, CRISP2, CT83, CXorf65, FAM209A, FAM71F1, FAM81B, GALNTL5, GTSF1, H1FNT, HEMGN, HMGB4, KIF2B, LDHC, LOC441601, LYZL2, ODF1, ODF2, PCDHB3, PDHA2, PGK2, PIH1D2, PLCZ1, PROCA1, RIMBP3, ROPN1L, SHCBP1L, SMCP, SPATA16, SPATA19, SPINK2, TEX33, TKTL2, TMCO2, TMCO5A, TNP1, TNP2, TSPAN16, TSSK1B, TTLL2, UBQLN3). These genes, particularly the above-mentioned 8 genes, are involved in diverse biological processes such as germ cell development, spermatid development, spermatid differentiation, regulation of proteolysis, spermatogenesis and metabolic processes. Owing to the stage-specific expression of these genes, any mal-expression can ultimately lead to male infertility. Therefore, currently available data on all branches of omics relating to male fertility can be used to identify biomarkers for diagnosing male infertility, which can potentially help in unravelling some idiopathic cases.

The 100,000th scientific article on the subject of spermatozoa was recently published. Numerous studies evaluated the characteristics of this important cell that led to tremendous discoveries. Since its first observation and description in 1677, many important characteristics have been described regarding this highly fascinating gamete. In this review, we intend to provide a historical account of the numerous milestones and breakthroughs achieved related to sperma- tozoa. We conducted a review of the literature by selecting the most important subjects with regards to spermatozoa. Since their discovery by van Leeuwenhoek, spermatozoa have been studied by scientists to better understand their physiology and process of interaction with their female counterpart, the oocyte, in order to treat and resolve infertility problems. Three centuries after van Leeuwenhoek’s discovery, the 100,000th article about these cells was published. It is encouraging that sperm research reached this landmark, but at the same time it is clear that further research on male reproductive physiology and spermatozoa is required to shed more light on their function and pathology in order to reduce the number of unexplained infertility cases.

Objective: To determine the effect of short (4 h) and long (4 days) abstinence periods on sperm quality based on functional and biochemical parameters in a population of normozoospermic men. Methods: Two semen samples were collected in succession from potentially fertile, normozoospermic men (n = 100) after an abstinence period of 4 days and 4 h respectively. The mean values of semen volume, pH, viscosity, sperm concentration, percentage of total and progressively motile sperm, sperm kinematics/velocity, normal morphology, acrosome status, DNA fragmentation, intracellular superoxide (O2−•) levels and seminal antioxidant status were compared between the two abstinence duration groups. Results: A significant increase in total and progressive motility and velocity parameter values were observed after short abstinence compared with long abstinence periods. Sperm DNA fragmentation and intracellular O2−• levels were not significantly different between the two abstinence periods. Despite the decrease in semen volume, sperm concentration and total sperm number after short abstinence periods, all mean values of the conventional semen parameters remained above the lower reference limits as reported by the WHO. Conclusion: The data from this most comprehensive study of its kind challenges the generally accepted guidelines of the prolonged abstinence periods since the results show that 4 h of sexual abstinence yielded significantly better sperm samples from a functional point of view. Although this study was performed on normozoospermic men, future studies with infertile men might yield similar findings that could lead to employing short abstinence as a strategy to improve the outcome of ART and fertility preservation.

Variation in the ejaculatory abstinence period suggested by different guidance bodies have resulted in a growing concern among researchers and clinicians over what the precise period of ejaculatory abstinence ought to be for an optimal semen sample. Several studies have thus been undertaken to examine the association between the length of sexual abstinence and semen characteristics. Not all studies, however, have arrived at the same conclusions. This study aims to review all existing literature published during the past few decades pertaining to the influence of ejaculatory abstinence on semen quality. For the purpose of this systematic review, all data related to sexual abstinence duration and seminal parameters were re-analysed to homogenize the current data. Thorough PubMed, MEDLINE and Google Scholar, a literature search was conducted using the keywords “sexual abstinence”, “ejaculatory abstinence”, “semen”, “spermatozoa”, “semen analysis”, “sperm parameters”, “motility”, “reactive oxygen species (ROS)” and “DNA fragmentation”. After carefully reviewing all the literature, 30 relevant papers, both written in English and published between January 1979 and December 2016, were included in this review. The weight of the evidence suggests that the decline in semen volume and sperm concentration with shorter abstinence periods is accompanied by a substantial improvement in sperm motility characteristics, especially progressive motility and velocity. Nevertheless, available data are insufficient to support definitive conclusions regarding the influence of the ejaculatory abstinence period on advanced semen parameters (ROS, DNA fragmentation and seminal plasma antioxidant capacity) and pregnancy rates. In conclusion, taking all data into account, shortening of the abstinence period may be beneficial to sperm quality. Furthermore, we recommend that the current guidelines regarding the prescribed abstinence period should be revisited.

Emerging evidence from in vivo as well as in vitro studies indicates that natural biomolecules may play important roles in the prevention or management of a wide array of chronic diseases. Furthermore, the use of natural compounds in the treatment of male sub- or infertility has been proposed as a potential alternative to conventional therapeutic options. As such, we aimed to evaluate the effects of selected natural biomolecules on the sperm production, structural integrity, and functional activity. At the same time, we reviewed their possible beneficial or adverse effects on male reproductive health. Using relevant keywords, a literature search was performed to collect currently available information regarding molecular mechanisms by which selected natural biomolecules exhibit their biological effects in the context of male reproductive dysfunction. Evidence gathered from clinical trials, in vitro experiments and in vivo studies suggest that the selected natural compounds affect key targets related to sperm mitochondrial metabolism and motion behavior, oxidative stress, inflammation, DNA integrity and cell death. The majority of reports emphasize on ameliorative, stimulating and protective effects of natural biomolecules on the sperm function. Nevertheless, possible adverse and toxic behavior of natural compounds has been indicated as well, pointing out to a possible dose-dependent impact of natural biomolecules on the sperm survival and functionality. As such, further research leading to a deeper understanding of the beneficial or adverse roles of natural compounds is necessary before these can be employed for the management of male reproductive dysfunction.

Background: Diabetes mellitus (DM) is widely reported to have adverse effect on most systems of the body. This study investigated the effects of DM on male reproductive parameters and possible role of aqueous leave extract from Basella alba in ameliorating such effects. Methods: Male rats (n = 40) aged 8-10 weeks were randomly divided into 4 equal groups: Healthy Control (HC), Diabetic Control (DC), Healthy Treatment (HT) and Diabetic Treatment (DT). Diabetes was induced in animal by using (STZ single intraperitoneal injection of streptozotocin (STZ), (55 mg/kg). Treatment was oral via gavage HC and DC groups received 0.5 ml/100 g normal saline daily via oral gavage, HT and DT groups received 200 mg/kg plant extract daily for 4 weeks. Fasting blood sugar and body weights were recorded weekly. Animals were sacrificed upon completion of treatments and tissues were collected for further analysis. Results: There was significant decrease in weights of the body, testis, and epididymis in DC compared to HC rats (P < 0.05). Relative testicular weight was significantly increased in both DC and DT compared to HC groups (P < 0.0001). Sperm concentration, viability and morphology, were all significantly reduced in DC versus HC rats (p

Background The quality of semen depends upon several factors such as environment, life style, physical activity, age, and occupation. The aim of this study was to analyze and compare the conventional and functional semen parameters in men practicing vigorous physical activity to those of sedentary men. Materials and Methods In this descriptive cross-sectional study, semen samples of 17 physically active men and 15 sedentary men were collected for analysis. Semen analysis was performed according to the World Health Organization (WHO) guidelines, while functional parameters were evaluated by flow cytometry. Results Results showed that several semen parameters (semen volume, viability, progressive motility, total motility, normal morphology, and moribund cells) were superior in the physically active group in comparison with the sedentary group. Semen parameters such as viability, progressive motility and total motility, as well as the percentage of moribund spermatozoa were significantly different between both groups. However, sperm DNA damage, lipid peroxidation and mitochondrial potential were not significantly different among the groups. Conclusion Nevertheless, the physical activity shows better semen parameters than sedentary group. Taken together, our results demonstrate that regular physical activity has beneficial impact in sperm fertility parameters and such a life style can enhance the fertility status of men.

Patients who are bedridden often suffer from muscular atrophy due to reduced daily activities and can become depressed. However, patients who undergo physical therapy sometimes demonstrate positive benefits including a reduction of stressful and depressed behavior. Regenerative medicine has seen improvements in two stem cell-based therapies for central nervous system disorders. One therapy is through the transfer of exogenous stem cells. The other therapy is a more natural method and focuses on the increasing endogenous neurogenesis and restoring the neurological impairments. This study overviews how immobilization-induced disuse atrophy affects neurogenesis in rats, specifically hypothesizing that immobilization diminishes circulating trophic factor levels, like vascular endothelial growth factors or brain-derived neurotrophic factor, which in turn limits neurogenesis. This hypothesis requires the classification of the stem cell microenvironment by probing growth factors in addition to other stress-related proteins that correlate with exercise-induced neurogenesis. There is research examining the effects of increased exercise on neurogenesis while limiting exercise, which better demonstrates the pathological states of immobile stroke patients, remains relatively unexplored. To examine the effects of immobilization on neurogenesis quantitative measurements of movements, 5-bromo-2deoxyuridine labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid and neurological levels of trophic factors, growth factors, and stress-related proteins will indicate levels of neurogenesis. In further research, studies are needed to show how in vivo stimulation, or lack thereof, affects stem cell microenvironments to advance treatment procedures for strengthening neurogenesis in bedridden patients. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

Trial registrationClinicalTrials.gov NCT02397772.

Objectives: Cotinine, the principal metabolite of nicotine found in smokers' seminal plasma, has been shown to adversely affect sperm functionality while quercetin, a flavonoid with diverse properties is associated with several in vivo and in vitro health benefits. The aim of this study was to investigate the potential benefits of quercetin supplementation against damage caused by the by-products of tobacco smoke in human sperm cells. Methods: Washed human spermatozoa from 10 normozoospermic donors were treated with nutrient medium (control), quercetin (30 μmol/L) and cotinine (190 μg/mL, 300 ng/mL) with or without quercetin for 60 and 180 min incubation periods. Computer-aided sperm analysis was used to assess sperm motility while acrosome-reacted cells were identified under a fluorescent microscope using fluorescein isothiocyanate-labelled Pisum Sativum Agglutinin as a probe, viability was assessed by means of a dye exclusion staining technique (eosin/nigrosin) and oxidative stress by flow cytometry using dihydroethidium as a probe. Values were expressed as mean ± S.E.M. as compared by ANOVA. Results: Higher cotinine concentrations reduced the number of viable cells after 60 and 180 min of exposure while viability of cells was increased in the cotinine aliquots supplemented with quercetin after 180 min of exposure when compared with cotinine only treated group. Conclusion: This study indicates that the ameliorating ability of quercetin on cotinine-induced decline in sperm function is associated with increased number of viable cells.

This paper proposes a unified energy-based modeling and energy-aware control paradigm for robotic systems. The paradigm is inspired by the layered and distributed control system of organisms, and uses the fundamental notion of energy in a system and the energy exchange between systems during interaction. A universal framework that models actuated and interacting robotic systems is proposed, which is used as the basis for energy-based and energy-limited control. The proposed controllers act on certain energy budgets to accomplish a desired task, and decrease performance if a budget has been depleted. These budgets ensure that a maximum amount of energy can be used, to ensure passivity and stability of the system. Experiments show the validity of the approach.

Background: Despite multidisciplinary treatment approaches, the prognosis for patients with high-grade glioma (HGG) is poor, with a median overall survival (OS) of 14.6 months for glioblastoma multiforme (GB). As high levels of vascular endothelial growth factor A (VEGF) are found in HGG, targeted anti-antiangiogenic therapy using the humanized monoclonal antibody bevacizumab (BEV) was studied in a series of clinical trials. Still, the discrepancy of BEV’s efficacy with regard to initial clinical and radiological response and its reported failure to prolong survival remains to be explained. Here, we illustrate the effectiveness of BEV in recurrent HGG by summarizing our single-centre experience. Methods: We have retrospectively investigated the effect of BEV in temozolomide refractory HGG in 39 patients treated at the University Hospital of Ulm, Germany. Results: Median duration of BEV treatment was 12.5 weeks; 23% of patients received BEV for more than 6 months and 15% for more than 1 year, until clinical or radiological tumour progression led to discontinuation. Furthermore, Karnofsky performance status increased in 30.6% and steroid dose decreased in 39% of all patients. Conclusions: The review of literature reveals that phase II and III studies support BEV as an effective therapy in recurrent HGG, at least with regard to progression-free survival (PFS), but landmark phase III trials failed to prove benefit concerning OS. Here, we discuss reasons that may account for this observation. We conclude that prolonging PFS with maintenance of neurological function and personal and economic independency justifies the off-label use of BEV.

Osteosarcoma of the foot is a very rare presentation of a rare tumor entity. In a retrospective analysis, we investigated tumor- and treatment-related variables and outcome of patients registered in the Cooperative Osteosarcoma Study Group (COSS) database between January 1980 and April 2016 who suffered from primary high-grade osteosarcoma of the foot. Among the 23 eligible patients, median age was 32 years (range: 6–58 years), 10 were female, and 13 were male. The tarsus was the most commonly affected site (n=16). Three patients had primary metastases. All patients were operated: 5 underwent primary surgery and 18 received surgery following preoperative chemotherapy. In 21 of the 23 patients, complete surgical remission was achieved. In 4 of 17 patients, a poor response to neoadjuvant chemotherapy was observed in the resected primary tumors. Median follow-up was 4.2 years (range: 0.4–18.5). At the last follow-up, 15 of the 23 patients were alive and 8 had died. Five-year overall and event-free survival estimates were 64% (standard error (SE) 12%) and 54% (SE 13%), which is similar to that observed for osteosarcoma in general. Event-free and overall survival correlated with primary metastatic status and completeness of surgery. Our findings show that high-grade osteosarcoma in the foot has a similar outcome as osteosarcoma of other sites.

Spermatozoa are highly specialized cells. Adenosine triphosphate (ATP), which provides the energy for supporting the key functions of the spermatozoa, is formed by 2 metabolic pathways, namely glycolysis and oxidative phosphorylation (OXPHOS). It is produced in the mitochondria through OXPHOS as well as in the head and principal piece of the flagellum through glycolysis. However, there is a great discrepancy as to which method of ATP production is primarily utilized by the spermatozoa for successful fertilization. Mitochondrial respiration is considered to be a more efficient metabolic process for ATP synthesis in comparison to glycolysis. However, studies have shown that the diffusion potential of ATP from the mitochondria to the distal end of the flagellum is not sufficient to support sperm motility, suggesting that glycolysis in the tail region is the preferred pathway for energy production. It is suggested by many investigators that although glycolysis forms the major source of ATP along the flagellum, energy required for sperm motility is mainly produced during mitochondrial respiration. Nevertheless, some studies have shown that when glycolysis is inhibited, proper functioning and motility of spermatozoa remains intact although it is unclear whether such motility can be sustained for prolonged periods of time, or is sufficiently vigorous to achieve optimal fertilization. The purpose of this article is to provide an overview of mammalian sperm energy metabolism and identify the preferred metabolic pathway for ATP generation which forms the basis of energy production in human spermatozoa during fertilization.