An aggregated mitochondrial distribution in preimplantation embryos disrupts nuclear morphology, function, and developmental potential.

A dispersed cytoplasmic distribution of mitochondria is a hallmark of normal cellular organization. Here, we have utilized the expression of exogenous Trak2 in mouse oocytes and embryos to disrupt the dispersed distribution of mitochondria by driving them into a large cytoplasmic aggregate. Our findings reveal that aggregated mitochondria have minimal impact on asymmetric meiotic cell divisions of the oocyte. In contrast, aggregated mitochondria during the first mitotic division result in daughter cells with unequal sizes and increased micronuclei. Further, in two-cell embryos, microtubule-mediated centering properties of the mitochondrial aggregate prevent nuclear centration, distort nuclear shape, and inhibit DNA synthesis and the onset of embryonic transcription. These findings demonstrate the motor protein-mediated distribution of mitochondria throughout the cytoplasm is highly regulated and is an essential feature of cytoplasmic organization to ensure optimal cell function.

Dynamics of Mitochondrial DNA Copy Number and Membrane Potential in Mouse Pre-Implantation Embryos: Responses to Diverse Types of Oxidative Stress.

Mitochondria undergo a myriad of changes during pre-implantation embryo development, including shifts in activity levels and mitochondrial DNA (mtDNA) replication. However, how these distinct aspects of mitochondrial function are linked and their responsiveness to diverse stressors is not well understood. Here, we show that mtDNA content increased between 8-cell embryos and the blastocyst stage, with similar copy numbers per cell in the inner cell mass (ICM) and trophectoderm (TE). In contrast, mitochondrial membrane potential (MMP) was higher in TE than ICM. Culture in ambient oxygen (20% O2) altered both aspects of mitochondrial function: the mtDNA copy number was upregulated in ICM, while MMP was diminished in TE. Embryos cultured in 20% O2 also exhibited delayed development kinetics, impaired implantation, and reduced mtDNA levels in E18 fetal liver. A model of oocyte mitochondrial stress using rotenone showed only a modest effect on on-time development and did not alter the mtDNA copy number in ICM; however, following embryo transfer, mtDNA was higher in the fetal heart. Lastly, endogenous mitochondrial dysfunction, induced by maternal age and obesity, altered the blastocyst mtDNA copy number, but not within the ICM. These results demonstrate that mitochondrial activity and mtDNA content exhibit cell-specific changes and are differentially responsive to diverse types of oxidative stress during pre-implantation embryogenesis.

Yoga Meets Intelligent Internet of Things: Recent Challenges and Future Directions.

The physical and mental health of people can be enhanced through yoga, an excellent form of exercise. As part of the breathing procedure, yoga involves stretching the body organs. The guidance and monitoring of yoga are crucial to ripe the full benefits of it, as wrong postures possess multiple antagonistic effects, including physical hazards and stroke. The detection and monitoring of the yoga postures are possible with the Intelligent Internet of Things (IIoT), which is the integration of intelligent approaches (machine learning) and the Internet of Things (IoT). Considering the increment in yoga practitioners in recent years, the integration of IIoT and yoga has led to the successful implementation of IIoT-based yoga training systems. This paper provides a comprehensive survey on integrating yoga with IIoT. The paper also discusses the multiple types of yoga and the procedure for the detection of yoga using IIoT. Additionally, this paper highlights various applications of yoga, safety measures, various challenges, and future directions. This survey provides the latest developments and findings on yoga and its integration with IIoT.

Polo-like kinase 1 promotes Cdc42-induced actin polymerization for asymmetric division in oocytes.

Polo-like kinase I (Plk1) is a highly conserved seronine/threonine kinase essential in meiosis and mitosis for spindle formation and cytokinesis. Here, through temporal application of Plk1 inhibitors, we identify a new role for Plk1 in the establishment of cortical polarity essential for highly asymmetric cell divisions of oocyte meiosis. Application of Plk1 inhibitors in late metaphase I abolishes pPlk1 from spindle poles and prevents the induction of actin polymerization at the cortex through inhibition of local recruitment of Cdc42 and Neuronal Wiskott-Aldrich Syndrome protein (N-WASP). By contrast, an already established polar actin cortex is insensitive to Plk1 inhibitors, but if the polar cortex is first depolymerized, Plk1 inhibitors completely prevent its restoration. Thus, Plk1 is essential for establishment but not maintenance of cortical actin polarity. These findings indicate that Plk1 regulates recruitment of Cdc42 and N-Wasp to coordinate cortical polarity and asymmetric cell division.

Spatiotemporal regulation of maternal mRNAs during vertebrate oocyte meiotic maturation.

Vertebrate oocytes face a particular challenge concerning the regulation of gene expression during meiotic maturation. Global transcription becomes quiescent in fully grown oocytes, remains halted throughout maturation and fertilization, and only resumes upon embryonic genome activation. Hence, the oocyte meiotic maturation process is largely regulated by protein synthesis from pre-existing maternal messenger RNAs (mRNAs) that are transcribed and stored during oocyte growth. Rapidly developing genome-wide techniques have greatly expanded our insights into the global translation changes and possible regulatory mechanisms during oocyte maturation. The storage, translation, and processing of maternal mRNAs are thought to be regulated by factors interacting with elements in the mRNA molecules. Additionally, posttranscriptional modifications of mRNAs, such as methylation and uridylation, have recently been demonstrated to play crucial roles in maternal mRNA destabilization. However, a comprehensive understanding of the machineries that regulate maternal mRNA fate during oocyte maturation is still lacking. In particular, how the transcripts of important cell cycle components are stabilized, recruited at the appropriate time for translation, and eliminated to modulate oocyte meiotic progression remains unclear. A better understanding of these mechanisms will provide invaluable insights for the preconditions of developmental competence acquisition, with important implications for the treatment of infertility. This review discusses how the storage, localization, translation, and processing of oocyte mRNAs are regulated, and how these contribute to oocyte maturation progression.

Comparison of Low-Value Care Among Commercial and Medicaid Enrollees.

BACKGROUND: Low-value healthcare is costly and inefficient and may adversely affect patient outcomes. Despite increases in low-value service use, little is known about how the receipt of low-value care differs across payers. OBJECTIVE: To evaluate differences in the use of low-value care between patients with commercial versus Medicaid coverage. DESIGN: Retrospective observational analysis of the 2017 Rhode Island All-payer Claims Database, estimating the probability of receiving each of 14 low-value services between commercial and Medicaid enrollees, adjusting for patient sociodemographic and clinical characteristics. Ensemble machine learning minimized the possibility of model misspecification. PARTICIPANTS: Medicaid and commercial enrollees aged 18-64 with continuous coverage and an encounter at which they were at risk of receiving a low-value service. INTERVENTION: Enrollment in Medicaid or Commercial insurance. MAIN MEASURES: Use of one of 14 validated measures of low-value care. KEY RESULTS: Among 110,609 patients, Medicaid enrollees were younger, had more comorbidities, and were more likely to be female than commercial enrollees. Medicaid enrollees had higher rates of use for 7 low-value care measures, and those with commercial coverage had higher rates for 5 measures. Across all measures of low-value care, commercial enrollees received more (risk difference [RD] 6.8 percentage points; CI: 6.6 to 7.0) low-value services than their counterparts with Medicaid. Commercial enrollees were also more likely to receive low-value services typically performed in the emergency room (RD 11.4 percentage points; CI: 10.7 to 12.2) and services that were less expensive (RD 15.3 percentage points; CI 14.6 to 16.0). CONCLUSION: Differences in the provision of low-value care varied across measures, though average use was slightly higher among commercial than Medicaid enrollees. This difference was more pronounced for less expensive services indicating that financial incentives may not be the sole driver of low-value care.

A Novel Smart Belt for Anxiety Detection, Classification, and Reduction Using IIoMT on Students' Cardiac Signal and MSY.

The prevalence of anxiety among university students is increasing, resulting in the negative impact on their academic and social (behavioral and emotional) development. In order for students to have competitive academic performance, the cognitive function should be strengthened by detecting and handling anxiety. Over a period of 6 weeks, this study examined how to detect anxiety and how Mano Shakti Yoga (MSY) helps reduce anxiety. Relying on cardiac signals, this study follows an integrated detection-estimation-reduction framework for anxiety using the Intelligent Internet of Medical Things (IIoMT) and MSY. IIoMT is the integration of Internet of Medical Things (wearable smart belt) and machine learning algorithms (Decision Tree (DT), Random Forest (RF), and AdaBoost (AB)). Sixty-six eligible students were selected as experiencing anxiety detected based on the results of self-rating anxiety scale (SAS) questionnaire and a smart belt. Then, the students were divided randomly into two groups: experimental and control. The experimental group followed an MSY intervention for one hour twice a week, while the control group followed their own daily routine. Machine learning algorithms are used to analyze the data obtained from the smart belt. MSY is an alternative improvement for the immune system that helps reduce anxiety. All the results illustrate that the experimental group reduced anxiety with a significant (p < 0.05) difference in group × time interaction compared to the control group. The intelligent techniques achieved maximum accuracy of 80% on using RF algorithm. Thus, students can practice MSY and concentrate on their objectives by improving their intelligence, attention, and memory.

Miro1 depletion disrupts spatial distribution of mitochondria and leads to oocyte maturation defects.

Mitochondria are dynamic organelles that undergo regulated microtubule- and actin-mediated trafficking to meet local energy and metabolic needs. Mitochondrial trafficking may be particularly critical in large cells such as eggs and early embryos where spindle formation and polar body extrusion occur in specific regions of the cytoplasm. To investigate the role of mitochondrial distribution in oocytes we have targeted the mitochondrial membrane protein, MIRO1, which couples mitochondria to the motor protein-TRAK complex. Oocyte-specific deletion of MIRO1 leads to the formation of large aggregates of mitochondria in perinuclear and cortical compartments. Mitochondria remain capable of long-range trafficking during maturation, indicating redundancy in the mechanisms coupling mitochondria to motor proteins. Polar body extrusion in the absence of MIRO1 was reduced by approximately 20%. In MIRO1-deleted zygotes, mitochondria showed increased accumulation around the pronuclei but this did not affect mitochondrial distribution to daughter blastomeres. In vitro development of parthenogenetic embryos was also reduced, although no differences were found in the fertility of oocyte-specific Miro1 KO mice. These findings demonstrate MIRO1 acts as a mitochondrial adaptor, setting mitochondrial distribution in oocytes and early embryos, and disrupting this process compromises in vitro oocyte maturation and embryo development.

Early-Stage Alzheimer's Disease Categorization Using PET Neuroimaging Modality and Convolutional Neural Networks in the 2D and 3D Domains.

Alzheimer's Disease (AD) is a health apprehension of significant proportions that is negatively impacting the ageing population globally. It is characterized by neuronal loss and the formation of structures such as neurofibrillary tangles and amyloid plaques in the early as well as later stages of the disease. Neuroimaging modalities are routinely used in clinical practice to capture brain alterations associated with AD. On the other hand, deep learning methods are routinely used to recognize patterns in underlying data distributions effectively. This work uses Convolutional Neural Network (CNN) architectures in both 2D and 3D domains to classify the initial stages of AD into AD, Mild Cognitive Impairment (MCI) and Normal Control (NC) classes using the positron emission tomography neuroimaging modality deploying data augmentation in a random zoomed in/out scheme. We used novel concepts such as the blurring before subsampling principle and distant domain transfer learning to build 2D CNN architectures. We performed three binaries, that is, AD/NC, AD/MCI, MCI/NC and one multiclass classification task AD/NC/MCI. The statistical comparison revealed that 3D-CNN architecture performed the best achieving an accuracy of 89.21% on AD/NC, 71.70% on AD/MCI, 62.25% on NC/MCI and 59.73% on AD/NC/MCI classification tasks using a five-fold cross-validation hyperparameter selection approach. Data augmentation helps in achieving superior performance on the multiclass classification task. The obtained results support the application of deep learning models towards early recognition of AD.

Depletion of oocyte dynamin-related protein 1 shows maternal-effect abnormalities in embryonic development.

Eggs contain about 200,000 mitochondria that generate adenosine triphosphate and metabolites essential for oocyte development. Mitochondria also integrate metabolism and transcription via metabolites that regulate epigenetic modifiers, but there is no direct evidence linking oocyte mitochondrial function to the maternal epigenome and subsequent embryo development. Here, we have disrupted oocyte mitochondrial function via deletion of the mitochondrial fission factor Drp1. Fission-deficient oocytes exhibit a high frequency of failure in peri- and postimplantation development. This is associated with altered mitochondrial function, changes in the oocyte transcriptome and proteome, altered subcortical maternal complex, and a decrease in oocyte DNA methylation and H3K27me3. Transplanting pronuclei of fertilized Drp1 knockout oocytes to normal ooplasm fails to rescue embryonic lethality. We conclude that mitochondrial function plays a role in establishing the maternal epigenome, with serious consequences for embryo development.

Taxifolin as a Major Bioactive Compound in the Vasorelaxant Effect of Different Pigmented Rice Bran Extracts.

Cardiovascular disease is one of the leading causes of morbidity and mortality in recent years. The intake of polyphenol rich diets has been associated with improved cardiovascular function and reduced cardiovascular risks. Oryza sativa L. is one of the most common cereals worldwide. Rice bran, a byproduct of the rice milling process, contains many bioactive ingredients, including polyphenols, polysaccharides, proteins, and micronutrients. It is also consumed as a healthy diet in the form of rice bran oil and powder in many Asian countries like Japan, South Korea, and India for its several health benefits as a natural antioxidant. Thus, this study evaluated the vasorelaxant effect of ethanolic extracts of brown, green, red, and black rice bran and investigated its underlying vasorelaxant mechanism. Among the four rice bran extracts (RBEs) examined, the red rice bran extract (RRBE) had a strong endothelium-dependent vasorelaxant effect, which was markedly prevented by N-ω-nitro-L-arginine [endothelial nitric oxide synthase (eNOS) inhibitor], wortmannin [phosphoinositide-3 kinase (PI3K) inhibitor], and 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one (inhibitor of guanylate cyclase). Likewise, RRBE induced the phosphorylation of eNOS and Src in cultured endothelial cells, thereby stimulating NO formation. Altogether, these findings propose that RRBE induces endothelium-dependent relaxation, involving at least in part, NO-mediated signaling through the PI3K/eNOS pathway. Further, LC-PDA analysis conducted on the four RBEs also revealed that RRBE highly contained taxifolin, which is an active flavanonol that induces endothelium-dependent vasorelaxation, compared to other RBEs. Subsequently, the underlying mechanism of taxifolin was assessed through vascular reactivity studies with pharmacological inhibitors similar to that of RRBE. These findings deciphered a distinct difference in vasorelaxant effects between RRBE and the other RBEs. We also observed that RRBE induced a potent endothelium-dependent NO-mediated relaxation in coronary artery rings, which involved the Src/PI3K pathway that activates eNOS. Additionally, taxifolin exhibited, at least in part, similar vasoprotective effects of RRBE. Therefore, we propose that RRBE may serve as natural sources of functional phytochemicals that improve cardiovascular diseases associated with disturbed NO production and endothelial dysfunction.

Oocyte mitochondria-key regulators of oocyte function and potential therapeutic targets for improving fertility.

The development of oocytes and early embryos is dependent on mitochondrial ATP production. This reliance on mitochondrial activity, together with the exclusively maternal inheritance of mitochondria in development, places mitochondria as central regulators of both fertility and transgenerational inheritance mechanisms. Mitochondrial mass and mtDNA content massively increase during oocyte growth. They are highly dynamic organelles and oocyte maturation is accompanied by mitochondrial trafficking around subcellular compartments. Due to their key roles in generation of ATP and reactive oxygen species (ROS), oocyte mitochondrial defects have largely been linked with energy deficiency and oxidative stress. Pharmacological treatments and mitochondrial supplementation have been proposed to improve oocyte quality and fertility by enhancing ATP generation and reducing ROS levels. More recently, the role of mitochondria-derived metabolites in controlling epigenetic modifiers has provided a mechanistic basis for mitochondria-nuclear crosstalk, allowing adaptation of gene expression to specific metabolic states. Here, we discuss the multi-faceted mechanisms by which mitochondrial function influence oocyte quality, as well as longer-term developmental events within and across generations.

HENMT1 is involved in the maintenance of normal female fertility in the mouse.

PIWI-interacting small RNAs (piRNAs) maintain genome stability in animal germ cells, with a predominant role in silencing transposable elements. Mutations in the piRNA pathway in the mouse uniformly lead to failed spermatogenesis and male sterility. By contrast, mutant females are fertile. In keeping with this paradigm, we previously reported male sterility and female fertility associated with loss of the enzyme HENMT1, which is responsible for stabilising piRNAs through the catalysation of 3'-terminal 2'-O-methylation. However, the Henmt1 mutant females were poor breeders, suggesting they could be subfertile. Therefore, we investigated oogenesis and female fertility in these mice in greater detail. Here, we show that mutant females indeed have a 3- to 4-fold reduction in follicle number and reduced litter sizes. In addition, meiosis-II mutant oocytes display various spindle abnormalities and have a dramatically altered transcriptome which includes a down-regulation of transcripts required for microtubule function. This down-regulation could explain the spindle defects observed with consequent reductions in litter size. We suggest these various effects on oogenesis could be exacerbated by asynapsis, an apparently universal feature of piRNA mutants of both sexes. Our findings reveal that loss of the piRNA pathway in females has significant functional consequences.

Association of Inclusion of Medicare Advantage Patients in Hospitals' Risk-Standardized Readmission Rates, Performance, and Penalty Status.

Importance: The Hospital Readmissions Reduction Program publicly reports and financially penalizes hospitals according to 30-day risk-standardized readmission rates (RSRRs) exclusively among traditional Medicare (TM) beneficiaries but not persons with Medicare Advantage (MA) coverage. Exclusively reporting readmission rates for the TM population may not accurately reflect hospitals' readmission rates for older adults. Objective: To examine how inclusion of MA patients in hospitals' performance is associated with readmission measures and eligibility for financial penalties. Design, Setting, and Participants: This is a retrospective cohort study linking the Medicare Provider Analysis and Review file with the Healthcare Effectiveness Data and Information Set at 4070 US acute care hospitals admitting both TM and MA patients. Participants included patients admitted and discharged alive with a diagnosis of acute myocardial infarction (AMI), congestive heart failure (CHF), or pneumonia between 2011 and 2015. Data analyses were conducted between April 1, 2018, and November 20, 2020. Exposures: Admission to an acute care hospital. Main Outcomes and Measures: The outcome was readmission for any reason occurring within 30 days after discharge. Each hospital's 30-day RSRR was computed on the basis of TM, MA, and all patients and estimated changes in hospitals' performance and eligibility for financial penalties after including MA beneficiaries for calculating 30-day RSRRs. Results: There were 748 033 TM patients (mean [SD] age, 76.8 [83] years; 360 692 [48.2%] women) and 295 928 MA patients (mean [SD] age, 77.5 [7.9] years; 137 422 [46.4%] women) hospitalized and discharged alive for AMI; 1 327 551 TM patients (mean [SD] age, 81 [8.3] years; 735 855 [55.4%] women) and 457 341 MA patients (mean [SD] age, 79.8 [8.1] years; 243 503 [53.2%] women) for CHF; and 2 017 020 TM patients (mean [SD] age, 80.7 [8.5] years; 1 097 151 [54.4%] women) and 610 790 MA patients (mean [SD] age, 79.6 [8.2] years; 321 350 [52.6%] women) for pneumonia. The 30-day RSRRs for TM and MA patients were correlated (correlation coefficients, 0.31 for AMI, 0.40 for CHF, and 0.41 for pneumonia) and the TM-based RSRR systematically underestimated the RSRR for all Medicare patients for each condition. Of the 2820 hospitals with 25 or more admissions for at least 1 of the outcomes of AMI, CHF, and pneumonia, 635 (23%) had a change in their penalty status for at least 1 of these conditions after including MA data. Changes in hospital performance and penalty status with the inclusion of MA patients were greater for hospitals in the highest quartile of MA admissions. Conclusions and Relevance: In this cohort study, the inclusion of data from MA patients changed the penalty status of a substantial fraction of US hospitals for at least 1 of 3 reported conditions. This suggests that policy makers should consider including all hospital patients, regardless of insurance status, when assessing hospital quality measures.

Mitochondria-targeted therapeutics, MitoQ and BGP-15, reverse aging-associated meiotic spindle defects in mouse and human oocytes.

STUDY QUESTION: Do mitochondria-targeted therapies reverse ageing- and oxidative stress-induced spindle defects in oocytes from mice and humans? SUMMARY ANSWER: Exposure to MitoQ or BGP-15 during IVM protected against spindle and chromosomal defects in mouse oocytes exposed to oxidative stress or derived from reproductively aged mice whilst MitoQ promoted nuclear maturation and protected against chromosomal misalignments in human oocytes. WHAT IS KNOWN ALREADY: Spindle and chromosomal abnormalities in oocytes are more prevalent with maternal aging, increasing the risk of aneuploidy, miscarriage and genetic disorders such as Down's syndrome. The origin of compromised oocyte function may be founded in mitochondrial dysfunction and increased reactive oxygen species (ROS). STUDY DESIGN, SIZE, DURATION: Oocytes from young and old mice were treated with MitoQ and/or BGP-15 during IVM. To directly induce mitochondrial dysfunction, oocytes were treated with H2O2, and then treated the MitoQ and/or BGP-15. Immature human oocytes were cultured with or without MitoQ. Each experiment was repeated at least three times, and data were analyzed by unpaired-sample t-test or chi-square test. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immature germinal vesicle (GV) stage oocytes from 1-, 12- and 18-month-old mice were obtained from preovulatory ovarian follicles. Oocytes were treated with MitoQ and/or BGP-15 during IVM. GV-stage human oocytes were cultured with or without MitoQ. Mitochondrial membrane potential and mitochondrial ROS were measured by live-cell imaging. Meiotic spindle and chromosome alignments were visualized by immunofluorescent labeling of fixed oocytes and the 3-dimensional images were analyzed by Imaris. MAIN RESULTS AND THE ROLE OF CHANCE: MitoQ or BGP-15 during IVM protects against spindle and chromosomal defects in oocytes exposed to oxidative stress and in oocytes from aged mice (P < 0.001). In human oocytes, the presence of MitoQ during IVM promoted nuclear maturation and had a similar positive effect in protecting against chromosomal misalignments (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Our study identifies two excellent candidates that may help to improve fertility in older women. However, these potential therapies must be tested for efficacy in clinical IVM systems, and undergo thorough examination of resultant offspring in preclinical models before utilization. WIDER IMPLICATIONS OF THE FINDINGS: Our results using in-vitro systems for oocyte maturation in both mouse and human provide proof of principle that mitochondrially targeted molecules such as MitoQ and BGP-15 may represent a novel therapeutic approach against maternal aging-related spindle and chromosomal abnormalities. STUDY FUNDING/COMPETING INTEREST(S): The project was financially supported by the National Health and Medical Research Council and Australian Research Council, Australia. U.A.-Z. was supported by the Iraqi Higher Education and Scientific Research Ministry PhD scholarship and O.C. was supported by TUBITAK-1059B191601275. M.P.M. consults for MitoQ Inc. and holds patents in mitochondria-targeted therapies. R.L.R. is an inventor on patents relating to the use of BGP-15 to improve gamete quality. TRIAL REGISTRATION NUMBER: N/A.

Moderate Hydronephrosis among Acute Ureteral Calculus on Ultrasonographic Imaging in a Tertiary Care Center in Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: Ureteric calculi are lying at any point of ureter from the pelvic ureteric junction to the vesicoureteral junction. If left untreated, ureteropelvic junction obstruction can lead to hydronephrosis. With the improved availability of computed tomography and ultrasound scanning, hydronephrosis is being diagnosed more frequently. The main aim of this study is to find out the prevalence of moderate Hydronephrosis among ureteral calculus on ultrasonography imaging in a tertiary care center of Nepal. METHODS: A descriptive cross-sectional study was conducted among 110 acute ureteral calculus cases at Radiodiagnosis and Imaging Department of Chitwan Medical College and Teaching Hospital, Bharatpur from 15th August 2020 to 15th May 2021. The ethical approval was taken from the Institutional Review Committee of same institution. Convenient sampling technique was used to select the participant. The collected data was entered in excel 16 and analysed in Statistical Package for Social Sciences. Point estimate at 95% Confidence Interval was done and frequency and percentage were calculated. RESULTS: Out of the 110 cases of acute ureteral calculus, 31 (28.2%) (19.79-36.60 at 95% Confidence Interval) has moderate hydronephrosis in the ultrasonographic imaging. The mean age of participants was 31.61±8.51 years and male to female ratio was 1.97:1. Vesicoureteric junction was the most common site for ureteric calculus 39 (35.5%). CONCLUSIONS: The ultrasound is an easy method to be applied, and a fast one to help and diagnose obstructive hydronephrosis. The main causes of hydronephrosis are kidney stones, followed by ureteral stones, with a moderate degree of hydronephrosis.

Vasorelaxant Effect of Boesenbergia rotunda and Its Active Ingredients on an Isolated Coronary Artery.

Cardiovascular diseases are a major cause of death in developed countries. The regulation of vascular tone is a major approach to prevent and ameliorate vascular diseases. As part of our ongoing screening for cardioprotective natural compounds, we investigated the vasorelaxant effect of rhizomes from Boesenbergia rotunda (L.) Mansf. [Boesenbergia pandurata (Roxb.) Schltr.] used as a spice and herbal medicine in Asian countries. The methanol extract of B. rotunda rhizomes (BRE) exhibited significant vasorelaxation effects ex vivo at EC50 values of 13.4 ± 6.1 µg/mL and 40.9 ± 7.9 µg/mL, respectively, with and without endothelium in the porcine coronary artery ring. The intrinsic mechanism was evaluated by treating with specific inhibitors or activators that typically affect vascular reactivity. The results suggested that BRE induced relaxation in the coronary artery rings via an endothelium-dependent pathway involving NO-cGMP, and also via an endothelium-independent pathway involving the blockade of Ca2+ channels. Vasorelaxant principles in BRE were identified by subsequent chromatographic methods, which revealed that flavonoids regulate vasorelaxant activity in BRE. One of the flavonoids was a Diels-Alder type adduct, 4-hydroxypanduratin A, which showed the most potent vasorelaxant effect on porcine coronary artery with an EC50 of 17.8 ± 2.5 µM. Our results suggest that rhizomes of B. rotunda might be of interest as herbal medicine against cardiovascular diseases.

Prevention of Fine Dust-Induced Vascular Senescence by Humulus lupulus Extract and Its Major Bioactive Compounds.

Both short- and long-term exposure to fine dust (FD) from air pollution has been linked to various cardiovascular diseases (CVDs). Endothelial cell (EC) senescence is an important risk factor for CVDs, and recent evidence suggests that FD-induced premature EC senescence increases oxidative stress levels. Hop plant (Humulus lupulus) is a very rich source of polyphenols known to have nutritional and therapeutic properties, including antioxidant behavior. The aims of this study were to evaluate whether Humulus lupulus extract prevents FD-induced vascular senescence and dysfunction and, if so, to characterize the underlying mechanisms and active components. Porcine coronary arteries and endothelial cells were treated with FD in the presence or absence of hop extract (HOP), and the senescence-associated-beta galactosidase (SA-ß-gal) activity, cell-cycle progression, expression of senescence markers, oxidative stress level, and vascular function were evaluated. Results indicated that HOP inhibited FD-induced SA-ß-gal activity, cell-cycle arrest, and oxidative stress, suggesting that HOP prevents premature induction of senescence by FD. HOP also ameliorated FD-induced vascular dysfunction. Additionally, xanthohumol (XN) and isoxanthohumol (IX) were found to produce the protective effects of HOP. Treatment with HOP and its primary active components XN and IX downregulated the expression of p22phox, p53, and angiotensin type 1 receptor, which all are known FD-induced redox-sensitive EC senescence inducers. Taken together, HOP and its active components protect against FD-induced endothelial senescence most likely via antioxidant activity and may be a potential therapeutic agent for preventing and/or treating air-pollution-associated CVDs.

Insights into Gonadal Sex Differentiation Provided by Single-Cell Transcriptomics in the Chicken Embryo.

Although the genetic triggers for gonadal sex differentiation vary across species, the cell biology of gonadal development was long thought to be largely conserved. Here, we present a comprehensive analysis of gonadal sex differentiation, using single-cell sequencing in the embryonic chicken gonad during sexual differentiation. The data show that chicken embryonic-supporting cells do not derive from the coelomic epithelium, in contrast to other vertebrates studied. Instead, they derive from a DMRT1+/PAX2+/WNT4+/OSR1+ mesenchymal cell population. We find a greater complexity of gonadal cell types than previously thought, including the identification of two distinct sub-populations of Sertoli cells in developing testes and derivation of embryonic steroidogenic cells from a differentiated supporting-cell lineage. Altogether, these results indicate that, just as the genetic trigger for sex differs across vertebrate groups, cell lineage specification in the gonad may also vary substantially.