Effect of various antioxidants on ovarian tissue vitrification success in sheep.

BACKGROUND: Vitrification is a technique of cryopreservation that has been proposed as a promising alternative method for the preservation of oocytes, embryos and gonadal tissue. OBJECTIVE: To determine the effect of different antioxidants on post-thaw viability, morphology of retrieved oocytes and histology of vitrified ovarian tissue. MATERIALS AND METHODS: Four different antioxidants [i.e., resveratrol (20 uM), ZnSO4 (500 uM), curcumin (25 uM) and quercetin (1 uM)] were evaluated after their addition to the vitrification and warming media for their effects on the viability and morphology of retrieved oocytes and the histology of vitrified ovarian tissue. RESULTS: The number of oocytes retrieved from ovarian tissue from the above mentioned antioxidants and vitrified control were 34, 41, 26, 31 and 46 respectively. Among these the number of viable oocytes were found to be 24 (70.6%), 30 (73.1 %), 20 (76.9%), 26 (83.9%) and 33 (71.7%) and the number of oocytes found morphologically normal were 24 (70.6%), 26 (63.4%), 18 (69.2%), 21 (67.7%) and 34 (73.9%) for the above mentioned different antioxidants and vitrified control, respectively. Non-significant (P. > 0.05) differences were found between different treatment groups. Histomorphological evaluation of the ovarian cortical tissue showed that the percentage of intact follicles was significantly (P < 0.05) higher in the fresh control (84.19±3.9) than in other groups. Non-significant differences were found between resveratrol (50.2±5.5), curcumin (48.7±5.7), quercetin (51.6±4.8) and the vitrified control (42.7±6.1) groups; however, the ZnSO4 supplemented group (23.1±8.54) differed significantly (P < 0.05) from other antioxidant groups but was non-significant (P > 0.05) with the vitrified control group (42.7±6.1). CONCLUSION: The addition of antioxidants resveratrol, curcumin and quercetin at these concentrations tended to non-significantly improve the follicular integrity after vitrification. Doi.org/10.54680/fr24410110212.

Emergence of CuInS2 derived photocatalyst for environmental remediation and energy conversion.

Hydrogen production, catalytic organic synthesis, carbon dioxide reduction, environmental purification, and other major fields have all adopted photocatalytic technologies due to their eco-friendliness, ease of use, and reliance on sunlight as the driving force. Photocatalyst is the key component of photocatalytic technology. Thus, it is of utmost importance to produce highly efficient, stable, visible-light-responsive photocatalysts. CIS stands out among other visible-light-response photocatalysts for its advantageous combination of easy synthesis, non-toxicity, high stability, and suitable band structure. In this study, we took a brief glance at the synthesis techniques for CIS after providing a quick introduction to the fundamental semiconductor features, including the crystal and band structures of CIS. Then, we discussed the ways doping, heterojunction creation, p-n heterojunction, type-II heterojunction, and Z-scheme may be used to modify CIS's performance. Subsequently, the applications of CIS towards pollutant degradation, CO2 reduction, water splitting, and other toxic pollutants remediation are reviewed in detail. Finally, several remaining problems with CIS-based photocatalysts are highlighted, along with future potential for constructing more superior photocatalysts.

Size-Dependent Dispersion of Rhodium Clusters into Isolated Single Atoms at Low Temperature and the Consequences for CO Oxidation Activity.

Understanding the dynamic structural evolution of supported metal clusters under reaction conditions is crucial to develop structure reactivity relations. Here, we followed the structure of different size Rh clusters supported on Al2 O3 using in situ/operando spectroscopy and ex situ aberration-corrected electron microscopy. We report a dynamic evolution of rhodium clusters into thermally stable isolated single atoms upon exposure to oxygen and during CO oxidation. Rh clusters partially disperse into single atoms at room temperature and the extent of dispersion increases as the Rh size decreases and as the reaction temperature increases. A strong correlation is found between the extent of dispersion and the CO oxidation kinetics. More importantly, dispersing Rh clusters into single atoms increases the activity at room temperature by more than two orders of magnitude due to the much lower activation energy on single atoms (40 vs. 130 kJ/mol). This work demonstrates that the structure and reactivity of small Rh clusters are very sensitive to the reaction environment.

Chronic delta-9-tetrahydrocannabinol (THC) treatment counteracts SIV-induced modulation of proinflammatory microRNA cargo in basal ganglia-derived extracellular vesicles.

BACKGROUND: Early invasion of the central nervous system (CNS) by human immunodeficiency virus (HIV) (Gray et al. in Brain Pathol 6:1-15, 1996; An et al. in Ann Neurol 40:611-6172, 1996), results in neuroinflammation, potentially through extracellular vesicles (EVs) and their micro RNAs (miRNA) cargoes (Sharma et al. in FASEB J 32:5174-5185, 2018; Hu et al. in Cell Death Dis 3:e381, 2012). Although the basal ganglia (BG) is a major target and reservoir of HIV in the CNS (Chaganti et al. in Aids 33:1843-1852, 2019; Mintzopoulos et al. in Magn Reson Med 81:2896-2904, 2019), whether BG produces EVs and the effect of HIV and/or the phytocannabinoid-delta-9-tetrahydrocannabinol (THC) on BG-EVs and HIV neuropathogenesis remain unknown. METHODS: We used the simian immunodeficiency virus (SIV) model of HIV and THC treatment in rhesus macaques (Molina et al. in AIDS Res Hum Retroviruses 27:585-592, 2011) to demonstrate for the first time that BG contains EVs (BG-EVs), and that BG-EVs cargo and function are modulated by SIV and THC. We also used primary astrocytes from the brains of wild type (WT) and CX3CR1+/GFP mice to investigate the significance of BG-EVs in CNS cells. RESULTS: Significant changes in BG-EV-associated miRNA specific to SIV infection and THC treatment were observed. BG-EVs from SIV-infected rhesus macaques (SIV EVs) contained 11 significantly downregulated miRNAs. Remarkably, intervention with THC led to significant upregulation of 37 miRNAs in BG-EVs (SIV-THC EVs). Most of these miRNAs are predicted to regulate pathways related to inflammation/immune regulation, TLR signaling, Neurotrophin TRK receptor signaling, and cell death/response. BG-EVs activated WT and CX3CR1+/GFP astrocytes and altered the expression of CD40, TNFα, MMP-2, and MMP-2 gene products in primary mouse astrocytes in an EV and CX3CR1 dependent manners. CONCLUSIONS: Our findings reveal a role for BG-EVs as a vehicle with potential to disseminate HIV- and THC-induced changes within the CNS.

Molecular determination of progesterone receptor's PROGINS allele (Alu insertion) and its association with the predisposition and susceptibility to polycystic ovary syndrome (PCOS).

Polycystic ovary syndrome, previously known as Stein-Leventhal syndrome, is associated with altered reproductive endocrinology, predisposing a young woman towards the risk of PCOS. It has a prevalence of 6-20% among the reproductive-age women. Progesterone is a key hormone in the pathophysiology of PCOS and patients show diminished response (progesterone resistance), implicating the role of progesterone receptor (PR) as a factor in the disease etiology and prognosis. In this case-control study, we have used mutation-specific PCR (confirmed by Sanger sequencing) to detect the presence of a pathologically significant PR polymorphic variant called as PROGINS. The variant has an Alu insertion in intron G and has two SNPs in exon 4 and exon 5, with all the three aberrations in complete disequilibrium. Our results demonstrated a statistically significant difference in the frequencies of PROGINS between the PCOS patients and healthy controls (p = 0.047). The frequencies of the genotypes CC (A1/A1), CT (A1/A2), and TT (A2/A2) in patients were 74.50%, 20.58%, and 4.90%, and in healthy controls they were 87.28%, 11%, and 1.69%, respectively. Our results put forward two determining factors with regard to PCOS: (i) the frequency of PROGINS allele was significantly higher among PCOS patients compared to the healthy matched controls (0.15 vs 0.07) in the studied population, (ii) the PROGIN allele was significantly associated with the lower levels of serum progesterone in PCOS patients (p < 0.003). The findings are conspicuous as these relate the PROGINS variant to the increased susceptibility of PCOS and might explain the progesterone resistance in patients.

Differential Response of Bacterial Microdiversity to Simulated Global Change.

Global change experiments often observe shifts in bacterial community composition based on 16S rRNA gene sequences. However, this genetic region can mask a large amount of genetic and phenotypic variation among bacterial strains sharing even identical 16S regions. As such, it remains largely unknown whether variation at the sub-16S level, sometimes termed microdiversity, responds to environmental perturbations and whether such changes are relevant to ecosystem processes. Here, we investigated microdiversity within Curtobacterium, the dominant bacterium found in the leaf litter layer of soil, to simulated drought and nitrogen addition in a field experiment. We first developed and validated Curtobacterium-specific primers of the groEL gene to assess microdiversity within this lineage. We then tracked the response of this microdiversity to simulated global change in two adjacent plant communities, grassland and coastal sage scrub (CSS). Curtobacterium microdiversity responded to drought but not nitrogen addition, indicating variation within the genus of drought tolerance but not nitrogen response. Further, the response of microdiversity to drought depended on the ecosystem, suggesting that litter substrate selects for a distinct composition of microdiversity that is constrained in its response, perhaps related to tradeoffs in resource acquisition traits. Supporting this interpretation, a metagenomic analysis revealed that the composition of Curtobacterium-encoded carbohydrate-active enzymes (CAZymes) varied distinctly across the two ecosystems. Identifying the degree to which relevant traits are phylogenetically conserved may help to predict when the aggregated response of a 16S-defined taxon masks differential responses of finer-scale bacterial diversity to global change. IMPORTANCE Microbial communities play an integral role in global biogeochemical cycling, but our understanding of how global change will affect microbial community structure and functioning remains limited. Microbiome analyses typically aggregate large amounts of genetic diversity which may obscure finer variation in traits. This study found that fine-scale diversity (or microdiversity) within the bacterial genus Curtobacterium was affected by simulated global changes. However, the degree to which this was true depended on the type of global change, as the composition of Curtobacterium microdiversity was affected by drought, but not by nitrogen addition. Further, these changes were associated with variation in carbon degradation traits. Future work might improve predictions of microbial community responses to global change by considering microdiversity.

Primary retrograde urinary drainage using image and endoscopy guidance via urostomies.

AIM: To report the technical success of image and endoscopy-guided retrograde trans-urostomy urinary drainage as a primary catheter placement method performed by interventional radiology (IR). MATERIALS AND METHODS: Nine patients (15 attempted drain placements) with ureteric obstruction following radical cystectomy and urostomy creation were included. The patients were referred to IR for urinary drainage. All patients underwent primary image and endoscopy-guided retrograde trans-urostomy urinary drainage. RESULTS: Primary image and endoscopy-guided retrograde trans-urostomy urinary drainage was successful in 13/15 (86.6%) attempts. The proposed technique had a limited complication rate omitting the percutaneous nephrostomy access step. CONCLUSION: Primary image and endoscopy guided retrograde trans-urostomy urinary drainage should be considered before percutaneous nephrostomy in all patients with a urostomy.

Thoracic aortic aneurysm repair using the elephant trunk technique and associated complications.

The frozen elephant trunk stent has greatly facilitated the repair of elective and emergency arch and proximal descending thoracic aortic aneurysms and dissections. As one of the few tertiary hospitals that routinely inserts and images the floating and frozen elephant trunk grafts, we aim to provide an up-to-date illustration of the contrasting methods of elephant trunk thoracic aortic aneurysm repair through a computed tomography (CT) review and detail the common radiological interpretation pitfalls in addition to the most significant associated complications.

Laboratory Biomarkers Associated with Severity and Mortality of COVID-19.

BACKGROUND: Corona Virus Disease 2019 (COVID-19) emerged late 2019 and has become a global pandemic. There is an urgent need for identification of biomarkers to predict severity of the disease for early treatment and to avoid mortality especially in high-risk population. Therefore, the aim of this study is to investigate laboratory results in COVID-19 patients in Saudi Arabia to identify potential biomarkers correlated with disease severity. METHODS: Clinical records of 200 patients diagnosed with COVID-19 from July to August 2020 at Jeddah East Hospital were retrospectively analyzed. Laboratory tests including coagulation parameters, D-dimer, kidney, cardiac, and liver enzymes were statistically investigated in patients admitted to wards and intensive care units (ICU). RESULTS: The majority of patients admitted to ward (156/200) were young (mean 47 years old) compared to those admitted to ICU (mean 60 years old), 14/44 passed away in the ICU. Magnesium was significantly (p < 0.05) elevated in the ICU group while blood urea nitrogen and creatinine level was significantly higher in deceased patients (p < 0.05). Lactate dehydrogenase results were high among all groups, compared to normal range, although its level significantly increased (p > 0.05) in ICU and death groups. CONCLUSIONS: Elevated lactate dehydrogenase, blood urea nitrogen and creatinine levels may increase the risk of ICU admission and death from COVID-19, which can be used as potential biomarkers for disease severity. Using these markers could help physicians choose the optimal therapeutical option and provide patients with better treatment.

Recent advancements in vitrification cryodevices for gamete and gonadal tissue.

Cryopreservation of gametes and gonadal tissue is nowadays primarily accomplished through vitrification. Variables such as cooling rate, viscosity and volume of vitrification solution are critical in gamete vitrification. In addition, sample size and stepwise exposure are also crucial for gonadal tissue vitrification. Recently a class of cryodevices has been developed to reduce the volume of vitrification solution so as to achieve higher cooling rates. Vitrification devices are classified as "open" or "closed" depending on whether the medium comes into direct contact with liquid nitrogen during the process. Examples of the open cryodevices for gamete vitrification are Cryotop, Cryolock, open pulled straw (OPS), etc., and closed devices are Vitrisafe, CryoTip, and high security vitrification kit. Similarly, for tissue vitrification open cryodevices used are needles, cryovials and closed devices used are Cryotissue, ovarian tissue cryosystem, etc. Among all the gamete cryodevices, Cryotop is unique and the best-selling micro-volume storage device. Use of this device has resulted in the highest number of babies born after embryo or oocyte vitrification. Another novel device, Kitasato vitrification system, is a vitrification solution absorber, which is similar to Cryotop but differs in one way, as it possesses a porous membrane that absorbs extra solution from the gamete. This review provides an update on the recent use of cryodevices for gamete and gonadal tissue vitrification. doi.org/10.54680/fr22310110112.

Can honey improve the quality of cryopreserved cross bred ram semen added to tris egg yolk extender?

BACKGROUND: Honey can improve the quality of cryopreserved ram semen because of its multinutrient and cryoprotective nature added to standard tris egg yolk extender. OBJECTIVE: Different concentrations of honey were added to the standard tris egg yolk extender to improve the post-thaw quality of crossbred ram semen. METHOD: Thirty six (36) ejaculates from eight healthy cross bred rams were pooled and divided into four aliquots. Standard tris egg yolk extender without any alteration acted as Control (C) and was supplemented with different concentrations of honey, viz. T1 (honey 1.5%), T2 (2.5%), and T3 (3.5%). RESULTS: The percent (mean ± S.E.M) sperm motility at pre-freeze was significantly (P < 0.05) higher in Group T2 and at post-thaw in Group T3 in comparison to T1 and C treatment groups. The percent (mean ± S.E.M) HOST reacted spermatozoa at post-thaw was significantly (P < 0.05) higher in Group C and at pre-freeze the value was significantly (P < 0.05) higher in the same treatment group than Group T1. The mean MDA level (mean ± S.E.M) at post thaw was significantly (P < 0.05) lower in Group T3 than the treatment groups C and Group T1. CONCLUSION: From this study it is concluded that the addition of 3.5% honey to the standard tris egg yolk extender provides better protection to ram semen than the addition of 1.5% honey (i.e., Control). doi.org/10.54680/fr22610110212.

Prevalence and Association of Transfusion Transmitted Infections with ABO and Rh Blood Groups among Blood Donors in the Western Region of Saudi Arabia: A 7-Year Retrospective Analysis.

This study was aimed at determining the prevalence estimate and association of transfusion-transmitted infections (TTIs) with ABO and Rh blood groups among blood donors at the King Faisal Specialist Hospital and Research Center (KFSH & RC) in the western region of Saudi Arabia. A retrospective study was conducted at the blood bank center of KFSH and RC from 1 January 2013 to 31 December 2019. Data on ABO and Rh blood group testing, serological testing, molecular investigations, serological assays, nucleic acid testing (NATs), and socio-demographic information were gathered. During the study period, there were 959,431 blood donors at the KFSH and RC. The overall 7-year cumulative prevalence estimate of blood transfusion-transmitted infections among blood donors was low at 7.93%, with an average prevalence estimate of 0.66%. Donors with the O blood group, the O RhD +ve blood group, in particular, were more at risk of developing TTIs, whereas donors with the AB blood group, the AB RhD -ve blood group, in particular, were at the lowest risk of developing TTIs. In total, 96.9% of the blood donors were males (n = 916,567). Almost half of the blood donors belong to the O blood group (49.4%). A total of 861,279 (91.0%) donors were found to be RhD positive. The percentages of TTIs were found to be higher in RhD +ve donors compared with RhD -ve donors. The prevalence estimate of the hemoglobin C (HbC) infection was the most common TTI among the blood donors being 3.97%, followed by malaria being 2.21%. The least prevalence estimate of TTI in the present study was for NAT HIV being 0.02%. Significant associations were observed between RhD +ve and RhD -ve among the malaria-infected donors (A: χ2 = 26.618, p = 0.001; AB: χ2 = 23.540, p = 0.001; B: χ2 = 5.419, p = 0.020; O: χ2 = 68.701, p = 0.001). The current 7-year retrospective study showed a low level of TTIs among blood donors. However, we urge that more research encompassing the entire country be conducted in order to obtain more representative results in terms of the prevalence estimate and association of transfusion-transmitted infections with ABO and Rh blood groups in communities.

Conflicting attitudes: Analyzing social media data to understand the early discourse on COVID-19 passports.

In several countries, vaccine passports are being encouraged to hasten the return to some form of normalcy amidst the COVID-19 pandemic. Vaccine passport is a digital or paper document that may serve as proof of the COVID-19 vaccine, thereby allowing entry to public venues, sporting events, air travel, and unrestricted access to other facilities. This study explores how the COVID-19 passport is being discussed and perceived on Twitter and the prominent entities involved in the early discourse on the issue. Twitter messages were theoretically analyzed for Health Belief Model (HBM) and Theory of Planned Behavior (TPB) variables, as well as message source, engagement, and attitudes towards vaccination certificates. Using quantitative content analysis, tweets were coded on nine dimensions: account type, tweeter profile, tweet content, tweet modality, attitude, self-efficacy, perceived barriers, benefits, and action cues. Most of the tweets originated from personal accounts, followed by media organizations, media-related personalities, politicians, and the travel industry. A significant number of tweets were from male Twitter users. Our analysis revealed that most tweeters had a favorable attitude towards the COVID-19 passports. Unfavorable attitudes toward the COVID-19 passport were based on reasons such as a lack of common standard or consensus, and personal freedoms & human rights. Tweets highlighting the benefits of COVID-19 passports cited travel as the primary reason. Based on a combination of technical, legal, and ethical practices, our study offers a set of vital recommendations for governments, health organizations, and businesses that may help stimulate the acceptance of vaccine passports.

Stability bounds of a delay visco-elastic rheological model with substrate friction.

Cells and tissues exhibit sustained oscillatory deformations during remodelling, migration or embryogenesis. Although it has been shown that these oscillations correlate with intracellular biochemical signalling, the role of these oscillations is as yet unclear, and whether they may trigger drastic cell reorganisation events or instabilities remains unknown. Here, we present a rheological model that incorporates elastic, viscous and frictional components, and that is able to generate oscillatory response through a delay adaptive process of the rest-length. We analyse its stability as a function of the model parameters and deduce analytical bounds of the stable domain. While increasing values of the delay and remodelling rate render the model unstable, we also show that increasing friction with the substrate destabilises the oscillatory response. This fact was unexpected and still needs to be verified experimentally. Furthermore, we numerically verify that the extension of the model with non-linear deformation measures is able to generate sustained oscillations converging towards a limit cycle. We interpret this sustained regime in terms of non-linear time varying stiffness parameters that alternate between stable and unstable regions of the linear model. We also note that this limit cycle is not present in the linear model. We study the phase diagram and the bifurcations of the non-linear model, based on our conclusions on the linear one. Such dynamic analysis of the delay visco-elastic model in the presence of friction is absent in the literature for both linear and non-linear rheologies. Our work also shows how increasing values of some parameters such as delay and friction decrease its stability, while other parameters such as stiffness stabilise the oscillatory response.

Cost estimation alongside a multi-regional, multi-country randomized trial of antenatal ultrasound in five low-and-middle-income countries.

BACKGROUND: Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency. METHODS: We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses. RESULTS: Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD). CONCLUSIONS: Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers). TRIAL REGISTRATION: Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).

Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.

BACKGROUND: Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. METHODS: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. RESULTS: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. CONCLUSIONS: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.

In vitro Assessment of Tris Egg Yolk and Soybean Lecithin Based Extenders for Cryopreservation of Crossbred Ram Semen.

BACKGROUND: The replacement of egg yolk with alternative plant-derived soybean lecithin is gaining interest in both animal and human sperm cryopreservation owing to biosecurity issues with egg yolk based extenders. OBJECTIVE: To evaluate the comparative effect of egg yolk and soyabean lecithin based extenders on the quality of cryopreserved crossbred ram semen. METHODS: Pooled ejaculates (total ejaculates = 36) were divided into two aliquots and extended with Tris egg yolk extender (Tris extender) and soybean lecithin based commercial extender (Ovixcell) RESULTS: Among the two extenders, Ovixcell showed better sperm quality both at the pre-freeze (Sperm motility) and post-thaw stages. Lower malondialdehyde (MDA) level (nmol/mL) was observed in Ovixcell as compared to Tris extender. Both sperm quality and MDA level decreased significantly (P < 0.05) from pre-freeze to post-thaw in both the extenders. CONCLUSION: The findings of the present study indicate that Ovixcell is a comparable alternative to Tris extender for the cryopreservation of crossbred ram semen.

Early initiation of direct anticoagulation after stroke in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: The safety of early initiation of anticoagulant therapy in patients with ischaemic stroke related to atrial fibrillation (AF) is unknown. We investigated the safety of early initiation of direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs) or no anticoagulation. METHODS: This observational, retrospective, single-centre study included consecutive patients with recent (<4 weeks) ischaemic stroke and AF. The primary outcome was the rate of major (intracranial and extracranial) bleeding in patients on different treatment schemes, i.e. DOACs, VKAs and not anticoagulated. We also investigated the rate of ischaemic cerebrovascular events and mortality. RESULTS: We included 959 consecutive patients with AF and ischaemic stroke followed up for an average of 16.1 days after the index event. A total of 559 out of 959 patients (58.3%) were anticoagulated with either VKAs (n = 259) or DOACs (n = 300). Anticoagulation was started after a mean of 7 ± 9.4 days in the DOAC group and 11.9 ± 19.7 days in the VKA group. Early initiation of any anticoagulant was not associated with an increased risk of any major bleeding [odds ratio (OR), 0.49; 95% confidence intervals (CI), 0.21-1.16] and in particular of intracranial bleeding (OR, 0.47; 95% CI, 0.17-1.29; P = 0.143) compared with no anticoagulation. In contrast to VKAs (OR, 0.78; 95% CI, 0.28-2.13), treatment with DOACs (OR, 0.32; 95% CI, 0.10-0.96) reduced the rate of major bleeding compared with no anticoagulation. Early recurrences of ischaemic stroke did not differ significantly among the three groups. CONCLUSIONS: Starting DOACs within a mean of 7 days after stroke appeared to be safe. Randomized controlled studies are needed to establish the added efficacy of starting anticoagulation early after stroke.

Anti-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody in necrotizing myopathy: treatment outcomes, cancer risk, and role of autoantibody level.

Objective: To evaluate clinical associations of anti-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody (Ab) and statin exposure in necrotizing myopathy (NM) patients. Methods: NM without a known myositis-specific autoantibody (MSA) was ascertained from a large single-centre myositis database between 1985 and 2012. A comparison NM cohort included 32 anti-SRP+ autoantibody patients, and other control groups included 74 non-NM myositis patients and 21 non-myositis controls. Sera from all cases and controls were tested using a validated anti-HMGCR enzyme-linked immunosorbent assay. Clinical features including statin use and anti-HMGCR Ab status were compared between cases and controls. Results: Of the 256 NM muscle biopsies reviewed, only 48 subjects with available sera were identified as traditional MSA-negative NM. Anti-HMGCR positivity was significantly (p < 0.001) associated with MSA-negative NM [48% (23/48)] compared to all of the myositis and non-myositis controls [5% (6/127)]. Most anti-HMGCR Ab-positive NM patients had high titres of anti-HMGCR (83%) and a history of statin exposure (78%), along with severe muscle weakness, high creatine kinase (CK) levels (90% ≥ 5000 IU/L), a paucity of other organ manifestations, and the need for immunosuppression with prednisone and methotrexate, but generally favourable outcomes. Anti-HMGCR serum levels were associated with baseline CK levels but not muscle weakness. Conclusion: HMGCR Ab-positive NM patients are associated with statin exposure, have severe muscle weakness and high CK at presentation, lack other organ manifestations, and generally have favourable outcomes from immunosuppression. Anti-HMGCR Abs should be assessed in MSA-negative NM patients, particularly those with a history of statin exposure.

The Impact of Elastic Deformations of the Extracellular Matrix on Cell Migration.

The mechanical properties of the extracellular matrix, in particular its stiffness, are known to impact cell migration. In this paper, we develop a mathematical model of a single cell migrating on an elastic matrix, which accounts for the deformation of the matrix induced by forces exerted by the cell, and investigate how the stiffness impacts the direction and speed of migration. We model a cell in 1D as a nucleus connected to a number of adhesion sites through elastic springs. The cell migrates by randomly updating the position of its adhesion sites. We start by investigating the case where the cell springs are constant, and then go on to assuming that they depend on the matrix stiffness, on matrices of both uniform stiffness as well as those with a stiffness gradient. We find that the assumption that cell springs depend on the substrate stiffness is necessary and sufficient for an efficient durotactic response. We compare simulations to recent experimental observations of human cancer cells exhibiting durotaxis, which show good qualitative agreement.