Protocol change improves live birth and recurrent cycle cancellation rates after a previous IVF cycle cancellation: an analysis of 13 000 autologous cycles reported to SART CORS.

STUDY QUESTION: After an IVF cycle cancellation, does changing the stimulation protocol affect the odds of live birth and recurrent cancellation in the subsequent cycle? SUMMARY ANSWER: After IVF cycle cancellation, compared to those who repeated the same stimulation protocol, those who changed their protocol had higher odds of live birth and lower odds of recurrent cycle cancellation. WHAT IS KNOWN ALREADY: There is limited data addressing the effect of changing the stimulation protocol after an IVF cycle is cancelled during initial stimulation. The odds of live birth outcomes are not known so far in studies addressing the effect of changing the protocol. STUDY DESIGN, SIZE, DURATION: Retrospective Cohort Study using the 2014-2017 Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database. PARTICIPANTS/MATERIALS, SETTING, METHODS: The data included 13 135 patients with a first autologous IVF cycle that resulted in a cycle cancellation and was followed by a second autologous cycle within the study period. We excluded fertility preservation cycles, supernumerary cycle attempts after the second IVF cycle attempt, and cycles with more than one stimulation protocol documented per cycle start. Patients who received the same protocol for both cycles (n = 6434) were compared to those who changed their protocol in the second cycle (n = 6701). Multivariable logistic regression analyses were performed to estimate the adjusted odds of live birth and recurrent cancellation. MAIN RESULTS AND THE ROLE OF CHANCE: Changing the protocol in the second cycle resulted 14% lower odds of recurrent cycle cancellation (P = 0.01) and 17% higher odds of live birth after fresh transfers (P = 0.04). When stratifying the data by specific combinations of protocol change (agonist flare, agonist suppression, antagonist), there was an increase in live birth when switching from antagonist to agonist suppression (odds ratio (OR) = 1.36, P = 0.03) and from agonist suppression to antagonist (OR = 1.73, P = 0.01) compared to those who repeated their same stimulation protocol. Specifically in poor responders, outcomes were worse when using the agonist flare protocol and significantly improved with the agonist suppression protocol. LIMITATIONS, REASONS FOR CAUTION: Comparison of response to stimulation between first and second cycles cannot be made in this study because the index IVF cycle was cancelled during ovarian stimulation, and thus there is no reportable outcome data for that cycle. Additionally, SART only tracks the three stimulation protocols addressed in this study and does not have data on more contemporary protocols that are used in poor responders thus limiting the generalizability of our findings. WIDER IMPLICATIONS OF THE FINDINGS: Using the SART CORS database, which includes >90% of all reported IVF cycles in the USA, provides generalizability to the demographically diverse IVF populations found here. In agreement with prior studies assessing change in IVF protocols, the agonist flare protocol seems to result in worse IVF outcomes, and based on our results, we believe that there is no role for the agonist flare protocol in patients with a prior poor response to stimulation. STUDY FUNDING/COMPETING INTEREST(S): None declared. TRIAL REGISTRATION NUMBER: N/A.

Serious Failure Modes After EVAR Are Device Specific.

OBJECTIVES: Type I and III endoleaks following endovascular aneurysm repair (EVAR) can lead to catastrophic events that require major re-interventions. We reviewed our experience with aortic endograft re-interventions for type I and III endoleaks and other serious failures among different devices. METHODS: We retrospectively reviewed patients with a prior EVAR who underwent open conversion (OC) or major endovascular intervention (MEI) (re-lining, cuff/limb extension, parallel graft) for type I/III endoleaks at our institution from 2002 to 2019. Baseline characteristics, procedural details, re-interventions, and outcomes were collected. RESULTS: A total of 229 patients (194 men) underwent re-interventions for type I and III endoleaks after EVAR (90 OC, 139 MEI) for devices implanted between 1997 and 2019. Average age at re-intervention was 78±8.5 years. A total of 135 (59%) were implanted at our institution, whereas 93 (41%) were referred. Median time to re-intervention was 4 years with 25% to 75% interquartile range (IQR) of 2.2-6.6 years. There was no significant difference in baseline demographics or type of re-interventions (OC/MEI) between device types. 42/229 (18%) presented with ruptured aneurysms, 20/229 (9%) were symptomatic, whereas the rest presented with asymptomatic radiographic findings. Type 1A endoleak was present in 146/229 (63.8%-72 with proximal migration), type IB in 46/229 (20.1%), type IIIA in 37/229 (16.6%), type IIIB in 15/229 (6.5%), and persistent aneurysm sac growth with no radiographic evidence of an endoleak in 6/229 (2.6%). Devices included most commercial products: AFX, Excluder, AneuRx, Ancure, Endurant, and Zenith. A smaller number of investigational devices accounted for the rest. Type 1A endoleak was the most common indication for re-intervention among all devices except for AFX and ancure devices, proximal migration was a frequent presentation with AneuRx. AFX devices more frequently presented with a type III and ancure devices more frequently presented with a type IB endoleak. CONCLUSIONS: Serious failure modes after EVAR differ between endografts and occur throughout the follow-up period. This is important to guide targeted interrogation of surveillance studies and follow-up schedules, even for discontinued devices, as well as comparisons between various series and estimation of EVAR failure rates. CLINICAL IMPACT: Surveillance after EVAR is critical for long term success of the repair, understanding of the differential modes of failure of every graft available is important in the longitudinal evaluation of these endografts. Equally important is the understanding of the modes of failure of legacy endografts that are no longer on the market but still being followed, in order to be able to tailor a surveillance regiemn and the evntual repair if needed.

Effect of prostaglandin alone and in combination with trace minerals on the follicular and luteal dynamics, estrus response and pregnancy in sub-estrus buffaloes (Bubalus bubalis).

Sub-estrus is a condition when buffaloes do not display behavioural estrus signs, despite being in estrus and causes a delay in conception and increases the service period. The present study describes the effect of synthetic prostaglandin (PGF2α) alone and in combination with trace minerals on the follicular and corpus luteum (CL) dynamics, serum estradiol (E2) and progesterone (P4) concentration correlating estrus response and pregnancy outcome in sub-estrus buffaloes during the breeding season. A total of 50 sub-estrus buffaloes, identified through ultrasonography (USG) examination, were randomly allocated into three groups, viz. T1 (Synthetic PGF2α, Inj. Cloprostenol 500 µg, i.m, n = 17), T2 (Synthetic PGF2α + Trace mineral supplementation, Inj. Stimvet 1 mL/100 kg body weight, i.m., n = 17) and control (untreated; n = 16). Following treatment, 100% of sub-estrus buffaloes were induced estrus in the T1 and T2 groups, while only 18.75% were induced in the control. The CL diameter and serum P4 concentration were significantly lower at post-treatment, whereas the pre-ovulatory follicle (POF) size and serum E2 concentration were significantly higher in the T1 and T2 groups as compared to the control (p < .05). The buffaloes of the T2 group had a greater proportion of moderate intensities estrus than those of T1. Moreover, the proportion of buffaloes conceived in the T1 and T2 were 41.2% and 52.95%, respectively. The larger POF diameter and higher serum E2 concentration were associated with intense intensity estrus and higher conception rate (66.7%) in sub-estrus buffaloes. Similarly, CL regression rate, POF size and serum E2 concentration were relatively higher in the buffaloes conceived as compared to those not conceived. It is concluded that synthetic PGF2α in combination with trace minerals induces moderate to intense intensities estrus in a greater proportion of sub-estrus buffaloes and increases the conception rate during the breeding season. Moreover, behavioural estrus attributes correlating follicle and luteal morphometry, serum E2 and P4 concentration could be used to optimise the breeding time for augmenting the conception rate in sub-estrus buffaloes.

Next-generation hybrid technologies for the treatment of pharmaceutical industry effluents.

Water and industries are intangible units of the globe that are always set to meet the population's demand. The global population depends on one-third of freshwater increasing the demand. The increase in population along with urbanization has polluted the fresh water resources. The pharmaceutical industry is marked as an emerging contaminant of water pollution. The most common type of pharmaceutical drugs that are detected in the environment includes antibiotics, analgesics, NSAIDs, and pain-relieving drugs. These drugs alter the food chain of the organisms causing chaos mainly in the marine ecosystem. Pharmaceutical drugs are found only in shallow amounts (ng/mg) they have a huge impact on the living system. The consumption of water contaminated with pharmaceutical ingredients can disrupt reproduction, hormonal imbalance, cancer, and respiratory problems. Various methods are used to remove these chemicals from the environment. In this review, we mainly focused on the emerging hybrid technologies and their significance in the effective treatment of pharmaceutical wastewater. This review paper primarily elaborates on the merits and demerits of existing conventional technologies helpful in developing integrated technologies for the modern era of pharmaceutical effluent treatment. This review paper further in detail discusses the various strategies of eco-friendly bioremediation techniques namely biostimulation, bioaugmentation, bacterial degradation, mycoremediation, phytoremediation, and others for the ultimate removal of pharmaceutical contaminants in wastewater. The review makes clear that targeted and hybrid solutions are what the world will require in the future to get rid of these pharmacological prints.

Computational-sampling-moiré-based on-machine alignment for freeform optics.

The manufacturing and characterization of freeform optical surfaces are influenced by their high sensitivity to misalignments. In this work, the computational sampling moiré technique combined with phase extraction is developed for the precise alignment of freeform optics during fabrication and in metrology applications. This novel, to the best of our knowledge, technique achieves near-interferometry-level precision in a simple and compact configuration. This robust technology can be applied to industrial manufacturing platforms (such as diamond turning machines, lithography, and other micro-nano-machining techniques) as well as their metrology equipment. In a demonstration of computational data processing and precision alignment using this method, iterative manufacturing of freeform optical surfaces with a final-form accuracy of about 180 nm was accomplished.

Response assessment by positron emission tomography-computed tomography as compared with contrast-enhanced computed tomography in childhood Hodgkin lymphoma can reduce the need for radiotherapy in low- and middle-income countries.

INTRODUCTION: The InPOG-HL-15-01, a multicentric prospective study, used a risk-stratified and response-based approach with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) backbone to treat children and adolescents with newly diagnosed Hodgkin lymphoma (HL) and reduce the use of radiation therapy (RT). Children/adolescents with bulky disease or inadequate response at early response assessment (ERA) after two cycles of chemotherapy were assigned to receive RT. For ERA, positron emission tomography computed tomography (PET-CT) was recommended but not mandatory in view of limited access. This study aimed to compare the impact of using contrast-enhanced computed tomography (CECT) and PET-CT on treatment decisions and outcomes. METHODOLOGY: 396 patients were enrolled and 382 had an ERA at the assigned time point. Satisfactory response was defined as Deauville score 3 or less for patients undergoing PET-CT and complete response (CR)/very good partial response (VGPR) for patients undergoing CECT. Outcomes of interest incorporate 5 year event-free survival (EFS), EFS including abandonment (EFSa), and overall survival (OS). RESULTS: At ERA, satisfactory response was documented in 277 out of 382 (72.5%) participants and this was significantly higher in PET-CT (151 out of 186, 81.2%) as compared with CECT-based assessments (126 out of 196, 64.3%) respectively (p value < .001). Amongst the 203 patients with nonbulky disease (wherein the indication for RT was entirely dependent on ERA), 96 out of 114 (84.2%) and 61 out of 89 (68.5%) patients achieved a satisfactory response according to the PET-CT and CECT (p value = .008) respectively and hence a lesser proportion of patients in the PET-CT arm received RT. Despite a lower usage of RT the 5 year OS of both groups, ERA based on CECT (91.8%) versus PET-CT (94.1%) was comparable (p value = .391) and so was the 5 year EFS (86.7 vs. 85.5%, p value = .724). CONCLUSION: Use of PET-CT as the modality for ERA is more likely to indicate a satisfactory response as compared with CECT and thereby decreases the need for RT in response-based treatment algorithm for HL-afflicted children. The reduction in the application of RT did not impact the overall outcome and plausibly would lower the risk of delayed toxic effects.

Heat ameliorative measures in Murrah buffalo (Bubalus bubalis) heifers during summer: effect on microclimate, thermal comfort, and behavior.

Water buffalo (Bubalus bubalis) is the mainstay of milk production in Asian countries including India. However, the hot climate of the country remains the biggest bottleneck to exploit the potential of this species. Therefore, a study was conducted to assess the effect of heat ameliorative measures on microclimate, thermal comfort, and behavior of Murrah buffalo heifers during summer. Buffalo heifers (n = 24) between the age of 15 and 20 months with a mean body weight of 363.75 ± 11.27 kg were randomly grouped into four treatments based on their age and body weight. The heifers kept in the shed without any cooling served as CON (control), while the animals of group CJ were tied with a cooling jacket. The buffalo heifers of the CJF group were subjected to the cooling jacket with forced air ventilation, whereas the intermittent (10 min at 2-h intervals) sprinkling followed by forced air ventilation was practiced in group SF between 900 and 1800 h throughout the experiment. The microclimatic variables were low in the sheds of groups CJ, CJF, and SF than the CON. The physiological responses such as rectal temperature, skin temperature, respiration rate, and pulse rate were reduced in groups CJ, CJF, and SF than the CON at 1400 h. The serum cortisol was less in the CJF and SF than those of CON group. The animals of the CJ, CJF, and SF groups spent more time for feeding and rumination with less frequent longer bouts. The extended periods of lying followed by shorter standing and idling were observed in groups CJ, CJF, and SF when compared with the CON. It may be therefore concluded that cooling jacket and intermittent sprinkling in combination with forced air ventilation might be helpful in improving the micro-environment, thermal comfort, and behavior of buffalo heifers particularly under tropical climates during summer.

High prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies among unvaccinated children of Chandigarh, Northwest India, in a household-based paediatric serosurvey post-second wave of pandemic (June to July 2021).

OBJECTIVE: Current national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination policy covers children aged >12 years. Unvaccinated, uninfected children remain susceptible to SARS-CoV-2 and play a role in community transmission, as paediatric infection is mostly mild or asymptomatic. To estimate the proportion of susceptible children in a community for public health measures, there is a need to assess the extent of natural infection. STUDY DESIGN: We performed a cross-sectional household serosurvey of SARS-CoV-2 antibodies in unvaccinated children aged between 6 and 18 years after the second COVID-19 wave. METHODS: Anti-SARS-CoV-2 immunoglobin G (IgG) testing in serum was done using chemiluminescence immunoassay. We used a logistic regression model to investigate predicted factors of seropositivity. RESULTS: We observed a high prevalence (weighted average: 68.3%) of anti-SARS-CoV-2 IgG in 2700 enrolled children. Logistic regression for predictors of IgG seropositivity showed lower odds in households with completely vaccinated adults (adjusted odds ratio [OR]: 0.43, 95% confidence interval [CI]: 0.26-0.71, P = 0.0011) compared with households with unvaccinated adults. Other factors for low seropositivity included frontline workers as family members (adjusted OR: 0.69, 95% CI: 0.52-0.91, P = 0.0091) and non-crowded households (adjusted OR: 0.74, 95% CI: 0.61-0.89, P = 0.0019). CONCLUSION: A high SARS-CoV-2 IgG prevalence in unvaccinated children was indicative of previous exposure to potentially infected contacts. This implies in-person academic activities for children can be continued during future community transmission. Comparatively lower seropositivity in children of completely vaccinated households or frontline workers suggests decreased transmission due to vaccination-induced immunity of family members. Vaccination will still be required in these children to maintain protective IgG levels, particularly in low seroprevalence groups.

IGF-1 stabilizes goat sperm mitochondrial transmembrane potential and reduces dna fragmentation.

BACKGROUND: Antioxidant present in sperm cells protects them from oxidative damage. However, sperm are more susceptible to peroxidative damages due to the loss of these enzymes during cryopreservation and their survival and fertility may be compromised. Insulin like growth factor-1 (IGF-1) has an antioxidant effect and could maintain sperm motility. OBJECTIVE: To improve seminal parameters, mitochondrial membrane potential (MMP), oxidative status and DNA integrity of buck semen after freeze-thawing by fortification of goat semen diluent with various concentrations of IGF-1. MATERIALS AND METHODS: Fifty ejaculates were collected and were extended with tris- citric acid- fructose diluent with 10% egg yolk and 6% glycerol with sperm concentrations of 1×108 mL-1. Post-cryopreserved sperm were assessed for motility and a range of other functional parameters. RESULTS: In post-thaw semen sperm motility, live sperm count, acrosome integrity, hypo-osmotic swelling positive spermatozoa, malondialdehyde (MDA), protein carbonyl content (PCC), TUNEL positive sperm differed significantly (P<0.05) with the various concentrations of IGF-1 used. Sperm functional parameters post-thawing were significantly (P<0.05) better in 250 ng/mL IGF-1. IGF-1 protects against lipid peroxidation by lowering MDA and PCC production, thus reducing the harmful effect of reactive oxygen species. The kidding percentage using the artificial insemination technique was significantly higher ( i.e., 40%) in the group supplemented with 250 ng/mL of IGF-1 than in the non-supplemented group (i.e., 30%). CONCLUSION: IGF-1 may be used to improve post-thaw semen quality and fertility as measured by actual kidding rate. Doi.org/10.54680/fr23610110312.

Post-mortem computed tomography differentiation of putrefactive gas and air embolism: A case of traumatic carotid-jugular arteriovenous fistula.

INTRODUCTION: PMCT is superior to autopsy for identification of intravascular or extravascular gas pockets and their distribution. However, differentiation between air embolism and putrefactive gas can prove challenging due to overlapping imaging findings. CASE REPORT: We report a case of a healthy young man who was involved in a fight, sustained a slash wound to the right side of his head by a kitchen knife and died at the scene. Pre-autopsy PMCT demonstrated complex fractures of the right mastoid bone extending to the right petrous apex and jugular bulb, exposing the right sigmoid sinus. There was also asymmetric intravascular air distribution suspicious of air embolism with ancillary findings of traumatic carotid-jugular pseudoaneurysm and arteriovenous fistulous formation. Post-mortem examination revealed a slash wound measuring 12x2 cm at the right side of the head, cutting through the scalp, right temporal bone, right temporal meninges, right sigmoid venous sinus and part of the right occipital lobe. No intracranial haemorrhage was found on both PMCT and autopsy. DISCUSSION: PMCT findings of air embolism versus putrefactive air on PMCT are discussed in this case. Detailed history on mechanism, circumstances, time of death and careful analysis of intravascular and extravascular air distribution patterns on PMCT are essential in guiding differentiation of true fatal air embolism and "normal" post-mortem putrefactive air. Needless to say, it is recommended that PMCT be performed as early as possible after death to reduce the chances and presence of artifactual decomposition changes.

Optimal Detection of Latent Mycobacterium tuberculosis Infection by Combined Heparin-Binding Hemagglutinin (HBHA) and Early Secreted Antigenic Target 6 (ESAT-6) Whole-Blood Interferon Gamma Release Assays.

Optimal detection of latent tuberculosis (TB) infection (LTBI) remains a challenge, although it is essential to reach the goal of TB elimination. Our objective was to develop and clinically evaluate a user-friendly, 24-h, whole-blood (WB) interferon gamma (IFN-γ) release assay (IGRA) improving the detection of LTBI, compared to available tests. One milliliter of blood was divided into four aliquots and in vitro stimulated for 24 h with two different stage-specific mycobacterial antigens, i.e., heparin-binding hemagglutinin (HBHA) and early secreted antigenic target 6 (ESAT-6), a latency-associated antigen and a bacterial replication-related antigen, respectively, in addition to positive and negative controls. Clinical evaluation was performed on two independent cohorts of carefully selected subjects, i.e., a training cohort of 83 individuals and a validation cohort of 69 individuals. Both cohorts comprised LTBI subjects (asymptomatic people with a positive tuberculin skin test result and potential exposure to TB index cases), patients with active TB (aTB), and noninfected controls. The sensitivity and specificity of the WB-HBHA-IGRA to identify LTBI subjects among asymptomatic individuals were 93%. Combining the results in response to HBHA and ESAT-6 allowed us to identify LTBI subgroups. One group, with IFN-γ responses to HBHA only, was easily differentiated from patients with aTB. The other group, responding to both antigens like the aTB group, is likely at risk to reactivate the infection and should be prioritized for prophylactic anti-TB treatment. The combined WB-IGRA may be offered to clinicians for the selection of LTBI subjects to benefit from prophylactic treatment.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

Molecular marker-based characterization of cytoplasm and restorer of male sterility (Ms) locus in commercially grown onions in India.

BACKGROUND: The cytoplasmic-genic male-sterility system has been extensively employed for the production of onion hybrids. Molecular marker-assisted characterization of the cytotypes and genotyping at the restorer-of male-fertility (Ms) locus is important for the accelerated breeding of onion hybrids. Indian onion breeding has focussed more on open-pollinated varieties than hybrids. To accelerate the breeding efforts, marker-assisted selection (MAS) plays a pivotal role. METHODS AND RESULTS: This study aimed to characterize the Indian breeding lines, varieties, hybrids, and exotic accessions for cytotype and Ms locus. For cytoplasm, cytotype markers, accD, and MKFR and for Ms locus identification, PCR markers AcPMS1 and AcSKP1 were employed. Bulk strategy to identify cytoplasm and Ms locus was tested. Sequencing of PCR products amplified by accD was also tried. Both the accD and MKFR were synonymous in cytoplasm identification except in T821 where T cytoplasm was identified. AcPMS1 was more reliable than AcSKP1 for Ms locus identification. Sequencing proved that N and T cytoplasm are identical. Bulking strategy can be used for cytotype identification but not for Ms locus. CONCLUSIONS: Indian onions have a predominance of normal (N) cytoplasm and homozygous recessive (msms) locus. This might be beneficial for hybrid development. S cytoplasm was identified in exotic varieties. For the first time, T cytoplasm has been reported from India. These findings will assist Indian onion breeders to develop MAS strategies for accelerating hybrid development programs. And for the release of onion hybrids with high productivity and uniformity.

STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in a validation dataset derived from the screened population of the STATIN study. METHODS: This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. RESULTS: The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. CONCLUSION: The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Genetic and population diversity of Toxocara cati (Schrank, 1788) Brumpt, 1927, on the basis of the internal transcribed spacer (ITS) region.

The present investigation was aimed to study the sequence, phylogenetic and haplotype analyses of Toxocara cati based on the ITS region, along with the genetic diversity, demographic history and population-genetic structure. The maximum likelihood tree based on Kimura 2-parameter model was constructed using the complete ITS region of all the nucleotide sequences (n = 57) of Toxocara spp. and other related ascarid worms available in the GenBank™. It placed all the sequences of T. cati into four major clades designated as T. cati genotypes 1-4 (TcG1-G4). A total of 66 signature nucleotides were identified in the ITS region between genotypes. The median-joining haplotype network displayed a total of 24 haplotypes, with China exhibiting the highest number of haplotypes (h = 20) followed by India (h = 4), and Japan and Russia (h = 1). It indicated a clear distinction between all the four genotypes. The pairwise FST values between all the genotypes indicated huge genetic differentiation (> 0.25) between different T. cati genotypes. Moreover, the gene flow (Nm) between T. cati genotypes was very low. Results of AMOVA revealed higher genetic variation between genotypes (92.82%) as compared to the variation within genotypes (7.18%). The neutrality indices and mismatch distributions for the G1-G4 genotypes, Indian isolates and the overall dataset of T. cati indicated either a constant population size or a slight population increase. The geographical distribution of all the genotypes of T. cati is also reported. This is the first report of genotyping of T. cati on the basis of the ITS region.

Microclimate modification in Murrah buffalo (Bubalus bubalis) heifers during summer: Effect on intake, growth and hematobiochemistry.

The present investigation evaluated the effect of microclimate modification on feed intake, growth performance, and hemato-biochemical profile of Murrah buffalo (Bubalus bubalis) heifers during summer. Twenty-four buffalo heifers, between 15 and 20 months of age with an average body weight of 363.75 ± 11.27 kg, were randomly assigned to 4 groups based on their age and body weight. The heifers of the T0 (control) group were kept under the shed without any cooling treatment, while the animals in group T1 were tied with a cooling jacket. Buffalo heifers of group T2 were subjected to a cooling jacket with forced ventilation and animals in group T3 were treated with intermittent sprinkling (10 min., at 2 h intervals) and forced ventilation between 9.00 AM and 6.00 PM during the experiment. The ambient temperature inside the shed and core body temperature were reduced in groups T1, T2, and T3 compared to T0. Heifers had higher dry matter intake when subjected to cooling treatments T1, T2, and T3, whereas water intake was reduced in T2 and T3 groups. The animals in T2 and T3 groups attained higher average daily weight gain, while the feed conversion was better in the T3 group compared to T0. The hematological measures such as hemoglobin, total erythrocyte count, and total leucocyte count were found higher in T0. The serum glucose, sodium, and potassium levels increasedand alkaline phosphatase activity decreased in groups T1, T2 and T3 when compared with T0. It can be concluded that the provision of intermittent sprinkling and cooling jacket in combination with forced ventilation could improve the microclimate, which in turn could enhance the performance of Murrah heifers during hot summer days in the tropics.

The opinion of general practitioners in Malaysia on newly imposed third party health administrator policies in primary care.

BACKGROUND: Third Party Health Administrators (TPA) has become an integral part in the field of funding healthcare for most parts in the world. Although they ensure access to medical care when out-of-pocket payment is required, TPAs have been found to impose unreasonable dictation in medicine prescriptions that undercuts doctors remuneration including paying very low medical consultation fees, types/methods of treatment and modalities for their policy holders. The objective of this study was to get the opinion of Malaysian doctors regarding the newly imposed policies and rates that these companies have forcibly dictated towards private primary care General Practitioners (GPs). MATERIALS AND METHODS: This was a cross sectional study, conveniently sampling private GPs currently practicing in Malaysia. A self-developed online questionnaire was sent out to the members via social media with the assistance of the Malaysian Medical Association the affiliates of Federation of Private Medical Practitioners Associations of Malaysia and Medical Practitioners Coalition Association of Malaysia. Data was collected from April to July 2021. A series of 7 short questions were asked in the survey to yield a higher response rate. A population to proportion sample size was calculated and a minimum of 365 responses were required. All data collected were collated and analysed in the SPSS v21.0 RESULTS: From a total of 7,000 GPs, 491 GPs (134.52% of intended sample size) responded to the questionnaire. The largest portion of respondents were from Selangor (21.79%). A total of 65.58% of the GPs felt that the RM 15 consultation fee dictated by the TPAs was unfair, 71.08% felt it was unfair that TPA overwrote certain investigations done or medicines given as over-treatment, 90.84% felt that TPAs had no jurisdiction to dictate the number of days of medication patients needed for chronic medical conditions, 95.52% did not agree that TPAs fix the price of each medication, 54.58% agreed that marking up medications from 5-15% of the original purchase price was fair and 68.64% agreed that they would boycott TPAs that were unreasonable with their dictation/demands. CONCLUSION: GPs generally disagreed with many new policies imposed by TPAs. These new policies might hinder the screening, management and early detection of chronic non communicable diseases here in Malaysia.

Introducing Clinical Pathology Course to Fourth Year Medical Students as a Bridge between Pre-clinical and Clinical Medical Sciences.

There isn't any vertical integration of pre-clinical and clinical sciences subjects in the existing Kathmandu University MBBS curriculum. Many of the graduates are not able to correlate the clinico-pathological aspects of various diseases as a result the rational use of investigations for diagnosing various diseases is compromised. There are few published examples of implementation of pathology instruction courses during the clinical years of medical training but it is not universally practiced. This lack of exposure to pathology may lead to poor understanding of laboratory testing and the role of pathologists in patient care. To set and implement an exemplary vertical integration of pre-clinical science with clinical science. A 12 credit hours clinical pathology education course comprising clinical hematology, cytopathology and histopathology was developed. Students belonging from the ongoing fourth year MBBS course of Birat Medical College were enrolled in the course. All of the interactive lecture sessions were delivered via an e-learning interface, using the Zoom platform as the main teaching methods. Evaluation of students' achievement of learning objectives was conducted through distributing pre and post-test online multiple-choice questionnaires. Chi-square tests were used to compare the variables between pre-test and post-test questionnaire responses. Results suggested that the designed clinical pathology course is valuable. The pretest and post-test questionnaire responses revealed the positive impact regarding the importance of introducing clinical pathology courses within the clinical year of MBBS undergraduate curriculum. Response rate to the online session was 100%. The point of agreement between the pre-test and post-test questionnaire responses were highly achieved after intervention of the clinical pathology course. A statistically significant result (p < 0.05) between all of the pre-test and post-test questionnaire responses was noted. There was a strong positive recommendation for incorporating clinical laboratory medicine courses within the MBBS clinical science curriculum. The improvement observed among fourth-year MBBS students on learning the importance of clinical pathology courses was encouraging. This experience thus contributed to set and implement an exemplary vertical integration of pre-clinical science with clinical science.

Krüppel-like factor 1 (KLF1) gene single nucleotide polymorphisms in sickle cell disease and its association with disease-related morbidities.

Sickle cell disease has varied clinical symptoms, and patients having high fetal hemoglobin (HbF) have milder symptoms. Various genetic factors are known to modulate the HbF levels. Krüppel-like factor 1 (KLF1) is a transcription factor that regulates the beta-like globin gene expression. Any variation in KLF1 gene may alter the sickle cell disease phenotype. Xmn-I polymorphism is also known to regulate the gamma globin gene expression. Present studies were carried out to investigate the effect of KLF1 gene mutations and Xmn-I polymorphism on the sickle cell disease severity and to ascertain the genotype-phenotype correlation. One hundred and eighteen sickle cell disease patients having a median follow-up of 5 years (3-10 years) were recruited. Clinical details were recorded from their retrospective medical records. Xmn-I polymorphism were analyzed using PCR-RFLP method. Variations in KLF1 gene were identified using Sanger sequencing. Out of 118 patients, 24 had acute chest syndrome and 21 patients had more than 2 pain episodes per year. There were no significant differences in sickle cell disease-related morbidities in male and females barring leg ulcers. A total of 6 polymorphism were observed in KLF1 gene, out of which 3 are novel (c.-304G > C, c.*141A > G and c.*178A > G). No statistically significant association of any of SNPs identified in KLF1 gene or Xmn-I polymorphism was seen with HbF levels as well as the sickle cell disease-related morbidities. No association exists between fetal hemoglobin or sickle cell disease-related morbidities and Xmn-I polymorphism or with SNPs identified in KLF1 gene in the studied cohort.