Rabies control in Bangladesh and prediction of human rabies cases by 2030: a One Health approach.

Background: Bangladesh is making progress toward achieving zero dog-mediated rabies deaths by 2030, a global goal set in 2015. Methods: Drawing from multiple datasets, including patient immunisation record books and mass dog vaccination (MDV) databases, we conducted a comprehensive analysis between 2011 and 2023 to understand the effectiveness of rabies control programmes and predict human rabies cases in Bangladesh by 2030 using time-series forecasting models. We also compared rabies virus sequences from GenBank in Bangladesh and other South Asian countries. Findings: The estimated dog population in Bangladesh was determined to be 1,668,140, with an average dog population density of 12.83 dogs/km2 (95% CI 11.14-14.53) and a human-to-dog ratio of 86.70 (95% CI 76.60-96.80). The MDV campaign has led to the vaccination of an average of 21,295 dogs (95% CI 18,654-23,935) per district annually out of an estimated 26,065 dogs (95% CI 22,898-29,230). A declining trend in predicted and observed human rabies cases has been identified, suggesting that Bangladesh is poised to make substantial progress towards achieving the 'Zero by 30' goal, provided the current trajectory continues. The phylogenetic analysis shows that rabies viruses in Bangladesh belong to the Arctic-like-1 group, which differs from those in Bhutan despite sharing a common ancestor. Interpretation: Bangladesh's One Health approach demonstrated that an increase in MDV and anti-rabies vaccine (ARV) resulted in a decline in the relative risk of human rabies cases, indicating that eliminating dog-mediated human rabies could be achievable. Funding: The study was supported by the Communicable Disease Control (CDC) Division of the Directorate General of Health Services (DGHS) of the People's Republic of Bangladesh.

Geographic disparities and temporal changes of diabetes-related mortality risks in Florida: a retrospective study.

Background: Over the last few decades, diabetes-related mortality risks (DRMR) have increased in Florida. Although there is evidence of geographic disparities in pre-diabetes and diabetes prevalence, little is known about disparities of DRMR in Florida. Understanding these disparities is important for guiding control programs and allocating health resources to communities most at need. Therefore, the objective of this study was to investigate geographic disparities and temporal changes of DRMR in Florida. Methods: Retrospective mortality data for deaths that occurred from 2010 to 2019 were obtained from the Florida Department of Health. Tenth International Classification of Disease codes E10-E14 were used to identify diabetes-related deaths. County-level mortality risks were computed and presented as number of deaths per 100,000 persons. Spatial Empirical Bayesian (SEB) smoothing was performed to adjust for spatial autocorrelation and the small number problem. High-risk spatial clusters of DRMR were identified using Tango's flexible spatial scan statistics. Geographic distribution and high-risk mortality clusters were displayed using ArcGIS, whereas seasonal patterns were visually represented in Excel. Results: A total of 54,684 deaths were reported during the study period. There was an increasing temporal trend as well as seasonal patterns in diabetes mortality risks with high risks occurring during the winter. The highest mortality risk (8.1 per 100,000 persons) was recorded during the winter of 2018, while the lowest (6.1 per 100,000 persons) was in the fall of 2010. County-level SEB smoothed mortality risks varied by geographic location, ranging from 12.6 to 81.1 deaths per 100,000 persons. Counties in the northern and central parts of the state tended to have high mortality risks, whereas southern counties consistently showed low mortality risks. Similar to the geographic distribution of DRMR, significant high-risk spatial clusters were also identified in the central and northern parts of Florida. Conclusion: Geographic disparities of DRMR exist in Florida, with high-risk spatial clusters being observed in rural central and northern areas of the state. There is also evidence of both increasing temporal trends and Winter peaks of DRMR. These findings are helpful for guiding allocation of resources to control the disease, reduce disparities, and improve population health.

Harnessing biotechnology for penicillin production: Opportunities and environmental considerations.

Since the discovery of antibiotics, penicillin has remained the top choice in clinical medicine. With continuous advancements in biotechnology, penicillin production has become cost-effective and efficient. Genetic engineering techniques have been employed to enhance biosynthetic pathways, leading to the production of new penicillin derivatives with improved properties and increased efficacy against antibiotic-resistant pathogens. Advances in bioreactor design, media formulation, and process optimization have contributed to higher yields, reduced production costs, and increased penicillin accessibility. While biotechnological advances have clearly benefited the global production of this life-saving drug, they have also created challenges in terms of waste management. Production fermentation broths from industries contain residual antibiotics, by-products, and other contaminants that pose direct environmental threats, while increased global consumption intensifies the risk of antimicrobial resistance in both the environment and living organisms. The current geographical and spatial distribution of antibiotic and penicillin consumption dramatically reveals a worldwide threat. These challenges are being addressed through the development of novel waste management techniques. Efforts are aimed at both upstream and downstream processing of antibiotic and penicillin production to minimize costs and improve yield efficiency while lowering the overall environmental impact. Yield optimization using artificial intelligence (AI), along with biological and chemical treatment of waste, is also being explored to reduce adverse impacts. The implementation of strict regulatory frameworks and guidelines is also essential to ensure proper management and disposal of penicillin production waste. This review is novel because it explores the key remaining challenges in antibiotic development, the scope of machine learning tools such as Quantitative Structure-Activity Relationship (QSAR) in modern biotechnology-driven production, improved waste management for antibiotics, discovering alternative path to reducing antibiotic use in agriculture through alternative meat production, addressing current practices, and offering effective recommendations.

Geographic disparities and predictors of COVID-19 vaccination in Missouri: a retrospective ecological study.

Background: Limited information is available on geographic disparities of COVID-19 vaccination in Missouri and yet this information is essential for guiding efforts to improve vaccination coverage. Therefore, the objectives of this study were to (a) investigate geographic disparities in the proportion of the population vaccinated against COVID-19 in Missouri and (b) identify socioeconomic and demographic predictors of the identified disparities. Methods: The COVID-19 vaccination data for time period January 1 to December 31, 2021 were obtained from the Missouri Department of Health. County-level data on socioeconomic and demographic factors were downloaded from the 2020 American Community Survey. Proportions of county population vaccinated against COVID-19 were computed and displayed on choropleth maps. Global ordinary least square regression model and local geographically weighted regression model were used to identify predictors of proportions of COVID-19 vaccinated population. Results: Counties located in eastern Missouri tended to have high proportions of COVID-19 vaccinated population while low proportions were observed in the southernmost part of the state. Counties with low proportions of population vaccinated against COVID-19 tended to have high percentages of Hispanic/Latino population (p = 0.046), individuals living below the poverty level (p = 0.049), and uninsured (p = 0.015) populations. The strength of association between proportion of COVID-19 vaccinated population and percentage of Hispanic/Latino population varied by geographic location. Conclusion: The study findings confirm geographic disparities of proportions of COVID-19 vaccinated population in Missouri. Study findings are useful for guiding programs geared at improving vaccination coverage and uptake by targeting resources to areas with low proportions of vaccinated individuals.

Geographic disparities and temporal changes of COVID-19 hospitalization risks in North Dakota.

Background: Although the burden of the coronavirus disease 2019 (COVID-19) has been different across communities in the US, little is known about the disparities in COVID-19 burden in North Dakota (ND) and yet this information is important for guiding planning and provision of health services. Therefore, the objective of this study was to identify geographic disparities of COVID-19 hospitalization risks in ND. Methods: Data on COVID-19 hospitalizations from March 2020 to September 2021 were obtained from the ND Department of Health. Monthly hospitalization risks were computed and temporal changes in hospitalization risks were assessed graphically. County-level age-adjusted and spatial empirical Bayes (SEB) smoothed hospitalization risks were computed. Geographic distributions of both unsmoothed and smoothed hospitalization risks were visualized using choropleth maps. Clusters of counties with high hospitalization risks were identified using Kulldorff's circular and Tango's flexible spatial scan statistics and displayed on maps. Results: There was a total of 4,938 COVID-19 hospitalizations during the study period. Overall, hospitalization risks were relatively stable from January to July and spiked in the fall. The highest COVID-19 hospitalization risk was observed in November 2020 (153 hospitalizations per 100,000 persons) while the lowest was in March 2020 (4 hospitalizations per 100,000 persons). Counties in the western and central parts of the state tended to have consistently high age-adjusted hospitalization risks, while low age-adjusted hospitalization risks were observed in the east. Significant high hospitalization risk clusters were identified in the north-west and south-central parts of the state. Conclusions: The findings confirm that geographic disparities in COVID-19 hospitalization risks exist in ND. Specific attention is required to address counties with high hospitalization risks, especially those located in the north-west and south-central parts of ND. Future studies will investigate determinants of the identified disparities in hospitalization risks.

Geographic disparities and temporal changes of COVID-19 incidence risks in North Dakota, United States.

BACKGROUND: COVID-19 is an important public health concern due to its high morbidity, mortality and socioeconomic impact. Its burden varies by geographic location affecting some communities more than others. Identifying these disparities is important for guiding health planning and service provision. Therefore, this study investigated geographical disparities and temporal changes of the percentage of positive COVID-19 tests and COVID-19 incidence risk in North Dakota. METHODS: COVID-19 retrospective data on total number of tests and confirmed cases reported in North Dakota from March 2020 to September 2021 were obtained from the North Dakota COVID-19 Dashboard and Department of Health, respectively. Monthly incidence risks of the disease were calculated and reported as number of cases per 100,000 persons. To adjust for geographic autocorrelation and the small number problem, Spatial Empirical Bayesian (SEB) smoothing was performed using queen spatial weights. Identification of high-risk geographic clusters of percentages of positive tests and COVID-19 incidence risks were accomplished using Tango's flexible spatial scan statistic. ArcGIS was used to display and visiualize the geographic distribution of percentages of positive tests, COVID-19 incidence risks, and high-risk clusters. RESULTS: County-level percentages of positive tests and SEB incidence risks varied by geographic location ranging from 0.11% to 13.67% and 122 to 16,443 cases per 100,000 persons, respectively. Clusters of high percentages of positive tests were consistently detected in the western part of the state. High incidence risks were identified in the central and south-western parts of the state, where significant high-risk spatial clusters were reported. Additionally, two peaks (August 2020-December 2020 and August 2021-September 2021) and two non-peak periods of COVID-19 incidence risk (March 2020-July 2020 and January 2021-July 2021) were observed. CONCLUSION: Geographic disparities in COVID incidence risks exist in North Dakota with high-risk clusters being identified in the rural central and southwest parts of the state. These findings are useful for guiding intervention strategies by identifying high risk communities so that resources for disease control can be better allocated to communities in need based on empirical evidence. Future studies will investigate predictors of the identified disparities so as to guide planning, disease control and health policy.

Sero-prevalence and risk factors associated with brucellosis in dairy cattle of Sylhet District, Bangladesh: A cross-sectional study.

BACKGROUND: Brucellosis is an emerging disease that causes a significant impact on productive and reproductive performance in dairy cattle. Though Brucella is a pivotal microorganism for dairy cattle, the scenario of brucellosis in Sylhet District is unknown. OBJECTIVES: A cross-sectional study was carried out to assess the prevalence and determinants associated with brucellosis in dairy cattle of Sylhet District. METHODS: A total of 386 sera and data on determinants from 63 dairy herds were collected from 12 sub-districts using simple random sampling. The sera were tested with Rose Bengal Brucella antigen test, Brucella abortus plate agglutination test and serum agglutination test to find out the sero-positivity. RESULTS: Overall, 17.09% (95% CI: 13.67-21.18) prevalence in cows were calculated. Relatively higher prevalence (56.08%; 95% CI: 42.23-70.32) was recorded in cows having parity ≥4 and were at higher risk (OR = 7.28) than the other cows with parity 0-3. Prevalence was significantly higher in cows with history of abortion 90.63% (95% CI: 75.79-96.76), repeat breeding 79.17% (95% CI: 65.74-88.27) and reproductive abnormalities 48.54% (95% CI: 39.12-58.07). Farm-level prevalence was high in farms with the previous history of abortion 95.45% (95% CI: 78.20-99.19) and repeat breeding 90.00% (95% CI: 74.38-96.54). CONCLUSIONS: The prevalence was high in Sylhet district, which might be a public health concern. Therefore, this study would represent the baseline information for guiding brucellosis control and prevention.

Isolation and characterization of mammalian orthoreovirus from bats in the United States.

Mammalian orthoreovirus (MRV) infects many mammalian species including humans, bats, and domestic animals. To determine the prevalence of MRV in bats in the United States, we screened more than 900 bats of different species collected during 2015-2019 by a real-time reverse-transcription polymerase chain reaction assay; 4.4% bats tested MRV-positive and 13 MRVs were isolated. Sequence and phylogenetic analysis revealed that these isolates belonged to four different strains/genotypes of viruses in Serotypes 1 or 2, which contain genes similar to those of MRVs detected in humans, bats, bovine, and deer. Further characterization showed that these four MRV strains replicated efficiently on human, canine, monkey, ferret, and swine cell lines. The 40/Bat/USA/2018 strain belonging to the Serotype 1 demonstrated the ability to infect and transmit in pigs without prior adaptation. Taken together, this is evidence for different genotypes and serotypes of MRVs circulating in US bats, which can be a mixing vessel of MRVs that may spread to other species, including humans, resulting in cross-species infections.

Prevalence of Eimeria spp. with associated risk factors in dairy calves in Sylhet, Bangladesh.

BACKGROUND: Bovine eimeriosis is thought to be very important for the productivity and health of cattle all over the world. Despite the importance of cattle farming in Sylhet, little is known about the prevalence of bovine Eimeria spp. and the risk factors connected with it. OBJECTIVES: We conducted a study to evaluate the prevalence, species diversity and associated risk factors of Eimeria spp. in a population of 50 cattle farms from 12 upazilas (sub-district) in Sylhet district. METHODS: Faecal samples were collected randomly from a total of 554 calves ranging in age from 1 month to 2 years old during a period of 7 months. We used Flotation and McMaster techniques for parasitological examination. Species identification was done by using their morphological and morphometric characteristics. RESULTS: Out of 554 calves, 308 were found to be positive for Eimeria species (55.60%). Seven species of Eimeria were identified. Among the identified species, E. bovis (38.98%), E. zuernii (26.17%) and E. alabamensis (22.38%) were found to be the most prevalent species. Mixed and species-specific Eimeria infection were (24.73%; 95% CI 21.32-28.49) and (30.87%; 95% CI 27.17-34.84), respectively. In addition, the highest prevalence was observed at Zakigonj (68%; 95% CI 58.34-76.33) and the lowest at Companygonj (40%; 95% CI 30.94-49.80). Eimeria species intensity ranged between 50 and 76,550 oocyst per gram of faeces. Analysis of associated risk factors by using multivariate logistic regression analysis revealed that age, gender and body condition were significantly (p < 0.05) associated with Eimeria infection. CONCLUSIONS: Based on these present findings, it can be assumed that 'coccidia belong to the most prevalent pathogens in the population of calves in the study area'. Thus, the findings of this study could be used as tools for adoptive surveillance and effective control and prevention of the disease in cattle populations in this region.

Isolation and characterization of novel reassortant mammalian orthoreovirus from pigs in the United States.

Mammalian orthoreovirus (MRV) infects multiple mammalian species including humans. A United States Midwest swine farm with approximately one thousand 3-month-old pigs experienced an event, in which more than 300 pigs showed neurological signs, like "down and peddling", with approximately 40% mortality. A novel MRV was isolated from the diseased pigs. Sequence and phylogenetic analysis revealed that the isolate was a reassortant virus containing viral gene segments from three MRV serotypes that infect human, bovine and swine. The M2 and S1 segment of the isolate showed 94% and 92% nucleotide similarity to the M2 of the MRV2 D5/Jones and the S1 of the MRV1 C/bovine/Indiana/MRV00304/2014, respectively; the remaining eight segments displayed 93%-95% nucleotide similarity to those of the MRV3 FS-03/Porcine/USA/2014. Pig studies showed that both MRV-infected and native contact pigs displayed fever, diarrhoea and nasal discharge. MRV RNA was detected in different intestinal locations of both infected and contact pigs, indicating that the MRV isolate is pathogenic and transmissible in pigs. Seroconversion was also observed in experimentally infected pigs. A prevalence study on more than 180 swine serum samples collected from two states without disease revealed 40%-52% positive to MRV. All results warrant the necessity to monitor MRV epidemiology and reassortment as the MRV could be an important pathogen for the swine industry and a novel MRV might emerge to threaten animal and public health.

Risk Assessment in Mining-Based Industrial Workers by Immunological Parameters as Copper Toxicity Markers.

BACKGROUND: Manifestation of certain health morbidity in copper dust-exposed subjects impels us to obtain a cogent view regarding the implicate relationship of immunoglobulin on health risk assessment in them. We present here immunological profile of copper pit worker and office employees residing in the vicinity. Rationale of this study is to delineate the risk factors involved for copper toxicity. MATERIALS AND METHODS: Copper mine workers (n = 87) were selected from a copper mine at Malanjkhand. Blood metal concentration and immunological profile such as IgG, IgM, IgA, and IgE were analyzed from these subjects. Data analysis was carried out using proper statistical tools. RESULTS: Chronically copper dust-exposed miners (N = 71) and office employees (N = 47) exhibited significantly higher contents of copper (P < 0.0001) when compared with normal control. Serum IgG and IgA were found to be elevated significantly (P < 0.0001) in them when compared with both office employees and normal control. Contrarily, significant decrease in serum IgM was observed in both the groups when compared with normal control (P < 0.0001). Serum IgE was found to be elevated more significantly only in miner when compared with normal control. Copper exhibited significant positive Pearson's correlation coefficient with IgE, IgG, and IgA (r = 0.39; r = 0.28; r = 0.21) but negative correlation (r = -0.39) with IgM. Odds ratio analysis validated that elevated levels of IgE in miner and decrease in levels of IgM in both groups were truly affected by increase in copper levels from normal to abnormal. CONCLUSION: Miners are prone to morbidity such as type 2 diabetes and respiratory discomfort (asthma and hypersensitivity) since imbalance in both IgM and IgE is known to be associated with such morbidity. Immunopathy observed in chronically exposed miners could be attributed to copper toxicity in them.

Follicular fluid dehydroepiandrosterone sulfate is a credible marker of oocyte maturity and pregnancy outcome in conventional in vitro fertilization cycles.

AIM: To investigate if the level of dehydroepiandrosterone sulfate (DHEA-s) in follicular fluid (FF) influences the competence of oocytes to fertilize, develop to the blastocyst stage, and produce a viable pregnancy in conventional in vitro fertilization (IVF) cycles. SETTINGS AND DESIGN: Prospective study of age-matched, nonpolycystic ovary syndrome (PCOS) women undergoing antagonist stimulation protocol involving conventional insemination and day 5 blastocyst transfer. MATERIALS AND METHODS: FF levels of DHEA-s and E2 were measured by a radio-immuno-assay method using diagnostic kits. Fertilization rate, embryo development to the blastocyst stage and live birth rate were main outcome measures. Cycles were divided into pregnant/nonpregnant groups and also into low/medium/high FF DHEA-s groups. Statistical analysis was done by GraphPad Prism V software. RESULTS: FF DHEA-s levels were significantly higher in pregnant (n = 111) compared to nonpregnant (n = 381) group (1599 ± 77.45 vs. 1372 ± 40.47 ng/ml; P = 0.01). High (n = 134) FF DHEA-s group had significantly higher percentage of metaphase II (MII) oocytes (91.5 vs. 85.54 vs. 79.44%, P < 0.0001), fertilization rate (78.86 vs. 74.16 vs. 71.26%, P < 0.0001), cleavage rate (83.67 vs. 69.1 vs. 66.17%, P = 0.0002), blastocyst formation rate (37.15 vs. 33.01 vs. 26.95%, P < 0.0001), and live birth rate (29.85 vs. 22.22 vs. 14.78%, P = 0.017) compared to medium (n = 243) and low (n = 115) FF DHEA-s groups, respectively despite comparable number of oocytes retrieved and number of blastocysts transferred. FF DHEA-s levels correlated significantly with the attainment of MII oocytes (Pearson r = 0.41) and fertilization rates (Pearson r = 0.35). CONCLUSION: FF DHEA-s level influences the oocyte maturation process and is predictive of fertilization, embryo development to the blastocyst stage and live birth rates in non-PCOS women undergoing conventional IVF cycles.

Periodicity in the levels of serum plasminogen activator inhibitor-1 is a robust prognostic factor for embryo implantation and clinical pregnancy in ongoing IVF cycles.

CONTEXT: Plasminogen activator inhibitor-1 (PAI-1) has been inversely correlated to proteolytic extracellular-matrix degradation exerted by urokinase-type (u-PA) and tissue-type plasminogen activators (t-PA). Any pathological disturbance in PAI-1 levels may lead to several pregnancy complications. AIMS: To assess the influence of periodicity in serum PAI-1 levels on embryo implantation and clinical pregnancy outcome in IVF cycles. SETTINGS AND DESIGN: Prospective study of 120 IVF cycles at private infertility centre. MATERIAL AND METHODS: Endometrial response (ER) assessment by measuring Endometrial thickness (cm) and echopattern (grade). Serum PAI-1(ng/ml) measurement by ELISA method on day of hCG, day of ET and days 7 and 14 of ET. Main outcome measure was clinical pregnancy. STATISTICAL ANALYSIS: Student "t" test, ANOVA, Post-test for linear trend, Pearson Correlation. RESULTS: PAI-1 levels declined from dhCG to dET (318.8 ± 36.1 to 176.1 ± 28.4) whereas they increased steadily from dET to d7 to d14ET (176.1 ± 28.4 to 285.2 ± 30.4 to 353.5 ± 150.4; P = 0.0004) in pregnant group (n = 31). Conversely, dhCG to dET levels increased in both nonpregnant (n = 75; 173.8 ± 18.3 to 280.8 ± 26.1) and biochemical pregnancy BCP (n = 14; 172.7 ± 31.1 to 216 ± 30.1) groups. The rising pattern from dET to d7 to d14ET was not observed in non-pregnant and BCP groups. ER thickness and grade shared significant correlation with serum PAI-1 on dET (Pearson r: ER = 0.28, Grade = 0.29) and d7ET (Pearson r: ER = 0.40, Grade = 0.23). CONCLUSIONS: Periodicity in serum PAI-1 levels offers a robust prognostic factor for predicting clinical pregnancy outcome. The dhCG to dET PAI-1 transition is a decisive factor for either transferring embryos in same/ongoing cycle or cryopreserving them and postponing ET to subsequent natural cycle.

Transfer of spontaneously hatching or hatched blastocyst yields better pregnancy rates than expanded blastocyst transfer.

CONTEXT: Blastocyst stage embryo transfer (ET) has become routine practice in recent years. However, probably due to limitations of assisted hatching techniques, expanded blastocyst transfer (EBT) is still the preferred mode. Inexplicably, not much consideration has been given to spontaneously hatching/hatched blastocyst transfer (SHBT). AIM: This study aimed to investigate developmental potential of spontaneously hatching/hatched blastocyst against EBT in in vitro fertilization (IVF) cycles. SETTINGS AND DESIGN: Prospective study of 146 women undergoing their first IVF- ET cycle. SUBJECTS AND METHODS: On the basis of blastocyst status, women were classified into SHBT and EBT groups. Intracytoplasmic sperm injection cycles were excluded to remove male factor bias. Implantation rate (IR), clinical pregnancy rate, and live birth rate were the main outcome measures. STATISTICAL ANALYSIS: Graph-pad Prism 5 statistical package. RESULTS: SHBT group showed significantly higher blastocyst formation rate (53.3 ± 17.5 vs. 43.1 ± 14.5%, P = 0.0098), top-quality blastocysts (71.8 vs. 53.7%, P = 0.0436), IR (43.6 vs. 27.9%, P = 0.0408), pregnancy rate (59.4 vs. 45.1%, P = 0.0173), and live birth rate (36.8 vs. 22.8%, P = 0.003) compared to EBT group. Multiple pregnancy rates remained comparable between the two groups. Implantation correlated strongly with top-quality blastocysts (Pearson, r = 0.4441) in SHBT group, while the correlation was nonsignificant in EBT group. CONCLUSION: Extending culture of expanded blastocysts by a few hours to allow transfer of spontaneously hatching/hatched blastocysts gives higher implantation and pregnancy rates with no added risk of multiple gestations. Spontaneously hatching/hatched blastocysts have a better potential to implant and develop into a positive pregnancy.

Follicular-fluid anti-Mullerian hormone (FF AMH) is a plausible biochemical indicator of functional viability of oocyte in conventional in vitro fertilization (IVF) cycles.

CONTEXT: Oocyte quality may be a governing factor in influencing in vitro fertilization (IVF) outcomes. However, morphological evaluation of oocyte quality is difficult in conventional IVF cycles. Follicular-fluid (FF), the site for oocyte growth and development, has not yet been sufficiently explored to obtain a marker indicative of oocyte quality. Anti-Mullerian hormone (AMH) is produced by granulosa cells of preantral and early-antral follicles and is released in FF. AIM: To investigate AMH as a biochemical indicator of functional viability/quality of oocyte produced in the FF micro-environmental milieu. SETTINGS AND DESIGN: Prospective study involving 132 cycles of conventional IVF-embryo transfer (ET) in infertile women. SUBJECTS AND METHODS: AMH concentration was estimated in pooled FF on day of oocyte pickup. Cycles were sorted into low and high groups according to median (50 (th) centile) values of measurement. Main outcome measure was oocyte viability, which included morphological assessment of oocyte quality, fertilization rate, clinical pregnancy, and implantation rates. STATISTICAL ANALYSIS: Graph-pad Prism 5 statistical package. RESULTS: Low FF AMH group shows significantly higher percentage of top-quality oocytes (65.08 ± 24.88 vs. 50.18 ± 25.01%, P =0.0126), fertilization (83.65 ± 18.38 vs. 75.78 ± 21.02%, P =0.0171), clinical pregnancy (57.57 vs. 16.67%, P >0.0001), and embryo implantation rates (29.79 vs. 7.69%, P >0.0001) compared to high FF AMH group. FF AMH shares an inverse correlation with FF E2 (Pearson r = -0.43, r(2) = 0.18) and clinical pregnancy (Pearson r = -0.46, r(2) = 0.21). Threshold value of FF AMH for pregnancy is >1.750 ng/mg protein. CONCLUSION: FF AMH is a plausible biochemical indicator of functional viability of oocyte in conventional IVF cycles.

Follicular fluid insulin like growth factor-1 (FF IGF-1) is a biochemical marker of embryo quality and implantation rates in in vitro fertilization cycles.

CONTEXT: Insulin-like growth factor-1 (IGF-1) has been reported to play a role in human follicular and embryonic development. However, earlier studies carried out mostly in animal models or in culture mediums supplemented with IGF-1 have been unable to directly link IGF-1 with embryo quality. Results correlating IGF-1 with pregnancy outcome have also been ambiguous so far. AIM: The aim of this study is to find if in situ follicular-fluid level of IGF-1 is predictive of embryo quality and implantation rates in in vitro fertilization (IVF) cycles. SETTINGS AND DESIGN: Prospective study involving 120 cycles of conventional IVF-embryo transfer in infertile women. SUBJECTS AND METHODS: IGF-1 concentrations were estimated in pooled follicular-fluid on the day of oocyte-pickup. Embryo quality was assessed daily at different developmental stages. Cycles were sorted into low and high follicular fluid insulin-like growth factor-1 (FF IGF-1) groups according to the median value of measurement. Embryo quality, clinical pregnancy and implantation rate were the main outcome measures. STATISTICAL ANALYSIS: Graph-pad Prism 5 statistical package. RESULTS: FF IGF-1 correlates with embryo quality (Pearson r = 0.3894, r (2) = 0.1516, P > 0.0001) and clinical pregnancy (Pearson r = 0.5972, r (2) = 0.36, P > 0.0001). High FF IGF-1 group shows significantly higher rates of fertilization, cleavage, blastocyst formation and top grade embryos compared with low FF IGF-1 group. Clinical pregnancy rates (38.33 vs. 20%, P = 0.0272) and embryo implantation rates (21.6 vs. 10.32%, P = 0.0152) are also significantly higher in the high versus low FF IGF-1 group. Threshold value of FF IGF-1 for clinical pregnancy is <58.50 ng/mg protein (receiver operating characteristics AUC : 0.85 ± 0.03, 95% CI: 0.78-0.91). CONCLUSION: FF IGF-1 is a plausible biochemical marker of embryo quality and implantation rate and correlates with clinical pregnancy rates in conventional IVF cycles.

An overview of caspase: Apoptotic protein for silicosis.

Silicosis is a chronic lung disease characterized by granulomatous and fibrotic lesions, which occurs due to accumulation of respirable silica mineral particles. Apoptosis is an important phenomenon of cell death in silicosis. The relationship between silica dust and its exposure is well established. But, the complex chain of cellular responses, which leads to caspase activation in silicosis, has not been fully discovered. Caspase activation plays a central role in the execution of apoptosis. Silica-induced apoptosis of the alveolar macrophages could potentially favor a proinflammatory state, occurring in the lungs of silicotic patients, resulting in the activation of caspase prior to induction of the intrinsic and extrinsic apoptosis pathways. Recent studies indicated that apoptosis may involve in pulmonary disorders. This review summarizes the current knowledge about the underling mechanism of biochemical pathways in caspase activation that have been ignored so far in silicosis. In addition, caspase could be a key apoptotic protein that can be used as an effective biomarker for the study of occupational diseases. It may provide an important link in understanding the molecular mechanisms of silica-induced lung pathogenesis.

Detection of tissue origin of a 43 kDa diabetogenic protein from alloxan-induced diabetic rats.

BACKGROUND: Earlier, we had found high levels of circulating immune complexes (CICs) in the serum of type 2 diabetes mellitus patients along with a novel 43 kDa protein. METHODS: Different tissues of alloxan-induced, diabetic, male albino rats (200-250 g in body weight) were collected for the present study. Tissue proteins were isolated and separated by 10% SDS-polyacrylamide gel electrophoresis (SDS-PAGE). A primary cell culture of polymorphonuclear neutrophils (PMNs) was used to evaluate the effects of the diabetogenic protein. Cell proliferative index, oxidant/antioxidant status, and ion-transporting ability were chosen as study parameters. RESULTS: SDS-PAGE of different tissues shows that the diabetic liver alone was the only tissue that contained the 43 kDa protein band compared to the normal liver. In vitro effects of the new liver protein on PMNs include significantly decreased cell proliferative activity, increased free radical levels, and decreased levels of antioxidant enzymes as well as ionic transporters. The new liver protein also exhibited protease activity when compared with standard trypsin. CONCLUSIONS: This study concluded that a novel 43 kDa protein obtained from the livers of alloxan-induced diabetic rats shows protease activity as well as antiproliferative activity. Also, this protein may act as a diabetogenic factor as it elicited a significantly gross elevation in the oxidant status level as well as in the levels of lysosomal enzymes and a decrease in the levels of antioxidative enzymes and ionic transporters of PMNs.

Antidiabetic and antioxidant effects of Picrorhiza kurrooa rhizome extracts in diabetic rats.

Picrorhiza kurrooa is mentioned in Ayurveda for the treatment of many disorders, but it has not been subjected to systematic scientific investigations to assess its antidiabetic effect. The oral administration of aqueous and methanol extracts of P. kurrooa rhizomes (250 and 500 mg / kg body weight / day) for 15 days significantly reduced blood glucose, glycosylated haemoglobin and increased total hemoglobin, plasma insulin in alloxan-induced diabetes in albino rats. The treatment also showed significant correction in the level of nitric oxide radicals, superoxide radicals, peroxynitrite radical, lipid peroxidation, glutathione, glutathione reductase, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase and catalase in the pancreas of alloxan diabetic rats.