Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs.

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.

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.

Exploration of allelic variants in short tandem repeats (STRs) flanking milk production QTLs and their association with milk production traits in Indian water buffaloes.

Short tandem repeats (STRs) are co-dominant, highly polymorphic marker loci, distributed throughout the genome and useful for identification and mapping of QTLs associated with variation in traits of economic significance. Allelic variants were identified in STRs located in close vicinity of cattle QTLs for milk production,, viz. BMS713, BM6404, BM4513, BM121, BM6105, TGLA245, BL1100, BMS1948, BMS711, BM1443, BM1706, BM6438, BM143, BM415, ETH131, ETH 2, and BM1329 in 109 water buffaloes of Murrah breed. All loci except TGLA245 exhibited polymorphism of varying degree. The observed number of alleles, effective number of alleles, PIC value, observed heterozygosity, and expected heterozygosity across all STR loci averaged 4.12 ± 0.22, 3.20 ± 0.22, 0.60 ± 0.04, 0.34 ± 0.05, and 0.66 ± 0.03, respectively. Goodness of fit (chi-square) and likelihood ratio (G square) test demonstrated that the population exhibited a deviation from HWE for all the loci. FIS was positive and ranged from 0.22 to 1.00. Least square analysis of variance exhibited significant effects of BM4513, ETH131, BM713, and BM6105 on first lactational total lactation milk yield, 305-day milk yield, lactation length, and dry period respectively. None of the STRs could exhibit significant effect on peak yield.

Genetic control of non-genetic inheritance in mammals: state-of-the-art and perspectives.

Thought to be directly and uniquely dependent from genotypes, the ontogeny of individual phenotypes is much more complicated. Individual genetics, environmental exposures, and their interaction are the three main determinants of individual's phenotype. This picture has been further complicated a decade ago when the Lamarckian theory of acquired inheritance has been rekindled with the discovery of epigenetic inheritance, according to which acquired phenotypes can be transmitted through fertilization and affect phenotypes across generations. The results of Genome-Wide Association Studies have also highlighted a big degree of missing heritability in genetics and have provided hints that not only acquired phenotypes, but also individual's genotypes affect phenotypes intergenerationally through indirect genetic effects. Here, we review available examples of indirect genetic effects in mammals, what is known of the underlying molecular mechanisms and their potential impact for our understanding of missing heritability, phenotypic variation. and individual disease risk.

Binge drinking, HIV/HPV co-infection risk, and HIV testing: Factors associated with HPV vaccination among young adults in the United States.

Human papillomavirus (HPV) is a common sexually transmitted infection. Binge drinkers often engage in HIV/HPV co-infection high-risk behaviors. We examined the association between binge drinking, HIV/HPV co-infection risk, HIV testing and HPV vaccination among young adults. Data from the 2017 Behavioral Risk Factor Surveillance System survey were examined. Participants (N = 430/450,016; 0.11%) were HPV vaccine-eligible young adults ages 18-26 years. Multivariable logistic regression examined the association between binge drinking in the past 30 days, HIV/HPV co-infection high-risk risk behaviors, HIV testing, and HPV vaccination (initiated/completed, unvaccinated) among young adults. Respondents were primarily cisgender (99.8%), non-Hispanic White (41.4%), employed (46.2%) or student (35.4%), and insured (68.2%). Most did not binge drink (55.2%). The majority did not engage in HIV/HPV co-infection high-risk risk behaviors (78.2%). More than one-half had never been tested for HIV (59%) nor vaccinated against HPV (60.6%). Although binge drinkers (44.8%) were significantly more likely to engage in HIV/HPV co-infection high-risk behaviors (OR = 2.1; 95% CI: 1.0-4.5), binge drinking was not positively associated with HIV testing (OR = 0.98; 95% CI: 0.63-1.53). After adjusting for demographics and HIV/HPV co-infection high-risk behaviors, one (aOR = 2.71; 95% CI: 1.11-6.65) and two episodes (aOR = 3.05; 95% CI: 1.26-7.41) of binge drinking in the past 30 days were significantly associated with HPV vaccination uptake. Positive associations between HPV vaccination and participants having an HIV test in 2017 (aOR = 3.86; 95% CI: 1.42-10.55) and before 2017 (aOR = 2.62; 95% CI: 1.23-5.56) were also statistically significant. Because young adult binge drinkers are more likely to engage in HIV/HPV co-infection high-risk behaviors, promoting HPV vaccination and HIV testing are important public health objectives.

Glaucoma awareness Indian military personnel: a tri-service study.

INTRODUCTION: In India, glaucoma is the third most common cause of blindness, reflecting both its asymptomatic presentation and a lack of knowledge in the general population. No previous published data of glaucoma awareness among the Indian Armed forces personnel exists, who constitute a unique group consisting of people drawn from all parts of the country and society. METHODS: Bilingual questionnaires were distributed to 496 serving Army, Navy and Air Force personnel serving in units local to the Zonal military hospital in North India. Having heard of the term glaucoma resulted in the subject being 'glaucoma aware', while 'knowledge of glaucoma' required at least three out of six questions to be answered correctly. RESULTS: 110/496 (22%) participants were found to be glaucoma aware, while knowledge of glaucoma was found in 60/496 (12%) participants. CONCLUSIONS: This study demonstrates that glaucoma awareness and knowledge is high compared with rural or urban Indian populations. This is likely reflects the frequent health camps conducted by the armed forces and periodic medical examinations. However, these figures are still low compared with developed countries and likely reflects differences in education standards, socioeconomic status and differing influences of the media.

Perioperative management of a patient with Dandy Walker malformation with tetralogy of Fallot undergoing total correction and fresh homologous pericardial pulmonary valve conduit implantation: Report of a rare case.

Perioperative management of a patient with Dandy-Walker malformation (DWM) with tetralogy of Fallot (TOF), patent ductus arteriosus, and pulmonary artery stenosis is a great challenge to the anesthesiologist. Anesthetic management in such patients can trigger tet spells that might rapidly increase intracranial pressure (ICP), conning and even death. The increase in ICP can precipitate tet spells and further brain hypoxia. To avoid an increase in ICP during TOF corrective surgery ventriculo-peritoneal (VP) shunt should be performed before cardiac surgery. We present the first case report of a 11-month-old male baby afflicted with DWM and TOF who underwent successful TOF total corrective surgery and fresh autologous pericardial pulmonary valve conduit implantation under cardiopulmonary bypass after 1 week of VP shunt insertion.

Healed perivalvular abscess: Incidental finding on transesophageal echocardiography [corrected].

A 36-year-old male patient presented with the complaints of palpitations and breathlessness. Preoperative transthoracic echocardiography (TTE) revealed a bicuspid aortic valve; severe aortic regurgitation with dilated left ventricle (LV) and mild LV systolic dysfunction (ejection fraction 50%). He was scheduled to undergo aortic valve replacement. History was not suggestive of infective endocarditis (IE). Preoperative TTE did not demonstrate any aortic perivalvular abscess. Intraoperative transesophageal echocardiography (TEE) examination using the mid-esophageal (ME) long-axis view, showed an abscess cavity affecting the aortic valve, which initially was assumed to be a dissection flap, but later confirmed to be an abscess cavity by color Doppler examination. The ME aortic valve short-axis view showed two abscesses; one was at the junction of the non-coronary and left coronary commissure and the other one above the right coronary cusp. Intraoperatively, these findings were confirmed by the surgeons. The case report demonstrates the superiority of TEE over TTE in diagnosing perivalvular abscesses.

Resumption of ovarian cyclicity and fertility response in bull-exposed postpartum buffaloes.

A study was undertaken to evaluate the effect of bull exposure on resumption of ovarian cyclicity and fertility response in postpartum buffaloes raised under standard farm conditions. A total of 24 Murrah buffaloes was randomly grouped to receive one of the following treatments: (1) exposure to a vasectomised bull from 40th to 90th day postpartum (bull-exposed, BE, n=11) and (2) isolated from bull (non-exposed, NE, n=13). Changes in the progesterone concentration were used to assess the resumption of ovarian cyclicity. Postpartum interval to resumption of ovarian cyclicity (47+/-2.58 days vs. 56+/-2.37 days, p<0.05) as well as behavioral estrus (57+/-3.61 days vs. 71+/-5.13 days, p<0.05) was shorter in bull-exposed animals than control animals. Similarly, animals in the BE group had significantly shorter interval to postpartum ovulation (48+/-2.69 days vs. 57+/-2.37 days, p<0.05). Reduced incidence of silent ovulation was observed in BE group compared to NE group (18.18% vs. 50%). More than half proportion of animals in BE group conceived by 60 days postpartum compared to a very low proportion of animals in NE group (54% vs. 15%, p<0.05). Furthermore, first service conception rate in BE animals was significantly greater than NE animals (100% vs. 37.50%, p<0.05). In conclusion, continuous bull exposure to buffaloes during later postpartum period accelerates resumption of ovarian cyclicity, reduces incidence of silent ovulation and enhances first service conception rate. These results indicate that introduction of bulls to buffalo herd could be a rational management strategy for reducing the postpartum anestrus by enhancing reproductive function in buffaloes.

Evaluation and comparison of early hemodynamic changes after elective mitral valve replacement in patients with severe and mild pulmonary arterial hypertension.

OBJECTIVE: To evaluate and compare early hemodynamic changes after elective mitral valve replacement (MVR) in patients with severe and mild pulmonary arterial hypertension (PAH). DESIGN: A prospective observational study. SETTING: University-affiliated hospital. PARTICIPANTS: Sixty patients undergoing elective MVR. INTERVENTIONS: The patients were divided into 2 equal groups based on the presence (group A) or absence (group B) of severe PAH defined as systolic pulmonary artery pressure (PAP) > or = 50 mmHg on preinduction pulmonary artery catheterization. Thiopental, fentanyl, midazolam, isoflurane, and rocuronium (or vecuronium if the heart rate >100 beats/min) were used for the induction and maintenance of anesthesia. MVR was performed using standard cardiopulmonary bypass (CPB) techniques. The therapy for PAH was electively instituted in all patients with a nitroglycerin infusion (0.5-1 microg/kg/min), deliberate hypocarbia (arterial carbon dioxide tension < or = 35 mmHg), fractional inspired oxygen concentration = 1.0, and elective ventilation for at least 12 hours in the postoperative period. Hemodynamic and arterial blood gas parameters were serially measured before induction; after intubation; after termination of CPB; after extubation; and at 6, 24, and 48 hours after surgery. Differences in these parameters were analyzed within and among the groups using appropriate statistical tests. MEASUREMENTS AND MAIN RESULTS: The mean CPB and aortic cross-clamp times were similar in the 2 groups (78 +/- 33 and 50 +/- 21 minutes in group A and 63 +/- 32 and 41 +/- 23 minutes in group B). The mean PAP, pulmonary capillary wedge pressure, and pulmonary vascular resistance decreased significantly soon after CPB in both groups (p < 0.001), but the decrease was significantly lower in group A (p < 0.001). The mean PAP approached near-normal values in group A (23 +/- 8 mmHg) and normal values in group B (16 +/- 6 mmHg) immediately postoperatively. There was an increase in cardiac index (p < 0.01) after CPB in group A. A relative improvement in oxygenation occurred after MVR in group A compared with group B (p < 0.001). Patients in group A were ventilated for a longer duration (25.9 +/- 18.8 v 17.3 +/- 7.9 hours, p < 0.05). There was no significant difference in the inotropic requirement between the 2 groups. There was no mortality in either group. CONCLUSIONS: PAP returns to near-normal values in patients with severe preoperative PAH and to normal values in patients with mild preoperative PAH immediately after MVR. The outcome after surgery in patients with severe PAH is comparable to those with mild PAH.

Length of insertion for pulmonary artery catheters to locate different cardiac chambers in patients undergoing cardiac surgery.

BACKGROUND: Although, guidelines related to length of insertion of a pulmonary artery catheter to reach a particular cardiac chamber are available, these are not backed by clinical studies. We measured the length of insertion of pulmonary artery catheters to locate the right ventricle, pulmonary artery and pulmonary capillary wedge positions in 300 adult patients undergoing elective cardiac surgery. METHODS: The pulmonary artery catheters were inserted using a standard technique through the right internal jugular vein. The right ventricle, pulmonary artery and wedge position of the catheter were confirmed by the characteristic waveforms, and the length of insertion to these points was measured. RESULTS: The right ventricle was reached at 24.6 (3) cm (95% CI 24.2-24.9 cm), pulmonary artery at 36 (4) cm (95% CI 35.6-36.5 cm) and wedge position at 42.8 (5.7) cm (95% CI 42.2-43.5 cm). The length of catheter to reach the right ventricle, pulmonary artery and wedge position was significantly more in patients undergoing valve surgery as compared with those undergoing coronary artery bypass grafting [26 (3.8) and 24 (2.5) cm; 38.5 (4.6) and 35 (3.2) cm; and 47.8 (6.9) and 41.2 (4.1) cm, respectively, P<0.001]. The length of insertion to reach pulmonary artery and pulmonary capillary wedge position was directly related to height of the patient (Pearson's correlation 0.157 and 0.15, respectively). CONCLUSIONS: We have provided the norms related to length of insertion of pulmonary artery catheter, which should be useful in accurate placement of the catheter and minimize complications related to coiling of the catheter.

Pulmonary artery catheter placement in high-risk coronary artery bypass grafting: should it be done before or after induction of anaesthesia?

Pulmonary artery catheter (PAC) is generally inserted after induction of general anaesthesia (GA). However, in high-risk coronary artery disease patients (left main disease / ejection fraction (35%), it may be desirable to insert it before the induction of GA. Thirty patients with left main coronary artery disease and / or left ventricular ejection fraction < 35% undergoing coronary artery bypass grafting (CABG) surgery were prospectively randomized into 2 groups of 15 each. In group A, pulmonary artery catheter was inserted before induction and in group B, after induction of GA. Haemodynamic parameters like heart rate (HR), mean arterial pressure (MAP), cardiac index (CI) and other derived parameters were obtained serially up to 10 min after tracheal intubation in group A and the haemodynamic management was based on these parameters. In group B, the haemodynamic management was based on HR and MAP. The demographic data was similar in both the groups. The time required for insertion of PAC was also similar in the two groups (7.6 +/- 1.8 and 6.2 +/- 1.3 min, p > 0.05). The number of interventions in the form of infusions of volume, nitroglycerin or dopamine were significantly more in group A before tracheal intubation. The patients in group A maintained better haemodynamics at 10 min after tracheal intubation as compared with group B (CI 2.8 +/- 0.67 vs 2.1 +/- 0.49, p < 0.05; stroke volume 54 +/- 18 vs 51 +/- 0.65, p < 0.05; systemic vascular resistance 1431 +/- 409 vs 1724 +/- 430, p < 0.05; pulmonary vascular resistance 109 +/- 34 vs 181 +/- 110, p < 0.05). Insertion of PAC before induction of GA provides informative data and can be utilized to treat haemodynamic alterations in high-risk patients undergoing CABG.

Effect of muscle relaxants on heart rate, arterial pressure, intubation conditions and onset of neuromuscular block in patients undergoing valve surgery.

Sixty six patients undergoing elective valve surgery were randomized to receive rocuronium bromide 0.6 mg/Kg (Group R, n=22), pancuronium bromide 0.1 mg/Kg (Group P, n= 22) and vecuronium bromide 0.1 mg/Kg (Group V, n=22), Measurements of heart rate and arterial pressure (systolic, diastolic and mean) were noted at the following stages: 1) baseline when haemodynamics were stable for 2 minutes after induction of anaesthesia (2) one, (3) three, (4) five minutes after administration of muscle relaxants, (5) One, (6) three, and (7) five minutes after intubation. In group R, the heart rate decreased 5 min after injection of muscle relaxant from 93.9 +/- 21.3 to 82.4 +/- 20.7 beats/min (p<0.001). However, it increased to 128.3 +/- 25.8 beats/min (p<0.001) following intubation and returned to baseline at 5 min after intubation. In group P, heart rate increased from 98.8 +/- 32.6 to 109.6 +/- 32.7 beats/min (p<0.001), 1 min after injection of pancuronium and this increase persisted throughout the study period. In group V, heart rate decreased from 99.9 +/- 22.3 to 83.8 +/-19.6 beats/min (p<0.001) at 5 min after injection of the drug. It increased to 118.6 +/- 22.4 beats/min (p<0.001), 1 min after intubation and returned to baseline at 5 min after intubation. The decrease in heart rate in group R and V was accompanied by a significant decrease in systolic, diastolic and mean arterial pressure. In group P, only the systolic pressure decreased significantly at 5 min after injection of the drug. Intubation was accompanied by a significant increased in systolic, diastolic and mean arterial pressure in all the groups. Excellent intubation conditions (intubation score 3-4) were observed with all the three drugs, however, there were number of patients in group P who showed diaphragmatic movement during intubation. Onset of action of muscle relaxant, was fastest with rocuronium (group R=132.7 +/- 0.3 sec, P=182.6 +/- 68.5 sec, V= 144.8 +/- 46.1 sec, Group P vs Group R). To conclude, pancuronium causes significant increase in heart rate and should be preferred in patients with regurgitant lesions having slower baseline heart rate. Vecuronium and rocuronium decrease the heart rate and should be preferred in patient with faster baseline heart rate. In terms of intubating conditions rocuronium and vecuronium provide best conditions, but onset is faster with rocuronium.

Surgical interventions in patients undergoing percutaneous balloon mitral valvotomy: a retrospective analysis of anaesthetic considerations.

Between 1990 and 2000, 5499 balloon mitral valvotomies were performed at GB Pant Hospital. Amongst these, 45 patients required surgical intervention, which form the basis of this report. There were 18 males and 27 females with the mean age of 26.5+/-8.3 years and weight of 42.9+/-7.39 kg. Thirty-five patients underwent open-heart surgery and 10 closed-heart surgery. Twenty-five patients developed acute severe mitral regurgitation during balloon mitral valvotomy and required emergency open-heart surgery. Morphine based anaesthetic technique with careful attention to haemodynamic monitoring was used in these patients. All patients required a high inotropic support to terminate the cardiopulmonary bypass. The closed-heart surgical procedures included emergency exploration for cardiac tamponade (4), exploration + closed mitral valvotomy (4), and elective closed mitral valvotomy (2). The overall mortality was 9%, which is much higher than the reported mortality for elective mitral valve replacement. Morphine based anaesthetic technique is useful in these patients. Adequate oxygenation, vasodilators, inotropes and diuretics are required for preoperative stabilisation of patients who develop acute mitral regurgitation, while those who develop cardiac tamponade need volume replacement along with inotropes and immediate surgical decompression of the tamponade.

The effect of acetate pathway mutations on the production of pyruvate in Escherichia coli.

We compared pyruvate accumulation in six strains of Escherichia coli and their corresponding ppc mutants. Each strain contained a mutation of a gene involved in the pathway to acetate synthesis. Strains with mutations in genes encoding the pyruvate dehydrogenase complex generally exhibited the greatest pyruvate accumulation of which CGSC6162 (an aceF mutant) and CGSC6162 Delta ppc were studied in greater detail in controlled fermenters. Both CGSC6162 and CGSC6162 Delta ppc accumulated greater than 35 g/l pyruvate in a medium supplemented with acetate. We observed pyruvate mass yields from glucose of 0.72 in CGSC6162, with volumetric productivities above 1.5 g l(-1) h(-1). For CGSC6162 Delta ppc, we observed pyruvate yields of 0.78 and volumetric productivities above 1.2 g l(-1) h(-1). CGSC6162 consumed all initially supplied acetate, while CGSC6162 Delta ppc first consumed and then generated acetate during the course of a 36 h fermentation. Acetate generation and pyruvate oxidase activity was pH- and temperature-dependent, with a pH of 7.0 and the lowest temperature studied (32 degrees C) favoring the greatest pyruvate generation. Lactate was an unexpected by-product even though measured lactate dehydrogenase (LDH) activity was very low.

Atrial ECG as a guide to the placement of central venous catheter in patients undergoing Open Heart Surgery.

Hundred adults undergoing open heart surgery were randomized into two equal groups. In group I (n=50), surface anatomical landmarks and in group II (n=50) atrial ECG was used as a guide for correct placement of the central venous catheter (within 1 cm of superior vena cava - right atrial junction). The position of the catheter tip was confirmed by direct palpation by the surgeon on the operating table and by radiological examination in the post operative period. Surgeon's assessment revealed that the catheter was successfully placed in 32 (69.6%) patients in group II and 25 (50%) patients in group I (p=NS). Radiological examination revealed that the catheter was successfully placed in 31 (67.4%) patients in group II and in 28 (57.1%) patients in group I (p=NS). Amongst the unsuccessful placements right atrial placement was present in 5 patients (10%) in group I and 7 patients (15.2%) in group II by surgeon's assessment and 8 patients (16.3%) in group I and 9 patients (9.6%) in group II by radiological examination (p=NS) No complications related to intracardiac placement occurred in any of the patients. We conclude that atrial ECG is a promising technique for central venous catheter placement, although it did not significantly increase the correct placement in this study. This may be due to alteration in the relationship of sino-atrial node and superior vena cava - right atrial junction in patients with cardiac disease. Further studies defining the correct technique of insertion, (especially in cardiac patients) are necessary to improve the success rate.