Increased homozygosity due to endogamy results in fitness consequences in a human population.

Recessive alleles have been shown to directly affect both human Mendelian disease phenotypes and complex traits. Pedigree studies also suggest that consanguinity results in increased childhood mortality and adverse health phenotypes, presumably through penetrance of recessive mutations. Here, we test whether the accumulation of homozygous, recessive alleles decreases reproductive success in a human population. We address this question among the Namibian Himba, an endogamous agro-pastoralist population, who until very recently practiced natural fertility. Using a sample of 681 individuals, we show that Himba exhibit elevated levels of "inbreeding," calculated as the fraction of the genome in runs of homozygosity (FROH). Many individuals contain multiple long segments of ROH in their genomes, indicating that their parents had high kinship coefficients. However, we do not find evidence that this is explained by first-cousin consanguinity, despite a reported social preference for cross-cousin marriages. Rather, we show that elevated haplotype sharing in the Himba is due to a bottleneck, likely in the past 60 generations. We test whether increased recessive mutation load results in observed fitness consequences by assessing the effect of FROH on completed fertility in a cohort of postreproductive women (n = 69). We find that higher FROH is significantly associated with lower fertility. Our data suggest a multilocus genetic effect on fitness driven by the expression of deleterious recessive alleles, especially those in long ROH. However, these effects are not the result of consanguinity but rather elevated background identity by descent.

High rate of extrapair paternity in a human population demonstrates diversity in human reproductive strategies.

Among nonhuman species, social monogamy is rarely accompanied by complete fidelity. Evolutionary theory predicts that the rate of extrapair paternity (EPP) should vary according to socioecological conditions. In humans, however, geneticists contend that EPP is negligible and relatively invariable. This conclusion is based on a limited set of studies, almost all of which describe European-descent groups. Using a novel, double-blind method designed in collaboration with a community of Himba pastoralists, we find that the rate of EPP in this population is 48%, with 70% of couples having at least one EPP child. Both men and women were very accurate at detecting cases of EPP. These data suggest that the range of variation in EPP across human populations is substantially greater than previously thought. We further show that a high rate of EPP can be accompanied by high paternity confidence, which highlights the importance of disaggregating EPP from the notion of "cuckoldry."

Antidiabetic and antioxidant potentials of Euphorbia hirta leaves extract studied in streptozotocin-induced experimental diabetes in rats.

Euphorbia hirta, commonly known as asthma weed, is a popular folk remedy for the treatment of various ailments. Recent studies have indicated that plant has potent antioxidant properties. As part of an ongoing programme to validate the use of some reputed herbs in Indian traditional medicines, the present study was aimed to evaluate the antidiabetic and antioxidant potentials of E. hirta leaves in streptozotocin-induced experimental diabetes in rats. Oral administration of E. hirta leaves extract (300 mg/kg b.w./rat/day) for a period of 30 days indicated the antidiabetic nature of the leaves extract. Determination of the lipid peroxides, hydroperoxides, and both enzymatic and non-enzymatic antioxidants evidenced the antioxidant potential of the leaves extract. Assay of enzymes such as serum aspartate transaminase (AST), serum alanine transaminase (ALT) and serum alkaline phosphatase (ALP) revealed the non-toxic nature of E. hirta leaves. The hypoglycemic activity of the leaves extract was comparable with gliclazide, a standard reference drug.

Phase II clinical trial with Praneem polyherbal tablets for assessment of their efficacy in symptomatic women with abnormal vaginal discharge (an ICMR task force study).

Abnormal vaginal discharge syndrome (AVDS) is a commonly observed gynaecological complaint for which women seek medical attention. The present study was conducted in six Indian Council of Medical Research centres with Praneem polyherbal tablets (PPT), to determine their efficacy in the treatment of symptomatic women with AVDS. Data are given on 141 subjects investigated. In total, 137 women (97%) reported complete (n=62, 44%) and partial (n=75, 53%) relief from symptoms after use of PPT for seven consecutive days. On speculum examination, 71 (74%) women were confirmed to be cured of AVDS. Microbiological tests could only be conducted microscopically for Trichomonas vaginalis, Candida albicans and bacterial vaginosis. It was observed that all women with T. vaginalis had this infection cured by PPT, and the cure rate was 77% for C. albicans and 68% for bacterial vaginosis. Seventy-eight women (55%) reported a transient burning sensation, mostly on the first 2 d of intake of PPT; however, they continued to use the tablets for the prescribed 7 d. This study lays the basis for an extended Phase II/III clinical trial, preferably randomized and comparing a larger number of women to confirm the safety and efficacy of PPT.

Estrogen receptor beta1 and the beta2/betacx isoforms in nonneoplastic endometrium and in endometrioid carcinoma.

Estrogen receptor beta (ERbeta) has five carboxyl-terminal (C-terminal) isoforms derived from alternative splicing. ERbeta1 is the wild-type receptor whereas ERbeta2/betacx lacks the activation function (AF)-2 core essential for ligand-dependent transcriptional activation and so behaves as a dominant-negative receptor affecting the function of ERalpha. The objective of this study was to analyze the expression of ERbeta1 and ERbeta2/betacx isoforms in nonneoplastic endometrium and endometrioid carcinoma. The study was conducted on samples of 22 proliferative endometrium, 15 secretory endometrium, 20 simple hyperplasia (without atypia), and 26 endometrioid carcinomas. The transcript and protein levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. For the detection of ERbeta2/betacx protein, a polyclonal antibody was raised to its unique C-terminus, characterized, and used in immunohistochemistry. The two ERbeta isoforms are expressed in the proliferative and secretory phase endometrium with no significant change in their relative levels. The levels of the ERbeta1 isoform were lower as compared to the levels of ERbeta2 in all the groups studied. Expression of ERbeta2/betacx was decreased in endometrioid carcinoma as compared to proliferative endometrium (P < 0.01). A significant decrease of the ERbeta2/ERbetacx transcript was observed with higher grade tumors (P = 0.041). Progesterone receptor (PR) expression was not influenced by either of the ERbeta isoforms which was observed by logistic regression analysis in all the groups. The coexpression of ERbeta2/betacx with ERalpha did not affect PR levels (logistic regression analysis). Thus, we conclude in the human endometrium, there is significant ERbeta2/betacx isoform expression and alterations in its levels could be involved in endometrial cancer progression.

A polyherbal vaginal pessary with spermicidal and antimicrobial action: evaluation of its safety.

A polyherbal vaginal pessary (Praneem) has been formulated that has antimicrobial properties against genital pathogens in addition to spermicidal action. Thus, it has dual potential as a barrier method for contraception and for providing protection against some sexually transmitted infections. The present study reports the findings of a multicentre trial that was conducted to evaluate the safety of this product. Trials were carried out in 23 women in three centres in India: the Postgraduate Institute of Medical Education and Research, Chandigarh; Safdarjang Hospital, New Delhi; and Kamla Nehru Memorial Hospital, Allahabad. Thorough clinical and pelvic examinations were carried out as well as cervical cytology, blood biochemistry and haematology before and after use of the polyherbal pessary intravaginally once daily for 7 consecutive days. No toxicity was observed on clinical examination or by laboratory investigations. Daily intravaginal use of this pessary for 7 days had no adverse effects on cervical cytology or on metabolic and organ functions.

Vehicle interior interactions and kinematics of rear facing child restraints in frontal crashes.

The performance of rear facing child restraints in frontal crashes can be determined by controlling a) the child's kinematics and b) interactions with vehicle structures. Twelve sled tests were performed to analyze the effect of the location and structural properties of vehicle interior components. The role of restraint kinematics was studied by developing computational models which underwent idealized motions. Stiff structures originally offset from the restraint, but which contact the restraint late in the test, cause increased injury values. Attachment methods which reduce child restraint rotation and more rigidly couple the restraint to the vehicle result in the best safety performance.

Abortion procedures in a tertiary care institution in India.

OBJECTIVE: To determine the complications rate of termination of pregnancy (TOP) and the risk factors for complications following TOP. METHODS: Retrospective observational study of the records of 1287 women who underwent TOP in the Department of Obstetrics and Gynaecology of the Postgraduate Institute of Medical Education and Research, Chandigarh, India, between 1997 and 2001. First-trimester abortion was performed in 1088 women (85%) and second-trimester abortion in 199 women (15%). Most women (76%) were aged between 26 and 30 years; they were educated and requested TOP primarily to limit the number of their children or to space their births. A malformed fetus was the indication for TOP in 5.9% cases, and 16% of the women had medical disorders associated with the pregnancy. Suction evacuation was the method of choice for first-trimester abortion (88%); dinoprostone gel and extra-amniotic saline solution plus oxytocin infusion were the primary methods (71%) for second-trimester abortion. RESULTS: Uterine perforation occurred in 1 patient (0.09%) after a first-trimester abortion. The total rate of complications was 3.79% after first-trimester and 4.0% after second-trimester abortions. Excessive hemorrhage and retained placenta were chief complications associated with second-trimester abortion. Incomplete abortion (1.5%) and minor infection were seen in 2.3% patients. The rate of complications was higher among parous women. Postabortion insertion of a CuT intrauterine device increased the need for a second course of antibiotics. CONCLUSION: Termination of pregnancy is safe if adequate care is taken while performing the procedure.

Psychological aspects of infertility due to various causes--prospective study.

SUBJECTS AND METHODS: One hundred and twenty infertile couples (30 each among unexplained infertility, anovulation, tubal factor, and male factor groups) and 30 fertile couples as controls were evaluated for psychological assessment by different psychological test instruments. Initial evaluation was done at recruitment, followed by reassessment at 3, 6, 9 and 12 months during the infertility work-up, and at the end when the specific diagnosis and the management and prognosis were disclosed. RESULTS: Psychological components were found to play a significant role in infertility of unknown etiology, especially in the male partner. They affected the personality and social behavior of the male partner and caused anxiety, but led to depression in the female partner. In cases of organically caused infertility, partners were worried about the other's reaction. Anxiety was significantly greater in the partner with the fertility problem than in the other partner. Life events were significant in the partner in whom the fertility problem was detected. Periodic psychological assessment was not affected by infertility work-up on the male partner in any of the groups, whereas anovulation and tubal factor infertility showed a significant psychological effect on the female partner at the end of work-up. Depression and anxiety in the female partner were evident soon after the investigation started.

Analgesic efficacy of intramuscular opioids versus epidural analgesia in labor.

OBJECTIVES: To compare analgesic efficacy of intramuscular opioids: meperidine and tramadol with epidural analgesia. METHODS: One hundred and twenty-eight term nulliparous women with singleton pregnancy and vertex presentation were randomized to receive either epidural (n=43), meperidine (n=39) or tramadol (n=44). A visual analog scale (VAS) was used to assess the severity of pain. The parameters analyzed were analgesic efficacy, effect on labor, other maternal side effects, perinatal outcome and maternal satisfaction. RESULTS: Median VAS scores following first dose were 0 (0-5), 5 (3-8) and 5 (3-8) in epidural, meperidine and tramadol groups, respectively. Ninety percent of women rated analgesia as good to excellent in the epidural group as compared with 72% of women in the meperidine group and 65% in tramadol group. However, epidural caused a significant prolongation of first (P<0.05) and second (P<0.01) stage of labor with an increased number of operative deliveries (27% in the epidural, 7.6% in the meperidine, and 11.4% in the tramadol groups, P<0.05). In the epidural group 40% women had urinary retention and 16% had motor weakness, whereas sedation was the only side effect seen in the meperidine (41%) and tramadol groups (9%). Respiratory depression was noted among three neonates in the meperidine group, two in the tramadol group and none in the epidural group. CONCLUSIONS: The analgesic efficacy and maternal satisfaction is better with epidural analgesia than with opioids. Analgesia provided by meperidine and tramadol is comparable and approximately 50% of women rated the analgesia as good. Meperidine is better in the second stage than tramadol. Hence in developing nations where availability of facilities is the main limiting factor, intramuscular opioids can be considered suitable alternatives.

Immunonutrition.

Nutrition and immunology are interrelated. Several nutrients like arginine, glutamine, omega-3-fatty acids and nucleotides enhance cellular immunity, modulate tumor cell metabolism and improve clinical outcome in stress situations. Glutamine supplementation has been shown to decrease incidence of sepsis and to reduce length of hospital stay in bone marrow transplant patients, low birth weight infants, surgical and multiple trauma patients. Studies with arginine have shown a reduction in infectious complications and lower mortality, however a better understanding of the biology of arginine is needed. Omega-3-fatty acid supplimentation as in fish oil stimulates the immune system. The beneficial effects of immunonutrition in surgical patients has been demonstrated in several studies. It significantly reduces infectious complications and length of hospital stay. In critically ill patients immunonutrition may decrease infectious complications but it is not associated with a mortality advantage. Pediatric experience is limited, but the future is promising.

Spermicidal & contraceptive properties of Praneem polyherbal pessary.

BACKGROUND & OBJECTIVES: Though a number of barrier methods and potent spermicides are available, most of these have nonoxynol-9 (N-9) as the active ingredient which is observed to cause inflammation and genital ulceration on repeated use. The present study was undertaken to develop a safe spermicide with conjoint microbicidal properties. METHODS: A polyherbal pessary was formulated with purified ingredients from neem (Azadirachta indica) leaves, Sapindus mukerossi (pericarp of fruit) and Mentha citrata oil. Spermicidal action on human sperm was tested by Sander-Cramer slide test in vitro and by post coital tests in vivo. Contraceptive action was tested in rabbits. RESULTS: The combination of the three herbal ingredients resulted in the potentiation of the spermicidal action by 8-folds. The post coital tests confirmed the spermicidal properties of the Praneem polyherbal pessary (PPP) in women with high cervical mucous score around mid estrus. It also prevented in most women the migration of sperm into the cervical mucous. In 15 rabbits studied pregnancy was prevented by the intravaginal administration of PPP, whereas 13 of the 15 animals in the control group became pregnant. INTERPRETATION & CONCLUSION: The Praneem polyherbal pessary has potent spermicidal action on human sperm in vitro and in vivo. When applied in the vagina before mating, it prevented rabbits from becoming pregnant.

Outbreak of Pichia anomala infection in the pediatric service of a tertiary-care center in Northern India.

An outbreak of nosocomial fungemia due to the unusual yeast, Pichia anomala occurred in the pediatric wards of our hospital over a period of 23 months (April 1996 to February 1998). A total of 379 neonates and children (4.2% admissions) were infected. The probable index case was admitted to the pediatric emergency ward, with subsequent transmission to the premature nursery, pediatric intensive care units, and other children wards. Carriage on the hands of health care personnel was likely to be responsible for dissemination of the fungus. The outbreak could only be controlled after a health education campaign to improve hand-washing practices was instituted and after nystatin-fluconazole prophylaxis to all premature neonates and high-risk infants was introduced. In a case-control study, we identified a lower gestational age, a very low birth weight (<1,500 g), and a longer duration of hospital stay as significant risk factors associated with P. anomala fungemia in premature neonates. We conducted a culture prevalence survey of 50 consecutive premature neonates and found that 28% were colonized with P. anomala at a skin or mucosal site on the date of delivery and that 20% of these neonates subsequently developed P. anomala fungemia. We performed multilocus enzyme electrophoresis on 40 P. anomala outbreak isolates (including patient and health care workers' hand isolates), and the results suggested that these isolates were identical. Our study highlights the importance of P. anomala as an emerging nosocomial fungal pathogen.