Substantial and sustained reduction in under-5 mortality, diarrhea, and pneumonia in Oshikhandass, Pakistan: evidence from two longitudinal cohort studies 15 years apart.

BACKGROUND: Oshikhandass is a rural village in northern Pakistan where a 1989-1991 verbal autopsy study showed that diarrhea and pneumonia were the top causes of under-5 mortality. Intensive surveillance, active community health education and child health interventions were delivered in 1989-1996; here we assess improvements in under-5 mortality, diarrhea, and pneumonia over this period and 15 years later. METHODS: Two prospective open-cohort studies in Oshikhandass from 1989 to 1996 (Study 1) and 2011-2014 (Study 2) enrolled all children under age 60 months. Study staff trained using WHO guidelines, conducted weekly household surveillance and promoted knowledge on causes and management of diarrhea and pneumonia. Information about household characteristics and socioeconomic status was collected. Hurdle models were constructed to examine putative risk factors for diarrhea and pneumonia. RESULTS: Against a backdrop of considerable change in the socioeconomic status of the community, under-5 mortality, which declined over the course of Study 1 (from 114.3 to 79.5 deaths/1000 live births (LB) between 1989 and 1996), exceeded Sustainable Development Goal 3 by Study 2 (19.8 deaths/ 1000 LB). Reductions in diarrhea prevalence (20.3 to 2.2 days/ Child Year [CY]), incidence (2.1 to 0.5 episodes/ CY), and number of bloody diarrhea episodes (18.6 to 5.2%) seen during Study 1, were sustained in Study 2. Pneumonia incidence was 0.5 episodes /CY in Study 1 and 0.2/CY in Study 2; only 5% of episodes were categorized as severe or very severe in both studies. While no individual factors predicted a statistically significant difference in diarrhea or pneumonia episodes, the combined effect of water, toilet and housing materials was associated with a significant decrease in diarrhea; higher household income was the most protective factor for pneumonia in Study 1. CONCLUSIONS: We report a 4-fold decrease in overall childhood mortality, and a 2-fold decrease in childhood morbidity from diarrhea and pneumonia in a remote rural village in Pakistan between 1989 and 2014. We conclude that significant, sustainable improvements in child health may be achieved through improved socioeconomic status and promoting interactions between locally engaged health workers and the community, but that continued efforts are needed to improve health worker training, supervision, and the rational use of medications. TRIAL REGISTRATION: Not Applicable.

Prevalence of female genital tuberculosis, its risk factors and associated clinical features among the women of Andaman Islands, India: a community-based study.

OBJECTIVE: There is scarcity of information on the prevalence of female genital tuberculosis (FGTB) in the community. The present study was carried out to estimate the prevalence of FGTB, its risk factors and associated clinical features. STUDY DESIGN: Community-based cross-sectional survey. METHODS: This study was carried during October 2011 and May 2014 in the Andaman Islands. A total of 13,300 women aged 20-59 years were primarily screened using a structured questionnaire. About 721 (5.4%) were found initially eligible for screening for genital tuberculosis by clinical examination and specimen collection for laboratory tests but only 460 (63.8%) expressed their willingness. Endometrial specimens were collected from 405 (88%) subjects. The association of the potential risk factors with genital tuberculosis was tested by Chi-squared test. A similar analysis was performed to identify clinical features associated with genital tuberculosis. RESULTS: The estimated prevalence of FGTB was 45.1 cases per 100,000 women (95% confidence interval [CI]: 16.6-98.1). Infertility and oligomenorrhoea were identified as clinical features associated with FGTB. Past history of tuberculosis and history of close contact with tuberculosis cases were identified as risk factors. CONCLUSIONS: This study shows the prevalence of FGTB among the female population of the Andaman Islands. Though the estimated prevalence was close to the expected prevalence, but as only 63.8% of the eligible women could be adequately screened, a much higher prevalence of FGTB could not be ruled out. Infertility, oligomenorrhoea, past history of tuberculosis and contact with tuberculosis case were identified as factors associated with genital tuberculosis.

LC-MS Guided Isolation of Bioactive Principles from Iris hookeriana and Bioevaluation of Isolates for Antimicrobial and Antioxidant Activities.

The genus Iris is diverse both in the abundance of secondary metabolities as well as the biological activities. The rhizomes of Iris hookeriana exhibit significant anthelminthic activity against gastrointestinal nematodes of sheep. Although Iris hookeriana has been a subject of the study of so many phytochemical studies, yet we report some constituents for the first time from this plant using a different isolation approach. This manuscript presents the isolation, antimicrobial and antioxidant evaluation of bioactive principles from Iris hookeriana. LC-MS guided isolation technique was applied for the separation of target constituents. The isolates were characterised by spectral techniques and subjected to antioxidant evaluation by DPPH assay. Four compounds; resveratrol, resveratroloside, junipeginin C and isorhamnetin-3-O-neohesperidoside were isolated for the first time along with 3 known compounds viz piceid, irigenin and iridin from I. hookeriana using this approach. The antioxidant activity screening of the isolates revealed that all the 4 constituents isolated for the first time, have strong antioxidant potential with IC50 of 14.0 µg/ml (resveratroloside), 19.7 µg/ml (junipeginen C), 12.8 µg/ml (resveratrol) and 19.8 µg/ml (isorhamnetin-3-O-neohesperodoside). So it can be safely concluded that LC-MS guided isolation of chemical compounds from Iris hookeriana has furnished 4 antioxidant constituents. Thus Iris hookeriana can act as as a good source of wonder molecule resveratrol and its 2 glycosides, resveratrolside and piceid which upon hydrolysis can be converted into the parent drug resveratrol.

Diurnally subperiodic filariasis in India-prospects of elimination: precept to action?

The elimination of lymphatic filariasis in the Andaman and Nicobar Islands provides unique opportunities and challenges at the same time. Since these islands are remote, are sparsely populated, and have poor transport networks, mass drug administration programs are likely to be difficult to implement. Diurnally subperiodic Wuchereria bancrofti vectored by Downsiomyia nivea was considered for the scope of vector control options. Considering the bioecology of this mosquito, vector control including personal protection measures may not be feasible. However, since these islands are covered by separate administrative machinery which also plays an important role in regulating the food supply, the use of diethylcarbamazine (DEC)-fortified salt as a tool for the interruption of transmission is appealing. DEC-fortified salt has been successfully pilot tested in India and elsewhere, operationally used by China for eliminating lymphatic filariasis. Administration of DEC-fortified salt though simple, rapid, safe, and cost-effective, challenges are to be tackled for translating this precept into action by evolving operationally feasible strategy. Although the use of DEC-fortified salt is conceptually simple, it requires commitment of all sections of the society, an elaborate distribution mechanism that ensures the use of DEC-fortified salt only in the endemic communities, and a vigorous monitoring mechanism. Here, we examine the inbuilt administrative mechanisms to serve the tribal people, health infrastructure, and public distribution system and discuss the prospects of putting in place an operationally feasible strategy for its elimination.

Management of malaria threat following tsunami in Andaman & Nicobar Islands, India and impact of altered environment created by tsunami on malaria situation of the islands.

Andaman & Nicobar Islands (Indian Territory) are situated in the Bay of Bengal and endemic for malaria with perennial transmission. Anopheles sundaicus which prefers to breed in brackish water, is known as the main vector for malaria and maintains high endemicity of malaria. Tsunami waves entered the inhabited coastal areas, caused heavy devastation and left large areas inundated causing exceptionally high breeding sources for vector mosquitoes of malaria. The disaster created a new habitat suitable for the proliferation of malaria and other disease-carrying mosquitoes besides making thousands of people homeless. They were living in temporary open shelters, getting more exposed to mosquito bites. The population already had existing high parasite load. Hence, there was a real threat of malaria outbreak in the area. However, malaria was effectively controlled due to strategic planning and timely remedial measures. Malaria situation was monitored closely and epidemiological data of three subsequent years from 2005 to 2007 after tsunami were analysed and compared with pre-tsunami malaria data from 1986 to 2004. In this paper, effect of tsunami on malaria profile in these islands has been discussed along with action taken for its control.

[The role of perineal ultrasound compared to lateral cysturethrogram in urogynecological evaluations]. / Die Perinealsonographie im Vergleich zum lateralen Zysturethrogramm bei der Inkontinenzdiagnostik der Frau.

PURPOSE: The aim of this study was to evaluate prospectively whether perineal ultrasound is comparable to the lateral cysturethrogram in the evaluation of incontinent women. PATIENTS AND METHODS: Following urodynamic investigations, a lateral cysturethrogram and perineal ultrasound (5 MHz probe, bladder filling 300 mL) were performed in 98 incontinent women. In women with detrusor overactivity and consecutively reduced bladder capacity, ultrasound was performed at maximum capacity. To evaluate differences between perineal ultrasound and the cysturethrogram, the difference between bladder neck and lower border of symphysis and the retrovesicle angle beta were determined at rest and during the Valsalva manoeuvre. RESULTS: Using perineal ultrasound, the differences between bladder neck and symphysis could be determined at rest and during the Valsalva manoeuvre in all patients. The determination of the retrovesical angle beta was possible in all patients at rest and in 89 of the 98 women during the Valsalva manoeuvre. The lateral cysturethrogram enabled the determination of difference between bladder neck and symphysis and the retrovesicle angle beta at rest in 81 of 98 women. During the Valsalva manoeuvre, the difference between bladder neck and symphysis and retrovesicle angle beta could be determined in 72 of the 98 women. In the 26 remaining women, the determination was impossible due to severe adiposity or cystoceles of the second or third degree. CONCLUSIONS: Perineal ultrasound provides comparable data to the lateral cysturethrogram. In patients with adiposity, perineal ultrasound seems to be superior. Within the routine evaluation of women suffering from incontinence, the lateral cysturethrogram can be replaced by perineal ultrasound without any limitations of the diagnostic value.

Intravesical foreign body: case report.

Foreign bodies of the urinary bladder may occur by self insertion or migration from the neighbouring organs. All the foreign bodies when left for long act as a nidus for calculus formation. The patient usually presents with dysuria, intermittent urinary tract infection or suprapubic pain. Here we report two cases of vesical foreign body which was removed by the cystoscopy.

Case report. Successful outcome of invasive nasal sinus zygomycosis in a child with relapsed acute lymphoblastic leukaemia due to liposomal amphotericin B.

We report a case of life-threatening nasal sinus zygomycosis that developed during remission induction therapy for a relapsed acute lymphoblastic leukaemia. The patient was successfully treated with liposomal amphotericin B and granulocyte-colony stimulating factor followed by surgical reconstruction of the resultant cutaneous defect.

Tannin contents and protein digestibility of black grams (Vigna mungo) after soaking and cooking.

The objective of this research was to ascertain the effects of soaking black grams (Cultivar AARI-5732) in different salt solutions at different temperatures and different time periods, and different methods of cooking on the tannin content and protein digestibility. Tannin content of black grams was reduced to various extents by soaking at 30 degrees and 100 degrees C for different time periods. However, soaking at 100 degrees C increased the rate of extraction and reduced the extraction time of tannins. Soaking black grams in water at 100 degrees C reduced tannins by 22.14% in 45 minutes whereas about 2.5 times more tannin was reduced after soaking in sodium bicarbonate solution with or without sodium chloride. Maximum improvement in protein digestibility was also observed after soaking black grams in sodium bicarbonate solution. Tannin contents were further reduced along with improvement in protein digestibility as a result of cooking.

Metabolic regulation of Na(+)/P(i)-cotransporter-1 gene expression in H4IIE cells.

We showed that the rat Na(+)/P(i) cotransporter-1 (RNaPi-1) gene was regulated by insulin and glucose in rat hepatocytes. The aim of this work was to elucidate signaling pathways of insulin-mediated metabolic regulation of the RNaPi-1 gene in H4IIE cells. Insulin increased RNaPi-1 mRNA abundance in the presence of glucose and decreased RNaPi-1 mRNA in the absence of glucose, clearly establishing an involvement of metabolic signals for insulin-induced upregulation of the RNaPi-1 gene. Pyruvate and insulin increased RNaPi-1 expression but downregulated L-pyruvate kinase, indicating the existence of gene-specific metabolic signals. Although fructose, glycerol, and lactate could support insulin-induced upregulation of the RNaPi-1 gene, compounds entering metabolism beyond pyruvate oxidation, such as acetate and citrate, could not, suggesting that RNaPi-1-specific metabolic signals are generated at or above pyruvate oxidation. Wortmannin, LY-294002, and rapamycin abolished the insulin effect on the RNaPi-1 gene, whereas expression of dominant negative Asn(17) Ras and mitogen-activating protein kinase (MAPK) kinase (MEK) inhibitor PD-98059 exhibited no effect. Thus we herein propose that metabolic regulation of RNaPi-1 expression by insulin is mediated through the phosphatidylinositol 3-kinase/p70 ribosomal S6 kinase pathways, but not the Ras/MAPK pathway.

Biochemical changes in wheat during storage at three temperatures.

Biochemical changes in wheat grains stored at 10, 25 and 45 degrees C for six months were studied. A significant decrease in pH and an increase in titratable acidity was observed during storage of wheat grains at 25 degrees C and 45 degrees C. Moisture contents of wheat grains decreased by 15% at 25 degrees C and 26% at 45 degrees C during six months of storage. A significant decrease in water soluble amylose (20-28%) along with an increase in insoluble amylose contents (7.6-17%) were observed during storage at 25 and 45 degrees C. Amylase activity of the samples showed a decrease as the storage progressed. Total soluble sugars increased by 9% at 10 degrees C and 12% at 25 degrees C; a 37% decrease was observed after six months storage at 45 degrees C. Total available lysine decreased by 18.0% and 22.6% at 25 and 45 degrees C, respectively, after six months storage. In vitro protein digestibility of wheat grains decreased by 5.00% at 25 degrees C and 10.28% at 45 degrees C during six months of storage. However, no significant biochemical changes occurred during storage at 10 degrees C.

Binding of EBNA-1 to DNA creates a protease-resistant domain that encompasses the DNA recognition and dimerization functions.

The Epstein-Barr virus nuclear antigen EBNA-1 is essential for replication of the viral DNA during latency. EBNA-1 binds as a dimer to palindromic recognition sequences within the plasmid origin of replication, ori-P. In this study, proteinase K susceptibility has been used to further characterize the DNA-binding domain of EBNA-1. Limited protease digestion of EBNA-1 (amino acids 408 to 641) generated a smaller DNA-binding species that had a degree of inherent protease resistance. When EBNA-1 was preincubated with a specific DNA probe, the protease resistance of the smaller binding species increased 100-fold, suggesting that the conformation of EBNA-1 changes on binding. The protease-resistant species comprised an 18-kDa polypeptide that was further cleaved at high levels of protease to 11- and 5.4-kDa products. A model of the proposed protease-resistant domain structure is presented. Constructions carrying serial, internal deletions across the 18-kDa domain were created. Each of the deletions perturbed dimerization ability and abolished DNA binding. These studies suggest that the DNA-binding and dimerization motifs of EBNA-1 lie within a conformationally discrete domain whose overall integrity is necessary for EBNA-1-DNA interaction.

Definition of the sequence requirements for binding of the EBNA-1 protein to its palindromic target sites in Epstein-Barr virus DNA.

Interaction between the trans-acting DNA-binding protein EBNA-1 and cis-acting sequences in the ori-P region of Epstein-Barr virus DNA is required for maintenance of the viral plasmid state in latently infected B cells and is involved in the regulation of transcription during latency. In the Epstein-Barr virus genome, a total of 26 EBNA-1-binding sites occur within three clustered loci referred to as the family of repeats and dyad symmetry locus of ori-P and the separate BamHI-Q locus. Incubation of a bacterially expressed carboxy-terminal domain of EBNA-1 (28,000-molecular-weight EBNA-1 [28K EBNA-1]) with synthetic monomer and dimer consensus binding sites gave characteristic DNA-protein complexes in a mobility retardation assay. A similar approach with the naturally occurring Q locus confirmed that it contains two distinct but low-affinity binding sites. We then examined the precise sequence requirements for EBNA-1 binding, using a set of 30-base-pair oligonucleotides designed to contain symmetric point mutations within both halves of the palindromic target site. Analysis of all possible single substitutions between positions 1 and 10 in the consensus half-palindrome sequence revealed that positions 9 and 10 did not contribute to EBNA-1 binding and that considerable flexibility could be tolerated at positions 1 and 2. Positions 3 through 8 of the recognition site had the most stringent requirements, with transversions at these positions either reducing or eliminating binding. The relative spacing of the halves of the palindrome was also critical, since the addition or removal of 2 base pairs at the center of the sequence abolished binding. Similar results were obtained when a partially purified preparation of intact Raji EBNA-1 was substituted for the 28K EBNA-1, and the results were further supported by methylation interference studies which indicated contact points between EBNA-1 and the guanine residues at positions -8, -7, and +3 of the binding site. The three naturally occurring EBNA-1-binding loci have previously been shown to differ in their relative affinities for EBNA-1. The present study indicates that the sequence variations occurring within the family of repeats would not affect binding affinity, whereas certain base substitutions within the Q and dyad symmetry sites would be predicted to contribute to the observed lower affinities of these sites. An apparent Kd of 1.5 x 10(-11) M for binding of 28K EBNA-1 to a consensus recognition site was calculated from Scatchard analysis.

A study of 123 new born infants.

This paper is based on a study of 123 new born infants selected from general wards, private nursing homes. It was found that the average weight of babies born to mothers of upper social class was more than that of middle and lower social class. The chest and head circumference of upper social class was greater than the middle and lower social class, but there was no difference in their length. It was interesting to note that the incidence of prematurity was much higher in the middle and lower social class and was the incidence of congenital anomalies.