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.

Megakaryocytes Enhance Mesenchymal Stromal Cells Proliferation and Inhibit Differentiation.

Megakaryocytes (MKs) can induce proliferation of calvarial osteoblasts [Ciovacco et al., 2009], but this same phenomenon has not been reported for bone marrow stromal populations from long bones. Bone marrow contains several types of progenitor cells which can be induced to differentiate into multiple cell types. Herein, we examined mesenchymal stromal cell proliferation and osteoblastic differentiation when rabbit or mouse MK were cultured with i) rabbit bone marrow stromal cells, ii) rabbit dental pulp stromal cells, or iii) mouse bone marrow stromal cells. Our results demonstrated that rabbit and mouse stromal cells co-cultured with rabbit MK or mouse MK, have significant increases in proliferation on day 7 by 52%, 46%, and 24%, respectively, compared to cultures without MK. Conversely, alkaline phosphatase (ALP) activity was lower at various time points in these cells when cultures contain MK. Similarly, calcium deposition observed at day 14 rabbit bone marrow and dental pulp stromal cells and day 21 mouse bone marrow stromal cells was 63%, 69%, and 30% lower respectively, when co-cultured with MK. Gene expression studies reveal transcriptional changes broadly consistent with increased proliferation and decreased differentiation. Transcript levels of c-fos (associated with cell proliferation) trended higher after 3, 7, and 14 days in culture. Also, expression of alkaline phosphatase, osteonectin, osterix, and osteopontin, which are markers for osteoblast differentiation, showed MK-induced decreases in a cell type and time dependent manner. Taken together, these data suggest that MK play a role in stromal cell proliferation and differentiation, from multiple sites/locations in multiple species. This article is protected by copyright. All rights reserved.

Detection of the aadA1 and aac (3)-1V resistance genes in Acinetobacter baumannii.

Acinetobacter baumannii is a gram-negative aerobic bacterium that can be found in different environments, such as food, containing vegetables, meat, and fish; moreover, it can be present in soil and freshwater. A. baumannii has globally considered an opportunistic nosocomial bacterium in the healthcare setting contributing to increased morbidity and mortality. The current study aimed to detect the aminoglycoside genes in A. baumannii isolated from different clinical causes. In total, 20 isolates of A. baumannii were obtained from different clinical cases. Bacterial isolate DNA was extracted using a DNA extraction kit. Quantus Fluorometer was used to detect the concentration of the extracted DNA in order to detect the goodness of samples. 1 µl of DNA and 199 µl of diluted QuantiFlour Dye were mixed. After 5 min incubation at room temperature, DNA concentration values were evaluated, and following the initial amplification of the A. baumannii aadA1 gene, 20 µl of PCR product with F and R primers were sent to Sanger sequencing. The results of the antimicrobial susceptibility revealed that A. baumannii isolates were resistant to Gentamicin (95%), Amikacin (90%), and Tobramycin (60%). Molecular investigation of the aadA1 and aac (3)-IV genes exhibited that the aadA1 gene was detected in 15% of the isolates. However, the aac (3)-IV gene was not detected in any of the isolates. The gel electrophoresis revealed that the molecular weight of the aadA1 gene was 490bp. The DNA sequence of the aadA1 gene was conducted in this study, and the results exhibited no mutations in all isolates.

Residual Bacteriome after Chemomechanical Preparation of Root Canals in Primary and Secondary Infections.

INTRODUCTION: Secondary infections may be linked to the presence of residual microorganisms within dental root canals. The purpose of this study was to investigate the bacterial composition of primary and secondary root canal infections before and after chemomechanical treatment. METHODS: Samples were collected before chemomechanical preparation (S1) and before obturation (S2) from 19 subjects (10 primary and 9 secondary infections). DNA was extracted, and the V3/V4 region of the 16S ribosomal RNA gene was amplified using the 347 F/803R primers and paired-end sequenced using the MiSeq (Illumina, San Diego, CA) instrument. RESULTS: Sequencing analysis yielded partial 16S ribosomal RNA gene sequences that were taxonomically classified into 10 phyla and 143 genera. The most prevalent phyla in the S1 and S2 samples were Firmicutes and Bacteroides; however, when comparing between sample groups, Proteobacteria seem to have been enriched in secondary infections. The dominant genera in the primary S1 samples were Bacillus, Streptococcus, and Prevotella, whereas Bacillus, Streptococcus, and Selenomonas dominated the secondary infection S1 samples. Bacillus and Marinilactibacillus were the most dominant genera in the primary and secondary S2 samples. The mean number of operational taxonomic units per sample was 32,656 (±12,124 SD) and 37,113 (±16,994 SD) in the S1 and S2 samples, respectively. Alpha and beta diversities presented the same pattern within samples from both groups. CONCLUSIONS: Great interindividual variations in the bacterial composition of the root canal biofilms were observed. There was no difference in the bacterial composition before and after treatment, although some genera survived and seem to be part of a residual microbiome. Our findings revealed a high diversity of the bacterial communities present in root canal infections after chemomechanical treatment, although the majority of the taxa detected were in low abundance.

Effect of Vitamin D supplementation in patients with liver cirrhosis having spontaneous bacterial peritonitis: a randomized controlled study.

OBJECTIVE: Spontaneous Bacterial Peritonitis (SBP) is one of the most serious liver cirrhosis with ascites complications. Vitamin D (Vit D) deficiency has been associated with a high risk of infection and mortality in cirrhotic patients. Herein, the assessment of Vit D level as a prognostic marker in SBP patients and the impact of Vit D supplementation on their treatment plan was studied as well. PATIENTS AND METHODS: Ascetic patients with SBP and Vit D deficiency were divided randomly into treatment and control groups. The control group received standard treatment without Vit D and the treatment group received standard treatment plus Vit D. Clinical monitoring of Vit D was done over 6 months. RESULTS: At baseline, all patients in both groups revealed an elevated serum and ascetic TLC, AST, ALT, total and direct bilirubin, in addition to elevation in INR and procalcitonin (PCT) level. Univariate regression analysis confirmed that deficiency of Vit D was an independent predictor of infection and mortality (p < 0.01; Crude Hazard Ratio: 0.951). Over 6 months, the study revealed significant improvement in serum Vit D level in the treatment group (34.6 ± 9.2 and 18.3 ± 10.0 ng/mL; p < 0.001). Moreover, a statistically significant increase in survival rate (64% vs. 42%; p < 0.05) and duration (199.5 days vs. 185.5 days; p < 0.05) were recorded as well. Univariate and multivariate regression analysis confirmed that Vit D supplementation was positively correlated to survival over 6 months (p < 0.001; Adjusted Hazard Ratio: 0.895). CONCLUSIONS: Vit D deficiency is prevalent in SBP cirrhotic patients and is used as an independent predictor of infection and death. Therefore, Vit D supplementation revealed improvement in their response to treatment.

Anti-idiotype-mediated epitope spreading and diminished phagocytosis by a human monoclonal antibody recognizing late-stage apoptotic cells.

Apoptotic cells are considered an important auto-antigenic source in diseases such as systemic lupus erythematosus (SLE). A human monoclonal antibody demonstrating exquisite specificity towards late-stage apoptotic cells was generated from an SLE patient. Polyreactive recognition of ribonucleoproteins Ro52 and Ro60 was observed. The antibody significantly diminished the phagocytosis of apoptotic cells and a concomitant decrease in transforming growth factor-beta (TGF-beta) secretion was observed. Light and heavy chain sequencing revealed the antibody to be in essentially germline configuration. Elicited anti-idiotypic antibodies bound distinct self-antigens and showed augmented reactivity towards apoptotic cells as well. Thus, near-germline encoded antibodies recognizing antigens externalized during the process of apoptosis can mediate a variety of potentially pathogenic effects; decreases in the phagocytic uptake of dying cells would constitute a disease-perpetuating event and stimulation of the idiotypic network could lead to intermolecular epitope spreading, increasing the range of molecular targets..

Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder caused by an opportunistic fungal pathogen, Aspergillus fumigatus (AFU:). Lung surfactant proteins SP-A and SP-D can interact with the glycosylated antigens and allergens of AFU:, inhibit specific IgE binding to these allergens, and block histamine release from sensitized basophils. We have now examined the therapeutic effect of exogenous administration of human SP-A, SP-D, and a recombinant fragment of SP-D (rSP-D), in a murine model of pulmonary hypersensitivity induced by AFU: antigens and allergens, which resembles human ABPA immunologically. The ABPA mice exhibited high levels of AFU:-specific IgG and IgE, blood eosinophilia, extensive infiltration of lymphocytes and eosinophils in the lung sections, and a Th2 cytokine response. Treatment with SP-A, SP-D, and rSP-D lowered blood eosinophilia, pulmonary infiltration, and specific Ab levels considerably, which persisted up to 4 days in the SP-A-treated ABPA mice, and up to 16 days in the SP-D- or rSP-D-treated ABPA mice. The levels of IL-2, IL-4, and IL-5 were decreased, while the level of IFN-gamma was raised in the splenic supernatants of the treated mice, indicating a marked shift from Th2 to Th1 response. These results clearly implicate pulmonary SP-A and SP-D in the modulation of allergic reactions.

Cardiovascular disease risk factors in 2 distinct ethnic groups: Indian and Pakistani compared with American premenopausal women.

BACKGROUND: Although people from the Indian subcontinent have high rates of cardiovascular disease (CVD), studies of such in Indian and Pakistani women living in the United States are lacking. OBJECTIVE: This study accounted for variability in serum lipid (total cholesterol and triacylglycerol) and lipoprotein [LDL cholesterol, lipoprotein(a), and HDL cholesterol] concentrations in Indian and Pakistani compared with American premenopausal women in the United States. Body composition, regional fat distribution, dietary intake, and energy expenditure were compared between groups. DESIGN: The 2 groups were 47 Indian and Pakistani and 47 American women. Health was assessed via medical history, physical activity, body composition (via anthropometry and dual-energy X-ray absorptiometry), dietary intake (via 7-d food records), and serum lipids. RESULTS: Serum total cholesterol, triacylglycerol, LDL cholesterol, lipoprotein(a), the ratio of total to HDL cholesterol, and the ratio of LDL to HDL cholesterol were greater (P <0.03), whereas HDL-cholesterol values were lower (P = 0.011) in Indians and Pakistanis than in Americans. Multiple regression analysis indicated that approximately 18% of the variance in total cholesterol (P = 0.0010) and LDL cholesterol (P = 0.0009) was accounted for by ethnicity, energy expenditure, and the ratio of the sum of central to the sum of peripheral skinfold thicknesses. Ethnicity, sum of central skinfold thicknesses, ratio of polyunsaturated to saturated fat, and monounsaturated fat intake accounted for approximately 43% of the variance in triacylglycerol concentration (P < 0.0001). Monounsaturated fat, percentage body fat, and alcohol intake accounted for approximately 26% of variance in HDL cholesterol. Ethnicity contributed approximately 22% of the 25% overall variance in lipoprotein(a). CONCLUSIONS: Results suggest that these Indian and Pakistani women are at higher CVD risk than their American counterparts, but that increasing their physical activity is likely to decrease overall and regional adiposity, thereby improving their serum lipid profiles.

Hypoglycaemic, hypolipidemic and antioxidant properties of tulsi (Ocimum sanctum linn) on streptozotocin induced diabetes in rats.

Effect of oral administration of 200 mg/Kg body weight of the aqueous extract ofOcimum sanctum (Tulsi) mixed with diet for eight weeks to diabetic (streptozotocin induced) rats was studied. There was significant reduction in fasting blood glucose, serum lipid profile, lipid peroxidation products, (LPO) and improvement in glucose tolerance. The aqueous extract also decreased LPO formation (thiobarbituric acid reactive substances TBARS) and increased antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione transferase (GT) and one antioxidant reduced glutathione (GSH) in plasma and rat liver, lung, kidney and brain. The decrease in TBARS and increase in GSH, SOD, CAT, GPX, and GT clearly shows the antioxidant property ofOcimum sanctum.

A cohort study of psychosurgery cases from a defined population.

All cases from an urban population treated by psychosurgery over a 20 year period were followed up; 44 out of 47 were available for study, and 33 of these were interviewed. Outcome was measured on a five-point scale, and follow-up was from 1 to 20 years, with a mean of 11; almost all patients previously had had severe, disabling and intractable illnesses. Operations were non-stereotactic (36), stereotactic (6), with double procedures in one case: outcome was better in the non-stereotactic group. On a five-point scale of outcome, 25 of the 33 interviewed patients were placed in the two best categories, as were eight patients of the 11 who were assessed by case records. Adverse effects were reported in 14 cases, but most were not serious. Only one death could definitely be related to operation. Depression, agoraphobia, obsessional neurosis, and certain aspects of schizophrenia all responded well in the majority of cases. Leucotomy should remain available as a treatment of last resort for some intractable psychiatric disorders.

Protective role of lung surfactant protein D in a murine model of invasive pulmonary aspergillosis.

The protective effects of intranasal administration of amphotericin B (AmB), human SP-A, SP-D and a 60-kDa fragment of SP-D (rSP-D) were examined in a murine model of invasive pulmonary aspergillosis (IPA). The untreated group of IPA mice showed no survival at 7 days postinfection. Treatment with AmB, SP-D, and rSP-D increased the survival rate to 80, 60, and 80%, respectively, suggesting that SP-D (and rSP-D) can protect immunosuppressed mice from an otherwise fatal challenge with Aspergillus fumigatus conidia.

Chemical composition and potential health effects of prunes: a functional food?

Prunes are dried plums, fruits of Prunus domestica L., cultivated and propagated since ancient times. Most dried prunes are produced from cultivar d'Agen, especially in California and France, where the cultivar originated. After harvest, prune-making plums are dehydrated in hot air at 85 to 90 degrees C for 18 h, then further processed into prune juice, puree, or other prune products. This extensive literature review summarizes the current knowledge of chemical composition of prunes and their biological effects on human health. Because of their sweet flavor and well-known mild laxative effect, prunes are considered to be an epitome of functional foods, but the understanding of their mode of action is still unclear. Dried prunes contain approximately 6.1 g of dietary fiber per 100 g, while prune juice is devoid of fiber due to filtration before bottling. The laxative action of both prune and prune juice could be explained by their high sorbitol content (14.7 and 6.1 g/100 g, respectively). Prunes are good source of energy in the form of simple sugars, but do not mediate a rapid rise in blood sugar concentration, possibly because of high fiber, fructose, and sorbitol content. Prunes contain large amounts of phenolic compounds (184 mg/100 g), mainly as neochlorogenic and chlorogenic acids, which may aid in the laxative action and delay glucose absorption. Phenolic compounds in prunes had been found to inhibit human LDL oxidation in vitro, and thus might serve as preventive agents against chronic diseases, such as heart disease and cancer. Additionally, high potassium content of prunes (745 mg/100 g) might be beneficial for cardiovascular health. Dried prunes are an important source of boron, which is postulated to play a role in prevention of osteoporosis. A serving of prunes (100 g) fulfills the daily requirement for boron (2 to 3 mg). More research is needed to assess the levels of carotenoids and other phytochemicals present in prunes to ensure correct labeling and accuracy of food composition tables in order to support dietary recommendations or health claims.

Correlation of pseudohypoxemia and leukocytosis in chronic lymphocytic leukemia.

Pseudohypoxemia has been reported in leukemic patients with extreme leukocytosis, and it is characterized by a low oxygen saturation on arterial blood gas analysis despite normal saturation on pulse oximetry. We report the case of a 51-year-old man with chronic lymphocytic leukemia and an elevated white blood cell (WBC) count after splenectomy, his progressive postoperative pseudohypoxemia gradually improved as the leukocytosis was lowered by chemotherapy. We believe this is the first report to show a statistically significant correlation between the WBC count and the degree of pseudohypoxemia in a patient with leukemia.

Lifestyle and biologic contributors to proximal femur bone mineral density and hip axis length in two distinct ethnic groups of premenopausal women.

Although relatively little is known about osteoporotic risk factors in women from the Indian subcontinent, osteoporotic fractures usually occur 10-20 years earlier in Indian men and women compared with their western Caucasian counterparts. The primary purpose of this cross-sectional study was to determine the relative contributions of ethnicity, reproductive history, body size (height, weight) and composition, bone turnover, serum 25(OH)vitamin D(3) [25(OH)D(3)], dietary intake (of calcium, fiber and alcohol) and energy expenditure to femoral bone mineral density (BMD) in Indian and Pakistani (Indian/Pakistani; n = 47) versus American (n = 47) Caucasians. We also contrasted femoral BMD and hip axis length in these two distinct groups of premenopausal females living in the USA. The Indian/Pakistani (0.875 +/- 0.096) women had lower (p = 0.0014) femoral BMD (g/cm(2)) than their American (0.937 +/- 0.088) counterparts, placing them at greater osteoporotic risk. However, the shorter (p = 0.0002) hip axis length (cm) of the Indian/Pakistani (10.54 +/- 0.57) versus American (11.11 +/- 0.78) Caucasians might attenuate hip fracture risk in the former group. Significant contributors to proximal femur BMD were maximum non-pregnant lifetime weight, age at menarche, ratio of summation sigma central-to-peripheral skinfold thicknesses, calcium intake from milk and usual alcohol intake. Although serum 25(OH)D(3) and urinary N-telopeptide concentrations did not contribute to femoral BMD in the regression models, the lower (p<0.0001) serum 25(OH)D(3) (33.1 +/- 16.5 vs 64.0 +/- 22.0 nmol/l) and higher (p = 0.0004) urinary N-telopeptide (45.9 +/- 43.3 vs 18.9 +/- 18.7 nmol BCE/mmol) values in Indian/Pakistani versus American Caucasians, respectively, coupled with their lower BMD, places the Indian/Pakistani women at greater osteoporotic risk. These results suggest that a clinical trial to increase BMD and reduce osteoporotic risk is warranted in this ethnic group of premenopausal women.

Breast cancer risk factors in two distinct ethnic groups: Indian and Pakistani vs. American premenopausal women.

Asian Indians from the Indian subcontinent have low rates of breast cancer, but studies on breast cancer risk factors in Indian and Pakistani women living in the United States are lacking. This study contrasted breast cancer risk factors [serum total 17 beta-estradiol (E2), sex hormone-binding globulin-bound E2, available E2, estrone (E1), and dehydroepiandrosterone sulfate, reproductive history, family history of cancer, body composition/size, dietary intake, physical activity, and excretion of isoflavones] between two distinct ethnic groups of premenopausal women residing in the United States. We also determined the contribution of these and other factors to the variability of each sex hormone. Distributions of values for serum total E2, available E2, and sex hormone-binding globulin-bound E2 (%) were greater (p < 0.005) in American (n = 47) than in Indian and Pakistani (n = 47) women. Multiple regression analysis indicated that 26% of the variability (p < or = 0.0001) in serum E2 was accounted for by the ratio of total cholesterol to high-density-lipoprotein cholesterol, length of time in the United States, and saturated fat intake, whereas less (17%) variability was accounted for by available E2 (representing free E2 + albumin-bound E2), contributed by the ratio of total cholesterol to high-density-lipoprotein cholesterol and saturated fat intake. Five variables accounted for 31% of the variability (p < or = 0.0001) in E1. The major finding of this study was that circulating sex hormone concentrations were determined more by environmental factors than by ethnicity, which was not a significant contributor to any of the serum hormones.