Statistical heart rate variability analysis for healthy person: Influence of gender and body posture.

Short-term ECG-derived heart rate variability can assess autonomic function non-invasively. The purpose of this study is to investigate the influence of body posture and gender on parasympathetic-sympathetic balance by utilising electrocardiogram (ECG). A total of sixty participants including thirty males (95% CI: 23.34-26.32 years old) and thirty females (95% CI: 23.33-26.07 years old) voluntarily executed three sets of 5-min ECG recordings in supine, sitting and standing posture. A nonparametric Friedman test followed by Bonferroni post-hoc test was carried out to find the statistical differences between the group. A significant difference was observed for RR mean, low frequency (LF), high frequency (HF), ratio LF/HF and the ratio long term variability to short term variability (SD2/SD1) for p < 0.01 while respiration rate (Resp Rate), standard deviation of heart rate (STD_HR), long term variability (SD2), approximate entropy (ApEn), correlation dimension (CD) are non-significant (p > 0.01) for supine, sitting and standing. HRV indices such as standard deviation of NN (SDNN), HRV triangular index (HRVi), and triangular interpolation of NN interval (TINN) are statistically not significant for males but there are significant differences for females at a significance level 1%. Relative reliability and relatedness were evaluated through the interclass coefficient (ICC) and spearman correlation coefficient. The experimental results advocate that there is a posture-specific difference in HRV indices while the correlational studies suggest no such significant differences.

Genetic diversity and population structure of 'Candidatus Liberibacter asiaticus' associated with citrus Huanglongbing in India based on the prophage types.

Huanglongbing (HLB), also known as 'citrus greening', is an extremely destructive disease of citrus worldwide. HLB is associated with three species of the fastidious proteobacterium, Candidatus Liberibacter asiaticus (CaLas), Ca. L. africanus and Ca. L. americanus with CaLas being the most widely distributed around the world and the only species detected and described so far in India, one of the major global citrus fruit producers. Prophages are highly dynamic components in the bacterial genome and play an important role in intraspecies variations. Three types of prophages, Type 1, Type 2 and Type 3 have been identified and described in CaLas so far. In the present study, 441 CaLas isolates sampled across 18 Indian states were used for prophage typing. Based on detection of three prophage types by PCR, all the eight probable combinations of CaLas prophages were identified, including single Type 1 (26.5%), single Type 2 (18.8%), single Type 3 (1.4%), Type 1 + Type 2 (20.4%), Type 1 + Type 3 (12.5%), Type 2 + Type 3 (4.8%), Type 1 + Type 2 + Type 3 (11.3%) and None type (4.3%). Prophage types were confirmed by PCR amplicon sequencing and subsequent phylogenetic analysis. By discovery of all 3 prophages and based on genetic identity and genetic distance, CaLas populations from eighteen citrus growing states were separated into two major Prophage Typing Groups (PTGs): PTG1 and PTG2. The PTG1 comprised of CaLas from North-West India and PTG2 from rest of the country (North-East, Central and South India), and both major groups were further divided into two (PTG1-A, PTG1-B) and three (PTG2-A, PTG2-B and PTG2-C) subgroups respectively. The findings of CaLas population patterns provide evidence for independent origins of HLB-associated CaLas. CRISPR (clustered regularly interspaced short palindromic repeats) array was also detected in CaLas isolates. This is the first report evaluating the genetic variation of a large population of CaLas bacterium in India using the PCR markers from the prophage regions which would certainly assist the ongoing HLB management efforts in India.

Cost-effectiveness of results-based financing, Zambia: a cluster randomized trial.

OBJECTIVE: To evaluate the cost-effectiveness of results-based financing and input-based financing to increase use and quality of maternal and child health services in rural areas of Zambia. METHODS: In a cluster-randomized trial from April 2012 to June 2014, 30 districts were allocated to three groups: results-based financing (increased funding tied to performance on pre-agreed indicators), input-based financing (increased funding not tied to performance) or control (no additional funding), serving populations of 1.33, 1.26 and 1.40 million people, respectively. We assessed incremental financial costs for programme implementation and verification, consumables and supervision. We evaluated coverage and quality effectiveness of maternal and child health services before and after the trial, using data from household and facility surveys, and converted these to quality-adjusted life years (QALYs) gained. FINDINGS: Coverage and quality of care increased significantly more in results-based financing than control districts: difference in differences for coverage were 12.8% for institutional deliveries, 8.2% postnatal care, 19.5% injectable contraceptives, 3.0% intermittent preventive treatment in pregnancy and 6.1% to 29.4% vaccinations. In input-based financing districts, coverage increased significantly more versus the control for institutional deliveries (17.5%) and postnatal care (13.2%). Compared with control districts, 641 more lives were saved (lower-upper bounds: 580-700) in results-based financing districts and 362 lives (lower-upper bounds: 293-430) in input-based financing districts. The corresponding incremental cost-effectiveness ratios were 809 United States dollars (US$) and US$ 413 per QALY gained, respectively. CONCLUSION: Compared with the control, both results-based financing and input-based financing were cost-effective in Zambia.

Does involvement of local NGOs enhance public service delivery? Cautionary evidence from a malaria-prevention program in India.

Partnerships between government and non-state actors that aim to enhance the quality or efficiency of service delivery are increasingly common in today's development policy landscape. We investigate the impacts of such an approach using data from an experimental supportive intervention to India's malaria control program that leveraged local non-state capacity in order to promote mosquito net usage and recommended fever care-seeking patterns. The supportive activities were conducted simultaneously by 3 NGOs, contracted out by the Indian government, in 2 endemic districts in the state of Odisha. We find that program impact significantly varied by location. Examining 3 potential sources of this variation (differential population characteristics, differential health worker characteristics, and differential implementer characteristics), we provide evidence that both population and NGO characteristics significantly affected the success of the program. Specifically, the results suggest that the quality and effort of the local implementer played a key role in the differential effectiveness. We discuss these findings as they relate to the external validity of development policy evaluations and, specifically, for the ability of health and other service delivery systems to benefit from limited non-state capacity in underresourced areas.

Rhodium-catalyzed C-H functionalization of heteroarenes using indoleBX hypervalent iodine reagents.

The C-H indolation of heteroarenes was realized using the benziodoxolone hypervalent iodine reagents indoleBXs. Functionalization of the C-H bond in bipyridinones and quinoline N-oxides catalyzed by a rhodium complex allowed to incorporate indole rings into aza-heteroaromatic compounds. These new transformations displayed complete regioselectivity for the C-6 position of bipyridinones and the C-8 position of quinoline N-oxides and tolerated a broad range of functionalities, such as halogens, ethers, or trifluoromethyl groups.

Cp*CoIII -Catalyzed Bis-isoquinolone Synthesis by C-H Annulation of Arylamide with 1,3-Diyne.

Cp*CoIII -catalyzed highly regioselective mono- and bis-annulation of arylamides with 1,3-diynes using N-OMe as an internal oxidant is demonstrated. This atom-economical transformation does not require any external oxidant and tolerates many functional groups. Various symmetrical and unsymmetrical heterocycles (homo and hetero) are accessed with predictable regio- and chemoselectivity.

Incentives to change: effects of performance-based financing on health workers in Zambia.

BACKGROUND: Performance-based financing (PBF) has been implemented in a number of countries with the aim of transforming health systems and improving maternal and child health. This paper examines the effect of PBF on health workers' job satisfaction, motivation, and attrition in Zambia. It uses a randomized intervention/control design to evaluate before-after changes for three groups: intervention (PBF) group, control 1 (C1; enhanced financing) group, and control 2 (C2; pure control) group. METHODS: Mixed methods are employed. The quantitative portion comprises of a baseline and an endline survey. The survey and sampling scheme were designed to allow for a rigorous impact evaluation of PBF or C1 on several key performance indicators. The qualitative portion seeks to explain the pathways underlying the observed differences through interviews conducted at the beginning and at the three-year mark of the PBF program. RESULTS: Econometric analysis shows that PBF led to increased job satisfaction and decreased attrition on a subset of measures, with little effect on motivation. The C1 group also experienced some positive effects on job satisfaction. The null results of the quantitative assessment of motivation cohere with those of the qualitative assessment, which revealed that workers remain motivated by their dedication to the profession and to provide health care to the community rather than by financial incentives. The qualitative evidence also provides two explanations for higher overall job satisfaction in the C1 than in the PBF group: better working conditions and more effective supervision from the District Medical Office. The PBF group had higher satisfaction with compensation than both control groups because they have higher compensation and financial autonomy, which was intended to be part of the PBF intervention. While PBF could not address all the reasons for attrition, it did lower turnover because those health centers were staffed with qualified personnel and the personnel had role clarity. CONCLUSIONS: In Zambia, the implementation of PBF schemes brought about a significant increase in job satisfaction and a decrease in attrition, but had no significant effect on motivation. Enhanced health financing also increased stated job satisfaction.

Maternal and neonatal service usage and determinants in fragile and conflict-affected situations: a systematic review of Asia and the Middle-East.

BACKGROUND: Fragile and conflict-affected situations (FCS) in Asia and the Middle-East contribute significantly to global maternal and neonatal deaths. This systematic review explored maternal and neonatal health (MNH) services usage and determinants in FCS in Asia and the Middle-East to inform policy on health service provision in these challenging settings. METHODS: This systematic review was conducted using a standardised protocol. Pubmed, Embase, Web of Science, and selected development agency websites were searched for studies meeting inclusion criteria. Studies were assessed for methodological quality using an adapted evaluation tool. Qualitative and quantitative data were synthesized and pooled odds ratios generated for meta-analysis of service-usage determinants. RESULTS: Of 18 eligible peer-reviewed studies, eight were from Nepal, four from Afghanistan, and two each from Iraq, Yemen, and the Palestinian Territories. Fragile situations provide limited evidence on emergency obstetric care, postnatal care, and newborn services. Usage of MNH services was low in all FCS, irrespective of economic growth level. Demand-side determinants of service-usage were transportation, female education, autonomy, health awareness, and ability-to-pay. Supply-side determinants included service availability and quality, existence of community health-workers, costs, and informal payments in health facilities. Evidence is particularly sparse on MNH in acute crises, and remains limited in fragile situations generally. CONCLUSIONS: Findings emphasize that poor MNH status in FCS is a leading contributor to the burden of maternal and neonatal ill-health in Asia and the Middle-East. Essential services for skilled birth attendance and emergency obstetric, newborn, and postnatal care require improvement in FCS. FCS require additional resources and policy attention to address the barriers to appropriate MNH care. Authors discuss the 'targeted policy approach for vulnerable groups' as a means of addressing MNH service usage inequities.

Effect of pay for performance to improve quality of maternal and child care in low- and middle-income countries: a systematic review.

BACKGROUND: Pay for Performance (P4P) mechanisms to health facilities and providers are currently being tested in several low- and middle-income countries (LMIC) to improve maternal and child health (MCH). This paper reviews the existing evidence on the effect of P4P program on quality of MCH care in LMICs. METHODS: A systematic review of literature was conducted according to a registered protocol. MEDLINE, Web of Science, and Embase were searched using the key words maternal care, quality of care, ante natal care, emergency obstetric and neonatal care (EmONC) and child care. Of 4535 records retrieved, only eight papers met the inclusion criteria. Primary outcome of interest was quality of MCH disaggregated into structural quality, process quality and outcomes. Risk of bias across studies was assessed through a customized quality checklist. RESULTS AND DISCUSSION: There were four controlled before after intervention studies, three cluster randomized controlled trials and one case control with post-intervention comparison of P4P programs for MCH care in Burundi, Democratic Republic of Congo, Egypt, the Philippines, and Rwanda. There is some evidence of positive effect of P4P only on process quality of MCH. The effect of P4P on delivery, EmONC, post natal care and under-five child care were not evaluated in these studies. There is weak evidence for P4P's positive effect on maternal and neonatal health outcomes and out-of-pocket expenses. P4P program had a few negative effects on structural quality. CONCLUSION: P4P is effective to improve process quality of ante natal care. However, further research is needed to understand P4P's impact on MCH and their causal pathways in LMICs. TRIAL REGISTRATION: PROSPERO registration number CRD42014013077 .

Strengthening malaria service delivery through supportive supervision and community mobilization in an endemic Indian setting: an evaluation of nested delivery models.

BACKGROUND: Malaria continues to be a prominent global public health challenge. This study tested the effectiveness of two service delivery models for reducing the malaria burden, e.g. supportive supervision of community health workers (CHW) and community mobilization in promoting appropriate health-seeking behaviour for febrile illnesses in Odisha, India. METHODS: The study population comprised 120 villages from two purposively chosen malaria-endemic districts, with 40 villages randomly assigned to each of the two treatment arms, one with both supportive supervision and community mobilization and one with community mobilization alone, as well as an observational control arm. Outcome measures included changes in the utilization of bed nets and timely care-seeking for fever from a trained provider compared to the control group. Analysis was by intention-to-treat. RESULTS: Significant improvements were observed in the reported utilization of bed nets in both intervention arms (84.5% in arm A and 82.4% in arm B versus 78.6% in the control arm; p < 0.001). While overall rates of treatment-seeking were equal across study arms, treatment-seeking from a CHW was higher in both intervention arms (28%; p = 0.005 and 27.6%; p = 0.007) than in the control arm (19.2%). Fever cases were significantly more likely to visit a CHW and receive a timely diagnosis of fever in the combined interventions arm than in the control arm (82.1% vs. 67.1%; p = 0.025). Care-seeking from trained providers also increased with a substitution away from untrained providers. Further, fever cases from the combined interventions arm (60.6%; p = 0.004) and the community mobilization arm (59.3%; p = 0.012) were more likely to have received treatment from a skilled provider within 24 hours than fever cases from the control arm (50.1%). In particular, women from the combined interventions arm were more likely to have received timely treatment from a skilled provider (61.6% vs. 47.2%; p = 0.028). CONCLUSION: A community-based intervention combining the supportive supervision of community health workers with intensive community mobilization and can be effective in improving care-seeking and preventive behaviour and may be used to strengthen the national malaria control programme.

Natural antisense transcripts in Plasmodium falciparum isolates from patients with complicated malaria.

Mechanisms regulating gene expression in malaria parasites are not well understood. Little is known about how the parasite regulates its gene expression during transition from one developmental stage to another and in response to various environmental conditions. Parasites in a diseased host face environments which differ from the static, well adapted in vitro conditions. Parasites thus need to adapt quickly and effectively to these conditions by establishing transcriptional states which are best suited for better survival. With the discovery of natural antisense transcripts (NATs) in this parasite and considering the various proposed mechanisms by which NATs might regulate gene expression, it has been speculated that these might be playing a critical role in gene regulation. We report here the diversity of NATs in this parasite, using isolates taken directly from patients with differing clinical symptoms caused by malaria infection. Using a custom designed strand specific whole genome microarray, a total of 797 NATs targeted against annotated loci have been detected. Out of these, 545 NATs are unique to this study. The majority of NATs were positively correlated with the expression pattern of the sense transcript. However, 96 genes showed a change in sense/antisense ratio on comparison between uncomplicated and complicated disease conditions. The antisense transcripts map to a broad range of biochemical/metabolic pathways, especially pathways pertaining to the central carbon metabolism and stress related pathways. Our data strongly suggests that a large group of NATs detected here are unannotated transcription units antisense to annotated gene models. The results reveal a previously unknown set of NATs that prevails in this parasite, their differential regulation in disease conditions and mapping to functionally well annotated genes. The results detailed here call for studies to deduce the possible mechanism of action of NATs, which would further help in understanding the in vivo pathological adaptations of these parasites.

A prospective study on adult patients of severe malaria caused by Plasmodium falciparum, Plasmodium vivax and mixed infection from Bikaner, northwest India.

BACKGROUND & OBJECTIVES: Description of severe vivax malaria and mixed species infection requires good clinical study. The present study was undertaken to evalute the characteristics of severe malaria patients in Bikaner, northwest India. METHODS: This prospective study included 539 admitted adult patients of severe malaria (Plasmodium falciparum 274, P. vivax 221, and mixed infection of Pv + Pf 44). The diagnosis was confirmed by polymerase chain reaction. The categorization of severe malaria was done strictly as per WHO criteria. RESULTS: The distribution of severe manifestation was similar in severe vivax, falciparum and mixed infections except more cases of thrombocytopenia in P. vivax (p=0.030) and in mixed infection (p=0.004). The risk of developing severe malaria was greatest in patients of mixed infection [53.01% (44/83)] in comparison to Plasmodium falciparum malaria [49.37% (274/555), RR= 1.135; p=0.616] and P. vivax malaria [45.38% (221/ 487), RR = 1.299, p=0.243]. Hepatic dysfunction was the commonest pernicious syndrome [P. falciparum 50% (137/274), P. vivax 43.89% (97/221), and mixed infections 54.55% (24/44)]. Multiorgan dysfunction was present in 40.26% (217/539) patients, the risk was greatest in mixed infection [90.90% (40/44)] in comparison to P. falciparum monoinfection [37.59% (103/274), RR = 12.238; p=0.0001] or P. vivax monoinfection [33.48% (74/ 221), RR = 13.25; p=0.0001]. The risk of mortality in severe malaria was 6.31% (34/539) in which mixed infection had greater risk [9.09% (4/44)] in comparison to P. falciparum [7.30% (20/274); OR = 1.270 (CI 0.347-4.217); p=0.757] or P. vivax [4.52% (10/221); 0R 2.110 (CI 0.527-7.826); p=0.260]. INTERPRETATION & CONCLUSION: Severe vivax or falciparum malaria had almost similar features and prognosis including mortality. Risk of developing severe malaria, multiorgan dysfunction and mortality was more in patients of mixed infection in comparison to P. falciparum or P. vivax monoinfection. A multicentric study on larger number of patients requires further confirmation.

Deep fine-KNN classification of ovarian cancer subtypes using efficientNet-B0 extracted features: a comprehensive analysis.

This study presents a robust approach for the classification of ovarian cancer subtypes through the integration of deep learning and k-nearest neighbor (KNN) methods. The proposed model leverages the powerful feature extraction capabilities of EfficientNet-B0, utilizing its deep features for subsequent fine-grained classification using the fine-KNN approach. The UBC-OCEAN dataset, encompassing histopathological images of five distinct ovarian cancer subtypes, namely, high-grade serous carcinoma (HGSC), clear-cell ovarian carcinoma (CC), endometrioid carcinoma (EC), low-grade serous carcinoma (LGSC), and mucinous carcinoma (MC), served as the foundation for our investigation. With a dataset comprising 725 images, divided into 80% for training and 20% for testing, our model exhibits exceptional performance. Both the validation and testing phases achieved 100% accuracy, underscoring the efficacy of the proposed methodology. In addition, the area under the curve (AUC), a key metric for evaluating the model's discriminative ability, demonstrated high performance across various subtypes, with AUC values of 0.94, 0.78, 0.69, 0.92, and 0.94 for MC. Furthermore, the positive likelihood ratios (LR+) were indicative of the model's diagnostic utility, with notable values for each subtype: CC (27.294), EC (9.441), HGSC (12.588), LGSC (17.942), and MC (17.942). These findings demonstrate the effectiveness of the model in distinguishing between ovarian cancer subtypes, positioning it as a promising tool for diagnostic applications. The demonstrated accuracy, AUC values, and LR+ values underscore the potential of the model as a valuable diagnostic tool, contributing to the advancement of precision medicine in the field of ovarian cancer research.

Community perceptions on malaria and care-seeking practices in endemic Indian settings: policy implications for the malaria control programme.

BACKGROUND: The focus of India's National Malaria Programme witnessed a paradigm shift recently from health facility to community-based approaches. The current thrust is on diagnosing and treating malaria by community health workers and prevention through free provision of long-lasting insecticidal nets. However, appropriate community awareness and practice are inevitable for the effectiveness of such efforts. In this context, the study assessed community perceptions and practice on malaria and similar febrile illnesses. This evidence base is intended to direct the roll-out of the new strategies and improve community acceptance and utilization of services. METHODS: A qualitative study involving 26 focus group discussions and 40 key informant interviews was conducted in two districts of Odisha State in India. The key points of discussion were centred on community perceptions and practice regarding malaria prevention and treatment. Thematic analysis of data was performed. RESULTS: The 272 respondents consisted of 50% females, three-quarter scheduled tribe community and 30% students. A half of them were literates. Malaria was reported to be the most common disease in their settings with multiple modes of transmission by the FGD participants. Adoption of prevention methods was seasonal with perceived mosquito density. The reported use of bed nets was low and the utilization was determined by seasonality, affordability, intoxication and alternate uses of nets. Although respondents were aware of malaria-related symptoms, care-seeking from traditional healers and unqualified providers was prevalent. The respondents expressed lack of trust in the community health workers due to frequent drug stock-outs. The major determinants of health care seeking were socio-cultural beliefs, age, gender, faith in the service provider, proximity, poverty, and perceived effectiveness of available services. CONCLUSION: Apart from the socio-cultural and behavioural factors, the availability of acceptable care can modulate the community perceptions and practices on malaria management. The current community awareness on symptoms of malaria and prevention is fair, yet the prevention and treatment practices are not optimal. Promoting active community involvement and ownership in malaria control and management through strengthening community based organizations would be relevant. Further, timely availability of drugs and commodities at the community level can improve their confidence in the public health system.

Apremilast Adherence and Persistence in Patients with Psoriasis and Psoriatic Arthritis in the Telehealth Setting Versus the In-person Setting During the COVID-19 Pandemic.

INTRODUCTION: Limited access to healthcare during the COVID-19 pandemic prompted patients to seek care using telehealth. In this study, we assessed whether treatment patterns differed for patients with psoriasis (PsO) or psoriatic arthritis (PsA) initiating apremilast by either a telehealth or an in-person visit. METHODS: We estimated adherence and persistence among US patients in the Merative© MarketScan© Commercial and Supplemental Medicare Databases who newly initiated apremilast between April and June 2020, categorized by the type of visit (telehealth or in-person) when apremilast was first prescribed. Adherence was defined as the proportion of days covered (PDC), with PDC ≥ 0.80 considered to indicate high adherence. Persistence was defined as having apremilast available to take without a 60-day gap during follow-up. Factors associated with high adherence and persistence were estimated with logistic and Cox regression. RESULTS: Among apremilast initiators (n = 505), the mean age was 47.6 years, 57.8% were female, and the majority had PsO (79.6%). Telehealth index visits were more likely among patients residing in Northeast USA (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.63-6.71) and Western USA (OR 2.52, 95% CI 1.07-5.93]), those with a prescribing rheumatologist (OR 2.27, 95% CI 1.10-4.68), and those with any baseline telehealth visit (OR 1.91, 85% CI 1.20-3.04). Those initiating apremilast with a telehealth visit (n = 141) had similar mean PDC to those initiating apremilast with an in-person visit (n = 364) (0.695 vs. 0.728; p = 0.272). At the end of the 6-month follow-up, 54.3% of the overall population had high adherence (PDC ≥ 0.80) and 65.1% were persistent. After adjusting for potential confounders, patients initiating apremilast via telehealth had similar full adherence (OR 0.80, 95% CI 0.52-1.21) and persistence as those initiating apremilast in-person. CONCLUSION: Patients with PsO and patients with PsA initiating apremilast via telehealth or in-person during the COVID-19 pandemic had similar medication adherence and persistence during the 6-month follow-up period. These data suggest that patients initiating apremilast can be as effectively managed with telehealth visits as with in-person visits.

Characterization of temperature inducible promoters from a novel rolling circle replicating plasmid of Enterococcus faecium DJ1.

Limited studies have been performed on the characterization of small size plasmids of Enterococcus faecium with the intention of evaluating the strength of their promoters in Escherichia coli. The complete nucleotide sequence (3.825 Kb) and structural organization of E. faecium DJ1 cryptic plasmid pNJAKD is presented. Seven promoter sequences from the pNJAKD plasmid of E. faecium have been identified. The regions coding for the putative promoters were either amplified using PCR based techniques or chemically synthesized as oligonucleotides of different sizes. These were subsequently cloned in the pEGFP vector at the Pvu II site. The efficiency of putative promoter fragments were measured using the intensity of eGFP fluorescence in E. coli JM101, DH5α and BL21(DE3), among which AKD3 exhibited moderate to strongest promoter activity at temperatures of 30, 37, and 42°C.

Thrombocytopenia in childhood malaria with special reference to P. vivax monoinfection: A study from Bikaner (Northwestern India).

Thrombocytopenia is commonly seen in Plasmodium vivax malaria, but its prognostic value has not been addressed in children. This prospective study included 676 admitted children of malaria [Plasmodium falciparum (Pf) monoinfection 262, Plasmodium vivax (Pv) monoinfection 380, and mixed (Pf + Pv) infection 34], in which thrombocytopenia (platelet count <150 × 10(3)/mm(3) on admission) was found in 442 (65.38%) children [Pf monoinfection 55.3% (145/262), Pv monoinfection 73.16% (278/380), and mixed infection 55.88% (19/34)]. The association of thrombocytopenia was statistically significant with Pv monoinfection [73.16% (278/380)] in comparison to either Pf monoinfection [55.34% (145/262); odds ratio (OR) = 2.199 (95% confidence interval (CI) 1.577-3.068), p < 0.0001] or mixed infection [55.88% (19/34); OR = 2.152 (95%CI 1.054-4.394), p = 0.032]. In Pv monoinfection, thrombocytopenia was highest in 0-5 years age group and subsequently decreased with advancing age, whereas in Pf monoinfection it was reverse. Severe thrombocytopenia (platelet count <20 × 10(3)/mm(3)) was present in 16.52% (73/442) children [Pv monoinfection 21.58% (60/278) and Pf monoinfection 8.97% (13/145)]. The risk of developing severe thrombocytopenia was also highest in Pv monoinfection [15.79% (60/380)] in comparison to Pf monoinfection [10.59% (13/262); OR = 3.591 (95%CI 1.928-6.690), p < 0.0001]. Bleeding manifestations were associated in 21.27% (94/442) children [Pf monoinfection 9.92% (26/262), Pv monoinfection 16.58% (63/380), and mixed malaria 14.71% (5/34)]. All the children having bleeding manifestations had thrombocytopenia but low platelet counts were not always associated with abnormal bleeding. The association of severe malaria was significantly more among children having Pv monoinfection with platelet counts <20 × 10(3)/mm(3) [OR = 2.569 (95%CI 1.196-5.517), p < 0.014] with specificity of 88.3% and positive predictive value of 85%. Till today, thrombocytopenia is not included in severe malaria criterion described by WHO, but when platelet counts <20 × 103/mm(3), we advocate it to include as one of the severe malaria criteria.

Novel mutations in the antifolate drug resistance marker genes among Plasmodium vivax isolates exhibiting severe manifestations.

Plasmodium vivax is the predominant species of the human malaria parasite present in the Indian subcontinent. There have been recent reports on Chloroquine (CQ) resistance and severe manifestations shown by P. vivax from different regions of the world including India. This study focuses on Bikaner, India where during the last few years there have been continuous reports of severe manifestations by both Plasmodium falciparum and P. vivax. This region has a widespread use of Chloroquine and Sulfadoxine-Pyrimethamine for the treatment of malaria, but the resistance profiles of these drugs are not available. We report here the profile of mutations in marker genes associated with Chloroquine and antifolate drug resistance among the P. vivax parasites obtained from patients with severe (n=30) and non-severe (n=48) manifestations from this region. Most isolates showed the wild type alleles for both the Chloroquine and antifolate resistance markers (P<0.0005). Except for one isolate showing Y976F mutation in the Pvmdr-1 gene, no reported mutation was observed in the Pvmdr-1 or Pvcrt gene. This is in accordance with the fact that till date no Chloroquine resistance has been reported from this region. However, the single isolate with a mutation in Pvmdr-1 may suggest the beginning of the trend towards decreased susceptibility to Chloroquine. The frequency of PvDHFR-PvDHPS two locus mutations was higher among the patients showing severe manifestations than the patient group with non-severe (uncomplicated) malaria (P<0.003). None of the parasites from patients with uncomplicated P. vivax malaria showed the mutant PvDHPS genotype. Novel mutations in PvDHFR (S117H) and PvDHPS (F365L, D459A and M601I) were observed only in the parasite population obtained from patients exhibiting severe complications. Preliminary homology modeling and molecular docking studies predicted that these mutations apparently do not have any effect on the binding of the drug molecule to the enzyme. However, the presence of novel mutations in the PvDHPS gene indicate a degree of polymorphism of this molecule which is in contrast to available published information.

Unigene-Derived Microsatellite Marker Based Variation Study of Phytophthora nicotianae Isolates Infecting Citrus.

Unigene sequence in public database provides a cost-effective and valuable source, for the development of microsatellite markers also known as unigene-derived microsatellite (UGMS) markers. In our study, genetic variation among 24 Phytophthora nicotianae isolates from five major citrus growing states of India were analysed through UGMS markers. Morphological and clustering results indicated variation among these Phytophthora nicotianae were independent of its geographical confinement and showed 62.27% polymorphism. The study also validated the potential use of UGMS markers.

Palladium-Catalyzed trans-Hydroalkoxylation: Counterintuitive Use of an Aryl Iodide Additive to Promote C-H Bond Formation.

We report an enantioselective palladium-catalyzed trans-hydroalkoxylation of propargylic amines with a trifluoroacetaldehyde-derived tether to build chiral oxazolidines. Diastereoselective hydrogenation using a heterogeneous palladium catalyst then gave access to protected benzylic amino alcohols in 45-87% yields and 84-94% ee values. Hydroalkoxylation of the alkynes required a catalytic amount of aryl iodide, highlighting the counterintuitive key role played by a putative Pd(II)/ArI oxidative addition complex to promote oxypalladation/protodemetalation.