36 results on '"Lalji S"'
Search Results
2. Y chromosomal noncoding RNAs regulate autosomal gene expression via piRNAs in mouse testis
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Hemakumar M. Reddy, Rupa Bhattacharya, Shrish Tiwari, Kankadeb Mishra, Pranatharthi Annapurna, Zeenath Jehan, Nissankararao Mary Praveena, Jomini Liza Alex, Vishnu M. Dhople, Lalji Singh, Mahadevan Sivaramakrishnan, Anurag Chaturvedi, Nandini Rangaraj, Thomas Michael Shiju, Badanapuram Sreedevi, Sachin Kumar, Ram Reddy Dereddi, Sunayana M. Rayabandla, and Rachel A. Jesudasan
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Mouse Y chromosome ,Long noncoding RNA ,Alternative splicing ,piRNA ,Pirmy ,Pirmy-like RNAs ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Deciphering the functions of Y chromosome in mammals has been slow owing to the presence of repeats. Some of these repeats transcribe coding RNAs, the roles of which have been studied. Functions of the noncoding transcripts from Y chromosomal repeats however, remain unclear. While a majority of the genes expressed during spermatogenesis are autosomal, mice with different deletions of the long arm of the Y chromosome (Yq) were previously also shown to be characterized by subfertility, sterility and sperm abnormalities, suggesting the presence of effectors of spermatogenesis at this location. Here we report a set of novel noncoding RNAs from mouse Yq and explore their connection to some of the autosomal genes expressed in testis. Results We describe a set of novel mouse male-specific Y long arm (MSYq)-derived long noncoding (lnc) transcripts, named Pirmy and Pirmy-like RNAs. Pirmy shows a large number of splice variants in testis. We also identified Pirmy-like RNAs present in multiple copies at different loci on mouse Y chromosome. Further, we identified eight differentially expressed autosome-encoded sperm proteins in a mutant mouse strain, XYRIIIqdel (2/3 Yq-deleted). Pirmy and Pirmy-like RNAs have homology to 5′/3′UTRs of these deregulated autosomal genes. Several lines of experiments show that these short homologous stretches correspond to piRNAs. Thus, Pirmy and Pirmy-like RNAs act as templates for several piRNAs. In vitro functional assays reveal putative roles for these piRNAs in regulating autosomal genes. Conclusions Our study elucidates a set of autosomal genes that are potentially regulated by MSYq-derived piRNAs in mouse testis. Sperm phenotypes from the Yq-deleted mice seem to be similar to that reported in inter-specific male-sterile hybrids. Taken together, this study provides novel insights into possible role of MSYq-derived ncRNAs in male sterility and speciation.
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- 2021
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3. De novo 7p partial trisomy characterized by subtelomeric FISH and whole-genome array in a girl with mental retardation
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Saranya G, Aswini S, N. Chandra, Lalji S, Kanakavalli M Kulashekaran, Venkata O Padmalatha, Lakshmi Rao Kandukuri, Jagan Singh Meena, Turlapati Raseswari, and Durgadatta T
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Genetics ,Biochemistry, medical ,medicine.medical_specialty ,lcsh:QH426-470 ,Research ,Biochemistry (medical) ,Cytogenetics ,Chromosome ,Chromosomal rearrangement ,Biology ,medicine.disease ,Subtelomere ,Biochemistry ,Human genetics ,Telomere ,lcsh:Genetics ,Chromosome 19 ,medicine ,Molecular Medicine ,Genetics(clinical) ,Trisomy ,Molecular Biology ,Genetics (clinical) - Abstract
Chromosome rearrangements involving telomeres have been established as one of the major causes of idiopathic mental retardation/developmental delay. This case of 7p partial trisomy syndrome in a 3-year-old female child presenting with developmental delay emphasizes the clinical relevance of cytogenetic diagnosis in the better management of genetic disorders. Application of subtelomeric FISH technique revealed the presence of interstitial telomeres and led to the ascertainment of partial trisomy for the distal 7p segment localized on the telomeric end of the short arm of chromosome 19. Whole-genome cytogenetic microarray-based analysis showed a mosaic 3.5 Mb gain at Xq21.1 besides the approximately 24.5 Mb gain corresponding to 7p15.3- > pter. The possible mechanisms of origin of the chromosomal rearrangement and the clinical relevance of trisomy for the genes lying in the critical regions are discussed.
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- 2011
4. P04.19: Vena previa: prenatal sonographic diagnosis of a variant of vasa previa
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Pugash, D., primary, Lalji, S., additional, and Lim, K., additional
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- 2005
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5. OC18.03: Just images: Isolated multiple large umbilical cord cysts and thick prominent Wharton's jelly
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Abdullah, S., primary, Yong, S. L., additional, Lopez, E., additional, Lalji, S., additional, and Pugash, D., additional
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- 2005
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6. Identification and management of young infants with possible serious bacterial infection where referral was not feasible in rural Lucknow district of Uttar Pradesh, India: An implementation research.
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Shally Awasthi, Naveen Kesarwani, Raj Kumar Verma, Girdhar Gopal Agarwal, Luxmi Shanker Tewari, Ravi Krishna Mishra, Lalji Shukla, Arun Kumar Raut, Shamim Ahmad Qazi, Samira Aboubaker, Yasir Bin Nisar, Rajiv Bahl, and Monika Agarwal
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Medicine ,Science - Abstract
BACKGROUND:Based on World Health Organization guidelines, Government of India recommended management of possible serious bacterial infection (PSBI) in young infants up to two months of age on an outpatient basis where referral is not feasible. We implemented the guideline in program setting to increase access to treatment with high treatment success and low resultant mortality. METHODS:Implementation research was conducted in four rural blocks of Lucknow district in Uttar Pradesh, India. It included policy dialogues with the central and state government and district level officials. A Technical Support Unit was established. Thereafter, capacity building across all cadres of health workers in the implementation area was done for strengthening of home based newborn care (HBNC) program, skills enhancement for identification and management of PSBI, logistics management to ensure availability of necessary supplies, monitoring and evaluation as well as providing feedback. Data was collected by the research team. RESULTS:From June 2017 to February 2019 there were 24,448 live births in a population of 856106. We identified 1302 infants, aged 0-59 days, with any sign of PSBI leading to a coverage of 53% (1302/2445), assuming an incidence of 10%. However, in the establishment phase the coverage was 33%, while it was 85% in the implementation phase. Accredited social health activists (ASHAs) identified 81.2% (1058/1302) cases while rest were identified by families. ASHAs increased home visits within first 7 days of life in home based newborn care program from 74.3% (2781/3738) to 89.0% (3128/3513) and detection of cases of PSBI from 1.6% (45/2781) to 8.7% (275/3128) in the first and last quarter of the project, respectively. Of these 18.7% (244/1302) refused referral to government health system and 6.7% (88/1302) were treated in a hospital. Among cases of PSBI, there were 13.3% (173/1302) cases of fast breathing in young infant aged 7-59 days in whom referral was not needed. Of these 147 were treated by oral amoxicillin and 95.2% (140/147) were cured. Among those who needed referral, simplified treatment was given when referral was refused. There were 2.9% (37/1302) cases of fast breathing at ages of 0-6 days of which 34 were treated by simplified treatment with100% (34/34) cured;66.5% (866/1302) were cases of clinical severe infection of which 685 treated by simplified treatment with94.2% (645/685)cured and 09 died;17.3% (226/1302) cases of critical illness of which 93 were treated by simplified treatment, as a last resort, 72% (67/93) cured and 16 died. Among 255 cases who either did not seek formal treatment or sought it at private facilities, 96 died. CONCLUSION:Simplified treatment for PSBI is feasible in public program settings in northern India with good cure rates. It required system strengthening and supportive supervision.
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- 2020
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7. 'Like sugar in milk': reconstructing the genetic history of the Parsi population
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Gyaneshwer Chaubey, Qasim Ayub, Niraj Rai, Satya Prakash, Veena Mushrif-Tripathy, Massimo Mezzavilla, Ajai Kumar Pathak, Rakesh Tamang, Sadaf Firasat, Maere Reidla, Monika Karmin, Deepa Selvi Rani, Alla G. Reddy, Jüri Parik, Ene Metspalu, Siiri Rootsi, Kurush Dalal, Shagufta Khaliq, Syed Qasim Mehdi, Lalji Singh, Mait Metspalu, Toomas Kivisild, Chris Tyler-Smith, Richard Villems, and Kumarasamy Thangaraj
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Parsi ,Zoroastrian ,autosomes ,mtDNA ,Y chromosome ,ancient DNA ,Biology (General) ,QH301-705.5 ,Genetics ,QH426-470 - Abstract
Abstract Background The Parsis are one of the smallest religious communities in the world. To understand the population structure and demographic history of this group in detail, we analyzed Indian and Pakistani Parsi populations using high-resolution genetic variation data on autosomal and uniparental loci (Y-chromosomal and mitochondrial DNA). Additionally, we also assayed mitochondrial DNA polymorphisms among ancient Parsi DNA samples excavated from Sanjan, in present day Gujarat, the place of their original settlement in India. Results Among present-day populations, the Parsis are genetically closest to Iranian and the Caucasus populations rather than their South Asian neighbors. They also share the highest number of haplotypes with present-day Iranians and we estimate that the admixture of the Parsis with Indian populations occurred ~1,200 years ago. Enriched homozygosity in the Parsi reflects their recent isolation and inbreeding. We also observed 48% South-Asian-specific mitochondrial lineages among the ancient samples, which might have resulted from the assimilation of local females during the initial settlement. Finally, we show that Parsis are genetically closer to Neolithic Iranians than to modern Iranians, who have witnessed a more recent wave of admixture from the Near East. Conclusions Our results are consistent with the historically-recorded migration of the Parsi populations to South Asia in the 7th century and in agreement with their assimilation into the Indian sub-continent's population and cultural milieu "like sugar in milk". Moreover, in a wider context our results support a major demographic transition in West Asia due to the Islamic conquest.
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- 2017
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8. The light skin allele of SLC24A5 in South Asians and Europeans shares identity by descent.
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Chandana Basu Mallick, Florin Mircea Iliescu, Märt Möls, Sarah Hill, Rakesh Tamang, Gyaneshwer Chaubey, Rie Goto, Simon Y W Ho, Irene Gallego Romero, Federica Crivellaro, Georgi Hudjashov, Niraj Rai, Mait Metspalu, C G Nicholas Mascie-Taylor, Ramasamy Pitchappan, Lalji Singh, Marta Mirazon-Lahr, Kumarasamy Thangaraj, Richard Villems, and Toomas Kivisild
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Genetics ,QH426-470 - Abstract
Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22-28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India.
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- 2013
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9. Genetic structure of Tibeto-Burman populations of Bangladesh: evaluating the gene flow along the sides of Bay-of-Bengal.
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Nurun Nahar Gazi, Rakesh Tamang, Vipin Kumar Singh, Ahmed Ferdous, Ajai Kumar Pathak, Mugdha Singh, Sharath Anugula, Pandichelvam Veeraiah, Subburaj Kadarkaraisamy, Brijesh Kumar Yadav, Alla G Reddy, Deepa Selvi Rani, Syed Saleheen Qadri, Lalji Singh, Gyaneshwer Chaubey, and Kumarasamy Thangaraj
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Medicine ,Science - Abstract
Human settlement and migrations along sides of Bay-of-Bengal have played a vital role in shaping the genetic landscape of Bangladesh, Eastern India and Southeast Asia. Bangladesh and Northeast India form the vital land bridge between the South and Southeast Asia. To reconstruct the population history of this region and to see whether this diverse region geographically acted as a corridor or barrier for human interaction between South Asia and Southeast Asia, we, for the first time analyzed high resolution uniparental (mtDNA and Y chromosome) and biparental autosomal genetic markers among aboriginal Bangladesh tribes currently speaking Tibeto-Burman language. All the three studied populations; Chakma, Marma and Tripura from Bangladesh showed strikingly high homogeneity among themselves and strong affinities to Northeast Indian Tibeto-Burman groups. However, they show substantially higher molecular diversity than Northeast Indian populations. Unlike Austroasiatic (Munda) speakers of India, we observed equal role of both males and females in shaping the Tibeto-Burman expansion in Southern Asia. Moreover, it is noteworthy that in admixture proportion, TB populations of Bangladesh carry substantially higher mainland Indian ancestry component than Northeast Indian Tibeto-Burmans. Largely similar expansion ages of two major paternal haplogroups (O2a and O3a3c), suggested that they arose before the differentiation of any language group and approximately at the same time. Contrary to the scenario proposed for colonization of Northeast India as male founder effect that occurred within the past 4,000 years, we suggest a significantly deep colonization of this region. Overall, our extensive analysis revealed that the population history of South Asian Tibeto-Burman speakers is more complex than it was suggested before.
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- 2013
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10. Genetic affinities of the central Indian tribal populations.
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Gunjan Sharma, Rakesh Tamang, Ruchira Chaudhary, Vipin Kumar Singh, Anish M Shah, Sharath Anugula, Deepa Selvi Rani, Alla G Reddy, Muthukrishnan Eaaswarkhanth, Gyaneshwer Chaubey, Lalji Singh, and Kumarasamy Thangaraj
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Medicine ,Science - Abstract
BackgroundThe central Indian state Madhya Pradesh is often called as 'heart of India' and has always been an important region functioning as a trinexus belt for three major language families (Indo-European, Dravidian and Austroasiatic). There are less detailed genetic studies on the populations inhabited in this region. Therefore, this study is an attempt for extensive characterization of genetic ancestries of three tribal populations, namely; Bharia, Bhil and Sahariya, inhabiting this region using haploid and diploid DNA markers.Methodology/principal findingsMitochondrial DNA analysis showed high diversity, including some of the older sublineages of M haplogroup and prominent R lineages in all the three tribes. Y-chromosomal biallelic markers revealed high frequency of Austroasiatic-specific M95-O2a haplogroup in Bharia and Sahariya, M82-H1a in Bhil and M17-R1a in Bhil and Sahariya. The results obtained by haploid as well as diploid genetic markers revealed strong genetic affinity of Bharia (a Dravidian speaking tribe) with the Austroasiatic (Munda) group. The gene flow from Austroasiatic group is further confirmed by their Y-STRs haplotype sharing analysis, where we determined their founder haplotype from the North Munda speaking tribe, while, autosomal analysis was largely in concordant with the haploid DNA results.Conclusions/significanceBhil exhibited largely Indo-European specific ancestry, while Sahariya and Bharia showed admixed genetic package of Indo-European and Austroasiatic populations. Hence, in a landscape like India, linguistic label doesn't unequivocally follow the genetic footprints.
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- 2012
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11. The phylogeography of Y-chromosome haplogroup h1a1a-m82 reveals the likely Indian origin of the European Romani populations.
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Niraj Rai, Gyaneshwer Chaubey, Rakesh Tamang, Ajai Kumar Pathak, Vipin Kumar Singh, Monika Karmin, Manvendra Singh, Deepa Selvi Rani, Sharath Anugula, Brijesh Kumar Yadav, Ashish Singh, Ramkumar Srinivasagan, Anita Yadav, Manju Kashyap, Sapna Narvariya, Alla G Reddy, George van Driem, Peter A Underhill, Richard Villems, Toomas Kivisild, Lalji Singh, and Kumarasamy Thangaraj
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Medicine ,Science - Abstract
Linguistic and genetic studies on Roma populations inhabited in Europe have unequivocally traced these populations to the Indian subcontinent. However, the exact parental population group and time of the out-of-India dispersal have remained disputed. In the absence of archaeological records and with only scanty historical documentation of the Roma, comparative linguistic studies were the first to identify their Indian origin. Recently, molecular studies on the basis of disease-causing mutations and haploid DNA markers (i.e. mtDNA and Y-chromosome) supported the linguistic view. The presence of Indian-specific Y-chromosome haplogroup H1a1a-M82 and mtDNA haplogroups M5a1, M18 and M35b among Roma has corroborated that their South Asian origins and later admixture with Near Eastern and European populations. However, previous studies have left unanswered questions about the exact parental population groups in South Asia. Here we present a detailed phylogeographical study of Y-chromosomal haplogroup H1a1a-M82 in a data set of more than 10,000 global samples to discern a more precise ancestral source of European Romani populations. The phylogeographical patterns and diversity estimates indicate an early origin of this haplogroup in the Indian subcontinent and its further expansion to other regions. Tellingly, the short tandem repeat (STR) based network of H1a1a-M82 lineages displayed the closest connection of Romani haplotypes with the traditional scheduled caste and scheduled tribe population groups of northwestern India.
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- 2012
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12. Unique Case Reports Associated with Ovarian Failure: Necessity of Two Intact X Chromosomes
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Lakshmi Rao Kandukuri, Venkata Padmalatha, Murthy Kanakavalli, Raseswari Turlapati, Mangalipally Swapna, Metuku Vidyadhari, Govindaraghavan Saranaya, Kattera Himaja, Mamata Deenadayal, Bipin Kumar Sethi, Prasun Deb, Nalini Gupta, Baidyanath Chakraborthy, Pratibha Nallari, and Lalji Singh
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Genetics ,QH426-470 - Abstract
Premature ovarian failure is defined as the loss of functional follicles below the age of 40 years and the incidence of this abnormality is 0.1% among the 30–40 years age group. Unexplained POF is clinically recognized as amenorrhoea (>6 months) with low level of oestrogen and raised level of Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH > 20 IU/l) occurring before the age of 40. It has been studied earlier that chromosomal defects can impair ovarian development and its function. Since there is paucity of data on chromosomal defects in Indian women, an attempt is made to carry out cytogenetic evaluation in patients with ovarian failure. Cytogenetic analysis of women with ovarian defects revealed the chromosome abnormalities to be associated with 14% of the cases analyzed. Interestingly, majority of the abnormalities involved the X-chromosome and we report two unique abnormalities, (46,XXdel(Xq21-22) and q28) and (mos,45XO/46,X+ringX) involving X chromosome in association with ovarian failure. This study revealed novel X chromosome abnormalities associated with ovarian defects and these observations would be helpful in genetic counseling and apart from, infertility clinics using the information to decide suitable strategies to help such patients.
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- 2012
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13. IL-4 haplotype -590T, -34T and intron-3 VNTR R2 is associated with reduced malaria risk among ancestral indian tribal populations.
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Aditya Nath Jha, Vipin Kumar Singh, Namrata Kumari, Ashish Singh, Justin Antony, Hoang van Tong, Sakshi Singh, Sudhanshu S Pati, Pradeep K Patra, Rajender Singh, Nguyen L Toan, Le H Song, Amal Assaf, Iara J T Messias-Reason, Thirumalaisamy P Velavan, Lalji Singh, and Kumarasamy Thangaraj
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Medicine ,Science - Abstract
BACKGROUND: Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between T(H)1 and T(H)2 immune response, immunoglobulin class switching and humoral immunity. Polymorphisms in this gene have been reported to affect the risk of infectious and autoimmune diseases. METHODS: We have analyzed three regulatory IL-4 polymorphisms; -590C>T, -34C>T and 70 bp intron-3 VNTR, in 4216 individuals; including: (1) 430 ethnically matched case-control groups (173 severe malaria, 101 mild malaria and 156 asymptomatic); (2) 3452 individuals from 76 linguistically and geographically distinct endogamous populations of India, and (3) 334 individuals with different ancestry from outside India (84 Brazilian, 104 Syrian, and 146 Vietnamese). RESULTS: The -590T, -34T and intron-3 VNTR R2 alleles were found to be associated with reduced malaria risk (PT and -34C>T, and P = 0.003 for VNTR). These three alleles were in strong LD (r²>0.75) and the TTR2 (-590T, -34T and intron-3 VNTR R2) haplotype appeared to be a susceptibility factor for malaria (P = 0.009, OR = 0.552, 95% CI = 0.356 -0.854). Allele and genotype frequencies differ significantly between caste, nomadic, tribe and ancestral tribal populations (ATP). The distribution of protective haplotype TTR2 was found to be significant (χ²₃ = 182.95, p-value
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- 2012
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14. Role of androgen receptor CAG repeat polymorphism and X-inactivation in the manifestation of recurrent spontaneous abortions in Indian women.
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Meka Aruna, Shilpi Dasgupta, Pisapati V S Sirisha, Sadaranga Andal Bhaskar, Surapaneni Tarakeswari, Lalji Singh, and B Mohan Reddy
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Medicine ,Science - Abstract
The aim of the present study was to investigate the role of CAG repeat polymorphism and X-chromosome Inactivation (XCI) pattern in Recurrent Spontaneous Abortions among Indian women which has not been hitherto explored. 117 RSA cases and 224 Controls were included in the study. Cases were recruited from two different hospitals--Lakshmi Fertility Clinic, Nellore and Fernandez Maternity Hospital, Hyderabad. Controls were roughly matched for age, ethnicity and socioeconomic status. The CAG repeats of the Androgen Receptor gene were genotyped using a PCR-based assay and were analysed using the GeneMapper software to determine the CAG repeat length. XCI analysis was also carried out to assess the inactivation percentages. RSA cases had a significantly greater frequency of allele sizes in the polymorphic range above 19 repeats (p = 0.006), which is the median value of the controls, and in the biallelic mean range above 21 repeats (p = 0.002). We found no evidence of abnormal incidence of skewed X-inactivation. We conclude that longer CAG repeat lengths are associated with increased odds for RSA with statistical power estimated to be ∼90%.
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- 2011
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15. The influence of natural barriers in shaping the genetic structure of Maharashtra populations.
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Kumarasamy Thangaraj, B Prathap Naidu, Federica Crivellaro, Rakesh Tamang, Shashank Upadhyay, Varun Kumar Sharma, Alla G Reddy, S R Walimbe, Gyaneshwer Chaubey, Toomas Kivisild, and Lalji Singh
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Medicine ,Science - Abstract
BackgroundThe geographical position of Maharashtra state makes it rather essential to study the dispersal of modern humans in South Asia. Several hypotheses have been proposed to explain the cultural, linguistic and geographical affinity of the populations living in Maharashtra state with other South Asian populations. The genetic origin of populations living in this state is poorly understood and hitherto been described at low molecular resolution level.Methodology/principal findingsTo address this issue, we have analyzed the mitochondrial DNA (mtDNA) of 185 individuals and NRY (non-recombining region of Y chromosome) of 98 individuals belonging to two major tribal populations of Maharashtra, and compared their molecular variations with that of 54 South Asian contemporary populations of adjacent states. Inter and intra population comparisons reveal that the maternal gene pool of Maharashtra state populations is composed of mainly South Asian haplogroups with traces of east and west Eurasian haplogroups, while the paternal haplogroups comprise the South Asian as well as signature of near eastern specific haplogroup J2a.Conclusions/significanceOur analysis suggests that Indian populations, including Maharashtra state, are largely derived from Paleolithic ancient settlers; however, a more recent (∼10 Ky older) detectable paternal gene flow from west Asia is well reflected in the present study. These findings reveal movement of populations to Maharashtra through the western coast rather than mainland where Western Ghats-Vindhya Mountains and Narmada-Tapti rivers might have acted as a natural barrier. Comparing the Maharastrian populations with other South Asian populations reveals that they have a closer affinity with the South Indian than with the Central Indian populations.
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- 2010
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16. Role of progesterone receptor polymorphisms in the recurrent spontaneous abortions: Indian case.
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Meka Aruna, Theeya Nagaraja, Sadaranga Andal, Surapaneni Tarakeswari, Pisapati V S Sirisha, Alla G Reddy, Kumarasamy Thangaraj, Lalji Singh, and B Mohan Reddy
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Medicine ,Science - Abstract
BACKGROUND: We attempt to ascertain if the 3 linked single nucleotide polymorphisms (SNPs) of the Progesterone Receptor (PR) gene (exon 1: G 1031 C; S344T, exon 4: G 1978 T; L660V and exon 5: C 2310 T; H770H) and the PROGINS insertion in the intron G, between exons 7 and 8, are associated with Recurrent Spontaneous Abortion (RSA) in the Indian population. METHODOLOGY/PRINCIPAL FINDINGS: A total of 143 women with RSA and 150 controls were sequenced for all the 8 exons looking for the above 3 linked SNPs of the PR gene earlier implicated in the RSA, as well as for any new SNPs that may be possibly found in the Indian population. PROGINS insertion was screened by electrophoresis. We did not find any new mutations, not observed earlier, in our population. Further, we did not find significant role of the *2 allele (representing the mutant allele at the three SNP loci) or the T2 allele (PROGINS insertion) in the manifestation of RSA. We also did not find an LD pattern between each of the 3 SNPs and the PROGINS insertion. CONCLUSIONS/SIGNIFICANCE: The results suggest that the PR gene mutations may not play any exclusive role in the manifestation of RSA, and instead, given significantly higher frequency of the *2 allele among the normal women, we surmise if it does not really confer a protective role among the Indian populations, albeit further studies are required in the heterogeneous populations of this region before making any conclusive statement.
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- 2010
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17. Deep rooting in-situ expansion of mtDNA Haplogroup R8 in South Asia.
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Kumarasamy Thangaraj, Amrita Nandan, Vishwas Sharma, Varun Kumar Sharma, Muthukrishnan Eaaswarkhanth, Pradeep Kumar Patra, Sandhya Singh, Sashi Rekha, Monika Dua, Narendra Verma, Alla G Reddy, and Lalji Singh
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Medicine ,Science - Abstract
BackgroundThe phylogeny of the indigenous Indian-specific mitochondrial DNA (mtDNA) haplogroups have been determined and refined in previous reports. Similar to mtDNA superhaplogroups M and N, a profusion of reports are also available for superhaplogroup R. However, there is a dearth of information on South Asian subhaplogroups in particular, including R8. Therefore, we ought to access the genealogy and pre-historic expansion of haplogroup R8 which is considered one of the autochthonous lineages of South Asia.Methodology/principal findingsUpon screening the mtDNA of 5,836 individuals belonging to 104 distinct ethnic populations of the Indian subcontinent, we found 54 individuals with the HVS-I motif that defines the R8 haplogroup. Complete mtDNA sequencing of these 54 individuals revealed two deep-rooted subclades: R8a and R8b. Furthermore, these subclades split into several fine subclades. An isofrequency contour map detected the highest frequency of R8 in the state of Orissa. Spearman's rank correlation analysis suggests significant correlation of R8 occurrence with geography.Conclusions/significanceThe coalescent age of newly-characterized subclades of R8, R8a (15.4+/-7.2 Kya) and R8b (25.7+/-10.2 Kya) indicates that the initial maternal colonization of this haplogroup occurred during the middle and upper Paleolithic period, roughly around 40 to 45 Kya. These results signify that the southern part of Orissa currently inhabited by Munda speakers is likely the origin of these autochthonous maternal deep-rooted haplogroups. Our high-resolution study on the genesis of R8 haplogroup provides ample evidence of its deep-rooted ancestry among the Orissa (Austro-Asiatic) tribes.
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- 2009
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18. Austro-Asiatic tribes of Northeast India provide hitherto missing genetic link between South and Southeast Asia.
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B Mohan Reddy, B T Langstieh, Vikrant Kumar, T Nagaraja, A N S Reddy, Aruna Meka, A G Reddy, K Thangaraj, and Lalji Singh
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Medicine ,Science - Abstract
Northeast India, the only region which currently forms a land bridge between the Indian subcontinent and Southeast Asia, has been proposed as an important corridor for the initial peopling of East Asia. Given that the Austro-Asiatic linguistic family is considered to be the oldest and spoken by certain tribes in India, Northeast India and entire Southeast Asia, we expect that populations of this family from Northeast India should provide the signatures of genetic link between Indian and Southeast Asian populations. In order to test this hypothesis, we analyzed mtDNA and Y-Chromosome SNP and STR data of the eight groups of the Austro-Asiatic Khasi from Northeast India and the neighboring Garo and compared with that of other relevant Asian populations. The results suggest that the Austro-Asiatic Khasi tribes of Northeast India represent a genetic continuity between the populations of South and Southeast Asia, thereby advocating that northeast India could have been a major corridor for the movement of populations from India to East/Southeast Asia.
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- 2007
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19. Correction: Global Patterns in Human Mitochondrial DNA and Y-Chromosome Variation Caused by Spatial Instability of the Local Cultural Processes.
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Vikrant Kumar, Banrida T Langstieh, Komal V Madhavi, Vegi M Naidu, Hardeep Pal Singh, Silpak Biswas, Kumarasamy Thangaraj, Lalji Singh, and B. Mohan Reddy
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Genetics ,QH426-470 - Published
- 2006
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20. Global patterns in human mitochondrial DNA and Y-chromosome variation caused by spatial instability of the local cultural processes.
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Vikrant Kumar, Banrida T Langstieh, Komal V Madhavi, Vegi M Naidu, Hardeep Pal Singh, Silpak Biswas, Kumarasamy Thangaraj, Lalji Singh, and B Mohan Reddy
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Genetics ,QH426-470 - Abstract
Because of the widespread phenomenon of patrilocality, it is hypothesized that Y-chromosome variants tend to be more localized geographically than those of mitochondrial DNA (mtDNA). Empirical evidence confirmatory to this hypothesis was subsequently provided among certain patrilocal and matrilocal groups of Thailand, which conforms to the isolation by distance mode of gene diffusion. However, we expect intuitively that the patterns of genetic variability may not be consistent with the above hypothesis among populations with different social norms governing the institution of marriage, particularly among those that adhere to strict endogamy rules. We test the universality of this hypothesis by analyzing Y-chromosome and mtDNA data in three different sets of Indian populations that follow endogamy rules to varying degrees. Our analysis of the Indian patrilocal and the matrilocal groups is not confirmatory to the sex-specific variation observed among the tribes of Thailand. Our results indicate spatial instability of the impact of different cultural processes on the genetic variability, resulting in the lack of universality of the hypothesized pattern of greater Y-chromosome variation when compared to that of mtDNA among the patrilocal populations.
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- 2006
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21. In Vivo Identification, Survival, and Functional Efficacy of Transplanted Hepatocytes in Acute Liver Failure Mice Model by Fish Using Y-Chromosome Probe
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Donkena Krishna Vanaja, Bhattiprolu Sivakumar, Rachel A. Jesudasan, Lalji Singh, Marasanapalle Kalle Janardanasarma, and Chittoor Mohammed Habibullah
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Medicine - Abstract
Hepatocyte transplantation has excited much interest in lending temporary metabolic support to a failing liver following acute liver injury. The exact site from which they act and the clinical, biochemical, and histological changes in the recipient body following hepatocyte transplantation is yet to be worked out. The present study is an attempt to delineate location and function of transplanted hepatocytes and also the overall survival of these cells with a fluorescent in situ hybridization (FISH) technique using a Y-chromosome–specific probe in a carbon tetrachloride (CCl 4 )-induced mice model of fulminant hepatic failure. Fifty-five syngenic adult Swiss female mice of approximately the same age and body weight were divided into three groups. Group-1 (n = 15), which received mineral oil, served as a negative control. Group-II (n = 15) received CCl 4 (3 mL/kg) 40% vol/vol in mineral oil, by gavage served as positive control for hepatic failure. Group-III (n = 25) received intrasplenic transplantation of syngenic single cell suspension of hepatocytes in Hanks medium, after 30 h of CCl 4 administration. Male Swiss adult mice (n = 15) served as donors of hepatocytes. The overall survival of animals in groups I to III was 100, 0, and 70%, respectively, by 2 wk of the study period. Transplanted hepatocytes were identified by Periodic Acid Schiff (PAS) staining and confirmed with a FISH technique using the Y-chromosome probe. The majority of exogenously transplanted hepatocytes were found in the liver and spleen sections even after 1 wk of hepatocyte transplantation. Transplanted cells were mostly found to be translocated into the sinusoids of the liver. Transplanted hepatocytes were found to be beneficial as a temporary liver support in a failing liver, significantly improving the survival of the animals. In the present study, the FISH technique was used to unequivocally distinguish the transplanted cells from the host, and thus describes a model for studying the distribution and survival of the transplanted cells.
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- 1998
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22. Understanding the context of balanced scorecard implementation: a hospital-based case study in pakistan
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Ajmal Agha, Jahan Firdous, Nabi Naheed, Razzak Junaid A, Jafri SM Wasim, Abbas Farhat, Lalji Sabrina NH, Rabbani Fauziah, Petzold Max, Brommels Mats, and Tomson Goran
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Medicine (General) ,R5-920 - Abstract
Abstract Background As a response to a changing operating environment, healthcare administrators are implementing modern management tools in their organizations. The balanced scorecard (BSC) is considered a viable tool in high-income countries to improve hospital performance. The BSC has not been applied to hospital settings in low-income countries nor has the context for implementation been examined. This study explored contextual perspectives in relation to BSC implementation in a Pakistani hospital. Methods Four clinical units of this hospital were involved in the BSC implementation based on their willingness to participate. Implementation included sensitization of units towards the BSC, developing specialty specific BSCs and reporting of performance based on the BSC during administrative meetings. Pettigrew and Whipp's context (why), process (how) and content (what) framework of strategic change was used to guide data collection and analysis. Data collection methods included quantitative tools (a validated culture assessment questionnaire) and qualitative approaches including key informant interviews and participant observation. Results Method triangulation provided common and contrasting results between the four units. A participatory culture, supportive leadership, financial and non-financial incentives, the presentation of clear direction by integrating support for the BSC in policies, resources, and routine activities emerged as desirable attributes for BSC implementation. The two units that lagged behind were more involved in direct inpatient care and carried a considerable clinical workload. Role clarification and consensus about the purpose and benefits of the BSC were noted as key strategies for overcoming implementation challenges in two clinical units that were relatively ahead in BSC implementation. It was noted that, rather than seeking to replace existing information systems, initiatives such as the BSC could be readily adopted if they are built on existing infrastructures and data networks. Conclusion Variable levels of the BSC implementation were observed in this study. Those intending to apply the BSC in other hospital settings need to ensure a participatory culture, clear institutional mandate, appropriate leadership support, proper reward and recognition system, and sensitization to BSC benefits.
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- 2011
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23. Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in mainland Tanzania, 2019.
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Ngasala BE, Chiduo MG, Mmbando BP, Francis FT, Bushukatale S, Makene T, Mandara CI, Ishengoma DS, Kamugisha E, Ahmed M, Mahende MK, Kavishe RA, Muro F, Molteni F, Reaves E, Kitojo C, Greer G, Nyinondi S, Kabula B, Lalji S, Chacky F, Njau RJ, Warsame M, and Mohamed A
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- Child, Humans, Infant, Artemether, Lumefantrine Drug Combination adverse effects, Tanzania, Reinfection chemically induced, Reinfection drug therapy, Prospective Studies, Drug Combinations, Artemether therapeutic use, Amodiaquine therapeutic use, Treatment Outcome, Plasmodium falciparum, Antimalarials adverse effects, Malaria, Falciparum drug therapy, Artemisinins adverse effects, Malaria drug therapy
- Abstract
Background: Artemisinin-based combination therapy (ACT) has been a major contributor to the substantial reductions in global malaria morbidity and mortality over the last decade. In Tanzania, artemether-lumefantrine (AL) was introduced as the first-line treatment for uncomplicated Plasmodium falciparum malaria in 2006. The World Health Organization (WHO) recommends regular assessment and monitoring of the efficacy of the first-line treatment, specifically considering that artemisinin resistance has been confirmed in the Greater Mekong sub-region. This study's main aim was to assess the efficacy and safety of AL for treating uncomplicated P. falciparum malaria in Tanzania., Methods: This was a single-arm prospective antimalarial drug efficacy trial conducted in four of the eight National Malaria Control Programme (NMCP) sentinel sites in 2019. The trial was carried out in outpatient health facilities in Karume-Mwanza region, Ipinda-Mbeya region, Simbo-Tabora region, and Nagaga-Mtwara region. Children aged six months to 10 years with microscopy confirmed uncomplicated P. falciparum malaria who met the inclusion criteria were recruited based on the WHO protocol. The children received AL (a 6-dose regimen of AL twice daily for three days). Clinical and parasitological parameters were monitored during follow-up over 28 days to evaluate drug efficacy., Results: A total of 628 children were screened for uncomplicated malaria, and 349 (55.6%) were enrolled between May and September 2019. Of the enrolled children, 343 (98.3%) completed the 28-day follow-up or attained the treatment outcomes. There were no early treatment failures; recurrent infections during follow-up were common at two sites (Karume 29.5%; Simbo 18.2%). PCR-corrected adequate clinical and parasitological response (ACPR) by survival analysis to AL on day 28 of follow-up varied from 97.7% at Karume to 100% at Ipinda and Nagaga sites. The commonly reported adverse events were cough, skin pallor, and abdominal pain. The drug was well tolerated, and no serious adverse event was reported., Conclusion: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria in Tanzania in 2019. The high recurrent infections were mainly due to new infections, highlighting the potential role of introducing alternative artemisinin-based combinations that offer improved post-treatment prophylaxis, such as artesunate-amodiaquine (ASAQ)., (© 2024. The Author(s).)
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- 2024
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24. Trends of insecticide resistance monitoring in mainland Tanzania, 2004-2020.
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Tungu P, Kabula B, Nkya T, Machafuko P, Sambu E, Batengana B, Sudi W, Derua YA, Mwingira V, Masue D, Malima R, Kitojo C, Serbantez N, Reaves EJ, Mwalimu C, Nhiga SL, Ally M, Mkali HR, Joseph JJ, Chan A, Ngondi J, Lalji S, Nyinondi S, Eckert E, Reithinger R, Magesa S, and Kisinza WN
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- Animals, Female, Humans, Insecticide Resistance, Tanzania, Mosquito Vectors, Mosquito Control methods, Anopheles, Malaria epidemiology, Malaria prevention & control, Pyrethrins pharmacology, Insecticides pharmacology
- Abstract
Background: Insecticide resistance is a serious threat to the continued effectiveness of insecticide-based malaria vector control measures, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). This paper describes trends and dynamics of insecticide resistance and its underlying mechanisms from annual resistance monitoring surveys on Anopheles gambiae sensu lato (s.l.) populations conducted across mainland Tanzania from 2004 to 2020., Methods: The World Health Organization (WHO) standard protocols were used to assess susceptibility of the wild female An. gambiae s.l. mosquitoes to insecticides, with mosquitoes exposed to diagnostic concentrations of permethrin, deltamethrin, lambdacyhalothrin, bendiocarb, and pirimiphos-methyl. WHO test papers at 5× and 10× the diagnostic concentrations were used to assess the intensity of resistance to pyrethroids; synergist tests using piperonyl butoxide (PBO) were carried out in sites where mosquitoes were found to be resistant to pyrethroids. To estimate insecticide resistance trends from 2004 to 2020, percentage mortalities from each site and time point were aggregated and regression analysis of mortality versus the Julian dates of bioassays was performed., Results: Percentage of sites with pyrethroid resistance increased from 0% in 2004 to more than 80% in the 2020, suggesting resistance has been spreading geographically. Results indicate a strong negative association (p = 0.0001) between pyrethroids susceptibility status and survey year. The regression model shows that by 2020 over 40% of An. gambiae mosquitoes survived exposure to pyrethroids at their respective diagnostic doses. A decreasing trend of An. gambiae susceptibility to bendiocarb was observed over time, but this was not statistically significant (p = 0.8413). Anopheles gambiae exhibited high level of susceptibility to the pirimiphos-methyl in sampled sites., Conclusions: Anopheles gambiae Tanzania's major malaria vector, is now resistant to pyrethroids across the country with resistance increasing in prevalence and intensity and has been spreading geographically. This calls for urgent action for efficient malaria vector control tools to sustain the gains obtained in malaria control. Strengthening insecticide resistance monitoring is important for its management through evidence generation for effective malaria vector control decision., (© 2023. The Author(s).)
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- 2023
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25. Spatiotemporal dynamics of malaria in Zanzibar, 2015-2020.
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Bisanzio D, Lalji S, Abbas FB, Ali MH, Hassan W, Mkali HR, Al-Mafazy AW, Joseph JJ, Nyinondi S, Kitojo C, Serbantez N, Reaves E, Eckert E, Ngondi JM, and Reithinger R
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- Humans, Tanzania epidemiology, Seasons, Malaria epidemiology
- Abstract
Background: Despite high coverage of malaria interventions, malaria elimination in Zanzibar remains elusive, with the annual number of cases increasing gradually over the last 3 years., Objective: The aims of the study were to (1) assess the spatiotemporal dynamics of malaria in Zanzibar between 2015 and 2020 and (2) identify malaria hotspots that would allow Zanzibar to develop an epidemiological stratification for more effective and granular intervention targeting., Methods: In this study, we analysed data routinely collected by Zanzibar's Malaria Case Notification (MCN) system. The system collects sociodemographic and epidemiological data from all malaria cases. Cases are passively detected at health facilities (ie, primary index cases) and through case follow-up and reactive case detection (ie, secondary cases). Analyses were performed to identify the spatial heterogeneity of case reporting at shehia (ward) level during transmission seasons., Results: From 1 January 2015 to 30 April 2020, the MCN system reported 22 686 index cases. Number of cases reported showed a declining trends from 2015 to 2016, followed by an increase from 2017 to 2020. More than 40% of cases had a travel history outside Zanzibar in the month prior to testing positive for malaria. The proportion of followed up index cases was approximately 70% for all years. Out of 387 shehias, 79 (20.4%) were identified as malaria hotspots in any given year; these hotspots reported 52% of all index cases during the study period. Of the 79 hotspot shehias, 12 were hotspots in more than 4 years, that is, considered temporally stable, reporting 14.5% of all index cases., Conclusions: Our findings confirm that the scale-up of malaria interventions has greatly reduced malaria transmission in Zanzibar since 2006. Analyses identified hotspots, some of which were stable across multiple years. Malaria efforts should progress from a universal intervention coverage approach to an approach that is more tailored to a select number of hotspot shehias., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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26. Halting the Canadian STRIDER randomised controlled trial of sildenafil for severe, early-onset fetal growth restriction: ethical, methodological, and pragmatic considerations.
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von Dadelszen P, Audibert F, Bujold E, Bone JN, Sandhu A, Li J, Kariya C, Chung Y, Lee T, Au K, Skoll MA, Vidler M, Magee LA, Piedboeuf B, Baker PN, Lalji S, and Lim KI
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- Canada, Female, Gestational Age, Humans, Placenta Growth Factor therapeutic use, Pregnancy, Randomized Controlled Trials as Topic, Sildenafil Citrate therapeutic use, Ultrasonography, Prenatal adverse effects, Fetal Growth Retardation chemically induced, Fetal Growth Retardation drug therapy, Umbilical Arteries diagnostic imaging
- Abstract
Objectives: To determine the efficacy and safety of sildenafil citrate to improve outcomes in pregnancies complicated by early-onset, dismal prognosis, fetal growth restriction (FGR). Eligibility: women ≥ 18 years, singleton, 18 + 0-27 + 6 weeks' gestation, estimated fetal weight < 700 g, low PLFG, and ≥ 1 of (i) abdominal circumference < 10th percentile for gestational age (GA); or (ii) reduced growth velocity and either abnormal uterine artery Doppler or prior early-onset FGR with adverse outcome. Ineligibility criteria included: planned termination or reversed umbilical artery end-diastolic flow. Eligibility confirmed by placental growth factor (PLGF) < 5 th percentile for GA measured post randomization. Women randomly received (1:1) either sildenafil 25 mg three times daily or matched placebo until either delivery or 31 + 6 weeks., Primary Outcome: delivery GA. The trial stopped early when Dutch STRIDER signalled potential harm; despite distinct eligibility criteria and IRB and DSMB support to continue, because of futility. NCT02442492 [registered 13/05/2015]., Results: Between May 2017 and June 2018, 21 (90 planned) women were randomised [10 sildenafil; 11 placebo (1 withdrawal)]. Baseline characteristics, PLGF levels, maternal and perinatal outcomes, and adverse events did not differ. Delivery GA: 26 + 6 weeks (sildenafil) vs 29 + 2 weeks (placebo); p = 0.200. Data will contribute to an individual participant data meta-analysis., (© 2022. The Author(s).)
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- 2022
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27. Cost-Effectiveness of Indoor Residual Spraying of Households with Insecticide for Malaria Prevention and Control in Tanzania.
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Stelmach R, Colaço R, Lalji S, McFarland D, and Reithinger R
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- Child, Preschool, Family Characteristics, Female, Humans, Infant, Insecticide Resistance, Malaria economics, Male, Mosquito Control instrumentation, Mosquito Control methods, Plasmodium falciparum, Prevalence, Tanzania epidemiology, Cost-Benefit Analysis, Insecticide-Treated Bednets economics, Insecticides economics, Malaria epidemiology, Malaria prevention & control, Mosquito Control economics
- Abstract
Using a decision-tree approach, we examined the cost-effectiveness of indoor residual spraying (IRS) of households with insecticide combined with insecticide-treated bed net (ITN) distribution (IRS + ITN), compared with ITN distribution alone in the programmatic context of mainland Tanzania. The primary outcome of our model was the expected economic cost to society per case of malaria averted in children ≤ 5 years of age. Indoor residual spraying of households with insecticide data came from a program implemented in northwest Tanzania from 2008 to 2012; all other data originated from the published literature. Through sensitivity and scenario analyses, the model also examined the effects of variations in insecticide resistance, malaria prevalence, and different IRS modalities. In the base case, IRS + ITN is expected to be more expensive and more effective than the ITN-only intervention (incremental cost-effectiveness ratio [ICER]: $152.36). The number of IRS rounds, IRS insecticide costs, ITN use, malaria prevalence, and the probability that a child develops symptoms following infection drove the interventions' cost-effectiveness. Compared with universal spraying, targeted spraying is expected to lead to a higher number of malaria cases per person targeted (0.211-0.256 versus 0.050-0.076), but the incremental cost per case of malaria averted is expected to be lower (ICER: $41.70). In a scenario of increasing pyrethroid resistance, the incremental expected cost per case of malaria averted is expected to increase compared with the base case (ICER: $192.12). Tanzania should pursue universal IRS only in those regions that report high malaria prevalence. If the cost per case of malaria averted of universal IRS exceeds the willingness to pay, targeted spraying could provide an alternative, but may result in higher malaria prevalence.
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- 2018
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28. Surveillance for sulfadoxine-pyrimethamine resistant malaria parasites in the Lake and Southern Zones, Tanzania, using pooling and next-generation sequencing.
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Ngondi JM, Ishengoma DS, Doctor SM, Thwai KL, Keeler C, Mkude S, Munishi OM, Willilo RA, Lalji S, Kaspar N, Kitojo C, Paxton LA, Hathaway NJ, Bailey JA, Juliano JJ, Meshnick SR, and Gutman J
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- Adolescent, Adult, Aged, Child, Child, Preschool, Cross-Sectional Studies, Drug Combinations, High-Throughput Nucleotide Sequencing, Humans, Infant, Malaria, Falciparum parasitology, Middle Aged, Mutation, Protozoan Proteins metabolism, Tanzania, Young Adult, Antimalarials pharmacology, Drug Resistance, Plasmodium falciparum drug effects, Protozoan Proteins genetics, Pyrimethamine pharmacology, Sulfadoxine pharmacology
- Abstract
Background: Malaria in pregnancy (MiP) remains a major public health challenge in areas of high malaria transmission. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended to prevent the adverse consequences of MiP. The effectiveness of SP for IPTp may be reduced in areas where the dhps581 mutation (a key marker of high level SP resistance) is found; this mutation was previously reported to be common in the Tanga Region of northern Tanzania, but there are limited data from other areas. The frequency of molecular markers of SP resistance was investigated in malaria parasites from febrile patients at health centres (HC) in seven regions comprising the Lake and Southern Zones of mainland Tanzania as part of the ongoing efforts to generate national-wide data of SP resistance., Methods: A cross-sectional survey was conducted in the outpatient departments of 14 HCs in seven regions from April to June, 2015. 1750 dried blood spot (DBS) samples were collected (117 to 160 per facility) from consenting patients with positive rapid diagnostic tests for malaria, and no recent (within past 2 months) exposure to SP or related drugs. DNA was extracted from the DBS, pooled by HC, and underwent pooled targeted amplicon deep sequencing to yield estimates of mutated parasite allele frequency at each locus of interest., Results: The dhps540 mutation was common across all 14 sites, ranging from 55 to 98.4% of sequences obtained. Frequency of the dhps581 mutation ranged from 0 to 2.4%, except at Kayanga HC (Kagera Region, Lake Zone) where 24.9% of sequences obtained were mutated. The dhfr164 mutation was detected only at Kanyanga HC (0.06%)., Conclusion: By pooling DNA extracts, the allele frequency of mutations in 14 sites could be directly determined on a single deep-sequencing run. The dhps540 mutant was very common at all locations. Surprisingly, the dhps581 was common at one health center, but rare in all the others, suggesting that there is geographic micro-heterogeneity in mutant distribution and that accurate surveillance requires inclusion of multiple sites. A better understanding of the effect of the dhps581 mutant on the efficacy of IPTp-SP is needed.
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- 2017
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29. Evaluation of the safety and efficacy of a monopolar nonablative radiofrequency device for the improvement of vulvo-vaginal laxity and urinary incontinence.
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Lalji S and Lozanova P
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- Adult, Aged, Electric Stimulation Therapy adverse effects, Female, Humans, Middle Aged, Prospective Studies, Treatment Outcome, Electric Stimulation Therapy instrumentation, Sexual Dysfunction, Physiological therapy, Urinary Incontinence, Stress therapy, Vagina physiopathology, Vulva physiopathology
- Abstract
Background and Objective: Vaginal childbirth, natural process of aging, congenital factors, and surgical interventions are considered the main causes of vulvo-vaginal laxity driven by changes in collagen and elastin fibers. This causes a loss of strength and flexibility within the vaginal wall. As a result, women may experience lack of sensation and stress urinary incontinence (SUI)-the condition of involuntary loss of urine associated with activities that cause an increase in intra-abdominal pressure (eg, sneezing, coughing, and lifting). Both vaginal laxity and urinary incontinence significantly affect patients' quality of life (QoL). The aim of this study was to evaluate efficacy and safety of a noninvasive radiofrequency device when used to treat SUI and vulvo-vaginal laxity through its heating effect which stimulates collagen and elastin fibers., Methods: Twenty-seven women (average age 44.78±10.04 years) with indications of mild/moderate SUI as well as vulvo-vaginal laxity were treated with a monopolar radiofrequency device. The treatment course consisted of three once-a-week sessions. Each session included intravaginal treatment followed by treatment of labia majora and the perineum. Improvement in the SUI condition was evaluated by applying the International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF). Data were collected at the baseline, after the last treatment and at 1-month follow-up visit. Vaginal laxity was assessed by subjective vulvo-vaginal laxity questionnaire (VVLQ). Data were collected before the 1st treatment and during the 1-month follow-up visit. Patient's satisfaction was recorded using a satisfaction questionnaire. Data were collected after the last treatment and at the 1-month follow-up visit. Any adverse events related to the treatments were monitored., Results: On a scale of 0 to 5, the average frequency of urine leak improved from "2-3 times a week" (2.15±1.03 points prior to treatment) to "once a week" (1.00±0.78 points post-treatment), and on to "never" (0.44±0.51 points at the 1-month follow-up visit). Sixteen subjects (59.3%) reported decrease in the amount of leakage, with 15 women (55.6%) becoming completely leak-free at the 1-month follow-up. At the 1-month follow-up visit, 24 subjects (88.9%) expressed their condition's interference with everyday life decreased and 17 patients (62.9%) said the condition did not interfere with their everyday life at all as a result of the treatment. All results are statistically significant (P<.05). No adverse events were recorded. All subjects reported improvement in vaginal laxity, from average perception of "very loose" (2.19±1.08 points prior to treatment) to "moderately tight" (5.74±0.76 points at the 1-month follow-up visit). During the follow-up visit, 89% of the patients "agreed" or "strongly agreed" that their SUI condition improved, and 93% of the patients "agreed" or "strongly agreed" that their gratification during intercourse improved. None of the subjects reported dissatisfaction., Conclusion: The study confirmed the monopolar radiofrequency method as an effective and safe treatment of SUI and vulvo-vaginal laxity. The treatments were well tolerated by all subjects with no adverse effects., (© The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.)
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- 2017
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30. Taking local ownership: government and household contribution to indoor residual spraying in Zanzibar and mainland Tanzania.
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Alidina Z, Colaco R, Ali AS, Mcha JH, Mwalimu CD, Thawer NG, Lalji S, Mutagahywa J, Ramsan MM, Kafuko JM, Kaspar N, Magesa SM, Reithinger R, and Ngondi JM
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- Family Characteristics, Humans, Tanzania, Federal Government, Financing, Government methods, Financing, Organized methods, Local Government, Malaria prevention & control, Mosquito Control economics, Ownership economics
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Background: While donor funding is instrumental in initiation and implementation of malaria control efforts, national government contributions are key to local ownership and sustainability. This study explored in-kind contributions of local government and households towards the cost of indoor residual spraying (IRS) interventions in Tanzania., Methods: Data were collected through interviews with local government officials and technical teams in the IRS project. Household contribution was based on provision of water for IRS. Government contributions included government-provided warehouse and office space, vehicles, and staff labour. In-kind contributions were aggregated at the district, regional and national level. Calculations were based on proportion of total costs of IRS from 2010 to 2012., Results: The mainland government provided larger amounts of in-kind contribution in absolute value (mean of US$454 200) compared to Zanzibar (US$89 163). On average, in-kind contribution was 5.5% of total costs in Zanzibar and 2.9% in mainland. The proportion of government in-kind contribution was higher in Zanzibar versus the mainland (86% vs 50%) while household contribution was higher in mainland compared to Zanzibar (50% vs 14%)., Conclusion: Government involvement, particularly through budgetary allocations and increased in-kind contribution, needs to be encouraged for malaria control efforts to be locally owned, managed and sustained., (© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2016
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31. School Distribution as Keep-Up Strategy to Maintain Universal Coverage of Long-Lasting Insecticidal Nets: Implementation and Results of a Program in Southern Tanzania.
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Lalji S, Ngondi JM, Thawer NG, Tembo A, Mandike R, Mohamed A, Chacky F, Mwalimu CD, Greer G, Kaspar N, Kramer K, Mlay B, Issa K, Lweikiza J, Mutafungwa A, Nzowa M, Willilo RA, Nyoni W, Dadi D, Ramsan MM, Reithinger R, and Magesa SM
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- Adolescent, Adult, Child, Preschool, Female, Government Programs, Humans, Male, Pilot Projects, Residence Characteristics, Tanzania, Health Promotion, Insecticide-Treated Bednets, Insecticides, Malaria prevention & control, Mosquito Control, Ownership, Schools
- Abstract
Tanzania successfully scaled up coverage of long-lasting insecticidal nets (LLINs) through mass campaigns. To sustain these gains, a school-based approach was piloted in the country's Southern Zone starting in 2013, called the School Net Program 1 (SNP1). We report on the design, implementation, monitoring, and outputs of the second round (SNP2) undertaken in 2014. SNP2 was conducted in all schools in Lindi, Mtwara, and Ruvuma regions, targeting students in primary (Standards 1, 3, 5, and 7) and secondary (Forms 2 and 4) schools and all teachers. In Lindi region, 2 additional classes (Standards 2 and 4) were targeted. LLIN distribution data were managed using an Android software application called SchoolNet. SNP2 included 2,337 schools, 473,700 students, and 25,269 teachers. A total of 5,070 people were trained in LLIN distribution (487 trainers and 4,583 distributors), and 4,392 (434 ward and 3,958 village) community change agents undertook sensitization and mobilization. A total of 507,775 LLINs were distributed to schools, with 464,510 (97.9% of those registered) students and 24,206 (95.8% of those registered) school teachers receiving LLINs. LLIN ownership and use is expected to have increased, potentially further reducing the burden of malaria in the Southern Zone of Tanzania., (© Lalji et al.)
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- 2016
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32. Use of insecticide quantification kits to investigate the quality of spraying and decay rate of bendiocarb on different wall surfaces in Kagera region, Tanzania.
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Thawer NG, Ngondi JM, Mugalura FE, Emmanuel I, Mwalimu CD, Morou E, Vontas J, Protopopoff N, Rowland M, Mutagahywa J, Lalji S, Molteni F, Ramsan MM, Willilo R, Wright A, Kafuko JM, Ndong I, Reithinger R, and Magesa SM
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- Animals, Housing, Mosquito Control methods, Surface Properties, Tanzania, Chemistry Techniques, Analytical methods, Insecticides chemistry, Insecticides pharmacology, Phenylcarbamates chemistry, Phenylcarbamates pharmacology
- Abstract
Background: Bendiocarb was introduced for the first time for Indoor Residual Spraying (IRS) in Tanzania in 2012 as part of the interim national insecticide resistance management plan. This move followed reports of increasingly alarming levels of pyrethroid resistance across the country. This study used the insecticide quantification kit (IQK) to investigate the intra-operational IRS coverage and quality of spraying, and decay rate of bendiocarb on different wall surfaces in Kagera region., Methods: To assess intra-operational IRS coverage and quality of spraying, 104 houses were randomly selected out of 161,414 sprayed houses. A total of 509 samples (218 in Muleba and 291 in Karagwe) were obtained by scraping the insecticide samples from wall surfaces. To investigate decay rate, 66 houses (36 in Muleba and 30 in Karagwe) were selected and samples were collected monthly for a period of five months. Laboratory testing of insecticide concentration was done using IQK(TM) [Innovative Vector Control Consortium]., Results: Of the 509 samples, 89.5% met the World Health Organization (WHO) recommended concentration (between 100-400 mg/m(2)) for IRS target dosage. The proportion of samples meeting WHO standards varied between Karagwe (84.3%) and Muleba (96.3%) (p < 0.001). Assessment of quality of spraying at house level revealed that Muleba (84.8%) had a significantly higher proportion of households that met the expected target dosage (100-400 mg/m(2)) compared to Karagwe (68.9%) (p < 0.001). The quality of spraying varied across different wall substrates in both districts. Evaluation of bendiocarb decay showed that the proportion of houses with recommended concentration declined from 96.9%, 93.5% and 76.2% at months one, two, and three post IRS, respectively (p-trend = 0.03). The rate of decay increased in the fourth and fifth month post spraying with only 55.9% and 26.3% houses meeting the WHO recommendations, respectively., Conclusion: IQK is an important tool for assessing IRS coverage and quality of spraying. The study found adequate coverage of IRS; however, residual life of bendiocarb was observed to be three months. Results suggest that in order to maintain the recommended concentrations with bendiocarb, a second spray cycle should be carried out after three months.
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- 2015
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33. PIERS proteinuria: relationship with adverse maternal and perinatal outcome.
- Author
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Payne B, Magee LA, Côté AM, Hutcheon JA, Li J, Kyle PM, Menzies JM, Peter Moore M, Parker C, Pullar B, von Dadelszen P, Walters BN, von Dadelszen P, Magee LA, Douglas MJ, Walley KR, Russell JA, Lee SK, Gruslin A, Smith GN, Côté AM, Moutquin JM, Brown MA, Davis G, Walters BN, Sass N, Duan T, Zhou J, Mahajan S, Noovao A, McCowan LA, Kyle P, Moore MP, Bhutta SZ, Bhutta ZA, Hall, Steyn DW, Broughton Pipkin F, Loughna P, Robson S, de Swiet M, Walker JJ, Grobman WA, Lindheimer MD, Roberts JM, Mark Ansermino J, Benton S, Cundiff G, Hugo D, Joseph KS, Lalji S, Li J, Lott P, Ouellet AB, Shaw D, Keith Still D, Tawagi G, Wagner B, Biryabarema C, Mirembe F, Nakimuli A, Tsigas E, Merialdi M, and Widmer M
- Subjects
- Adult, Cohort Studies, Creatinine urine, Female, Gestational Age, Humans, Pre-Eclampsia diagnosis, Pregnancy, Prospective Studies, ROC Curve, Reagent Strips, Risk Factors, Urine Specimen Collection methods, Pre-Eclampsia urine, Pregnancy Outcome, Proteinuria diagnosis
- Abstract
Objective: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes., Methods: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments., Results: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome., Conclusion: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.
- Published
- 2011
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34. Acceptance of a rapid herpes test in labour: survey of attitudes of patients and health care providers.
- Author
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van Schalkwyk J, Amiri N, Lalji S, Gardella C, Wald A, and Money D
- Subjects
- Cross-Sectional Studies, DNA, Viral analysis, Female, Humans, Polymerase Chain Reaction methods, Pregnancy, Pregnancy Complications, Infectious diagnosis, Surveys and Questionnaires, Attitude of Health Personnel, Attitude to Health, Herpes Simplex diagnosis, Labor, Obstetric
- Abstract
Objective: To determine the acceptability to pregnant women and their health care providers of a rapid test for genital herpes simplex virus (HSV) in labour., Methods: A cross-sectional survey was conducted with outpatient pregnant women and their health care providers (obstetricians, family physicians and midwives) at BC Women's Hospital and Health Centre., Results: Of pregnant women approached, 207 (92%) completed the survey; 90% reported no history of genital herpes. Rapid HSV testing in labour was acceptable to 85% of pregnant women. Among the 133 women who were planning a vaginal delivery, 63% were willing to consider delivery by Caesarean section and 53% were willing to consider intrapartum anti-viral medications if HSV was present in the genital tract. Of 51 health care providers surveyed, 98% indicated interest in knowing if their patient had a newly acquired HSV infection, while 84% indicated interest in knowing if the patient had a reactivation of infection. If HSV was detected in their patient's genital tract, 36% indicated they would recommend a Caesarean section, and 25% would consider antiviral medication as an investigational intrapartum treatment. Interestingly, both of these proportions increased if the patient had ruptured membranes for more than four hours., Conclusion: Most pregnant women and their health care providers are receptive to the use of a rapid polymerase chain reaction test to detect genital HSV shedding in labour. This supports the development of HSV rapid testing and antiviral therapy trials in the labour setting.
- Published
- 2008
- Full Text
- View/download PDF
35. The evaluation of the fetal fibronectin test for prediction of preterm delivery in symptomatic patients.
- Author
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Skoll A, St Louis P, Amiri N, Delisle MF, and Lalji S
- Subjects
- Cervix Mucus chemistry, Female, Humans, Predictive Value of Tests, Pregnancy, Prospective Studies, Sensitivity and Specificity, Single-Blind Method, Fibronectins analysis, Glycoproteins analysis, Obstetric Labor, Premature diagnosis
- Abstract
Objective: This study was conducted to evaluate the usefulness of testing for fetal fibronectin (fFN) to rule out the diagnosis of preterm labour in symptomatic patients in a Canadian setting., Methods: This was a prospective, blinded clinical evaluation of fFN testing in women presenting with threatened preterm labour at between 24 and 34 weeks' gestation at two Canadian tertiary care centres., Results: Of the 149 women tested, 32 had a positive fFN test. In the total patient population, 10.1% delivered within seven days of testing, and 18.2% delivered prior to 34 weeks. A negative fFN result was associated with a 97.4% likelihood of delivering more than seven days after testing and with a 91.4% chance of delivering after 34 weeks., Conclusion: The fFN test appears to provide useful information in the risk assessment of Canadian women presenting with symptoms compatible with preterm labour. A negative test has a high predictive value for delivering more than seven days after presentation.
- Published
- 2006
- Full Text
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36. Formulation development and antitumor activity of a filter-sterilizable emulsion of paclitaxel.
- Author
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Constantinides PP, Lambert KJ, Tustian AK, Schneider B, Lalji S, Ma W, Wentzel B, Kessler D, Worah D, and Quay SC
- Subjects
- Animals, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic pharmacokinetics, Dose-Response Relationship, Drug, Emulsions, Female, Filtration, Humans, Melanoma drug therapy, Melanoma mortality, Mice, Mice, Inbred Strains, Paclitaxel chemistry, Paclitaxel pharmacokinetics, Paclitaxel pharmacology, Particle Size, Serum Albumin pharmacology, Skin Neoplasms drug therapy, Skin Neoplasms mortality, Solubility, Sterilization, Survival Analysis, Vitamin E pharmacology, Antineoplastic Agents, Phytogenic toxicity, Chemistry, Pharmaceutical, Paclitaxel toxicity
- Abstract
Purpose: Paclitaxel is currently administered i.v. as a slow infusion of a solution of the drug in an ethanol:surfactant:saline admixture. However, poor solubilization and toxicity are associated with this drug therapy. Alternative drug delivery systems, including parenteral emulsions, are under development in recent years to reduce drug toxicity, improve efficacy and eliminate premedication., Methods: Paclitaxel emulsions were prepared by high-shear homogenization. The particle size of the emulsions was measured by dynamic light scattering. Drug concentration was quantified by HPLC and in vitro drug release was monitored by membrane dialysis. The physical stability of emulsions was monitored by particle size changes in both the mean droplet diameter and 99% cumulative distribution. Paclitaxel potency and changes in the concentration of known degradants were used as chemical stability indicators. Single dose acute toxicity studies were conducted in healthy mice and efficacy studies in B 16 melanoma tumor-bearing mice., Results: QW8184, a physically and chemically stable sub-micron oil-in-water (o/w) emulsion of paclitaxel, can be prepared at high drug loading (8-10 mg/mL) having a mean droplet diameter of <100 nm and 99% cumulative particle size distribution of <200 nm. In vitro release studies demonstrated low and sustained drug release both in the presence and absence of human serum albumin. Based on single dose acute toxicity studies, QW8184 is well tolerated both in mice and rats with about a 3-fold increase in the maximum-tolerated-dose (MTD) over the current marketed drug formulation. Using the B16 mouse melanoma model, a significant improvement in drug efficacy was observed with QW8184 over Taxol., Conclusions: QW8184, a stable sub-micron o/w emulsion of paclitaxel has been developed that can be filter-sterilized and administered i.v. as a bolus dose. When compared to Taxol, this emulsion exhibited reduced toxicity and improved efficacy most likely due to the composition and dependent physicochemical characteristics of the emulsion.
- Published
- 2000
- Full Text
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