Molecular and physiologic changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first-ever all civilian crew to low Earth orbit, which included the youngest American astronaut (age 29), novel in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables, and immune profiling), ocular alignment measurements, and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiologic, and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

Large magnetic gap at the Dirac point in Bi2Te3/MnBi2Te4 heterostructures.

Magnetically doped topological insulators enable the quantum anomalous Hall effect (QAHE), which provides quantized edge states for lossless charge-transport applications1-8. The edge states are hosted by a magnetic energy gap at the Dirac point2, but hitherto all attempts to observe this gap directly have been unsuccessful. Observing the gap is considered to be essential to overcoming the limitations of the QAHE, which so far occurs only at temperatures that are one to two orders of magnitude below the ferromagnetic Curie temperature, TC (ref. 8). Here we use low-temperature photoelectron spectroscopy to unambiguously reveal the magnetic gap of Mn-doped Bi2Te3, which displays ferromagnetic out-of-plane spin texture and opens up only below TC. Surprisingly, our analysis reveals large gap sizes at 1 kelvin of up to 90 millielectronvolts, which is five times larger than theoretically predicted9. Using multiscale analysis we show that this enhancement is due to a remarkable structure modification induced by Mn doping: instead of a disordered impurity system, a self-organized alternating sequence of MnBi2Te4 septuple and Bi2Te3 quintuple layers is formed. This enhances the wavefunction overlap and size of the magnetic gap10. Mn-doped Bi2Se3 (ref. 11) and Mn-doped Sb2Te3 form similar heterostructures, but for Bi2Se3 only a nonmagnetic gap is formed and the magnetization is in the surface plane. This is explained by the smaller spin-orbit interaction by comparison with Mn-doped Bi2Te3. Our findings provide insights that will be crucial in pushing lossless transport in topological insulators towards room-temperature applications.

Plummeting toxic contaminates from water through phycoremediation: Mechanism, influencing factors and future outlook to enhance the capacity of living and non-living algae.

Freshwater habitats hold a unique role in the survival of all living organisms and supply water for drinking, irrigation, and life support activities. In recent decades, due to anthropogenic activities, deterioration in the water quality has been a long-lasting problem and challenge to the scientific fraternity. Although, these freshwater bodies have a bearable intrinsic capacity for pollution load however alarming increase in pollution limits the intrinsic capacities and requires additional technological interventions. The release of secondary pollutants from conventional interventions further needs revisiting the existing methodologies and asking for green interventions. Green interventions such as phycoremediation are natural, eco-friendly, economic, and energy-efficient alternatives and provide additional benefits such as nutrient recovery, biofuel production, and valuable secondary metabolites from polluted freshwater bodies. This systemic review in a nut-shell comprises the recent research insights on phycoremediation, technological implications, and influencing factors, and further discusses the associated mechanisms of metal ions biosorption by living and non-living algae, its advantages, and limitations. Besides, the article explores the possibility of future research prospects for applicability at a field scale that will help in the efficient utilization of resources, and improved ecological and health risks.

Assessment of early morning serum cortisol levels in adult male patients with alcohol-related disorders.

BACKGROUND: Alcohol-related disorders are a major health problem among Indian male professionals because of the unique nature of socioeconomic and demographic conditions. Various studies have highlighted the association between alcohol-related disorders and hypothalamic-pituitary-adrenal (HPA) axis dysfunction, but the evidence accrued so far is inconclusive. In our study, we have assessed early morning serum total cortisol concentration among Indian adult male population affected with alcohol-related disorder. METHODS: A case-based cross-sectional study in which all consecutive patients admitted in the psychiatry ward of a tertiary care hospital with diagnosis of 'alcohol-related disorders', who were meeting all the inclusion criteria, and who had none of the exclusion criteria were part of the study. Diseased controls and healthy controls were chosen by applying strict inclusion and exclusion criteria. Serum early morning (0400 h) total cortisol levels were estimated using automated quantitative enzyme-linked fluorescent assay technique. RESULTS: 98 psychiatric patients and 50 healthy controls were evaluated. Out of these 98 patients 66 patients were diagnosed cases of alcohol-related disorder. Morning serum total cortisol levels in patients with alcohol-related disorders was found to be significantly different from healthy controls. CONCLUSION: Our study suggests that alcohol-related disorders are associated with chronic changes in HPA axis and significant alteration of early morning serum total cortisol levels were demonstrated in this group of patients.

Genotyping for Dombrock blood group alleles in Northern Pakistani blood donors.

Genotyping can be used to identify rare blood group antigens and to solve suspected blood group discrepancies, particularly when serologic methods are limited. Unfortunately, only a few such studies have been performed in Pakistan. The present study was conducted to determine the frequency of Dombrock blood group alleles by genotyping samples from blood donors from the north of Pakistan. Blood samples were taken with consent from 300 blood donors; DNA was extracted and tested for DO*01 and DO*02 alleles by sequence-specific primer polymerase chain reaction (PCR-SSP), followed by gel electrophoresis. Allele frequencies were calculated. The observed and expected genotype frequencies were compared using the χ2 test. The allele frequencies for DO*01 and DO*02 were 0.40 and 0.60, respectively. Genotype frequencies were in Hardy-Weinberg equilibrium. This study in Pakistani blood donors provides Dombrock blood group allele frequencies by PCR-SSP. This approach is efficient and economical and can be applied in developing countries. The findings can contribute to the development of in-house red blood cell panels, identification of rare blood types, and establishment of a national rare blood donor program.Genotyping can be used to identify rare blood group antigens and to solve suspected blood group discrepancies, particularly when serologic methods are limited. Unfortunately, only a few such studies have been performed in Pakistan. The present study was conducted to determine the frequency of Dombrock blood group alleles by genotyping samples from blood donors from the north of Pakistan. Blood samples were taken with consent from 300 blood donors; DNA was extracted and tested for DO*01 and DO*02 alleles by sequence-specific primer polymerase chain reaction (PCR-SSP), followed by gel electrophoresis. Allele frequencies were calculated. The observed and expected genotype frequencies were compared using the χ2 test. The allele frequencies for DO*01 and DO*02 were 0.40 and 0.60, respectively. Genotype frequencies were in Hardy-Weinberg equilibrium. This study in Pakistani blood donors provides Dombrock blood group allele frequencies by PCR-SSP. This approach is efficient and economical and can be applied in developing countries. The findings can contribute to the development of in-house red blood cell panels, identification of rare blood types, and establishment of a national rare blood donor program.

Can a virtual microbiology simulation be as effective as the traditional Wetlab for pharmacy student education?

BACKGROUND: Pharmacy practice education requires the development of proficiencies and an understanding of clinical microbiology. Learning in this area could be delivered using practical laboratory exercises, or potentially, simulation-based education. Simulation has previously successfully enhanced learning in health professional education. The current global climate due to COVID-19 has further highlighted the important role of technology-enhanced learning in delivering outcomes that meet the requisite learning objectives of a course. The aim of the present study was to compare the impact of a commercially available virtual microbiology simulation (VUMIE™) with a traditional wet laboratory (wetlab) on learner knowledge, skills and confidence in a second-year integrated pharmacotherapeutics course for Bachelor of Pharmacy students. METHODS: A randomised, crossover study was employed to determine whether the simulation intervention (VUMIE™) improves learning outcomes (knowledge, skills and confidence) of pharmacy students, when compared to a traditional wetlab intervention. Each student completed three 1-2 h length sessions, for both the wetlab and VUMIE™ interventions (6 sessions total). Data was collected using surveys deployed at baseline (pre-interventions), post-intervention 1 or 2 (VUMIE™ or wetlab) and endpoint (post-interventions 1 and 2). Statistical analysis was conducted using SPSS Statistics 25 and Instat™ software. RESULTS: Response rates were approximately 50% at initial survey and approximately 25% at endpoint survey. VUMIE™ produced higher post-intervention knowledge scores for the multiple-choice questions compared to the wetlab, however, the highest score was achieved at endpoint. Both interventions produced statistically significant differences for mean scores compared to baseline (pre-VUMIE™ and wetlab) across the domains of knowledge, skills and confidence. VUMIE™ produced higher post-intervention mean scores for knowledge, skills and confidence compared to post-intervention mean scores for the wetlab, however there was no statistical significance between the mean score for the two interventions, thus the VUMIE™ activity produced learning outcomes comparable to the wetlab activity. CONCLUSION: These findings suggest VUMIE™ provides similar effects on students' knowledge, skills, and confidence as a wetlab. The simulation's implementation was not cost-prohibitive, provided students with a physically and psychologically safe learning environment, and the benefit of being able to repeat activities, supporting deliberate practice.

Knowledge, attitudes, and perceptions related to telemedicine among young doctors and nursing staff at the King Abdul-Aziz University Hospital Jeddah, KSA.

OBJECTIVE: To investigate the knowledge, perceptions, and attitude of young doctors and nurses at Kind Abdulaziz University Hospital (KAUH) Jeddah, KSA, regarding the effectiveness of telemedicine in dealing with the patients for either follow-up or continuous monitoring of chronic diseases. MATERIAL AND METHODS: This prospective cross-sectional study was carried out on the young doctors and nursing staff at KAUH. An online questionnaire addressing all the required fields, i.e., background essential demography, perceptions, acceptance, and knowledge regarding telemedicine's utility, was sent to the targeted population of health care workers. Completed responses were analyzed statistically as per study objectives. RESULTS: The response rate in our study was 85%. A total of 335 participants responded to our questionnaire. One hundred seventy-one (51.1%) were doctors, whereas one hundred sixty-four (48.9%) were the nursing staff. Among doctors, 50 (29.4%) were recent graduates, whereas, in the nursing side, 77 (46.7%) were the senior nursing students. The knowledge and attitude of the young nursing staff were relatively better than the senior staff taking part in the study and the trends were found statistically significant. CONCLUSION: Our study participants, being young, were enthusiastic, had good knowledge regarding the advantages and limitations of telemedicine in managing the selected groups of patients. Their perception and attitude were quite positive. This is an encouraging trend in the promotion of telemedicine as an established way of managing patients with special requirements in an effective way. The ongoing COVID-19 pandemic has highlighted the importance of telemedicine in emergencies to protect both patients and health care workers by reducing chronic patients' avoidable hospital visits.

Assessing a thermal spike model of swift heavy ion-matter interactions via Pd1-xNix/Si interface mixing.

The thermal spike model (TSM), a widely accepted mechanism of swift heavy ion (SHI)-matter interactions, provides explanation for various SHI induced effects, including mixing across interfaces. We assess the validity of the model via tuning the electron-phonon coupling strength (G) by taking a series Pd1-xNix of a completely solid soluble binary, and then observing Pd1-xNix/Si interface mixing induced by a combination of 100 MeV Au ion irradiation and 4 keV Ar ion sputtering. If the TSM truly describes the SHI-matter interaction mechanism, any non-linearity in x-variation of G must also result in a similar non-linearity in the x-dependence of mixing. Experimentally, the extent of mixing has been parametrized by the irradiation induced change Δσ2 in variances of Pd and Ni depth profiles derived from XPS. Computationally, G determined using density functional theory has been used to solve the equations appropriate to the TSM, and then an equivalent quantity L2, proportional to Δσ2, has been calculated. Both Δσ2(x) and L2(x) show non-linearities, albeit in slightly dissimilar ways, leading to a conjecture that the present work at least does not invalidate the TSM.

Irradiation-Induced Compositional Effects on Human Bone After Extracorporeal Therapy for Bone Sarcoma.

The present study investigates Raman scattering of human bone irradiated with 50 Gy single dose during therapeutic treatment of Ewing and Osteosarcoma. Bone quality was evaluated via mineral-to-matrix ratio, degree of crystallinity, change in amount of calcium, and carbonate substitution. Alteration in collagen and its cross-links was quantified through second-derivative deconvolution of Amide I peak. A dose of 50 Gy radiation leads to almost 50% loss of mineral content, while maintaining mineral crystallinity, and small changes in carbonate substitution. Deconvolution of Amide I suggested modifications in collagen structure via increase in amount of enzymatic trivalent cross-linking (p < 0.05). Overall irradiation led to detrimental effect on bone quality via changes in its composition, consequently reducing its elastic modulus with increased plasticity. The study thus quantifies effect of single-dose 50 Gy radiation on human bone, which in turn is necessary for designing improved radiation dosage during ECRT and for better understanding post-operative care.

Mutation in Phospholipase C, δ1 (PLCD1) Gene Underlies Hereditary Leukonychia in a Pashtun Family and Review of the Literature.

Human hereditary leukonychia is a rare nail disorder characterized by nail plates whitening on all finger and toe nails. Inheritance pattern is both autosomal dominant and recessive. To date, the only gene, phospholipase C, δ1 (PLCD1), on chromosome 3p22.2 has been reported to be involved in hereditary leukonychia. In the present study, a family of Pakhtun ethnicity, carrying leukonychia phenotype was investigated. The family inherited the phenotype in an autosomal dominant fashion. Affected individuals exhibited characteristic features of hereditary leukonychia with involvement of nails on both the hands and feet. Sequence analysis of DNA detected a p.Cys209Arg mutation, reported for the first time in a Pakistani Pashtun family.

Strain engineering of electronic structures and photocatalytic responses of MXenes functionalized by oxygen.

The structural, electronic, and photocatalytic properties of two-dimensional Ti2CO2, Zr2CO2, and Hf2CO2 MXenes were investigated by first-principles (PBE and hybrid) calculations. Transition from an indirect to a direct band gap was achieved for the biaxial tensile strain of 3% for Ti2CO2, 8% for Zr2CO2, and 13% for Hf2CO2 while the nature of the band gap remained indirect in the case of the compressive strain. The size of the band gap passed through a maximum under tensile strain and decreased monotonically under compressive strain. Analysis of Bader charge distribution showed that the tensile strain decreased the transfer of charge from the Ti, Zr, and Hf atoms to the C atom. Phonon spectra suggested that these systems are stable under a wide range of strains from compression to tension. The photocatalytic properties showed that unstrained and biaxial tensile strained Ti2CO2, Zr2CO2, and Hf2CO2 systems can be used to oxidize H2O into O2.

Calpain activation by ROS mediates human ether-a-go-go-related gene protein degradation by intermittent hypoxia.

Human ether-a-go-go-related gene (hERG) channels conduct delayed rectifier K(+) current. However, little information is available on physiological situations affecting hERG channel protein and function. In the present study we examined the effects of intermittent hypoxia (IH), which is a hallmark manifestation of sleep apnea, on hERG channel protein and function. Experiments were performed on SH-SY5Y neuroblastoma cells, which express hERG protein. Cells were exposed to IH consisting of alternating cycles of 30 s of hypoxia (1.5% O2) and 5 min of 20% O2. IH decreased hERG protein expression in a stimulus-dependent manner. A similar reduction in hERG protein was also seen in adrenal medullary chromaffin cells from IH-exposed neonatal rats. The decreased hERG protein was associated with attenuated hERG K(+) current. IH-evoked hERG protein degradation was not due to reduced transcription or increased proteosome/lysomal degradation. Rather it was mediated by calcium-activated calpain proteases. Both COOH- and NH2-terminal sequences of the hERG protein were the targets of calpain-dependent degradation. IH increased reactive oxygen species (ROS) levels, intracellular Ca(2+) concentration ([Ca(2+)]i), calpain enzyme activity, and hERG protein degradation, and all these effects were prevented by manganese-(111)-tetrakis-(1-methyl-4-pyridyl)-porphyrin pentachloride, a membrane-permeable ROS scavenger. These results demonstrate that activation of calpains by ROS-dependent elevation of [Ca(2+)]i mediates hERG protein degradation by IH.

Genetics of human Bardet-Biedl syndrome, an updates.

Bardet-Biedl syndrome (BBS) is an autosomal recessive multisystemic human genetic disorder characterized by six major defects including obesity, mental retardation, renal anomalies, polydactyly, retinal degeneration and hypogenitalism. In several cases of BBS, few other features such as metabolic defects, cardiovascular anomalies, speech deficits, hearing loss, hypertension, hepatic defects and high incidence of diabetes mellitus have been reported as well. The BBS displays extensive genetic heterogeneity. To date, 19 genes have been mapped on different chromosomes causing BBS phenotypes having varied mutational load of each BBS gene. In this review, we have discussed clinical spectrum and genetics of BBS. This report presents a concise overview of the current knowledge on clinical data and its molecular genetics progress upto date.

Simulator evaluation of a prototype device to reduce medication errors in anaesthesia.

We undertook a randomised control led trial to evaluate the effect of a prototype device which attaches to the intravenous drug administration port, and allows injection of intravenous drugs only after the user scans the barcode on the syringe label. This requires two steps: first, that the correct drug label is generated; and second, that the syringe-with-label is scanned before administration. Ten anaesthetists, who were unaware of the primary outcome being measured, administered general anaesthesia for two simulated standardised cases each without and with our prototype (control and intervention, respectively). The primary outcome measured was compliance with a safe drug administration procedure (defined as a two-step procedure where, step one is scanning a drug ampoule to print a label for a syringe and step two is scanning of the labelled syringe before administering it intravenously). A total of 182 intravenous drug administrations occurred in the study (91 in each group). We found that the use of our prototype increased safe drug administration behaviour in experienced anaesthetists; 33 (36.3% [95% CI 26-47%]) vs. 91 (100% [95% CI 96-100%]) in the control and intervention groups, respectively (p = 0.0001).

Synthesis, characterization and optical properties of polymer-based ZnS nanocomposites.

Nanostructured polymer-semiconductor hybrid materials such as ZnS-poly(vinyl alcohol) (ZnS-PVA), ZnS-starch and ZnS-hydroxypropylmethyl cellulose (Zns-HPMC) are synthesized by a facile aqueous route. The obtained nanocomposites are characterized using various techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), UV/vis spectroscopy and photoluminescence (PL). XRD studies confirm the zinc blende phase of the nanocomposites and indicate the high purity of the samples. SEM studies indicate small nanoparticles clinging to the surface of a bigger particle. The Energy Dispersive Analysis by X-rays (EDAX) spectrum reveals that the elemental composition of the nanocomposites consists primarily of Zn:S. FTIR studies indicate that the polymer matrix is closely associated with ZnS nanoparticles. The large number of hydroxyl groups in the polymer matrix facilitates the complexation of metal ions. The absorption spectra of the specimens show a blue shift in the absorption edge. The spectrum reveals an absorption edge at 320, 310 and 325 nm, respectively. PL of nanocomposites shows broad peaks in the violet-blue region (420-450 nm). The emission intensity changes with the nature of capping agent. The PL intensity of ZnS-HPMC nanocomposites is found to be highest among the studied nanocomposites. The results clearly indicate that hydroxyl-functionalized HPMC is much more effective at nucleating and stabilizing colloidal ZnS nanoparticles in aqueous suspensions compared with PVA and starch.

Trends in human immunodeficiency virus seroprevalence in blood donors in northern Pakistan.

OBJECTIVE: To study trends in human immunodeficiency virus (HIV) seroprevalence in blood donors in northern Pakistan. STUDY DESIGN: Analysis of annual data from blood transfusion centre. PLACE AND DURATION OF STUDY: Data records from people who had donated blood at the Armed Forces Institute of Transfusion (AFIT) between 1998 and 2013 were retrieved and analysed. METHODS: All blood donations were tested for the presence of HIV antibodies using Abbott Inc's AxSYM from 1998 to 2006, and Abbott Inc's Architect 2000i with chemiluminescence microplate immunoassay from 2007 to 2013. RESULTS: Over the 16-year study period, 66 donors tested positive for HIV antibodies out of 626,413 donations (0.01%, i.e. 10 per 100,000 donations). From 1998 to 2006, 16 HIV-positive cases were detected out of 280,245 donations (0.0057%, i.e. 5.7 per 100,000 donations). However, from 2007 to 2013, 50 HIV-positive cases were detected out of 346,168 donations (0.0144%, i.e. 14 per 100,000 donations). The difference in HIV positivity between the two groups was found to be significant (0.0057% vs 0.0144%, χ(2) = 10.4, P = 0.008). CONCLUSION: A gradual and persistent increase in the number of HIV-positive cases among blood donors in northern Pakistan was seen over the study period. The HIV-positive cases reported one or more high-risk activities in the past which predisposed them to HIV infection.

Challenges in HbA1c Analysis and Reporting in Patients with Variant Hemoglobins.

Hemoglobin A1c (HbA(1)c) is a well-established indicator of mean glycemia. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA(1)c measurements. Variants of hemoglobin especially Hemoglobin E (HbE) is prevalent in South East Asia including Bangladesh. The objective of our study is to compare the HbA(1)c values measured on high performance liquid chromatography (HPLC) and Turbidimetric Inhibition Immunoassay (TINIA) in diabetic patients with variant hemoglobins including HbE. A total of 7595 diabetic patients receiving treatment at BIRDEM General Hospital were analyzed for HbA(1)c results within a period of two months from December 2013 to January 2014. Seventy two cases out of 7595 (0.95%) had either undetectable or below normal HbA(1)c levels (males-33 and females-39; ratio = 0.82:1) by HPLC method. In 34(0.45%) cases, HbA(1)c value was undetectable by HPLC method but was in the reportable range by TINIA method. In the other 38 (0.55%) cases, HbA(1)c levels were below the reportable range (<4%) by HPLC method but were in the normal or higher range by TINIA method. TINIA method did not agree with HPLC method on Bland Altman plot in the 38 cases with below normal HbA(1)c levels, [Mean bias -5.2(-9.3 to 1.0), 95% CI] but agreed very well [mean bias -0.21 (-0.84 to 0.42), y=1.1037+0.776X; r(2)=0.30, p<0.01] in controls. In control group mean MCV was 83.80±7.48 and in study group was 73.65±10.44. Alkaline electrophoresis confirmed the variant hemoglobin to be HbE. The fasting blood sugar levels of all the 72 cases correlated strongly with TINIA method (r(2) =0.75, p<0.0001) but not with HPLC (r = 0.24, p=0.13). In our regions where populations have a high prevalence of Hb variant, proper knowledge of hemoglobin variants which affect the measurements HbA(1)c level is essential. MCV of 80fl or below may serve as a rough guide to select samples that require analysis by TINIA method. Moreover, HPLC may be a convenient and inexpensive tool for screening of hemoglobinopathies especially among diabetic population in Bangladesh. It may therefore be helpful in improving management of complications related to both anaemia and iron overload.

Developing a prognostic model for localized Ewing sarcoma family of tumors: A single institutional experience of 224 cases treated with uniform chemotherapy protocol.

BACKGROUND: Data on patients with localized Ewing sarcoma family of tumors (ESFT) who have received a uniform chemotherapy protocol are minimal. METHODS: This is a single institutional review of patients with ESFT treated between June 2003 and November 2011. RESULTS: 224/374 (60%) patients with ESFT presented with localized disease; median age was 15 years (range: 0.1-55). Ninety-nine patients underwent surgery of which 50 received adjuvant radiotherapy; 80 patients received radical radiotherapy following neoadjuvant chemotherapy. At median follow-up of 40.2 months (range: 1.3-129), 5-year EFS, OS, and local-control-rate, were 36.8 ± 3.6%, 52.4 ± 4.3%, and 63 ± 4.3%, respectively. In multivariate analysis, tumor diameter > 8 cm (P = 0.03), symptom duration > 4 months (P = 0.04), and WBC > 11 × 10(9) /L (P = 0.003) predicted inferior EFS; spine/abdomino-pelvic primary (P = 0.009) and WBC > 11 × 10(9) /L (P = 0.003) predicted inferior OS. Tumor size > 8 cm (P = 0.03) and radical radiotherapy as local treatment (P = 0.01) predicted inferior local-control-rate. CONCLUSION: Prognostic hazard models for EFS and OS based on significant prognostic factors suggested that patients with combination of ESFT of spine/abdomino-pelvic region and baseline WBC > 11 × 10(9) /L had inferior OS (hazard ratio 4.44, P < 0.001) while patients with combination of ESFT with symptom duration > 4 months, tumor diameter > 8 m and baseline WBC > 11 × 10(9) /L had inferior EFS (hazard ratio 3.89, P = 0.002).

Genetic polymorphisms associated with sulphadoxine-pyrimethamine drug resistance among Plasmodium falciparum field isolates in malaria endemic areas of Assam.

BACKGROUND: The emergence of antimalarial drug resistance malaria parasite is widespread in North eastern region of India. During January 2012-December 2013, we conducted active surveillance for detection of antifolate resistance-associated genetic polymorphisms in Plasmodium falciparum malaria parasite from different malaria endemic areas of Assam. MATERIALS AND METHODS: A total of 281 field samples were collected from suspected malaria patients of which 106 malaria P. falciparum positive cases were detected in microscopic slide examination. A nested PCR was done for amplification of a 648 bp portion of the dhfr gene and 710 bp portion of the dhps gene. RESULTS: Mutation analysis revealed existence of three different haplotypes of the P. falciparum dhfr gene of which ANRNI was highly prevalent (90%). Triple mutant haplotypes AIRNI (N51I+C59R+S108N) of the dhfr gene associated with pyrimethamine resistance were prevalent in Chirang district of Assam. Whereas, dhps mutation study revealed that triple mutant haplotype AGEAA (S436A+A437G+K540E) associated with Sulphadoxine resistance was found among 26% of P. falciparum field isolates. However, P. falciparum dhfr-dhps two locus mutation analysis showed that there were a total of nine dhfr-dhps genotypes. CONCLUSION: It was noticed that 93.62% (88/94) isolates had mutations in the sequences of both enzymes, which is an indication of prevalence of high grade of Sulphadoxine - pyrimethamine resistance in P. falciparum malaria parasites in Assam.