bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remediation of intramacrophageal Shigella dysenteriae type 1 by probiotic lactobacilli isolated from human infants' stool samples
Authors: Trikha Radhika , Rishi Praveen , Tewari Rupinder 
Published: December 2024

Background & objectives:

Shigella dysenteriae is one of the most virulent pathogens causing bacillary dysentery and is responsible for high mortality in infants. To reduce the load of antibiotic therapy for treating shigellosis, this study was carried out to assess the ex vivo effect of novel probiotic lactobacilli, isolated from infant's stool samples, on killing S. dysenteriae type 1 residing in the rat macrophages.

Methods:
Stool samples from infants were collected, processed for the isolation of lactobacilli and screened for the probiotic attributes (acid tolerance, bile tolerance, ability to adhere intestinal cells and anti-S. dysenteriae activity). The effect of cell-free supernatant of lactobacilli on Shigella- infected macrophages in terms of phagocytic ability, extent of lipid peroxidation, nitrite, superoxide dismutase and glutathione levels was evaluated.

Results:
Based on the probiotic attributes, three lactobacilli were isolated from the stool samples of infants. Using classical and molecular tools, these isolates were identified as Lactobacillus pentosus, L. Paraplantarum and L. rhamnosus. All the three lactobacilli had the ability to kill intramacrophage S. dysentriae type 1. The anti-Shigella activity of the probiotic lactobacilli was attributed to increased antioxidative ability and decreased free radical production by the infected macrophages.

Interpretation & conclusions:
Probiotic cocktail of L. pentosus, L. paraplantarum and L. rhamnosus showed ex vivo killing of S. dysenteriae residing inside the rat macrophages significantly. This cocktail has the potential to be used as a natural alternative for treating S. dysenteriae infection, especially in infants, however, further studies need to be done to confirm these finding in vivo.
Interferon-γ-inducible protein-10 in chronic hepatitis C
Authors: Crisan Dana , Grigorescu Mircea Dan , Radu Corina , Suciu Alina , Grigorescu Mircea 
Published: December 2024

Background & objectives:
One of the multiple factors contributing to virological response in chronic hepatitis C (CHC) is interferon-gamma-inducible protein-10 (IP-10). Its level reflects the status of interferon-stimulated genes, which in turn is associated with virological response to antiviral therapy. The aim of this study was to evaluate the role of serum IP-10 levels on sustained virological response (SVR) and the association of this parameter with insulin resistance (IR) and liver histology.

Methods:
Two hundred and three consecutive biopsy proven CHC patients were included in the study. Serum levels of IP-10 were determined using ELISA method. IR was evaluated by homeostasis model assessment-IR (HOMA-IR). Histological features were assessed invasively by liver biopsy and noninvasively using FibroTest, ActiTest and SteatoTest. Predictive factors for SVR and their interrelations were assessed.

Results:
A cut-off value for IP-10 of 392 pg/ml was obtained to discriminate between responders and non-responders. SVR was obtained in 107 patients (52.70%). Area under the receiver operating characteristic curve for SVR was 0.875 with a sensitivity of 91.6 per cent, specificity 74.7 per cent, positive predictive value 80.3 per cent and negative predictive value 88.7 per cent. Higher values of IP-10 were associated with increasing stages of fibrosis (P<0.01) and higher grades of inflammation (P=0.02, P=0.07) assessed morphologically and noninvasively through FibroTest and ActiTest. Significant steatosis and IR were also associated with increased levels of IP-10 (P=0.01 and P=0.02). In multivariate analysis, IP-10 levels and fibrosis stages were independently associated with SVR.

Interpretation & conclusions:
Our findings showed that the assessment of serum IP-10 level could be a predictive factor for SVR and it was associated with fibrosis, necroinflammatory activity, significant steatosis and IR in patients with chronic HCV infection.
Effect of six-month use of oral contraceptive pills on plasminogen activator inhibitor-1 & factor VIII among women with polycystic ovary syndrome
Authors: Yousuf Syed Douhath , Ganie Mohammad Ashraf , Jeelani Samoon , Mudassar Syed , Shah Zaffar Amin , Zargar Mohammad Afzal , Amin Shajrul , Wani Imtiyaz Ahmad , Rashid Fouzia 
Published: December 2024

Background & objectives:
Polycystic ovary syndrome (PCOS) is an endocrinopathy warranting lifelong individualized management by lifestyle and pharmacological agents mainly oral contraceptive pills (OCPs). This study was aimed to report the impact of six-month OCP use on plasminogen activator inhibitor-1 (PAI-1) and factor VIII (FVIII) in women with PCOS.

Methods:
PCOS women diagnosed on the basis of Rotterdam 2003 criteria, either treated with OCPs (ethinyl estradiol-0.03 mg, levonorgestrel-0.15 mg) for a period of six months (n=40) or drug-naïve (n=42), were enrolled in this study. Blood was drawn to estimate glucose, insulin levels and lipid profile. Chemiluminescence immunoassays were used to measure hormones (LH, FSH, PRL, T4). Plasma levels of PAI-I and FVIII were measured by commercially available kits.

Results:
Menstrual regularity, Ferriman-Gallwey score and serum total testosterone significantly improved in the OCP group compared to drug-naïve group (P<0.01). No significant difference was observed in PAI-1 levels of the two groups; however, significant decrease in FVIII levels was observed in OCP group as compared to drug-naïve group. PAI-1 levels of OCP group correlated positively with blood glucose two hours, triglycerides and insulin two hours, while FVIII levels of OCP group correlated negatively with fasting insulin and homoeostatic model assessment-insulin resistance.

Interpretation & conclusions:
OCPs use has differential effect on pro-coagulant markers among women with PCOS. Well-designed, long-term, prospective, large-scale studies are prerequisite to elucidate the efficacy and safety of OCP in the treatment of PCOS.
Preclinical evaluation of hydrogel sealed fluropassivated indigenous vascular prosthesis
Authors: Unnikrishnan Madathipat , Umashankar P.R. , Viswanathan Sidharth , Savlania Ajay , Joseph Roy , Muraleedharan C.V. , Agrawal Vivek , Shenoy Sachin J. , Krishnan Lissy K. , Mohanan P.V. , Sabareeswaran A. 
Published: December 2024

Background & objectives:
Polyethylene terephthalate (PET) graft, designed and developed at our institute for vascular reconstruction, is porous to promote optimal incorporation and neointima formation, requiring pre-clotting or biomodification by sealing the pores before implantation. The objective of this study was to characterize, test and perform preclinical evaluation of hydrogel (alginate dialdehyde cross-linked gelatin) sealed fluoropassivated PET vascular prosthesis in pig model, so as to avoid pre-clotting, for its safety and efficacy before employing the indigenous and less expensive graft for clinical use.

Methods:
Hydrogel sealed, fluoropassivated PET vascular prosthesis were tested for haemocompatibility and toxicity followed by small animal toxicology tests and in vivo experiments in pigs receiving implantation at thoracic aorta. All 33 animals received test as well as control grafts with a plan for phased explantation at 2, 12 and 26 weeks. All animals underwent completion angiogram at the end of procedure as well as before graft explantation.

Results:
Haemocompatibility tests for haemolysis and toxicity tests showed no adverse events in tested mice and rabbits. Completion angiogram showed intact anastamosis and patent graft in each animal in post-operative period and at explantation. Gross and histopathological examination showed well-encapsulated grafts, clean glistening neointima and no evidence of thrombus in both test and control grafts.

Interpretation & conclusions:
Hydrogel sealed, fluoropassivated PET vascular prosthesis was found non-toxic, haemocompatible and remained patent in in vivo studies at planned intervals.
Socio-demographic determinants of out-of-pocket health expenditure in a rural area of Wardha district of Maharashtra, India
Authors: Loganathan Karthiyayini , Deshmukh Pradeep R. , Raut Abhishek V. 
Published: December 2024

Background & objectives:
In India, health expenditure accounts for less than 5 per cent of the Gross Domestic Product and the level of out-of-pocket (OOP) spending is 69.5 per cent of total health expenditures. OOP expenditure exacerbates poverty and has a negative impact on equity and can increase the risk of vulnerable groups slipping into poverty. This study was conducted to estimate the OOP expenditure on health and catastrophic health expenditure and their socio-demographic determinants in a rural area of Maharashtra, India.

Methods:
This was a prospective observational study involving monthly follow up visits, done in 180 households of three villages under a primary health centre in Wardha district, India.

Results:
Of the 180 families, 18.9 per cent had catastrophic health expenditure over a period of one year. The median total out-of-pocket health expenditure was ‘1105.00 with median medical expenditure being ‘863.85 and median non-medical health expenditure being ‘100.00. A total of 151 (83.9%) had enough money, 27 (15%) borrowed money and two (1.1%) of them sold assets. The significant correlates for the ratio of out-of-pocket health expenditure to total annual income of the family were the occupation of head of family, caste category and type of village. The significant correlate for catastrophic health expenditure was type of village.

Interpretation & conclusions:
Around one-fifth of the households had catastrophic health expenditure. People with no healthcare facility located in their village had higher odds of having catastrophic health expenditure. Private providers were preferred for the treatment of acute illnesses and medical college hospitals for hospitalization.
Prenatal diagnosis of steroid 21-hydroxylase-deficient congenital adrenal hyperplasia
Authors: Dubey Sudhisha , Tardy Veronique , Chowdhury Madhumita Roy , Gupta Neerja , Jain Vandana , Deka Deepika , Sharma Pankaj , Morel Yves , Kabra Madhulika 
Published: December 2024

Background & objectives:
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder with a wide range of clinical manifestations. The disease is attributed to mutations in CYP21A2 gene encoding 21-hydroxylase enzyme. In view of severe phenotype in salt-losing cases, issues related to genital ambiguity in girls and precocity in boys, most families opt for prenatal testing and termination of affected foetus. CAH can be diagnosed in utero through direct molecular analysis of CYP21A2 gene, using DNA extracted from foetal tissues or cells obtained from chorionic villus sampling or amniocentesis. The objective of this study was to evaluate the feasibility and accuracy of prenatal diagnosis (PND) using sequencing and multiplex ligation probe amplification (MLPA) methods in families at risk for CAH.

Methods:
Fifteen pregnant women at risk of having an affected offspring with CAH were included in this study. Ten families had previous affected children with salt-wasting/simple virilising form of CAH and five families did not have live children but had a high index of suspicion for CAH in previous children based on history or records. Mutation analysis was carried out by Sanger sequencing and MLPA method.

Results:
Seven different mutations were identified in 15 families. Deletions and I2g mutation were the most common. Of the 15 foetuses analyzed, nine were unaffected while six were affected. Unaffected foetuses were delivered, they were clinically normal and their genotype was found to be concordant to the prenatal report. All except two families reported in the second trimester. None of the couples opted for prenatal treatment.

Interpretation & conclusions:
Our preliminary findings show that PND by direct mutation analysis along with MLPA is a feasible strategy that can be offered to families at risk.
Identification of a novel homozygous mutation in transmembrane channel like 1 (TMC1) gene, one of the second-tier hearing loss genes after GJB2 in India
Authors: Singh Pawan Kumar , Ghosh Manju , Sharma Shipra , Shastri Shivaram , Gupta Neerja , Chowdhury Madhumita Roy , Anand Anuranjan , Kabra Madhulika 
Published: December 2024

Background & objectives:
Hearing impairment is a common and heterogeneous sensory disorder in humans. Among about 90 genes, which are known to be associated with hearing impairment, mutations in the GJB2 (gap junction protein beta 2) gene are the most prevalent in individuals with hereditary hearing loss. Contribution of the other deafness-causing genes is relatively poorly understood. Here, we present our findings on two families with transmembrane channel like 1 (TMC1) gene variants of the 47 families with nonsyndromic hearing loss (NSHL) studied.

Methods:
Forty seven families including 26 consanguineous families with at least two hearing impaired children and one normal hearing child and 21 non-consanguineous families having at least three hearing impaired children and one normal hearing child were enrolled for this study. Genetic linkage studies were carried out in 41 families that were GJB2 (Connexin 26) negative. Seven polymorphic short tandem repeat markers at the DFNB7/11 locus were studied employing fluorescently labelled markers.

Results:
A novel homozygous missense mutation c.1283C>A (p.Ala428Asp) was identified co-segregating with hearing loss. This change results in substitution of a highly conserved polar alanine to a charged aspartic acid and is predicted to be deleterious. In addition, a previously reported nonsense mutation, p.R34X in TMC1, was found.

Interpretation & conclusions:
While mutations in TMC1 are not as common a cause of NSHL as those in GJB2, TMC1 should be considered for diagnostic investigations in cases of NSHL in GJB2-negative families.
Mutations in OTOF, CLDN14 & SLC26A4 genes as major causes of hearing impairment in Dhadkai village, Jammu & Kashmir, India
Authors: Pandey Nishtha , Rashid Tabassum , Jalvi Rajeev , Sharma Meenakshi , Rangasayee Raghunath , Andrabi Khurshid Iqbal , Anand Anuranjan 
Published: December 2024

Background & objectives:
A high incidence of hearing impairment is reported from the village of Dhadkai in the State of Jammu and Kashmir, India. Prevalence of endogamy in this community suggested a common genetic basis for the disorder. A genetic study was undertaken to ascertain the basis for the high incidence of hearing impairment in this region.

Methods:
In a two-step approach to identify the causative mutation/s, a whole-genome-based linkage analysis of an extended family of 45 members was carried out, which included 23 affected and 22 unaffected members. Mutational analysis for the candidate deafness genes helped reveal causative mutations in the family. In addition, seven deafness-causing genes, Cx26, SLC26A4, CLDN14, TMPRSS3, TMC1, TMIE and USH1C, were analyzed in smaller families with hearing impairment.

Results:
In the 45-member extended family, the critical chromosomal region mapped to 2p24-p22. The c.2122C>T (p.R708X) mutation in OTOF in 2p24-p22was identified as being the causal change. Linkage to 2p24-p22 locus was not observed in a particular branch of this extended family. Analysis of seven known deafness-causing genes in this branch revealed a mutation, c.254T>A (p.V85D), in CLDN14. Among seven small families unrelated to the 45-member extended family, hearing loss was attributable to p.R708X in OTOF in three families and to p.V85D in CLDN14 in one family; a new mutation c.1668T>A (p.Y556X) SLC26A4 was identified in two families and the causative change could not be identified in one family.

Interpretation & conclusions:
This study suggested considerable genetic heterogeneity in the causation of hearing loss in Dhadkai. Recessive mutations were observed in at least three genes causing hearing loss: OTOF (p.R708X), SLC26A4 (p.Y556X) and CLDN14 (p.V85D). Mutation p.R708X appeared to be the major cause of hearing impairment in Dhadkai.
Cost of delivering secondary-level health care services through public sector district hospitals in India
Authors: Prinja Shankar , Balasubramanian Deepak , Jeet Gursimer , Verma Ramesh , Kumar Dinesh , Bahuguna Pankaj , Kaur Manmeet , Kumar Rajesh 
Published: December 2024

Background & objectives:
Despite an impetus for strengthening public sector district hospitals for provision of secondary health care in India, there is lack of robust evidence on cost of services provided through these district hospitals. In this study, an attempt was made to determine the unit cost of an outpatient visit consultation, inpatient bed-day of hospitalization, surgical procedure and overall per-capita cost of providing secondary care through district hospitals.

Methods:
Economic costing of five randomly selected district hospitals in two north Indian States - Haryana and Punjab, was undertaken. Cost analysis was done using a health system perspective and employing bottom-up costing methodology. Quantity of all resources - capital or recurrent, used for delivering services was measured and valued. Median unit costs were estimated along with their 95 per cent confidence intervals. Sensitivity analysis was undertaken to assess the effect of uncertainties in prices and other assumptions; and to generalize the findings for Indian set-up.

Results:
The overall annual cost of delivering secondary-level health care services through a public sector district hospital in north India was

JOURNAL/ijmer/04.03/02223309-201746030-00010/math_10MM1/v/2022-09-30T185254Z/r/image-tiff

11,44,13,282 [US Dollars (USD) 2,103,185]. Human resources accounted for 53 per cent of the overall cost. The unit cost of an inpatient bed-day, surgical procedure and outpatient consultation was

JOURNAL/ijmer/04.03/02223309-201746030-00010/math_10MM2/v/2022-09-30T185254Z/r/image-tiff

844 (USD 15.5), i; 3481 (USD 64) and

JOURNAL/ijmer/04.03/02223309-201746030-00010/math_10MM3/v/2022-09-30T185254Z/r/image-tiff

170 (USD 3.1), respectively. With the current set of resource allocation, per-capita cost of providing health care through district hospitals in north India was

JOURNAL/ijmer/04.03/02223309-201746030-00010/math_10MM4/v/2022-09-30T185254Z/r/image-tiff

139 (USD 2.5).

Interpretation & conclusions:
The estimates obtained in our study can be used for Fiscal planning of scaling up secondary-level health services. Further, these may be particularly useful for future research such as benefit-incidence analysis, cost-effectiveness analysis and national health accounts including disease-specific accounts in India.
Pyrazinamide Resistance: A Major Cause of Switching Shorter to Longer Bedaquiline-based Regimens in Multidrug-resistant Tuberculosis Patients
Authors: Putra Oki Nugraha , Indah Nur , Purnamasari Telly , Larasanti Adi 
Published: December 2024

Background:
All-oral regimens, including bedaquiline, are now standard in shorter treatment regimens (STRs) for multidrug-resistant tuberculosis (MDR-TB). Resistance or intolerance to drugs in STR often necessitates a switch to longer treatment regimens (LTRs). This study aims to identify the factors associated with this transition in MDR-TB patients.

Methods:
We conducted a retrospective analysis of medical records from MDR-TB patients treated with STR at Haji Hospital, Surabaya, between January 2022 and January 2023. Data on drug-resistance profiles, determined by drug-susceptibility testing (DST), and line probe assay, as well as adverse effects, were collected.

Results:
Among 20 eligible patients, 8 (40.0%) switched from STR to LTR within the first 4 months. Resistance was observed in 62.5% of these patients for pyrazinamide, 25.0% for high-dose isoniazid, and 12.5% for levofloxacin. The overall prevalence of pyrazinamide resistance was 25.0%. A history of prior antitubercular treatment was significantly associated with pyrazinamide resistance (P = 0.015; RR – 16.000; confidence interval 95% 1.274–200.917).

Conclusion:
Pyrazinamide resistance is a major factor for switching from STR to LTR in MDR-TB patients, particularly among those with previous TB treatment. Rapid DST for pyrazinamide is essential for the early identification of resistance and timely adjustments to treatment regimens.
A Cost-effective Breath-hold Coaching Camera System for Patients Undergoing External Beam Radiotherapy
Authors: Mehta Akash , Horgan Emma , Ramachandran Prabhakar , Noble Christopher 
Published: December 2024

Purpose:
Organ motion can significantly affect the accurate delivery of radiation doses to the tumor, particularly for sites such as the breast, lung, abdomen, and pelvis. Managing this motion during treatment is crucial. One strategy employed to manage motion induced from respiration is breath-hold (BH), which enhances the geometric precision of dose delivery. Our institute is transitioning to using the ExacTrac Dynamic system to facilitate patient BH using surface-guided cameras. Only 20% of our linacs are equipped with surface guidance capabilities, and due to a high patient stereotactic throughput, the ability to perform in-bunker coaching for BH patients within the bunker is limited. To address this challenge, a time-of-flight camera (ToF) was developed to coach radiotherapy patients undergoing BH procedures, allowing them to gain confidence in the process outside of the bunker and before treatment.

Methods:
The camera underwent testing for absolute and relative accuracy, responsiveness under various environmental conditions, and comparison with the Elekta Active Breathing Coordinator (ABC) to establish correlation and testing on volunteers independently to assess usability.

Results:
The results showed that the absolute distance measured by the camera was nonlinear due to square light modulation, which was retrospectively corrected. Relative accuracy was tested with a QUASAR motion phantom, with results agreeing to within ± 2 mm. The camera response was found to be unaffected by changes in lighting or temperature, though it overresponded under extreme temperatures. The comparison with the Elekta ABC system yielded comparable results between lung volume and changes in surface distance during BH. All volunteers successfully followed instructions and maintained BH within ± 1 mm tolerance.

Conclusions:
This study demonstrates the feasibility of using a cost-effective ToF camera to coach patients before imaging/treatment, saving valuable LINAC linac and imaging system time.