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1.
J Perinat Med ; 52(5): 520-529, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38709224

ABSTRACT

OBJECTIVES: With the availability of Next Generation Sequencing (NGS) diagnosis of genetic disorders has improved significantly. Its use is also applicable to ascertain diagnosis and management in a perinatal setting. The study aims to detect the genetic aetiology of various congenital structural and functional defects using NGS technology in the reproductive cohort at a tertiary centre. The secondary objective is to address challenges in the interpretation of variants. METHODS: This was a retrospective study of couples who underwent exome sequencing (Mono-testing proband only or Duo-testing parents only or Trio-testing proband and parents) for suspected single gene disorders between years 2020-2022 at a tertiary care perinatal center in the South India. American College of Medical Genetics (ACMG) guidelines were followed to classify the pathogenicity of the variants identified by exome sequencing. RESULTS: The overall diagnostic yield as defined by pathogenic/likely pathogenic variants obtained was (23/43) 53.4 %. The individual subsets have the following diagnostic yield viz., Mono 5/6 (83 %); Carrier 16/32 (50 %); Trio 2/5 (40 %). Diagnostic yield was significantly higher in consanguineous couples. However, miscarriage history, and organ system involvement did not have a significant effect on the diagnostic yield. Prenatal diagnosis was offered for seven patients based on the exome result. One fetus was confirmed with a compound heterozygous pathogenic variant. CONCLUSIONS: Diagnostic yield of exome sequencing in our cohort was 53 %. The detection of pathogenic variants was maximum in those cases undergoing Mono exome sequencing. In places where there is a high prevalence of consanguinity and endogamy, NGS may be offered as first line test in the context of prenatal diagnosis.


Subject(s)
Exome Sequencing , Prenatal Diagnosis , Tertiary Care Centers , Humans , Retrospective Studies , Female , India/epidemiology , Tertiary Care Centers/statistics & numerical data , Exome Sequencing/methods , Pregnancy , Prenatal Diagnosis/methods , Prenatal Diagnosis/statistics & numerical data , Male , Adult , High-Throughput Nucleotide Sequencing/methods , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/epidemiology , Genetic Testing/methods
3.
Public Health ; 227: 176-186, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38232566

ABSTRACT

OBJECTIVE: India is the third-largest tobacco manufacturer and its use in India is characterised by a high prevalence of smoking and smokeless (sl) tobacco use. This results in 1 million deaths per year in the country. Given the high burden of tobacco use, this study examines the regional variations and socio-economic correlates of tobacco use in India. METHODS: National Family Health Survey- 5 (2019-2020) have been analysed for the purpose of the study. A sample of 101,839 males aged 15-54 years was included in this study. Primary outcomes of tobacco use were categorised into smoking, smokeless and dual use of smoking and smokeless tobacco use. Bivariate analysis and decomposition analysis was done to study the socio-economic inequality. RESULTS: The prevalence of tobacco use among males in India is around 41 percent. As indicated by the results of the logistics regression, age is positively related to smoking among males. Males aged 45-54 years are 2.5 (95 % concentration index [CI]:2.30-2.63) times probable to smoke, 1.4 (95% CI: 1.30-1.47) times probable of smokeless tobacco consumption and 2.2 (95% CI: 2.10-2.35) times more prone to using both types of substances compared to the younger age group. Males who are widower use smokeless 1.69 times (95% CI: 1.44-1.99) higher with reference to unmarried males. Males belonging to Scheduled tribes are 1.2 (95% CI: 1.13-1.25) times more likely to smoke, 1.3 (95% CI: 1.24-1.37) times more likely to use smokeless substances and 1.4 (95% CI: 1.33-1.47) times more likely to have dual use of tobacco than other social groups. Manual workers (both skilled are unskilled) are likely to smoke (odds ratio [OR] = 1.1, 95% CI: 1.02-1.11), use smokeless tobacco (OR = 1.3, 95% CI: 1.23-1.34) and have dual use of tobacco (OR = 1.29, 95% CI: 1.24-1.34) more than that of other categories. The decomposition of the concentration index shows a significant contribution from factors like a no education, ST/SC caste and wealth index. Among the states and union territories, the prevalence of tobacco is high in West Bengal, Tripura, Mizoram, Manipur, Meghalaya and Sikkim. CONCLUSION: This study is useful for informing target-based prevention policies since it helps in highlighting regions, socio-economic and demographic groups especially vulnerable to tobacco addiction. In India, males from poorer and vulnerable socio-economic backgrounds are more likely to use tobacco. State wise, the eastern zone starting from West Bengal to the North-Eastern states have higher tobacco use than the rest of the country. There is an urgent need to frame policies for controlling the use of tobacco especially among high-risk groups.


Subject(s)
Tobacco Use Disorder , Tobacco, Smokeless , Male , Humans , Socioeconomic Factors , India/epidemiology , Tobacco Use Disorder/epidemiology , Prevalence , Smoking/epidemiology
4.
Water Sci Technol ; 88(9): 2284-2296, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37966183

ABSTRACT

Spatial and temporal variations of the water table could be explained by the one-dimensional Boussinesq equation by incorporating the variables of evapotranspiration and groundwater recharge with appropriate initial and boundary conditions. In this study, the stream-aquifer interaction has been investigated through a numerical example model with the implementations of Galerkin's method-based Finite Element Solution (FES), Hybrid Finite Analytic Solution (HFAS), Fully Implicit Finite Difference Solution (FIFDS) of one-dimensional nonlinear Boussinesq equation, and analytical solutions of the Boussinesq equation linearized by Baumann's transformation (AS I) as well as linearized by Werner's transformation (AS II). Considering HFAS as the benchmark solution, it was observed that in both recharging and discharging aquifers, water table profiles at 1 day and 5 days as obtained from FES followed by FIFDS were observed quite close to HFAS. Based on L2 and Tchebycheff norms, FES and FIFDS were ranked in first and second place, respectively. L2 and Tchebycheff norms could not consistently establish the performance ranking of analytical solutions but their performance ranking was certainly below the numerical solutions. The performance ranking of analytical solutions could not consistently be established using the L2 and Tchebycheff norms, but it was certainly below the numerical solutions.


Subject(s)
Groundwater , Rivers , Water Movements , Models, Theoretical , Benchmarking
5.
Anaesth Intensive Care ; 51(6): 408-421, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37786341

ABSTRACT

Regional anaesthesia is an essential tool in the armamentarium for paediatric anaesthesia. While largely safe and effective, a range of serious yet preventable adverse events can occur. Incidence and risk factors have been described, but few detailed case series exist relating to paediatric regional anaesthesia. Across Australia and New Zealand, a web-based anaesthesia incident reporting system enables voluntary reporting of detailed anaesthesia-related events in adults and children. From this database, all reports involving paediatric regional anaesthesia (age less than 17 years) were retrieved. Perioperative events and their outcomes were reviewed and analysed. When offered, the reported contributing or alleviating factors relating to the case and its management were noted. This paper provides a summary of these reports alongside an evidence review to support safe practice. Of 8000 reported incidents, 26 related to paediatric regional anaesthesia were identified. There were no deaths or reports of permanent harm. Nine reports of local anaesthetic systemic toxicity were included, seven equipment and technical issues, six errors in which regional anaesthesia made an indirect contribution and four logistical and communication issues. Most incidents involved single-shot techniques or a neuraxial approach. Common themes included variable local anaesthetic dosing, cognitive overload, inadequate preparation and communication breakdown. Neonates, infants and medically complex children were disproportionately represented, highlighting their inherent risk profile. A range of preventable incidents are reported relating to patient, systems and human factors, demonstrating several areas for improvement. Risk stratification, application of existing dosing and administration guidelines, and effective teamwork and communication are encouraged to ensure safe regional anaesthesia in the paediatric population.


Subject(s)
Anesthesia, Conduction , Anesthesiology , Infant , Infant, Newborn , Adult , Child , Humans , Adolescent , Anesthetics, Local , Anesthesia, Conduction/adverse effects , Risk Management , Anesthesia, Local
6.
J Pharm Bioallied Sci ; 15(Suppl 1): S230-S234, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37654260

ABSTRACT

In forensic, odontologic, genetic, and anthropological aspects, odontometric and osteologic features have long been a valuable source. The goal of this research was to correlate both the osteologic and odontometric characteristics to determine the most accurate approach for determining gender. A retrospective study involving 1000 adults, with equal gender distribution, was carried out utilizing digital panoramic radiography. The archives were searched for radiographic images of the subjects that were procured for the various procedures that ranged from implantations to rehabilitations. The measurement process was carried out with Image-Pro. There was a noticeable gender difference in the mesodistal breadth, which ranged from 17 to 47. Asymmetry of the lower jaw was considerable in both genders, as was gender variance in osseologic characteristics including ramus diameter and gonial angle. The two groups of attributes exhibited a substantial positive predictive value and thus can be used indetermining gender.

7.
J Pharm Bioallied Sci ; 15(Suppl 1): S239-S243, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37654335

ABSTRACT

Reasons for the failed endodontic teeth which had an extensive restoration can be attributed to the multiple materials that were used in it. Various post-core materials that are commonly used are compared for fracture resistance in the current study. Fourty maxillary incisors that needed root canal therapy were allocated into four groups of 10 each. Using adhesive resin cement, teeth were repaired in three experimental groups with ceramic fiber post, glass post, and stainless steel post. All these posts with composite post and core. Samples that still had their coronal structure were considered as controls that were without any post-cores. Every sample was ready for the best abutment preparation. Using the universal testing machine, all the specimens were examined for the compressive strength at 130° until fracture was experienced. The data for the force levels at which the fracture occurred were noted and compared for significance using analysis of variance (ANOVA), keeping P < 0.05 as significant. The fracture resistance values were significantly variable among all the groups, with P < 0.05. The stainless steel post exhibited the highest strength before it succumbed to the fracture. The glass posts showed better restorability and were esthetically acceptable. The least fracture resistance was demonstrated by teeth that had no post-core, highlighting the necessity of strengthening the tooth. Among all the experimental groups, the one that demonstrated the highest fracture resistance was composite core and steel posts.

8.
Cureus ; 15(8): e43698, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37724213

ABSTRACT

Introduction An intertrochanteric (IT) femur fracture is an extra-capsular fracture between greater and lesser trochanters. Unstable IT fractures are those where there is poor contact between fracture fragments (especially medial and posterior cortices), comminution, and fracture pattern, such that the weight-bearing forces tend to displace the fracture further or a reverse oblique type. Proximal femoral nailing (PFN) is one of the modalities for proximal femoral fractures. A newer modality for proximal femoral fracture is PFNA2, i.e., PFN anti-rotation, which makes use of a helical blade for a better compaction of bone. Both nail designs (PFN and PFNA2) are available in short and long sizes (so a total of four variants). Only a few studies have compared the treatment of IT femur fracture concerning fracture geometry, design, and length using either of the two nail types. In our study, we assessed the surgical and functional outcomes of PFN and PFNA2. Materials and methods This prospective observational study was carried out on 30 patients who had sustained IT fractures of the femur. All cases of IT femur fractures more than 18 years of age, closed injuries, and the patients who consented to participate in this program were included in the study. All open injuries, the patients who refused to participate in this program, patients who have associated injuries, patients with a subtrochanteric femur fracture, and patients with less than six months of follow-up were excluded. The patients were randomized into two types of implant groups. All patients were operated with a standard protocol. The study was conducted for 18 months from February 2021 to August 2022. The results were analyzed (of all four variants) by comparing patient demographics, implant size, implant type, locking methods, union time, and other parameters. Results Most of the patients were operated on with a 10 mm nail diameter (17/30 patients), 380 mm length (long-nail group) (five/11 patients), and 250 mm length (short-nail group). With the use of PFNA2, the overall duration of hospital stay was less. The overall operative time (incision to wound closure) with the use of the short PFNA2 was lesser than that with the use of other designs due to the use of the zig for distal screws. The use of a distal dynamic locking screw in a majority of the patients can get better compression at the fracture site once the patient starts weight bearing and decrease the chances of the Z-effect, reverse Z-effect, screw back-out, and screw cut-out. The union time was nearly the same in the majority of the patients, with an early union seen with the use of PFNA2 nails. The overall modified Harris hip score (HHS) at the final follow-up was nearly the same with slightly better results with the use of PFNA2. Conclusions PFNA2 is the implant of choice in elderly patients with osteoporotic bone. It has less operative time, which is required in such patients with medical comorbidities; hence, it has marginal superiority over PFN. Short-nail design results in less operative time and less blood loss.

9.
Front Dent ; 20: 4, 2023.
Article in English | MEDLINE | ID: mdl-37312826

ABSTRACT

Objectives: The purpose of this randomized parallel clinical trial was to assess and compare the efficacy of 97% Aloe Vera (AV) gel and 94.7% AV juice against an active control (0.05% Clobetasol Propionate) in the treatment of oral lichen planus (OLP). Materials and Methods : Age and sex matched patients with histologically proven OLP were divided into two groups. One group received 97% AV gel for topical application and 10ml 94.7% AV juice to consume twice daily. The active control group received topical 0.05% Clobetasol Propionate ointment twice daily. Treatment lasted two months followed by four months of observation. Monthly evaluation of various clinical features of OLP was done using the OLP disease scoring criteria. Burning sensation was evaluated using Visual Analog Scale (VAS). Mann Whitney-U (followed by Bonferroni adjustment) and Wilcoxon's signed-rank tests were used for intergroup and intragroup comparisons, respectively. Interclass correlation-coefficient test was applied to assess the intra-observer variation (P<0.05). Results: In total, 41 females and 19 males participated in this study. The most common site was the buccal mucosa followed by the gingivobuccal vestibule. The reticular variant was most frequently encountered. Wilcoxon's signed-rank test showed significant differences in both groups between baseline and end-of-treatment for VAS, site-score, reticular/plaque/papular score, erosive/atrophic score and OLP disease score (P<0.05). Mann-Whitney revealed significant difference between both groups in the 2nd, 3rd and 4th months (P<0.0071). Conclusion: Clobetasol Propionate is more effective for OLP management but in our study AV proved to be a safe treatment alternative for OLP management.

10.
Asian J Transfus Sci ; 17(1): 121-124, 2023.
Article in English | MEDLINE | ID: mdl-37188012

ABSTRACT

BACKGROUND: Sickle cell disease (SCD) patients may develop multiple alloantibodies that pose problem in finding compatible blood for transfusion and require crossmatching with large number of blood. AIM: The aim of the present study was to find compatible blood with reduced cost by adopting a conservative approach. MATERIALS AND METHODS: A step-by-step approach using tube technique, antibodies in original serum, and the saved test supernatant (TS) in search of compatible blood for transfusion purposes. RESULTS: 32 years SCD patient grouped A with multiple antibodies required transfusion. A total of 641 red blood cell (RBC) units of groups A and O were crossmatched using serum and the TS by tube method. Of 138 units tested using the serum at 4°C, 124 units showed direct agglutination in the saline phase and the remaining 14 units were processed through low ionic strength solution (LISS)-IAT, of which 2 units were compatible even by the gel-IgG-card method. The TS, saved from the tests on serum, was used in an identical manner as that of the serum to screen additional 503 units by saline tube method at 4°C units showed direct agglutination of the RBCs of 428 units, hence were removed from inventory for this patient. The remaining 75 units were tested by the LISS-IAT-tube method at 37°C, of which 8 units were found compatible but only 2 units were clear compatible by the gel-IgG-card method. As such, 4 units compatible by the sensitive gel-IgG-card method were issued for transfusion purposes. CONCLUSION: The new approach on using the saved TS consumed less of the patient's blood specimen, and the use of the tube method in screening and eliminating a large chunk of incompatible blood units has proved economical if compared with the use of the only gel-IgG-cards device in the entire maneuvering.

11.
Pediatr Blood Cancer ; 70(7): e30336, 2023 07.
Article in English | MEDLINE | ID: mdl-37057741

ABSTRACT

BACKGROUND: Recent studies suggest that cerebral revascularization surgery may be a safe and effective therapy to reduce stroke risk in patients with sickle cell disease and moyamoya syndrome (SCD-MMS). METHODS: We performed a multicenter, retrospective study of children with SCD-MMS treated with conservative management alone (conservative group)-chronic blood transfusion and/or hydroxyurea-versus conservative management plus surgical revascularization (surgery group). We monitored cerebrovascular event (CVE) rates-a composite of strokes and transient ischemic attacks. Multivariable logistic regression was used to compare CVE occurrence and multivariable Poisson regression was used to compare incidence rates between groups. Covariates in multivariable models included age at treatment start, age at moyamoya diagnosis, antiplatelet use, CVE history, and the risk period length. RESULTS: We identified 141 patients with SCD-MMS, 78 (55.3%) in the surgery group and 63 (44.7%) in the conservative group. Compared with the conservative group, preoperatively the surgery group had a younger age at moyamoya diagnosis, worse baseline modified Rankin scale scores, and increased prevalence of CVEs. Despite more severe pretreatment disease, the surgery group had reduced odds of new CVEs after surgery (odds ratio = 0.27, 95% confidence interval [CI] = 0.08-0.94, p = .040). Furthermore, comparing surgery group patients during presurgical versus postsurgical periods, CVEs odds were significantly reduced after surgery (odds ratio = 0.22, 95% CI = 0.08-0.58, p = .002). CONCLUSIONS: When added to conservative management, cerebral revascularization surgery appears to reduce the risk of CVEs in patients with SCD-MMS. A prospective study will be needed to validate these findings.


Subject(s)
Anemia, Sickle Cell , Cerebral Revascularization , Moyamoya Disease , Stroke , Humans , Child , Retrospective Studies , Moyamoya Disease/etiology , Cerebral Revascularization/adverse effects , Cerebral Revascularization/methods , Prospective Studies , Stroke/etiology , Anemia, Sickle Cell/complications , Treatment Outcome
12.
Asian J Transfus Sci ; 17(2): 273-275, 2023.
Article in English | MEDLINE | ID: mdl-38274962

ABSTRACT

A positive direct antiglobulin test (DAT) is of diagnostic feature for the patient with autoimmune hemolytic anemia (AIHA). However, on rare occasions, for obscure reasons, it is found among healthy blood donors. The present report is aimed to elucidate serological and immunological characteristics of such autoantibody in a healthy donor aged 62 years found with positive DAT. There was no history of Leishmaniasis, nor having a significant illness. His red blood cells (RBCs) showed incompatible cross-match results with every recipient tested in the antiglobulin phase. He was found to be DAT+. As his plasma had very little presence of autoantibody, hence was augmented by elution from his in vivo sensitized RBCs for the study. Autoantibody with immunoglobulin IgG showed predominant specificity of anti-Ce. It is certainly a rare case of autoantibody to RhCe compound antigen yet being innocuous in a healthy blood donor with a positive DAT.

13.
Cells ; 11(7)2022 04 02.
Article in English | MEDLINE | ID: mdl-35406765

ABSTRACT

The global burden of malaria and toxoplasmosis has been limited by the use of efficacious anti-parasitic agents, however, emerging resistance in Plasmodium species and Toxoplasma gondii threatens disease control worldwide, implying that new agents/therapeutic targets are urgently needed. Nuclear localization signal (NLS)-dependent transport into the nucleus, mediated by members of the importin (IMP) superfamily of nuclear transporters, has shown potential as a target for intervention to limit viral infection. Here, we show for the first time that IMPα from P. falciparum and T. gondii have promise as targets for small molecule inhibitors. We use high-throughput screening to identify agents able to inhibit P. falciparum IMPα binding to a P. falciparum NLS, identifying a number of compounds that inhibit binding in the µM-nM range, through direct binding to P. falciparum IMPα, as shown in thermostability assays. Of these, BAY 11-7085 is shown to be a specific inhibitor of P. falciparum IMPα-NLS recognition. Importantly, a number of the inhibitors limited growth by both P. falciparum and T. gondii. The results strengthen the hypothesis that apicomplexan IMPα proteins have potential as therapeutic targets to aid in identifying novel agents for two important, yet neglected, parasitic diseases.


Subject(s)
Plasmodium falciparum , alpha Karyopherins , High-Throughput Screening Assays , Nuclear Localization Signals/metabolism , Plasmodium falciparum/drug effects , Plasmodium falciparum/metabolism , Protein Binding , alpha Karyopherins/antagonists & inhibitors
14.
J Appl Microbiol ; 132(4): 3142-3154, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35119711

ABSTRACT

AIM: The main aim of the present study was to develop nanotechnology-based solutions for the management of a fungus, Phytophthora parasitica causing gummosis in citrus. METHODS AND RESULTS: Biogenic copper nanoparticles (CuONPs) were synthesized using two different biocontrol agents, Pseudomonas fluorescens and Trichoderma viride and characterized using different analytical techniques. Furthermore, in vitro (at the concentrations of 10, 15, 30, 50, 70, 100 and 150 mg/L) and in vivo (at the concentration of 100 mg/L) activities of these nanoparticles were evaluated for their antifungal efficacy against P. parasitica. The results obtained confirmed the synthesis of irregular-shaped CuONPs having a size in the range 40-100 nm in case of P. fluorescens, whereas, spherical CuONPs in the size range 20-80 were recorded in case of T. viride. As far as the in vitro antifungal efficacies of both these CuONPs is concerned, the maximum percent growth inhibition was observed in case of CuONPs synthesized from T. viride compared to CuONPs from P. fluorescens. However, in case of in vivo antifungal efficacies, CuONPs synthesized from T. viride showed the activity significantly higher than the conventionally used Bordeaux mixture. CONCLUSIONS: It can be concluded that biosynthesized CuONPs can be effectively used as a potential fungicide against P. parasitica. SIGNIFICANCE AND IMPACT OF THE STUDY: The application of nanoparticles having antifungal activities can be used as alternative fungicides to the conventional chemical fungicides. It has the potential to revolutionize the existing management strategies available for plant pathogenic fungi.


Subject(s)
Citrus , Metal Nanoparticles , Nanoparticles , Phytophthora , Copper/chemistry , Copper/pharmacology , Green Chemistry Technology/methods , Metal Nanoparticles/chemistry , Oxides
15.
Int J Radiat Oncol Biol Phys ; 112(1): 158-166, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34348176

ABSTRACT

PURPOSE: For curative treatment of Hodgkin lymphoma, radiation therapy benefit must be weighed against toxicity. Although more costly, proton radiation therapy reduces dose to healthy tissue, potentially improving the therapeutic ratio compared with photons. We sought to determine the cost-effectiveness of proton versus photon therapy for mediastinal Hodgkin lymphoma (MHL) based on reduced heart disease. METHODS AND MATERIALS: Our model approach was 2-fold: (1) Use patient-level dosimetric information for a cost-effectiveness analysis using a Markov cohort model. (2) Use population-based data to develop guidelines for policymakers to determine thresholds of proton therapy favorability for a given photon dose. The HD14 trial informed relapse risk; coronary heart disease risk was informed by the Framingham risk calculator modified by the mean heart dose (MHD) from radiation. Sensitivity analyses assessed model robustness and identified the most influential model assumptions. A 30-year-old adult with MHL was the base case using 30.6-Gy proton therapy versus photon intensity modulated radiation therapy. RESULTS: Proton therapy was not cost-effective in the base case for male ($129,000/ quality-adjusted life years [QALYs]) or female patients ($196,000/QALY). A 5-Gy MHD decrease was associated with proton therapy incremental cost-effectiveness ratio <$100,000/QALY in 40% of scenarios. The hazard ratio associating MHD and heart disease was the most influential clinical parameter. CONCLUSIONS: Proton therapy may be cost-effective a select minority of patients with MHL based on age, sex, and MHD reduction. We present guidance for clinicians using MHD to aid decision-making for radiation therapy modality.


Subject(s)
Hodgkin Disease , Proton Therapy , Adult , Cost-Benefit Analysis , Female , Hodgkin Disease/radiotherapy , Humans , Male , Neoplasm Recurrence, Local/etiology , Proton Therapy/adverse effects , Proton Therapy/methods , Quality-Adjusted Life Years
16.
Transfus Med Hemother ; 48(4): 240-243, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34539318

ABSTRACT

INTRODUCTION: The identification of alloantibodies to high-frequency antigens (HFA) and subsequent transfusion management can be challenging and often poses a problem in finding the compatible blood for transfusion. The aim of this study was to investigate the specificity of the antibody to the HFA causing a hemolytic transfusion reaction (HTR) and procure the compatible blood unit for future transfusion. CASE PRESENTATION: A 4-year-old female met with a head injury that led to intracranial bleeding and surgical intervention was required to remove blood clots. In the face of anemia, blood transfusion was planned. The pretransfusion tests on her blood sample revealed the presence of a pan-reactive alloantibody with hemolytic properties. She was transfused with 10 mL of the least incompatible red blood cells (RBCs) to which she reacted with signs of clinical hemolysis, i.e., chill, rigor, fever, and hemoglobinuria, on 3 different occasions. Despite her anemia, she was managed by medical intervention only. Her antibody reacted with all RBCs tested, except autologous and P-null (p phenotype) cells. Her RBCs did not react with anti-PP1Pk, which corroborated her phenotype as P-null. The genomic study revealed she was hemi- or homozygous or for a deletion of 26-bp in A4GALTexon 3, previously reported as causing the P-null phenotype and designated A4GALT*01N.019. CONCLUSION: This report documents a rare case of the P-null phenotype with an alloanti-PP1Pk causing a severe HTR to transfusion of the trial dose of the least incompatible blood. The case is the first example of this specific A4GALTmutation found in India.

17.
Oncogene ; 40(41): 6034-6048, 2021 10.
Article in English | MEDLINE | ID: mdl-34453124

ABSTRACT

BRAF-driven colorectal cancer is among the poorest prognosis subtypes of colon cancer. Previous studies suggest that BRAF-mutant serrated cancers frequently exhibit Microsatellite Instability (MSI) and elevated levels of WNT signaling. The loss of tumor-suppressor Smad4 in oncogenic BRAF-V600E mouse models promotes rapid serrated tumor development and progression, and SMAD4 mutations co-occur in human patient tumors with BRAF-V600E mutations. This study assesses the role of SMAD4 in early-stage serrated tumorigenesis. SMAD4 loss promotes microsatellite stable (MSS) serrated tumors in an oncogenic BRAF-V600E context, providing a model for MSS serrated cancers. Inactivation of Msh2 in these mice accelerated tumor formation, and whole-exome sequencing of both MSS and MSI serrated tumors derived from these mouse models revealed that all serrated tumors developed oncogenic WNT mutations, predominantly in the WNT-effector gene Ctnnb1 (ß-catenin). Mouse models mimicking the oncogenic ß-catenin mutation show that the combination of three oncogenic mutations (Ctnnb1, Braf, and Smad4) are critical to drive rapid serrated dysplasia formation. Re-analysis of human tumor data reveals BRAF-V600E mutations co-occur with oncogenic mutations in both WNT and SMAD4/TGFß pathways. These findings identify SMAD4 as a critical factor in early-stage serrated cancers and helps broaden the knowledge of this rare but aggressive subset of colorectal cancer.


Subject(s)
Colorectal Neoplasms/metabolism , Proto-Oncogene Proteins B-raf/metabolism , Smad4 Protein/metabolism , Animals , Carcinogenesis , Colorectal Neoplasms/pathology , Disease Models, Animal , Humans , Mice
18.
Asian J Transfus Sci ; 15(1): 12-15, 2021.
Article in English | MEDLINE | ID: mdl-34349451

ABSTRACT

BACKGROUND: Discrepancy in "forward/reverse" grouping leads to confusion in assigning ABO group to a person. It could be genetic in nature and classified according to the presence/absent of antigen on red blood cell (RBC) vis-a-vis corresponding alloantibody in plasma. AIM: The aim of the study was to investigate the grouping anomaly found in a recently delivered woman who required transfusion. MATERIALS AND METHODS: A standard protocol for investigation was followed. RESULTS: A 27-year-old female, gravida 4, para 3, was grouped O on forward grouping, but her serum did not agglutinate Group B RBCs tested. Absorption-elution study gave an active eluate from her sensitized RBCs with anti-B or anti-A+B. Saliva showed H, but no B antigens indicating to her Bel phenotype. However, 2-week latter in the follow-up study, her serum revealed a presence of complement binding high titer anti-B. The problem of missing anti-B on the previous occasion was attributed to hemagglutination inhibition caused by accumulated complement macromolecules on RBCs that gave rise to physical hindrance in the formation hemagglutination clumps. CONCLUSION: The unusual case of erroneous reversed grouping was attributed to complement-mediated hemagglutination inhibition. The positive eluate obtained from sensitized RBCs of the mother was considered to be due to a contamination of fetal RBCs in maternal circulation entered during her postpartum phase of pregnancy. It could also be due to a conversion of H to B antigen no matter in trace amount by the fetal B group-specific transferase percolated into maternal circulation.

19.
Trop Doct ; 51(3): 398-403, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34013811

ABSTRACT

Our observational cross-sectional study looked at the risk factors, diagnosis, management and outcomes of placenta accrete spectrum at the Christian Medical College and Hospital, Vellore, India, between January 2013 and December 2018. A total of 21 cases of placenta accrete spectrum are described among whom a preop diagnosis was available in 14 cases. A previous history of Caesarean section and placenta previa was present in 90%. Caesarean hysterectomy was carried out in 80%, but none of those managed conservatively required interval hysterectomy. Urinary tract injury was the most common surgical complication, seen in over 50%. The mean blood loss was 3.5 l and 14 patients required intensive care unit admission, but no maternal mortality ensued. Thus, we conclude that the conservative management in carefully selected cases is feasible.


Subject(s)
Cesarean Section/adverse effects , Hysterectomy/methods , Placenta Accreta/surgery , Postpartum Hemorrhage/prevention & control , Adult , Cesarean Section/methods , Cross-Sectional Studies , Female , Humans , Maternal Mortality , Placenta Accreta/diagnosis , Placenta Accreta/epidemiology , Postoperative Complications , Pregnancy , Retrospective Studies , Urinary Tract/injuries , Uterus/surgery
20.
Asian J Transfus Sci ; 14(1): 60-62, 2020.
Article in English | MEDLINE | ID: mdl-33162709

ABSTRACT

BACKGROUND: Antibodies to the Kidd blood group are mainly red blood cell (RBC) immune, but a few reports on naturally occurring antibodies have been documented. AIM: The aim of this study is to study the anti-Jk(a) for its unusual reactivity with different serological methods. MATERIALS AND METHODS: Donor's plasma was tested with RBCs from in house donors and commercial panels by manual and automated devices. RESULTS: A 36-year-old male blood donor with naturally occurring anti-Jk(a) is detected by solid-phase assays and the gel card technique but not by the tube method. The IgG antibody with the titer of >32 was not a complement-fixing hemolysin, showed a reduced reactivity with enzyme-treated RBCs, and was detectable through 8 months' follow-up period. The donor was typed as (Jk(a-). CONCLUSION: An unusual naturally occurring anti-Jk(a) detected by solid-phase red-cell adherence but not reacting by tube technique reflected on the sensitivity of the methods used.

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