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1.
Lung India ; 41(2): 110-114, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38700404

RESUMEN

BACKGROUND: Studies on the relationship between asthma and various parameters of fasting lipid profile have reported conflicting results. In this study, we intend to explore this association between asthma and its level of control with fasting serum lipid profile further. METHODS: In our observational prospective cohort study, we studied 107 known asthmatic patients presenting in large tertiary care centre of North India. Fasting serum samples for lipid profile reports of all patients were collected. Patients were divided into controlled and uncontrolled asthma groups on the basis of clinical symptoms and spirometric findings. We evaluated the statistical difference and significance for various lipid profile parameters in between two groups using an independent t-test. RESULTS: On comparing the fasting lipid profile of 38 patients with uncontrolled asthma and 69 patients with controlled asthma, we found that serum levels of low-density lipoprotein (LDL) and ratio of total cholesterol to high-density lipoprotein (TC: HDL) were significantly higher among patients with uncontrolled asthma. On statistical analysis, their P values were 0.03 and 0.047, respectively. CONCLUSION: Serum levels of LDL and ratio of TC: HDL were higher in patients with uncontrolled asthma.

2.
Birth Defects Res ; 116(5): e2348, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38801241

RESUMEN

BACKGROUND: Absent or hypoplastic nasal bone (AHNB) on first or second-trimester ultrasonography (USG) is an important soft marker of Down syndrome. However, due to its varied incidence in euploid and aneuploid fetuses, there is always a dilemma of whether to go for invasive fetal testing for isolated AHNB. This study aims to assess outcomes specifically within the context of Indian ethnicity women. MATERIALS AND METHODS: This was a prospective observational study. All patients who reported with AHNB in the first- or second-trimester USG were included. Genetic counseling was done, and noninvasive and invasive testing was offered. Chromosomal anomalies were meticulously recorded, and pregnancy was monitored. RESULTS: The incidence of AHNB in our study was 1.16% (47/4051). Out of 47 women with AHNB, the isolated condition was seen in 32 (0.78%) cases, while AHNB with structural anomalies was seen in nine cases (0.22%). Thirty-nine women opted for invasive testing. Six out of 47 had aneuploidy (12.7%), while two euploid cases (4.25%) developed nonimmune hydrops. The prevalence of Down syndrome in fetuses with AHNB was 8.5% (4/47) and 0.42% (17/4004) in fetuses with nasal bone present. This difference was statistically significant (p = .001). CONCLUSION: The results indicate that isolated AHNB cases should be followed by a comprehensive anomaly scan rather than immediately recommending invasive testing. However, invasive testing is required when AHNB is associated with other soft markers or abnormalities. As chromosomal microarray is more sensitive than standard karyotype in detecting chromosomal aberrations, it should be chosen over karyotype.


Asunto(s)
Síndrome de Down , Hueso Nasal , Ultrasonografía Prenatal , Humanos , Femenino , Hueso Nasal/anomalías , Hueso Nasal/diagnóstico por imagen , Embarazo , Estudios Prospectivos , Síndrome de Down/genética , Adulto , Ultrasonografía Prenatal/métodos , Aneuploidia , India , Asesoramiento Genético , Diagnóstico Prenatal/métodos , Padres , Segundo Trimestre del Embarazo , Aberraciones Cromosómicas
3.
J Family Med Prim Care ; 13(3): 990-996, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38736772

RESUMEN

Background: Mobile health applications are an established tool for healthcare management, patient education, and even capacity building for healthcare providers. However, its use among traditional birth attendants (TBAs) is limited. The aim of this study is to explore the needs and bottlenecks of developing an interactive mobile application for maternal and infant care (MAI) of TBAs. Materials and Methods: It is a qualitative study having in-depth interviews (face-to-face approach) conducted among the seekers of MAI services. Setting: This study is conducted in tribal and rural locations in the district Sirohi, Rajasthan. Participants: TBAs and tribal females of reproductive age in tribal-dominated areas have participated. The development of an interactive mobile application MAI has three phases: (1) a need-based approach to identify the needs on the ground; (2) identifying intervention bottlenecks and possible solutions; (3) design and development of the mobile application. Results: Ninety-six tribal females of reproductive age participated in the needs assessment. Eighty percent of them were ≤ 30 years of age and 40% of them were uneducated. Most participants informed that lack of information (culturally/locally appropriate content), peer advocacy, affordability, lack of transportation, and the influence of TBAs are the significant factors for less uptake of maternity and child health services in the tribal and rural areas. Conclusion: The MAI app has culturally/locally appropriate content and is prepared by the local TBAs and Accredited Social Health Activists, with full local character and clothing. MAI app has videos and audio in the local language (Marwari) with pictorial quizzes. Using the MAI app, TBAs may self-educate and guide tribal pregnant women about maternal hygiene and infant healthcare as needed at various stages of pregnancy and childbirth.

4.
Maedica (Bucur) ; 19(1): 37-41, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38736912

RESUMEN

Background: Heart disease is the important cause of maternal morbidity and mortality during the antepartum and postpartum period. The prevalence of heart disease during pregnancy varies from 0.3 to 3.5% (2). We aimed to know the spectrum of heart disease in pregnancy and its impact on the maternal and fetal outcome. Methodology: The study was conducted in the Department of Obstetrics and Gynecology of the tertiary care referral Centre of Western Rajasthan, India. Data from November 2019 to October 2021 were collected from the labour room and obstetric ward records. Results:Forty-eight pregnant women were diagnosed with heart disease over a period of two years. The prevalence of heart disease in pregnancy was 1.3%. Rheumatic heart disease was the main cardiac lesion (85.42%), with mitral stenosis being the most commonly seen (31.25%). Previous cardiac surgery was found in 14.58% of patients. Half of women gave birth by spontaneous vaginal delivery (50%), 43.75% of subjects by cesarean section and 6.25% of participants underwent instrumental delivery. Admissions to intensive care unit (ICU) were noted in 16.67% of cases, and those to neonatal intensive care unit (NICU) in nine newborns (18.75%). There were only two maternal deaths and no baby born with congenital heart disease. Conclusion:Heart disease in pregnancy is a high-risk condition and significantly impacts the mother and fetal outcome. By proper antenatal, intrapartum and postnatal supervision under a multidisciplinary team, maternal and fetal mortality and morbidity can be reduced.

6.
J Pharm Bioallied Sci ; 16(Suppl 1): S156-S158, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38595474

RESUMEN

Introduction: The application of the antioxidants after the teeth are bleached has been advocated to fasten the restorative process post-bleaching. The motive of this study was to examine and assess the micro-tensile binding strength of bleached enamel to the resin using a variety of antioxidant solutions. Finding the reason for the tooth fracture was the secondary outcome measured. Materials and Methods: An in vitro study was planned with 100 human extracted teeth, with 20 in each group with one as controls and 4 others tested for the antioxidants sodium ascorbate, epigallocatechin gallate, chitosan, and proanthocyanidin application. The bond strength of bleached enamel to the resin was well as the failure type was assessed after the values were noted and compared using the ANOVA and Tukey's methods keeping P < 0.05 as significant. Results: Epigallocatechin gallate specimens displayed the maximum micro-tensile bond strength under the investigational circumstances, whereas controls displayed the lowest micro-tensile bond strength. There was statistical alteration in micro-tensile bond strengths between all the groups except between epigallocatechin gallate vs chitosan and sodium ascorbate vs proanthocyanidin. High statistical significance was seen between the control and the antioxidant groups as well as between sodium ascorbate and epigallocatechin gallate and chitosan. Conclusion: The antioxidant chemicals significantly augmented the bond strength of bleached enamel to the resin that had been bleached. Also, when compared to the other experimental groups, epigallocatechin gallate and chitosan treatment displayed the greatest mean bond strength values.

7.
J Pharm Bioallied Sci ; 16(Suppl 1): S209-S211, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38595581

RESUMEN

Background: The most common and convenient technique to provide antiplaque medicines is through mouth rinses, which have the advantage of accessing places that are difficult for a toothbrush to clean. Chlorhexidine and Listerine mouthwashes were tested for their effectiveness when used in addition to routine teeth cleaning techniques. However, the studies assessing the antibacterial effects of these among young adults are diversified and limited. Materials and Methods: This comparative study was conducted among 240 schoolchildren. The participants were separated into three groups: A, B, and C. The research was conducted at two intervals of time, before therapy and during treatment period. The plaque was assessed through the plaque index (Turesky modification of Quigley-Hein plaque index (1970)). After a month, individuals had oral examination and were assessed. Results: Following the first week, a comparison of plaque scores was made between the three groups. Plaque score is lower in group C and group B than in group A in the succeeding second, third, and fourth weeks, but Tukey's test results suggest that group C has a larger decrease in plaque than group B. Conclusion: According to this study, as compared to a placebo mouthwash, both a mouthwash containing 0.2% chlorhexidine and one containing phenol dramatically reduced plaque development and gingival irritation.

8.
BMJ Open Qual ; 13(Suppl 1)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589043

RESUMEN

BACKGROUND: Early skin-to-skin contact (SSC) at birth has been shown to improve neonatal outcomes due to enhanced cardiorespiratory stability, thermoregulation and breastfeeding success. LOCAL PROBLEM: The practice of early SSC was virtually non-existent in our delivery room (DR). METHODS AND INTERVENTIONS: The study was conducted in a newly established tertiary care teaching hospital in Western Rajasthan, India. We aimed to improve the median duration of early SSC from 0 min to at least 60 min over 24 weeks in our DR. A quality improvement (QI) team was formed, and all inborn infants ≥35 weeks born vaginally from 9 March 2017 were included. Using the tools of point-of-care QI, we found the lack of standard operating procedure, lack of knowledge among nursing staff regarding early SSC, routine shifting of all infants to radiant warmer, the practice of prioritising birthweight documentation and vitamin K administration as the major hindrances to early SSC. Various change ideas were implemented and tested sequentially through multiple plan-do-study-act (PDSA) cycles to improve the duration of early SSC. Interventions included framing a written policy for SSC, sensitising the nursing staff and resident doctors, actively delaying the alternate priorities, making early SSC a shared responsibility among paediatricians, obstetricians, nursing staff and family members, and continuing SSC in the recovery area of the DR complex. RESULTS: The duration of early SSC increased from 0 to 67 min without any additional resources. The practice of SSC got well established in the system as reflected by a sustained improvement of 63 min and 72 min, respectively, at the end of 2 months and 4 years after study completion. CONCLUSION: Using the QI approach, we established and sustained the practice of early SSC for more than 60 min in our unit by using system analysis and testing change ideas in sequential PDSA cycles.


Asunto(s)
Método Madre-Canguro , Mejoramiento de la Calidad , Recién Nacido , Lactante , Niño , Humanos , Embarazo , Femenino , Método Madre-Canguro/métodos , India , Vitamina K , Factores de Tiempo
9.
Genet Test Mol Biomarkers ; 28(5): 207-212, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38533877

RESUMEN

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular life-threatening disorder. Owing to high carrier frequency, population-wide SMA screening to quantify the copy number of SMN gene is recommended by American College of Medical Genetics and Genomics. An accurate, reliable, short runaround time and cost-effective method may be helpful in mass population screening for SMA. Methods: Multiplex ligation-dependent probe amplification (MLPA) is a gold standard to estimate the copy number variation (CNV) for SMN1 and SMN2 genes. In this study, we validated droplet digital polymerase chain reaction (ddPCR) for the determination of CNV for both SMN1 and SMN2 exon 7 for a diagnostic purpose. In total, 66 clinical samples were tested using ddPCR, and results were compared with the MLPA as a reference test. Results: For all samples, CNV for SMN1 and SMN2 exon 7 was consentaneous between ddPCR and MLPA test results (κ = 1.000, p < 0.0001). In addition, ddPCR also showed a significant acceptable degree of test repeatability, coefficient of variation < 4%. Conclusion: ddPCR is expected to be utilitarian for CNV detection for carrier screening and diagnosis of SMA. ddPCR test results for CNV detection for SMN1/SMN2 exon 7 are concordant with the gold standard. ddPCR is a more cost-effective and time-saving diagnostic test for SMA than MLPA. Furthermore, it can be used for population-wide carrier screening for SMA.


Asunto(s)
Variaciones en el Número de Copia de ADN , Exones , Tamización de Portadores Genéticos , Reacción en Cadena de la Polimerasa Multiplex , Atrofia Muscular Espinal , Proteína 1 para la Supervivencia de la Neurona Motora , Proteína 2 para la Supervivencia de la Neurona Motora , Humanos , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/diagnóstico , Proteína 1 para la Supervivencia de la Neurona Motora/genética , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Variaciones en el Número de Copia de ADN/genética , Tamización de Portadores Genéticos/métodos , Reacción en Cadena de la Polimerasa Multiplex/métodos , Exones/genética , Femenino , Masculino , Pruebas Genéticas/métodos , Heterocigoto , Reproducibilidad de los Resultados
10.
Int J Biol Macromol ; 264(Pt 2): 130771, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38467220

RESUMEN

Development of the efficient hemostatic materials is an essential requirement for the management of hemorrhage caused by the emergency situations to avert most of the casualties. Such injuries require the use of external hemostats to facilitate the immediate blood clotting. A variety of commercially available hemostats are present in the market but most of them are associated with limitations such as exothermic reactions, low biocompatibility, and painful removal. Thus, fabrication of an ideal hemostatic composition for rapid blood clot formation, biocompatibility, and antimicrobial nature presents a real challenge to the bioengineers. Benefiting from their tunable fabrication properties, alginate-based hemostats are gaining importance due to their excellent biocompatibility, with >85 % cell viability, high absorption capacity exceeding 500 %, and cost-effectiveness. Furthermore, studies have estimated that wounds treated with sodium alginate exhibited a blood loss of 0.40 ± 0.05 mL, compared to the control group with 1.15 ± 0.13 mL, indicating its inherent hemostatic activity. This serves as a solid foundation for designing future hemostatic materials. Nevertheless, various combinations have been explored to further enhance the hemostatic potential of sodium alginate. In this review, we have discussed the possible role of alginate based composite hemostats incorporated with different hemostatic agents, such as inorganic materials, polymers, biological agents, herbal agents, and synthetic drugs. This article outlines the challenges which need to be addressed before the clinical trials and give an overview of the future research directions.


Asunto(s)
Hemostáticos , Trombosis , Humanos , Hemostáticos/farmacología , Hemostáticos/uso terapéutico , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Alginatos/farmacología , Hemostasis , Coagulación Sanguínea , Hemorragia/tratamiento farmacológico
11.
BMC Womens Health ; 24(1): 144, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38408979

RESUMEN

BACKGROUND: Menstruation is a major physiological change in a woman's life, but lack of knowledge, poor practices, socio-cultural barriers, poor access to products and their improper disposal have significant consequences on health, dignity and well-being of women and adolescent girls. OBJECTIVES: This study aimed to assess the knowledge and practices related to menstrual health and hygiene amongst females of 10-49 years of age; explore the experiences and challenges of women during menstruation; and identify the key predictors of healthy menstrual health and hygiene. METHODS: Using a cross-sectional study design, we adopted a mixed methods approach for data collection. For quantitative household survey, a total of 921 respondents were selected from three districts of Odisha. Qualitative findings through focus group discussions and in-depth interviews supplemented the survey findings and helped to identify the barriers affecting good menstrual practices. Epi data version 2.5 and R 4.2.2 was used for data entry and data analysis, respectively. Descriptive statistics was used to calculate proportion, mean and standard deviation; Chi square test was used to measure the association between categorical variables. Bivariate and multivariate logistics analyses were done to identify predictors of healthy menstrual health and hygiene. For qualitative data analysis, thematic analysis approach was adopted using software Atlas.ti 8. RESULTS: For 74.3% respondents, mothers were the primary source of information; about 61% respondents were using sanitary pad. The mean age at menarche was 12.9 years and almost 46% of respondents did not receive any information about menstruation before menarche. Lower age and education up to higher secondary level or above had statistically significant associations with the knowledge about menstruation. Age, caste, respondent's education, mother's education, sanitation facility, availability of water, accessibility and affordability for sanitary pads were found to be strongly associated with good menstrual hygiene practices. CONCLUSION: Traditional beliefs regarding menstruation still persists at the community level. Educating mothers, increasing awareness about safe menstrual hygiene, providing adequate water and sanitation facilities and ensuring proper disposal of menstruation products need priority attention.


Asunto(s)
Higiene , Menstruación , Femenino , Humanos , Adolescente , Menstruación/fisiología , Higiene/educación , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Productos para la Higiene Menstrual , India , Agua
12.
J Cyst Fibros ; 23(1): 169-171, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37633792

RESUMEN

Pancreatic secretions become viscous and acidic in Cystic fibrosis (CF), highlighting the role of CFTR in pancreatic fluid and bicarbonate secretion. Forskolin-induced swelling (FIS) assay developed in intestinal organoids measures residual CFTR function. It is not known whether FIS reflects bicarbonate secretion in pancreas, an organ that secretes near-isotonic NaHCO3 levels. To investigate this, we generated pancreatic duct organoids from CF and non-CF pigs. Epithelial and ductal origin was confirmed with epithelial markers, ion transporters and lack of acinar, islet cell markers. CF organoids were small with no identifiable lumen; CFTR was expressed only in non-CF organoids. Utilizing FIS, organoid size increased only in response to chloride, not bicarbonate. This report highlights pancreatic duct organoids isolated for the first time from CF pigs and evidence for chloride and not bicarbonate driving pancreatic organoid swelling. These organoids would be useful to test chloride permeability of CFTR mutations that cause CF pancreatic disease.


Asunto(s)
Fibrosis Quística , Animales , Porcinos , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Cloruros/metabolismo , Bicarbonatos/metabolismo , Conductos Pancreáticos/metabolismo , Colforsina/farmacología , Organoides/metabolismo
13.
Autophagy ; 20(1): 131-150, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37649246

RESUMEN

ABBREVIATIONS: atl atlastin; ALR autophagic lysosome reformation; ER endoplasmic reticulum; GFP green fluorescent protein; HSP hereditary spastic paraplegia; Lamp1 lysosomal associated membrane protein 1 PolyUB polyubiquitin; RFP red fluorescent protein; spin spinster; mTor mechanistic Target of rapamycin; VCP valosin containing protein.


Asunto(s)
Autofagia , Drosophila , Animales , Autofagia/fisiología , Lisosomas/metabolismo , Músculos , Serina-Treonina Quinasas TOR/metabolismo
14.
Arch Gynecol Obstet ; 309(2): 413-425, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37179498

RESUMEN

OBJECTIVE: The objective of our study is to estimate the prevalence of endometrial cavity fluid (ECF) in Assisted Reproductive Techniques (ART) cycles and analyze its effects on pregnancy outcome in such cycles. DATA SOURCES: PubMed, Cochrane Central, Scopus, and clinicaltrials.gov were searched for articles. The reference lists of relevant publications were explored for other studies. STUDY ELIGIBILITY CRITERIA: Studies that had assessed the pregnancy outcome in ART cycles and had commented on ECF accumulation were included. Pregnancy outcomes were assessed in all ART cycles where ECF was observed and were compared to the non-ECF cycles. RESULTS: A total of nine studies were included in the meta-analysis for a total of 28,210 cycles. Pooled analysis of the prevalence of ECF cycles out of total cycles in females undergoing ART using a fixed effect model showed that it was 14% (95% CI is 13% to 14%; I2 = 99%, p = < 0.01). The random effect model prevalence of ECF cycles was around 7% (95% CI: 4% to 10%). There was a statistically significant (25%) decrease in pregnancy rates per cycle transfer in the ECF cycle versus the non-ECF cycle group during ART [OR = 0.75, 95% CI = 0.67-0.84), p < 0.001; moderate quality evidence]. When ECF size was compared, there was a statistically significant increase in pregnancy rates if ECF size was less than 3.5 mm versus greater than or equal to 3.5 mm [OR = 13.67, 95% CI = 1.43-130.40), p = 0.02; high quality evidence]. Sub-group analysis revealed that the ECF present at the time of embryo transfer significantly decreased the pregnancy rates by 26% as compared to the group where the ECF was not present at the time of embryo transfer [OR = 0.74, 95% CI = 0.65-0.85), p < 0.001]. CONCLUSIONS: This meta-analysis proposes that the presence of ECF significantly decreases the implantation and pregnancy rates of ART cycles, and even more so if its size is greater than 3.5 mm. Interventions to decrease ECF formation or treat it have enhanced the pregnancy outcome in ART cycles. PROSPERO REGISTRATION: Date: 17th September 2020; Number: CRD42020182262.


Asunto(s)
Endometrio , Nacimiento Vivo , Humanos , Femenino , Embarazo , Nacimiento Vivo/epidemiología , Técnicas Reproductivas Asistidas , Resultado del Embarazo , Índice de Embarazo , Fertilización In Vitro
15.
J Clin Endocrinol Metab ; 109(3): e1072-e1082, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-37931151

RESUMEN

BACKGROUND: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. METHODS: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. RESULTS: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected. CONCLUSION: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.


Asunto(s)
Diabetes Mellitus Tipo 1 , Síndrome de Wolfram , Adolescente , Niño , Preescolar , Humanos , Lactante , Anticuerpos , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/diagnóstico , Mutación , Estudios Prospectivos , Síndrome de Wolfram/diagnóstico
16.
Radiat Res ; 201(1): 7-18, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38019093

RESUMEN

Exposure to high-dose ionizing radiation can lead to life-threatening injuries and mortality. Bone marrow is the most sensitive organ to radiation damage, resulting in the hematopoietic acute radiation syndrome (H-ARS) with the potential sequelae of infection, hemorrhage, anemia, and death if untreated. The development of medical countermeasures (MCMs) to protect or mitigate radiation injury is a medical necessity. In our well-established murine model of H-ARS we have demonstrated that the prostaglandin E2 (PGE2) analog 16,16 dimethyl-PGE2 (dmPGE2) has survival efficacy as both a radioprotectant and radiomitigator. The purpose of this study was to investigate the pharmacokinetics (PK) and biodistribution of dmPGE2 when used as a radioprotector in irradiated and non-irradiated inbred C57BL/6J mice, PK in irradiated and non-irradiated Jackson Diversity Outbred (JDO) mice, and the PK profile of dmPGE2 in non-irradiated non-human primates (NHPs). The C57BL/6J and JDO mice each received a single subcutaneous (SC) dose of 35 ug of dmPGE2 and were randomized to either receive radiation 30 min later or remain non-irradiated. Plasma and tissue PK profiles were established. The NHP were dosed with 0.1 mg/kg by SC administration and the PK profile in plasma was established. The concentration time profiles were analyzed by standard non-compartmental analysis and the metrics of AUC0-Inf, AUC60-480 (AUC from 60-480 min), Cmax, and t1/2 were evaluated. AUC60-480 represents the postirradiation time frame and was used to assess radiation effect. Overall, AUC0-Inf, Cmax, and t1/2 were numerically similar between strains (C57BL/6J and JDO) when combined, regardless of exposure status (AUC0-Inf: 112.50 ng·h/ml and 114.48 ng·h/ml, Cmax: 44.53 ng/ml and 63.96 ng/ml; t1/2: 1.8 h and 1.1 h, respectively). PK metrics were numerically lower in irradiated C57BL/6J mice than in non-irradiated mice [irradiation ratio: irradiated values/non-irradiated values = 0.71 for AUC60-480 (i.e., 29% lower), and 0.6 for t1/2]. In JDO mice, the radiation ratio was 0.53 for AUC60-480 (i.e., 47% lower), and 1.7 h for t1/2. The AUC0-Inf, Cmax, and t1/2 of the NHPs were 29.20 ng·h/ml, 7.68 ng/ml, and 3.26 h, respectively. Despite the numerical differences seen between irradiated and non-irradiated groups in PK parameters, the effect of radiation on PK can be considered minimal based on current data. The biodistribution in C57BL/6J mice showed that dmPGE2 per gram of tissue was highest in the lungs, regardless of exposure status. The radiation ratio for the different tissue AUC60-480 in C57BL/6J mice ranged between 0.5-1.1 (50% lower to 10% higher). Spleen, liver and bone marrow showed close to twice lower exposures after irradiation, whereas heart had a 10% higher exposure. Based on the clearance values from mice and NHP, the estimated allometric scaling coefficient was 0.81 (95% CI: 0.75, 0.86). While slightly higher than the current literature estimates of 0.75, this scaling coefficient can be considered a reasonable estimate and can be used to scale dmPGE2 dosing from animals to humans for future trials.


Asunto(s)
Síndrome de Radiación Aguda , Dinoprostona , Animales , Ratones , Síndrome de Radiación Aguda/tratamiento farmacológico , Ratones Endogámicos C57BL , Primates , Distribución Tisular
17.
Indian J Cancer ; 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-38090972

RESUMEN

BACKGROUND: In advanced-stage epithelial ovarian cancer (EOC) standard of care is upfront debulking surgery (UDS) followed by adjuvant chemotherapy. Interval debulking surgery after neoadjuvant chemotherapy(NACT-IDS) is a reasonable alternative. METHODS: This study was a retrospective review of patients of Stage III/IV EOC treated either by UDS or NACT-IDS between January 2016 and December 2018 to report the comparison of progression-free survival(PFS) and overall survival(OS) of patients with advanced-stage EOC treated with either UDS or NACT-IDS. RESULTS: Out of 50 patients, 19 (38%) underwent UDS, and 31 (62%) received NACT. The mean follow-up duration was 27.7 months. No gross residual disease was achieved in 52.6% of the UDS group and in 70.4% of the NACT-IDS group. The median PFS of 20 and 30 months was observed in the UDS and NACT-IDS groups, respectively (log-rank P = 0.054). The median OS was 36 months in the NACT-IDS group and could not be reached in the UDS group (log-rank P = 0.329). Only residual disease was significantly associated with survival (hazards ratio 3.03, 95% confidence interval: 1.19-7.74) on multivariate Cox regression analysis. CONCLUSIONS: In advanced-stage EOC, the survival outcomes of NACT-IDS are comparable with those of UDS. Apart from the patient-specific parameters, the decision for UDS or NACT-IDS should take in account the expertise of the surgeon and the institutional capacity as a whole.

18.
Braz. J. Anesth. (Impr.) ; 73(6): 782-793, Nov.Dec. 2023. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1520392

RESUMEN

Abstract Objective: To evaluate the efficacy and safety of trans-nasal Sphenopalatine Ganglion (SPG) block over other treatments for Post-Dural Puncture Headache (PDPH) management. Methods: A systematic literature search was conducted on databases for Randomized Controlled Trials (RCTs) comparing trans-nasal SPG blockade for the management of PDPH over other treatment modalities. All outcomes were pooled using the Mantel-Haenszel method and random effect model. Analyses of all outcomes were performed as a subgroup based on the type of control interventions (conservative, intranasal lignocaine puffs, sham, and Greater Occipital Nerve [GON] block). The quality of evidence was assessed using the GRADE approach. Results: After screening 1748 relevant articles, 9 RCTs comparing SPG block with other interventions (6 conservative treatments, 1 sham, 1 GON and 1 intranasal lidocaine puff) were included in this meta-analysis. SPG block demonstrated superiority over conservative treatment in pain reduction at 30 min, 1 h, 2 h, 4 h after interventions and treatment failures with "very low" to "moderate" quality of evidence. The SPG block failed to demonstrate superiority over conservative treatment in pain reduction beyond 6 h, need for rescue treatment, and adverse events. SPG block demonstrated superiority over intranasal lignocaine puff in pain reduction at 30 min, 1 h, 6 h, and 24 h after interventions. SPG block did not show superiority or equivalence in all efficacy and safety outcomes as compared to sham and GON block. Conclusion: Very Low to moderate quality evidence suggests the superiority of SPG block over conservative treatment and lignocaine puff for short-term pain relief from PDPH. PROSPERO Registration: CRD42021291707.


Asunto(s)
Humanos , Cefalea Pospunción de la Duramadre/terapia , Bloqueo del Ganglio Esfenopalatino/métodos , Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Lidocaína
19.
Am J Obstet Gynecol ; 2023 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-38151222

RESUMEN

OBJECTIVE: To assess the effect of intravenous tranexamic acid (1 g) in reducing blood loss during the 3rd and 4th stages of labor following vaginal delivery, in addition to active management of the third stage of labor. METHODS: This double-blinded randomized controlled trial included 650 women with singleton pregnancies of ≥ 34 weeks gestation undergoing vaginal delivery. Eligible women were randomly assigned to receive 1 g of tranexamic acid or placebo intravenously in addition to active management of the third stage of labor. Calibrated blood collection bags were used to measure postpartum blood loss during the 3rd and 4th stages of labor. RESULTS: Out of 886 expectant women who were approached, 650 instances that met the study's inclusion criteria were enrolled and a total of 320 women in group A and 321 in group B were analyzed. Maternal characteristics did not differ between the two groups. Mean blood loss did not differ significantly among the intervention and placebo groups (378.5±261.2 ml vs. 383±258.9 ml; p = 0.93). The incidence of primary postpartum hemorrhage was comparable in both groups (Group A: 15.9%, Group B: 15.3%, p = 0.814). The median fall in haemoglobin within 12-24 hours following delivery in both groups was comparable (group A: 0.60 g% with interquartile range (IQR) 0.4-0.9 g %; group B: 0.6 g% with IQR 0.4-0.8 g %; p = 0.95). The most common adverse effect reported was dizziness. No thromboembolic events were reported at the follow-up of three months in both groups. CONCLUSION: Prophylactic use of tranexamic acid in addition to active management of the third stage of labor does not help further reduce postpartum blood loss following vaginal delivery.

20.
J Midlife Health ; 14(2): 81-86, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38029026

RESUMEN

Background and Aims: Programmed death ligand-1 (PD-L1) is a co-regulatory molecule that suppresses local immunity, and mismatch repair (MMR) deficiency (dMMR) is reported to influence the response to anti-PD-L1-targeted therapy. This study was conducted to find the PD-L1 status, the occurrence of dMMR in endometrial carcinomas, and the association between them. Materials and Methods: The study included 35 resected specimens of endometrial carcinomas represented on formalin-fixed paraffin-embedded sections from January 2016 to July 2020. The clinicopathologic information including patient age, tumor histologic type, grade, stage, lymphovascular invasion, the extent of myometrial invasion, and the percentage of tumor-infiltrating lymphocytes (TILs) were obtained in all cases. The expression of PD-L1 and MMR antibodies including mutS homolog 2 (MSH-2), MSH-6, mutL homolog 1 (MLH-1) and MLH-3, and postmeiotic segregation 2 were assessed using immunohistochemistry. The statistical analysis was done using the Statistical Package for the Social Sciences (SPSS) version 26. Results: PD-L1 expression was noted in 48.6% of the cases in tumor cells and 65.7% of the cases in TILs and MMR was deficient in 28.6% of endometrial carcinomas. A statistically significant relation was noted between dMMR and TILs, PD-L1 expression in tumor cells and TILs, PD-L1 expression in tumor cells, and extent of myometrial invasion. Although there was no statistically significant association between MMR status and PD-L1 expression in tumor cells or TILs, 60% of patients with dMMR were PD-L1 positive. Conclusion: Sixty percent of dMMR cases showed PD-L1 expression in tumor cells. We conclude, ECs that are MMR deficient might get better response to anti-PD-L1 therapy. This study also revealed the prognostic use of TILs in PD-L1-expressed tumors.

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