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Aim: To investigate the possible role of systemic inflammatory markers (interleukin; IL-6, C-reactive protein; CRP, and albumin levels) in the development of Alzheimer's dementia (AD) and also find their association with the severity of disease. Material and Methods: It was a cross-sectional study. Patients with Alzheimer's dementia (AD) and vascular dementia (VaD) from outpatient settings in tertiary care hospitals and non-demented controls (NDC) were recruited from the community. Individuals aged 50 years and older (n = 110) were included. Serum levels of IL-6, CRP, and albumin levels in patients with AD, VaD, and NDC were measured. The clinical Dementia Rating Scale was used for staging the severity of dementia. Serum levels of IL-6, CRP, and serum albumin were compared in study subjects and also analyzed with the severity of dementia in dementia subgroups. Results: Our main finding was that serum levels of IL-6 were significantly elevated in patients with AD and VaD (7.79 and 6.60) as compared to NDC (2.98) (P < 0.001). No significant difference in CRP or albumin levels was observed between the three groups. Serum IL-6 and CRP showed a positive correlation with the severity of AD, though the correlation was significant only for IL-6 (r = 0.777). The serum albumin levels showed a statistically significant negative correlation with the severity of AD (r > 0.3 but <0.5). Conclusion: The study demonstrates a notable association between systemic inflammatory markers, particularly IL-6, and the severity of AD, indicating their potential role in its pathogenesis. These findings suggest that targeting these markers could offer new insights into therapeutic strategies for AD.
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PURPOSE: This study aimed to develop a classifier using supervised machine learning to effectively assess the impact of clinical, demographical, and biochemical factors in accurately predicting the antiseizure medications (ASMs) treatment response in people with epilepsy (PWE). METHODS: Data was collected from 786 PWE at the Outpatient Department of Neurology, Institute of Human Behavior and Allied Sciences (IHBAS), New Delhi, India from 2005 to 2015. Patients were followed up at the 2nd, 4th, 8th, and 12th month over the span of 1 year for the drugs being administered and their dosage, the serum drug levels, the frequency of seizure control, drug efficacy, the adverse drug reactions (ADRs), and their compliance to ASMs. Several features, including demographic details, medical history, and auxiliary examinations electroencephalogram (EEG) or Computed Tomography (CT) were chosen to discern between patients with distinct remission outcomes. Remission outcomes were categorized into 'good responder (GR)' and 'poor responder (PR)' based on the number of seizures experienced by the patients over the study duration. Our dataset was utilized to train seven classical machine learning algorithms i.e Extreme Gradient Boost (XGB), K-Nearest Neighbor (KNN), Support Vector Classifier (SVC), Decision Tree (DT), Random Forest (RF), Naïve Bayes (NB) and Logistic Regression (LR) to construct classification models. RESULTS: Our research findings indicate that 1) among the seven algorithms examined, XGB and SVC demonstrated superior predictive performances of ASM treatment outcomes with an accuracy of 0.66 each and ROC-AUC scores of 0.67 (XGB) and 0.66 (SVC) in distinguishing between PR and GR patients. 2) The most influential factor in discerning PR to GR patients is a family history of seizures (no), education (literate) and multitherapy with Chi-square (χ2) values of 12.1539, 8.7232 and 13.620 respectively and odds ratio (OR) of 2.2671, 0.4467, and 1.9453 each. 3). Furthermore, our surrogate analysis revealed that the null hypothesis for both XGB and SVC was rejected at a 100â¯% confidence level, underscoring the significance of their predictive performance. These findings underscore the robustness and reliability of XGB and SVC in our predictive modelling framework. SIGNIFICANCE: Utilizing XG Boost and SVC-based machine learning classifier, we successfully forecasted the likelihood of a patient's response to ASM treatment, categorizing them as either PR or GR, post-completion of standard epilepsy examinations. The classifier's predictions were found to be statistically significant, suggesting their potential utility in improving treatment strategies, particularly in the personalized selection of ASM regimens for individual epilepsy patients.
Subject(s)
Anticonvulsants , Epilepsy , Machine Learning , Humans , India , Anticonvulsants/therapeutic use , Male , Female , Adult , Epilepsy/drug therapy , Middle Aged , Treatment Outcome , Young Adult , Adolescent , Algorithms , Seizures/drug therapy , Electroencephalography/methods , Child , Support Vector MachineABSTRACT
Excess of selenium (Se) in aquatic ecosystems has necessitated thorough investigations into the effects/consequences of this metalloid on the autochthonous organisms exposed to it. The molecular details of Se-mediated adaptive response remain unknown in cyanobacteria. This study aims to uncover the molecular mechanisms driving the divergent physiological responses of cyanobacteria on exposure to selenate [Se(VI)] or selenite [Se(IV)], the two major water-soluble oxyanions of Se. The cyanobacterium, Anabaena PCC 7120, withstood 0.4 mM of Se(VI), whereas even 0.1 mM of Se(IV) was detrimental, affecting photosynthesis and enhancing endogenous ROS. Surprisingly, Anabaena pre-treated with Se(VI), but not Se(IV), showed increased tolerance to oxidative stress mediated by H2O2/methyl viologen. RNA-Seq analysis showed Se(VI) to elevate transcription of genes encoding anti-oxidant proteins and Fe-S cluster biogenesis, whereas the photosynthesis-associated genes, which were mainly downregulated by Se(IV), remained unaffected. Specifically, the content of typical 2-Cys-Prx (Alr4641), a redox-maintaining protein in Anabaena, was elevated with Se(VI). In comparison to the wild-type, the Anabaena strain over-expressing the Alr4641 protein (An4641+) showed enhanced tolerance to Se(VI) stress, whereas the corresponding knockdown-strain (KD4641) was sensitive to this stressor. Incidentally, among these strains, only An4641+ was better protected from the ROS-mediated damage caused by high dose of Se(VI). These results suggest that altering the content of the antioxidant protein 2-Cys-Prx, could be a potential strategy for modulating resistance to selenate. Thus, involvement of oxidative stress machinery appears to be the major determinant, responsible for the contrasting physiological differences observed in response to selenate/selenite in cyanobacteria.
Subject(s)
Anabaena , Oxidative Stress , Oxidative Stress/drug effects , Anabaena/metabolism , Anabaena/genetics , Anabaena/drug effects , Photosynthesis/drug effects , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Selenium/metabolism , Selenium/pharmacology , Adaptation, Physiological/drug effects , Selenious Acid/pharmacology , Selenious Acid/metabolism , Reactive Oxygen Species/metabolism , Selenic Acid/pharmacology , Selenic Acid/metabolism , Gene Expression Regulation, Bacterial/drug effectsABSTRACT
INTRODUCTION: Gestational diabetes mellitus (GDM) is defined as glucose intolerance in a female with its onset or first recognition during pregnancy. Females with GDM are at higher risk of developing antenatal complications like preeclampsia during pregnancy and increased risk of type 2 diabetes as well as cardiovascular disorders later in their life. Maternal thyroid changes in the first and second trimesters of pregnancy have been widely related to the risk of GDM. Hypothyroidism during pregnancy is associated with early and late complications like abortions, anaemia, gestational hypertension, placental abruption and postpartum haemorrhage, impaired infant neurodevelopment, and low birth weight. OBJECTIVES: This study aims to compare the thyroid function test (TFT) (serum fT3, fT4, TSH) and thyroid peroxidase antibody (anti TPO) between GDM and non GDM pregnant women in the second trimester and to correlate the adverse pregnancy outcomes with TFT in GDM and non GDM women. METHODS: A nested case-control study was done in the Department of Obstetrics and Gynaecology, Department of Endocrinology, Department of Paediatrics, University College of Medical Sciences, and Guru Teg Bahadur (GTB) Hospital, Delhi. About 350 pregnant women from 13 weeks till 28 weeks period of gestation were screened out of which 40 GDM and 40 non GDM women were selected after performing an oral glucose tolerance test (OGTT). A TFT and anti TPO test were compared between GDM and non GDM participants. Furthermore, various parameters like sociodemographic profile, mode of delivery, pregnancy outcomes, and adverse maternal and adverse neonatal outcomes were compared. CONCLUSION: The mean age of GDM women is found to be more than non GDM women. The mean TFT values are significantly lower in women with GDM as compared to non GDM women. In addition, higher values of anti TPO antibody (thyroid autoantibody) were found in the GDM group which aids in insulin resistance. Maternal complications like polyhydramnios, preterm labour, and pregnancy-induced hypertension were found to be more frequent in the GDM group compared to the non GDM group, but the results were statistically not significant. There was a higher incidence of caesarean delivery in the GDM group. Thus, we recommend the implementation of routine thyroid function profile testing in all antenatal females especially those who are at risk of developing GDM. Our study is one of the few Indian studies to evaluate the association of TFT in GDM, and we recommend similar research with a larger sample size and postnatal follow-up.
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Rapidly rising population and climate changes are two critical issues that require immediate action to achieve sustainable development goals. The rising population is posing increased demand for food, thereby pushing for an acceleration in agricultural production. Furthermore, increased anthropogenic activities have resulted in environmental pollution such as water pollution and soil degradation as well as alterations in the composition and concentration of environmental gases. These changes are affecting not only biodiversity loss but also affecting the physio-biochemical processes of crop plants, resulting in a stress-induced decline in crop yield. To overcome such problems and ensure the supply of food material, consistent efforts are being made to develop strategies and techniques to increase crop yield and to enhance tolerance toward climate-induced stress. Plant breeding evolved after domestication and initially remained dependent on phenotype-based selection for crop improvement. But it has grown through cytological and biochemical methods, and the newer contemporary methods are based on DNA-marker-based strategies that help in the selection of agronomically useful traits. These are now supported by high-end molecular biology tools like PCR, high-throughput genotyping and phenotyping, data from crop morpho-physiology, statistical tools, bioinformatics, and machine learning. After establishing its worth in animal breeding, genomic selection (GS), an improved variant of marker-assisted selection (MAS), has made its way into crop-breeding programs as a powerful selection tool. To develop novel breeding programs as well as innovative marker-based models for genetic evaluation, GS makes use of molecular genetic markers. GS can amend complex traits like yield as well as shorten the breeding period, making it advantageous over pedigree breeding and marker-assisted selection (MAS). It reduces the time and resources that are required for plant breeding while allowing for an increased genetic gain of complex attributes. It has been taken to new heights by integrating innovative and advanced technologies such as speed breeding, machine learning, and environmental/weather data to further harness the GS potential, an approach known as integrated genomic selection (IGS). This review highlights the IGS strategies, procedures, integrated approaches, and associated emerging issues, with a special emphasis on cereal crops. In this domain, efforts have been taken to highlight the potential of this cutting-edge innovation to develop climate-smart crops that can endure abiotic stresses with the motive of keeping production and quality at par with the global food demand.
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Edible Grain , Plant Breeding , Animals , Edible Grain/genetics , Plant Breeding/methods , Crops, Agricultural/genetics , Genetic Markers , Genomics/methodsABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of sublingual methylcobalamin for the treatment of vitamin B12 deficiency anemia in children. METHODS: A single arm intervention study was conducted between November, 2020 and April, 2022 in children aged 1-12 years with vitamin B12 deficiency anemia. Children aged 1-6 years received a tablet of methylcobalamin (1500 mcg) by sublingual route every alternate day (three doses) while those aged 7-12 years received five such doses. Thereafter, one such sublingual tablet was given weekly and all participants were followed-up for 6 weeks. RESULTS: 37 children with a mean (SD) age of 8.2 (4.1) years were treated and followed up prospectively. On day 10, no child needed rescue therapy with parenteral methylcobalamin. After 6 weeks, the mean (SD) serum cobalamin (mL) increased from 123.3 (35.5) pg/mL to 507.3 (274.2) pg/mL (P<0.001), plasma homocysteine (L) decreased from 48.9 (17.8) pg/mL to 16.3 (8.5) µmol/L (P<0.001), the mean (SD) hemoglobin increased by 2.3 (1.1) g/dL (P<0.001), and MCV decreased by 12.9 (6.8) fL (P<0.001). 67.6% children persisted to have anemia, albeit majority of them had mild or moderate anemia. There were no unsolicited side-effect reported. CONCLUSION: Sublingual methylcobalamin is effective for the treatment of vitamin B12 deficiency anemia in children; although, the duration of treatment needs to be longer than six weeks.
Subject(s)
Anemia , Gastrointestinal Diseases , Vitamin B 12 Deficiency , Humans , Child , Vitamin B 12 Deficiency/drug therapy , Vitamin B 12/therapeutic use , Tablets/therapeutic useABSTRACT
Thioredoxins (Trxs) are ubiquitous proteins that play vital roles in several physiological processes. Alr2205, a thioredoxin-like protein from Anabaena PCC 7120, was found to be evolutionarily closer to the Trx-domain of the NADPH-Thioredoxin Reductase C than the other thioredoxins. The Alr2205 protein showed disulfide reductase activity despite the presence a non-canonical active site motif 'CPSC'. Alr2205 not only physically interacted with, but also acted as a physiological reductant of Alr4641 (the typical 2-Cys-Peroxiredoxin from Anabaena), supporting its peroxidase function. Structurally, Alr2205 was a monomeric protein that formed an intramolecular disulfide bond between the two active site cysteines (Cys-38 and Cys-41). However, the Alr2205C41S protein, wherein the resolving cysteine was mutated to serine, was capable of forming intermolecular disulfide bond and exist as a dimer when treated with H2O2. Overproduction of Alr2205 in E. coli protected cells from heavy metals, but not oxidative stress. To delve into its physiological role, Alr2205/Alr2205C41S was overexpressed in Anabaena, and the ability of the corresponding strains (An2205+ or An2205C41S+) to withstand environmental stresses was assessed. An2205+ showed higher resistance to H2O2 than An2205C41S+, indicating that the disulfide reductase function of this protein was critical to protect cells from this peroxide. Although, An2205+ did not show increased capability to withstand cadmium stress, An2205C41S+ was more susceptible to this heavy metal. This is the first study that provides a vital understanding into the function of atypical thioredoxins in countering the toxic effects of heavy metals/H2O2 in prokaryotes.
Subject(s)
Anabaena , Cyanobacteria , Peroxiredoxins/genetics , Peroxiredoxins/metabolism , Hydrogen Peroxide/metabolism , Cysteine/genetics , Cysteine/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Oxidation-Reduction , Bacterial Proteins/metabolism , Anabaena/genetics , Anabaena/metabolism , Cyanobacteria/metabolism , Thioredoxins/chemistry , Disulfides/metabolism , Thioredoxin-Disulfide Reductase/genetics , Thioredoxin-Disulfide Reductase/metabolismABSTRACT
BACKGROUND: Rhino-orbital-cerebral mucor mycosis (ROCM) is a relatively rare opportunistic infection caused by the Mucorales species. While ROCM suggests involvement of the paranasal sinuses, orbit and brain ROM (rhino-orbital-Mucormycosis) stands for the fungal invasion in sinuses and orbit sans cerebral involvement. In India with the outbreak of the second COVID wave and the delta variant of the virus, there has been a steep increase in this opportunistic fulminant fungal infection, named COVID-associated Mucor mycosis (CAM). The most critical question in orbital management is when to go ahead with an exenteration. Our study aims to design a pertinent minimal invasive surgical protocol for surgeons to manage such cases based on our surgical experience and mitigate the need for exenteration and save the eyes wherever possible. METHODS: The study is a retrospective analysis of patients of ROM with and without brain involvement, who underwent minimal surgical management between March 2021 to March 2022 along with their follow-up. RESULTS: There were 184 eyes of 148 patients diagnosed with CAM. The mean age was 51.7 years with a male predominance of 103 (70%). All patients developed ROM following the COVID-19 infection and the duration between diagnosis of COVID-19 and ROM was 36 ± 23 days. 18 cases (12%) were bilateral. 76 eyes (41%) had no vision at the presentation. Imaging revealed paranasal sinus involvement (100%), orbital apex involvement (61%), cavernous sinus involvement (53%), and central nervous system (CNS) involvement (47%). All the patients (100%) were treated with systemic Liposomal amphotericin-B and sinus debridement. Endoscopic debridement of the orbital disease was performed in 45 (30.4%) cases, 15(8.1%) eyes underwent exenteration and were later rehabilitated with a customized ocular prosthesis, 103 (56%) eyes underwent transcutaneous retrobulbar amphotericin-B. At a mean follow-up of 13.1 months; the complete resolution was seen in 25 (17%) cases, the residual stable lesion was seen in 77(52%) of the cases and new lesions were developed in 13(9%) of the cases. Mortality was seen in 33 (22%) patients and all of them had CNS involvement. CONCLUSIONS: Systemic and protocol-based management can save the life and salvage the eyes.
Subject(s)
COVID-19 , Eye Infections, Fungal , Mucormycosis , Orbital Diseases , Humans , Male , Middle Aged , Female , Amphotericin B/therapeutic use , Mucormycosis/complications , Mucormycosis/therapy , Mucormycosis/diagnosis , Antifungal Agents/therapeutic use , Retrospective Studies , Eye Infections, Fungal/diagnosis , Eye Infections, Fungal/microbiology , Eye Infections, Fungal/therapy , COVID-19/complications , SARS-CoV-2 , Orbital Diseases/etiology , Orbital Diseases/therapy , Orbital Diseases/diagnosisABSTRACT
Alzheimer's disease (AD) is a major neurodegenerative disease, affecting more than two third cases of dementia in the world. Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used antiinflammatory analgesic agents representing 7.7% of worldwide prescriptions of which 90% are in patients over 65 years old. Based on mixed findings a systematic review and metaanalysis were conducted to develop a better understanding of the protective role of NSAIDs in AD. We used three database PubMed, Web of Science, and Embase to identify the literatures. The studies following cohort and casecontrol design were investigated separately to check the effect of NSAIDs on AD, by the using their fundamental indicators (relative risk and odds ratio). The fixed effect or random effects model were used to estimate the pooled relative risk and pooled odds ratio separately for both the study design, based on magnitude of heterogeneity. A total of 14 studies were selected for metaanalysis. Eight studies were following cohort study design, whereas, six studies were following casecontrol study design. In metaanalysis of cohort studies, the pooled relative risk was 0.67 with 95% C.I 0.39 to 1.15, which was statistically insignificant. In metaanalysis of casecontrol studies, the pooled odds ratio was 0.71 with 95% C.I 0.46 to 1.10, which was statistically insignificant. NSAIDs do not act as a protective factor for Alzheimer's disease. Additionally, methodologically sound randomized controlled trials are required to produce a robust result.
Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Humans , Aged , Alzheimer Disease/drug therapy , Case-Control Studies , Cohort Studies , Anti-Inflammatory Agents, Non-Steroidal/therapeutic useABSTRACT
Objectives A number of regulatory and accrediting bodies require the reporting of critical results on a timely basis (immediately or within the time frame established by the laboratory) to "the responsible, licensed caregiver" as timely notification of critical laboratory results can pivotally affect patient outcome. The aim of the study was to decrease the turnaround time (TAT) of critical result notification along with assurance of notification to the concerned caregiver or clinicians. The objectives was 30% reduction in the critical value notification TAT and identify factors associated with delayed reporting and root cause analysis for these factors by application of quality tools. Materials and Methods The study was conducted at the Institute of Human Behavior and Allied Sciences, Delhi, a tertiary center teaching Hospital, from April 2019 to June 2021. A value streamed Process Map of critical alert was prepared. The incidents related to failure were presented through Pareto chart. The possible causes were analyzed through the fishbone model. The failure mode prioritization was executed with Failure Mode and Effect Analysis (FMEA). Through extensive brainstorming, appropriate and feasible corrective actions were implemented. The effectiveness of the implemented plan was analyzed by reassessing the TAT of critical alert and feedback received by clinical caregivers. Results After implementation of corrective action plan using quality tools for 3 months, the average critical alert TAT was reduced to 21 minutes from 30 minutes (30% reduction). The median critical alert TAT for ICU, emergency, and IPD were reduced to 3 minutes (IQR: 1-7). During the pilot project, 156 critical value data were sent for feedback with treatment plan but was received only for 88 patients (56%). Conclusion Comprehensive utilization of quality tools has a potential role in patient safety by reducing the critical alert TAT as well as establishing an effective communication between laboratory personnel and clinicians.
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AIM AND OBJECTIVES: We compared the effect of different doses of oral folic acid (FA) supplementation (5 mg/day vs. 2.5 mg/day vs. 5 mg/week) on the proportion of children with folate excess (serum folate >20 ng/ml) and plasma homocysteine (Hcys) excess (>15 µmol/l) in transfusion-dependent thalassemia (TDT). MATERIALS AND METHODS: Children with TDT aged 5-18 years received oral FA in doses of 5 mg/day (Group 1), 2.5 mg/day (Group 2) and 5 mg/week (Group 3) for 9 months, after a wash-off period of 8 weeks. Folate levels (Serum and RBC) and plasma Hcys levels were measured after the therapy. RESULTS: Ninety children were randomized to receive one of the three interventions (30 per group). After wash-off period, the median serum folate levels were significantly lower and five children developed folate deficiency; the median [interquartile range (IQR)] serum folate levels (ng/dl) were comparable in the three groups [Group 1: 6.5 (3.3-14.2), Group 2: 5.1 (2.6-10.5) and Group 3: 4.8 (3.4-10.0)]. After 9 months of intervention, the median (IQR) serum folate levels (ng/ml) were comparable in all participants [Group 1: 18.0 (6.5-28), Group 2: 13.5 (6.4-24.5) and Group 3: 9.7 (5.3-22.5); p = 0.11]. Proportion of children with serum folate excess was 40%, 26.7% and 26.7% in Group 1, Group 2 and Group 3 (p = 0.48). Proportion of children with RBC folate excess was 92%, 86.7% and 86.7% in Group 1, Group 2 and Group 3 (p = 0.79). Hyperhomocysteinemia was seen in eight children with no significant difference between median Hcys levels in the groups (p = 0.75). CONCLUSION: Folic acid supplementation is recommended in TDT with 5 mg weekly dose being adequate.
Subject(s)
Folic Acid , Thalassemia , Child , Dietary Supplements , Homocysteine , Humans , Thalassemia/drug therapyABSTRACT
Background and Aims: Ultrasound-guided transversalis fascia plane block (USG-guided TFPB) has recently been evaluated for post-caesarean acute pain management. We compared it with standard wound infiltration for both acute and chronic post-caesarean pain management. Methods: All patients undergoing caesarean section (CS) under subarachnoid block were included and randomised. Patients in group C received standard wound infiltration (20 ml of 0.375% ropivacaine) and group-T received bilateral USG-guided TFPB (20 ml of 0.375% ropivacaine) at the end of the surgery. Acute pain assessed using numeric rating scale (NRS), time to first request of analgesia and total rescue analgesic consumption in 24 hours. The incidence of chronic persistent post-surgical pain (CPSP), neuropathic pain component and quality of life (QoL) were assessed. Fisher's exact test, Chi-square test, unpaired Student's t-test and Mann-Whitney U test were used. Results: Sixty patients were included with 30 in each group. NRS score on rest at 6th and 24th hour and on active movement at 1st hour was significantly decreased in group T. The "time to first request of analgesia" was statistically higher in group T, that is, 10.77 ± 1.39 h versus 6.30 ± 1.60 h. Five (16.6%) and two (6.6%) patients in groups C and T, respectively, required rescue analgesia in first 24 hours. 30% (n = 6) and 10% (n = 2) patients in groups C and T, respectively, developed CPSP. The neuropathic pain component was significantly reduced and QoL was significantly improved in group T. Conclusion: TFPB is efficacious for management of both acute and chronic post-caesarean pain management.
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The TonB-dependent outer membrane (OM) transporters import iron (Fe) under Fe-deficient growth conditions in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 (S. 6803 or WT). The present study characterises the mechanisms employed by a homozygous Δslr1908 (Slr1908, an OM protein) mutant of S. 6803 to adapt to intracellular iron deficiency imposed due to lack of Slr1908 when grown under Fe sufficient conditions for short (1 week) and long term (3 weeks). Although the homozygous Δslr1908 cells showed symptoms of stress such as slow growth, high ROS and altered ultrastructure, they were transcriptionally as well as translationally modulating their physiology to abrogate the Fe limitation. The mutant displayed only 20% of the Fe content in comparison to the WT after 1 week of growth, which increased to 50% by the end of the third week. The increase in intracellular Fe is ascribed to higher transcripts as well as corresponding protein of slr0042 which is the alternate OM route for Fe uptake. The mutant was also allocating its available Fe pools judiciously among Fe requiring proteins such as catalase, superoxide dismutase and cytochromes. The results elucidate the mechanism employed to tide over the Fe deficiency by Δslr1908 mutant and will be important in explaining the fine-tuning of Fe homeostasis in this model cyanobacterium.
Subject(s)
Synechocystis , Adaptation, Psychological , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biological Transport , Iron/metabolism , Membrane Transport Proteins/metabolism , Synechocystis/genetics , Synechocystis/metabolismABSTRACT
PURPOSE: Oxytocin infusions for uterine tone maintenance are recommended following initial low oxytocin doses during cesarean section. Very limited literature is available on the optimal infusion rates in laboring patients who have been earlier exposed to oxytocin. METHODS: 105 patients, having received oxytocin for induction/augmentation of labor, received oxytocin infusions at rates of 2.5 IU/h (Group 2.5), 5 IU/h (Group 5) or 10 IU/h (Group 10) following 3 IU slow bolus. The primary outcome measure was estimated intraoperative blood loss; secondary outcome measures included uterine tone adequacy, requirements for additional uterotonics, and any side effects. Minor postpartum hemorrhage (PPH) was defined as blood loss > 500 ml and major/severe hemorrhage as blood loss > 1000 ml. RESULTS: Group 10 had minimum blood loss (311.1 ± 44.9 ml) and uterotonic requirements compared to other groups (p < 0.001). Group 2.5 had maximum blood loss (549.4 ± 74.3 ml) and uterotonic requirements; Group 5 had intermediate values (402.0 ± 49.5 ml). Twenty-six patients in group 2.5 had minor PPH against only one in group 5 and none in group 10 (p < 0.001). No patient in either group had major PPH. The incidence of hypotension was higher in group 10 than in group 2.5 (p = 0.004). Nausea and vomiting were also more frequent in group 10 than in the other two groups. CONCLUSION: Oxytocin infusions at 5 IU/h and 10 IU/h are more effective in reducing blood loss and preventing PPH than 2.5 IU/h. The dose of 10 IU/h, although the most efficacious, is associated with a high incidence of side effects. Hence, further studies are needed to find out the optimal maintenance infusion rate of oxytocin during cesarean section in laboring patients who have received oxytocin earlier.
Subject(s)
Labor, Obstetric , Oxytocics , Oxytocin , Postpartum Hemorrhage , Cesarean Section , Female , Humans , Oxytocics/administration & dosage , Oxytocin/administration & dosage , Postpartum Hemorrhage/epidemiology , Postpartum Hemorrhage/prevention & control , PregnancyABSTRACT
OBJECTIVE: To find association between fetal urine production rate (FUPR) and fetal inflammatory response syndrome (FIRS) in preterm premature rupture of membranes (PPROM). METHODS: A prospective cohort study of 70 pregnant women with PPROM at 28-34 weeks of pregnancy was conducted. FUPR was calculated by performing serial fetal bladder volume measurements ultrasonographically and was repeated weekly until delivery. After delivery, cord blood interleukin-6 (IL-6) levels were measured. Placental tissue histopathology was performed and neonatal outcomes were noted. RESULTS: Out of 70 recruited patients with PPROM, 44 had evidence of FIRS (62.86%). Mean FUPR at the time of delivery was significantly reduced in neonates with evidence of FIRS compared with the Non-FIRS group (13.89 ± 8.06 ml/h vs. 25.89 ± 4.94 ml/h). Out of 41 patients with reduced FUPR, 39 neonates had FIRS whereas only five out of 29 neonates with normal FUPR had FIRS (P < 0.001). Severe neonatal morbidity was found in 24 out of 41 (58.54%) neonates with reduced FUPR prenatally. The occurrence of respiratory distress syndrome, necrotizing enterocolitis, and sepsis was significantly high in neonates with reduced FUPR. CONCLUSION: Reduced FUPR is strongly associated with FIRS in cases of PPROM and hence can be used as an early predictor of adverse neonatal outcomes.
Subject(s)
Chorioamnionitis , Fetal Membranes, Premature Rupture , Biomarkers , Female , Fetal Diseases , Gestational Age , Humans , Infant, Newborn , Interleukin-6 , Placenta/pathology , Pregnancy , Prospective Studies , Systemic Inflammatory Response SyndromeABSTRACT
Previously, we demonstrated an integrated genomic convergence and network analysis approach to identify the candidate genes associated with the complex neurodegenerative disorder, Alzheimer's disease (AD). Here, we performed a pilot study to validate the in silico approach by studying the association of genetic variants from three identified critical genes, APOE, EGFR, and ACTB, with AD. A total of 103 patients with AD and 146 healthy controls were recruited. A total of 46 single-nucleotide polymorphisms (SNPs) spanning the three genes were genotyped, of which only 19 SNPs were included in the final analyses after excluding non-polymorphic and Hardy-Weinberg equilibrium-violating SNPs. Apart from our previously reported APOE ε4, four other SNPs in APOE (rs405509, rs7259620, -rs769449, and rs7256173), one in EGFR (rs6970262), and one in ACTB (rs852423) showed a significant association with AD (p < 0.05). Our results validate the reliability of genomic convergence and network analysis approach in identifying the AD-associated candidate genes.
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BACKGROUND: Coronaviruses (CoVs) have a neuroinvasive potential, which has been discussed in various research papers. During the current pandemic, the novel CoV, i.e., SARS-CoV-2, is causing a considerable number of fatalities and posing a great danger of a recurrent epidemic. COVID-19 has been labeled as a public health emergency of international concern, and the epidemic curves are on the rise. PURPOSE: Some studies discuss the neurological implications of SARS-CoV-2 but in light of growing number of evidences we cannot ignore the planning of mental health care settings in COVID-19. We are discussing how this novel CoV can affect the human brain directly and indirectly, including psychiatric problems, and how neurological conditions can be explored as a diagnostic tool in COVID-19 by analyzing cohort studies and review papers that discuss the recent neurological findings in COVID-19. METHOD: Current research and review papers were searched to find out any relation between the COVID-19 disease and the altered mental health. This study attempts to find out neurological symptoms in a large population affected by COVID-19 and thus filtering out individual case reports and cohort studies which have a patient pool of less than 50. RESULTS: This unique observation revealed that SARS-CoV-2 has direct neurological manifestations such as anosmia and gustatory impairment, encephalopathy, and seizures as well as an indirect effect on the psychiatric health such as anxiety, amnesia, etc. because of psychosocial stress. CONCLUSION: The most commonly reported neurological symptoms should not be ignored and must be tested for COVID-19. More neurological studies like medical imaging and neuropathology should be performed on these COVID-19 patients.
ABSTRACT
BACKGROUND: Studies comparing phenylephrine and norepinephrine for the treatment of postspinal hypotension in pre-eclamptic patients are limited. OBJECTIVE: To compare bolus doses of phenylephrine and norepinephrine for treating hypotension in pre-eclamptic mothers undergoing caesarean section under spinal anaesthesia. It was hypothesised that norepinephrine and phenylephrine use would be associated with similar neonatal outcome. DESIGN: Randomised controlled study. SETTING: Single centre, tertiary care, university teaching hospital, from December 2018 to March 2020. PATIENTS: A total of 86 women with pre-eclampsia and a singleton pregnancy who developed postspinal hypotension during caesarean section. INTERVENTIONS: Patients received intravenous phenylephrine (50âµg) or norepinephrine (4âµg) for treatment of hypotension, defined as a fall in baseline systolic BP by ≥â20% or an absolute valueâ<â100âmmHg. MAIN OUTCOME MEASURES: The primary outcome was umbilical artery pH. Secondary outcomes included Apgar scores, the number of hypotensive episodes, vasopressor requirements, the incidence of tachycardia/bradycardia/arrhythmias/hypertension and maternal complications. RESULTS: Umbilical artery pH was not different between the phenylephrine and norepinephrine groups (7.26â±â0.06 and 7.27â±â0.06, respectively; Pâ=â0.903). The median [IQR] number of hypotensive episodes was higher in the norepinephrine than the phenylephrine group: 2 [1 to 3] vs 1 [1 to 2], respectively; Pâ=â0.014. Apgar scores, total number of vasopressor boluses required, systolic BP trends and the incidence of maternal complications were comparable in the two groups. Heart rate (HR) values were lower in phenylephrine group (Pâ=â0.026), and one patient in phenylephrine group and none in the norepinephrine group developed bradycardia (HRâ<â50âbpm), Pâ=â1.000. CONCLUSIONS: In women with pre-eclampsia undergoing caesarean section, bolus doses of phenylephrine (50âµg) and norepinephrine (4âµg) used to treat hypotension after spinal anaesthesia are equally effective with similar neonatal and maternal outcomes. TRIAL REGISTRATION: CTRI/2018/11/016478.
Subject(s)
Anesthesia, Obstetrical , Anesthesia, Spinal , Hypotension , Pre-Eclampsia , Anesthesia, Obstetrical/adverse effects , Anesthesia, Spinal/adverse effects , Cesarean Section/adverse effects , Double-Blind Method , Female , Humans , Hypotension/chemically induced , Hypotension/diagnosis , Hypotension/drug therapy , Infant, Newborn , Infusions, Intravenous , Norepinephrine , Phenylephrine , Pre-Eclampsia/diagnosis , Pre-Eclampsia/drug therapy , Pregnancy , Vasoconstrictor Agents/therapeutic useABSTRACT
PURPOSE: The aim of this study was to determine the alteration in ganglion cell complex and its relationship with retinal nerve fiber layer (RNFL) thickness as measured by spectral-domain optical coherence tomography (OCT) in pituitary adenoma cases and also its correlation with visual field (VF). METHODS: This is a prospective comparative study wherein detailed neuro-ophthalmic examination including perimetry, RNFL and ganglion cell layer inner plexiform layer (GCL-IPL) thickness were measured preoperatively in the cases of pituitary adenoma with chiasmal compression with visual symptoms and field changes who were planned for neuro-surgical intervention. These parameters were repeated 1 year after the surgery. GCL-IPL, RNFL parameters were compared with controls and were correlated with VF mean deviation (MD). The diagnostic power of GCL-IPL was tested using the receiver operating characteristic (ROC) curve. Healthy age and sex-matched controls without any ocular and systemic abnormality were taken for comparison. RESULTS: Twenty-four patients qualified the inclusion criteria. A significant thinning of GCL-IPL (P = 0.002) and RNFL (P = 0.039) was noticed in the pituitary adenoma group. GCL-IPL (r = 0.780 P < 0.001) and RNFL (r = 0.669, P < 0.001) were significantly correlated with the MD. The ROC curve values of GCL-IPL were 0.859 (95% confidence interval 0.744% to 0.973) and of RNFL were 0.731 (95% confidence interval 0.585-0.877). The diagnostic ability of GCL-IPL was more as compared to the RNFL analysis, although it was statistically insignificant (P = 0.122). CONCLUSION: GCL-IPL measurements on the OCT are a sensitive tool to detect early anterior visual pathway changes in chiasmal compression for pituitary adenoma patients.
Subject(s)
Pituitary Neoplasms , Humans , Nerve Fibers , Optic Chiasm/diagnostic imaging , Pituitary Neoplasms/complications , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/surgery , Prospective Studies , Retinal Ganglion CellsABSTRACT
PURPOSE: The purpose of the study was to evaluate the corneal biomechanical properties in patients post kidney transplant and to compare them with healthy age-matched control. MATERIALS AND METHODS: In this cross-sectional study, 68 patients with kidney transplant (study group) and 68 healthy individuals (control group) were analyzed with ocular response analyzer measurements. Only the right eye of each participant was assessed for corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc), and Goldmann-correlated intraocular pressure (IOPg). RESULTS: The mean CH in the study group was 9.70 ± 1.62 mmHg which was significantly lower than the control group with the mean CH of 10.60 ± 1.49 mmHg (P = 0.001). The mean IOPcc was 18.17 ± 4.00 mmHg and 16.00 ± 3.94 mmHg in the study and control groups, respectively (P = 0.002). CRF and IOPg were not significantly different between groups. CONCLUSION: CH and IOPccare altered in kidney transplant patients.