Reticulocyte Count: The Forgotten Factor in Transfusion Decisions for Extremely Low Birth Weight Infants.

OBJECTIVE: Extremely low birth weight (ELBW) infants often receive transfusions of packed red blood cells (PRBCs). Long-term outcomes of infants treated with liberal versus restricted transfusion criteria have been evaluated with conflicting results. Clinicians incorporate a reticulocyte count (RC) in their transfusion decisions. There is a lack of information on reference ranges for RCs in growing ELBW infants and whether infant's chronologic age or corrected gestational age (GA) generates a specific trend in the RCs. Our aim was to evaluate the levels of RCs obtained from ELBW infants over the course of the initial hospitalization. STUDY DESIGN: A retrospective chart review of ELBW infants treated in the neonatal intensive care unit (NICU) and had RCs performed. We analyzed the RCs to observe trends based on the chronologic age and corrected GA. RESULTS: A total of 738 RCs were analyzed. A positive trend in RCs that reached a peak at 32 to 34 weeks' corrected GA and then experienced a downward trend was observed. CONCLUSION: Our report examines a very common hematologic test that is theoretically helpful but is in need of guidelines concerning the appropriate frequency of testing and its utility in making transfusion decisions in ELBW infants. KEY POINTS: · RCs should help in making transfusion decisions for ELBW infants.. · No current reference ranges for RC in this population.. · No current reference ranges for RC based on GA and postnatal age..

Prevalence and predictors of hypocalcaemia in severe acute malnutrition.

OBJECTIVE: To determine the prevalence and predictors of hypocalcaemia in under-five children (1-59 months) hospitalised with severe acute malnutrition (SAM). DESIGN: A cross-sectional study was designed to determine the prevalence of hypocalcaemia among children hospitalised with SAM. Serum Ca and 25-hydroxycholecalciferol (25-(OH)D) were estimated. Hypocalcaemia was defined as serum Ca (albumin-adjusted) <2·12 mmol/l. To identify the clinical predictors of hypocalcaemia, a logistic regression model was constructed taking hypocalcaemia as a dependent variable, and sociodemographic and clinical variables as independent variables. SETTING: A tertiary care hospital in Delhi, between November 2017 and April 2019. PARTICIPANTS: One-hundred and fifty children (1-59 months) hospitalised with SAM were enrolled. RESULTS: Hypocalcaemia was documented in thirty-nine (26 %) children hospitalised with SAM, the prevalence being comparable between children aged <6 months (11/41, 26·8 %) and those between 6 and 59 months (28/109, 25·7 %) (P = 0·887). Vitamin D deficiency (serum 25-(OH)D <30 nmol/l) and clinical rickets were observed in ninety-eight (65·3 %) and sixty-three (42 %) children, respectively. Hypocalcaemia occurred more frequently in severely malnourished children with clinical rickets (OR 6·6, 95 % CI 2·54, 17·15, P < 0·001), abdominal distension (OR 4·5, 95 % CI 1·39, 14·54, P = 0·012) and sepsis (OR 2·6, 95 % CI 1·00, 6·57, P = 0·050). CONCLUSION: Rickets and hypocalcaemia are common in children with SAM. Routine supplementation of vitamin D should be considered for severely malnourished children. Ca may be empirically prescribed to severely malnourished children with clinical rickets, abdominal distension and/or sepsis.

Cardiac autonomic tone, plasma BDNF levels and paroxetine response in newly diagnosed patients of generalised anxiety disorder.

Objective: The study examined the effect on cardiac autonomic tone via heart rate variability (HRV), brain derived neurotrophic factor (BDNF) in newly diagnosed generalised anxiety disorder (GAD) cases with paroxetine-controlled release (PX) CR intervention.Methods: Fifty GAD cases using DSM-5 criteria, matched with healthy controls (HC) were assessed with clinical measures (Hamilton Anxiety Scale (HAM-A), Clinical Global Impression- Severity Scale (CGI-Severity), General Health Questionnaire -12 (GHQ-12), HRV, plasma BDNF levels initially and 6 weeks postintervention with paroxetine CR.Results: HRV parameters were significantly lower in GAD vs HC at baseline for standard deviation of normal to normal intervals (SDNN) and proportion of differences in consecutive NN intervals that are longer than 50 ms (pNN50). Significantly higher plasma BDNF levels were noted between HC versus GAD at baseline. Postintervention HAM-A, CGI scores, GHQ-12 item scores showed significant reduction. Significant differences also noted in square root of mean squared difference of successive NN intervals (RMSSD), (SDNN), pNN50 and in plasma BDNF levels after intervention within GAD group. Significant negative correlation observed between HAM-A scores and SDNN parameter after taking PX CR in GAD.Conclusion: GAD showed cardiac autonomic dysfunction, lowered plasma BDNF levels and their improvement with paroxetine CR.Key messageGAD is associated with significantly lower HRV, suggestive of cardiac autonomic dysfunction and lowered plasma BDNF levels, an indicator of stress.Therapeutic intervention with Paroxetine in GAD patients showed clinically significant improvement reflecting restoration of the cardiac autonomic tone and BDNF levels, thus implying their role as potential biomarkers.

CYP2D6*2 Polymorphism as a Predictor of Failed Outpatient Tramadol Therapy in Postherpetic Neuralgia Patients.

Human cytochrome P4502D6 (CYP2D6) gene is highly polymorphic, leading to wide interindividual ethnic differences in CYP2D6-mediated drug metabolism. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of the medication or therapeutic failure with recommended drug dosages. The aim of the study was to find the association of CYP2D6*2 polymorphisms with demographic characters (age, sex, and weight), pain intensity scales [numerical rating scale (NRS) sleep, global perceived effect (GPE)], and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol. The study comprised 246 patients [including 123 nonresponders (NRs) and 123 responders (Rs)] with PHN undergoing analgesic treatment at the pain clinic, Out Patient Department, University College of Medical Sciences, Guru Teg Bahadur Hospital, Delhi, India. Patients with any history of diabetes mellitus, human immunodeficiency virus, malignancy, hematological or liver disease, psychiatric illness, alcohol abuse, and tramadol sensitivity were excluded from the study. The NRSs of (resting and movement), NRS-sleep, and GPE were evaluated by the treating physician. Adverse drug effects during the time of the study were recorded. All samples were analyzed for CYP2D6*2 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution did not vary significantly among genders [NR (P = 0.723); R (P = 0.947)] and different age groups in NRs (P = 0.763) and Rs (P = 0.268). Clinically, statistically significant (P < 0.001) results were obtained in both the groups when compared with baseline in the NRS-sleep and GPE scores, whereas no association was found between NRS-sleep and GPE scores when compared with CYP2D6*2 genotype (P > 0.05). In addition, CYP2D6*2 genotype was not related to the adverse effects of analgesic therapy. The overall results suggested that CYP2D6*2 polymorphism plays no role in the PHN patients receiving tramadol treatment. The CYP2D6*2 polymorphism may not be a predictor of treatment outcome of patients with respect to PHN-receiving tramadol.

Association of organochlorine pesticides with the mRNA expression of tumour necrosis factor-alpha (TNF-α) & cyclooxygenase-2 (COX-2) genes in idiopathic preterm birth.

BACKGROUND & OBJECTIVES: Preterm birth (PTB) is an important cause of prenatal death, neonatal morbidity and mortality and adult illness. Increased inflammation occurs in normal parturition, and inflammatory cytokines and oxidative stress are found to be higher in PTB cases. The present study was planned to investigate the association of organochlorine pesticides (OCPs) with mRNA expression of inflammatory pathway genes such as tumour necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in preterm delivery (PTD) cases. METHODS: Maternal blood samples of PTD (n=30) cases and equal number of term delivery (n=30) were collected at the time of labour. Women occupationally exposed to OCPs and other high risk factors such as anaemia, hypertension, bacterial vaginosis, renal and heart disease, diabetes, etc. were excluded. The OCP levels were estimated by gas chromatography, and mRNA expressions of TNF-α and COX-2 genes were analysed using real-time PCR (qPCR). RESULTS: Significantly higher levels of ß-HCH (beta-hexachlorocyclohexane, 95% CI=2.08-4.633, p0 =0.001), p'p'-DDE (para, para-dichlorodiphenyldichloroethylene, 95% CI=0.546-2.551, p0 =0.003), and o'p'-DDD (ortho, para-dichlorodiphenyldichloroethane, 95% CI=0.004-0.690, P=0.047) were observed in maternal blood of PTB cases as compared to term delivery. The mRNA expressions of COX-2 and TNF-α genes were 3.13 and 2.31 folds higher in PTB cases in comparison to term delivery. l0 inear positive correlations were observed between period of gestation (POG) and ΔCt of COX-2 and TNF-α genes. INTERPRETATION & CONCLUSIONS: Environmental factors such as OCPs may be associated with inflammatory events showing gene-environment interaction in PTB cases. Evaluating the molecular control of inflammation along with gene environment interaction may be used as a model to explore the aetiology of idiopathic PTB cases and may be considered for the prognosis of adverse reproductive outcomes.

Effect of Low Level Subchronic Microwave Radiation on Rat Brain.

OBJECTIVE: The present study was designed to investigate the effects of subchronic low level microwave radiation (MWR) on cognitive function, heat shock protein 70 (HSP70) level and DNA damage in brain of Fischer rats. METHODS: Experiments were performed on male Fischer rats exposed to microwave radiation for 90 days at three different frequencies: 900, 1800, and 2450 MHz. Animals were divided into 4 groups: Group I: Sham exposed, Group II: animals exposed to microwave radiation at 900 MHz and specific absorption rate (SAR) 5.953 × 10-4 W/kg, Group III: animals exposed to 1800 MHz at SAR 5.835 × 10-4 W/kg and Group IV: animals exposed to 2450 MHz at SAR 6.672 × 10-4 W/kg. All the animals were tested for cognitive function using elevated plus maze and Morris water maze at the end of the exposure period and subsequently sacrificed to collect brain tissues. HSP70 levels were estimated by ELISA and DNA damage was assessed using alkaline comet assay. RESULTS: Microwave exposure at 900-2450 MHz with SAR values as mentioned above lead to decline in cognitive function, increase in HSP70 level and DNA damage in brain. CONCLUSION: The results of the present study suggest that low level microwave exposure at frequencies 900, 1800, and 2450 MHz may lead to hazardous effects on brain.

Profile of oxidative stress in response to treatment for type 1 leprosy reaction.

OBJECTIVE: To measure oxidative stress in Type 1 leprosy reaction, and to document the effect of anti-leprosy multidrug therapy (MDT) and anti-reaction drugs on measures of oxidative stress. MATERIALS AND METHODS: A prospective study was carried out at a teaching hospital involving consecutive patients with Type 1 reaction. MDA (malondialdehyde), FRAP (ferric reducing ability of plasma) and GSH (reduced glutathione) were measured in venous blood samples as measures of oxidative stress and compared at inclusion, after 4 weeks of initial therapy (following standard guidelines including MDT, NSAIDS, and systemic steroids), and 4 weeks after clinical remission. RESULTS: The final study cohort included 40 patients with Type 1 reaction (different treatment arms) after excluding for confounding factors such as prior treatment, smoking, NSAID use or concurrent illness requiring therapy. Measures of lipid derived oxidative stress assessed by MDA showed a significant rise with 4 weeks of therapy and a trend towards decline after clinical resolution. In contrast, the other two measures of anti-oxidants namely GSH and FRAP, showed a significant decrease (P < 0.05) at 4 weeks of treatment followed by a significant increase after 4 weeks of clinical remission of reaction. CONCLUSION: MDT and anti-reactional treatment is associated with significant increases in FRAP and GSH levels, reflecting a reduction in the oxidative stress in patients treated for Type 1 reaction. However, lipid peroxidation as measured by MDA is only partially controlled with treatment.

Cognitive impairment and neurogenotoxic effects in rats exposed to low-intensity microwave radiation.

The health hazard of microwave radiation (MWR) has become a recent subject of interest as a result of the enormous increase in mobile phone usage. The present study aimed to investigate the effects of chronic low-intensity microwave exposure on cognitive function, heat shock protein 70 (HSP70), and DNA damage in rat brain. Experiments were performed on male Fischer rats exposed to MWR for 180 days at 3 different frequencies, namely, 900, 1800 MHz, and 2450 MHz. Animals were divided into 4 groups: group I: sham exposed; group II: exposed to MWR at 900 MHz, specific absorption rate (SAR) 5.953 × 10(-4) W/kg; group III: exposed to 1800 MHz, SAR 5.835 × 10(-4) W/kg; and group IV: exposed to 2450 MHz, SAR 6.672 × 10(-4) W/kg. All the rats were tested for cognitive function at the end of the exposure period and were subsequently sacrificed to collect brain. Level of HSP70 was estimated by enzyme-linked immunotarget assay and DNA damage was assessed using alkaline comet assay in all the groups. The results showed declined cognitive function, elevated HSP70 level, and DNA damage in the brain of microwave-exposed animals. The results indicated that, chronic low-intensity microwave exposure in the frequency range of 900 to 2450 MHz may cause hazardous effects on the brain.

Intravenous iron infusions in pediatric patients: A retrospective review of efficacy and safety.

Pediatric iron deficiency anemia (IDA) is often treated with oral iron supplementation as the first-line therapy despite poor adherence. This single-institution retrospective chart review of pediatric patients was conducted to assess the safety, efficacy, and adherence of intravenous (IV) iron infusions compared to oral iron therapy in patients who had failed a trial of oral iron supplementation. We reviewed medical records of patients aged 1-21 with IDA who received at least one IV iron infusion at Cooper University Hospital between 2016 and 2021. Paired t-tests compared pre-infusion and post-infusion hematologic indices of hemoglobin (Hgb), mean corpuscular volume, red blood cell count, red cell distribution width, ferritin, total iron binding capacity, iron stores, and iron saturation. We compared adherence and adverse reactions to both oral iron supplementation and IV iron infusions using McNemar's test. A total of 107 subjects were included (mean age of 12.7 years). Hgb, ferritin, iron, and iron saturation between pre-infusion and post-final infusion significantly improved (p < 0.001). Hgb, ferritin, and iron improved when subcategorizing by race and etiology of IDA. Adherence to IV iron infusions (70.1%) was significantly greater than adherence to oral iron therapy (43.0%). There were also significantly fewer adverse effects with IV iron infusions (3.7%) compared to oral iron (77.9%). We demonstrated the safety, efficacy, and improved adherence of IV iron infusions compared to oral iron supplementation for treatment of pediatric IDA in patients who were unable to tolerate oral iron supplementation. Future studies could compare adherence to multiple doses of IV iron infusions in contrast with other single-dosing IV iron formulations.

Gene-environment interaction in preterm delivery with special reference to organochlorine pesticides.

We investigated the association between glutathione S-transferases mu1 (GSTM1), theta 1 (GSTT1), Cytochrome P450IA1-T6235C (rs4646903, CYP1A1m1) and CYP1A1-1462V (rs1048943, CYP1A1m2) gene polymorphisms, and organochlorine pesticides (OCPs) level with risk of preterm delivery (PTD). Maternal and cord blood samples of PTD (n = 156) cases and subjects of full-term delivery (FTD, n = 151) were collected at the time of delivery/after delivery. Women occupationally exposed to OCPs and other high-risk factors such as anemia, hypertension and dietary habit were excluded. The OCP levels were estimated by gas chromatography, and polymorphic analysis of GSTM1/GSTT1 and CYP450 genes was carried out using multiplex PCR and PCR-restriction fragment length polymorphism, respectively. The frequency of GSTM1/GSTT1 (null) genotype was significantly higher in PTD cases than in the controls. Significantly high levels of α-hexachlorocyclohexane (HCH), γ-HCH and Dichlorodiphenyldichloroethylene (p'p'-DDE) were observed in maternal blood, while significantly high levels of p,p'-dichlorodiphenyltrichloroethane and p'p'-DDE were found in the cord blood of PTD cases compared with the controls. A significant association was seen between ß-HCH and GSTM1 genotype when interaction between GSTM1 gene polymorphism, maternal blood OCP levels and period of gestation (POG) was ascertained. A significant reduction in POG was observed. Similarly, cord blood dieldrin levels were significantly associated with CYP1A1m2 (Aa/aa) with reduction in POG. Our observations indicate that higher levels of OCPs in pregnant women may be associated with increased risk of 'idiopathic' PTD. Furthermore, this study shows that the interaction between high OCPs levels and polymorphism in CYP1A1m2 and GSTM1 null genotypes may magnify the risk of PTD, thus providing evidence for a gene-environment interaction in pregnant women.

Possible role of oxidative stress and brain derived neurotrophic factor in triazophos induced cognitive impairment in rats.

Triazophos, O,O-diethyl-1-H-1,2,4-triazol-3-yl phosphorothioate, (TZ) is an organophosphate pesticide widely used as an insecticide in agriculture fields, however, its adverse effects on cognitive function remain unknown till date. The present study was designed to identify the effect of TZ on cognitive function in order to gain an insight into the molecular mechanism(s) probably involved in TZ induced toxicity. Wistar male albino rats were orally administered with TZ at 8.2 mg/kg bw daily for 30 days. Cognitive function was assessed by evaluating step down latency (SDL) in passive avoidance apparatus, transfer latency (TL) on elevated plus maze and escape latency (EL) using morris water maze. The biochemical changes, in terms of malondialdehyde (MDA), reduced glutathione (GSH) and brain derived neurotrophic factor (BDNF) levels were evaluated in hippocampi regions. Relative mRNA expression and protein expression of BDNF were also evaluated. The results demonstrated that rats treated with TZ showed significantly (p < 0.01) reduced SDL and prolonged TL and EL as compared to control group rats. Moreover, significantly low (p < 0.01) mRNA expression and protein levels (p < 0.001) of BDNF, increased MDA and reduced GSH levels were observed in TZ treated rats. The study concludes that chronic exposure to TZ significantly impairs the learning and memory which may be attributed to the significantly reduced mRNA and protein expression of BDNF in hippocampus. Moreover, BDNF is negatively correlated to MDA levels and positively correlated to GSH levels. Hence, it can be suggested that interplay between BDNF and oxidative stress plays an important role in mediating the toxic effects of TZ.

Safety evaluation and therapeutic efficacy of Habb-e-Asgand, a commonly used antirheumatic polyherbal Unani formulation.

CONTEXT: Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Habb-e-Asgand (HEA) is a polyherbal, Unani formulation widely used in the treatment of RA. Traditional systems of medicine or plant-based drugs are an attractive alternative treatment because of their professed efficacy in curing the disease. Medicinal herbs and herbal formulations are generally considered to be safer than the conventional drugs for RA. Unani drugs are known not to produce toxic effects and are presumed to be nontoxic. However, no objective, verifiable data exists to support the claims of nontoxicity and efficacy. OBJECTIVES: The present study was designed to evaluate the safety and therapeutic efficacy of HEA in Wistar rats. SETTING: The study took place at the University College of Medical Sciences and GTB Hospital, University of Delhi, Dilshad Garden, Delhi, India. DESIGN: Oral toxicity studies--one acute (14 d) and one long-term (90 d)--were carried out using three doses of HEA--57.5, 115, and 230 mg/kg body weight (BWT)--in both male and female rats. The research team also carried out a study on antirheumatic activity. The team induced arthritis in three groups of male rats using collagen type II (CII), and for 20 d, one group was treated once weekly with saline; a second group was treated once weekly with methotrexate (MTX) at 0.25 mg/kg BWT IP; and a third group was treated daily with HEA at 115 mg/kg BWT orally. A control group received saline but was not induced with RA. OUTCOME MEASURES: Rheumatoid factor (RF); anticyclic citrullinated peptide (a-CCP) antibody; antinuclear antibody (ANA); and C-reactive protein (CRP) were measured. RESULTS: The acute and long-term, oral toxicity studies showed that HEA administration did not produce any overt toxicity or mortality and that it was safe at all dose levels tested. No major alterations were observed in hematology, serum biochemistry, necropsy, and histopathology at the therapeutic equivalent dose (ie, 115 mg/kg BWT). HEA administration for 20 d in arthritis-induced rats significantly reduced the levels of autoantibodies and CRP, and the results were comparable with those of MTX, the standard, disease-modifying antirheumatic drug (DMARD). CONCLUSION: The study's results provided evidence that HEA is not toxic at the therapeutic dose. The antiarthritic activity of HEA may be due to its disease-modifying activities, thus supporting the traditional use of this formulation for treatment of RA.

Effect of low level microwave radiation exposure on cognitive function and oxidative stress in rats.

Use of wireless communicating devices is increasing at an exponential rate in present time and is raising serious concerns about possible adverse effects of microwave (MW) radiation emitted from these devices on human health. The present study aimed to evaluate the effects of 900 MHz MW radiation exposure on cognitive function and oxidative stress in blood of Fischer rats. Animals were divided into two groups (6 animals/group): Group I (MW-exposed) and Group II (Sham-exposed). Animals were subjected to MW exposure (Frequency 900 MHz; specific absorption rate 8.4738 x 10(-5) W/kg) in Gigahertz transverse electromagnetic cell (GTEM) for 30 days (2 h/day, 5 days/week). Subsequently, cognitive function and oxidative stress parameters were examined for each group. Results showed significant impairment in cognitive function and increase in oxidative stress, as evidenced by the increase in levels of MDA (a marker of lipid peroxidation) and protein carbonyl (a marker of protein oxidation) and unaltered GSH content in blood. Thus, the study demonstrated that low level MW radiation had significant effect on cognitive function and was also capable of leading to oxidative stress.

A randomized, prospective study of efficacy and safety of oral tramadol in the management of post-herpetic neuralgia in patients from north India.

OBJECTIVE: To evaluate the safety and efficacy of oral tramadol therapy (50 to 200 mg/day) in the treatment for post-herpetic neuralgia (PHN). METHODS: The study was a prospective, single-blind, non-responder vs. responder, randomized trial conducted in 100 outpatients of PHN after oral administration of tramadol for 4 weeks. Those patients who had achieved 50% or greater pain relief after 14 days of oral tramadol treatment were categorized as responders and those reporting < 50% pain relief were categorized as non-responders. Rescue analgesia was provided by the topical application of a cream consisting of the combination of 3.33% doxepin and 0.05% capsaicin to the affected areas of PHN patients of both groups for at least 14 days, along with tramadol therapy. The rescue analgesia was extended to 4 weeks in patients of the non-responder group. The primary endpoints were measured using a numerical rating scale (NRS) at rest and with movement. Secondary endpoints included additional pain ratings such as global perceived effect (GPE), Neuropathic Pain Symptom Inventory scores (NPSI), daily sleep interference score (DSIS), quality of life (QOL) as per WHO QOL-BREF Questionnaire scores, patient and clinician ratings of global improvement. The 2 groups were compared on the basis of pain intensity scores, encompassing primary as well as secondary endpoints, and QOL after 28 days of the treatment regimen. RESULTS: Pain intensity scores measured by NRS (at resting and with movement), NPSI, and DSIS were consistently reduced (P < 0.001) over 28 days at varying intervals in both the groups, but the magnitude of reduction was higher in responders than non-responders. A concomitant improvement (P < 0.001) was observed in GPE on days 3, 14, and 28 as compared to the respective baseline scores in both the groups. Although the WHO QOL-BREF scores showed significant (P < 0.001) improvement in QOL of PHN patients at days 14 and 28 in both the groups, the magnitude of improvement was higher in responders as compared to non-responders. Significant improvement in pain intensity scores and QOL in non-responders is mainly attributed to the use of rescue analgesia for 28 days rather than recommended tramadol therapy. CONCLUSIONS: Treatment with tramadol 50 to 200 mg per day was associated with significant pain reduction in terms of enhanced pain relief, reduced sleep interference, greater global improvement, diminished side-effect profile, and improved QOL in PHN patients from North India. Further categorization of PHN patients may be helpful so that additional or alternative therapy may be prescribed to non-responders.

Detection of Low Level Microwave Radiation Induced Deoxyribonucleic Acid Damage Vis-à-vis Genotoxicity in Brain of Fischer Rats.

BACKGROUND: Non-ionizing radiofrequency radiation has been increasingly used in industry, commerce, medicine and especially in mobile phone technology and has become a matter of serious concern in present time. OBJECTIVE: The present study was designed to investigate the possible deoxyribonucleic acid (DNA) damaging effects of low-level microwave radiation in brain of Fischer rats. MATERIALS AND METHODS: Experiments were performed on male Fischer rats exposed to microwave radiation for 30 days at three different frequencies: 900, 1800 and 2450 MHz. Animals were divided into 4 groups: Group I (Sham exposed): Animals not exposed to microwave radiation but kept under same conditions as that of other groups, Group II: Animals exposed to microwave radiation at frequency 900 MHz at specific absorption rate (SAR) 5.953 × 10(-4) W/kg, Group III: Animals exposed to 1800 MHz at SAR 5.835 × 10(-4) W/kg and Group IV: Animals exposed to 2450 MHz at SAR 6.672 × 10(-4) W/kg. At the end of the exposure period animals were sacrificed immediately and DNA damage in brain tissue was assessed using alkaline comet assay. RESULTS: In the present study, we demonstrated DNA damaging effects of low level microwave radiation in brain. CONCLUSION: We concluded that low SAR microwave radiation exposure at these frequencies may induce DNA strand breaks in brain tissue.

Spherocytosis in Newborn Secondary to Novel Heterozygous Mutation in SPTB Gene: Case Report.

This case report describes a novel mutation of the SPTB gene as a potential pathogenic cause of spherocytosis. A 3-week-old male presented with clinical and laboratory signs consistent with hemolytic spherocytosis, including jaundice, hyperbilirubinemia, anemia, reticulocytosis, negative Coombs test, no ABO or Rh incompatibility, and a peripheral blood smear notable for numerous spherocytes. His laboratory work demonstrated persistent anemia despite daily folate prompting next-generation sequencing which revealed a novel mutation in the SPTB gene resulting in a nonfunctioning protein product. Correlation of the genetic finding with clinical presentation may help guide management for this and future patients.

Overview of Rheumatoid Arthritis and Scientific Understanding of the Disease.

Rheumatoid arthritis (RA), a chronic inflammatory autoimmune disorder, is characterised by persistent synovial inflammation, erosion of bones and cartilage, leading to joint destruction. Clinical manifestations are morning stiffness, pain in shoulder, neck and pelvic girdle, loss of mobility with fever, fatigue, malaise, loss of body weight, and development of rheumatoid nodules. Environmental and genetic factors are important contributors in its susceptibility. Association between RA and diet, cigarette smoking, hormones, alcohol, microbiota, infection, and coffee have also been reported. To diagnose patients with RA, American college of rheumatology (ACR, 2010) criteria, developed by European league against rheumatism (EULAR). Inflammation produced in RA patients is due to cell-mediated immune response. The rheumatoid synovium consists of a large number of CD4+ T cells suggesting pathogenic nature of T cells in this disorder. B-cells may also participate in the pathogenesis by several means such as autoantibodies, by instigation of T-cells through expression of co-stimulatory molecules, by generating pro-inflammatory and anti-inflammatory cytokines and by organisation of other inflammatory cells. The conventional management of RA usually focuses over reducing pain and limiting the disability by medical therapies which include a number of classes of agents such as non-steroidal anti-inflammatory drugs (NSAIDs), non-biological and biological agents, disease-modifying anti rheumatic drugs (DMARDs), immunosuppressants, and corticosteroids. However, only proper rehabilitation can promote the objective to achieve the joint functionality and ease of motion which improves independence as well as quality of life in patient suffering from Rheumatoid Arthritis.

Divulging the Intricacies of Crosstalk Between NF-kB and Nrf-2/Keap1 Pathway in the Treatment of Arthritis by Dimethyl Fumarate.

The aim of this study was to examine the hypothesis that use of dimethyl fumarate (DMF) may mitigate arthritic symptoms in collagen-induced arthritis (CIA) rats through activation of NF-E2-related factor 2(Nrf-2) and suppression of NF-kB pathway. Arthritis in rats was induced by subcutaneous injection of collagen type II (200 µl) at the base of the tail. After induction arthritic rats were treated with DMF (25 mg/kg b.wt.) for 20 days from the day 25th to 45th. At the end of the study, serum and joint homogenate was used to assess the oxidative stress and cytokines level. In addition, mRNA expression of various genes such as NF-kB, Keap-1 (Kelch-like ECH-associated protein 1) and Nrf-2 was assayed through qRT-PCR in joint tissue. Finally, all these biochemical and molecular results were confirmed by histological and in silico study. Our results showed that decrease in the clinical severity, inflammation, and cell necrosis in DMF-treated rats. This was related with decrease in NF-kB activity and increase in activity of Nrf-2. Treatment with DMF increases the levels of endogenous antioxidant biomarkers glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and decreases inflammation. These biochemical and molecular results were further confirmed by performing in silico study that shows DMF strongly inhibits the activation of NF-kB, and conversely at the same time increases the activity of Nrf-2 that means a significantly lower amount of inflammatory mediators and oxidants was produced. Decrease in inflammation leads to preserving the joint architecture and alleviation from clinical symptoms of arthritis. Collectively, these results indicate that Nrf-2 activation protects against arthritic symptoms.

COVID-19 Antibody Response in Patients with Thalassemia.

Background The coronavirus disease 2019 (COVID-19) can severely affect people with comorbidities such as those with diabetes, hypertension, chronic lung disease, cancer, and hemoglobinopathies. Studies assessing the clinical characteristics and immune response to COVID-19 infection in patients with thalassemia are limited. Objectives The primary objective of the study was to study the clinical pattern and the immunoglobulin G (IgG) antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with transfusion-dependent thalassemia (TDT) compared to patients without thalassemia. The secondary objective wasto study the relationship of COVID-19 severity with IgG antibody titers. Setting, Design, and Participants This case-control study was conducted at a tertiary care hospital between January 2021 and August 2022. A total of 30 patients with TDT (mean age: 12.7 years, SD: 4.7) and 30 patients without thalassemia (mean age: 13.9 years, SD: 7) who tested positive for COVID-19 in the preceding six weeks were recruited. Methods Serum samples from the cases and controls were collected after 6, 12, and 24 weeks of COVID-19 infection for IgG antibody estimation using chemiluminescent immunoassay. Outcome variables The primary variable was comparative analysis of antibody levels and clinical profile of COVID-19 in cases and controls. The secondaryvariable was association of the severity of COVID-19 with the antibody titers produced. Results Symptomatic individuals among cases (n=12) were significantly lesser than controls (n=22) (p=0.009). The median IgG titers of cases and controls were comparable at six weeks (p=0.40), but the titers were significantly lower for cases at 12 weeks (p=0.011) and 24 weeks (p=0.006). There was significant fall in titers from 6 to 12 and 24 weeks in both the groups. The titers were not affected by COVID-19 severity and pre-existing comorbidities. Conclusion Patients with TDT manifest with mild or asymptomatic COVID-19 and mount a comparable IgG antibody response to COVID-19 akin to controls. However, this serological response could not sustain over three to six months advocating the need for protection through vaccination.

Serological Response to COVID-19 and Its Association With Measles-Rubella (MR)-Containing Vaccines.

BACKGROUND AND OBJECTIVES:  Epidemiological studies suggest that coronavirus disease 2019 (COVID-19) has a less severe disease course and a more favorable prognosis among children. Childhood vaccines and heterologous immunity have been suggested as reasons for this. Additionally, the structural similarity between the measles, rubella, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus particles may affect immune responses. The objective of this study was to compare COVID-19 antibody titers and disease severity between measles-rubella (MR) vaccinated and unvaccinated children. Additionally, we aimed to evaluate and compare the antibody response in recipients of a single dose and two doses of the MR vaccine. METHODS:  The study was prospective and comparative and included 90 COVID-19-positive children aged nine months to 12 years. The study was registered under the clinical trials registry of India (CTRI/2021/01/030363). COVID-19 antibody titers were measured at two weeks, six weeks, and 12 weeks, along with the assessment of MR antibody titers. COVID-19 antibody titers and disease severity were compared between MR-vaccinated and MR-unvaccinated children. The comparison of COVID-19 antibody titers between recipients of a single dose and two doses of MR vaccine was also conducted. RESULTS: The results showed significantly higher median COVID-19 antibody titers at all time points during follow-up in the MR-vaccinated group (P<0.05). However, the two groups had no significant difference in the disease severity. Moreover, there was no difference in the antibody titers of MR one dose and two dose recipients. CONCLUSION: Exposure to even a single dose of MR-containing vaccine enhances the antibody response against COVID-19. However, randomized trials are necessary to further explore this subject.