Brain serotonin and serotonin transporter expression in male and female postnatal rat offspring in response to perturbed early life dietary exposures.

Introduction: Serotonin (5-HT) is critical for neurodevelopment and the serotonin transporter (SERT) modulates serotonin levels. Perturbed prenatal and postnatal dietary exposures affect the developing offspring predisposing to neurobehavioral disorders in the adult. We hypothesized that the postnatal brain 5-HT-SERT imbalance associated with gut dysbiosis forms the contributing gut-brain axis dependent mechanism responsible for such ultimate phenotypes. Methods: Employing maternal diet restricted (IUGR, n=8) and high fat+high fructose (HFhf, n=6) dietary modifications, rodent brain serotonin was assessed temporally by ELISA and SERT by quantitative Western blot analysis. Simultaneously, colonic microbiome studies were performed. Results: At early postnatal (P) day 2 no changes in the IUGR, but a ~24% reduction in serotonin (p = 0.00005) in the HFhf group occurred, particularly in the males (p = 0.000007) revealing a male versus female difference (p = 0.006). No such changes in SERT concentrations emerged. At late P21 the IUGR group reared on HFhf (IUGR/HFhf, (n = 4) diet revealed increased serotonin by ~53% in males (p = 0.0001) and 36% in females (p = 0.023). While only females demonstrated a ~40% decrease in serotonin (p = 0.010), the males only trended lower without a significant change within the HFhf group (p = 0.146). SERT on the other hand was no different in HFhf or IUGR/RC, with only the female IUGR/HFhf revealing a 28% decrease (p = 0.036). In colonic microbiome studies, serotonin-producing Bacteriodes increased with decreased Lactobacillus at P2, while the serotonin-producing Streptococcus species increased in IUGR/HFhf at P21. Sex-specific changes emerged in association with brain serotonin or SERT in the case of Alistipase, Anaeroplasma, Blautia, Doria, Lactococcus, Proteus, and Roseburia genera. Discussion: We conclude that an imbalanced 5-HT-SERT axis during postnatal brain development is sex-specific and induced by maternal dietary modifications related to postnatal gut dysbiosis. We speculate that these early changes albeit transient may permanently alter critical neural maturational processes affecting circuitry formation, thereby perturbing the neuropsychiatric equipoise.

Efficacy of Individualized Homeopathic Medicines in the Treatment of Sciatica Pain: Double-Blind, Randomized, Placebo-Controlled Trial.

Objectives: Sciatica is a debilitating condition that causes pain in its distribution or in the lumbosacral nerve root that is connected to it. Although there are claims that homeopathy can reduce sciatica pain, systematic scientific proof is currently lacking. The objective of the trial was to determine whether individualized homeopathic medicines (IHMs) were as effective as identical-looking placebos in treating sciatica pain. Design: This is a double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. Setting: The study was conducted at Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Howrah, West Bengal, India. Subjects: Sixty participants with sciatica pain were included in this study. Interventions: Verum (n = 30; IHMs plus concomitant care) versus control (n = 30; placebos plus concomitant care). Outcome measures: Primary-Sciatica Bothersome Index (SBI) and Sciatica Frequency Index (SFI) scores and secondary-Roland Morris Pain and Disability Questionnaire (RMPDQ), Short Form McGill Pain Questionnaire (SF-MPQ), and Oswestry Low Back Pain Questionnaire (OLBPQ) scores: all of them were measured at baseline, and every month, up to 3 months. Results: Intention-to-treat sample (n = 60) was analyzed. Group differences were examined by two-way (split-half) repeated measure analysis of variance, primarily accounting for between groups and time interactions, and additionally, by unpaired t tests comparing the estimates obtained individually every month. The level of significance was set at p < 0.025 and <0.05 two tailed for the primary and secondary outcomes, respectively. Group differences could not achieve significance in SBI (p = 0.044), SFI (p = 0.080), and RMPDQ scores (p = 0.134), but were significant for SF-MPQ (p = 0.007) and OLBPQ (p = 0.036). Gnaphalium polycephalum (n = 6; 10%) was the most frequently prescribed medicine. No harm, serious adverse events, or intercurrent illnesses were recorded in either of the groups. Conclusions: The primary outcome failed to demonstrate evidently that homeopathy was effective beyond placebo, and the trial remained inconclusive. Independent replications are warranted to confirm the findings. Clinical Trial Registration Number: CTRI/2020/10/028617.

Efficacy of Individualized Homeopathic Medicines in the Treatment of Hemorrhoids: Double-Blind, Randomized, Placebo-Controlled Trial.

Objectives: To investigate the efficacy and safety of individualized homeopathic medicines (IHMs) in treating hemorrhoids compared with placebo. Design: This is a double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. Setting: The trial was conducted at the surgery outpatient department of the State National Homoeopathic Medical College and Hospital, Lucknow, Uttar Pradesh, India. Subjects: Patients were 140 women and men, aged between 18 and 65 years, with a diagnosis of primary hemorrhoids grades I-III for at least 3 months. Excluded were the patients with grade IV hemorrhoids, anal fissure, and fistula, hypertrophic anal papillae, inflammatory bowel disease, coagulation disorders, rectal malignancies, obstructed portal circulation, patients requiring immediate surgical intervention, and vulnerable samples. Interventions: Patients were randomized to Group 1 (n = 70; IHMs plus concomitant care; verum) and Group 2 (n = 70; placebos plus concomitant care; control). Outcome measures: Primary-the anorectal symptom severity and quality-of-life (ARSSQoL) questionnaire, and secondary-the EuroQol 5-dimensions 5-levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS); all of them were measured at baseline, and every month, up to 3 months. Results: Out of the 140 randomized patients, 122 were protocol compliant. Intention-to-treat sample (n = 140) was analyzed. The level of significance was set at p < 0.05 two tailed. Statistically significant between-group differences were elicited in the ARSSQoL total (Mann-Whitney U [MWU]: 1227.0, p < 0.001) and EQ-5D-5L VAS (MWU: 1228.0, p = 0.001) favoring homeopathy against placebos. Sulfur was the most frequently prescribed medicine. No harm or serious adverse events were reported from either of the groups. Conclusions: IHMs demonstrated superior results over placebo in the short-term treatment of hemorrhoids of grades I-III. The findings are promising, but need to be substantiated by further phase 3 trials. Clinical Trial Registration Number: CTRI/2020/03/024342.

Prespecified Homeopathic Medicines in the Prevention of Confirmed and Suspected cases of COVID-19: A Community-based, Double-blind, Randomized, Placebo-Controlled Prophylaxis Trial.

INTRODUCTION: Homeopathic medicines have been used for decades in the prevention and treatment of infectious diseases. However, the preventive efficacy of specific homeopathic medicines in COVID-19 is not well characterised. This study aimed to evaluate the comparative efficacy of prespecified homeopathic medicines in preventing COVID-19. METHODS: A community-based, double-blind, randomized, placebo-controlled trial was conducted on 4,034 participants residing in Ward no. 27 of the Howrah Municipal Corporation in India. Participants were randomized to receive one of three prespecified homeopathic medicines (Influenzinum 30C, Arsenicum album 30C, Anas barbariae hepatis et cordis extractum 200K (Oscillococcinum®) or placebo. The outcomes were the incidence of laboratory-confirmed and suspected cases of COVID-19 during a follow-up period of one month. RESULTS: During the follow-up period, a total of 13 new laboratory-confirmed COVID-19 cases were reported in the study population. Among these, 5 cases in Influenzinum group, 2 cases in Arsenicum album group, 1 case in Oscillococcinum® group, and 5 cases in Placebo group, were reported. On the other hand, number of suspected COVID-19 cases was significantly less in all the three homeopathic medicine groups compared to placebo. The least number of suspected cases reported in the Oscillococcinum® group (aOR: 0.539; 95%CI: 0.401, 0.726), followed by the Arsenicum album (aOR: 0.337; 95%CI: 0.238, 0.475) and Influenzinum (aOR: 0.058; 95%CI: 0.029, 0.114) groups. CONCLUSION: Prespecified homeopathic medicines, particularly Oscillococcinum® and Arsenicum album 30C, may have a role in preventing COVID-19, especially in reducing the incidence of suspected or COVID-19-like respiratory illnesses. However, the result failed to demonstrate a statistically significant difference in the occurrence of confirmed cases of COVID-19 between the study groups. Further research is needed to evaluate the efficacy of these medicines in different populations and settings. TRIAL REGISTRATION: CTRI/2020/09/028122, dt. September 29, 2020.

A Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of Individualized Homeopathic Medicines in Pre-diabetes.

BACKGROUND: Pre-diabetes (PD) contributes importantly to the disease burden worldwide and is a precursor to stroke, cardiovascular diseases, as well as type-2 diabetes mellitus. OBJECTIVE: In this project, the efficacy of individualized homeopathic medicines (IHMs) was explored against placebos in the treatment of PD. METHODS: A 6-month, double-blind, randomized, placebo-controlled trial was conducted at the outpatient departments of a homeopathic medical college and hospital in India. Sixty participants with PD were randomized to receive either IHMs (n = 30) or identical-looking placebos (n = 30). Concomitant care measures were advised to both groups of participants in terms of dietary advice, yoga, meditation and exercise. The primary outcome measures were fasting blood sugar (FBS) and the oral glucose tolerance test (OGTT); the secondary outcome was the Diabetes Symptom Checklist-Revised (DSC-R) score. All the outcomes were measured at baseline and after 3 and 6 months of treatment. Inter-group differences and effect sizes (Cohen's d) were calculated using two-way repeated measures analysis of variance models after adjusting baseline differences using analysis of co-variance on the intention-to-treat data. RESULTS: Between-group differences in FBS were statistically significant, favored IHMs against placebos (F 1,58 = 7.798, p = 0.007) but not for OGTT (F 1,58 = 1.691, p = 0.199). The secondary outcome, DSC-R total score, favoring IHMs significantly compared with placebos (F 1,58 = 15.752, p < 0.001). Calcarea Carbonicum, Thuja occidentalis and Sulphur were the most frequently prescribed medicines. No harm or serious adverse events were recorded from either of the participant groups. CONCLUSION: IHMs produced significantly better results than placebos in FBS and in DSC-R scores but not in OGTT. Independent replications with larger sample sizes are warranted to substantiate the findings. TRIAL REGISTRATION: CTRI/2019/10/021711.

Efficacy of Individualized Homeopathic Medicines in the Treatment of Menopausal Syndrome: Double-Blind, Randomized, Placebo-Controlled Trial.

Objectives: Menopausal symptoms are systemic symptoms that are associated with estrogen deficiency after menopause. Although widely practiced, homeopathy remains under-researched in menopausal syndrome in terms of quality evidence, especially in randomized trials. The efficacy of individualized homeopathic medicines (IHMs) was evaluated in this trial against placebos in the treatment of the menopausal syndrome. Design: Double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. Setting: Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Howrah, West Bengal, India. Subjects: Sixty women with menopausal syndrome. Interventions: Group 1 (n = 30; IHMs plus concomitant care; verum) versus group 2 (n = 30; placebos plus concomitant care; control). Outcome measures: Primary-the Greene climacteric scale (GCS) total score and menopause rating scale (MRS) total score, and secondary-the Utian quality of life (UQOL) total score; all of them were measured at baseline and every month up to 3 months. Results: Intention-to-treat sample (n = 60) was analyzed. Group differences were examined by two-way (split-half) repeated-measure analysis of variance, primarily taking into account all the estimates measured at monthly intervals, and secondarily, by unpaired t tests comparing the estimates obtained individually every month. The level of significance was set at p < 0.025 two-tailed. Between-group differences were nonsignificant statistically-GCS total score (F1, 58 = 1.372, p = 0.246), MRS total score (F1, 58 = 0.720, p = 0.4), and UQOL total scores (F1, 58 = 2.903, p = 0.094). Some of the subscales preferred IHMs significantly against placebos-for example, MRS somatic subscale (F1, 56 = 0.466, p < 0.001), UQOL occupational subscale (F1, 58 = 4.865, p = 0.031), and UQOL health subscale (F1, 58 = 4.971, p = 0.030). Sulfur and Sepia succus were the most frequently prescribed medicines. No harm or serious adverse events were reported from either group. Conclusions: Although the primary analysis failed to demonstrate clearly that the treatment was effective beyond placebo, some significant benefits of IHMs over placebo could still be detected in some of the subscales in the secondary analysis. Clinical trial registration number: CTRI/2019/10/021634.

Double-Blind, Randomized, Placebo-Controlled Trial of Individualized Homeopathic Medicines in Atopic Dermatitis in Adults: A Replication Trial with 6 Months' Follow-up.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing and remitting inflammatory skin disease that can have a significant impact on quality of life. During the last four decades, a rising trend in AD has been observed in India. Homeopathic medicines are claimed to be beneficial in AD; however, convincing research evidence has been lacking. We compared the efficacy of individualized homeopathic medicines (IHMs) against placebos in the treatment of AD. METHODS: In this double-blind, randomized, placebo-controlled trial of 6 months' duration (n = 60), adult patients were randomized to receive either IHMs (n = 30) or identical-looking placebos (n = 30). All participants received concomitant conventional care, which included the application of olive oil and maintaining local hygiene. The primary outcome measure was disease severity using the Patient-Oriented Scoring of Atopic Dermatitis (PO-SCORAD) scale; secondary outcomes were the Atopic Dermatitis Burden Scale for Adults (ADBSA) and Dermatological Life Quality Index (DLQI) - all were measured at baseline and every month, up to 6 months. Group differences were calculated on the intention-to-treat sample. RESULTS: After 6 months of intervention, inter-group differences became statistically significant on PO-SCORAD, the primary outcome (-18.1; 95% confidence interval, -24.0 to -12.2), favoring IHMs against placebos (F 1, 52 = 14.735; p <0.001; two-way repeated measures analysis of variance). Inter-group differences for the secondary outcomes favored homeopathy, but were overall statistically non-significant (ADBSA: F 1, 52 = 0.019; p = 0.891; DLQI: F 1, 52 = 0.692; p = 0.409). CONCLUSION: IHMs performed significantly better than placebos in reducing the severity of AD in adults, though the medicines had no overall significant impact on AD burden or DLQI.

Variation in the Early Life and Adult Intestinal Microbiome of Intra-Uterine Growth Restricted Rat Offspring Exposed to a High Fat and Fructose Diet.

Intra-Uterine Growth Restriction (IUGR) is a risk factor for many adult-onset chronic diseases, such as diabetes and obesity. These diseases are associated with intestinal microbiome perturbations (dysbiosis). The establishment of an intestinal microbiome begins in utero and continues postnatally (PN). Hypercaloric diet-induced dysbiosis is a major driver of childhood obesity. We hypothesized that different postnatal diets superimposed on IUGR will alter the postnatal intestinal microbiome. We compared four experimental rat groups: (1) Ad lib fed regular chow diet pre- and postnatally (CON), (2-3) IUGR induced by maternal caloric restriction prenatally followed postnatally (PN) by either (2) the control diet (IUGR-RC) or (3) High-Fat-high-fructose (IUGR-HFhf) diet, and lastly (4) HFhf ad lib pre- and postnatally (HFhf). Fecal samples were collected from dams and male and female rat offspring at postnatal day 2, 21, and adult day 180 for 16S rRNA gene sequencing. Maternal diet induced IUGR led to dysbiosis of the intestinal microbiome at PN21. Postnatal HFhf diet significantly reduced microbial diversity and worsened dysbiosis reflected by an increased Gammaproteobacteria/Clostridia ratio. Dysbiosis arising from a mismatch between IUGR and a postnatal HFhf diet may contribute to increased risk of the IUGR offspring for subsequent detrimental health problems.

Efficacy of individualized homeopathic medicines in primary dysmenorrhea: a double-blind, randomized, placebo-controlled, clinical trial.

OBJECTIVES: Homeopathic treatment is claimed to be beneficial for primary dysmenorrhoea (PD); still, systematic research evidences remain compromised. This study was undertaken to examine the efficacy of individualized homeopathic medicines (IH) against placebo in the treatment of PD. METHODS: A double-blind, randomized, placebo-controlled trial was conducted at the gynecology outpatient department of Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, West Bengal, India. Patients were randomized to receive either IH (n=64) or identical-looking placebo (n=64). Primary and secondary outcome measures were 0-10 numeric rating scales (NRS) measuring intensity of pain of dysmenorrhea and verbal multidimensional scoring system (VMSS) respectively; all measured at baseline, and every month, up to 3 months. Group differences and effect sizes (Cohen's d) were calculated on intention-to-treat (ITT) sample. RESULTS: Groups were comparable at baseline (all p>0.05). Attrition rate was 10.9% (IH: 7, placebo: 7). Differences between groups in both pain NRS and VMSS favoured IH over placebo at all time points (all p<0.001, unpaired t-tests and two-ways repeated measures analysis of variance) with medium to large effect sizes. Natrum muriaticum and Pulsatilla nigricans (n=20 each; 15.6%) were the most frequently prescribed medicines. No harms, serious adverse events and intercurrent illnesses were recorded in either of the groups. CONCLUSIONS: Homeopathic medicines acted significantly better than placebo in the treatment of PD. Independent replication is warranted. Trial registration: CTRI/2018/10/016013.

Efficacy of individualized homeopathic medicines in irritable bowel syndrome: A double-blind randomized, placebo-controlled trial.

CONTEXT: Gastrointestinal ailments are some of the common conditions treated in homeopathy; yet only a few trials have explored the effects of individualized homeopathic medicines (IHMs) for irritable bowel syndrome (IBS). OBJECTIVE: To explore the efficacy of IHMs in treatment of IBS. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Outpatient departments of Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, India. PATIENTS: Sixty patients suffering from IBS; randomized to receive either IHMs (n = 30) or identical-looking placebo (n = 30). INTERVENTIONS: IHMs or placebo in the mutual context of concomitant care in terms of dietary advice, yoga, meditation and exercises. MAIN OUTCOME MEASURES: Primary - IBS quality of life (IBS-QOL) questionnaire; secondary -IBS severity scoring system (IBS-SSS) and EQ-5D-5L scores; all measured at baseline and every month, up to 3 months. RESULTS: Group differences and effect sizes (Cohen's d) were calculated on intention-to-treat (ITT) sample. Groups were comparable at baseline. Recruitment, retention and attrition rates were 64.5%, 91.7% and 8.3% respectively. Group differences in IBS-QOL total scores, IBS-SSS, EQ-5D-5L scores favored IHMs against placebo overall and at all the time points (all P < 0.001). Pulsatilla nigricans (n = 4, 6.7%) and Thuja occidentalis (n = 4, 6.7%) were the most frequently prescribed medicines. Barring some minor events unrelated to interventions, no harms or serious adverse events were recorded in either of the groups. Thus, IHMs acted significantly better than placebos in the treatment of IBS. Independent replications are warranted. [Trial registration: CTRI/2019/10/021632].

Plant Extracts as Add-On Therapeutics in Homeopathy: An Open-Label, Randomized Trial Using Mother Tinctures in Prediabetes.

Objectives: Prediabetes is a major public health concern. Different plant extracts are used in homeopathy as mother tinctures (MTs) for the treatment of prediabetes as an adjunct to individualized homeopathic medicines (IHMs); however, their effectiveness remains under-researched. Design: Open-label, randomized (1:1), active-controlled, pragmatic, exploratory trial. Setting: Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Howrah, West Bengal, India. Subjects: Eighty-nine patients with prediabetes. Interventions: Group 1 (n = 45; IHMs plus any one of the following MTs: Cephalandra indica, Gymnema sylvestre, and Syzygium jambolanum; experimental/verum) versus Group 2 (n = 44; IHMs only; control). Outcome measures: Blood parameters, including-the fasting blood sugar (FBS) level, blood sugar level 2 h after ingestion of 75 g of glucose (oral glucose tolerance test [OGTT] result), and glycosylated hemoglobin percentage (HbA1c%), and symptoms, including the Diabetes Symptom Checklist-Revised (DSC-R) score; all of them were measured at baseline and after 3 and 6 months. Results: Although recruitment of 140 patients was initially planned, the target sample size could not be achieved because of coronavirus disease pandemic-related restrictions. Only 89 patients could be enrolled, and the trial had to be terminated prematurely owing to the time constraints of the project. The data of 82 patients (Group 1, n = 40; Group 2, n = 42) were analyzed using a modified intention-to-treat approach. Improvements in all outcomes were greater in Group 1 than in Group 2, but without a significant difference: FBS level (F1, 80 = 4.095, p = 0.046), OGTT result (F1, 80 = 2.399, p = 0.125), HbA1c% (F1, 80 = 1.612, p = 0.208), and DSC-R score (F1, 80 = 0.023, p = 0.880). Conclusions: A promising but nonsignificant trend favored the combination of MTs and IHMs compared with IHMs alone among the patients with prediabetes, especially in FBS. Therefore, further studies are required. Clinical Trial Registration Number: CTRI/2018/08/015319; secondary identifier (UTN): U1111-1218-6016.

Circulating extracellular vesicles exhibit a differential miRNA profile in gestational diabetes mellitus pregnancies.

We undertook a prospective temporal study collecting blood samples from consenting pregnant women, to test the hypothesis that circulating extracellular vesicles (EVs) carrying specific non-coding microRNA signatures can underlie gestational diabetes mellitus (GDM). To test this hypothesis, miRNA cargo of isolated and characterized EVs revealed contributions from the placenta and differential expression at all three trimesters and at delivery between pregnant and non-pregnant states. Many miRNAs originate from the placental-specific chromosome 19 microRNA cluster (19MC) and chromosome 14 microRNA cluster (14MC). Further a positive correlation emerged between third trimester and at delivery EVs containing miRNAs and those expressed by the corresponding post-parturient placentas (R value = 0.63 to 0.69, p value = 2.2X10-16), in normal and GDM. In addition, distinct differences at all trimesters emerged between women who subsequently developed GDM. Analysis by logistic regression with leave-one-out-cross validation revealed the optimal combination of miRNAs using all the circulating miRNAs (miR-92a-3p, miR-192-5p, miR-451a, miR-122-5p), or using only the differentially expressed miRNAs (has-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-100-5p and hsa-miR-125a-3p) in GDM during the first trimester. As an initial step, both sets of miRNAs demonstrated a predictive probability with an area under the curve of 0.95 to 0.96. These miRNAs targeted genes involved in cell metabolism, proliferation and immune tolerance. In particular genes of the P-I-3-Kinase, FOXO, insulin signaling and glucogenic pathways were targeted, suggestive of placental connectivity with various maternal organs/cells, altering physiology along with pathogenic mechanisms underlying the subsequent development of GDM. We conclude that circulating EVs originating from the placenta with their miRNA cargo communicate and regulate signaling pathways in maternal organs, thereby predetermining development of GDM.

Integrated analysis of an in vivo model of intra-nasal exposure to instilled air pollutants reveals cell-type specific responses in the placenta.

The placenta is a heterogeneous organ whose development involves complex interactions of trophoblasts with decidual, vascular, and immune cells at the fetal-maternal interface. It maintains a critical balance between maternal and fetal homeostasis. Placental dysfunction can lead to adverse pregnancy outcomes including intra-uterine growth restriction, pre-eclampsia, or pre-term birth. Exposure to environmental pollutants contributes to the development of placental abnormalities, with poorly understood molecular underpinning. Here we used a mouse (C57BL/6) model of environmental pollutant exposure by administration of a particulate matter (SRM1649b at 300 µg/day/mouse) suspension intra-nasally beginning 2 months before conception and during gestation, in comparison to saline-exposed controls. Placental transcriptomes, at day 19 of gestation, were determined using bulk RNA-seq from whole placentas of exposed (n = 4) and control (n = 4) animals and scRNAseq of three distinct placental layers, followed by flow cytometry analysis of the placental immune cell landscape. Our results indicate a reduction in vascular placental cells, especially cells responsible for structural integrity, and increase in trophoblast proliferation in animals exposed to particulate matter. Pollution-induced inflammation was also evident, especially in the decidual layer. These data indicate that environmental exposure to air pollutants triggers changes in the placental cellular composition, mediating adverse pregnancy outcomes.

Efficacy of Individualized Homeopathic Medicines in Plantar Fasciitis: Double-blind, Randomized, Placebo-Controlled Clinical Trial.

INTRODUCTION: Plantar fasciitis (PF) is a chronic degenerative condition causing marked thickening and fibrosis of the plantar fascia, and collagen necrosis, chondroid metaplasia and calcification. There is little convincing evidence in support of various approaches, including homeopathy, for treating PF. This study was undertaken to examine the efficacy of individualized homeopathic medicines (IHMs) compared with placebo in the treatment of PF. METHODS: A double-blind, randomized, placebo-controlled trial was conducted at the outpatient departments of Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, West Bengal, India. Patients were randomized to receive either IHMs or identical-looking placebo in the mutual context of conservative non-medicinal management. The Foot Function Index (FFI) questionnaire, as an outcome measure, was administered at baseline, and every month, up to 3 months. Group differences (unpaired t-tests) and effect sizes (Cohen's d) were calculated on an intention-to-treat sample. The sample was analyzed statistically after adjusting for baseline differences. RESULTS: The target sample size was 128; however, only 75 could be enrolled (IHMs: 37; Placebo: 38). Attrition rate was 9.3% (IHMs: 4, Placebo: 3). Differences between groups in total FFI% score favored IHMs against placebo at all the time points, with large effect sizes: month 1 (mean difference, -10.0; 95% confidence interval [CI], -15.7 to -4.2; p = 0.001; d = 0.8); month 2 (mean difference, -14.3; 95% CI, -20.4 to -8.2; p <0.001; d = 1.1); and month 3 (mean difference, -23.3; 95% CI, -30.5 to -16.2; p <0.001; d = 1.5). Similar significant results were also observed on three FFI sub-scales (pain%, disability%, and activity limitation%). Natrum muriaticum (n = 14; 18.7%) and Rhus toxicodendron and Ruta graveolens (n = 11 each; 14.7%) were the most frequently prescribed medicines. No harms, serious adverse events, or intercurrent illnesses were recorded in either of the groups. CONCLUSION: IHMs acted significantly better than placebo in the treatment of PF; however, the trial being underpowered, the results should be interpreted as preliminary only. Independent replications are warranted. TRIAL REGISTRATION: CTRI/2018/10/016014.

The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2.

While pregnancy increases the risk for severe COVID-19, the clinical and immunological implications of COVID-19 on maternal-fetal health remain unknown. Here, we present the clinical and immunological landscapes of 93 COVID-19 mothers and 45 of their SARS-CoV-2-exposed infants through comprehensive serum proteomics profiling for >1,400 cytokines of their peripheral and cord blood specimens. Prenatal SARS-CoV-2 infection triggers NF-κB-dependent proinflammatory immune activation. Pregnant women with severe COVID-19 show increased inflammation and unique IFN-λ antiviral signaling, with elevated levels of IFNL1 and IFNLR1. Furthermore, SARS-CoV-2 infection re-shapes maternal immunity at delivery, altering the expression of pregnancy complication-associated cytokines, inducing MMP7, MDK, and ESM1 and reducing BGN and CD209. Finally, COVID-19-exposed infants exhibit induction of T cell-associated cytokines (IL33, NFATC3, and CCL21), while some undergo IL-1ß/IL-18/CASP1 axis-driven neonatal respiratory distress despite birth at term. Our findings demonstrate COVID-19-induced immune rewiring in both mothers and neonates, warranting long-term clinical follow-up to mitigate potential health risks.

Developing Brain Glucose Transporters, Serotonin, Serotonin Transporter, and Oxytocin Receptor Expression in Response to Early-Life Hypocaloric and Hypercaloric Dietary, and Air Pollutant Exposures.

Perturbed maternal diet and prenatal exposure to air pollution (AP) affect the fetal brain, predisposing to postnatal neurobehavioral disorders. Glucose transporters (GLUTs) are key in fueling neurotransmission; deficiency of the neuronal isoform GLUT3 culminates in autism spectrum disorders. Along with the different neurotransmitters, serotonin (5-HT) and oxytocin (OXT) are critical for the development of neural connectivity. Serotonin transporter (SERT) modulates synaptic 5-HT levels, while the OXT receptor (OXTR) mediates OXT action. We hypothesized that perturbed brain GLUT1/GLUT3 regulated 5-HT-SERT imbalance, which serves as a contributing factor to postnatal neuropsychiatric phenotypes, with OXT/OXTR providing a counterbalance. Employing maternal diet restriction (intrauterine growth restriction [IUGR]), high-fat (HF) dietary modifications, and prenatal exposure to simulated AP, fetal (E19) murine brain 5-HT was assessed by ELISA with SERT and OXTR being localized by immunohistochemistry and measured by quantitative Western blot analysis. IUGR with lower head weights led to a 48% reduction in male and female fetal brain GLUT3 with no change in GLUT1, when compared to age- and sex-matched controls, with no significant change in OXTR. In addition, a ∼50% (p = 0.005) decrease in 5-HT and SERT concentrations was displayed in fetal IUGR brains. In contrast, despite emergence of microcephaly, exposure to a maternal HF diet or AP caused no significant changes. We conclude that in the IUGR during fetal brain development, reduced GLUT3 is associated with an imbalanced 5-HT-SERT axis. We speculate that these early changes may set the stage for altering the 5HT-SERT neural axis with postnatal emergence of associated neurodevelopmental disorders.

Compliance to iron-folic-acid supplementation and associated factors among pregnant women: A cross-sectional survey in a district of West Bengal, India.

BACKGROUND: Iron-deficiency anemia is considered to be a major health problem in India. This can complicate a normal pregnancy resulting in poor maternal and fetal outcomes. Iron-folic-acid (IFA) supplementation to antenatal and postnatal mothers given through the National Health Mission (NHM) serves as a major tool to combat this problem. AIM: This study aimed to assess compliance to IFA supplement and associated factors among antenatal mothers in a district of West Bengal, India. METHODS: A cross-sectional observational study was conducted among 208 pregnant mothers attending different subcenters, using multistage sampling technique. Data were collected on their demographic, obstetric profile, compliance to IFA tablets, and knowledge on various health care-related factors through direct interviews. Data were analyzed using SPSS 22.0 (licensed) considering the confidence interval to be 95%. RESULTS: Compliance rate was 81.74%. The most common cause of noncompliance was forgetfulness (73.7%). On multivariate regression analysis, age, history of deworming, and education became the significant predictors for noncompliance to IFA. CONCLUSIONS: Compliance to IFA supplementation was better than the national average, although deworming and education can lead to a better outcome. Health workers played a pivotal role for the success of this national program.

Preparing and Presenting Journal Club Content: An Essential Component of Homeopathic Learning.

Homeopathic education has passed through significant incremental changes in the past few years, where especially postgraduate education has become increasingly slanted toward advanced knowledge of clinical work and research methods. Among many educational activities, a great source of learning is from presenting at or attending a journal club meeting, which is a gathering of people to learn and to critically appraise a journal article or other study material. There has been little previous guidance in homeopathy regarding how to prepare and present journal club content. Selection of a suitable topic is one of the critical prerequisites. Each and every step, from preparation to presentation, needs to be carefully planned and considered. For the meeting to be successful, the final discussion phase requires the active participation and critical insight of all those attending.

Early life high-fat diet exposure maintains glucose tolerance and insulin sensitivity with a fatty liver and small brain size in the adult offspring.

Diet during pregnancy has long lasting consequences on the offspring, warranting a study on the impact of early exposure to a high fat diet on the adult offspring. We hypothesized that a prenatal n-6 enriched diet will have adverse metabolic outcomes on the adult offspring that may be reversed with a postnatal n-3 enriched diet. To test this hypothesis, we examined the adult offspring from three groups: (1) n-6 group: during gestation and lactation, dams consumed an n-6 polyunsaturated fatty acid enriched diet, (2) n-3 group: gestational n-6 diet was followed by an n-3 enriched diet during lactation, and (3) a control (CD) group that received standard diet throughout gestation and lactation. Offspring from all groups weaned to a control diet ad libitum. Beginning at postnatal day 2 (P < .03) and persisting at 360 days in males (P < .04), an increase in hypothalamic AgRP expression occurred in the n-6 and n-3 groups, with an increase in food intake (P = .01), and the n-3 group displaying lower body (P < .03) and brain (P < .05) weights. At 360 days, the n-6 and n-3 groups remained glucose tolerant and insulin sensitive, with increased phosphorylated-AMP-activated protein kinase (P < .05). n-6 group developed hepatic steatosis with reduced hepatic reflected as higher plasma microRNA-122 (P < .04) that targets pAMPK. We conclude that early life exposure to n-6 and n-3 led to hypothalamic AgRP-related higher food intake, with n-6 culminating in a fatty liver partially mitigated by postnatal n-3. While both diets preserved glucose tolerance and insulin sensitivity, postnatal n-3 displayed detrimental effects on the brain.

Role of microRNA-122 in hepatic lipid metabolism of the weanling female rat offspring exposed to prenatal and postnatal caloric restriction.

We examined the role of hepatocyte micro-RNA-122 and hypothalamic neuropeptides, in weanling (21d) female rats exposed to calorie restriction induced growth restriction either prenatally (IUGR), postnatally (PNGR) or both (IPGR) vs. ad lib fed controls (CON). IUGR were hyperinsulinemic, hyperleptinemic and dyslipidemic with high circulating miR-122. In contrast, PNGR and IPGR displayed insufficient glucose, insulin and leptin amidst high ketones with a dichotomy in circulating miR-122 of PNGR