Effect of Community-Initiated Kangaroo Mother Care on Fecal Biomarkers of Gut Function in Low Birth Weight Infants in North India : A Randomized Clinical Trial

This individually randomized trial was conducted to estimate the effect of promoting community-initiated Kangaroo Mother Care (ciKMC) in low birth weight (LBW) infants on gut inflammation and permeability. Participants included 200 stable LBW infants (weighing 1,500–2,250 g) in North India enrolled between May and October 2017. The ciKMC intervention included promotion and support of continuous skin-to-skin contact and exclusive breastfeeding through home visits. The mothers in the intervention arm were supported to practice ciKMC until 28 days after birth, i.e., the neonatal period, or till the baby wriggled out of KMC position, if earlier. Infant stool specimens were collected during the first week of birth, and within 1 week after end of the neonatal period. Concentrations of fecal neopterin (nmol/L), myeloperoxidase (ng/mL), and alpha-1-antitrypsin (μg/mL) were determined using ELISA, and composite enteric enteropathy (EE) score at the end of the neonatal period was calculated by principal component analysis. We did not find any substantial difference in means between the ciKMC and control arm infants in the log-transformed values of neopterin (0.03; 95% CI −0.15 to 0.21), myeloperoxidase (0.28; 95% CI −0.05 to 0.61) and alpha-1-antitrypsin (0.02; 95% CI −0.30 to 0.34). The mean (SD) composite EE score was 13.6 (7.5) in the ciKMC and 12.4 (8.3) in the control arm infants, and the adjusted difference in means was, 0.4 (95% CI −1.8 to 2.7). Our findings suggest that the promotion of ciKMC did not affect gut inflammation and permeability in our target population of LBW infants in North India.acceptedVersionPeer reviewe

Co-Expression of DevR and DevRN-Aph Proteins Is Associated with Hypoxic Adaptation Defect and Virulence Attenuation of Mycobacterium tuberculosis

BACKGROUND: The DevR response regulator is implicated in both hypoxic adaptation and virulence of Mycobacterium tuberculosis (M. tb). DevR regulon genes are powerfully induced in vivo implicating them in bacterial adaptation to host control strategies. A better understanding of DevR function will illumine the way for new strategies to control and treat tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: Towards this objective, we used a combination of genetic, microbiological, biochemical, cell biological tools and a guinea pig virulence assay to compare the hypoxic adaptation and virulence properties of two novel M. tb strains, namely, a devR disruption mutant, Mut1, that expresses C-terminal truncated N-terminal domain of DevR (DevR(NTD)) as a fusion protein with AphI (DevR(N)-Kan), and its complemented strain, Comp1, that expresses intact DevR along with DevR(N)-Kan. Comp1 bacteria exhibit a defect in DevR-mediated phosphosignalling, hypoxic induction of HspX and also hypoxic survival. In addition, we find that Comp1 is attenuated in virulence in guinea pigs and shows decreased infectivity of THP-1 cells. While Mut1 bacilli are also defective in hypoxic adaptation and early growth in spleen, they exhibit an overall virulence comparable to that of wild-type bacteria. CONCLUSIONS/SIGNIFICANCE: The hypoxic defect of Comp1 is associated to a defect in DevR expression level. The demonstrated repression of DevR function by DevR(N)-Kan suggests that such a knockdown approach could be useful for evaluating the activity of DevRS and other two-component signaling pathways. Further investigation is necessary to elucidate the mechanism underlying Comp1 attenuation

Comprehensive insights into Mycobacterium tuberculosis DevR (DosR) regulon activation switch

DevR regulon function is believed to be crucial for the survival of Mycobacterium tuberculosis during dormancy. In this study, we undertook a comprehensive analysis of the DevR regulon. All the regulon promoters were assigned to four classes based on the number of DevR binding sites (Dev boxes). A minimum of two boxes are essential for complete interaction and their tandem arrangement is an architectural hallmark at all promoters. Initial interaction of DevR with the conserved box is essential for its cooperative binding to adjacent sites bearing low to very poor sequence conservation and is the universal mechanism underlying DevR-mediated transcriptional induction. The functional importance of tandem arrangement was established by analyzing promoter variants harboring Dev boxes with altered spacing. Conserved sequence logos were generated from 47 binding sequences which included 24 newly discovered Dev boxes. In each half site of an 18-bp binding motif, G5 and C7 are essential for DevR binding. Finally, we show that DevR regulon induction occurs in a temporal manner and genes that are induced early are also usually powerfully induced. The information theory-based approach along with binding and temporal expression studies provide us with comprehensive insights into the complex pattern of DevR regulon activation

Spontaneous reduction of prolactinoma post cabergoline withdrawal

Prolactinomas are common pituitary tumors usually highly responsive to dopamine agonists. Around 70-90% of the prolactinomas exhibit decrease in tumor size, though variably with these agents. Uncommonly, there may be little or no shrinkage in pituitary tumor. In the absence of medical therapy, pituitary apoplexy may also result in tumor shrinkage, albeit rarely. We report here a case showing only modest reduction in prolactinoma with cabergoline given for a period of one and a half years. Surprisingly, this tumor showed a 40% reduction in the tumor size 3 months after cabergoline withdrawal in the absence of clinical or radiological evidence of apoplexy

Reticulate pigmentation associated with scarring alopecia in an elderly woman: An unusual manifestation of lichen planus pigmentosus

A 70-year-old woman presented with generalized reticulate pigmentation, scarring alopecia, and few discrete, violaceous plaques over the trunk and forearm. Dermoscopic evaluation of the reticulate plaque showed reticulate hyperpigmentation with multiple telangiectasias, and skin biopsy showed lichenoid interface dermatitis with marked pigment incontinence. Thus, a final diagnosis of poikiloderma due to lichen planus pigmentosus was considered

Spontaneous complete remission of type 1 diabetes mellitus in an adult – review and case report

Type 1 diabetes mellitus (T1DM) is an autoimmune condition that results in low plasma insulin levels by destruction of beta cells of the pancreas. As part of the natural progression of this disease, some patients regain beta cell activity transiently. This period is often referred to as the ‘honeymoon period’ or remission of T1DM. During this period, patients manifest improved glycemic control with reduced or no use of insulin or anti-diabetic medications. The incidence rates of remission and duration of remission is extremely variable. Various factors seem to influence the remission rates and duration. These include but are not limited to C-peptide level, serum bicarbonate level at the time of diagnosis, duration of T1DM symptoms, haemoglobin A1C (HbA1C) levels at the time of diagnosis, sex, and age of the patient. Mechanism of remission is not clearly understood. Extensive research is ongoing in regard to the possible prevention and reversal of T1DM. However, most of the studies that showed positive results were small and uncontrolled. We present a 32-year-old newly diagnosed T1DM patient who presented with diabetic ketoacidosis (DKA) and HbA1C of 12.7%. She was on basal bolus insulin regimen for the first 4 months after diagnosis. Later, she stopped taking insulin and other anti-diabetic medications due to compliance and logistical issues. Eleven months after diagnosis, her HbA1C spontaneously improved to 5.6%. Currently (14 months after T1DM diagnosis), she is still in complete remission, not requiring insulin therapy

Effect of Community-Initiated Kangaroo Mother Care on Postpartum Depressive Symptoms and Stress among Mothers of Low-Birth-Weight Infants: A Randomized Clinical Trial

Importance Approximately 1 in 5 women in low- and middle-income countries experience postpartum depression, and the risk is higher among mothers of low-birth-weight (LBW) infants. Kangaroo mother care (KMC) is effective in improving survival among LBW infants, but the benefits of KMC for mothers are not well described. Objective To estimate the effects of community-initiated KMC (ciKMC) on maternal risk of moderate-to-severe postpartum depressive symptoms and on salivary cortisol concentration, a biomarker of stress. Design, Setting, and Participants This was an unmasked, parallel-group, individually randomized clinical trial. Participants included 1950 mothers of stable LBW infants (weighing 1500-2250 g) in rural and semiurban low-income populations in North India enrolled between April 2017 and March 2018. Data analysis was performed from January to July 2020. Interventions Eligible participants were randomly assigned to the intervention or control group by block randomization. The mothers in the intervention group were supported to practice ciKMC until 28 days after birth or until the infant wriggled out of the KMC position (ie, was no longer staying in the KMC position). The intervention included promotion and support of skin-to-skin contact and exclusive breastfeeding through home visits. Main Outcomes and Measures Postpartum depressive symptoms at the end of the neonatal period were measured using the Patient Health Questionnaire–9, with a score of 10 or higher used to identify moderate-to-severe depressive symptoms. Salivary cortisol concentration was measured in a subsample of 550 mothers before and after breastfeeding on day 28 after birth. Results Of the 1950 participants (mean [SD] age, 23 [3.5] years), outcome assessment was completed for 974 of 1047 participants (93%) in the intervention group and 852 of 903 participants (94%) in the control group. Sixty-four percent of participants (1175 of 1826 participants) belonged to the lowest 3 wealth quintiles. The proportion of mothers with moderate-to-severe postpartum depressive symptoms was 10.8% (95% CI, 8.9%-12.9%; 105 of 974 mothers) in the intervention group vs 13.6% (95% CI, 11.4%-16.1%; 116 of 852 mothers) in the control group. The adjusted relative risk of moderate-to-severe maternal postpartum depressive symptoms was 0.75 (95% CI, 0.59-0.96), or an efficacy of 25%. There was no difference in day-28 salivary cortisol concentration between the ciKMC and control group mothers before or after breastfeeding. The analysis estimated that supporting 36 mothers to perform KMC at home would prevent 1 mother from experiencing moderate-to-severe postpartum depressive symptoms. Conclusions and Relevance These findings suggest that ciKMC practice may substantially reduce the risk of moderate-to-severe maternal postpartum depressive symptoms. This evidence supports KMC as an intervention to be incorporated in essential newborn care programs in low- and middle-income settings

Effect of Community-Initiated Kangaroo Mother Care on Postpartum Depressive Symptoms and Stress Among Mothers of Low-Birth-Weight Infants : A Randomized Clinical Trial

Importance: Approximately 1 in 5 women in low- and middle-income countries experience postpartum depression, and the risk is higher among mothers of low-birth-weight (LBW) infants. Kangaroo mother care (KMC) is effective in improving survival among LBW infants, but the benefits of KMC for mothers are not well described. Objective: To estimate the effects of community-initiated KMC (ciKMC) on maternal risk of moderate-to-severe postpartum depressive symptoms and on salivary cortisol concentration, a biomarker of stress. Design, Setting, and Participants: This was an unmasked, parallel-group, individually randomized clinical trial. Participants included 1950 mothers of stable LBW infants (weighing 1500-2250 g) in rural and semiurban low-income populations in North India enrolled between April 2017 and March 2018. Data analysis was performed from January to July 2020. Interventions: Eligible participants were randomly assigned to the intervention or control group by block randomization. The mothers in the intervention group were supported to practice ciKMC until 28 days after birth or until the infant wriggled out of the KMC position (ie, was no longer staying in the KMC position). The intervention included promotion and support of skin-to-skin contact and exclusive breastfeeding through home visits. Main Outcomes and Measures: Postpartum depressive symptoms at the end of the neonatal period were measured using the Patient Health Questionnaire-9, with a score of 10 or higher used to identify moderate-to-severe depressive symptoms. Salivary cortisol concentration was measured in a subsample of 550 mothers before and after breastfeeding on day 28 after birth. Results: Of the 1950 participants (mean [SD] age, 23 [3.5] years), outcome assessment was completed for 974 of 1047 participants (93%) in the intervention group and 852 of 903 participants (94%) in the control group. Sixty-four percent of participants (1175 of 1826 participants) belonged to the lowest 3 wealth quintiles. The proportion of mothers with moderate-to-severe postpartum depressive symptoms was 10.8% (95% CI, 8.9%-12.9%; 105 of 974 mothers) in the intervention group vs 13.6% (95% CI, 11.4%-16.1%; 116 of 852 mothers) in the control group. The adjusted relative risk of moderate-to-severe maternal postpartum depressive symptoms was 0.75 (95% CI, 0.59-0.96), or an efficacy of 25%. There was no difference in day-28 salivary cortisol concentration between the ciKMC and control group mothers before or after breastfeeding. The analysis estimated that supporting 36 mothers to perform KMC at home would prevent 1 mother from experiencing moderate-to-severe postpartum depressive symptoms. Conclusions and Relevance: These findings suggest that ciKMC practice may substantially reduce the risk of moderate-to-severe maternal postpartum depressive symptoms. This evidence supports KMC as an intervention to be incorporated in essential newborn care programs in low- and middle-income settings. Trial Registration: Clinical Trials Registry-India Identifier: CTRI/2017/04/008430.publishedVersionPeer reviewe