New insights from the genetic work-up in early onset nephrotic syndrome: report from a registry in western India.

BACKGROUND: Eighty-five percent of infants with congenital nephrotic syndrome (CNS) and 66% with infantile NS (INS) are likely to have a monogenic etiology. There exists a significant genetic variability between different regions and ethnic groups. This study aimed to determine the genetic defects in children with CNS and INS by establishing a registry in western India. METHODS: In this cross-sectional study, pediatric nephrologists from 13 private and government institutions shared relevant clinical data and details of the genetic evaluation of children presenting with NS within the first year of life. RESULTS: The median age at presentation was 9 months (range 1-23, IQR 3-13 months), history of consanguinity between parents existed in 14 patients (34%), family history of similar illness in 6 (15%), and extra-renal manifestations in 17 (41%). Twenty-five (61%) were confirmed to have a monogenic etiology. NPHS1 gene was the most implicated (9/25) followed by PLCE1 (5/25). There were 12 variants of uncertain significance (VUS) involving 10 genes (10/25, 40%), and no definite genetic abnormality was found in 4 (25%). A re-analysis of these VUS attempted 2-3 years later facilitated reclassification of 7/12 (58%); increasing the diagnostic yield from 61 to 68.2%. CONCLUSIONS: Consistent with worldwide data, variants in NPHS1 gene were the most common cause of NS in infancy; however, PLCE1 was implicated more frequently in our cohort. NUP93 and COL4A3 were reported in early onset NS for the first time. Reclassification of VUS should be attempted, if feasible, since it may lead to a useful revision of diagnosis.

Comparison of surgical outcomes related to interpositional arthroplasty materials used in patients with temporomandibular joint ankylosis: a systematic review and meta-analysis.

Surgical management of temporomandibular joint (TMJ) ankylosis involves various techniques from which interpositional arthroplasty (IPA) involves using several materials. The objectives of this study were to assess and compare post arthroplasty maximum mouth opening (MMO), symptoms like pain and discomfort in jaw opening and movements, failures such as reankylosis, neurosensory disturbances, and the effect of confounding variables such as age, gender, physiotherapy, etc. The search (conducted in September, 2021) included studies published in English on otherwise healthy individuals (11 months to 88 years) having undergone arthroplasty with a minimum of six months' follow up. We used search engines such as Cochrane database, PubMed, Embase, Scopus, EBSCO host, Pro quest, J gate, Google Scholar, and manual search to include books and grey literature. Randomised clinical (RCT) and non-randomised clinical trials, observational studies, case series and reports meeting the inclusion criteria were selected. Two reviewers (HD and NP) independently extracted the data. Risk of bias was assessed using the Cochrane tool, Rangel checklist, and Joanna Briggs Institute. Data were analysed using RevMan (Version 5.4). Fifty studies with 1524 participants (442 bilateral and 891 unilateral joints) were included; six RCTs, 31 retrospective, 10 prospective, and three case series and reports. Amongst all interpositional materials, the highest increase in mouth opening was seen with dermis fat graft with a mean difference (Pooled MD) being 35.29mm (95% CI [32.36 to 38.22]). Comparison of temporalis myofascial with gap arthroplasty (GA) showed significant increase in MMO (Pooled MD in mm 1.30 95% CI [0.14 to 2.45]). Recurrence was significantly reduced when (IPA) was used, compared with GA (Risk difference 0.08mm 95% CI [-0.15 to -0.02]) and for Temporalis Myofascial Flap (TMF) when compared with GA (Risk difference -0.07mm 95% CI [-0.15 to 0]). Higher odds for developing neurosensory disturbances were seen with Al-Kayat Bramley incision (Pooled OR 0.11 95% CI [0.04 to 0.34]) compared to pre-auricular incision (Pooled OR 0.03 95% CI [0.01 to 0.09]). IPA was superior to GA with respect to maximum mouth opening (MMO) (Pooled MD in mm 1.21 95% CI [0.41 to 2.07]). Dermis fat graft offers the highest MMO. The overall quality of evidence for RCTs is poor while that of observational studies is moderate as per the relevant assessment of quality of evidence. More research with appropriate study designs is needed. Similar to the findings from the previous reviews, outcomes with IPA were superior when compared to GA in terms of mouth opening and less recurrence.

High Dilutions of Drugs show Distinct Variation from each other in their Electronic Spectra

Drugs at high dilution (HD) produce therapeutic effect on man, animals and plants. Experimental evidence shows that free water molecules and hydrogen bond strength of OH groups constitute the physical basis of HDs which are otherwise devoid of original drug molecules. HDs are produced in aqueous EtOH by serial dilution of a substance with mechanical agitation or succussion in each step, and are called potencies. Three potencies 6 cH, 12 cH and 30 cH of two drugs Anacardium orientale and Natrum muriaticum(NaCl) and their mother tincture (MT) are used in this study. Electronic spectra of these MTs and potencies, all in 90% EtOH, were taken in the wavelength region of 190 nm ­350 nm. The objective is to find out any additional physical-chemical entities in potencies besides the aforesaid two factors. It was reported earlier that charge transfer (CT) interaction accompanies potentization of drugs. This study focused on the CT interaction. The results indicate that spectral pattern and absorbance intensities of the test samples vary from each other. Natm 6cH (absorbance 0.30 at 196.53nm), 12cH (abs. 0.06 at 196.53nm) and 30cH (abs. 1.32 at 196.5nm). Anac 6cH (abs. 0.33 at 203nm), 12cH (abs. 0.61 at 208nm) and 30cH (abs. 0.09 at 200.67nm). The spectrum of each potency shows two peaks. The 2nd peak at higher wave length belongs to CT interaction. Anac 6cH suc, 7cH unsuc. Insersections at 197.14nm with abs. 0.05, and 290nm with abs. 0.01. Anac 12cH suc, 13cH unsuc. Intersections at 196.93nm with abs. 0.06, and 273nm with abs. 0.00. Anac 30cH suc, 31cH unsuc. Intersections at 194.42nm with abs. -0.05, 238.03nm with abs. -0.01, 252.15nm with abs. -0.002, and 261nm with abs. 0.004. Natm 6cH suc, 7cH unsuc. Intersection at 199.44nm with Abs -0.11. Natm 12cH suc, 13cH unsuc. Instersection at 200.48nm with abs. -0.11. Natm 30cH suc, 31cH unsuc. Intersection at 204.24nm with abs. -0.08. Potentization involves CT interaction in consecutive potencies. Water and EtOH do not form a homogeneous mixture and have aggregates of EtOHand water molecules. CT interactions occur in these individual aggregates and are mostly inter molecular within EtOH or water. These aggregates vary from each other in the test samples. The spectra of test samples were analysed for margin of error (MOE). The MOE is very small (0.001-0.002%), and for this reason the difference between the spectra is significant. Besides that the intersection between consecutive spectra vary in number and position. It is concluded that water and EtOH aggregates and their relative distribution constitute additional physical-chemical basis of potencies.

COVID-19 in children treated with immunosuppressive medication for kidney diseases.

BACKGROUND: Children are recognised as at lower risk of severe COVID-19 compared with adults, but the impact of immunosuppression is yet to be determined. This study aims to describe the clinical course of COVID-19 in children with kidney disease taking immunosuppressive medication and to assess disease severity. METHODS: Cross-sectional study hosted by the European Rare Kidney Disease Reference Network and supported by the European, Asian and International paediatric nephrology societies. Anonymised data were submitted online for any child (age <20 years) with COVID-19 taking immunosuppressive medication for a kidney condition. Study recruited for 16 weeks from 15 March 2020 to 05 July 2020. The primary outcome was severity of COVID-19. RESULTS: 113 children were reported in this study from 30 different countries. Median age: 13 years (49% male). Main underlying reasons for immunosuppressive therapy: kidney transplant (47%), nephrotic syndrome (27%), systemic lupus erythematosus (10%). Immunosuppressive medications used include: glucocorticoids (76%), mycophenolate mofetil (MMF) (54%), tacrolimus/ciclosporine A (58%), rituximab/ofatumumab (11%). 78% required no respiratory support during COVID-19 illness, 5% required bi-level positive airway pressure or ventilation. Four children died; all deaths reported were from low-income countries with associated comorbidities. There was no significant difference in severity of COVID-19 based on gender, dialysis status, underlying kidney condition, and type or number of immunosuppressive medications. CONCLUSIONS: This global study shows most children with a kidney disease taking immunosuppressive medication have mild disease with SARS-CoV-2 infection. We therefore suggest that children on immunosuppressive therapy should not be more strictly isolated than children who are not on immunosuppressive therapy.