Microbiological Evaluation of Herbal Extracts against Candida albicans in Early Childhood Caries Patients: An In Vitro Study.

Purpose: The current literature proposes a probable role of Candida albicans (C. albicans) in its etiopathogenesis in early childhood caries (ECC). This study aimed to isolate C. albicans species in children with and without ECC and compare the antifungal efficacy of neem, miswak, cinnamon, clove, stevia, and ketoconazole. This study also aimed to assess and compare salivary pH in children with and without ECC. Materials and methods: A total of 60 children were included in the study, who were divided into two groups-group I (children with ECC) and group II (children without ECC). Plaque samples were collected and streaked on Sabouraud dextrose agar (SDA). C. albicans isolates were evaluated, and their susceptibility to herbal agents was tested and compared. Saliva samples were collected, and salivary pH was tested and compared. Results: The presence of C. albicans was significantly higher in group I (76.7%) as compared to group II (23.3%). The mean zone of inhibition for neem was 4.9 mm, whereas, for miswak, it was 4.5 mm; for cinnamon, 9.3 mm; for clove, 3.8 mm; for stevia, 10.9 mm; and for ketoconazole it was 21.09 mm. The mean salivary pH for group I was 6.7, and that for group II was 7.3. Conclusion: Candida albicans (C. albicans) carriage in children with ECC was significantly higher than in children without ECC. All herbal agents showed significant antifungal activity, with stevia showing the highest activity. The average salivary pH of children without ECC was slightly higher than that of children with ECC. How to cite this article: Siddaiah SB, Sinha S, BR A. Microbiological Evaluation of Herbal Extracts against Candida albicans in Early Childhood Caries Patients: An In Vitro Study. Int J Clin Pediatr Dent 2024;17(1):26-30.

Immunohistochemical expression of histone modification pattern in adult glioblastoma.

BACKGROUND: Despite the growing advances in molecular research and therapeutics, glioblastomas are still considered highly invasive aggressive tumors with a median survival of 15 months. Genetic alterations have been studied in detail; however, additionally, there is now growing evidence on the role of epigenetic alterations in glioblastoma. Recently, histone modification patterns have been found to have a significant part in gene expression and prognosis. However, further research in this field is warranted to establish its role for the betterment of these patients with the deadly disease. AIMS: To determine the immunohistochemical expression of histone modifications like histone-3-lysine-18 acetylation (H3K18Ac) and histone-4-lysine 20 trimethylation (H4K20triMe) in glioblastoma patients. MATERIALS AND METHODS: This is a retrospective study of 48 glioblastoma patients who underwent surgery. Immunohistochemistry (IHC) for tri-methyl-histone-H4 (Lys20) (H4K20triMe) and acetyl-histone-H3 (Lys18) (H3K18Ac) was performed in paraffin-embedded tissues manually, and the expression was noted. Data on the mitotic index and overall survival was collected and statistically analyzed. RESULTS: The mean age was 50 years with a M: F ratio of 1.6:1. Out of 48 cases, 60% (28 cases) demonstrated positivity for H3K18Ac and 98% (46 cases) for H4K20triMe. The pattern of expression was nuclear with increased expression adjacent to necrosis and at the invasive front. The overall median Q score for H3K18Ac was 1/12 and for H4K20triMe was 6/12. No significant statistical significance was observed between histone expression, Ki67%, and overall survival. CONCLUSION: Histone modification patterns are being explored in detail in an array of tumors. They also have a potential role in glioblastoma for risk stratification and instituting appropriate treatment based on the prognosis. Epigenetic changes like histone modification patterns, in addition to genetics, can pave the way for a better molecular understanding of glioblastomas and provide hope in the future to improve the survival of these patients with deadly diseases.

Hyponatremia in Guillain-Barre Syndrome: A Review of Its Pathophysiology and Management.

Guillain-Barre syndrome (GBS) is the commonest cause of acute polyradiculoneuropathy that requires hospitalization. Many of these patients experience systemic and disease-related complications during its course. Notable among them is hyponatremia. Though recognized for decades, the precise incidence, prevalence, and mechanism of hyponatremia in GBS are not well known. Hyponatremia in GBS patients is associated with more severe in-hospital disease course, prolonged hospitalization, higher mortality, increased costs, and a greater number of other complications in the hospital and worse functional status at 6 months and at 1 year. Though there are several reports of low sodium associated with GBS, many have not included the exact temporal relationship of sodium or its serial values during GBS thereby underestimating the exact incidence, prevalence, and magnitude of the problem. Early detection, close monitoring, and better understanding of the pathophysiology of hyponatremia have therapeutic implications. We review the complexities of the relationship between hyponatremia and GBS with regard to its pathophysiology and treatment.

Maternal age extremes and adverse pregnancy outcomes in low-resourced settings.

Introduction: Adolescent (<20 years) and advanced maternal age (>35 years) pregnancies carry adverse risks and warrant a critical review in low- and middle-income countries where the burden of adverse pregnancy outcomes is highest. Objective: To describe the prevalence and adverse pregnancy (maternal, perinatal, and neonatal) outcomes associated with extremes of maternal age across six countries. Patients and methods: We performed a historical cohort analysis on prospectively collected data from a population-based cohort study conducted in the Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, and Zambia between 2010 and 2020. We included pregnant women and their neonates. We describe the prevalence and adverse pregnancy outcomes associated with pregnancies in these maternal age groups (<20, 20-24, 25-29, 30-35, and >35 years). Relative risks and 95% confidence intervals of each adverse pregnancy outcome comparing each maternal age group to the reference group of 20-24 years were obtained by fitting a Poisson model adjusting for site, maternal age, parity, multiple gestations, maternal education, antenatal care, and delivery location. Analysis by region was also performed. Results: We analyzed 602,884 deliveries; 13% (78,584) were adolescents, and 5% (28,677) were advanced maternal age (AMA). The overall maternal mortality ratio (MMR) was 147 deaths per 100,000 live births and increased with advancing maternal age: 83 in the adolescent and 298 in the AMA group. The AMA groups had the highest MMR in all regions. Adolescent pregnancy was associated with an adjusted relative risk (aRR) of 1.07 (1.02-1.11) for perinatal mortality and 1.13 (1.06-1.19) for neonatal mortality. In contrast, AMA was associated with an aRR of 2.55 (1.81 to 3.59) for maternal mortality, 1.58 (1.49-1.67) for perinatal mortality, and 1.30 (1.20-1.41) for neonatal mortality, compared to pregnancy in women 20-24 years. This pattern was overall similar in all regions, even in the <18 and 18-19 age groups. Conclusion: The maternal mortality ratio in the LMICs assessed is high and increased with advancing maternal age groups. While less prevalent, AMA was associated with a higher risk of adverse maternal mortality and, like adolescence, was associated with adverse perinatal mortality with little regional variation.

Navigating Tumour Microenvironment and Wnt Signalling Crosstalk: Implications for Advanced Cancer Therapeutics.

Cancer therapeutics face significant challenges due to drug resistance and tumour recurrence. The tumour microenvironment (TME) is a crucial contributor and essential hallmark of cancer. It encompasses various components surrounding the tumour, including intercellular elements, immune system cells, the vascular system, stem cells, and extracellular matrices, all of which play critical roles in tumour progression, epithelial-mesenchymal transition, metastasis, drug resistance, and relapse. These components interact with multiple signalling pathways, positively or negatively influencing cell growth. Abnormal regulation of the Wnt signalling pathway has been observed in tumorigenesis and contributes to tumour growth. A comprehensive understanding and characterisation of how different cells within the TME communicate through signalling pathways is vital. This review aims to explore the intricate and dynamic interactions, expressions, and alterations of TME components and the Wnt signalling pathway, offering valuable insights into the development of therapeutic applications.

Fabrication of 2D+1D nanoarchitecture for transition metal oxide modified CdS nanorods: A comparative study on their photocatalytic hydrogen-generation efficiency.

We report the formation of Mo1-xWxO3-CdS (0 ≤ x ≤1) nanophotocatalysts by a combination of solid-state and solution-impregnation processes. The formation of 2D+1D heterostructured composite was revealed by electron microscopy and the structure of ternary co-catalyst and photocatalysts were confirmed by spectroscopic analyses. The H2evolution activity of the nanocomposites was assessed via photocatalytic splitting of water under the irradiation of visible light. All the nanocomposites studied here exhibit notable catalytic activity and good photostability using lactic acid as the sacrificial electron donor compared to a pristine compound. Among these nanocomposites, WO3-CdS shows superior activity with H2evolution rates of 15.19 mmolg-1h-1, 28 times higher than the pure CdS. The WO3-CdS photoactivity is not only superior among all the composites studied here but also highest among the reported WO3composite catalysts to date. The novel construction of the oxide-based nanocomposite photocatalyst shown here efficiently enhances the catalytic activity by effective separation of charge carriers and inhibits photocorrosion of CdS nanorods. The apparent quantum yield of the hydrogen evolution for WO3-CdS was found to be 8% in the visible spectral range. The disparity of the catalytic ability between MoO3and WO3and the variance among the compositions was unraveled through optical band-offset alignment with respect to CdS. Though the 2D+1D novel fabrication is common to all the composites, the difference in the type of band alignment MoO3(type-I) and WO3(type-II) with CdS plays a highly significant role in the co-catalytic activity.

Examining maternal morbidity across a spectrum of delivery locations: An analysis of the Global Network's Maternal and Neonatal Health Registry.

OBJECTIVE: To better understand maternal morbidity, using quality data from low- and middle-income countries (LMICs), including out-of-hospital deliveries. Additionally, to compare to the WHO estimate that maternal morbidity occurs in 15% of pregnancies, which is based largely on hospital-level data. METHODS: The Global Network for Women's and Children's Health Research Maternal Newborn Health Registry collected data on all pregnancies from seven sites in six LMICs between 2015 and 2020. Rates of maternal mortality and morbidity and the differences in morbidity across delivery location and birth attendant type were evaluated. RESULTS: Among the 280 584 deliveries included in the present analysis, the overall maternal mortality ratio was 138 per 100 000, while 11.7% of women experienced at least one morbidity. Rates of morbidity were generally higher for deliveries occurring within hospitals (19.8%) and by physicians (23.6%). The lowest rates of morbidity were noted among women delivering in non-hospital healthcare facilities (5.6%) or with non-physician clinicians (e.g. nurses, midwives [5.4%]). CONCLUSION: The present study shows important differences in reported maternal morbidity across delivery sites, with a trend towards lower morbidity in non-hospital healthcare facilities and among non-physician clinicians.

Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Down regulation of defensin genes during SARS-CoV-2 infection.

Defensins, crucial components of the innate immune system, play a vital role against infection as part of frontline immunity. Association of SARS-CoV-2 infection with defensins has not been investigated. In this study, we have investigated the expression of defensin genes in the buccal cavity from patients with COVID-19 infection along with negative control samples. Nasopharyngeal/oropharyngeal swab samples collected for screening SARS-CoV-2 infection in early 2020 from Hyderabad, India, were analyzed for the expression of major defensin genes by the quantitative real-time reverse transcription polymerase chain reaction, qRT-PCR. Forty SARS-CoV-2 infected positive and 40 negative swab samples were selected for this study. Based on the qRT-PCR analysis involving gene specific primers for defensin genes, 9 defensin genes were found to be expressed in the nasopharyngeal/oropharyngeal cavity. Four defensin genes were found to be significantly down regulated in SARS-CoV-2 infected patients in comparison with the control samples based on differential expression analysis. The significantly down regulated genes were defensin beta 4A/B, 106B, 107B, and 103A. Down regulation of human beta defensin 2, 3, 6 and 7 suggests that antiviral innate immune response provided by defensins may be compromised in SARS-CoV-2 infection resulting in progression of the disease. Correction of the down regulation process through appropriate defensin peptide-based therapy could be an attractive method of treatment. Keywords: host defense; defensins; COVID-19; gene regulation; SARS-CoV-2.

The Global Network Socioeconomic Status Index as a predictor of stillbirths, perinatal mortality, and neonatal mortality in rural communities in low and lower middle income country sites of the Global Network for Women's and Children's Health Research.

BACKGROUND: Globally, socioeconomic status (SES) is an important health determinant across a range of health conditions and diseases. However, measuring SES within low- and middle-income countries (LMICs) can be particularly challenging given the variation and diversity of LMIC populations. OBJECTIVE: The current study investigates whether maternal SES as assessed by the newly developed Global Network-SES Index is associated with pregnancy outcomes (stillbirths, perinatal mortality, and neonatal mortality) in six LMICs: Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan, and Zambia. METHODS: The analysis included data from 87,923 women enrolled in the Maternal and Newborn Health Registry of the NICHD-funded Global Network for Women's and Children's Health Research. Generalized estimating equations models were computed for each outcome by SES level (high, moderate, or low) and controlling for site, maternal age, parity, years of schooling, body mass index, and facility birth, including sampling cluster as a random effect. RESULTS: Women with low SES had significantly higher risks for stillbirth (p < 0.001), perinatal mortality (p = 0.001), and neonatal mortality (p = 0.005) than women with high SES. In addition, those with moderate SES had significantly higher risks of stillbirth (p = 0.003) and perinatal mortality (p = 0.008) in comparison to those with high SES. CONCLUSION: The SES categories were associated with pregnancy outcomes, supporting the validity of the index as a non-income-based measure of SES for use in studies of pregnancy outcomes in LMICs.

Immunohistochemical expression of beta-catenin in hepatoblastoma and its clinical significance.

Background: Primary hepatic malignancies account for 0.5-2% of all solid tumours in childhood. Hepatoblastoma, a rare embryonic tumour in the general population, represents the most frequent primary hepatic malignancy in the paediatric age group, with an incidence of one new case per million under 15 years of age, median age at diagnosis being 1 year. Aberrant activation of the Wnt/beta-catenin signalling pathway is likely to result in tumorigenesis of hepatoblastoma. The nuclear and intra-cytoplasmic accumulations of beta-catenin correlate with the likely prognosis of the disease. Nuclear expression of beta catenin is associated with a shorter survival, higher stage, and seen in embryonal/undifferentiated types. Aim: To study the expression of beta-catenin in hepatoblastoma by immunohistochemistry and correlate it with the tumour histology and survival outcome. Materials & Methods: This is a retrospective study of 11 children over a period of 5 years with the diagnosis of hepatoblastoma. These children underwent partial hepatectomy or liver transplantation at the Department of Paediatric Surgery. The clinical, histological and survival data were collected. Immunohistochemical analysis with beta-catenin was done and analysed. Results: Mean birth weight of the children was 2.75kg.63.6% had an epithelial type of histology.Beta catenin expression by IHC was studied in 11 cases and found to be positive in 4 cases. Nuclear positivity was noted in 2/4 cases of embryonal type and Cytoplasmic and membranous positivity was seen in the other 2/4 cases. Normal liver showed a membranous pattern of positivity in one case. Negative staining was seen in 6 out of 11 cases. Conclusion: Beta catenin is considered to be an useful tool for assessing the prognosis of patients with hepatoblastoma and its expression is associated with a poor survival outcome. There are no validated biomarkers for prognosis so far. However, larger studies incorporating molecular profiling is warranted to establish prognostic factors for planning effective treatment strategies.

Selective inhibition of miRNA processing by a herpesvirus-encoded miRNA.

Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation1,2. A long appreciated, yet undefined relationship exists between the lytic-latent switch and viral non-coding RNAs3,4. Here we identify viral microRNA (miRNA)-mediated inhibition of host miRNA processing as a cellular mechanism that human herpesvirus 6A (HHV-6A) exploits to disrupt mitochondrial architecture, evade intrinsic host defences and drive the switch from latent to lytic virus infection. We demonstrate that virus-encoded miR-aU14 selectively inhibits the processing of multiple miR-30 family members by direct interaction with the respective primary (pri)-miRNA hairpin loops. Subsequent loss of miR-30 and activation of the miR-30-p53-DRP1 axis triggers a profound disruption of mitochondrial architecture. This impairs induction of type I interferons and is necessary for both productive infection and virus reactivation. Ectopic expression of miR-aU14 triggered virus reactivation from latency, identifying viral miR-aU14 as a readily druggable master regulator of the herpesvirus lytic-latent switch. Our results show that miRNA-mediated inhibition of miRNA processing represents a generalized cellular mechanism that can be exploited to selectively target individual members of miRNA families. We anticipate that targeting miR-aU14 will provide new therapeutic options for preventing herpesvirus reactivations in HHV-6-associated disorders.

Imaging and pathological discordance amongst the plethora of breast lesions in breast biopsies.

INTRODUCTION: Imaging-guided breast tissue biopsy has become an acceptable alternative to open surgical biopsy for nonpalpable breast lesions. Discussion of abnormal results of the correlation between imaging and pathological findings can be very challenging as it can assist in decision-making with regard to the further treatment options by arriving at a comprehensive diagnosis. MATERIALS AND METHODS: This was a retrospective study. Radiological data from imaging-guided breast biopsies of 500 patients during a 6-year period was collected and classified by a specialist radiologist as per the BI-RADS format. Histopathology reports were studied and discordance analyzed. RESULTS: A total of 500 cases were reviewed. Approximately 33% (168) cases fell into the BI-RADS 3 category, 24.4% (122) into the BI-RADS 4, and 37% (187) into BI-RADS 5 categories. Approximately 50% (n = 250) cases were benign, 2.6% (13) belonged to the high-risk category, and 47.4% (237) were malignant. The number of discordant cases was 12 (2.4%), mostly due to technical factors. Sensitivity of biopsies to detect malignancy was 85%, specificity was 96%, and accuracy of biopsy in diagnosing cancer was 90%. DISCUSSION: The "triple assessment" is the most sensitive method for detecting early breast cancer. An effective communication pathway must be established between a clinician, radiologist, and pathologist for surgical excision in discordance as it carries a high prevalence of carcinoma in these lesions. CONCLUSION: In discordant cases, either due to abnormal results of imaging or of abnormal pathological findings, the final decision is based on two concordant findings, out of the three parameters. This involves a multidisciplinary breast conference and an active participation by the pathologist.

What Helping Babies Breathe knowledge and skills are formidable for healthcare workers?

Introduction: Most neonatal deaths occur in the first week of life, due to birth asphyxia. Helping Babies Breathe (HBB), is a simulation-based neonatal resuscitation training program to improve knowledge and skills. There is little information on which knowledge items or skill steps are challenging for the learners. Methods: We used training data from NICHD's Global Network study to understand the items most challenging for Birth Attendants (BA) to guide future curriculum modifications. HBB training was provided in 15 primary, secondary and tertiary level care facilities in Nagpur, India. Refresher training was provided 6 months later. Each knowledge item and skill step was ranked from difficulty level 1 to 6 based on whether 91%-100%, 81%-90%, 71%-80%, 61%-70%, 51%-60% or <50% of learners answered/performed the step correctly. Results: The initial HBB training was conducted in 272 physicians and 516 midwives of which 78 (28%) physicians and 161 (31%) midwives received refresher training. Questions related to timing of cord clamping, management of a meconium-stained baby, and steps to improve ventilation were most difficult for both physicians and midwives. The initial steps of Objective Structured Clinical Examination (OSCE)-A i.e. equipment checking, removing wet linen and immediate skin-to-skin contact were most difficult for both groups. Midwives missed stimulating newborns while physicians missed cord clamping and communicating with mother. In OSCE-B, starting ventilation in the first minute of life was the most missed step after both initial and 6 months refresher training for physicians and midwives. At the retraining, the retention was worst for cutting the cord (physicians level 3), optimal rate of ventilation, improving ventilation & counting heart rate (midwives level 3), calling for help (both groups level 3) and scenario ending step of monitoring the baby and communicating with mother (physicians level 4, midwives 3). Conclusion: All BAs found skill testing more difficult than knowledge testing. The difficulty level was more for midwives than for physicians. So, the HBB training duration and frequency of retraining can be tailored accordingly. This study will also inform subsequent refinement in the curriculum so that both trainers and trainees will be able to achieve the required proficiency.

Desmoplastic ameloblastoma of anterior maxilla - A case report.

The recently recognized desmoplastic ameloblastoma is considered a rare variant of central ameloblastoma. It has been included in the World Health Organization's histopathological typing of odontogenic tumors, similar to benign, locally invasive tumors with low recurrence rate and peculiar histological features, characterized by epithelial changes due to the pressure of stroma on epithelial tissue. The aim of this paper is to report a unique case of desmoplastic ameloblastoma in the mandible of a 21-year-old male with a painless swelling in the anterior region of the maxilla. To our knowledge, only a few cases of adult patients affected by desmoplastic ameloblastoma have been published.

Successful culture of Acanthamoeba remains a key towards diagnosis of unusual clinical presentation of keratitis: A first case report from chhattisgarh.

A fifty-nine-year-old female with corneal ulcer with a history of trauma in the past having clinical presentation of fungal keratitis visited the Ophthalmology outpatient department with a history of redness, watering, pain and white discoloration of the right eye cornea for two months. Sample was cultured on non-nutrient agar medium and revealed Acanthamoeba. Patient was managed with Chlorhexidine eye drop and keratoplasty.

Effects of smoking on oral health: Awareness among dental patients and their attitude towards its cessation.

CONTEXT: Tobacco smoking is the leading cause of preventable premature mortality in the world. Smoking is also detrimental to oral health, causing unaesthetic tooth staining, bad breath, periodontal diseases, impaired healing of wounds, increased risk of dental implant failure, precancerous conditions and oral cancer. AIMS: To assess the awareness of the effects of smoking on oral health among smokers in Mangalore city and to assess the smoker's willingness to quit smoking. SETTINGS AND DESIGN: Cross-sectional study. MATERIAL AND METHODS: Data was collected from 140 participants. A cross sectional study was conducted using a self-administered questionnaire to determine the sociodemographic characteristics, awareness about the effects of smoking on oral health and their willingness to participate in smoking cessation programs and to quit smoking. RESULTS: There was statistically significant difference found in the level of awareness of the smoking effects on oral cancer, on tooth staining and dental implants. However, it was observed that the upper socioeconomic class showed a comparatively higher level of awareness than the other classes. No significant differences were found in the level of awareness of the smoking effects on gum disease and on wound healing. One hundred and thirteen individual out of 140 expressed their willingness to quit smoking and also 78 respondents showed a positive attitude toward participation in cessation programs. CONCLUSION: Participants in this sample had some knowledge about the effects of smoking, but were not much aware of its effect on dental implants, requiring further education.

TOR signaling regulates liquid phase separation of the SMN complex governing snRNP biogenesis.

The activity of the SMN complex in promoting the assembly of pre-mRNA processing UsnRNPs correlates with condensation of the complex in nuclear Cajal bodies. While mechanistic details of its activity have been elucidated, the molecular basis for condensation remains unclear. High SMN complex phosphorylation suggests extensive regulation. Here, we report on systematic siRNA-based screening for modulators of the capacity of SMN to condense in Cajal bodies and identify mTOR and ribosomal protein S6 kinase ß-1 as key regulators. Proteomic analysis reveals TOR-dependent phosphorylations in SMN complex subunits. Using stably expressed or optogenetically controlled phospho mutants, we demonstrate that serine 49 and 63 phosphorylation of human SMN controls the capacity of the complex to condense in Cajal bodies via liquid-liquid phase separation. Our findings link SMN complex condensation and UsnRNP biogenesis to cellular energy levels and suggest modulation of TOR signaling as a rational concept for therapy of the SMN-linked neuromuscular disorder spinal muscular atrophy.

Disorders of sexual differentiation: Report of two rare cases.

Gonadal dysgenesis is a distinct variety of Disorders of Sexual Differentiation (DSD) characterised by incomplete or defective formation of the gonads due to either structural or numerical anomalies of the sex chromosomes or mutations in the genes involved in the development of the gland. Here we present two such rare cases that presented during childhood. Both patients presented with ambiguous genitalia with a 45XO/46XY mosaic chromosome pattern. First case, an infant underwent laparoscopic excision of streak gonad, and a single stage hypospadias repair later. Second case, an adolescent who underwent gonadectomy as a child, presented with a mass which was excised and found to contain uterine and ovarian tissue; second stage hypospadias repair is being planned. Mixed gonadal dysgenesis usually presents with a unilateral testis, a streak gonad on the contralateral side and persistent mullerian structures. The most common karyotype noted is 45XO/46XY. These cases are known to have ambiguous external genitalia. The streak gonads have an increased malignant potential and thus, these patients should be carefully screened and followed up for gonadoblastoma.