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Objectives:This study aims to showcase the complementary nature of utilizing both histopathology and magnetic resonance imaging (MRI) in understanding the otologic pathophysiology of Meniere disease. In addition, it seeks to raise awareness of the value of preserving and curating historical temporal bone collections which continue to inform our understanding of otologic diseases. Methods:The essential anatomical feature of Meniere disease—the distended membranous labyrinth—is explored through a comparison of early temporal bone studies with contemporary MRI techniques. The histopathologic photomicrographs are of inner ear specimens from deceased patients with symptoms consistent with Meniere disease. The MRI sequences from living patients exhibiting classic Meniere disease symptoms during life are captured 4 hours post-administration of gadolinium. Results:Both histopathologic examination and MRI imaging reveal consistent distention of the saccule, utricle, and scala media in patients with Meniere disease. The study shows the histologic photomicrographs of actual Meniere patients compared to the MRIs and successfully demonstrates the correlation between postmortem histological findings and MRI evidence of distension in living patients. Conclusions:A corresponding distension of the membranous labyrinth is seen in both the histologic specimens and the Meniere MRIs. This correlation suggests the potential utility of utilizing MRI to aid in diagnosing atypical Meniere disease and distinguishing it from other disease processes, such as migraine equivalent vertigo. The integration of historical temporal bone studies with modern MRI techniques offers valuable insights into the pathophysiology of otologic diseases. In addition, it emphasizes the importance of preserving and curating historical temporal bone collections for continued research and medical education purposes. Previous studies of delayed MRIs did not use Meniere disease temporal bone histopathology images.

ABSTRACTBackgroundIndia has been implementing active case-finding (ACF) for TB among marginalised and vulnerable (high-risk) populations since 2017. The effectiveness of ACF cycle(s) is dependent on the use of appropriate screening and diagnostic tools and meeting quality indicators.ObjectivesTo determine the number of ACF cycles implemented in 2021 at national, state (n = 36) and district (n = 768) level and quality indicators for the first ACF cycle.MethodsIn this descriptive study, aggregate TB program data for each ACF activity that was extracted was further aggregated against each ACF cycle at the district level in 2021. One ACF cycle was the period identified to cover all the high-risk populations in the district. Three TB ACF quality indicators were calculated: percentage population screened (≥10%), percentage tested among screened (≥4.8%) and percentage diagnosed among tested (≥5%). We also calculated the number needed to screen (NNS) for diagnosing one person with TB (≤1538).ResultsOf 768 TB districts, ACF data for 111 were not available. Of the remaining 657 districts, 642 (98%) implemented one, and 15 implemented two to three ACF cycles. None of the districts or states met all three TB ACF quality indicators’ cut-offs. At the national level, for the first ACF cycle, 9.3% of the population were screened, 1% of the screened were tested and 3.7% of the tested were diagnosed. The NNS was 2824: acceptable (≤1538) in institutional facilities and poor for population-based groups. Data were not consistently available to calculate the percentage of i) high-risk population covered, ii) presumptive TB among screened and iii) tested among presumptive.ConclusionIn 2021, India implemented one ACF cycle with sub-optimal ACF quality indicators. Reducing the losses between screening and testing, improving data quality and sensitising stakeholders regarding the importance of meeting all ACF quality indicators are recommended.

Background : Sex cord and stromal tumors are a heterogeneous group of tumors that arise from gonadal sex cord cells, gonadal stromal cells, or both. They are divided into pure stromal tumors, pure sex cord tumors, and mixed tumors. Some of these tumors are hormonally active, producing androgens and estrogens, and may therefore exhibit virilization or excess estrogen. Sertoli-Leydig cell tumors are rare tumors belonging to mixed tumors representing less than 0.5% of ovarian tumors. Few cases have been reported in the medical literature. Case presentation: We report the case of a 1-year-old girl who was admitted for breast lumps and pubic hair with intermittent painless vaginal bleeding in the past 2 weeks. The abdominal examination objectified the presence of an intraperitoneal mass to which an abdominal ultrasound and computerized tomography (CT) scan had confirmed the presence of a right ovarian mass. A laparoscopy was performed which showed an encapsulated mass arriving from the right ovary replacing the normal ovarian tissue. Laparoscopic-assisted removal of the entire mass was done. The postoperative course was uneventful. The histopathological study demonstrated an intermediately differentiated Sertoli cell tumor with an intact capsule, no lymphovascular invasion, or heterologous elements (TNM stage 1). Conclusions: Although Sertoli-Leydig tumors are commonly seen after the second decade of life in young women, their discovery before puberty is not uncommon. Mass syndrome and signs of virilization are two frequently reported signs that should prompt the clinician to mention this entity among the differential diagnoses. The first-line radiological examination is pelvic ultrasound. The treatment is mainly based on surgery. The prognosis is excellent especially if the tumor is well differentiated.

There is increasing interest and belief in applying quality improvement (QI) to help solve our most complex challenges in healthcare, yet little published literature to help leaders develop a business case and evaluate return on investment from QI. This is even more pronounced in fields such as mental health and community health services. This paper presents a framework to help identify, understand and evaluate return on investment from large-scale application of QI in healthcare providers. The framework has been developed at East London NHS Foundation Trust (ELFT), a provider of predominantly mental health and community health services to a population of 1.5 million people, which has been undertaking QI at scale since 2014. This paper presents case studies and examples from ELFT to illustrate return on investment from QI at multiple levels: improving outcomes for patients and service users, improving the experience of staff, improving productivity and efficiency, avoiding costs, reducing costs and increasing revenue.

Prenatal folic acid (FA) supplementation prevents neural tube defects. Folate receptor alpha (FRα) is critical for embryonic development, including neural crest (NC) development. Previously we showed that FRα translocates to the nucleus in response to FA, where it acts as a transcription factor. In this study, we examined if FA through interaction with FRα regulates stem cell characteristics of cranial neural crest cells (CNCCs)‐critical for normal development. We hypothesized that FRα upregulates coding genes and simultaneously downregulates non‐coding miRNA which targets coding genes in CNCCs. Quantitative RT‐PCR and chromatin immunoprecipitation showed that FRα upregulates Oct4, Sox2,and Klf4by binding to their cis‐regulator elements‐5′ enhancer/promoters defined by H3K27Ac and p300 occupancy. FA via FRα downregulates miRNAs, miR‐138 and miR‐let‐7, which target Oct4and Trim71(an Oct4 downstream effector), respectively. Co‐immunoprecipitation data suggests that FRα interacts with the Drosha‐DGCR8 complex to affect pre‐miRNA processing. Transfecting anti‐miR‐138 or anti‐miR‐let‐7 into non‐proliferating neural crest cells (NCCs) derived from Splotch(Sp−/−), restored their proliferation potential. In summary, these results suggest a novel pleiotropic role of FRα: (a) direct activation of Oct4, Sox2,and Klf4genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules. StemCells2016;34:2721–2732 Hypothetical model of FRα function in NCCs. In response to FA, FRα translocates to the nucleus where it binds the cis‐regulatory elements of Oct4, Sox2,and Klf4, activating transcription; this in turn activates downstream targets such as Trim71 and downregulates levels of miR‐138 and miR‐let‐7, which target Oct4and Trim71respectively thus removing the inhibitory effects on Oct4and Trim71expression.

Background: Congenital granular cell tumor (CGCT) is a rare benign soft tissue tumor of the new born. It is also called congenital epulis. Case presentation: We report the case of a 3-day-old male neonate who was postnatally noted to have a 2-cm mass over the maxillary alveolar ridge in the midline. The mass was causing feeding difficulties, and hence, decision for surgical excision was taken. The postoperative recovery was uneventful. Conclusion: Congenital granular cell tumor (CGCT) is commonly seen on the gingival margins of the maxilla or mandible. Large tumors may cause polyhydramnios in the antenatal period or feeding and respiratory difficulties in the postnatal period. Diagnosis is usually confirmed by histopathology. Malignant change or recurrence has not been reported following incomplete excision of this mass.

Background: Hamartoma is a benign, tumor-like proliferation of mature tissue that is natural to the organ from which it developed. Oral hamartomas are rare and can occur as an isolated finding or as a part of a syndrome. Case presentation: We report a 4-day-old male neonate who was postnatally noted to have a large 3.5 × 3.5 cm lobulated mass over the tip of the tongue. The mass was causing protrusion of the tongue and feeding difficulties following which surgical excision was planned. The postoperative recovery was uneventful. Conclusion: Although rare, lingual hamartomas should be considered in the differential diagnosis algorithm for congenital tongue lesions. The definitive diagnosis is histopathological with complete resection of the tumor resulting in a favorable prognosis.

Background: Minimally invasive pediatric surgery has gained popularity over open conventional surgery as it offers benefits to both patients and health care practitioners. Creation of pneumoperitoneum is a must for any laparoscopic procedure. Different pediatric surgeons have their individual preferences regarding the technique to create pneumoperitoneum prior to laparoscopy. The aim of this study was to evaluate the preference of technique for the creation of pneumoperitoneum in pediatric laparoscopy among Indian Pediatric Surgeons. The study was designed by communication with members of the Indian Association of Pediatric Surgeons using a predefined questionnaire. 180 pediatric surgeons responded to the survey. The respondents included pediatric surgeons in institutional and private practice. The reasons behind their preference were enumerated and evaluated. Results: Seventy-one percent of pediatric surgeons preferred the primary open technique for the creation of pneumoperitoneum. Seventeen percent exclusively used Veress needle whereas 12% were using both techniques varying from patient to patient. Conclusion: Creation of pneumoperitoneum remains an important safety issue for all pediatric surgeons. Pediatric Surgeons in India prefer using the primary open technique for the creation of pneumoperitoneum for laparoscopic surgery.

Context:A subpopulation of hypothalamic neurons colocalize three neuropeptides, namely kisspeptin, neurokinin B (NKB), and dynorphin, collectively termed KNDy neurons. Animal studies suggest they interact to affect pulsatile GnRH release (KNDy hypothesis); kisspeptin stimulates, NKB modulates, and dynorphin (an opioid) inhibits.Objective:To investigate the KNDy hypothesis in humans, we assessed for the first time the effects of the coadministration of kisspeptin-54, NKB, and an opioid receptor antagonist, naltrexone, on LH pulsatility (surrogate marker for GnRH pulsatility) and gonadotropin release.Design, Setting, and Participants:This was an ethically approved prospective, single-blinded, placebo-controlled study. Healthy male volunteers (n = 5/group) attended our research facility for eight study visits.Intervention and Main Outcome Measure:After 1 hour of baseline blood sampling, participants received a different intervention at each visit: oral 50 mg naltrexone, 8-hour iv infusions of vehicle, 2.56 nmol/kg · h NKB, 0.1 nmol/kg · h kissspeptin-54 (KP) alone and in combination. Frequent blood sampling to measure plasma gonadotropins and sex steroids was conducted and LH pulsatility was determined using blinded deconvolution analysis.Results:All kisspeptin and naltrexone containing groups potently increased LH and LH pulsatility (P< .001 vs vehicle). NKB alone did not affect gonadotropins. NKB+KP had significantly lower increases in gonadotropins compared with kisspeptin alone (P< .01). Naltrexone+KP was the only group to significantly increase LH pulse amplitude (P< .001 vs vehicle).Conclusions:Our results suggest significant interactions between the KNDy neuropeptides on LH pulsatility and gonadotropin release in humans. This has important implications for improving our understanding of GnRH pulse generation in humans.

No relevant conflicts of interest to declare.

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