ß-Catenin transcriptional activity is required for establishment of inner pillar cell identity during cochlear development.

The mammalian cochlea is composed of sensory hair cells as well as multiple different types of non-sensory supporting cells. Pillar cells are one type of supporting cell that form the tunnel of Corti and include two morphologically and functionally distinct subtypes: inner pillar cells (IPCs) and outer pillar cells (OPCs). The processes of specification and differentiation of inner versus outer pillar cells are still unclear. Here, we show that ß-Catenin is required for establishing IPC identity in the mammalian cochlea. To differentiate the transcriptional and adhesion roles of ß-Catenin in establishing IPC identity, we examined two different models of ß-Catenin deletion; one that deletes both transcriptional and structural functions and one which retains cell adhesion function but lacks transcriptional function. Here, we show that cochleae lacking ß-Catenin transcriptional function lost IPCs and displayed extranumerary OPCs, indicating its requirement for establishing IPC identity. Overexpression of ß-Catenin induced proliferation within IPCs but not ectopic IPCs. Single-cell transcriptomes of supporting cells lacking ß-Catenin transcriptional function show a loss of the IPC and gain of OPC signatures. Finally, targeted deletion of ß-Catenin in IPCs also led to the loss of IPC identity, indicating a cell autonomous role of ß-Catenin in establishing IPC identity. As IPCs have the capacity to regenerate sensory hair cells in the postnatal cochlea, our results will aid in future IPC-based hair cell regeneration strategies.

Desorption Electrospray Ionization Cyclic Ion Mobility-Mass Spectrometry Imaging for Traumatic Brain Injury Spatial Metabolomics.

Lipidomics focuses on investigating alterations in a wide variety of lipids that harness important information on metabolic processes and disease pathology. However, the vast structural diversity of lipids and the presence of isobaric and isomeric species creates serious challenges in feature identification, particularly in mass spectrometry imaging experiments that lack front-end separations. Ion mobility has emerged as a potential solution to address some of these challenges and is increasingly being utilized as part of mass spectrometry imaging platforms. Here, we present the results of a pilot mass spectrometry imaging study on rat brains subjected to traumatic brain injury (TBI) to evaluate the depth and quality of the information yielded by desorption electrospray ionization cyclic ion mobility mass spectrometry (DESI cIM MSI). Imaging data were collected with one and six passes through the cIM cell. Increasing the number of passes increased the ion mobility resolving power and the resolution of isobaric lipids, enabling the creation of more specific maps. Interestingly, drift time data enabled the recognition of multiply charged phosphoinositide species in the complex data set generated. These species have not been previously reported in TBI MSI studies and were found to decrease in the hippocampus region following injury. These changes were attributed to increased enzymatic activity after TBI, releasing arachidonic acid that is converted to eicosanoids to control inflammation. A substantial reduction in NAD and alterations in other adenine metabolites were also observed, supporting the hypothesis that energy metabolism in the brain is severely disrupted in TBI.

Identifying at risk populations amongst breast cancer survivors and their common symptoms and concerns.

PURPOSE: The survival rate amongst breast cancer survivors (BCS) have been increasing, with a 5-year survival rate of almost 90%. These women face many quality of life (QOL) issues either due to either cancer itself or the complex treatment regimen. Our retrospective analysis aims to identify at risk populations among the BCS and their most common concerns. METHODS: This is a single-institution, retrospective, descriptive analysis of patients who were seen at our Breast Cancer Survivorship Program from October 2016 to May 2021. Patients completed a comprehensive survey which assessed self-reported symptoms, their concerns and degree of worry and recovery to baseline. The descriptive analysis on the patient characteristics included age, cancer stage and treatment type. The bivariate analysis included the relationship between the patient characteristics and their outcomes. Analysis of group differences was completed with Chi-square test. When the expected frequencies were five or less, Fisher exact test was used. Logistic regression models were developed to identify significant predictors for outcomes. RESULTS: 902 patients (age 26-94; median 64) were evaluated. Majority of women had stage 1 breast cancer. The most common self-reported concerns affecting the patients were fatigue (34%), insomnia (33%), hot flashes (26%), night sweats (23%), pain (22%), trouble concentrating (19%), and neuropathy (21%). Though 13% of BCS felt isolated at least 50% of their time, the majority of patients (91%) reported having a positive outlook and felt that they have a sense of purpose (89%). Younger patients were more likely to worry about their cancer more than 50% of the time (p < 0.0001). Patients that were less likely to return back to at least 50% of their pre-treatment baseline were younger (age ≤ 45) (p = 0.0280), had higher stage breast cancer (Stage 2-4) (p = 0.0061), and had chemotherapy either alone or as part of their multi-modality treatment (p < 0.0001). CONCLUSION: According to our study, younger patients, those with higher stage breast cancer and survivors who had chemotherapy may experience significant QOL issues. Fortunately, majority of BCS report a positive and optimistic outlook post treatment. Identifying common concerns after treatments and vulnerable populations are especially important to deliver quality care and to optimize interventions. IMPLICATIONS FOR CANCER SURVIVORS: Our study identified the most common self-reported concerns affecting BCS. In addition, our results suggest that younger patients, patients with higher stage breast cancer and survivors who had chemotherapy were more likely to have QOL issues. Despite this, our study showed, the majority of BCS reported positive outlooks and emotions.

Candidate pathways for retina to scleral signaling in refractive eye growth.

The global prevalence of myopia, or nearsightedness, has increased at an alarming rate over the last few decades. An eye is myopic if incoming light focuses prior to reaching the retinal photoreceptors, which indicates a mismatch in its shape and optical power. This mismatch commonly results from excessive axial elongation. Important drivers of the myopia epidemic include environmental factors, genetic factors, and their interactions, e.g., genetic factors influencing the effects of environmental factors. One factor often hypothesized to be a driver of the myopia epidemic is environmental light, which has changed drastically and rapidly on a global scale. In support of this, it is well established that eye size is regulated by a homeostatic process that incorporates visual cues (emmetropization). This process allows the eye to detect and minimize refractive errors quite accurately and locally over time by modulating the rate of elongation of the eye via remodeling its outermost coat, the sclera. Critically, emmetropization is not dependent on post-retinal processing. Thus, visual cues appear to influence axial elongation through a retina-to-sclera, or retinoscleral, signaling cascade, capable of transmitting information from the innermost layer of the eye to the outermost layer. Despite significant global research interest, the specifics of retinoscleral signaling pathways remain elusive. While a few pharmacological treatments have proven to be effective in slowing axial elongation (most notably topical atropine), the mechanisms behind these treatments are still not fully understood. Additionally, several retinal neuromodulators, neurotransmitters, and other small molecules have been found to influence axial length and/or refractive error or be influenced by myopigenic cues, yet little progress has been made explaining how the signal that originates in the retina crosses the highly vascular choroid to affect the sclera. Here, we compile and synthesize the evidence surrounding three of the major candidate pathways receiving significant research attention - dopamine, retinoic acid, and adenosine. All three candidates have both correlational and causal evidence backing their involvement in axial elongation and have been implicated by multiple independent research groups across diverse species. Two hypothesized mechanisms are presented for how a retina-originating signal crosses the choroid - via 1) all-trans retinoic acid or 2) choroidal blood flow influencing scleral oxygenation. Evidence of crosstalk between the pathways is discussed in the context of these two mechanisms.

Pre-clinical evaluation of Minnelide as a therapy for acute myeloid leukemia.

BACKGROUND: There is an urgent need for novel and effective treatment options for acute myeloid leukemia (AML). Triptolide, a diterpenoid tri-epoxide compound isolated from the herb Tripterygium wilfordii and its water-soluble pro-drug-Minnelide have shown promising anti-cancer activity. A recent clinical trial for patients with solid tumors confirmed the safety and efficacy at biologically equivalent doses of 0.2 mg/kg/day and lower. METHODS: Cell viability of multiple AML cell lines as well as patient apheresis samples were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) based assay. Apoptosis was evaluated by estimating the amount of cleaved caspase. AML cell line (THP1-Luc) was implanted in immunocompromised mice and treated with indicated doses of Minnelide. Leukemic burden before and after treatment was evaluated by imaging in an In Vivo Imaging System (IVIS). RESULTS: In the current study, we show that Minnelide, at doses below maximum tolerated dose (MTD) demonstrates leukemic clearance of both primary AML blasts and luciferase expressing THP-1 cells in mice. In vitro, multiple primary AML apheresis samples and AML cell lines (THP-1, KG1, Kasumi-1, HL-60) were sensitive to triptolide mediated cell death and apoptosis in low doses. Treatment with triptolide led to a significant decrease in the colony forming ability of AML cell lines as well as in the expression of stem cell markers. Additionally, it resulted in the cell cycle arrest in the G1/S phase with significant downregulation of c-Myc, a major transcriptional regulator mediating cancer cell growth and stemness. CONCLUSION: Our results suggest that Minnelide, with confirmed safety and activity in the clinic, exerts a potent anti-leukemic effect in multiple models of AML at doses easily achievable in patients.

Correction to: Pre-clinical evaluation of Minnelide as a therapy for acute myeloid leukemia.

Following publication of the original article [1], the authors found an error in Figure 3. The middle panel of Figure 3a was inadvertently duplicated.

Emerging Landscape of Antibiotic Resistance and Use of Endoscopic Injection in Vesicoureteral Reflux.

Vesicoureteral reflux (VUR) in children is often treated with antimicrobials for prolonged durations, which often leads to antimicrobial resistance. In this context, this review article discusses the use of endoscopic injection in VUR as a safe and efficacious option for these children. The literature pertaining to VUR- its clinical manifestation and management, antibiotic resistance- with special reference to management of VUR, and endoscopic dextranomer/hyaluronic acid gel injection for management of VUR was reviewed by identifying key words in a PubMed search. Vesicoureteral reflux is managed using antibiotic prophylaxis, urotherapy, or surgical correction (open, endoscopic injection therapy, or laparoscopic). Continuous antibiotic prophylaxis for urinary tract infections in VUR can lead to antibiotic resistance. Urotherapy cures about 75% of cases with dysfunctional voiding and the rest have to be managed at specialized centers. While open surgery provides relief of VUR and related complications in majority, it requires hospitalization. Endoscopic injection of dextranomer/hyaluronic acid gel into the submucosa of bladder or ureter near ureteral orifice increases the tissue bulk and creates a valve function. Various studies show the efficacy and safety of endoscopic injection of dextranomer/hyaluronic acid gel in VUR. The use of endoscopic injection being a non-invasive modality, can be performed in children with VUR in the outpatient department, precluding hospitalization. In view of the threat of developing antimicrobial resistance and also realising the need for definitive treatment of VUR, endoscopic injection is an efficacious and safe option in primary VUR.

New-Onset Occipital Lobe Epilepsy in an Elderly Patient With Visual Hallucinations and Hemianopia.

Occipital lobe epilepsies (OLEs) are a subset of epileptic disorders manifesting predominantly with visual and oculomotor abnormalities that are often misdiagnosed due to similarities with migraines with visual aura and other central nervous system (CNS) pathologies. This case study describes an 88-year-old male with a three-week history of intermittent kaleidoscopic visual phenomena, accompanied by blurring of vision and altered level of consciousness. Neurological examination revealed right homonymous hemianopsia and focal neurological deficits, including forced right gaze preference and nystagmus. Diagnostic modalities, MRI and MRA, ruled out ischemic stroke but indicated mild to moderate cerebral atrophy and chronic microvascular ischemic changes. The patient exhibited a seizure episode characterized by right-sided gaze preference and altered consciousness. Postictally, transient right homonymous hemianopsia was observed, consistent with Todd's phenomenon. Treatment with intravenous levetiracetam and lorazepam led to a reduction in seizure frequency. This case highlights the importance of comprehensive evaluation in distinguishing OLEs from other conditions with similar visual presentations like migraine with aura or occipital lobe stroke being more predominant.

Food Stuck in the Throat in a Newly Diagnosed Diabetes Mellitus Patient: An Atypical Presentation of Wallenberg's Syndrome.

Wallenberg's syndrome, also known as posterior inferior cerebellar artery syndrome (lateral medullary syndrome), is known to be a common cause of posterior ischemic stroke syndromes in men in their 60s and may present with varied symptoms devoid of focal neurological signs making it easily missed as a differential of posterior ischemic strokes. It involves a stroke in the vertebral or posterior inferior cerebellar artery of the brainstem. In this case report, we critically examine the case of a 66-year-old man with newly diagnosed diabetes whose main presentation was dysphagia and unsteady gait. There was no motor or sensory examination finding in our patient, and the initial computed tomography of the brain was negative for any intracranial pathology leading to very low suspicion of stroke. However, given a high index of suspicion and a thorough oropharyngeal examination ruling out structural abnormality, magnetic resonance imaging of the brain revealed features suggestive of Wallenberg's syndrome. This case emphasizes careful consideration of posterior stroke syndrome when evaluating patients presenting with dysphagia without typical motor/sensory symptoms of cerebrovascular accident and the requirement of further imaging to support the diagnosis.

Physiological and regenerative functions of sterile-α motif protein-14 in hematopoiesis.

Sterile α-motif domain-14 (Samd14) protein expression increases the regenerative capacity of the erythroid system. Samd14 is transcriptionally upregulated and promotes cell signaling via the receptor tyrosine kinase Kit in a critical window of acute erythroid regeneration. We generated a hematopoietic-specific conditional Samd14 knockout mouse model (Samd14-CKO) to study the role of Samd14 in hematopoiesis. The Samd14-CKO mouse was viable and exhibited no steady-state hematopoietic phenotype. Samd14-CKO mice were hypersensitive to 5-fluorouracil, resulting in more severe anemia during recovery and impaired erythroid progenitor colony formation. Ex vivo, Samd14-CKO hematopoietic progenitors were defective in their ability to form mast cells. Samd14-CKO mast cells exhibited altered Kit/stem cell factor (SCF), IL-3/IL-3R signaling, and less granularity than Samd14-FL/FL cells. Our findings indicate that Samd14 promotes both erythroid and mast cell functions. The Samd14-CKO mouse phenotype exhibits striking similarities to the KitW/W-v mice, which carry Kit mutations resulting in reduced tyrosine kinase-dependent signaling, causing mast cell and erythroid abnormalities. The Samd14-CKO mouse model is a new tool for studying hematologic pathologies involving Kit signaling.

A Comprehensive Systematic Review of the Latest Management Strategies for Hepatorenal Syndrome: A Complicated Syndrome to Tackle.

Hepatorenal syndrome (HRS), defined by the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduced renal blood flow and glomerular filtration rate. It is diagnosed with reduced kidney function confirming the absence of intrinsic kidney disease, such as hematuria or proteinuria. HRS is potentially reversible with liver transplantation or vasoconstrictor drugs. The condition carries a poor prognosis with high mortality rates, particularly in patients with advanced cirrhosis. The latest management for HRS involves a combination of pharmacological and non-pharmacological interventions, aiming to improve renal function and reduce the risk of mortality. Pharmacological treatments include vasoconstrictors, such as terlipressin and midodrine, and albumin infusion, which have been shown to improve renal function and reduce mortality in HRS patients. Non-pharmacological interventions, including invasive procedures such as transjugular intrahepatic portosystemic shunt (TIPS), plasma exchange, liver transplantation, and renal replacement therapy, may also be considered. Though TIPS has been shown to be effective in improving renal function in HRS patients, liver transplantation remains at the top of the consideration for the treatment of end-stage liver disease and HRS. Recent studies have placed importance on early recognition and prompt intervention in HRS patients, as delaying treatment can result in poorer outcomes. Although there are numerous reviews that summarize various aspects of HRS, the recent advancements in the management and pathophysiology of HRS are still insufficient. Therefore, in this review, we summarized a brief pathophysiology and highlighted recent advancements in the management of HRS with a quick review of the latest articles.

Annular pancreas: Beneath the intestinal obstruction-A case report.

Annular pancreas is an uncommon congenital anomaly which is a rare cause of congenital duodenal obstruction. It is normally identified during the neonatal period, but may also be identified in adolescence or adulthood. This diagnosis is often overlooked in adult patients who present with symptoms suggestive of duodenal obstruction. We present a case of AP detected in a 23-year-old man, with complaints of continuous vomiting and abdominal discomfort over the last 6 months. An upper gastrointestinal study revealed a constricted second part of the duodenum. A computed tomography scan revealed a complete ring of pancreatic tissue around the second part of the duodenum. Diagnostic and therapeutic surgery decompresses the external obstruction. The patient had an early post-operative activation. No specific guidelines and protocols exist about the management of such cases. Given the rarity of this congenital anomaly, presenting with chronic partial duodenal obstruction, and its successful surgical treatment, have prompted us to report the case along with a brief review of literature about the subject.

Pneumonia or Kaposi Sarcoma: Beneath the Dyspnea With Non-compliance of HIV.

Human herpesvirus 8 (HHV-8) or Kaposi sarcoma herpesvirus is the cause of Kaposi sarcoma (KS), the most prevalent cancer related to acquired immune deficiency syndrome. About 90% of the time, KS is accompanied by cutaneous lesions; however, systemic illness can develop without cutaneous involvement. Today's highly active antiretroviral therapy (HAART) era has seen a decrease in the prevalence of KS. In immunocompromised individuals, it may be challenging to differentiate between pneumonia and the clinical characteristics of pulmonary KS, which might make diagnosis more challenging. HAART is the first-line therapy for KS, and its usage has reduced the incidence of KS. Depending on how severe the illness is, systemic chemotherapy could be helpful. We report the case of a young man who presented with pulmonary symptoms in the presence of a pharyngeal mass and was later found to have bilateral pulmonary metastasis. Interestingly, this diagnosis was made in the absence of classic cutaneous lesions. The patient was counseled for quality of life with medication and intervention compliance, and a consultation with an oncologist was set up.

Secretory Carcinoma of the Breast Mimicking Invasive Ductal Carcinoma: A Case Report.

BACKGROUND Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation. CASE REPORT A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment. CONCLUSIONS Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.

A Case Report on BRASH (Bradycardia, Renal Failure, Atrioventricular Blockade, Shock, and Hyperkalaemia) Syndrome: A Challenging Diagnosis.

A relatively new yet critical phenomenon of bradycardia, renal failure, atrioventricular (AV) blockade, shock, and hyperkalemia (BRASH) syndrome is hypothesized to happen in patients who take atrioventricular nodal blocking (AVNB) agents and have underlying renal insufficiency. In our case, a 67-year-old female with an extensive medical history presented to the emergency room with chief complaints of decreased appetite, nausea, vomiting, fatigue, and left-sided atypical chest pain for the past two weeks. The patient was taking losartan potassium 50 mg daily in addition to carvedilol 6.25 mg twice daily for her hypertension (HTN) and heart failure with reduced ejection fraction (HFrEF) with the addition of bumetanide 0.5 mg, which was added three weeks prior. On presentation, the patient had sinus bradycardia and hypotension along with the laboratory finding of acute kidney injury (AKI) in the setting of chronic kidney disease (CKD) and hyperkalemia. Cardiology and nephrology were consulted emergently; her clinical scenario raised suspicion of the BRASH syndrome. The patient was admitted to the intensive care unit (ICU), and all antihypertensive medications, including beta-blockers, were stopped. Intravenous (IV) fluid resuscitation and medical management of hyperkalemia were initiated, along with BiPAP for respiratory distress. She responded significantly, and her vitals remained stable. She was successfully discharged home with a cardiology and nephrology follow-up. We highlight the case to emphasize the consideration of BRASH in a patient on multiple cardiac medications who presented with deranged electrolytes and organ failure, and decompensated heart failure (HF) should not be fixed on as the principal diagnosis.

Regulation of Schwann Cell and DRG Neurite Behaviors within Decellularized Peripheral Nerve Matrix.

Decellularized nerve hydrogels (dNHs) containing bioactive molecules are promising biomaterials for peripheral nerve injury (PNI) treatment and have been extensively applied in clinical and preclinical practice. However, most previous research projects studied their influences on nerve-related cellular behaviors in two dimensions (2D) without taking hydrogel biomechanics into consideration. The molecular mechanisms underlying the beneficial microenvironment provided by dNHs also remain unclear. In this study, dNHs from rat sciatic nerves were prepared, and their effects on Schwann cell (SC) and dorsal root ganglion (DRG) neurite behaviors were evaluated and compared to commercial rat tail type I collagen (Col) hydrogels in three-dimensional (3D) environments. We found that dNHs could promote SC proliferation and neurite outgrowth, and both the hydrogel mechanics and components contributed to the dNH functionalization. Through proteomics analysis, we found that laminin (LAM) and type V collagen (COLV) exclusively and abundantly existed in dNHs. By adding exogenous LAM and COLV into Col hydrogels, we demonstrated that they regulated SC gene expression and that LAM could promote SC spreading and neurite outgrowth, while COLV improved SC proliferation. Lastly, dNHs were fabricated into paper-like, aligned nerve scaffolds through unidirectional freezing to expand the dNH applications in PNI treatment.

Biliary cystadenoma: Case report with MRI findings and surgical confirmation.

Biliary cystadenoma is a very uncommon benign cystic neoplasm involving the liver and the biliary tract. Most common presentations include right upper quadrant pain, nausea, vomiting, obstructive jaundice, and enlarging liver size. It can mimic many more commonly occurring diseases such as hepatic cyst, hepatic abscess, hydatid disease of the liver, and hepatic tuberculosis. Hence it becomes very challenging for physicians to correctly diagnose it due to its rarity and similarity with other conditions. Furthermore, very few pieces of literature guide physicians in correctly identifying the disease. Based on his physical examination and detailed investigation, we present a case report of a 72-year-old female diagnosed with biliary cystadenoma. We hope that this case report will significantly add to the existing literature on this subject.

Gorham-Stout disease, a diagnosis of exclusion.

Gorham-Stout disease (GSD) also known as vanishing bone disease is an idiopathic and rare condition characterized by gross and progressive bone loss along with excessive growth of vascular and lymphatic tissue. Very little is known about the pathogenesis of GSD, which makes the diagnosis challenging and often diagnosed by elimination. We report a case of GSD in a 41-year-old male patient. He presented with bone pain and initial imaging showed widespread osteolytic lesions in the cervical and mid thoracic spine, ribs, sternum, clavicles, scapula, and humerus. Two percutaneous bone biopsies were performed, followed by an open spine biopsy of the lumber 2 spinous process for histological examination. Unfortunately, no diagnosis was reached. Although, he was treated symptomatically, he kept enduring pain and presented again after 7 months. His laboratory values were out of the normal range which prompted thorough investigations. New imaging and bone biopsy revealed multiple osteolytic lesions and vascular lesion with cavernous morphology respectively. GSD was diagnosed after ruling out a neoplastic process and confirming the cavernous morphology with immunohistochemical stain. He was treated symptomatically with immunomodulators, bisphosphonates, and supplements. Patient was counseled to see the specialist regularly. This case will help to increase familiarity and shed insights in the diagnosis of GSD.

Septo-optic dysplasia in an infant.

Septo-optic dysplasia (SOD) is a rare congenital disorder occurring in only 1 in 10,000 live births. Initially it was described in 1941 by Reeves and further discussed by the French-Swiss neurologist de Morsier (1956) as the disease further addressed his name. SOD is a combination of triads of hypoplasia of the optic nerve, agenesis of midline brain structures, and hypoplasia of the hypothalamic-pituitary axis. The pathophysiology of this rare congenital anomaly is yet to be understood, with some hypotheses in order to establish the diagnosis. The management modality depends on the presentation of the disease and requires a multidisciplinary approach. While most SOD patients present with visual, neurological, or endocrine abnormalities, in our case the patient was diagnosed incidentally while following up after an episode of acute respiratory distress syndrome and sepsis. We aim to highlight the aspects of clinical presentation in a patient with SOD and the importance of a multimodality follow-up approach.

Genesis of fecal floatation is causally linked to gut microbial colonization in mice.

The origin of fecal floatation phenomenon remains poorly understood. Following our serendipitous discovery of differences in buoyancy of feces from germ-free and conventional mice, we characterized microbial and physical properties of feces from germ-free and gut-colonized (conventional and conventionalized) mice. The gut-colonization associated differences were assessed in feces using DNA, bacterial-PCR, scanning electron microscopy, FACS, thermogravimetry and pycnometry. Based on the differences in buoyancy of feces, we developed levô in fimo test (LIFT) to distinguish sinking feces (sinkers) of germ-free mice from floating feces (floaters) of gut-colonized mice. By simultaneous tracking of microbiota densities and gut colonization kinetics in fecal transplanted mice, we provide first direct evidence of causal relationship between gut microbial colonization and fecal floatation. Rare discordance in LIFT and microbiota density indicated that enrichment of gasogenic gut colonizers may be necessary for fecal floatation. Finally, fecal metagenomics analysis of 'floaters' from conventional and syngeneic fecal transplanted mice identified colonization of > 10 gasogenic bacterial species including highly prevalent B. ovatus, an anaerobic commensal bacteria linked with flatulence and intestinal bowel diseases. The findings reported here will improve our understanding of food microbial biotransformation and gut microbial regulators of fecal floatation in human health and disease.