Neglected Superior Dislocation of the Shoulder Joint: A Case Report.

The anterior subtype of shoulder dislocations constitutes the vast majority that either reduces instantly or is reduced at the point of care with no serious complexities. The posterior ones are infrequent and inferior and superior dislocations are even more rare. Rupture of the deltoid is considered to be linked with superior dislocation; regardless, very few articles are available pertaining to the mechanism of onset and the management of a superior shoulder dislocation. In the line of traumatic shoulder dislocations, we present a one-year-old neglected case of a 23-year-old male who sustained an open injury over the right outstretched upper arm, abducted at an angle of approximately 45° due to a fall from a height of approximately 18 feet. This unique report outlines the various surgical modalities available, given the patient's late presentation due to neglect.

The Neural Progenitor Cell-Associated Transcription Factor FoxG1 Regulates Cardiac Epicardial Cell Proliferation.

The epicardium is a layer of mesothelial cells that covers the surface of the heart. During development, epicardial cells undergo epithelial-to-mesenchymal transition (EMT) to form multipotent precursors that migrate into the heart and contribute to the coronary vasculature by differentiating into adventitial fibroblasts, smooth muscle cells, and endothelial cells. Epicardial cells also provide paracrine signals to cardiac myocytes that are required for appropriate heart growth. In adult hearts, a similar process of epicardial cell EMT, migration, and differentiation occurs after myocardial infarction (MI, heart attack). Pathological cardiac hypertrophy is associated with fibrosis, negative remodeling, and reduced cardiac function. In contrast, aerobic exercises such as swimming and running promote physiological (i.e., beneficial) hypertrophy, which is associated with angiogenesis and improved cardiac function. As epicardial cell function(s) during physiological hypertrophy are poorly understood, we analyzed and compared the native epicardial cells isolated directly from the hearts of running-exercised mice and age-matched, nonrunning littermates. To obtain epicardial cells, we enzymatically digested the surfaces of whole hearts and performed magnetic-activated cell sorting (MACS) with antibodies against CD104 (integrin ß4). By cDNA microarray assays, we identified genes with increased transcription in epicardial cells after running exercise; these included FoxG1, a transcription factor that controls neural progenitor cell proliferation during brain development and Snord116, a small noncoding RNA that coordinates expression of genes with epigenetic, circadian, and metabolic functions. In cultured epicardial cells, shRNA-mediated FoxG1 knockdown significantly decreased cell proliferation, as well as Snord116 expression. Our results demonstrate that FoxG1 regulates epicardial proliferation, and suggest it may affect cardiac remodeling.

Malunion of a Clavicle Fracture in a Young Adult: A Case Report and Surgical Intervention.

This case study examines the medical complexity of managing a neglected clavicle in a young patient, resulting in a complicated interstitial non-union. Despite initial therapeutic efforts, the fracture was not treated, resulting in significant pain as well as functional and aesthetic disabilities. This case outlines accurate clinical presentation and diagnostic methods. In addition, malunion clavicle fractures require multifaceted therapeutic approaches including surgical interventions, rehabilitation programs, and psychological support. Through comprehensive research and long-term follow-up, this report reveals the complexity of traumatic fractures, highlighting the importance of early recognition and intervention. To address the issue effectively, it is essential to follow a multidisciplinary approach that includes physical assessment, pharmacotherapy, and physiotherapy. This case report aims to highlight the critical role of comprehensive individual care in improving the patient's condition and emphasizes the importance of vigilant healthcare practices.

Lacertus Fibrosus Syndrome: A Case Report.

Lacertus fibrosus syndrome is described as compression of the median nerve, which takes place beneath a layer of ligamentous tissue (lacertus fibrosus, also known as bicipital aponeurosis) slightly beyond the elbow joint. Both sexes can develop lacertus fibrosus syndrome, most often after the age of 35. The possible risk factors are repetition of movements, overwork, and manual work while the forearm is pronated. Lacertus fibrosus syndrome presents a distinct diagnostic challenge because it is a somewhat unknown and non-documented disease. Its symptoms are often mistaken for those of carpal tunnel syndrome, which complicates the differential diagnosis and management of the patient. All patients who report tingling, numbness, loss of strength, muscle loss, manual endurance, or dexterity should be investigated and tested for both carpal tunnel syndrome and lacertus syndrome. Here, a case of a 43-year-old woman is discussed, who presented with chief complaints of pain and tingling sensation in the left upper limb, which was associated with loss of thumb pinch grip. The pain was aggravated with elbow extension and relieved with rest. The patient underwent left elbow median nerve decompression and was discharged in steady condition. This case report highlights the accurate clinical presentation and surgical intervention for the syndrome, for which the outcome turned out to be satisfying.

Idiopathic Capital Femoral Chondrolysis: A Case Report.

Idiopathic capital femoral chondrolysis is a rare condition most commonly seen in African-American pre-adolescent females. The primary symptoms are hip stiffness and pain, which are accompanied by limping. Physical examinations typically reveal an external rotation contracture, flexion contracture, and abduction contracture. There is also immobility at the hip secondary to muscle spasms. Here, we present and discuss the follow-up case of a 10-year-old female patient who was diagnosed with idiopathic chondrolysis of capital femoral epiphysis, right side, and underwent right hip arthroscopic evaluation and lavage. At follow-up two months after the right hip arthroscopic evaluation, she presented with painless limping on the right side. The patient underwent soft tissue release right hip under general anaesthesia and was discharged in stable condition.

SetD7 (Set7/9) is a novel target of PPARγ that promotes the adaptive pancreatic ß-cell glycemic response.

Loss of functional pancreatic ß-cell mass leads to type 2 diabetes (T2D), attributable to modified ß-cell-dependent adaptive gene expression patterns. SetD7 is a histone methyltransferase enriched in pancreatic islets that mono- and dimethylates histone-3-lysine-4 (H3K4), promoting euchromatin modifications, and also maintains the regulation of key ß-cell function and survival genes. However, the transcriptional regulation of this important epigenetic modifier is unresolved. Here we identified the nuclear hormone receptor peroxisome proliferator-activated receptor-gamma (PPARγ) as a major transcriptional regulator of SetD7 and provide evidence for direct binding and functionality of PPARγ in the SetD7 promoter region. Furthermore, constitutive shRNA-mediated PPARγ knockdown in INS-1 ß-cells or pancreas-specific PPARγ deletion in mice led to downregulation of SetD7 expression as well as its nuclear enrichment. The relevance of the SetD7-PPARγ interaction in ß-cell adaptation was tested in normoglycemic 60% partial pancreatectomy (Px) and hyperglycemic 90% Px rat models. Whereas a synergistic increase in islet PPARγ and SetD7 expression was observed upon glycemic adaptation post-60% Px, in hyperglycemic 90% Px rats, islet PPARγ, and PPARγ targets SetD7 and Pdx1 were downregulated. PPARγ agonist pioglitazone treatment in 90% Px rats partially restored glucose homeostasis and ß-cell mass and enhanced expression of SetD7 and Pdx1. Collectively, these data provide evidence that the SetD7-PPARγ interaction serves as an important element of the adaptive ß-cell response.

Rash Decisions in Neurology: A Case Report of Brachioradial Pruritus Secondary to Cervical Intramedullary Lesion.

Brachioradial pruritus (BRP) is an enigmatic condition often encountered by dermatologists and passed off as a benign itch. It is an "idiopathic" pruritus, presenting as severe itching on the radial aspect of the elbow. The physical examination may be unremarkable except for mild pruritic lesions. Hence, the patient is treated with local applications of sunscreens, anti-inflammatory agents, anti-histamines and steroids, most of which prove to be ineffective. Dermatomal localization of localization of pruritis has suggested cervical myeloradiculopathy as a novel aetiology and this has been elucidated in recent studies. Here we report a young man, who presented with brachioradial pruritus and was diagnosed to have a C6-7 intramedullary cervical cord lesion.

Deep Cerebral Venous Thrombosis-A Clinicoradiological Study.

Stroke is a common neurological emergency. Almost 80% of strokes are due to arterial occlusion. Venous thrombosis comprises less than 1-2% of all strokes. Involvement of the deep cerebral venous system is still rare and accounts for about 10.9% of all cerebral venous thromboses (CVT). CVT diagnosis is often delayed or missed, because of its variable clinical manifestations. We retrospectively (2015-18) and prospectively (2018-20) reviewed all the cases of CVT in a tertiary care center in south India. Out of a total of 52 CVT cases, 12 were due to the involvement of deep cerebral venous system. Their clinical presentation, imaging characteristics, and outcomes were assessed. The most frequent presentation was headache followed by seizures. Hyperhomocysteinemia was the most common risk factor noted. Imaging characteristics were variable, and a high index of suspicion was required for early diagnosis. All patients had favorable outcome in our study, and except one, all were treated conservatively.

Transcranial Doppler for Monitoring and Evaluation of Idiopathic Intracranial Hypertension.

Background Idiopathic intracranial hypertension (IIH) is a disorder of unknown origin, characterized by features of raised intracranial pressure (ICP). Existing literature is inconclusive about the role of transcranial Doppler (TCD) in the management of IIH. Objective To study the TCD changes in IIH patients, pre- and post-cerebrospinal fluid (CSF) drainage. Materials and Methods This was a prospective study, conducted between July 2017 and December 2019, in a tertiary care referral center in South India. Sixteen consecutive patients, suspected to have IIH, underwent magnetic resonance imaging ofthe brain, a baseline TCD, and lumbar puncture with CSF drainage and pressure monitoring. Post-CSF drainage, TCD was repeated and mean flow velocities, peak systolic velocities, end-diastolic velocities, and pulsatility index (PI), in the middle cerebral artery (MCA), vertebral artery, and basilar artery (BA) were noted. Thirteen patients had elevated CSF pressure, and fulfilled the diagnostic criteria for IIH. These patients were included in the final analysis and pre- and post-CSF drainage TCD blood flow velocities and PI were compared. Results The mean age of study participants was 29.92 ± 6.92 years. There was a significant reduction in the cerebral flow velocities in bilateral MCA, after CSF drainage and normalization of ICP. Flow velocities in posterior circulation and PI in MCA, PCA, and BA showed an insignificant reduction. Two patients, who did not show any reduction in flow velocities after CSF drainage, developed optic atrophy on follow-up. Conclusion TCD-derived systolic blood flow velocities can be used in the management and follow-up of patients with IIH.

Effects of Pioglitazone on Glucose-Dependent Insulinotropic Polypeptide-Mediated Insulin Secretion and Adipocyte Receptor Expression in Patients With Type 2 Diabetes.

Incretin hormone dysregulation contributes to reduced insulin secretion and hyperglycemia in patients with type 2 diabetes mellitus (T2DM). Resistance to glucose-dependent insulinotropic polypeptide (GIP) action may occur through desensitization or downregulation of ß-cell GIP receptors (GIP-R). Studies in rodents and cell lines show GIP-R expression can be regulated through peroxisome proliferator-activated receptor γ (PPARγ) response elements (PPREs). Whether this occurs in humans is unknown. To test this, we conducted a randomized, double-blind, placebo-controlled trial of pioglitazone therapy on GIP-mediated insulin secretion and adipocyte GIP-R expression in subjects with well-controlled T2DM. Insulin sensitivity improved, but the insulinotropic effect of infused GIP was unchanged following 12 weeks of pioglitazone treatment. In parallel, we observed increased GIP-R mRNA expression in subcutaneous abdominal adipocytes from subjects treated with pioglitazone. Treatment of cultured human adipocytes with troglitazone increased PPARγ binding to GIP-R PPREs. These results show PPARγ agonists regulate GIP-R expression through PPREs in human adipocytes, but suggest this mechanism is not important for regulation of the insulinotropic effect of GIP in subjects with T2DM. Because GIP has antilipolytic and lipogenic effects in adipocytes, the increased GIP-R expression may mediate accretion of fat in patients with T2DM treated with PPARγ agonists.

Wake-Up Sleepyhead: Unilateral Diencephalic Stroke Presenting with Excessive Sleepiness.

Altered sleep architecture and stroke share a reciprocal relationship. More than half of the stroke patients display sleep abnormalities including hypersomnia, insomnia, parasomnia, periodic limb movements, or sleep-disordered breathing. Conversely, one of the major causes of severe organic hypersomnia is acute brainstem strokes, involving thalamic infarctions, which may be reversible over 6-12 months. Here, we report a patient with increased lethargy and drowsiness who was diagnosed to have a right thalamic and hypothalamic ischemic stroke.

ß-Cell mass restoration by α7 nicotinic acetylcholine receptor activation.

Although it is well-established how nutrients, growth factors, and hormones impact functional ß-cell mass (BCM), the influence of the central nervous system in this regard, and especially in the context of islet immune modulation, has been understudied. Here we investigated the expression and activity of pancreatic islet α7 nicotinic acetylcholine receptor (α7nAChR) in islet anti-inflammatory and prosurvival signaling. Systemic administration of α7nAChR agonists in mice improved glucose tolerance and curtailed streptozotocin-induced hyperglycemia by retaining BCM, in part through maintaining Pdx1 and MafA expression and reducing apoptosis. α7nAChR activation of mouse islets ex vivo led to reduced inflammatory drive through a JAK2-STAT3 pathway that couples with CREB/Irs2/Akt survival signaling. Because the vagus nerve conveys anti-inflammatory signals to immune cells of the spleen and other nonneural tissues in the viscera by activating α7nAChR agonists, our study suggests a novel role for ß-cell α7nAChR that functions to maintain ß-cell survival and mass homeostasis through modulating islet cytokine and phosphatidylinositol 3-kinase-dependent signaling pathways. Exploiting these pathways may have therapeutic potential for the treatment of autoimmune diabetes.

Temporal characterization of ß cell-adaptive and -maladaptive mechanisms during chronic high-fat feeding in C57BL/6NTac mice.

The onset of type 2 diabetes is characterized by transition from successful to failed insulin secretory compensation to obesity-related insulin resistance and dysmetabolism. Energy-rich diets in rodents are commonly studied models of compensatory increases in both insulin secretion and ß cell mass. However, the mechanisms of these adaptive responses are incompletely understood, and it is also unclear why these responses eventually fail. We measured the temporal trends of glucose homeostasis, insulin secretion, ß cell morphometry, and islet gene expression in C57BL/6NTac mice fed a 60% high-fat diet (HFD) or control diet for up to 16 weeks. A 2-fold increased hyperinsulinemia was maintained for the first 4 weeks of HFD feeding and then further increased through 16 weeks. ß cell mass increased progressively starting at 4 weeks, principally through nonproliferative growth. Insulin sensitivity was not significantly perturbed until 11 weeks of HFD feeding. Over the first 8 weeks, we observed two distinct waves of increased expression of ß cell functional and prodifferentiation genes. This was followed by activation of the unfolded protein response at 8 weeks and overt ß cell endoplasmic reticulum stress at 12-16 weeks. In summary, ß cell adaptation to an HFD in C57BL/6NTac mice entails early insulin hypersecretion and a robust growth phase along with hyperexpression of related genes that begin well before the onset of observed insulin resistance. However, continued HFD exposure results in cessation of gene hyperexpression, ß cell functional failure, and endoplasmic reticulum stress. These data point to a complex but not sustainable integration of ß cell-adaptive responses to nutrient overabundance, obesity development, and insulin resistance.

Effects of glucose and insulin on secretion of amyloid-ß by human adipose tissue cells.

OBJECTIVE: Obesity and type 2 diabetes mellitus are risk factors for developing Alzheimer disease. Overlapping patterns of metabolic dysfunction may be common molecular links between these complex diseases. Amyloid-ß (Aß) precursor protein and associated ß- and γ-secretases are expressed in adipose tissue. Aß precursor protein is up-regulated with obesity and correlated to insulin resistance. Aß may be secreted by adipose tissue, its production may be regulated through metabolic pathways, and Aß may exert effects on adipose tissue insulin receptor signaling. METHODS: Human stromal-vascular cells and differentiated adipocytes were cultured with different combinations of glucose and insulin and then assayed for Aß in conditioned media. Aß was measured in vivo using adipose tissue microdialysis. RESULTS: Aß secretion was increased by glucose and insulin in vitro. Adipose tissue microdialysates contained Aß. Adipocytes treated with Aß had decreased expression of insulin receptor substrate-2 and reduced Akt-1 phosphorylation. CONCLUSIONS: Aß was made by adipose tissue cells in vitro at concentrations similar to in vivo measurements. Regulation of Aß production by glucose and insulin and effects of Aß on the insulin receptor pathway suggest similar cellular mechanisms may exist between neuronal dysfunction in Alzheimer disease and adipose dysfunction in type 2 diabetes.

Islet amyloid and type 2 diabetes: overproduction or inadequate clearance and detoxification?

A hallmark of type 2 diabetes is the reduction of pancreatic islet ß cell mass through induction of apoptosis and lack of regeneration. In most patients, ß cell dysfunction is associated with the presence of extracellular amyloid plaques adjacent to ß cells and intracellular toxic oligomers that are comprised of islet amyloid polypeptide (IAPP). In this issue of the JCI, three independent research groups reveal that a functional autophagy system normally prevents the accumulation of toxic IAPP oligomers in human IAPP-expressing murine models. Furthermore, mice expressing human IAPP but deficient for ß cell autophagy through genetic deletion of the autophagy initiator ATG7 developed ß cell apoptosis and overt diabetes. Together, these studies indicate that autophagy protects ß cells from the accumulation of toxic IAPP oligomers and suggest that enhancing autophagy may be a novel target for prevention of type 2 diabetes.