Differences in gut microbiota between Dutch and South-Asian Surinamese: potential implications for type 2 diabetes mellitus.

Gut microbiota, or the collection of diverse microorganisms in a specific ecological niche, are known to significantly impact human health. Decreased gut microbiota production of short-chain fatty acids (SCFAs) has been implicated in type 2 diabetes mellitus (T2DM) disease progression. Most microbiome studies focus on ethnic majorities. This study aims to understand how the microbiome differs between an ethnic majority (the Dutch) and minority (the South-Asian Surinamese (SAS)) group with a lower and higher prevalence of T2DM, respectively. Microbiome data from the Healthy Life in an Urban Setting (HELIUS) cohort were used. Two age- and gender-matched groups were compared: the Dutch (n = 41) and SAS (n = 43). Microbial community compositions were generated via DADA2. Metrics of microbial diversity and similarity between groups were computed. Biomarker analyses were performed to determine discriminating taxa. Bacterial co-occurrence networks were constructed to examine ecological patterns. A tight microbiota cluster was observed in the Dutch women, which overlapped with some of the SAS microbiota. The Dutch gut contained a more interconnected microbial ecology, whereas the SAS network was dispersed, i.e., contained fewer inter-taxonomic correlational relationships. Bacteroides caccae, Butyricicoccus, Alistipes putredinis, Coprococcus comes, Odoribacter splanchnicus, and Lachnospira were enriched in the Dutch gut. Haemophilus, Bifidobacterium, and Anaerostipes hadrus discriminated the SAS gut. All but Lachnospira and certain strains of Haemophilus are known to produce SCFAs. The Dutch gut microbiome was distinguished from the SAS by diverse, differentially abundant SCFA-producing taxa with significant cooperation. The dynamic ecology observed in the Dutch was not detected in the SAS. Among several potential gut microbial biomarkers, Haemophilus parainfluenzae likely best characterizes the ethnic minority group, which is more predisposed to T2DM. The higher prevalence of T2DM in the SAS may be associated with the gut dysbiosis observed.

PTK2-associated gene signature could predict the prognosis of IPF.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with a poor prognosis. Current/available clinical prediction tools have limited sensitivity and accuracy when evaluating clinical outcomes of IPF. Research has shown that focal adhesion kinase (FAK), produced by the protein tyrosine kinase 2 (PTK2) gene, is crucial in IPF development. FAK activation is a characteristic of lesional fibroblasts; Thus, FAK may be a valuable therapeutic target or prognostic biomarker for IPF. This study aimed to create a gene signature based on PTK2-associated genes and microarray data from blood cells to predict disease prognosis in patients with IPF. PTK2 levels were found to be higher in lung tissues of IPF patients compared to healthy controls, and PTK2 inhibitor Defactinib was found to reduce TGFß-induced FAK activation and increase α-smooth muscle actin. Although the blood PTK2 levels were higher in IPF patients, blood PTK level alone could not predict IPF prognosis. From 196 PTK2-associated genes, 11 genes were prioritized to create a gene signature (PTK2 molecular signature) and a risk score system using univariate and multivariate Cox regression analysis. Patients were divided into high-risk and low-risk groups using PTK2 molecular signature. Patients in the high-risk group experienced decreased survival rates compared to patients in the low-risk group across all discovery and validation cohorts. Further functional enrichment and immune cell proportion analyses revealed that the PTK2 molecular signature strongly reflected the activation levels of immune pathways and immune cells. These findings suggested that PTK2 is a molecular target of IPF and the PTK2 molecular signature is an effective IPF prognostic biomarker.

Isolated Abducens Nerve Palsy in the Setting of Isolated Sphenoid Sinusitis: A Case Report.

The cranial nerves (CNs) are responsible for multiple functions, including extraocular mobility, facial sensation and movement, hearing, mastication, tongue movement and sensation, and swallowing. Beyond these vital roles, they can also demonstrate importance in their diagnostic value. Isolated or combined palsies provide insights into potential localizations and various underlying etiologies, including stroke, tumor, and infections that may guide further neurological evaluation. CN VI, the abducens nerve, singularly innervates the lateral rectus muscle, which is responsible for the abduction of the eyes. Despite its long anatomic trajectory, making it susceptible to intracranial injury, an isolated abducens nerve palsy is extremely rare. The most common clinical presentation includes headache, diplopia, and the inability to abduct the afflicted eye. This case report introduces a 71-year-old female with a medical history of malignancy and pancytopenia who presented to the emergency room with complaints of ear pain and swelling and subsequently developed diplopia secondary to unilateral CN VI palsy. Magnetic resonance imaging (MRI) revealed isolated sphenoid sinusitis for which she was clinically asymptomatic. She was treated with a regimen of ampicillin-sulbactam, an oral anti-inflammatory agent, and a tapered course of methylprednisolone with a rapid and complete resolution of the abducens nerve palsy and sinusitis. Acute isolated diplopia is an unusual neurologic condition prompting the need for rapid and thorough investigation. Although exceedingly rare and infrequently cited in the literature, isolated abducens nerve palsies secondary to sphenoid sinusitis should be entertained in the differential diagnosis of this presentation.

Immunosuppression and Opportunistic Infections: A Rare Case Report of Nocardia Osteomyelitis of the Pelvis.

Patients with a long-standing history of immunosuppression are at significantly increased risk of opportunistic infections. One such group of organisms that may cause these types of infections includes the Nocardia genus, a gram-positive, filamentous rod that demonstrates a branching pattern, is urease-producing and has acid-fast properties. The disease profile of Nocardia varies with manifestations ranging from cutaneous infection to severe pulmonary or central nervous system (CNS) infections, and rarely, osteomyelitis. In this case report, we present an 87-year-old female with persistent left gluteal and lumbar pain, generalized body aches, chills, and fevers diagnosed with Nocardia asiatica osteomyelitis of the pelvis, likely secondary to dissemination from pulmonary cavitary disease in an immunosuppressed host with chronic neutropenia. On magnetic resonance imaging (MRI), the patient was found to have heterogeneous enhancement, central necrosis, and loss of cortical margins of the left iliac wing, alongside a rim-enhancing soft tissue mass from the left iliac bone into the left gluteal soft tissues and left paraspinal musculature representing an abscess. She was promptly treated with surgical irrigation and drainage with surgical wound cultures growing Nocardia asiatica. She received treatment with trimethoprim-sulfamethoxazole antibiotics with symptom improvement and is following up with an infectious disease physician outpatient. Management of osteomyelitis, like in this case, involves long-term antibiotics with the potential need for surgical intervention. There are few reported cases of extrapulmonary Nocardia infections, particularly osteomyelitis, demonstrating the importance of their inclusion in the literature to better serve patients to allow for timely intervention for rare and life-threatening conditions. In immunocompromised hosts, the differential diagnosis should include opportunistic infections and less common pathogens, especially in those with atypical presentations, including gluteal and leg pain.

Dysphagia: A Case Report of an Atypical Presentation of Statin-Induced Necrotizing Myositis.

Statin medications act by inhibiting the enzyme hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR), thus decreasing hepatic cholesterol synthesis. They are considered the mainstay treatment of hypercholesterolemia due to their tremendous efficacy and mortality benefit. Although generally well tolerated, statins may adversely affect skeletal muscle resulting in side effects ranging from mild myalgia to life-threatening necrotizing myositis. Statin-induced necrotizing autoimmune myositis is a rare yet devastating adverse effect that may occur shortly after initiation of therapy or after several years of use. Unfortunately, medication discontinuation has shown no impact on prevention or alleviation of symptoms. Though there is currently no definitive guidance for the treatment of this condition, corticosteroids are generally considered to be first line, via high-dose oral prednisone or intravenous methylprednisolone. In this case report, we discuss the case of a 72-year-old male with an unusual presentation of statin-induced necrotizing autoimmune myositis: dysphagia, weakness, and weight loss. His diagnosis was confirmed by muscle biopsy indicating necrotizing myositis and his serum was found to be strongly positive for anti-HMG-CoA reductase antibodies. This patient had a very brief history of statin use, but his primary care provider discontinued the medication a couple of months prior to symptom onset due to elevated liver function tests. He was treated with aggressive intravenous fluid hydration and intravenous corticosteroids during an extended inpatient hospital stay. He was discharged to a rehabilitation facility. This report demonstrates the importance of creating a wide differential for patients who present with fatigue, generalized weakness, and dysphagia. It is essential to always consider statin-induced necrotizing myositis if a patient has a history of statin use, even if the statin has been discontinued. Necrotizing myositis demands timely diagnosis and management to improve mortality.

Evaluation of Sex Differences in the Elasticity of Demand for Nicotine and Food in Rats.

INTRODUCTION: Animal studies can inform policy regarding nicotine levels in tobacco products and e-cigarette solutions. Increasing the price of nicotine-containing products decreases their use, but it is unknown how the relationship between price and consumption is affected by both sex and nicotine dose. METHODS: A behavioral economics procedure was used to determine the demand elasticity for nicotine in male and female rats. Demand elasticity describes the relationship between price and consumption. A high level of elasticity indicates that consumption is relatively sensitive to increases in price. The rats self-administered a low dose (0.01 mg/kg/inf) or a standard dose (0.03 mg/kg/inf) of nicotine for 9 days under a fixed-ratio (FR) 1 schedule. Then the price (FR schedule) of nicotine was increased, and a demand analysis was conducted. A similar study was conducted with palatable food pellets. RESULTS: There were no sex differences in nicotine or food intake under the FR1 schedule. However, demand for 0.03 mg/kg/inf of nicotine was more elastic in females than males. Demand for 0.01 mg/kg/inf of nicotine and food was more elastic in males than females. CONCLUSIONS: These findings indicate that there are no differences in nicotine and food intake between males and females when the price is low. When the price of nicotine or food is increased, males maintain their old level of intake longer than females when they have access to a standard dose of nicotine, and females maintain their intake longer when they have access to a low dose of nicotine or food. IMPLICATIONS: This behavioral economics analysis indicates that there is no sex difference in nicotine intake when the price of nicotine is low. Increasing the price of nicotine decreases nicotine intake in a dose- and sex-specific manner. Males maintain their old level of intake longer when they have access to a standard dose of nicotine and females when they have access to a low dose. This has implications for tobacco regulatory policy. In a regulatory environment where only low nicotine-containing products are allowed, increasing the price of nicotine products may lead to a greater decrease in nicotine use in males than females.