PPAR-γ activation enhances myelination and neurological recovery in premature rabbits with intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) results in periventricular inflammation, hypomyelination of the white matter, and hydrocephalus in premature infants. No effective therapy exists to prevent these disorders. Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists reduce inflammation, alleviate free radical generation, and enhance microglial phagocytosis, promoting clearance of debris and red blood cells. We hypothesized that activation of PPAR-γ would enhance myelination, reduce hydrocephalus, and promote neurological recovery in newborns with IVH. These hypotheses were tested in a preterm rabbit model of IVH; autopsy brain samples from premature infants with and without IVH were analyzed. We found that IVH augmented PPAR-γ expression in microglia of both preterm human infants and rabbit kits. The treatment with PPAR-γ agonist or PPAR-γ overexpression by adenovirus delivery further elevated PPAR-γ levels in microglia, reduced proinflammatory cytokines, increased microglial phagocytosis, and improved oligodendrocyte progenitor cell (OPC) maturation in kits with IVH. Transcriptomic analyses of OPCs identified previously unrecognized PPAR-γ-induced genes for purinergic signaling, cyclic adenosine monophosphate generation, and antioxidant production, which would reprogram these progenitors toward promoting myelination. RNA-sequencing analyses of microglia revealed PPAR-γ-triggered down-regulation of several proinflammatory genes and transcripts having roles in Parkinson's disease and amyotrophic lateral sclerosis, contributing to neurological recovery in kits with IVH. Accordingly, PPAR-γ activation enhanced myelination and neurological function in kits with IVH. This also enhanced microglial phagocytosis of red blood cells but did not reduce hydrocephalus. Treatment with PPAR-γ agonist might enhance myelination and neurological recovery in premature infants with IVH.

Outbreak of Listeriosis in South Africa Associated with Processed Meat.

BACKGROUND: An outbreak of listeriosis was identified in South Africa in 2017. The source was unknown. METHODS: We conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018. RESULTS: A total of 937 cases were identified, of which 465 (50%) were associated with pregnancy; 406 of the pregnancy-associated cases (87%) occurred in neonates. Of the 937 cases, 229 (24%) occurred in patients 15 to 49 years of age (excluding those who were pregnant). Among the patients in whom human immunodeficiency virus (HIV) status was known, 38% of those with pregnancy-associated cases (77 of 204) and 46% of the remaining patients (97 of 211) were infected with HIV. Among 728 patients with a known outcome, 193 (27%) died. Clinical isolates from 609 patients were sequenced, and 567 (93%) were identified as sequence type 6 (ST6). In a case-control analysis, patients with ST6 infections were more likely to have eaten polony (a ready-to-eat processed meat) than those with non-ST6 infections (odds ratio, 8.55; 95% confidence interval, 1.66 to 43.35). Polony and environmental samples also yielded ST6 isolates, which, together with the isolates from the patients, belonged to the same core-genome multilocus sequence typing cluster with no more than 4 allelic differences; these findings showed that polony produced at a single facility was the outbreak source. A recall of ready-to-eat processed meat products from this facility was associated with a rapid decline in the incidence of L. monocytogenes ST6 infections. CONCLUSIONS: This investigation showed that in a middle-income country with a high prevalence of HIV infection, L. monocytogenes caused disproportionate illness among pregnant girls and women and HIV-infected persons. Whole-genome sequencing facilitated the detection of the outbreak and guided the trace-back investigations that led to the identification of the source.

Electrochemical Approach for the Synthesis of Ultrasmall Cu13 Clusters and Their Application in the Detection of Endotoxin.

Ultrasmall metal nanoclusters are attractive for their size-dependent optical and electrochemical properties. Here, blue-emitting copper clusters stabilized with cetyltrimethylammonium bromide (CTAB) are synthesized using an electrochemical approach. The electrospray ionization (ESI) analysis reveals that the cluster has 13 copper atoms in the core. The clusters are then used for the electrochemical detection of endotoxin─a bacterial toxin in Gram-negative bacteria. Differential pulse voltammetry (DPV) is used to detect endotoxins with high selectivity and sensitivity. It shows a lower detection limit of 100 ag mL-1 with a linear range of 100 ag mL-1 to 10 ng mL-1. The sensor is efficient for detecting endotoxins from human blood serum samples.

Cu2+-Mediated Aggregation of Gold Nanoparticles as an Optical Probe for the Detection of Endotoxin.

Endotoxins or lipopolysaccharides (LPS) present in the outer layer of Gram-negative bacteria (GNB) are responsible for bacterial toxicity. It is an environmental hazard that everyone is exposed to daily to various extents. Due to its potent toxicity, quantitative detection with very high sensitivity is essential in the food, medical, and pharmaceutical industries. Herein, we report an optical nanosensor for the rapid and sensitive detection of LPS and GNB based on the Cu2+-mediated aggregation of gold nanoparticles (Cu@AuNPs). The sensor detects LPS within a linear range of 20 ag/mL to 20 ng/mL with a lower detection limit of 0.2 ag/mL. The sensor could successfully recover spiked endotoxin in grape juice with a percentage error of ±0.2, confirming its application in the food industry. The sensor could also distinguish Gram-negative bacteria from Gram-positive bacteria, and the selectivity of the Cu@AuNP sensor toward GNB is utilized to detect Escherichia coli in wastewater. The rapid detection of E. coli without any pretreatment is a promising strategy in water analysis.

A review of -multidrug-resistant Enterobacteriaceae in a neonatal unit in Johannesburg, South Africa.

BACKGROUND: Multi-drug resistant organisms are an increasingly important cause of neonatal sepsis. AIM: This study aimed to review neonatal sepsis caused by multi-drug resistant Enterobacteriaceae (MDRE) in neonates in Johannesburg, South Africa. METHODS: This was a cross sectional retrospective review of MDRE in neonates admitted to a tertiary neonatal unit between 1 January 2013 and 31 December 2015. RESULTS: There were 465 infections in 291 neonates. 68.6% were very low birth weight (< 1500 g). The median age of infection was 14.0 days. Risk factors for MDRE included prematurity (p = 0.01), lower birth weight (p = 0.04), maternal HIV infection (p = 0.02) and oxygen on day 28 (p < 0.001). The most common isolate was Klebsiella pneumoniae (66.2%). Total MDRE isolates increased from 0.39 per 1000 neonatal admissions in 2013 to 1.4 per 1000 neonatal admissions in 2015 (p < 0.001). There was an increase in carbapenem-resistant Enterobacteriaceae (CRE) from 2.6% in 2013 to 8.9% in 2015 (p = 0.06). Most of the CRE were New Delhi metallo-ß lactamase- (NDM) producers. The all-cause mortality rate was 33.3%. Birth weight (p = 0.003), necrotising enterocolitis (p < 0.001) and mechanical ventilation (p = 0.007) were significantly associated with mortality. Serratia marcescens was isolated in 55.2% of neonates that died. CONCLUSIONS: There was a significant increase in MDRE in neonatal sepsis during the study period, with the emergence of CRE. This confirms the urgent need to intensify antimicrobial stewardship efforts and address infection control and prevention in neonatal units in LMICs. Overuse of broad- spectrum antibiotics should be prevented.

Were all carbapenemases created equal? Treatment of NDM-producing extensively drug-resistant Enterobacteriaceae: a case report and literature review.

PURPOSE: There is currently a paucity of published literature focused on the treatment of infections caused by NDM-producing organisms. METHODS: We describe a case of a bacteraemia caused by an extensively drug-resistant (XDR) New Delhi metallo-ß-lactamase (NDM)-producing Serratia marcescens and review the treatment options for XDR NDM-producing Enterobacteriaceae. RESULTS: Infections caused by New Delhi beta-lactamase (NDM)-producing Enterobacteriaceae are becoming increasingly prevalent worldwide. The presence of the enzyme results in multidrug-resistant and extensively drug-resistant phenotypes which often pose a treatment challenge. Despite this challenge, case reports and series have demonstrated good clinical outcomes with numerous treatment options in comparison to infections due to KPC-producing Enterobacteriaceae. CONCLUSIONS: Further good-quality research focused on the treatment of NDM-producing Enterobacteriaceae is warranted.

Tumor Volume Growth Rates and Doubling Times during Active Surveillance of IDH-mutant Low-Grade Glioma.

PURPOSE: Isocitrate dehydrogenase-mutant (IDH-mt) gliomas are incurable primary brain tumors characterized by a slow-growing phase over several years followed by a rapid-growing malignant phase. We hypothesized that tumor volume growth rate (TVGR) on MRI may act as an earlier measure of clinical benefit during the active surveillance period. EXPERIMENTAL DESIGN: We integrated three-dimensional volumetric measurements with clinical, radiologic, and molecular data in a retrospective cohort of IDH-mt gliomas that were observed after surgical resection in order to understand tumor growth kinetics and the impact of molecular genetics. RESULTS: Using log-linear mixed modeling, the entire cohort (n = 128) had a continuous %TVGR per 6 months of 10.46% [95% confidence interval (CI), 9.11%-11.83%] and a doubling time of 3.5 years (95% CI, 3.10-3.98). High molecular grade IDH-mt gliomas, defined by the presence of homozygous deletion of CDKN2A/B, had %TVGR per 6 months of 19.17% (95% CI, 15.57%-22.89%) which was significantly different from low molecular grade IDH-mt gliomas with a growth rate per 6 months of 9.54% (95% CI, 7.32%-11.80%; P < 0.0001). Using joint modeling to comodel the longitudinal course of TVGR and overall survival, we found each one natural logarithm tumor volume increase resulted in more than a 3-fold increase in risk of death (HR = 3.83; 95% CI, 2.32-6.30; P < 0.0001). CONCLUSIONS: TVGR may be used as an earlier measure of clinical benefit and correlates well with the WHO 2021 molecular classification of gliomas and survival. Incorporation of TVGR as a surrogate endpoint into future prospective studies of IDH-mt gliomas may accelerate drug development.

Imaging 2-hydroxyglutarate and other brain oncometabolites pertinent to critical genomic alterations in brain tumors.

The 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) and recent smaller annual updates have shown that alterations in tumor genetics are essential to determining tumor diagnosis, biological activity, and potential treatment options. This review summarizes the most important mutations and oncometabolites, with a focus on the central role played by 2-hydroxyglutarate in isocitrate dehydrogenase mutant tumors, as well as their corresponding imaging counterparts using standard and advanced imaging techniques.

Label-free detection of endotoxin and gram-negative bacteria from water using copper (I) oxide anchored reduced graphene oxide.

Bacterial contamination is a serious concern for health and environmental safety. The major toxic effect arises from the endotoxin or lipopolysaccharide (LPS) attached to the cell wall of the gram-negative bacteria. Ultrasensitive endotoxin detection is of supreme importance in sustaining food, clinical and pharmaceutical safety. Herein we report a simple electrochemical detection platform using reduced graphene oxide (rGO) combined with cuprous oxide nanoparticles for the ultrasensitive detection of LPS. The sensor uses polymyxin B (PmB) to achieve the selective response towards LPS. The sensor showed a lower detection limit (LOD) of 10 agmL-1 with linearity from 10 agmL-1 to 10 ngmL-1. Detection of LPS from whole blood is also carried out with excellent sensitivity. The sensor showed excellent recovery rates in whole blood, pointing to the capability of using the sensor in real-life clinical analysis. The sensor detects Gram-negative bacteria from sewage water with a rapid response time, indicating the effectiveness of the sensor in water quality analysis.

A Rare Case of Relapsed Sarcoidosis Presenting As Severe Thrombocytopenia Associated With Intracerebral Hemorrhage Due to Bone Marrow Involvement.

Sarcoidosis is a systemic granulomatous disease characterized by the hyperactivation of CD4 T cells, CD8 T cells, and macrophages. Clinical presentations of sarcoidosis are highly variable. Sarcoidosis is unknown in its etiology, but it suggests it may result from exposure to specific environmental agents in genetically susceptible people. Sarcoidosis commonly involves the lungs and lymphoid system. Bone marrow involvement in sarcoidosis is uncommon. Sarcoidosis rarely results in intracerebral hemorrhage due to severe thrombocytopenia secondary to bone marrow involvement. We present the case of a 72-year-old woman who has been in remission from sarcoidosis for 15 years and developed intracerebral hemorrhage secondary to severe thrombocytopenia due to sarcoidosis recurrence in the bone marrow. The patient presented to the emergency department with a generalized, non-blanching petechiae rash and nose and gum bleeding. Her labs showed a platelet count of less than 10.000/mcL, and computed tomography (CT) showed intracerebral hemorrhage. A bone marrow biopsy revealed a small, non-caseating granuloma indicative of a sarcoidosis relapse in the bone marrow.

BK-Virus-Induced Hemorrhagic Cystitis in a Patient With Graft-Versus-Host Disease.

The BK virus is a polyomavirus known to particularly affect transplant recipients. An important complication caused by BK virus infection in bone marrow transplant patients is hemorrhagic cystitis. We present a 31-year-old male with a history of bone marrow transplantation complicated by graft-versus-host disease (GVHD) and was diagnosed with BK virus-related hemorrhagic cystitis. He presented with gross hematuria and suprapubic and penile pain for one week. He has a significant past medical history of acute B-cell lymphocytic leukemia for which he has successfully undergone allogenic bone marrow transplantation, which was complicated by GVHD. Imaging revealed significant bladder wall thickening which prompted an evaluation for BK virus-induced hemorrhagic cystitis. A urinary specimen was sent for BK virus polymerase chain reaction (PCR) which was strongly positive, confirming the infection. He was managed supportively throughout his hospitalization and improved with symptomatic management alone. Our case demonstrates one of the main complications caused by the BK virus in allogeneic bone marrow transplant patients in the setting of GVHD and is an important differential to keep in mind when treating patients presenting with hematuria after bone marrow transplantation.

IgA Vasculitis Followed by IgA Nephropathy Without an Identifiable Trigger: The Same Disease or a Spectrum of Related Conditions?

IgA vasculitis and IgA nephropathy are characterized by IgA deposition in blood vessels and glomerular mesangium, respectively. The former is far more common in the pediatric population, while the latter presents more often in adulthood. A consensus regarding whether these two conditions are manifestations of the same disease that occurs on a spectrum has not yet been reached, and, to our knowledge, no clinical trials to address this question have been conducted. Here, we describe a 27-year-old patient who presented to the emergency department multiple times before being diagnosed with IgA vasculitis with no identifiable trigger and soon after developed IgA nephropathy. This case highlights the importance of ruling out these conditions, especially IgA vasculitis, in adults presenting with a petechial rash, but also the need for studies that investigate whether and how these conditions are related so that patients can be appropriately diagnosed and treated as efficiently as possible.

Case Report of Painless Obstructive Jaundice: A Rare First Presentation of Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) is a very aggressive type of lung cancer that is of neuroendocrine origin. Because of the high levels of circulating tumor cells, it has a very high rate of metastasis. Obstructive jaundice as the initial manifestation of small cell lung carcinoma is rare. Most of the cases are due to extrahepatic cholestasis by biliary duct obstruction. The biliary duct obstruction may be secondary to metastasis to lymph nodes or pancreatic head metastasis. Obstructive jaundice secondary to intrahepatic cholestasis is even rarer. A 75-year-old male presented to the emergency department (ED) with a complaint of new-onset painless jaundice that his dentist incidentally detected. Examination revealed a mass in the right upper quadrant (RUQ) of the abdomen. Computed tomography (CT) angiography of the abdomen, pancreas, and pelvis shows innumerable hepatic hypodensities highly suspicious for metastatic disease. However, there was no extrahepatic dilatation or pancreatic mass. He was diagnosed with diffuse metastasis of small cell lung carcinoma (SCLC) by needle biopsy of the liver. He developed acute kidney injury and liver damage and thus compromised chemotherapy for SCLC. Later, the patient chose comfort care and passed away the next day. To our knowledge, this is the second reported case of SCLC initially presenting as obstructive jaundice secondary intrahepatic cholestasis by diffuse liver metastases.

Evaluation of Xpert Carba-R for detecting carbapenemase-producing organisms in South Africa.

This study evaluated the performance of the Xpert Carba-R assay for detecting the five common carbapenemases in carbapenemase-producing organisms in Johannesburg, South Africa between April 2021 and September 2021. The assay demonstrated 98% sensitivity and 97% specificity. It was also able to detect all the carbapenemases in double carbapenemase producers, as well as carbapenemases in non-fermenter organisms. The Xpert Carba-R assay, therefore, allows the rapid (< 1 h) and accurate identification of the common carbapenemases in pure bacterial cultures and rectal swabs. This assay can aid in the timeous institution of appropriate treatment and infection prevention and control measures.

A Case of Chronic Mesenteric Ischemia Due to Celiac and Mesenteric Artery Thrombosis.

Chronic mesenteric ischemia (CMI) is uncommon and accounts for approximately 5% of cases. CMI presents with non-specific symptoms, making it difficult to diagnose, and requires complex management involving interprofessional teams. We present the case of a 66-year-old female who presented with postprandial abdominal pain, vomiting, sitophobia, and weight loss. Investigations showed raised inflammatory markers, and plain film X-ray and endoscopy showed no significant findings. CT angiogram showed celiac and mesenteric artery thrombosis. The patient proceeded to have endovascular revascularization. With this case, we highlight the importance of considering CMI in an elderly patient with a history of microvascular disease or risk factors presenting with postprandial abdominal pain and weight loss. Early diagnosis and timely intervention are imperative for a good prognosis.

Arcanobacterium haemolyticum: A case series.

Arcanobacterium haemolyticum formerly known as Corynebacteria haemolyticum is a Gram positive bacilli. It is a fastidious, facultative anerobic, catalase negative, beta haemolytic and non motile bacterium. Gram positive bacilli are usually considered to be non-pathogenic as the majority are part of normal flora of human skin and mucous membranes. Hence, diagnosis of such infection and its treatment may be delayed by a failure of recognition. However, this bacterium has been implicated in wound, superficial and deep-seated soft tissue infections, endocarditis, osteomyelitis, meningitis, pneumonia, and also septicemia. The early diagnostic evaluation of this organism is emphasized. We report a case series which illustrates the significance of Arcanobacterium haemolyticum in skin and soft tissue infections.

Dropped Gallstone Mimicking Retroperitoneal Tumor 5 Years After Laparoscopic Cholecystectomy Posing a Diagnostic Challenge.

Laparoscopic cholecystectomy is the standard treatment for cholecystitis. The major complications associated with laparoscopic cholecystectomy include bleeding, abscess formation, biliary injury with bile leakage, and bowel injury. Gallbladder perforation and subsequent stone spillage are not uncommon in laparoscopic cholecystectomy. The majority of these spilled stones remain clinically silent. But sometimes they can cause abscesses and make diagnosis challenging especially when it occurs years after the procedure and when the abscess form in uncommon sites. A 66-year-old female with a history of laparoscopic cholecystectomy presented with aggravating abdominal pain in the right upper quadrant (RUQ). The CT abdomen revealed a mass in the retroperitoneum behind the hepatic flexure. Upon further examination, follow-up CT scans, and biopsy repeatedly failed to exclude malignancy, so it was suggested that the patient undergo surgical removal of the mass. The pathological analysis of the excised mass revealed that it was a dropped gallstone from the procedure that triggered an inflammatory reaction. Dropped gallstones should be considered as a differential diagnosis in a patient with a history of laparoscopic cholecystectomy presenting with an abdominal or retroperitoneal abscess, as a failure of early recognition puts the patient at risk of undergoing unnecessary and invasive procedures.

Retrospective analysis of Vitek®2 performance compared to manual broth micro-dilution for colistin susceptibility testing of Acinetobacter baumanniicomplex isolates in South Africa.

The manual broth micro-dilution (mBMD) is the recommended reference method for colistin minimum inhibitory concentration determination; however, it is not as readily available in South Africa as the Vitek®2. This retrospective study compared the performance of Vitek®2 against mBMD in determining the colistin minimum inhibitory concentration of 337 extensively drug-resistant Acinetobacter baumannii complex isolates. Vitek®2 yielded a categorical agreement of 89%, an essential agreement of 56%, a major error rate of 8% and a very major error rate of 55%. The Vitek®2 is not an alternative to mBMD for colistin susceptibility testing.

Diagnostic challenges with accurate identification of Listeria monocytogenes isolates from food and environmental samples in South Africa.

Background: The 2017-2018 listeriosis outbreak in South Africa warranted testing for Listeria monocytogenes in food products and processing environments. Diagnostic tests are needed to accurately differentiate L. monocytogenes from other Listeria species. Objective: The study assessed the performance of the commonly used tests in our setting to accurately identify L. monocytogenes. Methods: The study was conducted in a public health laboratory in South Africa. Cultured isolates from food and environmental samples were tested both prospectively and retrospectively between August 2018 and December 2018. Isolates were phenotypically identified using tests for detecting ß-haemolysis, Christie-Atkins-Munch-Peterson, alanine arylamidase (AlaA), mannosidase, and xylose fermentation. Listeria monocytogenes isolates were identified using automated systems, Microscan Walkaway Plus 96, Vitek® MS, Vitek® 2 and Surefast Listeria monocytogenes PLUS PCR. All results were compared to whole-genome sequencing results. Results: ß-haemolysis and Christie-Atkins-Munch-Peterson tests gave delayed positivity or were negative for L. monocytogenes and falsely positive for one strain of Listeria innocua. The AlaA enzyme and Colorex Listeria agar lacked specificity for L. monocytogenes identification. Based on a few phenotypic test results, an aberrant L. monocytogenes strain and Listeria seeligeri strain were reported. All automated platforms overcalled L. monocytogenes in place of other Listeria species. Conclusion: No test was ideal in differentiating Listeria species. This is an issue in resource-limited settings where these tests are currently used. Newer technologies based on enzyme-linked immunosorbent assay and other molecular techniques specific to L. monocytogenes detection need to be investigated.

Hemophagocytic Lymphohistiocytosis in a Patient With Post-acute COVID-19 Infection.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation with extensive inflammation and tissue destruction due to abnormal immune activation. Post-COVID-19 patients who have recovered with negative serologic tests may also present with secondary HLH, an unusual finding that our case demonstrates. A 73-year-old male with a notable past medical history of fall COVID-19 infection approximately 11 months prior presented initially to emergency services with a chief complaint of high fevers, lethargy, and progressive changes in mentation gradually progressive over the last 5 months' duration. This presentation was concerning for HLH in view of the patient's high H score and clinical suspicion for HLH, and he was initiated on dexamethasone 20 mg daily. intravenous immune globulin (IVIG) protocol was also trialed, despite which the patient continued to deteriorate before expiring during the course of the hospitalization. sHLH following COVID-19 infection remains a poorly understood phenomenon. The severity of the COVID-19 infection does not appear to be related to one's predisposition to develop sHLH. The mortality of HLH remains high even with appropriate therapy.