Host-derived fatty acids activate type VII secretion in Staphylococcus aureus.

The type VII secretion system (T7SS) of Staphylococcus aureus is a multiprotein complex dedicated to the export of several virulence factors during host infection. This virulence pathway plays a key role in promoting bacterial survival and the long-term persistence of staphylococcal abscess communities. The expression of the T7SS is activated by bacterial interaction with host tissues including blood serum, nasal secretions, and pulmonary surfactant. In this work we identify the major stimulatory factors as host-specific cis-unsaturated fatty acids. Increased T7SS expression requires host fatty acid incorporation into bacterial biosynthetic pathways by the Saureus fatty acid kinase (FAK) complex, and FakA is required for virulence. The incorporated cis-unsaturated fatty acids decrease Saureus membrane fluidity, and these altered membrane dynamics are partially responsible for T7SS activation. These data define a molecular mechanism by which Saureus cells sense the host environment and implement appropriate virulence pathways.

How often does computed tomography (CT) of the brain demonstrate a cause for psychosis? A 7-year retrospective study at a tertiary metropolitan hospital.

OBJECTIVES: The aim of the study was to determine the diagnostic yield of computed tomography (CT) of the brain for the investigation of psychosis. METHODS: CT brain requests describing psychosis over a 7-year period at a 500-bed major metropolitan hospital were identified retrospectively. Patients were excluded if they were aged greater than 50 years or if the CT request described focal neurological findings on examination, trauma/falls or known brain tumour, demyelinating disorder, encephalopathy, seizure disorder, congenital brain anomaly, stroke or traumatic brain injury. RESULTS: A total of 805 patients meeting the inclusion and exclusion criteria were identified, representing the largest published study on this topic. Only 0.4% of patients (3 out of 805) had a potential cause for psychosis demonstrated on CT. None of these patients had their management altered as a result. An additional 0.6% of patients (5 out of 805) had significant pathology that was deemed unrelated to their psychosis. CONCLUSIONS: The diagnostic value of CT in the setting of psychosis was found to be extremely low in patients meeting the inclusion and exclusion criteria. Given the risk of ionising radiation and the expenditure of time and cost, more judicious use of CT is suggested.

Structural basis for the geometry-driven localization of a small protein.

In bacteria, certain shape-sensing proteins localize to differently curved membranes. During sporulation in Bacillus subtilis, the only convex (positively curved) surface in the cell is the forespore, an approximately spherical internal organelle. Previously, we demonstrated that SpoVM localizes to the forespore by preferentially adsorbing onto slightly convex membranes. Here, we used NMR and molecular dynamics simulations of SpoVM and a localization mutant (SpoVM(P9A)) to reveal that SpoVM's atypical amphipathic α-helix inserts deeply into the membrane and interacts extensively with acyl chains to sense packing differences in differently curved membranes. Based on binding to spherical supported lipid bilayers and Monte Carlo simulations, we hypothesize that SpoVM's membrane insertion, along with potential cooperative interactions with other SpoVM molecules in the lipid bilayer, drives its preferential localization onto slightly convex membranes. Such a mechanism, which is distinct from that used by high curvature-sensing proteins, may be widely conserved for the localization of proteins onto the surface of cellular organelles.

Metastatic Cellular Blue Nevus: A Rare Case With Metastasis Beyond Regional Nodes.

In this study, we present a rare case of a 35-year-old man with a long-standing blue-black lesion on his left hand with subsequent infraclavicular and axillary lymph node tumor deposits. The hand lesion and lymph nodes were excised revealing histological, immunohistochemical, and molecular findings consistent with cellular blue nevus. Despite nonregional lymph node involvement, there has been no progression at 12-months follow-up. This is an index case of a cellular blue nevus with metastasis to both regional and nonregional lymph nodes. The lack of atypical/malignant features in this lesion makes the metastatic behavior extraordinary, and hence the prognosis of lesions of this type is indeterminate.

Identifying and assessing strategies for evaluating the impact of mobile eye health units on health outcomes.

OBJECTIVE: To identify and assess strategies for evaluating the impact of mobile eye health units on health outcomes. DESIGN: Systematic literature review. SETTING: Worldwide. PARTICIPANTS: Peer-reviewed journal articles that included the use of a mobile eye health unit. MAIN OUTCOME MEASURE(S): Journal articles were included if outcome measures reflected an assessment of the impact of a mobile eye health unit on health outcomes. RESULTS: Six studies were identified with mobile services offering diabetic retinopathy screening (three studies), optometric services (two studies) and orthoptic services (one study). CONCLUSION: This review identified and assessed strategies in existing literature used to evaluate the impact of mobile eye health units on health outcomes. Studies included in this review used patient outcomes (i.e. disease detection, vision impairment, treatment compliance) and/or service delivery outcomes (i.e. cost per attendance, hospital transport use, inappropriate referrals, time from diabetic retinopathy photography to treatment) to evaluate the impact of mobile eye health units. Limitations include difficulty proving causation of specific outcome measures and the overall shortage of impact evaluation studies. Variation in geographical location, service population and nature of eye care providers limits broad application.

Characterization of affinity-purified isoforms of Acinetobacter calcoaceticus Y1 glutathione transferases.

Glutathione transferases (GST) were purified from locally isolated bacteria, Acinetobacter calcoaceticus Y1, by glutathione-affinity chromatography and anion exchange, and their substrate specificities were investigated. SDS-polyacrylamide gel electrophoresis revealed that the purified GST resolved into a single band with a molecular weight (MW) of 23 kDa. 2-dimensional (2-D) gel electrophoresis showed the presence of two isoforms, GST1 (pI 4.5) and GST2 (pI 6.2) with identical MW. GST1 was reactive towards ethacrynic acid, hydrogen peroxide, 1-chloro-2,4-dinitrobenzene, and trans,trans-hepta-2,4-dienal while GST2 was active towards all substrates except hydrogen peroxide. This demonstrated that GST1 possessed peroxidase activity which was absent in GST2. This study also showed that only GST2 was able to conjugate GSH to isoproturon, a herbicide. GST1 and GST2 were suggested to be similar to F0KLY9 (putative glutathione S-transferase) and F0KKB0 (glutathione S-transferase III) of Acinetobacter calcoaceticus strain PHEA-2, respectively.

Metformin in Systemic Lupus Erythematosus: Investigating Cardiovascular Impact and Nephroprotective Effects in Lupus Nephritis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by widespread organ inflammation. Metformin, commonly used for diabetes mellitus type 2, has been explored for its anti-inflammatory potential in SLE. This study investigates the association of metformin use on renal and cardiovascular outcomes in patients with SLE. METHODS: This is a retrospective study. We used the multicenter research network (TriNetX) database from 88 health care organizations globally. Patients with SLE aged 18 and above, admitted between January 1, 2014, and April 21, 2024, were included. Propensity score matching compared patients with SLE on metformin with those not on metformin, considering demographics, laboratory results, comorbidities, and baseline medication use. The study assessed outcomes, including lupus nephritis (LN), chronic kidney disease (CKD), and major adverse cardiovascular events (MACEs) at one and five years after SLE diagnosis. RESULTS: We identified 9,178 patients with SLE on metformin and 78,983 patients with SLE not on metformin. After propensity score matching, patients with SLE on metformin had higher levels of hemoglobin A1C, whereas patients not on metformin had higher levels of urea nitrogen. When comparing both groups, the risk of developing LN (risk ratio [RR] = 1.70 [1.17-2.41]; P = 0.004), CKD (RR = 1.27 [1.07-1.52]; P = 0.007), and MACEs (RR = 1.21 [1.00-1.46]; P = 0.04) was significantly higher among patients not on metformin at one year after SLE diagnosis. After five years, the risk of LN and CKD was also higher in patients with SLE not on metformin. MACE risk was no longer significant after five years of diagnosis between both groups. CONCLUSION: Patients with SLE not on metformin have a higher risk of developing LN, CKD, and MACEs compared with patients treated with metformin. Metformin's anti-inflammatory potential offers promise as a complementary therapy for SLE. Nonetheless, further research and clinical trials are needed to clarify its mechanisms, optimal dosage, and long-term effects.

Atypical Adult-Onset Still's Disease Presenting With Seizures and Myocarditis Complicated by Macrophage Activation Syndrome.

Adult-onset Still's disease (AOSD) is a rare multi-systemic inflammatory disorder characterized by high spiking fevers, nonpruritic, salmon-colored rash, and severe polyarthralgia. Laboratory features typically include elevation in white blood cells, liver enzymes, and ferritin. Central nervous system and cardiac involvements, particularly myocarditis, are rare. Macrophage activation syndrome (MAS) is a well-described complication of AOSD, leading to a high mortality rate. Herein, we describe a case of AOSD complicated by MAS in a 32-year-old male presenting with atypical clinical manifestations, including recurrent seizures, scaly, pruritic, and hyperpigmented rash, and right heart failure due to lymphocytic myocarditis. The patient exhibited a delayed onset of fever, leukocytosis, and transaminitis that initially deterred eligibility for Yamaguchi criteria for AOSD. Bone marrow and lymph node biopsies did not show malignancy, infection, or hemophagocytosis. However, soluble interleukin-2 receptor alpha or soluble CD-25 was elevated. The patient experienced significant improvement on combination therapy of anakinra, methotrexate, and stress-dose steroids. HScore was later indicative of a high probability for MAS. Outpatient management involved prednisone, cyclosporine, and canakinumab for MAS. Seizure and myocarditis are possible presenting features of atypical AOSD. Early recognition of non-criteria AOSD and MAS and prompt initiation of therapy may prevent mortality.

CTP for the Screening of Vasospasm and Delayed Cerebral Ischemia in Aneurysmal SAH: A Systematic Review and Meta-analysis.

BACKGROUND: Delayed cerebral ischemia and vasospasm are the most common causes of late morbidity following aneurysmal SAH, but their diagnosis remains challenging. PURPOSE: This systematic review and meta-analysis investigated the diagnostic performance of CTP for detection of delayed cerebral ischemia and vasospasm in the setting of aneurysmal SAH. DATA SOURCES: Studies evaluating the diagnostic performance of CTP in the setting of aneurysmal SAH were searched on the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Clinical Answers, Cochrane Methodology Register, Ovid MEDLINE, EMBASE, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects, Health Technology Assessment, National Health Service Economic Evaluation Database, PubMed, and Google Scholar from their inception to September 2023. STUDY SELECTION: Thirty studies were included, encompassing 1786 patients with aneurysmal SAH and 2302 CTP studies. Studies were included if they compared the diagnostic accuracy of CTP with a reference standard (clinical or radiologic delayed cerebral ischemia, angiographic spasm) for the detection of delayed cerebral ischemia or vasospasm in patients with aneurysmal SAH. The primary outcome was accuracy for the detection of delayed cerebral ischemia or vasospasm. DATA ANALYSIS: Bivariate random effects models were used to pool outcomes for sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Subgroup analyses for individual CTP parameters and early-versus-late study timing were performed. Bias and applicability were assessed using the modified QUADAS-2 tool. DATA SYNTHESIS: For assessment of delayed cerebral ischemia, CTP demonstrated a pooled sensitivity of 82.1% (95% CI, 74.5%-87.8%), specificity of 79.6% (95% CI, 73.0%-84.9%), positive likelihood ratio of 4.01 (95% CI, 2.94-5.47), and negative likelihood ratio of 0.23 (95% CI, 0.12-0.33). For assessment of vasospasm, CTP showed a pooled sensitivity of 85.6% (95% CI, 74.2%-92.5%), specificity of 87.9% (95% CI, 79.2%-93.3%), positive likelihood ratio of 7.10 (95% CI, 3.87-13.04), and negative likelihood ratio of 0.16 (95% CI, 0.09-0.31). LIMITATIONS: QUADAS-2 assessment identified 12 articles with low risk, 11 with moderate risk, and 7 with a high risk of bias. CONCLUSIONS: For delayed cerebral ischemia, CTP had a sensitivity of >80%, specificity of >75%, and a low negative likelihood ratio of 0.23. CTP had better performance for the detection of vasospasm, with sensitivity and specificity of >85% and a low negative likelihood ratio of 0.16. Although the accuracy offers the potential for CTP to be used in limited clinical contexts, standardization of CTP techniques and high-quality randomized trials evaluating its impact are required.

The clinical relevance of MOG antibody testing in cerebrospinal fluid.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is diagnosed by serum MOG-immunoglobulin G (MOG-IgG) in association with typical demyelination. 111/1127 patients with paired CSF/serum samples were seropositive for MOG-IgG. Only 7/1016 (0.7%) seronegative patients had CSF-restricted MOG-IgG. While 3/7 patients had longitudinally extensive transverse myelitis, four had a confirmed alternate diagnosis (three multiple sclerosis, one CNS vasculitis). In a national referral setting, CSF-restricted MOG-IgG had a low sensitivity (2.63%, 95%CI 0.55-7.50%) and low positive predictive value (1.97%, 95%CI 0.45-8.13%). We strongly recommend serum as the preferred diagnostic biospecimen, and urge caution in the interpretation of CSF-restricted MOG-IgG in patients without clinico-radiological features consistent with MOGAD.

Small proteins link coat and cortex assembly during sporulation in Bacillus subtilis.

Mature spores of the bacterium Bacillus subtilis are encased by two concentric shells: an inner shell (the 'cortex'), made of peptidoglycan; and an outer proteinaceous shell (the 'coat'), whose basement layer is anchored to the surface of the developing spore via a 26-amino-acid-long protein called SpoVM. During sporulation, initiation of cortex assembly depends on the successful initiation of coat assembly, but the mechanisms that co-ordinate the morphogenesis of both structures are largely unknown. Here, we describe a sporulation pathway involving SpoVM and a 37-amino-acid-long protein named 'CmpA' that is encoded by a previously un-annotated gene and is expressed under control of two sporulation-specific transcription factors (σ(E) and SpoIIID). CmpA localized to the surface of the developing spore and deletion of cmpA resulted in cells progressing through the sporulation programme more quickly. Overproduction of CmpA did not affect normal growth or cell division, but delayed entry into sporulation and abrogated cortex assembly. In those cells that had successfully initiated coat assembly, CmpA was removed by a post-translational mechanism, presumably in order to overcome the sporulation inhibition it imposed. We propose a model in which CmpA participates in a developmental checkpoint that ensures the proper orchestration of coat and cortex morphogenesis by repressing cortex assembly until coat assembly successfully initiates.

Spatial pattern in Antarctica: what can we learn from Antarctic bacterial isolates?

A range of small- to moderate-scale studies of patterns in bacterial biodiversity have been conducted in Antarctica over the last two decades, most suggesting strong correlations between the described bacterial communities and elements of local environmental heterogeneity. However, very few of these studies have advanced interpretations in terms of spatially associated patterns, despite increasing evidence of patterns in bacterial biogeography globally. This is likely to be a consequence of restricted sampling coverage, with most studies to date focusing only on a few localities within a specific Antarctic region. Clearly, there is now a need for synthesis over a much larger spatial to consolidate the available data. In this study, we collated Antarctic bacterial culture identities based on the 16S rRNA gene information available in the literature and the GenBank database (n > 2,000 sequences). In contrast to some recent evidence for a distinct Antarctic microbiome, our phylogenetic comparisons show that a majority (~75 %) of Antarctic bacterial isolates were highly similar (≥99 % sequence similarity) to those retrieved from tropical and temperate regions, suggesting widespread distribution of eurythermal mesophiles in Antarctic environments. However, across different Antarctic regions, the dominant bacterial genera exhibit some spatially distinct diversity patterns analogous to those recently proposed for Antarctic terrestrial macroorganisms. Taken together, our results highlight the threat of cross-regional homogenisation in Antarctic biodiversity, and the imperative to include microbiota within the framework of biosecurity measures for Antarctica.

Race and Gender on the Mortality of Giant Cell Arteritis in Hospitalized Patients: A 15-Year National Inpatient Study.

BACKGROUND: Critical appraisal of mortality in giant cell arteritis (GCA) through a racial lens is imperative as gender and racial disparities remain a global healthcare concern. OBJECTIVE: To analyze the impact of race and gender on the mortality of GCA in United States (US)-hospitalized patients. METHODS: In this retrospective cohort study, the National Inpatient Sample (NIS) database from January 2003 to December 2018 was searched to identify all patients aged >18 years hospitalized with giant cell arteritis. Patients' baseline characteristics were summarized using descriptive statistics. Inferential statistics were done for categorical and continuous variables. Multivariate logistic regression, adjusting for patient and hospital-level cofounders was performed to find an association between race and outcomes of interest. RESULTS: Over the 15-year study period, a total of 8,352 patients (72.7% White, 14.5% Black or African American, 7.6% Hispanic, 2.2% Asian, 0.4% Alaska Native, and 2.6% under-represented populations) were hospitalized for GCA. The mean age at diagnosis was 73.6 ± 0.12 years. Women represented 71.9% of GCA patients and had a lower risk of mortality (OR 0.463, 95% CI: 0.235 - 0.912, p <0.05). Patients with GCA were hospitalized for an average of 4.64 days ± 0.04 days and 0.55% died. The mortality rate was lowest in Black or African American (0.1%) populations and highest among Alaska Native patients (8%). Mortality was 68% lower in those who had temporal artery biopsy (OR 0.32, 95% CI: 0.16-0.64, p <0.05). CONCLUSION: GCA disproportionally affected female patients, but mortality was higher in male patients. Alaska Native patients had the least number of hospitalizations but the highest in-hospital mortality rate. Black or African Americans had the lowest mortality rate.

Secondary pigmentary glaucoma following cosmetic laser treatment to alter iris colour.

Cosmetic alteration of iris colour with implants, along with its secondary complications, is already well described in the literature. However the use of cosmetic iris laser is relatively novel. We report on a rare case of bilateral secondary pigmentary glaucoma, in a young patient who underwent such a treatment to cause a change in iris pigmentation. Data on the safety of such procedures are lacking. Ophthalmic healthcare professionals should be aware of the potentially devastating consequences and encourage caution in patients seeking this novel treatment.

Focal Alveolar Hemorrhage Secondary to Hydralazine-Associated Antineutrophilic Cytoplasmic Antibody Vasculitis.

Hydralazine is rarely associated with antineutrophilic cytoplasmic antibody (ANCA) vasculitis. In the appropriate clinical scenario, such as in a patient with pulmonary, renal, or cutaneous manifestations, finding antibodies against nuclear and cytoplasmic neutrophil antigens may suggest drug-induced vasculitis after exposure to hydralazine. We present the case of an elderly man diagnosed with focal alveolar hemorrhage with elevated concentrations of anti-myeloperoxidase antibody, anti-proteinase-3 antibody, and antinuclear antibodies in the setting of prolonged hydralazine therapy. We observed a rapid clinical improvement with hydralazine discontinuation and systemic corticosteroids. We did not observe further disease activity while on mycophenolate mofetil six months later.

CT angiography for evaluation of cerebral vasospasm following acute subarachnoid haemorrhage.

INTRODUCTION: Cerebral vasospasm (CV) is one of the most dreaded complications in patients who survive acute subarachnoid haemorrhage (SAH), and conventional cerebral angiography (DSA) is the gold standard for its diagnosis. We evaluated CT angiography (CTA) as a non-invasive alternative for diagnosis of CV and assessed if CTA could have a role in choosing appropriate treatment. METHODS: Consecutive patients with SAH and suspected vasospasm were included when DSA was performed within 24 h from CTA. Two neuro-radiologists retrospectively analysed CTA and DSA studies independently. Assessment included presence of central and peripheral vasospasm and grading of severity of central CV. A treatment recommendation based on CTA was compared to actual treatment received. RESULTS: Final analysis included 34 patients. CTA was more accurate for diagnosis of central then for peripheral CV with high sensitivity (reader 1, 91%; reader 2, 92%), specificity (reader 1, 73%; reader 2, 90%), accuracy, positive predictive value and negative predictive value for central vasospasm. For grading the severity of CV CTA's sensitivity, specificity and accuracy were high for most central arteries. The reader's recommendation of angioplasty according to CTA was significantly predictive of actual receipt of angioplasty but overestimated actual receipt of triple H treatment. CONCLUSION: CTA is adequate for detecting central vasospasm in symptomatic SAH patients. A negative result should not prevent further investigation especially when evaluating arterial segments adjacent to metal artefacts from coils or clips. CTA is helpful in treatment decision making specifically regarding the need for balloon angioplasty.

Pulmonary Aspergillosis Complicated by Hemophagocytic Lymphohistiocytosis: A Case Report and Literature Review.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome involving excessive immune activation. It can be primary (familial) or secondary (triggered by infection, malignancy, or rheumatological disease). This is a case of a previously healthy 43-year-old African American woman who presented with fever and confusion. The patient was eventually diagnosed with pulmonary aspergillosis and responded well to antifungal therapy. She met the diagnostic criteria of HLH-2004 trial for hemophagocytic lymphohistiocytosis. She also fulfilled the 2019 classification criteria for systemic lupus erythematosus (SLE) without the classical signs and symptoms of SLE. HLH management includes supportive management, treatment of underlying condition, and immunosuppressive treatment. Etoposide and dexamethasone are commonly used treatments for HLH; however, underlying active infection can limit the treatment options. In our case, the patient was treated with steroids and hydroxychloroquine. Her condition gradually improved and she recovered without complications. Based on our literature review, we encountered six cases of HLH secondary to Aspergillosis with a mean age of approximately 47 years. The diagnosis of HLH is often delayed because of nonspecific presentation. Early identification and treatment are crucial to improve the survival rate.