Novel anionic surfactant-modified chlorhexidine and its potent antimicrobial properties.

Chlorhexidine dodecyl sulfate (CHX-DS) was synthesized and characterized via single-crystal X-ray diffraction (SC-XRD), 1H nuclear magnetic resonance (NMR) spectroscopy, 1H nuclear Overhauser effect spectroscopy (NOESY), and attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR). The solid-state structure, comprising a 1 : 2 stoichiometric ratio of chlorhexidine cations [C22H30Cl2N10]2+ to dodecyl sulfate anions [C12H25SO4]-, is the first report of chlorhexidine isolated with a surfactant. CHX-DS exhibits broad-spectrum antibacterial activity and demonstrates superior efficacy for reducing bacteria-generated volatile sulfur compounds (VSCs) as compared to chlorhexidine gluconate (CHG). The minimum inhibitory concentrations (MICs) of CHX-DS were 7.5, 2.5, 2.5, and 10 µM for S. enterica, E. coli, S. aureus, and S. mutans, respectively. Furthermore, MIC assays for E. coli and S. mutans demonstrate that CHX-DS and CHX exhibit a statistically significant efficacy enhancement in 2.5 µM treatment as compared to CHG. CHX-DS was incorporated into SBA-15, a mesoporous silica nanoparticle (MSN) framework, and its release was qualitatively measured via UV-vis in aqueous media, which suggests its potential as an advanced functional material for drug delivery applications.

Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Case Report With a Review of Management Options.

Angiotensin-converting enzyme inhibitors (ACEIs) are widely used for heart failure, renal failure, diabetic nephropathy, stroke, arterial hypertension, and a number of other cardiovascular or related conditions. ACEI-induced angioedema is a rare entity but can result in life-threatening emergencies. It mainly occurs in patients starting on ACEI as an antihypertensive. We present a case of lisinopril-induced angioedema in an African American patient managed in the emergency department. After appropriate evaluation, the patient was declared safe to be observed in the emergency department. Intubation was not performed. Early identification of angioedema is paramount, and emergency physicians should maintain airways or intubate such patients if indicated. There should be a high level of suspicion of angioedema in patients taking ACEIs if they present with symptoms of respiratory compromise.

The Rationale for Using Corticosteroids in COVID-19 Encephalopathy: Lessons From a Case Report With Evidence From Literature.

The coronavirus disease 2019 (COVID-19) virus primarily affects the pulmonary system, but neurological manifestations and complication of COVID-19 has been reported in abundance in the literature. We present a case of a middle-aged Caucasian male who was brought to the emergency department for altered mental status. His chief complaints were neurological rather than respiratory. A positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) nasal swab confirmed the diagnosis. Brain imaging showed mildly dilated ventricles with no other acute findings. As the patient did not require oxygen, he was treated with remdesivir alone without corticosteroids, which is also a precipitating factor of psychosis but, unfortunately, thickly used in practice. That led to remarkable results in full recovery without exposing the patient to steroid therapy. We strongly believe that remdesivir alone is sufficient in treating COVID-19-induced encephalopathy in a patient who does not require oxygen, and evidence supports this practice.

Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273) COVID-19 mRNA vaccines and hypersensitivity reactions.

The SARS-CoV-2 Virus (COVID-19) is responsible for over 239 million cases and 4.8 million deaths globally (Data source WHO COVID-19 Dashboard accessed on October 14, 2021). It continues to surge and ravage countries, leaving healthcare systems in constant struggle and uncertainty. A variety of vaccines were developed to combat the spread of the COVID-19 Virus. Reports of possible allergic reactions with COVID-19 vaccines are a significant cause of public concern, especially among those with a known history of a severe allergic reaction (e.g., anaphylaxis). Here we review articles relevant to COVID-19 vaccines and their excipients (especially PEG (Polyethylene glycol) and hypersensitivity reactions associated with COVID-19 vaccines (including clinical features, pathophysiology, special populations receiving COVID-19 vaccinations, potential diagnostic tests, and preventive measures that can be taken to minimize the risks of hypersensitivity reactions with COVID-19 vaccines).

An Overview of Systemic Lupus Erythematosus (SLE) Pathogenesis, Classification, and Management.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement. It is multifactorial and involves epigenetic, genetic, ecological, and environmental factors. Primarily it leads to activation of both innate and adaptive immunity, which consequently leads to autoreactive B cell activation by T cells and leads to immune complexes deposition in tissues leading to an autoimmune cascade that may be limited to the single organ or can cause a widespread systemic involvement. SLE is heterogeneous in presentation, with a broad spectrum of clinical manifestations ranging from clinically mild self-resolving symptoms to severe life-threatening organ involvement. Clinical and serological heterogeneity are critical features in SLE, posing a significant challenge in its diagnosis. Antinuclear antibodies (ANA) are the telltale serological marker in more than 95% of SLE patients. The improved set of European Alliance of Associations for Rheumatology (EULAR) classification enabled accurate diagnosis of SLE. The treatment focuses on remission, preventing organ damage, and improving the overall quality of life.

A Mysterious Case of Encephalitis: Diagnostic Challenge and Our Clinical Reasoning.

Acute psychotic symptoms in young patients are frequently attributed to toxic or infectious causes. After ruling out the most common causes, obtaining a firm diagnosis becomes challenging. In this case report, we present the case of a young woman who presented with acute psychosis after returning from a five-day vacation in Mexico. We treated this as a case of cerebral spinal fluid (CSF)-negative anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, as testing for CSF-NMDA receptor IgG antibodies was negative, and the absence of anti-NMDAR IgG antibodies does not rule out this autoimmune encephalitis. Moreover, IV methylprednisolone remarkably improved our patient's mental status and behavior. Anti-NMDAR encephalitis manifests itself in a variety of ways. As a result, providers must maintain a high level of suspicion based on their clinical assessment, as delays in labs or failure to diagnose early based on the clinical presentation can lead to delays in treatment with which this severe immune-mediated paraneoplastic condition can quickly escalate and have worse consequences. We describe our thought process behind our clinical judgment toward this atypical scenario to contribute to identifying this condition early on in the complex clinical presentation.

The roles of two extracellular loops in proton sensing and permeation in human Otop1 proton channel.

Otopetrin (Otop) proteins were recently found to function as proton channels, with Otop1 revealed to be the sour taste receptor in mammals. Otop proteins contain twelve transmembrane segments (S1-S12) which are divided into structurally similar N and C domains. The mechanisms by which Otop channels sense extracellular protons to initiate gating and conduct protons once the channels are activated remains largely elusive. Here we show that two extracellular loops are playing key roles in human Otop1 channel function. We find that residue H229 in the S5-S6 loop is critical for proton sensing of Otop1. Further, our data reveal that the S11-12 loop is structurally and functionally essential for the Otop1 channel and that residue D570 in this loop regulates proton permeation into the pore formed by the C domain. This study sheds light on the molecular mechanism behind the structure and function of this newly identified ion channel family.

Negative pressure pulmonary oedema due to rigors and chills associated with liver abscess.

A 61-year-old male presented with progressive generalized weakness, myalgia, diaphoresis, fever, episodic chills and rigors that had started 4 days previously. Chest x-ray (CXR) showed overlying curvilinear radio-opacities. Abdominal computed tomography revealed liver and bilateral adrenal lesions. Empiric 7-day intravenous Piperacillin / Tazobactam (Zosyn) was initiated, and he was admitted for sepsis. After an episode of rigors on Day 2, he developed acute hypoxic respiratory failure with inspiratory stridor. CXR revealed new, bilateral airspace disease. Racemic Epinephrine, Solumedrol, Ketorolac (Toradol) and Diphenhydramine were given, and he was transferred to the intensive care unit with presumptive diagnosis of foreign body aspiration or allergic reaction. With each subsequent episode of rigor and chills, he continued developing hypoxic respiratory failure with stridor and an incremental increase in pulmonary oedema on imaging. Pulmonologist concluded it likely secondary to negative pressure pulmonary oedema caused by transient laryngeal dyskinesia induced by the increased work of breathing associated with rigors. Symptoms resolved after the complete course of antibiotics along with supportive therapy.

The ion channel function of polycystin-1 in the polycystin-1/polycystin-2 complex.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2 gene, encoding the polycystic kidney disease protein polycystin-1 and the transient receptor potential channel polycystin-2 (also known as TRPP2), respectively. Polycystin-1 and polycystin-2 form a receptor-ion channel complex located in primary cilia. The function of this complex, especially the role of polycystin-1, is largely unknown due to the lack of a reliable functional assay. In this study, we dissect the role of polycystin-1 by directly recording currents mediated by a gain-of-function (GOF) polycystin-1/polycystin-2 channel. Our data show that this channel has distinct properties from that of the homomeric polycystin-2 channel. The polycystin-1 subunit directly contributes to the channel pore, and its eleven transmembrane domains are sufficient for its channel function. We also show that the cleavage of polycystin-1 at the N-terminal G protein-coupled receptor proteolysis site is not required for the activity of the GOF polycystin-1/polycystin-2 channel. These results demonstrate the ion channel function of polycystin-1 in the polycystin-1/polycystin-2 complex, enriching our understanding of this channel and its role in ADPKD.

Cross Sectional Study and Risk Factors Analysis of Francisella tularensis in Soil Samples in Punjab Province of Pakistan.

Tularemia is an endemic zoonotic disease in many parts of the world including Asia. A cross-sectional study was conducted to determine genome-based prevalence of Francisella tularensis (Ft) in soil, assess an association between its occurrence in soil and likely predictors i.e., macro and micro-nutrients and several categorical variables, and determine seroconversion in small and large ruminants. The study included a total of 2,280 soil samples representing 456 villages in eight districts of the Punjab Province of Pakistan followed by an analysis of serum antibodies in 707 ruminants. The genome of Ft was detected in 3.25% (n = 74, 95% CI: 2.60-4.06) of soil samples. Soluble salts (OR: 1.276, 95% CI: 1.043-1.562, p = 0.015), Ni (OR: 2.910, 95%CI: 0.795-10.644, p = 0.106), Mn (OR:0.733, 95% CI:0.565-0.951, p = 0.019), Zn (OR: 4.922, 95% CI:0.929-26.064, p = 0.061) and nutrients clustered together as PC-1 (OR: 4.76, 95% CI: 2.37-9.54, p = 0.000) and PC-3 (OR: 0.357, 95% CI: 0.640, p = 0.001) were found to have a positive association for the presence of Ft in soil. The odds of occurrence of Ft DNA in soil were higher at locations close to a water source, including canals, streams or drains, [χ2 = 6.7, OR = 1.19, 95% CI:1.05-3.09, p = 0.004] as well as places where animals were present [χ2 = 4.09, OR = 2.06, 95% CI: 1.05-4.05, p = 0.02]. The seroconversion was detected in 6.22% (n = 44, 95% CI: 4.67-8.25) of domestic animals. An occurrence of Ft over a wide geographical region indicates its expansion to enzootic range, and demonstrates the need for further investigation among potential disease reservoirs and at-risk populations, such as farmers and veterinarians.

Assessment of Mediastinal Lymph Node Size in Pneumococcal Pneumonia with Bacteremia.

INTRODUCTION: The significance of mediastinal lymphadenopathy in bacterial pneumonia is unclear. METHODS: We performed a retrospective analysis of mediastinal lymph node size determined by chest CT in patients with bacteremic pneumococcal pneumonia. All patients who had positive blood cultures for streptococcus pneumonia over an 11-year period and had a chest CT scan (index CT) within 2 weeks of the positive blood culture were included in the study. Two thoracic radiologists and one pulmonologist independently examined the index CT plus any chest CT scans performed prior (pre-CT) or after (post-CT) the bacteremic episode. RESULTS: The study cohort of 49 patients was 57% male, 65% White, with mean age of 53 (SD = 20) years. Mediastinal lymphadenopathy was detected in 25/49 (51%) of the cases. The mean size of the largest mediastinal lymph node in short axis was 0.99 (SD = 0.71), ranging from 0.0 to 2.05 cm. There was no correlation noted between the number of lobes involved with pneumonia, and the size of the largest mediastinal lymph node (p = 0.33) or the number of pathologically enlarged mediastinal lymph nodes (p = 0.08). There was a statistically significant increase in the mean size of the largest lymph node between the pre-CT and index-CT group (p = 0.02), and decrease between the index-CT group and the post-CT (p = 0.03). CONCLUSION: Pneumococcal pneumonia with bacteremia is associated with mild mediastinal lymph node enlargement. The presence of marked mediastinal lymphadenopathy (short axis LN size > 2 cm) should not be assumed from pneumococcal pneumonia.

Seroprevalence and risk factors of glanders in working equines - Findings of a cross-sectional study in Punjab province of Pakistan.

Glanders is an infectious and contagious bacterial disease of equines. A little is known about its seroprevalence and risk factors in working equines in countries where the disease is endemic. Also, there are no reports on prevalence of the disease in areas where there is a prior evidence of Burkholderia (B.) mallei detection in soil. A cross-sectional study was conducted in selected districts (n=09) of Punjab province of Pakistan during 2014-2015. A total of 1008 serum samples were screened for detection of antibodies to B. mallei with complement fixation test followed by western blot. The overall seroprevalence was found to be 3.17% (95% CI: 2.25-4.44). The seropositivity was significantly higher from the sampling sites where B. mallei was detected in soil [OR: 10.66 (95% CI: 4.42-31.66), p=0.00]. Other risk factors significantly associated with animal seropositivity were: age group [OR: 1.78 (95% CI: 4.58-15.56), p=0.00], location in urban area [OR: 2.99 (95% CI: 1.46-6.51), p=0.00],body condition [OR: 3.47 (95% CI: 1.64-7.99), p=0.00], presence of farcy lesion[OR: 7.71 (95% CI: 3.47-19.50), p=0.00], proximity to water bodies [OR: 7.71 (95% CI: 3.47-19.50), p=0.00]; domestic animal population [OR: 3.20 (95% CI: 1.24-10.87), p=0.03] and number of households in sampling area [OR: 4.18 (95%CI: 1.82-11.30), p=0.00]. The study provides an estimate of prevalence of glanders and a potential link between animal seropositivity and presence of B. mallei in soil. The risk factors identified in this study can be used in surveillance and disease awareness. The high prevalence of disease in draught horses and contact of infected animals with their care-takers in developing countries signify need to initiate progressive control of the disease using one health approach.

The role of serum amyloid A staining of granulomatous tissues for the diagnosis of sarcoidosis.

BACKGROUND: Previous studies demonstrated that SAA staining of sarcoidosis granulomas was qualitatively and quantitatively different from other granulomatous diseases. These data suggest that positive SAA staining of granulomatous tissue may have adequate specificity to establish a diagnosis of sarcoidosis. Our objective was to determine the diagnostic specificity of SAA staining for sarcoidosis relative to other granulomatous disorders. METHODS: Pathological specimens demonstrating granulomatous inflammation were retrospectively identified at one institution, plus 4 specimens were obtained from New York City firefighters with biopsy-confirmed World Trade Center "sarcoidosis-like" pulmonary disease. Specimens were analyzed if specific diagnoses related to the granulomatous inflammation were confirmed through medical record review. SAA staining was performed using previously developed methods. Two pathologists, blinded to each other and the diagnoses, determined if the stained material was SAA positive or negative. Discordant results were adjudicated by the two pathologists. MEASUREMENTS AND MAIN RESULTS: 106 specimens were analyzed from 100 patients, with 36 biopsies (34%) from sarcoidosis tissues and 70 (66%) from other granulomatous disorders. The Cohen Kappa correlation between the two pathologists for SAA staining positivity was excellent (0.85, 0.73-0.98). The overall specificity of SAA staining for the diagnosis of sarcoidosis was 84% (59/70). The sensitivity was 44% (16/36). CONCLUSIONS: Although SAA staining of various granulomatous tissues was fairly specific for the diagnosis of sarcoidosis, the specificity was inadequate for SAA staining to be used as a diagnostic test for sarcoidosis in isolation. These data suggest that SAA production may not be a universal mechanism in the development of sarcoidosis.

Proteinuria in sarcoidosis: Prevalence and risk factors in a consecutive outpatient cohort.

Introduction: While sarcoidosis has been recognized as a potential cause of proteinuria, no study has systematically evaluated the prevalence and risk factors for proteinuria in sarcoid patients. Methods: Consecutive sarcoid patients followed in a university clinic were identified prospectively. All patients with spot urine protein-to-creatinine ratio (UPCR) between 11-2012 and 07-2015 were included in the analysis. Proteinuria was defined as a spot UPCR equal to or exceeding 0.3 mg/mg. The primary goal of the study was to determine the prevalence of proteinuria in this sarcoidosis cohort. Results: Our study cohort consisted of 190 sarcoidosis patients (65% female, 82% white, mean age of 53 years (range 24-88)). Proteinuria was present in 14/190 (7%) of this cohort. Only5/190 patients (2.5%) had proteinuria who did not have a risk factor for proteinuria. Estimating the 24-hour urine protein excretion by extrapolating from the spot UPCR, proteinuria was moderate in amount (mean 1.60, range 0.32-5.06 mg/mg). Proteinuric patients received a lower mean daily dose of corticosteroids compared to those without proteinuria (0 mg vs 4.7 mg of prednisone); however, this difference did not reach statistical significance (p = 0.20). Conclusion: Our study found proteinuria in 7% of the 190 sarcoid patients. More than half of the patients with proteinuria had a known risk factor for proteinuria other than sarcoidosis. Proteinuria is uncommon in sarcoidosis, and, when it occurs, it should not be assumed that sarcoidosis is the cause without investigating alternative causes of proteinuria. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 142-148).

Prospective study of avian influenza H9 infection in commercial poultry farms of Punjab Province and Islamabad Capital Territory, Pakistan.

A prospective study was conducted from November 2013 to February 2014 to estimate the spatial clustering; cumulative incidence and risk factors associated with avian influenza (AI) subtype H9 infection on commercial poultry farms of Pakistan. A total of 400 farms were enrolled and followed during the study period. Among these, 109 farms submitted samples suspected for AI to the laboratory, and only 47 farms were confirmed positive by hemagglutinin inhibition (HI) test. Data was collected from these 109 farms about their demography, management, and biosecurity practices. The cumulative incidence of H9N2 was 11.75 % (95 % confidence interval (CI) 8.76-15.23). The highest number of cases (40.42 %) was reported in January. One most likely cluster (p = 0.009, radius = 4.61 km) occurred in the Kasur district. Multivariable logistic regression analyses showed that the presence of wild birds on the farms (odds ratio (OR) = 16.18; 95 % CI 3.94-66.45) was independently associated with H9N2 infection. Cleaning of cages before delivery on farm (OR = 0.16; 95 % CI = 0.06-0.47), presence of a footbath at the entrance of farm (OR = 0.24; 95 % CI 0.08-0.79), and changing of gloves (OR = 0.33; 95 % CI 0.11-0.99) were protective factors against H9N2 infection. Reducing the exposure to risk factors and adapting biosecurity measures may reduce the risk of AI H9N2 infection on commercial poultry farms in Pakistan.

Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features.

Mutations that cause neurological phenotypes are highly informative with regard to mechanisms governing human brain function and disease. We report autosomal recessive mutations in the enzyme glutamate pyruvate transaminase 2 (GPT2) in large kindreds initially ascertained for intellectual and developmental disability (IDD). GPT2 [also known as alanine transaminase 2 (ALT2)] is one of two related transaminases that catalyze the reversible addition of an amino group from glutamate to pyruvate, yielding alanine and α-ketoglutarate. In addition to IDD, all affected individuals show postnatal microcephaly and ∼80% of those followed over time show progressive motor symptoms, a spastic paraplegia. Homozygous nonsense p.Arg404* and missense p.Pro272Leu mutations are shown biochemically to be loss of function. The GPT2 gene demonstrates increasing expression in brain in the early postnatal period, and GPT2 protein localizes to mitochondria. Akin to the human phenotype, Gpt2-null mice exhibit reduced brain growth. Through metabolomics and direct isotope tracing experiments, we find a number of metabolic abnormalities associated with loss of Gpt2. These include defects in amino acid metabolism such as low alanine levels and elevated essential amino acids. Also, we find defects in anaplerosis, the metabolic process involved in replenishing TCA cycle intermediates. Finally, mutant brains demonstrate misregulated metabolites in pathways implicated in neuroprotective mechanisms previously associated with neurodegenerative disorders. Overall, our data reveal an important role for the GPT2 enzyme in mitochondrial metabolism with relevance to developmental as well as potentially to neurodegenerative mechanisms.

Effect of SSRIs and SNRIs on Nocturnal Urinary Frequency.

BACKGROUND: Existing data suggest that selective serotonin uptake inhibitors (SSRIs) may have an impact on urinary frequency. OBJECTIVE: To evaluate the impact of SSRIs and selective noradrenaline reuptake inhibitors (SNRIs) on nocturnal urinary frequency. METHODS: This was a retrospective study comparing nocturnal urinary frequency in individuals on SSRI or SNRI therapy versus no therapy during nocturnal polysomnography in a 14-month period at a sleep center. RESULTS: A total of 316 individuals were studied: 94 in the SSRI/SNRI group and 222 controls. No statistically significant difference was found in nocturnal urinary frequency between those on SSRI/SNRI therapy and the control group (0.40 vs 0.34 bathroom visits/night, P = 0.40). The degree of urinary frequency was higher in sertraline users (0.61 bathroom visits/night) compared with duloxetine users (0.18 visits/night, 2-tailed P = 0.04). A post hoc analysis suggested that the difference between these 2 agents is a class effect (SSRIs vs SNRIs, 2-tailed P = 0.03). The sample size did not allow conclusive comparison of either the SSRI or the SNRI group with the control group. CONCLUSION: SSRI/SNRI agents as a combined group do not appear to have a significant impact on nocturnal urinary frequency. The SSRIs and SNRIs may have an opposite effect on nocturnal frequency.

The effect of corticosteroids on quality of life in a sarcoidosis clinic: the results of a propensity analysis.

BACKGROUND: Both sarcoidosis and its treatment may worsen health related quality of life (HRQoL). We performed a propensity analysis of sarcoidosis-specific HRQoL patient reported outcome measures (PRO) to disentangle the effects of sarcoidosis and corticosteroid therapy on HRQoL in sarcoidosis outpatients. METHODS: Consecutive outpatient sarcoidosis patients were administered modules from two sarcoidosis-specific HRQoL PROs: the Sarcoidosis Health Questionnaire (SHQ) and the Sarcoidosis Assessment Tool (SAT). Patients were divided into those that received ≤500 mg of prednisone (PRED-LOW) versus >500 mg of prednisone (PRED-HIGH) over the previous year. SAT and SHQ scores were initially compared in the two corticosteroid groups. Then a multivariate analysis was performed using a propensity score analysis adjusted for race, age, gender and the severity of illness. RESULTS: In the unadjusted analysis, the PRED-HIGH group demonstrated the following worse HRQoL scores compared to the LOW-PRED group: SHQ Daily (p = 0.02), SAT satisfaction (p = 0.03), SAT daily activities (p = 0.03). In the propensity analysis, the following domains demonstrated worse HRQoL in the PRED-HIGH group than the PRED-LOW group: SAT fatigue (p < 0.0001), SAT daily activities (p = 0.03), SAT satisfaction (p = 0.03). All these differences exceeded the established minimum important difference for these SAT domains. The SHQ Physical score appeared to demonstrate a borderline improved HRQoL in the PRED-HIGH versus the PRED-LOW group (p = 0.05).). In a post-hoc exploratory analysis, the presence of cardiac sarcoidosis may have explained the quality of life differences between the two corticosteroid groups. CONCLUSIONS: Our cohort of sarcoidosis clinic patients who received ≤500 mg of prednisone in the previous year had an improved HRQoL compared to patients receiving >500 mg on the basis of two sarcoidosis-specific PROs after adjusting for severity of illness. These data support the need to measure HRQoL in sarcoidosis trials, and suggest that the search should continue for effective alternative medications to corticosteroids.