Tracking KP.2 SARS-CoV-2 Variant in India and the Clinical Profile of KP.2 Cases in Maharashtra, India.

BACKGROUND:  Following the emergence of the JN.1 SARS-CoV-2 variant, variants with key mutations in the spike protein, such as L455F, F456L, and R346T, were identified. In early January 2024, the KP.2 (JN.1.11.1.2) variant was first identified in clinical samples. Its increasing global prevalence has raised concerns over its transmission and clinical impact. The study investigates KP.2*'s (*indicates KP.2 and all its sub-lineages) spread and clinical severity in Maharashtra. METHODS:  This study involved 5,173 Indian SARS-CoV-2 whole genome sequences with collection dates between November 1, 2023 and June 24, 2024. Lineage analysis of sequences was performed using Nextclade software (version 3.8.0). Telephonic interviews were conducted to confirm the demographic details and obtain clinical information on the KP.2* cases. The obtained data were recorded and analyzed using Microsoft® Excel (Microsoft Corporation, Redmond, WA). RESULTS:  Among the 5,173 sequences analyzed, JN.1* appeared as the predominant lineage (65.96%, 3412/5173), followed by KP.2* (7.83%, 405/5173) and KP.1* (3.27%, 169/5173). In India, KP.2* was first detected on December 2, 2023, in Odisha. The majority of KP.2* sequences were from Maharashtra (248/405, 61.23%), followed by West Bengal (38/405, 9.38%), Gujarat (27/405, 6.67%), and Rajasthan (24/405, 5.93%). Maharashtra reported its first KP.2* sequences on January 24, 2024. The clinical study included 160 cases of the KP.2* variant from Maharashtra. Of these, 95.63% (153/160) presented with mild symptoms, such as fever (108/160, 67.50%), cold (87/160, 54.38%), cough (80/160, 50%), sore throat (44/160, 27.5%), body ache (43/160, 26.88%), and fatigue (42/160, 26.25%). About 33.13% (53/160) of the cases required institutional quarantine or hospitalization, with the rest managed at home. Among those hospitalized, 50.94% (27/53) received conservative treatment, while 49.06% (26/53) needed supplemental oxygen, steroids, or antiviral therapy. Regarding the vaccination status, 89.38% (143/160) of the cases had received at least one dose of the COVID-19 vaccine, whereas 10% (16/160) were unvaccinated, with the majority of the unvaccinated being children aged zero to nine years (7/16, 43.75%). The overall recovery rate for KP.2* cases was 99.38% (159/160), with only 0.62% (1/160) succumbing to the disease. CONCLUSION:  The KP.2 variant has become the dominant SARS-CoV-2 variant in India and Maharashtra. Despite the affected individuals experiencing mild symptoms, studies have shown lower neutralization titers and high infectivity due to FLiRT mutations, suggesting KP.2's potential rise to global dominance.

Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Homeless Shelters in Chicago, Illinois-March-May, 2020.

BACKGROUND: People experiencing homelessness are at increased risk of coronavirus disease 2019 (COVID-19), but little is known about specific risk factors for infection within homeless shelters. METHODS: We performed widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing and collected risk factor information at all homeless shelters in Chicago with at least 1 reported case of COVID-19 (n = 21). Multivariable, mixed-effects log-binomial models were built to estimate adjusted prevalence ratios (aPRs) for SARS-CoV-2 infection for both individual- and facility-level risk factors. RESULTS: During March 1 to May 1, 2020, 1717 shelter residents and staff were tested for SARS-CoV-2; 472 (27%) persons tested positive. Prevalence of infection was higher for residents (431 of 1435, 30%) than for staff (41 of 282, 15%) (prevalence ratio = 2.52; 95% confidence interval [CI], 1.78-3.58). The majority of residents with SARS-CoV-2 infection (293 of 406 with available information about symptoms, 72%) reported no symptoms at the time of specimen collection or within the following 2 weeks. Among residents, sharing a room with a large number of people was associated with increased likelihood of infection (aPR for sharing with >20 people compared with single rooms = 1.76; 95% CI, 1.11-2.80), and current smoking was associated with reduced likelihood of infection (aPR = 0.71; 95% CI, 0.60-0.85). At the facility level, a higher proportion of residents leaving and returning each day was associated with increased prevalence (aPR = 1.08; 95% CI, 1.01-1.16), whereas an increase in the number of private bathrooms was associated with reduced prevalence (aPR for 1 additional private bathroom per 100 people = 0.92; 95% CI, 0.87-0.98). CONCLUSIONS: We identified a high prevalence of SARS-CoV-2 infections in homeless shelters. Reducing the number of residents sharing dormitories might reduce the likelihood of SARS-CoV-2 infection. When community transmission is high, limiting movement of persons experiencing homelessness into and out of shelters might also be beneficial.

Improving Adherence to Practice Guidelines for Anticoagulation in Patients Receiving Neuraxial Anesthesia Using an Electronic Order Entry Alert System.

OBJECTIVES: Epidural analgesia is frequently used to alleviate postoperative pain. Though rare, epidural hematoma continues to be a feared complication of neuraxial analgesia. The risk of epidural hematoma is likely increased when certain regimens are used for prophylaxis/treatment of venous thromboembolism. To help decrease the risk, we developed an alert in our electronic medical record to assist providers with adherence to published guidelines addressing neuraxial analgesia and anticoagulation. METHODS: Patient data were collected retrospectively 3 months before and 3 months after the initiation of the computerized alert to assess the effectiveness of the alert. Patients were included if they had a procedure code associated with epidural analgesia. Pregnant patients and children were excluded. Type and frequency of antithrombotic medications were recorded for comparison to published practice guidelines. RESULTS: Using Poisson regression to describe the data, patients with epidurals after the best practice alert observed a 61% decrease in the expected number of days of exposure to inappropriate doses of anticoagulation versus patients treated before implementation of the alert. CONCLUSION: Unapproved antithrombotic administration was significantly reduced after initiation of the alert system. This simple electronic alert was found to have a protective effect for patients receiving both anticoagulation and epidural analgesia.

Fenofibrate: A Nonlithogenic Means of Recurrent Drug-Induced Pancreatitis.

Medications account for a small portion of the various etiologies of acute pancreatitis. Prompt identification of drugs as the inciting factor decreases disease recurrence and unnecessary invasive diagnostic intervention. This case is a report of fenofibrate-induced acute pancreatitis including a disease recurrence with continuation of fenofibrate which subsequently resolved after drug discontinuation. The patient underwent invasive diagnostic evaluation including endoscopic ultrasound with fine needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP). Based on exclusion of other disease etiologies and a positive drug rechallenge, fenofibrate fits as a class 1A medication in the classification of drug-induced pancreatitis.

A High-Throughput Mass-Spectrometry-Based Assay for Identifying the Biochemical Functions of Putative Glycosidases.

The most commonly employed glycosidase assays rely on bulky ultraviolet or fluorescent tags at the anomeric position in potential carbohydrate substrates, thereby limiting the utility of these assays for broad substrate characterization. Here we report a qualitative mass spectrometry-based glycosidase assay amenable to high-throughput screening for the identification of the biochemical functions of putative glycosidases. The assay utilizes a library of methyl glycosides and is demonstrated on a high-throughput robotic liquid handling system for enzyme substrate screening. Identification of glycosidase biochemical function is achieved through the observation of an appropriate decrease in mass between a potential sugar substrate and its corresponding product by electrospray ionization mass spectrometry (ESI-MS). In addition to screening known glycosidases, the assay was demonstrated to characterize the biochemical function and enzyme substrate competency of the recombinantly expressed product of a putative glycosidase gene from the thermophilic bacterium Thermus thermophilus.

Analysis of redox and apoptotic effects of anthracyclines to delineate a cardioprotective strategy.

PURPOSE: Cardiotoxic side effects of anthracyclines limit their use as effective chemotherapeutics. One mechanistic model of anthracycline-induced cardiotoxicity is attributed to the generation of intracellular reactive oxygen species (ROS). However, this theory has been questioned because several cardioprotective strategies have included the use of antioxidants without significant clinical benefit. We sought to determine whether measurement of intracellular reactive oxygen species after anthracycline exposure in vivo and in vitro could provide a means for designing more effective antioxidant-based cardioprotective schemes. METHODS: Intracellular levels of ROS were assessed in peripheral blood mononuclear cells from leukemia bearing mice exposed to anthracyclines and in patients receiving anthracyclines. Comparison of cell death induction and ROS levels were also conducted in vitro in cardiomyocyte and leukemia lines. ROS blockade using antioxidants was conducted, and effects on cell death were assessed. RESULTS: Elevated ROS in blood of mice and representative patient samples correlated with cardiomyocyte necrosis and decreased ejection fraction. In vitro, comparison of the cytotoxic effects of anthracyclines in acute leukemia cells and in cardiomyocytes revealed distinct kinetics of cell death induction and dependence upon oxidative stress. Although apoptotic cell death was observed in both acute leukemia cells and cardiomyocytes, the antioxidant N-acetylcysteine protected cardiomyocytes but not acute leukemia cells from anthracycline cytotoxicity. CONCLUSIONS: Our findings point toward revisiting the use of NAC as a cardioprotective agent since it does not appear to interfere with the cytotoxic action of anthracyclines. NAC has been evaluated clinically for cardioprotective activity but future trials must ensure that adequate dose, scheduling and incorporation of markers of oxidative stress are included.

Exploring allosteric activation of LigAB from Sphingobium sp. strain SYK-6 through kinetics, mutagenesis and computational studies.

The protocatechuate 4,5-dioxygenase (LigAB) from Sphingobium sp. strain SYK-6 is the defining member of the Type II extradiol dioxygenase superfamily (a.k.a. PCA Dioxygenase Superfamily or PCADSF) and plays a key aromatic ring-opening role in the metabolism of several lignin derived aromatic compounds. In our search for alternate substrates and inhibitors of LigAB, we discovered allosteric rate enhancement in the presence of non-substrate protocatechuate-like aldehydes such as vanillin. LigAB has the broadest substrate utilization profile of all protocatechuate (PCA) 4,5-dioxygenase described in the literature, however, the rate enhancement is only observed with PCA, with vanillin increasing kcat for LigAB by 36%. Computational docking has identified a potential site of allosteric binding near the entrance to the active site. Examination of a multiple sequence alignment reveals that many of the residues contributing to this newly identified allosteric pocket are highly conserved within the LigB family of the PCADSF. Point mutants of Phe103α and Ala18ß, two residues located in the putative allosteric pocket, display altered rate enhancement as compared to LigAB-WT, providing support for the computationally identified allosteric binding site. Further investigation of this binding site may provide insight into the mechanism of this never before observed allosteric activation in extradiol dioxygenases.

MotherSafe: review of three years of counselling by an Australian Teratology Information Service.

BACKGROUND: MotherSafe was established in January 2000 at the Royal Hospital for Women as Australia's first 'purpose-built' Teratogen Information Service and since then has received over 75,000 calls regarding exposures during pregnancy and lactation. AIM: To describe the patterns of use of MotherSafe over a three-year period. METHODS: Retrospective descriptive epidemiological study using data from the database established at MotherSafe. Records from all the calls logged at MotherSafe between January 2005 and December 2007 were analysed to determine total number of calls, demographic characteristics of callers, including age, caller category and postcode, reason for call, source of referral and type of exposure. RESULTS: A total of 47,138 calls were recorded to the MotherSafe service from January 2005 to December 2007. The majority of calls were regarding exposures in pregnancy (55%) and breast-feeding (38%). Average age of patients was 32.3 years. Of the calls made, 81.9% (38,485 of 46,968) were by consumers (the pregnant or lactating woman herself or a relative). The most common primary exposure categories were: over-the-counter medications (11.3%), psychotropic medication (9.0%), herbal or vitamin products (8.2%), antibiotics (7.0%), gastrointestinal medications (6.8%) and topical products (6.6%). Forty per cent of callers enquired about multiple exposures. CONCLUSIONS: The utilisation of MotherSafe by consumers and general practitioners continues to increase, reflecting the strong demand for a teratogen counselling service that provides high-quality, evidence-based information on exposures during pregnancy and lactation.