KPC-2-producing Enterobacterales from ready-to-eat food to hospitalized patients.

Foodstuffs are a well-documented source of multidrug-resistant bacteria, and hospitalized patients are usually susceptible to hospital infections owing to their immune status. Therefore, this study aimed to investigate the presence of beta-lactamase-producing Enterobacterales in ready-to-eat foods consumed by hospitalized patients. For this purpose, 51 vegetable and meat samples were collected over 2 months and analyzed. Enterobacterales isolates were identified and subjected to antimicrobial susceptibility testing, followed by beta-lactamase gene screening, pH tolerance assays, and whole-genome sequencing (WGS). Isolates harboring genes encoding extended-spectrum beta-lactamases, cephalosporinases, or carbapenemases were detected, and all isolates tolerated pH levels similar to those in the human gastrointestinal tract. The blaKPC-2 carriers were characterized by WGS and lineages closely related to those causing human infections were identified. These results showed that dietary intake is an alternative route for the transmission of antimicrobial-resistant bacteria, which must be considered when designing effective strategies for infection control.

Brain-Derived Neurotrophic Factor as a Potential Mediator of the Beneficial Effects of Myo-Inositol Supplementation during Suckling in the Offspring of Gestational-Calorie-Restricted Rats.

This study aims to investigate the potential mechanisms underlying the protective effects of myo-inositol (MI) supplementation during suckling against the detrimental effects of fetal energy restriction described in animal studies, particularly focusing on the potential connections with BDNF signaling. Oral physiological doses of MI or the vehicle were given daily to the offspring of control (CON) and 25%-calorie-restricted (CR) pregnant rats during suckling. The animals were weaned and then fed a standard diet until 5 months of age, when the diet was switched to a Western diet until 7 months of age. At 25 days and 7 months of age, the plasma BDNF levels and mRNA expression were analyzed in the hypothalamus and three adipose tissue depots. MI supplementation, especially in the context of gestational calorie restriction, promoted BDNF secretion and signaling at a juvenile age and in adulthood, which was more evident in the male offspring of the CR dams than in females. Moreover, the CR animals supplemented with MI exhibited a stimulated anorexigenic signaling pathway in the hypothalamus, along with improved peripheral glucose management and enhanced browning capacity. These findings suggest a novel connection between MI supplementation during suckling, BDNF signaling, and metabolic programming, providing insights into the mechanisms underlying the beneficial effects of MI during lactation.

ROS-Responsive 4D Printable Acrylic Thioether-Based Hydrogels for Smart Drug Release.

Reactive oxygen species (ROS) play a key role in several biological functions like regulating cell survival and signaling; however, their effect can range from beneficial to nondesirable oxidative stress when they are overproduced causing inflammation or cancer diseases. Thus, the design of tailor-made ROS-responsive polymers offers the possibility of engineering hydrogels for target therapies. In this work, we developed thioether-based ROS-responsive difunctional monomers from ethylene glycol/thioether acrylate (EGnSA) with different lengths of the EGn chain (n = 1, 2, 3) by the thiol-Michael addition click reaction. The presence of acrylate groups allowed their photopolymerization by UV light, while the thioether groups conferred ROS-responsive properties. As a result, smart PEGnSA hydrogels were obtained, which could be processed by four-dimensional (4D) printing. The mechanical properties of the hydrogels were determined by rheology, pointing out a decrease of the elastic modulus (G') with the length of the EG segment. To enhance the stability of the hydrogels after swelling, the EGnSA monomers were copolymerized with a polar monomer, 2-hydroxyethyl acrylate (HEA), leading to P[(EGnSA)x-co-HEAy] with improved compatibility in aqueous media, making it a less brittle material. Swelling properties of the hydrogels increased in the presence of hydrogen peroxide, a kind of ROS, reaching values of ≈130% for P[(EG3SA)7-co-HEA93] which confirms the stimuli-responsive properties. Then, the P[(EG3SA)x-co-HEAy] hydrogels were employed as matrixes for the encapsulation of a chemotherapeutic drug, 5-fluorouracil (5FU), which showed sustained release over time modulated by the presence of H2O2. Finally, the effect of the 5-FU release from P[(EG3SA)x-co-HEAy] hydrogels was tested in vitro with melanoma cancer cells B16F10, pointing out B16F10 growth inhibition values in the range of 40-60% modulated by the EG3SA percentage and the presence or absence of ROS agents, thus confirming their excellent ROS-responsive properties for the treatment of localized pathologies.

The differential role of SSa/SSb and Ro52 antibodies in defining clinical phenotypes in idiopathic inflammatory myopathies.

OBJECTIVE: In idiopathic inflammatory myopathies, anti-SSa/SSb and anti-Ro52 are associated with interstitial lung disease (ILD), yet few studies have compared their prognostic utility. Our study analyzes clinical phenotypes associated with anti-SSa/SSb and anti-Ro52 positivity in IIM and their association with ILD. METHODS: We performed a retrospective analysis of IIM patients >18-years-old, seen at Northwell Myositis Center 2007- 2018 who met 2017 EULAR/ACR criteria with available anti-SSa/SSb data. Patients who were anti-SSa/SSb(-) and anti-Ro52(+) were excluded from anti-SSa/SSb subgroup analysis but included in Ro52 subgroup analysis. Organ manifestations, pulmonary function tests (PFTs) and comorbidities were recorded. Statistical analyses included Chi-square, Fisher's Exact, Wilcoxon Rank Sum, McNemar's test. RESULTS: Of 94 patients included in the final analysis, 35% (33/94) were anti-SSa/SSb positive (+). Of 60 patients with anti-Ro52 data, 42% (25/60) were (+). ILD was more common in anti-SSa/SSb (+) versus anti-SSa/SSb negative patients and anti-Ro52(+) versus anti-Ro52 negative patients (58% vs 25%; p = 0.003 and 64% vs.26%; p = 0,004 respectively). Anti-SSa/SSb (+) was not associated with increased ILD severity based on PFTs. Anti-Ro52(+) group had lower DLCO than anti-Ro52(-) (47% vs 68%; p = 0.003). Anti-SSa/SSb positivity did not confer a difference in the frequency of other manifestations. Elevated rates of venous thromboembolism (VTE) (10%-12%) and osteoporosis (13-17%) were observed independent of anti-SSa/SSb or anti-Ro52 status. CONCLUSION: In IIM anti-SSa/SSb or anti-Ro52 positivity is associated with higher ILD rate. Both assays are useful to confer ILD risk, but anti-Ro52 is more predictive of severe ILD. High frequencies of osteoporosis and VTE were observed in all subgroups.

Racial Disparities in Diagnosis and Treatment of Patients With Dermatomyositis of Different Skin Tones.

BACKGROUND: Delays in the diagnosis and treatment of dermatological conditions in minorities are a well-documented health disparity. We aimed to determine if there was a delay in detection and treatment initiation for dermatomyositis (DM) and amyopathic dermatomyositis (ADM) in patients of different skin tones. METHODS: Patients from Montefiore Medical Center who met the criteria for DM and ADM were included in this cohort study. Records were reviewed for date of first documented rash, creatine kinase levels, muscle weakness complaints, and date of first steroid or disease-modifying antirheumatic drug initiation. The median number of days between rash documentation and therapy initiation was compared for patients of different races, including non-Hispanic White, non-Hispanic Black, Hispanic, and other (Asian and unknown). Data were compared in White versus non-White skin. RESULTS: Sixty-three DM and 9 ADM patients met the inclusion criteria. There was a shorter time to treatment initiation in White versus non-White patients, with a median number of 8 days compared with 21 days, respectively ( p = 0.05). Kaplan-Meier curves showed prolonged time to diagnosis and treatment in all other races when compared with White patients ( p = 0.03). DISCUSSION: It took clinicians longer to diagnose and treat DM and ADM in patients of color. The trends observed emphasize the importance of increasing dermatology education of non-White skin to improve detection and treatment of DM and ADM and minimize health disparities.

Two Cases of Venous Thromboembolism Shortly After Adenovirus-Based COVID-19 Vaccination.

As the coronavirus disease 2019 (COVID-19) global pandemic continues, multiple vaccines have been developed to decrease infection rate and number of deaths. Vaccine administration is especially important as new COVID-19 variants emerge. While the number of severe thromboembolic events reported after adenovirus-based vaccination has gained attention, there is little information regarding the presentation and management of post-vaccination venous thromboembolism (VTE). Here, we present two cases of VTE after the Janssen vaccine administration. In the first case, a 98-year-old African American female with hypertension developed bilateral lower extremity edema that evolved into unilateral lower extremity edema 20-35 days following the Janssen vaccine administration. She was found to have an extensive unilateral proximal femoral deep vein thrombosis (DVT) 35 days after the vaccination. In the second case, a 64-year-old African American female developed ecchymosis and unilateral edema six days after the Janssen vaccine administration. She was found to have proximal superficial vein thrombosis two days later. In both cases, laboratory data, including platelets and anti-heparin antibodies were within normal limits. Thus, VTE may be an adverse effect of the Janssen vaccine or any adenovirus-based vaccine, but further surveillance and investigation to elucidate this association are necessary. We advise practitioners to have a high index of suspicion for thrombosis after Janssen vaccine administration, regardless of the presence of thrombocytopenia, and avoidance of heparin products until heparin antibody results return.

A Case of Microscopic Polyangiitis Complicated by Mucormycosis: A Dangerous Balancing Act.

Microscopic polyangiitis (MPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis marked by renal involvement, which often leads to rapidly progressive glomerulonephritis. Immunosuppressive treatment is necessary to prevent irreparable organ damage. On the other hand, mucormycosis is a rare and devastating opportunistic fungal infection with a high mortality rate in both immunosuppressed and immunocompetent individuals. It requires a high index of suspicion at the time of diagnosis since any delay in treatment may lead to severe morbidity or death. Here, we present the case of a diabetic patient diagnosed with MPA who received partial induction treatment, subsequently developed mucormycosis, survived, yet required continued immunosuppressive treatment for active MPA while imaging was concerning for a persistent mucormycosis infection. This case highlights the barriers to early mucormycosis detection specific to vasculitis patients, mucormycosis considerations unique to the rheumatologic population, and discusses how to balance immunosuppressive treatment in the setting of a deadly opportunistic infection.

Association of Hydroxychloroquine Dose With Adverse Cardiac Events in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether hydroxychloroquine (HCQ) dose is associated with adverse cardiac outcomes in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE taking HCQ and with ≥1 echocardiogram followed at a tertiary care center in the Bronx, New York between 2005 and 2021 were included. The HCQ weight-based dose at the HCQ start date was the main exposure of interest. The outcome was incident all-cause heart failure with reduced ejection fraction (HFrEF), life-threatening arrhythmia, or cardiac death. We used Fine-Gray regression models with death as a competing event to study the association of HCQ dose with the outcome. Due to a significant interaction between smoking and HCQ exposure, models were stratified by smoking status. Propensity score analysis was performed as a secondary analysis. RESULTS: Of 294 patients, 37 (13%) developed the outcome over a median follow-up time of 7.9 years (interquartile range [IQR] 4.2-12.3 years). In nonsmokers (n = 226), multivariable analysis adjusted for age, body mass index, hypertension, chronic kidney disease, diabetes mellitus, and thromboembolism showed that higher HCQ weight-based doses were not associated with an increased risk of the outcome (subdistribution hazard ratio [HR] 0.62 [IQR 0.41-0.92], P = 0.02). Similarly, higher baseline HCQ doses were not associated with a higher risk of the outcome among smokers (n = 68) (subdistribution HR 0.85 [IQR 0.53-1.34] per mg/kg, P = 0.48). Propensity score analysis showed comparable results. CONCLUSION: Higher HCQ doses were not associated with an increased risk of HFrEF, life-threatening arrhythmia, or cardiac death among patients with SLE and may decrease the risk among nonsmokers.

In-Vitro Growth Kinetics of Mesenchymal Stem Cells in Cytotoxicity Tests Using Low-Diluted Viscum Album.

INTRODUCTION: The use of mesenchymal stem cells (MSC) in cytotoxicity tests is an in-vitro alternative model for predicting initial doses. Homeopathic medicines may stimulate the immune system to combat a pathology effectively and have been used for over two centuries. Viscum album (VA) extracts are widely used in the treatment of cancer, due to their immunomodulatory, cytotoxic and pro-apoptotic properties. OBJECTIVE: This study aimed to evaluate the in-vitro growth kinetics of canine MSC in relation to cytotoxicity, cell differentiation and expression of pluripotentiality markers, using a VA preparation at the D1D2 (1×10-1, 1×10-2 potency (VAD1D2). METHODS: MSC were obtained from adipose tissue sampled from a healthy dog that was undergoing an elective veterinary procedure and with its owner's permission. The experiments were performed in three groups: MSC treated with VAD1D2 or diluent or untreated (control). The cytotoxicity was evaluated by MTT assay. The differentiation was induced in three lineages, and apoptotic cell labeling was performed by an Annexin-V test. RESULTS: At the concentration of 10 µL/mL of VA, the number of cells after in-vitro culture was maintained when compared with the control (untreated) group. A significant and gradual decrease in cell viability was recorded as VA concentrations increased. The apoptosis analysis showed that VA at 20 µL/mL presented absolute percentages of initial apoptosis twice as high as at 10 µL/mL, which was similar to the control (untreated group). CONCLUSION: The results suggest that the use of efficient methods to assess the in-vitro cytotoxicity of VA-based homeopathic medicines using MSC lineages may predict the potential action at different concentrations. These findings demonstrated that VAD1D2 interferes with canine MSC growth kinetics.

Kaurenoic acid nanocarriers regulates cytokine production and inhibit breast cancer cell migration.

Breast cancer is the type of cancer with the highest incidence in women around the world. Noteworthy, the triple-negative subtype affects 20% of the patients while presenting the highest death rate among subtypes. This is due to its aggressive phenotype and the capability of invading other tissues. In general, tumor-associated macrophages (TAM) and other immune cells, are responsible for maintaining a favorable tumor microenvironment for inflammation and metastasis by secreting several mediators such as pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α, chemokines like CCL2, and other proteins, as metalloproteinases of matrix (MMP). On the other hand, immunomodulatory agents can interfere in the immune response of TAM and change the disease prognosis. In this work, we prepared nanostructured lipid carriers containing kaurenoic acid (NLC-KA) to evaluate the effect on cytokine production in vitro of bone marrow-derived macrophages (BMDM) and the migratory process of 4 T1 breast cancer cells. NLC-KA prepared from a blend of natural lipids was shown to have approximately 90 nm in diameter with low polydispersity index. To test the effect on cytokine production in vitro in NLC-KA treated BMDM, ELISA assay was performed and pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α were quantified. The formulation reduced the secretion of IL-1ß and TNF-α cytokines while presenting no hemolytic activity. Noteworthy, an anti-migratory effect in 4 T1 breast cancer cells treated with NLC-KA was observed in scratch assays. Further, MMP9 and CCL2 gene expressions in both BMDM and 4 T1 treated cells confirmed that the mechanism of inhibition of migration is related to the blockade of this pathway by KA. Finally, cell invasion assays confirmed that NLC-KA treatment resulted in less invasiveness of 4 T1 cells than control, and it is independent of CCL2 stimulus or BMDM direct stimulus. Ultimately, NLC-KA was able to regulate the cytokine production in vitro and reduce the migration of 4 T1 breast cancer cells by decreasing MMP9 gene expression.

A Case of Latent Plasmodium Falciparum Malaria in a Patient With Coexisting Systemic Lupus Erythematosus (SLE) and Neuromyelitis Optica Spectrum Disorder (NMOSD).

Malaria is a global health concern with high morbidity and mortality. It is often attributed to the Plasmodium (P.) falciparum species, particularly in sub-Saharan Africa, and it normally has an incubation period of seven to 14 days. Dormant disease secondary to P. vivax and P. ovale is well-reported, yet only a handful of cases report dormant malaria secondary to P. falciparum. Even though malaria is significantly less common in the United States in comparison to other parts of the world, it is still a growing concern given international travel from endemic regions and a growing immunocompromised population. Here, we present a case of Plasmodium falciparum malaria in a patient with systemic lupus erythematosus (SLE) with neuromyelitis optica spectrum disorder (NMOSD) and renal transplant without travel to sub-Saharan Africa in 10 years.

Optimizing two-stage surgery by expanding single-stage nasal reconstruction in the COVID-19 era.

The COVID-19 pandemic led to a decrease in the number of operating rooms available. Single-stage islanded forehead flaps have emerged as a good alternative to the classic frontal flap helping to diminish the surgical waiting list. We present our case series of 6 patients reconstructed with islanded forehead flaps between February and July 2020.The purpose of this report is to assess the advantages and disadvantages of this technique in order to inform which subgroup of patients may benefit from the one-stage flap, now the pandemic is better controlled.

Diseño y aplicación de un cuestionario de detección precoz en salud mental infantil / Design and application of an early detection questionnaire in child mental health

Los problemas en salud mental infantil son frecuentes, complejos y pueden conllevar un riesgo en el desarrollo. La prevención en salud mental es un compromiso colectivo, especialmente por parte de las instituciones que atienden la primera infancia: la escuela y la consulta pediátrica. El objetivo de esta investigación es validar un instrumento diseñado ad hoc de detección precoz en salud mental para la primera infancia. En el diseño del instrumento, denominado Detectar para Prevenir–Salud Mental Infantil–25 (DxP-SMI-25), se tuvo en cuenta la literatura previa y las limitaciones actuales en la detección precoz en salud mental. El contenido del cuestionario se validó mediante un juicio de expertos y se aplicó el cuestionario, junto al Ages & Statges Questionnaires: Social-Emotional-2, con el fin de obtener la validez de criterio. El instrumento diseñado muestra una buena predisposición y permite una evaluación global del desarrollo.

Child mental health problems are frequent, complex and can lead to developmental risk. Prevention in mental health is a collective commitment, especially on the part of the institutions that care for early childhood: the school and the pediatric office. The aim of this paper is to validate an ad hoc instrument designed for early mental health screening in early childhood. The design of the instrument, called Detectar para Prevenir- Salud Mental Infantil-25 (DxP-SMI-25, Detect to Prevent- Children's Mental Health-25), took into account previous literature and current limitations in early mental health screening. The content of the questionnaire was validated by means of expert judgment and the questionnaire was applied, together with the Ages & Statges Questionnaires: Social-Emotional-2, in order to obtain criterion validity. The designed instrument shows a good predisposition and allows a global assessment of development.

Cascade of care for office-based buprenorphine treatment in Bronx community clinics.

INTRODUCTION: The cascade of care for opioid use disorder (OUD) has been described at the population level to inform health policy and in health care systems, programs, and communities to guide targeted interventions. Office-based buprenorphine treatment is essential for expanding access to OUD treatment; however, few studies examine the cascade of care specifically for office-based buprenorphine treatment. Our objective was to describe a cascade of care for patients referred for office-based buprenorphine treatment in the primary care setting. METHODS: We conducted a retrospective cohort study of patients with OUD who were referred for office-based buprenorphine treatment within a large, urban health care system between 2018 and 2019. Our primary outcomes included completion of each step of the buprenorphine treatment cascade of care: 1) referred for treatment, 2) scheduled initial visit, 3) completed initial visit, 4) initiated buprenorphine treatment, and 5) retained in treatment at 90 days. We constructed a cascade of care by calculating proportions of patients identified at every step, starting with the total number of patients referred for treatment as the first step. We extracted data from the program's referral database and electronic medical record system. We compared characteristics of patients referred who initiated buprenorphine to those referred who did not initiate buprenorphine treatment using chi-squared tests and t-tests. To account for the hierarchical nature of the data, we conducted a Generalized Estimating Equation (GEE) modeling to test the differences in attrition rates among the steps of the cascade of care. RESULTS: In the 24-month period between 2018 and 2019, 226 patients were referred for office-based buprenorphine treatment at Montefiore's Buprenorphine Treatment Network. Patients' mean age at referral was 47 years, and most were male (68.6%), Hispanic (49.6%), and publicly insured (75.7%). Among all patients, 182 (80.5%) were scheduled for an initial visit, 142 (62.8%) completed the initial visit, 134 (59.3%) initiated buprenorphine treatment, and 95 (42.0%) were retained in treatment at 90 days. 37.2% of all patients referred did not complete the initial visit. A GEE model showed that attrition is significantly steeper in the first two steps of the cascade of care, compared to the later three steps (AOR = 1.95, 95% CI = 1.31-2.91, p < 0.05). Compared to referred patients who did not initiate treatment, those referred who initiated treatment were more likely to be using non-prescribed buprenorphine at time of referral (19.4% vs. 5.4%, p < 0.05) and be self-referred (22.4% vs. 9.8%, p < 0.05). CONCLUSION: Our study is the first to describe a cascade of care for office-based buprenorphine treatment in a large health care system. The study observed the steepest attrition in the first two steps of the cascade of care, where more than a third of patients referred did not complete the initial visit. Patients who were self-referred, or using non-prescribed buprenorphine were more likely to initiate treatment. A cascade of care specific for office-based buprenorphine can inform future efforts to improve linkage to care.