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The growing threat of emergent multidrug-resistant enteric bacterial pathogens, and their adopted virulence properties are directing to find alternative antimicrobials and/or development of dietaries that can improve host gut health and/or defense. Recently, we found that modified Lactobacillus casei (Lc + CLA) with increased production of conjugated linoleic acid has antimicrobial and other beneficial properties. Further, prebiotic alike products such as berry pomace extracts (BPEs), increase the growth of probiotics and inhibit the growth of certain bacterial pathogens. In this study, we evaluated the antibacterial effect of genetically modified Lc + CLA along with BPEs against major enteric pathogen Salmonella enterica serovar Typhimurium (ST). In mixed culture condition, the growth of ST was significantly reduced in the presence of Lc + CLA and/or BPEs. Bacterial cell-free cultural supernatant (CFCS) collected from wild-type Lc or modified Lc + CLA strains also inhibited the growth and survival of ST, and those inhibitory effects were enhanced in the presence of BPEs. We also found that the interaction of the pathogen with cultured host (HD-11 and INT-407) cells were also altered in the presence of either Lc or Lc + CLA strain or their CFCSs significantly. Furthermore, the relative expression of genes related to ST virulence and physicochemical properties of ST was altered by the effect of CFCSs of either Lc or Lc + CLA. These findings indicate that a diet containing synbiotic, specifically linoleic acid, over-produced Lc + CLA and prebiotic product BPEs, might have the potential to be effective in controlling ST growth and pathogenesis.

Background Majority of enteric infections are foodborne and antimicrobials including antibiotics have been used for their control and treatment. However, probiotics or prebiotics or their combination offer a potential alternative intervention strategy for improving the host health and preventing foodborne pathogen colonization/infections in reservoir. Further, bioengineered probiotics expressing bioactive products to achieve specific function is highly desirable. Recently, we over-expressed mcra (myosin cross-reactive antigen) gene in Lactobacillus casei (Lc) and developed a bioengineered probiotics Lc + CLA which produce higher amounts of metabolites including conjugated linoleic acid (CLA). Furthermore, we also reported that prebiotic like components such as berry pomace (byproduct) phenolic extracts (BPEs) can enhance the growth of probiotics and improved the beneficial effects of probiotics. In this study, we evaluated the antimicrobial effect of modified Lc + CLA in combination of BPEs on growth, survival and pathogenesis of enterohemorrhagic Escherichia coli (EHEC). Results In mixed culture condition, the growth of EHEC was significantly reduced in the presence Lc + CLA and/or BPEs. Cell-free cultural supernatant (CFCS) collected from Lc or Lc + CLA strain also inhibited the growth and survival of EHEC and the inhibitory effects of CFCSs against EHEC were enhanced in the presence of BPEs in concentration dependent manner. Interaction between EHEC and intestinal epithelial INT-407 cells were also altered significantly in the presence of either Lc or Lc + CLA strain or their CFCSs with or without BPEs. The expression of multiple virulence genes and physicochemical properties of EHEC were also altered when the bacterial cells were pretreated with CFCSs and/or BPEs. Conclusions These results showed that diet containing bioactive Lc + CLA and natural prebiotic like component such as BPEs might be an effective way to prevent foodborne infections with EHEC.

Objective Our epilepsy population recently experienced the acute effects of the COVID‐19 pandemic in New York City. Herein, we aimed to determine patient‐perceived seizure control during the surge, specific variables associated with worsened seizures, the prevalence of specific barriers to care, and patient‐perceived efficacy of epilepsy care delivered via telephone and live video visits during the pandemic. Methods We performed a cross‐sectional questionnaire study of adult epilepsy patients who had a scheduled appointment at a single urban Comprehensive Epilepsy Center (Montefiore Medical Center) between March 1, 2020 and May 31, 2020 during the peak of the COVID‐19 pandemic in the Bronx. Subjects able to answer the questionnaire themselves in English or Spanish were eligible to complete a one‐time survey via telephone or secure online platform (REDCap). Results Of 1212 subjects screened, 675 were eligible, and 177 adequately completed the questionnaire. During the COVID‐19 pandemic, 75.1% of patients reported no change in seizure control, whereas 17.5% reported that their seizure control had worsened, and 7.3% reported improvement. Subjects who reported worsened seizure control had more frequent seizures at baseline, were more likely to identify stress and headaches/migraines as their typical seizure precipitants, and were significantly more likely to report increased stress related to the pandemic. Subjects with confirmed or suspected COVID‐19 did not report worsened seizure control. Nearly 17% of subjects reported poorer epilepsy care, and 9.6% had difficulty obtaining their antiseizure medications; these subjects were significantly more likely to report worse seizure control. Significance Of the nearly 20% of subjects who reported worsened seizure control during the COVID‐19 pandemic, stress and barriers to care appear to have posed the greatest challenge. This unprecedented pandemic exacerbated existing and created new barriers to epilepsy care, which must be addressed.

Background Infection with the novel severe acute respiratory syndrome coronavirus 2 has been associated with a hypercoagulable state. Emerging data from China and Europe have consistently shown an increased incidence of venous thromboembolism (VTE). We aimed to identify the VTE incidence and early predictors of VTE at our high-volume tertiary care center. Methods We performed a retrospective cohort study of 147 patients who had been admitted to Temple University Hospital with coronavirus disease 2019 (COVID-19) from April 1, 2020 to April 27, 2020. We first identified the VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]) incidence in our cohort. The VTE and no-VTE groups were compared by univariable analysis for demographics, comorbidities, laboratory data, and treatment outcomes. Subsequently, multivariable logistic regression analysis was performed to identify the early predictors of VTE. Results The 147 patients (20.9% of all admissions) admitted to a designated COVID-19 unit at Temple University Hospital with a high clinical suspicion of acute VTE had undergone testing for VTE using computed tomography pulmonary angiography and/or extremity venous duplex ultrasonography. The overall incidence of VTE was 17% (25 of 147). Of the 25 patients, 16 had had acute PE, 14 had had acute DVT, and 5 had had both PE and DVT. The need for invasive mechanical ventilation (adjusted odds ratio, 3.19; 95% confidence interval, 1.07-9.55) and the admission D-dimer level ≥1500 ng/mL (adjusted odds ratio, 3.55; 95% confidence interval, 1.29-9.78) were independent markers associated with VTE. The all-cause mortality in the VTE group was greater than that in the non-VTE group (48% vs 22%; P = .007). Conclusions Our study represents one of the earliest reported from the United States on the incidence rate of VTE in patients with COVID-19. Patients with a high clinical suspicion and the identified risk factors (invasive mechanical ventilation, admission D-dimer level ≥1500 ng/mL) should be considered for early VTE testing. We did not screen all patients admitted for VTE; therefore, the true incidence of VTE could have been underestimated. Our findings require confirmation in future prospective studies.

In recent years, the development of a nano-conjugate system for drug delivery applications has gained attention among researchers. Keeping this in mind, in this study, we developed a doxorubicin–platinum conjugate system that targeted breast cancer cell lines. To achieve this, we developed platinum nanoparticles using polyvinylpyrrolidone (PVP). High resolution-transmission electron microscopy (HR-TEM) revealed the occurrence of octopod-shaped platinum nanoparticles. Subsequently, doxorubicin (DOX) was conjugated on the surface of the as-prepared platinum octopods via an in situ stirring method. The physicochemical characterization of the doxorubicin–platinum conjugate system revealed that the PVP of PtNPs interacts with the NH2 group of doxorubicin via electrostatic interaction/hydrogen bonding. Besides, the doxorubicin–platinum conjugate system exhibited a sustained drug release profile within the cancer cells. Furthermore, the evaluation of the in vitro anticancer efficacy of the doxorubicin–platinum conjugate system in breast cancer cells (MCF-7 and MDA-MB-231) unveiled the induction of apoptosis via intracellular ROS and DNA damage, rather than free DOX and PtNPs. Remarkably, we also perceived that the doxorubicin–platinum conjugate system was strong enough to down-regulate the PI3K/AKT signalling pathway. As a result, the tumour suppressor gene PTEN was activated, which led to the stimulation of a mitochondrion-based intrinsic apoptotic pathway and its downstream caspases, triggering cell death. Hence, our findings suggested that a biologically stable doxorubicin–platinum conjugate system could be an imperative therapeutic agent for anticancer therapy in the near future.

This is an interesting case of ascending penetrating aortic ulcer (PAU) leading to pseudoaneurysm and eventually type A aortic dissection and peri-aortic hematoma. PAUs are common clinical manifestations, however, uncommonly lead to pseudoaneurysms that cause aortic dissection.

This is a case of a patient diagnosed with anterior ST-elevation myocardial infarction (STEMI) with a ventricular paced rhythm after the patient underwent a femoral-femoral bypass surgery for severe peripheral vascular disease. The case highlights the diagnosis of STEMI in the setting of paced rhythm in the appropriate clinical setting.

This is an interesting cardiovascular imaging and coronary angiography case of a 67-year-old female patient who presented with chest pain, abnormal electrocardiogram (EKG), and heart failure who was subsequently found to have spontaneous coronary artery dissection (SCAD) and Takotsubo cardiomyopathy (TCM) on imaging studies. The case presentation highlights the importance of imaging studies and prompt diagnosis in these patients. This study may also highlight the need for early medical intervention in patients with suspected systolic dysfunction due to either of these pathophysiologic processes.

Loss-of-function mutations of the s-cell ATP-sensitive potassium channels (KATP) cause the most common and severe form of congenital hyperinsulinism (KATPHI), a disorder of s-cell function characterized by severe hypoglycemia. Children with KATPHI are typically unresponsive to medical therapy and require pancreatectomy for intractable hypoglycemia. We tested the hypothesis that inhibition of insulin receptor signaling may prevent hypoglycemia in KATPHI. To test this hypothesis, we examined the effect of an antibody allosteric inhibitor of the insulin receptor, XMetD, on fasting plasma glucose in a mouse model of KATPHI (SUR-1-/- mice). SUR-1-/- and wild-type mice received twice weekly intraperitoneal injections of either XMetD or control antibody for 8 wks. Treatment with XMetD significantly decreased insulin sensitivity, and increased hepatic glucose output and fasting plasma glucose. These findings support the potential use of insulin receptor antagonists as a therapeutic approach to control the hypoglycemia in congenital hyperinsulinism.

HIV-associated neurocognitive impairments that impact daily function persist in the era of effective antiretroviral therapy. Cognitive training, a promising low-cost intervention, has been shown to improve neurocognitive functioning in some clinical populations. We tested the feasibility, acceptability, and preliminary effects of computerized cognitive training to improve working memory in persons living with HIV infection (PLWH) and working memory impairment. In this randomized clinical trial, we assigned 21 adult PLWH to either an experimental cognitive training intervention or an attention-matched control training intervention. Participants completed 12 training sessions across 10 weeks with assessments at baseline and post-training. Session attendance was excellent and participants rated the program positively. Participants in the experimental arm demonstrated improved working memory function over time; participants in the control arm showed no change. Our results suggest that cognitive training may be a promising intervention for working memory impairment in PLWH and should be evaluated further.

Background and Purpose— Primary stroke center (PSC) certification was established to identify hospitals providing evidence-based care for stroke patients. The numbers of PSCs certified by Joint Commission (JC), Healthcare Facilities Accreditation Program, Det Norske Veritas, and State-based agencies have significantly increased in the past decade. This study aimed to evaluate whether PSCs certified by different organizations have similar quality of care and in-hospital outcomes. Methods— The study population consisted of acute ischemic stroke patients who were admitted to PSCs participating in Get With The Guidelines-Stroke between January 1, 2010, and December 31, 2012. Measures of care quality and outcomes were compared among the 4 different PSC certifications. Results— A total of 477 297 acute ischemic stroke admissions were identified from 977 certified PSCs (73.8% JC, 3.7% Det Norske Veritas, 1.2% Healthcare Facilities Accreditation Program, and 21.3% State-based). Composite care quality was generally similar among the 4 groups of hospitals, although State-based PSCs underperformed JC PSCs in a few key measures, including intravenous tissue-type plasminogen activator use. The rates of tissue-type plasminogen activator use were higher in JC and Det Norske Veritas (9.0% and 9.8%) and lower in State and Healthcare Facilities Accreditation Program certified hospitals (7.1% and 5.9%) ( P Conclusions— Among Get With The Guidelines-Stroke hospitals with PSC certification, acute ischemic stroke quality of care and outcomes may differ according to which organization provided certification. These findings may have important implications for further improving systems of care.

Brain imaging studies have identified multiple neuronal networks and circuits in the brain with altered functioning in patients with schizophrenia. These include the hippocampo-cerebello-cortical circuit, the prefrontal-thalamic-cerebellar circuit, functional integration in the bilateral caudate nucleus, and the salience network consisting of the insular cortex, parietal anterior cingulate cortex, and striatum, as well as limbic structures. Attributing psychotic symptoms to any of these networks in schizophrenia is confounded by the disruption of these networks in schizophrenic patients. Such attribution can be done with isolated dysfunction in any of these networks with concurrent psychotic symptoms. We present the case of a patient who presents with new-onset hallucinations and a stroke in brain regions similar to the salience network (insular cortex, parietal cortex, and striatum). The implication of these findings in isolating psychotic symptoms of the salience network is discussed.

Probiotics are recognized for outcompeting pathogenic bacteria by competitive receptor-mediated colonization and secretion of functional metabolites which are antimicrobial against certain microbes as well as improving host’s gut health and immunity. Recently, we have constructed a bioactive Lactobacillus casei (LC) strain, LC(+mcra), by inserting mcra (myosin cross-reactive antigen) gene, which stimulates the conversion of conjugated linoleic acids. In this study, we evaluated the modulation of gut microbiome and protective roles of LC(+mcra) against pathogenic Salmonella enterica serovar Typhimurium (ST) and enterohemorrhagic E. coli (EHEC) infections in BALB/cJ mice. We observed that LC(+mcra) colonized efficiently in mice gut intestine and competitively reduced the infection with ST and EHEC in various locations of small and large intestine, specifically cecum, jejunum, and ileum (p

An artificial cell-signaling pathway is developed that capitalizes on the T-cell's innate extravasation ability and transforms it into a vector (T-cell Biofactory) for synthesizing calibrated amounts of engineered proteins in vivo. The modularity of this pathway enables reprogramming of the T-cell Biofactory to target biomarkers on different disease cells, e.g. cancer, viral infections, autoimmune disorders. It can be expected that the T-cell Biofactory leads to a "living drug" that extravasates to the disease sites, assesses the disease burden, synthesizes the calibrated amount of engineered therapeutic proteins upon stimulation by the diseased cells, and reduces targeting of normal cells.

The development of novel approaches in the biosynthesis of gold nanoparticles has significantly gained tremendous attention in the medical field. In the present study, an aqueous seaweed extract of the marine brown algae S. ilicifolium has been used for the synthesis of hybrid gold nanoparticles. The gold nanoparticles were found to be near-spherical in shape and size of 20–25 nm. Altogether, phytoconstituents such as polyols, proteins, and aromatic compounds play an important role in capping and stabilizing the hybrid gold nanoparticles. The hybrid gold nanoparticles were found to be crystalline as evidence by X-ray diffraction studies. We also demonstrated that synthesized hybrid gold nanoparticles exert antibacterial activity at 48 ± 1.36 μg mL−1 and cause selective cell death of Staphylococcus aureus by generating an enhanced level of intracellular ROS. Further, upon treatment with hybrid gold nanoparticles (24 ± 1.94 μgmL−1), the breast cancer cell lines showed more apoptotic features such as loss of membrane integrity and chromatin condensation when compared to the control groups. The biocompatibility assessment of hybrid gold nanoparticles in Artemia salina revealed that it does not elicit any lethal effect even at 250 μgmL−1. Taken together, these findings suggest that a hybrid nanoparticle from S. illicifolium is eco-friendly, has selective antibacterial activity, and effectively kills breast cancer cells by inducing apoptosis.

Probiotics, particularly lactic acid bacteria, are biologic agents which limit the growth, virulence, and survival/colonization of various enteric bacterial pathogens and serve as potential alternatives to antibiotics. Mechanisms that contribute to this antimicrobial effect include producing bioactive metabolites/acids, increasing nutrient and receptor-mediated competition, and modulating gut microbiome ecology. However, these functions of common probiotic strains are limited due to the finite quantity of metabolites they produce and their total number in the gut ecosystem. Conjugated linoleic acids (CLAs), critical metabolites of Lactobacillus, have multiple beneficial effects on human health including anti-carcinogenesis, anti-inflammation, anti-oxidation, and anti-pathogenicity. In this study, we aim to overexpress the myosin cross-reactive antigen gene (mcra) in Lactobacillus casei (LC) to enhance the production of CLA and investigate its effectiveness against enteric bacterial pathogens, specifically Salmonella enterica serovar Typhimurium (ST) and enterohaemorrhagic Escherichia coli (EHEC). By inserting mcra in L. casei, we generated LC-CLA and found the total linoleic acid production by an individual bacterial cell was raised by 21-fold. The adherence ability of LC-CLA on human epithelial cells increased significantly and LC-CLA competitively excluded both ST and EHEC in a mixed-culture condition. Furthermore, LC-CLA significantly altered the physicochemical properties, biofilm formation abilities, interactions with host cells of both ST and EHEC, and triggered anti-inflammatory activities of host cells. These findings offer insights on applying a genetically engineered probiotic to control gut intestinal infections caused by ST and EHEC and prevent foodborne enteric illness in human.

Global health care manufacturer Novo Nordisk commissioned research regarding awareness of drug safety department activities and potential to increase patient feedback. Objectives were to examine patients' knowledge of pharmaceutical manufacturers' responsibilities and efforts regarding drug safety, their perceptions and experiences related to these efforts, and how these factors influence their thoughts and behaviors. Data were collected before and after respondents read a description of a drug safety department and its practices.We conducted quantitative survey research across 608 health care consumers receiving treatment for diabetes in the United States, Germany, United Kingdom, and Italy. This research validated initial, exploratory qualitative research (across 40 comparable consumers from the same countries) which served to guide design of the larger study.Before reading a drug safety department description, 55% of respondents were unaware these departments collect safety information on products and patients. After reading the description, 34% reported the department does more than they expected to ensure drug safety, and 56% reported "more confidence" in the industry as a whole. Further, 66% reported themselves more likely to report an adverse event or product complaint, and 60% reported that they were more likely to contact a drug safety department with questions. The most preferred communication methods were websites/online forums (39%), email (27%), and telephone (25%).Learning about drug safety departments elevates consumers' confidence in manufacturers' safety efforts and establishes potential for patients to engage in increased self-monitoring and reporting. Study results reveal potentially actionable insights for the industry across patient and physician programs and communications.

The diagnosis and management of parotitis can be challenging. Patients often present with pain and edema in the neck, jaw, head, and ear due to congestion of the gland. Parotitis is typically caused by an infection within the parotid gland and surrounding lymph nodes, and the infection can spread to nearby cervical fascial planes and cause major complications if not managed successfully. Specific guidelines for the outpatient management of parotitis are limited, and outpatient treatment failures are common, requiring inpatient therapy with multiple broad-spectrum antibiotics. In the current case, a comprehensive patient-centered approach was used to treat a woman whose overlapping clinical conditions, lifestyle, and work factors led to an infection of the parotid gland.

Background This study aims to improve the rate of folic acid supplementation to adolescent women with epilepsy on an antiepileptic drug (AED) regimen seen by the pediatric neurology providers at the Children's Hospital at Montefiore, in compliance with the 2009 American Academy of Neurology and American Epilepsy Society practice parameter. Methods We designed a quality improvement study with implementation of a series of interventions and compared folic acid supplementation rates before and after intervention. We made additional comparisons based on specific age groups (12 to 15 years and 16 to 21 years) and a diagnosis with or without developmental impairment. Results A review of 1850 charts from 2004 to 2015 showed an average folic acid prescription rate of 41%. Supplementation rates gradually increased to 52.2%, 58.5%, 60.3%, and finally up to 81.6% after this respective intervention: initial email reminder, provider education, posting signs in examination rooms, and implementation of an electronic medical record best practice advisory. There was improvement across all categories, in both age groups (12 to 15 years and 16 to 21 years) and in those with or without developmental impairment. There was a trend for higher compliance rates in adolescents without developmental impairment. Conclusions Our interventions resulted in an increase in folic acid supplementation rates of adolescent women with epilepsy. These results are encouraging. We plan to extend education about the recommendations for folic acid supplementation to non-neurology providers, as well as expand to apply our interventions and assess adherence to other defined epilepsy quality measures.

The unpredictability of seizures causes distress to patients with epilepsy and their caretakers. To date, no studies have explored seizure prediction specifically in the pediatric population. If the period of time preceding a seizure can be reliably identified, either by child or caretaker, there may be a role for pre-emptive interventions. The aim of this study was to investigate caretaker seizure prediction. A questionnaire was distributed to caretakers of patients with epilepsy. The patients were 0-21years old and experienced ≥1 seizure within the past year. We excluded patients with non-epileptic seizures or daily seizures. One hundred and fifty of 240 questionnaires met criteria. Of these, 32 (21.6%) caretakers indicated a positive report of seizure prediction. Age of seizure onset was earlier in the positive predictive group (3.3±3.3years) than in the non-predictor group (5.3±4.8years) (p=0.01). The most common pre-ictal symptoms reported were being tired, hazy look, and sleepiness. A total of 76.6% of caretakers reported at least one seizure precipitant. The prevalence of positive caretaker seizure prediction in this study is similar to that of seizure self-prediction in adult studies. These findings will be used to design prospective online or electronic diary studies to further investigate the caretaker's, as well as children's, perspectives on seizure prediction. We anticipate that this investigation may lead to novel treatments during times of high seizure risk.