Resveratrol as a Promising Nutraceutical: Implications in Gut Microbiota Modulation, Inflammatory Disorders, and Colorectal Cancer.

Natural products have been a long-standing source for exploring health-beneficial components from time immemorial. Modern science has had a renewed interest in natural-products-based drug discovery. The quest for new potential secondary metabolites or exploring enhanced activities for existing molecules remains a pertinent topic for research. Resveratrol belongs to the stilbenoid polyphenols group that encompasses two phenol rings linked by ethylene bonds. Several plant species and foods, including grape skin and seeds, are the primary source of this compound. Resveratrol is known to possess potent anti-inflammatory, antiproliferative, and immunoregulatory properties. Among the notable bioactivities associated with resveratrol, its pivotal role in safeguarding the intestinal barrier is highlighted for its capacity to prevent intestinal inflammation and regulate the gut microbiome. A better understanding of how oxidative stress can be controlled using resveratrol and its capability to protect the intestinal barrier from a gut microbiome perspective can shed more light on associated physiological conditions. Additionally, resveratrol exhibits antitumor activity, proving its potential for cancer treatment and prevention. Moreover, cardioprotective, vasorelaxant, phytoestrogenic, and neuroprotective benefits have also been reported. The pharmaceutical industry continues to encounter difficulties administering resveratrol owing to its inadequate bioavailability and poor solubility, which must be addressed simultaneously. This report summarizes the currently available literature unveiling the pharmacological effects of resveratrol.

Harnessing the probiotic properties and immunomodulatory effects of fermented food-derived Limosilactobacillus fermentum strains: implications for environmental enteropathy.

Introduction: Environmental enteropathy (EE), a chronic small intestine disease characterized by gut inflammation, is widely prevalent in low-income countries and is hypothesized to be caused by continuous exposure to fecal contamination. Targeted nutritional interventions using potential probiotic strains from fermented foods can be an effective strategy to inhibit enteric pathogens and prevent chronic gut inflammation. Methods: We isolated potential strains from fermented rice water and lemon pickle and investigated their cell surface properties, antagonistic properties, adhesion to HT-29 cells, and inhibition of pathogen adherence to HT-29 cells. Bacteriocin-like inhibitory substances (BLIS) were purified, and in vivo, survival studies in Caenorhabditis elegans infected with Salmonella enterica MW116733 were performed. We further checked the expression pattern of pro and anti-inflammatory cytokines (IL-6, IL8, and IL-10) in HT-29 cells supplemented with strains. Results: The strains isolated from rice water (RS) and lemon pickle (T1) were identified as Limosilactobacillus fermentum MN410703 and MN410702, respectively. Strains showed probiotic properties like tolerance to low pH (pH 3.0), bile salts up to 0.5%, simulated gastric juice at low pH, and binding to extracellular matrix molecules. Auto-aggregation of T1 was in the range of 85% and significantly co-aggregated with Klebsiella pneumoniae, S. enterica, and Escherichia coli at 48, 79, and 65%, respectively. Both strains had a higher binding affinity to gelatin and heparin compared to Bacillus clausii. Susceptibility to most aminoglycoside, cephalosporin, and macrolide classes of antibiotics was also observed. RS showed BLIS activity against K. pneumoniae, S. aureus, and S. enterica at 60, 48, and 30%, respectively, and the protective effects of BLIS from RS in the C. elegans infection model demonstrated a 70% survival rate of the worms infected with S. enterica. RS and T1 demonstrated binding efficiency to HT-29 cell lines in the 38-46% range, and both strains inhibited the adhesion of E. coli MDR and S. enterica. Upregulation of IL-6 and IL-10 and the downregulation of IL-8 were observed when HT-29 cells were treated with RS, indicating the immunomodulatory effects of the strain. Discussion: The potential strains identified could effectively inhibit enteric pathogens and prevent environmental enteropathy.

Faculty Experiences Related to Career Advancement and Success in Academic Medicine.

Phenomenon: Faculty career success in academic medicine is complex. Dynamic interactions among faculty and between faculty and their socio-cultural working environments contribute to the mystique of academic advancement. There are few empirical studies that analyze the social practice of faculty career advancement in academic medicine, especially those that focus on relations between individual and environmental contexts. This study aimed to investigate various faculty members' experiences around career advancement in a medical school. Through the analytical lens of Bourdieu's theory of practice, we focused on the relationship among individuals, positions, and environmental contexts.Approach: Following a general process of interpretive grounded theory, we collected faculty members' perceptions and experiences related to their career development and advancement via in-depth semi structured-interviews of 23 faculty at a medical school in the United States. We analyzed the interview transcripts using thematic and constant-comparison analyses, informed by Bourdieu's theory of practice emphasizing the concepts of habitus, field, doxa, illusio, and capital.Findings: While there was a general perception of collaborative success in the school, access to resources seemed to be unequally distributed and linked to faculty positions. Career opportunities, such as leadership and promotion, were mostly granted by leaders based on interpersonal relationships (social capital). Clinical faculty's limited access to professional development activities (cultural capital), including research, limited their likelihood for promotion (symbolic capital) at the school. An institutional emphasis on clinical productivity reinforced clinical faculty's constraints on academic scholarship, which led to perceived inequities by clinical faculty. Participants also perceived subtle gender bias and an unequal distribution of power among the specialties, which contradicted a culture of collaboration and support in the school.Insights: Complex power structures influence faculty career success. Unequal access and differential power among faculty positions resulted in disparities in career advancement. Greater transparency, equity, and inclusivity are obvious suggestions for change to allow all faculty to benefit from essential resources and career building opportunities. Furthermore, building high-quality relationships between leaders and faculty and mutual respect between specialties are essential to sustaining an organizational culture conducive to career success for all faculty. Faculty will benefit from a greater awareness of the structural and normative aspects of a medical school that are less obvious and more difficult to change. This is the value of applying Bourdieu's theory of practice to the socio-cultural dynamics of the medical school.

Synergistic Effects of Limosilactobacillus fermentum ASBT-2 with Oxyresveratrol Isolated from Coconut Shell Waste.

Value-added phytochemicals from food by-products and waste materials have gained much interest and among them, dietary polyphenolic compounds with potential biological properties extend a promising sustainable approach. Oxyresveratrol (Oxy), a stilbenoid polyphenol, possesses great therapeutic potential, though its pharmacokinetic issues need attention. A good source of oxyresveratrol was found in underutilized coconut shells and the synbiotic applications of the compound in combination with a potential probiotic isolate Limosilactobacillus fermentum ASBT-2 was investigated. The compound showed lower inhibitory effects on the strain with minimum inhibitory concentration (MIC) of 1000 µg/mL. Oxyresveratrol at sub-MIC concentrations (500 µg/mL and 250 µg/mL) enhanced the probiotic properties without exerting any inhibitory effects on the strain. The combination at sub- MIC concentration of the compound inhibited Salmonella enterica and in silico approaches were employed to elucidate the possible mode of action of oxy on the pathogen. Thus, the combination could target pathogens in the gut without exerting negative impacts on growth of beneficial strains. This approach could be a novel perspective to address the poor pharmacokinetic properties of the compound.

Building Inclusive Work Environments.

A truly inclusive organization cultivates a sense of belonging and value in its members, realizing their contributions are vital to its success. Acknowledging and then dismantling exclusionary systems and policies are essential to creating environments grounded in diversity and equity. This process requires intentionality, accountability, and swift action on the part of leadership. Additionally, the role of organizational accountability, through tracking performance metrics, gauging employee satisfaction and engagement, and routinely assessing identified goals and objectives, is critical to sustaining inclusivity. In this article, we present a review of the literature and offers recommendations to build and sustain an inclusive environment.

Sequential dosing of convalescent COVID-19 plasma with significant temporal clinical improvements in a persistently SARS-COV-2 positive patient.

The current global pandemic, SARS-CoV-2 infection, is still extending across the world affecting millions of lives to the date. While new successful vaccines are available with promising outcomes to minimize the spread and to reduce the severity of the disease, optimal therapeutic options still remain elusive. COVID-19 convalescent plasma (CCP) is an investigational treatment option which studies suggesting signals of efficacy and favorable outcomes only for patients treated very early in course of the disease. Benefits of the use of CCP later in the disease remain highly debated and therefore are not common practice. We hereby report a case of severe SARS-CoV-2 infection in a young male patient with prolonged COVID-19 positivity who received repeat doses of CCP treatments later in the disease with temporal clinical improvement. This patient's case highlights the need of further studies evaluating efficacy of repeated dosing of CCP. This also suggests a potential of successful use of CCP later in the disease in selected COVID-19 patients.

Draft Genome Sequence of a Lactobacillus fermentum Strain Isolated from Domestic Sewage in Kerala, India.

We report the draft genome sequence of a putative probiotic strain, Lactobacillus fermentum ASBT-2, isolated from domestic sewage in Kerala, India. The strain showed probiotic properties (tolerance to low pH and bile salts, binding to host matrix) and reduced the coliform count by 90% in a biofilter used to treat wastewater.

Pulmonary mucormycosis associated with medical marijuana use.

A 66-year-old man with diabetes presented to the hospital with a two-month history of dyspnea, cough, rust-colored sputum, night sweats and 20 pound weight loss. He had begun smoking medical marijuana 3 months earlier. CT of the chest showed multiple bilateral large ground glass opacities with surrounding consolidation. Infectious workup was negative. BAL was non-diagnostic. He was treated with broad spectrum antibiotics without improvement. VATS was performed and cultured lung tissue grew Rhizopus species. He was started on intravenous liposomal amphotericin B and micafungin and then transitioned to oral posaconazole after two weeks. Repeat CT two months later showed stable size of the cavities. One month later he died of massive pulmonary hemorrhage. Here we document what we believe is the first known case of pulmonary mucormycosis associated with medical marijuana use.

Empyema Necessitans in the Setting of Methicillin-Susceptible Staphylococcus aureus Causing Pneumonia and Bacteremia.

Empyema necessitans (EN) is a rare phenomenon that refers to an insidious extension of the empyema through parietal pleura and subsequent dissection into subcutaneous tissue of the chest wall. A 29-year-old man presented to the hospital with fever and chills a few days after an inadvertent needle stick while injecting heroin. His left forearm was warm with an area of fluctuance. He underwent incision and drainage of the left forearm abscess with fluid submitted for Gram stain and culture. His condition rapidly deteriorated due to sepsis, and he required transfer to the intensive care unit. A new 4 × 3 cm area over the left pectoralis muscle had become increasingly indurated, fluctuant, and erythematous. CT of the chest demonstrated extensive cavitary lung lesions and a large loculated left-sided pleural effusion with extension through the chest wall. TEE revealed a 3 cm complex lesion on the superior septal leaflet of the tricuspid valve. The patient underwent incision and drainage of the pectoralis major EN with placement of a drain. Blood and sputum cultures grew methicillin-susceptible Staphylococcus aureus (MSSA) at which time antibiotic therapy was tailored to oxacillin. Our case highlights a rare occurrence of EN due to MSSA in a patient with intravenous drug use (IDU) and underscores the importance of prompt diagnosis and treatment.

Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment.

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Delayed Diagnosis of Tuberculous Arthritis of the Knee in an Air Force Service Member: Case Report and Review of the Literature.

Tuberculosis (TB) is a common disease worldwide affecting more than 2 billion people, including latent, pulmonary, and extrapulmonary TB. The presentation of disseminated TB is variable and dependent on the organs affected. Therefore, making the diagnosis and providing appropriate treatment can be delayed. We present a case of disseminated TB in a patient with Sjögren's syndrome on hydroxychloroquine monotherapy without traditional risk factors.

Histoplasmosis complicating tumor necrosis factor-α blocker therapy: a retrospective analysis of 98 cases.

BACKGROUND: Histoplasmosis may complicate tumor necrosis factor (TNF)-α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. METHODS: We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. RESULTS: The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06-14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03-1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1-69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. CONCLUSIONS: In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Histoplasmosis after solid organ transplant.

BACKGROUND: To improve our understanding of risk factors, management, diagnosis, and outcomes associated with histoplasmosis after solid organ transplant (SOT), we report a large series of histoplasmosis occurring after SOT. METHODS: All cases of histoplasmosis in SOT recipients diagnosed between 1 January 2003 and 31 December 2010 at 24 institutions were identified. Demographic, clinical, and laboratory data were collected. RESULTS: One hundred fifty-two cases were identified: kidney (51%), liver (16%), kidney/pancreas (14%), heart (9%), lung (5%), pancreas (2%), and other (2%). The median time from transplant to diagnosis was 27 months, but 34% were diagnosed in the first year after transplant. Twenty-eight percent of patients had severe disease (requiring intensive care unit admission); 81% had disseminated disease. Urine Histoplasma antigen detection was the most sensitive diagnostic method, positive in 132 of 142 patients (93%). An amphotericin formulation was administered initially to 73% of patients for a median duration of 2 weeks; step-down therapy with an azole was continued for a median duration of 12 months. Ten percent of patients died due to histoplasmosis with 72% of deaths occurring in the first month after diagnosis; older age and severe disease were risk factors for death from histoplasmosis. Relapse occurred in 6% of patients. CONCLUSIONS: Although late cases occur, the first year after SOT is the period of highest risk for histoplasmosis. In patients who survive the first month after diagnosis, treatment with an amphotericin formulation followed by an azole for 12 months is usually successful, with only rare relapse.

Visceral leishmaniasis with associated immune dysregulation leading to lymphoma.

OBJECTIVE: We describe an atypical presentation of visceral leishmaniasis (VL) complicated by Epstein-Barr virus (EBV)-lymphoproliferative disorder and angioimmunoblastic T-cell lymphoma in a U.S. Government contractor recently deployed to Iraq and Afghanistan. METHODS: We performed a search of PubMed (1966-2012) using the terms visceral, leishmaniasis, operation, iraqi, freedom, desert, storm, EBV, lymphoproliferative, angioimmunoblastic, and lymphoma. The purpose of the search was two-fold: to find reported cases of VL during U.S. military operations and to ascertain if lymphoproliferative disorder (specifically, because of EBV) was ever described as a sequelae of VL. RESULTS: Case series of VL acquired in the Middle East between 1990 and 2012 showed that while fever, abdominal pain, and hepatosplenomegaly were common signs and symptoms of VL, diffuse lymphadenopathy (our patient's presentation) was rare. Moreover, VL in and of itself lends to profound immune dysregulation, leading to a myriad of complications to include EBV-lymphoproliferative diseases. CONCLUSIONS: Diffuse lymphadenopathy because of VL is a very atypical presentation for infection acquired in the Middle East. Clinicians must be mindful of the extreme immune dysfunction that occurs as a result of this potentially fatal infection and the associated complications to include EBV-related lymphoproliferative disorders and lymphoma.

Pneumonia in military trainees: a comparison study based on adenovirus serotype 14 infection.

BACKGROUND: Adenovirus serotype 14 (Ad-14) recently emerged as a respiratory pathogen in the United States, with studies suggesting higher morbidity and mortality. This study was conducted to determine whether Ad-14 is associated with clinical outcomes in otherwise healthy patients with pneumonia. METHODS: Medical records of military trainees hospitalized with pneumonia during an outbreak of Ad-14 infection were reviewed. Clinical, radiographic, and laboratory parameters were compared on the basis of Ad-14 infection. RESULTS: Two hundred thirty-four trainees received a diagnosis of pneumonia, and 83(35%) were hospitalized. Sixty-one percent of patients with pneumonia were Ad-14 positive; 43% of patients with Ad-14 pneumonia were hospitalized (83% of female patients and 40% of male patients; P = .04), compared with 40% of patients with Ad-14 negative cases. Ad-14 infection was associated with higher admission temperature (38.3°C [interquartile range, (IQR) 37.7, 39.4] vs 37.3°C [IQR (36.7, 38.5)]; P < .01) and lower white blood cell count (8.3 × 1000 cells/µL [IQR, 5.7, 12.4] vs 13 × 1000 cells/µL [IQR, 7.5, 12.9]; P = .01), neutrophil count (6.7 × 1000 cells/µL [IQR, 2.8, 9.7] vs 9.7 × 1000 cells/µL [IQR, 5.6, 12.1]; P = .02), lymphocyte count (0.9 × 1000 cells/µL [IQR, 0.8, 1.1] vs 1.3 × 1000 cells/µL [IQR, 1, 1.9]; P = .001), and platelet count (210 × 1000 cells/µL [IQR, 145, 285] vs 261 × 1000 cells/µL [IQR, 238, 343]; P < .01). Ad-14 pneumonia was not associated with specific radiographic findings, pneumonia severity score, intensive care unit admission, longer hospitalization, or 30-day mortality. CONCLUSIONS: During an outbreak of Ad-14 infection, Ad-14 infection was not associated with excess overall morbidity or mortality. Ad-14 infection was associated with specific laboratory and clinical parameters and higher hospitalization rates in female trainees. These data provide new insight to the epidemiology of Ad-14 infection.

Community-associated methicillin-resistant Staphylococcus aureus mediastinitis.

Community-associated methicillin (meticillin)-resistant Staphylococcus aureus (CA-MRSA) continues to emerge as a cause of serious infections, chiefly of the skin and soft tissues. We present the first documented case of CA-MRSA mediastinitis in an adult. Blood and mediastinal isolates were characterized as CA-MRSA by pulsed-field gel electrophoresis and susceptibility testing.

Oral and parenteral therapeutic options for outpatient urinary infections caused by enterobacteriaceae producing CTX-M extended-spectrum beta-lactamases.

Effective therapeutic options are needed for community-onset urinary tract infections due to Escherichia coli strains that produce CTX-M extended-spectrum beta-lactamases. We examined 46 urinary isolates producing CTX-M against several oral or long-acting parenteral antimicrobial agents. Approximately 90% were susceptible to fosfomycin and to a combination of cefdinir plus amoxicillin-clavulanate. All were susceptible to ertapenem.

Adenovirus serotype 14 pneumonia at a basic military training site in the United States, spring 2007: a case series.

Adenovirus, a frequent cause of mild respiratory disease in military trainees, can result in severe manifestations when outbreaks are caused by novel viral strains for which there is little pre-existing immunity. Twenty-five basic military trainees (BMTs) were hospitalized with adenovirus pneumonia from April 1, 2007 through June 21, 2007. Clinical findings for 9 of these patients with PCR-confirmed adenovirus serotype 14 were studied retrospectively. The clinical picture was characterized by cough (88.9%) and sputum production (77.8%). All trainees were febrile. Laboratory results showed 88.9% had normal white blood cell (WBC) counts, 66.7% with high monocytes, and 55.6% with low lymphocytes on differential. All had lobar pneumonia radiographically. One patient required the intensive care unit (ICU) and later expired. In conclusion, among hospitalized patients with the combination of fever, productive cough, normal WBC, a differential showing high monocytes and low lymphocytes in an immunocompetent young adult with lobar pneumonia warrants a high level of suspicion for adenovirus 14 pneumonia.