Resveratrol: Its Path from Isolation to Therapeutic Action in Eye Diseases.

Due to the confirmed therapeutic potential of resveratrol (Rv) for eye diseases, namely its powerful anti-angiogenic and antioxidant effects, this molecule must be studied more deeply. Nowadays, the pharmaceutic and pharmacokinetic available studies offer a troubling picture because of its low stability and bioavailability. To overcome this problem, researchers started to design and create different delivery systems that could improve the delivery amount of Rv. Therefore, this review aims to shed light on the proper and efficient techniques to isolate, purify and quantify the Rv molecule, and how this therapeutic molecule can be a part of a delivery system. The Rv great impact on aspects regarding its stability, bioavailability and absorption are also debated here, based on the existent literature on in vitro and in vivo human and animal studies. Moreover, after its absorption the Rv influence at the molecular level in ocular pathologies is described. In addition, the present review summarizes the available literature about Rv, hoping that Rv will gain more attention to investigate its unexplored side.

Low secondary attack rate after prolonged exposure to sputum smear positive miliary tuberculosis in a neonatal unit.

BACKGROUND: Several neonatal intensive care units (NICU) have reported exposure to sputum smear positive tuberculosis (TB). NICE guidelines give support regarding investigation and treatment intervention, but not for contact definitions. Data regarding the reliability of any interferon gamma release assay (IGRA) in infants as a screening test for TB infection is scarce. We report an investigation and management strategy and evaluated the viability of IGRA (T-Spot) in infants and its concordance to the tuberculin skin test (TST). METHODS: We performed an outbreak investigation of incident TB infection in a NICU after prolonged exposure to sputum smear positive miliary TB by an infant's mother. We defined individual contact definitions and interventions and assessed secondary attack rates. In addition, we evaluated the technical performance of T-Spot in infants and compared the results with the TST at baseline investigation. RESULTS: Overall, 72 of 90 (80%) exposed infants were investigated at baseline, in 51 (56.7%) of 54 (60%) infants, follow-up TST at the age of 6 months was performed. No infant in our cohort showed a positive TST or T-Spot at baseline. All blood samples from infants except one responded to phytohemagglutinin (PHA), which was used as a positive control of the T-Spot, demonstrating that cells are viable and react upon stimulation. 149 of 160 (93.1%) exposed health care workers (HCW) were investigated. 1 HCW was tested positive, having no other reason than this exposure for latent TB infection. 5 of 92 (5.5%) exposed primary contacts were tested positive, all coming from countries with high TB incidences. In total, 1 of 342 exposed contacts was newly diagnosed with latent TB infection. The secondary attack rate in this study including pediatric and adult contacts was 0.29%. CONCLUSION: This investigation highlighted the low transmission rate of sputum smear positive miliary TB in a particularly highly susceptible population as infants. Our expert definitions and interventions proved to be helpful in terms of the feasibility of a thorough outbreak investigation. Furthermore, we demonstrated concordance of T-Spot and TST. Based on our findings, we assume that T-Spot could be considered a reliable investigation tool to rule out TB infection in infants.

Hybrid polymeric therapeutic microcarriers for thermoplasmonic-triggered release of resveratrol.

Diabetic retinopathy (DR) is a severe ocular complication that causes retinal damage, being one of the leading causes of blindness globally, thus the development of new strategies to prevent and treat DR as well as other degenerative diseases is highly desired. This work is focused on the design and fabrication of an ingenious model of polymeric microcapsules (MC) for controlled drug delivery in human retina cells able to carry therapeutic resveratrol (RSV) molecules in tandem with active anisotropic gold bipyramidal nanoparticles (AuBPs) as efficient photothermal agents. Specifically, MC were developed via a Layer-by-Layer deposition technique, by successively adding oppositely charged polyelectrolytes on a RSV-conjugated calcium carbonate (CaCO3) core. For the monitorization and localization of the as-formed spherical fluorescent MC inside human retina pigmented epithelial (RPE) D407 cells, fluorescein isothiocyanate, a Food and Drug Administration approved fluorophore, was attached between the polyelectrolytes layers. High-performance liquid chromatography analysis revealed a loading efficiency of over 90% of RSV on the CaCO3 core and demonstrates its release upon NIR irradiation as a consequence of the thermoplasmonic effect of MC. The cytotoxicity of the RSV-carrying MC inside human retina cells was assessed by WST-1 assay. Finally, cellular internalization and localization of the MC inside living RPE cells were monitored via Conventional Fluorescence and Re-Scanning Confocal Fluorescence Microscopy. This research seeks to take use of the novel MC and implement them as potential intraocular RSV delivery vehicles for the therapy of DR.

Spectrum of Large and Medium Vessel Vasculitis in Adults: Primary Vasculitides, Arthritides, Connective Tissue, and Fibroinflammatory Diseases.

PURPOSE OF REVIEW: To provide a comprehensive overview of the spectrum of large and medium vessel vasculitis in adults with primary vasculitides, arthritides, connective tissue, and fibroinflammatory diseases as well as vasculitis mimics, for an efficient differential diagnosis and initial diagnostic approach. RECENT FINDINGS: Imaging has had a tremendous impact on the diagnosis of medium to large vessel vasculitis, now often replacing histopathologic confirmation and identifying new disease manifestations (e.g., intracranial disease in giant cell arteritis; vascular manifestations of IgG4-related disease). Novel diseases or syndromes involving blood vessels have been described (e.g., VEXAS-Syndrome with polychondritis). The use of the terms "medium" or "large" vessel varies considerably between medical specialties. The differential diagnosis of large and medium vessel vasculitis is becoming increasingly complex as new entities or disease manifestations of known inflammatory rheumatic diseases are regularly identified. A more precise and widely recognized definition of the vessel sizes would make future research more comparable.

Spectrum of Large- and Medium-Vessel Vasculitis in Adults: Neoplastic, Infectious, Drug-Induced, Autoinflammatory, and Primary Immunodeficiency Diseases.

PURPOSE OF REVIEW: To provide a comprehensive review of drugs and neoplastic, infectious, autoinflammatory, and immunodeficiency diseases causing medium- to large-vessel vasculitis in adults with emphasis on information essential for the initial diagnostic process. RECENT FINDINGS: Entities with medium- to large-vessel vasculitis as clinical manifestations have been described recently (e.g., adenosine deaminase-2 deficiency, VEXAS-Syndrome), and vasculitis in established autoinflammatory or immunodeficiency diseases is increasingly being identified. In the diagnostic process of medium- to large-vessel vasculitis in adults, a large variety of rare diseases should be included in the differential diagnosis, especially if diagnosis is made without histologic confirmation and in younger patients. Although these disorders should be considered, they will undoubtedly remain rare in daily practice.

Anthocyanins as Key Phytochemicals Acting for the Prevention of Metabolic Diseases: An Overview.

Anthocyanins are water-soluble pigments present in fruits and vegetables, which render them an extensive range of colors. They have a wide distribution in the human diet, are innocuous, and, based on numerous studies, have supposed preventive and therapeutical benefits against chronic affections such as inflammatory, neurological, cardiovascular, digestive disorders, diabetes, and cancer, mostly due to their antioxidant action. Despite their great potential as pharmaceutical applications, they have a rather limited use because of their rather low stability to environmental variations. Their absorption was noticed to occur best in the stomach and small intestine, but the pH fluctuation of the digestive system impacts their rapid degradation. Urine excretion and tissue distribution also occur at low rates. The aim of this review is to highlight the chemical characteristics of anthocyanins and emphasize their weaknesses regarding bioavailability. It also targets to deliver an update on the recent advances in the involvement of anthocyanins in different pathologies with a focus on in vivo, in vitro, animal, and human clinical trials.

Deep infection with Mycobacterium marinum: successful treatment of a frequently misdiagnosed disease.

We report a rare yet typical presentation of a severe infection with Mycobacterium marinum that affected the deep structure of the hand and wrist of a 43-old fish breeder. A combination therapy of surgical debridement and antibiotic treatment with clarithromycin and ethambutol for 6 months led to a total resolution of the symptoms. Intensive rehabilitation completely restored the function of the hand.

The role of FDG PET/CT in therapy control of aortic graft infection.

PURPOSE: 18F-FDG PET/CT (PET/CT) is a useful tool for the diagnosis of aortic graft infection (AGI), but has rarely been used to influence therapeutic decisions during follow-up. We aimed to study the role of PET/CT in the long-term monitoring of patients. METHODS: Participants of the prospective Vascular Graft Infection Cohort Study (VASGRA) were included if they had microbiologically proven AGI. We quantified the metabolic activity in PET/CT by using maximum standardized uptake value (SUVmax) and further classified it as being focal or diffuse. Multivariable linear regression models were fit using generalized estimating equations to investigate factors associated with SUVmax over time. RESULTS: Sixty-eight participants with AGI contributed to 266 PET/CTs including 36 examinations performed after stop of antimicrobial therapy. Higher C-reactive protein (CRP) (adjusted coefficient per log10 mg/L 0.05 [95% C.I. 0.02-0.08]) was associated with higher SUVmax. CRP, metabolic and clinical findings informed the decision to either start (medians of SUVmax 7.1 and CRP 31.5 mg/L; 100% focal uptake), escalate (SUVmax 9.5; CRP 31.5; 100% focal uptake), continue (SUVmax 6.0; CRP 9.95 mg/L; 90% focal uptake), or stop (SUVmax 4.3; CRP 3.5 mg/L; 61% focal uptake) antibiotic treatment. Of note, decisions to escalate or continue antibiotic treatment were taken despite normal CRP values in 12.5 and 35.7% of PET/CTs, respectively. CONCLUSIONS: Consecutive PET/CTs could influence the clinical decision-making in patients with AGI in the near future. More studies on the use of PET/CT in case of aortic graft infection may offer the potential for individualized treatment approaches. CLINICALTRIALS. GOV IDENTIFIER: NCT01821664.

Is there a role for procalcitonin in differentiating uncomplicated and complicated diverticulitis in order to reduce antibiotic therapy? A prospective diagnostic cohort study.

AIMS OF THE STUDY: While studies show that antibiotic treatment for uncomplicated diverticulitis seems to have no benefit, most experts advocate antimicrobial therapy for complicated diverticulitis. However, even for uncomplicated diverticulitis, most clinicians are very reluctant to withhold antibiotics. Biomarkers could help to guide antibiotic therapy as this approach has been shown to be effective for acute respiratory infections. In this diagnostic cohort study we evaluated whether procalcitonin could be a biomarker to distinguish complicated from uncomplicated cases of diverticulitis. METHODS: Complicated diverticulitis was defined as having abscess formation or perforation diagnosed by abdominal computed tomography (CT) scan. In all patients with suspected diverticulitis, procalcitonin values were measured at admission and on day 2. These values were blinded for clinicians, and treatment was carried out according to the physician's judgement. Two groups (complicated vs uncomplicated diverticulitis) were defined. Patients who had received antibiotic treatment before admission were excluded. Difference in procalcitonin values was calculated for both groups using the Mann-Whitney test. Receiver operating characteristics (ROC) were calculated to determine cut-off values for procalcitonin according to the gold standard (abdominal CT scans). RESULTS: 115 patients were included for analysis. 35 patients (30%) suffered from complicated diverticulitis. The median procalcitonin value for uncomplicated diverticulitis was significantly lower compared to complicated diverticulitis (median 0.05, interquartile range [IQR] 0.05-0.06 ng/l vs median 0.13, IQR 0.05-0.23 ng/l; p <0.0001). In the ROC analysis, the sensitivity and specificity were 81% and 91% when the highest procalcitonin value (days 1 and 2) was considered, with a cut-off value of 0.1 ng/l. CONCLUSION: Procalcitonin was able to differentiate with a high sensitivity and specificity between complicated and uncomplicated cases of diverticulitis when combined with abdominal CT scans. As most clinicians still treat uncomplicated diverticulitis with antibiotics, procalcitonin could be an interesting parameter for guiding therapy and decreasing antibiotic usage. This should be further evaluated in randomised trials.

Paroxysmal kinesigenic dyskinesia-like phenotype in multiple sclerosis.

In April 2015, a 20-year-old woman with multiple sclerosis (MS) presented with acute onset of repetitive abnormal postures and choreatic movements of the right arm, precipitated by voluntary movements (online video 1 and 2). Brain magnetic resonance imaging (MRI) showed a new active MS lesion involving the basal ganglia on the left side (Figure 1(a)). Intravenous steroid treatment resulted in rapid regression of this paroxysmal kinesigenic dyskinesia (PKD)-like hyperkinetic movement disorder. The patient became asymptomatic within 3 months. PKD is characterized by recurrent uni- or bilateral choreoathetosis and usually represents an autosomal dominant inherited disorder caused by PRRT2 gene mutations. As in the present case, a PKD-like phenotype may be associated with MS relapses in presumably genetic negative cases.

Correction: A Cross-Sectional Study of Colonization Rates with Methicillin-Resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) and Carbapenemase-Producing Enterobacteriaceae in Four Swiss Refugee Centres.

[This corrects the article DOI: 10.1371/journal.pone.0170251.].

A Cross-Sectional Study of Colonization Rates with Methicillin-Resistant Staphylococcus aureus (MRSA) and Extended-Spectrum Beta-Lactamase (ESBL) and Carbapenemase-Producing Enterobacteriaceae in Four Swiss Refugee Centres.

BACKGROUND: The recent crisis of refugees seeking asylum in European countries challenges public health on many levels. Most refugees currently arrive from Syria, Afghanistan, or Eritrea. Data about multidrug resistant bacteria (MDR) prevalence are not present for these countries. However, when entering the European heath care systems, data about colonisation rates regarding highly resistant bacterial pathogens are important. METHODS: We performed a cross-sectional screening in four Swiss refugee centres to determine the colonization rates for MRSA and ESBL- and carbapenemase-producing Enterobacteriaceae. We used pharyngeal, nasal, and inguinal swabs for MRSA and rectal swabs and urine for ESBL and carbapenemase screening using standard microbiological procedures. Whole genome sequencing (WGS) was used to determine the relatedness of MRSA isolates with high resolution due to a suspected outbreak. RESULTS: 41/261(15.7%) refugees were colonized with MRSA. No differences regarding the country of origin were observed. However, in a single centre significantly more were colonized, which was confirmed to be a recent local outbreak. 57/241 (23.7%) refugees were colonized with ESBL with significantly higher colonisation in persons originating from the Middle East (35.1%, p<0.001). No carbapenemase producers were detected. CONCLUSION: The colonisation rate of the refugees was about 10 times higher for MRSA and 2-5 times higher for ESBL compared to the Swiss population. Contact precaution is warranted for these persons if they enter medical care. In cases of infections, MRSA and ESBL-producing Enterobacteriaceae should be considered regarding antibiotic treatment choices.