Identifying Putative Biomarkers of Foodborne Pathogens Using a Metabolomic Approach.

Metabolomics is the study of low molecular weight biochemical molecules (typically <1500 Da) in a defined biological organism or system. In case of food systems, the term "food metabolomics" is often used. Food metabolomics has been widely explored and applied in various fields including food analysis, food intake, food traceability, and food safety. Food safety applications focusing on the identification of pathogen-specific biomarkers have been promising. This chapter describes a nontargeted metabolite profiling workflow using gas chromatography coupled with mass spectrometry (GC-MS) for characterizing three globally important foodborne pathogens, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica, from selective enrichment liquid culture media. The workflow involves a detailed description of food spiking experiments followed by procedures for the extraction of polar metabolites from media, the analysis of the extracts using GC-MS, and finally chemometric data analysis using univariate and multivariate statistical tools to identify potential pathogen-specific biomarkers.

Outcomes of arthroscopic coracoclavicular management for acromioclavicular joint injuries: A systematic review.

Introduction: Various surgical procedures for coracoclavicular (CC) ligament repair have been described for symptomatic acromioclavicular joint dislocations, with none emerging as a clear gold standard. There has been increased interest in arthroscopic approaches. This systematic review evaluates clinical outcomes after arthroscopic surgeries used to treat chronic and acute AC joint dislocations. Methods: We searched three databases (PubMed, EMBASE, and OVID [MEDLINE]) from database inception to December 20, 2022. Studies were included if they met the following criteria: studies evaluating humans, English language studies, level of evidence I to IV, and studies investigating clinical outcomes in patients following arthroscopic surgery for coracoclavicular ligament reconstruction. Studies on open reconstruction techniques only were excluded. Primary outcomes included function/pain scores, coracoclavicular distances, complications, and revision rates. Results: Fifty-two studies were included. In 33 studies, postoperative Constant-Murley scores ranged from 82.8 to 99 points. Postoperative VAS scores ranged from 0.3 to 4.1 in 16 studies. In 46 studies, revision rates ranged from 0 % to 44.4 %. We did not observe a difference in revision rates between chronic and acute cases (P = 0.268). Complications were more common in chronic than acute cases (25.5 % vs. 16.4 %; P < 0.001). Conclusions: Arthroscopic surgery for chronic and acute CC ligament injuries exceeds the MCID and PASS for several outcomes, with low failure rates. Arthroscopic CC reconstruction is a safe and effective alternative for chronic AC joint dislocations. Level of evidence: IV (Systematic Review of Level I-IV Studies).

Deep Learning Model of Diastolic Dysfunction Risk Stratifies the Progression of Early-Stage Aortic Stenosis.

BACKGROUND: The development and progression of aortic stenosis (AS) from aortic valve (AV) sclerosis is highly variable and difficult to predict. OBJECTIVES: The authors investigated whether a previously validated echocardiography-based deep learning (DL) model assessing diastolic dysfunction (DD) could identify the latent risk associated with the development and progression of AS. METHODS: The authors evaluated 898 participants with AV sclerosis from the ARIC (Atherosclerosis Risk In Communities) cohort study and associated the DL-predicted probability of DD with 2 endpoints: 1) the new diagnosis of AS; and 2) the composite of subsequent mortality or AV interventions. Validation was performed in 2 additional cohorts: 1) in 50 patients with mild-to-moderate AS undergoing cardiac magnetic resonance (CMR) imaging and serial echocardiographic assessments; and 2) in 18 patients with AV sclerosis undergoing 18F-sodium fluoride (NaF) and 18F-fluorodeoxyglucose positron emission tomography (PET) combined with computed tomography (CT) to assess valvular inflammation and calcification. RESULTS: In the ARIC cohort, a higher DL-predicted probability of DD was associated with the development of AS (adjusted HR: 3.482 [95% CI: 2.061-5.884]; P < 0.001) and subsequent mortality or AV interventions (adjusted HR: 7.033 [95% CI: 3.036-16.290]; P < 0.001). The multivariable Cox model (incorporating the DL-predicted probability of DD) derived from the ARIC cohort efficiently predicted the progression of AS (C-index: 0.798 [95% CI: 0.648-0.948]) in the CMR cohort. Moreover, the predictions of this multivariable Cox model correlated positively with valvular 18F-NaF mean standardized uptake values in the PET/CT cohort (r = 0.62; P = 0.008). CONCLUSIONS: Assessment of DD using DL can stratify the latent risk associated with the progression of early-stage AS.

Exploring Hydrogel Nanoparticle Systems for Enhanced Ocular Drug Delivery.

Drug delivery to the ocular system is affected by anatomical factors like the corneal epithelium, blinking reflex, aqueous blood barrier, and retinal blood barrier, which lead to quick removal from the site and inefficient drug delivery. Developing a drug delivery mechanism that targets specific eye tissue is a major hurdle for researchers. Our study examines the challenges of drug absorption in these pathways. Hydrogels have been researched as a suitable delivery method to overcome some obstacles. These are developed alone or in conjunction with other technologies, such as nanoparticles. Many polymer hydrogel nanoparticle systems utilizing both natural and synthetic polymers have been created and investigated; each has pros and cons. The complex release mechanism of encapsulated agents from hydrogel nanoparticles depends on three key factors: hydrogel matrix swelling, drug-matrix chemical interactions, and drug diffusion. This mechanism exists regardless of the type of polymer. This study provides an overview of the classification of hydrogels, release mechanisms, and the role of controlled release systems in pharmaceutical applications. Additionally, it highlights the integration of nanotechnology in ocular disease therapy, focusing on different types of nanoparticles, including nanosuspensions, nanoemulsions, and pharmaceutical nanoparticles. Finally, the review discusses current commercial formulations for ocular drug delivery and recent advancements in non-invasive techniques. The objective is to present a comprehensive overview of the possibilities for enhancing ocular medication delivery through hydrogel nanoparticle systems.

The role of maximal inspiratory pressure on functional performance in adults with heart failure.

BACKGROUND: Exercise intolerance is common among adults with heart failure (HF) and is a strong prognostic indicator. We examined maximal inspiratory pressure (MIP) as an indicator of maximal and submaximal exercise capacity in older HF patients. METHODS: Fifty-one patients age ≥ 50 years with HF underwent MIP testing via the PrO2 device. Peak oxygen uptake (VO2), 6 min walk distance (6MWD), 30 s sit-to-stand test (STS), gait speed (GS), grip strength and lower extremity muscle strength [one-repetition maximum (1RM)] were measured. Correlation and exploratory multiple regression analyses investigated relationships between MIP, left ventricular ejection fraction (LVEF), age, body mass index (BMI) and physical function. MIP was then stratified by median (64 cm H2O), and endpoints were compared between median groups. RESULTS: The median age was 69 years [interquartile range (IQR): 66-73], and the median LVEF was 36.5% (IQR: 30%-45%). Regression identified MIP as an independent predictor for grip strength, 6MWD, 1RM weight and 30 s STS after adjustment for age, BMI and LVEF. MIP greater than the median (n = 25) independently predicted and reflected greater peak VO2 [14.2 (12.8-18.1) vs. 11.5 (9.7-13.0) mL/kg/min; P = 0.0007] as well as 6MWD, 1RM, 30 s STS and GS (all P < 0.05). CONCLUSION: The analysis demonstrates that MIP is a novel biometric for exercise tolerance in adults with HF. Assessments of MIP are safe and convenient, with the potential to enhance routine HF surveillance and provide novel biometrics to guide HF therapeutics.

Real-World Observational Analysis of Clinical Characteristics and Treatment Patterns of Patients with Chronic Sialorrhea.

Chronic sialorrhea is a condition characterized by excessive drooling, often associated with neurological and neuromuscular disorders such as Parkinson's disease, cerebral palsy, and stroke. Despite its prevalence, it remains underdiagnosed and poorly understood, leading to a lack of comprehensive data on patient demographics, clinical characteristics, and treatment patterns. This study aimed to help fill these existing gaps by analyzing real-world data using Optum's de-identified Clinformatics® Data Mart Database. Patients were required to have a diagnosis indicative of sialorrhea plus evidence of sialorrhea treatment between 1/1/2007 and 5/31/2022. Two cohorts were analyzed: patients with evidence of newly diagnosed sialorrhea and associated treatment, and sialorrhea patients initiating incobotulinumtoxinA. Clinical characteristics, comorbidities, symptoms, and treatment utilization were described before and after diagnosis and incobotulinumtoxinA initiation. No formal statistical comparisons were performed. Patients were predominantly aged 65 or older, male, and non-Hispanic white. Parkinson's disease and cerebral palsy were the most common comorbidities among adults and children, respectively. Treatment patterns suggest that anticholinergics are more commonly used than botulinum toxin therapy. The findings offer valuable information for improving diagnosis and treatment approaches and suggest a need for further research into treatment effectiveness, safety, and disease burden.

Rhombencephalosynapsis: A Rare Hindbrain Malformation.

Rhombencephalosynapsis (RES) is a rare condition found in the pediatric population. It occurs due to a fundamental failure of vermian differentiation caused by faulty gene expression in the earliest patterning areas of the brain between days 28 and 41 of gestation, resulting in a fused cerebellum. This report aims to discuss cases of this rare hindbrain malformation, identify its features on MRI, diagnose any associated anomalies, classify it based on severity, and study its syndromic associations. We report two rare cases of RES in patients presenting with complaints of ataxia, global motor developmental delay, hypotonia, and dysarthria, who underwent an MRI of the brain.

A Rare Case of Renal Angiomyolipoma and Polycystic Kidney Disease in a Patient with Tuberous Sclerosis.

Renal angiomyolipoma (AML) is a rare benign tumor that follows an autosomal dominant inheritance pattern. Its association with polycystic kidney disease is uncommon, with only a handful of cases documented in the literature. The growth of lesions to a significant size may lead to life-threatening complications. We report a case of a 32-year-old female who presented with a palpable mass and bilateral flank pain. Following clinical assessment and CT examination, the patient underwent a left radical nephrectomy. The resected mass measured 9.3 x 8.2 x 7.5 cm, and the subsequent histopathological examination confirmed the diagnosis as renal AML.

Scalp microbiome: a guide to better understanding scalp diseases and treatments.

The scalp microbiome represents an array of microorganisms important in maintaining scalp homeostasis and mediating inflammation. Scalp microbial dysregulation has been implicated in dermatologic conditions including alopecia areata (AA), dandruff/seborrheic dermatitis (D/SD), scalp psoriasis (SP) and folliculitis decalvans (FD). Understanding the impact of scalp microbial dysbiosis gives insight on disease pathophysiology and guides therapeutic decision making. Herein we review the scalp microbiome and its functional role in scalp conditions by analysis of metagenomic medical literature in alopecia, D/SD, SP, and other dermatologic disease.Increased abundance of Malassezia, Staphylococcus, and Brevibacterium was associated with SD compared to healthy controls. A higher proportion of Corynebacterium, actinobacteria, and firmicutes are present in AA patients, and lower proportions of Staphylococcus caprae are associated with worse clinical outcomes. Decreased prevalence of actinobacteria and Propionibacterium and increased firmicutes, staphylococcus, and streptococcus are associated with scalp psoriasis. Studies of central centrifugal cicatricial alopecia (CCCA) suggest scalp microbial composition contributes to CCCA's pro-inflammatory status. The most common organisms associated with FD include methicillin-resistant S. aureus and S. lugdunensis. Antifungals have been a mainstay treatment for these diseases, while other alternatives including coconut oils and shampoos with heat-killed probiotics have shown considerable potential efficacy by replenishing the scalp microbiome.

Innovative approaches to wound healing: insights into interactive dressings and future directions.

The objective of this review is to provide an up-to-date and all-encompassing account of the recent advancements in the domain of interactive wound dressings. Considering the gap between the achieved and desired clinical outcomes with currently available or under-study wound healing therapies, newer more specific options based on the wound type and healing phase are reviewed. Starting from the comprehensive description of the wound healing process, a detailed classification of wound dressings is presented. Subsequently, we present an elaborate and significant discussion describing interactive (unconventional) wound dressings. Latter includes biopolymer-based, bioactive-containing and biosensor-based smart dressings, which are discussed in separate sections together with their applications and limitations. Moreover, recent (2-5 years) clinical trials, patents on unconventional dressings, marketed products, and other information on advanced wound care designs and techniques are discussed. Subsequently, the future research direction is highlighted, describing peptides, proteins, and human amniotic membranes as potential wound dressings. Finally, we conclude that this field needs further development and offers scope for integrating information on the healing process with newer technologies.

Central nervous system active medication use in Medicare enrollees receiving home health care: association with chronic pain and anxiety level.

ABSTRACT: No comparative effectiveness data exist on nonopioid analgesics and nonbenzodiazepine anxiolytics to treat pain with anxiety. We examined the relationship between drug class and central nervous system (CNS) active drug polypharmacy on pain and anxiety levels in Medicare enrollees receiving home health (HH) care. This retrospective cohort study included enrollees with diagnoses and 2+ assessments of pain and anxiety between HH admission and discharge. Three sets of linear regression difference-in-reduction analyses assessed the association of pain or anxiety reduction with number of drugs; drug type; and drug combinations in those with daily pain and daily anxiety. Logistic regression analysis assessed the effect of medication number and class on less-than-daily pain or anxiety at HH discharge. A sensitivity analysis using multinomial regression was conducted with a three-level improvement to further determine clinical significance. Of 85,403 HH patients, 43% received opioids, 27% benzodiazepines, 26% gabapentinoids, 32% selective serotonin reuptake inhibitors, and 8% serotonin and norepinephrine reuptake inhibitors (SNRI). Furthermore, 75% had depression, 40% had substance use disorder diagnoses, and 6.9% had PTSD diagnoses. At HH admission, 83%, 35%, and 30% of patients reported daily pain, daily anxiety, and both, respectively. Central nervous system polypharmacy was associated with worse pain control and had no significant effect on anxiety. For patients with daily pain plus anxiety, pain was best reduced with one medication or any drug combination without opioid/benzodiazepine; anxiety was best reduced with combinations other than opiate/benzodiazepine. Gabapentinoids or SNRI achieved clinically meaningful pain control. Selective serotonin reuptake inhibitors provided clinically meaningful anxiety relief.

Adapting with the Pandemic: Modified Mohs Micrographic Surgery Using Rim and Deep Margin Technique.

The COVID-19 pandemic has changed many facets of medical care and has resulted in a rise in delayed treatments across all specialties, including cosmetic dermatology. Delayed care for squamous cell carcinomas (SCC) and basal cell carcinoma (BCC) is not only a burden for medical providers, but also confers a risk to patients, as delayed surgeries are associated with increased metastatic risk and tumor size. Mohs micrographic surgery (MMS) delayed by more than one year leads to increased risk of complications, including bleeding and impaired wound healing, especially in the elderly population. To decrease bleeding risks, we have developed a modified MMS technique known as the "rim and deep margin" technique. Here, we present additional cases using this technique to minimize bleeding and operative time for patients with an increased risk of morbidity. This technique has been used successfully in the past for large tumors and can now be used for patients who have faced delay of care, as evidenced by its success during the COVID-19 pandemic.

In situ gelling systems for ocular drug delivery.

In situ gelling systems represent a burgeoning paradigm in ocular drug administration, addressing intrinsic challenges posed by extant ocular formulations, such as compromised bioavailability and constraints in traversing the corneal barrier. This systematic review endeavours to comprehensively examine the contemporary landscape of research in this domain, focusing on the nuanced capabilities of in situ gelling systems to optimize drug delivery and enhance therapeutic outcomes, without much technological complexity. Employing a meticulous search strategy across diverse databases for publications and patents spanning the years 2015 to 2023 a total of 26 research papers and 14 patents meeting stringent inclusion criteria were identified. Synthesizing the collective insights derived from these investigations, it becomes evident that in situ gelling systems confer an ability to protract the residence time of formulations or active pharmaceutical ingredients (APIs) within the ocular milieu. This sustained presence engenders extended drug release kinetics, thereby fostering improved patient compliance and mitigating the proclivity for side effects attendant to frequent dosing. These salutary effects extend to diminished systemic drug absorption, augmented ocular bioavailability, and the prospect of reduced dosing frequencies, thereby amplifying patient adherence to therapeutic regimens. Intriguingly, the protective attributes of in situ gelling systems extend to the establishment of an ocular surface barrier, thereby abating the susceptibility to infections and inflammatory responses. In summation, this review underscores the auspicious potential of in situ gelling systems as a transformative approach to advancing ocular drug delivery, warranting sustained research endeavours and developmental initiatives for the betterment of global patient outcomes.

Artificial Intelligence in Dermatology: A Systematic Review of Its Applications in Melanoma and Keratinocyte Carcinoma Diagnosis.

BACKGROUND: Limited access to dermatologic care may pose an obstacle to the early detection and intervention of cutaneous malignancies. The role of artificial intelligence (AI) in skin cancer diagnosis may alleviate potential care gaps. OBJECTIVE: The aim of this systematic review was to offer an in-depth exploration of published AI algorithms trained on dermoscopic and macroscopic clinical images for the diagnosis of melanoma, basal cell carcinoma, and cutaneous squamous cell carcinoma (cSCC). METHODS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted on peer-reviewed articles published between January 1, 2000, and January 26, 2023. RESULTS AND DISCUSSION: Among the 232 studies in this review, the overall accuracy, sensitivity, and specificity of AI for tumor detection averaged 90%, 87%, and 91%, respectively. Model performance improved with time. Despite seemingly impressive performance, the paucity of external validation and limited representation of cSCC and skin of color in the data sets limits the generalizability of the current models. In addition, dermatologists coauthored only 12.9% of all studies included in the review. Moving forward, it is imperative to prioritize robustness in data reporting, inclusivity in data collection, and interdisciplinary collaboration to ensure the development of equitable and effective AI tools.

Jet-injection assisted photodynamic therapy for superficial and nodular basal cell carcinoma: A pilot study.

BACKGROUND: Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution. METHODS: For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale. RESULTS: Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5 (interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination. CONCLUSIONS: Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT.

Extramammary Paget disease. Part I. epidemiology, pathogenesis, clinical features, and diagnosis.

Extramammary Paget disease (EMPD) is a rare skin cancer of apocrine-rich skin that mimics common inflammatory and infectious dermatoses, leading to delays in diagnosis and increased patient morbidity. Better clinical recognition of this entity, multidisciplinary patient assessment, and deeper understanding of the underlying pathophysiology are essential to improve patient care and disease outcomes. It is important to distinguish primary intraepithelial/micro-invasive EMPD from invasive EMPD or cases with adenocarcinoma arising within EMPD. This 2-part continuing medical education series provides a complete picture of EMPD. Part 1 of this continuing medical education series reviews the epidemiology, oncogenesis, clinical and histopathologic presentation, workup, and prognosis of this rare cancer.