Miracle-dz/UniFAR-FTUs huggingface dataset:
Age-related macular degeneration: current knowledge of zinc metalloproteinases involvement.

BACKGROUND Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. The disease is characterized by photoreceptor loss in the macula and reduced retinal pigment epithelium (RPE) function, associated with matrix degradation, cell proliferation, neovascularization and inflammation. Matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play a critical role in the physiology of extracellular membrane (ECM) turnover and, in turn, in ECM pathologies, such as AMD. A balance between the activities of MMPs and Tissue inhibitors of metalloproteinase (TIMPs) is crucial for the integrity of the ECM components; indeed, a dysregulation in the ratio of these factors produces profound changes in the ECM, including thickening and deposit formation, which eventually might lead to AMD development. OBJECTIVE This article reviews the relevance and impact of zinc metalloproteinases on the development of AMD and their roles as biomarkers and/or therapeutic targets. We illustrate some studies on several inhibitors of MMPs currently used to dissect physiological properties of MMPs. Moreover, all molecules or technologies used to control MMP and ADAM activity in AMD are analyzed. CONCLUSIONS This study underlines the changes in the activity of MMPs expressed by RPE cells, highlights the functions of already used MMPs inhibitors and consequently suggests their application as therapeutic agents for the treatment of AMD.
Associations Between Cannabis Use, Sexual Behavior, and STIs/HIV in a Cohort of Young Men Who Have Sex with Men.

BACKGROUND Among men who have sex with men (MSM) the relationship between sexually transmitted infections (STIs) and cannabis use is not well established. We assessed cannabis use, sexual behavior, and STIs including HIV in a diverse cohort of young MSM. METHODS In Los Angeles the mSTUDY cohort conducted visits every 6 months with 512 MSM between 2014 and 2017 collecting demographics, sexual behaviors, and reports of frequency of substance use. Each visit conducted testing for gonorrhea, chlamydia and syphilis via blood, urine, and pharyngeal and rectal swabs by PCR, HIV was assessed using rapid tests for HIV negatives and viral load for HIV positives. We analyzed the relationship between cannabis use, sexual behaviors and STIs/HIV across 1,535 visits. RESULTS Significantly fewer participants tested positive for STIs at visits when reporting the previous 6 months use of only cannabis (11.7%) compared to no drugs (16.3%) or other drugs (20.0%), (p=0.01). Fewer MSM reporting only cannabis use than no or other drug use had been incarcerated, had incarcerated partners, experienced interpersonal violence, and were HIV positive. In multivariable analyses visits with positive STIs were associated with other drug use (adjusted odds ratio (AOR) 1.69, 95% CI (1.03-2.78)) but not use of cannabis only or no drug use after controlling for age, HIV status, new sex partners, and number of sex partners. CONCLUSIONS When MSM reported using cannabis exclusively fewer STIs were detected and lower risk sexual engagements reported than when MSM reported no drug or other drug use.
Molecular Detection of Anaplasma phagocytophilum in Blood-Sucking Flies (Diptera: Tabanidae) in Poland

Abstract Anaplasma phagocytophilum is a pathogen of veterinary and medical importance. It is the causative agent of tick-borne fever (TBF) in ruminants (also known as bovine or ovine granulocytic anaplasmosis), and of human granulocytic anaplasmosis (HGA) in humans. In Europe, A. phagocytophilum is transmitted by Ixodes ricinus (Linnaeus 1758) ticks. The aim of this study was to confirm the presence of A. phagocytophilum DNA in bloodsucking flies belonging to the Tabanidae family using molecular methods. It represents the first detection of this pathogen in Haematopota pluvialis (Linnaeus 1758), Tabanus bromius (Linnaeus 1758), and Tabanus distinguendus (Verrall 1909) in Europe.
Black Mold Growth in Cryostats Used for Mohs Micrographic Surgery.

Examination of our patient’s histological sections suggest a colonization-type tumor given the adjacent melanoma in situ observed along the dermoepidermal junction and the confinement of melanocytic nests within basal cell carcinoma nests. Furthermore, the melanoma did not penetrate the basement membrane. This suggests that the patient could be treated according to in situmelanomaguidelines rather thanmeasuring the Breslow depth of the basal cell tumor nests in the dermis. However, given the few cases of melanomawithin basal cell carcinomas, some questions remain regarding the truemalignantpotential of these lesions and the extent of the surgical margins and imaging work-up that are necessary.Therefore, close clinical follow-up for patients with these rare tumors is warranted.
Protein kinase A inhibition induces EPAC-dependent acrosomal exocytosis in human sperm

To interact with the egg, the spermatozoon must undergo several biochemical and motility modifications in the female reproductive tract, collectively called capacitation. Only capacitated sperm can undergo acrosomal exocytosis, near or on the egg, a process that allows the sperm to penetrate and fertilize the egg. In the present study, we investigated the involvement of cyclic adenosine monophosphate (cAMP)-dependent processes on acrosomal exocytosis. Inhibition of protein kinase A (PKA) at the end of capacitation induced acrosomal exocytosis. This process is cAMP-dependent; however, the addition of relatively high concentration of the membrane-permeable 8-bromo-cAMP (8Br-cAMP, 0.1 mmol l−1) analog induced significant inhibition of the acrosomal exocytosis. The induction of acrosomal exocytosis by PKA inhibition was significantly inhibited by an exchange protein directly activated by cAMP (EPAC) ESI09 inhibitor. The EPAC selective substrate activated AE at relatively low concentrations (0.02–0.1 μmol l−1), whereas higher concentrations (>5 μmol l−1) were inhibitory to the AE induced by PKA inhibition. Inhibition of PKA revealed about 50% increase in intracellular cAMP levels, conditions under which EPAC can be activated to induce the AE. Induction of AE by activating the actin severing-protein, gelsolin, which causes F-actin dispersion, was inhibited by the EPAC inhibitor. The AE induced by PKA inhibition was mediated by phospholipase C activity but not by the Ca2+-channel, CatSper. Thus, inhibition of PKA at the end of the capacitation process induced EPAC/phospholipase C-dependent acrosomal exocytosis. EPAC mediates F-actin depolymerization and/or activation of effectors downstream to F-actin breakdown that lead to acrosomal exocytosis.
Cooling therapy upregulates protein C activation in heat stressed rats: An experimental study

Protein C (PC) pathway homeostasis is implicated in heat stress (HS). This study determines whether cooling could improve the PC pathway in HS. Fifty‐six anesthetized rats were warmed to achieve HS (rectal temperature [Tr] 42°C). These rats were divided into seven groups: (a) control group:sacrifice immediately 15 min after HS; (b) HS+I:sacrifice immediately after 15 min ice‐water treatment or (c) 3 hr after HS; (d) HS+C:sacrifice immediately after 15‐min cold‐water treatment or (e) 3 hr after HS; (f) HS: sacrifice immediately 15 min after HS or (g) 3 hr after HS. Plasma PC, activated protein C (APC), and soluble thrombomodulin (sTM) levels were tested at both time points. After cooling, Tr in the HS+I and HS+C groups significantly decreased, when compared with the HS group, and Tr was significantly lower in the HS+I group than in the HS+C group ( p < 0.05). Furthermore, sTM levels were highest in the HS group among the groups at both time points. Plasma PC and APC levels increased after HS. In the HS+I and HS+C groups, plasma APC levels and the APC/PC ratio significantly increased at both time points. The proportions were significantly higher in the HS+I group than in the HS+C group, and there was no significant increase in APC/PC ratio in the HS group. Cooling exerts an anticoagulant effect following HS by increasing APC levels. Ice‐water blanket therapy is more effective than cold‐water blanket therapy in increasing APC levels.
Salinity and Temperature Influence Growth and Pigment Production in the Marine-Derived Fungal Strain Talaromyces albobiverticillius 30548

Marine-derived fungi that inhabit severe changing environments have gained increasing interest for their ability to produce structurally unique natural products. Fungi belonging to the Talaromyces and the close Penicillium genera are among the most promising microbes for bioactive compound production, including colored metabolites. Coupling pigment producing capability with bioactive effectiveness would be a valuable challenge in some specific fields such as dyeing, cosmeceutical, or food industries. In this sense, Talaromyces albobiverticillius 30548, a red pigment producing strain, has been isolated from the marine environment of Reunion Island, Indian Ocean. In this research, we analyzed the effect of temperatures (21–27 °C) and salinity levels (0–9%) on fungal growth and pigment production. Maximum pigment yield was obtained in non-salted media, when cultured at 27 °C after 10 days of submerged fermentation in PDB. However, maximum dry biomass production was achieved at stressed condition with 9% sea salts concentrated media at the same temperature. The results indicate that salinity of the culture media positively influences the growth of the biomass. Inversely, pigment production decreases with increase in salinity over 6%. Color coordinates of secreted pigments were expressed in CIELAB color system. The hue angles (h°) ranged from red to yellow colors. This indicated that the color distribution of fungal pigments depends on the salinity in the culture media. This study emphasizes the impact of abiotic stress (salt and temperature) on the growth and metabolome of marine-derived fungal strains.
The real and virtual simulator of simplified workstation for cognitive function testing

Trenażery i symulatory bazujące na technikach rzeczywistości wirtualnej zyskują coraz większą popularność i są stosowane w coraz większym zakresie. Elastyczność i realistyczna symulacja to jedne z głównych zalet rzeczywistości wirtualnej sprawiające, że jest ona chętnie wykorzystywana do szkolenia pracowników. W artykule przedstawiono przykład szkoleniowego środowiska wirtualnego uproszczonego stanowiska pracy oraz symulator rzeczywisty, który został wykorzystany do przeprowadzenia badań w celu weryfikacji skuteczności szkolenia za pomocą technik rzeczywistości wirtualnej. SŁOWA KLUCZOWE: symulatory, rzeczywistość wirtualna, druk 3D
Prognostic evaluation of severity of acute pancreatitis: not as black as it is painted

Acute pancreatitis (AP) is a systemic disease involving acute inflammation of the pancreatic gland due to premature activation of pancreatic proenzymes and different degree of damage to the adjacent tissues and sometimes more distant organs. An increasing trend is observed with the incidence of AP approximately 72 cases/100,000 inhabitants per year (1).
Real Time Monitoring of a UV Light-Assisted Biofunctionalization Protocol Using a Nanophotonic Biosensor

A protocol for the covalent biofunctionalization of silicon-based biosensors using a UV light-induced thiol–ene coupling (TEC) reaction has been developed. This biofunctionalization approach has been used to immobilize half antibodies (hIgG), which have been obtained by means of a tris(2-carboxyethyl)phosphine (TCEP) reduction at the hinge region, to the surface of a vinyl-activated silicon-on-insulator (SOI) nanophotonic sensing chip. The response of the sensing structures within the nanophotonic chip was monitored in real time during the biofunctionalization process, which has allowed us to confirm that the bioconjugation of the thiol-terminated bioreceptors onto the vinyl-activated sensing surface is only initiated upon UV light photocatalysis.
The Impact of Pediatric Palliative Care Involvement in the Care of Critically Ill Patients without Complex Chronic Conditions.

Background: The impact of pediatric palliative care (PPC) is well established for children with chronic complex diseases. However, PPC likely also benefits previously healthy children with acute life-threatening conditions. Objective: To determine the incidence and impact of PPC for previously healthy patients who died in a pediatric hospital. Design: Retrospective chart review of all pediatric deaths over four years. Setting/Subjects: Patients were 0 to 25 years old, died during an inpatient stay at an academic pediatric hospital ≥48 hours after admission, and had no complex chronic conditions (CCCs) before admission. Measurements: One hundred sixty-seven patients met the eligibility criteria. Most died in intensive care settings (n = 149, 89%), and few (n = 34, 20%) received PPC consultations or services. Results: Patients who received PPC services were more likely to receive a multidisciplinary care conference than did patients without PPC support (70.5% vs. 39.9%; p = 0.001), which also occurred earlier for patients who received PPC services (seven days vs. two days before death; p = 0.04). Most patients had documented end-of-life planning in their medical records; however, this occurred earlier for patients who received PPC consultation (9.5 days before death) than for those who did not (two days before death; p < 0.0001). Patients receiving PPC support (67.7%) were also more likely to have a do-not-resuscitate/intubate order before death than those who did not (39.9%; p = 0.004). Conclusions: Pediatric patients without known CCCs who subsequently die as inpatients benefit from PPC in terms of goals of care discussions and documentation of end-of-life care preferences.
Modern‐Day Nationwide Utilization of Intravascular Ultrasound and Its Impact on the Outcomes of Percutaneous Coronary Intervention With Coronary Atherectomy in the United States

Intravascular ultrasonography (IVUS) and coronary atherectomy (CA) are useful modalities in managing calcified coronary lesions. Considering an inadequacy of data, we aimed to compare the outcomes with versus without IVUS assistance in percutaneous coronary interventions (PCIs) with CA.
Genetic Hearing Loss and Gene Therapy

Genetic hearing loss crosses almost all the categories of hearing loss which includes the following: conductive, sensory, and neural; syndromic and nonsyndromic; congenital, progressive, and adult onset; high-frequency, low-frequency, or mixed frequency; mild or profound; and recessive, dominant, or sex-linked. Genes play a role in almost half of all cases of hearing loss but effective treatment options are very limited. Genetic hearing loss is considered to be extremely genetically heterogeneous. The advancements in genomics have been instrumental to the identification of more than 6,000 causative variants in more than 150 genes causing hearing loss. Identification of genes for hearing impairment provides an increased insight into the normal development and function of cells in the auditory system. These defective genes will ultimately be important therapeutic targets. However, the auditory system is extremely complex which requires tremendous advances in gene therapy including gene vectors, routes of administration, and therapeutic approaches. This review summarizes and discusses recent advances in elucidating the genomics of genetic hearing loss and technologies aimed at developing a gene therapy that may become a treatment option for in the near future.
Beyond entertainment. Dinamiche culturali all’origine della gamification | Beyond entertainment. Cultural developments at the root of the gamification

Il fenomeno della gamification ha generato negli anni un complesso dibattito, caratterizzato pero da posizioni divergenti, moltiplicazione di definizioni e giudizi contrastanti. In particolare, non sembra esserci convergenza su una definizione di gamification e sulle principali dinamiche che intercorrono tra la sfera del gioco e della societa. Scopo di questo articolo e approntare una risposta preliminare a tali problematiche attraverso gli strumenti della semiotica della cultura: nello specifico, analizzando e ricostruendo i processi storici, culturali e sociali che hanno contribuito alla nascita del concetto di gamification, a partire da una panoramica dei discorsi e delle interpretazioni storiche che hanno retto il concetto di gioco, i suoi limiti, valori e funzioni.
Stellenwert der Psychoonkologie in der Urologie

Zusammenfassung Nationale und internationale Behandlungsleitlinien und Zertifizierungskriterien für Krebszentren schließen psychoonkologische Mitbetreuung von belasteten Patienten heute zwingend ein; das gilt selbstverständlich auch für die Uro-Onkologie. Die systematische Feststellung der individuellen Unterstützungsbedürftigkeit in der Praxis soll durch „distress screenings“ bewerkstelligt werden. Während im Allgemeinen von ca. 30 % belasteter Krebspatienten ausgegangen wird (Anteil Patienten mit hohem distress oder psychischer Komorbidität), liegt die Rate bei der größten urologischen Entität, den Prostatakrebspatienten, niedriger (bei ca. 20 %). Der Zugang zu den indizierten Psychotherapien ist für viele Patienten aus persönlichen Gründen schwierig und führt zu relativ hohen Ablehnungsquoten − trotz hoher Belastung. Dies gilt insbesondere für die Uro-Onkologie. Ein entscheidender Faktor ist die Tatsache, dass hier überwiegend ältere Männer betroffen sind, ein Personenkreis, der sich generell schwer tut, eigene Emotionen wahrzunehmen, zu kommunizieren und psychologische Unterstützung in Anspruch zu nehmen. In diesem Zusammenhang werden hohe Anforderungen an die kommunikative Kompetenz des Urologen gestellt.
The effects of pro- and anti-atherosclerotic factors on intracellular nucleotide concentration in murine endothelial cells

Abstract Endothelial cell activation and dysfunction could lead to endothelial injury that is an important factor in the development of vascular diseases. Vascular injury is strongly associated with disturbed endothelial cell energetics and pyridine nucleotide pool. This study aimed to evaluate the effects of inflammatory stimuli (IL-6, LPS), uric acid, hyperglycemia, fatty acids, flavonoids, statins and nonsteroidal anti-inflammatory drugs on cellular concentration of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and nicotinamide adenine dinucleotide (NAD+) in cultured endothelial cells. Murine-immortalized heart endothelial cells (H5V cells) were treated with different concentrations of pro- and anti-atherosclerotic factors and intracellular concentration of nucleotides were measured using high performance liquid chromatography. Intracellular ATP concentration in H5V cells was not changed by inflammatory stimuli (IL-6 and LPS), uric acid, glucose, atorvastatin, acetylsalicylic acid, monounsaturated and polyunsaturated fatty acids. Only high concentration of palmitic acid (1 mM) and kaempferol (>0.1 mM) decreased intracellular ATP concentration. The concentration of intracellular ADP has not been altered by any of tested compounds. In turn, intracellular NAD+ pool was modified only by polyunsaturated fatty acids and atorvastatin. Linoleic acid, docosahexaenoic acid and atorvastatin increased cellular NAD+ concentration. Tested compounds have a small influence on murine endothelial cell energetics, but polyunsaturated fatty acids and atorvastatin increased intracellular NAD+ concentration that could be an important protective mechanism against endothelial cell injury.
Infection and Predictors of Outcome of Cirrhotic Patients after Emergency Care Hospital Admission.

INTRODUCTION AND AIMS We aimed to explore the impact of infection diagnosed upon admission and of other clinical baseline parameters on mortality of cirrhotic patients with emergency admissions. MATERIAL AND METHODS We performed a prospective observational monocentric study in a tertiary care center. The association of clinical parameters and established scoring systems with short-term mortality up to 90 days was assessed by univariate and multivariable Cox regression analysis. Akaike's Information Criterion (AIC) was used for automated variable selection. Statistical interaction effects with infection were also taken into account. RESULTS 218 patients were included. 71.2% were male, mean age was 61.1 ± 10.5 years. Mean MELD score was 16.2 ± 6.5, CLIF-consortium Acute on Chronic Liver Failure-score was 34 ± 11. At 28, 90 and 365 days, 9.6%, 26.0% and 40.6% of patients had died, respectively. In multivariable analysis, respiratory organ failure [Hazard Ratio (HR) = 0.15], albumin substitution (HR = 2.48), non-HCC-malignancy (HR = 4.93), CLIF-C-ACLF (HR = 1.10), HCC (HR = 3.70) and first episode of ascites (HR = 0.11) were significantly associated with 90-day mortality. Patients with infection had a significantly higher 90-day mortality (36.3 vs. 20.1%, p = 0.007). Cultures were positive in 32 patients with resistance to cephalosporins or quinolones in 10, to ampicillin/sulbactam in 14 and carbapenems in 6 patients. CONCLUSION Infection is common in cirrhotic ED admissions and increases mortality. The proportion of resistant microorganisms is high. The predictive capacity of established scoring systems in this setting was low to moderate.
Considering Type 1 Diabetes as a Form of Accelerated Muscle Aging

Recent evidence reveals impairments to skeletal muscle health in adolescent/young adults with type 1 diabetes (T1D). Interestingly, the observed changes in T1D are not unlike aged muscle, particularly, the alterations to mitochondria. Thus, we put forth the novel hypothesis that T1D may be considered a condition of accelerated muscle aging and that, similar to aging, mitochondrial dysfunction is a primary contributor to this complication.
Hindemith's voices

Paul Hindemith’s two–volume work on counterpoint is the summation of years of thinking about the subject and of teaching it. The volume on two-­part counterpoint is widely available as Vol. II of Unterweisung im Tonsatz, translated as The craft of musical composition Book II. Beyond this, the picture for the English reader becomes more complicated. The work on three­‐part counterpoint (Unterweisung Vol III: Ubungsbuch fur den dreistimmigen Satz) is still available only in German. Despite the volume’s bulk and detail, Hindemith was never completely happy with it, and it was published only after his death.