Irisin: An anti-inflammatory exerkine in aging and redox-mediated comorbidities.

Human beings lead largely sedentary lives. From an evolutionary perspective, such lifestyle is not beneficial to health. Exercise can promote many enabling pathways, particularly through circulating exerkines, to optimize individual health and quality of life. Such benefits might explain the protective effects of exercise against aging and noncommunicable diseases. Nevertheless, the miRNA-mediated molecular mechanisms and exerkine interorgan crosstalk that underlie the beneficial effects of exercise remain poorly understood. In this mini review, we focused on the exerkine, irisin, mainly produced by muscle contraction during adaptation to exercise and its beneficial effects on body homeostasis. Herein, the complex role of irisin in metabolism and inflammation is described, including its subsequent effects on thermogenesis through browning to control obesity and improve glycemic regulation for diabetes mellitus control, its potential to improve cognitive function (via brain derived neurotrophic factor), and its pathways of action and role in aging.

Predictive factors of revision endoscopic sinus surgery.

PURPOSE: Despite endoscopic sinus surgery (ESS) being the standard best treatment for chronic rhinosinusitis with nasal polyps (CRSwNP), there still remains a high recurrence rate of nasal polyps after ESS. The aim of this study was to analyze the impact of ESS in the treatment of CRSwNP and identify possible predictors for revision surgery. METHODS: We conducted a cross-sectional retrospective study of patients with CRSwNP submitted to ESS between the years 2013 and 2021. RESULTS: We analyzed 517 cases, of which 15.1% were submitted to revision ESS. The presence of hyposmia/anosmia, asthma, intolerance/allergy to non-steroid inflammatory drugs, non-steroidal anti-inflammatory drug exacerbated respiratory disease, and bilateral polyposis were more frequent in patients who needed revision surgery. Initial values of peripheral eosinophilia and Lund-Mackay scores were significantly higher in this sub-group of patients. Lund-Mackay score was the only independent risk factor for revision surgery. CONCLUSIONS: Factors like peripheral eosinophilia and Lund-Mackay score were associated with a higher probability of revision ESS. Applying these concepts to the clinical practice could help predict the evolution of patient's pathology in the post-operative period and identify in advance those cases that may need a multidisciplinary approach.

Biochemical and Behavioural Alterations Induced by Arsenic and Temperature in Hediste diversicolor of Different Growth Stages.

Contamination with Arsenic, a toxic metalloid, is increasing in the marine environment. Additionally, global warming can alter metalloids toxicity. Polychaetes are key species in marine environments. By mobilizing sediments, they play vital roles in nutrient and element (including contaminants) cycles. Most studies with marine invertebrates focus on the effects of metalloids on either adults or larvae. Here, we bring information on the effects of temperature increase and arsenic contamination on the polychaete Hediste diversicolor in different growth stages and water temperatures. Feeding activity and biochemical responses-cholinesterase activity, indicators of cell damage, antioxidant and biotransformation enzymes and metabolic capacity-were evaluated. Temperature rise combined with As imposed alterations on feeding activity and biochemical endpoints at different growth stages. Small organisms have their antioxidant enzymes increased, avoiding lipid damage. However, larger organisms are the most affected class due to the inhibition of superoxide dismutase, which results in protein damage. Oxidative damage was observed on smaller and larger organisms exposed to As and temperature of 21 °C, demonstrating higher sensibility to the combination of temperature rise and As. The observed alterations may have ecological consequences, affecting the cycle of nutrients, sediment oxygenation and the food chain that depends on the bioturbation of this polychaete.

Riluzole-Rasagiline Hybrids: Toward the Development of Multi-Target-Directed Ligands for Amyotrophic Lateral Sclerosis.

Polypharmacology is a new trend in amyotrophic lateral sclerosis (ALS) therapy and an effective way of addressing a multifactorial etiology involving excitotoxicity, mitochondrial dysfunction, oxidative stress, and microglial activation. Inspired by a reported clinical trial, we converted a riluzole (1)-rasagiline (2) combination into single-molecule multi-target-directed ligands. By a ligand-based approach, the highly structurally integrated hybrids 3-8 were designed and synthesized. Through a target- and phenotypic-based screening pipeline, we identified hit compound 6. It showed monoamine oxidase A (MAO-A) inhibitory activity (IC50 = 6.9 µM) rationalized by in silico studies as well as in vitro brain permeability. By using neuronal and non-neuronal cell models, including ALS-patient-derived cells, we disclosed for 6 a neuroprotective/neuroinflammatory profile similar to that of the parent compounds and their combination. Furthermore, the unexpected MAO inhibitory activity of 1 (IC50 = 8.7 µM) might add a piece to the puzzle of its anti-ALS molecular profile.

Pulmonary artery pressure response to percutaneous mitral valvuloplasty: Associated factors and clinical implications.

BACKGROUND: Pulmonary hypertension (PH) is a marker of poor outcome in mitral stenosis (MS), which improves after percutaneous mitral valvuloplasty (PMV). However, mechanical interventions for relief of valve obstruction often but not always reduce pulmonary pressures. This study aimed to assess the parameters associated with abnormal pulmonary artery pressure (PAP) response immediately after a successful PMV, and also its impact on long-term outcome. METHODS: A total of 181 patients undergoing PMV for rheumatic MS were prospectively enrolled. Invasive hemodynamic and echocardiographic measures were examined in all patients. Abnormal PAP response was defined as the mean PAP (mPAP) values unchanged at the end of the procedure. Long-term outcome was a composite endpoint of death, mitral valve replacement, repeat PMV, new onset of atrial fibrillation (AF), or stroke. RESULTS: The mean age was 44.1 ± 12.6 years, and 157 patients were women (86.7%). In the overall population, mPAP decreased from 33.4 ± 13.1 mmHg pre to 27.6 ± 9.8 mmHg post (p < 0.001). Following PMV, 52 patients (28.7%) did not have any reduction of mPAP immediately after the PMV. Multivariable analysis adjusting for baseline values of PAP and mitral valve area revealed that AF (Odds ratio [OR] 2.7, 95% [confidence interval] CI 1.3 to 6.7), maximum mitral valve leaflets displacement (OR 0.8, 95% CI 0.7 to 0.9), and post-procedural left ventricular compliance (OR 0.7, 95% CI 0.5 to 0.9) were predictors of a lack of improvement in mPAP. During a median follow-up of 4.4 years, the endpoint was reached in 56 patients (31%). The pulmonary pressure response to PMV was not an independent predictor of long-term events. CONCLUSIONS: In patients with MS undergoing PMV, pulmonary pressures may not reduce immediately after the procedure, despite adequate opening of the valve. Abnormal PAP response can be predicted from baseline clinical and valvular characteristics as well as post-procedural left ventricular compliance. The lack of any immediate reduction in mPAP is not associated with long-term adverse outcomes.

Effect of a 40-weeks multicomponent exercise program and branched chain amino acids supplementation on functional fitness and mental health in frail older persons.

BACKGROUND: The ageing process implies several physiological and psychological changes that hence affect the general health, mood states, and quality of life of older persons. Exercise and adequate nutrition are renowned non-pharmacological strategies that significantly delay and alleviate the adverse consequences of the ageing process. This study aimed to evaluate the effects of branched-chain amino acid (BCAA) supplementation and a multicomponent exercise program (ME) on the physical frailty and mood states of older persons. METHODS: 35 participants (women and men; 83 ± 3 years old) from residential care homes were submitted to a 40-week exercise-washout-retraining intervention (16 weeks of the elastic band based exercise and/or supplementation, 8 weeks of washout, and 16 weeks of multicomponent exercise and/or resupplementing), with or without BCAA supplementation. The experimental groups were: (i) ME plus BCAA supplementation (ME+BCAA); (ii) ME; (iii) BCAA supplementation (BCAA), and (iv) control group (CG). Fried's phenotype was used to assess frailty prevalence. Geriatric Depression Scale (GDS), Profile of Mood State (POMS), Mini-Mental State Examination (MMSE), were used to access mental health and cognition. The Short Physical Performance Battery (SPPB) was used to access functional capacity. Salivary testosterone levels (ST) were also determined to access the anabolic effects of the intervention. RESULTS: Exercise was effective in improving functional capacity and prevented the increase in frailty that occurred in the non-exercising CG, where the frailty scores increased over time (p < 0.01). BCAAs supplement alone had no impact on functional fitness, but in a short time (16 weeks) contributed to diminishing frailty and combined with exercise may have the potential to reduce the effect of a detraining period on functional capacity. Salivary testosterone levels correlated with handgrip strength and could be a useful indicator of susceptibility to frailty. No effects were found for mood states, cognition, and depression. CONCLUSION: This study showed that a long-term exercise program, independent of being multicomponent or strength elastic band-based, was effective in improving functional capacity and prevented an increase in frailty in frail and pre-frail older persons living in residential care homes.

The poorly conducted orchestra of steroid hormones, oxidative stress and inflammation in frailty needs a maestro: Regular physical exercise.

This review outlines the various factors associated with unhealthy aging which includes becoming frail and dependent. With many people not engaging in recommended exercise, facilitators and barriers to engage with exercise must be investigated to promote exercise uptake and adherence over the lifespan for different demographics, including the old, less affluent, women, and those with different cultural-ethnic backgrounds. Governmental and locally funded public health messages and environmental facilitation (gyms, parks etc.) can play an important role. Studies have shown that exercise can act as a conductor to balance oxidative stress, immune and endocrine functions together to promote healthy aging and reduce the risk for age-related morbidities, such as cardiovascular disease and atherosclerosis, and promote cognition and mood over the lifespan. Like a classic symphony orchestra, consisting of four groups of related musical instruments - the woodwinds, brass, percussion, and strings - the aging process should also perform in harmony, with compassion, avoiding the aggrandizement of any of its individual parts during the presentation. This review discusses the wide variety of molecular, cellular and endocrine mechanisms (focusing on the steroid balance) underlying this process and their interrelationships.

Penile Lymphoepithelioma-Like Carcinoma: A Rare Case With PD-L1 Expression.

Most malignant tumors of the penis are squamous cell carcinomas (SCC), being divided in 2 groups, one human papillomavirus (HPV)-related and another non-HPV-related, with lymphoepithelioma-like carcinoma (LELC) being one of the rarest HPV-related SCC. In this article, we report a case of a 50-year-old man who presented testicular swelling and pain for the past 3 months. A penile mass was identified, and the patient was submitted to a total penectomy. The penectomy specimen showed an ulcerated lesion at the glans reaching the cavernous bodies. Microscopic examination showed undifferentiated epithelial cells with syncytial growth pattern mix with a dense lymphoplasmacytic infiltrate, consistent with LELC. The tumor cells expressed p16 and all 3 different clones of PDL1 (22C3, SP263, and SP142). The patient is alive and well with a follow-up of 3 months. To our knowledge, this is the third LELC of the penis reported in literature and the first case reported with PDL1 expression.

Acute vestibular syndrome and hearing loss mimicking labyrinthitis as initial presentation of multiple sclerosis.

Acute vestibular syndrome is most often caused by vestibular neuritis or stroke, although demyelinating diseases may be responsible for 4% of all AVS episodes. The authors present the case of a previously healthy 17-year-old female patient complaining of spontaneous vertigo and right-sided hearing loss. Otoneurological examination suggested a peripheral vestibular cause and video head impulse test revealed a reduced vestibulo-ocular reflex gain. The presence of sensorineural hearing loss raised the suspicion of a central cause and prompted imaging evaluation. A brain MRI evidenced demyelinating lesions in the right middle cerebellar peduncle and the patient was ultimately diagnosed with Multiple Sclerosis.

Roller Compaction Scale-Up Made Simple: An Approximate Analytical Solution to Johanson's Rolling Theory.

An approximate analytical solution to Johanson's rolling theory is derived. It is shown that the solution yields a single dimensionless parameter invariant in process scale-up or equipment transfer, which relates the densification factor with process parameters (roll force and gap), geometric parameters (roll diameter and width) and material properties. It is shown that, to a first approximation, the model prediction does not depend on the nip angle evading the need to powder rheometry measurements such as wall friction and internal shear angle. The model is benchmarked against data obtained from pilot-scale roller compactors from different manufacturers as well as literature data from Nesarikar. The model yields good ribbon density predictions even when calibrating material properties from uniaxial die compression.

Management of laryngeal candidiasis: an evidence-based approach for the otolaryngologist.

PURPOSE: The authors aim to review available reports regarding laryngeal candidiasis and describe the existing evidence on the demographics, clinical manifestations, diagnosis, therapeutic options, and outcomes of this infection. METHODS: A review of articles on laryngeal candidiasis was conducted using PubMed® database from its inception through July 2019. RESULTS: Patients were mainly females presenting with complaints of dysphonia and associated gastroesophageal reflux history or inhaled corticosteroids use; although local predisposing factors were common, most patients were immunocompetent. The main anatomical affected subsite was the glottis with the presence of leukoplastic lesions. The diagnostic approach remains controversial, since some authors recommend prompt lesion biopsy and others rely on empirical antifungal treatment that showed effective results regarding symptoms and lesions resolution. CONCLUSION: Laryngeal Candida infection is thought to be a rare condition, with limited available literature. The correct diagnosis is difficult for the otolaryngologist and a high level of suspicion is required. The authors emphasize the need to include this condition into the differential diagnosis in patients with predisposing factors presenting with suspected lesions. In addition, the conservative diagnostic approach with antifungal treatment seems to provide effective outcomes, although comparative clinical studies between diagnostic options are lacking.

Behavior and biochemical responses of the polychaeta Hediste diversicolor to polystyrene nanoplastics.

Plastic debris has been reaching the world's oceans since it started being used. Multiple studies have been addressing the effects of microplastics in various organisms but, despite the increased scientific awareness, there is still a significant gap in knowledge when it comes to small-sized plastic particles of sizes below 100 nm. The aim of this study was to understand the effect of waterborne 100 nm polystyrene nanoplastics (PS NPs) on the marine polychaeta Hediste diversicolor, a keystone species in intertidal and coastal environments, in terms of behavior, neurotransmission, oxidative status, energy metabolism and oxidative damage. Results of PS NPs characterization showed an aggregation along the time and with increasing concentrations. Results also revealed a considerable impact of PS NPs on ecologically relevant endpoints like cholinesterase (ChE) and burrowing, but no increases in most of the parameters associated with oxidative stress. Protein carbonylation was found to be more sensitive to PS NPs effects than lipid peroxidation. Behavioral alterations induced by PS NPs may affect nutrient cycling and (endo-)benthic fauna. The data revealed in this study highlighted the potential consequences of NPs to benthic organisms and the need for further studies.

Metabolic syndrome and the composition of urinary calculi: is there any relation?

INTRODUCTION: Epidemiologic studies demonstrate that obesity and diabetes increase the prevalence of urinary lithiasis. Most of these studies did not stratify the chemical composition of calculi and the physiological mechanisms responsible for this increased risk are not well understood. This study aims to investigate the relation between the metabolic syndrome and the composition of the urinary calculi. MATERIAL AND METHODS: Observational and retrospective study of all urinary calculi analysis performed at the Centro Hospitalar do Tâmega e Sousa, Portugal - from January 2009 to September 2015. Calculi were analyzed by infrared spectroscopy. RESULTS: 302 analyses of urinary calculi were identified. Metabolic syndrome was diagnosed in 20.5% of patients. A total of 7 different mineral compounds were identified: 51.6% (N = 156) contained calcium oxalate, 41% (N = 124) calcium phosphate, 37.7% (N = 114) uric acid, 22.1% (N = 67) ammonium urate, 9.6% (N = 29) ammonium magnesium phosphate, 6.3% (N = 19) sodium urate and 1.3% (N = 4) contained cystine. Patients with metabolic syndrome presented a higher proportion of uric acid calculi (66.1% vs. 0%, p <0.001) and ammonium urate calculi (38.7% vs. 17%, p = 0.001). Patients without metabolic syndrome had a higher proportion of calcium oxalate calculi (58.8% vs. 24.2%, p <0.001) and calcium phosphate (46.7% vs. 19.4%, p <0.001). CONCLUSIONS: There is a statistically significant relation between metabolic syndrome and uric acid and ammonium urate calculi. Metabolic syndrome may be considered risk factor for this calculi and the diagnosis and treatment of this syndrome must be considered for urolithiasis prevention. Further studies are needed to better the understanding of physiological mechanisms underlying this relationship to improve our strategy of prevention of urinary lithiasis.

Primary mesenchymal chondrosarcoma of the kidney: A case report and review of literature.

Primary mesenchymal chondrosarcoma of the kidney is extremely rare, with only nine cases reported in the English literature. We report a new case of this disease. A 35-year-old man, presented with flank pain, episodic gross hematuria and a painless palpable mass in left abdominal quadrant. Computed tomography scan identified a left renal tumor with 20 cm, with no evidence of regional or metastatic spread disease. The patient underwent radical nephrectomy. The immunohistopathological diagnosis was mesenchymal chondrosarcoma of the kidney. At 18 months of follow-up, there was no evidence of recurrence or distant metastasis. Primary renal chondrosarcoma is so rare that its prognosis is unknown. Disease recurrence is unpredictable and when it is detected, the prognosis is poor. The radical nephrectomy with complete resection of the tumor with wide resection free margins is recommended, and the patients need long-term and close surveillance, with particular attention to local recurrence and uncommon sites of metastization.

Peripheral Facial Palsy in Emergency Department.

INTRODUCTION: Peripheral facial palsy (PFP) is commonly diagnosed in every emergency department. Despite being a benign condition in most cases, PFP causes loss in quality of life mostly due to facial dysmorphia. The etiology of PFP remains unknown in most cases, while medical opinion on epidemiology, risk factors and optimal treatment is not consensual. The aim of this study was to review the demographic characteristics of our patients and the medical care administered in our emergency department. MATERIALS AND METHODS: Emergency episodes occurring in a 4-year period and codified as facial nerve pathology were analyzed. IBM SPSS software was used for statistical analysis. RESULTS: In total, 582 emergency episodes were obtained. Due to inexpressive representation of other causes of PFP in our study, we focused our analyses on the 495 patients who were considered to have idiopathic PFP. There was equal distribution among genders, and all age ranges were affected. There were no clear epidemic phenomena. Hypertension was not a statistically significant risk factor for Bell's palsy. Most patients sought medical care in the early stages of the disease and complained of isolated facial weakness. Most patients had mild-to-moderate symptoms. Previous upper way infections (PUAI) were more frequent among children. There was a statistically significant difference regarding computed tomography (CT) scan requests among specialties. CONCLUSION: Epidemiologic findings were consistent with most literature on Bell's palsy. Drug therapy is widely used and follows current guidelines. The role of PUAI in the pediatric population must be investigated. Despite evidence of good medical practice, there was an excess of CT scans requested by physicians other than otorhinolaryngologists.

The Versatile Posterior Auricular Fascia in Secondary Rhinoplasty Procedures.

BACKGROUND: Secondary rhinoplasty often involves the addition of autogenous graft material to add volume, structure, support and to camouflage cartilage and bone grafts. A variety of fascias have been used to camouflage, wrap and give "fill" in secondary rhinoplasty. The posterior auricular fascia is a source of material ideal for such purposes, and its quantity, anatomical structure and ease of harvest with minimal donor site morbidity make it a versatile and attractive autogenous graft. METHODS: The clinical records of patients receiving autogenous posterior auricular fascial grafts were reviewed. There were two main uses of this graft material, one was to cover the tip reconstruction in secondary rhinoplasties under thin tip skin. This is a camouflage graft. The second use is for fill and augmentation, especially for the nasal dorsum and as an interpostitional graft between the dorsum and the tip. CONCLUSION: The posterior auricular fascial graft has many potential uses in secondary rhinoplasties and is readily harvested as a generous graft concurrent to conchal cartilage harvest and with a concealed scar behind the ear. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Small Intestinal Submucosa Grafting for Peyronie Disease: Outcomes and Patient Satisfaction.

OBJECTIVE: To evaluate surgical outcomes and complications and assess overall patient satisfaction after small intestinal submucosa (SIS) grafting for Peyronie disease. METHODS: Twenty-eight patients were treated with tunical incision and grafting with SIS. Mean age of the patients was 58 (range: 43-71) years. A preoperative protocol was applied to all patients. Patients were also evaluated at follow-up clinic visits. The International Index of Erectile Function, a modified Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire, postoperative self-reports, and clinical characteristics were used to measure outcomes. RESULTS: Hypertension, hypercholesterolemia, and type 2 diabetes were reported in 53,6%, 46,4%, and 28,6% of patients, respectively. Previous penile trauma was reported by 10,7%. The mean operative time was 151 ± 23 minutes. Average follow-up was 18 months (range: 3-36). The only surgical complication was 1 case of infected hematoma treated with surgical drainage. Self-reported complete resolution of curvature was 82,1%. Subjective perception of penile shortening was reported by 71,4% of patients. However, only 4 patients objectively showed postoperative penile shortening. Erectile function was completely preserved in 64,2%. Four patients complained of erectile dysfunction despite medication, even though no objective vascular etiology was shown on postoperative penile Doppler ultrasound. Overall, 82,2% of patients reported high levels of satisfaction. CONCLUSION: Surgical treatment of Peyronie disease using SIS grafting is a safe option, with low rate of major complications. It has good surgical outcomes and high patient satisfaction rates.

Influence of the Pectoralis Major Muscle Sling in Chest Wall-Based Flap Suspension After Vertical Mammaplasty: Ten-Year Follow-Up.

BACKGROUND: The pectoralis muscle sling has proven to be a suitable alternative technique for long-term results in breast parenchyma suspension. Although the pectoralis muscle sling has been subjectively observed to reduce the bottoming-out effect with a bipedicled muscle flap (muscular loop), there has not been a study to objectively or numerically prove it. OBJECTIVES: This study aimed to radiologically evaluate the influence of a pectoralis muscle sling in supporting the chest wall-based flap after a vertical breast-reduction technique. METHODS: Twenty-one female patients underwent a vertical breast reduction with the chest wall-based flap and were randomly divided into two subgroups. Ten patients were in subgroup (S), which consisted of patients with a muscle sling. Eleven patients without the muscle sling technique were assigned as a control group (C). Periodic radiological examinations were performed at 1, 3, 6, and 12 months and then at 10 years postoperatively to analyze the breast flap and any migration with respect to three titanium clips placed intraoperatively on the chest wall parenchyma flap. RESULTS: Patients in subgroup S had a significantly higher difference in migration of the chest wall-based flaps between the first day and 10 years postoperatively when compared with patients in subgroup C (P < .001), as shown by the distances measured between titanium clip locations. CONCLUSIONS: After 10 years of follow-up, there were changes in chest wall-based flap bottoming-out in patients in whom a pectoralis major muscle sling was utilized compared with those patients without it. Thus, a pectoralis major muscle sling seems to provide greater and longer-lasting support to the flap position on the patient's chest. LEVEL OF EVIDENCE: 2 Therapeutic.