Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma.

BACKGROUND: Phase 1-2 trials involving patients with resectable, macroscopic stage III melanoma have shown that neoadjuvant immunotherapy is more efficacious than adjuvant immunotherapy. METHODS: In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma, in a 1:1 ratio, to receive two cycles of neoadjuvant ipilimumab plus nivolumab and then undergo surgery or to undergo surgery and then receive 12 cycles of adjuvant nivolumab. Only the patients in the neoadjuvant group who had a partial response or nonresponse received subsequent adjuvant treatment. The primary end point was event-free survival. RESULTS: A total of 423 patients underwent randomization. At a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% (99.9% confidence interval [CI], 73.8 to 94.8) in the neoadjuvant group and 57.2% (99.9% CI, 45.1 to 72.7) in the adjuvant group. The difference in restricted mean survival time was 8.00 months (99.9% CI, 4.94 to 11.05; P<0.001; hazard ratio for progression, recurrence, or death, 0.32; 99.9% CI, 0.15 to 0.66). In the neoadjuvant group, 59.0% of the patients had a major pathological response, 8.0% had a partial response, 26.4% had a nonresponse (>50% residual viable tumor), and 2.4% had progression; in 4.2%, surgery had not yet been performed or was omitted. The estimated 12-month recurrence-free survival was 95.1% among patients in the neoadjuvant group who had a major pathological response, 76.1% among those who had a partial response, and 57.0% among those who had a nonresponse. Adverse events of grade 3 or higher that were related to systemic treatment occurred in 29.7% of the patients in the neoadjuvant group and in 14.7% in the adjuvant group. CONCLUSIONS: Among patients with resectable, macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab followed by surgery and response-driven adjuvant therapy resulted in longer event-free survival than surgery followed by adjuvant nivolumab. (Funded by Bristol Myers Squibb and others; NADINA ClinicalTrials.gov number, NCT04949113.).

L-Ergothioneine slows the progression of age-related hearing loss in CBA/CaJ mice.

The naturally occurring amino acid, l-ergothioneine (EGT), has immense potential as a therapeutic, having shown promise in the treatment of other disease models, including neurological disorders. EGT is naturally uptaken into cells via its specific receptor, OCTN1, to be utilized by cells as an antioxidant and anti-inflammatory. In our current study, EGT was administered over a period of 6 months to 25-26-month-old CBA/CaJ mice as a possible treatment for age-related hearing loss (ARHL), since presbycusis has been linked to higher levels of cochlear oxidative stress, apoptosis, and chronic inflammation. Results from the current study indicate that EGT can prevent aging declines of some key features of ARHL. However, we found a distinct sex difference for the response to the treatments, for hearing - Auditory Brainstem Responses (ABRs) and Distortion Product Otoacoustic Emissions (DPOAEs). Males exhibited lower threshold declines in both low dose (LD) and high dose (HD) test groups throughout the testing period and did not display some of the characteristic aging declines in hearing seen in Control animals. In contrast, female mice did not show any therapeutic effects with either treatment dose. Further confirming this sex difference, EGT levels in whole blood sampling throughout the testing period showed greater uptake of EGT in males compared to females. Additionally, RT-PCR results from three tissue types of the inner ear confirmed EGT activity in the cochlea in both males and females. Males and females exhibited significant differences in biomarkers related to apoptosis (Cas-3), inflammation (TNF-a), oxidative stress (SOD2), and mitochondrial health (PGC1a).These changes were more prominent in males as compared to females, especially in stria vascularis tissue. Taken together, these findings suggest that EGT has the potential to be a naturally derived therapeutic for slowing down the progression of ARHL, and possibly other neurodegenerative diseases. EGT, while effective in the treatment of some features of presbycusis in aging males, could also be modified into a general prophylaxis for other age-related disorders where treatment protocols would include eating a larger proportion of EGT-rich foods or supplements. Lastly, the sex difference discovered here, needs further investigation to see if therapeutic conditions can be developed where aging females show better responsiveness to EGT.

Managing a Pigmented Corneal Ulcer in a 58-Year-Old Patient.

We report on a case study involving a 58-year-old male with a pigmented corneal ulcer. The patient presented with a two-month history of an unresolved corneal ulcer in the oculus sinister (OS), accompanied by increasing ocular discomfort. His best corrected visual acuity (BCVA) was 20/20 oculus dexter and hand motion OS. Examination of OS revealed mild conjunctival injection, diffuse corneal edema, and the presence of a central pigmented lesion. Microbiological analysis via culture identified the causative agent as Ochroconis fungi, belonging to the dematiaceous species. Subsequently, the patient's condition was managed through a comprehensive regimen that included multiple topical antifungal agents, a topical antibiotic, and povidone-iodine drops. After two months of treatment, the patient exhibited improvement in his condition. His BCVA improved to counting fingers at a distance of two feet OS.

The ripple effect of animal disease outbreaks on food systems: The case of African Swine Fever on the Chinese pork market.

Research on animal health economics has emphasised the importance of accounting for the indirect economic effects of animal disease outbreaks. Although recent studies have advanced in this direction by assessing consumer and producer welfare losses due to asymmetric price adjustments, potential over-shifting effects along the supply chain and spill-overs to substitute markets have been under-examined. This study contributes to this field of research by assessing the direct and indirect effects of the African swine fever (ASF) outbreak on the pork market in China. We employ impulse response functions estimated by local projection to calculate the price adjustments for consumers and producers, as well as the cross-effect in other meat markets. The results show that the ASF outbreak led to increases in both farmgate and retail prices but the rise in retail prices exceeded the corresponding change in farmgate prices. Furthermore, beef and chicken prices also rose, demonstrating the spill-over impacts of the outbreak to other markets. Overall, the evidence illustrates that a disruption in one part of a food system can have significant ripple effects across other parts of the system.

Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

BACKGROUND: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. METHODS: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. RESULTS: A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. CONCLUSIONS: In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than among those who received ipilimumab. (Funded by the Dutch Cancer Society and others; ClinicalTrials.gov number, NCT02278887.).

Post-translational modifications and age-related hearing loss.

Post-translational modifications (PTMs) affect nearly all systems of the human body due to their role in protein synthesis and functionality. These reversible and irreversible modifications control the structure, localization, activity, and properties of proteins. For this reason, PTMs are essential in regulating cellular processes and maintaining homeostasis. Diseases such as Alzheimer's, cardiovascular disease, diabetes, cancer, and many others have been linked to dysfunctions of PTMs. Recent research has also shown that irregularities in PTMs can be linked to hearing loss, including age-related hearing loss (ARHL) - the number one communication disorder and one of the top neurodegenerative diseases in our aging population. So far, there has been no FDA approved treatment for ARHL; however, translational studies investigating PTMs involvement in ARHL show promising results. In this review, we summarize key findings for PTMs within the auditory system, the involvement of PTMs with aging and ARHL, and lastly discuss potential treatment options focusing on utilizing PTMs as biomarkers and therapeutic pathway components.

Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial.

Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates (pRRs) in clinical stage III nodal melanoma, and pathologic response is strongly associated with prolonged relapse-free survival (RFS). The PRADO extension cohort of the OpACIN-neo trial ( NCT02977052 ) addressed the feasibility and effect on clinical outcome of using pathologic response after neoadjuvant ipilimumab and nivolumab as a criterion for further treatment personalization. In total, 99 patients with clinical stage IIIb-d nodal melanoma were included and treated with 6 weeks of neoadjuvant ipilimumab 1 mg kg-1 and nivolumab 3 mg kg-1. In patients achieving major pathologic response (MPR, ≤10% viable tumor) in their index lymph node (ILN, the largest lymph node metastasis at baseline), therapeutic lymph node dissection (TLND) and adjuvant therapy were omitted. Patients with pathologic partial response (pPR; >10 to ≤50% viable tumor) underwent TLND only, whereas patients with pathologic non-response (pNR; >50% viable tumor) underwent TLND and adjuvant systemic therapy ± synchronous radiotherapy. Primary objectives were confirmation of pRR (ILN, at week 6) of the winner neoadjuvant combination scheme identified in OpACIN-neo; to investigate whether TLND can be safely omitted in patients achieving MPR; and to investigate whether RFS at 24 months can be improved for patients achieving pNR. ILN resection and ILN-response-tailored treatment were feasible. The pRR was 72%, including 61% MPR. Grade 3-4 toxicity within the first 12 weeks was observed in 22 (22%) patients. TLND was omitted in 59 of 60 patients with MPR, resulting in significantly lower surgical morbidity and better quality of life. The 24-month relapse-free survival and distant metastasis-free survival rates were 93% and 98% in patients with MPR, 64% and 64% in patients with pPR, and 71% and 76% in patients with pNR, respectively. These findings provide a strong rationale for randomized clinical trials testing response-directed treatment personalization after neoadjuvant ipilimumab and nivolumab.

Predator-prey landscapes of large sharks and game fishes in the Florida Keys.

Interspecific interactions can play an essential role in shaping wildlife populations and communities. To date, assessments of interspecific interactions, and more specifically predator-prey dynamics, in aquatic systems over broad spatial and temporal scales (i.e., hundreds of kilometers and multiple years) are rare due to constraints on our abilities to measure effectively at those scales. We applied new methods to identify space-use overlap and potential predation risk to Atlantic tarpon (Megalops atlanticus) and permit (Trachinotus falcatus) from two known predators, great hammerhead (Sphyrna mokarran) and bull (Carcharhinus leucas) sharks, over a 3-year period using acoustic telemetry in the coastal region of the Florida Keys (USA). By examining spatiotemporal overlap, as well as the timing and order of arrival at specific locations compared to random chance, we show that potential predation risk from great hammerhead and bull sharks to Atlantic tarpon and permit are heterogeneous across the Florida Keys. Additionally, we find that predator encounter rates with these game fishes are elevated at specific locations and times, including a prespawning aggregation site in the case of Atlantic tarpon. Further, using machine learning algorithms, we identify environmental variability in overlap between predators and their potential prey, including location, habitat, time of year, lunar cycle, depth, and water temperature. These predator-prey landscapes provide insights into fundamental ecosystem function and biological conservation, especially in the context of emerging fishery-related depredation issues in coastal marine ecosystems.

Cochlear Inflammaging in Relation to Ion Channels and Mitochondrial Functions.

The slow accumulation of inflammatory biomarker levels in the body-also known as inflammaging-has been linked to a myriad of age-related diseases. Some of these include neurodegenerative conditions such as Parkinson's disease, obesity, type II diabetes, cardiovascular disease, and many others. Though a direct correlation has not been established, research connecting age-related hearing loss (ARHL)-the number one communication disorder and one of the most prevalent neurodegenerative diseases of our aged population-and inflammaging has gained interest. Research, thus far, has found that inflammatory markers, such as IL-6 and white blood cells, are associated with ARHL in humans and animals. Moreover, studies investigating ion channels and mitochondrial involvement have shown promising relationships between their functions and inflammaging in the cochlea. In this review, we summarize key findings in inflammaging within the auditory system, the involvement of ion channels and mitochondrial functions, and lastly discuss potential treatment options focusing on controlling inflammation as we age.

Roles of Key Ion Channels and Transport Proteins in Age-Related Hearing Loss.

The auditory system is a fascinating sensory organ that overall, converts sound signals to electrical signals of the nervous system. Initially, sound energy is converted to mechanical energy via amplification processes in the middle ear, followed by transduction of mechanical movements of the oval window into electrochemical signals in the cochlear hair cells, and finally, neural signals travel to the central auditory system, via the auditory division of the 8th cranial nerve. The majority of people above 60 years have some form of age-related hearing loss, also known as presbycusis. However, the biological mechanisms of presbycusis are complex and not yet fully delineated. In the present article, we highlight ion channels and transport proteins, which are integral for the proper functioning of the auditory system, facilitating the diffusion of various ions across auditory structures for signal transduction and processing. Like most other physiological systems, hearing abilities decline with age, hence, it is imperative to fully understand inner ear aging changes, so ion channel functions should be further investigated in the aging cochlea. In this review article, we discuss key various ion channels in the auditory system and how their functions change with age. Understanding the roles of ion channels in auditory processing could enhance the development of potential biotherapies for age-related hearing loss.

Influence of the Craniocervical Posture on Tongue Strength and Endurance.

Tongue strength has an important role in the swallowing process, and previous research has suggested that tongue position, concerning the craniomandibular region, could affect the oral function. This study aimed to evaluate the strength and endurance of three areas of the tongue in three experimentally induced craniocervical postures. A cross-sectional study with a nonprobabilistic sample of 37 participants (mean age: 3.85 ± 3.64 years; 20 men, 17 women) was performed. Tongue strength and endurance were assessed using a pressure device entitled Iowa Oral Performance Instrument (IOPI), in three different craniocervical positions: neutral head position (NHP), anterior head translation-or forward head position (FHP), and posterior head translation-or retracted head position (RHP). Measurements taken using the IOPI system showed significant differences in tongue strength for the anterior (p = 0.015) and middle areas of the tongue (p = 0.01). Significant differences were observed in analysis of variance (ANOVA) in the FHP (p = 0.02) and NHP (p = 0.009). The results of tongue endurance measurements showed statistically significant differences for FHP (p = 0.001), NHP (p = 0.00), and RHP (p = 0.007). The craniocervical position influences tongue strength, especially in the anterior and middle tongue areas, concerning the posterior, and, in the anterior and neutral head posture, regarding the retracted position. No differences were found in tongue resistance between the various craniocervical positions, but differences were found in resistance between the different tongue areas.

Immediate effects of COVID-19 on the global dairy sector.

CONTEXT: The emergence and rapid spread of the coronavirus disease (COVID-19) has posed an unprecedented threat to both societies and economies. The dairy sector is an example of the challenges that food supply chains have faced due to the pandemic. OBJECTIVE: This study aims to provide primary evidence of the immediate effects of COVID-19 on the global dairy sector, particularly focusing on the outcome of the implemented response mechanisms, and the potential medium and long-term implications of the pandemic on the sector. METHODS: We employed a longitudinal qualitative analysis framework that combines the use of questionnaires, media-search, focus-group discussions, semi-structured interviews, and secondary evidence reviews. Information was gathered at two points in time: three months after the beginning of the outbreak and one year later. We applied this framework in five different geographical regions: Africa, Asia, Europe, Latin America, and North America. RESULTS AND CONCLUSIONS: Our study indicates that the pandemic has been perceived as a series of episodes affecting the sector from both demand and supply sides. These waves have impacted the sector differently depending on regions and countries' trade profiles, relative resource scarcity, per capita income, and market structure. Although in one year the sector has mostly recovered from the shock, the analysis concludes that the pandemic has accelerated on-going structural changes taking place in the dairy sector. SIGNIFICANCE: The study expands existing knowledge about the effects of the pandemic on the dairy sector and adds to the newly evolving literature about the medium and long-term effects of the COVID-19 on food systems across the globe. Despite the preliminary nature of the results, they provide important insights to inform sectorial policy discussions.

Microbiological and process variability using biological indicators of inactivation (BIIs) based on Bacillus cereus spores of food and fish-based animal by-products to evaluate microwave heating in a pilot plant.

Microwave processing can be a valid alternative to conventional heating for different types of products. It enables a more efficient heat transfer in the food matrix, resulting in higher quality products. However, for many food products a uniform temperature distribution is not possible because of heterogeneities in their physical properties and non-uniformtiy in the electric field pattern. Hence, the effectiveness of microwave inactivation treatments is influenced by both intrinsic (differences between cells) and extrinsic variability (non-uniform temperature). Interpreting the results of the process and considering its impact on microbial inactivation is essential to ensure effective and efficient processing. In this work, we quantified the variability in microbial inactivation attained in a microwave pasteurization treatment with a tunnel configuration at pilot-plant scale. The configuration of the equipment makes it impossible to measure the product temperature during treatment. For that reason, variability in microbial counts was measured using Biological Inactivation Indicators (BIIs) based on spherical particles of alginate inoculated with spores of Bacillus spp. The stability of the BIIs and the uncertainty associated to them was assessed using preliminary experiments in a thermoresistometer. Then, they were introduced in the food product to analyse the microbial inactivation in different points of the products during the microwave treatment. Experiments were made in a vegetable soup and a fish-based animal by-product (F-BP). The results show that the variation in the microbial counts was higher than expected based on the biological variability estimated in the thermoresistometer and the uncertainty of the BIIs. This is due to heterogeneities in the temperature field (measured using a thermographic camera), which were higher in the F-BP than in the vegetable soup. Therefore, for the process studied, extrinsic variability was more relevant than intrinsic variability. The methodology presented in this work can be a valid method to evaluate pasteurization treatments of foods processed by heating, providing valuable information of the microbial inactivation achieved. It can contribute to design microwave processes for different types of products and for product optimization.

Application of machine learning algorithms to identify cryptic reproductive habitats using diverse information sources.

Information on ecological systems often comes from diverse sources with varied levels of complexity, bias, and uncertainty. Accordingly, analytical techniques continue to evolve that address these challenges to reveal the characteristics of ecological systems and inform conservation actions. We applied multiple statistical learning algorithms (i.e., machine learning) with a range of information sources including fish tracking data, environmental data, and visual surveys to identify potential spawning aggregation sites for a marine fish species, permit (Trachinotus falcatus), in the Florida Keys. Recognizing the potential complementarity and some level of uncertainty in each information source, we applied supervised (classic and conditional random forests; RF) and unsupervised (fuzzy k-means; FKM) algorithms. The two RF models had similar predictive performance, but generated different predictor variable importance structures and spawning site predictions. Unsupervised clustering using FKM identified unique site groupings that were similar to the likely spawning sites identified with RF. The conservation of aggregate spawning fish species depends heavily on the protection of key spawning sites; many of these potential sites were identified here for permit in the Florida Keys, which consisted of relatively deep-water natural and artificial reefs with high mean permit residency periods. The application of multiple machine learning algorithms enabled the integration of diverse information sources to develop models of an ecological system. Faced with increasingly complex and diverse data sources, ecologists, and conservation practitioners should find increasing value in machine learning algorithms, which we discuss here and provide resources to increase accessibility.

El proceso de transformación laboral en Uruguay / The process of work transformation in Uruguay / O processo de transformação do trabalho no Uruguai

El siguiente artículo pretende caracterizar el desarrollo del mundo del trabajo en Uruguay, tratando de capturar modalidades sobresalientes que definen una época. Para ello establece una periodización torno a las diferentes innovaciones que van siendo incorporadas a la producción y el aprovechamiento del trabajo. Este proceso tiene directa vinculación con el desarrollo del capita-lismo monopolista hasta nuestros días. Se intenta reproducir momentos que permiten comprender un lento proceso de precarización y empobrecimiento de los trabajadores en el largo plazo. En el final se recupera el trayecto recorrido, intentando encontrar en aquella síntesis de conclusiones un escenario para situar la discusión contemporánea, con tendencia a la precarización del trabajo, la uberización y el avance del capitalismo de plataformas

The present article has as an objective to characterize the world deve-lopment of work in Uruguai by analyzing important methods that define a period. In this regard, a periodization was established regarding the different innovations that have been incorporated to production and utilization of work. This process has a direct link with the development of monopoly capitalism until this days. The purpose was to reproduce the steps that allowed the understanding of the slow process of precarization and impoverishment of workers. Finally, this work tried to establish a possible scenario in the contemporary context tending to a precarization of work, uberization and platform capitalism advance

O presente artigo tem como objetivo caracterizar o desenvolvimento do mundo do trabalho no Uruguai, analisando modalidades marcantes que definem uma época. Para isso, se estabeleceu uma periodização em torno das diferentes inovações que foram sendo incorporadas à produção e ao aproveitamento do trabalho. Este processo possui vinculação direta com o desenvolvimento do capitalismo monopolista até o presente momento. Pretendeu-se reproduzir os passos que permitem compreender o lento processo de precarização e empobrecimento dos trabalhadores a longo prazo. Por fim, a partir dessa trajetória se procurou estabelecer um cenário para situar a discussão em um contexto contemporâneo, com tendência à precarização do trabalho, à uberização e ao avanço do capitalismo de plataforma

Decreased biochemical progression in patients with castration-resistant prostate cancer using a novel mefenamic acid anti-inflammatory therapy: A randomized controlled trial.

Prostate cancer (PCa) is the second most common non-dermatological cancer in men and is a growing public health problem. Castration-resistant disease (CRD) is the most advanced stage of the disease and is difficult to control. Patients with CRD may no longer accept conventional therapies as they are not in appropriate clinical conditions or they refuse to receive it. Given that inflammation is an essential component of CRD origin and progression, anti-inflammatory agents could be a therapeutic option with fenamates as one of the proposed choices. A prospective, randomized, double-blinded, 2-arm, parallel group, phase II-III clinical trial was performed involving 20 patients with CRD-PCa (with a prostate specific antigen level <100 ng/ml) that were undergoing androgen deprivation therapy (ADT) and did not accept any established treatment for that disease stage. In addition to ADT, 10 patients received placebo and 10 received mefenamic acid (500 mg orally every 12 h) for 6 months. The primary endpoint was the change in serum prostate-specific antigen (PSA) at 6 months. The PSA levels decreased significantly with mefenamic acid (an average 42% decrease), whereas there was an average 55% increase in the placebo group (P=0.024). In the patients treated with the placebo, 70% had biochemical disease progression (an increase of ≥25% in PSA levels), which did not occur in any of the patients treated with mefenamic acid (relative risk=0.12; 95% confidence interval, 0.01-0.85; P=0.033). There was a significant increase in quality of life (EQ-5D-5L score) and body mass index (BMI) with the experimental treatment. In conclusion, mefenamic acid administration decreased biochemical progression in patients with castration resistant PCa, improved their quality of life and increased their BMI. Future studies are required in order to strengthen the findings of the present clinical trial. Trial registration, Cuban Public Registry of Clinical Trials Database RPCEC00000248, August 2017.

Effect of Manual Therapy and Therapeutic Exercise Applied to the Cervical Region on Pain and Pressure Pain Sensitivity in Patients with Temporomandibular Disorders: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the effectiveness of cervical manual therapy (MT) on patients with temporomandibular disorders (TMDs) and to compare cervico-craniomandibular MT vs cervical MT. DESIGN: Systematic review and meta-analysis (MA). METHODS: A search in PubMed, EMBASE, PEDro, and Google Scholar was conducted with an end date of February 2019. Two independent reviewers performed the data analysis, assessing the relevance of the randomized clinical trials regarding the studies' objectives. The qualitative analysis was based on classifying the results into levels of evidence according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Regarding cervical MT, MA included three studies and showed statistically significant differences in pain intensity reduction and an increase in masseter pressure pain thresholds (PPTs), with a large clinical effect. In addition, the results showed an increase in temporalis PPT, with a moderate clinical effect. MA included two studies on cervical MT vs cervico-craniomandibular MT interventions and showed statistically significant differences in pain intensity reduction and pain-free maximal mouth opening, with a large clinical effect. CONCLUSIONS: Cervical MT treatment is more effective in decreasing pain intensity than placebo MT or minimal intervention, with moderate evidence. Cervico-craniomandibular interventions achieved greater short-term reductions in pain intensity and increased pain-free MMO over cervical intervention alone in TMD and headache, with low evidence.

Is aerobic exercise helpful in patients with migraine? A systematic review and meta-analysis.

PURPOSE: To assess the effects of aerobic exercise (AE) on patients with migraine in terms of pain intensity, frequency and duration of migraine, and quality of life. METHODS: A systematic review and meta-analysis of randomized controlled trials were conducted. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for relevant outcomes and were pooled in a meta-analysis using the random-effects model. RESULTS: A total of 10 articles from 1950 to 2019 were included, involving 508 patients. The meta-analysis showed statistically significant differences in the decrease in pain intensity (five studies, n = 166; SMD = 1.25; 95% CI 0.47-2.04), frequency (six studies, n = 214; SMD = 0.76; 95% CI 0.32-1.2) and duration of migraine (four studies, n = 106; SMD = 0.41; 95% CI 0.03-0.8), in the short-term. In addition, the meta-analysis showed statistically significant differences in the increase in quality of life (four studies, n = 150; SMD = 2.7; 95% CI 1.17-4.24), even though the Egger's test suggested significant evidence of publication bias for the analysis of quality of life (intercept = 5.81; t = 6.97; P = .02). CONCLUSIONS: There is low- and moderate-quality evidence that in patients with migraine AE can decrease the pain intensity, frequency and duration of migraine and can also increase quality of life.

Seasonal occupancy and connectivity amongst nearshore flats and reef habitats by permit Trachinotus falcatus: considerations for fisheries management.

We used acoustic telemetry to quantify permit Trachinotus falcatus habitat use and connectivity in proximity to the Florida Keys, USA, and assessed these patterns relative to current habitat and fisheries management practices. From March 2017 to June 2018, 45 permit tagged within 16 km of the lower Florida Keys were detected at stationary acoustic receivers throughout the south Florida region, the majority of which remained within the Special Permit Zone, where more extensive fisheries harvest regulations are implemented. There was a high level of connectivity between nearshore flats (i.e., <3 m water depth) and the Florida reef tract (FRT; 15-40 m water depth), with 75% of individuals detected in both habitats. These locations probably function primarily as foraging and spawning habitats, respectively. Permit occupancy on the FRT peaked during the months of March-September, with the highest number of individuals occurring there in April and May. Specific sites on the FRT were identified as potentially important spawning locations, as they attracted a high proportion of individuals that exhibited frequent visits with high residency durations. There were also significant positive relationships between seasonal habitat-use metrics on the FRT and an empirical permit gonadosomatic index. Large aggregations of permit at spawning sites on the FRT are potentially vulnerable to the effects of fishing (including predation during catch and release) at a critical point in their life cycle. These data on permit space use and movement, coupled with knowledge of stressors on their ecology, provide insights for implementing science-based strategic management plans.

Uso de la técnica quirúrgica de Bernard-Burow modificada en un paciente con carcinoma espinocelular del labio superior / Use of Bernard-Burow surgical technique modified in a patient with squamous-cell carcinoma of the upper lip

Se presenta el caso clínico de un paciente de 61 años de edad, con antecedentes de fumador activo, quien fuera remitido de su área de salud al Servicio de Cirugía Maxilofacial del Hospital Provincial Docente Dr Joaquín Castillo Duany de Santiago de Cuba, por presentar una lesión en el borde bermejo del labio superior, cuyos exámenes clínico e histopatológico revelaron que se trataba de un carcinoma espinocelular. Durante el tratamiento quirúrgico se aplicó una modificación de la técnica de Bernard-Burow, que permitió evitar la pérdida de la subunidad correspondiente al filtrum y la asimetría de las comisuras labiales, resultantes del método tradicional(U)

The case report of a 61 years patient is presented, with a history of active smoking who was referred from his health area to the Maxillofacial Surgery Service of Dr Joaquín Castillo Duany Teaching Provincial Hospital in Santiago de Cuba, due to an injury in the red border of the upper lip whose clinical and histopathological exams revealed that it was a squamous-cell carcinoma. During the surgical treatment a modification of the Bernard-Burow technique was applied that allowed to avoid the loss of the subunit corresponding to the filtrum and the asymmetry of the labial corners, resulting from the traditional method(AU)