Experiences of people with Long Covid with a digital physiotherapy intervention: A qualitative study.

PURPOSE: Long Covid syndrome is a multiorgan condition with multiple sequelae affecting quality of life, capacity to work and daily activities. The advantages that new technologies can offer are presented as an opportunity in the current healthcare framework. OBJECTIVE: This research aimed to explore people with Long Covid's experiences with a digital physiotherapy practice intervention, during four weeks. METHODS: Qualitative semistructured interviews were conducted by video call. Thirty-two Long Covid participants were invited to join an in-depth interview once the intervention was completed. Participants were queried on their intervention experiences and perceptions, as well as any lifestyle changes made, as a result of receiving digital physiotherapy practice. The interviews were transcribed and analysed using inductive qualitative content analysis. RESULTS: In-depth qualitative analysis has revealed four themes that reflect participants' perceptions of digital physiotherapy intervention. The helpfulness of the exercises, interaction with the physiotherapist, the domestic use of technology and the future of digital health practice were the topics highlighted by Long Covid participants. Some improvements have been suggested including video sounds and the need to introduce face-to-face sessions. Participants stated that interventions were helpful and superior to printed exercise sheets, mobile phone apps and usual care received. This intervention did not present major barriers, highlighting the importance of personalized care and continuity in the provision of health services. CONCLUSION: The digital physiotherapy practice is perceived by people with Long Covid as an appropriate method for the care of their health needs. Participants stated the need for this type of intervention in the public health system, where it would eliminate waiting lists, facilitate accessibility and improve existing care. PATIENT AND PUBLIC CONTRIBUTION: Participants contributed to the interpretation of the data acquired in the interview. CLINICAL TRIAL REGISTRATION: Trial registration NCT04742946.

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer.

BACKGROUND: CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer. RESULTS: Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9-18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone. CONCLUSION: Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0-9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.

Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids.

Mutations in pitrilysin metallopeptidase 1 (PITRM1), a mitochondrial protease involved in mitochondrial precursor processing and degradation, result in a slow-progressing syndrome characterized by cerebellar ataxia, psychotic episodes, and obsessive behavior, as well as cognitive decline. To investigate the pathogenetic mechanisms of mitochondrial presequence processing, we employed cortical neurons and cerebral organoids generated from PITRM1-knockout human induced pluripotent stem cells (iPSCs). PITRM1 deficiency strongly induced mitochondrial unfolded protein response (UPRmt) and enhanced mitochondrial clearance in iPSC-derived neurons. Furthermore, we observed increased levels of amyloid precursor protein and amyloid ß in PITRM1-knockout neurons. However, neither cell death nor protein aggregates were observed in 2D iPSC-derived cortical neuronal cultures. On the other hand, over time, cerebral organoids generated from PITRM1-knockout iPSCs spontaneously developed pathological features of Alzheimer's disease (AD), including the accumulation of protein aggregates, tau pathology, and neuronal cell death. Single-cell RNA sequencing revealed a perturbation of mitochondrial function in all cell types in PITRM1-knockout cerebral organoids, whereas immune transcriptional signatures were substantially dysregulated in astrocytes. Importantly, we provide evidence of a protective role of UPRmt and mitochondrial clearance against impaired mitochondrial presequence processing and proteotoxic stress. Here, we propose a novel concept of PITRM1-linked neurological syndrome whereby defects of mitochondrial presequence processing induce an early activation of UPRmt that, in turn, modulates cytosolic quality control pathways. Thus, our work supports a mechanistic link between mitochondrial function and common neurodegenerative proteinopathies.

The Benefits of a Therapeutic Exercise and Educational Intervention Program on Central Sensitization Symptoms and Pain-Related Fear Avoidance in Breast Cancer Survivors.

BACKGROUND: Central sensitization symptoms and pain-related fear avoidance are two common problems in breast cancer survivors. Non-pharmacologic interventions such as therapeutic exercise and patient education can be effective in this population. AIMS: This study aimed to: (1) analyze the benefits of a therapeutic exercise and educational program on central sensitization symptoms and pain-related fear avoidance in breast cancer survivors, and (2) explore the association between pain-related fear avoidance and central sensitization symptoms. DESIGN: A single group pre-post intervention study was conducted. METHODS: Patients were recruited from the service of Medical Oncology of the University Clinical Hospital Virgen de la Victoria, in Málaga (Spain). The intervention consisted of a therapeutic exercise and educational program that lasted 12 weeks, twice a week, for 1 hour. Two instruments were used: the Spanish version of the Central Sensitization Inventory and the Spanish Fear Avoidance Components Scale. RESULTS: A total of 82 breast cancer survivors participated in the study. Pre-post change on Central Sensitization Inventory was statistically significant (p = .007). There was a trend towards a significant difference for the Spanish Fear Avoidance Components Scale (p = .062). There was a statistically significant correlation between pain-related fear avoidance and central sensitization symptoms (r = 0.536, p < .001). CONCLUSIONS: The current study has provided preliminary evidence on the benefits of this intervention in pain-related fear avoidance and central sensitization symptoms in breast cancer survivors. The Spanish version of the Central Sensitization Inventory and the Spanish Fear Avoidance Components Scale demonstrated responsiveness to change.

[Factors associated with an unfavorable evolution in patients diagnosed with COVID-19 and followed up in primary care in 2020]. / Factores asociados con una evolución desfavorable en pacientes diagnosticados de COVID-19 y seguidos en atención primaria en 2020.

AIM: To know the factors associated with an unfavorable evolution (UE) of patients diagnosed with COVID-19 with total or partial follow-up in primary care. DESIGN: A case series. SETTING: Urban health center. PARTICIPANTS: By systematic sampling, patients ≥18 years, diagnosed with COVID-19, with analytical confirmation, in 2020 and followed up by their family doctors, were selected. MAIN MEASUREMENTS: Dependent variable: hospital admission or death due to COVID-19. INDEPENDENT VARIABLES: age, sex, medical background, clinical data and treatments related to the disease. Statistical analysis, with SPSS 25.0: descriptive analysis, comparison of proportions (chi square) and medians (Mann-Whitney U). The analysis is completed with logistic regression. RESULTS: 610 patients were included in the study. The median age was 49 years (interquartile range: 35-61); 51.8% were women; 14.9% presented UE (95% CI: 12.0-17.8). The sociodemographic variables or the variables related to medical background that showed an independent association with UE were age (OR: 1.066; 95% CI: 1.038-1.095), sex (OR for men: 3.277; 95% CI: 1.304-8.235) and being a smoker or former smoker (OR: 2.565; 95% CI: 1.135-5.800). Regarding the clinical variables of the disease, an association was found for altered consciousness (OR: 62.829; 95% CI: 9.177-430.149), dyspnea (OR: 14.339; 95% CI: 6.046-34.009), expectoration (OR: 4.764; 95% CI: 1.858-12.213)) and asthenia (OR: 3.993; 95% CI: 1.705-9.351). CONCLUSIONS: 14.9% of the patients diagnosed with COVID-19 presented an UE. Older age, male sex and being a smoker or former smoker increased the probability of it. Altered consciousness, dyspnea, expectoration, and asthenia were the clinical data that best predicted UE.

The spread of SARS-CoV-2 in Spain: Hygiene habits, sociodemographic profile, mobility patterns and comorbidities.

COVID-19 constitutes the largest pandemic in the last 100 years. In view of the rapid spread of the virus, it is necessary to study the sociodemographic characteristics, hygiene habits, activity and mobility, and comorbidities of SARS-CoV-2 infection to be able to implement prevention strategies. For this purpose, a survey including the variables of interest was designed to try to understand the exponential spread of the virus despite the implemented severe restrictive mobility measures during the period of maximum confinement in Spain. This study conducted throughout the Spanish territory aims to clarify other routes of transmission of the COVID-19 during confinement, risk factors, and the effectiveness of the recommended hygiene measures to detect critical points of exposure to the virus and thus reduce its spread in this and possible future pandemics that could compromise public health. Our results show that living with a COVID-19 patient increased the risk of contagion by 60 times. Among all the sociodemographic variables analyzed, walking the dog have shown to have the strongest effect by increasing the risk by 78%. The most effective hygiene measure reducing the prevalence of the disease was the disinfection of products purchased from the market upon arrival home (which reduced the risk by 94%), above other hygiene measures, such as wearing masks, gloves, ethanol disinfection, bleaching and others. The mobility variable studied that showed the largest increase in the prevalence of the disease was working on site at the workplace (increased the risk by 76%). A significant higher prevalence of the disease was also detected among respondents who used the modality of acquiring basic commodities using home delivery service compared to those who chose in-store shopping.

Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort.

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.

Determine safety of outpatient chemotherapy and autotransplants using refrigerated, non-frozen grafts in persons with multiple sclerosis.

BACKGROUND: Persons with multiple sclerosis are increasingly treated with intermediate- or high-dose chemotherapy and a hematopoietic cell autotransplant. This is often done in an inpatient setting using frozen blood cell grafts. OBJECTIVE: Determine if chemotherapy and a hematopoietic cell autotransplant can be safely done in an outpatient setting using refrigerated, non-frozen grafts. METHODS: We developed an autotransplant protocol actionable in an outpatient setting using a refrigerated, non-frozen blood graft collected after giving cyclophosphamide, 50 mg/kg/d × 2 days and filgrastim, 10 µg/kg/d. A second identical course was given 9 days later followed by infusion of blood cells stored at 4°C for 1-4 days. The co-primary outcomes were rates of granulocyte and platelet recovery and therapy-related mortality. RESULTS: We treated 426 consecutive subjects. Median age was 47 years (range, 21-68 years). A total of 145 (34%) were male. Median graft refrigeration time was 1 day (range, 1-4 days). Median interval to granulocytes >0.5 × 10E + 9/L was 8 days (range, 2-12) and to platelets >20 × 10E + 9/L, 8 days (range, 1-12). Only 15 subjects (4%) were hospitalized, predominately for iatrogenic pneumothorax (N = 5) and neutropenic fever (N = 4). There was only 1 early death from infection. CONCLUSION: Intermediate-dose chemotherapy and a hematopoietic cell autotransplant can be safely done in an outpatient setting using, refrigerated, non-frozen grafts.

Disparities in the management of cutaneous malignant melanoma. A population-based high-resolution study.

Population-based cancer registry data from three Spanish areas were used to assess the patterns of care and adherence to guidelines for cutaneous malignant melanoma. We included 934 cases diagnosed in 2009-2013. Completeness of the pathology reports, imaging for detecting distant metastasis and the use of sentinel lymph node biopsy (SLNB) were analysed. The proportion of pathology reports that mentioned the essential pathological features required for T staging was 93%, ranging across geographic areas from 81% to 98% (p < 0.001). The percentage of low-risk patients who underwent no imaging studies, as proposed by guidelines, or only chest imaging ranged among areas from 0.6% to 84% (p < 0.001). Of the patients with clinically node-negative melanoma >1 mm thick and no distant metastases, 68% underwent SLNB, varying by area from 61% to 78% (p = 0.017). This study revealed wide geographic variation in different aspects of melanoma care. The use of a standardised structured pathology report could strengthen the completeness of reporting. Improvement strategies should also include efforts to reduce overuse of imaging in low-risk patients and to increase the adherence to guidelines recommendations on the use of SLNB.

Development or disease: duality of the mitochondrial permeability transition pore.

Mitochondria is not only a dynamic organelle that produces ATP, but is also an important contributor to cell functions in both development and cell death processes. These paradoxical functions of mitochondria are partially regulated by the mitochondrial permeability transition pore (mPTP), a high-conductance channel that can induce loss of mitochondrial membrane potential, impairment of cellular calcium homeostasis, oxidative stress, and a decrease in ATP production upon pathological activation. Interestingly, despite their different etiologies, several neurodegenerative diseases and heart ischemic injuries share mitochondrial dysfunction as a common element. Generally, mitochondrial impairment is triggered by calcium deregulation that could lead to mPTP opening and cell death. Several studies have shown that opening of the mPTP not only induces mitochondrial damage and cell death, but is also a physiological mechanism involved in different cellular functions. The mPTP participates in regular calcium-release mechanisms that are required for proper metabolic regulation; it is hypothesized that the transient opening of this structure could be the principal mediator of cardiac and brain development. The mPTP also plays a role in protecting against different brain and cardiac disorders in the elderly population. Therefore, the aim of this work was to discuss different studies that show this controversial characteristic of the mPTP; although mPTP is normally associated with several pathological events, new critical findings suggest its importance in mitochondrial function and cell development.

The Josephson heat interferometer.

The Josephson effect is perhaps the prototypical manifestation of macroscopic phase coherence, and forms the basis of a widely used electronic interferometer--the superconducting quantum interference device (SQUID). In 1965, Maki and Griffin predicted that the thermal current through a temperature-biased Josephson tunnel junction coupling two superconductors should be a stationary periodic function of the quantum phase difference between the superconductors: a temperature-biased SQUID should therefore allow heat currents to interfere, resulting in a thermal version of the electric Josephson interferometer. This phase-dependent mechanism of thermal transport has been the subject of much discussion but, surprisingly, has yet to be realized experimentally. Here we investigate heat exchange between two normal metal electrodes kept at different temperatures and tunnel-coupled to each other through a thermal 'modulator' (ref. 5) in the form of a direct-current SQUID. We find that heat transport in the system is phase dependent, in agreement with the original prediction. Our Josephson heat interferometer yields magnetic-flux-dependent temperature oscillations of up to 21 millikelvin in amplitude, and provides a flux-to-temperature transfer coefficient exceeding 60 millikelvin per flux quantum at 235 millikelvin. In addition to confirming the existence of a phase-dependent thermal current unique to Josephson junctions, our results point the way towards the phase-coherent manipulation of heat in solid-state nanocircuits.

Coffee Drinking and Mortality in 10 European Countries: A Multinational Cohort Study.

BACKGROUND: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear. OBJECTIVE: To examine whether coffee consumption is associated with all-cause and cause-specific mortality. DESIGN: Prospective cohort study. SETTING: 10 European countries. PARTICIPANTS: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition). MEASUREMENTS: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800). RESULTS: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; γ-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels. LIMITATIONS: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once. CONCLUSION: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country. PRIMARY FUNDING SOURCE: European Commission Directorate-General for Health and Consumers and International Agency for Research on Cancer.

Thoracic Changes after Full Laser Ablation of the Feeding Artery in Fetuses with Bronchopulmonary Sequestration.

OBJECTIVE: To assess longitudinal intrathoracic changes after fetal laser surgery in fetuses with bronchopulmonary sequestration (BPS) with hydrops and/or hydrothorax. STUDY DESIGN: The presence of intrafetal fluid effusions, the lung mass volume ratio (congenital pulmonary airway malformation volume ratio [CVR]), and the observed/expected lung-to-head circumference ratio (O/E-LHR) of both lungs were evaluated in a cohort of BPS fetuses with hydrops and/or hydrothorax treated with full laser ablation of the feeding artery (FLAFA). The longitudinal changes in intrafetal fluid effusions, lung mass volume, and pulmonary growth were analyzed by survival and multilevel analysis against days after FLAFA. RESULTS: FLAFA was successfully performed in 15 cases at a median gestational age of 26.9 weeks. A complete disappearance of the hydrops and hydrothorax was observed a median interval of 7.5 and 21 days after the fetal intervention, respectively. A progressive decrease in the CVR and an increment in the size of both lungs were observed after FLAFA. The O/E-LHR of the lung contralateral and ipsilateral to the side of the BPS became normal on average 8 and 10 weeks after FLAFA, respectively. CONCLUSION: Fetal laser surgery with FLAFA promotes disappearance of all fetal fluid effusions, a lung mass regression sequence, and a normalization of pulmonary growth.

Possible role of mitochondrial permeability transition pore in the pathogenesis of Huntington disease.

Huntington disease (HD) is a devastating neurological disorder that affects the striatum and cortex of patients. HD patients develop progressive motor dysfunction and psychiatric disturbances with gradual dementia. HD is caused by a pathological expansion of CAG repeats in the huntingtin gene that codifies for a protein called huntingtin (Htt), which principal function is not completely understood. Accumulative evidence shows that this pathological expansion modifies Htt function affecting different neuronal targets, including mitochondrial function which is an important factor that contributes to HD. Interestingly, several groups have shown mitochondrial disturbances including calcium handling defects, depolarization, decrease of mitochondrial transport, ATP reduction, and increase of reactive oxygen species (ROS) in cellular and murine HD models. Systematic analysis of this evidence indicates that a mitochondrial structure, the mitochondrial permeability transition pore (mPTP), could be responsible for these changes that affect mitochondria. The mPTP plays an important role in apoptosis and neurodegeneration. It has also been reported to have some physiological functions in heart development and synaptic communication. In HD, the presence of mutant huntingtin (mHtt) activates this mechanism producing a significant compromise of mitochondrial metabolism and bioenergetics. Considering these findings this review explores the evidence that suggests the important role of mPTP in the mitochondrial impairment induced by mHtt, which leads to calcium derangement and contributes to neuronal dysfunction in HD.

Malondialdehyde as a Prognostic Factor in Alcoholic Hepatitis.

AIMS: Alcoholic hepatitis is a severe complication of alcoholism, associated with high short-term mortality. Although pathogenesis remains obscure, it is generally accepted that lipopolysaccharide-induced cytokine secretion with further generation of reactive oxygen species (ROS) play outstanding roles. Prognosis is uncertain, and the usually employed prognostic scores do not include variables related to ROS generation. Therefore, this study was performed to assess short-term prognostic value of cytokines, nutritional status, different scores [Maddrey, model for end-stage liver disease (MELD), albumin, bilirubin, INR, creatinine index (ABIC), Lille, Glasgow, MELD-Na, Child-Pugh] and malondialdehyde (MDA, as an indicator of lipid peroxidation) at admission and after 1 week, among patients affected by severe acute alcoholic hepatitis (Maddrey index >32). METHODS: Sixty-two patients affected by severe acute alcoholic hepatitis, for whom we calculated Maddrey, MELD, ABIC, Lille, Glasgow, MELD-Na, Child-Pugh, and determined serum MDA and interleukin (IL)-6, IL-8, IL-4, tumor necrosis factor alpha and interferon gamma levels at admission and after 1 week. RESULTS: Twenty-four patients died during the follow-up period. MDA showed a better prognostic accuracy than the aforementioned scores, both at admission and after 1 week. CONCLUSION: Our study supports the importance of including MDA assessment in the prognostic evaluation of patients with alcoholic hepatitis. SHORT SUMMARY: Alcoholic hepatitis is associated with high short-term mortality. Although not included in prognostic scores, lipid peroxidation plays an outstanding role in its pathogenesis. We found that malondialdehyde levels showed a better prognostic accuracy than the usually employed scores. Therefore, it should be included in the prognostic evaluation of these patients.

Evidence of Benefit of Telerehabitation After Orthopedic Surgery: A Systematic Review.

BACKGROUND: In addition to traditional physiotherapy, studies based on telerehabilitation programs have published the results of effectiveness, validity, noninferiority, and important advantages in some neurological, cognitive, and musculoskeletal disorders, providing an opportunity to define new social policies and interventions. OBJECTIVES: The aim of this systematic review is to investigate the effects of telerehabilitation after surgical procedures on orthopedic conditions as well as to describe how interventions are designed and to determine whether telerehabilitation is comparable with conventional methods of delivery. This systematic review summarizes the levels of evidence and grades of recommendation regarding telerehabilitation intervention (synchronous or asynchronous provided via the telerehabilitation medium, either in conjunction with, or in isolation of, other treatment interventions) after surgical procedures on orthopedic conditions. METHODS: Study quality was assessed using the Physiotherapy Evidence Database (PEDro) scores and grade of recommendation following the recommendation of the Oxford Centre for Evidence-Based Medicine. RESULTS: We found 3 studies with PEDro scores between 6 and 8, which is considered as level 1 evidence (good; 20% [3/15]), 4 studies with a score of 5, which is considered as level 2 evidence (acceptable; 27% [4/15]), and the remaining 8 studies had scores of 4 or less, which is considered (poor; 53% [8/15]). A total of 1316 participants received telerehabilitation intervention in the selected studies, where knee and hip replacement were 75% of all the studies. Strong and moderate grades of evidence (grade of recommendation A-B) were found in knee and hip replacement interventions. Studies on the upper limb were 25% of the studies, but only 1 study presented a moderate grade of evidence (grade of recommendation B) and the rest were of poor methodological quality with weak evidence (grade of recommendation C). CONCLUSIONS: Conclusive evidence on the efficacy of telerehabilitation for treatment after an orthopedic surgery, regardless of pathology, was not obtained. We found strong evidence in favor of telerehabilitation in patients following total knee and hip arthroplasty and limited evidence in the upper limb interventions (moderate and weak evidence). Future research needs to be more extensive and conclusive. To the best of the authors' knowledge, this is the first attempt at evaluating the quality of telerehabilitation intervention research after surgical procedures on orthopedic conditions in a systematic review. Clinical messages and future research recommendations are included in the review.

Antimicrobial Action of Compounds from Marine Seaweed.

Seaweed produces metabolites aiding in the protection against different environmental stresses. These compounds show antiviral, antiprotozoal, antifungal, and antibacterial properties. Macroalgae can be cultured in high volumes and would represent an attractive source of potential compounds useful for unconventional drugs able to control new diseases or multiresistant strains of pathogenic microorganisms. The substances isolated from green, brown and red algae showing potent antimicrobial activity belong to polysaccharides, fatty acids, phlorotannins, pigments, lectins, alkaloids, terpenoids and halogenated compounds. This review presents the major compounds found in macroalga showing antimicrobial activities and their most promising applications.

Bacillus aryabhattai BA03: a novel approach to the production of natural value-added compounds.

A strain designated as BA03, with the ability to transform ferulic acid into vanillin and 4-vinylguaiacol, was isolated from contaminated cryovials. The production of natural value-added compounds was dependent on the media employed. The morphological and physiological characteristics of this strain were compared with those of the typical vanillin-producer strain Amycolatopsis sp. ATCC 39116. According to a partial 16S rRNA sequence, we determined that BA03 belonged to Bacillus aryabhattai. In addition, analysis of the results showed that this strain exhibited interesting enzymatic activity, including cellulases, laccases, lipases and pectinases. In light of this, we propose new functions for this multitasking microorganism. We suggest that it may be used for converting lignocellulosic wastes into byproducts with industrial uses, and also for treating disposal residues such as dyes in the textile industry. Hence, the possibility for novel research with B. aryabhattai opens up in the fields of biodegradation and/or revalorization of wastes.

Coffee and tea consumption and risk of pre- and postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study.

INTRODUCTION: Specific coffee subtypes and tea may impact risk of pre- and post-menopausal breast cancer differently. We investigated the association between coffee (total, caffeinated, decaffeinated) and tea intake and risk of breast cancer. METHODS: A total of 335,060 women participating in the European Prospective Investigation into Nutrition and Cancer (EPIC) Study, completed a dietary questionnaire from 1992 to 2000, and were followed-up until 2010 for incidence of breast cancer. Hazard ratios (HR) of breast cancer by country-specific, as well as cohort-wide categories of beverage intake were estimated. RESULTS: During an average follow-up of 11 years, 1064 premenopausal, and 9134 postmenopausal breast cancers were diagnosed. Caffeinated coffee intake was associated with lower risk of postmenopausal breast cancer: adjusted HR=0.90, 95% confidence interval (CI): 0.82 to 0.98, for high versus low consumption; Ptrend=0.029. While there was no significant effect modification by hormone receptor status (P=0.711), linear trend for lower risk of breast cancer with increasing caffeinated coffee intake was clearest for estrogen and progesterone receptor negative (ER-PR-), postmenopausal breast cancer (P=0.008). For every 100 ml increase in caffeinated coffee intake, the risk of ER-PR- breast cancer was lower by 4% (adjusted HR: 0.96, 95% CI: 0.93 to 1.00). Non-consumers of decaffeinated coffee had lower risk of postmenopausal breast cancer (adjusted HR=0.89; 95% CI: 0.80 to 0.99) compared to low consumers, without evidence of dose-response relationship (Ptrend=0.128). Exclusive decaffeinated coffee consumption was not related to postmenopausal breast cancer risk, compared to any decaffeinated-low caffeinated intake (adjusted HR=0.97; 95% CI: 0.82 to 1.14), or to no intake of any coffee (HR: 0.96; 95%: 0.82 to 1.14). Caffeinated and decaffeinated coffee were not associated with premenopausal breast cancer. Tea intake was neither associated with pre- nor post-menopausal breast cancer. CONCLUSIONS: Higher caffeinated coffee intake may be associated with lower risk of postmenopausal breast cancer. Decaffeinated coffee intake does not seem to be associated with breast cancer.