53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination.

53BP1 activity drives genome instability and lethality in BRCA1-deficient mice by inhibiting homologous recombination (HR). The anti-recombinogenic functions of 53BP1 require phosphorylation-dependent interactions with PTIP and RIF1/shieldin effector complexes. While RIF1/shieldin blocks 5'-3' nucleolytic processing of DNA ends, it remains unclear how PTIP antagonizes HR. Here, we show that mutation of the PTIP interaction site in 53BP1 (S25A) allows sufficient DNA2-dependent end resection to rescue the lethality of BRCA1Δ11 mice, despite increasing RIF1 "end-blocking" at DNA damage sites. However, double-mutant cells fail to complete HR, as excessive shieldin activity also inhibits RNF168-mediated loading of PALB2/RAD51. As a result, BRCA1Δ1153BP1S25A mice exhibit hallmark features of HR insufficiency, including premature aging and hypersensitivity to PARPi. Disruption of shieldin or forced targeting of PALB2 to ssDNA in BRCA1D1153BP1S25A cells restores RNF168 recruitment, RAD51 nucleofilament formation, and PARPi resistance. Our study therefore reveals a critical function of shieldin post-resection that limits the loading of RAD51.

A mouse model for Li-Fraumeni-Like Syndrome with cardiac angiosarcomas associated to POT1 mutations.

The shelterin protein POT1 has been found mutated in many different familial and sporadic cancers, however, no mouse models to understand the pathobiology of these mutations have been developed so far. To address the molecular mechanisms underlying the tumorigenic effects of POT1 mutant proteins in humans, we have generated a mouse model for the human POT1R117C mutation found in Li-Fraumeni-Like families with cases of cardiac angiosarcoma by introducing this mutation in the Pot1a endogenous locus, knock-in for Pot1aR117C. We find here that both mouse embryonic fibroblasts (MEFs) and tissues from Pot1a+/ki mice show longer telomeres than wild-type controls. Longer telomeres in Pot1a+/ki MEFs are dependent on telomerase activity as they are not found in double mutant Pot1a+/ki Tert-/- telomerase-deficient MEFs. By using complementation assays we further show that POT1a pR117C exerts dominant-negative effects at telomeres. As in human Li-Fraumeni patients, heterozygous Pot1a+/ki mice spontaneously develop a high incidence of angiosarcomas, including cardiac angiosarcomas, and this is associated to the presence of abnormally long telomeres in endothelial cells as well as in the tumors. The Pot1a+/R117C mouse model constitutes a useful tool to understand human cancers initiated by POT1 mutations.

iMS-Bmal1-/- mice show evident signs of sarcopenia that are counteracted by exercise and melatonin therapies.

Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in Bmal1 clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible Bmal1 knockout mice (iMS-Bmal1-/- ) were examined by phenotypic tests and light and electron microscopy. Our results revealed a disruption of the normal activity/rest rhythm, a drop in skeletal muscle function and mass, and increased frailty in male and female iMS-Bmal1-/- animals compared to controls. A reduction in muscle fiber size and increased collagenous tissue were also detected, accompanied by reduced mitochondrial oxidative capacity and a compensatory shift towards a more oxidative fiber type. Electron microscopy further supports mitochondrial impairment in mutant mice. Melatonin and exercise ameliorated the damage caused by loss of Bmal1 in mutant mice, except for mitochondrial damage, which was worsened by the latter. Thus, iMS-Bmal1-/- mice let us to identify Bmal1 deficiency as the responsible for the appearance of sarcopenia in the gastrocnemius muscle. Moreover, the results support the exercise and melatonin as therapeutic tools to counteract sarcopenia, by a mechanism that does not require the presence of Bmal1.

AKT-dependent signaling of extracellular cues through telomeres impact on tumorigenesis.

The telomere-bound shelterin complex is essential for chromosome-end protection and genomic stability. Little is known on the regulation of shelterin components by extracellular signals including developmental and environmental cues. Here, we show that human TRF1 is subjected to AKT-dependent regulation. To study the importance of this modification in vivo, we generate knock-in human cell lines carrying non-phosphorylatable mutants of the AKT-dependent TRF1 phosphorylation sites by CRISPR-Cas9. We find that TRF1 mutant cells show decreased TRF1 binding to telomeres and increased global and telomeric DNA damage. Human cells carrying non-phosphorylatable mutant TRF1 alleles show accelerated telomere shortening, demonstrating that AKT-dependent TRF1 phosphorylation regulates telomere maintenance in vivo. TRF1 mutant cells show an impaired response to proliferative extracellular signals as well as a decreased tumorigenesis potential. These findings indicate that telomere protection and telomere length can be regulated by extracellular signals upstream of PI3K/AKT activation, such as growth factors, nutrients or immune regulators, and this has an impact on tumorigenesis potential.

Zebrafish as a Human Muscle Model for Studying Age-Dependent Sarcopenia and Frailty.

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index with a value of 0.250 ± 0.000 because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes (0.031 myocytes/µm2 ± 0.004 at 60 months) and an increase in collagen with aging up to 15% ± 1.639 in the 60-month group, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a nearly 50% reduction in the number of intermyofibrillar mitochondria, 100% mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.

The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease.

Early diagnosis and treatment of chronic kidney disease (CKD) is a worldwide challenge. Subjects with albumin-to-creatinine ratio (ACR) ≥ 30 mg/g and preserved renal function are considered to be at no cardiorenal risk in clinical practice, but prospective clinical studies evidence increased risk, even at the high-normal (HN) ACR range (10-30 mg/g), supporting the need to identify other molecular indicators for early assessment of patients at higher risk. Following our previous studies, here we aim to stratify the normoalbuminuria range according to cardiorenal risk and identify the glycoproteins and N-glycosylation sites associated with kidney damage in subclinical CKD. Glycoproteins were analyzed in urine from hypertensive patients within the HN ACR range compared to control group (C; ACR < 10 mg/g) by mass spectrometry. A different cohort was analyzed for confirmation (ELISA) and sex perspective was evaluated. Patients' follow-up for 8 years since basal urine collection revealed higher renal function decline and ACR progression for HN patients. Differential N-glycopeptides and their N -glycosylation sites were also identified, together with their pathogenicity. N-glycosylation may condition pathological protein deregulation, and a panel of 62 glycoproteins evidenced alteration in normoalbuminuric subjects within the HN range. Haptoglobin-related protein, haptoglobin, afamin, transferrin, and immunoglobulin heavy constant gamma 1 (IGHG1) and 2 (IGHG2) showed increased levels in HN patients, pointing to disturbed iron metabolism and tubular reabsorption and supporting the tubule as a target of interest in the early progression of CKD. When analyzed separately, haptoglobin, afamin, transferrin, and IGHG2 remained significant in HN, in both women and men. At the peptide level, 172 N-glycopeptides showed differential abundance in HN patients, and 26 showed high pathogenicity, 10 of them belonging to glycoproteins that do not show variation between HN and C groups. This study highlights the value of glycosylation in subjects not meeting KDIGO criteria for CKD. The identified N-glycopeptides and glycosylation sites showed novel targets, for both the early assessment of individual cardiorenal risk and for intervention aimed at anticipating CKD progression.

Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy.

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.

The association between levator plate integrity and pelvic floor defaecatory dysfunction.

AIMS: Levator ani deficiency has been implicated in anterior pelvic floor pathology but its association with pelvic floor defaecatory dysfunction is less clear. The aim was to examine the relationship of levator ani deficiency with anatomical abnormalities (rectocoele, intussusception, enterocoele, perineal descent) and patient symptoms (bowel, vagina) in patients with pelvic floor defaecatory dysfunction. METHODS: The prospective observational case series of 223 women presenting to a tertiary colorectal pelvic floor unit with defaecatory dysfunction. Each underwent assessment with symptom severity and quality of life (QoL) scores, integrated total pelvic floor ultrasound (PFUS) (transvaginal, transperineal) and defaecation proctography (DP). Rectocoele, intussusception, enterocoele and perineal descent were assessed on both. Levator ani deficiency was scored using endovaginal ultrasound (score 0-18; mild [0-6], moderate [>6-12], severe [>12-18]). RESULTS: The proportion of patients with rectocoele, enterocoele, and intussusception increased with increasing levator ani damage (mild, moderate, severe). There was a weakly positive correlation between size of rectocoele and levator ani deficiency. On PFUS, there was a weakly positive correlation between severity of intussusception and enterocoele with levator ani deficiency. On DP, there was a weakly positive correlation between perineal descent and levator ani deficiency. There was no association between bowel symptom and QoL scores and levator ani deficiency. Vaginal symptoms were associated with levator ani deficiency. CONCLUSIONS: Anatomical abnormalities which are implicated in pelvic floor defaecatory dysfunction (rectocoele, intussusception, enterocoele, perineal descent) were associated with worsening levator ani deficiency. There was no association between bowel symptoms and levator ani deficiency. Vaginal symptoms were associated with levator ani deficiency.

Psychotropic consumption before and during COVID-19 in Asturias, Spain.

BACKGROUND: Spain as multiple other countries has been experiencing an increasing and sustained trend in the use of psychotropic medications since the mid 90s. Recent studies show public health measures implemented to control SARS-Cov2, such as mobility restrictions and the shutdown of nonessential activities increased mental suffering, even contributing to a higher number of anxiety, depression and insomnia disorders that could lead to an increase in the consumption of psychotropics. The aims were: 1) Evaluate the temporal trend in psychotropic consumption by pharmacological subgroup, sex, and age group 2) Estimate the effect of the COVID-19 pandemic in the use of psychotropic drugs. METHODS: We conducted a retrospective observational study, retrieving all prescriptions of anxiolytics, hypnotics and sedatives, and antidepressants dispensed in pharmacies of Asturias (Northern Spain) for Primary Care patients for the period 2018-2021. We presented the data expressed in Daily Defined Doses (DDDs) for 1000 persons/day (DHD). To estimate changes in DHDs by year and age group we conducted two multiple linear regressions (one for males and one for females) for every pharmacological subgroup studied. Changes were considered statistically significant when the regression coefficient was p < 0.05. We used the Software R 4.1.0. RESULTS: For the studied period, the highest DHDs are for antidepressants, although all of the subgroups experienced an increase in consumption rates. Women consumed more psychotropic drugs than men. In 2021, 372 out of every 1000 women were taking daily 1 DDD of these drugs versus 184 out of every 1000 men. Consumption rates for all psychotropic drugs progressively increases with age. Conversely, the biggest increases in consumption were among the youngest age groups (0-14 and 15-29 years) for women, while for men there is more variability. The regression models suggest an upward trend in psychotropic consumption during all the period, especially remarkable from 2020, for both genders and all age groups. CONCLUSIONS: - The consumption of psychotropic drugs has gradually increased over the last 4 years, with a significant boost starting in 2020 for both sexes, matching the start of the SARS-COV2 pandemic and the implementation of strict Public Health measures to contain it. - The increase observed on children and adolescents is a matter of concern.

Dy4, Dy5, and Ho2 Complexes of an N3O2 Aminophenol Donor: A Dy5-µ3-Peroxide Single Molecule Magnet.

The reactivity of the new flexible potentially pentadentate N3O2 aminophenol ligand H4Lr (2,2'-((pyridine-2,6-diylbis(methylene))bis(azanediyl))diphenol) towards different dysprosium salts and holmium(III) nitrate was investigated. Accordingly, this reactivity seems to greatly depend on the metal ion and salt employed. In this way, the reaction of H4Lr with dysprosium(III) chloride in air leads to the oxo-bridged tetranuclear complex [Dy4(H2Lr)3(Cl)4(µ3-O)(EtOH)2(H2O)2]·2EtOH·H2O (1·2EtOH·H2O), while the same reaction just changing the chloride salt by the nitrate one renders the peroxo-bridged pentanuclear compound [Dy5(H2Lr)2(H2.5Lr)2(NO3)4(µ3-O2)2]·2H2O (2·2H2O), where both peroxo ligands seem to come from the fixation and reduction of atmospheric oxygen. However, if holmium(III) nitrate is used instead of dysprosium(III) nitrate, no evidence of a peroxide ligand is observed, and the dinuclear complex {[Ho2(H2Lr)(H3Lr)(NO3)2(H2O)2](NO3)} 2.5H2O (3·2.5H2O) is isolated. The three complexes were unequivocally characterized by X-ray diffraction techniques, and their magnetic properties were analyzed. Thus, while the Dy4 and Ho2 complexes do not show magnet-like behavior even in the presence of an external magnetic field, 2·2H2O is a single molecule magnet, with an Ueff barrier of 61.2 K (43.2 cm-1). This is the first homonuclear lanthanoid peroxide SMM, which also shows the highest barrier among the reported 4f/3d peroxide zero field SMMs to date.

[Impact of COVID-19 lockdown on the prescription of benzodiazepines]. / Impacto del confinamiento por COVID-19 en la prescripción de benzodiacepinas.

OBJECTIVE: To evaluate the effect of COVID-19 lockdown on the prescription of benzodiazepines by gender, age and district health departments. DESIGN: Longitudinal observational study. LOCATION: Primary care. Asturias (Spain) health district V. PARTICIPANTS: People over 15 years of age with filled benzodiazepine prescriptions in between 2017 and 2020. MAIN MEASUREMENTS: Benzodiazepine DHD (defined daily dose per 1000 habitants) mean difference between the period defined as pre-lockdown and lockdown. Additionally, the difference was adjusted for gender, sex and district health department and also with the interaction among them. RESULTS: DHD mean pre-lockdown was 131.3 and 139.5 in the lockdown; this difference was significant in the global analysis (95% CI: 4.1-12.1). There was an increase in the DHD mean in the 60-74 age group (95% CI: 2.28-21.42), in the group over 90 years old (95% CI: 21.31-40.63) and in women (95% CI: 3.51-14.59). Finally, a decrease in the DHD mean of V11 (95% CI: -29 to -0.66) and V14 (95% CI: -54.28 to -25.04) district health departments was observed. CONCLUSIONS: Certain subgroups show a change in the pattern of benzodiazepine prescription without being able to relate this to the lockdown. We believe that there could be some inertia in the prescription of psychiatric medication according to the biopsychosocial characteristics of the patients; it is important to detect this in order to avoid the medicalization of psychological disorders.

Why don't we share data and code? Perceived barriers and benefits to public archiving practices.

The biological sciences community is increasingly recognizing the value of open, reproducible and transparent research practices for science and society at large. Despite this recognition, many researchers fail to share their data and code publicly. This pattern may arise from knowledge barriers about how to archive data and code, concerns about its reuse, and misaligned career incentives. Here, we define, categorize and discuss barriers to data and code sharing that are relevant to many research fields. We explore how real and perceived barriers might be overcome or reframed in the light of the benefits relative to costs. By elucidating these barriers and the contexts in which they arise, we can take steps to mitigate them and align our actions with the goals of open science, both as individual scientists and as a scientific community.

Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer.

Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer (BC), accounting for up to 15% of all invasive BC. Loss of cell adhesion due to functional inactivation of E-cadherin is the hallmark of ILC. Although the current world health organization (WHO) classification for diagnosing ILC requires the recognition of the dispersed or linear non-cohesive growth pattern, it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC). Recent results of central pathology review of two large randomized clinical trials have demonstrated relative overdiagnosis of ILC, as only ~60% of the locally diagnosed ILCs were confirmed by central pathology. To understand the possible underlying reasons of this discrepancy, we undertook a worldwide survey on the current practice of diagnosing BC as ILC. A survey was drafted by a panel of pathologists and researchers from the European lobular breast cancer consortium (ELBCC) using the online tool SurveyMonkey®. Various parameters such as indications for IHC staining, IHC clones, and IHC staining procedures were questioned. Finally, systematic reporting of non-classical ILC variants were also interrogated. This survey was sent out to pathologists worldwide and circulated from December 14, 2020 until July, 1 2021. The results demonstrate that approximately half of the institutions use E-cadherin expression loss by IHC as an ancillary test to diagnose ILC and that there is a great variability in immunostaining protocols. This might cause different staining results and discordant interpretations. As ILC-specific therapeutic and diagnostic avenues are currently explored in the context of clinical trials, it is of importance to improve standardization of histopathologic diagnosis of ILC diagnosis.

Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport.

The oncostatic effects of melatonin correlate with increased reactive oxygen species (ROS) levels, but how melatonin induces this ROS generation is unknown. In the present study, we aimed to elucidate the two seemingly opposing actions of melatonin regarding its relationship with free radicals. We analyzed the effects of melatonin on head and neck squamous cell carcinoma cell lines (Cal-27 and SCC-9), which were treated with 0.5 or 1 mM melatonin. We further examined the potential effects of melatonin to induce ROS and apoptosis in Cal-27 xenograft mice. Here we report that melatonin mediates apoptosis in head and neck cancer by driving mitochondrial reverse electron transport (RET) to induce ROS production. Melatonin-induced changes in tumoral metabolism led to increased mitochondrial activity, which, in turn, induced ROS-dependent mitochondrial uncoupling. Interestingly, mitochondrial complex inhibitors, including rotenone, abolished the ROS elevation indicating that melatonin increased ROS generation via RET. Melatonin also increased membrane potential and CoQ10 H2 /CoQ10 ratio to elevate mitochondrial ROS production, which are essential conditions for RET. We found that genetic manipulation of cancer cells with alternative oxidase, which transfers electrons from QH2 to oxygen, inhibited melatonin-induced ROS generation, and apoptosis. RET restored the melatonin-induced oncostatic effect, highlighting the importance of RET as the site of ROS production. These results illustrate that RET and ROS production are crucial factors in melatonin's effects in cancer cells and establish the dual effect of melatonin in protecting normal cells and inducing apoptosis in cancer cells.

Colorectal cancer survival: prevalence of psychosocial distress and unmet supportive care needs.

PURPOSE: The aim of this study was to determine the prevalence of distress and unmet supportive care needs in post-treatment colorectal cancer (CRC) survivors. Also, to explore the association between both variables and to identify potential associated sociodemographic and cancer-related risk factors. METHODS: A cross-sectional study of 200 CRC survivors who at least 1 month before had completed the primary treatment for CRC was conducted. The Brief Symptom Inventory-18 (BSI-18) and the Spanish version of Cancer Survivors' Unmet Needs (S-CaSUN) were used. RESULTS: One in five CRC survivors showed clinical distress and 86% expressed at least one unmet need. Distress was positively associated with the prevalence of needs in all domains. All comprehensive care and information needs were expressed by at least 20% of survivors and some by more than 50%. Other needs also mentioned by 20% of survivors were financial support, ongoing case manager, and concerns about cancer recurrence. The risk factors associated were lower socioeconomic status, younger age, and a primary treatment that includes more than surgery. CONCLUSIONS: The findings highlight the relevance of extending psychosocial care beyond the CRC primary medical treatment. A person-centered approach that addresses informational, emotional, social, and physical needs can increase satisfaction with care and also prevent psychological morbidity in CRC survivors.

Anal endosonographic assessment of the accuracy of clinical diagnosis of obstetric anal sphincter injury.

INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injuries (OASIS) are a common cause of maternal morbidity with an overall incidence in the UK of 2.9% (range 0-8%). They can cause a range of physical symptoms and psychological distress. This study aims to assess the accuracy of clinical diagnosis of OASIS using endoanal ultrasound (EAUS) and the correlation between confirmed injury and change to anorectal physiology squeeze pressure and the incidence of bowel symptoms. METHODS AND MATERIALS: Retrospective study of prospectively collected data from 1135 women who attended the Third- and Fourth-Degree Tears Clinic at our institution, 12 weeks post-delivery, between June 2008 and October 2019. RESULTS: OASIS was confirmed in 876 (78.8%) women and 236 (21.3%) had no injury. Of the women who underwent anorectal physiology, 45.6% had a mean maximal resting pressure below the normal range and 68.8% had a mean incremental squeeze pressure below normal. Women with confirmed OASIS had significantly lower pressures (p < 0.001) than those without a confirmed sphincter injury. Three hundred ninety-three (34.8%) women reported bowel symptoms, with those with endosonographic evidence of injury more likely to develop flatus incontinence. CONCLUSION: Of the women in this study with a suspected OASIS, 21.2% could be reassured that they did not have an injury. This information is useful for women considering future mode of delivery. Those with confirmed injury are more likely to complain of flatus incontinence and have reduced anal sphincter pressures.

Effectiveness of aquatic exercise in the treatment of inflammatory arthritis: systematic review.

Spondyloarthritis and rheumatoid arthritis are classified as inflammatory arthritis and represent a significant source of pain and disability. Non-pharmacological intervention with physical exercise is among the therapeutic approaches most used by health professionals. This study aimed to investigate the effectiveness of aquatic exercise in the treatment of inflammatory arthritis. The review was registered on the PROSPERO (CRD42020189602). The databases (PubMed, PEDro, Web of Science, and SciELO) were searched for studies involving adults with inflammatory arthritis and subjected to rehabilitation with aquatic exercise compared to any other control group, from the year 2010 to March 2022. Pain, disease activity, and physical function were regarded as primary outcomes. Two reviewers completed the eligibility screening and data extraction, and disagreements were resolved by a third reviewer. The methodological quality was assessed using the PEDro scale. A total of 5254 studies were identified, and nine articles were included, totalling 604 participants. Regarding pain, two studies showed that aquatic exercise was superior to home exercise. One study showed that disease activity was significantly improved in the aquatic group compared to the land-based exercise and the control groups (no exercise). Two studies reported that therapy containing aquatic exercise was able to improve physical function. Overall, the studies included in this review indicate that aquatic exercise is effective in treating pain, disease activity, and physical function in individuals with inflammatory arthritis. However, further studies carrying stronger evidence should be conducted to determine whether the treatment with aquatic exercise is superior to other types of therapies.

Quality of life in cancer survivorship: Sociodemographic and disease-related moderators.

RATIONALE: To identify high-risk survivors in order to provide appropriate care. PURPOSE: To analyse the quality of life (QOL) of cancer survivors using an instrument designed specifically for this population and considering different sociodemographic and disease-related characteristics as possible modulating variables. METHODS: The Quality of Life in Adult Cancer Survivors (QLACS) was filled out by a large and heterogeneous sample of disease-free post-treatment Spanish cancer survivors (N = 1862). RESULTS: QLACS scores were comparable to those obtained in other studies and indicative of worse QOL as a function of shorter elapsed time since the end of primary treatment. The best QOL was shown by prostate, and the worst by hematologic cancer survivors. Both systemic treatments (chemotherapy and hormone therapy) and the combination of radiotherapy and chemotherapy were associated with worse QOL. Likewise, younger age, female sex, unemployment status and not having a stable partner were associated with worse QOL. CONCLUSION: Greater understanding of the QOL experienced by the already large and continuously growing population of cancer survivors is relevant for guiding both clinical practice and health policy. In addition, knowing the risk factors associated with worse QOL facilitates the development of targeted prevention programmes for those survivors who need it the most.

The Zebrafish, an Outstanding Model for Biomedical Research in the Field of Melatonin and Human Diseases.

The zebrafish has become an excellent model for the study of human diseases because it offers many advantages over other vertebrate animal models. The pineal gland, as well as the biological clock and circadian rhythms, are highly conserved in zebrafish, and melatonin is produced in the pineal gland and in most organs and tissues of the body. Zebrafish have several copies of the clock genes and of aanat and asmt genes, the latter involved in melatonin synthesis. As in mammals, melatonin can act through its membrane receptors, as with zebrafish, and through mechanisms that are independent of receptors. Pineal melatonin regulates peripheral clocks and the circadian rhythms of the body, such as the sleep/wake rhythm, among others. Extrapineal melatonin functions include antioxidant activity, inducing the endogenous antioxidants enzymes, scavenging activity, removing free radicals, anti-inflammatory activity through the regulation of the NF-κB/NLRP3 inflammasome pathway, and a homeostatic role in mitochondria. In this review, we introduce the utility of zebrafish to analyze the mechanisms of action of melatonin. The data here presented showed that the zebrafish is a useful model to study human diseases and that melatonin exerts beneficial effects on many pathophysiological processes involved in these diseases.

Quinoa protein extract: an effective alternative for the fining of wine phenolics.

BACKGROUND: Lately, there has been an increasing interest in using plant-derived proteins for wine phenolic fining. Proteins extracted from cereals, potatoes, and legumes have been proposed as effective fining agents, but only those from pea, wheat, and potatoes have been approved for their use in wine. This work aimed at determining the fining ability of quinoa (Chenopodium quinoa Willd.) protein extracts (QP), compared to commercial fining agents, on red wines. RESULTS: The trials compared the performance of QP (30 and 50 g/hL), two potato protein extracts and gelatin, at two different contact times (48 and 96 h), using Petit Verdot, Malbec, and Cabernet Sauvignon wines. Turbidity, total phenolics, precipitable tannins, catechins, and color characteristics were determined. QP reduced the turbidity of all wines in a similar way to commercial fining agents. Both doses of QP significantly reduced tannins and other phenolic measures, including color intensity reductions, in a similar way to commercial fining agents. CONCLUSION: QP behaved as an effective fining agent that deserves further studies in order to improve its performance and advance its characterization. © 2022 Society of Chemical Industry.