Association of molecular senescence markers in late-life depression with clinical characteristics and treatment outcome

Importance: Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population. Objective: To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults. Design, Setting, and Participants: A nonrandomized, open-label clinical trial was conducted between August 2009 and August 2014 in Pittsburgh, Pennsylvania; St Louis, Missouri; and Toronto, Ontario, Canada, with older adults in a current major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnostic criteria. Data from biomarker analyses were reported according to the clinical trial archived plasma samples run in March 2021. Data were analyzed from June to November 2021. Exposure: Venlafaxine extended release (dose ranging from 37.5 mg to 300 mg daily) for up to 12 weeks. Main Outcomes and Measures: The association between a composite biomarker-based index (SASP index) and treatment remission in older adults with major depression was measured using clinical data and blood samples. Results: There were 416 participants with a mean (SD) age of 60.02 (7.13) years; 64% (265 participants) were self-reported female, and the mean (SD) Montgomery-Asberg Depression Rating Scale score was 26.6 (5.7). Higher SASP index scores were independently associated with higher rates of nonremission, with an increase of 1 unit in the SASP index score increasing the odds of nonremission by 19% (adjusted odds ratio, 1.19; 95% CI, 1.05-1.35; P = .006). In contrast, no individual SASP factors were associated with remission in LLD. Conclusions and Relevance: Using clinical data and blood samples from a nonrandomized clinical trial, the results of this study suggest that molecular and cellular senescence, as measured with the SASP index, is associated with worse treatment outcomes in LLD. Combining this index score reflecting interrelated biological processes with other molecular, clinical, and neuroimaging markers may be useful in evaluating antidepressant treatment outcomes. These findings inform a path forward for geroscience-guided interventions targeting senescence to improve remission rates in LLD. Trial Registration: ClinicalTrials.gov Identifier: NCT00892047

Diacutaneous fibrolysis versus passive stretching after articular immobilisation : muscle recovery and extracellular matrix remodelling

Introduction Atrophy and muscle shortening due to articular immobilisation are common problems in musculoskeletal rehabilitation. Muscle stretching mechanical stimuli might be considered as the golden standard procedure to improve muscle flexibility in rehabilitation. Muscle stretching generates mechanotransduction, potentiating specific gene expression and promotes sarcomerogenesis and extracellular matrix remodelling on shortened and atrophied muscles. Hypothesis Diacutaneous fibrolysis, like stretching, uses an external force to stress connective and muscle tissues mechanically to treat muscle shortening; thus, it is widely used in clinical practice even if there is no evidence to support it. Considering this subject, we have hypothesised that diacutaneous fibrolysis can generate mechanotransduction, affecting muscle hypertrophy and extracellular matrix remodelling after immobilisation. Evaluation of hypothesis We have designed a laboratory experimental study with a sample of 50 rats. The sample was randomly divided into five groups: Control group (n = 10) with non–immobilised rats; 3–week immobilisation group (n = 10); 3–week immobilisation/3–week non–immobilisation group (n = 10);3–week immobilisation/3–week stretching group (n = 10); and 3–week immobilisation/3–week diacutaneous fibrolysis group (n = 10). All rats had their left tibiotarsal joint immobilised in maximum plantar flexion with the orthotics for 3 consecutive weeks. After the immobilisation period, the intervention groups received their respective intervention on their left triceps suralis for 3 weeks. Dependent variables of the study were sarcomere analysis, polymerase chain reaction, connective tissue density, collagen birefringence and matrix metalloproteinases. Statistical analysis was performed using analysis of variance and Duncan post hoc test was applied for differences between groups. For all calculations, a 5% (p < 0.05) significance level was established. Conclusion If the hypothesis is confirmed, the present study might provide evidence to support the use of this physical therapy resource widely used to treat muscle dysfunctions

Towards an applied metaecology

The complexity of ecological systems is a major challenge for practitioners and decision-makers who work to avoid, mitigate and manage environmental change. Here, we illustrate how metaecology – the study of spatial interdependencies among ecological systems through fluxes of organisms, energy, and matter – can enhance understanding and improve managing environmental change at multiple spatial scales. We present several case studies illustrating how the framework has leveraged decision-making in conservation, restoration and risk management. Nevertheless, an explicit incorporation of metaecology is still uncommon in the applied ecology literature, and in action guidelines addressing environmental change. This is unfortunate because the many facets of environmental change can be framed as modifying spatial context, connectedness and dominant regulating processes - the defining features of metaecological systems. Narrowing the gap between theory and practice will require incorporating system-specific realism in otherwise predominantly conceptual studies, as well as deliberately studying scenarios of environmental change.We thank FAPESP (grants 2014/10470-7 to AM, 2013/04585-3 to DL, 2013/50424-1 to TS and 2015/18790-3to LS), CNPq (Productivity Fellowships 301656/2011-8 to JAFDF,308205/2014-6 to RP, 306183/2014-5 to PIP and 307689/2014-0 to VDP), the National Science Foundation (DEB 1645137 toJGH), the Natural Sciences and Engineering Council of Canada (SJL,PPN), and the Academy of Finland (grants 257686 and 292765 toMC) for support. This work contributes to the Labex OT-Med (no.ANR-11-LABX-0061), funded by the French government throughthe A*MIDEX project (no. ANR-11-IDEX-0001-02)

Association between perineal trauma and pain in primiparous women

Objective To identify the association between perineal trauma and pain in 473 primiparous women. Method Cross-sectional study in which pain was measured by the numerical pain scale (0 to 10 - 0 being no pain and 10 maximal pain). Results The prevalence and mean intensity of pain were 33.0% and 4.7 points (standard deviation = 2.0) in the numeric scale, respectively. Episiotomy represented the most frequent trauma (46.7%). The occurrence and intensity of the pain were associated with perineal trauma and postpartum time. Having perineal trauma tripled the chance of pain. Each hour elapsed following the birth reduced the chance of pain by 4.8%. Conclusion Primiparous women are subject to a high frequency of perineal trauma, with episiotomy being the most prominent. Perineal pain affects approximately one-third of primiparous women and is associated with the postpartum time and perineal traumas

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans

Development of microsatellite markers for identifying Brazilian Coffea arabica varieties

Microsatellite markers, also known as SSRs (Simple Sequence Repeats), have proved to be excellent tools for identifying variety and determining genetic relationships. A set of 127 SSR markers was used to analyze genetic similarity in twenty five Coffea arabica varieties. These were composed of nineteen commercially important Brazilians and six interspecific hybrids of Coffea arabica, Coffea canephora and Coffealiberica. The set used comprised 52 newly developed SSR markers derived from microsatellite enriched libraries, 56 designed on the basis of coffee SSR sequences available from public databases, 6 already published, and 13 universal chloroplast microsatellite markers. Only 22 were polymorphic, these detecting 2-7 alleles per marker, an average of 2.5. Based on the banding patterns generated by polymorphic SSR loci, the set of twenty-five coffee varieties were clustered into two main groups, one composed of only Brazilian varieties, and the other of interspecific hybrids, with a few Brazilians. Color mutants could not be separated. Clustering was in accordance with material genealogy thereby revealing high similarity