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Major depressive disorder (MDD) is associated with inflammation and a high level of comorbidities. Atypical depression (AD) is a MDD subtype based on DSM criteria, that could have specific underlying biological mechanisms. AD is associated with elevated cardiovascular (CVD) comorbidities, higher risk of suicide attempts, hypersomnia, and anxiety disorder. In this study, we aim to investigate if AD and polysomnographic parameters could be associated with low-grade inflammation (LGI). LGI is defined by a range from 3 to 10 mg/L of C-reactive protein levels. We carried out a retrospective cohort study in which 765 individuals with MDD were split into two groups: with and without LGI. Our results exhibit differences between the groups for the polysomnographic parameters, with the LGI group showing parameters already associated with inflammation such as reduced rapid eye movement sleep and elevated hypoxemia markers (identified as CVD risk factor). We found that AD is associated with LGI (OR 1.48; p = 0.047) after adjustment. Likewise, we found an LGI prevalence in AD higher (34.8%) than in MDD without atypical features (26.8%). Overall, these results confirm the low-grade inflammation feature of AD and highlight polysomnographic parameters associated with LGI that could also act as risk factors in this context.

Abstract Background Total hip or knee arthroplasties (THA/TKA) show favorable long-term effects, yet the recovery process may take weeks to months. Physical therapy (PT) following discharge from hospital is an effective intervention to enhance this recovery process. To investigate the relation between recovery and postoperative PT usage, including the presence of comorbidities, 6 months after THA/TKA. Methods Multicenter, observational study in primary THA/TKA patients who completed preoperative and 6 months postoperative assessments. The assessments included questions on PT use (yes/no and duration; long term use defined as ≥ 12 weeks), comorbidities (musculoskeletal, non-musculoskeletal, sensory comorbidities and frequency of comorbidities). Recovery was assessed with the HOOS/KOOS on all 5 subdomains. Logistic regression with long term PT as outcome was performed adjusted for confounding including an interaction term (comorbidity*HOOS/KOOS-subdomain). Results In total, 1289 THA and 1333 TKA patients were included, of whom 95% received postoperative PT, 56% and 67% received postoperative PT ≥ 12 weeks respectively. In both THA and TKA group, less improvement on all HOOS/KOOS domain scores was associated with ≥ 12 weeks of postoperative PT (range Odds Ratios 0.97–0.99). In the THA group the impact of recovery was smaller in patient with comorbidities as non- musculoskeletal comorbidities modified all associations between recovery and postoperative PT duration (Odds Ratios range 1.01–1.05). Musculoskeletal comorbidities modified the associations between Function-in-Daily-Living-and Sport-and-recreation recovery and postoperative PT. Sensory comorbidities only had an effect on Sport-and-recreation recovery and postoperative PT. Also the frequency of comorbidities modified the relation between Function-in-Daily-Living, pain and symptoms recovery and postoperative PT. In the TKA group comorbidity did not modify the associations. Conclusion Worse recovery was associated with longer duration of postoperative PT suggesting that PT provision is in line with patients’ needs. The impact of physical recovery on the use of long-term postoperative PT was smaller in THA patients with comorbidities. Trial registration Registered in the Dutch Trial Registry on March 13, 2012. TRIAL ID NTR3348; registration number: P12.047. https://www.trialregister.nl/trial/3197 .

Abstract Given the limited data in the literature, the aim of this study was to investigate the association between type 2 diabetes and anhedonic subtype of major depression in hypertensive individuals. Demographic and polysomnographic data from 323 hypertensive individuals recruited from the database of the Erasme Hospital Sleep Laboratory were analysed. Only individuals with a diagnosis of type 2 diabetes according to the diagnostic criteria of the American Diabetes Association at admission were included in the “diabetes group”. Logistic regression analyses were used to study the association between type 2 diabetes and anhedonic subtype of major depression in hypertensive individuals. The rate of type 2 diabetes was 18.9% in our sample of hypertensive individuals. After adjusting for major confounding factors, multivariate logistic regression analyses demonstrated that unlike the non‐anhedonic subtype of major depression, only the anhedonic subtype of major depression was significantly associated with higher likelihood of having type 2 diabetes in hypertensive individuals. In this study, the authors demonstrated that the anhedonic subtype of major depression is significantly associated with type 2 diabetes in hypertensive individuals, which could potentially open up new perspectives for the development of therapeutic strategies complementary to conventional treatments for type 2 diabetes in this subpopulation at high risk of complications related to the co‐occurrence of this metabolic disorder.

Abstract Peptide nucleic acids (PNAs) are potential antisense therapies for genetic, acquired, and viral diseases. Efficiently selecting candidate PNA sequences for synthesis and evaluation from a genome containing hundreds to thousands of options can be challenging. To facilitate this process, this work leverages machine learning (ML) algorithms and automated synthesis technology to predict PNA synthesis efficiency and guide rational PNA sequence design. The training data is collected from individual fluorenylmethyloxycarbonyl (Fmoc) deprotection reactions performed on a fully automated PNA synthesizer. The optimized ML model allows for 93% prediction accuracy and 0.97 Pearson's r. The predicted synthesis scores are validated to be correlated with the experimental high‐performance liquid chromatography (HPLC) crude purities (correlation coefficient R2 = 0.95). Furthermore, a general applicability of ML is demonstrated through designing synthetically accessible antisense PNA sequences from 102 315 predicted candidates targeting exon 44 of the human dystrophin gene, SARS‐CoV‐2, HIV, as well as selected genes associated with cardiovascular diseases, type II diabetes, and various cancers. Collectively, ML provides an accurate prediction of PNA synthesis quality and serves as a useful computational tool for informing PNA sequence design.

The current study aimed to compare deictic relational responding and Theory of Mind (ToM) performances in 60 non-clinical young adults with a profile of high versus low social anhedonia in order to investigate a possible link between social anhedonia and ToM functioning. The results indicated that social anhedonic participants were less accurate than controls (matched on age, gender and general intellectual competencies) on ToM tasks (P less than 0.001) and on complex deictic relational responding (P=0.05). Accuracy on reversing deictic relations explains 52% of the variance of ToM performance (P=0.000). These findings support the RFT approach to ToM and suggest the critical role of social contact for the remediation of deficits. (Contains 2 figures and 6 footnotes.)

PMOs (phosphorodiamidate morpholino oligomers) have huge potential for antisense therapy but complex and slow synthesis limits application. Here, the authors report the development of automated flow synthesis methods which reduce nucleobase coupling times from hours to minutes removing human errors and allow for high-throughput production.

Given the limited data available in the literature, the aim of this study was to investigate the potential role played by the temporal dynamics of anhedonia (lifelong anhedonia and recent changes in anhedonia) in the occurrence of suicidal ideations in major depressed subjects. The clinical data of 285 major depressed subjects recruited from the database of the Erasme Hospital Sleep Laboratory were analyzed. A score on item nine of the Beck Depression Inventory (BDI-II) ≥1 and/or an identification during the systematic psychiatric assessment were used to determine the presence of suicidal ideations. The association between anhedonia complaints (lifelong anhedonia and recent change in anhedonia) and suicidal ideations in major depressed subjects was assessed by logistic regression analyzes. The prevalence of suicidal ideations was 39.3% in our sample of major depressed subjects. After adjusting for the main confounding factors, multivariate logistic regression analysis demonstrated that unlike lifelong anhedonia, only recent changes in anhedonia were a risk factor for suicidal ideations in major depressed subjects. Given this potential involvement of the recent change in anhedonia in the occurrence of suicidal ideations in major depressed subjects, it seems essential to better identify and adequately manage this specific form of anhedonia in order to open new perspectives for the prevention of suicide in this particular sub-population.

Due to the few studies available, this study aimed to investigate the 10-year risk for cardiovascular disease (CVD) associated with COMISA (co-morbid insomnia and sleep apnea) in hypertensive subjects. Clinical data of 1009 hypertensive subjects extracted from the Sleep Laboratory database were analyzed. Framingham Risk Score ≥ 10% was used as a cut-off to identify hypertensive subjects with high 10-year risk for CVD. The association between 10-year risk for CVD and COMISA was investigated using logistic regression analyses. 65.3% of hypertensive subjects from our sample presented a high 10-year risk for CVD. After controlling for major confounding factors, multivariate logistic regression analyses demonstrated that unlike its components present separately, COMISA was significantly associated with high 10-year risk for CVD in hypertensive subjects (OR 1.88, 95% CI 1.01–3.51). In this study, we have demonstrated that the negative synergy between obstructive sleep apnea syndrome and insomnia disorder seems to play a central role in the 10-year risk for CVD in hypertensive subjects, which seems to indicate that the establishment of a systematic research and an adapted treatment of COMISA could open new perspectives to promote a better cardiovascular outcome in this specific subgroup of patients.

Major depressive disorder (MDD) is associated with inflammation and a high level of comorbidities. Atypical depression (AD) is a MDD subtype based on DSM criteria, that could have specific underlying biological mechanisms. AD is associated with elevated cardiovascular (CVD) comorbidities, higher risk of suicide attempts, hypersomnia, and anxiety disorder. In this study, we aim to investigate if AD and polysomnographic parameters could be associated with low-grade inflammation (LGI). LGI is defined by a range from 3 to 10 mg/L of C-reactive protein levels. We carried out a retrospective cohort study in which 765 individuals with MDD were split into two groups: with and without LGI. Our results exhibit differences between the groups for the polysomnographic parameters, with the LGI group showing parameters already associated with inflammation such as reduced rapid eye movement sleep and elevated hypoxemia markers (identified as CVD risk factor). We found that AD is associated with LGI (OR 1.48; p = 0.047) after adjustment. Likewise, we found an LGI prevalence in AD higher (34.8%) than in MDD without atypical features (26.8%). Overall, these results confirm the low-grade inflammation feature of AD and highlight polysomnographic parameters associated with LGI that could also act as risk factors in this context. [ABSTRACT FROM AUTHOR]

Abstract Background Sleep plays an important role in vulnerability to mood disorders. However, despite the existence of sex differences in vulnerability to mood disorders, no study has yet investigated the sex effect on sleep network organization and its potential involvement in vulnerability to mood disorders. The aim of our study was to empirically investigate the sex effect on network organization during REM and slow-wave sleep using the effective connectivity measured by Granger causality. Methods Polysomnographic data from 44 healthy individuals (28 men and 16 women) recruited prospectively were analysed. To obtain the 19 × 19 connectivity matrix of all possible pairwise combinations of electrodes by Granger causality method from our EEG data, we used the Toolbox MVGC multivariate Granger causality. The computation of the network measures was realized by importing these connectivity matrices into EEGNET Toolbox. Results In men and women, all small-world coefficients obtained are compatible with a small-world network organization during REM and slow-wave sleep. However, compared to men, women present greater small-world coefficients during REM sleep as well as for all EEG bands during this sleep stage, which indicates the presence of a small-world network organization less marked during REM sleep as well as for all EEG bands during this sleep stage in women. In addition, in women, these small-world coefficients during REM sleep as well as for all EEG bands during this sleep stage are positively correlated with the presence of subclinical symptoms of depression. Conclusions Thus, the highlighting of these sex differences in network organization during REM sleep indicates the presence of differences in the global and local processing of information during sleep between women and men. In addition, this small-world network organization less marked during REM sleep appears to be a marker of vulnerability to mood disorders specific to women, which opens up new perspectives in understanding sex differences in the occurrence of mood disorders.

The complaints of excessive daytime sleepiness are very common among adolescents. In addition, in this particular subpopulation, the presence of excessive daytime sleepiness is associated with negative impact on school performances, interpersonal difficulties (school friends or family), extracurricular activities, health and driving. In adolescents with complaints of excessive daytime sleepiness, it is important to perform a complete clinical assessment including systematic clinical interview, physical examination, sleep diaries, use of specific questionnaires and possible confirmatory tests. In adolescents, the main causes of excessive daytime sleepiness are sleep deprivation, inadequate sleep hygiene, insomnia disorders, circadian rhythm disorders, chronic somatic pathologies, psychiatric disorders, movement disorders related to sleep, respiratory disorders related to sleep, parasomnias, hypersomnia disorders and use of drugs or medications. Given the multiple aetiologies of excessive daytime sleepiness in adolescents, the implementation of targeted therapeutic strategies is essential in order to allow optimal management of this symptom and better prevention of its negative consequences. The aim of this review is therefore to provide health care professionals caring for adolescents with excessive daytime sleepiness complaints the currently recommended therapeutic strategies for the main aetiologies of excessive daytime sleepiness in this particular subpopulation.

The rapid spread of COVID-19 has become a health emergency causing an urgent need for drug treatments to control the outbreak, especially in more vulnerable individuals. This is reinforced by the fact that prophylactic vaccines and neutralizing monoclonal antibodies may not be fully effective against emerging variants. Despite all efforts made by the scientific community, efficient therapeutic options currently remain scarce, either in the initial, as well as in the advanced forms of the disease. From retrospective observational studies and prospective clinical trials, selective serotonin reuptake inhibitors (SSRIs), and other antidepressants with functional inhibition of acid sphingomyelinase (FIASMAs), have emerged as potential treatments of COVID-19. This has led to some prematurely optimistic points of view, promoting a large prescription of fluvoxamine in patients with COVID-19, that we think should be reasonably tempered.