Performance Comparison of Bio-Inspired Algorithms for Optimizing an ANN-Based MPPT Forecast for PV Systems.

This study compares bio-inspired optimization algorithms for enhancing an ANN-based Maximum Power Point Tracking (MPPT) forecast system under partial shading conditions in photovoltaic systems. Four algorithms-grey wolf optimizer (GWO), particle swarm optimization (PSO), squirrel search algorithm (SSA), and cuckoo search (CS)-were evaluated, with the dataset augmented by perturbations to simulate shading. The standard ANN performed poorly, with 64 neurons in Layer 1 and 32 in Layer 2 (MSE of 159.9437, MAE of 8.0781). Among the optimized approaches, GWO, with 66 neurons in Layer 1 and 100 in Layer 2, achieved the best prediction accuracy (MSE of 11.9487, MAE of 2.4552) and was computationally efficient (execution time of 1198.99 s). PSO, using 98 neurons in Layer 1 and 100 in Layer 2, minimized MAE (2.1679) but had a slightly longer execution time (1417.80 s). SSA, with the same neuron count as GWO, also performed well (MSE 12.1500, MAE 2.7003) and was the fastest (987.45 s). CS, with 84 neurons in Layer 1 and 74 in Layer 2, was less reliable (MSE 33.7767, MAE 3.8547) and slower (1904.01 s). GWO proved to be the best overall, balancing accuracy and speed. Future real-world applications of this methodology include improving energy efficiency in solar farms under variable weather conditions and optimizing the performance of residential solar panels to reduce energy costs. Further optimization developments could address more complex and larger-scale datasets in real-time, such as integrating renewable energy sources into smart grid systems for better energy distribution.

Imported malaria cases by Plasmodium falciparum and Plasmodium vivax in Mexican territory: Potential impact of the migration crisis.

BACKGROUND: As the migratory flow to the USA has intensified in recent months, health problems associated have been identified. The aim of this work was the identification of malaria cases imported into Mexican territory. METHODS: Operational definitions of suspected and confirmed cases were used for investigation of malaria cases. Detection of parasitic entities by thick blood smear and molecular biology served as a confirmatory test. With the characteristics of the cases, a heat map was made to determine common clinical pictures. Finally, epidemiological analysis of cases was performed for the construction of timelines of imported malaria and the tracing of migratory routes. RESULTS: Twelve migrants from four countries were treated for presenting clinical symptoms with suspected dengue or malaria. Malaria was confirmed and two Plasmodium species were identified. From the epidemiological dates of arrival in Mexico, onset of symptoms and migratory routes, we speculate that ten cases acquired P. vivax during their crossing through Honduras, El Salvador or Guatemala. For the Guinea cases, we conclude that there was African importation of P. falciparum. CONCLUSION: The epidemiological panorama of malaria cases imported into Mexico show the need to join efforts to ensure universal access to health services, with the objective of timely detection of imported cases.

Wolbachia strengthens the match between pre-mating and early post-mating isolation in spider mites.

Endosymbiotic reproductive manipulators are widely studied as sources of post-zygotic isolation in arthropods, but their effect on pre-zygotic isolation between genetically differentiated populations has garnered less attention. We tested this using two partially isolated populations of the red and green colour forms of Tetranychus urticae, either uninfected or infected with different Wolbachia strains, one inducing cytoplasmic incompatibility and the other not. We first investigated male and female preferences, and found that, in absence of infection, females were not choosy, but all males preferred red-form females. Wolbachia effects were more subtle, with only the CI-inducing strain slightly strengthening colour-form based preferences. We then performed a double-mating experiment to test how incompatible matings affect subsequent mating behaviour and offspring production, as compared to compatible matings. Females mated with an incompatible male (infected and/or heterotypic) were more attractive and/or receptive to subsequent (compatible) matings, although analyses of offspring production revealed no clear benefit for this re-mating behaviour (i.e., apparently unaltered first male sperm precedence). Finally, by computing the relative contributions of each reproductive barrier to total isolation, we showed that pre-mating isolation matches both host-associated and Wolbachia-induced post-mating isolation, suggesting that Wolbachia could contribute to reproductive isolation in this system.

Morphometric measures and desaturations: Proposal for an index with improved accuracy for obstructive sleep apnea screening.

STUDY OBJECTIVE: To evaluate the sensitivity and specificity of the combined Kushida morphometric model (KMM) and the oxygen desaturation index (ODI) for screening individuals with obstructive sleep apnea. METHODS: Diagnostic test study with adults >18 years, both sexes, polysomnography, body mass index, neck circumference and intraoral measurements. RESULTS: 144 patients were invited; of these, 75 met the exclusion criteria. 55 individuals presented AHI ≥5 ev/h and 14, an AHI <5 ev/h. Three AHI cut-off points were evaluated: AHI ≥5, ≥15, ≥30 ev/h. When adopting the cut-off point of AHI ≥5 ev/h, the KMM showed sensitivity (SE) = 60.0 %, specificity (SP) = 71.4 % and 95 % confidence interval of the area under the curve (95 % CI of AUC) = 0.655; the combination of KMM and ODI (KMM + ODI) revealed SE = 73.0 %, SP = 71.4 % (95 % CI of AUC = 0.779) and the ODI showed SE = 76.4 % and SP = 92.9 % (95 % CI of AUC = 0.815). At the cut-off point of AHI ≥15 ev/h, the KMM presented SE = 64.1 %, SP = 76.7 % (95 % CI of AUC = 0.735); the KMM + ODI showed SE = 82.1 %, SP = 83.3 % (95 % CI of AUC = 0.895); and the ODI presented SE = 76.9 %, SP = 100.0 % (95 % CI of AUC = 0.903). For the cut-off point of AHI ≥30 ev/h, the KMM showed SE = 56.0 %, SP = 77.2 % (95 % CI of AUC = 0.722); the KMM + ODI revealed SE = 92.0 %, SP = 79.5 % (95 % CI of AUC = 0.926); and the ODI showed SE = 92.0 %, SP = 90.9 % (95 % CI of AUC = 0.941). CONCLUSION: The combination of oxygen desaturation index and Kushida morphometric model improved the sensitivity and specificity of this model regardless of obstructive sleep apnea severity suggesting greater effectiveness in risk prediction.

Mutational spectrum of breast cancer by shallow whole-genome sequencing of cfDNA and tumor gene panel analysis.

Breast cancer (BC) has different molecular subgroups related to different risks and treatments. Tumor biopsies for BC detection are invasive and may not reflect tumor heterogeneity. Liquid biopsies have become relevant because they might overcome these limitations. We rationalize that liquid cfDNA biopsies through shallow whole genome sequencing (sWGS) could improve the detection of tumor alterations, complementing the genomic profiling. We evaluated the feasibility to detect somatic copy number alterations (SCNAs) in BC using shallow whole genome sequencing (sWGS) in cfDNA from archived samples from National Cancer Institute of Colombia patients. We sequenced tumor tissues from 38 BC patients with different molecular subtypes using a gene panel of 176 genes significantly mutated in cancer, and by liquid biopsies using sWGS on 20 paired samples to detect SCNAs and compare with the tumor samples. We identified an extensive intertumoral heterogeneity between the molecular subtypes of BC, with a mean tumor load of 602 mutations in the gene panel of tumor tissues. There was a 12.3% of concordance in deletions in the cfDNA-tumor pairs considering only the genes covered by the panel encompassing seven genes: BRCA1, CDK12, NF1, MAP2K4, NCOR1, TP53, and KEAP1 in three patients. This study shows the feasibility to complement the genomic analysis of tumor tissue biopsies to detect SCNA in BC using sWGS in cfDNA, providing a wider identification of potential therapeutic targets.

Elevated level of extracellular vimentin is associated with an increased fibrin formation potential in sepsis: ex vivo swine study.

BACKGROUND: Sepsis can lead to coagulopathy and microvascular thrombosis. Prior studies, including ours, reported an increased level of extracellular vimentin in blood derived from septic patients. Moreover, we identified the contribution of extracellular vimentin to fibrin formation and to the fibrin clot structure ex vivo in plasma from septic patients. Here, we tested the status of plasma vimentin and its impact on fibrin clots using our recently described swine model of methicillin-resistant Staphylococcus aureus (MRSA) sepsis-induced coagulopathy. RESULTS: We employed ELISA, size-exclusion chromatography, vimentin antibodies, confocal microscopy, and turbidity assays on piglet plasma obtained at pre- and post-MRSA inoculation. Plasma vimentin level at 70 h post-MRSA inoculation was on average twofold higher compared to pre-infection (0 h) level in the same animal. Anti-vimentin antibody effectively reduced fibrin formation ex vivo and increased porosity in the fibrin clot structure generated from septic piglet plasma. In contrast to plasma at 0 h, the size-exclusion chromatography revealed that phosphorylated vimentin was in-complex with fibrinogen in septic piglet plasma. CONCLUSIONS: Thus, our swine model of sepsis-induced coagulopathy, reproduced increased extracellular circulating vimentin and subsequent potentiation of fibrin formation, often observed in septic patient. These outcomes validate the use of large animal models to investigate the dysregulated host immune response to infection leading to coagulopathy, and to develop new therapies for sepsis-induced disseminated microvascular thrombosis.

Dietary Zinc Intake and the Association of Insulin Level and HOMA-IR with Telomere Shortening in Mexican Children.

PURPOSE: The relationship between dietary zinc (Zn) intake, metabolic diseases, and telomere length has been little explored in the children population. This observational cross-sectional study assesses the association between obesity (OB), cardiometabolic traits, telomere length, and dietary Zn intake in children with normal weight (NW) and OB from Mexico City. METHODS: Anthropometric data, blood pressure, biochemical measurements, the homeostatic model assessment of insulin resistance (HOMA-IR) and leucocyte telomere length (determined by quantitative-PCR) were analyzed in 171 children with NW and 172 with OB. Furthermore, dietary Zn intake was evaluated in 117 children NW and 120 with OB. RESULTS: Telomere shortening was associated with fasting plasma insulin (FPI) and HOMA-IR in NW (beta coefficient [ß]FPI = -0.022 ± 0.008, p = 0.009; ßHOMA-IR = -0.096 ± 0.040, p = 0.020) and OB (ßFPI = -0.007 ± 0.002, p = 0.003; ßHOMA-IR = -0.034 ± 0.012, p = 0.005) children. Dietary Zn intake resulted negatively associated with FPI (ß = -2.418 ± 0.764, p = 0.002) and HOMA-IR (ß = -0.399 ± 0.014, p = 0.009) in children with OB. Then, in children with OB, the association between FPI, HOMA-IR, and telomere shortening was evaluated separately in groups of low, medium, and high dietary Zn intake (according to tertiles). The association between FPI, HOMA-IR, and telomere shortening was not significant in the high Zn intake group (PFPI = 0.633; PHOMA-IR = 0.567). CONCLUSION: Our results suggest that a high Zn intake may ameliorate the telomere shortening related to high FPI and HOMA-IR.

Citrulline and ADI-PEG20 reduce inflammation in a juvenile porcine model of acute endotoxemia.

Background: Arginine is a conditionally essential amino acid that is depleted in critically ill or surgical patients. In pediatric and adult patients, sepsis results in an arginine-deficient state, and the depletion of plasma arginine is associated with greater mortality. However, direct supplementation of arginine can result in the excessive production of nitric oxide (NO), which can contribute to the hypotension and macrovascular hypo-reactivity observed in septic shock. Pegylated arginine deiminase (ADI-PEG20, pegargiminase) reduces plasma arginine and generates citrulline that can be transported intracellularly to generate local arginine and NO, without resulting in hypotension, while maintaining microvascular patency. The objective of this study was to assess the efficacy of ADI-PEG20 with and without supplemental intravenous citrulline in mitigating hypovolemic shock, maintaining tissue levels of arginine, and reducing systemic inflammation in an endotoxemic pediatric pig model. Methods: Twenty 3-week-old crossbred piglets were implanted with jugular and carotid catheters as well as telemetry devices in the femoral artery to measure blood pressure, body temperature, heart rate, and respiration rate. The piglets were assigned to one of three treatments before undergoing a 5 h lipopolysaccharide (LPS) infusion protocol. Twenty-four hours before LPS infusion, control pigs (LPS; n=6) received saline, ADI-PEG20 pigs (n=7) received an injection of ADI-PEG20, and seven pigs (ADI-PEG20 + CIT pigs [n=7]) received ADI-PEG20 and 250 mg/kg citrulline intravenously. Pigs were monitored throughout LPS infusion and tissue was harvested at the end of the protocol. Results: Plasma arginine levels decreased and remained low in ADI-PEG20 + CIT and ADI-PEG20 pigs compared with LPS pigs but tissue arginine levels in the liver and kidney were similar across all treatments. Mean arterial pressure in all groups decreased from 90 mmHg to 60 mmHg within 1 h of LPS infusion but there were no significant differences between treatment groups. ADI-PEG20 and ADI-PEG20 + CIT pigs had less CD45+ infiltrate in the liver and lung and lower levels of pro-inflammatory cytokines in the plasma. Conclusion: ADI-PEG20 and citrulline supplementation failed to ameliorate the hypotension associated with acute endotoxic sepsis in pigs but reduced systemic and local inflammation in the lung and liver.

Setting Ranges in Potential Biomarkers for Type 2 Diabetes Mellitus Patients Early Detection By Sex-An Approach with Machine Learning Algorithms.

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic diseases in the world and poses a significant public health challenge. Early detection and management of this metabolic disorder is crucial to prevent complications and improve outcomes. This paper aims to find core differences in male and female markers to detect T2DM by their clinic and anthropometric features, seeking out ranges in potential biomarkers identified to provide useful information as a pre-diagnostic tool whie excluding glucose-related biomarkers using machine learning (ML) models. We used a dataset containing clinical and anthropometric variables from patients diagnosed with T2DM and patients without TD2M as control. We applied feature selection with three different techniques to identify relevant biomarker models: an improved recursive feature elimination (RFE) evaluating each set from all the features to one feature with the Akaike information criterion (AIC) to find optimal outputs; Least Absolute Shrinkage and Selection Operator (LASSO) with glmnet; and Genetic Algorithms (GA) with GALGO and forward selection (FS) applied to GALGO output. We then used these for comparison with the AIC to measure the performance of each technique and collect the optimal set of global features. Then, an implementation and comparison of five different ML models was carried out to identify the most accurate and interpretable one, considering the following models: logistic regression (LR), artificial neural network (ANN), support vector machine (SVM), k-nearest neighbors (KNN), and nearest centroid (Nearcent). The models were then combined in an ensemble to provide a more robust approximation. The results showed that potential biomarkers such as systolic blood pressure (SBP) and triglycerides are together significantly associated with T2DM. This approach also identified triglycerides, cholesterol, and diastolic blood pressure as biomarkers with differences between male and female actors that have not been previously reported in the literature. The most accurate ML model was selection with RFE and random forest (RF) as the estimator improved with the AIC, which achieved an accuracy of 0.8820. In conclusion, this study demonstrates the potential of ML models in identifying potential biomarkers for early detection of T2DM, excluding glucose-related biomarkers as well as differences between male and female anthropometric and clinic profiles. These findings may help to improve early detection and management of the T2DM by accounting for differences between male and female subjects in terms of anthropometric and clinic profiles, potentially reducing healthcare costs and improving personalized patient attention. Further research is needed to validate these potential biomarkers ranges in other populations and clinical settings.

The enigma of sleep: Implications of sleep neuroscience for the dental clinician and patient.

BACKGROUND: Sleep disturbances have been shown to result in considerable morbidity and mortality. It is important for dental clinicians to understand the neuroscience behind sleep disorders. TYPES OF STUDIES REVIEWED: The authors conducted a search of the literature published from January 1990 through March 2024 of sleep medicine-related articles, with a focus on neuroscience. The authors prioritized articles about the science of sleep as related to dental medicine. RESULTS: The authors found a proliferation of articles related to sleep neuroscience along with its implications in dental medicine. The authors also found that the intricate neuroscientific principles of sleep medicine are being investigated robustly. The salient features of, and the differences between, central and obstructive sleep apneas have been elucidated. Sleep genes, such as CRY, PER1, PER2, and CLOCK, and their relationship to cancer and neurodegeneration are also additions to this rapidly developing science. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The dental clinician has the potential to be the first to screen patients for possible sleep disorders and make prompt referrals to the appropriate medical professionals. This can be lifesaving as well as minimize potential future morbidity for the patient.

The impact of von Willebrand factor on fibrin formation and structure unveiled with type 3 von Willebrand disease plasma.

Normally, von Willebrand factor (VWF) remains inactive unless its A1A2 domains undergo a shear stress-triggered conformational change. We demonstrated the capacity of a recombinant A2 domain of VWF to bind and to affect fibrin formation, altering the fibrin clot structure. The data indicated that VWF contains an additional binding site for fibrin in the A2 domain that plays a role in the incorporation of VWF to the polymerizing fibrin. This study is to examine the hypothesis that active plasma VWF directly influence fibrin polymerization and the structure of fibrin clots. The study used healthy and type 3 von Willebrand disease (VWD) plasma, purified plasma VWF, fibrin polymerization assays, confocal microscopy and scanning electron microscopy. The exposed A2 domain in active VWF harbors additional binding sites for fibrinogen, and significantly potentiates fibrin formation (P < 0.02). Antibody against the A2 domain of VWF significantly decreased the initial rate of change of fibrin formation (P < 0.002). Clot analyses revealed a significant difference in porosity between normal and type 3 VWD plasma (P < 0.008), further supported by scanning electron microscopy, which demonstrated thicker fibrin fibers in the presence of plasma VWF (P < 0.0003). Confocal immunofluorescence microscopy showed punctate VWF staining along fibrin fibrils, providing visual evidence of the integration of plasma VWF into the fibrin matrix. The study with type 3 VWD plasma supports the hypothesis that plasma VWF directly influences fibrin polymerization and clot structure. In addition, a conformational change in the A1A2 domains exposes a hidden fibrin(ogen) binding site, indicating that plasma VWF determines the fibrin clot structure.

The effect of ADAMTS13 on graft-versus-host disease.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo-HSCT is associated with significant complications. The most common and debilitating among them is graft-versus-host disease (GVHD). In GVHD, donor-derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD-targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non-lymphoid tissues. In this study, we showed that Von Willebrand factor (VWF), an adhesion molecule secreted by activated endothelial cells, plays an important role in mouse models of GVHD. We investigated the effect of the VWF-cleaving protease ADAMTS13 on GVHD. We found that ADAMTS13 reduced the severity of GVHD after bone marrow transplantation from C57BL6 donor to BALB/C recipient mice. A recombinant VWF-A2 domain peptide also reduced GVHD in mice. We showed that ADAMTS13 and recombinant VWF-A2 reduced the binding of T cells to endothelial cells and VWF in vitro, and reduced the number of T cells in lymph nodes, Peyer's patches and GVHD-targeted organs in vivo. We identified LFA-1 (αLß2) as the binding site of VWF on T cells. Our results showed that blocking T-cell homing by ADAMTS13 or VWF-A2 peptide reduced the severity of the GVHD after allo-HSCT, a potentially novel method for treating and preventing GVHD.

Plasma Photoinactivation of Bacterial Isolated from Blood Donors Skin: Potential of Security Barrier in Transfusional Therapy.

The presence of skin bacteria capable of forming biofilm, exhibiting antibiotic resistance, and displaying virulence represents a significant challenge in the field of transfusion medicine. This underscores the necessity of enhancing the microbiological safety of blood and blood components against pathogens with virulent characteristics. The aim of this work was to demonstrate bacterial inactivation in plasma by using a photoinactivation method against virulent bacteria and to evaluate coagulation factors before and after treatment. Logarithmic loads of biofilm-producing, antibiotic-resistant, and virulent bacteria isolated from skin (Enterobacter cloacae, Klebsiella ozaenae, and Staphylococcus epidermidis) were used in artificial contamination assays of fresh frozen plasma bags and subjected to photoreduction. FVIII and FI activity were evaluated before and after photoinactivation. The photoinactivation of plasma was demonstrated to be an effective method for the elimination of these bacteria. However, the efficiency of this method was found to be dependent on the bacterial load and the type of test microorganism. Conversely, decay of coagulation factors was observed with net residual activities of 61 and 69% for FVIII and FI, respectively. The photoinactivation system could have a bias in its effectiveness that is dependent on the test pathogen. These findings highlight the importance of employing technologies that increase the safety of the recipient of blood and/or blood components, especially against virulent bacteria, and show the relevance of the role of photoinactivation systems as an option in transfusion practice.

Sleep Bruxism and Sleep Structure in Comorbid Insomnia and Obstructive Sleep Apnea (COMISA) Syndrome: A Polysomnographic Study.

Introduction: Comorbid insomnia and obstructive sleep apnea (COMISA) is not a well-identified sleep disorder, despite having a significant impact on health. This study investigates the relationship between sleep bruxism (SB) and sleep architecture in patients with COMISA, obstructive sleep apnea (OSA), and in those without any sleep disorders. Methods: 119 patients were included in the study and divided into three groups: OSA, COMISA, and a control group. Polysomnographic (PSG) examination provided parameters related to sleep architecture, OSA, and characteristics of SB. Results: The bruxism episode index (BEI) and other SB parameters were not found to be statistically different between the three groups (p > 0.05). There was no statistical difference in measured sleep architecture between the COMISA and OSA groups (p > 0.05). In comparison to the control group, participants in the COMISA group were found to have an increased apnea-hypopnea index (AHI), oxygen desaturation index (ODI), respiratory disturbance index (RDI), all arousals (AA), and respiratory arousals (RA) (p < 0.05). Among COMISA patients, AA and RA were shown to have a positive linear correlation with the number of bradycardia events per hour (r = 0.49, r = 0.48, p < 0.05). Conclusions: SB does not occur in patients with COMISA more frequently than in patients with OSA or those without any sleep disorders. PSG parameters are not specific for COMISA; therefore, in order to differentiate this disorder from OSA alone, a comprehensive patient assessment has to be performed.

Ethanol drinking at adulthood is sensitive to S1-R antagonism and is promoted by binge ethanol self-administration at adolescence.

BACKGROUND: Binge drinking at adolescence is a risk factor for problematic alcohol (ethanol) consumption later in life, yet the murine studies that modelled this phenomenon via ethanol self-administration have provided mixed findings. Antagonism of the sigma-1 receptor (S1-R) system at adolescence modulates ethanol's motivational effects and intake. It is still unknown, however, whether this antagonism would protect against enhanced ethanol intake at adulthood after adolescent binge ethanol exposure. METHODS: Exp. 1 and 2 tested adults male or female Wistar rats -exposed or not to ethanol self-administration at adolescence (postnatal days 31-49; nine 2-hour sessions of access to 8-10% ethanol)- for ethanol intake using 24-h two-bottle choice test (Exp. 1) or time restricted, single-bottle, tests (Exp. 2). Experiments 2-5 evaluated, in adolescent or adult rats, the effects of the S1-R antagonist S1RA on ethanol intake and on ethanol-induced conditioned taste or place aversion. Ancillary tests (e.g., novel object recognition, ethanol-induced locomotor activity) were also conducted. RESULTS: Adolescent ethanol exposure promoted ethanol consumption at both the restricted, single-bottle, and at the two-bottle choice tests conducted at adulthood. S1RA administration reduced ethanol intake at adulthood and facilitated the development of ethanol-induced taste (but not place) aversion. CONCLUSIONS: S1RA holds promise for lessening ethanol intake after chronic and substantial ethanol exposure in adolescence that results in heightened ethanol exposure at adulthood. This putative protective effect of S1-R antagonism may relate to S1RA exacerbating the aversive effects of this drug.

Comorbid Insomnia and Sleep Apnea: COMISA.

The term "comorbid insomnia and sleep apnea" (COMISA) has been used to categorize the co-occurrence of the most prevalent and impacting sleep disorders. Meanwhile, both insomnia and sleep apnea have been shown to be associated with increased stress levels and cardiometabolic risk, a major cause of mortality. The better knowledge about such convergence would be critical for better understanding pathophysiological pathways and mechanisms. This article provides an overview of epidemiologic aspects, clinical findings, and mechanisms subsiding COMISA. Odontostomatological approach with mandibular advancement devices are discussed as an effective therapeutic approach in these patients.

Enhancing Sleep Quality in Pediatric Intensive Care: A Chronobiological Perspective.

Biologic synchronized rhythmicity is a critical physiologic process. The lack of synchronized rhythms, mainly those showing a circadian basis, like sleep, heart rate, and arterial pressure, often leads to several organic challenges usually associated with adverse outcomes. Sleep itself, as an independent regulator of many crucial body functions, should preferentially occur with minimum interferences to optimize its plastic role toward structural and functional recovery and regeneration. Hence, patients will mostly benefit from both circadian and sleep-related optimized functions in order to improve prognosis and reduce patients' discharge times.

Phenotyping OSA: Conceptualization and Implications for Treatment with Mandibular Advancement Devices.

Obstructive Sleep Apnea (OSA) is a common medical disorder and the most impacting sleep disturbance. OSA derive from the narrowing of the upper airway during sleep, which result in recurrent episodes of ventilatory disturbances expressed by an increased airflow resistance (flow limitation and hypopneas) and often an absence of ventilation (apneas). The high heterogeneity in the clinical picture of OSA turns diagnostic and treatment challenging. In the last decade different phenotypes, referring to specific categories of patients that can be distinguished from others by features and related clinical meaningful attributes, were identified. Those phenotypes may predict clinically important outcomes as those deriving from MAD therapy.

Methylation marks in blood DNA reveal breast cancer risk in patients fulfilling hereditary disease criteria.

Less than 15-20% of patients who meet the criteria for hereditary breast and ovarian cancer (HBOC) carry pathogenic coding genetic mutations, implying that other molecular mechanisms may contribute to the increased risk of this condition. DNA methylation in peripheral blood has been suggested as a potential epigenetic marker for the risk of breast cancer (BC). We aimed to discover methylation marks in peripheral blood associated with BC in 231 pre-treatment BC patients meeting HBOC criteria, testing negative for coding pathogenic variants, and 156 healthy controls, through methylation analysis by targeted bisulfite sequencing on 18 tumor suppressor gene promoters (330 CpG sites). We found i) hypermethylation in EPCAM (17 CpG sites; p = 0.017) and RAD51C (27 CpG sites; p = 0.048); ii) hypermethylation in 36 CpG-specific sites (FDR q < 0.05) in the BC patients; iii) four specific CpG sites were associated with a higher risk of BC (FDR q < 0.01, Bonferroni p < 0.001): cg89786999-FANCI (OR = 1.65; 95% CI:1.2-2.2), cg23652916-PALB2 (OR = 2.83; 95% CI:1.7-4.7), cg47630224-MSH2 (OR = 4.17; 95% CI:2.1-8.5), and cg47596828-EPCAM (OR = 1.84; 95% CI:1.5-2.3). Validation of cg47630224-MSH2 methylation in one Australian cohort showed an association with 3-fold increased BC risk (AUC: 0.929; 95% CI: 0.904-0.955). Our findings suggest that four DNA methylation CpG sites may be associated with a higher risk of BC, potentially serving as biomarkers in patients without detectable coding mutations.