Sensitive and precise nucleic acid detection is critical for clinical diagnostics and biotechnological advancements. Diagnostic in infectious disease field is very unique from diagnosing any other disease, that is time is of the essence; in outbreaks people die even with each passing hour in some cases, if the correct diagnosis wasn't make; for example Zika in particularly is a very challenging virus to diagnose, because it's in very few numbers of copies in the infected person, so it need high sensitive diagnostic approach to spot it, In particular, the advanced tools SHERLOCKv2 and DETECTR, give almost an immediate detection of attomolar amounts of pathogenic nucleic acids with specificity similar to that of PCR but with slight technical settings and that will guide the correct intervention for the patient. SHERLOCKv2 and DETECTR technologies are game changers for our ability to identify infectious disease and rapid detection of tumor DNA or cancer-related viruses with ultra-sensitive tests that don’t require a lot of complicated processing to go through. In this paper, we will review cutting-edge infectious disease diagnosis by CRISPR-Cas systems.

This study investigated the neuroprotective effects of methyl 3,4-dihydroxybenzoate (MDHB) against t-butylhydroperoxide(TBHP) induced oxidative damage in SH-SY5Y (human neuroblastoma cells) and the underlying mechanisms. SH-SY5Y were cultured in DMEM+10% FBS for 24 hours and pretreated with different concentrations of MDHB or N-acetyl-L-cysteine (NAC) for 4 hours prior to the addition of 40 μM TBHP for 24 hours. Cell viability was analyzed using the methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) assays. An annexin V-FITC assay was used to detect cell apoptosis rate. The 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to determine intracellular ROS levels. The activities of antioxidative enzymes (GSH-Px and SOD) were measured using commercially available kits. The oxidative DNA damage marker 8-OHdG was detected using ELISA. Western blotting was used to determine the expression of Bcl-2, Bax, caspase 3, p-Akt and Akt proteins in treated SH-SY5Y cells. Our results showed that MDHB is an effective neuroprotective compound that can mitigate oxidative stress and inhibit apoptosis in SH-SY5Y cells

This study presents an in–depth analysis and strategic planning techniques for approaching a situation or achieving progress related to information technology services of Nueva Ecija University of Science and Technology, particularly the San Isidro Campus. As an educational organization and one in the region excellence providers in education, the University has so much vital information to manage and services to offer to provide the student's needs through the Management Information System department, application of IT services as a competing instrument to combat tedious tasks such as online admission, grade release, enrollment information, and online learning, university announcement, and possible students’ internship. The objective of this study is to determine the influence of information technology in day–to–day activities of the organization and strategy applied to streamline processes more conveniently. The researchers develop a conceptual model that would analyze the IT services' impact by identifying its strengths, weaknesses, opportunities, and threats and cleverly act on it using the TOWS Matrix in generating strategic decisions. The overall results were beneficial to the University and MIS as a basis for formulating competitive strategies and integrating it in an extended development plan.

SHANK3 encodes scaffold protein involved in postsynaptic receptor density in glutamatergic synapses, including those in the parvalbumin (PV)+inhibitory neurons – the key players in generation of sensory gamma oscillations, such as 40-Hz auditory steady-state response(ASSR). Here we describe a clinical and neurophysiological phenotype of a 15-years old girl (SH01) with microduplication of 16389 bp in 22q13.33, affecting the SHANK3 gene in comparison to typically developing children (n=32). EEG were recorded during the binaurally presentation of 40-Hz clicks’ trains lasting for 500 ms with inter-trial intervals 500-800 ms. SH01 was diagnosed with mild mental retardation and learning disabilities(F70.88) and had problems with reading and writing, as well as smaller vocabulary than TD peers. Her clinical phenotype generally resembled the phenotype of previously described patients with 22q13.33 microduplication. SH01 had mild autistic symptoms but below the threshold for ASD diagnosis. No seizures or MRI abnormalities were reported. While SH01 had relatively preserved auditory event-related potential(ERP) with slightly attenuated P1, her 40-Hz ASSR was totally absent significantly deviating from TD’s ASSR. Absence of 40-Hz ASSR in patient with microduplication, affected SHANK3 gene, indicates deficient temporal resolution of the auditory system, that might underlie language problems, and represent neurophysiological biomarker of SHANK3 abnormalities.

Age-related diseases (ARDs) are the leading cause of death worldwide, and contribute to 90% of mortality in developed countries. Interestingly, the mortality rates of individual ARDs increase exponentially with age. Processes described by the exponential growth function typically involve a branching chain reaction or, more generally, a positive feedback loop. Here I propose that each ARD is mediated by one or several positive feedback loops (vicious cycles). I then identify critical vicious cycles in five major ARDs: atherosclerosis, hypertension, diabetes, Alzheimer’s and Parkinson’s. I also propose that the progression of ARDs can be halted by selectively interrupting the vicious cycles and suggest the most promising targets. An evolutionary perspective is also offered.

Garment sector has crucial working field in Turkey.It has also very high risky occupational health conditions and safety.The objective of this study is to define level of job level, work-related stress’ symptoms, social support and coping mechanisms of garment workers and to determine any related factors.This study is descriptive and cross-sectional. The study population comprised garment workers in the 16-65 age range. The data was collected by Assessment Form, The Brief Stress Coping Profile and Brief Job Stress Questionnaire. The level of work-related stress was statistically higher among the workers who had chronic disease, low economic, education status and poor quality of sleep. Psychological and physical physiological reactions to stress were found higher among women workers and those with chronic disease.It also was seen that job stress scores had a meaningful relationship with “emotional expression involving others” (r =.20) and “Avoidance and suppression” coping profile (r =.16; p <.01).Psychological symptom scores were found to have a low level of meaningful relationship with “Seeking help for solution” (r =-.08), “changing point of view” (r=.13) and “emotional expression involving others” coping profiles (r=.21). Work-related stress causes many health and behavioral problems. Work related reasons and coping profiles have powerful effects on stress.

Sleep is still considered a mystery, despite intense scientific investigation. Here we present the first complete biological theory of sleep. The role of sleep is to restore the optimal homeostatic state, which is essential for tissue performance and health. Non-rapid eye movement sleep (NREMS) restores cortical and most other brain neurons, via relaxed global activity managed by thalamocortical circuits. The role of REM sleep is to restore acetylcholine (ACh) neurons, which support focused responses and hence cannot participate in global oscillations. Sleep enhances learning and memory via state restoration and ACh-affected paths. NREMS induces a lack of consciousness because global synchronous activity prevents focused responses, which are essential for consciousness. Dreams result from focused neural firing during sharp-wave ripples and REMS, and have a sense of reality because they involve the same neurons representing focused perceptual responses during wake. Anesthetics utilize a variety of mechanisms that prevent focused responses.

There is increasing evidence and recognition that Lyme borreliosis, and other associated tick-borne diseases (LB/TBD) cause mental symptoms. Data was drawn from databases, search engines and clinical experience to review current information on LB/TBD. LB/TBD infections cause immune and metabolic effects that result in a gradually developing spectrum of neuropsychiatric symptoms, usually presenting with significant comorbidity and may include developmental disorders, autism spectrum disorders, schizoaffective disorders, bipolar disorder, depression, anxiety disorders (panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, intrusive symptoms), eating disorders, decreased libido, sleep disorders, addiction, opioid addiction, cognitive impairments, dementia, seizure disorders, suicide, violence, anhedonia, depersonalization, dissociative episodes, derealization and other impairments. Screening assessment followed by a comprehensive psychiatric clinical exam relevant to patient’s complaints and findings with a thorough history, mental status exam, review of systems, neurological exam, physical exam, a knowledgeable interpretation of laboratory findings, pattern recognition and clinical judgment facilitate diagnosis. Psychotropics and antibiotics may help improve functioning and prevent further disease progression. Awareness of the association between LB/TBD and neuropsychiatric impairments and studies of their prevalence in neuropsychiatric conditions can improve understanding of the causes of mental illness and violence and result in more effective prevention, diagnosis and treatment.

We consider the financial planning problem of a retiree wishing to enter a retirement village at a future uncertain date. The date of entry is determined by the retiree's utility and bequest maximisation problem within the context of uncertain future health states. In addition, the retiree must choose optimal consumption, investment, bequest and purchase of insurance products prior to her full annuitisation on entry to the retirement village. A hyperbolic absolute risk-aversion (HARA) utility function is used to allow necessary consumption for basic living and medical costs. The retirement village will typically require an initial deposit upon entry. This threshold wealth requirement leads to exercising the replication of an American put option at the uncertain stopping time. From our numerical results, active insurance and annuity markets are shown to be a critical aspect in retirement planning.

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. Herein, we used real-time PCR, western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the Nrf2 function. Surprisingly, we demonstrated that with up-regulated ROS and MDA levels, the effect of oxidative stress was obvious under H2O2 treatment. Anti-oxidative molecules were changed after the H2O2 exposure, whereby the anti-oxidative signaling of Nrf2 was activated with the increase of its downstream effectors, HO-1, NQO1 and γ-GCS. Additionally, the apoptosis levels gradually increased with oxidative stress and changes in the caspase-9, caspase-3, Bax and c-Fos levels, but not with caspase-8 and down-regulated Bcl-2. The enhanced antioxidant effect could not resist the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, et al, but not that of caspase-8. By contrast, silencing the expression Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on anti-oxidative and anti-intrinsic apoptosis by the activation of anti-oxidative enzymes.

Background: The aim of this study was to investigate the risk of obstructive sleep apnea (OSA) among ankylosing spondylitis (AS) patients in a nationwide population. Methods: We conducted a nationwide cohort study between 2003 and 2013 using the Taiwan National Health Insurance Research Database. The AS cohort included 2210 patients who were newly diagnosed between 2003 and 2013. Randomly selected non-AS controls were matched at a 1:4 ratio based on age, sex and index date. The endpoint of OSA was occurrence or the end of 2013. Cumulative incidences, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated after adjusting for age, gender, comorbidities and co-medications. Multivariate analyses were performed using Cox proportional hazards model. Due to violation of the proportionality assumption, landmark analysis was conducted to explore the risk of OSA during specific follow-up periods. Results: The adjusted HR (aHR) of OSA for the AS group was 2.826 (95% C.I. = 1.727–4.625) compared to the control group. On landmark analysis, aHR was 7.919 (95% C.I. = 3.169–19.792) for AS group 0–24 months from index date, and decreased to 1.816 (95% C.I. = 0.944–3.494) at ≥ 24 months from index date. On subgroup analyses increased risks of OSA in AS group compared to the control group were found for both males and females (aHRs were 4.533 (95% C.I. = 1.441–14.262) and 2.672 (95% C.I. = 1.522–4.692) for females and males, respectively). On age stratified analysis, there was significant risk only for the 40–59 age group with aHR of 3.913 (95% C.I. = 1.890–8.102). Conclusions: A higher risk of developing OSA was found among newly diagnosed AS cohort during the 12-year follow-up period, especially within 2 years after AS index date and in the 40–59 age group.

IgE-mediated wheat allergy is a gluten-related disorder. Wheat is one of the five most common food allergens in children. However, the natural history of IgE-mediated wheat allergy has seldom been described in the research literature. This study presents the current state of knowledge about the IgE-mediated wheat allergy in children.

Cellular oxidation is responsive to external and internal stimulation and is generated via signal molecules in defense mechanisms through networks of cell proliferation, differentiation, intracellular detoxification, bacterial infection, and immune reactions. Oxidative stress is not necessarily harmful per se; it depends on the balance between oxidation and antioxidation cascades, which are induced according to stimuli and can maintain oxygen homeostasis. The reactive oxygen species (ROS) that are generated during influenza virus (IV) infection have critical effects on both the virus and host cells. In this review, we outline the link between viral infection and ROS production, using IV as an example. We introduce the current state of knowledge on the molecular relationship between cellular oxidation mediated by ROS production and various effects of IV infection. We also summarize the potential anti-IV agents that act by targeting oxidative stress.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

The coronavirus COVID-19 epidemic has wreaked havoc on inhabitants of earth killing thousands of humans from more than 150 countries. The epidemic has put a number of countries under complete lockdown and the deadly situation is still prevailing around the globe. Vaccines have been long known as the most effective means of preventing viral infections. However, the lack of vaccines against COVID-19 has further worsened the situation. In this time of health crisis, it is the duty of scientific research community to provide alternative, effective and affordable strategies to vaccinate human bodies against viral infections-COVID-19 based on focused experimental approaches. Growing evidence suggests that certain natural foods and lifestyle changes have potential to optimize immune functions against viral infections including improving defense function, resistance towards invading pathogens, while maintaining self-tolerance. Boosting immune system gives an edge in fending off viruses and staying healthy. This review presents the six smart steps to add to your to-do list which let the inner work of immunity take place against viral infections-COVID-19 by dissolving the powers of disease and illness. Many of these factors are associated in their functions to improve or properly maintain the immune function such as promoting anti-inflammatory functions, inhibiting pro-inflammatory mediators, modulating cell-mediated immunity, altering the antigen-presenting cellular functions as well as promoting communication between the innate and adaptive immune responses. Thus, a scientific illustration of boosting the immune system by proper sleep, moderate exercise, avoiding stress, utilizing vitamins enriched foods, intake of more water and use of fruits and vegetables will hopefully help the community to deal with the coronavirus by vaccinating the human systems naturally.

Background: Appendicular skeletal muscle (or lean) mass (ALM) estimated using dual-energy X-ray absorptiometry (DXA) is considered to be a preferred method for sarcopenia studies. However, DXA is expensive, has limited portability, and requires radiation exposure. Bioelectrical impedance analysis (BIA) is inexpensive, easy to use, and portable; thus BIA might be useful in sarcopenia investigations. However, a large variety of models have been commercially supplied by different companies, and for most consumer products, the equations estimating ALM are not disclosed. It is therefore difficult to use these equations for research purposes. In particular, the BIA equation is often age-dependent, which leads to fundamental difficulty in examining age-related ALM loss. The aims of the current study were as follows: (1) to develop and validate an equation to estimate ALM using multi-frequency BIA (MF-BIA) based on theoretical models, and (2) to establish sarcopenia cutoff values using the equation for the Japanese population. Methods: We measured height (Ht), weight, and ALM obtained using DXA and a standing-posture 8-electrode MF-BIA (5, 50, 250 kHz) in 756 Japanese individuals aged 18 to 86-years-old (222 men and 301 women as developing equation group and 97 men and 136 women as a cross validation group). The traditional impedance index (Ht²/Z₅₀) and impedance ratio of high and low frequency (Z₂₅₀/Z₅) of hand to foot values were calculated. Multiple regression analyses were conducted with ALM as dependent variable in men and women separately. Results: We created the following equations: ALM = (0.6947 × (Ht²/Z₅₀)) + (−55.24 × (Z₂₅₀/Z₅)) + (−10,940 × (1/Z₅₀)) + 51.33 for men, and ALM = (0.6144 × (Ht²/Z₅₀)) + (−36.61 × (Z₂₅₀/Z₅)) + (−9332 × (1/Z₅₀)) + 37.91 for women. Additionally, we conducted measurements in 1624 men and 1368 women aged 18 to 40 years to establish sarcopenia cutoff values in the Japanese population. The mean values minus 2 standard deviations of the skeletal muscle mass index (ALM/Ht²) in these participants were 6.8 and 5.7 kg/m² in men and women, respectively. Conclusion: The current study established and validated a theoretical and age-independent equation using MF-BIA to estimate ALM and provided reasonable sarcopenia cutoff values.

This study was designed to assess variation of possible phytochemical compounds in the ethanolic extracts of Gigantochloa scortechinii rhizome. Destructive sampling was done by using selective random sampling method on four consecutive rhizomes from healthy clumps and was conducted at two natural forests and one secondary forest (planted). Homogenized sample were extracted using solvent extraction (70% ethanol) method. Ethanolic extracts of G. scortechinii rhizome were qualitatively analyzed using GC/MS GC2010 Plus, Shimadzu to determine the composition of phytochemical compounds and identified using FFNSC 1.3, NIST11, PMW_tox2, and Wiley229 spectral library. A qualitative variation was observed with a total of 56 compounds were identified and differentiated between study site and rhizome age. Results revealed that G. scortechinii rhizome contains various phytochemical compounds with potential as a plant of phytopharmaceutical importance. This is the first finding on the spatial and age-related effects of phytochemical compounds in a consecutive rhizome and of G. scortechinii rhizome specifically.

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

Understanding the complex relationship between sleep and memory is a major challenge in neuroscience. Many studies on memory consolidation in humans suggest that sleep triggers offline memory processes, resulting in less forgetting of declarative memory and performance stabilization in non-declarative memory. However, issues related to non-optimal experimental designs, task characteristics and measurements, and inappropriate data analysis practices can significantly affect the interpretation of the effect of sleep on memory. In this article, we discuss these issues and suggest constructive solutions to address them. We believe that implementing these solutions in future sleep and memory research will significantly advance this field by improving the understanding of the specific role of sleep in memory consolidation.

Objective: To examine the associations between menstruation features and symptoms and hormone-immune-metabolic biomarkers. Methods: Forty-one women completed questionnaires assessing characteristic menstruation symptoms, duration of menstrual cycle and number of pads used/day and completed the Daily Record of Severity of Problems (DRSP) during the consecutive days of their menstrual cycle. Menses-related symptoms (MsRS) were computed from the sum of 10 pre- and post-menses symptoms and the menstruation blood and duration index (MBDI) was computed based on the daily number of pads and duration of menses. We assayed serum levels of various biomarkers at days 7, 14, 21, and 28 of the subjects’ menstrual cycle. Results: MBDI was significantly associated with a) MsRS including low abdominal cramps, and gastro-intestinal (GI) and pain symptoms (positively); b) plasma levels of haptoglobin (Hp), CCL5, insulin growth factor (IGF)-1, and plasminogen activator inhibitor (PAI)1 (all positively); and c) estradiol and paraoxonase (PON)1 arylesterase activity (both inversely). MsRS were significantly predicted by CCL5 and IGF-1 (both positively) and progesterone (inversely). Low-abdominal cramps, and gastro-intestinal and pain symptoms were associated with lower progesterone levels. The MBDI+MsRS score was significantly predicted by the cumulative effects of (in descending order of importance): Hp, IGF-1, PON1 arylesterase, estradiol and PAI. Conclusion: Menstruation-related features including estimated blood loss, duration of menses, cramps, pain and GI symptoms are associated with hormone-immune-metabolic biomarkers, which mechanistically may explain those features. Women with an increased MBDI+MsRS index ≥ 0.666 percentile may be considered to have menstruation-related distress, including dysmenorrhea symptoms.

The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. SES can influence global health trajectory for an individual or a community, depending if SES is low or high. Sleep is sensitive to environmental stimuli, as well as living conditions. Plenty of studies linked sleep complaints with mood disorders, allostatic load or circadian disruption; but very few or none investigated deeply what happened earlier to sleep depending of SES. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. Even if recent evidence suggested that few of SES indicators like occupational status are linked with sleep disturbances, the relation between SES and health in general with sleep as an outcome or a mediator is not well documented. This scoping review synthetized studies which investigated physiological and psychological mechanisms resulting from a low SES and linked them with sleep disturbances as consequences or as mediators. This review also explore a possible role played by sleep in the relation between socioeconomic status and health inequalities.

The Munich ChronoType Questionnaire (MCTQ) has now been available for more than 15 years; its original publication has been cited 1,240 times (Google Scholar, May 2019); its online version, which was available until July 2017, has produced almost 300,000 entries from all over the world (MCTQ database). The MCTQ has gone through several versions, has been translated into 13 languages and has been validated against other more objective measures of daily timing in several independent studies. Besides being used as a method to correlate circadian features of human biology with other factors – ranging from health issues to geographical factors – the MCTQ gave rise to quantifying old wisdoms, like “teenagers are late” and has produced new concepts, like social jetlag. Some like the MCTQ’s simplicity and some view it critically; it is time to have a self-critical view on the MCTQ, to address some misunderstandings and give some definitions about MCTQ-derived chronotype and the concept of social jetlag.

We take what we see, hear, smell and feel for the reality. However, as neuroscientists, we know that this reality, that is, our perceptual world, is in fact made up by the brain from the processing of the nerve impulses coming from receptors. Ancient Greeks used to think that this perceptual world, sometimes called our 3D movie (Chalmers), is emitted and has its own physical nature. Given how real the 3D movie looks to us, it is still difficult today to consider that all we would be dealing with would be patterns of brain activity The present study thus aimed at testing whether the perceptual world could have some physical existence in addition to that of the neural patterns responsible for it. To achieve that goal, we tried to see whether brains could be sensitive to the 3D movie of others. This, admittedly unusual, operational hypothesis was based on two assumptions. First, brains are sensitive to the 3D movie, as our experience includes reactions to our perceptual world. Second, the physicality at stake does not differ across individuals. We recorded the event-related brain potentials (ERPs) evoked by stimuli of the international affective picture system in pairs of closely-related participants. Most importantly, they could neither see the stimuli simultaneously presented to their partners nor their reactions to them. As in Bouten et al. (2015), around 400 ms after the onset of the stimuli, ERPs started being more positive in inconsistent conditions. Namely, when the two subjects of each pair were presented with the same stimulus whereas they were told it would be a different one and vice-versa (i.e., different-stimuli expected to be same). ERPs were less positive when the two subjects of a pair were presented with the same stimuli and were told they were the same and conversely (i.e., different-stimuli expected to be different). The same experiment was then run in pairs of strangers. No significant effect of consistency on ERPs was observed even though participants could, this time, see, in the very periphery of their visual field, the reactions of their partner to the stimuli. We thus use the results of both studies to support a new version of the emission theory of consciousness and to suggest that the sensitivity to the perceptual world of others may depend on their prior familiarity with it.

Disrupted biological function, manifesting through the hallmarks of aging, poses as one of the largest threats to healthspan and risk of disease development, such as metabolic disorders, cardiovascular ailments, and neurodegeneration. In recent years, numerous geroprotectors, senolytics, and other nutraceuticals have emerged as potential disruptors of aging and may be viable interventions in the immediate state of human longevity science. In this review, we focus on the decrease of nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds to restore youthful NAD+ levels. Furthermore, these geroprotectors may enhance the efficacy of NMN supplementation while concurrently providing their own numerous health benefits. By analyzing the prevention of NAD+ degradation through inhibition of CD38 or supporting protective downstream agents of SIRT1, we provide a potential framework of the CD38/NAD+/SIRT1 axis through which geroprotectors may enhance the efficacy of NMN supplementation and reduce the risk of age-related diseases, thereby potentiating healthspan in humans.

Background: Schizophrenia is a severe psychiatric disorder that has a large impact on patients’ lives. In addition to Western medicine, the use of additional treatments, such as acupuncture, in treating the positive, negative, and cognitive symptoms is increasing. Methods: We conducted a systematic review on the use of acupuncture as an add-on treatment for patients with schizophrenia that are in regular care, with a special focus on the treatment of the often accompanying co-morbid sleep disorders. In this study, we searched the Medline, ScienceDirect, Cochrane Library, Scopus, and ERIC databases with a cut-off date of December 31, 2017, thereby following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Results: Our search resulted in 26 eligible studies. Most studies showed limited evidence for the use of acupuncture as add-on therapy in the treatment of clinical symptoms, but beneficial effects have been reported in the treatment of co-morbid sleep disorders. Conclusions: Limited evidence was found for the use of acupuncture as add-on therapy in the treatment of patients with schizophrenia; however, positive results were found in the treatment of sleep disorders, but this result needs to be confirmed in large, randomized, controlled trials.

Objectives: To determine the effects of caffeine consumption on the sleep habits and lifestyle of medical students. Methods: A cross-sectional study was conducted at Jinnah Sindh Medical University (JSMU) and Hamdard College of Medicine. On 422 undergraduate students aged 18-25 years, through random sampling. The duration of the study was from January 2019 to June 2019. The data was collected through self-administered questionnaire which included data regarding sleep habits and lifestyle of medical students. Results: Majority (81.6%) of the students consumed caffeine while only (18.4%) did not. One third of the participants (31.8%) reported caffeine consumption increased their academic performance and (57.3%) reported that it does not. More than half of the participants (63.3%) who consumed caffeine slept during class, whereas (47.2%) never had difficulty in falling asleep during the night. Conclusion: This research concluded that caffeine does have some role on sleep habits of medical students as they tend to have less sleep hours, experience day time dysfunction, average quality of sleep, and falling asleep during class. It has been concluded that caffeine has no effect on eating habits of medical students however, it does increase the screening time, keeping them active.

The present study was conducted to evaluate the effects of dietary supplementation of tea polyphenol （TP） on serum hormone, serum enzyme activity, antioxidant-related and immune-related gene expression of laying hens under heat stress. A total of 288 Chinese yellow chicken (186 days old) were randomly distributed among two treatments, each of which included 6 replicates of 24 hens. Dietary treatments were that the basal diet was supplemented with 200 mg / kg tea polyphenol. The study lasted for 7 weeks, including 1 week of adaptation and 6 weeks of the formal test. The content of high-density lipoprotein cholesterol (HDL-C) and total protein (TP) in serum significantly decreased by dietary supplementation with tea polyphenol. Dietary tea polyphenol supplementation improved serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzyme activity and decreased serum malondialdehyde (MDA) content in treatments compared to the control. However, supplementation of tea polyphenol did not affect the activity of serum catalase (CAT). The results indicated that long-term feeding of tea polyphenols help to increase the amount of hormones (FSH, E2) associated with reproduction in laying hens and thus improve egg production. It also improved the immune function of laying hens in high temperature environments. Adding tea polyphenols to the diet can significantly increase the serum IgG, IgM content of the laying hens and can upregulate the IgA content. Dietary supplementation of tea polyphenols in the laying hens significantly increased the expression of antioxidant enzyme-related genes (SOD, CAT and GPX1) in the liver. Moreover, the addition of tea polyphenols significantly increased the expression of immune-related genes (Interferon-γ (INF-γ), Interleukin 2 (IL-2) and Interleukin 4 (IL-4)) in the spleen. It is concluded that addition of tea polyphenols has a positive effect on antioxidant activity and immune function of laying hens.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating condition, probably of multifactorial etiology. No effective approved drugs are currently available for its treatment. Several studies have proposed symptomatic treatment with melatonin and zinc supplementation in chronic illnesses; however, little is known about the synergistic effect of this treatment on fatigue-related symptoms in ME/CFS. The primary endpoint of the study was to assess the effect of oral melatonin plus zinc supplementation on fatigue in ME/CFS. Secondary measures included participants’ sleep disturbances, anxiety/depression, and health-related quality of life. A proof-of-concept, 16-week, randomized, placebo-controlled, double-blind trial was conducted in 50 ME/CFS patients assigned to receive either oral melatonin (1 mg) plus zinc (10 mg) supplementation (n = 24) or matching placebo (n = 26) once daily. Endpoint outcomes were evaluated at baseline and then reassessed at 8 and 16 weeks of treatment and 4 weeks after treatment cessation, using self-reported outcome measures. Treatment was safe and well-tolerated. The most relevant results were the significant reduction in the perception of physical fatigue in the active group at the final follow-up versus placebo (p < 0.05), and the significant improvement in the physical component summary at all follow-up visits in the experimental group. Our findings suggest that oral melatonin plus zinc supplementation for 16 weeks is safe and potentially effective in reducing fatigue and improving the quality of life in ME/CFS. This clinical study was registered on ClinicalTrials.gov (NCT03000777).

The fear of missing out (FoMO) is characterized in the literature as a fear that others are having rewarding experiences while one is missing out, and a constant need to keep connected with one’s social network. Driven by Social Determination Theory (SDT) FoMO has been linked with Problematic Social Networking Sites use (PSNSU), negative affectivity (NA), self-esteem (SE) and sleep disturbances. The present study reports findings from 512 individuals (79.1% women, mean age 30.5 years, SD= 8.61). Structural equation modelling (SEM) suggests that the duration of SNSs use and the numbers of SNSs platforms actively used partially mediated the relationship between FoMO and PSNSU. In turns, PSNSU partially mediated the relationship between FoMO and NA. Furthermore, the present study has extended the literature by incorporating the Vulnerability Model in the FoMO concept, identifying that SE partially mediated the relationship between FoMO and NA, while NA fully mediated the relationship between FoMO and sleeping disturbances. Accordingly, the present has extended previous research findings in showing exercise as a potential protective factor to prevent against FoMO. Practical and theoretical implications are discussed.

Here, we review findings and trends in sleep research in 2020-2021 demonstrating how COVID-19 and sleep disorders can induce the BBB leakage via neuroinflammation, which might contribute to the 'coronasomnia' phenomenon. The new studies suggest that the controlling of sleep hygiene and quality should be incorporated into the rehabilitation of COVID-19 patients. We also discuss perspective strategies for prevention of COVID-19-related BBB disorders. We demonstrate that sleep might be a novel biomarker of the BBB leakage and the analysis of sleep EEG patterns can be a breakthrough non-invasive technology for diagnosis of the COVID-19-caused BBB disruption.

Sleep disorders (SD) have a complex aetiology, and socioeconomic status (SES) as determined by social class, household income, ethnicity and education plays an important role in their development. As SD are associated with cognitive impairment and mood disorders, they in turn impact SES. Socioeconomic status also influences allostatic load caused by chronic accumulation of stress throughout life. Environmental and psychological stressors have a direct effect on SD, and they are modulated by SES, in combination with comorbidities like obesity and cardiovascular disease. This review explores the recent theories about the influence of SES on the development of SD in the general population, whether or not occurring with comorbidities, and also focusses on the interplay between socioeconomic status, circadian rhythms, aging and clinical outcomes like metabolic diseases and cancer.

Hospitalized patients frequently have disordered and poor-quality sleep due to a variety of both intrinsic and extrinsic factors. These include frequent nighttime intrusions, insomnia related to pain and unfamiliar environments, dark conditions during the day with loss of natural light, and disruption of natural sleep cycle due to illness. Sleep wake disturbances can result in deleterious consequence on physical, emotional and cognitive status, which may impact patient satisfaction, clinical recovery, and hospital length of stay. Despite this, clinicians frequently fail to document sleep disturbances and are generally unaware of best practices to improve sleep quality in the hospital. The purpose of this review is to discuss sleep disturbances in hospitalized patients with a focus on causes of sleep disturbance, effect of poor quality sleep, high risk populations, considerations for surveillance and prevention, as well as pharmacologic and non-pharmacologic options for treatment.

Today, due to recent developments in technology, children devote plenty of time for screen viewing. However, its harmful effects are not yet clear. The purpose of present study was to examine the associations among screen viewing and sleep duration, and body mass index (BMI) in under-five years old children. This cross-sectional study was conducted with 322 under-five healthy children that were selected using multistage stratified cluster sampling method in 2017. The data that were gathered by time-use diary method were analyzed using Kolmogorov-Smirnov test, Spearman correlation tests, multiple linear regression analysis, one-way ANCOVA, two-way ANCOVA. There was a negative correlation between screen time and sleep duration (rs = -0.42, p = 0.00), positive correlation between screen time and BMI (rs = 0.38, p = 0.00) and sleep duration negatively correlated with BMI (rs = -0.22, p = 0.00). screen viewing was a predictive factor for both sleep duration (β = -0.26, p = 0.00) and BMI (β = -0.26, p = 0.00). screen viewing had a significant impact on sleep duration (4, 314) = 5.02, P = 0.001) and BMI (F (4, 314) = 1.16, P=0.298). Results of this study indicated that screen viewing is related to sleep duration and BMI in under-five children. furthermore, screen time has an impact on sleep duration and BMI scores of children. findings of our study suggest that sleep duration negatively is associated with BMI in under-five-year-old children.

The importance of diet and the gut-brain axis for brain health and cognitive function is increasingly acknowledged. Dietary interventions are tested for their potential to prevent and/or treat brain disorders. Intermittent fasting (IF), the abstinence or strong limitation of calories for 12 to 48 hours, alternated with periods of regular food intake, has shown promising results on neurobiological health in animal models. In this review article, we discuss the potential benefits of IF on cognitive function and the possible effects on the prevention and progress of brain-related disorders in animals and humans. We do so by summarizing the effects of IF which - through metabolic, cellular and circadian mechanisms - lead to anatomical and functional changes in the brain. Our review shows that there is no clear evidence of a positive short-term effect of IF on cognition in healthy subjects. Clinical studies show benefits of IF for epilepsy, Alzheimer’s disease and multiple sclerosis on disease symptoms and progress. Findings from animal studies show mechanisms by which Parkinson’s disease, ischaemic stroke, autism spectrum disorder and mood- and anxiety disorders could benefit from IF. Future research should disentangle whether positive effects of IF hold true regardless of age or the presence of obesity. Also, variations in fasting patterns, total caloric intake and intake of specific nutrients may be relevant components of IF success. Longitudinal studies and Randomized Clinical Trials (RCTs) will provide a window into the long-term effects of IF on the development and progress of brain-related diseases.

Exercise facilitates weight control, partly through effects on appetite regulation. Single bouts of exercise induce a short-term energy deficit without stimulating compensatory effects on appetite, whilst limited evidence suggests that exercise training may modify subjective and homeostatic mediators of appetite in directions associated with enhanced meal-induced satiety. However, large variability in responses exists between individuals. This article reviews the evidence relating to how adiposity, sex and habitual physical activity modulate exercise-induced appetite, energy intake and appetite-related hormone responses. The balance of evidence suggests that adiposity and sex do not modify appetite or energy intake responses to acute or chronic exercise interventions, but individuals with higher habitual physical activity levels may better adjust energy intake in response to energy balance perturbations. The effect of these individual characteristics and behaviours on appetite-related hormone responses to exercise remains equivocal. These findings support the continued promotion of exercise as a strategy for inducing short-term energy deficits irrespective of adiposity and sex, as well as the ability of exercise to positively influence energy balance over the longer term. Future well-controlled studies are required to further ascertain potential mediators of appetite responses to exercise.

The workplace is an ideal setting for health promotion. The regular medical examination of workers enables us to screen for numerous diseases, spread good practices and correct lifestyles, and obtain a favourable risk/benefit ratio. The continuous monitoring of the level of workers' wellbeing using a holistic approach that goes beyond the simple prevention of occupational risks enables us to promptly identify problems in work organization and the company climate. Problems of this kind can be adequately managed by using a participatory approach. In this study participatory ergonomics groups were used to improve occupational life in a small company. After intervention we observed a reduction in levels of perceived occupational stress measured with the effort / reward imbalance model, and an improvement in psychological wellbeing assessed by means of the Goldberg anxiety / depression scale. Although the limited size of the sample calls for a cautious evaluation of this study, the GEP© strategy proved to be a useful tool due to its cost-effectiveness.

Chronic degeneration of the Retinal Pigment Epithelium (RPE) is a precursor to pathological changes in the outer retina. The RPE monolayer, which lies beneath the neuroretina, daily internalises and digests large volumes of spent photoreceptor outer segments. Impaired cargo handling and processing in the endocytic/phagosome and autophagy pathways leads to the accumulation of lipofuscin and N-retinylidene-N-retinylethanolamine aggregates and chemically-modified compounds such as malondialdehyde and 4-hydroxynonenal within RPE. These contribute to increased proteolytic and oxidative stress, resulting in irreversible damage to post-mitotic RPE cells and development of blinding conditions such as Age-related Macular Degeneration, Stargardt disease and Choroideremia. Here, we review how impaired cargo handling in the RPE results in their dysfunction, discuss new findings from our laboratory and consider how newly discovered roles for lysosomes and the autophagy pathway could provide insights into retinopathies. Studies of these dynamic, molecular events have also been spurred on by recent advances in optics and imaging technology. Mechanisms underpinning lysosomal impairment in other degenerative conditions including storage disorders, a-synuclein pathologies and Alzheimer’s disease are also discussed. Collectively, these findings help transcend conventional understanding of these intracellular compartments as simple waste disposal bags to bring about a paradigm shift in the way lysosomes are perceived.

Background: Antibiotic lock therapy is an interventional modality used for treatment and prevention of central-line associated bloodstream infections. Stability and compatibility data for combinations are lacking, limiting clinical use. Objective: Compatibility and stability of daptomycin lock solutions in combination with azithromycin, gentamicin, and heparin or sodium citrate were evaluated up to 96 hours. Methods: Eight candidate lock solutions were prepared for compatibility and stability testing. All solutions were prepared in glass vials, and included daptomycin 1mg/mL in varying combinations with heparin 100 – 1,000 units/mL, trisodium citrate, azithromycin and/or gentamicin. Lactated Ringer’s solution was added as a diluent in a sufficient quantity to bring the total volume up to 5mL. Drug stability in the admixture was determined by the degradation of the components. The quantification of drugs was performed using Waters Alliance HPLC using Phenomenex Luna C8 (2), 150*2.6mm, 5µ column. A gradient run was executed for 20 minutes with 0.45% ammonium dihydrogen phosphate, pH 3.25 as eluent A and acetonitrile as eluent B at a flow rate of 1.0mL/min. Each solution was visually inspected for particulates and color change. Lock solutions were tested in triplicate. Results: Daptomycin degradation was <10% for all solutions at 48 hours, and for 7 of the 8 solutions at 72 hours. Gentamicin degradation was <5% for solutions in combination with daptomycin and trisodium citrate. No physical incompatibilities were detected. Conclusion: Study data support the stability and compatibility of daptomycin with additives in solution, allowing for fewer exchanges and longer dwell times for a lock solution. The addition of azithromycin or gentamicin may offer synergy and/or extended spectrum of activity. Daptomycin bioactivity with trisodium citrate needs confirmation.

Three types of wakefulness appeared along the vertebrate’s phylogeny and ontogeny: spinal-rhombencephalic in fish, brainstem-diencephalic in reptiles and cortical in mammals, in which the paralyzed spinal-rhombencephalic wake and the brainstem-diencephalic wake remain as REMS and NREMS The spinal-rhombencephalic and cortical types of wake are inherently anti-homeostatic. Animals must forage, reproduce, and survive to predation disregarding the environmental circumstances, hence temporarily forgetting the homeostatic regulation. After fulfilling the vital functions, the brainstem-diencephalic wake recovers the homeostatic control. The phasic signs of REMS are adaptive in immature mammals, serving for demanding heat, milk and defense to their mother. These advantages outweigh the REMS' poikilostasis in infants. The adults’ poikilostasis of REMS is harmless in thermoneutral environments but is mal-adaptive in aquatic environments in which REMS is reduced or even disappears. These exceptions explain the anomalous examples of REMS. An on-off hypothalamic switch homeostatically regulates the entrance and exit from REMS. Furthermore, the vital phasic signs of REMS depend on a second pontine proportional homeostatic control. Altogether, they regulate the expression of REMS.

The link between language processing and motor systems has been the focus of increasing interest to Cognitive Neuroscience. Some classical papers studying Event Related Potentials (ERPs) induced by linguistic stimuli have found differences in electrophysiological activity when comparing action and non-action words; more specifically, a bigger p200 for action words. On the other hand, a series of studies have validated the use of a grip force sensor (GFS) to measure language-induced motor activity during both isolated words and sentence listening, finding that action words induce an augmentation in the grip force around 250-300 ms after the onset of the stimulus. The purpose of the present study is to combine both techniques to assess if the p200 is related to the augmentation of the grip force measured by a GFS. We measured ERP and GFS changes elicited by listening to action and non-action words while maintaining an active grasping task in 10 healthy subjects. Our results show that the amplitude of the p200 in central electrodes is correlated to the augmentation in the GFS around 300 ms induced by linguistic stimuli. To our knowledge, this is the first study where the electrophysiological activity and the changes in the grip force induced by auditory language processing are put together, opening new venues of interpretation for the sensorimotor interaction in language processing.

Choroidal neovascularization (CNV) is a key pathological feature of several of the leading causes of vision loss including neovascular age-related macular degeneration. Here we show that a calreticulin anti-angiogenic domain (CAD)-like peptide 27, CAD27, inhibited in vitro angiogenic activities, including tube formation and migration of endothelial cells, and suppressed vascular sprouting from rat aortic ring explants. In rat model of laser-induced CNV, we demonstrate that intravitreal injection of CAD27 significantly attenuated the formation of CNV lesions as measured via fundus fluorescein angiography and choroid flat-mounts (19.5% and 22.4% reductions at 10μg and 20μg of CAD27 injected, respectively). Similarly, the reduction of CNV lesions was observed in the groups of rats that had received topical applications of CAD27 (choroid flat-mounts: 17.9% and 32.5% reductions at 10μg/mL and 20μg/mL of CAD27 installed, respectively). Retinal function was unaffected, as measured using electroretinography in both groups received interareal injection or topical applications of CAD27 at least for 9 days. These findings show that CAD27 can be used as a potential therapeutic alternative for targeting CNV in the diseases such as neovascular age-related macular degeneration.

The Japanese Association for Acute Medicine Committee recently proposed a novel classification system for the severity of heat-related illnesses. The illnesses are simply classified into three stages based on symptoms and management or treatment. Stages I, II, and III broadly correspond to heat cramp and syncope, heat exhaustion, and heat stroke, respectively. Our objective was to examine whether this novel severity classification is useful in the diagnosis by healthcare professionals of patients with severe heat-related illness and organ failure. A nationwide surveillance study of heat-related illnesses was conducted between June 1 and September 30, 2012, at emergency departments in Japan. Among the 2130 patients who attended 102 emergency departments, the severity of their heat-related illness was recorded for 1799 patients, who were included in this study. In the patients with heat cramp and syncope or heat exhaustion (but not heat stroke), the blood test data (alanine aminotransferase, creatinine, blood urea nitrogen, and platelet counts) for those classified as stage III were significantly higher than those of patients classified as stage I or II. There were no deaths among the patients classified as stage I. This novel classification may avoid underestimating the severity of heat-related illness.

Maxillomandibular advancement (MMA) is a surgical intervention that reduces the symptoms of obstructive sleep apnea via anterior repositioning of the upper and lower jaws. Pre-operative orthodontic alignment is often a critical component in aiding MMA. Orthodontia are important in intraoperative anchorage for intermaxillary fixation, healthy post-operative occlusion, and post-operative skeletal stability. Sequential clear aligners (SCA) refer to removable orthodontic appliances that are replaced at regular intervals to stimulate dental migration without the use of bonded hardware. These aligners have demonstrated efficacy in aiding orthognathic surgery for dentofacial deformities, which share some technical similarities with MMA for OSA. Here, we explore the treatment protocol for MMA followed by post-operative SCA treatment. Our experiences show that post-operative orthodontic treatment with SCAs results in similarly successful post-operative surgical outcomes given that the patient’s pre-operative occlusion is stable.

Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14), which has implication on viral pathogenicity and infection. Here, we aimed to identify (in-silico) the similarities between different members of coronavirus family. The analysis included 50 coronavirus proteomes, including SARS-CoV-2 (COVID-19), to find the variation of the number of protein functional motifs and domain in each coronavirus. For this role, we used the experimentally validated domain (motif) that known to be crucial for viral infection. Although human CoVs are classified within one genus, we found variations among them. SARS-CoV-1, SARS-CoV-2 and MERS-CoV encode different type of domains, which has implications on the molecular interactions triggered by each virus within human cells. Secondly, we used functional motifs to reconstruct the potential molecular pathways or interactions triggered by SARS-CoV-2 proteins within human cell.

The objective of this review is to do an overview about the current knowledge of Anti Iglon5 Syndrome, a disease that was first described in 2014. The IgLON proteins are a family of cell adhesion molecules and the presence of antibodies against IgLON5 are crucial for diagnosis of Anti IgLON5 Syndrome. This syndrome has an expanded clinical spectrum that involves prominent sleep disorder, progressive bulbar dysfunction, gait instability with abnormal eye movements reminiscent and cognitive deterioration sometimes associated with chorea. The main neuropathological finding is the neuronal loss with hyperphosphorylated tau (p-Tau) protein accumulation at hypothalamus, brainstem tegmentum, hippocampus, periaqueductal gray matter, medulla oblongata and upper cervical cord. The exact pathogenesis is still unclear and involves a neurodegenerative process and autoimmune response. The early diagnosis is important to avoid unnecessary tests and prevent complications. Important resources for diagnosis are the antibody testing of serum and CSF for IgLON5-IgG. The mortality of anti IgLON5 syndrome is high and new studies published described a good response to immune therapy. However, the response to immune therapy depends of some clinical and analytical characteristic. In addition, future studies are needed to thoroughly study the aspects of pathogenesis and treatment of this important pathological syndrome.

Compressive sensing (CS) is a technique that allows a signal vector to be reconstructed with a number of linear measurements far fewer than its size. In this study, optical hybrid cryptography with simultaneous compressive sensing based on orthogonal matching pursuit (OMP) is proposed as an alternative solution to the two important problems in communications, namely, effective / efficient / signal processing and secure encryption/decrypton. The whole system is able to both compress and encrypt data with attack immunity.

The aim of this cross-sectional study was to assess the perceived medication-related burden among patients with multiple non-communicable diseases (NCDs), and to investigate the association between perceived burden and adherence to medication therapy. Medication-related burden was measured in three primary care clinics in Qatar using the Living with Medicines Questionnaire (LMQ) among adults with diabetes, with or without other comorbidities. Adherence was measured using the Adherence to Refills and Medications Scale (ARMS). Two hundred ninety-three eligible patients participated in the study. Majority of participants reported experiencing minimum (66.6%) to moderate (24.1%) medication-related burden. There was a significant positive correlation between the medication-related burden (measured by the LWQ) and medication adherence (measured by ARMS) (rs (253) = 0.317, p <0.0005). The duration of diabetes diagnosis, adherence score, marital status, employment status, and presence diagnosis of hypertension were significant predictors of medication burden. A considerable proportion of the patients in this study have reported experiencing medication-related burden. Healthcare providers should seek strategies to address this burden especially among patients with risk factors of cardiovascular diseases, non-adherent to their medication therapy, living alone, or non-employed.

Sleep postures monitoring systems in the hospital aim at transforming sensing signals into quantitative data to characterize the sleep behaviors of the patient. However, a home-care sleep posture monitoring system needs to be user friendly. In this paper, we present iSleePost - a user-friendly home-care intelligent sleep posture monitoring system. We address the labor-intensive labeling issue of traditional machine learning approaches in the training phase. Our proposed mobile health (mHealth) system leverages the communications and computation capabilities of mobile phones for provisioning a continuous sleep posture monitoring service. Our experiments show that iSleePost can achieve 90 percent accuracy in recognizing sleep postures. More importantly, iSleePost demonstrates that an easily-wear wrist sensor can accurately quantify sleep postures.

The function of sleep in mammal and other vertebrates is one of the great mysteries of biology. Many hypotheses have been proposed, but few of these have made even the slightest attempt to explain the essence of sleep - the uncompromising need for reversible unconsciousness. During sleep, epiphenomena - often of a somatic character - occur, but these cannot explain the core function of sleep. One answer could be hidden in the observations made for long periods of time of the function of the central nervous system (CNS). The CNS is faced with conflicting requirements on stability and excitability. A high level of excitability is desirable, and is also a prerequisite for sensitivity and quick reaction times; however, it can also lead to instability and the risk of feedback, with life-threatening epileptic seizures. Activity-dependent negative feedback in neuronal excitability improves stability in the short term, but not to the degree that is required. A hypothesis is presented here demonstrating how calibration of individual neurons - an activity which occurs only during sleep - can establish the balanced and highest possible excitability while also preserving stability in the CNS. One example of a possible mechanism is the observation of slow oscillations in EEGs made on birds and mammals during slow wave sleep. Calibration to a genetically determined level of excitability could take place in individual neurons during the slow oscillation, so that action potentials are generated during the oscillations “up-phase”. This can only take place offline, which explains the need for sleep. The hypothesis can explain phenomena such as the need for unconsciousness during sleep, with the disconnection of sensory stimuli, slow EEG oscillations, the relationship of sleep and epilepsy, age, the effects of sleep on neuronal firing rate and the effects of sleep deprivation and sleep homeostasis. This is with regard primarily to mammals, including humans, but also all other vertebrates.

Machine Learning (ML) approaches have been fruitfully applied to several classification problems of neurophysiological activity. Considering the relevance of emotion in human cognition and behaviour, ML found an important application field in emotion identification based on neurophysiological activity. Nonetheless, the literature results present a high variability depending on the neuronal activity measurement, the signal features and the classifier type. The present work aims to provide new methodological insight on ML applied to emotion identification based on electrophysiological brain activity. For this reason, we recorded EEG activity while emotional stimuli, high and low arousal (auditory and visual) were provided to a group of healthy participants. Our target signal to classify was the pre-stimulus onset brain activity. Classification performance of three different classifiers (LDA, SVM and kNN) was compared using both spectral and temporal features. Furthermore, we also contrasted the classifiers performance with static and dynamic (time evolving) features. The results show a clear increased in classification accuracy with temporal dynamic features. In particular, the SVM classifiers with temporal features showed the best accuracy (63.8 %) in classifying high vs. low arousal auditory stimuli.

Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)–cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch inducing expression of various antioxidative enzymes such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR–CYP1A1 signaling and activates the NRF2–antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR–CYP1A1 inhibition and NRF2 activation may be useful in managing dioxin-related health hazards.

A brand-new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this Unitarian perspective based upon that the hydrogen ion (H+) dynamics of cancer, allows understanding and integrating the many dualisms, confusions, and paradoxes of the disease. The new H+-related wide range model can embrace under a unique frame of mind the many aspects of the disease and at the same time therapeutically interfere with most, if not with all, the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC here reviewed may be beneficial for all types and stages of the disease. In this vein, we have attempted a mega synthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide range approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of a pH-related drugs nowadays available for the treatment of breast cancer is advanced.

This study aims to understand Filipino rice farmers’ aspirations, both farming and non-farming-related. Understanding aspirations can help the government and interested third-party entities to provide impactful initiatives to farmers. The Role Identity Theory guided our analysis in this study. This study is predominantly qualitative, with focus group discussion as the main method of collecting data. The research sites were in Kalinga, Nueva Ecija, Laguna, Quezon, Northern Samar, Zamboanga del Sur, Sultan Kudarat, and Agusan del Norte. Among the farming-related aspirations noted in this study relate to property, fair price, infrastructure, government support, and good governance. The non-farming related aspirations relate to infrastructure development; progress; government support and governance; love, passion, peace, and unity; wellness and long life.

Study Objective: This study examined office workstation types’ impact on objective health-related metrics including stress, physical activity (PA), and sleep quality. We propose a sensor-based sleep quality index (SB-SQI) to fill a needed gap for objective sleep quality measurement over short timescales. Methods: We monitored 231 office workers using chest-worn sensors for 72 hours, yielding 11,736 hours of usable data from 163 participants (mean age 43.4, 56% women). SB-SQI was based on a validated algorithm estimating sleep-onset latency, total sleep time, and sleep efficiency, using the scoring method from the Pittsburg Sleep Quality Index (PSQI). We examined the relationships between SB-SQI, office workstation type (open-bench seating, cubicle, and private office), work-hours stress (standard deviation of heart rate variability), and after-work PA (relative duration of moderate-to-vigorous activity). Results: The sensor-derived poor-sleep ratio of the private office workers was higher than with other office workstation types (81% vs. 66.1%, p = 0.023). PSQI revealed a similar but insignificant trend with a lower effect-size. Among good-sleepers, open-bench seating workers had 22% (p = 0.018) less stress during work hours than others. A significant association between work-hours stress and after-work hours PA (r = 0.331, p = 0.000) was observed irrespective of office workstation type, with the highest PA level observed for open-bench seating workers. Conclusions: Office workstation type had a significant impact on work-hours stress, affecting PA after work hours, which influenced sleep quality. SB-SQI could be more sensitive than PSQI in determining the impact of office workstation types on sleep quality.

Fear extinction requires coordinated neural activity within the amygdala and medial prefrontal cortex (mPFC). Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear extinction. Here, we investigated the effects of optogenetic manipulations of prelimbic (PrL) pyramidal neurons on amygdala gene expression to analyze the specific transcriptional pathways involved in adaptive and maladaptive fear extinction. To this aim, transgenic mice were (or not) fear-conditioned and during the extinction phase they received optogenetic (or sham) stimulations over PrL pyramidal neurons. At the end of behavioral testing, electrophysiological (neural cellular excitability and Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the PrL pyramidal neurons. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Our results show that the optogenetic activation of PrL pyramidal neurons in fear-conditioned mice induces fear extinction deficits, reflected in an increase of cellular excitability, excitatory neurotransmission, and spinogenesis of PrL pyramidal neurons, and in strong modifications of the transcriptome of amygdala pyramidal neurons. Understanding the electrophysiological, morphological and transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders.

The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Also, cannabidiol (CBD), the non-intoxicating component of Cannabis sativa, has been recently approved for treatment-resistant epilepsy. Seizures represent frequent medical comorbidities of ASD and could be responsible for the onset or worsening of behavioral problems. Thus, it has been hypothesized that cannabinoids could be useful in improving some ASD symptoms. Our systematic review was conducted according to the PRISMA guidelines and aimed to summarize the literature regarding the use of cannabinoids in ASD. After searching in Web of Knowledge^TM, PsycINFO, and Embase, we included ten studies (eight papers and two abstracts). Four ongoing trials were retrieved in ClinicalTrials.gov. Findings are promising, as cannabinoids appeared to improve problem behaviors, sleep, hyperactivity, and communication deficits, with limited cardiac and metabolic side effects. Interestingly, they generally allowed to reduce the number of prescribed medications and decreased the frequency of seizures in epileptic patients. Mechanisms of action could be linked to the excitatory/inhibitory imbalance found in people with ASD. However, further trials need to be implemented with better characterization and homogenization of samples, and well-defined outcomes.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

The interaction between endocannabinoid (eCB) system with in key brain structures such as hippocampus, amygdala and prefrontal cortex and sleep deprivation (SD)-induced psychosis has been less studied. The present hypothesis revolves around the question whether altered chemical dynamics within the eCB system with the resultant impact on cannabinoid receptors in key cortical hubs would impact SD-induced psychosis-like symptoms. Having this investigated research is expected to pave the path towards identifying newer drug targets namely for schizophrenia.

Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, protein sequences from sarbecoviruses were analyzed to identify highly-specific molecular markers consisting of conserved inserts or deletions (termed CSIs) in the spike (S) and nucleocapsid (N) proteins that are specific for either particular clusters/lineages of these viruses or are commonly shared by specific lineages. Three novel CSIs in the N-terminal domain of the spike protein S1-subunit (S1-NTD) are uniquely shared by the SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs, distinguishing this cluster of viruses (SARS-CoV-2r) from all others. In the same positions, where these CSIs are found, related CSIs are also present in two other sarbecoviruses (viz. CoVZXC21 and CoVZC45 forming CoVZC cluster), which form an out group of the SARS-CoV-2r cluster. These three CSIs are not found in the SARS-CoVs. However, both SARS and SARS-CoV-2r CoVs contain two large CSIs in the C-terminal domain of S1 (S1-CTD), which binds the human ACE-2 receptor, that are absent in the CoVZC cluster of CoVs. These results indicate that while the S1-NTD of the SARS-CoV-2r viruses possesses the sequence characteristics of the CoVZC cluster of CoVs, their S1-CTD resembles the SARS viruses. Thus, the spike protein of SARS-CoV-2r viruses has likely originated from a recombination event between the S1-NTD of the CoVZC viruses and the S1-CTD of SARS viruses. This inference is also supported by the amino acid sequence similarity of the S1-NTD and S1-CTD from SARS-CoV-2 compared to the CoVZC and SARS CoVs. We also present evidence that one of the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2, is also derived by a recent recombination between the S1-NTD of the CoVZC CoVs and the S1-CTD of a SARS-CoV-2 related virus. Several other identified CSIs are specific for others clusters of sarbecoviruses including a clade consisting of bat SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mappings studies show that the identified CSIs are located within surface-exposed loops and form distinct patches on the surface of the spike protein. These surface loops/patches are predicted to interact with other host components and play important role in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for the SARS-CoV-2r clade provide novel means for development of new diagnostic and therapeutic targets for these viruses.

：Sleep stage on the whole night is not steady. Sleepers generally pass through three to five cycles. In each cycle, there are occur four typical sleep stages, such as wake stage (WS), light stage (LS), deep sleep (DS), rapid eye movement sleep stage (REM). According to the natural routine, in this paper, we investigate the stage transition and analyze the feature of stage transition using the local cluster Algorithm (LCA). Two-cycle sleep model (TCSM) is proposed to automatically classify sleep stages using over-night continuous heart rate variability (HRV) data. The generated model is based on the characteristics of the nested cycle's sleep stage distribution and the transition probabilities of sleep stages. Experiments were conducted using a public data set including 400 healthy subjects (female 239, male 161) and the model’s classification accuracy was evaluated for four sleep stages: WS, LS, DS, REM. The experimental results showed that based on the TCSM model, the segmentation classification of pure sleep is 5.2% higher than that of the traditional method, and the accuracy of segmentation classification is 11.2% higher than the traditional sleep staging accuracy. The experimental performance is promising in terms of the accuracy, sensitivity, and specificity rates compared with the ones of the state-of-the-art methods. The study contributes to improve the quality of sleep monitoring in daily life using easy-to-wear HRV sensors.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Music and language are hypothesized to share neural resources, particularly at the level of syntax processing. Recent reports suggest that attention modulates this sharing of neural resources, but the time-course of the effects of attention, and the degree to which attention operates similarly on music and language, are yet unclear. In this EEG study we manipulate the syntactic structure of simultaneously presented musical chord progressions and garden-path sentences in a modified rapid serial visual presentation paradigm, while varying top-down attentional demands to the two modalities. The Early Right Anterior Negativity (ERAN) was observed in response to both attended and unattended musical syntax violations. In contrast, an N400 was only observed in response to attended linguistic syntax violations, and a P3 only in response to attended musical syntax violations. Results show that top-down allocation of attention indeed affects the processing of syntax in both music and language, with different neural resources acting upon the two modalities particularly at later stages of cognitive processing. However, the processing of musical syntax at an earlier stage of the perceptual-cognitive pathway, as indexed by the ERAN, is partially automatic, and is strongly indicative of separate neural resources for music and language.

Sleep deprivation (failure to get enough sleep) is a public health issue that can negatively impact our body including cognitive function. Many studies have been done in Saudi Arabia to evaluate the impact of poor sleep and academic performance but almost all of them were done at university level. To investigate the relationship between sleep quality and general degree of academic achievement in school students. This is a cross-sectional, school-based study, conducted at Jazan Region, Saudi Arabia. A total of 957 participants (615 male and 342 female) were recruited from a state school. The study used a standardized, confidential, validated self-administered questionnaire to assess sleep quality and habits. By using Statistical Package for Social Studies (SPSS 22), achievement of the students was significantly related to the following parameters; laziness and fatigue after wake-up time and during school time, lack of concentration during school time, difficulty in complete tasks during school time and inability to maintain wakefulness during school time. Furthermore, students with poor academic degrees reported more significant incidence of sleeping at school, excessive daytime sleepiness, and other sleep related disorder than good academic degrees. Students with poor sleep quality have lower school grades.

Late January 2020, COVID-19 unexpectedly imposed world-wide limitations on daily life. Deemed a pandemic mid-March 2020, lockdowns were imposed for an indefinite period, including at academic institutions. Consequently, interest in digital literacy—an on-going and increasing concern of academic institutions in the 21^st century—exponentially heightened. Continuing meetings of academic groups now necessitated online communication. In the almost overnight closure of all non-essential services, academic units at one post-secondary institution expeditiously selected Zoom—a popular video conferencing application—as the preferred platform for meetings until social distancing was lifted. In contrast to this widely accepted use of Zoom for scheduled meetings, one unique health-related group at the institution, tailored to the 4Cs of 21^st century learning of critical thought, communication, cooperation and creativity, found social networking through a private Facebook group a more appropriate and satisfying group experience than likely possible with the Zoom app. Pros and cons of both online platforms are presented along with when each choice is warranted. In promoting digital literacy as the primary goal in online communication for academic meetings, private Facebook groups hold promise for collaborative online academic meetings with similar features to this health-related group.

Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and its application in current clinical trials.

The variations in socioeconomic status (SES) between different social classes of a population correspond to differences in accessibility to all resources available and able to improve global health. While SES is now known as one of the main determinants for a good health and a good aging, its influence on sleep disorders (SD) is not well understood. SES is a concept, not directly observable but estimated using indicators like income, education, occupational status and area of living. This theoretical review explores some theories linking environment of people with occurrence of SD, with different patterns associated to SES. A model of interaction is proposed to summarize and conceptualizes these interactions and to promote more research on the topic.

The Nocturnal Bottleneck explains how mammals evolved from their reptilian ancestors after inverting the chronotype, form diurnal to nocturnal. Pre-mammals traded-off the excellent visual system of their ancestors for improvements in audition and in olfactory telencephalon, needed for efficient orientation in the dark. This was how the mammalian nocturnal telencephalic wakefulness was born. However, the modified visual system of those pre-mammals became sensitive to the dangerous diurnal light and the exposure would involve a high risk of blindness and death. Therefore, pre-mammals had to remain immobile with closed eyes hidden in lightproof burrows during light time. This was the birth of the mammalian sleep. Typical reptiles distribute their wake time cycling between Basking Behavior, to attain the preferred body temperature, and poikilothermic Goal Directed Behavior, to perform life sustaining tasks. These cycles persisted during the new mammalian sleep. However, as the behavioral output had to be blocked during light time, the paralyzed reptilian Basking Behavior and Goal Directed Behavior cycles became the NREM and REM cycles, respectively. This was how NREM and REM cycles remained incorporated within the mammalian sleep. After the Cretaceous-Paleogene extinction, the environmental pressure for nocturnal life was softened, allowing high variability in chronotype and sleeping patterns. This permitted some mammalian groups, e.g., primates, to begin the quest for diurnal wake.Concluding, sleep constituted an additional bottleneck in the mammalian evolution. The reduced population of pre-mammals that was able to develop sleep during light time, including NREM and REM, became full mammals and survived; the remainder perished.

As a result of the cancer immunotherapy revolution hundreds of clinical trials of the newly approved immunotherapies are now under way to improve responses. Not unexpectedly, the 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo for their development of cancer therapy by blockade of co-inhibitory signals. While success stories of terminal cancer patients achieving complete remissions are accumulating, not enough research has been done into the risks of the new therapies. Since the use of immunotherapy is becoming more common, and is expected to develop into first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the nemesis of immunotherapy. Immune-related adverse events (IrAEs) could affect any tissue, their incidence may reach up to 90% of patients and toxicity is dose-dependent. While the combination of two immune checkpoint inhibitors (ICIs) increased efficacy, the incidence of severe adverse events was also increased. Apparently, ICIs cannot be restricted to the targeted anti-tumor T cell population. The long lasting objective of cancer regression can only be achieved by paying a price: tolerance to healthy self tissues is compromised. In the face of an ipilimumab induced pan-lymphocytic activation, a therapeutic paradigm shift is required. The task is not desperately trying to put the genie back in the bottle by immune suppressive treatments, but instead harnessing the autoimmune forces by an off label low-dose combined anti-CTLA-4 and anti-PD1 antibody blockade, which is supplemented with conventional interleukin-2 stimulation and hyperthermia. The proof-of-principle of the low-dose-combination therapy was demonstrated in a heavily pre-treated triple negative breast cancer (TNBC) patient with far advanced pulmonary metastases and severe shortness of breath, who had exhausted all conventional treatment. Her pulmonary metastases went into complete remission with transient WHO I-II diarrhea and skin rash. She lived for 27 months after starting the low-dose-combination therapy. She had recurrence as a sternal mass and pleural metastases up to 3 cm. Since the low-dose-combination protocol consists only of approved drugs and treatments, this exceptional response should instigate further research efforts.

Despite the strong links between sleep, circadian rhythms, and mental health, sleep education has been neglected in mental healthcare provider training programs. The current pilot study examined the potential efficacy and acceptability of a sleep education workshop for trainee psychologists, called the Sleep Psychology Workshop. Eleven students completing their Master of Psychology degrees (90% female, 24.4 ± 1.6 years old) attended the Sleep Psychology Workshop as part of their Health Psychology course, delivered as three, two-hour lectures (total six hours). Trainees’ sleep psychology knowledge quiz scores (% correct) demonstrated significant improvement from pre- (M = 60%, SD = .09) to post-workshop (M = 79%, SD = .08), t (6) = -5.18, p = .002. Trainees also reported increased self-efficacy to use common sleep-related assessment instruments and empirically supported interventions to manage sleep and circadian rhythm disturbances, along with increased confidence to manage insomnia disorder in clinical practice (all p<.02). Trainees also endorsed the workshop as an acceptable sleep education program for trainee psychologists via a post-workshop feedback survey, focus group, and six-month follow-up survey. This pilot study provides preliminary evidence for the Sleep Psychology Workshop as an effective and acceptable sleep education program for trainee psychologists.

The objective of the study was to report the health-related quality of life (HRQOL) following road traffic accidents (RTAs) among children. A community-based survey using EuroQol five-dimension questionnaire (EQ-5D-5L) in Hindi was used to collected data from community. The survey included 2620 households from urban and rural areas of Ujjain, India. From these households 229 children aged 5–18 years with a history of RTA in the last 1 year were identified, with 27%, 63%, and 10% children reporting mild, moderate, and severe injury based on length of hospitalization. Motorcycles, bicycles, and pedestrians constituted most RTAs. Helmet use was low (12%). EQ-5D-5L revealed that the most severe and extreme problem was pain and discomfort, whereas the least severe problem was usual activity and self-care. The most common (65%) injuries were either abrasion or fracture and dislocation. EQ-5D-5L severity index was maximum (mean 72) for lower extremity injuries. The results of the present study highlight the ability and requirement for quality of life measurement using EQ-5D-5L among children post-RTA.

Telecommuting is a flexible form of work that has progressively spread over the last 40 years and which has been strongly encouraged by the measures to limit the Covid19 pandemic. There is still limited evi-dence on the effects it has on workers' health. In this survey we invited 905 workers of companies that made a limited use of telework to fill out a questionnaire to evaluate: Intrusive leadership of managers (IL), the request for work outside traditional hours (OFF-TAJD), workaholism (BWAS), effort / reward imbalance (ERI), happiness and common mental issues (CMIs), anxiety and depression, assessed by the Goldberg scale (GADS). The interaction between these variables has been studied by structural equation modeling (SEM). Intrusive leadership and working after hours were significantly associated with occu-pational stress. Workaholism is a relevant moderator of this interaction: intrusive leadership significantly increased the stress of workaholic workers. Intrusive leadership and overtime work were associated with reduced happiness, anxiety and depression. These results indicate the need to guarantee the right to disconnect, to limit the effect of the OFF-TAJD. In addition to this, companies should implement policies to prevent intrusive leadership and workaholism.

Background: Differential diagnosis between polymyalgia rheumatica (PMR) and seronegative elderly-onset rheumatoid arthritis (SEORA) is not easy, to the point that in the past they were considered the same entity. In these patients, sleep disorders have been scarcely assessed, and considered as expression of mood disorders such as depression and anxiety. Methods: In 38 Caucasian elderly patients (median age: 73.9 ± 8.06 years) consecutively referred to two outpatient clinics from January to May 2018 with diagnosis of PMR and SEORA, sleep impairment was assessed using the Medical Outcomes Study-Sleep scale (MOS-SS). Depression and anxiety were assessed using the Neuropsychiatric Inventory (NPI) score, with point 0 for absent and point 3 for severe. Comorbidities were assessed using the Cumulative Illness Rating Scale (CIRS). Patients taking medications used to treat sleep disturbance or that could favor sleep disturbances were excluded. The study was approved by the local ethics committee and carried out in accordance with the Helsinki Declaration, revised 2013. Every patient signed an informed consent form at the time of the first visit. Results: MOS-SS total point in PMR patients was significantly higher than in SEORA patients (47.60 ± 8.4 vs 28.26 ± 12.4; P = 0.000). After six-month therapy with prednisone (12.5–15 mg/day, followed after 4 weeks by gradual tapering), MOS-SS total point improved in the two groups of patients, with no significant difference (17.0 ± 6.2 vs 17.8 ± 4.2; P = 0.644). No correlation was found between MOS-SS and comorbidities, and between MOS-SS, anxiety or depression. Conclusions: Our data suggest that the assessment of sleep impairment could be very useful in the differential diagnosis between PMR and SEORA. Up today, the reasons why patients with PMR have—at the time of diagnosis—a sleep impairment higher than SEORA are speculative. Further ad hoc complementary studies in multicenter cohorts are needed.

Denture wearers often complain about jeopardized function and reduced quality of life due to lack of prosthesis’ retention. Implant retained mandibular overdentures, on 2 non-connected implants (2IOD) are well-proven solutions to overcome these issues. We prospectively assessed 69 patients and scrutinized clinical records until at least 7 years of function. Thirty-six were retained on Locator ® Abutments (LA) and thirty-tree on Ball Abutments (BA). Both systems were compared regarding the type, amount and total cost of required maintenance. One implants was lost, yielding 98.7% survival after 7 years. In total 438 technical issues occurred: 121 (27.35%) in BA and 317 (72.4%) in LA. Out of these, 343 events (78%) were solved chairside: 191 (43.6%) were replacements of retention caps, 113 (25.8%) were minor acrylic repairs, in 26 (5.9%) pressure ulcers had to be relieved and 13 (3%) related to abutments. LA required 179 insert replacements compared to 12 in the BA group. The overall initial treatment cost was 3850 euro. The average total maintenance cost in relation to the initial cost for the LA and BA groups was 19.11% (range 0% - 82.24%) and 18.91% (range 0% - 113.26%) respectively (P=0.540). Conclusions: The 7-years maintenance costs for a 2IOD is acceptable when the patient is regularly checked and professionally maintained. Most events are easily solvable chairside, but a few patients required more expensive interventions, regardless of the type of attachment used.

A practical method is presented to estimate rare earth elements (REE) concentrations in magmatic vapour phase (MVP) in equilibrium with water-saturated granitic melts based on empirical fluid-melt partition coefficients of REE (k_P^REE). The values of k_P^REEcan be calculated from a set of new polynomial equations linking to the chlorine molality (m_Cl^v) of the MVP associated with granitic melts, which are established via a statistical analysis on the existing experimental dataset. These equations may be applied to the entire pressure range (0.1 to 10.0 kb) within the continental crust, suggesting that light REEs behave differently in magmatic fluids, i.e. either being fluid compatible with higher m_Cl^v or fluid incompatible with lower m_Cl^v values. In contrast, heavy REEs are exclusively fluid incompatible and partition favourably into granitic melts. Consequently, magmatic fluids tend to be rich in LREE relative to HREE, leading to REE fractionation during the evolution of magmatic hydrothermal systems. Maximum k_P^REEvalue for each element is predicted and presented in a REE distribution diagram constrained by the threshold of m_Cl^v. REE contents of the granitic melt is approximated by whole-rock analysis, so that REE concentrations in the associated MVP would be estimated from the value of k_P^REE given chemical equilibrium retains. Two examples are provided respectively, to show the use of this method as a REE tracer to fingerprint the source of ore-fluids responsible for the Lake George intrusion-related Au-Sb deposit in New Brunswick (Canada), and for the Bakircay Cu-Au (-Mo) porphyry systems in northern Turkey.

Adolescence is a critical developmental period associated with an increase in stress, the appearance of anxiety and depressive symptoms, and changes in sleep patterns. Even though the disruption of sleep patterns in stress and anxiety and depressive disorders is well known, the independent effects of childhood trauma and stressful life events on sleep patterns are less understood. We tested the independent effects of stress (childhood trauma and stressful life events) while controlling for anxiety and depression on adolescent sleep patterns. Seven hundred fifty-two adolescents completed self-report questionnaires about childhood trauma, stressful life events, anxiety, and depression. Four sleep factors identifying movement during sleep, sleep regularity, sleep disturbances and sleep pressure were extracted in the principal component analysis of sleep questions. Both childhood trauma and recent stressful life events were significantly associated with sleep disturbances before and after controlling for anxiety and depression.

Background: The mortality and severity in COVID-19 is increased in patients with comorbidities. The aim of this study was to evaluate the unknown risk of severity and mortality in COVID-19 patients with underlying kidney and liver diseases. Method: We retrieved data on the clinical features and primary composite end point of COVID-19 patients released from inception till 16^th of April 2020 from Medline and Embase. The data on two comorbidities, liver diseases and chronic kidney disease, present in COVID-19 were pooled and statistically analysed to explain the associated severity and mortality rate. Results: 142 abstracts were screened, and 41 full articles were then read. In total, 22 studies including 5595 COVID-19 patients were included in this study with case fatality rate of 16%. The prevalence of liver diseases and CKD were 3% (95%CI; 2%-3%) and 1% (95%CI; 1%-2%) respectively. In patients with COVID-19 and underlying liver diseases, 57.33% (43/75) cases were severe with 17.65% mortality. While in CKD patients with COVID-19, 83.93% (47/56) severity and 53.33% (8/15) mortality were reported. Conclusion: This study found an increased risk of severity and mortality in COVID-19 patients with liver diseases and CKD. This will allow for better clinical management and inform more stringent preventative measures for this group of patients.

Deregulation of cell growth and development lead to cancer, a severe condition that claims millions of lives worldwide. Targeted or selective approaches used during cancer treatment determine the efficacy and outcome of the therapy. In order to enhance specificity and targeting and better treatment options for cancer, novel and alternative modalities are currently under development. Photodynamic therapy has the potential to eradicate cancer and combination therapy would yield even greater outcomes. Nanomedicine-aided cancer therapy shows enhanced specificity for cancer cells and minimal side-effects coupled with effective cancer destruction both in vitro and in vivo. Nanocarriers used in drug-delivery systems are well able to penetrate cancer stem cell niche, simultaneously killing cancer cells and eradicate drug-resistant cancer stem cells, yielding therapeutic efficiency up to 100 fold against drug-resistant cancer in comparison with free drugs. Safety precautions should be considered when using Nano-mediated therapy as the effects of extended exposure to biological environments are still to be determined.

This study aims to develop a performance evaluation system that can facilitate performance evaluation at region, hospital, and department levels to enable better cost management for sustainable development. A multi-level system of performance evaluation informs a hierarchical assessment of cost management from regions to hospitals to departments using diagnosis-related group (DRGs). Various metrics are developed employing the variances between targets and actuals where targets are determined from two perspectives: benchmarking using external regional prices and change management using internal data. Targets for the latter are statistically based and specifically incorporate variability. The model is applied to two hospitals, twenty departments, nine DRGs and 1071 inpatients. The analyses indicate that the approach can provide a practical evaluation tool that allows for particular characteristics at multiple levels. The system provides macro-micro and external-internal perspectives in performance, enabling high-level variances to be decomposed thereby identifying sources of performance variability and financial impact.

Limited observational studies have described the relationship between sleep duration and overall diet. The present study investigated the association between sleep duration at weekdays and empirically derived dietary patterns in a nationally representative sample of UK adults, aged 19-64 years old, participating in the 2008-2012 UK National Diet and Nutrition Survey Rolling Programme. Survey members completed between three to four days of dietary records. Sleep duration at weekdays was categorised into tertiles to reflect short, normal and long sleep duration. Social jetlag was calculated as the difference between sleep duration at weekends and weekdays. The association between sleep duration/ social jetlag and dietary patterns, derived by principal components analysis, was assessed regressing diet on sleep whilst accounting for the complex survey design and adjusting for relevant confounders. Survey members in the highest tertile of sleep duration had on average 0.45 (95% CI -0.78, -0.12) lower healthy dietary pattern score compared to middle tertile (p =0.007). There was an inverted u-shaped association between social jetlag and a healthy dietary pattern, such that when sleep at weekends exceeded weekday sleep by 1h 45min, scores for indicating a healthy dietary pattern declined (p =0.005). In conclusion, long sleep duration at weekdays and an increased social jetlag are associated with a lower healthy dietary pattern score. Further research is required to address factors influencing dietary patterns in long sleepers.

Background. Wnt-pathway proteins play a vital role in kidney development and defects in the Wnt-pathway are associated with kidney disorders. However, the knowledge on the role of Wnt/β-catenin pathway proteins in end-stage renal disease (ESRD) is limited.Aim of the study. To delineate the association of ESRD and Wnt-proteins including the agonistR-spondin 1, the transducer β-catenin and the antagonists Dickkopf-related protein 1 (DKK1) and sclerostin.Methods. Serum Wnt-pathway proteins levels were measured by ELISA, while other biochemicals were measured spectrophotometrically in 60 ESRD patients and 30 normal controls.Results. DKK1 and sclerostin were significantly higher in ESRD than in controls, and β-catenin and the catenin + R-Sponin-1 / DKK1 + sclerostin ratio, reflecting the ratio of agonist and transducer on antagonists (AT/ANTA), were significantly lower in ESRD. Logistic regression analysis showed that ESRD was significantly predicted by increased levels of DDK1 and sclerostin and lowered β-catenin (p<0.001). eGFR was significantly associated with DKK1 and sclerostin (inversely), β-catenin (positively) and the AT/ANTA ratio (r=0.468, p<0.001). DKK1 levels were significantly and positively correlated with urea, creatinine, and copper. DKK1 and sclerostin were inversely associated with hemoglobin and packet cell volume. Catenin was significantly negatively associated with copper, urea and creatinine.Conclusion. Wnt/β-catenin pathway proteins show significant alterations in ESRD, indicating significantly increased levels of antagonists and, therefore, attenuated Wnt/β-catenin pathway activity. The latter is associated with lowered eGFR and increased serum copper levels. Wnt/β-catenin pathway proteins are possible drug targets to treat ESRD or its consequences.

One of the major unsolved mysteries of biological science concerns the question of where and in what form information is stored in the brain. I propose that memory is stored in the brain in a mechanically encoded binary format written into the conformations of proteins found in the cell-extracellular matrix adhesions that organise each and every synapse. The MeshCODE framework outlined here represents a unifying theory of data storage in animals, providing read-write storage of both dynamic and persistent information in a binary format. Mechanosensitive proteins that contain force-dependent switches can store information persistently, which can be written or updated using small changes in mechanical force. These mechanosensitive proteins, such as talin, scaffold each synapse, creating a meshwork of switches that together form a code, the so-called MeshCODE. Large signalling complexes assemble on these scaffolds as a function of the switch patterns and these complexes would both stabilise the patterns and coordinate synaptic regulators to dynamically tune synaptic activity. Synaptic transmission and action potential spike trains would operate the cytoskeletal machinery to write and update the synaptic MeshCODEs, thereby propagating this coding throughout the organism. Based on established biophysical principles, such a mechanical basis for memory would provide a physical location for data storage in the brain, with the binary patterns, encoded in the information-storing mechanosensitive molecules in the synaptic scaffolds, and the complexes that form on them, representing the physical location of engrams. Furthermore, the conversion and storage of sensory and temporal inputs into a binary format would constitute an addressable read-write memory system, supporting the view of the mind as an organic supercomputer.

Overweight and obesity adversely affect health-related quality of life (HRQOL) through day-to-day impairments of both mental and physical functioning. It is assumed that polyphenols within the Mediterranean diet may contribute to improve HRQOL. This investigation aimed at studying the effects of a polyphenol-rich ingredient on HRQOL in overweight and obese but otherwise healthy individuals. A randomized, double-blind, placebo-controlled study including 72 volunteers was conducted. Subjects were randomly assigned to receive for a 16-week period either 900 mg/day of the supplement or a placebo. Dietary recommendations were individually determined, and intakes were recorded; daily physical mobility was monitored. Improvement of HRQOL was set as the primary outcome and assessed at baseline and at the end of the investigation, using the Short-Form 36 (SF-36) Health survey. Body composition was analyzed using dual-energy X-ray absorptiometry (DXA). Physical activity level was calculated using International Physical Activity Questionnaire (IPAQ). After 16 weeks, despite there was no adherence to the Mediterranean Diet Serving Score (MDSS), supplemented individuals experienced significant HRQOL improvement (+5.3%; P=0.001), including enhanced perceived physical (+11.2%; P=0.002) and mental health (+4.1%; P=0.021) components; bodily pain, vitality, and general health, being the greatest contributors. Besides, body fat mass significantly decreased (-1.2 kg; P=0.033), mainly within trunk area (-1.0 kg; P=0.002). Engagement in physical activity significantly increased (+1308 Met-min/week; P=0.050). Hence, chronic supplementation with a nutritional diversity and dose of a Mediterranean diet-inspired polyphenol-rich ingredient resulted in a significant amelioration in both perceived physical and mental health, concomitant with the improvement of body composition, in healthy subjects with excessive adiposity.

Pulse oximetry is the current standard for detecting drops in arterial blood oxygen saturation (SpO₂) associated with obstructive sleep apnea and hypopnea events in polysomnographic (PSG) testing. In cases of hypoxic challenge, such as occurs during apneic events, regulatory mechanisms restrict blood flow to the skin to preferentially maintain SpO₂ for more vital organs. As a result, a measure related to skin tissue oxygenation is likely to be more sensitive to inadequate breathing during sleep than pulse oximetry. Energy Conversion Monitoring (ECM) provides a method for measuring skin tissue oxygen-dependent energy conversion and, as such, is promising for more sensitively detecting sleep disordered breathing (SDB) events compared to pulse oximetry. We hypothesized that ECM would detect hypoxia occurring with SDB events associated with drops in SpO₂ but also would detect hypoxic challenge occurring with SDB events not associated with drops in SpO₂ (hypopneas defined by a drop in nasal pressure occurring in conjunction with an arousal, respiratory-related arousals, and primary snoring). Primary snoring is of particular interest with respect to the potential of ECM because it is statistically associated with co-morbidities of SDB, such as hypertension, but is not considered pathological because of the lack of a proximal measure of pathology occurring with PSG. In this article we review ECM technology and methodology, present preliminary data indicating that it detects hypoxia occurring in the skin during SDB events that is not detected as blood desaturation by pulse oximetry, and make the case that it is a promising tool for identifying pathology occurring at the mild end of the SDB spectrum.

Despite concerns about the negative effects of social distancing and prolonged school closures on children’s lifestyle and physical activity (PA) during the COVID-19 pandemic, robust evidence is lacking on the impact of the COVID-19 pandemic on children’s wellbeing and daily life. This study aimed to examine changes in the PA levels, sleep patterns and screen time of school-aged children during the different phases of COVID-19 outbreak in Hong Kong using a repeated cross-sectional design. School students (Grades 1 to 12) were asked to report their daily electronic device usage and to fill in a sleep dairy recording their daily sleep and wake-up time. They were equipped with a PA monitor, Actigraph wGT3X-BT, to obtain objective data on their PA levels and sleep patterns. Students were recruited before the pandemic (Sep 2019 – Jan 2020; n=577), during school closures (Mar 2020 – Apr 2020; n=146), and after schools partially reopened (Oct 2020 – Jul 2021; n=227). Our results indicated lower PA levels, longer sleep duration, and longer screen time among participants recruited during school closures than those recruited before the COVID-19 outbreak. Primary school students were found to sleep on average for an extra hour during school closures. Our findings illustrate the impact of social distancing policies during the COVID-19 pandemic on the sleep pattern, screen time, and PA level in school-aged children in Hong Kong. Professionals should reinforce the importance of maintaining a physically active lifestyle, good sleep hygiene, and healthy use of electronic devices to parents and school-aged children during the COVID-19 Pandemic.

In recent decades, organizational research has given special attention to the mechanisms promoting the health and wellbeing of nursing professionals. In this context, self-esteem is a personal resource which influences wellbeing at work and psychological wellbeing of nurses. The purpose of this study was to analyze the mediating role of eating in the effect of sleep quality on self-esteem in nursing professionals. The sample of 1073 nurses were administered the Rosenberg General Self-Esteem Scale, the Pittsburgh Sleep Quality Index and the Three-Factor Eating Questionnaire-R18. The results show that poor sleep quality and type of eating directly and indirectly affect self-esteem. More so, poor sleep quality deteriorated self-esteem through emotional eating, and even though emotional eating facilitated disinhibited eating, this relationship had no significant effects on self-esteem. The findings of this study suggest that hospital management should implement employee health awareness programs on the importance of healthy sleep and design educational interventions for improving the quality of their diet.

The combined ecological, geophysical, climatic, and social factors of the Northeast of Russia influence the organism from the early childhood being too intense for the functional systems. The purpose of the research is to study the emotional characteristics of adolescents of different ethnic groups in the northeast of Russia. Presented in the paper are results of the study that covered 826 adolescents (445 females and 381 males) at the age of 15–17, different by ethnic origin. We used standard methods of psycho-diagnostics. Our study has showed that the formation of the adolescents’ emotional sphere in the North is undoubtedly influenced not only by the climatic and socio-economic environmental factors but also by ethnic features. There are intergroup differences in the aggressiveness profile of older adolescents living in the remote settlement vs. the regional center. It is shown that high school students in the remote settlement of Evensk, compared to their peers in Magadan, regardless of gender and ethnicity, are characterized by more pronounced hostile and auto-aggressive reactions. In adolescents of the Aboriginal population, as compared with their age mate Caucasians, the indicators of impairment in the field of Neuro Psychic Adaptation, Situational and Personal Anxiety, and Social Frustration are significantly more pronounced.

Objective: Diabetes is associated with increased cardiovascular and cerebrovascular disease-related mortality. We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), total and active glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). Methods: This study consisted of four groups in Medicine Hospital between April- October, 2017: Control group (mean ages: 50.3 ± 10.7 years, 20 females and 15 males), diabetic group (DM) (mean ages: 53.9 ± 11.1, 14 females and 23 males), CAD group (mean ages: 62.6 ± 11.8, 17 females and 17 males) and CAD+ DM group: (mean ages: 62.6 ± 11.8 years, 18 females and 18 males). Results: Both CAD and CAD+DM groups have higher CIMT levels than controls. CAD+DM group have also significantly higher CIMT levels than DM group. Left external carotid artery (ECA) was only found different in DM group from controls. When compared with controls, DM, CAD groups have low DPP-4 and GLP-1_total concentration. Control group have significantly lower SFRP-4 levels than DM, CAD and CAD+DM (p<0.001) groups. Serum GLP-1_total levels were found to be significantly low in CAD+DM group when compared to control group. Conclusion: DPP-4 and SFRP-4 levels are predictive marker for atherosclerosis in diabetes, correlates well with HOMA-IR particularly in diabetes. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD. Large cohorts and at-risk populations are needed to confirm the predictive value of these findings.

The mechanization of agricultural activities has led to indiscriminate deposition of toxic xenobiotics, including organophosphates in the biomes, and this has led to intoxication characterized with deleterious oxidative and neuronal changes. This study investigated the consequences of oxidative and neurogenic disruptions that follow exposure to two organophosphates, chlorpyrifos (CPF) and dichlorvos (DDVP) on neuro-cognitive performance and anxiety-like behaviors in rats Thirty-two adult male Wistar rats (150 – 170g) were randomly divided into 4 groups, orally exposed to normal saline (NS), DDVP (8.8mg/kg), CPF (14.9mg/kg) and DDVP+CPF for 14 consecutive days. On day 10 of exposures, anxiety-like behaviors and amygdala dependent fear learning were assessed using Open Field and Elevated Plus Maze paradigms respectively, while spatial working memory was assessed on day 14 in the Morris water maze paradigm, following 3 training trials each on days 11, 12 and 13. On day 15, the rats were euthanized, and their brains excised, hippocampus and amygdala removed, 5 of which were homogenized and centrifuged to analyze nitric oxide (NO) metabolites, total reactive oxygen species (ROS), and acetylcholinesterase (AChE) activity, and the other three processed for histology (cresyl violet stain) and proliferative marker (Ki67 immunohistochemistry). Marked (p≤0.05) loss in body weight, AChE depletion, and overproduction of both NO and ROS were observed after repeated exposure to individual and combined doses of CPF and DDVP. Insults from DDVP exposure appeared more severe owing to the observed greater losses in the body weights of exposed rats. There was also a significant (p≤0.05) effect on the cognitive behaviors recorded from the exposed rats, and these deficits were related to the oxidative damage and neurogenic cell loss in the hippocampus and the amygdala of the exposed rats. Taken together, these results provided an insight that oxidative and neurogenic damages are central to the severity of neuro-cognitive dysfunction and increased anxiety-like behaviors that follow organophosphate poisoning.

Leucokinins (LKs) constitute a family of neuropeptides identified in numerous insects and many other invertebrates. The LKs act on G-protein coupled receptors that display only distant relations to other known receptors. In adult Drosophila, 26 neurons/neurosecretory cells of three main types express LK. The four brain interneurons are of two types, and these are implicated in several important functions in the fly’s behavior and physiology, including feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. The 22 neurosecretory cells (ABLKs) of the abdominal neuromeres coexpress LK and a diuretic hormone (DH44), and together these regulate water and ion homeostasis and associated stress, as well as food intake. In Drosophila larvae, LK neurons modulate locomotion, escape responses, and aspects of ecdysis behavior. A set of lateral neurosecretory cells, ALKs, in the brain express LK in larvae, but inconsistently so in adults. These ALKs coexpress three other neuropeptides and regulate water and ion homeostasis, feeding and drinking, but the specific role of LK is not yet known. This review summarizes Drosophila data on embryonic lineages of LK neurons, functional roles of individual LK neuron types, interactions with other peptidergic systems, and orchestrating functions of LK.

It has been widely described that chronic intake of fructose causes metabolic alterations which can be associated with brain function impairment. In this study, we evaluated the effects of fructose intake on the sleep-wake cycle, locomotion and neurochemical parameters in Wistar rats. The experimental group was fed with 10% fructose in drinking water for five weeks. After treatment, metabolic indicators were quantified in blood. Electroencephalographic recordings were used to evaluate the sleep architecture and the spectral power of frequency bands. Likewise, the locomotor activity and the concentrations of orexin A and monoamines were estimated. Our results show that fructose diet significantly increased the blood levels of glucose, cholesterol, and triglycerides. Fructose modified the sleep-wake cycle of rats increasing the waking duration and conversely decreasing the non-rapid eye movement sleep. Furthermore, these effects were accompanied by increases of the spectral power at different frequency bands. Chronic consumption of fructose caused a slight increase in the locomotor activity as well as an increase of orexin-A and dopamine levels in the hypothalamus and brainstem. Specifically, immunoreactivity for orexin-A was increased in the ventral tegmental area after the intake of fructose. Our study suggests that fructose induces metabolic changes and stimulates the activity of orexinergic and dopaminergic neurons which may be responsible for alterations of the sleep-wake cycle.

Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina, and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo, and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested, to be more sensitive and specific for imaging spectral char-acteristics of lipofuscin fluorescence.

In March 2020 the World Health Organization declared the “pandemic state” due to COVID-19 imposing strict confinement of the world population. People were forced to spend more time at home, changing some daily routines, including social interactions, the possibility to perform sports, and diet habits. These changes could exert a greater impact on patients suffering from chronic diseases, such as endocrine patients. This study aimed to assess the effects of Covid-19 induced quarantine on daily habits in a group of patients with endocrine disorders, focusing on food consumption, eating, and sleep habits during the confinement. Eighty-five endocrine patients were enrolled. A structured interview was administered investigating: socio-demographic information, general medical conditions and habits adopted during the quarantine. All patients underwent the Spielberger State Anxiety Inventory (STAI-Y1) to assess state anxiety. Subjects had mainly a sedentary lifestyle. We found a significant increase in the number of cigarettes in smokers, an increase of meals consumed during the confinement and a high rate of sleep disorder occurrence, especially insomnia. The changes of daily habits were, probably, due to the alterations of routine, that determined more bore and inactivity during the day.

When we are asleep we lose the ability to promptly respond to external stimuli and yet we spend many hours every day in this inherently risky behavioral state. This simple fact strongly suggests that sleep must serve essential functions that rely on the brain going offline, on a daily basis, and for long periods of time. If these functions did not require partial sensory disconnection, it would be difficult to explain why they are not performed during waking. Paradoxically, despite its central role in defining sleep and what sleep does, sensory disconnection during sleep remains a mystery. We have a limited understanding of how it is implemented along the sensory pathways, we do not know whether the same mechanisms apply to all sensory modalities, nor do we know to which extent these mechanisms are shared between non-rapid eye movement (NREM) sleep and REM sleep. The main goal of this contribution is to review some knowns and unknowns about sensory disconnection during sleep as a first step to fill this gap.

EZH2 overexpression is associated with tumor proliferation, metastasis, and poor prognosis. Targeting and inhibiting EZH2 may be an effective therapeutic strategy for head and neck squamous cell carcinoma (HNSCC). We previously analyzed EZH2 mRNA expression in a well-characterized dataset of 230 (110 original and 120 validation cohorts) human head and neck cancer samples. This study aimed to investigate the effects of inhibiting EZH2, either via RNA interference or via pharmacotherapy, on HNSCC growth. EZH2 upregulation was significantly correlated with recurrence (P < 0.001) and the methylation index of tumor suppressor genes (P < 0.05). DNMT3A was significantly upregulated upon EZH2 upregulation (P = 0.043). Univariate analysis revealed that EZH2 upregulation was associated with poor disease-free survival (log-rank test, P < 0.001). In multivariate analysis, EZH2 upregulation was evaluated as a significant independent prognostic factor of disease-free survival (hazard ratio: 2.085, 95% confidence interval: 1.390–3.127; P < 0.001). Cells treated with RNA interference and DZNep, an EZH2 inhibitor, showed the most dramatic changes in expression, accompanied with a reduction in the growth and survival of FaDu cells. These findings suggest that EZH2 upregulation is correlated with tumor aggressiveness and adverse patient outcomes in HNSCC. Evaluation of EZH2 expression might help predict the prognosis of HNSCC patients.

Inside Central Nervous System (CNS) appears neurons and glia cells. There are more glial cells than neurons and have more functions than neurons. Glia name represents different kind of cells, ones from neural origin (astrocytes, radial glia, and oligodendroglia), and others from blood monocytes (microglia). During ontogeny, neurons appear first (rat fetal 15th) and after astrocytes (rat fetal 21th) indicating a bigger importance function in the CNS. Also, during the phylogeny, reptiles have less astrocytes compared to neurons and in humans, astrocytes are double in number than neurons. This data, perhaps means that astrocytes are more special cells and work in memory and learning? Astrocytes have an important role in different mechanisms protecting CNS across the production of antioxidant and anti-inflammatory proteins, cleaning extracellular medium and helping neurons to communicate with each other correctly. Inflammatory mediators production are important to prevent changes in normal physiology. But, excessive or continue production leads to many diseases, such as Alzheimer's disease (AD), Sclerosis Lateral Amyotrophic (ELA), Multiple sclerosis (MS), and neurodevelopment diseases, like Bipolar disorder, Schizophrenia, and Autism's symptomatology. Different drugs and thecniques can reverse oxidative stress and/or inflammatory excess. This review is intended to serve as an approximation to the field.

Background: Sleep deficiency can adversely affect the performance of resident physicians resulting in greater medical errors. However, the impact of sleep deficiency on surgical outcomes, particularly among attending surgeons is less clear. Methods: Sixty attending surgeons from academic and community departments of surgery or obstetrics and gynecology were studied prospectively using direct observation and self-report to explore the effect of sleep deprivation on patient safety, operating room communication, medical errors, and adverse events while operating under two conditions, Post-Call (defined as >2 hours of nighttime clinical duties) and Non-Post-Call. Results: Each surgeon contributed up to five surgical procedures post-call and non-post-call yielding 362 cases total (150 Post-Call and 210 Non-Post-Call). Most common were caesarian section and herniorrhaphy. Hours of sleep on the night before the operative procedure were significantly less Post-Call (4.98 ± 1.41) vs. Non-Post-Call (6.68 ± 0.88, p<0.01). Errors were infrequent and not related to hours of sleep or post-call status. However, Non-Technical Skills for Surgeons (NOTSS) ratings demonstrated poorer performance while Post-Call for Situational Awareness, Decision Making and Communication/Teamwork. Fewer hours of sleep also was related to lower ratings for Situational Awareness and Decision Making. Decreased self-reported alertness was observed to be associated with increased procedure time. Conclusions: Sleep deficiency in attending surgeons was not associated with greater errors during procedures performed during the next day. However, procedure time was increased suggesting that surgeons were able to compensate for sleep loss by working more slowly. Ratings on non-technical surgical skills were adversely affected by sleep deficiency.

Commercial sleep devices and mobile-phone applications for scoring sleep are gaining ground. In order to provide reliable information about the quantity and/or quality of sleep, their performance needs to be assessed against the current gold-standard, i.e. polysomnography (PSG; measuring brain, eye and muscle activity). We here assessed some commercially available sleep trackers, namely; a commercial activity tracker: Mi band (Xiaomi, BJ, CHN), a scientific actigraph: Motionwatch 8 (CamNTech, CB, UK), and a much used sleep application: Sleep Cycle (Northcube, GOT, SE). We recorded 27 nights in healthy sleepers using PSG and these devices. Surprisingly, all devices had very poor agreement with the gold standard. Sleep parameter comparisons revealed that specifically the Mi band and the sleep cycle application had difficulties in detecting wake periods which negatively affected the total sleep time and sleep efficiency estimations. However, all 3 devices were good in detecting the most basic parameter, the actual time in bed. In summary, our results suggest that, to-date; available sleep trackers do not provide meaningful sleep analysis but may be interesting for simply tracking times in bed. A much closer interaction with the scientific field seems necessary if reliable information shall be derived from such devices in the future.

Mastocytosis is characterized by pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier’s sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.

Environmental studies, metabolic research, and state of the art neurobiology point towards the reduced amount of natural day and sunlight exposure of the developing child’s organism as the consequence of increasingly long hours spent indoors online as the single unifying source of a whole set of health risks identified worldwide, as is made clear in this review of the current literature. Over exposure to digital environments, from abuse to addiction, now concerns even the youngest (ages 0 to 2), and triggers, as argued on the basis of clear examples herein, a chain of interdependent negative and potentially long-term metabolic changes. This leads to a deregulation of the serotonin and dopamine neurotransmitter pathways in the developing brain, currently associated with online activity abuse and/or internet addiction, and akin to that found in severe substance abuse syndromes. A general functional working model is proposed under the light of evidence brought to the forefront in this review.