Objectives Night work is associated with several negative health outcomes as well as accidents and reduced productivity. The aim of this study was to identify factors that may counteract the negative effects of night work. 

Methods We conducted searches for studies of scientifically based countermeasures of the negative effects of night work in PubMed and Thomson Reuters’ ISI Web of Knowledge© and inspected the reference lists of relevant literature. 

Results We identified studies describing countermeasures such as proper personnel selection, bright light therapy, melatonin administration, naps, exercise, sleepiness detection devices, and the use of stimulants to improve wakefulness and hypnotics to improve daytime sleep. 

Conclusions There is some research supporting countermeasures (eg, bright light, melatonin, naps, use of stimulants, proper work scheduling) as a means to improve adaptation to night work. However, there is little evidence that such countermeasures reduce the long-term health consequences of night work. Future studies should aim at identifying both work and individual factors which are related to differential health outcomes of night work. Better study designs (eg, longitudinal designs and use of standardized outcome measures) are needed in future research.

https://www.jstor.org/stable/info/40967837

Measures to counteract the negative effects of night work

This study was conducted to evaluate the prevalence of daytime sleepiness and evening chronotype and to assess the extent to which both are associated with the use of caffeinated stimulants among 3,000 Thai college students. Demographic and behavioral characteristics were collected using a self-administered questionnaire. The Epworth Sleepiness Scale and the Horne and OstbergMorningness-Eveningness Questionnaire were used to evaluate prevalence of daytime sleepiness and circadian preference. Multivariable logistic regression models were used to evaluate the association between sleep habits and consumption of caffeinated beverages. Overall, the prevalence of daytime sleepiness was 27.9% (95% CI: 26.2 to 29.5%) while the prevalence of evening chronotype was 13.0% (95% CI: 11.8 to 14.2%). Students who use energy drinks were more likely to be evening types. For instance, the use of M100/M150 energy drinks was associated with a more than 3-fold increased odds of evening chronotype (OR 3.50; 95% CI 1.90 to 6.44), while Red Bull users were more than twice as likely to have evening chronotype (OR 2.39; 95% CI 1.02 to 5.58). Additionally, those who consumed any energy drinks were more likely to be daytime sleepers. For example, Red Bull (OR 1.72; 95% CI 1.08 to 2.75) or M100/M150 (OR 1.52; 95% CI 1.10 to 2.11) consumption was associated with increased odds of daytime sleepiness. Our findings emphasize the importance of implementing educational and prevention programs targeted toward improving sleep hygiene and reducing the consumption of energy drinks among young adults.

	Key words: Daytime sleepiness, Caffeine, stimulants, college students, morningness-eveningness.

/pdf/daytime-sleepiness-circadian-preference-caffeine-consumption-4m2zgvqai3.pdf

Daytime Sleepiness, Circadian Preference, Caffeine Consumption and Use of Other Stimulants among Thai College Students.

Rationale
Evidence is emerging that positive and negative modulation of the metabotropic glutamate (mGluR5) receptors has the potential for treating cognitive deficits and neuroprotection associated with psychiatric and neurodegenerative diseases, respectively. Sleep and synchronisation of disparate neuronal networks are critically involved in neuronal plasticity, and disturbance in vigilance states and cortical network connectivity contribute significantly to cognitive deficits described in schizophrenia and Alzheimer’s disease. Here, we examined the circadian changes of mGluR5 density and the functional response to modulation of mGluR5 signaling.

Negative versus positive allosteric modulation of metabotropic glutamate receptors (mGluR5): indices for potential pro-cognitive drug properties based on EEG network oscillations and sleep-wake organization in rats.

SUMMARY Aims: Safranal (2,6,6-trimethyl-1,3-cyclohexadiene-1-carboxaldehyde, C10H14O) is an active ingredient in the saffron, which is used in traditional medicine. It has been reported to have sedative and anti-epileptic effects, but its hypnotic effects remain uncertain. The aim of this study was to evaluate effects of safranal on sleep-wake cycle. Methods: We established hypnotic-model mice treated with a low dose of pentobarbital 20 mg/kg, and administered different doses of safranal, vehicle, or diazepam. The change of sleep-wake cycle was assessed by sleep recording and c-Fos expression in the brain was analyzed by immunohistochemistry. Results: Safranal increased the duration of non-rapid eye movement (NREM) sleep, shortened NREM sleep latency, and enhanced the delta power activity of NREM sleep. Immunohistochemical evaluation revealed that safranal increased c-Fos expression in the ventrolateral preoptic nucleus (VLPO), one of the putative sleep centers, and decreased it in the arousal histaminergic tuberomammillary nuclei (TMN). Conclusion: These findings indicate that safranal enhances NREM sleep in pentobarbital-treated mice. The hypnotic effects of safranal may be related to the activation of the sleep-promoting neurons in the VLPO and the simultaneous inhibition of the wakefulness-promoting neurons in the TMN, suggesting that safranal may be a hypnotic substance.

/pdf/safranal-enhances-non-rapid-eye-movement-sleep-in-30o0n09948.pdf

Safranal Enhances Non-Rapid Eye Movement Sleep in Pentobarbital-Treated Mice

After experiencing a traumatic brain injury (TBI), the majority of patients will develop sleep–wake disorders (SWD). These can include insomnia, pleiosomnia, excessive daytime sleepiness, obstructive and/or central sleep apnea, circadian sleep–wake disorders, and potentially a variety of parasomnias. Untreated SWD may impede the recovery process and can negatively impact attention, executive function, and working memory. Importantly, these patients tend to misperceive their posttraumatic sleep problems. Consequently, interviews performed in standard clinical practice will not sufficiently capture SWD patients, potentially compromising safety and productivity. In this review, the authors outline the state of current TBI-related SWD, highlighting proposed mechanisms, treatment modalities, and areas for further clinical investigation. They highlight data examining a role for slow wave sleep (SWS) in the enhancement of neural repair. They also examine the utility of enhanced cohort recruitment and SWD biomarker discovery via use of social media, smart-devices, and data-sharing networks.

TBI and Sleep-Wake Disorders: Pathophysiology, Clinical Management, and Moving towards the Future.

Purposes To explore the value of metagenomic next-generation sequencing (mNGS) in diagnosing pneumocystis jiroveciipneumonia (PJP) in the immunocompromised patients. Methods Data of 122 patients with PJP in an immunosuppressed state and 67 non-PJP patients were collected. The diagnostic efficacy of mNGS was compared with the conventional methods, including Gomori methenamine silver (GMS) staining and serum (1,3)-β-D-glucan (BDG). Changes of anti-microbial therapy for patients with PJP based on mNGS results were also reviewed. Results The diagnostic sensitivity of mNGS to PJP was higher than that of GMS and BDG (100% vs. 15 and 74.5%, p < 0.001). The diagnostic specificity (91.%) was lower than that of GMS (100%), and similar with BDG (89.6%). In addition to P. jirovecii, mNGS revealed co-pathogens like human β-herpesvirus 5, human γ-pesvirus 4, and some other opportunistic pathogens. The reads of mNGS were remarkably higher in BALF than in blood samples. Initial antimicrobial treatment was modified in 89.3% patients based on the mNGS results, and 74 cases (60.7%) were treated with anti-P. jirovecii therapy. Conclusion mNGS is highly efficient in diagnosing PJP and good at identifying pathogens in mixed infections.

/pdf/metagenomic-next-generation-sequencing-is-highly-efficient-296nvpdw.pdf

Metagenomic Next-Generation Sequencing Is Highly Efficient in Diagnosing Pneumocystis Jirovecii Pneumonia in the Immunocompromised Patients

Adenosine and Sleep-Wake Regulation: Adenosine and Sleep-Wake Regulation

Abstract The tumor microenvironment (TME) represents a milieu enabling cancer cells to develop malignant properties, while concerted interactions between cancer and stromal cells frequently shape an “activated/reprogramed” niche to accelerate pathological progression. Here we report that a soluble factor epiregulin (EREG) is produced by senescent stromal cells, which non-cell-autonomously develop the senescence-associated secretory phenotype (SASP) upon DNA damage. Genotoxicity triggers EREG expression by engaging NF-κB and C/EBP, a process supported by elevated chromatin accessibility and increased histone acetylation. Stromal EREG reprograms the expression profile of recipient neoplastic cells in a paracrine manner, causing upregulation of MARCHF4, a membrane-bound E3 ubiquitin ligase involved in malignant progression, specifically drug resistance. A combinational strategy that empowers EREG-specific targeting in treatment-damaged TME significantly promotes cancer therapeutic efficacy in preclinical trials, achieving response indices superior to those of solely targeting cancer cells. In clinical oncology, EREG is expressed in tumor stroma and handily measurable in circulating blood of cancer patients post-chemotherapy. This study establishes EREG as both a targetable SASP factor and a new noninvasive biomarker of treatment-damaged TME, thus disclosing its substantial value in translational medicine. 

/pdf/targeting-epiregulin-in-the-treatment-damaged-tumor-2e94h0i0.pdf

Targeting epiregulin in the treatment-damaged tumor microenvironment restrains therapeutic resistance

Cellular senescence is a state of stable growth arrest, usually accompanied by development of the senescence-associated secretory phenotype (SASP). Although senescent cells remain metabolically active, little is known about their metabolic landscape and in vivo pathophysiological implications. Here we show that expression of the pyruvate dehydrogenase (PDH) inhibitory enzyme, pyruvate dehydrogenase kinase 4 (PDK4), is significantly upregulated in human senescent stromal cells. Preferentially expressed upon genotoxicity-induced senescence (GIS), PDK4 is negatively correlated with posttreatment survival of cancer patients. Upon cellular senescence, PDK4 shifts glucose metabolic flux from oxidative phosphorylation to aerobic glycolysis, causing enhanced lactate production and forming an acidic microenvironment. However, distinct from the cancer cell-featured Warburg effect, senescent cells maintain an intensive use of pyruvate through the tricarboxylic acid cycle (TCA), displaying increased respiration and redox activity, indicative of a special form of metabolic reprogramming. Conditioned media from PDK4+ stromal cells change global expression and promote malignancy of recipient cancer cells in vitro and accelerate tumor progression in vivo. Pharmacologically targeting PDK4 restrains the adverse effects of PDK4 in cell-based assays, while promoting tumor regression and extending posttreatment survival in preclinical trials. Together, our study substantiates the hypercatabolic nature of senescent cells, and reveals a metabolic link between senescence-associated acidic microenvironment and age-related pathologies including but not limited to cancer.

/pdf/senescent-cells-develop-pdk4-dependent-hypercatabolism-and-3jiv77k4.pdf

Qi Xu

Papers

Metagenomic Next-Generation Sequencing Is Highly Efficient in Diagnosing Pneumocystis Jirovecii Pneumonia in the Immunocompromised Patients

Adenosine and Sleep-Wake Regulation: Adenosine and Sleep-Wake Regulation

Targeting epiregulin in the treatment-damaged tumor microenvironment restrains therapeutic resistance

Senescent cells develop PDK4-dependent hypercatabolism and form an acidic microenvironment to drive cancer resistance