A Multimodal Feature Fusion Framework for Sleep-Deprived Fatigue Detection to Prevent Accidents.

Sleep-deprived fatigued person is likely to commit more errors that may even prove to be fatal. Thus, it is necessary to recognize this fatigue. The novelty of the proposed research work for the detection of this fatigue is that it is nonintrusive and based on multimodal feature fusion. In the proposed methodology, fatigue is detected by obtaining features from four domains: visual images, thermal images, keystroke dynamics, and voice features. In the proposed methodology, the samples of a volunteer (subject) are obtained from all four domains for feature extraction, and empirical weights are assigned to the four different domains. Young, healthy volunteers (n = 60) between the age group of 20 to 30 years participated in the experimental study. Further, they abstained from the consumption of alcohol, caffeine, or other drugs impacting their sleep pattern during the study. Through this multimodal technique, appropriate weights are given to the features obtained from the four domains. The results are compared with k-nearest neighbors (kNN), support vector machines (SVM), random tree, random forest, and multilayer perceptron classifiers. The proposed nonintrusive technique has obtained an average detection accuracy of 93.33% in 3-fold cross-validation.

A Comparative Analysis of Effectiveness of Recombinant Interleukin-11 Versus Papaya Leaf Extract for Treatment of Thrombocytopenia: A Review.

Platelets or thrombocytes play an important role in thrombosis and maintaining hemostasis. Thrombocytes help in forming blood clots at the site of the wound. When the level of platelets decreases, uncontrolled bleeding occurs which can result in mortality. A decrease in the blood platelet level is known as thrombocytopenia which can be caused due to various reasons. A variety of treatment options are available for thrombocytopenia like platelet transfusion, splenectomy, platelet management with various types of corticosteroids, and recombinant interleukin-11 (rhIL-11). The use of rhIL-11 is approved by FDA for the treatment of thrombocytopenia. rhIL-11 is a recombinant cytokine that is administered to patients suffering from chemotherapy-induced thrombocytopenia as it enhances megakaryocytic proliferation which aids in platelet production. But this treatment has various side effects and is costly. Hence, there is a crucial need to identify cost-effective alternative strategies that present no side effects. The majority of the population in low-income countries requires a functional and cost-effective treatment for low thrombocyte count. Carica papaya is a tropical herbaceous plant that has been reported in recovering low platelet count during dengue virus infection. Even though multiple benefits of the Carica papaya leaf extract (CPLE) are popular, the active compound present in it, which mediates these benefits, remains to be identified. This review aims to highlight the different aspects of rhIL-11 and CPLE-induced platelet counts and their limitations and benefits in the treatment of thrombocytopenia. The literature related to the treatment of thrombocytopenia using rhIL-11 and CPLE from 1970 to 2022 was searched using PubMed and Google Scholar databases with the keywords Recombinant Interleukin-11, Papaya Leaf Extract, Thrombocytopenia, and Platelets.

Elucidating the role of hypoxia/reoxygenation in hippocampus-dependent memory impairment: do SK channels play role?

Professionals and mountaineers often face the problem of reperfusion injury due to re-oxygenation, upon their return to sea-level after sojourn at high altitude. Small conductance calcium-activated potassium channels (SK channels) have a role in regulating hippocampal synaptic plasticity. However, the role of SK channels under hypoxia-reoxygenation (H/R) is unknown. The present study hypothesized that SK channels play a significant role in H/R induced cognitive dysfunction. Sprague-Dawley rats were exposed to simulated HH (25,000 ft) continuously for 7 days followed by reoxygenation periods 3, 6, 24, 48, 72 and 120 h. It was observed that H/R exposure caused impairment in spatial memory as indicated by increased latency (p < 0.001) and pathlength (p < 0.001). The SK1 channel expression increased upon HH exposure (102.89 ± 7.055), which abrogated upon reoxygenation. HH exposure results in an increase in SK2 (CA3, 297.67 ± 6.69) and SK3 (CA1, 246 ± 5.13) channels which continued to increase gradually upon reoxygenation. The number of pyknotic cells (24 ± 2.03) (p < 0.01) and the expression of caspase-3 increased with HH exposure, which continued in the reoxygenation group (177.795 ± 1.264). Similar pattern was observed in lipid peroxidation (p < 0.001), LDH activity (p < 0.001) and ROS production (p < 0.001). A positive correlation of memory, cell death and oxidative stress indicates that H/R exposure increases oxidative stress coupled with SK channel expression, which may play a role in H/R-induced cognitive decline and neurodegeneration.

Saliva panel of protein candidates: A comprehensive study for assessing high altitude acclimatization.

Altitude acclimatization describes the processes whereby lowland humans respond to decreased partial pressure of oxygen. It refers to the changes seen as beneficial and involves a series of physiological adjustments that compensate for reduced ambient PO2, as opposed to changes that are pathological. Although numerous reports document the physiological effects of exposure to hypobaric hypoxia of varying durations but an interesting aspect overlooked by many researchers is that of acclimatization related studies. As proteome, a dynamic entity responds immediately to external stimuli, protein markers and their trends can be studied to assess acclimatization status of an individual. Compared to blood, the use of saliva is advantageous because sample collection and processing are easy, minimally invasive, low cost and better tolerated by individuals. In this study, we employed iTRAQ based LC-MS/MS technique for comparing saliva samples from humans exposed to hypobaric hypoxia from 7 to 120 days with normoxic controls followed by analysis using Ingenuity Pathway Analysis software and validation by immunoassays. Nearly 67 proteins were found to be differentially expressed in the exposed groups as compared to normoxia indicating modulated canonical pathways as lipid metabolism; acute phase response signalling and proteins as carbonic anhydrase 6, alpha-enolase, albumin, and prolactin inducible protein. Collectively, this study provides the proof of concept for the non-invasive assessment of high altitude acclimatization.

Complement activation sustains neuroinflammation and deteriorates adult neurogenesis and spatial memory impairment in rat hippocampus following sleep deprivation.

BACKGROUND: An association between neuroinflammation, reduced adult neurogenesis, and cognitive impairment has been established in sleep deprivation (SD). Complement receptors are expressed on neuronal and glial cells, thus, regulate the neuroinflammation, neurogenesis and learning/memory. However, understanding of the effect of SD on the brain-immune system interaction associated with cognitive dysfunction and its mechanisms is obscure. We hypothesized that complement activation induced changes in inflammatory and neurogenesis related proteins might be involved in the cognitive impairment during SD. METHODOLOGY: Adult male Sprague Dawley rats were used. Rats were sleep deprived for 48 h using a novel automated SD apparatus. Dosage of BrdU (50 mg/kg/day, i.p. in 0.07 N NaOH), complement C3a receptor antagonist (C3aRA; SB290157; 1 mg/kg/day, i.p.) in 1.16% v/v PBS and complement C5a receptor antagonist (C5aRA; W-54011; 1 mg/kg/day, i.p.) in normal saline were used. Rats were subjected to spatial memory evaluation following SD. Hippocampal tissue was collected for biochemical, molecular, and immunohistochemical studies. T-test and ANOVA were used for the statistical analysis. RESULTS: An up-regulation in the levels of complement components (C3, C5, C3a, C5a) and receptors (C3aR and C5aR) in hippocampus, displayed the complement activation during SD. Selective antagonism of C3aR/C5aR improved the spatial memory performance of sleep-deprived rats. C3aR antagonist (C3aRA) or C5aR antagonist (C5aRA) treatment inhibited the gliosis, maintained inflammatory cytokines balance in hippocampus during SD. Complement C3aR/C5aR antagonism improved hippocampal adult neurogenesis via up-regulating the BDNF level following SD. Administration of C3aRA and C5aRA significantly maintained synaptic homeostasis in hippocampus after SD. Gene expression analysis showed down-regulation in the mRNA levels of signal transduction pathways (Notch and Wnt), differentiation and axogenous proteins, which were found to be improved after C3aRA/C5aRA treatment. These findings were validated at protein and cellular level. Changes in the corticosterone level and ATP-adenosine-NO pathway were established as the key mechanisms underlying complement activation mediated consequences of SD. CONCLUSION: Our study suggests complement (C3a-C3aR and C5a-C5aR) activation as the novel mechanism underlying spatial memory impairment via promoting neuroinflammation and adult neurogenesis decline in hippocampus during SD, thereby, complement (C3aR/C5aR) antagonist may serve as the novel therapeutics to improve the SD mediated consequences.

Impact of high altitude on key determinants of female reproductive health: a review.

Imperishable research work was done on females visiting high-altitude (HA) areas for recreational activities or job purposes as well as on female HA natives. Hypoxia at HA is an unavoidable condition that affects the determinants of female reproductive functions like, the age of menarche and menopause, whole reproductive span, hormone synthesis, and fertility. This review will emphasize whether HA hypoxia is a threat to women: residents or visitors by analyzing these proximate determinants. Delayed menarcheal and advanced menopausal age was found to shorten the reproductive span in some HA populations, whereas in some cases, menstrual cycle was also reported to be irregular. In addition, the completed fertility rate (CFR) was increased when people migrated to lower altitude. Altered stress hormones and reproductive hormones were observed in sea-level females exposed to HA. Oxidative stress (OS) at HA was also reviewed to explain the probable reasons for the observed changes in these determinants because disturbed redox homeostasis may be a connecting link, affecting the reproductive functions. In conclusion, HA hypoxia plays a crucial role on various determinants of female reproductive health and this review will be helpful for more precise study along with the probable underlying mechanisms responsible for the changes in female reproductive functions at HA.

Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation.

BACKGROUND: Sleep deprivation (SD) leads to cognitive impairment. Neuroinflammation could be a significant contributing factor in the same. An increase in regional brain pro-inflammatory cytokines induces cognitive deficits, however, the magnitude of the effect under SD is not apparent. It is plausible that microglia activation could be involved in the SD-induced cognitive impairment by modulation of neuronal cell proliferation, differentiation, and brain-derived neuronal factor (BDNF) level. The present study aimed to evaluate the possible beneficial effect of minocycline in amelioration of spatial memory decline during SD by its anti-inflammatory and neuroprotective actions. We scrutinized the effect of minocycline on the inflammatory cytokine levels associated with glial cells (microglia and astrocytes) activity and neurogenesis markers crucial for behavioral functions during SD. METHODS: Male Sprague-Dawley rats weighing 230-250 g were sleep deprived for 48 h using automated cage shaking apparatus. The spatial memory was tested using MWM apparatus immediately after completion of SD with and without minocycline. The animals were euthanized, blood was collected, and brain was extracted for neuroinflammation and neurogenesis studies. The set of experiments were also conducted with use of temozolomide, a neurogenesis blocker. RESULTS: Minocycline treatment increased the body weight, food intake, and spatial memory performance which declined during SD. It reduced the pro-inflammatory and increased the anti-inflammatory cytokine levels in hippocampus and plasma and inhibited the reactive gliosis in the hippocampus evidenced by improved cell count, morphology, and immunoreactivity. Additionally, minocycline administration promoted neurogenesis at different stages: proliferation (BrdU, Ki-67), differentiation (DCX) cells and growth factor (BDNF). However, no significant change was observed in maturation (NeuN) during SD. In addition, molecules related to behavior, inflammation, and neurogenesis were shown to be more affected after temozolomide administration during SD, and changes were restored with minocycline treatment. We observed a significant correlation of neurogenesis with microglial activation, cytokine levels, and spatial memory during SD. CONCLUSION: The present study demonstrated that the SD-induced decline in spatial memory, neuronal cells proliferation, differentiation, and BDNF level could be attributed to upregulation of neuroinflammatory molecules, and minocycline may be an effective intervention to counteract these changes. Microglial activation is involved in SD-induced changes in inflammatory molecules, neurogenesis, and spatial memory.

Tyrosine ameliorates heat induced delay in event related potential P300 and contingent negative variation.

The efficacy of tyrosine, a catecholamine precursor, as a countermeasure in the reduction of cognitive decline during heat exposure (HE) using event-related potential P300, and contingent negative variation (CNV) was evaluated. Ten healthy males, age 20-30years participated in the study. Volunteers received placebo or tyrosine (6.5g) 90min prior to HE (1.5h in 45°C+30% RH). P300 latency was significantly increased (p<0.01) during exposure with placebo, which was reduced significantly (p<0.01) after tyrosine supplementation. There was an increase in CNV M100 latency (p<0.05) and reaction time (p<0.01) and decrease in M100 amplitude (p<0.01) during HE with placebo, which returns to near normal level with the tyrosine administration. A significantly higher plasma norepinephrine (p<0.05), dopamine and epinephrine levels were detected in tyrosine supplemented group post heat exposure. HE increases the brain catecholamine activity thereby reduces the plasma norepinephrine and dopamine level leading to a reduction in cognitive performances. Tyrosine supplementation increases the catecholamine level and reduces the impairment of cognitive performance during HE.

The effect of non-pharmacological interventions on sleep quality in people with sleep disturbances: A systematic review and a meta-analysis.

Sleep is the elixir of life. Both healthy populations and patients with chronic diseases experience sleep disturbances in their lifetime. Pharmacological agents to induce sleep in individuals with sleep disturbances pose side effects like tolerance and dependence, warranting the development of alternative non-pharmacological interventions with less or no adverse effects. However, deciphering comprehensive evidence on the translational potential of these alternative therapies remains difficult. In the current paper, we systematically reviewed the recent literature on the effect of non-pharmacological interventions (NPIs) on improving sleep quality in both healthy and diseased populations experiencing sleep disturbances. We searched PubMed, Science Direct, Cochrane Controlled Trials, and Web of Science databases from inception to June 2022 for randomized controlled trials and cohort studies evaluating the sleep quality of individuals. We performed a meta-analysis using the random effects model with Pittsburgh Sleep Quality Index (PSQI) as an outcome measure to evaluate the effect of five distinct NPIs on sleep quality in normal and people with different medical conditions. Subgroup analyses and sensitivity analyses were done for heterogeneity analysis and to check the consistency of results, respectively. In 16 trials reporting on 1885 subjects, that all NPIs like Resistance Training (SMD -0.29, 95% CI -0.64 to 0.05; p = 0.09); Yoga (SMD -0.48, 95% CI -0.72 to -0.25; p < 0.0001); Cognitive Behavioral Therapy (SMD -1.69, 95% CI -2.70 to -0.68; p = 0.001); Music (SMD -1.42, 95% CI -1.99 to -0.85; p < 0.00001); Light (SMD -0.43, 95% CI -0.77 to -0.09; p = 0.01) have substantially decreased the global PSQI scores. The findings of the randomized studies and a cohort study included in qualitative synthesis demonstrated that the global PSQI scores improved significantly as compared to the placebo groups. Despite the limitations of clinical heterogeneity in subjects, our results demonstrate a positive impact of the studied NPIs on sleep quality in individuals experiencing sleep disturbances. However, comprehensive double-blinded controlled trials are indispensable in the future, emphasizing the objective sleep quality and inter-individual differences in response to the intervention.

Meditation as an intervention for cognitive disturbances following total sleep deprivation.

BACKGROUND & OBJECTIVES: Decline in cognitive functions is a major challenge for professionals during sustained wakefulness. We used middle latency response (MLR), event related potentials P300-ERP and contingent negative variation (CNV) and Raven's Advanced Progressive Matrices (RAPM) - a standard neuropsychological test were used to evaluate cognitive impairment after total sleep deprivation (SD); and to study the impact of meditation as an intervention for this impairment. METHODS: Healthy male volunteers (n=10) drawn randomly from the Indian Army participated in a 6-night study design executed before and after two months of meditation practice: night 1-adaptation, night 2-baseline, night 3-24 h SD, night 4-recovery sleep, night 5-24 h SD after 60 days meditation, night 6-recovery sleep after SD. A 36 h SD was obtained by keeping the subject awake for 12 h after 24 h SD. RESULTS: The latency and amplitude of P300 increased after 36 h SD. Amplitudes and latencies of both early and late CNV increased after 24 and 36 h SD, indicating deficient orientation and impairment of attention and perception. Prolonged CNV reaction time after 36 h SD manifested deficient motor response following second (imperative) stimulus. Latency of MLR Na registered significant change following 36 h SD compared to baseline (P<0.01) and recovery (P<0.05). RAPM score showed significant decrease after 36 h of wakefulness indicating impaired analytical ability and difficulty in problem solving. None of these parameters showed any significant alteration after SD, following meditation practice. INTERPRETATION & CONCLUSIONS: The present results showed that SD impaired cognitive performance to graded extents significantly, but this deterioration could be improved to a significant extent using meditation.

Sleep architecture at 4300 m altitude in a sample of Indian lowlanders.

The present study aimed to evaluate sleep architecture at 4300 m in a sample of 10 healthy Indian lowlanders, mean age 25.7 +/- 5.1 yrs. Polysomnography on two consecutive nights each was performed at sea level and 4300 m, the first night for adaptation and the second one for actual recording. Total sleep time reduced from 433.33 +/- 8.95 to 412.06 +/- 13.13 minutes (P < 0.0005), sleep latency increased from 11.56 +/- 6.85 to 22.22 +/- 7.95 minutes (P < 0.0025), deep NREM sleep (S3 + S4) reduced from 79.56 +/- 28.45 to 45.39 +/- 25.32 minutes (P < 0.01), light NREM sleep (S1 + S2) increased from 272.94 +/- 20.63 to 296.72 +/-23.24 minutes (P < 0.05), REM decreased from 80.89 +/- 7.65 to 69.94 +/- 11.30 minutes (P < 0.02) and periodic breathing was present in 4 of 10 participants on the second night at 4300 m. Decreased sleep quality (P < 0.0005) and increased sleep disturbances (P < 0.0005) were reported in subjective ratings at high altitude. Changes in sleep architecture similar to but of a greater magnitude are present on the second night of staged induction to 4300 m, than reported at 3500 m in our earlier study.

Hypobaric Hypoxia Induces Deficits in Adult Neurogenesis and Social Interaction via Cyclooxygenase-1/ EP1 Receptor Pathway Activating NLRP3 Inflammasome.

Low oxygen environments, like hypobaric hypoxia (HH), are common nodes in a number of diseases characterized by neuroinflammation, which is detrimental to the structural and functional aspects of hippocampal circuitry. Hypoxic conditions lead to elevation of inflammasome-mediated inflammation that may contribute to cognitive deficits. However, a systematic investigation of the impact of inflammasome-mediated neuroinflammation on the components of neurogenic niche during HH remains to be elusive. Cerebral hypoxia was induced in adult male Sprague Dawley rats via decreasing partial pressure of oxygen. The effect of HH (1, 3, and 7 days at 25,000 ft) on social memory, anxiety, adult neurogenesis, and NLRP3- (NLR family pyrin domain containing 3) mediated neuroinflammation in the dentate gyrus (DG) was explored in detail. Furthermore, we explored the therapeutic efficacy of cyclooxygenase-1 inhibitor (valeryl salicylate, 5 mg/kg/day, i.p.) and EP1 receptor (EP1R) antagonist (SC19220, 1 mg/kg/day, i.p.) on HH-induced deficits. Seven days of HH exposure induced alteration in social and anxiety-like behavior along with perturbation in adult neurogenesis. Elevation in NLRP3, caspase-1, and IL-1ß levels was observed during HH from day 1. A notable increase in the COX-1/EP1R pathway in activated glial cells in DG was evident during HH. COX-1 inhibitor and EP1R antagonist mitigated the detrimental effects of HH on social memory, adult neurogenesis via blunting NLRP3-mediated inflammation. Our data showed induction of the COX-1/EP1R pathway in the glial cells, which is detrimental to neurogenesis and social memory, opening up the possibility that the COX-1/EP1R pathway is a plausible target for inflammasome-related neurogenesis impairments.

Event related potential (ERP) P300 after 6 months residence at 4115 meter.

BACKGROUND & OBJECTIVES: The P300 wave is an event related potential (ERP) elicited by infrequent, task-relevant stimuli and appeared at about 300 ms, represents higher cognitive function of information processing, working memory or stimulus categorization. Hypobaric hypoxia deteriorates the cognitive function during the short term stay (days to few weeks) at high altitude. The present study was carried out to evaluate the P300 responses during long duration stay (1 month and 6 months) at high altitude (HA, 4115 m) in a sample of Indian lowlanders. METHODS: The study was carried out on 18 healthy male volunteers at sea level (SL). The volunteers were stage inducted to 4115 m altitude in the Eastern Himalayas. The P300 was recorded after 1 and 6 months of their stay at HA. RESULTS: The latencies of peaks N100, P200 and N200 waves did not show any significant changes after 1 and 6 months of stay at HA as compared to SL. The P300 latency was significantly delayed after 1 month and further delayed after 6 month of residence at 4115 m. The P200 and P300 amplitudes did not show any changes. INTERPRETATION & CONCLUSIONS: The increase in P300 latency indicated that long duration of stay at high altitude slows the stimulus evaluation processes. The observations suggest that hypoxia causes slowing of the signal processing at HA. The magnitude of the effects of hypobaric hypoxia may be dependent upon the duration of residence at high altitude.

Sleep, Cognition, and Yoga.

Stress is one of the major problems globally, associated with poor sleep quality and cognitive dysfunction. Modern society is plagued by sleep disturbances, either due to professional demands or lifestyle or both the aspects, often leading to reduced alertness and compromised mental function, besides the well documented ill effects of disturbed sleep on physiological functions. This pertinent issue needs to be addressed. Yoga is an ancient Indian science, philosophy and way of life. Recently, yoga practice has become increasingly popular worldwide. Yoga practice is an adjunct effective for stress, sleep and associated disorders. There are limited well controlled published studies conducted in this area. We reviewed the available literature including the effect of modern lifestyle in children, adolescents, adults and geriatric population. The role of yoga and meditation in optimizing sleep architecture and cognitive functions leading to optimal brain functioning in normal and diseased state is discussed. We included articles published in English with no fixed time duration for literature search. Literature was searched mainly by using PubMed and Science Direct search engines and critically examined. Studies have revealed positive effects of yoga on sleep and cognitive skills among healthy adults as well as patients of some neurological diseases. Further, on evaluating the published studies, it is concluded that sleep and cognitive functions are optimized by yoga practice, which brings about changes in autonomic function, structural changes, changes in metabolism, neurochemistry and improved functional brain network connectivity in key regions of the brain.

Anti-Mullerian Hormone and Macrophage Migration Inhibitory Factor Determine the Reproductive Health of Ladakhi Women Residing at 3,500 m.

Shaw, Snigdha, Himashree Gidugu, Gopinath Bhaumik, Maramreddy Prasanna Kumar Reddy, Usha Panjwani, and Dishari Ghosh. Anti-Mullerian hormone and macrophage migration inhibitory factor determine the reproductive health of Ladakhi women residing at 3,500 m. High Alt Med Biol. 22:317-326, 2021. Background: Reproductive health of Ladakhi high-altitude (HA) native females was investigated for the first time in this study. Available literature suggest that, female reproductive cycle and hormonal profile varies in different HA populations due to heterogeneity. Although these studies illustrate some progress on the role of HA hypoxia, it still leaves scope for evaluation of the remaining mechanisms involved in the maintenance of reproductive health in this contemporary population. Materials and Methods: Menstrual details, phasic variations in circulatory steroid hormones, and gonadotropins along with oxytocin in sea level (SL) and HA (∼3,500 m) native females of India were assessed. Moreover, ovarian reserve marker anti-Mullerian hormone (AMH) and proinflammatory cytokine macrophage migration inhibitory factor (MIF) were measured. Results: A difference in Ladakhi women was registered compared to SL, regarding luteinizing hormone (LH) (2.6 mIU/ml vs. 4.4 mIU/ml, p < 0.05) and progesterone (P) (4.1 ng/ml vs. 9.4 ng/ml, p < 0.05) levels in their luteal phase. Reduced LH might contribute to poor development of the ovarian corpus luteum, subsequently diminish P level. Decreased AMH level in three age groups: 21-30 years (1.4 ng/ml vs. 3.2 ng/ml, p < 0.01), 31-40 years (0.6 ng/ml vs. 2.1 ng/ml, p < 0.01), and >40 years (0.4 ng/ml vs. 1.7 ng/ml, p < 0.01) of Ladakhi women were recorded than their SL counterpart. Elevated oxytocin (83.5 ng/ml vs. 76.3 ng/ml, p < 0.05) and MIF levels (70.2 ng/ml vs. 49.7 ng/ml, p < 0.01) along with low P and AMH levels delineated the reason for recorded early menopause (43.9 years), shorter reproductive span (∼29 years), and history of miscarriage in HA dwellers compared to SL. Conclusion: Therefore, the findings insinuated that the response of the reproductive system to hypoxia in Ladakhi women differs from SL women, and the adaptive response in these women might be in favor of their reproductive health.

TMT-Based Plasma Proteomics Reveals Dyslipidemia Among Lowlanders During Prolonged Stay at High Altitudes.

Acute exposure to high altitude perturbs physiological parameters and induces an array of molecular changes in healthy lowlanders. However, activation of compensatory mechanisms and biological processes facilitates high altitude acclimatization. A large number of lowlanders stay at high altitude regions from weeks to months for work and professional commitments, and thus are vulnerable to altitude-associated disorders. Despite this, there is a scarcity of information for molecular changes associated with long-term stay at high altitudes. In the present study, we evaluated oxygen saturation (SpO2), heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) of lowlanders after short- (7 days, HA-D7) and long-term (3 months, HA-D150) stay at high altitudes, and used TMT-based proteomics studies to decipher plasma proteome alterations. We observed improvements in SpO2 levels after prolonged stay, while HR, SBP, and DBP remained elevated as compared with short-term stay. Plasma proteomics studies revealed higher levels of apolipoproteins APOB, APOCI, APOCIII, APOE, and APOL, and carbonic anhydrases (CA1 and CA2) during hypoxia exposure. Biological network analysis also identified profound alterations in lipoprotein-associated pathways like plasma lipoprotein assembly, VLDL clearance, chylomicron assembly, chylomicron remodeling, plasma lipoprotein clearance, and chylomicron clearance. In corroboration, lipid profiling revealed higher levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL) for HA-D150 whereas high density lipoproteins (HDL) levels were lower as compared with HA-D7 and sea-level indicating dyslipidemia. We also observed higher levels of proinflammatory cytokines IL-6, TNFα, and CRP for HA-D150 along with oxidized LDL (oxLDL), suggesting vascular inflammation and proartherogenic propensity. These results demonstrate that long-term stay at high altitudes exacerbates dyslipidemia and associated disorders.

Electrophysiological correlates of cognition improve with nap during sleep deprivation.

The efficacy of a 30-min nap as a countermeasure in the reduction of cognitive decline following 24 h of sleep deprivation (SD) on subjective sleepiness scales, event-related potential (ERP) P300, and contingent negative variation (CNV) was evaluated. The experiment was performed in three sessions on different days between 7 and 8 a.m. on nine normal, healthy males, of age 25-30 years: Session 1. Baseline recordings; Session 2, after one night's total sleep deprivation, and; Session 3, after 1 week of Session 1, following one night's sleep deprivation along with a 30-min nap opportunity between 1.00 and 3.00 a.m. Subjective sleepiness scores increased after SD as compared to baseline, but reduced significantly after nap (P < 0.05). There was an increase in P3 peak latency of ERP following SD (16%, P < 0.01), which was reduced with nap (10.7%, P < 0.05).There was an increase in CNV M1 peak latency after SD (18%) which decreased with the use of nap (12.5%) (P < 0.01). The CNV reaction time increased following SD (39.3%) and decreased with the use of nap (24%) (P < 0.01). No significant effects on ERP N1, P1, N2 latencies, P2 and P3 amplitudes and CNV N1, P3, M2 peak latencies and M1, and M2 amplitudes were observed. It was concluded that a 30-min nap, between 1.00 and 3.00 a.m. during night SD, reduces the cognitive decline following 24 h of SD in terms of its electro-physiological correlates. The study is of applied value in optimization of cognitive performance in professions demanding night work schedules.

Fear memory is impaired in hypobaric hypoxia: Role of synaptic plasticity and neuro-modulators in limbic region.

AIMS: Evidence suggests that hypobaric hypoxia (HH) exposure causes biochemical and molecular level perturbations in brain resulting in associated cognitive dysfunction. However, the possible effect of HH on amygdala and the associated limbic regions based functions remains elusive. Regulated fear expression is essential for quick adaptations and optimal behavioral response. Therefore, the present study aims to investigate the effect of HH on biochemical and molecular mechanisms in amygdala involved in fear memory regulation along with the hippocampus and prefrontal cortex based fear memory. MATERIALS AND METHODS: Adult male Sprague Dawley rats were subjected to cued and contextual fear memory assessment following simulated HH exposure (25,000 ft) for 3 and 7 days. Plasma and limbic tissue (Prefrontal cortex, hippocampus and amygdala) samples were collected for biochemical and molecular studies. KEY FINDINGS: Results revealed a decrease in contextual and cued fear memory retrieval, indicating fear memory dysregulation under HH exposure. Increased level of norepinephrine, dopamine, corticosterone and glutamate along with a decline in serotonin and GABA level was observed in plasma and limbic tissue after 3 and 7 days of HH exposure. Dysregulation of neuromodulation, neuronal survival and synaptic homeostasis was also evident from observed decline in tryptophan hydroxylase, BDNF, synaptophysin, synapsin1, PSD95 and an increase in tyrosine hydroxylase immunoreactivity in limbic region under HH exposure. SIGNIFICANCE: Dysregulation of limbic region signaling molecules associated with survival and maintenance of synaptic plasticity (Synaptophysin, synapsin1 and PSD95), neurotrophic factor (BDNF) and shift in monoamines, corticosterone, glutamate and GABA levels may contribute to the HH induced fear memory impairment.

Hypobaric hypoxia induced fear and extinction memory impairment and effect of Ginkgo biloba in its amelioration: Behavioral, neurochemical and molecular correlates.

Regulated fear and extinction memory is essential for balanced behavioral response. Limbic brain regions are susceptible to hypobaric hypoxia (HH) and are putative target for fear extinction deficit and dysregulation. The present study aimed to examine the effect of HH and Ginkgo biloba extract (GBE) on fear and extinction memory with the underlying mechanism. Adult male Sprague-Dawley rats were evaluated for fear extinction and anxious behavior following GBE administration during HH exposure. Blood and tissue (PFC, hippocampus and amygdala) samples were collected for biochemical, morphological and molecular studies. Results revealed deficit in contextual and cued fear extinction following 3 days of HH exposure. Increased corticosterone, glutamate with decreased GABA level was found with marked pyknosis, decrease in apical dendritic length and number of functional spines. Decline in mRNA expression level of synaptic plasticity genes and immunoreactivity of BDNF, synaptophysin, PSD95, spinophilin was observed following HH exposure. GBE administration during HH exposure improved fear and extinction memory along with decline in anxious behavior. It restored corticosterone, glutamate and GABA levels with an increase in apical dendritic length and number of functional spines with a reduction in pyknosis. It also improved mRNA expression level and immunoreactivity of neurotrophic and synaptic proteins. The present study is the first which demonstrates fear extinction deficit and anxious behavior following HH exposure. GBE administration ameliorated fear and extinction memory dysregulation by restoration of neurotransmitter levels, neuronal pyknosis and synaptic connections along with improved neurotrophic and synaptic protein expressions.