Recent advancements and prospects in noble and non-noble electrocatalysts for materials methanol oxidation reactions.

The direct methanol fuel cell (DMFC) represents a highly promising alternative power source for small electronics and automobiles due to its low operating temperatures, high efficiency, and energy density. The methanol oxidation process (MOR) constitutes a fundamental chemical reaction occurring at the positive electrode of a DMFC. Pt-based materials serve as widely utilized MOR electrocatalysts in DMFCs. Nevertheless, various challenges, such as sluggish reaction rates, high production costs primarily attributed to the expensive Pt-based catalyst, and the adverse effects of CO poisoning on the Pt catalysts, hinder the commercialization of DMFCs. Consequently, endeavors to identify an alternative catalyst to Pt-based catalysts that mitigate these drawbacks represent a critical focal point of DMFC research. In pursuit of this objective, researchers have developed diverse classes of MOR electrocatalysts, encompassing those derived from noble and non-noble metals. This review paper delves into the fundamental concept of MOR and its operational mechanisms, as well as the latest advancements in electrocatalysts derived from noble and non-noble metals, such as single-atom and molecule catalysts. Moreover, a comprehensive analysis of the constraints and prospects of MOR electrocatalysts, encompassing those based on noble metals and those based on non-noble metals, has been undertaken.

Co-pyrolysis of plastic waste and eucalyptus waste wood for fuel pellets production: A study of fuel, mechanical, and combustion characteristics under varying binder proportion.

The study explores the effect of varying molasses proportions as a binder on the characteristics of densified char obtained through the slow co-pyrolysis of plastic waste and Eucalyptus wood waste (Waste low-density polyethylene - Eucalyptus wood (WLDPE-EW) and Waste Polystyrene - Eucalyptus wood (WPS-EW)). Pyrolysis was conducted at 500 °C with a residence time of 120 min, employing plastic to wood waste ratios of 1:2 and 1:3 (w/w). The focus was on how varying the proportion of molasses (10-30 %), influences the physical and combustion properties of the resulting biofuel pellets. Our findings reveal that the calorific value of the pellets decreased from 28.94 to 27.44 MJ/Kg as the molasses content increased. However, this decrease in calorific value was compensated by an increase in pellet mass density, which led to a higher energy density overall. This phenomenon was attributed to the formation of solid bridges between particles, facilitated by molasses, effectively decreasing particle spacing. The structural integrity of the pellets, as measured by the impact resistance index, improved significantly (43-47 %) with the addition of molasses. However, a significant change in the combustion characteristics depicted by lower ignition and burnout temperatures were observed due to decrease in fixed carbon value and increase in volatile matter content, as the proportion of molasses increased. Despite these changes, the pellets demonstrated a stable combustion profile, suggesting that molasses are an effective binder for producing biofuel pellets through the densification of char derived from the co-pyrolysis of plastic and Eucalyptus wood waste. The optimized molasses concentration analyzed through multifactor regression analysis was 16.96 % with 28 % WLDPE proportion to produce WLDPE-EW char pellets. This study highlights the potential of using molasses as a sustainable binder to enhance the mechanical and combustion properties of biofuel pellets, offering a viable pathway for the valorization of waste materials.

A Rare Case of Biloma after Ascending Cholangitis and Endoscopic Retrograde Cholangiopancreatography.

Introduction: Biloma is an uncommon form of liver abscess composed of bile usually associated with procedures of the biliary tree and gallbladder. Cholangitis can be acute or chronic, can result in partial or complete obstruction of the flow of bile. The infection of the bile is so common, that positive blood cultures are highly characteristic. In the case of a suppurative cholangitis with signs of sepsis treatment alone with antibiotics is usually not sufficient to achieve medical remission. Multiple hepatic abscesses are often present, and the mortality approaches 100% unless prompt endoscopic or surgical relief of the obstruction and drainage of infected bile are carried out. Endoscopic retrograde cholangiopancreatography ERCP with endoscopic sphincterotomy is the preferred initial procedure for both establishing a definitive diagnosis and providing effective therapy. Case description: We present the case of a 69-year-old female patient with complex chronic comorbidities who presented with acute cholangitis initially managed with endoscopically inserted stent and later complicated by sepsis and biloma formation. The bile was drained, and it showed an infection with Candida spp. requiring antifungal therapy. Conclusions: The failure to perform sphincterotomy in patients with suppurative cholangitis can contribute to the backflow of bile and worse outcomes. LEARNING POINTS: Biloma formation is a rare complication of biliary duct procedures and diseases such as cholangitis. A prompt identification of signs of complications in patients with disease of the biliary ducts is key in preventing clinical deterioration.Sphincterotomy is vital in the management of ascending cholangitis, as it prevents backflow of bile into the intrahepatic biliary system.The presence of multiple comorbidities in complex cases can become an obstacle to optimal management and drainage of septic bile.

Bioinformatic meta-analysis reveals novel differentially expressed genes and pathways in sarcoidosis.

Introduction: Sarcoidosis is a multi-system inflammatory disease of unknown origin with heterogeneous clinical manifestations varying from a single organ non-caseating granuloma site to chronic systemic inflammation and fibrosis. Gene expression studies have suggested several genes and pathways implicated in the pathogenesis of sarcoidosis, however, due to differences in study design and variable statistical approaches, results were frequently not reproducible or concordant. Therefore, meta-analysis of sarcoidosis gene-expression datasets is of great importance to robustly establish differentially expressed genes and signalling pathways. Methods: We performed meta-analysis on 22 published gene-expression studies on sarcoidosis. Datasets were analysed systematically using same statistical cut-offs. Differentially expressed genes were identified by pooling of p-values using Edgington's method and analysed for pathways using Ingenuity Pathway Analysis software. Results: A consistent and significant signature of novel and well-known genes was identified, those collectively implicated both type I and type II interferon mediated signalling pathways in sarcoidosis. In silico functional analysis showed consistent downregulation of eukaryotic initiation factor 2 signalling, whereas cytokines like interferons and transcription factor STAT1 were upregulated. Furthermore, we analysed affected tissues to detect differentially expressed genes likely to be involved in granuloma biology. This revealed that matrix metallopeptidase 12 was exclusively upregulated in affected tissues, suggesting a crucial role in disease pathogenesis. Discussion: Our analysis provides a concise gene signature in sarcoidosis and expands our knowledge about the pathogenesis. Our results are of importance to improve current diagnostic approaches and monitoring strategies as well as in the development of targeted therapeutics.

Bioplastic packaging in circular economy: A systems-based policy approach for multi-sectoral challenges.

Bioplastics have long been publicized as a sustainable plastic packaging alternative; however, their widespread industrialization is still embryonic due to complex challenges spanning multiple sectors. This review critically analyses the bioplastic lifecycle and provides a holistic evaluation of both the opportunities and potential trade-offs along their value chain. Their lifecycle is divided into three sectors: 1) resources, extraction, and manufacturing, 2) product consumption which discusses availability, consumer perception, and marketing strategies, and 3) end-of-life (EoL) management which includes segregation, recycling, and disposal. In the production phase, the primary challenges include selection of suitable raw feedstocks and addressing the techno-economic constraints of manufacturing processes. To tackle these challenges, it is recommended to source sustainable feedstocks from innovative, renewable, and waste materials, adopt green synthesis mechanisms, and optimize processes for improved efficiency. The consumption phase encompasses challenges related to market availability, cost competitiveness, and consumer perception of bioplastics. Localizing feedstock sourcing and production, leveraging the economics of scale, and promoting market demand for recycled bioplastics can positively influence the market dynamics. Additionally, dispelling misconceptions about degradability through proper labeling, and employing innovative marketing strategies to enhance consumer perception of the mechanical performance and quality of bioplastics is crucial. During the EoL management phase, major challenges include inadequate awareness, inefficient segregation protocols, and bioplastics with diverse properties that are incompatible with existing waste management infrastructure. Implementing a standardized labeling system with clear representation of suitable EoL techniques and integrating sensors and machine learning-based sorting technologies will improve segregation efficiency. Further, establishing interconnected recycling streams that clearly define the EoL pathways for different bioplastics is essential to ensure circular waste management systems. Finally, designing a comprehensive systems-based policy framework that incorporates technical, economic, environmental, and social drivers is recommended to promote bioplastics as a viable circular packaging solution.

Effects of the Affordable Care Act Medicaid Expansions on the Employment and Work Hours of Nursing Assistants in Hospitals and Nursing Homes.

We examine the effects of the Affordable Care Act Medicaid expansions on the employment and work hours of nursing assistants (NAs). We use the 2011-2019 American Community Survey data to identify NAs likely to be affected by Medicaid expansions (income up to 138% of the federal poverty level) in nursing homes and hospitals. Using classical difference-in-differences regressions, we find that Medicaid expansions have little effect on employment and work hours among NAs in the full sample. However, there is a 4.4 percentage-point increase in the probability of working part-time (<30 hours/week) for nursing home NAs (p < .05). We found no employment effects of Medicaid expansions for hospital NAs. Our study adds to the literature on the heterogeneous effects of Medicaid expansions on work effort across occupations and workplaces. The rise in part-time employment for nursing home NAs following Medicaid expansions suggests the need for improved benefits to encourage full-time employment.

ACO Clinicians Have Higher Medicare Part B Medical Services Payments Than MIPS Clinicians Under the Quality Payment Program.

The Quality Payment Program (QPP) is a Medicare value-based payment program with 2 tracks: -Advanced Alternative Payment Models (A-APMs), including two-sided risk Accountable Care Organizations (ACOs), and Merit-based Incentive Payment System (MIPS). In 2020, A-APM eligible ACO clinicians received an additional 5% positive, and MIPS clinicians received up to 5% negative or 2% positive performance-based adjustments to their Medicare Part B medical services payments. It is unclear whether the different payment adjustments have differential impacts on total medical services payments for ACO and MIPS participants. We compare Medicare Part B medical services payments received by primary care clinicians participating in ACO and MIPS programs using Medicare Provider Utilization and Payment Public Use Files from 2014 to 2018 using difference-in-differences regressions. We have 254 395 observations from 50 879 unique clinicians (ACO = 37.86%; MIPS = 62.14%). Regression results suggest that ACO clinicians have significantly higher Medicare Part B medical services payments ($1003.88; 95% CI: [579.08, 1428.69]) when compared to MIPS clinicians. Our findings suggest that ACO clinicians had a greater increase in medical services payments when compared to MIPS clinicians following QPP participation. Increased payments for Medicare Part B medical services among ACO clinicians may be driven partly by higher payment adjustment rates for ACO clinicians for Part B medical services. However, increased Part B medical services payments could also reflect clinicians switching to increased outpatient services to prevent potentially costly inpatient services. Policymakers should examine both aspects when evaluating QPP effectiveness.

Occupational Injuries in the US Nursing Homes.

BACKGROUND: Workplace injuries adversely affect worker well-being and may worsen staffing shortages and turnover in nursing homes. A better understanding of the trends in injuries in nursing homes including organizational factors associated with injuries can help improve our efforts in addressing worker injuries. OBJECTIVE: To summarize the trends in injuries and organizational correlates of injuries in US nursing homes. RESEARCH DESIGN: We combine national injury tracking data from the Occupational Safety and Health Administration (2016-2019) with nursing home characteristics from Nursing Home Compare. Our outcomes include the proportion of nursing homes reporting any injuries, the mean number of injuries, and the mean number of injuries or illnesses with days away from work, or job transfer or restriction, or both (DART). We descriptively summarize trends in injuries over time. We also estimate the association between nursing home characteristics and injuries using multivariable regressions. RESULTS: We find that approximately 93% of nursing homes reported at least 1 occupational injury in any given year. Injuries had a substantial impact on productivity with 4.1 DART injuries per 100 full-time employees in 2019. Higher bed size, occupancy, RN staffing, and chain ownership are associated with increased DART rates whereas higher overall nursing home star ratings and for-profit status are associated with decreased DART rates. CONCLUSIONS: A high proportion of nursing homes report occupational injuries that can affect staff well-being, productivity, and quality of care. Injury prevention policies should target the types of injuries occurring in nursing homes and OSHA should monitor nursing homes reporting high and repeated injuries.

Preference of trees for nest building by critically endangered white-rumped vultures (Gyps bengalensis) in Nepal.

White-rumped vultures (Gyps bengalensis) are critically endangered species, and protecting their habitats, particularly the nesting trees, may have a positive impact on their reproductive success. For a better understanding of vultures' habitat needs, the characteristics of nesting trees should be accounted. In this paper, we compare the characteristics of the trees that have vultures' nests and that do not by randomly select a control tree within a 10 m radius of the nesting tree. We extensively searched and monitored the white-rumped vultures' nests, nesting trees, and nesting tree species in Nepal between 2002 and 2022, and measured the characteristics of sampled trees such as their height, girth, canopy spread, branching orders, and whorls. We recorded 1161 nests of white-rumped vulture in total on 194 trees belonging to 19 species over the past two decades. White-rumped vultures preferred the kapok trees (Bombax ceiba) for nest construction than other tree species (χ 2 = 115.38, df = 1, p < .001) as 66.49% of nests were built on them. In the logistic regression model, the number of whorls on a tree, canopy spread, and the height of the first branch determined whether a nest was present or absent on a tree. These results help to prioritize the tree attributes in a habitat conservation plan for vultures.

Factors influencing Chinese pangolin (Manis pentadactyla) burrow selection in the Chandragiri-Champadevi hills of Kathmandu Valley, Nepal.

The Chinese pangolin (Manis pentadactyla) confronts challenges from illegal hunting, trading, and habitat degradation. Therefore, it is imperative to establish and implement effective conservation strategies at both local and regional levels. However, there is limited information, particularly within the Kathmandu Valley of Nepal, underscoring the significance of local-level habitat characterization for burrowing animals like pangolins. In this context, our study aimed to assess how anthropogenic and environmental factors influence the presence of Chinese pangolins along the elevational gradients of Chandragiri-Champadevi Hills, renowned for the scenic beauty and popular hiking trails within the valley. We conducted surveys of foraging and resting burrows at 72 plots distributed along 12 elevational line transects from 1500 to 2100 m elevational gradients of Chandragiri-Champadevi Hills. Notably, we observed pangolin burrows spanning from 1550 m to 2095 m. With increasing elevation, we recorded a decline in both foraging and resting burrow numbers. Furthermore, our findings indicated an increase in burrow numbers with increasing the distances from roads, whereas burrow numbers decreased with increasing proximity to human settlements. Interestingly, foraging burrows exhibited an increase with noise but a decrease with slope, while resting burrows showed an increase association with higher canopy and ground cover percentages. Our study shows the substantial anthropogenic disturbances in the habitats of Chinese pangolins in the Chandragiri-Champadevi Hills. We recommend managing the human-associated threats to ensure the species conservation at this site-specific area.

Prey selection by leopards (Panthera pardus fusca) in the mid-hill region of Nepal.

Information on prey selection and the diet of the leopard (Panthera pardus fusca) is essential for leopard conservation. We conducted an investigation into the prey species and the proportion of each species in the leopard's diet in a human-dominated mid-hill region of Nepal. The analysis of 96 leopard scats collected between August 2020 and March 2021 revealed that leopards consumed 15 prey species, including small- and medium-sized mammals and livestock. In addition to these prey species, we also found plastic materials, bird feathers, and some unidentified items in the leopard scats. Wild ungulates (such as barking deer, Muntiacus muntjak and wild boar, Sus scrofa) constituted only 10% of the biomass in the scats, while livestock contributed 27%, and other wild prey contributed 50%. Among all species, domestic goats had the highest relative biomass in the scats, followed by the jungle cat (Felis chaus), domestic dog (Canis familiaris), and large Indian civet (Viverra zibetha). Similarly, the Indian hare (Lepus nigricollis) had the highest proportion of relative individuals present in the scat samples, followed by the jungle cat and the large Indian civet. A lower proportion of biomass from wild ungulates in the leopard's diet and a higher dependency of the leopard on domestic prey and other wild prey indicate a shortage of medium-sized wild prey, such as barking deer and wild boar, in leopard habitats. Therefore, the conservation of wild prey species, especially medium-sized prey, is crucial for reducing the leopard's dependence on livestock and mitigating human-leopard conflicts in the future.

Population and conservation threats to the vulnerable Sarus crane Grus antigone in Nepal.

Globally, biodiversity is declining due to habitat loss and degradation, over-exploitation, climate change, invasive species, pollution, and infrastructure development. These threats affect the populations of large waterbird species, such as Sarus crane (Grus antigone), which inhabits agricultural-wetland ecosystems. Despite the burgeoning built-up areas and diminishing agricultural and wetland spaces, scant research investigates the impact of these changing land uses on the globally vulnerable Sarus crane in Nepal. During the pre-breeding season from April to June 2023, our comprehensive study meticulously scrutinized Sarus crane population status and factors associated with the occurrences and conservation challenges across 10 specific districts of Nepal. Our study documented a total of 690 individuals of Sarus cranes in five districts. The Lumbini Province has 685 individuals, occupying 11 roosting sites. Conversely, the remaining five districts have no Sarus cranes presence during this period. Wetland, farmland and built-up areas exhibited a significantly positive influence on Sarus crane occurrences in the Lumbini Province. Additionally, we recorded 47 fatalities of Sarus cranes over the past 13 years in the Lumbini Province due to electrocution and collisions. Our study provides a baseline dataset crucial for developing conservation policies, particularly during the dry season when Sarus crane populations tend to congregate in larger flocks. The adaptation of the Sarus crane to urbanized landscapes exposes them to several anthropogenic threats in the coming days. Therefore, protecting wetlands and farmland areas and adopting transboundary conservation approaches are imperative for the long-term conservation of the Sarus crane and its habitat.

Nursing home closures and access to post-acute care and long-term care services in rural areas.

PURPOSE: Nursing home closures have raised concerns about access to post-acute care (PAC) and long-term care (LTC) services. We estimate the additional distance rural residents had to travel to access PAC and LTC services because of nursing home closures. METHODS: We identify nursing home closures and the availability of PAC and LTC services in nursing homes, home health agencies, and hospitals with swing beds using the Medicare Provider of Services file (2008-2018). Using distances between ZIP codes, we summarize distances to the closest provider of PAC and LTC services for rural and urban ZIP codes with nursing home closures from 2008 to 2018 and no nursing homes in 2018. FINDINGS: Compared to urban ZIP codes, rural ZIP codes experiencing nursing home closure had higher distances to the closest nursing home providing PAC (6.4 vs. 0.94 miles; p < 0.05) and LTC services (7.2 vs. 1.1 miles; p < 0.05), and these differences remain even after accounting for the availability of home health agencies and hospitals with swing beds. Distances to the closest providers with PAC and LTC services were even higher for rural ZIP codes with no nursing homes in 2018. About 6.1%-15.7% of rural ZIP codes with a nursing home closure or with no nursing homes had no PAC or LTC providers within 25 miles. CONCLUSIONS: Nursing home closures increased distances to nursing homes, home health agencies, and hospitals with swing beds for rural residents. Access to PAC and LTC services is a concern, especially for rural areas with no nursing homes.

Occurrence and temporal overlap of sympatric jungle cats and leopard cats in Parsa‒Koshi Complex, Nepal.

Co-occurrence and spatial and temporal overlap of sympatric jungle and leopard cats are influenced by habitat preferences, and interspecific competition. Understanding these factors influence is crucial for developing effective conservation strategies. We conducted a camera survey in Parsa‒Koshi Complex (PKC), Nepal during December 2022-March 2023 to investigate factors influencing occupancy and spatial and temporal overlap between jungle cats (Felis chaus) and leopard cats (Prionailurus bengalensis). The mean detection probability (t = 0.664, p = 0.507) did not differ between jungle cats (p = 0.500 ± 0.289) and leopard cats (p = 0.501 ± 0.288); however, occupancy (t = 31.008, p < 0.001) was greater for jungle cats (ψ = 0.247 ± 0.020) than leopard cats (ψ = 0.178 ± 0.019). Jungle cats and leopard cats were positively associated with large predators, and jungle cats were positively associated with human presence and negatively associated with canopy cover. We observed high diel overlap between leopard cats and jungle cats (Dhat1 = 0.802, norm0CI: 0.720-0.884), with both species largely nocturnal. Co-existence of jungle cats and leopard cats in PKC appears to be facilitated by spatial segregation. These findings provide valuable insights into the complex ecological dynamics and interactions between sympatric jungle and leopard cats.

Serratia marcescens Endocarditis in Prosthetic Valves.

Serratia marcescens endocarditis is a rare occurrence. We describe a case of Serratia endocarditis in a patient with a prosthetic valve. The clinical course was complicated by widespread embolic phenomena causing stroke, gangrene of extremities, and septic emboli to the lungs, spleen, and eyes. She was not considered suitable for surgery due to severe consumptive coagulopathy and thrombocytopenia in the setting of widespread emboli. The patient was transitioned to do not resuscitate status and discharged to a long-term care facility with a grave prognosis explained to the family.

Prevalence, Correlates, and Perception of E-cigarettes among Undergraduate Students of Kathmandu Metropolitan City, Nepal: A Cross-Sectional Study.

Introduction: The use of e-cigarettes has been increasing globally especially among the youth population due to rigorous advertisement, marketing, and promotion which has become a significant public health concern. Hence, this study is aimed at identifying the prevalence, correlates, and perception of e-cigarettes among undergraduate students of Kathmandu city. Methods: A cross-sectional study was conducted among 405 undergraduates of capital city of Nepal from April 2022 to December 2022. A two-stage systematic random sampling was used to select the respondents. An anonymous, semistructured, self-administered questionnaire was used for data collection. A descriptive, bivariable, and multivariable analysis was done using SPSS version 20. Results: The prevalence of ever use and current use of e-cigarettes was 21.2% and 5.9%, respectively. Number of close friends (AOR = 5.23, CI: 1.26, 16.39), number of friends using e-cigarettes (AOR = 7.23, CI: 0.93, 22.82), male sex (AOR = 2.88, CI: 2.15, 10.35), and age (COR = 5.07, CI: 0.93, 8.19) were the major predictors of current e-cigarette usage. Similarly, number of friends using e-cigarettes (AOR = 5.90, CI: 2.15, 10.35), male sex (AOR = 3.53, CI: 2.15, 10.35), age (COR = 4.56, CI: 0.98, 6.24), and place of residence (COR: 5.19, CI: 0.83, 8.02) were the major predictors of ever e-cigarette usage. The prevalence of e-cigarette consumption was higher in males than females (5.4% vs. 0.5%). Approximately, 34.8% respondents had perceived e-cigarettes as a means to help in smoking cessation. 56.5% adults knew that e-cigarettes promoted conventional smoking. Majority (64.7%) of the undergraduate students had presumed e-cigarettes as less harmful to conventional smoking. Conclusion: Ever use, current use, and misconception on e-cigarettes were widespread among the undergraduate students. Age, male sex, number of close friends, number of peers using e-cigarette, and place of residence were the major predictors for e-cigarette usage. To deal with the increased e-cigarette consumption state, awareness on the harmful addictive properties of e-cigarettes along with its adverse health consequences must be propagated and an appropriate intervention must be implemented.

Factors affecting the occupancy of sloth bear and its detection probability in Parsa-Koshi Complex, Nepal.

Understanding factors associated with coexistence of human and wildlife in human-dominated landscapes is crucial for effective species conservation. Among the wildlife species, the sloth bears Melursus ursinus are found both inside and outside the protected areas of Nepal, and with increasing cases of human and bear conflicts in both areas. This highlights the necessity for a comprehensive understanding of anthropogenic and ecological factors that affect the occurrence of sloth bear. The understanding of these factors is important for its coexistence and conservation in human-dominated areas through establishing management and conservation action plan. We studied the sloth bear's occupancy and their coexistence in human-dominated environments with other large predators in the Parsa-Koshi Complex of Nepal using camera traps from December 2022 to March 2023. We identified the occupancy and detection probability of the sloth bear as 0.12 and 0.31, respectively. Our analysis reveals a positive relationship between sloth bear occurrence and the presence of large predators (ßpredators = 3.104 ± 0.968), such as tigers (Panthera tigris) and leopards (Panthera pardus), as well as the number of humans detected (ßhuman = 1.428 ± 1.216) and canopy cover percentage (ßcc = 1.002 ± 0.737). However, the number of livestock detected shows a negative interaction with the occurrence of sloth bears (ßlivestock = -2.240 ± 1.467). There was insignificant interaction between sloth bear occupancy and distance to human settlements, roads, and water bodies. These findings underscore the complex dynamics between sloth bears, humans, large predators, and livestock in human-dominated landscapes. To ensure the long-term survival of sloth bear populations and promote species conservation, comprehensive conservation strategies that account for both ecological and socio-economic factors are essential.

Sleep deprivation enhances amyloid beta peptide, p-tau and serotonin in the brain: Neuroprotective effects of nanowired delivery of cerebrolysin with monoclonal antibodies to amyloid beta peptide, p-tau and serotonin.

Sleep deprivation is quite frequent in military during combat, intelligence gathering or peacekeeping operations. Even one night of sleep deprivation leads to accumulation of amyloid beta peptide burden that would lead to precipitation of Alzheimer's disease over the years. Thus, efforts are needed to slow down or neutralize accumulation of amyloid beta peptide (AßP) and associated Alzheimer's disease brain pathology including phosphorylated tau (p-tau) within the brain fluid environment. Sleep deprivation also alters serotonin (5-hydroxytryptamine) metabolism in the brain microenvironment and impair upregulation of several neurotrophic factors. Thus, blockade or neutralization of AßP, p-tau and serotonin in sleep deprivation may attenuate brain pathology. In this investigation this hypothesis is examined using nanodelivery of cerebrolysin- a balanced composition of several neurotrophic factors and active peptide fragments together with monoclonal antibodies against AßP, p-tau and serotonin (5-hydroxytryptamine, 5-HT). Our observations suggest that sleep deprivation induced pathophysiology is significantly reduced following nanodelivery of cerebrolysin together with monoclonal antibodies to AßP, p-tau and 5-HT, not reported earlier.

Advances in Neurorestoratology-Current status and future developments.

Neurorestoratology constitutes a novel discipline aimed at the restoration of damaged neural structures and impaired neurological functions. This area of knowledge integrates and compiles all concepts and strategies dealing with the neurorestoration. Although currently, this discipline has already been well recognized by physicians and scientists throughout the world, this article aimed at broadening its knowledge to the academic circle and the public society. Here we shortly introduced why and how Neurorestoratology was born since the fact that the central nervous system (CNS) can be repaired and the subsequent scientific evidence of the neurorestorative mechanisms behind, such as neurostimulation or neuromodulation, neuroprotection, neuroplasticity, neurogenesis, neuroregeneration or axonal regeneration or sprouting, neuroreplacement, loop reconstruction, remyelination, immunoregulation, angiogenesis or revascularization, and others. The scope of this discipline is the improvement of therapeutic approaches for neurological diseases and the development of neurorestorative strategies through the comprehensive efforts of experts in the different areas and all articulated by the associations of Neurorestoratology and its journals. Strikingly, this article additionally explores the "state of art" of the Neurorestoratology field. This includes the development process of the discipline, the achievements and advances of novel neurorestorative treatments, the most efficient procedures exploring and evaluating outcome after the application of pioneer therapies, all the joining of a multidisciplinary expert associations and the specialized journals being more and more impact. We believe that in a near future, this discipline will evolve fast, leading to a general application of cell-based comprehensive neurorestorative treatments to fulfill functional recovery demands for patients with neurological deficits or dysfunctions.

Positive and negative cell therapy in randomized control trials for central nervous system diseases.

Neurorestorative cell therapies have been tested to treat patients with nervous system diseases for over 20 years. Now it is still hard to answer which kinds of cells can really play a role on improving these patients' quality of life. Non-randomized clinical trials or studies could not provide strong evidences in answering this critical question. In this review, we summarized randomized clinical trials of cell therapies for central nervous diseases, such as stroke, spinal cord injury, cerebral palsy (CP), Parkinson's disease (PD), multiple sclerosis (MS), brain trauma, amyotrophic lateral sclerosis (ALS), etc. Most kinds of cell therapies demonstrated negative results for stoke, brain trauma and amyotrophic lateral sclerosis. A few kinds of cell therapies showed neurorestorative effects in this level of evidence-based medicine, such as olfactory ensheating cells for chronic ischemic stroke. Some kinds of cells showed positive or negative effects from different teams in the same or different diseases. We analyzed the possible failed reasons of negative results and the cellular bio-propriety basis of positive results. Based on therapeutic results of randomized control trials and reasonable analysis, we recommend: (1) to further conduct trials for successful cell therapies with positive results to increase neurorestorative effects; (2) to avoid in repeating failed cell therapies with negative results in same diseases because it is nonsense for them to be done with similar treatment methods, such as cell dosage, transplanting way, time of window, etc. Furthermore, we strongly suggest not to do non-randomized clinical trials for cells that had shown negative results in randomized clinical trials.