A true shift in stroke epidemiology is also possible. As several vaccines become more readily available and the world rebounds from this pandemic, we hope to transform the neurointerventional experiences discussed in this paper into strategies that may improve care delivery of neurologically ill patients during a global crisis.Introduction Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus and the leading cause of blindness in young adults. Prior to anti-vascular endothelial growth factor (anti-VEGF) agents, the treatment of DR was based on control of systemic factors and laser photocoagulation. Over the past decade, the use of anti-VEGF agents has revolutionized the treatment of DR, including diabetic macular edema (DME).Areas covered Ranibizumab has been proven to be effective for the treatment of DME in large clinical trials, while patients in these studies have been assessed in terms of DR severity change. In this review, evidence from randomized trials regarding the use of ranibizumab for DR treatment is presented.Expert opinion A comprehensive presentation of randomized clinical trials evaluating ranibizumab for DR indicates that it is effective and safe, offering improvement of DR severity in both non-proliferative and proliferative forms. However, there is no general consensus regarding the exact treatment regimen in patients with DR, while the effect of ranibizumab on the progression of retinal ischemia remains unclear.There is a growing need for clean and green labeling of food products among consumers globally. Therefore, development of green modified starches, to boost functionality, palatability and health benefits while reducing the negative processing impacts on the environment and reinforcing consumer safety is in high demand. Starch modification started in mid-1500s due to the inherent limitations of native starch restricting its commercial applications, with chemical modification being most common. However, with the recent push for "chemical-free" labeling, methods of physical and enzymatic modification have gained immense popularity. These methods have been successfully used in numerous studies to alter the composition, structure, functionality and digestibility of starch and in this review, studies reported on green modification of cassava starch, one of the most common utilized starches, within the last ten years have been critically reviewed. Recent research has introduced starch as an abundant, natural substrate for producing resistant starches through biophysical technologies that act as dietary fiber in the human body. It is evident that different techniques and processing parameters result in varying degrees of modification impacting the techno-functionality and digestibility of the resultant starch. This can be exploited by researchers and industrialists in order to customize starch functionality in accordance with application.When an adverse event occurs after a dermal filler treatment, simple ultrasound can be of help for diagnosis. https://www.selleckchem.com/products/mitopq.html But sometimes a more sophisticated imaging technique as MRI is needed to find the true reason for a complication. As in the case of pneumosinus dilatans after injection of a dermal filler, we present. The relation of this rare disorder and filler injection is discussed.This study aimed to explore the relationship between chronotype and resilience, sleep quality, and post-traumatic stress reactions during the first COVID-19 lockdown in Italy. An online survey was distributed through social networks during forced home confinement, collecting data from1298 participants of 19 different Italian regions. Chronotype was evaluated using the reduced version of the Morningness/Eveningness Questionnaire (rMEQ); sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI); resilience levels were measured by the 10-item version of the Connor-Davidson Resilience Scale (CD-RISC10); post-traumatic stress reactions were assessed by the 6-item version of the Impact of Event Scale (IES6). Resilience and sleep quality were significantly lower in the evening compared to non-evening types, as well as in females as compared to males. Moreover, resilience was negatively correlated with post-traumatic stress reactions and positively correlated with sleep quality. A negative correlation was also reported between sleep quality and post-traumatic stress reactions. Sleep quality was identified as a possible mediator between chronotype and resilience, and between resilience and post-traumatic stress reactions, after controlling for age and sex. These findings provide new insights into the role of chronotype in adapting to continuous stressful situations. Sleep quality seems to mediate the causal path between the antecedents of resilience and the development of trauma. Further research is needed to explore the suitability of primary interventions based on chronobiology and sleep hygiene to mitigate the impact of pandemic-related home confinement measures on mental health among the general population.
Pregnant women and foetuses are more likely than ever to be exposed to antipsychotic drugs (APs) during pregnancy and post-partum period. Second-generation APs (SGA) are increasingly used among women in reproductive age. Key outcomes (i.e. congenital malformations, pregnancy and maternal outcomes, neonatal/infant risks and developmental/long-term outcomes) following the exposure to APs remain limited in number and size and yield of inconsistent findings overall, particularly regarding long-acting injectable AP (LAI-APs) formulations.

The review aims at providing a summary of current knowledge on potential risks and safety profile of LAI-APs during pregnancy and breastfeeding, specifically focusing on SGA.

The management of safety and tolerability of long-acting injectable AP (LAI-APs) is far from having solid scientific evidence. In fact, due to ethical reasons, there is a lack of randomized clinical trials that limits the reliability and generalizability of the available data on LAI-APs safety profile nt outcomes.The aim of this study was to determine the molecular spectrum of β-thalassemia (β-thal) mutations in eastern Thailand. We identified β-thal mutations using allele specific-polymerase chain reaction (ASPCR) and direct DNA sequencing. We found 18 different β-thal mutations in a total of 191 unrelated subjects. Six common β-thal mutations comprised 86.91% of all the mutations, including codons 41/42 (-TTCT) (HBB c.126_129delCTTT) (35.60%), codon 17 (A>T) (HBB c.52A>T) (18.85%), -28 (A>G) (HBB c.-78A>G) (15.71%), IVS-II-654 (C>T) (HBB c.316-197C>T) (6.28%), IVS-I-1 (G>T) (HBB c.92+1G>T) (5.76%) and codon 19 (A>G) (HBB(c.59A>G) (4.71%). In addition, a novel 60 kb deletion in two unrelated cases was characterized and initially suspected to originate from eastern Thailand. Moreover, we demonstrated the molecular spectrum of recent β-thal mutations in Thailand, and data from this study were compared with five reference laboratory centers in Thailand. This study is the first to identify the comprehensive molecular spectrum of β-thal mutations in eastern Thailand, information that may be essential for screening, genetic counseling and prenatal diagnosis (PND) in this region.

08% (10th and 90th percentiles -1.8% and 1.6%). In the regression model comparing the RSMR between two models, the slope and intercept of the regression equation is 0.90 and 0.007 in modelling cohort, while 0.85 and 0.010 in validation cohort, which indicated that the evaluation capability from two models were very similar.

The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.
The models based on MRFP data showed good discrimination and calibration capability, as well as similar risk prediction effect in comparison with the model based on complete medical record data, which proved that MRFP data could be suitable for risk adjustment in hospital performance measurement.
To conduct a scoping review that (1) describes what is known about the relationship between athletic identity and sport-related injury outcomes and (2) describes the relationship that an injury (as an exposure) has on athletic identity (as an outcome) in athletes.

Scoping review.

A total of n=1852 athletes from various sport backgrounds and levels of competition.

The primary measure used within the studies identified was the Athletic Identity Measurement Scale. Secondary outcome measures assessed demographic, psychosocial, behavioural, physical function and pain-related constructs.

Twenty-two studies were identified for inclusion. Samples were dominated by male, Caucasian athletes. The majority of studies captured musculoskeletal injuries, while only three studies included sport-related concussion. Athletic identity was significantly and positively associated with depressive symptom severity, sport performance traits (eg, ego-orientation and mastery-orientation), social network size, physical self-wnterest for further exploration.
This study was aimed to assess the magnitude and associated factors of unmet need for family planning among rural women in Ethiopia.

Cross-sectional study.

Ethiopia.

Reproductive age group women.

Unmet need for family planning.

This study drew data from Ethiopian Demographic and Health Survey, which was conducted from 18 January to 27 June 2016. A total of 8327 rural reproductive-aged (15-49 years) women were included. A two-level multivariable logistic regression model was carried out to identify individual and community-level factors associated with unmet need for family planning. Adjusted OR (AOR) with a 95% CI was used to assess the strength of association between independent and dependent variables.

The overall unmet need for family planning among rural women was 24.08% (95% CI 23.17 to 25.01), of which 14.79% was for spacing and 9.29% for limiting. Number of children (AOR=1.15; 95% CI 1.07 to 1.24) and working status of women (AOR=1.18; 95% CI 1.02 to 1.37) were significantly associated wi family planning, public health policymakers should consider both individual and community-level factors when designing FP programmes and emphasis should be given to high-risk populations.
Unmet need for family planning among reproductive-aged women in rural Ethiopia was high. Number of children, working status of women, women's education, age at first marriage, household wealth, distance to a health facility, community women's education and community media exposure were significantly associated with unmet needs for family planning. Therefore, to reduce unmet need for family planning, public health policymakers should consider both individual and community-level factors when designing FP programmes and emphasis should be given to high-risk populations.
With the acute shortage of human resources and infrastructure, mobile phones can be a critical tool for accessing health services and strengthening health systems in Bangladesh. Yet, there is a scarcity of evidence on the use of mobile phones in this context for accessing health services. In this study, we sought to explore the current use of mobile phones for accessing maternal and child healthcare and its determinants among recently delivered women in urban slums of Bangladesh.

The data were collected through interviewing 800 recently delivered women from eight slums of Dhaka city of Bangladesh during May and June 2018. The study followed a cross-sectional design and a two-stage cluster random sampling procedure was followed. A pretested structured questionnaire was employed to collect information. Chi square tests were performed for descriptive analyses and a multilevel binary logistic regression model was executed to explore the determinants of mobile phone usage for accessing maternal and childcare ain slum settlements for accessing maternal and child healthcare and is a sustainable mitigation strategy for the acute health worker crisis in Bangladesh. The findings of this study are particularly crucial for policymakers and practitioners while they revise the health policy to incorporate mHealth interventions as highlighted in the recently initiated Digital Health Strategy of Bangladesh.
This study aims to investigate the effects of an optimal home-based respiratory care protocol in individuals with amyotrophic lateral sclerosis (ALS).

This is a randomised, blinded controlled trial involving patients diagnosed with ALS, both sexes, age between 18 and 80 years. Patients will be randomly allocated into the conventional respiratory care (CRC) group and the optimised respiratory care home-based (ORC) group. Primary outcomes will be peak cough flow, the number of exacerbations and ALS Functional Rating Scale Revised. Secondary outcomes will include chest wall volumes, maximal respiratory pressures, sniff nasal inspiratory pressure, nasal expiratory pressure and forced vital capacity (FVC), forced expiratory volume in the 1st second (FEV
) and FEV
/FVC. The CRC group will receive educational information about respiratory care at the clinic. https://www.selleckchem.com/products/azd9291.html The ORC group will receive conventional care and home-based care. The clinical status of all individuals will be monitored weekly through telephone calls.

How to Maintain a Frost Free Fridge and Freezer

Defrosting isn't necessary when you have a frost-free refrigerator or freezer. This can save you time, effort and electricity when compared to a traditional refrigerator/freezer.

If you notice ice crystals on the packaging frozen food items can be damaged. These crystals can cause damage to your food and alter the texture of your food.

Defrost



The process of defrosting your freezer isn't fun or glamorous however it's an essential aspect of fridge and freezer maintenance. Warm air is dragged into the freezer each time you open it, causing condensation and frozen surfaces. The frost can hinder the freezer's ability to regulate temperature, making it work overtime and consume more energy. It can also compromise the flavor and quality of food, and lead to freezer burn.

The best way to defrost the freezer is to let it melt naturally, but this can take several hours. In the event of a crisis, a hairdryer or handheld steam cleaner can accelerate the process. Be sure to unplug and shut off the freezer before beginning. Get rid of all frozen food and clean up any water spilled.

Make sure to have towels, or a plastic liner prepared prior to starting the process of defrosting. This will catch any water that may spill. It's a good idea to empty the entire freezer to allow you to reorganize the food left and dispose of old or expired items. When the defrosting process has been complete, make sure to thoroughly clean and dry your freezer before turning it on.

To speed up the natural process of defrosting, open and close the door to your freezer several times to let the temperature rise. Remove all shelves and drawer compartments to give yourself easier access to the ice. You can also lay old towels or newspapers which are very absorbent on the floor to soak up any puddles created by melting the ice.

As the ice melts, be sure to keep a warm spoon or plastic spatula handy to break up any large chunks that build up on interior walls. Avoid sharp objects like forks, knives, or ice picks when trying to break through the ice. This can cause damage and leaks into the freezer. Don't forget to wipe down and rinse the removable shelves and drawers after the ice has gone. Once everything is clean Plug in the freezer and let it run for a night to return to its normal freezing temperature.

Clean

Regular cleaning is the best way to prevent spores and food odors from building up. Remove any produce that has gone bad or is beyond its prime and dispose of it. Wipe down all drawers and shelves with soapy water using a damp cloth (I use Seventh Generation Natural Dish Liquid). Then dry them. I also wipe down the freezer with a clean cloth that is dipped in a solution of baking soda and vinegar or water. Scrubbing stubborn stains with a non-scratch brush may be necessary. https://output.jsbin.com/libulabaje/ at the back of my refrigerator using a spray. This removes all pet fur, dirt and dust that gets stuck in difficult to reach places.

If you have a frost free refrigerator, you will not need to defrost it as often as other models. Frost free fridges have an automatic cooling mechanism that cools the food by circulating cold air through the refrigerator, eliminating the necessity of manually defrosting the appliance. It is nevertheless important to clean the refrigerator once a week, tossing any food items that are past the expiration date and getting rid of all the old jars, bottles and soy sauce packets.

To make defrosting simpler take the contents out of your freezer and temporarily place them in another freezer, a cooler containing ice packs, or a box covered with blankets. During this process, be sure to shield the floor of your freezer using an old towel on the bottom. When the freezer is defrosted, you can scrape off any remaining ice using an ice scraper made of plastic.

If your refrigerator is equipped with an automatic defrost feature you will see an indicator light that will inform you when it's time to defrost. To avoid losing any frozen items during the defrost process, you can empty the freezer and set it on a counter. You can then restock it with frozen food that has a long shelf life. You can then make use of an old towel to catch any water that drips from the freezer as it melts.

Maintaining

If frost covers the evaporator and it freezes, it will. This causes the fridge to work more and use more energy. This is why maintaining it regularly is so important. Unplugging the freezer and cleaning the evaporator coil will stop this from occurring in the first place.

If the defrost system is operating properly the frost layer should develop on the evaporator in an even pattern. If there is an accumulation of ice on the evaporator that is not caused by problems with defrost, it may be a sign of a defective timer or defrost termination thermostat.

Some older models can have a clogged supply as well as return air duct from the freezer and back to it. This can be caused by pet hair or food residue. This makes the compressor work harder, and it produces excess heat. The heat then move into the refrigerator cabinet, causing temperatures to rise. This issue can be cured by ensuring that the gasket for the freezer door isn't damaged and is properly sealed.

Frequent opening of the freezer can allow humid air into the appliance, creating an environment where ice and frost are more likely to form. The freezer should be kept tightly closed to reduce the chance of ice and frost forming.

Regularly clean the evaporator drainage tube to ensure it is not clogged with food debris or ice. This can be done using handheld vacuum cleaners or a coil cleaner designed specifically for refrigerators (usually using a brush that is able to get into hard to reach areas).

Make sure the freezer is free of any obstructions that might hinder air flow or obstruct the condenser fan. To remove food particles and eliminate odours, wash the interior walls and shelves using a mix of hot dish soap, water or baking powder. Air vents in the freezer and refrigerator compartments should not be blocked as this could result in inadequate circulation of air, which could increase the humidity inside the appliance.

Repair

There are a myriad of reasons your fridge freezer that is frost-free may not be functioning properly. Most of them are simple and simple to fix, however some require the help of a professional. The issue is typically caused by something that prevents air from moving into and from freezer section. This could be caused by over-packed food packages, clogged ventilation gaps and/or keeping the door open for too long.

Unplug your refrigerator prior to performing any maintenance or repairs. This will reduce the chance of an electric shock, and let any frost melt by itself.

If the refrigerator isn't cooling it could be due to a problem with the defrost. This type of fridge and freezer automatically activates a heater to melt any frost on the evaporator. The melted snow drains down a drain pipe into an unintended pan located at the back of the refrigerator and it then evaporates into the air. The timer for defrost could be malfunctioning and need to be replaced.

It's also possible that a bad seal is blocking cold air from entering the freezer compartment of your refrigerator. It can be repaired by cleaning the seal using warm water and a bit of soap. Make sure there are no items blocking the freezer vents or rubbing against the back wall of the refrigerator.

If the gasket is worn or damaged, you can try to replace it. Most major appliance makers provide replacement parts for their products directly including freezer gaskets. It is important to remember that only a certified professional can replace the gasket in a freezer.

Alternatively, you may be experiencing a problem with the evaporator fan that circulates the air in your freezer section of your fridge. There is a clicking noise when the fan is turned on. The evaporator's ice has grown too thick and is causing the fan blades to be damaged. This is a problem that will need to be identified by a qualified technician.

To investigate the burden of mortality due to ischemic heart disease (IHD) attributable to low levels of physical activity in the Brazilian population (aged ≥ 25 years) before, during and after economic and political crises (2007-2017).

This study was focused on IHD as a cause of death. The International Statistical Classification of Diseases (10th revision) codes related to IHD have been mapped. The data used for the physical activity estimates of the present study refer to surveys with random sampling carried out in the Brazilian territory that considers all domains of physical activity. The contribution of physical activity for mortality due to IHD was estimated using a comparative risk assessment approach. In addition, we verified the association between mortality due to IHD attributable to low levels of physical activity according to the Socio-demographic Index of the Brazilian states.

For males it was estimated that in 2007 and 2017 there were, respectively, 9,585 and 11,821 deaths due to IHD as amic and political crisis highlighted the social inequalities between Brazilian geographic regions for the burden of mortality due to IHD attributable to low levels of physical activity.
Dispersal is an important process affecting population dynamics and connectivity. For marine direct developers, both adults and juveniles may disperse. Although the distribution of juveniles can be initially constrained by their mothers' choice, they may be able to leave the parental habitat and colonize other habitats. We investigated the effect of habitat quality, patch size and presence of conspecific adults on the colonization of novel habitats by juveniles of the tube-dwelling amphipod
associated with the macroalgal host
.

We tested the factors listed above on the colonization of juveniles by manipulating natural and artificial plants in both the field and laboratory.

In the laboratory, juveniles selected high-quality habitats (i.e., natural alga), where both food and shelter are provided, when low-quality resources (i.e., artificial alga) were also available. In contrast, habitat quality and algal patch size did not affect the colonization by juveniles in the field. Finally, the presence of cgest that C. filosa juveniles can select and colonize novel habitats, and that such process can be partially affected by habitat quality, but not by patch size. Also, the presence of conspecifics may affect the colonization by juveniles. Successful colonization by this specific developmental stage under different scenarios indicates that juveniles may act as a dispersal agent in this species.Maternal thyroid hormones (THs) are known to be crucial in embryonic development in humans, but their influence on other, especially wild, animals remains poorly understood. So far, the studies that experimentally investigated the consequences of maternal THs focused on short-term effects, while early organisational effects with long-term consequences, as shown for other prenatal hormones, could also be expected. In this study, we aimed at investigating both the short- and long-term effects of prenatal THs in a bird species, the Japanese quail Coturnix japonica. We experimentally elevated yolk TH content (the prohormone T4, and its active metabolite T3, as well as a combination of both hormones). We analysed hatching success, embryonic development, offspring growth and oxidative stress as well as their potential organisational effects on reproduction, moult and oxidative stress in adulthood. We found that eggs injected with T4 had a higher hatching success compared with control eggs, suggesting conversion of T4 into T3 by the embryo. We detected no evidence for other short-term or long-term effects of yolk THs. These results suggest that yolk THs are important in the embryonic stage of precocial birds, but other short- and long-term consequences remain unclear. Research on maternal THs will greatly benefit from studies investigating how embryos use and respond to this maternal signalling. Long-term studies on prenatal THs in other taxa in the wild are needed for a better understanding of this hormone-mediated maternal pathway.Hepatocellular carcinoma is the most common type of primary liver cancer in humans. This study aimed to demonstrate anticancer properties of an aqueous extract from Chrysophyllum cainito stem bark (CE) and its underlying mechanisms. Our MTT assay results showed that CE significantly reduced human hepatocellular carcinoma (HepG2) cell viability with the IC50of 100 µg/mL, while human dermal primary fibroblast (HDFa) cells showed less susceptibility in every concentration tested. Determined by Annexin V staining, the proportion of apoptotic HepG2 cells increased in a dose-dependent fashion after 24 hour-exposure of CE. The results from Western blot analysis confirmed that CE reduced procaspase-3, suggesting apoptosis by activating caspase-3 cleavage. Using the DCFH-DA and DiOC6 fluorescent probes, it was found that CE significantly stimulated the generation of reactive oxygen species (ROS) and reduced mitochondrial membrane potential (Δψm), respectively. According to cell cycle analysis, CE (100 µg/mL) profoundly increased the percentage of cells in the sub-G1 phase, indicating cell apoptosis. These data suggest that CE induces apoptosis and cell death in human hepatocellular carcinoma via generation of intracellular ROS and disruption of Δψm. This is the first demonstration of the anticancer activity with proposed underlying mechanism of CE in liver cancer cells.
The COVID-19 pandemic is found to affect the mental health of the population. Undergraduate medical students are especially prone to mental health disorders and hence could be more vulnerable to the impact of the pandemic.

A prospective longitudinal study was conducted on 217 undergraduate medical students in a medical college at Chennai, India. Depression, anxiety, and stress levels were recorded using Depression Anxiety Stress Scale 21 Items (DASS21) before and during the COVID-19 outbreak in India in December 2019 and June 2020, respectively. https://www.selleckchem.com/products/tpca-1.html In the follow-up survey, in addition to DASS21, the Pittsburgh Sleep Quality Index to assess sleep quality and a self-administered questionnaire to assess the impact of COVID-19 related stressors were used. The self-administered questionnaire assessed the status of COVID-19 testing, interactions with COVID-19 patients, self-perceived levels of concerns and worries related to academics (COVID-19-AA (academic apprehensions)) and those pertaining to the self and family/friends (COVID-19-GA (general apprehensions)).

Variation in the mitochondrial DNA (mtDNA) sequence is common in certain tumours. Two classes of cancer mtDNA variants can be identified de novo mutations that act as 'inducers' of carcinogenesis and functional variants that act as 'adaptors', permitting cancer cells to thrive in different environments. These mtDNA variants have three origins inherited variants, which run in families, somatic mutations arising within each cell or individual, and variants that are also associated with ancient mtDNA lineages (haplogroups) and are thought to permit adaptation to changing tissue or geographic environments. In addition to mtDNA sequence variation, mtDNA copy number and perhaps transfer of mtDNA sequences into the nucleus can contribute to certain cancers. https://www.selleckchem.com/products/dorsomorphin-2hcl.html Strong functional relevance of mtDNA variation has been demonstrated in oncocytoma and prostate cancer, while mtDNA variation has been reported in multiple other cancer types. Alterations in nuclear DNA-encoded mitochondrial genes have confirmed the importance of mitochondrial metabolism in cancer, affecting mitochondrial reactive oxygen species production, redox state and mitochondrial intermediates that act as substrates for chromatin-modifying enzymes. Hence, subtle changes in the mitochondrial genotype can have profound effects on the nucleus, as well as carcinogenesis and cancer progression.Evaluating the biomechanics of soft tissues at depths well below their surface, and at high precision and in real time, would open up diagnostic opportunities. Here, we report the development and application of miniaturized electromagnetic devices, each integrating a vibratory actuator and a soft strain-sensing sheet, for dynamically measuring the Young's modulus of skin and of other soft tissues at depths of approximately 1-8 mm, depending on the particular design of the sensor. We experimentally and computationally established the operational principles of the devices and evaluated their performance with a range of synthetic and biological materials and with human skin in healthy volunteers. Arrays of devices can be used to spatially map elastic moduli and to profile the modulus depth-wise. As an example of practical medical utility, we show that the devices can be used to accurately locate lesions associated with psoriasis. Compact electronic devices for the rapid and precise mechanical characterization of living tissues could be used to monitor and diagnose a range of health disorders.In patients with glioblastoma, resistance to the chemotherapeutic temozolomide (TMZ) limits any survival benefits conferred by the drug. Here we show that the convection-enhanced delivery of nanoparticles containing disulfide bonds (which are cleaved in the reductive environment of the tumour) and encapsulating an oxaliplatin prodrug and a cationic DNA intercalator inhibit the growth of TMZ-resistant cells from patient-derived xenografts, and hinder the progression of TMZ-resistant human glioblastoma tumours in mice without causing any detectable toxicity. Genome-wide RNA profiling and metabolomic analyses of a glioma cell line treated with the cationic intercalator or with TMZ showed substantial differences in the signalling and metabolic pathways altered by each drug. Our findings suggest that the combination of anticancer drugs with distinct mechanisms of action with selective drug release and convection-enhanced delivery may represent a translational strategy for the treatment of TMZ-resistant gliomas.Totipotent cells hold enormous potential for regenerative medicine. Thus, the development of cellular models recapitulating totipotent-like features is of paramount importance. Cells resembling the totipotent cells of early embryos arise spontaneously in mouse embryonic stem (ES) cell cultures. Such '2-cell-like-cells' (2CLCs) recapitulate 2-cell-stage features and display expanded cell potential. Here, we used 2CLCs to perform a small-molecule screen to identify new pathways regulating the 2-cell-stage program. We identified retinoids as robust inducers of 2CLCs and the retinoic acid (RA)-signaling pathway as a key component of the regulatory circuitry of totipotent cells in embryos. Using single-cell RNA-seq, we reveal the transcriptional dynamics of 2CLC reprogramming and show that ES cells undergo distinct cellular trajectories in response to RA. Importantly, endogenous RA activity in early embryos is essential for zygotic genome activation and developmental progression. Overall, our data shed light on the gene regulatory networks controlling cellular plasticity and the totipotency program.The intensification of food production plays a central role in the evolution of complex human societies. However, it is unclear whether the standard model of intensification is theoretically or empirically justified. This leaves social scientists unable to make reasonable inferences about the relationship between intensification and the evolution of social complexity in past societies. To remedy this problem, I derive a model of intensification from human macroecology, settlement scaling theory, human behavioural ecology, cultural evolutionary theory and niche construction theory. The standard and cultural niche construction models are formalized and their predictions are tested using a comprehensive ethnographic dataset that describes food production in 40 human societies, ranging in complexity from foraging bands to agricultural states. Analysis of the ethnographic record suggests that we reject the standard model and tentatively accept the cultural niche construction model. I attempt to demonstrate the broader utility of the cultural niche construction model as a framework that may help explain the transition from small-scale to large-scale complex societies.In times of crisis, risk pooling can enhance the resilience of individuals, households and communities. Risk-pooling systems are most effective when their participants adhere to several principles (1) participants should agree that the pool is for needs that arise unpredictably, not for routine, predictable needs; (2) giving to those in need should not create an obligation for them to repay; (3) participants should not be expected to help others until they have taken care of their own needs; (4) participants should have a consensus about what constitutes need; (5) resources should be either naturally visible or made visible to reduce cheating; (6) individuals should be able to decide which partners to accept; and (7) the scale of the network should be large enough to cover the scale of risks. We discuss the cultural and evolutionary foundations of risk-pooling systems, their vulnerabilities and their relationship to commercial insurance.