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The development of novel therapeutics is associated with high rates of attrition, with unexpected adverse events being a major cause of failure. Serious adverse events have led to organ failure, cancer development and deaths that were not expected outcomes in clinical trials. These life-threatening events were not identified during therapeutic development due to the lack of preclinical safety tests that faithfully represented human physiology. We highlight the successful application of several novel technologies, including high-throughput screening, organs-on-chips, microbiome-containing drug-testing platforms and humanised mouse models, for mechanistic studies and prediction of toxicity. We propose the incorporation of similar preclinical tests into future drug development to reduce the likelihood of hazardous therapeutics entering later-stage clinical trials.

Purpose This study aimed to investigate the medical care provided at the venue of the weightlifting event of the Tokyo 2020 Olympic Games. Methods We retrospectively evaluated athletes who availed of medical services at the venue during the weightlifting event of the Tokyo 2020 Olympic Games. In total, 194 athletes participated in the weightlifting competition. Injuries and illnesses were classified into cases handled without physician or cases requiring medical examination by a physician. These were tabulated for each examination location (athlete medical station, field of play [FOP], first-aid station of training floor or warm-up area). Results Throughout the event, a cumulative total of 132 people used the venue medical services. Nine athletes required medical attention at the athlete medical stations. Of these nine cases, six occurred on the training floor. In the FOP, nine athletes were examined. Two experienced light-headedness, two had knee pain, and the rest had other symptoms. No athletes wanted to undergo medical examination at the athlete medical station. 89 medical procedures were performed in the first-aid station on the training floor, including 52 tapings and 37 ice compressions, and the most frequent body part which needed treatment was the knee, followed by the fingers. At the first-aid station on the match floor, 25 medical procedures were performed, including 17 ice compressions, 5 haemostasis, and 4 tapings. The body parts that most frequently needed treatment were the fingers, knees, and lower legs. Conclusion Several athletes needed treatment; however, only a few required medical care from a physician.

Using the empirical or phenomenological research method by observing the effects of drugs in the human physiology, Samuel Hahnemann proposed the homeopathic treatment. He synthesized modern pharmacodynamic in the ‘primary action’ of the drugs and in the consequent and opposite ‘secondary action’ or ‘vital reaction’ of the organism. Noting that drugs with ‘contrary’ primary action to the symptoms of the diseases caused worsening of the symptoms after its withdrawal, as a result of secondary action of the organism, Hahnemann proposed using this vital reaction in a curative way, administering to sick individuals the drugs that caused ‘similar’ symptoms in healthy individuals (therapeutic use of the similitude principle). According to the clinical and experimental pharmacology, this secondary action (vital reaction) of the organism is observed in the ‘rebound effect’ or ‘paradoxical reaction’ of several classes of drugs, which is the scientific basis of the ‘homeopathic pharmacology’. In the last decade, exponents of modern pharmacology have suggested the therapeutic use of the paradoxical reaction (‘paradoxical pharmacology’), proposing the use of drugs that cause an exacerbation of the disease in the short term to treat these same diseases in the long-term. In this review, we compare the various aspects between the ‘homeopathic pharmacology’ and the ‘paradoxical pharmacology’, reinforcing the validity of homeopathic assumptions and expanding the knowledge to optimize both proposals.

Computerized interpretation of electrocardiogram plays an important role in daily cardiovascular healthcare. However, inaccurate interpretations lead to misdiagnoses and delay proper treatments. In this work, we built a high-quality Chinese 12-lead resting electrocardiogram dataset with 15,357 records, and called for a community effort to improve the performances of CIE through the China ECG AI Contest 2019. This dataset covers most types of ECG interpretations, including the normal type, 8 common abnormal types, and the other type which includes both uncommon abnormal and noise signals. Based on the Contest, we systematically assessed and analyzed a set of top-performing methods, most of which are deep neural networks, with both their commonalities and characteristics. This study establishes the benchmarks for computerized interpretation of 12-lead resting electrocardiogram and provides insights for the development of new methods. Graphical AbstractA community effort to assess and improve computerized interpretation of 12-lead resting electrocardiogram Supplementary information The online version contains supplementary material available at 10.1007/s11517-021-02420-z.

To analyze the circulating serum levels of the brain-derived neurotrophic factor (BDNF) in novice participants submitted to an extreme conditioning training session (ECT). Ten untrained male subjects were submitted to an ECT session, composed by the protocol "as many repetitions as possible" (WOD-AMRAP). The training session lasted 9 min, including the exercises clean, wall ball throw, and double or single-unders. At the end of the training session, Borg's perceived exertion assessment (RPE, 0–10) was assessed to demonstrate the level of physical requirement. Blood samples were collected baseline and immediately after the ECT session to measure BDNF. The Cohen's d effect size calculation was used to evaluate the magnitude of training effects on the BDNF levels. In addition, Pearson's correlation was applied between training parameters and BDNF acute delta response. The following results were found: (1) all individuals reported a similar level of effort ([RPE] 8.8 ± 0.78); (2) total training load and total volumes were 1456.4 ± 334.12 kg and 127 ± 28.2 repetitions, respectively; (3) the ratio between total load and the total volume was 11.45 ± 0.21 kg/repetition; (4) the mean BDNF response showed a significant increase (PRE 12,617 ± 2070 vs. POST 13,642 ± 1791 pg/mL, respectively) [ES = 0.49]; 5) no correlation was found between training parameters and BDNF delta acute responses. Through the results found here, we concluded that a high-density/effort WOD-AMRAP ECT session is able to stimulate the acute increase in serum BDNF levels in novice participants.

Background Hair cortisol concentration (HCC) has received attention as a useful marker of stress, but evidence on associations between psychological factors and cortisol concentration is inconsistent. The purpose of this study was to investigate the sex differences in the relationship between cortisol concentration and psychological factors in healthy young adults. Methods A total of 205 (103 females, 102 males) healthy young adults participated. HCC and various stress-related psychological measures were compared between sexes. Multiple linear regression analyses were performed to assess associations between HCC and stress-related psychological measures for all participants and for each sex. Results The difference in HCC according to sex was not significant. The reported number of stressful life events in the past year, stress perception, depressive and anxiety-related symptoms, and emotion dysregulation were not different between sexes, either. The association between HCC and emotion dysregulation was significant in females but not males. Conclusion We observed a sex-specific association between HCC and psychological factors. Our findings may imply that HCC could be a useful biomarker of stress and stress-related emotion dysregulation in healthy young women., Highlights Associations between hair cortisol level and psychological factors have been inconclusive.In healthy young adults, the hair cortisol concentration was not significantly different between sexes.The association between emotion dysregulation and hair cortisol was only found in women, but not in men.The role of sex should be considered in utilizing hair cortisol as a biomarker for psychological stress response.

Mechanical ventilation is a common invasive intervention in intensive care units. While respiratory failure remains the most common indication for mechanical ventilation, the application and indications of this intervention are far more variable. Ventilation causes marked alteration to human physiology and is associated with complications and iatrogenic injuries. This article highlights practical aspects of patient management during invasive ventilation.

Clusters’ behaviors can change with age, moving from adolescence to adulthood. This study examined physical activity (PA), diet, and sedentary behavior (SB) clusters according to age groups (11–12, 13–15, 16–17, and 18–19 years) and its association with sex and maternal education. Brazilian National School-based Health Survey (PeNSE 2015) (n = 16,522) data were analysed. Adolescents responded PA; consumption of fruits, vegetables; snacks, salt, and beverages (SSB); and SB. Two-step cluster analysis and Rao-Scott Chi square test were used. The Actives; the All-day sitters; the Inactive 1 (with moderate consumption of FV and the Inactive 2 (with small consumption of FV as against girls in All-day sitters, Inactive 1 and 2 clusters. The Actives had a higher proportion of adolescents with low maternal education. SB increase in clusters over the increase of age group; else, adolescents in Actives groups decreased.

Sportswear textile is the interface between consumers, clothing and the environment in conjunction with human physiology. In this study, multi-response optimization of sensorial comfort properties ...

This review article presents a collection of tool compounds that selectively block and are recommended for studying P2Y and P2X receptor subtypes, investigating their roles in physiology and validating them as future drug targets. Moreover, drug candidates and approved drugs for P2 receptors will be discussed.

Thiopurines (mercaptopurine, azathioprine and thioguanine) are well-established maintenance treatments for a wide range of diseases such as leukemia, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE) and other inflammatory and autoimmune diseases in general. Worldwide, millions of patients are treated with thiopurines. The use of thiopurines has been limited because of off-target effects such as myelotoxicity and hepatotoxicity. Therefore, seeking methods to enhance target-based thiopurine-based treatment is relevant, combined with pharmacogenetic testing. Controlled-release formulations for thiopurines have been clinically tested and have shown promising outcomes in inflammatory bowel disease. Latest developments in nano-formulations for thiopurines have shown encouraging pre-clinical results, but further research and development are needed. This review provides an overview of novel drug delivery strategies for thiopurines, reviewing modified release formulations and with a focus on nano-based formulations.

Infectious diseases present tremendous challenges to human progress and public health. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) pandemic continue to pose an imminent threat to humanity. These infectious diseases highlight the importance of developing innovative strategies to study disease pathogenesis and protect human health. Although conventional in vitro cell culture and animal models are useful in facilitating the development of effective therapeutics for infectious diseases, models that can accurately reflect human physiology and human-relevant responses to pathogens are still lacking. Microfluidic organs-on-a-chip (organ chips) are engineered microfluidic cell culture devices lined with living cells, which can resemble organ-level physiology with high fidelity by rebuilding tissue-tissue interfaces, mechanical cues, fluidic flow, and the biochemical cellular microenvironment. They present a unique opportunity to bridge the gap between in vitro experimental models and in vivo human pathophysiology and are thus a promising platform for disease studies and drug testing. In this Account, we first introduce how recent progress in organ chips has enabled the recreation of complex pathophysiological features of human infections in vitro. Next, we describe the progress made by our group in adopting organ chips and other microphysiological systems for the study of infectious diseases, including SARS-CoV-2 viral infections and intrauterine bacterial infections. Respiratory symptoms dominate the clinical manifestations of many COVID-19 patients, even involving the systemic injury of many distinct organs, such as the lung, the gastrointestinal tract, and so forth. We thus particularly highlight our recent efforts to explore how lung-on-a-chip and intestine-on-a-chip might be useful in addressing the ongoing viral pandemic of COVID-19 caused by SARS-CoV-2. These organ chips offer a potential platform for studying virus-host interactions and human-relevant responses as well as accelerating the development of effective therapeutics against COVID-19. Finally, we discuss opportunities and challenges in the development of next-generation organ chips, which are urgently needed for developing effective and affordable therapies to combat infectious diseases. We hope that this Account will promote awareness about in vitro organ microphysiological systems for modeling infections and stimulate joint efforts across multiple disciplines to understand emerging and re-emerging pandemic diseases and rapidly identify innovative interventions.

Microphysiological systems (MPS) or tissue chips/organs-on-chips are novel in vitro models that emulate human physiology at the most basic functional level. In this review, we discuss various hurdles to widespread adoption of MPS technology focusing on issues from multiple stakeholder sectors, e.g., academic MPS developers, commercial suppliers of platforms, the pharmaceutical and biotechnology industries, and regulatory organizations. Broad adoption of MPS technology has thus far been limited by a gap in translation between platform developers, end-users, regulatory agencies, and the pharmaceutical industry. In this brief review, we offer a perspective on the existing barriers and how end-users may help surmount these obstacles to achieve broader adoption of MPS technology.

Fasting has been demonstrated to improve health and slow aging in human and other species; however, its impact on the human body in the confined environment is still unclear. This work studies the effects of long-term fasting and confined environment on the cardiovascular activities of human via a 10-day fasting experiment with two groups of subjects being in confined (6 subjects) and unconfined (7 subjects) environments respectively and undergoing the same four-stage fasting/feeding process. It is found that the confinement has significant influences on the autonomic regulation to the heart rate during the fasting process by altering the activity of the parasympathetic nervous system, which is manifested by the significant higher pNN50, rMSSD, and Ln-HF of heart rate variability (HRV) (p

We aimed to evaluate whether genetically predicted HbA1c has an effect on the risk of cardiovascular diseases and investigate the shape of the relationship of genetically predicted HbA1c with cardiovascular diseases. We performed linear univariable, multivariable and non-linear Mendelian randomisation analyses in 373,571 white British participants (mean age 56.9) from the UK Biobank. In univariable linear Mendelian randomisation analysis, a 1 mmol/mol increase in genetically predicted HbA1c was associated with higher risk of coronary artery disease (OR 1.03, 95% CI 1.02, 1.05), stroke (OR 1.02, 95% CI 1.00, 1.05) and hypertension (OR 1.02, 95% CI 1.01, 1.03). Multivariable Mendelian randomisation adjusted for the effect of haemoglobin gave a consistent conclusion for coronary artery disease. The associations with stroke and hypertension were directionally similar but with wider CI overlapping the null. Non-linear Mendelian randomisation indicated that the shape of the effect of genetically predicted HbA1c on cardiovascular outcomes was likely linear. The study suggests a detrimental effect of HbA1c on coronary artery disease in both men and women, and the effect is via a glycaemic characteristic. The shape of the genetic association of HbA1c with these cardiovascular outcomes, in particular coronary artery disease, is likely to be linear.

There is an urgent need for models that faithfully replicate heart failure with preserved ejection fraction (HFpEF), now recognized as the most common form of heart failure in the world. In vitro approaches have several shortcomings, most notably the immature nature of stem cell‐derived human cardiomyocytes [induced pluripotent stem cells (iPSC)] and the relatively short lifespan of primary cardiomyocytes. Three‐dimensional ‘organoids’ incorporating mature iPSCs with other cell types such as endothelial cells and fibroblasts are a significant advance, but lack the complexity of true myocardium. Animal models can replicate many features of human HFpEF, and rodent models are the most common, and recent attempts to incorporate haemodynamic, metabolic, and ageing contributions are encouraging. Differences relating to species, physiology, heart rate, and heart size are major limitations for rodent models. Porcine models mitigate many of these shortcomings and approximate human physiology more closely, but cost and time considerations limit their potential for widespread use. Ex vivo analysis of failing hearts from animal models offer intriguing possibilities regarding cardiac substrate utilisation, but are ultimately subject to the same constrains as the animal models from which the hearts are obtained. Ex vivo approaches using human myocardial biopsies can uncover new insights into pathobiology leveraging myocardial energetics, substrate turnover, molecular changes, and systolic/diastolic function. In collaboration with a skilled cardiothoracic surgeon, left ventricular endomyocardial biopsies can be obtained at the time of valvular surgery in HFpEF patients. Critically, these tissues maintain their disease phenotype, preserving inter‐relationship of myocardial cells and extracellular matrix. This review highlights a novel approach, where ultra‐thin myocardial tissue slices from human HFpEF hearts can be used to assess changes in myocardial structure and function. We discuss current approaches to modelling HFpEF, describe in detail the novel tissue slice model, expand on exciting opportunities this model provides, and outline ways to improve this model further.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent worldwide. Recent clinical and experimental studies have addressed the association between cholecystectomy and MAFLD, confirming that cholecystectomy is an independent risk factor for MAFLD. In this review, we describe the epidemiologic evidence that links cholecystectomy to MAFLD, and discuss the possible mechanisms behind these connections, in order to unveil the metabolic and chronobiologic signals conveyed by the waves of the bile acid enterohepatic circulation.

Most dementia patients with a mixed dementia (MxD) diagnosis have a mix of Alzheimer’s disease (AD) and vascular dementia. Electrovestibulography (EVestG) records vestibuloacoustic afferent activity. We hypothesize EVestG recordings of AD and MxD patients are different. All patients were assessed with the Montreal cognitive assessment (MoCA) and Hachinski ischemic scale (HIS) (> 4 HIS score 80% for separating pairs of AD/MxD/control. Using the MoCA assessment and 2 EVestG features, a best accuracy of 81 to 91% depending on the classifier was obtained for the 3-way identification of AD, MxD and controls. EVestG measures provide a physiological basis for identifying AD from MxD. EVestG measures are hypothesized to be partly related to channelopathies and changes in the descending input to the vestibular periphery. Four of the five AD or MxD versus control features used had significant correlations with the MoCA. This supports assertions that the pathologic changes associated with AD impact the vestibular system and further are suggestive that the postulated physiological changes behind these features have an association with cognitive decline severity.

Bottled beer is used to calibrate a CO2 analyser by measuring the dilution of O2 when gas collected in the headspace of the bottle is diluted with atmospheric air. The method is simple and provides an accurate calibration of a CO2 analyser in the field without the need or hassle of transporting expensive calibration gas.

The purpose of this study is to investigate the Bottom–Up Rise Strength Transfer (BURST) induced by massed vs. distributed-rehabilitative exercise training. Participants were randomly allocated to one of the 12 weeks massed (MRT) vs. distributed-(DRT) rehabilitative exercise training (performing lower limb proprioceptive, balance, agility, and resistance exercise) group or no-intervention group (Control). The upper and lower limb strength assessment was recorded at baseline (pre), 8 weeks (mid), and 12 weeks (post). The net right hand MVC force increased after 12 weeks of DRT (58.3%). The net left hand MVC force increased after 12 weeks of both DRT and MRT (44.0% & 33.9% respectively). The BURST effect induced by DRT was significantly larger than MRT (in right hand: 45.1% & in left hand 33.4%). This is the first study investigating in a between-subject design the BURST effect of massed vs. distributed-rehabilitative training. The result showed middle-aged women can develop their upper limbs strength by performing both the DRT and MRT in their lower limbs. Lower body distributed resistance training, however, can provide a significantly greater stimulus for increasing the BURST in middle-aged women.

To investigate the association between frequency of physical activity (PA) and blood pressure values in the Brazilian population. A cross-sectional study of 25,920 males and 34,282 females was analyzed. Multiple linear regression was applied to test the association of different frequencies of PA and systolic and diastolic blood pressure. In the adjusted model, subjects who reported only one weekly session of moderate-intensity PA presented systolic blood pressure on average 2.5 mm (men: β = − 2.48 mmhg women: β = − 2.48 mmhg) lower than those inactive subjects. However, diastolic blood pressure showed significant results only among those who reported practicing three sessions or more of moderate (men: β = − 1.97 mmhg, women: β = − 2.65 mmhg) or vigorous intensity PA (men: β = − 0.96, women: β = − 1.79 mmhg). The results of the present study suggest that the low frequency of physical activity may have a similar protective effect, on resting systolic blood pressure, to that observed in individuals who have a weekly frequency equal to or greater than three weekly sessions.

The present study aimed to evaluate the morphological characteristics of the sphenoid sinus (SS), and the impact of potential influencing factors on the morphometric features using CBCT imaging. CBCT scans of 148 patients, aged between 15 and 85 (32.88 ± 15.33) years were retrospectively evaluated. DICOM files from the CBCT scans were imported into semi-automatic software and the SS of each patient was assessed for the morphological characteristics including configuration, symmetry, extension, shape, septation, volume, and maximum diameter. Furthermore, potential influencing factors such as age, gender, side, and sinus condition were analysed. A significant association was observed between sinus extension and age. Septation was also found to be significantly associated with age, gender and sinus condition. Besides, sinus volume was significantly associated with gender and sinus condition. No significant influence of shape and side on the morphometric features was noticed. The average volume and diameter of the SS were 6576.92 ± 3748.12 mm3 and 30.48 ± 9.28 mm, respectively. In conclusion, the present findings indicate that age, gender and sinus condition have a significant impact on the morphometric characteristics of the SS. Mature sinuses exhibit a post-sellar extension pattern until middle age. In addition, males, and sinuses with healthy sinus condition have larger volumes compared to females and pathological sinuses. ispartof: ANATOMICAL SCIENCE INTERNATIONAL vol:96 issue:4 pages:544-555 ispartof: location:Japan status: published

Funder: Wellcome Trust, PurposeSurgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice.MethodsA mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached.ResultsThere was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured.ConclusionsThrough an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed "core" steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The "optional" steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world.

The causal mechanisms and treatment for the negative symptoms and cognitive dysfunction in schizophrenia are the main issues attracting the attention of psychiatrists over the last decade. The first part of this review summarizes the pathogenesis of schizophrenia, especially the negative symptoms and cognitive dysfunction from the perspectives of genetics and epigenetics. The second part describes the novel medications and several advanced physical therapies (e.g., transcranial magnetic stimulation and transcranial direct current stimulation) for the negative symptoms and cognitive dysfunction that will optimize the therapeutic strategy for patients with schizophrenia in future.

Part II of the review considers the literature data that pronounced cardioprotective activity is possessed by sigma-1 receptors (σ1Rs) and is associated with both membranotropic and chaperone activities. Activated σ1Rs exert a distinct antiarrhythmic/antifibrillatory effect, display anti-ischemia activity, and prevent left ventricular hypertrophy and remodeling in pathological conditions. Oppositely, a blockage of the σ1Rs triggers malignant arrhythmias and provokes myocardial hypertrophy and remodeling.

To examine the temporal changes in blood oxidative stress biomarkers in recreationally-trained women that were naturally-cycling (WomenNC) or using oral contraceptives (WomenOC) across one month. Blood samples were acquired at three timepoints of the menstrual cycle (1: early-follicular, 2: late-follicular and 3: mid-luteal) and oral contraceptive packet (1: InactiveOC, 2: Mid-activeOC and 3: Late-activeOC) for determination of estradiol, progesterone, oxidative stress, C-reactive protein (CRP) and other cardiometabolic biomarkers in plasma and serum. There was a Group by Time effect on estradiol (p 0.05). At all timepoints (i.e., 1, 2 and 3), WomenOC had elevated lipid hydroperoxides (+ 28, + 48% and + 50%) and CRP (+ 71%, + 117% and + 130%) compared to WomenNC (p 0.25). There was no Group by Time effect on non-enzymatic antioxidants or glutathione peroxidase; however, glutathione peroxidase was lower in WomenOC, i.e., main effect of group (p 0.20). These findings demonstrate that WomenOC not only have higher oxidative stress and CRP than WomenNC, but also a transient increase across one month of habitual oral contraceptive use. Since changes in oxidative stress and CRP often relate to training stress and recovery, these outcomes may have implications to workload monitoring practices in female athletes.

Globally, the proportion of new diagnoses of youth-onset diabetes represented by type 2 diabetes is increasing, and youth with type 2 diabetes commonly have complications and comorbidities, as well as a higher rate of mortality. In this review, we summarise what is known about the natural progression of youth-onset type 2 diabetes from published clinical trials and large-scale prospective epidemiological studies. It is important to note that the robust pathophysiological and treatment data specifically related to individuals with a diabetes onset at ≤20 years of age largely hails from the USA. Youth-onset type 2 diabetes is characterised by pathophysiological heterogeneity and inadequate glycaemic control, highlighting the need for new treatment approaches and innovative study designs in populations of varied genetic and cultural backgrounds.

Aims/hypothesis Recurrent hypoglycaemia in people with diabetes leads to progressive suppression of counterregulatory hormonal responses to subsequent hypoglycaemia. Recently it has been proposed that the mechanism underpinning this is a form of adaptive memory referred to as habituation. To test this hypothesis, we use two different durations of cold exposure to examine whether rodents exposed to recurrent hypoglycaemia exhibit two characteristic features of habituation, namely stimulus generalisation and dishabituation. Methods In the first study (stimulus generalisation study), hyperinsulinaemic–hypoglycaemic (2.8 mmol/l) glucose clamps were performed in non-diabetic rodents exposed to prior moderate-duration cold (4°C for 3 h) or control conditions. In the second study (dishabituation study), rodents exposed to prior recurrent hypoglycaemia or saline (154 mmol/l NaCl) injections over 4 weeks underwent a longer-duration cold (4°C for 4.5 h) exposure followed 24 h later by a hyperinsulinaemic–hypoglycaemic (2.8 mmol/l) glucose clamp. Output measures were counterregulatory hormone responses during experimental hypoglycaemia. Results Moderate-duration cold exposure blunted the adrenaline (epinephrine) response (15,266 ± 1920 vs 7981 ± 1258 pmol/l, Control vs Cold; p p Conclusions/interpretation Non-diabetic rodents exhibit two cardinal features of habituation, namely stimulus generalisation and dishabituation. These findings provide further support for the hypothesis that suppressed counterregulatory responses following exposure to recurrent hypoglycaemia in diabetes result from habituation. Graphical abstract

The purpose of this meta-analysis was to evaluate the effects of acute exercise on short-term memory improvement. The computerized literature searches using electronic databases and examinations of reference lists from relevant studies yielded six studies meeting our inclusionary criteria. In a total of six studies, 16 standardized regression coefficient effect sizes (ESs) were calculated to be meta-analyzed. The meta-analyses showed a statistically significant increase in short-term memory improvement across both the exercise and non-exercise control groups in trials 1–5 [ES = 0.96, 95% CI (0.95, 0.97), P