Developing a long-term follow up service for bariatric surgical patients in the community: Patient and professional perspectives.
In the UK, bariatric surgical patients are followed up for 2 years post-operatively in hospital settings, before being discharged into General Practice for long-term follow-up. Presently, there is ambiguous guidance as to what should be included in a community-based bariatric surgical follow-up service. The aim of the study was to understand, from both patient and professional perspectives, what is needed to support the long-term management of bariatric surgical patients in community-based settings. Post-surgical bariatric patients and General Practice staff were recruited from an area in the UK which has an National Health Service (NHS) hospital providing a high-volume and established bariatric surgical service. Data was collected through semi-structured interviews. A thematic analytic framework was used to construct eight themes which illuminated the participants' experiences. The study took place between March and December 2021. Thirty participants (14 patients and 16 healthcare professionals) were recruited to the study. The study revealed the lack of a framework for delivery of a long-term follow up service was frustrating to both patients and professionals. Patient participants reported needing more support, especially dietetic and psychological input, and professionals stated they had little knowledge about bariatric surgical care, and what was needed to provide optimal care, but wanted to provide quality patient care. Long-term follow up of bariatric surgical patients is an important issue which needs addressing. This study illuminates both the patient and professional perspectives on developing a pragmatic, community-based service which meets the needs of patients and considers the need to incorporate such a service into existing infrastructures without adding additional demands on General Practice.


Demonstration of lever pressing for oral ethanol by rats with no prior training or ethanol experience.
Male rats of the alcohol-preferring AA line were placed in an operant conditioning chamber with one lever delivering 10% alcohol solution and a second giving water. Free food and water were also continually available in the chamber so the animals should not have been motivated to obtain alcohol for reasons of hunger or thirst. The rats had never had alcohol previously. No shaping was used. The rats simply lived for the next 2 weeks in the operant chamber. All of them eventually learned to work for alcohol. Ethanol responding was significantly higher than pressing for water throughout the second week: on the last day, all rats pressed more than 300 times for alcohol and less than 40 times for water, took in a mean of 5.3 +/- 0.2 g/kg of ethanol, and obtained 72% of their total fluid as earned ethanol solution despite the presence of free water. Their acquisition was, however, much slower than that observed in male AA rats that had previously had prolonged access to drinking alcohol in their home cages. Living continually in the operant chamber is thought probably to have been an important factor in enabling the naïve rats to learn to work for alcohol.


Intention to vaccinate against COVID-19 and adherence to non-pharmaceutical interventions against COVID-19 prior to the second wave of the pandemic in Uganda: a cross-sectional study.
The resurgence in cases and deaths due to COVID-19 in many countries suggests complacency in adhering to COVID-19 preventive guidelines. Vaccination, therefore, remains a key intervention in mitigating the impact of the COVID-19 pandemic. This study investigated the level of adherence to COVID-19 preventive measures and intention to receive the COVID-19 vaccine among Ugandans. A nationwide cross-sectional survey of 1053 Ugandan adults was conducted in March 2021 using telephone interviews. Participants reported on adherence to COVID-19 preventive measures and intention to be vaccinated with COVID-19 vaccines. Overall, 10.2% of the respondents adhered to the COVID-19 preventive guidelines and 57.8% stated definite intention to receive a SARS-CoV-2 vaccine. Compared with women, men were less likely to adhere to COVID-19 guidelines (Odds Ratio (OR)=0.64, 95% CI 0.41 to 0.99). Participants from the northern (4.0%, OR=0.28, 95% CI 0.12 to 0.92), western (5.1%, OR=0.30, 95% CI 0.14 to 0.65) and eastern regions (6.5%, OR=0.47, 95% CI 0.24 to 0.92), respectively, had lower odds of adhering to the COVID-19 guidelines than those from the central region (14.7%). A higher monthly income of ≥US$137 (OR=2.31, 95% CI 1.14 to 4.58) and a history of chronic disease (OR=1.81, 95% CI 1.14 to 2.86) were predictors of adherence. Concerns about the chances of getting COVID-19 in the future (Prevalence Ratio (PR)=1.26, 95% CI 1.06 to 1.48) and fear of severe COVID-19 infection (PR=1.20, 95% CI 1.04 to 1.38) were the strongest predictors for a definite intention, while concerns for side effects were negatively associated with vaccination intent (PR=0.75, 95% CI 0.68 to 0.83). Behaviour change programmes need to be strengthened to promote adherence to COVID-19 preventive guidelines as vaccination is rolled out as another preventive measure. Dissemination of accurate, safe and efficacious information about the vaccines is necessary to enhance vaccine uptake.


Idiopathic intracranial hypertension: Proposal of a stratification strategy for monitoring risk of disease progression.
A general consensus based on a multidisciplinary perspective involving an international panel was recently developed for management of patients with idiopathic intracranial hypertension (IIH). In this paper, the authors sought to develop further on the aspect of this consensus that concerns monitoring progression of the disease. A systematic literature review of previous publications on monitoring disease progression in IIH and a meta-analysis to examine efficacy of method of monitoring employed in each study. The authors present a brief descriptive analysis of challenges with monitoring progression of the disease and propose a risk stratification to aid monitoring. Of a total of 382 publications identified from the literature search, only 8 studies (144 patients) satisfied inclusion criteria and were included for analysis. Among these, 3 were based on ICP monitoring while the remaining 5 focused on ophthamological evaluation. Interestingly, there were neither any studies on monitoring with progression of clinical features nor any study on monitoring with symptomatology associated with IIH among the selected studies. There is a paucity of studies in the literature on methods of monitoring disease progression in IIH. Though close attention to adequate evaluation and proper care of patients with IIH remains the key in managing this problem, this proposed risk stratification will be an objective tool and useful guide to better monitor these patients according to their extent of risk from the disease and possibly for planning treatment and intervention.


Early dissemination of foot-and-mouth disease virus through sheep marketing in February 2001.
The results of epidemiological investigations suggest that livestock on up to 79 premises, spread widely throughout the British Isles, may have been exposed to infection by foot-and-mouth disease (FMD) virus by the movement of infected sheep before the first case of the disease was confirmed at an abattoir in Essex on February 20, 2001. A further 36 premises may have been infected by this route before the national livestock movement ban was imposed on February 23.


Systematic review reveals multiple sexually antagonistic polymorphisms affecting human disease and complex traits.
An evolutionary model for sex differences in disease risk posits that alleles conferring higher risk in one sex may be protective in the other. These sexually antagonistic (SA) alleles are predicted to be maintained at frequencies higher than expected under purifying selection against unconditionally deleterious alleles, but there are apparently no examples in humans. Discipline-specific terminology, rather than a genuine lack of such alleles, could explain this disparity. We undertook a two-stage review of evidence for SA polymorphisms in humans using search terms from (i) evolutionary biology and (ii) biomedicine. Although the first stage returned no eligible studies, the second revealed 51 genes with sex-opposite effects; 22 increased disease risk or severity in one sex but protected the other. Those with net positive effects occurred at higher frequencies. None were referred to as SA. Our review reveals significant communication barriers to fields as a result of discipline-specific terminology.


Vitreous fluorophotometry in adult-onset diabetes mellitus.
We studied the breakdown of the blood-retinal barrier in 83 patients with adult-onset diabetes mellitus, by using vitreous fluorophotometry. The patients were in good stable metabolic control and were receiving injectible insulin or oral hypoglycemic agents. Vitreous fluorophotometry readings were abnormally high but similar in both groups of patients, and no significant differences were found between those with and those without early background diabetic retinopathy. Significantly more patients taking oral agents were hypertensive, and significantly fewer of these patients had background retinopathy.


Association of continuity of carer and women's experiences of maternity care during the COVID-19 pandemic: A cross-sectional survey.
Recent research highlights the impact of the COVID-19 pandemic on maternity services, although none to date have analysed the association between continuity of carer and how women felt about the changes to pregnancy care and birth plans. To describe pregnant women's self-reported changes to their planned pregnancy care and associations between continuity of carer and how women feel about changes to their planned care. A cross-sectional online survey of pregnant women aged over 18 years in their final trimester of pregnancy in Australia. 1668 women completed the survey. Most women reported at least one change to pregnancy care and birthing plans. Women receiving full continuity of carer were more likely to rate the changes to care as neutral/positive (p<.001) when compared with women who received partial or no continuity. Pregnant women experienced many changes to their planned pregnancy and birth care during the COVID-19 pandemic. Women who received full continuity of carer experienced fewer changes to care and were more likely to feel neutral/positive about the changes than women who did not receive full continuity of carer.


Mycobacterium tuberculosis Joyrides Alveolar Macrophages into the Pulmonary Interstitium.
Alveolar macrophages reside in the airway lumen, where they are thought to remain. However, in this issue of Cell Host & Microbe,Cohen et al. (2018) show that Mycobacterium tuberculosis may induce their translocation into the lung interstitium, potentially acting as a Trojan horse for bacillary dissemination to other phagocytes.


Injuries of the thoracolumbar junction. Clinical and radiological results in 149 patients.
In a series of 149 fractures of the thoracolumbar junction (Th12-L1), treated at the Central Hospital of Tampere from 1968 to 1975, 101 patients were seen after an average interval of 5 years. Over half of the fractures were sustained at home or in leisure hours. Over 90% were anterior wedge fractures. One patient died in the hospital of other injuries. The injury caused peraplegia in three cases and other neurological lesions in six. The treatment was conservative except in the patients with paraplegia, who were surgically treated. The patients were mobilized after an average of 15 days. The neurological condition did not deteriorate. Noteworthy changes of the radiological findings occurred during follow-up. The clinical result was considered good in two thirds of the patients, and 91% were able to return to work. The frequency of neurological findings was significant in patients showing radiological deformities. The force responsible for the fracture correlated with the radiological findings and the occurrence of neurological lesions. Narrowing of the vertebral canal and degenerative changes observed on admission had a significant and unfavorable effect on the clinical result.


SERS-based antibiotic susceptibility testing: Towards point-of-care clinical diagnosis.
Emerging antibiotic resistant bacteria constitute one of the biggest threats to public health. Surface-enhanced Raman scattering (SERS) is highly promising for detecting such bacteria and for antibiotic susceptibility testing (AST). SERS is fast, non-destructive (can probe living cells) and it is technologically flexible (readily integrated with robotics and machine learning algorithms). However, in order to integrate into efficient point-of-care (PoC) devices and to effectively replace the current culture-based methods, it needs to overcome the challenges of reliability, cost and complexity. Recently, significant progress has been made with the emergence of both new questions and new promising directions of research and technological development. This article brings together insights from several representative SERS-based AST studies and approaches oriented towards clinical PoC biosensing. It aims to serve as a reference source that can guide progress towards PoC routines for identifying antibiotic resistant pathogens. In turn, such identification would help to trace the origin of sporadic infections, in order to prevent outbreaks and to design effective medical treatment and preventive procedures.


Lack of protection by oestrogen from radiation-induced testicular damage in the rat.
The influence of pretreatment with oestradiol dipropionate (E) on the response of the rat testis to radiation has been studied. Treatment of rats for 3 weeks with E (100 mg/kg per week) induced severe atrophy of the testis. At this time, the testes were locally irradiated to doses of 0, 4 or 15 Gy, E treatment was continued for a further week and the rats were killed 24 or 36 weeks later. Radiation alone had a marked effect on spermatogenesis as assessed by testicular weight and counts of regenerating tubule cross-sections. At 24 weeks, 8% of cross-sections were found to possess spermatogenic cells after 4 Gy and this had increased to 15% at 36 weeks. No significant regeneration was observed after 15 Gy. Similar results were obtained in those rats pretreated with E. Following irradiation alone, decreases in interstitial cell numbers and testicular luteinizing hormone (LH) receptors reflected Leydig cell damage. Again, pretreatment with oestrogen did not appear to reduce Leydig cell damage. The results of the present study suggest that pretreatment with oestrogen is not able to reduce the testicular damage induced by moderate to high single doses of radiation.


Rspo1/Rspo3-LGR4 signaling inhibits hepatic cholesterol synthesis through the AMPKα-SREBP2 pathway.
R-spondins (Rspos) are endogenous ligands of leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4). Rspos-LGR4 signaling plays important roles in embryogenesis, gastrointestinal homeostasis, and food intake. Here, we investigated the impacts of Rspos-LGR4 on hepatic cholesterol synthesis. Rspo1/3 and Lgr4 knockdown mice were used to investigate the impacts of Rspo1/3-LGR4 on hepatic cholesterol synthesis. AMPKα agonist, antagonist, and shRNA were used to explore the downstream targets of Rspos-LGR4 signaling. In our study, we reported that LGR4, Rspo1, and Rspo3 were highly expressed in hepatocytes and their expressions were sensitive to energy states. Rspo1 and Rspo3 reversed OA-induced cholesterol synthesis, accompanying with increased the phosphorylation of AMPKα Thr172, reduced SREBP2 nuclear translocation, and Srebf2 mRNA expression. Conversely, hepatic LGR4 knockdown increased hepatic cholesterol synthesis and decreased the phosphorylation of AMPKα both in vitro and in vivo. Activation or inhibition of AMPKα significantly abolished the effects of LGR4 deficiency or Rspos, respectively, on cholesterol synthesis. Knockdown of AMPKα1 or/and AMPKα2 repressed Rspos-induced inhibition on cholesterol synthesis. Our study indicates that Rspo1/Rspo3-LGR4 signaling in hepatocytes suppresses cholesterol synthesis via the AMPKα-SREBP2 pathway.


The history of the development of anabolic-androgenic steroids.
The history of anabolic-androgenic steroids (AASs) is an interesting tale that has its roots in ancient "endocrinology." More than 6000 years ago, farmers noted enhanced domestication of animals after castration. The development of AASs, and, later, their artificial synthesis, have remained a hot topic in scientific research and pharmaceuticals. Over the years, AASs have been used as a proposed treatment for a wide variety of ailments, despite deleterious side effects. Unfortunately, they have been, and still are, abused by body builders, athletes, and teens.


Rho Signaling in Dictyostelium discoideum.
Small GTPases of the Rho family are ubiquitous molecular switches involved in the regulation of most actin cytoskeleton dependent processes and many other processes not directly linked to actin. D. discoideum is a well-established model organism for studies of the actin cytoskeleton and its regulation by signal transduction pathways. D. discoideum is equipped with a complex repertoire of Rho signaling components, with 20 Rho GTPases, more than 100 regulators (including exchange factors, GTPase activating proteins and guanine nucleotide dissociation inhibitors), and nearly 80 effectors or components of effector complexes. In this review we examine the knowledge accumulated to date about proteins involved in Rho-regulated signaling pathways in D. discoideum, with an emphasis on functional studies. We integrate the information about individual components into defined signaling pathways, with a focus on three extensively investigated processes: chemotaxis, vesicle trafficking, and cytokinesis.


A comprehensive and longitudinal cardiac magnetic resonance imaging study of the impact of coronary ischemia duration on myocardial damage in a highly translatable animal model.
We performed a comprehensive assessment of the effect of myocardial ischemia duration on cardiac structural and functional parameters by serial cardiac magnetic resonance (CMR) and characterized the evolving scar. CMR follow-up on the cardiac impact of time of ischemia in a closed-chest animal model of myocardial infarction with human resemblance is missing. Pigs underwent MI induction by occlusion of the left anterior descending (LAD) coronary artery for 30, 60, 90 or 120 min and then revascularized. Serial CMR was performed on day 3 and day 42 post-MI. CMR measurements were also run in a sham-operated group. Cellular and molecular changes were investigated. On day 3, cardiac damage and function were similar in sham and pigs subjected to 30 min of ischemia. Cardiac damage (oedema and necrosis) significantly increased from 60 min onwards. Microvascular obstruction was extensively seen in animals with ≥90 min of ischemia and correlated with cardiac damage. A drop in global systolic function and wall motion of the jeopardized segments was seen in pigs subjected to ≥60 min of ischemia. On day 42, scar size and cardiac dysfunction followed the same pattern in the animals subjected to ≥60 min of ischemia. Adverse left ventricular remodelling (worsening of both LV volumes) was only present in animals subjected to 120 min of ischemia. Cardiac fibrosis, myocyte hypertrophy and vessel rarefaction were similar in the infarcted myocardium of pigs subjected to ≥60 min of ischemia. No changes were observed in the remote myocardium. Sixty-minute LAD coronary occlusion already induces cardiac structural and functional alterations with longer ischemic time (120 min) causing adverse LV remodelling.


FRA-1: A key factor regulating signal transduction of tumor cells and a potential target molecule for tumor therapy.
Fos-related antigen-1 (FRA-1) is a member of activator protein-1 (AP-1) transcription factor superfamily, and FRA-1 is highly expressed in colon cancer, breast cancer, gastric cancer, lung cancer, bladder cancer, and other tumors. The expression level of FRA-1 is closely related to the processes of tumor cell proliferation, apoptosis, transformation, migration, and invasion, which is a potential therapeutic target and prognostic factor for many tumors. Clarifying the detailed mechanism of action of FRA-1 could provide the theoretical basis for tumor diagnosis, treatment, and prognosis, and is of great significance for the study of tumor etiology and pathogenesis. In this paper, the expression levels and influencing factors of FRA-1 in various tumor tissues and cells are summarized, as well as the effect of FRA-1 expression level on the biological behavior of tumor cells and the signal transduction mechanism. At the same time, the signal transduction mechanism of FRA-1 in inflammation was expounded. In addition, the related metabolites, drugs and non-coding RNA that affect the expression and function of FRA-1 were summarized. Finally, it illustrates that FRA-1 may be taken as a key factor for tumor prognosis and a potential therapeutic target. This review provides a theoretical basis for the systematic understanding of the relationship between FRA-1 and tumors, its function, and possible mechanism.


World Experience in Immunization against Noncommunicable Diseases: Successes and Vectors for Further Development.
According to the World Health Organization, noncommunicable diseases (NCDs), also known as chronic diseases that do not spread from person to person, are one of the major burdens on public health and cause approximately 28 premature deaths worldwide every minute and close to 74% of deaths globally each year [...].


Quantitative sensory measures distinguish office workers with varying levels of neck pain and disability.
This study was undertaken to investigate any relationship between sensory features and neck pain in female office workers using quantitative sensory measures to better understand neck pain in this group. Office workers who used a visual display monitor for more than four hours per day with varying levels of neck pain and disability were eligible for inclusion. There were 85 participants categorized according to their scores on the neck disability index (NDI): 33 with no pain (NDI<8); 38 with mild levels of pain and disability (NDI 9-29); 14 with moderate levels of pain (NDI30). A fourth group of women without neck pain (n=22) who did not work formed the control group. Measures included: thermal pain thresholds over the posterior cervical spine; pressure pain thresholds over the posterior neck, trapezius, levator scapulae and tibialis anterior muscles, and the median nerve trunk; sensitivity to vibrotactile stimulus over areas of the hand innervated by the median, ulnar and radial nerves; sympathetic vasoconstrictor response. All tests were conducted bilaterally. ANCOVA models were used to determine group differences between the means for each sensory measure. Office workers with greater self-reported neck pain demonstrated hyperalgesia to thermal stimuli over the neck, hyperalgesia to pressure stimulation over several sites tested; hypoaesthesia to vibration stimulation but no changes in the sympathetic vasoconstrictor response. There is evidence of multiple peripheral nerve dysfunction with widespread sensitivity most likely due to altered central nociceptive processing initiated and sustained by nociceptive input from the periphery.


Marital Transition and Risk of Stroke: How Living Arrangement and Employment Status Modify Associations.
There have been consistent findings reported that marital transition (ie, change in marital status during a given time period) is associated with risk of cardiovascular disease; however, few studies have been conducted on stroke risk, particularly stroke subtypes. Moreover, no studies have examined the moderating effect of living arrangement and employment status on the association between marital transition and stroke risk. We examined sex-specific associations between marital transition and stroke risk using data from Japan Public Health Center-based Prospective Study. We included 24 162 men and 25 626 women who were married at prebaseline (5 years before baseline). Marital transition was determined by marital status at baseline. Weighted hazard ratios of stroke risk were estimated by Cox proportional regression analysis with inverse probability of weighting using a propensity score. An increased risk of stroke, particularly hemorrhagic stroke, was observed among men and women with marital transition (ie, married to unmarried); weighted hazard ratios (95% confidence interval [CI]) for men and women were 1.26 (1.13-1.41) and 1.26 (1.09-1.45), respectively. Participants with marital transition and lived with children had increased stroke risk. Living with parents buffered the increased stroke risk owing to marital transition among men; however, no such effect was identified among women. Elevated stroke risk owing to marital transition was magnified among women if they were unemployed; weighted hazard ratio=2.98 (95% CI, 1.66-5.33). Living arrangement and employment status modified the positive associations between marital transition and stroke risk, which differed by sex.


Quantitative SPECT (QSPECT) at high count rates with contemporary SPECT/CT systems.
Accurate QSPECT is crucial in dosimetry-based, personalized radiopharmaceutical therapy with 177Lu and other radionuclides. We compared the quantitative performance of three NaI(Tl)-crystal SPECT/CT systems equipped with low-energy high-resolution collimators from two vendors (Siemens Symbia T6; GE Discovery 670 and NM/CT 870 DR). Using up to 14 GBq of 99mTc in planar mode, we determined the calibration factor and dead-time constant under the assumption that these systems have a paralyzable behaviour. We monitored their response when one or both detectors were activated. QSPECT capability was validated by SPECT/CT imaging of a customized NEMA phantom containing up to 17 GBq of 99mTc. Acquisitions were reconstructed with a third-party ordered subset expectation maximization algorithm. The Siemens system had a higher calibration factor (100.0 cps/MBq) and a lower dead-time constant (0.49 μs) than those from GE (75.4-87.5 cps/MBq; 1.74 μs). Activities of up to 3.3 vs. 2.3-2.7 GBq, respectively, were quantifiable by QSPECT before the observed count rate plateaued or decreased. When used in single-detector mode, the QSPECT capability of the former system increased to 5.1 GBq, whereas that of the latter two systems remained independent of the detectors activation mode. Despite similar hardware, SPECT/CT systems' response can significantly differ at high count rate, which impacts their QSPECT capability in a post-therapeutic setting.


Esophageal Eosinophilia Is Common Among Relatives of Eosinophilic Esophagitis Patients.
Familial clustering of eosinophilic esophagitis (EoE) has been described, and we report on the biopsy-assessed prevalence of esophageal eosinophilia (EE) in first-degree family members. The aim was to determine the prevalence of EE in first-degree adult relatives (FDRs) of EoE patients. Index EoE patients diagnosed by EE (>15 eosinophils per high-power field) and proton pump inhibitor nonresponsiveness were identified and family trees were constructed. Adult FDRs were invited to undergo upper endoscopy with esophageal biopsies and to complete reflux, dysphagia, and allergy/atopy questionnaires. Questionnaire information was gathered only for those who responded as per institutional review board purview. Records from other children and adult FDRs with prior EoE diagnoses also were obtained when permission was obtained. Simple and multivariable logistic regression models were used to evaluate the unadjusted and odds ratios of EoE for demographic and clinical variables. A total of 239 FDRs from 37 index EoE patients were identified. Seventy-one of 239 adult (age, >18 y) FDRs completed endoscopy and questionnaires and 18 of 71 FDRs had EE. An additional 17 FDRs were confirmed to have EE after external medical record retrieval, resulting in a total of 35 of 239 (14.6%) FDRs with EE. Significantly more male FDRs had EE compared with female FDRs (P = .027). Proton pump inhibitors, dysphagia, gastroesophageal reflux disease, asthma, and reflux symptoms predicted EE in FDRs. FDRs who had EE reported hay fever, allergic eye symptoms, and food allergy more frequently than those without EE (P = .03, P = .001, and P = .02, respectively). Specifically, younger age, higher serum eosinophils, being male, and having food allergies all were associated with higher odds of EoE (P = .0211, P = .0031, P = .0362, and P = .0089, respectively). The prevalence of esophageal eosinophilia is extremely high and male-predominant in first-degree relatives of EoE patients. Symptoms of hay fever, allergic eye symptoms, and food allergy were predictors of EE in FDRs. Dysphagia did not predict esophageal eosinophilia. Family members of EoE patients are at risk for EE, particularly those who have atopic symptoms.


At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy.
Tumors can avoid immune surveillance by stimulating immune inhibitory receptors that function to turn off established immune responses. By blocking the ability of tumors to stimulate inhibitory receptors on T cells, sustained, anti-tumor immune responses can be generated in animals. Thus, therapeutic blockade of immune inhibitory checkpoints provides a potential method to boost anti-tumor immunity. The CTLA-4 and PD-1Rs represent two T cell-inhibitory receptors with independent mechanisms of action. Preclinical investigations revealed that CTLA-4 enforces an activation threshold and attenuates proliferation of tumor-specific T lymphocytes. In contrast, PD-1 functions primarily as a stop signal that limits T cell effector function within a tumor. The unique mechanisms and sites of action of CTLA-4 and PD-1 suggest that although blockade of either has the potential to promote anti-tumor immune responses, combined blockade of both might offer even more potent anti-tumor activity. See related review At the Bedside: CTLA-4 and PD-1 blocking antibodies in cancer immunotherapy.


Link between the referring physician and breast and cervical cancers screening: a cross-sectional study in France.
The aims of the "médecin traitant" or referring physician (RP) reform, introduced in France in 2004, were to improve the organisation and quality of care and to allow for greater equity, particularly in terms of prevention. The objective of our study was to evaluate the effect of having a declared RP on the uptake of screening for breast and cervical cancers, and to explore the mechanisms involved. We used an existing dataset of 1,072,289 women, which combines data from the Health Insurance information systems, with census data. We built multivariable logistic regression models to study the effect of having a RP on the uptake of mammography and pap smear, adjusted for age, socio-economic level, health status and healthcare provision. We secondarily added to this model the variable "having consulted a General Practitioner (GP) within the year". Finally, we evaluated the interaction between the effect of having a referring physician and the area of residence (metropolitan/urban/rural). Patients who had a declared RP had a significantly higher uptake of mammography and pap smear than those who did not. The strength of the association was particularly important in very urban areas. The effect of having visited a GP seemed to explain a part of the correlation between having a RP and uptake of screening. Lower rates of gynaecological screening among women without an RP compared to those with an RP may partly reflect a specific behaviour pattern in women less adherent to the health care system. However, this result also shows the importance of the RP, who assumes the key role of relaying public health information in a more personalised and adapted way.


Lipid levels in obese and nonobese subjects as predictors of fasting and postload glucose metabolism.
Dyslipidemia in the overweight/obese patient often is associated with impaired glucose metabolism. The authors of large clinical trials in different ethnic groups highlighted the correlation between glycemia and lipid profile, although the effect of abdominal adiposity was not explored. To evaluate the relationship of visceral adiposity and lipid profile with fasting (FPG) and postload glucose (2hPG) in subjects without known diabetes (DM2). A total of 3030 subjects were divided in three groups: obese subjects (OB; n = 490), nonobese subjects with an increased waist circumference (NOB/W+; n = 500), and nonobese subjects without an increased waist circumference (NOB/W-; n = 2040). We performed a linear regression analysis among lipid fractions and fasting and 2hPG in the three groups, with or without diagnosis of DM2 after 2hPG. Our data confirmed the significant association (P < .01) of high triglycerides and low high-density lipoprotein cholesterol (HDL-C) with fasting and 2hPG in all three groups such as for non-HDL cholesterol, whereas total cholesterol (TC) showed a significant correlation only with fasting glucose in OB and NOB/W+ subjects (P < .01). The analysis with or without DM2 demonstrated no difference in the statistical significance, although a better correlation in subjects without DM2 was observed. In addition, for each quartile of TC a significant trend (P < .01) in prevalence of fasting hyperglycemia in obese and in NOB/W+ patients was observed. This study suggests that triglycerides and HDL-C, together with non-HDL cholesterol, are associated with impaired fasting and 2hPG and that high total cholesterol levels are associated with abnormalities of fasting glucose metabolism only in patients with elevated waist circumference.


[Chronic inflammatory bowel diseases competence network ].
Inflammatory bowel diseases (IBD) are intermittently appearing, often chronic diseases mostly affecting young people between 20-30 years of age influencing their quality of life and socioeconomic efficiency. The triggering factors for the development of IBD are not completely understood: besides environmental factors there is clear evidence for additional genetic factors influencing the risk of disease and the pattern of gut inflammation in Crohn's disease. Pathopysiological discoveries are leading to new therapeutic opportunities which are conducted in large clinical studies with main participation of the competence network IBD. The disseminated structure of the network comprising universitary and nonuniversitary hospitals and labs, the self-help-organization DCCV and its vertical cooperation with general practitioners nationwide gives opportunity to describe the diseases from the point of view of the scientist and the physician simultaneously. Therefore the competence network IBD yields the basis for the standardized integration of patient information, for the development of guidelines and the establishment of a quality management system thus leading to an improvement of scientific and clinical research.


Endotoxin concentrations within the breathing zone of horses are higher in stables than on pasture.
Inflammatory airway disease is common in stabled horses, with a prevalence of 17.3% in Michigan pleasure horses. Stable dust is rich in endotoxin, which may induce neutrophilic airway inflammation. Climatological conditions (ambient temperature and relative humidity) may influence endotoxin concentrations in pastures. The aim of this project was to determine if endotoxin levels in the breathing zone of horses in stables were higher than of horses on pasture, and if the endotoxin on pasture was associated with climatological conditions. Endotoxin exposure of six horses that were stabled or on pasture was determined by a Limulus amebocyte lysate assay. Climatological data were obtained from the US National Climatic Data Center. Endotoxin exposure was significantly higher (about 8-fold) in stables than on pasture. On pasture, endotoxin varied widely, despite constant climatological conditions. It was concluded that stabled horses are exposed to higher endotoxin concentrations than horses on pastures. Local endotoxin concentrations may be more important than ambient climatological conditions in determining endotoxin exposure of individual horses.


Sources of variation in the assimilation of lead by a common gastropod sentinel Cantareus aspersus.
The assimilation efficiency of Pb was measured in the candidate sentinel Cantareus aspersus, to assess its capacity to consistently represent the bioavailability of Pb. Three populations were compared from habitats with different levels of toxic and essential metals. For each, 36 snails were fed a laboratory diet with known concentrations of Pb, Ca and Mg over 64 days. Lead bioavailability was measured as the percentage assimilation by the soft tissues (mass in tissues as a fraction of that consumed), and its variation was assessed between populations, exposure periods, dietary Mg and replicates. The indicated bioavailability was consistent over time and Pb consumed, but differed between populations and diets. Population differences were due, in part, to their different growth rates: soft tissue growth was positively correlated with Pb mass and, in the most rapidly growing populations, this accounted for more than 40% of the variation in soft tissue Pb. Populations did not differ in their consumption of Pb, but the highest Mg diet induced higher food consumption and a reduced assimilation of Pb. Tissue growth determines retention and contributes to the variation in the bioavailability indicated by these populations, as do essential metals in the diet. Such variability has important implications for monitoring programmes using resident populations of sentinels to map the bioavailability of toxic metals or integrate a pollution signal over time.


[Pilot experience with implantations of 100 continuous atrial pacemakers in sick sinus syndrome: advances, problems, prospects].
Long-term results of continuous atrial pacing were assessed in 100 patients with sick sinus syndrome followed up for 6 years. Implantation of the pacemaker was performed via extrapleural and extraperitoneal approaches using serial myocardial non-suture electrodes. Antiarrhythmic efficacy of atrial pacing was found insufficient. Continuous atrial pacing proved advantageous only in Wenckebach point at 100-120 per min.


Three-Dimensional-Coordination Polymer of Zn(II)-Carboxylate: Structural Elucidation, Photoelectrical Conductivity, and Biological Activity.
A newly designed mixed-ligand coordination polymer [Zn4(bdc)4(ppmh)2(H2O)] n (1) (H2 bdc = 1,4-benzene dicarboxylic acid, ppmh = N-pyridin-2-yl-N'-pyridin-4-ylmethylene-hydrazine) has been characterized using different physicochemical techniques. The structure has been confirmed by single crystal X-ray diffraction measurements. There are two pyridyl-N and one hydrazino-imine-N donor centers in ppmh, where two pyridyl-Ns bind simultaneously to two Zn(II) to serve as a bridging agent to form a coordination polymer. The 1,4-benzene dicarboxylato (bdc) is ligated via the aromatic dicarboxylato-O to form a one-dimensional (1D) chain. These two 1D chains about Zn(II) constitute a two-dimensional structure, which undergoes noncovalent interactions (C-H···π and π···π) to generate a three-dimensional supramolecular assembly. Electrical conductivity of 1 is higher by 1 order (1.37 × 10-6 S/cm) than that of the free ligand, ppmh (6.2 × 10-7 S/cm). Especially, the responsivity of the compound 1 was 56.21 mA/W, which is 11 times higher than that of the ligand ppmh (5.12 mA/W). The specific detectivity of the compound was 2.17 × 1010 Jones, which is also almost 10 times higher with respect to the specific detectivity of the ligand-based device (4.53 × 109 Jones). The results show that the compound can be valuable for optoelectronic fields. The biological studies suggest that compound 1 is antibacterial as well as a promising anticancer agent (LD50, 42.2 μg/mL against HepG2 cells), while ligands remain silent. Investigation of the mechanism of the cell killing activity of compound 1 accounts the generation of intracellular reactive oxygen species.


Microscale syntheses of anti-tumour platinum compounds labelled with 191Pt.
Several compounds of platinum have been found to have significant anti-tumour activity and are in various stages of clinical trials. Four such compounds: cis-PtCl2(NH3)2, cis PtCl2(cyclopropylamine)2, cis,trans-PtCl2(OH)2(isopropylamine)2 and cis-Pt(1,1-cyclobutanedicarboxylate) (NH3)2 were synthesised with radioactive platinum-191 as a label for the study of animal organ distribution, patient blood clearance, urinary excretion and renal uptake and clearance. This paper describes the microscale synthesis of these compounds. Purification and quality control procedures are also described.


Suspected Giant Cell Aortitis: From Multiple Aortic Structural Damage to Fatal Listeria Sepsis, a Case Report.
Giant cell arteritis (GCA) is an inflammatory vasculopathy affecting large- and middle-sized vessels, specifically cranial arteries derived from carotid artery. Isolated extracranial vessel involvement can occur. Interest in extravascular manifestations is recently increasing because of diffusion of sensitive and specific imaging tools such as fluorodeoxyglucose positron emission tomography computerized tomography (18 FDG PET CT). Patients have an increased relative risk of severe infection. Listeria monocytogenes infection risk is increased, and vascular system involvement and graft infection have been, although rarely, reported. We report the case of a 72-year-old woman with a history of suspected giant cell aortitis, previous surgical treatment of ascendant and descendant thoracic aortic aneurysm, presenting 7 years after thoracic endovascular aneurysm repair with thoracic pain, fever, inflammatory indexes increase, leukocytosis, Listeria sepsis, and rapidly increasing type I proximal endoleak on CT. 18 FDG PET positivity was associated. Endograft listeria infection on aortitis reactivation was suspected, but death for multiorgan failure and absence of autopsy data could not confirm diagnosis. Listeria vascular graft infection has been reported previously. GCA is a predisposing condition. We report the first case of endograft infection by L monocytogenes in a patient with a positive history of suspected giant cell aortic aneurysm.


Bacteria-killing ability of fresh blood plasma compared to frozen blood plasma.
In recent years, the bacteria-killing assay (BKA) has become a popular technique among ecoimmunologists. New variations of that assay allow researchers to use smaller volumes of blood, an important consideration for those working on small-bodied animals. However, this version of the assay requires access to a lab with a nanodrop spectrophotometer, something that may not be available in the field. One possible solution is to freeze plasma for transport; however, this assumes that frozen plasma samples will give comparable results to fresh ones. We tested this assumption using plasma samples from three species of birds: chickens (Gallus gallus), ash-throated flycatchers (Myiarchus cinerascens), and western bluebirds (Sialia mexicana). Chicken plasma samples lost most or all of their bacterial killing ability after freezing. This did not happen in flycatchers and bluebirds; however, frozen plasma did not produce results comparable to those obtained using fresh plasma. We caution researchers using the BKA to use fresh samples whenever possible, and to validate the use of frozen samples on a species-by-species basis.


Results from Estonia's 2022 Report Card on Physical Activity for Children and Youth: Research Gaps and Five Key Messages and Actions to Follow.
The aim of this article is to summarize the results of the 2022 Estonian Physical Activity Report Card across 10 indicators based on available scientific data and national databases, and, additionally, to compare the current results with previous Report Card results. A national expert panel, consisting of research and policy experts, identified the available sources and synthesized as well as graded relevant data related to the physical activity (PA) of Estonian children and youth. Grade B was assigned to Organized Sports and Physical Activity (B-), Community and Environment (B+), and Government (B). Grade C was assigned to Overall Physical Activity (C+), Physical Fitness (C+), Family and Peers (C-), and School (C+). The lowest grade, D, was assigned to Active Play (D), Active Transportation (D+), and Sedentary Behaviors (D-). In Estonia, the participation rate in organized sport is relatively high, and government in addition to community support seem to be at a relatively good level. However, a relatively high number of children and youth did not meet the current PA guidelines, and the levels of sedentary behavior and screen time were very high. The PA of children and youth should be a cross-disciplinary priority, and focus should be put on developing schoolyards and outdoor breaks, varied and easily accessible organized sport, the use of active transportation, and the implementation of physical education that supports leisure time activities.


Prevention of assay interference in infectious-disease serology tests done on the liaison platform.
Immunoassay interference causing unexpected reactive results in magnetic-microparticle-based assays was detected. A systematic evaluation of Liaison Epstein-Barr virus immunoglobulin M showed that 5% of the positive results (0.4% of tested samples) could be explained by such interference. Adding chemical blocking reagents (polyvinylpyrrolidone and polyvinyl alcohol) to the assay buffers partially prevented this phenomenon.


C. elegans neuroscience: genetics to genome.
From their earliest experiments, researchers using Caenorhabditis elegans have been interested in the role of genes in the development and function of the nervous system. As the C. elegans Genome Project completes the genomic sequence, we review the accomplishments of these researchers and the impact that the Genome Project has bad on their research. We also speculate on future directions in this research that are enabled by the efforts of the Genome Project.


A marker-free method to estimate joint centre of rotation by video image processing.
A marker-free video measurement and image processing method that provides numerical estimation of the 2-D centre of rotation of one rigid segment is tested. The algorithm is based on binary region moment features. A comparison is made between this method and a marker-based one, where the location of the markers has been calculated in two ways. The algorithm is also extended to handle two rigid segments. The method is to be applied in human locomotion analysis in order to calculate the centre of rotation of the hip joint. It's accuracy has been tested by a comparison with in vivo radiological measurements on humans.


Wedge Hemivertebra Forward-Shifting Technique for Treatment of Congenital Kyphosis: Case Report, Technical Note, and Literature Review.
Congenital kyphosis due to wedge hemivertebra is an uncommon spinal deformity that could progressively develop into sagittal imbalance accompanied by subsequent neurologic deterioration if no intervention is performed. Numerous surgical techniques have been reported, since congenital kyphosis has shown no response to conservative treatments. Currently, osteotomy procedures, which are considered technically demanding and risky, have become the mainstream techniques for the correction of congenital kyphosis. We describe the use of a novel surgical procedure combining forward-shifting of anterior column of the wedge hemivertebra and circumferential fusion for treatment of congenital kyphosis secondary to a wedge hemivertebra in a case of a 13-year-old boy who showed a 49° angular kyphosis from T12 to L2 secondary to a wedge hemivertebra in L1. The focal kyphosis was corrected to 5° with a correction rate of 89.8% after operation, and the sagittal balance was significantly preserved with no complication. Solid fusion was detected at the final follow-up. This novel procedure, combining forward-shifting of anterior column of the wedge hemivertebra and circumferential fusion, is a feasible, effective, and safe technique for the treatment of some special type 1 congenital kyphosis cases, with a high correction rate and no major complications.


Did expansion of insurance coverage for major diseases in Korea induce a positive spillover effect on dental service utilization?
Although people with serious major diseases are disproportionately likely to have poor oral health, they are also more likely to defer treatment for oral health conditions due to financial constraints. The South Korean government introduced a comprehensive benefit expansion policy covering four major disease categories in 2013: cancer, cardiac diseases, cerebrovascular diseases, and rare diseases. Meanwhile, a policy expanding benefits for dental prosthetic services for the elderly was also introduced during the same period. Using nationally representative Korean Health Panel data from 2012 to 2017, we performed a difference-in-difference (DID) analysis to examine the positive spillover effect of insurance expansion for the four major disease categories on encouraging dental service utilization (frequency of dental visits and dental out-of-pocket payments) or decreasing unmet dental needs. Additionally, a triple-difference (TD) analysis was performed to examine whether the effect of coverage expansion of dental prosthetic services on dental service utilization was larger among the beneficiaries of the expansion for the four major disease categories. Benefit expansion for the four major disease categories did not significantly affect dental service utilization among the beneficiaries (DID model) during all study years and slightly increased unmet dental needs in 2014 and 2015. However, the effect of expanded coverage for dental prosthetic services on encouraging dental service utilization was larger (TD model) among the beneficiaries of the policy for the four major disease categories than among non-beneficiaries when we defined the beneficiaries as individuals with two or more household members who had one of the four major diseases. Our results suggest a need to provide more intense coverage for those with comorbidities by embracing the concept of proportionate universalism in the coverage of dental services.


Association of serum gamma-glutamyl transferase with myosteatosis assessed by muscle quality mapping using abdominal computed tomography.
Myosteatosis, which is associated with a variety of cardiometabolic illnesses, represents muscle quality, an important aspect of sarcopenia. A new laboratory marker for myosteatosis has been required to more readily identify it. We investigated whether serum gamma-glutamyl transferase (GGT) levels are associated with myosteatosis measured by computed tomography (CT). The total abdominal muscle area (TAMA) of 13,452 subjects was measured at the L3 level with abdominal CT. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, LAMA/BMI, and NAMA/TAMA. Logistic regression analysis was used to examine the odds ratio (OR) of each GGT quartile for the highest quartile of myosteatosis indices in each sex. The mean age and serum GGT levels were 53.7 years and 32.8 IU/L (standard deviation [SD], 37.6), respectively, in men, and 53.2 years and 18.4 IU/L (SD, 19.8) in women. In both sexes, the ORs of all myosteatosis indices differed significantly between GGT quartiles. Indices of good- and poor-quality muscle were negatively and positively correlated with GGT levels, respectively. Higher GGT levels were significantly associated with advanced myosteatosis defined by reliable CT indices. This result opens the possibility for using GGT as a cost-effective indicator of myosteatosis. Further prospective research on changes to GGT levels with myosteatosis alleviation will validate GGT as a monitoring marker.


Activation of glycogenolysis by methotrexate. Influence of calcium and inhibitors of hormone action.
The influence of Ca2+ and the possible action of hormone blockers on the activation of glycogenolysis by methotrexate were investigated. Methotrexate was inactive on glycogenolysis and oxygen uptake when the liver, depleted of intracellular Ca2+, was perfused with Ca(2+)-free medium. The action of methotrexate in calcium-depleted hepatocytes could be restored by the addition of extracellular Ca2+. When Ca2+ was absent in the extracellular medium, but the intracellular stores were not depleted, methotrexate produced transient and progressively attenuated increases in glycogenolysis and oxygen uptake. Like many agonists, methotrexate produced transient increases in Ca2+ efflux. The action of methotrexate was not blocked by the antagonists of norepinephrine, phenylephrine, isoproterenol, vasopressin and angiotensin II. It was concluded that methotrexate acts through a Ca(2+)-dependent mechanism, which is similar to that of the Ca(2+)-dependent agonists. This action, however, seems not to be receptor mediated.


Awareness and knowledge about human papillomavirus vaccination and its acceptance in China: a meta-analysis of 58 observational studies.
The human papillomavirus (HPV) vaccines have been widely introduced in immunization programs worldwide, however, it is not accepted in mainland China. We aimed to investigate the awareness and knowledge about HPV vaccines and explore the acceptability of vaccination among the Chinese population. A meta-analysis was conducted across two English (PubMed, EMBASE) and three Chinese (China National Knowledge Infrastructure, Wan Fang Database and VIP Database for Chinese Technical Periodicals) electronic databases in order to identify HPV vaccination studies conducted in mainland China. We conducted and reported the analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty-eight unique studies representing 19 provinces and municipalities in mainland China were assessed. The pooled awareness and knowledge rates about HPV vaccination were 15.95 % (95 % CI: 12.87-19.29, I (2) = 98.9 %) and 17.55 % (95 % CI: 12.38-24.88, I (2) = 99.8 %), respectively. The female population (17.39 %; 95 % CI: 13.06-22.20, I (2) = 98.8 %) and mixed population (18.55 %; 95 % CI: 14.14-23.42, I (2) = 98.8 %) exhibited higher HPV vaccine awareness than the male population (1.82 %; 95 % CI: 0.50-11.20, I (2) = 98.5 %). Populations of mixed ethnicity had lower HPV vaccine awareness (9.61 %; 95 % CI: 5.95-14.03, I (2) = 99.0 %) than the Han population (20.17 %; 95 % CI: 16.42-24.20, I (2) = 98.3 %). Among different regions, the HPV vaccine awareness was higher in EDA (17.57 %; 95 % CI: 13.36-22.21, I (2) = 98.0 %) and CLDA (17.78 %; 95 % CI: 12.18-24.19, I (2) = 97.6 %) than in WUDA (1.80 %; 95 % CI: 0.02-6.33, I (2) = 98.9 %). Furthermore, 67.25 % (95 % CI: 58.75-75.21, I (2) = 99.8 %) of participants were willing to be vaccinated, while this number was lower for their daughters (60.32 %; 95 % CI: 51.25-69.04, I (2) = 99.2 %). The general adult population (64.72 %; 95 % CI: 55.57-73.36, I (2) = 99.2 %) was more willing to vaccinate their daughters than the parent population (33.78 %; 95 % CI: 26.26-41.74, I (2) = 88.3 %). Safety (50.46 %; 95 % CI: 40.00-60.89, I (2) = 96.6 %) was the main concern about vaccination among the adult population whereas the safety and efficacy (68.19 %; 95 % CI: 53.13-81.52, I (2) = 98.6 %) were the main concerns for unwillingness to vaccinate their daughters. Low HPV vaccine awareness and knowledge was observed among the Chinese population. HPV vaccine awareness differed across sexes, ethnicities, and regions. Given the limited quality and number of studies included, further research with improved study designis necessary.


Global Gene Expression Analysis in PKCα-/- Mouse Skin Reveals Structural Changes in the Dermis and Defective Wound Granulation Tissue.
The skin's mechanical integrity is maintained by an organized and robust dermal extracellular matrix (ECM). Resistance to mechanical disruption hinges primarily on homeostasis of the dermal collagen fibril architecture, which is regulated, at least in part, by members of the small leucine-rich proteoglycan (SLRP) family. Here we present data linking protein kinase C alpha (PKCα) to the regulated expression of multiple ECM components including SLRPs. Global microarray profiling reveals deficiencies in ECM gene expression in PKCα-/- skin correlating with abnormal collagen fibril morphology, disorganized dermal architecture, and reduced skin strength. Detailed analysis of the skin and wounds from wild-type and PKCα-/- mice reveals a failure to upregulate collagen and other ECM components in response to injury, resulting in delayed granulation tissue deposition in PKCα-/- wounds. Thus, our data reveal a previously unappreciated role for PKCα in the regulation of ECM structure and deposition during skin wound healing.


Further examination of the production-line hypothesis in mouse foetal oocytes. II. T(14; 15)6Ca heterozygotes.
Pachytene oocytes from foetal mice heterozygous for the translocation T(14; 15)6Ca were screened for evidence of a "production-line" effect on chromosome pairing. Metaphase I oocytes from adult heterozygotes were also examined to determine whether any such effect on pahytene chromosome pairing is subsequently repeated during adult reproductive life as anticipated by the production-line hypothesis. It was found that as gestation proceeded the proportion of pachytene oocytes with a translocation quadrivalent declined and that with a trivalent and univalent correspondingly increased. That is, there was evidence of variation in pairing behaviour of the translocation at different times of gestation. In contrast, the proportions of metaphase I cells with either a quadrivalent or a trivalent plus univalent did not vary between adult females of different ages. Thus if the variation observed at pachytene was the result of a production-line effect, clearly this was not reflected in the behaviour of the translocation at metaphase I. Our observations therefore do not support the production-line hypothesis for the maternal age effect on nondisjunction.


The amphetamine challenge test correlates with affective lability in healthy volunteers.
The personality dimension of mood lability may be reflected in the mood response to the amphetamine challenge test. To test this hypothesis, the investigators acutely administered oral dextroamphetamine or placebo in a double-blind fashion to 11 normal control subjects who were free of any psychiatric disorders. Increased scores on interview and self-report measures of mood change during the challenge test, particularly increases in depression and anxiety, positively correlated with scores on the Affective Lability Scale, a measure of the lifetime personality trait of mood lability. These findings suggest that a dysphoric response to amphetamine is a marker for affective lability and that it may be useful to study this trait in patients with personality disorders.


Revisiting the evolutionary events in Allium subgenus Cyathophora (Amaryllidaceae): Insights into the effect of the Hengduan Mountains Region (HMR) uplift and Quaternary climatic fluctuations to the environmental changes in the Qinghai-Tibet Plateau.
The respective roles that the Hengduan Mountains Region (HMR) uplift around 4-3 Ma and Quaternary climatic oscillations played in causing the environmental changes in the Qinghai-Tibet Plateau (QTP) remain unknown. Here, we reconstruct the evolutionary history of two varieties of Allium cyathophorum and A. spicatum of subgenus Cyathophora, restricted to the HMR and the western QTP, respectively. Forty-five populations were surveyed for chloroplast and nuclear sequence variation to evaluate phylogenetic relationships, dates of divergence and ancestral area/inflorescence reconstructions. In addition, analyses were conducted on discernable micromorphologies, cytotypes and seed size variation. Our results indicated that two varieties of A. cyathophorum are separate species, i.e. A. farreri and A. cyathophorum, and the initial split of Cyathophora was triggered by the HMR uplift around 4-3 Ma. Subsequently, A. spicatum originated through the strengthened aridification in the western QTP induced vicariance of the ancestral populations in the HMR during the early Pleistocene. A self-sustaining allotetraploid species from A. farreri and A. cyathophorum was established during an interglacial period of penultimate glaciation of the QTP. Seed size variation also supports these by the colonization-competition tradeoff among small and large seeds. Our findings appear to suggest that the HMR uplift could have strengthened the development of the Asian monsoon regimes in this region and aridification in the western QTP, while the Quaternary climatic oscillations spurred the allopatric species' range shifts and created new open microhabitat for the alloploid species.


A test for intron function in the yeast actin gene.
Many eukaryotic genes contain intervening sequences (IVS), but the rationale for their existence remains a mystery. Previous studies done in our laboratory demonstrated that the intron in a yeast tRNATyr gene, SUP6, does have a function. We used the same approach to determine the role of introns in nuclear genes encoding messenger RNAs. A single actin gene with one intron exists in Saccharomyces cerevisiae. The level of actin in yeast appears to be crucial to viability: either too much or too little actin inhibits growth. Therefore, small effects on synthesis of actin protein resulting from the removal of the actin gene intron would be expected to cause measurable changes in cell growth. In the present study, an intron-deleted actin gene was constructed in vitro and was used to replace the single resident actin gene in a haploid strain. Analysis of the cells carrying the intron-deleted actin gene shows that the intervening sequence is not essential for actin gene expression.


Heat warning and public and workers' health at the time of COVID-19 pandemic.
The humanity is currently facing the COVID-19 pandemic challenge, the largest global health emergency after the Second World War. During summer months, many countries in the northern hemisphere will also have to counteract an imminent seasonal phenomenon, the management of extreme heat events. The novelty this year concerns that the world population will have to deal with a new situation that foresees the application of specific measures, including adjunctive personal protective equipment (i.e. facemasks and gloves), in order to reduce the potential transmission of the SARS-CoV-2 virus. These measures should help to decrease the risk of the infection transmission but will also represent an aggravating factor to counteract the heat effects on the population health both at occupational and environmental level. The use of a specific heat health warning system with personalized information based on individual, behavioural and environmental characteristics represents a necessary strategy to help a fast adaptation of the population at a time where the priority is to live avoiding SARS-CoV-2 infection.


Experiments on effects of an intermittent 16.7-Hz magnetic field on salivary melatonin concentrations, rectal temperature, and heart rate in humans.
The present experiments concerned the hypothesis that an intermittent, strong and extremely low frequency magnetic field reduces salivary melatonin levels and delays consecutively the nadirs of rectal temperature and heart rate. Twelve healthy young men (18-25 years) participated in three randomly permuted sessions, which were performed as constant routines. The participants kept a strict bed rest over 26 h, air temperature was 20 degrees C, illumination < 30 lx, and sound level < 50 dBA. Salivary melatonin levels were determined hourly, rectal temperature and heart rate were registered continuously throughout. An intermittent magnetic field was administered in one session from 6 p.m. to 2 a.m. at 16.7 Hz, 0.2 mT and alternating on/off-periods of 15 s. This situation was compared with a control session without any additional stress. Another session was performed to determine the participants' ability to respond to a well-known melatonin-suppressing stress, namely bright light (1,500 lx, 10 p.m.-2 a.m.). Bright light inhibited melatonin synthesis in all 12 participants and delayed the nadirs of rectal temperature and heart rate. The only significant alteration that was associated with exposure to the magnetic field was a delay in the heart rate nadir, which was not mediated by an accordingly altered melatonin profile. The fact that the circadian rhythm of only the heart rate was altered indicates an internal dissociation which might constitute a health risk in the long run and needs to be investigated more extensively.


The supplementary motor area exerts a tonic excitatory influence on corticospinal projections to phrenic motoneurons in awake humans.
In humans, cortical mechanisms can interfere with autonomic breathing. Respiratory-related activation of the supplementary motor area (SMA) has been documented during voluntary breathing and in response to inspiratory constraints. The SMA could therefore participate in the increased resting state of the respiratory motor system during wake (i.e. "wakefulness drive to breathe"). The SMA was conditioned by continuous theta burst magnetic stimulation (cTBS, inhibitory) and 5 Hz conventional rTMS (5 Hz, excitatory). The ensuing effects were described in terms of the diaphragm motor evoked response (DiMEPs) to single-pulse transcranial magnetic stimulation over the motor cortex. DiMEPs were recorded at baseline, and at 3 time-points ("post1", "post2", "post3") up to 15 minutes following conditioning of the SMA. cTBS reduced the amplitude of DiMEPs from 327.5 ± 159.8 µV at baseline to 243.3 ± 118.7 µV, 217.8 ± 102.9 µV and 240.6 ± 123.9 µV at post 1, post 2 and post 3, respectively (F = 6.341, p = 0.002). 5 Hz conditioning increased the amplitude of DiMEPs from 184.7 ± 96.5 µV at baseline to 270.7 ± 135.4 µV at post 3 (F = 4.844, p = 0.009). The corticospinal pathway to the diaphragm can be modulated in both directions by conditioning the SMA. This suggests that the baseline respiratory activity of the SMA represents an equipoise from which it is possible to move in either direction. The resting corticofugal outflow from the SMA to phrenic motoneurones that this study evidences could putatively contribute to the wakefulness drive to breathe.


Expression of c-mos protein in cultured rat spermatogenic cells and evidence that rat testicular 43 kDa c-mos protein has an elongated amino acid sequence at the N-terminus.
Expression of c-mos protein in rat spermatogenesis was examined by means of a cell culture system. A commercially available antibody (Cambridge Research Biochemicals, OA-11-861) was used to detect the protein. The 43 kDa c-mos (43K c-mos) protein was detectable in spermatogenic cells close to the occurrence of the first meiotic divisions (a few days before appearance of spermatids) during postnatal development, which was nearly consistent with expression in vivo. The results suggested that the c-mos protein has a role in meiotic maturation of spermatogenic cells. The 43K c-mos protein was partially purified from rat testes and the protein band was identified. The 43K c-mos protein had a pI value of around 9.0-9.6 having a hydrophobic nature, and was phosphorylated in vitro on serine. Neither ubiquitination nor glycosylation were detected. N-Terminal amino acid sequencing showed that the 43K c-mos protein has a Asp-Glu-Gly-Gly-Asn-Leu-Gln-sequence located 5' upstream (99 bases upstream) of the rat c-mos coding sequence reported. The amino acid analysis revealed a nearly consistent composition with that deduced from the DNA sequence. These results suggested that rat testicular 43K c-mos protein is translated from a 5' upstream sequence of the predicted consensus AUG start codon, probably by an unusual translational rule.


Indications for tube feedings in elderly patients.
Tube feedings are utilized in elderly patients with acute and chronic problems. Inadequate oral intake with malnutrition, comatose state, neurologic disorders with severe dysphagia, extensive burns, massive gastrointestinal resection, and oropharyngeal and upper gastrointestinal malignancies are the commonly encountered conditions requiring tube alimentation. Dysphagia with frequent aspiration is the most common indication for use of tube feedings in the elderly. Nasogastric tube is preferred for short-term feeding, while gastrostomy or jejunostomy is indicated for long-term or permanent nutritional support. Nutritional assessment should be done initially and on a regular basis. Specific formulas are available to calculate height, weight, and caloric needs of bedbound elderly patients. Various enteral feeding formulas are available for a specific clinical condition and are preferably administered by continuous drip using a pump. Parenteral nutrition is also indicated for certain situations in which enteral feeding cannot meet the patient's nutritional requirement, and in particular situations where enteral feeding is contraindicated and not feasible. Optimal patient care is dependent on adequate nutritional support.


J-Difference editing (MEGA) of lactate in the human brain at 3T.
The need to detect and quantify brain lactate accurately by MRS has stimulated the development of editing sequences based on J coupling effects. In J-difference editing of lactate, threonine can be co-edited and it contaminates lactate estimates due to the spectral proximity of the coupling partners of their methyl protons. We therefore implemented narrow-band editing 180° pulses (E180) in MEGA-PRESS acquisitions to resolve separately the 1.3-ppm resonances of lactate and threonine. Two 45.3-ms rectangular E180 pulses, which had negligible effects 0.15-ppm away from the carrier frequency, were implemented in a MEGA-PRESS sequence with TE 139 ms. Three acquisitions were designed to selectively edit lactate and threonine, in which the E180 pulses were tuned to 4.1 ppm, 4.25 ppm, and a frequency far off resonance. Editing performance was validated with numerical analyses and acquisitions from phantoms. The narrow-band E180 MEGA and another MEGA-PRESS sequence with broad-band E180 pulses were evaluated in six healthy subjects. The 45.3-ms E180 MEGA offered a difference-edited lactate signal with lower intensity and reduced contamination from threonine compared to the broad-band E180 MEGA. The 45.3 ms E180 pulse had MEGA editing effects over a frequency range larger than seen in the singlet-resonance inversion profile. Lactate and threonine in healthy brain were both estimated to be 0.4 ± 0.1 mM, with reference to N-acetylaspartate at 12 mM. Narrow-band E180 MEGA editing minimizes threonine contamination of lactate spectra and may improve the ability to detect modest changes in lactate levels.


Sunburn protection as a function of sunscreen application thickness differs between high and low SPFs.
Sunscreens are an important component of healthy sun-protection behavior. To achieve satisfactory protection, sunscreens must be applied consistently, evenly and correctly. Consumers do not apply sunscreen properly and, therefore, do not achieve the protection indicated by the label 'sun protection factor' (SPF). The objective of the present study was to determine the actual sun(burn) protection given by a range of sunscreen application thickness levels for both low and high SPF formulas. Forty study subjects were recruited from each of three geographical regions in China. Sunscreens with label SPFs of 4, 15, 30, and 55 were tested at application levels of 0.5, 1.0, 1.5, and 2.0 mg/cm(2) in three laboratories using a standard SPF protocol. Sunscreens with lower SPFs (4 and 15) showed a linear dose-response relationship with application level, but higher SPF (30 and 55) product protection was exponentially related to application thickness. Sunscreen protection is not related in one uniform way to the amount of product applied to human skin. Consumers may achieve an even lower than expected sunburn protection from high SPF products than from low SPF sunscreens.


Anti-Ro(SSA) positive rheumatoid arthritis (RA): a clinicoserological group of patients with high incidence of D-penicillamine side effects.
The clinical, laboratory, histological, and radiological manifestations of 90 Greek patients with anti-Ro(SSA) negative rheumatoid arthritis (RA) were compared with those of 15 Greek patients with anti-Ro(SSA) positive RA. Anti-Ro(SSA) positive RA patients had the same articular and extra-articular manifestations as anti-Ro(SSA) negative patients. However, they were predominantly females with lower rheumatoid factor titres and a high incidence of positive minor salivary gland biopsy specimens for Sjögren's syndrome. Finally, anti-Ro(SSA) positive RA patients frequently experienced penicillamine side effects.


Is minor salivary gland biopsy still mandatory in Sjogren's syndrome? Does seronegative Sjogren's syndrome exist?
Sjӧgren's disease (SjD) is a systemic autoimmune disorder characterized by the chronic inflammation and dysfunction of exocrine glands, mainly salivary glands, causing dryness of the eyes and of the mouth. The disease may affect different organs and tissues with complex and heterogeneous clinical presentation, usually with sicca symptoms, profound fatigue, chronic pain, major organ involvement, and lymphomas. SjD diagnosis is based on the combination of clinical, serological, and functional tests with histological biomarkers. Minor salivary gland biopsy (mSGB) represents the cornerstone for the diagnosis of SjD, allowing the study of the characteristic focal infiltration of B- and T lymphocytes. Besides, mSGB might also have a prognostic role, being the infiltrates more complex in patients with severe SjD. But biopsy, so far, is not mandatory for SjD and mSG ultrasound and peripheral biomarkers might replace its role in the future. Another important aspect of SjD is the presence of autoantibodies, although 20 to 30% of patients are "seronegative" for specific autoantibodies (ANA, antiRo/SSA, antiLa/SSB). The characteristics of this subset of patients are currently under evaluation and "new" autoantibodies and biomarkers might be necessary for better patient's stratification and follow-up.


Adsorptive stripping voltammetry of nickel with 1-nitroso-2-napthol using a bismuth film electrode.
A sensitive procedure is presented for the voltammetric determination of nickel. The procedure involves an adsorptive accumulation of nickel 1-nitroso-2-napthol (NN) complex on a bismuth film electrode prepared ex situ by electrodeposition. The most suitable operating conditions and parameters such as pH, ligand concentration (C(NN)), adsorptive potential (E(ads)), adsorptive time (t(ads)), scan rate and others were selected and the determination of nickel in aqueous solutions using the standard addition method was possible. The adsorbed Ni-NN complex gives a well defined cathodic stripping peak current at -0.70 V, which was used for the determination of nickel in the concentration range of 10.0-70.0 μg L(-1) (pH 7.5; C(NN) 6.5 μmol L(-1); E(ads) -0.30 V; t(ads) 60s) with a detection limit of 0.1 μg L(-1). The relative standard deviation for a solution containing 10.0 μg L(-1) of Ni(II) was 3.5% (n=4). The proposed method was validated determining Ni(II) in certified reference waste water (SPS-WW1) and Certified Reference Water for Trace Elements (TMDA 51.3) with satisfactory results. Then lake water samples were analyzed.


Identification of enigmatic Mediterranean fish Gobius ater Bellotti, 1888 (Teleostei: Gobiidae) based on morphology from underwater photographs.
Gobius ater Bellotti, 1888 is the Mediterranean gobiid species whose live appearance has remained unknown the longest since its description. A goby observed in southern France in 2021 is here identified as G. ater based on a diagnosis of morphological characters visible on high-quality underwater photographs. Then, the authors provide the first description of colouration in live G. ater and a species diagnosis based on colouration. This diagnosis allows the authors to validate a previous photographic record, also from France. Reviewing all claims of G. ater, they argue that only seven records are unambiguously valid, including the two photographic records presented here.


Neurotoxicity of paraquat and triphenyltin in the earthworm, Eisenia fetida Sav. A histo- and cytopathological study.
Neuropathological effects of the pesticides paraquat (PQ, a herbicide) and triphenyltin (TPT, a fungicide) were studied on the postclitellar segmental ganglia of juvenile E. fetida specimens using light and electron microscopic methods. Growth retardation of the worms in standard culture medium was used as quantitative marker of sublethal effect. There is a distinct neuron group in the segmental ganglia characterised by high sensitivity against PQ- and another one against TPT-toxication. However the marked histo- and neurocytopathological alterations were similar in PQ and TPT treated worms. Both chromatolysis and vacuolation of perikarya were revealed in sensitive neurons. Damaged cells were swollen and possessed degenerated rough endoplasmic reticulum cisternae. They were also characterised by swollen mitochondria, with electronlucent matrix and damaged inner membranes, and vesicular structures of various diameters as well as numerous lysosomes. Necrotic neurons with pyknotic nuclei and highly eosinophilic cytoplasm were also found in affected ganglia. Several dividing neurons were found in PQ-toxicated worms while no cell division occurred either in control or TPT-toxicated animals. The exact neurochemical and functional identification of PQ- and TPT-sensitive neurons needs further investigations.


Plasmonics for nanoimaging and nanospectroscopy.
The science of surface plasmon polaritons, known as "plasmonics," is reviewed from the viewpoint of applied spectroscopy. In this discussion, noble metals are regarded as reservoirs of photons exhibiting the functions of photon confinement and field enhancement at metallic nanostructures. The functions of surface plasmons are described in detail with an historical overview, and the applications of plasmonics to a variety of industry and sciences are shown. The slow light effect of surface plasmons is also discussed for nanoimaging capability of the near-field optical microscopy and tip-enhanced Raman microscopy. The future issues of plasmonics are also shown, including metamaterials and the extension to the ultraviolet and terahertz regions.


[Juvenile osteoporosis].
Osteoporosis is induced by a disorder of the bone turnover that generates an accelerated destruction process and leads to the rarefaction of the protein matrix. The RANK-L/RANK/OPG system is the main actor of the bone remodelling regulation. Juvenile osteoporoses may have primary or secondary aetiologies. The main causes include constitutional bone fragilities, and osteoporoses, which are secondary to chronic inflammatory diseases and sustained steroid treatment. Etiologic diagnosis relies on a clinical basis, and is often made too lately when complications occur. Osteodensitometry is a sensitive and noninvasive tool for measuring mineral bone density in children. The reliability of results is limited by the variations due to patients' age, gender, pubertal stage, and by the length of bone pieces. The optimal treatment of osteoporosis is preventive, and includes accurate nutritional diet, D vitamin-calcium supplementation and regular physical activity. Biphosphonates are used for treatment of symptomatic osteoporoses. Careful utilization is required in childhood because their late potential secondary effects are still unknown. New antiresorptive drugs and other that stimulate osteoformation are successfully used in adults. Their effects have not been studied in the paediatric population.


Post-translational Modifications of Nucleotide Excision Repair Proteins and Their Role in the DNA Repair.
Nucleotide excision repair (NER) is one of the major DNA repair pathways aimed at maintaining genome stability. Correction of DNA damage by the NER system is a multistage process that proceeds with the formation of multiple DNA-protein and protein-protein intermediate complexes and requires precise coordination and regulation. NER proteins undergo post-translational modifications, such as ubiquitination, sumoylation, phosphorylation, acetylation, and poly(ADP-ribosyl)ation. These modifications affect the interaction of NER factors with DNA and other proteins and thus regulate either their recruitment into the complexes or dissociation from these complexes at certain stages of DNA repair, as well as modulate the functional activity of NER proteins and control the process of DNA repair in general. Here, we review the data on the post-translational modifications of NER factors and their effects on DNA repair. Protein poly(ADP-ribosyl)ation catalyzed by poly(ADP-ribose) polymerase 1 and its impact on NER are discussed in detail, since such analysis has not been done before.


Correlation of histamine H1 receptor function and [3H]mepyramine binding in porcine tracheal tissue.
In order to validate the use of [3H]mepyramine as a radioligand to label airway histamine H1 receptors, the results of radioligand binding experiments using porcine tracheal tissue membranes were compared with the results of physiologic studies measuring histamine-induced trachealis muscle contraction. Close agreement was found between histamine-induced [3H]mepyramine binding inhibition and histamine concentration-contraction-response curves. Close agreement was also found between the KD of mepyramine-induced [3H]mepyramine binding inhibition and the K beta of mepyramine antagonism of muscle contractions stimulated by 10(-4) M histamine. [3H]Mepyramine binding was found to be rapid, reversible, saturable and stereospecific. Only H1 agonists and antagonists displayed potent [3H]mepyramine binding inhibition in competition binding studies. The results fulfill criteria for histamine H1 receptor identification by radioligand binding with [3H]mepyramine.


Treatment of Groundwater-Rich Organic Compounds Using Activated Carbon with Additional Germanium Dioxide (GeO2): Kinetics and Adsorption Studies of Methylene Blue and Congo Red.
Activated carbon/GeO2 composites were synthesized using the sol-gel method and then used as catalysts for the photodegradation of organic pollutants methylene blue (MB) and congo red (CR). The composites were characterized using an X-ray diffractometer and Fourier transform infrared spectroscopy to analyze the structure and chemical bonds of the composite materials, respectively. The ultraviolet-visible (UV-vis) absorption wavelength ranges of the composites toward the pollutants were 550-700 nm for MB and 450-550 for CR. The band gap energies of the composites were calculated, with the values found to be <4.5 eV. It was shown that the adsorption ability of the composites increased with the irradiation time of the pollutants. Furthermore, the adsorption kinetics data were found to be a good fit to a pseudo-first-order kinetics model.


[No influence of imatinib on type 2 diabetes].
Five patients with type 2 diabetes, three of them treated with insulin and two with oral antidiabetic drugs, receiving imatinib due to chronic myeolid leukaemia are reported. Treatment with imatinib 400 mg/day for 7 to 37 (mean 24.2) months had no positive effect on clinical course of type 2 diabetes.


Tunneled island pedicle flap reconstruction for upper lateral cutaneous lip defects.
Esthetic upper lateral cutaneous lip reconstruction preserves the apical triangle, nasolabial fold symmetry, and free margin position. The tunneled island pedicle flap (IPF) is a novel single-stage reconstruction to achieve these goals. Describe the technique and patient and surgeon-reported outcomes for the tunneled IPF reconstruction of upper lateral cutaneous lip defects. Retrospective chart review of consecutive tunneled IPF reconstruction following Mohs micrographic surgery (MMS) at a tertiary care center between 2014 and 2020. Patients rated their scars using the validated Patient Scar Assessment Scale (PSAS), and independent surgeons rated scars using the validated Observer Scar Assessment Scale (OSAS). Descriptive statistics were generated for patient demographics and tumor defect characteristics. Twenty upper lateral cutaneous lip defects were repaired with the tunneled IPF. Surgeons rated scars with a composite OSAS score of 11.83 ± 4.29 (mean, SD) [scale of 5 (normal skin) to 50 (worst scar imaginable)] and an overall scar score of 2.81 ± 1.11 [scale of 1 (normal skin) to 10 (worst scar imaginable)]. Patients rated their scars with a composite PSAS score of 10 ± 5.39 [scale of 6 (best possible score) to 60 (worst)] and with an overall score of 2.2 ± 1.78 [scale of 1 (normal skin) and 10 (very different from normal skin)]. One flap was surgically revised for pincushioning, but none experienced necrosis, hematoma, or infection. The tunneled IPF is a single-stage reconstruction for upper lateral cutaneous lip defects with favorable scar ratings by patients and observers.


Paired helical filaments in neurovisceral lipidosis (juvenile dystonic lipidosis).
Paired helical filaments, the ultrastructural substrate of Alzheimer neurofibrillary change, were found in great number in a 29-year-old patient with neurovisceral lipidosis. The abnormal filaments were frequently present in the distended neurons and axons. The clinical, pathological, and ultrastructural findings were consistent with juvenile dystonic lipidosis, which is considered to be a variant of type C Niemann-Pick disease. The association of Alzheimer neurofibrillary change and central nervous system lipidosis is reviewed.


Functional recruitment of newborn hippocampal neurons after experimental stroke.
The adult brain responds to diverse pathologies such as stroke with increased generation of neurons in the dentate gyrus of the hippocampus. However, only little is known regarding the functional integration of newborn neurons into pre-existing neuronal circuits. In this study, we investigated whether newborn neurons generated after experimental stroke are recruited for different behavioral tasks. Adult mice received photochemical cortical infarcts in the sensorimotor cortex and proliferating cells were labeled using the proliferation marker, bromodeoxyuridine. Eight weeks after stroke induction, the animals were trained to perform either a spatiotemporal task or a sensorimotor task. Immediate early gene expression (c-fos, Zif268) in newborn neurons was analyzed directly after the last session. Using this approach, we demonstrate that post-stroke generated neurons are recruited within the hippocampal networks. The sensorimotor task activates significantly more newborn neurons compared to the spatiotemporal task. Further experiments employing the two well-established stimulators of neurogenesis, enriched environment and voluntary wheel running, both significantly increase post-stroke neurogenesis in the dentate gyrus but do not affect the percentage of recruited neurons compared to controls. Significantly, the spatiotemporal task leads to a higher portion of activated newborn neurons in the granule cell layer, suggesting a specific spatial activation pattern of new neurons in the dentate gyrus.


Separation of Light Gases from Xenon over Porous Organic Cage Membranes.
Herein, we demonstrate the successful synthesis and separation ability of CC3 porous organic cage membranes grown on tubular supports for light gases He, CO2, CH4, and Kr over xenon. CC3 membranes were synthesized using secondary seeded growth and displayed different separation performances depending on the crystal size, size distribution of the seeds, and membrane thickness. CC3 membranes as thin as ∼2.5 μm resulted in high single gas permeances of 2114, 1962, 1705, 773, and 162 GPU, for He, CH4, CO2, Kr, and Xe, respectively. The highest ideal selectivities for He/Xe, CH4/Xe, CO2/Xe, and Kr/Xe gas pairs were 13, 12, 10.5, and 4.8, respectively. Mechanistically, the membranes separated He, CO2, Kr, and CH4 from Xe mainly via gas diffusivity differences. Therefore, the separation was kinetically driven.


The impact of public-private investment in energy on environmental degradation: evidence from major investment countries.
The objective of the present study is to explore the impact of public-private investment in energy, foreign direct investment, urbanization, and renewable and non-renewable energy consumption on environmental degradation in major investment countries during the period 1998Q4-2018Q4. In doing so, the cross-sectional dependence test and CIPS panel unit test were employed to identify the cross-sectionally dependency and the integrational properties/stationarity among the variables. Furthermore, we opted for Westerlund (2007) panel cointegration test to check the long-run association among the variables. To achieve the short-run and long-run elasticities, we have recommended cross-sectional-autoregressive distributive lag (CS-ARDL). The study outcomes revealed that public-private partnership in energy is negatively and significantly impacting CO2 emissions in both the short run and the long run. Furthermore, foreign direct investment and urbanization are negatively related to CO2 emissions, while renewable energy is positively affected it. However, the coefficients are insignificant. Moreover, non-renewable energy has a positive and substantial influence on CO2 emissions. Lastly, study outcomes offer several policy insights to develop investment in public and private partnerships in the energy sector to reduce CO2 emissions in major investment countries.


[Resection of caudate lobe of liver: report of 26 cases].
To summarize the experience in caudate lobectomy for 26 cases. Caudate lobectomy was performed in 26 cases by Peng's multifunctional operative dissector (PMOD) to transect the liver parenchyma (Curettage and Aspiration technique). Primary liver cancer was noted in 18 cases, hilar cholangiocarcinoma in 4, gallbladder carcinoma in 1, right adrenocortical adenocarcinoma in 1, hepatoangioma in 1 and hepatoangiosarcoma in 1. Five cases underwent isolated caudate lobectomy, 1 combined caudate lobectomy with right trisegmentectomy, 6 combined caudate lobectomy with right hemihepatectomy, 9 combined caudate lobectomy with left hemihepatectomy, and 5 combined caudate lobectomy with segmentectomy. The operations were carried out successfully. Follow up for 2 - 23 months, 1 case died from pulmonary infraction 2 weeks after operation, 1 died from lung metastasis 2 months after operation, 10 died from tumor recurrence or metastasis 3, 11, 12, 15, 15, 15, 15, 19, 30, 30 months after operation respectively. The other 14 cases are still alive for 2 to 18 months. With PMOD, it is possible to dissect the structure precisely. Therefore the caudate lobe can be isolated from the three porta hepatis without much difficulty. Caudectomy can be performed safely.


MOF derived ZnO/C nanocomposite with enhanced adsorption capacity and photocatalytic performance under sunlight.
In this work, ZnO/C nanocomposites were obtained by calcining the prepared metal-organic framework precursor under nitrogen. The crystallinity and structure of the prepared products were characterized by XRD, FTIR, XPS and EDS. The morphologies of samples before and after calcination were observed by FESEM. The photocatalytic performances of ZnO/C were evaluated by the degradation of methylene blue under sunlight irradiation. Combined with DRS, PL and BET, the influence of calcination temperature on photocatalytic activities of as-synthesized zinc oxide were discussed as compared with commercial zinc oxide. The results indicated that ZnO/C composite obtained at 600 °C and 700 °C exhibited the superior adsorption capacity and photocatalytic activity. The possible photocatalytic mechanism of ZnO/C nanocomposite for degradation of MB under sunlight irradiation was proposed.


Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Mild Cognitive Impairment and Alzheimer's Disease: A Meta-Analysis.
Background: Alzheimer's disease (AD) is a progressive and multifactorial neurodegenerative disease accounting for 80% of dementia worldwide. Objective: To assess the influence of probiotics on cognitive function in patients with mild cognitive impairment (MCI) and AD. Methods: PubMed, Embase, and Cochrane Library databases were searched for relevant studies. Results: Six randomized controlled trials involving 462 patients with MCI and AD were included in this meta-analysis. The probiotic administration had favorable effects on homeostasis model assessment-insulin resistance [HOMA-IR; Weighted mean difference (WMD) = -0.34, 95% confidence intervals (95% CI): -0.44 to 0.24, P < 0.001, I 2 = 0%], very low-density lipoprotein levels (VLDL; WMD = -3.71, 95% CI: -6.11 to -1.32, P=0.002, I 2 = 57.7%), quantitative insulin sensitivity check index (QUICKI; WMD = 0.01, 95% CI: 0.00-0.01, P = 0.003, I 2 = 51%), and triglyceride levels (WMD = -15.65, 95% CI: -27.48 to -3.83, P = 0.009, I 2 = 63.4%) in patients with AD. However, after Hartung-Knapp adjustment, all effects were non-significant except for HOMA-IR (MD = -0.34, 95%CI = -0.58 to -0.11). The changes in the Mini-Mental State Examination, repeatable battery for the assessment of neuropsychological status, and other biomarkers of oxidative stress, inflammation, and lipid profiles (high-sensitivity C-reactive protein, malondialdehyde, and total cholesterol) were negligible. Conclusion: The findings suggested that the consumption of probiotics had favorable effects on the HOMA-IR in patients with AD. However, the probiotic treatment did not affect cognitive function, other biomarkers of oxidative stress, and other lipid profiles.


Viscosity of deeply supercooled water and its coupling to molecular diffusion.
The viscosity of a liquid measures its resistance to flow, with consequences for hydraulic machinery, locomotion of microorganisms, and flow of blood in vessels and sap in trees. Viscosity increases dramatically upon cooling, until dynamical arrest when a glassy state is reached. Water is a notoriously poor glassformer, and the supercooled liquid crystallizes easily, making the measurement of its viscosity a challenging task. Here we report viscosity of water supercooled close to the limit of homogeneous crystallization. Our values contradict earlier data. A single power law reproduces the 50-fold variation of viscosity up to the boiling point. Our results allow us to test the Stokes-Einstein and Stokes-Einstein-Debye relations that link viscosity, a macroscopic property, to the molecular translational and rotational diffusion, respectively. In molecular glassformers or liquid metals, the violation of the Stokes-Einstein relation signals the onset of spatially heterogeneous dynamics and collective motions. Although the viscosity of water strongly decouples from translational motion, a scaling with rotational motion remains, similar to canonical glassformers.


The "Brazilian" bikini-shaped lip-reduction technique: new developments in cheiloplasty.
The lips, one of the most illustrious facial features, have a key role in forming facial expressions. In the past, hypertrophic lips were an aesthetic issue among certain ethnic groups. Although full lips are a desirable feature sought by many people, the current world of fashion tends emphasize equilibrium and significant matching of features, encouraging people to seek refinement through cosmetic surgery. The purpose is to reach the standard level of perceived attractiveness in current society. This article aims to present a novel lip reduction technique that restores an attractive labial contour by shifting the shape toward a more "Brazilian way" and resulting in more aesthetically appealing lips. The technique described in this report was performed on more than 40 patients between 2008 and 2010. The major difference between this technique and others is that it transforms the shape of the bikini lines to a more "Brazilian" way. The upper resection is more conservative, whereas the lower resection is less triangular and more curved, displaying more of the bilateral "bands" on the lips. The reported patients did not present any infections or any other complications. The nature of human beings urges them to seek routes of assimilation into their society. This also applies to the rules of perceived attractiveness. The technique presented in this article has recaptured specific attention to the resultant lip contour, altering the shape of the marks on the lower lip. The new technique yields a harmonious relationship between the upper and lower lips. The aesthetic results and patient satisfaction attained through this novel technique of lip reduction have been very satisfactory. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.