Challenges facing the More Doctors program (Programa Mais Médicos) in vulnerable and peri-urban areas in Greater Brasilia, Brazil.
A shortage of physicians, especially in vulnerable and peri-urban areas, is a global phenomenon that has serious implications for health systems, demanding policies to assure the provision and retention of health workers. The aim of this study was to analyze the strategies employed by the More Doctors Program (Programa Mais Médicos) to provide primary care physicians in vulnerable and peri-urban parts of Greater Brasilia. The study used a qualitative approach based on the precepts of social constructivism. Forty-nine semi-structured interviews were conducted: 24 with physicians employed as part of the More Doctors program, five with program medical supervisors, seven with secondary care physicians, twelve with primary care coordinators, and one federal administrator. The interviews occurred between March and September 2019. The transcripts of the interviews were submitted to thematic content analysis. The partnership between the Ministry of Health and local authorities was essential for the provision of doctors-especially foreign doctors, most from Cuba, to assist vulnerable population groups previously without access to the health system. There was a notable presence of doctors with experience working with socioeconomically disadvantaged populations, which was important for gaining a better understanding of the effects of the endemic urban violence in the region. The incentives and other institutional support, such as enhanced salaries, training, and housing, transportation, and food allowances, were factors that helped provide a satisfactory working environment. However, the poor state of the infrastructure at some of the primary care units and limitations of the health service as a whole were factors that hampered the provision of comprehensive care, constituting a cause of dissatisfaction. More Doctors introduced a range of novel strategies that helped ensure a supply of primary care doctors in vulnerable and peri-urban parts of Greater Brasilia. The inclusion of foreign doctors, most from Cuba, was crucial for the success of the health services provided for the local communities, who subsist in violent and socioeconomically deprived urban areas. However, it became clear that barriers from within the health service itself hampered the physicians' capacity to provide a satisfactory service. As such, what is needed for primary care to be effective is not just the recruitment, training, and deployment of doctors, but also investment in the organization of the whole health system.


The inheritance of glomerulosclerosis in mice is controlled by multiple quantitative trait loci.
Glomerulosclerosis, the common terminal event in chronic glomerular diseases such as diabetic nephropathy or IgA nephropathy, leads to end-stage renal disease. The considerable variation in both the risk of developing glomerulosclerosis and the rate of progression in individual patients suggest a role for genetic factors which have not been identified so far. In this study we sought to examine the mode of inheritance of glomerulosclerosis in mice. F1 animals of a mating between glomerulosclerosis-prone ROP-Os/+ male and non-sclerotic C3H female mice were backcrossed to the ROP strain. We took advantage of the radiation-induced mutation oligosyndactylism (Os) to identify glomerulosclerosis at the age of 3 months. Kidneys were perfused in situ with PBS/Formalin 10%. The extent of glomerulosclerotic lesions was evaluated on PAS stained paraffin sections using computer-aided morphometry. F1 mice did not show any glomerulosclerosis. In the backcross offspring, we found a wide distribution of glomerular lesions between individual animals, ranging from normal to very severe. We calculated that at least 8-10 loci determine the severity of glomerulosclerosis in mice. Our data show that glomerulosclerosis is inherited in a recessive fashion involving at least 8-10 loci.


Trapping Reactions of Benzynes Initiated by Intramolecular Nucleophilic Addition of a Carbonyl Oxygen to the Electrophilic Aryne.
We describe here reactions in which a carbonyl oxygen atom initiates cascade reactions by nucleophilic attack on a covalently attached benzyne. The benzynes are produced by thermal cyclization of triynes via hexadehydro-Diels-Alder reaction. The initially produced oxocarbenium/aryl carbanionic zwitterion is protonated in situ by an external protic nucleophile (NuH) of appropriate acidity. The resulting ion pair (oxocarbenium+/Nu-) collapses through several different mechanistic manifolds, adding to the diversity of structural classes that can be generated.


Red Blood Cell Transfusion, Anemia, Feeding, and the Risk of Necrotizing Enterocolitis.
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants. Severe anemia and red blood cell (RBC) transfusion are associated with gut inflammation and injury in preclinical models and observational studies. However, there is uncertainty about the causal role of these factors in the pathogenesis of NEC. Observational studies have shown that withholding feeding during RBC transfusion may reduce the risk of NEC, although confirmatory data from randomized trials are lacking. In this review, we summarize data on feeding during RBC transfusion and its role in NEC and highlight ongoing randomized trials.


A patient lifting intervention for preventing the work-related injuries of nurses.
The average age of nurses is projected to be 50 years in 2010 [17]. Because nurses are older, a work injury prevention program should change how nurses lift patients. The purpose of this evidence-based practice improvement project was to examine a new lifting intervention. An evidence-based process was used to implement an effective lifting intervention, including a back school, a lift team, and mechanical lifting equipment, on the orthopedic and neurology units in a Minnesota hospital. A two-week pilot determined if enough work would be generated to justify hiring a permanent lift team. Then the entire lifting intervention was studied on the two units. The injuries for the two units decreased from 21 to 9 injuries, while the salary and work replacement costs were $48,220 and $2,560 in 2001 and 2002, respectively. The lift team averaged 80 lifts per day and 95% of the nursing staff attended the back school. The lift team and new mechanical lifting equipment were successfully disseminated resulting in significant reductions in costs. Suggested improvements include additional supervision and lift team scheduling changes, regular staff meetings, and ongoing education.


Characterization of the cellular and metabolic effects of a novel enzyme-resistant antagonist of glucose-dependent insulinotropic polypeptide.
A novel N-terminally substituted Pro(3) analogue of glucose-dependent insulinotropic polypeptide (GIP) was synthesized and tested for plasma stability and biological activity both in vitro and in vivo. Native GIP was rapidly degraded by human plasma with only 39 +/- 6% remaining intact after 8 h, whereas (Pro(3))GIP was completely stable even after 24 h. In CHL cells expressing the human GIP receptor, (Pro(3))GIP antagonized the cyclic adenosine monophosphate (cAMP) stimulatory ability of 10(-7) M native GIP, with an IC(50) value of 2.6 microM. In the clonal pancreatic beta cell line BRIN-BD11, (Pro(3))GIP over the concentration range 10(-13) to 10(-8) M dose dependently inhibited GIP-stimulated (10(-7) M) insulin release (1.2- to 1.7-fold; P < 0.05 to P < 0.001). In obese diabetic (ob/ob) mice, intraperitoneal administration of (Pro(3))GIP (25 nmol/kg body wt) countered the ability of native GIP to stimulate plasma insulin (2.4-fold decrease; P < 0.001) and lower the glycemic excursion (1.5-fold decrease; P < 0.001) induced by a glucose load (18 mmol/kg body wt). Collectively these data demonstrate that (Pro(3))GIP is a novel and potent enzyme-resistant GIP receptor antagonist capable of blocking the ability of native GIP to increase cAMP, stimulate insulin secretion, and improve glucose homeostasis in a commonly employed animal model of type 2 diabetes.


The effects of wind and temperature on cuticular transpiration of Picea abies and Pinus cembra and their significance in dessication damage at the alpine treeline.
The importance of high winter winds and plant temperatures as causes of winter desiccation damage at the alpine treeline were studied in the Austrian Alps. Samples of 1- and 2-year twigs of Picea abies and Pinus cembra were collected from the valley bottom (1,000 m a.s.l.), forestline (1,940 m a.s.l.), kampfzone (2.090 m a.s.l.), wind-protected treeline (2,140 m a.s.l.), and wind-exposed treeline (2,140 m a.s.l.). Cuticular transpiration was measured at three different levels of wind speed (4, 10, and 15 ms-1) and temperature (15°, 20°, and 25° C). At elevated wind speeds slight increases in water loss were observed, whereas at higher temperatures much greater increases occurred. Studies on winter water relations show a significant decline in the actual moisture content and osmotic potentials of twigs, especially in the kampfzone and at treeline. The roles of high winds and temperatures in depleting the winter water economy and causing desiccation damage in the alpine treeline environment are discussed.


First-stage palliation for hypoplastic left heart syndrome in the twenty-first century.
Improved understanding of the postoperative physiology and experience with the surgical techniques and perioperative care of patients with hypoplastic left heart syndrome have resulted in improved outcomes. Over the past few years, numerous modifications to the intraoperative and postoperative management of these patients have been described. It is likely that in combination, these modifications and better understanding of the unique physiology after the Norwood procedure are responsible for decreasing early mortality. This review describes and discusses the current surgical and medical management of patients undergoing first-stage palliation for hypoplastic left heart syndrome and its variants.


PR depression is useful in the differential diagnosis of myopericarditis and ST elevation myocardial infarction.
Deviation of the PR segment is a common but often ignored ECG finding in acute myopericarditis, but seems to be rare in the acute phase of ST elevation myocardial infarction (STEMI). Since rapid bedside differential diagnosis of acute myopericarditis and STEMI is essential, we decided to assess the diagnostic power of PR depressions in patients presenting with ST elevations in the emergency room. Thirty-four consecutive patients with acute myopericarditis and 46 STEMI patients presenting with ST elevations fulfilling the criteria for STEMI were included. The first ECG recorded in the emergency room was analyzed with a focus on the PR segment. The diagnoses of myopericarditis and STEMI were ascertained with clinical follow-up together with rise in troponin levels, and in the STEMI patients also with coronary angiography. In myopericarditis, the most common location for PR depression was lead II (55.9%), while this ECG finding least likely appeared in lead aVL (2.9%). PR depression in any lead had a high sensitivity (88.2%), but fairly low specificity (78.3%) for myopericarditis. The combination of PR depressions in both precordial and limb leads had the most favorable predictive power to differentiate myopericarditis from STEMI (positive 96.7% and negative power 90%). Our present observations show that PR segment analysis is a powerful tool in the differential diagnosis of myopericarditis and STEMI. This simple information should be added to the diagnostic workup of patients presenting with ST elevations.


Formation and persistence of DNA adducts in the liver of brown bullheads exposed to benzo[a]pyrene.
The formation and persistence of benzo[a]pyrene (BP)-DNA adducts in the liver of brown bullheads (Ictalurus nebulosus) treated with the hydrocarbon (20 mg/kg body wt, i.p.) was investigated using the 32P-postlabeling assay. The highest level of covalent binding of BP to liver DNA (188 fmol BP adducts/mg DNA) was observed 25-30 days following treatment. After 70 days, the adduct level in liver DNA had declined to approximately 26% of the maximum adduct level. One major BP-DNA adduct and several minor ones were detected in the liver. The major adduct co-chromatographed with anti-BP-7,8-diol-9,10-epoxide-deoxyguanosine (anti-BPDE-dGuo) adduct. The data suggest that brown bullheads metabolically activate BP by the same mechanism as the mammalian systems susceptible to carcinogenic effects of the hydrocarbon.


Effectiveness of Neuromuscular Electrical Stimulation on Patients With Dysphagia With Medullary Infarction.
To evaluate and compare the effects of neuromuscular electrical stimulation (NMES) acting on the sensory input or motor muscle in treating patients with dysphagia with medullary infarction. Prospective randomized controlled study. Department of physical medicine and rehabilitation. Patients with dysphagia with medullary infarction (N=82). Participants were randomized over 3 intervention groups: traditional swallowing therapy, sensory approach combined with traditional swallowing therapy, and motor approach combined with traditional swallowing therapy. Electrical stimulation sessions were for 20 minutes, twice a day, for 5d/wk, over a 4-week period. Swallowing function was evaluated by the water swallow test and Standardized Swallowing Assessment, oral intake was evaluated by the Functional Oral Intake Scale, quality of life was evaluated by the Swallowing-Related Quality of Life (SWAL-QOL) Scale, and cognition was evaluated by the Mini-Mental State Examination (MMSE). There were no statistically significant differences between the groups in age, sex, duration, MMSE score, or severity of the swallowing disorder (P>.05). All groups showed improved swallowing function (P≤.01); the sensory approach combined with traditional swallowing therapy group showed significantly greater improvement than the other 2 groups, and the motor approach combined with traditional swallowing therapy group showed greater improvement than the traditional swallowing therapy group (P<.05). SWAL-QOL Scale scores increased more significantly in the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups than in the traditional swallowing therapy group, and the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups showed statistically significant differences (P=.04). NMES that targets either sensory input or motor muscle coupled with traditional therapy is conducive to recovery from dysphagia and improves quality of life for patients with dysphagia with medullary infarction. A sensory approach appears to be better than a motor approach.


A multi-residue method for trace analysis of pesticides in soils with special emphasis on rigorous quality control.
A multi-residue trace analytical method is presented to accurately quantify 146 currently used pesticides in (agricultural) soils with varying soil properties. Pesticides were extracted using an optimized quick, easy, cheap, effective, rugged, and safe (QuEChERS) approach and chemical analysis was carried out by liquid chromatography coupled to tandem mass spectrometry (triple quadrupole). Quantification was based on matrix-matched internal standards calibration, using 95 isotopically labeled analyte analogues. In contrast to the common approach of method validation using soils freshly spiked with analytes shortly before the extraction, our method is additionally validated via an in-house prepared partly aged soil, which contains all target pesticides and via agricultural field soils with native pesticide residues. The developed method is highly sensitive (median method limit of quantification: 0.2 ng/g), precise (e.g., median intra-day and inter-day method precision both ~ 4% based on field soils), and true ((i) quantified pesticide concentrations of the partly aged soil remained stable during 6 months, were close to the initially spiked nominal concentration of 10 ng/g, and thus can be used to review trueness in the future; (ii) median freshly spiked relative recovery: 103%; and (iii) participation in a ring trial: median z-scores close to one (good to satisfactory result)). Its application to selected Swiss (agricultural) soils revealed the presence of in total 77 different pesticides with sum concentrations up to 500 ng/g. The method is now in use for routine soil monitoring as part of the Swiss Action Plan for Risk Reduction and Sustainable Use of Plant Protection Products.


Duck hepatitis B virus (DHBV) as a model for understanding hepadnavirus neutralization.
The role of the immune response to the human hepatitis B virus (HBV) envelope proteins in neutralization of viral infectivity has been well documented. The similarity between HBV, prototype member of the hepadnavirus family, and the closely related duck hepatitis B virus (DHBV) has allowed, use of the latter as a convenient model for the study of molecular mechanisms of HBV replication and neutralization. In this brief review, we will examine the HBV and DHBV envelope proteins and their role as targets for virus neutralization.


Cyclic AMP analog activates Na(+)-dependent inward currents in dissociated frog motoneurons.
Effects of intracellular accumulation of 3',5'-cyclic adenosine monophosphate (cAMP) were studied using 3',5'-cyclic 8-bromoadenosine monophosphate (8-Br-cAMP) and forskolin on single motoneurons acutely dissociated from adult bullfrog spinal cord. 8-Br-cAMP (10(-3) M) and forskolin (1.5 x 10(-6) M) activated inward currents under K(+)-free conditions at a holding potential of -70 mV. The currents were dependent on extracellular Na+ concentration, and were never reversed within the range of membrane potentials tested (-130 to 30 mV). These results indicate that accumulation of intracellular cAMP induces Na(+)-dependent inward currents in frog motoneurons.


Organizational design: the case of SARS-CoV-2 vaccination in a healthcare centre.
Only recently Anti-Covid-19 strategies have been applied through specific vaccines, that are a decisive support to modify the evolution of the disease and to reduce the contagion curve. Along vaccination campaigns, the necessity to guarantee rapidity and effectiveness is a critical challenge for all health organizations; their operative capability is applied to carry out govern plans, to ensure safety of the procedures, to adopt good clinical practices, to help with adhesion to vaccine administration and to monitor adverse effects. The "Centro Clinico Morgagni" is a private accredited diagnosis and treatment Centre with high specialty departments and several hospital beds. The challenge for its administration was to complete the vaccination of all the staff, so a COVID19 crisis unit was established to assure the control of all activities in the center throughout the pandemic. The goal was to complete the vaccination plan following the guidelines with no risks or harm. An original organizational model, based on different planning methodologies was developed, its task was to define a standard procedure and to give operational instructions based on ISO 9001 for monitoring the entire vaccination process. Also, the model had to define every responsibility role and it had to follow Joint Commission International's methodologies as far as error barriers, drug conservation risks, drug transport and drug administration were concerned.Furthermore, in agreement with the HACCP system, critical control points were highlighted during all the process. The results have been processed in the form of quick references and illustrative panels based on relevant process aspects, which were given to the staff involved in the operations as reference tools for prompt consultation. The vaccination operations at the Centro Clinico Morgagni took place quickly in only four days: 800 staff units were vaccinated - first and second doses with Covid19 mRNA BNT162b2 (Cominraty) - in three different vaccination centers without highlighting significant events that did not comply with the guidelines, nor deviations from the established goals. More precisely, starting from 277 bottles corresponding to six doses each, only 0.2% was wasted, while ADR monitoring reported a prevalence of adverse effects in females (78%) compared to males (22%). Adhesion for vaccination of qualified personnel, thanks to the activities of the Medical College set up for this purpose, reached 100% of the candidate staff through repeated personalized interviews with only one opposition, compared to the 30 communicated at the beginning. It was necessary to ensure the efficiency of the entire process and the model was tested positively. This model can also provide a security control of all the vaccinated personnel; its schematization allows an easy application and flexibility, thus making it an organizational tool that could be reproduced and transferred to other contexts.


Urogenital and Rectal Multisystem Organ Injury After Detonation of an Explosive Substance in the Rectum of a Schizophrenic Man.
Penetrating injuries are caused by the injury of perineal area with gun or stab wounds, which may cause complex injuries or multiple organ injuries. Infections, bleeding, necrotizing fasciitis, ureterocutaneous fistulas, diverticulum, abscesses, narrowing, and incontinence may arise after urethral injuries. Although there are several case reports of urogenital system traumas in the literature, this case reports a schizophrenic patient who had a multisystem genitourinary and rectal trauma after self-detonation of an explosive in the rectum and managed with reconstructive surgery without any postoperative complications. Lower urinary tract anatomy was preserved and full continence was achieved after the surgical procedure.


What future for superconductivity ?
Progress in the theory of superconductors, particularly consideration of macrowave functions, could provide many opportunities for future development.


Enhancer reprogramming in mammalian genomes.
Transcription factor binding site (TFBS) loss, gain, and reshuffling within the sequence of a regulatory element could alter the function of that regulatory element. Some of the changes will be detrimental to the fitness of the species and will result in gradual removal from a population, while other changes would be either beneficial or just a part of genetic drift and end up being fixed in a population. This "reprogramming" of regulatory elements results in modification of the gene regulatory landscape during evolution. We identified reprogrammed enhancers (RPEs) by comparing the distribution of tissue-specific enhancers in the human and mouse genomes. We observed that around 30% of mammalian enhancers have been reprogrammed after the human-mouse speciation. In 79% of cases, the reprogramming of an enhancer resulted in a quantifiably different expression of a flanking gene. In the case of the Thy-1 cell surface antigen gene, for example, enhancer reprogramming is associated with cortex to thymus change in gene expression. To understand the mechanisms of enhancer reprogramming, we profiled the evolutionary changes in the TFBS enhancer content and found that enhancer reprogramming took place through the acquisition of new TFBSs in 72% of reprogramming events. Our results suggest that enhancer reprogramming takes place within well-established regulatory loci with RPEs contributing additively to fine-tuning of the gene regulatory program in mammals. We also found evidence for acquisition of novel gene function through enhancer reprogramming, which allows expansion of gene regulatory landscapes into new regulatory domains.


Genotoxicity of organic chemicals frequently found in the air of mobile homes.
The 19 chemicals most commonly detected in a study of mobile homes in Texas were tested for mutagenicity using a battery of bacterial test strains; the literature was searched to obtain additional information concerning the mutagenicity and carcinogenicity of these chemicals. Formaldehyde was found to be present in 100% of the mobile homes and at the highest mean concentration (167 ppb). The remaining organic chemicals were all present at much lower mean concentrations (less than 10 ppb) and at varying frequencies (2-95%). Of the 19 chemicals tested for mutagenicity, only formaldehyde gave a positive response. A review of the literature revealed that 4 of the chemicals tested, formaldehyde, styrene, tetrachloroethylene and benzene, have been shown to be animal and/or human carcinogens. Thus, formaldehyde is not the only genotoxin present in the air of mobile homes but because it was present in the air of all mobile homes tested at much higher concentrations than the other organic chemicals, formaldehyde should be considered one of the major potential genotoxic hazards present in the air of mobile homes.


In vitro metabolism of deoxycoformycin in human T lymphoblastoid cells. Phosphorylation of deoxycoformycin and incorporation into cellular DNA.
The biochemical and metabolic effects of deoxycoformycin, a potent inhibitor of adenosine deaminase, were investigated using two human T lymphoblastoid cell lines. A dose-response analysis demonstrated that the concentration of deoxycoformycin at which there was 50% inhibition of growth was greater than 1 X 10(-3) M in lymphoblastoid cells. Uptake of deoxycoformycin was biphasic and occurred much more slowly than for natural nucleosides, and lower saturation levels were reached. The intracellular concentration of deoxycoformycin achieved was 0.4 to 0.5 microM when the extracellular concentration was 1 microM. At 10 microM extracellular concentration, the intracellular concentration was 3-4 microM. Although deoxycoformycin at very low concentrations (1 or 10 microM) did not have any detectable effects on the growth of these cells, the nucleoside was found to be metabolized, and was phosphorylated to give the mono-, di-, and triphosphate derivatives. The triphosphate derivative was incorporated into cellular DNA with little incorporation into cellular RNA. Metabolism of deoxycoformycin in several mutant lymphoblastoid cells deficient in adenosine kinase and/or deoxycytidine kinase was found to be unchanged from wild-type cells, indicating that these major nucleoside kinases do not play a significant role in the phosphorylation of deoxycoformycin. These results may account, at least in part, for the differences that are observed between the pharmacologic inhibition of adenosine deaminase, and the inherited deficiency of adenosine deaminase.


Robustified maximum likelihood estimation in generalized partial linear mixed model for longitudinal data.
In this article, we study the robust estimation of both mean and variance components in generalized partial linear mixed models based on the construction of robustified likelihood function. Under some regularity conditions, the asymptotic properties of the proposed robust estimators are shown. Some simulations are carried out to investigate the performance of the proposed robust estimators. Just as expected, the proposed robust estimators perform better than those resulting from robust estimating equations involving conditional expectation like Sinha (2004, Journal of the American Statistical Association99, 451-460) and Qin and Zhu (2007, Journal of Multivariate Analysis98, 1658-1683). In the end, the proposed robust method is illustrated by the analysis of a real data set.


Pilomatrixoma mimicking breast carcinoma.
A case of pilomatrixoma occurring in the breast of a middle-aged male is presented. Many of the clinical features of this case were not typical of a pilomatrixoma and it was originally diagnosed clinically as a breast carcinoma.


SPME-based mobile field device for active sampling of volatiles.
Monitoring plant volatile organic compound (VOC) profiles can reveal information regarding the health state of the plant, such as whether it is nutrient stressed or diseased. Typically, plant VOC sampling uses sampling enclosures. Enclosures require time and equipment which are not easily adapted to high throughput sampling in field environments. We have developed a new, easily assembled active sampling device using solid phase microextraction (SPME) that uses a commercial off the shelf (COTS) hand vacuum base to provide rapid and easy mobile plant VOC collection. Calibration curves for three representative plant VOCs (α-pinene, limonene, and ocimene) were developed to verify device functionality and enable the quantification of field-samples from a Meyer lemon tree. We saw that the active sampling allowed us to measure and quantify this chemical in an orchard setting. This device has the potential to be used for VOC sampling as a preliminary diagnostic in precision agriculture applications due to its ease of manufacturing, availability, and low cost of the COTS hand vacuum module.


COVID-PA Bulletin: reports on artificial intelligence-based forecasting in coping with COVID-19 pandemic in the state of Pará, Brazil.
To report the university extension research result entitled 'The COVID-PA Bulletin', which presented forecasts on the behavior of the pandemic in the state of Pará, Brazil. The artificial intelligence technique also known as 'artificial neural networks' was used to generate 13 bulletins with short-term forecasts based on historical data from the State Department of Public Health information system. After eight months of predictions, the technique generated reliable results, with an average accuracy of 97% (observed for147 days) for confirmed cases, 96% (observed for 161 days) for deaths and 86% (observed for 72 days) for Intensive Care Unit bed occupancy. These bulletins have become a useful decision-making tool for public managers, assisting in the reallocation of hospital resources and optimization of COVID-19 control strategies in various regions of the state of Pará.


Dynamical phenomena: walking and orbiting droplets.
Small drops can bounce indefinitely on a bath of the same liquid if the container is oscillated vertically at a sufficiently high acceleration. Here we show that bouncing droplets can be made to 'walk' at constant horizontal velocity on the liquid surface by increasing this acceleration. This transition yields a new type of localized state with particle-wave duality: surface capillary waves emanate from a bouncing drop, which self-propels by interaction with its own wave and becomes a walker. When two walkers come close, they interact through their waves and this 'collision' may cause the two walkers to orbit around each other.


Estimation of the elimination half-life of a drug at any serum concentration when the Km and Vmax of the drug are known: calculations and validation with phenytoin.
A method of estimating the elimination half-life of a drug at any selected serum concentration when the Km and Vmax of that drug are known is described. The method was validated in six patients by determining their Km and Vmax values for phenytoin, using data obtained at two serum concentrations and then using the Km and Vmax values to predict the elimination half-life of phenytoin at a third serum concentration. The predicted elimination half-lives at the third serum concentration did not differ significantly (t = 1.16, P = .30) from observed elimination half-lives determined with stable isotope tracer techniques.


Ciliated hepatic foregut cyst: report of first case in China and review of literature.
To report the first case of ciliated hepatic foregut cyst in China, and review of literature to introduce the characteristics of this disease for doctors to recognize this disease. Report the clinical procedure of diagnosis and treatment for the first case of ciliated hepatic foregut cyst in China, and to review the embryologic genesis, incidence, clinical manifestation, radiologic features and therapeutic principle of this disease. We performed the resection for ciliated hepatic foregut cyst under laparoscopy; the patient recovered well after the procedure. Ciliated hepatic foregut cyst is quite rare clinically, belongs to non-parasitic, solitary and unilocular cystic lesion, is always less than 4 cm in diameter, mostly seen in the left lobe, and has the tendency of malignant change. It should be removed as soon as diagnosed.


Health-related quality of life in patients with chronic respiratory failure after long-term mechanical ventilation.
This study was aimed at assessing health-related quality of life (HRQL) in patients with chronic respiratory failure (CRF) and long-term survival following prolonged intensive care mechanical ventilation. Observational cohort study. Patients with CRF who had been transferred to our specialized weaning centre due to prolonged mechanical ventilation (>14 days) and weaning failure. Out of 87 long-term survivors (>6 months), 73 patients (mean age: 60.3+/-13.6 years, chronic obstructive pulmonary disease (COPD, 43%), thoraco-restrictive (21%) or neuromuscular disorders (15%), various chronic diseases (22%)) returned the MOS 36-Item Short-Form Health Status Survey (SF-36) and the St. George's respiratory questionnaire (SGRQ). The total ventilation time was 38.7+/-45.9 days. The time between discharge from ICU and HRQL assessment was 31.0+/-22.2 months. Physical health was markedly reduced compared to general population norm, but mental health was mildly impaired. HRQL was comparable to patients with stable CRF receiving non-invasive ventilation who did not need prolonged invasive MV. In addition, general HRQL was better in patients with restrictive respiratory disease compared to patients with neuromuscular diseases (P<0.05). Physiological parameters such as blood gases or lung function parameters were not correlated to any HRQL measurements. In patients with CRF surviving prolonged ventilation on ICU, the presence of CRF itself is the major determinant of HRQL. Here, the underlying cause of CRF is the major factor which determines the degree of HRQL impairment with patients suffering from restrictive ventilatory disorders reporting the best HRQL when compared to patients with COPD or neuromuscular diseases. Despite severe physical handicaps due to CRF mental health is only mildly compromised.


A One-Bag Rapid Desensitization Protocol for Paclitaxel Hypersensitivity: A Noninferior Alternative to a Multi-Bag Rapid Desensitization Protocol.
Desensitization is used to safely continue treatment with a culprit drug in patients with drug hypersensitivity. Currently, a multi-bag protocol is widely used for rapid desensitization, but performing the desensitization procedure is labor intensive as pharmacists and nurses need to prepare and administer diluted solutions. However, it has not been investigated whether dilution is essential for successful desensitization. To investigate the efficacy and safety of a nondilution, 1-bag protocol in comparison with a conventional multi-bag protocol for desensitization of patients with paclitaxel hypersensitivity. Patients who underwent paclitaxel desensitization between 2011 and 2018 were analyzed in this retrospective cohort study. The completion rate, time to completion, and occurrence and severity of breakthrough reaction (BTR) between a 1-bag protocol and a multi-bag protocol were compared. A total of 211 desensitization procedures were performed, of which 207 procedures (98.1%) were completed successfully. The administration time was significantly shorter in the 1-bag protocol group compared with the conventional multi-bag protocol group (266.0 ± 149.3 minutes vs 484.2 ± 178.6 minutes, P < .05) without differences in the completion rate (97.6% vs 98.9%, P = .645), the incidence of BTR (16.1% vs 27.6%, P = .778), and the proportion of severe BTR (2.6% vs 5.7%, P = .134). A nondilution, 1-bag protocol is noninferior to a multi-bag rapid desensitization protocol and can be a safe and effective option for paclitaxel desensitization.


Impact of Comprehensive Health Insurance on Quality of Life in Low-Income Hispanic Men with Prostate Cancer.
To evaluate the effect of the transition from IMPACT, a disease-focused treatment program, to comprehensive health insurance under Medicaid through the Affordable Care Act (ACA) on general and prostate cancer-specific quality of life (QoL) on a cohort of previously uninsured low-income men. We hypothesize that general QoL would improve and prostate cancer-specific QoL would remain the same after the transition to comprehensive health insurance. We assessed and compared general QoL using the RAND SF-12v2™ (12-Item Short Form Survey, version 2) and prostate cancer-specific QoL using the UCLA PCI (Prostate Cancer Index) one year before, at, and one year after the transition between 30 men who transitioned to comprehensive insurance (newly insured/Medicaid group) and 54 men who remained in the prostate cancer program (uninsured/IMPACT group). We assessed the independent effects of Medicaid coverage on QoL outcomes using repeated-measures regression. Our cohort was composed primarily of Hispanic men (82%). At transition, patient demographics and clinical characteristics were similar between the groups. General and prostate cancer-specific QoL did not differ between the groups and remained stable over time, Radical prostatectomy as primary treatment and shorter time since treatment were associated with worse urinary and sexual function across both groups and over all three time points. Those who transitioned to full-scope insurance and those who remained in the free prostate cancer-focused treatment program had stable general and prostate cancer-specific QoL. High-touch navigation aspects of a disease-focused program may have contributed to stability in outcomes.


Draft genome sequence of Pseudomonas fuscovaginae, a broad-host-range pathogen of plants.
Pseudomonas fuscovaginae was first reported as a pathogen of rice causing sheath rot in plants grown at high altitudes. P. fuscovaginae is now considered a broad-host-range plant pathogen causing disease in several economically important plants. We report what is, to our knowledge, the first draft genome sequence of a P. fuscovaginae strain.


Glycobiology of the oral pathogen Porphyromonas gingivalis and related species.
Until recently, glycoproteins had only been described in eukaryotes. However, advances in detection methods and genome analyses have allowed the discovery of N-linked or O-linked glycoproteins, similar to those found in eukaryotes, in some bacterial species. These prokaryotic glycoproteins play roles in adhesion, solubility, formation of protein complexes, protection from protein degradation, and changes in antigenicity. Periodontal pathogen Porphyromonas gingivalis secretes virulence proteins via the type IX secretion system, some of which localize on the cell surface by binding to lipopolysaccharide (LPS). These virulence proteins have a conserved C-terminal domain (CTD) region, which is used as a secretion signal. However, it is still uncertain how the secreted proteins on the cell surface bind to LPS. In this review, we discuss the synthesis of P. gingivalis O polysaccharide, which plays a role in anchoring the CTD protein on the cell surface, and recent discoveries of glycoproteins in P. gingivalis as well as other species in the phylum Bacteroidetes.


Complete genome of Staphylococcus aureus Tager 104 provides evidence of its relation to modern systemic hospital-acquired strains.
Staphylococcus aureus (S. aureus) infections range in severity due to expression of certain virulence factors encoded on mobile genetic elements (MGE). As such, characterization of these MGE, as well as single nucleotide polymorphisms, is of high clinical and microbiological importance. To understand the evolution of these dangerous pathogens, it is paramount to define reference strains that may predate MGE acquisition. One such candidate is S. aureus Tager 104, a previously uncharacterized strain isolated from a patient with impetigo in 1947. We show here that S. aureus Tager 104 can survive in the bloodstream and infect naïve organs. We also demonstrate a procedure to construct and validate the assembly of S. aureus genomes, using Tager 104 as a proof-of-concept. In so doing, we bridged confounding gap regions that limited our initial attempts to close this 2.82 Mb genome, through integration of data from Illumina Nextera paired-end, PacBio RS, and Lucigen NxSeq mate-pair libraries. Furthermore, we provide independent confirmation of our segmental arrangement of the Tager 104 genome by the sole use of Lucigen NxSeq libraries filled by paired-end MiSeq reads and alignment with SPAdes software. Genomic analysis of Tager 104 revealed limited MGE, and a νSaβ island configuration that is reminiscent of other hospital acquired S. aureus genomes. Tager 104 represents an early-branching ancestor of certain hospital-acquired strains. Combined with its earlier isolation date and limited content of MGE, Tager 104 can serve as a viable reference for future comparative genome studies.


Treatment of lip florid papillomatosis with topical ALA-PDT combined with curettage: Outcome and safety.
Photodynamic therapy (PDT) is a successful treatment in clinical practice. PDT is increasingly used to cure the patients with skin cancer, especially in the elder. The purpose of this study was to evaluate the treatment outcome and safety of PDT with aminolevulinic acid (5-ALA) combined with surgical curettage for lip florid papillomatosis. In this study, 4 cases of lip florid papillomatosis were treated with topical aminolevulinic acid photodynamic therapy (ALA-PDT) combined with curettage. First, the warts were removed with the patient under local anesthesia. The depth of the ablation and curettage reached the dermal layer. Then, the first session of PDT was performed after 2days. Ten percent 5-ALA cream was applied to lesional skin with occlusive dressing for a 3-h incubation period and the lesions of warts were irradiated for 10min by using a 635-nm laser beam of 177mW/cm2 intensity. The ALA-PDT was repeated after 1 and 3 weeks and two other treatments applied if necessary. Follow-up evaluation was performed at our outpatient clinic at 3 and 6 months after completion of therapy. After three PDT sessions following surgical curettage, 3 patients were cured at 3 months off treatment, one cases relapsed, corresponding to a recurrent rate of 25%. There was no other recurrence at 6 months off treatment. The satisfaction rate of patients was 95% at 3 month and 100% at 6 months after treatment. The combined treatment of topical ALA-PDT and curettage was proven to be safe and effective in lip florid papillomatosis.


Gender-specific association of the PTPN22 C1858T polymorphism with achalasia.
The protein tyrosine phosphatase N22 (PTPN22) gene encodes a lymphoid-specific phosphatase (LYP), a downregulator of T-cell activation. Because a functional PTPN22 polymorphism, C1858T, has been found to be associated with different autoimmune diseases, we aimed to elucidate the role of this variant in predisposition to achalasia. We performed a case-control study with 231 nonrelated Spanish patients of white ethnicity diagnosed with achalasia and in 554 healthy control subjects, all genotyped for PTPN22 C1858T using TaqMan chemistry. The frequency of the 1858T allele was higher in the achalasia patients than in the healthy controls (carriers of allele T vs CC: OR = 1.38, 95% confidence interval [95% CI] 0.88-2.16, p = 0.13). Moreover a different genotype distribution was found between female and male patients (carriers of allele T vs CC: OR = 2.06, 95% CI 0.96-4.42, p = 0.04) and also between female patients and controls (OR = 1.94, 95% CI 1.12-3.36, p = 0.01), but not between male patients and controls (OR = 0.94, 95% CI 0.50-1.77, p = 0.85). We conclude that the PTPN22 1858T allele is a susceptibility factor for Spanish women with achalasia.


Patterns and Correlates of Self-Reported Physical Activity in a Cohort of Racially Diverse Pregnant Adolescents.
Regular physical activity (PA) during pregnancy decreases the risk of gestational hypertension and preeclampsia. Currently, little is known about the PA of pregnant adolescents. Our intent was to characterize the PA behaviors of a group of racially diverse, low-income pregnant teens and to identify potential determinants of PA. A cohort of 157 racially diverse pregnant adolescents (13-18 years of age) completed up to 3 previous day PA recalls as part of a larger prospective longitudinal study on determinants of maternal and fetal bone health. Subjects self-reported activities from 7 AM to 11:30 PM, choosing from a list of 37 activities including a category for "other." Subjects recorded activities in 30-minute intervals. Estimated metabolic equivalent task (MET) values were assigned to each activity and summed for a measure of total daily PA in MET min/d. Determinants of PA were evaluated using a stepwise linear mixed effect model. The average calculated MET min/d was 1478 ± 130. Significant determinants of MET min/d included race (P = .007), maternal age at conception (P = .042), gestational age (P = .002), and attending school (P < .001). Black teens were less physically active than white teens, and older teens were more active than younger teens; activity decreased throughout gestation, and teens currently attending school were more active. PA is low across gestation and pregnant teens spent more than half of their monitored time in sedentary activities. Targeted interventions are needed to achieve current PA goals in this pediatric obstetric population.


Sex, stress, and fear: individual differences in conditioned learning.
It has long been recognized that humans vary in their conditionability, yet the factors that contribute to individual variation in emotional learning remain to be delineated. The goal of the present study was to investigate the relationship among sex, stress hormones, and fear conditioning in humans. Forty-five healthy adults (22 females) underwent differential delay conditioning, using fear-relevant conditioned stimuli and a shock unconditioned stimulus. Salivary cortisol samples were taken at baseline and after acquisition training and a 24-h-delayed retention test. The results showed that acquisition of conditioning significantly correlated with postacquisition cortisol levels in males, but not in females. This sex-specific relationship was found despite similar overall levels of conditioning, unconditioned responding, and cortisol. There was no effect of postacquisition cortisol on consolidation of fear learning in either sex. These findings have implications for the understanding of individual differences in fear acquisition and risk factors for the development of affective disorders.


Alcohol and liver cancer.
Hepatocellular carcinoma is the eighth most frequent cancer in the world, accounting for approximately 500,000 deaths per year. Unlike many malignancies, hepatocellular carcinoma occurs predominantly within the context of known risk factors, with hepatic cirrhosis being the most common precursor to the development of hepatocellular carcinoma. After ethanol ingestion, the liver represents the major site of metabolism. Ethanol metabolism by alcohol dehydrogenase leads to the generation of acetaldehyde and free radicals that bind rapidly to numerous cellular targets, including components of cell signaling pathways and DNA. In addition to direct DNA damage, acetaldehyde depletes glutathione, an antioxidant involved in detoxification. Chronic ethanol abuse leads to induction of hepatocyte microsomal cytochrome P450 2E1, an enzyme that metabolizes ethanol to acetaldehyde and, in doing so, causes further free radical production and aberrant cell function. Cytochrome P450 2E1-dependent ethanol metabolism is also associated with activation of procarcinogens, changes in cell cycle, nutritional deficiencies, and altered immune system responses. The identification of oxidative stress in mediating many deleterious effects of ethanol in the liver has led to renewed interest in the use of dietary antioxidants as therapeutic agents. Included in this group are S-adenosyl-L-methionine and plant-derived flavanoids.


[Hemithyroidectomy: when it is necessary an intraoperative frozen-section biopsy?].
Many surgeons use intraoperative frozen section biopsy of the thyroid nodules to confirm malignant disease, but it continues to generate considerable controversy. We reviewed our recent experience to determinate de clinical utility of frozen section in our surgical management and intraoperative decision-making. All patients who had operations for the thyroid nodular disease between 2000 and 2006 were included in this retrospective study. We compared the results of frozen section diagnosis and definitive histologic results in a population of 212 patients. Frozen section was false negative in 3 patients (1.66 %) and false positive in 1 (0.47 %) and avoided 12 reoperations (5.6 %). When there was not suspicious malignant disease had a sensitivity of 0.75 %. In the group of follicular disease the sensitivity was 3.7 %, and in the group with suspicious malignant disease was 37.5 %. Frozen section was more helpful in the group of suspicious for malignant disease. It does not seem to be necessary when fine-needle biopsy indicates bening or follicular disease.


Quality of life and psychological impact in adult patients with hemorrhagic moyamoya disease who received no surgical revascularization.
Surgical treatment for adult hemorrhagic moyamoya disease (MMD) remains controversial. A large proportion of Chinese adult patients with hemorrhagic MMD still choose conservative treatment. In this study, we investigated to assess psychological function and quality of life (QoL) in adult patients with hemorrhagic MMD who received no surgical revascularization. 26 adult patients with hemorrhagic MMD who presented with only intraventricular hemorrhage (IVH), 20 patients with spontaneous IVH whose DSA results were negative and 30 healthy controls were identified and matched for age, gender, living area, etc. Psychological function and QoL were evaluated by Short Form-36 (SF-36), Symptom Check List 90 (SCL-90), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS) and daily life questionnaire respectively one year after the initial stroke. Multiple logistic regression model was built up to screen out the independent risk factors related to depression and reduced QoL. Heavier social and mental burden was observed in adult patients with hemorrhagic MMD compared with the patients with spontaneous IVH. The QoL of cases was particularly reduced in the psychological domains. 19 (73%) cases developed depression, indicating the probable higher incidence of psychological disorder in Asian patients. Multiple logistic regression analysis suggested the independent risks of reduced QoL and depression involved in personality types and education background. Our data revealed that poor education background or introverted personality type may be attributed to the development of depression in Chinese adult hemorrhagic MMD patients who received no surgical revascularization associated with QoL impairment. The treatment decisions for these patients should consider the possible improvement of QoL.


Biphasic effect of local anesthetic and beta-blocker heptacaine on fluidity of phosphatidylcholine bilayers as detected by ESR spin probe method.
Heptacaine (1), the monohydrochloride of [2-(heptyl-oxy)phenyl]-2-(1-piperidinyl)ethyl ester of carbamic acid, exerts a biphasic effect on the fluidity of egg yolk phosphatidylcholine (EYPC) model membranes as detected by the methyl esters of stearic acid spin probes with the paramagnetic doxyl group bound to the C-12 or C-16. The fluidity initially increases with an increase in the molar ratio of 1:EYPC, but a molar ratios above 1:EYPC = 0.5 a decrease of fluidity has been observed.


Pharmacokinetics of famotidine in normal subjects and in patients with chronic liver disease.
The pharmacokinetics of famotidine were studied in seven healthy control subjects and in 14 patients with cirrhosis, following single oral and intravenous 20-mg dose administration, and after seven daily doses of 40 mg. Following intravenous (i.v.) administration, the mean (range) total plasma clearance values were not significantly different in the patients with compensated cirrhosis (n = 7), 337 (241-576) ml/min or in the patients with decompensated cirrhosis (n = 7), 270 (120-408) ml/min compared with the control group, 370 (154-612) ml/min. The mean half-life in the compensated cirrhotics, 2.86 (1.87-4.98) h, was similar to that in the control group 2.91 (1.86-6.03) h, but it was insignificantly prolonged in the decompensated cirrhotics 3.35 (2.00-5.77) h. The mean, maximum, plasma famotidine concentrations after single oral doses were comparable between the groups but there was considerable inter-subject variability, with individual values ranging from 17 to 139 ng/ml. Peak plasma concentrations were reached within 2-3 h, although more variability was observed among patients with decompensated cirrhosis. The mean systemic availability of the drug, estimated from urinary recovery, was 0.39 (0.15-0.64) in the healthy controls, 0.35 (0.14-0.51) in the patients with compensated cirrhosis and 0.38 (0.13-0.77) in the patients with decompensated cirrhosis. No significant increases were observed in plasma trough famotidine concentrations following multiple oral dosing in any of the subjects, and the kinetic variables after the seventh dose were not significantly different from those following the single oral dose. No significant changes were observed in psychometric performance in control subjects or in patients between the pre-study day and day seven of the multiple oral dose phase.


Synthesis, antimicrobial and anticancer activities of a novel series of diphenyl 1-(pyridin-3-yl)ethylphosphonates.
A novel series of diphenyl 1-(arylamino)-1-(pyridin-3-yl)ethylphosphonates 1-5 was obtained in high yields from reactions of 3-acetyl pyridine with aromatic amines and triphenylphosphite in the presence of lithium perchlorate as a catalyst. The structures of the synthesized compounds were confirmed by IR, (1)H NMR spectral data and microanalyses. Compounds 1-5 showed high antimicrobial activities against Escherichia coli (NCIM2065) as a Gram-negative bacterium, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as Gram-positive bacteria and Candidaalbicans and Saccharomyces cerevisiae as fungi, at low concentrations (10-100 μg/mL). Also, the synthesized compounds showed significant cytotoxicity anticancer activities against liver carcinoma cell line (HepG2) and human breast adenocarcinoma cell line (MCF7). The lethal dose of the synthesized compounds was also determined and indicated that most compounds are safe to use.


Bronchial mucous gland tumours.
Tumours arising in the bronchial mucous glands closely resemble tumours arising in the mixed salivary glands. Bronchial mucous gland tumours account for less than 0.5 per cent of all lung tumours. Twenty six tumours are reviewed and they have been divided into five types, (a) adenoidcystic carcinomas, (b) muco-epidermoid tumors, (c) mixed (pleomorphic) tumors, (d) cystadenomas and (f) oxyphilic adenoma. The clinical features, and postoperative course of the patients are reviewed. Adenocystic carcinomas, arising in the bronchus frequently involve the neighbouring trachea and spread mainly by direct infiltration. Most muco-epidermoid bronchial tumours were confined to young persons, and the only malignant muco-epidermoid tumour occurred in an elderly person. The prognosis in young persons is good provided the tumours are completely excised. The two mixed bronchial tumours resembled their salivary counterparts and one subsequently behaved as a carcinoma and metastasised. Bronchial cystadenomas all proved to be benign tumours but in two cases were associated with surface papillary proliferation. The only example of an oxyphil cell adenoma was discovered at post mortem examination. The histogenesis of the tumours is considered.


Electrophysiological evidence for preparatory reconfiguration before voluntary task switches but not cued task switches.
An unresolved issue in the task-switching literature is whether preparatory reconfiguration occurs before a change of task. In this study, we used event-related potentials (ERPs) to determine whether preparatory reconfiguration occurs during two different task-switching procedures: voluntary and cued task switching. We focused on two ERP components that index different cognitive operations. The contingent negative variation (CNV) is a sensitive measure of a participant's preparedness to use a specific stimulus-response mapping. In contrast, the P3 indexes memory updating. We found a pronounced modulation of the CNV before voluntary task switches, but not before cued task switches. Instead, cued task switches were preceded by a larger P3, as compared with task repetitions. Our findings suggest that task set reconfiguration is carried out prior to voluntary task switches, whereas memory processes dominate cued task switches.


The efficacy, tolerability and safety of a new oral formulation of Sandimmun--Sandimmun Neoral in severe refractory atopic dermatitis.
To investigate the efficacy, tolerability and safety of a new oral formulation of Sandimmun-Sandimmun Neoral in severe refractory atopic dermatitis in an open, multicenter study. The study was conducted in three parts. After 2 weeks of screening, Sandimmun Neoral was commenced at a dose of 3 mg/kg per day and continued until remission or for a maximum of 8 weeks, after which the dose was reduced by half and continued for another 2 weeks and then discontinued. After the treatment period, patients were followed up first for 8 weeks and then until relapse or for a maximum of 24 weeks. Twenty-three patients with severe refractory atopic dermatitis (15 females, eight males) mean age 27.2 +/- 14.6 years (range 13-70 years) entered and 22 patients completed the study (one drop-out due to withdrawal of consent). After the end of the full-dose (mean duration 6.5 weeks) and half dose treatment periods, the SCORAD index decreased by 82 and 90%, respectively. Improvement started as early as at 2 and 4 weeks of treatment (mean reduction in SCORAD: 37.5 and 71.7%). At the end of the treatment phase, reductions in EDS, intensity of disease, DSS, pruritus, and sleep loss were 85, 88, 79, 85 and 96%, respectively. The overall efficacy was assessed as very good or good in 96 and 100% of the patients at the end of treatment and after 8 weeks follow-up, respectively. During the follow-up of 24 weeks after treatment, 73% of the patients had a relapse, whereas 27% were still in remission at the end of 24 weeks. In the 22 patients who completed the study, no adverse events were noted which would have necessitated dose reduction or drug withdrawal. Tolerability was assessed as very good or good in 91 and 96% of the patients, at the end of treatment and after 8 weeks follow-up, respectively. Adverse events observed were: nausea (18%), hirsutism (9%), headache (4.5%), epigastric pain (4.5%), paresthesia (4.5%), furuncle (4.5%), and herpes labialis (4.5%). No significant changes in vital signs, hematological and biochemical parameters and serum creatinine were observed during the study except eosinophilia which was reduced by 40% towards the end of treatment. Our results suggested that short-term (8 weeks), low dose (3 mg/kg per day) Sandimmun Neoral treatment is an effective, safe, and well-tolerated treatment for atopic dermatitis refractory to conventional treatment modalities and can lead to long-term remission of the disease in some patients. However, a double-blind, placebo controlled, long-term follow-up study would be necessary to confirm these results.


MR-guided percutaneous core biopsy of small breast lesions: first experience with a vertically open 0.5T scanner.
The growing use of highly sensitive but only moderate specific breast MRI requires the development of both minimal-invasive as well as precise biopsy systems. The aim of the study was to prove the accuracy and feasibility of a biopsy procedure carried out in prone position in a vertically opened MR imager. The biopsies were carried out in 21 women with lesions visible on MRI alone using an open breast coil with an integrated biopsy device. A 14 G coaxial needle was placed under near real-time MRI-guidance. After the tip of this needle was verified in contact with the lesion, we used a non MR-compatible, but MR-safe biopsy gun with a 16 G canula to take four to eight cores. We found eight malignant and 12 benign lesions. In one patient the procedure was not successful. In case of malignancy, the operation confirmed the diagnosis in all cases. The 12/21 patients with benign lesions have been followed without evidence of lesions growth over eight to 28 months. The described procedure allows MRI-guided minimal invasive core biopsy of small breast lesions (five to 17 mm) with a high degree of accuracy.


Pelvic ureteral angiomyoma mimicking urothelial carcinoma: A case report.
Angiomyoma is a rare benign tumor that can occur in any organ with smooth muscles. No one has already described an angiomyoma of the ureter. We report the case of a 44 year old woman who presented with intermittent hematuria and left flank pain. The diagnosis of left ureteral tumor was evoked by the scannographic aspect. She underwent a radical nephro-ureterectomy. Final histological examination concluded to ureteral angiomyoma. Angiomyoma is rare benign smooth muscle tumor with a vascular component. Symptomatology depends on the organ that angiomyoma is developed from, and is usually mimicking malignant tumors. Symptomatology, radiologic findings are mimicking urothelial carcinomas, however the pathology corrected the diagnostic error.


Number of Sexual Partners and Relationship Status Are Associated With Unprotected Sex Across Emerging Adulthood.
Sex with multiple partners, consecutively or concurrently, is a risk factor for contracting sexually transmitted infections (STIs) as multiple partner-partner contacts present increased opportunity for transmission. It is unclear, however, if individuals who tend to have more partners also use protection less reliably than those with sexual histories of fewer partners. Longitudinal data can elucidate whether an individual shows a consistent pattern of sex with multiple partners. We used latent class growth analyses to examine emerging adult survey data (N = 2244) spanning 10 waves of assessment across 6 years. We identified three trajectory classes described with respect to number of partners as (a) Multiple, (b) Single, and (c) Rare. Trajectory group, relationship status, and their interactions were tested as predictors of using protection against STIs and pregnancy at each wave. The Multiple Partners class had the greatest odds ratio of reporting sex without protection against STIs and pregnancy, followed by the Single and Rare classes. Exclusive relationship status was a risk factor for unprotected sex at earlier waves, but a protective factor at most later waves. There was no significant interaction between relationship status and trajectory class in predicting use of protection. The Multiple Partners class reported more permissive values on sex and an elevated proportion of homosexual behavior. This group overlaps with an already identified at-risk population, men who have sex with men. Potential mechanisms explaining the increased risk for sex without protection, including communication, risk assessment, and co-occurring risk behaviors are discussed as targets for intervention.


Retinoic acid signaling affects cortical synchrony during sleep.
Delta oscillations, characteristic of the electroencephalogram (EEG) of slow wave sleep, estimate sleep depth and need and are thought to be closely linked to the recovery function of sleep. The cellular mechanisms underlying the generation of delta waves at the cortical and thalamic levels are well documented, but the molecular regulatory mechanisms remain elusive. Here we demonstrate in the mouse that the gene encoding the retinoic acid receptor beta determines the contribution of delta oscillations to the sleep EEG. Thus, retinoic acid signaling, which is involved in the patterning of the brain and dopaminergic pathways, regulates cortical synchrony in the adult.


One-stage hypospadias repair.
A surgical technique for correction of hypospadias with chordee in one stage is described. This technique which brings the ectopic meatus up to the tip of the glans was successfully applied in 3 cases of penoscrotal and in 8 cases of penile hypospadias.


STROBE-A preliminary investigation of IVIM-DWI in cardiac imaging.
This study aims to explore the possibility to apply intravoxel incoherent motion-magnetic resonance imaging (IVIM-MRI) in cardiac imaging.Multi-b-value diffusion-weighted imaging (DWI) sequence scanning was performed on 12 healthy volunteers. A double exponential model was adopted, and the b-value sequence was 0, 20, 60, 80, 120, 200, and 600 second/mm. The D-value, D*-value, and f-value of the anterior posterior and lateral walls of the ventricular septum were respectively measured on the short axis section of the heart, the parameters of the myocardium in different blood supply areas in each segment were recorded, and the measured data of these different segments were compared using analysis of variance.Among these 12 healthy volunteers, the D-value, D*-value, and f-value of these 72 segments were not exactly equal, the D-values of the myocardium in the 5th and 11th segment were lower than those in the 2nd, 3rd, 8th, and 9th segments, and the pairwise differences were statistically significant (P < .001). Furthermore, the difference in D-value between the 5th and 11th segments was not statistically significant (P = 1.000). The D*-value and f-value of the myocardium in the 5th and 11th segment were higher than those in the 2nd, 3rd, 8th, and 9th segments, and the pairwise differences were statistically significant (P < .001). Furthermore, the differences in D*-value and f-value between the 5th and 11th segments was not statistically significant (P = .214, .787).The intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) technique can quantitatively reflect the diffusion and blood perfusion status of the myocardium.


Topological organization of NADPH-oxidase in haematopoietic stem cell membrane: preliminary study by fluorescence near-field optical microscopy.
The aim of this study was to characterize the local distribution and organization of the plasma membrane NADPH-oxidase (NOX) in human haematopoietic stem cell (HSC) by means of the fluorescence scanning near-field optical microscopy approach. The presence of NOX in haematopoietic stem cells is thought to have a functional role as O(2) sensor and/or as low-level reactive oxygen species (ROS) producer to be used as redox messenger for controlling cell growth and differentiation. Given the harmful potential of ROS, a fine-tuning of NOX activity is needed. The high resolution imaging of haematopoietic stem cell membrane obtained in this study combined with the immunodetection of NOX indicates for this the occurrence of a cluster-organized structure. These membrane 'rafts'-like micro-compartments may constitute localized protein aggregates whereby the assembly/activation of the NOX components are functionally integrated with upstream factors constituting signal-transduction platforms.


Inhibitory effect of prolactin on Toxoplasma proliferation in peripheral blood mononuclear cells from patients with hyperprolactinemia.
Despite many years of studies on the mechanisms of immunological defence responses induced in host organisms by Toxoplasma, no satisfactory immunoprophylaxis or chemotherapy have yet been established for humans. Thus, alternative methods to prevent toxoplasmosis and to enhance the efficacy of currently used antitoxoplasmic drugs are under evaluation. In this work, we strove to determine the influence of human prolactin (endogenous present in serum--sPRL and recombinant--rhPRL) on the course of Toxoplasma infection of peripheral blood mononuclear cells (PBMC) originating from female hyperprolactinemia patients. This study revealed that exogenous rhPRL as well as autologous sPRL from inactivated sera significantly restricted intracellular growth of Toxoplasma in PBMC cultures. Moreover, analysis of IL-10 production by PBMC infected with Toxoplasma and cultured in the presence of sPRL showed a positive correlation between sPRL concentration and the level of IL-10. The obtained results could indicate the possible protective action of PRL in a host organism infected with Toxoplasma and suggest that a significant increase in the serum PRL level, during pregnancy for instance, might significantly limit the risk of Toxoplasma spreading and could play an important role in natural protection against toxoplasmosis. The mechanism of inhibitory effect of PRL needs further detailed study.


An updated review on efficacy and benefits of sweet almond, evening primrose and jojoba oils in skin care applications.
Renewed consumer and industry interest in natural ingredients has led to a large growth of natural cosmetics. This has put pressure on formulation skills and product claims when it comes to using natural compounds. Taking a strategic and comprehensive approach in viewing natural ingredients, including natural oils, as 'active' ingredients rather than just providing for so-called 'natural' claims, aids both innovation and development. Given the ever-increasing consumer demand for natural ingredients, and more importantly the demand for effective natural ingredients including plant oils, it is important for the cosmetic industry to re-evaluate them in this context. The objectives of this review are to provide an update of three popular cosmetic plant oils - Sweet Almond, Evening Primrose and Jojoba - in terms of their cosmetic applications as 'active' ingredients. This review highlights the activity of these oils, in the management of dry skin, ageing skin, juvenile skin, atopic dermatitis, scalp conditions and their wider potential. Attention is given to formulation considerations where the content of these oils impacts product oxidation, skin penetration and stratum corneum homeostasis. Benefits of these oils have been well documented both pre-clinically and clinically. Historically, they have been used for hundreds if not thousands of years for their management and treatment of various skin and other ailments. Given the discrepancies in some clinical data presented for a variety of dermatoses, the importance of the choice of oil and how to formulate with them within the context of the epidermal barrier function, skin penetration and toxicity cannot be underestimated. Care should be taken in terms of the quality and stability of theses oils, as well as ensuring best formulation type, if the reported activities of these oils are to be achieved with consistency. Despite discrepancies in the literature and questionable study designs, it is clear that Sweet Almond, Evening Primrose and Jojoba oils do have skin care benefits for both adult and juvenile applications. They are effective ingredients for skin care preparations to strengthen stratum corneum integrity, recovery and lipid ratio. Nevertheless, further experimental data are required concerning the impact on stratum corneum physiology and structure.


"Dilute-and-shoot" triple parallel mass spectrometry method for analysis of vitamin D and triacylglycerols in dietary supplements.
A method is demonstrated for analysis of vitamin D fortified dietary supplements that eliminates virtually all chemical pretreatment prior to analysis, which is referred to as a "dilute-and-shoot" method. Three mass spectrometers, in parallel, plus a UV detector, an evaporative light-scattering detector (ELSD), and a corona charged aerosol detector (CAD) were used to allow a comparison of six detectors simultaneously. Ultraviolet data were analyzed using internal standard, external standard, and response factor approaches. The contents of gelcaps that contained 2,000 IU (50 μg) vitamin D(3) in rice bran oil, diluted to 100 mL, were analyzed without the need for lengthy saponification and extraction. Vitamin D(3) was analyzed using UV detection, extracted ion chromatograms, selected ion monitoring (SIM) atmospheric pressure chemical ionization mass spectrometry (APCI-MS), and two transitions of multiple reaction monitoring (MRM) APCI-MS. The internal standard, external standard, and response factor methods gave values of 0.5870 ± 0.0045, 0.5893 ± 0.0041, and 0.5889 ± 0.0045 μg/mL, respectively, by UV detection. The values obtained by MS were 0.6117 ± 0.0140, 0.6018 ± 0.0244, and 0.5848 ± 0.0146 μg/mL by SIM and two transitions of MRM, respectively. The triacylglycerols in the oils were analyzed using full-scan APCI-MS, electrospray ionization (ESI) MS, up to MS(4), an ELSD, and a CAD. The method proved to be very sensitive for vitamin D(3), as well as triacylglycerols (TAGs), allowing identification of intact TAGs containing fatty acids up to 28 carbons in length. LC-ESI-MS of glycerin polymers is also demonstrated.


Post-transfusion purpura due to HPA-1a immunization in a male patient: response to subsequent multiple HPA-1a-incompatible red-cell transfusions.
We report a male patient who developed post-transfusion purpura. Thrombocytopenia did not recur when intravenous IgG was given before the transfusion of platelet-depleted washed red-cell concentrates.


Insights into sensory hair cell regeneration from the zebrafish lateral line.
Loss of mechanosensory hair cells in the inner ear leads to loss of hearing. In humans this results in permanent deafness, as mammals are largely unable to regenerate hair cells. In contrast, zebrafish robustly regenerate hair cells in the sensory lateral line and ear and recent gene expression and time-lapse analyses of cell behaviors at the single cell level have greatly advanced our understanding of the mechanisms responsible for hair cell regeneration. In the lateral line, hair cell regeneration is controlled via dynamic interactions between Notch and Wnt/β-catenin signaling, and likely also between Fgf and the retinoic acid signaling pathways. Less is known about what initiates regeneration and we discuss potential pathways that may trigger proliferation after hair cell damage.


Isolation, purification and physicochemical properties of polysaccharide from fruiting body of Hericium erinaceus and its effect on colonic health of mice.
Hericium erinaceus was extracted with boiling water to obtain the crude polysaccharide (HECP) and refined polysaccharide (HERP). HERP was further purified using gradual ethanol precipitation to obtain five sub-fractions. Their physicochemical properties were evaluated, including chemical components, monosaccharide composition and molecular weight. Meanwhile, the effect of HERP on colonic health of mice was investigated by oral administration at dosages of 100, 200 and 400mg/kg of body weight (mg/kgbw), comparing with that of HECP. Results showed that the gradual ethanol precipitation could remarkably increase polysaccharide purity. HERP, HECP and the five purified fractions had different monosaccharide compositions, while the main monosaccharides were Glc and Gal. They all showed similar structure with amorphous appearance. Short-chain fatty acids productions in colonic and cecum contents, and feces of mice were increased in polysaccharide treated groups. Mice administrated with HERP at 400mg/kgbw showed significant reductions in pH values while obvious increases in moisture amounts. This study suggests that gradual ethanol precipitation is available for purification of polysaccharide from Hericium erinaceus and the extracted polysaccharide could improve colonic health.


BRAF V600E Gene Mutation Is Associated With Bilateral Malignancy of Papillary Thyroid Cancer.
Papillary thyroid cancer (PTC) is the most prevalent type of thyroid cancer, which is the most common type of endocrine malignancy. Stratification and personalized surgical management of PTC patients are the major challenges for thyroid surgeons. Though BRAF V600E gene mutation presents in 50-70% of PTCs, it is unclear whether BRAF V600E testing could contribute to clinical practice. Therefore, this study investigated the association between BRAF V600E mutation and clinicopathologic features of PTC to evaluate the benefit of BRAF V600E testing to clinical management of PTC. In total, 145 patients with PTC who underwent bilateral thyroid surgery between July 2016 and December 2016 were included in this study. BRAF V600E mutation status and other clinicopathologic features were evaluated using the resected samples obtained during the surgery. Bilateral PTC was found in 72.8% of the patients with BRAF V600E mutation, and in 42.0% of the patients without the mutation. In addition, the occurrence of BRAF V600E mutation was higher in cases with bilateral PTC (63.4%) than that in cases with unilateral PTC (42.3%). The difference observed above was statistically significant (P = 0.014 by chi-square test) and BRAF V600E mutation was significantly associated with the bilaterality of PTC (P = 0.0080 by logistic regression). Presence of BRAF V600E mutation has been found to be associated with bilaterality of PTC, suggesting that total or near total thyroidectomy should be considered for patients with the mutation.


An interesting case of aglossia-adactyly syndrome.
A case of aglossia-adactyly syndrome with a sagittal band between the floor of the mouth and the palate is reported. The literature concerning this case is briefly reviewed. This case is being presented for its extreme rarity.


Cell membrane damage by ultrasound at different cell concentrations.
Cell membrane damage by ultrasound was studied in human nucleated cells in vitro at various concentrations. Suspensions of human blood cells, cells of a human leukemic cell line (Reh) and mixtures of nucleated cells with erythrocytes were exposed to continuous ultrasound of 782 kHz at a SPTA intensity of 15 W/cm2. The surviving nucleated cells without membrane damage were counted on the basis of exclusion of ethidium bromide using a flow cytometer. At high cell concentrations as present in whole blood, we observed no cell death, whereas below 5 X 10(7) cells/ml most of the granulocytes, stimulated lymphocytes and Reh cells were damaged. The concentration threshold below which cells were damaged seemed not to depend on the size of the cells, rather on the concentration of particles in the suspension.


Validity of the Japanese core outcome measures index (COMI)-neck for cervical spine surgery: a prospective cohort study.
To investigate the psychometric properties of the Japanese version of the Core Outcome Measures Index-Neck (COMI-Neck) in patients undergoing cervical spine surgery. A total of 177 patients undergoing cervical spine surgery for spinal disorders from April to December 2017 were enrolled. Patient-reported outcomes (PROs) included EuroQOL, Neck Disability Index, and treatment satisfaction. To address whether the questionnaire's scores relate to other outcomes based on a predefined hypothesis, the correlations between the COMI-Neck and the other PROs were measured (Spearman's rank correlation coefficients). The minimum clinically important difference (MCID) of the COMI summary score was calculated using the receiver operating characteristic (ROC) curve with a 7-point Likert scale of satisfaction with the treatment results. To assess reproducibility, another group of 59 volunteers with chronic neck pain were asked to reply to the COMI-Neck twice with an interval of 7-14 days. The COMI summary score showed no floor or ceiling effects preoperatively or postoperatively. Each of the COMI domains and the COMI summary score correlated to the hypothesized extent with the scores of the reference questionnaires (ρ = 0.40-0.79). According to the ROC curve with satisfaction (including "very satisfied" and "satisfied"), the area under the curve and MCID of the COMI summary score were 0.78 and 2.1. The intraclass correlation coefficient and the minimum detectable change (MDC 95%) of the COMI summary score were 0.97 and 0.77. The Japanese version of the COMI-Neck is valid and reliable for Japanese-speaking patients with cervical spinal disorders.


Bilateral Acute Macular Neuroretinopathy (AMN) after COVID-19 and its Clinical Course.
Acute macular neuroretinopathy (AMN) is a rare disease entity. It is mainly observed in young women with a history of influenza-like infection or who have been taking oral contraceptives for several years. Patients typically describe subjective visual deterioration and mono- or bilateral paracentral relative scotomas. In some cases, funduscopic ophthalmic examination may reveal subtle sharply demarcated flat lesions of reddish-brown or orange colour in the macular region. Diagnosis is usually made by near-infrared fundus imaging which shows hyporeflective areas, and SD-OCT imaging which manifests changes in the outer retinal layers. In the following, three patient cases with bilateral AMN are described which occurred in direct temporal relationship to a recent SARS-CoV-2 infection.


Glycohistochemical characterization of vascular muscle cell destruction in CADASIL subjects by lectins, neoglycoconjugates and galectin-specific antibodies.
CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a type of small-artery stroke and vascular dementia-inducing pathology of the brain. In order to explain the molecular mechanisms behind the alterations to the blood vessels in CADASIL subjects, we scrutinized the expression of glycan and glycan-binding sites in the wall of vessels taken from five such subjects (vs. five control subjects matched for age and sex). Specimens were taken from the brain, heart, kidney, liver and lung. Although the main vessel lesions were observed in the tissues depending on the blood-brain barrier, alterations to systemic vessels were also observed despite the absence of any symptoms. The histochemical expression of a panel of 10 biotinylated neoglycoconjugates [Gal-beta(1-4)-D-Glc, Galbeta(1-3)GalNAc, alpha-D-GalNAc, beta-D-GalNAc, GalNAcalpha(1-3)-D-GalNAcalpha, GalNAcalpha(1-3)-D-GalNAcbeta, beta-D-Glc, alpha-D-Man, l-Fucose and D-Glcalpha(1-4)-D-Glc], eight plant lectins (PNA, MAA, SNA, DBA, WGA, ConA, GNA and UEA-1) and two antigalectin antibodies was monitored by means of semiquantitative and quantitative computer-assisted microscopy. The data show the altered histochemical binding of plant lectins, such as UEA-1 and ConA, in the vessel walls of CADASIL subjects. The present work, based upon staining by a panel of neoglycoconjugates, provides a biochemical characterization of the alteration of vessel walls in the brain compared to other organs including the heart, kidney, lung and liver in CADASIL as opposed to control subjects. These glycohistochemical results suggest a functional relevance of protein-carbohydrate interactions in this disease.


Self-conversion of drug resistant ventricular tachycardia by rapid atrial pacing.
A 523-year-old man with recurrent ventricular tachycardia two months post myocardial infarction is described. The tachycardia resulted in low output and heart failure at the time of presentation. Following electrocardioversion of ventricular tachycardia, sinus rhythm would last for only a few seconds, and ventricular tachycardia could not be terminated or prevented by drugs, nor by overdrive pacing. Over a 20-hour period, asynchronous right ventricular pacing at 30/min resulted in repeated random interruption of successive paroxysms of ventricular tachycardia, resulting in maintenance of sinus rhythm about 60 to 70% of the time. This produced marked hemodynamic improvement and a decrease in the frequency of paroxysms of tachycardia which, however, continued to recur once every few days. Despite their reduced frequency, these paroxysms continued to be resistant to drugs and had to be terminated by cardioversion. At this point it was discovered that rapid atrial pacing was able to terminate the patient's tachycardia reliably and reproducibly. A permanent right atrial externally activated radio frequency pacemaker device was inserted and over the ensuing eighteen-month period the patient self-terminated over fifty discrete episodes of ventricular tachycardia.


The effect of red cell transfusion on hemodialysis-related hypotension.
Blood pressures of 25 stable end-stage renal disease patients with chronic anemia (mean hemoglobin 5.9 g/dL) who had received 2 units of packed red cells during hemodialysis were studied. Three treatments preceding and three following the transfusion dialysis were compared. Twenty-eight hypotensive episodes preceded and 12 followed transfusion (P = .02). Intravenous sodium chloride used for hypotension declined from a mean of 20.4 to 10.2 mEq per dialysis (P = .01). The rate of decline in mean arterial pressure during dialysis was significantly slower following transfusion (P less than .01). Mean postdialysis weight fell from 62.0 kg before transfusion to 61.5 kg following transfusion (P less than .001). Thus, red cell transfusion raises intradialytic pressure and reduces the frequency of intradialytic hypotension.


Quercetin flavonoid and vitamin C recuperate kidney functions in potassium bromate-induced renal dysfunction in Wistar rats.
Studies into the functions and mechanisms of action of quercetin may be able to help dispel the negative effects of toxicants on renal toxicity due to its anti-inflammatory potential, as well as provide a simple, low-cost alternative for treating renal toxicity in developing nations. Therefore, the present study evaluated the ameliorative and renal protective activities of quercetin dihydrate in potassium bromate-induced, renal-toxic Wistar rats. Forty-five (45) mature female Wistar rats (180-200 g) were randomly grouped into nine (9) (n = 5). Group A served as general control. Nephrotoxicity was induced in groups B to I with the administration of potassium bromate. While group B served as a negative control, groups C-E received graded doses of quercetin (40, 60, and 80 mg/kg, respectively). Group F received 2.5 mg/kg/day of vitamin C, while groups G-I received vitamin C (2.5 mg/kg/day) and co-administration of a graded dose of quercetin (40, 60, and 80 mg/kg, respectively). Daily urine levels and final blood samples by retro-orbital techniques were collected for GFR, urea, and creatinine level assessment. The collected data were subjected to ANOVA and Tukey's post hoc test, and the results were presented as mean SEM with a p < 0.05 level considered significant. Body and organ weight and GFR were significantly reduced (p < 0.05), while serum and urine creatinine and urea were decreased in renotoxic animals. However, treatment with QCT reversed the renotoxic effects. We, therefore, concluded that quercetin administered alone or with vitamin C conferred renal protection by reversing KBrO3-induced renal toxicity in rats. Further studies to corroborate the present findings are recommended.


Skin care in nursing: A critical discussion of nursing practice and research.
Skin (self-)care is part of human life from birth until death. Today many different skin care practices, preferences, traditions and routines exist in parallel. In addition, preventive and therapeutic skin care is delivered in nursing and healthcare by formal and informal caregivers. The aim of this contribution is a critical discussion about skin care in the context of professional nursing practice. An explicit skin assessment using accurate diagnostic statements is needed for clinical decision making. Special attention should be paid on high risk skin areas, which may be either too dry or too moist. From a safety perspective the protection and maintenance of skin integrity should have the highest priority. Skin cleansing is the removal of unwanted substances from the skin surface. Despite cleansing efficacy soap, other surfactants and water will inevitably always result in the destruction of the skin barrier. Thousands of products are available to hydrate, moisturize, protect and restore skin properties dependent upon their formulation and the concentration of ingredients. These products intended to left in contact with skin exhibit several actions on and in the skin interfering with skin biology. Unwanted side effects include hyper-hydration and disorganization of lipid bilayers in the stratum corneum, a dysfunctional barrier, increased susceptibility to irritants and allergies, and increases of skin surface pH. Where the skin barrier is impaired appropriate interventions, e.g. apply lipophilic products in sufficient quantity to treat dry skin or protect the skin from exposure to irritants should be provided. A key statement of this contribution is: every skin care activity matters. Every time something is placed on the skin, a functional and structural response is provoked. This response can be either desired or undesired, beneficial or harmful. The choice of all skin care interventions in nursing and healthcare practice must be based on an accurate assessment of the skin and concomitant health conditions and on a clearly defined outcome. A standardized skin care and skin care product language is needed for researchers planning and conducting clinical trials, for reviewers doing systematic reviews and evidence-base summaries, for nurses and other healthcare workers to deliver evidence-based and safe skin care.


Angiotensin II as a cardiovascular risk factor.
A renin-angiotensin level that is inappropriately high for the systemic blood pressure and the state of sodium balance is now recognized to be one of the modifiable cardiovascular risk factors. Angiotensin acts both as a circulating hormone and as a locally acting paracrine/autocrine/intracrine factor. The adverse effects of angiotensin on the heart include the mechanical results of elevated resistance to the pumping function of the myocardium, as well as the effects of neurohumoral abnormalities on various cardiac structures. In addition, cardiac damage follows acute ischaemic injury or chronic energy starvation due to coronary artery disease, attributable to either mechanical obstruction (atherosclerotic and/or thrombotic) or functional stenosis (vasospasm). Activation of the renin-angiotensin system has several haemodynamic and humoral consequences, all of which may damage the myocardium. These include acute myocardial ischaemia, left-ventricular hypertrophy, arrhythmias, alterations in the coagulation-fibrinolysis equilibrium, increased oxidative stress, and pro-inflammatory activity. A brief review of some of the mechanisms by which activation of the renin-angiotensin system can inflict damage on the heart is presented.


Glp-1 Receptor Agonists Regulate the Progression of Diabetes Mellitus Complicated with Fatty Liver by Down-regulating the Expression of Genes Related to Lipid Metabolism.
Non-alcoholic fatty liver disease is mostly associated with diabetes mellitus. Dulaglutide is approved in type 2 diabetes as a hypoglycemic agent. However, its effects on liver fat and pancreatic fat contents are not evaluated yet. The objectives of the study were to evaluate the effects of dulaglutide on liver fat content, pancreatic fat content, liver stiffness, and liver enzyme levels. Patients have taken 0.75 mg subcutaneous dulaglutide each week for 4 weeks, then 1.5 mg weekly for 20 weeks plus standard treatment (metformin plus sulfonylurea and/or insulin; DS group, n = 25), or patients have taken standard treatment (metformin plus sulfonylurea and/or insulin) alone (ST group, n = 46) for type 2 diabetes management. Both groups reported a decrease in liver fat content, pancreatic fat content, and liver stiffness after interventions (p < 0.001 for all). After interventions, the DS group reported a higher decrease in liver fat content, pancreatic fat content, and liver stiffness than that of the ST group (p < 0.001 for all). After interventions, the DS group reported a higher decrease in body mass index than that of the ST group (p < 0.05). There were significant improvements in liver function tests, kidney function tests, lipid profiles, and blood counts after interventions (p < 0.05 for all). Both groups reported a decrease in body mass index after interventions (p < 0.001 for both). The DS group significantly decrease body mass index after interventions (p < 0.05) than the ST group.


Fentanyl for labour pain management: a scoping review.
Labour pain has been identified as an important reason for women to prefer caesarean section (CS). Fentanyl is one of the short acting opioids recommended by World Health Organization for pain relief during labour. This study aimed to identify and describe the available evidence on the use of fentanyl (monotherapy) for labour pain management by any routes of administration or regime. We included the records published until 31 December 2021 which reported administration of fentanyl to women with normal labour for labour pain relief. Data were extracted by one reviewer and checked by another reviewer using a standardised agreement form. We mapped and presented data descriptively in figure and tabular format. We included 51 records from 49 studies in our scoping review. The studies were conducted in 12 countries, mostly high-income countries. The study designs of the 51 included records were varied as follows: 38 (74.5%) experimental studies (35 randomised controlled trials and three quasi-experimental studies), and 12 (23.5%) observational studies (five retrospective cohort studies, four prospective cohort studies, two retrospective descriptive studies, and one descriptive study) and one qualitative study. Of the included records, six used intranasal fentanyl, five used subcutaneous fentanyl, 18 (35.3%) used intravenous fentanyl, 18 (35.3%) used intrathecal fentanyl, and nine used epidural fentanyl. Many records compared fentanyl with another analgesic agent while five records (9.8%) had no comparison group and seven records (13.7%) compared with no analgesia group. The doses of fentanyl varied by routes, study and the requirement depended on the women. Pain assessment was the most frequent outcome measure presented in the records (78.4%). Only nine records (17.6%) investigated women's satisfaction about labour pain relief using fentanyl and seven records (13.7%) reported the effect of fentanyl on breastfeeding. The most common reported neonatal outcomes were foetal heart rate (33 records, 64.7%) and Apgar score (32 records, 62.7%). There is limited primary evidence especially randomised controlled trials to evaluate the effectiveness and harms of different routes of fentanyl in low- or middle-income countries. There is a need for high-quality research to establish the most effective route of fentanyl and associated effects for evidence-based international guidelines.


Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction.
A method was developed for the synthesis of α-alkyl, α-aryl-bislactim ethers in good to excellent yields and high diastereoselectivities, consisting of a facile one-pot procedure in which the aryl group is introduced by means of a nucleophilic addition to benzyne and the alkyl group by alkylation of a resultant benzylic anion. Hydrolysis of the sterically less hindered adducts gave the corresponding quaternary amino acids with no racemization, whereas hydrolytic ring opening gave the corresponding valine dipeptides from bulkier bislactims.


Giant aneurysm of left circumflex artery branch with fistula to the coronary sinus: a case report.
Aneurysm of a coronary artery branch with a fistula is extremely rare. Here, we present a case of giant aneurysm of the left circumflex artery branch with a fistula to the coronary sinus treated successfully with aneurysmectomy. A 58-year-old woman was referred to our hospital due to an abnormal pericardial mass found by multidetector computed tomography. Imaging examination revealed a dilated left circumflex artery branch with a 30-mm aneurysm. Coronary angiography confirmed a left circumflex artery branch aneurysm with a fistula to the coronary sinus. As percutaneous occlusion of the aneurysm by catheterization was considered unsuccessful, the aneurysm was resected, and the fistula was occluded surgically with excellent outcome. Pathological examination suggested that congenital factors may have contributed to the development of the aneurysm. Computed tomography showed no recurrence of the aneurysm at 1-year postoperative follow-up. We presented a case of giant aneurysm of the left circumflex artery branch with a fistula to the coronary sinus. This is the first report of the combination of a giant coronary artery branch aneurysm with a fistula to the coronary sinus. Surgical aneurysmectomy should be considered in such cases to avoid fatal aneurysmal complications.


Blocking effects of OPC-21268 and OPC-31260 (vasopressin V1- and V2-receptor antagonists) on vasopressin-induced constrictions in isolated, perfused dog femoral arteries.
Using a perfusion technique of isolated vessels, constrictor responses to vasopressin (VP) and norepinephrine (NE) were investigated in perfused dog femoral arteries. Both OPC-21268, a selective V1-antagonist, and OPC-31260, a selective V2-antagonist, significantly shifted the VP-induced dose response curves to the right without influencing the NE-induced ones. The blocking effects of OPC-31260 were much greater than those of OPC-21268, suggesting that there may probably be functional V1- and V2-receptors in isolated dog femoral arteries that mediate vasoconstriction.


Studies on the homing of Mycobacterium-sensitized T lymphocytes to the synovium during passive adjuvant arthritis.
The migration of intravenously administered adjuvant sensitized T lymphocytes to the knee synovium of recipient rats undergoing passive adjuvant arthritis has been followed. Using fluorescein isothiocyanate (FITC)-labeled adjuvant-sensitized T cells and anticollagen IgG, the present studies demonstrate the presence of fluorescent cells in the inflamed knee synovium of recipient rats undergoing passive arthritis. Proliferation studies indicate that synovial cells from these rats respond to Mycobacterium tuberculosis (MT). Since cross-reactivity between Mycobacterial antigens and cartilage proteoglycans has been previously demonstrated, it is suggested that adjuvant-sensitized T cells that are injected into naive rats migrate to the synovium, proliferate in response to cartilage proteoglycan, and initiate passive arthritis.