Glucocorticoid use represents a risk factor for central serous chorioretinopathy: a prospective, case-control study.
To evaluate whether exposure to glucocorticoids represents a risk factor for the development of central serous chorioretinopathy (CSCR). Prospective, case-control study. Thirty-eight consecutive patients with acute CSCR were asked to answer a specific questionnaire regarding the use of glucocorticoids, in any form, during the last month before the onset of the symptoms. An age- and sex-matched control group was also recruited. It consisted of patients attending the outpatient department for a condition other than CSCR, who were asked to answer the same questionnaire. Use of glucocorticoids was recorded in 11 of 38 patients (28.9%) with CSCR; 8 of them were men and 3 women. In the control group, use of glucocorticoids was recorded in 2 of 38 patients (5.2%), 1 man and 1 woman. The difference between the two groups is statistically significant (odds ratio=7.33, 95% CI=1.49-35.85, P=0.006). In this prospective, case-control study, we found that glucocorticoid use represents a risk factor for the development of CSCR.


Traumatic rupture of the pulmonary artery.
Traumatic rupture of the main pulmonary artery in a surviving patient is very rare. The case history of a 37-year-old man who sustained blunt chest trauma in a motor vehicle accident is presented. A persistent, bloody right pleural effusion led to the diagnosis of a ruptured right main pulmonary artery, which was surgically repaired using cardiopulmonary bypass. Points of diagnostic interest and therapeutic decision making are discussed.


Evaluating composite health measures using Rasch modelling: an illustrative example.
The purpose of the present article is to elucidate the opportunities provided by Rasch modelling in epidemiology and public health research in order to evaluate composite measures of health. The article gives a review of Rasch modelling in conjunction with illustrative examples based on adolescent survey data. The article demonstrates how the Rasch-model enables examinations of the way items work across different samples/subgroups, e.g., detection of possible differential item functioning. It is concluded that Rasch modelling may serve as a useful tool in the evaluation and the development of composite health measures intended to be used in epidemiology and public health research.


Erratum: Author Correction: Improved Brassica rapa reference genome by single-molecule sequencing and chromosome conformation capture technologies.
[This corrects the article DOI: 10.1038/s41438-018-0071-9.].


Primary prostatic squamous cell carcinoma.
Primary prostate squamous cell malignancies are rare and very aggressive. A 65-year-old man presented to our institution with clinical and radiographic findings concerning for advanced prostatic malignancy. Surgical pathology of the tumor revealed poorly differentiated carcinoma with squamous differentiation, and histopathological markers were positive for markers of squamous differentiation negative for all urothelial and prostatic markers.


[Scale-up of the fermentation of Leptospira interrogans canicola canicola for the production of vax-SPIRAL vaccine].
The operational conditions for the production of vaccine vax-SPIRAL were established at the scale of 100 L. It was concluded that it should be carried out with an air flow of 10 L/min (0.1 vvm) and without mechanical agitation.


Muscle glycogen synthesis and disposition of infused glucose in humans with reduced rates of insulin-mediated carbohydrate storage.
Six men with a low rate of insulin-stimulated, non-oxidative carbohydrate disposal (storage) and six with a high storage rate were recruited for study of the fate of insulin-stimulated glucose uptake. [3-3H]glucose was infused before and during a 4-h hyperinsulinemic euglycemic clamp procedure in a dosage regimen designed to maintain a constant specific activity. From the disposition of label, the rate of insulin-mediated glucose incorporation into glycogen in the low-storage subjects was one-fourth that of the high-storage subjects (P less than .02). The insulin-mediated increase in muscle glycogen synthase activity in the low-storage subjects was one-fourth that of the high-storage subjects (P less than .05), suggesting the possibility of a causal relationship. In the high-storage but not the low-storage subjects, the rate of glycolysis inferred from the appearance of metabolized tritium in body water exceeded the carbohydrate oxidation rate (P less than .002). This suggests that in these subjects there is a significant fraction of glycolysis that is not oxidized and that this component of carbohydrate metabolism therefore contributes to storage.


Diagnostic utility of urethral smears in predicting urethral chlamydia in HIV-infected men.
We collected data from 218 HIV-infected men to assess the usefulness of the urethral smear and symptoms in predicting Chlamydia trachomatis infection. Prevalence of urethral chlamydia was 9%. A polymorphonuclear leucocyte (PMNL) count>or=5 was 73% sensitive and 71% specific for C. trachomatis infection. Adjusted odds ratio for risk of chlamydial infection was significant for urethral irritation (7.48; 1.54-36.4), a PMNL count of 20 or more (9.83; 2.52-8.4) and a PMNL count of 5-19 (4.10; 1.34-12.5). We had to perform 50 urethral smears in HIV-positive men without symptoms to treat one case of C. trachomatis at the time of visit. Findings suggest that the presence of symptoms, in particular urethral irritation may be associated with chlamydial urethritis and that the higher the urethral PMNL count, the more likely it is for C. trachomatis to be detected. The findings in this study also lend further support to recent guidelines that urethral microscopy is not useful in asymptomatic men and hence should be abandoned.


The return of the house call: the role of internet-based interactivity in bringing health information home to older adults.
This study provides qualitative insight into how older adults are using the Internet for health communication. The research is framed with theory from several disciplines, including health and interactive communication, as well as related theoretical models. Data from focus groups was used to develop a model of seniors' online health interactions. Three primary themes that emerged in focus groups form the key elements of the model: the health situation, health information, and the medical field. Implications are suggested for advertising and marketing on the Internet, health information providers, and academic researchers in these areas.


Conventional and advanced MRI features of pediatric intracranial tumors: posterior fossa and suprasellar tumors.
In this article, we review the most common posterior fossa and suprasellar intracranial neoplasms in the pediatric population. We briefly discuss basic MRI concepts used in the initial evaluation of a pediatric brain tumor and then discuss sophisticated MRI techniques that give insight into the physiology and chemical makeup of these tumors to help the radiologist make a more specific diagnosis. Diagnosis and treatment of pediatric CNS tumors necessitate a multi-disciplinary approach and require expertise and diligence of all parties involved. Imaging is an essential component has evolved greatly over the past decade. We are becoming better at making a preoperative diagnosis of that tumor type, detecting recurrence, and guiding surgical management to avoid injury to vital brain structures.


Mapping Brain Structure Variability in Chronic Pain: The Role of Widespreadness and Pain Type and Its Mediating Relationship With Suicide Attempt.
Chronic pain affects nearly 20% of the U.S. It is a leading cause of disability globally and is associated with a heightened risk for suicide. The role of the central nervous system in the perception and maintenance of chronic pain has recently been accepted, but specific brain circuitries involved have yet to be mapped across pain types in a large-scale study. We used data from the UK Biobank (N = 21,968) to investigate brain structural alterations in individuals reporting chronic pain compared with pain-free control participants and their mediating effect on history of suicide attempt. Chronic pain and, more notably, chronic multisite pain was associated with, on average, lower surface area throughout the cortex after adjusting for demographic, clinical, and neuropsychiatric confounds. Only participants with abdominal pain showed lower subcortical volumes, including the amygdala and brainstem, and lower cerebellum volumes. Participants with chronic headaches showed a widespread thicker cortex compared with control participants. Mediation analyses revealed that precuneus thickness mediated the relationship of chronic multisite pain and history of suicide attempt. Mediating effects were also identified specific to localized pain, with the strongest effect being amygdala volume in individuals with chronic abdominal pain. Results support a widespread effect of chronic pain on brain structure and distinct brain structures underlying chronic musculoskeletal pain, visceral pain, and headaches. Mediation effects of regions in the extended ventromedial prefrontal cortex subsystem suggest that exacerbated negative internal states, negative self-referencing, and impairments in future planning may underlie suicidal behaviors in individuals with chronic pain.


Biases arising from linked administrative data for epidemiological research: a conceptual framework from registration to analyses.
Linked administrative data offer a rich source of information that can be harnessed to describe patterns of disease, understand their causes and evaluate interventions. However, administrative data are primarily collected for operational reasons such as recording vital events for legal purposes, and planning, provision and monitoring of services. The processes involved in generating and linking administrative datasets may generate sources of bias that are often not adequately considered by researchers. We provide a framework describing these biases, drawing on our experiences of using the 100 Million Brazilian Cohort (100MCohort) which contains records of more than 131 million people whose families applied for social assistance between 2001 and 2018. Datasets for epidemiological research were derived by linking the 100MCohort to health-related databases such as the Mortality Information System and the Hospital Information System. Using the framework, we demonstrate how selection and misclassification biases may be introduced in three different stages: registering and recording of people's life events and use of services, linkage across administrative databases, and cleaning and coding of variables from derived datasets. Finally, we suggest eight recommendations which may reduce biases when analysing data from administrative sources.


An on-line microcomputer program for the monitoring of physiological variables during rest and exercise.
This paper describes a microcomputer system for the on-line display of physiological variables such as: lung ventilation, tidal volume, respiratory frequency, oxygen consumption, heart rate, oxygen pulse, respiratory exchange ratio, grams of fat and carbohydrate metabolised, mean skin temperature, rectal temperature and mean body temperature. The program has been written in Pascal. The modular nature of this language facilitates modification of the program to make it compatible with a variety of hardware and peripherals.


Decreased myocardial and renal content of 3',5'-AMP in genetically hypertensive rats: effects of PGE2 and PGF2 alpha.
Levels of c-AMP in heart and kidney of genetically hypertensive rats (SHR) were significantly lower than in normotensive Wistar animals. PGE2, 10 microgram/kg ip markedly increased the concentration of c-AMP in heart and kidney of SHR animals, but was without effect on this cyclic nucleotide content in normotensive controls. PGF2, in doses up to 100 microgram/kg, did not influence the concentrations of c-AMP in heart and kidney of SHR animals. Alterations in adenylate cyclase--c-AMP system in genetic hypertension are discussed.


Soft-tissue interposition as a possible cause of scaphoid non-union.
Two cases of dorsal trans-scaphoid perilunar dislocation are reported, in which the fracture was found, at operation, to contain interposed ligament. It is recommended that such fractures be explored unless perfectly reduced, and that percutaneous pinning of the reduced fracture may be inadequate treatment.


Implementing a Tailored Psychosocial Distress Screening Protocol in a Head and Neck Cancer Program.
Psychosocial distress is common among patients with head and neck cancer (HNC) and is associated with poorer quality of life and clinical outcomes. Despite these risks, distress screening is not widely implemented in HNC care. In this study, we investigated the prevalence of psychosocial distress and its related factors in routine care of patients with HNC. Data from medical records between September 2017 and March 2020 were analyzed. Psychosocial distress was measured by the National Comprehensive Cancer Network's Distress Thermometer (DT), and a modified HNC-specific problem list; depression and anxiety were assessed using the Patient Health Questionnaire-4. Descriptive statistics and logistic regression were conducted to report prevalence of distress, depression and anxiety, and factors associated with clinical distress. Implementation outcomes, including rates of referrals and follow-up for distressed patients, are also reported. Two hundred and eighty seven HNC patients completed the questionnaire (age 64.3 ± 14.9 years), with a mean distress score of 4.51 ± 3.35. Of those, 57% (n = 163) reported clinical distress (DT ≥ 4). Pain (odds ratio [OR] = 3.31, 95% CI = 1.75-6.26), fatigue (OR = 2.43, 95% CI = 1.1.7-5.05), anxiety (OR = 1.63, 95% CI = 1.30-2.05), and depression (OR = 1.51, 95% CI = 1.04-2.18) were significantly associated with clinical distress (P < .05). Of patients identified as distressed, 79% received same-day psychosocial evaluation. Clinical distress was identified in 57% of patients who completed the questionnaire, suggesting that an ultra-brief psychosocial screening protocol can be implemented in routine ambulatory oncology care, and identifies patients whose distress might otherwise go unrecognized. 4 Laryngoscope, 132:1600-1608, 2022.


Monocyte function in cervical carcinoma: plasma inhibitor of monocyte chemotaxis.
Blood monocyte function was tested in 43 untreated patients with carcinoma of the cervix (stages Ib to IIIb) and 50 age-matched controls. Monocyte counts, adhesion to glass, spreading on glass, phagocytosis and killing of Candida albicans, and chemotaxis under agarose were not significantly different between the patient and control groups. In 65% of a further series of 17 patient/control pairs, the plasma of cervical carcinoma patients was shown to contain a cell-directed inhibitor of monocyte chemotaxis. The accumulated evidence indicates that production of such factors by malignant tumors is an important mechanism in counteracting mononuclear phagocyte defense.


Cellular cholesterol homeostasis in vascular endothelial cells.
Atherosclerosis is a disease of blood vessel walls that is thought to be initiated as a reaction of insults to the endothelium. The complex sequence of cellular events that begins with focal inflammation leads to the accumulation of leukocytes in the subendothelial layer and unrestricted uptake of oxidized lipoproteins by macrophages and smooth muscle cells, leading to foam cell formation. Vascular endothelial cells do not undergo the foam cell transformation and do not accumulate cholesterol in atherosclerotic plaques to the same extent as macrophages or smooth muscle cells. However, vascular endothelial cells express receptors for oxidized lipoproteins, and have the biochemical pathways for sterol synthesis and receptor-mediated endocytosis of lipoproteins. Data from the authors' laboratory show that high density lipoproteins but not lipid-free apolipoprotein A-I promote cellular cholesterol efflux in human umbilical vascular endothelial cells and human aortic endothelial cells. Gene expression microarrays were used to examine the differential expression of genes after cholesterol loading. While sterol regulatory element-binding protein-sensitive genes were downregulated, the authors identified a novel transporter, the ATP-binding cassette G1 (ABCG1) to be highly expressed in response to both cellular cholesterol loading and stimulation with the liver X receptor agonist 22-hydroxycholesterol. The ABCA1 gene and protein, the major modulator of cellular cholesterol efflux in macrophages and in peripheral and hepatic tissues, are only weakly expressed in human umbilical vascular endothelial cells and human aortic endothelial cells. These data suggest that endothelial cells maintain cholesterol homeostasis by downregulating cholesterol synthesis and low density lipoprotein receptors and by a cellular cholesterol efflux mechanism onto low-affinity but high-capacity high density lipoproteins. The role of ABC-type transporters, including ABCG1, requires further examination.


Bioethanol production involving recombinant C. thermocellum hydrolytic hemicellulase and fermentative microbes.
The enhancement of the biomass productivity of Escherichia coli cells harbouring the truncated 903 bp gene designated as glycoside hydrolase family 43 (GH43) from Clostridium thermocellum showing hemicellulase activity along with its further use in simultaneous saccharification and fermentation (SSF) process is described. (Phosphoric acid) H(3)PO(4)-acetone treatment and ammonia fibre expansion (AFEX) were the pretreatment strategies employed on the leafy biomass of mango, poplar, neem and asoka among various substrates owing to their high hemicellulose content. GH43 showed optimal activity at a temperature of 50 °C, pH 5.4 with stability over a pH range of 5.0-6.2. A 4-fold escalation in growth of the recombinant E. coli cells was observed when grown using repeated batch strategy in LB medium supplemented with glucose as co-substrate. Candida shehatae utilizing pentose sugars was employed for bioethanol production. AFEX pretreatment proved to be better over acid-acetone technique. The maximum ethanol concentration (1.44 g/L) was achieved for AFEX pretreated mango (1%, w/v) followed by poplar with an ethanol titre (1.32 g/L) in shake flask experiments. A 1.5-fold increase in ethanol titre (2.11 g/L) was achieved with mango (1%, w/v) in a SSF process using a table top 2-L bioreactor with 1 L working volume.


Maternal stress or sleep during pregnancy are not reflected on telomere length of newborns.
Telomeres play an important role in maintaining chromosomal integrity. With each cell division, telomeres are shortened and leukocyte telomere length (LTL) has therefore been considered a marker for biological age. LTL is associated with various lifetime stressors and health-related outcomes. Transgenerational effects have been implicated in newborns, with maternal stress, depression, and anxiety predicting shorter telomere length at birth, possibly reflecting the intrauterine growth environment. Previous studies, with relatively small sample sizes, have reported an effect of maternal stress, BMI, and depression during pregnancy on the LTL of newborns. Here, we attempted to replicate previous findings on prenatal stress and newborn LTL in a sample of 1405 infants using a qPCR-based method. In addition, previous research has been expanded by studying the relationship between maternal sleep quality and LTL. Maternal prenatal stress, anxiety, depression, BMI, and self-reported sleep quality were evaluated with self-reported questionnaires. Despite sufficient power to detect similar or even considerably smaller effects than those previously reported in the literature, we were unable to replicate the previous correlation between maternal stress, anxiety, depression, or sleep with LTL. We discuss several possible reasons for the discrepancies between our findings and those previously described.


Primary Care Management of Asthma Exacerbations or Attacks: Impact of the COVID-19 Pandemic.
The COVID-19 pandemic has brought a renewed focus on appropriate management of chronic respiratory conditions with a heightened awareness of respiratory symptoms and the requirement for differential diagnosis between an asthma attack and COVID-19 infection. Despite early concerns in the pandemic, most studies suggest that well-managed asthma is not a risk factor for more severe COVID-related outcomes, and that asthma may even have a protective effect. Advice on the treatment of asthma and asthma attacks has remained unchanged. This article describes some challenges faced in primary care asthma management in adults and in teenagers, particularly their relevance during a pandemic, and provides practical advice on asthma attack recognition, classification, treatment and continuity of care. Acute attacks, characterised by increased symptoms and reduced lung function, are often referred to as exacerbations of asthma by doctors and nurses but are usually described by patients as asthma attacks. They carry a significant and underestimated morbidity and mortality burden. Many patients experiencing an asthma attack are assessed in primary care for treatment and continuing management. This may require remote assessment by telephone and home monitoring devices, where available, during a pandemic. Differentiation between an asthma attack and a COVID-19 infection requires a structured clinical assessment, taking account of previous medical and family history. Early separation into mild, moderate, severe or life-threatening attacks is helpful for continuing good management. Most attacks can be managed in primary care but when severe or unresponsive to initial treatment, the patient should be appropriately managed until transfer to an acute care facility can be arranged. Good quality care is important to prevent further attacks and must include a follow-up appointment in primary care, proactive regular dosing with daily controller therapy and an understanding of a patient's beliefs and perceptions about asthma to maximise future self-management.


The effects of valsartan on scar maturation in an experimental rabbit ear wound model.
In our study, we aimed to search and compare the effects of valsartan and enalapril on the pathological scar formation on the basis of histomorphological parameters. Nine New Zealand albino male rabbits, which were divided into three groups, were included in the study. A previously described rabbit ear wound model was used. Enalapril was administered 0.75 mg/kg/day on the first group and valsartan was administered 10 mg/kg/day on the second group for 40 days. The third group was the control group. Results were evaluated on the 40th day with scar elevation index calculation and histological studies. Histological studies were done by using Hematoxylin-eosin, Masson trichrome and Sirius Red stains. Enalapril and valsartan groups were both significantly effective on the prevention of pathological scar formation when compared to the control group in terms of fibroblast count, capillary count, type 1/3 collagen ratio, collagen organization, and epithelial thickness. There was no significant difference between the enalapril and control group on the scar elevation index. Valsartan group was more efficient than the enalapril group on the reduction of fibroblast count and epithelial thickness. Both Valsartan and Enalapril are found to be effective for the prevention of pathological scar formation.


Bacterial contamination of tissue allografts - experiences of the donor tissue bank of Victoria.
The aim of this study is to report the experience of the Donor Tissue Bank of Victoria with bacteria isolated from musculoskeletal, skin and cardiac allografts retrieved from cadaveric donors. The results of all quality control samples for bacterial culture, taken during retrieval and processing of allografts at the DTBV for a 12 month period, were extracted and analysed. It was found that 15.7% of skin, 15.1% of heart valves and 5.8% of musculoskeletal samples had positive culture results. The number and types of organisms isolated varied with tissue type. The most commonly isolated organisms were Staphylococcus species (including S. aureus). The identity of the isolate and the number of positive specimens from the same donor were considerations in the decision concerning the suitability of tissue for subsequent implantation.


Therapeutically-rational exchange (T-REX) of Gerbich-negative red blood cells can be evaluated in Papua New Guinea as "a rescue adjunct" for patients with Plasmodium falciparum malaria.
"Conventional exchange transfusion"-that delivers nondescript "standard issue" units of red blood cells (RBCs)-is used worldwide to rescue dying Plasmodium falciparum (Pf) malaria patients. Recently, exchanging special malaria-resistant RBCs (T-REX) has been recommended to prevent random delivery of malaria-susceptible RBCs that promote Pf infection. Fortunately, Papua New Guinea (PNG) is well positioned to help optimize exchange as "a rescue adjunct" because (a) Gerbich-negative (GN) RBCs that resist Pf invasion are prevalent in PNG; (b) with international support, PNG has conducted outstanding malaria research; (c) PNG's scientists feel studies of GN RBCs can advance malaria therapeutics; and (d) with blood-bank support, evaluating exchange of GN RBCs is feasible in PNG. An exchange-transfusion study of GN RBCs might attract international sponsorship given the threat of expanding drug-resistance as well as growing recognition that advancing transfusion medicine and expanding blood donation could especially help Pf-infected children-immediately.


Preparation of 11C-labelled Raclopride, a new potent dopamine receptor antagonist: preliminary PET studies of cerebral dopamine receptors in the monkey.
A new dopamine receptor antagonist, Raclopride (S-(-)-3,5-dichloro-N-[(1-ethyl-2-pyrrolidinyl)]methyl-2-hydroxy- 6-methoxybenzamide, FLA 870) (1), has been labelled using [11C]ethyl iodide for alkylation of the nitrogen of the pyrrolidine ring in the corresponding secondary amine (5). The synthesis of 5 and an efficient method for the preparation of [11C]ethyl iodide are described. The 11C-labelled FLA 870 (1) was purified by HPLC and then used in positron emission tomography to visualize the dopamine receptor-rich areas of the monkey brain. The images obtained show selective accumulation of FLA 870 in striatum and a 10-fold separation between the binding to caudate vs cerebellum.


National trends in metabolic syndrome among adults in Mongolia from three cross-sectional surveys in 2009, 2013 and 2019.
Metabolic syndrome (MetS) may increase the risk of cardiometabolic diseases. The study aimed to estimate the proportion and associated factors of MetS among individuals (≥15 years) across three cross-sectional surveys in 2009, 2013 and 2019 in Mongolia. Cross-sectional data were analysed from 6,321 individuals (15-64/69 years, median age = 42 years) that participated in the 2009, 2013 or 2019 Mongolia STEPS surveys, and had complete MetS (harmonized definition) measurements. Almost two in five participants (35.6%) had MetS, 33.3% in 2009, 35.3% in 2013, ad 37.0% in 2019 (p-for trend 0.023). In adjusted logistic regression analyses, older age was associated with MetS in 2009 and in 2019, male sex and higher education were associated with MetS in 2013, and urban residence was associated with MetS in 2009. Current tobacco use was associated with MetS in 2009 and 2019, moderate or high physical activity was protective against MetS in 2013 and 2019, while general overweight and obesity increased the odds of MetS in 2009, 2013, and 2019. The study showed that almost two in five adults were identified as having MetS, which significantly increased from 2009 to 2019, and that several predictors of MetS were found.


Contributions of unfrozen fraction and of salt concentration to the survival of slowly frozen human erythrocytes: influence of warming rate.
The general belief is that slow freezing injury is either the result of exposure to high salt concentrations or the result of excessive cell shrinkage. Increased salt concentration arises as increasing amounts of pure ice precipitate out of solution during freezing and cause the liquid-filled channels in which the cells are sequestered to dwindle in size. Cell shrinkage is an osmotic response to the concentration of external solutes. The consensus has been that the injury is related to the composition of the solution in these channels and not to the amount of residual liquid. Ordinarily, salt concentration and the amount of liquid in the unfrozen channels are reciprocally related; but they can be separated within limits by varying the total concentration of solutes in the suspending medium while holding the mass ratio of additive to salt constant, and by then slowly freezing samples to various subzero temperatures, chosen to produce various molalities of salt, while holding the unfrozen fraction constant, or vice versa. We have recently reported (9) that when human red cells are frozen under these conditions and thawed rapidly, survival is more dependent on the unfrozen water fraction than it is on the salt concentration in that fraction. The present work compares these results with those obtained with slow thawing. While the general conclusion remains unaltered, slowly thawed cells were able to survive the freezing of a higher fraction of extracellular water than were rapidly thawed cells. Calculations were made of the changes in cell volume during the equilibration with glycerol and the subsequent freezing involved in these experiments. Cell size and cell solute concentration were found to be independent of the fraction of unfrozen extracellular water, but cell survival was strongly dependent on that fraction. If applicable to other than human red cells, this finding is likely to require major modifications in current views of slow-freezing injury and its prevention.


Simple and rapid gas-liquid-solid chromatographic analysis of trace concentrations of acetaldehyde in urban air.
A simple and rapid gas-liquid-solid chromatographic method for the analysis of trace concentrations of acetaldehyde in urban air (in the Nagoya area) was developed, with the use of cold trapping with liquid oxygen. In the analytical main column the conditions were: stationary phase, Triton X-100 (0.4%); support, Carbopack B (60-80 mesh); glass column, 1.5 m X 3 mm I.D.; column temperature, 75 degrees; carrier gas (nitrogen) flow-rate, 50-80 ml/min. In the cold trapping pre-column the conditions were: stationary phase, Tris (2-cyanoethoxy) propane (25%); support, Shimalite (AW, DMCS) (60-80 mesh); glass column, 31 cm X 4 mm I.D.; operating temperature for the trapping, -183 degrees (liquid oxygen temperature); operating temperature for injection of the condensed sample into the gas chromatograph, increased from -183 degrees to +100 degrees for 2 min. The acetaldehyde peak was identified by the disappearance method with a 2,4-dinitrophenylhydrazine-orthophosphoric acid-glass beads column. The ranges and average concentrations of acetaldehyde detected in 13 urban air samples were 1.5-9.6 and 4.7 ppb, respectively.


Is There a Link between Vomeronasalitis and Aggression in Stable Social Groups of Female Pigs?
The vomeronasal organ (VNO) is a bilateral chemosensory structure strongly involved in animal behaviour, thanks to its sensory epithelium (VNSE) that detects pheromones. Experimental VNO lesions can impair social, reproductive and maternal behaviour, while feline spontaneous vomeronasalitis has been associated with aggression. This study aimed to describe vomeronasalitis in farm pigs and explore its association with intraspecific behavioural alterations. Using 38 six-month-old pigs, the skin lesion score based on Welfare Quality® protocols was obtained during the fattening period. The seventy-six VNOs from these pigs were stained in haematoxylin-eosin for histological examinations. VNSE inflammation was classified considering its intensity. Skin lesions data were compared to vomeronasalitis. There were 34% of pigs that showed unilateral VNSE inflammation, while 66% were bilaterally affected. The mean ± SD number of skin lesions/animal was 4.4 ± 2.82, and 34% of pigs scored 1 (moderately wounded animals) at least once during the fattening period. Statistical analysis showed an association between bilateral vomeronasalitis and skin lesion score (p < 0.05) and between bilateral moderate vomeronasalitis and skin lesions number (p < 0.01). This is the first report linking vomeronasalitis to social life in farm animals. Considering the role of social life in animal welfare, our data opens a research field linking pathology to animal behaviour.


Evaluation of theophylline overdoses and toxicities.
Patients presenting with elevated theophylline concentrations and manifestations of toxicity may be categorized as being either overdose or iatrogenic toxic. In addition to severe cardiac and neurologic toxicities, such as arrhythmias and seizures, OD patients probably require monitoring for manifestation of gastrointestinal hemorrhage, electrolyte abnormalities, and hypotension. The possibility of a delayed peak theophylline concentration after sustained release product ingestion must be considered. Patients with initial serum concentrations of less than 60 mg/L may receive a single dose of oral activated charcoal and have repeat concentrations drawn to ensure the avoidance of continued absorption. The presence of a serum concentration exceeding 60 mg/L in OD patients warrants initiation of elimination-enhancing modalities. Oral activated charcoal is the fastest and most readily available. Multiple-dose oral activated charcoal should be given until serum theophylline concentrations of 60 mg/L or less are reached. Cardiac monitoring and seizure precautions are recommended. Admission to the intensive care unit should be considered when serum concentrations do not decline after several hours of charcoal therapy or when seizures and severe cardiovascular manifestations occur. Patients having initial concentrations exceeding 100 mg/L and/or rapidly rising concentrations 100 mg/L over baseline values should be considered as candidates for CHP or RHP if available. If both CHP and RHP are unavailable or will be excessively delayed, HD is a reasonable alternative. Patients on chronic theophylline therapy (IA patients) presenting with symptoms of toxicity must be evaluated carefully. If serum concentrations are less than 20 mg/L, short-term observation or a reduction in dose should be sufficient. Patients with concentrations between 20 and 60 mg/L should be candidates for seizure precautions and cardiac monitoring. Oral activated charcoal may be started and continued until levels are below 20 mg/mL. Patients with concentrations in excess of 60 mg/L require intensive monitoring (including seizure precautions and cardiac monitoring) as well as initiation of MOAC or CHP/RHP as situation, availability, and patient tolerance dictate. Again, HD may be a reasonable alternative if the others are unavailable or contraindicated.


Acute ischemic stroke imaging: a practical approach for diagnosis and triage.
Ischemic stroke is a prevalent disease with significant associated morbidity and healthcare costs. There are currently effective intravenous and endovascular therapies that have the potential to improve functional outcome when used in the appropriate patient population. The utilization of various imaging modalities has been shown to be crucial in identifying which patients may benefit from these therapies. Therefore, a thorough understanding of the role that imaging plays in guiding therapeutic decisions in acute ischemic stroke patients is important.


Effects of theta phase precessing optogenetic intervention on hippocampal neuronal reactivation and spatial maps.
As animals explore environments, hippocampal place cells sequentially fire at progressively earlier phases of theta oscillations in hippocampal local field potentials. In this study, we evaluated the network-level significance of theta phase-entrained neuronal activity in organizing place cell spike patterns. A closed-loop system was developed in which optogenetic stimulation with a temporal pattern replicating theta phase precession is delivered to hippocampal CA1 neurons when rats traversed a particular region on a linear track. Place cells that had place fields during phase precessing stimulation, but not random phase stimulation, showed stronger reactivation during hippocampal sharp-wave ripples in a subsequent rest period. After the rest period, place cells with place fields that emerged during phase precessing stimulation showed more stable place fields. These results imply that neuronal reactivation and stability of spatial maps are mediated by theta phase precession in the hippocampus.


A Systematic Review of Minimally Invasive Approaches to Uterine Fibroid Treatment for Improving Quality of Life and Fibroid-Associated Symptoms.
Improvement in symptom severity and quality of life (QoL) are critical concerns for women with fibroids as they evaluate treatment options. This systematic review analyzed available evidence regarding minimally invasive approaches to fibroid treatment and compared validated QoL and fibroid-associated symptom scores before and after treatment. A comprehensive search was conducted using PubMed, Embase, Cochrane Library, and Scopus from January 1990 to July 2020. English-language publications were included if they evaluated associations between minimally invasive approaches to fibroid treatment and QoL or fibroid-associated symptoms, and they used validated questionnaires before and after treatment. QoL or fibroid-associated symptom scores were compared and summarized for each minimally invasive approach. Thirty-seven studies were ultimately included in this review: 26 evaluating individual approaches and 11 which were comparative studies of minimally invasive approaches and surgical interventions. Radiofrequency ablation (RFA) and ultrasound-guided sclerotherapy (USGS) significantly improved overall QoL. Uterine artery embolization (UAE) and ultrasound-guided high-intensity frequency ultrasound (US-HIFU) improved overall QoL to a similar extent as surgical interventions. Twenty-eight studies assessed fibroid-associated symptoms with the Uterine Fibroid Symptoms Quality of Life Questionnaire (UFS-QoL). UAE, magnetic resonance imaging-guided high-intensity frequency ultrasound (MR-HIFU), US-HIFU, RFA, and percutaneous microwave ablation (PMWA) significantly decreased Symptom Severity Score by a range of 21 to 39 points (out of 100) at 6 months. Minimally invasive approaches to treat fibroids were effective alternatives to surgical interventions for improving quality of life, fibroid-associated symptoms, and pain. Outcomes among minimally invasive approaches were similar, presenting patients with numerous options for fibroid treatment.


Prediction of glomerular filtration rate from serum creatinine concentration in advanced chronic renal failure.
In 85 patients with established chronic renal failure, as manifested by serum creatinine concentration ([Cr]) > 0.177 mM (> 2 mg/dl), urinary clearance of 99mTc-DTPA (GFR) and [Cr] were determined one to four times and averaged. GFR was expressed per 3 m2 of height2 rather than in terms of 1.73 m2 of surface area because weight changes but height does not. GFR in these patients averaged 13 ml/min/3 m2 (range 2 to 37). The following equations were derived for predicting GFR from [Cr]-1 (mM-1), age (years) and weight (kg): males, GFR = 7.57 [Cr]-1 - 0.103 age + 0.096 weight - 6.66; females, GFR = 6.05 [Cr]-1 - 0.08 age + 0.08 weight - 4.81. These equations predict GFR in this series with a root mean square error of 3.0 ml/min and account for 89% of the observed variation in GFR. They are applicable only to patients with [Cr] > 0.177 mM (2 mg/dl). More precise estimates can be obtained by including a value for 24-hour urinary urea N, as a measure of protein intake. Less precise but simpler estimates can be obtained from [Cr]-1 alone: males, GFR = 7.58 [Cr]-1 - 4.29; females, GFR = 6.11 [Cr]-1 - 3.8. Expressing [Cr] in mg/dl, the latter equations become: males, GFR = 86 [Cr]-1 - 4.29; females, GFR = 69 [Cr]-1 - 3.8.


Hyaluronic acid combined with mannitol to improve protection against free-radical endothelial damage: experimental model.
To evaluate the protective properties of combined sodium hyaluronate 2% and mannitol 0.5% (Visiol) on the corneal endothelium in the presence of oxidative stress induced by hydrogen peroxide (H(2)O(2)). Instituto Oftalmológico de Alicante, Universidad Miguel Hernández, Alicante, Spain. This was an exploratory randomized controlled parallel-group, masked-assessor study of 3 sodium hyaluronate-based ophthalmic viscosurgical devices (OVDs): Visiol, Healon (sodium hyaluronate 1%), and Viscoat (sodium hyaluronate 3%-chondroitin sodium 4%). The OVDs were tested for protective effects on the endothelium following oxidative stress induced by H(2)O(2) at increased concentrations: control (lactated Ringer's solution), 1 mM, 10 mM, and 100 mM. Groups without OVD were used as controls at the same concentrations of peroxide. Each animal received the same treatment in both eyes (10 eyes per group). Endothelial cell lesion was assessed using the Janus green photometry absorbance technique. At 10 mM peroxide concentration, the value of endothelial cell lesion was significantly lower in the Visiol (16.8%, P=.0056), Healon (22.2%, P=.0302), and Viscoat (21.6%, P=.0336) groups than in the control group (29.4%, no OVD). There was a trend in favor of Visiol to more efficiently reduce cell lesions of the endothelium, than Healon (P=.055) and Viscoat (P=.1013). Values of endothelial cell lesion at peroxide concentrations of 1 mM and 100 mM showed the same trends than those observed at 10 mM. All of the OVDs tested efficiently reduced endothelial lesions against free radicals compared with the control group in which no OVD was used. The following sequence for the efficacy of endothelial cell protection was established: Visiol>Viscoat>Healon>no OVD.


Dentist perceptions about the value of teledentistry.
Teledentistry has expanded access to oral health care by allowing patients and providers the option to receive care using technology and telecommunications. This study used a cross-sectional, mixed-methods design to evaluate dentists' perceptions in the United States and understanding of the value and scope of teledentistry in their practices and to adopt virtual encounters as a care delivery methodology. This study used a cross-sectional, mixed-methods design. The DentaQuest Partnership for Oral Health Advancement (now CareQuest Institute for Oral Health) conducted an electronic survey of providers in the DentaQuest Network that assessed the impact of COVID-19 on dental practices' patient volume, staffing, dental insurance carriers, treatment protocols, and the office's pre-and post-COVID finances. A total of 2767 dental providers completed the survey with a response rate of 13%. Qualitative interviews were then conducted with ten providers to get more in-depth information on teledentistry. Descriptive statistics summarize the survey population. Thematic analysis, which allows both deductive and inductive approaches, were used to analyze the interviews. About 23% of the dentists used teledentistry or virtual platforms. Findings illustrate that early adopter dentists were more likely to perceive the benefits of teledentistry as being more significant than its drawbacks. Late/resistant adopters to teledentistry were less aware of its benefits and were more focused on the drawbacks, such as upfront cost. Late adopters were also concerned about the level of care delivered through teledentistry. This study explored dentists' perceptions of teledentistry. Expanding access to care was recognized as one of the greater values of teledentistry.


Exploring the prospective efficacy of waste bag-body contact allowance to reduce biomechanical exposure in municipal waste collection.
Municipal waste collectors must avoid bag-body contact, requiring waste bags to be held further from the body. Donning sharps-proof clothing would permit bag-body contact, allowing the bag to be closer to the body, reducing biomechanical exposures. To test this hypothesis, 25 participants loaded waste bags into a simulated garbage truck hopper under two lifting (contact allowed, no contact) and bag mass (7 kg and 20 kg) conditions. Bottom-up rigid-link biomechanical modelling results including peak low back compression force, antero-posterior shear force and peak low back flexion angle were not different between the lifting conditions, but cumulative compression was decreased with bag-body contact, although only at the 20 kg mass. Bag mass had significant effects on outcome measures, causing compression to increase to 4663 (±697) N, exceeding recommended thresholds. Sharps-proof clothing and municipally mandated 23 kg maximum allowable bag mass restrictions may not sufficiently reduce biomechanical exposures to prevent MSD.


Sumatriptan/Naproxen Sodium: A Review in Migraine.
Sumatriptan/naproxen sodium (Treximet®) is a fixed-dose combination of a serotonin 5-HT1B/1D receptor agonist (sumatriptan) and an NSAID (naproxen sodium), approved in the USA for the acute treatment of migraine with or without aura in adolescents and adults. In a randomized, phase 3 trial in adolescents, significantly more sumatriptan/naproxen sodium than placebo recipients were pain-free at 2 h. Similarly, in a pair of randomized phase 3 trials in adults, significantly more sumatriptan/naproxen sodium than placebo recipients had relief from migraine symptoms at 2 h, and the combination was more effective than individual components in terms of sustained (2-24 h) pain-free response rate. Sumatriptan/naproxen sodium was generally well tolerated, with ≤11 % of adolescents and ≤22 % of adults reporting treatment-related adverse events in the key clinical trials. The most common adverse reactions were nasopharyngitis, hot flushes and muscle tightness in adolescents, and dizziness, pain or pressure sensations, nausea, somnolence, dry mouth, dyspepsia and paraesthesia in adults. Based on current data, sumatriptan/naproxen sodium is a useful option for the acute treatment of migraine in adolescents and adults. The fixed-dose combination may reduce pill burden and improve adherence in some patients.


Optineurin in ocular herpes infection.
Herpes Simplex Virus-1 (HSV-1) is a neurotropic virus that can infect humans in the eye and travel to the trigeminal ganglion to establish latency. HSV-1 causes various disease states in both the primary and secondary sites of infection including the eye and the nervous system. This DNA virus exploits various adaptive measures to infect host cells, hijack host cell proteins, evade host immune response and spread from cell-to-cell to avoid immune detection. Recent data suggest that Optineurin (OPTN), a host protein, is a key restriction factor that prevents cell-to-cell spread of HSV-1 and guards against serious damage to the nervous system during infection. In recent years OPTN has gained increased attention because of its involvement in cellular mechanisms that promote homeostasis and prevent neurodegeneration. At the center of it all is the role OPTN plays as a receptor for selective autophagy. This review summarizes our latest understanding of the viral lifecycle, disease pathologies, and OPTN-mediated protective mechanisms during HSV-1 infection of the eye and the nervous system. We specifically highlight recent discoveries that implicate OPTN as crucial in the prevention of ocular and neurodegenerative diseases.


Violent attacks on public figures by persons suffering from psychiatric disorders. Their effect on the social distance towards the mentally ill.
In connection with two attempts on the lives of prominent politicians committed by mentally ill individuals during 1990 there occurred a marked increase in social distance towards the mentally ill among the German public. Even though the level of social distance subsided again during the 2 years following the attacks, it had not yet completely returned to its initial level by the end of 1992. The negative effects of these incidents on the attitude of the general public were able to be replicated on a regional level, after yet another violent attack by a mentally ill assailant in 1993, this time on the life of a famous female athlete.


WNT10B enhances proliferation through β-catenin and RAC1 GTPase in human corneal endothelial cells.
The cornea is the anterior, transparent tissue of the human eye that serves as its main refractive element. Corneal endothelial cells are arranged as a monolayer on the posterior surface of the cornea and function as a pump to counteract the leakiness of its basement membrane. Maintaining the cornea in a slightly dehydrated state is critical for the maintenance of corneal transparency. Adult human corneal endothelial cells are G1-arrested, even in response to injury, leading to an age-dependent decline in endothelial cell density. Corneal edema and subsequent vision loss ensues when endothelial cell density decreases below a critical threshold. Vision loss secondary to corneal endothelial dysfunction is a common indication for transplantation in developed nations. An impending increase in demand for and a current global shortage of donor corneas will necessitate the development of treatments for vision loss because of endothelial dysfunction that do not rely on donor corneas. Wnt ligands regulate many critical cellular functions, such as proliferation, making them attractive candidates for modulation in corneal endothelial dysfunction. We show that WNT10B causes nuclear transport and binding of RAC1 and β-catenin in human corneal endothelial cells, leading to the activation of Cyclin D1 expression and proliferation. Our findings indicate that WNT10B promotes proliferation in human corneal endothelial cells by simultaneously utilizing both β-catenin-dependent and -independent pathways and suggest that its modulation could be used to treat vision loss secondary to corneal endothelial dysfunction.


How could nanobiotechnology improve treatment outcomes of anti-TNF-α therapy in inflammatory bowel disease? Current knowledge, future directions.
Despite significant advances in therapeutic possibilities for the treatment of inflammatory bowel disease (IBD) in recent years, there is still a big room for improvement. In particular, biological treatment can induce not only clinical remission but also mucosal healing of the gastrointestinal tract. Among these therapeutic molecules, anti-tumor necrosis factor-alpha (anti-TNF-α) antibodies were the first to revolutionize treatment algorithms in IBD. However, due to the parenteral route of administration and systemic mode of action, TNF-α blockers are characterised by high rates of immunogenicity-related loss of response and serious adverse events. Moreover, intravenous or subcutaneous therapy is not considered patient-friendly and requires occasional, direct contact with healthcare centres. To overcome these limitations, several attempts have been made to design oral pharmaceutical formulations of these molecules. It is hypothesized that oral anti-TNF-α antibodies therapy can directly provide a targeted and potent anti-inflammatory effect in the inflamed gastrointestinal tissues without significant systemic exposure, improving long-term treatment outcomes and safety. In this review, we discuss the current knowledge and future perspectives regarding different approaches made towards entering a new era of oral anti-TNF-α therapy, namely, the tailoring of biocompatible nanoparticles with anti-TNF-α antibodies for site-specific targeting to IBD. In particular, we discuss the latest concepts applying the achievements of nanotechnology-based drug design in this area.


Methylene blue dosing strategies in critically ill adults with shock-A retrospective cohort study.
Shock increases mortality in the critically ill and the mainstay of therapy is the administration of vasopressor agents to achieve hemodynamic targets. In the past, studies have found that the NO-pathway antagonist methylene blue improves hemodynamics. However, the optimal dosing strategy remains elusive. Therefore, we investigated the hemodynamic and ICU outcome parameters of three different dosing strategies for methylene blue. We performed a retrospective cohort study of patients in shock treated with methylene blue. Shock was defined as norepinephrine dose >0.1 μg/kg/min and serum lactate level >2 mmol/l at the start of methylene blue administration. Different demographic variables, ICU treatment, and outcome parameters were evaluated. To compare the differences in the administration of vasopressors or inotropes, the vasoactive inotropic score (VIS) was calculated at different time points after starting the administration of methylene blue. Response to methylene blue or mortality at 28 days were assessed. 262 patients from July 2014 to October 2019 received methylene blue. 209 patients met the inclusion criteria. Three different dosing strategies were identified: bolus injection followed by continuous infusion (n = 111), bolus injection only (no continuous infusion; n = 59) or continuous infusion only (no bolus prior; n = 39). The groups did not differ in demographics, ICU scoring system, or comorbidities. In all groups, VIS decreased over time, indicating improved hemodynamics. Cardiogenic shock and higher doses of norepinephrine increased the chance of responding to methylene blue, while bolus only decreased the chance of responding to methylene blue treatment. 28-day mortality increased with higher SAPSII scores and higher serum lactate levels, while bolus injection followed by continuous infusion decreased 28-day mortality. No severe side effects were noted. In this cohort, methylene blue as a bolus injection followed by continuous infusion was associated with a reduced 28-day mortality in patients with shock. Prospective studies are needed to systematically evaluate the role of methylene blue in the treatment of shock.


Idiopathic granulomatous hypophysitis presenting with galactorrhea, headache, and nausea in a woman: a case report and review of the literature.
Inflammation of the pituitary gland can occur in a variety of primary or secondary disorders. Idiopathic granulomatous hypophysitis is a rare inflammatory disease of the pituitary gland that can closely mimic a pituitary adenoma clinicoradiologically. Most authorities agree on minimally invasive transsphenoidal surgery as the mainstay in diagnosis and treatment of this disorder. There is still some controversy regarding pure medical management of idiopathic granulomatous hypophysitis in the literature. A 47-year-old Iranian woman of Azeri ethnicity with a history of benign breast cysts with a chief complaint of galactorrhea presented to our endocrinology clinic. Her past medical history was negative for any menstrual irregularities, hirsutism, visual complaints, diplopia, polyuria and polydipsia or seizures. She was taking 100 mcg of levothyroxine daily. Her familial history and physical examination were unremarkable. Her initial laboratory work-up revealed hyperprolactinemia (82.4 ng/mL) with otherwise normal pituitary axes. Brain magnetic resonance imaging showed a pituitary macroadenoma for which she was treated with 0.5 mg of cabergoline weekly. Although her serum prolactin level dropped to 1.7 ng/mL and her galactorrhea was resolved, she continued to complain of headaches and nausea. Repeated imaging showed no decrease in size of the macroadenoma. Therefore, she underwent transsphenoidal surgery of the macroadenoma which was reported as chronic granulomatous hypophysitis by expert pathologists. Tuberculosis, sarcoidosis, Wegener's granulomatosis, Langerhans cell histiocytosis, and syphilis were ruled out by appropriate tests and she was diagnosed as having idiopathic granulomatous hypophysitis. Fortunately, her condition was not complicated by hypopituitarism and she was symptom free 9 months after transsphenoidal surgery. Idiopathic granulomatous hypophysitis, a rare inflammatory disease of the pituitary gland, is a diagnosis of exclusion for which both medical and surgical management are reported in the literature. We present a case of idiopathic granulomatous hypophysitis who was symptom free with no complications of hypopituitarism following its transsphenoidal resection after 9 months of follow-up.


Seeding experiments demonstrate poor performance of the hatching test for detecting small numbers of Schistosoma mansoni eggs in feces.
Parasitological methods for the evaluation of schistosomiasis tend to be limited when parasitic burdens are low, which is a major characteristic of low intensity transmission areas. While the hatching test (HT) method has been considered to be "very sensitive", reports of its capacity to detect low numbers of eggs remain scarce in the published literature. Our main hypothesis is that HT has limitations and cannot be recommended for diagnosing light infections or as a control of cure. Hence, this study aims to describe the performance of HT in detail, with respect to seeding experiments for egg numbers in the range of 4 to 24 eggs per gram (epg) of feces. Different numbers of eggs of Schistosoma mansoni were seeded in normal human feces. The first set of experiments evaluated the amount of feces (higher than 0.5 g prevented hatching), the proximity of the light source (50 cm was preferred), and the observation time required for the detection of miracidia (more than 3h did not add to sensitivity). HT was subsequently performed with 12, 10, 8, 6, 4, and 2 eggs in 0.5 g of feces. The final set of experiments was performed to analyze the initial filtration step, in which surgical gauze versus a 500 μm nylon mesh was compared and demonstrated losses of eggs that occurred with washing and gauze (better with nylon) sieving steps. The proposed method was found to produce 100% positivity for up to 12 epg, with a sharp decrease to 33% for 8 epg and less. In conclusion, HT is not recommended for diagnosing intestinal schistosomiasis in populations with light infections, considering the complexity of the procedure and its lack of effectiveness with fecal amounts higher than 0.5 g even at optimized conditions.


The identification and characteristics of salinity-related microRNAs in gills of Portunus trituberculatus.
MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate gene expression in organisms. To understand the underlying mechanisms behind the molecular response of the crab to low salt-stress, high-throughput Illumina/Solexa deep sequencing technology was used to investigate the expression profiles of miRNAs under low salinity challenged. Two mixed RNA pool libraries of gill tissues from low salinity challenged (LC) and the control groups (NC) were sequenced on the Illumina platform. A total of 6,166,057 and 7,032,973 high-quality reads were obtained from the NC and LC libraries, respectively. Sixty-seven miRNAs consisting of 16 known and 51 novel ones were identified, among which, 12 miRNAs were differentially expressed in LC compared to NC. Thirty-four of the target genes predicted were differentially expressed in the opposite direction to the miRNAs, which were involved in crucial processes related to osmoregulation by gene ontology (GO) functional enrichment analysis, such as anion transport processes (GO:0006820) and chitin metabolic process (GO:0006030). These results provide a basis for further investigation of the miRNA-modulating networks in osmoregulation of Portunus trituberculatus.


Mutations in the dimer interfaces of the dengue virus capsid protein affect structural stability and impair RNA-capsid interaction.
The dengue virus 2 capsid protein (DENV2C) plays a primary structural role in the protection of the viral genome and is crucial for nucleocapsid assembly. In this study, we generated single mutants of DENV2C at L50 and L54 residues of the α2 helix, which was shown to interfere with the integration of the capsid into lipid droplets, and at residues L81 and I88 located in the α4 helix, which was shown to affect viral assembly. We demonstrated that the oligomeric states of DENV2C and its mutants exist primarily in the dimeric state in solution. All single-point mutations introduced in DENV2C promoted reduction in protein stability, an effect that was more pronounced for the L81N and I88N mutants, but not protein unfolding. All the single-point mutations affected the ability of DEN2C to interact with RNA. We concluded that mutations in the α2-α2' and α4-α4' dimer interfaces of DENV2C affect the structural stability of the protein and impair RNA-capsid interaction. These effects were more pronounced for mutations at the L81 and I88 residues in the α4 helix. These results indicate the importance of the α4-α4' dimer interface, which could be studied as a potential target for drug design in the future.


Oscillatory interlayer exchange coupling and its temperature dependence in [Pt/Co]3/NiO/[Co/Pt]3 multilayers with perpendicular anisotropy.
Interlayer exchange coupling that oscillates between antiferromagnetic and ferromagnetic as a function of NiO thickness has been observed in [Pt(5 A)/Co(4 A)](3)/NiO(t(NiO) A)/[Co(4 A)/Pt(5 A)](3) multilayers with out-of-plane anisotropy. The period of oscillation corresponds to approximately 2 monolayers of NiO. This oscillatory behavior is possibly attributed to the antiferromagnetic ordering in NiO. The antiferromagnetic interlayer exchange coupling for the 11 A NiO layer shows an increase in coupling strength with increasing temperature, in agreement with the quantum interference model of Bruno for insulating spacer layers. A coexistence of exchange biasing and antiferromagnetic interlayer exchange coupling has been observed below T=250 K.


137Cs distribution on the territory of Romania 30 years after Chernobyl accident.
To estimate the contribution of Chernobyl 137Cs contamination, in 1993 and especially 2016, its total inventory was determined by gamma-ray high-resolution spectroscopy in 62 and respectively 747 soil samples covering the entire Romanian territory. This permitted to estimate the 137Cs inventory as varying between 0.4 and 187 as well as between 0.2 and 94.2 kBq/m2 for years 1993 and 2016, respectively. By representing the spatial distribution of 137Cs inventory in Voronoi polygons, it was possible to evidence a decrease of the total 137Cs inventory over entire Romanian territory with a factor of about 3 from about 3.6 TBq to less than 1.2 TBq, exceeding in this way the natural decay which suggests that a certain amount of 137Cs was washed out by precipitation and, at a lower extent, was incorporated into plants. At the same time, by evaluating the maximum contribution of 137Cs to the population exposure, in 1993 as well as in 2016, the supplementary annual effective dose did not exceed, in the majority of sampling points the value of 0.2 mSv/year.


Perceived path of oblique motion: horizontal-vertical and stimulus-orientation effects.
Subjects adjusted the path of moving stimuli to produce apparent slopes of 45 degrees with respect to horizontal. The stimulus was either a single moving dot or a vertical or horizontal bar. In separate experiments either the stimuli were tracked or fixation was maintained on a stationary fixation target positioned 8 deg to the right of the center of stimulus motion. In both experiments the selected path slopes were in general more horizontal than 45 degrees. This pattern indicates that subjects overestimate the vertical component of motion along an oblique path, and is interpreted as a manifestation of the spatial anisometropy generally termed the 'horizontal-vertical illusion'. Additionally, paths selected for horizontal bars were more vertical than those for vertical bars. This finding is interpreted in the context of a previous report of the influence of stimulus orientation on perceived velocity.


Oleanolic Acid Exerts a Neuroprotective Effect Against Microglial Cell Activation by Modulating Cytokine Release and Antioxidant Defense Systems.
Microglia respond to adverse stimuli in order to restore brain homeostasis and, upon activation, they release a number of inflammatory mediators. Chronic microglial overactivation is related to neuroinflammation in Alzheimer's disease. In this work, we show that oleanolic acid (OA), a natural triterpene present in food and medicinal plants, attenuates the activation of BV2 microglial cells induced by lipopolysaccharide (LPS). Cell pretreatment with OA inhibited the release of IL-1β, IL-6, TNF-α, and NO, which was associated with the downregulation of the expression of genes encoding for these cytokines and inducible nitric oxide synthase (iNOS), and the reinforcement of the endogenous antioxidant cell defense. These findings advocate considering OA as a novel neuroprotective agent to inhibit oxidative stress and inflammatory response in activated microglia associated with Alzheimer's disease.


Trapping radioactive carbon dioxide during cellular metabolic assays under standard culture conditions: description of a unique gas-capturing device.
Measurement of carbon dioxide levels has been employed to follow cellular metabolic reactions for quite some time. By radio-labeling substrate molecules and evaluating the radioactivity levels of the carbon dioxide released, insight into metabolic pathways can be gleaned. Currently, no carbon dioxide capturing device is available that can be used with large volume cell monolayers growing under standard conditions within a regular commercially available culture flask. In this note we describe a simple device for collecting radio-labeled carbon dioxide from a standard culture flask. The device is independent of the culture flask, but can be attached for metabolic measurements allowing cells to be grown under standard conditions prior to study. The presented design permits convenient transfer of the device between flasks without contaminating or disturbing cells growing within the flasks. Data are presented demonstrating the reproducibility of measurements made with multiple devices with different substrate concentrations and varying periods of time, ranging up to 3 h.


The rate and degree of food compensation on alteration of its caloric density in rats.
The ability to regulate energy level by male albino rats on administration of food with varying caloric densities, was studied. The animals fed different caloric density diets exhibited marked variations in their caloric in take in the initial stages which stabilized after 5 to 10 days and maintained on lower mean caloric intake on diet having density of 2.63 Kcal/gm, and higher mean caloric intake on diet with density of 4.88 Kcal/gm. Similar variations in body weight were also evident with failure to maintain the body weight with caloric dilution.


The role of extracellular potassium transport in computer models of the ischemic zone.
Ischemic heart disease is associated with large mortality and morbidity. Understanding of the relations between coronary artery occlusion, geometry of the ischemic region, physiology of ischemia, and the resulting changes in electrocardiogram (ECG) leads and catheter signals is important to support diagnosis and treatment. Computer models play an important role in understanding ischemia, by linking experimental to clinical results. In this paper we argue that the observed transport of extracellular potassium should be represented in such models. We used a diffusion equation to describe the transport mechanism. This model reproduced the measured spatial distribution of potassium, and its temporal development. We discuss the role of potassium transport next to other aspects of ischemia: the mechanism of changes in action potential and ECG, cellular coupling, anisotropic bidomain tissue conductivity, and the geometry of the ischemic zone.


[Preliminary data on the behavior of the enzyme of metabolism of phospholipid bases in human tumor preparations].
The A.A. have investigated the phospholipids base-exchange enzyme system in the solid tumours in order to state if a correlation between this activity and the variation of the cellular ciclic nucleotides amount was possible considering that these compounds have been reported to undergo a variation in tumour compared with normal tissues. They report some previous results in a lung tumour and in an endometrial carcinoma, were they have found a big increase in the PhS synthesis. Such increase was possible to be seen in the endometrial carcinoma only after a stimulation by 17-beta-estradiol and it was reversed in this case by doxorubicine. These results suggest that an alteration of the PhS synthesis should be one of numerous peculiarity of the neoplastic cell.


Clinically non-functioning pituitary adenomas.
Clinically non functioning pituitary adenomas (NFPAs) include all pituitary adenomas that are not hormonally active. They are not associated with clinical syndromes such as amenorrhea-galactorrhea (prolactinomas), acromegaly, Cushing's disease or hyperthyroidism (TSH-secreting adenomas) and are therefore usually diagnosed by signs and symptoms related to a mass effect (headache, visual impairment, sometimes pituitary apoplexy), but also incidentally. Biochemical work up often documents several pituitary insufficiencies. In histopathology, the majority of NFPAs are gonadotroph. In the absence of an established medical therapy, surgery is the mainstay of treatment, unless contraindicated or in particular situations (e.g. small incidentalomas, distance from optic pathways). Resection, generally via a trans-sphenoidal approach (with the help of an endoscope), should be performed by a neurosurgeon with extensive experience in pituitary surgery, in order to maximize the chances of complete resection and to minimize complications. If a tumor remnant persists, watchful waiting is preferred to routine radiotherapy, as long as the tumor residue does not grow and is distant from the optic pathways. NFPA can sometimes recur even after complete resection, but predicting the individual risk of tumor remnant progression is difficult. Postoperative irradiation is only considered in case of residual tumor growth or relapse, due to its potential side effects.


Rhythmic exercises in rehabilitation of TBI patients: a case report.
Patients who have sustained traumatic brain injury (TBI) often present with a multiplicity of dysfunctions making rehabilitation challenging. Patients who have taken part in studies of rehabilitation exercises that incorporated monotonous timed auditory cues (using a metronome) following cerebrovascular events demonstrated improvement in gait and motor functions. The purpose of this case report is to describe the efficacy of Rhythmic Exercises with Auditory Cues (REAC) to improve functions in a patient, years after their traumatic brain injury. A single case report of a 24-year-old female patient, nine years post hemispherectomy following TBI that resulted in right hemiparesis. The patient was taught to perform REAC exercises at home. These exercises were designed to activate the body while Alternating hands and feet Bilaterally with Cross-midline movements for a short Duration while synchronizing the movements with a metronome as a Rhythm regulator. Outcome measurements included gait and functional assessment and cognitive and psychological instrument scores that were compared pre and post treatment. Clinical improvement was observed in the patient's gait pattern with reduced hip hiking motion and increased cadence. There was a decrease in spasticity in the right arm and leg with some isolated volitional movements of the hand and fingers returning. She also regained sensation in her right arm and leg. Cognitive improvement was demonstrated by increased IQ scores from 78 to 94.


Preparation of nanofibrillated cellulose from grapefruit peel and its application as fat substitute in ice cream.
Grapefruit peel nanofibrillated cellulose (GNFC) was used as fat substitute in ice cream. GNFC was characterized by TEM, SEM, and XRD. The effects of GNFC on textural profiles, rheological properties, melting resistance, sensory properties, microstructure, and gross energy (GE) of ice cream were investigated. The results showed that GNFC was short rod-shaped crystal. Ice cream added with GNFC exhibited elastic-dominated behavior and better textural properties. The sensory evaluation score reached the highest level with desirable three-dimensional network structure at 0.4 % GNFC addition. GE of ice cream significantly decreased with reducing fat with maximal reduction rate of 17.90 %. Furthermore, the results of in vitro simulated digestion showed that GNFC addition and fat reduction significantly inhibited fat digestibility of ice cream due to coalescence of fat droplets on GNFC. This study provides new sustainable perspectives for the application of GNFC prepared from agricultural waste as fat substitute in food products.


Neural correlates of the relationship between discourse coherence and sensory monitoring in schizophrenia.
Unusual language use is a core feature of psychosis, but the nature and significance of this are not understood. In particular, thought disorder in schizophrenia (SZ) is characterized by markedly bizarre speech, but the cognitive components that contribute to this and the brain correlates of these components are unknown. A number of studies have demonstrated language abnormalities in single word processing, but few have examined speech in SZ at the discourse level. This has been at least partly due to the difficulty in quantifying content of discourse. Recently, methods in computational linguistics have been found to be useful for detecting differences in semantic coherence during discourse between different clinical groups. We build on this work by demonstrating how these methods can be combined with funtional magnetic resonance imaging (fMRI) in order to tease apart factors that underlie free discourse and its deviations, and how they relate to brain activity. Eleven volunteers with SZ and eleven controls participated in an interview during which they were asked to talk as much as they could about 'religious belief'. These same participants underwent fMRI during a word monitoring task, during which modality of monitoring was manipulated by varying the congruence of auditory and visual stimuli. Semantic coherence scores, measured from free discourse, were examined for their relationship to brain activations during fMRI. In healthy controls, regions associated with executive function were related to coherence. In persons with SZ, coherence was mainly related to auditory and visual regions, depending on the modality of monitoring, but superior/middle temporal cortex related to coherence regardless of task. These findings are consistent with existing evidence for a role of superior temporal cortex in thought disorder, and demonstrate that computational measures of semantic content capture objective measures of coherence in speech that can be usefully related to underlying neurophysiological processes.


Diphtheria-tetanus-acellular pertussis vaccine adsorbed (Triacelluvax; DTaP3-CB): a review of its use in the prevention of Bordetella pertussis infection.
DTaP3-CB (Triacelluvax) is an acellular pertussis (aP) vaccine containing 3 antigens from purified Bordetella pertussis bacteria combined with diphtheria and tetanus toxoids (DT). In addition to purified filamentous haemagglutinin and pertactin, DTaP3-CB contains pertussis toxin which has been genetically rather than chemically detoxified. As shown in randomised, double-blind clinical trials in infants, DTaP3-CB elicits an immune response similar to or greater than that of whole cell (DTwP) vaccines. Results of a large multicentre study comparing DTaP3-CB with 12 acellular and 1 DTwP vaccine indicate that DTaP3-CB, like all acellular vaccines, induces variable immune responses to different pertussis antigens; however, antibody titres to pertussis toxin are normally higher after immunisation with the genetically detoxified vaccine than with other 3- or 4-component vaccines. When given as a fourth or fifth booster dose, DTaP3-CB produced a significant immune response in infants primed with 3 doses of either a DTaP or DTwP vaccine. Virtually all infants immunised with DTaP3-CB had a serological response to diphtheria and tetanus toxoids. Data from 2 very large efficacy studies indicate that DTaP3-CB has high and long lasting protective efficacy against culture-confirmed pertussis which is greater than that of a 2-component vaccine (DTaP2-SB) and the whole cell DTwP-CON vaccine after a 3-, 5- and 12-month immunisation schedule and after a 2-, 4- and 6-month schedule with the DTwP-CON vaccine. However, the DTwP-CON whole cell vaccine has been noted for its low immunogenicity in 1 study and low efficacy and immunogenicity in another study. On the other hand, DTaP3-CB vaccine has similar efficacy to DTaP3-SB (after immunisation at 2, 4 and 6 months), DTaP5-CON and DTwP-EVANS against culture-confirmed pertussis with > or =21 days cough in infants immunised according to a 3-, 5- and 12-month schedule. Infants immunised with DTaP3-CB experienced significantly fewer adverse events such as pain, redness, swelling and irritability than infants given DTwP. DTaP3-CB has a similar tolerability profile to other acellular vaccines and is associated with similar rates of local tenderness, irritability, fever (> or =40 degrees C) and persistent crying. Comparative trials have shown that infants immunised with DTaP3-CB had a lower incidence of pain at the site of injection and fever (> or =38 degrees C) compared with other acellular vaccines, although this may have little clinical significance. Concomitant administration of DTaP3-CB with hepatitis B, oral polio or Haemophilus influenzae type B vaccines did not affect the immunogenicity of these other paediatric vaccines. Data from clinical trials with DTaP3-CB vaccine indicate that this vaccine induces high and long lasting efficacy. It is at least as efficacious as most whole cell vaccines and generally similar in efficacy to the most efficacious acellular pertussis vaccines containing 3 or more pertussis antigens. DTaP3-CB is better tolerated than whole cell vaccines and has a similar tolerability profile to other acellular vaccines; the possible lower risk of severe adverse events remains to be confirmed. The low reactogenicity of DTaP3-CB is likely to make it well tolerated and therefore well accepted for the immunisation of infants, thereby enabling wider implementation of vaccination programmes.


Clonal chromosome rearrangements in a fibroblast strain from a patient affected by xeroderma pigmentosum (complementation group C).
We report the results of DNA repair studies and cytogenetic investigations in a patient presenting acute phothosensitivity and cancerous skin lesions. In lymphocytes and fibroblasts a reduced level of unscheduled DNA synthesis after UV irradiation was found and the presence of xeroderma pigmentosum, complementation group C, mutation was demonstrated by complementation analysis. In lymphocyte and fibroblast cultures the frequency of spontaneous chromosome gaps and breaks was normal, whereas the frequency of chromosome rearrangements was higher than expected. In fibroblasts from the 4th to the 18th passage of the culture, 4 reciprocal translocations with a clonal distribution were identified. The rearranged chromosomes were Nos. 2, 13, 14 and 15, Nos. 2 and 13 being both involved in 3 different translocations with breakpoints at 2q21, 2q31, 2p23 and 13q31, 13q12 or 3. The biological significance of this finding is discussed in view of a possible correlation with the DNA repair defect and a possible relevance in tumor development of specific chromosome rearrangements.


Neuropeptide Y: regional distribution chromatographic characterization and immunohistochemical demonstration in post-mortem human brain.
Using a neuropeptide Y (NPY)-directed radioimmunoassay the post-mortem stability of NPY was assessed in both rat and human brain samples. The regional distribution of NPY-like immunoreactivity in human brain was determined. The NPY-like immunoreactivity in human brain separated on Sephadex G-50 columns and 18C reverse phase at the position expected for NPY. Immunohistochemical staining using the NPY-directed antiserum revealed a characteristic population of cortical and striatal neurons containing NPY-like immunoreactivity.


The role of zinc in caspase activation and apoptotic cell death.
In addition to its diverse role in many physiological systems, zinc (Zn) has now been shown to be an important regulator of apoptosis. The purpose of this review is to integrate previously published knowledge on Zn and apoptosis with current attempts to elucidate the mechanisms of action of this biometal. This paper begins with an introduction to apoptosis and then briefly reviews the evidence relating Zn to apoptosis. The major focus of this review is the mechanistic actions of Zn and its candidate intracellular targets. In particular, we examine the cytoprotective functions of Zn which suppress major pathways leading to apoptosis, as well as the more direct influence of Zn on the apoptotic regulators, especially the caspase family of enzymes. These two mechanisms are closely related since a decline in intracellular Zn below a critical threshold level may not only trigger pathways leading to caspase activation but may also facilitate the process by which the caspases are activated. Studies by our laboratory in airway epithelial cells show that Zn is co-localized with the precursor form of caspase-3, mitochondria and microtubules, suggesting this Zn is critically placed to control apoptosis. Further understanding the different pools of Zn and how they interact with apoptotic pathways should have importance in human disease.


Model of THz Magnetization Dynamics.
Magnetization dynamics can be coherently controlled by THz laser excitation, which can be applied in ultrafast magnetization control and switching. Here, transient magnetization dynamics are calculated for excitation with THz magnetic field pulses. We use the ansatz of Smit and Beljers, to formulate dynamic properties of the magnetization via partial derivatives of the samples free energy density, and extend it to solve the Landau-Lifshitz-equation to obtain the THz transients of the magnetization. The model is used to determine the magnetization response to ultrafast multi- and single-cycle THz pulses. Control of the magnetization trajectory by utilizing the THz pulse shape and polarization is demonstrated.


Endothelial cell loss after phacoemulsification and insertion of silicone lens implants.
Central corneal endothelial cell loss was compared following primary insertion of folded posterior chamber silicone intraocular lenses (IOLs) in 29 eyes and Sinskey-style polymethylmethacrylate posterior chamber IOLs in 20 eyes. Cataracts were removed by phacoemulsification and sodium hyaluronate was used in all cases. The mean follow-up time was greater than seven months. The average cell loss was 9.6% and 10.9%, respectively. There was no significant difference in cell loss or visual results in the two groups. The amount of cell loss compares favorably with other series in which cell loss was determined following cataract surgery with and without IOL implantation.


Repositioning the existing drugs for neuroinflammation: a fusion of computational approach and biological validation to counter the Parkinson's disease progression.
Parkinson's disease is caused by the deficiency of striatal dopamine and the accumulation of aggregated α-synuclein in the substantia nigra pars compacta (SNpc). Neuroinflammation associated with oxidative stress is a key factor contributing to the death of dopaminergic neurons in SNpc and advancement of Parkinson's disease. Two molecular targets, i.e., nuclear factor kappa-light-chain-enhancer (NF-kB) and α-synuclein play a substantial role in neuroinflammation progression. Therefore, the compounds targeting these neuroinflammatory targets hold a great potential to combat Parkinson's disease. Thereby, in this study, molecular docking and Connectivity Map (CMap) based gene expression profiling was utilized to reposition the approved drugs as neuroprotective agents for Parkinson's disease. With in silico screening, two drugs namely theophylline and propylthiouracil were selected for anti-neuroinflammatory activity evaluation in in vivo models of chronic neuroinflammation. The neuroinflammatory effect of the identified compounds was confirmed by quantifying the expression of three important neuroinflammatory mediators, i.e. IL-6, TNF-alpha, and IL-1 beta on brain tissue using ELISA assay. The ELISA experiment demonstrated that both compounds significantly decreased the expression of neuroinflammatory mediators, highlighting the compounds' potential in neuroinflammation management. Furthermore, the drug and disease interaction network of the two identified drugs and diseases (neuroinflammation and Parkinson's disease) suggested that the two drugs might interact with various targets namely adenosine receptors, Poly [ADP-ribose] polymerase-1, myeloperoxidase (MPO) and thyroid peroxidase through multiple pathways associated with neuroinflammation and Parkinson's disease. Computational studies suggest that a particular drug may be effective in managing Parkinson's disease associated with neuroinflammation. However, further research is needed to confirm this in biological experiments.


Subarachnoid hemorrhage in a postpartum mother: A rare manifestation of an uncommon disease.
Subarachnoid hemorrhage, a potentially lethal medical emergency, represents an atypical clinical manifestation of gestational choriocarcinoma. We present the uncommon case of a 31-year-old primigravid female who presented with cerebral oncotic aneurysmal rupture, five weeks after vaginal delivery. Albeit the absence of neurological deficits after endovascular embolization, the patient was soon readmitted, complaining of fever, abdominal pain, and fetid lochia, all suggestive of puerperal endometritis. Upon a comprehensive diagnostic work-up, she was subsequently diagnosed with metastatic choriocarcinoma. Early initiation of multiagent chemotherapy, despite being in septic shock associated with Escherichia coli bacteremia, resulted in favorable prognosis.


A compositional shift in the soil microbiome induced by tetracycline, sulfamonomethoxine and ciprofloxacin entering a plant-soil system.
Antibiotics entering the soil likely disturb the complex regulatory network of the soil microbiome, which is closely associated with soil quality and ecological function. This study investigated the effects of tetracycline (TC), sulfamonomethoxine (SMM), ciprofloxacin (CIP) and their combination (AM) on the bacterial community in a soil-microbe-plant system and identified the main bacterial responders. Antibiotic effects on the soil microbiome depended on antibiotic type and exposure time. TC resulted in an acute but more rapidly declining effect on soil microbiome while CIP and SMM led to a delayed antibiotic effect. The soil exposed to AM presented a highly similar bacterial structure to that exposed to TC rather than to SMM and CIP. TC, SMM and CIP had their own predominantly impacted taxonomic groups that include both resistance and sensitive bacteria. The antibiotic sensitive responders predominantly distributed within the phylum Proteobacteria. The potential bacteria resistant to each antibiotic exhibited phyla preference to some extent, particularly those resistant to TC. CIP and SMM resistance in soil was increased with exposure time while TC resistance gave the opposite result. Overall, the work extended the understanding of antibiotic effects on soil microbiome after introduced into the soil during greenhouse vegetable cultivation.


Indole alkoloids from Nauclea officinalis with weak antimalarial activity.
Five indole alkaloids (naucleofficines A-E) were isolated from the stems (with bark) of Nauclea officinalis: (E)-2-(1-beta-d-glucopyranosyloxybut-2-en-2-yl)-3-(hydroxymethyl)-6,7-dihydro-indolo[2,3-a]quinolizin-4(12H)-one (1), (E)-1-propenyl-12-beta-d-glucopyranosyloxy-2,7,8-trihydro-indolo[2,3-a]pyran[3,4-g]quinolizin-4,5(13H)-dione (2), (E)-2-(1-hydroxybut-2-en-2-yl)-11-beta-d-glucopyranosyloxy-6,7-dihydro-indolo[2,3-a]quinolizin-4(12H)-one (3), (E)-1-propenyl-4-hydroxy-2,4a,7,8,13b,14,14a-hepthydro-(4alpha,4abeta,13balpha,14abeta)indolo[2,3-a]pyran[3,4-g]quinolizin-5(13H)-one (4) and 1-(1-hydroxyethyl)-10-hydroxy-7,8-dihydro-indolo[2,3-a]pirydine[3,4-g]quinolizin-5(13H)-one (10-hydroxyangustoline) (5), together with two known compounds, naucleidinal (6) and angustoline (7). All of the structures of the seven compounds above were elucidated by spectroscopic methods including use of 1D- and 2D-NMR spectroscopic analyses. Compounds 2 and 3 are rare examples of monoterpene indole alkaloids with a glucopyranosyloxy group attached to position C-12. In vitro activity screening of the above seven compounds showed weak to moderate inhibitory activity against Plasmodium falciparum.


Complementary school garden, nutrition, water, sanitation and hygiene interventions to improve children's nutrition and health status in Burkina Faso and Nepal: a study protocol.
Malnutrition and intestinal parasitic infections are common among children in Burkina Faso and Nepal. However, specific health-related data in school-aged children in these two countries are scarce. In the frame of a larger multi-stakeholder project entitled "Vegetables go to School: Improving Nutrition through Agricultural Diversification" (VgtS), a study has been designed with the objectives to: (i) describe schoolchildren's health status in Burkina Faso and Nepal; and to (ii) provide an evidence-base for programme decisions on the relevance of complementary school garden, nutrition, water, sanitation and hygiene (WASH) interventions. The studies will be conducted in the Centre Ouest and the Plateau Central regions of Burkina Faso and the Dolakha and Ramechhap districts of Nepal. Data will be collected and combined at the level of schools, children and their households. A range of indicators will be used to examine nutritional status, intestinal parasitic infections and WASH conditions in 24 schools among 1144 children aged 8-14 years at baseline and a 1-year follow-up. The studies are designed as cluster randomised trials and the schools will be assigned to two core study arms: (i) the 'complementary school garden, nutrition and WASH intervention' arm; and the (ii) 'control' arm with no interventions. Children will be subjected to parasitological examinations using stool and urine samples and to quality-controlled anthropometric and haemoglobin measurements. Drinking water will be assessed for contamination with coliform bacteria and faecal streptococci. A questionnaire survey on nutritional and health knowledge, attitudes and practices (KAP) will be administered to children and their caregivers, also assessing socioeconomic, food-security and WASH conditions at household level. Focus group and key-informant interviews on children's nutrition and hygiene perceptions and behaviours will be conducted with their caregivers and school personnel. The studies will contribute to fill a data gap on school-aged children in Burkina Faso and Nepal. The data collected will also serve to inform the design of school-based interventions and will contribute to deepen the understanding of potential effects of these interventions to improve schoolchildren's health in resource-constrained settings. Key findings will be used to provide guidance for the implementation of health policies at the school level in Burkina Faso and Nepal. ISRCTN30840 (date assigned: 17 July 2015).


Bacteria causing false positive test for phosphatidylglycerol in amniotic fluid.
A case is reported in which phosphatidylglycerol was detected in a sample of vaginal pool amniotic fluid but absent in amniotic fluid obtained at amniocentesis. Bacteria contaminating the fluid are shown to be capable of phosphatidylglycerol production.


Dead bodies for the anatomical institute in the Third Reich: An investigation at the University of Jena.
During the period of 2004-2005, a group of anatomists and historians investigated the origin of dead bodies received by the anatomical institute of the University of Jena in the Third Reich. Between 1933 and 1945, the institute received the bodies of 203 executed persons, most of whom had been sentenced to death for relatively minor offenses or opposition to National Socialist (NS) regulations. Moreover, the institute received about 200 bodies of possible "euthanasia" victims from nearby nursing homes and mental institutions, and several dozen dead bodies of forced laborers from Eastern Europe. Many of these persons must be considered victims of NS injustice. One of the central questions of the investigation was whether any remains of NS victims were still present in the anatomical collections of the institute. At their own initiative, members of the anatomical institute initiated the investigation after a change of leadership at the institute. The investigation was characterized by (1) a scholarly approach thanks to the participation of expert historians, (2) transparency, including early and full information of the press, (3) documentation and publication of the results at the national and international level, (4) appropriate consequences for the anatomical collections, and (5) commemoration of the victims. This and other recent investigations demonstrate that a new generation of German anatomists has begun to uncover the role of their institutes during the Third Reich, finally overcoming the phase of silence in postwar German anatomy.


Rise in intraocular pressure with elevator travel in post-vitrectomy patients.
To evaluate the impact of elevator travel on intraocular pressure after vitreoretinal surgery with gas tamponade. Patients undergoing pars plana vitreoretinal surgery with and without gas insertion were recruited on post-operative day 1. All intraocular pressures were measured three times by Tono-Pen AVIA (Reichert, USA) on the fourth floor and, after rapid ascent in an elevator, on the 12th floor of the hospital. All patients were observed and asked for any symptoms of pain or nausea for at least 15 min. In this study, 54 patients were recruited. Twenty-seven patients underwent vitreoretinal procedures with gas insertion, while 27 patients without gas insertion acted as controls. The mean age of patients was 60.9 years. The mean changes in intraocular pressure of the patients with gas insertion (+ 1.39 mmHg) were greater than those without gas insertion (- 0.43 mmHg) and statistically significantly different (95% CI 1.17-2.48, P < 0.0001). Patients undergoing vitreoretinal surgery with gas insertion had statistically significant intraocular pressure rise even with 8-floor ascent in the immediate post-operative period. Further studies are needed to evaluate the change in intraocular pressure with a larger range of altitudes and different gases.


Transformation of diploid human fibroblasts by transfection with the v-sis, PDGF2/c-sis, or T24 H-ras genes.
Gene transfection techniques have provided powerful methods to examine the roles of cellular and retroviral oncogenes in the transformation process in rodent fibroblasts. However, the use of such techniques with diploid human fibroblasts has been limited. We have developed transfection procedures to reproducibly transfect such cells with oncogenes, and methods for the biological characterization of the transformants. We have shown that the v-sis and T24 H-ras oncogenes, as well as the platelet-derived growth factor gene (PDGF2/c-sis), are capable of inducing a transformed phenotype in normal diploid human fibroblasts, but are not capable of conferring infinite lifespan or making such cells tumorigenic.


The equilibrium of tumor suppression: DUBs as active regulators of PTEN.
PTEN is among the most commonly lost or mutated tumor suppressor genes in human cancer. PTEN, a bona fide lipid phosphatase that antagonizes the highly oncogenic PI3K-AKT-mTOR pathway, is considered a major dose-dependent tumor suppressor. Although PTEN function can be compromised by genetic mutations in inherited syndromes and cancers, posttranslational modifications of PTEN may also play key roles in the dynamic regulation of its function. Notably, deregulated ubiquitination and deubiquitination lead to detrimental impacts on PTEN levels and subcellular partitioning, promoting tumorigenesis. While PTEN can be targeted by HECT-type E3 ubiquitin ligases for nuclear import and proteasomal degradation, studies have shown that several deubiquitinating enzymes, including HAUSP/USP7, USP10, USP11, USP13, OTUD3 and Ataxin-3, can remove ubiquitin from ubiquitinated PTEN in cancer-specific contexts and thus reverse ubiquitination-mediated PTEN regulation. Researchers continue to reveal the precise molecular mechanisms by which cancer-specific deubiquitinases of PTEN regulate its roles in the pathobiology of cancer, and new methods of pharmacologically for modulating PTEN deubiquitinases are critical areas of investigation for cancer treatment and prevention. Here, we assess the mechanisms and functions of deubiquitination as a recently appreciated mode of PTEN regulation and review the link between deubiquitinases and PTEN reactivation and its implications for therapeutic strategies.


Pioglitazone in clinical practice: where are we now?
Pioglitazone, a thiazolidinedione, improves insulin sensitivity and thus reduces blood glucose. Clinical trials have suggested potential cardiovascular outcome benefits in association with pioglitazone; however, safety concerns are mounting, with recent data suggesting a link between pioglitazone and an increased risk of bladder cancer. There is thus a growing focus on the risk-benefit profile of this agent and hence its potential role in the blood glucose-lowering treatment algorithm for people with type 2 diabetes. There are clear potential outcome benefits associated with pioglitazone. In this review, the authors focus on putting the true risk-benefit profile of pioglitazone into context based on critical appraisal of the currently available evidence.