Nesprin-2G knockout fibroblasts exhibit reduced migration, changes in focal adhesion composition, and reduced ability to generate traction forces.
The nuclear envelope protein nesprin-2G is a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex and is responsible for mechanical and signaling crosstalk between the nucleus and cytoskeleton. A prior study has demonstrated that nesprin-2G knockout mice show delayed wound healing. The goal was to elucidate the mechanism underlying the delayed wound closure in this mouse model. Primary fibroblasts from wild-type and knockout neonatal mice were isolated. Knockout cells exhibited decreased focal adhesion (FA) size, number, and intensity. Consistent with this result, FA protein expression levels were decreased in knockout cells. Additionally, knockout fibroblasts displayed an abnormal actin cytoskeleton, as evidenced by loss of TAN line formation and both cytoplasmic and peri-nuclear actin staining. Using collective and single cell motility assays, it was found that knockout cells exhibited a reduction in both speed and directed migration. Traction force microscopy revealed that knockout fibroblasts generated fewer traction forces compared with WT fibroblasts. In summary, the data indicated that changes in actin organization and defects in FAs result in a reduced ability of knockout fibroblasts to generate traction forces needed for efficient motility.


Stimulation of DNA synthesis in primary rat hepatocyte cultures by liver tumor promoters: interactions with other growth factors.
Mechanism(s) of tumor promotion in liver by xenobiotics such as hexachlorocyclohexane (HCH), 1,1,1-trichloro-2,2-bis (4-chlorophenyl)ethane (DDT) and phenobarbital (PB) are not understood in detail although growth-stimulatory effects may be significant in their action. As a basis for studying mechanisms of growth control by liver tumor promoters, effects of xenobiotics on DNA synthesis have been examined in primary cultures of normal rat hepatocytes, maintained under fully-defined conditions. The xenobiotics alone were relatively ineffective but they exhibited synergism with epidermal growth factor (EGF), insulin and dexamethasone in stimulating DNA synthesis and were effective in moderate-to-low density cultures but not in confluent monolayers. Under conditions optimized for HCH or pregnenolone 16 alpha-carbonitrile (PCN) (i.e. subconfluent cultures exposed to insulin, EGF and dexamethasone), HCH, PCN, DDT or PB caused a transient stimulation of DNA synthesis, apparent after 2 days in culture. This probably reflected earlier entry of hepatocytes to S-phase. HCH was shown to increase total DNA, total numbers of nuclei and numbers of cells undergoing mitosis per culture. In optimized conditions, HCH or PCN were about additive with norepinephrine, dialyzed serum or pyruvate or with a small effect of tri-iodothyronine in stimulating DNA synthesis. Although conditions optimal for HCH or PCN were not necessarily optimal for detecting growth-stimulatory effects of other xenobiotics or steroids, these culture conditions were shown to support stimulation of DNA synthesis by a variety of known liver tumor promoters including barbiturates, estrogens, progestins, peroxisomal proliferators and bile acids. Several compounds known not to promote liver carcinogenesis failed to stimulate DNA synthesis in similar hepatocyte cultures.


Direct Root Penetration and Rhizome Vascular Colonization by Fusarium oxysporum f. sp. cubense are the Key Steps in the Successful Infection of Brazil Cavendish.
Fusarium wilt of banana, which is caused by Fusarium oxysporum f. sp. cubense, is one of the most serious diseases of banana. F. oxysporum f. sp. cubense race 1 (Foc1) and race 4 (Foc4) are the most prevalent pathogens of banana cultivars in the world. To understand the differences in the infection processes between Foc1 and Foc4, green fluorescent protein-tagged strains of F. oxysporum f. sp. cubense tropical race 4 (FocTR4) and Foc1 were used to inoculate 'Brazil Cavendish' banana. At 2 days postinoculation (dpi), it was observed that the spores and hyphae of both Foc1 and Foc4 attached to the root hairs and root epidermis. At 3 dpi, the hyphae of both Foc1 and Foc4 were found in the vascular tissues of roots. However, Foc4 was observed in the parenchymal cells of banana root, whereas Foc1 was not found in parenchymal cells at 7 dpi. Furthermore, few Foc1 hyphae were observed in a few xylems whereas many more Foc4 hyphae were present in many xylems and phloems. Foc4 was observed in the vascular tissues of banana rhizomes, whereas no Foc1 was found in rhizomes 2 months after inoculation. The attachment process in F. oxysporum f. sp. cubense infection was further studied with scanning electron microscopy. Foc4 was observed to penetrate into banana roots from the intercellular space of the epidermis and wounds, whereas Foc1 mainly penetrated from the wounds but not from the intercellular space of the epidermis. Therefore, direct root penetration and rhizome vascular colonization by F. oxysporum f. sp. cubense are the key steps in the successful infection of Brazil Cavendish.


Modulation of feeding by endogenous sugar acids acting as hunger or satiety factors.
Endogenous sugar acids, 3,4-dihydroxybutanoic acid (2-deoxytetronic acid, 2-DTA) and 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid, 3-DPA), have been identified in the serum of fasted rats. Effects of these sugar acids on rat feeding behavior and neuron activity were investigated. Injections of 2-DTA (2.5 mumol) into the third cerebral ventricle of chronic rats suppressed food intake and single-neuron activity in the lateral hypothalamic area (LHA). Food consumption was reduced for 24 h, even in 72-h food-deprived rats. The same amounts of 3-DPA elicited feeding and increased LHA single-neuron activity with latencies of 6-8 min. Electrophoretically applied 2-DTA significantly and specifically suppressed activity of glucose-sensitive neurons in the LHA, whereas 3-DPA facilitated the activity. Nonglucose-sensitive LHA neurons were not affected by these sugar acids. The high correlation between modulation of feeding behavior and changes in LHA neuron activity after injection of these sugar acids suggested that 2-DTA may act as an endogenous satiety substance and 3-DPA as a hunger substance. The effects may be mediated through glucose-sensitive neurons in the LHA.


The effects of intervention on quality of telephone triage at an emergency unit in Finland: Nurses' perspective.
The aim of this study was to investigate the effects of a nurse training intervention on the assessment of patients' care needs in telephone triage at an emergency unit. The objective of this study was to generate information about nurse training that can be utilized when developing telephone triage and health care education. With the growing number of patients coming into emergency departments and a lack of resources in healthcare, it would be valuable to determine an effective training intervention in telephone triage, particularly when assessing the training needs of nurses. The study was quasi-experimental, with a pre- and post-test design. The data were collected from the nurses at the emergency department and joint emergency service of the Central Hospital in Northern Finland (baseline n = 28, post-test n = 26). The descriptive statistic, Fisher's χ(2) test and McNemar's test were used to analyse the data. The intervention improved nurses' skills to evaluate patients' needs and health condition via the telephone triage. There was a statistically significant difference in the resources, knowledge, skills and attitudes of the nurses between the baseline and post-test measurements. The nurse training intervention improved the quality of telephone triage. Nurses should receive continuous training in telephone triage in order to maintain and reinforce their professional competence. When planning the training, the age and relevant work experience of the nurses should be taken into consideration as well, since the results indicate that they lead to variation in the nurses' competence.


Optimal management of urinary tract infections in older people.
Urinary tract infections (UTI) occur frequently in older people. Unfortunately, UTI is commonly overdiagnosed and overtreated on the basis of nonspecific clinical signs and symptoms. The diagnosis of a UTI in the older patient requires the presence of new urinary symptoms, with or without systemic symptoms. Urinalysis is commonly used to diagnose infection in this population, however, the evidence for its use is limited. There is overwhelming evidence that asymptomatic bacteriuria should not be treated. Catheter associated urinary tract infection accounts for a significant amount of hospital-associated infection. Indwelling urinary catheters should be avoided where possible and alternatives sought. The use of narrow spectrum antimicrobial agents for urinary tract infection is advocated. Local guidelines are now widely used to reflect local resistance patterns and available agents. Guidelines need to be updated to reflect changes in antimicrobial prescribing and a move from broad to narrow spectrum antimicrobials.


Macrophage phenotype in mice deficient in both macrophage-colony-stimulating factor (op) and apolipoprotein E.
Mice deficient in both macrophage-colony-stimulating factor (M-CSF, op) and apolipoprotein E (apoE) have elevated cholesterol levels but are protected from atherosclerosis. To assess the contribution of macrophage (Mphi) phenotypic heterogeneity and scavenger receptor (SR-A) expression to this seeming paradox, we characterized the Mphi phenotype by immunohistochemistry in these animals. Lesion size was determined in animals fed a chow or Western-type diet, and lipoprotein clearance studies were performed in vivo. Op0/E0 mice have fourfold smaller aortic root lesions than op2/E0 animals despite 2.5-fold higher total plasma cholesterol levels. Mphis in atherosclerotic lesions of op2/E0 mice constitute a predominantly recruited and M-CSF-dependent population. In addition, Mphis in different locations in plaques show phenotypic heterogeneity. SR-A expression in op0/E0 mice is reduced in proportion to the decrease in Mphi numbers, and M-CSF is thus not an essential requirement for SR-A expression in vivo. M-CSF-deficient mice degrade injected AcLDL , showing an adequate level of SR-A activity present in vivo. In contrast, beta-VLDL clearance in op0/E0 mice is decreased, implicating monocytes/Mphis in its catabolism. There is prominent lipid accumulation in op2/E0 Kupffer cells and hepatocytes but not in M-CSF-independent Kupffer Mphis from op0/E0 mice. SR-A, while abundantly expressed on both Kupffer cells and sinusoidal endothelial cells in op2/E0 mice, remains mainly on sinusoidal endothelial cells in op0/E0 mice. This may explain preservation of SR-A activity in these animals. Our findings clearly illustrate the importance of both M-CSF and M-CSF-dependent monocytes/Mphis in maintaining cholesterol homeostasis and in atherogenesis.


Improving patient-centered care for HIV and mental illness: exploring hospital and community integration through education.
Current models of care delivery are failing patients with complexity, like those living with HIV, mental illness and other psychosocial challenges. These patients often require resource-intensive personalized care across hospital and community settings, but available supports can be fragmented and challenging to access and navigate. To improve this, the authors created a program to enhance integrated, trauma-informed care through an innovative educational role for a HIV community caseworker embedded in an academic HIV Psychiatry clinic, called the Mental Health Clinical Fellowship. Through qualitative interviews with 21 participants (patients, physicians, clinicians and Mental Health Clinical Fellows) from October 2020-March 2023, the authors explore how implementation of this program affects patient experiences and satisfaction with care. Patients described their care experiences as less stigmatizing, more accessible, holistic and coordinated. They often attributed this to the integration between fellow and psychiatrist, and specifically the accessible stance of community organizations embedded within a hospital, which helped build trust. Interchangeable and integrated support by caseworker and psychiatrist improved patient engagement in psychiatric management and patient satisfaction with their care. Cross-context and cross-disciplinary care provision that includes providers from community and hospital working directly together to deliver care can improve care for patients with significant complexity.


The quantitative impact of read mapping to non-native reference genomes in comparative RNA-Seq studies.
Sequence read alignment to a reference genome is a fundamental step in many genomics studies. Accuracy in this fundamental step is crucial for correct interpretation of biological data. In cases where two or more closely related bacterial strains are being studied, a common approach is to simply map reads from all strains to a common reference genome, whether because there is no closed reference for some strains or for ease of comparison. The assumption is that the differences between bacterial strains are insignificant enough that the results of differential expression analysis will not be influenced by choice of reference. Genes that are common among the strains under study are used for differential expression analysis, while the remaining genes, which may fail to express in one sample or the other because they are simply absent, are analyzed separately. In this study, we investigate the practice of using a common reference in transcriptomic analysis. We analyze two multi-strain transcriptomic data sets that were initially presented in the literature as comparisons based on a common reference, but which have available closed genomic sequence for all strains, allowing a detailed examination of the impact of reference choice. We provide a method for identifying regions that are most affected by non-native alignments, leading to false positives in differential expression analysis, and perform an in depth analysis identifying the extent of expression loss. We also simulate several data sets to identify best practices for non-native reference use.


Regional differences in constituents of gall stones.
The pathogenesis of pigment and mixed gall stone formation remains elusive. The elemental constituents of gall stones from southern states of Tamil Nadu, Kerala and Karnataka have been characterized. Our aim was to determine the elemental concentration of representative samples of pigment, mixed and cholesterol gall stones from Andhra Pradesh using proton-induced X-ray emission (PIXE) using a 3 MV horizontal pelletron accelerator. Pigment gall stones had significantly high concentrations of copper, iron and lead; chromium was absent. Except for iron all these elements were significantly low in cholesterol gall stones and intermediate levels were seen in mixed gall stones. Highest concentrations of chromium was seen in cholesterol and titanium in mixed gall stones respectively; latter similar to other southern states. Arsenic was distinctly absent in cholesterol and mixed gall stones. The study has identified differences in elemental components of the gall stones from Andhra Pradesh.


Spatially extended versus frontal cerebral near-infrared spectroscopy during cardiac surgery: a case series identifying potential advantages.
Stroke due to hypoperfusion or emboli is a devastating adverse event of cardiac surgery, but early detection and treatment could protect patients from an unfavorable postoperative course. Hypoperfusion and emboli can be detected with transcranial Doppler of the middle cerebral artery (MCA). The measured blood flow velocity correlates with cerebral oxygenation determined clinically by near-infrared spectroscopy (NIRS) of the frontal cortex. We tested the potential advantage of a spatially extended NIRS in detecting critical events in three cardiac surgery patients with a whole-head fiber holder of the FOIRE-3000 continuous-wave NIRS system. Principle components analysis was performed to differentiate between global and localized hypoperfusion or ischemic territories of the middle and anterior cerebral arteries. In one patient, we detected a critical hypoperfusion of the right MCA, which was not apparent in the frontal channels but was accompanied by intra- and postoperative neurological correlates of ischemia. We conclude that spatially extended NIRS of temporal and parietal vascular territories could improve the detection of critically low cerebral perfusion. Even in severe hemispheric stroke, NIRS of the frontal lobe may remain normal because the anterior cerebral artery can be supplied by the contralateral side directly or via the anterior communicating artery.


Time-dependent conformational change of thrombin molecules induced by sulfated polysaccharides.
Dextran sulfate (DS) had a greater ability to elute thrombin adsorbed on a small Sepharose 6B column than heparin did, while chondroitin sulfate A had little ability. It is probable that the strength of the interaction of thrombin depends mostly on the charge-density of strongly acidic sulfate groups in the polysaccharides. The change in intrinsic fluorescence intensity of thrombin with time was closely correlated with the rate of inactivation of the enzyme in the presence of sulfated polysaccharides. Both rates were affected by the pH of the solution in the presence of the polyanions. The rates in the presence of DS were highest at pH 6.05 among the three pHs tested, while they were enhanced only at pH 6.05 by heparin, but not by chondroitin sulfate A. Therefore, extensive charge-neutralization of thrombin by the sulfated polysaccharides is able to induce time- and temperature-dependent intramolecular conformational change (irreversible denaturation) of the enzyme molecules.


EPIZOO: a computer software package of methods for animal population health analysis and programming.
An animal population health and disease software package entitled 'EPIZOO' has been developed. This computer program comprises an integral and complex system of selected indicators contained in ten modules and over one hundred sub-programs, with approximately two hundred methods for use in problem solving, training and simulation. This fully user-friendly software is applicable to any animal disease, and makes analysis and programming easier and quicker. The software includes general methods for use in a number of fields: animal population health and disease situation (structure, dynamics, diagnosis, analysis and consequences) animal population characteristics of epizootiological importance animal health programme preparation, cost calculation and evaluation selected sampling other statistical procedures. EPIZOO is a relatively simple tool for field and management veterinarians, as well as veterinary students.


Giant Cell Tumor of the Calcaneus.
A 17-year-old female presented to us with pain and swelling in the right heel. Examination revealed the swelling to be tender, hard and fixed to the calcaneus. Radiographs showed an expansile, lytic lesion of the calcaneus with well-defined margins and no extraosseus spread. A core biopsy was done which showed multinucleated giant cells in a sea of mononuclear stromal cells, suggestive of a giant cell tumour (GCT). Curettage and filling up of the defect with bone cement was done under anaesthesia. The patient was fully ambulatory three months after the surgery. At two-year follow-up, the patient continued to be asymptomatic and radiographs revealed no signs of recurrence. It is important to note that GCT can occur in these rare sites and unusual age groups, and hence requires a good level of awareness of the surgeon and adequate preoperative workup, including biopsy, before proceeding to the definitive treatment of the lesion. Considering its potential local aggressiveness, early intervention is necessary. The patient should be kept under regular follow-up to detect any recurrence or metastasis in early stage.


Determination of factors influencing tobacco consumption in Turkey using categorical data analyses1.
The aim of this study is to specify factors influencing tobacco consumption in Turkey, which belongs to developing countries group, and to determine the extent of their influence. Factors related to the sociodemographic, economic, personal, environmental, and healthy life indicators influencing tobacco consumption in Turkey were determined using logistic and probit regression analyses. According to the results of the study, age, gender, education, marital status, fruit consumption, exposure to tobacco smoke at home, and frequent of alcohol consumption are the most influential variables effecting tobacco consumption. More effective results in policies aimed at preventing tobacco consumption can be accomplished by giving priority to individuals more inclined to tobacco consumption. People in 25-44 age group, men, graduates of high school and its equivalents, divorced/widowed individuals, individuals exposed to tobacco smoke, and alcohol users are individuals who tend to use tobacco.


Hormonal regulation of messenger ribonucleic acids for P450scc (cholesterol side-chain cleavage enzyme) and P450c17 (17 alpha-hydroxylase/17,20-lyase) in cultured human fetal adrenal cells.
ACTH has acute and long term effects on adrenal steroidogenesis by week 14 of fetal life. We used human fetal adrenal cells to investigate the long term effect of physiological doses of ACTH on mRNAs for P450scc (the cholesterol side-chain cleavage enzyme) and P450c17 (17 alpha-hydroxylase/17,20-lyase). Monolayer cultures of 18- to 24-week gestation fetal zone adrenal cells were maintained in the presence and absence of 10(-9) or 10(-8) M ACTH for up to 12 days. As assessed by RNA dot blots probed with cloned homologous human cDNAs, ACTH increased P450scc and P450c17 mRNAs 4- and 9-fold, respectively, over control values on day 7 of culture. ACTH-mediated stimulation was slightly less on day 12 of culture. The ACTH-mediated accumulation of those mRNAs were time dependent. When cells were exposed to a single 10(-8)-M dose of ACTH, the amount of P450scc and P450c17 mRNA was increased by 24 h, reaching a maximum at 48 h and diminishing by 72 h. When cells were maintained in 10(-8) M ACTH continuously, mRNA for both enzymes accumulated in a similar pattern, reaching a peak at 48 h but remaining at nearly maximal values thereafter, up to 96 h. Dibutyryl cAMP (10(-3) M) mimicked these stimulatory actions of ACTH, although its effect was greater at 24 h and more stable up to 96 h. Angiotensin II (1-100 ng/mL) and hCG (1-100 ng/mL) had no effect on accumulation of P450scc and P450c17 mRNAs. The production of both dehydroepiandrosterone sulfate and cortisol also was stimulated by ACTH, suggesting that the increased mRNAs were translated into active enzymes. These results indicate that ACTH induces human fetal adrenal cells to accumulate mRNAs for both P450scc and P450c17; this effect of ACTH is probably mediated by cAMP. Chronic 96-h stimulation of human fetal adrenal cells did not diminish their responsiveness to ACTH. Together with our earlier studies of the human fetal adrenal, these data indicate that fetal adrenal tissue does not exhibit the desensitization to trophic hormone stimulation characteristic of adult tissue.


Characterization of antibiotic resistance in commensal bacteria from an aquaculture ecosystem.
The objective of the study was to improve the understanding of antibiotic resistance (AR) ecology through characterization of antibiotic-resistant commensal isolates associated with an aquaculture production system. A total of 4767 isolates non-susceptible to sulfamethoxazole/trimethoprim (Sul/Tri), tetracycline (Tet), erythromycin (Erm), or cefotaxime (Ctx), originated from fish, feed, and environmental samples of an aquaculture farm with no known history of antibiotic applications were examined. Close to 80% of the isolates exhibited multi-drug resistance in media containing the corresponding antibiotics, and representative AR genes were detected in various isolates by PCR, with feed isolates had the highest positive rate detected. Identified AR gene carriers involved 18 bacterial genera. Selected AR genes led to acquired resistance in other bacteria by transformation. The AR traits in many isolates were stable in the absence of selective pressure. AR-rich feed and possibly environmental factors may contribute to AR in the aquaculture ecosystem. For minimum inhibitory concentration test, brain heart infusion medium was found more suitable for majority of the bacteria examined than cation-adjusted Mueller Hinton broth, with latter being the recommended medium for clinical isolates by standard protocol. The data indicated a need to update the methodology due to genetic diversity of microbiota for better understanding of the AR ecology.


Canine interdigestive and postprandial gallbladder motility and emptying.
The objectives of this study were to characterize intraluminal gallbladder pressure during fasting and postprandially and to determine the relationships between its intraluminal pressure and emptying. Conscious dogs, with chronic indwelling gallbladder and duodenal catheters to measure pressures and infuse nonabsorbable markers, were used to quantify intraluminal pressures and emptying of gallbladder contents and bile into the duodenum during interdigestive and postprandial periods. During the interdigestive period, a brief rise in intragallbladder pressure followed by the flow of bile and 20% of gallbladder marker into the duodenum occurred only during phase II (a period of irregular duodenal contractility preceded by absent duodenal activity, phase I, and followed by a period of regular duodenal contractility, phase III). We suggest that intragallbladder pressure increased secondary to contraction of the gallbladder against a closed sphincter of Oddi and its decline to base line was accompanied by sphincter relaxation, partial gallbladder emptying, and flow of bile into the duodenum. Postprandially, intragallbladder pressure transiently increased and was followed by an isotonic phase lasting 74 +/- 12 min that ended with the onset of rhythmic large-amplitude pressure elevations that continued for 5.1 +/- 1.6 h. Gallbladder emptying was most rapid during the first 30 min postprandially and was completed by 2 h. Thereafter, large-amplitude gallbladder pressure elevations may prevent gallbladder filling and divert hepatic bile into the duodenum until return of the fasting pattern.


Investigation on clotting and hemolysis characteristics of heparin-immobilized polyether sulfones biomembrane.
In this study, a novel heparin-immobilized polyethersulfone (PES) was synthesized. PES was initially sulfonated with chlorosulfonic acid and then 1,6-hexanediamine was grafted to the -SO(3)H groups of sulfonated PES, which subsequently reacted with heparin through a covalent bond by using (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC) as catalyst. The hydrophobic/hydrophilic property was characterized by measuring the water contact angle. The data shows decline from 62.29 degrees +/- 1.2 degrees to 47.86 degrees +/- 0.3 degrees for water and 86.79 degrees +/- 0.8 degrees to 68.34 degrees +/- 1.0 degrees for glycerol, which indicates an enhancement of hydrophilicity. Plasma hemolysis assay shows a comparatively low hemolysis ratio of 1.04%, which is below permissible limit of 5%. A higher content of dissociated blood cells and Ca(2+) concentration was found in red blood cell counting and coagulation factor IV test in heparinized PES. Plasma recalcification time of 360 s also offers positive evidence that heparinized PES seems to have a good anticoagulation property. This new heparin-immobilized PES biomaterials may have the potential for biomedical applications.


Resource stratified guidelines for cancer: Are they all the same? Interguideline concordance for systemic treatment recommendations.
A number of organizations are producing resource stratified guidelines (RSGs) for cancer. Despite using similar definitions of resource levels, systemic treatment recommendations often differ between organizations. We systematically searched for RSGs focusing on solid tumors. We qualitatively compared the methods used to generate guidelines using the AGREE-II appraisal tool. We extracted systemic treatment recommendations and assessed interguideline concordance using the Gwet AC1 coefficient, stratified by resource level, treatment setting and cancer type. We identified 69 RSGs cancer covering 15 solid tumors produced by four organizations. Despite using common resource-level definitions (Basic, Core/Limited, Enhanced and Maximal), recommendations differed between organizations. Concordance for chemotherapy recommendations was poor in Basic (58.3%, Gwet 0.20), fair in Core (58.3%, Gwet 0.32) and excellent in Enhanced (92.4%, Gwet 0.92) and Maximal settings (95.4%, Gwet 0.95). Concordance rates for endocrine therapy were good in Basic (80% Gwet 0.61), and excellent in Core (90%, Gwet 0.87), Enhanced (90%, Gwet 0.89) and Maximal settings (90%, Gwet 0.89). There was moderate to excellent concordance in targeted therapy recommendations across all resource levels. Differences in recommendations appeared driven by different opinions among the chosen panel of experts regarding what is resource appropriate. Overall, we found that countries looking to base treatment and health-policy on RSGs will find conflicting information depending on which guidelines are used, particularly for chemotherapy in Basic and Core settings. Improved transparency regarding the methods used to determine the value of a therapy for a given resource level is needed.


Compartmentalization of information processing in an aplysia feeding circuit interneuron through membrane properties and synaptic interactions.
We describe a pair of cerebral-to-buccal interneurons, CBI-5/6, which have outputs and inputs in two ganglia. The soma in the cerebral ganglion received synaptic inputs during buccal motor programs (BMPs) and after mechanical stimulation of the lips. During BMPs the soma received antidromic spikes generated in processes in the buccal ganglion. The soma was driven into a plateau potential by each of these inputs, during which it fired orthodromically at 0-5 Hz. The soma had outputs in the cerebral ganglion consisting of electrical coupling to the adjacent CBI-5/6 and to a cerebral-to-pedal neuron (CPN1). The buccal terminals of CBI-5/6 received inputs that generated rhythmic barrages (up to 25 Hz) of antidromic spikes during BMPs. The buccal terminals had chemical and electrical outputs to motor and premotor elements of feeding circuitry. This combination of synaptic interactions and endogenous properties mean that CBI-5/6 can process information in a number of ways. During the barrage of antidromic spikes, high-frequency firing will produce strong inputs to buccal followers and on their arrival at the soma will transfer excitation electrotonically to CPN1. Subthreshold input to the soma will be transferred electrotonically to cerebral followers but will not be relayed to postsynaptic buccal neurons. Plateau potentials after the antidromic spikes or local cerebral inputs will locally excite CPN1 via electrical coupling but will have little influence on buccal events because of the low orthodromic firing rate. Thus, CBI-5/6 may transmit information locally within the cerebral ganglion or more extensively in both buccal and cerebral ganglia simultaneously.


[Depression Among Caregivers of HIV - Positive Injection Drug Users in Hanoi, 2016].
Most of people who inject drugs in Vietnam live in their family homes and these living have formed the burden on caring. This study aimed at exploring the characteristic of depression of caregivers of HIV - positive injection drug users and relative factors. Cross - sectional assessment data were gathered from 138 caregivers recruited from Hanoi city. About 20% of the study sample had a depressed condition from mild to extremely severe. Caregiver burden and family function were significantly associated with depression of caregivers. This study addressed the needs of intervention to improve family function and to decrease caregiver burden aimed at raising mental health of caregivers of HIV - positive injection drug users.


Major Incident Hospital Simulations in Hospital Based Health Care: A Scoping Review.
Major incidents are occurring in increasing frequency, and place significant stress on existing health-care systems. Simulation is often used to evaluate and improve the capacity of health systems to respond to these incidents, although this is difficult to evaluate. A scoping review was performed, searching 2 databases (PubMed, CINAHL) following PRISMA guidelines. The eligibility criteria included studies addressing whole hospital simulation, published in English after 2000, and interventional or observational research. Exclusion criteria included studies limited to single departments or prehospital conditions, pure computer modelling and dissimilar health systems to Australia. After exclusions, 11 relevant studies were included. These studies assessed various types of simulation, from tabletop exercises to multihospital events, with various outcome measures. The studies were highly heterogenous and assessed as representing variable levels of evidence. In general, all articles had positive conclusions with respect to the use of major incidence simulations. Several benefits were identified, and areas of improvement for the future were highlighted. Benefits included improved understanding of existing Major Incident Response Plans and familiarity with the necessary paradigm shifts of resource management in such events. However, overall this scoping review was unable to make definitive conclusions due to a low level of evidence and lack of validated evaluation.


Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF-IRF4 transcription factor complex.
Variable strengths of signaling via the T cell antigen receptor (TCR) can produce divergent outcomes, but the mechanism of this remains obscure. The abundance of the transcription factor IRF4 increases with TCR signal strength, but how this would induce distinct types of responses is unclear. We compared the expression of genes in the TH2 subset of helper T cells to enhancer occupancy by the BATF-IRF4 transcription factor complex at varying strengths of TCR stimulation. Genes dependent on BATF-IRF4 clustered into groups with distinct TCR sensitivities. Enhancers exhibited a spectrum of occupancy by the BATF-IRF4 ternary complex that correlated with the sensitivity of gene expression to TCR signal strength. DNA sequences immediately flanking the previously defined AICE motif controlled the affinity of BATF-IRF4 for direct binding to DNA. Analysis by the chromatin immunoprecipitation-exonuclease (ChIP-exo) method allowed the identification of a previously unknown high-affinity AICE2 motif at a human single-nucleotide polymorphism (SNP) of the gene encoding the immunomodulatory receptor CTLA-4 that was associated with resistance to autoimmunity. Thus, the affinity of different enhancers for the BATF-IRF4 complex might underlie divergent signaling outcomes in response to various strengths of TCR signaling.


Assessing medical student cultural competence: what really matters.
The study aimed to explore medical students' attitudes and beliefs toward Latino patients, specifically: to assess students' levels of knowledge, cultural competence, and comfort with Latinos; to determine students' exposure to and previous experience with Latinos; and to evaluate whether factors such as study abroad, living abroad, previous clinical experience with Latinos, and language proficiency predict Latino knowledge, cultural competence, and comfort with Latinos. This study utilized a cross-sectional survey design. Participants were third and fourth year medical students at three medical schools in the Southeastern United States. Three composite measures: Latino knowledge, Cultural competence, and Comfort with Latino patients, were predicted in a multivariate regression model including individual sociodemographic characteristics and past clinical or social experience with Latinos. A total of 170 medical students completed the survey (43% response rate). Spanish language proficiency was a statistically significant predictor (t(131)=2.72, p<0.05) of Latino knowledge. Social interaction with Latinos in the past year (t(126)=3.09, p<0.01), ever having lived in a Spanish-speaking country (t(126)=2.86, p<0.01), and Spanish language proficiency (t(126)=3.28, p<0.01) independently predicted cultural competence. Previous clinical experience with Latinos was not significantly associated with the three composite dependent variables, and comfort with Latino patients was not significantly predicted by any of the six Latino-related explanatory variables. Factors prior to medical school matriculation and during medical education may contribute to increased cultural competence and comfort with multicultural patients. Cultural patient-partner programs may be an effective way to increase cultural competence within the confines of medical school curricula.


High-power single transverse and polarization mode VCSEL for silicon photonics integration.
We demonstrate a 6.5 mW single transverse and polarization mode GaAs-based oxide-confined VCSEL at 850 nm. High power is enabled by a relatively large oxide aperture and an epitaxial design for low resistance, low optical loss, and high slope efficiency VCSELs. With the oxide aperture supporting multiple polarization unrestrained transverse modes, single transverse and polarization mode operation is achieved by a transverse and polarization mode filter etched into the surface of the VCSEL. While the VCSEL is specifically designed for light source integration on a silicon photonic integrated circuit, its performance in terms of power, spectral purity, polarization, and beam properties are of great interest for a large range of applications.


Epidermal tumour necrosis factor alpha and interleukin 6-like activities in AIDS-related Kaposi's sarcoma. An immunohistological study.
Biopsies from 6 patients with AIDS and Kaposi's sarcoma (KS) in the tumour stage, and 6 healthy controls, were immunohistologically examined for the presence of tissue-bound tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) in the skin. TNF alpha was demonstrated using specific polyclonal antiserum to human recombinant TNF alpha. IL-6 was visualized indirectly using a polyclonal antiserum to partially purified human crude supernatants of activated human blood monocytes, followed by absorption with recombinant human IL-6. The cytokines were found identically located in epidermal cell membranes in stratum granulosum and spinosum of the epidermis from unaffected skin in both AIDS patients and in controls. Biopsies from KS elements showed markedly increased epidermal staining for both TNF delta and IL-6. It was not possible to detect TNF alpha or IL6 in the endothelial cells of the tumour. The observation of increased amounts of epidermal-bound TNF alpha and IL-6 in AIDS-related KS elements supplements previous studies indicating that the skin plays an active immunoinflammatory role in patients with AIDS.


The reporting of cytologic smears. Selected problems with morphologic terms.
PROBLEMS ARISE WHEN MORPHOLOGIC TERMINOLOGY FALLS INTO CATEGORIES WHICH: (1) Utilize numbers to replace words and (2) utilize words of such indeterminate meaning that definition depends entirely upon local usage.We should strive to replace any means of diagnosis that does not convey specificity with means capable of precision. The major criterion for the suitability of a diagnostic system is that it is universally understood and is precise enough to result in optimal patient management. Meeting those demands requires the use of nomenclature in cytology that approximates, as far as possible, the actual tissue diagnosis.


Lipoteichoic acid and toll-like receptor 2 internalization and targeting to the Golgi are lipid raft-dependent.
Lipoteichoic acid (LTA), a key cell wall component of Gram-positive bacteria, seems to function as an immune activator with characteristics very similar to lipopolysaccharide from Gram-negative bacteria. It has been shown that LTA binds CD14 and triggers activation via Toll-like receptor 2, but whether the activation occurs at the cell surface or internalization is required to trigger signaling has yet to be demonstrated. In this work we have investigated LTA binding and internalization and found that LTA and its receptor molecules accumulate in lipid rafts and are subsequently targeted rapidly to the Golgi apparatus. This internalization seems to be lipid raft-dependent because raft-disrupting drugs inhibited LTA/Toll-like receptor 2 colocalization in the Golgi. Similarly to lipopolysaccharide, LTA activation occurs at the cell surface, and the observed trafficking is independent of signaling.


Cooperative Virus-Virus Interactions: An Evolutionary Perspective.
Despite extensive evidence of virus-virus interactions, not much is known about their biological significance. Importantly, virus-virus interactions could have evolved as a form of cooperation or simply be a by-product of other processes. Here, we review and discuss different types of virus-virus interactions from the point of view of social evolution, which provides a well-established framework for interpreting the fitness costs and benefits of such traits. We also classify interactions according to their mechanisms of action and speculate on their evolutionary implications. As in any other biological system, the evolutionary stability of viral cooperation critically requires cheaters to be excluded from cooperative interactions. We discuss how cheater viruses exploit cooperative traits and how viral populations are able to counteract this maladaptive process.


Metabolism of the glycosyl diglycerides and phosphatidylglucose of Staphylococcus aureus.
A glucose containing lipid, phosphatidylglucose (probably 3-sn-phosphatidyl-1'-glucose) and a lipid tentatively identified as phosphatidylethanolamine have been characterized in the lipids of Staphylococcus aureus. These lipids together comprise less than 2% of the total phospholipids of exponentially growing S. aureus and accumulate to 14% of the total phospholipid in stationary-phase cells. These lipids lost no (32)P when cells grown with H(3) (32)PO(4) were transferred to nonradioactive medium during the exponential growth phase. This was in marked contrast to the other phospholipids which lost (32)P rapidly. The loss of (32)P from phosphatidic acid and cardiolipin in exponentially growing cells was biphasic, suggesting heterogeneity of phospholipid phosphate metabolism. The mono- and diglucosyl diglycerides showed a rapid loss of (14)C-glucose during growth in nonradioactive medium but no loss of (14)C from the fatty acids of these lipids. The (14)C in the glucose and fatty acids of the glucosyl diglycerides was derived from glucose.


Coronary laser with simultaneous contrast injection for the treatment of stent underexpansion.
Stent underexpansion is a challenge in interventional cardiology. Some off-label treatments, such as rotational atherectomy, intravascular lithotripsy (IVL) and coronary lasing, have been used to overcome the problem. The purpose of this study is to evaluate the safety and efficacy of coronary laser atherectomy with simultaneous contrast injection and subsequent balloon dilation to optimize stent expansion. Coronary laser atherectomy with simultaneous contrast injection was used. After lasing, non-compliant balloon dilation at high pressure was performed to overcome the underexpanded point. The average increase in the minimum stent area (MSA) was measured by intravascular ultrasound (IVUS), and any complication related to the technique was evaluated. Additionally, major adverse cardiovascular events (MACE), consisting of death from any cause, new myocardial infarction (MI) and target lesion revascularization (TLR), were scrutinized in a long-term follow-up. Sixteen underexpanded stents were treated with laser between August 2017 and November 2022. In all cases but one, IVUS was used to evaluate the MSA before and after lasing. The MSA showed an average increase of 2.34 ± 1.57 mm² (95% confidence interval [CI]: 1.47-3.21; p < 0.001) after laser application and balloon inflation. No complication related to the technique was detected. During a follow-up period of a median (interquartile range) of 457 (50-973) days, the combined MACE assessed by Kaplan-Meier estimator showed an event-free rate of 0.82 (95% CI: 0.59-1). Coronary laser with simultaneous contrast injection is a safe method to optimize a stent underexpansion, with an acceptable event-free rate in long-term follow-up.


Assembled surface-anisotropic colloids as a template for a multistage catalytic membrane reactor.
A polymeric catalytic membrane reactor (CMR) is fabricated using alternating assemblies of surface-anisotropic (sa-) and plain (p-) polystyrene (PS) colloids as a template. We report the preparation of TiO2 sa-PS colloids by physical vapor deposition of titanium onto a colloidal monolayer in an oxygen-rich environment and employ the modified colloids as a means to deliver the TiO2 catalyst to the CMR pores. sa-PS and p-PS colloids are assembled into alternating cylindrical sections inside a microcapillary followed by infiltration and curing of a liquid polymer precursor in the interstitial space of the assembly. Subsequent organic solvent treatment results in a cylindrical porous CMR with embedded TiO2 caps. TiO2 cap embedment, composition and surface morphology, surface pore structure, and cross-sectional integrity are analyzed using variable-pressure scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy.


Local recurrence of carcinoma of the tongue after glossectomy: patient prognosis.
We conducted a retrospective review of the prognosis for patients with local recurrence after surgical treatment of carcinoma of the tongue. Glossectomy for squamous cell carcinoma of the tongue was performed in 167 patients. Local recurrence developed in 32 patients including 21 with local recurrence alone, 10 with locoregional recurrence and one with locodistant recurrence. The incidence of local recurrence increased with tumor stage (from 16% of T1 tumors to 46% of T4 carcinomas). Eleven (34%) patients underwent surgical salvage for local recurrence, with only one (9%) patient surviving free of carcinoma at 43 months post-surgical salvage. All of the remaining 21 patients with local recurrence were treated palliatively and all died within one year. Patients who underwent surgical salvage had significantly higher survival rates compared to those treated palliatively. Close follow-up after glossectomy is important for early detection of local recurrence amenable to surgical salvage. However, the overall prognosis for patients with local recurrence was poor, with a three-year actuarial survival rate of only 3%. Therefore, prevention of local recurrence with adequate initial surgical treatment is essential.


Research progress in architecture and application of RRAM with computing-in-memory.
The development of new technologies has led to an explosion of data, while the computation ability of traditional computers is approaching its upper limit. The dominant system architecture is the von Neumann architecture, with the processing and storage units working independently. The data migrate between them via buses, reducing computing speed and increasing energy loss. Research is underway to increase computing power, such as developing new chips and adopting new system architectures. Computing-in-memory (CIM) technology allows data to be computed directly on the memory, changing the current computation-centric architecture and designing a new storage-centric architecture. Resistive random access memory (RRAM) is one of the advanced memories which has appeared in recent years. RRAM can change its resistance with electrical signals at both ends, and the state will be preserved after power-down. It has potential in logic computing, neural networks, brain-like computing, and fused technology of sense-storage-computing. These advanced technologies promise to break the performance bottleneck of traditional architectures and dramatically increase computing power. This paper introduces the basic concepts of computing-in-memory technology and the principle and applications of RRAM and finally gives a conclusion about these new technologies.


Chromosomal location of a gene for chemical longevity of messenger ribonculeic acid in a temperature-sensitive mutant of Escherichia coli.
Genetic analysis of a thermolabile mutation affecting alteration of messenger ribonculeic acid stability indicates that the gene ams maps close to pyrC gene (23 min) on the Escherichia coli chromosome and has a cotransduction frequency of 29.6% with pyrC gene. The probable gene order is pyrD-ams-pyrC-purB.


Teaching Basic Nursing Care: Nurse Preceptors' Perceptions about Changing the Teaching Context from the Clinical Setting to a School Simulation Lab.
Research demonstrates that basic nursing care receives less attention in clinical settings and has become visually less prominent in nursing education curriculums. While much is known about the importance of preceptorship in clinical settings, little is known about how preceptors teach basic nursing care to students in a school simulation lab. This study explores the preceptors' perceptions of teaching basic nursing care to nursing students in the school simulation lab compared to clinical settings. Data were collected through focus group interviews and participant observation and analyzed by using qualitative content analysis. Three main categories emerged: (i) Perceived advantages and disadvantages, (ii) Positive attitudes - remembering being a student, and (iii) Knowing what to do and showing how to do it. Awareness of the importance of having knowledge about basic nursing care may contribute to counterbalancing the devaluation of basic nursing care among nursing students.


Approximate treatment of higher excitations in coupled-cluster theory. II. Extension to general single-determinant reference functions and improved approaches for the canonical Hartree-Fock case.
The theory and implementation of approximate coupled-cluster (CC), in particular approximate CC singles, doubles, triples, and quadruples methods, are discussed for general single-determinant reference functions. While the extension of iterative approximate models to the non-Hartree-Fock case is straightforward, the generalization of perturbative approaches is not trivial. In contrast to the corresponding perturbative triples methods, there are additional terms required for non-Hartree-Fock reference functions, and there are several possibilities to derive approximations to these terms. As it turns out impossible to develop an approach that is consistent with the canonical Hartree-Fock-based theory, several new approximations have been implemented and their performance for total energies and heats of formation has been assessed. The numerical results show that the performance of the methods does not depend strongly on the approximations assumed. Furthermore, the new perturbative quadruples methods, when applied to canonical Hartree-Fock reference functions, outperform at least for absolute energies the existing ones without increasing the computational costs.


[Metabolic curietherapy with P-32 in bone metastases in breast cancer].
The administration of radioactive phosphorus (P-32) for the treatment of pain in metastatic bone lesions from breast cancer shows palliative effects lasting three to nine months. The evolution of the disease is not modified.


Erythropoietin and cancer: the unintended consequences of anemia correction.
Until 1990, erythropoietin (EPO) was considered to have a single biological purpose and action, the stimulation of red blood cell growth and differentiation. Slowly, scientific and medical opinion evolved, beginning with the discovery of an effect on endothelial cell growth in vitro and the identification of EPO receptors (EPORs) on neuronal cells. We now know that EPO is a pleiotropic growth factor that exhibits an anti-apoptotic action on numerous cells and tissues, including malignant ones. In this article, we present a short discussion of EPO, receptors involved in EPO signal transduction, and their action on non-hematopoietic cells. This is followed by a more detailed presentation of both pre-clinical and clinical data that demonstrate EPO's action on cancer cells, as well as tumor angiogenesis and lymphangiogenesis. Clinical trials with reported adverse effects of chronic erythropoiesis-stimulating agents (ESAs) treatment as well as clinical studies exploring the prognostic significance of EPO and EPOR expression in cancer patients are reviewed. Finally, we address the use of EPO and other ESAs in cancer patients.


Prevalence of Culturable Bacteria and Yeasts in the Nasopharynx Microbiota during the Physiological Course of Pregnancy.
The aim of the study was to compare the prevalence of the nasopharyngeal carriage of culturable microorganisms in the microbiota of asymptomatic women with a physiological pregnancy (PW) and nonpregnant women (NPW). Nasopharyngeal swabs were collected from 53 PW and 30 NPW to detect bacterial and fungal colonization. Isolates were identified using the culture method and the MALDI-TOF MS technique. The nasopharyngeal microbiota (NPM) partially differed between PW and NPW. These differences in the frequency of nasopharyngeal colonization between the PW and NPW groups were not statistically significant (p > 0.05); all cases were colonized by bacteria and only two cases in the PW group were colonized by yeasts, namely, Rhodotorula spp. High levels of staphylococcal colonization, including predominantly coagulase-negative staphylococci and S. aureus in the nasopharyngeal sample, were present in both groups. The reduced number of Gram-negative rods colonized in the cases studied was seen in samples from the NPW group, particularly with Enterobacterales, and anaerobic Cutibacterium spp. were isolated only in the PW group (p < 0.05). Moreover, a higher carriage rate of Enterobacter aerogenes colonization was statistically significant (p < 0.05) and correlated with the NPW group. Pregnancy may disturb the composition of the NPM represented by commensals and opportunistic bacteria and promote yeast colonization as compared to nonpregnant women.


Circular RNAs in vascular diseases.
Vascular diseases are the leading cause of morbidity and mortality worldwide and are urgently in need of diagnostic biomarkers and therapeutic strategies. Circular RNAs (circRNAs) represent a unique class of RNAs characterized by a circular loop configuration and have recently been identified to possess a wide variety of biological functions. CircRNAs exhibit exceptional stability, tissue specificity, and are detectable in body fluids, thus holding promise as potential biomarkers. Their encoding function and stable gene expression also position circRNAs as an excellent alternative to gene therapy. Here, we briefly review the biogenesis, degradation, and functions of circRNAs. We summarize circRNAs discovered in major vascular diseases such as atherosclerosis and aneurysms, with a particular focus on molecular mechanisms of circRNAs identified in vascular endothelial cells and smooth muscle cells, in the hope to reveal new directions for mechanism, prognosis and therapeutic targets of vascular diseases.


Cooperation and fairness depend on self-regulation.
Any evolved disposition for fairness and cooperation would not replace but merely compete with selfish and other antisocial impulses. Therefore, we propose that human cooperation and fairness depend on self-regulation. Evidence shows reductions in fairness and other prosocial tendencies when self-regulation fails.


Discrimination, Racial/Ethnic Identity, and Substance Use Among Latina/os: Are They Gendered?
Prior research suggests that stronger racial/ethnic identification offsets negative effects of discrimination on substance use. Yet research in this area and on whether gender modifies this association is limited for Latina/os. The purpose of the present study is to examine whether different sources of discrimination (everyday and racial/ethnic) are associated with substance use (alcohol use disorder, smoking), if racial/ethnic identity buffers this association, and the potential moderating role of gender among these variables. We present cross-sectional, US population-based data from the Latina/o adult sample (1427 females and 1127 males) of the National Latino and Asian American Study. Respondents completed self-reported measures of everyday and racial/ethnic discrimination, racial/ethnic identity, smoking status, and Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) lifetime alcohol use disorder. Weighted logistic regression analyses showed that before inclusion of three-way interactions and adjusting for covariates, everyday discrimination predicted increased risk for any DSM-IV lifetime alcohol use disorders. Moderation analyses revealed that the effect of everyday discrimination on the risk of being a current smoker was strongest for Latino men with high levels of racial/ethnic identity compared to those with low racial/ethnic identity. No differences were noted among Latino women. There were no main or interaction effects of racial/ethnic discrimination for any substance use outcome. Findings suggest differential associations for type of discrimination and outcome and that the role of racial/ethnic identity is gender-specific for smoking, appearing particularly detrimental for Latino men reporting high levels of racial/ethnic identity.


The mechanism of discordant xenograft rejection.
The mechanism of discordant xenograft rejection using the guinea pig-to-rat heart graft model was studied. In this model, we found that (A) Rejection occurred rapidly, in 17.5 +/- 8.3 min (mean +/- SD) (n = 8). (B) The graft survived longer when the recipient rat was pretreated with cobra venom facter (CVF). (C) Complement hemolytic titers in serum showed significant reduction of C3 in rejection without consumption of C4 and C2, suggesting complement activation through the alternative pathway. (D) No natural antibodies were detected in this combination. Complement-dependent cytotoxicity (CDC) titer, and hemagglutination (HA) titer were lower than x1. (E) Histological examination of the rejected heart xenograft revealed a large area of myocytolysis without interstitial cellular infiltration. (F) In vitro experiments showed that rat complement attacked guinea pig erythrocytes (Egp) via the alternative pathway. These findings indicate that rejection in this discordant xenograft model of guinea pig-to-rat was caused by primary activation of complement via the alternative pathway.


Disfluencies and phonological revisions in a nonword repetition task in school-age children who stutter.
Phonological encoding and associated functions, including monitoring of covert and overt speech, have been attributed relevant roles in stuttering. The aim of this study was to investigate these processes by testing the effects of nonword length in syllables (3-, 4-, 6-syllable), phonotactics, and phonemic/phonetic complexity on disfluencies and phonological revisions in 26 school-age children who stutter (CWS, n = 13) and matched fluent controls (CWNS). Participants repeated nonwords in two sessions separated by an hour. Within-group comparisons of percentage disfluencies using nonparametric tests resulted in significantly more disfluencies for the 6- compared to the 3-syllable nonwords and suggested that nonword length influences disfluencies in the CWS. The groups were comparable in the percentage of disfluencies at all levels of nonword length. The findings failed to provide conclusive evidence that phonological complexity and phonotactic manipulations have a greater effect on disfluencies in CWS compared to CWNS. The findings of significantly fewer phonological revisions and the lack of a significant correlation between disfluencies and revisions in the CWS in Session 1 compared to the CWNS are interpreted to suggest reduced external auditory monitoring. Demands on incremental phonological encoding with increasing task complexity (the Covert Repair Hypothesis, Postma & Kolk, 1993) and reduced external auditory monitoring of stuttered speech can account for the disfluencies, speech errors, and revisions in the speech of school-age CWS.


Comparative study of thylakoid membranes in terminal heterocysts and vegetative cells from two cyanobacteria, Rivularia M-261 and Anabaena variabilis, by fluorescence and absorption spectral microscopy.
Heterocyst is a nitrogen-fixing cell differentiated from a cell for oxygen-evolving photosynthesis (vegetative cell) in some filamentous cyanobacteria when fixed nitrogen (e.g., ammonia and nitrate) is limited. Heterocysts appear at multiple separated positions in a single filament with an interval of 10-20 cells in some genera (including Anabaena variabilis). In other genera, a single heterocyst appears only at the basal terminal in a filament (including Rivularia M-261). Such morphological diversity may necessitate different properties of heterocysts. However, possible differences in heterocysts have largely remained unexplored due to the minority of heterocysts among major vegetative cells. Here, we have applied spectroscopic microscopy to Rivularia and A. variabilis to analyze their thylakoid membranes in individual cells. Absorption and fluorescence spectral imaging enabled us to estimate concentrations and interconnections of key photosynthetic components like photosystem I (PSI), photosystem II (PSII) and subunits of light-harvesting phycobilisome including phycocyanin (PC). The concentration of PC in heterocysts of Rivularia is far higher than that of A. variabilis. Fluorescence quantum yield of PC in Rivularia heterocysts was found to be virtually the same as those in its vegetative cells, while fluorescence quantum yield of PC in A. variabilis heterocysts was enhanced in comparison with its vegetative cells. PSI concentration in the thylakoid membranes of heterocysts seems to remain nearly the same as those of the vegetative cells in both the species. The average stoichiometric ratio between PSI monomer and PC hexamer in Rivularia heterocysts is estimated to be about 1:1.


A worksite diabetes prevention program: two-year impact on employee health.
The purpose of this study was to determine the 2-year impact of a worksite-based diabetes prevention program. Thirty-seven pre-diabetic and previously undiagnosed diabetic employees participating in a 12-month worksite diabetes prevention program were included. Weight, body mass index, waist circumference, oral glucose tolerance testing, fasting insulin, blood lipids, and aerobic fitness had improved significantly after 6 months. Much of this improvement continued through 12 months. One year following the intervention, oral glucose tolerance and aerobic fitness had improved significantly. Of the 22 employees remaining in the study through 24 months, more than half had normal results on glucose tolerance testing. Worksite diabetes prevention programs may reduce blood glucose below pre-diabetic and diabetic levels. Improvements in diabetes risk factors persisted for at least 2 years in most of these employees.


Platelet and Red Blood Cell Indices in Patients with Panic Disorder: A Receiver Operating Characteristic Analysis.
Objective Panic disorder (PD) is associated with changes in platelet and red blood cell (RBC) indices. However, the diagnostic or predictive value of these indices is unknown. This study assessed the diagnostic and discriminating value of platelet and RBC indices in patients with PD. Materials and Methods In this cross-sectional study including patients with PD ( n = 98) and healthy controls ( n = 102), we compared the following blood indices: mean platelet volume (MPV), platelet distribution width (PDW), and RBC distribution width (RDW). The receiver operating characteristic (ROC) curve was used to calculate the area under the ROC curve (AUC), sensitivity, specificity, and likelihood ratio for the platelet and RBC indices. Results Statistically significant increase in PDW (17.01 ± 0.91 vs. 14.8 ± 2.06; p < 0.0001) and RDW (16.56 ± 2.32 vs. 15.12 ± 2.43; p < 0.0001) levels were observed in patients with PD. PDW and mean corpuscular hemoglobin concentration had larger AUC (0.89 and 0.74, respectively) and Youden's index (0.65 and 0.39, respectively), indicating their higher predictive capacity as well as higher sensitivity in discriminating patients with PD from healthy controls. Conclusion PDW can be considered a "good" diagnostic or predictive marker in patients with PD.


Phenylboronic Acid-Modified Near-Infrared Region II Excitation Donor-Acceptor-Donor Molecule for 2-Deoxy-d-Glucose Improved Starvation/Chemo/Photothermal Combination Therapy.
Synergistic chemotherapy and photothermal therapy (PTT) have emerged as a promising anticancer paradigm to achieve expected therapeutic effects while mitigating side effects. However, the chemo/PTT combination therapy suffers from limited penetration depth, thermoresistance performance of tumor cells, and low drug bioavailability. Herein, multifunctional nanoparticles (BTP/DOX/2DG NPs) coloaded with near-infrared region II (NIR-II) light excitation donor-acceptor-donor (D-A-D) small molecules, doxorubicin (DOX), and 2-deoxy-d-glucose (2-DG) are developed for reinforced starvation/chemo/NIR-II PTT combination therapy. The synthesized phenylboronic acid (PBA)-modified water-soluble D-A-D molecule (BBT-TF-PBA) not only exhibits high binding ability to DOX and 2-DG through donor-acceptor coordination interactions PBA-diol bonds but also serves as a photoactive agent for NIR-II fluorescence imaging, NIR-II photoacoustic imaging, and NIR-II PTT. Under the acidic and oxidizing conditions in the tumor microenvironment, donor-acceptor coordination interactions and PBA-diol bond are decomposed, simultaneously releasing DOX and 2-DG from BTP/DOX/2DG NPs to achieve effective chemotherapy and starvation therapy. 2-DG also effectively inhibits the expression of heat shock protein and further enhances NIR-II PTT and chemotherapy efficiency. In vitro and in vivo experiments demonstrate the combination effect of BTP/DOX/2DG NPs for chemotherapy, NIR-II PTT, and starvation therapy.


Comorbidities in idiopathic pulmonary fibrosis patients: a systematic literature review.
Idiopathic pulmonary fibrosis (IPF) is associated with a fatal prognosis and manifests in patients over 60 years old who may have comorbidities. The prevalence and impact of comorbidities on the clinical course of IPF is unclear.This systematic literature review examined the prevalence of comorbidities and mortality associated with comorbidities in IPF patients. Relevant observational studies published in English from January 1990 to January 2015 identified via MEDLINE and EMBASE were included; bibliographies of articles were also searched.Among the 126 studies included, prevalence of pulmonary hypertension (PH) was 3-86%, 6-91% for obstructive sleep apnoea, 3-48% for lung cancer and 6-67% for chronic obstructive pulmonary disease (COPD). Nonrespiratory comorbidities included ischaemic heart disease (IHD) (3-68%) and gastro-oesophageal reflux (GER) (0-94%). Mortality was highest among patients with IPF and lung cancer. Most studies assessed relatively small samples of patients with IPF.PH, COPD, lung cancer, GER and IHD are significant comorbidities; differences in IPF severity, case definitions and patient characteristics limited the comparability of findings. The identification and prompt treatment of comorbidities may have a clinically significant impact on overall outcome that is meaningful for patients with IPF.


Clinical trial of corticosteroid and beta-2 bronchodilator in acute wheezing infants.
To evaluate the effect of a combination of corticosteroid and beta-2 bronchodilator on acute, young, wheezing patients, a total of 80 patients, ages below 36 months who were hospitalized for this condition during the period November 1988 to March 1990 were studied. They were divided into three groups. Group A consisted of 29 cases, under 12 months old, and treated with hydrocortisone and procaterol; Group B included 23 cases, between 12 and 36 months old, treated as in Group A; Group C, of 28 cases younger than 12 months, received neither drug. The clinical severity scores for Group B were significantly more improved than Group A on days 4 and 5 (p less than 0.05 and p less than 0.05, respectively), and better than that of Group C on days 3, 4, and 5 (p less than 0.05, 0.005, and 0.05, respectively). No significant difference was found between Group A and C from days 1 to 5. The previous wheezy coughing episodes were significantly more frequent in Group B than in Groups A and C (p less than 0.05). Two-thirds of the quick responders to hydrocortisone and procaterol were 12 months old or older. The personal and family allergic history, serum IgE level, and total eosinophil count could not be used as parameter to predict responsiveness to the combined therapy of hydrocortisone and procaterol.


Tailored behavioral support for smoking reduction: development and pilot results of an innovative intervention.
Reduction of smoking may increase the likelihood of eventual smoking cessation among those not ready to quit. We describe the development and acceptance of a smoking-reduction intervention that integrates telephone counseling sessions with newsletters. A computer-assisted telephone interviewing program generates real-time-tailored counseling delivered by lay interviewers. Pilot participants (n = 53) were adult smokers scheduled for outpatient procedures in a health maintenance organization, randomized to intervention or a control condition (quarterly mailings). Smoking levels were measured by self-report and biochemically. Among intervention participants continuing at 3 months, all but one rated their telephone support person positively on all dimensions. Counseling calls were 'about right' in number, and newsletters were perceived as quite personal. Intervention recipients reported smoking significantly fewer mean cigarettes per day at 3 months than at baseline, and significantly fewer than control participants. Comparisons were non-significant under intent-to-treat analyses and on biochemical measures. The program was well received by outpatients who were not ready to quit smoking, and was implemented successfully by telephone staff who had no previous smoking cessation counseling experience. An ongoing trial is evaluating effectiveness, cost and relationship to eventual cessation.


The costs of conducting clinical research.
Physicians frequently receive payment for enrolling subjects onto clinical trials. Some view these payments as conflicts of interest. Others contend that these payments are necessary reimbursements for conducting clinical research. We evaluated the clinical and nonclinical hours and costs associated with conducting a mock phase III clinical research trial. We collected data from representatives of 21 clinical sites, on the numbers of hours associated with 13 activities necessary to the conduct of clinical research. The hours were based on enrolling 20 patients in a 12-month randomized placebo-controlled trial of a new chemotherapeutic agent. The outcome measures were disease progression and quality-of-life reports. These costs were evaluated for both government and pharmaceutical industry-sponsored trials. On average, 4,012 hours (range, 1,512 to 13,319 hours) were required for a government-sponsored trial, and 3,998 hours (range: 1735 to 15,699) were required for a pharmaceutical industry-sponsored trial involving 20 subjects with 17 office visits, or approximately 200 hours per subject. Thirty-two percent of the hours were devoted to nonclinical activities, such as institutional review board submission and completion of clinical reporting forms. On average, excluding overhead expenses, it cost slightly more than 6,094 dollars (range, 2,098 dollars to 19,285 dollars) per enrolled subject for an industry-sponsored trial, including 1,999 dollars devoted to nonclinical costs. Based on the results of our mock trial, the time required for nontreatment trial activities is considerable, and the associated costs are substantial.


Home and abroad: vets' role in dealing with rabies.
Manuela Herrera reports on a session at the BVA Congress which discussed the contributions that vets can make to tackling rabies, and how the profession can be at the forefront of a One Health approach to saving the lives of animals and people.


Coronavirus disease 2019 among pregnant Chinese women: case series data on the safety of vaginal birth and breastfeeding.
To assess whether vaginal secretions and breast milk of women with coronavirus disease 2019 (COVID-19) contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Single centre cohort study. Renmin Hospital of Wuhan University, Wuhan, Hubei province, China. We studied 13 SARS-CoV-2-infected pregnant women diagnosed between 31 January and 9 March 2020. We collected clinical data, vaginal secretions, stool specimens and breast milk from SARS-CoV-2-infected women during different stages of pregnancy and collected neonatal throat and anal swabs. We assessed viral presence in different biosamples. Of the 13 women with COVID-19, five were in their first trimester, three in their second trimester and five in their third trimester. Of the five women in their third trimester who gave birth, all delivered live newborns. Among these five deliveries, the primary adverse perinatal outcomes included premature delivery (n = 2) and neonatal pneumonia (n = 2). One of nine stool samples was positive; all 13 vaginal secretion samples, and five throat swabs and four anal swabs collected from neonates, were negative for the novel coronavirus. However, one of three samples of breast milk was positive by viral nucleic acid testing. In this case series of 13 pregnant women with COVID-19, we observed negative viral test results in vaginal secretion specimens, suggesting that a vaginal delivery may be a safe delivery option. However, additional research is urgently needed to examine breast milk and the potential risk for viral contamination. New evidence for the safety of vaginal delivery and breastfeeding in pregnant women infected with SARS-CoV-2, positive viral result in a breast-milk sample.


[Cryopreserved amniotic membranes use in resistant vascular ulcers].
Amniotic membranes are used with success in ophthalmology to treat corneal wounds and ulcers. In this pilot study, we attempt to assess the tolerance of amniotic membranes in the management of resistant venous and/or arterial vascular ulcers. We prospectively included 8 patients, 7 males and 1 female, mean age 69.5+/- 9.6 years, with venous and/or arterial ulcers resistant after 6 months with usual medical care and/or after revascularisation failure. Amniotic membranes were applied on a weekly basis with the fetal side on the ulcer, covered by a secondary bandage. The primary end-point was evaluation of tolerance of amniotic membranes on vascular ulcers. The secondary end-points were a >50% reduction of ulcer's area, a significant (P< or =0.05) improvement of pain visual scale score and the quality of life assessed by the SF-36 questionnaire. Tolerance was excellent in all cases. We observed no adverse effect. We observed complete healing at weeks 19 and 26 for 2 patients and a >50% reduction of ulcer area at weeks 26, 31 and 32 for 3 patients. A sixth patient had an ulcer area reduction <50% and the 2 remaining showed no improvement. A significant improvement was noticed for visual pain scale and the health feeling dimension in the SF-36 questionnaire. No adverse effect or amputation requirement was noted. These preliminary results are encouraging and require a larger confirmatory study. Further studies are required to clarify the action mode of this therapeutic option.


Performance characteristics of methods of analysis used for regulatory purposes. I. Drug dosage forms. B. Gas chromatographic methods.
Gas chromatographic methods for the analysis of drug dosage forms consist of a simple extraction, dilution with an internal standard solution, and injection, or, even simpler, dilution with the internal standard solution and injection. These methods were used in 7 collaborative studies of the determination of 12 pharmaceuticals, published in the Journal of the AOAC during 1973-1983. A total of 43 individual materials consisting of various dosage forms were each analyzed, usually in duplicate, by an average of 8 laboratories, with a total of 582 reported determinations. The average within-laboratory coefficient of variation (CVo) was 1.25% and the average among-laboratories coefficient of variation (CVx) was 2.41%, for a CVo/CVx ratio of 0.52, at an average outlier rate of 1.4% of the reported values. The line of best fit for CVx plotted against concentration increases with decreasing concentration, extending from a CVx of approximately 1.8% at 100% concentration to a CVx of approximately 3.2% at 1% concentration. The change in CVx for a 10-fold decrease in concentration is approximately 0.7% CVx, independent of analyte and matrix.


A generalized-growth model to characterize the early ascending phase of infectious disease outbreaks.
A better characterization of the early growth dynamics of an epidemic is needed to dissect the important drivers of disease transmission, refine existing transmission models, and improve disease forecasts. We introduce a 2-parameter generalized-growth model to characterize the ascending phase of an outbreak and capture epidemic profiles ranging from sub-exponential to exponential growth. We test the model against empirical outbreak data representing a variety of viral pathogens in historic and contemporary populations, and provide simulations highlighting the importance of sub-exponential growth for forecasting purposes. We applied the generalized-growth model to 20 infectious disease outbreaks representing a range of transmission routes. We uncovered epidemic profiles ranging from very slow growth (p=0.14 for the Ebola outbreak in Bomi, Liberia (2014)) to near exponential (p>0.9 for the smallpox outbreak in Khulna (1972), and the 1918 pandemic influenza in San Francisco). The foot-and-mouth disease outbreak in Uruguay displayed a profile of slower growth while the growth pattern of the HIV/AIDS epidemic in Japan was approximately linear. The West African Ebola epidemic provided a unique opportunity to explore how growth profiles vary by geography; analysis of the largest district-level outbreaks revealed substantial growth variations (mean p=0.59, range: 0.14-0.97). The districts of Margibi in Liberia and Bombali and Bo in Sierra Leone had near-exponential growth, while the districts of Bomi in Liberia and Kenema in Sierra Leone displayed near constant incidences. Our findings reveal significant variation in epidemic growth patterns across different infectious disease outbreaks and highlights that sub-exponential growth is a common phenomenon, especially for pathogens that are not airborne. Sub-exponential growth profiles may result from heterogeneity in contact structures or risk groups, reactive behavior changes, or the early onset of interventions strategies, and consideration of "deceleration parameters" may be useful to refine existing mathematical transmission models and improve disease forecasts.


Role of the renin-angiotensin system in the regulation of glomerular filtration.
Angiotensin II (Ang II) controls renal plasma flow, which depends on perfusion pressure and on renal vascular resistances; the glomerular filtration rate of single nephrons (SNGFR) also depends on these two parameters. The glomerulus can synthesize all components of the renin-angiotensin system. Renin is produced by mesangial cells and cells of afferent arterioles, angiotensinogen by mesangial cells, and angiotensin I-converting enzyme (ACE) by endothelial and mesangial cells. Ang II binds to afferent and efferent arterioles and to mesangial cells, which subsequently contract and enhance their production of vasodilator prostaglandins. Ang II participates in the regulation of the SNGFR by acting on arteriolar resistance, on the glomerular capillary surface area, and finally on the ultrafiltration coefficient. The synthesis of renin is initiated when the cAMP concentration increases under the influence of hormones (parathyroid hormone, catecholamines), of mediators (e.g., prostanoids), or of changes in composition of tubular fluid (in sodium, chlorine, or calcium) detected by the macula densa. Moreover, renin synthesis is stimulated by decreases in intracellular calcium concentration. The renin-angiotensin system plays an important role in the regulation of glomerular filtration. A decrease in renal plasma flow is followed by an increase in glomerular efferent arteriole resistance, so that perfusion pressure and glomerular filtration remain constant. Furthermore, if the decrease in renal plasma flow is more marked, vasodilator prostaglandins, whose synthesis is stimulated by Ang II, dilate afferent arterioles, which sustains glomerular filtration. Prostaglandins are also apt to bind to the juxtaglomerular apparatus and to increase the intracellular cAMP level.(ABSTRACT TRUNCATED AT 250 WORDS)


Communication: vacuum ultraviolet photoabsorption of interstellar icy thiols.
Following the recent identification of ethanethiol in the interstellar medium (ISM) we have carried out Vacuum UltraViolet (VUV) spectroscopy studies of ethanethiol (CH3CH2SH) from 10 K until sublimation in an ultrahigh vacuum chamber simulating astrochemical conditions. These results are compared with those of methanethiol (CH3SH), the lower order thiol also reported to be present in the ISM. VUV spectra recorded at higher temperature reveal conformational changes in the ice and phase transitions whilst evidence for dimer production is also presented.


Practical Guidance for Clinical Microbiology Laboratories: Mycobacteria.
Mycobacteria are the causative organisms for diseases such as tuberculosis (TB), leprosy, Buruli ulcer, and pulmonary nontuberculous mycobacterial disease, to name the most important ones. In 2015, globally, almost 10 million people developed TB, and almost half a million patients suffered from its multidrug-resistant form. In 2016, a total of 9,287 new TB cases were reported in the United States. In 2015, there were 174,608 new case of leprosy worldwide. India, Brazil, and Indonesia reported the most leprosy cases. In 2015, the World Health Organization reported 2,037 new cases of Buruli ulcer, with most cases being reported in Africa. Pulmonary nontuberculous mycobacterial disease is an emerging public health challenge. The U.S. National Institutes of Health reported an increase from 20 to 47 cases/100,000 persons (or 8.2% per year) of pulmonary nontuberculous mycobacterial disease among adults aged 65 years or older throughout the United States, with 181,037 national annual cases estimated in 2014. This review describes contemporary methods for the laboratory diagnosis of mycobacterial diseases. Furthermore, the review considers the ever-changing health care delivery system and stresses the laboratory's need to adjust and embrace molecular technologies to provide shorter turnaround times and a higher quality of care for the patients who we serve.


Postural instability and consequent falls and hip fractures associated with use of hypnotics in the elderly: a comparative review.
The aim of this review is to establish the relationship between treatment with hypnotics and the risk of postural instability and as a consequence, falls and hip fractures, in the elderly. A review of the literature was performed through a search of the MEDLINE, Ingenta and PASCAL databases from 1975 to 2005. We considered as hypnotics only those drugs approved for treating insomnia, i.e. some benzodiazepines and the more recently launched 'Z'-compounds, i.e. zopiclone, zolpidem and zaleplon. Large-scale surveys consistently report increases in the frequency of falls and hip fractures when hypnotics are used in the elderly (2-fold risk). Benzodiazepines are the major class of hypnotics involved in this context; falls and fractures in patients taking Z-compounds are less frequently reported, and in this respect, zolpidem is considered as at risk in only one study. It is important to note, however, that drug adverse effect relationships are difficult to establish with this type of epidemiological data-mining. On the other hand, data obtained in laboratory settings, where confounding factors can be eliminated, prove that benzodiazepines are the most deleterious hypnotics at least in terms of their effects on body sway. Z-compounds are considered safer, probably because of their pharmacokinetic properties as well as their selective pharmacological activities at benzodiazepine-1 (BZ(1)) receptors. The effects of hypnotics on balance, gait and equilibrium are the consequence of differential negative impacts on vigilance and cognitive functions, and are highly dose- and time-dependent. Z-compounds have short half-lives and have less cognitive and residual effects than older medications. Some practical rules need to be followed when prescribing hypnotics in order to prevent falls and hip fractures as much as possible in elderly insomniacs, whether institutionalised or not. These are: (i) establish a clear diagnosis of the sleep disorder; (ii) take into account chronic conditions leading to balance and gait difficulties (motor and cognitive status); (iii) search for concomitant prescription of psychotropics and sedatives; (iv) use half the recommended adult dosage; and (v) declare any adverse effect to pharmacovigilance centres. Comparative pharmacovigilance studies focused on the impact of hypnotics on postural stability are very much needed.


A depressant effect of acetylcholine on the idio-ventricular pacemaker of the isolated perfused rabbit heart.
In Langendorff preparations of the isolated rabbit heart, excision of the atria and severance of the atrio-ventricular bundle resulted in the onset of idio-ventricular rhythm at a rate much below the original sino-atrial rate. The mean decrease in rate in twelve experiments was 61%. Acetylcholine perfusion decreased the idio-ventricular rate still further. Physostigmine augmented this effect while atropine prevented or abolished it. Similar results were obtained with a rat heart. The results indicate that a cholinergic receptor mechanism is present at pacemaker sites in mammalian ventricles. However, when rabbit ventricles, beating under atrio-ventricular nodal rhythm or idio-ventricular rhythm, were cooled to the point of cardiac arrest, acetylcholine failed to cause reappearance of the cardiac beat.


[Combination of COVID-19 vaccines and their efficacy: a theoretical proposalCombinação de vacinas contra a COVID-19 e sua eficácia: uma proposta teórica].
In the face of the coronavirus disease 2019 (COVID-19) pandemic, the entire world is concerned with achieving desired herd immunity to overcome the current health crisis. Estimating the efficacy that could be attained in a population by combining vaccines of different brands or technologies would be a valuable asset for public health decision-makers in the present pandemic and in similar future scenarios. This article provides a mathematical formula to estimate probable efficacy against COVID-19 when administering two vaccines in a specific population. These vaccines, given in a series, could be of different technologies and brands.


Thrombospondin-1 production is enhanced by Porphyromonas gingivalis lipopolysaccharide in THP-1 cells.
Periodontitis is a chronic inflammatory disease caused by gram-negative anaerobic bacteria. Monocytes and macrophages stimulated by periodontopathic bacteria induce inflammatory mediators that cause tooth-supporting structure destruction and alveolar bone resorption. In this study, using a DNA microarray, we identified the enhanced gene expression of thrombospondin-1 (TSP-1) in human monocytic cells stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS). TSP-1 is a multifunctional extracellular matrix protein that is upregulated during the inflammatory process. Recent studies have suggested that TSP-1 is associated with rheumatoid arthritis, diabetes mellitus, and osteoclastogenesis. TSP-1 is secreted from neutrophils, monocytes, and macrophages, which mediate immune responses at inflammatory regions. However, TSP-1 expression in periodontitis and the mechanisms underlying TSP-1 expression in human monocytic cells remain unknown. Here using real-time RT-PCR, we demonstrated that TSP-1 mRNA expression level was significantly upregulated in inflamed periodontitis gingival tissues and in P. gingivalis LPS-stimulated human monocytic cell line THP-1 cells. TSP-1 was expressed via Toll-like receptor (TLR) 2 and TLR4 pathways. In P. gingivalis LPS stimulation, TSP-1 expression was dependent upon TLR2 through the activation of NF-κB signaling. Furthermore, IL-17F synergistically enhanced P. gingivalis LPS-induced TSP-1 production. These results suggest that modulation of TSP-1 expression by P. gingivalis plays an important role in the progression and chronicity of periodontitis. It may also contribute a new target molecule for periodontal therapy.


[Prolapse of ureterocele in a girl. Management to pursue].
In the case of a strangulated prolapsed ureterocele on lone kidney, the authors discussed briefly the management of this complication found solely in the feminine gender. The central point to remember is that the care giving in emergency must be of a limited nature and secondly that the patient must be explored and prepared carefully before reconstructive surgery.


In vivo evaluation of the radiosensitizing and cytotoxic properties of newly synthesized electron-affinic drugs.
We are synthesizing and testing various 2-nitroimidazole analogs with different octanol/water partition coefficients for their radiosensitizing and cytototoxic properties. Our hypothesis is that, unlike the situation in vitro, lipophilicity will play a major role in determining the extent of radiosensitization of hypoxic tumour cells in vivo and also the degree of animal toxicity. The radiosensitivity testing involves determination of the surviving fraction of EMT6 tumour cells irradiated in vivo under different conditions following drug injection, and subsequent assay in vitro. Data obtained to date on eight 2-nitroimidazoles do not indicate any compound clearly superior to misonidazole (Ro-07-0582), although one or two are close and may prove better at the completion of testing. Cytotoxicity of the compounds is assayed by cell survival and histologically. Data obtained on the toxicity of misonidazole to the cells of EMT6 tumours suggest that a large proportion of the anoxic cells in these tumours are not near necrotic areas, but rather result from the temporary closure of blood vessels.


Coordinated regulation of c-Myc and Max in rat liver development.
The processes of liver development and regeneration involve regulation of a key network of transcription factors, the c-myc/max/mad network. This network regulates the expression of genes involved in hepatocyte proliferation, growth, metabolism, and differentiation. In previous studies on the expression and localization of c-Myc in the fetal and adult liver, we made the unexpected observation that c-Myc content was similar in the two. However, c-Myc was localized predominantly to the nucleolus in the adult liver. On the basis of this finding, we went on to characterize the expression patterns of the other members of the network, max and mad, comparing their regulation during late fetal development with the proliferation of mature hepatocytes that is seen in liver regeneration. We found that Max content, rather than being constitutive, as predicted by other studies, was elevated in the fetal liver compared with the adult liver. Its content correlated with hepatocyte proliferation during the perinatal transition. In contrast, mad4 expression was decreased in the fetal liver compared with the adult liver. Nucleolar localization of c-Myc coincided with changes in Max content. To explore this relationship, we overexpressed Max in cultured adult hepatocytes. High levels of Max resulted in a shift in c-Myc localization from nucleolar to diffuse nuclear. In contrast, liver regeneration was associated with an increase in c-Myc content but no change in Max content. We conclude that the regulation of Max content during liver development and its potential role in determining c-Myc localization are means by which Max may control the biological activity of the c-Myc/Max/Mad network during liver development.


Experience with DPP-4 inhibitors in the management of patients with type 2 diabetes fasting during Ramadan.
A large proportion of Muslim patients with type 2 diabetes mellitus (T2DM) elect to fast during the holy month of Ramadan. For these patients hypo- and hyperglycemia constitute two major complications associated with the profound changes in food pattern during the Ramadan fast, and efficacious treatment options with a low risk of hypoglycemia are therefore needed to manage their T2DM as effectively and safely as possible. Dipeptidyl peptidase-4 (DPP-4) inhibitors modulate insulin and glucagon secretion in a glucose-dependent manner, and consequently a low propensity of hypoglycemia has consistently been reported across different patient populations with these agents. Promising data with DPP-4 inhibitors have now also started to emerge in patients with T2DM fasting during Ramadan. The objective of this review is to provide a comprehensive overview of the currently available evidence and potential role of DPP-4 inhibitors in the management of patients with T2DM fasting during Ramadan whose diabetes is treated with oral antidiabetic drugs, and to discuss the mechanistic basis for their beneficial effects in this setting.


A comprehensive program of cognitive stimulation with digital inclusion, physical activity and social interaction can modify BDNF levels and improve cognition in adults over 50: a randomized controlled pilot study.
To analyze the effect of a comprehensive program of cognitive stimulation with digital inclusion, physical activity and social interaction, called "Oficina da Lembrança" (OL), on the cognitive status and concentration of biomarkers of neuroplasticity, neurodegeneration in adults aged 50 years and over attending a Memory Clinic. In this pilot randomized controlled study, 64 patients without dementia aged 45 to 79 years, seen at a University Memory Clinic in Southern Brazil, were randomly allocated to the intervention and control groups. The intervention consisted of participation in OL for 12 weeks. Serum biomarkers (brain-derived neurotrophic factor [BDNF], S100β, and neuron-specific enolase [NSE]) and cognitive status were analyzed as primary and secondary outcomes. The Wilcoxon test and Generalized Estimating Equations (GEE) were applied. Of the 64 patients invited to participate in the study, 33 (intervention: 17, control: 16) completed the study with all data. Improvement of cognitive status was significant in the intervention group (22.6 to 24.5) but not in the control group (20.1 to 21.1). There was a significant reduction of BDNF in OL participants, but no significant change was observed in the neurodegenerative biomarkers S100β or NSE. The concentration of BDNF decreased significantly post-OL in the intervention group (-288.1, 95%CI -362.1 to -94.1), even after adjusting for sex, age, and educational level. Cognitive status was significantly improved in OL participants. The OL program improved cognitive status, reduced serum BDNF levels, and empowered digitally excluded older adults. There was no effect of this intervention on S100β or NSE. This study has a Universal Trial Number (UTN) U1111-1195-2642 and was registered in the Brazilian Clinical Trials Registry (ReBEC), number RBR-38X665.


[The development and features of multi-acupoints moxibustion instrument].
A new type of multi-acupoints moxibustion instrument was developed to effectively solve the issue of simultaneously performing moxibustion at multiple acupoints. The moxibustion instrument consisted of a bracket and a moxibustion cartridge mounted on the bracket. The upper end of the bracket was equipped with gooseneck tubes. The free end of the gooseneck tubes was equipped with moxibustion cartridge used for moxibustion. The moxibustion cartridge consisted of the cartridge body, the moxa needle and the ash net. This current instrument with novel and unique structure was simple and reasonable, safe and reliable, and had the advantages of convenient operation, time and labor saving, and high moxibustion efficiency, and was an innovation of moxibustion instrument.


[The formation of skin barrier and defective barrier-associated skin diseases].
Since the discovery of loss-of-function mutations in filaggrin (FLG) gene in atopic dermatitis (AD) individuals, significant attention has been paid against the skin barrier as an initial starting point of atopic march. Although FLG is a significant cornification-associated gene, skin barrier formation is a complex process mediated by an array of genes with specific functions. In this article, the mechanism of physical skin barrier formation is reviewed in detail, focusing on specific gene functions and inherited disorders caused by genetic aberrations. Additionally, the mechanism of percutaneous sensitization with environmental allergens in association with FLG-deficiency is reviewed in order to clarify the link between defective skin barrier and atopic march. Finally, updated knowledge of psoriasis pathophysiology in connection with genetic defect in skin barrier is reviewed. This article would provide a novel opportunity to understand the allergic/autoimmune disorders from the viewpoint of non-classical immune cells.