Glycemic response to wheat products: reduced response to pasta but no effect of fiber.
The blood glucose response to feeding 50-g carbohydrate portions of white and wholemeal bread and white spaghetti was studied in a group of nine diabetic subjects. Blood glucose rises after white and wholemeal bread were identical, but the response after spaghetti was markedly reduced. These results emphasize that food form rather than fiber may be important in determining the glycemic response and that pasta may be a useful source of carbohydrate in the diabetic diet.


Charge transfer dynamics and interlayer exciton formation in MoS2/VOPc mixed dimensional heterojunction.
Mixed-dimensional van der Waals heterojunctions involve interfacing materials with different dimensionalities, such as a 2D transition metal dichalcogenide and a 0D organic semiconductor. These heterojunctions have shown unique interfacial properties not found in either individual component. Here, we use femtosecond transient absorption to reveal photoinduced charge transfer and interlayer exciton formation in a mixed-dimensional type-II heterojunction between monolayer MoS2 and vanadyl phthalocyanine (VOPc). Selective excitation of the MoS2 exciton leads to hole transfer from the MoS2 valence band to VOPc highest occupied molecular orbit in ∼710 fs. On the contrary, selective photoexcitation of the VOPc layer leads to instantaneous electron transfer from its excited state to the conduction band of MoS2 in less than 100 fs. This light-initiated ultrafast separation of electrons and holes across the heterojunction interface leads to the formation of an interlayer exciton. These interlayer excitons formed across the interface lead to longer-lived charge-separated states of up to 2.5 ns, longer than in each individual layer of this heterojunction. Thus, the longer charge-separated state along with ultrafast charge transfer times provide promising results for photovoltaic and optoelectronic device applications.


Inactivation of both Rb and p53 pathways in mouse lung epithelial cell lines.
Aberrant expression of key cell cycle regulatory genes is essential for the immortalization and transformation of cells in vitro. We examined 20 mouse lung epithelial cell lines (2 nontumorigenic, 5 nonmetastatic, and 13 metastatic) for mutations or alterations in the expression of key components of the Rb pathway (pRb and p16INK4a) and the p53 pathway (p53 and p19ARF). Seven cell lines had a mutation in exons 5 to 8 of p53. p19ARF was inactivated in the remaining 13 cell lines, primarily by homozygous deletion. Rb expression was present and unaltered in all cell lines, with both phosphorylated and unphosphorylated protein forms detectable. p16INK4a transcripts were undetectable in all cell lines tested except LM1. Loss of p16INK4a expression was a result of homozygous deletion in 11 out of 20 lung cell lines and promoter-exon 1 hypermethylation in 6 out of the remaining 8 cell lines. Other related components that were examined in this study included p21WAF1 and cyclin D1. Compared to normal lung tissue, p21WAF1 expression levels were reduced or undetectable in all cell lines, which did not correlate with loss of p53 function, but did correlate with inactivation of either p53 or p19ARF. Although cyclin D1 expression was variable between cell lines, transcript levels were decreased by at least 50% in the nontumorigenic lines C10 and E10 compared to the tumorigenic cell lines. These results demonstrate mutually exclusive relationships between p53 and p19ARF and between Rb and p16INK4a, but perhaps not between cyclin D1 and p16INK4a, and further describe the nature of involvement of both pathways in mouse lung tumorigenesis.


Glutathione transferase superfamily behaves like storage proteins for dinitrosyl-diglutathionyl-iron complex in heterogeneous systems.
Electron paramagnetic resonance and kinetics experiments have been made to determine the formation, stability, and fate of the natural nitric oxide carrier, dinitrosyl-diglutathionyl-iron complex (DNDGIC), in heterogeneous systems approaching in vivo conditions. Both in human placenta and rat liver homogenates DNDGIC is formed spontaneously from GSH, S-nitroso-glutathione, and trace amounts of ferrous ions. DNDGIC is unstable in homogenates depleted of glutathione S-transferase (GST); an initial phase of rapid decomposition is followed by a slower decay, which is inversely proportional to the concentration. In the crude human placenta homogenate, GSTP1-1, which represents 90% of the cytosolic GST isoenzymes, is the preferential target for DNDGIC. It binds the complex almost stoichiometrically and stabilizes it for several hours (t1/2 = 8 h). In the presence of an excess of DNDGIC, negative cooperativity in GSTP1-1 opposes the complete loss of the usual detoxicating activity of this enzyme. In the rat liver homogenate, multiple endogenous GSTs (mainly Alpha and Mu class isoenzymes) bind the complex quantitatively and stabilize it (t1/2 = 4.5 h); negative cooperativity is also seen for these GSTs. Thus, the entire pool of cytosolic GSTs, with the exception of the Theta GST, represents a target for stoichiometric amounts of DNDGIC and may act as storage proteins for nitric oxide. These results confirm the existence of a cross-link between NO metabolism and the GST superfamily.


Osteotome-Mediated Sinus Lift without Grafting Material: A Review of Literature and a Technique Proposal.
Implant rehabilitation of the edentulous posterior maxilla may be a challenging procedure in the presence of insufficient bone volume for implant placement. Maxillary sinus augmentation with or without using grafting materials aims to provide adequate bone volume. The aim of the present study was to systematically review the existing literature on transalveolar maxillary sinus augmentation without grafting materials and to propose and describe an osteotome-mediated approach in postextraction sites in combination with platelet derivative. The systematic review showed that high implant survival rate (more than 96% after 5 years) can be achieved even without grafting the site, with a low rate of complications. Available alveolar bone height before surgery was not correlated to survival rate. In the described case report, three implants were placed in posterior maxilla after extraction of two teeth. An osteotome-mediated sinus lifting technique was performed with the use of platelet derivative (PRGF); a synthetic bone substitute was used to fill the gaps between implant and socket walls. No complications occurred, and implants were successfully in site after 1 year from prosthetic loading. The presented technique might represent a viable alternative for the treatment of edentulous posterior maxilla with atrophy of the alveolar bone though it needs to be validated by studies with a large sample size.


Surface nanostructuring via femtosecond lasers.
Periodical structures induced by pulsed lasers are a unique phenomenon when pulsed lasers irradiate on some material surfaces. These periodical structures with a subwavelength-scale period hold potential in integrated-optics and biomimetic micro-nanodevices for their direct shaping by laser pulses. However, the blurred nature of the laser-induced structuring hinders its further exploration in these application scopes. In this review, the plasmon-mediated structuring targeted on various materials, both organic and inorganic, will be discussed profoundly.


Infection of baboons ("Papio cynocephalus") with rotavirus (SA11).
A recent survey of nonhuman primate sera indicated that antibody to a rotavirus (SA11) was prevalent among a wide spectrum of animals. Both New and Old World species were found with antibody, many with surprisingly high titers (1:320). Whether or not infection per se was due to SA11 or an antigenically closely related agent could not be determined by that study; however, it is apparent from this study as well as from a survey of the literature that natural as well as experimental infection of nonhuman primates occurs. Recognizing that there is a need for an animal model for the study of viruses associated with human diarrhea, a preliminary investigation attempting to ascertain the susceptibility of the baboon (Papio cynocephalus) to a rotavirus was undertaken. Inoculation of four newborn baboons with SA11 resulted in diarrhea within 24 to 48 hours in all animals. One animal died 10 days postinoculation following severe diarrhea and dehydration. Virus was isolated as well as seen by electron microscopy in the stools of all four animals.


The Effect of Pender's Health Promotion Model in Improving the Nutritional Behavior of Overweight and Obese Women.
Changes in lifestyle and eating habits have put women at risk of obesity and overweight more than ever. This aim of this study was to investigate the effect of Pender's Health Promotion Model (HPM) to improve the nutritional behavior of overweight and obese women admitted to Fatemiyeh Hospital clinics in Hamadan, west Iran in 2015. In this quasi-experimental study, 108 eligible women were selected and randomly assigned to two groups: one experimental and one control. Data were gathered using three questionnaires: demographics, Pender's HPM constructs, and nutritional behavior. The questionnaires were filled out by both groups as pre-test and two months later. A Pender's HPM-based intervention was conducted for the experimental group. The data were analyzed by paired and independent t-tests, ANCOVA, and Spearmans' correlation coefficient in SPSS/16. The level of significance was considered to be <0.05. The mean score of nutritional behavior was 41.75±3.28 and 42.36±3.69 before the intervention and 79.09±5.27 and 49.72±9.49 after it in the experimental and control groups, respectively. The difference was significant only between before and after the intervention in the experimental group (P<0.001). Furthermore, the mean scores of the following variables were significantly different between before and after the intervention in the experimental group: nutritional behavior, perceived benefits, perceived self-efficacy, commitment to action, interpersonal and situational influences, behavior-related affect, and perceived barriers (P<0.001). The results showed that Pender's HPM-based training improved nutritional behavior and some constructs of the model. Therefore, this educative model can be used by healthcare providers to improve the nutritional and other health promoting behaviors.


[Effects of soil compactness on ginger plant senescence].
Based on the determinations of main physiological parameters of ginger plant grown in different compactness soils, this paper studied the effects of soil compactness on the senescence of ginger plant. The results showed that with the increase of soil compactness, the root activity and the leaf NRase activity, chlorophyll content and photosynthetic rate of ginger plant declined, while the leaf electrolytic leakage and MDA content increased. The activities of leaf SOD, POD and CAT decreased with increasing soil compactness at early growth stage but were in adverse at late growth stage. At vigorous growth stage, the root activity and the leaf chlorophyll content and photosynthetic rate in the soil with a compactness of 1.49 g cm(-3) were 30.9%, 19.0% and 17.9% lower, and the leaf electrolytic leakage and MDA content were 57.2% and 26.3% higher, respectively, compared with those in the soil with a compactness of 1.20 g cm(-3), which indicated that compacted soil could accelerate the senescence of ginger plant.


TreeBUGS: An R package for hierarchical multinomial-processing-tree modeling.
Multinomial processing tree (MPT) models are a class of measurement models that account for categorical data by assuming a finite number of underlying cognitive processes. Traditionally, data are aggregated across participants and analyzed under the assumption of independently and identically distributed observations. Hierarchical Bayesian extensions of MPT models explicitly account for participant heterogeneity by assuming that the individual parameters follow a continuous hierarchical distribution. We provide an accessible introduction to hierarchical MPT modeling and present the user-friendly and comprehensive R package TreeBUGS, which implements the two most important hierarchical MPT approaches for participant heterogeneity-the beta-MPT approach (Smith & Batchelder, Journal of Mathematical Psychology 54:167-183, 2010) and the latent-trait MPT approach (Klauer, Psychometrika 75:70-98, 2010). TreeBUGS reads standard MPT model files and obtains Markov-chain Monte Carlo samples that approximate the posterior distribution. The functionality and output are tailored to the specific needs of MPT modelers and provide tests for the homogeneity of items and participants, individual and group parameter estimates, fit statistics, and within- and between-subjects comparisons, as well as goodness-of-fit and summary plots. We also propose and implement novel statistical extensions to include continuous and discrete predictors (as either fixed or random effects) in the latent-trait MPT model.


Effect of culture conditions on fetal mouse pancreas in vitro and after transplantation in syngeneic and allogeneic recipients.
Organ culture of fetal mouse pancreas under conditions designed to either maximally preserve islet cell survival or reduce immunogenicity was used to test the efficacy of islet graft function in diabetic syngeneic or fully allogeneic recipients. Organ culture in either 90% O2, or at low temperature (22 degrees C), or in a combination of 90% O2 and 22 degrees C for 14 days not only failed to reduce immunogenicity in fully allogeneic recipients but also diminished endocrine cell survival in grafts in syngeneic recipients. Monitoring of in vitro insulin secretion provided a better guide to future graft function than did the insulin content of the cultured tissue. It is concluded that culture conditions that have been shown to reduce immunogenicity (high O2 concentration and low temperature) are not synergistic when used together and are also potentially damaging to endocrine cells.


Morphometric study of the lumbar vertebrae in dried anatomical collections.
The objective of this anatomical study was to perform the morphometry of dried lumbar vertebrae in human cadavers. This study utilized 200 adult human cadaveric dried lumbar vertebrae. The digital Vernier calipers was used to perform the measurements. The height, antero-posterior length, transverse length of the body of the vertebrae, interpedicular distance at the lateral ends, lamina length, height and thickness, superior and inferior articular facet height and width, mid sagittal and transverse diameter of vertebral foramen, height, width and thickness of the pars inter-articularis were measured. The vertebral body's anteroposterior length was more at the lower border than at the superior border ( p < 0.01). The length of lamina was higher over the right in comparison to the left (p < 0.001). The height of lamina, width of inferior articular facet, diameter of lateral recess and thickness of pars inter-articularis were greater for the left sided specimens ( p < 0.01). The statistical significance was not observed for the comparison of the remaining parameters ( p > 0.05). This anatomical study offered several dimensions of lumbar vertebrae, which are essential in the surgical practice. The implants at the lumbar vertebrae need to be manufactured based on the anatomical dimensions of that particular sample population.


Relevance of Iron Deposition in Deep Gray Matter Brain Structures to Cognitive and Motor Performance in Healthy Elderly Men and Women: Exploratory Findings.
Iron deposition increases in normal aging, has its greatest presence in structures of the extrapyramidal system, and may contribute to functional decline. MR imaging provides a method for indexing iron deposition in brain structures because of iron's ferromagnetic properties, which interact with the MRI environment to cause signal intensity attenuation that is quantifiable by comparing images collected at 1.5 and 3.0 T. We tested functional correlates of an MR-based iron index in 10 healthy, elderly individuals previously reported to have a higher iron burden in the putamen and lower in the thalamus than young individuals. Lower scores on the Dementia Rating Scale and longer reaction times on a two-choice attention test correlated with higher iron estimates in the caudate nucleus and putamen; poorer Mini-Mental State Examination and Digit Symbol scores correlated with lower iron estimates in the thalamus. Further analyses based on multiple regression, which considered regional FDRI estimates and volume measures as predictors of performance, identified iron but not the sampled volume as the unique predictor in each case. These exploratory correlations suggest a substrate of performance degradation in aging and have implications for regional signal darkening in an array of MR-based imaging protocols.


Early metazoan development: the origin of the Cambrian exuberance.
A number of common features can be observed in the earliest developing embryos of all animal phyla. A simple extant model of morphogenesis is outlined here, with the aim of giving a model of the relatively rapid appearance of Cambrian animals, 541-515 mya. Developmental patterning, elucidated by a simple linear model with only short-range diffusion of ligands, is given as the origin of the most primitive animals. The key aspect of the model involves the interaction between the emergence of the Wnt and Hedgehog (Hh) signaling pathways. The non-canonical Wnt pathway is crucial in first establishing a sphere of cells, by way of cell-cell connection fi bers. A mutation in the Wnt pathway at the dawn of multicellular organisms is argued to have given rise to the early Hh pathway, and their interaction gives two spatially separate gene determination regions, the key goal of biological patterning.


Stability-indicating high-performance thin-layer chromatographic method for analysis of itraconazole in bulk drug and in pharmaceutical dosage form.
A new, simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic method has been established for analysis of itraconazole (ITZ) in the bulk drug and in pharmaceutical formulations. Separation was achieved on aluminium plate precoated with silica gel 60F254 using Toluene : Chloroform : Methanol [5: 5: 1.5(v/v)] as mobile phase. Densitometric analysis was performed at 260 nm. Compact bands of ITZ were obtained at Rf 0.52 ± 0.02. Linearity (R(2) = 0.9978), limit of detection (180.29 ng/band), limit of quantification (546.34 ng/band), recovery (98-102%), and precision (≤0.51%) were satisfactory. Drug was not degraded under neutral and alkaline hydrolysis, UV and photolytic degradation, under-elevated temperature, and humidity. ITZ is degraded under acidic hydrolysis and oxidative condition; the degraded products were well resolved from individual bulk drug response. Developed method can effectively resolve drug from its excipients in capsule dosage form. The specificity of the method was confirmed by peak purity of resolved peak. The method can be applicable for routine analysis of ITZ in pharmaceutical formulation as stability-indicating. Because the method can effectively separate the drug from its degradation products as well as excipients, it can be used as a stability-indicating method.


[Practical knowledge in nursing training].
The study, carried through with nurses at the University Hospital Pedro Ernesto, looked to reflect on practical knowledge in the formation of the nurse. In the construction of the theoretical referential, the contributions of Patricia Benner, Phillipe Perrenoud and Donald Shön have been very relevant. From a methodological point of view, it consisted of a case study, with a qualitative approach; from semi-structured interviews with nurses involved in assisting the patient. The findings demonstrate that the competences that support the professional exercise are built on practical knowledge, theoretical knowledge, life experience, and professional socialization.


An audit of upper gastrointestinal endoscopy performed on patients at Prince Mshiyeni Memorial Hospital in Durban, KwaZulu-Natal.
Resource constraints have resulted in upper gastrointestinal endoscopy (UGE) being deferred where possible. However, delayed investigation is costly and leads to disease progression. This study audits the UGE done at a single institution. It was motivated by the observation that public hospitals often experience an acute shortage of endoscopes, which are prone to frequent breaks and service delivery is further compromised by an increased workload. This was a retrospective observational descriptive study of patients aged 20 to 45 years who had undergone gastrointestinal endoscopy (UGE) at Prince Mshiyeni Memorial Hospital (PMMH) in KwaZulu-Natal, during the period January 2015 to December 2015. One hundred and ninety-four patients' charts and UGE reports were reviewed. Data were analysed using SPSS Statistics version 24. The level of significance was set at p < 0.05. Variables were expressed as mean ± standard deviation or medians (interquartile range IQR) as appropriate. Mean ± standard deviation was compared using the Student's t-test. Proportions and categorical variables were compared using the Pearson's chi-square test or Fisher's exact test as appropriate. An ethical approval was obtained from the University of KwaZulu-Natal BREC (BE 447/17) and the KwaZulu-Natal Department of Health Ethics Committee. Epigastric pain was found to be the most common indication for UGE, with a total of 112 (57.7%) out of total of 194 patients, followed by upper gastrointestinal bleeding (UGIB) (42) (21.6%). Amongst patients presenting with epigastric pain, only 12(10.7%) patients could be confirmed that they had received acid suppression therapy prior to the testing. In the age group 20-25 years, there was a highest number of patients presenting with corrosive substance ingestion, 11 (25.0%). The commonest finding was gastritis in 99 patients (51.0%), followed by normal findings in 50 (25.7%) patients. Epigastric pain was the most common indication and gastritis was the predominant finding.


Critical review of clinical trials of bone marrow stem cells in liver disease.
Morbidity and mortality from cirrhosis is increasing rapidly in the Western world. Currently the only effective treatment is liver transplantation, an increasingly limited and expensive resource. Consequently, there has been great hope that stem cells may offer new therapeutic approaches in the management of liver disease. In this review we critically appraise the 11 published clinical studies of bone marrow stem cells in liver disease, and focus on the unresolved issues regarding their role. We outline the different mechanisms by which stem cells may impact on liver disease, as well as highlight the importance of the type of stem cell chosen. There are multiple different stem cell populations that have, in rodent studies, been shown to have differing effects on liver regeneration and fibrogenesis/degradation. Thus, choice of cell should reflect the desired or expected mechanism of action. The importance, and methods, of studying the fate of stem cells infused in clinical studies is emphasized as we seek to translate observations in rodents into the clinical setting. Finally, we discuss which cohorts of patients with liver disease would benefit from stem cell therapy, as well as establish minimum criteria for future clinical trials of stem cells.


"It's been quite a challenge": redesigning end-of-life care in acute hospitals.
This paper reports the findings of an interview-based study undertaken to investigate the introduction of end-of-life (EoL) care pathways in three acute trusts, as part of a larger project examining service redesign. The aim was to examine the barriers to and facilitators of change. Twenty-one in-depth qualitative interviews were conducted with staff working in three National Health Service (NHS) acute hospital trusts. These staff members were involved in end-of-life care, and their accounts were analyzed to identify the key issues when introducing service changes in these settings. Thematic analysis revealed five major themes-two of which, leadership and facilitation, and education and training, indicate what needs to be in place if end-of-life care pathways are to be adopted by staff. However, the remaining three themes of difficult conversations, diagnosing dying, and communication across boundaries highlight particular areas of practice and organization that need to be addressed before end-of-life care in hospitals can be improved. Organization of end-of-life care in acute hospitals is challenging, and care pathways provide a degree of guidance as to how services can be delivered. However, even when there is effective leadership at all levels of an organization and an extensive program of education for all staff support the use of care pathways, significant barriers to their introduction remain. These include staff anxieties concerning diagnosing dying and discussing dying and end-of-life care planning with patients and their families. It is hoped these findings can inform the development of the proposed new care plans which are set to replace end of life care pathways in England.


[Calcium permeability of synaptosomes induced by alpha-latrotoxin].
The paper deals with characteristics of ionic alpha-latrotoxin-induced permeability of rat brain synaptosomes. It has been shown that the addition of alpha-latrotoxin to synaptosomes in the Ca2+-containing media resulted in an extensive and rapid uptake of 45Ca2+ in synaptosomes. alpha -Latrotoxin was not able to enhance the 22Na+ and 86Rb+ uptake or efflux in the Ca2+-containing and Ca2+- and Mg2+-free media. The dye di-O-C3 was used to monitor the membrane potential changes as a consequence of alpha-latrotoxin treatment of synaptosomes. It has been found that alpha-latrotoxin increased synaptosomal fluorescence in the Ca2+-containing media, but failed to induce any increase of fluorescence in Ca2+- and Mg2+-free media. It has been also shown that the calcium uptake induced by alpha-latrotoxin depends on free calcium concentration in synaptosomes. Toxin-induced calcium flows are shown to be of the vector character.


[A study on a model for internet addiction of adolescents].
This study was to identify the effects of the predictive factors of Internet addiction and to develop a predictive model that explains Internet addiction among adolescents in Korea. Data was collected from 664 adolescents in Puasan and Ulsan. Data analysis was done using the SPSS 10.0 Win Program for descriptive and correlational statistics and the LISREL 8.53 Win Program for Covariance structural analysis. The fit of the hypothetical model to the data was moderate, it was modified by deleting four paths. Compared to the hypothetical model, the revised one had a better fit to the data(chi2/df=6.50, GFI=.99, AGFI=.90, RMR=.02, NNFI=.88, NFI=.98, CN=279). Gender, friend support, and loneliness had significant direct effects on Internet addiction. The direct and indirect effect of self-esteem on Internet addiction was significant. The indirect effect of family support on Internet addiction was significant but its direct effect was insignificant. The direct and indirect effects of stress and impulsiveness on Internet addiction were significant but their total effects were insignificant. Finally, to decrease loneliness, and to increase family support and self-esteem, an effective intervention program and education should be developed to prevent Internet addiction of adolescents.


Heavy Thermal Dark Matter from a New Collision Mechanism.
We propose a new thermal freeze-out mechanism that results in dark matter masses exceeding the unitarity bound by many orders of magnitude, without violating perturbative unitarity or modifying the standard cosmology. The process determining the relic abundance is χζ^{†}→ζζ, where χ is the dark matter candidate. For m_{ζ}<m_{χ}<3m_{ζ}, χ is cosmologically long-lived and scatters against the exponentially more abundant ζ. Therefore, such a process allows for exponentially heavier dark matter for the same interaction strength as a particle undergoing ordinary 2→2 freeze-out, or equivalently, exponentially weaker interactions for the same mass. We demonstrate this mechanism in a leptophilic dark matter model, which allows for dark matter masses up to 10^{9} GeV.


Histological considerations in implant patients.
The selection of patients for cochlear implantation requires consideration of a variety of anatomical and histological facts. Mechanical impediments to cochlear implantation, including the consequences of chronic otitis media, bony obliteration of the membranous labyrinth, or labyrinthitis ossificans, following bacterial labyrinthitis or vascular compromise of the inner ear, obliterative otosclerosis, and middle-ear dysplasias may present difficulties in access to the inner ear and placement of electrodes. Consideration of the histopathological features of known causes of profound deafness will help predict the presence or absence of inner ear structures essential for successful implantation. The identity of these critical structures and the histopathologic characteristics of bacterial labyrinthitis, fungal meningitis, syphilis of the inner ear, otosclerosis, presbycusis, genetically determined degenerations, trauma, intoxications, inflammatory, autoimmune and idiopathic disorders are presented in terms of their relevance for cochlear implantation.


Suicide risk during the lockdown due to coronavirus disease (COVID-19) in Colombia.
The study aimed to estimate the high suicide risk during the COVID-19 lockdown in the Colombian population. A total of 700 adults aged between 18 and 76 years (M = 37.1, SD = 12.7; 68.0% women) completed an online questionnaire. Findings showed that 7.6% of participants reported a high suicide risk. High suicide risk was associated with high perceived stress related to COVID-19, risk of depressive episode, and insomnia. Our study suggests that 1 out of 13 Colombians in a non-probability sample reports a high suicide risk during COVID-19. Findings need to be corroborated in a representative sample of Colombians.


Glutamate carboxypeptidase II inhibition behaviorally and physiologically improves pyridoxine-induced neuropathy in rats.
Pyridoxine is used as a supplement for treating conditions such as vitamin deficiency as well as neurological disorders such as depression, epilepsy and autism. A significant neurologic complication of pyridoxine therapy is peripheral neuropathy thought to be a result of long-term and high dose usage. Although pyridoxine-induced neuropathy is transient and can remit after its withdrawal, the process of complete recovery can be slow. Glutamate carboxypeptidase II (GCP II) inhibition has been shown to improve symptoms of both chemotherapy- and diabetic-induced neuropathy. This study evaluated if GCP II inhibition could behaviorally and physiologically improve pyridoxine-induced neuropathy. In the current study, high doses of pyridoxine (400 mg/kg, twice a day for seven days) were used to induce neuropathy in rats. An orally bioavailable GCP II inhibitor, 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA), was administered daily at a dose of 30 mg/kg starting from the onset of pyridoxine injections. Body weight, motor coordination, heat sensitivity, electromyographical (EMG) parameters and nerve morphological features were monitored. The results show beneficial effects of GCP II inhibition including normalization of hot plate reaction time, foot fault improvements and increased open field distance travelled. H wave frequency, amplitude and latency as well as sensory nerve conduction velocity (SNCV) were also significantly improved by 2-MPPA. Lastly, GCP II inhibition resulted in morphological protection in the spinal cord and sensory fibers in the lumbar region dorsal root ganglia (DRG). In conclusion, inhibition of GCP II may be beneficial against the peripheral sensory neuropathy caused by pyridoxine.


Aberrant expression and distribution of enzymes of the urea cycle and other ammonia metabolizing pathways in dogs with congenital portosystemic shunts.
The detoxification of ammonia occurs mainly through conversion of ammonia to urea in the liver via the urea cycle and glutamine synthesis. Congenital portosystemic shunts (CPSS) in dogs cause hyperammonemia eventually leading to hepatic encephalopathy. In this study, the gene expression of urea cycle enzymes (carbamoylphosphate synthetase (CPS1), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase (ARG1)), N-acetylglutamate synthase (NAGS), Glutamate dehydrogenase (GLUD1), and glutamate-ammonia ligase (GLUL) was evaluated in dogs with CPSS before and after surgical closure of the shunt. Additionally, immunohistochemistry was performed on urea cycle enzymes and GLUL on liver samples of healthy dogs and dogs with CPSS to investigate a possible zonal distribution of these enzymes within the liver lobule and to investigate possible differences in distribution in dogs with CPSS compared to healthy dogs. Furthermore, the effect of increasing ammonia concentrations on the expression of the urea cycle enzymes was investigated in primary hepatocytes in vitro. Gene-expression of CPS1, OTC, ASL, GLUD1 and NAGS was down regulated in dogs with CPSS and did not normalize after surgical closure of the shunt. In all dogs GLUL distribution was localized pericentrally. CPS1, OTC and ASS1 were localized periportally in healthy dogs, whereas in CPSS dogs, these enzymes lacked a clear zonal distribution. In primary hepatocytes higher ammonia concentrations induced mRNA levels of CPS1. We hypothesize that the reduction in expression of urea cycle enzymes, NAGS and GLUD1 as well as the alterations in zonal distribution in dogs with CPSS may be caused by a developmental arrest of these enzymes during the embryonic or early postnatal phase.


Reduced morbidity and mortality rates of the heparin-induced thrombocytopenia syndrome.
We reported a 61% morbidity rate and a 23% mortality rate for the heparin-induced thrombocytopenia (HIT) syndrome in 1983. We subsequently reported in 1987 that with early recognition, immediate cessation of the administration of heparin, and platelet function inhibition, the morbidity rate could be reduced to 23% and the mortality rate to 12%. One hundred recent cases of patients with heparin-associated antiplatelet antibodies (HAAb) have been reviewed to determine whether aggressive screening, early diagnosis, and alternate management could further reduce morbidity and mortality rates. The consecutive records of 100 patients with positive platelet aggregation tests were reviewed. Sixty-six patients were male. The patients' ages ranged from 23 days to 92 years. The patients were from vascular (28), cardiothoracic (42), and other (30) services. HIT was suspected in patients who received heparin and had falling platelet counts, platelet counts less than 100,000/mm3, or new thromboembolic or hemorrhagic events. Heparin was not offered to six patients with known HAAb. Twelve patients were successfully treated with antiplatelet therapy and limited reexposure to heparin, and 75 patients were successfully treated with early diagnosis and prompt cessation of heparin. Alternate forms of anticoagulation therapy were used selectively. Seven patients had 11 complications. Three of the seven patients were treated successfully with warfarin anticoagulation and aspirin (2) or with aspirin alone (1). A fourth patient was treated with thrombectomy, hematoma evacuation, and aspirin. A fifth patient underwent thrombolysis and coronary angioplasty in addition to receiving warfarin and aspirin. The sixth patient required two thrombectomies and warfarin. A seventh patient required two thrombectomies and aspirin. HIT was responsible for one of 17 deaths. A 7.4% morbidity rate and a 1.1% mortality rate have been achieved in patients with HAAb by aggressive screening, early recognition of HIT, and prompt cessation of the administration of heparin. Platelet function inhibitors and other anticoagulants, including nonreacting low molecular weight heparin, are important adjuncts in the management of the thromboembolic disorders associated with HIT.


[On the mode of action of antirheumatic drugs (author's transl)].
Since the etiology of rheumatoid arthritis presently is mostly unknown, the therapeutical efforts are focussed on attempts to influence the pathogeneic events occurring in this disease. Among the discussed pathogenic mechanisms aberration of immunereactions seem to play an important role. The drugs mainly used for basical treatment of rheumatoid arthritis are cytostatics, D-penicillamine, gold salts and chloroquine. The clinical experiences with these drugs and their mode of action are reviewed.


Infantile fibrosarcoma with an EGFR kinase domain duplication: Underlining a close relationship with congenital mesoblastic nephroma and highlighting a similar morphological spectrum.
Infantile fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) are locally aggressive tumors primarily occurring in infants. Both IFS and the cellular subtype of CMN show overlapping morphological features and an ETV6-NTRK3 fusion, suggesting a close relationship. An activating alteration of EGFR, based on an EGFR kinase domain duplication (KDD), occurs in a subset of CMNs lacking an NTRK3 rearrangement, especially in the classic and mixed type. So far no EGFR-KDDs have been detected in IFS. We describe four pediatric tumors at the extremities (leg, n = 2; foot and arm n = 1) with histological features of IFS/CMN. Two cases showed classic IFS morphology while two were similar to classic/mixed type CMN. In all cases, an EGFR-KDD was identified without detection of a fusion gene. There were no abnormalities of the kidneys in any of the patients. This is the first description of IFS with an EGFR-KDD as driver mutation, supporting that IFS and CMN are similar lesions with the same morphological and genetic spectrum. Pathologists should be aware of the more fibrous variant of IFS, similar to classic/mixed type CMN. Molecular analyses are crucial to treat these lesions adequately, especially with regard to the administration of tyrosine kinase inhibitors.


Cyclooxygenase-2 expression does not correlate with outcome in osteosarcoma or rhabdomyosarcoma.
To determine if expression of cyclooxygenase (COX)-2, an inducible enzyme with known tumor-promoting activity, correlates with outcome in pediatric sarcomas. COX-2 overexpression correlates with more aggressive disease in a variety of adult solid tumors. Archived human osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma tumors were retrospectively evaluated, blinded to outcome, for COX-2 expression by immunohistochemistry and correlated with patient characteristics and survival. COX-2 expression was detected in 94 of 142 (66%) tumors (osteosarcoma, 66/99 [67%]; rhabdomyosarcoma, 21/35 [60%]; Ewing sarcoma, 7/8 [88%]) and 51 of 85 (60%) diagnostic biopsies (osteosarcoma, 26/45 [58%]; rhabdomyosarcoma, 21/35 [60%]; Ewing sarcoma, 4/5 [80%]). COX-2 expression did not vary with clinicopathologic features and was not predictive of prognosis in these cases. This study does not support the use of COX-2 expression as an upfront prognostic variable in patients with osteosarcoma or rhabdomyosarcoma. Results from the small number of patients studied with Ewing sarcoma suggest a similar lack of predictive value for COX-2 expression. However, COX-2 inhibitors are not entirely dependent upon enzyme expression for their antitumor effects; this study does not necessarily preclude the use of COX-2 inhibitors for the treatment of pediatric sarcomas.


Histochemical evaluation of the coagulation depth after argon laser impact on a port-wine stain.
A two-step excisional treatment of a port-wine stain (PWS) on the back of a 43-yr-old female patient was performed. Immediately before the first surgical treatment, two corresponding series of argon laser impacts were performed, each on one PWS half. Different laser parameters with irradiances ranging from 95 to 382 W/cm2 and energy fluences ranging from 19 to 114,6 J/cm2 were used. Laser spots on the first part ot be excised were biopsied 10 min after laser treatment and prepared for histochemical analysis by staining with nitro blue tetrazolium chloride (NBTC). Reduction of this redox dye by nicotinamide adenine dinucleotide diaphorase (NADH-diaphorase) leads on frozen tissue sections to an intense blue precipitate. The activity of NADH-diaphorase subsides immediately upon cell damage. All vital epidermal and dermal cells presented a dense blue granular pigment in their cytoplasm, sparing the nuclei. Laser induced arc-shaped epidermal and dermal necrosis did not stain, showing a clear demarcation from surrounding vital tissue. The depth of the thermal injury ranged from 0.28 to 0.45 mm; it did not correlate with the chosen fluences. With these penetration depths, the vast majority of PWS vessels was affected. Assessment of the remaining part of the PWS 8 months later yielded blanching of all laser-treated areas. With the NBTC method, an accurate definition of laser-induced tissue damage is feasible. It could be shown that the exposure time is the most relevant parameter influencing the penetration depth.


Identification of Receptor Binding to the Biomolecular Corona of Nanoparticles.
Biomolecules adsorbed on nanoparticles are known to confer a biological identity to nanoparticles, mediating the interactions with cells and biological barriers. However, how these molecules are presented on the particle surface in biological milieu remains unclear. The central aim of this study is to identify key protein recognition motifs and link them to specific cell-receptor interactions. Here, we employed an immuno-mapping technique to quantify epitope presentations of two major proteins in the serum corona, low-density lipoprotein and immunoglobulin G. Combining with a purpose-built receptor expression system, we show that both proteins present functional motifs to allow simultaneous recognition by low-density lipoprotein receptor and Fc-gamma receptor I of the corona. Our results suggest that the "labeling" of nanoparticles by biomolecular adsorption processes allows for multiple pathways in biological processes in which they may be "mistaken" for endogenous objects, such as lipoproteins, and exogenous ones, such as viral infections.


Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering.
Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer β-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation.


Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong.
Coronavirus disease (COVID-19) has rapidly emerged as a global health threat. The purpose of this article is to share our local experience of stepping up infection control measures in ophthalmology to minimise COVID-19 infection of both healthcare workers and patients. Infection control measures implemented in our ophthalmology clinic are discussed. The measures are based on detailed risk assessment by both local ophthalmologists and infection control experts. A three-level hierarchy of control measures was adopted. First, for administrative control, in order to lower patient attendance, text messages with an enquiry phone number were sent to patients to reschedule appointments or arrange drug refill. In order to minimise cross-infection of COVID-19, a triage system was set up to identify patients with fever, respiratory symptoms, acute conjunctivitis or recent travel to outbreak areas and to encourage these individuals to postpone their appointments for at least 14 days. Micro-aerosol generating procedures, such as non-contact tonometry and operations under general anaesthesia were avoided. Nasal endoscopy was avoided as it may provoke sneezing and cause generation of droplets. All elective clinical services were suspended. Infection control training was provided to all clinical staff. Second, for environmental control, to reduce droplet transmission of COVID-19, installation of protective shields on slit lamps, frequent disinfection of equipment, and provision of eye protection to staff were implemented. All staff were advised to measure their own body temperatures before work and promptly report any symptoms of upper respiratory tract infection, vomiting or diarrhoea. Third, universal masking, hand hygiene, and appropriate use of personal protective equipment (PPE) were promoted. We hope our initial experience in stepping up infection control measures for COVID-19 infection in ophthalmology can help ophthalmologists globally to prepare for the potential community outbreak or pandemic. In order to minimise transmission of COVID-19, ophthalmologists should work closely with local infection control teams to implement infection control measures that are appropriate for their own clinical settings.


Spatial modeling for groundwater arsenic levels in North Carolina.
To examine environmental and geologic determinants of arsenic in groundwater, detailed geologic data were integrated with well water arsenic concentration data and well construction data for 471 private wells in Orange County, NC, via a geographic information system. For the statistical analysis, the geologic units were simplified into four generalized categories based on rock type and interpreted mode of deposition/emplacement. The geologic transitions from rocks of a primary pyroclastic origin to rocks of volcaniclastic sedimentary origin were designated as polylines. The data were fitted to a left-censored regression model to identify key determinants of arsenic levels in groundwater. A Bayesian spatial random effects model was then developed to capture any spatial patterns in groundwater arsenic residuals into model estimation. Statistical model results indicate (1) wells close to a transition zone or fault are more likely to contain detectible arsenic; (2) welded tuffs and hydrothermal quartz bodies are associated with relatively higher groundwater arsenic concentrations and even higher for those proximal to a pluton; and (3) wells of greater depth are more likely to contain elevated arsenic. This modeling effort informs policy intervention by creating three-dimensional maps of predicted arsenic levels in groundwater for any location and depth in the area.


Unmet Supportive Cancer Care Needs: An Exploratory Quantitative Study in Rural Australia.
There is a discernible, often ignored under-evaluated care-management gap in supportive cancer care, where the estimated clinical outcome is seldom translated into patient-centered benefit. The present research is an exploratory cross-sectional quantitative questionnaire survey study done in rural regions of Australia with the sole purpose of evaluating the care-management gap in terms of the unmet supportive needs of advanced cancer patients to provide baseline data for planning, drafting and implementing innovative and effective supportive care services that will address the specific priorities and unmet needs identified in this vulnerable population in the remote and rural regions. The questionnaire (NA-ACP) was comprised of 132 questions covering seven domains of supportive care. Three centers in rural regions of Australia were selected for the study. While center 1 had medical and surgical specialties, centers 2 and 3 were outreach oncology clinics with nurse-led chemotherapy units. A total sample of 75 patients getting continuous treatment procedures at these three oncology units was given the NA-ACP questionnaire. The data from this study can be used to improve and inform care for this population by identifying specific unmet supportive needs.


Leiomyoma of the hand mimicking a pearl ganglion.
Leiomyomas rarely occur in the hand. To our knowledge, there have been no reports of a leiomyoma of the hand mimicking a pearl ganglion in the English literature. We report such a case with a leiomyoma of the right third finger in a 59-year-old woman. The tumor was excised together with the underlying sheet of tissue. The pathology revealed that the tumor was linked to the underlying structure of a vascular wall by a stalk of tumor tissue. This report serves to remind clinicians to include leiomyoma in the differential diagnosis when encountering a 'ganglion-like lesion'. Also, this report demonstrates the link between a leiomyoma and its underlying origin.


Landing adaptations following isolated lateral meniscectomy in athletes.
Objective functional outcomes following isolated radial lateral meniscus tears in the athlete between the ages of 14-25 are not clearly defined. The objective of this study was to determine whether patients following lateral meniscectomy demonstrate lower extremity asymmetries relative to control athletes 3 months after surgery. We hypothesized that following lateral meniscectomy, athletes aged 14-25 years old would demonstrate altered landing biomechanics compared to sex, age, height, weight, and sport-matched controls. A total of 18 subjects were included in this study. Nine patients (7 men and 2 women, 20.1 ± 2.8 years) who had undergone first-time isolated radial lateral meniscus tears were tested 3 months following partial lateral meniscectomies and compared to nine sex, age, height, weight, and sport-matched controls (7 men and 2 women, 19.7 ± 3.1 years). A ten-camera motion analysis system and two force platforms were used to collect three trials of bilateral drop landings. A 2X2 ANOVA was used to test the interaction between side (involved vs. uninvolved) and group (patient vs. control). The patient group landed with a decreased internal knee extensor moment compared to the uninvolved side and controls (interaction P < 0.05). The involved limb quadriceps isokinetic torque was not decreased compared to the contralateral or control (n.s.). Decreased knee extensor moments were significantly associated with reduced measures of function (IKDC scores: r = 0.69; P < 0.05). Athletes who return to sport at approximately 3 months following a partial lateral meniscectomy may employ compensation strategies during landing as evidenced by reduced quadriceps recruitment and functional outcome scores. Clinicians should focus on improving quadriceps function during landing on the involved leg in an attempt to decrease residual limb asymmetries. Case-control study, Level III.


The efficacy of extracorporeal shockwave lithotripsy for symptomatic ureteral stones: Predictors of treatment failure without the assistance of computed tomography.
Non-contrast computed tomography (NCCT) is not always performed clinically if the diagnosis of ureteral calculi has been confirmed using other radiographic imaging modalities. The aim of this study was to identify predictors of successful extracorporeal shockwave lithotripsy (ESWL) without assistance of NCCT. We retrospectively reviewed the medical records of patients with symptomatic solitary ureteral stones who underwent ESWL between November 2015 and January 2016. Abdominal plain radiography or intravenous urography were performed before ESWL for localization. The exclusion criteria were repeated sessions of ESWL for the target stone and congenital genitourinary tract anomalies. The demographic characteristics, clinical history, medical charges, or imaging features of the stones were recorded. Successful treatment was defined as no fragments detected on radiography or ultrasonography in 4 weeks. For radiolucent calculi, successful treatment was regarded as cases without hydronephrosis, symptoms, or hematuria. Patients experiencing intractable pain and undergoing subsequent auxiliary surgeries were regarded as having ESWL treatment failure. Age (odds ratio [OR], 1.042; 95% confidence interval [CI], 1.007-1.078), history of ipsilateral renal or ureteral calculi episodes (OR, 2.669; 95% CI, 1.281-5.687), stone burden (OR, 3.499; 95% CI, 1.284-9.530), and radiopaque stone (OR, 2.351; 95% CI, 1.049-5.267) were significant predictors of ESWL failure in all patients. For treating symptomatic ureteral stones, those with smaller size, radiolucency, and without a history of ipsilateral renal or ureteral calculi could be considered for first-line therapy with ESWL.


[A case of recurrent meningitis with association of human herpes virus-6 hepatitis].
A 27-year-old man presenting with recurrent meningitis associated with the activation of hepatitis was reported. Although he showed headache only, he was diagnosed as viral meningitis with high transaminase activities on admission. Human herpes virus-6 (HHV-6) DNA was revealed in the liver tissue by the polymerase chain reaction. This case was considered viral meningitis with HHV-6 associated hepatitis. It is suggested that the importance of viral evaluations not only herpes virus type 1 x 2, cytomegaro virus and EB virus, but also HHV-6 infection in a case of recurrent meningitis with hepatitis simultaneously.


Targeting Conserved Pathways in 3D Spheroid Formation of Diverse Cell Types for Translational Application: Enhanced Functional and Antioxidant Capacity.
Three-dimensional (3D) in vitro spheroid/organoid culture increasingly appears to better mimic physiological states than standard 2D systems. The biological consequence of 3D spheroids, however, differs for different cell types: for pluripotent embryonic stem cells (ESCs), differentiation and loss of stemness occur, while the converse is true for somatic and cancer cells. Despite such diverse consequences, there are likely conserved mechanisms governing 3D spheroid formation across cell types that are unknown but could be efficiently targeted for translational application. To elucidate such processes, we performed transcriptome analysis with functional validation on 2D- and 3D-cultured mouse ESCs, mesenchymal stromal/stem cells (MSCs), and cancer cells. At both the transcriptomic and functional levels, 3D spheroid formation resulted in commitment towards known cell-specific functional outcomes. Surprisingly in all cell types, downregulation of the cholesterol synthesis pathway was found during 3D spheroid formation, with modulation concomitantly affecting 3D spheroid formation and cell-specific consequences; similar results were seen with human cell types. Furthermore, improved antioxidant capacity after 3D spheroid formation across cell types was further enhanced with modulation of the pathway. These findings demonstrate the profound cell-specific consequences and the translational value of understanding conserved mechanisms across diverse cell types after 3D spheroid formation.


Complex excitation dynamics underlie polymorphic ventricular tachycardia in a transgenic rabbit model of long QT syndrome type 1.
Long QT syndrome type 1 (LQT1) is a congenital disease arising from a loss of function in the slowly activating delayed potassium current IKs, which causes early afterdepolarizations (EADs) and polymorphic ventricular tachycardia (pVT). The purpose of this study was to investigate the mechanisms underlying pVT using a transgenic rabbit model of LQT1. Hearts were perfused retrogradely, and action potentials were recorded using a voltage-sensitive dye and CMOS cameras. Bolus injection of isoproterenol (140 nM) induced pVT initiated by focal excitations from the right ventricle (RV; n = 16 of 18 pVTs). After the pVT was initiated, complex focal excitations occurred in both the RV and the left ventricle, which caused oscillations of the QRS complexes on ECG, consistent with the recent proposal of multiple shifting foci caused by EAD chaos. Moreover, the action potential upstroke in pVT showed a bimodal distribution, demonstrating the coexistence of 2 types of excitation that interacted to produce complex pVT: Na(+) current (INa)-mediated fast conduction and L-type Ca(2+) current (ICa)-mediated slow conduction coexist, manifesting as pVT. Addition of 2 μM tetrodotoxin to reduce INa converted pVT into monomorphic VT. Reducing late INa in computer simulation converted pVT into a single dominant reentry, agreeing with experimental results. Our study demonstrates that pVT in LQT1 rabbits is initiated by focal excitations from the RV and is maintained by multiple shifting foci in both ventricles. Moreover, wave conduction in pVT exhibits bi-excitability, that is, fast wavefronts driven by INa and slow wavefronts driven by ICa co-exist during pVT.


The common oncogenomic program of NOTCH1 and NOTCH3 signaling in T-cell acute lymphoblastic leukemia.
Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL), in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells. ChIP-seq studies show a high concordance of functional NOTCH1 and NOTCH3 genomic binding sites that are enriched in binding motifs for RBPJ, the transcription factor that recruits activated Notch to DNA. The interchangeability of NOTCH1 and NOTCH3 was confirmed by rescue of NOTCH1-dependent T-ALL cells with activated NOTCH3 and vice versa. Despite remarkable overall similarity, there are nuanced differences in chromatin landscapes near critical common Notch target genes, most notably at a Notch-dependent enhancer that regulates MYC, which correlates with responsiveness to Notch pathway inhibitors. Overall, a common oncogenomic program driven by binding of either Notch is sufficient to maintain T-ALL cell growth, whereas cell-context specific differences appear to influence the response of T-ALL cells to Notch inhibition.


Integrated Nanophotonic Waveguide-Based Devices for IR and Raman Gas Spectroscopy.
On-chip devices for absorption spectroscopy and Raman spectroscopy have been developing rapidly in the last few years, triggered by the growing availability of compact and affordable tunable lasers, detectors, and on-chip spectrometers. Material processing that is compatible with mass production has been proven to be capable of long low-loss waveguides of sophisticated designs, which are indispensable for high-light-analyte interactions. Sensitivity and selectivity have been further improved by the development of sorbent cladding. In this review, we discuss the latest advances and challenges in the field of waveguide-enhanced Raman spectroscopy (WERS) and waveguide infrared absorption spectroscopy (WIRAS). The development of integrated light sources and detectors toward miniaturization will be presented, together with the recent advances on waveguides and cladding to improve sensitivity. The latest reports on gas-sensing applications and main configurations for WERS and WIRAS will be described, and the most relevant figures of merit and limitations of different sensor realizations summarized.


Ultrasound-Guided Axillary Brachial Plexus Block for the Management of Graft Site Pain During Dressing Change in the Burn-Injured Patient: A Randomized Control Trial.
Burn injuries requiring split-thickness skin grafting procedures often require ongoing wound aggravation in the form of dressing changes. These dressing changes may cause significant pain due to stimulation of damaged nerve endings in the epidermal layer. A randomized control trial, pilot study, was undertaken to evaluate the impact of ultrasound-guided regional nerve block on the outcome of patient reported pain scores by inpatients requiring dressing changes for hand and upper limb burn injuries. Twenty participants aged >18 years, requiring split-skin grafting for burn injuries of <15% total body surface area were enrolled from a tertiary burns unit between August 2018 and September 2020. Participants were randomized to control (10 participants) or intervention group (10 participants). All participants received analgesia as per their treating team, the intervention group received the addition of an ultrasound-guided axillary brachial plexus block prior to their dressing change procedure. The primary outcome was to assess perceived pain at the graft site as measured by the Numeric Pain Rating Scale (0-10) before, during, and after dressing change procedure. There was strong evidence of a difference in the adjusted mean change score between groups, with a mean reduction of 4.3 in the intervention group, indicating reduced pain, and a mean increase of 1.2 in the control group (P < .001). No adverse events occurred in either group, and the addition of ultrasound-guided regional anesthesia (RA) for the treatment of dressing pain was determined to be a safe and effective intervention.


Acute Corneal Toxicity of Diquas.
This study aimed to investigate acute corneal toxicity of commercially available diquafosol 3% ophthalmic solution (Diquas®), which contains C12 benzalkonium chloride (BAC) as a preservative. Corneal transepithelial electrical resistance (TER) changes after a 60-second exposure to Diquas® (diquafosol 3% preserved with 0.0075% C12 BAC); 0.0075% C12 BAC and 0.0075% C12, C14, C16 BAC mixture were measured in living rabbits. Corneal damage was also examined by scanning electron microscopy (SEM). Hank's balanced salt solution (HBSS) was used as a control. Diquas® and 0.0075% C12 BAC did not produce any significant decrease in the corneal TER as compared to the HBSS control eyes. There was a significant decrease in the corneal TER after exposure of the cornea to the 0.0075% C12, C14, C16 BAC mixture (p < 0.01). SEM revealed that the superficial cells of the corneas exposed to the 0.0075% BAC mixture were damaged and exhibited degenerated microvilli. Conversely, the superficial cells of corneas exposed to Diquas® or 0.0075% C12 BAC appeared normal and had normal microvilli under SEM examinations. The acute corneal toxicity of Diquas® is less than that of the 0.0075% BAC mixture. Diquas® preserved with 0.0075% C12 BAC did not show acute corneal toxicity.


A VIT-like transporter facilitates iron transport into nodule symbiosomes for nitrogen fixation in soybean.
Effective legume-rhizobia symbiosis depends on efficient nutrient exchange. Rhizobia need to synthesize iron-containing proteins for symbiotic nitrogen fixation (SNF) in nodules, which depends on host plant-mediated iron uptake into the symbiosome. We functionally investigated a pair of vacuolar iron transporter like (VTL) genes, GmVTL1a/b, in soybean (Glycine max) and evaluated their contributions to SNF, including investigations of gene expression patterns, subcellular localization, and mutant phenotypes. Though both GmVTL1a/b genes were specifically expressed in the fixation zone of the nodule, GmVTL1a was the lone member to be localized at the tonoplast of tobacco protoplasts, and shown to facilitate ferrous iron transport in yeast. GmVTL1a targets the symbiosome in infected cells, as verified by in situ immunostaining. Two vtl1 knockout mutants had lower iron concentrations in nodule cell sap and peribacteroid units than in wild-type plants, suggesting that GmVTL1 knockout inhibited iron import into symbiosomes. Furthermore, GmVTL1 knockout minimally affected soybean growth under nonsymbiotic conditions, but dramatically impaired nodule development and SNF activity under nitrogen-limited and rhizobia-inoculation conditions, which eventually led to growth retardation. Taken together, these results demonstrate that GmVTL1a is indispensable for SNF in nodules as a transporter of ferrous iron from the infected root cell cytosol to the symbiosome.


Translational reinitiation: reinitiation of lac repressor fragments at three internal sites early in the lac i gene of Escherichia coli.
Three early amber mutations in the lac i gene have been shown to arise from the codons corresponding to residues 7, 12, and 17 of the lac repressor polypeptide chain. All three mutations allow translational reinitiation at the same two sites, resulting in the synthesis of two lac repressor fragments. The amino-terminal sequences of these fragments show that the first site is the triplet coding for valine residue 23, while the second is the first internal in-phase AUG codon corresponding to residue 42. Translational reinitiation appears to be a common event in E. coli, since there are at least three such sites in the first 70 in-phase codons of the i-gene messenger RNA, and all amber mutants found in this region show translational reinitiation. Only one of these sites involves an AUG codon; the other two involve an in vivo ambiguity of the genetic code, in that the same codon can be translated into two different amino acids depending on whether it is recognized during initiation or elongation of protein biosynthesis. The two non-AUG codons are the codons corresponding to leucine residue 62 and valine residue 23 of the lac repressor.


Volume threshold for chest tube removal: a randomized controlled trial.
Despite importance of chest tube insertion in chest trauma, there is no general agreement on the level of daily volume drainage from chest tube. This study was conducted to compare the effectiveness and safety of chest tube removal at the levels of 150 ml/day and 200 ml/day. Eligible patients (138) who needed replacement of chest tube (because of trauma or malignancy) were randomized into two groups; control (removal of chest tube when drainage reached to 150 ml/day) and trial (removal of chest tube at the level of 200 ml/day). All patients received standard care during hospital admission and a follow-up visit after 7 days of discharge from hospital. Patients were then compared in terms of major clinical outcomes using chi-squared and t-test. From the total of 138 patients, 70 and 68 patients were randomized to control (G150) and trial (G200) group, respectively. Baseline characteristics were comparable between the two groups. Although the trial group had a shorter mean for length of hospital stay (LOS) (4.1 compared to 4.8, p=0.04), their differences in drainage time did not reach to the level of statistical significance (p=0.1). Analysis of data showed no statistically significant differences between the rate of radiological reaccumulation, thoracentesis and decrease in pulmonary sounds (auscultatory), one week after discharge from hospital. Compared to a daily volume drainage of 150 ml, removal of chest tube when there is 200 ml/day is safe and will even result in a shorter hospital stay. This in turn leads to a lower cost.


Alternating monotherapy is the preferred treatment.
The choice of initial therapy of hypertensive patients may be critical in the long-term efforts to reduce premature cardiovascular morbidity and mortality. In the 1984 report of the third Joint National Committee (JNC), significant changes in the usual approach to initial therapy were suggested, including a more conservative approach toward the institution of drug therapy, more liberal use of nondrug therapies and broader choices for the initial drug. I support these changes and believe that even a greater number of choices for initial therapy should be considered. I am increasingly concerned about the hazards of diuretic therapy and believe that for most patients, an adrenergic inhibitor is preferable for first drug. Rather than limit the type of adrenergic inhibitor to a beta blocker as suggested in the JNC report, either an alpha blocker or a centrally acting drug may be preferable. In the near future, calcium antagonists will likely also become logical choices.


Protein binding of a DRPLA family through arginine-glutamic acid dipeptide repeats is enhanced by extended polyglutamine.
Dentatorubral-pallidoluysian atrophy (DRPLA) is one of the hereditary neurodegenerative disorders caused by expansion of CAG/glutamine repeats. To investigate the normal function of the DRPLA gene and the pathogenic mechanism of neuron death in specific areas of the brain, we isolated and analyzed a gene that shares a notable motif with DRPLA, arginine-glutamic acid (RE) dipeptide repeats. The gene isolated, designated RERE, has an open reading frame of 1566 amino acids, of which the C-terminal portion has 67% homology to DRPLA, whereas the N-terminal portion is distinctive. RERE also contains arginine-aspartic acid (RD) dipeptide repeats and putative nuclear localization signal sequences, but no polyglutamine tracts. RERE is expressed at a low level in most tissues examined. Immunoprecipitation and in vitro binding assays demonstrate that the DRPLA and RERE proteins bind each other, for which one of the RE repeats has a primary role, and extended polyglutamine enhances the binding. With engineered constructs fused with a tag, the RERE protein localized predominantly in the nucleus. Moreover, when RERE is overexpressed, the distribution of endogenous DRPLA protein alters from the diffused to the speckled pattern in the nucleus so as to co-localize with RERE. More RERE protein is recruited into nuclear aggregates of the DRPLA protein with extended polyglutamine than into those of pure polyglutamine. These results reveal a function for the DRPLA protein in the nucleus and the RE repeat in the protein-protein interaction.


Radial artery occlusion after transradial approach to cardiac catheterization.
Radial artery occlusion (RAO) is the most common complication of the transradial approach (TRA) to cardiac catheterization, with a reported incidence between 0.8 % and 30 %. RAO is likely the result of acute thrombus formation and complicated by neointimal hyperplasia. Most RAO are asymptomatic with rare cases of acute hand or digit ischemia reported in the literature. The role of testing for dual circulation to the hand in determining the safety of TRA as it relates to symptomatic RAO is controversial; however, modifiable risk factors like low sheath-to-artery ratio, adequate anticoagulation, and non-occlusive ("patent") hemostasis are likely to prevent RAO. This review examines the incidence of RAO, potential mechanisms leading to RAO, and strategies to prevent and treat RAO.


Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension.
Peroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12-14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.


HLA-B alleles B*15:01 and B*15:02: opposite association with hepatitis C virus infection in Chinese voluntary blood donors.
Although human leukocyte antigens (HLA) have been shown in association with the outcomes of hepatitis C virus (HCV) infection among different ethnic groups, such studies remain absent in China, where the HCV prevalence is higher than the global average. In this study, 426 HCV-infected and 709 uninfected blood donors were analyzed, among whom the HLA alleles were sequenced using a high-resolution genotyping method. At the 2-digit level, none of the alleles showed a statistical difference between the HCV-infected and uninfected groups. However, at the 4-digit level, the HLA-B alleles B*15:01 and B*15:02 showed an opposite association with HCV infection, i.e. B*15:01 was significantly higher in the HCV-infected group (odds ratio, OR = 1.561, p = 0.010), while B*15:02 was significantly higher in the uninfected group (OR = 0.778, p = 0.016). We also identified a higher frequency of B*13:02 in the HCV-infected group (OR = 1.515, p = 0.009) and a higher frequency of B*07:05 in the uninfected group (OR = 0.299, p = 0.001). The frequencies of four HLA alleles, B*07:05, B*13:02, B*15:01, and B*15:02, were found to be significantly different between the HCV-infected and uninfected blood donors in China, revealing an inverse relation of B*15:01 and B*15:02 with HCV infection. This finding suggests that the ethnic genetic variations of HLA may greatly affect the host immune responses against HCV.


Magnetic Resonance Imaging (MRI) and Hip Arthroscopy Correlations.
The hip is a complex joint which commonly generates referrals to orthoaedic surgeons. Hip arthroscopy continues to expand its indications for addressing hip pathology. Before operative intervention, the appropriate information must be obtained with magnetic resonance imaging playing a significant role in the workup given its outstanding characterization of soft tissue anatomy. We attempt to highlight multiple hip findings to correlate intraoperative arthroscopic findings with specific magnetic resonance imaging images and sequences.


Reduced Ca2+ spark activity contributes to detrusor overactivity of rats with partial bladder outlet obstruction.
We tested whether or not altered Ca2+ spark activity accounted for detrusor overactivity (DO) of Wistar rats after partial bladder outlet obstruction (PBOO). We constructed a DO model through PBOO and studied the Ca2+ spark activity of detrusor. By way of using confocal microscopy and the patch-clamp technique, Ca2+ sparks and spontaneous transient outward currents (STOCs) in detrusor myocytes were measured respectively. Our results indicated that Ca2+ spark activity and STOCs were significantly reduced in the DO detrusor myocytes compared to unafflicted control cells, and both of these had levels that were remarkably increased by applications of caffeine (10 μM), a RyR agonist, in DO myocytes. In addition, measures of detrusor contractions were also recorded by using freshly isolated detrusor strips. These results indicated that the spontaneous contraction of DO detrusor was significantly enhanced, and that the effect of caffeine (10 μM) upon detrusor contractions was reversed by applications of iberiotoxin (100 nM) which is a BK channel blocker. Western blotting (WB) analyses indicated that the levels of expression of ryanodine receptor type 2 (RyR2) and FK506 binding protein 12.6 (FKBP12.6) in bladder muscle were respectively decreased and increased in the samples from DO rats. Thus, we considered in the rat DO model wherein PBOO, the reduced Ca2+ spark activity in detrusor myocytes partly contributed to overactive detrusor contractions. The impaired Ca2+ spark activity may have resulted from decreased RyR2 expression and increased FKBP12.6 expression. Such novel findings in our research might help to provide means for better treatment outcomes for patients afflicted by bladder dysfunction.


Comparative metabolism of aspartame in experimental animals and humans.
Aspartame [SC-18862; 3-amino-N-(alpha-carboxyphenethyl) succinamic acid, methyl ester, the methyl ester of aspartylphenylalanine] is a sweetening agent that organoleptically has about 180 times the sweetness of sugar. The metabolism of aspartame has been studied in mice, rats, rabbits, dogs, monkeys, and humans. The compound was digested in all species in the same way as are natural constituents of the diet. Hydrolysis of the methyl group by intestinal esterases yielded methanol, which was oxidized in the one-carbon metabolic pool to CO2. The resultant dipeptide was split at the mucosal surface by dipeptidases and the free amino acids were absorbed. The aspartic acid moiety was transformed in large part to CO2 through its entry into the tricarboxylic acid cycle. Phenylalanine was primarily incorporated into body protein either unchanged or as its major metabolite, tyrosine.


Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits.
Multiple reports have documented an age-related loss, estimated at about 10% per decade, of the pigmented neurons in the substantia nigra. This is associated with motor dysfunction, including bradykinesia, stooped posture and gait disturbance. As microglia are activated by cell death and neuromelanin pigment, we hypothesized that there should be a significant microglial reaction in normal aging human substantia nigra. Sections of substantia nigra from elderly subjects (N = 15; mean 81.3; SD 7.0) and younger subjects (N = 7; mean 30.3; SD = 8.7), all of which had no specific neurologically or neuropathologically defined disorders, were stained immunohistochemically for MHC Class II and the area occupied by microglia was quantified in substantia nigra pars compacta. All elderly subjects showed a pronounced microglial reaction in the substantia nigra, with frequent, intensely stained hypertrophic microglia, while immunoreactive nigral microglia were much less frequent in the younger subjects. Quantification showed that in older subjects, the percentage of substantia nigra area occupied by microglial bodies and processes was significantly greater than for younger subjects (mean 19.6 vs. 3.6; P = 0.005). Extraneuronal neuromelanin deposits were present in all the older subjects but were absent or rare in the younger subjects. The neuromelanin deposit abundance score in the older subjects correlated significantly with the area occupied by immunoreactive microglia. The marked microglial reaction in normal aging human substantia nigra, together with the previously reported 35-80% pigmented neuron loss, indicates the presence of a powerful pathologic process that may be additive with specific age-related neurodegenerative diseases, including Parkinson's disease.


The Impact of Cat Fostering on Older Adult Well-Being and Loneliness: A Feasibility Study.
This feasibility study explored the impact of fostering a shelter cat on loneliness and well-being in older adults living alone without a pet. The study also examined the effect of cat fostering on older adults' interest in cat adoption when perceived barriers to adoption were removed. Twenty-nine adults (age >60) were paired with a cat and asked to foster for a minimum of 4 months (with an option to adopt). Participants completed surveys before placement with cats, with a follow-up at 1 and 4 months post-placement and 12 months if they adopted their cat. The survey included scales of loneliness, physical and mental health, self-efficacy, positive and negative affect, and comfort from a companion animal. Scores were compared across time using a multivariate Linear Mixed Model. Twenty-three of 29 (79.3%) participants remained in the study for at least 4 months, and a majority (95.7%) adopted their cat. Estimated mean differences in marginal means (adjusted for physical health) showed a significant improvement in loneliness from baseline to 4 months (p =0.029). A similar 4-month improvement that approached statistical significance (adjusted p = 0.079) was observed for mental health. No other scales showed statistically significant changes across time. Fostering a shelter cat with the option for adoption may be an effective solution for alleviating loneliness and improving mental health in older adults. Interest in adopting foster cats was high when perceived barriers to adoption were removed.


Combined exercise and insulin-like growth factor-1 supplementation induces neurogenesis in old rats, but do not attenuate age-associated DNA damage.
We have investigated the effects of 2 weeks of insulin-like growth factor-1 (IGF-1) supplementation (5 μg/kg per day) and 6 weeks of exercise training (60% of the maximal oxygen consumption [VO₂ max]) on neurogenesis, DNA damage/repair, and sirtuin content in the hippocampus of young (3 months old) and old (26 months old) rats. Exercise improved the spatial memory of the old group, but IGF-1 supplementation eliminated this effect. An age-associated decrease in neurogenesis was attenuated by exercise and IGF-1 treatment. Aging increased the levels of 8-oxo-7,8-dihydroguanine (8-oxoG) and the protein Ku70, indicating the role of DNA damage in age-related neuropathology. Acetylation of 8-oxoguanine DNA glycosylase (OGG1) was detected in vivo, and this decreased with aging. However, in young animals, exercise and IGF-1 treatment increased acetylated (ac) OGG1 levels. Sirtuin 1 (SIRT1) and SIRT3, as DNA damage-associated lysine deacetylases, were measured, and SIRT1 decreased with aging, resulting in a large increase in acetylated lysine residues in the hippocampus. On the other hand, SIRT3 increased with aging. Exercise-induced neurogenesis might not be a causative factor of increased spatial memory, because IGF-1 plus exercise can induce neurogenesis in the hippocampus of older rats. Data revealed that the age-associated increase in 8-oxoG levels is due to decreased acetylation of OGG1. Age-associated decreases in SIRT1 and the associated increase in lysine acetylation, in the hippocampus, could have significant impact on function and thus, could suggest a therapeutic target.


Caution or warning? A validity study of the MAYSI-2 with juvenile offenders.
Given the high prevalence of mental health and substance use disorders in the juvenile justice system and the emphasis on efficient screening and referrals, the current study sought to further validate the use of the Massachusetts Youth Screening Instrument version 2 (MAYSI-2). Using data from institutionalized delinquents (N=836) committed to the California Youth Authority, finite mixture modeling was employed to identify distinct latent classes based on MAYSI-2 scale scores. Identified classes were then compared across a range of covariates, including prior offenses, official records of misconduct, and multiple measures of mental health and psychological well-being. Findings revealed a three-class, gradient-based structure: low distress (n=380), moderate distress (n=327), and high distress (n=129). Overall, the MAYSI-2 identified juvenile offenders with mental health and substance use issues, but it did not differentiate youths with respect to offending patterns.


Prevalence of Chlamydia trachomatis in Pregnant Iranian Women: A Systematic Review and Meta-Analysis.
Several studies have been conducted regarding the prevalence of Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum in pregnant Iranian women. However, it is necessary to combine the previous results to present a general assessment. We conducted the present study based on systematic review and meta-analysis studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched the national and international online databases of MagIran, IranMedex, SID, MedLib, IranDoc, Scopus, PubMed, ISI Web of Knowledge, and Google Scholar search engine for certain MeSH keywords until June 16, 2017. In addition, heterogeneity, sensitivity analysis, subgroup analysis, and publication bias were performed. The data were analyzed using random-effects model and Comprehensive Meta-Analysis version 2 and P value was considered lower than 0.05. The prevalence of Chlamydia trachomatis in 11 surveyed articles that assessed 2864 pregnant Iranian women was 8.74% [95% confidence interval (CI): 5.40-13.84]. The prevalence of Chlamydia trachomatis was estimated 5.73% (95% CI: 2.09-14.73) and 13.55% (95% CI: 11.23-16.25) by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), respectively which the difference was not significant (P=0.082). The lowest and highest prevalence of Chlamydia trachomatis was estimated in Tehran province [4.96% (95% CI: 2.45-9.810)] and Ardabil province [28.60% (95% CI: 20.61-38.20)], respectively. This difference was statistically significant (P<0.001). Meta-regression for the prevalence of Chlamydia trachomatis based on year of the studies was significant with increasing slope (P=0.017). According to the systematic review, the prevalence of Mycoplasma hominis and Urea plasma urealyticum indicated 2 to 22.8% (from 4 articles) and 9.1 to 19.8% (from 3 articles), respectively. There was no evidence of publication bias (P value for Begg and Eggers' tests was 0.161 and 0.173, respectively). The prevalence of Chlamydia trachomatis is high among pregnant Iranian women. Screening pregnant women as part of preventive measures seem necessary considering the potential for maternal and fetal complications.


Crystal structure of the pleckstrin homology domain from the ceramide transfer protein: implications for conformational change upon ligand binding.
Ceramide transfer protein (CERT) is responsible for the nonvesicular trafficking of ceramide from the endoplasmic reticulum (ER) to the trans Golgi network where it is converted to sphingomyelin (SM). The N-terminal pleckstrin homology (PH) domain is required for Golgi targeting of CERT by recognizing the phosphatidylinositol 4-phosphate (PtdIns(4)P) enriched in the Golgi membrane. We report a crystal structure of the CERT PH domain. This structure contains a sulfate that is hydrogen bonded with residues in the canonical ligand-binding pocket of PH domains. Our nuclear magnetic resonance (NMR) chemical shift perturbation (CSP) analyses show sulfate association with CERT PH protein resembles that of PtdIns(4)P, suggesting that the sulfate bound structure likely mimics the holo form of CERT PH protein. Comparison of the sulfate bound structure with the apo form solution structure shows structural rearrangements likely occur upon ligand binding, suggesting conformational flexibility in the ligand-binding pocket. This structural flexibility likely explains CERT PH domain's low affinity for PtdIns(4)P, a property that is distinct from many other PH domains that bind to their phosphoinositide ligands tightly. This unique structural feature of CERT PH domain is probably tailored towards the transfer activity of CERT protein where it needs to shuttle between ER and Golgi and therefore requires short resident time on ER and Golgi membranes.


Factors associated with the use of various medications amongst patients with severe coronary artery disease. SECOR/SBU Project Group.
To describe variations by age, sex, symptom severity and hospital region in the use of various medications amongst patients with stable angina pectoris who are candidates for coronary revascularization. Patients (n = 2030) with chronic stable angina pectoris participating in a national survey evaluating the appropriateness of the use of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG). As part of a national study of the appropriateness of coronary revascularization, data were prospectively collected on patients referred for consideration of coronary revascularization to seven of the eight public Swedish heart centres that performed approximately 92% of all bypass operations in Sweden in 1994. Amongst all patients 76% were treated with beta blockers, 41% with calcium antagonists and 71% with long-acting nitrates and 70% were treated with at least two of these three drugs. Eighty-two per cent of the patients used aspirin and 14% lipid-lowering drugs. According to logistic regression analysis, with medication as the dependent variable and independent variables of age, sex, angina functional class, findings at exercise test, history of various diseases and region in Sweden where the investigation took place, the most consistent factor explaining the use of various medications was found to be geographical region. A previous history of acute myocardial infarction (AMI) was also associated with the use of all drugs and age was associated with all with the exception of beta blockers. Sex was not an independent factor explaining the use of any of the drugs. In a national survey including patients with stable angina pectoris who are potential candidates for coronary revascularization, the most important predictor for the use of various medications was the geographical region in which the investigation took place.


Effect of Pulpotomy Procedures With Mineral Trioxide Aggregate and Dexamethasone on Post-endodontic Pain in Patients with Irreversible Pulpitis: A Randomized Clinical Trial.
Endodontic post-treatment pain continues to be one of the main problems encountered by dental professionals. Therefore, pain control during and after endodontic treatment is one of the most important issues in endodontics. The purpose of this clinical trial was to compare postoperative pain relief achieved with dexamethasone (DEX) and mineral trioxide aggregate (MTA) used as pulp coverage after pulpotomy in human molars with irreversible pulpitis. This prospective double-blind study was conducted on 54 patients complaining of dental pain due to irreversible pulpitis. The standard pulpotomy procedure was performed by the same dentist in all patients. At the time of the cotton pellet placement, patients were randomly divided into three groups: those in whom a sterile dry cotton (DC) pellet was used, patients treated with a cotton pellet soaked in MTA, and those who were treated with a cotton pellet soaked in DEX. After completion of the treatment, patients received rescue medication every 6 hours for the first day. Postoperative pain was assessed at 6-hour intervals for 24 hours, and then every day until day 7 using a visual analog scale. In general, patients treated with MTA suffered the lowest levels of pain at all time intervals. Post-pulpotomy pain was significantly reduced at 18 and 24 hours and from days 2 to 7 post-treatment in the MTA group. DEX lowered the pain level more than the DC pellet. However, the differences observed in the mean pain scores of the DEX and DC pellet groups at all-time intervals were not statistically significant. Pulpotomy procedures can reduce pain related irreversible pulpitis. Pulpotomy with MTA-soaked cotton pellet significantly reduces pain intensity in patients with irreversible pulpitis.


Factors associated with medical students' career choices at a private university: a cross-sectional study.
This study aimed to identify the factors associated with students' career choices and the decision whether they wanted to be trained abroad or in Pakistan. The study utilised a cross-sectional design and was conducted between July 2021 and February 2022. An anonymous survey was distributed among the medical students at Aga Khan University, Karachi, Pakistan. All analysis was carried out using Stata 17. A total of 269 students participated in the study. The most sought-after specialties were surgery 68 (25.3%), medicine 25(9.3%), and paediatrics 14(5.2%), and the decision was highly influenced by positive mentors and lifestyle. In addition, 259 (96%) of the students expressed a desire to practice abroad for training due to higher financial prospects and quality of training. This study revealed that providing enthusiastic mentors may encourage medical students to pursue a broader range of specialties. Furthermore, there is a need for advances in postgraduate training and increase in salaries to restore trust in Pakistan's healthcare system.


[Liver cell carcinoma--pathomorphology and differential diagnosis].
Modern imaging techniques permit the detection of small and smaller nodular lesions of the liver. The classification and differential diagnosis of these lesions is still mainly based on pathomorphological analysis. With the exception of metastases from extra-hepatic malignant tumors, hepatocellular carcinoma is the most frequent malignant tumor of the liver. Whereas the classical variant of hepatocellular carcinoma preferentially arises in the cirrhotic liver, the fibrolamellar variant is found without association to cirrhosis and hepatitis B infection in the liver of young adults. Differential diagnosis of hepatocellular nodular lesions includes focal fatty change, focal nodular hyperplasia, liver cell adenoma, large regenerative nodules and dysplastic nodular lesions.


Diffuse charge dynamics in ionic thermoelectrochemical systems.
Thermoelectrics are increasingly being studied as promising electrical generators in the ongoing search for alternative energy sources. In particular, recent experimental work has examined thermoelectric materials containing ionic charge carriers; however, the majority of mathematical modeling has been focused on their steady-state behavior. Here, we determine the time scales over which the diffuse charge dynamics in ionic thermoelectrochemical systems occur by analyzing the simplest model thermoelectric cell: a binary electrolyte between two parallel, blocking electrodes. We consider the application of a temperature gradient across the device while the electrodes remain electrically isolated from each other. This results in a net voltage, called the thermovoltage, via the Seebeck effect. At the same time, the Soret effect results in migration of the ions toward the cold electrode. The charge dynamics are described mathematically by the Poisson-Nernst-Planck equations for dilute solutions, in which the ion flux is driven by electromigration, Brownian diffusion, and thermal diffusion under a temperature gradient. The temperature evolves according to the heat equation. This nonlinear set of equations is linearized in the (experimentally relevant) limit of a "weak" temperature gradient. From this, we show that the time scale on which the thermovoltage develops is the Debye time, 1/Dκ^{2}, where D is the Brownian diffusion coefficient of both ion species, and κ^{-1} is the Debye length. However, the concentration gradient due to the Soret effect develops on the bulk diffusion time, L^{2}/D, where L is the distance between the electrodes. For thin diffuse layers, which is the condition under which most real devices operate, the Debye time is orders of magnitude less than the diffusion time. Therefore, rather surprisingly, the majority of ion motion occurs after the steady thermovoltage has developed. Moreover, the dynamics are independent of the thermal diffusion coefficients, which simply set the magnitude of the steady-state thermovoltage.


Improving Family Presence in Long-Term Care during the COVID-19 Pandemic.
Family caregivers play a vital role in supporting the physical and mental health of long-term care (LTC) residents. Due to LTC visitor restrictions during the COVID-19 pandemic, residents (as well as family caregivers) showed significant adverse health outcomes due to a lack of family presence. To respond to these outcomes, eight implementation science teams led research projects in conjunction with Canadian LTC homes to promote the implementation of interventions to improve family presence. Overall, technological and virtual innovations, increased funding to the sector and partnerships with family caregivers were deemed effective methods to promote stronger family presence within LTC.