Off-center yaw rotation: effect of naso-occipital linear acceleration on the nystagmus response of normal human subjects and patients after unilateral vestibular loss.
Dual search coils were used to record horizontal, vertical and torsional eye movement components of one eye during nystagmus caused by off-center yaw rotation (yaw centrifugation). Both normal healthy human subjects (n=7) and patients with only one functioning labyrinth (n=12) were studied in order to clarify how the concomitant linear acceleration affected the nystagmus response. Each subject was seated with head erect on the arm of a fixed-chair human centrifuge, 1 m away from the center of the rotation, and positioned to be facing along a radius; either towards (facing-in) or away from (facing-out) the center of rotation. Both yaw right and yaw left angular accelerations of 10 degrees s(-2) from 0 to 200 degrees/s were studied. During rotation a centripetal linear acceleration (increasing from 0 to 1.24xg units) was directed along the subject's naso-occipital axis resulting in a shift of the resultant angle of the gravitoinertial acceleration (GIA) of 51 degrees in the subject's pitch plane and an increase in the total GIA magnitude from 1.0 to 1.59xg. In normal subjects during the angular acceleration off-center there were, in addition to the horizontal eye velocity components, torsional and vertical eye velocities present. The magnitude of these additional components, although small, was larger than observed during similar experiments with on-center angular acceleration (Haslwanter et al. 1996), and the change in these components is attributed to the additional effect of the linear acceleration stimulation. In the pitch plane the average size of the shift of the axis of eye velocity (AEV) during the acceleration was about 8 degrees for a 51 degrees shift of the GIA (around 16% of the GIA shift) so that the AEV-GIA alignment was inadequate. There was a very marked difference in the size of the AEV shift depending on whether the person was facing-in [AEV shift forward (i.e. non-compensatory) of about 4 degrees] or facing-out [AEV shift forward (i.e. compensatory) of around 12 degrees]. The linear acceleration decreased the time constant of decay of the horizontal component of the post-rotatory nystagmus: from an average of 24.8 degrees/s facing-in to an average of 11.3 degrees/s facing-out. The linear acceleration dumps torsional eye velocity in an manner analogous to, but independent of, the dumping of horizontal eye velocity. Patients with UVD had dramatically reduced torsional eye velocities for both facing-in and facing-out headings, and there was little if any shift of the AEV in UVD patients. The relatively small effects of linear acceleration on human canal-induced nystagmus found here confirms other recent studies in humans (Fetter et al. 1996) in contrast to evidence from monkeys and emphasizes the large and important differences between humans and monkeys in otolith-canal interaction. Our results confirm the vestibular control of the axis of eye velocity of humans is essentially head-referenced whereas in monkeys that control is essentially space-referenced.


Ability of lupine seeds to germinate and to tolerate desiccation as related to changes in free radical level and antioxidants in freshly harvested seeds.
Seeds of yellow lupine (Lupinus luteus L. cv. Juno) were collected throughout their development on the mother plant to determine whether the ability to germinate and to tolerate desiccation is related to the level of free radicals and the changes in the redox state of ascorbate and glutathione as well as the activities of antioxidative enzymes. Electron paramagnetic resonance (EPR)-based analyses showed that development of lupine seed was accompanied by generation of free radicals with g(1) and g(2) values of 2.0049+/-0.0004 and 2.0029+/-0.0003, respectively. Free radical level increased significantly 25 DAF and decreased thereafter. The amount of hydrogen peroxide was high in fresh immature seeds and decreased during maturation drying. Ascorbate accumulated in lupine embryos during early seed filling stage whereas glutathione content increased during late seed filling phase. During maturation drying the redox state of both ascorbate and glutathione pools shifted towards the oxidized forms. While superoxide dismutase (SOD, EC 184.108.40.206), and ascorbate peroxidase (APX, EC 126.96.36.199) activities remained high at the early seed filling stage the activities of both dehydroascorbate reductase (DHAR, EC 126.96.36.199) and glutathione reductase (GR, EC 184.108.40.206) and that of catalase (CAT, EC 188.8.131.52) increased before seeds reached physiological maturity and decreased thereafter. The changes of isoform patterns of antioxidative enzymes were observed during seed maturation. Immature lupine seeds tested immediately after harvest acquired the ability to germinate when less than half-filled and reached high tolerance to desiccation just after physiological maturity. The physiological implications of the changes in antioxidative machinery for the acquisition of desiccation tolerance and seeds germinability are discussed.


Sensitivity to changes during antidepressant treatment: a comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal depression.
In the efficacy evaluation of antidepressant treatments, the total score of the Hamilton Depression Rating Scale (HAMD) is still regarded as the 'gold standard'. We previously had shown that the Inventory of Depressive Symptomatology (IDS) was more sensitive to detect depressive symptom changes than the HAMD17 (Helmreich et al. 2011). Furthermore, studies suggest that the unidimensional subscales of the HAMD, which capture the core depressive symptoms, outperform the full HAMD regarding the detection of antidepressant treatment effects. The aim of the present study was to compare several unidimensional subscales of the HAMD and the IDS regarding their sensitivity to changes in depression symptoms in a sample of patients with mild major, minor or subsyndromal depression (MIND). Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course. We investigated sensitivity to depressive change for all scales from assessment-to-assessment, in relation to depression severity level and placebo-verum differences. The subscales performed similarly during the treatment course, with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included. Most changes in depressive symptomatology were detected by the IDS short scale, but regarding the effect sizes, it performed worse than most subscales. Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes, especially in antidepressant treatment efficacy studies. However, subscales do not cover all facets of depression (e.g. atypical symptoms, sleep disturbances), which might be important for comprehensively understanding the nature of the disease depression. Therefore, the cost-to-benefit ratio must be carefully assessed in the decision for using unidimensional subscales.


A graphical method to analyze serum tumor marker decay in nonseminomatous testis tumors.
The decay pattern and half-life estimation of serum tumor markers are useful parameters in the management of nonseminomatous germ cell tumors of the testis. We describe a graphical method of evaluating the temporal pattern of tumor marker clearance that can be used to identify patients with residual tumor after orchiectomy alone or retroperitoneal lymphadenectomy.


The septate junction component bark beetle is required for Drosophila intestinal barrier function and homeostasis.
Age-related loss of intestinal barrier function has been documented across species, but the causes remain unknown. The intestinal barrier is maintained by tight junctions (TJs) in mammals and septate junctions (SJs) in insects. Specialized TJs/SJs, called tricellular junctions (TCJs), are located at the nexus of three adjacent cells, and we have shown that aging results in changes to TCJs in intestines of adult Drosophila melanogaster. We now demonstrate that localization of the TCJ protein bark beetle (Bark) decreases in aged flies. Depletion of bark from enterocytes in young flies led to hallmarks of intestinal aging and shortened lifespan, whereas depletion of bark in progenitor cells reduced Notch activity, biasing differentiation toward the secretory lineage. Our data implicate Bark in EC maturation and maintenance of intestinal barrier integrity. Understanding the assembly and maintenance of TCJs to ensure barrier integrity may lead to strategies to improve tissue integrity when function is compromised.


Pathological changes of anastomotic false aneurysms.
Anastomotic parts of polyester vascular prostheses implanted in thoracic aortae of 270 dogs were examined. Anastomotic false aneurysms were seen with 3 cases (1.2%), in which disruption did not occur, however, the grafts which have no aneurysm showed the following features, i.e., suture migration, degenerative changes of the host arterial wall sustaining a suture and dissection between the host arterial wall and a prosthesis. From the results of an analysis of the arrangement pattern of smooth muscle cells in neointima, it was clarified that a suture had been subjected to continuous tensile stress. So that, the host arterial wall sustaining a suture is clinched and pulled toward prosthesis by the suture at every pulsation during implantation. These results indicate that the features mentioned above are phenomena of the developing into anastomotic false aneurysms.


Potential wrong-level surgery for an intra-dural thoracic spinal tumour: the importance of optimum imaging and consistency in the direction in which the level is determined.
The spectre of wrong-level surgery has many a spinal surgeon double-checking the spinal level at which an operation is being carried out especially in the thoracic spine, in the absence of abnormal-looking vertebrae which could help to identify the intended level. Getting the level wrong is easily done if there is an unusual number of vertebrae or if the direction of the count digresses from the imaging available.


Long-term effect of the combination of calcium clofibrate and calcium carbonate on serum total cholesterol, triglyceride and high density lipoprotein--cholesterol concentrations in hyperlipoproteinaemia. A comparative study with clofibrate.
Thirty hyperlipidaemic patients (19 with type IIA, 4 with IIB and 7 with type IV hyperlipoproteinaemia) were subjected to therapy with calcium clofibrate and calcium carbonate (4C, 2 + 2 g/day for 6 months) and the effect was compared with clofibrate (1C, 2 g/day) which was given for 6 months as well, in a single-blind placebo-controlled study. 4C and 1C decreased total serum cholesterol levels especially in subgroups IIA and IIB. 4C was somewhat more effective than 1C in decreasing (VLDL + LDL)-cholesterol in subgroup IIA. The HDL-cholesterol concentrations and the ratio of HDL-cholesterol and total cholesterol increased during treatment with both 1C and 4C. The HDL-cholesterol increase (vs. placebo) was 18%. The concentrations of serum triglycerides decreased by 33% during both treatment periods and there was no significant difference between 1C and 4C.


The effect of pre-pandemic PTSD and depression symptoms on mental distress among older adults during COVID-19.
To explore the extent that pre-COVID-19 comorbid PTSD-depression symptoms prospectively predict mental distress among older adults during COVID-19. We used the Israeli component of the Survey of Health, Ageing and Retirement in Europe (SHARE-Israel), and focused on older adults who participated in 2015 and 2020 and were aged 60 years old or above in 2020 (N = 754). Mental distress was measured via symptoms of depression, feeling anxious\nervous, and loneliness. Older adults who suffered from PTSD-depression comorbidity prior to the pandemic showed the highest risk of feeling more depressed, anxious\nervous, and lonelier than those with no pre-pandemic symptoms. This study suggests that it would be beneficial to prioritize those older adults with a comorbid PTSD-depression diagnosis for interventions, as they are at the highest risk for mental distress in the event of a new stressor.


Localization of (99m)Tc-Labeled ApoB Synthetic Peptide in Arterial Lesions of an Experimental Model of Spontaneous Atherosclerosis.
We have previously shown that after administration of (123)I-SP-4 (a synthetic ApoB peptide fragment) to Watanabe heritable hyperlipidemic (WHHL) rabbits that foci of tracer uptake can be identified by external gamma camera imaging which correspond to regions of the aortas found to contain abundant atherosclerotic lesions at postmortem evaluation. Because (99m)Tc is preferred over (123)I for scintigraphic imaging, we prepared a (99m)Tc-labeled form of the SP-4 peptide, designated (99m)Tc-P199. To assess the feasibility of detecting atherosclerotic lesions using (99m)Tc-P199 and to compare the relative uptake of the (99m)Tc-labeled and radioiodinated peptides by such lesions, an admixture of (99m)Tc-199 and (125)I-SP-4 was administered to 11 WHHL and 2 normal rabbits. These animals were imaged for up to 3 h and were sacrificed 3--4 h after injection. The extent of aortic lesion involvement and radiotracer uptake were quantitatively compared by planimetric analysis of photographs of the endothelial surface, (99m)Tc-P199 ex vivo images and (125)I-SP-4 autoradiograms of the excised aortas. Pairwise correlation coefficients for planimetric analysis were as follows: photographs versus ex vivo images, r = 0.83, p = 0.003; photographs versus autoradiograms, r = 0.87, p = 0.001; ex vivo images versus autoradiograms, r = 0.83, p = 0.003. (99m)Tc-199 in vivo gamma camera images revealed relatively weak focal aortic uptake in 8 of 11 WHHL rabbits manifesting aortic lesions, and focal carotid artery uptake in 4 of 6 WHHL rabbits manifesting carotid lesions. Neither aortic nor carotid foci were visualized in the normal rabbits. We conclude that (99m)Tc-199 localizes specifically in atherosclerotic lesions and may be useful for external imaging of atherosclerosis.


Dual GIP-GLP1-Receptor Agonists In The Treatment Of Type 2 Diabetes: A Short Review On Emerging Data And Therapeutic Potential.
The need for efficient and safe therapy to improve such metabolic diseases as obesity and type 2 diabetes mellitus is currently unmet. The development of dual GIPR-GLP1R coagonists that bind to either one or the other receptor (sequence-mixed dual agonists) has emerged as an innovative therapeutic strategy for obesity and type 2 diabetes. Combined activation of both receptors may act synergistically providing additive effects on glucose and body weight in comparison of GLP1 analogues alone. Preclinical studies have confirmed that GIPR-GLP1R coagonists improve several hallmarks of metabolic syndrome, such as obesity, hyperglycemia, and dyslipidemia. These metabolic benefits have been translated from mice to nonhuman primates and humans. Recent clinical trials have shown that coagonists induce significant benefits on body weight, fasting, and postprandial glucose levels, insulin sensitivity, and total cholesterol. Combined GIP- and GLP1R activators have the potential to become a treatment option for patients with type 2 diabetes.


Animal models for studying neural crest development: is the mouse different?
The neural crest is a uniquely vertebrate cell type and has been well studied in a number of model systems. Zebrafish, Xenopus and chick embryos largely show consistent requirements for specific genes in early steps of neural crest development. By contrast, knockouts of homologous genes in the mouse often do not exhibit comparable early neural crest phenotypes. In this Spotlight article, we discuss these species-specific differences, suggest possible explanations for the divergent phenotypes in mouse and urge the community to consider these issues and the need for further research in complementary systems.


Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series.
Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene. In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause. Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations. We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia.


Investigation of I1-imidazoline receptors using microphysiometry and molecular modelling.
The molecular identity and structure of imidazoline receptors is still poorly understood. For example the I1-imidazoline binding site (I1-site) is localised to the plasma membrane, but it is not clear if this represents a conventional receptor. The I1-site reportedly has both high and low affinity binding states. Again it is not clear if these sites represent different states of the same receptor, or distinct molecular entities. The signal transduction mechanisms of I1-imidazoline receptors are beginning to be unravelled. There is clear evidence that ligands with high affinity for I1-sites stimulate phosphatidylcholine-selective phospholipase C in the rat adrenal medullary tumour cell line PC-12, but this may not be the case in all cell types. We investigated the possible role of this novel pathway in bovine adrenal medullary cells. Radioligand binding studies with [3H]clonidine confirmed the presence of I1-sites in membranes from these cells. Using microphysiometry, a recently developed technique for determining cellular activation, the extracellular acidification rates of cultured bovine adrenal medullary cells were unaffected by a number of imidazolines considered to be agonists at the I1-site. This suggests that there is no I1-site mediated stimulation of phosphatidylcholine specific phospholipase C in these cells. However, nicotine-stimulated increases in extracellular acidification were blocked by 100 microM clonidine. Ion channels have been suggested as another possible I1-imidazoline 'receptor' family, and may represent the low affinity I1-site detected in binding studies. I1-Site ligands can be shown to bind to, or block, several members of the ligand-gated ion channel superfamily, including the 5HT3, K+ATP, NMDA and nicotinic acetylcholine receptors. The I1-site ligands appear to be binding to, and acting at, the previously described phencyclidine binding site in these channels. Furthermore, molecular modelling suggests that I1-site selective ligands share a common three-dimensional structure with phencyclidine, and that I2-site selective ligands do not have this structure. This suggests that a phencyclidine-binding site motif may represent a novel site of action for I1-site ligands, and a search for receptors based on this motif may reveal novel imidazoline 'receptors'.


Differences in the nuclear chromatin among various stages of the life cycle of Trypanosoma cruzi.
Trypanosoma cruzi is the etiological agent of Chagas. Although the nuclear chromatin of this parasite is organized in the form of nucleosome filaments, its chromatin is physically and enzymatically fragile, and no condensation into chromosomes occurs during mitosis. All previous investigations have been carried out with epimastigote form in its proliferate stage. It is not known whether these differences in chromatin structure are also found in the non-proliferate stationary epimastigote forms and in tissue derived trypomastigotes. Our results confirm that chromatin of logarithmic epimastigotes presents limited compaction when increasing salt concentrations from 1 to 100 mM NaCl, and no 30-nm fibers were formed. Contrary to these results, non-proliferative forms of the parasites showed a pattern of compactation similar to that observed in rat liver chromatin, where solenoids of 30-nm fibers are formed at 100-mM NaCl. In accordance with these results, digestion of the nuclear chromatin with DNase I revealed that the chromatin of logarithmic phase epimastigotes was more accessible to the enzyme. We conclude from these results that structural differences in the chromatin exist not only between T. cruzi and higher eukaryotes but also among various forms of the parasite. The functional significance of these differences are currently under investigation.


Preparation and evaluation of rotigotine-loaded implant for the treatment of Parkinson's disease and its evolution study.
To develop rotigotine-loaded implants (RI) to achieve continuous release of rotigotine for long duration for the treatment of Parkinson's disease (PD). RI was prepared by hot-melt extrusion method using poly (lactide-co-glycolide) (PLGA) as the matrix. In vitro drug release was optimized by drug loading, melting temperature during preparing process and additives. The surface and internal morphology of RI was imaged by SEM. The in vivo release profile of RI was investigated on rat. RI prepared with PLGA 7525 5A showed sustained release of 40 days while suffering a lag phase, which was significantly shortened by blending 5050 2A and mannitol in the matrix. RI prepared by 7525 5A/5050 2A/mannitol = 55:10:5 (rotigotine 30%) showed a 40-day sustained release in vivo with no lag phase. The drug release from RI was also affected by drug loading and melting temperature probably due to the drug state existed in the implant. The evolution of implants during release process was correlated well with the drug release kinetics. RI could achieve sustained drug release for 40 days which could supply an alternative of continuous dopaminergic stimulation (CDS) for the treatment of PD.


Autoimmune insulin syndrome.
Initially described in Japan, the autoimmune insulin syndrome is caused by the presence of anti-insulin antibodies in patients who have never received insulin. This syndrome accounts for spontaneous or reactive hypoglycaemia with very high levels of total immuno-reactive insulin. Discordance between the levels of immunoreactive insulin and C peptide indicate the possible presence of anti-insulin antibodies; this can avoid an incorrect diagnosis of insulinoma. These autoimmune hypoglycaemias often present a difficult diagnostic problem in distinguishing them from factitious hypoglycaemia. The course of the autoimmune insulin syndrome is usually favourable, with a spontaneous rapid diminution of the levels of anti-insulin antibodies. The reasons for the appearance of anti-insulin antibodies and the exact mechanisms of the hypoglycaemia remain uncertain. However, the frequent association of the autoimmune insulin syndrome with certain autoimmune diseases suggest a common immune dysfunction. Drugs containing a sulphydryl group have been implicated in the aetiology of this syndrome.


Physical restraint within the prehospital Emergency Medical Care Environment: A scoping review.
Psychomotor agitation and aggressive behaviour (AAB) have the potential to occur in any healthcare setting, including those in which Emergency Medical Services (EMS) operate. This scoping review aimed to examine the available literature on physical restraint of patients within the prehospital setting and to identify guidelines and their effectiveness, safety to patients and health care practitioners and strategies relating to physical restraint when used by EMS. We performed our scoping review using the methodological framework described by Arksey and O'Malley augmented by that of Sucharew and Macaluso. Several steps guided the review process: identification of the research question, eligibility criteria, information sources (CINAHL, Medline, Cochrane and Scopus), search, selection and data collection, ethical approval, collation, summarizing and reporting on the results. The population of interest, in this scoping review was prehospital physically restrained patients, however, there was a reduced research focus on this population in comparison to the larger emergency department. The limitation of informed consent from incapacitated patients may relate to the lack of prospective real-world research from previous and future studies. Future research should focus on patient management, adverse events, practitioner risk, policy, and education within the prehospital setting.


Serum erythrocyte sedimentation rate is higher among ethnic South Asian compared to ethnic Chinese ischemic stroke patients. Is this attributable to metabolic syndrome or central obesity?
Inflammation, a vascular risk factor, is more pronounced among ethnic South Asians compared to ethnic Chinese in the general population. We compared serum erythrocyte sedimentation rate (ESR) levels between ethnic South Asian and Chinese acute ischemic stroke patients, and further investigated if metabolic syndrome or central obesity could account for any difference detected. We prospectively recruited consecutive ischemic stroke patients within seven days of onset. Measurement of serum ESR was performed within two days of admission. Median serum ESR was higher among the 55 ethnic South Asian (16 mm/h IQR 3-35) compared to the 165 ethnic Chinese patients (9 mm/h IQR 4-19), p=0.004). Serum ESR was correlated with age. Higher serum ESR was associated with female gender, non-smokers, patients with central obesity and low high-density lipoprotein (HDL) cholesterol. Using regression analysis, South Asian ethnicity remained significantly associated with serum ESR, independent of age, gender, smoking status, metabolic syndrome, central obesity and low HDL. Ethnic South Asian ischemic stroke patients have a higher inflammatory state compared to ethnic Chinese patients. As the higher inflammatory state is independent of demographic and risk factors, we propose an underlying genetic or cultural basis for the ethnic difference.


Evolutionary study of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emerging coronavirus: Phylogenetic analysis and literature review.
Since emerging coronaviruses have always become a human health concern globally especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV) and Middle East respiratory syndrome coronavirus and a novel coronavirus was introduced in Wuhan, China, in December 2019 (called SARS-CoV-2), many researchers focused on its epidemics, virological and clinical features. SARS-CoV-2 is classified as Betacoronaviruses genus and Sarbecovirus subgenus (lineage B). The virus shows a great similarity with SARS-CoV and bat SARS-like coronaviruses. In this study, we evaluate SARS-CoV-2 virus phylogeny and evolution by using current virus and related sequences.


Investigation of an outbreak of central venous catheter-associated bloodstream infection due to contaminated water.
An outbreak of central venous catheter-associated bloodstream infections was reported in a hospital in Ecuador. Commercially produced ampoules of water for injection were found to be contaminated with Burkholderia cepacia and Myroides odoratus. Removal of these ampoules yielded a 10-fold reduction in the incidence of catheter-associated infection.


Up-regulation of Siah1 by ethanol triggers apoptosis in neural crest cells through p38 MAPK-mediated activation of p53 signaling pathway.
Seven in absentia homolog 1 (Siah1) is one of the E3 ubiquitin ligases and plays a key role in regulating target protein degradation. This study was designed to test the hypothesis that Siah1 mediates ethanol-induced apoptosis in NCCs through p38 MAPK-mediated activation of the p53 signaling pathway. We found that exposure of NCCs to ethanol resulted in the increases in the total protein levels of p53 and the phosphorylation of p53 at serine 15. Ethanol exposure also resulted in a significant increase in the phosphorylation of p38 MAPK. Knock-down of Siah1 dramatically reduced the ethanol-induced increase in the phosphorylation of p38 MAPK. Knock-down of Siah1 by siRNA or down-regulation of p38 MAPK by either siRNA or inhibitor significantly diminished ethanol-induced accumulations of p53 and the phosphorylation of p53. In addition, ethanol exposure resulted in a significant increase in the expression of p53 downstream targets and apoptosis in NCCs, which can be significantly diminished by down-regulation of Siah1 with siRNA. Knock-down of p38 MAPK by siRNA also dramatically reduced the ethanol-induced apoptosis. These results demonstrate that Siah1 plays a crucial role in ethanol-induced apoptosis in NCCs, and that the up-regulation of Siah1 by ethanol can trigger apoptosis through p38 MAPK-mediated activation of the p53 signaling pathway.


Development of pemphigus herpetiformis in a patient with psoriasis receiving UV-light treatment.
Pemphigus is an autoimmune blistering disease of the skin and mucous membranes. Pemphigus herpetiformis, a rare variant of pemphigus, is characterized by erythematous, vesicular, bullous, or papular lesions in a herpetiform pattern, often associated with pruritus. Clinical cases documenting the development of pemphigus in patients with a history of psoriasis have been reported in the literature. We used immunological methods to study a case in which pemphigus herpetiformis occurred in a woman with a history of psoriasis, shortly after a course of ultraviolet B (UVB) therapy. Histopathology revealed a subcorneal blister with prominent neutrophilic infiltration. Immunopathology detected in situ bound and circulating immunoglobulin G (IgG) autoantibodies to epithelial cell surfaces and circulating IgG autoantibodies against desmoglein 1. The patient was also found to have Hashimoto's thyroiditis. This case illuminates a possible role of UV therapy in the induction of pemphigus herpetiformis through an epitope-spreading mechanism. The patient's autoimmune thyroiditis may also contribute to the predisposition for pemphigus development. The histopathological findings in pemphigus patients with a history of psoriasis may resemble Munro's microabscesses of psoriasis and should therefore alert pathologists and clinicians in considering additional diagnostic methods such as direct and indirect immunofluorescence.


Exploring the links among inflammation and gut microbiome with psychoneurological symptoms and gastrointestinal toxicities in gynecologic cancers: a systematic review.
Emerging evidence highlights the roles the gut microbiome and the immune system, integral parts of the gut-brain axis, play in developing various symptoms in cancer patients. The purpose of this systematic review was to describe the roles of inflammatory markers and the gut microbiome, as well as to describe their associations with psychoneurological symptoms and gastrointestinal toxicities in women with gynecologic cancers. A comprehensive literature search was conducted in PubMed, Embase, and Web of Science from January 2000 to February 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were utilized to screen the found articles. The quality of the included studies was assessed using the Mixed Method Assessment Tool. In the included studies, various inflammatory markers and gut microbiome diversity and patterns were measured. Sixteen studies met the eligibility criteria and were included in this systematic review. While there were discrepancies in the associations between various inflammatory markers and symptoms, most of the studies showed positive correlations between interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and cancer-related psychoneurological symptoms and gastrointestinal toxicities in gynecologic cancer patients. Although there was no consensus in alpha diversity, studies showed significant dissimilarity in the microbial communities (beta diversity) in patients with gastrointestinal toxicities compared with patients without symptoms or healthy controls. Studies also reported inconsistent findings in the abundance of bacteria at different taxonomic levels. Radiation enteritis-derived microbiota could stimulate TNF-α and interleukin 1 beta (IL-1β) secretion. Alteration of inflammatory markers, the gut microbiome, and their associations show emerging evidence in the development of psychoneurological symptoms and gastrointestinal toxicities in women with gynecologic cancers. More studies on the interactions between the immune system and the gut microbiome, two integral parts of the gut-brain axis, are required to shed light on the roles they play in symptom development.


Chronic electroconvulsive seizures down-regulate expression of the immediate-early genes c-fos and c-jun in rat cerebral cortex.
Acute seizures and other stimuli that increase neuronal activity cause a rapid induction of the immediate-early genes c-fos and c-jun, also referred to as nuclear proto-oncogenes, in the nervous system. In the present study, rats were administered one or more electroconvulsive seizures (ECS) and the responsiveness of c-fos and c-jun to an acute, "test" seizure was examined. Four hours after a single ECS, the induction of c-fos mRNA by a test seizure was blocked, in agreement with earlier findings, but by 18 h the levels of c-fos mRNA could be reinduced by the test seizure, suggesting that 1 day is sufficient to "reset" the responsiveness of this system. However, it was found that chronic, daily ECS treatments resulted in a time-dependent decrease in the expression of c-fos mRNA in response to a test seizure administered 18 h after the last daily ECS; this effect was maximal after 8-10 days of treatment, at which time the induction of c-fos mRNA by the test seizure was blocked dramatically. Chronic ECS also blocked the induction of c-jun in response to an acute, test seizure. The effect of chronic ECS on levels of Fos protein was also investigated. It was found that basal levels of Fos protein were reduced after chronic (10 days) ECS and were not induced by a test seizure. Because levels of Fos protein remain elevated 4 h after a single seizure this finding suggests that the mechanisms by which acute (4 h) and chronic (8-10 days) ECS block the induction of c-fos may differ.


Socioeconomic Status and Clinical Stage of Patients Presenting for Treatment of Chronic Venous Disease.
The association between socioeconomic status (SES) and chronic venous insufficiency has not been rigorously studied. This study aimed to determine the influence of SES on the clinical stage of patients presenting for chronic venous disease therapy. We performed a retrospective study of a prospectively collected data from the Vascular Quality Initiative Varicose Vein Registry at our tertiary referral center. Medical records of patients who underwent therapy for chronic venous disease between January 2015 and June 2019 were queried. SES was quantified using the neighborhood deprivation index (NDI), which summarizes 8 domains of socioeconomic deprivation and is based on census tract data derived from the patients' addresses at the time of the treatment. High NDI scores correspond with lower SES. The association between SES and severity of vein disease at presentation was assessed with bivariate analysis of variance and linear regression analysis. A total of 449 patients with complete SES and clinical-etiology-anatomy-pathophysiology (CEAP) class data were included in the study. The mean age was 58 years, 67% were female, and 60% were White. CEAP classes were distributed as follows C2, 22%; C3, 50%; C4, 15%; C5, 5%; and C6, 8%. Patients with lower SES (higher NDI score) tended to have a higher CEAP class at presentation (P < 0.05). SES was not associated with history of deep venous thrombosis, use of compression therapy, or venous clinical severity score. At our institution, patients with more advanced venous disease tended to belong to a lower SES group. This may reflect that patient with a lower SES have a longer time to presentation due to delay in seeking medical help for venous disease.


[Evaluation of a serum pancreatic tumor marker: the carbohydrate antigen C.A. 19-9].
A radio-immunological assay with monoclonal antibodies was used to measure the C 19-9 antigen in 51 patients to determine its diagnostic value in cancer of the pancreas. The results show that the C 19-9 antigen is a good marker for carcinoma of the pancreas and that it can be commonly used.


A cross-sectional observational study about media and infection control practices: are photographic portrayals of healthcare workers setting a bad example?
Attempts to increase compliance with infection control practices are complex and are - in part - based on attempts to change behaviour. In particular, the behaviour of significant peers (role models) has been shown to be a strong motivator. While role models within the working environment are obviously the most important, some experts suggest that media and public display cannot be ignored. The aim of this present study was to examine the display of technique recommended by current infection control guidelines including the "bare below the elbow" principle, which is considered a basic requirement for good infection control in many countries, in sets of professional stock photos. From 20 random photo-stock websites we selected pictures with search terms "doctor and patient" and "nurse and patient". In all selected photos a doctor or nurse and a patient were presented, healthcare workers (HCWs) were wearing white coats or uniforms, and their arms were visible. Each photo was evaluated with regard to: closure of white coat, sleeve length, personal clothing covered, hairstyle and presence of a wristwatch, bracelet and/or ring. Overall, 1600 photos were evaluated. The most common mistakes were with regard to HCWs' white coats/uniforms. Eighty-nine percent of the photos containing doctor's images were considered incorrect while 28 % of nurse-containing photos were incorrect. The results seem to reflect the real world with only 40 % displaying correct behaviour with doctors being worse than nurses. It seems that the stereotypical image of a doctor does not agree with the current infection control guidelines. If we aim for higher compliance rates of HCWs, we need to change the social image of doctors and improve production, selection and display of stock photo images.


Meningio-angiomatosis in a patient with focal epilepsy: value of PET in diagnoses and preoperative planning of surgery.
A 17-year-old boy with epileptic seizures due to meningio-angiomatosis without neurofibromatosis type 2 is presented. Low grade astrocytoma in the left temporal lobe was resected when he was 11 years old. A recurrence was suspected on following-up MRI and a positive PET scan with 11C-methionine PET 6 years later around the resected area. The language area was mapped using H2(15)O PET activation technique. The lesion was completely resected while preserving the verbal area assisted by three-dimensional imaging protocol of MR-registered PET. The patient was well and seizure-free for 8 years thereafter without antiepileptic drugs. Histologically, there was an increase of dilated arterioles and meningothelial cell-like spindle cells around them, which are characteristic pathological features of meningio-angiomatosis. It is most likely that angiomatous tissue developed perivascular meningiomatous components and formed the meningio-angiomatosis in our presented case. In addition, we presented our protocol of functional neuro-imaging which was useful in terms of the functional neurosurgery.


Trabecular metal™ shoulder prosthesis in the treatment of complex proximal humeral fractures.
Shoulder arthroplasty is one of the options for the treatment of complex proximal humeral fractures. The purpose of this study was to assess the clinical and radiographic results of the trabecular metal shoulder prosthesis in the treatment of complex proximal humeral fractures. Fifty-one consecutive patients with complex proximal humeral fractures who underwent primary shoulder arthroplasties with the trabecular metal™ prosthesis were enrolled in this study. At the final follow-up appointment, 42 of the patients (82.4% of the total patients enrolled) were available for both clinical and radiographic evaluation. There were 28 women and 14 men with a mean age of 65.4 ± 10.7 years. The dominant arm was involved in 30 of the cases. According to Neer's classification, there were seven three-part fractures, 27 four-part fractures and eight head-splitting fractures. Additionally, there were 37 hemiarthroplasties and five total shoulder arthroplasties. After a mean follow-up of 37.0 ± 8.4 months (range 24-52 months), the average ranges of motion were: 38.6 ± 15.0° for external rotation, L3 level for internal rotation and 132.3 ± 36.0° for forward elevation. The mean American Shoulder and Elbow Surgeons, visual analogue scale and University of California, Los Angeles scores were 82.1 ± 14.1, 0.4 ± 1.1 and 28.8 ± 5.1, respectively. The post-operative radiographs exhibited an anatomically attached greater tuberosity in 39 of the 42 shoulders. Of the three patients with greater tuberosity complications, as displayed by their radiographs, two were observed with malpositioned tuberosities, while the other greater tuberosity was resorbed. Proximal migration of the prosthesis was observed in all three shoulders with greater tuberosity complications and in two shoulders with an anatomically attached greater tuberosity. No neurovascular injury, infection or prosthetic loosening was identified during the final follow-up appointments. Satisfactory results can be expected with the trabecular metal shoulder prosthesis for the treatment of complex proximal humeral fractures. The post-operative radiographs demonstrated an anatomically healed greater tuberosity in 93 % of the patients at a minimum follow-up time of two years.


The adhesion of Pseudomonas aeruginosa to high molecular weight human tear film species corresponds to glycoproteins reactive with Sambucus nigra lectin.
Pseudomonas aeruginosa is a pathogen gaining prevalence in contact lens-related corneal ulcers. Tear outflow protects the ocular surface, where high molecular weight tear glycoproteins bind bacteria for removal from the eye. The purpose of the present study was to identify glycoproteins in human tears involved in the adhesion of ocular P. aeruginosa isolates. Basal human tears were applied to a bacterial adhesion assay involving electrophoretic separation of tear components, transfer to nitrocellulose and incubation with biotin-labelled bacteria. Glycoproteins were further characterised using lectin profiling. The results showed large-dimension agarose gels were imperative for the detection of at least four glycoproteins with a migration >200 kDa, including species not previously identified. P. aeruginosa 6294 preferentially bound to a well-defined glycoprotein near the origin of the gel that, unlike other glycoproteins >200 kDa, reacted with Sambucus nigra lectin (sialic acid alpha2-6) but not WGA lectin (N-acetylglucosamine, sialic acid alpha2-3). Adhesion did not involve free biotin label or hydrophobic interactions. Also, the pre-incubation of separated tear glycoproteins with S. nigra lectin increased subsequent adhesion of 6294 to this tear glycoprotein. The less virulent Paer1 strain showed diffuse adhesion in the S. nigra-reactive region at the gel origin. In conclusion, an overlay adhesion assay was developed that identified slow-migrating sialylated glycoprotein species in human tears preferentially bound by P. aeruginosa ocular strains, and S. nigra lectin seemed to enhance the interaction. The study provides a basis for direct investigation of bacterial adhesion to glycoproteins with an apparent migration >200 kDa in tear fluid.


Circulating adhesion molecules in obstructive sleep apnea and cardiovascular disease.
Over 20 years of evidence indicates a strong association between obstructive sleep apnea (OSA) and cardiovascular disease. Although inflammatory processes have been heavily implicated as an important link between the two, the mechanism for this has not been conclusively established. Atherosclerosis may be one of the mechanisms linking OSA to cardiovascular morbidity. This review addresses the role of circulating adhesion molecules in patients with OSA, and how these may be part of the link between cardiovascular disease and OSA. There is evidence for the role of adhesion molecules in cardiovascular disease risk. Some studies, albeit with small sample sizes, also show higher levels of adhesion molecules in patients with OSA compared to controls. There are also studies that show that levels of adhesion molecules diminish with continuous positive airway pressure therapy. Limitations of these studies include small sample sizes, cross-sectional sampling, and inconsistent control for confounding variables known to influence adhesion molecule levels. There are potential novel therapies to reduce circulating adhesion molecules in patients with OSA to diminish cardiovascular disease. Understanding the role of cell adhesion molecules generated in OSA will help elucidate one mechanistic link to cardiovascular disease in patients with OSA.


Analysis of differentially expressed genes between endometrial carcinosarcomas and endometrioid endometrial carcinoma by bioinformatics.
This study aimed to explore the underlying molecular mechanisms of endometrial carcinosarcomas (ECS) and endometrioid endometrial carcinoma (EEC) by bioinformatics analysis. Gene expression profile GSE33723 was downloaded from the Gene Expression Omnibus. A total of 15 ECS and 23 EEC samples were used to identify the differentially expressed genes (DEGs) by significance analysis of microarrays. After construction of protein-protein interaction (PPI) network, Gene Ontology (GO) functional and pathway enrichment analyses of DEGs were performed, followed by network module analysis. A total of 49 DEGs were identified between EEC and ECS samples. In the PPI network, TP53 (tumor protein p53) was selected as the highest degree, hub centrality and betweenness. The top 10 enriched GO terms including regulation of cell death and top 10 significant pathways including cell cycle were selected. After network module analysis, PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1) and AKT2 (v-akt murine thymoma viral oncogene homolog 2) were selected as the co-expressed genes in the states of ECS while STAT3 (signal transducer and activator of transcription 3) and JAZF (JAZF zinc finger 1) were selected as the co-expressed genes in the states of EEC. The DEGs, such as TP53, PIK3R1 and AKT2 may be used for targeted diagnosis and treatment of ECS while STAT3 and JAZF1 may be served as a target for EEC.


The use of ziprasidone in clinical practice: analysis of pharmacokinetic and pharmacodynamic aspects from data of a drug monitoring survey.
This study related clinical effects to daily doses and serum concentrations of ziprasidone by retrospective analysis of data from a therapeutic drug monitoring (TDM) survey established for patients treated with the new antipsychotic drug. In the total sample of 463 patients ziprasidone doses ranged between 20 and 320 mg/d and correlated significantly (r(2)=0.093, P<0.01) with serum concentrations. The latter were highly variable within and between individual patients (between patients median 67 ng/ml, 25-75th percentile 40-103 ng/ml). Pharmacokinetic interactions with comedication played a minor role. According to the clinical global impressions (CGI) scale most of the 348 patients who were under antipsychotic monotherapy with ziprasidone were either much or very much improved (43.3 and 17.3%, respectively). The previously proposed therapeutic range of 50-130 ng/ml ziprasidone in serum or plasma, which can in effect be used interchangeable, was confirmed. In patients who were at least much improved and defined as "responders" mean serum concentrations of ziprasidone were 80 ng/ml and 78 ng/ml in patients who did not reach this improvement score. In patients with serum levels above or below 50 ng/ml, the number of responders was 66 or 63%, respectively. The difference between the two groups was not significant (P=0.375), and improvement or side effects did not correlate significantly (P>0.05) with doses or serum levels. It is concluded that TDM of ziprasidone may be useful for treatment optimization because of highly variable serum concentrations resulting under therapeutically recommended doses of the drug.


Biolistic transfection.
Recent improvements in the biolistic technique and devices have increased its usefulness for transfection of neurons. With these recent advances, both dissociated and slice cultures can be transfected at reasonably high rates. This chapter focuses on the parameters that determine the successful biolistic transfection of neurons in both types of cultures.


Experimental Evaluation of the Effectiveness of Isobornylphenols in the Model of Pathospermia and Their Effect on the Antioxidant-Prooxidant Balance of Male Germ Cells.
We studied the effect of antioxidants dibornol (2,6-diisobornyl-4-methylphenol) and its derivative (4-hydroxymethyl-2,6-diisobornylphenol), members of the alkylated phenols group, on the redox potential of male germ cells and their morphological and functional state in the rat model of pathospermia. Pharmacological effect was observed in animals treated with dibornol. The studied compounds led to the normalization of the antioxidant-prooxidant balance. However, the value of this indicator against the background of treatment with dibornol derivative attested to a shift in the redox balance of cells towards reduction reactions.


IL-33 is induced by amyloid-β stimulation and regulates inflammatory cytokine production in retinal pigment epithelium cells.
Age-related macular degeneration (AMD) is the predominant cause of irreversible blindness in the elderly population. Despite intensive basic and clinical research, its pathogenesis remains unclear. However, evidence suggests that immunological and inflammatory factors contribute to the pathogenesis of AMD. A newly identified cytokine, IL-33, appears to be an important pro-inflammatory cytokine promoting tissue inflammation. In this study, IL-33 was increased through amyloid-beta(1-40) (Aβ(1-40)) stimulation and regulated inflammatory cytokines including IL-6, IL-8, IL-1β, and TNF-α secretion using different signaling pathways in retinal pigment epithelium (RPE) cells. Furthermore, ST2L, the important component of the IL-33 receptor, was significantly increased following recombinant human IL-33 stimulation in RPE cells. These findings suggest that IL-33-mediated inflammatory responses in RPE cells are involved in the pathogenesis of AMD. Greater understanding of the inflammatory effect of IL-33 and its role in RPE cells should aid the development of future clinical therapeutics and enable novel pharmacological approaches towards the prevention of AMD.


Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5.
The GTPase Rab11 plays key roles in receptor recycling, oogenesis, autophagosome formation, and ciliogenesis. However, investigating Rab11 regulation has been hindered by limited molecular detail describing activation by cognate guanine nucleotide exchange factors (GEFs). Here, we present the structure of Rab11 bound to the GEF SH3BP5, along with detailed characterization of Rab-GEF specificity. The structure of SH3BP5 shows a coiled-coil architecture that mediates exchange through a unique Rab-GEF interaction. Furthermore, it reveals a rearrangement of the switch I region of Rab11 compared with solved Rab-GEF structures, with a constrained conformation when bound to SH3BP5. Mutation of switch I provides insights into the molecular determinants that allow for Rab11 selectivity over evolutionarily similar Rab GTPases present on Rab11-positive organelles. Moreover, we show that GEF-deficient mutants of SH3BP5 show greatly decreased Rab11 activation in cellular assays of active Rab11. Overall, our results give molecular insight into Rab11 regulation, and how Rab-GEF specificity is achieved.


Rama midwifery in eastern Nicaragua.
Rama midwives in eastern Nicaragua use a wide array of plants in providing health care to women and infants. In this study, I document the use of medicinal plants by Rama midwives on the island of Rama Cay in eastern Nicaragua. Field investigations included semi-structured interviews and field trips with eight midwives to collect voucher specimens. A total of 162 plant species, in 125 genera and 62 families were documented as useful in midwifery, over 5 years of fieldwork. Most (59%) medicinals are obtained from second-growth forest, and are used to treat more than 35 human ailments. Over 90% have some bioactive principle, most are trees (40%) or herbs (31%), and leaves are the most frequently used plant part. Most herbal remedies are prepared as decoctions and are administered orally. Most midwifery species are wild, but many important species are introduced domesticates native to the NW and OW tropics. This study is important because it is the first systematic study of midwifery in eastern Nicaragua and particularly of Rama midwifery. Eastern Nicaragua is a region undergoing tremendous changes, and the Rama are a people highly acculturated, but with very little documentation of their ethnobotanical heritage. Based on the results of this study I believe that for the near future, the Rama will continue to rely on midwifery as a primary source of health care.


Using enaction to evolve from pre-Covid to post-Covid pedagogy: a case study with South African mathematics teachers.
The Covid-19 pandemic and subsequent national lockdown in South Africa induced a rapid, albeit challenging, implementation of blended learning (with a strong online focus) at all educational levels. During this time, a group of teachers were involved in a specialised computer integrated education course, preparing them for the design and implementation of technologically enhanced modes of teaching. In this research we considered the positive impact of the situation during the pandemic on these mathematics teachers' practice, as well as their conceptualisation of the way forward for technology enhanced mathematics education. We conducted an explorative survey study, employing an enactivist approach, to investigate their experiences of addressing procedural and conceptual aspects of mathematics education, as well as their observations of learners' reactions to these changed practices. Our findings show that participants experienced their exposure to technology as creating an environment they foresee will have a lasting impact on their teaching practice. Participants emphasised the importance of using educational technology meaningfully as a cognitive tool that allows for learners to learn with the technology and not from the technology, which impacts on the importance of learner-centred teaching strategies and the development of high cognitive level interactive learning activities.


Altered backbone and side-chain interactions result in route heterogeneity during the folding of interleukin-1β (IL-1β).
Deletion of the β-bulge trigger-loop results in both a switch in the preferred folding route, from the functional loop packing folding route to barrel closure, as well as conversion of the agonist activity of IL-1β into antagonist activity. Conversely, circular permutations of IL-1β conserve the functional folding route as well as the agonist activity. These two extremes in the folding-functional interplay beg the question of whether mutations in IL-1β would result in changes in the populations of heterogeneous folding routes and the signaling activity. A series of topologically equivalent water-mediated β-strand bridging interactions within the pseudosymmetric β-trefoil fold of IL-1β highlight the backbone water interactions that stabilize the secondary and tertiary structure of the protein. Additionally, conserved aromatic residues lining the central cavity appear to be essential for both stability and folding. Here, we probe these protein backbone-water molecule and side chain-side chain interactions and the role they play in the folding mechanism of this geometrically stressed molecule. We used folding simulations with structure-based models, as well as a series of folding kinetic experiments to examine the effects of the F42W core mutation on the folding landscape of IL-1β. This mutation alters water-mediated backbone interactions essential for maintaining the trefoil fold. Our results clearly indicate that this perturbation in the primary structure alters a structural water interaction and consequently modulates the population of folding routes accessed during folding and signaling activity.


Myocardial recovery from global ischemia and reperfusion: effects of pre- and/or post-ischemic perfusion with low-Ca2+.
The effects of brief (5 min) pre- and/or post-ischemic treatment with low-Ca2+ (10(-4)M) on cardiac mechanical performance during and after increasing periods of total global ischemia were investigated on isolated perfused rat heart. Mechanical parameters studied were changes in diastolic resting length (delta DRL), ventricular contraction amplitude, its first derivative dL/dtmax, and cardiac responsiveness to variations in extracellular Ca2+. The results demonstrate that pre-ischemic low-Ca2+ may completely prevent: (a) the development of myocardial contracture during 45 min ischemia, (b) the occurrence of post-ischemic contracture and (c) a loss in myocardial contractile activity after 30 min of total ischemia. Post-ischemia low-Ca2+ was clearly less effective in protecting the heart against ischemia-induced loss in contractile function and offered no additional benefit when combined with pre-ischemic low-Ca2+. Post-ischemic mechanical recovery appeared to correlate letter with (end-)reperfusion-contracture than with (end-)ischemic contracture. Cardiac responsiveness to perfusate-Ca2+ decreased with increasing duration of the ischemic period (greater than 30 min), but was not significantly altered by the low-Ca2+-treatments. It was concluded from the results that the protective effect of a pre-ischemic low-Ca2+ treatment is superior to that of a similar post-ischemic treatment. The mechanism of protection and the role of Ca2+ in the ischemic process are discussed in terms of changes in the availability of intracellular free-Ca2+.


Volar plate fixation of distal radius fractures.
Volar fixed angle fixation may be considered as the beginning of a new era in restoring wrist function to patients with dorsally displaced distal radius fractures even in the face of comminuted or osteopenic bone. A thorough understanding of the anatomy of the wrist is a prerequisite when volarly approaching dorsally displaced distal radius fractures. The demonstration of the device theoretical and practical advantages requires an appreciation of the basics of working length, principles of plate stability, and the effect of cantilever bending. Volar fixed angle fixation successfully improves wrist function and significantly prevents the complications of the dorsal approach previously intractable to treatment. The current advantages, indications, clinical results, and complications of this new technology are being reviewed.


Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand.
Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1-1 μM) by comparatively low dose of 405 nm light (3.6 J cm(-2)) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin.


Association between serum 25(OH)D and risk of all-cause mortality in adults with prior cardiovascular disease: a cohort study from NHANES 2007-2018.
Serum vitamin D deficiency is common in the patients with cardiovascular disease (CVD), but the association between serum vitamin D levels and risk of all-cause mortality in patients with CVD is controversial. This study aimed to understand better the association between serum 25(OH)D status and risk of all-cause mortality in patients with prior CVD. We conducted a cohort study using data from the National Health and Nutrition Examination Survey from 2007 to 2018 to investigate the association between serum 25(OH)D and the risk of all-cause mortality using multivariate Cox regression models, with further subgroup analyses and interactions smooth curve fitting to address possible nonlinearities. A total of 3220 participants with prior CVD were included in this study, with a total of 930 deaths over a median follow-up of 5.52 years, with multivariable-adjusted serum vitamin D levels after natural log transformation (4.31-4.5 ) as a reference in COX regression, and corrected HRs and 95% CIs of 1.81 (1.31, 2.50), 1.34 (1.07, 1.66), 1.28 (1.05, 1.56),1.00 (reference), 1.10 (0.89, 1.37) for all-cause mortality, respectively. Results remained robust in the stratified analysis of interactions, but a L-shaped relationship was detected. We identified an inflection point of 4.5 after multivariate adjustment through a two-stage linear regression model and recursive algorithm. Our findings demonstrate that increasing serum 25(OH)D levels may have a L-shaped relationship with risk of all-cause mortality and that increases in serum 25(OH)D levels do not continue to reduce the risk of all-cause mortality.


Activation of α7 nicotinic acetylcholine receptor retards the development of endometriosis.
Women with endometriosis have been shown to have a reduced vagal tone as compared with controls and vagotomy promoted while vagus nerve stimulation (VNS) decelerated the progression of endometriosis in mice. Extensive research also has shown that the activation of the cholinergic anti-inflammatory pathway by VNS activates α7 nicotinic acetylcholine receptor (α7nAChR), potently reducing inflammation. Yet whether α7nAChR plays any role in endometriosis is unknown. We evaluated its expression in normal endometrium, ovarian and deep endometriotic lesions, and evaluated its role in the development of endometriosis. Immunohistochemistry analyses of α7nAChR in endometriotic lesions as well as control endometrium, and quantification of tissue fibrosis by Masson trichrome staining were performed. Mouse experiments were conducted to evaluate the impact of α7nAChR activation or suppression on lesional progression and possible therapeutic effect. Finally, in vitro experiments were conducted to evaluate the effect of activation of α7nAChR on epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM) and fibrogenesis in an endometriotic epithelial cell line and primary endometriotic stromal cells derived from ovarian endometrioma tissue samples. Immunostaining of α7nAChR was significantly reduced in human endometriotic epithelial cells as compared with their counterpart in normal endometrium. Lesional α7nAChR staining levels correlated negatively with lesional fibrosis and the severity of dysmenorrhea. The α7nAChR agonist significantly impeded the development of endometriotic lesions in mouse models possibly through hindrance of EMT and FMT. It also demonstrated therapeutic effects in mice with induced deep endometriosis. Treatment of endometriotic epithelial and stromal cells with an α7nAChR agonist significantly abrogated platelet-induced EMT, FMT and SMM, and suppressed cellular contractility and collagen production. α7nAChR is suppressed in endometriotic lesions, and its activation by pharmacological means can impede EMT, FMT, SMM, and fibrogenesis of endometriotic lesions. As such, α7nAChR can be rightfully viewed as a potential target for therapeutic invention. Not applicable.


Label retaining cells in cancer--the dormant root of evil?
The phenomenon of cellular dormancy has been observed in normal adult stem cells in many different tissues such as the skin, the intestine and the hematopoietic system. These dormant cells have been proposed to be important for life-long self-renewal and for the generation of the different cellular lineages. As tumor cells can share properties with normal stem cells, dormant cells might also exist within a tumor. The term tumor dormancy has evolved from the clinical observation in cancer patients that relapse can occur years to decades after apparently successful treatment, suggesting that some cancer cells might resist chemotherapy and persist in a dormant state. Several studies investigating the role of cellular dormancy in normal stem cells and in cancer hint towards a complex network involving different pools of cells. These cells might interact with each other or even dynamically switch their phenotypes dependent upon so far unknown endogenous and microenvironmental stimuli. In this review, we will discuss the recent findings related to cellular dormancy in normal adult stem cells and in cancer. Furthermore, the clinical relevance of dormancy and its dynamic regulation in tumor cells will be highlighted.


Molecular therapies for tuberous sclerosis and neurofibromatosis.
Neurofibromatosis type 1 (NF1) and tuberous sclerosis complex (TSC) are autosomal-dominant genetic disorders that result from dysregulation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. NF1 is caused by mutations in the NF1 gene on chromosome 17q11.2. Its protein product, neurofibromin, functions as a tumor suppressor and ultimately produces constitutive upregulation of mTOR. TSC is caused by mutations in either the TSC1 (chromosome 9q34) or TSC2 (chromosome 16p.13.3) genes. Their protein products, hamartin and tuberin, respectively, form a dimer that acts via the GAP protein Rheb (Ras homolog enhanced in brain) to directly inhibit mTOR, again resulting in upregulation. Specific inhibitors of mTOR are in clinical use, including sirolimus, everolimus, temsirolimus, and deforolimus. Everolimus has been shown to reduce the volume and appearance of subependymal giant cell astrocytomas (SEGA), facial angiofibromas, and renal angiomyolipomas associated with TSC, with a recent FDA approval for SEGA not suitable for surgical resection. This article reviews the use of mTOR inhibitors in these diseases, which have the potential to be a disease-modifying therapy in these and other conditions.


Differential expression of glutathione S-transferase isoenzymes in murine small intestine and colon.
Glutathione (GSH) S-transferase (GST) isoenzymes of the small intestine and colon of female A/J mice have been purified and characterized to determine their interrelationships with other murine GSTs. Cytosolic GST activity in the small intestine was at least due to six isoenzymes with isoelectric points (pI) of 9.5, 9.3, 9.1, 8.5, 6.2 and 5.5. Small intestine isoenzymes with pI values of 9.5, 9.3, 8.5, and 6.2 were identical to the mGSTA1-1 (Alpha class), mGSTP1-1 (Pi class), mGSTM1-1 (Mu class) and mGSTA4-4 (Alpha class), respectively, of other A/J mouse tissues on the basis of their reverse-phase HPLC elution profile, immunological cross-reactivity and/or N-terminal region amino acid sequence. Even though GST9.1 of the small intestine cross-reacted with the antibodies raised against Pi class GST, reverse-phase HPLC and N-terminal amino acid sequence analyses suggested that this isoenzyme may be structurally different from mGSTP1-1 as well as mGSTP2-2. Likewise, despite immunological similarity with the Mu class GSTs, small intestine GST5.5 appeared to be different from other Mu class murine GSTs characterized previously. Cytosolic GST activity in the colon was mainly due to four isoenzymes with pI values of 9.8, 9.4, 6.6 and 5.8. While the identity of colon GST6.6 could not be established due to its low abundance, GST9.8, GST9.4 and GST5.8 were identical to mGSTP1-1, mGSTM1-1 and mGSTA4-4, respectively, of other A/J mouse tissues including the small intestine. Isoenzymes corresponding to small intestine GST9.1 and GST5.5 could not be detected in the colon. The results of the present study indicate that the small intestine of female A/J mice is better equipped for protection against toxic effects of electrophiles than colon.


Development of a MALDI-TOF MS strategy for the high-throughput analysis of biomarkers: on-target aptamer immobilization and laser-accelerated proteolysis.
An aptamer-based strategy was developed for the high-throughput analysis of protein biomarkers, such as lysozyme, by on-target MALDI-TOF MS. The aptamers were immobilized on the target plate through formation of covalent bonds with a stable and porous gold layer. An infrared laser was subsequently applied for fast proteolysis. High sensitivities were observed both in standard solutions and human urine.


Endoplasmic reticulum stress intolerance in EIF2B3 mutant oligodendrocytes is modulated by depressed autophagy.
Eukaryotic translation initiation factor 2B (eIF2B) is an essential factor for the initiation of protein synthesis. Mutations in eIF2B encoded by EIF2B1-5 cause a lethal leukoencephalopathy--vanishing white matter disease (VWM). Previous studies have suggested that an improper activated unfolded protein response (UPR) after endoplasmic reticulum stress (ERS) contributed to the pathogenesis of the disease. Autophagy, an important compensatory pathway after ERS, was analyzed in this study. To determine the tolerance differences to ERS, cell viability and apoptosis rates were detected in oligodendrocyte cell lines transfected with EIF2B3-c.1037T>C or the wild type. Autophagy flux was measured between groups. Autophagy inducers and inhibitors were used to identify the role of autophagy in the mutant oligodendrocytes. We confirmed that oligodendrocytes with mutant EIF2B3 was less tolerant to ERS than the wild type, with decreased cell viability and increased apoptosis rates. Autophagy flux was depressed in mutant oligodendrocytes under baseline condition and after ERS stimulation. Reduced expression of autophagy related gene (Atg) 3 and Atg 7 were involved in the depression of autophagy flux. The mutant oligodendrocytes pretreated with autophagy inducers showed stable cell viability and decreased apoptosis despite ERS induction, whereas the autophagy inhibitors aggravated cell apoptosis and viability declination. Oligodendrocytes transfected with mutant EIF2B3 was less tolerant to ERS than the wild type. Depressed autophagy flux was observed in the mutant cells at baseline and after ERS stimulation. Improperly depressed autophagy played a role in the susceptibility to ERS in EIF2B3 mutant oligodendrocytes.


Ranolazine and Vernakalant Prevent Ventricular Arrhythmias in an Experimental Whole-Heart Model of Short QT Syndrome.
Ranolazine has been reported to have an antiarrhythmic potential. The aim of this study was to assess the electrophysiologic effects of ranolazine and to compare its effects to vernakalant in an experimental whole-heart model of short-QT syndrome. Rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IKATP channel opener, was administered (1 μM). Endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (- 34 milliseconds, P < 0.05) and action potential duration (APD90 ; - 31 milliseconds, P < 0.05). This was accompanied by a reduction of effective refractory period (ERP; - 32 milliseconds, P < 0.05). Subsequently, hearts were additionally perfused with ranolazine (10 μM, n = 12) or vernakalant (10 μM, n = 14). Ranolazine led to an increase of QT-interval (+ 29 milliseconds, P < 0.05), APD90 (+ 18 milliseconds, P < 0.05) and ERP (+ 28 milliseconds, P < 0.05) as compared with sole pinacidil treatment. Similar results were observed under the influence of vernakalant (APD90: + 25 milliseconds, QT-interval: + 34 milliseconds, ERP: + 31 milliseconds). Under the influence of pinacidil, ventricular fibrillation (VF) was inducible by a standardized pacing protocol including programmed stimulation and aggressive burst stimulation in 8 of 12 hearts (ranolazine group, 34 episodes) and 7 of 14 hearts (vernakalant group, 24 episodes). Additional infusion of ranolazine (1 of 12 hearts, 1 episode) or vernakalant (1 of 14 hearts, 3 episodes) led to a significant suppression of VF. In the present pharmacologic model of short QT syndrome treatment with pinacidil led to an increased inducibility of VF in association with a reduction in ERP. Additional treatment with ranolazine or vernakalant reversed this effect and demonstrated potent antiarrhythmic properties based on an increase of ERP.


Spectroscopy and upconversion of Dy3+ doped in sodium zinc phosphate glass.
Optical absorption and fluorescence spectra of Dy3+ doped in sodium zinc phosphate glasses have been reported. Judd-Ofelt theory has been applied to analyze the spectra and determine the optical parameters such as transition probabilities, radiative lifetime, stimulated emission cross-section, etc. The fluorescence intensity of Dy3+ corresponding to 4F9/2-->6H13/2 transition increases with increasing concentration of Dy3+ but at higher concentrations, concentration quenching is observed. The radiative lifetime of the 4F9/2 level at 1 mol% concentration of Dy3+ in this host is found to be 541 micros. Emission corresponding to 4F9/2-->6H13/2 transition (570 nm) is observed on excitation with NIR radiation due to upconversion. An attempt is made to explain this observation.


Acute heat stress up-regulates neuropeptide Y precursor mRNA expression and alters brain and plasma concentrations of free amino acids in chicks.
Heat stress causes an increase in body temperature and reduced food intake in chickens. Several neuropeptides and amino acids play a vital role in the regulation of food intake. However, the responses of neuropeptides and amino acids to heat-stress-induced food-intake regulation are poorly understood. In the current study, the hypothalamic mRNA expression of some neuropeptides related to food intake and the content of free amino acids in the brain and plasma was examined in 14-day-old chicks exposed to a high ambient temperature (HT; 40±1 °C for 2 or 5 h) or to a control thermoneutral temperature (CT; 30±1 °C). HT significantly increased rectal temperature and plasma corticosterone level and suppressed food intake. HT also increased the expression of neuropeptide Y (NPY) and agouti-signaling protein (ASIP) precursor mRNA, while no change was observed in pro-opiomelanocortin, cholecystokinin, ghrelin, or corticotropin-releasing hormone precursor mRNA. It was further found that the diencephalic content of free amino acids - namely, tryptophan, leucine, isoleucine, valine and serine - was significantly higher in HT chicks with some alterations in their plasma amino acids in comparison with CT chicks. The induction of NPY and ASIP expression and the alteration of some free amino acids during HT suggest that these changes can be the results or causes the suppression of food intake.


Retentive properties of a new post and core system.
Fifty Flexi-Posts were cemented in extracted teeth and tested for tensile strength. The Flexi-Post was the most retentive post tested when compared with posts used in a similar study. The retention of the Flexi-Post became greater as the size of the post increased.


The effect of N-(methoxy polyethylene glycol) rho-hydroxymercuribenzamide, a polymeric sulfhydryl group reagent, on spermatozoan motility.
The water-soluble, polymeric sulfhydryl group reagent N-(methoxypolyethylene glycol) rho-hydroxymercuribenzamide (Mw 5000) inhibited the motility of human spermatozoa. Its activity profile was very similar to that of rho-hydroxymercuribenzene sulfonate, a charged sulfhydryl group reagent that is a very poor membrane penetrant. These results suggest that functional sulfhydryl groups of the spermatozoan membrane are easily accessible and externally oriented on the membrane surface.


Acute thrombocytopenia: an unusual complication occurring after drug-eluting microspheres transcatheter hepatic chemoembolization.
Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.


Home-based exercises during the COVID-19 quarantine situation for office workers: A commentary.
Staying at home for the prevention of COVID-19 is an accepted fact. Office workers are a group of people, who had to wake up early in the morning and at least had a fixed pattern of sleeping and working. In this situation, complaints about the neck, shoulder and lower back tend to increase and this is a good time to learn and do some practical exercises at home. This letter presents some of the home-based exercise notes for prevention of musculoskeletal disorders among office workers, following the guidelines prepared by the American College of Sports Medicine.


Inorganic phosphate has a crucial effect on Cry3Aa delta-endotoxin production.
The study aimed at increasing Cry3Aa delta-endotoxin production by a local isolate of Bacillus thuringiensis (B.t. strain Mm2). To this end, different nutritional conditions were tested for their effects on Cry3Aa yields. Bacillus thuringiensis Mm2 was grown by shaking at 30 degrees C in different media. Samples were taken from the cultures at intervals and used for protein extraction. SDS-PAGE was performed for toxin analysis. Inclusion of inorganic phosphate (Pi) into the Difco's sporulation medium at an increased level of 200 mmol l-1 caused a fivefold increase (from 3 to 15.6 microg ml-1) in toxin production. Omission of FeSO4 from the medium decreased this yield by half. Resuspension experiments suggested catabolite repression of toxin biosynthesis by glucose. The inclusion of high Pi invariably increased toxin synthesis, even in the absence of sugars. Inorganic phosphate had the most striking effect on toxin biosynthesis. Iron effect was found to be unique to our isolate whereas Pi effect seemed to be common to the biosynthesis of Cry3Aa-type toxins. Stimulation of toxin synthesis by Pi did not seem to represent a relief from glucose repression. Bacillus thuringiensis is the most versatile biopesticide for use in pest management. Regarding cost-effectiveness of related fermentations, high Pi supplement drastically increases Coleoptera-specific toxin synthesis.


High Curie temperature ferromagnetic structures of (Sb2Te3)1-x(MnSb2Te4)x with x = 0.7-0.8.
Magnetic topological materials are promising for realizing novel quantum physical phenomena. Among these, bulk Mn-rich MnSb2Te4 is ferromagnetic due to MnSb antisites and has relatively high Curie temperatures (TC), which is attractive for technological applications. We have previously reported the growth of materials with the formula (Sb2Te3)1-x(MnSb2Te4)x, where x varies between 0 and 1. Here we report on their magnetic and transport properties. We show that the samples are divided into three groups based on the value of x (or the percent septuple layers within the crystals) and their corresponding TC values. Samples that contain x < 0.7 or x > 0.9 have a single TC value of 15-20 K and 20-30 K, respectively, while samples with 0.7 < x < 0.8 exhibit two TC values, one (TC1) at ~ 25 K and the second (TC2) reaching values above 80 K, almost twice as high as any reported value to date for these types of materials. Structural analysis shows that samples with 0.7 < x < 0.8 have large regions of only SLs, while other regions have isolated QLs embedded within the SL lattice. We propose that the SL regions give rise to a TC1 of ~ 20 to 30 K, and regions with isolated QLs are responsible for the higher TC2 values. Our results have important implications for the design of magnetic topological materials having enhanced properties.


Dietary phytoestrogen diosgenin interrupts metabolism, physiology, and reproduction of Swiss albino mice: Possible mode of action as an emerging environmental contaminant, endocrine disruptor and reproductive toxicant.
Dietary phytoestrogens are the main source of environmental contamination due to their estrogen-mimicking and endocrine-disrupting effects, posing a threat to microbial, soil, plant, and animal health. Diosgenin, a phytosteroid saponin, is used in many traditional medicines, nutraceuticals, dietary supplements, contraceptives, and hormone replacement therapies against numerous diseases and disorders. It is important to be aware of the potential risks associated with diosgenin, as well as its potential to cause reproductive and endocrine toxicity. Due to the lack of research on the safety and probable adverse side effects of diosgenin, this work evaluated the endocrine-disrupting and reproductive toxicity of diosgenin in albino mice by following acute toxicity (OECD-423), repeated dose 90-day oral toxicity (OECD-468), and F1 extended one-generation reproductive toxicity (OECD-443) studies. Diosgenin was found to be slightly toxic, with LD50 for male and female mice being 546.26 and 538.72 mg/kg, respectively. Chronic exposure of diosgenin (10, 50, 100, and 200 mg/kg) generated oxidative stress, depleted antioxidant enzymes, disturbed homeostasis of the reproductive hormones, and interrupted steroidogenesis, germ cell apoptosis, gametogenesis, sperm quality, estrous cycle, and reproductive performance in the F0 and F1 offspring. Long-term oral exposure of diosgenin to the mice disturbed the endocrine and reproductive functions and generated transgenerational reproductive toxic effects in F0 and F1 offspring. These results suggest that diosgenin should be used carefully in food products and medical applications due to its potential endocrine-disrupting and reproductive toxic effects. The findings of this study provide a better understanding of the potential adverse effects of diosgenin and the need for appropriate risk assessment and management of its use.


Stereotactic body radiation therapy in hepatocellular carcinoma and cirrhosis: evaluation of radiological and pathological response.
Loco-regional therapies for cirrhotic patients with hepatocellular carcinoma (HCC) who are awaiting liver transplantation (OLT) attempt to prevent tumor progression. However, there is limited data regarding the efficacy of stereotactic body radiation therapy (SBRT) as loco-regional treatment. From 2006 to 2009, 27 HCC patients (AJCC I, II) listed for OLT underwent SBRT. Thirty-nine lesions were treated and 27 assessed radiologically. Seventeen patients had OLT, liver explants were analyzed and 22 lesions underwent pathological evaluation. In a cumulative analysis of all imaging, 30% had complete response, 7% had partial response, 56% were stable, and 7% had progression of disease. Of the 22 pathologically evaluated lesions, 37% were responders: 14% with complete response, 23% with partial response, and 63% with no response. Side effects from SBRT were recorded in three patients, which included nausea in two and liver decompensation in one. SBRT achieves total or partial radiological response in 37% of patients and total or partial pathological response in 37% of patients with early HCC in the setting of cirrhosis. SBRT may be a safe and effective alternative for local tumor control in patients with HCC and cirrhosis awaiting OLT.


The Budd-Chiari syndrome in pregnancy.
A case of Budd-Chiari syndrome in a young woman, which started probably in the last trimester of pregnancy, is described. The diagnosis was made clinically and was confirmed by inferior venacavography and on exploratory laparotomy. The possible connection of the syndrome with the pregnancy is discussed.


Clinical and ultrastructural correlations in nasal mucociliary function observed in children with recurrent airways infections.
A study was made of 106 children between 1 and 15 years of age (mean 6 years) with recurrent upper and lower airways infections since birth. Nasal mucociliary transport (NMT) velocity was determined in all subjects by the Tc99m-labeled seroalbumin technique. In 42 children, NMT was found to be altered. In this group of patients the technique was repeated in a period of between 1 and 2 years later. In 23 cases (55%) transport had normalized, while in 19 (45%) it remained altered. Recurrent pneumonia and constant rhinorrhea were more frequent in this group. Situs inversus was only detected in 2 of these patients. Pathology showed ciliary ultrastructure, the absence of dynein arms and microtubule alterations. The absence of cilia was observed in some patients. Normal cilia were also encountered in children with persistently altered nasal mucociliary transport.


Arteriography and chemotherapy in localized trophoblastic disease, by means of local- (pelvic-) intraarterial infusion.
In spite of considerable progress in systemic chemotherapy in malignant throphoblastic disease, there remains a small group of patients who fail to respond to this type of therapy. Here the trophoblastic process may be localized by means of an arteriography, and treated by a local, intraarterial infusion of cytotoxic compounds in high concentration. The latter makes possible the treatment of processes localized in essential organs which are hard to remove, as well as in young women wishing to preserve their reproductive capacity. Our experiences is limited to one case of a young woman with chorioadenoma destruens in the uterus, resistant to systemic chemotherapy, yet successfully treated with pelvic, intraarterial infusion of cytotoxics.


Strategic Interventions in the Management of Gestational Diabetes to Reduce Type 2 Diabetes Mellitus in Women in Malaysia.
No abstract available.


Immunostimulant Complexed With Polylysine Limits Transport and Maintains Immune Cell Activation.
Activation of the immune system to treat cancer has emerged as a powerful therapy tool, however, treatments must overcome the immunosuppressive microenvironment established by tumors. Toll-like receptor (TLR) agonists like CpG and polyI:C are potent stimulators of non-specific, pro-inflammatory immune responses, targeting TLR9 and TLR3, respectively. While these immunostimulants seem promising, systemic exposure can eventually induce severe side effects. Adverse inflammatory reactions in healthy tissues may be avoided by delivering and retaining immunostimulants in proximity to tumors or to primary sites of tumor metastases. Immunostimulants such as CpG and polyI:C cannot be completely immobilized, however, since the target TLR9 and TLR3 are located intracellularly. Previously, polycations like poly-l-lysine (PLL) have been complexed to the anionic CpG or polyI:C with the purpose of improving intracellular delivery and potency. Here, the relationship between PLL molecular weight and immunostimulant complexation, TLR activation, and transport in a simple, model tumor microenvironment was investigated. The polyplexes could be formulated to dramatically limit immunostimulant transport suggesting the potential for injection site retention and minimized systemic exposure of immunostimulants. The molecular weight of PLL and ratio of PLL to immunostimulant affected the accessibility of the immunostimulant within the polyplex and polyplex interaction strength.


The face inversion effect in non-human primates revisited - an investigation in chimpanzees (Pan troglodytes).
Faces presented upside-down are harder to recognize than presented right-side up, an effect known as the face inversion effect. With inversion the perceptual processing of the spatial relationship among facial parts is disrupted. Previous literature indicates a face inversion effect in chimpanzees toward familiar and conspecific faces. Although these results are not inconsistent with findings from humans they have some controversy in their methodology. Here, we employed a delayed matching-to-sample task to test captive chimpanzees on discriminating chimpanzee and human faces. Their performances were deteriorated by inversion. More importantly, the discrimination deterioration was systematically different between the two age groups of chimpanzee participants, i.e. young chimpanzees showed a stronger inversion effect for chimpanzee than for human faces, while old chimpanzees showed a stronger inversion effect for human than for chimpanzee faces. We conclude that the face inversion effect in chimpanzees is modulated by the level of expertise of face processing.


Isolation and functional characterization of primary endothelial cells from mouse cerebral cortex.
Endothelial cells (ECs) lining blood vessels are implicated in organ development, function, and maintenance. We present a detailed protocol enabling isolation and characterization of primary mouse brain ECs, including quality controls and functional assays. These procedures promote survival of primary brain ECs for the assessment of endothelial health. Since alterations in brain ECs are involved in the onset and progression of neurological disorders, this protocol represents a valuable tool to better understand the roles of ECs in brain health. For complete details on the use and execution of this profile, please refer to Ouellette et al. (2020).


Electrochemical corrosion behavior and elasticity properties of Ti-6Al-xFe alloys for biomedical applications.
The present study is to investigate the microstructural characteristics, electrochemical corrosion behavior and elasticity properties of Ti-6Al-xFe alloys with Fe addition for biomedical application, and Ti-6Al-4V alloy with two-phase (α+β) microstructure is also studied as a comparison. Microstructural characterization reveals that the phase and crystal structure are sensitive to the Fe content. Ti-6Al alloy displays feather-like hexagonal α phase, and Ti-6Al-1Fe exhibits coarse lath structure of hexagonal α phase and a small amount of β phase. Ti-6Al-2Fe and Ti-6Al-4Fe alloys are dominated by elongated, equiaxed α phase and retained β phase, but the size of α phase particle in Ti-6Al-4Fe alloy is much smaller than that in Ti-6Al-2Fe alloy. The corrosion resistance of these alloys is determined in SBF solution at 37 °C. It is found that the alloys spontaneously form a passive oxide film on their surface after immersion for 500 s, and then they are stable for polarizations up to 0 VSCE. In comparison with Ti-6Al and Ti-6Al-4V alloys, Ti-6Al-xFe alloys exhibit better corrosion resistance with lower anodic current densities, larger polarization resistances and higher open-circuit potentials. The passive layers show stable characteristics, and the wide frequency ranges displaying capacitive characteristics occur for high iron contents. Elasticity experiments are performed to evaluate the elasticity property at room temperature. Ti-6Al-4Fe alloy has the lowest Young's modulus (112 GPa) and exhibits the highest strength/modulus ratios as large as 8.6, which is similar to that of c.p. Ti (8.5). These characteristics of Ti-6Al-xFe alloys form the basis of a great potential to be used as biomedical implantation materials.


Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study.
The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of bortezomib plus docetaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Forty-eight patients received up to eight 21-day cycles of docetaxel (60-100 mg m(-2) on day 1) plus bortezomib (1.0-1.5 mg m(-2) on days 1, 4, 8, and 11). Pharmacodynamic and pharmacokinetic analyses were performed in a subset of patients. Five patients experienced DLTs: grade 3 bone pain (n=1) and febrile neutropenia (n=4). The MTD was bortezomib 1.5 mg m(-2) plus docetaxel 75 mg m(-2). All 48 patients were assessable for safety and efficacy. The most common adverse events were diarrhoea, nausea, alopecia, asthenia, and vomiting. The most common grade 3/4 toxicities were neutropenia (44%), and febrile neutropenia and diarrhoea (each 19%). Overall patient response rate was 29%. Median time to progression was 5.4 months. In patients with confirmed response, median time to response was 1.3 months and median duration of response was 3.2 months. At the MTD, response rate was 38%. Pharmacokinetic characteristics of bortezomib/docetaxel were comparable with single-agent data. Addition of docetaxel appeared not to affect bortezomib inhibition of 20S proteasome activity. Mean alpha-1 acid glycoprotein concentrations increased from baseline at nearly all time points across different bortezomib dose levels. Bortezomib plus docetaxel is an active combination for anthracycline-pretreated advanced/metastatic breast cancer. The safety profile is manageable and consistent with the side effects of the individual agents.


The association between obstructive sleep apnea and stroke in sickle-cell disease children.
The prevalence of stroke in SCD patients was reported to be around 4%; however, the pediatric category was among the higher risk group for stroke compared to young and middle age adults. Furthermore, the risk of OSA increases in SCD children. The objective of this study is to calculate the prevalence of stroke in children with SCD with and without obstructive sleep apnea. This is a cross-sectional study held at two major tertiary hospitals in Jeddah, Saudi Arabia. Inclusion criteria included patients aged between 2 and 18 at the time of enrollment with confirmed SCD. The primary outcome of the study was at least one documented episode of stroke over the last 3 years. OSA was assessed using PSQ. A total of 150 children with SCD were included in the study. The mean age was 9.6 (±4.3). Most of the sample (85.3%) were sickle-cell anemia with HbSS. Children who were positive for OSA were at higher odds of having a stroke [OR 2.97; 95% CI 1.13-7.75 (P = 0.02)]. The relationship between OSA and stroke was not significant in the multivariant analysis. Patients who had OSA had a higher prevalence of stroke compared to non-OSA patients by 16% with almost three times higher odds. The difference was statistically significant in bivariant but not multivariant analysis. The rate of hospitalization, emergency visit, and blood transfusion were not affected by OSA status. Screening for OSA in high-risk patients such as SCD children and early management could prevent the risk of SCD complications.


Osmotic Dilator Intra-Abdominal Perforation: A Case Report.
This report describes an unusual case of a retained hygroscopic osmotic dilator following second trimester dilation and evacuation. A 24-year-old woman presented for elective pregnancy termination at 16 weeks gestational age. A cervical osmotic dilator could not be retrieved and fractured on attempted removal. Magnetic resonance imaging showed perforation through the cervix, possibly traversing the peritoneum. Hysteroscopy and laparoscopy were performed to remove the retained dilator. Significant inflammation and mesenteric adhesions surrounded the osmotic dilator, which was successfully removed. This is the first reported case of an intra-abdominal osmotic dilator. Although this device is inert, close follow-up and timely retrieval, possibly with hysteroscopy or laparoscopy, are recommended to minimize the resulting inflammatory response.


Arthroscopic removal of entrapped debris following dislocation of a total hip arthroplasty.
The entrapment of a foreign body within a dislocated hip prosthesis is an unusual occurrence. Dislodgement of the fragments by closed reduction should be attempted to try to extricate the fragment from the femoral head and acetabular cup interface. If closed techniques prove unsuccessful, arthroscopy can be used to guide instrumented removal of the interposed fragments.