[The study of psychotherapy. Analysis of the psychotherapies given in an ambulatory psychiatric service].
Using critisized statistical technics, the authors have studied the psychotherapies done at a given time in a university psychiatric outpatient clinic. Thereupon they display some correlations, more specifically, the importance of sex gender, of patients' socio-cultural level, of unconscious socio-cultural stereotypes present in the therapists, of diagnosis and of the motivation to seek treatment by psychotherapy. Statistical analysis allows a more coherent approach of these problems.


Development and validation of a highly sensitive and specific electrochemical assay to quantify anti-SARS-CoV-2 IgG antibodies to facilitate pandemic surveillance and monitoring of vaccine response.
Amperial™ is a novel assay platform that uses immobilized antigen in a conductive polymer gel followed by an electrochemical detection. A highly specific and sensitive assay was developed to quantify levels of IgG antibodies to SARS-CoV-2 in saliva. After establishing linearity and limit of detection we established a reference range of 5 standard deviations above the mean. There were no false positives in 667 consecutive saliva samples obtained prior to 2019. Saliva was obtained from 34 patients who had recovered from documented COVID-19 or had documented positive serologies. All of the patients with symptoms severe enough to seek medical attention had positive antibody tests and 88% overall had positive results. We obtained blinded paired saliva and plasma samples from 14 individuals. The plasma was analyzed using an EUA-FDA cleared ELISA kit and the saliva was analyzed by our Amperial™ assay. All 5 samples with negative plasma titers were negative in saliva testing. Eight of the 9 positive plasma samples were positive in saliva and 1 had borderline results. A CLIA validation was performed as a laboratory developed test in a high complexity laboratory. A quantitative non-invasive saliva based SARSCoV-2 antibody test was developed and validated with sufficient specificity to be useful for population-based monitoring and monitoring of individuals following vaccination.


Is bisphosphonate use a risk factor for atypical periprosthetic/peri-implant fractures? - A metanalysis of retrospective cohort studies and systematic review of the current evidence.
Atypical periprosthetic/peri-implant fractures are not recognised in any widely used classification and therefore little focus is given to them. Multiple case reports and case series demonstrate these fractures exist and are related to bisphosphonate (BP) use. Are patients taking long-term BPs at an increased risk of developing an atypical periprosthetic/peri-implant fracture? Is a particular BP drug causing an increased risk of fracture? Is there a correlation between the time of BP use and the incidence of fractures? Do vitamin D analogues or parathyroid hormones reduce the time to union? Systematic review of all available evidence on the existence of periprosthetic/peri-implant atypical fractures in patients taking long-term BPs and metanalysis of available retrospective cohort studies. Selected 1 systematic review, 7 retrospective cohort studies (5 used for metanalysis) and 32 case reports. Metanalysis reported a risk ratio of 14.1, p=0.25, suggesting bisphosphonates are a risk factor in the development of periprosthetic/peri-implant atypical fractures. The secondary outcomes couldn't be reliably identified due to the small size of available studies and risk of significant bias. Atypical periprosthetic/peri-implant fractures are an entity and seem to be associated with the use of bisphosphonates. The benefits of bisphosphonates use outweigh the risks, but clinicians should be aware of atypical fractures and actively search for them when patients on long-term bisphosphonates attend with non-specific pain close to the implant/prosthesis or reduced mobility. II, Systematic review and metanalysis.


Absorption of contrast medium during ERCP.
In order to assess systemic absorption, serum diatrizoate levels were measured in 25 patients requiring endoscopic retrograde cholangiopancreatography (ERCP). Urinary diatrizoate was measured in the urine of seven of these. In five additional patients, diatrizoate was instilled into the duodenum during endoscopy. Blood was drawn before and after completion of the procedure in all patients and at intervals from 2 to 24 hr in nine. Eighteen-hour urine collections were obtained from seven patients. Increases in serum diatrizoate concentration were 7.10 micrograms/ml +/- 3.01 (mean +/- SE) in the duodenal-instillation patients, 230.68 +/- 53.24 micrograms/ml in 9 patients in whom only the pancreatic duct was visualized, 7.83 +/- 1.05 micrograms/ml in three patients in whom only the bile duct was visualized, and 77.67 +/- 28.22 micrograms/ml in 13 patients in whom both ducts were visualized. The mean total urinary excretion of diatrizoate was 3.05 +/- 0.98 g of diatrizoate. Endoscopists performing ERCP should be aware of the likelihood of systemic absorption and the possibility of reactions to iodinated contrast materials in sensitive patients.


Relationship between genetic polymorphisms of cytokines and self-reported sleep complaints and habitual caffeine consumption.
Pro-inflammatory cytokines are involved in sleep-wake regulation and are associated with caffeine consumption. This is a cross-sectional study in 1023 active French workers investigating associations between self-reported sleep complaints (>3months) and total sleep time (TST) with nine single-nucleotide-polymorphisms (SNPs) including pro-inflammatory cytokines, according to caffeine consumption. Participants were characterized as low, moderate and high (0-50, 51-300, and >300 mg/day) caffeine consumers. After adjusting the odd ratios (OR) for age, gender, and smoking, the risk of sleep complaints was higher in subjects with genetic mutations in tumor necrosis factor alpha (TNF-α, rs 1800629) (ORa [95%CI] = 1.43 [1.07-1.92] for both G/A and A/A aggregate genotypes) or interleukin-1 beta (IL-1β, rs1143627) (ORa = 1.61 [1.08-2.44] for homozygous A/A genotype), and the risk was higher when subjects carry the mutations in TNF-α plus IL-1β regardless of caffeine consumption. When stratified with caffeine consumption, the risk of sleep complaints was higher in TNF-α A allele carriers in high caffeine consumers, and in homozygous A/A genotype of IL-1β in moderate and high consumers. None of the nine SNPs influence TST, with the exception of the mutation on CYP1A2 and only when stratified with caffeine consumption. Our results also indicated more caffeine side-effects when carrying mutation on IL1β. This study showed that polymorphisms in TNF-α and/or IL-1β influenced sleep complaints but did not influence total sleep time. This suggests that management of sleep complaints, which can be addressed by clinical interventions, should consider the influence of the genetic profile of pro-inflammatory cytokines.


Sex-dependent changes in metabolism and behavior, as well as reduced anxiety after eliminating ventromedial hypothalamus excitatory output.
The ventromedial hypothalamic nucleus (VMH) regulates energy homeostasis as well as social and emotional behaviors. Nearly all VMH neurons, including those in the sexually dimorphic ventrolateral VMH (VMHvl) subregion, release the excitatory neurotransmitter glutamate and use the vesicular glutamate transporter 2 (Vglut2). Here, we asked how glutamatergic signaling contributes to the collective metabolic and behavioral responses attributed to the VMH and VMHvl. Using Sf1-Cre and a Vglut2 floxed allele, Vglut2 was knocked-out in SF-1 VMH neurons (Vglut2 (Sf1-Cre) ). Metabolic and neurobehavioral assays were carried out initially on Vglut2 (fl/fl) and Vglut2 (Sf1-Cre) mice in a mixed, and then in the C57BL/6 genetic background, which is prone to hyperglycemia and diet induced obesity (DIO). Several phenotypes observed in Vglut2 (Sf1-Cre) mice were largely unexpected based on prior studies that have perturbed VMH development or VMH glutamate signaling. In our hands, Vglut2 (Sf1-Cre) mice failed to exhibit the anticipated increase in body weight after high fat diet (HFD) or the impaired glucose homeostasis after fasting. Instead, there was a significant sex-dependent attenuation of DIO in Vglut2 (Sf1-Cre) females. Vglut2 (Sf1-Cre) males also display a sex-specific loss of conditioned-fear responses and aggression accompanied by more novelty-associated locomotion. Finally, unlike the higher anxiety noted in Sf1 (Nestin-Cre) mice that lack a fully formed VMH, both male and female Vglut2 (Sf1-Cre) mice were less anxious. Loss of VMH glutamatergic signaling sharply decreased DIO in females, attenuated aggression and learned fear in males, and was anxiolytic in males and females. Collectively, our findings demonstrate that while glutamatergic output from the VMH appears largely dispensable for counter regulatory responses to hypoglycemia, it drives sex-dependent differences in metabolism and social behaviors and is essential for adaptive responses to anxiety-provoking stimuli in both sexes.


[Effect of Intolerance of Uncertainty on Fear of Childbirth in Primiparas : A Moderated Mediating Model].
To explore the mediating effect of childbirth self-efficacy on the impact pathway of intolerance of uncertainty on the fear of childbirth in primiparas in the second and third trimesters and the potential moderating effect of perceived partner responsiveness. A total of 429 primiparas in their second and third trimesters completed the survey, which included general information questionnaire, Intolerance of Uncertainty Scale, Childbirth Self-Efficacy Inventory, Perceived Partner Responsiveness Scale, and Childbirth Attitudes Questionnaire. Rank sum test was used to compare the scores for the fear of childbirth among different groups and Spearman's correlation was used to analyze the scores for all the scales. In addition, the data were centrally processed by using PROCESS V3.4.1 Model 4 (a simple mediation model), Model 5 (the direct path of the mediation model was regulated), and non-parametric Bootstrap method to test the mediation effect and moderation effect. The study showed that 54.31% of the participants experienced fear of childbirth. Their scores for intolerance of uncertainty, childbirth self-efficacy, and perceived partner responsiveness were 15.00 (8.00), 240.00 (75.00), and 72.00 (19.00), respectively. There were significant differences in the scores for the fear of childbirth scale among pregnant women of different age groups, gestational weeks, employment statuses, and average per capita monthly income of the family ( P<0.05). According to our findings, intolerance of uncertainty directly and positively impacted on fear of childbirth ( β=0.76, P<0.001), with childbirth self-efficacy playing partial mediation role between them, its indirect effect being 0.05 and the contribution rate being 6.17%. In addition, after the scores of Perceived Partner Responsiveness Scale were added to the model, perceived partner responsiveness had no significant predictive effect for fear of childbirth, but the product term of the scores for Perceived Partner Responsiveness Scale and Intolerability Uncertainty Scale had significant predictive effect for fear of childbirth ( β=0.01, P<0.05), which suggested that perceived partner responsiveness also played a moderating role between intolerance of uncertainty and fear of childbirth. Health care providers can help primiparas reduce fear of childbirth and improve their childbirth experience by reducing perceived intolerance of uncertainty, improving family support, and teaching coping strategies.


Neurofibroma of the ureter.
We report a case of neurofibroma of the ureter without other clinical signs of von Recklinghausen's neurofibromatosis. The patient presented with flank pain, and excretory urography, retrograde urography and computerized abdominal tomography demonstrated a ureteral mass. The light and electron microscopic characteristics, as well as the histogenesis of ureteral neurofibroma, are discussed.


Dopamine modulates voltage-activated potassium currents in zebrafish retinal on bipolar cells.
We report a study of the characterization of voltage-activated potassium (K+) currents in retinal ON bipolar cells in zebrafish. At single-channels levels, the open probability of the K+ channels increased when the membrane potential was increased. The maximal open proportion was 0.76+/-0.05 under our testing conditions. In whole-cell recordings, the K+ current displayed two exponential components with the activation time constants of 11-22 msec (tau1) and 0.8-4 msec (tau2). Dopamine modulated the K+ current. Dopamine reduced the time constant tau2 when the membrane potential was depolarized to high voltages. A decrease in K+ current was seen when dopamine D1 receptors were selectively activated by SKF38393 or when the D1 receptor-coupled G-proteins were activated by GTP-gamma-S. The activation of adenylate cyclase by forskolin or the increase of intracellular cAMP concentrations by 8-Br-cAMP or Sp-cAMPS also resulted in a decrease in K+ current. Together, the data suggest that dopamine modulates the K+ current via D1 receptor-coupled G-protein pathways.


Desmoplastic infantile ganglioglioma with associated giant aneurysm—case report.
Desmoplastic infantile ganglioglioma (DIG) and supratentorial giant cerebral aneurysm are each extremely rare entities in infants. Here, we present the case of an 8-day old boy who had both of these conditions concurrently. To our knowledge, there is no previous case reported of a patient with coexisting DIG and giant aneurysm.


[The second step in the construction of a stigma scale of epilepsy].
The issue of stigmatization is one of the most common psychosocial problems faced by people with epilepsy. A second step towards the development of a scale to measure epilepsy stigma. We applied a closed questionnaire to 12 patients and 32 relatives from the Epilepsy Outpatient Clinic at the University Hospital of Campinas. The results are grouped in three main domains: medical, social and personal areas. Medical: the subjects did not know exactly what epilepsy is or how it is caused; nonetheless they know how to treat it. Social: the most important areas that people with epilepsy are discriminated are at work and social relationships. Patients also complained about their lack of freedom and limits on recreation activities. Personal Area: subjects apparently have the same feelings and thoughts about epilepsy and seizures. This study analyzed the most common aspects presented in the questionnaire to assess epilepsy stigma for the Brazilian culture which are the base to the elaboration of a stigma scale of epilepsy.


An open-label pilot study of quetiapine plus mirtazapine for heavy drinkers with alcohol use disorder.
Animal research suggests that medications that produce a weak dopamine D2 receptor blockade and potentiate noradrenergic activity may decrease alcohol drinking. In an open-label pilot study of subjects with alcohol dependence, we tested whether the combination of quetiapine, a weak dopamine D2 receptor antagonist, whose primary metabolite, desalkylquetiapine, is a norepinephrine reuptake inhibitor, and mirtazapine, a potent α2 norepinephrine receptor antagonist, would decrease alcohol drinking and craving. Twenty very heavy drinkers with alcohol dependence entered a trial of 8 weeks of treatment with quetiapine followed by 8 weeks of treatment with a combination of quetiapine plus mirtazapine. Alcohol use was assessed weekly with a Timeline Follow-Back interview and craving with the Penn Alcohol Craving Scale. Among the 11 completers, subjects reported improved outcomes in the quetiapine plus mirtazapine period compared to the quetiapine alone period: fewer very heavy drinking days per week (1.3 [SD = 2.4] vs. 2.1 [SD = 2.8]; t = 2.3, df = 10, p = 0.04); fewer total number of drinks per week (39.7 [SD = 61.6] vs. 53.4 [SD = 65.0]; t = 2.8, df = 10, p = 0.02); and lower craving scores (2.5 [SD = 1.4] vs. 3.2 [SD = 1.2]; t = 2.4, df = 10, p = 0.04). All subjects reported at least one adverse event; 72.7% reported somnolence. In this open-label pilot study, treatment with quetiapine plus mirtazapine was associated with a decrease in alcohol drinking and craving. These findings are consistent with our previous work in animal models of alcohol use disorders and suggest that further study of medications or combinations of medications with this pharmacologic profile is warranted.


Enzymes involved in branched-chain amino acid metabolism in humans.
Branched-chain amino acids (leucine, isoleucine and valine) are structurally related to branched-chain fatty acids. Leucine is 2-amino-4-methyl-pentanoic acid, isoleucine is 2-amino-3-methyl-pentanoic acid, and valine is 2-amino-3-methyl-butanoic acid. Similar to fatty acid oxidation, leucine and isoleucine produce acetyl-coA. Additionally, leucine generates acetoacetate and isoleucine yields propionyl-coA. Valine oxidation produces propionyl-coA, which is converted into methylmalonyl-coA and succinyl-coA. Branched-chain aminotransferase catalyzes the first reaction in the catabolic pathway of branched-chain amino acids, a reversible transamination that converts branched-chain amino acids into branched-chain ketoacids. Simultaneously, glutamate is converted in 2-ketoglutarate. The branched-chain ketoacid dehydrogenase complex catalyzes the irreversible oxidative decarboxylation of branched-chain ketoacids to produce branched-chain acyl-coA intermediates, which then follow separate catabolic pathways. Human tissue distribution and function of most of the enzymes involved in branched-chain amino acid catabolism is unknown. Congenital deficiencies of the enzymes involved in branched-chain amino acid metabolism are generally rare disorders. Some of them are associated with reduced pyruvate dehydrogenase complex activity and respiratory chain dysfunction that may contribute to their clinical phenotype. The biochemical phenotype is characterized by accumulation of the substrate to the deficient enzyme and its carnitine and/or glycine derivatives. It was established at the beginning of the twentieth century that the plasma level of the branched-chain amino acids is increased in conditions associated with insulin resistance such as obesity and diabetes mellitus. However, the potential clinical relevance of this elevation is uncertain.


Extended local access fibers: adjustable treatment of deep sites in the brain.
We describe a minimally invasive method for administering diffusible substances to computer-targeted regions of the primate brain. Treatments enter the brain by diffusion or under pressure from the portion of a curvilinear implant that lies within the region of interest. During the implantation surgery, a guide-tube cannula is passed through a cranial burr-hole and concentric, telescoping needles are extended from the cannula in sequence to trace a pre-planned course through brain tissue. After the leading end of the longest needle emerges through another burr-hole, the surgeon fastens a hollow dialysis fiber to its tip and draws the fiber into the brain by retracting the telescoping device in an orderly sequence. The surgery affects brain tissue only along the course of the fiber, causing about the same acute damage as the stereotactic introduction of an ordinary straight needle. The 'extended local access fiber' is relatively soft, flexible, and biocompatible. It remains permanently in the brain, with its semipermeable portion lodged in the target region. Leading and trailing portions are accessible from outside the brain. Experiments indicate a broad range of possible trajectories and confirm that substances delivered by access fiber can have physiological effects even 10 weeks after implantation.


Primary health care in northwestern Somalia: a case study.
This paper examines the problem of initiating health care programmes in areas where there is no effective infrastructure. The problem is examined using Northwestern Somalia as a case study. The project focussed on the establishment of well-trained and well-supported CHWs at the community level. Many of these communities are (semi-)nomadic. The roles of middle-level management staff, community leaders and committees, CHW remuneration and health effects of the project are discussed.


Stability-indicating capillary zone electrophoresis method for the assessment of recombinant human interleukin-11 and its correlation with reversed-phase liquid chromatography and biossay.
A stability-indicating capillary zone electrophoresis (CZE) method was validated for the analysis of recombinant human interleukin-11(rhIL-11) using rupatadine fumarate, as internal standard (IS). A fused-silica capillary, (50 µm i.d.; effective length, 40 cm) was used at 25°C; the applied voltage was 20 kV. The background electrolyte solution consisted of 50 mmol L(-1) sodium dihydrogen phosphate solution at pH 3.0. Injections were performed using a pressure mode at 50 mbar for 45 s, with detection by photodiode array detector set at 196 nm. Specificity and stability-indicating capability were established in degradation studies, which also showed that there was no interference of the excipients. The method was linear over the concentration range of 1.0-300 µg mL(-1) (r(2)=0.9992) and the limit of detection (LOD) and limit of quantitation (LOQ) were 0.2 µg mL(-1) and 1.0 µg mL(-1), respectively. The accuracy was 100.4% with bias lower than 1.1%. Moreover, the in vitro cytotoxicity test of the degraded products showed significant differences (p<0.05). The method was applied for the content/potency assessment of rhIL-11 in biopharmaceutical formulations, and the results were correlated to those of a validated reversed-phase LC method (RP-LC) and an TF-1 cell culture assay, showing non-significant differences (p>0.05). In addition the CZE and RP-LC methods were applied for the analysis of rhIL-11 in human plasma. Therefore, the proposed alternative method can be applied to monitor stability, to assure the batch-to-batch consistency and quality of the bulk and finished biotechnology-derived medicine.


Metallic nickel nanoparticles supported polyaniline nanotubes as heterogeneous Fenton-like catalyst for the degradation of brilliant green dye in aqueous solution.
Metallic nanoparticles supported on porous matrices are promising heterogeneous catalysts for Fenton-like reaction towards the degradation of organic contaminants in water. Herein, novel magnetic nanocomposites (NCs) of metallic nickel (Ni0) nanoparticles and nanotubular polyaniline matrix (PANI/Ni0 NCs) were fabricated by simple reductive formation of Ni0 nanoparticles upon the pre-synthesized PANI nanotubes (NTs) surface and applied as heterogeneous Fenton-like catalyst in degrading cationic brilliant green dye (BG) in aqueous solution. Various physico-chemical characterization techniques revealed effective supporting of soft ferromagnetic well dispersed nano-dimensional Ni0 particles onto the PANI NTs matrix. Heterogeneous Fenton-like catalytic performance of PANI/Ni0 NCs for BG degradation in the presence of hydrogen peroxide (H2O2) oxidant demonstrated their superiority when compared with unsupported Ni0 nanoparticles counterpart. Experiments with a minimum 0.1 g/L of NCs and 10 mM of H2O2 displayed complete degradation of 100 mg/L BG within 120 min reaction time. Improved BG degradation was observed with increase in the dose of PANI/Ni0, H2O2 concentration and temperature, whereas it reduced with rise in initial concentration of BG. The rate of degradation was well described by the pseudo-first- order kinetic model. Six consecutive BG degradation experiments confirmed NCs reusability without loss of original (∼100%) degradation efficiency up to the fifth cycle. Finally, liquid chromatography-mass spectrometric (LC-MS) analyses of the BG samples after 120 min degradation time exposed the formation of N,N-diethylaniline as degradation product along with partial mineralization of the other end products via the attack of reactive hydroxyl radicals (HO•) produced in the catalytic system.


Taurine concentration in human blood peripheral lymphocytes: major depression and treatment with the antidepressant mirtazapine.
Major depression is a serious disease with various systemic effects, including dysfunction of the immune response. Taurine has been known to be related to certain modifications of the immune system. The aim of this study was to determine the taurine concentration in lymphocytes of patients with major depression and to evaluate the influence of the antidepressant treatment with mirtazapine for six weeks on the levels of taurine. Gamma-aminobutyric acid, aspartate, glutamate and glutamine were also determined. Taurine, aspartate and glutamine levels were increased in the lymphocytes of depressed patients before mirtazapine treatment compared to the control group, and were normalized after treatment. Gamma-aminobutyric acid and glutamate did not differ between patients and controls. There was a significant and positive correlation between the severity of the disorder, measured by the Hamilton Rating Scale, and the concentration of taurine in the lymphocytes of depressed patients before treatment. This correlation was not observed after treatment and neither was there a correlation observed for the other amino acids. The present observations could be an indication of the relevance of taurine as a protective agent in the lymphocytes of patients with severe depression, and could be the result of modifications of taurine transport or efflux processes.


Brainstem auditory evoked responses alteration in twin neonates.
The authors obtained BAER recordings for 20 premature twins and 20 premature non-twins. The two groups were comparable as to conceptional age (36-37 weeks), gestational age, chronological age, birthweight, sex ratio and head size. The results showed a prolongation of the central conduction time (I-V interval) in the premature twins. This may be due to the intra-uterine growth retardation of twins.


Betel nut indulgence as a cause of epilepsy.
We report a 29-year-old man with secondarily generalised seizure and cardiac impairment. He was an indulger in betel nuts without other aetiological or precipitating factors, and no abnormality on neuroradiologic investigation. The occurrence of his seizures related to an overdose of betel nuts. It is clinically important to know that epilepsy may be induced by betel nut chewing.


RSV P-protein impairs extrinsic apoptosis pathway in a macrophage-like cell line persistently infected with respiratory syncytial virus.
Disabling apoptosis is practically a mandatory step for establishing and maintaining viral persistence in host cells. Thus, persisting viruses have evolved strategies to impair apoptosis mechanisms. Apoptosis can be induced through either the intrinsic or the extrinsic pathway. Previously, we reported that staurosporine-induced intrinsic apoptotic pathway was down-regulated in a macrophage cell line persistently infected with respiratory syncytial virus (RSV, MΦP). In the present study, our results showed that the extrinsic apoptotic pathway was also impaired in this cell line and that RSV P-protein interfered with the onset of the extrinsic apoptotic process. In this work, we analyzed and compared the expression of several components of the DISC complex (i.e., TNF-α, TNFR1, caspase-8, and cIAP2) in MΦP cells with that in mock-infected macrophages. Additionally, by using DNA sequence analysis in silico, we searched for an RSV protein putatively interfering with the triggering of the extrinsic apoptotic process. The analysis showed that viral P-protein shared a 52% homology with the caspase-8 death domain. Subsequently, the nucleic acid sequence of the viral P-protein was cloned and transfected into the macrophage cell line; the effect of this transfection on staurosporine-induced apoptosis was evaluated by assaying for cell viability and caspases-8 and -9 activity. The results revealed that although caspase-9 was activated, the activity of the caspase-8 was impaired in the RSV P-protein transfected cells; more of these cells survived than did mock-transfected cells. These findings suggest that P-protein impaired the extrinsic pathway of apoptosis. Our findings contribute to the understanding of the mechanism by which viral proteins subvert the extrinsic apoptosis process in cells persistently infected with RSV.


Propagation phase-contrast micro-computed tomography allows laboratory-based three-dimensional imaging of articular cartilage down to the cellular level.
High-resolution non-invasive three-dimensional (3D) imaging of chondrocytes in articular cartilage remains elusive. The aim of this study was to explore whether laboratory micro-computed tomography (micro-CT) permits imaging cells within articular cartilage. Bovine osteochondral plugs were prepared four ways: in phosphate-buffered saline (PBS) or 70% ethanol (EtOH), both with or without phosphotungstic acid (PTA) staining. Specimens were imaged with micro-CT following two protocols: 1) absorption contrast (AC) imaging 2) propagation phase-contrast (PPC) imaging. All samples were scanned in liquid. The contrast to noise ratio (C/N) of cellular features quantified scan quality and were statistically analysed. Cellular features resolved by micro-CT were validated by standard histology. The highest quality images were obtained using propagation phase-contrast imaging and PTA-staining in 70% EtOH. Cellular features were also visualised when stained in PBS and unstained in EtOH. Under all conditions PPC resulted in greater contrast than AC (p < 0.0001 to p = 0.038). Simultaneous imaging of cartilage and subchondral bone did not impede image quality. Corresponding features were located in both histology and micro-CT and followed the same distribution with similar density and roundness values. Three-dimensional visualisation and quantification of the chondrocyte population within articular cartilage can be achieved across a field of view of several millimetres using laboratory-based micro-CT. The ability to map chondrocytes in 3D opens possibilities for research in fields from skeletal development through to medical device design and treatment of cartilage degeneration.


Study of correlation between lead-induced cytotoxicity and nitric oxide production in PC12 cells.
Despite reduction in its exposure, lead remains a major health problem. The primary target of lead toxicity is the central nervous system. The cellular, intracellular and molecular mechanisms of lead neurotoxicity are numerous, such as induction of apoptosis and interfering with Ca2+ dependent enzyme like nitric oxide synthase (NOS). To investigate the cytotoxic effect of lead on rat pheochromocytoma (PC12) cells, as a suitable model for neuroscience study, and possible correlation between lead toxicity and nitric oxide (NO) production, this study was performed. The current results showed that lead could induce cytotoxicity as well as NO production in a dose dependent manner in PC12 cells after 24h. The cytotoxicity was positively correlated with increased NOx (nitrite and nitrate) production in these cells. L-NAME, a NOS inhibitor, treatment (2.5 mM) could reverse this cytotoxicity. It can be concluded that lead-induced cytotoxicity in PC12 cells could partly be mediated by higher NO production.


Visual exploration of structure-activity relationship using maximum common framework.
To help tracking all molecules made in a typical medicinal chemistry project, we have developed an algorithm to generate a maximum common framework (MCF) hierarchy and an interactive tool for its visualization and analysis. By identifying all unique frameworks for a set of molecules and all molecules containing each framework, we were able to simplify the MCF hierarchy build up steps and, as a result, speed up the entire process significantly. By allowing compounds to be assigned to multiple MCFs, users can easily remove bad branching nodes and concentrate on interesting ones. MCF hierarchies provide an effective and intuitive visualization for tracking medicinal chemistry lead optimization projects. We will provide examples to illustrate its usefulness.


[Rupture of an infective aneurysm of the sub-renal abdominal aorta into the inferior vena cava. One case (author's transl)].
An aorto-caval fistula developed in a 62-year-old woman secondary to the rupture of an infective aneurysm of the aortic bifurcation. Treatment in relation to local and, above all, general infection is discussed, emphasising the value of epiplooplasty and prolonged appropriate antibiotic therapy. However, adequate follow-up is essential in order to be able to affirm cure, recurrence of the infectious process always being possible, even late.


Role of growth hormone in the amino acid-induced acute rise in renal function in man.
To examine whether plasma growth hormone is necessary for the amino acid-induced rise in effective renal plasma flow (ERPF, PAH clearance) and GFR (inulin clearance), arginine HCl, 500 mg/kg, was infused for 30 minutes into eight normal and six growth hormone-deficient individuals. During infusion, ERPF increased in the normal and growth hormone-deficient subjects by 28.9 +/- 11.4 SD-% (P less than 0.01) and 46.5 +/- 14.4% (P less than 0.001). GFR rose by 23.7 +/- 5.9% (P less than 0.05) and 42.7 +/- 29.1% (P less than 0.001) in the two groups. Plasma growth hormone rose only in the normal subjects, while glucagon increased in both groups. Infusion of arginine HCl, 200 mg/kg, into normals increased ERPF and GFR without increasing plasma osmolality. Lower arginine doses essentially did not affect ERPF, GFR, growth hormone, or glucagon. Infusion of D-glucose into normals raised plasma osmolality as high as with arginine HCl, 500 mg/kg, but increased ERPF only slightly and not GFR; D-glucose infusion caused a delayed rise in growth hormone that was unassociated with an increase in ERPF or GFR. An infusion of ammonium chloride with sodium chloride, which provided an amount of chloride similar to the 500 mg/kg arginine HCl dose, did not change ERPF and GFR; this suggests that the chloride load did not cause the altered renal hemodynamics stimulated by arginine HCl. These findings indicate that neither normal plasma growth hormone levels nor a rise in growth hormone mediates the arginine-induced acute increase in ERPF or GFR. This effect is also not due to the osmolar load but could be caused by the rise in plasma glucagon.


Correlation between anti-malarial and anti-haemozoin activities of anti-malarial compounds.
Despite noticeable improvement in anti-malarial treatment, rapid growth of resistant malaria strains points out the need for continuous development of novel anti-malarials to fight the disastrous infection. Haemozoin is considered as a novel inhibitory pathway for new anti-malarial drugs, therefore, this study aimed to systematically review all articles investigating the correlation between anti-malarial and anti-haemozoin activities of anti-malarial compounds. A literature search was conducted on 22 October 2017 in eight databases for relevant in vitro articles reporting the correlation between anti-malarial and anti-haemozoin of anti-malarial compounds, based on the constructed search terms and inclusion criteria. ToxRtool was used to assess quality of each study. A total of ten articles were included in the review. In vitro anti-malarial and anti-haemozoin activity had a good correlation for quinolines for sensitive strains (R2 ranging from 0.66 to 0.95) and xanthones (Spearman ρ = 0.886). However, these correlations were reached after removing some compounds which had non-detectable anti-malarial or anti-haemozoin effects. Other structures (acridines, pyrolidines) showed negligible correlation with Spearman ρ ranging from 0.095 to 0.381 for acridines, and r varying from 0.54 to 0.62 for pyrolidines. Some good correlations were only shown in a logarithmic manner or when the anti-malarial activity was normalized. The results raised a relative relationship between anti-haemozoin and in vitro anti-malarial activities. Some studies reported compounds that were effective in the inhibition of haemozoin formation, but failed to inhibit the parasite survival and vice versa. The correlation results in these studies were calculated after these compounds were removed from their analysis. The ability of anti-malarial compounds to accumulate inside the reaction site might strengthen their anti-malarial activity.


Different systems in human brain are involved in presemantic discrimination of pictures as revealed by event-related potentials.
It is uncertain if the several brain areas in response to presemantic picture processing are functionally homogeneous. Subjects were asked to discriminate visual stimulus pairs and event-related potentials (ERPs) were recorded from the scalp. A line-drawing picture (S1) was followed by another stimulus (S2) 600 ms later. S2 was the same as S1 in condition 1, a reversed picture of S1 in condition 2, the corresponding Chinese word in condition 3 and the syllabic alphabet of S1 in condition 4. Amplitudes of ERPs over right posterior scalp with time window from 102-180 ms after the onset of S2 in condition 1 and 2 were significantly larger than condition 3 and 4. The N2 component on the right anterolateral scalp with time window from 182-240 ms was significantly larger in condition 1 than other conditions, whereas the N2 on the left anterolateral scalp with time window from 262-350 ms in condition 2, 3 and 4 was significantly larger than condition 1. It is suggested that pictures and words are processed in different systems at the presemantic stage: repetitive and physically deviant stimuli evoke different responses in different brain regions.


Eugenol and geraniol impede Csu-pilus assembly and evades multidrug-resistant Acinetobacter baumannii biofilms: In-vitro and in-silico evidence.
Acinetobacter baumannii forms robust biofilms, which aid protection against antimicrobials and account for adaptation in hospital settings. Biofilm formation by A. baumannii has worsens the scenario of drug resistance. Therefore, new strategies are required to tackle biofilm-forming multidrug-resistant A. baumannii. The present study investigated compounds with antimicrobials and antibiofilm properties against A. baumannii. Different antimicrobials were selected from available reports. Initially, comparative antimicrobial activity against A. baumannii isolates was assessed. Most potent antimicrobial compounds were further analyzed for time-kill kinetics, biofilm inhibition, and exopolysaccharide (EPS) reduction in their presence and absence. The antibiofilm potentials were also confirmed with SEM analysis. The relative gene expression of the csuE gene and molecular docking was carried out to investigate the molecular mechanism of mature biofilm disruption. The results demonstrated eugenol and geraniol as the most potent inhibitors with MICs of 6.08 mM and 3.24 mM, respectively, with the potential to significantly inhibit growth and EPS production. Complete inhibition of A. baumannii mature biofilms was observed with a maximum of 60.89 mM and 129.6 mM concentrations of eugenol and geraniol, respectively. The SEM analysis and lower expression of the csuE gene showed the effectiveness of potent antibiofilm agents. In-silico docking showed efficient binding of eugenol and geraniol with the csuE protein of archaic pilus. The findings of molecular docking concordant the assumption that these molecules may prevent the assembly of mature pilus, which results in abolished biofilms. In conclusion, the antibiofilm virtues of eugenol and geraniol were elucidated to be used in the future to control the persistence of biofilm-forming drug-resistant A. baumannii.


Outcomes of acute myocardial infarction in nonagenarians.
To evaluate survival after acute myocardial infarction (AMI) in nonagenarians, we conducted a retrospective chart review of 177 consecutive patients > or =90 years of age admitted from 2000 to 2006 with a primary diagnosis of AMI confirmed by peak troponin I > or =1.5 microg/L. Mean follow-up was 3.7 years (range 4 months to 6.7 years). Mean age was 93 years, 34% were men, and 60% were Caucasian. Common co-morbidities included hypertension (67%), dyslipidemia (28%), atrial fibrillation (28%), renal insufficiency (27%), dementia (23%), and previous cerebrovascular events (22%). Mean peak troponin was 20 mug/L (range 1.5 to 183 microg/L). Cardiac catheterization was performed within 48 hours in 42 patients (24%) and after 48 hours in 14 patients (8%); 40 patients (23%) received an intervention. Hospital mortality was 15% (n = 27). Survival at 30 days, 90 days, and 1 year were 78%, 69%, and 47%. Independent predictors of shorter survival time by Cox analysis included body mass index <25 kg/m2 (p <0.001), creatinine > or =2.0 mg/dl (p = 0.001), hemoglobin <11.0 g/dl (p = 0.016), and dementia (p = 0.027). Patients receiving aspirin, clopidogrel, beta blockers, and renin-angiotensin system inhibitors appeared to have a lower mortality. In conclusion, AMI in nonagenarians is associated with high mortality, with over 50% of patients dying within one year of presentation; elevated creatinine and lower hemoglobin are strong predictors of adverse prognosis, and lower body mass index and the presence of dementia add independent prognostic significance.


Cross-cultural adaptation and psychometric evaluation of the Thai version of Self-Care of Chronic Illness Inventory Version 4.c.
To translate and validate the Thai Self-Care of Chronic Illness Inventory version 4.c (Thai SC-CII v4.c) in individuals with chronic illnesses. A scale translation and cross-sectional validation study was conducted. The English version was translated for Thai involved nine steps: preparation, forward translation, reconciliation, back-translation, back-translation review, harmonization, cognitive debriefing, review of cognitive debriefing and finalization, and proofreading. A cross-sectional study was conducted from July to November 2022 at 16 primary care centers in southern Thailand, involving 410 participants with at least one chronic condition. Validity assessments included structural, convergent, and discriminant validity. Concurrent validity examined correlations between SC-CII v4.c with the Self-Care Self-Efficacy Scale (SCSES) and self-perceived health. Internal coherence reliability was calculated using Cronbach's α coefficient, item-total correlation coefficients, and the composite reliability (CR) index. Thai SC-CII v4.c demonstrated excellent translational validity (κ = 0.99). The specified Self-Care Maintenance model fit well, with minor differences in health promoting behavior and illness-related behavior items compared to the original model. The original Self-Care Monitoring, and Self-Care Management models fit well with Thai data. Simultaneous confirmatory factor analysis confirmed a satisfactory fit of the full SC-CII v4.c. Convergent validity had partial support (average variance extracted = 0.23-0.51), and discriminant validity was established (heterotrait-monotrait ratios = 0.37-0.88). Concurrent validity was supported by positive correlations between each scale and overall SC-CII v.4c with SCSES (r = 0.25-0.65) and self-perceived health (r = 0.09-0.35). The Cronbach's α coefficient were adequate for all scales except the Self-Care Maintenance scale (Cronbach's α = 0.68), but the CR estimate improved the reliability of all three scales (ranging 0.80-0.82). All items had satisfactory item-total correlation coefficients (ranging 0.34-0.71), except the one pertaining to sleep. The Thai SC-CII v4.c is valid and reliable for assessing self-care in various chronic illnesses. Further testing is recommended for patients with specific diseases.


Biochemical propensity mapping for structural and functional anatomy of importin α IBB domain.
Importin α has been described as a nuclear protein transport receptor that enables proteins synthesized in the cytoplasm to translocate into the nucleus. Besides its function in nuclear transport, an increasing number of studies have examined its non-nuclear transport functions. In both nuclear transport and non-nuclear transport, a functional domain called the IBB domain (importin β binding domain) plays a key role in regulating importin α behavior, and is a common interacting domain for multiple binding partners. However, it is not yet fully understood how the IBB domain interacts with multiple binding partners, which leads to the switching of importin α function. In this study, we have distinguished the location and propensities of amino acids important for each function of the importin α IBB domain by mapping the biochemical/physicochemical propensities of evolutionarily conserved amino acids of the IBB domain onto the structure associated with each function. We found important residues that are universally conserved for IBB functions across species and family members, in addition to those previously known, as well as residues that are presumed to be responsible for the differences in complex-forming ability among family members and for functional switching.


Underappreciated roles for Rho GDP dissociation inhibitors (RhoGDIs) in cell function: Lessons learned from the pancreatic islet β-cell.
Rho subfamily of G proteins (e.g., Rac1) have been implicated in glucose-stimulated insulin secretion from the pancreatic β-cell. Interestingly, metabolic stress (e.g., chronic exposure to high glucose) results in sustained activation of Rac1 leading to increased oxidative stress, impaired insulin secretion and β-cell dysfunction. Activation-deactivation of Rho G proteins is mediated by three classes of regulatory proteins, namely the guanine nucleotide exchange factors (GEFs), which facilitate the conversion of inactive G proteins to their active conformations; the GTPase-activating proteins (GAPs), which convert the active G proteins to their inactive forms); and the GDP-dissociation inhibitors (GDIs), which prevent the dissociation of GDP from G proteins. Contrary to a large number of GEFs (82 members) and GAPs (69 members), only three members of RhoGDIs (RhoGDIα, RhoGDIβ and RhoGDIγ) are expressed in mammalian cells.Even though relatively smaller in number, the GDIs appear to play essential roles in G protein function (e.g., subcellular targeting) for effector activation and cell regulation. Emerging evidence also suggests that the GDIs are functionally regulated via post-translational modification (e.g., phosphorylation) and by lipid second messengers, lipid kinases and lipid phosphatases. We highlight the underappreciated regulatory roles of RhoGDI-Rho G protein signalome in islet β-cell function in health and metabolic stress. Potential knowledge gaps in the field, and directions for future research for the identification of novel therapeutic targets to loss of functional β-cell mass under the duress of metabolic stress are highlighted.


Standardized hospital management of pediatric diabetic ketoacidosis reduces frequency of low blood glucose episodes.
In patients treated for DKA, decrease the rate of visits experiencing one or more BG < 80 mg/dl by 10% within 24 months. Plan-do-study-act cycles tested interventions linked to key drivers including: standardized DKA guidelines incorporating a two-bag fluid system, efficient ordering process, and care team education. Inclusion criterion: treatment for DKA with a bicarbonate value (HCO3 ) <15 mEq/L. the percent of patient visits experiencing a BG < 80 mg/dl while undergoing treatment for DKA. Process measures included: order panel and order set utilization rates. Balancing measures included: emergency department and hospital lengths of stay, time to acidosis resolution (time to HCO3 ≥ 17 mEq/L), and admission rates. Outcomes were analyzed using statistical process control charts. From January 2017 through May 2021, our institution treated 288 different patients during 557 visits for suspected DKA. Following our interventions, the overall percent of patient visits for DKA with a BG < 80 mg/dl improved from 32% to 5%. The team did see small improvements in emergency department and hospital lengths of stay; otherwise, there was no significant change in our balancing measures. Use of quality improvement methodology and standardized DKA management resulted in a significant reduction of BG < 80 mg/dl in patients treated for DKA.


MHC class I chain-related gene A-A5.1 allele is associated with ulcerative colitis in Chinese population.
The human MHC class I chain-related gene A (MICA) plays a role in regulating protective responses by intestinal epithelial Vdelta1 gamma delta T cells and the polymorphism of MICA were reported to be related to several autoimmune diseases. The present study aimed to investigate the association of the microsatellite polymorphisms of TM region of MICA gene with the susceptibility to ulcerative colitis (UC) in Chinese population. The microsatellite polymorphisms of the MICA were genotyped in unrelated 86 Chinese patients with UC and 172 ethnically matched healthy controls by a semiautomatic fluorenscently labelled PCR method. All the subjects were the Chinese with Han nationality. The frequency of MICA-A5.1 homozygous genotype and A5.1 allele were significantly increased in UC patients compared with healthy controls (22.1%versus 7%, P = 0.0009, Pc = 0.0126, OR = 3.781, 95%CI: 1.738-8.225 and 30.2%versus 17.4%, P = 0.0014, Pc = 0.007, OR = 2.051, 95%CI: 1.336-3.148, respectively). Adjusted the effects of gender and age at onset, MICA-A5.1 homozygous genotype and A5.1 allele were also increased in the UC patients. Moreover MICA-A5.1 allele was significantly increased in frequency in the female UC patients (38.2%versus 21.0%, P = 0.0095, Pc = 0.0475, OR = 2.326, 95%CI: 1.234-4.382). Logistic regression analysis also revealed that gender was independently associated with UC patients carried MICA-A5.1 allele (P = 0.046, OR (male) = 0.511, 95% CI: 0.264-0.987). Although the UC patients with extensive colitis (32.5%versus 17.4% in the healthy controls, P = 0.005, Pc = 0.025) and the UC patients with extraintestinal manifestations (36%versus 17.4% in the healthy controls, P = 0.0039, Pc = 0.0195) were more likely to carry the MICA-A5.1 allele, EIMs was associated with extent of disease (P < 0.0001, OR (with EIMs) = 3.511, 95% CI 1.747-7.056) and MICA-A5.1 allele was not associated with UC patients with extensive colitis or with EIMs in the logistic regression analysis. Therefore, the MICA-A5.1 homozygous genotype and A5.1 allele were closely associated with UC and the MICA-A5.1 allele was positively associated with the female UC patients in Chinese population.


Neurosyphilis presenting as mania.
General paresis of the insane is a late and severe form of neurosyphilis characterized by nonspecific neuropsychiatric symptoms. There are a limited number of case reports of mood disorders presenting in neurosyphilis, with depressive illness being the most common. We performed a literature review of case reports of secondary bipolar disorder induced by syphilitic infection. Herein reported is a case of a 53-year-old woman who initially presented with symptoms of mania and depression, mimicking bipolar disorder, but was subsequently diagnosed with general paresis of the insane. The present case report emphasizes that if a substantial delay occurs in syphilis diagnosis and management, the patient may have a very poor prognosis.


[Transthoracic approach to the spinal column].
Thoracotomy is used to approach and treat anterior spinal lesions arising from various causes. Between 1990 and 1997, we treated 56 patients (40 men and 16 women) between 14 and 67 years old (mean 38.4). All had spinal lesions that were impossible or difficult to reach by a posterior approach. Thirty-one (55.3%) had suffered spinal damage, 8 (14.3%) had spinal deformities, 7 (12.5%) had metastatic tumors, 5 (8.9%) had herniated discs, 4 (7.1%) had Pott's disease and 1 (1.8%) had osteolysis at D6. Thoracotomy was left-sided in 35 cases (62.5%) and right-sided in 19 (33.9%). Video-assisted thoracoscopy was used twice (3.6%). The level of incision was based on the site of the lesion, and the pleural cavity was opened in all cases except one. The posterolateral pleuro-diaphragmatic fold was dissected and the diaphragm opened for retroperitoneal access in 37 cases (66.1%) of thoracolumbar disease. Orthopedic treatment consisted of autologous bone grafts in all cases and placement of a Kaneda splint in 32 cases (57.1%). One patient had to undergo surgery a second time due to inappropriate placement of the vertebral splint. Pneumothorax occurred in one patient after removal of pleural drains. The incision became infected in one patient, and one case of ileal paralysis was observed. Overall, morbidity was 7.1%. We conclude that thoracotomy offers a good alternative approach to spinal lesions. Results are good and morbidity low.


The FSH beta-subunit promoter directs the expression of Herpes simplex virus type 1 thymidine kinase to the testis of transgenic mice.
The bovine FSH beta-subunit promoter (2.3 kb) was coupled to the coding sequence of the Herpes simplex virus type 1 thymidine kinase (HSV-tk) gene and introduced into mouse embryos. A full-length tk transcript was found in the pituitary and testis. In the testis an additional truncated version of tk mRNA was also expressed. Two sets of primer extension fragments were identified, one corresponding to transcription initiation at or near the cap site of the FSH-beta gene, the other to transcription initiation within the tk gene. Furthermore, the latter, shorter transcript contained a 227 bp deletion. Only the long transcript was translated into immunoreactive tk in the later stages of developing spermatids. The tk protein was also functional in the testes, since spermatogenesis was either arrested or the germinal epithelium almost completely destroyed in transgenic males treated with the antiherpetic agent. If the FSH-beta-HSV-tk transgene also functions correspondingly in the pituitary, these mice will provide a useful model for studies on FSH.


Teeth Damage during General Anesthesia.
Dental injuries during anesthesia, especially when advanced airway management is required, represent a legal problem. Factors such as poor dental condition and excessive pressure during intubation contribute to dental damage. The maxillary central incisors are commonly affected. The objective of this review is to know the incidence of dental injuries in adults undergoing anesthesia that requires airway management. The search was performed in MEDLINE (through Pubmed), ClinicalTrials.gov, Scopus, LILACS (through the Virtual Health Library Regional Portal), and SciELO for all available literature on the subject up to December 2022. Inclusion criteria involved articles that studied patients aged 18 years or older who underwent general anesthesia requiring airway management with tracheal intubation or insertion of a laryngeal mask airway. Of all the articles, nine report dental injury associated with the type of airway management. Only one article does not have dental injury. This study addresses dental injuries related to tracheal intubation during general anesthesia. Although techniques are used to prevent them, these injuries still occur. Laryngoscopy, especially with support on the upper central incisors, can cause damage to the teeth. It is important that the anesthesiologist is aware of dental trauma and that orotracheal intubation or the placement of the laryngeal mask airway is performed systematically and rigorously, always considering the patient's dentition to choose the best approach in each specific situation.


Anorexia in cancer patients: prevalence and impact on the nutritional status.
One hundred and eightysix cancer patients with different types, site and stage of disease, consecutively admitted to the Istituto Nazionale Tumori, Milan, were examined. The purpose of the study was to assess the prevalence of subjective anorexia and to determine whether some nutrition-related indices are different within homogeneous categories of cancer patients, anorectic and non-anorectic. Anorexia was measured on the basis of an appetite score, evaluated with a visual analogue rating scale. Nutritional intake was evaluated by a computerised programme of the habitual food consumption. Nutritional assessment included anthropometric evaluations (triceps skinfold, arm circumference, arm muscle circumference) and biochemical indices (serum albumin, and total iron binding capacity). A nutritional index was then calculated: GNS = P + I + M x 100, where P: actual weight/premorbid weight; I: actual weight/ideal weight; M: actual arm muscle mass circumference/ideal arm muscle mass circumference. The evaluation of the data showed that: (1) The prevalence of subjective anorexia ranged from 1 3 to 2 5 of the patients depending on the type and site of tumour, and stage of disease. (2) Most of the nutritional-related variables were significantly worse in anorectic compared with non-anorectic patients. (3) Within groups of patients with different tumour location, but homogeneous for the presence or absence of subjective anorexia, there is no difference with respect to nutritional indices; except for patients with cancer of the oesophagus and stomach who were always more depleted. (4) Anorexia did not seem to influence the nutritional status in patients with cancer at an early stage (except in cancer of oesophagus and stomach) but it was associated to malnutrition as the disease progressed to more advanced stages.


Arthrokinetic nystagmus and ego-motion sensation.
A compelling illusion of body rotation and nystagmus can be induced when the horizontally extended arm of a stationary subject is passively rotated about a vertical axis in the shoulder joint. Lateral nystagmus with the fast phase beating in the opposite direction to the arm movement was found consistently; the mean slow phase velocity increased with increasing actual arm velocity and reached about 15 degrees/sec; the mean position of the eyes was deviated towards the fast phase as in optokinetic nystagmus, and the nystagmus continued after the cessation of stimulation (arthrokinetic after-nystagmus). The existence of an arthrokinetic circularvection and nystagmus indicates a convergence of vestibular and somatosensory afferents from joint receptors. It is concluded that information about joint movements plays an important role within the multisensory processes of self-motion perception.


Prolongation of porcine islet xenograft survival in mice after therapy with immunosuppressive peptides.
Recently, peptides derived from the heavy chain of HLA-B2702 have been shown to modulate immune responses. In this study, we examined the use of these peptides for immunosuppression in a pig to mouse islet xenograft model. Purified porcine islets were transplanted in autoimmune (non-obese diabetic) and non-autoimmune (streptozotocin-injected CBA or C57/Bl6) diabetic mice. Various dosing regimens of HLA-derived peptides with and without antilymphocyte therapy were administered to recipient mice. Graft rejection was determined by daily serum glucose determinations, and, at selected time points, grafts were removed to demonstrate function and provide immunohistochemical examination. HLA-derived peptides were demonstrated to prolong graft survival in both pretransplant and posttransplant treatment regimens. This effect was increased with concomitant antilymphocyte therapy. Further elucidation of the mechanism of action of these immunomodulatory peptides may help in the development of novel immunosuppressive protocols.


Cooperative development of antimicrobials: looking back to look ahead.
As foundations and governments mobilize to tackle antimicrobial resistance (AMR), several experiments in academic-industrial collaboration have emerged. Here, I examine two historical precedents, the Penicillin Project and the Malaria Project of the Second World War, and two contemporary examples, the Tuberculosis Drug Accelerator programme and the Tres Cantos Open Lab. These and related experiments suggest that different strategies can be effective in managing academic-industrial collaborations, and that such joint projects can prosper in both multisite and single-site forms, depending on the specific challenges and goals of each project. The success of these strategies and the crisis of AMR warrant additional investment in similar projects.


Inhibition of nitric oxide synthase accentuates endotoxin-induced sickness behavior in mice.
Sickness behavior appears to be the expression of a central motivational state that reorganizes an organism's priorities to cope with infectious pathogens. To evaluate the possible participation of nitric oxide (NO) in lipopolysaccharide-induced sickness behaviors, mice were submitted to the forced swim test (FST), open field test and dark-light box test. Food intake and corticosterone plasma levels were evaluated. Lipopolysaccharide (LPS, 100 μg/kg; i.p.) administration increased the time spent floating in the FST and decreased locomotor activity in the open field. Indeed, treatment with LPS decreased the total number of transitions between the dark and light compartments of the apparatus. In addition, LPS reduced food intake and increased corticosterone levels. Pretreatment with L-NAME (30 mg/kg; i.p.) or aminoguanidine (50mg/kg; i.p.) accentuated the behavioral changes induced by LPS in the FST, open field and light-dark box tests as well as induced an increment in hypophagia and in corticosterone levels. These findings confirm previous observations that have reported LPS-induced sickness behaviors. In addition, they provide evidence that the synthesis of NO modulates changes in depressive-like and exploratory behaviors in mice, which is supported by the fact that NO synthase inhibitors also attenuate LPS-induced behavioral changes. In addition, the present study suggests that NO may have a protective role, acting in an inhibitory feedback manner to limit LPS-induced sickness behavior.


Late toxicity after post-prostatectomy intensity modulated radiation therapy: Evaluating normal-tissue sparing guidelines.
Dose-volume histogram (DVH) toxicity relationships are poorly defined in men who receive radiation after radical prostatectomy (RP). We evaluated Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability to minimize late toxicity. 164 men received intensity modulated radiation therapy (RT) to a median prostate bed dose of 66.6 Gy at a median of 22 months after RP. 46% of men were prescribed androgen deprivation therapy and pelvic lymph node irradiation to a median dose of 50.4 Gy. DVH relationships for the rectum, bladder, trigone, and bladder excluding the clinical target volume (bladder-CTV) were analyzed against the Common Terminology Criteria for Adverse Events late grade 2 + (G2+) gastrointestinal (GI) and genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy ≤35, 55%, and bladder-CTV V65, 40 ≤50, 70%) and intact prostate RT institutional guidelines (rectum V70, 65, 40 ≤20, 40, 80% and bladder V70, 65, 40 ≤30, 60, 80%, respectively) guidelines were evaluated. With a median follow-up time of of 33 months, the 4-year freedom from G2 + GI and GU toxicity were both 91%. G2 + GI (n = 12) and GU (n = 15) toxicity included 4% diarrhea (n = 6), 4% hemorrhage (n = 6), 1% proctitis (n = 1), and 4% urinary frequency (n = 7), 1% obstructive (n = 2), 2% cystitis (n = 3), and 3% incontinence (n = 5), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while the institutional intact prostate goals were not achieved in 21% and 25% of cases, respectively. Neither dose to the bladder trigone nor any of the proposed normal tissue goals were associated with late toxicity (P > .1). In the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen deprivation therapy, time from RP to RT, and tobacco history were not associated with toxicity. More than 90% of men were free from late G2 + toxicity 4 years after post-RP intensity modulated RT. No tested parameters were associated with late toxicity. In the absence of established normal-tissue DVH guidelines in the postoperative setting, the use of intact guidelines is reasonable.


Efficient expression of bioactive murine IL12 as a self-processing P2A polypeptide driven by inflammation-regulated promoters in tumor cell lines.
Interleukin 12 (IL12) is a heterodimeric proinflammatory cytokine that has shown promise as an anticancer agent. However, despite encouraging results in animal models, clinical trials involving IL12 have been unsuccessful due to toxic side effects associated with its systemic administration, prompting investigation into new delivery methods to confine IL12 expression to the tumor environment. In this study we used the self-cleaving property of the 2A peptide to express both codon-optimized murine IL12 subunits (muIL12opt) as a self-processing polypeptide (muIL12opt-P2A). We cloned muIL12opt-P2A driven by different inflammation-induced lentiviral expression systems to transduce murine tumor cell lines commonly employed in syngeneic tumor models. We confirmed the inducibility of these systems in vitro and in vivo and demonstrated the successful expression of both IL12 subunits and the release of bioactive IL12 upon proinflammatory stimulation in vitro. Therefore, IL12 release driven by these inflammation-regulated expression systems might be useful not only to address the impact of IL12 expression in the tumor environment but also to achieve a local IL12 release controlled by the inflammation state of the tumor, thus avoiding toxic side effects associated with systemic administration.


Lung Cancer Screening Practices in North Carolina CT Facilities.
The burden of lung cancer in the United States is staggering, with more Americans dying from lung cancer than the next four most common cancers combined. With endorsement of lung cancer screening by the United States Preventive Services Task Force and reimbursement by CMS, the number screened for lung cancer with low-dose CT (LDCT) is anticipated to rise in the near future. In 2015, we conducted a cross-sectional study of mailed surveys to 112 ACR CT facilities across North Carolina to examine recommended guidelines for lung cancer screening, referral patterns, and patient tracking methods. We describe the survey results and compare findings with surveys of academic medical centers. Among 48 respondents (response rate = 42.9%), 54.2% offer lung cancer screening with LDCT (93.1% community and 6.9% academic settings); of these, 70.8% use ACR/CMS guidelines. In lung cancer screening facilities, reported patient volumes are low (average eight patients screened per month, range: 0-30) and patient tracking occurs in 72% of facilities. Among our predominately community-based sample of facilities, we found variation in lung cancer screening guideline usage, number of patients screened, and tracking methods.


Acute hepatocellular drug-induced liver injury probably caused by doxazosin.
Drug-induced liver injury (DILI) is a diagnostic challenge, due to the hepatotoxic potential of drugs, herbs and dietary supplements, the variety of pathological phenotypes and the absence of specific biomarkers.


Identification and characterization of two novel antimicrobial peptides from Japanese sea bass (Lateolabrax japonicus) with antimicrobial activity and MO/MФ activation capability.
Piscidins participate in the innate immune response of fish, which aims to eliminate recognized foreign microbes and restore the homeostasis of immune system. We characterized two piscidin-like antimicrobial peptides (LjPL-3 and LjPL-2) isolated from Japanese sea bass (Lateolabrax japonicus). LjPL-3 and LjPL-2 showed different expression patterns in tissues. After Vibrio harveyi infection, the mRNA expression of LjPL-3 and LjPL-2 was upregulated in the liver, spleen, head kidney, and trunk kidney. The synthetic mature peptides LjPL-3 and LjPL-2 exhibited different antimicrobial spectra. Furthermore, LjPL-3 and LjPL-2 treatments decreased inflammatory cytokine production while promoting chemotaxis and phagocytosis in monocytes/macrophages (MO/MФ). LjPL-2, but not LjPL-3, displayed bacterial killing capability in MO/MФ. LjPL-3 and LjPL-2 administration increased Japanese sea bass survival after V. harveyi challenge, which was accompanied by a decline in bacterial burden. These data suggested that LjPL-3 and LjPL-2 participate in immune response through direct bacterial killing and MO/MФ activation.


Uptake of the human papillomavirus vaccine: a review of the literature and report of a quality assurance project.
The aims of this study were to review predictors of knowledge about human papillomavirus (HPV), HPV vaccine, and factors related to HPV vaccine uptake and report a quality assurance project that evaluated HPV vaccine uptake and three-dose completion rates. The setting was a small private urban pediatric practice. Chart review was used to describe HPV vaccine uptake and dose completion rates in 2007. The convenience sample included 189 girls aged 12 to 21 years with HPV vaccine uptake. During 2007, 153 girls aged 12 to 17 years and 42 girls aged 18 to 21 years were seen at well-child care visits. HPV vaccine uptake was 72% (n = 110) for the younger group and 79% (n = 33) for the older group. There was no significant difference in HPV vaccine uptake by group. One quarter (24%, n = 46) received the HPV vaccine dose at an episodic visit. The dose completion rate was 64% (n = 120). HPV vaccine uptake and dose completion rates were higher than rates reported by the Centers for Disease Control and Prevention. Effective strategies are needed to promote HPV vaccine uptake and dose completion.


Enhancement of the cytotoxicity of titanocene dichloride by aging in organic co-solvent.
Titanocene dichloride exhibits anti-proliferative activity in a wide spectrum of murine and human tumors. Although it is still unclear as to which species are active in biological media, they all readily deliver Ti(IV) to transferrin, the protein that transports iron in the blood. In this article, we report that aging of the complex in alcohols (namely methanol and ethanol) or dimethyl sulfoxide, the co-solvents used to prepare mother solution of the drug, leads to increased cytotoxic activity (i.e. lower IC(50) values) in HCT116 colon cancer cell lines, to a different extent. The TiCp(2)Cl(2) solvolysis was followed by (1)H NMR, ESI-MS, electrochemical and conductivity measurements, and the intracellular Ti(IV) uptake was evaluated.


Fortification of hamburger with calcium, vitamin A, and ascorbic acid.
Patties were prepared from ground beef--some with and some without calcium, vitamin A, or ascorbic acid, either singly or in various combinations. After cooking, the patties were mixed with buns and mayonnaise, ground, and then fed to weanling rats. No single added nutrient or combination of added nutrients seemed to affect flavor, texture, or cooking losses of fat or water. Fortification with calcium and ascorbic acid increased liver storage of vitamin A and decreased liver:body weight ratios.


Primary meningioma of the paranasal sinus.
We report a 17 year old man with a primary ectopic meningioma in the right ethmoid and maxillary sinus. He underwent endoscopic surgery. After total removal of the tumour his subsequent clinical course was good. The clinical and pathologic features of the 32 previously reported cases in the literature are also reviewed. The pathogenesis and treatment of primary paranasal sinus meningioma is briefly discussed.


Stability-indicating high performance thin layer chromatography determination of Paroxetine hydrochloride in bulk drug and pharmaceutical formulations.
A simple selective precise and stability-indicating high performance thin layer chromatographic method of analysis of Paroxetine hydrochloride both as a bulk drug and in formulations was developed and validated. The method employed TLC (Thin Layer Chromatography) aluminum precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of butanol:acetic acid:water (8:2:0.5, v/v/v). This system was found to give compact spots for Paroxetine HCl (Rf, retardation factor, value-0.48+/-0.02). Paroxteine HCl was subjected to acid and alkali hydrolysis, oxidation and photodegradation, where the degraded product was well separated from the pure drug. Densitometric analysis of Paroxetine hydrochloride was carried out in the absorbance mode at 295 nm. The linear regression analysis data for the calibration spots showed good relationship with (regression) r2 = 0.9903 in the amount range of 300-1500 ng (nanogram) per spot. The mean value of co-relation co-efficient, slope and intercept were 0.9903+/-0.001, 5.38+/-0.058 and 182.5+/-2.16 respectively. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 50 and 150 ng, respectively. The drug does not undergo degradation with oxidation, but gets affected in acidic and alkaline conditions. The acid and alkali degradation showed extra peaks at 0.4 and 0.08 Rf, respectively. This indicates that the drug is susceptible to acidic and alkaline medium. As the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one.


Background staining in immunoblot assays. Reduction of signal caused by cross-reactivity with blocking agents.
Certain serum samples produce high background in Western and direct immunoblot assays that detect human serum IgG against specific antigens. We determined that this was due to a reaction between endogenous IgG and the membrane blocking agent (we refer to this as blocking-specific background). Using milk as blocking agent, we screened 107 sera by Western immunoblot or checkerboard immunoblot assays, and found that 6.5% of sera had background intensities sufficient to interfere with the interpretation of final results. Blocking-specific background was also observed using bovine serum albumin and other animal protein-based blocking agents. As the primary antibody in these immunoblot assays was human IgG, we investigated human serum albumin as a blocking agent; this approach eliminated the problem of blocking-specific background.


Chiral ligand-exchange chromatography for diastereo-enantio separation of exametazime.
The diastereo-enantio separation of isomeric mixtures of exametazime (HM-PAO) by liquid chromatography is described using an achiral sorbent (RP-18). A chiral eluent with the initial complex of Cu(II) and the optically active selector N,N-dimethyl-l-phenylalanine (l-DM-PhA), based on the ligand-exchange principle, has been applied. The separation is based on the presence of the immobilized binary complex Cu(l-DM-PhA)(2) and formation of mixed ternary complex. The optimal mole ratio of Cu(II):l-DM-PhA is 1:4, the pH should be between 4.1 and 4.2 and up to 0.8 mM of triethylamine is added for column presaturation with the initial complex. The elution order has been defined using isolated l-HM-PAO via l-HM-PAO L(+)tartrate and meso-HM-PAO obtained by repeated recrystallization from the isomeric mixture of HM-PAO. Complete resolution between all isomers (R(S) from 2.14 to 3.91) and partial resolution for meso(EE)/l-HM-PAO (R(S)=0.83) has been obtained. This means that the proposed chiral ligand-exchange chromatography (CLEC) can be used for determination of the isomeric purity of HM-PAO. This as an alternative method for resolution measurements with chiral columns.


Deceased vs. living donor kidney transplantation in prediction of acute renal allograft rejection using Tc-99m DTPA renal scan.
No data are available regarding different prognostic values of Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scan in kidney transplantation (KT) recipients according to two distinct donor types: deceased donor KT (DDKT) and living donor KT (LDKT). We evaluated whether the interpretation of Tc-99m DTPA renal scan should be different by the donor type in predicting acute renal allograft rejection (AR). One hundred and seven KT recipients (61 DDKT and 46 LDKT) were included in this study. Tc-99m DTPA renal scan was performed 1 week after KT. AR was defined as pathological evidence of renal allograft rejection during the first 6 months of KT. Clinical factors and Tc-99m DTPA renal scan findings were compared between patients with and without AR. To further analyze the effect of the donor type, they were again compared within DDKT and LDKT recipients, respectively. AR occurred in 15 patients (7 DDKT and 8 LDKT recipients). Among all patients, time to peak uptake (TTP) of the cortex (TTPCX) measured by Tc-99m DTPA renal scan was independently predictive of AR. Moreover, TTPKD (TTP of the whole transplanted kidney) and TTPCX were the only predictors of AR among DDKT recipients. The most accurate predictors were TTPCX and kidney area on renal scan for DDKT and LDKT, respectively. However, these parameters could not predict AR for the opposite donor type. AR could be effectively predicted by Tc-99m DTPA renal scan obtained at 1 week post-KT. Different parameters should be applied according to the donor type in the prediction of AR.


Spatial frequency domain imaging for monitoring immune-mediated chemotherapy treatment response and resistance in a murine breast cancer model.
Spatial Frequency Domain Imaging (SFDI) can provide longitudinal, label-free, and widefield hemodynamic and scattering measurements of murine tumors in vivo. Our previous work has shown that the reduced scattering coefficient (μ's) at 800 nm, as well as the wavelength dependence of scattering, both have prognostic value in tracking apoptosis and proliferation during treatment with anti-cancer therapies. However, there is limited work in validating these optical biomarkers in clinically relevant tumor models that manifest specific treatment resistance mechanisms that mimic the clinical setting. It was recently demonstrated that metronomic dosing of cyclophosphamide induces a strong anti-tumor immune response and tumor volume reduction in the E0771 murine breast cancer model. This immune activation mechanism can be blocked with an IFNAR-1 antibody, leading to treatment resistance. Here we present a longitudinal study utilizing SFDI to monitor this paired responsive-resistant model for up to 30 days of drug treatment. Mice receiving the immune modulatory metronomic cyclophosphamide schedule had a significant increase in tumor optical scattering compared to mice receiving cyclophosphamide in combination with the IFNAR-1 antibody (9% increase vs 10% decrease on day 5 of treatment, p < 0.001). The magnitude of these differences increased throughout the duration of treatment. Additionally, scattering changes on day 4 of treatment could discriminate responsive versus resistant tumors with an accuracy of 78%, while tumor volume had an accuracy of only 52%. These results validate optical scattering as a promising prognostic biomarker that can discriminate between treatment responsive and resistant tumor models.


The economic cost of failure in clinical education: a multi-perspective analysis.
Failure by students in health professional clinical education intertwines the health and education sectors, with actions in one having potential downstream effects on the other. It is unknown what economic costs are associated with failure, how these costs are distributed, and the impacts these have on students, clinicians and workplace productivity. An understanding of cost drivers and cost boundaries will enable evidence-based targeting of strategic investments into clinical education, including where they should be made and by whom. This study was designed to determine the additional economic costs associated with failure by students in health professional clinical education. A cost analysis study involving cost identification, measurement, valuation and the calculation of total cost was conducted. Costs were considered from the perspective of the student, the education institution, the clinical educator, the health service placement provider organisation and the government. Data were based on a 5-week clinical education programme at Monash University, Australia. Data were collected using quantitative surveys and interviews conducted with health professional students, clinical educators and education institute staff. Reference group representation was also sought at various education institution and health service organisation levels. A transferable model with sensitivity analysis was developed. There is a total additional cost of US$9371 per student failing in clinical education from the perspective of all stakeholders considered. Students bear the majority of this burden, incurring 49% of costs, followed by the government (22%), the education institution (18%), the health service organisation (10%) and the clinical educator (1%). Strong economic links for multiple stakeholders as a result of failure by students in clinical education have been identified. The cost burden is skewed in the direction of students. Any generalisation of these results should be made with consideration for the unique clinical education context in which each health professional education programme operates.


[Complications of operative treatment of acetabular fractures].
To improve the effect of operative management of acetabular fractures. One hundred and seventy eight acetabular fractures were treated operatively from August 1993 to December 2000. Their functional results and complications were analyzed. One hundred and twelve hips were followed up for an average of 45.7 months. Heterotopic ossification was noted in 26 hips, post-operative osteoarthritis in 22 hips, avascular necrosis of the femoral head in 8 hips, and sciatic nerve injury in 7 hips after operations. No death and infection were found in this series. Ectopic bone formation develops at extended ilio-femoral and Kocher-Langeneck approaches. Cartilaginous injury of the femoral head is contributable to post-operative osteoarthritis, and imperfect reduction is an important factor in the genesis of osteoarthritis.


Post-stroke and vascular depression: a critical review.
Increasing interest in depression within acute and chronic cerebrovascular pathology is justified for its clinical relevance. The scientific community strongly recommends taking into account its identification and management in efforts to reduce disability, the caregiver's burden and the social-economic impact of cerebrovascular disease. Different approaches observed in the literature review make it difficult to generalize about the evidence concerning crucial clinical issues such as diagnostic criteria, impact on functional improvement, selection or timing of depression treatment. Furthermore, the relationship between cerebral lesion location and depression is not agreed, because both hemispheres are reported as prevailing in published case series. On the other hand, vascular depression is commonly related to diffuse subcortical involvement. Because of its clinical and social impact, a definition of the unclear features of depression within acute and chronic cerebrovascular disease is urgently needed.


Summer 2023 ACIP Update: RSV Prevention and Updated Recommendations on Other Vaccines.
The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The ACIP met June 21-23, 2023, to discuss respiratory syncytial virus (RSV) vaccines, influenza vaccines, pneumococcal vaccines, meningococcal vaccines, and COVID-19 vaccines. The ACIP also held a special meeting on August 3, 2023, to discuss RSV prophylaxis in infants. This update summarizes the proceedings of these meetings that are most relevant to the pediatric population. Major updates for pediatric clinicians include a new recommendation for the monoclonal antibody nirsevimab for prevention of RSV disease in all infants, recommendations regarding use of 20-valent pneumococcal conjugate vaccine, and discussion of potential forthcoming changes to meningococcal and COVID-19 vaccination recommendations.


Calcific pancreatitis in a patient with type 5 hyperlipoproteinemia.
The history of a 27-year-old woman with 10 years of episodic abdominal pain and the development of calcific pancreatitis secondary to hyperlipoproteinemia is presented. The relationship between familial and alcoholic hyperlipidemia and pancreatitis is discussed as well as the mechanism of injury to the pancreas.


Ultrasound-guided percutaneous galactography.
We present a new percutaneous ultrasound-guided galactography technique that may be used in patients in whom the conventional technique fails and breast ultrasonography show dilated ducts.


Lexical richness in maternal input and vocabulary development of Turkish preschoolers in the Netherlands.
The present study examined lexical richness in maternal input to Turkish preschool children in the Netherlands and the relationship with their vocabulary. Fifteen Turkish mother-child dyads were videotaped at the age of 3 and 4 in three settings: book reading, picture description and block building. Children's vocabulary in Turkish was measured at the age of 3 and 4 and in Dutch at the age of 5;10. The lexical richness of the input was analysed both quantitatively (tokens) and qualitatively on diversity, density, and sophistication. The results indicate that lexical richness varied largely among mothers, which could partially be attributed to their SES levels and literacy practices. Furthermore, lexical richness differed between the settings, with the highest richness in the book setting. More importantly, lexical richness in maternal input related to the vocabulary of children in L1 (Turkish) and in the longer run also to L2 (Dutch). Quality of the input (diversity, density and sophistication) turned out to be more influential than quantity.


Failure of conventional strategies to improve nutritional status in malnourished adolescents and adults with cystic fibrosis.
The use of oral dietary supplements was compared with dietary counseling in 13 malnourished patients (3 males, mean age 18.1 years) with cystic fibrosis. Energy intake and nutritional status were evaluated over 3 months. There was no significant change in energy intake or percent ideal body weight in either group.


Adherent Ia+ murine cell lines with characteristics of dendritic cells. II. Characteristics of I region-restricted antigen presentation.
The ability of an adherent Ia+, interleukin 1+ (IL-1) tumor cell line (P388AD) to present turkey gamma-globulin (TGG) to primed T lymphocytes was demonstrated and compared with normal antigen-presenting cells (APC) found in mouse spleen. P388AD tumor cells presented TGG to long-term cultures of TGG-reactive T cells (LTTC) and to lymph node-derived T cells which were enriched on nylon wool columns and subsequently depleted of endogenous antigen-presenting cells with anti-Ia antisera and complement. MHC-restricted antigen presentation by P388AD was observed when long-term cultures of TGG-reactive T cells were used as the responding T-cell population. Furthermore, antisera directed against I-region determinants expressed on the P388AD tumor cells inhibited TGG-specific T-cell proliferation in a dose-related fashion, suggesting a functional role for the tumor cell-associated Ia molecules. The kinetics of antigen presentation to LTTC by P388AD were similar to the kinetics observed for splenic APC, although the magnitude of the proliferative response to LTTC to TGG was generally lower when antigen (Ag) was presented by the tumor cells compared to splenic antigen-presenting cells (APC). However, the magnitude of T-cell proliferation of immune lymph node (LN) T cells was comparable when Ag was presented on tumor cells or splenic APC. Several experiments suggested that Ag uptake and/or processing may be less effective in P388AD tumor cells as compared to normal splenic APC. A nonadherent Ia+, IL-1- tumor cell line (P388NA), which was isolated from the same parental tumor as P388AD, was also tested for the ability to present Ag to primed T lymphocytes and Ag-reactive LTTC. In contrast, to P388AD, the nonadherent tumor cell failed to present TGG under identical culture conditions even though Ia molecules were expressed on the tumor cells and Ag uptake had occurred. However, the defect in Ag presentation by P388NA could be corrected if an exogenous source of purified interleukin 1 was supplied to the cultures. A unique opportunity thus exists with both the P388AD and P388NA tumor cell lines to decipher some of the molecular interactions leading to T-cell proliferation during antigen presentation.


PDGFs and their receptors in vascular stem/progenitor cells: Functions and therapeutic potential in retinal vasculopathy.
Vascular stem/progenitor cells (VSCs) include endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and mesenchymal stem cells. VSCs can produce functional and mature vascular cells required to build blood vessels. VSCs therefore play critical roles in vascular repair and regeneration, particularly, in various retinal vasculopathies, in which vascular defects are a devastating pathology. The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are important regulators of numerous physiological events and diseases, and they play key roles in regulating the formation and function of blood vessels. A better understanding of the effects of PDGFs/PDGFRs on VSCs and a thorough elucidation of their therapeutic potential in the treatment of retinal vasculopathies are critical for both basic and translational research and may lead to better therapies for human vascular diseases.


NEDD8 acts as a 'molecular switch' defining the functional selectivity of VHL.
The von Hippel-Lindau (VHL) tumour suppressor protein is important in the E3 ubiquitin ligase ECV (Elongin B/C-CUL2-VHL)-mediated destruction of hypoxia-inducible factor and the promotion of fibronectin (FN) extracellular matrix assembly. Although the precise molecular mechanism controlling the selectivity of VHL function remains unknown, a failure in either process is associated with oncogenic progression. Here, we show that VHL performs its FN-associated function independently of the ECV complex, highlighting the autonomy of these pathways. Furthermore, we show that NEDD8, a ubiquitin-like molecule, acts as a 'molecular switch' in which its covalent conjugation to VHL prohibits the engagement of the scaffold component CUL2 and, concomitantly, activates the association with FN. These findings provide the first mechanistic step in defining the functional selectivity of VHL and explain a previously unrecognized function of NEDD8.


[A specific radioimmunologi determination of plasma estradiol without chromatography during the cycle and in pregnancy and determination of the free non-protein-bound fraction using dialysis].
The plasma concentrations of estradiol were measured by radioimmunoassay without chromatography. The antibody against estradiol was produced in rabbits immunized with 17beta-estra-diol-6-(0-carboxymethyloxime): bovine-serum-albumin. The lower limit of quantitation is 2.6 pg estradiol. A coefficient of variation of 5.9% was ascertained. The recovery of this method is 93% in the range of 89.8 to 95.2%. The concentrations of estradiol during the menstrual cycle are from 30 pg/ml to 300 pg/ml. Estradiol levels during the anovulatory cycle were found below 70 pg/ml. Similar values (2.0 to 2.5%) of percent of unbound estradiol in normal and anovulatory cycle were calculated. The concentrations of estradiol increase in pregnancy on an average of 16 ng/ml. The percentage of free estradiol decreases (up to the 24 weeks of pregnancy) from 2.3% to 1.2%.


Human prostasomes an extracellular vesicle - Biomarkers for male infertility and prostrate cancer: The journey from identification to current knowledge.
Extracellular vesicles (EVs) are gaining attention among the cell biologists and researchers over the last two decades. Prostasomes are considered to be (Evs) secreted by prostate epithelial cells into the semen during emission or ejaculation. Prostasomes contain various proteins required for immune regulation namely, amino and dipeptidyl peptidase; endopeptidase (neutral); decay accelerating factor; angiotensin-converting enzyme. Sperm cells need a few prerequisites in order to fertilize the egg. The role of prostasomes in enhancing the male fertility was reviewed extensively throughout the manuscript. Also, prostasomes have an immunosuppressive, immunomodulatory, antibacterial role in the female reproductive tract, and in some cases they can be used as immunocontraceptive agent to regulate the fertility status. This review will give insights to many active researchers in the field of prostasomal research and male infertility/fertility research. This review will open many unanswered mechanisms of prostasomes with respect to structure-function analysis, fatty acids patterns in diagnosis as well as prognosis of male infertility/fertility. More scientific reports are in need to support the mechanism of prostasomes and its role in immunomodulation. The development of prostasomes as a biomarker for the prostate cancer is still miserable with a lot of controversial results by various researchers.


Variability in the proliferative responsiveness of cultured human vascular smooth muscle cells to alpha-thrombin.
alpha-Thrombin, a key enzyme of the coagulation cascade, is also a potent mitogen for many cell types. In the present study, the responsiveness to alpha-thrombin of cultured human vascular smooth muscle cells (HVSMC) derived from either vein or normal and atherosclerotic arteries was investigated. All HVSMC populations examined responded mitogenically to alpha-thrombin. However, the extent of this response varied between different cell populations. No significant differences were observed between HVSMC derived from vein versus artery or atherosclerotic versus normal tissues. The responsiveness of a specific HVSMC culture to alpha-thrombin was not affected by cell density and remained constant over several passages. Unlike platelet-derived growth factor BB (PDGF-BB), alpha-thrombin did not exhibit any significant chemotactic effects on HVSMC or induce their anchorage independent growth in semi-solid medium. The hypothesis that the observed variability in HVSMC responsiveness to alpha-thrombin is due to the heterogeneity of cultured HVSMC is raised and discussed.


Ion-selective electrodes to monitor osteoblast-like cellular influence on the extracellular concentration of calcium.
In bone tissue engineering, the composition of the ionic extracellular environment (IEE) can determine both cellular fate and a biomaterial's development and performance. Therefore, precise control of the IEE and a perfect understanding of the dynamic changes that it can be subject to due to cellular activity is highly desired. To achieve this, we initially monitored how two standard osteoblast-like cell models that expressed either high or low alkaline phosphatase activity - SAOS-2 and MG63 cells, respectively - affected the extracellular concentrations of calcium and phosphate during long-term cultures. It was observed that cellular influence on the IEE varied greatly between the two models and could be linked to the capacity of cells to deposit calcium in the extracellular matrix. Miniaturized ion-selective electrodes that could allow for real-time monitoring of calcium in a minimally invasive way were then constructed. The electrodes were characterized in standard in vitro cell culture environments, prior to being successfully applied for periods of 24 h, to record the dynamics of cell-induced deposition of calcium in the extracellular matrix, while using osteogenic media of either high or low concentrations of phosphate. As a result, this study provides the background and technological means for the non-destructive evaluation of the IEE in vitro and allows for the optimization and development of better models of bone tissue construction.


Concentrations of serum cotinine across stages of glomerular function among US adult smokers and nonsmokers.
Data from National Health and Nutrition Examination Survey for 1999-2016 were used to investigate variabilities in serum cotinine levels for US adult smokers (N = 8951) and nonsmokers (N = 28,205) aged ≥ 20 years across the stages of glomerular function (GF). Those with serum cotinine levels < 3.3 ng/mL and did not report using any tobacco products during the last 5 days were classified as nonsmokers. Those with serum cotinine levels ≥ 3.3 ng/mL and reported using cigarettes, cigars, pipes, and/or water pipes with or without using e-cigarettes and/or smokeless tobacco products during the last 5 days were classified as nonsmokers. Those who had eGFR > 90 mL/min/1.73 m2 were classified to be in GF stage 1 or GF-1, those with 60 ≤ eGFR ≤ 90 mL/min/1.73 m2 were classified to be in GF-2, those with 45 ≤ eGFR < 60 mL/min/1.73 m2 were classified to be in GF-3A, and those with 15 ≤ eGFR <45 mL/min/1.73 m2 were classified to be in GF-3B/4. Among nonsmokers, except for females and non-Hispanic blacks, adjusted levels of serum cotinine (AGM) decreased relatively sharply from GF-1 to GF-2, stayed relatively stable at GF-2 and GF-3A, and then rose moderately to GF-3B/4. For example, for non-Hispanic whites, AGMs were 0.042, 0.033, 0.031, and 0.037 ng/mL at GF-1, GF-2, GF-3A, and GF-3B/4 respectively. Among smokers, except for females and non-Hispanic blacks, AGMs increased relatively sharply from GF-1 to GF-2 and then decreased from GF-2 to GF-3/4. For example, for males, AGMs were 151.9, 192.0, and 162.9 ng/mL at GF-1, GF-2, and GF-3/4 respectively. AGMs for male smokers were lower than for female smokers at GF-3/4 (162.9 vs. 197.2 ng/mL, p < 0.01). The order of AGMs by race/ethnicity was non-Hispanic blacks > non-Hispanic whites > Hispanics and others at every GF stage. AGMs at GF-3/4 were higher than AGMs at GF-1 for smokers.


Inflammatory Myofibroblastic Tumor: A Case Study.
Inflammatory myofibroblastic tumor (IMT) is a rare benign lesion found in many locations throughout the body and genitourinary tract. Endoscopically and radiographically, these solid lesions cannot be distinguished from malignant bladder tumors. We present the case of a 21-year-old woman who presented with painful obstructive and irritative voiding symptoms of short duration. After extensive preoperative evaluation failed to reveal a definitive diagnosis, the patient underwent partial cystectomy. Final pathology revealed IMT. A high index of suspicion is required for diagnosis of IMT as it is often difficult to distinguish from its malignant counterparts.