Non-fatal suicidal behavior among South Africans : results from the South Africa Stress and Health Study.
Suicide represents 1.8% of the global burden of disease, yet the prevalence and correlates of suicidal behavior in low income countries are unclear. This study examines the prevalence, age of onset and sociodemographic correlates of suicide ideation, planning, and attempts among South Africans. Nationally representative data are from the South Africa Stress and Health Study (SASH), a national household probability sample of 4,351 South African respondents aged 18 years and older conducted between 2002 and 2003, using the World Health Organization version of the composite international diagnostic interview (CIDI). Bivariate and survival analyses were employed to delineate patterns and correlates of nonfatal suicidal behavior. Transitions are estimated using life table analysis. Risk factors are examined using survival analysis. The risk for attempted suicide is highest in the age group 18-34 and Coloureds had highest lifetime prevalence for attempts. Cumulative probabilities are 43% for the transition from ideation to a plan, 65% from a plan to an attempt, and 12% from ideation to an unplanned attempt. About 7.5% of unplanned and 50% of planned first attempts occur within 1 year of the onset of ideation. South Africans at higher risk for suicide attempts were younger, female, and less educated. The burden of nonfatal suicidality in South Africa underscores the need for suicide prevention to be a national priority. Suicide prevention efforts should focus on planned attempts due to the rapid onset and unpredictability of unplanned attempts.


Improved Fine-Tuning of In-Domain Transformer Model for Inferring COVID-19 Presence in Multi-Institutional Radiology Reports.
Building a document-level classifier for COVID-19 on radiology reports could help assist providers in their daily clinical routine, as well as create large numbers of labels for computer vision models. We have developed such a classifier by fine-tuning a BERT-like model initialized from RadBERT, its continuous pre-training on radiology reports that can be used on all radiology-related tasks. RadBERT outperforms all biomedical pre-trainings on this COVID-19 task (P<0.01) and helps our fine-tuned model achieve an 88.9 macro-averaged F1-score, when evaluated on both X-ray and CT reports. To build this model, we rely on a multi-institutional dataset re-sampled and enriched with concurrent lung diseases, helping the model to resist to distribution shifts. In addition, we explore a variety of fine-tuning and hyperparameter optimization techniques that accelerate fine-tuning convergence, stabilize performance, and improve accuracy, especially when data or computational resources are limited. Finally, we provide a set of visualization tools and explainability methods to better understand the performance of the model, and support its practical use in the clinical setting. Our approach offers a ready-to-use COVID-19 classifier and can be applied similarly to other radiology report classification tasks.


Neuroimmune interactions in atopic and allergic contact dermatitis.
The skin is a barrier organ populated by many types of skin-resident immune cells and sensory neurons. It has become increasingly appreciated that neuroimmune interactions are an important component of inflammatory diseases such as atopic dermatitis and allergic contact dermatitis. Neuropeptides secreted from nerve terminals play an important role in mediating cutaneous immune cell function, and soluble mediators derived from immune cells interact with neurons to induce itch. In this review article, we will explore emerging research describing neuronal effector functions on skin immune cells in mouse models of atopic and contact dermatitis. We will also discuss the contributions of both specific neuronal subsets and secreted immune factors to itch induction and the associated inflammatory processes. Finally, we will explore how treatment strategies have emerged around these findings and discuss the relationship between scratching and dermatitis.


Post-antibiotic and post-beta-lactamase inhibitor effects of ceftazidime plus sulbactam on extended-spectrum beta-lactamase-producing Gram-negative bacteria.
To measure the in vitro post-antibiotic effect (PAE) and post-beta-lactamase inhibitor effect (PLIE) of a ceftazidime-sulbactam combination on bacteria producing extended-spectrum beta-lactamases (ESBLs). PAE and PLIE were studied for ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Two ATCC beta-lactamase-negative strains of E. coli and K. pneumoniae were used as controls. The MICs of a ceftazidime-sulbactam combination were determined with a fixed concentration of sulbactam (8 mg/L). The organisms were exposed to the antibiotics at twice the MIC for 2 h before removal of the antibiotics by filtration of the culture. Bacteria on the filter were resuspended in drug-free medium to determine the PAE and in medium containing ceftazidime, at the same concentration as originally present, to determine the PLIE. The PAE of ceftazidime was similar for bacteria producing the same ESBL except for E. coli producing CTX-M-1. PLIE values varied according to the type of beta-lactamase but similar results were observed for the strains producing the same ESBLs. PLIEs were longer than PAEs and were longer when the MICs of ceftazidime were lower. To the best of our knowledge, we describe here for the first time an in vitro PLIE for a ceftazidime-sulbactam combination on different bacteria producing different ESBLs. These findings indicate that suicide inhibitors may be used in combination with third-generation cephalosporins.


Real-world experience with neuromuscular blockade reversal.
Neuromuscular blocking agents are used in many surgical procedures and have enabled new surgical advances. The expanded landscape of neuromuscular blockade (NMB) reversal drugs allows for fast and complete NMB reversal and the reduction of postoperative complications from residual block. In the United States, neostigmine/glycopyrrolate and sugammadex are the primary agents for pharmacologic antagonism of neuromuscular blocking agents. Whereas neostigmine and an anticholinergic have been available for decades, sugammadex has only recently become available. We present real-world cases in a variety of surgical procedures and clinical settings in which the use of NMB reversal agents played a significant role in the patients' clinical outcome. Online access: http://courses.elseviercme.com/nmb/711.


The effect of telephone triage on symptom management in patients with cancer undergoing systemic chemotherapy: A randomized controlled trial.
Patients with cancer experience chemotherapy-related symptoms in the home after treatment in the hospital. This study was conducted to investigate the effect of the telephone triage on symptom management, quality of life, and self-care management in patients with cancer undergoing treatment of systemic chemotherapy. The study was conducted as a single-blind randomized controlled trial. The sample consisted of 65 patients who were randomly assigned to intervention and control groups. A telephone symptom triage protocol (TeleTRIAGE) was applied to the patients in the intervention group during the 2nd, 3rd, and 4th cycles of chemotherapy treatment. The control group received standard nursing care. Pretest and posttest data were collected using a Personal Information Form, the Chemotherapy Symptom Assessment Scale, the FACT-G Quality of Life Scale and the Self-Care Agency Scale. Compared to the control group, the patients in the intervention group showed a decrease in appetite change, symptom severity, and the degree of discomfort in feeling pessimistic and sad (p < 0.05), and their mean quality of life and self-care management scores increased (p < 0.05). It was found that the TeleTRIAGE protocol applied to patients with cancer undergoing treatment of systemic chemotherapy improved symptom management, quality of life and self-care management. www. gov, NCT04162717.


The location of SV40 specific sequences in the heterogeneous nuclear RNA of transformed mouse cells.
Rapidly labelled nuclear RNA from an SV40 transformed mouse 3T3 line was isolated, and different molecular size classes pooled. The fractions were treated with Ehrlich ascites exonuclease III for various lengths of time, and the digestion of the 3' ends of the RNA measured by the appearance of TCA-soluble material. The resulting partially degraded RNA populations were then hybridised to SV40 DNA. The data suggest that a high proportion of the viral specific sequences are located near the 3' ends of heterogeneous nuclear RNA.


Two cyclopeptides from the seeds of Annona cherimola.
Bioassay-guided fractionation of cytotoxic of methanol extract of the seeds of Annona cherimola provided two novel cyclic peptides, cherimolacyclopeptide E (1) and cherimolacyclopeptide F (2), which exhibited significant cytotoxic activity against the KB (human nasopharyngeal carcinoma) cell culture system. The peptide 1 and 2 were elucidated by MS/MS fragmentation experiments using a Q-TOF mass spectrometer equipped with an ESI source, extensive 2D NMR analyses and chemical degradation.


Posttraumatic stress disorder, depression, and non-fatal intentional self-harm in Massachusetts Veterans.
The literature on the association between Posttraumatic Stress Disorder (PTSD) and fatal and non-fatal intentional self-harm (ISH) among Veterans who receive care within the Veterans Health Administration (VHA) is limited in scope and contradictory. The current study examines the association between PTSD and non-fatal ISH in a gender-stratified sample of patients who received care at a Massachusetts VHA treatment facility between 2000 and 2008. VHA electronic medical record data were obtained for patients who received a PTSD diagnosis at a Massachusetts treatment facility (n = 16,004) and a gender/age matched comparison group (n = 52,502). Rate ratios for the association between PTSD and non-fatal ISH were computed adjusting for marital status, depression, alcohol or drug abuse or dependence, anxiety disorder diagnoses and prior ISH and clustering by hospital using Poisson regression. The interaction between PTSD and depression diagnoses in predicting non-fatal ISH was assessed as the departure from additive effects by calculating the interaction contrast (IC) while adjusting for identified confounders. Over the eight year study period 146 (0.91%) of those with PTSD experienced non-fatal ISH, while 71 (0.14%) of those without PTSD experienced non-fatal ISH. Strong adjusted associations between PTSD and non-fatal ISH were found for both male (RR = 3.3, 95% CI = 2.3, 4.6) and female (RR = 16, 95% CI = 4.7, 55) VHA patients. Evidence of an interaction between PTSD and depression diagnoses in predicting non-fatal ISH was found as a departure from additive effects for both sexes, but this association was more marked among women than among men. Our results indicate that non-fatal ISH among women may be more strongly related to PTSD than prior work focusing on suicide has suggested and highlight the importance of gender-stratified examinations of these associations. Further, our results suggest that suicide prevention approaches in the VHA should integrate treatment for PTSD and depression.


The effect of porphyrin and radiation on ferrochelatase and 5-aminolevulinic acid synthase in epidermal cells.
The effects of ultraviolet A (UVA) and blue light on ferrochelatase protein, and its mRNA level, in 5-aminolevulinic acid (ALA)-loaded A431 cells was evaluated. Western blot analysis of ferrochelatase protein showed a protein band of 43 kDa. There was a decrease in the protein concentration 24 h and 48 h after irradiation of these cells. In contrast, as judged by Northern blot analysis, there was no change in ferrochelatase mRNA level. Measurement of ALA synthase activity showed an ALA dose-dependent but radiation-independent decrease of enzyme activity, suggesting an end-product feedback inhibition. Since reactive oxygen species generated by porphyrin-induced photochemical reaction may be involved in the decrease in ferrochelatase protein, the effect of scavengers of reactive oxygen species was evaluated by measuring porphyrin accumulation in irradiated, ALA-loaded A431 cells. Porphyrin accumulation was significantly decreased in the presence of singlet oxygen scavenger sodium azide (0.05 mM, 40.6% suppression) or hydroxyl radical scavenger mannitol (5.0 mM, 45.0% suppression). These data suggest that the photochemical reaction induced by porphyrin and irradiation resulted in a decrease in ferrochelatase protein content, but had no effect on ferrochelatase mRNA level nor on ALA synthase activity. The decrease in protein was partly mediated by the reactive oxygen species.


Teaching giant african pouched rats to find landmines: operant conditioning with real consequences.
Giant African pouched rats recently have been used as mine-detection animals in Mozambique. To provide an example of the wide range of problems to which operant conditioning procedures can be applied and to illustrate the common challenges often faced in applying those procedures, this manuscript briefly describes how the rats are trained and used operationally. To date, the rats have performed well and it appears they can play a valuable role in humanitarian demining.


The weight-conscious adolescent: body image, food intake, and weight-related behavior.
To explore how adolescents who try to lose weight differ from those who do not in relation to body image, food intake, knowledge about food, and sources of information about food, nutrition, and weight loss. Data were collected from 12-15-year-old school students in North Queensland, Australia by questionnaire. Boys who attempted weight loss reduced sweet foods and snacks, while concurrently increasing healthy foods such as fruit, yogurt, and low-fat milk. Girls who attempted weight loss ate breakfast, lunch, snacks, milk, bread, meat, and many sweet and fatty foods less often than other girls. Some reduction in meals, snacks, core foods, and sweet fatty foods, but not savory fatty foods, remained after the weight loss attempt. Boys attempting weight loss had better knowledge about high-fat and high-sugar foods than other boys, but there was no difference for girls. Girls attempting weight loss were more likely than other girls to think that core foods such as bread, potatoes, and dairy products should be reduced, whereas boys were more likely to think that sweet foods should be reduced. The majority of students who had attempted weight loss during the previous year considered themselves overweight, while few weight-conscious students were satisfied with their bodies. The weight-conscious adolescents in this study, especially the girls, exhibited restrictive eating practices and a preoccupation with a slim image. Adolescents need a food culture based on foods to eat rather than foods to avoid, and an understanding of suitable weight-control measures.


Rapid in vitro modulation of [3H]hemicholinium-3 binding sites in rat striatal slices.
The effects of depolarizing concentrations of potassium chloride on the modulation of [3H]hemicholinium-3 binding sites and high affinity choline uptake were examined in vitro. When rat striatal slices were incubated in Krebs buffer for 20 min, [3H]hemicholinium-3 binding sites diminished to 60% of binding measured in fresh un-incubated tissue, and remained stable for 60 min. Upon addition of Krebs buffer containing 40 mM KCl, the number of binding sites increased during a 20 min period, and remained stable for 40 min. Changes in [3H]hemicholinium-3 binding sites closely paralleled changes in high affinity choline uptake. Scatchard analysis revealed that changes in binding result from alterations in the number of binding sites (Bmax), and not in the affinity (KD). These results suggest that neuronal depolarization rapidly alters the velocity of choline transport into cholinergic neurons by increasing the number of available carriers.


Activation of a dormant replication origin is essential for Haloferax mediterranei lacking the primary origins.
The use of multiple origins for chromosome replication has been demonstrated in archaea. Similar to the dormant origins in eukaryotes, some potential origins in archaea appear to be inactive during genome replication. We have comprehensively explored the origin utilization in Haloferax mediterranei. Here we report three active chromosomal origins by genome-wide replication profiling, and demonstrate that when these three origins are deleted, a dormant origin becomes activated. Notably, this dormant origin cannot be further deleted when the other origins are already absent and vice versa. Interestingly, a potential origin that appears to stay dormant in its native host H. volcanii lacking the main active origins becomes activated and competent for replication of the entire chromosome when integrated into the chromosome of origin-deleted H. mediterranei. These results indicate that origin-dependent replication is strictly required for H. mediterranei and that dormant replication origins in archaea can be activated if needed.


Formation of β-Configured Thioglycosides of d-Glucosamine and d-Galactosamine and Synthesis of Protected Human Milk Oligosaccharides.
We report on the stereoselective multigram scale preparation of cyclohexyl- and phenyl thioglycosides of 2-azido-2-deoxy-β-d-gluco- and galactopyranosides from d-N-acetylglucosamine using a catalytic and solvent-free method. Two of the prepared building blocks were used as key intermediates for the synthesis of human milk oligosaccharides LNT and LNnT in their protected form.


Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability.
The poorly soluble drug buparvaquone is used in experimental clinics against the gastrointestinal persisting parasite Cryptosporidium parvum. It was produced as nanosuspension by high pressure homogenisation. Main advantages of nanosuspensions (amongst others) are their increase of saturation solubility and dissolution velocity, improving the bioavailability of drugs. The buparvaquone nanosuspension had a bulk population of about 600 nm (analysed by photon correlation spectroscopy (PCS)). The additional analysis performed with laser diffraction showed that only a very small content of microparticles occurred, which is, for the special features of nanosuspensions, negligible because they were still below 3 microm. Another feature of nanosuspensions is the adhesion properties to surfaces, e.g. mucosa. To further increase the adhesion time of the buparvaquone nanosuspension to C. parvum, the nanosuspension was formulated with hydrogels made from mucoadhesive polymers, e.g. different types of Carbopol and chitosan. Only a small increase of the particle size of the bulk population occurred directly after the incorporation of buparvaquone nanosuspension into the hydrogels. The nanosuspension/hydrogel systems were physically long-term stable over a period of 6 months as indicated by the unchanged particle sizes.


MECHANISM OF "FLAP CLOSURE" AFTER THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE.
Recent studies described that in approximately 14% to 16% of cases of macular holes treated with the inverted internal limiting membrane flap technique, the hole was closed only by a thin layer of inverted internal limiting membrane-"flap closure." The aim of this article was to describe the functional and anatomical results in flap closure macular holes and also the mechanism of flap closure. A retrospective observational study of 149 eyes of 139 patients treated with vitrectomy using the inverted internal limiting membrane flap technique was reviewed to aggregate eyes with flap closure. Complete ophthalmic examination was performed preoperatively and at 7 days, 1, 3, 6, and 12 months after surgery. Flap closure (Group 1) was noted in 24 eyes and other closure types in 125 eyes (Group 2). The mean minimal and base diameters of the macular holes in the flap closure group were greater than those in Group 2 (P < 0.001). The mean postoperative best-corrected visual acuity in the flap closure group (20/100) was lower than that in Group 2 (20/50) (P < 0.001). Flap closure probably enables closure of large macular holes with a higher probability of remaining open without the use of the inverted internal limiting membrane flap technique. Foveal architecture continuously improved.


Development of a disability scale for myotonic dystrophy type 1.
Myotonic dystrophy type 1 (DM1) is a multisystem disorder. Many tests in the literature have evaluated single aspects of DM1 patients, mainly focusing on muscular impairment, without an overall quantification of the different disease-specific neurological features. We developed and validated a new functional scale for DM1 patients based on neuromuscular impairment (NI) and disability. Thirty-three patients were tested in basal condition, 18 were re-evaluated after therapeutic intervention with mexiletine, and 13 at one year follow-up without treatment. The scale includes 21 ordinal items in four areas: neuropsychology, motricity, myotonia and daily life activities. We evaluated inter- and intra-observer reliability (intraclass correlation coefficient, ICC and Spearman correlations, respectively), internal consistency (Cronbach's alpha), external validity (Spearman correlations between each area and other clinical and objective measurements and scales), and sensitivity to clinical changes after treatment or at follow-up. Our analysis provided good results for inter-observer agreement (ICC = 0.72-0.97), intra-observer reliability, and internal consistency for all areas (Cronbach's α > 0.73). Total score and single area subscores were significantly correlated to objective measurements, disease duration and multisystem involvement. Finally, the scale was sensitive to clinical changes disclosing a significant improvement after treatment in the items assessing myotonia, and also to disease progression showing a significant worsening in all areas but myotonia in untreated patients. Our scale provides a new practical measure to evaluate NI and disability of DM1 patients. Further longitudinal studies are warranted to confirm its reliability in tracking disease progression and severity over a longer period of time.


Expediting the growth of plant-based meat alternatives by microfluidic technology: identification of the opportunities and challenges.
The booming demand for a sustainable future food supply has fueled the development of plant-based meat alternatives (PBMAs) to address the challenges of natural resource depletion, growing populations, and climate change. Innovations and technologies are essential for promoting research and industry growth on PBMAs. In this review, we examine microfluidic technology as a powerful tool that offers solutions for removing manufacturers' hurdles by providing meat replacement products that match customers' expectations and discuss its potential to bring PBMAs to the mainstream through high-throughput screening applications, food structure design, and food safety detection and diagnosis. Finally, prospects and challenges for using microfluidics in the research and industrial production of PBMAs are presented.


Methotrexate as a safe immunosuppressive agent during the COVID-19 pandemic.
During the ongoing COVID-19 pandemic, immunocompromised patients are at a higher risk of severe infection, since the immune system has an important role in defeating this disease. This study compares the severity of COVID-19 in patients taking methotrexate with the severity of their family members' illness as patients with normal immune system function. A total of 35 participants, including 14 patients taking methotrexate and 21 patients with normal immune function, entered this study, and the indicators of COVID-19 severity were compared between these two groups. The case group, who were on methotrexate therapy, had significantly less severe COVID-19 based on their symptoms, including fever (p = 0.000) and cough and dyspnea (p = 0.01) as well as in terms of COVID-19 severity indicators such as pulmonary involvement (p = 0.001), ferritin level (p = 0.001), white blood cell count (p = 0.008) and CRP level (p = 0.006), compared to the control group. There was a significant correlation between taking methotrexate and lower severity in COVID-19 disease. The present findings demonstrated that methotrexate does not predispose patients to severe COVID-19; on the contrary, patients taking methotrexate may experience a milder disease, possibly due to their reduced severe inflammatory reactions as a result of inhibited TNFα, lowered IL6, and increased T regulatory cells. According to these findings, methotrexate appears to be a suitable treatment option for patients who need immunosuppressive medications during the COVID-19 pandemic.


Urodynamic assessment of poor responders after botulinum toxin-A treatment for overactive bladder.
Botulinum toxin-A (BTX-A) is effective in treating overactive bladder (OAB) refractory to anticholinergics. Most patients have improvements in symptoms, urodynamic parameters, and quality of life, and a poor response is uncommon. The aim of this study was to determine whether poor responders could be predicted from preoperative urodynamic parameters. Data were collected prospectively from 33 OAB patients with idiopathic detrusor overactivity. All patients underwent intradetrusor injections of 200 U BTX-A. Response to treatment was assessed by patient perception, OAB symptoms, and quality of life data. Urodynamics were conducted at baseline and 4, 12, and 24 weeks postinjection. We performed statistical analysis using the Wilcoxon matched pairs, Mann-Whitney, two-sample, and paired t-tests. Receiver operator characteristic (ROC) curves were plotted for relevant parameters. Five patients had a poor response to treatment. Significant increases in maximum cystometric capacity (MCC), reflex detrusor volume (RDV), and bladder compliance with decreases in maximum detrusor pressures (MDP) on filling were observed in the responders over 24 weeks. Minimal urodynamic benefit was observed in the poor responders group over the same period. When comparing the two groups, baseline MDP in poor responders was 138.0 +/- 30.7 compared with 74.4 +/- 32.6 in the responders (P = 0.0028). ROC analysis suggested that a pretreatment MDP greater than 110 may have predictive value (AUC, 0.946; sensitivity, 0.86; specificity, 1.0) for a poor response to treatment. Very high MDP greater than 110 may predict a poor response to treatment with 200 U of BTX-A. Higher doses may be necessary in these patients.


Perceptual and motor factors in the imitation of simple temporal patterns.
This study investigated the relative importance of perceptual and motor factors in the imitation of simple temporal patterns. Previous research in which subjects tap out interval sequences using one finger has suggested that perceptual factors play an important role in response timing. Studies of bimanual tapping, in contrast, stress the importance of motor interactions between the two hands. In this experiment we compared the ability of subjects to tap out two-interval sequences using one finger, two fingers on one hand, and two fingers on opposite hands. The results showed almost identical performance under the three response conditions. It is suggested that the perceptual relations between intervals in a pattern were the main determinant of performance in this experiment.


Brief sensory experience differentially affects the volume of olfactory brain centres in a moth.
Experience modifies behaviour in animals so that they adapt to their environment. In male noctuid moths, Spodoptera littoralis, brief pre-exposure to various behaviourally relevant sensory signals modifies subsequent behaviour towards the same or different sensory modalities. Correlated with a behavioural increase in responses of male moths to the female-emitted sex pheromone after pre-exposure to olfactory, acoustic or gustatory stimuli, an increase in sensitivity of olfactory neurons within the primary olfactory centre, the antennal lobe, is found for olfactory and acoustic stimuli, but not for gustatory stimuli. Here, we investigated whether anatomical changes occurring in the antennal lobes and in the mushroom bodies (the secondary olfactory centres) possibly correlated with the changes observed in behaviour and in olfactory neuron physiology. Our results showed that significant volume changes occurred in glomeruli (olfactory units) responsive to sex pheromone following exposure to both pheromone and predator sounds. The volume of the mushroom body input region (calyx) also increased significantly after pheromone and predator sound treatment. However, we found no changes in the volume of antennal lobe glomeruli or of the mushroom body calyx after pre-exposure to sucrose. These findings show a relationship of antennal lobe sensitivity changes to the pheromone with changes in the volume of the related glomeruli and the output area of antennal lobe projection neurons elicited by sensory cues causing a behavioural change. Behavioural changes observed after sucrose pre-exposure must originate from changes in higher integration centres in the brain.


Arcus tendineus fascia pelvis: a further understanding.
The study was undertaken to further define the anatomy of the arcus tendineus fascia pelvis (ATFP). Thirty cadavers were dissected to find the average length, SD, and range of the ATFP. Comparisons were made to height and pelvis type. The average distance between the ischial spine and the attachment of the fascia of the rectovaginal septum (RVF) to the ATFP was measured. The average length, SD, and range in centimeters for the ATFP are 9.0, 0.70, and 7 to 10.5, respectively. The length of the ATFP increased with height. No associations could be made regarding pelvis type. The average distance between the ischial spine and the attachment of the RVF to the ATFP is 2.15 cm with a SD and range of 0.21 and 1.75 to 2.5, respectively. In this study, an average length for the ATFP is established and the distance between the ischial spine and the attachment of the RVF to the ATFP is redefined.


Methods for analyzing and interpreting cooperativity in dose-response curves--I. Antagonist effects on angiotensin receptors in smooth muscle.
1. Dose-response curves for angiotensins II and III in the rat isolated uterus, portal vein and aorta, in the absence and presence of the antagonist [Sar1Ile8]ANG II, have been analyzed by methods which detect cooperativity. 2. Hanes-Woolf transformations of dose-response data were used to define phases of positive homotropic cooperativity, and this information was applied to the interpretation of Hill plots. 3. The level of positive cooperativity was found to be higher for ANG II (nH = 1.35-2.00) than ANG III (nH = 1.02-1.43) in the three tissues studied. 4. In the presence of the antagonist [Sar1Ile8]ANG II a decrease in the level of cooperativity produced by both agonists was observed, and high concentrations of the antagonist could induce negative cooperativity. 5. These findings have been interpreted on the basis of a 2-site agonist binding mechanism involving receptor dimers, in which angiotensin agonists induce an increase in their own receptor binding affinity, whereas the antagonist [Sar1Ile8]ANG II decreases the affinity of angiotensin receptors for ANG II and ANG III.


Schwannoma of the biliary tract resembling cholangiocarcinoma: A case report and review.
Schwannomas are benign tumours derived from Schwann cells and are extremely rare in the biliary tract. We present the case of a 62-year-old patient with a common bile duct schwannoma that resembled a cholangiocarcinoma. We also review all 17 previously published cases of schwannoma of the biliary tract and discuss the challenges of preoperative diagnosis.


Clinical and experimental findings in Acanthamoeba keratitis with Heidelberg Retina Tomograph III-RCM.
To observe Acanthamoeba cysts and trophozoites in the corneal tissue of patients and rabbits with Acanthamoeba keratitis (AK), using the Heidelberg Retina Tomograph III Rostock-cornea-module (HRTIII-RCM). Eight eyes of seven patients with clinical and laboratory diagnosis of AK, presenting to the Beijing Institute of Ophthalmology between July and December 2006, were included in this study. The laboratory diagnosis in all cases was established by a cytological analysis and culture of the corneal scraping. The scanning with HRTIII-RCM was performed on all the patients. Acanthamoeba cysts and trophozoites in the corneas of three rabbits were observed with the HRTIII-RCM after a suspension of trophozoites was injected into the corneal stromal layer of the rabbits. Acanthamoeba cysts or trophozoites were observed with the HRTIII-RCM in the corneas of all the patients. The size and shape of Acanthamoeba in the tissue of the rabbit corneas was consistent with that in the patients' eyes. The Acanthamoeba cyst presented a round high-contrast particle, 15-20 microm in diameter, with a double wall. In contrast, the trophozoite presented an irregular high-contrast particle, without an apparent wall, 25-40 microm in diameter and with a round conspicuous nucleus. HRTIII-RCM is a useful non-invasive clinical technique to help to diagnose and monitor the response of AK to therapy.


Uptake of serotonin by intrinsic neurons of the myenteric plexus grown in organotypic tissue culture.
The myenteric plexus contains axons, not found elsewhere in the peripheral nervous system, which are distinguished by a specific, high affinity transport system for serotinin (5-HT). This study was undertaken to determine the location of the cell bodies of origin of these axons. Vagotomy decreased uptake of [3H]5-HT and tritiated norepinephrine ([3H]NE) by the myenteric plexus. However, while examination by histofluorescence revealed the presence of descending vagal adrenergic fibers, no evidence was found for the presence or accumulation of 5-HT above a vagal ligature. Vagus nerves thus contain adrenergic but not serotonergic axons. The gut was also denervated of all extrinsic axons by growth of intestinal explants in organotypic tissue culture for 3 weeks. Uptake of [3H]5-HT persisted while uptake of [3H]NE was lost. Light and quantitative electron microscopic radioautography revealed that, as in intact gut, the elements of the cultures responsible for uptake of [3H]5-HT were axons distinguished by varicosities containing large dense cored vesicles. In conclusion, these experiments establish that the mammalian gut contains intrinsic neurons which selectively take up 5-HT. The capacity of these neurons for 5-HT uptake may be influenced by the vagus nerves.


Hyperfunction of neutrophils in a patient with BCR/ABL negative chronic myeloid leukemia: a case report with in vitro studies.
Among patients diagnosed with chronic myeloid leukemia (CML), a small percentage lack a BCR/ABL fusion gene, a landmark of CML. Their clinical features are distinct from patients with BCR/ABL positive CML, although to the authors' knowledge the pathogenesis to date has been unknown. A 50-year-old female patient with BCR/ABL negative CML and multiple complications of Graves disease, Sweet syndrome, and a fatal pulmonary alveolar proteinosis (PAP) is described in the current study. To show a clonal origin of her myeloid cells, hypoxanthine phosphoribosyltransferase (HPRT) assay was applied. Because the patient developed a progressive and fatal neutrophilia, a screening of cell functions in neutrophilic lineage, including in vitro colony assay of her bone marrow cells and production of superoxide and interleukin-8 (IL-8) by blood neutrophils was performed. Southern blot analysis based on the polymorphism of the HPRT gene was compatible with monoclonality of her neutrophils. The patient had an increased amount of bone marrow granulocyte-macrophage progenitor cells, which formed colonies in response to a very low dose (0.1 ng/mL) of granulocyte-colony stimulating factor. In vitro production of superoxide and IL-8, which is an inducer of positive chemotaxis of neutrophils, by her peripheral neutrophils was markedly augmented. Her bronchoalveolar lavage fluid also contained a significant amount of IL-8 as well as an unusual infiltration of neutrophils. In the patient in the current study, hyperfunction of the neutrophils might have contributed to the onset of PAP as well as Sweet syndrome and to the pathogenesis of BCR/ABL negative CML.


Alkaline stress inhibits the growth of Staphylococcus epidermidis by inducing TCA cycle-triggered ROS production.
Many species of bacteria interact on the human skin to form a certain microbiome. Delftia acidovorans, a bacterium detected from human skin, inhibits the growth of S. epidermidis, a dominant bacterium of the human skin microbiota. Here, we show that ammonia secreted by D. acidovorans inhibits the growth of S. epidermidis by increasing the pH value of the medium. The pH value of D. acidovorans culture supernatant (CS) was higher than that of the medium without culture. The inhibitory activity of the D. acidovorans CS against the growth of S. epidermidis was decreased by neutralization with hydrochloric acid. Genes encoding enzymes related to ammonia production were found in the D. acidovorans genome. Moreover, the D. acidovorans CS contained a high concentration of ammonia. The addition of ammonia to S. epidermidis culture led to an increase in the reactive oxygen species (ROS) production and inhibited S. epidermidis growth. The addition of sodium hydroxide also led to an increase in the ROS production and inhibited S. epidermidis growth. The inhibitory activity of ammonia and sodium hydroxide against S. epidermidis growth was suppressed by malonic acid, an inhibitor of succinate dehydrogenase in the tricarboxylic acid (TCA) cycle, and N-acetyl-l-cysteine, a free radical scavenger. These findings suggest that D. acidovorans secretes ammonia and alkaline stress inhibits the growth of S. epidermidis by inducing TCA cycle-triggered ROS production.


Crystal structure of the outer membrane active transporter FepA from Escherichia coli.
Integral outer membrane receptors for iron chelates and vitamin B12 carry out specific ligand transport against a concentration gradient. Energy for active transport is obtained from the proton-motive force of the inner membrane through physical interaction with TonB-ExbB-ExbD, an inner membrane complex. Here we report the crystal structure of an active transport, outer membrane receptor at 2.4 A resolution. Two distinct functional domains are revealed: (i) a 22-stranded beta-barrel that spans the outer membrane and contains large extracellular loops which appear to function in ligand binding; and (ii) a globular N-terminal domain that folds into the barrel pore, inhibiting access to the periplasm and contributing two additional loops for potential ligand binding. These loops could provide a signaling pathway between the processes of ligand recognition and TonB-mediated transport. The blockage of the pore suggests that the N-terminal domain must undergo a conformational rearrangement to allow ligand transport into the periplasm.


Rapid multiplex polymerase chain reaction for detection of mcr-1 to mcr-5 genes.
A rapid (total time <2 h) and reliable multiplex polymerase chain reaction for screening of mcr-1 to mcr-5 genes conferring resistance to colistin has been developed. This technique has been tested on a collection of isolates previously identified as bearing mcr-1, mcr-2, and mcr-like genes and had a sensitivity and a specificity of 100%. Using this method, we were also able to identify a single isolate possessing both mcr-1 and mcr-5 genes.


Effect of prenatal and neonatal pantothenic acid deficiency on rat intestinal phosphatases.
Alkaline phosphatase activity was increased in the distal part of the small intestine of pantothenic acid deficient neonatal rats, while acid phosphatase activity was slightly increased and protein concentration was decreased throughout the small intestine. The growth and maturation of the distal part of the small intestine were retarded more severely than in the proximal part.


AAV6.βARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model.
G protein-coupled receptor kinase 2 (GRK2), which is markedly upregulated in failing human myocardium, has been implicated as a contributing factor or consequence of heart failure (HF). Importantly, cardiac-specific GRK2 knockout mice have recently proved the pathological nature of GRK2 in HF. Targeted inhibition of GRK2 is possible using a peptide inhibitor known as the βARKct, which has rescued several disparate small animal HF models. This study was designed to evaluate long-term βARKct expression in a clinically relevant large animal HF model, using stable myocardial gene delivery with adeno-associated virus serotype 6 (AAV6). A porcine model of HF subsequent to left ventricular (LV) myocardial infarction (MI) was used to study the effects of retrograde injection into the anterior interventricular vein of either AAV6.βARKct or AAV6.luciferase as a control 2 weeks after MI. Echocardiography and LV hemodynamics were performed before and 6 weeks after gene transfer. Robust and long-term βARKct expression was found after AAV6-mediated delivery, leading to significant amelioration of LV haemodynamics and contractile function in HF pigs compared with AAV6.luciferase-treated control animals that showed a continued decline in cardiac function. Interestingly, the neurohormonal axis was virtually normalized in AVV6.βARKct-treated HF animals, represented by reductions in plasma norepinephrine levels, whereas AAV6.luciferase-treated pigs showed further increases in plasma catecholamine levels. As a result, LV remodelling and foetal gene expression was reversed by AVV6.βARKct gene therapy. These data--showing sustained amelioration of cardiac function in a post-MI pig HF model--demonstrate the therapeutic potential of βARKct gene therapy for HF.


miR-455-5p suppresses hepatocellular carcinoma cell growth and invasion via IGF-1R/AKT/GLUT1 pathway by targeting IGF-1R.
Hepatocellular carcinoma (HCC) is among the most frequently observed forms of cancer. MicroRNAs (miRNAs) are increasingly thought to play a key role in regulating the onset and progression of a wide range of cancer types. In the present report, we found that miR-455-5p expression was significantly decreased in both HCC patient tumor tissues and cell lines, and that this reduction in expression was linked to poorer patient outcomes. When we overexpressed miR-455-5p in HCC cell lines (Huh7 and HepG2), this was linked with impaired proliferation, colony formation, migration, and invasion. We further found that this miRNA was able to directly bind the insulin growth factor receptor (IGF-1R) 3'-untranslated region, thereby suppressing IGF-1R expression in HCC cells. Consistent with this, miR-455-5p overexpression was associated with reduced glucose transporter (GLUT) 1 expression, which in turn inhibited HCC cell uptake of glucose, production of lactate, and generation of ATP. Together these results thus indicate that mIR-455-5p is able to suppress tumor functionality via impairing glycolysis in HCC cells, highlighting this miRNA as a potential target for anti-cancer therapeutic interventions.


Bioluminescence imaging to study the promoter activity of hla of Staphylococcus aureus in vitro and in vivo.
Alpha-toxin (Hla, encoded by hla) is a major virulence factor of Staphylococcus aureus. The activity of the hla promoter was analyzed using luxABCDE on an integration vector. The phla-lux construct was introduced in S. aureus Newman and its isogenic sae and sigB regulator mutants. Promoter activity was monitored by bioluminescence in vitro and in the murine tissue-cage model. Hla promoter activity could be followed in real time at repeated time points of infection. The activation of hla in the sigB-deficient strain and the repression to background levels in a sae-deficient strain relative to hla expression in the wild type could be demonstrated in vivo. Subinhibitory concentrations of teicoplanin, imipenem and ciprofloxacin enhanced hla promoter activity in vitro whereas clindamycin and rifampicin did not. Our approach proved to be rapid and adequate to study promoter activity in vitro and in vivo under conditions where high bacterial numbers are reached.


Beta-hairpin formation in aqueous solution and in the presence of trifluoroethanol: a (1)H and (13)C nuclear magnetic resonance conformational study of designed peptides.
In order to check our current knowledge on the principles involved in beta-hairpin formation, we have modified the sequence of a 3:5 beta-hairpin forming peptide with two different purposes, first to increase the stability of the formed 3:5 beta-hairpin, and second to convert the 3:5 beta-hairpin into a 2:2 beta-hairpin. The conformational behavior of the designed peptides was investigated in aqueous solution and in 30% trifluoroethanol (TFE) by analysis of the following nuclear magnetic resonance (NMR) parameters: nuclear Overhauser effect (NOE) data, and C(alpha)H, (13)C(alpha), and (13)C(beta) conformational shifts. From the differences in the ability to adopt beta-hairpin structures in these peptides, we have arrived to the following conclusions: (i) beta-Hairpin population increases with the statistical propensity of residues to occupy each turn position. (ii) The loop length, and in turn, the beta-hairpin type, can be modified as a function of the type of turn favored by the loop sequence. These two conclusions reinforce previous results about the importance of beta-turn sequence in beta-hairpin folding. (iii) Side-chain packing on each face of the beta-sheet may play a major role in beta-hairpin stability; hence simplified analysis in terms of isolated pair interactions and intrinsic beta-sheet propensities is insufficient. (iv) Contributions to beta-hairpin stability of turn and strand sequences are not completely independent. (v) The burial of hydrophobic surface upon beta-hairpin formation that, in turn, depends on side-chain packing also contributes to beta-hairpin stability. (vi) As previously observed, TFE stabilizes beta-hairpin structures, but the extent of the contribution of different factors to beta-hairpin formation is sometimes different in aqueous solution and in 30% TFE.


[Muscarinic acetylcholine receptors of the chick amnion].
The presence of muscarinic (M) acetylcholine receptors in the noninnervated chick amnion makes it possible to analyze their functioning with presynaptic effects excluded. The M receptors of the amnion mediating its contraction were identified by testing with selective antagonists: pirenzepine for M1, methoctramine for M2, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) for M3, and tropicamide for M4 receptor subtype. All antagonists acted as competitive inhibitors of M-acetylcholine receptors. With respect to cholinolytic activity estimated from the response to carbacholine (CBC) (-logIC50), the antagonists could be arranged in the following series: 4-DAMP (8.29) > tropicamide (6.97) > pirenzepine (5.85) > methoctramine (5.63). In addition, the effect of forskolin (5 microM), activator of adenylate cyclase (AC), was unidirectional with beta-adrenergic agonists; it blocked CBC-induced contractile activity of the amnion, whereas phospholipase C (1.25 U/ml) stimulated this activity. These data suggest that CBC- or acetylcholine (ACh)-induced contractile activity of the amnion is mediated by M3 acetylcholine receptors. Evaluation of contractile response to ACh by the tonic component usually revealed one pool of M3 acetylcholine receptors. One pool was also revealed after treatment with 4-DAMP, with the Hill coefficient being increased (ACh, n = 1.07; ACh against the 4-DAMP background, n = 1.48). It is possible to detect two pools of M3-acetylcholine receptors on the basis of either phase-frequency or tonic response, i.e., independently of the test parameter.


Unilateral application of an inflammatory irritant to the rat temporomandibular joint region produces bilateral modulation of the jaw-opening reflex.
The aim of this study was to determine the effect of unilateral acute inflammation of craniofacial deep tissues on the ipsilateral and contralateral jaw-opening reflex (JOR). The effects of mustard oil (MO), injected into the temporomandibular joint region, were tested on the JOR recorded in the digastric muscle and evoked by low-intensity electrical stimulation of the ipsilateral and contralateral inferior alveolar nerve in anesthetized rats. The MO injection induced a long-lasting suppression of the amplitude of both ipsilaterally and contralaterally evoked JOR, although the latency and duration of the JOR were unaffected. The suppressive effect was more prominent for the contralaterally evoked JOR, and observed even when background activity in the digastric muscle was increased by the MO injection. The results indicate that changes in the JOR amplitude following MO injection do not simply reflect alterations in motoneuronal excitability, and suggest that inflammation of deep craniofacial tissues modulates low-threshold sensory transmission to the motoneurons.


Clinical validation of the nursing diagnostic proposition perioperative thirst.
to verify the clinical validity of the proposition of a new nursing diagnosis called perioperative thirst, based on the diagnostic accuracy of its clinical indicators, including the magnitude of effect of its etiological factors. clinical diagnostic validation study with a total of 150 surgical patients at a university hospital. Sociodemographic variables and clinical indicators related to thirst were collected. The latent class analysis technique was used. two models of latent classes were proposed for the defining characteristics. The model adjusted preoperatively included: dry lips, thick saliva, thick tongue, desire to drink water, caregiver report, dry throat and constant swallowing of saliva. In the postoperative period: dry throat, thick saliva, thick tongue, constant swallowing of saliva, desire to drink water, bad taste in the mouth. The factors related to "high ambient temperature" and "dry mouth" are associated with the presence of thirst, as well as the associated conditions "use of anticholinergics" and "intubation". The prevalence of thirst was 62.6% in the pre and 50.2% in the immediate postoperative period. the diagnostic proposition of perioperative thirst showed good accuracy parameters for its clinical indicators and etiological effects. This proposition in a nursing taxonomy will allow greater visibility, appreciation and treatment of this symptom.(1) Evaluates the accuracy of the proposition of the nursing diagnosis perioperative thirst; (2) Allows refined diagnosis for use in clinical practice, teaching and research; (3) Strengthens the systematization of perioperative nursing care; (4) Highlights thirst management as part of care, considering its high prevalence and discomfort; (5) Presents a structure with good accuracy parameters which are representative of thirst.


Correlation between high-performance liquid chromatography and automated fluorimetric methods for the determination of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid in nervous tissue and cerebrospinal fluid.
The correlation between automated fluorimetric methods and high-performance liquid chromatography is described for the determination of homovanillic acid and 5-hydroxyindoleacetic acid in cerebrospinal fluid, and for dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in striata of rat brain. The automated fluorimetric methods for 3,4-dihydroxyphenylacetic acid and homovanillic acid showed a good correlation with the high-performance liquid chromatographic methodology. The fluorimetric determination for dopamine was somewhat less reliable than the high-performance liquid chromatographic assay. The fluorimetric assay for 5-hydroxyindoleacetic acid correlated poorly with the chromatographic method.


Targeting KNDy neurons to control GnRH pulses.
Gonadotropin-releasing hormone (GnRH) is the final output of the central nervous system that drives fertility. A characteristic of GnRH secretion is its pulsatility, which is driven by a pulse generator. Each GnRH pulse triggers a luteinizing hormone (LH) pulse. However, the puzzle has been to reconcile the synchronicity of GnRH neurons with the scattered hypothalamic distribution of their cell bodies. A leap toward understanding GnRH pulses was the discovery of kisspeptin neurons near the distal processes of GnRH neurons, which secrete kisspeptins, potent excitatory neuropeptides on GnRH neurons, and equipped with dual, but opposite, self-modulatory neuropeptides, neurokinin B and dynorphin. Over the last decade, this cell-to-cell communication has been dissected in animal models. Today the 50-year quest for the basic mechanism of GnRH pulse generation may be over, but questions about its physiological tuning remain. Here is an overview of recent basic research that frames translational research.


Periodontal and cardiovascular therapies modify specialized pro-resolving lipid mediator (sPRLM) (LPXA4, PD1, RvE1, RvD1, and MaR1)-mediated pathway: the first pilot clinical study.
Cardiovascular disease (CVD) and periodontal disease have a common pathogenesis with inflammation and resolution steps. Although the relationships among periodontal disease, CVD, and specialized pro-resolving lipid mediator (sPRLM)s are well known, there is no study about the combined effects of cardiovascular and periodontal treatments on sPRLM levels. It was aimed to evaluate the effects of periodontal and cardiovascular therapies on sPRLMs (lipoxin A4, protectin (PD)1, resolvin (Rv) E1, RvD1, and maresin (MaR)1) in patients with CVD and periodontal disease. This observational study consisted of fifty-five patients with CVD and mild or moderate periodontitis. The clinical periodontal parameters (plaque index, gingival index, probing pocket depth, percentage of bleeding on probing, and clinical attachment level) and blood and unstimulated total saliva samples were obtained at baseline, at 3 months (following only cardiovascular therapy), and at 6 months (following cardiovascular and periodontal therapies). The blood count and serum levels of cardiometabolic biomarkers (white blood cell, neutrophil/lymphocyte, serum total cholesterol (TC), triglyceride, and low and high-density lipoprotein (HDL) levels) were evaluated. sPRLMs were evaluated by ELISA. There were significant decreases in body mass index, clinical periodontal parameters, WBC, LDL, PD1, and RvD1 at 6 months compared to baseline. The decreases in TC/HDL, RvE1, and MaR1 levels were significant at 3 and 6 months compared to baseline (p < 0.05). The combination of cardiovascular and periodontal treatments leads to significant reductions in clinical periodontal and cardiometabolic parameters and sPRLMs. Our report, which is the first in their field, suggested that cardiovascular and periodontal therapies provide an important contribution via decreasing the periodontal and atherosclerotic inflammation modulating sPRLMs. This finding will be a big step toward increasing the quality of life in these patients by drawing attention to importance of public health associated with oral hygiene, periodontal health, and systemic phase of periodontal treatment.


Soluble DNAM-1, as a Predictive Biomarker for Acute Graft-Versus-Host Disease.
Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because diagnosis of aGVHD is exclusively based on clinical symptoms and pathological findings, reliable and noninvasive laboratory tests for accurate diagnosis are required. An activating immunoreceptor, DNAM-1 (CD226), is expressed on T cells and natural killer cells and is involved in the development of aGVHD. Here, we identified a soluble form of DNAM-1 (sDNAM-1) in human sera. In retrospective univariate and multivariate analyses of allo-HSCT patients (n = 71) at a single center, cumulative incidences of all grade (grade I-IV) and sgrade II-IV aGVHD in patients with high maximal serum levels of sDNAM-1 (≥30 pM) in the 7 days before allo-HSCT were significantly higher than those in patients with low maximal serum levels of sDNAM-1 (<30 pM) in the same period. However, sDNAM-1 was not associated with other known allo-HSCT complications. Our data suggest that sDNAM-1 is potentially a unique candidate as a predictive biomarker for the development of aGVHD.


Suppression of food intake in rats by fluoxetine: comparison of enantiomers and effects of serotonin antagonists.
R- and S-enantiomers of fluoxetine lowered food intake in meal-fed rats and in 2-deoxyglucose-induced hyperphagic rats. In both feeding paradigms, the S-enantiomer was slightly more potent. The potency of the two enantiomers of fluoxetine in producing anorectic effects paralleled their potency as inhibitors of 5-hydroxytryptamine (5HT) uptake in vivo. Both enantiomers were selective inhibitors of 5HT uptake in vitro and showed only weak affinity for 5HT-1, 5HT-1A and 5HT-2 receptors or for other receptors in rat brain. The anorectic effect of fluoxetine in meal-fed rats was not reversed by either centrally or peripherally acting 5HT-2 receptor antagonists (ritanserin, LY53857, xylamidine, BW 501C67) or a nonspecific 5HT receptor antagonist, metergoline. However, the serotonergic mechanism involved in the anorexic effect of fluoxetine is discussed.


Coordinated regulation of endothelial and fibroblast cell proliferation and matrix synthesis in periodontal ligament adjacent to appositional and resorptive bone surfaces.
Little is known about the remodeling of blood vessels and soft connective tissue or the proliferation of endothelial cells in the periodontal ligament (PL) of teeth undergoing physiological drift. To determine whether there is evidence for coordinated regulation of endothelial cell and fibroblast proliferation and matrix synthesis in sites within the PL adjacent to bone-appositional (A) and bone-resorptive (R) surfaces, the PL in mouse mandibular molar was subdivided into A and R sectors on the basis of 3H-proline incorporation into alveolar bone. Computer-assisted morphometry of radioautographs showed that the number and area of blood vessels were similar in A and R sectors. Proliferation of endothelial cells and fibroblasts was assessed from radioautographs prepared from mice continuously labeled with 3H-thymidine at times between 2 and 60 days. Significantly more labeled endothelial cells (P less than .001) and fibroblasts (P less than .05) were seen in the A sector. The percent of labeled endothelial cells and the percent of labeled fibroblasts increased linearly to 25 days and then formed a plateau. The rate of increase of labeled fibroblasts was higher in the A sector than in the R sector (P less than .025). In addition, 3H-proline grain counts over extracellular matrix were significantly higher in the appositional sector than in the resorptive sector (P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)


Congenital prepubic sinus presenting with purulent discharge after circumcision: a case report.
Congenital prepubic sinus is a rare anomaly found in the midline of the lower abdomen. Congenital prepubic sinus is usually asymptomatic in neonates, and a diagnosis is often achieved later in life after spontaneous extrusion of purulent material from the pre-existing hole in the pubic region. We present a case of congenital prepubic sinus presenting with purulent discharge after circumcision. A 4-year-old Caucasian boy presented to our urology out-patient clinic with purulent discharge from the distal part of the dorsum of his penis. He had a history of circumcision performed at a different center, 6 months ago. His parents stated that although various antibiotics were used, the purulent discharge continued for 6 months and the child had no complaints before circumcision. His condition was reported as superficial dorsal venous thrombosis, known as penile Mondor disease, in magnetic resonance imaging that was performed in the previous hospital. A physical examination revealed a small pinhole lesion at the distal part of his penis and a rigid cylindrical tube extending to the proximal side of his penis. We performed fistulography by injecting contrast material through a small angiocatheter and confirmed the diagnosis of prepubic sinus. Surgical exploration was performed and a long sinus, apparently ending as a fibrous tract at the anterior surface of his pubic symphysis, was found and resected. Before congenital prepubic sinus surgery, it is critically important to rule out penile Mondor disease and the possibility of a circumcision complication (especially infective complications) mimicking congenital prepubic sinus.


Single Dose Steroid Injection After Loss of Signal (LOS) During Thyroid Surgery is Effective to Recover Electric Signal Avoiding Vocal Cord Palsy and the Need of Staged Thyroidectomy: Prospective Evaluation on 702 Patients.
Steroids are often used for the management of vocal cord palsy after thyroid surgery. There are no reports in the current literature of their intraoperative use, immediately after a loss of signal during neuromonitoring (LOS). We evaluate the impact of a single dose of 4 mg of dexamethasone on laryngeal nerve function, administrated at the time of a LOS during a nerve-monitored thyroidectomy. A prospective not randomized study was performed, dividing patients in two groups, when a LOS was detected. LOS was defined as an electromyographic signal (EMG) inferior to 100 μV when stimulating the inferior laryngeal nerve, according to international guidelines. In group 1 (G1), surgeon waits for signal's recovery up to 20 min. Absence of a detectable signal after 20 min was predictive of vocal cord palsy; if it affected the first side of surgery the procedure was interrupted to avoid the risk of bilateral nerve palsy. In group 2 (G2), 4 mg of dexamethasone were injected within 10 min from a detected LOS, waiting 10 min for its effects. An EMG value > to 200 μV within 20' after steroid administration was predictive of full recovery and normal post-operatory vocal cord function. Vocal cords motility was checked at postoperative day 1 in all patients by an experienced ENT. Between January 2017 and December 2018, 702 patients underwent thyroid surgery under intermittent intraoperative nerve monitoring by two expert surgeons. A LOS was found in 22 patients in G1 and 16 in G2. Four patients in G1 spontaneously recovered electric signal (18.2%), while in G2 a signal was recovered in 14/16 patients (87.5%) (p < 0.001). This immediate effect was monitored by EMG, showing the increase in potentials at 10, 15 and 20 min after injection. ENT evaluation found vocal cord palsy, respectively, in 18/22 and 1/16 patients (G1 vs G2, p < 0.001). One of the patients in G2 who recovered electric signal presented transient palsy, fully recovered at 2 months, while the two patients who had a signal < 200 μV did not present postoperative cord palsy. In G1, 10/18 palsy were definitive. No permanent palsies were presents in G2. A single 4 mg iv dexamethasone injection within 10 min form a LOS during thyroid surgery exerts a therapeutic action, measurable by EMG modifications. It avoids vocal nerve palsy and the need of a staged thyroidectomy. It may also protect from permanent cord palsy, but the mechanism is unknown.


The Role of PPARgamma in pulmonary vascular disease.
The peroxisome proliferator-activated receptor (PPAR) gamma is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Thiazolidinediones, pharmacological ligands for PPARgamma, are currently used in the management of type 2 diabetes. Peroxisome proliferator-activated receptor gamma is expressed in the lung and pulmonary vasculature, and its expression is reduced in the vascular lesions of patients with pulmonary hypertension. Furthermore, thiazolidinedione PPARgamma ligands reduced pulmonary hypertension and vascular remodeling in several experimental models of pulmonary hypertension. This report reviews current evidence that PPARgamma may represent a novel therapeutic target in pulmonary hypertension and examines studies that have begun to elucidate mechanisms that underlie these potential therapeutic effects.


Expressed sequence tags from the red imported fire ant, Solenopsis invicta: annotation and utilization for discovery of viruses.
An expression library was created and 2304 clones sequenced from a monogyne colony of Solenopsis invicta. The primary intention of the project was to utilize homologous gene identification to facilitate discovery of viruses infecting this ant pest that could potentially be used in pest management. Additional genes were identified from the ant host and associated pathogens that serve as an important resource for studying these organisms. After assembly and removal of mitochondrial and poor quality sequences, 1054 unique sequences were yielded and deposited into the GenBank database under Accession Nos. EH412746 through EH413799. At least nine expressed sequence tags (ESTs) were identified as possessing microsatellite motifs and 15 ESTs exhibited significant homology with microsporidian genes. These sequences most likely originated from Thelohania solenopsae, a well-characterized microsporidian that infects S. invicta. Six ESTs exhibited significant homology with single-stranded RNA viruses (3B4, 3F6, 11F1, 12G12, 14D5, and 24C10). Subsequent analysis of these putative viral ESTs revealed that 3B4 was most likely a ribosomal gene of S. invicta, 11F1 was a single-stranded RNA (ssRNA) virus contaminant introduced into the colony from the cricket food source, 12G12 appeared to be a plant-infecting tenuivirus also introduced into the colony as a field contaminant, and 3F6, 14D5, and 24C10 were all from a unique ssRNA virus found to infect S. invicta. The sequencing project illustrates the utility of this method for discovery of viruses and pathogens that may otherwise go undiscovered.


Assessing the patient with a skin condition.
Skin diseases affect 20-30% of the population at any one time, seriously interfering with activities in 10%. Skin conditions are, by their vary nature, visible. As a result, those with a skin condition receive the same reaction from society as anyone who looks 'different'. They can be subjected to stares, whispered comments, antagonism, insult or exclusion from normal social activity. Those with a skin condition have the needs of all other patients, but in addition, the impact upon their lives of a skin condition, its treatment and the ways in which others perceive them, makes their situation unique. Many nurses however will have little or no experience of patients with skin conditions. They need therefore to be aware of the wide-ranging effects skin disease can have on the individual and their family. It is important that nurses understand the basic principles of skin disease and care, but are also aware of their limitations, seeking further advice as necessary. This article will guide the nurse in assessing patients with a skin condition.


Traumatic posterior sternoclavicular joint dislocation - Current aspects of management.
The posterior sternoclavicular joint dislocation is a rare and potentially life-threatening injury, as massive haemorrhage can occur at the time of trauma, during reduction manoeuvres and drilling. These injuries are rare and a collective experience of managing them is of paramount importance. We present our multidisciplinary experience of managing several of these injuries in our centre, with learning points we have identified. Assessment should include Computerised Tomography Angiography (CTA) to assess the anatomy of the joint including the proximity to the underlying innominate vein and to identify any bleeding. Both closed reduction and open reconstruction have the potential for massive haemorrhage which can be controlled successfully with direct access to the underlying vessel. We recommend that all reductions should be performed in the presence of a cardiothoracic surgeon who can gain vascular control in the head, neck, and thorax. In specific high-risk cases, pre-emptive venous catheterisation can also be considered. We recommend that a discussion and rehearsal for intra-operative bleeding should be undertaken with the whole theatre team, with roles assigned pre-emptively and to allow identification of any deficiencies in staff expertise or equipment. Of the five recent cases managed in our centre one patient had a closed reduction and four had open reductions. Success of closed reductions within 48 h is high and these can be attempted up to 10 days after injury. Our patient undergoing closed reduction had a favourable outcome and returned to professional rugby at five months. Open reduction was performed in a physeal fracture as there was a delay to surgery and callus had begun to form and had the potential to adhere to the underlying vessel. In this case we performed open reduction and stabilised with tunnelled suture fixation. Our preferred method of reconstruction uses a palmaris graft with internal figure of eight bracing. One patient had a subsequent fracture of the medial clavicle around the drill holes that healed without further intervention. Despite good reduction and stability achieved following palmaris reconstructions, two patients are experiencing ongoing symptoms of globus and one with voice change without any objective underlying cause.


Comparison of vessel wall morphologic appearance at sites of focal and diffuse coronary vasospasm by intravascular ultrasound.
Coronary vasospasm is manifested by either focal or diffuse pattern in clinical settings. To examine the differences in vessel wall morphologic appearance between the sites of focal and diffuse vasospasm, we studied 29 patients with chest pain at rest, during exertion, or both by intravascular ultrasound. By angiography, focal vasospasm with diameter reduction of 90% +/- 3% (mean +/- SD) was provoked by intracoronary ergonovine (0.01 to 0.04 mg) in 15 patients. Diffuse vasospasm with diameter reduction of 79% +/- 5% (NS) was provoked in seven patients, and the remaining seven patients served as the control group. By ultrasonography, a significantly thickened intimal leading edge with sonolucent zone was observed in 55 sites from 22 coronary arteries with either focal or diffuse vasospasms (0.61 +/- 0.32 mm), although these sites were normal or minimally narrowed by angiography. Seven segments from the control group exhibited a thin intimal leading edge with sonolucent zone (0.23 +/- 0.08 mm, p < 0.01). When the thickness of the intimal leading edge with sonolucent zone was compared between the abnormal sites with focal and diffuse vasospasm, this was significantly greater at focal spasm, 1.01 +/- 0.35 mm (n = 15), than that at diffuse spasm, 0.46 +/- 0.13 mm (n = 40, p < 0.01). At the sites with diffuse spasm, some of the lesions lay scattered along the coronary vessels, although the lesions were localized at the sites of focal vasospasm. These results indicate that atherosclerosis is present at sites with both focal and diffuse vasospasm even in the absence of angiographically significant coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease-Associated Abdominal Aortic Aneurysm.
Kawasaki disease (KD) is the most common cause of acquired cardiac disease in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated the development of systemic arterial dilatation and aneurysms, including abdominal aortic aneurysm (AAA) in the Lactobacillus casei cell-wall extract (LCWE)-induced KD vasculitis mouse model. We discovered that in addition to aortitis, coronary arteritis and myocarditis, the LCWE-induced KD mouse model is also associated with abdominal aorta dilatation and AAA, as well as renal and iliac artery aneurysms. AAA induced in KD mice was exclusively infrarenal, both fusiform and saccular, with intimal proliferation, myofibroblastic proliferation, break in the elastin layer, vascular smooth muscle cell loss, and inflammatory cell accumulation in the media and adventitia. Il1r(-/-), Il1a(-/-), and Il1b(-/-) mice were protected from KD associated AAA. Infiltrating CD11c(+) macrophages produced active caspase-1, and caspase-1 or NLRP3 deficiency inhibited AAA formation. Treatment with interleukin (IL)-1R antagonist (Anakinra), anti-IL-1α, or anti-IL-1β mAb blocked LCWE-induced AAA formation. Similar to clinical KD, the LCWE-induced KD vasculitis mouse model can also be accompanied by AAA formation. Both IL-1α and IL-1β play a key role, and use of an IL-1R blocking agent that inhibits both pathways may be a promising therapeutic target not only for KD coronary arteritis, but also for the other systemic arterial aneurysms including AAA that maybe seen in severe cases of KD. The LCWE-induced vasculitis model may also represent an alternative model for AAA disease.


[Use of cell cultures in the pharmacological experiment].
A statistical method is proposed which makes it possible to evaluate quantitatively the significance and reliability of the effects of pharmacological agents during their study on cell cultures using a little scope of material samples. The method substantially reduces the expenditures of the researcher's time and labour.


Discordant effects of beta-blockade on central aortic systolic and brachial systolic blood pressure: considerations beyond the cuff.
The role of beta-blockers in uncomplicated hypertension has been challenged recently. Compared with other antihypertensives, beta-blockers are less effective for preventing cardiovascular events in patients with uncomplicated hypertension. Moreover, a recent meta-analysis of placebo-controlled clinical trials concluded that atenolol is not more efficacious than placebo for preventing cardiovascular events in patients with hypertension. Although these agents lower blood pressure measured conventionally over the brachial artery with a blood pressure cuff, they do not exert a commensurate effect on blood pressure in the central aorta. Central aortic blood pressure and aortic augmentation index are strong predictors of left ventricular hypertrophy, an independent risk factor for cardiovascular events. Emerging data are illuminating the antihypertensive paradox whereby antihypertensive agents may elicit discordant effects on central and peripheral blood pressure and hemodynamics. Vasodilatory antihypertensives, such as renin-angiotensin-aldosterone system inhibitors and calcium channel blockers, elicit reductions in central aortic blood pressure equal to or greater than that in the brachial artery. Conversely, beta-blockers lower central aortic blood pressure to a lesser degree even when blood pressure measured by sphygmomanometry is reduced substantially. Given the strong relationship between central aortic blood pressure and target organ damage, the effectiveness of beta-blockers may be overestimated in practice on the basis of conventional blood pressure measurements alone. Differences in central and peripheral blood pressure may account for the lack of cardiovascular protection afforded by beta-blockers in clinical trials and could account for a portion of the apparent "benefit beyond blood pressure" reduction with other classes of antihypertensive agents. Future studies should aim to better clarify the role of central aortic blood pressure in the treatment of hypertension. In the meantime, the effects of antihypertensive drugs on blood pressure "beyond the brachial blood pressure cuff" should be considered when prescribing antihypertensive agents for a patient.


Randomized, controlled trial promotes physical activity and reduces consumption of sweets and sodium among overweight and obese adults.
The present study sought to assess the impact of an intervention to reduce weight and control risk factors of noncommunicable chronic diseases in overweight or obese adults who are users of primary and secondary healthcare units of the public health system of Pelotas, Brazil. We hypothesized that individuals who received an educational intervention regarding how to lose weight and prevent other noncommunicable chronic disease risk factors through nutrition would lose weight and acquire active habits during leisure time more frequently than individuals under regular care. Two hundred forty-one participants from the Nutrition Outpatient Clinic of the Medical Teaching Hospital of the Federal University of Pelotas, Brazil, aged 20 years or older and classified as overweight or obese were randomly allocated to either the intervention group (IG; n = 120) or control group (CG; n = 121). The IG received individualized nutritional care for 6 months, and the CG received individualized usual care of the health services. Intention-to-treat analyses showed that at 6 months, mean fasting glycemia and daily consumption of sweet foods and sodium were reduced, and the time spent on physical leisure activity was increased in IG. Analysis of adherence to the protocol of the study revealed that individuals from IG had lost more in body weight, waist circumference, and fasting glucose compared to the CG. Leisure time physical activity increased in IG. Individuals adhered equally to the dietetic recommendations, irrespective of the nutrition approach that was used.


[Single nucleotide polymorphisms in CAPN10 gene of Chinese population and its correlation with type 2 diabetes mellitus in Han people of northern China].
To investigate the distribution of the single nucleotide polymorphisms (SNPs) in CAPN10 gene in Chinese population and their relation with type 2 diabetes mellitus in Han people of Northern China. CAPN10 gene was sequenced to detect SNPs in 27 samples of different nationalities in China. 5 SNPs were genotyped with single-base extension (SBE) method to perform case-control study in 156 normal Han people of Northern China and 173 type 2 diabetes and the 3 positive loci reported in the article were performed haplotype analysis. One positive locus was also analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 68 type 2 diabetes pedigrees (377 cases). A total of 40 SNPs were identified in length of 8,936 bp, with an average of 1 in every 223 bp; The SNPs in CAPN10 gene did not distribute evenly and the SNPs in Chinese was different from that reported in American Mexicans. There was no significantly statistical difference in the allele frequency of the 5 SNPs between case and control (P > 0.05), and the haplotype frequencies in the two groups were not much different (P > 0.05). There was no positive results in TDT and STDT analysis (P > 0.05). The SNP distribution of CAPN10 gene varies with different nationalities. The studied SNPs in CAPN10 gene may not be the major susceptibility ones of type 2 diabetes mellitus in Han people of Northern China.


Transport of cholesterol autoxidation products in rabbit lipoproteins.
Radiolabeled pure [4-14C]cholesterol was kept at 60 degrees C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24, and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractionated by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3 beta,5 alpha,6 beta-triol, 7 alpha- and 7 beta-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products.


Alignment of myoblasts on ultrafine gratings inhibits fusion in vitro.
During development, skeletal muscle precursor cells fuse to form multi-nucleated myotubes. However, it is unclear how this fusion is regulated such that linear myotubes are produced. In a previous study, we found that linear arrays of myoblasts cultured on micropatterns of laminin fused to form linear myotubes of a constant diameter, independent of the width of the laminin track. This suggested that a mechanism exists to prevent myoblasts from fusing laterally [Exp. Cell Res. 230 (1997) 275]. In this study, we have investigated this further by culturing myoblasts on ultrafine grooved surfaces previously shown to align fibroblasts and epithelial cells. We found that all the individual myoblasts were highly aligned along the groove axis, and time-lapse recordings showed that motility was mostly restricted to a direction parallel to the grooves. In contrast to the previous study, however, there was a strong tendency for early differentiating cells to form aggregates either at an angle of approximately 45 degrees or perpendicular to the groove axis. Nevertheless, we rarely saw myotubes formed at those angles, supporting our earlier idea that the ability of cells to fuse laterally is prohibited. Our data strongly suggest that myoblasts are most likely to fuse in an end-to-end configuration, and it is this that enables them to form linear, rather than irregular myotubes.


The effect of interventions on flat and inverted nipple on breastfeeding: A systematic review.
Some methods have been developed to solve flat and/or inverted nipple problems. This study aimed to examine the effects of flat and/or inverted nipple interventions on nipples and breastfeeding. Before initiating the review, the protocol was registered in the 'PROSPERO' database. This study was based on the PRISMA-P guideline. Seven databases (Web of Science, PubMed, ScienceDirect, Scopus, The Cochrane Library, TÜBİTAK Ulakbim and Google Scholar) were searched, and nine studies were included in this review. Hoffman's exercise, the inverted syringe method, and the nipple exercise was quite effective in increasing breastfeeding success. The rate of exclusive breastfeeding in the first, third, and sixth months of mothers followed up with postpartum multidimensional visits was found to be significantly higher in the intervention group than in the control group (p < 0.05). A study in which a rubber band was applied with the help of an injector on flat and inverted nipples showed that 63% of mothers on the third day and all of them in the first month were able to breastfeed without a rubber band. Hoffman's exercise, the inverted syringe technique, and rubber bands corrected the flat and/or inverted nipple. There were studies reporting complications as a result of nipple interventions. It is necessary to disseminate the information that breastfeeding of mothers with flat and/or inverted nipples can be sustained with various interventions. Furthermore, it is believed that providing mothers with a chance to choose the interventions, and thus, the compliance of mothers to the intervention with the method of their choice may increase the success of the intervention.


Equivalency of human menopausal gonadotropin and follicle-stimulating hormone stimulation after gonadotropin-releasing hormone agonist suppression.
This study compares the use of human menopausal gonadotropin (hMG) versus follicle-stimulating hormone (FSH), after gonadotropin-releasing hormone agonist (GnRH-a) suppression for in vitro fertilization. Thirty-seven patients were randomized to ovarian stimulation with either hMG or pure FSH. The GnRH-a leuprolide acetate was administered to all patients beginning in the midluteal phase of the prior cycle and continuing until the day of human chorionic gonadotropin (hCG) administration. There were no significant differences between hMG and FSH cycles with regard to the day of hCG administration, mean peak estradiol levels, number of ampules of medication used, and number of oocytes aspirated, embryos transferred, or pregnancies. We conclude that there is no significant difference between hMG and FSH stimulation when used in conjunction with GnRH-a.


Diabetes-induced changes in lens antioxidant status, glucose utilization and energy metabolism: effect of DL-alpha-lipoic acid.
The study was aimed at evaluating changes in lens antioxidant status, glucose utilization, redox state of free cytosolic NAD(P)-couples and adenine nucleotides in rats with 6-week streptozotocin-induced diabetes, and to assess a possibility of preventing them by DL-alpha-lipoic acid. Rats were divided into control and diabetic groups treated with and without DL-alpha-lipoic acid (100 mg x kg body weight(-1) x day(-1), i.p.). The concentrations of glucose, sorbitol, fructose, myo-inositol, oxidized glutathione, glycolytic intermediates, malate, alpha-glycerophosphate, and adenine nucleotides were assayed in individual lenses spectrofluorometrically by enzymatic methods, reduced glutathione and ascorbate--colorimetrically, and taurine by HPLC. Free cytosolic NAD+:NADH and NADP+:NADPH ratios were calculated from the lactate dehydrogenase and malic enzyme systems. Sorbitol pathway metabolites were found to increase, and antioxidant concentrations were reduced in diabetic rats compared with controls. The profile of glycolytic intermediates (increase in glucose 6-phosphate and fructose 6-phosphate, decrease in fructosel,6-diphosphate, increase in dihydroxyacetone phosphate, 3-phosphoglycerate, phosphoenolpyruvate, pyruvate, and no change in lactate), and 5.9-fold increase in alpha-glycerophosphate suggest diabetes-induced inhibition of glycolysis. Free cytosolic NAD+:NADH ratios, ATP levels, ATP/ADP x inorganic phosphate (Pi), and adenylate charge were reduced in diabetic rats while free cytosolic NADP+:NADPH ratios were elevated. Diabetes-induced changes in the concentrations of antioxidants, key glycolytic intermediates, free cytosolic NAD+:NADH ratios, and energy status were partially prevented by DL-alpha-lipoic acid, while sorbitol pathway metabolites and free cytosolic NADP+:NADPH ratios remained unaffected. In conclusion, diabetes-induced impairment of lens antioxidative defense, glucose intermediary metabolism via glycolysis, energy status and redox changes are partially prevented by DL-alpha-lipoic acid. The findings support the important role of oxidative stress in lens metabolic imbalances in diabetes.


Amelioration of retinal degeneration and proteolysis in acute ocular hypertensive rats by calpain inhibitor ((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester.
Our recent study suggested involvement of calpain-induced proteolysis in retinal degeneration and dysfunction in acute ocular hypertensive rats. The purpose of the present study was to determine if an orally available form of calpain inhibitor, ((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), ameliorated retinal degeneration induced by acute hypertension in rats. To help extrapolate the effect of SNJ-1945 from the rat model to the human glaucomatous patient, in vitro inhibition of calpain-induced proteolysis by SNJ-1945 in monkey and human retinal proteins was compared with proteolysis in rat proteins. Intraocular pressure (IOP) in rats was elevated to 110 mm Hg for 50 min. SNJ-1945 was administrated i.p. or orally before ocular hypertension. Retinal degeneration was evaluated by hematoxylin and eosin (H&E) staining and cell counting. Transcripts for calpains and calpastatin in rat, monkey, and human retinas were measured by quantitative RT-PCR. Calpain activities were determined by casein zymography. Soluble retinal proteins from rat, monkey, and humans were incubated with calcium to activate calpains, with or without SNJ-1945. Proteolysis of calpain substrate alpha-spectrin was analyzed by immunoblotting. Elevated IOP caused retinal degeneration and proteolysis of alpha-spectrin. Both i.p. and oral administration of SNJ-1945 inhibited proteolysis of alpha-spectrin and ameliorated retinal degeneration. Transcript levels for calpain 1 and calpastatin were similar in rat, monkey, and human retinas. Calpain 2 transcript levels were higher in rats compared with monkey and human. Appreciable caseinolytic activities due to calpains were observed in monkey and human retinas. Incubation of retinal soluble proteins with calcium led to proteolysis of alpha-spectrin due to calpains in rat, monkey, and human samples. SNJ-1945 similarly inhibited proteolysis in all species. Our results suggested that orally available calpain inhibitor SNJ-1945 might be a possible candidate drug for testing in preventing progression of glaucomatous retinal degeneration.


Kyphoplasty for the treatment of pain distant to osteoporotic thoracolumbar compressive fractures.
Vertebral fractures are one of the most common osteoporotic fractures. We sought to investigate the incidence of distant pain after osteoporotic vertebral compressive fracture (OVCF) at the thoracolumbar junction, and to explore the effect of kyphoplasty in the treatment of distant pain post-OVCF. Eighty-seven patients diagnosed OVCF between T11 and L2 were included in the study. The region of pain and its proximity to the thoracolumbar compressive fracture was recorded. For pain management, all patients received kyphoplasty. The follow-up period was every 3 months for 1-year post-surgery. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) were used pre-operatively, post-operatively, and at 3-, 6-, and 12-month follow-ups to assess patient status. All patients completed the operation, with 72 patients having focal pain over the compression fracture. Eleven cases also had pain distal to the fracture region in the following areas: lower back, near the iliac crest (n = 6), the groin (n = 3), and the trochanteric region (n = 2). Four cases had pain in distant to the fracture: lower back, near iliac crest (n = 3), and the trochanteric region (n = 1). All patients had a significant improvement in clinical symptoms. The average VAS and the ODI decreased significantly pre-operatively to post-operatively (p < 0.05). In addition to focal tenderness, many patients with thoracolumbar compression fractures may have pain distant to the fracture. This can be successfully treated using kyphoplasty. This phenomenon also indicates that patients at risk of osteoporosis who also have lower back pain should not neglect the potential for a thoracolumbar fracture.


CT angiography of coronary artery aneurysms: detection, definition, causes, and treatment.
This article reviews the predisposing conditions, diagnostic criteria, CT appearances, and potential complications of coronary artery aneurysms. With the increasing use of MDCT to image the coronary arteries, aneurysms will be identified more frequently. Coronary artery aneurysms arise from a variety of causes, with CT appearance, management, and clinical course depending on the cause.


Meckel's diverticulum complicated with gastro-intestinal stromal tumor: Case report.
Meckel's diverticulum is a common congenital anomaly, mostly asymptomatic. Tumors may arise rarely in these diverticulae. We claim presenting a new problem to the medical staff in Egypt. We report a case of a 49year old male patient who attended our center with pelvic mass insinuated between the bladder and the rectum. On exploration the mass was found arising at the tip of a Meckel's diverticulum, Gastro-intestinal stromal tumor (GIST) was confirmed by pathology. In review of recently published cases most of these tumors were presented with vague abdominal pain as in our case. Tumors were treated by resection with or without adjuvant Imatinib. Surgeons and oncologists should bear in mind this rare diagnosis and know how to treat it.


Predictive Factors of Response to Immunotherapy in Lymphomas: A Multicentre Clinical Data Warehouse Study (PRONOSTIM).
Immunotherapy (IT) is a major therapeutic strategy for lymphoma, significantly improving patient prognosis. IT remains ineffective for a significant number of patients, however, and exposes them to specific toxicities. The identification predictive factors around efficacy and toxicity would allow better targeting of patients with a higher ratio of benefit to risk. PRONOSTIM is a multicenter and retrospective study using the Clinical Data Warehouse (CDW) of the Greater Paris University Hospitals network. Adult patients with Hodgkin lymphoma or diffuse large-cell B lymphoma treated with immune checkpoint inhibitors or CAR T (Chimeric antigen receptor T) cells between 2017 and 2022 were included. Analysis of covariates influencing progression-free survival (PFS) or the occurrence of grade ≥3 toxicity was performed. In total, 249 patients were included. From this study, already known predictors for response or toxicity of CAR T cells such as age, elevated lactate dehydrogenase, and elevated C-Reactive Protein at the time of infusion were confirmed. In addition, male gender, low hemoglobin, and hypo- or hyperkalemia were demonstrated to be potential predictive factors for progression after CAR T cell therapy. These findings prove the attractiveness of CDW in generating real-world data, and show its essential contribution to identifying new predictors for decision support before starting IT.


A psychometric evaluation of the Hospital Anxiety and Depression Scale in patients diagnosed with end-stage renal disease.
To determine the psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in patients with end-stage renal disease (ESRD) and determine the suitability of the instrument for use with this clinical group. Between-subjects and cross-sectional design. The independent variable was type of treatment for ESRD. The dependent variables were HADS total (all items) and HADS anxiety and depression subscale scores. Group differences in HADS scores were determined using between-subjects one-way analysis of variance (ANOVA). Exploratory and confirmatory factor analyses were conducted on the HADS to determine its psychometric properties in 160 patients with ESRD. Seven models were tested to determine model fit to the data. None of the seven models tested proved to be an adequate fit to the data. Treatment modality was found to have a significant impact on HADS-assessed levels of anxiety and depression. CONCLSIONS: The clinical utility of the HADS in the assessment of anxiety and depression in ESRD patients may be enhanced by using the HADS total (all items) score as an index of psychological distress. Further research is required to establish the appropriateness of using the HADS to screen ESRD patients.


Spatiotemporal signalling in plant development.
Plants, being sessile organisms, need to respond to changing environments, and as a result they have evolved unique signalling mechanisms that allow rapid communication between different parts of the plant. The signalling mechanisms that direct plant development include long-range effectors, such as phytohormones, and molecules with a local intra-organ range, such as peptides, transcription factors and some small RNAs. In this Review, we highlight recent advances in understanding plant signalling mechanisms and discuss how different classes of signalling networks can integrate with gene regulatory networks and contribute to plant development. In some cases, we also address the evolutionary context of mechanisms and discuss possible links between the lifestyle of plants and selection for different signalling mechanisms.


Supporting new graduate physiotherapists in their first year of private practice with a structured professional development program; a qualitative study.
The transition from physiotherapy student to working in private practice has been identified as challenging. However, very little is known about whether structured professional development programs impact on this transition. To describe new graduates' perceptions of a structured professional development program, termed the Recent Graduate Program (RGP), designed to support their transition into physiotherapy private practice. Qualitative analysis of data from a one-year longitudinal mixed methods study. A total of 72 interviews were conducted over a one-year period with 20 new graduates from 19 private practices within one publicly listed allied health organisation. Semi-structured interviews were conducted before commencing work and at three, nine and 12 months. Interviews were recorded and transcribed verbatim prior to a conventional content analysis that aimed to acquire direct information from new graduates without imposing preconceived categories or theoretical perspectives. New graduates reported that the RGP supported their growth as a practitioner and facilitated their learning, particularly when complemented by the experiential learning from client interactions. The RGP met their expectations with the formal education program and regular mentoring sessions highly valued. Informal support from peers and senior clinicians, while not part of the RGP, was also perceived to facilitate their growth and confidence as a physiotherapist. This study demonstrates that the provision of a structured transition program by a private practice employer was perceived by new graduates to facilitate their learning, confidence and self-efficacy. The RGP provides a useful model by which other practices may support new graduates.


Corrigendum: Impact of victory and defeat on the perceived stress and autonomic regulation of professional eSports athletes.
[This corrects the article DOI: 10.3389/fpsyg.2022.987149.].