Clinical Utility of Screening for Anxiety and Depression in Children with Tourette Syndrome.
Tourette syndrome (TS) is often co-morbid with attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Studies of TS, anxiety and depression have found variable results depending on study methodology and sample characteristics. Our aim was to examine the clinical utility of routine screening for anxiety and depression in children with TS. Using a clinic-based sample, we evaluated the proportion of children with TS meeting diagnostic criteria for ADHD, OCD, generalized anxiety disorder (GAD), separation anxiety disorder (SAD), and major depressive disorder (MDD); the frequency of above average anxiety and depressive symptoms using the Multidimensional Anxiety Scale for Children (MASC) and the Children's Depression Inventory (CDI); and the association between diagnoses and symptom severity. One hundred twenty six children were included (mean age 10.7 years). The most common comorbid disorder was ADHD (37%), followed by GAD (21%), OCD (10%), MDD (2%) and SAD (2%). On the MASC, the separation anxiety/panic subscale score was higher than all other subscale scores (p<0.0001). Clinically significant anxiety symptoms were present in 20% of the sample based on the MASC Anxiety Disorders Index, while 6% were identified as potentially clinically depressed based on the CDI Total Score. Yale Global Tic Severity Scale scores were positively correlated with total scores on the MASC (r=0.22, p=0.03) and CDI (r=0.37, p=0.0002). Routine screening children with TS for anxiety is warranted given the rate of comorbidity. Screening for depression in TS will have a higher yield in adolescents, adults, and children with more severe tics.


Bimane: A Visible Light Induced Fluorescent Photoremovable Protecting Group for the Single and Dual Release of Carboxylic and Amino Acids.
A series of ester conjugates of carboxylic and amino acids were synthesized based on bimane fluorescent photoremovable protecting group (FPRPG). The photorelease of single and dual (same as well as different) carboxylic and amino acids is demonstrated from a single bimane molecule on irradiation with visible light (λ ≥ 410 nm). The detailed mechanistic study of photorelease revealed that the release of two caged acids is simultaneous but in a stepwise pathway.


Things that go bump in the right: the effect of unimanual activity on rightward collisions.
Patients with right parietal damage and spatial neglect ignore the leftward features of their environment - causing them to bump into the left-side of doorways. In contrast, the normal population shows a mild attentional bias towards the left. Self-report measures show more collisions to the right in everyday settings. We sought to obtain a quantitative measure of lateralised bumping in a laboratory setting. Participants (n=276) walked through a narrow doorway and the experimenter recorded collisions. To investigate the association between bumping and paper-and-pencil tests of pseudoneglect, a line bisection task was administered. Unilateral activation of the hemispheres has been found to ameliorate the effects of spatial neglect. We investigated the effect of activation by asking participants to move their left-, right- or both-hands as they walked. In the both hands condition, which acted as a baseline, there were more right bumps than left bumps. The rightward bias was exasperated when the left hand moved, presumably because this movement activated the right hemisphere. In contrast, there were more left bumps when the right hand moved. The results demonstrate that bumping is not random and that we collide with the right side more often. Biases in bumping, however, were not related to biases in line bisection. The effect of hand-movement demonstrates that bumping is brought about by an imbalance of activation between the hemispheres.


A protracted outbreak of Staphylococcus epidermidis infections among patients undergoing valve replacement.
To investigate a Staphylococcus epidermidis outbreak among patients undergoing cardiac surgery. Retrospective cohort study. A 260-bed community referral center. Case-patients were patients with S. epidermidis mediastinitis, endocarditis, or both after valve implantation at Hospital de La Ribera from January to June 2002. The study population included patients undergoing valve surgery at Hospital de La Ribera from January 2000 to June 2002. From January to June 2002, 8 cases of mediastinitis, endocarditis, or both occurred among 53 patients undergoing cardiac surgery. In the same months of 2000, there had been no cases among 22 patients, and in 2001, only 1 case among 47 patients (P = .095 and P = .034, respectively). In 2002, there were 4 cases of mediastinitis and endocarditis, 3 cases of mediastinitis, and 1 case of endocarditis, all following aortic valve replacement. The epidemic curve suggested a protracted outbreak. Patients with chronic obstructive lung disease were six-fold more likely to be case-patients (95% confidence interval, 1.6-23.8). The mean duration of surgery tended to be longer in non-case-patients (161.4 +/- 57.9 minutes) than in case-patients (123.7 +/- 23.7 minutes) (P = .06). The cause of this protracted outbreak was likely multifactorial. Reemphasis of existing policies was associated with resolution of the outbreak.


Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures--a short review.
In the last 25 years data has grown exponentially dealing with the discovery of the endocannabinoid system consisting of specific cannabinoid receptors, their endogenous ligands, and enzymatic systems of their biosynthesis and degradation. Progress is being made in the development of novel agonists and antagonists with receptor subtype selectivity which should help in providing a greater understanding of the physiological role of the endocannabinoid system and perhaps also in a broad number of pathologies. This could lead to advances with important therapeutic potential of drugs modulating activity of endocannabinoid system as hypnotics, analgesics, antiemetics, antiasthmatics, antihypertensives, immunomodulatory drugs, antiphlogistics, neuroprotective agents, antiepileptics, agents influencing glaucoma, spasticity and other "movement disorders", eating disorders, alcohol withdrawal, hepatic fibrosis, bone growth, and atherosclerosis. The aim of this review is to highlight distribution of the CB1 and CB2 receptor subtypes in the nervous system and functional involvement of their specific ligands.


Clinical features, outcomes and treatment-related pneumonitis in elderly patients with esophageal carcinoma.
To investigate the clinical features and prognoses of elderly patients with esophageal carcinoma and to compare the effects of radiotherapy and rates of treatment-related pneumonitis (TRP) between elderly and non-elderly patients. A total of 236 patients with esophageal carcinoma who received radiotherapy between 2002 and 2012 were enrolled. The patients were divided into two groups: an elderly group (age ≥ 65 years) and a non-elderly group (age < 65 years). The tumor position and stage, lymph node and distant metastases, and incidence and severity of TRP were compared. Multivariate analysis was applied to identify independent prognostic factors. The median overall survival times after radiotherapy in the elderly and non-elderly groups were 18.5 and 20.5 mo, respectively. Cox regression analysis showed that TRP grade and tumor-node-metastasis (TNM) stage were independent prognostic factors in the elderly group. High-dose radiotherapy (> 60 Gy) was associated with a high incidence of TRP. Tumor TNM staging was significantly different between the two groups in which TRP occurred. Multivariate analysis showed that TNM stage was an independent prognostic factor. Esophageal carcinoma in elderly patients was relatively less malignant compared with that in non-elderly patients. An appropriate dose should be used to decrease the incidence of TRP in radiotherapy, and intensity modulated radiation therapy should be selected if possible.


Time evolution of damage under variable ranges of load transfer.
We study the time evolution of damage in a fiber bundle model in which the range of interaction of fibers varies through an adjustable stress transfer function recently introduced. We find that the lifetime of the material exhibits a crossover from mean-field to short-range behavior as in the static case. Numerical calculations showed that the value at which the transition takes place depends on the system's disorder. Finally, we have performed a microscopic analysis of the failure process. Our results confirm that the growth dynamics of the largest crack is radically different in the two limiting regimes of load transfer during the first stages of breaking.


Computer assessment and diagnostic classification of chronic pain patients.
In order to establish a diagnosis of chronic pain, emphasis is placed on a patient's report of the pain's intensity, location, and character. The aim of this study was to evaluate the feasibility of a computer assessment method to collect self-reports of pain that were then used in discriminant analyses to distinguish among chronic pain diagnoses. A convenience sample of 511 patients from two university-based pain clinics completed a computer pain assessment battery that elicited demographic information, pain drawings, pain and emotion intensity ratings, and intensity ratings of verbal descriptors. Patients classified themselves into one of six chronic pain diagnoses. Discriminant analyses were performed in an attempt to identify the unique features of patients' pain experience associated with each of the diagnostic categories. Pain drawings successfully classified patients into three of the diagnostic categories (back, head, and neck pain). In a second analysis, two pain descriptors (cramping and stabbing) separated rheumatoid arthritis patients from those with either fibromyalgia or neural pain. One descriptor of pain (cramping) and one descriptor of emotion (frustration) together distinguished between fibromyalgia and neural pain. 1) Computer assessment of a range of patient symptoms is feasible in the pain clinic. 2) Discriminant analysis based on pain drawings can distinguish among patient-reported diagnoses of back pain, headache, and neck pain. 3) Discriminant analysis based on three verbal descriptors can help to distinguish among diagnoses of fibromyalgia, neuralgia, and rheumatoid arthritis. 4) However, in general, most computerized descriptive information is not useful in distinguishing differences among pain patient diagnostic groups.


Application of mammary serum antigen assay in the management of breast cancer: a preliminary report.
A monoclonal antibody (3E1.2) based serum test using an enzyme immunoassay has been used to determine circulating levels of the breast cancer associated antigen--mammary serum antigen (MSA). Of 157 patients with early breast cancer (stage I and II) and 199 patients with advanced breast cancer (stage III and IV), 73 per cent and 87 per cent respectively had elevated MSA levels (i.e. greater than 300 inhibition units (IU). Furthermore, 40 of 44 patients (91 per cent) had a significant fall of MSA levels with reduction in tumour load by mastectomy. In addition, there was a correlation of MSA levels with the clinical course: changes in MSA levels correlated with changes in disease status (progressive disease, stable disease, disease regression) in 54 of 61 patients and antedated disease progression or recurrence by up to 8 months in some patients; and in 32 of 36 patients (89 per cent) with no clinical evidence of recurrence MSA levels did not vary by more than 25 per cent of the original MSA value over a period of 2-15 months. MSA is therefore a useful tumour marker in the diagnosis and staging of breast cancer. There is also evidence that serial estimations of MSA levels may be used to detect subclinical recurrence and the fluctuations in MSA levels might be useful in assessing response to therapy. Furthermore, it was also noted that surgical procedures such as fine needle aspiration biopsy or incisional biopsy could lead to a rise in MSA levels.


Single-lead VDD pacing system.
A single pass ventricular lead with a dual chamber electrode system, designed for VDD pacing, was implanted in 17 patients (11 men, 6 women, aged 53 to 86 years, mean 74) for symptomatic bradycardia due to second-or third-degree AV block and normal sinus node function. Bipolar atrial electrodes, diagonally displaced along the lead axis and positioned within the right atrial cavity, are used to detect atrial activity that is then differentially processed within the pacemaker. P wave amplitude (amp) derived from a PSA-DAA device at implant was 1.38 +/- 0.28 mV. P wave signal amp derived from telemetered atrial electrograms was 1.29 +/- 0.22 mV at predischarge (n = 17), 1.31 +/- 0.24 mV at 3 months (n = 15), 1.30 +/- 0.24 mV at 6 months (n = 8), 1.51 +/- 0.34 mV at 9 months (n = 4), and 1.35 +/- 0.35 mV at 12 months (n = 2); and the far-field QRS signal measured at predischarge was of negligible voltage (0.17 +/- 0.07 mV). The susceptibility of the atrial sensor system to interference was noted with chest wall stimulation and only at higher sensitivities (0.1 to 0.3 mV) and not with isometric arm exercise. Intact VDD pacing function at rest and during exercise was established using Holter and periodic ECG monitoring. Postoperative complications included one lead displacement and one pocket hematoma. Three patients died postimplant of causes unrelated to pacemaker function. Advantages of the single-lead VDD pacing include: (1) elimination of second atrial sensing lead; (2) superior atrial sensing performance; (3) effective resistance to myopotential and far-field signal interference; and (4) stability of postimplant atrial signal amplitude.


Endocannabinoids and liver disease--review.
Endocannabinoids are endogenous compounds that bind to the same receptors as tetrahydrocannabinol, the active component in marijuana and hashish. They have been found to have many physiological and patho-physiological functions, including mood alteration, control of feeding and appetite, motor and co-ordination activities, analgesia, immune modulation and gut motility. In this review we aim to elucidate current knowledge as to their role in liver physiology and disease. The major findings published to date concerning endocannabinoids and liver disease are described, and their implications with regard to understanding disease mechanisms, and the development of new treatments is considered. Recently, endocannabinoids have been implicated in the hemodynamic alterations occurring in cirrhosis. These changes appear to be mediated via specific cannabinoid receptors (CB1) on splanchnic and hepatic vascular endothelium. Plasma levels of endocannabinoids also seem to be elevated in hepatitis, and are involved in apoptosis of hepatocytes by a membrane mechanism not related to a specific receptor. Other studies suggest a beneficial role for cannabinoids in reducing the inflammation of experimental hepatitis. In an animal model of acute hepatic failure, both endocannabinoids and the antagonist to the CB1 receptor have been found to have a beneficial effect on neurological and cognitive function. Endocannabinoids appear to be involved in several aspects of acute and chronic liver disease, including vascular changes, modulation of inflammatory process and neurological function, Further research may provide new insights into the pathophysiology of liver disease, as well as a basis for novel treatment modalities.


Lifestyle behaviours of Lebanese-Australians: Cross-sectional findings from The 45 and Up Study.
Little is known regarding the health and lifestyle behaviours of Australians of Lebanese ethnicity. The available evidence suggests that Australians of Lebanese ethnicity who were born in Lebanon reportedly have higher rates of cardiovascular disease-related and type 2 diabetes-related complications when compared with the wider Australian population. The aim of this study is to compare lifestyle behaviours of middle-aged to older adults of Lebanese ethnicity born in Lebanon, Australia, and elsewhere to those of Australian ethnicity. Participants were 37,419 Australians aged ≥45 years, from the baseline dataset of The 45 and Up Study which included 4 groups of interest: those of Australian ethnicity (n = 36,707) [Reference]; those of Lebanese ethnicity born in Lebanon (n = 346); 302 those of Lebanese ethnicity born in Australia (n = 302); and those of Lebanese ethnicity born elsewhere (n = 64). Multilevel logistic regression was used to examine the odds of those of Lebanese ethnicity reporting suboptimal lifestyle behaviours (insufficient physical activity, prolonged sitting, smoking, sleep duration, and various diet-related behaviours) relative to those of Australian ethnicity. Multilevel linear regression was used to examine the clustering of suboptimal lifestyle behaviours through a 'lifestyle index' score ranging from 0-9 (sum of all lifestyle behaviours for each subject). The lifestyle index score was lower among Lebanese-born (-0.36, 95% CI -0.51, -0.22, p<0.001) and Australian-born (-0.17, 95% CI -0.32, -0.02, p = 0.031) people of Lebanese ethnicity in comparison to those of Australian ethnicity. Those of Lebanese ethnicity born in Lebanon had higher odds of reporting suboptimal lifestyle behaviours for physical activity, smoking, and sleep duration, and lower odds of reporting optimal lifestyle behaviours for sitting time, fruit, processed meat, and alcohol consumption, when compared with those of Australian ethnicity. Differences in the individual lifestyle behaviours for those of Lebanese ethnicity born in Australia and elsewhere compared with those of Australian ethnicity were fewer. Lifestyle behaviours of those of Lebanese ethnicity vary by country of birth and a lower level of suboptimal lifestyle behaviour clustering was apparent among Lebanese-born and Australian-born middle-aged to older adults of Lebanese ethnicity.


Cecal Volvulus as a Rare Complication of Osimertinib Dosed at 160 mg in Patients With EGFR-Mutant Non-small Cell Lung Cancer.
Background: Osimertinib is a 3rd-generation tyrosine kinase inhibitor (TKI) that blocks the epidermal growth factor receptor (EGFR) in non-small lung cancer (NSCLC) and has dramatically improved outcomes for patients with EGFR mutations. While gastrointestinal complications such as diarrhea have been reported with EGFR inhibitors (due to off-target interactions with EGFR receptors within the gut lining), cecal volvulus is an extremely rare complication in advanced malignancy. To date, there are no reported cases associating cecal volvulus with any EGFR TKIs. Case Presentation: In this case series, we present three cases of cecal volvulus among patients with EGFR-positive NSCLC patients treated with osimertinib dosed at double the standard 80 mg dose (160 mg daily). No patient was receiving concurrent chemotherapy or bevacizumab at the time of this described complication. In two cases where pathology was available for review, peritoneal carcinomatosis or intra-abdominal spread was not observed. In a retrospective evaluation of 101 patients treated with osimertinib in our institution, there was a statistically significant difference in the incidence of cecal volvulus among patients receiving osimertinib at 160 mg vs. patients receiving the 80 mg dose (27 vs. 0%; p < 0.001). Conclusions: To our knowledge, these are the first cases to highlight a potentially important and serious gastrointestinal complication associated with the 160 mg dose of osimertinib.


Low-dose oral combination of 17beta-estradiol and norethisterone acetate in postmenopausal women decreases factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1.
Controversies still persist concerning hormone replacement therapy (HRT) and its effects upon blood coagulation and fibrinolysis. This study was carried out to evaluate possible effects of continuously administered low-dose 17beta-estradiol (E2) and norethisterone acetate (NETA) on coagulation and fibrinolytic factors. We conducted a randomized double-blind, placebo-controlled, 1-year study in 120 healthy postmenopausal women. The three groups consisted of a placebo group (n = 40), a group receiving oral continuous combined E2 1 mg and NETA 0.25 mg (n = 40) and a group receiving oral continuous combined E2 1 mg and NETA 0.5 mg (n = 40). The two low doses of E2-NETA induced significantly lower plasma levels of factor VII, fibrinogen, antithrombin and plasminogen activator inhibitor-1 (PAI-1), compared with placebo treatmen Low-dose E2 (1 mg) in combination with NETA resulted in favorable changes of factor VII activity and fibrinogen, compared with placebo. The lower plasma levels of PAI-1 may lead to increased fibrinolytic activity. These findings suggest a decreased risk of developing coronary heart disease. Antithrombin activity was also reduced, which may increase the risk of developing venous thromboembolism. The clinical significance of the lower levels of these factors remains to be clarified.


[Maxillary sinus malformations (double wall bone) lead to chronic sinusitis in a case].
Chronic rhinosinusitis is a common otorhinolaryngological disease, although the incidence of chronic sinusitis is the result of many factors, the local anatomic abnormalities is one of the most important reasons. When maxillary sinus dysplasia that sinus cavity becomes small. These was some sinus cavity partial or complete bony septum malformation used to be reported occasionally, according to reports in the literature of this malformation rate is below 2%, bony divides sinus cavity is divided into 2 to 3 independent lacunar deformity are very rare, next we will introduce a case of sinus cavity that been divided into double deck by bone wall.


Does the General Medical Council's 2020 guidance on consent advance on its 2008 guidance?
The General Medical Council renewed its guidance on consent in 2020. In this essay, I argue that the 2020 guidance does not advance on the earlier, 2008 guidance in regard to treatments that doctors are obliged to offer to patients. In both, doctors are instructed to not provide treatments that are not in the overall benefit, or clinical interests, of the patient; although, patients are absolutely entitled to decline treatment. As such, consent has two aspects, and different standards apply to each aspect. To explore this paradigm, I propose the reconceptualisation of consent as a person's freedom to achieve treatment, using Amartya Sen's approach. Sen explains that freedom has two aspects: process and opportunity. Accordingly, a patient's freedom to achieve treatment would comprise a process for the identification of proper treatment, followed by an opportunity for the patient to accept or decline this treatment. As per Sen, the opportunity aspect is to be assessed by the standard of public reason, whereas the standard for the process aspect is variable and contingent on the task at hand. I then use this reconceptualised view of consent to analyse case law. I show that senior judges have conceived the patient's opportunity to be encompassed in information, which is to be decided by public reason. On the other hand, the process aspect relies on the private reason of medical professionals. Given the nature of professionalism, this reliance is inescapable, and it is maintained in the case law that is cited in both guidances.


The clinical features and prognostic outcomes of primary mediastinal yolk sac tumors: A retrospective analysis of 15 rare cases from multiple centers.
Primary mediastinal yolk sac tumors (PMYSTs) are a rare occurrence. As such, the clinicopathological features, treatment, and prognosis, of this disease still remain unclear. In this study, we aimed to provide further information relating to this rare malignancy in order to facilitate the creation of more specific clinical guidelines for the diagnosis and treatment of patients with PMYSTs.In this retrospective study, we recruited 15 patients who had been diagnosed with PMYST from four medical institutions to create a population-based cohort. We then used Kaplan-Meier analysis and the log-rank test to investigate and compare overall survival (OS) and progression-free survival (PFS).A total of 15 cases were identified. The mean age was 27.3 years (range: 19-34 years). The estimated 1- and 2-year PFS rates were 66.7% and 60.0%, respectively. The 1- and 2-year OS rates were both 73.3%. Computer tomography scans revealed tumors were located in the anterior middle mediastinum (5 cases), the anterior superior mediastinum (1 case), the left anterior mediastinum (3 cases), and the right anterior mediastinum (6 cases). Of the 15 patients receiving extended resections, the majority (40.0%) underwent tumor resection, partial pericardiotomy, pulmonary wedge resection, and mediastinal lymphadenectomy. R0 resections were achieved in eleven patients. Four patients underwent R2 resection and experienced postoperative complications, including pneumonia (2 cases), atelectasis (1 case), and bronchopleural fistula (1 case). Four patients developed postoperative lung metastasis. Three patients died due to progressive diseases. Disease recurred in all patients at a median of 8.0 months (range: 6.0-11.0 months).PMYST is a rare but highly malignant tumor with a poor prognosis. Tumor resection, with optimal extended surgical management, may provide patients with the best chance of a cure although postoperative complications relating to the pulmonary systems should be treated with caution.


Non-invasive Detection of Bladder Tumors Through Volatile Organic Compounds: A Pilot Study with an Electronic Nose.
Cystoscopy, the standard diagnostic for bladder tumors, is uncomfortable, invasive, and expensive. The available urine-based marker systems all lack accuracy. Measuring volatile organic compounds (VOCs) from urine is a promising alternative. This pilot study evaluates the feasibility of discriminating bladder cancer patients' urine from healthy controls with an electronic nose. Headspace measurements of urine samples of 30 patients with confirmed transitional cell carcinoma (TCC) and 30 healthy controls were performed with Cyranose 320 calculating Mahalanobis distance and linear discriminant analysis. Histology reports following TUR-BT were correlated with urine findings. After storage at -20°C, Cyranose correctly detected 28/30 already confirmed TCC samples and 26/30 healthy controls (p<0.01), sensitivity 93.3%, specificity 86.7%. Storage at -80°C led to similar results: 28/30 tumor samples and 28/30 control samples were correctly allocated; sensitivity and specificity both 93.3%. VOC detection is a promising tool to detect bladder tumors. Further research will test against possible confounders like bacteriuria.


Genetic diversity and phylogenetic relationships of seven Amorphophallus species in southwestern China revealed by chloroplast DNA sequences.
Plants species in the genus Amorphophallus are of great economic importance, as they are the only plants known to produce glucomannan. Although southwestern China has been recognized as one of the origin centres of Amorphophallus, only a few studies assessing its genetic diversity have been reported. To aid in the utilization and conservation of Amorphophallus species, we evaluated the genetic diversity and phylogenetic relationships among seven edible Amorphophallus species using three chloroplast DNA regions (rbcL, trnL and trnK-matK). The results showed that the genetic diversity at the population level was relatively low, with over half of the populations harbouring only one haplotype. The widely scattered species, A. konjac, had the largest genetic diversity, while the narrow endemic species, A. yuloensis, possessed only one haplotype. Phylogeny analysis identified three well-supported major lineages. Our study suggested that habitat fragmentation might be a driver of the genetic variation patterns within and between populations of Amorphophallus. A conservation strategy consisting of in situ conservation and germplasm collection is recommended.


Cost-Effectiveness Analysis of a Hybrid Closed-Loop System Versus Multiple Daily Injections and Capillary Glucose Testing for Adults with Type 1 Diabetes.
Background: Hybrid closed-loop systems may offer improved HbA1c levels, more time-in-range, and less hypoglycemia than alternative treatment strategies. However, it is unclear if glycemic improvements offset this technology's higher acquisition costs. Among adults with type 1 diabetes in Australia, we sought to evaluate the cost-effectiveness of a hybrid closed-loop system in comparison with the current standard of care, comprising insulin injections and capillary glucose testing. Methods: Cost-effectiveness analysis was performed using decision analysis in combination with a Markov model to simulate disease progression in a cohort of adults with type 1 diabetes and compare the downstream health and economic consequences of hybrid closed-loop therapy versus current standard of care. Transition probabilities and utilities were sourced from published studies. Costs were considered from the perspective of the Australian health care system. A lifetime horizon was considered, with annual discount rates of 5% applied to future costs and outcomes. Uncertainty was assessed with probabilistic and deterministic sensitivity analyses. Results: Use of a hybrid closed-loop system resulted in an incremental cost-effectiveness ratio of Australian dollars (AUD) 37,767 per quality-adjusted life year (QALY) gained. This is below the traditionally cited willingness to pay a threshold of $50,000 per QALY gained in the Australian setting. Sensitivity analyses that varied baseline glycemic control, treatment effects, technology costs, age, discount rates, and time horizon indicated the results to be robust. Conclusions: For adults with type 1 diabetes, hybrid closed-loop therapy is likely to be cost-effective compared with multiple daily injections and capillary glucose testing in Australia.


Evaluation of fracture resistance of endodontically treated teeth restored with composite resin along with fibre insertion in different positions in vitro.
This study was carried out to compare the different techniques of placement of polyethylene fibre (Ribbond) on reinforcement of endodontically treated teeth with MOD cavities in vitro. Forty extracted human premolars were randomly assigned to four groups (n = 10). Teeth in Groups I-IV received root canal treatment and a MOD cavity preparation, with gingival cavosurface margin 1.5 mm in coronal to cementoenamel junction. Group I served as no fibre group, Group II as occlusal fibre group, Group III as base fibre group and Group IV as dual-fibre group (occlusal and base both). Subsequent to restoring with composite resin and thermocycling, a vertical compressive force was applied at a cross-head speed of 0.5 mm min(-1) using universal testing machine until fracture. Data were analysed using one-way analysis of variance and Tukey's post hoc tests. Fracture resistance was significantly highest in dual-fibre group (P < 0.001) as compared with other groups. The highest favourable fracture rate was observed in the base fibre group (70%). This study concluded that the use of polyethylene fibre inserted over or under the restoration significantly increased the fracture strength of the root canal-treated teeth and maximum fracture resistance was observed when cavity was restored using dual-fibre technique.


Efficacy of topical galbanum oil with dry cupping in hospitalized COVID-19 patients: A randomized open-label clinical trial.
This study was designed to detect the therapeutic effects of galbanum oil plus dry cupping (a Persian medicine-based method) in hospitalized patients with coronavirus disease-2019 (COVID-19). In this randomized controlled trial, 60 hospitalized COVID-19 patients with positive polymerase chain reaction test (PCR), pulmonary involvement and blood oxygen saturation (SpO2) ≤93 mmHg, were randomly assigned into two groups to take the standard therapeutic regimen alone or alongside cupping and topical galbanum oil (Ferula gommosa oleo-gum resin) for 3-5 days. The SpO2 level, the severity of signs and symptoms of patients and laboratory parameters were compared between the two groups. Fifty-eight patients were analyzed. The SpO2 level changed from 89.27±3.82 to 90.29±3.09 mmHg (p=0.038) in control group, while it increased from 88.74±3.45 to 94.23±2.1 mmHg (<0.001) in galbanum group with a significant difference between the groups (p<0.001). Fever, cough, dyspnea, and anorexia alleviated in the galbanum group more than the control (p=0.003, 0.001, 0.01, and 0.04, respectively). No adverse effects were reported due to galbanum oil and cupping therapy. Dry cupping with galbanum oil alongside the routine therapeutic regimen could be more effective than the routine therapeutic regimen alone for improving SpO2 level and alleviating fever, cough, and dyspnea in COVID-19 patients.


[Mortality of interventricular septum rupture after acute myocardial infarction with surgical management].
ventricular septal rupture is a rare complication of myocardial infarction. It is considered the most serious mechanical disturbance in these cases. The mortality of patients during the hospital period receiving surgical treatment for this complication is described. a case series study, including patients with ventricular septal rupture posterior to myocardial infarction, detected with a retrospective review of records of patients subjected to surgical repair from December 2005 to December 2010. a total of 20 patients were included, with an average age of 56 years (48-65 years), male gender in 16 cases (80%), and a male: female relation of 4:1. Ten (50%) of the patients died; five due to multiple organ failure, one from nosocomial pneumonia, two from ventricular fibrillation, and two from refractory shock secondary to biventricular failure during the surgery. The factors identified for poor prognosis were the average time of 145 minutes on cardiopulmonary bypass, and acute kidney injury in six cases, requiring replacement therapy. ventricular septal rupture is a rare complication with a high mortality. Without surgical treatment mortality can reach almost 100%. The mortality of this pathology treated with surgical closing in our hospital was 50%, similar to other published reports. Our findings confirm that although surgery for ventricular septal rupture has a high mortality it should be carried out because it is a surgical emergency.


Epigenetic Regulation of BDNF Gene during Development and Diseases.
Brain-derived neurotrophic factor (BDNF) is required for the development of the nervous system, proper cognitive function and memory formation. While aberrant expression of BDNF has been implicated in neurological disorders, the transcriptional regulation of BDNF remains to be elucidated. In response to different stimuli, BDNF expression can be initiated from different promoters. Several studies have suggested that the expression of BDNF is regulated by promoter methylation. An emerging theme points to the possibility that histone modifications at the BDNF promoters may link to the neurological pathology. Thus, understanding the epigenetic regulation at the BDNF promoters will shed light on future therapies for neurological disorders. The present review summarizes the current knowledge of histone modifications of the BDNF gene in neuronal diseases, as well as the developmental regulation of the BDNF gene based on data from the Encyclopedia of DNA Elements (ENCODE).


Critical congenital heart disease.
We have reviewed the outcome in 94 infants who underwent diagnostic cardiac catheterization in the 1st month of life during the period 1976-1980. Eighty-three were shown to have congenital heart disease, and in nearly 50% further active intervention was attempted. Mortality directly related to catheterization was only 1%, although hospital mortality after surgery was 44%, and overall mortality was 53%. The prevalence of cardiac abnormalities encountered has remained unchanged over the past 10 years, but there has been a gradual improvement in prognosis. Factors contributing to this are discussed.


Chronic K depletion stimulates rat renal brush-border membrane Na-citrate cotransporter.
Chronic K depletion (KD) causes hypocitraturia. In the present studies, the effect of KD, induced by a low-K diet for 14 days (serum [K] 4.1 +- 0.1, control vs. 2.2 +/- 0.1 meq/l, KD, P less than 0.01), on renal cortical brush-border membrane (BBM) Na-citrate cotransporter activity was examined. KD significantly decreased fractional citrate excretion (3.90 +/- 0.68 vs. 0.53 +/- 0.10%, P less than 0.01). This was paralleled by a significant increase in the initial linear rate of BBM Na-dependent citrate transport (81 +/- 4 vs. 141 +/- 6 pmol citrate.5 s-1.mg protein-1, P less than 0.01). Kinetic studies varying extravesicular citrate concentration demonstrated that KD increased the maximal activity (Vmax) (152 +/- 17 vs. 296 +/- 14 pmol citrate.5 s-1.mg protein-1, P less than 0.01) with no difference in citrate affinity (118 +/- 23, control vs. 135 +/- 22 microM citrate, KD). Similarly, when extravesicular Na concentration was varied, KD increased the Vmax (132 +/- 9 vs. 206 +/- 6 pmol citrate.5 s-1.mg protein-1, P less than 0.01) with no difference in Na affinity (29 +/- 3, control vs. 28 +/- 1 mM Na, KD). The effect of KD on Na-citrate cotransport was specific in that KD did not alter Na-glucose (84 +/- 12, control vs. 89 +/- 5 pmol glucose.5 s-1.mg protein-1, KD) or Na-proline (87 +/- 3, control vs. 84 +/- 5 pmol proline.5 s-1.mg protein-1, KD) cotransport. In conclusion, KD increases the Vmax of the proximal tubule apical membrane Na-citrate cotransporter.(ABSTRACT TRUNCATED AT 250 WORDS)


Targeting the Hepatocyte Growth Factor and c-Met Signaling Axis in Bone Metastases.
Bone metastasis is the terminal stage disease of prostate, breast, renal, and lung cancers, and currently no therapeutic approach effectively cures or prevents its progression to bone metastasis. One of the hurdles to the development of new drugs for bone metastasis is the complexity and heterogeneity of the cellular components in the metastatic bone microenvironment. For example, bone cells, including osteoblasts, osteoclasts, and osteocytes, and the bone marrow cells of diverse hematopoietic lineages interact with each other via numerous cytokines and receptors. c-Met tyrosine kinase receptor and its sole ligand hepatocyte growth factor (HGF) are enriched in the bone microenvironment, and their expression correlates with the progression of bone metastasis. However, no drugs or antibodies targeting the c-Met/HGF signaling axis are currently available in bone metastatic patients. This significant discrepancy should be overcome by further investigation of the roles and regulation of c-Met and HGF in the metastatic bone microenvironment. This review paper summarizes the key findings of c-Met and HGF in the development of novel therapeutic approaches for bone metastasis.


Simultaneous assessment of blood flow in UVB-inflamed human skin by laser Doppler flowmetry and the 133-xenon washout technique.
The purpose of the study was to compare skin blood flow by laser Doppler flowmetry (LDF) and the 133-Xenon washout technique in UVB-inflamed human skin. Six healthy subjects participated in the study. Forearm skin blood flow was measured prior to irradiation and then 8, 24, 48 and 72 h after the exposure to twice the minimal erythema dose of UVB. Baseline blood flow as measured by the 133-Xenon washout method was 5.2 (range 3.0 to 10.4) ml/100g/min and LDF flux was 3.1 (range 2.7 to 5.7) arbitrary units. Following irradiation, maximum blood flow increase as evaluated by the 133-Xenon washout was 10.8 (95% confidence interval 3.7 to 11.3) times baseline blood flow, corresponding to an absolute blood flow of 47.5 (range 33.8 to 56.3) ml/100g/min. Maximum increase after induction of inflammation as assessed by LDF was 34.6 (95% confidence interval 24.6 to 56.5) times baseline flux. The two methods showed comparable time courses in all subjects. A significant correlation between the two methods was found, Spearman's rho = 0.54, p = 0.006. The relative LDF blood flow increase was 4.2-fold (95% confidence interval 2.7 to 5.0) greater than the increase measured by the 133-Xenon washout method. These results are at variance with previous comparative studies of the two methods. Some explanations are discussed.


[Optic nerve head parameters as measured by confocal scanning laser (Heidelberg Retina Tomograph II) in normal, ocular hypertensive and glaucomatous subjects].
To compare the optic nerve parameters measured by confocal scanning laser in normal, ocular hypertensive and glaucomatous eyes; and in groups of ocular hypertensive eyes, classification of these according to the optic nerve appearance and to short-wavelength automated perimetry (SWAP) results. 101 eyes of 101 normal subjects, 247 eyes of 247 ocular hypertensive subjects and 102 eyes of 102 glaucomatous subjects were studied. Subjects were classified based on intraocular pressure and standard automated perimetry (AP) performance. Hypertensive subjects were classified into ocular hypertensive and preperimetric glaucoma, and into ocular hypertensive with normal SWAP and hypertensive with pathological SWAP findings. Every patient underwent evaluation of the optic nerve, AP, SWAP and confocal scanning laser ophthalmoscopy (HRT II), resulting in the acquisition of topographic parameters of the optic nerve, which were then compared between the different groups. Significant differences (p<0.05) were found between normal subjects and glaucomatous eyes in all optic nerve parameters except disc area (2.23/2.1), height variation contour (0.41/0.39) and average variability (0.05/0.04). Ocular hypertensive eyes showed an overlap when compared with normal and glaucoma groups. No differences were found between normal subjects and those with ocular hypertension in mean retinal nerve fiber layer thickness (0.24/0.24) or between those with ocular hypertension and glaucoma in mean cup depth (0.28/0.3). Nevertheless, when those with ocular hypertension were segregated based on clinical evaluation of optic nerve or SWAP performance, the ability to define the presence of structural glaucoma damage improved significantly. HRT enables moderate discrimination between normal, ocular hypertensive and glaucoma subjects. The use of diagnostic tests to detect early glaucomatous damage (such as short-wavelength automated perimetry) in ocular hypertensive eyes improves the ability of HRT to discriminate glaucoma.


Cornea recipients: are their opinions and attitudes toward organ donation different from those of the general population?
Cornea transplantation provides a second chance for people with poor visual function. Unfortunately, there is a major shortage of donor cornea tissue. The purpose of this study was to evaluate the attitudes and willingness to donate organs among cornea transplant recipients. Sixty-eight patients who underwent cornea transplantation between January 2002 and May 2003 were asked to complete a questionnaire dealing with their attitudes toward cornea and organ donation, and willingness to donate an organ. Religion was a contributing factor for a negative decision to donate organs. Only 29% of participants, most of whom were nonreligious were carrying a signed donation card. Fifty-eight percent of the patients knew that the cornea graft is derived from a deceased person; most of these patients were of European or American origin. Seventy-three percent knew that donation requires the agreement of a family member. Age, gender, marital status, and education were not significantly associated with attitude toward donation. Stronger efforts are needed by transplant coordinators, physicians, and nurses to improve the education and knowledge of patients and their families about the basic aspects of transplantation. Greater public awareness may increase the willingness to donate organs.


Cross-reactivity with SIVmac in east African HIV-1-positive sera: evidence against double infection with HIV-1 and a SIVmac/HIV-2-like virus.
IgG antibodies reactive with simian immunodeficiency virus isolated from a rhesus monkey suffering from simian acquired immunodeficiency syndrome (SIVmac, strain 239, a virus which is very closely related to human immunodeficiency virus type 2-HIV-2) were found in 18 of 120 Swedish and 8 of 11 east African confirmed HIV-1 antibody positive (HIV-1 ab+) sera, both by enzyme immunoassay and electrophoretic immunoblotting (p = 1 x 10(-6). In electrophoretic immunoblotting most of the cross-reactivity of SIVmac-reactive sera occurred on p27, the major gag protein of SIVmac. The possibility that SIVmac antibody reactivity could be due to double infection with HIV-1 and a SIVmac-related virus was eliminated by the results of absorptions between sera of Swedish and west and east African origin and viral antigens (SIVmac and North American or African/Haitian strains of HIV-1) coupled to agarose beads. HIV-2 ab+ and SIVmac reactive west African sera recognized SIVmac epitopes unrelated to HIV-1, whereas HIV-1 ab+, SIVmac reactive east African, and Swedish sera recognized SIVmac epitopes cross-reactive with epitopes present in both African and North American HIV-1 strains. No unique SIVmac-reactive African HIV-1 epitopes could thus be defined. Neither did absorption of Swedish and African HIV-1-positive sera with different HIV-1 strains (1 Haitian, 2 Zairian, and 1 North American) give evidence for unique epitopes.


[Smoking and preoperative fasting--are there evidence-based guidelines?].
Over the last years several clinical studies have modified the guidelines for preoperative fasting to reduce the risk of pulmonary aspiration. In most western countries the following guidelines are accepted: for clear liquids 2 hours, breast feeding 4 hours, small meals and breast milk substitutes 6 hours, heavy meals 8 hours. Since preoperative smoking is acknowledged as a risk factor, it should be ceased in most clinics 6 hours before induction of anaesthesia, as well. Smoking, however, does not increase the risk of pulmonary aspiration, as is often maintained, but increases the risk of postoperative pulmonary complications. To reduce the risk of perioperative pulmonary complications, cessation of smoking is necessary 8 weeks before operation. Stopping smoking only a few days before operation and anaesthesia even tends to increase the risk of pulmonary complications. Regarding cardiac complications, cessation of smoking 12 hours before anaesthesia is sufficient to reduce the incidence of cardiac ischaemia.


Magnetic resonance imaging (MRI)-defined cartilage degeneration and joint pain are associated with poor physical function in knee osteoarthritis - the Oulu Knee Osteoarthritis study.
The main aim was to investigate the associations between Magnetic Resonance Imaging (MRI)-defined structural pathologies of the knee and physical function. A cohort study with frequency matching on age and sex with eighty symptomatic subjects with knee pain and suspicion or diagnosis of knee osteoarthritis (OA) and 57 asymptomatic subjects was conducted. The subjects underwent knee MRI, and the severity of structural changes was graded by MRI Osteoarthritis Knee Score (MOAKS) in separate knee locations. WOMAC function subscores were recorded and physical function tests (20-m and 5-min walk, stair ascending and descending, timed up & go and repeated sit-to-stand tests) performed. The association between MRI-defined structural pathologies and physical function tests and WOMAC function subscores were evaluated by linear regression analysis with adjustment for demographic factors, other MRI-features and pain with using effect size (ES) as a measure of the magnitude of an association. Cartilage degeneration showed significant association with poor physical performance in TUG-, stair ascending and descending-, 20-m- and 5-min walk-tests (ESs in the subjects with cartilage degeneration anywhere between 0.134 [95%CI 0.037-0.238] and 0.224 [0.013-0.335]) and with increased WOMAC function subscore (ES in the subjects with cartilage degeneration anywhere 0.088 [0.012-0.103]). Also, lateral meniscus maceration and extrusion were associated with poor performance in stair ascending test (ESs 0.067 [0.008-0.163] and 0.077 [0.012-0.177]). After adjustments cartilage degeneration was associated with both decreased self-reported physical function and poor performance in the physical function tests. Furthermore, subjects with lateral meniscus maceration and extrusions showed significantly worse performance in stair ascending tests.


Fluorescent Measurement of Synaptic Activity Using FM Dyes in Dissociated Hippocampal Cultured Neurons.
Release and recycling of synaptic vesicles are essential for neurotransmission and synaptic plasticity. To gain mechanistic understanding of these processes, direct measurements of vesicle release and retrieval is indispensable. Styryl dyes like FM1-43 and FM4-64 have been widely used for this purpose and their loading and unloading are reliable measurements for synaptic vesicle release and retrieval in cultured neurons. This protocol describes in detail the procedure of using styryl dyes to label and measure synaptic vesicle uptake and release in cultured rat hippocampal neurons. We also include a brief description of hippocampal culture. In the end, we briefly discuss the commonality and difference among FM dye, pH-sensitive fluorescent proteins and quantum dots in terms of measuring synaptic vesicle behavior.


Diagnosis of coronary in-stent restenosis with multidetector row spiral computed tomography.
The purpose of this study was to assess the accuracy of a new generation spiral multidetector computed tomography (MDCT) scanner (Brilliance 40, Philips Medical Systems, Cleveland, Ohio) in the diagnosis of coronary in-stent restenosis (ISR). Noninvasive imaging of ISR would be clinically useful, but artifacts caused by metallic stent struts have limited the role of early generation MDCT scanners. We examined 65 patients (age 63 +/- 12 years, 48 [73.8%] men) with 111 implanted coronary stents who were referred for repeat invasive coronary angiography (ICA). Patients underwent 40-slice MDCT one to three days before scheduled ICA, using intravenous contrast enhancement. Images were reconstructed in multiple formats using retrospective electrocardiographic gating. Stents were viewed in their long and short axes and luminal contrast attenuation graded from MDCT grade 1 (minimal restenosis) to 4 (severe restenosis) by consensus of two observers. In-stent restenosis (>/=60% luminal narrowing by quantitative coronary angiography) was found on ICA in 18 (16.2%) of the stented segments and in 16 (24.6%) patients. The MDCT findings correlated with ICA restenosis, with restenosis in only 1 of 59 (1.6%) MDCT grade 1 segments, but in more than three-quarters (12 of 15, 80%) of MDCT grade 4 segments (sensitivity 72.2%, specificity 92.5%, positive predictive value [PPV] 65.0%, negative predictive value [NPV] 94.5% [five stents not assessable by MDCT considered as restenosis]). Using MDCT grades 3 or 4 combined for restenosis, sensitivity of MDCT was 88.9%, specificity 80.6%, PPV 47.1%, and NPV 97.4%. In-stent restenosis can be diagnosed with moderate sensitivity using a new generation 40-slice MDCT scanner. The high NPV implies a significant role for MDCT in excluding ISR.


Effect of Chemical and Physical Properties on the In Vitro Degradation of 3D Printed High Resolution Poly(propylene fumarate) Scaffolds.
Two distinct molecular masses of poly(propylene fumarate) (PPF) are combined with an additive manufacturing process to fabricate highly complex scaffolds possessing controlled chemical properties and porous architecture. Scaffolds were manufactured with two polymer molecular masses and two architecture styles. Degradation was assessed in an accelerated in vitro environment. The purpose of the degradation study is not to model or mimic in vivo degradation, but to efficiently compare the effect of modulating scaffold properties. This is the first study addressing degradation of chain-growth synthesized PPF, a process that allows for considerably more control over molecular mass distribution. It demonstrates that, with greater process control, not only is scaffold fabrication reproducible, but the mechanical properties and degradation kinetics can be tailored by altering the physical properties of the scaffold. This is a clear step forward in using PPF to address unmet medical needs while meeting regulatory demands and ultimately obtaining clinical relevancy.


Improved adhesive properties of recombinant bifidobacteria expressing the Bifidobacterium bifidum-specific lipoprotein BopA.
Bifidobacteria belong to one of the predominant bacterial groups in the intestinal microbiota of infants and adults. Several beneficial effects on the health status of their human hosts have been demonstrated making bifidobacteria interesting candidates for probiotic applications. Adhesion of probiotics to the intestinal epithelium is discussed as a prerequisite for colonisation of and persistence in the gastrointestinal tract. In the present study, 15 different strains of bifidobacteria were tested for adhesion. B. bifidum was identified as the species showing highest adhesion to all tested intestinal epithelial cell (IEC) lines. Adhesion of B. bifidum S17 to IECs was strongly reduced after treatment of bacteria with pronase. These results strongly indicate that a proteinaceous cell surface component mediates adhesion of B. bifidum S17 to IECs. In silico analysis of the currently accessible Bifidobacterium genomes identified bopA encoding a lipoprotein as a B. bifidum-specific gene previously shown to function as an adhesin of B. bifidum MIMBb75. The in silico results were confirmed by Southern Blot analysis. Furthermore, Northern Blot analysis demonstrated that bopA is expressed in all B. bifidum strains tested under conditions used to cultivate bacteria for adhesion assays. The BopA gene was successfully expressed in E. coli and purified by Ni-NTA affinity chromatography as a C-terminal His6-fusion. Purified BopA had an inhibitory effect on adhesion of B. bifidum S17 to IECs. Moreover, bopA was successfully expressed in B. bifidum S17 and B. longum/infantis E18. Strains overexpressing bopA showed enhanced adhesion to IECs, clearly demonstrating a role of BopA in adhesion of B. bifidum strains. BopA was identified as a B. bifidum-specific protein involved in adhesion to IECs. Bifidobacterium strains expressing bopA show enhanced adhesion. Our results represent the first report on recombinant bifidobacteria with improved adhesive properties.


Single cell profiling of surface carbohydrates on Bacillus cereus.
Cell surface carbohydrates are important to various bacterial activities and functions. It is well known that different types of Bacillus display heterogeneity of surface carbohydrate compositions, but detection of their presence, quantitation and estimation of variation at the single cell level have not been previously solved. Here, using atomic force microscopy (AFM)-based recognition force mapping coupled with lectin probes, the specific carbohydrate distributions of N-acetylglucosamine and mannose/glucose were detected, mapped and quantified on single B. cereus surfaces at the nanoscale across the entire cell. Further, the changes of the surface carbohydrate compositions from the vegetative cell to spore were shown. These results demonstrate AFM-based 'recognition force mapping' as a versatile platform to quantitatively detect and spatially map key bacterial surface biomarkers (such as carbohydrate compositions), and monitor in situ changes in surface biochemical properties during intracellular activities at the single cell level.


Algorithm to determine cost savings of targeting antimicrobial therapy based on results of rapid diagnostic testing.
A rapid diagnosis of pneumococcal pneumonia may allow the earlier use of narrow-spectrum antimicrobial therapy. It is unknown, however, whether rapid diagnostic testing of patients hospitalized with community-acquired pneumonia (CAP) admitted to hospital lowers costs. Therefore, an algorithm to calculate the costs associated with the diagnosis and treatment of CAP was formulated. Subsequently, the algorithm was applied to clinical data for 122 consecutively admitted patients with CAP whose sputum samples were Gram stained and whose urine was tested for Streptococcus pneumoniae antigen. The costs of initial antimicrobial therapy, personnel, and materials were measured. Compared to the most expensive empirical regimen, rapid diagnostic testing would result in cost savings per patient (PP) of 3.51 Euros for Gram staining and 8.11 Euros for urinary pneumococcal antigen testing (1 Euro is equal to 1.13 US dollars, from 2000 to 2002). Compared to the cheapest regimen, Gram staining would increase the cost by 2.25 Euros PP, and urinary antigen testing would increase the cost by 24.26 Euros PP. In our setting, the use of rapid diagnostic testing would not lower costs. Cost savings depend, however, on the differences in the prices of the different antibiotics chosen and the proportion of evaluable and positive samples.


Tumor necrosis factor alpha activation of the apoptotic cascade in murine articular chondrocytes is associated with the induction of metalloproteinases and specific pro-resorptive factors.
Tumor necrosis factor alpha (TNFalpha) blockade provides substantive reduction of the symptoms of rheumatoid arthritis (RA). While the biologic actions of TNFalpha have been well characterized in immune and synovial cells, which are known to be major contributors to the progression of cartilage destruction in RA, the current studies were designed to assess the direct effects of TNFalpha on chondrocytes. We examined the expression of several groupings of messenger RNA (mRNA) that define key biologic pathways that have previously been associated with either the general actions of TNFalpha or cartilage destruction, in murine articular chondrocytes isolated from wild-type mice and TNFalpha receptor-null (p55/p75(-/-)) mice. TNFalpha induced the expression of multiple mRNA that facilitate apoptosis and lead to apoptosis-induced cell death. The induction of apoptosis was accompanied by the increased expression of several factors involved in the regulation of skeletal tissue proteolysis and resorption. Quantitative increases from 2-fold to >10-fold were seen for inducible nitric oxide synthase, matrix metalloproteinase 3, macrophage colony-stimulating factor, and osteoprotegerin mRNA expression. The dependence of the induction of these mRNA on TNFalpha was confirmed by comparison with the effects of TNFalpha on chondrocytes isolated from receptor-null mice. These findings demonstrate that TNFalpha alters the expression of a complex array of genes within murine chondrocytes that contribute to the destruction of joint surfaces, independent of its actions on synovial and immune cells. Further studies are needed to clarify the biologic actions of TNFalpha in human cartilage cells.


Enzyme-linked immunosorbent assay for the ganglioside GM2-activator protein. Screening of normal human tissues and body fluids, of tissues of GM2 gangliosidosis, and for its subcellular localization.
An enzyme-linked immunosorbent assay was developed for the quantitation of the human activator protein for ganglioside GM2 degradation by beta-N-acetyl-D-hexosaminidase A. With this assay, various tissues and body fluids of normal subjects and of patients with variant forms of GM2 gangliosidosis were screened for their GM2-activator content. The highest content of this protein was found in kidney. Tissues from patients with variant AB of infantile GM2 gangliosidosis contained only low levels (up to 5% of that of normal controls) of cross-reacting material. On subcellular fractionation of normal human skin fibroblasts, the activator was found to co-distribute with the lysosomal marker enzyme beta-hexosaminidase.


The risks of low hemoglobin deferral in a large retrospective cohort of plasmapheresis donors and the influence factors of return for a subsequent donation in China.
According to the Technical Operation Procedures for Plasmapheresis Collection Station (2019) in China, plasmapheresis donors with low hemoglobin (Hb) levels (men <12.0 g/dL; women <11.0 g/dL) were deferred for at least 2 weeks. The purpose of this retrospective study was to survey the demographic characteristics of plasmapheresis donors with low Hb deferral (LHD) and identify at-risk LHD donors, so as to enhance donor safety and improve donation service management. From 2018 to 2020, a multi-center study involving plasmapheresis donors from 18 plasmapheresis centers in three provinces (Sichuan, Yunnan and Hunan) of China was conducted. Donor demographics (age, sex) and donation information (date of donation, first-time donors vs. repeat donors, the number of lifetime donations, the number of donations in the last 12 months, and whether the LHD donor returned for a subsequent donation) were collected. The Cochran-Mantel-Haenszel method was used to explore the risk factors for LHD while adjusting for the different provinces. Logistic regression analysis was used to investigate the factors influencing the return for a subsequent donation after LHD. A total of 497,039 plasmapheresis donors were included. Female donors' LHD rate was 0.15% on average, while male donors' LHD rate was 0.01%. Female donors aged 41-50 years old (OR: 2.276, 95% CI [1.333-3.887], p = 0.002) were more likely to experience LHD temporarily than those aged 18-30 years old. For female donors, compared with donations in the winter, they had a higher risk for LHD in the summer (OR: 2.217, 95% CI [1.670-2.943], p < 0.001), spring (OR: 2.402, 95% CI [1.806-3.196], p < 0.001), and fall (OR: 2.002, 95% CI [1.500-2.673], p < 0.001). Among the LHD donors, those who had donated more frequently in the past were more likely to return for a subsequent donation (p = 0.012). Female donors were at a higher risk of LHD, particularly between the ages of 41 and 50. A clear seasonal pattern in the rate of LHD was observed. In the winter, the risk of LHD was the lowest; thus, it was advised to recruit plasmapheresis donors throughout the winter and to make the required adjustments for recruitment measures during other seasons. The number of previous donations was correlated with the return rate after LHD. Our observations could have practical implications for plasmapheresis donor management.


Teleanalytic Therapy in the Era of Covid-19: Dissociation in the Countertransference.
While we and our patients have many transferences to the modality of video or telephone therapy, these meanings are ultimately not intrinsic to the medium itself. Rather, they are symbolic meanings we make of the modality. This paper discusses the symbolic meanings that we attribute to teletherapy and the ways we may use these attributed meanings to dissociate the trauma of Covid-19. It also explores the clinical opportunities in identifying these dissociated countertransferential experiences and embodying them in our own and our patients' experiences.


Villars nodule: An incidental finding with uterine fibroids and infertility-A case report.
Villar's nodule is a rare presentation of endometriosis. Only a few cases report coexistence with uterine fibroids and infertility. We report an incidental discovery of a bleeding umbilical lesion confirmed as Villar's nodule in a 37-year-old woman with primary infertility who presented for myomectomy on account of leiomyomas.


I am the metre: The representation of one's body size affects the perception of tactile distances on the body.
Humans must ground the perception of one's body in a mental representation to move in space and interact with objects. This representation can be temporarily altered artificially. In the full-body illusion (FBI), participants see a virtual (or filmed) body receiving a tactile stimulation. When participants receive touches on their body similarly to the seen one (i.e., homologous location and synchronous timing), they embody the seen alien body. While the subjective embodiment of alien bodies of different sizes has been already manipulated with the FBI, it remains unexplored whether the body-metric perception is impacted too. We first developed a new setup for the FBI using 360° videos to favour the embodiment. The FBI was induced for bodies of three sizes adopting anatomical and non-anatomical viewpoints, and we measured the subjective embodiment. The results suggest that humans can embody normal size or bigger bodies seen from anatomical viewpoints, but not smaller ones. We then investigated if the FBI modulates the body-metric representation. We found that the resized bodies' vision affects the perception of one's body-metric representation, but this was independent of the embodiment, suggesting that the FBI alters the body representation at different levels with a specific impact.


Outcomes of Bariatric Surgery in Morbidly Obese Patients with Multiple Sclerosis.
Obesity is common in patients with multiple sclerosis (MS); however, safety and efficacy of bariatric surgery in this population remain unclear. A database of 2,918 was retrospectively reviewed, yielding 22 (0.75%) severely obese patients with MS who underwent bariatric surgery. Sixteen surgical patients with complete follow-up data were matched to a nonsurgical control group of MS patients, based on age, BMI, MS subtype, and length of follow-up. MS relapse rates and trends in the timed twenty-five foot walk test (T25FW) were compared. In the surgical group (gastric bypass n = 19, sleeve gastrectomy n = 3), preoperative BMI was 46.5 ± 7.2 Kg/m2 and average excess weight was 60.4 kg. Follow-up data was collected at 59.0 ± 29.8 months. There were two major and four minor complications. Five patients required readmission and there were no mortalities. Percent excess weight loss was 75.5 ± 27.0%. In the 16 patients with follow-up data, patients who underwent bariatric surgery were significantly faster on the T25FW compared to the nonsurgical population. In conclusion, bariatric surgery is relatively safe and effective in achieving weight loss in patients with MS. In addition, surgery may help patients maintain ambulation. Findings support the need for further studies on bariatric surgery and disease-specific outcomes in this population.


Learning predictive cognitive maps with spiking neurons during behavior and replays.
The hippocampus has been proposed to encode environments using a representation that contains predictive information about likely future states, called the successor representation. However, it is not clear how such a representation could be learned in the hippocampal circuit. Here, we propose a plasticity rule that can learn this predictive map of the environment using a spiking neural network. We connect this biologically plausible plasticity rule to reinforcement learning, mathematically and numerically showing that it implements the TD-lambda algorithm. By spanning these different levels, we show how our framework naturally encompasses behavioral activity and replays, smoothly moving from rate to temporal coding, and allows learning over behavioral timescales with a plasticity rule acting on a timescale of milliseconds. We discuss how biological parameters such as dwelling times at states, neuronal firing rates and neuromodulation relate to the delay discounting parameter of the TD algorithm, and how they influence the learned representation. We also find that, in agreement with psychological studies and contrary to reinforcement learning theory, the discount factor decreases hyperbolically with time. Finally, our framework suggests a role for replays, in both aiding learning in novel environments and finding shortcut trajectories that were not experienced during behavior, in agreement with experimental data.


Factors hindering the implementation of surgical site infection control guidelines in the operating rooms of low-income countries: a mixed-method study.
The study aims to find the factors hindering the implementation of surgical site infection control guidelines in the operating rooms of low-income countries. The design of the study is a mixed-method sequential explanatory study. The setting is Shifa International Hospital and Pakistan Institute of Medical Sciences, Islamabad, Pakistan. Participants are health care workers. A questionnaire and structured key informant interviews probed the perspectives and perceptions of different stakeholders regarding the factors which hinder the implementation of surgical site infection control guidelines. Two-hundred fifty-two health care workers took part in the survey. The response rate was 90%. The majority of the participants was based in private teaching hospitals (63.9%) and 36.1% in the public sector teaching hospitals. The factors of surveillance, knowledge, education, and culture had low scores. Qualitative data analysis revealed the hindering factors in the implementation of surgical site infection control guidelines in the operating rooms of low-income country. The important one are lack of a surveillance system, education, and culture of infection control. This study identified hindering factors regarding implementation of surgical site infection control guidelines in the operating rooms at the institutional and individual level involved in patient care. The identification of these hindering factors may help politicians, policy makers, and institutions to identify the strategies for overcoming these hindering factors. Education is the key factor for success. By offering training to health care workers, we significantly contribute to decrease the incidence of SSIs in the low-income country.


Generalized grazing-incidence-angle X-ray diffraction (G-GIXD) using image plates.
A new and more 'generalized' grazing-incidence-angle X-ray diffraction (G-GIXD) method which enables simultaneous measurements both of in- and out-of-plane diffraction images from surface and interface structures has been developed. While the method uses grazing-incidence-angle X-rays like synchrotron radiation as an incident beam in the same manner as in 'traditional' GIXD, two-dimensional (area) detectors like image plates and a spherical-type goniometer are used as the data-collection system. In this way, diffraction images both in the Seemann-Bohlin (out-of-plane) and GIXD geometry (in-plane) can be measured simultaneously without scanning the detectors. The method can be applied not only to the analysis of the in-plane crystal structure of epitaxically grown thin films, but also to more general research topics like the structural analysis of polycrystalline mixed phases of thin surface and interface layers.


Human activities modulate reciprocal effects of a subterranean ecological engineer rodent, Tachyoryctes macrocephalus, on Afroalpine vegetation cover.
Human activities, directly and indirectly, impact ecological engineering activities of subterranean rodents. As engineering activities of burrowing rodents are affected by, and reciprocally affect vegetation cover via feeding, burrowing and mound building, human influence such as settlements and livestock grazing, could have cascading effects on biodiversity and ecosystem processes such as bioturbation. However, there is limited understanding of the relationship between human activities and burrowing rodents. The aim of this study was therefore to understand how human activities influence the ecological engineering activity of the giant root-rat (Tachyoryctes macrocephalus), a subterranean rodent species endemic to the Afroalpine ecosystem of the Bale Mountains of Ethiopia. We collected data on human impact, burrowing activity and vegetation during February and March of 2021. Using path analysis, we tested (1) direct effects of human settlement on the patterns of livestock grazing intensity, (2) direct and indirect impacts of humans and livestock grazing intensity on the root-rat burrow density and (3) whether human settlement and livestock grazing influence the effects of giant root-rat burrow density on vegetation and vice versa. We found lower levels of livestock grazing intensity further from human settlement than in its proximity. We also found a significantly increased giant root-rat burrow density with increasing livestock grazing intensity. Seasonal settlement and livestock grazing intensity had an indirect negative and positive effect on giant root-rat burrow density, respectively, both via vegetation cover. Analysing the reciprocal effects of giant root-rat on vegetation, we found a significantly decreased vegetation cover with increasing density of giant root-rat burrows, and indirectly with increasing livestock grazing intensity via giant root-rat burrow density. Our results demonstrate that giant root-rats play a synanthropic engineering role that affects vegetation structure and ecosystem processes.


The defect detection for X-ray images based on a new lightweight semantic segmentation network.
The tire factory mainly inspects tire quality through X-ray images. In this paper, an end-to-end lightweight semantic segmentation network is proposed to realize the error detection of bead toe. In the network, firstly, the texture feature of different regions of tire is extracted by an encoder. Then, we introduce a decoder to fuse the output feature of the encoder. As the dimension of the feature maps is reduced, the positions of bead toe in the X-ray image have been recorded. When evaluating the final segmentation effect, we propose a local mIoU(L-mIoU) index. The segmentation accuracy and reasoning speed of the network are verified on the tire X-ray image set. Specifically, for 512 × 512 input images, we achieve 97.1% mIoU and 92.4% L-mIoU. Alternatively, the bead toe coordinates are calculated using only 1.0 s.


A randomised controlled trial of methadone maintenance treatment versus wait list control in an Australian prison system.
The aim was to determine whether methadone maintenance treatment reduced heroin use, syringe sharing and HIV or hepatitis C incidence among prisoners. All eligible prisoners seeking drug treatment were randomised to methadone or a waitlist control group from 1997 to 1998 and followed up after 4 months. Heroin use was measured by hair analysis and self report; drugs used and injected and syringe sharing were measured by self report. Hepatitis C and HIV incidence was measured by serology. Of 593 eligible prisoners, 382 (64%) were randomised to MMT (n=191) or control (n=191). 129 treated and 124 control subjects were followed up at 5 months. Heroin use was significantly lower among treated than control subjects at follow up. Treated subjects reported lower levels of drug injection and syringe sharing at follow up. There was no difference in HIV or hepatitis C incidence. Consideration should be given to the introduction of prison methadone programs particular where community based programs exist.


Counting repetitions: an observational study of video game play in people with chronic poststroke hemiparesis.
The use of video gaming as a therapeutic intervention has increased in popularity; however, the number of repetitions in comparison with traditional therapy methods has yet to be investigated. The primary purpose of this study was to document and compare the number of repetitions performed while playing 1 of 2 video gaming systems for a time frame similar to that of a traditional therapy session in individuals with chronic stroke. Twelve participants with chronic stroke (mean age, 66.8 ± 8.2 years; time poststroke, 19.2 ± 15.4 months) completed video game play sessions, using either the Nintendo Wii or the Playstation 2 EyeToy. A total of 203 sessions were captured on video record; of these, 50 sessions for each gaming system were randomly selected for analysis. For each selected record, active upper and lower extremity repetitions were counted for a 36-minute segment of the recorded session. The Playstation 2 EyeToy group produced an average of 302.5 (228.1) upper extremity active movements and 189.3 (98.3) weight shifts, significantly higher than the Nintendo Wii group, which produced an average of 61.9 (65.7) upper extremity active movements and 109.7 (78.5) weight shifts. No significant differences were found in steps and other lower extremity active movements between the 2 systems. The Playstation 2 EyeToy group produced more upper extremity active movements and weight shifting movements than the Nintendo Wii group; the number and type of repetitions varied across games. Active gaming (specifically Playstation 2 EyeToy) provided more upper extremity repetitions than those reported in the literature by using traditional therapy, suggesting that it may be a modality to promote increased active movements in individuals poststroke.


Relationship among age, insulin resistance, and blood pressure.
The effect of age to modify the relationship between insulin resistance and hypertension is unclear. In this retrospective, cross-sectional study, median age was used to create two age groups (<52 vs. ≥52 years), and comparisons were made of metabolic characteristics, including steady-state plasma glucose (SSPG) concentrations measured during the insulin suppression test to quantify insulin resistance. Individuals were stratified into SSPG tertiles and categorized as having normal blood pressure (BP), prehypertension, or hypertension. SSPG concentrations were similar in the two age groups (161 vs. 164 mg/dL). In the most insulin-resistant tertile, distribution of normal BP, prehypertension, and hypertension was equal in those aged <52 years, whereas in those aged ≥52 years, prevalence of hypertension was increased approximately fivefold compared with those with normal BP. Multivariate regression analysis demonstrated significant interaction between age and SSPG in predicting systolic BP (P = .023). In stratified analysis, SSPG, but not age, was an independent predictor of systolic BP and diastolic BP in ≥52 years group, whereas the reverse was true in the younger group. The adverse impact of insulin resistance on BP was accentuated in older individuals and may have a greater impact than further aging.


The RAPIDO trial-Reduction in disease-related treatment failure does not translate into improved overall survival: a mystery solved!
The initial publication of the RAPIDO trial resulted in widespread adoption of short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer. The impressive reduction in disease-related treatment failure did not, however, translate into any overall survival benefit. The recent update of the RAPIDO trial with its 5-year results provides much insight into the actual effect that this approach has on patient outcomes and the detriment in local control leads to the question as to whether this approach can still be considered as standard of care in high-risk rectal cancer.


Learning to match auditory and visual speech cues: social influences on acquisition of phonological categories.
Infants' language exposure largely involves face-to-face interactions providing acoustic and visual speech cues but also social cues that might foster language learning. Yet, both audiovisual speech information and social information have so far received little attention in research on infants' early language development. Using a preferential looking paradigm, 44 German 6-month olds' ability to detect mismatches between concurrently presented auditory and visual native vowels was tested. Outcomes were related to mothers' speech style and interactive behavior assessed during free play with their infant, and to infant-specific factors assessed through a questionnaire. Results show that mothers' and infants' social behavior modulated infants' preference for matching audiovisual speech. Moreover, infants' audiovisual speech perception correlated with later vocabulary size, suggesting a lasting effect on language development.


Characterization and idiotypic analysis of an anti-RNP monoclonal antibody.
To investigate mechanisms of anti-RNP antibody expression in autoimmune disease, idiotypes of a monoclonal anti-RNP of murine origin were analysed. This antibody, designated 4L1, was obtained from a MRL-lpr/lpr mouse and shown to have anti-RNP specificity by gel analysis of radiolabelled cellular RNA. An anti-idiotypic antiserum was prepared in a rabbit to 4L1 and rendered specific for idiotype by absorption with IgG from B6 mice and two BALB/c myelomas of the same chain composition as 4L1 (IgM kappa). In competition ELISA assays, this antiserum detected idiotypes commonly expressed in sera of MRL-lpr/lpr mice irrespective of the presence of anti-RNP. These idiotypes were not exclusive to this autoimmune strain, however, and could also be identified in normal mice. To identify other antibodies with this idiotype, a panel of MRL hybridomas was tested. This analysis demonstrated idiotypic cross-reactivity between 4L1 and two anti-Sm monoclonal antibodies derived from another animal. These results suggest that 4L1 belongs to a larger idiotype bearing family only some of whose members may have aberrant expression.


Interprofessional collaboration in primary health care: a review of facilitators and barriers perceived by involved actors.
The epidemiological transition calls for redefining the roles of the various professionals involved in primary health care towards greater collaboration. We aimed to identify facilitators of, and barriers to, interprofessional collaboration in primary health care as perceived by the actors involved, other than nurses. Systematic review using synthetic thematic analysis of qualitative research. Articles were retrieved from Medline, Web of science, Psychinfo and The Cochrane library up to July 2013. Quality and relevance of the studies were assessed according to the Dixon-Woods criteria. The following stakeholders were targeted: general practitioners, pharmacists, mental health workers, midwives, physiotherapists, social workers and receptionists. Forty-four articles were included. The principal facilitator of interprofessional collaboration in primary care was the different actors' common interest in collaboration, perceiving opportunities to improve quality of care and to develop new professional fields. The main barriers were the challenges of definition and awareness of one another's roles and competences, shared information, confidentiality and responsibility, team building and interprofessional training, long-term funding and joint monitoring. Interprofessional organization and training based on appropriate models should support collaboration development. The active participation of the patient is required to go beyond professional boundaries and hierarchies. Multidisciplinary research projects are recommended.


Evolutionary conservation of molecular structure and antiviral function of a viral receptor, LGP2, in amphioxus Branchiostoma japonicum.
RIG-I-like (where RIG-I is retinoic acid inducible gene I) receptor LGP2 (where LGP2 is laboratory of genetics and physiology) is an important intracellular receptor that recognizes viral RNAs in innate immunity, but its origin and evolution remains unknown. Here we clearly demonstrate the presence of a RIG-I-like receptor, BjLGP2, in the basal chordate amphioxus. It is predominantly expressed in the hepatic caecum and hindgut, and is upregulated following challenge with poly(I:C). BjLGP2 is distributed in the cytoplasm of both grouper spleen and flounder gill (FG) cells, and the recombinant BjLGP2 interacts with poly(I:C). BjLGP2 can enhance the expression of IFN and IFN-inducible genes in FG cells upon poly(I:C) challenge. It also significantly induces the expression of the antiviral genes ifn-i and Mx as well as the signal transduction relevant genes MAVS, NF-κB, and IRF-3 in FG cells upon lymphocystis disease virus challenge. Moreover, BjLGP2 inhibits the replication of lymphocystis disease virus in FG cells and the gene transcription of Singapore grouper iridovirus in grouper spleen cells. This is the first report showing that a LGP2 protein in invertebrate species (amphioxus) is structurally conserved and plays an antiviral role similar to that of vertebrate LGP2 proteins.


Characteristic chromatographic fingerprint study of short-chain fatty acids in human milk, infant formula, pure milk and fermented milk by gas chromatography-mass spectrometry.
Human milk, infant formula, pure milk and fermented milk as food products or dietary supplements provide a range of nutrients required to both infants and adults. Recently, a growing body of evidence has revealed the beneficial roles of short-chain fatty acids (SCFAs), a subset of fatty acids produced from the fermentation of dietary fibers by gut microbiota. The objective of this study was to establish a chromatographic fingerprint technique to investigate SCFAs in human milk and dairy products by gas chromatography coupled with mass spectrometry. The multivariate method for principal component analysis assessed differences between milk types. Human milk, infant formula, pure milk and fermented milk were grouped independently, mainly because of differences in formic acid, acetic acid, propionic acid and hexanoic acid levels. This method will be important for the assessment of SCFAs in human milk and various dairy products.


Urinoma (para-ureteral pseudocyst) as a consequence of trauma in a cat.
A two-year-old cat was involved in a road traffic accident. Survey abdominal radiographs and urinary function were considered unremarkable. Six weeks later the cat presented with a palpable dorsal abdominal mass. Radiography revealed a soft tissue opacity mass caudal to the right kidney. Ultrasonography revealed a cyst-like structure with moderately echogenic contents, and right-sided hydronephrosis. There was no excretion of contrast medium from the right kidney after intravenous urography. Surgery revealed a disrupted right ureter adherent to the retroperitoneal mass. The mass contained serosanguineous fluid consistent with extravasated urine. Ureteronephrectomy was performed. The majority of the mass was excised and the cavity ablated. Histopathology of the excised tissue revealed a thick fibrous wall with no epithelial lining, consistent with a urinoma, which is thought to have developed as a consequence of ureteral trauma. The cat was clinically well three months postoperatively.


Cyclizidine-Type Alkaloids from Streptomyces sp. HNA39.
Eight new cyclizidine-type alkaloids (1-8) and one known alkaloid (9) were identified from the chemical investigations of a marine-derived actinomycete, Streptomyces sp. HNA39. Among these alkaloids, compounds 3, 7, and 8 contain a chlorine atom, and the known alkaloid, (+)-ent-cyclizidine (9), is now first reported as a natural product. Their structures were elucidated by extensive NMR-spectroscopic analysis and HRESIMS data. The absolute configurations of all of the compounds were established by ECD calculations. Cytotoxicity evaluations of all of the compounds showed that compound 2 exhibited significant activity against the PC3 and HCT116 human-cancer-cell lines with IC50 values of 0.52 ± 0.03 and 8.3 ± 0.1 μM, respectively. Interestingly, compounds 2, 5, 7, and 8 exhibited moderate inhibition against the ROCK2 protein kinase with IC50 values from 7.0 ± 0.8 to 42 ± 3 μM.


[Modeling of vitreoretinal proliferation].
Complexes of endogenous immunopeptides produced by autologous peripheral blood lymphocytes were injected to the vitreous body of 17 chinchilla rabbits (34 eyes). The agents injected were autosupernatant. L fraction containing molecular substances with mol. weight of 40,000 to 60,000 D, and M fraction containing substances with mol. weight of 15,000 to 30,000 D. Clinical and morphologic studies demonstrated that injection of endogenous immunopeptides led to active lymphoid inflammatory infiltration associated with proliferation and formation of new vessels. In contrast to the M fraction, the exudative processes triggered by the L fraction were more definitely localized and associated with the appearance of fibroplastic cords (the proliferative component). The models created may be used for the development of methods for prevention and treatment of vitreoretinal proliferation.


Characterization of a recombinant molecule covalently indistinguishable from human cerebroside-sulfate activator protein (CSAct or Saposin B).
Humans deficient in the cerebroside-sulfate activator protein (CSAct or Saposin B) are unable to catabolize sulfatide and other glycosphingolipids leading to their accumulation and neurodegenerative disease. Clinically this usually manifests as a form of metachromatic leukodystrophy (MLD). CSAct is a small water-soluble glycoprotein that apparently functions in the lysosome to solubilize sulfatide and other lipids enabling their interaction with soluble lysosomal hydrolases. CSAct activity can be measured in vitro by assay of its ability to activate sulfatide-sulfate hydrolysis by arylsulfatase A or ex vivo by its ability to functionally complement CSAct deficient fibroblast cell lines derived from MLD patients. A recombinant form of CSAct has been expressed in E. coli and processed in vitro to a form covalently indistinguishable from deglycosylated human CSAct isolated from human urine. Size-exclusion chromatography in combination with multi-angle laser-light scattering (SEC-MALLS) measurements demonstrate that both native and recombinant forms of the molecule behave as a dimer in the pH range 7.0-4.5. The CSAct activity assay showed that both recombinant and deglycosylated human urine CSAct efficiently activated sulfatide sulfate hydrolysis and provided functional complementation of CSAct-deficient cells. However, a D21N mutant form of recombinant CSAct could not functionally complement these cells despite full activity in the in vitro assay. It is concluded that while glycosylation is unnecessary for in vitro and ex vivo activity of CSAct, modification of the native N21 is necessary to prevent loss of ex vivo activity, possibly via protection from degradation.


CDK20 interacts with KEAP1 to activate NRF2 and promotes radiochemoresistance in lung cancer cells.
Radiochemoresistance is considered the main cause of local recurrence and distant metastasis in lung cancer. However, the underlying mechanisms of radiochemoresistance remain to be uncovered. In this study, we determine the functions of cell cycle-related kinase (CDK20) in radiochemoresistance. CDK20 is a newly identified protein kinase, which plays critical roles in cell growth and proliferation in several types of cancer. Using tandem affinity purification technology, we provide evidences that CDK20 binds to the ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1), which targets transcriptional factor nuclear factor erythroid-2-related factor 2 (NRF2) for degradation. We show that this interaction is mediated by an evolutionarily conserved ETGE motif on CDK20. Furthermore, we demonstrate that CDK20 competes with NRF2 for KEAP1 binding, enhances the transcriptional activity of NRF2 and lowers the cellular reactive oxygen species level. Moreover, CDK20-depleted cells display impaired cell proliferation, defective G2/M arrest and increased radiochemosensitivity in lung cancer. These phenotypes induced by CDK20 knockdown are partially dependent on NRF2 inactivation. More importantly, CDK20 is overexpressed in human lung cancer tissues, as determined by immunostaining. Collectively, our results suggest that CDK20 positively modulate the KEAP1-NRF2 cytoprotective pathway to regulate tumor progression and radiochemoresistance, implying that CDK20 is a novel, promising therapeutic target for lung cancer.


A Case Report of Large Bowel Obstruction in a Patient With an Inflatable Penile Prosthesis.
Inflatable penile prostheses (IPP) consist of 2 cylinders implanted into the corpora cavernosa, a pump placed in the scrotum, and a saline-filled reservoir traditionally placed in the space of Retzius. IPPs are used to treat refractory erectile dysfunction with few rare, but serious, complications. Cases of reservoirs causing erosion into the bladder, small bowel obstructions, vascular compression, and inguinal herniation have been described. We highlight the importance of keeping a broad differential diagnosis when assessing patients with bowel obstructions. A 68-year-old man with a previous IPP placement presented with left lower quadrant abdominal pain, constipation and obstipation for 5 days. On exam, he was afebrile, and noted to have a firm, distended, tympanic abdomen. CT scan showed a distended cecum at 11 cm, narrowing of the proximal sigmoid with adjacent inflammatory changes, and minimal peri-colonic air, suggestive of a localized perforation. The IPP reservoir was seen in the left iliac fossa, coinciding with the lead point of the obstruction, suggesting that the reservoir may have itself caused the obstruction. The patient was taken to the operating room for an emergent exploratory laparotomy, which revealed a mass in the colon abutting the IPP reservoir. Considerations for IPP component explantation, factors considered for reintervention, and preservation of penile length with avoidance of penile fibrosis. A left colectomy with transverse colostomy was successfully performed and the IPP reservoir was explanted. Intraoperative frozen section revealed adenocarcinoma. Upon initial review of the imaging, it was thought that the IPP reservoir may have caused the obstruction, but intraoperatively, the colonic tumor was found to be the culprit. Although complications related to IPPs, including bowel obstructions, have been previously described in the literature, treatment for large bowel obstructions must take into account all possible etiologies, including malignancy. Atri E, Mallory C, Perez A, et al. A Case Report of Large Bowel Obstruction in a Patient With an Inflatable Penile Prosthesis. Sex Med 2021;9:100391.


Iris neovascular tufts.
Iris neovascular tufts are biomicroscopic capillary outgrowths from the pupillary margins. Iris tufts have been reported to occur in the elderly, in diabetes patients, and in myotonic dystrophy patients. Three cases have also been described in association with retinal vein occlusion. This paper describes a patient with unilateral acute retinal branch vein occlusion who had bilateral iris neovascular tufts. The bilaterality of this elderly patient's tufts suggested an underlying acquired systemic disorder. The patient denied medical illness, except for hypertension. Medical evaluation disclosed an insulin tolerance test diagnostic of diabetes, although a glucose tolerance test was not markedly abnormal. Iris tufts appeared to be associated with abnormal insulin secretion. Their occurrence with branch vein occlusion may be coincidental.


Low-temperature clean-up method for the determination of pyrethroids in milk using gas chromatography with electron capture detection.
This paper describes a new gas-chromatography with electron capture detection (GC-ECD) method for determination of some pyrethroids in milk samples. The extraction of the pyrethroids was carried out by liquid-liquid extraction with clean-up by precipitation at low temperature, without additional stages for removal of fat interferences. The method was efficient with recoveries of 93.0+/-0.1% for cipermethrin and 84.0+/-0.3% for deltamethrin. The quantification limits were 0.75 microg L(-1) for both pyrethroids. The method was simple, of easy execution, and used only small quantities of organic solvent. After optimization and validation, the method was used for the determination of residues of the pyrethroids cipermethrin and deltamethrin in milk and in lactea drink commercialized in Viçosa (MG, Brazil). Some samples presented contamination with deltamethrin at levels below the maximum contamination limits established by the FAO.


Neglected foreign body aspiration mimicking bronchial carcinoma.
Foreign body aspiration can occur in any age group, but it is more commonly seen in children. In adults, there is usually a predisposing condition that poses a risk of aspiration. If aspiration occurs, prompt diagnosis and extraction of the foreign body is needed to prevent early and late complications. We report a rare case of neglected foreign body aspiration in a 45-year-old schizophrenic opium addicted patient, which resulted in an occlusive lesion in the bronchus, mimicking bronchial carcinoma.


A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: a Gynecologic Oncology Group study.
A phase II trial was performed to evaluate the efficacy and safety of gefitinib in patients with persistent/recurrent endometrial cancer. Women with histologically confirmed persistent/recurrent endometrial cancer were treated with 500mg oral gefitinib daily until progression or severe toxicity, with progression-free survival (PFS) at six months as the primary endpoint. Tumor expression of total epidermal growth factor receptor (EGFR), estrogen receptor (ER), progesterone receptor A (PRA) and B (PRB), Ki67, pEGFR and activated extracellular signal-regulated kinase (pERK) were examined pre- and post-treatment. EGFR was sequenced, and serum concentrations of soluble EGFR (sEGFR) at baseline also were examined. Of 29 patients enrolled, 26 were evaluable for efficacy and toxicity. Four patients experienced PFS ≥6 months, and one had a complete response which was not associated with an EGFR mutation. The concentration of sEGFR in pretreatment serum was positively correlated with overall survival (OS), but not with responsiveness to gefitinib in this small patient cohort. Expression of tumor biomarkers was not associated with PFS or OS. Co-expression of ER with PRA in primary and recurrent tumors, and pEGFR with pERK in primary tumors was observed. This treatment regimen was tolerable but lacked sufficient efficacy to warrant further evaluation in this setting. The possible association between serum sEGFR concentrations and OS, and temporal changes in expression of pEGFR and pERK and the documented CR of one patient are interesting and warrant additional investigation.