Morphology of congenital microphthalmia in chicks (Gallus gallus).
This study examines the morphology of sporadic congenital microphthalmia in 1-day-old chicks, with particular emphasis on the neural retina. On the basis of the size of the eyeball it is possible to classify microphthalmia into two groups, severe and mild. In severe microphthalmia (less than 5 mm in equatorial diameter), the eyeball is severely malformed, but in most cases it shows evidence of an organized neural retina. Although ganglion cells and an optic nerve head are present in a small proportion of these retinae, we could not trace an optic nerve projection to the brain. These results indicate that some ganglion cells are able to be sustained after the period of naturally occurring cell death, suggesting either that those ganglion cells have established some contact with the central nervous system or that the presence of their axons in a rudimentary optic nerve is adequate for survival. In mild microphthalmia (greater than 5 mm in equatorial diameter), the most consistent abnormality is a defect in the pecten, which together with other abnormalities such as orbital cysts and colobomas indicates that the major abnormality occurs in the region of the choroid fissure. Associated with these defects are abnormalities within the ganglion cell layer. In some cases the number of ganglion cells was reduced, and in others the numbers of both ganglion and displaced amacrine cells were reduced. Unexpectedly, there were localized regions completely devoid of cells in the ganglion cell layer. The timing of the congenital defect may provide some clue as to the presence of a critical period in which displaced amacrine cells are formed or are sensitive to events related to ganglion cell loss.


[Role of oxidative stress in respiratory diseases and its monitoring].
Together with inflammation and subsequent remodeling of airways, an imbalance between oxidative and anti-oxidative agents is generated during the development of numerous pulmonary diseases. This process seems to be involved in both the pathogenesis and chronification of asthma, chronic obstructive pulmonary disease (COPD), SOAS, interstitial lung diseases and cystic fibrosis. Reactive oxygen species including superoxide anion, hidroxyl radicals and hydrogen peroxide (H2O2) are synthetised as a response of inflammatory cells and are responsible of the oxidation of nucleic acids, proteins and membrane lipids, leading to cell damage and enhanced inflammation. Until recently, it was difficult to quantify the airway production of reactive oxidative species (ROS). In fact, it has been only in the last few years when it has been possible to determine indirectly the levels of ROS in expired air and in tissue of asthmatic patients. The analysis of exhaled air is a single, reproducible and non-invasive technique which is useful in the study of volatile and non-volatile gases generated in different conditions. The determination of exhaled nitric oxide and carbon monoxide (CO) has a great usefulness in the assessment of asthma. Nitric oxide seems to be closely related to the physiopathology of asthma and COPD. In fact, it is correlated with the levels of sputum eosinophils and with the response to the treatment with steroids. Yet a correlation with the degree of airflow obstruction and the seriousness of the process has not been found. Exhaled CO is another indirect marker of inflammation and it is increased in asthma, COPD, cystic fibrosis and bronchectases. Even though numerous studies have shown its usefulness as a marker of inflammation and in the response to corticosteroids, its clinical application has limitations. In particular, it is not a specific and exclusive marker of oxidative stress and its levels are highly influenced by tobacco smoke. On the other hand, the association between exhaled CO and FEV1 is not clear and no relationship has been proved so far with the improvement of pulmonary function after steroid therapy and with the decrease of maximum expiratory flow at relapses. In this Review, we describe the advances in the knowledge of oxidative stress as a decisive factor in the pathogenesis of prevalent pulmonary diseases, as well as the methods allowing its analysis and monitoring.


Life-Long Genetic and Functional Access to Neural Circuits Using Self-Inactivating Rabies Virus.
Neural networks are emerging as the fundamental computational unit of the brain and it is becoming progressively clearer that network dysfunction is at the core of a number of psychiatric and neurodegenerative disorders. Yet, our ability to target specific networks for functional or genetic manipulations remains limited. Monosynaptically restricted rabies virus facilitates the anatomical investigation of neural circuits. However, the inherent cytotoxicity of the rabies largely prevents its implementation in long-term functional studies and the genetic manipulation of neural networks. To overcome this limitation, we developed a self-inactivating ΔG-rabies virus (SiR) that transcriptionally disappears from the infected neurons while leaving permanent genetic access to the traced network. SiR provides a virtually unlimited temporal window for the study of network dynamics and for the genetic and functional manipulation of neural circuits in vivo without adverse effects on neuronal physiology and circuit function.


An unusual hormonal cause of hypertension and hypokalaemia.
A patient with primary hyperparathyroidism who presented with hypokalaemia and hypertension is described. Renal potassium wasting was documented and cured by removal of a parathyroid adenoma. Possible mechanisms for this unusual manifestation of hyperparathyroidism are mentioned. Other features of the case were severe anaemia, nephrocalcinosis, pseudogout and postoperative acidosis.


Retrospective Analysis of Laparoscopic Partial Nephrectomies Using the Zero Ischemia Technique.
To report a series of 89 off-clamp laparoscopic partial nephrectomies (LPN) performed without using any additional "nephron sparing" manipulations. Retrospective analysis of surgical characteristics, complications, postoperative results, and renal function changes. Between March 2008 and May 2014, 89 LPN using zero ischemia technique were performed. Most of the patients (61.8%) were male. The median age was 62 years (23-88). The mean BMI was 27.5 kg/m2 (20.8-54.2). The median tumor size was 3.0 cm (1.0-8.0). Tumor location was upper, middle, and lower part of the kidney in 33 (37.0%), 42 (47.2%), and 14 (15.7%) of patients, respectively. The median operative time was 154 min (58-289). The median hemoglobin change was -1.6 g/dL (0.5-5.5). The transfusion rate was 7.9%. The mean preoperative glomerular filtration rate was 96.6 mL/min (21.5-180.0) with a mean postoperative decline of 6.52 mL/min. The mean creatinine elevation after LPN was 0.09 mg/dL. The median hospital stay was 6 days (2-24). The intraoperative complications rate was 2.3%. Early postoperative complication rate was 33.7%. Late complications occurred in 6.7%. In 7 cases (7.9%), the surgical margins were microscopically involved by tumor cells. Conversion rate was 3.4%. Data obtained in the current series show that laparoscopic partial nephrectomy can be successfully performed without hilar clamping. Our results are comparable with contemporary data. Larger prospective studies would be helpful in assessing the evidence-based advantages of the "zero ischemia" technique.


The Effect of Age on Postoperative Morbidity in Women Undergoing Urogynecologic Surgery.
The objectives of this study were to estimate the effect of older age on postoperative morbidity and to assess other factors associated with postoperative complications after urogynecologic surgery. We conducted a retrospective cohort study of 508 women who underwent pelvic floor reconstructive surgery between March 2011 and June 2013. Our 2 cohorts were based on age--women younger than 65 years and women aged 65 years or older. Our primary outcome was clinically significant postoperative complications defined as Dindo-Clavien grade greater than or equal to 2. We compared the risk of postoperative morbidity between the cohorts and constructed a logistic regression analysis to adjust for potential confounders. Of the 508 patients, 300 (59.1%) were in the younger cohort and 208 (40.9%) were in the older cohort. For our primary outcome, we found that older women had a significantly higher rate of clinically significant postoperative complications (12.5% vs. 6.7%, P = 0.02). In a multivariate logistic regression model that included advanced prolapse, smoking status, Charlson Comorbidity Index, body mass index, and operative time, older age remained significantly associated with greater postoperative morbidity (odds ratio, 2.06; 95% confidence interval, 1.03-4.11). The length of surgery in hours was also associated with greater morbidity (odds ratio, 1.47; 95% confidence interval, 1.14-1.66). Women aged 65 years and older who underwent urogynecologic surgery had a higher risk of clinically significant postoperative complications based on the Dindo-Clavien Scale when compared with women younger than 65 years.


[Endoscopic gallbladder stenting for acute cholecystitis].
Acute cholecystitis is an inflammatory disease of the gallbladder. Inflammation often remains in the gallbladder, but some patients may take a fatal course with exacerbation of inflammation. Although laparoscopic cholecystectomy is recommended for moderate and severe acute cystitis, sometimes cholecystectomy is impossible in elder patients. Because many elder patients have bad general conditions, cholecystectomy should not be performed. Such patients are generally treated by percutaneous transhepatic gallbladder drainage (PTGBD), but PTGBD has the risk of intra-abdominal bleeding. In previous reports, endoscopic gallbladder stenting (EGBS) has been shown to be an effective strategy in cirrhosis patients with symptomatic cholelithiasis as a bridge to transplantation. Recent studies on EGBS have demonstrated an effective long-term management of acute cholecystitis in elderly patients who are poor surgical candidates. Here, we reviewed EGBS for the management of acute cholecystitis.


The collaborative phenotype of secondary B cells is determined by T lymphocytes during in vivo immunization.
Previous studies have demonstrated that the B cells in immune and nonimmune mice manifest different major histocompatibility complex (MHC) collaborative phenotypes with antigen-specific T cells. Immune, or secondary B cells require syngeneic-like MHC recognition by collaborating T cells, and in its absence fail to be stimulated. Primary B cells manifest a much less stringent requisite for MHC recognition by T cells, and under conditions in which secondary B cells fail to be stimulated, primary B cells are stimulated to secrete IgM antibody. Experiments were conducted to determine whether the acquisition of the secondary B cells' MHC collaborative phenotype was dependent on the presence of T cells during in vivo immunization. B cell populations from T dependently and T independently immunized conventional BALB/c and athymic BALB/c nu/nu mice were compared in their ability to collaborate with allogeneic T cells. Although antigen alone promotes the differentiation of several secondary B cell characteristics, including an increase in the frequency of antigen-specific B cells and a preference for IgG1 antibody synthesis in vitro, the acquisition of the secondary B cells' MHC collaborative phenotype was dependent on the presence of T cells during in vivo immunization. B cell populations from T dependently and T independently immunized conventional BALB/c and athymic BALB/c nu/nu mice were compared in their ability to collaborate with allogeneic T cells. Although antigen alone promotes the differentiation of several secondary B cell characteristics, including an increase in the frequency of antigen-specific B cells and a preference of IgG1 antibody synthesis in vitro, the acquisition of the secondary B cells' MHC collaborative phenotype was found to be dependent on the presence of T cells during in vivo immunization. Thus, the restriction imposed on T cell-B-cell-collaborative interactions in secondary humoral immune responses appears to be the result of T dependent antigen-driven events.


Chemotherapy regimen is associated with venous thromboembolism risk in patients with urothelial tract cancer.
To assess the association of venous thromboembolism (VTE) with different chemotherapy regimens in patients with urothelial tract cancer. We identified patients aged ≥66 years, diagnosed with urothelial tract cancer in the period 1998 to 2011 in the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database. The chemotherapy regimens analysed were gemcitabine/cisplatin (GC), methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), or gemcitabine/carboplatin (CarboG). Propensity scores for treatment regimen based on comorbidities, tumour characteristics, age, and year of diagnosis were calculated. VTE rates within 120 days of chemotherapy initiation were calculated. VTE risk stratified by chemotherapy regimen was modelled using multivariable logistic regression, adjusting for treatment propensity scores and additional demographic characteristics. Overall survival stratified by VTE and chemotherapy regimen was estimated using Kaplan-Meier methods and the log-rank test. Of 5594 identified patients, a VTE occurred in 13.0%. The VTE rates within 120 days of chemotherapy initiation were 15.3% for GC, 8.7% for MVAC, and 12.0% for CarboG. On multivariable analysis, MVAC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.94) and CarboG (OR 0.71, 95% CI: 0.59-0.85) were associated with lower VTE risk compared with GC. VTE was associated with worse overall survival (P < 0.001). Compared with GC, MVAC and CarboG were associated with a lower rate of VTE. This finding suggests that gemcitabine may add to the increased thrombosis risk from cisplatin. Additionally, patients with a VTE had worse survival outcomes than those without a VTE. Analysis of the risk of blood clots with different chemotherapy regimens in patients with urothelial tract cancer showed that GC was associated with the highest rate. We also found that blood clots were associated with worse patient outcomes.


[Sitosterolemia (phytosterolemia)].
Sitosterolemia or phytosterolemia is a rare autosomal recessive hereditary lipid storage disorder. It is caused by homozygous or compound heterozygous mutations in one of the two ABCG5 and ABCG8 genes encoding the intestinal and hepatic heterodimer ABCG5 (sterolin 1)/ABCG8 (sterolin 2) efflux transporters. These mutations lead to intestinal hyperabsorption and reduced hepatic secretion of cholesterol and plant sterols with subsequent accumulation of phytosterols and cholesterol in plasma and deposition in tissue (xanthoma). Phytosterols are found mainly in vegetable oils, margarine, nuts, grains, soybeans and avocados. Patients with sitosterolemia show extreme phenotypic heterogeneity from almost asymptomatic individuals to those with combined severe hypercholesterolemia at a young age, leading to increased atherosclerosis and premature cardiac death. Early abnormalities include hemolytic anemia with stomatocytosis, macrothrombocytopenia and splenomegaly. In addition to strict avoidance of phytosterol-containing foods, the use of the sterol absorption inhibitor ezetimibe, possibly in combination with the bile acid-binding resin cholestyramine, is the most effective treatment option.


Who, When, How, and Why Bystanders Intervene in Physical and Psychological Teen Dating Violence.
Teen dating violence victimization is associated with a host of adverse mental and physical health problems. A number of bystander-focused interventions have been developed to mitigate the occurrence of abuse but with varying effectiveness. There remains a need to understand more about bystander behaviors used by adolescents to ensure that existing intervention components match with bystanders' attitudes and behaviors about intervening. The current study is a scoping review of existing literature on adolescents' use of bystander behaviors to determine who, when, how, and why adolescents intervene. Seventeen articles met inclusion criteria, the majority of which used qualitative or observational survey designs. Adolescents who either feel a sense of responsibility and confidence to intervene or are directly involved with or know the individuals involved in the dating violence are more likely to intervene. Adolescents intervene when they are able to define an act as dating violence and tend to intervene when the victim is female and when they have a supportive relationship with at least one teacher in their school. The various ways how bystander intervention is engaged in ranges from verbally or physically confronting the abuser, distracting the abuser, seeking support from an adult, to passively accepting the abuse. Reasons why adolescents intervene include believing the abuse is wrong and that intervening will diffuse the situation and help the victim. A number of barriers to bystander intervention emerged from analysis including individual attitudes and school climate factors. Implications for strengthening bystander intervention programs are discussed.


CRP (C-reactive protein) in Early Pregnancy Predictor for Development of GDM.
This case-control study was done to find out whether elevated serum CRP in early pregnancy is a predictor of GDM and conducted under joined supervision of Obstetrics & Gynecology Department, Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital and Biomedical Research Group (BMRG), BIRDEM, from August 2005 to November 2007. Pregnant mothers at their first 16 weeks of gestation without any medical disorder of pregnancy were included in the study. For the purpose of this study blood samples were again collected for OGTT at their 16weeks, 24-28 weeks and 32 weeks of pregnancy to detect GDM. After confirmation of GDM, C-reactive protein and C-peptide were done from the preserved fasting serum sample at the end of this study to compare GDM with control group. A total of 297 patients were included in this study. Among them 145(48%) patients completed follow up, 59(20%) lost from follow-up and 11(4%) patients had abortion; 82(28%) are due for follow up 31(10%) pregnant patients developed GDM subsequently. Finally 28 GDM patients were taken as cases and 71 were control matched for their gestational age and parity. At earlier weeks of gestation, hsCRP could predict (PPV) development of GDM in 59% with NPV 84%, sensitivity 61% and specificity 83%. C-peptide in the 50th percentile could predict (PPV) development of GDM in 58% with NPV 96%, sensitivity 72% and specificity 93%. The present data indicates that hsCRP and C-peptide both is sensitive markers in predicting GDM.


Cardiopulmonary responses of asthmatic children to strenuous exercise. Effect of theophylline.
The purpose of the study were to investigate the cardiopulmonary adaptations of asthmatic children to physical exercise and to evaluate the effects of theophylline. Two groups of children were evaluated. Eight asthmatic children participated in two exercise sessions. Half of the patients received theophylline in predetermined doses during the first session and half prior to the second session. Seventeen normal children matched for age, height, and weight served as controls. Various cardiorespiratory parameters were measured every 2 minutes during exercise and prior to termination of maximal physical effort. The results indicate that children with chronic asthma reach the range of predicted maximal aerobic capacity for their age. Theophylline increases the endurance of asthmatic children to maximal physical efforts without improving the cardiorespiratory parameters that were measured. The use of theophylline in therapeutic doses appears safe under conditions of vigorous exercise.


Up-regulation of lipid metabolism and glycine betaine synthesis are associated with choline-induced salt tolerance in halophytic seashore paspalum.
Choline may affect salt tolerance by regulating lipid and glycine betaine (GB) metabolism. This study was conducted to determine whether alteration of lipid profiles and GB metabolism may contribute to choline regulation and genotypic variations in salt tolerance in a halophytic grass, seashore paspalum (Paspalum vaginatum). Plants of Adalayd and Sea Isle 2000 were subjected to salt stress (200-mM NaCl) with or without foliar application of choline chloride (1 mM). Genotypic variations in salt tolerance and promotive effects of choline application on salt tolerance were associated with both the up-regulation of lipid metabolism and GB synthesis. The genotypic variations in salt tolerance associated with lipid metabolism were reflected by the differential accumulation of phosphatidylcholine and phosphatidylethanolamine between Adalayd and Sea Isle 2000. Choline-induced salt tolerance was associated with of the increase in digalactosyl diacylglycerol (DGDG) content including DGDG (36:4 and 36:6) in both cultivars of seashore paspalum and enhanced synthesis of phosphatidylinositol (34:2, 36:5, and 36:2) and phosphatidic acid (34:2, 34:1, and 36:5), as well as increases in the ratio of digalactosyl diacylglycerol: monogalactosyl diacylglycerol (DGDG:MGDG) in salt-tolerant Sea Isle 2000. Choline regulation of salt tolerance may be due to the alteration in lipid metabolism in this halophytic grass species.


Contribution of caspase-independent pathway to apoptosis in malignant glioma induced by carbon ion beams.
High linear energy transfer (LET) carbon ion beam (CIB) is becoming the best tool for external radiotherapy of inoperable tumors because of its greater cell killing than conventional low LET gamma or X-rays. In the present study, whether the caspase-independent pathway exerts the important contribution in CIB-induced cell apoptosis was explored. Herein we showed, despite the absence of caspase activity using a pan caspase inhibitor Z-VAD-FMK, that apoptosis induced by high LET CIB were clearly observed in the glioma cells. Simultaneously, the increased 8-OHdG level, PARP-1 activity and AIF translocation occurred in response to CIB irradiation. Moreover, it was distinctly higher in the nuclear translocation frequency along with PARP-1 activation when the caspase protease cascade was suppressed in the irradiated glioma cells. Nuclear colocalization between PARP-1 and AIF as well as a positive association of the PARP-1 mRNA expression with AIF translocation frequency indicated that PARP-1 activation controlled the translocation of AIF to the nucleus. Our findings strongly demonstrated that caspase-independent cell apoptosis provided a prominent compensation in the glioma cell death involving the PARP-1/AIF signaling pathway at 24 h after CIB exposure, and likely triggered by oxidative damage to DNA. The knowledge on the molecular mechanism of AIF-mediated cell death may be very useful for the improvement of the therapeutic efficacy of malignant gliomas with heavy charged particles.


Hypercoagulable state leading to paraplegia in a middle-aged man.
A 37-year-old man presented with an unusual thrombotic disorder characterized by acute paraplegia and the absence of palpable pulses due to extensive arterial thrombosis of the aorta and its distal branches. The patient had an extremely complicated course that necessitated multiple revascularization procedures over a 1.5-year period. This case is unusual not only because of its complexity but also because of the patient's relatively young age, his lack of risk factors for vascular disease, and the presence of a neurologic deficit that improved when circulation was restored. More unusual, however, is the fact that all diagnoses were excluded except for a high lipoprotein(a) level. To our knowledge, this is the 1st reported case in which aortic thrombosis has been related to hypercoagulability.


AL type cardiac amyloidosis: a devastating fatal disease.
Cardiac amyloidosis is a rare entity with a grave prognosis. Due to the low index of suspicion secondary to non-specific symptoms, it is often diagnosed at an advanced stage with multi-organ involvement. We report a case of systemic AL amyloidosis with predominant cardiac and renal involvement associated with multiple myeloma. A 60-year-old male presented with progressive anasarca, orthopnea and weight gain over 8 months. On clinical examination, 3+ pitting edema was found in bilateral extremities and scrotum. Serum N-type proBNP and troponin T were elevated, and EKG showed diffuse low voltage QRS, right axis deviation, and 1st degree AV block. Echocardiography revealed granular myocardium, biventricular hypertrophy, bi-atrial dilation and apical sparing pattern on global longitudinal strain which was suggestive of cardiac amyloidosis. Light chain assessment showed elevated kappa and lambda chains with kappa to lambda ratio of 16.2. Endomyocardial biopsy revealed AL type cardiac amyloidosis, and bone marrow biopsy confirmed the diagnosis of multiple myeloma. He received six cycles of bortezomib, cyclophosphamide, and dexamethasone but continued to deteriorate. He experienced an episode of cardiac arrest following which he had a return of spontaneous circulation but due to poor prognosis, the family opted for pursuing comfort measures only. Cardiac involvement in AL type amyloidosis imparts significant morbidity and mortality. The management of cardiac amyloidosis entails a multidisciplinary approach with an emphasis on cardiology and oncology. Despite the novel diagnostic modalities and treatment regimens, the outcome for AL-type cardiac amyloidosis remains poor.


Immunohistochemical analysis of prognostic protein markers for primary localized clear cell renal cell carcinoma.
Recurrence is not reliably predictable in localized clear cell renal cell carcinoma. Proteinmarkers could improve predictive accuracy. Tissue-microarrays from 132 patients with primary localized ccRCC were immunohistochemically analyzed for VHL, Ki67, p53, p21, survivin, and, for microvessel-density, UEA-1. Nuclear stainings of Ki67, p21, and survivin were significantly associated with disease-specific survival and increased predictive ability from 74% to 76%, 77%, and 78%, respectively in a multivariate model including T-stage and Fuhrman grade. A score-variable, combining Ki67-, p21-, and nS-staining identified a subset of patients with high risk of disease recurrence and increased predictive ability in the multivariate model to 84%.


Base-Promoted Synthesis of Vinyl Sulfides from Sulfonium Triflates.
A new protocol has been developed for vinyl sulfide synthesis promoted by an alkoxy base under metal-free conditions. In this reaction, aryl and alkenyl sulfonium triflates with diverse functionalities are converted into vinyl sulfides with excellent reactivity. This transformation features mild and safe reaction conditions that avoid catalyst, transition metal, high-pressure gas, and high reaction temperature without compromising efficiency.


Tailless keratins assemble into regular intermediate filaments in vitro.
To study the influence of the non alpha-helical tail domain of keratins in filament formation, we prepared a truncated keratin 8 mutant, K8/tailless. Using site-directed in vitro mutagenesis we introduced a stop codon in the position coding for amino acid number 417 of the K8/wild-type sequence, thereby deleting 86 amino acids of the non alpha-helical tail domain but leaving the consensus sequence at the end of the rod domain intact. Expression of the truncated keratin 8 in Escherichia coli allowed us to purify the protein by a two-step procedure. The filament-forming capacity of the truncated K8 with wild-type K18 and K19 was analyzed using in vitro reconstitution. The in vitro assembly studies with K8/tailless and K18 wild-type indicate that the C-terminal tail domain of a type II keratin, including the homologous subdomain H2, is not required for filament formation. Moreover, reconstitution experiments with K8/tailless and K19, a naturally occurring tailless keratin I, show that the tail domains of type I as well as type II keratins are not an essential requirement for in vitro filament formation. Our results suggest that in vitro filament elongation does not depend on interactions between head and tail domains, although the tail domain might have a role in stabilization of intermediate filaments arising from certain keratin pairs.


Effect of streptozotocin-induced diabetes on electrically evoked erection in the rat.
This study was designed to investigate whether experimental diabetes in rats could functionally affect reflexogenic erection. Erection was elicited by means of electrical stimulation of the dorsal nerves of the penis and recorded as intracorporeal pressure. Rats were examined 1, 3 and 6 months after diabetes induction by streptozotocin. Three and 6 month diabetes caused a significant decrease of latency for erection and a slower phase of detumescence when compared to age-matched controls. In addition, a trend for a lower developed intracorporeal pressure was present in the 6 month diabetes group. Our results indicate that experimental diabetes is associated with alterations of reflexogenic erection.


Hgs Deficiency Caused Restrictive Cardiomyopathy via Disrupting Proteostasis.
The molecular mechanisms underlying restrictive cardiomyopathy (RCM) are not fully understood. Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) is a vital element of Endosomal sorting required for transport (ESCRT), which mediates protein sorting for degradation and is crucial for protein homeostasis (proteostasis) maintenance. However, the physiological function and underlying mechanisms of HGS in RCM are unexplored. We hypothesized that HGS may play vital roles in cardiac homeostasis. Cardiomyocyte-specific Hgs gene knockout mice were generated and developed a phenotype similar to human RCM. Proteomic analysis revealed that Hgs deficiency impaired lysosomal homeostasis in cardiomyocytes. Loss of Hgs disrupted cholesterol transport and lysosomal integrity, resulting in lysosomal storage disorder (LSD) with aberrant autophagosome accumulation and protein aggregation. Suppression of protein aggregation by doxycycline treatment attenuated cardiac fibrosis, and diastolic dysfunction in Hgs-knockout mice. These findings uncovered a novel physiological role of HGS in regulating cardiac lysosomal homeostasis and proteostasis, suggesting that the deficient HGS contributes to LSD-associated RCM-like cardiomyopathy.


Audit of amylase and lipase requests in suspected acute pancreatitis and cost implications, South Africa.
The internationally accepted criteria for the diagnosis of acute pancreatitis (AP) requires two of the three following features to be present: characteristic abdominal pain, elevated serum amylase and/or lipase enzymes, or consistent imaging results. However, sensitivity and specificity can vary depending on the population and cut-off values used. This study evaluated the suitability of amylase and lipase as first-line diagnostic biomarkers of suspected AP for the local population served by Tygerberg Hospital, South Africa. This retrospective analysis was conducted in June 2019 using all amylase and/or lipase request data from December 2018. Patient clinical data were included in sensitivity and specificity analyses of amylase, lipase or dual requests for diagnosis of AP. Cost per test data were obtained from the National Health Laboratory Service and used to calculate the total cost of the tests and potential savings. Sensitivity for lipase was 90.0% compared to 50.0% for amylase. Specificity was similar for singular measurements of lipase and amylase. Dual measurement of amylase and lipase showed no improvement in sensitivity (83.3%) and only a minor increase in specificity (97.4%) compared with measurement of lipase alone. The estimated savings was R2522.85 ($174.98 USD), with a potential annual cost saving of R84 423.74 ($5855.69 USD). Lipase was shown to be a more sensitive biomarker compared to amylase for the screening of AP, providing evidence for laboratories to educate local staff and promote improved requesting practices by clinicians. Additionally, preventing unnecessary dual requests may reduce costs.


New ruthenium(II) complexes functionalized with coumarin derivatives: synthesis, energy-transfer-based sensing of esterase, cytotoxicity, and imaging studies.
Two new bichromophoric ruthenium(II) complexes, [Ru(bpy)(2)(bpy-CM)](PF(6))(2) and [Ru(bpy)(2)(bpy-CM343)](PF(6))(2) (bpy=2,2'-bipyridine, CM=coumarin) with appended coumarin ligands have been designed and synthesized. The energy-transfer-based sensing of esterase by the complexes has been studied by using UV/Vis and luminescence spectroscopic methods. The cytotoxicity and the cellular uptake of one of the complexes have also been investigated.


Interaction mechanisms of peanut protein isolate and high methoxyl pectin with ultrasound treatment: The effect of ultrasound parameters, biopolymer ratio, and pH.
Ultrasound could effectively change molecular structure of proteins, polysaccharides, and their interactions, and was used to treat the peanut protein isolate-high methoxy pectin (PPI-HMP) complexes in this study. Effects of different ultrasound parameters, PPI-HMP mixing ratio (40:1-5:2), and pH (2.0-8.0) on the PPI-HMP interactions were investigated. Turbidity, solution appearance, and Zeta-potential analysis revealed an electrostatic interaction between PPI and HMP from pH 2.0 to pH 6.0. Ultrasound changed the tertiary structure conformation of PPI according to the surface hydrophobicity analysis. Increased ultrasound power density and pH broke the hydrogen bonds between the complexes according to Fourier transform infrared spectroscopy analysis. Apparent viscosity and confocal laser scanning microscopy analysis showed that appropriate ultrasound treatment (5.43 W/cm3, 25 min, 25 °C) reduced the viscosity of the complexes, and enhanced the electrostatic and hydrophobic interactions between PPI and HMP. These findings will contribute to the application of PPI-HMP complexes in the food industry.


Apoptosis propagates through the cytoplasm as trigger waves.
Apoptosis is an evolutionarily conserved form of programmed cell death critical for development and tissue homeostasis in animals. The apoptotic control network includes several positive feedback loops that may allow apoptosis to spread through the cytoplasm in self-regenerating trigger waves. We tested this possibility in cell-free Xenopus laevis egg extracts and observed apoptotic trigger waves with speeds of ~30 micrometers per minute. Fractionation and inhibitor studies implicated multiple feedback loops in generating the waves. Apoptotic oocytes and eggs exhibited surface waves with speeds of ~30 micrometers per minute, which were tightly correlated with caspase activation. Thus, apoptosis spreads through trigger waves in both extracts and intact cells. Our findings show how apoptosis can spread over large distances within a cell and emphasize the general importance of trigger waves in cell signaling.


Empathy in Healthcare Professionals during the Coronavirus Pandemic.
Empathy is important for successful interactions. The aim of the present study was to determine whether the cognitive component (Perspective taking) and affective components (Empathic concern and Personal distress) of empathy in health professionals were related to the degree of perceived threat of coronavirus, difficulties in doing work, difficulties in getting along with people, the health condition (current or past coronavirus disease), as well as with some socio-demographic characteristics. Fantasy as the cognitive component of empathy was not the focus of the present study as more irrelevant to clinical practice. A study of 296 health care workers through the Interpersonal Reactivity Index and a survey on perceived coronavirus threat, difficulties in work and getting along with people found that perceiving coronavirus as a stronger threat reduced both the cognitive component of empathy Perspective taking and the affective component of empathy Personal distress. As the affective components of empathy Empathic concern and Personal distress increased, the reported work difficulties were reduced. As the cognitive component of empathy Perspective taking and the affective component of empathy Personal distress increased, the reported difficulties in having a good relationship with other people were reduced. Some socio-demographic differences in the components of empathy in health workers were also established. These findings revealed the importance of Personal Distress (experienced anxiety, worry, discomfort, and apprehension when observing another person's negative experiences), as well as the joint manifestation of several aspects of empathy for successful work and maintaining good relationships in health care. Emotionality is a normal part of human interactions, so manifestations of cognitive empathy should not be only considered as appropriate, and emotional empathy should not be ruled out as unnecessary in clinical practice during the coronavirus pandemic.


A Simple Method of Generating 3D Brain Organoids Using Standard Laboratory Equipment.
3D brain organoids are a powerful tool with prospective application for the study of neural development and disease. Here we describe the growth factor-free method of generating cerebral organoids from feeder-dependent or feeder-free human pluripotent stem cells using standard laboratory equipment. The protocol outlined below allows generation of 3D tissues, which replicate human early in vivo brain development up to the end of the first trimester, both in terms of morphology and gene expression pattern.


[P323L Mutation in a Case with Prolonged SARS-CoV-2 PCR Positivity].
Coronavirus disease-2019 (COVID-19) emerged in the last months of 2019 and caused a pandemic effecting the whole world. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 has changed by various mutations since the day it was first identified, causing the pandemic to continue. Age, male gender, obesity, and comorbidity, which are general risk factors for COVID-19, can also cause prolonged PCR positivity. In this report, a case of 37-year-old male who is working in the hospital's COVID-19 molecular diagnostics laboratory was presented. He was vaccinated with three doses of inactivated vaccine, CoronaVac (Sinovac Biotech, Beijing-China), within the context of the vaccination program carried out in Türkiye. His first SARS-CoV-2 positivity was detected on 12.01.2021, four months after the last vaccination, and he continued to be detected positive for SARS-CoV-2 throughout a period of 39 days by quantitative reverse transcription polymerase chain reaction (qRT-PCR) tests performed with 2-3-day intervals. The patient has a 20-pack/year smoking history and his body mass index (BMI) was 29.8 kg/m2 at the time of his COVID-19. The case, which was clinically defined as mild COVID-19 with symptoms including back and headache, cough, fever (38.5°C), and loss of taste-smell, and without any additional complications or respiratory distress during the disease process. In the radiological examination, the lung was found within normal ranges. Prophylactic enoxaparin sodium anti-xa IU/0.6 ml was administered to the patient due to his cardiovascular risk, and no additional treatment was given. Whole genome sequencing was performed from nasopharyngeal swab samples of the patient at the beginning and 16th day of the infection to investigate the the specific genomic features and mutation pattern of the virus in the host over time, due to the prolonged SARS-CoV-2 PCR positivity. Library preparation for the whole next-generation sequencing (NGS) was performed by the SARS-CoV-2 Panel, Paragon CleanPlex kit (Paragon Genomics, USA), and indexing of the library was done by Clean-Plex Dual-Indexed PCR Primers for Illumina Set B kit (Paragon Genomics, USA). NGS analysis was performed on the Illumina Miniseq (Illumina, USA) platform. As a result of the bioinformatics evaluation, both samples were determined as SARS-CoV-2 Delta variant (Nextclade; 21J-Delta variant, Pango lineage; AY.43). Remarkably, the SARSCoV-2 sequences in the two samples taken 15 days apart; several identical mutations; such as D614G in the S gene, P323L in the ORF 1b gene region, and P1228L in the Nsp3 gene region, were detected. Besides that, when compared to the first sample, three additional mutations (P383L, P539S, L838I) were observed in the sequence of the second sample, which led to three amino acid changes, the clinical significance of which has not yet been determined in the literature. It is thought that; these mutations that change amino acid expression, as well as the other three mutations detected, may contribute to the improvement of the fitness of the virus and may be one of the factors responsible for the prolonged SARS-CoV-2 PCR positivity. Additional data to be obtained by further epidemiological sequencing studies will shed light on this issue.


Whole-genome bisulfite sequencing reveals the function of DNA methylation in the allotransplantation immunity of pearl oysters.
In the pearl culture industry, a major challenge is the overactive immunological response in pearl oysters resulting from allotransplantation, leading to shell-bead rejection and death. To better understand the molecular mechanisms of postoperative recovery and the regulatory role of DNA methylation in gene expression, we analyzed the changes in DNA methylation levels after allotransplantation in pearl oyster Pinctada fucata martensii, and elucidated the regulatory function of DNA methylation in promoter activity of nicotinic acetylcholine receptor (nAChR) gene. We constructed nine DNA methylomes at different time points after allotransplantation and used bisulfite genomic sequencing PCR technology (BSP) to verify the methylation status in the promoter of nAChR. We performed Dual luciferase assays to determine the effect of the dense methylation region in the promoter on transcriptional activity and used DNA pull-down and mass spectrometry analysis to assess the capability of transcription factor binding with the dense methylation region. The DNA methylomes reveal that CG-type methylation is predominant, with a trend opposite to non-CG-type methylation. Promoters, particularly CpG island-rich regions, were less frequently methylated than gene function elements. We identified 5,679 to 7,945 differentially methylated genes (DMGs) in the gene body, and 2,146 to 3,385 DMGs in the promoter at each time point compared to the pre-grafting group. Gene ontology and pathway enrichment analyses showed that these DMGs were mainly associated with "cellular process", "Membrane", "Epstein-Barr virus infection", "Notch signaling pathway", "Fanconi anemia pathway", and "Nucleotide excision repair". Our study also found that the DNA methylation patterns of the promoter region of nAChR gene were consistent with the DNA methylomics data. We further demonstrated that the dense methylation region in the promoter of nAChR affects transcriptional activity, and that the methylation status in the promoter modulates the binding of different transcription factors, particularly transcriptional repressors. These findings enhance our understanding of the immune response and regulation mechanism induced by DNA methylation in pearl oysters after allotransplantation.


Modality comparison for small animal radiotherapy: a simulation study.
Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. This paper presents a comparison of dose distributions generated by the three approaches-a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.


Evaluation of physical health effects due to volcanic hazards: the use of experimental systems to estimate the pulmonary toxicity of volcanic ash.
Shortly after Mount St. Helens erupted in 1980, a number of laboratories began to investigate the effects of volcanic ash in a variety of experimental systems in attempts to predict effects that might occult in the lungs of humans exposed to volcanic ash. The published results are remarkably consistent, despite the use of non-uniform ash samples and variability in the experimental approaches used. The data indicate that volcanic ash, even in high concentrations, causes little toxicity to lung cells in vitro and in vivo, as compared with effects of free crystalline silica, which is known to be highly fibrogenic. Volcanic ash does not appear to be entirely inert, however, possibly because of low concentrations of free crystalline silica in the ash. The published experimental studies suggest that inhaled volcanic ash is not likely to be harmful to the lungs of healthy humans, but the potential effects of volcanic ash in patients with pre-existing lung diseases are more difficult to ascertain from these studies.


[Studies on the anticancer effects of total alkaloid from Viscum coloratum].
To study the anticancer effects of total alkaloid from Viscum coloratum in vivo and vitro. In vitro, MTT assays were used t o measure the inhibitory effect. Cells at period of logarithmic growth were incubated for 24 hours. Then total alkaloid of various concentrations were added. 24 hours later, supernatant was removed and MTT was added. 4 hours after that, DMSO was added, then 30 minutes later, A value was measured. In vivo, suspension of carcinoma cells was implanted in the mice's limbs subcutaneously, 0.2mL each. 24 hours later, the mice were grouped randomly. Fed by total alkaloid continuously for 7 days, the mice were sacrificed. The tumors were weighed and calculated the inhibitory rates. In vitro, it shows that total alkaloid has prominent inhibitory effect on the growth of carcinoma cells. In vivo, it shows that total alkaloid can inhibit the growth of tumors and prolong the survival days of the mice bearing tumors. Total alkaloid from Viscum coloratum has the activities of anticancer.


Unique contributions of specific neuropsychiatric symptoms to caregiver burden in informal caregivers family members of patients with dementia.
We aimed to evaluate how the presence of individual neuropsychiatric symptoms in non-institutionalised patients with dementia is associated with caregiver burden of their informal caregivers, family members. We performed a cross-sectional study on a total of 131 pairs of one informal caregiver family member and non-institutionalised patient with dementia in a family medicine practices in a city of Zagreb, Croatia. Caregiver measures included Zarit Burden Interview (ZBI) whereas patient measures included Mini mental state examination (MMSE), Barthel index and Neuropsychiatric Inventory Questionnaire (NPI-Q). Total NPI-Q score explained 21% of overall burden. In order of strength of the association, after adjustments for age, sex, MMSE and Barthel index, overall burden was significantly associated with higher NPI-Q scores for agitation/aggression, apathy/indifference, irritability/lability, disinhibition, motor disturbance, appetite/eating, depression/dysphoria, anxiety, elation/euphoria and nighttime behaviours. When evaluating mutually independent contribution of unique NPI-Q symptoms to caregiver burden, agitation/aggression and apathy/indifference remained only two mutually independently associated symptoms, each explaining 5% of overall burden in this context. Informal caregivers who provide for family members with dementia suffering from agitation/aggression or apathy/indifference should be recognised as under special risk for the development of caregiver burden and considered as candidates for early targeted interventions.


The outcome of expectant management of congenital cystic adenomatoid malformations (CCAM) of the lung.
The appropriate management of asymptomatic congenital cystic adenomatoid malformations of the lung (CCAM) remains controversial. The aim of this study is to determine the outcome of expectant management of these lesions and the sensitivity of antenatal ultrasound diagnosis. A retrospective review was undertaken of all cases identified from prospectively collected databases with an antenatal or postnatal diagnosis of CCAM in the Northern region of England between 1985 and 2006 where such lesions underwent resection only when symptomatic. Thirty-seven cases of confirmed CCAM were identified antenatally or postnatally. Twenty-six (70%) were identified by antenatal ultrasound scans (during a period of near-universal antenatal scanning), of whom 21 (81%) were liveborn. In total, 16 of 29 (55%) liveborn infants with CCAM were symptomatic, and either died within the first postnatal week or underwent resection. Thirteen (45% of livebirths) were managed expectantly and remained asymptomatic. The sensitivity of antenatal ultrasound screening for CCAM increased over the period to 90% in the latter half of the study (p=0.035), although the positive predictive value (66%) did not improve. Expectant management was a reasonable option for almost half of the babies, but over one third required surgery for CCAM, most becoming symptomatic in infancy. In view of the uncertainty that surrounds decisions regarding expectant or pre-emptive resection in asymptomatic infants, the authors advocate having an open and honest discussion when counselling parents (particularly antenatally) regarding surveillance or expectant management as a reasonable strategy.


Respiratory responses to passive and active recovery from exercise.
To investigate the effect of the neural components associated with leg movements on the control of ventilation during recovery from exercise, we recorded the minute ventilation (VE), oxygen uptake (VO2), and carbon dioxide output (VCO2) of eight normal volunteers during recovery from moderate, steady-state cycle exercise (170 W). The recovery phases were undergone separately under two different conditions: 5 min of rest (passive recovery) on a bicycle ergometer and 3 min of pedaling at a work rate of 0W (active recovery) followed by 2 min of rest. The phase-1 responses were observed in all the variables studied at the transition of passive recovery but not in the active recovery phase. The kinetics of VCO2, during the off-transition were significantly faster than those of VE in both recoveries, indicating that the decreases in VCO2 could precede the decreases in VE. Although the levels of VE and VCO2 during active recovery were significantly higher than those during passive recovery, the decline in VE was closely proportional to that of VCO2 under both recovery conditions, with resultant indications of similar VE-VCO2 regression lines. These findings suggest that the flux of CO2 to the lungs is an important determinant of ventilatory drive during recovery, and that neither central command nor neural afferents from contracting muscles are requisite for the control of ventilation during recovery from exercise.


A Rare and Interesting Presentation of Diabetic Ketoacidosis Caused by Native Aortic Valve Endocarditis Complicated by Aortic Root Abscess Resulting in Multiple Septic Emboli Causing Bowel Ischemia and Splenic Infarction.
Diabetic ketoacidosis (DKA) is a serious life-threatening complication of diabetes, often precipitated by infection. Infective endocarditis (IE) is a serious precipitating factor for DKA, especially in patients with a previous cardiac surgery or valvular pathology. IE can be further complicated by life-threatening embolic events, which could be fatal if not detected and managed early and effectively. Our patient is a 54-year-old diabetic who presented with DKA precipitated by native aortic valve endocarditis complicated by an aortic root abscess, which was further complicated by septic emboli to the splenic artery and superior mesenteric artery leading to splenic infarction and bowel ischemia, respectively. To our knowledge and as per the literature reviewed, no case has been reported in a single patient who presented with DKA precipitated by IE complicated by aortic root abscess and multiple septic emboli resulting in bowel ischemia and splenic infarction.


Kirschner wire migration from the right sternoclavicular joint to the heart: a case report.
Presented here is a rare case in which Kirschner wires migrated from the right sternoclavicular joint to the heart. A 29-year-old man suffering from sternoclavicular instability due to a motorcycle accident received surgical fixation with Kirschner wires. Six months after the surgery, the chest x-ray showed migration of the 3 broken wires to the anterior mediastinum and to the right hemithorax. The patient was asymptomatic and was scheduled for elective surgical extraction of the migrating wires because of the potential danger of injuring the mediastinal organs.During the surgery, the intracardiac location of all wires was discovered,and the wires were successfully extracted from the extracorporeal circulation. This rare and potentially lethal complication is discussed.


The effects of age to meet the standard production rate.
This study evaluated the energy expenditure of workers in physical work tasks in order to determine if people of different ages and gender carry out repetitive activities according to the recommended limits of energy at work. Exploring whether age is a significant factor to achieve industrial production rates and determine its possible consequences. A laboratory experiment was conducted with people age 20 to 58 years split by gender into four age groups. Oxygen consumption and heart rate were measured as variables of response to the physical workloads. When carrying out repetitive moderate load operations, women aged over 30 years exceeded the recommended energy expenditure (95% CI). For heavy activities, only men in the age groups 20-39 and 30-40 years could perform these tasks without exceeding the recommended oxygen consumption (95% CI). The industrial predetermined motion time systems do not take into account the effects of age and gender difference on energy production when obtaining cycle times in activities with significant aerobic loads. Manufacturing processes have specific standard times that might be inappropriate if they are performed by individuals who do not meet the standard energy production capacity.


Perceived physical activity during stay-at-home COVID-19 pandemic lockdown March-April 2020 in Polish adults.
Lockdowns amid the COVID-19 pandemic drastically reduced the possibility of undertaking physical activity (PA) in gyms, swimming pools, or work-related PA, e.g., active commuting. However, the stay-at-home order could have reduced PA the most, i.e., the ban of unnecessary outdoor activities. It affected free walking, running, skiing, active tourism, etc. It is, therefore, crucial to estimate how the stay-at-home order affected PA. We estimated how the stay-at-home order affected perceived PA and sedentary behavior compared to the pre-pandemic time in Poland. We used a self-reported International Physical Activity Questionnaire-Long Form (IPAQ-LF) to estimate the time (minutes per day) of vigorous and moderate PA and walking and sitting time. We gathered data from 320 Polish participants. Bayesian approaches, including t-test and Bayesian correlations, were used to find differences and correlations between PA before and during the stay-at-home lockdown. Our data supported the hypotheses that vigorous PA, as well as walking, declined during the lockdown. Surprisingly, our data did not support the hypothesis that moderate physical activity was reduced. We found that moderate PA during lockdown increased compared to the pre-lockdown PA. As hypothesized, our data strongly evinced that sitting time inclined during the lockdown. PA decline was not correlated with the available living space. People who had access to gardens did not demonstrate a higher PA level than those without. Walking and sitting time have drastically changed during the stay-at-home lockdown, decreasing and increasing, respectively. Given results from studies focusing on lockdowns without the stay-at-home restriction, it may be assumed that letting people go outside is crucial in keeping them more active and less sedentary. Authorities should take into account the effect the stay-at-home order may have on PA and sedentary behavior and as a result, on health. Stay-at-home orders should be the last considered restriction, given its detrimental consequences.


Transcriptomic Analysis Reveals Fibroblast Growth Factor 11 (FGF11) Role in Brown Adipocytes in Thermogenic Regulation of Goats.
Brown adipose tissue (BAT) is the main site of adaptive thermogenesis, generates heat to maintain body temperature upon cold exposure, and protects against obesity by promoting energy expenditure. RNA-seq analysis revealed that FGF11 is enriched in BAT. However, the functions and regulatory mechanisms of FGF11 in BAT thermogenesis are still limited. In this study, we found that FGF11 was significantly enriched in goat BAT compared with white adipose tissue (WAT). Gain- and loss-of-function experiments revealed that FGF11 promoted differentiation and thermogenesis in brown adipocytes. However, FGF11 had no effect on white adipocyte differentiation. Furthermore, FGF11 promoted the expression of the UCP1 protein and an EBF2 element was responsible for UCP1 promoter activity. Additionally, FGF11 induced UCP1 gene expression through promoting EBF2 binding to the UCP1 promoter. These results revealed that FGF11 promotes differentiation and thermogenesis in brown adipocytes but not in white adipocytes of goats. These findings provide evidence for FGF11 and transcription factor regulatory functions in controlling brown adipose thermogenesis of goats.


Recurrent meningitis with upper airway obstruction in a child: frontonasal encephalocele- a case report.
Nasal encephalocele are rare congenital anomalies; these benign masses may be confused with nasal dermoids, hemangiomas, nasal gliomas and anterior skull base masses. These lesions have concomitant defects in the anterior cranial fossa thus this potential communication can cause recurrent episodes of meningitis and/or difficulty in breathing and cosmetic anomalies. We bring a case of a 6-year-old child who presented to the clinic with multiple episodes of meningitis which was associated with nasal discharge. The imaging studies and nasal fluid analysis confirmed it as cerebrospinal fluid; subsequently imaging findings concluded it as frontonasal encephalocele which was later resected and patient showed improvement.


Anticomplement immunofluorescence for the titration of antibody to varicella-zoster virus.
Anticomplement immunofluorescence (ACIF) was tested for its use for the titration of antibody against varicella-zoster virus (VZV). ACIF antibody responses of patients with VZV infection were specific for VZV antigen and heterotypic responses to herpes simplex virus type-1 and cytomegalovirus antigens were not observed. Comparative studies of ACIF, membrane immunofluorescence (MIF) and indirect immunofluorescence (IF), using acetone-fixed antigen, were carried out with nonimmune sera and convalescent sera of patients who had recovered from varicella, herpes zoster and Rumsey Hunt disease. Nonspecific staining occurred with some nonimmune sera at a 1:4 dilution in the MIF and IF tests, after freezing and thawing of the serum, but not in the ACIF test. The antibody titers in convalescent sera agreed well in these three methods and the highest titer was obtained by MIF. The titers in ACIF and IF were similar but the ACIF antibody decreased earlier than the IF antibody during convalescence. On the other hand there was a discrepancy between the titers of ACIF and those of MIF and IF antibody in the sera of healthy adults, all sera with titers higher than 10 in the MIF and IF tests had titers below 10 in the ACIF test. The average titer of ACIF antibody declined to less than 10 with increasing age (13 to more than 20 years), whereas the MIF antibody increased during the same period of life.


Integrating carbonyl iron with sponge to enable lightweight and dual-frequency absorption.
In this work, sponge impregnated with iron pentacarbonyl was utilized to obtain a novel composite in which the carbonyl iron (CI) was embedded in a graphitized carbon matrix (CI-C). The CI that results from the thermal pyrolysis of iron pentacarbonyl can homogeneously disperse into the pore structures of the sponge skeleton, which not only improves the stability of the CI, but also modifies the impedance matching character. Moreover, the sponge bulk turns into graphitized carbon during the heat treatment (graphitized catalysis of magnetic metal on carbon at high temperature). Due to the respective strong dissipation ability of CI and the graphitized carbon matrix, the as-prepared CI-C sample exhibits a good microwave absorption performance, including expanding the effective absorption bandwidth and reduced weight, compared to pure CI. Moreover, the sample with 30 wt% paraffin loading not only shows strong reflection loss absorbing ability, but also possesses continuous dual-absorption peaks (9.96 GHz, -38.7 dB, and 13.8 GHz is -37.6 dB). This work not only extends the application of carbonyl iron as a lightweight microwave absorber with dual-absorption peaks but also initiates a new approach for artificially designed carbon-based composites via a simple sponge-impregnation method.


[Surgical treatment of gastric carcinoma in the elderly. Clinical considerations on a group of patients undergoing major surgical destruction].
A group of 24 patients in senile age was subjected to major demolition operations, for purposes of radical removal of gastric carcinoma (total gastrectomy, subtotal resection, oesophago-gastric resection). In six patients the major operation was widened by partial demolition of neighbouring organs (liver, colon, pancreas). The flattering results (both immediate and long-term) obtained from this operation and the progress reached in the knowledge and correction of the senile physiopathological alterations allow encouraging developments to be forecast for this surgery, the success of which is subject to careful tactical selections and to close multidisciplinary cooperation directed to strengthening vital reserves, assistance of main functions and prompt recognitions and treatment of any complications.


Activation of MAP kinases by green leaf volatiles in grasses.
Previously we have shown that mechanical wounding and volatiles released from cut grass, activated a 46 and 44 kDa mitogen-activated protein kinase (MAPK) in the model grass species Lolium temulentum (Lt). MAPKs play an important role as signal relays that connect incoming stress signals and stress responses. Since green leaf volatiles (GLV) are released during wounding, we wanted determine if specific compounds contained in the GLV mixture or if GLV generated from other plant species could activate these Lt MAPKs. Our analysis found that just a 1-min exposure to GLV was enough to activate the Lt 46 kDa MAPK within 3 min and the 44 kDa MAPK within 15 min. This activation pattern showed similar kinetics to those observed after wounding, and the GLV and wound activated bands associated with these MAPKs displayed identical migration on sodium dodecyl sulfate polyacrylamide gels. Thirteen different commercially available plant volatiles (alcohols, aldehydes and ketones) were tested and all thirteen volatile compounds were able to activate these same Lt MAPKs. Furthermore, GLV derived from three other grass species as well as tomato, a dicot, were also shown to activate these MAPKs in Lt.


Choriocarcinoma-associated pulmonary thromboembolism and pulmonary hypertension: a case report.
Cases of pulmonary embolism and pulmonary artery hypertension caused by choriocarcinoma represent a rare clinical emergency. We report a case of a 25-year-old woman who presented with pulmonary embolism and hypertension and died soon after complete pulmonary embolectomy. A related literature review revealed that almost all of these patients had previously experienced a spontaneous abortion (average, 6 months) and were not pregnant.


Feasibility of tongue strength measurements during (chemo)radiotherapy in head and neck cancer patients.
The aim of this study was to investigate the feasibility of tongue strength measures (TSMs) and the influence of bulb location, sex, and self-perceived pain and mucositis in head and neck cancer (HNC) patients during chemoradiotherapy (CRT). Twenty-six newly diagnosed HNC patients treated with CRT performed anterior and posterior maximal isometric tongue pressures by means of the Iowa Oral Performance Instrument (IOPI). The Oral Mucositis Weekly Questionnaire (OMWQ) and a Visual Analogue Scale (VAS) for pain during swallowing were completed weekly from baseline to 1 week post CRT. Feasibility of TSMs during CRT declines significantly from 96 to 100% at baseline to 46% after 6 weeks of CRT. But post-hoc analyses reveal only significant differences in feasibility between baseline and measurements after 4 weeks of treatment. No effect of gender or bulb location was established, but feasibility is influenced by pain and mucositis. Feasibility of TSMs declines during CRT and is influenced by mucositis and pain. For the majority of subjects, TSMs were feasible within the first 4 weeks, which provides a window of scientific and clinical opportunities in this patient population.


Fast Electron Detachment Dissociation of Oligonucleotides in Electron-Nitrogen Plasma Stored in Magneto Radio-Frequency Ion Traps.
We report "plasma" electron detachment dissociation (EDD), a novel electron-activated dissociation (EAD) method for the fast sequencing of oligonucleotides with a high sequence coverage. To reduce the repulsive Coulombic force between the deprotonated oligonucleotides and the electron beam, we performed EDD in a neutral electron-nitrogen (N2+) plasma stored in a magneto radio-frequency ion trap. We confirmed that plasma EDD accomplished a high sequence coverage (100%) of RNA with 40 mers in the reaction time of 10 ms using the electron beam kinetic energy of 35 eV. This new technique was applied to various modifications in oligonucleotide therapeutics (ONTs). Phosphorothioate (PS) positions showed an extremely high dissociation efficiency, i.e., 100 times higher than the standard phosphate (PO) in DNA. Locked nucleotides did not show intensive dissociation in EDD; however, collision-induced dissociation (CID) helped sequence these portions. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a ZenoTOF mass spectrometer equipped with the plasma EDD technique successfully identified impurities in degraded samples.


Balloon Aortic Valvuloplasty in the Transcatheter Aortic Valve Implantation Era.
As the population continues to grow, and life expectancy has increased, aortic stenosis (AS) has become the most common valvular disease requiring surgical treatment. The evolution of valve replacement therapies has progressed significantly since 1960. In the last 20 years, transcatheter aortic valve implantation (TAVI) has been a game changer, and has potential to become the standard of care. Despite uncertain prognosis benefits, balloon aortic valvuloplasty (BAV) can be useful in a broad range of patients with AS, as well as being a bridging therapy to valve replacement, or as a destination therapy, besides its role in TAVI procedures. This review describes the contemporary role of BAV in AS treatment, and focuses on technical improvements that reframe BAV as an effective tool in a variety of clinical scenarios. One of these improvements is transradial BAV, either with the conventional approach of BAV or applying the bilateral technique with two balloons.


Construction of a Nomogram Model for Predicting Pleural Effusion Secondary to Severe Acute Pancreatitis.
This study aims to investigate the risk factors of pleural effusion (PE) secondary to severe acute pancreatitis (SAP) and to build a nomogram model. The clinical parameters of SAP patients admitted to the emergency department of the First Affiliated Hospital of Bengbu Medical College from January 2019 to August 2021 were retrospectively collected. The independence risk factors of PE secondary to SAP were analyzed by univariate analysis and multivariate logistic regression analysis. A nomogram risk prediction model was established and validated through the area under the ROC curve. Two hundred twenty-two SAP patients were included for analysis, of which 65 patients experienced secondary PE. The incidence of PE secondary to SAP was 29.28% (65/222). Logistic regression analysis showed that serum albumin (ALB) (OR = 0.830, 95% CI: 0.736∼0.936), fibrinogen (FIB) (OR = 4.573, 95% CI: 1.795∼11.648), C-reactive protein (CRP) (OR = 1.046, 95% CI: 1.009∼1.083), acute physiology, chronic health score system (APACHE-II) score (OR = 1.484, 95% CI: 1.106∼1.990), and sequential organ failure score (SOFA) (OR = 43.038, 95% CI: 2.030∼4.548) were independent risk factors for PE secondary to SAP (P < 0.05) and entered into the nomogram. The nomogram showed robust discrimination with an index of concordance of 0.755 and an area under the receiver operating characteristic curve of 0.837 (95% CI: 0.779∼0.894). We developed a nomogram model for PE secondary to SAP with ALB, FIB, CRP, APACHE-II scores, and SOFA scores. The nomogram model showed good discrimination and consistency, and it can better predict the risk of PE secondary to SAP.


Evidence for regulation of reinitiation in translational control of GCN4 mRNA.
Translational control of the GCN4 gene of Saccharomyces cerevisiae is mediated by four upstream open reading frames (URFs) present in the leader of GCN4 mRNA. URFs 3 and 4 efficiently repress GCN4 expression in normal growth conditions; URFs 1 and 2 are required to overcome this repression in amino acid-starved cells. lacZ fusions to URFs 3 and 4 were used to determine the translational event that is regulated at these sequences by URFs 1 and 2. URF3-lacZ, URF4-lacZ, and GCN4-lacZ fusions are affected similarly by URFs 1 and 2 when no other URFs are present in the leader: expression from all three fusions is reduced by an amount slightly greater in repressing than in derepressing conditions. These results are inconsistent with models that postulate a differential effect of URFs 1 and 2 on initiation or elongation rates at URFs 3 and 4 versus the GCN4 coding sequences. We propose that the efficiency of reinitiation at the GCN4 AUG codon after translation of URFs 3 and 4 is the translational event that is stimulated in derepressing conditions by URFs 1 and 2.


'Talk to me' patient communication in a long-term care facility.
1. Staff are important facilitators for communication among elderly patients, who often are alone and bored for long periods. 2. Staff serve as an essential link between the patients and the outside world, and serve as a conduit for initiating contact between residents. 3. Environment--including the selection of roommates, the proximity of residents, and the volume of radios and televisions--may greatly alter residents' ability to communicate.


Prolonged hypothyroidism severely reduces ovarian follicular reserve in adult rats.
There is substantial evidence both in humans and in animals that a prolonged reduction in plasma thyroid hormone concentration leads to reproductive problems, including disturbed folliculogenesis, impaired ovulation and fertilization rates, miscarriage and pregnancy complications. The objective of the present study is to examine the consequences of chronic hypothyroidism, induced in adulthood, for the size of the ovarian follicle pool. In order to investigate this, adult female rats were provided either a control or an iodide deficient diet in combination with perchlorate supplementation to inhibit iodide uptake by the thyroid. Sixteen weeks later animals were sacrificed. Blood was collected for hormone analyses and ovaries were evaluated histologically. At the time of sacrifice, plasma thyroid-stimulating hormone concentrations were 20- to 40-fold increased, thyroxine concentrations were negligible while tri-iothyronin concentrations were decreased by 40% in the hypothyroid group, confirming that the animals were hypothyroid. Primordial, primary and preantral follicle numbers were significantly lower in the hypothyroid ovaries compared to the euthyroid controls, while a downward trend in antral follicle and corpora lutea numbers was observed. Surprisingly the percentage of atretic follicles was not significantly different between the two groups, suggesting that the reduced preantral and antral follicle numbers were presumably not the consequence of increased degeneration of these follicle types in the hypothyroid group. Plasma anti-Müllerian hormone (AMH) levels showed a significant correlation with the growing follicle population represented by the total ovarian number of primary, preantral and antral follicles, suggesting that also under hypothyroid conditions AMH can serve as a surrogate marker to assess the growing ovarian follicle population. The induction of a chronic hypothyroid condition in adult female rats negatively affects the ovarian follicular reserve and the size of the growing follicle population, which may impact fertility.


Draft Genome Sequence of Taylorella equigenitalis Strain ERC_G2224 Isolated from the Semen of a Lipizzaner Stallion in South Africa.
Taylorella equigenitalis is the causative agent of contagious equine metritis (CEM), a sexually transmitted infection of horses. We report here the genome sequence of T. equigenitalis strain ERC_G2224, isolated in 2015 from a semen sample collected in 1996 from a Lipizzaner stallion in South Africa.


The influence of cyclobarbital and diazepam on drug metabolism in vitro and their binding to cytochrome P-450.
Cyclobarbital inhibited diazepam metabolism by rat liver supernatant only at concentrations of 1 mM. Ethylmorphine N-demethylation is strongly inhibited by diazepam in a non-competitive manner whereas cyclobarbital shows a competitive inhibition type. Both cyclobarbital and oxazepam are weak inhibitors. Hexobarbital- evokes typical type I spectral changes with rat liver microsomes whereas cyclobarbital and diazepam-induced spectral changes are similar to type II or inverse type I. Barbital evoked the same type of spectral changes as diazepam and cyclobarbital. With the usual concentration in vivo the metabolism of diazepam and other drugs can scarcely be influenced by cyclobarbital.


Converging evidence implicates the abnormal microRNA system in schizophrenia.
Previous findings are inconsistent; yet, converging evidence suggests an association between schizophrenia (SZ) and the impairment of posttranscriptional regulation of brain development through microRNA (miRNA) systems. This study aims to (1) compare the overall frequency of 121 rare variants (RVs) in 59 genes associated with the miRNA system in genome-wide association studies (GWAS)-derived data including 768 SZ cases and 1348 healthy controls and validated in an independent GWAS data including 1802 SZ cases and 1447 controls; (2) profile genome-wide miRNA expression in blood collected from 15 early-onset SZ (EOS) cases and 15 healthy controls; and (3) construct a miRNA-messenger RNA (mRNA) regulatory network using our previous genome-wide mRNA expression data generated from a separate sample of 18 EOS cases and 12 healthy controls. Our findings indicate that: (1) In genes associated with the control of miRNAs, there are approximately 50% more RVs in SZ cases than in controls (P ≤ 2.62E-10); (2) The observed lower miRNA activity in EOS patients compared with the healthy controls suggests that miRNAs are abnormally downregulated; (3) There exists a predicted regulatory network among some downregulated miRNAs and some upregulated mRNAs. Collectively, results from all 3 lines of evidence, suggest that the genetically based dysregulation of miRNA systems undermines miRNAs' inhibitory effects, resulting in the abnormal upregulation of genome transcription in the development of SZ.


Vascular expression of the grp1.8 promoter is controlled by three specific regulatory elements and one unspecific activating sequence.
The bean grp1.8 full-length promoter is specifically active in vascular tissue during normal development of tobacco. Deletion of a negative regulatory element resulted in ectopic activity of the promoter in cortical cells of hypocotyls, roots and stems. A 169 bp fragment (-205 to -36) of the grp1.8 promoter conferred vascular-specific expression to CaMV 35S minimal promoters whereas a 141 bp fragment (-205 to -64) strongly activated these minimal promoters both in vascular and cortical cells. These experiments defined a new regulatory element (VSE) that is essential for vascular-specific expression and is located between -64 and -36. The 141 bp grp1.8 promoter sequence had enhancer-like properties as it was active in both orientations. A 24 bp sequence (bp -119 to -96, corresponding to the SE1 regulatory element) enhanced expression from several minimal promoters strongly but unspecifically, whereas a 26 bp sequence (-98 to -73, corresponding to the RSE regulatory element) induced vascular-specific expression. Thus, the grp1.8 promoter is regulated by a combinatorial mechanism that can integrate the action of different, non-additively acting regulatory elements into vascular-specific expression.


Pathologic analysis of chemical nephritis in rats induced by N-(3,5-dichlorophenyl)succinimide.
The effects of N-(3,5-dichlorophenyl)succinimide (NDPS) administration to rats were studied by blood chemical, histopathologic, histochemical, and ultrastructural examinations. Administration of 5000 p.p.m. of NDPS induced severe damage of the kidneys, but did not affect other organs. Administration of 2500 p.p.m. of NDPS had little effect, even on the kidneys. Chemical analysis of the blood showed that the urea nitrogen level increased with the increase in the period of NDPS administration. Histopathologic examination showed intensive cell infiltration, mainly of lymphocytes, into the renal interstitium after NDPS administration for only 4 weeks. After NDPS administration for 12 weeks or more, typical interstitial nephritis was observed. Histochemical analysis showed that after only 1 week various enzymatic activities in the proximal convoluted tubules were markedly decreased whereas their activities in the distal convoluted tubules were relatively well preserved for at least 4 weeks. These results indicate that NDPS predominantly attacked the proximal convoluted tubules. After 4 weeks, the most prominent ultrastructural changes were seen in the proximal convoluted tubules where the epithelial cells lost their polarity and had a very abnormal arrangement. These cells showed well developed, edematous microvilli, poorly developed basal infoldings, swollen mitochondria of various sizes, aggregated beta-type glycogen granules, and debris of erythrocytes. Development of the endoplasmic reticulum, Golgi complex, ribosomes, and lysosomes was poor in the cytoplasm. These investigations indicate that NDPS affects the function of the proximal convoluted tubules. NDPS is a selective nephrotoxic substance. That is, it initially damages the proximal convoluted tubules, and subsequently causes interstitial nephritis. It is suggested that nephritis induced by NDPS is useful as a model of interstitial nephritis in man.


Factors affects the performance of red crescent paramedics, Bisha, Saudi Arabia.
Saving lives is the ultimate purpose of the Red Crescent paramedics. It is crucial to enable safe, effective, and efficient performance of paramedics globally. In Saudi Arabia, the Red Crescent faces at least over 280,000 cases every year. Therefore, this study aims to address the factors affecting the performance of the Red Crescent paramedics. Descriptive qualitative study and all data processed were analyzed using thematic analysis. In total, 31 paramedic staff in Bisha city were invited to participate in this descriptive qualitative study. Among them, 11 paramedics agreed to participate in an in-depth semi-structured interview. The findings of the research indicated three themes. The first theme was a lack of awareness in society, with three sub-themes: types of emergency calls, the crowd that gathers at the incident location, and people interruptions. Theme 2 was the long distance and road obstacles, and other factors that affect the paramedics were the third theme. Policymakers and the community should obtain a clear understanding of the Red Crescent paramedic interventions to help to create policies, legislation, and guidelines suitable for the needs of paramedics.


Expression and function of toll-like receptors in human circulating endothelial colony forming cells.
Mature endothelial cells are known to sense microbial products through toll-like receptors (TLRs), a family of membrane proteins which serve as pathogen recognition and signaling elements; however, there are limited data in the literature about the expression and function of TLRs in human circulating endothelial colony forming cells (ECFCs), which are considered the most likely endothelial precursors. We expanded and differentiated in vitro umbilical cord blood (UCB) and adult peripheral blood (PB) ECFCs and studied the expression of TLR1 to TLR10 mRNA by qPCR analysis, and we further characterized TLR function in ECFCs through functional assays including in vitro ECFC growth and differentiation, assessment of cytokine production, and measurement of intracellular Ca(2+) signals. Both UCB- and PB-ECFCs had detectable mRNA levels of all the TLRs from 1 to 10; TLR4, a sensor of Gram-negative bacterial lipopolysaccharide (LPS), had a higher level compared to other TLRs. Exposure to LPS induced cytokine production, although with less efficiency compared to PB-mononuclear cells. However, no effect of LPS was seen on ECFC growth and differentiation, and no increase in intracellular Ca(2+) concentrations, which is essential for ECFC proliferation, was observed after exposure to increasing amounts of LPS. Our data show that all TLRs from 1 to 10 are constitutively expressed in ECFCs, and suggest that TLR4 is functional in ECFCs, but its activation through its ligand LPS does not affect ECFC growth and differentiation.


Housing Conditions and Health Implications for Migrant Agricultural Workers in Canada: A Scoping Review.
Migrant agricultural workers face various health inequities that have led to preventable illness and death. This paper investigates how material housing conditions have shaped physical and mental health outcomes for temporary foreign workers in Canadian agriculture. We conducted a scoping review of literature on migrant agricultural worker housing in Canada published between 2000-2022, analysing insights on the physical quality of workers' housing in relation to international frameworks on housing quality. Our review revealed a range of housing-related health risks, including: (1) Sanitation, food security, and water; (2) Thermal safety, electricity, and utilities; (3) Habitability of structure, air quality, and exposure to hazards; (4) Spacing, privacy, and co-worker relations and; (5) Geographic proximity to necessary services and social opportunities. Although housing has been increasingly recognized as a social determinant of health, little research examines how migrant farmworkers' accommodations shape their health outcomes, particularly in Canada. This scoping review provides timely insights and recommendations to inform research, policy, and public health interventions.


Plant specimen contextual data consensus.
The Compliance and Interoperability Working Group of the Genomic Standards Consortium facilitates the establishment of a community of experts and the development of recommendations to describe genomic data and associated information. Here we present our ongoing conation to harmonise the reporting of contextual plant specimen data associated with genomics and functional genomics. This commentary summarises the current state of our plant sample contextual data harmonisation efforts to engage a broad plant science community.


Endoplasmic reticulum stress-induced degradation of DNAJB12 stimulates BOK accumulation and primes cancer cells for apoptosis.
DNAJB12 (JB12) is an endoplasmic reticulum (ER)-associated Hsp40 family protein that recruits Hsp70 to the ER surface to coordinate the function of ER-associated and cytosolic chaperone systems in protein quality control. Hsp70 is stress-inducible, but paradoxically, we report here that JB12 was degraded by the proteasome during severe ER stress. Destabilized JB12 was degraded by ER-associated degradation complexes that contained HERP, Sel1L, and gp78. JB12 was the only ER-associated chaperone that was destabilized by reductive stress. JB12 knockdown by siRNA led to the induction of caspase processing but not the unfolded protein response. ER stress-induced apoptosis is regulated by the highly labile and ER-associated BCL-2 family member BOK, which is controlled at the level of protein stability by ER-associated degradation components. We found that JB12 was required in human hepatoma cell line 7 (Huh-7) liver cancer cells to maintain BOK at low levels, and BOK was detected in complexes with JB12 and gp78. Depletion of JB12 during reductive stress or by shRNA from Huh-7 cells was associated with accumulation of BOK and activation of Caspase 3, 7, and 9. The absence of JB12 sensitized Huh-7 to death caused by proteotoxic agents and the proapoptotic chemotherapeutic LCL-161. In summary, JB12 is a stress-sensitive Hsp40 whose degradation during severe ER stress provides a mechanism to promote BOK accumulation and induction of apoptosis.


Inhibition of glial hemichannels by boldine treatment reduces neuronal suffering in a murine model of Alzheimer's disease.
The contribution of reactive gliosis to the pathological phenotype of Alzheimer's disease (AD) opened the way for therapeutic strategies targeting glial cells instead of neurons. In such context, connexin hemichannels were proposed recently as potential targets since neuronal suffering is alleviated when connexin expression is genetically suppressed in astrocytes of a murine model of AD. Here, we show that boldine, an alkaloid from the boldo tree, inhibited hemichannel activity in astrocytes and microglia without affecting gap junctional communication in culture and acute hippocampal slices. Long-term oral administration of boldine in AD mice prevented the increase in glial hemichannel activity, astrocytic Ca2+ signal, ATP and glutamate release and alleviated hippocampal neuronal suffering. These findings highlight the important pathological role of hemichannels in AD mice. The neuroprotective effect of boldine treatment might provide the basis for future pharmacological strategies that target glial hemichannels to reduce neuronal damage in neurodegenerative diseases.


Cooperation between neurovascular dysfunction and Aβ in Alzheimer's disease.
The amyloid-β (Aβ) hypothesis was once believed to represent the pathogenic process of Alzheimer's disease (AD). However, with the failure of clinical drug development and the increasing understanding of the disease, the Aβ hypothesis has been challenged. Numerous recent investigations have demonstrated that the vascular system plays a significant role in the course of AD, with vascular damage occurring prior to the deposition of Aβ and neurofibrillary tangles (NFTs). The question of how Aβ relates to neurovascular function and which is the trigger for AD has recently come into sharp focus. In this review, we outline the various vascular dysfunctions associated with AD, including changes in vascular hemodynamics, vascular cell function, vascular coverage, and blood-brain barrier (BBB) permeability. We reviewed the most recent findings about the complicated Aβ-neurovascular unit (NVU) interaction and highlighted its vital importance to understanding disease pathophysiology. Vascular defects may lead to Aβ deposition, neurotoxicity, glial cell activation, and metabolic dysfunction; In contrast, Aβ and oxidative stress can aggravate vascular damage, forming a vicious cycle loop.


Restoration of Retarded Influenza Virus-specific Immunoglobulin Class Switch in Aged Mice.
The declined immune response to infection causes significant higher morbidity and mortality in aging in spite of the coexisted hyperimmunoglobulinemia (HIG). This study is to reveal the cellular basis of HIG and mechanism of weakened HA-specific IgG response in aged mice and to test cell therapy in the treatment of age-related IgG antibody production deficiency with immunocyte adoptive transfer. BALB/c mice was immunized with Influenza A/Taiwan vaccine and challenged with the same strain of virus. ELISA was used to assess the levels of total immunoglobulins and antigen specific antibody response. The flow cytometry and ELISPOT were used to evaluate the frequencies of total immunoglobulin- and specific antibody-producing and secreting B lymphocytes. In vitro expanded mononuclear cells, CD4+ T lymphocytes and CD20+ B lymphocytes from old and young mice were adoptively transferred into influenza virus-challenged aged mice, and HA-specific IgG responses were observed. It is found that old mice exhibited higher levels of total serum IgG, IgM and IgA, higher frequencies of IgG+, IgM+ and IgA+ cells, and greater antigen-specific IgM and IgA responses to influenza infection, in comparison to young mice. However, influenza antigen- specific IgG and its subclass responses in old mice were significantly lower. The retarded specific IgG response could be attributed to an insufficiency of immunoglobulin class switch in aging. Correlation analysis indicated that HIG and deficient specific IgG production in aged mice could be independent to each other in their pathogenesis. Correction of deficient specific IgG production by adoptive transfer of in vitro expanded and unexpanded CD4+ cells from immunized young mice suggests the CD4+ cell dysfunction contributes to the insufficiency of immunoglobulin class switch in aged mice. The transfusion of in vitro expanded lymphocytes could be a potential effective therapy for the age-related immunodeficiency and could play a role in the infection prevention in aging.


Thought for food: imagined consumption reduces actual consumption.
The consumption of a food typically leads to a decrease in its subsequent intake through habituation--a decrease in one's responsiveness to the food and motivation to obtain it. We demonstrated that habituation to a food item can occur even when its consumption is merely imagined. Five experiments showed that people who repeatedly imagined eating a food (such as cheese) many times subsequently consumed less of the imagined food than did people who repeatedly imagined eating that food fewer times, imagined eating a different food (such as candy), or did not imagine eating a food. They did so because they desired to eat it less, not because they considered it less palatable. These results suggest that mental representation alone can engender habituation to a stimulus.


From policy to practice in the Affordable Care Act: Training center for New York State's health insurance programs.
The United States currently faces the large, logistical undertaking of enrolling millions of Americans into a complex Affordable Care Act (ACA) system within a short period of time. One way states have addressed this implementation challenge is through the development of consumer assistance programs. In these programs, health care professionals-known as "Assistors"-are trained in insurance enrollment services to help consumers navigate the complex application and plan selection process, with the ultimate goal of optimizing enrollment rates. Cicatelli Associates Inc. (CAI), a non-profit capacity building organization, has served as the Statewide Training Center for New York's Health Insurance Program Initiative since 2013, before the ACA Marketplace roll-out occurred. This article presents a narrative of CAI's experiences and promising practices related to training and developing of the Assistor workforce in New York State (NYS). By the end of the second enrollment period (February 2015), NYS trained and certified over 11,000 Assistors (1); CAI trained fifteen percent of this total workforce. As a result of this intensive workforce training effort, NYS observed extremely high rates of facilitated enrollment, and overall success with the roll-out process. Through this initiative, CAI has garnered key insights for other organizations that engage in similar work, as well as state policymakers considering how to integrate and bolster the Assistor programs in their states. These lessons include: the necessity of ensuring that Assistors are armed with all technical concepts and messages; ensuring that Assistors are motivated to work through a change process; the constructive feedback process that can occur when these Assistors directly communicate issues to the state; and the transformation of public opinion that can occur when Assistors provide good customer service and can effectively promote statewide and federal ACA policies and benefits.


Reference Dependence in Bayesian Reasoning: Value Selection Bias, Congruence Effects, and Response Prompt Sensitivity.
This work examines the influence of reference dependence, including value selection bias and congruence effects, on diagnostic reasoning. Across two studies, we explored how dependence on the initial problem structure influences the ability to solve simplified precursors to the more traditional Bayesian reasoning problems. Analyses evaluated accuracy and types of response errors as a function of congruence between the problem presentation and question of interest, amount of information, need for computation, and individual differences in numerical abilities. Across all problem variations, there was consistent and strong evidence of a value selection bias in that incorrect responses almost always conformed to values that were provided in the problem rather than other errors including those related to computation. The most consistent and unexpected error across all conditions in the first experiment was that people were often more likely to utilize the superordinate value (N) as part of their solution rather than the anticipated reference class values. This resulted in a weakened effect of congruence, with relatively low accuracy even in congruent conditions, and a dominant response error of the superordinate value. Experiment 2 confirmed that the introduction of a new sample drew attention away from the provided reference class, increasing reliance on the overall sample size. This superordinate preference error, along with the benefit of repeating the PPV reference class within the question, demonstrated the importance of reference dependence based on the salience of information within the response prompt. Throughout, higher numerical skills were generally associated with higher accuracy, whether calculations were required or not.


Autoradiographic localization of beta-adrenergic receptors in rabbit eye.
Using an in vitro autoradiography, beta-adrenergic receptors were localized in the rabbit eye. Autoradiograms were generated by apposition of isotope-sensitive film to slide-mounted eye sections, labelled with [125I](-)Iodocyanopindolol. A high density of silver grains was obtained in conjunctival, corneal and ciliary process epithelium. Binding sites were also present in corneal endothelium, iris epithelium, lens epithelium, choroid and extraocular muscles. In some areas, retina was also labelled. Studies with beta-adrenergic compounds showed that the majority of beta-adrenergic receptors, detectable by autoradiography, were of the beta2 type in the rabbit eye.