Cardiac swelling-induced chloride current depolarizes canine atrial myocytes.
The effect of the cardiac swelling-induced chloride current (I(Cl,swell)) on the transmembrane potential was examined. Osmotic swelling affected the resting potassium current through an apparent dilution of intracellular potassium. Inflating cells by applying positive pressure to the patch electrode prevented the effect on the resting potassium current. Inflation depolarized dog atrial myocytes when the recording electrodes contained either 17 or 42 mM Cl-. The depolarization coincided with activation of I(Cl,swell) and was antagonized by the chloride-channel blocker niflumic acid. Substituting extracellular chloride with the more permeant ion SCN- shifted the reversal potential for I(Cl,swell) to more negative values and antagonized inflation-induced depolarization. The depolarization was accentuated by replacing extracellular chloride with a less permeant ion, aspartate. We conclude that activation of I(Cl,swell) in atrial cells causes significant depolarization of the resting membrane. The outward rectification of I(Cl,swell) and the high cell membrane resistance during the action potential plateau suggest that I(Cl,swell) will also have significant effects on atrial action potential configuration.


[Diagnosis and surgical treatment of liver echinococcosis].
The results of surgical treatment of more than 600 patients with liver echinococcosis are analysed. The accuracy of ultrasound in diagnosis of the character of the damage is 88%; the combination of ultrasound methods with serology tests and computer tomography has increased the accuracy to 98-100%. New treatment approaches have been proposed depending on a character, location and extent of liver damage. The improvement of surgical technique made it possible to decrease the frequency of postoperative morbidity to 17.4% and mortality-to 3%.


Surgical treatment of metastases from renal cell carcinoma.
Even if the number of curable renal cancers increased during the last decades, there is still a considerable amount of patients with distant metastases, evidenced at diagnosis or during the follow-up, without real curative therapeutic options. In the period between January 1983 and December 2003 we observed 252 metastatic patients among the 1187 surgically treated for renal cancer (21.2%). The metastatic disease was evidenced at the diagnosis of renal tumour in 118 patients (9.9%), during the follow up at a mean distance of 18.6 months in 134 (11.3%) and was in a single organ in 200 patients, in multiple sites in 52. A surgical treatment of metastases was performed in 113 cases, associated with chemo-immunotherapy in 16. Conversely, 44 patients received chemo-immunotherapy alone, 18 radiotherapy, and in the remaining 77 cases no curative therapies were applied. The patients with a single-site metastasis who underwent of metastases removal, especially when pulmonary or adrenal, showed a better prognosis than the ones otherwise treated, while in the patients with bony metastases, multiple-site metastases and the ones who did not receive any curative therapies an extremely dismal prognosis was evidenced. However, a large amount of the patients with a single-site metastasis (79% on 159 treated patients) had a relapse of the disease, even when surgically treated (69%). At present, in the lack of any effective systemic therapies for metastatic renal cancer, surgery offers better survival rates than other choices (chemo-immunotherapy or radiotherapy). Thus, even if the initial bias in the selection of patients is surely significant, in our opinion, each patient with good performance status and a resectable metastatic lesion, better if pulmonary or adrenal, should undergo surgical treatment of metastases, that could provide long-term survival in a small part of the patients. The high rate of relapses remarks the actual need of an effective systemic therapy both for the patients who can and cannot undergo surgery for their metastatic disease.


Internuclear Ophthalmoplegia Secondary to Cocaine Abuse.
Purpose. To report a case of internuclear ophthalmoplegia (INO) caused by cocaine. Method. We report a case of a 54-year-old female who presented with a left INO three days after snorting cocaine, and we review the literature. Results. MRI of the brain demonstrated several small abnormal foci in the pons on FLAIR and diffusion weighted imaging consistent with ischemic infarction. The patient's symptoms remained stable throughout her hospitalization. She was sent to a rehabilitation facility and was lost to follow-up. Conclusion. In cases of extraocular movement abnormalities, it is important to inquire about recreational drug use.


Oligopeptides as full-length New Delhi metallo-β-lactamase-1 (NDM-1) inhibitors.
'Superbug' bacteria producing NDM-1 enzyme causing wide public concern were first detected in a patient who visited India in 2008. It's an effective approach to combining β-lactam antibiotics with NDM-1 inhibitor for treating NDM-1 producing strain infection. In our research, we designed ten oligopeptides, tested IC50 values against NDM-1 enzyme, determined the MIC values of synergistic antibacterial effect and explored the binding model. We found that the oligopeptides 2 (Cys-Phe) and 5 (Cys-Asp) respectively presented IC50 values of 113 μM and 68 μM and also displayed favorable synergistic effects of the inhibitors in combination with ertapenem against genetic engineering-host E. coli BL21 (DE3)/pET30a-NDM-1 and a clinical isolate of P. aeruginosa with blaNDM-1. Flexible docking and partial charge study suggested the interaction between oligopeptide and NDM-1. Three types of action effects, hydrogen bond, electrostatic effect and π-π interaction, contributed to the inhibitory activities.


Would Be Prophylactic Administrations of Low Concentration of Alendronate an Alternative for Improving the Craniofacial Bone Repair? A Preliminary Study Focused in the Period of Cellular Differentiation and Tissue Organization.
Alendronate (ALN) is a nitrogen-bisphosphonate that may induce an anabolic effect on craniofacial bone repair when administrated in low doses. Based on this premise, this study analyzed the influence of prophylactic low doses of ALN on bone healing in defects created in rabbit mandible. A 5 × 2-mm diameter deep defect was created in the calvaria of 28 rabbits. Fourteen of these rabbits received previously 50 μg/kg of 1% sodium ALN for 4 weeks, while the other rabbits received only 0.9% physiological saline solution (control). Animals were euthanized at 15 and 60 days postsurgery (n = 7), and the data were analyzed using histomorphometry and immunohistochemistry using the anti-CD34, bone morphogenetic protein -2 (BMP-2), and transforming growth factor (TGF)-β1 antibodies. On the 15th day postsurgery, the specimens that received previous treatment with ALN demonstrated large vascular lumen and intense positivity to CD34 either concentrated in endothelium or cells spread among the reparative tissue. These results coincided with intense positivity for BMP-2+ cells and TGF-β1 that was concentrated in both cells and perivascular area. In contrast, the control group revealed scarce cells that exhibited CD34, BMP-2+, and the TGF-β1 was restricted for perivascular area on well-formed granulation tissue. These patterns of immunohistochemical result, especially found on the 15th day of analysis, seem to be responsible for the development of larger quantities of bone matrix in the specimens that receive ALN on the 60th day postsurgery. These preliminary results showed that the prophylactic administration of low doses of ALN might be an alternative to craniofacial bone craniofacial bone repair because it increases the immunopositivity for TGF-β1 and consequently improves the CD34+ and BMP-2+ cells on reparative sites.


Exogenous supplement of glucagon like peptide-1 protects the heart against aortic banding induced myocardial fibrosis and dysfunction through inhibiting mTOR/p70S6K signaling and promoting autophagy.
Mammalian target of rapamycin (mTOR) and a ribosomal protein S6 kinase (p70S6K) mediate tissue fibrosis and negatively regulate autophagy. This study aims to investigate whether glucagon-like peptide-1 (GLP-1) analog liraglutide protects the heart against aortic banding-induced cardiac fibrosis and dysfunction through inhibiting mTOR/p70S6K signaling and promoting autophagy activity. Male SD rats were randomly divided into four groups (n = 6/each group): sham operated control; abdominal aortic constriction (AAC); liraglutide treatment during AAC (0.3 mg/kg, injected subcutaneously twice daily); rapamycin treatment during AAC (0.2 mg/kg/day, administered by gastric gavage). Relative to the animals with AAC on week 16, liraglutide treatment significantly reduced heart/body weight ratio, inhibited cardiomyocyte hypertrophy, and augmented plasma GLP-1 level and tissue GLP-1 receptor expression. Phosphorylation of mTOR/p70S6K, populations of myofibroblasts and synthesis of collagen I/III in the myocardium were simultaneously inhibited. Furthermore, autophagy regulating proteins: LC3-II/LC3-I ratio and Beclin-1 were upregulated, and p62 was downregulated by liraglutide. Compared with liraglutide group, treatment with rapamycin, a specific inhibitor of mTOR, compatibly augmented GLP-1 receptor level, inhibited phosphorylation of mTOR/p70S6K and expression of p62 as well as increased level of LC3-II/LC3-I ratio and Beclin-1, suggesting that there is an interaction between GLP-1 and mTOR/p70S6K signaling in the regulation of autophagy. In line with these modifications, treatment with liraglutide and rapamycin significantly reduced perivascular/interstitial fibrosis, and preserved systolic/diastolic function. These results suggest that the inhibitory effects of liraglutide on cardiac fibrosis and dysfunction are potentially mediated by inhibiting mTOR/p70S6K signaling and enhancing autophagy activity.


Graphic cigarette pack warnings do not produce more negative implicit evaluations of smoking compared to text-only warnings.
Graphic warnings (GWs) on cigarette packs are widely used internationally with the aim of reducing smoking behavior. In the current study, we investigated whether GWs influence implicit evaluations of smoking, a potential moderator of smoking behavior, as measured with an Implicit Association Test (IAT). Results showed that viewing a GW did not produce more negative implicit evaluations of smoking for daily smokers, occasional smokers, or non-smokers, compared to viewing a text-only warning. If anything, effects were in the direction of evaluations of smoking being more positive after certain participants (i.e., daily and occasional smokers) viewed a GW. We also did not find any beneficial effects of GWs on explicit evaluations of smoking. These results contrast with the observation that non-smokers and occasional smokers (but not daily smokers) believed that GWs would be more effective than the text-only warnings. We discuss implications and limitations of these findings and provide recommendations for improving the effectiveness of cigarette pack warnings on implicit evaluations.


Omega-3 Supplementation Prevents Short-Term High-Fat Diet Effects on the α7 Nicotinic Cholinergic Receptor Expression and Inflammatory Response.
The study is aimed at investigating if PUFA supplementation could prevent the effects of a short-term HFD on α7nAChR expression and on the severity of sepsis. Swiss mice were used for the in vivo experiments. For the in vitro experiments, we used a microglia cell line (BV-2) and a hepatoma cell line (Hepa-1c1c7) derived from mice. The animals were either fed standard chow, fed a short-term HFD (60%), or given supplementation with omega-3 fatty acid (2 g/kg or 4 g/kg bw) for 17 days, followed by a short-term HFD. Endotoxemia was induced with an intraperitoneal (i.p.) lipopolysaccharide injection (LPS, 5 or 12 mg/kg), and sepsis was induced by subjecting the animals to cecal ligation and puncture (CLP). BV-2 and Hepa-1c1c7 cells were treated with LPS (100 and 500 ng/mL, respectively) for 3 hours. RT-PCR or Western blotting was used to evaluate α7nAChR expression, inflammatory markers, DNMT1, and overall ubiquitination. LPS and HFD reduced the expression of α7nAChR and increased the expression of inflammatory markers. Omega-3 partially prevented the damage caused by the HFD to the expression of α7nAChR in the bone marrow and hypothalamus, decreased the inflammatory markers, and reduced susceptibility to sepsis-induced death. Exposing the BV-2 cells to LPS increased the protein content of DNMT1 and the overall ubiquitination and reduced the expression of α7nAChR. The inflammation induced by LPS in the BV-2 cell decreased α7nAChR expression and concomitantly increased DNMT1 expression and the ubiquitinated protein levels, indicating the participation of pre- and posttranscriptional mechanisms.


Siglec-15 Promotes Evasion of Adaptive Immunity in B-cell Acute Lymphoblastic Leukemia.
Siglec-15 (Sig15) has been implicated as an immune checkpoint expressed in solid tumor-infiltrating macrophages and is being targeted in clinical trials with mAbs to normalize the tumor immune microenvironment and stimulate antitumor immunity. However, the role of Sig15 in hematologic malignancies remains undefined. Sig15 mRNA and protein expression levels in hematologic malignancies were determined from publicly available databases, cell lines, and primary patient samples. Human B-cell acute lymphoblastic leukemia (B-ALL) cell lines were used to identify signaling pathways involved in the regulation of Sig15 expression. Secreted/soluble Sig15 and cytokine levels were measured from the plasma of children with leukemia and healthy controls. Knockdown and knockout of Siglec15 in a murine model of B-ALL was used to evaluate the effect of leukemia-derived Sig15 on the immune response to leukemia. We observed pathologic overexpression of Sig15 in a variety of hematologic malignancies, including primary B-ALL samples. This overexpression was driven by NFκB activation, which also increased the surface localization of Sig15. Secreted/soluble Sig15 was found to circulate at elevated levels in the plasma of children with B-ALL and correlated with an immune-suppressive cytokine milieu. Genetic inhibition of Sig15 in murine B-ALL promoted clearance of the leukemia by the immune system and a marked reversal of the immune-privileged leukemia bone marrow niche, including expanded early effector CD8+ T cells and reduction of immunosuppressive cytokines. Thus, Sig15 is a novel, potent immunosuppressive molecule active in leukemia that may be targeted therapeutically to activate T lymphocytes against leukemia cells. We demonstrate that Sig15 is overexpressed in hematologic malignancies driven by NFκB, is required for immune evasion in a mouse model of leukemia, and, for the first time, that it circulates at high levels in the plasma of children with leukemia.


A comparative analysis of phosphoproteome in ovine muscle at early postmortem in relationship to tenderness.
Tenderness is considered to be the most important quality characteristic of meat as it is the main cause of unacceptability of meat. Post-translational modification regulates protein functions that involve in postmortem changes in muscle and meat quality formation. Specifically, phosphorylation was proved to regulate postmortem glycolytic rates and meat tenderisation. However, the relationship between protein phosphorylation and meat tenderness remains unclear. This study examined the phosphoproteomes found in ovine muscle with different degrees of tenderness over time (at 0.5 h, 4 h, and 24 h postmortem). This study detected five, eight and nine phosphoprotein spots (>two-fold change, P < 0.05) at each respective time point. The different phosphoproteins found included glyceraldehyde-3-phosphate dehydrogenase, tropomyosin α-1 chain, pyruvate kinase, myosin binding protein H, glycogen phosphorylase, α-actinin-3, and an uncharacterised protein (GN, myosin-binding protein C2, MYBPC2). Most of the different phosphoproteins maintained sarcomeric functions, or were involved in glycometabolism. Phosphorylation levels of multiple proteins that are involved in glycolysis, muscle contraction or sarcomeric structure integrity were identified in ovine muscles with different tenderness. The differential phosphorylation of these proteins explains in part the difference in meat tenderness. © 2017 Society of Chemical Industry.


Sexual behaviour and contraceptive practice of future doctors in Southwest Nigeria.
The sexual behaviour and contraceptive practice of 498 clinical students of a randomly selected medical college in Southwest Nigeria was studied in June 2003. More than two-thirds (67.5%) of the students had (ever had) sexual intercourse while 49.8% of them had ever used contraception. Only 26.1% of the 119 sexually active students used contraception during their last sexual intercourse. The most common contraceptive methods ever used by the students were the condom (54.6%) and rhythm method (39.5%) though a third of them incorrectly identified the limits of the fertile period. Contraception for single sexually active students was disapproved by 11.2% of the participants while 9.8% of them regarded avoidance of HIV patients in the hospital as a preventive measure against HIV infection. This survey reinforces the need for integration of a suitable sexuality course into our medical undergraduate curriculum in order to facilitate the delivery of reproductive health programmes in the future.


Problems Associated With Access to Renal Replacement Therapy: Experience of the Sindh Institute of Urology and Transplantation.
The prevalence of end-stage renal disease is increasing worldwide. It is also one of the main health problems in Pakistan. Currently, hemodialysis represents the main mode of treatment for patients with end-stage renal disease in this country. Despite 24-hour free dialysis at the Sindh Institute of Urology and Transplantation (Karachi, Pakistan), a significant number of patients do not turn up for regular dialysis or miss regular sessions of dialysis. We conducted this study to identify and highlight the factors leading to poor compliance with regular hemodialysis treatment despite free dialysis treatment offered at our center. In 2014, 4565 patients with end-stage renal disease were registered at the Sindh Institute of Urology and Transplantation. Among these, 610 patients (13.4%) missed more than 2 sessions of dialysis and were included in the present study. Patients provided written informed consent before study participation. Data were collected from a questionnaire survey and analyzed by SPSS software (SPSS: An IBM Company, version 20.0, Chicago, IL, USA). Despite 24-hour dialysis facilities, the patient drop-out rate (779; 18%) was high. In addition, a significant minority of patients (610; 13.4%) was erratic in adherence to maintenance hemodialysis schedules, with > 2 missed appointments. The mean age of these 610 patients was 33.4 ± 7.4 years, and 345 patients (57%) were males. The main factors leading to poor compliance included cost of travel (33.2%), lack of affordable lodging and boarding facilities near dialysis center (30.9%), long distances from dialysis center (20.1%), and lack of family support (15.6%). This study shows that there is significant drop-out and poor compliance rates for regular dialysis despite free dialysis facilities.


Reduced Expression of RanBPM Is Associated with Poorer Survival from Lung Cancer and Increased Proliferation and Invasion of Lung Cancer Cells In Vitro.
Ran binding protein microtubule-organizing centre (RanBPM), also known as RanBP9, is a scaffold protein conserved through evolution. We investigated the role of RanBPM in human lung cancer. Transcripts of RanBPM were determined in 56 human lung cancers along with paired normal lung tissues using real-time PCR. Association with prognosis was analyzed by online Kaplan-Meier survival analysis. In vitro lung cancer cell functional assays examined the impact of RanBPM-knockdown on cellular growth and invasion. Higher expression of RanBPM was observed in tumor when compared to paired normal lung tissues. Increased RanBPM expression was seen in patients with longer overall and disease-free survival. Knockdown of RanBPM in lung cancer cell lines resulted in increased growth and invasion in vitro. Increased expression of RanBPM associates with postponed disease progression and better prognosis. RanBPM plays an inhibitory role in regulating proliferation and invasion of lung cancer cells.


CXCR4 targeted dendrimer for anti-cancer drug delivery and breast cancer cell migration inhibition.
CXCR4 and its ligand CXCL12 play a critical role in the metastasis of various types of cancer including breast cancer. Breast tumors preferentially metastasize to the lung, bones and distant lymph nodes, secreting high levels of CXCL12. We hypothesized that targeted inhibition of CXCR4 in breast cancer cells should suppress CXCR4-positive tumor cells toward secondary metastatic sites. In the present study, the efficacy of CXCR4 targeted dendrimers carrying DOX (LFC131-DOX-D4) on cellular binding, cytotoxicity, and migration of BT-549-Luc and T47D breast cancer cells was investigated. PAMAM dendrimers encapsulating DOX was surface functionalized with LFC131 peptide which recognized CXCR4 expressed on the surface of breast cancer cells. The LFC131-DOX-D4 bound to breast cancer cells resulting in significantly enhanced in vitro cellular toxicity as compared with non-targeted dendrimers. The LFC131-D4 exhibited remarkable reduced migration of BT-549-Luc breast cancer cells toward chemoattractant. This report demonstrated the potential utility of LFC131-dendrimer conjugates for breast cancer therapy and metastasis.


Endovascular treatment of a large fusiform splenic artery aneurysm with a coaxial technique using a 5-f balloon catheter and a microcatheter.
A coaxial technique was introduced for successful embolization of a large fusiform splenic artery aneurysm in a vessel with a large caliber and a great degree of tortuosity. A standard 5-F angioplasty catheter was placed at the immediate afferent artery for occlusion of arterial inflow into the aneurysm, thereby preventing intraaneurysmal hypertension during embolization of the efferent segment. This was followed by coaxial microcatheterization of the immediate efferent segment for coil embolization, and then embolization of the afferent segment. It is postulated that this approach may improve the safety of embolization of large aneurysms with unfavorable morphology by decreasing the pressure on the aneurysm just after closure of the efferent segment.


Patterns and correlates of physical activity and nutrition behaviors in adolescents.
Knowledge of the prevalence, clustering, and correlates of multiple adolescent health behaviors can inform the design of health promotion interventions. A cross-sectional design was used to assess 878 adolescents aged 11 to 15 years (53.6% girls, 58% non-Hispanic white) recruited in primary care clinics in 2001-2002. Adolescent physical activity (assessed with accelerometers), television viewing time (reported), percent calories from fat, and servings of fruits and vegetables (assessed with multiple 24-hour recalls) were dichotomized into meeting or not meeting national guidelines. Parent health behaviors were assessed with self-reported measures. Analyses were conducted in 2006. Fifty-five percent of adolescents did not meet the physical activity guideline, and 30% exceeded 2 hours daily of television viewing time, with boys more active and less sedentary than girls (p <0.01). The majority of the adolescents did not meet dietary guidelines. Nearly 80% had multiple risk behaviors and only 2% met all four guidelines. The number of risk behaviors was associated with being older and being at risk for overweight or being overweight, for boys and girls (p <0.05). Two parent health behaviors-history of smoking and failure to meet the fruits and vegetables guideline-were significantly associated with a higher number of risk behaviors for girls (p <0.05). Eight of ten adolescents in this sample failed to meet guidelines for two or more diet, physical activity, and sedentary risk behaviors. Some parent health behaviors, along with the adolescent's weight status and age, were associated with a higher number of adolescent health risk behaviors.


Metamaterial-based transmit and receive system for whole-body magnetic resonance imaging at ultra-high magnetic fields.
Magnetic resonance imaging (MRI) at ultra-high fields (UHF), such as 7 T, provides an enhanced signal-to-noise ratio and has led to unprecedented high-resolution anatomic images and brain activation maps. Although a variety of radio frequency (RF) coil architectures have been developed for imaging at UHF conditions, they usually are specialized for small volumes of interests (VoI). So far, whole-body coil resonators are not available for commercial UHF human whole-body MRI systems. The goal of the present study was the development and validation of a transmit and receive system for large VoIs that operates at a 7 T human whole-body MRI system. A Metamaterial Ring Antenna System (MRAS) consisting of several ring antennas was developed, since it allows for the imaging of extended VoIs. Furthermore, the MRAS not only requires lower intensities of the irradiated RF energy, but also provides a more confined and focused injection of excitation energy on selected body parts. The MRAS consisted of several antennas with 50 cm inner diameter, 10 cm width and 0.5 cm depth. The position of the rings was freely adjustable. Conformal resonant right-/left-handed metamaterial was used for each ring antenna with two quadrature feeding ports for RF power. The system was successfully implemented and demonstrated with both a silicone oil and a water-NaCl-isopropanol phantom as well as in vivo by acquiring whole-body images of a crab-eating macaque. The potential for future neuroimaging applications was demonstrated by the acquired high-resolution anatomic images of the macaque's head. Phantom and in vivo measurements of crab-eating macaques provided high-resolution images with large VoIs up to 40 cm in xy-direction and 45 cm in z-direction. The results of this work demonstrate the feasibility of the MRAS system for UHF MRI as proof of principle. The MRAS shows a substantial potential for MR imaging of larger volumes at 7 T UHF. This new technique may provide new diagnostic potential in spatially extended pathologies such as searching for spread-out tumor metastases or monitoring systemic inflammatory processes.


Real-time toxicity and metabolic activity tracking of human cells exposed to Escherichia coli O157:H7 in a mixed consortia.
Escherichia coli O157:H7 is a significant human pathogen that is continually responsible for sickness, and even death, on a worldwide scale. While the pathology of E. coli O157:H7 infection has been well studied, the effect of it's multiple resulting cytotoxic mechanisms on host metabolic activity has not been well characterized. To develop a more thorough understanding of these effects, several bioluminescence assays were evaluated for their ability to track both toxicity and host metabolic activity levels in real-time. The use of continuously autobioluminescent human cells was determined to be the most favorable method for tracking these metrics, as its self-sufficient autobioluminescent phenotype was unaffected by the presence of the infecting bacteria and its signal could be measured without cellular destruction. Using this approach, it was determined that infection with as few as 10 CFU of E. coli O157:H7 could elicit cytotoxic effects. Regardless of the initial infective dose, an impact on metabolic expression was not observed until bacterial populations reached levels between 5 × 10(5) and 1 × 10(6) (R(2) = 0.933), indicating that a critical bacterial infection level must be reached prior to the onset of cytotoxic effects. Supporting this hypothesis, it was found that cells displaying infection-mediated metabolic activity reductions could recover to wild type metabolic activity levels if the infecting bacteria were removed prior to cell death. These results indicate that rapid treatment of E. coli O157:H7 infection could serve to limit host metabolic impact and reduce overall host cell death.


Sustained high rates of morphological evolution during the rise of tetrapods.
The fish-to-tetrapod transition is one of the most iconic events in vertebrate evolution, yet fundamental questions regarding the dynamics of this transition remain unresolved. Here, we use advances in Bayesian morphological clock modelling to reveal the evolutionary dynamics of early tetrapodomorphs (tetrapods and their closest fish relatives). We show that combining osteological and ichnological calibration data results in major shifts on the time of origin of all major groups of tetrapodomorphs (up to 25 million years) and that low rates of net diversification, not fossilization, explain long ghost lineages in the early tetrapodomorph fossil record. Further, our findings reveal extremely low rates of morphological change for most early tetrapodomorphs, indicating widespread stabilizing selection upon their 'fish' morphotype. This pattern was broken only by elpistostegalians (including early tetrapods), which underwent sustained high rates of morphological evolution for ~30 Myr during the deployment of the tetrapod body plan.


Nasogastric tube knotting over the epiglottis: a cause of respiratory distress.
Nasogastric tube placement can cause ulceration and bleeding from the nose, pharynx, esophagus, and stomach. Its accidental placement into the tracheopulmonary system may lead to pneumothorax, hemothorax, or even death. We report a case of its knotting over the epiglottis, leading to life-threatening respiratory distress.


Left atrial thrombus after placement of watchman device.
Atrial fibrillation is an irregular rhythm with increased risk of morbidityand mortality. Commonly due to thromboembolism at the left atrialappendage. Guideline therapy for atrial fibrillation is anticoagulation.Alternative treatment includes closure with the Watchman device. Wepresent a case of Watchman device-related thrombus seven monthsafter placement.


Maternal obesity (Class I-III), gestational weight gain and maternal leptin levels during and after pregnancy: a prospective cohort study.
Maternal obesity is accompanied by maternal and fetal complications during and after pregnancy. The risks seem to increase with degree of obesity. Leptin has been suggested to play a role in the development of obesity related complications. Whether maternal leptin levels differ between obese and morbidly obese women, during and after pregnancy, have to our knowledge not been previously described. Neither has the association between maternal leptin levels and gestational weight gain in obese women. The aim was to evaluate if maternal plasma leptin levels were associated with different degrees of maternal obesity and gestational weight gain. Prospective cohort study including women categorized as obesity class I-III (n = 343) and divided into three gestational weight gain groups (n = 304). Maternal plasma leptin was measured at gestational week 15, 29 and 10 weeks postpartum. Maternal Body Mass Index (BMI) was calculated from early pregnancy weight. Gestational weight gain was calculated using maternal weight in delivery week minus early pregnancy weight. The mean value and confidence interval of plasma-leptin were analysed with a two-way ANOVA model. Interaction effect between BMI and gestational weight gain group was tested with a two-way ANOVA model. The mean maternal leptin concentrations were significantly higher in women with obesity class III compared to women in obesity class I, at all times when plasma leptin were measured. The mean leptin concentrations were also significantly higher in women with obesity class II compared to women in obesity class I, except in gestational week 29. There was no difference in mean levels of plasma leptin between the gestational weight gain groups. No significant interaction between BMI and gestational weight gain group was found. Plasma leptin levels during and after pregnancy were associated with obesity class but not with degree of gestational weight gain. These results are in concordance with epidemiological findings where the risk of obstetric complications increases with increased maternal obesity class. The effect on obstetric outcome by degree of gestational weight gain is less pronounced than the adverse effects associated with maternal obesity.


NOMID: the radiographic and MRI features and review of literature.
Neonatal onset multisystem inflammatory disease (NOMID) is a rare autoinflammatory disorder, which manifests early in infancy. We describe a case of a 10-year-old boy who has been unwell since infancy. He presented with urticarial rash, intermittent fever and hepatosplenomegaly followed by progressive arthropathy. His joint symptoms started at two years of age, which progressively involved multiple joints, resulting in bone and joint deformities. A series of joint radiographs demonstrated bizarre enlarging physeal mass with heterogenous calcification. Magnetic resonance imaging (MRI) of the involved right ankle and knee showed characteristic thickened and calcified physeal lesions, which enhanced post-gadolinium. This debilitating disease is also known to involve the central nervous system and eyes. This case report aims to highlight the conventional radiographic and magnetic resonance imaging (MRI) findings of this physeal abnormality in NOMID syndrome.


TP53 gene mutations and CCND1 gene amplification in head and neck squamous cell carcinoma cell lines.
Mutations of the tumor-suppressor gene TP53 and amplification of CCND1 gene have been reported to occur frequently in head and neck squamous cell carcinomas (HNSQCC). In experimental systems, TP53 mutations have been shown to lead to genomic instability, including an increased propensity for gene amplification. We have examined 16 HNSQCC cell lines for the association between TP53 over-expression/mutation and CCND1 amplification. p53 over-expression was detected in 50% of the cell lines by immunohistochemistry using the monoclonal antibody (MAb) PAb1801. TP53 mutations were also detected in 50% of the cell lines by analysis of single-strand conformation polymorphism (SSCP) and DNA sequencing of exons 4 through 9. Six cell lines showed TP53 mutations and over-expression of the protein, 2 cell lines showed TP53 mutations but no p53 expression, and 2 cell lines showed over-expression of p53 protein but no TP53 gene mutations. CCND1 amplification was found in 38% of the cell lines by Southern blot analysis. Only 1 cell line showed both TP53 mutation and CCND1 amplification, whereas 7 of 8 cell lines with TP53 mutations had no CCND1 amplification. pRb expression was detected by Western blot analysis, and the level of pRb did not correlate with either CCND1 amplification or TP53 mutation. Our findings suggest that TP53 mutation and CCND1 amplification are common genetic alterations in HNSQCC and that the occurrence of either genetic event may be sufficient to abrogate normal cell cycle control.


Study of behavioral and psychological symptoms of dementia in Taiwan.
The behavioral and psychological symptoms of dementia (BPSD) are common serious problems that affect the quality of life for both the patients with such symptoms as well as their caregivers. BPSD present a major challenge in the medical management of patients and are the major cause of institutionalization. Alzheimer's Disease (AD) is the most common type of dementia in Taiwan. I performed a systematic literature review on BPSD studies and found that Taiwanese patients with AD exhibit many of the BPSD. Studies showed that between 30% and 63% of Taiwan's AD patients experienced delusion. Hallucination occurred less frequently, which ranged from 21% to 26%. Anxiety occurred in 35-76% of patients and depression 22-50%, sleep abnormalities 26-61% and 39-46%. The differences in the prevalence of BPSD might result from the different clinical settings and evaluation instruments. The prevalence and clinical manifestations of BPSD in Taiwan are similar to Western reports and it suggests that most of BPSD are neurobiologically determined. Based on differing cultural backgrounds, the interpretation of agitation and apathy might differ, so, the development of cross-cultural applicable criteria and rating scales for the assessment and treatment of BPSD are important for future studies.


Tetramerization of 3-methyl-cyclopropene-3-carbonitrile: a novel CN-alder-ene reaction.
At elevated temperatures 3-methyl-cyclopropene-3-carbonitrile 1 was found to tetramerize giving compound 2 (3-methyl-2,3-bis(2-t-methyl-2-c-cyanocyclopropyl)-1-(2-t-methyl-2-c,3-c-dicyanocyclopropyl)-cyclopropene) in good yields. This is the first example of Alder-ene type oligomerization of a 3,3-disubstituted cyclopropene. On the basis of the product geometry and stereoselective character of the reaction, a mechanism of formation of 2 involving CN-Alder-ene reaction was proposed. DFT modeling of the mechanism has shown that the CN-Alder-ene reaction is possible as a stepwise process involving a biradical intermediate.


Nutritional and end-use perspectives of sprouted grains: A comprehensive review.
Scientific literature is evident that the germinated seeds possess a promising potential for essential nutrients, flavors, and textural attributes over nongerminated grain. In recent decades, sprouting has also been investigated as a potential green food engineering technique to boost the nutritive profile of grains. Sprouting grains have multifold applications in different fields such as baking, pharmaceutical, and cosmetic industries. During sprouting, shifting of molecular structures to macroscopic takes place. Sprouting reactivates the grain metabolism which leads to the catabolism and degradation of antinutrient and macronutrient compounds. These modifications have an effect on human health and on the nutritional content of the foodstuffs. Sprouting grains have high bioactivity against diabetes and cancer. Germination is also an outstanding green food development technique to increase the seed nutritive profile in terms of quality. The present review focuses on the sprouting of grains, changes in nutritional profile, and the technological exploration of sprouted grains.


Effect of pasture and intensive feeding systems on the carcass and meat quality of buffalo.
This work was carried out to evaluate the effect of pasture (PA) feeding on buffalo meat quality compared with buffaloes reared intensively with the use of corn silage as a forage base or alternatively with polyphite meadow hay (PH). Thirty Mediterranean bull buffaloes were distributed into three experimental diet groups: maize silage (MS), PH, and PA. The animals were slaughtered at a live weight of 250 kg, and carcass and meat quality were evaluated. After 7 days of ageing, physical and chemical parameters of longissimus thoracis muscle were determined. To evaluate lipid oxidation the thiobarbituric acid reactive substances was tested at 7 and 14 days, and also the fatty acid profile was recorded by gas chromatography. The PA group, even if it showed carcass parameters lower than those of the silage maize group, reported a good meat percentage (60.59% vs 58.46%, respectively) and lower fat percentage (p<0.001). PA-fed animals showed meat redness, and even if only on raw meat, shear force was higher than the others. Low values of conjugate linoleic acid, polyunsaturated fatty acids, and n-3 were reported in the silage maize group. Principal component analysis (PCA) clearly showed the influence of different diets on meat quality, and PCA1 and PCA2 explained 82% of the variability. Buffaloes reared on PA had meat with high nutritional value even if they showed poor carcass performance compared to the animals fed on MS. Buffaloes fed on polyphite hay were in an intermediate position, similar to grazing animals, according to the same nutritional determinations.


Self-clearance mechanism of mitochondrial E3 ligase MARCH5 contributes to mitochondria quality control.
MARCH5, a mitochondrial E3 ubiquitin ligase, controls mitochondrial dynamics proteins and misfolded proteins, and has been proposed to play a role in mitochondria quality control. However, it remains unclear how mutant MARCH5 found in cancer tissues is removed from cells. Here, we show that mutation in the MARCH5 ligase domain increased its half-life fourfold, resulting in a drastic increase in its protein level. Abnormal accumulation of the E3 ligase-defective MARCH5 mutants MARCH5(H43W) and MARCH5(C65/68S) was diminished by overexpression of active MARCH5(WT) ; the mutant proteins were degraded through the ubiquitin-proteasome pathway. Coimmunoprecipitation revealed that MARCH5 forms homodimers, and that substitution of Gly to Leu at the first putative GxxxG dimerization motif, but not the second, resulted in a loss of dimeric interaction. Moreover, overexpression of the dimerization-defective mutant MARCH5(4GL) could not decrease the level of accumulated MARCH5(H43W) , suggesting that dimerization of MARCH5 is necessary for self-clearance. Abnormal accumulation of MARCH5(H43W) and mitochondrial hyperfusion led to NF-ĸB activation, which was suppressed by overexpression of MARCH5(WT) . Together, the data reveal a self-protective mechanism involving MARCH5, which can target its own dysfunctional mutant for degradation in order to maintain mitochondrial homeostasis.


Do alcohol-related consequences and how they are evaluated predict consumption during and days until the next drinking event?
Objective: Alcohol-related consequences are most often examined as outcomes of alcohol use. However, it is also possible that experiencing consequences may predict future drinking behavior. The predictive power of consequences on future drinking behavior may involve both objective experiences of consequences and subjective evaluations of those consequences (i.e., how positive, how negative). The purpose of the present study was to understand how positive and negative alcohol-related consequences-and evaluations of those consequences-predict elements of the next drinking event among college students. Method: 96 participants reported alcohol use and related consequences over a 28-day daily assessment period. Results: Survival analysis and multilevel modeling were used to examine the influence of positive and negative consequences from a given drinking event on latency to and number of drinks consumed at the next drinking event. Contrary to hypotheses, subsequent drinking was not impacted by recent consequences nor how they were perceived. Conclusions: Though theoretically, experiencing alcohol consequences may impact proximal drinking behavior, findings suggest that, in the current sample, other factors have greater importance in the latency between drinking events and amount of alcohol consumed. Future work should continue to identify event-level predictors that impact behavior at the next drinking event, and ways drinkers attempt to avoid repetition of drinking consequences other than simply drinking less (e.g., protective behavioral strategies), as such factors would be valuable targets for intervention. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


[Subjective body experience in hypochondria and somatoform disorders].
Limitations and difficulties of clinical characteristics of mental disorders, manifesting in symptoms of body sphere, are described. The conceptions of body and subjective body experience, assuming that body sensations are involved in self-identification and self-ego formation and connected with cognitive, social and cultural aspects of subjective experience, are discussed. To evaluate phenomenological, biographical, psychodynamic, cognitive and socio-cultural context of body sensations appearance in somatoform mental disorders, the multi-axial model of subjective body experience description is suggested.


Analysis on image quality of a holographic lens with a non-converging signal wave for compact near-eye displays.
We analyze an image quality of a holographic lens (HL) in order to implement compact near-eye displays using a flat-panel-type micro-display panel. The proposed method utilizes a non-converging signal wave in a fabrication process of the HL, so that it provides affordable eye-box size with minimizing the aberration due to rays in the off-Bragg condition. For analyzing and optimizing the HL based on the non-converging signal wave, we introduce a comprehensive analysis model for an assessment of the image quality in the HL. The analysis model, inspired from the conventional lens design strategy for near-eye displays, evaluates the focal spot quality for incident rays forming each pixel with considering the on- and off-Bragg diffraction. The theoretical analysis is validated by simulation results using a volume hologram model in Zemax OpticStudio. As experimental verifications, we realize a prototype system using photopolymer-based HLs in a green color with the high transmittance of 89.3%. The image quality of the HLs is analyzed, which coincides well with the proposed analysis and assessment metric. By building a compact experimental setup employing the HL and a micro-organic light emitting diode display, we present see-through images with 8.0 mm of eye-box with reduced aberrations.


A Novel Transwell Blood Brain Barrier Model Using Primary Human Cells.
Structural alterations and breakdown of the blood brain barrier (BBB) is often a primary or secondary consequence of disease, resulting in brain oedema and the transport of unwanted substances into the brain. It is critical that effective in vitro models are developed to model the in vivo environment to aid in clinically relevant research, especially regarding drug screening and permeability studies. Our novel model uses only primary human cells and includes four of the key cells of the BBB: astrocytes, pericytes, brain microvascular endothelial cells (HBMEC) and neurons. We show that using a larger membrane pore size (3.0 μM) there is an improved connection between the endothelial cells, astrocytes and pericytes. Compared to a two and three cell model, we show that when neurons are added to HBMECs, astrocytes and pericytes, BBB integrity was more sensitive to oxygen-glucose deprivation evidenced by increased permeability and markers of cell damage. Our data also show that a four cell model responds faster to the barrier tightening effects of glucocorticoid dexamethasone, when compared to a two cell and three cell model. These data highlight the important role that neurons play in response to ischaemia, particularly how they contribute to BBB maintenance and breakdown. We consider that this model is more representative of the interactions at the neurovascular unit than other transwell models and is a useful method to study BBB physiology.


Effects of extraction methods on the rheological properties of polysaccharides from onion (Allium cepa L.).
In this work we described the rheological properties of polysaccharides (HBSS, CHSS, DASS, CASS) sequentially extracted from onion (Allium cepa L.). Four onion polysaccharides (ACLPs) solutions resulted into significant differences on their rheological properties. ACLPs solutions showed non-Newtonian shear-thinning behavior over the range of 0.5-2.5%. At concentration of 1%, the apparent viscosity of CHSS was observed to be the highest. The apparent viscosity of ACLPs solutions decreased with the acidic pH (4.0) or alkaline pH (10.0) which was further declined at higher temperature (90 °C). After the addition of various salts, ACLPs had apparent differences on apparent viscosity. The G' (storage modulus) and G″ (loss modulus) of ACLP solutions were increased with increasing oscillation frequency. Moreover, the crossover value of oscillation frequency gradually decreased with increasing concentration of ACLPs. Our results exhibited that among the ACLPs, CHSS can be used as supplements in the food industry as thickening agent, gelling agent and stabilizer.


Evaluating the Preparedness of Indian States against COVID-19 Pandemic Risk: A Fuzzy Multi-criteria Decision-Making Approach.
The preparedness of Indian states and union territories (UTs) against the COVID-19 pandemic has been evaluated. Ten parameters related to demographic, socioeconomic, and healthcare aspects have been considered and the performances of 27 states and three UTs have been evaluated applying the Fuzzy Analytic Hierarchy Process. Opinions of medical experts have been considered to ascertain the relative importance of decision criteria as well as subcriteria. The scores of various states and UTs in each of the decision subcriteria have been calculated by using the secondary data collected from authentic sources. It is found that Kerala and Bihar are the best prepared and worst prepared states, respectively, to combat COVID-19 pandemic. Karnataka, Goa, and Tamil Nadu have very good preparedness whereas Chhattisgarh, Jharkhand, and Bihar have very poor preparedness. Maharashtra, the most affected state in India, has average preparedness. As around 650 million people are vulnerable due to the poor and very poor preparedness of their states, the country needs to make region specific mitigation strategies to combat the COVID-19 pandemic and the preparedness map will be helpful in that direction.


Platelet transfusion for patients with cancer.
Platelet transfusion is a critical and often necessary aspect of managing cancer. Low platelet counts frequently lead to bleeding complications; however, the drugs used to combat malignancy commonly lead to decreased production and destruction of the very cell whose function is essential to stop bleeding. The transfusion of allogeneic platelet products helps to promote hemostasis, but alloimmunization may make it difficult to manage other complications associated with cancer. The literature relating to platelet transfusion in patients with cancer was reviewed. Platelet storage, dosing, transfusion indications, and transfusion response are essential topics for health care professionals to understand because many patients with cancer will require platelet transfusions during the course of treatment. The workup and differentiation of non-immune-mediated compared with immune-mediated platelet refractoriness are vital because platelet management is different between types of refractoriness. A combination of appropriate utilization of platelet inventory and laboratory testing coupled with communication between those caring for patients with cancer and those providing blood products is essential for effective patient care.


Story of Rubidium-82 and Advantages for Myocardial Perfusion PET Imaging.
Rubidium-82 has a long story, starting in 1954. After preclinical studies in dogs showing that myocardial uptake of this radionuclide was directly proportional to myocardial blood flow (MBF), clinical studies were performed in the 80s leading to an approval in the USA in 1989. From that time, thousands of patients have been tested and their results have been reported in three meta-analyses. Pooled patient-based sensitivity and specificity were, respectively, 0.91 and 0.90. By comparison with (99m)Tc-SPECT, (82)Rb PET had a much better diagnostic accuracy, especially in obese patients with body mass index ≥30 kg/m(2) (85 versus 67% with SPECT) and in women with large breasts. A great advantage of (82)Rb PET is its capacity to accurately quantify MBF. Quite importantly, it has been recently shown that coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity. Moreover, coronary flow reserve is a functional parameter particularly useful in the estimate of microvascular dysfunction, such as in diabetes mellitus. Due to the very short half-life of rubidium-82, the effective dose calculated for a rest/stress test is roughly equivalent to the annual natural exposure and even less when stress-only is performed with a low activity compatible with a good image quality with the last generation 3D PET scanners. There is still some debate on the relative advantages of (82)Rb PET with regard to (99m)Tc-SPECT. For the last 10 years, great technological advances substantially improved performances of SPECT with its accuracy getting closer to this of (82)Rb/PET. Currently, the main advantages of PET are its capacity to accurately quantify MBF and to deliver a low radiation exposure.


Size-frequency distributions along a latitudinal gradient in Middle Permian fusulinoideans.
Geographic gradients in body size within and among living species are commonly used to identify controls on the long-term evolution of organism size. However, the persistence of these gradients over evolutionary time remains largely unknown because ancient biogeographic variation in organism size is poorly documented. Middle Permian fusulinoidean foraminifera are ideal for investigating the temporal persistence of geographic gradients in organism size because they were diverse and abundant along a broad range of paleo-latitudes during this interval (~275-260 million years ago). In this study, we determined the sizes of Middle Permian fusulinoidean fossils from three different paleo-latitudinal zones in order to examine the relationship between the size of foraminifers and regional environment. We recovered the following results: keriothecal fusulinoideans are substantially larger than nonkeriothecal fusulinoideans; fusulinoideans from the equatorial zone are typically larger than those from the north and south transitional zones; neoschwagerinid specimens within a single species are generally larger in the equatorial zone than those in both transitional zones; and the nonkeriothecal fusulinoideans Staffellidae and Schubertellidae have smaller size in the north transitional zone. Fusulinoidean foraminifers differ from most other marine taxa in exhibiting larger sizes closer to the equator, contrary to Bergmann's rule. Meridional variation in seasonality, water temperature, nutrient availability, and carbonate saturation level are all likely to have favored or enabled larger sizes in equatorial regions. Temporal variation in atmospheric oxygen concentrations have been shown to account for temporal variation in fusulinoidean size during Carboniferous and Permian time, but oxygen availability appears unlikely to explain biogeographic variation in fusulinoidean sizes, because dissolved oxygen concentrations in seawater typically increase away from the equator due to declining seawater temperatures. Consequently, our findings highlight the fact that spatial gradients in organism size are not always controlled by the same factors that govern temporal trends within the same clade.


Right ventricular function in cor pulmonale.
Traditionally the right ventricle has been thought to function poorly in the presence of an increased afterload. Indeed, the presence of pulmonary arterial hypertension, or cor pulmonale, has been associated with a poor prognosis in patients with hypoxic chronic obstructive pulmonary disease (COPD). Recent data suggest that right ventricular contractility as measured by the right ventricular end-systolic pressure/volume relationship is relatively normal in patients with COPD, despite the presence of pulmonary arterial hypertension if the patients are studied when clinically stable, but reduced when the patients present with oedema. Continuous oxygen therapy is the only treatment which has been shown to improve survival in patients with COPD and cor pulmonale. However, the effects of oxygen therapy may not be directly related to an improvement in cardiac function.


Carcinoma of the hypopharynx--a five year follow-up.
This is a study of 339 patients with carcinoma of the hypopharynx, seen in Toronto from 1960-72. Patients were grouped according to the U.I.C.C., T.M.N. classification but a modified staging method was employed since there is no generally accepted procedure for stage-grouping at the present time. Patients treated by primary radiation were compared to a group treated by combined therapy (radiation followed by surgery). The results show that the overall crude survival of all hypopharyngeal lesions was approximately 20 per cent. A high percentage of patients had advanced lesions at first presentation and almost 30 per cent of patients were treated palliatively. Analysis indicated that combined therapy is the treatment choice for Stage I and II hypopharyngeal lesions. Patients with more advanced lesions do poorly regardless of the treatment modality. The morbidity and mortality rates are high in the combined therapy group but the risks were doubled when salvage surgery was undertaken for failed primary radiotherapy.


Infantile chronic subdural hematoma of the posterior fossa diagnosed by computerized tomography. Case report.
A 9-week-old infant manifested continuous vomiting for 1 week accompanied by a tense fontanel, "sun setting" of the eyes, frequent opisthotonos, and hypertonicity. The head circumference was at the 50th percentile. Computerized tomography (CT) revealed acute hydrocephalus and a posterior fossa subdural hematoma. The brain stem and cerebellum were of greater density (54 Hounsfield units) than normal cerebral white matter (42 Hounsfield units) whereas the subdural hematoma was the same density as normal cerebral white matter ("isodense"). The cerebellum and brain stem became enhanced by contrast (68 Hounsfield units), but no enhancement occurred in the cerebral white matter or subdural hematoma. A shunt followed by occipital craniectomy resolved both the hydrocephalus and subdural hematoma. Repeat CT scan 15 days postoperatively disclosed continuing higher density of the cerebellum and brain stem (60 Hounsfield units) relative to cerebral white matter. Increased density of the infantile cerebellum has been noted previously but not to the same extent as in this patient.


Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein.
Circulating antiplasmin-cleaving enzyme (APCE) has a role in fibrinolysis and appears structurally similar to fibroblast activation protein (FAP), a cell-surface proteinase that promotes invasiveness of certain epithelial cancers. To explore this potential relationship, we performed comparative structure/function analyses of the 2 enzymes. APCE from human plasma and recombinant FAP (rFAP) exhibited identical pH optima of 7.5, extinction coefficients (in(280 nm)(1%)) of 20.2 and 20.5, common sequences of tryptic peptides, and cross-reactivity with FAP antibody. APCE and rFAP are homodimers with monomeric subunits of 97 and 93 kDa. Only homodimers appear to have enzymatic activity, with essentially identical kinetics toward Met-alpha2-antiplasmin (Met-alpha2AP) and peptide substrates. APCE and rFAP cleave both Pro3-Leu4 and Pro12-Asn13 bonds of Met-alpha2AP, but relative kcat/Km values for Pro12-Asn13 are about 16-fold higher than for Pro3-Leu4. APCE and rFAP demonstrate higher kcat/Km values toward a peptide modeled on P4-P4' sequence surrounding the Pro12-Asn13 primary cleavage site than for Z-Gly-Pro-AMC and Ala-Pro-AFC substrates. These data support APCE as a soluble derivative of FAP and Met-alpha2AP as its physiologic substrate. Conversion of Met-alpha2AP by membrane or soluble FAP to the more easily fibrin-incorporable form, Asn-alpha2AP, may increase plasmin inhibition within fibrin surrounding certain neoplasms and have an impact on growth and therapeutic susceptibility.


Trends in somatic cell counts, bacterial counts, and antibiotic residue violations in New York State during 1999-2000.
Milk quality data on a month-by-month basis from March 1999 to December 2000 were studied from five of the largest milk plants operating in New York State. The analyses focused on bulk tank somatic cell count (SCC), bacterial counts in the form of plate loop count (PLC), and antibiotic residue violations in the pool of milk of New York State, their mutual relation, and the influence of farm size. The average SCC was 363,000 cells/ml, the average PLC was 24,400 bacteria/ml, and the average number of antibiotic residue violations in the pool of milk was 3.9 per 1000 producers. Each month between 72 and 88% of the milk pool had SCC levels in compliance with the European Union (EU) requirements (SCC < 400,000 cells/ml). The findings in this study suggest that larger farms had lower SCC and PLC but more antibiotic violations. However, the larger farms contribute most to the SCC and PLC of the total pool of milk. Farms with high SCC also had higher PLC and more antibiotic violations. Measurable improvements in overall quality of the pool of milk in New York state would most likely occur by targeting incentives, education, and training programs for any farms with very high SCC and for larger farms with SCC between 400,000 and 750,000 cells/ml.


Endotoxin levels at Swine farms using different waste treatment and management technologies.
Concentrated animal feeding operations (CAFOs) are a major source of airborne endotoxins, which are air pollutants that can cause adverse health effects to both on-site farmers and neighbors. Release of airborne endotoxins to the environment can be reduced using proper waste treatment and management technologies. In this study, the levels of endotoxins released from two swine CAFOs using conventional lagoon-sprayfield technology were compared to those of 15 farms using various alternative waste management technologies in North Carolina. Over a 2-year period, 236 endotoxin samples were collected from the 17 farm units and analyzed using the Limulus amebocyte lysate (LAL) test. Concentrations of airborne endotoxins near barn exhaust fans were significantly higher than at the upwind boundary of the farm and at other farm sites. For most of the study sites, mean concentrations of endotoxins at the downwind boundary of the farm were higher than those at the upwind boundary of the farm, indicating the release of endotoxins from swine CAFOs to the neighboring environment. Endotoxin levels were significantly associated with concentrations of airborne bacteria but not fungi. Environmental factors, such as temperature, relative humidity, and wind velocity, affected the levels of airborne endotoxins at the farms. Based on the ratios of airborne endotoxins in downwind and upwind samples from the farm units, at least five different alternative waste management technologies significantly reduced the release of endotoxins from swine CAFOs. These results suggest that swine CAFOs are important sources of airborne endotoxins, the levels of which can be reduced by applying more robust and effective waste management technologies.


[Atypical presentation of intramedullary sarcoidosis: report of two cases].
Neurological involvement in sarcoidosis occurs in 5 to 15% of cases, but medullary involvement is very uncommon. We report two cases of sarcoidosis with medullary involvement as an initial presentation. Case 1: a 41 year-old man presented with a four-month history of lumbar pain, gait and sphincter disturbances; examination revealed a spastic paraparesis, hyperreflexia and a sensory level by D4-D6. Serum angiotensin converting enzyme (SACE) was normal. Magnetic resonance image (MRI) showed diffuse spinal cord enlargement with hyperintensity signal between D4-D5 and D10-11, with contrast enhancement. Spinal biopsy was consistent with sarcoidosis. Case 2: a 36 year-old man presented with a two-months history of gait difficulties and two episodes of blurred vision on his left eye that improved with topical therapy. Examination revealed lupus pernio in the ears and a spastic hyperreflexic paraparesis. Laboratory detected increased SACE. MRI showed focal spinal cord areas of hyperintensity at cervico-dorsal levels with contrast enhancement. Ear biopsy was consistent with sarcoidosis. Clinical courses under corticosteroids were favourable in both cases. Intramedullary lesions are infrequently the first manifestation of sarcoidosis especially when there is no systemic involvement (case 1). It is also rare in association with lupus pernio and ocular involvement (case 2). In the later (with systemic manifestations) SACE was raised. Biopsy is very useful for early diagnosis.


The progress and controversies regarding steroid use in acute spinal cord injury.
Acute spinal cord injury (SCI) is a devastating disease that causes immense physical and mental harm to the patient and the family, and society and requires a multidisciplinary approach to treatment. The study of acute SCI has a long history but is still emerging. As the mechanism and pathophysiology of acute SCI are continuously being studied and explored, the treatment of SCI has developed significantly. Steroids are thought to provide neuroprotection in patients with acute SCI by improving perfusion, reducing edema, modulating inflammatory cells, and inhibiting lipid peroxidation, leading to their widespread application in clinical medicine. The use of steroids for SCI is controversial because of limited clinical evidence. With the accumulation of evidence on the effectiveness of steroid treatment in improving neurological function and the evidence of severe side effects, a gradual change in the treatment of SCI with steroids has become inevitable. Most scholars have focused on the routine use of steroids because of the indefinite improvement in neurological function and the occurrence of severe adverse events. Therefore, this review aims to provide an overview of the mechanism, progress, and related controversies to comprehensively understand the value and future direction of steroid application in acute SCI.


Shear wave elastography of the scalene muscles in healthy adults: A preliminary study.
The aim of the study is to evaluate the reliability of shear wave elastography to assess the anterior and middle scalene muscles in healthy adult subjects.The study included 60 scalene muscles in 15 healthy subjects. High-resolution ultrasound and shear wave elastography were used to evaluate the anterior scalene and the middle scalene muscles. Stiffness values were measured.The mean shear elastic modulus showed the following values, right anterior scalene muscle 18.83 ± 5.32 kPa, left anterior scalene muscle 21.71 ± 4.8 kPa, right middle scalene muscle 12.84 ± 5.2 kPa, left middle scalene muscle 19.76 ± 5.30 kPa. Positive correlation was noted between the left middle scalene muscle and body mass index (P = .004). No difference in elasticity was noted between the right and left anterior scalene muscles; however, significant difference was noted between the right and left middle scalene muscles (P = .002).The results obtained in our study could be a reference point for future research considering different scalene muscle pathologies.


Pulmonary arterial hypertension due to antiphospholipid syndrome initially mimicking chronic thromboembolic pulmonary hypertension.
Pulmonary arterial hypertension (PAH) is the second most common lung complication in antiphospholipid syndrome (APS) patients. However, the concurrent development of APS-related nonthrombotic PAH is rarely reported. Lack of awareness for group 1 PAH in APS patient may contribute to underdiagnosis of this condition. Herein, we reviewed the case of a 56-year-old female who was diagnosed with PAH related to APS that mimicked chronic thromboembolic pulmonary hypertension (CTEPH). It is crucial to be aware of the possibility of a group 1 PAH diagnosis, even though patients have already been diagnosed with CTEPH. Furthermore, a multidisciplinary approach and serial follow-up right heart catheterization with echocardiography are important to make a timely diagnosis and provide optimal treatment for APS-related PAH in patients with CTEPH-like clinical features.


Manumycin A inhibits triple-negative breast cancer growth through LC3-mediated cytoplasmic vacuolation death.
Therapy resistance can be attributed to acquisition of anti-apoptotic mechanisms by the cancer cells. Therefore, developing approaches that trigger non-apoptotic cell death in cancer cells to compensate for apoptosis resistance will help to treat cancer effectively. Triple-negative breast cancers (TNBC) are among the most aggressive and therapy resistant to breast tumors. Here we report that manumycin A (Man A), an inhibitor of farnesyl protein transferase, reduces cancer cell viability through induction of non-apoptotic, non-autophagic cytoplasmic vacuolation death in TNBC cells. Man A persistently induced cytoplasmic vacuolation and cell death through the expression of microtubule-associated protein 1 light chain 3 (LC3) and p62 proteins along with endoplasmic reticulum (ER) stress markers, Bip and CHOP, and accumulation of ubiquitinated proteins. As inhibitors of apoptosis and autophagy failed to block cytoplasmic vacuolation and its associated protein expression or cell death, it appears that these processes are not involved in the death induced by Man A. Ability of thiol antioxidant, NAC in blocking Man A-induced vacuolation, death and its related protein expression suggests that sulfhydryl homeostasis may be the target of Man A. Surprisingly, normal human mammary epithelial cells failed to undergo cytoplasmic vacuolation and cell death, and grew normally in presence of Man A. In conjunction with its in vitro effects, Man A also reduced tumor burden in vivo in xenograft models that showed extensive cytoplasmic vacuoles and condensed nuclei with remarkable increase in the vacuolation-associated protein expression together with increase of p21, p27, PTEN and decrease of pAkt. Interestingly, Man A-mediated upregulation of p21, p27 and PTEN and downregulation of pAkt and tumor growth suppression were also mimicked by LC3 knockdown in MDA-MB-231 cells. Overall, these results suggest novel therapeutic actions by Man A through the induction of non-apoptotic and non-autophagic cytoplasmic vacuolation death by probably affecting ER stress, LC3 and p62 pathways in TNBC but not in normal mammary epithelial cells.


[In-stent thrombosis following coronary artery by-pass grafting - a case report].
A case of a 60 year old male with a history of myocardial infarction treated with coronary angioplasty with stent implantation, who was admitted to the hospital for coronary artery by-pass grafting (CABG), is presented. The post-operative course was complicated by new acute MI due to the in-stent thrombosis. The patient received aspirin and ticlopidine, and underwent intra-aortic balloon pumping followed-by an effective coronary angioplasty of the infarct-related coronary artery.


Göteborg Metoprolol Trial: design, patient characteristics and conduct.
The Göteborg Metoprolol Trial was a double-blind, placebo-controlled, stratified trial aimed at evaluating the effect of the beta 1-selective blocker, metoprolol, in suspected acute myocardial infarction and during 2 years of follow-up. The primary end-point was 3-month mortality (blind treatment period). Secondary end-points were 2-year mortality, indirect signs of infarct size, chest pain, arrhythmias and tolerability. The entry criteria were fulfilled in 2,802 patients, 1,395 of whom were included in the trial. Treatment started as soon as possible after arrival in hospital with intravenous administration followed by oral treatment for 3 months. All patients were randomized 48 hours or less after estimated onset of infarction and 69% were randomized at 12 hours or less. The blind treatment had to be withdrawn in 19% of all randomized patients before the end of the 3-month follow-up.


Characterization of monocyte maturation in adherent and suspension cultures and its application to study monocyte differentiation in Hodgkin's disease.
Monocytes purified with cell scatter monitored counterflow centrifugation were cultured in plastic (adherent) and in teflon culture bags (suspension). Sequential changes were monitored during 15 days by measuring intracellular activity of three enzymes of intermediary metabolism: glucose-6-phosphate dehydrogenase (G-6-PDH), phosphohexose isomerase (PHI) and isocitrate dehydrogenase (ICDH), and the two acid hydrolases: acid phosphatase (ACP) and N-acetyl-beta-glucosaminidase (NAG). In teflon grown macrophages a significantly lower G-6-PDH activity was seen after 15 days in comparison to plastic adherent macrophages (P less than 0.0002). For the other enzymes similar values for both culture modalities were found. The significantly, cycloheximide insensitive, higher values for G-6-PDH, PHI and ICDH in 2 h plastic adherent monocytes in comparison with plastic non-adherent monocytes, suggest a relationship between adherent capacity and the level of intermediary metabolism. The overall yield of plastic adherent macrophages after 15 days was 35% in contrast with 89% for the in suspension cultured macrophages. This corroborates the existence of adherent and non-adherent monocytes, both capable of differentiation in vitro. In 14 patients with advanced Hodgkin's disease (HD) and 14 normal controls, monocyte differentiation was studied applying both culture modalities. The enzyme levels, reflecting growth and intermediary metabolism, were similar for both groups. The adherent capacity and yield, both in teflon and in plastic, after 15 days was comparable for both groups. It was concluded that in vitro monocyte differentiation in the presence of autologous serum was qualitatively and quantitatively normal in advanced HD; this is in favour of an intrinsically normal function of monocytes in HD.


Clinical and ultrasonographical follow-up after standard removal of distal radius volar plates positioned distal to the watershed line.
Marginal fracture types of the distal radius may require volar plate positioning distal to the watershed line. Subsequently, plate prominence with direct friction with the flexor tendons occurs which is associated with flexor tendon pathology. Standard plate removal can be proposed. This cohort study examined clinical outcome, patient satisfaction and ultrasonographical assessment of the relation of the flexor pollicis longus (FPL) and the volar rim after standard plate removal. Twenty patients with volar plate prominence after osteosynthesis for distal radius fractures were included. Plate removal was performed at least 4 months after initial surgery. The mean age was 60 years (range 39-84). The average delay from hardware removal to assessment was 2.9 years (range 1.0-5.0 years). Mean flexion, extension and radial deviation were significantly decreased (p < 0.05) compared to the contralateral side, while ulnar deviation, pro- and supination and grip strength were not. Mean QuickDASH score was 21.5. 85% of patients described their result as good to excellent. 80% would undergo the intervention again. During ultrasonography, distance from FPL to volar rim remained significantly decreased compared to the uninjured side in neutral and flexed position (p < 0.05) despite plate removal. The largest distance between the FPL and the volar cortical bone, which is mainly occupied by the pronator quadratus, did not differ. In this study, the range of motion and FPL distance to the distal radius normalized only partially compared to the uninjured wrist after standard plate removal.


Incidence and predictors of pacemaker-induced cardiomyopathy with right ventricular pacing: a systematic review.
This systematic review aims to evaluate the incidence and predictors of pacemaker-induced cardiomyopathy (PICM) in patients undergoing right ventricular pacing. A literature review was conducted using MeSH terms (Right ventricular pacing, Pacemaker-related cardiomyopathy, Pacemaker-induced cardiomyopathy) in PubMed, EMBASE, Web of science CINAHL, and the Cochrane Library until October 2021. All data reporting the incidence of PICM after implantation of right-sided pacemakers or implantable cardioverter-defibrillator (ICD) were retrieved from the eligible studies. Out of 3,625 articles, 20 studies met the inclusion criteria that included 5,381 patients. . The mean age of the patients ranged between 55.8 ± 13.5 and 77.4 ± 10.8 years. The mean incidence of PICM was 25.7%. Mean ejection fraction (EF) at baseline ranged from 48 ± 1% and 62.1 ± 11.2%, while mean EF at follow-up ranged between 33.7 ± 7.4% and 53.2 ± 8.2%. Three studies reported a decline of >20% EF at follow-up. RV pacing was associated with a considerable risk of PICM, with biological factors, such as male gender, old age, increased QRS duration, and chronic RV pacing burden playing an important role in the development of disease.


Transcriptome analysis of yellow catfish (Pelteobagrus fulvidraco) liver challenged with polyriboinosinic polyribocytidylic acid (poly I:C).
Yellow catfish (Pelteobagrus fulvidraco) is one of the most important economic freshwater species in China. However, infection by bacterial pathogenic diseases has caused high mortality and great economic loss in aquaculture. It is necessary for disease control to know more about the P. fulvidraco immune system and its related genes in response to bacterial or viral infections. In this study, the transcriptomic profiles of liver from P. fulvidraco stimulated by polyriboinosinic polyribocytidylic acid (poly I:C) was analyzed using high-throughput sequencing method. After assembly and annotation, total 67,447 unigenes were acquired, with an average length of 1091 bp. Under the infection of poly I:C, 522 differentially expressed genes (DEGs) were identified, including 307 up-regulated genes and 215 down-regulated genes. To further investigate the immune-related DEGs, Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed. The result of GO enrichment indicated gene response to external stimulus, regulation of response to stimulus, cellular response to stimulus, immune response and immune system progress. Significant KEGG enrichment analysis identified major immune related pathways. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that 13 immune response genes were identified to be up-regulated after 12 h of poly I:C stimulation compared to controls. Taken together, the results of our study are beneficial for better understanding of the immune system and defense mechanisms of yellow catfish in response to poly I:C infection.


Villin immunohistochemistry is a reliable method for diagnosing microvillus inclusion disease.
Microvillus inclusion disease (MVID) is a rare congenital disorder that manifests early in infancy as intractable watery diarrhea. The entity is characterized morphologically by a deficient brush border and apical cytoplasmic inclusions within absorptive cells (enterocytes) due to misplaced assembly of brush border proteins. The diagnosis is based upon histopathology, special stains, immunohistochemistry (IHC), and ultimately upon electron microscopy. Currently, the periodic acid-Schiff stain (PAS) and CD10 IHC are commonly used as adjuncts, but in addition to brush border structures, they stain a variety of apical cytoplasmic inclusions and organelles, thereby interfering with recognition of microvillus inclusions. Villin is a protein that specifically binds to the actin core bundle of microvilli. We utilized villin IHC in formalin-fixed paraffin-embedded gastrointestinal biopsies from 6 patients with MVID, 5 with celiac disease, and 17 children with normal intestinal biopsies and compared the results with those obtained with CD10 IHC and PAS staining. All MVID cases had confirmatory electron microscopy at the time of diagnosis. Villin immunoreactivity was restricted to the brush border in the control groups. In MVID, villin IHC showed attenuation or loss of the surface brush border and also highlighted the cytoplasmic microvillus inclusions with clarity. In MVID, CD10 IHC and the PAS stain also showed attenuation or loss of the surface brush border, but staining of a variety of cytoplasmic structures largely obscured the microvillus inclusions. In sum, villin IHC is a reliable and superior adjunct in the diagnosis of MVID. Study of additional cases will determine whether villin IHC would obviate the need for electron microscopic confirmation.


Summary Report of the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society's Symposium on Targets for Osteoarthritis Research: Part 1: Epidemiology, Pathophysiology, and Current Imaging Approaches.
This first of a 2-part series of articles recounts the key points presented in a collaborative symposium sponsored jointly by the Arthritis Foundation and the American Orthopaedic Foot & Ankle Society with the intent to survey the state of scientific knowledge related to incidence, diagnosis, pathologic mechanisms, and injection treatment options for osteoarthritis (OA) of the foot and ankle. A meeting was held virtually on December 3, 2021. A group of experts were invited to present brief synopses of the current state of knowledge and research in this area. Part 1 overviews areas of epidemiology and pathophysiology, current approaches in imaging, diagnostic and therapeutic injections, and genetics. Opportunities for future research are discussed. The OA scientific community, including funding agencies, academia, industry, and regulatory agencies, must recognize the needs of patients that suffer from arthritis of foot and ankle. The foot and ankle contain a myriad of interrelated joints and tissues that together provide a critical functionality. When this functionality is compromised by OA, significant disability results, yet the foot and ankle are generally understudied by the research community. Level of Evidence: Level V - Review Article/Expert Opinion.


The c-myc proto-oncogene regulates cardiac development in transgenic mice.
During the maturation of the cardiac myocyte, a transition occurs from hyperplastic to hypertrophic growth. The factors that control this transition in the developing heart are unknown. Proto-oncogenes such as c-myc have been implicated in the regulation of cellular proliferation and differentiation, and in the heart the switch from myocyte proliferation to terminal differentiation is synchronous with a decrease in c-myc mRNA abundance. To determine whether c-myc can influence myocyte proliferation or differentiation, we examined the in vivo effect of increasing c-myc expression during embryogenesis and of preventing the decrease in c-myc mRNA expression that normally occurs during cardiac development. The model system used was a strain of transgenic mice exhibiting constitutive expression of c-myc mRNA in cardiac myocytes throughout development. In these transgenic mice, increased c-myc mRNA expression was found to be associated with both atrial and ventricular enlargement. This increase in cardiac mass was secondary to myocyte hyperplasia, with the transgenic hearts containing more than twice as many myocytes as did nontransgenic hearts. The results suggest that in the transgenic animals there is additional hyperplastic growth during fetal development. However, this additional proliferative growth is not reflected in abnormal myocyte maturation, as assessed by the expression of the cardiac and skeletal isoforms of alpha-actin. The results of this study indicate that constitutive expression of c-myc mRNA in the heart during development results in enhanced hyperplastic growth and suggest a regulatory role for this proto-oncogene in cardiac myogenesis.


Helicobacter pylori and associated histopathological changes in gastric biopsies of patients with leprosy.
Two antral biopsies each from 104 patients of leprosy and 100 controls were studied to find out the prevalence of H. pylori and associated histopathological changes. Sections were stained with hematoxylene and eosin, AB/PAS (Ph 2.5) and Loeffler's methylene blue stains. Infection by H. pylori, inflammation and atrophy were found to be significantly more in leprosy patients as compared to controls (p < 0.01, < 0.005 and < 0.02 respectively). On comparing the histopathological changes in various subgroups of leprosy, H. pylori, inflammation and activity showed a statistically decreasing trend from tuberculoid to lepromatous subgroups (p < 0.05, < 0.001, < 0.01 respectively). Atrophy showed a significant increasing trend from tuberculoid to lepromatous group (< 0.001), it is concluded that despite a low prevalence of H. pylori and associated gastritis in patients with lepromatous leprosy, gastric epithelial damage is more marked due to altered immune response.


Evaluation of postcraniotomy patients by radionuclide scan.
Twenty-eight patients with cerebral tumors were evaluated after craniotomy with combined radionuclide techniques in order to assess presence or absence of tumor recurrence. The combination of a positive pertechnetate or Tc-phosphate scan with a positive gallium scan strongly indicates the presence of recurrent or residual tumor. Infection may also cause uptake but was easily distinguished by the distribution. Negative gallium scans with positive technetium scans were indicative of non-recurrence in this series.


[Neuromyelitis optica spectrum disorder and pregnancy].
Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune inflammatory diseases of the central nervous system that mainly affect women. In some of these patients NMOSD occurs during fertile age. For this reason, treating physicians may be confronted with questions concerning family planning, pregnancy and birth. This study provides an overview on the influence of NMOSD on fertility, pregnancy complications and pregnancy outcome. The effect of pregnancy on NMOSD course and therapy options during pregnancy are discussed. A search of the current literature was carried out using the PubMed database. Animal studies have shown lower fertility rates in NMOSD; however, studies investigating fertility in NMOSD patients are lacking. Pregnancy in NMOSD patients are associated with an increase in postpartum disease activity and a higher grade of disability after pregnancy. Some studies showed higher risks of pregnancy complications e. g. spontaneous abortions and preeclampsia. With a few limitations, acute relapses during pregnancy can be treated with methylprednisolone and/or plasma exchange/immunoadsorption. Stopping or continuing immunosuppressive therapy with azathioprine or rituximab during pregnancy should be critically weighed considering previous and current disease activity. Therefore, a joint supervision by a specialized center is recommended, particularly in specific situations such as pregnancy.


Bilateral mycotic cerebral abscess due to aspergillosis--a case report.
Aspergillosis of central nervous system is an uncommon infection mainly occurring in immunocompromised patient. It may be present in several forms: abscess, meningitis, mycotic aneurysm, infarction and in tumoral form. Here we report a case of cerebral aspergillosis presenting as bilateral frontal lobe abscess without evidence of any underlying systemic disorder or extracranial disease.


Upper extremity physeal injury in young baseball pitchers.
Adolescent baseball players, especially pitchers, are at increased risk for shoulder and elbow injuries as their level of competition increases. The intersection of the adolescent growth spurt with the high levels of elbow valgus and shoulder rotational torques placed upon the arm during overhand pitching predisposes the shoulder and elbow to physeal injuries. Little League shoulder and Little League elbow syndromes most commonly represent pathology at the physeal regions of the proximal and distal humerus and proximal ulna sustained from repetitive loads caused by overhead throwing. There is a growing understanding that these injuries occur on a wide spectrum from delayed physeal closure and physeal widening to acute transphyseal fracture. Although operative intervention is infrequently required, patient and parent counseling can be complex. Health care professionals who care for adolescent baseball players also can play an important role in prevention. Appropriate counseling requires a comprehensive understanding of the clinical, radiographic, and biomechanical aspects of these injuries. This review summarizes these major concepts, focusing on the best available evidence from recent biomechanical and clinical studies on shoulder and elbow injuries in adolescent baseball pitchers.


Genetic screening of FecB, FecXG and FecXI mutations and their linkage with litter size in Barki and Rahmani sheep breeds.
Characterization of fecundity genes offers the opportunity to improve production efficiency, and the consequent increase in litter size in livestock industry, through utilizing them in breeding programs. The main objective of this study was to detect the BMPR-IB, BMP15 and GDF9 gene mutations and to investigate whether these mutations are associated with litter size in Egyptian sheep breeds. To achieve this goal, 73 adult ewes representing Barki (n = 33) and Rahmani (n = 40) breeds were used. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) screening approach was used to detect the presence of FecB, FecXG and FecXI mutations in the two selected breeds. Results of this study showed that the three different candidate gene mutations, namely FecB, FecXG and FecXI are not present among these selected populations of the Egyptian breeds. Further studies regarding other mutations and/or other genes, which may influence ovulation rate, should be carried out to determine the type and mode of inheritance of such genes in Egyptian sheep breeds.


Kinetic Resolution of sec-Thiols by Enantioselective Oxidation with Rationally Engineered 5-(Hydroxymethyl)furfural Oxidase.
Various flavoprotein oxidases were recently shown to oxidize primary thiols. Herein, this reactivity is extended to sec-thiols by using structure-guided engineering of 5-(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of racemic sec-thiols, thus yielding the corresponding thioketones and nonreacted R-configured thiols with excellent enantioselectivities (E≥200). The engineering strategy applied went beyond the classic approach of replacing bulky amino acid residues with smaller ones, as the active site was additionally enlarged by a newly introduced Thr residue. This residue established a hydrogen-bonding interaction with the substrates, as verified in the crystal structure of the variant. These strategies unlocked HMFO variants for the enantioselective oxidation of a range of sec-thiols.


Colonic intussusception masquerading as diverticulitis: a case report of a 31 year old diagnosed with colorectal carcinoma after multiple presentations to the ED for episodes of acute diverticulitis.
Colonic intussusception is a rare occurrence in adults, with few reported cases in the literature. Patients often present with nonspecific and vague symptoms leading to diagnostic challenges and delayed treatment. Given the high incidence of underlying malignancy associated with cases of adult intussusception, it is important for clinicians to be able to recognize and coordinate appropriate follow-up. A 31-year-old female presented to the emergency department four times over a month with left lower quadrant abdominal pain. Multiple computed tomography scans showed inflammation and diverticulitis of the mid-descending colon along with a short segment of colonic intussusception. A colonoscopy was performed due to concern for malignancy. A partially obstructing mass was found in the descending colon that could not be traversed. Biopsies revealed necrosis and no evidence of malignancy. However, given high suspicion for malignancy, the patient underwent a laparoscopic left colectomy, which revealed a pT3N1b colon adenocarcinoma.


Pharmacological studies of the two new hypoglycaemic compounds 4-(3-methyl-5-oxo-2-pyrazolin-1-yl)benzoic acid and 1-(mesitylen-2-sulfonyl)-1H-1,2,4-triazole.
New compounds showing hypoglycaemic activity have been designed through a computer-aided method based on QSAR (quantitative structure activity relationship) and molecular connectivity. The pharmacological tests carried out on the newly designed compounds demonstrated the existence of notable activity for two of them, namely: 4-(3-methyl-5-oxo-2-pyrazolin-1-yl) benzoic acid (CAS 60875-16-3) and 1-(mesitylen-2-sulfonyl)-1H-1,2,4-triazole, (CAS 54230-59-0). Both substances mainly follow a mechanism based on the response to the oral glucose overcharge, decreasing the glycemia to lower levels as compared with tolbutamide, which is used as a standard drug, and reaching normal glycaemia at a similar time.


Linguistic performance in vulnerable and autistic children and their mothers.
The authors studied the language patterns of schizophrenic mothers and their 4-year-old children, and compared them with the speech of normal mothers and children and normal mothers with autistic children. They found that children of schizophrenic mothers showed lags in language development and language distortions less severe than but in some ways similar to those seen in autistic children. Schizophrenic mothers were more likely to produce more deficient and/or distorted language in interactions with their children. Mothers of autistic children produced language that was equal to or above that of mothers of normal children on most parameters and adjusted their language to the chronological rather than the linguistic age of the child.


Penile prosthesis: patient teaching and perioperative care.
As more options become available for treating erectile dysfunction (ED), more men are seeking treatment. Despite excellent efficacy of available medical management, a percentage of these patients will be refractory to the less invasive options for treatment, leaving the surgical implantation of a penile prosthesis as their remaining option for definitive treatment of ED. The patient seeking penile prosthesis surgery faces many challenges as he proceeds through the perioperative processes. A thorough understanding of indications, preoperative assessment and teaching, intraoperative procedure, and postoperative care and teaching for the patient receiving a penile prosthesis will enable him to achieve the best possible outcome.


Effects of increased heart work on release of norepinephrine and ventricular arrhythmias following reperfusion in the isolated rat heart.
The influence of increasing left atrial pressures (0.5, 1.0, and 2.0 kPa) on the incidence of ventricular arrhythmias and the liberation of prelabeled norepinephrine (3H-NE) was investigated in the isolated working rat heart. Acute regional myocardial ischemia (30 min) was produced by ligature of the left main coronary artery with subsequent release of the ligature to achieve reperfusion, which consistently provoked ventricular arrhythmias. The magnitude of regional ischemia was measured by microspheres, and the efflux of 3H-labeled NE compounds was measured in the coronary effluent. Our data show that an increase in atrial pressure enhanced reperfusion arrhythmias, but the magnitude of NE release was not directly related to the occurrence of arrhythmias. It is proposed that increased heart work has an arrhythmogenic effect by enhancing the severity of regional ischemia.


Improved bioavailability and pharmacokinetics of tea polyphenols by encapsulation into gelatin nanoparticles.
The authors prepared surface modified (with polyelectrolyte layers), tea polyphenols (TPP) encapsulated, gelatin nanoparticles (TPP-GNP) and characterised them. The size of the spherical nanoparticles was ∼50 nm. Number of polyelectrolyte layers and incubation time influenced the encapsulation efficiency (EE); highest EE was noted in nanoparticles with six polyelectrolyte layers (TPP-GNP-6L) incubated for 4 h. TPP released from TPP-GNP-6L in simulated biological fluids indicated protection and controlled release of TPP due to encapsulation. Mathematical modelling indicated anomalous type as a predominant mode of TPP release. TPP-GNP-6L exhibited enhanced pharmacokinetics in rabbit model compared with free TPP. The area under the concentration-time curve and mean residence time were significantly higher in TPP-GNP-6L compared with free TPP which provide an evidence of higher bioavailability of TPP due to encapsulation. The authors demonstrated that encapsulation of TPP into GNPs favoured slow and sustained release of TPP with improved pharmacokinetics and bioavailability thereby can prolong the action of TPP.


[Preoperative and postoperative lengths of extrahepatic biliary duct measured by direct cholangiography].
The lengths of extrahepatic duct of 110 cases of cholecystolithiasis and 108 cases of choledocholithiasis were compared by direct cholangiography. An average length of the former was 11.0 +/- 1.45 cm, while that of the latter was 12.5 +/- 1.50 cm. There was remarkable change in length between cholecystolithiasis and choledocholithiasis. The length of 75 postoperative choledocholithiasis was 10.4 +/- 1.06 cm. The postoperative length of extrahepatic duct of choledocholithiasis was shorten significantly. There was no significant postoperative change in length in cholecystolithiasis and post-operative significantly. There was no significant postoperative change in length in choledocholithiasis. Because almost same length as that of cholecystolithiasis. As for the location of duodenal entry of the choledochus, there was no remarkable difference between cholecystolithiasis group and choledocholithiasis group. Remarkable difference of the length of extrahepatic duct between cholecystolithiasis group and choledocholithiasis group was not observed after surgery. These data suggested that the length of the extrahepatic bile duct is not the cause of stone formation, but the result of choledocholithiasis.


Depth from motion parallax: Deictic consistency, eye contact, and a serious problem with Zoom.
The dynamics of head and eye gaze between two or more individuals displayed during verbal and nonverbal face-to-face communication contains a wealth of information and is used for both volitionary and unconscious signaling. Current video communication systems convey visual signals about gaze behavior and other directional cues, but the information they carry is often spurious and potentially misleading. I discuss the consequences of this situation, identify the source of the problem as a more general lack of deictic consistency, and demonstrate that using display technologies that simulate motion parallax are both necessary and sufficient to alleviate it. I then devise an avatar-based remote communication solution that achieves deictic consistency and provides natural, dynamic eye contact for computer-mediated audiovisual communication.