A preliminary study of shear-wave elastography for the evaluation of varicocele in adolescents and young adults.
The purpose of this study was to use shear-wave elastography (SWE) to assess testicular stiffness changes during the Valsalva maneuver in adolescents and young adults with varicocele, to compare these changes according to clinical severity, and to evaluate the role of SWE in the diagnosis of varicocele. This study included patients undergoing testicular ultrasonography for the diagnosis of varicocele or for post-varicocelectomy follow-up between June 2016 and February 2017. Fifty-four testicles of 27 consecutive patients (mean age, 15.9 years) were classified by clinical grade (grade 0-3). Using SWE, mean testicular stiffness (Emean) was measured at rest and during the Valsalva maneuver. The correlations between multiple ultrasonographic parameters (volume asymmetry, Emean at rest, and absolute and percentage changes in Emean during the Valsalva maneuver) and clinical grade were assessed using the Spearman correlation test. The Emean at rest was similar across clinical grades. During the Valsalva maneuver, increased testicular stiffness was frequently observed in patients with grade 2 or 3 varicocele but rarely observed in those with grade 0 or 1 varicocele. The changes in Emean were positively correlated with the clinical grade (all P<0.001), whereas the Emean at rest and volume asymmetry were not (all P>0.05). A transient, reversible increase in testicular stiffness during the Valsalva maneuver was observed in adolescents with high-grade varicocele, and the degree of stiffness change was correlated with the clinical grade. Stiffness change identified using SWE during the Valsalva maneuver is a potential surrogate indicator of venous congestion.


Facile one-pot synthesis of MoS2 quantum dots-graphene-TiO2 composites for highly enhanced photocatalytic properties.
We reported a simple one-pot solvothermal approach to fabricate a MoS2 quantum dots (QDs)-graphene-TiO2 (MGT) composite photocatalyst with significantly improved photocatalysis properties, which is caused by the increased charge separation, visible-light absorbance, specific surface area and reaction sites upon the introduction of MoS2 QDs.


Effect of Dexmedetomidine in children undergoing general anaesthesia with sevoflurane: a meta-analysis and systematic review.
The sedative effects of dexmedetomidine (Dex) are similar to natural sleep, with easy wakening following Dex administration, and Dex has minor effects on breathing, reducing emergence agitation in children. The aim of this study was to systematically evaluate the effects of Dex on recovery quality in children following general anaesthesia with sevoflurane, to aid clinical decision making. Relevant randomized controlled trials published before August 2019 were searched and selected from databases. Two researchers independently screened the literature, extracted data, and assessed included studies for bias risk. Meta-analysis was performed using Stata 14.0 software. The study included 24 publications. Following general anaesthesia by sevoflurane, Dex was associated with reduced occurrence of emergence agitation (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.11, 0.25) and nausea and vomiting (OR 0.40, 95% CI 0.24, 0.60), along with shortened eye-opening time (standardized mean difference [SMD] 0.72, 95% CI 0.41, 1.03), shortened extubation time (SMD 0.54, 95% CI 0.28, 0.81), and reduced duration of post-anaesthesia care unit (PACU) stay (SMD 0.29, 95% CI 0.08, 0.51) versus placebo. Dexmedetomidine has positive effects on recovery quality in children undergoing general anaesthesia with sevoflurane.


Double-blind comparison of levocabastine nasal spray with sodium cromoglycate nasal spray in the treatment of seasonal allergic rhinitis.
Nasal levocabastine (0.5 mg/mL) was evaluated for efficacy and tolerance against sodium cromoglycate (20 mg/mL) in a 2-week double-blind trial in 27 and 29 patients with seasonal allergic rhinitis. Globally at 2 weeks, the investigators found a 74% response rate in the levocabastine patients versus a 50% response rate in the cromoglycate patients (P less than .10). Sneezing responded better to levocabastine than to cromoglycate according to three efficacy indicators derived from patient diary ratings of symptom severity: sum of severity scores over the total treatment period as a percentage of the theoretical maximum sum of severity scores (median: 19% versus 41%, P = .01); percentage of symptom-free days (median: 46% versus 22%, P less than .07); percentage of days with moderate or severe symptoms (median: 0% versus 29%, P = .004). Further, the percentage of days with moderate or severe runny nose was lower than in cromoglycate patients (median: 0% versus 25%, P = .09). Although no significant differences were found for itchy nose, blocked nose, and ocular symptoms, severities tended to be generally less under levocabastine than under sodium cromoglycate. Adverse experiences were low level and of similar incidence in the two groups. It is concluded that in a q.i.d. schedule, levocabastine nasal spray is more efficacious than sodium cromoglycate in relieving sneezing and that it is equally well tolerated.


Comparisons of Psycho-Behavioral Factors, Body Composition, and Clinical Outcomes in Adults With Type 2 Diabetes by Perceived Hypoglycemia.
The purpose of the study was to examine the associations between perceived hypoglycemia and psycho-behavioral and clinical factors in persons with type 2 diabetes (T2D). Adults with T2D were recruited from outpatient clinics in a university hospital in Korea. Sociodemographics, psycho-behavioral and clinical factors, and body composition were assessed. The participants were divided into 2 groups reporting perceived hypoglycemia or not in the previous month based on an item of the Control Problem Scale. Group differences were compared at α = .05 using SPSS (version 26.0). Of 177 participants, approximately one-third (n = 67) perceived hypoglycemia. The hypoglycemia group reported poor health-related quality of life, frequent blood monitoring and foot care, and sleep difficulties. However, no differences between groups were identified for diet, exercise, or glycosylated hemoglobin. The hypoglycemia group had a lower body mass index and a trend toward a lower skeletal muscle mass and fat free mass. Perceived hypoglycemia was associated with psycho-behavioral factors and body composition. Importantly, some persons on oral antidiabetic medications that do not cause hypoglycemia still perceived hypoglycemia. Further investigation is warranted to examine the efficacy of strategies to minimize hypoglycemia and inappropriate fear of hypoglycemia. In addition, clinicians should be aware of the potential risk of hypoglycemia in persons with lower muscle mass.


[Intracranial mixed germ cell tumor].
Objective: To study intracranial mixed germ cell tumor diagnosis and reasonable treatment strategy. Methods: Clinical data of 17 patients with intracranial mixed germ cell tumor in Tsinghua university Yuquan hospital from October 2012 to October 2016 were retrospective analysed, including the characteristics of the general, the serum tumor markers of AFP, β-HCG, and CEA, imaging findings, pathological results, treatment methods and prognosis. Results: There were 10 cases of male, 7 cases of female. The average age was (11.1±5.2) years old. Nine cases were gross total resection of lesions and 8 cases were subtotal resection of lesions. Eight cases (47.1%) were without recurrence and had more than four courses of chemotherapy after surgery, of which, 7 cases belonged to the gross total resection, and 1 case belonged to the subtotal resection. Nine (52.9%) patients relapsed, including 2 cases of the gross total resection and 7 cases of the subtotal resection. Among them, 4 cases were given second operations and 6 cases obtained satisfactory therapeutic effect by chemotherapy combined radiotherapy. There were 12 of 17 patients with pathological types contain teratoma (including mature, immature or malignant teratoma) ingredients, accounting for 70.6%. The average follow-up time was (17.5±12.1) months, 4 cases (23.5%) patients died. Conclusion: The diagnosis of intracranial mixed germ cell tumors needs comprehensive consideration of tumor markers in serum or cerebrospinal fluid, chemotherapy and radiotherapy before operation and pathological results. The gross total resection helps to reduce the chances of tumor recurrence. Rational chemotherapy and radiotherapy is helpful to prognosis.


Sodium cholate aggregation and chiral recognition of the probe molecule (R,S)-1,1'-binaphthyl-2,2'-diylhydrogenphosphate (BNDHP) observed by 1H and 31P NMR spectroscopy.
Bile salt micelles can be employed as a pseudostationary phase in micellar electrokinetic capillary chromatography (MEKC) separations of chiral analytes. To improve MEKC separations of chiral analytes, a molecular level understanding of micelle aggregation in the presence of analyte is needed. Here, aggregation of sodium cholate has been observed by exploiting the presence of a model analyte molecule. The 31P and 1H nuclear magnetic resonance spectroscopy (NMR) chemical shifts of (R,S)-1,1'-binaphthyl-2,2'-diylhydrogenphosphate ((R,S)-BNDHP), a model analyte in chiral MEKC separations, are demonstrated to be very sensitive to the aggregation state of the bile salt sodium cholate. In addition to probing micellar aggregation, the NMR spectral resolution of enantiomeric species is also stronglycorrelated with chiral separations in MEKC. In this work, the aggregation of sodium cholate in basic solutions (pH 12) has been observed over the concentration range 0-100 mM. The primary critical micelle concentration (cmc) was found to be 14 +/- 1 mM for basic solutions of sodium cholate. In addition, a primitive aggregate is clearly observed to form at 7 +/- 1 mM sodium cholate. The data also show pseudo-cmc behavior for secondary aggregation observed in the regime of 50-60 mM cholate. Finally, the H5-H7 edge of BNDHP is shown to be sensitive to chirally selective interactions with primary cholate micelles.


Crystal structure of soluble domain of malaria sporozoite protein UIS3 in complex with lipid.
Malaria parasite UIS3 (up-regulated in infective sporozoites gene 3) is essential for sporozoite development in infected hepatocytes. UIS3 encodes for a membrane protein that is localized to the parasite parasitophorous vacuolar membrane in infected hepatocytes. We describe here 2.5-A resolution crystal structure of Plasmodium falciparum UIS3 soluble domain (PfUIS3(130-229)) in complex with the lipid phosphatidylethanolamine (PE). PfUIS3(130-229) is a novel, compact, and all alpha-helical structure bound to one molecule of PE. The PfUIS3(130-229)-PE complex structure reveals a novel binding site with specific interactions between PfUIS3(130-229) and the PE head group. One acyl chain of PE wraps around part of PfUIS3(130-229) and docks onto a hydrophobic channel. We additionally provide new structural and biochemical evidence of PfUIS3(130-229) interactions with lipids (phosphatidylethanolamine), with phospholipid liposomes, and with the human liver fatty acid-binding protein. The direct interaction of PfUIS3(130-229) with liver fatty acid-binding protein most likely provides the parasite with a conduit for importing essential fatty acids/lipids. Therefore, our analyses have implications for lipid transport into the parasite during the rapid growth phases of sporozoites. Given that PfUIS3 is essential for establishment of liver stage infection by P. falciparum, our data provide a new target for abrogating parasite development within liver cells before typical symptoms of malaria can manifest.


The relationship between hopelessness level and complementary and alternative medicine use in patients with breast cancer.
Following the diagnosis and treatment of breast cancer, women may experience some emotions such as anxiety, uncertainty, andhopelessness, and these experiences may vary from person to person. Many patients, along with conventional treatments, can resort to traditional methods to support the treatment, prevent recurrence of cancer, cope with the side effects of the treatment, and strengthen physically and mentally. The study was aimed at determining the relationship between hopelessness level and use of complementary and alternative medicine (CAM) methods in women with breast cancer. In this descriptive and cross-sectional study, 336 women with breast cancer who presented to the mammography unit were contacted. Among the CAM methods used, herbal treatment methods rank first. Of the reasons, women prefer these methods; "CAM provides psychological comfort" takes the first place. The mean scores obtained from the Beck Hopelessness Scale by the women who used and who did not use CAM were 5.45 ± 5.18 and 4.44 ± 4.10, respectively. The difference between the two groups was statistically significant (P < 0.05). In conclusion, women with breast cancer may attempt to use CAM due to hopelessness. Therefore, in the course of medical treatment of patients, CAM practices should be questioned, they should be provided counseling and if necessary, referred for psychological support.


A graphical approach to optimizing variable-kernel smoothing parameters for improved deformable registration of CT and cone beam CT images.
A systematic method is presented for determining optimal parameters in variable-kernel deformable image registration of cone beam CT and CT images, in order to improve accuracy and convergence for potential use in online adaptive radiotherapy. Assessed conditions included the noise constant (symmetric force demons), the kernel reduction rate, the kernel reduction percentage, and the kernel adjustment criteria. Four such parameters were tested in conjunction with reductions of 5, 10, 15, 20, 30, and 40%. Noise constants ranged from 1.0 to 1.9 for pelvic images in ten prostate cancer patients. A total of 516 tests were performed and assessed using the structural similarity index. Registration accuracy was plotted as a function of iteration number and a least-squares regression line was calculated, which implied an average improvement of 0.0236% per iteration. This baseline was used to determine if a given set of parameters under- or over-performed. The most accurate parameters within this range were applied to contoured images. The mean Dice similarity coefficient was calculated for bladder, prostate, and rectum with mean values of 98.26%, 97.58%, and 96.73%, respectively; corresponding to improvements of 2.3%, 9.8%, and 1.2% over previously reported values for the same organ contours. This graphical approach to registration analysis could aid in determining optimal parameters for Demons-based algorithms. It also establishes expectation values for convergence rates and could serve as an indicator of non-physical warping, which often occurred in cases >0.6% from the regression line.


Observations on two strains of plasmodium falciparum from Haiti in Aotus monkeys.
Two strains of Plasmodium falciparum originating in Haiti were studied in the Aotus monkey. The Haitian I/CDC strain was first adapted to in vitro cultivation and subsequently inoculated into monkeys. The Haitian III/CDC strain was inoculated directly from a human patient into the Aotus monkey. The strains varied in their levels of pathogenicity to the animals. The Haitian I/CDC strain was highly virulent in six splenectomized animals; in one intact animal, the infection could be controlled but not eliminated with periodic doses of quinine and chloroquine. After subsequent splenectomy, the animal developed high parasitemias and died. No gametocytes developed in any of the Haitian I infections. The Haitian III strain was lethal to five of the 14 splenectomized monkeys inoculated, but some were able to control their infections without drug intervention. Gametocytes developed in all infections that persisted for an adequate length of time, and infections of mosquitoes were obtained both during the primary attack and the first recrudescence of the parasitemia. Of the mosquitoes tested, Anopheles freeborni was most susceptible to infection, followed by An. culicifacies, An. dirus, An. maculatus, and An. albimanus. The Haitian III strain was successfully transmitted to four other splenectomized Aotus monkeys via sporozoite inoculation using An. freeborni.


Native VOICES: Adapting a video-based sexual health intervention for American Indian teens and young adults using the ADAPT-ITT model.
American Indian and Alaska Native (AI/AN) youth experience disproportionate rates of sexually transmitted infections (STIs). Despite their need for culturally appropriate sexual health interventions, few evidence-based programs have been designed for or rigorously evaluated with AI/AN youth. The primary goal of this study was to adapt a video-based HIV/STI intervention for AI/AN teens and young adults (15-24 years old) living in urban and reservation settings. To capture the heterogeneous experience of AI/AN youth, as well as the viewpoints of adult stakeholders, formative research activities were carried out in collaboration with three geographically dispersed communities in the Pacific Northwest using focus groups and key informant interviews, following the ADAPT-ITT model. Based on participants' feedback, the team produced a culturally tailored intervention toolkit containing a Users Guide, the Native VOICES video, condom and dental dam demonstration videos, and a selection of condoms and dental dams. Forthcoming analyses are evaluating the effectiveness of the Native VOICES intervention with AI/AN youth living across the U.S.


The Role of Hyperthermia in Potentiation of Anti-Angiogenic Effect of Cisplatin and Resveratrol in Mice Bearing Solid Form of Ehrlich Ascites Tumour.
The aim of this study was to investigate the therapeutic potential of resveratrol in combination with cisplatin on the inhibition of tumour angiogenesis, growth, and macrophage polarization in mice bearing the solid form of an Ehrlich ascites tumour (EAT) that were exposed to whole-body hyperthermia treatment. In addition, we investigated whether a multimodal approach with hyperthermia and resveratrol could abolish cisplatin resistance in tumour cells through the modulation of histone deacetylase (HDAC) activity and levels of heat shock proteins (HSP70/HSP90) and contribute to the direct toxicity of cisplatin on tumour cells. The tumour was induced by injecting 1 × 106 EAT cells subcutaneously (sc) into the thighs of Balb/c mice. The mice were treated with resveratrol per os for five consecutive days beginning on day 2 after tumour injection and/or by injecting cisplatin intraperitoneally (ip) at a dose of 2.5 mg/kg on days 10 and 12 and at a dose of 5 mg/kg on day 15. Immediately thereafter, the mice were exposed to systemic hyperthermia for 15 min at a temperature of 41 °C. The obtained results showed that the administration of resveratrol did not significantly contribute to the antitumour effect of cisplatin and hyperthermia, but it partially contributed to the immunomodulatory effect and to the reduction of cisplatin toxicity and to a slight increase in animal survival. This treatment schedule did not affect microvessel density, but it inhibited tumour growth and modulated macrophage polarization to the M1 phenotype. Furthermore, it abolished the resistance of tumour cells to cisplatin by modulating HDAC activity and the concentration of HSP70 and HSP90 chaperones, contributing to the increased lifespan of mice. However, the precise mechanism of the interaction between resveratrol, cisplatin, and hyperthermia needs to be investigated further.


Removal of aflatoxin B1 and inhibition of Aspergillus flavus growth by the use of Lactobacillus plantarum on olives.
Olives can be contaminated with a wide variety of molds (Aspergillus and/or Penicillium) that can be occurring naturally on fresh and processed olives and could support mycotoxin production. The aim of this work was to investigate aflatoxin B1 (AFB1) production by fungi and its bioaccumulation in olives during storage and to study the impact of the application of Lactobacillus plantarum on the inhibition of mold development and production of AFB1. Two different treatments were applied: (i) olives with natural microflora and (ii) olives inoculated with Aspergillus flavus after elimination of natural microflora. AFB1 has been extracted from olives and quantitated by high-performance liquid chromatography using a fluorescence detector. Results showed the absence of this metabolite in the olives for the season 2008 to 2009. In 2009 to 2010, AFB1 was detected at the level of 11 μg/kg. The application of L. plantarum during the storage of olives favors the reduction of the level of AFB1 to 5.9 μg/kg correlated with a decrease in the amount of molds (86.3%). The images obtained by environmental scanning electron microscopy showed that L. plantarum was able to adhere to the olive surface and probably produce a biofilm that inhibits the multiplication of yeast and fungi by oxygen competition. Results showed an increase of antioxidant activity and amount of total phenolic compounds of olives, respectively, by 24 and 8.6%. In many olives contaminated with A. flavus, AFB1 was present at an initial level of 5.15 μg/kg and increased to 6.55 μg/kg after 8 days of storage. The biological detoxification of AFB1 in olives by L. plantarum is confirmed by the reduction of the level of AFB1 to 2.12 μg/kg on day 0 and its absence after 4 days of storage.


Two new threitol orsellinates from a sea mud-derived fungus, Ascotricha sp. ZJ-M-5.
Two new d-threitol orsellinates (1-2) were isolated from the EtOAc extract of a sea mud-derived fungus, Ascotricha sp. ZJ-M-5, cultured in Czapek Dox broth. These two compounds featured in the symmetrical substitution of orsellinic acid or acetic acid, which was established on the basis of 1D and 2D NMR experiments. The characteristic optical rotations enabled the assignment of the absolute configuration.


Sources of Health Care Among Under-5 Malawian Children With Diarrhea Episodes: An Analysis of the 2017 Demographic and Health Survey.
Diarrhea is a leading cause of morbidity and mortality in the world but mostly in Sub-Saharan Africa. These could be prevented if universal coverage of current available interventions were implemented. The study aimed to identify factors associated with the choice of health care source among caretakers seeking treatment for under-5 children with diarrhea illness. Using women's questionnaire we extracted a subset of data of children aged 0 to 59 months from the 2017 Demographic & Health Survey. Questions regarding history of childhood diarrhea for the past 24 hours or last 2 weeks prior to the survey were key in data extraction. Caregivers were asked to report the place where they sought treatment. In this study, 4 types of health facilities were defined: public, private, pharmacies, and other unspecified sources. A multinomial logistic regression model was used to identify sources of health facility used and corresponding factors associated with the choice. Factors associated with choice of health care source included education (educated women were less likely to self-medicate their children [relative risk ration (RRR) = 0.46; 95% confidence interval (CI) = 0.22-0.94]), income (better income earning families were more likely to seek care from private facility such as pharmacy [RRR = 1.87; 95% CI = 1.14-3.09]), and rural living (those in rural areas were more likely to seek treatment from other unspecified sources [RRR = 7.33, 95% CI = 1.40-38.36]). Public health facilities (79.9%) were the main source of health care service; however, reducing under-5 mortality due to diarrhea illness would require significant efforts to address other inequalities in accessing and utilizing health care services.


Dilemma in Differentiation of Spinocerebellar Ataxia Type 17 from Huntington's Disease:Comorbidity or Independent Disease?
Both Huntington's disease (HD) and Spinocerebellar ataxia 17 (SCA17) mutations showed expanded CAG repeats, with overlapping clinical manifestation: motor disorders, psychiatric symptoms and cognitive impairments. Therefore, SCA17 is also called Huntington like disease (HD-like, HDL) type 4. In this paper, we reported that one patient had 47 CAG repeats in HTT gene and 42 CAG repeats in TBP gene. There is a dilemma in differentiation of SCA 17 from HD in one patient, never been reported before. Is the diagnosis comorbidity of HD with SCA17 or HD only?


Humanization and pharmacokinetics of a monoclonal antibody with specificity for both E- and P-selectin.
E- and P-selectin (CD62E and CD62P) are cell adhesion molecules that mediate leukocyte-endothelial cell and leukocyte-platelet interactions and are involved in leukocyte recruitment during inflammation. We previously developed a murine mAb, EP-5C7 (or mEP-5C7), that binds and blocks both E- and P-selectin. When used in humans, murine mAbs have short circulating half-lives and generally induce potent human anti-mouse Ab responses. We therefore engineered a humanized, complementarity determining region-grafted version of mEP-5C7 incorporating human gamma4 heavy and kappa light chain constant regions (HuEP5C7.g4). HuEP5C7.g4 retains the specificity and avidity of mEP-5C7, binding to human E- and P-selectin but not to human L-selectin, and blocking E- and P-selectin-mediated adhesion. Surprisingly, when administered to rhesus monkeys, HuEP5C7.g4 was eliminated from the circulation very rapidly, even faster than the original murine Ab. To isolate the cause of the short serum half-life of HuEP5C7.g4, several Ab variants were constructed. A chimeric IgG4 Ab was made by replacing the humanized V regions with murine V regions. A humanized IgG2 Ab, HuEP5C7.g2, was also made by replacing the human gamma4 with a gamma2 constant region. Results from pharmacokinetic studies in rhesus monkeys demonstrated that the chimeric IgG4 is also rapidly eliminated rapidly from serum, similar to the humanized IgG4 Ab, while the humanized IgG2 Ab displays a long circulation half-life, typical of human Abs.


Laryngeal imaging by computerized tomography and magnetic resonance following radiation therapy: a need for caution.
For patients with laryngeal tumours, the use of computerized tomography (CT) or magnetic resonance imaging (MR) may facilitate accurate staging by the demonstration of cartilage invasion or tumour extension to areas such as the pre-epiglottic space. The role of imaging in the follow-up of patients after radiotherapy, however, has not been examined. A prospective study of 18 patients undergoing laryngectomy was performed. The results of pre-operative CT and MR imaging were correlated with the pathological findings from whole organ axial sections of the laryngeal specimens. In five patients (28 per cent) both CT and MR images were significantly impaired by movement artefact. In the eight patients without previous radiotherapy, seven had adequate quality imaging and both CT and MR accurately demonstrated the site, size and extent of laryngeal tumour. In eight of the ten patients following radiation therapy the presence of tumour was correctly identified, however there was a poor correlation between the imaging and pathological findings. Two patients had radionecrosis alone. Neither CT nor MR imaging could differentiate between radionecrosis and recurrent tumour.


Telepsychiatry versus face-to-face treatment: systematic review and meta-analysis of randomised controlled trials.
The COVID-19 pandemic has transformed healthcare significantly and telepsychiatry is now the primary means of treatment in some countries. To compare the efficacy of telepsychiatry and face-to-face treatment. A comprehensive meta-analysis comparing telepsychiatry with face-to-face treatment for psychiatric disorders. The primary outcome was the mean change in the standard symptom scale scores used for each psychiatric disorder. Secondary outcomes included all meta-analysable outcomes, such as all-cause discontinuation and safety/tolerability. We identified 32 studies (n = 3592 participants) across 11 mental illnesses. Disease-specific analyses showed that telepsychiatry was superior to face-to-face treatment regarding symptom improvement for depressive disorders (k = 6 studies, n = 561; standardised mean difference s.m.d. = -0.325, 95% CI -0.640 to -0.011, P = 0.043), whereas face-to-face treatment was superior to telepsychiatry for eating disorder (k = 1, n = 128; s.m.d. = 0.368, 95% CI 0.018-0.717, P = 0.039). No significant difference was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 26, n = 2290; P = 0.248). Telepsychiatry had significantly fewer all-cause discontinuations than face-to-face treatment for mild cognitive impairment (k = 1, n = 61; risk ratio RR = 0.552, 95% CI 0.312-0.975, P = 0.040), whereas the opposite was seen for substance misuse (k = 1, n = 85; RR = 37.41, 95% CI 2.356-594.1, P = 0.010). No significant difference regarding all-cause discontinuation was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 27, n = 3341; P = 0.564). Telepsychiatry achieved a symptom improvement effect for various psychiatric disorders similar to that of face-to-face treatment. However, some superiorities/inferiorities were seen across a few specific psychiatric disorders, suggesting that its efficacy may vary according to disease type.


Biology of antimicrobial resistance and approaches to combat it.
Insufficient development of new antibiotics and the rising resistance of bacteria to those that we have are putting the world at risk of losing the most widely curative class of medicines currently available. Preventing deaths from antimicrobial resistance (AMR) will require exploiting emerging knowledge not only about genetic AMR conferred by horizontal gene transfer or de novo mutations but also about phenotypic AMR, which lacks a stably heritable basis. This Review summarizes recent advances and continuing limitations in our understanding of AMR and suggests approaches for combating its clinical consequences, including identification of previously unexploited bacterial targets, new antimicrobial compounds, and improved combination drug regimens.


Analysis of oseltamivir in Tamiflu capsules using micellar electrokinetic chromatography.
A simple and rapid micellar electrokinetic chromatography (MEKC) method was developed for the analysis of an antiviral drug, oseltamivir, and its hydrolyzed product in Tamiflu capsules. Background electrolytes consisted of boric acid 10 mM, pH 10, and sodium dodecyl sulphate (SDS) 40 mM. The limit of detection (LOD) and limit of quantification (LOQ) of oseltamivir were 1.7 and 8.0 microg/ml, respectively. MEKC sweeping in a high electroosmotic flow environment for neutral analytes was also utilized to improve the sensitivity of the assay. In MEKC-sweeping mode, a buffer comprising boric acid 30 mM, pH 10, and SDS 50 mM was used. A 17-fold increase in detection sensitivity was achieved with the MEKC-sweeping method compared with the MEKC mode. Unlike in MEKC, the LOD and LOQ for oseltamivir were 0.1 and 0.3 microg/ml, respectively, using the MEKC-sweeping method. Both methods were successful in determining oseltamivir concentration in its capsule formulation, and the MEKC-sweeping method was capable of determination of the drug at lower concentrations. The hydrolyzed product of oseltamivir (oseltamivir carboxylate) was also detected using the MEKC method. Our observations revealed that the prodrug could be hydrolyzed to the active compound at alkaline pH within ca. 60 min.


Assessment of physical activity by movement registration systems in chronic pain: methodological considerations.
Physical activity assessments in chronic pain research have mostly been based on self-report. However, earlier research indicated that chronic pain patients have difficulties in estimating their own daily life activity level. Movement registration systems have been introduced to overcome the limitations of self-reported measures. However, no uniform guidelines for researchers on how to analyze and interpret movement registration data in chronic pain exist. The aim of the study was to provide recommendations for physical activity assessment based on movement registration in patients with chronic pain. First, a systematic review of the procedures and data processing techniques used in movement registration for chronic pain patients will be performed. Second, it will be discussed whether the recommendations for physical activity assessment in healthy individuals are applied in chronic pain research. Last, recommendations regarding assessment procedure and data processing for using movement registration systems in future research in patients with chronic pain will be given. In chronic pain literature, 27 articles on movement registration were identified. According to the recommendations for activity assessment in healthy individuals, the various descriptions of the assessment procedures in these articles were mostly limited. Especially, information regarding the minimal requirements for the assessment period and the method used for calculation of the final outcome variable were often lacking. It is recommended that studies in chronic pain research explicitly apply and report the criteria that have been used to define an assessment day, the total assessment time, and the method for calculating the final test outcome.


Stimulatory TSH-Receptor Antibodies and Oxidative Stress in Graves Disease.
We hypothesized that TSH-receptor (TSHR) stimulating antibodies (TSAbs) are involved in oxidative stress mechanisms in patients with Graves disease (GD). Nicotinamide adenine dinucleotide phosphate oxidase, isoform 2 (NOX2); oxidative parameters; and oxidative burst were measured in serum, urine, and whole blood from patients with GD and control subjects. Superoxide production was investigated in human embryonic kidney (HEK)-293 cells stably overexpressing the TSHR. Lipid peroxidation was determined by immunodot-blot analysis for protein-bound 4-hydroxy-2-nonenal (4-HNE) in human primary thyrocytes and HEK-293-TSHR cells. Serum NOX2 levels were markedly higher in hyperthyroid untreated vs euthyroid treated patients with GD, hyperthyroid patients with toxic nodular goiter, and euthyroid healthy control subjects (all P < 0.0001). Urine oxidative parameters were increased in patients with GD vs patients with toxic goiter (P < 0.01) and/or control subjects (P < 0.001). The maximum of the zymosan A- and phorbol 12,13-dibutyrate-induced respiratory burst of leukocytes was 1.5-fold higher in whole blood from hyperthyroid patients with GD compared with control subjects (P < 0.001 and P < 0.05). Monoclonal M22 TSAbs stimulated cAMP (HEK cells) in a dose-dependent manner. M22 (P = 0.0082), bovine TSH (P = 0.0028), and sera of hyperthyroid patients with GD (P < 0.05) increased superoxide-specific 2-hydroxyethidium levels in HEK-293 TSHR cells after 48-hour incubation vs control subjects. In contrast, triiodothyronine (T3) did not affect reactive oxygen species (ROS) production. In primary thyrocytes, the 4-HNE marker was higher in patients with GD vs control subjects at 6 and 48 hours (P = 0.02 and P = 0.04, respectively). Further, after 48-hour incubation of HEK-293 TSHR cells with patient sera, 4-HNE was higher in patients with untreated GD compared with control subjects (P < 0.05). Monoclonal M22 and polyclonal serum TSAbs augment ROS generation and/or induce lipid peroxidation.


Neurofilament Light Chain as Biomarker for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related currently incurable neurodegenerative diseases. ALS is characterized by degeneration of upper and lower motor neurons causing relentless paralysis of voluntary muscles, whereas in FTD, progressive atrophy of the frontal and temporal lobes of the brain results in deterioration of cognitive functions, language, personality, and behavior. In contrast to Alzheimer's disease (AD), ALS and FTD still lack a specific neurochemical biomarker reflecting neuropathology ex vivo. However, in the past 10 years, considerable progress has been made in the characterization of neurofilament light chain (NFL) as cerebrospinal fluid (CSF) and blood biomarker for both diseases. NFL is a structural component of the axonal cytoskeleton and is released into the CSF as a consequence of axonal damage or degeneration, thus behaving in general as a relatively non-specific marker of neuroaxonal pathology. However, in ALS, the elevation of its CSF levels exceeds that observed in most other neurological diseases, making it useful for the discrimination from mimic conditions and potentially worthy of consideration for introduction into diagnostic criteria. Moreover, NFL correlates with disease progression rate and is negatively associated with survival, thus providing prognostic information. In FTD patients, CSF NFL is elevated compared with healthy individuals and, to a lesser extent, patients with other forms of dementia, but the latter difference is not sufficient to enable a satisfying diagnostic performance at individual patient level. However, also in FTD, CSF NFL correlates with several measures of disease severity. Due to technological progress, NFL can now be quantified also in peripheral blood, where it is present at much lower concentrations compared with CSF, thus allowing less invasive sampling, scalability, and longitudinal measurements. The latter has promoted innovative studies demonstrating longitudinal kinetics of NFL in presymptomatic individuals harboring gene mutations causing ALS and FTD. Especially in ALS, NFL levels are generally stable over time, which, together with their correlation with progression rate, makes NFL an ideal pharmacodynamic biomarker for therapeutic trials. In this review, we illustrate the significance of NFL as biomarker for ALS and FTD and discuss unsolved issues and potential for future developments.


The accuracy of aspiration cytology in the diagnosis of rejection following orthotopic liver transplantation.
The role of aspiration cytology (AC) and the total corrected increment (TCI) in the diagnosis of hepatic rejection was assessed in 30 patients following 36 liver transplants. A total of 174 AC specimens were "blindly" evaluated. Patients underwent protocol AC twice weekly and when biochemical or clinical parameters suggested rejection. Hepatic rejection was only confirmed when clinical and biochemical changes were accompanied by positive histological diagnosis. In all, 103 specimens were matched against histology, the remainder assessed against retrospective clinical and biochemical diagnoses. There were 80 cytological diagnoses of rejection, confirmed in 69 specimens, and 94 diagnoses of no rejection, confirmed in 73 specimens. These figures give a sensitivity of 76.7%, a specificity of 86.9% and a positive predictive value of 86.3%. Overall, 39.7% of specimens taken more than 2 months after grafting proved to be incorrectly diagnosed. However, the accuracy was higher in 145 specimens taken within 8 weeks of transplantation, with a sensitivity of 81.3%, a specificity of 90%, a positive predictive value of 89.7% and an accuracy of 85.5%. Although histology remains the gold standard in the diagnosis of acute rejection after hepatic grafting, AC using a TCI with a positive predictive value of 86.3% may prove to be of value in monitoring liver transplant patients in the first 2 months after grafting.


Effect of storage of the du Pont lysis-centrifugation system on recovery of bacteria and fungi in a prospective clinical trial.
A commercially available lysis-centrifugation system was compared with a conventional biphasic brain heart infusion medium in a prospective clinical study of 5,125 fungal blood cultures. Recovery rates were compared between two time periods to assess the effect of 25 degrees C storage before processing by the lysis-centrifugation system. The lysis-centrifugation tubes processed within 9 h showed a significantly higher yield (3.4 versus 1.49%) for yeasts (Candida glabrata), filamentous fungi (Histoplasma capsulatum), and bacteria (8.84 versus 7.34%) (Klebsiella pneumoniae and Serratia marcescens) than did those processed after 9 h.


Sense of purpose predicts daily positive events and attenuates their influence on positive affect.
Sense of purpose has proven a consistent predictor of positive outcomes during adulthood. However, it remains unclear how purposeful adults respond to positive events in their daily lives. The current study examined whether sense of purpose predicted the frequency of daily positive events, as well as participants' affect on days with a positive event, across 8 days in an adult sample (n = 1959; mean age: 56 years). Sense of purpose predicted a greater frequency of daily positive events. Moreover, sense of purpose moderated the associations between daily positive events and daily positive affect; purposeful adults experienced less of an increase in positive affect both on the current day and the day following the positive event. Findings are discussed with respect to how purpose in life may serve homeostatic functions, insofar that having a life direction reduces responsivity to daily events and promote affect stability. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


[Endothelial morphometry and perforating keratoplasties].
50 corneal grafts were studied by specular microscopy. The endothelial cell morphology of the grafts was analysed by using a computerised image analysis system. The endothelial cell density decreased rapidly during the first three post-operative months (17%). It continued to decrease for the first year (52%, after which cell loss occurred at a slower rate (3% of the sample cell count per year). The coefficient of variation in cell area remained constant (27%). The percentage of endothelial cell loss might be closely associated with the reestablishment of the hexagonal cellular pattern. These results suggest that the endothelium of the graft is in a state of transition during the first year after surgery.


Yeast structural gene (APN1) for the major apurinic endonuclease: homology to Escherichia coli endonuclease IV.
DNA damage generated by oxygen radicals includes base-free apurinic/apyrimidinic (AP) sites and strand breaks that bear deoxyribose fragments. The yeast Saccharomyces cerevisiae repairs such DNA lesions by using a single major enzyme. We have cloned the yeast structural gene (APN1) encoding this AP endonuclease/3'-repair diesterase by immunological screening of a yeast genomic DNA expression library in lambda gt11. Gene disruption experiments confirm that the Apn1 protein accounts for greater than or equal to 97% of both AP endonuclease and DNA 3'-repair diesterase activities in yeast cell-free extracts. The DNA and predicted amino acid sequences for the APN1 gene are homologous to those for the nfo gene encoding DNA endonuclease IV of Escherichia coli. This conservation of structure between a eukaryotic enzyme and its prokaryotic counterpart underscores the fundamental nature of their roles in DNA repair.


Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate cancer tumor regression in vivo.
The identification of novel tumor-interactive chemokines and the associated insights into the molecular and cellular basis of tumor-microenvironment interactions have continued to stimulate the development of targeted cancer therapeutics. Recently, we have identified monocyte chemoattractant protein 1 (MCP-1; CCL2) as a prominent regulator of prostate cancer growth and metastasis. Using neutralizing antibodies to human CCL2 (CNTO888) and the mouse homologue CCL2/JE (C1142), we show that treatment with anti-CCL2/JE antibody (2 mg/kg, twice weekly i.p.) attenuated PC-3Luc-mediated overall tumor burden in our in vivo model of prostate cancer metastasis by 96% at 5 weeks postintracardiac injection. Anti-CCL2 inhibition was not as effective as docetaxel (40 mg/kg, every week for 3 weeks) as a single agent, but inhibition of CCL2 in combination with docetaxel significantly reduced overall tumor burden compared with docetaxel alone, and induced tumor regression relative to initial tumor burden. These data suggest an interaction between tumor-derived chemokines and host-derived chemokines acting in cooperation to promote tumor cell survival, proliferation, and metastasis.


The Effect of Education on Knowledge Regarding Breast Cancer Related Lymphedema Risk Reduction and Prevention Among Nursing Personnel.
Aim The development of lymphedema post-breast-cancer surgery has been identified as a significant burden worldwide, with nurses at the forefront of prevention and risk reduction practices. Prevention is of crucial importance to avoid lymphedema formation and its complications. This study aims to assess the knowledge gained through an educational session regarding risk reduction and prevention of breast cancer-related lymphedema (BCRL) among nursing professionals and compare the pre-test and post-test knowledge. Methods and material The research approach was quantitative in nature, and the design adopted was a pre-experimental, one-group pre-test post-test design. The study was conducted in a 400-bed multispecialty teaching hospital in Bangalore, Karnataka. After obtaining formal permission from the authorities, the participants were approached and informed about the purpose of the study. Eighty-four staff nurses working with breast cancer-related lymphedema (BCRL) patients participated in the study. The data for the study was collected using a validated questionnaire based on the National Lymphedema Network's (NLN) breast cancer-related lymphedema (BCRL) risk reduction and preventive guidelines. The questionnaire consisted of two sections. Section A consisted of the staff nurses' demographic data, and Section B consisted of questions on risk reduction and prevention of lymphedema. The pre-test was conducted, followed by a structured teaching session on risk reduction and prevention of lymphedema among 84 staff nurses working with BCRL patients. After the teaching session, the post-test was conducted. Results Descriptive and inferential statistics were used for analysis in this study. The t-test determined the statistical significance using the software SPSS (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.). The result showed that the mean knowledge score was 4.286 with SD 0.97 in the pre-test, which increased to 4.452 with SD 1.511 with a significant p-value (<0.001). Conclusion According to the study's findings, nurses must get standardized lymphedema training in order to prevent lymphedema from developing in patients having breast cancer surgery. The study's outcome has implications on the focus areas for nurses in the context of the team's adoption and dissemination of breast cancer-related lymphedema preventive measures. Key messages of this study are - 1) BCRL is an irreversible, progressive complication with no cure if not diagnosed early. 2) Poor knowledge of lymphedema prevention among nurses leads to frustration for BCRL patients. 3) Risk reduction and prevention education enable the patient to reduce BCRL complications, minimize the severity of the condition, and improve the quality of life. 4) Pre-habilitation - patient education on early diagnosis and risk reduction/prevention of BCRL reduces the cost, time, and energy for the patient and health care delivery system.


The Role of Arterial Stiffness and Central Hemodynamics in Heart Failure.
Whereas traditional understanding of left ventricular afterload was focused on a steady-state circulation model with continuous pressures and flow, a more realistic concept is emerging, taking the pulsatile nature of the heart and the arterial system into account. The most simple measure of pulsatility is brachial pulse pressure, representing the pulsatility fluctuating around the mean blood pressure level. Brachial pulse pressure is widely available, fundamentally associated with the development and treatment of heart failure (HF), but its analysis is often confounded in patients with established HF. The next step of analysis consists of arterial stiffness, central (rather than brachial) pressures, and of wave reflections. The latter are closely related to left ventricular late systolic afterload, ventricular remodeling, diastolic dysfunction, exercise capacity, and, in the long term, the risk of new-onset HF. Wave reflection may also evolve as a suitable therapeutic target for HF with preserved and reduced ejection fraction. A full understanding of ventricular-arterial coupling, however, requires dedicated analysis of time-resolved pressure and flow signals. This review provides a summary of current understanding of pulsatile hemodynamics in HF.


n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism.
Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein (CREB) transcription factor activity and p38 mitogen-activated protein kinase (MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity.


Secretion in yeast of human lysozymes with different specific activities created by replacing valine-110 with proline by site-directed mutagenesis.
Computer graphics indicate that a steric hindrance exists between valine-110 side chain of human lysozyme (EC 126.96.36.199) and an acetyl group of a modified substrate that contains N6,O-diacetylmuramic acid. To alter the substrate specificity of human lysozyme to be effective on the modified substrate, we replaced the valine-110 residue with various amino acids by site-directed mutagenesis. One of the mutant proteins (valine residue replaced with proline:P110) was secreted in Saccharomyces cerevisiae as at least four components (P110-A, P110-B, P110-C, and P110-D) with different specific activities. Two components, P110-B and P110-D, were isolated in a pure form and structurally characterized. The results suggest that this mutation lowered the lytic activity against Micrococcus lysodeikticus by changing a local conformation of the catalytic site while keeping almost the same substrate binding sites. Our results also indicate that cis/trans isomerization of prolyl peptide bonds probably occurs in vivo and that the conformational change of protein as well as point mutations in genes might influence the molecular evolution of the protein.


[Data Collection and Assessment of Costs for Prevention And Health Promotion Programs: Development of a Concept Illustrated with 'Promotion of Physical Activity'].
It is a desirable medical as well as health economic objective to achieve the best possible health effects with given financial resources. Estimating the costs of intervention programs is complex and not always possible in advance. One possibility to obtain information on costs or cost effectiveness of certain interventions is to assess programs already in existence. The aim of this article was to develop a simple, easy to understand and practical possibility of documenting costs of prevention and health promotion programs. Based on the fundamentals necessary for cost assessment, a questionnaire and a module to document the consumed resources and the resultant costs were developed. These were applied and improved within a pre-test. The developed cost module is as follows: In the left column, 5 key cost categories are listed: personnel, rooms, equipment and process, management, other costs. The cost module is a compromise between different objectives that are difficult to reconcile. On the one hand, the costs should be documented as detailed as possible and on the other, the module must be very simple to implement, as otherwise it will not be used in practice. For this purpose, it might also be useful to develop a module for each stakeholder that is aligned as closely as possible to his or her special activities. All feedback and suggestions from the pre-test were incorporated. However, some of the feedback points were project specific. Here an attempt was made to find a compromise between detail and practicality. This was done by implementing more detailed descriptions and examples in the manual. The presented module is very general. This also is a great advantage because it can be used to document the costs of completely different stakeholders. Thus, the concept presented here for cost assessment provides a first and essential component for a detailed documentation of program costs and provides the potential to check comparability and transferability of those prevention programs.


Fidelity outcomes in the National Implementing Evidence-Based Practices Project.
This article presents fidelity outcomes for five evidence-based practices that were implemented in routine public mental health settings in the National Implementing Evidence-Based Practices Project. Over a two-year period 53 community mental health centers across eight states implemented one of five evidence-based practices: supported employment, assertive community treatment, integrated dual disorders treatment, family psychoeducation, and illness management and recovery. An intervention model of practice dissemination guided the implementation. Each site used both human resources (consultant-trainers) and material resource (toolkits) to aid practice implementation and to facilitate organizational changes. External assessors rated fidelity to the evidence-based practice model every six months from baseline to two years. More than half of the sites (29 of 53, or 55%) showed high-fidelity implementation at the end of two years. Significant differences in fidelity emerged by evidence-based practice. Supported employment and assertive community treatment had higher fidelity scores at baseline and across time. Illness management and recovery and integrated dual disorders treatment had lower scores on average throughout. In general, evidence-based practices showed an increase in fidelity from baseline to 12 months, with scores leveling off between 12 and 24 months. Most mental health centers implemented these evidence-based practices with moderate to high fidelity. The critical time period for implementation was approximately 12 months, after which few gains were made, although sites sustained their attained levels of evidence-based practice fidelity for another year.


Availability of essential medicines in Pakistan-A comprehensive document analysis.
Access to essential medicines (EMs) is a basic human right. Non-availability and shortages of EMs are reported for Pakistan but there is insufficient data to define the nature and magnitude of this problem. The current study is designed to systematically analyze the medicines included in the National Essential Medicines List (NEML) for their availability through comprehensive document analysis. An expanded list of medicinal items was developed using the NEML of Pakistan (2018) to enlist individual medicines with their specifications. Registration status of the medicines was searched using three publicly accessible information sources; Pharmaguide 25th Edition, 2018-19, the on-line Drug Information System, and the Mobile Application Pharmapedia followed by a later 3-step validation of the data. The unregistered EMs were then further categorized into three subgroups in accordance with their possible remedial strategies. The 19 studied categories comprised 690 EMs and it was found that 179 (26%) of these EMs don not have a registration status. However, it was also identified that the availability of 47 (26.2%) out of 179 unregistered EMs can be enssured by strengthening compounding services, and prioritizing registration of age-appropriate formulations. Availability of another 39 (21.7%) such medicines can be ensured by revising the NEML or the product registrations for the slight differences in their different specifications. The categories showing high proportion of unregistered medicines included anti-Parkinson's medicines (100%), antidotes and other substances used in poisoning (60%), diuretics (47%), anticonvulsants/antiepileptics (42%), hormones and other endocrine medicines and contraceptives (38%), medicines for mental and behavioral disorders (30%), anti-infectives (27%), medicines for pain and palliative care (26%), medicines for neonatal care (25%), medicines for diseases of joint (25%), gastrointestinal medicines (24%) and cardiovascular medicines (15%). The study shows the absence of registration status of a significant number of EMs in Pakistan. This could be major barrier in their access. Strategies are needed to strengthen the processes of their registration on priority basis.


Recent Advances in Studying Interfacial Adsorption of Bioengineered Monoclonal Antibodies.
Monoclonal antibodies (mAbs) are an important class of biotherapeutics; as of 2020, dozens are commercialized medicines, over a hundred are in clinical trials, and many more are in preclinical developmental stages. Therapeutic mAbs are sequence modified from the wild type IgG isoforms to varying extents and can have different intrinsic structural stability. For chronic treatments in particular, high concentration (≥ 100 mg/mL) aqueous formulations are often preferred for at-home administration with a syringe-based device. MAbs, like any globular protein, are amphiphilic and readily adsorb to interfaces, potentially causing structural deformation and even unfolding. Desorption of structurally perturbed mAbs is often hypothesized to promote aggregation, potentially leading to the formation of subvisible particles and visible precipitates. Since mAbs are exposed to numerous interfaces during biomanufacturing, storage and administration, many studies have examined mAb adsorption to different interfaces under various mitigation strategies. This review examines recent published literature focusing on adsorption of bioengineered mAbs under well-defined solution and surface conditions. The focus of this review is on understanding adsorption features driven by distinct antibody domains and on recent advances in establishing model interfaces suitable for high resolution surface measurements. Our summary highlights the need to further understand the relationship between mAb interfacial adsorption and desorption, solution aggregation, and product instability during fill-finish, transport, storage and administration.


Ameloblastic carcinoma. A case report with review of literature.
Ameloblastic carcinoma is a rare odontogenic malignant tumour and has been a subject of great debate in literature. It does challenge the diagnostic acumen of pathologists, as this lesion needs to be detected at an early stage for adequate therapy. We present a case of the same with literature review.


High-resolution crystallographic map interpretation.
This article describes a method for rapid interpretation of high-resolution crystallographic electron-density maps. The implemented algorithm searches for fragments of structure found in proteins and links these together to identify uniquely the atomic structure and sequence order of the atoms within a protein. The algorithm uses a two-dimensional sub-graph isomorphism method with a subsequent post-processing step to screen the results to find correct three-dimensional solutions to each search fragment. The final screening of ambiguous solutions found is performed using incomplete difference distance matrices. The algorithm has an intrinsic error-correction technique that is necessary for analysis of experimental data and should be applicable to a number of fields of bioinfomatics.


Electron paramagnetic resonance and density-functional theory studies of Cu(II)-bis(oxamato) complexes.
In this work we present the investigation of the influence of electronic and structural variations induced by varying the N,N'-bridge on the magnetic properties of Cu(II)- bis(oxamato) complexes. For this study the complexes [Cu(opba)] (2-) ( 1, opba = o-phenylene- bis(oxamato)), [Cu(nabo)] (2-) ( 2, nabo = 2,3-naphthalene- bis(oxamato)), [Cu(acbo)] (2-) ( 3, acbo = 2,3-anthrachinone- bis(oxamato)), [Cu(pba)] (2-) ( 4, pba = propylene- bis(oxamato)), [Cu(obbo)] (2-) ( 5, obbo = o-benzyl- bis(oxamato)), and [Cu(npbo)] (2-) ( 6, npbo = 1,8-naphthalene- bis(oxamato)), and the respective structurally isomorphic Ni(II) complexes ( 8- 13) have been prepared as ( (n)Bu 4N) (+) salts. The new complex ( (n)Bu 4N) 2[Cu(R-bnbo)].2H 2O ( 7, R-bnbo = (R)-1,1'-binaphthalene-2,2'- bis(oxamato)) was synthesized and is the first chiral complex in the series of Cu(II)-bis(oxamato) complexes. The molecular structure of 7 has been determined by single crystal X-ray analysis. The Cu(II) ions of the complexes 1- 7 are eta (4)(kappa (2) N, kappa (2) O) coordinated with a more or less distorted square planar geometry for 1- 6 and a distorted tetrahedral geometry for 7. Using pulsed Electron Nuclear Double Resonance on complex 6, detailed information about the relative orientation of the hyperfine ( A) and nuclear quadrupole tensors ( Q) of the coordinating nitrogens with respect to the g tensor were obtained. Electron Paramagnetic Resonance studies in the X, Q, and W-band at variable temperatures were carried out to extract g and A values of N ligands and Cu ion for 1- 7. The hyperfine values were interpreted in terms of spin population on the corresponding atoms. The obtained trends of the spin population for the monomeric building blocks were shown to correlate to the trends obtained in the dependence of the exchange interaction of the corresponding trinuclear complexes on their geometry.


Environmental Health: A Position Paper From the American College of Physicians.
Environmental health refers to the health effects associated with environmental factors, such as air pollution, water contamination, and climate change. Environmental hazards are associated with poor outcomes in common diseases, including diabetes and heart disease. In this position paper, the American College of Physicians (ACP) seeks to inform physicians about environmental health and offers policymakers recommendations to reduce the adverse health consequences of climate change, improve air and water quality, reduce exposure to toxic substances, and address environmental injustice. ACP affirms that all communities, including people of color, people with low income, and marginalized populations, deserve to live in a healthy environment.


Surgical treatment for necrotizing enterocolitis: a new score to extreme surveillance.
The time to perform a surgical intervention in necrotizing enterocolitis remains a challenge for the pediatric surgeon. We design a novel score system to predict infants in high risk for the development of surgical necrotizing enterocolitis. A total of 124 consecutively patients diagnosed of NEC at the University Hospital of A Coruña, Spain were included in the study. Associations were analyzed by bivariate and multivariate analysis. We applied multivariate logistic regression modeling to identify factors that could provide accurate risk of surgical NEC. We include not only analytical and radiological parameters or physical examination, but we also analyzed prenatal, sociodemographic, perinatal and peripartum variables that conditioned the presence of predispose factors, which could determine the debut of this entity and in its progression. Patients requiring surgical treatment have presented an antecedent of respiratory distress (worsening of the ventilatory requirements) in the perinatal period, they present higher values of glycemia at diagnosis of the illness, debut with coagulopathy and have in laboratory findings marked neutrophilia. Our score system obtained by combining several parameters could detect infants at risk of developing severe necrotizing enterocolitis improving the morbidity and mortality associated with delay in the surgical treatment.


Wet weights of dental plaques.
A method for weighing samples of plaque using a weighing assembly comprising a sample-bearing boat, held in a closed capsule to avoid moisture loss to room or balance environment is described. The system described is an objective device for measuring, by wet weight the amounts of plaque accumulating under various conditions of oral hygiene.


Initial experience with a telerobotic system to remotely navigate and automatically reposition standard steerable EP catheters.
The use of robotic systems in cardiac interventional procedures is growing. The insertion and maneuvering in the human body of electrophysiology (EP) catheters is currently carried out manually under fluoroscopic guidance, resulting in operator fatigue and prolonged x-ray exposure. We report our initial animal experience with a novel telerobotic system (TS) to remotely navigate and automatically reposition standard steerable EP catheters within the heart. We developed a TS able to guide, as a "robotic hand," EP catheters without the need of dedicated catheters and cumbersome devices. During tests on three sheep, catheter navigation and repositioning to 12 predefined endocardial targets were previously performed by conventional manual procedure and then using the TS implemented with an automatic catheter repositioning function. All the predefined targets were reached under fluoroscopy visualization, and procedural times were measured during catheter navigation and repositioning. The use of the TS slightly reduced the time necessary for catheter navigation compared with the conventional manual procedure (13.0 +/- 5.6 vs 16.1 +/- 6.4 seconds, p < 0.001) and significantly decreased the time for a precise catheter repositioning (9.2 +/- 2.5 vs 17.8 +/- 7.1 sec, p < 0.001). The TS proved to be a promising tool for remote navigation of standard EP catheters reducing the time necessary for catheter repositioning.


Renal pathophysiologic role of cortical tubular inclusion bodies.
Renal tubular inclusion bodies are rarely associated with drug administration. The authors describe the finding of renal cortical tubular intranuclear and intracytoplasmic inclusion bodies associated with the oral administration of a norepinephrine/serotonin reuptake inhibitor (NSRI) test article in Sprague-Dawley (SD) rats. Rats were given an NSRI daily for 4 weeks, and kidney histopathologic, ultrastructural pathology, and immunohistochemical examinations were performed. Round eosinophilic intranuclear inclusion bodies were observed histologically in the tubular epithelial cells of the renal cortex in male and female SD rats given the NSRI compound. No evidence of degeneration or necrosis was noted in the inclusion-containing renal cells. By ultrastructural pathology, inclusion bodies consisted of finely granular, amorphous, and uniformly stained nonmembrane-bound material. By immunohistochemistry, inclusion bodies stained positive for d-amino acid oxidase (DAO) protein. In addition, similar inclusion bodies were noted in the cytoplasmic tubular epithelial compartment by ultrastructural and immunohistochemical examination. This is the first description of these renal inclusion bodies after an NSRI test article administration in SD rats. Such drug-induced renal inclusion bodies are rat-specific, do not represent an expression of nephrotoxicity, represent altered metabolism of d-amino acids, and are not relevant to human safety risk assessment.


Magnitude of Multidrug Resistance among Bacterial Isolates from Surgical Site Infections in Two National Referral Hospitals in Asmara, Eritrea.
The World Health Organization has emphasized the importance of understanding the epidemiology of MDR organisms from a local standpoint. Here, we report on a spectrum of bacteria associated with surgical site infections in two referral hospitals in Eritrea and the associated antibiotic susceptibility patterns. This survey was conducted between February and June 2017. A total of 83 patients receiving treatment for various surgical conditions were included. Swabs from infected surgical sites were collected using Levine technique and processed using standard microbiological procedures. In vitro antimicrobial susceptibility testing was performed on Mueller-Hinton Agar by the Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. The data were analyzed using SPSS version 20. A total of 116 isolates were recovered from 83 patients. In total, 67 (58%) and 49 (42%) of the isolates were Gram-positive and Gram-negative bacteria, respectively. The most common isolates included Citrobacter spp., Klebsiella spp., Escherichia coli, Proteus spp., Pseudomonas aeruginosa, Salmonella spp., Enterobacter spp., and Acinetobacter spp. In contrast, Staphylococcus aureus, CONS, and Streptococcus viridians were the predominant Gram-positive isolates. All the Staphylococcus aureus isolates were resistant to penicillin. MRSA phenotype was observed in 70% of the isolates. Vancomycin, clindamycin, and erythromycin resistance were observed in 60%, 25%, and 25% of the isolates, respectively. Furthermore, a high proportion (91%) of the Gram-negative bacteria were resistant to ampicillin and 100% of the Pseudomonas aeruginosa and Escherichia coli isolates were resistant to >5 of the tested antibiotics. The two Acinetobacter isolates were resistant to >7 antimicrobial agents. We also noted that 4 (60%) of the Klebsiella isolates were resistant to >5 antimicrobial agents. Possible pan-drug-resistant (PDR) strains were also isolated. Due to the high frequency of MDR isolates reported in this study, the development and implementation of suitable infection control policies and guidelines is imperative.


Primary care physician characteristics associated with cancer screening: a retrospective cohort study in Ontario, Canada.
Primary care physicians can serve as both facilitators and barriers to cancer screening, particularly for under-screened groups such as immigrant patients. The objective of this study was to inform physician-targeted interventions by identifying primary care physician characteristics associated with cancer screening for their eligible patients, for their eligible immigrant patients, and for foreign-trained physicians, for their eligible immigrant patients from the same world region. A population-based retrospective cohort study was performed, looking back 3 years from 31 December 2010. The study was performed in urban primary care practices in Ontario, Canada's largest province. A total of 6303 physicians serving 1,156,627 women eligible for breast cancer screening, 2,730,380 women eligible for cervical screening, and 2,260,569 patients eligible for colorectal screening participated. Appropriate breast screening was defined as at least one mammogram in the previous 2 years, appropriate cervical screening was defined as at least one Pap test in the previous 3 years, and appropriate colorectal screening as at least one fecal occult blood test in the previous 2 years or at least one colonoscopy or barium enema in the previous 10 years. Just fewer than 40% of physicians were female, and 26.1% were foreign trained. In multivariable analyses, physicians who attended medical schools in the Caribbean/Latin America, the Middle East/North Africa, South Asia, and Western Europe were less likely to screen their patients than Canadian graduates. South Asian-trained physicians were significantly less likely to screen South Asian women for cervical cancer than other foreign-trained physicians who were seeing region-congruent patients (adjusted odds ratio: 0.56 [95% confidence interval 0.32-0.98] versus physicians from the USA, Australia and New Zealand). South Asian patients were the most vulnerable to under-screening, and decreasing patient income quintile was consistently associated with lower likelihood of screening, although less so for immigrant patients. This study highlights certain physician characteristics that are associated with cancer screening for eligible patients, including immigrant patients, and that should be considered when designing physician-targeted interventions. We have also highlighted an ethnic community, South Asians, which requires particular attention, both among its patients and its primary care providers. Future research should further explore the reasons for these findings.


[Study on chiral selective inclusion and retention characteristics of cis-trans isomers and enantiomers of sertraline with HP-beta-CD as a mobile phase modifier].
The effect of the inclusion complex formation of cis-trans isomers and enantiomers of sertraline with added hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in the reversed-phase high performance liquid chromatographic (RP-HPLC) mobile phase on the retention and selectivity has been investigated. Graphs of 1/k vs [HP-beta-CD] in different experimental conditions gave good linear relationships, indicating the stoichiometry ratio of 1:1. The binding constants between HP-beta-CD and cis-trans isomers and enantiomers of sertraline were calculated by using the liquid chromatographic retention values. Meanwhile, the influences of pH value, buffer ionic strength, concentration of organic modifier and temperature on the binding constant have been studied in detail. Quantitative equations were obtained for the correlations between the binding constants and the above influencing parameters. On the other hand, the thermodynamic parameters of the inclusion complexes were determined for the four inclusion complexes. The study characterized the chiral recognition selectivity between sertraline isomers and HP-beta-CD. It was demonstrated that the chiral selectivity values were in the same sequence as delta(j,i) deltaH and delta(j,i) deltaS and opposite order against the binding constants of inclusion complexes. Both enthalpic and entropic terms were negative for cis-trans isomers and enantiomers of sertraline. It was confirmed that enthalpy-driven separations occurred in consistency with the results. The influence of temperature on retention behavior showed that the process of inclusion was exothermic, in consistency with the calculated thermodynamic parameters.


Breast cancer cell survival signal is affected by bergapten combined with an ultraviolet irradiation.
In this study we have reported that bergapten (B) and bergapten plus UV (PUVA) are able to significantly affect MCF-7, ZR-75 and SKBR-3 breast cancer cell proliferations. B induced a lowering of PI3K/AKT survival signal in MCF-7 cells even in presence of IGF-I stimulation. Furthermore, B and in a higher extent, PUVA up-regulated the p53 mRNA and the protein content. An increased co-association between p21 WAF and proliferating cell nuclear antigen (PCNA) has been observed in PUVA-treated MCF-7 cells, thus inhibiting DNA replication. These results highlight how B, and its photoactivated compound, exert antiproliferative effects and induce apoptotic responses in breast cancer cells.


Helical chromonema coiling is conserved in eukaryotes.
Efficient chromatin condensation is required to transport chromosomes during mitosis and meiosis, forming daughter cells. While it is well accepted that these processes follow fundamental rules, there has been a controversial debate for more than 140 years on whether the higher-order chromatin organization in chromosomes is evolutionarily conserved. Here, we summarize historical and recent investigations based on classical and modern methods. In particular, classical light microscopy observations based on living, fixed, and treated chromosomes covering a wide range of plant and animal species, and even in single-cell eukaryotes suggest that the chromatids of large chromosomes are formed by a coiled chromatin thread, named the chromonema. More recently, these findings were confirmed by electron and super-resolution microscopy, oligo-FISH, molecular interaction data, and polymer simulation. Altogether, we describe common and divergent features of coiled chromonemata in different species. We hypothesize that chromonema coiling in large chromosomes is a fundamental feature established early during the evolution of eukaryotes to handle increasing genome sizes.


Identification of 5' capped structure and 3' terminal sequence of hepatitis E virus isolated from Morocco.
To examine 5' and 3' terminal sequences of hepatitis E virus (HEV) isolated from Morocco, to confirm 5' methylated cap structure of the genome, and to investigate whether the 3' UTR can be used to distinguish HEV genotypes instead of HEV complete genome sequence. RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) was employed to obtain the 5' and 3' terminal sequences of HEV Morocco strain. The 3' UTR sequence of the Morocco strain was compared with that of the other 29 HEV strains using the DNAStar software. The 5' PCR product was obtained only from the RLM-RACE based on the capped RNA template. The 5' UTR of the Morocco strain had 26 nucleotides, and the 3' UTR had 65 nucleotides upstream to the polyA. The 5' UTR between HEV strains had only point mutations of nucleotides. The phylogenetic tree based on the sequences of 3' UTR was not the same as that based on the complete sequences. The genome of HEV Morocco strain was methylated cap structure. The 3' terminal sequence can not be used for distinguishing HEV genotype for all HEV strains in place of the whole HEV genome sequence.


Characteristics of scrub typhus, murine typhus, and Q fever among elderly patients: Prolonged prothrombin time as a predictor for severity.
The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18-64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002-2011. Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01-0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33-9.99). The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications.


Activity of maturation promoting factor (MPF) and mitogen-activated protein kinase (MAPK) after parthenogenetic activation of ovine oocytes.
The maturation promoting factor (MPF) and mitogen-activated protein kinase (MAPK) are the key regulators of both meiotic and mitotic cell cycles. Knowledge of the dynamics of these two kinases during the transition from meiosis to mitosis would be of great importance for cloning by nuclear transfer. In this study, experiments were designed to assay the changes of MPF and MAP kinase activity of in vitro matured ovine oocytes after chemical activation and culture in 0 mM or 2 mM 6-dimethylaminopurine (6-DMAP) for 12 h. Moreover, to determine the biological significance of the fluctuations of MPF, activated oocytes were fused with GV-staged partners. The biochemical results showed that the high MPF activity of MII oocytes fell to basal level precipitously within the first hour after activation, started to increase at 6-8 h, rising to 80 +/- 4% of MII after 12 h. MAPK activity decreased to a low level 4 h after activation, increased between 6-12 h, but remained below 30 +/- 3.6% of MII values. The incubation with 6-DMAP had no effect on the kinetics of MPF and MAP kinase activity. Fusion of MII oocytes to GV partners induced rapid breakdown of the GV, whereas no breakdown occurred when GV were fused with eggs in the first hours post activation. Interestingly, the high biochemical levels of MPF activity at 8-12 h after activation were not able to induce GVBD in fusion partners.


Relevance of chronic lyme disease to family medicine as a complex multidimensional chronic disease construct: a systematic review.
Lyme disease has become a global public health problem and a prototype of an emerging infection. Both treatment-refractory infection and symptoms that are related to Borrelia burgdorferi infection remain subject to controversy. Because of the absence of solid evidence on prevalence, causes, diagnostic criteria, tools and treatment options, the role of autoimmunity to residual or persisting antigens, and the role of a toxin or other bacterial-associated products that are responsible for the symptoms and signs, chronic Lyme disease (CLD) remains a relatively poorly understood chronic disease construct. The role and performance of family medicine in the detection, integrative treatment, and follow-up of CLD are not well studied either. The purpose of this paper is to describe insights into the complexity of CLD as a multidimensional chronic disease construct and its relevance to family medicine by means of a systematic literature review.


Psychotropic drug-induced weight gain alleviated with orlistat: a case series.
Weight gain is a common side effect associated with antidepressant, anxiolytic, and antipsychotic drug use. Obesity is a risk factor for several other disorders, including hypertension, diabetes, and coronary artery disease. To date, there have been few safe, well-tolerated, and effective pharmacological agents available to alleviate weight gain in general, and virtually no studies specific to psychiatric drug-induced weight gain. This case series looks at the use of orlistat, a reversible inhibitor of lipases approved by the US Food and Drug Administration for obesity management, naturalistically in 13 patients with weight gain secondary to psychotropic drug use. The results showed that orlistat, administered in 3 daily doses with meals, was safe, well-tolerated, and effective, resulting in an average weight loss of 35% during an acute treatment period of about 3 months.


Thymic hormonal activity on human peripheral blood lymphocytes in vitro. II. Enhancement of the production of immune interferon by activated cells.
The thymic extract TP-1 significantly enhanced the production of immune interferon (IF) by human peripheral blood mononuclear cells in Con A- or Raji- but not PHA-induced cultures. TP-1 effect was more pronounced under conditions of low IF production. The effect was evident before cell proliferation took place and without necessary concurrent effect of TP-1 on the blastogenic response. TP-1 had no detectable effect on nonactivated cultures. The enhancement of IF production by TP-1 to the degree demonstrated here necessitates consideration of its possible effects in every assay of thymic hormones that involves lectin or allogeneic stimulation of lymphocytes.


IFN-gamma regulation of the type IV class II transactivator promoter in astrocytes.
The transcriptional activation of class II MHC genes requires the class II transactivator (CIITA) protein, a regulator that is essential for both constitutive and IFN-gamma-inducible class II MHC expression. The CIITA gene is controlled by multiple independent promoters; two promoters direct constitutive expression, while another, the type IV CIITA promoter, mediates IFN-gamma-induced expression. We investigated the molecular regulation of IFN-gamma-induced type IV CIITA promoter activity in astrocytes. IFN-gamma inducibility of the type IV CIITA promoter is dependent on three cis-acting elements contained within a 154-bp fragment of the promoter; the proximal IFN-gamma activation sequence (GAS) element, the E box, and the proximal IFN regulatory factor (IRF) element. Two IFN-gamma-activated transcription factors, STAT-1alpha and IRF-1, bind the proximal GAS and IRF elements, respectively. The E box binds upstream stimulating factor-1 (USF-1), a constitutively expressed transcription factor. Furthermore, STAT-1alpha binding to the proximal GAS element is dependent on the binding of USF-1 to the adjacent E box. Functionally, the proximal IRF element is essential for IFN-gamma induction of type IV CIITA promoter activity, while the proximal GAS and E box elements contribute to the IFN-gamma inducibility of this promoter. In astrocytes, TNF-alpha enhances IFN-gamma-induced class II MHC transcription. Our results demonstrate that TNF-alpha does not enhance IFN-gamma-induced transcriptional activation of the type IV CIITA promoter, indicating that the enhancing effect of TNF-alpha is mediated downstream of CIITA transcription. These results define the molecular basis of IFN-gamma activation of the type IV CIITA promoter in astrocytes.


Among the three striatin family members, SG2NA was first to arise during evolution.
Striatin, SG2NA, and zinedin constitute a three-member subfamily of WD-40 repeat proteins. They are found only in metazoans and are likely to have scaffolding functions. Apart from WD-40 repeats, they also have a caveolin-binding motif, a coiled-coil structure, and a calmodulin-binding domain. This paper focuses on the analysis of their evolution as a paradigm of understanding the metazoan scaffolds. Each member of the family forms distinct phylogenetic clusters, wherein striatins, SG2NAs, and zinedins have 13, 10, and 9 conserved motifs, respectively. Furthermore, two of those motifs each in striatin and in zinedin and three in SG2NA are exclusive for the respective subfamily. Of those exclusive motifs for SG2NA, two encompass the caveolin-binding and coiled-coiled domains. Collectively, they show the presence of 11 conserved motifs, suggestive of convergence of individual motifs and creation of patterns. A prokaryotic WD-40 repeat motif pCM-I was found only in the corresponding domain of SG2NA but not in other family members. It is thus hypothesized that striatin family members have evolved from bacteria, and SG2NA was the first member to arise.


Significant association between simple renal cysts and arterial blood pressure.
To test the hypothesis that there is an association between simple renal cysts and arterial blood pressure (BP). The study comprised a review of the case-notes of 115 patients (mean age 67.7 years, range 31-91) in whom renal cyst(s) was an incidental ultrasonographic finding, and 115 age- and sex-matched control patients. The notes were reviewed without knowledge of the origin or treatment. The systolic and diastolic BP were significantly higher in patients with a cyst(s) than in control patients (P = 0.031 and P = 0.0034; mean difference 6.9 mmHg and 5.0 mmHg, respectively). In those aged 30-70 years, the presence of one or more simple renal cysts increased the risk of having a diastolic BP > or = 95 mmHg from seven in 58 to 17 in 58 patients (P = 0.038). The association between simple renal cysts and higher arterial BP probably arises from underlying renal disease causing both. Occasionally it is possible that renal ischaemia caused by cyst expansion, and therefore increased renin release, generates the elevation in BP. If so, methods to identify such cysts should be developed.


Mode of action of a minor xylanase from Thermoascus aurantiacus on polysaccharides and model substrates.
The mode of action of a minor xylanase on a variety of polysaccharides and model substrates was investigated. The enzyme was excreted by Thermoascus aurantiacus grown in solid state fermentation (SSF). The purified enzyme had a molecular mass of 33,000. Thin layer chromatography analysis showed that the endoxylanase liberated short fragments from polysaccharides. The enzyme hydrolysed aryl-beta-D-cellobioside and the chromogenic (fluorogenic) 4-methylumbelliferyl-beta-glycosides of xylobiose (MeUmbXyl2) and xylotriose (MeUmbXyl3) at the agluconic linkage. The results suggested that the endoxylanase belonged to family 10.


Insights into the architecture of the Ure2p yeast protein assemblies from helical twisted fibrils.
The protein Ure2 from baker's yeast is associated with a heritable and transmissible phenotypic change in the yeast Saccharomyces cerevisiae. Such prion properties are thought to arise from the fact that Ure2p is able to self-assemble into insoluble fibrils. Assemblies of Ure2p are composed of full-length proteins in which the structure of the globular, functional, C-terminal domain is retained. We have carried out structural studies on full-length, wild-type Ure2p fibrils with a regularly twisted morphology. Using electron microscopy and cryo-electron microscopy with image analysis we show high-resolution images of the twisted filaments revealing details within the fibrillar structure. We examine these details in light of recent proposed models and discuss how this new information contributes to an understanding of the architecture of Ure2p yeast prion fibrils.


Efficacy and safety of 'true' cinnamon (Cinnamomum zeylanicum) as a pharmaceutical agent in diabetes: a systematic review and meta-analysis.
Diabetes is a leading cause of morbidity and mortality worldwide. Studies have frequently looked at dietary components beneficial in treatment and prevention. We aim to systematically evaluate the literature on the safety and efficacy of Cinnamomum zeylanicum on diabetes. A comprehensive search of the literature was conducted in the following databases; PubMed, Web of Science, Biological Abstracts, SciVerse Scopus, SciVerse ScienceDierect, CINAHL and The Cochrane Library. A meta-analysis of studies examining the effect of C. zeylanicum extracts on clinical and biochemical parameters was conducted. Data were analysed using RevMan v5.1.2. The literature search identified 16 studies on C. zeylanicum (five in-vitro, six in-vivo and five in-vivo/in-vitro). However, there were no human studies. In-vitro C. zeylanicum demonstrated a potential for reducing post-prandial intestinal glucose absorption by inhibiting pancreatic α-amylase and α-glucosidase, stimulating cellular glucose uptake by membrane translocation of glucose transporter-4, stimulating glucose metabolism and glycogen synthesis, inhibiting gluconeogenesis and stimulating insulin release and potentiating insulin receptor activity. The beneficial effects of C. zeylanicum in animals include attenuation of diabetes associated weight loss, reduction of fasting blood glucose, LDL and HbA(1c) , increasing HDL cholesterol and increasing circulating insulin levels. Cinnamomum zeylanicum also significantly improved metabolic derangements associated with insulin resistance. It also showed beneficial effects against diabetic neuropathy and nephropathy, with no significant toxic effects on liver and kidney and a significantly high therapeutic window. Cinnamomum zeylanicum demonstrates numerous beneficial effects both in vitro and in vivo as a potential therapeutic agent for diabetes. However, further randomized clinical trials are required to establish therapeutic safety and efficacy.


Modified Whipple-Child pancreaticoduodenectomy with anastomosis on jejunal loop in continuity. Presentation of surgical technique and preliminary observations on 45 patients.
Cephalic pancreaticoduodenectomy (CPD) is the only current treatment method that can provide long-term survival in patients with periampullary tumors. This study is a prospective study conducted between 2010 and 2016 in Hepato-Biliary-Pancreatic Center of "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania, where 57 modified Whipple-Child CPDs with anastomoses on jejunal loop in continuity were performed, in patients with periampullary tumors. Twelve patients, who had undergone prior biliodigestive derivations or biliary drainage using endoscopic retrograde cholangio-pancreatography (ERCP), with stenting of the common bile duct, were excluded from the study. In 45 patients with modified Whipple-Child CPDs with anastomosis on jejunal loop in continuity, which were included in the study, overall morbidity rate was 22.22%. Postoperative mortality (within 30 days after the surgery) was 6.66% and six months and one year survival rates, excluding the four patients who died postoperatively, were 91.11% and 80%, respectively, with a median survival of 32 months. The mean operative time was 300 minutes, ranging between 240 and 390 minutes. Modified Whipple-Child CPD with anastomoses on jejunal loop in continuity seems to be a therapeutic method promising a decreased overall morbidity rate and a good quality of life and offering a distant survival rate, which is consistent, so far, with data reported in the literature.


Innervation of the striated muscle of the membranous urethra of the male dog.
To identify the functional innervation of the striated muscle layer of the post-prostatic urethra of male dogs. Detailed anatomic dissection of the pelvic and pudendal nerves was carried out. The pressure and contractile responses to stimulation of these nerves were recorded in vivo and in vitro. Small branches of the pelvic nerve entered the membranous urethra but passed through the striated muscle to the inner smooth muscle layer. Stimulation of the nerve with 1 msec pulses at 10 Hz produced a slow contraction of the urethra which was unaffected by d-tubocurarine. Pudendal nerve branches entered the striated layer from the caudal end. Stimulation produced a rapid, visible contraction that was abolished by d-tubocurarine. Field stimulation of isolated strips of striated muscle resulted only in rapid, d-tubocurarine sensitive contractions. The striated muscle of the membranous urethra is innervated exclusively by the pudendal nerve.


Inspiratory muscle training does not improve clinical outcomes in 3-week COPD rehabilitation: results from a randomised controlled trial.
The value of inspiratory muscle training (IMT) in pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) is unclear. The RIMTCORE (Routine Inspiratory Muscle Training within COPD Rehabilitation) randomised controlled trial examined the effectiveness of IMT added to pulmonary rehabilitation.In total, 611 COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) received a 3-week inpatient pulmonary rehabilitation, of which 602 patients were included in the intention-to-treat analyses. The intervention group (n=300) received highly intensive IMT and the control group (n=302) received sham IMT. The primary outcome was maximal inspiratory pressure (PImax). The secondary outcomes were 6-min walk distance, dyspnoea, quality of life and lung function. Outcomes were assessed pre- and post-pulmonary rehabilitation. ANCOVA was used.The intervention group showed higher effects in PImax (p<0.001) and forced inspiratory volume in 1 s (p=0.013). All other outcomes in both study groups improved significantly, but without further between-group differences. Sex and pulmonary rehabilitation admission shortly after hospitalisation modified quality of life effects.IMT as an add-on to a 3-week pulmonary rehabilitation improves inspiratory muscle strength, but does not provide additional benefits in terms of exercise capacity, quality of life or dyspnoea. A general recommendation for COPD patients to add IMT to a 3-week pulmonary rehabilitation cannot be made.


Atypical appearance of hepatic hemangiomas with contrast-enhanced ultrasound.
To describe the atypical enhancement pattern of hepatic hemangiomas on contrast-enhanced sonography. 22 patients with hepatic hemangiomas that were atypical on contrast-enhanced ultrasound were included in the study, all of them were confirmd by biopsy or surgery pathology. Atypical appearance of hepatic hemangiomas on contrast-enhanced ultrasound were divided into seven subtypes: (i) peripheral nodular enhancement in the arterial phase with centripedal filling, hypoechoic change in the delayed phase; (ii) peripheral circular enhancement; (iii) peripheral nodular enhancement; (iv) none enhancement; (v) septal enhancement; (vi) a central enhancing focus in the arterial phase, followed by a centrifugal enhancement in the portal venous phase, hypoechoic change in the delayed phase; (vii) slowly spoke wheel enhancement. Atypical appearance of hepatic hemangiomas were various. Radiologists should be aware. Establishing knowledge of the entire spectrum of atypical hepatic hemangiomas may benefit the rational approach to future cases.


Anti-N-methyl-D-aspartate receptor antibody encephalitis: An important cause of encephalitis in young adults. A report of two cases.
Encephalitis is a clinical syndrome which can include altered mental status, motor and sensory deficits, altered behavior including personality changes, speech and movement disorders and seizures. While the overall incidence of encephalitis is not known, it is common enough that most pediatric and adolescent medicine physicians will have seen at least one case. Peak times of risk include the newborn period and middle-to-late adolescence. 1 It is important for clinicians to have a working knowledge of the broad range of encephalitis etiologies: viral, post-viral, toxic, auto-immune, and paraneoplastic. We discuss two cases of encephalitis in young adult women with ovarian teratoma and production of anti-N-methyl-D-aspartate receptor (NMDAR) antibodies.