Cerebellar and cerebral white matter changes in Parkinson's disease with resting tremor.
Cerebellum modulates the amplitude of resting tremor in Parkinson's disease (PD) via cerebello-thalamo-cortical (CTC) circuit. Tremor-related white matter alterations have been identified in PD patients by pathological studies, but in vivo evidence is limited; the influence of such cerebellar white matter alterations on tremor-related brain network, including CTC circuit, is also unclear. In this study, we investigated the cerebral and cerebellar white matter alterations in PD patients with resting tremor using diffusion tensor imaging (DTI). In this study, 30 PD patients with resting tremor (PDWR), 26 PD patients without resting tremor (PDNR), and 30 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort were included. Tract-based spatial statistics (TBSS) and region of interest-based analyses were conducted to determine white matter difference. Correlation analysis between DTI measures and clinical characteristics was also performed. In the whole brain, TBSS and region of interest-based analyses identified higher fractional anisotropy (FA) value, lower mean diffusivity (MD) value, and lower radial diffusivity (RD) in multiple fibers. In the cerebellum, TBSS analysis revealed significantly higher FA value, decreased RD value as well as MD value in multiple cerebellar tracts including the inferior cerebellar peduncle (ICP) and middle cerebellar peduncle (MCP) when comparing the PDWR with HC, and higher FA value in the MCP when compared with PDNR. We identified better white matter integrity in the cerebrum and cerebellum in PDWR indicating a potential association between the cerebral and cerebellar white matter and resting tremor in PD.


Stability and loading properties of curcumin encapsulated in Chlorella vulgaris.
Curcumin (Cur), a polyphenols with pharmacological function, was successfully encapsulated in algae (Alg) cell (Chlorella vulgaris) as confirmed by fluorescence microscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and Fourier transform-infrared spectroscopy (FT-IR). Fluorescence micrographs, TGA, DSC and FTIR spectra suggested the hypothesis inclusion Cur in Nano-empty spaces inside cell wall of Alg. The TGA analysis showed that the thermal stability of Alg and Cur at algae/curcumin complex was 3.8% and 33% higher than their free forms at 0-300°C and 300-600°C ranges, respectively. After encapsulation in Alg cells, the photostability of Cur was enhanced by about 2.5-fold. Adsorption isotherm of Cur into Alg was fitted with the Freundlich isotherm. The microcapsules were loaded with Cur up to about 55% w/w which is much higher than other reported bio-carriers. In conclusion, the data proved that Chlorella vulgaris cell can be used as a new stable carrier for Cur.


Helicopter transportation of burn patients.
Analysis of 437 consecutive acute burn patients transported to our burn center revealed 339 transported by ground and 98 by helicopter. There were 18 air transport patients from within a 25-mile-radius, and 80 flown further than 25 miles. Mean age was the same in all groups (P>0.05). Percent total body surface area (TBSA) burned was 8.26% in ground transport patients, significantly less than the 20.35% (within 25 miles) and 21.40% (greater than 25 miles) seen in helicopter transports (P<0.0001). Three percent of ground transport patients and 28% of helicopter patients had inhalation injury (P<0.0001). There was no difference in incidence of inhalation injury among helicopter groups (28 vs. 29%, P=0.8). In patients with coexistent inhalation injury, the mean TBSA burned was significantly larger when compared with the TBSA of burns without inhalation injury (P<0.001). Air transported groups contained patients whose status was not critical based upon lack of inhalation injury and small burn size, and who could have been transported by ground. Non clinical factors such as insurance status, desire to keep ground ambulances in their community, and competing helicopter services reluctant to refuse to transport a patient appears to be factors in choosing air ambulance transportation. Regional single helicopter services and regional cooperative ground ambulance services should reduce use of helicopter transport of burn patients when it is not clinically indicated.


Teaching Tacting of Private Events Based on Public Accompaniments: Effects of Contingencies, Audience Control, and Stimulus Complexity.
Our current understanding of the role of private events in the science of behavior is based largely on Skinner's natural science interpretation of private events. Skinner described public accompaniments as one source of control for a verbal community to differentially reinforce verbal behavior regarding private events. In this study, we developed an experimental analogue to study variables influencing tacting of private events. The participant had exclusive access to one set of stimuli (the private stimuli), and the experimenter attempted to teach tacts for private stimuli based on their correspondence with public stimuli accessible to both the experimenter and participant. Results of experiments 1 and 2 demonstrated that reports of private stimuli were a function of degree of public-private correspondence, reinforcement contingency, and audience control. In some cases, we encountered reports controlled exclusively by public stimuli. Results of experiment 3 showed that public control was less likely when public stimuli were more complex and the experimenter had a unique behavioral history with respect to those stimuli that was not shared by the learner. The orderly patterns of data obtained suggest that analogue arrangements might be a useful, and even necessary, starting point for experimental investigations of how private events may enter into the analysis of behavior.


Perioperative strategies and technical modifications to the Nuss repair for pectus excavatum in pediatric patients: a large volume, single institution experience.
The safety and efficacy of minimally invasive pectus excavatum repair have been demonstrated over the last twenty years. However, technical details and perioperative management strategies continue to be debated. The aim of the present study is to review a large single-institution experience with the modified Nuss procedure. A retrospective review was performed of patients who underwent primary pectus excavatum repair at a single tertiary hospital via a modified Nuss procedure that included: no thoracoscopy, retrosternal dissection achieved via a left-to-right thoracic approach, four-point stabilization of the bar, and no routine epidural analgesia. Data collected included demographics, preoperative symptoms, operative characteristics, hospital charges and postoperative outcomes. A total of 336 pediatric patients were identified. No cardiac perforations occurred and the rate of pericarditis was 0.6%. Contemporary rates of bar displacement have fallen to 1.2%. Routine use of chlorhexidine scrub reduced superficial site infections to 0.7%. Two patients (0.6%) with severe recurrence required reoperation. Bars were removed after an average period of 31.7(SD 13.2) months, with satisfactory cosmetic and functional results in 94.9% of cases. We report here a single-institution large volume experience, including modifications to the Nuss procedure that make the technique simpler and safer, improve results, and minimize hospital charges.


A systematic review and meta-analysis of 90 cohort studies of social isolation, loneliness and mortality.
The associations between social isolation, loneliness and the risk of mortality from all causes, cardiovascular disease (CVD) and cancer are controversial. We systematically reviewed prospective studies on the association between social isolation, loneliness and mortality outcomes in adults aged 18 years or older, as well as studies on these relationships in individuals with CVD or cancer, and conducted a meta-analysis. The study protocol was registered with PROSPERO (reg. no. CRD42022299959). A total of 90 prospective cohort studies including 2,205,199 individuals were included. Here we show that, in the general population, both social isolation and loneliness were significantly associated with an increased risk of all-cause mortality (pooled effect size for social isolation, 1.32; 95% confidence interval (CI), 1.26 to 1.39; P < 0.001; pooled effect size for loneliness, 1.14; 95% CI, 1.08 to 1.20; P < 0.001) and cancer mortality (pooled effect size for social isolation, 1.24; 95% CI, 1.19 to 1.28; P < 0.001; pooled effect size for loneliness, 1.09; 95% CI, 1.01 to 1.17; P = 0.030). Social isolation also increased the risk of CVD mortality (1.34; 95% CI, 1.25 to 1.44; P < 0.001). There was an increased risk of all-cause mortality in socially isolated individuals with CVD (1.28; 95% CI, 1.10 to 1.48; P = 0.001) or breast cancer (1.51; 95% CI, 1.34 to 1.70; P < 0.001), and individuals with breast cancer had a higher cancer-specific mortality owing to social isolation (1.33; 95% CI, 1.02 to 1.75; P = 0.038). Greater focus on social isolation and loneliness may help improve people's well-being and mortality risk.


Moving towards high-resolution descriptions of the molecular interactions and structural rearrangements of the human hepatitis B core protein.
The human hepatitis B virus core protein (HBc) forms icosahedral capsids and plays central roles in viral replication. The critical interactions that HBc makes prior to capsid formation (potential drug targets) have proved refractory to structural characterisation as HBc aggressively forms capsids. Our current structural understanding of HBc interactions is therefore capsid-centric, and this view has been limited by the resolution of cryo-electron microscopy and the inherent difficulties in getting high-quality crystals of viral capsids. To augment these approaches, we used capsid-dissociating conditions, solution NMR, and biophysical methodologies to directly characterise, at atomic resolution, the structural properties of dimeric HBc, as well as its dynamics and intermolecular interactions. Dimeric HBc recapitulates the structural properties and binding interactions of HBc within the context of capsids. Antiviral peptides induced long-range structural asymmetry in dimeric HBc, providing new insights into how ligand binding can effect communication between different regions of HBc and, therefore, between the capsid interior and the capsid exterior. Our work also paves the way for detailed descriptions of the previously invisible early stages of replication involving soluble HBc.


Time-trend of hospitalizations for anogenital warts in Veneto region in the HPV vaccination era: a cross sectional study (2007-2018).
Human papillomavirus (HPV) is a common sexually transmitted pathogen and the cause of several cancers and of anogenital warts. With this study, we estimated the trend of hospitalizations for anogenital warts (AGWs) in the Veneto region (Italy) from 2007 to 2018. The analysis included all the hospital discharge records of public and accredited private hospitals occurred in Veneto residents in the timespan 2007-2018. The ICD9-CM code 078.11 considered were those associated with condyloma acuminatum and those associated with surgical interventions for vulval/vaginal warts, penile warts anal warts. Annual total and sex- and age-specific hospitalization rates and trends were calculated and correlated with the different HPV vaccine coverage over the study period. We observed an overall reduction of hospitalization rates for AGWs: from 15.0 hospitalizations every 100,000 Veneto residents in years 2007-08 to 10.9 hospitalizations every 100,000 Veneto residents in year 2017-18 (- 37.4%; p < 0.05). Reduction has been caused by a drop in hospitalizations in females - from a rate of 20.4/100,000 in 2007-2008 to a rate of 10.8/100,000 in 2017-18 (AAPC: -7.1; 95%CI: - 10.6;-3.4); while in males, we observed a slight - but not statistically significant - increase in hospitalization rates. The marked decline in hospitalization rates for AGWs in Veneto Region is probably attributable to the high coverage rates of HPV vaccination programs implemented since 2008.


Decreased serum albumin level indicates poor prognosis of COVID-19 patients: hepatic injury analysis from 2,623 hospitalized cases.
Coronavirus disease 2019 (COVID-19) is a global pandemic which has caused numerous deaths worldwide. The present study investigated the roles of hypoproteinemia in the clinical outcome and liver dysfunction of COVID-19 patients. In this retrospective study, we extracted data from 2,623 clinically confirmed adult COVID-19 patients (>18 years old) between January 29, 2020 and March 6, 2020 in Tongji Hospital, Wuhan, China. The patients were divided into three groups-non-critically ill, critically ill, and death groups-in accordance with the Chinese Clinical Guideline for COVID-19. Serum albumin, low-density lipoproteins cholesterol (LDL-C), and high-density lipoproteins cholesterol (HDL-C) concentrations and inflammatory cytokines levels were measured and compared among these three groups. The median age of these 2,623 patients was 64 years old (interquartile range (IQR), 52-71). Among the patients enrolled in the study, 2,008 (76.6%) were diagnosed as non-critically ill and 615 (23.4%) were critically ill patients, including 383 (14.6%) critically ill survivors and 232 (8.8%) critically ill deaths in the hospital. Marked hypoalbuminemia occurred in 38.2%, 71.2%, and 82.4% patients in non-critically ill, critically ill, and death groups, respectively, on admission and 45.9%, 77.7%, and 95.6% of these three groups, respectively, during hospitalization. We also discovered that serum low-density lipoprotein (LDL) and HDL levels were significantly lower in critically ill and death groups compared to non-critically ill group. Meanwhile, the patients displayed dramatically elevated levels of serum inflammatory factors, while a markedly prolonged activated partial thromboplastin time (APTT) in critically ill patients reflected coagulopathy. This study suggests that COVID-19-induced cytokine storm causes hepatotoxicity and subsequently critical hypoalbuminemia, which are associated with exacerbation of disease-associated inflammatory responses and progression of the disease and ultimately leads to death for some critically ill patients.


Macrophage-dependent stimulation of T cell-depleted spleen cells by Clostridium difficile toxin A and calcium ionophore.
Clostridium difficile toxin A causes severe intestinal inflammation and fluid secretion in rabbit ileum and is chemotactic for neutrophils in vitro. The mechanism of intestinal injury produced by toxin A appears to involve direct epithelial cell damage as well as recruitment of an inflammatory cell response. The current study was undertaken to determine if toxin A can directly stimulate a proliferative response in lymphocytes. Highly purified toxin A, in the presence of the calcium ionophore, ionomycin, stimulated substantial [3H]thymidine incorporation by murine splenic lymphocytes, which was maximal at 10(-9) M toxin A and 800 ng/ml ionomycin. Removal of T cells with anti-Thy-1.2 antibody plus complement had no effect on the proliferative response induced by toxin A. However, [3H]thymidine incorporation in response to toxin A was significantly inhibited (P less than 0.001) by the removal of macrophages from splenocyte suspensions and was restored by the addition of peritoneal macrophages or cell-free supernatant from toxin A-treated macrophage cultures. Analysis of the toxin A-treated macrophage supernatants showed high levels of IL-1, but not IL-2 or IL-4. The combination of recombinant IL-1 plus ionomycin was found to stimulate [3H]thymidine incorporation by T cell-depleted splenic lymphocytes. These results suggest that toxin A stimulates the release of IL-1, and possibly other factors, from macrophages which can costimulate murine B lymphocytes.


Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial.
There is a high unmet need for treatment regimens that increase the chance of long-term remission and possibly cure for women with newly diagnosed advanced ovarian cancer. In the primary analysis of SOLO1/GOG 3004, the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib significantly improved progression-free survival versus placebo in patients with a BRCA mutation; median progression-free survival was not reached. Here, we report an updated, post-hoc analysis of progression-free survival from SOLO1, after 5 years of follow-up. SOLO1 was a randomised, double-blind, placebo-controlled, phase 3 trial, done across 118 centres in 15 countries, that enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1 and with BRCA-mutated, newly diagnosed, advanced, high-grade serous or endometrioid ovarian cancer with a complete or partial clinical response after platinum-based chemotherapy. Patients were randomly assigned (2:1) via a web-based or interactive voice-response system to receive olaparib (300 mg twice daily) or placebo tablets orally as maintenance monotherapy for up to 2 years; randomisation was by blocks and was stratified according to clinical response after platinum-based chemotherapy. Patients, treatment providers, and data assessors were masked to group assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy is reported in the intention-to-treat population and safety in patients who received at least one dose of treatment. The data cutoff for this updated, post-hoc analysis was March 5, 2020. This trial is registered with ClinicalTrials.gov (NCT01844986) and is ongoing but closed to new participants. Between Sept 3, 2013, and March 6, 2015, 260 patients were randomly assigned to olaparib and 131 to placebo. The median treatment duration was 24·6 months (IQR 11·2-24·9) in the olaparib group and 13·9 months (8·0-24·8) in the placebo group; median follow-up was 4·8 years (2·8-5·3) in the olaparib group and 5·0 years (2·6-5·3) in the placebo group. In this post-hoc analysis, median progression-free survival was 56·0 months (95% CI 41·9-not reached) with olaparib versus 13·8 months (11·1-18·2) with placebo (hazard ratio 0·33 [95% CI 0·25-0·43]). The most common grade 3-4 adverse events were anaemia (57 [22%] of 260 patients receiving olaparib vs two [2%] of 130 receiving placebo) and neutropenia (22 [8%] vs six [5%]), and serious adverse events occurred in 55 (21%) of 260 patients in the olaparib group and 17 (13%) of 130 in the placebo group. No treatment-related adverse events that occurred during study treatment or up to 30 days after discontinuation were reported as leading to death. No additional cases of myelodysplastic syndrome or acute myeloid leukaemia were reported since the primary data cutoff, including after the 30-day safety follow-up period. For patients with newly diagnosed advanced ovarian cancer and a BRCA mutation, after, to our knowledge, the longest follow-up for any randomised controlled trial of a PARP inhibitor in this setting, the benefit derived from 2 years' maintenance therapy with olaparib was sustained beyond the end of treatment, extending median progression-free survival past 4·5 years. These results support the use of maintenance olaparib as a standard of care in this setting. AstraZeneca; Merck Sharpe & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA.


Controlling morphology of peptide-based soft structures by covalent modifications.
Control of gross morphology of soft matter remains an area of continued interest. Towards this goal, this paper describes conjugation of mannose residues and introduction of thiol functionalities to diphenylalanine (FF) dipeptide, a fibrillating motif from amyloid-β peptide, as covalent modifiers of its solution-phase self-assembly process. It was found that covalent attachment of a single mannose residue to FF leads to the retention of tubular structures, whereas the conjugation of two mannose units, linked through a Lys residue, resulted in a dramatic change from tubular morphology to spherical structures. However, a similar switch to spherical objects could be achieved by introducing a thiol residue in the mono-mannosylated FF dipeptide. Interestingly, these glycopeptides also exhibited interaction with concanavalin A, thereby providing an indirect evidence for the availability of mannose units for the process of lectin-carbohydrate interaction in the self-organized state.


Synthetic insulin-like growth factor II.
Human insulin-like growth factor II with 67 amino acid residues and three disulfide bridges has been synthesized by the solid-phase method. Homogeneity of the synthetic product is ascertained by chromatofocusing, high performance liquid chromatography and amino acid analysis. In both radioimmunoassay and radioreceptor assay, the synthetic product is indistinguishable from the natural hormone.


Deciphering the pharmacological mechanism of the Chinese formula huanglian-jie-du decoction in the treatment of ischemic stroke using a systems biology-based strategy.
Huanglian-jie-du decoction (HLJDD) is an important multiherb remedy in TCM, which is recently demonstrated to be effective to treat ischemic stroke. Here, we aimed to investigate the pharmacological mechanisms of HLJDD in the treatment of ischemic stroke using systems biology approaches. Putative targets of HLJDD were predicted using MetaDrug. An interaction network of putative HLJDD targets and known therapeutic targets for the treatment of ischemic stroke was then constructed, and candidate HLJDD targets were identified by calculating topological features, including 'Degree', 'Node-betweenness', 'Closeness', and 'K-coreness'. The binding efficiencies of the candidate HLJDD targets with the corresponding compositive compounds were further validated by a molecular docking simulation. A total of 809 putative targets were obtained for 168 compositive compounds in HLJDD. Additionally, 39 putative targets were common to all four herbs of HLJDD. Next, 49 major nodes were identified as candidate HLJDD targets due to their network topological importance. The enrichment analysis based on the Gene Ontology (GO) annotation system and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that candidate HLJDD targets were more frequently involved in G-protein-coupled receptor signaling pathways, neuroactive ligand-receptor interactions and gap junctions, which all played important roles in the progression of ischemic stroke. Finally, the molecular docking simulation showed that 170 pairs of chemical components and candidate HLJDD targets had strong binding efficiencies. This study has developed for the first time a comprehensive systems approach integrating drug target prediction, network analysis and molecular docking simulation to reveal the relationships between the herbs contained in HLJDD and their putative targets and ischemic stroke-related pathways.


Isolation and determination of quaternary ammonium compounds by means of amberlite XAD-columns and thin layer chromatography.
The potentials of XAD-columns for the isolation of quaternary ammonium compounds from aqueous media have been investigated. When adequate amounts of counter ions (perchlorate, chloride, phosphate, nitrate) were added to the aqueous sample, to the column pretreatment fluid and to the aqueous washing fluid, most quaternary compounds investigated were retained on the column and could be recovered by elution with methanol. This approach proved also suitable for urine. Quantitation of quaternaries isolated in this way from urine samples could be performed on silicagel thin layer plates through visualization with iodine, followed by densitometric evaluation. For decamethonium detection limits were 0.1 micrograms/ml. Recoveries at the 1 micrograms/ml level were between 80--90% with variation coefficients of less than 10%.


Erythropoietic protoporphyria: a study of its psychosocial aspects.
Twelve people with erythropoietic protoporphyria (EPP) answered a written questionnaire and were subsequently interviewed. They had all learned to cope with the disease, but found their lives severely restricted. They found that they were seldom understood by others and they suffered considerable physical and psychological distress. Only one subject had any knowledge of the pathophysiological mechanism of EPP. The physician has an important role in recognizing this condition and in providing practical advice and supportive counselling to help patients cope with the disease.


Galectin-3 expression in follicular tumours: an immunohistochemical study of its use as a marker of follicular carcinoma.
Galectin-3, a member of the beta-galactoside binding family of lectins, has been regarded as a useful tool for discriminating malignant tumours from benign nodules of the thyroid, including the distinction between follicular carcinoma and adenoma. However, there are follicular tumours with unclear vascular or capsular invasion, which makes diagnosis more difficult. In this study, we investigated the relationship between galectin-3 expression and the degree of vascular or capsular invasion of follicular tumours. We immunohistochemically investigated galectin-3 expression in 260 cases of follicular tumour with various degrees of vascular or capsular invasion classified into four categories. The galectin-3 expression level significantly increased with the degree of vascular or capsular invasion (p<0.0001). However, its diagnostic value for follicular carcinoma was not high because the sensitivity and specificity were 68.7% and 57.5%, respectively. Our findings suggest that galectin-3 plays a role in the transformation of follicular tumours from benign to malignant; however, when diagnosing follicular tumours, the presence of this protein should not be required for diagnosing malignant transformation in all cases. Therefore, we must conclude that galectin-3 should only be considered an adjuvant marker for follicular carcinoma.


Stellate ganglion influence on static compliance and surface layer lipids in cat lungs.
In order to determine the effects of stellate ganglion stimulation (SGS) on static lung compliance, pressure-volume relationships were measured on lungs in situ in cats anesthetized with ketamine. The lungs were inflated with 100% oxygen to 100, 93.75, 87.5, 81.25, 75, 50, and 25% TLC as determined at 20 cm H2O transpulmonary pressure. After a maximal filling, lungs were inflated twice to each volume, alternating unstimulated and SGS conditions. Static lung compliance was decreased by SGS at 93.75 (5.7 +/- 0.4 (SE) vs. 5.4 +/- 0.4 ml/cm H2O; P less than 0.05) and 87.5% TLC (6)6 +/- 0.6 vs 6.0 +/- 0.5 ml/cm H2O; P less than 0.05). In order to assess possible effects of SGS on surfactant that might be related to the loss of compliance, lung lipids and proteins obtained during SGS were quantitated. Total phospholipid (TPL) increased from 3.22 +/- 0.33 to 4.16 +/- 0.23 mg/g lung after 1 min 7V SGS (P less than 0.05) and to 4.58 +/- 0.61 mg/g lung after 4 min 20V (P less than 0.05). The ratio of cholesterol (chol) to disaturated phosphatidylcholine (DSPC) decreased after 4 and 6 min, and may have resulted in increased surface tension forces at high lung volumes. The data from this study lend support to previous findings which showed that the compliance decrease during SGS may be related to increased surface tension forces.


Original Design of the Limberg Flap: An Opposite Triangular Flap.
The aim of this study was to identify the original design of the Limberg flap.Publications by the original author, Limberg, and his original designs of the so-called "Limberg flap" were searched in PubMed. These included his original monograph written in Russian (Mathematical Principles of Local Plastic Procedures on the Surface of the Human Body, 1946), the first English paper ("Design of Local Flaps," 1966), and English translation of his book by Wolfe (1984).Three figures that may be the prototypes of the Limberg flap were found in the 1946 Russian monograph. One figure involved designing unilaterally active opposite triangular flaps, placed on a lateral incision on the edge of the defect. Another was closure of a defect of the nasal dorsum with a cheek flap with opposite triangular flaps with lateral incision angles of 30° and 105°. The third depicted closure of the lateral section of a fusiform defect using adjacent opposite triangular patches. In 1966 English chapter, he described the rotation of a triangular flap for the closure of a rhomboid defect. Two standing cones and a lying cone are still formed and should be sited where the tissues are lax enough to compensate. In 1984 English translation, the "unilaterally active opposite triangular flaps" and "rotation of a triangular flap in the closure of a rhomboid defect," were translated as "convergent triangular flaps" and "convergent triangular flaps" respectively.Limberg first called original design of the flap "opposite triangular flap," and later "local triangular flap" for closing rhomboid skin defects.


Oral motor treatment: Effects of therapeutic feeding on articulatory skills.
The prevalence of feeding problems is over 20% in typically developing children and over 70% in children with developmental disabilities. Oral motor therapy targeting feeding disorders may have secondary/indirect positive effects on co-morbid articulation disorders in young children. The purpose of this study was to examine such indirect effects. Seven young children with feeding problems were assessed via a known standardized articulation test upon admission for feeding therapy. They received a 4-week oral motor treatment protocol toward the development of age-appropriate feeding and swallowing, consisting of the application of tongue pressure and therapeutic spoon placement. At the conclusion of the oral motor feeding therapy, the participants' articulatory skills were tested again. Results indicated a significant difference in the pre- and post-treatment scores on the articulation test as well as on parents' reports on their child's speech intelligibility.


Epigenetic Signatures and Plasticity of Intestinal and Other Stem Cells.
The cardinal properties of adult tissue stem cells are self-renewal and the ability to generate diverse resident cell types. The daily losses of terminally differentiated intestinal, skin, and blood cells require "professional" stem cells to produce replacements. This occurs by continuous expansion of stem cells and their immediate progeny, followed by coordinated activation of divergent transcriptional programs to generate stable cells with diverse functions. Other tissues turn over slowly, if at all, and vary widely in strategies for facultative stem cell activity or interconversion among mature resident cell types (transdifferentiation). Cell fate potential is programmed in tissue-specific configurations of chromatin, which restrict the complement of available genes and cis-regulatory elements, hence allowing specific cell types to arise. Using as a model the transcriptional and chromatin basis of cell differentiation and dedifferentiation in intestinal crypts, we discuss here how self-renewing and other tissues execute homeostatic and injury-responsive stem cell activity.


Hyaluronic acid grafted PLGA copolymer nanoparticles enhance the targeted delivery of Bromelain in Ehrlich's Ascites Carcinoma.
Rapidly increasing malignant neoplastic disease demands immediate attention. Several dietary compounds have recently emerged as strong anti-cancerous agents. Among, Bromelain (BL), a protease from pineapple plant, was used to enhance its anti-cancerous efficacy using nanotechnology. In lieu of this, hyaluronic acid (HA) grafted PLGA copolymer, having tumor targeting ability, was developed. BL was encapsulated in copolymer to obtain BL-copolymer nanoparticles (NPs) that ranged between 140 to 281nm in size. NPs exhibited higher cellular uptake and cytotoxicity in cells with high CD44 expression as compared with non-targeted NPs. In vivo results on tumor bearing mice showed that NPs were efficient in suppressing the tumor growth. Hence, the formulation could be used as a self-targeting drug delivery cargo for the remission of cancer.


Interferon gamma encapsulated into liposomes enhances the activity of monocytes and natural killer cells and has antiproliferative effects on tumor cells in vitro.
The effects of human interferon gamma (IFN gamma) encapsulated into liposomes were investigated in vitro. Monocytes were induced to release a cytotoxic factor with either IFN gamma encapsulated into liposomes, free IFN gamma or lipopolysaccharide (LPS). If IFN gamma was applied in the liposomal form, less IFN activity was required to stimulate monocytes. Most of the cytotoxic factor was secreted during the first 4 h of stimulation. The cytotoxic factor in supernatants from PMNLs was completely neutralized by a monospecific polyclonal antiserum to tumor necrosis factor (TNF). Combining subthreshold doses of IFN gamma liposomes or IFN gamma with lipopolysaccharide synergistically enhanced the release of TNF. In fluorescence analysis, altered expression of the class II HLA-DR antigen on LeuM3 positive monocytes was induced with IFN gamma liposomes as well as with IFN gamma. Not only monocytes but also natural killer (NK) cells were stimulated to higher cytotoxicity by IFN gamma liposomes in a dose-dependent manner. In comparison with IFN gamma, the same amount of activity was necessary for adequate stimulation of NK-cells against the K562 target cells. Furthermore, the antiproliferative effects of IFN gamma liposomes and free IFN gamma on several human tumor cell lines was compared. Among several cell lines tested, U937 and A549 turned out to be sensitive to IFN gamma, and both cell lines reacted with 50% growth inhibition at a lower amount of gamma presented by liposomes than in the free form. These data show production of IFN gamma liposomes which possess immunomodulatory and antiproliferative activity in vitro. In several of the test systems studied, liposome-encapsulated IFN gamma was more effective than free IFN gamma.


Catecholaminergic systems and amygdala kindling development. Effects of bilateral lesions of substantia nigra dopaminergic or locus coeruleus noradrenergic neurones.
The effects of the bilateral and selective destruction of substantia nigra (SN) dopaminergic or locus coeruleus (LC) noradrenergic neurones, consecutive to a local injection of 6-hydroxydopamine, were studied on the development of amygdala kindling. Immunohistochemical controls of lesions were performed using selective dopamine (DA) or norepinephrine (NE) antibodies. The results demonstrated that a massive destruction of SN pars compacta neurones did not modify the rate of kindling development. Conversely, the lesions of LC neurones (sparing lateral tegmental nuclei) markedly facilitated the development of amygdala kindling. This effect was related to the extent of NE denervation. Together, these results suggest that DA is not strongly involved in the development of kindling, and that the nigrostriatal output does not play a major role in the generalization of kindled seizures. In contrast, they confirm an inhibitory influence exerted by LC noradrenergic ascending pathways on the development of kindling.


Lipids in the developing enamel of the rat incisor. Parallel histochemical and biochemical investigations.
Morphologic examination of the developing enamel of rat incisors showed the presence of cell processes and remnants. Histochemical investigation of rapid-frozen freeze-substituted samples, using p-phenylenediamine or a phosphotungstic acid chromic acid mixture, revealed osmiophilic components which were extractable in chloroform-methanol solution and were located inside the tubule-like structures of the extracellular matrix. The presecretory cell-rich and developing enamel zones underwent quantitative and qualitative lipid analysis. Comparison of the biochemical data as well as of the morphological observations, suggests a cellular origin for enamel lipids randomly adsorbed by extracellular matrix components during enamel processing. The nature of the material which appeared as an osmiophilic intra-tubular filling is still unresolved.


Familial frontal fibrosing alopecia treated with dutasteride, minoxidil and artificial hair transplantation.
A 46-year-old premenopausal woman presented with familial frontal fibrosis alopecia affecting the temples bilaterally. The diagnosis was confirmed histologically. Her past history included rheumatoid arthritis treated with hydroxychloroquine 400 mg daily and methotrexate 20 mg weekly. Serial intralesional injections of triamcinolone did not limit the progression of hair loss. Treatment with dutasteride 0.1 mg daily and minoxidil 1 mg daily stabilised hair loss and artificial fibre hair transplantation initially led to a satisfactory cosmetic outcome. Unfortunately, the patient developed implant folliculitis uncontrolled by antibiotics, necessitating the removal of the fibres 12 months post-transplantation.


Systemic therapy for pancreatic cancer.
Pancreatic adenocarcinoma is typically diagnosed at an advanced stage, at which point systemic therapy becomes the primary modality of treatment. Although gemcitabine monotherapy has remained the standard of care for the past decade, a number of large studies conducted over the past several years have suggested that some advantages may be derived from the use of combination therapy, such as the addition of a platinum agent to gemcitabine. The application of pharmacokinetic principles to drug delivery may confer additional benefit as well. Furthermore, with an increasing understanding of the cellular and stromal events that govern pancreatic tumor maintenance, molecularly targeted agents are under active investigation and may prove to serve a critical role in our therapeutic armamentarium. The combination of standard cytotoxic agents and these newer targeted compounds offers promise that we will be able to make significant inroads in improving clinical outcomes for patients with advanced pancreatic cancer.


Synthesis of a molecular mimic of the Glc1Man9 oligoside as potential inhibitor of calnexin binding to DeltaF508 CFTR protein.
Deletion of phenylalanine at position 508 of the CFTR protein is associated with a severe form of cystic fibrosis. Biosynthetic arrest of the misfolded DeltaF508 CFTR protein in the endoplasmic reticulum is due to prolonged interaction with protein chaperones. In order to overcome this retention and thereby restore the delivery of the protein to the plasma membrane, a molecular mimic of the glycoprotein oligoside moiety has been designed and synthesized. Ability of this mimic to inhibit the binding of the natural Glc1Man9GlcNAc oligoside to calnexin has been measured.


Patient' and social aspects related to complementary mistletoe therapy in patients with breast cancer: A systematic review commissioned by the German agency for Health Technology Assessment.
To mitigate side effects of conventional cancer care and improve quality of life, many patients with breast cancer in German-speaking countries opt for mistletoe therapy in addition to standard treatment. To understand the value for users, we evaluated the domain "Patient and Social aspects" in a health technology assessment on complementary mistletoe therapy in patients with breast cancer. A systematic review was conducted according to PRISMA guidelines. Fifteen electronic databases and the internet were searched. Qualitative studies were analyzed using qualitative content analysis; quantitative studies were systematically summarized in evidence tables. Seventeen studies out of 1203 screened publications with 4765 patients and 869 healthcare professionals were included in the review. The median proportion of patients using mistletoe therapy was 26.7% (range: 7.3-46.3%). Predictors for use were younger age and higher educational level. Main reasons for patients' use of mistletoe therapy were to leave nothing untried and to be actively involved in the treatment process. Reasons against use were related to a lack of knowledge or uncertainty regarding effectiveness and safety. Physicians mainly aimed to support the patient's physical condition as main reason for use and a lack of resources and knowledge as main reason against use. Mistletoe therapy was commonly used in the treatment of breast cancer despite a lack of scientific knowledge among patients and physicians. Transparent communication on motivation for use and its potential effect enables realistic expectations. Relatively small samples of mistletoe therapy users limit the representativeness and validity of our results.


Measurement of the (14)N nuclear quadrupole resonance frequencies by the solid effect.
(1)H-(14)N nuclear quadrupole double resonance using magnetic field cycling between high and low magnetic field and solid effect in the low magnetic field is analyzed in details. The transition probabilities per unit time for the solid-effect transitions are calculated. The double resonance spectra are calculated in the limiting cases of fast and slow nitrogen spin-lattice relaxation. The double resonance spectra are measured in histamine and quinolinic acid. The experimental spectra are analyzed and the (14)N NQR frequencies are determined.


Effects of cytochalasin B on low-density lipoproteins metabolism by cultured human fibroblasts.
The role of cytoplasmic microfilaments in the metabolism of low-density lipoprotein by human fibroblasts was studied with the aid of cytochalasin B. At concentrations of 5--40 nmol/ml cytochalasin increased the surface binding but decreased the endocytosis of 125I-labelled low-density lipoprotein. Subsequent studies indicated that these changes reflected a reduction of the rate of internalisation of low-density lipoprotein receptors. Independent inhibitory effects were also observed on low-density lipoprotein degradation and on the cellular release of the trichloroacetic acid-soluble degradation products.


Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus: A randomized, crossover trial.
We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range. This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR; <70 mg/dL). The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index >5 was significantly reduced (8.6 % vs 23.7 %, P < 0.001). The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM.


Application of spectrofluorometry to the prediction of PHB concentrations in a fed-batch process.
On-line estimation of biopolymer production during fermentation would be a useful adjunct to the development of strategies for process control and optimization. This study examined the applicability of spectrofluorometry, along with other on-line measurements, for the prediction of poly-beta-hydroxybutyric acid (PHB) concentrations in a high-cell density fed-batch fermentation of Ralstonia eutropha. Models previously used for modelling PHB evolution with time are not sufficiently accurate for situations where transient intermediate accumulations or PHB degradation occur. Thus, the mass balance in the model was modified to account for these situations. An estimation algorithm was developed that is based on a hybrid model consisting of a dynamic mass balance of PHB where the main reaction coefficient was regressed with respect to spectrofluorometric data. The regression between the kinetic parameter and the spectrofluorometric data was accomplished using partial least squares (PLS) regression to avoid high sensitivity to noise expected from highly correlated data, such as the spectrofluorometric readings. The model accounts for dynamics of intermediates and in this way allows the prediction of dynamic behaviour in PHB concentrations that cannot be predicted with other reported mathematical models.


Hemolymph Levels of Methyl Farnesoate During Ovarian Development of the Swimming Crab Portunus trituberculatus, and Its Relation to Transcript Levels of HMG-CoA Reductase and Farnesoic Acid O-Methyltransferase.
Methyl farnesoate (MF) is a sesquiterpene compound and the crustacean homolog of insect juvenile hormones. MF has multiple physiological functions involving the regulation of molting, reproduction, metamorphogenesis, behavior, and osmoregulation. In this study, the hemolymph levels of MF during ovarian development of Portunus trituberculatus were measured by gas chromatography-mass spectrometry (GC-MS). The results showed that the hemolymph level of MF in P. trituberculatus was low during stages I and II, increased considerably in stage III, and remained high in stage IV. Correlation of MF level with ovarian maturation indicates the putative stimulatory role of MF in this physiological process. As 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) and farnesoic acid O-methyltransferase (FAMeT) are two essential enzymes in MF biosynthesis, their transcript levels during ovarian development were detected by quantitative real-time PCR (qPCR). Transcript levels of HMGR and FAMeT exhibited variation trends similar to that of the level of MF in hemolymph. This might indicate that high expression of HMGR and FAMeT could result in an increase in the production of MF, which ultimately affects ovarian development.


Improved basal medium for Y-1 mouse adrenal cortex tumor cells in culture. I. Dependence of growth and steroid response on calcium ion concentration.
An improved basal medium is presented that required only minimal supplementation with dialyzed fetal bovine serum or bovine serum albumin and fetuin to be comparable to Ham's F-10, which requires 15% horse serum (HS) and 2.5% fetal bovine serum (FBS) for the growth and function of Y-1, mouse adrenal cortex tumor, cells. Cell monolayers maintained for up to 2 weeks without any protein supplementation have retained their steroid response to ACTH. The medium differs from Ham's F-10 in its buffer composition and higher calcium-ion concentration. This medium should be a useful adjunct to studies pertaining to steroid and lipid intermediary metabolism, the retention of a specialized physiological function in a chemically defined medium, and the mechanism of hormonal response.


Rapid diagnosis of different goose astrovirus genotypes with Taqman-based duplex real-time quantitative PCR.
The epidemic of goose astrovirus (GoAstV) caused huge losses to the poultry industry. Epidemiological studies in China revealed 2 circulating genotypes of GoAstV, but there is a lack of differential diagnosis tools. By analyzing all published genomes of GoAstV, this study designed specific PCR primers and Taqman probes to recognize different genotypes of GoAstV. After optimization and verification, this study developed a Taqman-based real-time quantitative PCR method that is capable of differential diagnosis. The established qPCR exhibited detection limitations of 100 copies/μL or 10 copies/μL, respectively, for GoAstV genotype 1 and genotype 2, and showed no false positive for other common avian viruses. This method was then used to analyze 72 samples collected from different regions in Jiangxi, and the results were verified by genome sequencing and phylogenetic analysis. These results revealed a complex coinfection of GoAstV different genotypes in China, highlighting the importance of long-term focus on the prevalence and genome evolution of GoAstV.


Teaching Cellular Architecture: The Global Status of Histology Education.
Histology or microanatomy is the science of the structure and function of tissues and organs in metazoic organisms at the cellular level. By definition, histology is dependent on a variety of microscope techniques, usually light or more recently virtual, as well as electron microscopy. Since its inception more than two centuries ago, histology has been an integral component of biomedical education, specifically for medical, dental, and veterinary students. Traditionally, histology has been taught in two sequential phases, first a didactic transfer of information to learners and secondly a laboratory segment in which students develop the skill of analyzing micrographic images. In this chapter, the authors provide an overview of how histology is currently taught in different global regions. This overview also outlines which educational strategies and technologies are used, and how the local and cultural environment influences the histology education of medical and other students in different countries and continents. Also discussed are current trends that change the teaching of this basic science subject.


Acoustic noise reduction for spiral MRI by gradient derating.
To show that the acoustic noise of spiral MRI can be reduced by derating the gradients with minimal penalty to image quality and scan time, and to illustrate an algorithm for optimal choice of derating parameters. Acoustic noise level was measured and compared for various values of maximum gradient amplitude and slew rate for T1 -weighted spin-echo spiral scans while maintaining image contrast, FOV and resolution, and readout time. A full gradient trajectory and a derated gradient (undersampled) trajectory were chosen for a volunteer scan followed by parallel imaging-aided reconstruction to illustrate comparable image SNR. Two auto-derating methods, which prioritize slew rate and gradient amplitude, respectively, were derived using analytical results from the WHIRLED PEAS variant of spiral waveforms and compared in their acoustic noise level under test use cases. Derating the gradients made the scan quieter by 16.6 dB(A) on average than a full gradient trajectory and required an undersampling factor R = 2 in order to maintain scan time, with no appreciable penalty in image SNR. Prioritizing reduced slew rate resulted in maximal loudness reduction. Scanner gradients can often be derated to reduce the acoustic noise for spiral MRI with minimal penalty in scan time and image quality with the help of parallel imaging. An automatic slew-priority derating method that maximizes loudness reduction is given.


Aggressive angiomyxoma presenting with back and perineal bulge; a complex surgical approach: A case report.
Aggressive angiomyxoma is a rare mesenchymal tumor occurring predominantly in the pelvi-perineal region. It is more common in females during their reproductive age. Our focus is on the surgical approach for a recurrent angiomyxoma. We present a case of a 36-year-old female patient with a recurrent lower back and perineal bulges. One year ago, she had the same presentation and underwent resection of that mass in a peripheral hospital without available information. Five months later, she started to have the same bulge. Computed tomography scan and true cut biopsy were suggestive of angiomyxoma with single lung metastasis. The decision was to proceed with resection through a transabdominal and perineal incision, even in the presence of metastasis since it's a very slow growing tumor with long life expectancy. The pathology was consistent with aggressive angiomyxoma. 90% of patients with angiomyxoma are women. Although it is benign, the tumor is still aggressive because of the high rate of local recurrence after resection. Angiomyxoma is a mesenchymal tumor, composed of fibroblasts within a myxoid background. Treatment is usually through wide local excision to achieve an R0 resection. Our approach was through a transabdominal and perineal incision, which allowed full control and mobilization of the tumor without disrupting the capsule. This surgical approach was not described previously in the literature. The principle to achieve cure in aggressive angiomyxoma is by optimizing exposure through two different incisions, wide excision while keeping the capsule intact and removing enbloc any invaded organ.


Penetrating atherosclerotic ulcer of the descending thoracic aorta: treatment by endovascular stent-graft.
To present four cases of penetrating ulcer of the descending thoracic aorta treated by transfemoral insertion of an endoluminal stent-graft. Four patients with penetrating aortic ulcers were reviewed. Three cases were complicated by rupture, false aneurysm, or retrograde dissection. All patients were treated by endovascular stent-graft and were followed by helical computed tomography (CT). Endovascular stent-graft deployment was successful in all patients. However, in one case we observed a perigraft leak that spontaneously disappeared within the first month, and two interventions were needed for another patient. Following treatment, one episode of transient spinal ischemia was observed. The 30-day survival rate was 100%, but one patient died from pneumonia with cardiac failure 34 days after the procedure. In one patient, helical CT performed at 3 months showed a false aneurysm independent of the first ulcer. This patient refused any further treatment and suddenly died at home (unknown cause) after a 6-month follow-up period. Transluminal placement of endovascular stent-grafts for treatment of penetrating ulcers of the descending thoracic aorta appears to be a possible alternative to classical surgery. After treatment, follow-up by CT is essential to detect possible complications of the disease.


Proteome reveals the mechanism of selenium-sulfur interaction in regulating isothiocyanate biosynthesis and the physiological metabolism of broccoli sprouts.
Broccoli sprouts have a strong ability to accumulate isothiocyanate and selenium. In this study, the isothiocyanate content increased significantly as a result of ZnSO4 stress. Particularly, based on the isothiocyanate content is not affected, the combined ZnSO4 and Na2SeO3 treatment alleviated the inhibition of ZnSO4 and induced selenium content. Gene transcription and protein expression analyses revealed the changes in isothiocyanate and selenium metabolite levels in broccoli sprouts. ZnSO4 combined with Na2SeO3 was proven to activate a series of isothiocyanate metabolite genes (UGT74B1, OX1, and ST5b) and selenium metabolite genes (BoSultr1;1, BoCOQ5-2, and BoHMT1). The relative abundance of the total 317 and 203 proteins, respectively, in 4-day-old broccoli sprouts varied, and the metabolic and biosynthetic pathways for secondary metabolites were significantly enriched in ZnSO4/control and ZnSO4 combined Na2SeO3/ZnSO4 comparisons. The findings demonstrated how ZnSO4 combined with Na2SeO3 treatment reduced stress inhibition and the accumulation of encouraged selenium and isothiocyanates during the growth of broccoli sprouts.


Horizontal cells of the turtle retina. I. Light microscopy of Golgi preparations.
In Golgi preparations of turtle retina, four types of horizontal cells were observed and their morphological characteristics determined in vertical thick sections, whole mount preparations, and reconstructions from serial 1-micrometer sections. H1 consists of a nucleated, stellate cell body (H1CB) and an irregular, tuberous axon terminal (H1AT) connected by a slender axon. Both parts of these cells make contact with receptor cells. H1CB's appear to correspond to "L2-type cells" while H1AT's correspond to "L1-type cells" described in the physiological literature. H2 and H3 are axonless stellate cells which are similar to one another in vertical profile and may occasionally appear similar in horizontal view. In general, the dendritic tree is more densely branched and the density of receptor cell contacts is higher for H2 than for H3. H2-type cells may correspond to "R/G C-type cells." H4 is also an axonless stellate cell type which is smaller than H2 or H3 at equivalent retinal locations. The dendritic fields of H1CB's vary widely, but systematically, in size and shape over the retina. Their size is inversely related to receptor cell density, and the shape of the dendritic tree varies from roughly circular in the central area to elliptical in the periphery of the retina.


Binding mechanism of lipase to Ligupurpuroside B extracted from Ku-Ding tea as studied by multi-spectroscopic and molecular docking methods.
The interaction of lipase with Ligupurpuroside B was studied by multiple spectroscopic techniques, enzyme activity and molecular modeling under simulative physiological condition. According to Stern-Volmer equation, fluorescence of lipase was quenched by Ligupurpuroside B via a static quenching mechanism because of formation of Ligupurpuroside B-lipase complex. Binding constants, number of binding sites & thermodynamic parameters were evaluated. The values of ΔGo (-25.085 kJ mol-1), ΔHo (-12.14 kJ mol-1) and ΔSo (+43.45 J mol-1 K-1) at 298 K indicated that Ligupurpuroside B-lipase interaction is spontaneous and hydrophobic interaction is the main force stabilizing the Ligupurpuroside B-lipase complex. The enzyme activity assay showed that Ligupurpuroside B inhibited lipase activity efficiently. Synchronous fluorescence spectra (SFS) suggested that Ligupurpuroside B is closer to Trp residues than to Tyr residues. All above experimental results were confirmed by molecular docking studies, which further indicated the binding site of Ligupurpuroside B on the surface of lipase, and the amino acid residues of lipase interacting with Ligupurpuroside B. Our present research work gives valuable information on the design of drugs with lipase as a carrier and should be useful for food industries.


Effects of alcohol on pericardial adhesion formation in hypercholesterolemic swine.
Reoperative cardiac surgery is complicated in part because of extensive adhesions encountered during the second operation. The purpose of this study was to examine the effects of alcohol with and without resveratrol (red wine vs vodka) on postoperative pericardial adhesion formation in a porcine model of hypercholesterolemia and chronic myocardial ischemia. Male Yorkshire swine were fed a high-cholesterol diet to simulate conditions of coronary artery disease followed by surgical placement of an ameroid constrictor to induce chronic ischemia. Postoperatively, control pigs continued their high-cholesterol diet alone, whereas the 2 experimental groups had diets supplemented with red wine or vodka. Seven weeks after ameroid placement, all animals underwent reoperative sternotomy. Compared with controls, pericardial adhesion grade was markedly reduced in the vodka group, whereas there was no difference in the wine group. Intramyocardial fibrosis was significantly reduced in the vodka group compared with controls. There was no difference in expression of proteins involved in focal adhesion formation between any groups (focal adhesion kinase, integrin alpha-5, integrin beta-1, paxillin, vinculin, protein tyrosine kinase 2, protein kinase C ε, and phosphorylated protein kinase C ε). The wine group exhibited elevated C-reactive protein levels versus the control and vodka groups. Postoperative vodka consumption markedly reduced the formation of pericardial adhesions and intramyocardial fibrosis, whereas red wine had no effect. Analysis of protein expression did not reveal any obvious explanation for this phenomenon, suggesting a post-translational effect of alcohol on fibrous tissue deposition. The difference in adhesion formation in the vodka versus wine groups may be due to increased inflammation in the wine group.


Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone.
Many patients with chronic hepatitis B (CHB) do not meet the definitions of the traditional natural phases and are classified as being in the grey zone (GZ). To investigate liver histology, and to establish a management strategy for patients with CHB in the GZ. This study included 1043 patients with CHB who underwent liver biopsy. Phases of natural history were determined according to the AASLD 2018 hepatitis B guidance. CHB patients in the GZ were divided into HBeAg-positive, normal ALT and HBV DNA ≤106 IU/ml (GZ-A); HBeAg-positive, elevated ALT and HBV DNA ≤2 × 104 IU/ml (GZ-B); HBeAg-negative, normal ALT and HBV DNA ≥2 × 103 IU/ml (GZ-C) and HBeAg-negative, elevated ALT and HBV DNA ≤2 × 103 IU/ml (GZ-D). Significant histological disease was defined as liver inflammation ≥G2 and/or liver fibrosis ≥S2. Two hundred and forty two (23.2%) patients were in the GZ. Approximately 72.7% had significant histological disease. HBeAg-positive GZ CHB patients had a higher proportion of significant histological disease than HBeAg-negative GZ patients (91.1% vs. 68.5%, p = 0.002). GZ-D (42.6%) was the dominant category, followed by GZ-C (38.8%), GZ-A (10.3%) and GZ-B (8.3%). The highest proportion of significant histological disease was observed patients in GZ-B (100.0%), followed by GZ-A (84.0%), GZ-D (69.9%) and GZ-C (67.0%). Prothrombin time (PT) was an independent risk factor of significant histological disease in the HBeAg-negative GZ. Over 70% of GZ CHB patients had significant histological disease. We recommend antiviral treatment for HBeAg-positive and HBeAg-negative GZ CHB patients with high PT.


Seminal vesiculitis.
Although accurate diagnosis of seminal vesiculitis still seems to be a problem, the disease can be treated surgically if the value of the animal warrants. Although this technique offers superior surgical exposure and seems to be successful in young bulls, its value in adult bulls is still questionable. There have been no reports of successful seminal vesiculectomy in aged bulls of which the authors are aware.


Improving sampling of crystallographic disorder in ensemble refinement.
Ensemble refinement, the application of molecular dynamics to crystallographic refinement, explicitly models the disorder inherent in macromolecular structures. These ensemble models have been shown to produce more accurate structures than traditional single-model structures. However, suboptimal sampling of the molecular-dynamics simulation and modelling of crystallographic disorder has limited the utility of the method, and can lead to unphysical and strained models. Here, two improvements to the ensemble refinement method implemented within Phenix are presented: DEN restraints, which guide the local sampling of conformations and allow a more robust exploration of local conformational landscapes, and ECHT disorder models, which allow the selection of more physically meaningful and effective disorder models for parameterizing the continuous disorder components within a crystal. These improvements lead to more consistent and physically interpretable simulations of macromolecules in crystals, and allow structural heterogeneity and disorder to be systematically explored on different scales. The new approach is demonstrated on several case studies and the SARS-CoV-2 main protease, and demonstrates how the choice of disorder model affects the type of disorder that is sampled by the restrained molecular-dynamics simulation.


Reversible and irreversible intracellular Ca2+ spiking in single isolated human platelets.
1. We have developed conditions that permit long duration recordings of [Ca2+]i in single, isolated human platelets and studied the reversibility of Ca2+i spiking following activation by physiological and artificial stimuli. 2. Fura-2-loaded platelets were immobilized at the tip of a saline-filled glass pipette using gentle suction. 'Contact' activation of Ca2+i spiking was observed in a proportion (11 %) of platelets, which continued for the duration of each recording (range 8-45 min). 3. Platelets that displayed constant, resting Ca2+i levels were used to test the effects of agonists. ADP (10 microM) increased [Ca2+]i in the form of either one to two spikes followed by an elevated plateau level (60 % of cells) or multiple Ca2+ spikes of irregular amplitude (40 % of cells). ADP-induced Ca2+i mobilization was completely reversible and repeatable. 4. Thrombin (1 u ml-1) evoked Ca2+i spiking in the majority (88 %) of platelets tested, which was not inhibited by perfusion of agonist-free saline throughout the recording period (range 8-67 min). 5. The clear difference in the reversibility of activation by different stimuli may reflect the distinct roles of individual agonists in haemostasis and have important consequences in the design of treatments for thrombosis.


[Reforms of practical medicine in the period of the first scientific revolution ( XVII century - 70-ies of XVIII century). Communication 2. Development and introduction of new therapeutic-diagnostic concept].
Reforms in practical medicine in the course of the first scientific revolution are described. This period indicates a rise of a principally novel therapeutic-diagnostic conception. Main lines of this conception are presented and consequences of its introduction are analysed.


Amplified multiplexed analysis of DNA by the exonuclease III-catalyzed regeneration of the target DNA in the presence of functionalized semiconductor quantum dots.
Quantum dots (QDs) functionalized with a black-hole quencher are used as optical tracer for the detection of DNA using exonuclease as a biocatalyst. The binding of the target DNA or of a target/open hairpin complex to the functionalized QDs leads to the exonuclease-stimulated recycling of the target DNA or the target/hairpin complex. This results in the triggering of the luminescence of the QDs that provides a readout signal for the amplified sensing process. By using different-sized QDs, the multiplexed detection of DNAs is demonstrated.


The Incidence and Predisposing Factors of John Cunningham Virus-Induced Progressive Multifocal Leukoencephalopathy in Southern Finland: A Population-Based Study.
The aim of this study was to assess the prevalence, incidence rate (IR), predisposing factors, survival rate, and diagnostic delay of progressive multifocal leukoencephalopathy (PML) across medical specialties. Another objective was to survey how PML diagnosis was made in the studied cases. This is a cross-sectional retrospective observational study of PML cases across different medical specialties during 2004-2016 in the Finnish Capital Region and Southern Finland. Data were obtained from clinical records, clinical microbiology, pathology and radiology department records, and human immunodeficiency virus (HIV) quality register medical records. A total of 31 patients were diagnosed with PML. The prevalence of PML was 1.56 per 100 000 people and the IR was 0.12 per 100 000 individuals per year during 2004-2016. Hematologic malignancies (n = 19) and HIV/acquired immune deficiency syndrome (n = 5) were the most common underlying diseases, and all patients who had malignant diseases had received cancer treatment. Before PML diagnosis, 21 (67.7%) patients were treated with chemotherapy, 14 (45.2%) patients with rituximab, and 1 patient (3.2%) with natalizumab. Two patients (6.5%) had no obvious immunocompromising disease or treatment. Neither gender, age, first symptoms, previous medication, nor underlying disease influenced the survival of PML patients significantly. The 5-year survival rate was poor, at less than 10%. The majority of PML patients in our study had a predisposing disease or had immunosuppressive or monoclonal antibody therapy. In the future, broader use of immunosuppressive and immunomodulatory medications may increase incidence of PML among patients with diseases unassociated with PML. Safety screening protocols for John Cunningham virus and PML are important to prevent new PML cases.


Contagion in stress. An infectious disease model for posttraumatic stress in children.
Posttraumatic stress responses involve the development of characteristic symptoms of reexperiencing, arousal, and avoidance following exposure to a traumatic event. This article uses an infectious disease model to describe exposure and transmission of posttraumatic stress responses, individual susceptibility and resilience, onset of symptoms, and prevention and control.


Enhancement of in vitro binding and some of the pharmacological properties of diazepam by a novel anthelmintic agent, Avermectin B1a.
A novel macrocyclic lactone disaccharide anthelmintic agent, Avermectin B1a (AVM) has been found to cause a concentration-dependent increase in the in vitro binding of 3H-diazepam to rat and mouse brain membranes. The increase in binding is manifested as both an increase in the affinity and number of bindings sites for 3H-diazepam. Preliminary in vivo studies demonstrate that AVM can also enhance some of the pharmacological actions of diazepam.


A Label-Free Photoluminescence Genosensor Using Nanostructured Magnesium Oxide for Cholera Detection.
Nanomaterial-based photoluminescence (PL) diagnostic devices offer fast and highly sensitive detection of pesticides, DNA, and toxic agents. Here we report a label-free PL genosensor for sensitive detection of Vibrio cholerae that is based on a DNA hybridization strategy utilizing nanostructured magnesium oxide (nMgO; size >30 nm) particles. The morphology and size of the synthesized nMgO were determined by transmission electron microscopic (TEM) studies. The probe DNA (pDNA) was conjugated with nMgO and characterized by X-ray photoelectron and Fourier transform infrared spectroscopic techniques. The target complementary genomic DNA (cDNA) isolated from clinical samples of V. cholerae was subjected to DNA hybridization studies using the pDNA-nMgO complex and detection of the cDNA was accomplished by measuring changes in PL intensity. The PL peak intensity measured at 700 nm (red emission) increases with the increase in cDNA concentration. A linear range of response in the developed PL genosensor was observed from 100 to 500 ng/μL with a sensitivity of 1.306 emi/ng, detection limit of 3.133 ng/μL and a regression coefficient (R(2)) of 0.987. These results show that this ultrasensitive PL genosensor has the potential for applications in the clinical diagnosis of cholera.


Public health workforce: challenges and policy issues.
This paper reviews the challenges facing the public health workforce in developing countries and the main policy issues that must be addressed in order to strengthen the public health workforce. The public health workforce is diverse and includes all those whose prime responsibility is the provision of core public health activities, irrespective of their organizational base. Although the public health workforce is central to the performance of health systems, very little is known about its composition, training or performance. The key policy question is: Should governments invest more in building and supporting the public health workforce and infrastructure to ensure the more effective functioning of health systems? Other questions concern: the nature of the public health workforce, including its size, composition, skills, training needs, current functions and performance; the appropriate roles of the workforce; and how the workforce can be strengthened to support new approaches to priority health problems.The available evidence to shed light on these policy issues is limited. The World Health Organization is supporting the development of evidence to inform discussion on the best approaches to strengthening public health capacity in developing countries. WHO's priorities are to build an evidence base on the size and structure of the public health workforce, beginning with ongoing data collection activities, and to map the current public health training programmes in developing countries and in Central and Eastern Europe. Other steps will include developing a consensus on the desired functions and activities of the public health workforce and developing a framework and methods for assisting countries to assess and enhance the performance of public health training institutions and of the public health workforce.


Transection of the bladder as a method of treatment in adult enuresis nocturna.
Ten adults with enuresis were treated by bladder transection. Urodynamic assessment was carried out before and after the operation. No significant urodynamic changes were recorded following transection. However, good results were obtained in 5 cases and improvement in 2.


A maize heat shock factor ZmHsf11 negatively regulates heat stress tolerance in transgenic plants.
Heat shock transcription factors (Hsfs) are highly conserved among eukaryote and always play vital role in plant stress responses. Whereas, function and mechanism of Hsfs in maize are limited. In this study, an HSF gene ZmHsf11, a member of class B Hsfs, was cloned from maize, and it was up-regulated under heat treatment. ZmHsf11 was a nuclear protein with no transcriptional autoactivation activity in yeast. Overexpression of ZmHsf11 gene in Arabidopsis and rice significantly reduced the survival rate under heat shock treatment and decreased ABA sensitivity of transgenic plants. Under heat stress, transgenic rice accumulated more H2O2, increased cell death, and decreased proline content compared with wild type. In addition, RT-qPCR analysis revealed that ZmHsf11 negatively regulated some oxidative stress-related genes APX2, DREB2A, HsfA2e, NTL3, GR and HSP17 under heat stress treatment. Our results indicate that ZmHsf11 decreases plant tolerance to heat stress by negatively regulating the expression of oxidative stress-related genes, increasing ROS levels and decreasing proline content. It is a negative regulator involved in high temperature stress response.


Assessment of body composition of male patients with type 2 diabetes by bioelectrical impedance analysis.
Type 2 diabetes is a metabolic disorder and as such should affect the components of body composition of diabetics. The changes it induces in patients complement the anthropological characteristics of this disease. The AIM of the present study was to assess the effect type 2 diabetes has on some of the body composition components in male diabetics. The study included 169 male patients with type 2 diabetes. All patients (ethnical Bulgarian) were allocated into two age groups: group 1--patients aged 40-60 years and group 2--patients aged 61-80 years. Direct measurements of parameters were performed with a Tanita body composition analyser. The bioimpedance parameters we measured were body fat percentage (%BF), total body water percentage (%TBW), muscle mass (MM), bone mass (BM), and visceral fat (VF). The derived parameters were total body fat (TBF) (kg), active body mass (ABM) (kg), active body mass percentage. Body composition of male diabetics aged 40-60 years: %BF, VF and TBF were statistically significantly higher in diabetics than in healthy controls. Body composition of male diabetic patients aged 61-80 years: BM and VF were significantly higher in diabetic patients than in controls. %BF and MM did not have a high statistical significance. Inter-age comparison of body composition in male diabetics: we found that %BF, %TBW, MM and BM tend to be higher in 40-60-year-olds. Visceral fat was increased in the 61-80-year-olds, the difference reaching high statistical significance. Bioimpedance analysis (BIA) of body composition showed the total body fat in male diabetics of both age groups to be greater than that in controls. TBF was greater in the younger age group at the expense of the subcutaneous fat, while in the more elderly patients it was the visceral fat that was increased, which makes their body composition correlate rather adversely with the prognosis, course and outcome of the disease. The relative percentage of active body mass was greater in the healthy individuals than in diabetic patients. This parameter was higher in the younger age group of diabetic patients than in the more elderly patients; this finding is probably due to the longer duration of the disease and also to aging changes such as osteoporosis, muscle atrophy and decreased quantities of body water.


Oxidation-induced aggregation of LDL increases their uptake by smooth muscle cells from human aorta.
Oxidative modification of human blood LDL induced by Cu2+, NaOCl, or 2,2-azobis-(2-aminopropane hydrochloride) was followed by their partial aggregation. Separation of oxidized LDL into aggregates and nonaggregated particles showed that they are characterized by a similar degree of oxidative modification. In contrast to nonaggregated particles, LDL aggregates in the same concentration significantly increased cholesterol content in smooth muscle cells from the intact (no involoved in atherosclerosis) human aortic intima. Our results indicate that atherogenicity of LDL oxidized by various factors is mainly associated with the formation of aggregates, but does not depend on the degree of oxidative modification.


Ca2+-dependent phosphorylation by endogenous kinases of Mr 95 K and 50 K-55 K proteins in PC12 pheochromocytoma cells.
Endogenous protein phosphorylation of PC12 cells was investigated with the homogenate as well as intact cells. In the case of the homogenate, the major proteins that were phosphorylated in the presence of Ca2+ were found to be of Mr 95 K and Mr 50 K-55 K. Ca2+/calmodulin-dependent protein kinase appeared to be responsible for phosphorylation of Mr 50 K-55 K proteins and partly of Mr 95 K protein. The apparent Km's for Ca2+ of Mr 95 K and 50 K-55 K protein phosphorylation were 2.2 x 10(-7) M and around 1.5 x 10(-6) M, respectively. Since several cell lines of neuroblastoma exhibited Mr 95 K protein phosphorylation of similar type, the protein phosphorylation may be a common process shared by neuronal cells. Depolarization of intact PC12 cells by high K+ concentrations induced Mr 95 K protein phosphorylation. The results suggest that a physiological increase by excitation in the intracellular Ca2+ concentration triggers phosphorylation of Mr 95 K protein in neuronal cells and this phosphorylation may play a role in the regulation of transmitter release.


Variations in the activity of nucleolar organizers in different tissues, demonstrated by silver staining of human normal and leukemic cells.
A simple silver-staining technique that demonstrates those nucleolar organizing regions of metaphase chromosomes which are transcriptionally active during the preceding interphase (AgNORs) has been applied to cells obtained from the bone marrow and mitogen-stimulated peripheral blood lymphocyte cultures of hematologically normal individuals and patients with various forms of leukemia. In the majority of bone marrow cells from the normal controls and many of the patients, the number of cells with detectable AgNORs, and the staining intensities in those cells which were Ag+, were markedly reduced compared with the levels found in blood lymphocytes. The numbers of cells having satellite associations and the numbers of chromosomes participating in these associations also generally reflected the proportions of AgNORs present. When patterns of bone marrow silver staining were compared between patients with leukemia, distinct differences were found which could be correlated with cytology. It is suggested that different cell types have characteristic AgNOR staining profiles, reflecting specific regulation of ribosomal RNA synthesis in particular cell lineages. AgNOR staining may indicate, therefore, the predominant cell types that divide in the bone marrows of patients with different forms of leukemia.


Non-conscious prediction and a role for consciousness in correcting prediction errors.
As a result of the evolutionary pressure for survival, the brain relies on a number of non-conscious predictive neural mechanisms which allow for rapid, efficient behavioral responses to the environment. These predictive mechanisms enable the brain to recognize objects by sampling just a few sensory inputs, to anticipate what events are likely to occur and to prepare a response before events actually occur. Consciousness appears to play a role in the detection and correction of prediction errors. The author, a psychotherapist and psychoanalyst, proposes that this monitoring or oversight function of consciousness can be used to understand how conscious awareness facilitates change in the psychotherapeutic treatment of patients who repeat maladaptive patterns of behavior.


The effect of intravenous golimumab on health-related quality of life and work productivity in adult patients with active ankylosing spondylitis: results of the phase 3 GO-ALIVE trial.
The effect of intravenous (IV) golimumab on health-related quality of life (HRQoL) and productivity in patients with ankylosing spondylitis (AS) was evaluated. Patients were randomized to IV golimumab 2 mg/kg (n = 105) at weeks 0, 4, then every 8 weeks (q8w) through week 52 or placebo (n = 103) at weeks 0, 4, 12, with crossover to golimumab 2 mg/kg at weeks 16, 20, then q8w through week 52. Changes from baseline in EuroQol-5 dimension-5 level (EQ-5D-5L) index and visual analog scale (EQ-VAS), daily productivity VAS, Work Limitations Questionnaire (WLQ), and Ankylosing Spondylitis Quality of Life (ASQoL) were assessed. Correlations between these outcomes and disease activity and patient functioning outcomes were evaluated post hoc. At week 16, changes from baseline (mean ± standard deviation) in EQ-5D-5L index (0.17 ± 0.16 vs 0.05 ± 0.14), EQ-VAS (20.3 ± 24.6 vs 4.8 ± 23.5), daily productivity VAS (- 2.9 ± - 2.9 vs - 1.1 ± - 2.5), WLQ productivity loss score (- 3.5 ± - 5.3 vs - 1.9 ± - 4.0), and ASQoL (- 5.4 ± - 5.0 vs - 1.8 ± - 4.5) were greater in the IV golimumab versus placebo group, respectively. At week 28, changes from baseline were similar between the IV golimumab and placebo-crossover groups (EQ-5D-5L index: 0.18 ± 0.17 and 0.16 ± 0.16, EQ-VAS: 20.5 ± 27.9 and 22.5 ± 23.1, daily productivity VAS: - 3.1 ± - 3.0 and - 3.1 ± - 2.8, WLQ productivity loss: - 3.9 ± - 5.5 and - 4.5 ± - 4.5, and ASQoL: - 5.3 ± - 5.2 and - 5.3 ± - 4.8, respectively); improvements were maintained through week 52. HRQoL and productivity outcomes were generally moderately correlated with disease activity and functioning outcomes. In patients with AS, IV golimumab produced sustained improvements in HRQoL and productivity through 1 year, which correlated with improvements in disease activity and functioning. ClinicalTrials.gov registry number is NCT02186873. Key Points • Intravenous (IV) golimumab resulted in clinically important improvement in general and ankylosing spondylitis-specific health-related quality of life (HRQoL) and productivity outcomes in patients with ankylosing spondylitis (AS) as early as week 8 and maintained improvement through 1 year • Improvements in HRQoL and productivity outcomes in these patients with AS were correlated with improvements in measures of disease activity and patient functional capability • IV golimumab is an effective treatment option for AS that can help mitigate the negative effects of the disease on HRQoL and productivity.


Structural analysis and chemical depolymerization of the capsular polysaccharide of Streptococcus pneumoniae type 1.
NMR spectroscopy can be used to characterize bacterial polysaccharides such as that of Streptococcus pneumoniae type 1 which is a component of the 23-valent pneumococcal vaccine in clinical use. This particular polysaccharide gives NMR spectra with wide lines apparently due to restricted molecular mobility and chain flexibility which leads to rapid dipolar T(2) relaxation limiting the possibility of detailed spectral analysis. Removal of O-acetyl groups found on approximately two thirds of the repeating subunits of pneumococcal type 1 capsule leads to narrower NMR lines facilitating a complete assignment of the 1H and 13C NMR spectra. Degradation of the polysaccharide by periodate oxidation followed by base treatment leads to an oligosaccharide fragment of approximately three repeating trisaccharide units. This oligosaccharide has narrow NMR lines and 1H and 13C assignments very similar to those of the O-deacetylated polysaccharide. In the native polysaccharide, O-acetyl groups are located on the 2- and 3-positions of the 4-linked galacturonic acid residue providing protection against periodate oxidation. Analysis of NOESY spectra combined with molecular modeling of the oligosaccharide shows that flexibility occurs in certain of the saccharide linkages.


End-cap modeling on the thienyl-substituted benzodithiophene trimer-based donor molecule for achieving higher photovoltaic performance.
Despite the substantial advancements in organic solar cells (OSCs), the best devices still have quite low efficiencies due to less focus on donor molecules. With the intention to present efficient donor materials, seven small donor molecules (T1-T7) were devised from DRTB-T molecule by using end-capped modeling. Newly designed molecules exhibited remarkable improved optoelectronic properties such as less band gap (from 2.00 to 2.23 eV) than DRTB-T having band gap of 2.57 eV. Similarly, a significant improvement in λmax values was noticed in designed molecules in gaseous medium (666 nm-738 nm) and solvent medium (691 nm-776 nm) than DRTB-T having λmax values at 568 nm and 588 nm in gas and solvent phase respectively. Among all molecules, T1 and T3 exhibited significant improvement in optoelectronic properties such as narrow band gap, lower excitation energy, higher λmax values and lower electron reorganization energy as compared to pre-existed DRTB-T molecule. The better functional ability of T1-T7 is also suggested by an improvement in open circuit voltage (Voc) of designed structures (1.62 eV-1.77 eV) as compared to R (1.49 eV) when PC61BM is used as an acceptor. So, all our newly derived donors can be employed in the active layer of organic solar cells to manufacture efficient OSCs.


Quantitative basic residue requirements in the cleavage-activation site of the fusion glycoprotein as a determinant of virulence for Newcastle disease virus.
Newcastle disease virus exhibits a wide range of pathogenicity and virulence which, as with all paramyxoviruses, is directly related to the cleavability of a precursor (F0) of the fusion glycoprotein by cellular proteases. Sequence analyses of the cleavage site of several virulent and avirulent isolates of the Newcastle disease virus serotype reveal a correlation between virulence or pathogenicity and a high content of basic amino acid residues at the cleavage site. A similar correlation has been seen for other paramyxoviruses.


Combined presence of coronary artery ectasia and descending aortic dissection in polycystic kidney disease presenting as acute coronary syndrome.
We report the unusual case of a 55-year-old man with a history of hypertension and dyslipidemia who presented with acute coronary syndrome. Examination revealed that he had coronary artery ectasia and descending aortic dissection along with polycystic kidney disease.


Sensitivity of a helical diode array device to delivery errors in IMRT treatment and establishment of tolerance level for pretreatment QA.
The aim of this study is to determine the gantry angle and multileaf collimator (MLC) gap error-detection threshold of a diode helical array with an inserted micro-ionization chamber in order to use this device for the pretreatment quality assurance (QA) of intensity-modulated radiation therapy (IMRT) treatments. Implications on the dose-volume histograms (DVHs) of the patient treatments will also be considered for the establishment of a QA protocol with a reasonable tolerance level. Three dynamic IMRT HN (head and neck) and prostate treatments were studied. Random and systematic variations of gantry angle and systematic errors in MLC gap width of the clinical treatments were analyzed in order to establish the detection sensitivity of the array. The associated clinical significance was studied introducing the same errors in the treatment plan based on the patients' computed tomography (CT) and calculating the corresponding DVHs. The Gamma (3%/3 mm) presented a 4% variation in failure rate for a rotation error of 1° for both types of treatment. Both systematic and random errors in gantry rotation angle have little effect on the patients' DVHs. MLC gap width errors of 1 mm and 2 mm in the prostate treatments imply a mean variation in isocenter-measured absorbed dose of 2.1% and 4.1%, respectively. In the case of HN, these errors entail a change in measured isocenter dose of 4.7% and 8.6%, respectively. The variation observed in the DVHs of the patients was, basically, a global displacement of the curves proportional to the isocenter dose variation caused by the gap width error. According to the array sensitivity to the analyzed errors and its implication in patient DVHs, a tolerance of 95% point passing rate for the gamma criterion 3%/2 mm and an agreement of 2% in isocenter absolute dose have been established as tolerance criteria for our pretreatment IMRT QA protocol.


Risk and benefit of additional aortocoronary bypass grafting in patients undergoing cardioverter-defibrillator implantation.
It is unclear whether additional aortocoronary bypass grafting should be performed in patients who need an automatic implantable cardioverter defibrillator (ICD) in one- or two-step procedures. Therefore we studied the follow-up of 139 patients who underwent epicardial implantation of the cardioverter defibrillator (CD). All patients had coronary artery disease and recurrent ventricular tachycardia or fibrillation. Eighty-nine patients had implantation of the CD without additional surgical approaches (group G1), and 50 patients had concomitant aortocoronary bypass grafting (group G2). Perioperative mortality (within 30 days after CD implant) was 1 (1%) of 89 patients in G1 and 6 (12%) of 50 patients in G2 (p < 0.01). During the mean follow-up of 26 +/- 20 months, sudden death occurred in four (4%) of 89 patients in G1 and two (4%) of 50 patients in G2. Twenty-three (17%) patients died of cardiac failure (18 [20%] patients in G1 and 5 [10%] patients in G2). ICD discharges occurred in 69 (78%) of 89 patients in G1 and in 36 (72%) of 50 patients in G2. The mean incidence of ICD discharges was 23 +/- 69 shocks per patient in G1 and 18 +/- 25 shocks per patient in G2 (p = NS). We conclude that concomitant aortocoronary bypass grafting during CD implantation leads to a higher perioperative mortality. Avoidance of myocardial ischemia does not significantly influence sudden death mortality nor markedly reduce the number of ICD discharges.


Geographic variation in gorilla limb bones.
Gorilla systematics has received increased attention over recent decades from primatologists, conservationists, and paleontologists. Studies of geographic variation in DNA, skulls, and teeth have led to new taxonomic proposals, such as recognition of two gorilla species, Gorilla gorilla (western gorilla) and Gorilla beringei (eastern gorilla). Postcranial differences between mountain gorillas (G. beringei beringei) and western lowland gorillas (G. g. gorilla) have a long history of study, but differences between the limb bones of the eastern and western species have not yet been examined with an emphasis on geographic variation within each species. In addition, proposals for recognition of the Cross River gorilla as Gorilla gorilla diehli and gorillas from Tshiaberimu and Kahuzi as G. b. rex-pymaeorum have not been evaluated in the context of geographic variation in the forelimb and hindlimb skeletons. Forty-three linear measurements were collected from limb bones of 266 adult gorillas representing populations of G. b. beringei, Gorilla beringei graueri, G. g. gorilla, and G. g. diehli in order to investigate geographic diversity. Skeletal elements included the humerus, radius, third metacarpal, third proximal hand phalanx, femur, tibia, calcaneus, first metatarsal, third metatarsal, and third proximal foot phalanx. Comparisons of means and principal components analyses clearly differentiate eastern and western gorillas, indicating that eastern gorillas have absolutely and relatively smaller hands and feet, among other differences. Gorilla subspecies and populations cluster consistently by species, although G. g. diehli may be similar to the eastern gorillas in having small hands and feet. The subspecies of G. beringei are distinguished less strongly and by different variables than the two gorilla species. Populations of G. b. graueri are variable, and Kahuzi and Tshiaberimu specimens do not cluster together. Results support the possible influence of higher-altitude Pleistocene refugia on patterns of geographic variation in gorillas.


The West African Ebola emergency and reconstruction; lessons from Public Health England.
West African governments, the WHO and wider international community were caught unprepared for the world's largest Ebola outbreak of 2014-16. This was an unprecedented challenge to local services and international agencies, since the emergency required high-tech molecular diagnostic services operated by specialist staff and a coordinated emergency response in addition to humanitarian support, which was not available at the beginning of the outbreak. Public Health England (PHE), as a new national public health agency was well placed to provide support for these needs. After the outbreak, PHE supported reconstruction to ensure diagnostic and emergency planning capability remained in place in the immediate aftermath of the outbreak and build necessary public health infrastructure for the future. The article describes the role PHE played as a national public health agency supporting reconstruction and long-term development through the UK Government (Department for International Development) programme called 'Resilient Zero'. Public Health England (PHE), UK Government's Department for International Development, WHO, US Centers for Communicable Diseases (CDC), China Centre for Communicable Diseases (China CDC). The need for reliable, sustainable, in country molecular diagnostics, together with a programme to strengthen in country Emergency Planning, Preparedness and Response (EPRR). Providing high tech molecular capability in a resource-poor West African country with variable provision of basic diagnostic equipment, intermittent power supply, ineffective supply chains and maintaining training capacity for emergency planning in the long term. Emergency planning models from the West needed to be adapted for the countries' context. Short term aid projects as a model did not suite this development requirement. PHE had strong local and international political support to reconstruct three Government regional laboratories and deploy molecular technology. Significant learning by PHE as a national public health agency and sharing this will be of benefit to other national public health agencies. UK staff reported increased levels of satisfaction and experience relevant to public health practice. The Sierra Leonean Government and officials requested long-term levels of commitment. It is important for agencies such as PHE to constantly learn, develop long-term institutional partnerships and play a bigger role with other similar agencies internationally. How best to support sustainable high-tech molecular technology in West Africa and modules for emergency planning relevant to the context; evidence for long term versus short-term support for highly complex diagnostic capabilities; relevance to maintaining individual country public health infrastructure to ensuring global health security; benefits of overseas work for employee of a national agency.


The effect of sizing on the in vitro hydrodynamic characteristics and leaflet motion of the Toronto SPV stentless valve.
We established an in vitro model to investigate the effects of valve sizing on the hemodynamic characteristics and leaflet motion of the Toronto SPV valve (St Jude Medical, Inc, St Paul, Minn). Nine valves were first implanted in fresh porcine aortic roots and then retested in glutaraldehyde-treated porcine aortic roots. Three valves were 1- to 2-mm oversized, 3 were 1- to 2-mm undersized, and there were 3 size-for-size implantations. The elasticities of the aortic roots and the composite roots were measured in the pressure range between 0 and 120 mm Hg, and the composite roots were then tested in a pulsatile flow simulator. The transvalvular gradient and regurgitation were measured and the effective orifice area and performance index were calculated for each root. Leaflet motion was recorded on videotape. The external diameter of the fresh root increased by 35% as the hydrostatic pressure rose from 0 to 120 mm Hg, as compared with 11% for the glutaraldehyde-treated root. Valve implantation in the fresh root reduced the distensibility to 22% but did not change distensibility in the glutaraldehyde-treated root. The effective orifice area was dependent on the valve size, with the transvalvular gradient decreasing as the valve size increased. For the same size of valve the hydrodynamic parameters were slightly better if the valve was undersized by 1 mm. A significant difference in favor of the undersized valves was found in open-leaflet bending deformation. Leaflet motion of the stentless porcine aortic valve in vitro is improved if the valve is slightly undersized, and this may be beneficial to the long-term durability of the prosthesis.