Usher syndrome: definition and estimate of prevalence from two high-risk populations.
The Usher Syndrome (US) refers to the combined neurosensory deficits of profound hearing impairment and retinitis pigmentosa. We have obtained information on 600 cases of deaf-blindness from the registry of the Helen Keller National Center for Deaf-Blind Youths and Adults (HKNC). Of these, 54% met the diagnostic criteria of US, although only 23.8% were so diagnosed. More extensive analysis of 189 Usher clients from HKNC showed an excess of males, some variability in audiograms, and wide ophthalmologic variation. Genetic analysis of 113 sibships showed a segregation ratio consistent with recessive inheritance. The Acadian population of Louisiana has a high frequency of US which contributes significantly to the deaf population of the state. Among 48 cases from the Louisiana School for the Deaf, there was an excess of males, more variability in audiograms than expected, and an increased segregation ratio in the 26 informative sibships. Estimates of prevalence obtained using registry data and statistics from Louisiana clearly suggest that the previous estimate of 2.4 per 100,000 is too low for the United States. Recognizing problems with ascertainment, our prevalence estimate of 4.4 per 100,000 is still considered quite conservative.


The clinical impact of staging bone marrow examination on treatment decisions and prognostic assessment of lymphoma patients.
This study investigates the value of performing a staging bone marrow in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and classical hodgkin lymphoma (CHL). The results of 3112 staging bone marrow examinations were assessed for impact on prognostic assessment and critical treatment decisions. The detection of marrow involvement altered the disease-specific prognostic index for 4·3% of DLBCL, 6·2% of FL and 0·6% of CHL but marrow involvement in DLBCL was an independent prognostic factor. Knowing the marrow status potentially changed treatment in 92 patients, detection of these patients would have required 854 examinations to be performed.


Induction and augmentation of labor in hypertensive patients with intravenous prostaglandin E2.
Labor was successfully induced or stimulated with intravenous Prostaglandin E2 (0.1-2.0 microgram/min) in a group of twenty-nine hypertensive gravidae at 36-41 weeks' gestation. No adverse maternal or perinatal effects of the drug were recorded.


Enantioselective high-performance liquid chromatographic separations to study occurrence and fate of chiral pesticides in soil, water, and agricultural products.
As many as 40% of all plant protection products currently used contain chiral active ingredients. Enantiomers of the same pesticide have identical physicochemical properties in an isotropic medium, but they may display different activity and toxicity because of their interaction with enzymes or other naturally occurring asymmetric molecules. This difference may also lead to variations in biotic degradation rates, making one enantiomer more persistent than the other in natural and agricultural environments. In terms of methodological aspects, this critical review describes the most used chiral stationary phases for HPLC enantioseparations of chiral pesticides, pinpointing their strengths and weaknesses. As far as their applicability is concerned, most research has been carried out by means of columns based on derivatized amylose/cellulose due to their rather universal analyte coverage. The chromatographic compatibility with sensitive detection techniques, such as mass spectrometry, has allowed the trace analysis of stereoisomers, revealing ubiquitous occurrence of some chiral pesticides in surface waters, sediments, plants, agricultural soils, roots, fruit and vegetables. The study of their distribution and degradation in various environmental compartments and agricultural soil-plant systems has highlighted the enrichment with one enantiomer over the other in certain matrices following the enantioselective dissipation catalysed by microorganisms or plant enzymes as well as the phenomenon of chiral inversion in some cases. Irrespective of the reliability of a chiral method, such investigations are often hindered by the lack of pure standards of single enantiomers, which makes it difficult to identify their stereochemical configuration and requires precise strategies of quantification. Surely, the research in this field has been grown over the last few years due to the necessity of assessing and limiting risks related to exposure to chiral pesticides, which can be considered emerging contaminants in all aspects.


Minnesota Multiphasic Personality Inventory-2 revised form Symptom Validity Scale-Revised (MMPI-2-RF FBS-r; also known as Fake Bad Scale): psychometric characteristics in a nonlitigation neuropsychological setting.
This study examined fundamental psychometric characteristics of the Symptom Validity Scale-Revised (FBS-r) in a nonforensic sample of 303 neuropsychological referrals. FBS-r had a reliability (internal consistency) of .747 and two higher order factoral dimensions (Somatic Complaints and Optimism/Virtue). FBS-r had a discordant factor structure: Optimism/Virtue (7 items) was negatively related to Somatic Complaints (21 items) and undercut FBS-r measurement consistency (reliability). FBS-r scores, which purportedly reflect symptom exaggeration, are affected by as much as 23 T-score points on test items that are negatively related to symptom reporting. These data suggest that the FBS-r produces ambiguous scores reflecting two underlying dimensions that warrant additional research.


Definition and evaluation of a finite element model of the human heel for diabetic foot ulcer prevention under shearing loads.
Diabetic foot ulcers are triggered by mechanical loadings applied to the surface of the plantar skin. Strain is considered to play a crucial role in relation to ulcer etiology and can be assessed by Finite Element (FE) modeling. A difficulty in the generation of these models is the choice of the soft tissue material properties. In the literature, many studies attempt to model the behavior of the heel soft tissues by implementing constitutive laws that can differ significantly in terms of mechanical response. Moreover, current FE models lack of proper evaluation techniques that could estimate their ability to simulate realistic strains. In this article, we propose and evaluate a FE model of the human heel for diabetic foot ulcer prevention. Soft tissue constitutive laws are defined through the fitting of experimental stretch-stress curves published in the literature. The model is then evaluated through Digital Volume Correlation (DVC) based on non-rigid 3D Magnetic Resonance Image Registration. The results from FE analysis and DVC show similar strain locations in the fat pad and strain intensities according to the type of applied loads. For additional comparisons, different sets of constitutive models published in the literature are applied into the proposed FE mesh and simulated with the same boundary conditions. In this case, the results in terms of strains show great diversity in locations and intensities, suggesting that more research should be developed to gain insight into the mechanical properties of these tissues.


Proposing a novel care program: reminiscence therapy involved care for anxiety, depression, and quality of life in postoperative cervical cancer patients.
Reminiscence therapy (RT) relieves mental disorders and improves quality of life (QoL) in some cancer survivors, but in postoperative cervical cancer patients, its effect is unclear. This study aimed to assess the impact of reminiscence therapy involved care (RTIC) and usual care (UC) on anxiety, depression, QoL, and survival in postoperative cervical cancer patients. In this randomized control study, 152 eligible postoperative cervical cancer patients were randomized as 1:1 ratio into RTIC (N = 76) and UC (N = 76) groups: the former received routine care and RT, while the latter only received routine care for 12 months. Anxiety, depression, and QoL were evaluated from baseline (month (M) 0) to M12, respectively. Patients were continuously followed up to M36 for overall survival (OS) calculation. HADS-Anxiety score from M6 to M12 was decreased; both HADS-Depression score from M9 to M12 and depression rate at M12 were reduced in RTIC group compared with UC group (all P < 0.05). QLQ-C30 global health status score at M6 and M12, as well as QLQ-C30 function score at M12, was increased in RTIC group compared with UC group (all P < 0.05). However, QLQ-C30 symptom score at each visit and OS exhibited no difference between the two groups. From sub-group analysis, RTIC disclosed a distinct effect on patients whose age ≥ 50 years but not on those < 50 years. RTIC reduces anxiety (partly) and depression and improves QoL in postoperative cervical cancer patients, especially in old patients.


Evaluation of the antimicrobial activity and safety of Rhus vulgaris (Anacardiaceae) extracts.
Medicinal plants have been used in the treatment of various ailments in most developing countries. Oral infections are the most prevalent diseases in man. The Rhus family has been found to have antimicrobial, antimalarial, and anti-inflammatory properties. Few studies have been done on Rhus vulgaris Meikle. A study was conducted to determine the effect of Rhus vulgaris Meikle stem bark extracts against selected oral pathogenic microorganisms and the safety of the extracts in vitro and in vivo. Methanol:dichloromethane (1:1), methanol and aqueous extracts were tested for bacteriostatic and bactericidal effects against Methicillin Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Streptococcus mutans and Candida albicans. Cytotoxicity of the active extracts was determined using Vero E6 cell lines while safety was evaluated in mice and rats. Phytochemical screening was performed on the methanol extracts. One-way ANOVA and Tukey's multiple comparisons tests were performed using IBM SPSS statistics 20.0 for antimicrobial assay and acute toxicity testing. One-way ANOVA and Dunnett's multiple comparison tests were conducted using GraphPad Prism 8.0 for cytotoxicity assay. Methanol extract of Rhus vulgaris showed significant antimicrobial activity against MRSA (12.00 ± 0.00 mm; p-value of < 0.005; Minimum Inhibitory Concentration of 0.391 mg/ml; Minimum Bactericidal Concentration of 1.563 mg/ml). The extract were not cytotoxic at 100 μg/ml which was the highest tested concentration. In acute dermal irritation testing, the methanol extract resulted in mild irritation with erythema and flaking that cleared within 8 days. There were no observable adverse effects from oral administration of the extracts (acute oral toxicity testing) at concentrations of 50 mg/kg, 300 mg/kg and 2000 mg/kg. Tannins, saponins, flavonoids, terpenoids, glycosides, alkaloids and phenols were detected in the methanol extract. Antimicrobial activity of R. vulgaris extracts supports its traditional use as a toothbrush. Cytotoxicity demonstrated by the extracts as well as the mild skin irritation warrants further study before R. vulgaris can be recommended for the development of effective and safe mouthwashes.


Factors associated with immunization coverage of children in Assam, India: over the first year of life.
The children of Assam in the North-East Region of India have consistently evidenced low rates for routine childhood immunizations. This study has been conducted to evaluate the factors affecting the immunization coverage in the first year of life of the children. About 62.2% of the children were fully immunized. Lack of information among the parents was one of the major causes of drop out of vaccinations. The children from urban areas and mother's education level showed significant role in immunization coverage. Improvement in female literacy coupled with the reduction in the drop out rate would add to achieve a higher target of immunization among children in the study area.


Estimating non-genetic and genetic parameters of pre-weaning growth traits in Raini Cashmere goat.
Data and pedigree information used in the present study were 3,022 records of kids obtained from the breeding station of Raini goat. The studied traits were birth weight (BW), weaning weight (WW), average daily gain from birth to weaning (ADG) and Kleiber ratio at weaning (KR). The model included the fixed effects of sex of kid, type of birth, age of dam, year of birth, month of birth, and age of kid (days) as covariate that had significant effects, and random effects direct additive genetic, maternal additive genetic, maternal permanent environmental effects and residual. (Co) variance components were estimated using univariate and multivariate analysis by WOMBAT software applying four animal models including and ignoring maternal effects. Likelihood ratio test used to determine the most appropriate models. Heritability (h(a)(2)) estimates for BW, WW, ADG, and KR according to suitable model were 0.12 ± 0.05, 0.08 ± 0.06, 0.10 ± 0.06, and 0.06 ± 0.05, respectively. Estimates of the proportion of maternal permanent environmental effect to phenotypic variance (c(2)) were 0.17 ± 0.03, 0.07 ± 0.03, and 0.07 ± 0.03 for BW, WW, and ADG, respectively. Genetic correlations among traits were positive and ranged from 0.53 (BW-ADG) to 1.00 (WW-ADG, WW-KR, and ADG-KR). The maternal permanent environmental correlations between BW-WW, BW-ADG, and WW-ADG were 0.54, 0.48, and 0.99, respectively. Results indicated that maternal effects, especially maternal permanent environmental effects are an important source of variation in pre-weaning growth trait and ignoring those in the model redound incorrect genetic evaluation of kids.


The carboxyl-terminal fragment of osteopontin suppresses arginine-glycine-asparatic acid-dependent cell adhesion.
Osteopontin (OPN) is a secreted glycoprotein implicated in cell adhesion. It contains the arginine-glycine-asparatic acid (RGD) cell adhesive domain and the thrombin cleavage sequence. Although thrombin cleavage of OPN has been shown to be of physiological importance, the function of C-terminal OPN fragment cleaved by thrombin remains unknown. To determine its role, we performed cell adhesion assays using glutathione S-transferase-OPN fusion protein fragments and full-length OPN fusion protein. The N-terminal fragment containing RGD motif promoted enhanced adhesion of mouse and human fibroblasts by 2.9 and 2.8 folds in comparison with full-length OPN, respectively. The enhanced adhesion of both cells mediated by N-terminal fragment was significantly suppressed by addition of C-terminal fragment lacking RGD motif that has less cell adhesive property than full-length OPN. These results suggest that the C-terminal domain may play a pivotal role in regulating OPN functions by suppressing the RGD-dependent cell adhesion.


[Hernia repair at the groin - who undergoes which surgical intervention?].
Within the Guidelines of the European Hernia Society (EHS), there are disctinct statements about where and how inguinal hernia has to be surgically approached. In ASA-I and -II patients, it is recommended to perform the operation in an outpatient clinic setting. Male patients older than 30 years of age should undergo preferably surgical intervention using a mesh. In this context, there are two basic questions: "Are these recommendations already implemented in daily surgical practice (?)" and "Are these guidelines the road to success (?)", which are to be commented based on i) data from two registries, ii) data obtained in the surgical practice of the first author and iii) a selective literature search. An analysis was made of prospectively obtained data from two German registries (Herniamed registry [H-med]; Quality Assurance Inguinal Hernia Registry [QIHR]) and a consecutive and representative patient cohort of a single surgical practice [Surg-Pract] specialised in hernia surgery. Main results and concluding remarks are discussed in light of data reported in the literature. Proportions of hernia repair in an outpatient clinic setting were substantially different among the 3 groups (as follows): H-med (22.3 %), QIHR (62.7 %), Surg-Pract (80.5 %) whereas the percentages of ASA-I and -II patients differed only slightly: H-med (83.4 %), QIHR (89.5 %) and Surg-Pract (88.3 %). Recurrency rates after 12 months were 0.6 % (QIHR) and 0.7 % (Surg-Pract), respectively. In Surg-Pract, for 30 % of hernia repairs, "only" suturing for reconstruction was used. In ASA-I and -II patients, a substantial proportion of individuals can be surgically treated in an outpatient clinic setting with no disadvantages regarding high surgical quality and favourable outcome. Data from the national H-med indicated a much lower percentage of such patients than internationally reported and, in addition, a disproportionately high rate of endoscopic procedures. Moreover, reimbursement for hernia repair in an outpatient clinic setting is much worse in Germany compared with international standards, and, interestingly, there is by a factor of 1/3 an above average number of hospital beds in Germany compared with the OECD countries.


Endothelial function in children and adolescents with mucopolysaccharidosis.
Although coronary artery pathology is a prominent feature of mucopolysaccharidosis (MPS), it may be underestimated by coronary angiography because of its diffuse nature. It is also generally assumed that cardiovascular risk is increased in MPS and reduced following hematopoietic stem cell transplantation (HSCT) or enzyme replacement therapy (ERT), but this has never been formally evaluated. Non-invasive methods of assessing vascular endothelial function may provide a measure of cardiovascular risk in MPS. We evaluated endothelial function, using digital reactive hyperemia, in youth with MPS and in healthy controls. Digital reactive hyperemic index (RHI) was measured in 12 children and adolescents (age 10.3 ± 3.9 years old; 11 boys) with treated MPS and nine age- and gender-matched (11.4 ± 4.0; 8 boys) healthy controls. An independent t-test was used to compare RHI between individuals with MPS and controls. Children and adolescents with MPS (MPS type II: N = 5; type I: N = 4; type VI: N = 3) whether treated by HSCT (N = 4) or ERT (N = 8) had significantly lower RHI compared to controls (MPS 1.22 ± 0.19 vs. controls 1.46 ± 0.32, p < 0.05). These preliminary findings suggest that children and adolescents with treated MPS have significantly poorer endothelial function when compared to healthy controls. Further investigation into the utility of endothelial function for risk stratification and the long term implications of reduced endothelial function in MPS is warranted.


Anatomy and CT reconstruction of the anterior area of sphenoid sinus.
The anatomical structures of anterior area of sphenoid sinus are observed by CT reconstruction of radiographic images in some studies. However, the detailed anatomic information of the extended transsphenoidal approach is still incomplete. Fifteen cases (30 sides) of adult cadaveric skulls and 20 cases (40 sides) of bleached adult dry skulls were observed and measured under microscope. CT imaging data were obtained from 12 patients. Anatomy of anterior area of sphenoid sinus and sphenopalatine artery observed from CT three-dimensional reconstructed images was consistent with that observed from adult cadaveric skulls and bleached adult dry skulls. The anterior sphenoid sinus wall resembled a bird head, with midline protrude prismatically. The sphenoid ostia on both sides were in shape of bird-eyes, and the sphenoidal rostrum below was like the beak. The "shallowest point" was firstly reported in this study and was defined as the nearest point from the nostril to the anterior sphenoid sinus wall. It was located about 5.5 mm from sphenoid sinus ostium, and 5 mm from the upper edge of the posterior choanae. It was an important anatomical reference mark in locating the sphenoid sinus ostium in the anterior sinus wall. The three-dimensional images reconstructed by CT scan can visually display the bone structure of anterior area of sphenoid sinus, sphenopalatine artery and its main branches. Virtual endoscopy reconstruction can confirm the structural details of CT reconstruction and simulate transsphenoidal surgery.


Study on a new surfactant for removal of phenol from wastewater by emulsion liquid membrane.
Removal of phenol from wastewater using emulsion liquid membrane (ELM) is studied in present study. A new polyamine-type surfactant was synthesized and used for stabilizing of the emulsion phase. The results for the emulsion made by the synthesized surfactant showed much better stability and performance in the separation process compared to that by conventionally used Span 80. To determine the optimum operation conditions, the effect of several parameters such as emulsifier concentration, concentration of NaOH in the internal phase, oil to internal phase volume ratio, mixing intensity, temperature, solvent type, and stabilizer concentration have been investigated. It was found that under the optimum conditions, more than 98% of phenol can be removed in a single-stage process. The removal efficiency can be increased to 99.8% in a two-stage process.


The use of Seamguard to buttress the suture repair of a staple line leak following laparoscopic gastric bypass for obesity.
Anastomotic and staple line leak following laparoscopic gastric bypass are recognised complications with significant mortality and morbidity. Several techniques have been described to reduce the incidence of staple line leaks, including reinforcement of staple lines using omental wraps, fibrin glue, and Peristrips and Seamguard. Using a similar principle, we describe a case report of the successful use of a Seamguard buttress in the repair of a staple line leak at the proximal gastric pouch following laparoscopic gastric bypass. The repair of the leak was confirmed by gastrogaffin contrast study as well as clinically as the patient progressed well in the postoperative period. Ten months following surgery, her weight had reduced from 125 kg (BMI 47.6 kg/m(2)) to 82.4 kg (BMI of 31.4 kg/m(2)). We suggest that surgeons facing similar problems may choose to employ this novel technique.


Variables associated with adequate INR reversal in warfarin treated patients receiving 4-factor prothrombin complex concentrate.
Dosing of 4-factor prothrombin complex concentrate (4FPCC) in warfarin treated patients generally utilizes international normalized ratio (INR) and patient weight. The recommended maximum dosing for all INR categories is capped at 100 kg weight. Whether this affects INR reversal is unknown. Furthermore, characteristics associated with adequate INR reversal need to be further elucidated. This was a multi-center, retrospective cohort study of 186 patients who received 4FPCC for INR reversal in the setting of warfarin-associated hemorrhage or need for emergent INR reversal. Utilizing multiple regression analysis, we evaluated INR reversal, achievement of hemostasis, and 28-day all-cause mortality. A target INR < 1.4 was achieved in 132 of 186 patients (71%). Factors significantly affecting the odds of achieving target INR were age in years (OR 1.03; 95% CI 1.01-1.06; P = 0.01), weight-based 4FPCC dose (units/kg) (OR 1.04; 95% CI 1.00-1.08; P = 0.03), and 4FPCC dosing normalized to INR (units/kg/INR) (OR 1.18; 95% CI 1.03-1.35; P = 0.02). Hemostasis was achieved in 109 of 148 bleeding patients (73.6%). Blood transfusions were associated with not achieving hemostasis (OR 0.44; 95% CI 0.21-0.93; P = 0.03). All-cause 28-day mortality was 21.5% and was associated with intracranial hemorrhage (OR 2.83; 95% CI 1.38-5.8; P = 0.01). Adequate INR reversal was associated with age, weight-based 4FPCC dose, and dosing normalized to INR (units/kg/INR). Future studies should evaluate the appropriateness of current INR targets for warfarin reversal and alternative 4FPCC dosing strategies such as utilizing a 4FPCC dosing ratio of units/kg/INR.


Induction of micronuclei in mouse and hamster bone-marrow by chemical carcinogens.
Four carcinogens, dimethylnitrosamine (DMN), acetylaminofluorene (AAF), aflatoxin B1 (AFB1), and 3-methylcholanthrene (3-MC) were tested acutely and chronically in the micronucleus test in both mice and hamsters. In acute studies using mice, all compounds increased the relative frequency of micronuclei when compared to controls. There was a dose response which tended to tail off as bone-marrow suppression was observed. The order of activity appears to be DMN greater than AFB1 greater than or equal to 3-MC greater than AAF. In acute hamster studies, AFB1 was inactive at the highest dose tested (3 mg/kg). In the case of hamsters, all other compounds increased the incidence of micronuclei with DMN greater than 3-MC greater than AAF. Subacute studies with hamsters revealed that 3-MC was active at 1 week but not 8 weeks while DMN was active at both 1 and 8 weeks. AAF was active at 8 and 12 weeks and AFB1 was active at 12 weeks but not 8 weeks. The authors conclude that this test does not appear useful in chronic protocols and probably more reflects carcinogenicity of the test compounds than acute toxicity. Nevertheless, acute studies demonstrate that this test procedure is of value in the characterization of a compound's relative mutagenic potential.


Egr-1 increases in the prefrontal cortex following training in the context preexposure facilitation effect (CPFE) paradigm.
The context pre-exposure facilitation effect (CPFE) is a modified form of standard contextual fear conditioning that dissociates learning about the context during a preexposure phase from learning the context-shock association during an immediate shock training phase conducted on separate days. Fear conditioning in the CPFE is an associative process in which only animals that are preexposed to the same context they are later given an immediate shock in demonstrate freezing when tested for conditioned fear memory. Previous research has shown that the hippocampus and amygdala are necessary for different phases of the CPFE, but whether other brain regions are also involved is unknown. The present study examined expression of the immediate-early gene early growth response gene 1 (Egr-1; also called Zif268, Ngfi-a, Krox-24) in the dorsal hippocampus, lateral nucleus of the amygdala, retrosplenial cortex, and several prefrontal cortex regions (infralimbic and prelimbic medial prefrontal cortex, anterior cingulate, and orbitofrontal cortex) following each phase of the CPFE in juvenile rats. Animals preexposed to the conditioning context displayed fear conditioned freezing during a retention test whereas rats preexposed to an alternate context did not. Following context preexposure, Egr-1 mRNA was elevated in context and alternate context exposed animals compared to home-cage control rats in almost all regions analyzed. Following the context-shock training phase, fear conditioned rats displayed significantly more Egr-1 mRNA expression in the infralimbic, prelimbic, and orbitofrontal cortices compared to the alternate context preexposed control rats. These differences in Egr-1 expression were not found in amygdala between the preexposed context and alternate context rats. No sex differences were observed following preexposure or training in any regions analyzed. The findings suggest that increased expression of Egr-1 within the prefrontal cortex is associated with contextual fear conditioning in the CPFE paradigm.


Minimal debridement or simple wound closure as the only surgical treatment in war victims with low-velocity penetrating head injuries. Indications and management protocol based upon more than 8 years follow-up of 99 cases from Iran-Iraq conflict.
During military conflicts, surviving victims traditionally underwent large enough craniectomy or craniotomy to achieve extensive debridement of the in-driven bone, shell fragments, and debris. Meanwhile, the completely as well as the partially devitalized adjacent brain tissue would also be debrided. This might have led to additional neurologic deficit or lesser degree of recovery of functions. We studied the efficacy and safety of much more limited or even absence of surgical intervention in a selected group of wartime head-wounded patients. Among 1,150 war victims with penetrating head wounds referred to two major centers affiliated with Tehran University of Medical Sciences during the 8-year period spanning the Iran-Iraq conflict, there were 191 head-wounded patients who underwent either no surgical intervention or a very limited debridement. We have attempted to follow up as closely as possible for more than 8 years. Ninety-nine of them fulfilled the criteria to be included in this series. Close follow-up for development of cerebral infections, functional recovery, or development of new neurologic deficits and epilepsy were performed. At least 3 contrast-enhanced CT scans were taken for each patient. All patients were victims of the battle-field areas with low- to moderate-velocity missile or shell fragment injury. The Glasgow Coma Scale (GCS) scores of the patients were between 8-14 when visited by the first attending neurosurgery staff. The factors considered to be effective in the outcome analysis were the entry point, the number of the in-driven bone fragments, the retained shell fragments, the brain compartments affected, and the paranasal sinus or skull base involvement with or without cerebrospinal fluid (CSF) fistula. There were 13 unilobar, 44 bilobar, 4 trilobar, 38 transventricular, and 3 skull base lesions. The number of retained metal fragments varied between 1 to 6. The number of retained bone fragments varied between 1 to 5 in 73 victims and more than five chips in other cases. The outcome was good (back to work) in 90 patients and poor (severely disabled) in 4. Five patients died because of severity of brain damage and meningitis. The effect of the different enumerated variables upon the outcome was measured using chi(2) and Fisher exact test, which was nonsignificant for all of the variables except for the orbitofacial entry point of injury (p = 0.00006). This study seems to indicate that not only is reoperation for retained bone or shell fragments unnecessary, but surgeons having modern neuroradiological instruments available to detect the proper explanation for changes in GCS of the patients may decide not to proceed with any surgical intervention in a good number of patients. As a result of the "no surgical treatment protocol," one can preserve cerebral tissue without exposing the patient to undue risk of seizures, infection, or death by leaving behind some or all the in-driven bone and shell fragments.


Complete versus incomplete cytoreduction in peritoneal carcinosis from gastric cancer, with consideration to PCI cut-off. Systematic review and meta-analysis.
The completeness of cytoreduction has been considerated as fundamental in increasing the life expectancy in patients with peritoneal carcinosis (PC) in gastric cancer. However no definitive data about the real effect of complete cytoreduction (CC) have still been published. Moreover the PCI cut-off to attempt CC with a reasonable risk-benefit ratio still lacks. A systematic review with meta-analysis of trials of complete vs incomplete cytoreduction in patients with peritoneal carcinosis from GC was performed. Nine trials have been included (748 patients: 417 with CC0-CC1 and 324 with CC2-CC3 cytoreduction). 1, 2, 3 and 5 years survival is favorable to CC0-CC1 (Risk Ratio: 2.41, 8.18, 8.66, and 7.96 respectively). CC0 vs. CC1 survival benefit at 1 and 3 years: RR 2.28 and 6.36 respectively, favoring CC0. 1, 2, 3 and 5 years survival changes significantly above and below a PCI of 12. 1, 2, 3 and 5-year overall survival is increased by CC0-CC1 cytoreduction in patients with PC from gastric origin. Moreover CC0 increases the 1 and 3 years survival when compared to CC1 cytoreduction.


Epigenetic regulation is involved in traffic-related PM2.5 aggravating allergic airway inflammation in rats.
Increasing fine particulate matter (PM2.5) and epigenetic modifications are closely associated with the pathogenesis of asthma, but the definite mechanism remains unclear. The traffic-related PM2.5 exposure aggravated pulmonary inflammation and changed the methylation level of interferon gamma (Ifng) and interleukin (Il)4 genes, and then altered levels of affiliated cytokines of IFN-γ and IL-4 in rats with allergic airway inflammation. It also increased the level of miR146a and decreased the level of miR31. In addition, transcription factors of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 6 (Stat6) rose; forkhead box P3 (Foxp3) and signal transducer and activator of transcription 4 (Stat4) lowered. The traffic-related PM2.5 altered epigenetic modifications in allergic airway inflammation of rats leading to inflammation exacerbation through impaired regulatory T (Treg) cells function and T-helper type 1 (Th1)/Th2 cells imbalance, which provided a new target for the treatment and control of asthma.


Xanthine Oxidase Activation Modulates the Endothelial (Vascular) Dysfunction Related to HgCl2 Exposure Plus Myocardial Infarction in Rats.
Heavy metal exposure is associated with cardiovascular diseases such as myocardial infarction (MI). Vascular dysfunction is related to both the causes and the consequences of MI. We investigated whether chronic exposure to low doses of mercury chloride (HgCl2) worsens MI-induced endothelial dysfunction 7 days after MI. Male Wistar rats were divided into four groups: Control (vehicle), HgCl2 (4 weeks of exposure), surgically induced MI and combined HgCl2-MI. Morphological and hemodynamic measurements were used to characterize the MI model 7 days after the insult. Vascular reactivity was evaluated in aortic rings. Chronic HgCl2 exposure did not cause more heart injury than MI alone in terms of the morphological or hemodynamic parameters. Vascular reactivity increased in all groups, but the combination of HgCl2-MI increased the vasorelaxation induced by ACh compared with the HgCl2 and MI groups. Results showed reduced endothelial nitric oxide synthase (eNOS) protein expression in the MI group; increased iNOS activity in the HgCl2-MI group, although without enough magnitude to reverse the reduction in NO bioavailability; and increased phenylephrine response in the HgCl2-MI group due to an increase in ROS production, notably via xanthine oxidase (XO). Results suggest that the combination of 1 month pre-exposure of HgCl2 before MI changed the endothelial generation of oxidative stress induced by mercury exposure from NADPH oxidase pathway to XO (xanthine oxidase)-dependent ROS production.


Sirtuin 4 Regulates Lipopolysaccharide Mediated Leydig Cell Dysfunction.
Bacterial lipopolysaccharide (LPS) is the most important contributing factor in pathogenesis of bacterial infection in male accessory glands; and it has shown to inhibit testicular steroidogenesis and induce apoptosis. The present study demonstrates that LPS causes mitochondrial dysfunction via suppression of sirtuin 4 (SIRT4); which in turn affects Leydig cell function by modulating steroidogenesis and apoptosis. LC-540 Leydig cells treated with LPS (10 µg/ml) showed impaired steroidogenesis and increased cellular apoptosis. The mRNA and protein expression of SIRT4 were decreased in LPS treated cells when compared to controls. The obtained data suggest that the c-Jun N-terminal kinase (JNK) activation suppresses SIRT4 expression in LPS treated Leydig cells. Furthermore, the overexpression of SIRT4 prevented LPS induced impaired steroidogenesis and cellular apoptosis by improving mitochondrial function. These findings provide valuable information that SIRT4 regulates LPS mediated Leydig cell dysfunction.


Breast cancer survivors' perception of survivorship.
To explore (a) how women who were diagnosed with breast cancer (BC) defined themselves as survivors and when this occurred, and (b) the types of benefits they derived from their experiences. An exploratory, qualitative approach. 112 women who had BC (response rate = 70%). Participants were recruited from two cancer survivor organizations in a northeastern U.S. city. Responses to open-ended questions in telephone interviews were examined by age at diagnosis using thematic analysis. Chi squares were used to conduct analyses by age (younger than 51 years; aged 51 years or older). Meaning of survivorship, defining moment, benefits derived from surviving from breast cancer. Participants' perceptions of survivorship included two main components, a defining moment and the meaning attached to being a survivor. Becoming a survivor is an active process, except in the case of those participants who realized they were survivors when informed by a third party. Meanings differed by age at diagnosis. Most participants listed at least one benefit from surviving cancer. The definitions of survivorship and benefits outlined here suggest that many positive aspects of the survivorship experience exist that may inform future interventions' designs. Providers should acknowledge the strength survivors show in the process of meaning-making and finding benefits in their adverse experiences. The use of expressive and supportive interventions may hold promise for women facing difficulties in coping with their diagnosis.


Designing receptor agonists with enhanced pharmacokinetics by grafting macrocyclic peptides into fragment crystallizable regions.
Short half-lives in circulation and poor transport across the blood-brain barrier limit the utility of cytokines and growth factors acting as receptor agonists. Here we show that surrogate receptor agonists with longer half-lives in circulation and enhanced transport rates across the blood-brain barrier can be generated by genetically inserting macrocyclic peptide pharmacophores into the structural loops of the fragment crystallizable (Fc) region of a human immunoglobulin. We used such 'lasso-grafting' approach, which preserves the expression levels of the Fc region and its affinity for the neonatal Fc receptor, to generate Fc-based protein scaffolds with macrocyclic peptides binding to the receptor tyrosine protein kinase Met. The Met agonists dimerized Met, inducing biological responses that were similar to those induced by its natural ligand. Moreover, lasso-grafting of the Fc region of the mouse anti-transferrin-receptor antibody with Met-binding macrocyclic peptides enhanced the accumulation of the resulting Met agonists in brain parenchyma in mice. Lasso-grafting may allow for designer protein therapeutics with enhanced stability and pharmacokinetics.


Interface problems: structural constraints on interpretation?
Five experiments investigated the interpretation of quantified noun phrases in relation to discourse structure. They demonstrated, using questionnaire and on-line reading techniques, that readers in English prefer to give a quantified noun phrase in (VP-external) subject position a presuppositional interpretation, in which the noun phrase limits or restricts the interpretation of an already available set, rather than giving it a nonpresuppositional or existential interpretation, in which it introduces completely new entities into the discourse. Experiment 1 showed that readers prefer a presuppositional interpretation of three ships over the existential interpretation in Five ships appeared on the horizon. Three ships sank. Experiment 2 showed longer reading times in sentences that are disambiguated toward the existential interpretation than in sentences that permit the presuppositional interpretation. Experiment 3 suggested that the presuppositional preference is greater when the phrase three ships occurs outside the verb phrase than when it occurs inside the verb phrase. Experiment 4 showed that Korean subjects marked with a topic marker received more presuppositional interpretations than subjects marked with a nominative marker. Experiment 5 showed that German subjects in VP-external (but nontopic) position received more presuppositional interpretations than VP-internal subjects. The results suggest the syntactic position of a phrase is one determinant of its interpretation, as expected according to the mapping hypothesis of Diesing (1992).


Evaluation of intestinal absorption of amtolmetin guacyl in rats: breast cancer resistant protein as a primary barrier of oral bioavailability.
The purpose of the present study was to investigate the role of efflux transporters on the intestinal absorption of amtolmetin guacyl (MED-15). The effects of P-glycoprotein (P-gp), multiple resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on intestinal absorption amount of MED-5 (tolmetin-glycine amide derivative), the metabolite formed from MED-15 in the intestinal epithelial cells were studied in the in vitro everted gut sac experiments. Moreover, the in situ single-pass intestine perfusion was adopted to clarify the role of efflux transporters in excreting MED-5 in knockout mice. The plasma concentration of MED-5 and tolmetin, the metabolite formed from MED-5 was determined in Bcrp1 knockout mice and wild-type mice. BCRP inhibitor Ko143 (50 μM and 100 μM) significantly increased the intestinal absorption amount in jejunum, ileum and colon (p<0.05). However, no effect was observed in the presence of P-gp inhibitor verapamil and MRP2 inhibitor MK571 in each intestinal segment. Furthermore, the plasma concentration MED-5 and tolmetin, metabolites of MED-15, increased 2-fold and 4-fold, respectively, in Bcrp1 knockout mice compared with wild-type mice after the single-pass perfusion of small intestine with MED-15. It may be concluded that BCRP plays an important role in the intestinal efflux of MED-5 and limits the bioavailability after oral administration of MED-15.


Partial pericardial defect associated with ruptured aortic dissection of the ascending aorta: a rare feature presenting severe left hemothorax without cardiac tamponade.
We report a very rare case of acute aortic dissection of the ascending aorta, which ruptured to the left pleural cavity through the left-side congenital pericardial defect. A preoperative computed tomographic scan and a roentgenogram showed localized dissection of the ascending aorta and severely deteriorating left hemothorax, which required emergency operation. Intraoperative findings revealed the ruptured aortic dissection of the ascending aorta and the defect at the left-side pericardium, and a graft replacement of the ascending aorta was performed. It was considered that congenital pericardial defect complicates the diagnosis in a case of catastrophic intrapericardial hemorrhage.


A case of fluoxetine-induced syndrome of inappropriate antidiuretic hormone secretion.
A 58-year-old schizophrenic male who had been drinking at least 4-5 l of pure water every day for 30 years was admitted to a hospital with complaints of nausea, fatigue, and irregular, fluctuating fevers (up to 39 degrees C). He had previously been prescribed fluoxetine at a dose of 20 mg/day and had been using the drug for 28 days. Review of medical history, physical examination, blood analysis, urine analysis, chest radiography and abdominal ultrasound. Psychogenic polydipsia and fluoxetine-induced syndrome of inappropriate antidiuretic hormone secretion. Fluid restriction and discontinuation of fluoxetine.


T-L technique for HoLEP: perioperative outcomes of a large single-centre series.
The aim of this article was to describe, step-by-step, an original technique (T-L technique) in a single centre series of patients who underwent holmium laser enucleation of the prostate (HoLEP) for symptomatic benign prostatic hyperplasia and analyze perioperative outcomes. We retrospectively analyzed data of 567 patients who underwent HoLEP. The T-L technique consists of a series of incisions used as landmarks, performed at the beginning of the procedure before enucleation. Two T-shape incisions are performed at the level of bladder neck (at the 5-7 and 12 o'clock positions); two L-shape incisions are performed at the level of verumontanum, bilaterally, to mark the apex and to limit the sphincter. Another T-shape incision is performed on the bladder neck at the 12 o'clock position posterior to the level of verumontanum. The median operative time (OT) was 80 minutes (IQR 64-105); 50 minutes (IQR 35-70) and 15 minutes (IQR 10-20) for enucleation and the morcellation phase, respectively. Conversion to transurethral resection of the prostate (TURP) was necessary in 3/567 (0.6%) patients. Intraoperative complications occurred in 3.4% of cases, capsule perforation occurred in 12/567 (2%) of cases, while bladder perforation during morcellation occurred in 8/567 (1.4%) of cases. Postoperative complications were observed in 20/567 (3.5%) of patients. Specifically, grade 1-2 occurred in 19/567 (3.3%) and grade 3 was recorded in 1/567 (0.2%). The T-L technique for HoLEP is safe and reproducible with a low rate of perioperative complications. The positioning of some landmarks before enucleation allows for the better orientation during enucleation and could be very useful in case of large prostates.


Thrombocytopenia in the critically ill: prevalence, incidence, risk factors, and clinical outcomes.
The aim of this cohort study was to describe the prevalence, incidence, and risk factors for thrombocytopenia in the intensive care unit (ICU) and to evaluate the impact of thrombocytopenia on mortality with further comparisons amongst major diagnostic categories. Patients admitted to the ICU from 1997-2011 for cardiac, medical, surgical, and trauma conditions were included. The presence of a platelet count < 100 × 10(9)·L(-1) on admission day or its appearance during ICU stay were considered as prevalent and incident thrombocytopenia, respectively. Risk factors for thrombocytopenia and the influence of thrombocytopenia on mortality were also analyzed. This study included 20,696 patients. Prevalent and incident thrombocytopenia occurred in 13.3% and 7.8% of patients, respectively, with associated mortality rates of 14.3% and 24.7%, respectively, compared with 10.2% in the group with normal platelet count (P < 0.001). After adjustments, thrombocytopenia remained associated with an increased risk of mortality (odds ratio 1.25; 95% confidence interval 1.20 to 1.31; P < 0.001). The greatest impact of thrombocytopenia on mortality was observed in the cancer, respiratory, digestive, genitourinary, and infectious diagnostic categories. Independent risk factors included age, female sex, admission platelet counts and hemoglobin, mechanical ventilation, days of hospitalization prior to ICU admission, liver cirrhosis, hypersplenism, coronary bypass grafting, intra-aortic balloon pump placement, acute hepatitis, septic shock, and pulmonary embolism or deep vein thrombosis. Thrombocytopenia in the ICU is associated with an independent risk of mortality that varies greatly depending on diagnostic admission category.


Types of repairs used by normally developing and language-impaired preschool children in response to clarification requests.
Competent communicators learn to regulate and modify speech within a conversational dyad. Speech modifications may entail selecting appropriate words, reducing the complexity of utterances, or elaborating for clarification [Leonard Top. Lang. Disord. 4:28-37 (1983)]. This study was designed to examine how 4- to 5 1/2-year-old language-impaired children respond to clarification requests; how their repairs differ from two groups of matched controls; and how type of request affects the repair. Fifteen boys served as subjects, five with language impairments and 10 controls with normal language, half matched for age and cognition and half matched for verbal competence. Three types of requests were used: requests for confirmation, neutral requests, and requests for specific constituent repetition. All three groups of children in this study overwhelmingly used revisions to repair their original utterances. The repair strategies used by the language-impaired children did not differ from the controls. The clinical implications of the findings are discussed.


Surface-modified nanoerythrosomes for potential optical imaging diagnostics.
Nanoerythrosomes (NERs), vesicle-like nanoparticles derived from red blood cells, represent a new and interesting vector for therapeutic molecules and imaging probes, mainly thanks to their high stability and excellent biocompatibility. Aiming to present a proof-of-concept of the use of NERs as diagnostic tools for in vitro/in vivo imaging purposes, we report here several functionalization routes to decorate the surfaces of NERs derived from bovine blood with two different fluorophores: 7-amino-4-methylcumarin and dibenzocyclooctinecyanine5.5. Notably, the fluorophores were cross-linked to the NERs surface with glutaraldehyde and, in the case of dibenzocyclooctinecyanine5.5, also using a click-chemistry route, termed strain-promoted azide-alkyne cycloaddition. The physicochemical characterization highlighted the high stability of the NERs derivatives in physiological conditions. Furthermore, the loading efficiency of the fluorophores on the NERs surface was evaluated using both UV-Vis spectroscopy and fluorescence microscopy.


Prognostic and clinicopathological value of MUC1 expression in colorectal cancer: A meta-analysis.
Accumulating evidence supports the overexpression of mucin 1 (MUC1) in colorectal cancer (CRC), but the value of elevated MUC1 expression remains controversial. Here, we evaluated the prognostic and clinicopathological value of MUC1 expression in CRC. The Web of Science, PubMed, Embase, Cochrane Library, and Wanfang databases, as well as the China Biology Medicine disc (CBMdisc) and China National Knowledge Infrastructure (CNKI) were searched for studies on MUC1 expression and prognosis of CRC through July 20, 2018. The pooled relative risks (RRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated to evaluate the prognostic and clinicopathological value of MUC1 expression in CRC. The Revman version 5.3 package and STATA, version 12 were employed for pooled analysis and analysis of publication bias. This meta-analysis included 16 published studies. The combined analysis showed that CRC patients with high MUC1 expression had a worse clinical outcome in overall survival (OS) (HR = 1.51, 95% CI = 1.30-1.75, P <.00001). In addition, high MUC1 expression was associated with higher TNM stage (RR = 1.44, 95% CI = 1.17-1.77, P = .0007), greater depth of invasion (RR = 1.30, 95% CI = 1.10-1.53, P = .002), and lymph node metastasis (RR = 1.47, 95% CI = 1.20-1.80, P = .0002) of CRC. However, the elevated MUC1 expression was not related to disease-free survival/recurrence-free survival (DFS/RFS) (HR = 1.51, 95% CI = 0.78-2.89, P = .22), histological grade (RR = 1.15, 95% CI = 0.96-1.38, P = .12), gender (RR = 0.95; 95% CI = 0.83-1.08, P = .44), tumor size (RR = 1.11, 95% CI = 0.85-1.44, P = .44), tumor site (RR = 1.01, 95% CI = 0.88-1.16, P = .84), or mucinous component (RR = 0.83, 95% CI = 0.60-1.14, P = .24) in CRC. Our findings indicated that high MUC1 expression represents a marker of poor prognosis in CRC. Meanwhile, elevated MUC1 expression was associated with advanced TNM stage, greater depth of invasion, and lymph node metastasis.


Chronic inflammatory demyelinating polyneuropathy.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized clinically by a progressive symmetrical weakness evolving over a period of at least 2 months. There is increased CSF protein and conduction block, reduced nerve conduction velocities, increased distal latencies, and/or absent F wave or prolonged F wave latency in two or more nerves. Incidence is lower in children (10 times less) than in adults, and the condition presents in an acute or subacute manner with frequent relapses. It is not associated with other systemic diseases such as neoplasia, diabetes mellitus, or monoclonal gammopathies. It appears to be immune-related as a variety of humoral and cellular autoimmune mechanisms have been implicated. Treatment is based on results obtained in randomized clinical trials (RCTs) conducted in adults as such studies are lacking in the pediatric population. The evolution of CIDP is more favorable in children than in adults, with 80-100% response rates to standard treatments (steroids, intravenous immunoglobulins, and/or plasmapheresis) and excellent outcome with complete functional recovery in most patients. Cases refractory to standard therapies do exist in children, for which azathioprine, methotrexate, and mycophenolate mofetil alone or more often in association with other treatments have been used. However, safety and efficacy data are still insufficient to give specific recommendations regarding the optimal choice.


Psychosocial factors associated with broadly defined bulimia nervosa during early pregnancy: findings from the Norwegian Mother and Child Cohort Study.
The purpose of the present study was to investigate the relationship between psychosocial characteristics and broadly defined bulimia nervosa during early pregnancy, including factors associated with continuation, incidence and remission. A total of 41 157 women completed questionnaires at approximately gestation week 18, including items on eating disorders and psychosocial characteristics as a part of Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Incident bulimia nervosa during the first trimester was significantly associated with symptoms of anxiety and depression and low self-esteem and life satisfaction, whereas remission was significantly associated with higher self-esteem and life satisfaction. Continuation was not significantly related to any of the psychosocial variables tested. Onset of bulimia nervosa during pregnancy is associated with mood and anxiety symptoms. Remission of bulimic symptoms and new onset of bulimia nervosa are associated with opposite profiles of self-esteem, and life satisfaction measures.


Selective suppression of IL-10 transcription by calcineurin in dendritic cells through inactivation of CREB.
Myeloid cells play a pivotal role in immune responses against bacterial and fungal infection. Among innate immune receptors, C-type lectin receptors (CLRs) can induce a wide spectrum of cytokines through immunoreceptor tyrosine-based activation motifs (ITAMs)-mediated signaling pathways. Dendritic cells (DCs) produce IL-10 through CLR stimulation; however, the regulatory mechanism of IL-10 expression has not been elucidated. In the current study, we report that calcium (Ca2+) signaling-deficient DCs produced more IL-10 than wild-type DCs. Mechanistically, Ca2+-dependent phosphatase calcineurin directly inactivates cAMP response element-binding protein (CREB), a transcription factor of Il10 in DCs, through dephosphorylating CREB at serine 133. In calcineurin-deficient DCs, CREB was highly phosphorylated and increased its binding to the Il10 promoter. Elimination of mitogen-activated protein kinase (MAPK) signaling that phosphorylates CREB, deficiency of CREB, as well as deletion of a CREB-binding site in the Il10 promoter could diminish IL-10 production in DCs. Our findings identified a novel substrate of calcineurin as well as a mechanism through which Ca2+ signaling regulates IL-10 expression downstream of CLRs. As IL-10 is a crucial immunosuppressive cytokine, this mechanism may counteract the over-activated IL-10-producing signals induced by CARD9 and MAPK pathways, preventing the ineffectiveness of the immune system during bacterial and fungal infection.


A study of the fine structure of the pit organ of the common Japanese sea eel Conger myriaster.
The fine structure of the pit organ of the sea eel has been studied by means of electron microscopy. The sensory epithelium of the pit organ consists of sensory cells and supporting cells. The apical surface of the sensory cell is studded with sensory hairs consisting of a kinocilium and stereocilia. The sensory cells are divided into two groups. In one, the kinocilium points dorsally and in the other the kinocilium points ventrally. The total number of sensory cells in one pit organ is about 100, and the ratio of cells with opposite polarity is about 1:1. On the basis of these structural features, the pit organ is considered to be a mechano-receptor sensitive to the movement of liquid in a dorso-ventral direction. It may also serve as an ion receptor, sensitive to environmental ion concentration. Efferent nerve terminals make rare synaptic contacts on the afferent nerve fiber.


Photoactivated Fluorescence Enhancement in F,N-Doped Carbon Dots with Piezochromic Behavior.
Photoactivation in CdSe/ZnS quantum dots (QDs) on UV/Vis light exposure improves photoluminescence (PL) and photostability. However, it was not observed in fluorescent carbon quantum dots (CDs). Now, photoactivated fluorescence enhancement in fluorine and nitrogen co-doped carbon dots (F,N-doped CDs) is presented. At 1.0 atm, the fluorescence intensity of F,N-doped CDs increases with UV light irradiation (5 s-30 min), accompanied with a blue-shift of the fluorescence emission from 586 nm to 550 nm. F,N-doped CDs exhibit photoactivated fluorescence enhancement when exposed to UV under high pressure (0.1 GPa). F,N-doped CDs show reversible piezochromic behavior while applying increasing pressure (1.0 atm to 9.98 GPa), showing a pressure-triggered aggregation-induced emission in the range 1.0 atm-0.65 GPa. The photoactivated CDs with piezochromic fluorescence enhancement broadens the versatility of CDs from ambient to high-pressure conditions and enhances their anti-photobleaching.


Implementation of national diabetes retinal screening programme is associated with a lower proportion of patients referred to ophthalmology.
To examine the impact of a new national retinal screening programme on screening attendance, technical quality of images, and referrals to the ophthalmology clinic. Results from the previous ad hoc retinal screening service were compared with data from the first year of the new Scottish Diabetes Retinal Screening Programme in Dundee, which was administered according to criteria recommended by the Health Technology Board Scotland. Of 5150 patients invited for screening, 10.3% of patients did not attend. Overall, 4574 patients underwent single-field digital retinal photography and 25.4% required mydriasis for an adequate image. After screening, 1.9 and 90.5% were recalled for repeat photography at 6 months and 1 year, respectively, whilst 4.6% were ungradable and 3.0% were referred to the ophthalmology clinic. Compared with the last 18 months of the previous scheme, with the new programme a smaller proportion of patients were referred to ophthalmology (3.0 vs. 5.9%; P < 0.001, difference 2.9%: 95% confidence interval 2.1-3.7%). Moreover, the attendance was higher (89 vs. 82%; P < 0.01) and there were fewer ungradable images (4.6 vs. 7.1%; P < 0.001). Introduction of a systematic retinal screening programme can reduce the proportion of patients referred to the ophthalmology clinic, and use ophthalmology services more efficiently.


Possibilities and Challenges of Delivering Health-Related Small Group Interventions Online: Scoping Review.
The outbreak of the COVID-19 pandemic required the transition of health-related face-to-face group interventions to an online setting. While it seems that group outcomes can be realized in an online setting, less is known about resulting potential challenges (and advantages) and how these can be overcome. The aim of this article is to explore what challenges and advantages may arise when providing health-related small group interventions in an online setting and how to overcome these challenges. Scopus and Google Scholar databases were searched for relevant literature. Effect studies, meta-analyses, literature reviews, theoretical frameworks, and research reports relating to synchronous, face-to-face, health-related small group interventions, online group interventions, and video teleconferencing group interventions were identified and screened. Findings relating to potential challenges and corresponding strategies are described. In addition, potential advantages of online group settings were explored. Relevant insights were gathered until saturation of results relating to the research questions was reached. The literature indicated several aspects that require extra attention and preparation in the online group setting. These include the delivery of nonverbal communication and affect regulation, as well as the build-up of group cohesion and therapeutic alliance, which seem more challenging online. Yet there are strategies to overcome these challenges, such as metacommunication, collecting participant feedback, and providing guidance concerning technical accessibility. In addition, the online setting provides opportunities to reinforce group identity, such as by allowing independence and the ability to create homogeneous groups. While online, health-related small group interventions offer a considerable number of possibilities and benefits compared to face-to-face groups, there are also potential drawbacks to consider, which, if anticipated, can be to a great extent overcome.


Type IV Collagens and Basement Membrane Diseases: Cell Biology and Pathogenic Mechanisms.
Basement membranes are highly specialized extracellular matrices. Once considered inert scaffolds, basement membranes are now viewed as dynamic and versatile environments that modulate cellular behaviors to regulate tissue development, function, and repair. Increasing evidence suggests that, in addition to providing structural support to neighboring cells, basement membranes serve as reservoirs of growth factors that direct and fine-tune cellular functions. Type IV collagens are a major component of all basement membranes. They evolved along with the earliest multicellular organisms and have been integrated into diverse fundamental biological processes as time and evolution shaped the animal kingdom. The roles of basement membranes in humans are as complex and diverse as their distributions and molecular composition. As a result, basement membrane defects result in multisystem disorders with ambiguous and overlapping boundaries that likely reflect the simultaneous interplay and integration of multiple cellular pathways and processes. Consequently, there will be no single treatment for basement membrane disorders, and therapies are likely to be as varied as the phenotypes. Understanding tissue-specific pathology and the underlying molecular mechanism is the present challenge; personalized medicine will rely upon understanding how a given mutation impacts diverse cellular functions.


Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.
Morphiceptin (Tyr-Pro-Phe-Pro-NH2), a tetrapeptide amide, is a selective ligand of the μ-opioid receptor (MOR). This study reports the synthesis and biological evaluation of a series of novel morphiceptin analogs modified in positions 2 or/and 4 by introduction of 4,4-difluoroproline (F2Pro) in l or d configuration. Depending on the fluorinated amino acid configuration and its position in the sequence, new analogs behaved as selective full MOR agonists showing high, moderate, or relatively low potency. The most potent analog, Tyr-F2Pro-Phe-D-F2Pro-NH2, was also able to activate the κ-opioid receptor (KOR), although with low potency. Docking studies and the comparison of results with the high resolution crystallographic structure of a MOR-agonist complex revealed possible structure-activity relationships of this compound family.


Human Annulus Fibrosus Dynamic Tensile Modulus Increases with Degeneration.
The annulus fibrosus (AF) of the intervertebral disc experiences cyclic tensile loading in vivo at various states of mechanical equilibrium. Disc degeneration is associated with alterations in the biochemical composition of the AF including decreased water content, decreased proteoglycan concentration, and increased collagen deposition that affect mechanical function of the AF in compression and shear. Such changes may also affect the dynamic viscoelastic properties of the AF and thus alter the disc's ability to dissipate energy under physiologic loading. The objectives of this study were to quantify the dynamic viscoelastic properties of human AF in circumferential tension and to determine the effect of degeneration on these properties. Nondegenerated and degenerated human AF tensile samples were tested in uniaxial tension over a spectrum of loading frequencies spanning 0.01Hz to 2Hz at several states of equilibrium strain to determine the dynamic viscoelastic properties (dynamic modulus, phase angle) using a linear viscoelastic model. The AF dynamic modulus increased at higher equilibrium strain levels. The AF behaved more elastically at higher frequencies with a decreased phase angle. Degeneration resulted in a higher dynamic modulus at all strain levels but had no effect on phase angle. The findings from this study elucidate the effect of degeneration on the dynamic viscoelastic properties of human AF and lend insight into the mechanical role of the AF in cyclic loading conditions.


Outcomes After Shoulder Replacement Surgery in the Young Patient: How Do They Do and How Long Can We Expect Them to Last?
Glenohumeral arthritis in the young, active patient remains a challenging problem shoulder surgeons face. Anatomic total shoulder arthroplasty has been proven to be a successful operation for patients with end-stage shoulder arthritis; however, concerns over long-term implant survival remain. These concerns are amplified in young patients and largely revolve around the placement of a glenoid component, which is seen as the "weak link" in shoulder arthroplasty. Here we discuss the reported outcomes and survivorship of the different shoulder arthroplasty options in young patients.


A critical review on antibiotics and hormones in swine wastewater: Water pollution problems and control approaches.
Swine wastewater (SW) is an important source of antibiotics and hormones (A&H) in the environment due to their large-scale application in swine industry. A&H in SW can be released into the water environment through the direct discharge of SW, effluent from SW treatment plants, and runoff and leaching from farmland polluted by swine wastes. The presence of A&H in the water environment has become an increasing global concern considering their adverse effects to the aquatic organism and human. This review critically discusses: (i) the occurrence of A&H in global water environment and their potential risks to water organisms and human; (ii) the management and technical approaches for reducing the emission of A&H in SW to the water environment. The development of antibiotic alternatives and the enhanced implementation of vaccination and biosecurity are promising management approaches to cut down the consumption of antibiotics during swine production. Through the comparison of different biological treatment technologies for removing A&H in SW, membrane-based bioprocesses have relatively higher and more stable removal efficiencies. Whereas, the combined system of bioprocesses and AOPs is expected to be a promising technology for elimination and mineralization of A&H in swine wastewater. Further study on this system is therefore necessary.


T-cell dysregulation in COVID-19.
T-cells play key roles in immunity to COVID-19 as well as the development of severe disease. T-cell immunity to COVID-19 is mediated through differentiated CD4+ T-cells and cytotoxic CD8+ T-cells, although their differentiation is often atypical and ambiguous in COVID-19 and single cell dynamics of key genes need to be characterized. Notably, T-cells are dysregulated in severe COVID-19 patients, although their molecular features are still yet to be fully revealed. Importantly, it is not clear which T-cell activities are beneficial and protective and which ones can contribute to the development of severe COVID-19. In this article, we examine the latest evidence and discuss the key features of T-cell responses in COVID-19, showing how T-cells are dysregulated in severe COVID-19 patients. Particularly, we highlight the impairment of FOXP3 induction in CD4+ T-cells and how the impaired FOXP3 expression can lead to the differentiation of abnormally activated (hyperactivated) T-cells and the dysregulated T-cell responses in severe patients. Furthermore, we characterise the feature of hyperactivated T-cells, showing their potential contribution to T-cell dysregulation and immune-mediated tissue destruction (immunopathology) in COVID-19.


Saporin induces multiple death pathways in lymphoma cells with different intensity and timing as compared to ricin.
Ribosome-inactivating protein (RIP)-containing immunotoxins are currently used in clinical trials as anti-tumour drugs, in particular against haematological malignancies. In cell killing-based therapies it is important to identify the death pathways induced by the cytotoxic agent. The purpose of this work was to compare the pathways of cell death induced by the RIP saporin with those carried out by ricin in the L540 human Hodgkin's lymphoma-derived cell line. Protein synthesis inhibition, activation of caspases, DNA fragmentation and loss of viability have been evaluated. The two toxins triggered a similar DNA fragmentation and cell death, at concentrations giving the same level of cell protein synthesis inhibition, although the inhibitory effect of ricin on protein synthesis was more rapid than that of saporin. Moreover, the intrinsic apoptotic pathway was equally activated by both toxins, whilst ricin activated the extrinsic caspase pathway and the effector caspase-3/7 more efficiently than saporin. The complete inhibition of caspases by Z-VAD was only partially effective in cell rescue which appeared to be time limited. Necrostatin-1, a new inhibitor of non-apoptotic death, rescued cells from death by RIPs, although the effect was also partial and temporary. Despite the high RIP doses used no necrosis was detectable by Annexin V/Propidium Iodide (PI) test. These results suggest that more than one death mechanism was elicited by both ricin and saporin, however, with different timing and strength. The perspective of modulating cell death of neoplastic lymphocytes through different pathways could add new opportunities to reduce side effects and develop combined synergic immuno-chemotherapy.


Characteristics of patients with brain metastases receiving trastuzumab for HER2 overexpressing metastatic breast cancer.
The intention of this retrospective analysis was to describe the characteristics of patients with brain metastasis (BM) receiving trastuzumab for HER2 overexpressing metastatic breast cancer (MBC). A specific focus was the relation of BM occurrence to remission status of visceral disease during trastuzumab treatment. Patients with MBC presenting between March 2000 and May 2004 were included in this retrospective analysis. HER2 overexpression was determined by immunohistochemistry (IHC; DAKO Hercep Test). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. Among 136 HER2 overexpressing patients (DAKO score 3+), 42 patients with BM were identified during follow-up (30.9%). Negative hormone receptor expression (estrogen receptor (ER) and progesterone receptor (PgR)) correlated with incidence of BM (42.8% vs. 23.4%; P=0.01). There was no correlation of the development of BM with regard to tumor grading and patient age. In patients who developed BM, the median interval between visceral and brain metastasis was 14 months (range 0-69 months). At the time BM was diagnosed, 14 out of 42 patients responded to trastuzumab-based treatment schedules (OR: 33.3%, 95% CI 18.5-48.2%). Median survival from diagnosis of BM was 13 months (range 0-60 months). The median overall survival calculated from first diagnosis of metastasis was not significantly shorter in patients with BM than in patients without BM (37 vs. 47 months; P=0.07 log rank). Trastuzumab is highly effective for the treatment of liver and lung metastasis in HER2 overexpressing patients, while it is apparently ineffective for treating or preventing BM. Since one third of HER2 overexpressing patients with MBC developed BM despite effective trastuzumab treatment, new treatment strategies and closer surveillance may be warranted for these patients.


Heterogeneity of the interflavanyl bond in proanthocyanidins from natural sources lacking C-4 (C-ring) deoxy flavonoid nucleophiles.
The proanthocyanidin pool in the floral kingdom usually involves the presence of carbon-carbon bonds linking predominantly flavan-3-ol constituent moieties. Such an ensemble of flavan-3-ol units originates via electrophilic aromatic substitution of flavan-4-yl carbocations (or their equivalents) derived from flavan-4-ols and/or flavan-3,4-diols and the nucleophilic centers of the m-oxygenated A-rings of flavan-3-ol nucleophiles. In the absence of these potent flavan-3-ol nucleophiles with their aptitude for the formation of carbon-carbon bonds, alternative centers emerge as participants in interflavanyl bond formation. Such a phenomenon is demonstrated for the distribution of various profisetinidin-, prorobinetinidin-, proguibourtinidin-, promelacacinidin- and proteracacinidin-type pro- and leuco-anthocyanidins in several southern hemisphere heartwood species.


Elucidating the inhibitory mechanisms of the ethanolic extract of the fruiting body of the mushroom Antrodia cinnamomea on the proliferation and migration of murine leukemia WEHI-3 cells and their tumorigenicity in a BALB/c allograft tumor model.
The aim of this study was to explore whether the ethanolic extract of Antrodia cinnamomea (EEAC), a medical mushroom form Taiwan, could affect the proliferation and migration of WEHI-3 cells in vitro and to explore the antitumor effects of EEAC in BALB/c mice engrafted with WEHI-3 cells. The results showed that EEAC inhibited the proliferation of WEHI-3 cells, resulting in the accumulation of cell in G0/G1 and G2/M phases, as determined by flow cytometry. Moreover, EEAC markedly reduced the migration of WEHI-3 cells, as determined by a transwell assay. Treatment of WEHI-3 cells with EEAC also decreased MMP-9 protein expression and enzyme activity. The protein levels of p-Akt, p-ERK1/2 were also decreased, whereas the expression of p21 and p27 was increased. Furthermore, in an in vivo model, EEAC treatment reduced the infiltration of WEHI-3 cells into the liver and spleens and decreased tumor growth. Other bioactive compounds, such as cordycepin and zhankuic acid A, have been demonstrated to reduce the expression of MMP-9, cyclin E, cyclin D1 and to increase the expression of p21, p27. This is the first study to investigate that the mechanisms by which EEAC reduce the proliferation and migration of WEHI-3 cells in vitro, as well as the ability of EEAC to reduced infiltration of WEHI-3 cells into the liver and spleen in vivo. The results suggest that EEAC may prove to be useful in future antileukemic therapies.


Definition of a new HLA-B7 subtype (B*0704) by isoelectric focusing, family studies and DNA sequence analysis.
During screening of potential bone marrow donors, a previously undescribed banding position for the serologically defined HLA-B7 antigen was identified in three unrelated families using one dimensional isoelectric focusing and class I specific Western blot analysis. The isoelectric point of the new variant is more acidic than the two HLA-B7 variants that had been defined before. In each family the new B7 variant was found linked to HLA-A2 and -Cw7. Cloning and sequencing of full-length clones of complementary DNA showed that the new allele (B*0704) differs from B*0702, the common allele encoding HLA-B7, by three nucleotide substitutions within the codon for residue 156 of the mature heavy chain. As a result of these differences amino acid 156 is changed from arginine to aspartic acid, a difference consistent with the isoelectric points. The group of three nucleotide substitutions that distinguish B*0704 from B*0702 is present in other HLA-B alleles.


Demulsification of water-in-crude oil emulsion driven by a carbonaceous demulsifier from natural rice husks.
Removing emulsified water from a water-in-crude oil (W/O) emulsion is critically required prior to downstream processing in the petroleum industry. In this work, environmentally friendly and amphipathic rice husk carbon (RHC) demulsifier was prepared by a simple carbonization process in a muffle furnace using rice husks as starting materials. RHC was characterized by field-emission scanning electron microscope, energy dispersive spectrometer, Fourier transform infrared spectrometer, ultraviolet-visible spectrometer, powder X-ray diffraction, zeta potential and synchronal thermal analyzer. The factors such as dosage, temperature, settling time, pH value and salinity were systematically investigated. The results indicated that the dehydration efficiency (DE) reached as high as 96.99% with 600 mg/L of RHC for 80 min at 70 °C. RHC exhibited an optimal DE under neutral condition, but it was also effective under acidic and alkaline conditions. Also, it had an excellent salt tolerance. The possible demulsification mechanism was explored by interfacial properties, different treatment methods for RHC and microexamination. The demulsification of RHC is attributed to its high interfacial activity, oxygen-containing groups and content of silica. It indicates that RHC is an effective demulsifier for the treatment of the W/O emulsion.


Changes in the range of angular variation of the ankle, knee, hip and neck joints related to the awareness of an impending perturbation.
Challenging quiet standing tasks for the ankle, knee, hip, and neck joints were used to test the effect of pre-cueing on the reaction time of articular stabilization strategies. We assessed balance recovery in 15 subjects who were exposed to backward translations on a movable platform during two conditions: alerted, where participants gazed at a countdown light that pre-cued the onset of the platform translation; and unalerted, without onset time pre-cue. We compared the angular variation of the ankle, knee, hip, and neck joints between the two conditions over four window epochs (0-50 ms; 50-100 ms; 100-150 ms; 150-200 ms). When comparing the window epochs of the ankle and hip joints between conditions, a significant effect was observed in the first and second windows. In the second and third windows, a significant effect was only observed in the alerted group, thereby indicating a faster stability for alerted condition. No significant effect was observed for the knee joint, while a significant effect was observed in the neck joint during the third and fourth windows of the alerted condition. Pre-cueing can modify the synergies of the automatic reactive postural responses, prioritizing the stabilization of main joints such as the ankle and hip over that of the neck and knee. It was suggested that joint stabilization in the hip occurred due to the involuntary anticipation preprogrammed in the cortex by the visual pre-cue.


Biochemical remission and recurrence rate of secreting pituitary adenomas after transsphenoidal adenomectomy: long-term endocrinologic follow-up results.
Transsphenoidal surgery is safe and effective in patients with secreting pituitary adenomas; however, variable outcomes have been reported according to the different criteria used to define the biochemical remission of hormone hypersecretion. We report the long-term endocrinologic follow-up results of a large cohort of patients who underwent TSS for secreting pituitary adenomas according to the most recent stringent criteria of cure. Two hundred ten consecutive patients were operated on by TSS between 1995 and 2004 for a secreting pituitary adenoma (65 PRL-, 109 GH-, and 36 ACTH-secreting adenomas) and were considered for the study. The overall remission rate was 65% for the whole series, being 64%, 61%, and 75% for PRL-, GH-, and ACTH-secreting adenomas, respectively. Eighty-six percent of microadenomas and 53% of macroadenomas were cured by surgery. Remission rates were significantly higher in GH- and ACTH-secreting pituitary macroadenomas than in macroprolactinomas. At a median follow-up of 56 months, tumor recurrence was 0%, 11%, and 14% for GH-, ACTH-, and PRL-secreting tumors. Tumor size, cavernous sinus invasion, and high hormone levels were negatively correlated to the outcome. Transsphenoidal surgery remains an effective treatment for secreting pituitary tumors according to the most recent criteria of cure. Patients with PRL- or ACTH-secreting adenomas may recur after apparently successful surgery, thereby justifying long-term careful endocrinologic follow-up.


Combined treatment of coenzyme Q10 and aprotinin with intraaortic balloon pumping following aorto-coronary bypass surgery.
The effect of combined treatment of coenzyme Q10 (CoQ10) and aprotinin with intra-aortic balloon pumping (IABP) was evaluated in patients who underwent aorto-coronary bypass surgery. Forty-one patients were divided into two groups. Group A (27) were treated by IABP only and Group B (14) were treated by the concomitant use of CoQ10 and aprotinin with IABP. Both groups were subdivided into two groups with regard to the ability to be weaned from IABP (Group A-I, Group B-I) or the inability (Group A-II, Group B-II). CoQ10 was administrated intravenously at doses of 5-10 mg/kg/day and aprotinin was infused at doses 5,000-10,000 KU/kg/day. The percentile incidence of ability to be weaned from IABP was 93 per cent (13/14) in Group B was higher than that of 74 per cent (20/27) in Group A. There were no significant differences among Group A-I, Group A-II, and Group B-I with regard to preoperative and intraoperative factors. Serum GOT and CPK levels on the first postoperative day were significantly higher in Group A-II and Group B-I than those in Group A-I but there was no significant difference between GOT or CPK levels in Group A-II and Group B-I. These results suggest that concomitant treatment of CoQ10 and aprotinin with IABP leads to an improvement in postoperative low cardiac output syndrome.


Controlling Factors and Predictive Models of Total Mercury and Methylmercury Accumulation in Rice (Oryza sativa L.) from Mercury-Contaminated Paddy Soils.
It is urgent to detect the major controlling factors and establish predictive models of mercury (Hg) accumulation in rice. A pot trial was conducted, exogenous Hg was added to 19 paddy soils at 4 concentration levels in this study. The major controlling factors of total Hg (THg) in brown rice were soil THg, pH and organic matter (OM) content, while those of methylmercury (MeHg) in brown rice were soil MeHg and OM. THg and MeHg in brown rice could be well predicted by soil THg, pH and clay content. The data from previous studies were collected to validate the predictive models of Hg in brown rice. The predicted values of Hg in brown rice were within the twofold prediction intervals of the observations, which demonstrated the predictive models in this study were reliable. The results could provide theoretical foundation for the risk assessment of Hg in paddy soils.


The effect of high-dose phenylephrine versus epinephrine on regional cerebral blood flow during CPR.
Prior studies have not found the alpha agonist phenylephrine, in a dose of 0.1 mg/kg, to be as effective as 0.20 mg/kg of epinephrine in improving regional cerebral blood flow (CBF) during CPR in swine. We undertook this study to assess whether higher doses of phenylephrine might improve regional CBF. Fifteen swine were allocated to receive either epinephrine 0.2 mg/kg, phenylephrine 1.0 mg/kg, or phenylephrine 10 mg/kg. Regional CBF measurements were made during normal sinus rhythm, during CPR, and during CPR following drug administration. Epinephrine 0.2 mg/kg was significantly better in improving regional CBF to the left and right cerebral cortices, cerebellum, midbrain, and cervical cord than was phenylephrine 1.0 mg/kg. There was no significant difference in regional CBF between the animals receiving epinephrine 0.2 mg/kg and phenylephrine 10 mg/kg. The study shows that large doses of epinephrine and phenylephrine may be required during CPR to improve regional cerebral blood flow following a prolonged arrest.


The intelligence of rapists: new data.
IQs of violent sexual offenders (rapists) were compared to those of alleged nonviolent sexual offenders, nonsexual violent offenders, and nonsexual nonviolent offenders. Data were gathered from defendants referred to the medical coauthor for pretrial psychiatric evaluation. Rapists scored lower in the IQ test, but this difference did not appear to be significant in the pairwise X2 comparisons. This held true after controlling for the race of the defendant.


Orthodontic elastic band-induced periodontitis - A case report.
Periodontal problems due to the use of elastic bands have been documented in the past. A 9-year-old girl reported to a periodontist with complaints of bleeding from gums and tooth mobility of upper right central incisor. This case, reports the early diagnosis and treatment of an acute localized periodontitis arising from the incorrect use of orthodontic elastic rubber bands to close a maxillary midline diastema. The elastic band induced periodontitis was treated with a combination of surgery, splinting, antibiotics and orthodontics. Removal of the etiologic agent improved the condition of the tooth.


Incidence of ras oncogene activation in lung carcinomas in Hong Kong.
In Hong Kong, lung carcinomas contribute to the majority of cancer deaths among Chinese. Point mutational activation of ras oncogenes has been observed in several populations. The incidence of these mutations in Hong Kong lung carcinomas was investigated. Lung resections obtained from 52 Chinese patients whose conditions were newly diagnosed as non-small cell lung cancer, paraffin sections from 29 Chinese patients with previously diagnosed adenocarcinoma of the lung, and paraffin sections from 49 squamous cell carcinomas were examined for the presence of point mutations in Ki-ras codon 12, N-ras codon 61, and Ha-ras codon 12 oncogenes by allele-specific hybridization after specific amplification of appropriate regions of the DNA using the polymerase chain reaction. Among the 130 lung carcinomas investigated, Ki-ras point mutations were detected in seven cases, of which six were adenocarcinomas and one a squamous cell carcinoma. No mutations were detected in the N-ras and Ha-ras codons. The incidence of Ki-ras codon 12 point mutational activation in Chinese patients with adenocarcinomas was 6 of 63 (9.5%). The incidence of Ki-ras 12 point mutational activation among men with lung adenocarcinomas in Hong Kong (6 of 32 patients, 18.8%) is significantly different from that in women in Hong Kong (0 of 31 patients, 0%). Although ras oncogenes are implicated as having a role in the development of lung adenocarcinomas, especially among smokers, it is clear from these data that they are not associated with the unusually high incidence of lung adenocarcinomas among women in Hong Kong.


Induction and circumvention of nitrate tolerance applying different dosage intervals.
There is increasing evidence that constant nitrate plasma levels, as induced by at least three-times-daily ingestions of isosorbide dinitrate in sustained-release form, lead to an attenuation or even complete loss of the anti-ischemic effects (nitrate tolerance). Therefore, the dependence of tolerance development on dosage intervals according to once-daily and twice-daily ingestions was assessed. Tablets of isosorbide dinitrate (80 mg) in sustained-release form were administered once-daily at 8 A.M. (dosage interval 24 hours) or twice-daily at 8 A.M. and 8 P.M. (dosage interval 12 hours), as well as at 8 A.M. and 2 P.M., respectively (maximal dosage interval 18 hours). A total of 34 patients with angiographically proven coronary artery disease, a history of stable, exercise-dependent angina pectoris, and a reproducible, exercise-induced ST-segment depression of at least 0.15 mV (1.5 mm), who initially showed a response to 80 mg of isosorbide dinitrate, were enrolled. The anti-ischemic effects of isosorbide dinitrate on exercise-induced ischemia were objectively determined by the measurement of exercise-induced ST-segment depression before as well as two, six, and 12 hours after the ingestion at the first and the 15th day of the studies. Since the dosage interval of 12 hours resulted in constant plasma levels, the initially beneficial anti-ischemic effects of isosorbide dinitrate were considerably attenuated after two weeks of treatment. In contrast, the once-daily regimen with its intermittent peaks and valleys of nitrate plasma levels showed identical anti-ischemic effects at the 15th day as compared with the first day. Ingestions at 8 A.M. and 2 P.M. also circumvented the development of nitrate tolerance, however, combined with an even more pronounced anti-ischemic effect after 12 hours as compared with the once-daily regimen. Thus, the circumvention of nitrate tolerance requires a daily "nitrate-poor" interval. The best compromise between a maximal possible anti-ischemic effect and the circumvention of tolerance development was found for the "eccentric" dosage regimen in which the tablets were ingested in the morning and early afternoon.


Energy utilization in the uptake of catecholamines by synaptic vesicles and adrenal chromaffin granules.
Several inhibitors of energy metabolism decreased the ATP-stimulated uptake of catecholamines by isolated synaptic vesicles from rat brain and by chromaffin granules from bovine adrenal medulla. Catecholamine uptake was inhibited by dinitrophenol, S-13 and oleic acid, which are known to block active transport by dissipating trans-membrane proton gradients. Thus a proton gradient appears to be involved in catecholamine transport. Both catecholamine uptake and vesicle-associated Ca2+/Mg2+-ATPase were inhibited by dicyclohexylcarbodiimide and tributyltin, which had previously been shown to inhibit the Ca2+/Mg2+-ATPase of mitochondria. However, mitochondrial ATPase was not involved in catecholamine uptake as oligomycin and aurovertin, more specific inhibitors of mitochondrial ATPase, did not affect catecholamine uptake. It is suggested that ATP stimulates catecholamine uptake by serving as a substrate for the ATPase. Activity of this enzyme causes translocation of protons across the vesicle membrane establishing a trans-membrane proton gradient. The proton gradient drives the transport of catecholamines.


Modification by liposomes of the adenosine triphosphate-activating effect on adenylate deaminase from pig heart.
Adenylate deaminase (AMP deaminase, EC 126.96.36.199) of a high substrate specificity was purified from pig heart by chromatography on cellulose phosphate. The enzyme shows a co-operative binding of AMP [h (Hill coefficient) 2.35, with SO.5 (half-saturating substrate concentration) 5mM]. ATP and ADP act as positive effectors, lowering h to 1.55 and SO.5 to 1 mM. The addition of liposomes (phospholipid bilayers) to ATP-activated or ADP-activated enzyme causes a further shift of the h value to 1.04 and SO.5 to 0.5 mM. For ATP-activated enzyme the addition of liposomes increases Vmax. by about 100%, and for ADP-activated enzyme by 50%. Liposomes have no effect on the kinetics of AMP deaminase in the absence of ATP and ADP, and neither do they influence the inhibitory effect of orthophosphate on heart muscle AMP deaminase. Metabolic implications of these findings are discussed.


Automatic Extraction of Risk Factors for Dialysis Patients from Clinical Notes Using Natural Language Processing Techniques.
Studies have shown that mental health and comorbidities such as dementia, diabetes and cardiovascular diseases are risk factors for dialysis patients. Extracting accurate and timely information associated with these risk factors in the patient health records is not only important for dialysis patient management, but also for real-world evidence generation. We presented HERALD, an natural language processing (NLP) system for extracting information related to risk factors of dialysis patients from free-text progress notes in an electronic dialysis patient management system. By converting semi-structured notes into complete sentences before feeding them into the NLP module, the HERALD system was able achieved 99%, 83% and 80% accuracy in identifying dementia, diabetes and infarction, respectively.


Targeting kidneys by superparamagnetic allopurinol loaded chitosan coated nanoparticles for the treatment of hyperuricemic nephrolithiasis.
The major short coming of conventional therapy system is that they can't deliver the therapeutics specifically to a site within the body without producing nonspecific toxicity. Present research aimed at developing kidney targeted allopurinol (AP) loaded chitosan coated magnetic nanoparticles (A-MNPs) for the management of hyperuricemic nephropathy manifested in the form of nephrolithiasis. The work includes preparation of magnetic nanoparticles by chemical co-precipitation method and evaluation of the prepared batches for particle size analysis, Transmission electron microscopy, entrapment efficiency, in-vitro release study etc. Further, FTIR spectroscopy, X-ray diffraction, Differential Scanning Calorimetry, Vibrational sample magnetometer (VSM) and in-vivo animal studies were also performed. VSM analysis demonstrates that the prepared nanoparticles exhibit superparamagnetic magnetic behaviour which was retained even after coating by chitosan. In-vivo studies of A-MNPs showed 19.07-fold increase in kidney uptake of AP as compared to serum post 2 h of administration in mice whereas no drug was detected in kidney and serum post 2 h administration of pure drug (free-form) indicating successful targeting to kidney as well as sustained release of AP from the formulated A-MNPs. The significant (p < 0.01) effectiveness of A-MNPs in management of hyperuricemic nephrolithiasis was observed through estimating pH and uric acid levels in urine and serum samples of mice. These findings were also confirmed by histological examination of isolated kidney samples. Present investigation signifies that a simple external magnetic field is enough for targeting allopurinol to kidneys by formulating A-MNPs which further offers an effective approach for management of hyperuricemic nephrolithiasis. Graphical Abstract.


Automated radioimmunoassay of nicotine.
We have developed an automated nonequilibrium procedure for the radioimmunoassay of nicotine. The use of a unique iodinated nicotine derivative in this procedure gave a sensitivity of 10 micrograms/l for nicotine with a between-run precision of 7.4% and within-run precision of 6.0%. Nicotine levels of 60 to 67 micrograms/ml were found in subjects 15 min after smoking one standard cigarette. The technique herein reported is a very rapid, and sensitive radioimmunoassay for nicotine and facilitates the determination of nicotine in smoking subjects during the actual process of smoking.


Out-of-plane polarization reversal and changes in in-plane ferroelectric and ferromagnetic domains of multiferroic BiFe0.9Co0.1O3 thin films by water printing.
BiFe0.9Co0.1O3 is a promising material for an ultra-low-power-consumption nonvolatile magnetic memory device because local magnetization reversal is possible through application of an electric field. Here, changes in ferroelectric and ferromagnetic domain structures in a multiferroic BiFe0.9Co0.1O3 thin film induced by "water printing", which is a polarization reversal method involving chemical bonding and charge accumulation at the interface between the liquid and the film, was investigated. Water printing using pure water with pH = 6.2 resulted in an out-of-plane polarization reversal from upward to downward. The in-plane domain structure remained unchanged after the water printing process, indicating that 71° switching was achieved in 88.4% of the observation area. However, magnetization reversal was observed in only 50.1% of the area, indicating a loss of correlation between the ferroelectric and magnetic domains because of the slow polarization reversal due to nucleation growth.


Orthoplatinated triarylphosphite as a highly efficient catalyst for addition reactions of arylboronic acids with aldehydes: low catalyst loading catalysis and a new tandem reaction sequence.
Readily available, air/moisture-stable orthoplatinated triarylphosphite catalyzes the addition reactions of arylboronic acids with aldehydes with the catalyst loading as low as 0.01%. It also cataylzes a new tandem reaction of arylboronic acids with alpha,beta-unsaturated aldehydes to form 1,3-diaryl-1-propanols. Our study provides a new paradigm for the application of orthoplatinated triarylphosphites, and may pave the road to develop other Pt(II) catalysts for such addition reactions and other tandem reactions with such addition reactions as part of the reaction sequence.


Proteins of Nippostrongylus brasiliensis analyzed by immunoblotting.
Antigenic proteins were characterized by the immunoblotting technique with sera from rats and mice after infection as well as hyperimmune sera. The immune response of infected animals was mainly directed toward five proteins of adult worms (190, 118, 110, 98, and 52 kDa) and four proteins of the third larval stage (L3; 92, 78, 58, and 24 kDa). The immunoblots indicated that stage-specific proteins of the homogenates were recognized. Three stage-specific proteins of L3 larvae (150, 135, and 125 kDa) and three proteins typical to the adult worm (100, 82, and 67 kDa) were identified. The majority of the worm proteins elicited an IgG response. IgE synthesis was induced by living and dead parasites and was directed towards four proteins (190, 150, 125, and 98 kDa). Three proteins additionally induced an IgG or IgM antibody response. The immune response as shown by the immunoblotting technique seems to be directed towards (1) antigens that are present for the duration of an infection and (2) stage-specific antigens that are expressed for only a short time during the life cycle of the parasite.