Neurofibromatosis of the head and neck: classification and surgical management.
Neurofibromatosis is common and presents with variable penetrance and manifestations in one in 2500 to one in 3000 live births. The management of these patients is often multidisciplinary because of the complexity of the disease. Plastic surgeons are frequently involved in the surgical management of patients with head and neck involvement. A 20-year retrospective review of patients treated surgically for head and neck neurofibroma was performed. Patients were identified according to International Classification of Diseases, Ninth Revision codes for neurofibromatosis and from the senior author's database. A total of 59 patients with head and neck neurofibroma were identified. These patients were categorized into five distinct, but not exclusive, categories to assist with diagnosis and surgical management. These categories included plexiform, cranioorbital, facial, neck, and parotid/auricular neurofibromatosis. A surgical classification system and clinical characteristics of head and neck neurofibromatosis is presented to assist practitioners with diagnosis and surgical management of this complex disease. The surgical management of the cranioorbital type is discussed in detail in 24 patients. The importance and safety of facial nerve dissection and preservation using intraoperative nerve monitoring were validated in 16 dissections in 15 patients. Massive involvement of the neck extending from the skull base to the mediastinum, frequently considered inoperable, has been safely resected by the use of access osteotomies of the clavicle and sternum, muscle takedown, and brachial plexus dissection and preservation using intraoperative nerve monitoring. Therapeutic, IV.


Long-Term Exposure to American and European Movies and Television Series Facilitates Caucasian Face Perception in Young Chinese Watchers.
Most young Chinese people now learn about Caucasian individuals via media, especially American and European movies and television series (AEMT). The current study aimed to explore whether long-term exposure to AEMT facilitates Caucasian face perception in young Chinese watchers. Before the experiment, we created Chinese, Caucasian, and generic average faces (generic average face was created from both Chinese and Caucasian faces) and tested participants' ability to identify them. In the experiment, we asked AEMT watchers and Chinese movie and television series (CMT) watchers to complete a facial norm detection task. This task was developed recently to detect norms used in facial perception. The results indicated that AEMT watchers coded Caucasian faces relative to a Caucasian face norm better than they did to a generic face norm, whereas no such difference was found among CMT watchers. All watchers coded Chinese faces by referencing a Chinese norm better than they did relative to a generic norm. The results suggested that long-term exposure to AEMT has the same effect as daily other-race face contact in shaping facial perception.


A Neurophysiological Perspective on a Preventive Treatment against Schizophrenia Using Transcranial Electric Stimulation of the Corticothalamic Pathway.
Schizophrenia patients are waiting for a treatment free of detrimental effects. Psychotic disorders are devastating mental illnesses associated with dysfunctional brain networks. Ongoing brain network gamma frequency (30-80 Hz) oscillations, naturally implicated in integrative function, are excessively amplified during hallucinations, in at-risk mental states for psychosis and first-episode psychosis. So, gamma oscillations represent a bioelectrical marker for cerebral network disorders with prognostic and therapeutic potential. They accompany sensorimotor and cognitive deficits already present in prodromal schizophrenia. Abnormally amplified gamma oscillations are reproduced in the corticothalamic systems of healthy humans and rodents after a single systemic administration, at a psychotomimetic dose, of the glutamate N-methyl-d-aspartate receptor antagonist ketamine. These translational ketamine models of prodromal schizophrenia are thus promising to work out a preventive noninvasive treatment against first-episode psychosis and chronic schizophrenia. In the present essay, transcranial electric stimulation (TES) is considered an appropriate preventive therapeutic modality because it can influence cognitive performance and neural oscillations. Here, I highlight clinical and experimental findings showing that, together, the corticothalamic pathway, the thalamus, and the glutamatergic synaptic transmission form an etiopathophysiological backbone for schizophrenia and represent a potential therapeutic target for preventive TES of dysfunctional brain networks in at-risk mental state patients against psychotic disorders.


[Accumulation and biodegradation of anthracene by Chlorella protothecoides under different trophic conditions].
The bioaccumulation and degradation of anthracene by the green alage(Chlorella prothecoides) under autotrophic and heterotrophic conditions were studied. About 29% and 20% of anthracene(original concentration 1.0 mg.L-1) were degraded by light and by Chlorella protothecoides under the autotrophic condition, respectively. About 33.53% of anthracene (original concentration 2.5 mg.L-1) were degraded by C. protothecoides under the heterotrophic condition. The resistance and degradation ability of C. protothecoides under the heterotrophic condition was higher than that under the autotrophic conditions. More than 80% of residual anthracene was accumulated by algal cell under the two conditions. The bioaccumulation factor were 9064 and 1899, under the autotrophic and heterotropnic conditions, respectively. The net accumulation of anthracene, however, was much higher under the heterotropnic condition (202.29 micrograms) than that under the autotrophic condition (69.687 micrograms).


Current challenges in the management of follicular lymphoma.
Although typically indolent in nature, follicular lymphoma remains an ongoing challenge for practicing oncologists. While response rates >90% can be achieved with rituximab-based chemoimmunotherapy in advanced stage patients, the complete remission rates are substantially lower and patients inevitably relapse. The inability to achieve a complete remission and an early progression of disease have recently been determined to be indicative of poorer long-term outcomes. A greater understanding of the pathogenesis of follicular lymphoma has enabled the development of targeted therapies, which may improve standard treatment approaches. Examples include lenalidomide and obinutuzumab, which are currently in front-line Phase III investigation. Other therapies of interest include small molecule inhibitors, immune checkpoint inhibitors and chimeric antigen receptor T cells.


Assessment of effects of propranolol on portal hemodynamics in cirrhosis by duplex ultrasonography.
To study the effect of propranolol on portal hemodynamics in cirrhotics using duplex ultrasonography. Portal venous flow was measured by duplex ultrasonography in 12 healthy volunteers and ten men with cirrhosis. The cirrhotics were evaluated prior to and after ingestion of propranolol (60 mg twice daily for seven days) or placebo in a randomized cross-over fashion. Variations in heart rate, blood pressure, portal vein diameter, and portal venous flow and velocity were evaluated. The mean (SD) portal venous flow in the volunteers was 746 (280) mL/min, portal flow velocity was 18.5 (3.6) cm/s and portal vein diameter was 9.2 (1.4) mm. In cirrhotics, propranolol decreased portal blood flow from 586 (220) to 413 (120) mL/min (p < 0.03), the overall reduction being 29.5%. This effect was due to decrease in portal flow velocity, from 12.5 (3.3) to 9.7 (2.3) cm/s (p < 0.03) without significant change in portal vein diameter. No changes were observed with placebo. Propranolol decreases portal flow velocity and thus portal venous flow in cirrhotics.


Surgery residents and attending surgeons have different perceptions of feedback.
Feedback plays an important role in Postgraduate Medical Education and is indispensable in surgical training. Improvement in operating skills, for example, requires constant feedback between teacher and learner to promote reflection on performance. Prior to providing workshops on giving effective feedback, the goal of this study was to assess the perceptions of attending surgeons and residents on feedback practices in our program. We show a startling disparity in perceptions of feedback frequency and skills. The results were used in planning a Workshop on Giving Feedback for our faculty. The effectiveness of this Workshop will be assessed at a later date by administering the same questionnaire.


Mid-frequency acoustic propagation in shallow water on the New Jersey shelf. II. Intensity fluctuation.
The scintillation index and the intensity cumulative distribution function of mid-frequency (2-10 kHz) sound propagation are presented at ranges of 1-9 km in a shallow water channel. The fluctuations are due to water column sound speed variability. It is found that intensity is only correlated over a narrow frequency band (50-200 Hz) and the bandwidth is independent of center frequency and range. Furthermore, the intensity probability distribution peaks at zero for all frequencies, and follows an exponential distribution at small values.


Effect of methylglucamine salts of iocarmic and iothalamic acids on hemodynamics, acid-base equilibrium and coagulation.
The effects of electrolytes, osmolality, pH, PaO2, PaCO2, hematocrit, blood volume and coagulation occurring after a rapid intra-aortic injection of a monomer and a dimer (salts of methylglucamine of the iothalamic and iocarmic acids) were compared. The effects of the monomer agreed with previous results but the effects of the dimer differed from those reported in the literature.


The effect of changes in criterion value on differential reinforcement of low rate schedule performance.
The differential reinforcement of low rate (DRL) schedule is commonly used to assess impulsivity, hyperactivity, and the cognitive effects of pharmacological treatments on performance. A DRL schedule requires subjects to wait a certain minimum amount of time between successive responses to receive reinforcement. The DRL criterion value, which specifies the minimum wait time between responses, is often shifted towards increasingly longer values over the course of training. However, the process invoked by shifting DRL values is poorly understood. Experiment 1 compared performance on a DRL 30-s schedule versus a DRL 15-s schedule that was later shifted to a DRL 30-s schedule. Dependent measures assessing interresponse time (IRT) production and reward-earning efficiency showed significant detrimental effects following a DRL schedule transition in comparison with the performance on a maintained DRL 30-s schedule. Experiments 2a and 2b assessed the effects of small incremental changes vs. a sudden large shift in the DRL criterion on performance. The incremental changes produced little to no disruption in performance compared to a sudden large shift. The results indicate that the common practice of incrementing the DRL criterion over sessions may be an inefficient means of training stable DRL performance.


Chemical constituents from the leaves of Pinus dalatensis Ferré.
A phytochemical study of n-hexane and ethyl acetate extracts of Pinus dalatensis Ferré leaves led to the isolation of 11 compounds, including one caryolane sesquiterpenoid (1), five labdane diterpenoids (2, 3, 4, 5, 6), one serratane triterpenoid (7), one diacylated flavonoid glucoside (8), one stilbenoid (9) and two sterols (10, 11). The structural characterisation of the isolated compounds was elucidated by spectroscopic data and comparison with the literature report on the chemical constituents from Pinus dalatensis Ferré. Futhermore, three compounds 1, 4 and 6 were obtained for the first time from the genus Pinus. Besides, compounds (2, 3, 5, 8, 9) were also subjected to cytotoxicity effect on SK-LU-1, MCF-7 and Hep-G2 cell lines, but only compound 9 expressed activities with IC50 values of 141.22, 127.81 and 166.84 μM, respectively.


Antibiotic therapy and 48-hour mortality for patients with pneumonia.
Although numerous articles have demonstrated that recommended empiric antimicrobial regimens are associated with decreased mortality at 30 days, there is controversy over whether appropriate antibiotic selection has a beneficial impact on mortality within the first 48 to 96 hours after admission. Our aim was to determine whether the use of guideline-concordant antibiotic therapy is associated with decreased mortality within the first 48 hours after admission for patients with pneumonia. A retrospective cohort study was conducted at two tertiary teaching hospitals in San Antonio, Texas. A propensity score was used to balance the covariates associated with the use of guideline-concordant antimicrobial therapy. A multivariable logistic regression model was used to assess the association between mortality within 48 hours and the use of guideline-concordant antibiotic therapy, after adjusting for potential confounders including the propensity score. Information was obtained on 787 patients with community-acquired pneumonia. The median age was 60 years, 79% were male, and 20% were initially admitted to the intensive care unit. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. Within the first 48 hours, 20 patients died. After adjustment for potential confounders, the use of guideline-concordant antimicrobial therapy (odds ratio 0.37, 95% confidence interval, 0.14-0.95) was significantly associated with decreased mortality at 48 hours after admission. Using initial empiric guideline-concordant antimicrobial therapy is associated with decreased mortality at 48 hours. Further research needs to investigate methods to ensure that patients with community-acquired pneumonia are treated with appropriate antimicrobial therapies.


The effects of estrogen on single dose dimethylnitrosamine carcinogenesis in male inbred Crl/CDF rats.
The effect of longterm estrogen treatment (estradiol valerate) on male rats injected i.p. once with dimethylnitrosamine (DMN, 30 mg/kg, with protein starvation), was studied in 167 male inbred Crl/CDF rats. DMN was given at 40 days (immature rats) or at 90 days (mature rats) to investigate the action of carcinogen and hormone at different stages of development. Estrogen reduced life expectancy of male animals, and was associated with greatly increased breast tumour incidence (to 30%) compared with controls (3%, p less than 0.01). DMN alone enhanced lung tumorigenesis (p less than 0.001) and chronic estrogen treatment significantly reduced both the incidence and multiplicity of DMN-induced lung tumours in male rats (p less than 0.001). Also, estrogen treatment lowered the incidence of spontaneous lung tumours (p less than 0.005). The higher incidence of animals with kidney tubular adenomas and carcinomas induced by DMN in both mature and immature rats was statistically significant (p less than 0.001), but estrogen and the age at carcinogen treatment had no effect. Lethal mesenchymal kidney tumours developed in immature rats exposed to DMN (p less than 0.001), but only developed in mature DMN-treated rats if they received estrogen as well.


Z-Shaped Transfer Functions for Binary Particle Swarm Optimization Algorithm.
Particle swarm optimization (PSO) algorithm is a swarm intelligent searching algorithm based on population that simulates the social behavior of birds, bees, or fish groups. The discrete binary particle swarm optimization (BPSO) algorithm maps the continuous search space to a binary space through a new transfer function, and the update process is designed to switch the position of the particles between 0 and 1 in the binary search space. Aiming at the existed BPSO algorithms which are easy to fall into the local optimum, a new Z-shaped probability transfer function is proposed to map the continuous search space to a binary space. By adopting nine typical benchmark functions, the proposed Z-probability transfer function and the V-shaped and S-shaped transfer functions are used to carry out the performance simulation experiments. The results show that the proposed Z-shaped probability transfer function improves the convergence speed and optimization accuracy of the BPSO algorithm.


Five-Repetition Sit-to-Stand Test: Responsiveness and Minimal Important Difference in Idiopathic Pulmonary Fibrosis.
Standing from a sitting position is an important activity of daily living. The five-repetition sit-to-stand test (5STS) is a simple physical performance test that measures the fastest time taken to stand five times from a chair with arms folded. It can be measured in most healthcare settings, including the home where traditional field walking tests may not be possible. The 5STS has been validated in community-dwelling older adults and people with COPD, but data in idiopathic pulmonary fibrosis (IPF) are limited. The aims of this cohort study were to establish the construct validity, responsiveness to pulmonary rehabilitation (PR) and minimal important difference (MID) of the 5STS in IPF. In 149 people with IPF, we compared 5STS to measures of lung function, exercise capacity, quadriceps strength, breathlessness and health-related quality of life. Responsiveness and effect sizes were determined by measuring 5STS before and after PR. The MID was estimated using anchor- and distribution-based methods. The 5STS correlated significantly with incremental shuttle walk test (ISW) (r=-0.55), isometric quadriceps maximum voluntary contract (QMVC) (r=-0.45), Medical Research Council (MRC) score (r=0.40), Chronic Respiratory Questionnaire (CRQ)-Total (r=-0.21) and King's Brief Interstitial Lung Disease-Total (r=-0.21) but not forced vital capacity %predicted or quadriceps 1-repetition maximum (1RM). There was a significant but very weak correlation between change in 5STS and change in MRC (r=0.18), ISW (r=-0.21) and CRQ-Total (r=-0.26) but no significant correlation with change in 1RM (-0.12) or QMVC (r=-0.18). 5STS time improved with PR (median (25th, 75th centile) change: -1.97 (-3.47, -0.62) seconds; p<0.001). The effect size for 5STS was 0.66 and higher than quadriceps 1RM, QMVC and ISW. The mean (range) MID estimate was -1.93 (-1.85 to -2.10) seconds. In people with IPF, the 5STS is a valid physical performance measure that is responsive to exercise-based interventions and suitable for use in most healthcare settings.


Sources of atmospheric black carbon and related carbonaceous components at Rishiri Island, Japan: The roles of Siberian wildfires and of crop residue burning in China.
A field study was conducted to clarify sources of atmospheric black carbon and related carbonaceous components at Rishiri Island, Japan. We quantified equivalent black carbon (eBC) particle mass and the absorption Ångström exponent (AAE), atmospheric CO and CH4, in addition to levoglucosan in total suspended particles, a typical tracer of biomass burning. Sixteen high eBC events were identified attributable to either anthropogenic sources or biomass burning in Siberia/China. These events were often accompanied by increases of co-emitted gases such as CH4 and CO. Specifically, we observed pollution events with elevated eBC, AAE, levoglucosan, and CH4CO slope in late July 2014, which were attributed to forest fires in Siberia by reference to the FLEXPART model footprint and fire hotspots. In autumn, drastic increases of eBC, AAE, and levoglucosan were observed, accompanied by an eBC-CO slope of >15 ng m-3/ppb, resulting from long-range transport of emissions from extensive burning of crop residue on the Northeast China Plain. Other than the sources of fossil fuel combustion in China and forest fires in Siberia, we report for the first time that pollution events in northern Japan are caused by crop residue burning in China. This study elucidated valuable information that will improve understanding of the effects of biomass burning in East Asia on atmospheric carbonaceous components.


Selection of Optimum Strategies for the Fabrication of Plant-Mediated Metal Nanoparticles: Emerging Problems in Sustainability.
The green fabrication of nanoparticles (NPs) by using plants as reducing and capping agents involves energy efficient, less toxic, safer and simpler pathways. These pathways have been related to the rational use of numerous substances in fabrication of NPs and synthetic strategies, which have been mainly discussed in this article. The subject matter of this review is to discuss how a chemist can follow the green chemistry principles in terms of selection of substances and protocols used for NPs fabrication. Furthermore, it describes how a researcher can modify the physical properties of NPs by varying the reaction conditions. In short, this review article provides a scheme for the synthesis of NPs from selection of suitable plant to characterization of formed NPs by employing green chemistry.


Increased bile resistance in Salmonella enterica mutants lacking Prc periplasmic protease.
Prc is a periplasmic protease involved in processing of penicillin-binding protein 3 (PBP3). Lack of Prc suppresses bile sensitivity in Dam-, Wec-, PhoP-, DamX-, and SeqA- mutants of Salmonella enterica, and increases bile resistance in the wild type. Changes in the activity of penicillin binding proteins PBP3, PBP4, PBP5/6 and PBP7 are detected in a Prc- background, suggesting that peptidoglycan remodeling might contribute to bile resistance.


Developments in judicial approaches to sexual and reproductive health.
This article reviews the jurisprudence on reproductive and sexual health of national and international tribunals. This review reveals a shift from controlling reproduction and sexuality through the use of criminal law to impose a moral order, to the use of administrative law to ensure availability of safe and effective services, and, finally, to the use of human rights to promote respect for human dignity. The conventional use of criminal law to prohibit provision of reproductive and sexual health services, underage sex, and relations between same-sex partners is waning. Due in part to research showing how criminal law harms reproductive health, an emerging judicial trend is toward the more pragmatic use of law to reduce the harm to health associated with sexuality and reproduction. Most recently, courts are recognizing that respect for individuals' needs to protect their reproductive and sexual health is a matter of social justice.


Time-resolved thermal lens investigation of glassy dynamics in supercooled liquids: Theory and experiments.
This work reports results on the simultaneous spectroscopy of the specific heat and thermal expansivity of glycerol by making use of a wideband time-resolved thermal lens (TL) technique. An analytical model is presented which describes TL transients in a relaxing system subjected to impulsive laser heating. Experimentally, a set of TL waveforms, from 1 ns to 20 ms, has been recorded for a glycerol sample upon supercooling, from 300 to 200 K. The satisfactory fitting of the TL signals to the model allows the assessment of relaxation strength and relaxation frequency of the two quantities up to sub-100 MHz, extending the specific heat and thermal expansion spectroscopy by nearly three and eight decades, respectively. Fragility values, extracted from the relaxation behavior of the specific heat and the thermal expansion coefficient, are found to be similar, despite a substantial difference in relaxation strength.


Pocket proteins and cell cycle regulation in inner ear development.
Loss of neurosensory cells of the ear, caused by genetic and non-genetic factors, is becoming an increasing problem as people age, resulting in deafness and vestibular disorders. Unveiling useful mechanisms of cell cycle regulation may offer the possibility to generate new cells out of remaining ones, thus providing the cellular basis to induce new hair cell differentiation in the mammalian ear. Here, we provide an overview of cell cycle regulating genes in general and of those studied in the ear in particular. We categorize those genes into regulators that act upstream of the pocket proteins and into those that act downstream of the pocket proteins. The three members of the pocket protein family essentially determine, through interaction with the eight members of the E2F family, whether or not the cell cycle will progress to the S-phase and thus cell division. The abundant presence of one or more members of these families in adult hair cells supports the notion that inhibition of cell cycle progression through these proteins is a lifelong process. Indeed, manipulating some of those proteins, unfortunately, leads to abortive entry into the cell cycle. Combined with recent success to induce hair cell differentiation through molecular therapy, these approaches may provide a viable strategy to restore lost hair cells in the inner ear.


Effect of lipids and proteins on the viscosity of gastric mucus glycoprotein.
The effect of associated lipids and covalently bound fatty acids, and the contribution of serum albumin and secretory IgA to the viscosity of dog gastric mucus glycoprotein was investigated. Using a cone/plate viscometer at shear rates between 1.15 - 230s -1, it was found that extraction of associated lipids from the glycoprotein lead to 80-85% decrease in the viscosity. Further loss (39%) in viscosity of the delipidated glycoprotein occurred following removal of covalently bound fatty acids. Reassociation of the delipidated glycoprotein with its neutral lipids increased the viscosity 3-fold, a 2.5-fold increase was obtained with glycolipids, and 2-fold with phospholipids. Preincubation of purified mucus glycoprotein with albumin or IgA resulted in the increase in viscosity. This increase in viscosity was proportional to albumin concentration up to 10%, and to IgA concentration up to 5%. The results show that interaction of lipids and proteins with mucus glycoprotein contributes significantly to the viscosity of gastric mucus.


Simple, scalable, and ultrasensitive tip-based identification of protease substrates.
Proteases are in the center of many diseases, and consequently, proteases and their substrates are important drug targets as represented by an estimated 5-10% of all drugs under development. Mass spectrometry has been an indispensable tool for the discovery of novel protease substrates, particularly through the proteome-scale enrichment of so-called N-terminal peptides representing endogenous protein N termini. Methods such as combined fractional diagonal chromatography (COFRADIC)1 and, later, terminal amine isotopic labeling of substrates (TAILS) have revealed numerous insights into protease substrates and consensus motifs. We present an alternative and simple protocol for N-terminal peptide enrichment, based on charge-based fractional diagonal chromatography (ChaFRADIC) and requiring only well-established protein chemistry and a pipette tip. Using iTRAQ-8-plex, we quantified on average 2,073 ± 52 unique N-terminal peptides from only 4.3 μg per sample/channel, allowing the identification of proteolytic targets and consensus motifs. This high sensitivity may even allow working with clinical samples such as needle biopsies in the future. We applied our method to study the dynamics of staurosporine-induced apoptosis. Our data demonstrate an orchestrated regulation of specific pathways after 1.5 h, 3 h, and 6 h of treatment, with many important players of homeostasis targeted already after 1.5 h. We additionally observed an early multilevel modulation of the splicing machinery both by proteolysis and phosphorylation. This may reflect the known role of alternative splicing variants for a variety of apoptotic genes, which seems to be a driving force of staurosporine-induced apoptosis.


Fabrication of Gelatin Methacrylate (GelMA) Scaffolds with Nano- and Micro-Topographical and Morphological Features.
The design of biomimetic biomaterials for cell culture has become a great tool to study and understand cell behavior, tissue degradation, and lesion. Topographical and morphological features play an important role in modulating cell behavior. In this study, a dual methodology was evaluated to generate novel gelatin methacrylate (GelMA)-based scaffolds with nano and micro topographical and morphological features. First, electrospinning parameters and crosslinking processes were optimized to obtain electrospun nanofibrous scaffolds. GelMA mats were characterized by SEM, FTIR, DSC, TGA, contact angle, and water uptake. Various nanofibrous GelMA mats with defect-free fibers and stability in aqueous media were obtained. Then, micropatterned molds produced by photolithography were used as collectors in the electrospinning process. Thus, biocompatible GelMA nanofibrous scaffolds with micro-patterns that mimic extracellular matrix were obtained successfully by combining two micro/nanofabrication techniques, electrospinning, and micromolding. Taking into account the cell viability results, the methodology used in this study could be considered a valuable tool to develop patterned GelMA based nanofibrous scaffolds for cell culture and tissue engineering.


Atrial Fibrillation on Admission Is Related With Higher Mortality in ST-Segment Elevation Myocardial Infarction Patients.
The prognostic significance of atrial fibrillation (AF) on mortality in ST-segment elevation myocardial infarction (STEMI) patients is not clearly understood. To elucidate the clinical significance of AF on mortality for 1 year in STEMI patients, we retrospectively analyzed the Korea Acute Myocardial Infarction Registry (KAMIR) database, which spans January 2008 to September 2010 and includes 14,329 patients with acute myocardial infarction. We selected 5,556 patients with marked ECG rhythm (NSR, normal sinus rhythm or AF) on emergency room arrival, < 12 hours of symptom onset, and who underwent primary percutaneous coronary intervention (PCI) within 90 minutes of arriving at the hospital. Patients who had been followed-up for at least for 1 year were analyzed (2,636 of NSR, 119 of AF). At enrollment, AF patients were older (70.7 versus 65.5 years, P < 0.001) and had lower systolic blood pressure (120.6 versus 125.9 mmHg, P = 0.050), a higher heart rate (80.4 versus 75.6/minute, P = 0.009), and a higher rate of Killip III, IV (25.0 versus 14.2%, P = 0.002). Patients with AF showed clearly higher all-cause mortality (22.7 versus 9.5%, HR 2.51, 95%CI 1.68~3.76, P < 0.001) and cardiac death rate (17.7 versus 7.5%, HR 2.49, 95%CI 1.59~3.90, P < 0.001) at 1 year after admission compared patients with NSR. AF induced significantly higher all-cause mortality and cardiac mortality rate in STEMI patients who were appropriately revascularized with primary PCI compared to NSR at 1 year.


Design, Synthesis and Evaluation of Praziquantel Analogues and New Molecular Hybrids as Potential Antimalarial and Anti-Schistosomal Agents.
Malaria and schistosomiasis are two of the neglected tropical diseases that persistently wreak havoc worldwide. Although many antimalarial drugs such as chloroquine are readily available, the emergence of drug resistance necessitates the development of new therapies to combat this disease. Conversely, Praziquantel (PZQ) remains the sole effective drug against schistosomiasis, but its extensive use raises concerns about the potential for drug resistance to develop. In this project, the concept of molecular hybridization was used as a strategy to design the synthesis of new molecular hybrids with potential antimalarial and antischistosomal activity. A total of seventeen molecular hybrids and two PZQ analogues were prepared by coupling 6-alkylpraziquanamines with cinnamic acids and cyclohexane carboxylic acid, respectively. The synthesised compounds were evaluated for their antimalarial and antischistosomal activity; while all of the above compounds were inactive against Plasmodium falciparum (IC50 > 6 µM), many were active against schistosomiasis with four particular compounds exhibiting up to 100% activity against newly transformed schistosomula and adult worms at 50 µM. Compared to PZQ, the reference drug, the activity of which is 91.7% at 1 µM, one particular molecular hybrid, compound 32, which bears a para-isopropyl group on the cinnamic acid moiety, exhibited a notable activity at 10 µM (78.2% activity). This compound has emerged as the front runner candidate that might, after further optimization, hold promise as a potential lead compound in the fight against schistosomiasis.


Two Magnetic Switching Complexes Based on the Fe(II) Ion.
Two neutral mononuclear iron(II) complexes with different spin-crossover (SCO) properties, Fe(L1)2(SCN)2 (1) and Fe(L2)2(SCN)2 (2) (L1 = 2-(thiophen-3-yl)-1H-imidazo[4,5-f][1,10]phenanthroline and L2 = 2-(thiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline), were solvothermally synthesized. With the different substituted position in 1,10-phenanthroline derivatives, 1 exhibits gradual SCO around room temperature with T1/2 = 280 K, while 2 displays abrupt SCO with 10 K hysteresis at T1/2↓ = 210 K and T1/2↑ = 220 K.


Attitudes of Greek dentists towards repair of conservative restorations. An online survey.
Repair versus replacement of a defective direct restoration is one important step for conserving tooth structure. This study was designed to collect information on the attitudes of Greek dentists towards repairing direct restorations. An electronic questionnaire with 16 multiple-choice and rank-ordering questions was created online and its URL address was randomly emailed to 800 dentists in the area of Athens, Greece. The questionnaire remained open for 3 months, and after two reminder emails the data collected were analysed statistically to identify differences between clinician's sex or years of practicing dentistry, using the chi-square and Kruskal-Wallis tests at α = 0.05. Three-hundred and twenty dentists completed and submitted the questionnaire (response rate = 40%). A high proportion (86.8%) of the respondents reported that they routinely repair defective restorations, ranking the order of their frequency as 2.47 for amalgam and 2.41 for resin restorations. The reasons, with the highest ranks, for repairing amalgams were the restoration of bulk fractures (4.10) and restoration of marginal fractures (3.69). For repair of resin restorations, the reasons with the highest ranks were improving their colour (4.04) and removing marginal discoloration (3.99). Moreover, 94.1% of the respondents stated that they were enough, much and very much satisfied with the repair, 1 year after it was performed. A high percentage of Greek dentists are repairing defective direct restorations. There are discrepancies in the indications, techniques and materials used for repairs, such as bulk fractures and marginal restorations. Further studies on the efficacy of repairs, the criteria and procedure protocols are needed. Further, additional clinical education should be offered at the undergraduate or continuing education levels.


New method for correction of lumbo-sacral kyphosis deformity in patient with high pelvic incidence.
Technical note. We describe a novel technique of bilateral longitudinal sacral osteotomy allowing direct reduction of high pelvic incidence (PI) and correction of sagittal imbalance. A 25-year-old female patient presented with a disabling lumbo-sacral kyphosis fused in situ through previous operations with residual low-grade wound infection and grade IV L5/S1 spondylolisthesis with severity index (SI) of 65%. A two-stage correction was performed. First anterior in situ fixation of the L4-L5-S1 segments was performed using a hollow modular anchorages (HMA) screw and L3/L4 anterior interbody cage. The second stage consisted of instrumentation of the lower lumbar spine and pelvis; placement of an S1 transverse K-wire as pivot point and bilateral longitudinal sacral osteotomy which allowed for gradual retroversion of the central sacrum relative to the pelvis. Sacrum was derotated by 30° which allowed to restore spinal sagittal balance and decrease SI by 15%. Postoperative recovery was complicated by a flare up of the pre-existing deep wound infection. Bilateral longitudinal sacral osteotomy appears to be a safe and efficient way of correcting the sagittal imbalance caused by an extremely high PI. Although technically demanding, it achieves good radiological and functional outcomes and avoids entering the spinal canal.


Photobiomodulation in the treatment of chronic non-responding wounds.
We present a protocol of care and therapeutic approach to skin lesions, called AIMED (Anti Inflammatory Regenerative Medicine), which is based on the circularity of its phases and applied therapeutic methodologies. We used photobiomodulation (PBM) for the examination non-responding skin lesions. PBM is an adjuvant treatment for the stimulation of regenerative cellular processes, reduction of inflammation and pain and biochemical modulation of molecular response. We used PBM for the examination of skin lesions, which were not responding to other therapies. LumiHealTM protocol treatment has been applied for 3 months on 8 patients affected by infected vascular ulcers of the lower limbs resistant to previous treatments. Three patients reached positive results immediately, and the remaining 5, at the first follow-up. The use of LumiHealTM in combination with other treatments, method allowed an effective and rapid improvement of the lesions via modulation of the immune response.


Secondary-sites for integration mediated by the Tn21 integrase.
The integrase encoded by the integron of the transposon Tn21 can mediate the site-specific fusion of two plasmids if there is a recombination hot spot (59 bp element) in one of them and the sequence GWTMW in the other. The use of this latter, loosely defined site explains how antibiotic-resistance genes could first become associated with integrons.


Molecular alignment of rigid rods in nonrigid spherical pores.
We have investigated the orientation ordering of two shish-kebab chains confined by spherically harmonic potentials through Monte Carlo simulations and asymptotic analysis. The rigid rod is modeled as shish-kebab chains consisting of tangent hard spheres aligned in the same axis, and the harmonic potential is chosen to model nonrigid cavities. We first show that the interactions between a rod and the spherically harmonic potential are independent of chain orientation, indicating that the alignment of two confined rods arises from the excluded volume interactions alone. In the strong fields, the order parameter of two confined rods converges to different values, depending on the parity of chain length. From asymptotic order parameters, we find that the rods of odd-number beads rotate more freely even under the limiting strong confinement. However, the two rods of even-number beads are essentially trapped in a configuration of perpendicular alignment through intercalation of their central grooves. We attribute the dependence of the parity of chain length to the different locations of the center-of-mass in a rod for these two cases. Furthermore, we compare the shish-kebab chains with different rod models in the simulations, and utilize these models to explore the effect of the local rod smoothness on molecular alignment. Our findings suggest that increasing local rod smoothness enhances the rotational degree of freedom for confined rods, and the effect of local rod roughness emerges under strong enough applied potentials.


Construction of Indole-Fused Seven- and Eight-Membered Azaheterocycles via a Tandem Pd/NBE-Catalyzed Decarbonylation and Dual C-H Activation Sequence.
Herein, we report the transformation of aromatic acids to indole-fused seven- and eight-membered azaheterocycles. Two C-C bonds are formed via the cleavage of one C-C bond and two C-H bonds. The incorporation of indole moieties into bioactive pharmaceuticals and natural products to construct a medium-sized polyfused heterocycle demonstrates the synthetic utility of the protocol.


Identification of the Fungal Community in Otomycosis by Internal Transcribed Spacer Sequencing.
We used internal transcribed spacer (ITS) sequencing to identify the fungal community in otomycosis patients and to evaluate the treatment effects of bifonazole. Ten patients who visited the Department of Otolaryngology of Jiangsu Provincial Hospital on Integration of Chinese and Western Medicine from May 2020 to April 2021 were recruited. Otomycosis patients were treated with bifonazole solution once a day for 14 days. Samples collected from the external auditory canal before and after treatment (Pre-treatment, n = 14 ears; Post-treatment, n = 14 ears) were used for microscopic examination, fungal culture, and ITS sequencing. Samples collected from 10 volunteers (Control, n = 20 ears) were used as controls. The symptoms, including ear itching, aural fullness, otalgia, hearing loss, and physical signs were recorded before treatment as well as on the 7th and 14th days after treatment. Aspergillus was identified as a main pathogenic fungus by microscopic examination, fungal culture, and ITS sequencing. At the genus level, Aspergillus was more abundant in the pre-treatment group than the control and post-treatment groups, and Malassezia was more abundant in the control and post-treatment groups than the pre-treatment group. The fungal species richness and diversity reduced significantly in the pre-treatment group compared with the control and post-treatment groups. The effective rate of bifonazole was 64.29% and 100% on the 7th and 14th days after treatment, respectively. In conclusion, the results obtained from morphologic studies and ITS sequencing indicate that Aspergillus is the main pathogenic fungus of otomycosis patients in Nanjing, Jiangsu Province, China. Malassezia is the dominant resident fungi in healthy individuals. ITS sequencing provides comprehensive information about fungal community in otomycosis and is helpful in evaluating the efficacy of antifungal agents.


Mental health problems in primary care: a research agenda.
The NAPCRG Task Force on Mental Health Problems was commissioned to explore critical research and policy issues in mental health and to develop a primary care research agenda for review and action by NAPCRG. This "White Paper" presents the key findings and recommendations of the Task Force. A comprehensive review of the primary care mental health literature, using MEDLINE searches with manual follow up, and personal communications with many active researchers in the field were performed by the authors; Task Force members participated in the editing and refinement of the White Paper in a series of email and face-to-face meetings. Although primary care researchers have made major contributions to our growing understanding of mental health problems as they exist in the "real world" of primary care, rapid changes in the U.S. health care environment threaten to undo the integration of mental and physical health that is at the heart of primary care. It will be necessary for the primary care leaders in this field to step forward to guide policy-makers, purchasers, and the public as primary care is reengineered for the next generation. Efforts to operationalize episode of care and comorbidity recording with EMR systems, particularly in cooperation with managed care corporations and/or primary care research networks, may represent the most effective strategy for promoting the integration of mental health services into primary care. The most promising area for research in the immediate future may be descriptive studies that capture and explore the clinical epidemiology of common mental health problems as they occur in routine practice.


Proteome and immunome of pathogenic Leptospira spp. revealed by 2DE and 2DE-immunoblotting with immune serum.
In this study, proteomes of two pathogenic Leptospira spp., namely L. interrogans, serogroup Icterohaemorrhagiae, serovar Copenhageni and L. borgpetersenii, serogroup Tarassovi, serovar Tarassovi, were revealed by using two dimensional gel electrophoresis (2DE)-based-proteomics. Bacterial cells were disrupted in a lysis buffer containing 30 mM Tris, 2 M thiourea, 7 M urea, 4% CHAPS, 2% IPG buffer pH 3-10 and protease inhibitors and then subjected to sonication in order to solubilize as much as possible the bacterial proteins. The 2DE-separated components of both Leptospira homogenates were blotted individually onto membranes and antigenic components (immunomes) were revealed by probing the blots with immune serum of a mouse readily immunized with the homogenate of L. interrogans, serogroup Icterohaemorrhagiae, serovar Copenhageni. The immunogenic proteins of the two pathogenic Leptospira spp. could be grouped into 10 groups. These are: 1) proteins involved in the bacterial transcription and translation including beta subunit transcription anti-termination protein of DNA polymerase III, elongation factors Tu and Ts, and tRNA (guanine-N1)-methyltransferase; 2) proteins functioning as enzymes for metabolisms and nutrient acquisition including acetyl-Co-A acetyltransferase, putative glutamine synthetase, glyceraldehyde-3-phospahte dehydrogenase, NifU-like protein, 3-oxoacyl-(acyl-carrier-protein) reductase, oxidoreductase, sphingomyelinase C precursor, spermidine synthase, beta subunit of succinyl-CoA synthetase, and succinate dehydrogenase iron-sulfur subunit; 3) proteins/enzymes necessary for energy and electron transfer, i.e. electron transfer flavoprotein, and proton-translocating transhydrogenase; 4) enzymes for degradation of misfolded proteins, i.e. ATP-dependent Clp protease; 5) molecular chaperone, i.e. 60 kDa chaperonin; 6) signal transduction system, i.e. response regulator; 7) protein involved in immune evasion in host, i.e. peroxiredoxin; 8) cell structure proteins including MreB (cytoskeletal) and flagellin/ periplasmic flagellin; 9) lipoproteins/outer membrane proteins: LipL32, LipL41, LipL45 and OmpL1; and 10) various hypothetical proteins. Many immunogenic proteins are common to both Leptospira spp. These proteins not only are the diagnostic targets but also have potential as candidates of a broad spectrum leptospirosis vaccine especially the surface exposed components which should be vulnerable to the host immune effector factors.


Prevalence of molar-incisor-hypomineralisation among children participating in the Dutch National Epidemiological Survey (2003).
This was to determine the prevalence of Molar-Incisor-Hypomineralisation (MIH) among children participating in the Dutch National Epidemiological Survey of 2003 and to compare the prevalence data with that found in the previous survey of 1999 when MIH was found in 9.7% of 11-year-old Dutch children. The survey took place in the same four cities as the previous survey in 1999. In 442 9-year-old children born in 1994, first permanent molars and all permanent incisors were examined for demarcated opacities, post-eruptive enamel breakdown, atypical restorations and extractions due to MIH. Children were considered as having MIH, when at least one molar was affected, with or without involvement of the incisors. Of the children examined 63 or 14.3% had at least one affected molar with hypomineralisation defects. Of those children with MIH only demarcated opacities were present in 35 (55.6%), while 13 (20.6 %) had at least one tooth with occlusal breakdown in addition to opacities, and in 15 (23.8%) atypical restorations were found. No teeth had been extracted due to MIH. Of the children with MIH there were 36 (57.1%) who had both molars and incisors affected. A significantly higher prevalence of MIH has been found in Dutch 9 year-old children in the last National Epidemiological Survey of 2003 as compared with to the Survey of 1999.


Sphingolipid content of human adipose tissue: relationship to adiponectin and insulin resistance.
Ceramides (Cer) are implicated in obesity-associated skeletal muscle and perhaps adipocyte insulin resistance. We examined whether the sphingolipid content of human subcutaneous adipose tissue and plasma varies by obesity and sex as well as the relationship between ceramide content and metabolic indices. Abdominal subcutaneous adipose biopsies were performed on 12 lean adults (males = 6), 12 obese adults (males = 6) for measurement of sphingolipid content and activity of the main ceramide metabolism enzymes. Blood was sampled for glucose, insulin (to calculate homeostasis model assessment-estimated insulin resistance (HOMA(IR))) adiponectin, and interleukin-6 (IL-6) concentrations. Compared to lean controls, total ceramide content (pg/adipocyte) was increased by 31% (P < 0.05) and 34% (P < 0.05) in obese females and males, respectively. In adipocytes from obese adults sphingosine, sphinganine, sphingosine-1-phosphate, C14-Cer, C16-Cer, and C24-Cer were all increased. C18:1-Cer was increased in obese males and C24:1-Cer in obese females. For women only, there was a negative correlation between C16-Cer ceramide and plasma adiponectin (r = -0.77, P = 0.003) and a positive correlation between total ceramide content and HOMA(IR) (r = 0.74, P = 0.006). For men only there were significant (at least P < 0.05), positive correlations between adipocyte Cer-containing saturated fatty acid and plasma IL-6 concentration. We conclude that the sexual dimorphism in adipose tissue behavior in humans extends to adipose tissue sphingolipid content its association with adiponectin, IL-6 and insulin resistance.


[The differential diagnosis of fatal outcomes in patient treatment with lidocaine].
A method for isolation, identification, and measurement of lidocaine is proposed for investigations of biological specimens. The presence of lidocaine is confirmed by common alkaloid reactions, chromatography in a thin layer of adsorbent, and color test. Lidocaine concentration is measured by extraction photoelectrocolorimetry. A formula is proposed, permitting a tentative assessment of the injected lidocaine dose. The threshold identification value is 0.2 mg%, threshold detection value 0.5 mg%.


Presenilin 1 Gene Mutation (M139V) in a German Family with Early-Onset Alzheimer's Disease: A Case Report.
This study describes a 44-year-old German male with early-onset Alzheimer's disease as a result of a M139V presenilin 1 mutation. The patient has at least seven affected family members, spanning at least four generations. We performed a complete demographic, genetic, neuropsychological, neuropsychiatric, neuroradiological, and neuropathological characterizations of this patient. The findings were compared with previous reports of patients with the same mutation. Demographic, neuropsychological, neuropsychiatric, neuroradiological, and neuropathological data from several affected members of the patient's family were also addressed. We describe similarities shared with other cases, including age at onset, rapid disease progression, severe deficits in arithmetic and visuo-constructive abilities with relative preservation of naming skills, and the presence of predominant frontal behavioral symptoms. Differences with respect to previously described cases, including the absence of positive neurological or radiological findings, psychotic symptoms, or a depressive disorder, are also identified and discussed. Heterogeneity in symptoms between affected patients from the same or from different families suggests that individual, genetic, or epigenetic factors most likely modulate the phenotype of patients carrying the M139V mutation.


Tailoring of locust bean gum and development of hydrogel beads for controlled oral delivery of glipizide.
In this study, carboxymethyl derivative of locust bean gum was prepared, characterized, and its gelling ability with different concentrations (1-5% w/v) of aluminum chloride (AlCl(3)) was utilized for the development of glipizide-loaded beads in a completely aqueous environment. The beads were spherical when observed under a scanning electron microscope. Increase in gelling ion concentration decreased the drug entrapment efficiency from 97.68% to 95.14%. The beads swelled more slowly in pH 1.2 KCl-HCl buffer and exhibited a slower drug release pattern than that observed in pH 7.4 phosphate buffer. Irrespective of the dissolution media, the drug release became slower at higher AlCl(3) concentration. The drug release in alkaline medium was found to be controlled by a combination of diffusion as well as polymer relaxation phenomena. Comparing the release profiles, it was observed that the beads treated with 5% AlCl(3) provided slower drug release up to 10 h in alkaline medium without any sign of disintegration and, thus, this formulation was selected for further studies. Fourier transform infrared (FTIR) spectroscopy indicated the stable nature of the drug in the beads. Differential scanning calorimetry and X-ray diffraction analysis showed that most of the drug remained in amorphous state in the beads. Stability study indicated no statistical significant difference in drug entrapment efficiency of the beads. In vivo activity of the beads was tested and a prolonged hypoglycemic effect was achieved. Hence, carboxymethyl locust bean beads could be a potential carrier for controlled oral delivery of glipizide.


Molecular epidemiology and genetic diversity of fluoroquinolone-resistant Escherichia coli isolates from patients with community-onset infections in 30 Chinese county hospitals.
The high frequency of fluoroquinolone resistance in Escherichia coli is a feature of clinical bacteriology in China, where the molecular epidemiology and genetic characteristics of this resistance in county hospitals remain unclear. A total of 590 nonduplicate E. coli isolates from 30 county hospitals located across seven Chinese regions were examined for plasmid-mediated quinolone resistance (PMQR) genes and mutations in quinolone resistance-determining regions (QRDRs). Multilocus sequence typing (MLST) and phylogenetic analysis of fluoroquinolone-resistant isolates were used to determine their genetic relatedness. The ciprofloxacin resistance rate of community-onset E. coli was 51.2%, and at least one PMQR gene was carried by 220 (37.3%) isolates. These included qnr (3.7%), aac(6')-Ib-cr (19.7%), qepA (14.4%), and oqxAB (3.8%). Two novel oqxB mutants were identified and named oqxB20 and oqxB29. From 60 sequence types (STs) isolated, 5 novel STs (ST4499 to ST4503) were identified. ST1193 (7.9%) was the second most abundant ST among fluoroquinolone-resistant isolates (ST131 was the most common, with 14.6%), and this is the first report of it in China. This is also the first report of ST2115 and ST3014 isolates from human samples. Ciprofloxacin-resistant E. coli isolates fell mainly into phylogroups B2 and D. The rates of fluoroquinolone resistance and the prevalence of PMQR genes in community-onset E. coli isolates from Chinese county hospitals were high. The wide-ranging molecular epidemiology of E. coli isolates from scattered locations across China indicates that fluoroquinolone resistance evolved from different sources.


Iron chelators: in vitro inhibitory effect on the liver stage of rodent and human malaria.
The activity of desferrioxamine (Desferal) and desferrithiocin (a newly developed oral iron chelator) was evaluated against the liver stage of Plasmodium yoelii and P. falciparum in the rodent and the human hepatocyte in vitro culture system. The two iron chelators were found to inhibit the liver schizogony of both the rodent and the human Plasmodium species at concentrations achievable in vivo. P. falciparum proved to be more sensitive (ic 95% below 20 micromol/l than P. yoelii (ic 95% 50-100 micromol/l). As assessed by electron microscopy, drug administration was associated with focal clarification of the cytoplasm thought to be reversible. As desferrioxamine and desferrithiocin are known to be equally active on the blood stage of rodent and human plasmodia, iron chelators are deserving of further investigation as potential alternative candidates to existing drugs for radical cure of malaria.


Membranous fat necrosis in mature cystic teratomas of the ovary.
We identified and documented the occurrence of membranous fat necrosis (MFN) in 217 mature cystic teratomas (MCTs) of the ovary. Cysts lined by an eosinophilic and scalloped membrane with pseudopapillary infoldings, the characteristic histologic features of MFN, were identified in 9 tumors. The membranes had the histochemical staining properties of ceroid, as evidenced by periodic acid-Schiff, sudan black, and long Ziehl Neelsen (ZN) positivity, diastase resistance, and autofluorescence. The causes and pathogenesis of MFN are enigmatic, but trauma, torsion, and ischemia are probable factors. MFN is a distinct entity in ovarian MCTs and heightened awareness will increase its histopathologic recognition.


Multiple target autoantigens on endothelial cells identified in juvenile dermatomyositis using proteomics.
Although generally classified within the group of inflammatory myopathies, JDM displays many pathological features of vasculitis. Previous work has shown that AECA are abundant in other forms of vasculitis. We therefore investigated whether such antibodies might also be detected in JDM. We screened plasma from children with JDM for the presence of AECA by western blotting and 2D gel electrophoresis (2DE) using proteins extracted from human aortic endothelial cells as the substrate. We performed mass spectrometry to identify candidate antigens from 2DE gels and used ELISA to confirm the presence of specific antibodies. We identified 22 candidate target autoantigens for AECA probed with JDM plasma. Interestingly, 17 of these 22 target antigens were proteins associated with antigen processing and protein trafficking. ELISA confirmed the presence of antibodies to heat shock cognate 71 kDa protein in JDM plasma, particularly in children with active, untreated disease. Children with JDM express antibodies to autoantigens in endothelial cells. The clinical and pathological significance of such autoantibodies require further investigation.


Multi-compartment scaffold fabricated via 3D-printing as in vitro co-culture osteogenic model.
The development of in vitro 3D models to get insights into the mechanisms of bone regeneration could accelerate the translation of experimental findings to the clinic, reducing costs and duration of experiments. This work explores the design and manufacturing of multi-compartments structures in poly(ε-caprolactone) (PCL) 3D-printed by Fused Filament Fabrication technique. The construct was designed with interconnected stalls to host stem cells and endothelial cells. Cells were encapsulated within an optimised gellan gum (GG)-based hydrogel matrix, crosslinked using strontium (Sr2+) ions to exploit its bioactivity and finally, assembled within compartments with different sizes. Calcium (Ca2+)-crosslinked gels were also used as control for comparison of Sr2+ osteogenic effect. The results obtained demonstrated that Sr2+ ions were successfully diffused within the hydrogel matrix and increased the hydrogel matrix strength properties under compressive load. The in vitro co-culture of human-TERT mesenchymal stem cells (TERT- hMSCs) and human umbilical vein endothelial cells (HUVECs), encapsulated within Sr2+ ions containing GG-hydrogels and inter-connected by compartmentalised scaffolds under osteogenic conditions, enhanced cell viability and supported osteogenesis, with a significant increase of alkaline phosphatase activity, osteopontin and osteocalcin respect with the Ca2+-crosslinked GG-PCL scaffolds. These outcomes demonstrate that the design and manufacturing of compartmentalised co-culture of TERT-hMSCs and HUVEC populations enables an effective system to study and promote osteogenesis.


Ejaculatory disorders and lower urinary tract symptoms.
A growing body of literature supports the observed association between lower urinary tract symptoms and sexual dysfunction. The causal relationship between these two conditions has not been determined. Ejaculatory function is an important aspect of sexual functioning and recent studies have shown a high prevalence of this ejaculatory dysfunction in men with lower urinary tract symptoms. Furthermore, the degree of bother associated with ejaculatory dysfunction is quite high, making it an important problem for patients. Thus, health care providers should have a heightened sense of awareness for the presence of ejaculatory dysfunction and appropriate patient counseling should be undertaken before initiation of specific treatments for lower urinary tract symptoms.


Predictive value of serum sialic Acid in type-2 diabetes mellitus and its complication (nephropathy).
Sialic acid levels are increased in type-2 diabetes mellitus and its estimation helps in predicting the occurrence of microvascular complication such as diabetic nephropathy. The present study compared the levels of sialic acid, glycated haemoglobin, serum creatinine and urine microalbumin: in type-2 diabetics without any complications; in type-2 diabetics with nephropathy; and in age and sex matched healthy individual (controls). The study observed an increased level of sialic acid in type-2 diabetics without any complications and type-2 diabetics with nephropathy. Serum sialic acid levels in type-2 diabetics without any complications was 64.44 ± 3.93 mg/dl, in type-2 diabetics with nephropathy was 73.88 ± 4.41 mg/dl, and in controls it was 53.16 ± 3.40 mg/dl. Urine sialic acid levels in type-2 diabetics without any complications was 6.62 ± 0.70 mg/dl, in type-2 diabetics with nephropathy was 8.46 ± 0.97 mg/dl, and in controls it was 4.44 ± 0.62 mg/dl. Correlation of sialic acid levels with glycated haemoglobin and urine microalbumin was statistically significant but with serum creatinine was not statistically significant. Sialic acid is an important component of vascular cell membrane. Their increased levels indicate extensive vascular damage in type-2 DM. Therefore, estimation of sialic acid levels help in early prediction and prevention of microvascular complications occurring due to diabetics, thereby decreasing the mortality and morbidity in them.


High-resolution MRI of the ulnar and radial collateral ligaments of the wrist.
Background Accurate diagnosis of injuries to the collateral ligaments of the wrist is technically challenging on MRI. Purpose To investigate usefulness of high-resolution two-dimensional (2D) and isotropic three-dimensional (3D) magnetic resonance imaging (MRI) for identifying and classifying the morphology of the ulnar and radial collateral ligaments (UCL and RCL) of the wrist. Material and Methods Thirty-seven participants were evaluated using 3T coronal 2D and isotropic 3D images by two radiologists independently. The UCL was classified into four types: 1a, narrow attachment to the tip of the ulnar styloid (Tip); 1b, broad attachment to the Tip; 2a, narrow attachment to the medial base of the ulnar styloid (Base); and 2b, broad attachment to the Base. The RCL was also classified into four types: 1a, separate radioscaphoid and scaphotrapezial ligaments (RS + ST) with narrow scaphoid attachment; 1b, RS + ST with broad scaphoid attachment; 2a, continuous radio-scapho-trapezial ligaments (RST) with narrow scaphoid attachment; and 2b, RST with broad scaphoid attachment. The inter-observer reliability of these classifications was calculated. Results Type 1a was the most common of both collateral ligaments. Of UCL classifications, 31.4% were revised after additional review of multiplanar reconstruction (MPR) images from isotropic data. The inter-observer reliability of UCL classification was substantial (k = 0.62) without MPR, and almost perfect (k = 0.84) with MPR. The inter-observer reliability of RCL classification was almost perfect (k = 0.89). Anatomic delineation between the two sequences was not statistically different. Conclusion The UCL and RCL were each identified on high-resolution 2D and isotropic 3D MRI equally well. MPR allows accurate identification of the UCL attachment to the ulnar styloid.


A FEM Free Vibration Analysis of Variable Stiffness Composite Plates through Hierarchical Modeling.
Variable Angle Tow (VAT) laminates offer a promising alternative to classical straight-fiber composites in terms of design and performance. However, analyzing these structures can be more complex due to the introduction of new design variables. Carrera's unified formulation (CUF) has been successful in previous works for buckling, vibrational, and stress analysis of VAT plates. Typically, one-dimensional (1D) and two-dimensional (2D) CUF models are used, with a linear law describing the fiber orientation variation in the main plane of the structure. The objective of this article is to expand the CUF 2D plate finite elements family to perform free vibration analysis of composite laminated plate structures with curvilinear fibers. The primary contribution is the application of Reissner's mixed variational theorem (RMVT) to a CUF finite element model. The principle of virtual displacements (PVD) and RMVT are both used as variational statements for the study of monolayer and multilayer VAT plate dynamic behavior. The proposed approach is compared to Abaqus three-dimensional (3D) reference solutions, classical theories and literature results to investigate the effectiveness of the developed models. The results demonstrate that mixed theories provide the best approximation of the reference solution in all cases.


Variant Bernard-Soulier syndrome type bolzano. A congenital bleeding disorder due to a structural and functional abnormality of the platelet glycoprotein Ib-IX complex.
We have studied a patient with a congenital bleeding disorder and phenotypic manifestations typical of Bernard-Soulier syndrome, including giant platelets with absent ristocetin-induced von Willebrand factor binding. Two monoclonal antibodies reacting with distinct epitopes in the amino-terminal domain of the alpha-chain of glycoprotein (GP) Ib were used to estimate the number of GP Ib molecules on the platelet membrane. In the patient, binding of one antibody (LJ-Ib10) was approximately 50% of normal, while binding of the other (LJ-Ib1) was absent. Binding of both antibodies was reduced to approximately 50% of normal in the mother and one sister of the propositus, and their platelets exhibited approximately 70% of normal von Willebrand factor binding. Immunoblotting studies confirmed the presence of GP Ib alpha, as well as GP IX, in patient platelets. Antibody LJ-Ib10, but not LJ-Ib1, could immunoprecipitate the patient's GP Ib alpha from surface-labeled proteins. Thus, platelets from the propositus contained a structurally and functionally altered GP Ib-IX complex lacking a specific antibody epitope and the ability to bind von Willebrand factor. In contrast, the binding of human alpha-thrombin to the patient's platelets was normal, and three classes of binding sites with high, intermediate, and low affinity could be detected. These studies define a distinct variant form of Bernard-Soulier syndrome and provide evidence, based on a naturally occurring mutant molecule, that the amino-terminal region of GP Ib alpha contains a von Willebrand factor-binding domain distinct from the high affinity thrombin-binding site. Use of different monoclonal antibodies with distinct epitope specificities appears to be essential for a correct identification of variant Bernard-Soulier syndrome.


In Vitro Testing of an Implantable Wireless Telemetry System for Long-Term Electromyography Recordings in Large Animals.
Multichannel bio-signal recording in undisturbed in vivo conditions is a frequent demand in experimental work for development of methodology and associated equipment for functional electrical stimulation (FES) application, limb prosthesis, and diagnostic tools in contemporary rehabilitation efforts. Intramuscular electromyogram (EMG) recordings can provide comprehensive insight in complex interactions of agonistic and antagonistic muscles during movement tasks and in contrast act as reliable control signals for both neuroprosthesis and mechanical prosthesis. We fabricated a fully implantable device, which is capable of recording electromyography signals from inside a body and transmit these signals wirelessly to an external receiver. The developed analog front end uses only two electrodes per channel, provides a gain of 60 dB, and incorporates a band pass filter with lower cut-off frequency of 4 Hz and upper cut-off frequency of 480 Hz. The bidirectional wireless data link, which operates in the 2.4 GHz Industrial, Scientific and Medical band, is designed for transmission distances of 10 m using an application data rate of 1 kSps for each of the two channels. Performed in vitro tests with the devices coated in epoxy resin and inserted into a phantom with tissue-equivalent characteristics confirmed the functionality of our concept and the measurement results are consistent with those from preceding simulations.


Search for the Decays B_{s}^{0}→τ^{+}τ^{-} and B^{0}→τ^{+}τ^{-}.
A search for the rare decays B_{s}^{0}→τ^{+}τ^{-} and B^{0}→τ^{+}τ^{-} is performed using proton-proton collision data collected with the LHCb detector. The data sample corresponds to an integrated luminosity of 3 fb^{-1} collected in 2011 and 2012. The τ leptons are reconstructed through the decay τ^{-}→π^{-}π^{+}π^{-}ν_{τ}. Assuming no contribution from B^{0}→τ^{+}τ^{-} decays, an upper limit is set on the branching fraction B(B_{s}^{0}→τ^{+}τ^{-})<6.8×10^{-3} at the 95% confidence level. If instead no contribution from B_{s}^{0}→τ^{+}τ^{-} decays is assumed, the limit is B(B^{0}→τ^{+}τ^{-})<2.1×10^{-3} at the 95% confidence level. These results correspond to the first direct limit on B(B_{s}^{0}→τ^{+}τ^{-}) and the world's best limit on B(B^{0}→τ^{+}τ^{-}).


A persistent giant Eustachian valve: functional tricuspid atresia in a newborn.
Persistent right valve of the systemic venous sinus is a rare anomaly with anatomical variations. This anomaly may present as an obstructive structure that can inhibit the antegrade flow through the tricuspid valve. We report on a 4-day-old neonate who presented with pronounced peripheral and central cyanosis. Echocardiographic examination showed a giant Eustachian valve moving towards the tricuspid valve during late systole and leading to complete obstruction of the inflow. Blood flow was redirected through the persistent foramen ovale, producing a right-to-left shunt.


Performance of a new guideline for telephone triage in out-of-hours services in Belgium: A pilot study using simulated patients.
Patients in Belgium needing out-of-hours care have two options: the emergency department or the general practitioner on call often organised in a general practitioner cooperative. Currently, there is no triage system in Belgium so patients do not know where to go. Our primary objective was to examine the ability of a newly developed telephone guideline, called 1733, to adequately estimate the urgency of health problems presented by simulated patients. Ten clinical vignettes were presented to 12 operators in a simulated phone call. The operators had to assign a protocol, urgency level and resource to dispatch (ambulance, general practitioner house visit, etc.) to each case. A total of 120 phone calls were analysed. The operators chose the right protocol in 69% and the correct urgency level in 35% of the cases. The proportion of under- and over-triage was 26% and 39%, respectively. There was important variation in between the operators. The sensitivity for detecting highly urgent cases was 0.42, the specificity 0.92. Using the new Belgian 1733 guideline for telephone triage, operators mostly chose the appropriate protocol but only chose the correct urgency in one out of three cases. In this phase of development, the studied telephone guideline is not ready for implementation.


Minimally invasive endoscopic removal of a herniated nucleus pulposus that had migrated to the S1 nerve root foramen.
In this report, we described an adult case with a lumbar herniated nucleus pulposus that had migrated to the S1 nerve root foramen from L5-S1 disc space. Endoscopically, the migrated mass was successfully removed after laminectomy at the S1 with a small skin incision of 20 mm in length. Unlike the other levels, the intraforaminally migrated mass along the S1 root can be excised without any removal of the facet joints; therefore, additional spinal fusion is not necessary. Thus, an S1 foraminal migrated mass can be a good surgical candidate for minimally invasive endoscopic surgery.


Optimization of heme precursors for the expression of human cytochrome P450 2A13 and its co-expression with oxidoreductase in baculovirus/sf9 system.
Human cytochrome P450 2A13 (CYP2A13), mainly expressed in respiratory tract, is active towards numerous toxicants. To establish the metabolism in vitro, we expressed CYP2A13 and NADPH-CYP450 oxidoreductase (POR) in a baculovirus/sf9 system. Due to the deficiency of sf9 cells in heme incorporation, we investigated the effects of different heme precursors on the expression of CYP2A13, POR and their co-expression. The present results showed that both CYP2A13 and POR were presented the highest expression levels or activity with 0.2 mM δ-aminolaevulinic acid (5-ALA), 0.02 mM Fe(3+) and 0.5-1.0 μg/ml hemin. The combination of 0.2 mM 5-ALA and 0.02 mM Fe(3+) significantly improved CYP2A13 expression and content compared with heme precursors alone, so was POR activity. A multiplicity of infection (MOI) value of 5 pfu/cell for CYP2A13 baculovirus particles induced very high CYP2A13 expression. When co-infected with different POR MOI values, a viral ratio of 5 : 2 was associated with the highest CYP2A13 activity, whereas POR activity dose dependently increased with POR MOI. Furthermore, the expressed CYP2A13 in the optimized conduction could eliminate its substrate aflatoxin B1 at a significantly higher than those in other condition (P < 0.01). Our results provide an efficient approach for expressing functionally characterized, highly active and homogeneous CYP2A13 proteins.


Flexible modelling of vaccine effect in self-controlled case series models.
The self-controlled case series (SCCS) method, commonly used to investigate the safety of vaccines, requires information on cases only and automatically controls all age-independent multiplicative confounders, while allowing for an age-dependent baseline incidence. Currently, the SCCS method represents the time-varying exposures using step functions with pre-determined cut points. A less prescriptive approach may be beneficial when the shape of the relative risk function associated with exposure is not known a priori, especially when exposure effects can be long-lasting. We therefore propose to model exposure effects using flexible smooth functions. Specifically, we used a linear combination of cubic M-splines which, in addition to giving plausible shapes, avoids the integral in the log-likelihood function of the SCCS model. The methods, though developed specifically for vaccines, are applicable more widely. Simulations showed that the new approach generally performs better than the step function method. We applied the new method to two data sets, on febrile convulsion and exposure to MMR vaccine, and on fractures and thiazolidinedione use.


Effects of a weight management program delivered by social media on weight and metabolic syndrome risk factors in overweight and obese adults: A randomised controlled trial.
The aim of this project was to evaluate the effectiveness of using social media to augment the delivery of, and provide support for, a weight management program delivered to overweight and obese individuals during a twenty four week intervention. Participants randomly divided into either one of two intervention groups or a control group. The two intervention groups were instructed to follow identical weight-management program. One group received the program within a Facebook group, along with a support network with the group, and the other intervention group received the same program in a booklet. The control group was given standard care. Participants' weight and other metabolic syndrome risk factors were measured at baseline and at weeks 6, 12, 18 and 24. The Facebook Group reported a 4.8% reduction in initial weight, significant compared to the CG only (p = 0.01), as well as numerically greater improvements in body mass index, waist circumference, fat mass, lean mass, and energy intake compared to the Pamphlet Group and the Control Group. These results demonstrate the potential of social media to assist overweight and obese individuals with respect to dietary and physical activity modifications for weight management, and justify further research into the inclusion of social media in clinical weight management programs. It is anticipated that social media will provide an invaluable resource for health professionals, as a low maintenance vehicle for communicating with patients, as well as a source of social support and information sharing for individuals undergoing lifestyle modifications.


Structural Basis for Human Receptor Recognition by SARS-CoV-2 Omicron Variant BA.1.
The highly contagious and fast-spreading omicron variant of SARS-CoV-2 infects the respiratory tracts efficiently. The receptor-binding domain (RBD) of the omicron spike protein recognizes human angiotensin-converting enzyme 2 (ACE2) as its receptor and plays a critical role in the tissue tropism of SARS-CoV-2. Here, we showed that the omicron RBD (strain BA.1) binds to ACE2 more strongly than does the prototypic RBD from the original Wuhan strain. We also measured how individual omicron mutations affect ACE2 binding. We further determined the crystal structure of the omicron RBD (engineered to facilitate crystallization) complexed with ACE2 at 2.6 Å. The structure shows that omicron mutations caused significant structural rearrangements of two mutational hot spots at the RBD/ACE2 interface, elucidating how each omicron mutation affects ACE2 binding. The enhanced ACE2 binding by the omicron RBD may facilitate the omicron variant's infection of the respiratory tracts where ACE2 expression level is low. Our study provides insights into the receptor recognition and tissue tropism of the omicron variant. IMPORTANCE Despite the scarcity of the SARS-CoV-2 receptor-human angiotensin-converting enzyme 2 (ACE2)-in the respiratory tract, the omicron variant efficiently infects the respiratory tract, causing rapid and widespread infections of COVID-19. The omicron variant contains extensive mutations in the receptor-binding domain (RBD) of its spike protein that recognizes human ACE2. Here, using a combination of biochemical and X-ray crystallographic approaches, we showed that the omicron RBD binds to ACE2 with enhanced affinity and also elucidated the role of each of the omicron mutations in ACE2 binding. The enhanced ACE2 binding by the omicron RBD may contribute to the omicron variant's new viral tropism in the respiratory tract despite the low level of ACE2 expression in the tissue. These findings help us to understand tissue tropism of the omicron variant and shed light on the molecular evolution of SARS-CoV-2.


[Effects of Huaiqihuang granules on immune function in children with severe Mycoplasma pneumoniae pneumonia].
To observe the effects of Huaiqihuang granules on the immune function in children with severe Mycoplasma pneumoniae pneumonia. Pediatric inpatients with severe Mycoplasma pneumoniae pneumonia were randomly divided into Huaiqihuang granule treatment group (n=51) and conventional treatment group (n=47). The Huaiqihuang granule treatment group was orally administered Huaiqihuang granules in addition to the conventional treatment, while the conventional treatment group received conventional treatment only. Levels of serum IgA, IgG, and IgM, percentages of CD4+ and CD8+ T lymphocyte subsets, and CD4+/CD8+ ratio were examined in the two groups. The incidence rate of respiratory tract re-infection within three months following treatment was compared between the two groups. The levels of serum IgA, IgG, and IgM, the percentage of CD4+ T lymphocytes, and the CD4+/CD8+ ratio were significantly higher in the Huaiqihuang granule treatment group than in the conventional treatment group three months after treatment (P<0.05). In contrast, the percentage of CD8+ T lymphocytes was significantly lower in the Huaiqihuang granule treatment group than in the conventional treatment group (P<0.05). In addition, the incidence rate of respiratory tract re-infection within three months following treatment was significantly lower in the Huaiqihuang granule treatment group than in the conventional treatment group (P<0.05). Huaiqihuang granules can regulate immune functions and reduce the incidence of short-term respiratory tract re-infection in children with severe Mycoplasma pneumoniae pneumonia.


Expression of p16, p53 and Ki-67 proteins in the progression of epithelial dysplasia of the oral cavity.
The overexpression of the protein products of genes associated with the cell cycle tumour protein53 (p53), cyclin-dependent kinase inhibitor 2A (p16) and antigen identified by monoclonal antibody Ki-67 (Ki-67) is apparently of great significance. This study evaluated the immunohistochemical expression of these proteins in precancerous lesions and in carcinoma of the oral cavity. The nuclear expression of p53 and Ki-67 and nuclear and/or cytoplasmic expression of p16 protein was examined in 54 biopsy specimens from the oral cavity obtained over a period of 3 years. The samples included 18 cases of normal/hyperplastic mucosa, 25 cases of dysplasia and 11 cases of invasive squamous cell carcinoma. The specimens were grouped into three categories: 1 = no or mild dysplasia, 2 = moderate or severe dysplasia, and 3 = invasive carcinoma. p16 was negative in all the group 1 specimens, while both p53 and Ki-67, when present, were limited to the cells of the basal layer. In the group 2 specimens, the number of p16-, p53-, and Ki-67-positive cells increased as the grade of dysplasia progressed. In group 3 (invasive carcinomas), p53 and p16 expression occurred respectively in 81.8% and 54.5% of cases, while Ki-67 was elevated in all the cases. The expression of the cell-cycle proteins p16 and p53 in the dysplastic epithelium, in association with Ki-67, may represent significant markers to recognize evolution of precancerous disease in the oral cavity and to improve identification of the degree of dysplasia.


A Preliminary Analysis of Mastery Criterion Level: Effects on Response Maintenance.
Educators use a mastery criterion to evaluate skill acquisition programming for children with autism and other developmental disabilities; however, to the best of our knowledge, there has been no research evaluating how the mastery criterion level of accuracy affects the maintenance of those responses. This study investigated the effects of 3 skill acquisition mastery criterion levels (50%, 80%, and 90% accuracy) on response maintenance. Following mastery of a set of skills, maintenance was evaluated once a week for 3 to 4 weeks. Three elementary school-age children diagnosed with autism participated. Overall, the outcomes suggested that higher mastery criterion levels (90% correct) produced higher levels of maintenance responding. Additional research in this area is needed to clarify how different parameters of mastery criterion affect the generality of skills.


Outcome of critically ill patients with hematological malignancies.
The prognosis for patients with hematological malignancies (HMs) admitted to the intensive care unit (ICU) is poor. The objective of this study was to evaluate the clinical characteristics and hospital outcomes of critically ill patients with HMs admitted to an oncological ICU. This is a prospective, observational cohort study. A total of 102 patients with HMs admitted to ICU from January 2008 to April 2011 were included. Univariate and multivariate logistic regressions were used to identify factors associated with hospital mortality. During the study period, 3,776 patients with HM were admitted to the Department of Hematology of the Instituto Nacional de Cancerología located in Mexico City, Mexico. After being evaluated by the intensivist, 102 (2.68 %) patients were admitted to the ICU. The ICU mortality rates for patients who had two or less organ system failures and for those with three or more organ system dysfunctions were 20 % (5/25) and 70.1 % (54/77), respectively (P < 0.0001). A multivariate analysis identified independent prognostic factors of in-hospital death as neutropenia at the time of ICU admission (odds ratio (OR), 4.24; 95 % confidence interval (CI), 1.36-13.19, P = 0.012), the need for vasopressors (OR, 4.49; 95 % CI, 1.07-18.79, P = 0.040), need for invasive mechanical ventilation (OR, 4.49; 95 % CI, 1.07-18.79, P = 0.040), and serum creatinine >106 μmol/L (OR, 3.21; 95 % CI, 1.05-9.85, P = 0.041). The ICU and hospital mortality rates were 46.1 and 57.8 %, respectively. The independent prognostic factors of in-hospital death were the need for invasive mechanical ventilation, the need for vasopressors, serum creatinine >106 μmol/L, and neutropenia at the time of ICU admission.


Au(144-x)Cu(x)(SC6H13)60 nanomolecules: effect of Cu incorporation on composition and plasmon-like peak emergence in optical spectra.
Au144-xCux(SR)60 alloy nanomolecules were synthesized and characterized by using ESI-MS to atomic precision. A maximum of 23 copper atoms replace the gold atoms. When the number of copper atoms is higher than eight, a surface plasmon-like peak appears at ∼520 nm. Based on the fundamental elemental properties of Au and Cu, we predict a mixed atomic ordering and incorporation of Cu atoms into the Au12 and Au42 shells of the proposed icosahedral structure model of the 144-atom nanomolecule.


[Synthesis and anti-tumor activity of ginsenoside Rh_2 caprylic acid monoester].
Ginsenoside Rh_2,firstly isolated from red ginseng,is protopanaxadiol type of steroidal saponin. Rh_2 possessed variety of activities,but bioavailability of oral administration Rh_2 was extremely low due to poor absorption. Moreover,ginsenoside Rh_2 exhibited toxicity on human normal cells. Therefore,to improve stronger anti-tumor activity and attenuate toxicity,it was essential to design and optimize chemical structure of ginsenoside Rh_2. Through n-octanoylchloride modifications,a novel ester derivative of ginsenoside Rh_2 named caprylic acid monoester of Rh_2( C-Rh_2) was designed and synthesized. Structure of novel ginsenoside derivative was identified by1 D and 2 D NMR,as well as ESI-MS analyses. Anti-tumor effect of C-Rh_2 was tested on H22 tumor bearing mice. C-Rh_2 displayed certain anti-tumor activities and exhibited less toxicity than Rh_2. In the present study,C-Rh_2 as ester form of ginsenoside Rh_2 showed better anti-tumor activity and less toxicity,but the specific mechanism needs further investigation.


Helicobacter pylori, non-steroidal anti-inflammatory drugs and smoking in risk pattern of gastroduodenal ulcers.
Helicobacter pylori, NSAID and cigarette smoking are major risk factors for gastroduodenal ulcers. However, the results of studies on the interaction between these factors on ulcerogenesis are controversial. This study was designed to examine the association between gastroduodenal ulcers and H. pylori infection, NSAID use, smoking and age. 5967 dyspeptic patients underwent 13C-urea breath test (UBT) and upper endoscopy, while age and dyspeptic symptoms were reported. Out of 5967 patients, 31.8% were ulcerated; 9.2% had gastric, 17.2% duodenal and 5.4% both gastric and duodenal ulcers. H. pylori was found in 72.5% of gastric ulcer patients, in 83.6% of duodenal ulcer patients, in 76.9% of gastroduodenal ulcer patients and in 64.8% of dyspeptic patients. The gastric, duodenal and gastroduodenal ulcers were related to H. pylori significantly and the respective ORs were: 1.44, 2.77 and 1.81. NSAID alone was used by 6.2%-12.7% of ulcer patients, tending to raise only the risk of gastric ulcer but reducing that of duodenal and gastroduodenal ulcers. The H. pylori prevalence was significantly higher in smokers (76%) than in non-smokers (67%) and the ulcer risk was also significantly higher in smokers than in non-smokers. About 20% of ulcers were 'idiopathic', i.e. without NSAID and H. pylori and the ratio of these ulcers to all ulcers significantly increased during the 5 years of the study. Based on multivariable logistic regression analysis we conclude that: 1) H. pylori infection, NSAID use, smoking and age play major roles in the pathogenesis of peptic ulcerations; 2) there is a negative interaction between H. pylori and NSAID on duodenal ulcers, suggesting that H. pylori reduces the development of these ulcers in NSAID users, and 3) about 20% of peptic ulcers in the Polish population are unrelated to H. pylori and NSAID use (idiopathic ulcers).


Molecular analysis of Turkish Gaucher disease patients: identification of novel mutations in glucocerebrosidase (GBA) gene.
Gaucher disease (GD) is the most frequent lysosomal glycolipid storage disorder due to autosomal recessive deficiency of acid beta-glucosidase and is characterized by the accumulation of glucocerebroside. In this work we carried out molecular analysis of the glucocerebrosidase gene (GBA) in 57 unrelated patients and the alleleic frequencies of gene mutations in Turkish patients are reported. The most prevalent are L444P and N370S accounting for 42% and 30% in our patients. We identified three novel genetic alterations: two missense changes S356F, L296V that are associated with the severe phenotype of type 1 GD. 303-305delCAC was identified in a homozygous state in one patient type 1 or type 3.


Analysis of the correlations between the extracranial internal carotid artery and extracranial vertebral artery and mild cognitive impairment.
Vascular tortuosity is a prevalent morphological change that frequently occurs in arteries across different parts of the body. To analyze the relationship between the tortuosities of the extracranial internal carotid artery (EICA) and extracranial vertebral artery (EVA) with mild cognitive impairment. The tortuosity index (TI), vascular deviation degree, tortuosity degree, and angle number of the EICA and EVA were retrospectively analyzed and calculated in 160 patients who underwent computed tomography angiography (CTA) in this study's department, and the Montreal cognitive assessment was adopted to evaluate the cognitive function of the patients. The differences in age, gender, arterial hypertension (AH), and diabetes mellitus (DM) between the normal group and the mild cognitive impairment group were statistically significant (p< 0.01). The TI was negatively correlated with the score of cognitive function. The tortuosities of the EICA and EVA were correlated with mild cognitive impairment (p< 0.05). The reduction in visual-spatial ability was correlated with the right EICA tortuosity, and the reduction in memory was correlated with the EVA tortuosity. Age, gender, HP, DM, and coronary heart disease (CHD) were potential risk factors for carotid tortuosity (p< 0.05). There was a significant correlation observed between the TIs of both the EICA and EVA and the presence of mild cognitive impairment. Advanced age, female, HP, DM, and CHD were independent risk factors for EICA and EVA tortuosities.


Breaking the radiation damage limit with Cryo-SAXS.
Small angle x-ray scattering (SAXS) is a versatile and widely used technique for obtaining low-resolution structures of macromolecules and complexes. SAXS experiments measure molecules in solution, without the need for labeling or crystallization. However, radiation damage currently limits the application of SAXS to molecules that can be produced in microgram quantities; for typical proteins, 10-20 μL of solution at 1 mg/mL is required to accumulate adequate signal before irreversible x-ray damage is observed. Here, we show that cryocooled proteins and nucleic acids can withstand doses at least two orders of magnitude larger than room temperature samples. We demonstrate accurate T = 100 K particle envelope reconstructions from sample volumes as small as 15 nL, a factor of 1000 smaller than in current practice. Cryo-SAXS will thus enable structure determination of difficult-to-express proteins and biologically important, highly radiation-sensitive proteins including light-activated switches and metalloenzymes.


Could some geriatric characteristics hinder the prescription of anticoagulants in atrial fibrillation in the elderly?
Several studies have reported underprescription of anticoagulants in atrial fibrillation (AF). We conducted an observational study on 142 out of a total of 995 consecutive ≥75 years old patients presenting AF (14%) when admitted in an emergency unit of a general hospital, in search of geriatric characteristics that might be associated with the underprescription of anticoagulation therapy (mostly antivitamin K at the time of the study). The following data was collected from patients presenting AF: medical history including treatment and comorbidities, CHADS2 score, ISAR scale (frailty), Lawton's scale (ADL), GDS scale (mood status), MUST (nutrition), and blood analysis (INR, kidney function, and albumin). Among those patients for who anticoagulation treatment was recommended (73%), only 61% were treated with it. In the group with anticoagulation therapy, the following characteristics were observed more often than in the group without such therapy: a recent (≤6 months) hospitalization and medical treatment including digoxin or based on >3 different drugs. Neither the value of the CHADS2 score, nor the geriatric characteristics could be correlated with the presence or the absence of an anticoagulation therapy. More research is thus required to identify and clarify the relative importance of patient-, physician-, and health care system-related hurdles for the prescription of oral anticoagulation therapy in older patients with AF.


The role of angiogenesis, laminin and CD44 expression in metastatic behavior of early-stage low-grade invasive breast carcinomas.
To investigate the role of tumor angiogenesis, laminin and CD44 expression in metastatic potential of breast cancers, 35 early-stage (T1) and/or low-grade (grade 1) invasive breast carcinomas including 18 metastasizing and 17 non-metastasizing cases were analyzed in the present study. Angiogenesis was assessed by a stereologic method after immunohistochemical staining of vascular endothelium for factor VIII. The quantification of the tumor vascularization was based on the vascular surface density (VSD) and the microvessel number (NVES). The expressions of laminin and CD44 were evaluated by scoring the intensity and distribution of the immunostaining. The assessment of NVES and VSD resulted in a statistically significant difference between the two groups (P < 0.05, independent-samples t-test). In the breast cancers with metastatic spread, NVES was found to be 16.0+/-2.9 mm(-2) whereas it was 8.1+/-0.7 mm(-2) in the metastasizing group. VSD was found to be 59.0+/-12.6 mm(-1) in the metastasizing group and was significantly lower in the non-metastasizing group (33.8+/-2.6 mm[-1]). Immunohistochemistry exhibited strongly positive staining for CD44 in 22% of the breast cancers with metastasis, while 65% of the non-metastasizing cases were found to be negative. The statistical analysis also resulted in a significant difference (P = 0.034, chi2 test). However, the immunohistochemical staining for laminin did not yield any significant difference (P = 0.347, chi2 test). Approximately half of the cases being either metastasizing or non-metastasizing stained weakly positive for laminin. We concluded that angiogenesis and CD44 expression in breast cancers correlated significantly with lymph node or distant metastasis. However, the immunodetection of laminin expression in our study did not help to evaluate its role in the metastatic potential of breast cancers. We concluded that vascular parameters, such as an increase in microvessel number, and CD44 expression might be useful prognostic indicators of metastasis in breast cancer.


[Indications and long-term outcomes for solid organ transplant. Quality of life in solid organ transplant recipients].
Organ transplant constitutes one of the most encouraging advances in the history of the medicine. The organ transplants that were a distant challenge in the seventies currently are a routine procedure in the medical practice that has contributed to extending survival and quality of life in the general population. Spain has reached the highest rate for donation and transplants per one million inhabitants worldwide, this extraordinary health care work being a combined achievement of Spanish Health Care System. The objective of this article is to review the indications of solid organ transplants and their long-term outcomes, evaluating the impact on the health-related quality of life in solid organ transplant recipients.


Insight from Frogs: Sonic Hedgehog Gene Expression and a Re-evaluation of the Vertebrate Odontogenic Band.
While the identification of conserved processes across multiple taxa leads to an understanding of fundamental developmental mechanisms, the ways in which different animals fail to conform to common developmental processes can elucidate how evolution modifies development to result in the vast array of morphologies seen today-the developmental mechanisms that lead to anatomical variation. Odontogenesis-how teeth are initiated and formed-is well suited to the examination of both developmental conservation and phenotypic diversity. We suggest here that the study of early tooth development, the period of odontogenic band development, reveals departures from conserved mechanisms that question the role of players in the developmental process. In the earliest stages of odontogenesis, Sonic hedgehog (Shh) gene expression is interpreted as critical evidence of tooth initiation prior to any histological indication. However, a detailed examination of studies of tooth development across a wide range of taxa reveals that several vertebrate species fail to conform to the expectations of the Shh Consensus Model, calling for a reconsideration of the assumed causality of epithelial Shh in tooth initiation. We present new Shh gene expression data for an amphibian, the frog Silurana (Xenopus) tropicalis. In these animals, craniofacial and odontogenic developmental processes are more disjunct, and thereby provide a natural test of the hypothesis that Shh is immediately required for subsequent tooth development. Our results suggest that Shh expression may actually be related to the formation of the mouth rather than a required precursor to subsequent tooth formation. Anat Rec, 299:1099-1109, 2016. © 2016 Wiley Periodicals, Inc.