BRD4S interacts with viral E2 protein to limit human papillomavirus late transcription.
The E2 protein encoded by human papillomaviruses (HPV) is a sequence-specific DNA-binding protein that recruits viral and cellular proteins. Bromodomain-containing protein 4 (BRD4) is a highly conserved interactor for E2 proteins that has been linked to E2's functions as transcription modulator, activator of viral replication and segregation factor for viral genomes. In addition to BRD4, a short form of BRD4 (BRD4S) is expressed from the BRD4 gene which lacks the C-terminal domain of BRD4. E2 proteins interact with the C-terminal motif (CTM) of BRD4, but a recent study suggested that the phospho-dependent interaction domain (PDID) and the basic interaction domain (BID) in BRD4 also bind to E2. These domains are also present in BRD4S. We now find that HPV31 E2 interacts with the isolated PDID domain in living cells and also with BRD4S which is present in detectable amounts in HPV-positive cell lines and is recruited into HPV31 E1 and E2 induced replication foci. Overexpression and knockdown experiments surprisingly indicate that BRD4S inhibits activities of E2. In line with that, the specific knockdown of BRD4S in the HPV31-positive CIN612-9E cell line induces mainly late viral transcripts. This occurs only in undifferentiated but not differentiated cells in which the productive viral replication cycle is induced. These data suggest that the BRD4S-E2 interaction is important to prevent HPV late gene expression in undifferentiated keratinocytes which may contribute to immune evasion and HPV persistence.ImportanceHuman papillomaviruses (HPV) have coevolved with their host by using cellular factors like bromodomain-containing protein 4 (BRD4) to control viral processes such as genome maintenance, gene expression and replication. We here show that, in addition to the C-terminal motif in BRD4, the phospho-dependent interaction domain in BRD4 interacts with E2 proteins which enable the recruitment of BRD4S, the short isoform of BRD4, to E2. Knock-down and overexpression of BRD4S reveals that BRD4S is a negative regulator of E2 activities. Importantly, the knockdown of BRD4S induces mainly L1 transcripts in undifferentiated CIN612-9E cells, which maintain replicating HPV31 genomes. Our study reveals an inhibitory role of BRD4S on HPV transcription, which may serve as an immune escape mechanism by the suppression of L1 transcripts and thus contribute to the establishment of persistent HPV infections.


Protein and Insulin Secretion in Diabetes.
In human beings, addition of protein and fat to a carbohydrate test diet decreases the rise in blood glucose while increasing the level of circulating insulin. Blood glucose elevation in response to arginine infusion gives a rough estimate of pancreatic capacity to release insulin.


Chitosan Extraction from Goliathus orientalis Moser, 1909: Characterization and Comparison with Commercially Available Chitosan.
Chitosan is a polymer obtained by deacetylation of chitin, and chitin is one of the major components of the arthropod cuticle. Chitin and chitosan are both polysaccharides and are considered to be an interesting class of biosourced materials. This is evident as chitosan has already demonstrated utility in various applications in both industrial and biomedical domains. In the present work, we study the possibility to extract chitin and prepare chitosan from the Goliath beetle Goliathus orientalis Moser. The presented work includes description of this process and observation of the macroscopic and microscopic variations that occur in the specimen during the treatment. The prepared chitosan is characterized and compared with commercially available chitosan using infrared and thermogravimetric analysis. The deacetylation degree of prepared chitosan is also evaluated and compared with commercially available shrimp chitosan.


Computational designing of the ligands of Protein L affinity chromatography based on molecular docking and molecular dynamics simulations.
Protein L is a multidomain protein from Peptostreptococcus magnus with binding affinity to kappa light chain of human immunoglobulin (Ig) which is used for the purification of antibody fragments by affinity chromatography. The advances in protein engineering and computational biology approaches lead to the development of engineered affinity ligands with improved properties including binding affinity. In this study, molecular dynamics simulations (MDs) and Osprey software were used to design single B domains of the Protein L with higher affinity to antibody fragments. The modified B domains were then polymerized to ligand with six B domains by homology modeling methods. The results showed that single B domain mutants of MB1 (Thr865Trp) and MB2 (Thr847Met-Thr865Trp) had higher binding affinity to Fab compared to the wild single B domain. Also, MDs and molecular docking results showed that the polymerized Proteins L including the wild and mutated six B domains (6B0, 6B1, and 6B2) were stable during MDs and the two mutants of 6B1 and 6B2 showed higher binding affinity to Fab relative to the wild type.Communicated by Ramaswamy H. Sarma.


Environmental cooperation system, ESG performance and corporate green innovation: Empirical evidence from China.
The Environmental Cooperation System (ECS) is a new exploration of the government's spatial environmental policy to meet the requirements of green and sustainable development, so it is very important to scientifically evaluate its green innovation effect. Based on China's A-share listed companies from 2006 to 2021, from the perspective of corporate ESG performance, we apply the multi-dimensional fixed-effects difference-in-differences (DID) model, and empirically test the impact, mechanism, and heterogeneity of the Environmental Cooperation System of Shenzhen-Dongguan-Huizhou Metropolis (ECS-SDHM) on corporate green innovation. It found that ECS-SDHM can significantly improve corporate green innovation, and the policy effect is more significant in the private enterprise group. Secondly, we use ESG rating score and decomposition indicators to deeply analyze the green innovation effect mechanism of ECS-SDHM from the perspective of ESG performance. The results show that ECS-SDHM can enhance corporate green innovation by significantly improving corporate ESG performance, environmental governance, and social governance. Further research found that both corporate environmental social responsibility and executives' overseas backgrounds can positively moderate the green innovation effect of ECS-SDHM by positively moderating the ESG performance mechanism.


Distribution of decidual mast cells in fetal growth restriction and stillbirth at (near) term.
Placental pathology and pregnancy complications are associated with unfavorable regulation of the maternal immune system. Although much research has been performed towards the role of immune cells like macrophages and T cells in this context, little is known about the presence and function of mast cells (MC). MC can be sub classified in tryptase-positive (MCT) and tryptase- and chymase-positive (MCTC). This study investigates the presence of MC in the decidua of pregnancies complicated by fetal growth restriction (FGR) and stillbirth (SB). Placental tissue from FGR (n = 250), SB (n = 64) and healthy pregnancies (n = 42) was included. Histopathological lesions were classified according to the Amsterdam Placental Workshop Group criteria. Tissue sections were stained for tryptase and chymase. Decidual MC were counted manually, and the results were expressed as number of cells/mm2 decidual tissue. A significant lower median number of MCTC was found in the decidua of FGR (0.40 per mm2; p < 0.001) and SB (0.51 per mm2; p < 0.05) compared to healthy controls (1.04 per mm2). No difference in MCT number (1.19 per mm2, 1.88 per mm2 and 1.37 per mm2 respectively) was seen between the groups. There was no difference in number of MCT and MCTC between placental pathological lesions. Our findings suggest a shift in decidual MC balance towards MCT in pregnancy complications. No difference in numbers of MC subtypes was found to be related to histopathologic lesions.


[The acute management of agitation].
Agitation in psychiatry is defined as "a request to which an answer cannot be deferred". If some types of controllable agitation can be solved by human means or psychotropic drugs, others may require the intervention of intensivists who will contribute to the onset of crisis resolution. In addition, an organic aetiology must be carefully excluded a before considering a psychiatric origin of agitation, especially in patients with no psychiatric history and in the elderly. Indeed, acute agitation can hide serious somatic traps and be life threatening.


Technology-Intensified Diabetes Education Study (TIDES) in African Americans with type 2 diabetes: study protocol for a randomized controlled trial.
Compared to American Whites, African Americans have a higher prevalence of type 2 diabetes mellitus (T2DM), experiencing poorer metabolic control and greater risks for complications and death. Patient-level factors, such as diabetes knowledge, self-management skills, empowerment, and perceived control, account for >90% of the variance observed in outcomes between these racial groups. There is strong evidence that self-management interventions that include telephone-delivered diabetes education and skills training are effective at improving metabolic control in diabetes. Web-based home telemonitoring systems in conjunction with active care management are also effective ways to lower glycosylated hemoglobin A1c values when compared to standard care, and provide feedback to patients; however, there are no studies in African Americans with poorly controlled T2DM that examine the use of technology-based feedback to tailor or augment diabetes education and skills training. This study provides a unique opportunity to address this gap in the literature. We describe an ongoing 4-year randomized clinical trial, which will test the efficacy of a technology-intensified diabetes education and skills training (TIDES) intervention in African Americans with poorly controlled T2DM. Two hundred male and female AfricanAmerican participants, 21 years of age or older and with a glycosylated hemoglobin A1c level ≥ 8%, will be randomized into one of two groups for 12 weeks of telephone interventions: (1) TIDES intervention group or (2) a usual-care group. Participants will be followed for 12 months to ascertain the effect of the interventions on glycemic control. Our primary hypothesis is that, among African Americans with poorly controlled T2DM, patients randomized to the TIDES intervention will have significantly greater reduction in glycosylated hemoglobin A1c at 12 months of follow-up compared to the usual-care group. Results from this study will add to the current literature examining how best to deliver diabetes education and skills training and provide important insight into effective strategies to improve metabolic control and hence reduce diabetes complications and mortality rates in African Americans with poorly controlled T2DM. This study was registered with the National Institutes of Health Clinical Trials Registry on 13 March 2014 (ClinicalTrials.gov identifier# NCT02088658).


Supra-Cyanines: Ultrabright Cyanine-Based Fluorescent Supramolecular Materials in Solution and in the Solid State.
Fluorescent materials with high brightness play a crucial role in the advancement of various technologies such as bioimaging, photonics, and OLEDs. While significant efforts are dedicated to designing new organic dyes with improved performance, enhancing the brightness of existing dyes holds equal importance. In this study, we present a simple supramolecular strategy to develop ultrabright cyanine-based fluorescent materials by addressing long-standing challenges associated with cyanine dyes, including undesired cis-trans photoisomerization and aggregation-caused quenching. Supra-cyanines are obtained by incorporating cyanine moieties in a cyclic peptide-based supramolecular scaffold, and exhibit high fluorescence quantum yields (up to 50 %) in both solution and in the solid state. These findings offer a versatile approach for constructing highly emissive cyanine-based supramolecular materials.


Analysis of Dermatologic Diseases in Neurosurgical In-Patients: A Retrospective Study of 463 Cases.
Both the skin and the neurologic system are derived from the ectoderm during embryogenesis, and thus patients with neurologic disorders may have accompanying dermatologic diseases. For example, seborrheic dermatitis is more frequently observed in patients with Parkinsonism and other neurologic disorders. To date, however, there has been limited review on dermatologic diseases in neurosurgical in-patients. The purpose of this study was to characterize dermatological problems encountered in a neurosurgery unit and to compare these data to previous reports of in-patient dermatologic consultations. A retrospective review was conducted over all in-patient dermatology consultations from the neurosurgery unit during a 3-year period. Of 2,770 dermatology consultations, 463 (16.7%) came from the department of neurosurgery. The most frequent age group was the 6th decade of life, and the ratio of men to women was 1.07. Consults were most frequently placed from patients with intracranial hemorrhage (23.8%). Eczema/dermatitis (36.5%; n=204) and cutaneous infections (27.0%; n=151) accounted for more than half of all dermatological consultations, followed by cutaneous adverse drug reactions (11.8%; n=66). Additionally, seborrheic dermatitis was significantly more frequent (p=0.048, odds ratio=1.96) in patients with intracranial hemorrhage. This study characterizes the distribution of skin disorders in patients admitted to the neurosurgery service based on the consultations that have been made for dermatologic evaluation. Collaboration between the neurosurgeons and dermatologists may improve the quality of patient care and help to better predict the occurrence of these conditions.


Pyopericardium and extensive mediastinal abscess following EBUS-TBNA for mediastinal staging of NSCLC: a case report.
Based on the algorithm on preoperative mediastinal staging in patients with non-small cell lung cancer (NSCLC), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is indicated in case of computed tomography (CT)-enlarged or positron emission tomography (PET)-positive mediastinal lymph nodes. It represents both a safe minimal invasive procedure with complication rates of less than 1.5% and a valid tool with a high sensitivity defining mediastinal nodal disease. However, infectious complications like mediastinitis or pyopericardium are most feared. A 54-year-old woman was admitted to our hospital for further investigation of a suspected NSCLC of the right upper lobe. EBUS-TBNA was performed to receive both diagnosis and samples of the mediastinal lymph nodes. Two weeks after EBUS-TBNA, the patient presented with symptoms of cardiogenic/septic shock: hypotension, tachycardia, chest pain and fever. Prompt diagnosis of concomitant infectious mediastinitis and extensive pyopericardium in consequence of EBUS-TBNA was obvious. Besides systemic antibiotics, bilateral thoracoscopic interventions finally made the breakthrough. The patient could be discharged roughly three weeks after emergent re-admittance. As being finally diagnosed with NSCLC (stage IIIA squamous cell carcinoma), the patient underwent-subsequent to induction chemotherapy-a definitive sequential chemoradiotherapy. Twelve-month follow-up confirmed stable disease. It is to be expected that with increasing application of EBUS-TBNA as mediastinal staging tool, the number of serious infection-related complications will rise accordingly. The efficacy of antibiotic prophylaxis after EBUS-TBNA has not yet been proved and is therefore not included in any guideline. Our case gives an impression on the severity of delayed infectious complications after EBUS-TBNA and outlines up-front surgery as primary objective to broadly debride all contagious abscess-/empyema sites. With increased use of EBUS-TBNA as mediastinal staging tool, clinicians should be aware of this rare but highly critical peri-interventional complication in order to closely monitor endangered patients.


Integrating New Therapies for Chronic Lymphocytic Leukemia.
Over the last 2 decades, treatment of chronic lymphocytic leukemia (CLL) therapy has drastically changed, resulting in greatly improved survival and treatment tolerance with current targeted therapies. First, the transition from chemotherapy (alkylating agents, nucleoside analogs) to chemoimmunotherapy with the addition of anti-CD20 antibodies resulted in deeper and more complete remissions, with an improvement in progression-free and overall survival. Over the last few years, chemoimmunotherapy has gradually been replaced by new targeted agents, based on further improvement in survival, especially in patients with high-risk CLL, and fewer adverse effects, that is, a lack of myelosuppression and lack of DNA damage and associated risk of secondary acute myeloid leukemia/myelodysplastic syndrome. The most active targeted treatments for CLL patients are the kinase inhibitors, which inhibit signaling of surface receptors, especially the B-cell antigen receptor, and the BCL-2 antagonist venetoclax. Among the kinase inhibitors, Bruton tyrosine kinase inhibitors are highly effective and generally well-tolerated and induce durable responses in the vast majority of patients. PI3 kinase inhibitors are alternatives for patients with intolerance to Bruton tyrosine kinase inhibitors. This review discusses the rationale for the transition from chemotherapy-based treatment to the novel agents, the activity, adverse effects, sequencing, and combinations of the novel agents and provides an outlook into future CLL therapy for the next decade.


Benefits of a beta-blocker for intractable hemolysis due to paraprosthetic leakage.
We describe a 58-year-old man who was successfully treated with a beta-adrenergic receptor blocking agent for intractable hemolysis due to paraprosthetic leakage. After replacement of a mitral prosthetic valve with another mechanical valve, the patient suffered intractable intravascular hemolysis resulting from recurrent paraprosthetic leakage. With oral administration of a beta-adrenergic receptor blocker, betaxolol hydrochloride, for 3 months, the hemoglobin value increased from 9.7 g x dL(-1) to 12.4 g x dL(-1), although glutamic oxaloacetic transaminase and lactic dehydrogenase values remained elevated.


Intrathecal hyperbaric bupivacaine dose response in postpartum tubal ligation patients.
Because of its short duration, hyperbaric lidocaine has been a popular intrathecal drug to provide anesthesia for postpartum tubal ligation (PPTL). However, reports of transient symptoms associated with its use have prompted the search for alternative intrathecal local anesthetics for short procedures. Hyperbaric bupivacaine is rarely associated with transient neurologic symptoms, and we designed this study to determine the optimal dose of bupivacaine for PPTL that assures adequate sensory block and allows the patient the shortest recovery time. Forty American Society of Anesthesiologists (ASA) I-II patients undergoing spinal anesthesia for PPTL were randomly assigned to receive 5.0, 7.5, 10.0, or 12.5 mg hyperbaric bupivacaine in the right lateral position. Despite sensory block above T-8 in all groups, 4 of the 5 patients in the 5-mg group developed blocks insufficiently dense for surgery and required general anesthesia. Failed spinals occurred evenly in the remaining groups. Motor regression was significantly more rapid with decreasing doses of bupivacaine. Time in the postanesthesia care unit (PACU) was shorter in the 7.5-mg group. Hyperbaric bupivacaine 7.5 mg injected in the lateral position provides adequate surgical anesthesia for PPTL with a minimal duration of motor block and recovery time.


The clinical effectiveness and cost-effectiveness of fractional CO2 laser in acne scars and skin rejuvenation: A meta-analysis and economic evaluation.
Fractional CO2 has many indications in medicine including in treatment of acne scars and rejuvenation. The aim of this study was to evaluate the safety, efficacy, and cost-effectiveness of Fractional CO2 Laser in comparison with other methods of rejuvenation and acne scar treatment. Several databases including Medline, OVID, EMBASE, CINHAL, SCOPUS, Web of science, CRD, and Cochrane were searched. After conducting the search and evaluation of selected publications, critical appraisal was done and eligible studies were accepted for inclusion in the systematic review. From 2667 identified publications two of the trials were eligible. The effectiveness and complications of Fractional CO2 laser were comparable with Er:YAG but Fractional CO2 laser was 14.7% (p = 0.01) more effective than Q-Switched ND:YAG laser. Cost affectivity of this method was the same as other alternative lasers. In conclusion Fractional CO2 laser is an effective and safe method for curing of several kinds of skin diseases. Nevertheless there was not sufficient evidence to support its advantage. This device has equal or lower price in comparison to competent technologies except for the non- fractional ablative CO2 laser that has the same or lower price and comparable effects.


[Effect of salvianolic acid B on neural cells damage and neurogenesis after brain ischemia-reperfusion in rats].
This study is to observe the effect of salvianolic acid B (Sal B) on neural cells damage and neurogenesis in sub-granular zone (SGZ) and sub-ventricular zone (SVZ) after brain ischemia-reperfusion (I/R) in rats. A modified middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion was used. The rats were divided into four groups: sham control group, ischemia-reperfusion group, Sal B 1 and 10 mg x kg(-1) groups. Sal B was consecutively administrated once a day by ip injection after MCAO. The neurogenesis in SGZ and SVZ was investigated by BrdU method 7 days after MCAO. The Nissl staining for neurons in the hippocampal CA1 and cerebral cortex was performed 14 days after MCAO. A beam-walking test was used to monitor the motor function recovery. We found that brain ischemia resulted in an increase of BrdU positive cells both in ipsilateral SGZ and SVZ at 7th day after MCAO. Sal B (10 mg x kg(-1)) significantly increased further the number of BrdU positive cells both in SGZ and SVZ (P < 0.01). Ipsilateral hippocampal neuron damage occurred and CA1 almost lost 14 days after MCAO. Sal B (10 mg x kg(-1)) obviously attenuated the neuron damage and increased the number of neuron both in ipsilateral CA1 and cerebral cortex (P < 0.01). We also observed an obvious improvement of motor function recovery when Sal B (10 mg x kg(-1)) administrated. From the results above we concluded that Sal B stimulated neurogenesis process both in SGZ and SVZ after brain ischemia, and also alleviated neural cells loss and improved motor function recovery after brain ischemia in rats.


Incidence and forms of EPH gestosis in twin pregnancy.
An increased incidence of EPH gestosis in twin pregnancies is frequently reported. During the past 12 years, 188 women gave birth to twins in our hospital. For these mothers, the incidence of EPH gestosis on admission was 42.5%, in contrast to 31.4% for a control group matched for age, parity and nationality. EPH gestosis occurring in twin pregnancies was more severe than that in single pregnancies.


Role Discovery-Guided Network Embedding Based on Autoencoder and Attention Mechanism.
Recently, network embedding (NE) is an amazing research point in complex networks and devoted to a variety of tasks. Nearly, all the methods and models of NE are based on the local, high-order, or global similarity of the networks, and few studies have focused on the role discovery or structural similarity, which is of great significance in spreading dynamics and network theory. Meanwhile, existing NE models for role discovery suffer from two limitations, that is: 1) they fail to model the varying dependencies between each node and its neighbor nodes and 2) they cannot capture the effective node features which are helpful to role discovery, which makes these methods ineffective when applied to the role discovery task. To solve the above problems of NE for role discovery or structural similarity, we propose a unified deep learning framework, called RDAA, which can effectively represent features of nodes and benefit the Role Discovery-guided NE with a deep autoencoder, while modeling the local links with an Attention mechanism. In addition, we design an elaborately binding technique to combine both parts and optimize the framework in a unified way. We conduct different experiments, including visualization, role classification, role discovery, and running time compared to popular NE methods for both proximity and structural similarity. The RDAA has better performance on all the datasets and achieves good tradeoffs.


The identification of four protein kinase C isoforms in human glioblastoma cell lines: PKC alpha, gamma, epsilon, and zeta.
Levels of protein kinase C (PKC) isoforms in eight human glioblastoma cell lines and two normal human glial cell cultures were determined. Earlier studies identified PKC-alpha and PKC-gamma in these cell lines but PKC-beta was not present. In this study, PKC-epsilon and PKC-zeta are demonstrated immunologically in these cell lines and also in two normal human glial cell cultures. Protein kinase C-delta was not present. When levels of the four isoforms in the tumor cells were compared to levels in the normal cells, no increase was observed in PKC-alpha or PKC-gamma, but PKC-epsilon was elevated three to 30 times in six of the eight tumors, and PKC-zeta was elevated approximately two times in all of the tumors. Incubation of cell line A172 with phorbol ester for 6 hours resulted in a 48-fold maximum increase in the nuclear PKC-epsilon and a sevenfold increase in the plasma membrane fraction with no change in the cytoplasmic fraction. A similar incubation for 4 hours produced a 0.5- to onefold increase of PKC-zeta in cytoplasmic, nuclear, and plasma membrane fractions. Other researchers have shown that overexpression of PKC-epsilon in fibroblasts results in tumorigenesis, and that blocking PKC-zeta function inhibits deoxyribonucleic acid synthesis. These data suggest that alteration in the expression of PKC-epsilon and PKC-zeta could be a factor in the conversion of normal glial cells to glioblastomas.


Comprehensive policies for victims of sexual assault returning to the campus classroom: Lessons from university sports-related concussion policies.
ObjectiveThe current paper presents a comparison of university policies and health and academic accommodations offered to undergraduate students following sexual assault (SA) and sports-related concussions (SRC). Procedures and protocols for universities to consider adapting from their SRC policies to their SA policies are detailed.Participants: The SRC and SA policies at the 50 United States public flagship universities were analyzed.Methods: The research team coded for a number of policy details including health referrals, academic and financial accommodations, and requirements for follow-up with university personnel.Results: Compared to SA polices, SRC policies at the public flagship universities offer more comprehensive academic accommodations and physical and mental health resources. Conclusions: Comprehensive policies for student SA survivors, like those available for students who suffer SRCs, would improve student health and academic outcomes and increase SA survivors' likelihood of graduating college, thereby reducing individual and societal human capital loses.


Tuning MOF CO2 adsorption properties via cation exchange.
The pore volume and BET surface area of bio-MOF-1 (a), Zn(8)(ad)(4)(BPDC)(6)O.2Me(2)NH(2), is systematically modified via postsynthetic cation exchange with either tetramethylammonium, tetraethylammonium, or tetrabutylammonium cations to yield Zn(8)(ad)(4)(BPDC)(6)O.2Me(4)N (b), Zn(8)(ad)(4)(BPDC)(6)O.2Et(4)N (c), and Zn(8)(ad)(4)(BPDC)(6)O.2Bu(4)N (d), respectively. The impact that pore volume and BET surface area have on CO(2) capacity is evaluated, and it is found that materials with intermediate porosity (b and c) have the largest CO(2) capacities under the conditions studied.


Sonographic diagnosis of an unusual case of multilocular cystic nephroma mimicking polycystic kidney disease.
The following is a report of the unusual case of a multilocular cystic nephroma in an 8-year-old boy who was transferred to our unit with a palpable abdominal tumor. The patient suffered from thoracic pain and night sweating. The laboratory values were normal. Abdominal sonography showed a huge kidney tumor on the right side consisting of numerous small cysts transversed by irregular septa of variable thickness. The cysts had a diameter of 1 -5 mm; larger cysts of more than 1 cm in diameter were not able to be shown. In the center of the tumor a normal renal parenchyma was able to be shown. The tumor arose like a mushroom from the kidney. Color Doppler sonography showed good vascularity of the normal renal parenchyma while the tumor had only a few internal vessels. The tumor was surgically removed. The histologic diagnosis was cystic nephroma. Unusual features of this tumor were the small size of the numerous cysts similar to polycystic kidney disease and the mushroom-like growth of the tumor.


Macromolecular crowding effects on electrostatic binding affinity: Fundamental insights from theoretical, idealized models.
The crowded cellular environment can affect biomolecular binding energetics, with specific effects depending on the properties of the binding partners and the local environment. Often, crowding effects on binding are studied on particular complexes, which provide system-specific insights but may not provide comprehensive trends or a generalized framework to better understand how crowding affects energetics involved in molecular recognition. Here, we use theoretical, idealized molecules whose physical properties can be systematically varied along with samplings of crowder placements to understand how electrostatic binding energetics are altered through crowding and how these effects depend on the charge distribution, shape, and size of the binding partners or crowders. We focus on electrostatic binding energetics using a continuum electrostatic framework to understand effects due to depletion of a polar, aqueous solvent in a crowded environment. We find that crowding effects can depend predictably on a system's charge distribution, with coupling between the crowder size and the geometry of the partners' binding interface in determining crowder effects. We also explore the effect of crowder charge on binding interactions as a function of the monopoles of the system components. Finally, we find that modeling crowding via a lowered solvent dielectric constant cannot account for certain electrostatic crowding effects due to the finite size, shape, or placement of system components. This study, which comprehensively examines solvent depletion effects due to crowding, complements work focusing on other crowding aspects to help build a holistic understanding of environmental impacts on molecular recognition.


The Oral health status of children with autism Spectrum disorder in KwaZulu-Nata, South Africa.
Echoing the sentiments of the Sixty-seventh World Health Assembly of May 2014, mandating the all-inclusive and synchronized efforts for the management of autism spectrum disorder (ASD), the aim of this current study was to investigate the oral health status of children with ASD aged between 7 to 14 years in KwaZulu-Natal, South Africa. An investigative cross-sectional quantitative design employing non-probability purposeful sampling was conducted on 149 children with ASD attending special needs schools in KwaZulu-Natal. An intra-oral examination to investigate decayed, missing and filled teeth (DMFT/dmft), gingival index (GI), and plaque index (PI), attrition and soft tissue trauma using the World Oral Health Survey Form for Children, (2013) was implemented during data collection. Average DMFT/dmft scores of 3, 42 and 0, 97 were recorded respectively. Molars dominated the decayed component of the DMFT/dmft with an average caries prevalence of (51, 7% and 40, 8%) respectively. These results displayed zero fillings indicative of unmet treatment needs. The gingival index revealed mild gingival inflammation, (46, 3%) and the plaque index demonstrated visible plaque at (43, 6%).Attrition scores revealed mild loss of dental enamel (47%). The most prevalent soft tissue trauma recorded was lip biting (37, 25%). Restorative or preventative treatment measures were not evident in this study. Unmet dental needs are therefore an important concern in this population. Health care planners should develop preventive programs targeted at high risk groups such as this study population.


[The significance of the serum tumour markers as a prognostic and predictor factors in nonsmall cell lung cancer patients].
The aim of the study was to assess the role of serum tumour markers (NSE, Cyfra 21-1, CEA, LDH, ferritin) as a prognostic and predictive factors in 79 patients with advanced NSCLC treated with chemotherapy. Objective response to treatment was significantly more frequent in the patient with serum NSE > 12.5 ng/ml. Progression of disease was observed more often in patients with serum Cyfra 21-1 >10 ng/ml or LDH >480 U/L. CEA >3 ng/ml, LDH >480 U/L, for coefficient >1, NSE >20 ng/ml and Cyfra 21-1 >10 ng/ml had a negative impact on survival in univariate analysis. Independent negative prognostic significance of fer coefficient >1 was confirmed by multivariate analysis.


[Doppler frequency spectrum analysis of extracranial carotid artery lesions].
Signals registered from the extracranial carotid artery by direct Doppler-ultrasound with a MHz transducer were subjected to real-time frequency spectrum analysis. A systolic maximal frequency over 3500 Hz was considered abnormal, together with a broadened spectrum. The study was made on 157 subsequently operated carotid arteries, not all of which had previous angiographic studies. Of 47 with a normal angiogram 45 were correctly classified non-invasively (specificity 96%). The non-invasive diagnosis was correct in 16 of 17 occlusions of the internal carotid artery demonstrated angiographically. An abnormal Doppler frequency analysis was present in only 7 of 14 stenoses with a decreased vessel lumen below 25%. An abnormal Doppler frequency analysis was present in 78 of 79 stenoses with more than 25% reduction in lumen diameter, diagnostic sensitivity for all stenoses being 91%.


Paroxetine Administration Affects Microbiota and Bile Acid Levels in Mice.
Recent interest in the role of microbiota in health and disease has implicated gut microbiota dysbiosis in psychiatric disorders including major depressive disorder. Several antidepressant drugs that belong to the class of selective serotonin reuptake inhibitors have been found to display antimicrobial activities. In fact, one of the first antidepressants discovered serendipitously in the 1950s, the monoamine-oxidase inhibitor Iproniazid, was a drug used for the treatment of tuberculosis. In the current study we chronically treated DBA/2J mice for 2 weeks with paroxetine, a selective serotonin reuptake inhibitor, and collected fecal pellets as a proxy for the gut microbiota from the animals after 7 and 14 days. Behavioral testing with the forced swim test revealed significant differences between paroxetine- and vehicle-treated mice. Untargeted mass spectrometry and 16S rRNA profiling of fecal pellet extracts showed several primary and secondary bile acid level, and microbiota alpha diversity differences, respectively between paroxetine- and vehicle-treated mice, suggesting that microbiota functions are altered by the drug. In addition to their lipid absorbing activities bile acids have important signaling activities and have been associated with gastrointestinal diseases and colorectal cancer. Antidepressant drugs like paroxetine should therefore be used with caution to prevent undesirable side effects.


Performance characteristics of an FT MS-based workflow for label-free differential MS analysis of human plasma: standards, reproducibility, targeted feature investigation, and application to a model of controlled myocardial infarction.
Proteomics is undergoing a rapid transformation from a qualitative global peptide sequencing discipline into a quantitative, reproducibility-driven practice. Nowhere is this more evident than in the rapidly expanding field of protein biomarker discovery where the general goal is to uncover statistically robust patterns of differential expression between or among subjects/samples representing distinct biological/temporal states. This report presents the analytical characterization of a label-free LC FT-ICR-MS workflow for differential proteomics analysis of human plasma. The key elements discussed include (i) methodologies for performing properly replicated experiments with highly reproducible sample preparation and analysis, including the use of internal standards to quantify variance at different steps in the process, (ii) a new methodology for performing sample re-analysis that uses off-line targeted robotic acquisition of complementary spectral data (e.g. ECD and/or IRMPD) to enhance the identification of differentially expressed peptides/proteins, and (iii) data processing pipelines capable of integrating the automatic statistical analysis of the label-free (LC-) MS signal, together with the intuitive and highly interactive curation and annotation of differential features using the output from standard sequence database search programs. We illustrate the application of the complete sample-to-annotated-differential-peptides (-proteins) workflow by describing the acquisition and analysis of a large multidimensional dataset from patients undergoing a controlled myocardial infarction resulting in an experimental setup in which each patients serve as their own control. Furthermore, we discuss a couple illustrative examples of mid-level proteins observed in this study whose plasma concentrations change consistently within and across patients, in a treatment- and time-dependent fashion.


Emotionally-intense situations can result in rhabdomyolysis in McArdle disease.
Despite the majority of patients with McArdle disease reporting symptoms including fatigue, cramps and episodes of myoglobinuria from early childhood, diagnosis is often delayed by several decades. Additionally, many individuals with rhabdomyolysis remain undiagnosed. The occurrence of symptoms during exercise, particularly isometric muscle contraction such as heavy lifting, is well known in McArdle disease. However, isometric muscle contraction that occurs with emotion is not recognised as exercise and may be missed as a trigger for rhabdomyolysis, potentially leading to a delay in diagnosis. Three patients are presented here, all with symptoms from childhood including episodes of rhabdomyolysis induced by tense emotional situations without physical exertion; two patients reported recurrent episodes while watching rather than playing football. The remaining patient developed rhabdomyolysis during a heated argument. These patients' histories emphasise the risk from sustained isometric muscle contraction that occurs in emotive situations for patients with McArdle disease.


Estrogen Signaling Dictates Musculoskeletal Stem Cell Behavior: Sex Differences in Tissue Repair.
Sexual dimorphisms in humans and other species exist in visually evident features such as body size and less apparent characteristics, including disease prevalence. Current research is adding to a growing understanding of sex differences in stem cell function and response to external stimuli, including sex hormones such as estrogens. These differences are proving significant and directly impact both the understanding of stem cell processes in tissue repair and the clinical implementation of stem cell therapies. Adult stem cells of the musculoskeletal system, including those used for development and repair of muscle, bone, cartilage, fibrocartilage, ligaments, and tendons, are no exception. Both in vitro and in vivo studies have found differences in stem cell number, proliferative and differentiation capabilities, and response to estrogen treatment between males and females of many species. Maintaining the stemness and reducing senescence of adult stem cells is an important topic with implications in regenerative therapy and aging. As such, this review discusses the effect of estrogens on musculoskeletal system stem cell response in multiple species and highlights the research gaps that still need to be addressed. The following evidence from investigations of sex-related phenotypes in adult progenitor and stem cells are pieces to the big puzzle of sex-related effects on aging and disease and critical information for both fundamental tissue repair and regeneration studies and safe and effective clinical use of stem cells. Impact Statement This review summarizes current knowledge of sex differences in and the effects of estrogen treatment on musculoskeletal stem cells in the context of tissue engineering. Specifically, it highlights the impact of sex on musculoskeletal stem cell function and ability to regenerate tissue. Furthermore, it discusses the varying effects of estrogen on stem cell properties, including proliferation and differentiation, important to tissue engineering. This review aims to highlight the potential impact of estrogens and the importance of performing sex comparative studies in the field of tissue engineering.


Transparency and choice in learning healthcare systems.
Learning healthcare systems rely on potentially sensitive data and biospecimens from patients who typically have no knowledge of secondary uses of these resources for research. While this failure to inform patients of these practices is consistent with human subject regulations for research, these practices risk controversy and a loss of trust in the integrity of healthcare institutions. This article reviews recent controversies in this domain and argues for new institutional practices that entail patient education about secondary uses of data and biospecimens and the opportunity for patient choice in the form of an opt-out system. This approach would enhance transparency and reduce the risk of a loss of public trust in the research enterprise.


Prostate cancer: serum and tissue markers.
The detection of prostate cancer, its clinical staging, and the prediction of its prognosis remain topics of paramount importance in clinical management. The digital rectal exam, although once the "gold standard," has been largely supplanted by a variety of techniques including serum and tissue-based assays. This article reviews recent progress in the development of prostate-specific antigen assays with greater specificity; molecular markers for prostate cancer (DNA ploidy, nuclear morphometry, markers of proliferation, and cell adhesion molecules); the link between vitamin D deficiency and the clinical emergence of prostate cancer; the possible correlation of serum insulin-like growth factor levels with the risk for developing prostate cancer; and the latest advances in radiologic staging.


Clinical features and severity of nonspecific symptoms in dialysis patients.
Nonspecific symptoms are common in dialysis patients but few methods are available to measure their severity and their response to alteration in dialysis therapy. To determine the clinical features and measure the severity of the most important symptoms in end-stage renal disease (ESRD) patients, 97 dialysis patients were interviewed, 63 of whom were reinterviewed 1 year later. For comparison 82 transplant recipients were also interviewed. The six most important symptoms in dialysis patients (using the product of the patient's perception of severity and prevalence) were tiredness, cramps, pruritus, dyspnea, headaches and joint pain. The symptoms were long-standing, occurred frequently, with little difference in prevalence between hemo- and peritoneal dialysis patients, and were often unrelated to a hemodialysis session. For each symptom, several dimensions of severity were assessed including frequency, duration, effect on sleep, daily living, activity, subjective quality of life and necessity for drug therapy. Often these dimensions did not correlate with patient's perception of severity. For each symptom these items were combined to give an aggregate score with a range 0-10. Interobserver reproducibility for each symptom score was greater than or equal to 0.7 but intraobserver reproducibility was poor for 3 symptoms, because of the fluctuating nature of the symptoms. Construct validity was demonstrated by finding a significantly worse distribution of aggregate scores for tiredness, cramps, pruritus, dyspnea and nausea/vomiting in dialysis compared to transplant patients. Aggregate scores changed little after 1 year's follow-up in stable dialysis patients but significant improvement in the aggregate scores for tiredness, dyspnea and nausea/vomiting were observed in 14 patients after successful transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)


Implications of platinum-group element accumulation along U.S. roads from catalytic-converter attrition.
Automobile catalytic converters are dispersing platinum-group elements (PGEs) Rh, Pt, and Pd into the environment (1-3). This paper represents the first detailed study to assess the PGE content of soils and grasses from U.S. roadsides. These soils were analyzed using cation exchange pretreatment and ultrasonic nebulizer-ICP-MS (4). Highway and several urban sites showed Pt abundances of 64-73 ng/g immediately adjacent to the roadside, with corresponding Pd and Rh abundances of 18-31 ng/g and 3-7 ng/g, respectively. All Pt and most Pd and Rh abundances are statistically above local background soil values. Platinum, Rd, and Rh show positive correlations with traffic-related elements (Ni, Cu, Zn, and Pb) but no correlations with nontraffic-related elements (Y, Ga). Iridium and Ru show no correlations with any of these trace elements. These PGE abundances are comparable to European studies (5-7) and are approaching concentrations that would be economically viable to recover. This study also demonstrates transport of Pt statistically above background more than 50 m from the roadside. Further study is necessary to see how mobile the PGEs are in roadside environments, but these initial data indicate only Pt is taken up by plants.


Prevalence and frequency of mental health care provided by general practitioners: differences between 2 national data sources for the same population.
Estimates from Canada's first national mental health surveillance initiative-which is based on diagnostic codes in administrative health care utilization databases-indicate that the proportion of Canadians who receive mental health care is more than twice as high as reported in Canada's national mental health survey. Our study examines and clarifies the nature and extent of differences between 2 predominant types of data that are used for mental health services research and planning. A person-by-person data linkage was conducted between the Canadian Community Health Survey: Mental Health and Well-Being and administrative health care utilization records (British Columbia Ministry of Health Services-Medical Services Plan, and Hospital Discharge Abstract Database) within a universal-access, publically funded health care system, to examine the level of agreement between the data sources and respondent characteristics associated with agreement (N = 2378). The prevalence of mental health care from general practitioners (GPs) was higher in administrative data (19.3%; 95% CI 17.7% to 20.9%) than survey data (8.5%; 95% CI 7.5% to 9.8%). Agreement between prevalence estimates from the 2 data sources was associated with age, mental health characteristics, and the number of GP visits. The median number of visits per person was significantly higher in the survey data. GPs saw more than twice as many patients for mental health issues according to administrative data, compared with survey data; however, the number of visits per patient was higher in survey data.


Oridamycins A and B, anti-Saprolegnia parasitica indolosesquiterpenes isolated from Streptomyces sp. KS84.
Oridamycins A (1) and B (2) were isolated from the fermentation broth of Streptomyces sp. strain KS84 as selective anti-Saprolegnia parasitica antibiotics. Their structures were elucidated as pentacyclic indolosesquiterpenes by the combination of NMR and spectroscopic analyses. The absolute configuration of 1 was determined by ROESY analyses after the advanced Mosher analysis. Compound 1 exhibited anti-S. parasitica activity with an MIC value of 3.0 microg/mL, but was much less active against the phytopathogenic fungus Phoma sp. and the yeast Saccharomyces cerevisiae.


Incidence of Type 2 Diabetes Mellitus among Emirati Residents in Ajman, United Arab Emirates.
Diabetes mellitus (DM), particularly type-2 is a major public health concern worldwide. Not much information is available with regard to the incidence of DM in United Arab Emirates (UAE). This study aimed at determining the incidence rate of diabetes mellitus among Emirati population in Ajman, UAE. This is a retrospective cohort study. This study was conducted in all primary health care centers and Shaikh Khalifa and GMC Hospitals, Ajman, UAE where the Emirati population primarily go for diagnosis and treatment. The incident cases of diabetes mellitus were collected during the period 2010 January to December. A total of 158 cases newly detected in 2010, 54 were among non-Emiratis and one was type-1 diabetes. Eliminating these, the remaining 101 were included in the analysis. The age of the patients ranged from 23 years to 78 years; 35 (34.7%) males and 66 (65.3%) were females. The overall incidence observed was 4.8/1,000 person-years (PY) with a female predominance of 6.3/1,000 PY against incidence among males of 3.3/1,000 PY. With regard to age specific incidence rate among males, it increases with age till 60 years and then showed a decreasing trend. Among females also the same trend was observed but not as similar to males. The highest incidence rate was observed in the 55-59 age group among males, 23.4/1,000 PY and females, 32.4/1,000 PY. Among males the incidence rate was much less compared to females in-the age groups older than 59 years.


Evidence for alterations to dynamic quantitative sensory tests in patients with chronic temporomandibular myalgia: A systematic review of observational studies with meta-analysis.
Conflicting results exist between somatosensory profiles of patients with temporomandibular myalgia (TMDm). The objective of this review was to examine whether adults with TMDm show altered responses to dynamic quantitative sensory tests compared with healthy controls. We searched five electronic databases for studies, excluding those without suitable controls or where TMDm was associated with confounding non-musculoskeletal disorders. Risk of bias was assessed with the SIGN case-control study checklist. Findings were structured around dynamic quantitative sensory tests and their localization. Where possible, we performed meta-analysis with a random inverse variance model to compare patients with TMDm and healthy controls. Statistical heterogeneity was estimated with Chi² test and inconsistency index, I². We extracted data from 23 studies comprising 1284 adults with chronic TMDm and 2791 healthy controls. Risk of bias was assessed as high for 20 studies. Mechanical temporal summation, the most studied phenomenon (14 studies), is increased in the upper limb of patients with TMDm (SMD = 0.43; 95% CI: .11 to .75; p = .009) but not in the jaw area (p = .09) or in the cervical area (p = .29). Very little evidence for altered thermal temporal summation (five studies), conditioned pain modulation (seven studies), exercise-induced hypoalgesia (two studies), placebo analgesia (two studies), stress-induced hypoalgesia (one study) and offset analgesia (one study) was found. A major limitation of this review was the risk of bias of included studies. Future studies would benefit from following methodological guidelines and consideration of confounding factors.


An algorithm for diagnosis and treatment of status epilepticus in adults.
Convulsive or generalized tonic-clonic status epilepticus (SE) is a neurological emergency that can lead to transient or permanent brain damage or even death. A conceptual model was developed to assist nurses and other medical professionals to differentiate between convulsive and nonconvulsive SE. An algorithm was then designed to aid nursing and medical staff in decision making about the type of SE and pharmacological intervention needed to stop prolonged or repetitive seizures occurring in patients undergoing video electroencephalogram (EEG) monitoring. A treatment algorithm for diagnosing and treating SE has clinical benefits in the practice setting of an inpatient comprehensive epilepsy program. Episodes of SE are more accurately classified and faster successful treatment of the episode occurs.


Impact of heat processing on the nutritional content of Gryllus bimaculatus (black cricket).
Insects are increasingly suggested as a potential novel solution to global nutrition challenges. However, limited research is available on the impact of processing methods on the nutritional content of edible insects. This trial examines the effect of heat processing on the nutritional profile of the black cricket, Gryllus bimaculatus. Adult black crickets were killed by freezing and then dried at either a low (45°C) or high (120°C) temperature followed by nutritional analysis of protein and micronutrient content. An additional set of samples was either freeze-dried or dried at 32, 45, 72 or 120°C followed by nutritional analysis of lipid content. Analysis showed that percentage protein content was significantly higher in crickets dried at 45°C, a difference of roughly 1% of the total weight. Similarly, calcium content was also significantly higher in crickets dried at 45°C, although no other measured micronutrients were affected. Additionally, the fatty acid content was significantly influenced by higher temperature processing. Freeze-drying black crickets conserved significantly more of the long-chain polyunsaturated fatty acids than drying at 120°C. Insects hold potential as a source of essential nutrients and fatty acids; however, consideration must be given to heat processing at high temperatures as this may affect the nutritional profile.


The neurobiology of human fear generalization: meta-analysis and working neural model.
Fear generalization to stimuli resembling a conditioned danger-cue (CS+) is a fundamental dynamic of classical fear-conditioning. Despite the ubiquity of fear generalization in human experience and its known pathogenic contribution to clinical anxiety, neural investigations of human generalization have only recently begun. The present work provides the first meta-analysis of this growing literature to delineate brain substrates of conditioned fear-generalization and formulate a working neural model. Included studies (K = 6, N = 176) reported whole-brain fMRI results and applied generalization-gradient methodology to identify brain activations that gradually strengthen (positive generalization) or weaken (negative generalization) as presented stimuli increase in CS+ resemblance. Positive generalization was instantiated in cingulo-opercular, frontoparietal, striatal-thalamic, and midbrain regions (locus coeruleus, periaqueductal grey, ventral tegmental area), while negative generalization was implemented in default-mode network nodes (ventromedial prefrontal cortex, hippocampus, middle temporal gyrus, angular gyrus) and amygdala. Findings are integrated within an updated neural account of generalization centering on the hippocampus, its modulation by locus coeruleus and basolateral amygdala, and the excitation of threat- or safety-related loci by the hippocampus.


Hospital prescribing and usage of hypnotics and anxiolytics.
In-patient prescribing and usage of hypnotic and anxiolytic drugs were surveyed in a teaching hospital for 4 to 6 weeks. Twenty-one percent of admissions were prescribed these drugs which were predominantly benzodiazepines. Few patients (1.6%) were discharged with such prescriptions and subsequent usage in the community was similar to that before admission to hospital (6.1% and 6.4% respectively). In-patient consumption increased with patient age and both prescriptions and consumption were greater in women than men.


Mustard baffle obstruction and leak - How successful are percutaneous interventions in adults?
Atrial switch operations for D-Transposition of the great arteries (D-TGA) were performed until the late 20th century. These patients have substantial rates of re-operation, particularly for baffle related complications. This study sought to analyze the efficacy of percutaneous transcatheter intervention (PTI) for baffle leak and/or stenosis in adult atrial switch patients. Adult patients with a prior atrial switch operation who underwent heart catheterization (2002-2014) at a tertiary adult congenital heart disease referral center were retrospectively analyzed. In 58 adults (30 ± 8 years, 75% men, 14% New York Heart Association (NYHA) functional class ≥2) who underwent 79 catheterizations, PTI was attempted in 50 (baffle leak (n = 10, 20%), stenosis (n = 27, 54%), or both (n = 13, 26%)). PTI was successful in 45 and 5 were referred for surgery due to complex anatomy. A total of 40 bare metal stents, 18 covered stents, 16 occlusion devices, 2 angioplasties, and 1 endovascular graft were deployed. In isolated stenosis, there was improvement in NYHA functional class after PTI (8 vs. 0 patients were NYHA FC > 2, p = 0.004), which was matched by improvement in maximal oxygen consumption on exercise testing (VO2) (25.1 ± 5.4 mL/kg/min vs. 27.9 ± 9 mL/kg/min, p = 0.03). There were no procedure-related deaths or emergent surgeries in this cohort. This single-center cohort is the largest reported series of adult atrial switch operation patients who have undergone PTI for baffle stenosis and/or leak. We demonstrate that PTI with an expert multi-disciplinary team is a safe and effective alternative to surgery in adult patients with an atrial switch operation.


Applying compositional data methodology to nutritional epidemiology.
The purpose of epidemiological studies of nutrition and disease is to investigate the effects of specific dietary components regardless of total energy intake, but this is sometimes hampered by the compositional nature of dietary data. Compositional data are those that measure parts of a whole, such as percentages or proportions, and particular methodologies have been developed to allow their statistical analysis and theoretical and practical applications in various sciences. This paper describes the use of a compositional data perspective for statistical analyses in the field of nutritional epidemiology. The approach is based on isometric log-ratio transformation and has been previously proposed for the construction of regression models using compositional explanatory variables. The new isometric log-ratio variables allow full inferences about each element of dietary composition and adjustment by total energy intake. Using data from an Italian population-based study, logistic regression models were fitted to evaluate the effects of the intake of macronutrients (proteins, fats and carbohydrates) on the odds of having metabolic syndrome in middle-aged subjects.


An integrated bioconversion process for production of L-lactic acid from starchy potato feedstocks.
The potential market for lactic acid as the feedstock for biodegradable polymers, oxygenated chemicals, and specialty chemicals is significant. L-lactic acid is often the desired enantiomer for such applications. However, stereospecific lactobacilli do not metabolize starch efficiently. In this work, Argonne researchers have developed a process to convert starchy feedstocks into L-lactic acid. The processing steps include starch recovery, continuous liquefaction, and simultaneous saccharification and fermentation. Over 100 g/L of lactic acid was produced in less than 48 h. The optical purity of the product was greater than 95%. This process has potential economical advantages over the conventional process.


Dietary Potential Renal Acid Load Is Positively Associated with Serum Uric Acid and Odds of Hyperuricemia in the German Adult Population.
Initial interventional data indicate that a reduction in dietary acid load (e.g., by an increased consumption of alkalizing fruit and vegetables) can increase renal uric acid excretion and decrease serum uric acid (SUA). Against this background, we examined the association between dietary potential renal acid load (PRAL) and SUA in a representative population sample. Cross-sectional analyses were performed in 6894 participants (aged 18-79 y) of the German Health Interview and Examination Survey for Adults (DEGS1). Dietary intake was assessed with a food-frequency questionnaire. Nutritive acid load and the intake of uric acid equivalents (UAEs) were characterized by assigning PRAL and UAE values to reported food consumption. In multiple linear regression models, the associations of PRAL, UAEs, and relevant food groups with SUA were analyzed. Multiple logistic regressions were used to calculate ORs for hyperuricemia comparing lower and upper tertiles of the predictors. After adjustment for relevant confounders, PRAL (P = 0.003), alcohol (P < 0.0001), and UAE (P = 0.03) intakes were positively associated with SUA, whereas the intake of dairy products and fruit and vegetables was inversely associated (both P < 0.0001). Subgroup analyses among participants without interacting medication use confirmed these results. In addition, participants with lower PRAL had lower odds for hyperuricemia (OR: 0.60; 95% CI: 0.43, 0.83). Apart from observing known dietary influences on SUA, we found in this population-based, cross-sectional study in adults that low PRAL may represent a potentially SUA-reducing dietary pattern. This highlights dietary alkalization as a possible nonpharmacologic option to influence elevated SUA concentrations.


Caffeic and ferulic acid as blockers of nitrosamine formation.
Caffeic acid and ferulic acid, which are naturally occurring phenols present in a wide variety of plants, were examined for their ability to react with nitrite in vitro and to inhibit nitrosamine formation in vivo. Their activities were compared with other phenols (butylated hydroxyanisole and Trolox) and with a non-phenolic polyhydroxylated compound, glycerol guaiacolate. In simulated gastric fluid, caffeic acid and ferulic acid reacted rapidly and completely with an equimolar quantity of sodium nitrite. In rats receiving aminopyrine and nitrite, caffeic acid and ferulic acid blocked the elevation of serum N-nitrosodimethylamine (NDMA) levels and the serum glutamic pyruvic transaminase levels associated with hepatotoxicity. Neither phenol had any effect on serum levels of NDMA in rats treated with NDMA. In both the in vitro (reaction with nitrite) and in vivo (inhibition of hepatotoxicity) systems, caffeic acid was more effective than ferulic acid. Butylated hydroxyanisole and Trolox were partially effective, and glycerol guaiacolate was inactive. The results of this study suggest that dietary caffeic acid and ferulic acid may play a role in the body's defense against carcinogenesis by inhibiting the formation of N-nitroso compounds.


Longitudinal gut microbiota composition of South African and Nigerian infants in relation to tetanus vaccine responses.
Infants who are exposed to HIV but uninfected (iHEU) have higher risk of infectious morbidity than infants who are HIV-unexposed and uninfected (iHUU), possibly due to altered immunity. As infant gut microbiota may influence immune development, we evaluated the effects of HIV exposure on infant gut microbiota and its association with tetanus toxoid (TT) vaccine responses. We evaluated gut microbiota by 16S rRNA gene sequencing in 278 South African and Nigerian infants during the first and at 15 weeks of life and measured antibodies against TT vaccine by enzyme-linked immunosorbent assay (ELISA) at matched time points. Infant gut microbiota and its succession were more strongly influenced by geographical location and age than by HIV exposure. Microbiota of Nigerian infants drastically changed over 15 weeks, becoming dominated by Bifidobacterium longum subspecies infantis. This change was not observed among EBF South African infants. Lasso regression suggested that HIV exposure and gut microbiota were independently associated with TT vaccine responses at week 15, and that high passive antibody levels may mitigate these effects. In two African cohorts, HIV exposure minimally altered the infant gut microbiota compared to age and country, but both specific gut microbes and HIV exposure independently predicted humoral vaccine responses.


Paternal high protein diet modulates body composition, insulin sensitivity, epigenetics, and gut microbiota intergenerationally in rats.
Mounting evidence demonstrates that paternal diet programs offspring metabolism. However, the contribution of a pre-conception paternal high protein (HP) diet to offspring metabolism, gut microbiota, and epigenetic changes remains unclear. Here we show that paternal HP intake in Sprague Dawley rats programs protective metabolic outcomes in offspring. Compared to paternal high fat/sucrose (HF/S), HP diet improved body composition and insulin sensitivity and improved circulating satiety hormones and cecal short-chain fatty acids compared to HF/S and control diet (P < .05). Further, using 16S rRNA gene sequencing to assess gut microbial composition, we observed increased alpha diversity, distinct bacterial clustering, and increased abundance of Bifidobacterium, Akkermansia, Bacteroides, and Marvinbryantia in HP fathers and/or male and female adult offspring. At the epigenetic level, DNMT1and 3b expression was altered intergenerationally. Our study identifies paternal HP diet as a modulator of gut microbial composition, epigenetic markers, and metabolic function intergenerationally.


Minimally invasive cardiac surgery by the port-access method.
Recently, minimally invasive surgery has come to be an important theory in cardiac surgery, the goal of which is shortening of hospital stay, earlier recovery of employment, and cosmetics. In this paper, we will describe our experience with port-access cardiac surgery conducted under the support of our new technology. This study assesses the quality of cardiac surgery performed by the port-access method. The author developed a direct endoaortic clamp balloon (Yozu balloon). This balloon is a triple-lumen balloon catheter of 3.6 mm in outer diameter and 40 cm in full length. The balloon is inserted directly into the ascending aorta. Injection of cardioplegic solution and aortic vent can be conducted. Also, we introduce a modified Cosgrove flex clamp to apply in small-incision surgery, aiming at a less invasive procedure. The modified point is that the original, united Cosgrove flex clamp can be divided into the handle part equipped with a ratchet, and the bellows part equipped with a clamp jaw. By this modification, it became possible to apply the Cosgrove flex clamp transthoracically; that is, it became possible to conduct aortic clamping safely and securely through this small port of 8 mm in diameter. Port-access cardiac surgery is one of the developing and promising methods of cardiac operation. In view of future technological progress, we can expect the gradual but wide popularization of this method.


Lyme disease in children.
Neurologic manifestations of Lyme disease are common in children, among whom the incidence of Lyme disease is higher than among adults. Cranioneuropathies, in particular palsy of the facial nerve, occur in approximately 3-5% of children with Lyme disease, followed in frequency by meningitis (1% of symptomatic children). Children with only non-specific symptoms such as headache, arthralgia or fatigue commonly are misdiagnosed as having Lyme disease. Although such non-specific symptoms often accompany more specific signs and symptoms (e.g., erythema migrans, arthritis) in children with Lyme disease, very rarely are non-specific symptoms the sole manifestation of Lyme disease. A number of carefully conducted follow-up studies have indicated that the prognosis is excellent for children with Lyme disease who have been treated with standard antimicrobial regimens.


Variations in binding affinities of the peripheral nicotinic acetylcholine receptor can be attributed to endogenous acetylcholine.
Equilibrium binding studies performed with fresh membrane fragments from Torpedo marmorata reveal a low affinity for [3H]acetylcholine with an equilibrium dissociation constant in the micromolar range and no indication of cooperative interactions. The low binding affinity is an artifact caused by the presence of endogenous acetylcholine and is not related to the active conformation of the receptor. Endogenous acetylcholine is identified by its interaction with acetylcholine esterase and choline kinase. It is present in presynaptic vesicles as shown in electron micrographs. Leakage of these synaptosomes is of the order of 300 pmol acetylcholine per g tissue as determined by means of binding studies performed with [3H]acetylcholine. In the absence of endogenous acetylcholine, equilibrium binding studies show a high affinity for [3H]acetylcholine and a slight cooperativity of sites (K1D = 30nM; K2D = 10nM). The addition of detergents, local anesthetics or alcohols to a further increase in affinity and to a decrease in cooperativity (K1D = 11nM; K2D = 5nM). No low-affinity binding can be detected in the micromolar range.


An experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated piglets.
The objectives of the study were to validate a model of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in ventilated piglets and to study the time-course of biological markers and histopathological changes. 12 piglets were intubated and inoculated with 15 mL of a suspension of 10(6) colony forming units of MRSA in every lobe through the bronchoscope channel. The piglets were ventilated for 12 h (n = 6) and 24 h (n = 6). Clinical parameters were assessed every 6 h and pro-inflammatory cytokines were measured in serum and in bronchoalveolar lavage (BAL) at baseline and sacrifice. Histopathology of each lobe and cultures from blood, lungs and BAL were performed. Animals developed histopathological evidence of pneumonia at necropsy. At 12 h, pneumonia was present in all animals and was severe pneumonia at 24 h. Microbiological studies confirmed the presence of MRSA. A significant increase in interleukin (IL)-6, IL-8 and tumour necrosis factor-α values was seen in BAL at 24 h and IL-6 at 12 h. In serum, only IL-6 levels had increased significantly at 24 h. In ventilated piglets, bronchoscopic inoculation of MRSA induces pneumonia at 12 h and severe pneumonia at 24 h. This severity was associated with a corresponding increase in systemic and local inflammatory response.


Catheter ablation of focal atrial tachycardia originating from a donor heart after bicaval orthotopic heart transplantation guided by a noncontact mapping system.
A 19-year-old man who underwent bicaval orthotopic heart transplantation for idiopathic dilated cardiomyopathy complained of palpitations 2 weeks after the heart transplantation. An ECG revealed paroxysmal atrial tachycardia (AT) with a cycle length of 260 ms and the P wave morphology of the AT was similar to that during sinus rhythm. Echocardiography showed normal contraction. No rejection, vasculopathy, or infection was observed. An electrophysiologic study and catheter ablation guided by a noncontact mapping system were performed due to drug refractory AT. The AT was induced spontaneously by isoproterenol infusion. The activation sequence of the AT exhibited a focal pattern, and the breakout site of the AT into the donor right atrium was just 12 mm below the breakout site of the donor sinoatrial node. Radiofrequency catheter ablation eliminated this AT and resulted in an improvement in the symptoms.


[Antitumor effects of newly synthesized analogues of platinum (NK121) and bleomycin (NK313) in nude mice implanted human tumor].
In order to exploit the optimal administration schedules of newly synthesized analogues of cisplatin (NK121) and bleomycin (NK313), antitumor effects of three different injection schedules, namely (A) an injection every fourth day for 3 times in 9 days, (B) once daily injection for 9 days, and (C) continuous infusion for 5 days, were examined in nude mice bearing human squamous cell carcinoma. The tumor growth delay was employed as an experimental endpoint. Antitumor effects of both analogues showed schedule dependencies showing the highest effect with schedule (A) of NK121 and schedule (C) of NK313, respectively. In the combination chemotherapy of NK121 with NK313, the highest antitumor effect was observed when mice were given NK121 by schedule (A) followed by NK313 by schedule(C). This combination sequence also was less toxic with respect to the change of the body weight, while simultaneous treatment was with weak clinical significance because of its low antitumor activity and severe toxicity.


Worldwide emergence of multiple clades of enterovirus 68.
Human enterovirus 68 (EV-D68) is a historically rarely reported virus linked with respiratory disease. In the past 3 years, a large increase in respiratory disease associated with EV-D68 has been reported, with documented outbreaks in North America, Europe and Asia. In several outbreaks, genetic differences were identified among the circulating strains, indicating the presence of multiple clades. In this report, we analyse archived and novel EV-D68 strains from Africa and the USA, obtained from patients with respiratory illness. Phylogenetic analysis of all EV-D68 sequences indicates that, over the past two decades, multiple clades of the virus have emerged and spread rapidly worldwide. All clades appear to be currently circulating and contributing to respiratory disease.


Ionic liquid for in situ Vis/NIR and Raman spectroelectrochemistry: Doping of carbon nanostructures.
1-butyl-3-methylimidazolium tetrafluoroborate (an ionic liquid) is an advantageous electrolyte for the study of charge-transfer reactions at single-walled carbon nanotubes (SWCNTs) and fullerene peapods (C60@SWCNT). Compared to traditional electrolyte solutions, this medium offers a broader window of electrochemical potentials to be applied, and favorable optical properties for in situ Vis/NIR and Raman spectroelectrochemistry of nano-carbon species. The electrochemistry of both nanotubes and peapods is dominated by their capacitive double-layer charging. Vis/NIR spectroelectrochemistry confirms the charging-induced bleaching of transitions between Van Hove singularities. At high positive potentials, new optical transitions were activated in partly filled valence band. The bleaching of optical transitions is mirrored by the quenching of resonance Raman scattering in the region of tube-related modes. The Raman frequency of the tangential displacement mode of SWCNT shifts to blue upon both anodic and cathodic charging in the ionic liquid. The Raman modes of intratubular C60 exhibit a considerable intensity increase upon anodic doping of peapods.


Guanabenz for adolescent hypertension.
Guanabenz, a centrally acting antihypertensive agent that acts through stimulation of central alpha-adrenergic receptors, appears to produce neither sodium retention nor clinically significant renal, cardiac, hepatic, or metabolic abnormalities. This 2-month open, uncontrolled dose-finding and short-term safety and efficacy trial was conducted in 11 male outpatients (12 to 21 years old) to establish the potential use of guanabenz in treating children with hypertension. Doses of 3 to 12 mg/day (0.07 to 0.17 mg/kg/day) given twice daily effectively lowered blood pressure in all patients. Mean supine blood pressure was significantly (P less than 0.05) reduced from 135/91/81 mmHg (phase I/IV/V) at baseline to 124/80/66 mmHg after approximately 2 months of treatment. Mean supine pulse rate also was significantly (P less than 0.05) reduced (10 beats/minute), while standing pulse rate and body weight were unaffected by guanabenz therapy. Adverse effects, the most common being headache, dry mouth, and drowsiness, were generally mild and did not interfere with continued therapy. No abnormal findings were noted in laboratory test results or physical examinations. These preliminary results suggest that guanabenz is safe and effective for the treatment of childhood hypertension.


Use of two-dimensional electrophoretic protein maps in studies of schizophrenia.
High resolution two-dimensional electrophoresis (2DE) and silver staining have provided a technology capable of mapping large numbers of proteins from tissues and body fluids. Further identification of individual proteins that have been visualized by 2DE includes their characterization by immunodetection methods and by obtaining amino acid sequences from which antibody and synthetic oligonucleotide probes can be synthesized. As many as 3,500 individual proteins may be observed on a single electrophoretogram. This capacity to observe gene products permits the scanning of as many as 3.5 megabases of the protein coding regions of the genome for mutational events on each gel, and may also provide evidence concerning abnormal rates of protein synthesis or degradation, posttranslational modifications, and the presence of gene products of exogenous origin. The application of this technology has revealed a pair of abnormal cerebrospinal fluid (CSF) proteins (40KD) in one-third of schizophrenic patients screened. These abnormal proteins have never been observed in CSF from normal controls. However, they have been detected in some diseases of the central nervous system that may be of viral origin. Structural studies on these proteins should provide evidence of their origin, while ongoing studies of brain proteins may provide additional clues about this disease.


Systems for physical health care for mental health patients in the community: different approaches to improve patient care and safety in an Early Intervention in Psychosis Service.
Patients with mental illnesses have a high rate of physical comorbidity, and specifically, those with psychosis are at an increased risk of cardiometabolic disease and shortened lifespans, due to medication, lifestyle and illness factors. There are recognised challenges with physical health care in this group. At baseline, no patients on the Bath and North East Somerset Early Intervention in Psychosis caseload had a fully completed physical health assessment. Our aim was to offer a physical health check, blood tests, and ECG for all patients, trialling four phases of interventions. The four phases were (1) increased awareness, education and data collection tools; (2) mobile physical health clinics; (3) letters sent to patients and GPs to request health checks be conducted, (4) a combination of the above approaches, as well as regular caseload reviews and prompts to professionals. At the time of our study (2015-16), many of the above parameters were also incentivised nationally by Commissioning for Quality and Innovation (CQUIN) payments. The mobile physical health clinic offered patient choice of home visits or clinic checks, to increase engagement and provide flexible care. The most successful approach overall was the combination approach, resulting in 48% of all patients having fully completed physical health checks, bloods and ECGs. The mobile clinic resulted in physical health checks completion rates of 60%, and blood tests in 65-70%. 92% of patients undertook ECG's, following letter requests to GPs and patients. Combining mobile physical health clinics, GP letters, financial incentives and managerial engagement produced much improved results, but was very time consuming, and in our case was inefficient due to using multiple professionals. We recommend embedding such approaches within the team, using sustainable systems, and would encourage teams to trial dedicated trained clinicians to establish sustainable systems to improve the physical health care of this vulnerable group.


Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis: a randomized assessor-blind controlled trial.
To determine the efficacy and safety of imiquimod in combination with meglumine antimoniate in treating cutaneous leishmaniasis. Prospective, randomized, assessor-blind, parallel-design, placebo-controlled trial. Two primary care health clinics. One hundred nineteen patients (59 patients in the imiquimod group and 60 in the placebo group) were included in the study. Patients were randomly assigned to receive a combined 4-week course of imiquimod or placebo with meglumine antimoniate treatment (20 mg/kg of pentavalent antimony daily for 2 weeks) in an endemic area of Leishmania tropica. The primary end point was clinical cure, defined as more than 75% reduction in the size of lesions compared with baseline at week 8. At the end of the 4-week treatment period, clinical cure was similar in both groups (11 patients [18.6%] in the imiquimod-treated group vs 18 patients [30.0%] in the placebo group) (P = .15). Four weeks after the end of treatment, 26 patients (44.1%) and 29 patients (48.3%) in the imiquimod-treated and placebo groups, respectively, were cured (P = .64). Pruritus and burning sensation were reported by 3 patients treated with imiquimod and by no patients treated with placebo. This study showed no beneficial effect of combining a 4-week course of treatment with 5% imiquimod cream and a standard course of treatment with meglumine antimoniate in patients with cutaneous leishmaniasis in an endemic area of L tropica. isrctn.org Identifier:ISRCTN77659407 and Cochrane Skin Group Identifier: CSG Trial No. 32.


A Regularized Deep Learning Approach for Clinical Risk Prediction of Acute Coronary Syndrome Using Electronic Health Records.
Acute coronary syndrome (ACS), as a common and severe cardiovascular disease, is a leading cause of death and the principal cause of serious long-term disability globally. Clinical risk prediction of ACS is important for early intervention and treatment. Existing ACS risk scoring models are based mainly on a small set of hand-picked risk factors and often dichotomize predictive variables to simplify the score calculation. This study develops a regularized stacked denoising autoencoder (SDAE) model to stratify clinical risks of ACS patients from a large volume of electronic health records (EHR). To capture characteristics of patients at similar risk levels, and preserve the discriminating information across different risk levels, two constraints are added on SDAE to make the reconstructed feature representations contain more risk information of patients, which contribute to a better clinical risk prediction result. We validate our approach on a real clinical dataset consisting of 3464 ACS patient samples. The performance of our approach for predicting ACS risk remains robust and reaches 0.868 and 0.73 in terms of both AUC and accuracy, respectively. The obtained results show that the proposed approach achieves a competitive performance compared to state-of-the-art models in dealing with the clinical risk prediction problem. In addition, our approach can extract informative risk factors of ACS via a reconstructive learning strategy. Some of these extracted risk factors are not only consistent with existing medical domain knowledge, but also contain suggestive hypotheses that could be validated by further investigations in the medical domain.


Modeling a secular trend by Monte Carlo simulation of height biased migration in a spatial network.
Background: In a recent Monte Carlo simulation, the clustering of body height of Swiss military conscripts within a spatial network with characteristic features of the natural Swiss geography was investigated. In this study I examined the effect of migration of tall individuals into network hubs on the dynamics of body height within the whole spatial network. The aim of this study was to simulate height trends. Material and methods: Three networks were used for modeling, a regular rectangular fishing net like network, a real world example based on the geographic map of Switzerland, and a random network. All networks contained between 144 and 148 districts and between 265-307 road connections. Around 100,000 agents were initially released with average height of 170 cm, and height standard deviation of 6.5 cm. The simulation was started with the a priori assumption that height variation within a district is limited and also depends on height of neighboring districts (community effect on height). In addition to a neighborhood influence factor, which simulates a community effect, body height dependent migration of conscripts between adjacent districts in each Monte Carlo simulation was used to re-calculate next generation body heights. In order to determine the direction of migration for taller individuals, various centrality measures for the evaluation of district importance within the spatial network were applied. Taller individuals were favored to migrate more into network hubs, backward migration using the same number of individuals was random, not biased towards body height. Network hubs were defined by the importance of a district within the spatial network. The importance of a district was evaluated by various centrality measures. In the null model there were no road connections, height information could not be delivered between the districts. Results: Due to the favored migration of tall individuals into network hubs, average body height of the hubs, and later, of the whole network increased by up to 0.1 cm per iteration depending on the network model. The general increase in height within the network depended on connectedness and on the amount of height information that was exchanged between neighboring districts. If higher amounts of neighborhood height information were exchanged, the general increase in height within the network was large (strong secular trend). The trend in the homogeneous fishnet like network was lowest, the trend in the random network was highest. Yet, some network properties, such as the heteroscedasticity and autocorrelations of the migration simulation models differed greatly from the natural features observed in Swiss military conscript networks. Autocorrelations of district heights for instance, were much higher in the migration models. Conclusion: This study confirmed that secular height trends can be modeled by preferred migration of tall individuals into network hubs. However, basic network properties of the migration simulation models differed greatly from the natural features observed in Swiss military conscripts. Similar network-based data from other countries should be explored to better investigate height trends with Monte Carlo migration approach.


SLE Antibody-Secreting Cells Are Characterized by Enhanced Peripheral Maturation and Survival Programs.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibodies, some of which are present in high titers in a sustained, B cell-independent fashion consistent with their generation from long-lived plasma cells (LLPC). Active SLE displays high numbers of circulating antibody-secreting cells (ASC). Understanding the mechanisms of generation and survival of SLE ASC would contribute important insight into disease pathogenesis and novel targeted therapies. We studied the properties of SLE ASC through a systematic analysis of their phenotypic, molecular, structural, and functional features. Our results indicate that in active SLE, relative to healthy post-immunization responses, blood ASC contain a much larger fraction of newly generated mature CD19- CD138+ ASC similar to bone marrow (BM) LLPC. SLE ASC were characterized by morphological and structural features of premature maturation. Additionally, SLE ASC express high levels of CXCR4 and CD138, and molecular programs consistent with increased longevity based on pro-survival and attenuated pro-apoptotic pathways. Notably, SLE ASC demonstrate autocrine production of APRIL and IL-10 and experience prolonged in vitro survival. Combined, our findings indicate that SLE ASC are endowed with enhanced peripheral maturation, survival and BM homing potential suggesting that these features likely underlie BM expansion of autoreactive PC.


ZnT-8, a pancreatic beta-cell-specific zinc transporter.
The zinc content in the pancreatic beta cell is among the highest of the body. Zinc appears to be an important metal for insulin-secreting cells as insulin is stored inside secretory vesicles as a solid hexamer bound with two Zn(2+) ions per hexamer. Zinc is also an important component of insulin secretion mechanisms and is likely to modulate the function of neighbouring cells via paracrine/autocrine interactions. Therefore beta cells undoubtedly need very efficient and specialized transporters to accumulate sufficient amounts of zinc in secretion vesicles. We report here the discovery and the characteristics of a new zinc transporter, ZnT-8, belonging to the CDF (Cation Diffusion Facilitator) family and expressed only in pancreatic beta cells. This transporter, localized in secretion vesicles membrane, facilitates the accumulation of zinc from the cytoplasm into intracellular insulin-containing vesicles and is a major component for providing zinc to insulin maturation and/or storage processes in insulin-secreting pancreatic beta cells. We discovered mammalian orthologs (rat, mouse, chimpanzee, and dog) and found these ZnT-8 proteins very similar (98% conserved amino acids) to human ZnT-8, indicating a high conservation during evolution.


Recent Aspects of Osmotic Pump Systems: Functionalization, Clinical use and Advanced Imaging Technology.
Osmotic pump drug delivery systems are one of the most promising and widely developed systems. They are based on the principle of osmosis and are characterized by a zero-order release pattern independent of the physicochemical properties of the drug involved and some physiological factors. In the past 30 years, a series of difficulties, such as the very wide solubility range of different drugs, have been resolved accompanied by the development of various types of osmotic pumps. Furthermore, more advanced designs have been proposed according to practical requirements. We started a systematic references collection on osmotic pump systems through different available databases. Then these information were analyzed and divided according to different subjects. Finally, we made clear our thought and begun to write it in a logical way. This review mainly concentrates on five kinds of functional osmotic pumps including technology combined, targeted, chronotherapy- based, ascending and compound osmotic pumps, involving ways to improve bioavailability and reduce side effects. Special attention is paid to the application of advanced imaging technologies to study osmotic pumps including the coating process, processing steps, polymer hydration and changes in the internal structure. Present-day osmotic pumps not only produce a constant release, but also have the ability to produce adjustable release according to practical requirements. Hence, technology combined, targeted, chronotherapy-based, ascending and compound osmotic pumps are a positive development. These latest advances offer various advantages compared with the classic osmotic pump, and enable them to meet the new needs for clinical use with fewer side effects and improved safety. In addition, following the improvements in the versatility and complexity of the novel osmotic pump system, conventional assessing parameters may fail to meet the increasing demand for information. Hence, novel imaging and monitoring technologies have been employed to monitor osmotic pumps from the coating process, processing steps, and polymer hydration to the changes in polymeric internal structure, which are associated with the different performance offered by the in vivo action of similar products.


Development and Scale-up of the Rapid Synthesis of Triphenyl Phosphites in Continuous Flow.
A novel method for the synthesis of triphenyl phosphite and its derivatives has been developed in continuous flow. With a total residence time of 20 s, the target product was prepared in a microreactor, and the reaction time was significantly shortened compared with standard single batch reaction conditions. In addition, the reaction of various substrates gave the corresponding products in good to excellent yields under optimized conditions. The reactants could be employed in a stoichiometric ratio, making the reaction more efficient, economical, and environmentally friendly. In addition, scale-up apparatus was designed and assembled, and the kilogram-scale production (up to 18.4 kg/h) of tris(2,4-di-tert-butylphenyl) phosphite was achieved in 88% yield.


Malignant potential of epithelioid angiomyolipomas of the liver: A case report and comprehensive review of the literature.
Hepatic epithelioid angiomyolipoma (HEAML) is a rare mesenchymal tumor that has been reported to have malignant potential. We herein describe a rare case of atypical HEAML. A 43-year-old Caucasian male patient visited his general practitioner due to a productive cough persisting for >2 months. During evaluation with several imaging tests, a chest computed tomography (CT) incidentally revealed a well-demarcated lesion in the caudate lobe of the liver, sized 7 cm. An abdominal magnetic resonance imaging examination confirmed the findings of the CT. The possibility of hepatocellular carcinoma at that time could not be excluded. Due to inconclusive cross-sectional imaging, the patient underwent left hepatectomy with additional resection of segment I. The patient's postoperative course was uneventful. A diagnosis of 'atypical' HEAML was established in the present case. The majority of HEAMLs are considered to be benign, although there are several reported cases exhibiting malignant behavior, such as tumor growth, presence of atypical cells, recurrence after surgical resection, metastasis and invasive growth into the liver parenchyma and alongside the vessels. From 2000 onwards, 19 cases of malignant hepatic AML have been reported. Malignant transformation is considered to occur mostly in the epithelioid subtype. To that end, when epithelioid or atypical characteristics are identified on preoperative biopsy, resection is indicated due to the high probability of malignancy.


Homophobic Bullying and Cyberbullying: Study of a Silenced Problem.
Bullying and cyberbullying have been studied extensively. In lesbian, gay, bisexual, and questioning (LGBQ) students, these phenomena seem to be overrepresented so that, although they share some common elements, homophobic bullying and cyberbullying could be considered as specific phenomena. This study analyzed homophobic bullying and cyberbullying, with the participation of 533 Spanish secondary school students aged from 12 to 20 (M = 14.9, SD = 1.7). The results showed that students identified as non-heterosexual experienced a higher level of being targeted with bullying and cyberbullying, almost one half of them declaring that they had been victimized and more than 20% cybervictimized. Many stated they had suffered both kinds of harassment. In addition, the prevalence of all kinds of bullying was higher among non-heterosexual students. Regression analyses showed that sexual orientation could be considered a risk factor for suffering these aggressions. We discuss results in relation to previous research and look at their practical implications.


[Epidemiological study on the trend of accidental deaths among children under five in Guangzhou, 2001 - 2010].
To study the trend of accidental death among children under 5 years of age. A survey on accidental death among children was performed in Guangzhou to compare the data from the national monitoring program on the deaths under five in the same period during 2001 - 2010. Data on mortality and causes of injures were adjusted by missing reports. Mortality rates on injuries were decreasing annually from 2001 to 2010. Comparing with 2001, the magnitude of the drop in mortality among the 0, 1 - 4 and under 5 year groups were 72.02%, 77.17% and 74.66% respectively, with statistically significant differences (P = 0.000). During the 10 years of observation, data showed a dropping trend (P = 0.000) of the mortalities on drowning, traffic accident, suffocation and falling, especially on drowning and suffocation. The main causes of death were suffocation in the 0 year group, drowning in the 1-2-year group, traffic accident and poisoning in the 3-year group, traffic accident and falling in the 4-year group. The accidental deaths happened in 'C area' which including Huadu, Conghua, Zengcheng, Panyu and Nansha, with the total proportion of accidental death in Guangzhou as 75.69%. The mortality of accidental deaths among children under 5 years of age in Guangzhou had been decreasing during 2001 - 2010, mainly owing to the practice of intervention programs on drowning and suffocation, suggesting the necessity of integrating the health education programs on accidental injury with the healthcare management system in children in the country, focusing on the suburban and county levels where economy was relatively undeveloped or with more floating population.