Duration of carriage of carbapenem-resistant Enterobacteriaceae following hospital discharge.
Hospitalized carriers of carbapenem-resistant Enterobacteriaceae (CRE) are cohorted under contact precautions, including in the days between rehospitalization and surveillance culture results. This study investigates duration of CRE carriage to define populations requiring precautions upon readmission. Patients with CRE-positive culture during 2009-2010 were followed up by rectal swab cultures taken retrospectively and prospectively for the study or as part of clinical follow-up. One hundred thirty-seven patients met the inclusion criteria, with follow-up cultures obtained from 97. Mean time to CRE negativity was 387 days (95% confidence interval: 312-463). Seventy-eight percent of patients (64/82) had positive culture at 3 months, 65% (38/58) at 6 months, and 39% (12/30) at 1 year. Duration of carriage was affected by repeat hospitalization (P = .001) and clinical, as opposed to surveillance, culture (P = .002). CRE carriers from a previous hospitalization have a lower probability of CRE carriage upon readmission if the index specimen was a surveillance culture and 1 year passed without further hospitalization. Multiple hospitalizations and CRE disease extend duration of carriage. This study better defines patients requiring cohorting and isolation, thus limiting spread of CRE and allowing for improved allocation of infection control measures.


Dasatinib (BMS-354825) is active in Philadelphia chromosome-positive chronic myelogenous leukemia after imatinib and nilotinib (AMN107) therapy failure.
Developing strategies to counteract imatinib resistance constitutes a challenge in chronic myelogenous leukemia (CML). Therapy with the tyrosine kinase inhibitors nilotinib (AMN107) and dasatinib (BMS-354825) has produced high rates of hematologic and cytogenetic response. Src kinase activation has been linked to Bcr-Abl-mediated leukemogenesis and CML progression. In addition to binding Abl kinase with less stringent conformational requirements than imatinib, dasatinib is a potent Src kinase inhibitor. In the current study, we report on 23 patients with CML (19 of them in accelerated or blastic phases) treated with dasatinib after treatment failure with both imatinib and nilotinib. More than half (13; 57%) of 23 patients responded to dasatinib: 10 (43%) had a complete hematologic response (CHR), including 7 (30%) who had a cytogenetic response (2 complete, 4 partial, and 1 minor). These results suggest that dasatinib may be active in some patients after failure with both imatinib and nilotinib.


Familial childhood systemic lupus erythematosus: report of 2 cases.
Systemic lupus erythematosus is a multisystem organ inflammation due to damage of cells and tissues by pathogenic auto-antibodies and immune complexes. The most important factor for the causation of familial systemic lupus erythematosus is genetic on which environmental factor usually coexists. Two brothers of 7 and 3 years of age having childhood systemic lupus erythematosus are reported here because of low incidence and familial occurrence. Both the children fulfilled the American Rheumatology Association (ARA) criterion of systemic lupus erythematosus though anti-dsDNA was negative in both and antinuclear factor was positive only in the younger child. Systemic lupus erythematosus begins in childhood in 20% of adult patients and usually after the age of 8 years but here onset was even at an earlier age. The treatment of the both the siblings included administration of steroids and cyclophosphamide.


Reconstitution of a protein disulfide catalytic system.
Disulfide bonds are important for the structure and stability of many proteins. In prokaryotes their formation is catalyzed by the Dsb proteins. The DsbA protein acts as a direct donor of disulfides to newly synthesized periplasmic proteins. Genetic evidence suggests that a second protein called DsbB acts to specifically reoxidize DsbA. Here we demonstrate the direct reoxidation of DsbA by DsbB. We have developed a fluorescence assay that allows us to directly follow the reoxidation of DsbA. We show that membranes containing catalytic amounts of DsbB can rapidly reoxidize DsbA to completion. The reaction strongly depends on the presence of oxygen, implying that oxygen serves as the final electron acceptor for this disulfide bond formation reaction. Membranes from a dsbB null mutant display no DsbA reoxidation activity. The ability of DsbB to reoxidize DsbA fits Michaelis-Menten behavior with DsbA acting as a high affinity substrate for DsbB with a Km = 10 microM. The in vitro reconstitution described here is the first biochemical analysis of DsbB and allows us to study the major pathway of disulfide bond formation in Escherichia coli.


A Sensor Image Dehazing Algorithm Based on Feature Learning.
To solve the problems of color distortion and structure blurring in images acquired by sensors during bad weather, an image dehazing algorithm based on feature learning is put forward to improve the quality of sensor images. First, we extracted the multiscale structure features of the haze images by sparse coding and the various haze-related color features simultaneously. Then, the generative adversarial network (GAN) was used for sample training to explore the mapping relationship between different features and the scene transmission. Finally, the final haze-free image was obtained according to the degradation model. Experimental results show that the method has obvious advantages in its detail recovery and color retention. In addition, it effectively improves the quality of sensor images.


Diorganotin(IV) derivatives of N-methyl p-fluorobenzo-hydroxamic acid: preparation, spectral characterization, X-ray diffraction studies and antitumor activity.
Three diorganotin(IV) complexes of the general formula R2Sn[RcC(O)N(RN)O] (Rc = aryl, RN = Alkyl) have been synthesized by refluxing in toluene the corresponding diorganotin(IV) oxides with the free ligand N-methyl p-fluorobenzohydroxamic acid, using a Dean and Stark water separator. The ligand was derived from the reaction of the corresponding p-fluorobenzoyl chloride and N-methylhydroxylamine hydrochloride in the presence of sodium hydrogen carbonate. The isolated free ligand and its respective diorganotin compounds have been characterized by elemental analysis, IR and 1H-, 13C-, 119Sn-NMR spectroscopies. The crystal structures of the diorganotin complexes have been confirmed by single crystal X-ray diffraction methods. The investigations carried out on the diorganotin(IV) complexes of N-methyl p-fluorobenzohydroxamic acid confirmed a 1:2 stoichiometry. The complex formation took place through the O,O-coordination via the carbonyl oxygen and subsequent deprotonated hydroxyl group to the tin atom. The crystal structures of three diorganotin complexes were determined and were found to adopt six coordination geometries at the tin centre with coordination to two ligand moieties.


Use of health care services in seasonal affective disorder.
Little is known about the presentation and management of seasonal affective disorder (SAD) in primary care. To determine the use of health care services by people suffering from SAD. Following a screening of patients consulting in primary care, 123 were identified as suffering from SAD. Each was age- and gender-matched with two primary care consulters with minimal seasonal morbidity, yielding 246 non-seasonal controls. From primary care records, health care usage over a 5-year period was established. Patients with SAD consulted in primary care significantly more often than controls and presented with a wider variety of symptoms. They received more prescriptions, underwent more investigations and had more referrals to secondary care. Patients with SAD are heavy users of health care services. This may reflect the condition itself, its comorbidity or factors related to the personality or help-seeking behaviour of sufferers.


Testicular steroidogenesis in the testicular feminized (Tfm) mouse: loss of 17 alpha-hydroxylase activity.
Testicular feminized (Tfm) mice are totally insensitive to androgen and may be used to study the role of the androgen receptor in normal development and function. We have examined testicular and Leydig cell steroidogenesis in Tfm mice. Serum bioactive LH was high in Tfm mice but serum testosterone was low and this was associated with a severe reduction in testicular testosterone production in vitro. Examination of [3H]pregnenolone metabolism by testes of Tfm mice indicated that progesterone, rather than testosterone, was the major steroid produced. Leydig cells were isolated from normal and Tfm mice and from normal mice in which testicular descent was surgically prevented before puberty. As in whole testes, androgen production in response to human chorionic gonadotrophin was severely reduced in Leydig cells from testes of Tfm mice compared with normal or cryptorchid groups. In contrast, progesterone production by Leydig cells from testes of Tfm mice was markedly increased in comparison with other groups. Total steroid production (progesterone plus androstenedione plus testosterone), however, was only 24% of normal in Leydig cells from Tfm mice. The pattern of steroid production by Leydig cells from cryptorchid testes was similar to control, although total steroid production was reduced to about 50% (this was significantly higher than the Tfm group, P less than 0.05). The high progesterone/androgen ratio in testes from Tfm mice suggested that 17 alpha-hydroxylase was depleted in these animals. To confirm this, activity of the four major steroidogenic enzymes associated with the smooth endoplasmic reticulum was measured.(ABSTRACT TRUNCATED AT 250 WORDS)


[Varicella zoster complications].
Varicella zoster virus is known to cause varicella in children and to reactivate years later as shingles. Both the primary disease and the reactivation can cause complications, both in the form of serious affection of organs by the virus itself, and through secondary bacterial infections owing to temporary immune deficiency. Relatively frequent complications include secondary bacterial skin infections, pneumonitis, complications affecting the central nervous system, and hepatitis. We describe a few typical cases seen recently in our department, and review important points connected to treatment and prophylaxis.


Role of FAB classification of acute leukemias in era of immunophenotyping.
French-American-British classification for leukemias had been widely accepted due to its objectiveness and good reproducibility. WHO classification of leukemias was formulated in 1997 with a purpose of further enhancing the objectivity. However, the requirement of cytogenetics and immunophenotyping makes it difficult for many countries like India to put WHO classification in routine use. This study was carried to know the effectiveness of FAB classification in an era of technical advancement. A retrospective analysis of all acute leukemias over a period of 2 years was done. Out of total of 469 cases of acute leukemias, 193 were diagnosed as Acute Lymphoblastic Leukemia (ALL), 200 as Acute Myeloid Leukemia (AML), and 76 cases diagnosed as Acute Leukemia, cytochemically undifferentiated. Hence, only 16% of all leukemias remained unclassifiable. Subclassification of AML cases revealed a much higher percentage of AML-M3, as compared to western literature. In conclusion, FAB classification, based on morphology and simple cytochemical stains, remains effective enough, although cytogenetics and immunophenotyping can add to diagnostic accuracy in some cases.


Microfluidic Surface Plasmon Resonance Sensors: From Principles to Point-of-Care Applications.
Surface plasmon resonance (SPR) is a label-free, highly-sensitive, and real-time sensing technique. Conventional SPR sensors, which involve a planar thin gold film, have been widely exploited in biosensing; various miniaturized formats have been devised for portability purposes. Another type of SPR sensor which utilizes localized SPR (LSPR), is based on metal nanostructures with surface plasmon modes at the structural interface. The resonance condition is sensitive to the refractive index change of the local medium. The principles of these two types of SPR sensors are reviewed and their integration with microfluidic platforms is described. Further applications of microfluidic SPR sensors to point-of-care (POC) diagnostics are discussed.


Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy.
Eleven dogs diagnosed with refractory idiopathic epilepsy were treated orally with gabapentin for a minimum of three months at an initial dose of 10 mg/kg every eight hours. They were all experiencing episodes of generalised tonic-clonic seizures and had been treated chronically with a combination of phenobarbital and potassium bromide at doses sufficient to reach acceptable therapeutic serum levels without causing significant side effects. In each dog, the number of seizures per week, the average duration of the seizures and the number of days on which seizures occurred were compared for the three months before and after they were treated with gabapentin. A minimum 50 per cent reduction in the number of seizures per week was interpreted as a positive response to gabapentin, and six of the dogs showed a positive response. After the addition of gabapentin, both the number of seizures per week (P= 0.005) and the number of days with any seizures in a one-week period (P=0.03) were significantly reduced. Mild side effects of ataxia and sedation were observed in five of the dogs, but they were not severe enough to warrant the treatment being discontinued during the trial.


Molecular mechanics studies on dipeptide models of diphenylalanine and its derivatives.
As a part of our studies on the structure and conformations of peptidomimetics, we present conformational energy calculations on model peptides with (a) diphenyl alanine and its tricyclic derivatives and (b) triphenyl alanine residues using molecular mechanics and conformational analysis methods. The energies are calculated as a function of the backbone torsions (phi and psi), and the results are presented in terms of isoenergy contours in the phi-psi space. The low-energy models adopt conformations characteristic of a variety of regular structures such as the alpha-helix, gamma-turn and polyproline-II-type three- and four-fold helices. The conformational preferences in the model peptides with diphenyl alanine and its tricyclic derivatives are sensitive to the side-chain torsion, with some similarities to the corresponding preferences of L-Ala dipeptide. The energy profile of the model peptide with triphenyl alanine is similar to that of the model peptide with Tle (tert-leucine) residue. The results of our studies have implications in the design of conformationally constrained peptidomimetics with structures in the beta- and alpha-helical regions.


Gene Expression Profiling of Grass Carp (Ctenopharyngodon idellus) and Crisp Grass Carp.
Grass carp (Ctenopharyngodon idellus) is one of the most important freshwater fish that is native to China, and crisp grass carp is a kind of high value-added fishes which have higher muscle firmness. To investigate biological functions and possible signal transduction pathways that address muscle firmness increase of crisp grass carp, microarray analysis of 14,900 transcripts was performed. Compared with grass carp, 127 genes were upregulated and 114 genes were downregulated in crisp grass carp. Gene ontology (GO) analysis revealed 30 GOs of differentially expressed genes in crisp grass carp. And strong correlation with muscle firmness increase of crisp grass carp was found for these genes from differentiation of muscle fibers and deposition of ECM, and also glycolysis/gluconeogenesis pathway and calcium metabolism may contribute to muscle firmness increase. In addition, a number of genes with unknown functions may be related to muscle firmness, and these genes are still further explored. Overall, these results had been demonstrated to play important roles in clarifying the molecular mechanism of muscle firmness increase in crisp grass carp.


A method of calculating the bearing capacity of sand pile composite foundations in a mucky soil layer considering consolidation.
In engineering practice, the measured bearing capacity of a sand pile composite foundation in a mucky soil layer is much larger than the design value. Based on the sand pile construction and the load application process, a method of calculating the bearing capacity of the foundation based on the effective stress was proposed. Cavity diameter expansion in sand pile construction was simplified into a planar problem, and the cavity expansion theory was used to establish the expression of the rate of displacement and the horizontal stress increase. Based on the e-p curve and the calculation of the degree of consolidation, the relationships between the horizontal and vertical effective stress and the void ratio were obtained. According to the close relationship between the bearing capacity of the foundation in a mucky soil layer and the water content, an expression describing the relationships between the bearing capacity of the foundation, effective stress, void ratio, and water content was established. For the temporary engineering foundation treatment project, which needs a high bearing capacity but allows large foundation deformation, the design of sand pile composite foundations uses these relationships to take the consolidation effect of mucky soil into consideration, thereby reducing the replacement rate and lowering the construction cost.


Nontargeted Detection Methods for Food Safety and Integrity.
Nontargeted workflows for chemical hazard analyses are highly desirable in the food safety and integrity fields to ensure human health. Two different analytical strategies, nontargeted metabolomics and chemical database filtering, can be used to screen unknown contaminants in food matrices. Sufficient mass and chromatographic resolutions are necessary for the detection of compounds and subsequent componentization and interpretation of candidate ions. Analytical chemistry-based technologies, including gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and capillary electrophoresis-mass spectrometry (CE-MS), combined with chemometrics analysis are being used to generate molecular formulas of compounds of interest. The construction of a chemical database plays a crucial role in nontargeted detection. This review provides an overview of the current sample preparation, analytical chemistry-based techniques, and data analysis as well as the limitations and challenges of nontargeted detection methods for analyzing complex food matrices. Improvements in sample preparation and analytical platforms may enhance the relevance of food authenticity, quality, and safety.


Influence of a reduced G-suit pressure schedule on G-duration tolerance using enhanced G-protection ensembles.
Reducing pressure to enhanced G-protection ensembles may diminish potential undesirable physiologic effects, as well as improve wear comfort and garment durability. G-duration tolerance will not be affected by reducing pressure to the Swedish tactical flight combat suit (TFCS). A second objective tested the similarity in G-duration tolerance between the TFCS and Combined Advanced Technology Enhanced Design G-Ensemble (COMBAT EDGE) combined with a prototype enhanced coverage G-suit. There were 12 Swedish pilots (mean = 30 yr) who experienced gradual onset (+0.1 G.s-1) runs (GOR) to +9 Gz, rapid (+6 G.s-1) onset runs (ROR) and simulated aerial combat maneuvers (SACM) with +5 to +9 Gz cycles. The GOR and ROR profiles had a sustained times of 60 s after reaching +9 Gz. GOR duration tolerance was statistically decreased (p < 0.01) by the lower pressure (1.1 psig.G-1) when compared to standard pressure (1.5 psig.G-1). No statistical difference between TFCS and COMBAT EDGE was observed during the GOR trials. For all conditions, during the RORs, 90% of the subjects completed at least 30 s at +9 Gz. Many technical or medical difficulties during SACM trials limited statistical treatment of these data. However, no obvious among-condition differences were observed. Noteworthy among SACM trials were those of 3 subjects enduring more than 9 min before stopping; one completing 12.5 min (35 cycles). Neither heart rate, blood pressure, nor perceived exertion data revealed a condition-effect difference. Moderately reduced pressure to the extended coverage anti-G suit, combined with positive pressure breathing, may yield decreased G-tolerance results during laboratory evaluation; however, observed differences are sufficiently small they are likely operationally insignificant.


Betulinic acid and possible influence on the clearance of Human Papilloma Virus: cytological and virological follow-up.
Persistent infection with high-risk Human Papilloma Virus (HPV) types is considered necessary for the development of cervical cancer. No such efficient antiviral agent exists at the present time. The aim of this study was to assess whether the use of topical products, vaginal ovules, containing betulinic acid and betulin may influence viral replication in vivo by promoting its negativity. We enrolled 62 patients at the colposcopy ambulatory with negative colposcopy or with congenital ectopic or normal transformation zone, but with HPV-test positive for high risk. We divided the patients into two groups: group A had no kind of treatment, group B has undergone a treatment with vaginal ovules containing betulinic acid and betulin. All patients have taken a new HPV-test six months after the first control. After six months, we compared the percentage of negative HPV-test. We observed a percentage of negativity of 93% in group B versus 68% in group A. The data was statistically significant at χ2 test (P<0,05). We believe that the results should be investigated further to confirm if there is a correlation between these substances and the increase in the rate of viral negativity.


Stereoselective formation of a functionalized dipeptide isostere by zinc carbenoid-mediated chain extension.
The application of a zinc carbenoid-mediated chain-extension reaction to a functionalized peptide isostere is reported. The cleavage site of human CVM protease was utilized as a target for testing the synthetic methodology. The utility of this chain-extension reaction is demonstrated in the preparation of an amino acid-derived alpha-unsubstituted gamma-keto ester, which is incorporated into a framework that mimics a tetrapeptide. The identification of a suitable protecting group strategy facilitated the application of a tandem reaction for the incorporation of an alpha-side chain, and the use of an oxazolidinone auxiliary provided excellent diastereocontrol in a tandem chain-extension-aldol reaction. Stereoselectivity of the tandem chain-extension-aldol reaction was determined through application of a CAN-mediated oxidative cleavage reaction.


The convergent procedure: a hybrid approach for long lasting persistent atrial fibrillation ablation.
Atrial fibrillation (AF) is associated with increased risk of stroke, heart failure and all-cause mortality. The Cox-Maze procedure is the most effective approach to ablate persistent AF but presents a significant morbidity and mortality. Additionally, the classical endocardial ablation approach has limited efficacy to treat long lasting persistent AF. We described a new, minimally invasive hybrid approach, combining an endocardial and epicardial ablation named convergent procedure to treat long lasting persistent AF patients. We studied 55 consecutive patients with long lasting persistent AF who underwent the convergent procedure in 2 French centers between 2010 and 2015. All patients had at least one previous failed endocardial ablation and were highly symptomatic. Patients with a history of thoracic surgery were excluded. A 24 hour-Holter ECG was performed systematically at 3, 6 and 12 months after the convergent procedure. All patients reached 1-year follow-up. No death, stroke, phrenic nerve palsy or tamponade occurred immediately after the procedure. Post-surgery average length of stay was 8±4 days. Later, 3 patients (5%) developed diaphragmatic hernia resulting in a modified surgery technique. At 12 months, 76% of patients were in sinus rhythm after an average of 1.43 ablation procedure. Finally, 91% of patients were maintained on antiarrhythmic drugs. Thoracoscopic hybrid epicardial-endocardial ablation technique proved to be effective and safe to treat long lasting persistent AF patients with previous failed endocardial AF ablation.


Labour force participation and employment among a sample of Australian patients with a spinal cord injury.
This study examined the employment achievements of 219 spinal cord injured people and attempted to identify predictors which, individually and in combination, (a) discriminated between those who were in the labour force or not, and (b) correlated with the amount of time in employment post injury. Results indicated that at the time of the survey 26% were in full-time work, 11% were in part-time work, 4% were unemployed and 59% were not actively seeking work. Multivariate analyses identified three variables (impairment type, study since injury, level of pre-injury secondary schooling) which were related to both labour force participation and the amount of work undertaken post-injury. These results are discussed with reference to post-injury services that could be offered to spinal cord injury people who wish to return to work or gain employment.


Pregnancy outcome after cerclage for cervical incompetence at the University of Port Harcourt Teaching Hospital, Port Harcourt.
Cervical incompetence is often associated with mid trimester pregnancy losses and preterm labour. cervical cerclage to prevent miscarriage and preterm labour is practiced world wide. The objective of this study was to document the feto-maternal outcome following cervical cerclage for cervical incompetence. The study reviewed all case files of pregnant women who had cervical cerclage for cervical incompetence between January 1, 2004 to December 31, 2008, at the University of Port Harcourt Teaching Hospital. The study found an incidence of 0.17% of cervical incompetence among the antenatal population. Following cervical cerclage, miscarriage rate was 9.4%. Preterm delivery occurred in 21.8% while term pregnancy occurred in 68.8% of the women. There is improvement in pregnancy outcome after cervical cerclage for cervical incompetence hence we recommend the insertion for true cases of cervical incompetence.


Biological activity of C-terminal partial sequences of substance P.
Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) and the C-terminal partial sequences down to the tripeptide were synthesized by a solid-phase method. These peptides were assayed for vasodilator, spasmogenic, and venoconstrictor properties using three preparations, viz. the hind limb blood flow of the dog, isolated guinea pig ileum, and the isolated rabbit ear vein. The tripeptide and tetrapeptide possessed weak vasodilator properties only but no activity was detected on the other less sensitive preparations. The pentapeptide produced appreciable spasmogenic and vasoactive effects. Sequences of six or more C-terminal amino acids were able to elicity activity at comparable doses to that of the parent endecapeptide; however, the activity did not increase regularly with the chain length. In each assay preparation the octapeptide was the most potent peptide. It was twice as potent as substance P on a molar basis in the guinea pig ileum but the enhancement of activity beyond that of substance P was less pronounced in the vascular preparations.


Role of Magnetic Resonance Imaging in Differentiating Spondylitis from Vertebral Metastasis.
Observational analytic design with a cross-sectional approach. To analyze the suitability of magnetic resonance imaging (MRI) in distinguishing radiology images with a corresponding delineation of spondylitis and vertebral metastasis confirmed by histology results. MRI is an accurate modality for assessing vertebrae and their disorders. Infections and metastasis are most commonly found in the vertebrae. It is difficult to differentiate between these two disorders both clinically and radiographically, particularly in atypical cases. McNemar statistical test was used to analyze the data. Samples were chosen using the consecutive method. There were 35 samples (14 males and 21 females), consisting of 22 samples of spondylitis and 13 samples of metastasis confirmed on histology examination. Nineteen (86%) out of the 22 samples of histological spondylitis were diagnosed as having spondylitis on MRI, whereas all 13 samples of metastasis were 100% accurately diagnosed on MRI. There was no statistically significant difference between diagnostic radiology using MRI and histological diagnosis with a p=0.250 (p>0.05). In this respect, MRI was more precise in diagnosing metastasis. Typical MRI description of spondylitis was the involvement of anterior vertebrae and components of intervertebral discs, stiffening of discs, paravertebral abscess, and involvement of the vertebral segment sequence. Typical MRI delineation of metastasis was involvement of the anterior posterior vertebral component, paravertebral mass, and skip lesions.


Copper-Catalyzed Intermolecular Reductive Radical Difluoroalkylation-Thiolation of Aryl Alkenes.
A novel radical-involved alkene difunctionalization catalyzed by the copper/B2pin2 system has been developed, leading to the difluoroalkylation-thiolation of aryl alkenes. The use of B2pin2 as an organic reductant enables the simultaneous installation of a C(sp3)-C(F2R) bond and a C(sp3)-S(R) bond across the C═C bond of aryl alkenes by utilizing two electrophilic reactants. The reaction exhibits broad substrate scope, excellent diastereoselectivity, and moderate to good yields. Moreover, the reaction can be conducted on a gram scale with good yield achieved.


An in situ grown ultrathin and robust protein nanocoating for mitigating thromboembolic issues associated with cardiovascular medical devices.
Thromboembolism, arising from the utilization of cardiovascular medical devices, remains a prevalent issue entailing substantial morbidity and mortality. Despite the proposal of various surface modification strategies, each approach possesses inherent limitations and drawbacks. Herein, we propose a novel approach for the in situ growth of nanocoatings on various material surfaces through the cooperative assembly of silk fibroin (SF) and lysozyme. The intrinsic in situ growth characteristic enables the nanocoatings to achieve stable and uniform adherence to diverse substrate surfaces, including the inner surface of intravascular catheters, to redefine the surface properties of the material. The features of the hydrophilic and negatively charged nanocoating contribute to its antithrombotic properties, as evidenced by the reduced likelihood of platelet adhesion upon modification of the ultrathin and mechanically robust coating. In vitro assessment confirms a significant reduction in blood clot formation along with the promotion of anticoagulation. Such a SF/Ly nanocoating holds substantial promise as a surface modification strategy to enhance the hemocompatibility of medical devices and other materials that come into contact with blood, particularly in situations where medical-grade materials are temporarily unavailable, thus providing a feasible alternative.


Transcranial Doppler monitoring in angioplasty and stenting of the carotid bifurcation.
To assess the impact of cerebral embolism and hemodynamic changes during the successive stages of carotid angioplasty and stenting (CAS) using transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA). In 297 patients (206 men; mean age 69.9+/-8.0 years), the association of various TCD emboli and velocity variables with procedure-related death and cerebral events (amaurosis fugax, transient ischemic attacks, and stroke) was evaluated. Baseline patient characteristics (age, sex, preoperative cerebral symptoms, and prior carotid endarterectomy) and their associations with procedure-related cerebral events were also assessed. A distinction was made between adverse events that occurred during CAS and those that happened within 7 days. Of the 36 procedure-related retinal and cerebral events, 28 (78%) were encountered intraprocedurally; an additional 6 (2%) events occurred within 7 days after the procedure. Two (0.7%) patients died. At 1 week, the combined minor and major stroke and death rate was 3.7%. Adverse outcome was associated with >4 showers of microemboli at postdilation (odds ratio [OR] 3.2, 95% CI 1.3 to 7.8, p=0.03), particulate macroemboli (OR 9.1, 95% CI 5.1 to 16.1, p<0.001), massive air embolism from ruptured balloons (OR 11.3, 95% CI 7.6 to 16.6, p<0.001), and angioplasty-induced asystole with significant hypotension plus MCA blood flow reduction (OR 3.3, 95% CI 1.4 to 8.3, p=0.03). Of the patient characteristics, male gender (OR 10.5, 95% CI 1.4 to 75.8, p=0.02) and preoperative cerebral ischemia (OR 3.3, 95% CI 1.6 to 6.6, p=0.003) were also related to outcome. In CAS, TCD monitoring provides insight into the pathogenesis of procedure-related cerebral events. Microemboli during poststent dilation, particulate macroembolism, massive air embolism, and angioplasty-induced asystole are associated with adverse outcome, as are male gender and prior cerebral ischemia.


Angiotensin II system in the nucleus tractus solitarii contributes to autonomic dysreflexia in rats with spinal cord injury.
Autonomic dysreflexia (AD) is a potentially life-threating complication after spinal cord injury (SCI), characterized by episodic hypertension induced by colon or bladder distension. The objective of this study was to determine the role of impaired baroreflex regulation by the nucleus tractus solitarii(NTS) in the occurrence of AD in a rat model. T4 spinal cord transection animal model was used in this study, which included 40 Male rats Colorectal distension (CD) was performed to assess AD and compare the changes of BP, HR, and BRS, six weeks after operation. After that, SCI rats with successfully induced AD were selected. Losartan was microinjected into NTS in SCI rats, then 10, 30, 60 minutes later, CD was performed to calculate the changes of BP, HR, and BRS in order to explicit whether Ang II system was involved in the AD occurrence. Ang II was then Intra-cerebroventricular infused in sham operation rats with CD to mimic the activation of Ang II system in AD. Finally, the level of Ang II in NTS and colocalization of AT1R and NMDA receptor within the NTS neurons were also detected in SCI rats. Compared with sham operation, SCI significantly aggravated the elevation of blood pressure (BP) and impaired baroreflex sensitivity (BRS) induced by colorectal distension; both of which were significantly improved by microinjection of the angiotensin receptor type I (AT1R) antagonist losartan into the NTS. Level of angiotensin II (Ang II) in the NTS was significantly increased in the SCI rats than sham. Intracerebroventricular infusion of Ang II also mimicked changes in BP and BRS induced by colorectal distension. Blockade of baroreflex by sinoaortic denervation prevented beneficial effect of losartan on AD. We concluded that the activation of Ang II system in NTS may impair blood pressure baroreflex, and contribute to AD after SCI.


The Effects of an Oral Taurine Dose and Supplementation Period on Endurance Exercise Performance in Humans: A Meta-Analysis.
Taurine is central to many physiological processes, some of which are augmented by exogenous supply and have the potential to facilitate endurance performance; however, its independent effects on performance have not been systematically analysed. To evaluate the effects of isolated oral taurine ingestion on endurance performance and to assess the contribution of (1) the dose and (2) the supplementation period to the ergogenic effect. A search was performed using various databases in September 2017. The studies were screened using search criteria for eligibility. Ten peer-reviewed articles were identified for inclusion. A sub-analysis of time-to-exhaustion (TTE) trials (n = 7) was also performed. The effects of (1) dose and (2) the acute (single dose) or chronic (> 1 day) supplementation periods were assessed using meta-regression. The doses of taurine ranged from 1 to 6 g/day and were provided in single doses and for up to 2 weeks among a range of subjects. Taurine ingestion improved overall endurance performance (Hedges' g = 0.40, 95% CI 0.12-0.67, P = 0.004), which was similar in TTE trials (Hedges' g = 0.43, 95% CI 0.12-0.75, P = 0.007). There were no differences between acute or chronic supplementation for the full sample (P = 0.897) or the TTE group (P = 0.896). The dose of taurine did not moderate its effect on endurance performance (P > 0.05). Human endurance performance can be improved by orally ingesting a single dose of taurine in varying amounts (1-6 g).


Calcaneus secundarius: an osteo-archaeological note.
Calcaneus secundarius, a minor anatomical variant in the foot, is subclinical and its true prevalence in modern populations is uncertain. The trait is clearly visible in dry bones, and osteo-archeological evidence suggests that it may be a more frequent occurrence than was formerly thought. The etiology of the trait is outlined, and its possible value is assessing "biological distance" in past populations is considered.


Overview of simulation studies on the enzymatic activity and conformational dynamics of the GTPase Ras.
Over the last 40 years, we have learnt a great deal about the Ras onco-proteins. These intracellular molecular switches are essential for the function of a variety of physiological processes, including signal transduction cascades responsible for cell growth and proliferation. Molecular simulations and free energy calculations have played an essential role in elucidating the conformational dynamics and energetics underlying the GTP hydrolysis reaction catalysed by Ras. Here we present an overview of the main lessons from molecular simulations on the GTPase reaction and conformational dynamics of this important anti-cancer drug target. In the first part, we summarise insights from quantum mechanical and combined quantum mechanical/molecular mechanical simulations as well as other free energy methods and highlight consensus viewpoints as well as remaining controversies. The second part provides a very brief overview of new insights emerging from large-scale molecular dynamics simulations. We conclude with a perspective regarding future studies of Ras where computational approaches will likely play an active role.


[Fraud in medicine with the child as victim. Munchausen syndrome by proxy. A review of the literature].
In a review of the literature on the subject 'Münchhausen syndrome by proxy' the authors try to give an impression of the history of diagnosis and treatment of this special kind of child abuse. Particularly aspects of confrontation are discussed. They consider features of the chief actors in this very dramatic play. The authors point to problems in differential diagnosis in the framework of other subjects like 'non-accidental poisoning', 'doctor-shopping' and 'filicide'. They discuss ethical and legal consequences.


Effectiveness and safety of anti-IL-5/Rα biologics in eosinophilic granulomatosis with polyangiitis: a two-year multicenter observational study.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia. To assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months. We conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed. 49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all p<0.05), but began to decline from month 12, especially with mepolizumab. Marked reduction in blood eosinophils was registered with mepolizumab (p<0.0001), while benralizumab depleted both eosinophils (p<0.0001) and basophils (p<0.0001). In general, 69.6% (76% benralizumab and 61.9% mepolizumab) of OCS-dependent patients lowered their daily dose by 75%, while 28.3% discontinued these drugs. Immunosuppressants were suspended in 88.2% of cases. Adverse events were reported in 8.2% of patients. These real-world data suggest that anti-IL-5/Rα biologics are effective and safe in the long-term as add-on treatments for patients with EGPA.


Radiation therapy in the management of patients with mesothelioma.
The results of radiation therapy in the management of 27 patients with malignant mesothelioma were reviewed. Eight patients were treated with a curative intent combining attempted surgical excision of tumor (thoracic in 6 and peritoneal in 2), aggressive radiation therapy, and combination chemotherapy using an adriamycin-containing regimen. One patient achieved a 2-year disease-free interval followed by recurrence of tumor above the thoracic irradiation field. This patient was retreated with localized irradiation and is disease-free after 5 years of initial diagnosis. One patient has persistent abdominal disease at 18 months; the other 6 patients suffered local recurrence within 8-13 months of initiation of treatment. Radiation therapy was used in 19 other patients who received 29 courses for palliation of dyspnea, superior vena cava syndrome, dysphagia, or neurological symptoms of brain metastasis. A palliation index was used to determine the effectiveness of irradiation and revealed that relief of symptoms was complete or substantial in 5 treatment courses, moderately effective in 6 courses and inadequate in 18 treatment courses. Adequate palliation strongly correlated with a dose at or above 4,000 rad in 4 weeks. The management of patients with mesothelioma requires new and innovative approaches to increase the effectiveness of radiation therapy and minimize the significant potential combined toxicity of pulmonary irradiation and adriamycin.


Characteristics of Team Physicians in the National Football League: The Road to Success and a Call for Diversity.
The role of team physician (TP) in professional sports is a highly coveted position within sports medicine. There is currently limited research on the demographic characteristics of TPs within the National Football League (NFL). To identify demographic characteristics and educational backgrounds of NFL head TPs (HTPs) and assistant TPs (ATPs). Cross-sectional study. A list of TPs was identified through the National Football League Physicians Society (NFLPS). Variables investigated include age, gender, race, medical specialty, location and year of residency and fellowship training, leadership among medical societies and editorial boards, academic rank, and personal Scopus Hirsch index (h-index). Linear regression was performed to determine correlation, and t tests were used to assess differences in the h-index. Of the 170 TPs, 21.2% were HTPs and 78.8% were ATPs. TPs were 97.6% male, 91.2% were non-Hispanic White, and 60% had attained an academic rank. The mean ages of the HTPs and ATPs were a 56.2 ± 9.6 and 52.6 ± 9.6 years, respectively (P = .047). Among orthopaedic surgeons, the most common subspecialties were sports medicine (70.5%), foot and ankle (7.6%), and spine (5.7%). Of the TPs, 48.2% and 32.9% worked for a team in the same state in which they graduated residency and fellowship, respectively. HTPs and ATPs had been in the NFLPS for a mean of 16.9 ± 10.8 and 8.8 ± 8.3 years, respectively (P < .001). Further, TPs holding an academic rank had a mean h-index of 14.0 ± 19.3, while those without an academic rank had a mean h-index of 6.2 ± 8.8 (P < .01). HTPs and ATPs had mean h-indices of 15.7 ± 15.9 and 9.6 ± 16.3 (P = .0503), respectively. TPs in the NFL are typically White men in their mid-50s who have trained at specific high-ranking institutions and obtained a fellowship in sports medicine. HTPs were likely to be older with longer tenures within the NFLPS and with more impactful research than their ATP counterparts.


The morphology of cyamella and its prevalence in Turkish society.
The aim of this study is to determine the prevalence and morphometry of cyamella, one of the sesamoid bones around the knee joint. In this retrospective study, a total of 9,500 plain/digital radiographs of 6,500 patients over the age of 18 who applied to Elazig Fethi Sekin City Hospital between January 2021 and January 2022 were examined. Examinations revealed cyamella in a total of 76 (0.8%) knees in the direct X-ray images of 49 (0.75%) patients. Eighteen (36.74%) of the patients with the presence of cyamella were males, and 31 (63.26%) were females. The mean age of the patients with cyamella was 50.9±12.9. Twenty-seven (55.1%) of the 49 cyamella were bilateral; seven (14.3%) were in the right knee, and 15 (30.6%) were in the left knee. The comparison of cyamella sizes between genders revealed a statistically significant difference in the transverse measurements only (p=0.015) in the right knee, while a statistically significant difference was found in all 3 parameters (p=0.032 for thickness; p=0.04 for transverse; p=0.026 for length) in the left knee. We believe that sufficient knowledge regarding the prevalence and distribution of cyamella in patients presenting with the complaint of knee pain and its differentiation from fabella, another sesamoid bone in the same region, as well as other anatomical structures, will aid an early and accurate diagnosis.


[Surgical treatment of radiation-induced lesions of the hip in adults].
The authors report their experience in the surgical management of lesions of the adult hip following radiotherapy. The diagnosis of a hip problem occurring after pelvic radiotherapy for malignant tumors is made by clinical and radiological examination. The problems include femoral head necrosis, necrosis and/or fracture of the acetabulum, or involvement of the entire hip joint (radiation coxopathy). Fractures of the femoral neck have been described in the literature, but are now very rare following the routine use of external shields as protection during irradiation. Post-irradiation lesions are often bilateral 21%. They appear after a variable latency period of two to twenty years and they progress remorselessly. A diagnosis of simple radio necrosis can only be made after using radio isotope bone scanning, MRI or CT to exclude malignant disease as acetabular metastasis, and radio-induced sarcomas. Hemiarthroplasty is often followed by collapse of the acetabulum and should no longer be used. The treatment generally practised nowadays is a Total Hip Replacement (THR). We report a retrospective study of 71 hips in 56 patients treated, between 1970 and 1982, by the use of conventional cemented components. In 49 hips this was followed by a 52% incidence of acetabular loosening resulting from the poor quality of the irradiated bone which had become necrotic and porotic. Between 1983 and 1990, we modified the technique by regularly using reinforcing the acetabulum with a metallic ring fixed by long screws, (as used in revision surgery for THR). Bone grafts were also used in 9 cases. We had a 12% incidence of loosening in 22 hips with a mean follow-up of 40 months. There were also two post-operative infection which need removal of the prostheses. This emphasizes the risk of infection in this type of surgery and is probably increased by the associated lesions of the soft tissues (lymphoedema, radiodermitis). The authors wish to stress the poor prognosis of radiation lesions of the hip which often occur in patients who have otherwise recovered from their pelvic tumour. These radiation lesions have to be recognised and treated in a specific way. Our experience and the reports in the literature suggest that the generally used conventional THR gives uncertain results, and therefore we propose a THR employing metallic reinforcement of the acetabulum with or without any necessary bone grafts. It is vital to warn the patients that the results may not be as excellent as with THR for other types of hip disorders. When there is severe destruction of the acetabulum the choice between a THR combined with massive bone allograft, and a Girdlestone hip resection must be very carefully discussed with the patient. This latter "salvage" procedure may in any case become necessary if there are local and otherwise unmanageable problems.


Risk factors of lower urinary tract injury with laparoscopic sacrocolpopexy.
Lower urinary tract injuries can occur during pelvic reconstructive surgery, including sacrocolpopexy. The reported injury rates range from 0.4% to 10.6% with laparoscopic sacrocolpopexy, 1.1% to 3.3% with abdominal sacrocolpopexy, and 2.3% to 10% with robotic sacrocolpopexy. Specific literature identifying the risk factors for lower urinary tract injury during pelvic reconstructive surgery is lacking; therefore; we aim to identify the patient characteristics predisposing a patient to lower urinary tract injury during laparoscopic sacrocolpopexy. The primary objective of this study was to identify the patient-specific risk factors for lower urinary tract injury with laparoscopic sacrocolpopexy. This was an age-matched, case-control study including patients who underwent laparoscopic sacrocolpopexy from July 2014 to December 2017 in a high-volume female pelvic medicine and reconstructive surgery practice. The patients were excluded if they underwent laparoscopic uterosacral ligament suspension, had abnormal urinary tract anatomy, or for incorrect, incomplete, or duplicated data. Risk factors such as race, body mass index, pelvic organ prolapse quantification stage, previous abdominal and/or vaginal surgeries, and concurrent procedures (lysis of adhesions, adnexal surgery, midurethral sling placement, and anterior or posterior colporrhaphy) were analyzed. Groups were compared using the Student t-test for independent samples and chi-square tests. Conditional logistic regression was used to estimate the crude and adjusted odds ratios. A total of 930 patients were identified during electronic medical record chart review using the current procedural terminology code 57425 (laparoscopic colpopexy). A total of 167 patients met the exclusion criteria, resulting in a total of 763 patients for primary analysis. The prevalence of lower urinary tract injury was 2.4% (17 bladder injuries and 1 ureteral injury out of 763 laparoscopic sacrocolpopexy procedures). These 18 cases were age-matched to 72 controls. The mean age and body mass index of all patients was 64.8 years (±9.32) and 26.5 kg/m2 (±3.99), respectively. Most of the patients were Caucasian, had previously undergone abdominal and/or vaginal surgery, had pelvic organ prolapse stage 3 or greater, and underwent concurrent surgeries, including adnexal surgery and midurethral sling placement at the time of laparoscopic sacrocolpopexy. A history of previous hysterectomy (odds ratio, 19.94; 95% confidence interval, 2.48-160.38; P=.005) and lysis of adhesions at the time of laparoscopic sacrocolpopexy (odds ratio, 4.94; 95% confidence interval, 1.05-23.19; P=.043) were associated with an increased odds of lower urinary tract injury in unadjusted models. In a multivariable logistic regression model controlling for the previously listed variables, a history of previous hysterectomy remained significantly associated with lower urinary tract injury (adjusted odds ratio, 162.41; 95% confidence interval, 3.21-8227; P=.011). Race, body mass index, pelvic organ prolapse quantification system stage, previous abdominal and/or vaginal surgery, and concurrent procedures were not associated with an increased risk of lower urinary tract injury. Although lower urinary tract injury with laparoscopic sacrocolpopexy only occurred in 2.4% of patients, previous hysterectomy increased this risk substantially. As sacrocolpopexy is the common treatment for prolapse after hysterectomy or recurrent prolapse, this increased risk of lower urinary tract injuries can guide surgical counseling on the basis of patient-specific risk factors and aid in setting appropriate postoperative patient expectations.


Cellular circadian oscillators in the suprachiasmatic nucleus remain coupled in the absence of connexin-36.
In mammals, the master circadian clock resides in the suprachiasmatic nucleus (SCN). The SCN is characterized by robust circadian oscillations of clock gene expression and neuronal firing. The synchronization of circadian oscillations among individual cells in the SCN is attributed to intercellular coupling. Previous studies have shown that gap junctions, specifically those composed of connexin-36 (Cx36) subunits, are required for coupling of electrical firing among SCN neurons at a time scale of milliseconds. However, it remains unknown whether Cx36 gap junctions also contribute to coupling of circadian (∼24h) rhythms of clock gene expression. Here, we investigated circadian expression patterns of the clock gene Period 2 (Per2) in the SCN of Cx36-deficient mice using luminometry and single-cell bioluminescence imaging. Surprisingly, we found that synchronization of circadian PER2 expression rhythms is maintained in SCN explants from Cx36-deficient mice. Since Cx36 expression levels change with age, we also tested circadian running-wheel behavior of juvenile (3-4weeks old) and adult (9-30weeks old) Cx36-deficient mice. We found that impact of connexin-36 expression on circadian behavior changes greatly during postnatal development. However, consistent with the intact synchrony among SCN cells in cultured explants, Cx36-deficient mice had intact locomotor circadian rhythms, although adults displayed a lengthened period in constant darkness. Our data indicate that even though Cx36 may be required for electrical coupling of SCN cells, it does not affect coupling of molecular clock gene rhythms. Thus, electrical coupling of neurons and coupling of circadian clock gene oscillations can be regulated independently in the SCN.


Reversible arterial spasm in an adolescent with primary oxalosis.
A 16-year-old girl with primary oxalosis type I presented with progressive claudication soon after being treated with chronic intermittent hemodialysis. Arterial insufficiency of the lower limbs was confirmed clinically (purple discoloration of the skin and absence of arterial pulses) and with Doppler sonography. The arteriogram showed diffuse and symmetric narrowing with smooth vessel walls. Treatment with sodium nitroprusside had a spectacular effect; nifedipine was less effective. Renal transplantation with the father's kidney resulted in a rapid, complete and sustained reversal of the ischemic features. Magnesium withdrawal is assumed to be a pathogenic factor of the vascular spasm in this patient.


In vivo and ex vivo evaluation of cosmetic properties of seedcakes.
The seedcakes are a potential source of natural bioactive substances: antioxidants, protein, and carbohydrates. Thus, they may scavenge free radicals and have an effect on the stratum corneum hydration and epidermal barrier function. The aim of the study was to evaluate the in vivo and ex vivo properties of emulsions with the seedcake extracts using the pH meter, corneometer, tewameter, methyl nicotinate model of micro-inflammation in human skin, and tape stripping of the stratum corneum. The in vivo and ex vivo studies showed that the emulsions with Oenothera biennis, Borago officinalis, and Nigella sativa seedcake extracts have anti-inflammatory and antioxidant activity. The 6-week topical application of the emulsions with the B. officinalis and N. sativa seedcakes significantly reduced skin irritation and influenced the improvement of the skin hydration and epidermal barrier function compared with placebo. The seedcakes due to their antioxidant and anti-inflammatory activities have potential application in anti-aging, moisturizing, mitigating, and protective cosmetics.


Nutritional modulation of metabolic inflammation.
Metabolic inflammation is a very topical area of research, wherein aberrations in metabolic and inflammatory pathways probably contribute to atherosclerosis, insulin resistance (IR) and type 2 diabetes. Metabolic insults arising from obesity promote inflammation, which in turn impedes insulin signalling and reverse cholesterol transport (RCT). Key cells in the process are metabolically activated macrophages, which up-regulate both pro- and anti-inflammatory pathways in response to lipid spillover from adipocytes. Peroxisome proliferator-activated receptors and AMP-activated protein kinase (AMPK) are regulators of cellular homeostasis that influence both inflammatory and metabolic pathways. Dietary fats, such as saturated fatty acids (SFAs), can differentially modulate metabolic inflammation. Palmitic acid, in particular, is a well-characterized nutrient that promotes metabolic inflammation via the NLRP3 (the nod-like receptor containing a pyrin domain) inflammasome, which is partly attributable to AMPK inhibition. Conversely, some unsaturated fatty acids are less potent agonists of metabolic inflammation. For example, monounsaturated fatty acid does not reduce AMPK as potently as SFA and n-3 polyunsaturated fatty acids actively resolve inflammation via resolvins and protectins. Nevertheless, the full extent to which nutritional state modulates metabolic inflammation requires greater clarification.


Engineered Nano-Bio Interfaces for Stem Cell Therapy.
Engineered nanomaterials (ENMs) with different topographies provide effective nano-bio interfaces for controlling the differentiation of stem cells. The interaction of stem cells with nanoscale topographies and chemical cues in their microenvironment at the nano-bio interface can guide their fate. The use of nanotopographical cues, in particular nanorods, nanopillars, nanogrooves, nanofibers, and nanopits, as well as biochemical forces mediated factors, including growth factors, cytokines, and extracellular matrix proteins, can significantly impact stem cell differentiation. These factors were seen as very effective in determining the proliferation and spreading of stem cells. The specific outgrowth of stem cells can be decided with size variation of topographic nanomaterial along with variation in matrix stiffness and surface structure like a special arrangement. The precision chemistry enabled controlled design, synthesis, and chemical composition of ENMs can regulate stem cell behaviors. The parameters of size such as aspect ratio, diameter, and pore size of nanotopographic structures are the main factors for specific termination of stem cells. Protein corona nanoparticles (NPs) have shown a powerful facet in stem cell therapy, where combining specific proteins could facilitate a certain stem cell differentiation and cellular proliferation. Nano-bio reactions implicate the interaction between biological entities and nanoparticles, which can be used to tailor the stem cells' culmination. The ion release can also be a parameter to enhance cellular proliferation and to commit the early differentiation of stem cells. Further research is needed to fully understand the mechanisms underlying the interactions between engineered nano-bio interfaces and stem cells and to develop optimized regenerative medicine and tissue engineering designs.


Cesarean delivery on maternal request versus planned vaginal delivery: impact on development of pelvic organ prolapse.
Pelvic floor disorders (PFDs) (ie, pelvic organ prolapse, urinary and fecal incontinence) are prevalent and impact quality of life as well as our health care system. It has been estimated that the demand for health care related to PFDs will increase at twice the rate of the population itself. This speaks to the fact that PFDs are an important women's and public health issue, warranting studies aimed at their prevention.


[Psychiatric disorders in non demented elderly people].
Psychogeriatrics is a rapidly growing field. In France, the focus is currently on targeted education and specific management. Psychiatric disorders may be atypical in the elderly, and may also be difficult to distinguish from the effects of aging or somatic disorders. The principal disorders observed in old age are depression, late delusion, anxiety disorder, hysteria, delirium and mania. Depression has specific features, depressive equivalents, particular risk factors, and a categorical and dimensional therapeutic approach. Diagnosis and screening must be improved Late delusion is organized around a notion of injury, and is an active attempt to deal with isolation, depression and anxiety. The term "very late-onset schizophrenia-like psychosis" has been proposed. Anxiety also has specific features in the elderly and is intimately related to depression. If left untreated, the consequences can be severe. Hysteria is pathoplastic with time, age and educational status. Pseudocognitive conversions are starting to be seen in old age. Delirium is very frequent in the elderly; it is often multifactorial, but psychosocial factors must not be underestimated. Mania can also be provoked by somatic disease, and mixed syndromes are far from rare. Dementia can be approached from its psychopathological dimension, particularly in terms of psychosocial risk factors and protective factors relating to the individual's biography and personality. Thus, psychogeriatrics is an integrated medical discipline in which psychiatric disorders are approached through specific clinical management, oriented research and structured training.


Mapping of conformational mAb epitopes to the C domain of human angiotensin I-converting enzyme.
Angiotensin I-converting enzyme (ACE, CD143) has two homologous domains, each having a functional active site. Fine epitope mapping of 8 mAbs to the C-terminal domain of human ACE was carried out using plate precipitation assays, mAbs' cross-reactivity with ACE from different species, site-directed mutagenesis, and antigen- and cell-based ELISAs. Almost all epitopes contained potential glycosylation sites. Therefore, these mAbs could be used to distinguish different glycoforms of ACE expressed in different tissues or cell lines. mAbs 1B8 and 3F10 were especially sensitive to the composition of the N-glycan attached to Asn 731; mAbs 2H9 and 3F11 detected the glycosylation status of the glycan attached to Asn 685 and perhaps Asn1162; and mAb 1E10 and 4E3 recognized the glycan on Asn 666. The epitope of mAb 1E10 is located at the N-terminal end of the C domain, close to the unique 36 amino acid residues of testicular ACE (tACE). Moreover, it binds preferentially to tACE on the surface of human spermatozoa and thus may find application as an immunocontraceptive drug. mAb 4E3 was the best mAb for quantification of ACE-expressing somatic cells by flow cytometry. In contrast to the other mAbs, binding of mAb 2B11 was not markedly influenced by ACE glycosylation or by the cell culture conditions or cell types, making this mAb a suitable reference antibody. Epitope mapping of these C-domain mAbs, particularly those that compete with N-domain mAbs, enabled us to propose a model of the two-domain somatic ACE that might explain the interdomain cooperativity. Our findings demonstrated that mAbs directed to conformational epitopes on the C-terminal domain of human ACE are very useful for the detection of testicular and somatic ACE, quantification using flow cytometry and ELISA assays, and for the study of different aspects of ACE biology.


Femoral hernia in the female.
A study of 384 consecutive femoral herniorrhaphies performed upon female patients admitted to Shouldice Hospital, Toronto, during a 19-year period was carried out. Its main purpose was to describe the techniques used and to evaluate the results obtained. A careful 10-year follow-up plan for all cases existed.Two hundred and ninety-three operations were performed for the repair of simple femoral hernia; 91 were performed for the repair of femoral hernia which had developed following an initial ipsilateral inguinal or femoral repair performed previously, either in this hospital or elsewhere.The basic repair was subinguinal. Four modifications are described, one entirely subinguinal and three combined with exploration of the inguinal canal.The recurrence rate for simple femoral hernia in the female was 1.3% and for "recurrent" femoral hernia in the female, 5.5%.


Muscle energy technique in patients with acute low back pain: a pilot clinical trial.
A prospective, pilot clinical trial. Examining the outcomes of Muscle Energy Technique (MET) in patients with acute low back pain. MET is commonly used to treat patients with acute low back pain. No randomized controlled trials examining the outcomes of this treatment in symptomatic populations has been reported in the literature. Ten men and 9 women diagnosed with acute low back pain were randomly assigned with stratification to 1 of 2 treatment groups. Patients were matched according to age, gender, and initial Oswestry score. The control group received supervised neuromuscular re-education and resistance training while the experimental group received the same exercises coupled with MET. Both groups received the selected treatment 8 times over a 4-week period (2 times per week). Patients completed an Oswestry Disability Index on their first and eighth visits and change scores were calculated. A 2-tailed t test (P < .05) demonstrated a statistically significant difference with the experimental group showing greater improvement in the Oswestry Disability Index score than the control group. MET combined with supervised motor control and resistance exercises may be superior to neuromuscular re-education and resistance training for decreasing disability and improving function in patients with acute low back pain.


The Impact of Multimorbidity on Resting Metabolic Rate in Community-Dwelling Women over a Ten-Year Period: A Cross-Sectional and Longitudinal Study.
Ageing has been associated with increasing multimorbidity. This study investigated whether the number of diseases is a predictor of resting metabolic rate (RMR) and its long-term changes in community-dwelling elderly women. Cross-sectional and longitudinal data, obtained over ten years with repeated follow-ups, from 180 women aged 60 - 86 years and with a BMI of 18 - 43 kg/m2 at baseline were analyzed. RMR was measured using indirect calorimetry and body composition by bioelectrical impedance analysis. Diagnosed diseases were assessed by a questionnaire comprising 23 disease categories. Subjects with 0 - 2 diseases were classified as relatively healthy and with > 2 diseases as multimorbid. At baseline, relatively healthy (N = 75) and multimorbid (N = 105) women did not differ in RMR. During the ten-year follow-up, the median (range) number of diseases increased from 2 (0 - 2) to 4 (0 - 8) in relatively healthy and from 5 (3 - 11) to 7 (3 - 15) in multimorbid women. In the longitudinal analyses, only women who were multimorbid at baseline showed a significant increase in RMR of 31 kJ/d per additional disease (P = 0.015), adjusted for fat-free mass, fat mass, waist circumference and age. Increasing multimorbidity in community-dwelling women is associated with an increase in RMR independently of body composition and age.


Straddle injury with anal sphincter and rectal rupture in a young girl Case report.
As a result of increasing sport or car accident, straddle injuries in pediatric age are becoming increasingly frequent. Mild lesions of the external genitalia and urinary apparatus, are mainly observed in blunt trauma, whereas more severe lesions are reported in penetrating injuries; however, ano-rectal involvement alone, has been reported very rarely and especially in penetrating trauma. We describe herein a case of straddle trauma occurring in a 14yr old girl involved in a car accident. The girl reported anal sphincter rupture and rectal wall tear with a blunt mechanism. No other involvement of genitourinary apparatus was observed. The diagnostic and surgical approach of this rare consequence of a straddle, blunt injury are described and commented. Anal sphincter rupture, Emergency laparoscopy, Perineal trauma, Rectal lesion, Straddle injury.


[Determination of serum Fe in prostatic pathology].
We have determined serum Fe concentrations in 75 patients whose post-surgical anatomo-pathological diagnostic was: 25 cases with prostate benign hyperplasia, 25 cases where besides hyperplasia there was also an associated chronic prostatitis and 25 cases of moderately differentiated prostatic adenocarcinoma stage D according to the Jewett classification. No patient had received prior medication nor had associated metabolic pathology. Serum Fe concentration was significantly decreased in the cases with prostatic adenocarcinoma. The methodology used for these determinations is presented, discussing the possible pathogenic hypothesis explaining this finding together with the clinical consequences.


Study on the Filtration Performance of the Baghouse Filters for Ultra-Low Emission as a Function of Filter Pore Size and Fiber Diameter.
The main objective of this study was to determine the effect of filter pore size and fiber diameter on the performance of the baghouse filters for ultra-low emission. In this study, three kinds of conventional polyester filter (depth filtration media) and two kinds of polytetrafluoroethylene membrane-coated polyester filter (surface filtration media), having various filter pore sizes and fiber diameters, were tested to determine the performance of static and dynamic filtration. In order to determine the static filtration performance, the filtration resistance and the filtration efficiency of the clean filter media were measured by the arrestance method. The dynamic filtration performance experiments were conducted to determine the dynamic resistances, dust depositions, and dynamic filtration efficiencies of the dust-containing filter media under the condition of dust airflow filtration through a pulse-cleaning cycle. In the dynamic filtration performance experiments, the size of 50% test dust was less than 2.5 μm, and the mass mean aerodynamic diameter of the dust was 1.5 μm. The filtration velocity was 2 m∙min-1, and the dust concentration was 18.4 g∙m-3. The static filtration performance experiments showed that the filter pore size greatly affected the filtration resistance and the filtration efficiency of the fabric structure of the surface filtration media. In the depth filtration media, the filtration efficiency and the filtration resistance of the fabric structure were improved when the filter pore size and the fiber diameter were smaller in magnitude. For all the five filter media, smaller the pore size of the filter media, greater was the filtration precision (for fine particles, such as PM2.5) of the fabric structure. In the dynamic filtration performance experiments, the filter pore size and the fiber diameter of the depth filtration media affected the dynamic filtration resistance and the dynamic filtration efficiency of the depth filtration media by affecting the deposition rate of dust in the depth filtration media; however, the filter pore size of the surface filtration media affected the blocking rate of dust in the membrane micropores, thus influencing the dynamic filtration resistance and the dynamic filtration efficiency of the surface filtration media.


Knockdown of miR-128a induces Lin28a expression and reverts myeloid differentiation blockage in acute myeloid leukemia.
Lin28A is a highly conserved RNA-binding protein that concurs to control the balance between stemness and differentiation in several tissue lineages. Here, we report the role of miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia (AML), a genetically heterogeneous disease characterized by abnormally controlled proliferation of myeloid progenitor cells accompanied by partial or total inability to undergo terminal differentiation. First, we found Lin28A underexpressed in blast cells from AML patients and AML cell lines as compared with CD34+ normal precursors. In vitro transfection of Lin28A in NPM1-mutated OCI-AML3 cell line significantly triggered cell-cycle arrest and myeloid differentiation, with increased expression of macrophage associate genes (EGR2, ZFP36 and ANXA1). Furthermore, miR-128a, a negative regulator of Lin28A, was found overexpressed in AML cells compared with normal precursors, especially in acute promyelocytic leukemia (APL) and in 'AML with maturation' (according to 2016 WHO classification of myeloid neoplasms and acute leukemia). Its forced overexpression by lentiviral infection in OCI-AML3 downregulated Lin28A with ensuing repression of macrophage-oriented differentiation. Finally, knockdown of miR-128a in OCI-AML3 and in APL/AML leukemic cells (by transfection and lentiviral infection, respectively) induced myeloid cell differentiation and increased expression of Lin28A, EGR2, ZFP36 and ANXA1, reverting myeloid differentiation blockage. In conclusion, our findings revealed a new mechanism for AML differentiation blockage, suggesting new strategies for AML therapy based upon miR-128a inhibition.


mTOR signaling-related MicroRNAs and Cancer involvement.
MicroRNAs (miRNAs) are a class of single-stranded RNAs, 18-23 nucleotides in length that regulate gene expression at the post-transcriptional level. Dysregulation of miRNAs has been closely associated with the development of cancer. In the process of tumorigenesis, mammalian target of rapamycin (mTOR) plays important roles, and the mTOR signaling pathway is aberrant in various types of human cancers, including non-small cell lung cancer (NSCLC), breast cancer, prostate cancer, as well as others. However, the relationship between miRNAs and the mTOR signaling pathway is indistinct. Herein, we not only summarize the progress of miRNAs and the mTOR signaling pathway in cancers, but also highlight their role in the diagnosis and treatment in the clinic.


A modified automated method for isolation of viable pancreatic islets in laboratory animals.
To achieve successful islet transplantation, a high viability is required. For this reason an automated method including two chambers: one for islets isolation and one for recirculation and collection was developed. Recently, we produced a modified version of this work by building a similar system of glass where marbles were not used for disaggregation, and the pancreatic tissue had to be disrupted mechanically before the digestion phase. By using the reconfigured system, we obtained 260 +/- 20 islets from each Wistar albino rat (weighing 220 to 240 g) pancreas. Islets were observed at 35 minutes after the start of perfusion (closed circuit) and the optimum time to stop the isolation determined to be 40 minutes based upon islets viability. Although the present system is configured for islet isolation from small laboratory animals (rat, mouse), we have also obtained thousands of islets at 25 minutes after treatment of a 0.5-g piece of pig pancreas. Compared to the time-consuming manual method usually used for islet isolation from small laboratory animals, the new technique is economic, easy to use, and does not reduce islets viability.


Peripancreatic paraganglioma mimics pancreatic/gastrointestinal neuroendocrine tumor on fine needle aspiration: Report of two cases and review of the literature.
Cytologic diagnosis of extra-adrenal paraganglioma presenting as a peripancreatic mass is challenging with a high error rate due to its rarity. We report two cases of peripancreatic masses identified by radiology. Endoscopic ultrasound-guided fine needle aspiration (FNA) of the masses showed a moderately cellular tumor composed of small to medium sized neoplastic cells with round to oval nuclei, arranged singly and in loose clusters. Focal rosette-like structures were present. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin). A diagnosis of a neoplasm with neuroendocrine differentiation and neuroendocrine tumor was made respectively on FNA for each case. The subsequent surgical resection of the tumors revealed peripancreatic paraganglioma. Although paraganglioma has been reported in the literature, the detailed comparison of perpancreatic paraganglioma versus pancreatic/gastrointestinal neuroendocrine tumor is still lacking. Therefore using these two cases with literature review, we wish to illustrate the differential diagnosis between these two entities based on cytomorphology and immunohistochemical study.


Efficiency of instant messaging applications in coordination of emergency calls for combat injuries: A pilot study.
Coordination of an emergency response team is an important determinant of prompt treatment for combat injuries in hospitals. The authors hypothesized that instant messaging applications for smartphones could be appropriate tools for notifying emergency response team members. The objective of this study was to investigate the efficiency of a commercial instant messaging application (WhatsApp, Mountain View, CA) as a communication tool for the emergency team in a level-I trauma center. We retrospectively evaluated the messages in the instant messaging application group that was formed to coordinate responses to patients who suffered from combat injuries and who were transported to our hospital via helicopter during an 8-week period. We evaluated the response times, response time periods during or outside of work hours, and the differences in the response times of doctors, nurses, and technicians among the members of the emergency team to the team leader's initial message about the patients. A total of 510 emergency call messages pertaining to 17 combat injury emergency cases were logged. The median time of emergency response was 4.1 minutes, 6 minutes, and 5.3 minutes for doctors, nurses, and the other team members, respectively. The differences in these response times between the groups were statistically significant (p=0.03), with subgroup analyses revealing significant differences between doctors and nurses (p=0.038). However, no statistically significant differences were observed between the doctors and the technicians (p=0.19) or the nurses and the technicians (p=1.0). From the team leader's perspective, using this application reduced the workload and the time loss, and also encouraged the team. Instant messaging applications for smartphones can be efficient, easy-to-operate, and time-saving communication tools in the transfer of medical information and the coordination of emergency response team members in hospitals.


Reconstruction of the pelvic ring after total en bloc sacrectomy using a 3D-printed sacral endoprosthesis with re-establishment of spinopelvic stability: a retrospective comparative study.
The aim of this study was to describe the use of 3D-printed sacral endoprostheses to reconstruct the pelvic ring and re-establish spinopelvic stability after total en bloc sacrectomy (TES) and to review its outcome. We retrospectively reviewed 32 patients who underwent TES in our hospital between January 2015 and December 2017. We divided the patients into three groups on the basis of the method of reconstruction: an endoprosthesis group (n = 10); a combined reconstruction group (n = 14), who underwent non-endoprosthetic combined reconstruction, including anterior spinal column fixation; and a spinopelvic fixation (SPF) group (n = 8), who underwent only SPF. Spinopelvic stability, implant survival (IS), intraoperative haemorrhage rate, and perioperative complication rate in the endoprosthesis group were documented and compared with those of other two groups. The mean overall follow-up was 22.1 months (9 to 44). In the endoprosthesis group, the mean intraoperative hemorrhage was 3530 ml (1600 to 8100). Perioperative complications occurred in two patients; both had problems with wound healing. After a mean follow-up of 17.7 months (12 to 38), 9/10 patients could walk without aids and 8/10 patients were not using analgesics. Imaging evidence of implant failure was found in three patients, all of whom had breakage of screws and/or rods. Only one of these, who had a local recurrence, underwent re-operation, at which solid bone-endoprosthetic osseointegration was found. The mean IS using re-operation as the endpoint was 32.5 months (95% confidence interval 23.2 to 41.8). Compared with the other two groups, the endoprosthesis group had significantly better spinopelvic stability and IS with no greater intraoperative haemorrhage or perioperative complications. The use of 3D-printed endoprostheses for reconstruction after TES provides reliable spinopelvic stability and IS by facilitating osseointegration at the bone-implant interfaces, with acceptable levels of haemorrhage and complications. Cite this article: Bone Joint J 2019;101-B:880-888.


Detection of necrosis of the gastric fundus after blunt abdominal trauma by PET-CT.
Positron emission tomography with [(18)F]-fluorodeoxyglucose provides functional and anatomic information by visualising the uptake of radiolabelled glucose in tumour and inflammatory cells. We report delayed diagnosis of necrosis of the gastric fundus after blunt abdominal trauma in a 73-year-old man. After a car accident with head-on collision, the patient was stabilised in our emergency room. His femur was treated by internal fixation, his ellbow was stabilised by a fixateur externe. During surgery his status deteriorated. The patient was in need of high dosage of inotrops during the following days. He had a biventricular pacemaker implanted because of ischemic myocardiopathy, and he suffered from renal insufficiency. Over the next days, his haemodynamics improved. A central venous line had to be removed because of ensuing septic fever. The patient complained of upper abdominal pain and nausea. A sonography and computer tomography without contrast medium were performed with negative result. Because of contamination of the central venous line with Staphylococcus epidermidis the pacemaker was evaluated for infection by transoesophageal echocardiography, again without any findings. Because of ongoing fever and positive inflammatory markers a positron emission tomography was indicated, as a contrast examination and a magnetic resonance examination were not feasible because of the renal insufficiency and the pacemaker, respectively. Prophylactic removal of the pacemaker would have been a substantial risk for the patient due to his underlying myocardiopathy. Positron emission tomography showed an increased tracer uptake in the gastric fundus, which turned out to be necrotic by endoscopy. A laparoscopic resection followed, and drainage of an abscess, which had evolved subsequently between stomach and spleen stopped the inflammatory process. This case report demonstrates that positron emission tomography may be an alternative to computer tomography with contrast medium and magnetic resonance imaging to detect an inflammatory process in patients with pre-existing disease.


An outbreak of gentamicin-resistant Klebsiella pneumoniae: analysis of control measures.
In April 1978, a strain of gentamicin-resistant Klebsiella pneumoniae (GRK) was introduced into the neonatal intensive care unit of Henry Ford Hospital. An additional ten cases of GRK occurred over the subsequent 16 months and intestinal colonization occurred in up to 91% of admissions per month. All GRK were susceptible to amikacin and were capsular serotype 19. Though hand contamination of hospital personnel with GRK was documented, increased handwashing practices did not reduce colonization rates of neonates with the epidemic strain. Intestinal carriage persisted for up to ten months and could not be eradicated by administering oral colistin sulfate. Discontinuation of gentamicin and utilization of amikacin were associated with a significant reduction in colonization with GRK (p less than 0.05). However, the only control measure that prevented both new cases and colonization with the epidemic strain was the utilization of a strict cohort system.


A revised dated phylogeny of scorpions: Phylogenomic support for ancient divergence of the temperate Gondwanan family Bothriuridae.
The scorpion family Bothriuridae occupies a subset of landmasses formerly constituting East and West temperate Gondwana, but its relationship to other scorpion families is in question. Whereas morphological data have strongly supported a sister group relationship of Bothriuridae and the superfamily Scorpionoidea, a recent phylogenomic analysis recovered a basal placement of bothriurids within Iurida, albeit sampling only a single exemplar. Here we reexamined the phylogenetic placement of the family Bothriuridae, sampling six bothriurid exemplars representing both East and West Gondwana, using transcriptomic data. Our results demonstrate that the sister group relationship of Bothriuridae to the clade ("Chactoidea" + Scorpionoidea) is supported by the inclusion of additional bothriurid taxa, and that this placement is insensitive to matrix completeness or partitioning by evolutionary rate. We also estimated divergence times within the order Scorpiones using multiple fossil calibrations, to infer whether the family Bothriuridae is sufficiently old to be characterized as a true Gondwanan lineage. We show that scorpions underwent ancient diversification between the Devonian and early Carboniferous. The age interval of the bothriurids sampled (a derived group that excludes exemplars from South Africa) spans the timing of breakup of temperate Gondwana.


Evaluation of immunological indices in HIV-infected patients with chronic hepatitis C in Kazakhstan.
To evaluate immunological indices in HIV-infected patients with chronic hepatitis C (CHC) who are injecting drug users. The study examined 38 patients coinfected with HIV and CHC who were injecting drug users and 36 patients with HIV/CHC who were not injecting drug users. In the study of immune status, the relative and absolute numbers of CD3+, CD4+, CD8+, CD16+, and CD20+ cells were determined by means of flow cytofluorometry of "FACSCount" using monoclonal antibodies of the company Becton Dickinson. The level of circulating immune complexes in blood serum was determined by means of precipitation in polyethylene glycol solution. It was found that T-cell immunodeficiency was developing in patients coinfected with HIV and CHC. T-cell immunodeficiency was characterized by a decrease in the number of T-helpers, mainly for injecting drug users. At the same time, patients coinfected with HIV and CHC experienced markedly elevated levels of circulating immune complexes, mainly among injecting drug users. The evaluation of immunogram indices in injecting drug users coinfected with HIV and CHC, depending on the stage of HIV infection, revealed a greater degree of immune-suppression of T-helper cells in clinical stage III. Our comprehensive immunological study of patients coinfected with HIV and CHC revealed a pronounced dysfunction of the immune system. The comparison of the immune system indices in patients with HIV/CHC showed a more pronounced T-cell suppression in injecting drug users than in patients with HIV/CHC but who were not injecting drug users.


Gastrointestinal smooth muscle tumors and iron deficiency anemia in children.
Smooth muscle tumors are rarely seen in the pediatric population. We present a child with smooth muscle tumor of low malignant potential in the ileocecal valve region in whom iron deficiency anemia was the only presenting sign. Abdominal computed tomographic (CT) scan, barium enema, and colonoscopy revealed the mass. Following resection of the tumor the anemia was corrected and the child feels well.


Seizure disorder as a risk factor for gastroesophageal reflux in children with neurodevelopmental disabilities.
The proportion of children with severe neurodevelopmental disabilities, in whom symptoms of gastroesophageal reflux develop after gastrostomy placement, has not been well studied. The medical records of children who received a gastrostomy tube (with or without a simultaneous antireflux procedure) at our institution between 1987 and 1997 were reviewed to identify neurologically related diagnoses at the time of the gastrostomy, diagnostic tests ordered to detect reflux, and dates and reasons for re-admissions within 2 years of discharge. Of 102 patients studied, 37 received a gastrostomy tube alone. Complete follow-up data were available for 30 of these patients, 7 of whom (23%) required subsequent antireflux surgery within 2 years. Patients with a seizure disorder had greater than a 4-fold risk of re-admission for this operation compared with other patients (57% [4/7] vs. 13% [3/23]; P=0.03). In a child with severe neurodevelopmental disability, the existence of a seizure disorder at the time of a gastrostomy operation increases the risk of subsequently requiring an antireflux procedure by a factor of 4.


Cysteine-containing peptide sequences exhibit facile uncatalyzed transacylation and acyl-CoA-dependent acylation at the lipid bilayer interface.
A variety of simple cysteine-containing lipopeptides, with sequences modeled on those found in naturally occurring S-acylated proteins, undergo spontaneous S-acylation in phospholipid vesicles at physiological pH when either long-chain acyl-CoAs or other S-acylated peptides are added as acyl donors. Fluorescent or radiolabeled lipopeptides with the sequence myristoyl-GCX- (X = G, L, R, T, or V), a motif found to undergo S-acylation in several intracellular regulatory proteins, and the prenylated peptide -SCRC(farnesyl)-OMe, modeled on the carboxyl terminus of p21H-ras, were all found to be suitable acyl acceptors for such uncatalyzed S-acyl transfer reactions at physiological pH. Acylation of these cysteinyl-containing lipopeptides to high stoichiometry was observed, on time scales ranging from a few hours to a few tens of minutes, in vesicles containing relatively low concentrations (< or = mol %) and only a modest molar excess (2.5:1) of the acyl donor species. No evidence was obtained for acyl transfer to peptide serine or threonine hydroxyl groups under the same conditions. These observations may have significant implications both for the design of in vitro studies of the S-acylation of membrane-associated proteins and for our understanding of the mechanisms of S-acylation of these species in vivo.


A Longitudinal Study on Attention Development in Primary School Children with and without Teacher-Reported Symptoms of ADHD.
Background: Prospective longitudinal studies are essential in characterizing cognitive trajectories, yet few of them have been reported on the development of attention processes in children. We aimed to explore attention development in normal children and children with attention deficit and hyperactivity disorder (ADHD) symptoms in a repeated measures design using the attention network test (ANT). Methods: The population sample included 2,835 children (49.6% girls) aged 7-11 years from 39 schools in Barcelona (Catalonia, Spain) who performed the ANT four times from January 2012 to March 2013. According to teacher ratings, 10.5% of the children presented ADHD symptoms. We performed multilevel mixed-effects linear regression models, adjusting for school and individual, to test the effects of age-related growth on the ANT networks: alerting, orienting and executive attention, and three measurements related to attentiveness: median of hit reaction time (HRT), hit reaction time standard error (HRT-SE) and variability. Results: We observed age-related growth in all the outcomes, except orienting. The curves were steeper at the younger groups, although for alertness the improvement was further at the oldest ages. Gender and ADHD symptoms interacted with age in executive attention, HRT and variability. Girls performed better in executive attention at young ages although boys reached females at around 10 years of age. For HRT, males showed faster HRT. However, girls had a more pronounced improvement and reached the levels of boys at age 11. Children with ADHD symptoms had significant differences in executive attention, HRT and variability compared to children without ADHD symptoms. Conclusions: We detected an ongoing development of some aspects of attention in primary school children, differentiating patterns by gender and ADHD symptoms. Our findings support the ANT for assessing attention processes in children in large epidemiological studies.


Application of mentorship program for another aspect of surgical residency training: The importance of academia in surgical training.
Traditionally, surgical residency training is more focused on obtaining surgical skills through a well-established coaching system worldwide. However, constant advances in medical science require surgeons to learn not only surgical skills but also the ability of scientific research to improve clinical practice and future professional development. The study aims to emphasize that professional education in terms of scientific research is also significant for surgical residency training.All residents who had been recruited in a medical center for the surgery residency program between years 2006 and 2015 were evaluated in the study. Generally, every resident is assigned to a mentor since the first year of residency. Then, the mentor would help the resident qualify a 2-step evaluation in terms of scientific research during the residency training program.A total of 193 residents were evaluated in the study. All of them had completed the first step regarding oral presentation of their designated research, and the majority of residents obtained 80 to 90 points that were rated by referees. Overall, 102 residents (52.8%) had completed the second step with the publication of a research manuscript. The percentage of residents who had fulfilled the criteria of this 2-step assessment ranged from 35.3% to 81.8% by year.The continuing education for surgical residents should not be limited in coaching clinical practice. Scientific research is also essential for current surgical residency training, and a formal mentorship program may be beneficial for the future professional development of surgical residents. However, the success of the 2-step evaluation could possibly depend on the career choices of the residents instead of the mentorship program.


The MRN-CtIP pathway is required for metaphase chromosome alignment.
Faithful duplication of the genome in S phase followed by its accurate segregation in mitosis is essential to maintain genomic integrity. Recent studies have suggested that proteins involved in DNA transactions are also required for whole-chromosome stability. Here we demonstrate that the MRN (Mre11, Rad50, and Nbs1) complex and CtIP are required for accurate chromosome segregation. Depletion of Mre11 or CtIP, antibody-mediated inhibition of Mre11, or small-molecule inhibition of MRN using mirin results in metaphase chromosome alignment defects in Xenopus egg extracts. Similarly, loss of MRN function adversely affects spindle assembly around DNA-coated beads in egg extracts. Inhibition of MRN function in mammalian cells triggers a metaphase delay and disrupts the RCC1-dependent RanGTP gradient. Addition of the Mre11 inhibitor mirin to egg extracts and mammalian cells reduces RCC1 association with mitotic chromosomes. Thus, the MRN-CtIP pathway contributes to Ran-dependent mitotic spindle assembly by modulating RCC1 chromosome association.


Gaze Strategies in Driving-An Ecological Approach.
Human performance in natural environments is deeply impressive, and still much beyond current AI. Experimental techniques, such as eye tracking, may be useful to understand the cognitive basis of this performance, and "the human advantage." Driving is domain where these techniques may deployed, in tasks ranging from rigorously controlled laboratory settings through high-fidelity simulations to naturalistic experiments in the wild. This research has revealed robust patterns that can be reliably identified and replicated in the field and reproduced in the lab. The purpose of this review is to cover the basics of what is known about these gaze behaviors, and some of their implications for understanding visually guided steering. The phenomena reviewed will be of interest to those working on any domain where visual guidance and control with similar task demands is involved (e.g., many sports). The paper is intended to be accessible to the non-specialist, without oversimplifying the complexity of real-world visual behavior. The literature reviewed will provide an information base useful for researchers working on oculomotor behaviors and physiology in the lab who wish to extend their research into more naturalistic locomotor tasks, or researchers in more applied fields (sports, transportation) who wish to bring aspects of the real-world ecology under experimental scrutiny. Part of a Research Topic on Gaze Strategies in Closed Self-paced tasks, this aspect of the driving task is discussed. It is in particular emphasized why it is important to carefully separate the visual strategies driving (quite closed and self-paced) from visual behaviors relevant to other forms of driver behavior (an open-ended menagerie of behaviors). There is always a balance to strike between ecological complexity and experimental control. One way to reconcile these demands is to look for natural, real-world tasks and behavior that are rich enough to be interesting yet sufficiently constrained and well-understood to be replicated in simulators and the lab. This ecological approach to driving as a model behavior and the way the connection between "lab" and "real world" can be spanned in this research is of interest to anyone keen to develop more ecologically representative designs for studying human gaze behavior.