Stiffness mapping of lower leg muscles during passive dorsiflexion.
It is challenging to differentiate the mechanical properties of synergist muscles in vivo. Shear wave elastography can be used to quantify the shear modulus (i.e. an index of stiffness) of a specific muscle. This study assessed the passive behavior of lower leg muscles during passive dorsiflexion performed with the knee fully extended (experiment 1, n = 22) or with the knee flexed at 90° (experiment 2, n = 20). The shear modulus measurements were repeated twice during experiment 1 to assess the inter-day reliability. During both experiments, the shear modulus of the following plantar flexors was randomly measured: gastrocnemii medialis (GM) and lateralis (GL), soleus (SOL), peroneus longus (PL), and the deep muscles flexor digitorum longus (FDL), flexor hallucis longus (FHL), tibialis posterior (TP). Two antagonist muscles tibialis anterior (TA), and extensor digitorum longus (EDL) were also recorded. Measurements were performed in different proximo-distal regions for GM, GL and SOL. Inter-day reliability was adequate for all muscles (coefficient of variation < 15%), except for TP. In experiment 1, GM exhibited the highest shear modulus at 80% of the maximal range of motion (128.5 ± 27.3 kPa) and was followed by GL (67.1 ± 24.1 kPa). In experiment 2, SOL exhibited the highest shear modulus (55.1 ± 18.0 kPa). The highest values of shear modulus were found for the distal locations of both the GM (80% of participants in experiment 1) and the SOL (100% of participants in experiment 2). For both experiments, deep muscles and PL exhibited low levels of stiffness during the stretch in young asymptomatic adults, which was unknown until now. These results provide a deeper understanding of passive mechanical properties and the distribution of stiffness between and within the plantar flexor muscles during stretching between them and thus could be relevant to study the effects of aging, disease progression, and rehabilitation on stiffness.


Patient Safety and Suitability for Primary Cleft Lip Repair as Day Case Surgery - A Systematic Review and Meta-Analysis.
To perform a systematic review and meta-analysis to determine if day case cleft lip surgery has an impact on complications and 30-day readmission rate. A systematic review was conducted using PRISMA guidelines. Databases included; PubMed, Science Direct, Ovid and Cochrane. Search terms; "Day Case", "Day Care", "outpatient", "Ambulatory" AND "Cleft", "Cleft Lip". Meta-analysis was performed using RevMan 5. Eligible study types included; randomised controlled trials, observational studies (prospective and retrospective) and case series. Paediatric patients undergoing primary cleft lip repair. Day case surgery versus inpatient admission post-operative. Primary outcome measure: Primary cleft lip repair performed as a day case in paediatric patients. Secondary outcome measures: 1. Complication rates and 30-day re-admission to hospital rate. 2. Patient suitability for day case surgery. Ten papers with 13 804 patients undergoing primary cleft lip repair were included, 28% were discharged on the day of surgery (Range 17%-81%). There was no significant difference in complication rate between the inpatient and day case cohorts. There was a significant reduction in 30-day readmission rates in the day case cohort. This meta-analysis indicates there is no difference in complication rates for patients discharged on the day of surgery compared to those admitted overnight. Complications encountered were infrequent, non-life threatening and often occurred more than 24 h following discharge. There was an observed reduction in 30-day readmission rates for day-case patients. This is likely to represent a variation in baseline characteristics which deemed them suitable for day case surgery pre-operatively.


Severe chronic spontaneous urticaria in children - treatment options according to the guidelines and beyond - a 10 years review.
This is a retrospective study of 18 children with chronic spontaneous urticaria (CSU), where standard therapies, including up-dosing of antihistamines and omalizumab, were unable to cure the disease and where alternative strategies with experimental and off-label medication had to be used. Being aware that our questionnaire is validated only for elder children or adults, we utilized the UAS7 to monitor disease control with the help of the parents. The UAS7 score decreased from a mean of 25 to an average of 13 after 8 weeks of therapy in 13 patients. Five patients had no significant reduction of UAS7 by week 8. In two of five patients, where periodic improvement was seen, omalizumab therapy was continued and showed complete response after 1-2 years. In three children, alternative treatments with cyclosporine and dupilumab, approved by the ethics committee, showed symptom improvement from a mean UAS7 of 29 to a mean value of 6. When omalizumab therapy including up-dosing strategies or shortened interval shows no symptom improvement, alternative therapies, sometimes off-label have to be considered in time.


Ultrasonographic evaluation of effectiveness of circumoral muscle exercises in adenotonsillectomized children.
Mouth breathing due to obstructive adenoids and tonsils has deleterious effects on craniofacial morphology especially on dentition and dental arches. Reports confirm that removal of nasal obstruction, adenoids and tonsils has not given beneficial development of circumoral musculature. Use of muscles to correct malocclusion was first recommended by Alfred Paul Rogers. This study highlights the imaging of circumoral musculature using ultrasound to evaluate the effectiveness of muscle exercises in adenotonsillectomized children. Definite changes in muscle thickness were noted in subjects, who were given muscle exercises.


Water at hydrophobic interfaces delays proton surface-to-bulk transfer and provides a pathway for lateral proton diffusion.
Fast lateral proton migration along membranes is of vital importance for cellular energy homeostasis and various proton-coupled transport processes. It can only occur if attractive forces keep the proton at the interface. How to reconcile this high affinity to the membrane surface with high proton mobility is unclear. Here, we tested whether a minimalistic model interface between an apolar hydrophobic phase (n-decane) and an aqueous phase mimics the biological pathway for lateral proton migration. The observed diffusion span, on the order of tens of micrometers, and the high proton mobility were both similar to the values previously reported for lipid bilayers. Extensive ab initio simulations on the same water/n-decane interface reproduced the experimentally derived free energy barrier for the excess proton. The free energy profile G(H(+)) adopts the shape of a well at the interface, having a width of two water molecules and a depth of 6 ± 2RT. The hydroniums in direct contact with n-decane have a reduced mobility. However, the hydroniums in the second layer of water molecules are mobile. Their in silico diffusion coefficient matches that derived from our in vitro experiments, (5.7 ± 0.7) 10(-5) cm(2) s(-1). Conceivably, these are the protons that allow for fast diffusion along biological membranes.


Analyzing X-ray tomographies of granular packings.
Starting from three-dimensional volume data of a granular packing, as, e.g., obtained by X-ray Computed Tomography, we discuss methods to first detect the individual particles in the sample and then analyze their properties. This analysis includes the pair correlation function, the volume and shape of the Voronoi cells, and the number and type of contacts formed between individual particles. We mainly focus on packings of monodisperse spheres, but we will also comment on other monoschematic particles such as ellipsoids and tetrahedra. This paper is accompanied by a package of free software containing all programs (including source code) and an example three-dimensional dataset which allows the reader to reproduce and modify all examples given.


[Preparation of Cervical Dilatation Before with Misoprostol and Laminaria - Advantages and Disadvantages.]
The surgical hysteroscopy became popular as a minimally invasive approach to interuterine changes. Dilatation is a real challenge during surgical hyseroscopy especially in first delivery patients, women in menopause and women with cervical stenosis. Apart from this, some long hysteroscopy operations such as myomectomy require adequate dilatation in order to facilitate the multiple insertions and drawing pulling of the resectoscope. Another technical problem is the need for a significant degree of cervical dilatation, as well as softening of the cervix, which will allow the extraction of the excised endometrial polyps or myomatose parts. Mysoprostol is analogous to prostaglandin El, which is commonly used in obstetrics to induce an abortion and birth, as well as after birth to control the excessive vaginal bleeding. Its use in gynecology is limited. In our study it is of vital importance. The vaginal administration of MysoproStol before surgical hysteroscopy facilitates dilatation. The eased hysteroscopy minimizes cervical complications. On the other hand, the natural dilatators Laminaria, made of Laminariajaponica orLaminaria Digitata sticks, are attractive natural substances which can cause dilatation with minimally observed systemic side effects. They have shown efficient results during the cervical preparation before surgical hysteroscopy. Despite of that, there are no comparative studies on the efficiency of the two methods for cervical preparation. The aim of this Study is to compare the efficacy of internally vaginal Mysoprostol against endocervical dilatators Laminaria before surmical hvSterosconv in certain cases.


Five-year follow-up of a randomized multicenter trial of intensive early intervention vs standard treatment for patients with a first episode of psychotic illness: the OPUS trial.
Intensive early treatment for first-episode psychosis has been shown to be effective. It is unknown if the positive effects are sustained for 5 years. To determine the long-term effects of an intensive early-intervention program (OPUS) for first-episode psychotic patients. Single-blinded, randomized, controlled clinical trial of 2 years of an intensive early-intervention program vs standard treatment. Follow-up periods were 2 and 5 years. Copenhagen Hospital Corporation and Psychiatric Hospital, Aarhus, Denmark. Patients A total of 547 patients with a first episode of psychosis. Of these, 369 patients were participating in a 2-year follow-up, and 301 were participating in a 5-year follow-up. A total of 547 patients were followed for 5 years. Two years of an intensive early-intervention program vs standard treatment. The intensive early-intervention treatment consisted of assertive community treatment, family involvement, and social skills training. Standard treatment offered contact with a community mental health center. Psychotic and negative symptoms were recorded. Secondary outcome measures were use of services and social functioning. Analysis was based on the principles of intention-to-treat. Assessment was blinded for previous treatment allocation. At the 5-year follow-up, the effect of treatment seen after 2 years (psychotic dimension odds ratio [OR], -0.32; 95% confidence interval [CI], -0.58 to -0.06; P = .02; negative dimension OR, -0.45; 95% CI, -0.67 to -0.22; P = .001) had equalized between the treatment groups. A significantly smaller percentage of patients from the experimental group were living in supported housing (4% vs 10%, respectively; OR, 2.3; 95% CI, 1.1-4.8; P = .02) and were hospitalized fewer days (mean, 149 vs 193 days; mean difference, 44 days; 95% CI, 0.15-88.12; P = .05) during the 5-year period. The intensive early-intervention program improved clinical outcome after 2 years, but the effects were not sustainable up to 5 years later. Secondary outcome measures showed differences in the proportion of patients living in supported housing and days in hospital at the 5-year follow-up in favor of the intensive early-intervention program.


Solitary intraductal papilloma of the breast--a diagnostic dilemma and the role of conferencing between surgeons and cytologist.
A 40 year female, presented with the complaints of spontaneous, sticky, blood stained discharge from the nipple of the left breast since 6 months. On examination there was no lump palpable in either breast. Cytology of the nipple discharge (ND) showed scanty cellularity consisting of tight papillary clusters of ductal cells in a hemorrhagic and inflammatory background. The nuclei were bland and showed degenerative atypia. Mammography showed no significant lesion. Our patient underwent microdochechtomy. Histopathology showed intraductal papilloma. Limitations of cytology must be kept in mind by both, the pathologist and the surgeon. The cytological diagnosis of a papillary tumor is provisional and the definitive diagnosis must await histological examination. In view of rarity of this lesion, combined with the overlapping of cytologic features in benign and malignant papillary lesions, conferencing and communication with the surgeon should be an integral part of patient evaluation and management. In our case this approach resulted in less radical excision of breast tissue.


Effect of diode lasers with wavelength of 445 and 980 nm on a temperature rise when uncovering implants for second stage surgery: An ex-vivo study in pigs.
Many surgical procedures in soft tissue are performed using diode lasers. Recently, a novel diode laser operating at 445 nm wavelength was introduced in dentistry. The aim of our study was to evaluate the time of surgery and an increase in temperature of titanium implants during its uncovering using 445 and 980 nm wavelengths. The research included 45 pig mandibles (n = 45). The specimens were randomly divided into 3 groups (n = 15) according to the laser irradiation mode and wavelength; G1 - 445 nm laser, power: 3 W, continuous wave (CW), distance: 2 mm, power density: 7460 W/cm2, fiber: 320 μm, noncontact mode; G2 - 445 nm laser (power: 2 W, CW, power density: 4970 W/cm2, fiber: 320 μm, contact mode; G3 (control) - 980 nm laser, power: 2.5 W, CW, power density: 15920 W/cm2, fiber: 200 μm, contact mode. The temperature was measured with a 2 K-type thermocouples (a P1 at collar and a P2 at mid height of the implant). The mean temperature rises measured by the P1 thermocouple were 16.9°C, 36.1°C and 21.6°C in the G1, G2 and G3 group, respectively. Significant differences in temperature rise were found between the G1 and G2 group (p = 0.0007) and the G2 and G3 group (p = 0.01). The mean temperature rises measured by the P2 thermocouple were 1.8°C, 1.4°C and 5.6°C in the G1, G2 and G3 group, respectively. Significant differences in temperature rise were found between the G1 and the G2 or G3 group (p = 0.0001). The significant differences among the study groups in average time necessary for uncovering the implants amounted to 69.7, 54.4 and 83.6 s, respectively (p < 0.05). The application of the 445 nm diode laser in non-contact mode reduced the temperature rise of the implants. The additional pulse intervals during laser irradiation with wavelength of 445 nm when operating in contact mode are needed.


Burst of succinate dehydrogenase and α-ketoglutarate dehydrogenase activity in concert with the expression of genes coding for respiratory chain proteins underlies short-term beneficial physiological stress in mitochondria.
Conditions for the realization in rats of moderate physiological stress (PHS) (30-120 min) were selected, which preferentially increase adaptive restorative processes without adverse responses typical of harmful stress (HST). The succinate dehydrogenase (SDH) and α-ketoglutarate dehydrogenase (KDH) activity and the formation of reactive oxygen species (ROS) in mitochondria were measured in lymphocytes by the cytobiochemical method, which detects the regulation of mitochondria in the organism with high sensitivity. These mitochondrial markers undergo an initial 10-20-fold burst of activity followed by a decrease to a level exceeding the quiescent state 2-3-fold by 120 min of PHS. By 30-60 min, the rise in SDH activity was greater than in KDH activity, while the activity of KDH prevailed over that of SDH by 120 min. The attenuation of SDH hyperactivity during PHS occurs by a mechanism other than oxaloacetate inhibition developed under HST. The dynamics of SDH and KDH activity corresponds to the known physiological replacement of adrenergic regulation by cholinergic during PHS, which is confirmed here by mitochondrial markers because their activity reflects these two types of nerve regulation, respectively. The domination of cholinergic regulation provides the overrestoration of expenditures for activity. In essence, this phenomenon corresponds to the training of the organism. It was first revealed in mitochondria after a single short-time stress episode. The burst of ROS formation was congruous with changes in SDH and KDH activity, as well as in ucp2 and cox3 expression, while the activity of SDH was inversely dependent on the expression of the gene of its catalytic subunit in the spleen. As the SDH activity enhanced, the expression of the succinate receptor decreased with subsequent dramatic rise when the activity was becoming lower. This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaption and therapy.


Streptobacillus notomytis sp. nov., isolated from a spinifex hopping mouse (Notomys alexis Thomas, 1922), and emended description of Streptobacillus Levaditi et al. 1925, Eisenberg et al. 2015 emend.
A pleomorphic, Gram-negative, rod-shaped, indole-, oxidase- and catalase-negative, non-spore-forming, non-motile bacterium was isolated in 1979 from the heart of a spinifex hopping mouse (Notomys alexis Thomas, 1922) with septicaemia and stored as Streptobacillus moniliformis in the strain collection of the Animal Health Laboratory, South Perth, Western Australia (AHL 370-1), as well as under CCUG 12425. On the basis of 16SrRNA gene sequence analyses, the strain was assigned to the genus Streptobacillus, with 99.4 % sequence similarity to the type strain of Streptobacillus moniliformis, 95.6 %sequence similarity to the type strain of Streptobacillus hongkongensis and 99.0 %sequence similarity to the type strain of Streptobacillus felis. The clear differentiation of strain AHL 370-1T from Streptobacillus moniliformis, Streptobacillus hongkongensis and Streptobacillus felis was also supported by rpoB, groEL and recA nucleotide and amino acid sequence analysis. Average nucleotide identity was 87.16 % between strain AHL 370-1T and Streptobacillus moniliformis DSM 12112T. Physiological data confirmed the allocation of strain AHL 370-1T to the family Leptotrichiaceae, considering the very similar profiles of enzyme activities and fatty acids compared to closely related species. Within the genus Streptobacillus,isolate AHL 370-1T could also be separated unambiguously from the type strains of Streptobacillus moniliformis, Streptobacillus hongkongensis and Streptobacillus felis by MALDI-TOF mass spectrometry. Two further strains (KWG2 and KWG24) isolated from asymptomatic black rats in Japan were highly similar to AHL 370-1T. On the basis of these data, we propose the novel species Streptobacillus notomytis sp. nov., with the type strain AHL370-1T (=CCUG 12425T=DSM 100026T=CCM 8593T=EF 12425T).


Band Structure Simulations of the Photoinduced Changes in the MgB₂:Cr Films.
An approach for description of the photoinduced nonlinear optical effects in the superconducting MgB₂:Cr₂O₃ nanocrystalline film is proposed. It includes the molecular dynamics step-by-step optimization of the two separate crystalline phases. The principal role for the photoinduced nonlinear optical properties plays nanointerface between the two phases. The first modified layers possess a form of slightly modified perfect crystalline structure. The next layer is added to the perfect crystalline structure and the iteration procedure is repeated for the next layer. The total energy here is considered as a varied parameter. To avoid potential jumps on the borders we have carried out additional derivative procedure.


The Association Between Cardio-Ankle Vascular Index and Primary Idiopathic Complete Atrioventricular Block in an Elderly Population.
The most common cause of complete atrioventricular block (CAVB) is age-related fibrotic degeneration and is referred to as primary idiopathic complete atrioventricular block (iCAVB). This study aims to investigate the relationship between iCAVB and arterial stiffness using the cardio-ankle vascular index (CAVI).In this study, of 205 CAVB patients, 41 patients with iCAVB implanted with a dual-chamber permanent pacemaker and 40 age- and gender-matched controls were studied. Arterial stiffness was assessed by a VaSera VS-1000 CAVI instrument. The CAVI values of patients with iCAVB were significantly higher compared with the controls (9.63 ± 1.42 vs 8.57 ± 1.12, P < .001). Idiopathic complete atrioventricular block frequency was higher among patients with abnormal CAVI values than those with borderline and normal CAVI (P = .04). In multivariate analysis, only CAVI was an independent predictor of iCAVB after adjusting for other relevant factors (odds ratio, 2.575; 95% CI [1.390-4.770]; P = .003). The present study demonstrated that CAVI, as a marker of arterial stiffness, was increased among elderly patients with iCAVB. Thus, we provide a possible additional mechanism linking easily measured CAVI with iCAVB.


Prediction of upper limb recovery, general disability, and rehabilitation status by activity measurements assessed by accelerometers or the Fugl-Meyer score in acute stroke.
This study investigated the clinical predictive value of the Fugl-Meyer Assessment (FMA) arm score and the upper limb activity assessed by accelerometers in patients with hemiparesis after acute stroke. The prospective cohort (n = 129) was recruited from a general hospital; activity variables and FMA score at intake were related to the FMA, the modified Rankin Scale, and rehabilitation status after 3 mos of follow-up. The prediction model was based on binary logistic regression. Although the FMA score at intake has the best overall predictive value for all three outcome measures (FMA3, 87.6%; modified Rankin Scale, 85.3%; RS, 73.6%), the activity of the impaired arm as assessed by the accelerometer has the best predictive value to determine patients who are at risk for continued disability (modified Rankin Scale score 1, 95.1%). The most difficult outcome measure for prediction is the rehabilitation status; specifically, the patients who went home are predicted imprecisely. The ratio variable is the least accurate predictor of all tested variables. The FMA arm score at intake is the best predictor for arm recovery and general disability. The activity of the impaired arm is an excellent predictor for prolonged disability and is an alternative to the FMA score when it is impossible to score the FMA in the acute phase of stroke.


Laboratory Culture of the Sepiolid Squid Euprymna scolopes: A Model System for Bacteria-Animal Symbiosis.
The small Hawaiian sepiolid Euprymna scolopes, with its symbiotic luminous bacterium Vibrio fischeri, was cultured through one complete life cycle in 4 months. Paralarval squid hatchlings were actively planktonic for the first 20-30 days, after which they settled and assumed the typical adult mode of nocturnal activity and diurnal quiescence. Squids were aggressive predators that preferred actively swimming prey up to 2-4 times their size; the only diet that yielded good survival and rapid growth for paralarvae was large adult mysids. Survival to settlement was 73% on this diet, whereas it was 0%-17% on controls and three other diets. Paralarvae initially lacked both detectable luminescence and V. fischeri cells in their incipient light organs; all remaining stages produced luminescence, and their light organs were colonized by apparently pure cultures of > 105 V. fischeri typical of E. scolopes symbiont strains. Survival from settlement to sexual maturity was 76%. Mating and egg laying commenced at 2 months, yet attempts to culture the next laboratory generation of hatchlings were not as successful. The results indicate that the host organism of this symbiosis can soon be cultured with consistency through its brief life cycle, thus opening new avenues of research into developmental aspects of this symbiosis.


[Analgesia and sedation in the pregnant patient].
Nonobstetric emergencies are frequent during pregnancy. The emergency physician must be knowledgeable regarding the physiological changes related to pregnancy, and must evaluate the benefit/risk ratio of any medication given to the mother. Though maternal side-effects are easy to predict, the fetal risk remains difficult to evaluate as medications are numerous and clinical evidence scarce. For analgesia as for sedation, the choice will depend on both the clinical context of the patient, the desired objective, and the assumed fetal risk.


Transcriptional regulation of E-cadherin and oncoprotein E7 by valproic acid in HPV positive cell lines.
Valproic acid (VPA) has proven to be as one of the most promising useful drug with anticancer properties. In this study, we investigate the VPA effects on E-cadherin expression in HeLa, TC1, MKN45, and HCT116 cell lines. This study assesses the effects of VPA on human papillomavirus E7 expression in HPV positive cell lines. Cell lines were treated by 2 mmol/l VPA and expression of E-cadherin and E7 was analyzed by quantitative real-time PCR. Student's t test and ANOVA were used to determine changes in expression levels. The results revealed that mean of E-cadherin expression is increased by VPA 1.8 times in HCT116 and MKN45 cell lines, also the mean of E-cadherin mRNA levels is up-regulated 2.9 times in HeLa and TC1 cell lines. So, E-cadherin augmentation induced by VPA in HeLa and TC-1, HPV positive cell lines, is higher than HPV negative cell lines MKN45 and HCT116. The mean of HPV E7 expression is decreased by VPA, 4.6 times in in HeLa and TC-1 cell lines. This study demonstrates that re-expression of E-cadherin by VPA in HPV positive cell lines is more than HPV negative cell lines. Whereas, HPV E7 reduces the expression of E-cadherin, reduction of HPV E7 expression by VPA is related to more augmentation of E-cadherin in HPV positive cell lines. So, this study demonstrates that VPA has more anticancer properties in HPV positive cell lines, and could potentially be a promising candidate for cervical cancer treatment.


Surface phase behavior in Gibbs monolayers of bis(ethylene glycol) mono-n-tetradecyl ether at the air-water interface.
We present the adsorption kinetics and surface morphology of the adsorbed monolayers of bis(ethylene glycol) mono-n-tetradecyl ether (C14E2) by film balance and Brewster angle microscopy. A cusp point followed by a plateau region in the pressure (pi)-time (t) adsorption isotherm indicates a first-order phase transition in the coexistence region between a lower density liquid expanded (LE) phase and a higher density liquid condensed (LC) phase. A variety of condensed phase domains surrounded by the homogeneous LE phase are observed just after the appearance of the phase transition. The domains are of a spiral or striplike structure at lower temperatures. This characteristic shape of the domains is because of strong dipole-dipole repulsion between the molecules. At 18 degrees C, the domains are found to be quadrant structures. A slight increase in subphase temperature (around 1 degrees C) brings about a quadrant-to-circular shape transition in the domains. The circular domains return to quadrant structures as the subphase temperature is lowered. The domains completely disappear when the temperature is increased beyond 19 degrees C, suggesting that the critical temperature for the condensed domain formation is 19 degrees C. Above this temperature, the hypothetical surface pressure necessary for the phase transition exceeds the actual surface pressure attainable from a solution of concentration greater than or equal to the critical micelle concentration. An increase in molecular motion with increasing temperature results in a higher degree of chain flexibility. As a result, the molecules cannot accumulate in the condensed phase form when the subphase temperature is above 19 degrees C.


Comparative cytogenetic mapping of rRNA genes among naked catfishes: implications for genomic evolution in the Bagridae family.
In the present study, the karyotype and chromosomal characteristics of 9 species of the Bagridae fish family were investigated using conventional Giemsa staining as well as dual-color fluorescence in situ hybridization to detect the 18S and 5S rDNA sites. In addition to describing the karyotype of several Bagridae catfishes, we established molecular cytogenetic techniques to study this group. The 9 species contained a diploid chromosomal number, varying from 50 (Pseudomystus siamensis) to 62 (Hemibagrus wyckii), while none contained heteromorphic sex chromosomes. 18S rDNA sites were detected in only 1 chromosomal pair among all species evaluated. However, 3 different patterns were observed for the distribution of the 5S rDNA: 2 sites were found in the genus Mystus and in P. siamensis, multiple sites were observed in the genus Hemibagrus, and a syntenic condition for the 18S and 5S rDNA sites was identified in H. wyckii. The extensive variation in the number and chromosomal position of rDNA clusters observed among these Bagridae species may be related to the intense evolutionary dynamics of rDNA-repeated units, which generates divergent chromosomal distribution patterns even among closely related species. In summary, the distribution of repetitive DNA sequences provided novel, useful information regarding the evolutionary relationships between Bagridae fishes.


Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK-Positive Lung Cancer.
Purpose Advanced anaplastic lymphoma kinase ( ALK) fusion-positive non-small-cell lung cancers (NSCLCs) are effectively treated with ALK tyrosine kinase inhibitors (TKIs). However, clinical outcomes in these patients vary, and the benefit of TKIs is limited as a result of acquired resistance. Emerging data suggest that the ALK fusion variant may affect clinical outcome, but the molecular basis for this association is unknown. Patients and Methods We identified 129 patients with ALK-positive NSCLC with known ALK variants. ALK resistance mutations and clinical outcomes on ALK TKIs were retrospectively evaluated according to ALK variant. A Foundation Medicine data set of 577 patients with ALK-positive NSCLC was also examined. Results The most frequent ALK variants were EML4-ALK variant 1 in 55 patients (43%) and variant 3 in 51 patients (40%). We analyzed 77 tumor biopsy specimens from patients with variants 1 and 3 who had progressed on an ALK TKI. ALK resistance mutations were significantly more common in variant 3 than in variant 1 (57% v 30%; P = .023). In particular, ALK G1202R was more common in variant 3 than in variant 1 (32% v 0%; P < .001). Analysis of the Foundation Medicine database revealed similar associations of variant 3 with ALK resistance mutation and with G1202R ( P = .010 and .015, respectively). Among patients treated with the third-generation ALK TKI lorlatinib, variant 3 was associated with a significantly longer progression-free survival than variant 1 (hazard ratio, 0.31; 95% CI, 0.12 to 0.79; P = .011). Conclusion Specific ALK variants may be associated with the development of ALK resistance mutations, particularly G1202R, and provide a molecular link between variant and clinical outcome. ALK variant thus represents a potentially important factor in the selection of next-generation ALK inhibitors.


Mental health-related limitations and political leadership in Germany: A multidisciplinary analysis of legal, psychiatric, and ethical frameworks.
In recent years, political events have reignited contentious debates about psychiatry and democratic governance. This discourse has largely centred around the ethics and morality of public commentary, particularly in relation to the American Psychiatric Association's Goldwater Rule. Yet, few studies have examined the practical implications of health-related limitations due to mental illness in national leadership and the constitutional and legal provisions that surround these issues, including voluntary or involuntary proceedings. Accordingly, this theoretical paper analyses these topics in a German context using the position at the head of the executive: the chancellorship. Germany was selected as a case example as the biggest democracy in Europe with modern legal frameworks representative of the post-World War Two era in European constitutionalism, and for its economic and political influence within the European Union. Throughout this paper, we do not speculate on the mental health of any individual (past or present), but instead explore jurisdictional mechanisms around health-related limitations in German high office. Consequently, we outline relevant constitutional and legal scenarios, and how short- or long-term medical incapacity may determine requisite responses and contingent complexities. This underpins our discussion, where we consider legal ambiguities, functional capacity, and ethical concerns in psychiatric practice.


The ovine corticotropin-releasing hormone stimulation test in the differential diagnosis of adrenocorticotropic hormone-dependent cushing's syndrome.
To determine the efficacy of the ovine corticotropin-releasing hormone (oCRH) stimulation test in distinguishing between adrenocorticotropic hormone (ACTH)-dependent types of Cushing's syndrome. The cortisol and ACTH responses to intravenously administered oCRH were determined in 64 patients with pituitary-dependent Cushing's syndrome and 13 patients with ectopic ACTH production. Of the 64 patients with pituitary-dependent Cushing's syndrome, 57 (89%) had a positive ACTH response to administration of oCRH (an increase of 50% or more above baseline), and 56 (88%) had a positive cortisol response (an increase of 20% or more above baseline). One patient with an ectopic ACTH-secreting tumor had a false-positive cortisol response to administration of oCRH. Two patients with ectopic ACTH-secreting tumors had false-positive responses to both ACTH and cortisol after oCRH was administered. Because both these patients did not have hypercortisolemia at the time of testing, they were excluded from the statistical analysis. When analyzed on the basis of ACTH response alone, oCRH testing yielded a diagnostic sensitivity and specificity for the diagnosis of pituitary-dependent hypercortisolism of 89% and 100%, respectively. The positive predictive value was 100%, and the negative predictive value was 61%. oCRH testing distinguished between the ectopic ACTH syndrome and pituitary-dependent hyper-cortisolism in most cases. Therefore, this test is a useful procedure in the diagnostic evaluation of ACTH-dependent forms of Cushing's syndrome.


Modification of Cellulosic Materials with Boron-Nitrogen Compounds.
Wood fiber and its products are modified to increase fire and bio-resistance. The best results are achieved by using modifiers that enter into chemical interaction with the hydroxylated substrate, forming the organic matrix of the materials. The purpose of the research described in the article was to study the possibility of using boron-nitrogen compounds to modify cellulose and cellulose-containing materials to improve the performance, bio- and fire-protective properties of construction materials, as well as to optimize the consumption of boron-nitrogen compounds. As a result of the research, it was found that the boron-nitrogen compounds used in the compositions developed here chemically interact with hydroxyl groups at the C6-atom of cellulose. The chemical interaction of boron-nitrogen compounds with cellulose is an inter-crystalline process occurring without destruction of the crystal structure of the substrate since the modifier molecules bind with the more accessible hydroxyl groups of the amorphous regions of cellulose. Thus, surface modification with boron-nitrogen compounds does not result in accelerated aging of cellulose-containing materials and loss of strength but, on the contrary, increases the durability of wooden structures.


Seasat visible and infrared radiometer.
Visual and infrared images produced by the Seasat visible and infrared radiometer (VIRR) are adequate for the identification of cloud, land, and water features. A statistical comparison of VIRR-derived sea-surface temperatures in a cloud-free region with a National Oceanic and Atmospheric Administration analysis based on various surface measurements taken in the same region showed agreement to +/- 1.7 degrees K root-mean-square.


Modification of bacterial artificial chromosomes through chi-stimulated homologous recombination and its application in zebrafish transgenesis.
The modification of yeast artificial chromosomes through homologous recombination has become a useful genetic tool for studying gene function and enhancer/promoter activity. However, it is difficult to purify intact yeast artificial chromosome DNA at a concentration sufficient for many applications. Bacterial artificial chromosomes (BACs) are vectors that can accommodate large DNA fragments and can easily be purified as plasmid DNA. We report herein a simple procedure for modifying BACs through homologous recombination using a targeting construct containing properly situated Chi sites. To demonstrate a usage for this technique, we modified BAC clones containing the zebrafish GATA-2 genomic locus by replacing the first coding exon with the green fluorescent protein (GFP) reporter gene. Molecular analyses confirmed that the modification occurred without additional deletions or rearrangements of the BACs. Microinjection demonstrated that GATA-2 expression patterns can be recapitulated in living zebrafish embryos by using these GFP-modified GATA-2 BACs. Embryos microinjected with the modified BAC clones were less mosaic and had improved GFP expression in hematopoietic progenitor cells compared with smaller plasmid constructs. The precise modification of BACs through Chi-stimulated homologous recombination should be useful for studying gene function and regulation in cultured cells or organisms where gene transfer is applicable.


Dissecting cause and effect in host-microbiome interactions using the combined worm-bug model system.
High-throughput molecular studies are greatly advancing our knowledge of the human microbiome and its specific role in governing health and disease states. A myriad of ongoing studies aim at identifying links between microbial community disequilibria (dysbiosis) and human diseases. However, due to the inherent complexity and heterogeneity of the human microbiome we need robust experimental models that allow the systematic manipulation of variables to test the multitude of hypotheses arisen from large-scale 'meta-omic' projects. The nematode C. elegans combined with bacterial models offers an avenue to dissect cause and effect in host-microbiome interactions. This combined model allows the genetic manipulation of both host and microbial genetics and the use of a variety of tools, to identify pathways affecting host health. A number of recent high impact studies have used C. elegans to identify microbial pathways affecting ageing and longevity, demonstrating the power of the combined C. elegans-bacterial model. Here I will review the current state of the field, what we have learned from using C. elegans to study gut microbiome and host interactions, and the potential of using this model system in the future.


The economic burden of gastrointestinal stromal tumor (GIST) recurrence in patients who have received adjuvant imatinib therapy.
To estimate the economic burden of gastrointestinal stromal tumor (GIST) recurrence in patients who received imatinib adjuvant therapy. Data from the MarketScan and PharmMetrics databases between January 2000 and March 2013 were extracted. Patients who had received at least one diagnosis of GIST, had undergone a primary surgery for GIST, and had received at least one prescription for imatinib were included in the analysis. An algorithm was applied to identify those who had a subsequent GIST recurrence. Patients who experienced a recurrence and those who did not have a recurrence were compared for differences in healthcare utilization measures and healthcare costs within 6 months after the recurrence, while adjusting for potential confounding factors. A total of 540 patients with primary resectable GIST who received imatinib adjuvant therapy were identified, including 444 (82.2%) patients who did not experience GIST recurrence and 96 (17.8%) patients who did experience recurrence. Patients who experienced GIST recurrence utilized significantly more healthcare resources in all categories than patients who did not have a recurrence, including the number of hospitalizations, days of hospitalization, emergency room visits, outpatient visits, and other medical services (all p-values <0.01). The total healthcare cost was significantly higher for patients with GIST recurrence, with a difference of $4464 per patient per month (p < 0.01). Both the medical and pharmacy costs were significantly higher with adjusted differences of $3488 and $1423 per patient per month, respectively (both p-values <0.01). Patients who had GIST recurrence after surgical resection incurred significantly more healthcare resource utilization and greater healthcare costs within 6 months after the recurrence than patients who did not have recurrence. These findings suggest that GIST recurrence is associated with a substantial economic burden.


Implementation of an epilepsy self-management protocol.
It is essential that patients with epilepsy receive educational information about their disease and its management, but there is dissatisfaction with the education received. The purposes of this evidence-based project were to examine the current knowledge level and disease management behaviors of patients with epilepsy in an outpatient clinic and to measure the effectiveness of implementing a self-management protocol using the Epilepsy Self-Management Scale (ESMS). Pender's health promotion model and Rogers' diffusion of innovation theory were used to guide the development and completion of this project. An evidence-based epilepsy self-management protocol was developed and implemented at an outpatient neurology clinic by an interprofessional clinic team that consisted of (a) evaluation of self-management behaviors (ESMS), (b) individual education using the ESMS and developed resources, (c) follow-up telephone call, and (d) measurement of outcomes of the self-management protocol (patient self-management [ESMS] and process). Twenty patients participated in all or portions of the protocol. Scores on the ESMS increased from preimplementation to postimplementation of the protocol (t = -2.67). Seizure management and information management were identified as the most difficult self-management areas. Recommended changes in protocol implementation include adding information about safety measures such as medical alert bracelets and driving to the educational packets. Follow-up telephone calls were discontinued because of difficulties reaching patients. The results of this study suggest that the ESMS is an acceptable tool for evaluating patients' self-management behaviors. Epilepsy self-management protocols need to include both verbal and written educational materials. Educating patients with epilepsy about positive self-management behaviors may lead to better health outcomes.


Suicide attempts among activated soldiers in the U.S. Army reserve components.
Although the majority of active duty U.S. Army soldiers are full-time personnel in the Active Component (AC), a substantial minority of soldiers on active duty are in the Reserve Components (RCs). These "citizen-soldiers" (Army National Guard and Army Reserve) represent a force available for rapid activation in times of national need. RC soldiers experience many of the same stressors as AC soldiers as well as stressors that are unique to their intermittent service. Despite the important role of RC soldiers, the vast majority of military mental health research focuses on AC soldiers. One important goal of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is to address this gap. Here we examine predictors of suicide attempts among activated RC soldiers. This longitudinal, retrospective cohort study used individual-level person-month records from Army and Department of Defense administrative data systems to examine socio-demographic, service-related, and mental health predictors of medically documented suicide attempts among activated RC soldiers during 2004-2009. Data from all 1103 activated RC suicide attempters and an equal-probability sample of 69,867 control person-months were analyzed using a discrete-time survival framework. Enlisted soldiers comprised 84.3% of activated RC soldiers and accounted for 95.7% of all activated RC suicide attempts (overall rate = 108/100,000 person-years, more than four times the rate among officers). Multivariable predictors of enlisted RC suicide attempts included being female, entering Army service at age ≥ 25, current age < 30, non-Hispanic white, less than high school education, currently married, having 1-2 years of service, being previously deployed (vs. currently deployed), and history of mental health diagnosis (particularly when documented in the previous month). Predictors among RC officers (overall rate = 26/100,000 person-years) included being female and receiving a mental health diagnosis in the previous month. Discrete-time hazard models showed suicide attempt risk among enlisted soldiers was inversely associated with time in service. Risk factors for suicide attempt in the RCs were similar to those previously observed in the AC, highlighting the importance of research and prevention focused on RC enlisted soldiers in the early phases of Army service and those with a recent mental health diagnosis.


Evaluation of care given to patients suffering from erectile dysfunction by French urologists in 2018.
Erectile dysfunction varied by country, affecting between 20 to 40% of men aged 60 and 69 and more than 50% of men aged over 75. Our objective was to evaluate the habits of urologists in 2018 and also evaluate the need for additional, objective tools to aid physicians when providing care. A questionnaire was sent from the French Urology Association to 1158 physicians between November and December 2018. In all, 177 urologists (15.28%) took part in the study. Only 22% of urologists regularly used a questionnaire, such as the IIEF-5. When faced with erection problems, 56.5% of them did not carry out systematic cardiology evaluations. More than half of urologists requested fasting glucose, lipid and total testosterone levels. Twenty-seven percent did not carry out additional tests. First line treatment included a phosphodiesterase 5 inhibitor in 81% of cases. Two thirds of urologists (78%) rated themselves as being correctly trained in the area of erectile dysfunction. However, only 49% systematically inquired about erection problems when faced with benign prostatic hyperplasia and 65% thought that erectile dysfunction was not treated optimally. Despite existing recommendations, only half of urologists carry out a cardiac evaluation when a finding of erectile dysfunction is made. One third of urologists do not request additional testing. Greater training, along with the use of an objective diagnostic tool could help urologists to optimise the care they provide for patients suffering from erectile dysfunction, allowing them to keep working within current guidelines. LEVEL OF EVIDENCE: 3.


[Osler-Weber-Rendu disease. A case report].
Osler-Weber-Rendu disease, also known as hereditary hemorrhagic telangiectasia is an arteriovenous malformation of different organs and systems, due to fibrovascular displasia. The knowledge of its molecular genetic basis has developed in the last few years. Generally, these patients are evaluated each time they have hemorrhagic manifestations as isolated events, rather than integrating these events into a single disorder. This is the case of a patient who had several skin and visceral manifestations years before the diagnosis was made.


Cyclic AMP levels of C6 glioma cells treated with cis-dichlorodiammine platinum (cis-DDP).
Rat C6 glioma cells were cultured for 3-4 days in MEM supplemented with bovine serum. After 10 min incubation of cells with 0.075, 1.0 or 7.5 micrograms ml-1 cis-DDP the basal cAMP levels (7.87 +/- 0.4 pmoles mg-1 protein) were not affected. In the presence of a phosphodiesterase inhibitor, IBMX, an increase of cAMP occurred; the later was more pronounced in cis-DDP treated cells than in the controls. This suggests that both adenylate cyclase and cAMP-phosphodiesterase were proportionally influenced at this period and that the stimulatory effect of cis-DDP on AC could be demonstrated only when increased activity of PDE had been blocked by IBMX. At later time intervals (10 h-40 h), a 5- to 17-fold elevation of cAMP levels was observed even in the absence of IBMX. Pretreatment of the cells with cis-DDP significantly potentiated cAMP accumulation in response to NE alone and to cis-DDP plus NE could be prevented to a large extent by propranolol; in cis-DDP treated cells the propranolol protection was more effective, both in the absence and the presence of IBMX. The pretreatment of cells with an alpha-blocker, Regitin, did not significantly influence cAMP accumulation. The results indicate that the cis-DDP stimulated cAMP response to NE is mediated via an interaction with beta-adrenergic receptors. The late increase in cAMP content may be a mediator of the morphological changes in these cells following exposure to cis-DDP.


Return to pivoting sport after ACL reconstruction: association with osteoarthritis and knee function at the 15-year follow-up.
To examine the associations between return to pivoting sport following ACL reconstruction (ACLR) and knee osteoarthritis (OA), and self-reported knee symptoms, function and quality of life after 15 years. Study sample included 258 participants with ACLR 15 years previously. Return to pivoting sport (handball, soccer and basketball) data were collected by interviews, and symptomatic OA was defined as Kellgren and Lawrence grade ≥2 plus almost daily knee pain in the last month. Self-reported symptoms, function and quality of life were assessed with the Knee Injury and Osteoarthritis Outcome Score. Adjusted regression models were used to analyse the associations between return to pivoting sport and OA (present or not), and self-reported outcomes. P values ≤0.05 were considered statistically significant. Two hundred and ten (81%) participants (57% men) with a mean age of 39.1 (±8.7) years completed the 15-year follow-up, and 109 (52%) had returned to pivoting sport. Returning to pivoting sport was associated with less symptomatic OA (OR 0.28, 95% CI 0.09 to 0.89) and radiographic OA (OR 0.40, 95% CI 0.17 to 0.98), adjusted for age, sex, combined injury, self-reported knee function, and time between injury and surgery. Those who returned to pivoting sport had better function in activities of daily living (ADL). The participants with ACLR who returned to pivoting sport had lower odds of knee OA and better self-reported ADL function. Further investigation is required to understand the clinical significance of these findings.


Release dynamics of As, Co, and Mo in a biochar treated soil under pre-definite redox conditions.
This study assessed the impact of pre-definite redox potential (EH) on the release dynamics and distribution of As, Co, and Mo between the dissolved and colloidal phases as well as their potential mobility and phytoavailability in the sediment phase of a mining soil treated with rice hull biochar (BC). The experiment was conducted from controlled moderately-reducing to oxidizing conditions using an automated biogeochemical microcosm system. Arsenic and Mo were more abundant in the dissolved phase due to their predominant in potential mobile fractions, while Co was more abundant in the colloidal phase due to its association with Fe-(hydr)oxides. Biochar increased the dissolved and colloidal concentrations of As, the dissolved concentration of Co, and the colloidal concentration of Mo under oxidizing condition. On the other hand, the application of BC decreased the dissolved concentration of Mo and the colloidal concentration of Co in the first redox cycle under reducing-acidic condition, due to lower pH values, and chemistry of sulfide-sulfate and Fe/Mn oxides. The phytoavailability of As and Co were higher than their potential mobility in the sediment phase, while the same trend was not discerned for Mo. The potential mobility and phytoavailability of As and Co were high under oxic-acidic conditions. The potential mobility and phytoavailability of Mo might be increased under oxic condition due to the dissolution of Fe and Mn oxides under lower pH conditions, especially in the BC treated soil. Application of such rice hull BC to soil might stimulate the release of As, Co, and Mo under flooding conditions, which might increase the environmental and health risks in such wetland ecosystems.


Health economic evaluation in orthotics and prosthetics: a systematic review protocol.
Health economic evaluations are essential to support health care policy and investment decisions. To date, health economic evaluations in orthotics and prosthetics have focused on discrete components of an orthosis/prosthesis (e.g. a microprocessor controlled prosthetic knee joint) rather than the broader service provided by orthotist/prosthetists. As such, the contribution to orthotic/prosthetic policy and investment decisions is unclear. Whilst there are opportunities to conduct more informative health economic evaluations that describe the costs and benefits of the orthotic/prosthetic service, it is important that prospective research is informed by a critical review of the method design challenges and an understanding of how this research can be improved. The aim of this systematic review is to critically appraise the existing orthotic/prosthetic health economic evaluation literature and therefore determine evidence gaps, critical method design issues and the extent to which the literature informs orthotic/prosthetic policy and investment decisions. A comprehensive range of databases-AMED, EMBASE, MEDLINE and PsychINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), ProQuest Nursing and Allied Health, Web of Science, Cochrane Database of Systematic Reviews (CDSR) and specialty health economic databases-will be searched using National Library of Medicine Medical Subject Headings (MeSH) terms as well as the title, abstract, and keyword terms. Search terms related to the intervention (e.g. orthosis), including variants used by varying professional disciplines (e.g. brace), will be used in preference to defining the populations that use orthotic and prosthetic services (e.g. people living with rheumatoid arthritis). Search terms related to health economic evaluations will be guided by previously developed and tested search strings and align with recommendations by the Canadian Agency for Drugs and Technologies in Health. Articles meeting the inclusion criteria will be hand-searched for relevant citations, and a forward citation search using Google Scholar will also be conducted to identify early online articles not yet indexed in traditional databases. Original research published in the English language and after 1 January 2000 will be included. The Checklist for Health Economic Evaluation Reporting Standards (CHEERS) and the Consensus on Health Economic Criteria (CHEC)-Extended list will be used to appraise the methodological quality and identify sources of bias. Data extraction and appraisal will be conducted by one reviewer independently using appraisal instrument guidelines and a content specific decision aid with exemplars. A subsequent review by a second researcher will be undertaken to confirm the accuracy of the extraction and appraisal, and a final review by a third where consensus cannot be reached. The data will be extracted to a purpose-built data extraction template with decision-making guidelines to support consistency. Where possible, the findings of the review will be reported as a meta-analysis, although the heterogeneity of the literature will likely mean a narrative review that illuminates method design issues that contribute to imprecision and variation will be more appropriate. This protocol has been purposefully designed to summarise the existing evidence and appraise the methodological approaches used and the quality of the health economic evaluations in orthotics and prosthetics. What we learn from this review will be used to guide further work in this area and design more rigorous health economic evaluations into the future. PROSPERO CRD42018116910.


[Mechanism of IL-17 in colorectal inflammation-cancer transition].
Colitis associated colorectal cancer is a common intestinal malignant tumor, secondary to chronic enteritis. The persist existence of various inflammatory cells and cytokines in chronic inflammation promotes the development process of colitis-cancer transition. Interleukin 17 (IL-17) family, produced by Th17 cells, is found to be very important proinflammatory cytokines in various immune responses. In the proinflammatory response, IL-17 plays an important role in the activation and recruitment of neutrophils. Studies have shown the increased expression of IL-17 in serum and tumor tissues of patients with colorectal cancer. Th17 cells can induce the generation of immunosuppressive mediators including TGF-β, CXCR3, CCR6 and IL-6, which promotes the incidence of colorectal cancer. We summarized the role of IL-17 in the occurrence and progression of chronic colorectal inflammation to colorectal cancer, and elaborated the mechanisms by which IL-17 influences the formation of tumor microenvironment, promotes the proliferation, invasion and metastasis of tumor cells, and escapes immune surveillance.


Variable-number tandem repeat analysis of meningococcal isolates belonging to the sequence type 162 complex.
Thirty-one meningococcal isolates from carriers and disease cases belonging to the sequence type (ST) 162 complex, isolated in Greece in 1999 and 2000, were studied by the use of variable-number tandem repeat analysis. Our study demonstrated that the isolates belonging to the ST-162 clonal complex were a heterogeneous group. Based on this heterogeneity, it is unlikely that the disease-associated isolates represent an outbreak.


Safety and efficacy of misoprostol for induction of labour in a semi-urban hospital setting.
Most studies on the use of misoprostol for induction of labour have been carried out in well-endowed hospitals in developed countries with state-of-the-art monitoring equipment. There is need for more studies to be conducted in facilities with limited resources, if more patients are to benefit from the low cost and effectiveness of the drug. Following Ethical Committee approval, 152 women had labour induced in our maternity unit using intravaginal misoprostol. The patients were monitored clinically using the WHO model partograph with digital palpation of uterine contractions and intermittent auscultation of fetal heart with a pinard stethoscope. One hundred and thirty-five (88.8%) of the women had a vaginal delivery, while nine (5.9%) had a caesarean section for various obstetric indications. Eight cases of uterine hyperstimulation were noted but none of uterine rupture. We conclude that misoprostol can be used safely for induction of labour in less endowed hospital settings such as in developing countries, using basic clinical tools for monitoring.


[Bone mineral density in postmenopausal women with proximal femoral fractures--comparative study between quantitative ultrasonometry and gold standard DXA].
Osteoporosis associated proximal femoral fracture is a major public health problem. Diagnostic assessment includes patients history, laboratory testings and bone mineral density measurements. Hereby, dual X-ray absorptiometry (DXA) is regarded as the "Goldstandard". Quantitative ultrasonometry (QUS) of bone is a safe, simple, free of radiation, portable, cost-effective and therefore powerful diagnostic tool. QUS should be taken in account for primary assessment in patients with supposed osteoporosis in clinical practice. We performed this cross sectional pilot study to evaluate the ability of two different QUS-devices (os calcis) in comparison to DXA (lumbar spine and femoral neck) to discriminate postmenopausal women with proximal femoral fractures from healthy, age- and BMI-matched controls. All together, 44 postmenopausal women were included. Of these, 22 suffered a proximal femoral fracture and were compared with 22 healthy, age- and BMI-matched controls. Bone assessments were performed by DXA (femoral neck and lumbar spine) and QUS of the heel using Achilles and Insight. T- and Z-Score of DXA (femoral neck) were significantly lower in women with hip fracture compared to controls (p < 0.008 and p < 0.01). QUS-Insight also revealed significantly lower values of T- and Z-Score in women with hip fracture compared to controls (p < 0.01 and p < 0.005). QUS-Achilles measurement results also comprised significant differences between the groups (T-Score und Z-Score: p < 0.02). In accordance to the T-Score (femoral neck), all three devices (DXA femoral neck, Achilles and Insight) showed an equal significant correlation (p < 0.001). The correlation in between both QUS-devices was higher (0.956; p < 0.0001) than in between DXA-results (femoral neck vs. lumbar spine, 0.577; p < 0.01). The Z-Score also showed a significant correlation. DXA (lumbar spine) didn't show any significant differences in T- and Z-Score. In comparison to the gold standard DXA (femoral neck), both QUS-devices showed an equal ability to significantly discriminate postmenopausal women with proximal femoral fractures from healthy, age- and BMI-matched controls. If our results are confirmed by more cross-sectional and longitudinal studies, QUS could be a helpful and valuable technique in clinical practice. Finally, all patients with osteoporosis-related fractures should be thoroughly investigated during their hospitalisation and effective treatment must be instituted.


Type 2 cytokines sensitize human sensory neurons to itch-associated stimuli.
Chronic itch is a central symptom of atopic dermatitis. Cutaneous afferent neurons express receptors interleukins (IL)-4, IL-13, and IL-33, which are type 2 cytokines that are elevated in atopic dermatitis. These neuronal cytokine receptors were found to be required in several murine models of itch. Prior exposure of neurons to either IL-4 or IL-33 increased their response to subsequent chemical pruritogens in mice but has not been previously examined in humans. The objective of the present study was to determine if type 2 cytokine stimulation sensitizes sensory neurons to future itch stimuli in a fully human ex vivo system. We measured calcium flux from human dorsal root ganglia cultures from cadaveric donors in response to pruritogens following transient exposure to type 2 cytokines. We also measured their effect on neuronal calcium flux and changes in gene expression by RNA sequencing. Type 2 cytokines (IL-4, IL-13, and IL-33) were capable of sensitizing human dorsal root ganglia neurons to both histaminergic and nonhistaminergic itch stimuli. Sensitization was observed after only 2 h of pruritogen incubation. We observed rapid neuronal calcium flux in a small subset of neurons directly in response to IL-4 and to IL-13, which was dependent on the presence of extracellular calcium. IL-4 and IL-13 induced a common signature of upregulated genes after 24 h of exposure that was unique from IL-33 and non-type 2 inflammatory stimuli. This study provides evidence of peripheral neuron sensitization by type 2 cytokines as well as broad transcriptomic effects in human sensory ganglia. These studies identify both unique and overlapping roles of these cytokines in sensory neurons.


GC-MS olfactometric and LC-DAD-ESI-MS/MS characterization of key odorants and phenolic compounds in black dry-salted olives.
Olives are processed in different ways depending on consumption habits, which vary between countries. Different de-bittering methods affect the aroma and aroma-active compounds of table olives. This study focused on analyzing the aroma and aroma-active compounds of black dry-salted olives using gas chromatography-mass spectrometry-olfactometry (GC-MS-O) techniques. Thirty-nine volatile compounds which they have a total concentration of 29 459 µg kg-1 , were determined. Aroma extract dilution analysis (AEDA) was used to determine key aroma compounds of table olives. Based on the flavor dilution (FD) factor, the most powerful aroma-active compounds in the sample were methyl-2-methyl butyrate (tropical, sweet; FD: 512) and (Z)-3-hexenol (green, flowery; FD: 256). Phenolic compounds in table olives were also analyzed by LC-DAD-ESI-MS/MS. A total of 20 main phenolic compounds were identified and the highest content of phenolic compound was luteolin-7-glucoside (306 mg kg-1 ), followed by verbascoside (271 mg kg-1 ), oleuropein (231 mg kg-1 ), and hydroxytyrosol (3,4-DHPEA) (221 mg kg-1 ). Alcohols, carboxylic acids, and lactones were qualitatively and quantitatively the dominant volatiles in black dry-salted olives. Results indicated that esters and alcohols were the major aroma-active compounds. © 2018 Society of Chemical Industry.


A new statistical method for estimating the usual intake of episodically consumed foods with application to their distribution.
We propose a new statistical method that uses information from two 24-hour recalls to estimate usual intake of episodically consumed foods. The method developed at the National Cancer Institute (NCI) accommodates the large number of nonconsumption days that occur with foods by separating the probability of consumption from the consumption-day amount, using a two-part model. Covariates, such as sex, age, race, or information from a food frequency questionnaire, may supplement the information from two or more 24-hour recalls using correlated mixed model regression. The model allows for correlation between the probability of consuming a food on a single day and the consumption-day amount. Percentiles of the distribution of usual intake are computed from the estimated model parameters. The Eating at America's Table Study data are used to illustrate the method to estimate the distribution of usual intake for whole grains and dark-green vegetables for men and women and the distribution of usual intakes of whole grains by educational level among men. A simulation study indicates that the NCI method leads to substantial improvement over existing methods for estimating the distribution of usual intake of foods. The NCI method provides distinct advantages over previously proposed methods by accounting for the correlation between probability of consumption and amount consumed and by incorporating covariate information. Researchers interested in estimating the distribution of usual intakes of foods for a population or subpopulation are advised to work with a statistician and incorporate the NCI method in analyses.


Laboratory behavioural assay of insect magnetoreception: magnetosensitivity of Periplaneta americana.
A relatively simple all-laboratory behavioural assay of insect magnetoreception has been developed. We found non-conditioned reactions of American cockroach to the periodical shifts of the geomagnetic field. The movement activity of animals individually placed into Petri dishes was scored as a number of body turns. Test groups were exposed to a 90-min interval with the horizontal component of the geomagnetic field periodically rotated by 60 degrees back and forth with 5 min periodicity. The number of body turns was compared with the preceding and following intervals and with the corresponding interval of the control group kept in the natural field. We obtained a significant increase in activity when changes in field were applied. Interestingly, the period of increased activity did not coincide precisely with the 90 min stimulation interval. The onset of animal restlessness was delayed by tens of minutes and persisted correspondingly after the stimulation stopped. A respective evaluation criterion was suggested and verified. Owing to its simplicity and minimal manipulation of the insects, together with low demands on the memory and motivation state of animals, the approach potentially may be used as a laboratory diagnostic tool indicating magnetoreception in insect neurophysiology research.


Caregivers' Perceptions of a High Repetition Sit-To-Stand Exercise Program for Children with Cerebral Palsy Who Have Mobility Limitations.
To explore caregiver perceptions about the outcomes and feasibility of a high repetition sit-to-stand home-based exercise program on themselves and their children with cerebral palsy who have mobility limitations. Face-to-face semi-structured interviews were conducted with 19 caregivers (17 women, mean age 39 y 6 mo (SD 8 y 4 mo) of 19 children with cerebral palsy (10 males, mean age 7 y 2 mo (SD 2 y 1 mo) classified as level III (n = 8) or IV (n = 11) on the Gross Motor Function Classification System. The children had completed a 6-week task-specific sit-to-stand exercise program. Each week a physical therapist and caregivers supervised the program: twice by the physical therapist and three times by the caregivers. Interviews were completed immediately after program completion, and transcripts were analyzed using a process of inductive thematic analysis within an interpretive description framework. Themes were: (1) caregivers saw positive changes in their children from completing the program, (2) seeing positive changes gave caregivers hope that their child could develop with further training, and (3) the program was feasible to complete. Caregivers perceived positive changes in their children and expressed increased hope for their child's future after a high repetition sit-to-stand exercise program, suggesting the program is feasible with caregiver supervision.


Exercise level and cognitive decline: the MoVIES project.
Growing evidence suggests that physical exercise may be protective against cognitive impairment and decline. A prospective study of a representative rural community sample (N = 1,146) aged 65+ years examined self-reported exercise habits and measured global cognitive function using the Mini-Mental State Examination (MMSE). A composite variable "exercise level" combining type, frequency, and duration of exercise was created with three levels: "high exercise" (aerobic exercise of > or = 30 minute duration > or = 3 times a week), "low exercise" (all other exercise groups), and "no exercise." Cognitive decline was defined as being in the 90 percentile of decline in this cohort, ie, declining by 3 or more MMSE points during the 2-year interval between two assessments. In a multiple regression model, high exercise level at the baseline assessment was negatively associated with, ie, was protective against, being in the group with the greatest amount of decline at the follow-up assessment, after adjusting for likely confounders (odds ratio = 0.39; 95% confidence interval, 0.19, 0.78). When high exercise was redefined using frequency as > or = 5 days per week as the threshold, as per the Surgeon General's guidelines, both low exercise and high exercise were negatively associated with cognitive decline. Exercise may have implications for prevention of cognitive decline.


Beyond Progression: Devising a New Training Model for Candidate Assessment, Advancement, and Advising at Columbia.
Research over several decades has identified significant problems with the progression model-the traditional approach to assessment and advancement of psychoanalytic candidates-including candidates' anxiety and uncertainty about the methods and fairness of their assessment, avoidance of conflictual issues with patients in order to keep cases, and reluctance to share their challenges with supervisors and advisors. In light of these findings, the Columbia Center for Psychoanalytic Training and Research restructured its psychoanalytic training programs. The progression committee, the progression advisor role, candidate application to advance through the program, and routine committee discussion of candidates were eliminated and replaced by confidential mentorship and a clear and predictable system of trainee advancement. Analytic competency-a requirement for graduation-is now determined solely from detailed written feedback regarding the candidate's achievement of the Center's learning objectives. The number of months of supervised analysis required for graduation has been reduced, as has the required length of the candidate's longest case; in addition, three-times-weekly analyses are now accepted for credit. These changes are meant to increase the transparency, objectivity, and predictability of the training experience and reduce the pressure on clinical decision making and communication between trainees and faculty. An extensive evaluation of the impact of these innovations is currently under way.


En Route to 2-(Cyclobuten-1-yl)-3-(trifluoromethyl)-1H-indole.
A six-step synthetic route from 4-chloro-2-methylaniline to 5-chloro-2-(cyclobut-1-en-1-yl)-3-(trifluoromethyl)-1H-indole (1) has been reported. Compound 1a is a key impurity of reverse transcriptase inhibitor efavirenz, an important anti-HIV/AIDS drug. Synthetic challenges, dead ends, and detours are discussed.


[Preventative biology of type 1 diabetes: implications for clinical preventative studies].
Type 1 diabetes is a multifactorial disease caused by an interplay of poorly known environmental factors and partially characterized genetic factors. Focal infiltration of the endocrine pancreas by mononuclear cells and a strikingly decreased functional beta cell mass constitute the histopathological hallmarks of the disease at diagnosis, but there is a marked interindividual variability in terms of the extent of the lesions. The disease process is triggered long before clinical onset as testified by the appearance of circulating islet cell autoantibodies years before the development of hyperglycemia. After diagnosis the current insulin substitution therapy is unable to completely avoid the occurrence of the chronic complications of hyperglycemia. The design of effective prevention of hyperglycemia in subjects at risk or of a lasting cure in patients intends to eradicate the development of the invalidating chronic complications. Such clinical studies are complicated by the existence of large interindividual differences in the progression of beta cell destruction, both before and after diagnosis. Therefore it is important to first biologically characterize larger representative groups of patients and subjects at increased risk (e.g. first degree relatives), and to follow them up clinically in order to establish objective criteria for the selection of study subjects with a more homogeneous risk of beta cell destruction for participation in clinical prevention studies. In Belgium a national collaborative program--the Belgian Diabetes Registry--has allowed to collect epidemiological, clinical and biological data in more than 3,500 patients and more than 6,000 relatives. The detection of islet cell-specific autoantibodies--if possible complemented with genetic and hormonal markers--facilitates the identification of subjects at high risk of rapid beta cell destruction. For example, in first degree relatives the combined presence of IA-2 antibodies and the HLA-DQ2/DQ8 genotype defines a small group of subjects (< 1%) with 75% risk of diabetes within 5 years. They qualify for participation in intervention studies aiming at beta cell mass preservation. These findings have helped to prepare several prevention studies in Belgium.


Comparative effectiveness of coronary artery stenosis and atherosclerotic plaque burden assessment for predicting 30-day revascularization and 2-year major adverse cardiac events.
To provide comparative prognostic information of coronary atherosclerotic plaque volume and stenosis assessment in patients with suspected coronary artery disease (CAD). We followed 372 patients with suspected or known CAD enrolled in the CORE320 study for 2 years after baseline 320-detector row cardiac CT scanning and invasive quantitative coronary angiography (QCA). CT images were analyzed for coronary calcium scanning (CACS), semi-automatically derived total percent atheroma volume (PAV), segment stenosis score (SSS), in addition to traditional stenosis assessment (≥ 50%) by CT and QCA for (1) 30-day revascularization and (2) major adverse cardiac events (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare accuracy of risk prediction. Sixty percent of patients had obstructive CAD by QCA with 23% undergoing 30-day revascularization and 9% experiencing MACE at 2 years. Most late events (20/32) were revascularization procedures. Prediction of 30-day revascularization was modest (AUC range 0.67-0.78) but improved after excluding patients with known CAD (AUC range 0.73-0.86, p < 0.05 for all). Similarly, prediction of MACE improved after excluding patients with known CAD (AUC range 0.58-0.73 vs. 0.63-0.77). CT metrics of atherosclerosis burden performed overall similarly but stenosis assessment was superior for predicting 30-day revascularization. Angiographic and coronary atherosclerotic plaque metrics perform only modestly well for predicting 30-day revascularization and 2-year MACE in high risk patients but improve after excluding patients with known CAD. Atherosclerotic plaque metrics did not yield incremental value over stenosis assessment for predicting events that predominantly consisted of revascularization procedures. NCT00934037.


Steered molecular dynamics simulations on the peeling and shearing of carbon nanotubes on a silicon substrate.
Steered molecular dynamics simulations were performed to investigate the peeling and shearing behavior of a single-walled carbon nanotube lying on a silicon substrate. Both the constant velocity and the constant force methods were applied to explore the adsorption of carbon nanotube and silicon substrate, and the efficiency of the two simulation methods was compared via a few representative examples. We examined the influences of the peeling angle, the shearing velocity, the initial distance between the carbon nanotube and the substrate, the connection point with the virtual ideal spring, the tube radius, as well as the 5-7-7-5 and radius defect of the carbon nanotube. The numerical results coincide well with relevant experimental results. This work is helpful for the application of carbon nanotubes in silicon-based microelectronics.


Application of statistical models to estimate the correlation between urinary benzene as biological indicator of exposure and air concentrations determined by personal monitoring.
This study evaluated the correlation between benzene in urine and in workplace air at low airborne benzene levels (below 1 ppm). Eleven workers were monitored over a period of 1-4 days at a petrochemical plant in Italy; samples of end-of-shift urine and workplace air were analyzed for benzene. A significant correlation, with a coefficient of determination R(2)=0.63, was found between urine and airborne benzene, confirming the results of previous studies. Two different statistical models were utilized to estimate urine benzene values of 9-16 microg/L corresponding to the American Conference of Governmental Industrial Hygienists' threshold limit value (TLV) of 0.5 ppm in workplace air. Not withstanding the variability inherent to biological monitoring, the results suggest application of biomonitoring as a trigger for identification of lower exposure level below, but approaching the TLV. Additionally, the proposed benzene biomonitoring may be useful in evaluating PPE effectiveness and use characteristics as well as dermal contribution to total exposure.


Understudied Anophelines Contribute to Malaria Transmission in a Low-Transmission Setting in the Choma District, Southern Province, Zambia.
Malaria transmission has declined substantially in Southern Province, Zambia, which is considered a low-transmission setting. The Zambian government introduced a reactive test-and-treat strategy to identify active zones of transmission and treat parasitemic residents. This study was conducted in the Choma District, Southern Province, Zambia, concurrently with an evaluation of this strategy to identify vectors responsible for sustaining transmission, and to identify entomological, spatial, and ecological risk factors associated with increased densities of mosquitoes. Anophelines were collected with CDC light traps indoors and near animal pens in index cases and neighboring households. Outdoor collections captured significantly more anophelines than indoor traps, and 10 different anopheline species were identified. Four species (Anopheles arabiensis, An. rufipes, An. squamosus, and An. coustani) were positive for Plasmodium falciparum circumsporozoite protein by ELISA, and 61% of these 26 anophelines were captured outdoors. Bloodmeal assays confirm plasticity in An. arabiensis foraging, feeding both on humans and animals, whereas An. rufipes, An. squamosus, and An. coustani were largely zoophilic and exophilic. Linear regression of count data for indoor traps revealed that households with at least one parasitemic resident by polymerase chain reaction testing was associated with higher female anopheline counts. This suggests that targeting households with parasitemic individuals for vector interventions may reduce indoor anopheline populations. However, many vectors species responsible for transmission may not be affected by indoor interventions because they are primarily exophilic and forage opportunistically. These data underscore the necessity for further evaluation of vector surveillance and control tools that are effective outdoors, in conjunction with current indoor-based interventions.


Presence and seasonal variation of trihalomethanes (THMs) levels in drinking tap water in Mostaganem Province in northwest Algeria.
The use of chlorine to disinfect water, produces various disinfection byproducts such as trihalomethanes (THMs). These compounds are formed when free available chlorine reacts with natural organic matter in raw water during water disinfection. Epidemiologic studies have shown an association between long-term exposure to THMs and an increased risk of cancer, all of them are suspected of having carcinogenic effects. The aim of this study was to determine the presence of THMs in the drinking tap water of Mostaganem Province (Algeria) in order to assess the seasonal variation in trihalomethane levels in tap water and to identify the season of high risk to the consumer. This analytical study was conducted in Mostaganem Province, Algeria in March, July, September and December 2015. Primarily, we proceeded to collect 30 samples from different areas of Mostaganem Province which were marked with a higher level of residual chlorine for the year 2015; secondly, we utilised the HS-SPME method for determination of trihalomethanes in drinking tap water over a period of four months. For comparison of trihalomethanes values, we used ANOVA. The results obtained show variability in total THM concentrations from one district to another, with a maximum of 198 μg/l recorded in the Achaacha district during July, but the lowest value 07.84 μg/l is noted at Salamandre city during the same period, noting that these values decrease progressively during the winter period. Our drinking tap water samples include a large quantity of THMs with different concentrations, where the dibromochloromethane and the bromoform constitute the major portion of THMs.


[Neurosyphilis mortality in a psychiatric hospital over a 50-year period].
Through information gathered at the statistical and medical register service it was done a descriptive study of some epidemiologic aspects of neurosyphilis at the Juliano Moreira Hospital (Bahia) in a period of 50 years (1930 - 1979). Coeficients of specific mortality were stablished . The distribution of the disease was analyzed according to sex, diagnosis in relation to the year, decades and periods before and after penicilinotherapy . Based on the results it is possible to conclude that: neurosyphilis has a cyclic character in epidemiologic level; women are more resistant or less exposed to the disease; males are more often affected; with the penicilinotherapy it was observed a progressive decrease of mortality; the last death caused by neurosyphilis at the Juliano Moreira Hospital occurred in 1971.


Stepped osteotomy of femoral head autograft for acetabular reconstruction in total hip arthroplasty for dysplasia of the hip: 3 to 12 years' results.
This study aims to describe a stepped osteotomy technique applied to the femoral head autograft to keep the graft volume at a sufficient level, provide primary stability, and direct cancellous-cancellous bone contact. In this retrospective study, 24 hips of 20 patients (5 males, 15 females; mean age 53 years; range, 43 to 68 years) with dysplasia of the hip (DDH) who underwent total hip arthroplasty with femoral head stepped osteotomy technique were evaluated between April 2003 and June 2010. Patients' age, gender, operation side, and postoperative complications were recorded. Aseptic loosening of the acetabular cup and graft integration/resorption were evaluated radiographically. Radiological evaluations were performed according to the methods of DeLee and Charnley, and Mulroy and Harris. Functional status of the patients was determined according to the criteria of Merle d'Aubigné and Postel, and Harris hip score (HHS). The mean follow-up period was 5.5 years (range, 3 to 12 years). None of the patients had any complications in the early postoperative period. In all patients, the percentage of acetabular component coverage by the graft was measured as 27% (range, 19 to 38%) on average. At the last follow-up, all patients were satisfied with the result and there was no sign of clinically loosening, osteointegration was complete, and there was no radiographic evidence of graft resorption or collapse of any hip. The overall Merle d'Aubigné scores and HHSs of the patients significantly improved at the final follow-up. This stepped osteotomy technique increases the probability of osteointegration, reduces the need for early revision, and provides reliable stability with satisfactory clinical and radiological midterm results.


Alzheimer's disease risk genes and the age-at-onset phenotype.
Despite the recent identification of several novel risk genes for Alzheimer's disease (AD), little is known about their influence on the age at onset (AAO) of AD. The AAO is a phenotype with a heritable component distinct from disease risk and may be a useful trait to study in the context of developing interventions for delaying the onset of AD. We studied the influence of 10 recently identified AD risk genes and APOE in relation to AAO in a large cohort of AD patients (N = 2569). We find that the novel AD risk gene, PICALM, exerts a small effect on the AAO of AD with earlier disease onset in risk allele carriers. In addition, we confirmed the previously reported association between the APOE ε4 allele and earlier disease onset. None of the other AD risk genes influenced AAO of AD. Our results suggest that besides APOE, other genes associated with AD risk do not exert large effects on the AAO phenotype of AD.


Cholesterol in Higher Plants.
The presence of cholesterol in Solanum tuberosum and Dioscorea spiculiflora plants was demonstrated by gas-liquid chromatography, thin-layer chromatography, isolation and mixed melting point, and purification to constant radioactivity after dilution with authentic cholesterol.


Treating female infertility and improving IVF pregnancy rates with a manual physical therapy technique.
Infertility and pregnancy. To assess the effectiveness of site-specific manual soft tissue therapy in (1) facilitating natural fertility and (2) improving in vitro fertilization (IVF) pregnancy rates in women with histories indicating abdominopelvic adhesion formation. Pursuant to 2 promising pilot studies, 53 infertile, premenopausal patients received a 10- to 20-hour series of site-specific manual physical therapy treatments. Seventeen patients hoped to achieve a natural pregnancy; 36 planned to undergo IVF within 15 months. The primary criteria for inclusion in the studies were the inability to conceive following a minimum of 12 months of unprotected intercourse and suspected or confirmed pelvic adhesions due to abdominal and/or pelvic surgery, infectious or inflammatory disease (eg, endometriosis, PID), or trauma. Treatments were specifically designed to address biomechanical dysfunctions of the pelvis, sacrum, and coccyx and restricted soft tissue and visceral mobility due to adhesions or microadhesions affecting the reproductive organs and adjacent structures. (1) Natural fertility group: pregnancy within 1 year of therapy and subsequent full-term delivery; (2) Pre-IVF group: pregnancy (via transfer of fresh embryos from nondonor eggs) within 15 months of the last manual treatment date. Natural fertility group: Of the 14 patients available for follow-up (ages 25 to 44; mean, 33.5 years), 10 (71.4%) became pregnant within 1 year, and 9 (64.3%) reported full-term deliveries. Three of the 9 women who delivered reported a subsequent pregnancy, suggesting that the treatment protocol might have lasting effects. Two women have had a second live birth delivery; and the third is still pregnant. Pre-IVF group: Of the 25 patients available for follow-up (ages 28 to 44; mean, 36 years), clinical pregnancies were documented in 22 of 33 embryo transfers vs the US Centers for Disease Control and Prevention (CDC) 2001 age-adjusted expected number of 12.7 (P < .001). The estimated odds ratio for a successful pregnancy in a cycle (manual treatment: no treatment) is 3.20 (95% confidence interval = 1.55-8.4). The data trend across these studies suggests that this innovative site-specific protocol of manual soft-tissue therapy facilitates fertility in women with a wide array of adhesion-related infertility and biomechanical reproductive organ dysfunction. The therapy, designed to improve function by restoring visceral, osseous, and soft-tissue mobility, is a nonsurgical, noninvasive manual technique with no risks and few, if any, adverse side effects or complications. As such, it should be considered a new adjunct to existing medical infertility treatments.


[Ultrastructure of the vestibular apparatus in patients with Meniere's disease].
The vestibular labyrinth of eight patients with Menière's disease obtained by translabyrinthine vestibular neurectomy or transtympanal labyrinthectomy was studied with the light microscope and transmission electron microscope. Previous invasive therapy was transtympanal application of gentamicin in one patient and endolymphatic sac surgery in two patients. Some of the pathological findings were unspecific, e.g. mucoid degeneration of the subepithelial spaces, fibrous long spacing collagen and high amount of lipofuscin in different cell types. Cuticular laminated structures were seen in some of the specimen. A most interesting finding was the discrepancy of large numbers of sub- and intraepithelial nerve fibers and a significant degeneration of vestibular sensory cells with vacuoles and filament bundles. This points out the importance of combining labyrinthectomy and vestibular neurectomy in late stages of unilateral Menière's disease.


Resonant coupling in trenched bend-insensitive optical fiber.
We report in this Letter the resonant coupling mechanism in bending trenched bend-insensitive fiber (BIF). It is found that among the trench parameters, the core-trench distance is predominant for optimized BIF design. We reveal that resonant coupling is an intrinsic characteristic of bending trenched BIF, and resonant coupling between the fiber core and the innermost cladding would limit the ultimate bending loss of BIF under tight bend. Resonant coupling is also present in double-trenched BIF, and would impair its bending performance.


Severity of childhood obstructive sleep apnea and hypertension improved after adenotonsillectomy.
To report improvements in childhood obstructive sleep apnea (OSA) and hypertension after adenotonsillectomy. Case series with planned data collection. Tertiary referral center. Fifty consecutive patients (36 boys and 14 girls; median age, 7.0 years) who underwent plasma knife-assisted total tonsillectomy and adenoidectomy for OSA between January 2010 and March 2013 were assessed with the body mass index z score, apnea-hypopnea index (AHI), systolic blood pressure (BP), and diastolic BP at baseline and at ≥6 months postoperatively. Changes in these parameters were statistically analyzed using nonparametric tests with the bootstrap approach. The median follow-up period was 9.6 months. Postoperatively, the median AHI significantly reduced from 9.8 to 1.6 (P<.001). Although the median systolic BP and diastolic BP insignificantly changed in the overall group, both were significantly reduced in children with preoperative hypertension (systolic: from 119.0 to 113.0 [P=.038]; diastolic: from 79.0 to 68.0 [P=.005]). Accordingly, the hypertension rate significantly reduced from 34% to 14% (P=.006). However, the change in OSA severity was not well correlated with the change in hypertension severity. In multiple logistic regression analysis with forward selection, a combination of preoperative hypertension and severe OSA was a significant predictor of postoperative hypertension (relative risk, 15.4; 95% confidence interval, 3.7-64.3; P<.001). The decreased hypertension rate indicates that a reduction of the AHI is not all that matters after adenotonsillectomy in childhood OSA. However, patients with preoperative severe OSA and hypertension need careful management of their elevated BP despite surgical treatment.


Hidden Gems in the Transcriptome Maps of Competent Streptococci.
Natural transformation is regarded as an important mechanism in bacteria that allows for adaptation to different environmental stressors by ensuring genome plasticity. Since the discovery of this phenomenon in Streptococcus pneumoniae, remarkable progress has been made in the understanding of the molecular mechanisms and pathways coordinating this process. Recently, the advent of high-throughput sequencing allows the posing of questions that address the system at a larger scale but also allow for the creation of high-resolution maps of transcription. Thus, while much is already known about genetic competence in streptococci, recent studies continue to reveal intricate novel regulation pathways and components. In this perspective article, we highlight the use of transcriptional profiling and mapping as a valuable resource in the identification and characterization of "hidden gems" pertinent to the natural transformation system. Such strategies have recently been employed in a variety of different species. In S. mutans, for example, genome editing combined with the power of promoter mapping and RNA-Seq allowed for the identification of a link between the ComCDE and the ComRS systems, a ComR positive feedback loop mediated by SigX, and the XrpA peptide, encoded within sigX, which inhibits competence. In S. pneumoniae, a novel member of the competence regulon termed BriC was found to be directly under control of ComE and to promote biofilm formation and nasopharyngeal colonization but not competence. Together these new technologies enable us to discover new links and to revisit old pathways in the compelling study of natural genetic transformation.


The use of brain functional magnetic resonance imaging to determine the mechanism of action of gabapentin in managing chronic pelvic pain in women: a pilot study.
To inform feasibility and design of a future randomised controlled trial (RCT) using brain functional MRI (fMRI) to determine the mechanism of action of gabapentin in managing chronic pelvic pain (CPP) in women. Mechanistic study embedded in pilot RCT. University Hospital. Twelve women (18-50 years) with CPP and no pelvic pathology (follow-up completed March 2014). Oral gabapentin (300-2700 mg) or matched placebo. After 12 weeks of treatment, participants underwent fMRI of the brain (Verio Siemens 3T MRI) during which noxious heat and punctate stimuli were delivered to the pelvis and arm. Outcome measures included pain (visual analogue scale), blood oxygen level dependent signal change and a semi-structured acceptability questionnaire at study completion prior to unblinding. Full datasets were obtained for 11 participants. Following noxious heat to the abdomen, the gabapentin group (GG) had lower pain scores (Mean: 3.8 [SD 2.2]) than the placebo group (PG) (Mean: 5.8 [SD 0.9]). This was also the case for noxious heat to the arm with the GG having lower pain scores (Mean: 2.6 [SD 2.5]) than the PG (Mean: 6.2 [SD 1.1]). Seven out of 12 participants completed the acceptability questionnaire. 71% (five out of seven) described their participation in the fMRI study as positive; the remaining two rated it as a negative experience. Incorporating brain fMRI in a future RCT to determine the mechanism of action of gabapentin in managing CPP in women was feasible and acceptable to most women. ISRCTN70960777.