Acute epididymitis induces alterations in sperm protein composition.
To use a proteomic approach to evaluate possible postinflammatory alterations in the protein composition of motile sperm in patients 3 months after acute epididymitis. Prospective case-control study. University medical school research laboratory. Eight patients 3 months after acute unilateral epididymitis and 10 healthy controls. None. Proteome analysis of sperm samples collected by swim-up from control and acute epididymitis patients analyzed by two-dimensional gel electrophoresis and subsequent protein identification by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry; immunofluorescence staining for mitochondrial ATP synthase subunit β (ATP5B), α-tubulin (TUBA1A), and tubulin-β2c (TUBB4B) for validation purposes. Proteome analysis identified 35 proteins in sperm from epididymitis patients that were down-regulated, irrespective of subcellular localization and biologic function. Furthermore, immunofluorescence microscopy confirmed ATP5B, TUBA1A, and TUBB4B were less abundantly expressed in epididymitis samples compared with controls. Despite normal semen parameters observed by conventional semen analysis in patients after epididymitis, significant changes to sperm protein composition were observed. These changes may be implicated as additional factors contributing to subfertility/infertility in men after episodes of epididymitis.


Median and ulnar nerves in the hand.
There are a multitude of different testing techniques to evaluate the median and ulnar nerves for abnormalities at the wrist and hand. The electrodiagnostician should be able to use his or her knowledge of anatomy, history, physical examination, and electrophysiology to accurately diagnose common median and ulnar nerve dysfunction in the distal upper extremity.


Effect of eugenol-based root canal sealers on retention of prefabricated metal posts luted with resin cement.
This study evaluated the effect of two different eugenol-based root canal sealers on the retention of prefabricated metal posts luted with adhesive resin cement. Thirty prefabricated ParaPosts randomly divided among three groups of 10 each were luted into extracted single-rooted teeth with adhesive resin cement. Two of the groups had been obturated with Gutta-Percha and one of two eugenol-based root canal sealers (Endofil and Tubli-Seal), respectively. The third group was not obturated and served as the control. The forces required for dislodgment of posts from their prepared post spaces were recorded using a universal testing machine. Data were statistically analyzed using one-way ANOVA and Tukey's multiple range test was used to determine the mean differences. Endofil and Tubli-Seal groups demonstrated significantly reduced retention compared to the unobturated (control) group (P < 0.05). Eugenol-based sealers significantly reduced the retention of prefabricated posts luted with adhesive resin cement.


Relationship between vitamin D status and deposition of bound calcium in skeletal muscle of the rat.
The effects of vitamin D on the intramuscular distribution of total and bound calcium, phosphate and on available cytosolic calcium, were investigated in skeletal muscle. Total calcium and phosphorus were measured on ashed subcellular fractions of muscles from vitamin D-repleted and vitamin D-deprived rats. The variations in available calcium were followed by determining the activities of calcium-sensitive enzymes in isolated cytosol. Bound-calcium was revealed ultra-microscopically by pyroantimonate. In vitamin D-repleted muscles, the pyroantimonate method revealed specific areas of intense bound-calcium deposition: the myofibrils, where they formed pronounced lines parallel to the Z-bands. In vitamin D-deficient muscles, the calcium-pyroantimonate deposits appeared clearly reduced. This loss was accompanied by a marked reduction in total calcium and phosphorus in all the subcellular fractions, as compared to vitamin D-repleted muscles. Unexpectedly, the activity of the Ca(+)-activated isocitrate-dehydrogenase was increased in the cytosol, while that of the Ca2(+)-inhibited pyruvate-kinase decreased. Prolonged vitamin D-administration to vitamin D-repleted rats led to an intensification of calcium-pyroantimonate deposits and a general increase in total calcium and phosphorus, but no change in the cytosolic Ca2(+)-sensitive enzyme activities. Cessation of vitamin D-administration to vitamin D-repleted rats produced a regression of calcium-pyroantimonate deposits, a general decrease of total calcium and phosphate levels, and stimulation of the Ca2(+)-activated isocitrate-dehydrogenase accompanied by lowering of the Ca2(+)-inhibited pyruvate-kinase. The results clearly indicate a correlation between vitamin D-repletion and the total and bound calcium content of skeletal muscle. In addition, they demonstrate an apparent contradiction between the decrease of total and bound calcium, and the activities of cytosolic Ca2+ sensitive enzymes during vitamin D-deprivation, which can only be explained by an increase in available calcium. It is suggested that vitamin D stimulates intramuscular mechanisms tending to lower available calcium by inactivating the cation via the formation of calcium chelates.


C-Reactive protein reactions to glucose-insulin-potassium infusion and relations to infarct size in patients with acute coronary syndromes.
Some benefits of glucose-insulin-potassium (GIK) in patients with acute coronary syndromes (ACS) may be from an anti-inflammatory effect. The primary aim of this study was to assess the impact of GIK administration early in the course of ACS on inflammatory marker C-reactive protein (CRP) levels. A secondary aim was to investigate the association between CRP and 30-day infarct size. Retrospective analysis of participants with ACS randomly assigned to GIK or placebo for at least 8 h in the IMMEDIATE Trial biological mechanism cohort (n = 143). High sensitivity CRP (hs-CRP) was measured at emergency department presentation, and 6 and 12 h into infusion. Logarithmically transformed hs-CRP values at 12-hours were lower with GIK vs. placebo (mean =0.65 mg/L in GIK, 0.84 mg/L in placebo), with a marginal trend toward significance (P = 0.053). Furthermore, using mixed models of hs-CRP, time, and study group, there was a significant increase in hs-CRP levels over time, but the rate of change did not differ between treatment arms (P = 0.3). Multivariable analysis showed that an elevation in hs-CRP, measured at 12 h, was an independent predictor of 30-day infarct size (β coefficient, 6.80; P = 0.04) using sestamibi SPECT imaging. The results of this study show no significant effect of GIK on hs-CRP. In addition our results show that in patients with ACS, hs-CRP measured as early as 12 h can predict 30-day infarct size.


Association of serum Apolipoprotein B with cerebrospinal fluid biomarkers of Alzheimer's pathology.
To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), or their ratio (ApoB/A1) were associated with early changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology in elderly adults with subjective cognitive decline (SCD). This study included 507 objective cognitive normal participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database including 288 cognitive normal participants (CN) and 219 SCD. Multiple linear regression models were used to examine the associations of apolipoproteins with CSF AD biomarkers. Compared with control group, SCD participants with significant AD biological characteristics had lower ApoB levels (P = 0.0461). In total participants, lower level of serum ApoB was associated with decreases in CSF Aβ42 (P = 0.0015) and Aβ42/40 (P = 0.0081) as well as increases in CSF p-tau/Aβ42 (P < 0.0001) and t-tau/Aβ42 (P = 0.0013), independent of APOEɛ4 status. In further subgroup analysis, these associations were more significant in SCD participants (ApoB × Diagnose: P < 0.05). In addition, lower levels of ApoB were also found associated with increases in p-tau in the SCD subgroup (P = 0.0263). Furthermore, these protective associations were more significant in the overweight participants (ApoB × weight: P < 0.05). Results showed no association between ApoA1 and CSF biomarkers. This study is the first to find protective associations of serum ApoB with CSF AD core biomarkers, especially in SCD individuals. It indicated that ApoB may be a potential biomarker for preclinical AD and may play different roles in different stages of AD.


Vocal fold cancer.
Ninety percent of vocal fold cancers take the form of squamous cell carcinoma. Since the 1980s, incidence in France has been constantly falling in males while increasing in females. The main risk factor is smoking, alcohol being less implicated than in other laryngeal or extralaryngeal locations. Vocal fold squamous cell carcinoma generally develops on healthy mucosa, although primary precancerous lesions such as leukoplakia or papillomatous keratosis are also frequent. The tumor usually originates in the non-lymphophilic mucosal free edge of the vocal fold then invades the various anatomic subunits of the larynx, acquiring lymph-node metastatic potential. Dysphonia is the first presenting symptom, initially caused by defective mucosal vibration and then by impaired mobility and finally fixation of the vocal fold. Extension, risk factor and pretreatment assessments are as in other upper-aerodigestive-tract cancer locations. The possibilities of laryngoscopic exposure and the tumor limits, however, need to be precisely determined if transoral resection is to be considered. For small tumors, surgery or exclusive radiation therapy can be suggested to the patient as part of an individual treatment plan, each having its advantages and drawbacks. Cutting-edge teams report 5-year local control rates of 85-95% in T1-class tumor and 60-90% in T2. Whatever the treatment option, smoking cessation, close surveillance and cardiovascular prevention enable screening of other oncologic locations and limit onset of the other pathologies implicated in most deaths.


Metabolite profiling reveals novel multi-level cold responses in the diploid model Fragaria vesca (woodland strawberry).
Winter freezing damage is a crucial factor in overwintering crops such as the octoploid strawberry (Fragaria × ananassa Duch.) when grown in a perennial cultivation system. Our study aimed at assessing metabolic processes and regulatory mechanisms in the close-related diploid model woodland strawberry (Fragaria vescaL.) during a 10-days cold acclimation experiment. Based on gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) metabolite profiling of three F. vesca genotypes, clear distinctions could be made between leaves and non-photosynthesizing roots, underscoring the evolvement of organ-dependent cold acclimation strategies. Carbohydrate and amino acid metabolism, photosynthetic acclimation, and antioxidant and detoxification systems (ascorbate pathway) were strongly affected. Metabolic changes in F. vesca included the strong modulation of central metabolism, and induction of osmotically-active sugars (fructose, glucose), amino acids (aspartic acid), and amines (putrescine). In contrast, a distinct impact on the amino acid proline, known to be cold-induced in other plant systems, was conspicuously absent. Levels of galactinol and raffinose, key metabolites of the cold-inducible raffinose pathway, were drastically enhanced in both leaves and roots throughout the cold acclimation period of 10 days. Furthermore, initial freezing tests and multifaceted GC/TOF-MS data processing (Venn diagrams, independent component analysis, hierarchical clustering) showed that changes in metabolite pools of cold-acclimated F. vesca were clearly influenced by genotype.


Interaction of the MexA and MexB components of the MexAB-OprM multidrug efflux system of Pseudomonas aeruginosa: identification of MexA extragenic suppressors of a T578I mutation in MexB.
A T578I mutation in MexB compromised the protein's contribution to antimicrobial resistance and negatively impacted its interaction with MexA. Mutations causing single amino acid changes in the C-terminal domain of MexA (R221H, L245F, E254K, and V259I) suppressed the antimicrobial susceptibility of a MexB(T578I)-expressing Pseudomonas aeruginosa strain and restored a MexA interaction with MexB(T578I). These data confirm the importance of the MexA C-terminal region in MexB binding and the likely significance of the region surrounding T587I of MexB in MexA interaction.


Second-harmonic generation from Langmuir-Blodgett film of cyclic peptide carrying two disperse red 1 on fused quartz surface.
Cyclic octapeptide carrying one or two nonlinear optical chromophores, disperse red 1 (DR-1), was synthesized and immobilized on a substrate to attain an active surface for second-harmonic generation (SHG). Each cyclic octapeptide was transferred on a fused quartz substrate by the Langmuir-Blodgett (LB) method to afford a uniform monolayer. Infrared reflection-absorption spectroscopy of the LB monolayer revealed that the cyclic skeleton lay roughly flat on the surface. The SHG intensity from the monolayer of the cyclic peptide with two DR-1 units was stronger than that from that with one DR-1 unit. The difference is discussed in terms of molecular orientation and surface density of the active chromophores. The cyclic peptide is shown here to be an effective scaffold to modify a substrate surface with functional groups of a monolayer with taking stability of the monolayer and orientation of the functional group into consideration.


A pilot study to assess the feasibility of endoscopic placement of a transurethral urinary balloon catheter in male sheep cadavers.
Surgery of obstructive urolithiasis in small ruminants is often unsatisfactory due to postoperative development of strictures. The present study aimed to establish an endoscopic technique for the placement of a transurethral urinary catheter into the bladder of rams. This catheter was used as a removable stent-like drainage. The procedure was performed in three sheep rams that were euthanized and placed for surgery in 45° Trendelenburg position. In one ram, cystotomy was performed via right paramedian laparotomy. A 3 mm flexible fiberscope was introduced into the urinary bladder and advanced via urethra to the tip of the penis. Placing a guide wire through the endoscopic working channel into the urethra enabled the retrograde insertion of a transurethral urinary catheter into the bladder. In two rams, retrograde insertion of a fiberscope was performed. Again, a guidewire was used to insert a balloon catheter into the bladder. Paramedian right laparotomy was performed to ascertain the correct position of the balloon. Both techniques, antero- and retrograde endoscopy, were possible and could be successfully performed. Mucous membranes and urinary microliths were easily observed. Repeated advancing of the endoscope or the catheter resulted in marked damage of the mucous membranes. The patency of the urethra may be restored by means of endoscopic placement of a transurethral catheter in male small ruminants. The applicability and clinical outcome of this procedure as well as the effects on stricture formation should be further examined with controlled clinical studies.


Stimulus ambiguity elicits response conflict.
Conflict monitoring theory [M.M. Botvinick, T. Braver, D. Barch, C. Carter, J.D. Cohen, Conflict monitoring and cognitive control, Psychol. Rev. 108 (2001) 625-652] assumes that perceptual ambiguity among choice stimuli elicits response conflict in choice reaction. It hence predicts that response conflict is also involved in elementary variants of choice reaction time (RT) tasks, i.e., those variants that, by contrast with the Stroop task or the Go/No-Go task for instance, are rarely associated with cognitive control. In order to test this prediction, an experiment was designed in which participants performed a simple RT task and a regular between-hand 2-choice RT task under three different levels of stimulus ambiguity. The data show that response conflict, as measured by the N2 component of the event-related brain potential (ERP), was elicited in the 2-choice RT task but not in the simple RT task and that the degree of response conflict in the 2-choice RT task was a function of stimulus ambiguity. These results show that response conflict is also present in a regular choice RT task which is traditionally not considered to be a measure of cognitive conflict.


Separation of catechin constituents from five tea cultivars using high-speed counter-current chromatography.
Catechins were extracted from five different tea (Camellia sinensis L.) cultivars. High-speed counter-current chromatography was found to be an efficient method for the separation of seven catechins from the catechin extracts. High-performance liquid chromatography was used to assess the purity of the catechins isolated. Epigallocatechin gallate (EGCG), epicatechin gallate (ECG) and epigallocatechin (EGC) of high purity (91-99%) were isolated in high yield after a single high-speed counter-current chromatography run. The two-phase solvent mixtures used for the separation of the catechin extracts were hexane:ethyl acetate:methanol:water (1:6:1:6 for TRI 2023); (1:7:1:7 for TRI 2025 and TRI 2043); (1:5:1:5 for TRI 3079) and (1:6.5:1:6.5 for TRI 4006). Fresh tea shoots from the tea cultivar TRI 2023 (150 g) gave 440 mg of 96% pure EGCG while TRI 2025 (235 g) gave 347 mg of 99% pure EGCG and 40 mg of 97% ECG, and TRI 3079 (225 g) gave 432 mg of 97% pure EGCG and 32 mg of 96% pure ECG. Tea cultivar TRI 4006 (160 g) gave EGCG (272 mg, 96% pure) and EGC (104 mg, 90% pure). 1H and 13C NMR chemical shifts for catechin gallate (CG), EGC, ECG, EGCG and epigallocatechin 3,5-di-O-gallate (EGCDG) in CD3OD were also recorded.


[Off-label therapy of rheumatoid arthritis and spondyloarthritis].
For rheumatoid arthritis (RA) and diseases of the spondyloarthritis group (SpA) a large number of approved medications are available. Nevertheless, in Germany even for these diseases several off-label risks exist for the rheumatologist prescribing antirheumatic drugs which have recently led to a series of recourses or threats of recourse. In RA as well as SpA first of all biologicals are the target of recourse imposed mainly by health insurances. In RA monotherapy (when labeled only in combination with methotrexate), combination with leflunomide (instead of methotrexate) and dose deviations are the most important causes. In SpA TNF inhibitors are labeled only for the definite diagnosis of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) leaving aside patients with severe peripheral spondyloarthritis including enthesitis which does not exactly meet the diagnostic criteria of AS and PsA. The same applies to early AS not fulfilling the 1984 New York criteria which still lacks labeled use of TNF inhibitors. In these cases, however, based on successful randomized controlled trials and changed diagnostic criteria a label extension is expected in the near future. Until then it seems suitable to apply for permission for this treatment from insurers in each case.


The release, absorption and possible health effects of mercury from dental amalgam: a review of recent findings.
Recently many articles have appeared on the subject of mercury from dental amalgam and some of these have questioned its safety as a dental material. This article reviews critically the evidence on mercury release from dental amalgam restorations, its absorption, accumulation and excretion by the body, and its possible relationship to ill-effects. Finally, brief recommendations are given for the handling and usage of dental amalgam.


LncRNA TINCR improves cardiac hypertrophy by regulating the miR-211-3p-VEGFB-SDF-1α-CXCR4 pathway.
Cardiac hypertrophy is a common cardiovascular disease that is found worldwide and is characterized by heart enlargement, eventually resulting in heart failure. Exploring the regulatory mechanism of cardiac hypertrophy is beneficial for understanding its pathogenesis and treatment. In our study, we have showed TINCR was downregulated and miR-211-3p was upregulated in TAC- or Ang II-induced models of cardiac hypertrophy. Dual luciferase and RIP assays revealed that TINCR served as a competitive endogenous RNA (ceRNA) for miR-211-3p. Then, we observed that knockdown of miR-211-3p alleviated TAC- or Ang II-induced cardiac hypertrophy both in vivo and in vitro. Mechanistically, we demonstrated that miR-211-3p directly targeted VEGFB and thus regulated the expression of SDF-1α and CXCR4. Rescue assays further confirmed that TINCR suppressed the progression of cardiac hypertrophy by competitively binding to miR-211-3p, thereby enhancing the expression of VEGFB and activating the VEGFB-SDF-1α- CXCR4 signal. Furthermore, overexpression of TINCR suppressed TAC-induced cardiac hypertrophy in vivo by targeting miR-211-3p-VEGFB-SDF-1α- CXCR4 signalling. In conclusion, our research suggests that LncRNA TINCR improves cardiac hypertrophy by targeting miR-211-3p, thus relieving its suppressive effects on the VEGFB-SDF-1α-CXCR4 signalling axis. TINCR and miR-211-3p might act as therapeutic targets for the treatment of cardiac hypertrophy.


Investigation of predictors of interest in a brief mindfulness-based intervention and its effects in patients with psoriasis at a rehabilitation clinic (SkinMind): an observational study and randomised controlled trial.
Psoriasis (PS) is a chronic inflammatory skin disease accompanied by reduced quality of life. Mindfulness is the ability to focus on the present moment without evaluation. Findings on the effects of 8-week mindfulness trainings in patients with PS reveal positive effects on the severity of the disease and quality of life. However, it remained unclear what distinguishes patients with PS interested in psychological interventions from those without interest and whether also a shorter, namely 2-week mindfulness-based intervention is beneficial in this patient group. This will be investigated with this study. Data will be collected at a rehabilitation clinic in Germany. The study is divided into two parts: study 1a is an observational study. Its aim is to investigate whether sociodemographic, skin-related and psychological factors are significant predictors of interest in a brief psychological intervention in 127 patients with PS. Study 1b is a randomised controlled trial, in which 60 patients (retrieved from study 1a) will be randomised to an intervention or control group (treatment as usual). The main outcome variables are mindfulness and self-compassion. In addition, mediation analyses will be used in an explorative manner to test whether there is a relationship between mindfulness/self-compassion and the severity of PS and whether it is mediated by itch catastrophising and fear of negative evaluation (first model) or perceived stress (second model). The study protocol has been approved by the University of Giessen. Study results will be disseminated by publication of the results at (inter) national conferences and in scientific journals. DRKS00017426 and DRKS00017429.


Morphogenetic clonal growth of kidney epithelial cell line MDCK.
MDCK (Madin-Darby canine kidney) cells were cultured either dispersed within hydrated collagen gel (HCG) or seeded atop a collagen substrate and then immediately overlaid with HCG. Individual cells exhibited clonal growth in three dimensions to form spherical cysts made up of a simple epithelium enclosing a fluid-filled lumen. The cells of MDCK cysts were polarized with the basolateral surface in contact with the collagen gel and the apical surface bordering the lumen. The ultrastructure of MDCK cysts showed similarities to distal nephron. The cells bore apical microvilli and solitary cilia and had occluding junctions and a simple basolateral surface. MDCK cysts increased in size (greater than 800 microns diameter) with continued culture. MDCK cysts grown between layers of HCG were stripped free of the overlying collagen to give direct access to basolateral surface membrane. Unlike monolayer culture, morphogenetic clonal growth of cell line MDCK produces a polarized cell population with a true lumenal and basolateral surface. Collagen-gel-cultured MDCK cysts provide an easily manipulable in vitro cell system that may offer unique advantages for the study of renal cell structure and function.


New insights into 1,2,4-trioxolane stability and the crucial role of ozone in promoting polymer degradation.
Quantum chemical calculations reveal that ozone is capable of instigating a series of degradative processes in poly(methyl methacrylate). The crux lies in the self-decomposition of 1,2,4-trioxolane, which undergoes a spin intersystem crossing process and O-O bond cleavage to unravel a triplet biradical intermediate that facilitates auto-degradation of the polymer chain.


A global survey on occupational health services in selected international commission on occupational health (ICOH) member countries.
The United Nations General Assembly (UNGA), the International Labour Organization (ILO), the World Health Organization (WHO), the International Commission on Occupational Health (ICOH), and the European Union (EU) have encouraged countries to organize occupational health services (OHS) for all working people irrespective of the sector of economy, size of enterprise or mode of employment of the worker. The objective of this study was to survey the status of OHS in a sample of countries from all continents. A questionnaire focusing on the main aspects of OHS was developed on the basis of ILO Convention No. 161 and several other questionnaire surveys used in various target groups of OHS. The questionnaire was sent to 58 key informants: ICOH National Secretaries. A total of 49 National Secretaries responded (response rate 84.5%), from countries that employ 70% of the total world labour force. The majority of the respondent countries, 67%, had drawn up an OHS policy and implement it with the help of national occupational safety and health (OSH) authorities, institutes of occupational health or respective bodies, universities, and professional associations. Multidisciplinary expert OHS resources were available in the majority (82%) of countries, but varied widely in quantitative terms. The average OHS coverage of workers was 24.8%, with wide variation between countries. In over two thirds (69%) of the countries, the content of services was mixed, consisting of preventive and curative services, and in 29% preventive only. OHS financing was organized according to a mixed model among 63% and by employers only among 33% of the respondents. The majority of countries have drawn up policies, strategies and programmes for OHS. The infrastructures and institutional and human resources for the implementation of strategies, however, remain insufficient in the majority of countries (implementation gap). Qualitatively, the content and multidisciplinary nature of OHS corresponds to international guidance, but the coverage, comprehensiveness and content of services remain largely incomplete due to a lack of infrastructure and shortage of multiprofessional human resources (capacity gap). The estimated coverage of services in the study group was low; only a quarter of the total employed population (coverage gap).


Conversation Initiation of Mothers, Fathers, and Toddlers in their Natural Home Environment.
In a conversational exchange, interlocutors use social cues including conversational turn-taking to communicate. There has been attention in the literature concerning how mothers, fathers, boys, and girls converse with each other, and in particular who initiates a conversation. Better understanding of conversational dynamics may deepen our understanding of social roles, speech and language development, and individual language variability. Here we use large-scale automatic analysis of 186 naturalistic daylong acoustic recordings to examine the conversational dynamics of 26 families with children about 30 months of age to better understand communication roles. Families included 15 with boys and 11 with girls. There was no difference in conversation initiation rate by child sex, but children initiated more conversations than mothers, and mothers initiated more than fathers. Results support developmental theories of the different and variable roles that interlocutors play in a social context.


Effect of K-line on posterior cervical surgery in patients with posterior longitudinal ligament ossification.
To evaluate the effect of K-line on posterior single-door decompression with fusion fixation (PFF) and posterior single-door decompression with non-fusion fixation (PNF) for patients with ossification of posterior longitudinal ligament (OPLL). A total of 65 patients with OPLL were analyzed retrospectively. They consisted of 44 patients with positive K-line, designated as the K ( +) group, and 21 patients with negative K-line, designated as K (-). The patients were also divided into a PFF group (38 patients) and a PNF group (27 patients). The Japanese Orthopaedic Association (JOA) score, C2-C7 Cobb angle, improvement rate of JOA score, and complications were calculated and statistically analyzed between the groups. In the K ( +) group, there were no significant differences in the incidence of C5 nerve root palsy and C2-C7 Cobb angle between the two groups of surgical patients, but there were significant differences in the improvement rate of JOA score and the incidence of axial pain. In the K (-) group, there were no significant differences in the incidence of axial pain, the incidence of C5 nerve root palsy, and preoperative C2-C7 Cobb angle between the two groups, but significant differences were observed in the improvement rate of JOA score and C2-C7 Cobb angle at the last follow-up. In the K ( +) group, the improvement rate of JOA score was higher and the incidence of axial pain was lesser in the PNF group than in the PFF group. In the K (-) group, the improvement rate of JOA score was higher in the PFF group than in the PNF group, and there was significant loss of C2-C7 Cobb angle in the PNF group.


Effect of magnesium ions on the high-affinity binding of eosin to the (Na+ + K+)-ATPase.
(1) The fluorescence of eosin Y in the presence of (Na+ + K+)-ATPase is enhanced by Mg2+. The enhancement by Mg2+ is larger than that obtained with Na+ (Skou, J.C. and Esmann, M. (1981) Biochim. Biophys. Acta 647, 232-240). Mg2+ shifts the excitation maximum from 518 to 524 nm, the emission maximum from 538 to 542 nm. Also a shoulder appears at about 490 nm on the excitation curve, as was also observed with Na+. (2) The Mg2+-dependent enhancement of fluorescence can be reversed by K+ as well as by ATP. In the presence of Mg2+ + Pi (i.e. under conditions of phosphorylation), the fluorescence enhancement can be reversed by ouabain. With Mg2+ and a low concentration of K+ (i.e. conditions for vanadate binding), the enhancement of fluorescence can be reversed by vanadate. (3) There is a low-affinity binding of eosin which increases with the Mg2+ concentration. This is observed as a slight increase in the fluorescence when the excitation wavelength is above 520 nm. The low-affinity binding is K+-, ATP-, ouabain- and vanadate-insensitive. (4) Scatchard analysis of the binding experiments suggests that there are two high-affinity eosin-binding sites per 32P-labelling site in the presence of 5 mM Mg2+ both of which are ouabain-, vanadate- and ATP-sensitive. With 5 mM Mg2+ + 0.25 Pi, the Kd values are 0.14 microM and 1.3 microM, respectively. With 5 mM Mg2+, 150 mM Na+, the Kd values are 0.45 microM and 3.2 microM, respectively. With 5 mM Mg2+, the addition of K+ gives a pronounced decrease in affinity but does not decrease the number of binding sites (which remains at two per 32P-labelling site). With 5 mM Mg2+ + 150 mM K+, the affinities of the two binding sites become identical, at a Kd of 17 microM. (5) The rate of conformational transitions was measured using the stopped-flow method. The rate of the transition from the Mg2+-form to the K+-form is high. Oligomycin has only a small (if any) effect on the rate. Addition of Na+ in the presence of Mg2+ does not appreciably change the rate of conversion to the K+-form, giving a rate constant of about 110 s-1. However, the addition of oligomycin in the presence of Mg2+ + Na+ had a profound effect: the rate of conversion to the K+-form was decreased by a factor of 2000 to about 0.063 s-1. This suggests that the conformation with Mg2+ alone is different from the conformation with Na+ alone. (6) The effects of K+, ouabain, vanadate and ATP on the high-affinity binding of eosin suggest that the two eosin molecules bound per 32P-labelling site are bound to ATP sites.


Wound complications at the groin after peripheral arterial surgery sparing the lymphatic tissue: a double-blind randomized clinical trial.
The groin incision after arterial reconstructive surgery is most likely at risk for infectious or lymphatic wound complications. Theoretically; sparing lymphatic tissue by a lateral approach to the femoral artery should minimize these. The aim of this study was to assess the incidence of wound complications after the lateral versus the direct approach of the common femoral artery. The study population included all patients who underwent an exploration of the common femoral artery between May 2002 and December 2005. After 6 weeks, no statistical differences in the occurrence of wound complications could be shown. A wound infection was present after 6 weeks in 6.1% in the direct group versus 6.0% in the lateral group. Lymphorrhea was persistent in 3.1% in the direct group versus 5.0% in the lateral group. Using a lateral vertical incision for the approach of the common femoral artery did not decrease the incidence of postoperative wound complications.


Kids and cocaine--a treatment dilemma.
Despite aggressive efforts to recruit into treatment cocaine users 21 years and younger, we obtained only 12 such clients over a period of 9 months, while recruiting 122 adult cocaine clients during a comparable time frame. An examination of admissions data for the city, state, and nation indicated that our experience was typical. However, data from the most recent national household survey indicate that, to the extent need for treatment is determined by frequency of cocaine use, we should anticipate a much greater proportion of admissions to treatment to come from persons 21 years of age and younger. Yet, there appears to be an under-recruitment of youth into treatment, particularly evidenced by low rates of self-referral for juvenile as compared to older treatment admissions. Younger cocaine users may be less severely impaired and/or dependent, or may be more reluctant to use the treatment resources available. Whatever the barriers are to getting help, it becomes the special task of agencies and individuals in the community to help assure that younger cocaine users will obtain the assistance they need. Four community resources are seen as particularly relevant: family, schools, the medical community, and public agencies in the areas of health, social services, and criminal justice. The capacity of each to take action and possible impediments to that action are discussed.


Validity of 99mTc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function.
99mTc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a 131I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. 99mTc dimercaptosuccinic acid scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.


Trace analysis of mono-, di-, tri-substituted polyfluoroalkyl phosphates and perfluorinated phosphonic acids in sewage sludge by high performance liquid chromatography tandem mass spectrometry.
A new method using ultrasonic extraction and solid phase extraction (SPE) clean-up pretreatments was developed for the analysis of mono-, di- and tri-substituted polyfluoroalkyl phosphates (abbreviated as mono-PAPs, di-PAPs and tri-PAPs) and perfluorinated phosphonic acids (PFPAs) in sludge from wastewater treatment plants (WWTPs). For the ultrasonic extraction of three mono-PAPs, three di-PAPs and three PFPAs in sludge samples, a mixture of tetrahydrofuran/acetic acid (1:1, v/v) was found to be the most suitable extraction solvent. The subsequently optimized clean-up and enrichment procedures were carried out with weak anion exchange (WAX) cartridges in-line coupled with graphitized carbon black (ENVI-Carb) tubes. Two tri-PAPs were ultrasonically extracted by acetonitrile/tetrahydrofuran (1:1, v/v) and cleaned by mixed-mode anion exchange (MAX) in-line coupled with ENVI-Carb cartridges. The analytes were analyzed by optimized high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method either in negative or positive ionization mode. The method quantification limits (MQLs) of the 11 analytes in sludge ranged from 0.6 to 5.1 ng/g, meanwhile the total recoveries of the pretreatment varied from 24% (6:2 mono-PAP) to 107% (PFDPA). The method was successfully applied to analyze 16 sewage sludge samples collected from seven provinces in China, and two mono-PAPs were identified with concentrations ranging from <MQLs to 10.7 ng/g.


[Prognostic indices for older adults during the year following hospitalization in an acute medical ward: An update].
As population grow older, chronic diseases are more prevalent. It leads to an increase of hospitalization for acute decompensation, sometimes iterative. Management of these patients is not always clear, and care provided is not always proportional to life expectancy. Making decisions in acute situations is not easy. This review aims to list and describe mortality scores within a year following hospitalization of patients of 65 years or older. Following keywords were searched in title and abstract of articles via an advanced search in PudMed, and by searching Mesh terms: "aged", "aged, 80 and over", "mortality", "prognosis", "hospitalized", "models, statistical", "acute geriatric ward", "frailty", "outcome". Studies published in English between 1985 and 2015 were selected. Last article was published in June 2015. Articles that described prognostic factors of mortality without a scoring system were excluded. Articles that focus either on patients in the Emergency Department and in Intensive Care Unit, or living in institution were excluded. Twenty-two scores are described in 17 articles. These scores use items that refer to functional status, comorbidities, cognitive status and frailty. Scores of mortality 3 or 6 months after hospitalization are not discriminative. Few of the 1-year mortality prognostic score are discriminative with AUC≥0.7. This review is not systematic. Practical use of these scores might help management of these patients, in order to initiate appropriate reflexion and palliative care if necessary.


[Choice of restorative materials in posterior Class V cavities].
Microleakage of class V restorations in posterior teeth was studied, using different types of materials and cavity varnish. Significantly less microleakage was recorded by applying some layers of cavity varnish and using spherical alloy.


American tegumentary leishmaniasis: cytokines and nitric oxide in active disease and after clinical cure, with or without chemotherapy.
The influence of immune response on the treatment of American tegumentary leishmaniasis is pointed by several authors, and the existence of protective immunity in self-healed patients (SH) is also suggested. Thus, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), interleukin (IL-) 10, IL-17, IL-22 and nitric oxide (NO) production was determined in PBMC culture supernatants from patients with active disease (AD) and after therapy, SH patients and healthy subjects, in response to the soluble antigen of Leishmania (Viannia) braziliensis. It was demonstrated that, during the active disease, there is a predominance of IFN-γ and TNF-α, indicating a proinflammatory phase of the response; IL-17 is also highlighted at this clinical state. Also, TNF-α was slightly increased in patients after therapy. NO secretion was noticed in SH individuals, while IL-17 appeared in low levels in these patients and seems to be regulated by NO. The presence of IL-10 was observed in all groups of patients. From this study, we can suggest that in the active disease and after clinical cure, with or without chemotherapy, specific cellular immunity takes part against Leishmania, but with some similarities between the clinical states. Thus, it indicates that the mediators herein described are necessary for the cure to occur.


An All-Organic Self-Powered Photodetector with Ultraflexible Dual-Polarity Output for Biosignal Detection.
Endowing photodetectors with mechanically flexibility and actual functionality are current research issues in developing optoelectronic devices. However, rigid metal-based or metal-oxide-based electrodes remain a block to the realization of ultraflexible electronics. Thus, an ultraflexible all-organic photodetector (all-OPD) is designed by innovatively introducing symmetrical organic electrodes PH1000/PH1000 to substitute the widely applied indium-doped tin oxide (ITO)/Ag electrodes. Specifically, this all-OPD exhibits a high self-powered responsivity (R) of over 100 mA W-1 among 500-600 nm and the photocurrent remains about 80% of the original performance after being bent 20 000 circles, and can output steady biosignals for photo-plethysmography (PPG) application. More importantly, this all-OPD outputs dual-polarity photocurrent as it is flipped or folded. Benefitting from the ordered phase distribution and designed Schottky barrier heights, the photogenerated holes will be transferred and collected by nearer electrode, while electrons will be trapped in the thick bulk heterojunction (BHJ) as a result of the long channel. This work offers a new avenue toward developing a multifunctional and ultraflexible all-OPD with a straightforward all-solution method, and it is expected to be more compatible in complex application scenarios.


A rare case of benign pneumatosis intestinalis in Sjogren's syndrome.
Pneumatosis intestinalis (PI)-the presence of intramural bowel gas-is an uncommon radiological finding, the severity of which depends on the underlying pathological process, ranging from benign disease to life-threatening ischaemia and intra-abdominal sepsis. PI has been described in systemic sclerosis and mixed connective tissue disease; however, few cases have been reported in Sjogren's syndrome (SjS). The exact pathogenesis of PI in systemic connective tissue disorders is not fully understood and likely multifactorial. We have described a unique case of PI without evidence of peritonitis in a stable patient with long-standing SjS managed non-operatively. An awareness of such benign PI, particularly amongst patients with systemic connective tissue disease, is crucial for diagnostic accuracy and safe patient care, particularly in preventing unnecessary surgical intervention.


Exploration of retinoid activity and the role of inflammation in acne: issues affecting future directions for acne therapy.
The review summarizes new results concerned with several important issues in the treatment of patients with acne. The first section reviews studies which show that 13-cis retinoic acid, a molecule with strong biological activity but low binding affinity for retinoid receptors and cellular-binding proteins in sebocytes, undergoes rapid intracellular conversion to all-trans retinoic acid. This active metabolite exerts its actions on sebocyte gene expression by binding to the nuclear retinoic acid receptor rather than the retinoid X receptor. Importantly, 13-cis retinoic acid, unlike all-trans retinoic acid, does not induce cytochrome P450 1A1, an enzyme responsible for the metabolism of xenobiotics. Thus, administration of 13-cis retinoic acid permits high long-term intracellular accumulation of its active metabolite. The second section reviews studies which suggest that leukotriene B4 may play a key role in acne-related inflammation. Results from a preliminary clinical study indicate that therapy with a specific lipoxygenase inhibitor is clinically effective in the treatment of patients with inflammatory acne and that its clinical efficacy is correlated with the drug's ability to reduce total lipid levels, and especially pro-inflammatory lipids, in sebum. Interestingly, 13-cis retinoic acid has been shown to modulate the activities of LTB4 and inflammatory events in the development of acne. Therefore, future compounds targeting acne have to inhibit pro-inflammatory lipids in sebum, and thus down-regulate acne-related inflammatory signals and reduce the LTB4-induced migration of inflammatory cells.


Development of the Diatom Ecological Quality Index (DEQI) for peri-urban mountain streams in the Basin of Mexico.
In the Basin of Mexico, one of the most important economic regions in the country with over 22 million inhabitants, peri-urban streams have been transformed into sewers, drains, and pipes to avoid flooding or unsanitary conditions; the change affects not only the ecosystem's goods and services but also the aquatic communities that support the natural ecological processes. We aimed to develop a diatom-based diagnosis of the ecological quality of these aquatic ecosystems through the study of epilithic diatom response to regional environmental gradients. Samples of epilithic diatoms and water were collected in 45 sites representing 12 perennial streams, and multivariate analyses were performed on environmental and biological data. The ecological quality gradient to which diatoms responded was related to oxygen saturation, soluble reactive phosphorous, dissolved inorganic nitrogen, and hydromorphological quality. Three species groups were recognized according to their ecological preferences along CCA1 axis, indicators of high and low ecological quality, and tolerant species. By assigning an indicator value to each species group, we calculated the DEQI using the formula adapted from Pantle and Buck, indicating five different ecological quality classes. This index is proposed for complementing the ecological quality evaluation as a biological metric that responds to multiple regional stressors of the structure and function of these peri-urban streams in the Basin of Mexico.


Transcriptional response of a green alga (Raphidocelis subcapitata) exposed to triclosan: photosynthetic systems and DNA repair.
Recent studies show that triclosan (TCS) exposure causes reduction in pigments, suppression of photosynthesis, and induction of oxidative stress at the physiological level, resulting in morphological alteration and growth inhibition in algae including Raphidocelis subcapitata (R. subcapitata, a freshwater model green alga). However, the underlying molecular mechanisms remain to be elucidated, especially at environmentally relevant concentrations. The present study uncovered the transcriptional profiles and molecular mechanisms of TCS toxicity in R. subcapitata using next-generation sequencing. The algal growth was drastically inhibited following a 7-day exposure at both 75 and 100 μg/L TCS, but not at 5 μg/L (environmentally realistic level). The transcriptomic analysis shows that molecular signaling pathways including porphyrin and chlorophyll metabolism, photosynthesis - antenna proteins, and photosynthesis were suppressed in all three TCS treatments, and the perturbations of these signaling pathways were exacerbated with increased TCS exposure concentrations. Additionally, signaling of replication-coupled DNA repair was only activated in 100 μg/L TCS treatment. These results indicate that photosynthesis systems were sensitive targets of TCS toxicity in R. subcapitata, which is distinct from the inhibition of lipid synthesis by TCS in bacteria. This study provides novel knowledge on molecular mechanisms of TCS toxicity in R. subcapitata.


Analysis of outcomes following loop electrosurgical excision and clinical features of patients with cervical high-grade squamous intraepithelial lesions with abnormal preoperative endocervical curettage.
The purpose of this study was to identify the clinical characteristics of patients with high-grade squamous intraepithelial lesions (HSIL) with abnormal endocervical curettage (ECC) and to evaluate the efficacy of abnormal preoperative ECC in predicting recurrence after a loop electrosurgical excision procedure (LEEP). We retrospectively analyzed a total of 210 cases of histological HSIL in female patients diagnosed using cervical biopsy and/or indiscriminating ECC, and these included 137 cases with normal ECC and 63 cases with abnormal ECC. We also collected preoperative information and data on postoperative human papillomavirus (HPV) and histological outcomes within 2 years. The additional detection rate of HSIL using indiscriminating ECC was 5%. Patients with abnormal ECC were older (P < 0.001), predominantly menopausal (P = 0.001), had high-grade cytology (P = 0.032), a type 3 transformation zone (P = 0.046), and a higher proportion of HPV type 16/18 infection (P = 0.023). Moreover, age (odds ratio [OR] = 1.078, 95% confidence interval [CI] = 1.0325-1.1333, P = 0.003) and HPV 16/18 infection (OR = 2.082, 95% CI = 1.042-4.2163, P = 0.038) were independent risk factors for abnormal ECC. With an observed residual lesion/recurrence rate of 9.5% over the 24-month follow-up, we noted a 9.3% higher rate in the abnormal ECC group when compared with the normal ECC group. Abnormal preoperative ECC (OR = 4.06, 95% CI = 1.09-15.14, P = 0.037) and positive HPV at the 12-month follow-up (OR = 16.55, 95% CI = 3.54-77.37, P = 0.000) were independent risk factors for residual disease/recurrence. Preoperative ECC was one of the risk factors for post-LEEP residual/recurrent HSIL, and detecting abnormal ECC when managing older patients or patients with HPV 16/18 infection during colposcopy is critical.


Effects of disruption of microtubules on translocation of particles and morphology in tissue cultured neurites.
The role of microtubules in axoplasmic transport was studied by using colchicine and vinblastine in tissue cultured dorsal root ganglion cells dissected from chick embryos. After 3-4 days in culture, the effects of the agents on particle movement were examined under Nomarski optics. The movements of the particles were analyzed with high-contrast video systems. The number of transported particles passing through one region decreased after exposure to colchicine or vinblastine in concentrations greater than 1 X 10(-7) M, but these agents did not affect the velocity of the transported particles. After treatment with the agents swelling occurred in regions where particles sometimes stopped or slowed down in normal conditions. The intervals between swollen regions were 5-25 micron and transported particles finally stopped in the swollen regions. After 1 h of treatment with 1 X 10(-5) M colchicine, electron micrographs showed many organelles but no microtubules in the swollen regions. It is thought from these results that the disruption of microtubules in neurites might occur at the ends of the microtubules, followed by swellings in the neurites and particle transport blockade, but the morphological change itself might not have an effect on the transport of particles.


The initial suppression of bacterial growth in a salmonella infection is mediated by a localized rather than a systemic response.
Mice were infected intravenously with two antibiotic resistance tagged variants of the same S. typhimurium strain given in close succession, or simultaneously with strains of different virulence. The first manifestation of acquired resistance--suppression of exponential bacterial growth in liver and spleen--occurred independently for the different strains in the same individuals, implying that it is due to localized rather than systemic events. This early suppression of bacterial growth was ablated by whole body X-irradiation (800R), whereas the immediately preceding phase of exponential growth (Ity controlled innate resistance) was not affected. Transfer of spleen cell suspensions from infected mice into syngeneic recipients conferred protection by suppressing the growth of an intravenous challenge. Pre-treatment of the suspensions to deplete them of macrophages abolished their protective capacity, while depletion of T-cells did not. Mice deficient in T-cells by adult thymectomy and anti-T-cell monoclonal antibody treatment were able to suppress the growth of an intravenous challenge. Taken collectively, the present data show that the very early phase of acquired resistance to salmonellae, essential for survival, is not the result of systemically developing resistance but a localized event at the site of infection.


Comment on "Should we reframe how we think about physical activity and sedentary behavior measurement? Validity and reliability reconsidered".
With great interest we read the article by Kelly et al. on the measurement of physical activity (PA) and sedentary behavior (SB) (Kelly P et al. Int J Behav Nutr Phys Act 13:(1) 32, 2016). We appreciate the invitation of the authors to provide feedback on their ideas and we take this opportunity to contribute to the discussion. Our main proposition is that this field can learn much from the field of quality of life research and the methodology developed for validating quality of life questionnaires.


Progesterone inhibition of aggressive behaviors in hamsters.
Effects of progesterone on aggressive behaviors were tested in male-male or female-female pairs of hamsters, after both members of the pair had received the same experimental treatment. In castrated males, progesterone increased the latency to attack, and decreased the frequency of attack and on-back fighting postures. Similarly, in ovariectomized females, progesterone decreased the frequencies of upright and attack fighting responses, as well as the frequency of rolling fights. Estradiol treatment did not produce these effects on aggressive behaviors, and was not required to prime the nervous system for the progesterone effects. These results suggest that progesterone may act by means other than estrogen-inducible progestin receptors to inhibit aggressive behaviors.


Extending the golden hour of hemorrhagic shock tolerance with oxygen plus hypothermia in awake rats. An exploratory study.
In a previous study of volume-controlled hemorrhagic shock (HS) in awake rats, without fluid resuscitation, either breathing of 100% oxygen or moderate hypothermia while breathing air, increased survival time. We hypothesized that combining oxygen and hypothermia can maximally extend the "golden hour" of HS from which resuscitation can be successful in terms of survival rate. Rats were prepared under light general anesthesia, breathing spontaneously via face mask, and then awakened for 2 h. Then, 3.25 ml arterial blood/100 g were withdrawn over 20 min. At the end of HS of 30, 60, 90 or 180 min duration, the shed blood was reinfused. Breathing was spontaneous. Survival endpoint was 24 h or earlier death. HS of 30 or 60 min was used for preliminary experiments; HS of 90 or 180 min for 35 definitive experiments. Control groups A-1 and B-1 had normothermia (rectal temperature 37.5 degrees C) and were breathing air. Treatment groups A-2 and B-2 had total body surface cooling during HS to rectal temperature 32 degrees C and were breathing 100% O(2). Arterial pressure during HS was higher in the hypothermia-O(2) groups. With HS of 90 min, in the normothermia-air group A-1 (n=10), none of the 10 rats survived to 3 h; while in the hypothermia-O(2) group A-2 (n=5), all rats survived to 24 h (P<0.001). With HS of 180 min, in the normothermia-air group B-1 (n=10), three of 10 rats survived to 3 h and 24 h (hypotension during HS in these three survivors was less severe than in the non-survivors); and in the hypothermia-O(2) group B-2 (n=10) all 10 rats survived to 24 h (P<0.003). We conclude that moderate hypothermia (32 degrees C) plus 100% oxygen inhalation during volume-controlled HS in awake rats mitigates hypotension and increases the chance of survival. It enables survival even after 3 h of moderate HS.


Resolving Halide Ion Stabilization through Kinetically Competitive Electron Transfers.
Stabilization of ions and radicals often determines reaction kinetics and thermodynamics, but experimental determination of the stabilization magnitude remains difficult, especially when the species is short-lived. Herein, a competitive kinetic approach to quantify the stabilization of a halide ion toward oxidation imparted by specific stabilizing groups relative to a solvated halide ion is reported. This approach provides the increase in the formal reduction potential, ΔE°'(Χ•/-), where X = Br and I, that results from the noncovalent interaction with stabilizing groups. The [Ir(dF-(CF3)-ppy)2(tmam)]3+ photocatalyst features a dicationic ligand tmam [4,4'-bis[(trimethylamino)methyl]-2,2'-bipyridine]2+ that is shown by 1H NMR spectroscopy to associate a single halide ion, K eq = 7 × 104 M-1 (Br-) and K eq = 1 × 104 M-1 (I-). Light excitation of the photocatalyst in halide-containing acetonitrile solutions results in competitive quenching by the stabilized halide and the more easily oxidized diffusing halide ion. Marcus theory is used to relate the rate constants to the electron-transfer driving forces for oxidation of the stabilized and unstabilized halide, the difference of which provides the increase in reduction potentials of ΔE°'(Br•/-) = 150 ± 24 meV and ΔE°'(I•/-) = 67 ± 13 meV. The data reveal that K eq is a poor indicator of these reduction potential shifts. Furthermore, the historic and widely used assumption that Coulombic interactions alone are responsible for stabilization must be reconsidered, at least for polarizable halogens.


Septa within the sinus: effect on elevation of the sinus floor.
Elevation of the sinus floor allows the correct number and length of oral implants to be placed. The sinus membrane is dissected blindly, usually by a crestal approach, but several internal configurations of the maxillary sinus or intrasinus septa can cause problems. We studied 150 sinuses from 40 male cadavers, and 35 randomised male patients by anatomical dissection and computed tomography. Forty-six subjects (61%) had no bony septa or had septa less than 4mm. Twenty-nine (39%) had bony septa of which seven were incomplete, one had a complete bony septum in each maxillary sinus, and 20 had symmetrical bony septa. We present the results of a study of bony intramaxillary sinus septa and the potential problems they can cause during elevation of the sinus floor.


In vivo profiling of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced estrogenic/anti-estrogenic effects in female estrogen-responsive reporter transgenic mice.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to simply as "dioxin", is a persistent environmental pollutant. Because of its high environmental persistence and biological accumulation, humans and animals are often exposed to TCDD. Therefore, the harmful effects on humans and animals is a major concern. Although studies have elucidated the adverse estrogenic and anti-estrogenic effects of TCDD, it is unclear in which tissues TCDD exerts these effects in vivo. To investigate the estrogen-related effects of TCDD in various tissues, we generated an improved estrogen-responsive reporter transgenic mouse in which the luciferase gene luc2 is expressed in response to estrogenic signals. Using these mice, we clarified that TCDD inhibits estrogenic signaling in liver and kidney but enhances estrogenic signaling in the pituitary gland in the same individual. Expression of aryl hydrocarbon receptor, aryl hydrocarbon receptor nuclear translocator, and estrogen receptor alpha mRNA was detected in liver, kidney, and pituitary gland, suggesting that the effects of TCDD on estrogenic signaling in these organs is independent of the expression pattern of these receptors. Thus, our results indicate that TCDD exerts both estrogenic and anti-estrogenic tissue-specific effects within the same individual.


Cholinergic toxic syndrome by the anticancer drug irinotecan: acetylcholinesterase does not play a major role.
The anticancer drug irinotecan induces cholinergic side effects that are currently ascribed to the blockade of acetylcholinesterase. This study investigated (1) the pattern of acetylcholinesterase activity in patients receiving treatment with irinotecan and (2) the relationship between acetylcholinesterase activity and plasma concentrations of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), and SN-38 glucuronide (SN-38G). Twenty-five patients with advanced colorectal cancer were treated with 250 mg/m(2) irinotecan administered by intravenous infusion for 60 minutes. Blood samples were collected before drug infusion and at 15 minutes and 45 minutes after the start of drug infusion. Blood acetylcholinesterase activity was determined by a colorimetric enzymatic assay, and irinotecan, SN-38, and SN-38G concentrations were determined in plasma by HPLC. The in vitro effects of irinotecan and other drugs on human acetylcholinesterase were also assessed. Compared with basal values, the activity of acetylcholinesterase in blood specimens collected during irinotecan infusion at 15 minutes (-0.76%) and at 45 minutes (-1.50%) showed no changes. No relationships were established between the activity of blood acetylcholinesterase at 15 or 45 minutes and plasma concentrations of irinotecan, SN-38, or SN-38G measured at the same time points. In vitro, the activity of acetylcholinesterase was inhibited by 100-micromol/L irinotecan (-24.8%) and markedly reduced by 1-micromol/L physostigmine (-86.7%), whereas neither SN-38 nor camptothecin had an effect. Although the use of erythrocyte acetylcholinesterase as a surrogate marker of acetylcholinesterase activity in the nervous system has not been firmly established, our findings do not support the hypothesis that the toxic cholinergic syndrome associated with irinotecan treatment depends on acetylcholinesterase blockade.


Bilateral sixth cranial nerve palsy, the first presenting feature of hemorrhagic apoplexy of pituitary macroadenoma: A case report.
We report on apoplexy of undiagnosed pituitary macroadenoma presenting as sudden onset bilateral sixth nerve palsy. A 36-year-old male patient presented with a complaint of sudden onset diplopia for one week associated with chronic headache for two years. On further investigations, isolated bilateral sixth cranial nerve palsy was found to cause diplopia in lateral gaze and at distance. Magnetic resonance imaging of the brain showed a well-defined lobulated mass of 19 × 22 × 24 mm in the sellar and suprasellar region with hemorrhage, compressing optic chiasma superiorly with extension into the superior cavernous sinus compartment on the left side. The neurosurgery team excised the tumour through an endoscopic endonasal transsphenoidal approach. Abducens nerve palsy recovered within one week. In our case diplopia due to bilateral sixth cranial nerve palsy was the first clinical presentation of hemorrhagic apoplexy of pituitary macroadenoma which is a potentially life-threatening condition. There was no other significant ocular symptoms. High index of suspicion, prompt diagnosis and multidisciplinary team management resulted into favourable outcome. Sudden onset diplopia and isolated bilateral sixth nerve palsy should be added to the spectrum of clinical presentations of hemorrhagic apoplexy of previously undiagnosed pituitary macroadenoma.


Application of the maximum likelihood principle to separate exponential terms in T2 relaxation of nuclear magnetic resonance.
The method of maximum likelihood has been implemented for the estimation of multiple exponential components of T2 decay curves in spin echo NMR measurements on biologic tissues. Each Each component contributes an exponential term described by two parameters (initial amplitude and T2) to the T2 decay curve. The maximum likelihood method estimates the parameters and their standard errors for all terms simultaneously, avoiding the subjectivity inherent in methods such as graphical peeling. In the model used, it was assumed that water protons are compartmentalized and that the measured spin echo signals from the protons undergoing relaxation obey the Poisson distribution. A system of non-linear equations was derived and solved iteratively for the values of the exponential parameters which maximize the likelihood of obtaining the observed data under these assumptions. The approach was implemented for bi- and tri-exponential models on a MicroVAX II computer (Digital Equipment Corporation, Maynard, MA). Simulations of bi- and tri-exponential data, with and without system noise, were analyzed to assess the accuracy and reproducibility of the method. A subset of the simulations was repeated with non-linear least squares techniques and was compared to the results obtained with maximum likelihood. Rabbit muscle and gerbil brain samples were measured and analyzed with the maximum likelihood method. The simulations showed that within specific limits on relative sizes and relaxation rates of components, these parameters can be estimated with errors less than 5%. The comparison to non-linear least squares analysis showed that the maximum likelihood method is generally superior in estimating the parameters in difficult cases. The results from tissue measurements demonstrate that the method is effective even in cases where graphical peeling would clearly not yield reliable results.


Mammary amylase: a possible alternate pathway of carbohydrate digestion in infancy.
Mammary amylase is a possible alternate pathway of digestion of glucose polymers and starches, that is most important in early infancy when pancreatic amylase is low or absent in duodenal fluid and responds poorly to stimuli. Human breast milk contains 1000-5000 units of amylase/liter. In order to evaluate the likelihood that a significant proportion of mammary amylase activity would withstand passage through the stomach, purified and unpurified mammary amylase were exposed to acid and pepsin in vitro to simulate the gastric environment found in young infants. Both purified and unpurified enzymes were stable at pH 7.5 with little or no activity lost after 4 h, and approximately 80% retained at 6 h. When incubated at pH 3.5, one-third of unpurified enzyme activity was retained for 6 h; in contrast, the purified enzyme was acid labile losing 80% by 2 h. Addition of bovine serum albumin or breast milk proteins to purified enzyme protected the activity. When unpurified enzyme was exposed to a stepwise decline in pH from 6.5 to 3.5 over 4 h, 50% of the original activity was retained. Unless the concentration was greater than or equal to 3750 units/ml, the addition of varying concentrations of pepsin to defatted breast milk incubated at pH 3.5 did not affect any greater decay of enzyme activity despite evidence of peptic digestion of proteins in the reaction mixture. This study supports the possibility that ingested mammary amylase could retain a significant proportion of its original activity after exposure to acid and pepsin in the stomach of young infants.


The neglected coronary atherosclerosis.
A study of the natural history of coronary heart disease by means of gross inspection and light microscopy, carried out on 640 subjects aged 1-50 years who had died of violent accidents, revealed a grossly neglected coronary atherosclerosis. It included fibromuscular plaques, intimal necrotic areas and incorporated microthrombi present in the longitudinally opened main coronary arteries but not visible to the naked eye, and some atherosclerotic lesions visible to the naked eye but present in branch vessels unopened or not removed during routine autopsy. There were approximately 500 grossly neglected intimal necrotic areas and approximately 120 grossly neglected incorporated microthrombi; from a total of 809 atherosclerotic plaques 261 (32%) were grossly neglected. The topographic distribution and the number of neglected and non-neglected atherosclerotic plaques, in successive age groups, were analyzed. A small subsample, including 32 patients 52-79 years old, dead of coronary heart disease, was used to demonstrate the importance of the detection of obstructive atherosclerotic lesions in some usually unopened or not removed branch vessels for a realistic anatomo-clinic-cardioangiographic and ECG correlation.


Length of hydrocarbon chain influences location of curcumin in liposomes: Curcumin as a molecular probe to study ethanol induced interdigitation of liposomes.
Using fluorescence quenching of curcumin in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes by brominated derivatives of fatty acids, the location of curcumin has been studied, which indicates length of hydrocarbon chain has an effect on the location of curcumin in liposomes. Change of fluorescence intensity of curcumin with temperature in the presence of liposomes helps to estimate the phase transition temperature of these liposomes, thus, influence of cholesterol on liposome properties has been studied using curcumin as a molecule probe. The cooperativity due to the interactions between the hydrocarbon chains during melting accelerates the phase transition of DPPC liposomes in the presence of high percentage of cholesterol whereas high percentage of cholesterol generates a rather rigid DMPC liposome over a wide range of temperatures. We used ethanol to induce interdigitation between the hydrophobic chains of the lipids and studied this effect using curcumin as fluorescence probe. As a result of interdigitation, curcumin fluorescence is quenched in liposomes. The compact arrangement of the acyl chains prevents curcumin from penetrating deep near the midplane. In the liquid crystalline phase ethanol introduces a kind of order to the more fluid liposome, and does not leave space for curcumin to be inserted away from water.


Truncus arteriosus communis with interrupted aortic arch: successful repair using a novel technique.
We report a successful one-stage biventricular repair of truncus arteriosus communis with interrupted aortic arch in a neonate. This newborn girl was diagnosed with truncus arteriosus communis type III-B (Congenital Heart Surgeons Society classification) by the echocardiography and three-dimensional computed tomography. We present a new reconstructive approach for such heart defects, involving a modified Lecompte maneuver combined with arch reconstruction, by suturing the ascending aorta to the descending aorta in end-to-end fashion called the swing-back technique.


Immunoglobulin variable region sequences of human monoclonal anti-DNA antibodies.
Anti-DNA antibodies are believed to be important in the pathogenesis of systemic lupus erythematosus (SLE). Antibodies that bind specifically and with high affinity to dsDNA are most closely involved in tissue damage. Analysis of the sequences of the variable regions of human monoclonal anti-DNA antibodies is useful in defining the structural features that give rise to these binding properties. This article systematically reviews the evidence derived from such sequences. Previous reviews of this subject have been hampered by incomplete knowledge of the human immunoglobulin variable region repertoire. In this article, the original sequence data from reports of over 50 human monoclonal antibodies (mAb) are reinterpreted by alignment to the most similar alleles of the most similar germline genes. This allows accurate estimation of the site and nature of somatic mutations. Human IgG monoclonal anti-DNA antibodies generally carry more mutations than IgM. In many cases these have been selected by an antigen-driven process. In many of the more specific, higher affinity dsDNA binders, there is an accumulation of basic residues in the complementarity determining regions. However, many exceptions to this rule exist, particularly among IgM mAb. Unlike murine anti-DNA antibodies, these human mAb show little evidence for preferential use of particular V(H), V(K) and V(lambda) genes or families to encode antibodies of this specificity.


A new regional cotton growth model based on reference crop evapotranspiration for predicting growth processes.
Meteorological conditions and irrigation amounts are key factors that affect crop growth processes. Typically, crop growth and development are modeled as a function of time or growing degree days (GDD). Although the most important component of GDD is temperature, it can vary significantly year to year while also gradually shifting due to climate changes. However, cotton is highly sensitive to various meteorological factors, and reference crop evapotranspiration (ETO) integrates the primary meteorological factors responsible for global dryland extension and aridity changes. This paper constructs a cotton growth model using ETO, which improves the accuracy of crop growth simulation. Two cotton growth models based on the logistic model established using GDD or ETO as independent factors are evaluated in this paper. Additionally, this paper examines mathematical models that relate irrigation amount and irrigation water utilization efficiency (IWUE) to the maximum leaf area index (LAImax) and cotton yield, revealing some key findings. First, the model using cumulative reference crop evapotranspiration (CETO) as the independent variable is more accurate than the one using cumulative growing degree days. To better reflect the effects of meteorological conditions on cotton growth, this paper recommends using CETO as the independent variable to establish cotton growth models. Secondly, the maximum cotton yield is 7171.7 kg/ha when LAImax is 6.043 cm2/cm2, the corresponding required irrigation amount is 518.793 mm, and IWUE is 21.153 kg/(ha·mm). Future studies should consider multiple associated meteorological factors and use ETO crop growth models to simulate and predict crop growth and yield.


The potential of cytotherapeutics in hematologic reconstitution and in the treatment and prophylaxis of graft-versus-host disease. Chapter I: current practice and remaining unmet medical needs.
Hematopoietic stem cell transplantation is a life-saving treatment for inherited anemias, immunodeficiencies or hematologic malignancies. When using partially HLA-matched allografts, a major complication is graft-versus-host disease (GvHD). The ideal attributes of a transformational new GvHD treatment include improved survival, decreased corticosteroids, decreased antifungals, improved quality of life through decreased infections, reduced number of hospital stay days, reduced risks of developing chronic GvHD impact on lower GI tract and liver, prophylactic benefits and decreased GvHD relapses, but, in the case of cancer, without negatively impacting beneficial graft-versus-tumor effects. The current practice of hematopoietic stem cell transplantation, its incidence and its unmet medical needs are reviewed here and discussed.


Investigation of the initial fragmentation of oligodeoxynucleotides in a quadrupole ion trap: charge level-related base loss.
The charge state distribution and CID fragmentation of two series of deprotonated oligodeoxynucleotide (ODN) 9-mers (5'-GGTTXTTGG-3' and 5'-CCAAYAACC-3', X/Y = G, C, A, or T) have been studied in detail in an ion trap in an effort to understand the intrinsic properties of DNA in vacuo. The distribution of charge states (-2 to -6) is similar for both the X- and Y-series, with the most abundant being the -4 charge state. The T-rich X-series prefers higher charge states (-6 and -5) than does the Y-series. Calculations show that phosphate groups located nearest a thymine are more acidic than those near an adenine, cytosine, or guanine, thus explaining why the X-series prefers higher charge states. We use the term "charge level" to define the ratio of the charge state to the total number of phosphate groups present in the ODN. We find, consistent with previous studies, that the initial step of fragmentation is loss of nucleobase either as an anion or as a neutral. We observe the former for ODNs with charge levels greater than 50% and the latter for ODNs with charge levels below 50%. The overall anionic base loss follows the trend A(-) >> G(-) approximately T(-) > C(-); electrostatic potential calculations indicate that this trend follows delocalization of electron density for each anion, with A(-) being the most stabilized through delocalization. For neutral base loss, thymine (TH) is rarely cleaved, while the preferences for AH, GH, and CH loss vary. Proton affinity (PA) calculations show that a nearby negatively charged phosphate enhances the PA of proximally located nucleobases; this PA enhancement probably plays a role in promoting neutral base loss. The trends differ by charge level. At a charge level of 37.5% (-3 charge state), AH loss is preferred over CH and GH loss, regardless of sequence. However, at a charge level of 25% (-2 charge state), the terminal bases are preferentially lost over the internal bases, regardless of identity. By reconstructing the ODN sequences from structurally informative (a-BH) and w ions, we are able to identify the charge locations for the -3 and -2 charge states. For the -3 charge state, one charge resides on each "most terminal" phosphate, with the third being in the middle. For the -2 charge state, each charge resides on the penultimate phosphate groups. We compare our data to earlier experiments in an effort to generalize trends.


Hemodynamic effects of molsidomine at rest and during submaximal and maximal exercise in patients with coronary artery disease limited by exertional angina pectoris.
To analyze the mechanisms of action of molsidomine, a new antianginal drug, 10 patients with coronary artery disease and exertional angina pectoris were studied. Hemodynamic measurements were made at rest, during submaximal exercise and during angina-limited exercise before and 1 hour after intravenous administration of 2 mg of molsidomine. When angina pectoris was prevented after the drug was given (6 of 10 patients), the exercise intensity was increased until the recurrence of angina (3 patients) or until exhaustion (3 patients), and hemodynamic data were recorded at this higher exercise capacity. At rest and during submaximal exercise, molsidomine increased heart rate and decreased cardiac output and mean systemic and pulmonary arterial pressures. The prevention of angina pectoris was attended by lower mean systemic and pulmonary arterial pressures and pressure-rate product; cardiac output and heart rate were unchanged. The greater exercise capacity (+26 percent) after molsidomine was attended by increases in maximal cardiac output (+19 percent) and in arteriovenous oxygen difference (+6 percent); the maximal pressure-rate product was unchanged and systemic vascular resistance was lower. The mechanisms of action of molsidomine are very similar to those of nitrates and imply a decrease in venous and arterial tone. Molsidomine deserves further study in patients with angina or congestive heart failure.


Retinal dystrophy in Wistar-Furth rats.
A form of retinal degeneration in the Wistar-Furth strain of rat is described. The changes observed was classified as either mild or severe, depending on the severity of the dystrophy seen by light and electron microscopy. In the mild stage, there was a slight decrease in the number of photoreceptor nuclei in the outer nuclear layer (ONL) and there were pyknotic nuclei in the inner nuclear layer. A few photoreceptor outer and inner segments showed focal swellings. The basal infoldings of the retinal pigment epithelium (RPE) were distributed irregularly, creating spaces that contained collagen-like fibrils. However, the interepithelial tight junctions remained impermeable to intravenously injected peroxidase. In severely dystrophic retinas, there was a further decrease in the width of the ONL, and the photoreceptor outer and inner segments were degenerated. In extreme cases, the photoreceptor cell disappeared completely and the inner retina abutted the RPE. Further changes were also noted in the basal membrane of the RPE; in some regions the membrane was totally flat while in others it formed exaggerated infoldings. In addition, the RPE was frequently vascularized by vessels that originated from the retina. The endothelium of those intra-RPE vessels located near Bruch's membrane was frequently fenestrated. Alterations also occurred in the retinal capillaries; some were degenerated, while others showed increased tortuosity or focal thickenings of the basal lamina. In addition, there were focal increases in the amount of stroma between Bruch's membrane and the choriocapillaris.


A novel regional-scale human health risk assessment model for soil heavy metal(loid) pollution based on empirical Bayesian kriging.
Soil heavy metal(loid)s contamination caused by rapid urbanization and industrialization seriously affects human health and hinders the global sustainable development goals (SDGs). Currently, there is a lack of comprehensive human health risk assessment (HHRA) studies for multiple land use types at the regional scale. We propose a practical risk assessment framework that integrates empirical Bayesian kriging (EBK), pollution level analyses, and modified HHRA modeling. The concentrations of copper industry-related metals (Cu, Ni, Cd, As, and Hg) in 332 topsoil samples from the south bank of the Yangtze River in Tongling were investigated. Obvious enrichment of Cu, Cd, As, and Hg was detected, and the average concentration of Cu was 5.24 times higher than the background values. The distribution of heavy metal(loid) pollution was typically high in the south and east, and low in the north and west. The mean errors of interpolation for Cu, Ni, and Hg were 0.84, 1.29, and 0, respectively, and the root mean square errors of interpolation for Cd and As were 1.29 and 0.86, respectively. Non-carcinogenic risks of soil heavy metal(loid)s were assessed as acceptable throughout the studied area. The hazard index decreased in the order As (0.448) > Ni (0.0729) > Cd (0.0136) > Hg (9.04 ×10-4) > Cu (6.41 ×10-4). Nevertheless, the carcinogenic risks of Ni, Cd, and As in 70-80% of the administrative units (AUs) were between 10-6 to 10-4, considered an unacceptable level. Exposure through the oral ingestion route accounted for 88.0-99.2% of the total three exposure routes. It is worth noting that four AUs were considered to be the priority control units, and Ni and As were identified as the priority control soil heavy metal(loid)s. This case demonstrates the feasibility and scientific validity of the new EBK-HHRA framework, which confirms that EBK can effectively predict the spatial distribution patterns of soil heavy metal(loid)s and that modified HHRA models are conducive to risk integration at the regional scale. The EBK-HHRA approach is generic and provides substantial support for risk source identification and risk management of soil heavy metal(loid)s contamination at the regional scale.


The distribution of endogenous chicken retrovirus sequences in the DNA of galliform birds does not coincide with avian phylogenetic relationships.
The chicken is a domesticated form of Red Jungle-fowl (Gallus gallus), which belongs to the Pheasant family (Phasianidae) within the order Galliformes. Domestic chickens carry the genome of the endogenous retrovirus RAV-O as DNA sequences integrated into host chromosomes transmitted through the germ line. We have examined the presence and distribution of RAV-O-related sequences in the DNA of Red Junglefowl and other closely related species of Junglefowl, as well as more distantly related Pheasants and Quail. DNA sequences homologous to RAV-O were analyzed by molecular hybridization in liquid and after electrophoresis of restriction endonuclease fragments. The presence of RAV-O-related sequences in avian DNA does not correlate with phylogenetic relationships. Under stringent conditions of hybridization in liquid, DNA sequences homologous to RAV-O cDNA were detected at high levels (greater than 80% homology( only in the genomes of the domestic chicken and its phylogenetic ancestor, the Red Junglefowl (Gallus gallus). The DNA of two other species of Gallus (G. sonnerati, Sonnerat's Junglefowl and G. varius, Green Junglefowl), of Ring-necked Pheasant and of Japanese Quail contained sequences with less than 10% homology to RAV-O cDNA. Under conditions permitting mismatching, however, Ring-necked Pheasant DNA hybridized up to 50% of the RAV-O cDNA, and Quail DNA 24%, whereas the extent of hybridization to Sonnerat's and Green Junglefowl DNA was not markedly increased. Analysis of restriction enzyme digests revealed several distinct fragments of DNA hybridizing to chick retrovirus cDNA in both Red Junglefowl and domestic chicken, and multiple fragments in DNA from two species of Phasianus. No fragments with sequences related to chicken retroviruses were found, however, in digests of DNA prepared from Sonnerat's, Ceylonese and Green Junglefowl, from two other Pheasant genera (Chrysolophus and Lophura), or from one Quail genus (Coturnix). Thus the DNA of three Junglefowl species closely related to Gallus gallus lacked RAV-O sequences while the DNA of more distantly related Phasianus species showed significant homology. These results show that RAV-O-related sequences have not diverged together with the normal host genes during the evolution of the Phasianidae. Although RAV-O sequences are endogenous in all domestic chickens and Red Junglefowl studied thus far, it appears that the RAV-O genome has been introduced relatively recently into the germ line of Gallus gallus, following speciation but before domestication, and independently of the related sequences found in members of the genus Phasianus.


Sexuality after sigmoid vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser syndrome.
To investigate the functional and sexual outcome of sigmoid vaginoplasty in patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Prospective study. University hospital. Fifty-nine consecutive patients with MRKH syndrome. Forty-eight patients underwent sigmoid vaginoplasty, and 11 were treated using the Frank method of dilatation. Functional results and sexuality were evaluated with the use of two standardized questionnaires: the Female Sexual Function Index (FSFI) and the revised Female Sexual Distress Scale (FSDS-R). Questions were added to analyze depression, body image perception, and desire of motherhood. Out of the 68% of patients who answered the questionnaire, 73% had regular sexual intercourse. The mean total FSFI score was 28 ± 3.1 in the operated group and 30 ± 5.3 in the group treated with the Frank method. Their mean FSDS-R scores were 21 ± 12.1 and 18 ± 13.8, respectively. Sigmoid vaginoplasty is an effective technique providing a nearly normal sexual function to patients with vaginal aplasia. Despite this, psychologic distress related to sexuality persists in most patients, demonstrating the need for a multidisciplinary support.


Does time of surgery and complication have any correlation in the management of hip fracture in elderly and can early surgery affect the outcome?
Hip fractures in the elderly are usually associated with a high rate of morbidity and mortality and affect quality of life. On review of published data, the current guidelines in the literature indicate that early surgery should be performed within 24 h of injury because it is associated with better functional outcomes and lower rates of perioperative complications and mortality. The aim of this study was to evaluate whether any correlation exists between early surgical intervention and functional outcomes. In a retrospective study, we analyzed the records between January 2010 and December 2016 and 550 elderly patients between the age group of 65-95 were included. The results of early surgery were promising, 451 (82%) patients did not have any complication, 42 (7.6%) has developed bed sore, 23 (4%) developed a hospital-acquired infection, 13 (2.3%) developed wound infection, 08 (1.4%) developed DVT, 04 (0.7%) developed implant failure, and 09 (01%) died of some or other complications. Still, there is conflicting evidence in the published data that early surgery would improve mortality and function. However, early surgery definitively improves outcome and reduces morbidity, bed sores, infection, and the length of hospital stay could be improved by reducing the waiting time of hip surgery following fracture. We concluded that it is beneficial to the elderly patients to receive surgical treatment as early as possible.


Interleukin-6 receptor blockade or TNFα inhibition for reducing glycaemia in patients with RA and diabetes: post hoc analyses of three randomised, controlled trials.
Diabetes is common in patients with rheumatoid arthritis (RA). Interleukin (IL)-6 is implicated in both the pathogenesis of RA and in glucose homeostasis; this post hoc analysis investigated the effects of IL-6 receptor vs. tumour necrosis factor inhibition on glycosylated haemoglobin (HbA1c) in patients with RA with or without diabetes. Data were from two placebo-controlled phase III studies of subcutaneous sarilumab 150/200 mg q2w + methotrexate or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and a phase III monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w. Patients with diabetes were identified by medical history or use of antidiabetic medication (patients with HbA1c ≥ 9% were excluded from all three studies). HbA1c was measured at baseline and weeks 12/24. Safety and efficacy were assessed in RA patients with or without diabetes. Patients with diabetes (n = 184) were older, weighed more and exhibited higher RA disease activity than patients without diabetes (n = 1928). Regardless of diabetes status, in patients on background csDMARDs, least squares (LS) mean difference (95% CI) in change from baseline in HbA1c for sarilumab 150 mg/200 mg vs. placebo at week 24 was - 0.28 (- 0.40, - 0.16; nominal p < 0.0001) and - 0.42 (- 0.54, - 0.31; nominal p < 0.0001), respectively. Without csDMARDs, LS mean difference for sarilumab 200 mg vs. adalimumab 40 mg at week 24 was - 0.13 (- 0.22, - 0.04; nominal p = 0.0043). Greater reduction in HbA1c than placebo or adalimumab was observed at week 24 with sarilumab in patients with diabetes and/or baseline HbA1c ≥ 7%. There was no correlation between baseline/change from baseline in HbA1c and baseline/change from baseline in C-reactive protein, 28-joint Disease Activity Score, or haemoglobin, nor between HbA1c change from baseline and baseline glucocorticoid use. Medical history of diabetes or use of diabetes treatments had limited impact on safety and efficacy of sarilumab and was consistent with overall phase III findings in patients with RA. In post hoc analyses, sarilumab was associated with a greater reduction in HbA1c than csDMARDs or adalimumab, independent of sarilumab anti-inflammatory effects. Prospective studies are required to further assess these preliminary findings. ClinTrials.gov NCT01061736: date of registration February 03, 2010; ClinTrials.gov NCT01709578: date of registration October 18, 2012; ClinTrials.gov NCT02332590: date of registration January 07, 2015.


Endovascular reconstruction by means of stent placement in symptomatic intracranial atherosclerotic stenosis.
Patients with intracranial atherosclerosis who fail antithrombotic therapy have a poor prognosis. The high rate of recurrent stroke warrants testing alternative treatments such as intracranial angioplasty. We present our experience in the treatment of 104 patients (age range, 54-82 years; mean age, 67 years) with symptomatic intracranial atherosclerotic stenoses despite medical therapy who underwent stent-assisted angioplasty. Patient records were retrospectively analysed for location and degree of stenosis, regimen of antiplatelet agents, devices used, procedure-related complications and adverse events. Clinical (Modified Rankin Scale) and radiographic outcomes were obtained 24 hours, 1 month and 3-6 months after treatment. Sixty-five lesions (62.5%) were located in the posterior circulation. Mean stenosis was 75.4%. In all patients, the angiographic degree of stenosis was reduced to less than 30%. One stent was implanted in 66 patients (63%), and two or more in 38 patients (37%). Modified Rankin Scale (mR) was 1-2 in 67.5% of the cases, 3-4 in 25.9%, 5 in 2.8%, 6 in 3.8%. Procedural morbidity was 5.7% and procedural mortality was 3.8%. Angiographic follow-up was available in 58 patients (55.7%) and the restenosis rate was 12.5%. In selected patients, endovascular revascularization of intracranial arteries by means of stent-assisted angioplasty is technically feasible, effective and safe.


A fusion of CD63-BCAR4 identified in lung adenocarcinoma promotes tumorigenicity and metastasis.
Recently, fusion variants of the breast cancer anti-oestrogen-resistance 4 (BCAR4) gene were recurrently discovered in lung adenocarcinoma from the genome-wide studies. However, the functional characterisation of BCAR4 fusion has not been investigated. Based on the analysis of RNA-sequencing data, we identified a fusion transcript of CD63-BCAR4 in a Korean patient with lung adenocarcinoma who did not harbour any known activating mutations in EGFR and KRAS genes. To investigate the oncogenic effect of CD63-BCAR4, in vitro and in vivo animal experiments were performed. In vitro experiments showed strongly enhanced cell migration and proliferation by the exogenous expression of CD63-BCAR4 protein in bronchial epithelial cells. Cell migration was notably reduced after knockdown of BCAR4 fusion by small-interfering RNA. The tumorigenic and metastatic capability of the CD63-BCAR4 fusion was confirmed by using the mouse xenograft model. Fusion-overexpressed cells result in metastasis to the liver and lung as well as the primary tumours after subcutaneous injection into mice. Cyclin D1, MMP1, Slug and mesenchymal markers were significantly increased after CD63-BCAR4 overexpression in the in vitro and in vivo experiments. Taken together, our results suggest a newly identified fusion gene, CD63-BCAR4 as a potential novel oncogene in lung adenocarcinoma.


Simultaneous determination of tryptophan and its 5-hydroxy metabolites in human cerebrospinal fluid by reversed phase liquid chromatography with electrochemical detection.
A sensitive ion-pair reversed phase liquid chromatographic method for determining tryptophan, 5-hydroxytryptophan, 5-hydroxytryptamine (serotonin) and 5-hydroxyindole acetic acid has been developed. To separate these indoles in cerebrospinal fluid both octadecyl- and phenyl-bonded columns were tested. The effect of an ion-pair reagent (n-heptyl sulphonate) and pH of the mobile phase on the separation was examined. With the method described the concentrations of the four indoles can be determined within 45 min without sample pretreatment. The sensitivity obtained with electrochemical detection is 0.45 mumol/l for tryptophan and 2-4 nmol/l for 5-hydroxyindoles in human cerebrospinal fluid samples.


Long-term follow-up after eradication of Helicobacter pylori with omeprazole, clarithromycin, and tinidazole (OCT regimen) in a Japanese population.
The long-term benefit of Helicobacter pylori eradication treatment that includes metronidazole on peptic ulcer disease in Japan is unclear. We investigated the rate of H. pylori re-infection and ulcer relapse after H. pylori eradication. A total of 266 patients with endoscopically confirmed peptic ulcer disease and H. pylori infection were treated with triple therapy of omeprazole 40 mg (20 mg b.i.d.), clarithromycin 800 mg (400 mg b.i.d.), and tinidazole 1000 mg (500 mg b.i.d.) for 7 days. Endoscopy with gastric biopsy was performed before and 1 month, 6 months, 1.5 years, and 3.5 years after therapy. H. pylori status was determined by H. pylori culture, rapid urease test, and histopathology. 13C-urea breath test was done at 6 months after eradication therapy. Treatment was deemed successful when all tests were negative at 6 months after therapy by endoscopic biopsy. Successful H. pylori eradication was achieved in 262/266 (98.5%) patients with peptic ulcer. Total relapse of peptic ulcer occurred in 8/262 (3%) patients after eradication, with 3/262 (1.1%) occurring within 1.5 years after treatment and 5/262 (1.9%) within 3.5 years. All relapsed patients were found to be H. pylori-positive at the time of relapse. Of the 262 patients who experienced eradication, 20 (7.6%) were subsequently re-infected, six (2.3%) within 1.5 years and 14 (5.3%) within 3.5 years. Triple therapy with omeprazole, clarithromycin, and tinidazole (OCT) is useful for H. pylori eradication in Japan, but there is an appreciable re-infection rate in this population.