The chemokine SDF-1alpha suppresses fibronectin-mediated in vitro lymphocytes adhesion.
Stromal cell-derived factor (SDF-1) is a CXC chemokine that selectively activates the CXCR4 chemokine receptor. Fibronectin is an intracellular matrix component that binds integrin and mediates cell-matrix adhesion. Activation of the integrin receptor can occur in two ways: by ligand binding (outside-in signaling), and in response to intracellular events (inside-out signaling). In the current study we showed that SDF-1a inhibited adhesion of T lymphocyte Jurkat cells resulting from binding high concentrations of fibronectin as well as that of THP-1 monocytes. The effect of SDF-1a on fibronectin-mediated adhesion was partly reversed by the CXCR4 receptor antagonist T140. Our results suggest that an SDF-1/ CXCR4 signal pathway modulates fibronectin-mediated lymphocytes adhesion.


Effect of early interventions with manual lymphatic drainage and rehabilitation exercise on morbidity and lymphedema in patients with oral cavity cancer.
There are clinical and statistical inconsistencies regarding early intervention with manual lymphatic drainage (MLD). The purpose of this study was to compare the short-term effect of early interventions with rehabilitation exercise versus MLD and rehabilitation exercise in terms of pain, range of motion (ROM) and lymphedema in patients with oral cancer after surgery. A total of 39 patients who underwent surgery from December 2014 to December 2018 participated in this randomized single-blind study. There were 20 patients in the rehabilitation (R) group and 19 in the MLD (M) plus rehabilitation group. The R group received 30 minutes of rehabilitation intervention; and the M group received 30 minutes of MLD, in addition to 30 minutes of rehabilitation intervention in a work day. Clinical measures, including the visual analog pain scale (VAS), ROM of the neck and shoulder, ultrasonography and face distance for lymphedema, and the Földi and Miller lymphedema scales, were assessed before surgery, before intervention and when discharged from the hospital. The VAS pain score, ROM of the neck, and internal and external rotation of the right shoulder were significantly improved after the interventions. Right-face distance (P = .005), and skin-to-bone distance (SBD) of the bilateral horizontal mandible and left ascending mandibular ramus were significantly improved after the interventions. Left lateral flexion of the neck (P = .038) and SBD of the right ascending mandibular ramus (P < .001) in the MLD group showed more improvement than that of the rehabilitation group. Early intervention with MLD and the rehabilitation program were effective in improving ROM of the neck and controlling lymphedema in acute-phase rehabilitation. The preliminary findings suggest a potential therapeutic role for early intervention with MLD, in addition to rehabilitation exercise, in that they yielded more benefits in lymphedema control and improvement of ROM of the neck in acute care.


Biological Effects of Clinically Relevant CoCr Nanoparticles in the Dura Mater: An Organ Culture Study.
Medical interventions for the treatment of spinal disc degeneration include total disc replacement and fusion devices. There are, however, concerns regarding the generation of wear particles by these devices, the majority of which are in the nanometre sized range with the potential to cause adverse biological effects in the surrounding tissues. The aims of this study were to develop an organ culture model of the porcine dura mater and to investigate the biological effects of CoCr nanoparticles in this model. A range of histological techniques were used to analyse the structure of the tissue in the organ culture. The biological effects of the CoCr wear particles and the subsequent structural changes were assessed using tissue viability assays, cytokine assays, histology, immunohistochemistry, and TEM imaging. The physiological structure of the dura mater remained unchanged during the seven days of in vitro culture. There was no significant loss of cell viability. After exposure of the organ culture to CoCr nanoparticles, there was significant loosening of the epithelial layer, as well as the underlying collagen matrix. TEM imaging confirmed these structural alterations. These structural alterations were attributed to the production of MMP-1, -3, -9, -13, and TIMP-1. ELISA analysis revealed that there was significant release of cytokines including IL-8, IL-6, TNF-α, ECP and also the matrix protein, tenascin-C. This study suggested that CoCr nanoparticles did not cause cytotoxicity in the dura mater but they caused significant alterations to its structural integrity that could lead to significant secondary effects due to nanoparticle penetration, such as inflammation to the local neural tissue.


Sequence variability in two mitochondrial DNA regions and internal transcribed spacer among three cestodes infecting animals and humans from China.
Sequence variability in two mitochondrial DNA (mtDNA) regions, namely cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 4 (nad4), and internal transcribed spacer (ITS) of rDNA among and within three cestodes, Spirometra erinaceieuropaei, Taenia multiceps and Taenia hydatigena, from different geographical origins in China was examined. A portion of the cox1 (pcox1), nad4 genes (pnad4) and the ITS (ITS1+5.8S rDNA+ITS2) were amplified separately from individual cestodes by polymerase chain reaction (PCR). Representative amplicons were subjected to sequencing in order to estimate sequence variability. While the intra-specific sequence variations within each of the tapeworm species were 0-0.7% for pcox1, 0-1.7% for pnad4 and 0.1-3.6% for ITS, the inter-specific sequence differences were significantly higher, being 12.1-17.6%, 18.7-26.2% and 31-75.5% for pcox1, pnad4 and ITS, respectively. Phylogenetic analyses based on the pcox1 sequence data revealed that T. multiceps and T. hydatigena were more closely related to the other members of the Taenia genus, and S. erinaceieuropaei was more closely related to the other members of the Spirometra genus. These findings demonstrated clearly the usefulness of mtDNA and rDNA sequences for population genetic studies of these cestodes of socio-economic importance.


Effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells.
Cryopreservation is widely used in regenerative medicine for tissue preservation. In the present study, the effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells (HUVECs) were investigated. After 0, 4, 8, 12 or 24 weeks of cryopreservation in liquid nitrogen, the HUVECs were thawed. The excretory functions markers (endothelin‑1, prostaglandin E1, von Willebrand factor and nitric oxide) of HUVECs were measured by ELISA assay. The expression of intercellular adhesion molecule‑1 (ICAM‑1) in HUVECs was analyzed using flow cytometry. An angiogenesis assay was used to determine the angiogeneic capabilities of the thawed HUVECs. The results demonstrated that cryopreserved/thawed and recultivated HUVECs were unsuitable for tissue‑engineered microvascular construction. Specifically, the excretory function of the cells was significantly decreased in the post‑cryopreserved HUVECs at 24 weeks. In addition, the level of ICAM‑1 in HUVECs was significantly upregulated from the fourth week of cryopreservation. Furthermore, the tube‑like structure‑forming potential was weakened with increasing cryopreservation duration, and the numbers of lumen and the length of the pipeline were decreased in the thawed HUVECs, in a time‑dependent manner. In conclusion, the results of the present study revealed that prolonged cryopreservation may lead to HUVEC dysfunction and did not create stable cell lines for tissue‑engineered microvascular construction.


Cloning and characterization of an Ito-like potassium channel from ferret ventricle.
FK1, a ferret ventricular full-length cDNA clone, encodes a 654-amino acid protein with 98% identity to human K+ transient outward current (Ito)-like HK1 (Tamkun et al. FASEB J.5: 331-337, 1991). FK1 is detectable in ferret brain, atrium, left and right ventricle, and kidney but not in skeletal muscle, endothelial cells, aorta, and liver. In Xenopus oocytes, FK1 cRNA gives rise to a rapidly activating and inactivating Ito-like current, which is highly K+ selective (Na(+)-to-K+ permeability ratio = 0.003). Activation occurs over an approximately 50-mV range (-40 to +10 mV) and displays a sigmoid delay in onset with potential-dependent time constants that decrease with depolarization. Steady-state activation can be described with either a simple Boltzmann relationship [half-activation potential (V1/2) = -25 mV, slope (k) = 10 mV] or a Boltzmann relationship raised to either the third or fourth power (alpha 3: V1/2 = -43 mV, kappa = 13.1 mV; alpha 4: V1/2 = -48 mV, kappa = 13.6 mV, where alpha is the activation variable). Inactivation kinetics are biexponential, with the main fast time constant becoming independent of membrane potential depolarized to 0 mV. Steady-state inactivation can be described with a single Boltzmann relationship (V1/2 = -57 mV, kappa = 5.0 mV). Fast inactivation is removed by NH2-terminal deletions. Recovery from inactivation (-90 mV) is quite slow (half-time = 4.8 +/- 2.5 s). In 2 mM extracellular K+ concentration ([K+]o), FK1 tail currents display conventional deactivation behavior; however, in 98 mM [K+]o the tail currents display "reopening" behavior. These results suggest a molecular basis for the electrophysiological similarities between ferret and human ventricular Ito (Campbell et al. J. Gen. Physiol. 101: 571-601, 1993; Näbauer et al. Circ. Res. 73: 386-394, 1993).


Clinical, ultrasonographic and histological findings in varicose vein surgery.
This study aims to correlate the demographic data, different clinical degrees of chronic venous insufficiency (CEAP), ultrasound findings of saphenofemoral junction (SFJ) reflux, and anatomopathological findings of the proximal segment of the great saphenous vein (GSV) extracted from patients with primary chronic venous insufficiency (CVI) submitted to stripping of the great saphenous vein for the treatment of lower limb varicose. This is a prospective study of 84 patients (110 limbs) who were submitted to the stripping of the great saphenous vein for the treatment of varicose veins of the lower limbs, who were evaluated for CEAP clinical classification, the presence of reflux at the SFJ with Doppler ultrasonography, and histopathological changes. We study the relationship between the histopathological findings of the proximal GSV withdrawal of patients with CVI with a normal GSV control group from cadavers. The mean age of the patients was higher in the advanced CEAPS categories when comparing C2 (46,1 years) with C4 (55,7 years) and C5-6(66 years), as well as C3 patients (50,6 years) with C5-6 patients. The normal GSV wall thickness (mean 839,7 micrometers) was significantly lower than in the saphenous varicose vein (mean 1609,7 micrometers). The correlational analysis of reflux in SFJ with clinical classification or histopathological finding did not show statistically significant findings. The greater the age, the greater the clinical severity of the patients. The GSV wall is thicker in patients with lower limb varicose veins, but those histopathological changes are not correlated with the disease's clinical severity or reflux in the SFJ on a Doppler ultrasound.


Six hundred fifty-six consecutive explorations for primary hyperparathyroidism.
To review the outcomes of 656 consecutive parathyroid explorations performed by a single surgeon and to compare the results of conventional and minimally invasive parathyroidectomy (MIP) techniques. Traditional surgery for primary hyperparathyroidism (HPTH) involves bilateral cervical exploration, which is usually accomplished under general endotracheal anesthesia. The MIP technique involves preoperative localization with sestamibi scans, surgeon-administered cervical block anesthesia, directed exploration through a small incision, intraoperative rapid parathyroid hormone assay, and discharge within 2 to 3 hours of surgery. Six hundred fifty-six consecutive patients with primary HPTH underwent exploration between January 1990 and March 2001. MIP was used with ever-increasing frequency beginning in March 1998. Four hundred one procedures (61%) were performed using the standard technique and 255 patients (39%) were selected for MIP. The success rate for the entire series was 98%, with no significant differences comparing traditional and MIP techniques. The overall complication rate of 2.3% reflects 3.0% and 1.2% rates in the standard and MIP groups, respectively. MIP was associated with approximately a 50% reduction in operating time, a sevenfold reduction in length of hospital stay, and a mean cost savings of $2,693 per procedure, which represents nearly a 50% reduction in total hospital charges. A dramatic and sustained shift has occurred in the surgical treatment of primary HPTH: MIP has replaced traditional exploration for most patients.


Section of the abductor hallucis tendon for correction of metatarsus varus deformity.
Section of the abductor hallucis tendon is recommended for early correction of the metatarsus adductus deformity especially in the residual of a treated equinovarus foot. The operation is simple and safe, with very little postoperative morbidity. The effectiveness of the procedure is enhanced if a tight abductor hallucis tendon is demonstrated. The operation may also be helpful in conjunction with other surgical procedures for correction of the varus deformity of a clubfoot.


Acute interruption of treatment with nandrolone decanoate is not sufficient to reverse cardiac autonomic dysfunction and ventricular repolarization disturbances in rats.
Anabolic androgenic steroids are a class of synthetic compounds derived from testosterone, eventually used by athletes, to improve physical performance. However, anabolic steroids can also modify normal cardiovascular function. Thus, we investigated cardiac electrophysiological and autonomic abnormalities in rats, through a electrocardiographic variability protocol during and after interruption of administration of nandrolone decanoate (DECA) anabolic steroid. Twenty male Wistar rats (60-70 days old) received DECA (10 mg. kg-1i.m) once a week or vehicle, during eight weeks. Electrocardiogram was recorded in conscious rats by a noninvasive method, and time and domain analysis of heart rate variability as well as electrocardiogram intervals (QTc / QTd) were performed. Body mass was lower in treated rats compared to control after 4th and 8th weeks, but not at the end of 14th week. QTc and QTd were longer in DECA group compared to control on 4th, 8th, 11th, but equal on 14th week. Cardiac autonomic dysfunction (vagal attenuation) was present on DECA group after 4th week and did not normalize after interruption of treatment. The animals of DECA group showed a correlation between attenuated parasympathetic modulation and increased correct QT interval. Our data allow us to conclude that long-term treatment with DECA impairs autonomic cardiac physiology, predisposing to cardiovascular risk and sudden death, and interruption of administration does not recovery the normality immediately.


Sleep stage determines the expression pattern of sleep apneas.
We report on an obese man with sleep stage-dependent apnea. His type of apnea was predominantly central during non-rapid eye movement (NREM) sleep, while it was obstructive during rapid eye movement (REM) sleep. We found significantly more and more severe apneas during REM sleep compared to NREM sleep. His apneas were remarkably reduced by position adjustment, suggesting that upper airway collapse played a key role in the induction of both types of apnea. As his apneic patterns were dependent on the sleep stages, we assumed that the balance between upper airway obstruction and instability of central respiratory control might be important in determining the expression types.


Dealing with fear of blushing: a psychoeducational group intervention for fear of blushing.
The clinical impression is that people who fear blushing do not easily seek psychological help for their complaints. Therefore, we designed a low-threshold psychoeducational group intervention to reduce fear of blushing. The intervention followed a cognitive-behavioural approach, but in a course setting, e.g., with 'participants' and 'teachers' instead of 'patients' and 'therapists'. The effectiveness of the course in reducing fear of blushing and social anxiety was tested in a group of blushing-fearful individuals (n = 47) by using an uncontrolled study design. The course consisted of six weekly sessions and one booster session 3 months after the last regular session. Assessments took place upon application, immediately before the intervention, after the sixth session, before the booster session, and at 1-year follow-up. Results showed that the course was effective in reducing fear of blushing as well as symptoms of social anxiety. The positive effect of the course on anxiety measures suggests that it might be a promising approach for treating fear of blushing. The course 'dealing with fear of blushing' is a cognitive-behavioural group intervention in a course setting, e.g., with 'participants' and 'teachers' instead of 'patients' and 'therapists'. The course was effective in reducing anxiety complaints. An effect size of 1.4 and a reduction of approximately 30 points on this Blushing, Trembling and Sweating Questionnaire are comparable with what was reported for individual cognitive-behavioural treatments. Participants evaluated the course positively.


CHROMOSOMAL VERSUS MITOCHONDRIAL DNA EVOLUTION: TRACKING THE EVOLUTIONARY HISTORY OF THE SOUTHWESTERN EUROPEAN POPULATIONS OF THE SOREX ARANEUS GROUP (MAMMALIA, INSECTIVORA).
The shrews of the Sorex araneus group have undergone a spectacular chromosome evolution. The karyotype of Sorex granarius is generally considered ancestral to those of Sorex coronatus and S. araneus. However, a sequence of 777 base pairs of the cytochrome b gene of the mitochondrial DNA (mtDNA) produces a quite different picture: S. granarius is closely related to the populations of S. araneus from the Pyrenees and from the northwestern Alps, whereas S. coronatus and S. araneus from Italy and the southern Alps represent two well-separated lineages. It is suggested that mtDNA and chromosomal evolution are in this case largely independant processes. Whereas mtDNA haplotypes are closely linked to the geographical history of the populations, chromosomal mutations were probably transmitted from one population to another. Available data suggest that the impressive chromosome polymorphism of this group is quite a recent phenomenon.


An analogue peptide from the Cancer/Testis antigen PASD1 induces CD8+ T cell responses against naturally processed peptide.
We have previously identified the novel Cancer/Testis antigen PASD1 by immunoscreening a testis library with pooled acute myeloid leukemia (AML) patient sera. To develop a cytotoxic T lymphocyte (CTL)-inducing vaccine, we have now investigated the carboxy-terminal region, known to contain serological determinants, for MHC class I (HLA-A⋆0201)-binding peptides. Algorithm-selected natural peptides failed to show detectable HLA-A⋆0201 binding in T2 assays. However, anchor-modified analogue peptides showed enhanced binding, with decreased off-rates. Analogue peptide-loaded antigen-presenting cells (APCs) induced IFN-γ production by T cells from normal donors and patients. In addition, peptide-specific T cells could be expanded from cancer patients by stimulation with the PASD1 analogue peptide Pa14. For clinical application, a DNA fusion gene vaccine encoding Pa14 was designed and tested in "humanized" mice. Splenocytes from vaccinated mice showed in vitro cytotoxicity against tumour cells, either exogenously loaded with the corresponding wild-type peptide (Pw8) or expressing endogenously processed PASD1 protein. We show for the first time that a DNA vaccine encoding an altered PASD1 epitope can induce CTLs to target the natural peptide expressed by human tumour cells.


Multiparametric Magnetic Resonance Imaging in the Diagnosis of Clinically Significant Prostate Cancer: an Updated Systematic Review.
There has been growing utilisation of multiparametric magnetic resonance imaging (MPMRI) as a non-invasive tool to diagnose and localise clinically significant prostate cancer (CSPCa). This updated systematic review examines the use of MPMRI in patients with an elevated risk of CSPCa who have had a prior negative transrectal ultrasound systematic biopsy (TRUS-SB) and who were biopsy naïve. MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews were searched for existing systematic reviews published up to September 2020. The literature search of the electronic databases combined disease-specific terms (prostate cancer, prostate carcinoma, etc.) and treatment-specific terms (magnetic resonance, etc.). Studies were included if they were randomised controlled trials (RCTs) comparing MPMRI to template transperineal mapping biopsy (TPMB) or to TRUS-SB. Thirty-six RCTs were eligible. For biopsy-naïve men, accuracy of diagnosis of CSPCa showed sensitivities from 87 to 96% and specificities ranging from 29 to 45%. Meta-analyses for CSPCa showed increased detection favouring MPMRI-targeted biopsy over TRUS-SB by 3% (95% confidence interval 0-7%, P = 0.03) and decreased detection of clinically insignificant prostate cancer (CISPCa) favouring MPMRI by 8% (95% confidence interval -11 to 5%, P < 0.00001). Accuracy of MPMRI for men with prior negative biopsy showed sensitivities of 78-100% and specificities of 30-100%. Meta-analyses comparing MPMRI to TRUS-SB showed increased detection of 5% (95% confidence interval 3-7%, P < 0.0001) with a reduction of CISPCa detection of 7% (95% confidence interval 4-9%, P < 0.00001). The growing acceptance of MPMRI utilisation internationally and the recent publication of several RCTs regarding MPMRI in reducing CISPCa detection rates, particularly in biopsy-naïve men, without loss of sensitivity for CSPCa necessitates the synthesis of updated evidence examining MPMRI in the diagnosis of CSPCa.


Prognostic significance of the nuclear DNA content in localized prostatic adenocarcinoma.
The objective of this study was to determine if the nuclear DNA content could predict disease progression in patients with stage A or B prostatic cancer. The nuclear DNA content was determined by image analysis using Feulgen-stained nuclei in tissue sections of prostatic needle biopsies from 44 patients. The patients were followed for a mean of 69.5 months, during which 12 (17%) progressed to stage D2 disease (bone or soft tissue metastases). The average times to progression to stage D2 disease were 68 months for patients who initially had stage A2 disease, 47 months for stage B1 patients and 29 months for stage B2 patients. The DNA pattern was judged diploid or normal-range (Auer type I or II histogram) in 35 tumors (80%) and aneuploid (Auer type III or IV histogram) in 9 tumors (20%). Eight (89%) of 9 tumors with an aneuploid DNA pattern and 4 (11%) of 35 tumors with a normal-range or diploid DNA pattern progressed to stage D2 disease.


Titanium implants and lateral forces. An experimental study with sheep.
The purpose of this study was to investigate the resistance of titanium implants to horizontal forces in a sheep model. Twenty implants were inserted into the foreheads of 5 sheep, 4 implants on each animal. After a healing period of 3 months, abutments were mounted on the implants. After a further healing period of 3 weeks, the implants were loaded with a horizontal pull of orthodontic elastics. The force varied between 250 and 350 grams. The duration of loading was 3 months. After the loading period the animals were sacrificed and the forehead bones with implants were fixed in formalin and evaluated histologically. In the histological specimens no signs of infection or bone loss were found around the implants. The results of the present study encourage the use of titanium implants also in cases where constant lateral forces are present.


Total abdominal perfusion (TAP) in the treatment of abdominal metastatic melanoma.
Total abdominal perfusion (TAP) is a recently described technique in which the abdominal organs are isolated from the systemic circulation and perfused by means of an external pump. Administering chemotherapy into the circuit provides higher locoregional drug exposure with lower systemic toxicity. Two patients with melanoma metastatic to the abdomen were treated using this technique. The first patient suffered from intractable upper gastrointestinal bleeding due to unresectable melanoma metastasis of the duodenum. He underwent TAP with melphalan and cisplatinum. His bleeding stopped and the tumor regressed. The patient's response lasted for 6 months. The second patient had an unresectable liver metastasis. She underwent TAP with melphalan and DTIC, resulting in a complete response with disappearance of the liver mass, which lasted until her death in 13 months. Our conclusion is that TAP should be considered as a technique for regional chemotherapy, which may be used in the treatment of unresectable metastatic melanoma of the abdomen.


Liquid biopsy and glioblastoma.
Glioblastoma is the most common and malignant primary brain tumor. Despite a century of research efforts, the survival of patients has not significantly improved. Currently, diagnosis is based on neuroimaging techniques followed by histopathological and molecular analysis of resected or biopsied tissue. A recent paradigm shift in diagnostics ranks the molecular analysis of tissue samples as the new gold standard over classical histopathology, thus correlating better with the biological behavior of glioblastoma and clinical prediction, especially when a tumor lacks the typical hallmarks for glioblastoma. Liquid biopsy aims to detect and quantify tumor-derived content, such as nucleic acids (DNA/RNA), circulating tumor cells (CTCs), or extracellular vesicles (EVs) in biofluids, mainly blood, cerebrospinal fluid (CSF), or urine. Liquid biopsy has the potential to overcome the limitations of both neuroimaging and tissue-based methods to identify early recurrence and to differentiate tumor progression from pseudoprogression, without the risks of repeated surgical biopsies. This review highlights the origins and time-frame of liquid biopsy in glioblastoma and points to recent developments, limitations, and challenges of adding liquid biopsy to support the clinical management of glioblastoma patients.


Deep neural network architectures for forecasting analgesic response.
Response to prescribed analgesic drugs varies between individuals, and choosing the right drug/dose often involves a lengthy, iterative process of trial and error. Furthermore, a significant portion of patients experience adverse events such as post-operative urinary retention (POUR) during inpatient management of acute postoperative pain. To better forecast analgesic responses, we compared conventional machine learning methods with modern neural network architectures to gauge their effectiveness at forecasting temporal patterns of postoperative pain and analgesic use, as well as predicting the risk of POUR. Our results indicate that simpler machine learning approaches might offer superior results; however, all of these techniques may play a promising role for developing smarter post-operative pain management strategies.


Regulation of Transforming Growth Factor β-Activated Kinase Activation by Epigallocatechin-3-Gallate in Rheumatoid Arthritis Synovial Fibroblasts: Suppression of K(63) -Linked Autoubiquitination of Tumor Necrosis Factor Receptor-Associated Factor 6.
Transforming growth factor β-activated kinase 1 (TAK1) is a key MAPKKK family protein in interleukin-1β (IL-1β), tumor necrosis factor (TNF), and Toll-like receptor signaling. This study was undertaken to examine the posttranslational modification of TAK1 and its therapeutic regulation in rheumatoid arthritis (RA). The effect of TAK1, IL-1 receptor-associated kinase 1 (IRAK-1), and TNF receptor-associated factor 6 (TRAF6) inhibition was evaluated in IL-1β-stimulated human RA synovial fibroblasts (RASFs). Western blotting, immunoprecipitation, and 20S proteasome assay were used to study the ubiquitination process in RASFs. The efficacy of epigallocatechin-3-gallate (EGCG), a potent antiinflammatory molecule, in regulating these processes in RASFs was evaluated. Molecular docking was performed to examine the interaction of EGCG with human TAK1, IRAK-1, and TRAF6. These findings were confirmed using a rat model of adjuvant-induced arthritis (AIA). Inhibition of TAK1, but not IRAK-1 or TRAF6, completely abrogated IL-1β-induced IL-6 and IL-8 synthesis in RASFs. EGCG inhibited TAK1 phosphorylation at Thr(184/187) and occupied the C(174) position, an ATP-binding site, to inhibit its kinase activity. EGCG pretreatment also inhibited K(63) -linked autoubiquitination of TRAF6, a posttranslational modification essential for TAK1 autophosphorylation, by forming a stable H bond at the K(124) position on TRAF6. Furthermore, EGCG enhanced proteasome-associated deubiquitinase expression to rescue proteins from proteasomal degradation. Western blot analyses of joint homogenates from rats with AIA showed a significant increase in K(48) -linked polyubiquitination, TAK1 phosphorylation, and TRAF6 expression when compared to naive rats. Administration of EGCG (50 mg/kg/day) for 10 days ameliorated AIA in rats by reducing TAK1 phosphorylation and K(48) -linked polyubiquitination. Our findings provide a rationale for targeting TAK1 for the treatment of RA with EGCG.


Acute appendicitis in the under-5 year old.
During a 10-year period we operated on 816 children with a diagnosis of acute appendicitis. Of these, 36 (4.5%) were under 5 years of age. A retrospective analysis was made of these 36 cases to assess the natural history, management and outcome in these children. Abdominal pain was the commonest symptom but was not invariable, being present in only 32 of the 36 children while vomiting was present in 28 children. Localized tenderness in the right iliac fossa was present in 21 children and generalized in 10. In 5 children there was a delay in diagnosis in excess of 18 h. The overall perforation rate was 50% as assessed macroscopically and was inversely proportional to the child's age. There was no mortality and the wound sepsis rate was 16.6%. The low incidence of acute appendicitis in very young children means that it is often overlooked. A high index of suspicion may contribute to earlier diagnosis and thereby reduce morbidity.


Co-constructed talk in the conversations of people with dysarthria and aphasia.
This paper uses the methodology of conversation analysis (CA) to examine the practice of co-constructed turn and utterance production in impaired communication. An investigation of the conversations between two family dyads, featuring one person with dysarthric speech and one with aphasic language, reveals one way in which single turns and utterances are produced through the collaborative activities of two people in interaction. Such a practice is shown to operate without problems for the participants or the need for explicit acceptance by the speakers. It is proposed that co-construction in disordered speech and language is one way in which communicative competence is accomplished. By drawing attention to similarities in the consequences of dysarthria and aphasia in everyday interaction, it is suggested that researchers and clinicians might profitably look across disorder-specific boundaries.


Urachal Mucinous Cystadenocarcinoma.
A 57-year-old man presented with a 6-month history of pelvic fullness. He had no lower urinary tract symptoms or altered bowel habits. On examination, there was a non-tender pelvic mass which extended from the pubic symphysis to the level of the umbilicus. CT scan of the abdomen demonstrated a 22×11×11 cm cystic mass arising from the pelvis extending into the midline and superiorly to the umbilicus. Other than raised carcinoembryonic antigen of 7.6 ng/mL (<5.0), the remainder of his blood test were unremarkable. Flexible cystoscopy demonstrated a convex deformity of the bladder wall in keeping with the compression and displacement as seen on the CT. The patient underwent an open excision of the cystic structure (urachal remnant), partial cystectomy, partial excision of anterior abdominal wall and pelvic lymphadenectomy. A check cystogram performed 12 days following the initial operation was unremarkable.


C lambda 2 and C lambda 4 immunoglobulin light chain genes in a wild-derived inbred mouse strain.
A genomic clone containing the lambda constant (C) region genes (C lambda 2S and C lambda 4S) has been isolated from a genomic library from the mouse strain SPE. SPE is an inbred strain derived from progenitors trapped near Grenada in Spain and has been classified as mus 3 or mus spretus. The sequence of the C lambda 2S gene is virtually identical to that of BALB/c both in the coding region and in flanking sequences, suggesting that it is an expressed gene in the SPE strain. By contrast, the C lambda 4S gene on the same cluster has diverged in sequence from that of BALB/c and contains a large deletion that precludes its normal expression. Whereas BALB/c J lambda 4 region contains substitutions that probably preclude its usage, the SPE J lambda 4 gene includes all sequences required for a functional J gene. Comparison of the C lambda 2S and C lambda 4S gene sequences with those available for BALB/c C lambda 3 and C lambda 1 confirms the close relationship between the C lambda 1-C lambda 4 and C lambda 2-C lambda 3 gene pairs. The C lambda 3 gene of BALB/c is more closely related to C lambda 2S than is C lambda 1 of BALB/c to C lambda 4S. If it is assumed that C lambda 1 and C lambda 2 are respective duplicates of C lambda 4 and C lambda 3 and that these duplications occurred at the same time, then the C lambda 2 gene has been under stronger selective pressure than C lambda 4.


Regioselective Arylboration of Isoprene and Its Derivatives by Pd/Cu Cooperative Catalysis.
A method for the regioselective arylboration of isoprene and its derivatives is presented. These reactions allow for the synthesis of useful building blocks from simple components. Through these studies, an unusual additive effect with DMAP has been uncovered that allows for altered reactivity and the formation of quaternary carbon centers. The utility of this method is demonstrated toward the formal synthesis of mesembrine.


Perlecan and tumor angiogenesis.
Perlecan is a major heparan sulfate proteoglycan (HSPG) of basement membranes (BMs) and connective tissues. The core protein of perlecan is divided into five domains based on sequence homology to other known proteins. Commonly, the N-terminal domain I of mammalian perlecan is substituted with three HS chains that can bind a number of matrix molecules, cytokines, and growth factors. Perlecan is essential for metazoan life, as shown by genetic manipulations of nematodes, insects, and mice. There are also known human mutations that can be lethal. In vertebrates, new functions of perlecan emerged with the acquisition of a closed vascular system and skeletal connective tissues. Many of perlecan's functions may be related to the binding and presentation of growth factors to high-affinity tyrosine kinase (TK) receptors. Data are accumulating, as discussed here, that similar growth factor-mediated processes may have unwanted promoting effects on tumor cell proliferation and tumor angiogenesis. Understanding of these attributes at the molecular level may offer opportunities for therapeutic intervention.


New records of Biemna Gray, 1867 (Biemnidae: Biemnida: Demospongiae) and a replacement name for the species Biemna microstyla Thomas, 1984.
Biemna Gray, 1867 is characterized by stylote or exceptionally oxeote megascleres arranged in a plumoreticulate skeleton, ectosomal skeleton consists of the brushed endings of choanosomal tracts, microscleres are sigmas, microxeas, commata and raphides (Hajdu Van Soest 2002). Currently, Biemna has 55 valid species (Van Soest et al. 2018). In Brazil, three species are known from northern region (Muricy 2018): Biemna microacanthosigma Mothes, Hajdu, Lerner Van Soest, 2004, Biemna spinomicroxea Mothes, Campos, Lerner, Carraro Van Soest, 2005, Biemna trisigmata Mothes Campos, 2004. In this present study, a new name is proposed for a preoccupied combination, Biemna thomasi nom. nov. The species Biemna caribea Pulitzer-Finali, 1986 is recorded and described for the first time in Brazilian waters. Six specimens of Biemna were studied in Pernambuco and Bahia States. All specimens were preserved in 80% ethanol and deposited on the Porifera Collections at the Universidade Federal de Pernambuco (UFPEPOR).


Diffusion of HDO in pure and acid-doped ice films.
In these experiments, a few bilayers of D(2)O were vapor-deposited on a pure crystalline H(2)O ice film or an ice film doped with a small amount of HCl. Upon deposition, H/D isotopic exchange quickly converted the D(2)O layer into an HDO-rich mixture layer. Infrared absorption spectroscopy followed the changes of the HDO from the initial HDO mixture layer to HDO isolated in the H(2)O ice film. This was possible because isolated HDO in H(2)O ice has a unique, sharp peak in the O-D stretch region that can be distinguished from the broad peak due to the initial HDO mixture layer. The absorbance of isolated HDO displayed first-order kinetics and was attributed to diffusion of HDO from the HDO-rich mixture layer into the underlying H(2)O ice film. While negligible diffusion was observed for pure ice films and for ice films with HCl concentrations up to 1 x 10(-4) mole fraction, diffusion of HDO occurred for higher concentrations of (2-20) x 10(-4) mole fraction HCl with a concentration-independent rate constant. The diffusion under these conditions followed Arrhenius behavior for T = 135-145 K yielding E(a) = 25 +/- 5 kJ/mol. The mechanism for the HDO diffusion involves either (i) molecular self-diffusion or (ii) long-range H/D diffusion by a series of multiple proton hop and orientational turn steps. While these spectroscopic results compare favorably with recent studies of molecular self-diffusion in low-temperature ice films, the diffusion results from all the ice film studies at low temperatures (ca. T < 170 K) differ from earlier bulk ice studies at higher temperatures (ca. T > 220 K). A comparison and discussion of the various diffusion studies are included in this report.


Self-assembly of silver nanoparticles as high active surface-enhanced Raman scattering substrate for rapid and trace analysis of uranyl(VI) ions.
A facile surface-enhanced Raman scattering (SERS) substrate based on the self-assembly of silver nanoparticles on the modified silicon wafer was obtained, and for the first time, an advanced SERS analysis method basing on this as-prepared substrate was established for high sensitive and rapid detection of uranyl ions. Due to the weakened bond strength of OUO resulting from two kinds of adsorption of uranyl species ("strong" and "weak" adsorption) on the substrate, the ν1 symmetric stretch vibration frequency of OUO shifted from 871cm-1 (normal Raman) to 720cm-1 and 826cm-1 (SERS) along with significant Raman enhancement. Effects of the hydrolysis of uranyl ions on SERS were also investigated, and the SERS band at ~826cm-1 was first used to approximately define the constitution of uranyl species at trace quantity level. Besides, the SERS intensity was proportional to the variable concentrations of uranyl nitrate ranging from 10-7 to 10-3molL-1 with an excellent linear relation (R2=0.998), and the detection limit was ~10-7molL-1. Furthermore, the related SERS approach involves low-cost substrate fabrication, rapid and trace analysis simultaneously, and shows great potential applications for the field assays of uranyl ions in the nuclear fuel cycle and environmental monitoring.


Health, medical risk factors, and bicycle use in everyday life in the over-50 population.
Few middle-aged and elderly people get enough exercise from sports or leisure-time physical activity. Therefore, the impact of everyday physical activity on health is a matter of interest. The main objective of this study was to establish whether bicycle use in everyday life is positively associated with health. A sample of 982 randomly selected men and 1,020 women age 50-70 were asked in a computer-assisted telephone interview to provide information including a self-assessment of their health and physical activity. Self-assessed health correlates positively with bicycle use in everyday life (OR = 1.257; 95% CI: 1.031-1.532). Likewise, people who regularly cycle for transport are less likely to have medical risk factors (OR = 0.794; 95% CI: 0.652-0.967). This negative correlation is not diminished when sporting activity is controlled for. This indicates that positive effects of physical activity on risk factors can be also achieved solely by integrating more physical activity into routine everyday life.


Quick report for psychiatric emergency rooms.
Translating and pre-digesting the volumes of data from a psychiatric emergency room database into a simple, easy-to-review "quick report" offers a different approach to a rapid review of patient information. Clinicians from psychiatric emergency rooms in New York City were asked to describe the minimal amount of information they would wish to review from previous clinical visits. The smallest report was then constructed to offer the most information.


Squaramide-catalysed asymmetric cascade aza-Michael/Michael addition reaction for the synthesis of chiral trisubstituted pyrrolidines.
A bifunctional squaramide catalysed aza-Michael/Michael cascade reaction between nitroalkenes and tosylaminomethyl enones or enoates has been developed. This organocatalytic cascade reaction provides easy access to highly functionalized chiral pyrrolidines with a broad substrate scope, giving the desired products in good yields (up to 99%) with good diastereoselectivities (up to 91 : 9 dr) and excellent enantioselectivities (up to >99% ee) under mild conditions. This protocol provides a straightforward entry to highly functionalized chiral trisubstituted pyrrolidine derivatives from simple starting materials.


Traveling waves in rotating Rayleigh-Bénard convection.
A combined analytical, numerical, and experimental study of the traveling-wave wall mode in rotating Rayleigh-Bénard convection is presented. No-slip top and bottom boundary conditions are used for the numerical computation of the linear stability, and the coefficients of the linear complex Ginzburg-Landau equation are then computed for various rotation rates. Numerical results for the no-slip boundary conditions are compared with free-slip calculations and with experimental data, and detailed comparison is made at a dimensionless rotation rate Omega=274. It is found that the inclusion of the more realistic no-slip boundary conditions for the top and bottom surfaces brings the numerical linear stability analysis into better agreement with the experimental data compared with results using free-slip top/bottom boundary conditions. Some remaining discrepancies may be accounted for by the finite conductivity of the sidewall boundaries.


The role of drug-coated balloons in in-stent restenosis.
Despite a constantly expanding spectrum of therapeutic options for lower limb artery disease, there is not yet a well-defined consensus on the specific type of endovascular treatment that is best suited. Clinical data on patients with femoropopliteal disease treated with drug-coated balloons have not been elaborated sufficiently, especially in the case of in-stent restenosis. For this review a systematic research of the medical databases (Pubmed) has been conducted. Keywords such as "drug-coated balloons" (DCB), "drug-eluting balloons," "in-stent restenosis", "de novo stenosis", "angioplasty", "superficial femoral artery," "popliteal artery," "above the knee," "below the knee," "peripheral artery disease" (PAD) have been used. Furthermore, data from reviews, original contributions regarding randomized controlled studies, observational studies, registries and single center experiences have been included. Many trials have shown superiority for DCB- over percutaneous transluminal angioplasty-treatment alone in TASC IIA and TASC IIB femoropopliteal lesions. However, the currently available DCB systems are different in terms of efficacy and long-term outcomes depending on their mechanical and pharmacological features. Moreover, angiographic characteristics of femoropopliteal lesions classified by Tosaka seem to influence subsequent outcomes of DCB treatment. Lastly, there is still lack of reliable prospective long-term data regarding DCB technology.


[Cardiotoxicity of Cancer Chemotherapy - Mechanisms and Therapeutic Approach].
Recent progress in cancer chemotherapy has improved the long-term outcome for cancer patients. Under such circumstances, it is increasingly of clinical importance to manage the cardiovascular complications, which are related to both cancer itself and adverse effects of cancer therapies. Among the most concerning as cardiovascular complications of cancer therapies is chemotherapy-induced cardiotoxicity or chemotherapy-related cardiac dysfunction(CTRCD). CTRCD has been intuitively classified according to the extent of structural abnormalities and degree of reversibility; type 1 is irreversible and dose-dependent with structural abnormalities, and type 2 is reversible after cessation of treatment and dose-independent without structural abnormalities. An example of drugs causing type 1 and 2 CTRCD is anthracyclines and trastuzumab, respectively, although both drugs are likely to induce cardiotoxicity through a combined action. In addition, there is growing awareness that CTRCD is also caused by anti-VEGF inhibitors and tyrosine kinase inhibitors(TKIs), particularly in patients with cardiovascular comorbidities and risk factors. Interdisciplinary collaboration between oncology and cardiology specialists will contribute to the solution of unmet needs to elucidate epidemiologic and pathophysiologic aspects of CTRCD and to establish diagnostic strategies with risk prediction and evidence-based therapeutic strategies against CTRCD in cancer patients and cancer survivors.


Studies on growth and cardenolide production of Digitalis lanata tissue cultures.
Digitalis lanata cell cultures grown as small undifferentiated aggregates in suspension culture can be redifferentiated into green embryos that produce cardenolides. The possibility of using a statistical (Box-Wilson) experimental design to study the effects of four different variables on growth, differentiation, and cardenolide production of D. lanata tissue cultures are investigated. The results of the analyses were processed by linear regression analysis. Mathematical models explaining the effects of the variables were developed. The concentration of maltose and the NO(3) (-)--NH(4) (+) ratio were found to be significant variables for both growth and cardenolide production. The size of the inoculum was also important.


[Phytoestrogens].
The soy-isoflavones genistein and daidzein and the flaxseed-lignans secoisolariciresinol and matairesinol belong to the group of phytoestrogens. Epidemiological data suggest that phytoestrogens have a preventive effect against various estrogen-related diseases/symptoms such as breast cancer, menopausal symptoms, cardiovascular diseases, and osteoporosis. To prove these assumptions, available controlled clinical trials have been critically reviewed. Especially soy-isoflavones have been extensively studied. There is no scientific evidence for an effect of phytoestrogens on menopausal symptoms and risk factors of breast cancer. However, isoflavones-containing soy protein can lower total cholesterol, LDL cholesterol, and triglyceride serum levels. The strongest evidence exists for a preventive effect of soy isoflavones on postmenopausal bone loss of the lumbar spine. Distinct effects on estrogen-related diseases can be explained at least in part by the different affinity of isoflavones to estrogen receptors alpha and beta and the distinct tissue distribution of these receptors.


Bismuth Telluride Nanoplates Hierarchically Confined by Graphene and N-Doped C as Conversion-Alloying Anode Materials for Potassium-Ion Batteries.
Potassium-ion batteries (PIBs) have broad application prospects in the field of electric energy storage systems because of its abundant K reserves, and similar "rocking chair" operating principle as lithium-ion batteries (LIBs). Aiming to the large volume expansion and sluggish dynamic behavior of anode materials for storing large sized K-ion, bismuth telluride (Bi2 Te3 ) nanoplates hierarchically encapsulated by reduced graphene oxide (rGO), and nitrogen-doped carbon (NC) are constructed as anodes for PIBs. The resultant Bi2 Te3 @rGO@NC architecture features robust chemical bond of Bi─O─C, tightly physicochemical confinement effect, typical conductor property, and enhanced K-ion adsorption ability, thereby producing superior electrochemical kinetics and outstanding morphological and structural stability. It is visually elucidated via high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) that conversion-alloying dual-mechanism plays a significant role in K-ion storage, allowing 12 K-ion transport per formular unit employing Bi as redox site. Thus, the high first reversible specific capacity of 322.70 mAh g-1 at 50 mA g-1 , great rate capability and cyclic stability can be achieved for Bi2 Te3 @rGO@NC. This work lays the foundation for an in-depth understanding of conversion-alloying mechanism in potassium-ion storage.


[The etiology and pathogenesis of infantile pyloric stenosis].
As it is known, pyloric stenosis among newborns and infants represents a high or complete obturation caused by stomach circular muscles hypertrophy. This disease is widely spread in the world. According to the reference data, the prevalence of this disease is about one per 200-300 newborns. Despite of the many surveys and investigations, ethiopathogenesis of pylorostenosis remains the issue of debates. Some of the authors consider pyloric stenosis as the innate defect of evolution, while others think that the enlargement of pylorus circular muscles is caused by working hypertrophy. According to our tests performed on the laboratory animals and developed experimental model of the disease, pyloric stenosis may be considered as an inborn pathology. The leading place in its etiology takes the partial impenetrability caused by the swelling of pylorus mucus (allergic, inflammation) and as a consequence development of working hypertrophy.


Strain echocardiographic assessment of ventricular function after percutaneous pulmonary valve implantation.
Percutaneous pulmonary valve implantation (PPVI) is an emerging therapy for pulmonary valve dysfunction. Minimal data on the midterm effects of PPVI on ventricular function exist. We describe the effects of PPVI on right and left ventricular (RV, LV) function with speckle tracking echocardiography. Patients who met the inclusion criteria of the Food and Drug Administration Phase 1 Feasibility Clinical Trial PPVI were identified. Patients were studied with echocardiograms at baseline, post-PPVI (day of discharge), 3 months, and at 6 months. Patients were studied by cardiac magnetic resonance at baseline and at 6 months. Longitudinal strain was measured at the basal, mid, and apical portions of the RV, interventricular septum (IVS), and LV. Global RV and LV strain and strain rates were recorded. Paired t-tests were used for analysis. Ten patients were analyzed: nine patients were a variant of tetralogy of Fallot and one patient had complex LV outflow obstruction requiring a Ross and RV-pulmonary atresia conduit. Mean age was 24.4 ± 7.6 years. Indication for PPVI was pulmonary regurgitation in six patients, stenosis in two patients, and stenosis/regurgitation in two patients. After PPVI, both RV systolic pressure and RV to pulmonary artery pressure gradient significantly decreased. Cardiac magnetic resonance RV end-diastolic volume significantly decreased. IVS-mid, IVS-apical, and LV-global strain significantly increased and RV-basal decreased immediately after PPVI. Global RV a' strain rate significantly increased immediately after PPVI. However, RV, IVS, and LV strain/strain rate values between baseline and the 6 month echocardiographic study were either similar or significantly decreased. Despite improvement in RV hemodynamics, there was a decrease or no improvement in RV and LV function as measured by strain echocardiographic values at midterm follow-up. Larger studies with longer follow-up are needed to determine if these results remain consistent.


Treatment with imipenem of experimental endocarditis caused by penicillin-resistant Streptococcus sanguis.
The efficacy of imipenem alone or in combination with gentamicin for the treatment of experimental endocarditis in rabbits caused by a penicillin resistant strain of Streptococcus sanguis was compared to that of gentamicin and penicillin G. In vitro, both beta-lactams were bactericidal in action and the combination of gentamicin and imipenem was synergistic after 4 h whereas penicillin G and gentamicin showed synergy after 8 h. Antibiotic treatment was started two days after initiating infection and groups of 20 animals were treated for 5 days with imipenem alone or in combination with gentamicin or with gentamicin and penicillin G. Two of 20 rabbits which received no therapy died whereas all other rabbits survived the treatment period. Blood cultures became negative in 19 rabbits on the second day of treatment with imipenem and gentamicin and sterilization of the vegetations was achieved in 12 animals. In contrast, eight animals given the alternative treatments remained bacteraemic and viable organisms were recovered from the vegetations in every case. However, bacterial counts and vegetation weights only differed significantly between treated animals and controls but not between the different treatment groups. Never the less, these data suggest that combined treatment with imipenem and gentamicin might provide an effective regimen for patients with endocarditis caused by penicillin resistant S. sanguis.


Statin use not associated with improved outcomes in patients treated with brachytherapy for prostate cancer.
To investigate the association between statin use and prostate cancer outcomes in intermediate- and high-risk patients treated with brachytherapy for prostate cancer. Between 1998 and 2010, 754 men with National Comprehensive Cancer Network intermediate- (n = 627) and high-risk (n = 127) prostate cancer were treated with prostate brachytherapy at our institution. Patients received either low-dose-rate or high-dose-rate brachytherapy as monotherapy or in combination with supplemental external beam radiotherapy. Two hundred eighty-five patients (37.8%) also received androgen-deprivation therapy. Two hundred seventy-three men (36.2%) were identified as taking statin medication before initiating radiation therapy. Prostate-specific antigen relapse-free survival (PSA-RFS), distant metastasis-free survival (DMFS), and overall survival were compared using log-rank tests. Associations of patient and treatment characteristics with outcomes were analyzed with univariate and multivariate regression. The median followup was 48 months. The 8-year PSA-RFS for intermediate-risk, high-risk, and all patients was 92.2%, 64.1%, and 87.7%, respectively. The 8-year DMFS was 97.1%, 82.9%, and 94.9%, respectively. The 8-year overall survival for the entire cohort was 86.6%. There were no significant differences between statin users and nonusers when stratified by risk group, nor when analyzed as a full cohort. On multivariate analysis, Gleason score 4 + 3 = 7 and >7 were significantly associated with worse PSA-RFS (p ≤ 0.003 and <0.001, respectively). Gleason score > 7 (p = 0.008) and the use of neoadjuvant androgen-deprivation therapy (p = 0.03) was associated with worse DMFS. Statin use did not significantly impact PSA-RFS or DMFS. Pretreatment statin use is not associated with improved outcomes in intermediate- and high-risk patients undergoing prostate brachytherapy-based regimens for prostate cancer.


Self-powered, autonomous Biological Oxygen Demand biosensor for online water quality monitoring.
Standard Biological Oxygen Demand (BOD) analysis requires 5 days to complete. To date, microbial fuel cell biosensors used as an alternative method for BOD assessment requires external apparatus, which limits their use for on-line monitoring in remote, off-grid locations. In this study, a self-powered, floating biosensor was developed for online water quality monitoring. This approach eliminated the need for external apparatus and maintenance that would otherwise be required by other techniques. The biosensor was able to detect urine in freshwater and turn ON a visual and sound cues (85 dB). The energy needed to operate the biosensor was produced by the system itself with the use of electroactive microorganisms, inside microbial fuel cells. The Chemical Oxygen Demand (COD) was used as a fast method of biosensor validation. When urine concentration exceeded the lower threshold, corresponding to a COD concentration of 57.7 ± 4.8 mgO2 L-1, the biosensor turned the alarm ON. The shortest observed actuation time, required to switch ON the alarm was 61 min, when the urine concentration was 149.7 ± 1.7 mgO2 L-1. Once the sensor was switched ON, the signal was emitted until the urine organic load decreased to 15.3 ± 1.9 mgO2 L-1. When ON, the microbial fuel cell sensor produced a maximum power of 4.3 mW. When switched OFF, the biosensor produced 25.4 μW. The frequency of the signal was proportional to the concentration of urine. The observed frequencies varied between 0.01 and 0.59 Hz. This approach allowed to correlate and quantitatively detect the presence of water contamination, based on signal frequency. The sensor was operating autonomously for 5 months. This is the first report of a self-powered, autonomous device, developed for online water quality monitoring.


Simultaneous assay for three types of thyrotropin receptor antibody activities using FRTL-5 cells in patients with autoimmune thyroid diseases.
The relationships between the different circulating thyrotropin receptor antibodies (TSH-R-abs) in autoimmune thyroid disease (AITD) are complex. In order to investigate them, we have developed an assay for the simultaneous measurement of three types of TSH-R-abs: TSH-binding inhibiting immunoglobulin (TBII): thyroid-stimulating antibody (TS-ab) and TSH-stimulation blocking antibody (TSB-ab). A large number of patients with Graves' disease (GD)--untreated and treated--Hashimoto's thyroiditis (HT), primary myxedema (PM) and non-immune goiter (NIG) were investigated. In untreated Graves' patients the frequency of positive TS-ab and TBII sera was found to be 90 and 69%, respectively, the presence of TS-ab and/or TBII being detected in 98%. After long-term antithyroid treatment administered to GD patients, the frequency of positivity of both TBII and TS-ab was decreased, whether hyperthyroidism was cured or not. The TSB-ab was detected in the serum of 8% of patients with GD, and the frequency of TSB-ab did not increase following treatment and alteration in thyroid function. No significant correlation was found between TSB-ab and thyroid function in Graves' patients. Besides, we found that all the GD patients presenting positive TSB-ab were also TBII positive. A follow-up study of the three TSH-R-abs was performed in 35 patients with GD during a mean of 14.3 +/- 8.5 months (4-34 months) of antithyroid drug treatment. Ten out of 24 patients (42%) with positive TBII and 16 out of 32 (50%) with positive TS-ab turned from positive to negative during the time of follow-up. Regarding relapse in hyperthyroid GD, we found that TS-ab was positive in 80% and TBII was positive in 40% of the patients with Graves' relapse, indicating that the presence of TS-ab is a better index for relapse prediction in Graves' hyperthyroidism than TBII. The TSB-ab was found with higher frequency in HT and PM than in GD, i.e. 21%, 18% and 8%, respectively., The TSB-ab positivity was correlated significantly with TBII in our patients with AITD when TSB-ab was positive. This new simultaneous assay of the three TSH-R-abs should be very helpful for further investigation of the autoimmune aspects of AITD and it should help us to progress in a better understanding of the pathogeny of the different AITDs.


The Relationship between Childhood Maltreatment and Emotional Dysregulation in Self Mutilation: An Investigation among Substance Dependent Patients.
The present study aims to examine the role of emotion dysregulation and childhood maltreatment in self mutilation (SM) of substance dependent patients. Specifically, the present study examined whether emotion dysregulation and its dimensions, and childhood maltreatment and its dimensions were associated with SM. The relationship between emotion dysregulation and childhood maltreatment was also investigated. The sample of study consisted of 55 alcohol dependent and 24 opiate dependent patients (n=79). Substance dependence was diagnosed by means of the Structured Clinical Interview for DSM-IV-TR (SCID-I), Turkish version. Childhood Trauma Questionnaire (CTQ) and Difficulties in Emotion Regulation Scale (DERS) were used. Findings indicated that substance dependents with SM and without SM were differentiated in terms of overall emotion dysregulation. Results also suggest the relevance of three specific dimensions of emotion dysregulation to SM: Difficulties engaging in goal-directed behaviors when experiencing negative emotions, difficulties controlling impulsive behaviors when experiencing negative emotions, and limited access to effective emotion regulation strategies. These dimensions were predicted from childhood emotional maltreatment and neglect. It is also revealed that substance dependents with SM had higher points than those without SM on emotional childhood maltreatment and neglect, physical childhood maltreatment. Results were supported by the literature suggested that self-mutilation functions as a emotional regulation strategy. Findings also suggested that self- mutilation is related to early relationships take place in family environment in which individuals grow up.


Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle.
A 26 amino acid synthetic peptide fragment of atrial natriuretic factor (ANF) relaxed isolated rabbit aortic segments in which the endothelium was either intact or functionally destroyed. The relaxations were temporally associated with increases in levels of cGMP with no change in the levels of cAMP. The ANF-induced increases in cGMP were also observed in aortic segments pretreated with calcium-free buffer or the cGMP phosphodiesterase inhibitor M&B 22,948. Qualitatively similar results were obtained for sodium nitroprusside. ANF selectively activated particulate guanylate cyclase, having no effect on the soluble form of the enzyme. Thus, the direct (endothelium-independent) vasodilator effect of ANF may be mediated via increased tissue levels of cGMP. ANF appears to increase vascular cGMP levels by activation of particulate guanylate cyclase.


Coping, symptoms, and functioning outcomes of patients with posttraumatic stress disorder.
This study examines the association between approach coping and better functioning outcomes and the reciprocal relationships between coping and posttraumatic stress disorder (PTSD) symptoms in patients diagnosed with PTSD. Posttraumatic stress disorder patients receiving services in five VA health care systems were randomly selected and surveyed at baseline and followed 10 months later. Analyses of longitudinal data using structural equation modeling techniques showed that more approach coping predicted better family and social functioning. Cognitive avoidance coping predicted more PTSD symptoms, and more PTSD symptoms predicted more approach coping and more behavioral avoidance coping. Approach coping may enable patients with chronic PTSD to establish and maintain better relationships with family and friends, despite continuing PTSD.


Lack of iNKT cells in patients with combined immune deficiency due to hypomorphic RAG mutations.
Hypomorphic mutations of the RAG genes in humans are associated with a spectrum of clinical and immunologic presentations that range from T(-) B(-) severe combined immune deficiency (SCID) to Omenn syndrome. In most cases, residual V(D)J recombination activity allows for development of few T-cell clones, which expand in the periphery and infiltrate target organs, resulting in tissue damage. Invariant natural killer T (iNKT) cells play an important immunoregulatory role and have been associated with protection against autoimmunity. We now report on 5 unrelated cases of combined immune deficiency due to hypomorphic RAG mutations, and demonstrate the absence of iNKT cells in all 5 patients. These findings suggest that lack of this important immunoregulatory cell population may contribute to the pathophysiology of Omenn syndrome.


Attitudes of physical therapists who possess sports specialist certification.
Physical therapists contemplating sports specialist certification need research-based information to facilitate their decision-making process. The purpose of this study was to investigate the attitudes of physical therapists who have received sports specialist certification. These attitudes encompass the physical therapists' sense of fulfillment and their feelings of satisfaction or dissatisfaction with the certification process. Factors contributing to the therapist's decision to become sports specialist certified have also been investigated. Physical therapists who are sports certified specialists (N = 110) participated in this study. Questionnaires were mailed to the entire population of physical therapists who are sports certified specialists (N = 148). Frequency distributions and percentages were used on qualitative data, and mode was calculated for quantitative data. One hundred ten surveys were returned, for a response rate of 74.3%. Analysis of responses from the subject group suggests that physical therapists feel a high level of satisfaction with their decision to specialize, and that continued professional growth, development, and personal achievement are the major contributing factors in their decision to specialize. Based on these findings, physical therapists appeared to display overall satisfaction in their attitudes toward sports specialist certification. Further research may be warranted to further examine sports certified therapists' attitudes toward the specialization process.


Analysis of five novel putative constitutive gene promoters in transgenic rice plants.
Novel constitutive gene promoters are essential components of crop biotechnology. Our analysis of five such promoters, APX, SCP1, PGD1, R1G1B, and EIF5, in transgenic rice plants is reported here. The five promoter regions were linked to the gfp reporter gene and transformed into rice. Using fluorescent microscopy and q-RT-PCR, promoter activities were analysed in comparison with OsCc1, Act1, and ZmUbi1, previously characterized as strong constitutive promoters. The APX and PGD1 promoters direct high levels of gene expression in all tissues and stages, producing GFP at levels of up to 1.3% of the total soluble protein. PGD1 is particularly active in flowers and mature roots. The R1G1B is active in the whole grain including the embryo, endosperm, and aleurone layer, and thus represents a constitutive promoter with activity in whole seeds that has not been described previously. The ZmUbi1 and R1G1B promoters are markedly less active in young roots and mature leaves whilst the APX, PGD1, OsCc1, and Act1 promoters are highly active in both vegetative and reproductive tissues. Overall, our results demonstrate that APX, PGD1, and R1G1B are novel gene promoters that are highly active at all stages of plant growth with distinct levels of activity.


Polypharmacy in outpatients with relapsing-remitting multiple sclerosis: A single-center study.
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system. Given the chronic and heterogenous nature of the disease, treatment with various therapies is a frequent scenario in clinical practice. In persons with chronic morbidity such as MS patients, polypharmacy can give rise to considerable health problems. The aim of the present study was to examine the frequency of polypharmacy among relapsing-remitting (RR) MS patients as well as to analyse sociodemographic and clinical factors, which might be associated with polypharmacy (use of five or more medications). Differences in medication between MS patients with and without secondary illnesses (PwSI and Pw/oSI), between men and women and between patients with and without polypharmacy (PwP and Pw/oP) were examined. For 145 RRMS outpatients, we prospectively collected data by means of anamnesis, patient records, clinical examination and a structured patient interview. This was followed by comparative analyses of various patient subgroups (PwP vs. Pw/oP, PwSI vs. Pw/oSI, men vs. women). The proportion of included MS patients with polypharmacy (use of ≥5 medications) was 30.3%. PwP were significantly older than Pw/oP (45.9 vs. 41.7 years), had a lower level of education and showed a significantly higher median EDSS score (3.0 vs. 2.0). Comorbidities (p<0.001; odds ratio [OR] = 6.293) and higher EDSS scores (p = 0.029; OR = 1.440) were associated with a higher risk of polypharmacy. The proportion of polypharmacy among PwSI was approximately four times higher than among Pw/oSI (46.8% vs. 11.8%). Particularly in the use of antihypertensives, gastrointestinal drugs and dietary supplements, there were differences between Pw/oP and PwP. We found a high burden of polypharmacy in patients with RRMS. This particularly applies to more severely disabled MS patients who suffer from comorbidities.


Prevalence and gB genotype distribution of human cytomegalovirus among HIV sero-negative and HIV sero-positive orphans in Thailand.
Human Cytomegalovirus (HCMIV infects humans in all geographic areas. Polymorphisms ofglycoprotein B (gB) have been usedforgenotypic characterization of HCMV However information of gB genotyping of HCMV in Thailand is not clearly known especially in children. A cross-sectional study was conducted to assess HCMV infection in 236 HIV seronegative and HIV seropositive children who attended an orphanage in Nonthaburi, Thailand by nested-PCR technique using urine specimens. HCMV gB genotypes were determined by restrictionfragment length polymorphism (RFLP), andDNA sequencing technique. Sixty-one percent (144/236) of the samples were HCMV positive, which consisted of 66.1% (37/56) of the HIV seropositive children and 59.4% (107/180) of the HIVsero-negative children. Multivariate analysis showed that children who living in one particular room were independently associated with HCMVinfection. Genotypic analysis revealed that the most prevalent genotype in these children was gB1; 85.4% (111/130) followed by gB3; 4.6% (6/130), gB2 and gB4 each at 2.3% (3/130). Mixed gB genotypes were identified in 5.4% (7/130) of the samples. HCMV infection, in particular gB1 genotype was commonly ident fled among these Thai orphans. Living in one particular room was associated with getting the infection. To prevent the transmission of HCMV infection in this setting, improvement in hygienic behavior ofchildcare workers should be focused.


Evidence implicating eating as a primary driver for the obesity epidemic.
This article addresses the extent to which increases in energy intake as opposed to decreases in energy expenditure are driving the obesity epidemic. It argues that while both intake and expenditure are plausible and probable contributors, the fact that all intake is behavioral, whereas less than half of expenditure is behavioral, makes intake a conceptually more appealing primary cause. A review of per capita food disappearance trends over time and of trends in individual intakes is presented to support the plausibility of this perspective. Increases in energy intake mirror increases in body weight quantitatively and are equally widely distributed across diverse groups within the larger population.


Overview of the mechanisms regulating chemokine activity and availability.
Physiological leukocyte homing and extravasation of leukocytes during inflammatory processes is directed by a number of proteins including adhesion molecules, proteases, cytokines and chemokines. Tight regulation of leukocyte migration is essential to ensure appropriate migration. A number of mechanisms exist that regulate leukocyte migration including up- or down-regulation of chemokine or chemokine receptor gene expression. However, chemokine availability in vivo also depends on the interaction of chemokines with specific glycosaminoglycans such as heparan sulfate on the surface of endothelial layers. Modification of the interaction of chemokines with these glycosaminoglycans alters the presentation of chemokines to chemokine receptors on circulating leukocytes. On top, binding of chemokines to atypical chemokine receptors that do not signal through G proteins affects chemokine availability on the endothelial layers. In addition to mechanisms that modulate chemokine availability, this review summarizes mechanisms that fine-tune chemokine function. These include synergy or antagonism between chemokines and alternative splicing of chemokine genes. Moreover, chemokines may be posttranslationally modified leading to molecules with enhanced or reduced potency to bind to G protein-coupled receptors or GAGs or generating chemokines with altered receptor specificity. Cross-talk between these different mechanisms generates a complex regulatory network that allows the organism to modulate leukocyte migration in a highly specific manner.


CRITERIA OF FEMALE MATE CHOICE IN DROSOPHILA LITTORALIS, D. MONTANA, AND D. EZOANA.
We examined sexual selection by Drosophila littoralis, D. montana, and D. ezoana females on male courtship sounds to determine whether the females use absolute or relative criteria when choosing their mates. Behavior of the females was observed, when they were courted by a single male producing normal sounds, or by a single wing-manipulated male producing abnormal sounds; and when they were courted by one or both of these males in a choice situation. The females usually accepted short-winged (but not wingless) males producing abnormal sounds, if they had no alternatives. However, if they heard the sound produced by a normal male, they rejected the deficient male. Drosophila littoralis and D. ezoana females selected between two wing-manipulated males with different wing areas. Our results suggest that the females choose their mates on the basis of relative criteria if the signals emitted by the courting males are within the range of acceptable cues.


Blood-brain barrier imaging and therapeutic potentials.
Much work has been done in the last several decades to improve the understanding of the molecular composition of the blood-brain barrier (BBB). Advances in magnetic resonance imaging have resulted in development of dynamic magnetic resonance imaging techniques to quantify permeability measurements across the brain endothelium. This review describes the basic anatomical and biochemical concepts of a BBB and the various techniques for magnetic resonance measurement of BBB permeability. To date, BBB permeability data have been shown to be useful in preoperative brain tumor grading and potentially also in determining the effectiveness of selective types of therapy. Explorative studies are evaluating new strategies for safe and effective altering of the BBB permeability to improve local drug delivery into brain tumors. As new antiangiogenesis drugs become available, BBB permeability imaging may also become critical as a surrogate angiogenesis marker to monitor tumor response to these agents. Finally, BBB permeability data may also prove useful in future applications to guide therapy in other nontumoral disease processes such as acute cerebral ischemia and inflammatory processes such as multiple sclerosis.


Sulfonamide-resistant bacteria and their resistance genes in soils fertilized with manures from Jiangsu Province, Southeastern China.
Antibiotic-resistant bacteria and genes are recognized as new environmental pollutants that warrant special concern. There were few reports on veterinary antibiotic-resistant bacteria and genes in China. This work systematically analyzed the prevalence and distribution of sulfonamide resistance genes in soils from the environments around poultry and livestock farms in Jiangsu Province, Southeastern China. The results showed that the animal manure application made the spread and abundance of antibiotic resistance genes (ARGs) increasingly in the soil. The frequency of sulfonamide resistance genes was sul1 > sul2 > sul3 in pig-manured soil DNA and sul2 > sul1 > sul3 in chicken-manured soil DNA. Further analysis suggested that the frequency distribution of the sul genes in the genomic DNA and plasmids of the SR isolates from manured soil was sul2 > sul1 > sul3 overall (p<0.05). The combination of sul1 and sul2 was the most frequent, and the co-existence of sul1 and sul3 was not found either in the genomic DNA or plasmids. The sample type, animal type and sampling time can influence the prevalence and distribution pattern of sulfonamide resistance genes. The present study also indicated that Bacillus, Pseudomonas and Shigella were the most prevalent sul-positive genera in the soil, suggesting a potential human health risk. The above results could be important in the evaluation of antibiotic-resistant bacteria and genes from manure as sources of agricultural soil pollution; the results also demonstrate the necessity and urgency of the regulation and supervision of veterinary antibiotics in China.


Flap monitoring by transcutaneous PO2 and PCO2: importance of transcutaneous PCO2 in determining follow-up treatment for compromised free flaps.
The authors conducted a two-part study to determine whether transcutaneous oxygen pressure (TcPO (2)) and transcutaneous carbon dioxide pressure (TcPCO (2)) can be used to monitor flap viability after transplantation. The first part was an animal study in which TcPO (2) and TcPCO (2) were measured in 10 epigastric island flaps subjected to arterial or venous ischemia. The second part was a clinical study in which both were measured in 27 free skin flaps. In the experimental study, TcPO (2) decreased to nearly 0 mmHg after 10 minutes of arterial and venous ischemia. TcPCO (2) increased to 100 mmHg after 60 minutes of either type of ischemia. In the clinical study, congestion was suspected in six flaps on the basis of clinical signs alone. Three congested flaps with TcPCO (2) more than 90 mmHg were selected for intervention. The remaining three congested flaps, with TcPCO (2) 80 mmHg or less, survived completely without further treatment. The TcPO (2) of all treated flaps and of the six flaps not requiring further treatment was 0 mmHg. Results of experimental study indicate that TcPO (2) is more sensitive than TcPCO (2) to flap ischemia. However, results of clinical study suggest that it is very hard to distinguish congested flaps from healthy flaps by TcPO (2) alone. The authors believe that a congested flap with a TcPCO (2) more than 90 mmHg requires further treatment.


Development of targeted therapies for B-cell non-Hodgkin lymphoma and multiple myeloma.
The design of innovative, more effective, and less toxic therapy of B-cell lymphoma is emerging in parallel to a better understanding of the mechanisms of action of target-specific agents targeting the neoplastic B cell. Rituximab has changed the treatment paradigm of patients with B-cell lymphomas and is considered the first effective targeted therapy approved by the US Food and Drug Administration (FDA) for the treatment of lymphoproliferative disorders. Despite its good efficacy and safety profile, sustained complete remissions have been documented in a relatively small proportion of patients treated with rituximab monotherapy. To improve antitumor activity, initial strategies combined rituximab with standard chemotherapy drugs which led to higher response rates and improvement in disease-free and in some cases (ie, diffuse large B-cell lymphoma) prolongation of overall survival. While rituximab has been incorporated into multiple chemotherapy regimens (ie, CVP, CHOP, FND, etc.) a significant number of lymphoma patients either relapse after initial responses or fail to respond as a consequence of either intrinsic or acquired resistance. Scientific efforts are being focused toward developing new strategies to improve rituximab activity. In this report we provide an overview of recent developments in target-specific therapies and review past, ongoing, and future research tiling this diverse group of exciting novel agents.


[Care pathway of children managed by the Bouches-du-Rhone Child Welfare Services].
To describe the care pathway of children managed by the Bouches-du-Rhône Child Welfare Services and to propose ways to improve this care pathway. ESSPER-ASE 13 survey is a descriptive and cross-sectional survey carried out between April 2013 and April 2014, which included 1,092 children under the age of 18 years placed in a Bouches-du-Rhône Child Welfare Services children's home or foster care. This survey studied the physical and mental health and the medical follow-up characteristics of these children. This article focuses on care pathway data. 82% of children were followed by general practitioners, while 15% of children, essentially children under the age of 6 years in child care, were followed by Maternal and Infant Protection (Protection Maternelle et Infantile). The care pathway of these children involved multiple actors and was dominated by psychological follow-up. On average, the children were followed by 2 professionals (specialist or paramedical professional) in addition to the medical examiner. In terms of prevention, children's immunization coverage rates were better than national rates. Coordination of the numerous actors is essential, including the creation of a referring physician.


Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice.
The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using forced swim test (FST). In sub-acute study (21 times with 24-h intervals), antidepressant-like effects of oral administration of drugs were examined using FST and tail suspension test (TST). Locomotor activity and motor coordination were studied using open field and rotarod tests, respectively. Acute treatment with crocin (40 mg/kg) and crocetin (20 and 40 mg/kg) produced antidepressant-like effect in FST without affecting the baseline locomotion in mice. Sub-acute oral administration of crocin significantly decreased immobility time only at the highest dose (100 mg/kg). Crocetin (12.5, 25 and 50 mg/kg) was able to decrease immobility time in FST and TST. Locomotor activity and coordination of mice were not affected by crocin or crocetin. Since higher doses of crocin was required to show antidepressant effects, more efficacy of crocetin may be concluded. This observation provides further support for metabolism of crocin to crocetin following oral administration.


Water-Induced Self-Assembly of Amphiphilic Discotic Molecules for Adaptive Artificial Water Channels.
Inspired by the induced-fit mechanism in nature, we developed the process of water-induced self-assembly (WISA) to make water an active substrate that regulates the self-assembly and function of amphiphilic discotic molecules (ADMs). The ADM is an isotropic liquid that self-assembles only when in contact with water. Characterization results indicate that water fits into the hydrophilic core of the ADMs and induces the formation of a hexagonal columnar phase (Colh), where each column contains a hydrated artificial water channel (AWC). The hydrated AWCs are adaptive rather than static; the dynamic incorporation/removal of water results in the reversible assembly/disassembly of the adaptive AWCs (aAWCs). Furthermore, its dynamic characteristics can enable water to act as an orientation-directional guest molecule that controls the growth direction of the aAWCs. Well-aligned aAWC arrays that showed the ability of water transport were obtained via a "directional WISA" method. In WISA, water thus governs the supramolecular chemistry and function of synthetic molecules as it does with natural materials. By making water an active component in adaptive chemistry and enabling host molecules to dynamically interact with water, this adaptive aquatic material may motivate the development of synthetic molecules further toward biomaterials.


Nocturnal hypoxemia, night-day arterial pressure changes and left ventricular geometry in dialysis patients.
It is well established that nocturnal hypoxemia in sleep apnea causes an inversion of the circadian arterial pressure rhythm and triggers nocturnal hypertension. Since sleep apnea is very frequent in dialysis patients, we hypothesized that nocturnal hypoxemia may be a factor that contributes to alter the 24-hour arterial pressure profile in these patients. To test the hypothesis 32 dialysis patients underwent 24-hour blood pressure (BP) monitoring and continuous monitoring of arterial O2 saturation during the night-time. Hemodialysis patients were studied during the non-dialysis day. All patients underwent an echocardiographic study. Thirteen patients had no episode of nocturnal hypoxemia (group I), 7 had at least one episode overnight but less than 2 episodes/hr (group II) and 12 had > or = 2 episodes/hr (group III). The average daytime systolic pressure was similar in the three groups. However, the average nocturnal systolic pressure fell in the first group (-2.5 +/- 4.2%) and rose in the second (+2.0 +/- 3.6%) and in the third (+3.9 +/- 2.2%) group (one way ANOVA, P < 0.005). The relative wall thickness of the left ventricle (RWT) was significantly (P < 0.05) higher in group III than in group I, and in the aggregate (N = 32) there was an inverse relationship between average nocturnal SaO2 and RWT (r = -0.43, P = 0.015). The proportion of patients with concentric remodeling or concentric hypertrophy was higher (P = 0.05) in the group with a more severe degree of nocturnal hypoxemia (group III, 8 of 12) than in the other two groups (group I, 3 of 13; group II, 2 of 7). Nocturnal hypoxemia is associated with the "non-dipping" arterial pressure profile in dialysis patients. Disturbed respiratory control during the night may represent an important cardiovascular risk factor in dialysis patients.


[Trazodone and venlafaxine in treatment of depressive disorders].
In depressive disorders treatment a variety of antidepressant drugs is applied. Tricyclic antidepressant drugs are relatively well known together with selective serotonin reuptake inhibitors group. The aim of the study was to evaluate trazodone efficiency and safety in comparison to venlafaxine treatments of depressive episode, recurrent depressive disorders and depressive episode in bipolar disorders. 115 patients were involved in the study. The research lasted 42 days. There were no essential differences between the control group of patients at the beginning of the study. The final result was 11.4 +/- 8.1 according to HAMD-S scale in trazodone group and 11.9 +/- 8.0 in venlafaxine group. Significant improvement evaluated in HAMD-S and CGI scale was observed in 61.4% patients trazodone treated and 59.4% in venlafaxine group. At the beginning of the treatment some patients suffered from unwanted symptoms. In venlafaxine group the most common were libido decrease up to 12.9% and gastro-intestinal dysfunction in 11.3%. In trazodone group the most common symptom was gastro-intestinal dysfunction in 5.6%. Due to severe unwanted symptoms the treatment was stopped in 12.9% patients venlafaxine treated and in 7.4% patients treated by trazodone. Our study showed similar efficiency and safety of trazodone and venlafaxine for depression disorders. Trazodone efficiency in comparison to venlafaxine was faster, especially in 14th study day. It suggests that trazodone characterized by potentially quicker beginning of activity in patients with depression disorders.


[Normalized diagnosis and treatment of small penis: Advances in studies].
Small penis is abnormal development of the male external genitalia with unknown etiology. It is closely related to abnormal endocrine or pubertal development, chromosomal or genetic abnormalities. Pubertal growth retardation and secondary hypogonadism are commonly complicated by small penis or small testis; primary hypogonadal lesion develops in the testis; testosterone deficiency often results in small penis and short stature; sexual dysfunction and male infertility tend to occur in adult men. Attention should be paid to the four aspects concerning the clinically standardized diagnosis and treatment of small penis, namely, accurate measurement of the stretched penile length, active screening of possible causes, diagnosis and differential diagnosis, and active and effective clinical interventions for the purpose of increasing the penile length and improving the prognosis, patient's quality of life, and natural pregnancy rate.


Heart valve replacement with CarboMedics bileaflet prosthesis: surgical results and clinical evaluation. A medium term follow-up.
From March 1990 to July 1991, 110 patients (44 males, 66 females; mean age 54.44 +/- 8.8 years) underwent hearth valve replacement with a CarboMedics bileaflet prosthesis (CarboMedics Inc, Texas, USA). Preoperative pathophysiologic conditions were: aortic stenosis in 32 patients, aortic regurgitation in 22 patients; mitral stenosis in 27 patients and mitral regurgitation in 14 patients. Mitroaortic disease was present in 14 patients but 1 had triple valve disease. NYHA class was III or IV in 91 patients (83%). Operative mortality rate was 0.91% (1 patients). Actuarial survival rate is 95% at 58 months. Actuarial freedom from thromboembolic events in 95% at 58 months. Actuarial freedom from hemorrhage is 100%. Endocarditis befell in 2 patients; actuarial freedom from this complication at 58 months is 95%. Actuarial freedom from reoperation in 99%. We conclude that the low incidence of valve related events and the low mortality supports the use of the bileaflet valve CarboMedics.


Drain vs. no drain in primary thyroid and parathyroid surgery.
The need for drainage after primary thyroid or parathyroid surgery was evaluated in a prospective study in which 100 consecutive patients were randomly allocated to drainage or no drainage. Seroma developed in the wound in seven of the 50 patients without drainage and in two of the 50 with drainage. There were no residual effects of the seromas, which resolved spontaneously. The incidence of wound complication was unrelated to the surgeon's opinion on the need for drainage. The study provided no statistical report for routine use of drains in primary thyroid or parathyroid surgery.


HPV Prevalence in Multiple Anatomical Sites among Men Who Have Sex with Men in Peru.
Human Papilloma Virus (HPV) infection is the most common sexually transmitted viral infection worldwide. HPV is highly prevalent in sexually active men who have sex with men (MSM) and has been associated with anal cancer, penile cancer, and oropharyngeal cancer. From March to September 2011, we conducted a cross-sectional study of HPV prevalence among MSM above age 18 years. Participants were recruited using respondent driven sampling at Clinica Cayetano Heredia. All participants provided anal, genital, and oral samples for HPV DNA testing, and blood for HIV and HPV antibody testing. A total of 200 MSM were recruited in the study. The mean age was 34 years (range 18-59 years, SD = 9.4) and101 participants were HIV negative (99 HIV positive). HPV 6/11/16/18 or quadrivalent HPV vaccine (HPV4) genotype seroprevalence among HIV negative and positive MSM was 64.3% (55%-75.9%) and 93.8% (87.6%-99.2%) respectively (p<0.001). HIV positivity was associated with a higher prevalence of HPV4 and HPV 16/18 DNA at external genital sites and the anal canal. HPV4 DNA prevalence at external genital sites among HIV negative and positive MSM was 14.9% and 28.7% (p = 0.02) respectively, at anal canal was 50.9% and 79.0% (p = 0.001), and at the oral cavity was 9.9% and 8.5% (p = 0.6). HPV4 seroprevalence was high in our study among both HIV positives and negatives, with HPV DNA prevalence much lower, and the anal canal being the anatomical site with the highest HPV DNA prevalence. HPV prevention interventions are needed among MSM at high-risk for HIV infection.


Towards a specific reaction parameter density functional for reactive scattering of H2 from Pd(111).
Recently, an implementation of the specific reaction parameter (SRP) approach to density functional theory (DFT) was used to study several reactive scattering experiments of H2 on Cu(111). It was possible to obtain chemical accuracy (1 kcal/mol ≈ 4.2 kJ/mol), and therefore, accurately model this paradigmatic example of activated H2 dissociation on a metal surface. In this work, the SRP-DFT methodology is applied to the dissociation of hydrogen on a Pd(111) surface, in order to test whether the SRP-DFT approach is also applicable to non-activated H2-metal systems. In the calculations, the Born-Oppenheimer static surface approximations are used. A comparison to molecular beam sticking experiments, performed at incidence energies ≥125 meV, on H2 + Pd(111) suggested the PBE-vdW [where the Perdew, Burke, and Ernzerhof (PBE) correlation is replaced by van der Waals correlation] functional as a candidate SRP density functional describing the reactive scattering of H2 on Pd(111). Unfortunately, quantum dynamics calculations are not able to reproduce the molecular beam sticking results for incidence energies <125 meV. From a comparison to initial state-resolved (degeneracy averaged) sticking probabilities it seems clear that for H2 + Pd(111) dynamic trapping and steering effects are important, and that these effects are not yet well modeled with the potential energy surfaces considered here. Applying the SRP-DFT method to systems where H2 dissociation is non-activated remains difficult. It is suggested that a density functional that yields a broader barrier distribution and has more non-activated pathways than PBE-vdW (i.e., non-activated dissociation at some sites but similarly high barriers at the high energy end of the spectrum) should allow a more accurate description of the available experiments. Finally, it is suggested that new and better characterized molecular beam sticking experiments be done on H2 + Pd(111), to facilitate the development of a more accurate theoretical description of this system.


Mesenchymal Stem Cells in Premature Ovarian Insufficiency: Mechanisms and Prospects.
Premature ovarian insufficiency (POI) is a complex endocrine disease that severely affects the physiological and reproductive functions of females. The current conventional clinical treatment methods for POI are characterized by several side effects, and most do not effectively restore the physiological functions of the ovaries. Transplantation of mesenchymal stem cells (MSCs) is a promising regenerative medicine approach, which has received significant attention in the management of POI with high efficacy. Associated pre-clinical and clinical trials are also proceeding orderly. However, the therapeutic mechanisms underlying the MSCs-based treatment are complex and have not been fully elucidated. In brief, proliferation, apoptosis, immunization, autophagy, oxidative stress, and fibrosis of ovarian cells are modulated through paracrine effects after migration of MSCs to the injured ovary. This review summarizes therapeutic mechanisms of MSCs-based treatments in POI and explores their therapeutic potential in clinical practice. Therefore, this review will provide a theoretical basis for further research and clinical application of MSCs in POI.


Ag+ -Doped InSe Nanosheets for Membrane Electrode Assembly Electrolyzer toward Large-Current Electroreduction of CO2 to Ethanol.
It is an appealing approach to CO2 utilization through CO2 electroreduction (CO2 ER) to ethanol at high current density; however, the commonly used Cu-based catalysts cannot sustain large current during CO2 ER despite their capability for ethanol production. Herein, we report that Ag+ -doped InSe nanosheets with Se vacancies can address this grand challenge in a membrane electrode assembly (MEA) electrolyzer. As revealed by our experimental characterization and theoretical calculation, the Ag+ doping, which can tailor the electronic structure of InSe while diversifying catalytically active sites, enables the formation of key reaction intermediates and their sequential evolution into ethanol. More importantly, such a material can well work for large-current conditions in MEA electrolyzers with In2+ species stabilized via electron transfer from Ag to Se. Remarkably, in an MEA electrolyzer by coupling cathodic CO2 ER with anodic oxygen evolution reaction (OER), the optimal catalyst exhibits an ethanol Faradaic efficiency of 68.7 % and a partial current density of 186.6 mA cm-2 on the cathode with a full-cell ethanol energy efficiency of 26.1 % at 3.0 V. This work opens an avenue for large-current production of ethanol from CO2 with high selectivity and energy efficiency by rationally designing electrocatalysts.