Is there benefit in implanting defibrillators in patients with severe heart failure?
It is current practice to withhold implantable cardioverter defibrillators (ICD) from patients with severe heart failure because their deaths are judged as non-sudden and therefore assumed not to be preventable by ICD. If this was true, there should be a trend towards reduced preventability of deaths in the severe heart failure subgroups within existing randomised control ICD trials. We tested the prevailing assumption that patients with most severe heart failure would not benefit from ICD implantation. METHODS Six trials were identified enrolling 7873 patients, with 2734 patients randomly assigned to receive an ICD. Reduction in mortality in the ICD arm varied between 5.6% and 31%. All six trials provided data separated into higher and lower ejection fraction subgroups. Five trials provided data separated into higher and lower New York Heart Association (NYHA) class patient subgroups. For patients subcategorised by NYHA class, there was a non-significant difference in z-score (p=0.922) between patients with mild to moderate and severe heart failure. Similarly, subgrouping by left ventricular ejection fraction (LVEF) revealed no significant difference between z-scores (p=0.170). Both observations suggest no attenuation of benefit of ICD implantation in patients with higher NYHA class or lower LVEF. There is no evidence within the existing trial populations of a tendency for the relative risk reduction to be smaller in patients with severe heart failure. The prevailing assumption that severe heart failure patients are less likely to benefit from ICD therapy must be questioned.


[Nonsedative H1 antihistaminics].
Recent research provided evidence that effective H1-antihistaminic drugs need not exert a central and sedative action. Non-sedative H1-antihistaminics can aptly replace older combined preparations of classical H1-antihistaminics, motivated by an effort to weaken their sedative action by the concurrent administration of pharmaceutical preparations with a central stimulating action (e.g. Bromadryl F). The new group of non-sedative histamine H1-antagonists uses in a rational way changes of the physical and chemical properties of these substances or differences in their affinity to histamine H1-receptors in different areas to reduce the incidence of typical undesirable effects.


New approaches to the treatment of advanced prostate cancer.
Several presentations by attendees of the 11th International Prostate Cancer Update addressed recent advances in prostate cancer treatment. A study that examined whether a relationship exists between neuroendocrine (NE) cell differentiation and hormone-refractory prostate cancer (HRPC) concluded that the appearance of NE cells in prostatic carcinoma is an important phenomenon in the development of HRPC. Exisuland, a selective apoptotic antineoplastic drug, was compared to placebo in a recent study and was found to significantly inhibit the increase of prostate-specific antigen in patients who had undergone radical prostatectomy. A new dosing regimen for flutamide (500 mg daily) was found to have no significant differences from the currently recommended dose (250 mg every 8 hours); the new, single daily dose could meet with greater compliance and would reduce drug cost by 30%. The antiproliferative effect of vitamin D on prostatic carcinoma cells was discussed, along with the possible role of vitamin D supplementation during prostate cancer treatment. Finally, a presentation on hospice care acknowledged that referral for such care is unfortunately at times delayed by physicians, patients, and patients' families, leaving insufficient time for all the benefits of that stage of care to be realized.


Targeting nano drug delivery to cancer cells using tunable, multi-layer, silver-decorated gold nanorods.
Multifunctional nanoparticles have high potential as targeting delivery vehicles for cancer chemotherapy. In this study, silver-decorated gold nanorods (AuNR\Ag) have been successfully used to deliver specific, targeted chemotherapy against breast cancer (MCF7) and prostate carcinoma (PC3) cell lines. Doxorubicin, a commonly used chemotherapy, and anti-Epithelial cell adhesion molecule (anti-EpCAM) antibodies were covalently bonded to thiolated polyethylene glycol-coated AuNR\Ag, and the resultant system was used to deliver the drugs to cancer cells in vitro. Furthermore, these nanoparticles have a unique spectral signature by surface enhanced Raman spectroscopy (SERS), which enables reliable detection and monitoring of the distribution of these chemotherapy constructs inside cells. The development of interest in a plasmonic nano drugs system with unique spectroscopic signatures could result in a clinical approach to the precise targeting and visualization of cells and solid tumors while delivering molecules for the enhanced treatment of cancerous tumors.


The human plasma-metabolome: Reference values in 800 French healthy volunteers; impact of cholesterol, gender and age.
Metabolomic approaches are increasingly used to identify new disease biomarkers, yet normal values of many plasma metabolites remain poorly defined. The aim of this study was to define the "normal" metabolome in healthy volunteers. We included 800 French volunteers aged between 18 and 86, equally distributed according to sex, free of any medication and considered healthy on the basis of their medical history, clinical examination and standard laboratory tests. We quantified 185 plasma metabolites, including amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexose, using tandem mass spectrometry with the Biocrates AbsoluteIDQ p180 kit. Principal components analysis was applied to identify the main factors responsible for metabolome variability and orthogonal projection to latent structures analysis was employed to confirm the observed patterns and identify pattern-related metabolites. We established a plasma metabolite reference dataset for 144/185 metabolites. Total blood cholesterol, gender and age were identified as the principal factors explaining metabolome variability. High total blood cholesterol levels were associated with higher plasma sphingomyelins and phosphatidylcholines concentrations. Compared to women, men had higher concentrations of creatinine, branched-chain amino acids and lysophosphatidylcholines, and lower concentrations of sphingomyelins and phosphatidylcholines. Elderly healthy subjects had higher sphingomyelins and phosphatidylcholines plasma levels than young subjects. We established reference human metabolome values in a large and well-defined population of French healthy volunteers. This study provides an essential baseline for defining the "normal" metabolome and its main sources of variation.


Mechanism of reduction in alveolar-arterial PO2 difference by helium breathing in the exercising horse.
Previous work has shown that replacing N2 in air with He at the same inspired O2 fraction reduces the exercise-induced alveolar-arterial PO2 difference (AaPO2) in horses but has provided no mechanism explaining this effect. We sought to distinguish among possible causes by using the multiple inert gas elimination technique. Six horses were studied on a high-speed treadmill while they breathed either ambient air or normoxic He-O2. O2 uptake reached 138.0 ml.min-1.kg-1 and was not affected by He-O2. Temperature-corrected arterial PO2 was 76.7 Torr (air) and 86.9 Torr (He-O2) (P < 0.01). Corresponding AaPO2 was 22.3 and 15.9 Torr, respectively (P < 0.01). Mean AaPO2 predicted from ventilation-perfusion inequality did not change with He-O2 (12.7 Torr with air and 11.9 Torr with He-O2). Mean arterial PCO2 was 50.1 Torr with air and 44.1 Torr with He-O2 (P < 0.01); minute ventilation and tidal volume were correspondingly higher by 140 l/min and 1.0 liter, respectively, with He-O2. Pulmonary O2 diffusing capacity, cardiac output, and all ventilation-perfusion dispersion indexes did not change with He-O2. Intrapulmonary shunt was insignificant. Higher ventilation with He-O2 explained only approximately 4 Torr of the 10-Torr rise observed in arterial PO2. The remainder (and the corresponding fall in AaPO2) was due to more complete diffusion equilibration as a consequence of the higher minute ventilation and thus alveolar PO2, which reduced the average slope of the O2 dissociation curve, thereby increasing the ratio of diffusive to perfusive conductance.


Evaluation of electrostatic and hydrophobic effects on the interaction of mitochondrial signal sequences with phospholipid bilayers.
The information that directs a nuclear-coded protein to be imported into mitochondria resides in an N-terminal extension, called a signal sequence. The primary sequences of all known ones differ. The only common feature is their ability to theoretically form an amphiphilic, positively charged, alpha-helix. We previously showed that a short stable helical segment was required for a peptide to be functional in import [Wang, Y., & Weiner, H. (1993) J. Biol. Chem. 268, 4759-4765]. Here we investigate the interaction of three altered signal sequences with phospholipid membranes containing cardiolipin to ascertain the importance of electrostatic and hydrophobic interactions with the membrane. The three already described peptides were derivatives of the signal sequence from aldehyde dehydrogenase, which is composed of three segments, two helices separated by a linker. ANCN had the C-helix replaced by the N-helix of the signal sequence of cytochrome c oxidase subunit IV, ANCC had the C-terminal helix replaced by the C-terminal random coil of cytochrome oxidase subunit IV, and linker deleted had the linker region deleted. ANCC, which functioned poorly as a signal sequence, had a very low affinity for binding to the negatively charged membranes. In contrast, both ANCN and linker deleted showed a relatively high affinity for the membranes and were capable of functioning as a good leader sequence. It appears that linker deleted possessed a stronger hydrophobic effect with membranes while ANCN had a higher electrostatic interaction. On the basic of these studies, a model was proposed to describe the interaction of mitochondrial signal sequences with negatively charged phospholipid membranes involving electrostatic interaction for initial binding and hydrophobic interaction for insertion.(ABSTRACT TRUNCATED AT 250 WORDS)


Stabilization of Hypoxia-inducible Factor by DMOG Inhibits Development of Chronic Hypoxia-Induced Right Ventricular Remodeling.
One important determinant of longevity in congenital heart disease is right ventricular (RV) function, and this is especially true in cyanotic congenital heart disease. However, there is a paucity of data concerning right ventricular remodeling (RVR) in the setting of chronic hypoxia. Dimethyloxalylglycine (DMOG) is a competitive inhibitor of hypoxia-inducible factor (HIF)-hydroxylated prolyl hydroxylase and has been shown to play an important role against ischemia-reperfusion myocardial injury. We tested the hypothesis that DMOG prevents the development RVR after chronic hypoxia exposure. Rats were injected with saline or DMOG and exposed to room air or continued hypoxia for 4 weeks. In addition, we explored the response of myocardial erythropoietin and its receptor to hypoxic exposure. Treatment with DMOG attenuated myocardial fibrosis, apoptosis, and oxidative stress, which lead to enhanced RV contractile function. As an endpoint of HIF-dependent cardioprotection, a novel pathway in which nuclear factor kappa B links HIF-1 transcription was defined. This study supports a role for HIF-1 stabilizers in the treatment of RVR and brings into question the commonly held concept that RVR follows a linear relationship with increased RV afterload.


The puzzling incidence of testicular cancer in New Zealand: what can we learn?
Testicular germ cell tumour is the most common cancer to be diagnosed among young men. In New Zealand, we have observed some puzzling trends in the epidemiology of this disease. We have conducted a narrative review of available evidence regarding the puzzling epidemiology of testicular germ cell tumour in New Zealand and discussed the possible drivers of these trends. Whereas testicular cancer is most commonly a disease of White men, in New Zealand it is the indigenous Māori population that suffer by far the greatest rate of disease (age-adjusted relative risk: 1.80, 95% CI 1.58-2.05). Even more curiously, the rate of testicular germ cell tumour among Māori men aged 15-44 (28/100,000) is substantially greater than for Pacific Island men (9/100,000), a rare example of divergence between these two populations in terms of the incidence of any disease (cancer or otherwise). Our observations beg the following questions: first, why are rates of testicular germ cell tumour so much higher among Māori New Zealanders compared to the already high rates observed among European/Other New Zealanders? Second, why are rates of testicular germ cell tumour so completely divergent between Māori and Pacific New Zealanders, when these two groups typically move in parallel with respect to the incidence of given diseases? Finally, what might we learn about the factors that cause testicular germ cell tumour in general by answering these questions? This review examines the possible drivers of our observed disparity, discusses their feasibility, and highlights new work that is underway to further understand these drivers.


Results of a calcineurin-inhibitor-free immunosuppressive protocol in renal transplant recipients of expanded criteria deceased donors.
The increasing number of patients on waiting lists and the relatively stable organ procurement rate provide the groundwork for the use of expanded criteria deceased donors. While calcineurin-inhibitors (CNI) are excellent immunosuppressive drugs, their nephrotoxicity is largely responsible for the lack of improvement in long-term graft survival. The objective of this study was to analyze the results obtained with the use of a calcineurin inhibitor-free immunosuppressive protocol (polyclonal antibody induction, plus sirolimus, mycophenolate mofetil, and low doses of steroids) in terms of graft and patient survival as well as posttransplant clinical complications over 2 years. Under this immunosuppressive protocol, 78.04% of the patients completed the follow-up. A protocol biopsy was performed on 17 patients (53.1%) within 2 years posttransplant of which 82.31% were diagnosed as chronic allograph nephropathy grade I. The incidence of clinical complications was low and not significantly different from that reported with other immunosuppressive schemes. Death-censored graft survival was 95.12%. In conclusion, the use of a calcineurin inhibitor-free protocol in renal-transplant recipients of expanded criteria deceased donors was associated with excellent graft and patient survival rates and a low incidence of adverse events.


Thyroid dysfunction on the heart: clinical effects, prognostic impact and management strategies.
Thyroid hormones have a considerable influence on cardiac function and structure. There are direct and indirect effects of thyroid hormone on the cardiovascular system, which are prominent in both hypothyroidism and hyperthyroidism. In this review, we discuss how thyroid dysfunction impacts cardiovascular pathophysiology and the underlying molecular mechanisms.


A cytochrome C electron transfer switch modulated by heme ligation and isomerization of a peptidyl-prolyl bond.
Intermolecular electron transfer (ET) between hexaamineruthenium(II), a(6) Ru(2+) , and a K73H/K79A variant of iso-1-cytochrome c, iso-1-Cytc, is used to study conformational ET switches mediated by His73-heme ligation and cis to trans isomerization of the Ile75-Pro76 peptidyl-prolyl bond of iso-1-Cytc. The biomolecular rate constant for ET to the native state of K73H/K79A iso-1-Cytc is ∼270 mM(-1) s(-1) near neutral pH. The unimolecular conformational ET switches due to His73-heme ligation and the Ile75-Pro76 peptidyl-prolyl bond gate ET at rate constants of 5 to 10 s(-1) and 0.05 to 0.06 s(-1) . Thus, at 1 mM a(6) Ru(2+) , these conformational ET switches slow electron transfer by about 50- and 5000-fold, respectively. The conformational ET switches are populated between pH 5 and 7, providing a means of modulating ET in this redox protein over several orders of magnitude by simply changing pH. The conformationally-gated ET measurements are analyzed in the context of previous pH jump measurements on the His73-heme alkaline transition of K73H/K79A iso-1-Cytc. The ability to obtain microscopic rate constants with conformationally-gated ET measurements has allowed more precise determination of the pK(a) s of the three ionizable groups that mediate population of the His73-heme ET switch. We have also been able to show that the ionizable group with a pK(a) near 9 stabilizes the His73-heme conformer relative to the native state of iso-1-Cytc and that contrary to the conclusions from our pH jump studies, this ionization does not strongly affect the rate of the Ile75-Pro76 peptidyl-prolyl isomerization.


Cyanobacterial Toxic and Bioactive Peptides in Freshwater Bodies of Greece: Concentrations, Occurrence Patterns, and Implications for Human Health.
Cyanobacterial harmful algal blooms represent one of the most conspicuous waterborne microbial hazards in aquatic environments mostly due to the production of toxic secondary metabolites, mainly microcystins (MCs). Other bioactive peptides are frequently found in cyanobacterial blooms, yet their concentration and ecological relevance is still unknown. In this paper we studied the presence and concentration of cyanobacterial peptides (microcystins, anabaenopeptins, anabaenopeptilides) in 36 Greek freshwater bodies, using HPLC-DAD, ELISA, and PP1IA. Microcystins were found in more than 90% of the samples investigated, indicating that microcystin-producing strains seem to also occur in lakes without blooms. Microcystins MC-RR, MC-LR, and MC-YR were the main toxin constituents of the bloom samples. Anabaenopeptin A and B were predominant in some samples, whereas anabaenopeptolide 90A was the only peptide found in Lake Mikri Prespa. The intracellular concentrations of anabaenopeptins produced by cyanobacterial bloom populations are determined for the first time in this study; the high (>1000 µg·L(-1)) anabaenopeptin concentration found indicates there may be some impacts, at least on the ecology and the food web structure of the aquatic ecosystems. The maximum intracellular MC values measured in Lakes Kastoria and Pamvotis, exceeding 10,000 µg·L(-1), are among the highest reported.


Improved simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE II): protocol for a randomized evaluation.
The World Health Organization recommends rapid (≤ 7 days) or same-day initiation of antiretroviral treatment (ART) for HIV-positive patients. South Africa adopted this recommendation in 2017, but multiple clinic visits, long waiting times, and delays for laboratory tests remain common. Streamlined approaches to same-day initiation that allow the majority of patients to start ART immediately, while ensuring that patients who do require additional services receive them, are needed to achieve national and international treatment program goals. The SLATE II (Simplified Algorithm for Treatment Eligibility) study is an individually randomized evaluation of a clinical algorithm to reliably determine a patient's eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. It differs from the earlier SLATE I study in management of patients with symptoms of tuberculosis (under SLATE II these patients may be started on ART immediately) and other criteria for immediate initiation. SLATE II will randomize (1:1) 600 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa. Patients randomized to the standard arm will receive standard-of-care ART initiation from clinic staff. Patients randomized to the intervention arm will be administered a symptom report, medical history, brief physical exam, and readiness assessment. Symptomatic patients will also have a tuberculosis (TB) module with lipoarabinomannan antigen of mycobacteria test. Patients who have satisfactory results for all four components will be dispensed antiretrovirals (ARVs) immediately, at the same clinic visit. Patients who have any negative results will be referred for further investigation, care, counseling, tests, or other services prior to being dispensed ARVs. Follow-up will be by passive medical record review. The primary outcomes will be ART initiation in ≤ 7 days and retention in care 8 months after study enrollment. SLATE II improves upon the SLATE I study by reducing the number of reasons for delaying ART initiation and allowing more patients with TB symptoms to start ART on the day of diagnosis. If successful, SLATE II will provide a simple and streamlined approach that can readily be adopted in other settings without investment in additional technology. ClinicalTrials.gov, NCT03315013 . Registered on 19 October 2017.


A 5-structured visits multidisciplinary clinical care approach to optimize the care of patients with type 2 diabetes: a pilot study.
Multidisciplinary coordinated care has been associated with improvement of diabetes care. This is a retrospective cohort analysis aimed to assess the effect of application of the five-structured visits Multi-disciplinary Clinical Care Approach (FMCA) on each of T2DM control, complications and comorbidities. The patients' records were assessed for one year of regular diabetes care followed with a year after implementation of FMCA for patients attending the diabetes clinic at Zulekha hospital. The patients were divided according to HbA1c (cutoff 7%) at the end of the FMCA year of follow-up into a group of controlled and another group of uncontrolled diabetes designated CDM and UCDM, respectively. 49% of patients were males and the mean age was 44.22 years. HbA1c levels, LDL and urinary albumin/creatinine ratio (UACR) showed a marked decrease among the patients after implementation of FMCA (P = 0.02, P = 0.04, P = 0.003, respectively). Compared with an increase in the atherosclerotic cardiovascular risk score (ASCVD) during the regular period, exposure to FMCA significantly decreased the cardiovascular risk score (0.17%, 11.41%, P = 0.001, P = 0.001, respectively). A self-management score was significantly higher in CDM patients. After a multivariate regression analysis of factors affecting DM control, we detected that baseline HbA1c, UACR, self-management score and hospital admission rate were the most important factors to predict diabetes control. The implementation of FMCA has shown a significant improvement in clinical and humanistic aspects of individuals with T2DM with a better outcome, more control and less complications.


Inflammation: predictive factor for negative evolution of prostate diseases.
The most frequent prostate diseases depending on age are prostatitis in young men, benign prostate hypertrophy in men over 50 years old, and prostate cancer (PCa) in elderly patients. The purpose of our study is to evaluate the role of inflammation in the progression of prostate diseases. We used clinical and paraclinical techniques for the positive diagnosis [serum prostate-specific antigen (PSA) determination, we performed transrectal ultrasound to asses the prostate volume and prostate biopsy or transurethral resection of the prostate, where it was imposed]. The prostate tissue specimens were analyzed histopathologically and immunohistochemically. Our results show that PCa patients with higher inflammation rates had a higher Gleason score in both the castration-resistant prostate cancer (CRPC) group and the castration-sensitive group. We have noticed that patients with high inflammation grade also had a much higher International Prostate Symptom Score (IPSS). In conclusion, we can say that in our study, inflammation played an important role in the evolution of benign and malignant prostate diseases; its presence has influenced directly the severity of symptoms, and the aggressiveness of the diseases.


[Echographic aspects of renal tuberculosis].
In this study the Authors examine the utility of the ultrasonographic investigation in the preoperative evaluation of 22 patients submitted to nephrectomy for tubercular lesions, comparing the informations obtained from this procedure with the histologic report. The renal ultrasonography execute with a Toshiba 3.5 Mhz probe, has been utilized to value morphology, volume, parenchymal echostructure and hydronephrosis. According to the Author's series, the ultrasonography has shown a 100% sensitivity permitting to well value the presence of parenchymal lesions and hydronephrosis. As regards the tubercular renal injuries the ultrasonography is non-specific because it does not allow to have pathognomonic images. The results obtained from the U.S. are overlapping to the Results Related from the literature for abdominal CT. The Authors argue that U.S., rapid and economical investigation is an efficient complement to the urography for an exhaustive preoperative evaluation of patients suffering from renal Tuberculosis.


A STUDY OF GRANULES AND OTHER CHANGES IN PHASE-CONTRAST APPEARANCE PRODUCED BY CHEMOTHERAPEUTIC AGENTS IN TRYPANOSOMES.
The morphological changes produced by four series of organic trypanocidal drugs have been studied by quantitative and by qualitative methods using phase-contrast and fluorescence microscopy. Basic drugs were absorbed rapidly into the region of the kinetoplast; acidic drugs did not affect this region. Faint granules, which were present in some trypanosomes before the administration of drugs, absorbed the drugs and increased in contrast relative to the cytoplasm. Hydroxystilbamidine, quinapyramine, related compounds, and possibly also suramin produced additional granules which did not contain drug. These additional granules are similar to the granules (volutin granules) which occur in trypanosome infections (not treated with drugs) when trypanosomes are about to be cleared from the blood. Homidium did not produce additional granules.


Asymmetric epigenetic modification and elimination of rDNA sequences by polyploidization in wheat.
rRNA genes consist of long tandem repeats clustered on chromosomes, and their products are important functional components of the ribosome. In common wheat (Triticum aestivum), rDNA loci from the A and D genomes were largely lost during the evolutionary process. This biased DNA elimination may be related to asymmetric transcription and epigenetic modifications caused by the polyploid formation. Here, we observed both sets of parental nucleolus organizing regions (NORs) were expressed after hybridization, but asymmetric silencing of one parental NOR was immediately induced by chromosome doubling, and reversing the ploidy status could not reactivate silenced NORs. Furthermore, increased CHG and CHH DNA methylation on promoters was accompanied by asymmetric silencing of NORs. Enrichment of H3K27me3 and H3K9me2 modifications was also observed to be a direct response to increased DNA methylation and transcriptional inactivation of NOR loci. Both A and D genome NOR loci with these modifications started to disappear in the S4 generation and were completely eliminated by the S7 generation in synthetic tetraploid wheat. Our results indicated that asymmetric epigenetic modification and elimination of rDNA sequences between different donor genomes may lead to stable allopolyploid wheat with increased differentiation and diversity.


Veterans Affairs' Whole Health System of Care for Transitioning Service Members and Veterans.
The Department of Veterans Affairs (VA) has launched an organization-wide transformation to a Whole Health System of Care that will ideally begin at the time of transition from active duty through the end of a Veteran's life. A brief history and overview of the Whole Health approach are provided along with selected evaluation results and planned initial actions as a result of the Total Force Fitness-Whole Health Summit held in March 2022. More work is required to strengthen the natural linkages between the Department of Defense's Total Force Fitness and Veterans Affairs' Whole Health approach to care. The Total Force Fitness-Whole Health collaboration is a model of whole-person care for the nation.


The effect of a smartphone-based coronary heart disease prevention (SBCHDP) programme on awareness and knowledge of CHD, stress, and cardiac-related lifestyle behaviours among the working population in Singapore: a pilot randomised controlled trial.
Coronary heart disease (CHD) is the most prevalent type of cardiac disease among adults worldwide, including those in Singapore. Most of its risk factors, such as smoking, physical inactivity and high blood pressure, are preventable. mHealth has improved in the last decade, showing promising results in chronic disease prevention and health promotion worldwide. Our aim was to develop and examine the effect of a 4-week Smartphone-Based Coronary Heart Disease Prevention (SBCHDP) programme in improving awareness and knowledge of CHD, perceived stress as well as cardiac-related lifestyle behaviours in the working population of Singapore. The smartphone app "Care4Heart" was developed as the main component of the programme. App content was reviewed and validated by a panel of experts, including two cardiologists and two experienced cardiology-trained nurses. A pilot randomised controlled trial was conducted. Eighty working people were recruited and randomised to either the intervention group (n = 40) or the control group (n = 40). The intervention group underwent a 4-week SBCHDP programme, whereas the control group were offered health promotion websites only. The participants' CHD knowledge, perceived stress and behavioural risk factors were measured at baseline and on the 4th week using the Heart Disease Fact Questionnaire-2, Perceived Stress Scale, and Behavioural Risk Factor Surveillance System. After the SBCHDP programme, participants in the intervention group had a better awareness of CHD being the second leading cause of death in Singapore (X 2 = 6.486, p = 0.039), a better overall CHD knowledge level (t = 3.171, p = 0.002), and better behaviour concerning blood cholesterol control (X 2 = 4.54, p = 0.033) than participants in the control group. This pilot study partially confirmed the positive effects of the SBCHDP programme in improving awareness and knowledge of CHD among the working population. Due to the small sample size and short follow-up period, this study was underpowered to detect significant differences between groups. A full-scale longitudinal study is required in the future to confirm the effectiveness of the SBCHDP programme.


Regional Adiposity and Risk of Heart Failure and Mortality: The Jackson Heart Study.
Background Visceral adipose tissue (VAT) is associated with incident heart failure (HF) and HF with preserved ejection fraction, yet it is unknown how pericardial and abdominal adiposity affect HF and mortality risks in Black individuals. We examined the associations of pericardial adipose tissue (PAT), VAT, and subcutaneous adipose tissue (SAT) with incident HF hospitalization and all-cause mortality in a large community cohort of Black participants. Methods and Results Among the 2882 Jackson Heart Study Exam 2 participants without prevalent HF who underwent body computed tomography, we used Cox proportional hazards models to examine associations between computed tomography-derived regional adiposity and incident HF hospitalization and all-cause mortality. Fully adjusted models included demographics and cardiovascular disease risk factors. Median follow-up was 10.6 years among participants with available VAT (n=2844), SAT (n=2843), and PAT (n=1386). Fully adjusted hazard ratios (95% CIs) of distinct computed tomography-derived adiposity measures (PAT per 10 cm3, VAT or SAT per 100 cm3) were as follows: for incident HF, PAT 1.08 (95% CI, 1.02-1.14) and VAT 1.04 (95% CI, 1.01-1.08); for HF with preserved ejection fraction, PAT 1.13 (95% CI, 1.04-1.21) and VAT 1.07 (95% CI, 1.01-1.13); for mortality, PAT 1.07 (95% CI, 1.03-1.12) and VAT 1.01 (95% CI, 0.98-1.04). SAT was not associated with either outcome. Conclusions High PAT and VAT, but not SAT, were associated with incident HF and HF with preserved ejection fraction, and only PAT was associated with mortality in the fully adjusted models in a longitudinal community cohort of Black participants. Future studies may help understand whether changes in regional adiposity improves HF, particularly HF with preserved ejection fraction, risk predictions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005485.


[Urethral diverticula in women].
We present results of 3 female patients with periurethral abscesses and 1 patient with urethral diverticle, who were hospitalized in our department. The aim of this study is to draw attention on incidence in women including those without urological sympatology. (Fig. 2, Ref. 5.)


Amyotrophic lateral sclerosis transcriptomics reveals immunological effects of low-dose interleukin-2.
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease causing upper and lower motor neuron loss and currently no effective disease-modifying treatment is available. A pathological feature of this disease is neuroinflammation, a mechanism which involves both CNS-resident and peripheral immune system cells. Regulatory T-cells are immune-suppressive agents known to be dramatically and progressively decreased in patients with amyotrophic lateral sclerosis. Low-dose interleukin-2 promotes regulatory T-cell expansion and was proposed as an immune-modulatory strategy for this disease. A randomized placebo-controlled pilot phase-II clinical trial called Immuno-Modulation in Amyotrophic Lateral Sclerosis was carried out to test safety and activity of low-dose interleukin-2 in 36 amyotrophic lateral sclerosis patients (NCT02059759). Participants were randomized to 1MIU, 2MIU-low-dose interleukin-2 or placebo and underwent one injection daily for 5 days every 28 days for three cycles. In this report, we describe the results of microarray gene expression profiling of trial participants' leukocyte population. We identified a dose-dependent increase in regulatory T-cell markers at the end of the treatment period. Longitudinal analysis revealed an alteration and inhibition of inflammatory pathways occurring promptly at the end of the first treatment cycle. These responses are less pronounced following the end of the third treatment cycle, although an activation of immune-regulatory pathways, involving regulatory T-cells and T helper 2 cells, was evident only after the last cycle. This indicates a cumulative effect of repeated low-dose interleukin-2 administration on regulatory T-cells. Our analysis suggested the existence of inter-individual variation amongst trial participants and we therefore classified patients into low, moderate and high-regulatory T-cell-responders. NanoString profiling revealed substantial baseline differences between participant immunological transcript expression profiles with the least responsive patients showing a more inflammatory-prone phenotype at the beginning of the trial. Finally, we identified two genes in which pre-treatment expression levels correlated with the magnitude of drug responsiveness. Therefore, we proposed a two-biomarker based regression model able to predict patient regulatory T-cell-response to low-dose interleukin-2. These findings and the application of this methodology could be particularly relevant for future precision medicine approaches to treat amyotrophic lateral sclerosis.


Single nucleotide polymorphisms typing of Mycobacterium leprae reveals focal transmission of leprosy in high endemic regions of India.
Earlier studies indicate that genotyping of Mycobaterium leprae based on single-nucleotide polymorphisms (SNPs) is useful for analysis of the global spread of leprosy. In the present study, we investigated the diversity of M. leprae at eight SNP loci using 180 clinical isolates obtained from patients with leprosy residing mainly in Delhi and Purulia (West Bengal) regions. It was observed that the frequency of SNP type 1 and subtype D was most predominant in the Indian population. Further, the SNP type 2 subtype E was noted only from East Delhi region and SNP type 2 subtype G was noted only from the nearby areas of Hoogly district of West Bengal. These results indicate the occurrence of focal transmission of M. leprae infection and demonstrate that analysis by SNP typing has great potential to help researchers in understanding the transmission of M. leprae infection in the community.


Advances in image enhancement in colonoscopy for detection of adenomas.
High-quality colonoscopy is mandatory to prevent adenoma recurrence and colorectal cancer. In the past few years, technical advances have been developed with the purpose of improving adenoma detection rate (ADR), one of the most important validated colonoscopy quality benchmarks. Several techniques or devices are used to optimize visualization: observation techniques; add-on devices; auxiliary imaging devices; colonoscopes with increased field of view; and colonoscopes with an integrated inflatable reusable balloon. Image-enhanced endoscopy (IEE) facilitates the detection and characterization of polyps and especially nonpolypoid colorectal neoplasms. Indigo carmine is the most frequently used dye in colonoscopy as it deposits in depressed areas, improving detection of flat and depressed lesions. Virtual chromoendoscopy has emerged as an effective contrast enhancement technology without the limitation of preparing dyes and applying them through the colonoscope working channel. Narrow-band imaging (NBI) enhances the capillary pattern and surface of the mucosa using optical filters, and second-generation NBI provides a twofold brighter image than the previous system, yielding promising ADR results. Moreover, a second-generation blue laser imaging system, LASEREO, has been reported to improve not only polyp detection rate but also ADR, becoming a promising IEE modality. Herein, we describe technical advances in colonoscopy imaging and their effect on ADR.


[Isoflavones and calcified tissues].
The data about osteotropic action of isoflavones are presented in this review. Isoflavones are the compounds of phytoestrogenes group--hormone-like bioregulators of plant origin. Animal experiments as well as bone tissue and bone cells cultures investigations demonstrate anabolic effect of isoflavones on bone metabolism. Isoflavones prevent bone loss in ovariectomized animals. They inhibit bone resorbition and enhance bone formation. Because of this natural and synthetic isoflavones hold great promise in the prevention and treatment of osteoporosis. These compounds may also be effective in preventing bone loss associated with hypodynamia or immobility, ovariectomy or postmenopausal hypoestrogenia, chronic corticosteroid use, renal osteodystrophy, hyperparathyroidism and other metabolic disorders affecting the calcified tissues, including alveolar bone loss in periodontal disease as well as dental hard tissues destruction.


Association of Implantable Cardioverter Defibrillators With Survival in Patients With and Without Improved Ejection Fraction: Secondary Analysis of the Sudden Cardiac Death in Heart Failure Trial.
Improvement in left ventricular ejection fraction (EF) to >35% occurs in many patients with reduced EF at baseline. To our knowledge, whether implantable cardioverter defibrillator (ICD) therapy improves survival for these patients is unknown. To examine the efficacy of ICD therapy in reducing risk of all-cause mortality and sudden cardiac death among patients with an EF ≤35% at baseline, with or without an improvement in EF to >35% during follow-up. This retrospective analysis examined data collected in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which randomly assigned 2521 patients to placebo, amiodarone, or ICD between 1997 and 2001. A subset of 1902 participants (75.4%) of the SCD-HeFT had a repeated assessment of EF a mean (SD) of 13.5 (6) months after randomization. We stratified these patients by EF ≤35% and >35% based on the first repeated EF measurement after randomization and compared all-cause mortality in 649 patients randomized to placebo vs 624 patients randomized to ICD. Follow-up started with the repeated EF assessment. Analysis was performed between January 2016 and July 2016. Implantable cardioverter-defibrillator therapy. All-cause mortality and sudden cardiac death. Of the included 1273 patients, the mean (SD) age was 59 (12) years, and 977 (76.7%) were male and 1009 (79.3%) were white. Repeated EF was >35% in 186 participants (29.8%) randomized to ICD and 185 participants (28.5%) randomized to placebo. During a median follow-up of 30 months, the all-cause mortality rate was lower in the ICD vs placebo group, both in patients whose EF remained ≤35% (7.7 vs 10.7 per 100 person-year follow-up) and in those whose EF improved to >35% (2.6 vs 4.5 per 100 person-year follow-up). Compared with placebo, the adjusted hazard ratio for the effect of ICD on mortality was 0.64 (95% CI, 0.48-0.85) in patients with a repeated EF of ≤35% and 0.62 (95% CI, 0.29-1.30) in those with a repeated EF >35%. There was no interaction between treatment assignment and repeated EF for predicting mortality. Among participants in the SCD-HeFT who had a repeated EF assessment during the course of follow-up, those who had an improvement in EF to >35% accrued a similar relative reduction in mortality with ICD therapy as those whose EF remained ≤35%. Prospective randomized clinical trials are needed to test ICD efficacy in patients with an EF >35%. clinicaltrials.gov Identifier: NCT01114269.


[An update of Bassini's operation for the treatment of inguinal hernia].
Although the Bassini hernioplasty has been criticized, particularly by North American surgeons because of a high incidence of recurrence, among the techniques used for inguinal hernia repair, the Bassini method, in authors' opinion, is still the best if correctly performed. In fact, the transversalis fascia division is fundamental to obtain a better mobilization of the triple layer (transversalis fascia, transversus abdominis, internal oblique) which can approach the inguinal ligament without tension. Hernia repair is achieved by suturing this layer to the pubic tubercle and inguinal ligament with separated stitches.


Three dimensional architecture of lymphatic vessels in the tongue.
We have three-dimensionally reconstructed the lymphatic architecture of the rabbit tongue using a computer graphic three-dimensional reconstruction method together with histochemically stained serial cryo-sections. Three collecting lymphatic vessels lying in an anteroposterior orientation were identified in the tongue body. A superior longitudinal muscle accompanying collecting lymphatic (SLCL) that lies in the border between superior longitudinal muscle and transverse muscle was identified in this study, in addition to collecting lymphatics in the lingual septum (LSCL) and deep lingual artery accompanying collecting lymphatics (DLCL) that we reported previously. The vertical muscle accompanying collecting lymphatics (VCL) and the transverse muscle accompanying collecting lymphatics (TCL) were also identified as collecting lymphatics that joined the above three collecting lymphatics. Specific regional lymph flow was identified for each collecting lymphatic. A transverse right/left cross flow was identified for the LSCL, while the SLCL served the upper 1/3 of the tongue and the DLCL served the lower 2/3 of the tongue. Each collecting lymphatic that accompanied the internal lingual muscles joined to the SLCL, DLCL and LSCL, and were derived from blind-ended lymphatic capillaries that ran in the endomysium. Internal lingual muscle accompanying collecting lymphatics joined each other in the endomysium, and their blind-ended lymphatic capillaries had no branches.


Postureteroscopic lesion scale: a new management modified organ injury scale--evaluation in 435 ureteroscopic patients.
Objective parameters for the classification of ureteral injuries and resulting indications for ureteral stent placement after ureteroscopy are lacking. We hereby present a new classification system including proof of interrater reliability and validation of recommendations for postoperative ureteral stent placement. The Postureteroscopic Lesion Scale (PULS) was applied in 435 patients undergoing ureteroscopy. Interrater reliability between three surgeons (junior resident, senior resident, and specialist) was evaluated in 112 patients. Postoperative ureteral stent placement was performed according to PULS. For follow-up with ultrasonography, we assumed hydronephrosis to be an indirect sign for significant postoperative ureteral obstruction. No ureteral lesion was seen in 46.2% of patients (grade 0). A grade 1, 2, or 3 lesion was seen in 30.8%, 19.1%, and 3.9% of patients, respectively. No grade 4 or 5 lesions were observed in our series. Interrater reliability was high (Kendall W=0.91; mean Spearman Rho=0.86). This was particularly true between senior resident and specialist (Rho=0.95), compared with junior resident and senior resident or specialist (Rho=0.83, Rho=0.79, respectively). All patients with documented lesions had a Double-J stent placed. Indwelling time varied according to PULS. Results of a postoperative ultrasonographic follow-up could be obtained in 95.6% of cases. No patient showed clinical or sonographic signs of upper urinary tract obstruction. According to these preliminary data for the clinical application of PULS, interrater reliability is high. Standardized empiric recommendations for the use and duration of postoperative stent placement after ureteroscopy might be useful in guiding urologists in this conversely discussed issue, ultimately preventing ureteral strictures as a late complication of ureteroscopy. These will have to be confirmed, however, by controlled trials in the future.


Antifungal susceptibilities of Candida spp. isolated from blood in Spain and Argentina, 1996-1999.
The aim of this study was to identify retrospectively trends in species distribution and susceptibility patterns of Candida species causing bloodstream infections in 99 medical centres (55 in Spain and 44 in Argentina) from 1996 to 1999. A total of 744 Candida isolates were sent to the mycology reference laboratories during the study period (514 to the Spanish laboratory and 230 to the Argentinian laboratory). Candida non-albicans strains caused more episodes of fungaemia than Candida albicans isolates in both Spain and Argentina. C. albicans was isolated in 30.2% (155/514) and 40.9% (94/230) of episodes in Spain and in Argentina, respectively. In addition, Candida parapsilosis was the second most commonly isolated pathogen (36.4%). Candida tropicalis caused 13.7% of infections and Candida glabrata 7.4%. The amphotericin B MIC was <or=1 mg/L for 97.5% of isolates, and 8.3% of strains had decreased susceptibility to flucytosine. Regarding susceptibility to azole agents, 9.9% (74/744) and 21.9% (163/744) exhibited decreased susceptibility to fluconazole and itraconazole, respectively. For Candida species, some marked differences were found between countries, and decreased susceptibility to azole agents was detected significantly more frequently (P < 0.05) among Argentinian isolates of C. albicans, C. parapsilosis and C. tropicalis. These findings reinforced the need for continued surveillance programmes to analyse the factors that may have an influence on candidaemia incidence. Susceptibility patterns were obtained by means of the proposed reference procedure for antifungal susceptibility testing of the European Committee on Antibiotic Susceptibility Testing (EUCAST). Excellent interlaboratory agreement was achieved for MICs for quality control strains noted in Spain and in Argentina (intraclass correlation coefficient of 0.97), indicating that the EUCAST procedure is a reliable methodology for susceptibility testing.


Using self-efficacy to predict weight loss among young adults.
Many healthcare professionals support the idea that weight control and healthy eating should be emphasized early in a person's life to prevent obesity during middle and older adulthood. Unfortunately, although many weight loss programs are available to consumers, few are successful. Recently, constructs of behavioral theories have been integrated into weight loss programs and used to promote changes in health behaviors. In this study, methods used to increase self-efficacy for weight loss were incorporated into a 12-week program designed for weight loss promotion in young adults. Results found that as self-efficacy improved, eating habits improved and weight loss was greater. This study supports the hypothesis that using behavioral techniques to improve self-efficacy can be effective in weight loss promotion and can produce positive outcomes.


Prenatal Diagnosis of Vesicorectal Fistula.
Anorectal malformations are a rare condition difficult to diagnose in the prenatal period. It can be suspected if distal bowel appears dilated in the first-trimester ultrasound or if intraluminal echogenic foci are detected during the second-trimester scan. We report a case with these ultrasound signs (dilated sigmoid at the first trimester and intraluminal echogenic calcifications at the second trimester), in which a vesicorectal fistula image was obtained. This is the first published prenatal image of a vesicorectal fistula.


How much influence do women in Sweden have on caesarean section? A follow-up study of women's preferences in early pregnancy.
to investigate factors associated with having a caesarean section, with special emphasis on women's preferences in early pregnancy. a cohort study using data from questionnaires in early pregnancy and 2 months after childbirth, and data from the Swedish Medical Birth Register. women were recruited from 97% of all antenatal clinics in Sweden at their booking visit during 3 weeks between 1999 and 2000, and followed up 2 months after birth. a total of 2878 Swedish-speaking women were included in the study (87% of those who consented to participate and 63% of all women eligible for the study). Of 236 women who wished to have their babies delivered by caesarean section when asked in early pregnancy, 30.5% subsequently had an elective caesarean section and 14.8% an emergency caesarean section. The logistic regression analyses showed that, a preference for caesarean section in early pregnancy (odds ratio [OR] 9.63, 95% confidence interval [CI] 5.94-15.59), a medical diagnosis (OR 9.03, 95% CI 5.68-14.34), age (OR 1.08, 95% CI 1.03-1.13), parity (OR 0.58, 95% CI 0.37-0.91), a previous elective caesarean section (OR 15.11, 95% CI 6.83-33.41) and a previous emergency caesarean section (OR 18.29, 95% CI 10.00-33.44) was associated with having an elective caesarean section. Having an emergency caesarean section was associated with a preference for a caesarean section (OR 2.59, 95% 1.61 to 4.18), a medical diagnosis (OR 4.12, 95% CI 2.91-5.88), age (OR 1.08, 95% CI 1.05-1.12), primiparity (OR 3.34, 95% CI 1.78-6.27), a previous emergency caesarean section (OR 10.69, 95% CI 6.03-18.94), and a previous elective caesarean section (OR 7.21, 95% CI 2.90-17.92). a woman's own preference about caesarean section was associated with the subsequent mode of delivery. Asking women about their preference regarding mode of delivery in early pregnancy may increase the opportunity to provide adequate support and possibly also to reduce the caesarean section rate.


Diallyl trisulfides, a natural histone deacetylase inhibitor, attenuate HIF-1α synthesis, and decreases breast cancer metastasis.
Intratumoral hypoxia promotes the distant metastasis of cancer subclones. The clinical expression level of hypoxia-inducible factor-1α (HIF-1α) reflects the prognosis of a variety of cancers, especially breast cancer. Histone deacetylase (HDAC) inhibitors can target HIF-1α protein due to von Hippel-Lindau (VHL) protein-dependent degradation. Dietary organosulfur compounds, such as those in garlic, have been reported as HDAC inhibitors. The effects of diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS) on the ratio of firefly/Renilla luciferase activity in hypoxic MDA-MB-231 cells were determined. The mRNA expressions of HIF-1α target genes ANGPTL4, LOXL4, and LOX in hypoxic MDA-MB-231 cells were significantly down-regulated by DATS. DATS attenuated the metastatic potential of MDA-MB-231 cells in hypoxia-induced embryonic zebrafish, xenograft, and orthotopic tumors. Endothelial cell-cancer cell adhesion, wound healing, transwell, and tube formation assays showed that DATS dose-dependently inhibited the migration and angiogenesis of MDA-MB-231 cells in vitro. The expressions of L1CAM, VEGF-A, and EMT-related proteins (Slug, Snail, MMP-2) were inhibited by DATS. DATS dose-dependently inhibited HIF-1α transcriptional activity and hypoxia-induced hematogenous metastasis of MDA-MB-231 cells. It reduced the protein expression of HIF-1α, which did not involve inhibition of HIF-1α mRNA expression or ubiquitin proteasome degradation. Efficient inhibition of HIF-1α expression was required for DATS to resist breast cancer.


Reliability of ultrasound-guided fine-needle biopsy of pancreatic masses.
Fine-needle aspiration biopsy (FNB) was performed with ultrasound guidance in 79 patients in whom sonography had revealed a mass suggesting pancreatic malignancy. The final diagnosis (surgery, autopsy and clinical course) in 69 of these 79 patients was a malignancy closely related to the pancreas while in the remaining 10 patients benign disease was confirmed. A correct diagnosis of malignancy was attained by FNB in 59 of the 69 patients with a malignant tumour while in 10 it failed to confirm the diagnosis. FNB yielded a true negative result in 10 patients with benign disease. The accuracy of sonographically guided FNB in the present investigation was 87 per cent. Ultrasound-guided fine-needle biopsy is considered the method of choice for further evaluation of pancreatic masses.


Expert Outpatient Burn Care in the Home Through Mobile Health Technology.
Access to care for pediatric burns remsains a major public health problem in the United States. Telemedicine has an opportunity to improve access to care, but current models are expensive and inefficient. They have developed and pilot-tested the TeleBurn App, a novel smartphone application, to treat partial thickness burns while outpatient. The app allows the provision of expert clinical burn care directly in the patient's home through text and image messaging, video conferencing, and instructional videos. They retrospectively reviewed clinical outcomes and usability in pediatric partial thickness burn patients treated using the TeleBurn App compared with standard therapy alone. Standard therapy is considered to be face-to-face delivery of care. Burn wound care was provided to 32 patients via the app and 35 patients with standard therapy. Most (74%) patients offered the app, used it as their primary source of follow-up care. This group had no wound infections or unexpected returns to clinic or hospital. Both TeleBurn App and standard therapy groups had similar burn severity, age, and burn mechanism. Mean healing time was shorter in the app group (mean ± standard deviation: 11.6 ± 4.7 days versus standard therapy: 14.3 ± 5.4 [P = .03]) with fewer clinical encounters (0.93 ± 0.6 vs standard therapy: 3.3 ± 1.0 [P = .001]). Adherence with completion of therapy in patients using the app was 80 vs 64 per cent with standard therapy. They describe a functional, scalable mobile health application in clinical use in a pediatric burn program. Further prospective, randomized studies may validate this mobile health platform, improving access to expert burn care for a vulnerable population.


Trace Elements in Soils and Selected Agricultural Plants in the Tongling Mining Area of China.
The quality and safety of agricultural products from metal mining areas are of wide concern. In order to investigate the contents and health risks of trace elements in fruit vegetables planted in metal mining areas, 440 samples of fruit vegetables from 117 vegetable plots were collected from Tongling mining area. Trace element contents in fruit vegetables and soil were measured. The results indicated that the total concentration of trace elements in some of the soil samples exceeded the Grade II national standard in China. Transfer factor (TF) of Cd was the highest (8.360), followed by Zn, Cu, As, and Pb. Estimated daily intake (EDI) of the trace elements, except Cd, were generally below the maximum tolerable daily intake (MTDI). The target hazard quotient (THQ) of Zn for children was more than 1 in some vegetables, suggesting potential health hazards for child population. Total target hazard quotient (TTHQ) of Cu and Zn were also more than 1 through consumption of all vegetables, indicating significant health risks. For both adults and children, hazard index (HI) was more than 1 for the consumption of vegetables. The findings reveal the health risks associated with the consumption of trace elements through the intake of selected vegetables in the population of Tongling.


A comparative study of two antimicrobial/anti-inflammatory formulations in the treatment of canine otitis externa.
The efficacy and tolerability of a marbofloxacin-clotrimazole-dexamethasone otic suspension (MCD) was compared with a standard topical treatment using a phase III clinical trial protocol. In a total of 140 dogs with clinical signs of acute or subacute otitis externa, Staphylococcus, Pseudomonas, Enterobacteriaceae and Malassezia were isolated from samples taken at inclusion to identify the causative pathogen; a further sample was collected in the event of failure or relapse, and from dogs (at day 14) for which Pseudomonas species had been isolated at inclusion. One group received MCD (10 drops per affected ear) once daily and a second received Surolan (containing polymyxin B, miconazole and prednisolone) (5 drops per affected ear), twice daily. Each group received treatment for 7 or 14 days according to the clinical outcome on day 7. Efficacy and tolerability were evaluated on days 7, 14 and, if necessary, 28 for dogs treated for 14 days. The trial demonstrated equivalence of both treatments in terms of efficacy, with a cure rate of 58.3% for MCD and 41.2% for Surolan. Both medications were equally well tolerated by dogs, but MCD was superior in terms of pain relief, decrease in pus quantity and smell, response rate and investigator's assessment on day 14.


Relative pair dynamics in simple supercooled liquids: longitudinal contributions.
The pair dynamics of simulated argon samples is investigated at the melting (85 K), supercooled (55 K), and quenched (20 K) liquid states, and in the crystal (20 K) state. Tagged pairs, initially lying in a given shell, were divided into incoming and outgoing groups and followed along simulated trajectories. Over them, specific correlation functions deltaB(r(0);t), involving the pair separation vector projected along its initial value r(0) (longitudinal dynamics), have been evaluated. More or less pronounced oscillations are detected according to the temperature of the thermodynamic states (and, obviously, their solid or liquid nature); for each state, they depend on the initial pair distance r(0), too. The oscillations vanish after few picoseconds (fast dynamics) in the case of crystal, whereas in the supercooled liquid they decay towards a plateau, whose height increases with the temperature. It is shown that the power spectrum of deltaB(r(0);t) practically yields the same density of states (DOS) produced by the pair velocity correlation function. The deltaB(r(0);t) functions obtained from the argon crystal at 20 K produce DOS curves dominated by two main frequency contributions, at about 40 and 60 cm(-1) (Einstein and Debye frequency, respectively). Their shape is quite well reproduced by damped harmonic oscillator-like (DHO) functions vibrating at that frequencies. In liquid states, the deltaB(r(0);t) plateau, that forms after the fast DHO dynamics, accounts for the system diffusivity. The relaxation towards the plateau is modeled by an exponential function whose decay time is comparable with the average vibration period. Evidence that the liquid states conserve a certain memory of the vibrational modes of the crystal is obtained. In these states, the DHO functions at the Einstein and Debye frequencies plus an exponential function cannot reproduce the deltaB(r(0);t) shape. A pronounced shoulder, that forms around 0.5 ps, requires the contribution of a third DHO. In the DOS, it yields a band centered below 20 cm(-1) that produces low frequency DOS excess in comparison with the DOS of the crystal. This contribution is present in liquid and supercooled high temperature states and survives near the temperature of the glass transition whereas the diffusion practically vanishes.


Identification of sensitizing diethyleneglycol maleate in a two-component polyester cement.
Unsaturated polyester (UP) cement caused allergic contact dermatitis in car repair work. The resin was a condensate of polyols and maleic anhydride with reactive solvent, auxiliary substances, and inorganic reinforcement substances. To identify the causative chemicals, the cement was tested on a sensitized patient. For analysis, samples of the resin were eluted with acetone and eluted with hexane to precipitate inorganic material and large polyester molecules. The eluate was evaporated. The remainder, dissolved in acetone, was separated into fractions on silica plates by thin layer chromatography (TLC). On the developed (hexane/chloroform, 15/85) plates, 20 bands were obtained under UV-light at 254 nm. Samples of the bands were scraped and used for patch testing. The scraping at a retention factor (Rf) of 0.24 caused a skin reaction. The bands at this retention were removed from six plates, combined, eluted with acetone and purified again by TLC. The purified fraction mixed in petrolatum in the dilution series was used for conclusive patch testing on the patient. An allergic reaction was induced at down to 0.003% wt/wt. According to MS and IR analyses, the isolated compound was diethyleneglycol maleate (DEGM, MW204). In addition to the resin part, the sanding dust also contained this monomer.


Adipophilin-enriched domains in the ER membrane are sites of lipid droplet biogenesis.
The prevailing hypothesis of lipid droplet biogenesis proposes that neutral lipids accumulate within the lipid bilayer of the ER membrane from where they are budded off, enclosed by a protein-bearing phospholipid monolayer originating from the cytoplasmic leaflet of the ER membrane. We have used a variety of methods to investigate the nature of the sites of ER-lipid-droplet association in order to gain new insights into the mechanism of lipid droplet formation and growth. The three-dimensional perspectives provided by freeze-fracture electron microscopy demonstrate unequivocally that at sites of close association, the lipid droplet is not situated within the ER membrane; rather, both ER membranes lie external to and follow the contour of the lipid droplet, enclosing it in a manner akin to an egg cup (the ER) holding an egg (the lipid droplet). Freeze-fracture cytochemistry demonstrates that the PAT family protein adipophilin is concentrated in prominent clusters in the cytoplasmic leaflet of the ER membrane closely apposed to the lipid droplet envelope. We identify these structures as sites at which lipids and adipophilin are transferred from ER membranes to lipid droplets. These findings call for a re-evaluation of the prevailing hypothesis of lipid droplet biogenesis.


Prostate specific antigen as tumor marker: relationship with histologic grading.
PSA is emerging as the best marker in oncology and had a profound impact on all aspects of prostate cancer care. From clinically suspected prostate tumor, 395 serum samples were taken out and estimated for serum PSA. Among elevated serum PSA, 98 were correlated with histologic findings. 42(42.8%) cases were BHP among 98 cases and 78.7% had serum PSA level within 10 ng/ml. 5 patients (5.1%) had PIN histologically, 3(60%) of which had PSA level upto 10 ng/ml and 2(40%) had serum PSA upto 20 ng/ml. 51(52%) were adenocarcinoma prostate of different grades and PSA level varies from less than 10 ng/ml to more than 50 ng/ml which almost correlates with the tumor grades.


Decomposition and long-lasting downregulation of extracellular matrix in perineuronal nets induced by focal cerebral ischemia in rats.
The upregulation of extracellular matrix components, especially chondroitin sulfate proteoglycans, after brain injury and stroke is known to accompany the glial reaction, forming repellent scars that hinder axonal growth and the reorganization of the injured neuronal networks. The extracellular matrix associated with perineuronal nets (PNs) in the primarily injured and remote regions has not yet been systematically analyzed. We use the model of permanent middle cerebral artery occlusion (MCAO) to investigate the acute and long-lasting consequences of ischemia for PNs, related to the damage of neurons and reactions of glial cells, in spontaneously hypertensive rats. Extracellular matrix components associated with PNs around cortical interneurons and neurons in thalamic nuclei were characterized 1, 7, 14, and 35 days after MCAO, using Wisteria floribunda agglutinin (WFA) staining and immunocytochemistry. The degradation of PNs in the infarct core was initiated by loss of WFA-binding matrix components, indicating the cleavage of glycosaminoglycan chains of chondroitin sulfate proteoglycans. Immunostaining showed the subsequent removal of proteoglycan core proteins within the extending microglia/macrophage invasion zone lasting for 2 weeks after MCAO. In the cortical periinfarct region, delineated by an astrocytic scar against the infarct core, the number of WFA-stained and proteoglycan core protein-immunoreactive PNs was permanently reduced. In the homolateral ventroposterior thalamus, the delayed decrease in perineuronal matrix was related to the distribution pattern of activated microglia and massive neuronal degeneration. It can be concluded from these results that complementary to the known upregulation of matrix components in the glial scar, deficits in the expression of the neuron-associated extracellular matrix develop in the periinfarct and remote regions. These deficits may contribute to the long-lasting functional impairments after stroke.


Different clinical presentations of Naxos disease and Carvajal syndrome: Case series from a single tertiary center and review of the literature.
Naxos disease is an autosomal recessive, inherited, cardiocutaneous disorder, characterized by arrhythmogenic right ventricular cardiomyopathy, woolly hair, and palmoplantar keratoderma. Carvajal syndrome is characterized by palmoplantar keratoderma, curly hair, dilated cardiomyopathy, especially on the left ventricle side, and early morbidity. The aim of this study was to evaluate the cutaneous and cardiac findings and genotype-phenotype relationship of six patients diagnosed with Naxos/Carvajal syndrome. A retrospective review of six cases diagnosed with Naxos/Carvajal syndrome at our institution from 2002 to 2012 was performed. Demographic data; presenting complaints; cutaneous and cardiac findings; electrocardiography, echocardiography, and genetic analysis results; and treatment data were obtained from patient files. The patient group was composed of 4 males and 2 females, ranging from 1.5 to 13 years, with a mean age 6.4 years. Typical cutaneous and hair findings were present in all patients. Two cases presented with ventricular tachycardia attack, and 2 cases presented with severe heart failure. Two cases had only cutaneous findings without cardiac involvement at diagnosis. An implantable cardioverter-defibrillator was implanted in one case due to ongoing recurrent ventricular tachycardia attacks despite various antiarrhythmic treatments. Three of the 6 patients died during the follow-up. For cases with woolly hair and palmoplantar keratoderma, the physician should provide a cardiac assessment, considering Naxos/Carvajal disease associated with cardiomyopathy. When an early diagnosis is made, the life expectancy may be increased by treatment of heart failure and arrhythmias; also, genetic counseling should be performed.


Classification of Human Milks Based on Their Trans 18:1 Fatty Acid Profile and Effect of Maternal Diet.
The diet of breastfeeding women influences the trans fatty acid (TFA) composition of the milk excreted. However, the effects associated to TFA are isomer-dependent and diverse TFA profiles may have different nutritional implications. The aim of this research was to evaluate whether certain TFA patterns in human milk fat can be used as indicators of TFA intake from different sources. Milk fat from 60 women were examined and classified based on their TFA profile and conjugated linoleic acid (CLA) contents by principal component analysis (PCA). The PCA of the data allowed the classification of the women into 3 groups depending on milk TFA content and profile. From the 60 subjects, 19 presented a TFA profile characteristic of ruminant products intake, 10 a typical TFA profile of industrial trans fats consumption and 31 a negligible trans content. Superimposed on this, 21 women presented high amounts of docosahexaenoic acid (22:6 n-3) which was related to fish intake. The present research overcome problems associated to heterogeneous groups in nutritional experiments by a statistical classification of lactating subjects based on the TFA composition of their milk. This classification could be extrapolated to other nutritional studies dealing with TFA analysis and samples of different nature as biological samples or foodstuffs.


Microcalorimetric determination of the thermostability of three hybrid (1-3,1-4)-beta-glucanases.
Thermodynamic parameters of the three hybrid (1-3,1-4)-beta-glucanases H(A12-M), H(A12-M) delta Y13, and H(A16-M) composed of short N-terminal regions derived from the Bacillus amyloliquefaciens enzyme and a C-terminal region of the homologous Bacillus macerans enzyme were determined in 2 mM sodium cacodylate pH 6.0, 1.5M guanidine hydrochloride, containing 1 mM CaCl2 or 1 mM EDTA. Melting of H(A12-M) delta Y13 and H(A16-M) in the presence of calcium ions is characterized by two subtransitions; only one transition is observed in the case of H(A12-M). In calcium-free buffer each of the three hybrid enzymes melts in one two-state transition. Transition temperatures Tm and molar enthalpy changes delta H are reduced in the absence of calcium ions but the reduction is much more pronounced for H(A12-M) delta Y13 and H(A16-M) than for the less thermostable enzyme H(A12-M).


Molecular mobility of elastin: effect of molecular architecture.
The thermal and dielectric properties of elastin and two soluble derivatives (kappa-elastin and derived elastin peptides from enzymatic elastolysis) were investigated in the freeze-dried state in a wide temperature range (from -180 to +220 degrees C). The glass transition of these amorphous proteins was studied by differential scanning calorimetry (DSC). The dielectric relaxations of both proteins were followed by thermally stimulated currents (TSC), an isochronal dielectric spectrometry running at variable temperature, analogous to a low-frequency spectroscopy (10(-3)-10(-2) Hz) and by dynamic dielectric spectroscopy (DDS), performed isothermally with the frequency varying from 10(-2) to 3 x 10(6) Hz. The combination of TSC and DDS experiments and the determination of the activation parameters of the relaxation times inform about the molecular mobility of the proteins, both in the glassy state and in the liquid state. Major differences between the relaxation behavior of elastin and its soluble derivatives have been discussed and correlated with the molecular architecture of the proteins.


Oxidative stress and motility impairment in the semen of fertile males.
The aim of the study was to determine the total oxidant status (TOS) and evaluate the influence of oxidative stress on sperm quality in fertile males. The study population consisted of 55 fertile males. Based on the seminal plasma TOS value, the study subjects were divided into the two subgroups: a group with a low (TOS-L) and a high (TOS-H) value. Comparing the TOS-H group with the TOS-L group, we found poorer sperm motility in the TOS-H group. We found lower total antioxidant capacity values and lower activity levels in the majority of the determined superoxide dismutase, glutathione peroxidase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase. Further, we found higher levels of copper and iron as well as lower levels of zinc in the TOS-H group. We observed lower medians of IL-2, 4, 6, 8 and INF-γ in the TOS-H group compared with the TOS-L group, whereas the medians of IL-1β, IL-10 and IL-12 were significantly higher. In fertile males, higher oxidative stress intensity was associated with poorer semen quality and decreased antioxidant capacity in semen. These negative effects might be a result of decreased activities of antioxidant enzymes and altered levels of trace metals and cytokines.


In situ analysis of doxorubicin uptake and cytotoxicity in a 3D culture model of human HT-1080 fibrosarcoma cells.
In solid tumors, chemotherapeutics must adequately diffuse through the extracellular compartment to achieve their cytotoxic effect. Using quantitative microspectrofluorometry, both Doxorubicin penetration through three-dimensional (3D) collagen I matrices and its subsequent intranuclear accumulation into HT-1080 cells cultured in this microenvironment were directly assessed. Evidence that collagen delayed the Doxorubicin penetration for 1 h is presented. During that period, drug concentrations were lower in the nuclei in 3D compared to 2D matrices. Anthracyclines were also found to exhibit similar cytotoxicity in 2D and 3D after long term incubation. In conclusion, in this 3D culture model, collagen type I matrices delayed the early distribution of low molecular weight therapeutics and failed to affect their long-term cytotoxic effects, as previously reported. This model may provide a rationale for avoiding the emergence of intrinsic chemoresistance in tissue.


The role of adhesion molecules in epithelial-T-cell interactions in thymus and skin.
Interaction of T lymphocytes with other cell types is important for normal T-cell development and function. Recently, a number of adhesion molecules important in T-cell interactions with other cell types have been defined. In this paper we review the role of two adhesion pathways, CD2/LFA-3 and LFA-1/ICAM-1, in T-cell interactions with epithelial cells of the thymus and skin. While thymic epithelium-T-cell interactions were mediated by both the LFA-1/ICAM-1 pathway and the CD2/LFA-3 pathway, epidermal-T-cell interactions were mediated primarily by the LFA-1/ICAM-1 pathway. Although ICAM-1 was not expressed in vivo on epidermal keratinocytes in normal skin, ICAM-1 was expressed by epidermal keratinocytes at the site of T-cell infiltration in inflammatory dermatitis. ICAM-1 was expressed in vivo on thymic epithelium. Both LFA-3 and ICAM-1 were expressed on epithelial cells of thymus and skin early on in fetal ontogeny. These antigen-independent adhesion molecules play an important role in the cell-cell interactions associated with T-cell differentiation and function.


Developmental response to cold stress in cranial morphology of Rattus: implications for the interpretation of climatic adaptation in fossil hominins.
Adaptation to climate occupies a central position in biological anthropology. The demonstrable relationship between temperature and morphology in extant primates (including humans) forms the basis of the interpretation of the Pleistocene hominin Homo neanderthalensis as a cold-adapted species. There are contradictory signals, however, in the pattern of primate craniofacial changes associated with climatic conditions. To determine the direction and extent of craniofacial change associated with temperature, and to understand the proximate mechanisms underlying cold adaptations in vertebrates in general, dry crania from previous experiments on cold- and warm-reared rats were investigated using computed tomography scanning and three-dimensional digitization of cranial landmarks. Aspects of internal and external cranial morphology were compared using standard statistical and geometric morphometric techniques. The results suggest that the developmental response to cold stress produces subtle but significant changes in facial shape, and a relative decrease in the volume of the maxillary sinuses (and nasal cavity), both of which are independent of the size of the skull or postcranium. These changes are consistent with comparative studies of temperate climate primates, but contradict previous interpretations of cranial morphology of Pleistocene Hominini.


Functional New Transcription Factors (TFs) Associated with Cervical Cancer.
The goal of this research was to find noval transcription factors (TFs) that are involved in cervical carcinogenesis. The Gene Expression Omnibus (GEO) database was utilized to analyze ten cervical cancer datasets using the Robust Rank Aggregation (RRA) technique. Survival and differential expression were validated using GEPIA (Gene Expression Profiling Interactive Analysis). The transcriptional regulatory network and putative targets were built using Cytoscape. A real-time PCR (quantitative real-time polymerase chain reaction) experiment was used to confirm the mRNA expression. Using public cervical cancer single-cell RNA-sequencing (scRNA-seq), bulk TCGA-CESC RNA-seq, and microarray datasets, coexpression correlations between putative targets and TFs were confirmed. After combining the results of 10 datasets, 8 TFs, including EMX2 (Empty Spiracles Homeobox 2), were chosen among 385 robust DEGs. In the normal female reproductive tract, EMX2 is extensively expressed, but it is reduced in cervical cancer. Overexpression EMX2 suppresses the proliferation of HeLa cells. 12 potential targets of EMX2 were selected. Our research has revealed evidence that EMX2 acted as a tumor suppressor in cervical cancer and PDZRN3 might be possible target of EMX2 in cervical cancer. It might be a therapeutic target in the future.


New York City group leads the way toward a more optimistic future for ASOs. ASO went from near bankruptcy to $26 million.
A do-it-yourself AIDS social organization: AIDS service organizations are struggling because of tighter reins on government funding, but an alternative organization in New York City is showing how it can be done. It has developed a successful social entrepreneur program that employs HIV-infected clients, pays them living wages, and makes money from retail, food services, and medical care business entities, contributing three-quarters of the organization's revenues.


[The development of newborn C 57 BL/KsJ-dbm mice produced from eggs fertilized in vitro].
The purpose of this study was to examine the development of newly born C57BL/KsJ-dbm mice produced from eggs fertilized in vitro. The embryos derived from fertilization in vitro (which was performed by using db/db eggs and adrenalectomized db/db (Adrex) spermatozoa,) were transferred to the oviduct of MRL/MpJ pseudopregnant recipients 30 hr after insemination. 376 of these embryos yielded 65 young. Weight gain and urine glucose, plasma glucose and insulin levels were measured in these young as well as in Adrex males. The young produced by fertilization in vitro showed hyperglycemia, hyperinsulinemia and obesity. The physiological abnormalities in these young were similar to those in db/db young produced by natural mating between heterozygote (db/+) males and females. Adrex males did not show hyperglycemia but did show hyperinsulinemia. These results indicate that in vitro fertilization and embryo transfer is an effective means of producing fetuses or newborns with an overt genotype in genetically diabetic obese (db) mice.


Oncoprecipitins from marine invertebrates are glycoproteins with a higher specificity to carcinoembryonic antigen.
Oncoprecipitins isolated from a number of marine invertebrates have been shown to be glycoproteins possessing a higher specificity to carcinoembryonic antigen (CEA)--similar to the interaction of antigen-antibody. The oncoprecipitin-CEA interaction was found to be substantially more specific than that of carbohydrate-containing polymers with lectins. Two oncoprecipitins, crustacin and cyprein, isolated from Pagurus prideauxii and Cyprea caputserpentis, respectively, have been characterized. The binding reaction of CEA with crustacin and cyprein failed to be inhibited with glycoproteins having sugar chain patterns closely related to those of CEA. Inhibition of the oncoprecipitin-CEA interaction with sugars was shown to be nonspecific and was observed only at sufficiently high concentrations of sugars used as inhibitors. Immunoenzymic assay of CEA content in normal and tumor tissues using CEA crustacin and CEA antiserum against CEA test systems revealed highly consistent results for both systems.


Alteration of Gut Microbial Metabolites in the Systemic Circulation of Patients with Parkinson's Disease.
Emerging evidence suggests that gut dysbiosis contributes to Parkinson's disease (PD) by signaling through microbial metabolites. Hippuric acid (HA), indole derivatives, and secondary bile acids are among the most common gut metabolites. To examine the relationship of systemic concentrations of these microbial metabolites associated with changes of gut microbiota, PD status, and severity of PD. We enrolled 56 patients with PD and 43 age- and sex-matched healthy participants. Motor and cognitive severity were assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III motor score and the Mini-Mental State Examination (MMSE), respectively. Plasma concentrations of targeted gut metabolites were measured with liquid chromatography-tandem mass spectrometry. Gut microbiota was analyzed with shotgun metagenomic sequencing. Compared with controls, PD patients had significantly higher plasma levels of HA, indole-3-propionic acid (IPA), deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA). After adjustment for age and sex in a multivariate logistic regression analysis, plasma levels of HA (odds ratio [OR] 3.21, p < 0.001), IPA (OR 2.59, p = 0.031), and GDCA (OR 2.82, p = 0.036) were associated with positive PD status. Concentrations of these gut metabolites did not correlate with MDS-UPDRS part III score or MMSE after adjustment for confounders. Microbial metabolite levels were associated with the relative abundance of pro-inflammatory gut bacteria. Aberrant gut microbial metabolites of HA, indole derivatives and secondary bile acids associated with specific gut microbiota changes were observed in patients with PD.


Classification of impulse radar waveforms using neural networks.
In this paper, it is demonstrated that multilayer neural networks, trained with the backpropagation algorithm and radial basis functions, can classify impulse radar waveforms from three different asphalt-covered bridge decks, each with its own structure. It might be thought that the thickness of asphalt and the depth of concrete over the reinforcing bars would be nearly constant for any one bridge deck; however in practice this is not the case. There are often significant changes in the thickness of the asphalt and the cover over reinforcement. Furthermore, a certain amount of damage to the concrete caused by severe winter climate often produces a random variation in the reflected waveforms obtained from different locations. These factors lead to a significant number of combinations of waveforms that can be obtained from any given structural type of deck. The classification accuracies achieved ranged between 89.9% and 100%. The accuracies achieved after using principal components analysis to reduce the dimensionality of the input data ranged between 95.6% and 100%.


Resection of radiation-induced sarcoma of the clavicle.
We report here the resection of a radiation-induced sarcoma (RIS) of the left clavicle developed in a 59-year-old woman 13 years after radiation for breast cancer. Surgery consisted of extirpation of the tumor with a combined resection of the total layer of the chest wall, the left brachiocephalic vein, and the left subclavian vein, reconstructed with a pediculated musculocutaneous graft using the right latissimus dorsi muscle. RIS of the clavicle is rare, and the prognosis might be poor. However, a complete removal of the tumor is feasible and can be performed safely.


[Intestinal lymphangiectasis: late complication of transportation of the great vessels corrected by the Mustard technic. A clinical case].
The Great Arteries Transposition corrected by Mustard's repair is often complicated with inferior vena cava obstruction with consequent intestinal lymphangiectasia and protein-losing enteropathy. We report a case of a 9 years old boy who underwent Mustard's repair and presented diarrhoea, abdominal pain, hypoproteinemia and ascites. The fecal elimination of 51Cr-labeled albumin was remarkable increased and the intestinal biopsy showed a noteworthy lymphangiectasia due to an hemodynamic overload. Therefore subjects with Great Arteries Transposition corrected by Mustard's repair should be valued in the post-surgical follow-up by 51Cr-labeled albumin fecal elimination and by intestinal biopsy, already sensitive in asymptomatic phase.


Use of a multiplex molecular beacon platform for rapid detection of methicillin and vancomycin resistance in Staphylococcus aureus.
Drug resistance, particularly vancomycin and methicillin resistance, in Staphylococcus aureus continues to emerge as a significant public health threat in both the hospital and community settings. In addition to the limited treatment options, S. aureus strains acquire and express numerous virulence factors that continue to increase its ability to cause a wide spectrum of human disease. As a result, empirical treatment decisions are confounded and there is a heightened need for a diagnostic test (or assay) to rapidly identify antibiotic resistance and specific virulence determinants and indicate the appropriate treatment. To that end we developed a platform using multiplex molecular beacon probes with real-time PCR for the rapid detection of drug resistance-determining genes and virulence factors in S. aureus. In this study, we demonstrate the specificity and sensitivity of our platform for detection of the genes conferring methicillin (mecA) and vancomycin (vanA) resistance as well as a gene encoding the virulence factor Panton-Valentine leucocidin (lukF) in S. aureus isolates.


Parasitic mites as part-time bodyguards of a host wasp.
Some bees and wasps that host mites have peculiar pocket-like structures called acarinaria. These have long been considered as morphological adaptations to securely transfer beneficial mites into nests, and thus are thought to be the product of a mutualistic relationship. However, there has been little compelling evidence to support this hypothesis. We demonstrated that the parasitic mite Ensliniella parasitica, which uses acarinaria, increases the reproductive success of its host wasp Allodynerus delphinalis by protecting it from parasitoid wasps. Every time the parasitoid Melittobia acasta accessed a prepupal or pupal wasp host cell, adult mites attacked it, continuously clinging to it and possibly piercing the intersegmental membrane of the parasitoid with their chelicerae. Subsequent mortality of the parasitoid depended on the number of attacking mites: an average of six mites led to a 70% chance of mortality, and 10 mites led to a 100% chance of mortality. In this way, parent mites protect the food source (juvenile wasps) for themselves and ultimately for their offspring. We propose that wasps evolved acarinaria to maintain this protective guarding behaviour.


[Infections caused by multiresistant bacteria].
Bacterial resistance to antibiotics is enhanced by antimicrobial selection pressure by antibiotics and the crossed transmission. Multiresistant bacteria (MRB) are involved in 1/5 of nosocomial infections and the 3/4 of the MRB are meticillin resistant Staphylococcus aureus and extended-spectrum-beta-lactamase-producing Enterobacteriaceae. The epidemic diffusion of these strains is still poorly controlled in our hospitals. The fight against the diffusion of these bacteria requires not only to screen patients harbouring antibiotic-resistant bacteria and respect hygiene measures, but also actions aiming at reducing the weight of selection pressure by antibiotics.


Metal-Free Three-Component Regioselective Aminofluorination of Styrene Derivatives.
The first metal-free, three-component radical aminofluorination of styrene derivatives has been developed, which employs Selectfluor as a fluorine source and azole derivatives as a nitrogen source. This transformation proceeds with high regioselectivity, providing various 1,2-aminofluorination compounds under mild conditions. Mechanistic studies suggest that the aminofluorination process might involve radical fluorination followed by nucleophilic amination.


Rational designs of structurally similar TADF and HLCT emitters with benzo- or naphtho-carbazole units as electron donors.
Thermally activated delayed fluorescence (TADF) and hybridized local and charge transfer (HLCT) emitters are two types of highly efficient electroluminescent materials which could improve their internal quantum efficiency (IQE) by converting triplet excitons to singlet ones. However, the molecular designs of TADF and HLCT materials are usually carried out separately because of their distinct emission mechanisms. In this work, we report a rational design strategy for the realization of switching between HLCT and TADF emissions in structurally similar donor-acceptor (D-A) type molecules, which are constructed with the same electron donors (benzo- or naphtho-carbazole) and acceptors with tunable electron-withdrawing abilities (benzonitrile (BN) and benzene-1,2,3,4,5-pentacarbonitrile (BPN)). Such switching of two types of emissions could be attributable to the modulation of the intramolecular charge transfer (ICT) and twist between donor and acceptor units. In the theoretical framework of the state hybridization, the excited-state properties are analyzed to reveal the intrinsic structure-property relationships for the donor-based HLCT and TADF molecules. This work not only offers an in-depth understanding of the excited-state properties of HLCT/TADF molecules, but also provides theoretical guidelines for the designing and screening of highly efficient electroluminescent materials.


Home-based exercise therapy for treating non-specific chronic low back pain.
To evaluate pain, functional capacity, and quality of life of patients with non-specific chronic low back pain, after home-based exercise therapy with different kinds of supervision. Thirty individuals of both gender, between 18 and 65 years old, performed the proposed exercises three times a week, for eight weeks. Group A (N = 17) performed the exercises after a single supervised session. Group B (N = 13) was supervised once a week at the rehabilitation center. Both groups received a booklet with instructions, and questionnaires to evaluate pain, functional capacity and quality of life; during the initial evaluation, after four and eight weeks. There was an improvement in pain and functional capacity between the initial evaluation and week 4, and the initial evaluation and week 8 in both groups (p <0.05). In the quality of life evaluation, the criteria for pain, functional capacity, and physical aspects had significant improvement after 8 weeks (p <0.05). There was no difference when comparing groups A and B (p >0,05). Home-based exercise therapy, when performed in a period of eight weeks, using the booklet, was effective for improving level of pain, functional capacity, and quality of life in patients with non-specific chronic low back pain. The weekly supervision did not significantly influence the final outcome between the groups.


Structural consequences of anionic host-cationic guest interactions in a supramolecular assembly.
The molecular structure of the spontaneously assembled supramolecular cluster [M(4)L(6)](n-) has been explored with different metals (M = Ga(III), Fe(III), Ti(IV)) and different encapsulated guests (NEt(4)(+), BnNMe(3)(+), Cp(2)Co(+), Cp*(2)Co(+)) by X-ray crystallography. While the identity of the metal ions at the vertices of the M(4)L(6) structure is found to have little effect on the assembly structure, encapsulated guests significantly distort the size and shape of the interior cavity of the assembly. Cations on the exterior of the assembly are found to interact with the assembly through either pi-pi, cation-pi, or CH-pi interactions. In some cases, the exterior guests interact with only one assembly, but cations with the ability to form multiple pi-pi interactions are able to interact with adjacent assemblies in the crystal lattice. The solvent accessible cavity of the assembly is modeled using the rolling probe method and found to range from 253-434 A(3), depending on the encapsulated guest. On the basis of the volume of the guest and the volume of the cavity, the packing coefficient for each host-guest complex is found to range from 0.47-0.67.


Synthesis of polynuclear Ag(I) and Au(I) complexes from macrocyclic tetraimidazolium salts.
The synthesis of the macrocyclic tetraimidazolium salt (H4-1)(Br)4 and the anion exchange to (H4-1)(PF6)4 have been explored. Deprotonation of (H4-1)(PF6)4 with Ag2O yields the mono- and dinuclear silver(I) complexes [Ag(H2-1)](PF6)3 and [Ag2(1)](PF6)2. Transmetallation of the dicarbene and tetracarbene ligands to gold(I) yields the mono- and dinuclear gold(I) complexes [Au(H2-1)](PF6)3 and [Au2(1)](PF6)2. The monosilver complex [Ag(H2-1)](PF6)3, featuring two imidazolium moieties, has been deprotonated and used for the synthesis of the tetranuclear silver(I) octacarbene complex [{Ag(1)}2Ag2](PF6)4.


Association of Sauropus androgynus and bronchiolitis obliterans syndrome: a hospital-based case-control study.
In late April 1995, an outbreak of a poorly defined respiratory illness related to the ingestion of leaves of Sauropus androgynus was observed in southern Taiwan. To further evaluate the association between S. androgynus and bronchiolitis obliterans syndrome, a hospital-based case-control study was conducted with one case group and three different control groups at Veterans General Hospital-Kaohsiung between April and September 1995. A total of 54 cases (50 females, 4 males), 54 age- and sex-matched neighborhood controls, 54 matched routine physical check-up controls, and 54 matched self-referred patron controls (who had ingested S. androgynus yet without obstructive physiology) were interviewed for clinical symptoms, history of S. androgynus consumption, and potential confounding factors. All 54 cases (100%) ingested S. androgynus compared with only five (9%) neighborhood controls (matched odds ratio (OR) incalculable, p < 0.001) and two (4%) physical check-up controls (matched OR incalculable, p < 0.001). In the univariate analysis of 54 cases and 54 self-referred patron controls, factors associated with an increased risk of bronchiolitis obliterans syndrome were methods of food preparation (uncooked juice vs. stir fried or boiled dishes, matched OR 10.3 (95% confidence interval (CI) 1.3-84.4)); preparer of the S. androgynus-containing food (vendor only vs. patient only or patient plus vendor, matched OR 2.8 (95% CI 1.1-7.1)); total S. androgynus consumption quantity (> 4,500 vs. 413-2,063 g, matched OR 10.0 (95% CI 1.9-53.0)); duration of consumption (> 45 vs. 6-24 days, matched OR 2.1 (95% CI 1.2-3.8)); and midterm interruption (< 2 vs. 2-5 days per week, matched OR 2.6 (95% CI 1.1-6.1)). Additionally, multiple conditional logistic regression analysis of cases and self-referred patron controls revealed that a larger total amount of S. androgynus consumption, preparation of S. androgynus food without cooking, and ingesting S. androgynus food prepared by a vendor were the significant risk factors associated with bronchiolitis obliterans syndrome.


Doped diamond-like carbon coatings for surgical instruments reduce protein and prion-amyloid biofouling and improve subsequent cleaning.
Doped diamond-like carbon (DLC) coatings offer potential antifouling surfaces against microbial and protein attachment. In particular, stainless steel surgical instruments are subject to tissue protein and resilient prion protein attachment, making decontamination methods used in sterile service departments ineffective, potentially increasing the risk of iatrogenic Creutzfeldt-Jakob disease during surgical procedures. This study examined the adsorption of proteins and prion-associated amyloid to doped DLC surfaces and the efficacy of commercial cleaning chemistries applied to these spiked surfaces, compared to titanium nitride coating and stainless steel. Surfaces inoculated with ME7-infected brain homogenate were visualised using SYPRO Ruby/Thioflavin T staining and modified epi-fluorescence microscopy before and after cleaning. Reduced protein and prion amyloid contamination was observed on the modified surfaces and subsequent decontamination efficacy improved. This highlights the potential for a new generation of coatings for surgical instruments to reduce the risk of iatrogenic CJD infection.