Differences in acute metabolism of fructose between hemodialysis patients and healthy subjects.
The consumption of fructose has increased dramatically during the last few decades and parallels the epidemics of obesity, metabolic syndrome, diabetes and chronic kidney disease (CKD). Fructose occurs naturally e.g. in fruit and in honey (rich in this monosaccharide) and as sucrose (table sugar). The effects of fructose have been attributed to the transient increases in serum uric acid levels during its metabolism. Recent research, also in CKD patients, has linked fructose to dysmetabolism of lipids, glucose and oxidative radicals. However, a general consensus of the potentially harmful effects of fructose is lacking. We improved a sensitive inulin assay for fructose measurement in serum and plasma and tested its accuracy in an acute experiment following consumption of pure fructose in controls. In addition, fructose and uric acid were analyzed postprandially during 240 min in six maintenance hemodialysis (HD) patients and nine healthy subjects consuming 190 ml cream/75 g sucrose in a fasting state. Whereas the fructose levels reached a maximum level after 60 min in controls they had not even started to decrease at 240 min in HD-patients. Likewise, while uric acid levels remained stable in controls they increased by 10% in HD patients at 240 min following the meal. In conclusion, a glucose and fat rich meal is associated with delayed absorption and/or metabolism of fructose in HD patients as well as increased serum uric acid levels.


Permanent nonselective His bundle pacing in an adult with L-transposition of the great arteries and complete AV block.
We report the placement of a permanent transvenous nonselective His bundle pacing lead in conjunction with a transvenous pacemaker/implantable cardioverter-defibrillator in an adult with Levo-Transposition of the Great Arteries (L-TGA) and a stenotic coronary sinus (CS) ostium, which would not accommodate a transvenous left ventricular (LV) pacing lead. Nonselective His bundle pacing provided a nearly identical ventricular activation pattern in this previously unpaced patient. Many L-TGA patients will have an eventual need for permanent pacing and, given the challenges of CS cannulation, His bundle pacing may represent a preferred modality rather than pure morphologic LV pacing or surgical systemic ventricular lead placement to achieve optimal electrical synchrony.


PD-1/PD-L1 inhibitor treatment and its impact on clinical imaging in non-small cell lung cancer: a systematic review and meta-analysis of immune-related adverse events.
In the contemporary era of cancer treatment, lung cancer (LC) holds the unenviable position of being the primary contributor to cancer-induced mortality worldwide. Although immunotherapy has expanded the therapeutic landscape for metastatic non-small cell lung cancer (NSCLC), the advent of immune checkpoint inhibitors has been accompanied by a concomitant increase in immune-related adverse events (irAEs). Timely detection of irAEs is pivotal for efficacious management and enhanced patient outcomes. Diagnostic imaging, encompassing x-ray and CT scans, can facilitate the identification and supervision of irAEs, thereby ensuring the prompt recognition of associated patterns and alterations for expeditious treatment. The present inquiry undertook a systematic exploration of multiple databases, incorporating a diverse array of studies such as randomized controlled trials and observational analyses. Patient demographics, imaging outcomes, and risk of bias were extracted from the data. Meta-analysis was executed utilizing R Statistical Software, with the results of the risk of bias assessment summarized accordingly. The analysis unveiled a higher prevalence of irAEs in patients receiving first-line treatment for NSCLC compared to those receiving subsequent treatments, with a statistically significant distinction observed for both high- and low-grade irAEs (p < 0.001). Pneumonitis, thyroiditis, and colitis emerged as the most frequently reported irAEs, whereas hepatitis and pancolitis were less commonly documented. This investigation signifies a crucial advancement in elucidating the function of imaging in the treatment of NSCLC with PD-1/PD-L1 inhibitors and emphasizes the imperative for ongoing research in this domain.


Mitochondrial alternative oxidase is determinant for growth and sporulation in the early diverging fungus Blastocladiella emersonii.
Blastocladiella emersonii is an early diverging fungus of the phylum Blastocladiomycota. During the life cycle of the fungus, mitochondrial morphology changes significantly, from a fragmented form in sessile vegetative cells to a fused network in motile zoospores. In this study, we visualize these morphological changes using a mitochondrial fluorescent probe and show that the respiratory capacity in zoospores is much higher than in vegetative cells, suggesting that mitochondrial morphology could be related to the differences in oxygen consumption. While studying the respiratory chain of the fungus, we observed an antimycin A and cyanide-insensitive, salicylhydroxamic (SHAM)-sensitive respiratory activity, indicative of a mitochondrial alternative oxidase (AOX) activity. The presence of AOX was confirmed by the finding of a B. emersonii cDNA encoding a putative AOX, and by detection of AOX protein in immunoblots. Inhibition of AOX activity by SHAM was found to significantly alter the capacity of the fungus to grow and sporulate, indicating that AOX participates in life cycle control in B. emersonii.


Psychological distress and quality of life in leprosy patients with neuropathic pain.
Leprosy is widely known because of progressive damage to the peripheral nerves. In spite of multidrug therapy, some patients develop chronic neuropathic pain after bacteriological cure. Chronic pain is associated with psychological distress and is also an important predictor of poor quality of life. The aim of this study is to assess psychological distress in leprosy patients with chronic neuropathic pain, and its repercussions on their quality of life. The sample of this cross-sectional study comprised patients with chronic neuropathic pain after multidrug therapy. Neuropathic pain was confirmed by clinical examination and by the Douleur neuropathique en 4 questions questionnaire. Pain intensity was assessed using a visual analogic scale (VAS) ruler. The psychological health of the participants was measured using the 12-item General Health Questionnaire, and the WHOQOL-bref was used to assess quality of life. The mean pain intensity reported by participants on the VAS was 7.1 cm (SD = 2.9). No differences in pain intensity with respect to gender were observed. Psychological distress was present in 76.2% of participants, being higher in those with Grade 2 of disability. Patients with psychological distress had the lowest mean scores in all domains of the WHOQOL-bref. The lowest mean scores according to domain were physical (9.9; SD = 3.3), followed by environment (11.9; SD = 3.0), psychological (13.5; SD = 2.6) and social relations (14.0; SD = 3.7). In conclusion, our study identified the presence of psychological distress in most of the participants. Patients with chronic neuropathic pain who were also found to have high psychological distress levels had higher pain intensity and a poorer quality of life.


Community dialogues for child health: results from a qualitative process evaluation in three countries.
Across the developing world, countries are increasingly adopting the integrated community case management of childhood illnesses (iCCM) strategy in efforts to reduce child mortality. This intervention's effectiveness is dependent on community adoption and changes in care-seeking practices. We assessed the implementation process of a theory-driven community dialogue (CD) intervention specifically designed to strengthen the support and uptake of the newly introduced iCCM services and related behaviours in three African countries. A qualitative process evaluation methodology was chosen and used secondary project data and primary data collected in two districts of each of the three countries, in purposefully sampled communities. The final data set included 67 focus group discussions and 57 key informant interviews, totalling 642 respondents, including caregivers, CD facilitators community leaders, and trainers. Thematic analysis of the data followed the 'Framework Approach' utilising both a deduction and induction process. Results show that CDs contribute to triggering community uptake of and support for iCCM services through filling health information gaps and building cooperation within communities. We found it to be an effective approach for addressing social norms around child care practices. This approach was embraced by communities for its flexibility and value in planning individual and collective change. Regular CDs can contribute to the formation of new habits, particularly in relation to seeking timely care in case of child sickness. This study also confirms the value of process evaluation to unwrap the mechanisms of community mobilisation approaches in context and provides key insights for improving the CD approach.


Quality education for undergraduates in pharmacology: a Canadian experiment.
Quality education in pharmacology requires the active participation of the student. This article by P.K. Rangachari describes a novel honours programme in biology and pharmacology at McMaster University, Hamilton, Ontario. The pharmacology courses are taught in a problem-based, self-directed and small-group format where students are encouraged to be responsible for seeking and critically assessing knowledge, communicating it effectively and gauging their own progress. These skills are reinforced by placing students in work terms in industry, government and university laboratories. This new programme has received high ratings from students, Faculty and employers.


Massaging over the greater occipital nerve reduces the intensity of migraine attacks: evidence for inhibitory trigemino-cervical convergence mechanisms.
Activation of the trigemino-cervical system constitutes one of the first steps in the genesis of migraine. The objective of this study was to confirm the presence of trigemino-cervical convergence mechanisms and to establish whether such mechanisms may also be of inhibitory origin. We describe a case of a 39-years-old woman suffering from episodic migraine who showed a significant improvement in her frontal headache during migraine attacks if the greater occipital nerve territory was massaged after the appearance of static mechanical allodynia (cortical sensitization). We review trigemino-cervical convergence and diffuse nociceptive inhibitory control (DNIC) mechanisms and suggest that the convergence mechanisms are not only excitatory but also inhibitory.


Marginal adaptation and microleakage of thixotropic and injection-capsule composites, an in vitro study.
The marginal integrity of MOD adhesive restorations of a thixotropic test composite (ZKP-A-5) and of two injection-capsule composites (Concise -capsule composite and Compocap-S) was examined. Dy penetration tests measured microleakage and scanning electron microscope evaluated marginal adaptation. The test restorations showed no improved micromorphological marginal adaptation when compared to those of a standard paste-paste composite (Concise). Compocap-S demonstrated better prevention of microleakage than did the other test preparations. The marginal quality of these thixotropic and injection-capsule composite restorations was improved from 34% to 52% with utilization of a sealer application (ZKP-A-2), (Concise-Enamel Bond). The application of a sealer prior to insertion of thixotropic and injection-capsule composites is, therefore, definitely indicated when these materials are used. The resultant restorations obtained with these test materials plus sealer correspond qualitatively to those of standard composites Concise or Adaptic [6,7]. The newly developed, complete composite systems (Nimetic, GC's Epolite 100/Epobond) demonstrated in comparison to Concise and Adaptic [6,7] inferior results.


MicroRNA-136 Promotes Vascular Muscle Cell Proliferation Through the ERK1/2 Pathway by Targeting PPP2R2A in Atherosclerosis.
Aberrant proliferation of vascular smooth muscle cells [VSMCs] is implicated in the pathogenesis of vascular pathologies such as atherosclerosis and restenosis. Accumulating evidences have revealed that microRNAs are involved in cell proliferation in various pathological conditions. In the present study, we showed that miR-136 was up regulated in human coronary atherosclerotic plaques when compared with normal coronary artery tissues. Moreover, miR-136 levels were up regulated in proliferative vascular smooth muscle cells induced by platelet-derived growth factor [PDGF] or serum. In cultured VSMCs, over expression of miR-136 stimulated cell proliferation. PPP2R2A was proved to be the direct target gene of miR-136 and knockdown of PPP2R2A had a proliferative effect on VSMCs. miR-136-induced PPP2R2A down-regulation was accompanied by increased expression of ERK1/2 phosphorylation. Inhibition of ERK1/2 abolished the effect of miR-136 and knockdown of PPP2R2A on VSMCs proliferation. In summary, aberrant miR-136 up regulation in atherosclerosis contributes to abnormal VSMC proliferation through suppressing the ERK1/2 pathway by targeting PPP2R2A. Our study also suggested that specific modulation of miR-136 in human VSMCs may provide a potential approach for the treatment of atherosclerosis.


Organization and activity of the Replantation Service for amputated hands in Poland.
A permanent on-call service for hand amputations (Replantation Service) was established in 2010 of the initiative of the Council of Polish Society for Surgery of the Hand. It is run by three qualified hand centres in Trzebnica, Poznań and Szczecin. Organization of this system, rules of activity and spectrum of cases admitted to replantation units was presented. A scheme of referral of amputations was shown and the main problems that appeared during almost three-year activity of the Service were discussed. Medico-legal and ethical implications arising from these problems were shown and organization of replantation service in other European countries was outlined. Establishing of the Replantation Service constituted a significant progress in the organization of the management of upper limb amputations. Thanks to that, over the period of three years, more than 200 patients were saved from severe disability, receiving a chance to regain an amputated limb.


Hexanucleotide Repeat Expansions in c9FTD/ALS and SCA36 Confer Selective Patterns of Neurodegeneration In Vivo.
A G4C2 hexanucleotide repeat expansion in an intron of C9orf72 is the most common cause of frontal temporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). A remarkably similar intronic TG3C2 repeat expansion is associated with spinocerebellar ataxia 36 (SCA36). Both expansions are widely expressed, form RNA foci, and can undergo repeat-associated non-ATG (RAN) translation to form similar dipeptide repeat proteins (DPRs). Yet, these diseases result in the degeneration of distinct subsets of neurons. We show that the expression of these repeat expansions in mice is sufficient to recapitulate the unique features of each disease, including this selective neuronal vulnerability. Furthermore, only the G4C2 repeat induces the formation of aberrant stress granules and pTDP-43 inclusions. Overall, our results demonstrate that the pathomechanisms responsible for each disease are intrinsic to the individual repeat sequence, highlighting the importance of sequence-specific RNA-mediated toxicity in each disorder.


Sorafenib induced hepatic encephalopathy.
A 60 year old male, known case of Hepatitis C related cirrhosis was diagnosed with exophytic Hepatocellular carcinoma (size 2.1 x 2.2 cm), Barcelona Clinic Liver Cancer Stage A, on routine surveillance. He refused liver Transplant and underwent laparoscopic segmental resection. Thereafter patient was started on Tablet Sorafenib 400mg twice daily to prevent recurrence of Hepatocellular carcinoma. On 18st post-operative day, patient presented with Hepatic encephalopathy. Routine investigations and MRI Brain were normal; Venous ammonia was high. Sorafenib was discontinued, and neurological symptoms resolved within 24 hours. The ammonia level decreased from 112 to 30 μmol/L. Hepatic encephalopathy recurred 14 days after Sorafenib reintroduction at a dose of 400 mg / day. It resolved within 24 hours of withdrawal of Sorafenib. Sorafenib induced recurrent acute overt Hepatic encephalopathy with biochemical corroboration is reported here.


Nasotracheal intubation-extubation-intubation and asleep-awake-asleep anesthesia technique for deep brain stimulation.
The asleep-awake-asleep (AAA) technique and laryngeal mask airway (LMA) is a common general anesthesia technique for deep brain stimulation (DBS) surgery. However, the LMA is not always the ideal artificial airway. In this report, we presented our experiences with nasotracheal intubation-extubation-intubation (IEI) and AAA techniques in DBS surgery for Parkinson's disease (PD) patients to meet the needs of surgery and ensure patients' safety and comfort. Three PD patients scheduled for DBS surgery had to receive general anesthesia for various reasons. For the first asleep stage, general anesthesia and nasotracheal intubation was completed with routine methods. During the awake stage, we pulled the nasotracheal tube back right above the epiglottis under fiberoptic bronchoscope (FOB) guidance for microelectrode recording (MER), macrostimulation testing and verbal communication. Once monitoring is completed, we induced anesthesia with rapid sequence induction and utilized the FOB to advance the nasotracheal tube into the trachea again. To minimize airway irritations during the process, we sprayed the airway with lidocaine before any manipulation. The neurophysiologists completed neuromoinitroing successfully and all three patients were satisfied with the anesthesia provided at follow-up. Nasotracheal IEI and AAA anesthetic techniques should be considered as a viable option during DBS surgery.


Epidemiology of Antibiotic Use and Antimicrobial Resistance in Selected Communities in Thailand.
To generate epidemiological information regarding antibiotic use and antimicrobial resistance (AMR) in targeted communities for use by the Thailand AMR Containment and Prevention Program. A survey of antibiotics sold by 215 grocery stores and retail shops located in the target communities was done by the local people who were instructed to purchase specified antibiotics and to present to such stores and shops with symptoms of sore throat, backache, common cold, acute diarrhea, inflamed uterus, and dysuria. The purchased drugs were then identified and recorded. Contamination of extended-spectrum β-lactamase (ESBL)-producing E. coli was identified in 174 samples of foods and open water sources collected from the target communities. Carriage of ESBL-producing E. coli in gastrointestinal tracts of 534 adults living in the target communities was performed by stool sample culture. One thousand three hundred one patients with upper respiratory infection (URI) and 235 patients with acute diarrhea who attended the tambon health promoting hospitals located in the target communities were monitored for their clinical outcomes of treatments. The patients with URI and acute diarrhea with no indication of antibiotic received symptomatic treatments as appropriate and they were followed via telephone contact every few days until all symptoms related to URI and acute diarrhea disappeared. The data were analyzed by descriptive statistics. Antibiotics were sold to the local people who were presenting with common ailments at many grocery stores and retail shops in their respective communities. In almost all cases, antibiotics were inappropriately given. Overall prevalence of ESBL-producing E. coli contamination in foods and open water sources was 26.4%. ESBL-producing E. coli was isolated from fresh meat and open water sources in many samples. Overall prevalence of ESBL-producing E. coli carriage in gastrointestinal tracts of the adults cultured was 66.5%. All patients with URI and acute diarrhea who had no indication of antibiotics and did not receive antibiotics had either cure or favorable response within seven days of start of symptomatic treatment. Antibiotics are widely available and are inappropriately sold and given by grocery stores and retail shops located within local communities in Thailand. Antibiotic-resistant bacteria commonly and freely circulate within the community. Patients with URI and acute diarrhea with no indication for antibiotic therapy can be treated without antibiotics. Findings and observations from this study will be used as part of a social marketing campaign on prevention and containment of AMR to educate people living within communities in Thailand.


Assessment of antibacterial activity of self-etching dental adhesive systems: An in vitro study.
To evaluate and compare the antibacterial activity of polymerized, two-step, self-etching and one-step, self-etching adhesive systems by using the direct contact test after one, seven, and fourteen days. The direct contact test was used to evaluate the antibacterial activity of Clearfil Protect Bond, Adper SE Plus, Clearfil SE Bond, and Adper Easy One on Streptococcus mutans after aging the samples in phosphate-buffered saline for one, seven, and fourteen days. Statistical analysis included the one-way Anova and Tukey's multiple comparison tests. Among the tested materials, Clearfil Protect Bond exhibited an antibacterial effect for seven days when in contact with S. mutans. None of the adhesive systems exhibited any antibacterial effect after 14 days. The incorporation of antibacterial agents into dentine-bonding agents may become an essential factor in inhibiting residual bacteria in the cavity following a cavity disinfection procedure, and it could be recommended in situations where total disinfection of cavity is not accomplished due to lack of accessibility.


Clinical features and treatment of dermatosis papulosa nigra in migrants to Italy.
Dermatosis papulosa nigra (DPN) is a benign epithelial tumor that is common in dark-skinned people. Although the diagnosis is easily made on medical examination, DPN is characterized by a chronic and worsening course. Therefore, even if DPN is a benign disease, the lesions are unaesthetic and the therapeutic options are quite inefficient. A prospective study was carried out during a period of 24 months (January 2006 to December 2007) at the Department for Preventive Medicine for Migration, Tourism and Tropical Dermatology of San Gallicano Dermatological Institute in Rome. Among 58 patients, 41 (71%) were women and 17 (29%) were men. The mean age was 33.5 years (range, 8-45 years). One pediatric patient was observed. This study is the first in Italy that, in recent years, has observed an important growth of the migration. The classic female predominance, family predisposition, and photodistribution of the lesion were found. DPN is frequently associated with patient discomfort, therefore the education of patients to reduce self-treatment is important.


The provisioned primate: patterns of obesity across lemurs, monkeys, apes and humans.
Non-human primates are potentially informative but underutilized species for investigating obesity. I examined patterns of obesity across the Primate order, calculating the ratio of body mass in captivity to that in the wild. This index, relative body mass, for n = 40 non-human primates (mean ± s.d.: females: 1.28 ± 0.30, range 0.67-1.78, males: 1.24 ± 0.28, range 0.70-1.97) overlapped with a reference value for humans (women: 1.52, men: 1.44). Among non-human primates, relative body mass was unrelated to dietary niche, and was marginally greater among female cohorts of terrestrial species. Males and females had similar relative body masses, but species with greater sexual size dimorphism (male/female mass) in wild populations had comparatively larger female body mass in captivity. Provisioned populations in wild and free-ranging settings had similar relative body mass to those in research facilities and zoos. Compared to the wild, captive diets are unlikely to be low in protein or fat, or high in carbohydrate, suggesting these macronutrients are not driving overeating in captive populations. Several primate species, including chimpanzees, a sister-species to humans, had relative body masses similar to humans. Humans are not unique in the propensity to overweight and obesity. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.


Treatment Modalities and Outcomes in Patients With Advanced Invasive Thymoma or Thymic Carcinoma: A Retrospective Multicenter Study.
We investigated the relationships between treatment characteristics and long-term outcomes in patients with locally advanced thymoma or thymic carcinoma. We retrospectively reviewed 146 patients treated from 1980 to 2011 at 2 tertiary cancer care centers, 110 with Masaoka-Koga stages III to IVA invasive thymoma and 36 with stages I to IVA thymic carcinoma. Survival probabilities were estimated using the Kaplan-Meier method. Risk factors related to survival were identified by univariate and multivariate competing risk analysis, with overall survival (OS) as the competing risk. The Cox regression analysis was used to identify risk factors for OS. Median follow-up time for all patients was 64 months. At 5 and 10 years, rates of OS and freedom from recurrence (FFR) were 81% and 58% and 81% and 65%, respectively. Of the patients who underwent surgery, trimodality treatment produced better survival compared with less aggressive treatment among patients with stage III disease (P=0.03). Among patients who underwent trimodality treatment, patients with stage III disease had better OS (P=0.03) and FFR (P<0.001) than those with stage IVA disease. On Cox regression analysis, decreased OS was associated with thymic carcinoma (hazard ratio [HR], 7.36; 95% confidence interval [CI], 2.38-22.77; P=0.001), R2/unresectable disease (HR, 8.45; 95% CI, 1.44-49.42; P=0.02), and an Eastern Cooperative Oncology Group performance score of 1 (HR, 8.14; 95% CI, 1.55-42.75; P=0.01) or 2 to 3 (HR, 29.60; 95% CI, 4.0-218.98; P=0.001) versus 0. Aggressive treatment with chemotherapy, surgical resection, and postoperative radiation therapy can produce long-term survival for patients with invasive thymic malignancies.


[Diagnosis of the health of a diabetic population in the county of Priorato in Tarragona province].
A health diagnosis made over a two-year period in the basic health area of Falset is described (17 municipalities with populations between 39 and 2,603 inhabitants, making-up a total reference population of 7,283 habitants) in relation to the diabetic population of the Priorato county in Catalunya. This county is geographically heterogeneous, with semi-arid hilly landscape, with poor communications, a farming population and a notoriously hostile climate. The population pyramid, inclined towards progressive aging of the population, is evidence of a major migration from the country. By means of continuous education of health personnel, updating of information sources, improvement of registration systems, and final evaluation, the outlines of an action plan is worked out with a view to the organisation of diabetic care in this rural context. A total of 226 diabetics were counted: 15 type 1 (6.2%), and 211 type II (93.8%). The incidence of diagnosed diabetes in the basic health area is 3.1% (1.4% to 10.33%). The average age of the patients was 65.6 years with a preponderance of women (146 = 64.6%). In 92 patients (40.2%) the evolution time was less than 5 years. The insulinisation rate was calculated at 26.1%. The typical diabetic patient is a retired person or a housewife (87.8), with primary of elementary education (82.7%), supported by the family.


Quantifying the iceberg effect for injury: using comprehensive community health data.
Injury is the leading cause of preventable morbidity and mortality in Canada. The "ice berg" effect in injuries was proposed to address the injury statistics that are often poorly documented. The aim of this investigation was to quantify the severity and magnitude of iceberg effect in Ontario, Canada. Data from Vital Statistics (1999, mortality), Canadian Institute for Health Information (2001, hospitalizations), Census (2001, demographic information), National Ambulatory Care Reporting System (2001, emergency department visits), and the Canadian Community Health Survey (2000/01, other injuries) were used to construct the Ontario injury iceberg for ages 12 years and older. There were 79,577 fatalities in Ontario in 1999; 2,645 were attributable to injuries (crude rate: 2.3 per 10,000). Of the 913,540 hospitalizations (2001), 67,301 were caused by injuries. There were 3,520,253 emergency department (ED) visits (2001) and 959,278 were attributable to injuries. For injuries treated elsewhere, the most common treatment site was the physician's office (23.3%). The most common cause of injuries (CCHS) was falls (37.4%) and exertion/movement (20.5%). There were 1,928,000 injuries causing functional impairment (one injury to five individuals in the population). INTERPRETATION The high ratio of injury-related ED visits to deaths illustrated the high volume of injuries that present to the ED. The ratio of injuries resulting in functional impairment to the population demonstrates.that such injuries can be problematic, even if not resulting in hospitalization. Constructing the injury iceberg using valid data should assist researchers and decision-makers in priority setting.


Selenophosphate Synthetase.
Selenophosphate synthetase, the selD gene product from Escherichia coli, is one of the enzymes required for the synthesis and specific insertion of selenocysteine into proteins directed by the TGA codon. Selenophosphate synthetases have been isolated from or are thought to be present in most organisms; however, the best characterized selenophosphate synthetase is from E. coli, in which both in vivo and in vitro studies have been performed. Leinfelder and coworkers showed that an E. coli mutant lacking an intact selD gene fails to incorporate Se into both the selenocysteine-containing enzyme formate dehydrogenase (FDH) and tRNA species that normally contain 2-selenouridine residues at the wobble position. Thus, this study strongly implicated selenophosphate as playing a major role in E. coli selenium metabolic pathways. The selenophosphate synthetase reaction requires some form of reduced selenium such as hydrogen selenide (HSe-) and ATP as substrates to generate a stoichiometric amount of SePO3, AMP, and orthophosphate. Studies of selenophosphate inhibition have provided further insight into the mechanism of selenophosphate synthetase. An assay by which AMP formation is measured in the absence of selenide showed that selenophosphate synthetase catalyzes hydrolysis of ATP to AMP and two orthophosphates in an uncoupled reaction. The sequencing of selenophosphate synthetase genes from various organisms reveals several conserved regions in the gene product. Recent investigations into the mechanism of selenophosphate synthetase have revealed a property of selenophosphate synthetase not previously observed. In samples of purified selenophosphate synthetase, an unusual optical absorption spectrum is seen.


[Interactions of antitubercular drugs].
Antituberculous drugs are never used alone but are often given concomitantly with drugs prescribed for other diseases. We have therefore reviewed the potential interactions of antituberculous drugs between themselves and with other drugs. Rifampicin being a potent enzyme inducer will decrease the plasma levels of a wide range of drugs. This in turn will decrease the effectiveness of these drugs if they are unmetabolized and active, or increase drug toxicity if the metabolites are toxic. Within the first category are the oral contraceptives, steroids, oral antidiabetics, oral anticoagulants and digitalis. Within the second category is thought to be isoniazid on account of its hepatotoxicity. In contrast, isoniazid (INH) is an enzyme inhibitor. Drugs with hepatic metabolism will tend to accumulate, although this seems clinically relevant only with antiepileptic drugs, diazepam, triazolam and oral anticoagulants (with high INH doses). Many other cases of drug interaction have been described, but they seem to be rare and may not be clinically relevant. INH and rifampicin do not seem to modify each other's metabolism consistently, but it may be wise to check the serum INH levels during coadministration. As said above, rifampicin does increase the hepatotoxicity of INH. INH also inhibits monoamine oxidase and will interact with other MAOI, as well as with fish, cheese or wine with high histamine or tyramine contents. The only interaction found with ethambutol is with diazepam: it increases its clearance and free fraction. Obviously, streptomycin potentiates the ototoxicity of other amino-glycosides, such as capreomycin, kanamycin or viomycin, so that combining them is strictly contra-indicated.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of tsl mutations on Col E1 expression in a recA strain of Escherichia coli K-12.
Spontaneous colicin production by Col E1 in a recA- strain of Escherichia coli K-12 is restored nearly to wild-type levels by the presence of tsl- second site mutation.


Identification of micro-RNAs in cotton.
The plant genome has conserved small non-coding microRNAs (miRNAs) genes about 20-24 nucleotides long. They play a vital role in the gene regulation at various stages of plant life. Their conserved nature among the various organisms not only suggests their early evolution in eukaryotes but also makes them a good source of new miRNA discovery by homology search using bioinformatics tools. A systematic search approach was used for interspecies orthologues of miRNA precursors, from known sequences of Gossypium in GenBank. The study resulted in 22 miRNAs belonging to 13 families. We found 7 miRNA families (miR160, 164, 827, 829, 836, 845 and 865) for the first time in cotton. All 22 miRNA precursors form stable minimum free energy (mfe) stem loop structure as their orthologues form in Arabidopsis and the mature miRNAs reside in the stem portion of the stem loop structure. Fifteen miRNAs belong to the world's most commercial fiber producing upland cotton (Gossypium hirsutum), five are from Gossypium raimondii and one each is from Gossypium herbaceum and Gossypium arboreum. Their targets consist of transcription factors, cell division regulating proteins and virus response gene. The discovery of 22 miRNAs will be helpful in future for detection of precise function of each miRNA at a particular stage in life cycle of cotton.


Virtue theory and abortion.
The sort of ethical theory derived from Aristotle, variously described as virtue ethics, virtue-based ethics, or neo-Aristotelianism, is becoming better known, and is now quite widely recognized as at least a possible rival to deontological and utilitarian theories. With recognition has come criticism, of varying quality. In this article I shall discuss nine separate criticisms that I have frequently encountered, most of which seem to me to betray an inadequate grasp either of the structure of virtue theory or of what would be involved in thinking about a real moral issue in its terms. In the first half I aim particularly to secure an understanding that will reveal that many of these criticisms are simply misplaced, and to articulate what I take to be the major criticism of virtue theory. I reject this criticism, but do not claim that it is necessarily misplaced. In the second half I aim to deepen that understanding and highlight the issues raised by the criticisms by illustrating what the theory looks like when it is applied to a particular issue, in this case, abortion.


Time-dependence of coronal seal of temporary materials used in endodontics.
The aim of this in vitro study was to compare parametrically the coronal seal ability over different periods of times of four restorative materials used to seal the pulpal access cavity after endodontic treatment. One hundred and thirty-five mandibular premolars were divided randomly into three time groups (1, 2 and 4 weeks), each of which was in turn divided into four subgroups. Each subgroup was restored using one of four restorative materials: Coltosol, glass ionomer cement (GIC), zinc phosphate (ZP) cement, or intermediate restorative material (IRM) cement. The root canals were prepared using the crown-down technique, and obturated using lateral condensation. Following placement of the restorative material, the samples were incubated in distilled water at 37 degrees C and were subjected to 50 thermocycles (0 +/- 4, 56 +/- 4C). After immersing in (2%) methylene blue dye for 24 h, teeth were longitudinally sectioned and examined under a stereomicroscope. The results showed that Coltosol and GIC cement were significantly superior in sealing ability to ZP and IRM cements (P < 0.05). There was no significant difference between GIC cement and Coltosol. Both Coltosol and GIC after 1 week were significantly better than 4 weeks. There was no significant difference in the seal ability at different time periods when ZP and IRM cements were used.


Down-regulation of dopamine transporter and abnormal behavior in STAT6-deficient mice.
To determine the role of STAT6 transcription factors in brain function, we performed a battery of mouse behavioral analyses of STAT6-deficient mice and made comparisons with wild-type mice. STAT6-deficient mice were significantly more hyperactive in the final two blocks of an open field test, indicating abnormal habituation in completing the task. Two learning tasks, a water maze and a passive avoidance test, were mastered by STAT6-deficient mice as effectively as the wild-type. RT-PCR analysis suggested that the levels of dopamine transporter (DAT) mRNA may be lower in the midbrain of the mutant. In agreement with the finding, subsequent Western blotting and immunohistochemical analysis demonstrated lower levels of DAT protein in the mutant striatum. These results lead to the proposal that, in addition to being a pivotal transcription factor in the immune system, STAT6 may be crucially implicated in mouse behavior by modulating the expression of neuronal genes such as DAT.


Generation of Null Mutants to Elucidate the Role of Bacterial Glycosyltransferases in Bacterial Motility.
The study of glycosylation in prokaryotes is a rapidly growing area. Bacteria harbor different glycosylated structures on their surface whose glycans constitute a strain-specific barcode. The associated glycans show higher diversity in sugar composition and structure than those of eukaryotes and are important in bacterial-host recognition processes and interaction with the environment. In pathogenic bacteria, glycoproteins have been involved in different stages of the infectious process, and glycan modifications can interfere with specific functions of glycoproteins. However, despite the advances made in the understanding of glycan composition, structure, and biosynthesis pathways, understanding of the role of glycoproteins in pathogenicity or interaction with the environment remains very limited. Furthermore, in some bacteria, the enzymes required for protein glycosylation are shared with other polysaccharide biosynthetic pathways, such as lipopolysaccharide and capsule biosynthetic pathways. The functional importance of glycosylation has been elucidated in several bacteria through mutation of specific genes thought to be involved in the glycosylation process and the study of its impact on the expression of the target glycoprotein and the modifying glycan. Mesophilic Aeromonas have a single and O-glycosylated polar flagellum. Flagellar glycans show diversity in carbohydrate composition and chain length between Aeromonas strains. However, all strains analyzed to date show a pseudaminic acid derivative as the linking sugar that modifies serine or threonine residues. The pseudaminic acid derivative is required for polar flagella assembly, and its loss has an impact on adhesion, biofilm formation, and colonization. The protocol detailed in this article describes how the construction of null mutants can be used to understand the involvement of genes or genome regions containing putative glycosyltransferases in the biosynthesis of a flagellar glycan. This includes the potential to understand the function of the glycosyltransferases involved and the role of the glycan. This will be achieved by comparing the glycan deficient mutant to the wild-type strain.


Effect of psychological skill training as a psychological intervention for a successful rehabilitation of a professional soccer player: single case study.
The purpose of this study is developing and applying psychological skill training (PST) program as one of the methods of intervention for psychological rehabilitation in order for a successful recovery of the professional soccer player (K). He is currently on rehabilitation training after an injury, and we tried to see the results of this program. It was designed as a program of 17 sessions including 3 interviews and diagnostic checks (psychological skill questionnaire: PSQ, profiles of mood states: POMS) and 14 sessions of PST (goal setting, anxiety reduction, concentration, confidence). After the application of the program, the levels of anxiety reduction, goal setting, concentration, and confidence were visibly increased, and in POMS, which is an indicator of physical rehabilitation process of K, vigor was increased. Meanwhile negative emotions, such as tension, depression, and fatigue were decreased. This program was developed for K, and therefore it has some difficulties in applying it to other players. However, the significance of this study is that it could serve as a basis on developing programs for other players in the rehabilitation process. In addition, it has also proven that PST can be used as a successful method for psychological rehabilitation intervention.


[Role of mitochondria in the process of steroidogenesis induced by gonadotropins].
Specific inhibitors of RNA and protein synthesis in mitochondria, ethidium bromide and chloramphenicol, suppress the increase in the uterine weight of sexually immature mice and the in vitro maturation of oocytes of anuran amphibians induced by gonadotropins. The effect of steroid hormones on the uterus of mice and the oocytes of amphibians is not prevented by the inhibitors of macromolecular syntheses in mitochondria. In in vivo experiments, the doses of ethidium bromide inhibiting RNA synthesis in the liver mitochondria of mice stimulate RNA synthesis in the nuclei. This stimulation is accompanied by the increase in the activity of RNA polymerases. The possible involvement of mitochondrial genome in the gonadotropin-induced steroidogenesis is discussed.


Comparison of Holsteins selected for high and average milk production. 1. Net income and production response to selection for milk.
The objective of the experiment was to quantify differences between two divergent lines of Holsteins for net income per day, per lactation, and per life-time using a linear profit function. Data consisted of 2768 lactation records from 1078 Holstein cows by 140 sires. Bulls with high PD milk were mated to daughters of sires with high PD for milk, and bulls with average PD for milk were mated to cows of average genetic merit, creating two divergent genetic lines of cattle. Data on production, health, and reproduction were collected. Analyses were based on lactation and lifetime. High line cows had greater net returns than average line cows by $.30/d (16.0%) per lactation and $.33 (19%) advantage/d of life. The high line cows were $103.79 more profitable (20.4%) per lactation and $375.60 (17.4%) more profitable during their lifetime than their average line herdmates. This income superiority was because high line cows averaged 940 kg more milk per lactation (16.4%) and 3435 kg more milk per lifetime (15.7%) than the average line cows. High line cows were superior by 500 kg for PTA for milk from January 1990. Selecting sires with high PD for milk effectively improved milk production and increased net income.


Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer.
Trastuzumab is an effective treatment for patients with metastatic breast cancer (MBC) that overexpresses HER-2. A high incidence of brain metastases (BM) has been noted in patients receiving trastuzumab. A retrospective chart review was conducted of 100 patients commencing trastuzumab for metastatic breast cancer from July 1999 to December 2002, at the Christie Hospital. Seven patients were excluded; five patients developed central nervous system metastases prior to starting trastuzumab, and inadequate data were available for two. Out of the remaining 93 patients, 23 (25%) have developed BM to date. In all, 46 patients have died, and of these 18 (39%) have been diagnosed with BM prior to death. Of the 23 patients developing BM, 18 (78%) were hormone receptor negative and 18 (78%) had visceral disease. Univariate analysis showed a significant association between the development of cerebral disease and both hormone receptor status and the presence of visceral disease. In conclusion, a high proportion of patients with MBC treated with trastuzumab develop symptomatic cerebral metastases. HER-2-positive breast cancer may have a predilection for the brain, or trastuzumab therapy may change the disease pattern by prolonging survival. New strategies to address this problem require investigation in this group of patients.


The anti-leukemic Bruton's tyrosine kinase inhibitor alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl) propenamide (LFM-A13) prevents fatal thromboembolism.
The leflunomide metabolite analog alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13) is a rationally-designed specific inhibitor of the TEC family protein tyrosine kinase, Bruton's tyrosine kinase (BTK) which plays an important role in platelet physiology by regulating the glycoprotein GPVI-FcRgamma-coupled collagen receptor signaling pathway. At low micromolar concentrations, LFM-A13 inhibited collagen-induced ultrastructural changes indicative of activation. LFM-A13 inhibited collagen (but not thrombin, TRAP-6, or ADP)-induced platelet aggregation in a concentration-dependent fashion with an IC50 value of 2.8 microM. LFM-A13 was not toxic to mice when administered systemically at dose levels ranging from 1 to 100 mg/kg. At nontoxic dose levels, LFM-A13 prolonged the tail bleeding times of mice and improved event-free survival in two mouse models of agonist-induced invariably fatal pulmonary thromboembolism. To our knowledge, LFM-A13 is the first anti-thrombotic agent which prevents platelet aggregation by inhibiting BTK.


Congenital Internal Jugular Phlebectasia: An Anomaly Still Poorly Recognized.
Congenital internal jugular phlebectasia (CIJP) is a rare condition characterized by congenital dilatation of the vein without tortuosity that becomes more evident during straining as a lateral neck mass. CIJP often remains undiagnosed from a few months to several years after the onset of the swelling. It is frequently asymptomatic although symptomatic cases have been occasionally reported. We present the case of a healthy 7-year-old boy with a lateral neck mass, triggered by the Valsalva maneuver. Neck ultrasound (US) showed right internal jugular axial ectasia, increasing during the Valsalva maneuver; contrast computed tomography (CT) scan confirmed a fusiform dilatation of the right internal jugular vein. Due to the lack of symptoms, we treated our patient conservatively. At 5 years of follow-up, the patient is still asymptomatic, with no evidence of complications or thrombosis. Due to its self-limiting nature, treatment for asymptomatic cases of CIJP should be conservative, providing a follow-up with both clinical and US annual evaluations.


Biomolecule-directed assembly of binary gold and titanium dioxide nanoparticles.
We report in this paper a novel strategy for "bottom-up" assembly of two types of metallic and semiconductor nanoparticles. By only using a small biomolecule, coenzyme A, as a "linker" to direct the assembly of metallic gold and semiconductor titanium dioxide nanoparticles, the usual biomolecule-directed system can be greatly simplified. Effects of experimental conditions on the formation of binary nanoparticles are studied. This strategy using single small biomolecule to direct assembly of nanoparticles is proven to be efficient, facile and non-toxic and should be extendable to other building blocks.


Clinical significance of epithelial-mesenchymal transition and cancer stem cells.
Purpose: Spread of cancer cells from the organ of the origin of them to another location, namely metastasis, is one of the most important factors that complicate the treatment of cancer. Therefore, research for the treatment of metastatic disease is gaining importance, especially for advanced cancers. This research focuses on the mechanisms that facilitate the metastatic tendency of cancer cells. Therefore, epithelial-mesenchymal transition (EMT) mechanism that helps the cells become metastatic and cancer stem cells (CSCs) present in the heterogeneous tumor mass are in the center of these researches.


Preoperative body mass index-to-prognostic nutritional index ratio predicts pancreatic fistula after pancreaticoduodenectomy.
Estimating or scoring the risk of post-operative pancreatic fistula (POPF) may help with selection of high-risk patients and individualized patient consent. However, there are no simple and reliable preoperative predictors of POPF used in daily clinical practice. We investigated the utility of body mass index-to-prognostic nutritional index (BMI/PNI) ratio as a preoperative marker to predict the development of POPF in 87 patients undergoing pancreaticoduodenectomy. The overall incidence of clinical (grade B/C) POPF was 17% (15 of 87 patients). Among various pre-, intra-, and post-operative variables analyzed, higher BMI and lower PNI were identified as independent predictors for POPF by multivariate analysis. We therefore investigated BMI/PNI ratio as a preoperative predictor for POPF. BMI/PNI ratio was significantly higher in patients with POPF than in those without POPF (0.54 vs. 0.45, P=0.0007). A receiver operating characteristic (ROC) curve analysis demonstrated a fair capability of BMI/PNI ratio to predict the occurrence of POPF (area under the ROC curve 0.781). With a cut-off value of 0.5, the sensitivity, specificity, and diagnostic accuracy of BMI/PNI ratio to predict POPF was 73%, 74%, and 74%, respectively. In particular, when restricted to a subgroup of elderly (≥75 years old) male patients, the sensitivity, specificity, and diagnostic accuracy of BMI/PNI ratio was 100%, 100%, and 100%, respectively. The BMI/PNI ratio is a simple preoperative marker to predict the occurrence of POPF after pancreaticoduodenectomy.


Anti-HSV-1 and HSV-2 Flavonoids and a New Kaempferol Triglycoside from the Medicinal Plant Kalanchoe daigremontiana.
Kalanchoe daigremontiana (Crassulaceae) is a medicinal plant native to Madagascar. The aim of this study was to investigate the flavonoid content of an aqueous leaf extract from K. daigremontiana (Kd), and assess its antiherpetic potential. The major flavonoid, kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside (1), was isolated from the AcOEt fraction (Kd-AC). The BuOH-soluble fraction afforded quercetin 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside (2) and the new kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-α-l-rhamnopyranoside-7-O-β-d-glucopyranoside (3), named daigremontrioside. The crude extract, Kd-AC fraction, flavonoids 1 and 2 were evaluated using acyclovir-sensitive strains of HSV-1 and HSV-2. Kd-AC was highly active against HSV-1 (EC50 = 0.97 μg/ml, SI > 206.1) and HSV-2 (EC50 = 0.72 μg/ml, SI > 277.7). Flavonoids 1 and 2 showed anti-HSV-1 (EC50 = 7.4 μg/ml; SI > 27 and EC50 = 5.8 μg/ml; SI > 8.6, respectively) and anti-HSV-2 (EC50 = 9.0 μg/ml; SI > 22.2 and EC50 = 36.2 μg/ml; SI > 5.5, respectively) activities, suggesting the contribution of additional substances to the antiviral activity.


The imaging photopolarimeter experiment on pioneer 10.
A 2.5-centimeter telescope aboard Pioneer 10 is capable of making two-dimensional spin-scan maps of intensity and polarization in red and blue light at high spatial resolution. During the recent flyby of Jupiter, a large quantity of imaging and polarimetric data was obtained on Jupiter and the Galilean satellites over a wide range of phase angles.


A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis.
Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin used in the treatment of tuberculosis may be suboptimal in some patients, leading to worse tuberculosis treatment outcomes and emergence of drug resistance. Furthermore, a drug interaction with the rifamycins results in up to 31% reduced plasma concentrations of moxifloxacin when these are combined for treatment of drug-susceptible tuberculosis, although the clinical relevance of this interaction is unclear. Moxifloxacin exhibits extensive interindividual pharmacokinetic variability. Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens.


Reduced systemic bone mineral density associated with a rare case of tooth and nail syndrome.
This is the first report of a rare genetic tooth and nail syndrome (TNS) diagnosed in a 14-year-old Caucasian girl with a complete absence of the permanent dentition and, additionally, reduced total and lumbar spine bone mineral density (BMD). This coincidence suggests a new clinical manifestation of the disorder in which genetic factors and/or shared mechanisms may be responsible for the deterioration of the stomatognathic system, anodontia, nail phenotype and osteopenia. Low bone mass appears to be a new component of the syndrome. There is a rationale for bone densitometry scans assuming that patients with TNS may have an increased risk of osteopenia. Reduced BMD and, possibly, impaired bone quality and strength may produce difficulties or even exclude such patients from future treatment with dental implants.


Evaluation of the influence of the aqueous phase bioconstituent environment on the F-19 T1 of perfluorocarbon blood substitute emulsions.
Oxygen-sensitive F-19 magnetic resonance imaging of perfluorocarbon compounds requires that fluorocarbon T1 changes correlate with the local PO2 and not with the composition of the surrounding aqueous phase. The influence of various bioconstituents and paramagnetic ions within the aqueous phase on the F-19 fluorocarbon phase T1 for PFC emulsions was evaluated at 0.14 and 0.66 T. T1 was measured for FC-43, perflubron, and a fluorinated surfactant. Controlled variables introduced in the aqueous phase included annex solution constituents, blood, pH changes, and Gd-DTPA. For a constant PO2, the F-19 T1s were independent of the emulsion constituents, blood concentration, and pH. For FC-43 and perflubron, F-19 T1 was independent of the Gd-DTPA concentration, while the aqueous phase T1 decreased by more than an order of magnitude. XMO-10 (smallest emulsion particle size) showed a slight decrease in F-19 T1 with increasing Gd-DTPA concentration at 0.66 T.


Evaluation of a low-technology system to obtain morphological and mobility trial measurements in dogs and investigation of potential predictors of canine mobility.
To develop a low-technology system that can be used by dog owners to obtain morphological and mobility measurements in companion dogs as candidate components of an eventual canine frailty scale. 57 adult (≥ 1-year-old) dogs enrolled by 43 owners. Morphological measurements of dogs were performed by investigators and dog owners. Dogs participated in timed in-clinic mobility trials across a flat surface (on-leash trial with the owner, on-leash trial with the investigator, and off-leash trial) and on stairs; each trial was repeated 3 times. Owners were asked to conduct a second stair trial at home 2 weeks later. Agreement between owner- and investigator-obtained measurements was assessed with Shrout-Fleiss intraclass correlation coefficients and paired t tests. Age, quartile of projected percentage of mean life span attained (adjusted for body weight), and height were evaluated as predictors of speed and stride length in mobility trials with linear regression and Spearman rank correlation analysis. Agreement between owner- and investigator-obtained morphological measurements was strong. Age was a weak but significant predictor of decreased dog speed in mobility trials (adjusted R2, 0.10 to 0.23). Speed decreased significantly with increasing quartile of projected life span attained. A linear regression model that included height and age predicted dog speed better than models with age or height alone. Morphological and mobility trial measurements can be obtained by dog owners with minimal training. Low-technology measurements of mobility trial speed offer potential as components in a future scoring scale for canine frailty.


Alterations of the surface tegument of Opisthorchis viverrini exposed to praziquantel in vitro and in vivo.
The in vitro and in vivo effects of praziquantel on the ultrastructural surface of Opisthorchis viverrini were investigated using scanning electronmicroscopy. For the in vitro study, adult flukes were collected from experimentally infected hamsters, and were incubated for various time intervals at 37 degrees C in Earle's basal medium containing praziquantel at final concentrations of 0.01-100 micrograms/ml. For the in vivo study, flukes were collected from the biliary system of experimentally infected hamsters that had been treated 4 hours previously with 350 mg of praziquantel per kg body weight (mg/kg). Flukes were also obtained from the feces of a patient with opisthorchiasis who had been given praziquantel once at a dose of 40 mg/kg 4-6 hours previously and from the bile of a patient at the time of operation 24 hours after praziquantel treatment. Scanning electronmicroscopic analyses of the surface teguments of flukes exposed to praziquantel either in vitro or in vivo showed similar changes. Tegumental bubbles of different sizes appeared on the surface; they later ruptured and resulted in the formation of crater-like lesions. These lesions might be so extensive as to result in the peeling of the entire areas. On occasions, "micronodules" appeared later in these areas and those at the periphery of the lesions; these micronodules may represent an attempt by the worm to regenerate new tegument. The possibility that these ultrastructural changes may represent a generalized response of the tegumental surface to an obnoxious agent was discussed.


Extensive variation in chromosome number and genome size in sexual and parthenogenetic species of the jumping-bristletail genus Machilis (Archaeognatha).
Parthenogenesis in animals is often associated with polyploidy and restriction to extreme habitats or recently deglaciated areas. It has been hypothesized that benefits conferred by asexual reproduction and polyploidy are essential for colonizing these habitats. However, while evolutionary routes to parthenogenesis are manifold, study systems including polyploids are scarce in arthropods. The jumping-bristletail genus Machilis (Insecta: Archaeognatha) includes both sexual and parthenogenetic species, and recently, the occurrence of polyploidy has been postulated. Here, we applied flow cytometry, karyotyping, and mitochondrial DNA sequencing to three sexual and five putatively parthenogenetic Eastern-Alpine Machilis species to investigate whether (1) parthenogenesis originated once or multiply and (2) whether parthenogenesis is strictly associated with polyploidy. The mitochondrial phylogeny revealed that parthenogenesis evolved at least five times independently among Eastern-Alpine representatives of this genus. One parthenogenetic species was exclusively triploid, while a second consisted of both diploid and triploid populations. The three other parthenogenetic species and all sexual species were diploid. Our results thus indicate that polyploidy can co-occur with parthenogenesis, but that it was not mandatory for the emergence of parthenogenesis in Machilis. Overall, we found a weak negative correlation of monoploid genome size (Cx) and chromosome base number (x), and this connection is stronger among parthenogenetic species alone. Likewise, monoploid genome size decreased with elevation, and we therefore hypothesize that genome downsizing could have been crucial for the persistence of alpine Machilis species. Finally, we discuss the evolutionary consequences of intraspecific chromosomal rearrangements and the presence of B chromosomes. In doing so, we highlight the potential of Alpine Machilis species for research on chromosomal and genome-size alterations during speciation.


Lambda-Interferons Inhibit Herpes Simplex Virus Type 2 Replication in Human Cervical Epithelial Cells by Activating the JAK/STAT Pathway.
Herpes simplex virus type 2 (HSV-2) is associated with a variety of diseases that are health problems worldwide. Our early study showed that lambda-interferons (IFN-λs), induced by the activation of the Toll-like receptor 3 and retinoic acid-inducible protein I signaling pathways, contribute to inhibition of HSV-2 replication in human cervical epithelial cells. However, anti-HSV-2 mechanisms and specific differences in signaling transduction by different IFN-λs in human cervical epithelial cells remain unclear. In this study, we demonstrated potent inhibition of HSV-2 replication by IFN-λs without cytotoxicity. Investigation of the underlying mechanism(s) showed that IFN-λs induced expression of IFN-stimulated genes (ISGs) and enhanced the expression of several pattern recognition receptors (PRRs). Among the IFN-λs, IFN-λ3 induced higher levels of ISG and PRR expression. In addition, IFN-λs up-regulated a number of genes that encode components of the Janus kinase signal transducers and activators of transcription (JAK/STAT) signaling pathway. Inhibition of the JAK/STAT signaling pathway by a JAK inhibitor abolished IFN-λ-mediated anti-HSV-2 activity and induction of ISGs and PRRs, whereas the induction of ISGs and PRRs by IFN-λs was not compromised by HSV-2 infection. These findings provide further experimental evidence that IFN-λs have therapeutic potential for HSV-2 infections.


hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway.
Circular RNA has been reported to play a key role in neuroblastoma (NB); however, the role of circ_0000285 in NB remains unclear. The aim of this study was to elucidate the role of circ_0000285 in NB. We studied the expression patterns of miR-582-3p and circ_0000285 in NB tissues and cells using real-time quantitative polymerase chain reaction. The expression of proteins associated with apoptosis (Bax and Bcl-2) and the proteins associated with Wnt/β-catenin (Wnt, p-Gsk-3β, Gsk-3β, β-catenin, and C-myc) were quantified by western blotting. In vivo animal models were prepared for the functional verification of circ_0000285 on tumor growth. The potential binding of circ_0000285 to miR-582-3p was ascertained using dual-luciferase reporter and RNA-binding protein immunoprecipitation experiments. Noticeable upregulation of circ_0000285 expression was observed in NB tumor samples and cell lines. In vivo and in vitro experiments indicated that the absence of circ_0000285 repressed NB cell proliferation and migration, provoked apoptosis, and impaired the activity of Wnt/β-catenin signaling. miR-582-3p is targeted by circ_0000285 and is poorly expressed in NB cells. The additional repression of miR-582-3p in NB cells after circ_0000285 silencing largely recovered circ_0000285 silencing-suppressed NB cell proliferation and migration and enhanced apoptosis. The absence of miR-582-3p restored Wnt/β-catenin signaling activity impaired by the knockdown of circ_0000285. circ_0000285 functions as an miR-582-3p sponge to strengthen Wnt/β-catenin signaling activity, thus exacerbating NB development.


ZnO Nanorod Logic Circuits.
Logic devices, including OR, AND, NOT, and NOR gates, based on single-crystalline ZnO nanorods are demonstrated. In these devices, ZnO nanorods are employed as semiconducting channels. They control metal/oxide semiconductor junction characteristics, to yield either good ohmic or Schottky contacts, ensuring fabrication of high-performance Schottky diodes and metal-semiconductor field-effect transistors.


Comparative properties of Amazonian oils obtained by different extraction methods.
Pequi (Caryocar brasiliense Camb.), babaçu (Orbignya phalerata Mart.), buriti (Mauritia flexuosa), and passion fruit (Passiflora edulis) oils were studied to determine their antibacterial, antioxidant and cytotoxic activities, as well as their total phenol and carotenoid contents. The fatty acid contents were determined by GC-MS. The three types of passion fruit oils studied were refined, cold pressed or extracted from seeds in a Soxhlet apparatus. The oils thus obtained showed differences in antioxidant activity and carotenoid content, but were similar in regard to total phenols. Buriti and pequi had the highest carotenoid contents, while refined and cold pressed passion fruit oil displayed the highest antioxidant activity. Pequi oil was the only oil to display antibacterial and cytotoxic activity.


A Review of the Pathophysiological Mechanisms Underlying Castration-resistant Prostate Cancer.
Androgen deprivation therapy or ADT is one of the cornerstones of management of locally advanced or metastatic prostate cancer, alongside radiation therapy. However, despite early response, most advanced prostate cancers progress into an androgen unresponsive or castrate resistant state, which hitherto remains an incurable entity and the second leading cause of cancer-related mortality in men in the US. Recent advances have uncovered multiple complex and intermingled mechanisms underlying this transformation. While most of these mechanisms revolve around androgen receptor (AR) signaling, novel pathways which act independently of the androgen axis are also being discovered. The aim of this article is to review the pathophysiological mechanisms that help bypass the apoptotic effects of ADT to create castrate resistance. The article discusses castrate resistance mechanisms under two categories: 1. Direct AR dependent pathways such as amplification or gain of function mutations in AR, development of functional splice variants, posttranslational regulation, and pro-oncogenic modulation in the expression of coactivators vs corepressors of AR. 2. Ancillary pathways involving RAS/MAP kinase, TGF-beta/SMAD pathway, FGF signaling, JAK/STAT pathway, Wnt-Beta catenin and hedgehog signaling as well as the role of cell adhesion molecules and G-protein coupled receptors. miRNAs are also briefly discussed. Understanding the mechanisms involved in the development and progression of castration-resistant prostate cancer is paramount to the development of targeted agents to overcome these mechanisms. A number of targeted agents are currently in development. As we strive for more personalized treatment across oncology care, treatment regimens will need to be tailored based on the type of CRPC and the underlying mechanism of castration resistance.


Membrane-induced secondary structures of neuropeptides: a comparison of the solution conformations adopted by agonists and antagonists of the mammalian tachykinin NK1 receptor.
We present what we believe to be the first documented example of an inducement of distinctly different secondary structure types onto agonists and antagonists selective for the same G-coupled protein receptor using the same membrane-model matrix wherein the induced structures are consistent with those suggested to be biologically active by extensive analogue studies and conventional binding assays. 1H NMR chemical shift assignments for the mammalian NK1 receptor-selective agonists alpha-neurokinin (NKA) and beta-neurokinin (NKB) as well as the mammalian NK1 receptor-selective antagonists [d-Pro2,d-Phe7,d-Trp9]SP and [d-Arg1, d-Pro2,d-Phe7,d-His9]SP have been determined at 600 MHz in sodium dodecyl sulfate (SDS) micelles. The SDS micelle system simulates the membrane-interface environment the peptide experiences when in the proximity of the membrane-embedded receptor, allowing for conformational studies that are a rough approximation of in vivo conditions. Two-dimensional NMR techniques were used to assign proton resonances, and interproton distances were estimated from the observed nuclear Overhauser effects (NOEs). The experimental distances were used as constraints in a molecular dynamics and simulated annealing protocol using the modeling package DISCOVER to generate three-dimensional structures of the two agonists and two antagonists when present in a membrane-model environment to determine possible prebinding ligand conformations. It was determined that (1) NKA is helical from residues 6 to 9, with an extended N-terminus; (2) NKB is helical from residues 4 to 10, with an extended N-terminus; (3) [d-Pro2,d-Phe7,d-Trp9]SP has poorly defined helical properties in the midregion and a beta-turn structure in the C-terminus (residues 6-9); and (4) [d-Arg1,d-Pro2, d-Phe7,d-His9]SP has a helical structure in the midregion (residues 4-6) and a well-defined beta-turn structure in the C-terminus (residues 6-10). Attempts have been made to correlate the observed conformational differences between the agonists and antagonists to their binding potencies and biological activity.


Complete occlusion of the left main coronary artery and the importance of coronary collateral circulation.
Study of four patients who survived complete occlusion of the left main coronary artery forms the basis of conclusions concerning the functional significance of coronary collateral circulation. Each of these patients had prominent collateral circulation from the right coronary artery. Global left ventricular function was maintained to the extent that congestive heart failure did not occur; the biplane ejection fraction was normal in the two patients where measurement was possible. The peak rate of systolic wall thickening by roentgen videometry in anterior left ventricular segments was normal in one patient and mild to moderately depressed in another. Experience with the patients described herein indicates that coronary collateral flow can provide critically needed circulatory support for the patient with coronary artery disease.


[EVI1 and its role in myelodysplastic syndrome, myeloid leukemia and other malignant diseases].
The ecotropic viral integration site 1 (EVI1) gene was identified as a common locus of retroviral integration in myeloid tumors found in mice. EVI1 gene is highly conserved through evolution and human gene EVI1 on chromosome 3q26 encodes zinc fingers-containing transcription factor. EVI1 is expressed in nonhematopoietic tissues but not in normal blood or bone marrow. EVI1 was detected in hematopoietic cells in retrovirus-induced myeloid leukemias in mice and several reports documented EVI1 expression in human myelodysplastic syndromes and other hematologic malignancies without 3q26 translocations. EVI1 is abnormally expressed in human myeloid leukemias that are associated with the t(3;3)(q21;q26), t(3;21)(q26;q22), inv(3)(q21q26) and other chromosomal rearrangements. EVI1 is overexpressed in some ovarian cancers and human colon cancer cell lines and may play a role in the initiation and/or progression of solid tumors, as well as hematopoietic malignancies. EVI1 is a transcriptional repressor which inhibits transforming growth factor beta (TGFbeta) family signalling by binding signal transducers (Smad proteins) and recruiting transcriptional corepressors. TGFbeta is an important regulator of proliferation, differentiation, apoptosis and migration of cells. EVI1 inhibits TGFbeta-mediated apoptosis. Knockdown of EVI1 function by small interference RNA increases the sensitivity of malignant cells to TGFbeta-mediated or other inducer-mediated apoptosis. Overexpressed EVI-1 blocks granulocyte and erythroid differentiation and possess the ability of growth promotion in some types of cells. EVI1 functions in some cases as a transcriptional activator which stimulates for example GATA2 and GATA3 promoters. The study of EVI1 target genes will help to clear the mechanism by which EVI1 upregulates cell proliferation, impairs cell differentiation, and induces cell transformation.


In-silico prediction, characterization, molecular docking and dynamic simulation studies for screening potential fungicides against leaf rust of Triticum aestivum.
Triticum aestivum is an important crop worldwide, which is a large source of food grain. T.aestivum demands on developed countries will grow every year, this increase in the demand is profoundly serious especially in the light climate change which would lead to a 29% reduction in final productivity. Rust fungus attacks the T.aestivum, specifically newly planted T.aestivum plants, which block the vascular system, stun, and finally damage grain and tillers. In present study we predict the 3D structure then find the binding pocket and conserved domains for MAPkinase-1 of Puccinia triticina. After that, screen the FungiPAD, PubChem, NPAtlas databases by physicochemical properties, docking, clustering, ADME (Absorption, distribution, metabolism, and excretion) and PAINS (pan assay interference compounds) filter analysis. Through this screening process screen the nine compounds, which are benzovindiflupyr, furametpyr, isopyrazam, fenaminstrobin, and flumorph from Fungicide database: zoxamide, vinclozolin, pentachloronitrobenzene, and dithianon from PubChem database, based on the binding energy, clustering, ADME and PAINS analysis. All these nine compounds bind in the same pocket and show the same pattern of interaction. Among these nine compounds, select the two compounds (PubChem:122087 (-6.96 kcal/mol) and FDBD02904 (-8.62 kcal/mol)) based on binding energy for 100 ns MD simulation and free energy calculation. MD simulation shows stability throughout the simulation, and it shows the sable interaction when compounds bind to the MAPKinase 1 protein which may help to protein kinase pathways in plant defense response. This result helps to design alternative fungicide against the wheat rust disease.Communicated by Ramaswamy H. Sarma.


Peculiarities of Alteromonas macleodii strains reflects their deep/surface habitation rather than geographical distribution.
The phenotypic, chemotaxonomic and genetic peculiarities of 5 deep strains of Alteromonas macleodii (isolated from Adriatic and Ionian Sea water from a depth of 1,000-3,500 m) and 5 strains of the same species isolated from the surface layer of Aegean, Andaman, Black Sea and Atlantic Ocean water near the British shore have been studied. Electron microscopy has shown that the deep strains' cells were, on average, two times longer (2.1±0.2×0.7±0.1 µm) than the surface strains' (1.1±0.1×0.6±0.1 µm). Using fatty acid analysis (particularly the mono-unsaturated C16:1 and C18:1 fatty acids contents) the deep and surface isolates were clearly separated into two clusters. Distinctions between them were also found in different lectin binding capacity, which is probably determined by the structure of their extracellular polysaccharide matrix. Analysis of the results of PCR with primers to repeated nucleotide sequences revealed a higher level of genetic polymorphism in surface strains in comparison with the deep isolates. This division was confirmed by the cluster analysis method though it was not as clear as in the fatty acids analysis. The described peculiarities are probably reflective of specific conditions in which A. macleodii strains live on the surface or in the depth of the world's oceans.


Childhood Idiopathic Steroid Resistant Nephrotic Syndrome, Different Drugs And Outcome.
The management of steroid resistant nephrotic syndrome (SRNS) is quite difficult in paediatric patients. Not only the remission is difficult but also these patients are at risk of progression to end stage renal disease (ESRD). The goal of treatment is either to achieve complete remission or even partial remission as it is the most important predictor of disease outcome. This study was conducted at The Children's Hospital, Lahore from February 2014 to May 2015. The SRNS patients of either sex between ages of 1-12 years were included with histology showing mesangioproliferative glomerulonephritis (MesangioPGN), focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Patients were given different immunosuppressant drugs and steroid 30 mg/m2 alternate day therapy on case to case basis and kept on regular follow up to check for response and adverse effects. Total of 105 patients included, 63 (60%) male and 42 (40%) female patients. The age ranges from 1.08 to 12 years, mean age of 6.53 years and SD of ±3.17. Tacrolimus was the most common drug used 43 (41%) patients followed by cyclosporine in 38 (36.2%) patients, while Mycophenolate mofetil (MMF) was prescribed in 21 (20%) patients. Complete response was in 96 (91.4%) initially while partial response was seen in 8 (7.6%) patients. On follow up, 92 (87.6%) patients showed complete response and partial response was in 5 (4.7%) patients. Cushingoid features and hypertrichosis were the most common adverse effect seen. Steroid resistant nephrotic syndrome can be managed well with various immunosuppressant drugs and steroids but treatment should be individualized according to clinical presentation, disease histology and cost/social factors.


A rare neoplasm of the thyroid gland.
Burkitt's lymphoma of the thyroid gland is a rare malignancy. We present a case of a 58-year-old female who developed a rapid enlargement of her thyroid gland. Core biopsy confirmed the diagnosis of Burkitt's lymphoma. The tumour resolved after three cycles of chemotherapy. This case report emphasises the importance of considering lymphoma when dealing with thyroid nodules and goitres, as its management is different from that of other thyroid pathologies and delaying treatment has an impact on prognosis.


Motility occurring in association with the surface of the Chlamydomonas flagellum.
Chlamydomonas flagella exhibit a previously undescribed form of motility. This is the rapid, bidirectional, saltatory movement of marker particles occurring in association with the extracellular surface of the flagellum.


Conditioned breathing depression during neonatal life as a function of associating ethanol odor and the drug's intoxicating effects.
Fetal and neonatal ethanol-related alterations upon the respiratory system have been described in different mammals. Studies also indicate that perinates learn about the sensory attributes of ethanol and associate them with diverse physiological effects of the state of intoxication. The present study was conducted in rat neonates during a developmental stage equivalent to the third human gestational trimester. The major goal was to analyze the consequences of ethanol odor exposure, the state of intoxication, or the temporal contiguity between these factors upon breathing patterns. The main findings were as follows: (a) a conditioned breathing depression was observed following few trials defined by the association between ethanol odor and the state of intoxication and (b) sequential exposure to ethanol sensitizes the organism to the drug's respiratory depressant effects without affecting ethanol metabolism. These results indicate that early breathing disruptions caused by ethanol can be determined or modulated via learning processes. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:670-686, 2016.


A cluster randomised, controlled trial of the value of dental health educators in general dental practice.
To test the effectiveness of dental health educators in general dental practice. To evaluate the effectiveness and cost of primary care trusts seconding dental health educators free of charge to suitable general dental practices to provide dental health counselling to mothers of regularly attending pre-school children at risk to caries. Two-cell, parallel group, cluster randomised, controlled clinical trial of two years' duration. 30 general dental practices in North-West England. 269 mothers of 334 pre-school children. Those in the test group were given visits to a dental health educator over a 2-year period to counsel mothers of at-risk, pre-school children. The rest were held as a control. Caries prevalence of the children and dental health knowledge, attitudes and toothbrushing skills of the parents. The full costs of the exercise were kept throughout. The statistical analysis controlled for the clustering of children within practices. After 2 years, 271 (81%) children and 248 (92%) mothers remained in the study. There was an 18% difference in mean dmft between the groups in favour of the test group children but this was not statistically significant. At the end of the study there was an 18% difference in mean dmft between the groups in favour of the test group children but this was not statistically significant. No difference in plaque levels was found. The mothers in the test group were more knowledgeable, had better attitudes towards the dental health of their offspring and better toothbrushing skills than those in the control. Each 2-hour session to counsel ten parents cost pound 40. Primary care trusts should carefully consider the cost value of seconding dental health educators to counsel parents of regularly attending, at-risk, pre-school children when considering such an option.


A review of active learning approaches to experimental design for uncovering biological networks.
Various types of biological knowledge describe networks of interactions among elementary entities. For example, transcriptional regulatory networks consist of interactions among proteins and genes. Current knowledge about the exact structure of such networks is highly incomplete, and laboratory experiments that manipulate the entities involved are conducted to test hypotheses about these networks. In recent years, various automated approaches to experiment selection have been proposed. Many of these approaches can be characterized as active machine learning algorithms. Active learning is an iterative process in which a model is learned from data, hypotheses are generated from the model to propose informative experiments, and the experiments yield new data that is used to update the model. This review describes the various models, experiment selection strategies, validation techniques, and successful applications described in the literature; highlights common themes and notable distinctions among methods; and identifies likely directions of future research and open problems in the area.


Elimination of human enteric viruses during conventional waste water treatment by activated sludge.
The present study was undertaken to determine if viruses were selectively eliminated during waste water treatment. Human enteric viruses were detected at all steps of treatment in a conventional activated sludge waste water treatment plant. Liquid overlays and large volume sampling with multiple passages on BGM cells permitted the detection of poliovirus (serotypes 1, 2, and 3), coxsackievirus B (serotypes 1, 2, 3, 4, and 5), and echovirus (serotypes 3, 14, and 22), as well as reoviruses. The mean virus concentration was 95.1 most probable number of infectious units per litre (mpniu/L) in raw sewage, 23.3 in settled water, 1.4 in effluent after activated sludge treatment, and 40.3 mpniu/L in sludge samples. All samples of raw sewage and settled water, 79% of effluent water, and 94% of sludge samples contained viruses. The mean reduction was 75% after settling and 98% after activated sludge treatment. Poliovirus type 3 was rarely isolated after the activated sludge treatment, but was still detected in about one-third of the sludge samples. Reoviruses and coxsackieviruses were detected at similar rates from all samples and appear to be more resistant to the activated sludge treatment than poliovirus type 3. Poliovirus types 1 and 2 were present in almost every sample of raw sewage and settled water and still found in about half of the effluent and sludge samples, indicating a level of resistance similar to that of reoviruses and coxsackieviruses.


Ulnar Neck Fractures Associated with Distal Radius Fractures.
Background There is little published data to guide management of ulnar neck fractures associated with fractures of the distal radius. Purpose As unplanned surgery usually reflects adverse events and this injury combination is relatively uncommon, we used a large database to study the incidence of unplanned surgeries after surgical and nonsurgical treatment of distal metaphyseal ulna fractures associated with a distal radius fracture and identify factors associated with these unplanned surgeries. Patients and Methods We identified 277 patients with an ulnar neck fracture associated with a distal radius fracture. Fifty-six (20%) ulnar neck fractures were initially treated operatively and six of them (11%) had a second, unplanned surgery. Of the 221 initially nonoperatively treated fractures, only one (0.45%) had a subsequent unplanned surgery that seemed unrelated to the fracture (ulnar nerve neurolysis). Results Bivariate analysis showed that younger age, open fracture, multifragmentary fractures, and initial operative treatment of the ulnar neck fracture were significantly associated with unplanned surgery. A multivariable analysis was not feasible due to the small number of unplanned surgeries. Conclusion Eighty percent of ulnar neck fractures associated with a fracture of the distal radius was treated nonoperatively in our region, and subsequent surgery for problems was very uncommon. Operative treatment and fracture complexity were associated with unplanned surgery, which reflected some measure of injury severity, technical inadequacy, and inherent problems associated with surgery. Level of Evidence Level II, prognostic study.


The use of clonidine in detoxification from opiates.
Use of clonidine hydrochloride in detoxification from opiates has demonstrated that this substance can rapidly suppress the signs and symptoms associated with opiate withdrawal. Clonidine hydrochloride, an alpha-adrenergic agonist, is a non-opiate substance. Studies to date indicate that clonidine is useful for withdrawal from methadone maintenance, where it can help in detoxifying the patient in less than 14 days (instead of the usual three to six months) with a high rate of success in achieving zero dosage. The results of a clinical investigation of clonidine are presented and discussed in this paper. It has been shown to suppress signs and symptoms of opiate withdrawal in patients taking up to 75 mg of methadone daily. Shorter-acting narcotics may be withdrawn in less than a week. To prevent relapse, post-detoxification counselling and the use of the narcotic antagonist, naltrexone, are recommended.


Assessment of care problems in Romania: feasibility and exploration.
The objective of this study was to study the feasibility of a recently developed instrument, LPZ-International, which assesses care problems in health care, and to describe the prevalence of care problems in Romanian health care institutions. Large differences exist in care services in Europe. Data on quality of care are absent or incomplete in Central-Eastern European countries. These countries, including Romania, have faced dramatic socioeconomic changes, which led to negative changes in quality of care. Cross-sectional study. Hospital wards, mental care institutions, and nursing homes. Nine health care institutions and admitted 394 patients. LPZ-International was introduced in 9 health care institutions in Romania. Assessed care problems included pressure ulcers, urinary and fecal incontinence, malnutrition, falls, and physical restraints. The data were collected between November 2013 and March 2014. Two health care professionals completed the questionnaire by hand at the patient's site. Six of the 9 health care institutions and 90% of the patients participated, which indicates the feasibility of LPZ-International, as did the completeness of the questionnaire. The data showed a high consistency and only a few were missing. The most frequent care problem was urinary and fecal incontinence, especially in the nursing home. Pressure ulcers and malnutrition were less frequent care problems in Romanian patients. Physical restraints were frequently applied in the nursing home and geriatrics and oncology wards. LPZ-International is a feasible instrument to assess care problems. The differences between wards and countries in the prevalence of care problems indicate differences in quality of care and the need for high-quality, comparative research.


THE RESPONSE OF THE ISOLATED SKIN OF RATS TO DRUGS AND ELECTRICAL STIMULATION.
A new method of transmural stimulation (Hellmann, 1963b) has been used to examine the responses of the rat panniculus carnosus, a skeletal muscle which lines the skin. This preparation responded to drugs and to electrical excitation in the same way as other mammalian skeletal muscle preparations. The relaxation phase, when examined with fast recording systems, was complicated by what appeared to be the "tone" of the muscle.


[Assessment of the protein quota in the ration of patients with the nephrotic syndrome according to balance studies].
From data derived from equilibrium investigations in patients with the nephrotic syndrome a negative nitrous balance which indicates the presence of a chronic protein deficiency developing in the organism of these patients was revealed. Observations showed that an increased quota of protein in the ration of patients with the nephrotic syndrome is quite justifiable. The quantity of protein comprising 1.5--2 g per kg of the patient's body weight per day, of which 3/4 is protein of animal origin, is optimal for this category of patients. Possible improvement of the protein supply in patients with the nephrotic syndrome is largely determined also by the qualitative composition of the protein in the ration.


Ion chromatography with suppressed conductivity detection: recoveries of 14C-labeled metabolites.
Suppressed conductivity detection, developed for use with ion chromatography, might be useful to assay specific activities of organic acids after metabolic labeling. Because the suppressor reduces background conductivity by acid-base neutralization and removal of ions from the eluent, it could influence recoveries and apparent retention times of labeled compounds. Elution times of 14C-labeled glucose and neutral amino acids, compounds not detected by conductivity, from the analytical column were found to be similar to those of lactate and acetate. When the suppressor was connected to the HPLC system in the recycle mode, the apparent elution times of amino acids increased and various organic acid fractions would be contaminated. When the suppressor was used in the external water mode, the labeled neutral amino acids and portions of acidic amino acids were recovered in the waste fraction; this indicated that recoveries of total 14C in the analyte fraction would be incomplete if the loss were not taken into account. Thus, the procedure to insert the suppressor into the system influences the apparent retention times and the recoveries of labeled amino acids in the analyte fraction; labeled metabolites not detected by conductivity can cause serious errors in specific activities of organic acids and should be removed from the sample prior to analysis.


[Sexually transmitted infections: update 2013].
Although there have been significant advances in diagnosis, treatment, and education, the occurence of STI continues to increase worldwide as well as in Switzerland. The most common STI include human papillomavirus (HPV), chlamydia, herpes, simplex virus types 1 and 2, gonorrhea, syphilis, hepatitis B and trichomoniasis. Diagnosis and treatment continue to be major public health challenges because of the asymptomatic nature of many of these infections. Recent studies showed favorable epidemiologic trends for HPV infection in vaccinated females as well as in some males. On the other hand we are confronted with rising incidences e.g. in urethritis with various causative agents and in syphilis cases. Alarmingly during the last 3 years gonococci have become less susceptible to our remaining antibiotics, necessitating strict adherence to updated treatment guidelines. Other trends in STIs and their consequences are discussed.


New world cutaneous leishmaniasis.
A 24-year-old Bangladeshi man presented with a 12-week history of a pruritic papule on his left elbow that had enlarged and ulcerated. He was without any constitutional or systemic symptoms. He reported a history of extensive travel in the two years prior to presentation that included Bangladesh, South and Central America, and Mexico. Histopathologic features were consistent with leishmaniasis. Speciation by the Centers for Disease Control showed L. brasiliensis.


Heavy inertial particles in rotating turbulence: Distribution of particles in flow and evolution of Lagrangian trajectories.
We revisit the problem of heavy particles suspended in homogeneous box turbulence flow subjected to rotation along the vertical axis, which introduces anisotropy along the vertical and horizontal planes. We investigate the effects of the emergent structures due to rotation, on the spatial distribution and temporal statistics of the particles. The distribution of particles in the flow are studied using the joint probability distribution function (JPDFs) of the second and third principle invariants of the velocity gradient tensor, Q and R. At high rotation rates, the JPDFs of Lagrangian Q-R plots show remarkable deviations from the well-known teardrop shape. The cumulative probability distribution functions for times during which a particle remains in vortical or straining regions show exponentially decaying tails except for the deviations at the highest rotation rate. The average residence times of the particles in vortical and straining regions are also affected considerably due to the addition of rotation. Furthermore, we compute the temporal velocity autocorrelation and connect it to the Lagrangian anisotropy in presence of rotation. The spatial and temporal statistics of the particles are determined by a complex competition between the rotation rate and inertia of the particle.


Functional electrical stimulation in spinal cord injury respiratory care.
The management of chronic respiratory insufficiency and/or long-term inability to breathe independently has traditionally been via positive-pressure ventilation through a mechanical ventilator. Although life-sustaining, it is associated with limitations of function, lack of independence, decreased quality of life, sleep disturbance, and increased risk for infections. In addition, its mechanical and electronic complexity requires full understanding of the possible malfunctions by patients and caregivers. Ventilator-associated pneumonia, tracheal injury, and equipment malfunction account for common complications of prolonged ventilation, and respiratory infections are the most common cause of death in spinal cord-injured patients. The development of functional electric stimulation (FES) as an alternative to mechanical ventilation has been motivated by a goal to improve the quality of life of affected individuals. In this article, we will review the physiology, types, characteristics, risks and benefits, surgical techniques, and complications of the 2 commercially available FES strategies - phrenic nerve pacing (PNP) and diaphragm motor point pacing (DMPP).


[Tarsal Kink: Pathognomonic Presentation and Therapy of a Rare Congenital Upper Eyelid Malformation].
Presentation of a congenital abnormality that is rare, but follows a distinct course and can be diagnosed and cured promptly if the pathognomonic presentation is recognized. A congenital tarsal kink leads to a malposition of the upper eyelid margin that must not be missed, as it will lead to ulcerative keratitis if it is not treated. An otherwise healthy newborn was presented after delivery with forceps with marked unilateral purulent secretion and blepharospasm. Neonatal dacryocystitis, gonococcal infection, congenital entropion with ulcerative keratitis, tarsal kink. It was not possible to fully examine the lid and cornea with the baby awake. Due to total inversion of the lid margin, no lashes could be seen. Under general anesthesia, the tarsal kink, with complete inversion of the lid margin and a corneal ulcer, was confirmed. The literature offers several methods to correct this rare malposition, all of which aim to strengthen the anterior lamella to correct the kink. After incision of the kink and repositioning of the tarsus and securing the position with fixation sutures, the ulcer healed quickly and completely; lid closure and lid contour were normal and symmetrical. Complete inversion of the lid margin is the pathognomonic sign of tarsal kink, giving the impression of "missing" lashes, accompanied by blepharospasm, followed by purulent secretion and corneal ulceration. The condition must not be misdiagnosed as only immediate correction can prevent severe damage.