[The location of the superficial peroneal nerve in the leg and its relation to the surgical approach of the fibula].
To localize the superficial peroneal nerve in surface of the leg and to provide a safety surgical approach to the fibula. Sixty-six adult legs preserved by 4% formaldehyde solution were studied involving 42 male and 24 female with the average age of 69 years old ranging from 37 to 88 years. There were 35 cases in left and 31 in right. According to the common lateral surgical approach to the fibula, the superficial peroneal nerve and its branches were dissected in 66 embalmed leg-ankle-foot specimens. The specimens were observed and measured. The superficial peroneal nerve branched from the common peroneal nerve near the anterolateral aspect of the neck of the fibula, transversing through the muscle, deep fascia and superficial fascia. In 12 cases of specimens, superficial fibular nerve extended to the foot with no branches, in 50 cases of specimens it branched out into two before piercing the deep fascia, in the rest 4 cases of specimens, it branched out into two before piercing the muscle. To avoid injuring the superficial peroneal nerve, the surgical approach to the 2/3 upper part of the fibula is at posterior crural septum, to the 1/3 lower part of the fibula is at anterior crural septum.


Comprehensive Longitudinal Microbiome Analysis of the Chicken Cecum Reveals a Shift From Competitive to Environmental Drivers and a Window of Opportunity for Campylobacter.
Chickens are a key food source for humans yet their microbiome contains bacteria that can be pathogenic to humans, and indeed potentially to chickens themselves. Campylobacter is present within the chicken gut and is the leading cause of bacterial foodborne gastroenteritis within humans worldwide. Infection can lead to secondary sequelae such as Guillain-Barré syndrome and stunted growth in children from low-resource areas. Despite the global health impact and economic burden of Campylobacter, how and when Campylobacter appears within chickens remains unclear. The lack of day to day microbiome data with replicates, relevant metadata, and a lack of natural infection studies have delayed our understanding of the chicken gut microbiome and Campylobacter. Here, we performed a comprehensive day to day microbiome analysis of the chicken cecum from day 3 to 35 (12 replicates each day; final n = 379). We combined metadata such as chicken weight and feed conversion rates to investigate what the driving forces are for the microbial changes within the chicken gut over time, and how this relates to Campylobacter appearance within a natural habitat setting. We found a rapidly increasing microbial diversity up to day 12 with variation observed both in terms of genera and abundance, before a stabilization of the microbial diversity after day 20. In particular, we identified a shift from competitive to environmental drivers of microbial community from days 12 to 20 creating a window of opportunity whereby Campylobacter can appear. Campylobacter was identified at day 16 which was 1 day after the most substantial changes in metabolic profiles observed. In addition, microbial variation over time is most likely influenced by the diet of the chickens whereby significant shifts in OTU abundances and beta dispersion of samples often corresponded with changes in feed. This study is unique in comparison to the most recent studies as neither sampling was sporadic nor Campylobacter was artificially introduced, thus the experiments were performed in a natural setting. We believe that our findings can be useful for future intervention strategies and help reduce the burden of Campylobacter within the food chain.


Relationship between Sympathetic Skin Responses and Auditory Hypersensitivity to Different Auditory Stimuli.
[Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli.


Functional plasticity of regenerated and intact taste receptors in adult rats unmasked by dietary sodium restriction.
Unilateral chorda tympani nerve sectioning was combined with institution of a sodium-restricted diet in adult rats to determine the role that environment has on the functional properties of regenerating taste receptor cells. Rats receiving chorda tympani sectioning but no dietary manipulation (cut controls) and rats receiving only the dietary manipulation (diet controls) had normal responses to a concentration series of NaCl, sodium acetate (NaAc), and NH4Cl. However, responses from the regenerated nerve in NaCl-restricted rats (40-120 d postsectioning) to NaCl and NaAc were reduced by as much as 30% compared to controls, indicating that regenerating taste receptors are influenced by environmental (dietary) factors. Responses to NH4Cl were normal; therefore, the effect appears specific to sodium salts. Surprisingly, in the same rats, NaCl responses from the contralateral, intact chorda tympani were up to 40% greater than controls. Thus, in the same rat, there was over a twofold difference in sodium responses between the right and left chorda tympani nerves. A study of the time course of the functional alterations in the intact nerve revealed that responses to NaCl were extremely low immediately following sectioning (about 20% of the normal response), and then increased monotonically during the following 50 d until relative response magnitudes became supersensitive. This function occurred even when the cut chorda tympani was prevented from reinnervating lingual epithelia, demonstrating that events related to regeneration do not play a role in the functional properties of the contralateral side of the tongue.(ABSTRACT TRUNCATED AT 250 WORDS)


Cutaneous CD30-positive T-cell lymphoproliferative disorders-clinical and histopathologic features, differential diagnosis, and treatment.
Cutaneous CD30+ T-cell lymphoproliferative disorders (CD30+ LPD) are the second most common form of cutaneous T-cell lymphoma. CD30+ LPD include lymphomatoid papulosis, primary cutaneous anaplastic large-cell lymphoma, and borderline lesions. Despite expression of CD30 by the neoplastic cells as the hallmark of these disorders, they differ in their clinical presentation and histological features as well as the course, the prognosis, and consecutively in the treatment. Diagnosis of CD30+ LPD and distinction from the broad spectrum of differential diagnoses essentially depends on clinicopathologic correlation as well as the results of staging examinations. Although the histological findings indicate a high-grade lymphoma, CD30+ LPD in most cases have a favorable prognosis. Recent advances in targeted therapy have led to new therapeutic approaches to CD30+ LPDs. This review describes the clinicopathologic features of CD30+ LPDs, their differential diagnoses, the treatment, and the role of CD30 as a diagnostic marker and therapeutic target.


High risk, high reward: An analysis of outcomes for candidates awaiting hepatic re-transplantation.
Background. Liver re-transplantation (re-OLT) remains the only feasible option for patients with graft failure following liver transplantation. Sparse resources and a growing waitlist mandate that available grafts are allocated properly. We studied the differences in patient demographics, characteristics, and survival for those listed for re-OLT in a region with prolonged wait times. We performed a single-center retrospective study, from 2005 to 2013, of adult candidates listed for liver re-OLT at a tertiary care center within United Network for Organ Sharing (UNOS) region 1. Of the 48 patients listed for re-OLT, 1(2%) improved while waiting, 14(29%) died while waiting, and 33(69%) underwent re-OLT. Those re-transplanted represented 11% of the center's adult liver transplant volume during the same time period. Comparing those who died while waiting to those who achieved re-OLT, there was no significant difference in age (median 52 vs. 48 years, p=0.56) or MELD at second listing (median 29 vs. 26, p = 0.90). Waitlisted candidates who failed to achieve re-transplant died on average of 15.5 days (IQR 36 days) days after re-listing. Those re-transplanted achieved 3-year survival of 70% and there was no significant difference in 3-year survival of those re-transplanted within or beyond 90 days of first transplant (70% vs. 69.5%, p = 0.28). In conclusion, re-OLT is the only viable option for candidates with nonreversible liver graft failure. Inability to achieve re-OLT leads to nearly assured and expeditious death. Despite technical challenges, in experienced hands excellent long term survival following re-OLT can be achieved.


Principle of two-dimensional characterization of copolymers.
Two-dimensional polymer characterization is used for a simultaneous analysis of molar masses and chemical heterogeneities (e.g., end groups, copolymer composition, etc.). This principle is based on coupling of two different chromatographic modes. Liquid adsorption chromatography at critical conditions (LACCC) is applied for a separation according to the chemical heterogeneity, whereas in the second-dimension fractions are analyzed with regard to their molar mass distribution by means of size exclusion chromatography (SEC). Because appropriate standards for a calibration of the SEC are seldom available, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) was used to substitute the SEC. The LACCC-MALDI MS coupling enables acquiring additional structural information on copolymer composition, which can considerably enhance the performance of this coupled method.


Biodegradation and detoxification of bisphenol A with one newly-isolated strain Bacillus sp. GZB: kinetics, mechanism and estrogenic transition.
A facultative anaerobic bacterial strain, Bacillus sp. GZB, was isolated and identified to effectively degrade bisphenol A (BPA) under anaerobic and aerobic conditions. Under anaerobic condition, Fe(3+) can be used as an electron acceptor for Bacillus sp. GZB, while 5 mg L(-1) BPA can be fully removed and 51% was mineralized under optimal aerobic conditions. Additionally, seven metabolites were identified by GC-MS, four of which were doubly confirmed by authentic standards (two synthesized) and three of four initial degradation intermediates were also quantified during BPA aerobic degradation. The evolution of 1-(4-hydroxyphenyl)ethanone showed a similar tendency with estrogenic activity changing during BPA biodegradation course, indicating its potential estrogenicity. The estrogenicity temporary increase first and decline ultimately during BPA degradation revealing the GZB can effectively detoxify BPA as well as its estrogenic intermediates. This was the first study to report a facultative anaerobic strain can degrade BPA with or without of oxygen.


Management of the Solitary Pulmonary Nodule.
- Optimal management of the patient with a solitary pulmonary nodule entails early diagnosis and appropriate treatment for patients with malignant tumors, and minimization of unnecessary interventions and procedures for those with ultimately benign nodules. With the growing number of high-resolution imaging modalities and studies available, incidentally found solitary pulmonary nodules are an increasingly common occurrence. - To provide guidance to clinicians involved in the management of patients with a solitary pulmonary nodule, including aspects of risk stratification, workup, diagnosis, and management. - Data for this review were gathered from an extensive literature review on the topic. - Logical evaluation and management pathways for a patient with a solitary pulmonary nodule will allow providers to diagnose and treat individuals with early stage lung cancer and minimize morbidity from invasive procedures for patients with benign lesions.


The CTSA as an exemplar framework for developing multidisciplinary translational teams.
Translational science requires that scientists from multiple disciplines work together to improve the prevention, diagnosis, and treatment of human disease. Although a literature exists on the design and management of multidisciplinary teams, little has been written on multidisciplinary translational teams (MTTs). MTTs are distinct hybrid entities, with goals taken from both industry and academic models. We identified 30 design factors in 10 domains from a literature survey relevant to our MTT model: specific goals, structures, and processes. These dimensions were adapted to our own institutional environment in the selection and management of 11 MTTs that exploited resources of University of Texas Medical Branch (UTMB) Clinical and Translational Sciences Awards (CTSA). Case illustrations of two specific MTTs illustrate some of the challenges encountered and opportunities realized in terms of education and scientific advances. Network depiction of disciplinarity indicated that CTSA KRs and CTSA leadership contributed to discipline diversity especially in small (or nascent) MTTs. A separate depiction of MTT-KR utilization indicated that data analysis, translational technologies, and novel methods were heavily utilized by MTTs, whereas other KRs contributed significant effort to infrastructure development. We conclude that the CTSA can provide a rich infrastructural framework and scientific environment for the development of successful MTTs.


Opportunity is the greatest barrier to providing palliative care to advanced colorectal cancer patients: a survey of oncology clinicians.
Palliative care (pc) is part of the recommended standard of care for patients with advanced cancer. Nevertheless, delivery of pc is inconsistent. Patients who could benefit from pc services are often referred late-or not at all. In planning for improvements to oncology pc practice in our health care system, we sought to identify barriers to the provision of earlier pc, as perceived by health care providers managing patients with metastatic colorectal cancer (mcrc). We used the Michie Theoretical Domains Framework (tdf) and Behaviour Change Wheel (bcw), together with knowledge of previously identified barriers, to develop a 31-question survey. The survey was distributed by e-mail to mcrc health care providers, including physicians, nurses, and allied staff. Responses were obtained from 57 providers (40% response rate). The most frequently cited barriers were opportunity-related-specifically, lack of time, of clinic space for consultations, and of access to specialist pc staff or services. Qualitative responses revealed that resource limitations varied by cancer centre location. In urban centres, time and space were key barriers. In rural areas, access to specialist pc was the main limiter. Self-perceived capability to manage pc needs was a barrier for 40% of physicians and 30% of nurses. Motivation was the greatest facilitator, with 89% of clinicians perceiving that patients benefit from pc. Based on the Michie tdf and bcw model, interventions that best address the identified barriers are enablement and environmental restructuring. Those findings are informing the development of an intervention plan to improve oncology pc practices in a publicly funded health care system.


Image-guided versus blind glucocorticoid injection for shoulder pain.
Traditionally, glucocorticoid injection for the treatment of shoulder pain has been performed guided by anatomical landmarks alone. With the advent of readily available imaging tools such as ultrasound, image-guided injections have increasingly become accepted into routine care. While there is some evidence that the use of imaging improves accuracy, it is unclear from current evidence whether or not it improves patient-relevant outcomes. The aim of this review was to assess whether image-guided glucocorticoid injections improve patient-relevant outcomes compared to landmark-guided or systemic intramuscular injections in patients with shoulder pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, via The Cochrane Library), MEDLINE (Ovid), and EMBASE (Ovid) to June 2011. We also searched the World Health Organisation International Clinical Trials Registry Platform (http://www.who.int/trialsearch/Default.aspx) to identify ongoing trials and screened reference lists of retrieved review articles and trials to identify potentially relevant studies. We included randomised controlled trials (RCTs) and quasi-randomised controlled clinical trials that compared image-guided glucocorticoid injection to landmark-guided or systemic intramuscular injection. Outcomes of interest included pain, function, range of motion, proportion of participants with overall improvement and adverse events. There were no restrictions on language or date of publication. Two review authors independently selected the studies for inclusion, extracted the data and performed a risk of bias assessment. Disagreement about inclusion or exclusion of individual studies and risk of bias was resolved by a third review author. Five studies (290 participants) were included in the review. The image-guided groups in all trials used ultrasound to guide injection. Four studies included participants with rotator cuff disease; in three the comparator was local landmarks to direct injection into the subacromial bursa and in the fourth the comparator was systemic intramuscular injection into the upper gluteal muscles in the buttock region. One study included participants with adhesive capsulitis and injection was directed into the glenohumeral joint by either ultrasound or anatomical landmark guidance.No significant differences between groups were observed with respect to reduction in pain at one to two weeks (two trials, 146 participants, standardized mean difference (SMD) -1.44, 95% CI -4.14 to 1.26), or function at one to two weeks (two trials, 146 participants, SMD 0.95, 95% confidence interval (CI) -1.29 to 3.20; back-translated to mean difference (MD) 4 points, 95% CI -5 to 13, on a 0 to 100 point scale, higher score means better function) or six weeks (three trials, 207 participants, SMD 0.63, 95% CI -0.06 to 1.33; back-translated to MD -3 points, 95% CI -11 to 5, on a 0 to 100 point scale) and the sensitivity analyses did not alter these results. While there was a significant difference between groups with respect to reduction in pain at six weeks favouring image guidance (three trials, 207 participants, SMD -0.80, 95% CI -1.46 to -0.14), there was considerable statistical heterogeneity and after removing trials with inadequate allocation concealment and inadequate blinding in a sensitivity analysis, the difference was no longer significant (one trial, 106 participants, MD -0.60 points, 95% CI -1.44 to 0.24 points on a 9-point scale).No statistical difference in adverse events between groups was identified (10/104 image-guided group versus 16/103 comparator; risk ratio (RR) 0.55, 95% CI 0.17 to 1.85). Minor adverse events reported included transient post-injection pain, facial redness and warmth. Based upon moderate evidence from five trials, our review was unable to establish any advantage in terms of pain, function, shoulder range of motion or safety, of ultrasound-guided glucocorticoid injection for shoulder disorders over either landmark-guided or intramuscular injection. The lack of any added benefit of ultrasound guided subacromial bursal injection over glucocorticoid injection administered into the upper gluteal muscles of the buttock suggests that the benefits of glucocorticoid may arise through systemic rather than local effects. Therefore, although ultrasound guidance may improve the accuracy of injection to the putative site of pathology in the shoulder, it is not clear that this improves its efficacy to justify the significant added cost.


Dietary Dihydromethysticin Increases Glucuronidation of 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol in A/J Mice, Potentially Enhancing Its Detoxification.
Effective chemopreventive agents are needed against lung cancer, the leading cause of cancer death. Results from our previous work showed that dietary dihydromethysticin (DHM) effectively blocked initiation of lung tumorigenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice, and it preferentially reduced 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)-derived DNA adducts in lung. This study explored the mechanism(s) responsible for DHM's differential effects on NNK/NNAL-derived DNA damage by quantifying their metabolites in A/J mice. The results showed that dietary DHM had no effect on NNK or NNAL abundance in vivo, indicating that DHM does not affect NNAL formation from NNK. DHM had a minimal effect on cytochrome P450 2A5 (CYP2A5, which catalyzes NNK and NNAL bioactivation in A/J mouse lung), suggesting that it does not inhibit NNAL bioactivation. Dietary DHM significantly increased O-glucuronidated NNAL (NNAL-O-gluc) in A/J mice. Lung and liver microsomes from dietary DHM-treated mice showed enhanced activities for NNAL O-glucuronidation. These results overall support the notion that dietary DHM treatment increases NNAL detoxification, potentially accounting for its chemopreventive efficacy against NNK-induced lung tumorigenesis in A/J mice. The ratio of urinary NNAL-O-gluc and free NNAL may serve as a biomarker to facilitate the clinical evaluation of DHM-based lung cancer chemopreventive agents.


[Alexander's disease in an adult].
A 34-year-old man developed cerebellar symptoms, palatal myoclonus and spastic paraparesis progressing over several months. During this period, acute respiratory failure occurred in two instances with evidence of central chronic hypoventilation. CT scan showed enlargement of the frontal horns and posterior fossa cisterns. Post mortem examination revealed the following features: 1) Rosenthal's fibers widespread throughout the CNS but especially in subependymal regions; 2) bilateral white matter cavitations involving the frontal lobes, hilum of dentate nuclei and bulbar pyramids; 3) microscopic pseudogliomatous foci present in several sites, especially in the fornix and midbrain tegmentum; 4) the medulla and high cervical spinal cord showed "peripheral type" myelin fibers along with Schwann cell proliferation in aberrant intra-parenchymal situation. The relationship of this case--as well as the few previous adult reports--to the well-defined infantile Alexander's disease is discussed. The possible hamartomatous nature of both glial changes and aberrant myelin production is emphasized. These various lesions, including Rosenthal fiber formation, are assumed to result from a similar--probably dysontogenetic--pathophysiological mechanism. It is suggested that Alexander's disease, in this case, should be classified among phakomatoses rather than enzymopathic leukodystrophies.


Integrated Transcriptomic and Translatomic Inquiry of the Role of Betaine on Lipid Metabolic Dysregulation Induced by a High-Fat Diet.
An excessive high-fat/energy diet is a major cause of obesity and linked complications, such as non-alcoholic fatty liver disease (NAFLD). Betaine has been shown to effectively improve hepatic lipid metabolism. However, the mechanistic basis for this improvement is largely unknown. Herein, integration of mRNA sequencing and ribosome footprints profiling (Ribo-seq) was used to investigate the means by which betaine alleviates liver lipid metabolic disorders induced by a high-fat diet. For the transcriptome, gene set enrichment analysis demonstrated betaine to reduce liver steatosis by up-regulation of fatty acid beta oxidation, lipid oxidation, and fatty acid catabolic processes. For the translatome, 574 differentially expressed genes were identified, 17 of which were associated with the NAFLD pathway. By combined analysis of transcriptome and translatome, we found that betaine had the greater effect on NAFLD at the translational level. Further, betaine decreased translational efficiency (TE) for IDI1, CYP51A1, TM7SF2, and APOA4, which are related to lipid biosynthesis. In summary, this study demonstrated betaine alleviating lipid metabolic dysfunction at the translational level. The transcriptome and translatome data integration approach used herein provides for a new understanding of the means by which to treat NAFLD.


Cold, Wind, and Sun Exposure: Managing-and Preventing-Skin Damage.
Outdoor athletes, through the course of their training and competition, are constantly battling environmental effects. Cold and wind exposure can lead to frostbite, which may not be immediately apparent if the skin grows numb. Other common cold-induced conditions include Raynaud's phenomenon, cold-induced urticaria, and chilblains. Summer athletes and athletes participating at higher altitudes need to be especially vigilant for sunburn. Physicians should know when to withhold athletes from play to prevent further damage. By teaching prevention strategies, clinicians can help their patients safely enjoy outdoor sports.


The pH dependence of the tetrodotoxin-blockade of the sodium channel and implications for toxin binding.
On the internally perfused, voltage-clamped squid giant axon, the effect of pH on the potency of tetrodotoxin in blocking the sodium current has been re-examined at pH 7.8 and 8.8. Confirming previous studies, tetrodotoxin is weaker at pH 8.8, when the deprotonated C-10 -OH makes the toxin molecule a zwitterion. In contrast to previous studies, our results, based on full dose--response relations, show that the relative potency at the two pH values appreciably exceeds the ratio of the abundance of the protonated C-10 form. In a medium of lowered ionic strength, tetrodotoxin is weaker, and the relative potency at pH 7.8 and 8.8 approaches the ratio of the relative abundance of the C-10 -OH. The results are believed to support hydrogen bonding at C-10 as a contributing factor in the binding of tetrodotoxin to the membrane receptor.


A spectrin-like protein from mouse brain membranes: phosphorylation of the 235,000-dalton subunit.
A mouse brain spectrin-like protein, which was an immunoreactive analogue of erythrocyte spectrin, has been isolated from demyelinated membranes. This spectrin analogue was a 10.5 S, 972,000 molecular weight (Mr) (alpha beta)2 tetramer containing subunits of 240,000 (alpha) and 235,000 (beta) Mr. We demonstrated that in vivo only the 235,000 Mr beta subunit of the mouse brain spectrin-like protein was phosphorylated, which was an analogous situation to mouse erythrocyte spectrin in which only the 220,000 Mr beta subunit was phosphorylated. Incubation of isolated membrane fractions with [gamma-32P]ATP +/- adenosine 3',5'-cyclic monophosphate (cAMP) indicated that mouse brain spectrin-like protein, mouse erythrocyte spectrin, and human erythrocyte spectrin's beta subunits were all phosphorylated in vitro by membrane-associated cAMP-independent protein kinases.


Clinical and morphologic features of B-cell small lymphocytic lymphoma with del(6)(q21q23).
Deletions of the long arm of chromosome 6 have been described in acute and chronic lymphocytic leukemia (ALL and CLL) and prolymphocytic leukemia (PLL), and have been associated with t(14;18)(q32;q21) in non-Hodgkin's lymphoma (NHL). Of 55 cases of small lymphocytic (sm lym) NHL, deletions of 6(q21q23) were the most common recurring cytogenetic abnormality. Among 14 sm lym NHL with del(6)(q21q23), this abnormality occurred as a solitary change in 3 cases. Each of these 3 cases, and 5 additional cases with del(6q) and other abnormalities, showed atypical larger forms with the morphologic appearance of prolymphocytes or paraimmunoblasts in the peripheral blood. In comparison, of the 11 cases without del(6q) and circulating abnormal cells, prolymphocytoid forms were observed in 4 cases (P < .001). Of the 31 sm lym without del(6q), trisomies of chromosomes 3, 12, or 18, or t(11;14)(q13;q32) occurred in greater than 10% of cases. Proliferation centers or infiltration by larger forms were observed in similar proportions of tissue sections derived from sm lym NHL with or without del(6q). The presence of the larger forms in the peripheral blood did not have an adverse prognostic impact on the survival of the del(6q) cohort, who experienced a median survival in excess of 6 years. All 14 cases of del(6q) sm lym NHL were characterized by a mature B-cell phenotype. Expression of CD11c, a feature of a CLL/PLL variant previously described, was not detected in 9 cases analyzed. In 5 cases of del(6q) sm lym NHL, no circulating abnormal lymphocytes were noted. Twelve cases presented with, or developed, clinical splenomegaly. These results suggest that deletion of a gene or genes at 6q21-23 is associated with the pathogenesis of a subset of B-cell sm lym NHL that may display larger prolymphocytoid cells in the peripheral blood, but that follows a clinical course typical of other well-differentiated lymphocytic neoplasms.


Candidatus Methanogranum caenicola: a novel methanogen from the anaerobic digested sludge, and proposal of Methanomassiliicoccaceae fam. nov. and Methanomassiliicoccales ord. nov., for a methanogenic lineage of the class Thermoplasmata.
The class Thermoplasmata harbors huge uncultured archaeal lineages at the order level, so-called Groups E2 and E3. A novel archaeon Kjm51a affiliated with Group E2 was enriched from anaerobic sludge in the present study. Clone library analysis of the archaeal 16S rRNA and mcrA genes confirmed a unique archaeal population in the enrichment culture. The 16S rRNA gene-based phylogeny revealed that the enriched archaeon Kjm51a formed a distinct cluster within Group E2 in the class Thermoplasmata together with Methanomassiliicoccus luminyensis B10(T) and environmental clone sequences derived from anaerobic digesters, bovine rumen, and landfill leachate. Archaeon Kjm51a showed 87.7% 16S rRNA gene sequence identity to the closest cultured species, M. luminyensis B10(T), indicating that archaeon Kjm51a might be phylogenetically novel at least at the genus level. In fluorescence in situ hybridization analysis, archaeon Kjm51a was observed as coccoid cells completely corresponding to the archaeal cells detected, although bacterial rod cells still coexisted. The growth of archaeon Kjm51a was dependent on the presence of methanol and yeast extract, and hydrogen and methane were produced in the enrichment culture. The addition of 2-bromo ethanesulfonate to the enrichment culture completely inhibited methane production and increased hydrogen concentration, which suggested that archaeon Kjm51a is a methanol-reducing hydrogenotrophic methanogen. Taken together, we propose the provisional taxonomic assignment, named Candidatus Methanogranum caenicola, for the enriched archaeon Kjm51a belonging to Group E2. We also propose to place the methanogenic lineage of the class Thermoplasmata in a novel order, Methanomassiliicoccales ord. nov.


Predicting Activity Duration in Smart Sensing Environments Using Synthetic Data and Partial Least Squares Regression: The Case of Dementia Patients.
The accurate recognition of activities is fundamental for following up on the health progress of people with dementia (PwD), thereby supporting subsequent diagnosis and treatments. When monitoring the activities of daily living (ADLs), it is feasible to detect behaviour patterns, parse out the disease evolution, and consequently provide effective and timely assistance. However, this task is affected by uncertainties derived from the differences in smart home configurations and the way in which each person undertakes the ADLs. One adjacent pathway is to train a supervised classification algorithm using large-sized datasets; nonetheless, obtaining real-world data is costly and characterized by a challenging recruiting research process. The resulting activity data is then small and may not capture each person's intrinsic properties. Simulation approaches have risen as an alternative efficient choice, but synthetic data can be significantly dissimilar compared to real data. Hence, this paper proposes the application of Partial Least Squares Regression (PLSR) to approximate the real activity duration of various ADLs based on synthetic observations. First, the real activity duration of each ADL is initially contrasted with the one derived from an intelligent environment simulator. Following this, different PLSR models were evaluated for estimating real activity duration based on synthetic variables. A case study including eight ADLs was considered to validate the proposed approach. The results revealed that simulated and real observations are significantly different in some ADLs (p-value < 0.05), nevertheless synthetic variables can be further modified to predict the real activity duration with high accuracy (R2(pred)>90%).


Cryptic gene pools in the Hypericum perforatum-H. maculatum complex: diploid persistence versus trapped polyploid melting.
In Central Europe Hypericum perforatum and Hypericum maculatum show significant hybridization and introgression as a consequence of Pleistocene range fluctuations, and their gene pools are merging on higher ploidy levels. This paper discusses whether polyploid hybrid gene pools are trapped in the ecological climatic niche space of their diploid ancestors, and tests the idea of geographical parthenogenesis. DNA sequence information of nuclear ribosomal DNA and plastid loci, ploidy level estimates and ecological niche modelling are used to characterize the various diploid and polyploid gene pools and unravel spatio-temporal patterns of gene flow among them. On the diploid level, the three gene pools are clearly distinct between and within species of H. perforatum (two gene pools) and H. maculatum, and their divergence dates back to the first half of the Pleistocene. All polyploids in Central Europe show high levels of past and contemporary gene flow between all three gene pools. The correlation of genetic and geographical distances breaks down if the latter is larger than 250 km, indicating recent and ongoing gene flow. The two species are ecologically differentiated, but in particular hybrids among all three gene pools do not show significant niche differences compared to their parental gene pools, except for some combinations with H. maculatum. Inter- and intraspecific gene flow between inter- and intra-species gene pools is limited on the diploid level, and the geographical distribution of the diploids largely reflects Pleistocene evolutionary history. Secondary contact promoted hybridization and introgression on the polyploid level, enabling offspring to escape the diploid gene pools. However, the hybrid polyploids do not show significant niche differences compared to their diploid progenitors. It is concluded that the observed absence of niche divergence has precluded further differentiation and geographical partitioning of new polyploid lineages being effectively separated from the parental lines. The predominantly apomictic reproducing polyploids are trapped in the polyploid gene pool and the ecological climatic niche space of their diploid ancestors.


Case for diagnosis.
Porokeratosis is a primary keratinizing disorder of unknown etiology. This disorder is characterized by the presence of centrifugally enlarging hyperkeratotic plaques, associated with the histopathological hallmark of cornoid lamellae. Genital porokeratosis is extremely rare. No more than thirty cases have been reported in the literature, including only one case of linear porokeratosis confined to the genital area. This case report describes a patient with genital linear porokeratosis, who was successfully treated with cryotherapy. Over two years of follow-up, the lesion improved and there was no evidence of recurrence or signs of malignant transformation. Nevertheless, there is a need for long-term follow-up data on recurrence and malignant transformation.


Antivascular therapy for multidrug-resistant ovarian tumors by macitentan, a dual endothelin receptor antagonist.
Endothelin receptors (ETRs) are often overexpressed in ovarian tumors, which can be resistant to conventional therapies. Thus, we investigated whether blockage of the ETR pathways using the dual ETR antagonist macitentan combined with taxol or cisplatinum can produce therapy for orthotopically growing multidrug-resistant (MDR) human ovarian carcinoma. In several studies, nude mice were injected in the peritoneal cavity with HeyA8-MDR human ovarian cancer cells. Ten days later, mice were randomized to receive vehicle (saline), macitentan (oral, daily), taxol (intraperitoneal, weekly), cisplatinum (intraperitoneal, weekly), macitentan plus taxol, or macitentan plus cisplatinum. Moribund mice were killed, and tumors were collected, weighed, and prepared for immunohistochemical analysis. The HeyA8-MDR tumors did not respond to taxol, cisplatinum, or macitentan administered as single agents. In contrast, combination therapy with macitentan and taxol or macitentan and cisplatinum significantly decreased the tumor incidence and weight and significantly increased the survival of mice and their general condition. Multiple immunohistochemical analyses revealed that treatment with macitentan and macitentan plus taxol or cisplatinum inhibited the phosphorylation of ETRs, decreased the levels of pVEGFR2, pAkt, and pMAPK in tumor cells after 2 weeks of treatment and induced a first wave of apoptosis in tumor-associated endothelial cells followed by apoptosis in surrounding tumor cells. Our study shows that ovarian cancer cells, which express the endothelin axis and are multidrug resistant, are exquisitely sensitive to treatment with a dual ET antagonist and can be resensitized to both taxol and cisplatinum. This combined therapy led to a significant reduction in tumor weight.


Urinary Neutrophil Gelatinase-Associated Lipocalin in Cirrhotic Patients with Acute Kidney Injury.
It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. The aim of the current work is to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis and to assess it as a prognostic marker. Out of 83 cirrhotic patients with AKI admitted between October 2015 and June 2016; 70 patients were included in this prospective study. Routine laboratory tests, uNGAL and fractional excretion of Na were obtained on admission. End points were death or improvement of kidney function and discharge. The patients included in our study were 41 males and 29 females with mean age 54.27 ± 6.08 years. HCV was the etiology of cirrhosis in 69 cases while one had combined HBV and HCV infection. More than 50% of patients were classified as Child C. Causes of kidney injury were prerenal, hepatorenal syndrome (HRS) and intrinsic tubular injury (iAKI) in 39 patients (55.7%), 17 patients (24.3%) and 14 patients (20%) respectively. mean value of uNGAL in prerenal, HRS and iAKI was 21.70 ± 7.31, 115.53 ± 68.19 and 240.83 ± 116.94 ng/mg creatinine respectively. MELD above 20 and uNGL above 32 were predictors of mortality. A single baseline measurement of uNGAL level has the ability to determine type of kidney dysfunction in cirrhotic patients, perhaps accelerating management decisions and improving outcomes.


D-Cycloserine: Agonist turned antagonist.
D-Cycloserine can enhance activation of the NMDA receptor complex and could enhance the induction of long-term potentiation (LTP). In animals and humans, D-cycloserine can enhance performance in learning and memory tasks. This enhancing effect can disappear during repeated administration. The enhancing effects are also lost when higher doses are used, and replaced by behavioral and biochemical effects like those produced by NMDA antagonists. It has been reported that NMDA agonists, applied before or after tetanic stimulation, can block the induction of LTP. This may be the result of feedback inhibition of second messenger pathways stimulated by receptor activation. This may explain the antagonist-like effects of glycine partial agonists like D-cycloserine. In clinical trials of D-cycloserine in age-associated memory impairment (AAMI) and Alzheimer's disease, chronic treatment provided few positive effects on learning and memory. This may be due to inhibition of second messenger pathways following chronic stimulation of the receptor complex.


Regulation of nitrobenzylthioninosine-sensitive adenosine uptake by cultured kidney cells.
The effect of nitrobenzylthioinosine (NBTI) on [3H]adenosine uptake and the characterization of the [3H]NBTI binding in cell (primary cultures and LLC-PK1 cell line) plasma membrane and brush-border membrane (BBM) vesicles from pig renal cortices and LLC-PK1 cells was analyzed. [3H]adenosine uptake was strongly inhibited by NBTI in nonconfluent cells, whereas it was totally insensitive to the reagent in BBM. The concentration dependence of [3H]adenosine uptake in BBM was linear, suggesting simple diffusion. In both cell membranes and BBM high-affinity [3H]NBTI binding was observed. [3H]NBTI binding as well as NBTI-sensitive [3H]adenosine uptake was strongly reduced when cells grew to confluence. Both reduction effects were reproduced by treatment of nonconfluent cells with chlorophenyl adenosine 3',5'-cyclic monophosphate (cAMP), which indicates that the transporter is regulated by a cAMP-dependent protein kinase. To confirm this hypothesis, the binding of [3H]NBTI was analyzed in pig kidney BBM obtained in the presence of orthovanadate and alkaline phosphatase. With respect to control membranes, BBM obtained in the presence of orthovanadate showed a lower maximum number of binding sites (Bmax), whereas those obtained in the presence of alkaline phosphatase showed a slight increase in Bmax for [3H]NBTI binding. Taken together, these results suggest that the reduction in both [3H]NBTI-binding capacity and NBTI-sensitive [3H]adenosine uptake takes place by a mechanism that involves phosphorylation of the transporter molecule or of a protein that interacts with it.


Preparation and characterization of monoclonal antibodies against nucleostemin, a protein that controls cell proliferation in stem cells and cancer cells.
Nucleostemin (NS) is a novel protein that promotes the proliferation of stem cells and cancer cells. The aim of this study is to prepare specific monoclonal antibodies against nucleostemin as a tool in nucleostemin research. To generate the antibodies, the cDNA coding nucleostemin was cloned from human gastric cancer cell line NCI-N87 with reverse transcriptase-polymerase chain reaction (RT-PCR). The partial cDNA fragment was inserted into prokaryotic expression vector pGEX-4T1 to make glutathione S-transferase (GST) fusion protein in Escherichia coli, and the whole-length cDNA fragment was cloned into vector pcDNA3 for expression in mammalian cells. The spleen cells, from the BALB/c mouse immunized with the GST-nucleostemin fusion protein, were used to prepare the monoclonal antibody with hybridoma technique. After screening with enzyme-linked immunosorbent assay (ELISA) and subcloning, six specific monoclonal antibodies against nucleostemin were obtained. Moreover, they also worked well in Western blotting, immunoprecipitation, and immunohistochemistry. These antibodies will be helpful in elucidating biological functions and the molecular mechanism of nucleostemin.


Trial design for cancer (cell)-specific anticancer therapies.
The last decade has brought a totally new class of systemic anticancer treatment options, the so-called cancer (cell)-specific (CCS) anticancer agents. Until recently, this treatment modality has been referred to as 'targeted therapy' but as all existing systemic anticancer therapies have a clearly defined target, this seems to be a misnomer. Despite impressive results of several CCS drugs, the present set up of drug development is ill suited for CCSs due to the nature of the majority of these compounds. The authors focus on specific aspects of how to design early clinical trials with this new class of anticancer agents with focus on pharmacodynamic behaviour in relation to response, optimal dose and treatment duration.


[Treatment of critical lower limb ischemia].
Critical limb ischemia is a major public health problem in our western countries due to the epidemia of (diabesity). The outcome of patients suffering from critical limb ischemia reains poor with an amputation free survival rate at one year of about 50%. The treatment should be multidiciplinary and done in emergency in specialized centers to ensure the limb salvage: this management should be centered aroud 3 axis: the screening of the cardiovascular risk factors, the best medical treatment and the invasive approaches. Due to multiple endovascular technical innovations, more frail patients with com plex diseases can be treated with good results. Therefore, the endovascular treatment is essential in the management of such patients by vascular surgeons.


Transitions between Andean and Amazonian centers of endemism in the radiation of some arboreal rodents.
The tropical Andes and Amazon are among the richest regions of endemism for mammals, and each has given rise to extensive in situ radiations. Various animal lineages have radiated ex situ after colonizing one of these regions from the other: Amazonian clades of dendrobatid frogs and passerine birds may have Andean ancestry, and transitions from the Amazon to Andes may be even more common. To examine biogeographic transitions between these regions, we investigated the evolutionary history of three clades of rodents in the family Echimyidae: bamboo rats (Dactylomys-Olallamys-Kannabateomys), spiny tree-rats (Mesomys-Lonchothrix), and brush-tailed rats (Isothrix). Each clade is distributed in both the Andes and Amazonia, and is more diverse in the lowlands. We used two mitochondrial (cyt-b and 12S) and three nuclear (GHR, vWF, and RAG1) markers to reconstruct their phylogenetic relationships. Tree topologies and ancestral geographic ranges were then used to determine whether Andean forms were basal to or derived from lowland radiations. Four biogeographic transitions are identified among the generic radiations. The bamboo rat clade unambiguously originated in the Amazon ca. 9 Ma, followed by either one early transition to the Andes (Olallamys) and a later move to the Amazon (Dactylomys), or two later shifts to the Andes (one in each genus). The Andean species of both Dactylomys and Isothrix are sister to their lowland species, raising the possibility that highland forms colonized the Amazon Basin. However, uncertainty in their reconstructed ancestral ranges obscures the origin of these transitions. The lone Andean species of Mesomys is confidently nested within the lowland radiation, thereby indicating an Amazon-to-Andes transition ca. 2 Ma. Differences in the timing of these biogeographic transitions do not appear to explain the different polarities of these trees. Instead, even within the radiation of a single family, both Andean and Amazonian centers of endemism appear enriched by lineages that originated in the other region. Our survey of other South American lineages suggests a pattern of reciprocal exchange between these regions-among mammals, birds, amphibians, and insects we found no fewer than 87 transitions between the Andes and Amazon from Miocene-Pleistocene. Because no clear trend emerges between the timing and polarity of transitions, or in their relative frequency, we suggest that reciprocal exchange between tropical highland and lowland faunas in South America has been a continual process since ca. 12 Ma.


Identification and characterization of a virus-inducible non-coding RNA in mouse brain.
Infection of mice with Japanese encephalitis virus or Rabies virus results in the activation of a gene encoding a novel, non-coding RNA (ncRNA) in the mouse central nervous system. This transcript, named virus-inducible ncRNA (VINC), is identical to a 3.18 kb transcript expressed in mouse neonate skin (GenBank accession no. AK028745) that, together with a number of unannotated cDNAs and expressed sequence tags, is grouped in the mouse unigene cluster Mm281895. VINC is expressed constitutively in early mouse embryo and several adult non-neuronal mouse tissues, as well as a murine renal adenocarcinoma (RAG) cell line. Northern blotting of nuclear and cytoplasmic RNAs revealed that VINC is localized primarily in the nucleus of RAG cells and is thus a novel member of the nuclear ncRNA family.


Myoblast differentiation during mammalian somitogenesis is dependent upon a community effect.
The differentiation potential of early mammalian myogenic cells was tested under clonal culture conditions. Cells were isolated from paraxial mesoderm and limb buds of transgenic mouse embryos at 9.5 days after conception and grown in culture at clonal density either on collagen-coated dishes or on various feeder cell layers. The transgene used contained a reporter gene encoding beta-galactosidase with a nuclear localization signal under the control of regulatory sequences from the gene for fast myosin light chain 3, so that beta-galactosidase staining indicated the presence of differentiated muscle cells. After 5 days in culture, the number and size of beta-galactosidase-positive (beta-gal+) clones were recorded. Cells isolated from somites I-V (the last five somites to have formed) or from unsegmented paraxial mesoderm did not give rise to any beta-gal+ clones. Cells isolated from somites VI-X or from the forelimb bud gave rise to beta-gal+ clones, but only on feeder cells. Cells from somites XI or older gave rise to beta-gal+ clones independently of the substrate. However, when cells isolated from unsegmented paraxial mesoderm or somites I-V were cultured with nontransgenic cells from the trunk (including neural tube and notochord), differentiation occurred on condition that the cells were in a three-dimensional aggregate, even though their specific position in the somite had been lost. By culturing explants ranging in size from 1 to < 100 cells in the presence of an inhibitor of cell division, we determined that a minimal number of 30-40 cells is required for mesodermal cells to differentiate.


Divergent reaction pathways of homologous and isosteric propargyl amides in sequential Ru/Pd-catalyzed annulations for the synthesis of heterocycles.
Cu-catalyzed three-component coupling of imines with benzoyl chloride and terminal arylalkynes followed by enyne ring-closing metathesis (RCM) and Heck cyclization afforded medicinally relevant benzoindolines, cyclopropane-fused indenopyridines, pyrroloquinolines, or 1,7-tetrahydrophenanthrolines via divergent cyclization pathways. Unexpectedly, the Pd-catalyzed cyclization of heterocyclic dienes proceeded via regiodivergent 5-exo or 6-endo pathways depending on the ring size (n = 1, 2) or the presence of isosteric groups (CH vs N). A one-pot protocol for the enyne-RCM/Heck annulation featuring a sequential addition of the Ru and Pd catalysts was developed maximizing the synthetic efficiency.


High-power potassium-titanyl-phosphate laser photoselective vaporization prostatectomy for symptomatic benign prostatic hyperplasia.
Potassium-titanyl-phosphate (KTP) laser photoselective vaporization prostatectomy (PVP) is a relatively new technology for the management of lower urinary-tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). We review our initial experience. We prospectively evaluated our initial 12-month experience with 80 W KTP laser PVP. All had American Urological Association symptom score (AUASS), American Society of Anesthesiologists (ASA) risk score, serum prostate-specific antigen (PSA), maximum flow rate (Qmax), and postvoid residual (PVR) determinations and transrectal ultrasonography. There were 160 consecutive patients identified, with a mean age of 69.7 years (range 34-88 yrs) and a mean ASA score of 2.4 (range 1-4). The mean prostate volume was 72.3 cm(3) (range 20.3-261 cm(3)), with a mean PSA level of 2.2 ng/mL (range 0.1-17.9 ng/mL). Mean laser time and energy usage were 33.4 minutes (range 4-165 min) and 99.0 kJ (range 11.3-524 kJ), respectively. All were outpatient procedures with 96 (60%) patients catheter-free at discharge. Twenty-eight patients need catheter drainage for 1 week. Urinary-tract infections developed in 13 patients. Fourteen patients had clinically insignificant hematuria for more than 1 week. Bladder neck contractures that necessitated intervention developed in three patients. Three patients had persistent urinary retention. No urethral strictures or urinary incontinence were noted. Mean AUASS decreased significantly from 23 to 13, 9, 8, 7, and 6 (P < 0.05) at 1, 4, 12, 24, and 52 weeks, respectively. Qmax and PVR values also showed statistically significant improvement. Our initial results demonstrate that KTP laser PVP is safe and effective for the management of LUTS secondary to BPH.


Factors associated with deaths among pulmonary tuberculosis patients: a case-control study with secondary data.
Tuberculosis remains an important public health problem in Brazil where over 100 000 new cases and 6000 deaths are reported every year. Current drug efficacy and wide availability should have curbed this toll. The goal was to study the factors associated with death in incident cases of pulmonary tuberculosis (PT) during treatment. This is a case-control study including all new cases of PT reported between 2000 and 2004; cases were patients who died of any cause and controls were those cured after initial PT treatment. Data analyses included unconditional multiple hierarchical logistic regression. A total of 313 502 new cases of tuberculosis were reported between 2000 and 2004; 224 355 (71.6%) were cured after initial treatment and 20 721 (6.6%) died during the surveillance follow-up. Over 82% of all cases were diagnosed with PT. After controlling for significant variables, the factors associated with a higher risk of death included gender (males: odds ratio (OR) 1.4; 95% confidence interval (CI) 1.33 to 1.47), age (<5 years of age: OR 1.90; 95% CI 1.51 to 2.38; 30-59 years: OR 2.78; 95% CI 2.61 to 2.97; over 60 years: OR 10.92; 95% CI 10.09 to 11.81), positive HIV serology (OR 10.59; 95% CI 9.76 to 11.48), alcoholism (OR 1.49; 95% CI 1.36 to 1.65), mental disorder (OR 1.80; 95% CI 1.43 to 2.27) and presence of additional lung pathology on chest x ray (OR 2.22; 95% CI 1.83 to 2.70). Protective variables included education (highest level: OR 0.67; 95% CI 0.63 to 0.70). Preventive interventions should target the most vulnerable patients, in particular the very young and the elderly, those infected with HIV and those presenting with a mental disorder or additional lung pathology.


Distinct mRNA expression of the highly homologous convertases PC5 and PACE4 in the rat brain and pituitary.
Posttranslational endoproteolysis is essential for the production of biologically active peptides from inactive precursors. Six kexin/substilisin-like endoproteases have been characterized in mammalian species. To understand the complex physiological functions of each convertase within a cellular context it is necessary to comprehensively define its tissue distribution and cohabitation with other members of the family. Previous studies demonstrated the distinct distribution of PC1, PC2, and furin mRNAs in the pituitary and brain, suggesting a unique function for each enzyme. In the present study, the mRNA tissue distributions of the two most recent and homologous members, PC5 and PACE4, were analyzed in rat pituitary and brain using in situ hybridization histochemistry. In the pituitary, the anterior lobe exhibited moderate levels of PC5 and high levels of PACE4 mRNAs. The intermediate lobe showed low levels of PC5 expression, while PACE4 mRNA levels were undetectable. PACE4 transcripts were detected throughout cells of the neural lobe suggesting expression in pituicytes. In the brain, PC5 expression was more restricted than PACE4. PC5 mRNA was detected only in neuronal cells, whereas PACE4 mRNA was expressed in both neuronal and glial cells. In areas that are rich in neuropeptides such as cortex, hippocampus, and hypothalamus, mRNA levels of PC5 were high but PACE4 were low or undetectable. In regions, such as the amygdaloid body and thalamus, distinct but complementary distributions of PC5 and PACE4 mRNAs were observed. The medial habenular and cerebellar Purkinje cells expressed very high levels of PACE4 mRNA. The present data strongly suggest unique tissue-specific functions of PC5 and PACE4.


[Early treatment of third degree burns of the entire hand].
Treatment and result of burned total hand was reported here in 4 hands (4 cases). According to the treatment and anatomical characteristics, burned hand was divided into 4 areas: dorsum of hand, dorsum of finger, thenar-wrist area and volar-digit area. The treatment of total hand in third degree burns included emergency escharotomy of hand and digits, early escharotomy and immediate skin grafting on the dorsum of hand, thenar-wrist and volar-digit area. But on the dorsum of digit area this sort of hand was often deepen to the phalangeal bones and joints. After healing of early graft, the exposed bones and joints were decorticated with immediate grafting on the fresh bone marrow surface and with the finger tip repair so as to preserve the length of digits. When the bone marrow surface grafting healed metallic finger splints were bent sequentially to functional position for 8 weeks in order to ankylosis of interphalangeal joints. Followed up 4 hands with good results. And only 5 distal phalanges were loss in 20 digits. But in previous cases this kinds of digits were often amputated with poor results.


Results of otovestibular tests in mild head injuries.
The neurotological workup of patients with minor head trauma was carried out prospectively. The preliminary results of the ongoing study were derived from 38 subjects (12 female, 26 male) at an average age of 33.5 years. All had been hospitalized after having suffered minimum head trauma followed by a temporary loss of consciousness, by amnesia, or by vomitting. The 38 subjects underwent the examination within 72 hours of the event and were summoned for a follow-up visit 3 months later. The anamnestic data show that the most frequent complaint was dizziness (81%). Tinnitus was noted in fewer than one-half of the patients, with a variety of descriptions. Twenty-six percent complained of hearing loss. The correlation between reported hearing loss and the finding on subsequent behavioral audiometry (within 72 hours after the event) was studied. The sensitivity of hearing loss (as complaint) was found to be only 40%, but its specificity was much higher at 83%. The overall equilibrium reflected in the composite score of the sensory testing in computed dynamic posturography actually worsened between tests. A good correlation was found between posturography results and symptomatology. We concluded that, after minor head trauma, most patients suffer from dizziness, and more than one-half complain of tinnitus or hearing loss. The unsteadiness does not subside within 3 months after concussion. A more protracted follow-up is required to summarize the outcome of head injury from a neurootological point of view. A clear correlation is found between complaints and posturography results. After minor head trauma, pure vestibular injuries are much less frequent than are central lesions. Motor dysfunction is less frequent than are the sensory abnormalities.


Distribution of galanin immunoreactivity in the respiratory tract of pig, guinea pig, rat, and dog.
Galanin, a newly discovered peptide isolated from porcine intestine, is known to cause contraction in rat smooth muscle preparations and to induce hyperglycaemia in dogs. By the use of radioimmunoassay and immunohistochemical techniques the concentration and distribution of galanin immunoreactivity were determined in several areas of the respiratory tract of five dogs, five guinea pigs, five rats, and two pigs. Antibodies were raised in rabbits to whole unconjugated natural porcine galanin. The highest galanin concentrations were found in the bronchus and the trachea of the dog, guinea pig, rat (2 pmol/g in each case), and pig (less than 1 pmol/g). The lowest galanin concentrations were found in the lung parenchyma. Gel chromatographic analysis in the pig showed one molecular form of galanin coeluting with the porcine galanin standard. By means of the indirect immunofluorescence technique on sections of tissues fixed in benzoquinone solution, galanin was found to be confined to nerve fibres in different regions of the respiratory tract. In the nasal mucosa of the pig nerve fibres containing galanin were distributed around seromucous glands and blood vessels and beneath the epithelium. In the trachea, bronchus, and major intrapulmonary airways of the pig, dog, and guinea pig galanin immunoreactive fibres were detected predominantly in smooth muscle, as well as around seromucous glands and in the adventitia of blood vessels. Rarely, galanin immunoreactive nerve fibres were found in the lung parenchyma. A few galanin immunoreactive ganglion cells also containing vasoactive intestinal polypeptide were found in the adventitia of the tracheobronchial wall of the pig and dog. The distribution of galanin suggests that it may have some influence on airway, vascular, and secretory functions in the mammalian respiratory tract.


Defects in peripheral oxygen utilization following trauma and shock.
Following shock and trauma, there may be capillary block or stasis that sets up a neurohumoral response, causing further capillary constriction and ischemia. This ischemia may not result in tissue hypoxia, as functioning capillaries may still exist near the damaged areas. Following resuscitation, however, a reperfusion syndrome causing massive tissue edema, endothelial swelling, and further capillary blocking may lead to tissue hypoxia. We used isolated canine hind limb as a model of the peripheral circulation in a series of experiments that showed that interstitial edema alone did not reproduce the defect in peripheral oxygen utilization. On the other hand, both reperfusion syndrome and microembolization were able to reproduce this response. Hypertonic mannitol and imidazole reversed this defect following either reperfusion syndrome or microembolization, respectively. These data suggest that resuscitated posttrauma patients suffering from defects in peripheral oxygen utilization probably owing to microembolization, reperfusion and tissue edema, which may be treated by specific therapy.


Quality of epilepsy care in a rural and deprived Scottish population.
Epilepsy is among the commonest neurological disorders globally. Appropriate prescription and good adherence to anticonvulsants can achieve seizure freedom rates of 70%. Scotland is an affluent nation with free at point-of-access health care but there remain significant healthcare inequalities, particularly associated with deprivation. Anecdotally, epileptics in rural Ayrshire rarely engage with healthcare services. We describe the prevalence and management of epilepsy in a deprived and rural Scottish population. Electronic records were used to obtain the following for patients with coded diagnoses of 'Epilepsy' or 'Seizures' within a general practice list of 3500 patients: demographics; diagnosis; seizure types; date and level (primary, secondary) of last review; last seizure date; anticonvulsant prescription; adherence; and any clinic discharge due to non-attendance. 92 patients were coded as above. 56 had a current diagnosis of epilepsy (prev 16.1/100,000). 69% had good adherence. 56% had good seizure control, with adherence associated with control. Of the 68% managed by primary care, 33% were uncontrolled and 13% had had an epilepsy review in the previous year. 45% of patients referred to secondary care were discharged for non-attendance. We demonstrate a high prevalence of epilepsy, low anticonvulsant adherence and sub-optimal rates of seizure freedom. These may be linked to poor attendance at specialist clinics. Management in primary care is challenging as evidenced by low review rates and high rates of ongoing seizures. We propose that the synergistic factors of uncontrolled epilepsy, deprivation and rurality make it difficult to attend clinics, with resultant health inequalities.


Expression and significance of HERG protein in gastric cancer.
Our previous studies showed that delayed rectifier potassium currents existed in human gastric cancer cells and the currents were related to the growth of gastric cancer cells. Human ether-a-go-go-related gene (herg) encoding alpha subunit of delayed rectifier potassium channel has been indicated with involvement in tumor cell growth and death. The purpose of the present study is to investigate the expression of HERG protein in gastric cancer tissue and cells; analyze the relationship between the expression of HERG protein and the clinicopathological characteristics of patients with gastric cancer; explore the effects of HERG protein on biological behaviours of gastric cancer cells. The expression of HERG protein in gastric cancer tissues and cells was measured by immunohistochemistry and Western blot, respectively. Reduction of HERG protein was carried out by siRNA technology. The proliferation, ability of clone formation, cell cycle, apoptosis and invasive ability of gastric cancer cells were evaluated by MTT assay, clone formation assay, flow cytometry and cell invasion assay. Tumor growth in nude mice was to be used to access the tumorigenicity of gastric cancer cells and HERG currents were recorded by patch-clamp. HERG protein was exclusively expressed in gastric cancer cells. The expression of HERG protein was associated with tumor differentiation, TNM stage and lymph node involvement of gastric cancer. Silencing HERG protein could eliminate the HERG currents and inhibit proliferation, clone formation, invasiveness and tumorigenicity of gastric cancer cells. Reducing HERG protein could also inhibit gastric cancer cells entering S phase from G(1) phase and induce apoptosis of gastric cancer cells. HERG protein is involved in carcinogenesis of gastric cancer and is a potential therapeutic target of gastric cancer.


Education in Female Sexual Function and Dysfunction among American Urogynecologic Society Members: An Unmet Need.
Sexual function is an important component of women's health that has not been traditionally emphasized during medical training, suggesting that further education is needed to provide comprehensive patient care. The purpose of this study was to describe education and interest in female sexual function among urogynecology providers. Conducted in 2020, this was a cross-sectional survey of American Urogynecologic Society members assessing educational and clinical experience with female sexual function. Of 642 members who opened the survey, 123 (19%) completed it. Most of the respondents were fellowship trained (70%), and 74% reported ≥10% of their patients had sexual function questions or concerns unrelated to prolapse or incontinence. Most (71%) of the members strongly agreed/agreed that they were comfortable evaluating and managing these patients. This was more common in providers who saw more patients (≥25%) with sexual function concerns (83%) compared with those who saw <25% (65%; P = 0.04). Most of the respondents reported receiving ≤1 lecture on normal sexual function (82%) or sexual dysfunction (85%) during medical training. Most (67%) would expand their practice if they received additional education. The most requested topics were disorders of desire (72%), orgasm (71%), and arousal (67%). The most common reasons for not expanding practice even with additional education were female sexual function not being of significant interest (30%) and time and interruption of practice flow (28%). Most of the respondents felt comfortable caring for patients with sexual function concerns, but reported that they would expand their practice with additional education. The majority reported having received ≤1 female sexual function/dysfunction lecture during their medical training. This highlights a critical need and desire for more female sexual function education among the urogynecologic provider population.


Relationship Between Ventricular Arrhythmias, Conduction Disorders, and Myocardial Fibrosis in Patients With Systemic Sclerosis.
Delayed-enhancement magnetic resonance imaging (DE-MRI) is a noninvasive diagnostic tool able to identify myocardial fibrosis. In patients with scleroderma, its relationship with arrhythmias and conduction disorders has not been fully explored. The aim of this study was to evaluate the possible correlations between ventricular arrhythmias, conduction disorders, and myocardial fibrosis in patients with systemic sclerosis. Thirty-six patients with diffuse or limited cutaneous scleroderma underwent 12-lead electrocardiogram (ECG), 24-hour Holter ECG monitoring, transthoracic echocardiography, and cardiac DE-MRI, with gadolinium administration in 33 patients. High-quality DE-MRI scans were obtained in 30 patients. Myocardial fibrosis was detected in 25 patients (83.3%). Eighteen patients (60%) had ventricular arrhythmias or conduction disorders. There was no significant difference in ventricular arrhythmia burden (the total number of premature ventricular contractions [PVCs]/24 hours) (48 ± 304 vs. 69 ± 236, P = 0.97), ventricular arrhythmia severity (couplets, triplets, runs) on Holter ECG, or in the presence of conduction disorders (36% vs. 40%, P = 0.86) between patients with and without myocardial fibrosis. In univariate analysis, diffuse fibrosis was weakly associated with the number of PVCs/24 hours (R = 0.157, P = 0.03). A number of at least 597 PVCs/24 hours had a sensitivity of 60% and a specificity of 92% in predicting the presence of diffuse fibrosis on DE-MRI (area under the curve = 0.640). Delayed-enhancement magnetic resonance imaging can identify myocardial fibrosis in a high percentage of scleroderma patients. Its presence does not seem to influence the ventricular arrhythmia burden and severity or the presence of conduction disorders, with the exception of diffuse myocardial fibrosis, which modestly influences the total number of PVCs/24 hours.


[Keratinocyte density of the cornea in vivo. Automated measurement with a modified confocal microscopy MICROPHTHAL].
The MICROPHTHAL is a confocal slit light scanning microscope for a non-invasive in-vivo examination of corneal structures of human eyes. With this instrument even thin layers of corneal tissue can be imaged in good quality. Otherwise, blurring of single frames and deviations from the z-axis in video-sequences caused by high speed movements of the eye would normally prevent a measurement the density of keratocytes in the cornea. The goal of the investigation was optical pachymetry, the automatical measurement of the keratocytes density and a 3D-dimensional reconstruction of the central cornea in-vivo under constant imaging conditions. We developed a low-vacuum suction cup system for stabilizing the eye in front of the microscope objective during the z-scan through the cornea. A stepmotor shifting system for the objective locates inside the suction cup with a central hole was installed underneath them icroscope. Control of this system via computer facilitated shifting the focal plane along the z-axis. The layer images were recorded using a S-VHS-tape and saved on the PC. The digital analysis was performed using a special software to automatically and off-line evaluate the density of keratocytes in combination with the 3D-reconstruction. The software also corrected the background illumination and small axial jitter. After this procedure the keratocytes density and the 3D-reconstruction in 70 images of the z-scan were calculated. We examined 47 corneas of 25 healthy probands. The range of age was 25-56 years. Independent control evaluation of the video sequences were taken manually on an INDIGO HIGH IMPACT workstation. By assign all keratocytes to the corneal measurement volume we found a averaged density of 15,730 cells/mm3 in the central cornea. The averaged thickness of the cornea was 0.556 mm. The control valuation of identical video-sequences on the workstation accomplished the same result of 16,000 keratocytes/mm3, also similar the result of the automatically measurement with the modified software. This modification of the microscope is a promising in-vivo tool for optical pachymetry and quantitative examination of corneal microstructures. The stabilization effect of the low-vacuum suction cup system in the front of the microscope for computer-controlled valuation of the density profile of keratocytes and the 3D-reconstruction of a central corneal volume element has produced encouraging results. Characterization of pathophysiological changes in the distribution of keratocytes after excimer laser ablation for phototherapeutic or photorefractive keratectomy, for example, can be estimated without pain for the patients.


Two new Cypridopsinae Kaufmann, 1900 (Crustacea, Ostracoda) from southern Africa.
Two new Cypridopsinae ostracods, Potamocyprismeissneri sp. nov. and Sarscypridopsisharundineti sp. nov. are described. Both were found only as asexual (all-female) populations in temporary waters of southern Africa. Potamocyprismeissneri was collected from a small pan in the North-West Province of South Africa. It is approximately 0.5 mm long and belongs to the species group with long swimming setae on the second antennae. However, the species has a somewhat isolated position in the genus owing to the conspicuously reticulated carapace, which is furthermore densely covered by prominent conuli with normal pores carrying long sensilla, as well as to the wide anterior and posterior flanges on the left valve. To allow identification of the new species in relation to its closest congeners, a key to the species of the genus Potamocypris Brady, 1870 from southern Africa is provided. The genus Sarscypridopsis McKenzie, 1977 mostly has an Afrotropical distribution with only few species occurring in other regions. Sarscypridopsisharundineti was collected from floodplains of the outskirts of the Okavango Delta in Botswana. It is approximately 0.4 mm long and can be distinguished from congeners mainly by the smaller and more oval-shaped valves. We conclude that southern African Cypridopsinae urgently need integrated taxonomic revision, by means of both morphological characters and DNA-sequence data.


The effectiveness of stress management training on blood glucose control in patients with type 2 diabetes.
Type 2 diabetes is a chronic disease that is expanding at an alarming rate in the world. Research on individuals with type 2 diabetes showed that stressful life events cause problems in the effective management and control of diabetes. This study aimed at investigating the effect of a stress management intervention on blood glucose control in individuals with type 2 diabetes referred to Zarandeh clinic, Iran. In this experimental study, 230 individuals with type 2 diabetes (179 female and 51 male) were enrolled and assigned to experimental (n = 115) and control (n = 115) groups. A valid and reliable multi-part questionnaire including demographics, Perceived Stress Scale, Coping Inventory for Stressful Situations, Coping Self-Efficacy Scale, and multidimensional scale of perceived social support was used to for data collection. The experimental group received a training program, developed based on the social cognitive theory and with an emphasis on improving self-efficacy and perceived social support, during eight sessions of one and a half hours. Control group received only standard care. Data were analyzed using SPSS 15 applying the t test, paired t-tests, Pearson correlation coefficient, and Chi square analysis. The significance level was considered at 0.05. Before the intervention, the mean perceived stress scores of the experimental and control groups were 33.9 ± 4.6 and 35 ± 6.5, respectively, and no significant difference was observed (p > 0.05). However, after the intervention, the mean perceived stress score of the experimental group (26.7 ± 4.7) was significantly less than that of the control group (34.5 ± 7) (p = 0.001). Before the intervention, the mean scores of HbA1c in the experimental and control groups were 8.52 ± 1 and 8.42 ± 1.2, respectively, and there was no significant difference between the two groups. However, after the intervention, the results showed a significant decrease in glycosylated hemoglobin levels in the experimental group (p ≤ 0.05). Moreover, after the intervention, the result showed a significant difference between the mean scores of all aspects of Coping Inventory for Stressful Situations, coping self-efficacy, and perceived social support in the two groups (p < 0.05). Our results suggested that the theory-based stress management intervention based on social cognitive theory may help to decrease stress and increase coping self-efficacy, stress management, perceived social support, and lead to a reduction in the glycosylated hemoglobin levels among patients with diabetes.


G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer?
Therapeutic outcome in head and neck squamous cell carcinoma (HNSCC) is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs) as promising candidates. Significant epigenetic silencing of GPCR expression occurs in HNSCC compared with normal tissue, and is significantly correlated with clinical behavior. Together with the finding that GPCR activity can suppress tumor cell growth, this indicates that GPCR expression has potential utility as a prognostic factor. In this review, we discuss the roles that galanin receptor type 1 (GALR1) and type 2 (GALR2), tachykinin receptor type 1 (TACR1), and somatostatin receptor type 1 (SST1) play in HNSCC. GALR1 inhibits proliferation of HNSCC cells though ERK1/2-mediated effects on cell cycle control proteins such as p27, p57, and cyclin D1, whereas GALR2 inhibits cell proliferation and induces apoptosis in HNSCC cells. Hypermethylation of GALR1, GALR2, TACR1, and SST1 is associated with significantly reduced disease-free survival and a higher recurrence rate. Although their overall activities varies, each of these GPCRs has value as both a prognostic factor and a therapeutic target. These data indicate that further study of GPCRs is a promising strategy that will enrich pharmacogenomics and prognostic research in HNSCC.


Increase in nitrosourea resistance in mammalian cells by retrovirally mediated gene transfer of bacterial O6-alkylguanine-DNA alkyltransferase.
Maloney murine leukemia virus-based, replication-defective retroviral vectors containing the neomycin resistance gene (neo) were developed to transfer the Escherichia coli ada gene coding for O6-alkylguanine-DNA alkyltransferase, into mammalian cells. To optimize gene transfer and expression, the following promoters were linked to ada: the Maloney murine leukemia virus promoter within the long-terminal repeat, the Rous sarcoma virus promoter, the thymidine kinase promoter, or the human phosphoglycerate kinase promoter. Sequences were transfected into the helper virus-free retroviral packaging psi-2 cell line. Recombinant retroviruses were tested in CCL-1 cells, which, like most murine tissues, have low levels of alkyltransferase and are sensitive to 1,3-bis(2-chloroethyl)nitrosourea (BCNU), and in NIH-3T3 cells, which are BCNU resistant and have high levels of alkyltransferase. Lines infected with each of the four retroviruses were selected for neo expression and found to have intact proviral integration and ada gene expression. Alkyltransferase activity was greatest with retrovirus containing the Rous sarcoma virus-ada gene; infected NIH-3T3 cells had up to 2300 units of alkyltransferase/mg of protein compared with 151 units/mg of protein in control cells, and infected CCL-1 cells had up to 1231 units/mg of protein compared with 33 units/mg of protein in control cells. CCL-1 cells expressing ada were more resistant to BCNU cytotoxicity than were controls. However, NIH-3T3 cells expressing ada were only slightly more resistant to BCNU than controls, possibly because most of the ada protein was cytoplasmic rather than nuclear as suggested by immunohistochemical stain. These studies establish a series of retroviruses containing the bacterial ada gene, which efficiently infect mammalian cells. ada expression increases nitrosourea resistance in cells with low mammalian alkyltransferase activity.


Gonorrhea treatment practices in the STD Surveillance Network, 2010-2012.
Replacing oral treatments with ceftriaxone is a central component of public health efforts to slow the emergence of cephalosporin-resistant Neisseria gonorrhoeae in the United States; US gonorrhea treatment guidelines were revised accordingly in 2010. However, current US gonorrhea treatment practices have not been well characterized. Six city and state health departments in Cycle II of the STD Surveillance Network (SSuN) contributed data on all gonorrhea cases reported in 101 counties and independent cities. Treatment data were obtained through local public health surveillance and interviews with a random sample of patients. Cases were weighted to adjust for site-specific sample fractions and for differential nonresponse by age, sex, and provider type. From 2010 to 2012, 135,984 gonorrhea cases were reported in participating areas, 15,246 (11.2%) of which were randomly sampled. Of these, 7,851 (51.5%) patients were interviewed. Among patients with complete treatment data, 76.8% received ceftriaxone, 16.4% received an oral cephalosporin, and 6.9% did not receive a cephalosporin; 51.9% of persons were treated with a regimen containing ceftriaxone and either doxycycline or azithromycin. Ceftriaxone treatment increased significantly by year (64.1% of patients in 2010, 79.3% in 2011, 85.4% in 2012; P = 0.0001). Ceftriaxone use varied widely by STD Surveillance Network site (from 44.6% to 95.1% in 2012). Most persons diagnosed as having gonorrhea between 2010 and 2012 in the United States received ceftriaxone, and its use has increased since the release of the 2010 Centers for Disease Control and Prevention STD Treatment Guidelines.


No outgrowth of chondrocytes from non-digested particulated articular cartilage embedded in commercially available fibrin matrix: an in vitro study.
Commercially available fibrin is routinely being used as both a matrix in certain cartilage repair techniques and a method for scaffold fixation. Chondrocytes from non-digested particulated cartilage fragments are proposed as a possible source for new cartilage tissue formation in some operative techniques. The goal of this study was to test that chondrocytes from particulated articular cartilage embedded in fibrin have an active role in the process of cartilage repair, as well as if commercially available fibrin should be used as a suitable matrix. Articular cartilage was obtained from patients undergoing total knee replacement surgery. The biopsies were particulated in small, 1-2-mm(3) pieces and embedded in fibrin. Two groups were compared in our study, particulated articular cartilage with and without collagenase treatment. The specimens were analyzed by optical microscopy after 2-5 weeks of cultivation in a special construct embedded in a cell culture medium containing particulated cartilage embedded in fibrin in the upper phase and cancellous bone in the lower phase under the perforated nylon membrane. None of the biopsies taken from four different patients showed the outgrowth of chondrocytes or bone marrow-originated cells into the fibrin matrix in our experimental model. It has been shown in our experimental model in vitro little to support the theory that articular chondrocytes from particulated articular cartilage embedded in fibrin have an active role in cartilage repair in its early stage.


Morphology of Puccinia horiana, Causal Agent of Chrysanthemum White Rust, Sampled From Naturally Infected Plants.
Chrysanthemum white rust (CWR), caused by Puccinia horiana, is pathogenic on many Chrysanthemum spp. and close relatives, and infects commercially important florist chrysanthemum cultivars (Chrysanthemum × morifolium) throughout the world. Due to regulations, most research and observations with CWR are done in vitro with symptomatic plants. In contrast, research presented herein is based on microscopic examination of symptomatic and asymptomatic plants collected from natural outbreaks in the field. We observed scattered (not in a linear pattern) telial sori on infected chrysanthemum leaves, stems, and flowers that coalesced at high infection levels. Teliospores were mainly two-celled but occasionally one- or three-celled. Promycelia arose from the apical teliospore cell, the basal cell, or both. The number of basidiospores on promycelia varied from one to four. Germ tubes, arising from P. horiana basidiospores, penetrated the host epidermis directly without appressoria. A mucilaginous exudate formed at the site of attachment and penetration of leaf and stem tissue, as well as on internal cell walls. P. horiana colonization was systemic, with intercellular mycelium and intracellular M-haustoria in both symptomatic and asymptomatic infected host tissue. Hyphal anastomosis was observed within infected plants, suggesting that asexual fusion between different P. horiana pathotypes or genotypes might occur.


The clinical pharmacist in drug research and development. Pharmacoepidemiology.
From the inception of drug monitoring research programs, pharmacists have played a key role in their design and implementation. As greater emphasis is placed on the value of these data bases, pharmacists will be increasingly called upon to conduct epidemiologic studies. Formalized training in the principles of epidemiology and biostatistics will allow pharmacists to expand their role in this important area of research.


[Spectrophotometric determination of amikacin and sisomicin in the air using the Hantzsch reaction].
A procedure for determination of amikacin and sisomicin in ambient air of production areas was developed. It is based on the Hantzsch reaction involving formation of dihydrolutidine derivatives on the antibiotic interaction with acetyl acetone and formaldehyde in acid media. The yellow-colored reaction products are subjected to spectrophotometry at 356 nm. The detection limits for amikacin and sisomicin are 0.005 and 0.01 mg respectively. The procedure may be used for routine sanitary inspection of ambient air for every of the above antibiotics in the absence of the other in production of the substances and their dosage forms.


Use of athymic nude mice for in vivo studies of human growth-hormone-secreting pituitary adenomas.
Human growth hormone (hGH)-secreting pituitary adenoma tissue of 31 acromegalic patients was transplanted subcutaneously onto 291 athymic nude mice. 37% of the transplanted adenoma fragments could be maintained vital up to 46 days. Histological examinations of the transplants revealed neither alterations in their morphological characteristics nor signs of growth. A maintenance or linear decline of hGH secretion of the transplants related to their vitality was observed by hGH radioimmunoassay. Estimation of graft vitality was improved by GH-releasing hormone (GHRH) stimulation in regular intervals. The rate of pituitary adenomas responding to GHRH was as high as in a major collective of acromegalic patients. Our method of positive selection of vital xenotransplanted hGH-secreting pituitary adenomas via hGH detection at regular intervals in combination with GHRH stimulation gives the opportunity of reliable in vivo research with these tumors.


Anti-HIV-1 activity of elafin is more potent than its precursor's, trappin-2, in genital epithelial cells.
Cervicovaginal lavage fluid (CVL) is a natural source of anti-HIV-1 factors; however, molecular characterization of the anti-HIV-1 activity of CVL remains elusive. In this study, we confirmed that CVLs from HIV-1-resistant (HIV-R) compared to HIV-1-susceptible (HIV-S) commercial sex workers (CSWs) contain significantly larger amounts of serine antiprotease trappin-2 (Tr) and its processed form, elafin (E). We assessed anti-HIV-1 activity of CVLs of CSWs and recombinant E and Tr on genital epithelial cells (ECs) that possess (TZM-bl) or lack (HEC-1A) canonical HIV-1 receptors. Our results showed that immunodepletion of 30% of Tr/E from CVL accounted for up to 60% of total anti-HIV-1 activity of CVL. Knockdown of endogenous Tr/E in HEC-1A cells resulted in significantly increased shedding of infectious R5 and X4 HIV-1. Pretreatment of R5, but not X4 HIV-1, with either Tr or E led to inhibition of HIV-1 infection of TZM-bl cells. Interestingly, when either HIV-1 or cells lacking canonical HIV-1 receptors were pretreated with Tr or E, HIV-1 attachment and transcytosis were significantly reduced, and decreased attachment was not associated with altered expression of syndecan-1 or CXCR4. Determination of 50% inhibitory concentrations (IC(50)) of Tr and E anti-HIV-1 activity indicated that E is ∼130 times more potent than its precursor, Tr, despite their equipotent antiprotease activities. This study provides the first experimental evidence that (i) Tr and E are among the principal anti-HIV-1 molecules of CVL; (ii) Tr and E affect cell attachment and transcytosis of HIV-1; (iii) E is more efficient than Tr regarding anti-HIV-1 activity; and (iv) the anti-HIV-1 effect of Tr and E is contextual.


The 3-Phase Process in the Cancer Experience of Adolescents and Young Adults.
When confronted with cancer, adolescents and young adults (AYAs) enter a psychosocial trajectory. Previous research has acknowledged the importance of care adjusted to the specific needs of AYAs. To develop AYA-focused care, in-depth knowledge about the experiences of AYAs with cancer is necessary. The purposes of this study were to discover the psychosocial experiences of and their meanings for AYAs enduring cancer, as well as its treatment and follow-up, and to capture the basic social psychological process that shaped these experiences. This was a qualitative study in which individual semistructured interviews were conducted with 23 participants aged 15 to 25 years. A 3-phase process was identified, which demonstrated alterations in the AYAs' experiences and their underlying meanings: (1) maintaining normal life was essential, (2) normal life was slipping away, and (3) evolving toward a new normal life after treatment. Certain core dynamics were present in these 3 phases. Throughout the cancer trajectory, the AYAs attempted to maintain control, redefine the self, and incorporate their cancer experience to the long-term course of life and had varying expectations of their social networks. Understanding the process that AYAs with cancer go through and taking into account their experiences can facilitate better psychosocial care for this emotionally vulnerable population. Healthcare professionals need to take a patient-centered approach, with a focus on communication, to meet the needs of AYAs throughout the cancer trajectory.


Nutrition and metabolism of the geriatric dog.
Sixteen 10-12-year-old and eight 1-year-old dogs were studied over a two year period to determine comparative differences in physiological response to 4 diets varying in protein content and percentages of energy contributed by protein. The ability of old dogs to utilize nutrients as supplied by these foods was not significantly different from that of young adult dogs. Except for indices of mitogenic stimulation and serum urea nitrogen (SUN) other physiological parameters studied were not affected by the diet fed. Regardless of diet, old dogs had significantly higher serum levels of cholesterol, phosphorus and alkaline phosphatase and had lower indices of mitogenic stimulation than did young dogs.


Axial super-resolution evanescent wave tomography.
Optical tomographic reconstruction of a three-dimensional (3D) nanoscale specimen is hindered by the axial diffraction limit, which is 2-3 times worse than the focal plane resolution. We propose and experimentally demonstrate an axial super-resolution evanescent wave tomography method that enables the use of regular evanescent wave microscopes like the total internal reflection fluorescence microscope beyond surface imaging and achieve a tomographic reconstruction with axial super-resolution. Our proposed method based on Fourier reconstruction achieves axial super-resolution by extracting information from multiple sets of 3D fluorescence images when the sample is illuminated by an evanescent wave. We propose a procedure to extract super-resolution features from the incremental penetration of an evanescent wave and support our theory by one-dimensional (along the optical axis) and 3D simulations. We validate our claims by experimentally demonstrating tomographic reconstruction of microtubules in HeLa cells with an axial resolution of ∼130 nm. Our method does not require any additional optical components or sample preparation. The proposed method can be combined with focal plane super-resolution techniques like stochastic optical reconstruction microscopy and can also be adapted for THz and microwave near-field tomography.


How myosin VI coordinates its heads during processive movement.
A processive molecular motor must coordinate the enzymatic state of its two catalytic domains in order to prevent premature detachment from its track. For myosin V, internal strain produced when both heads of are attached to an actin track prevents completion of the lever arm swing of the lead head and blocks ADP release. However, this mechanism cannot work for myosin VI, since its lever arm positions are reversed. Here, we demonstrate that myosin VI gating is achieved instead by blocking ATP binding to the lead head once it has released its ADP. The structural basis for this unique gating mechanism involves an insert near the nucleotide binding pocket that is found only in class VI myosin. Reverse strain greatly favors binding of ADP to the lead head, which makes it possible for myosin VI to function as a processive transporter as well as an actin-based anchor. While this mechanism is unlike that of any other myosin superfamily member, it bears remarkable similarities to that of another processive motor from a different superfamily--kinesin I.


[Research on siblings of mentally ill and retarded persons. Review of literature].
Author describes the developmental tasks of the siblingship from the family life cycle perspective. Next, research on physical and mental health eg. psychopathological symptoms of siblings of mentally ill and retarded persons as well as research on their difficulties, perception of the brother's or sister's illness and its significance for their development is presented. In the last part of the paper research conducted by D. Reiss from the University of G. Washington is discussed. The main goal is the assessment of the relationship of shared and nonshared environmental factors in the development of adolescents. Research on siblings is of special significance for the understanding of the relation between genetic and environmental factors in the development of the person, as well as for the theory of mental disorders, especially the role of the family.


Finger Temperature: A Psychophysiological Assessment of the Attentional State.
Attention is a key cognitive phenomenon that is studied to understand cognitive disorders or even to estimate workloads to prevent accidents. Usually, it is studied using brain activity, even though it has many psychophysiological correlates. In the present study, we aim to evaluate if finger temperature, as a surrogate of peripheral vasoconstriction, can be used to obtain similar and complementary information to electroencephalography (EEG) brain activity measurements. To conduct this, 34 participants were recruited and submitted to performing four tasks-one as a baseline, and three attentional tasks. These three attentional tasks measured sustained attention, resilience to distractors, and attentional resources. During the tasks, the room, forehead, tympanic, and finger temperatures were measured. Furthermore, we included a 32-channel EEG recording. Our results showed a strong monotonic association between the finger temperature and the Alpha and Beta EEG spectral bands. When predicting attentional performance, the finger temperature was complementary to the EEG spectral measurements, through the prediction of aspects of attentional performance that had not been assessed by spectral EEG activity, or through the improvement of the model's fit. We also found that during the baseline task (non-goal-oriented task), the spectral EEG activity has an inverted correlation, as compared to a goal-oriented task. Our current results suggest that the psychophysiological assessment of attention is complementary to classic EEG approach, while also having the advantage of easy implementation of analysis tools in environments of reducing control (workplaces, student classrooms).