Exploring the links between unhealthy eating behaviour and heavy alcohol use in the social, emotional and cultural lives of young adults (aged 18-25): A qualitative research study.
Alcohol use peaks in early adulthood and can contribute both directly and indirectly to unhealthy weight gain. This is the first qualitative study to explore the links between unhealthy eating behaviour and heavy alcohol use in the social, emotional and cultural lives of young adults. We conducted 45 in-depth interviews with 18-25-year-olds in North-East England to inform development of a dual-focused intervention to reduce health risk due to excess weight gain and alcohol use. Data were analysed thematically, following the principles of constant comparison, resulting in three intersecting themes: (1) how food and alcohol consumption currently link together for this population group; (2) influences upon linked eating and drinking behaviours and (3) young adults' feelings and concerns about linked eating and drinking behaviours. Socio-cultural, physical and emotional links between food and alcohol consumption were an unquestioned norm among young adults. Eating patterns linked to alcohol use were not tied only to hunger, but also to sociability, traditions and identity. Young adults conceptualised and calculated risks to weight, appearance and social status, rather than to long-term health. This study is the first to evidence the deeply interconnected nature of food and alcohol consumption for many young adults. Findings have important implications for intervention development, UK public health policy and practice, and point to a need for similar research in other countries.


Manifold regularized discriminative nonnegative matrix factorization with fast gradient descent.
Nonnegative matrix factorization (NMF) has become a popular data-representation method and has been widely used in image processing and pattern-recognition problems. This is because the learned bases can be interpreted as a natural parts-based representation of data and this interpretation is consistent with the psychological intuition of combining parts to form a whole. For practical classification tasks, however, NMF ignores both the local geometry of data and the discriminative information of different classes. In addition, existing research results show that the learned basis is unnecessarily parts-based because there is neither explicit nor implicit constraint to ensure the representation parts-based. In this paper, we introduce the manifold regularization and the margin maximization to NMF and obtain the manifold regularized discriminative NMF (MD-NMF) to overcome the aforementioned problems. The multiplicative update rule (MUR) can be applied to optimizing MD-NMF, but it converges slowly. In this paper, we propose a fast gradient descent (FGD) to optimize MD-NMF. FGD contains a Newton method that searches the optimal step length, and thus, FGD converges much faster than MUR. In addition, FGD includes MUR as a special case and can be applied to optimizing NMF and its variants. For a problem with 165 samples in R(1600), FGD converges in 28 s, while MUR requires 282 s. We also apply FGD in a variant of MD-NMF and experimental results confirm its efficiency. Experimental results on several face image datasets suggest the effectiveness of MD-NMF.


Polymyxin P is the active principle in suppressing phytopathogenic Erwinia spp. by the biocontrol rhizobacterium Paenibacillus polymyxa M-1.
Nine gene clusters dedicated to nonribosomal synthesis of secondary metabolites with possible antimicrobial action, including polymyxin and fusaricidin, were detected within the whole genome sequence of the plant growth-promoting rhizobacterium (PGPR) Paenibacillus polymyxa M-1. To survey the antimicrobial compounds expressed by M-1 we analyzed the active principle suppressing phytopathogenic Erwinia spp. P. polymyxa M-1 suppressed the growth of phytopathogenic Erwinia amylovora Ea 273, and E. carotovora, the causative agents of fire blight and soft rot, respectively. By MALDI-TOF mass spectrometry and reversed-phase high-performance liquid chromatography (RP-HPLC), two antibacterial compounds bearing molecular masses of 1190.9 Da and 1176.9 Da were detected as being the two components of polymyxin P, polymyxin P1 and P2, respectively. The active principle acting against the two Erwinia strains was isolated from TLC plates and identified by postsource decay (PSD)-MALDI-TOF mass spectrometry as polymyxin P1 and polymyxin P2. These findings were corroborated by domain structure analysis of the polymyxin (pmx) gene cluster detected in the M-1 chromosome which revealed that corresponding to the chemical structure of polymyxin P, the gene cluster is encoding D-Phe in position 6 and L-Thr in position 7. Identical morphological changes in the cell wall of the bacterial phytopathogens treated with either crude polymyxin P or culture supernatant of M-1 corroborated that polymyxin P is the main component of the biocontrol effect exerted by strain M-1 against phytopathogenic Erwinia spp.


Effects of provider characteristics on care coordination under comanagement.
Care coordination is critical in settings characterized by high levels of uncertainty, time constraints, and interdependent work processes. The effects of provider characteristics on coordination in comanaged teams has never been examined. To characterize individual providers based on their contribution to team coordination. Hospitalists, nonphysician providers, hepatologists, and fellows on a comanaged liver service of an academic hospital. Between April 2008 and October 2008, participants were surveyed at baseline and repeatedly at the completion of physician rotations to assess their preferred and actual comanagement structures. In addition, they repeatedly rated their comanagers' contributions to overall coordination using an instrument that assessed relational coordination (RC). Providers were categorized into tertiles of RC. Their management preferences and the frequency of a "composite bad outcome" (intensive care unit [ICU] transfer or inpatient death) in each tertile were evaluated. All (100%) Baseline Surveys and 177/224 (79%) Repeated Surveys were completed by 32 providers. RC was shown to be a stable attribute of providers and not of adverse patient outcomes. Higher coordinators were characterized by their "ownership of patients" (higher 86% vs. lowest 20%, P < 0.01). High compared to low coordinator hepatologists demonstrated leadership through a broader delegation of tasks as well as self-assignment of responsibilities. A trend toward more frequent "composite bad outcomes" was seen for low tertile physicians: hospitalists (low 8.6% vs. high 1.1%, P < 0.01), hepatologists (low 5.2% vs. high 2.0%, P = 0.22), fellows (low 5.8% vs. high 1.8%, P = 0.08). Individual provider's teamwork-related disposition affects perceived coordination on comanaged team and may influence patient outcomes.


High-resolution angioscopic imaging during endovascular neurosurgery.
Endoluminal optical imaging, or angioscopy, has not seen widespread application during neurointerventional procedures, largely as a result of the poor imaging resolution of existing angioscopes. Scanning fiber endoscopes (SFEs) are a novel endoscopic platform that allows high-resolution video imaging in an ultraminiature form factor that is compatible with currently used distal access endoluminal catheters. To test the feasibility and potential utility of high-resolution angioscopy with an SFE during common endovascular neurosurgical procedures. A 3.7-French SFE was used in a porcine model system to image endothelial disruption, ischemic stroke and mechanical thrombectomy, aneurysm coiling, and flow-diverting stent placement. High-resolution, video-rate imaging was shown to be possible during all of the common procedures tested and provided information that was complementary to standard fluoroscopic imaging. SFE angioscopy was able to assess novel factors such as aneurysm base coverage fraction and side branch patency, which have previously not been possible to determine with conventional angiography. Endovascular imaging with an SFE provides important information on factors that cannot be assessed fluoroscopically and is a novel platform on which future neurointerventional techniques may be based because it allows for periprocedural inspection of the integrity of the vascular system and the deployed devices. In addition, it may be of diagnostic use for inspecting the vascular wall and postprocedure device evaluation.


Association between Depression, Antidepression Medications, and the Risk of Developing Type 2 Diabetes Mellitus: A Nationwide Population-Based Retrospective Cohort Study in Taiwan.
The relationship between depression, antidepressant medications (ADMs), and the risk of subsequent type 2 diabetes mellitus (T2DM) development remains controversial. Thus, we investigated this aspect by a population-based retrospective cohort study using the Longitudinal Health Insurance Database 2000 available in Taiwan. This large, observational study included 46,201 patients with depression and a 1 : 1 age- and sex-matched nondepression cohort enrolled between January 1, 2000, and December 31, 2013, and the newly diagnosed T2DM incidence rates were determined. We estimated the effects of depression on T2DM and the cumulative incidence curves by Cox proportional regression hazard models and Kaplan-Meier methods, respectively. We found that 47.97% of the patients with depression did not receive ADM. Among patients with depression who received ADM, 29.71%, 6.29%, 0.05%, 9.65%, and 6.32% received selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), heterocyclic antidepressants, and other medications, respectively. Patients without ADM treatment had a 39% higher risk of developing T2DM. However, those who received ADM treatment had a significantly lower risk of T2DM development in every treatment category. Depressive disorder treated with ADMs, especially with long-term use, was associated with an 11-48% decrease in the risk of T2DM in all ADM groups; however, heterocyclic antidepressant treatment for shorter periods (<80 days) was not significantly associated with a decreased risk of T2DM. The incidence of T2DM in Taiwan was found to be associated with an a priori history of depression and was inversely correlated with ADM treatment.


Blastomycosis in nondomestic felids.
Blastomycosis was diagnosed in six nondomestic felids from eastern Tennessee, including two Asian lions (Panthera leo persicus), one African lion (Panthera leo), one Siberian tiger (Panthera tigris), one cheetah (Acinonyx jubatus), and one snow leopard (Panthera uncia). Clinical signs included lethargy, anorexia, weight loss, dyspnea, sneezing. ataxia, and paresis. Variable nonspecific changes included leukocytosis, monocytosis, moderate left shift of neutrophils, moderate hypercalcemia, hyperproteinemia, and hyperglobulinemia. Thoracic radiographs revealed interstitial and alveolar changes, consolidation or collapse of a lung lobe, bullae formation, and a pulmonary mass. Agar gel immunodiffusion (AGID) serology for Blastomyces dermatitidis was performed in five felids and was positive in three. The tiger had cerebral blastomycosis and was positive for AGID serologic tests of both cerebrospinal fluid and serum. One percutaneous lung aspirate in the snow leopard and one bronchial aspirate in an Asian lion demonstrated B. dermatitidis organisms. whereas tracheal wash samples and a nasal discharge were nondiagnostic in others. Treatment with itraconazole was attempted in four cats. The tiger improved before euthanasia, whereas the others did not survive beyond initial treatments. In four felids, B. dermatitidis was found in the lungs and tracheobronchial lymph nodes associated with a florid pyogranulomatous reaction; the tiger had a pyogranulomatous encephalomyelitis, and the cheetah had a single pulmonary granuloma. Thoracic radiography, cytologic examination of lung lesion aspirates, and B. dermatitidis AGID serology should be performed on clinically ill zoo felids in endemic areas to rule out blastomycosis.


Optimal Dosing of Levetiracetam for Seizure Prophylaxis in Critically Ill Patients: A Prospective Observational Study.
Critically ill patients eliminate levetiracetam (LEV) more rapidly than healthy controls, yet low doses are commonly used for seizure prophylaxis in the ICU setting. We compared the rates of achievement of target serum levels and new onset seizure (clinical and/or electrographic) among patients who received low (500 mg bid) versus high (750-1,000 mg bid) dose LEV. Prospective, observational study. Tertiary care, academic center. We included patients who received prophylactic LEV following traumatic brain injury, intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, or supratentorial neurosurgery between 2019 and 2021. Patients with a history of seizure, antiseizure medication use, or renal failure requiring dialysis were excluded. None. LEV levels were obtained at steady state. The impact of low-dose versus high-dose LEV on the primary outcome of target LEV levels (12-46 μg/mL), and the secondary outcome of clinical and/or electrographic seizure, were assessed using multivariable logistic regression analyses adjusting for age, LEV loading dose, BMI, primary diagnosis and creatinine clearance (CrCl). Of the 205 subjects included in analyses, n = 106 (52%) received LEV 500 mg bid (median 13 mg/kg/d), and n = 99 (48%) received LEV 750-1,000 mg bid (median 25 mg/kg/d). Overall, 111 of 205 patients (54%) achieved target levels: 48 (45%) from the low-dose group versus 63 (64%) from the high-dose group (odds ratio [OR] 2.1; 95% CI, 1.1-3.7; p = 0.009). In multivariable analyses, high-dose LEV predicted target levels (adjusted OR [aOR] 2.23; 95% CI, 1.16-4.27; p = 0.016), and was associated with lower seizure odds (aOR 0.32; 95% CI, 0.13-0.82; p = 0.018) after adjusting for age, loading dose, BMI, diagnosis, and CrCl. Underdosing of LEV was common, with only 54% of patients achieving target serum levels. Higher doses (750-1,000 mg bid) were more than twice as likely to lead to optimal drug levels and reduced the odds of seizure by 68% compared with low-dose regimens (500 mg bid).


An Examination of Rostral Anterior Cingulate Cortex Function and Neurochemistry in Obsessive-Compulsive Disorder.
The anterior cingulate cortex is implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, few studies have examined functional and neurochemical abnormalities specifically in the rostral subdivision of the ACC (rACC) in OCD patients. We used functional magnetic resonance imaging (fMRI) during an emotional counting Stroop task and single-voxel J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) in the rACC to examine the function and neurochemistry of the rACC in individuals with OCD and comparison individuals without OCD. Between-group differences in rACC activation and glutamine/glutamate ratio (Gln/Glu), Glu, and Gln levels, as well as associations between rACC activation, Gln/Glu, Glu, Gln, behavioral, and clinical measures were examined using linear regression. In a sample of 30 participants with OCD and 29 age- and sex-matched participants without OCD, participants with OCD displayed significantly reduced rACC deactivation compared with those without OCD in response to OCD-specific words versus neutral words on the emotional counting Stroop task. However, Gln/Glu, Glu, and Gln in the rACC did not differ between groups nor was there an association between reduced rACC deactivation and Gln/Glu, Glu, or Gln in the OCD group. Taken together, these findings strengthen the evidence for rACC dysfunction in OCD, but weigh against an underlying association with abnormal rACC glutamatergic neurotransmission.


Altered neutrophil maturation patterns that limit identification of myelodysplastic syndromes.
Altered neutrophil maturation patterns have been reported useful for identification of myelodysplastic syndromes (MDS). Neutrophil maturation patterns based on CD11b, CD13, and CD16 were visually and numerically evaluated in 19 control, 23 MDS, 37 nondiagnostic for MDS (NDM) specimens, and 19 also processed 1 and 2 days subsequently. In contrast to maturation patterns illustrated previously by others as "normal," 84% of controls displayed diminished acquisition of CD16, imparting a contracted appearance. Such divergence from published "normal" patterns was usually mild-moderate, considered nonspecific, and associated with delayed processing: longer intervals between collection and processing (median 20.5 vs. 5.2 h), and following 1 and 2 days delay. Findings restricted to nonspecific contraction were found in 56% MDS and 78% NDM specimens. Evaluation for aberrant patterns was still performed with mild-moderate contraction present, but concern for over interpretation led to use of an equivocal-aberrant category. Nine cases had aberrant or equivocal-aberrant patterns (seven MDS, two NDM) with distinct visual alterations that differed from nonspecific contraction and had numerical evidence for a left shift: myeloblasts increased (67%) and least mature neutrophils (CD11b-/low, CD16-/low) increased (78%). Although evidence for a left shift was associated with MDS, it was also seen in NDM specimens with a synchronous left shift. Neutrophil maturation patterns that diverge from previously illustrated "normal" patterns, not specific for MDS, may be common in some settings. Laboratories seeking to implement FC evaluation for MDS must determine which findings have sufficient specificity for MDS within their own practice and patient population.


Epidemiology and risk factors for idiosyncratic drug-induced liver injury.
Idiosyncratic drug-induced liver injury (DILI) is, like other adverse effects of drugs, underreported and underestimated in most epidemiological studies based on registries of DILI cases and reporting systems (e.g., Medwatch). The same is probably true for prospective population-based studies, although they are much more likely to mirror the true incidence of DILI. Despite these challenges, the epidemiology of DILI remains of utmost importance and is gradually coming into better focus. A recent population based study found a crude incidence of ∼19 cases per 100,000 per year. Certain agents are particularly noteworthy for their DILI risk. Amoxicillin-clavulanate continues to be the most commonly implicated agent occurring in ∼1 out of 2,300 users. Some others that standout with significantly higher risk include azathioprine and infliximab. Although statin-induced hepatotoxicity has been well documented, the risk is probably quite low. Overall, the majority of DILI in children and adults is associated with either antibiotics or anticonvulsants. Drug-induced liver injury associated with intravenously given drugs does not show any major differences from DILI due to orally administered agents. Unfortunately, our understanding of pretherapy risk assessment remains rudimentary for the most part.


The Use of Pentaploid Crosses for the Introgression of Amblyopyrum muticum and D-Genome Chromosome Segments Into Durum Wheat.
The wild relatives of wheat provide an important source of genetic variation for wheat improvement. Much of the work in the past aimed at transferring genetic variation from wild relatives into wheat has relied on the exploitation of the ph1b mutant, located on the long arm of chromosome 5B. This mutation allows homologous recombination to occur between chromosomes from related but different genomes, e.g. between the chromosomes of wheat and related chromosomes from a wild relative resulting in the generation of interspecific recombinant chromosomes. However, the ph1b mutant also enables recombination to occur between the homologous genomes of wheat, e.g. A/B, A/D, B/D, resulting in the generation of wheat intergenomic recombinant chromosomes. In this work we report on the presence of wheat intergenomic recombinants in the genomic background of hexaploid wheat/Amblyopyrum muticum introgression lines. The transfer of genomic rearrangements involving the D-genome through pentaploid crosses provides a strategy by which the D-genome of wheat can be introgressed into durum wheat. Hence, a pentaploid crossing strategy was used to transfer D-genome segments, introgressed with either the A- and/or the B-genome, into the tetraploid background of two durum wheat genotypes Karim and Om Rabi 5 in either the presence or absence of different Am. muticum (2n = 2x = 14, TT) introgressions. Introgressions were monitored in backcross generations to the durum wheat parents via multi-color genomic in situ hybridization (mc-GISH). Tetraploid lines carrying homozygous D-genome introgressions, as well as simultaneous homozygous D- and T-genome introgressions, were developed. Introgression lines were characterized via Kompetitive Allele-Specific PCR (KASP) markers and multi-color fluorescence in situ hybridization (FISH). Results showed that new wheat sub-genomic translocations were generated at each generation in progeny that carried any Am. muticum chromosome introgression irrespective of the linkage group that the segment was derived from. The highest frequencies of homologous recombination were observed between the A- and the D-genomes. Results indicated that the genotype Karim had a higher tolerance to genomic rearrangements and T-genome introgressions compared to Om Rabi 5. This indicates the importance of the selection of the parental genotype when attempting to transfer/develop introgressions into durum wheat from pentaploid crosses.


Relationship between CO2 Assimilation, Photosynthetic Electron Transport, and Active O2 Metabolism in Leaves of Maize in the Field during Periods of Low Temperature
Measurements of the quantum efficiencies of photosynthetic electron transport through photosystem II (phiPSII) and CO2 assimilation (phiCO2) were made simultaneously on leaves of maize (Zea mays) crops in the United Kingdom during the early growing season, when chilling conditions were experienced. The activities of a range of enzymes involved with scavenging active O2 species and the levels of key antioxidants were also measured. When leaves were exposed to low temperatures during development, the ratio of phiPSII/phiCO2 was elevated, indicating the operation of an alternative sink to CO2 for photosynthetic reducing equivalents. The activities of ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, glutathione reductase, and superoxide dismutase and the levels of ascorbate and alpha-tocopherol were also elevated during chilling periods. This supports the hypothesis that the relative flux of photosynthetic reducing equivalents to O2 via the Mehler reaction is higher when leaves develop under chilling conditions. Lipoxygenase activity and lipid peroxidation were also increased during low temperatures, suggesting that lipoxygenase-mediated peroxidation of membrane lipids contributes to the oxidative damage occurring in chill-stressed leaves.


Assessment of rapid tests for detection of human immunodeficiency virus-specific antibodies in recently infected individuals.
We have evaluated four current Food and Drug Administration-cleared rapid tests for human immunodeficiency virus (HIV)-specific antibodies with a panel of specimens from recently infected individuals. Recent infection was detected by RNA-based screening coupled with enzyme immunoassay-based testing. We found that the sensitivities of the various rapid tests vary greatly with regard to their ability to detect HIV-specific antibodies in recently infected individuals.


Molecular interactions of antibodies with PD-1/PD-L1 proteins.
Aim: To compare the protein-protein interactions of antibodies targeting PD-1 and its ligand (PD-L1) with their targets in an attempt to explain the antibodies' binding affinity. Materials & methods: The structural features of complexes between pembrolizumab, nivolumab, durvalumab, atezolizumab, avelumab and PD-1/PD-L1 are described, with the use of software and based on crystallographic data. Results: Pembrolizumab has more structural features, including the number and type of the bonds and total binding surface area, which could rationalize its different clinical behavior compared with nivolumab. Similarly, protein-protein interactions with PD-L1 differ among durvalumab, atezolizumab and avelumab. Conclusion: Differential protein-protein interactions between antibodies and PD-1/PD-L1 may indicate differential clinical activity; however, further research is needed to provide evidence.


Melkersson-Rosenthal syndrome. A review of the literature and case report.
Melkersson-Rosenthal syndrome is an uncommon condition of obscure aetiology and uncertain pathogenesis. It is characterized by swelling of the lips or other parts of the face and mouth, Bell's palsy, and fissured tongue. Disturbances of salivary, lacrimal and nasal secretion, disorders of taste and vision, migraine, and febrile symptoms occasionally accompany the condition. Treatment is aimed at management of the facial paralysis and cosmetic reduction of established facial swelling.


[Expression and characterization of soluble recombinant Ulp1p with glutathione S-transferase tag in Escherichia coli].
The aim of the study is to obtain an efficient expression of recombinant ubiquitin-like specific protease 1 (Ulp1) by gene engineering. We cloned the Ulp1p, active fragment (403 aa-621 aa) of Ulp1, from Saccharomyces cerevisia, and subcloned into pGEX/Rosetta (DE3) to form an expression plasmid, pGEX-Ulp1p-His6. In order to enhance the solubility of GST-Ulp1p-His6, we purified the fusion protein GST-Ulp1p-His6 by either glutathione S-transferase agarose or Ni-NTA resin chromatography, the purity was up to 98%. We utilized the protein to cleave the SUMO fusions, and the specific activity of GST-Ulp1p-His6 was 1.375 x 10(4) U/mg. This study showed that the recombinant protein GST-Ulp1p-His6 displayed high specificity and activity.


[Railway use of asbestos-containing rubble: environmental hygienic aspects].
The paper presents the results of a study of the gravimetric and counting concentrations of respirable asbestos fibers while working with sand-and-crushed stone mixtures, obtained from the concentration of chrysotile asbestos, at distances of 25, 50, and 100 m from the working place, as well as in a car saloon when the electric train passes along the area of these operations following an hour, a day, and a year after the completion of work, in warm and colds seasons of a year. It is concluded that the use of asbestos-containing sand-and-crushed stone mixtures on the railway leads to a higher anthropogenic asbestos load on the population living in the railway right-of-way, on railway workers and passengers. In this connection, it is necessary to evaluate risk factors of asbestos-induced diseases among the above contingents. The authors consider that due to the fact that asbestos-containing sand-and-crushed stone mixtures are well wetted with water, followed by the formation of a firm surface crust that prevents dust formation, as well as the short duration and rare frequency of operations relating their change, it is necessary to irrigate the repair areas with water or surfactant liquids after work termination.


Identification and characterization of an archaeon-specific riboflavin kinase.
The riboflavin kinase in Methanocaldococcus jannaschii has been identified as the product of the MJ0056 gene. Recombinant expression of the MJ0056 gene in Escherichia coli led to a large increase in the amount of flavin mononucleotide (FMN) in the E. coli cell extract. The unexpected features of the purified recombinant enzyme were its use of CTP as the phosphoryl donor and the absence of a requirement for added metal ion to catalyze the formation of FMN. Identification of this riboflavin kinase fills another gap in the archaeal flavin biosynthetic pathway. Some divalent metals were found to be potent inhibitors of the reaction. The enzyme represents a unique CTP-dependent family of kinases.


Subjective and Real Time: Coding Under Different Drug States.
Organisms are constantly extracting information from the temporal structure of the environment, which allows them to select appropriate actions and predict impending changes. Several lines of research have suggested that interval timing is modulated by the dopaminergic system. It has been proposed that higher levels of dopamine cause an internal clock to speed up, whereas less dopamine causes a deceleration of the clock. In most experiments the subjects are first trained to perform a timing task while drug free. Consequently, most of what is known about the influence of dopaminergic modulation of timing is on well-established timing performance. In the current study the impact of altered DA on the acquisition of temporal control was the focal question. Thirty male Sprague-Dawley rats were distributed randomly into three different groups (haloperidol, d-amphetamine or vehicle). Each animal received an injection 15 min prior to the start of every session from the beginning of interval training. The subjects were trained in a Fixed Interval (FI) 16s schedule followed by training on a peak procedure in which 64s non-reinforced peak trials were intermixed with FI trials. In a final test session all subjects were given vehicle injections and 10 consecutive non-reinforced peak trials to see if training under drug conditions altered the encoding of time. The current study suggests that administration of drugs that modulate dopamine do not alter the encoding temporal durations but do acutely affect the initiation of responding.


Mucosal proctectomy and ileoanal pull-through technique and functional results in 23 consecutive patients.
Mucosal proctectomy with ileoanal pull-through in the treatment of ulcerative colitis and familial polyposis provides a technique for the preservation of the anal sphincters and relatively normal mechanisms of continence. Five patients had straight ileoanal anastomosis while 18 had the construction of a J-pouch. A two-team approach was used for simultaneous abdominal and perineal procedures to facilitate a shortened operating time. A loop ileostomy was routinely used in the postoperative period and was closed an average of 4.5 months (range: 2-16 months) later without complication. Prolonged preoperative hospitalization was rarely necessary and outpatient steroid enema preparation was routinely used. There were no deaths. Nineteen patients with functioning pull-through procedures have been followed an average of 23 months (range: 3-42 months). Two other patients have not had ileostomy closure because of complications. The two remaining patients had intractable diarrhea and have since undergone conversion to a permanent ileostomy. The 19 patients are continent, having three to nine bowel movements each day. Nearly all wear a perineal sanitary pad because of rare, unpredictable leakage of small amounts of fluid, especially at night. Complications were significant in this group of patients. Intestinal obstruction was a frequent problem, occurring in 52 per cent of the entire series and necessitating reoperation in 22 per cent. Anal stricture was a problem in another five patients. A variety of other minor problems occurred and most were treated nonoperatively. In spite of moderate diarrhea and occasional leakage of stool, all patients with functioning pull-through procedures prefer their current status to life with an ileostomy.(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanisms underlying palmitic acid-induced disruption of locomotor activity and sleep behavior in Drosophila.
The globally prevalent of sleep disorders is partly attributed to unhealthy dietary habits. This study investigated the underlying mechanisms of elevated palmitic acid (PA) intake on locomotor activity and sleep behavior in Drosophila. Our results indicate that exposure to PA significantly elevated Drosophila's daytime and nighttime locomotor activity while concurrently reducing overall sleep duration. Utilizing 16S rRNA sequencing, we observed substantial alterations in the composition of the gut microbiota induced by PA, notably, characterized by a significant reduction in Lactobacillus plantarum. Furthermore, PA significantly increased the levels of inflammatory factors Upd3 and Eiger in Drosophila intestines, and downregulated the expression of Gad and Tph, as well as 5-HT1A. Conversely, Gdh and Hdc were significantly upregulated in the PA group. Supplementation with L. plantarum or lactic acid significantly ameliorated PA-induced disruptions in both locomotor activity and sleep behavior. This supplementation also suppressed the expression of intestinal inflammatory factors, thus restoring impaired neurotransmitter-mediated sleep-wake regulation. Moreover, specific knockdown of intestinal epithelial Upd3 or Eiger similarly restored disrupted neurotransmitter expression, ultimately improving PA-induced disturbances in Drosophila locomotor activity and sleep behavior. These findings provide important insights into the intricate interplay between dietary components and essential behaviors, highlighting potential avenues for addressing health challenges associated with modern dietary habits.


Movement Velocity and Fluidity Improve after Armeo®Spring Rehabilitation in Children Affected by Acquired and Congenital Brain Diseases: An Observational Study.
Children with cerebral palsy (CP) and acquired brain injury (ABI) often exhibit upper limb impairment, with repercussions in their daily activities. Robotic rehabilitation may promote their functional recovery, but evidence of its effectiveness is often based on qualitative functional scales. The primary aim of the present work was to assess movement precision, velocity, and smoothness using numerical indices from the endpoint trajectory of Armeo®Spring. Secondly, an investigation of the effectiveness of robotic rehabilitation in CP and ABI children was performed. Upper limb functional changes were evaluated in children with CP (N=21) or ABI (N=22) treated with Armeo®Spring (20 45-minute sessions over 4 weeks) using clinical scales and numerical indices computed from the exoskeleton trajectory. Functional scales (i.e., QUEST and Melbourne) were sensitive to changes produced by the treatment for the whole study group and for the two etiology-based subgroups (improvements above Minimal Clinically Importance Difference). Significant improvement was also observed in terms of velocity, fluidity, and precision of the movement through the numerical indices of kinematic performance. Differences in the temporal evolution of the motor outcome were highlighted between the ABI and CP subgroups, pointing toward adopting different rehabilitative protocols in these two populations. Robot-assisted upper limb rehabilitation seems to be a promising tool to promote and assess rehabilitation in children affected by acquired and congenital brain diseases.


Cellulose-based Nanocarriers as Platforms for Cancer Therapy.
Cellulose is an important environmentally-friendly renewable polymer on the earth. Cellulose has been widely used as feedstocks for the synthesis of biomaterials, biofuels and biochemicals. Recently, cellulose and cellulose derivatives have received intense attention in biomedical applications, such as tissue engineering, scaffold, artificial blood vessel, skin grafts, artificial skin, drug carrier, and chronic skin diseases, many of which are somehow related to cancer therapy. In this mini-review, we focus on the up-to-date development of cellulosebased nanocarriers used for cancer therapy. Various cellulose-based nanocarriers such as bacterial cellulose (BC), cellulose acetate, microcrystalline cellulose, carboxymethyl cellulose, cellulose nanocrystals, cellulose nanofibrills, etc, are reviewed in terms of being used in drug delivery systems for cancer treatment. Different strategies for the synthesis of cellulose-based nanocarriers are summarized. Special attention is paid on the structure and properties of cellulose-based drug carriers for cancer therapy via some representative examples. Finally, the problems and future developments of these promising polymeric nanocarriers are raised and proposed.


Dynamics underlying rhythmic and non-rhythmic variants of abnormal, waking delta activity.
We applied a new test, nonlinear cross prediction (NLCP), to investigate whether or polymorphic delta activity (PDA) and frontal intermittent rhythmic delta activity (FIRDA) reflect linear or nonlinear brain dynamics. Furthermore realistic models were constructed to explain the dynamical properties of PDA and FIRDA. Forty-nine EEG time series with FIRDA and 40 time series with PDA were studied with the NLCP algorithm. This characterizes a time series in terms of its predictability, amplitude asymmetry, and time asymmetry, with the latter two measures reflecting nonlinearity. Parameters of an EEG model proposed by Lopes da Silva were adjusted to obtain time series resembling PDA and FIRDA. FIRDA was more predictable than PDA. Most PDA segments could not be distinguished from linearly filtered noise. In contrast, FIRDA activity showed strong evidence of nonlinear dynamics. These dynamical properties of PDA and FIRDA could be reproduced by the Lopes da Silva model. PDA and FIRDA reflect a point attractor and a limit cycle attractor, respectively, perturbed by dynamical noise. Experimental analysis and modeling of the data suggest that PDA and FIRDA reflect fundamentally different types of brain dynamics. While PDA is filtered noise, reflecting low-level, random input to cortical networks, FIRDA may reflect limit-cycle oscillations due to increased excitation.


Confirmation study of prostate cancer risk variants at 8q24 in African Americans identifies a novel risk locus.
Prostate cancer is a common complex disease that disproportionately affects men of African descent. Recently, several different common variants on chromosome 8q24 have been shown to be associated with prostate cancer in multiple studies and ethnic groups. The objective of this study was to confirm the association of 8q24 markers with prostate cancer in African Americans. We genotyped 24 markers along 8q24 and 80 unlinked ancestry informative markers in a hospital-based case-control sample of 1057 African American men (490 prostate cancer cases and 567 controls). Association analyses of 8q24 markers with prostate cancer risk were adjusted for both global and local 8q24 admixture stratification using estimates from ancestry informative markers. We report that rs7008482, which maps to the 8q24.13 region, is an additional independent prostate cancer risk variant (P = 5 x 10(-4)), and we also replicate the association of rs16901979 with prostate cancer (P = 0.002). Other published risk variants in the region such as rs1447295 and rs6983267 showed a similar direction and magnitude of effect, but were not significant in our population. Both rs7008482 and rs16901979 independently predicted risk and remained significant (P < 0.001) after controlling for each other. Our data combined with additional replications of 8q24 markers provide compelling support for multiple regions of risk for prostate cancer on 8q24.


The Community Balance and Mobility Scale: A VALID ASSESSMENT TOOL OF BALANCE IN CARDIAC REHABILITATION PATIENTS.
Many patients participating in cardiac rehabilitation (CR) programs have decreased balance. This is a concern, as it may affect their ability to optimally perform physical exercise in CR and thus decrease CR efficacy. Despite this concern, balance is typically not assessed as part of CR intake. This may be attributable to the fact that a suitable balance assessment tool has not been identified for higher-functioning CR patients. A potential solution to this issue is using the Community Balance and Mobility Scale (CBMS), which has been used to assess balance in higher-functioning clinical populations; however, its use in a CR population has never been investigated. Therefore, the purpose of this study was to determine the reliability and validity of the CBMS for assessing balance in CR patients. Fifty-three participants were recruited from local CR programs to perform the CBMS. Dynamic posturography was also measured in a subset of participants (n = 31) using the Limits of Stability (LOS) test. Analysis of CBMS scores revealed that the mean CBMS score was 61.9 ± 16.2 (out of 96) and that no floor or ceiling effects were observed for any participants. CBMS scores were significantly correlated with the LOS results (0.41-0.53). Interrater reliability between novice and expert testers was strong (r = 0.95), with all differences falling within the 95% limits of agreement. Overall, these results suggest that the CBMS is a valid tool to measure balance in CR patients and can be reliably administered by health care professionals with minimal training.


In vitro metabolic activation of the pulmonary toxin, 4-ipomeanol, in nonciliated bronchiolar epithelial (Clara) and alveolar type II cells isolated from rabbit lung.
The metabolism and covalent binding of 4-ipomeanol (IPO), a pulmonary toxin, were investigated in pulmonary cells isolated from rabbit. 3H-labeled IPO was incubated with freshly, isolated, intact alveolar type II cells (83% purity), nonciliated bronchiolar epithelial (Clara) cells (77% purity) and alveolar macrophages (greater than 90% purity). Covalent binding of radioactive material to type II and Clara cells was observed by autoradiography and by a biochemical method. IPO binding to cells was almost totally prevented by 1 mM piperonyl butoxide, an inhibitor of the cytochrome P-450-dependent metabolism of IPO. No covalent binding was observed with alveolar macrophages in the presence or absence of piperonyl butoxide. The maximal rates of enzyme-mediated covalent binding of IPO to protein were greater in the Clara cells (135 pmol/10(6) cells/min) than in the type II cells (13 pmol/10(6) cells/min). Incubation of either sonicated Clara or type II cell fractions with [3H]IPO, glutathione and NADPH (20 min, 37 degrees C) resulted in the formation of two distinct radiolabeled glutathione conjugates.


Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.
Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G(1)→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction.


The Type I IFN response to infection with Mycobacterium tuberculosis requires ESX-1-mediated secretion and contributes to pathogenesis.
The ESX-1 secretion system is a major determinant of Mycobacterium tuberculosis virulence, although the pathogenic mechanisms resulting from ESX-1-mediated transport remain unclear. By global transcriptional profiling of tissues from mice infected with either wild-type or ESX-1 mutant bacilli, we found that host genes controlled by ESX-1 in vivo are predominantly IFN regulated. ESX-1-mediated secretion is required for the production of host type I IFNs during infection in vivo and in macrophages in vitro. The macrophage signaling pathway leading to the production of type I IFN required the host kinase TANK-binding kinase 1 and occurs independently of TLR signaling. Importantly, the induction of type I IFNs during M. tuberculosis infection is a pathogenic mechanism as mice lacking the type I IFNR were more restrictive for bacterial growth in the spleen than wild-type mice, although growth in the lung was unaffected. We propose that the ESX-1 secretion system secretes effectors into the cytosol of infected macrophages, thereby triggering the type I IFN response for the manipulation of host immunity.


Serological evidence for infections with Borna disease virus in Turkey.
Distribution of Borna disease virus (BDV) infection outside endemic areas has been studied in several countries. We examined serum samples for anti-BDV antibodies in purebred racing horses and other domestic animals in Turkey. In total serum samples of 437 animals including 282 horses, 50 sheep, 25 goats, 50 cattle, and 30 cats were tested by indirect immunofluorescence assay (IFA). Anti-BDV antibodies were detected in 4.9% of horses, 12% of sheep, 4% of goats, 14% of cattle and 6.6% of cats. No statistical difference was observed between seroprevalence in Arabic and English purebred horses from four different racing centers (p > 0.05). Antibody titers ranged between 1:10 and 1:320. The highest antibody titers were found in sheep and horses and the lowest titer in cattle. Clinical symptoms of Borna disease were not observed in any animal of any species examined. This study confirms the presence of anti-BDV antibodies in racing horses as well as cat population in Turkey. Moreover anti-BDV antibodies are demonstrated for the first time in sheep, goats and cattle in Turkey.


Prognostic significance of mid- and post-ABVD PET imaging in Hodgkin's lymphoma: the importance of involved-field radiotherapy.
Although positron emission tomography (PET) response to chemotherapy (CT) has prognostic significance in Hodgkin's lymphoma (HL), it is unclear whether patients with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-PET positivity during and/or after CT can be rendered disease free with consolidative involved-field radiotherapy (IFRT). Patients with HL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)-based CT and radiotherapy (RT) at our institution from January 2000 to March 2007 were eligible. All patients had either a post-treatment PET or PET-CT before initiation of RT or a negative midtreatment PET or PET-CT. The primary end point was failure-free survival (FFS) for patients with and without residual FDG avidity after ABVD. The treatment outcome of patients with interim PET positivity during CT was also reported. Seventy-three patients were included in this study. Twenty patients (out of 46) were PET positive on interim PET, and 13 patients (out of 73) were PET positive at the conclusion of CT. At a median follow-up of 3.4 years for surviving patients, the 2-year FFSs for patients PET-negative versus PET-positive disease after ABVD were 95% and 69%, respectively (P < 0.01). On bivariable Cox regression, post-ABVD positivity (hazard ratio 4.8, P = 0.05) was predictive of disease recurrence after controlling for bulky disease. Of the 20 patients with interim PET positivity, three recurred, with a 2-year FFS of 85%. Among the 13 patients with interim PET positivity, but became PET negative at the completion of CT, the 2-year FFS was 92%. Sixty-nine per cent of patients with residual FDG avidity after ABVD were free of disease after consolidative RT, indicating a majority of patients with persistent lymphoma can be cured by sterilizing this PET-positive disease.


Best evidence topic report. Aspirin in the treatment of acute pulmonary embolism.
A short cut review was carried out to establish whether aspirin is a useful adjunct in the treatment of acute pulmonary embolism. No papers were found using the reported search to answer the clinical question. A clinical bottom line is stated.


Colorectal cytology in chronic ulcerative colitis.
During a period of ten years, 109 colorectal cytology specimens were obtained from 41 patients with chronic ulcerative colitis. There were 28 male and 13 female patients, whose average age was 45 years. All patients were symptomatic and had ulcerative colitis with repeated attacks of profuse diarrhea on the average for 12 years prior to their first cytologic examination. Eight cytology specimens were positive for malignant cells, 35 had atypia, 58 were negative and 8 were unsatisfactory. The malignant cells showed marked anisocytosis, pleomorphism and nuclear hyperchromasia and appeared in loosely cohesive clusters or in single forms in an inflammatory and necrotic background. Subsequent colectomy revealed invasive carcinoma in five patients and carcinoma in situ in two. Smears that were negative or showed atypia contained abundant chronic inflammatory cells. The atypical colonic epithelial cells contained prominent nuclei and formed cohesive clusters. Surgical biopsy and/or segmental resection revealed the presence of polyps, pseudopolyps, polypoid hyperplasia, mucosal atypia and crypt abscesses in patients with atypical and negative cytologic findings. It is concluded that cytologic examination of the colon can play an important role in the examination of patients with ulcerative colitis and allows for the detection of malignant transformation of the colonic mucosa.


Ubiquinone limits oxidative stress in Escherichia coli.
Ubiquinone is an essential redox component of the aerobic respiratory chains of bacteria and mitochondria. It is well established that mammalian ubiquinone can function in its reduced form (ubiquinol) as a lipid-soluble antioxidant preventing lipid peroxidation. The objective of this study was to test the hypothesis that prokaryotic ubiquinone is involved in the defence against oxidative stress in the cytoplasmic membrane. The rate of superoxide production by rapidly respiring wild-type Escherichia coli membranes was twofold higher than in the slowly respiring membranes from a ubiCA knockout mutant. However, large amounts of superoxide accumulated in the Ubi- membranes compared to wild-type membranes, which possess superoxide-scavenging ubiquinol. Likewise, the rate of H2O2 production was twofold higher in the wild-type, but the overall production of H2O2 was again significantly higher in the Ubi- membranes. Inclusion of a water-soluble ubiquinone homologue (UQ-1) effectively decreased the amount of H2O2 produced in the Ubi- membranes in a concentration-dependent manner. Addition of UQ-2 to the membranes was even more effective in limiting accumulation of H2O2 than was UQ-1, suggesting a role for the side-chain in conferring liposolubility in the antioxidative defence mechanism. Intracellular H2O2 concentration was increased 1.8-fold in the ubiCA mutant, and expression of the katG gene, encoding the catalase hydroperoxidase I, as well as catalase enzyme activity, were increased twofold in this mutant. The ubiCA mutant was hypersensitive to oxidative stress mediated by CuSO4 or H2O2; sensitivity to the latter could be abolished by addition of cysteine. This phenotype was also exhibited by a ubiG mutant, defective in the last step of UQ biosynthesis and therefore expected to accumulate several UQ biosynthetic intermediates. These observations support the participation of reduced ubiquinone as an antioxidant in E. coli. The ubiCA mutant exhibited a pleiotropic phenotype, being resistant to heat, linolenic acid and phleomycin. Resistance to the two latter compounds is probably due to reduced uptake. Like mutants unable to synthesize the quinol oxidase, cytochrome bd, the ubiCA mutant was also sensitive to dithiothreitol, an effect that is attributed to inability of the respiratory chain to maintain an appropriate redox balance in the periplasm.


Use of Internet panels to conduct surveys.
The use of Internet panels to collect survey data is increasing because it is cost-effective, enables access to large and diverse samples quickly, takes less time than traditional methods to obtain data for analysis, and the standardization of the data collection process makes studies easy to replicate. A variety of probability-based panels have been created, including Telepanel/CentERpanel, Knowledge Networks (now GFK KnowledgePanel), the American Life Panel, the Longitudinal Internet Studies for the Social Sciences panel, and the Understanding America Study panel. Despite the advantage of having a known denominator (sampling frame), the probability-based Internet panels often have low recruitment participation rates, and some have argued that there is little practical difference between opting out of a probability sample and opting into a nonprobability (convenience) Internet panel. This article provides an overview of both probability-based and convenience panels, discussing potential benefits and cautions for each method, and summarizing the approaches used to weight panel respondents in order to better represent the underlying population. Challenges of using Internet panel data are discussed, including false answers, careless responses, giving the same answer repeatedly, getting multiple surveys from the same respondent, and panelists being members of multiple panels. More is to be learned about Internet panels generally and about Web-based data collection, as well as how to evaluate data collected using mobile devices and social-media platforms.


[Changes in the synaptosomal membrane in the modelling of the phototherapeutic action used in bilirubin encephalopathy].
Continuous irradiation of bilirubin containing (3.10(-5) M) particles of the synaptosomal membrane (pH 7.2, at 10 degrees C) with blue light for 2 hours led to decrease of the total specific activity of ATPase, specific activity of Na, K-ATPase, and (less significantly and at a slower rate) specific activity of acetilcholinesterase. Pre-irradiation argon barbotage of the aqueous suspension of the synaptosomal membrane particles or addition of tocopherol acetate to the suspension counteracted the irradiation induced decrease of the enzyme activity. A counteraction was also produced by pre-irradiation alkalization of the suspension to pH 7.8 at 10 degrees C or addition of serum albumin to the suspension; the character of the effect of this protein on the activity of the membrane enzymes in irradiation was determined by certain peculiarities of its chemical composition. The strongest counteraction to the irradiation induced decrease of enzyme activity occurred in addition of monomeric albumin, freed of organophilic ligands, when pH of the suspension was 7.8 (10 degrees C). The activity of Na, K-ATPase and acetylcholinesterase was reduced most markedly when monomeric ligand containing albumin was added to a suspension of membrane particles which was acidified to pH 6.8 (10 degrees C) before the beginning of irradiation.


Endothelium-dependent contractions: when a good guy turns bad!
Endothelial cells can induce contractions of the underlying vascular smooth muscle by generating vasoconstrictor prostanoids (endothelium-dependent contracting factor; EDCF). The endothelial COX-1 isoform of cyclooxygenase appears to play the dominant role in the phenomenon. Its activation requires an increase in intracellular Ca(2+) concentration. The production of EDCF is inhibited acutely and chronically by nitric oxide (NO), and possibly by endothelium-dependent hyperpolarizing factor (EDHF). The main prostanoids involved in endothelium-dependent contractions appear to be endoperoxides (PGH(2)) and prostacyclin, which activate thromboxane-prostanoid (TP) receptors of the vascular smooth muscle cells. Oxygen-derived free radicals can facilitate the production and/or the action of EDCF. Endothelium-dependent contractions are exacerbated by ageing, obesity, hypertension and diabetes, and thus are likely to contribute to the endothelial dysfunction observed in older people and in essential hypertensive patients.


Studies on the secondary structure of nuclear ribonucleic acids.
Rat liver nuclei were separated into two fractions, the nucleolus and the nucleoplasm, by a combined salt-enzymic extraction. RNA was purified from both sources and analysed on sucrose density gradients. In both fractions a prominent heterogeneous RNA class with mean sedimentation coefficient of 18S was found. This material was analysed by measuring the rate of reaction with formaldehyde, the ultraviolet absorbance-temperature profile, the spectrophotometric observation of conformational changes as a function of pH, the spectrophotometric titration of uracil and guanine residues and the effect of both temperature and ionic strength on the spectrophotometric titration of cytosine residues. Nucleoplasmic 18S RNA fraction exhibited, on heating and also by adjustment of the pH to 2.5, a hyperchromicity of about 16%, close to that observed, in control experiments, for ribosomal RNA (22%). Titration of cytosine residues in solutions containing 1mm-NaCl and 0.1m-NaCl yielded pK values equal to 4.41 and 3.84 respectively. These results suggest that this RNA fraction is composed of structurally complex polymers. The hypochromicity of the nucleolar 18S RNA fraction determined by heating or adjusting the pH to 2.5, was not greater than 6% of the initial value. The rate of reaction with formaldehyde was 88% of that observed for the hydrolysed 18S fraction which suggested only 12% hydrogen bonding. pK values for uracil and guanine residues were 10.1 and 10.05 respectively. Titration of cytosine residues yielded a pK of 4.10, which was found to be independent of temperature and ionic strength variations.


Improving the quality of care for Medicaid patients with chronic diseases: Community Care of North Carolina.
Community Care of North Carolina's provider-driven approach to quality improvement has benefitted tens of thousands of North Carolinians with diabetes, asthma, hypertension, heart failure, and cardiovascular disease, and it has achieved better results than commercial Medicaid managed care nationally. Substantial opportunities remain, however, particularly for patients with complex care needs.


Renal denervation: a new therapeutic approach for resistant hypertension.
To review the advances in studies on renal denervation. References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. Articles with keywords "renal denervation" and "resistant hypertension" were selected. Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review. Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.


Formation of arrowhead complexes with heavy meromyosin in a variety of cell types.
Heavy meromyosin (HMM) forms characteristic arrowhead complexes with actin filaments in situ. These complexes are readily visualized in sectioned muscle. Following HMM treatment similar complexes appear in sectioned fibroblasts, chondrogenic cells, nerve cells, and several types of epithelial cells. Thin filaments freshly isolated from chondrogenic cells also bind HMM and form arrowhead structures in negatively stained preparations. HMM-filament complexes are prominent in the cortex of a variety of normal metaphase and Colcemid-arrested metaphase cells. There is no detectable binding of HMM with other cellular components such as microtubules, 100-A filaments, tonofilaments, membranes, nuclei, or collagen fibrils. The significance of HMM-filament binding is discussed in view of the finding that arrowhead complexes form in types of cells not usually thought to contain actin filaments.


Developmental Coordination Disorder Affects the Processing of Action-Related Verbs.
Processing action-language affects the planning and execution of motor acts, which suggests that the motor system might be involved in action-language understanding. However, this claim is hotly debated. For the first time, we compared the processing of action-verbs in children with Developmental Coordination Disorder (DCD), a disease that specifically affects the motor system, with children with a typical development (TD). We administered two versions of a go/no-go task in which verbs expressing either hand, foot or abstract actions were presented. We found that only when the semantic content of a verb has to be retrieved, TD children showed an increase in reaction times if the verb involved the same effector used to give the response. In contrast, DCD patients did not show any difference between verb categories irrespective of the task. These findings suggest that the pathological functioning of the motor system in individuals with DCD also affects language processing.


Wound fluid in diabetic foot ulceration: more than just an undefined soup?
Valid and reproducible sampling techniques as well as processing protocols are required for the assessment of biomarkers and mediators contained in wound exudate. Moreover, the ideal technique should be easy to use even in daily clinical routine. This is challenging since wound fluid represents an inhomogeneous mixture of different exogenous and endogenous sources. Analyzing wound fluid, however, may facilitate clinical decision making. Many techniques for obtaining wound fluid have been described. There is very little validation data, and the array of different techniques appears confusing. Structuring and new standards are needed to avoid wound fluid sampling yielding an "undefined soup." A lot of wound fluid parameters have been analyzed, although none of them have made its way into clinical practice. Nevertheless, basic principles of wound healing have been established from wound fluid analysis. With adequate techniques suitable for daily practice, basic research might foster our clinical understanding of wound healing with implications for new therapies. So far, research has mainly concentrated on analyzing available sample material with respect to either a wide variety of analytes or comparing acute with chronic wound exudate. Clinical endpoints such as healing or wound infection as well as longitudinal data may indeed be more valuable for clinical practice, enabling the discovery of meaningful biomarkers using a suitable technique.


Geographic variation in human mitochondrial DNA control region sequence: the population history of Turkey and its relationship to the European populations.
The hypervariable segment I of the control region of the mtDNA (positions 16024-16383) was amplified from hair roots by PCR and sequenced in 45 unrelated individuals from Anatolia (Asian Turkey). Forty different sequences were found, defined by 56 variable positions, of which only one involves a transversion. The neighbor-joining tree of Kimura's distance matrix for all sequences shows four main clusters. Cluster D was found to be the most statistically robust of the four, and all the sequences in it shared a mutation that is present only in European and West Asian populations. The variability in cluster D could have originated between 37,000 and 107,000 years ago. No branch is unexpectedly long, denoting the absence of sequences that diverged much before the others. The pairwise difference distribution is bell-shaped, in accordance with a population expansion occurring roughly 35,000 to 100,000 years ago. When compared to other Caucasoid populations through the pairwise difference distribution, there is a pattern from the Middle East (older expansion) to the various European populations, with Turkey in an intermediate position; when Turkish sequences are compared through a neighbor-joining tree on a genetic distance matrix of populations, this position is again evidenced. Although there is a very low level of genetic divergence among Caucasoid populations as shown by mtDNA control region sequences, a geographic pattern of genetic variation emerges, denoting a stepping-stone position of Turkey between the Middle East and Europe, which is in agreement with the hypothesis of a replacement of Neanderthals by modern humans, which could be related to the Upper Paleolithic cultural expansion.


High-resolution 3D models of Caulobacter crescentus chromosome reveal genome structural variability and organization.
High-resolution three-dimensional models of Caulobacter crescentus nucleoid structures were generated via a multi-scale modeling protocol. Models were built as a plectonemically supercoiled circular DNA and by incorporating chromosome conformation capture based data to generate an ensemble of base pair resolution models consistent with the experimental data. Significant structural variability was found with different degrees of bending and twisting but with overall similar topologies and shapes that are consistent with C. crescentus cell dimensions. The models allowed a direct mapping of the genomic sequence onto the three-dimensional nucleoid structures. Distinct spatial distributions were found for several genomic elements such as AT-rich sequence elements where nucleoid associated proteins (NAPs) are likely to bind, promoter sites, and some genes with common cellular functions. These findings shed light on the correlation between the spatial organization of the genome and biological functions.


Tumor-like lesions in the mantle of the mussel Modiolus difficilis from the Sea of Japan.
Two inner growths in the mantle beneath the epithelium were found in 1 of 1000 mussels Modiolus difficilis from Amursky Bay, Sea of Japan, within the city precincts of Vladivostok. Both growths were about 2000 microns in maximal diameter in section and elevated slightly above the mantle surface. The mantle epithelium near the growths formed deep invaginations, and clusters of mucous cells were numerous beneath the epithelium. Histological and histochemical methods were employed. Two different kinds of growth were revealed. The off-white growth consisted of cells with thin granular or vesicular cytoplasm containing glucosaminoglycans, proteins and a small amount of neutral polysaccharides. Growth cells were pure white in color after treatment of preparations with 1% H2SO4 and differed markedly from the mantle cells. The yellow growth consisted of large granular cells with neutral polysaccharides and proteins. Although growths were composed of different kinds of cells, they seemed to be derived from subepithelial mucous cells. This was supported by histological and histochemical staining reactions of some tumor and mantle epithelial cells. Mitotic indices (MI) of growths and subepithelial mucous cells were zero, MI of ciliated mantle epithelium reached 0.07%. The lesions were areas of strongly altered mucous cells of mantle epithelium and were non-neoplastic.


High prevalence of the His63Asp HFE mutation in Italian patients with porphyria cutanea tarda.
Sporadic porphyria cutanea tarda (PCT) is caused by a reduced activity of uroporphyrinogen decarboxylase (URO-D) in the liver. Mild to moderate iron overload is common in PCT, as iron is one of the factors which trigger the clinical manifestations of the disease through the inactivation of URO-D. A role for genetic hemochromatosis in the development of iron overload in sporadic PCT has been hypothesized in the past. The aim of this work was to investigate whether mutations of HFE, which is a candidate gene for hemochromatosis, play the role of genetic susceptibility factors for PCT in Italian patients, who have a high prevalence of acquired triggering factors, such as hepatitis C virus (HCV) chronic infection and alcohol. We determined HFE genotypes of 68 male patients with PCT. Our data do not confirm an association of PCT with the Cys282Tyr HFE mutation, strongly associated with hemochromatosis in Northern European countries. A second mutation of HFE, His63Asp, however, had a significantly increased frequency as it was present in half of the patients. Surprisingly, the presence of the His63Asp mutation was not related to the iron status of patients, suggesting that a subtle abnormality of iron metabolism induced by this mutation could escape detection by the standard parameters of iron status. In PCT patients with liver disease, the presence of the mutation could contribute to the inactivation of URO-D, either directly or through a synergistic action with other factors that cause liver damage.


Joint Associations of Pregnancy Complications and Postpartum Maternal Renal Biomarkers With Severe Cardiovascular Morbidities: A US Racially and Ethnically Diverse Prospective Birth Cohort Study.
Background Pregnancy complications are risk factors for cardiovascular disease (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in combination with pregnancy complications, in predicting subsequent severe maternal CVD. Methods and Results This study included 566 mothers of diverse races and ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively. Plasma creatinine and CysC (cystatin C) were measured 1 to 3 days after delivery. CVD during follow-up was defined by physician diagnoses in electronic medical records. Associations of renal biomarkers and pregnancy complications with time-to-CVD events were assessed using Cox proportional hazards models. During an average of 10.3±3.2 years of follow-up, 30 mothers developed 1 or more CVDs. Only a modest association was observed between creatinine and risk of CVD. In comparison, we found that per 0.1 mg/L increase of CysC was associated with a hazard ratio (HR) of 1.2 (95% CI, 1.1-1.4) for CVD after adjusting for covariates. Compared with those without preeclampsia and with normal CysC level (≤75th percentile), mothers with preeclampsia and elevated CysC (>75th percentile) had the highest risk of CVD (HR, 4.6 [95% CI, 1.7-17.7]), whereas mothers with preeclampsia only or with elevated CysC only did not have significantly increased CVD risk. Similar synergistic effects for CVD were observed between CysC and preterm delivery. Conclusions In this sample of US, traditionally underrepresented multiracial and multiethnic high-risk mothers, elevated maternal plasma CysC, independently and jointly with pregnancy complications, increased risk of CVD later in life. These findings warrant further investigation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03228875.


[Psychopathology in medically refractory partial seizures].
Today, psychopathology in medically refractory partial seizures is well-known. Descriptive (syndromic) classifications of both epileptic syndromes and psychiatric disturbances associated with prospective psychiatric status evaluations in resective epilepsy surgery centers in order to prevent poor post surgical outcome have increased our knowledge of the mental status of these patients. Three major categories of psychiatric comorbidities are observed. 1. Specific post ictal syndromes related to seizures (post ictal psychoses and post ictal depressive disorders). 2. Interictal psychiatric disorders: depression appears to be the most prevalent psychiatric condition in medically refractory seizures followed by anxiety and psychotic states. 3. Psychiatric adverse events of antiepileptic drugs according to the numerous new available drugs. There are no published guidelines. We are challenged both as clinicians and as an academic community. We need to improve identification, better utilize existing therapies and promote the development of prospective trials devoted to the study of psychiatric status in presurgical evaluation. A psychiatrist must be included in presurgical teams.


Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors.
Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in young children and the elderly. There are currently no licensed RSV vaccines, and passive prophylaxis with the monoclonal antibody palivizumab is restricted to high-risk infants in part due to its modest efficacy. Although it is widely agreed that an effective RSV vaccine will require the induction of a potent neutralizing antibody response against the RSV fusion (F) glycoprotein, little is known about the specificities and functional activities of RSV F-specific antibodies induced by natural infection. Here, we have comprehensively profiled the human antibody response to RSV F by isolating and characterizing 364 RSV F-specific monoclonal antibodies from the memory B cells of three healthy adult donors. In all donors, the antibody response to RSV F is comprised of a broad diversity of clones that target several antigenic sites. Nearly half of the most potent antibodies target a previously undefined site of vulnerability near the apex of the prefusion conformation of RSV F (preF), providing strong support for the development of RSV vaccine candidates that preserve the membrane-distal hemisphere of the preF protein. Additionally, the antibodies targeting this new site display convergent sequence features, thus providing a future means to rapidly detect the presence of these antibodies in human vaccine samples. Many of the antibodies that bind preF-specific surfaces are over 100 times more potent than palivizumab, and several cross-neutralize human metapneumovirus (HMPV). Taken together, the results have implications for the design and evaluation of RSV vaccine candidates and offer new options for passive prophylaxis.


Surface tension of root canal irrigants.
The aim of this study was to evaluate the surface tension values of established and potential endodontic irrigants to which a surface active agent had not been added. Additionally, Cetredixine, a surfactant-containing 0.2% chlorhexidine gluconate solution, was included in the measurements. Surface tension measurements were performed using the ring method on a DuNouy tensiometer at a standard room temperature. Ringer's solution, saline solution, and distilled water had the highest surface tension values, whereas those of NaOCl (2.5% and 5%) and 17% EDTA were relatively low. Two anesthetic solutions, Ultracaine and Citanest, demonstrated values similar to NaOCl and EDTA, although a statistically significant difference was found between all solutions tested. Cetredixin displayed the lowest surface tension. A low surface tension agent should penetrate tubules better.


Confidence and Training of Speech-Language Pathologists in Cognitive-Communication Disorders: Time to Rethink Graduate Education Models?
Purpose The purpose of this article is to highlight the need for increased focus on cognitive communication in North American speech-language pathology graduate education models. Method We describe key findings from a recent survey of acute care speech-language pathologists (SLPs) in the United States and expand upon the ensuing discussion at the 2020 International Cognitive-Communication Disorders Conference to consider some of the specific challenges of training for cognitive communication and make suggestions for rethinking how to prepare future clinicians to manage cognitive-communication disorders. Results Results from the survey of acute care SLPs indicated inconsistent confidence and training in managing cognitive-communication disorders. We discuss the pros and cons of several avenues for improving the consistency of cognitive-communication training, including a standalone cognitive-communication course, integrating cognitive communication in all courses across the speech-language pathology undergraduate and graduate curriculum, and using problem-based learning frameworks to better prepare students as independent thinkers in the area of cognitive communication and beyond. Conclusions Cognitive-communication disorders cut across clinical diagnoses and settings and are one of the largest and fastest growing parts of the SLP's scope of practice. Yet, surveys, including the one discussed here, have repeatedly indicated that SLPs do not feel prepared or confident to work with individuals with cognitive-communication disorders. We propose several avenues for increasing educational emphasis on cognitive communication. We hope these ideas will generate discussion and guide decision making to empower SLPs to think critically and step confidently into their roles as leaders in managing the heterogeneous and ever-growing populations of individuals with cognitive-communication disorders.


Self-Compassion: Theory, Method, Research, and Intervention.
Self-compassion refers to being supportive toward oneself when experiencing suffering or pain-be it caused by personal mistakes and inadequacies or external life challenges. This review presents my theoretical model of self-compassion as comprised of six different elements: increased self-kindness, common humanity, and mindfulness as well as reduced self-judgment, isolation, and overidentification. It discusses the methodology of self-compassion research and reviews the increasingly large number of empirical studies that indicate self-compassion is a productive way of approaching distressing thoughts and emotions that engenders mental and physical well-being. It also reviews research that dispels common myths about self-compassion (e.g., that it is weak, selfish, self-indulgent or undermines motivation). Interventions designed to increase self-compassion, such as compassion-focused therapy and mindful self-compassion, are discussed. Finally, the review considers problematic issues in the field, such as the differential effects fallacy, and considers limitations and future research directions in the field of self-compassion research.


A community-based randomized controlled trial of iron and zinc supplementation in Indonesian infants: effects on growth and development.
Deficiencies of iron and zinc are associated with delayed development, growth faltering, and increased infectious-disease morbidity during infancy and childhood. Combined iron and zinc supplementation may therefore be a logical preventive strategy. The objective of the study was to compare the effects of combined iron and zinc supplementation in infancy with the effects of iron and zinc as single micronutrients on growth, psychomotor development, and incidence of infectious disease. Indonesian infants (n = 680) were randomly assigned to daily supplementation with 10 mg Fe (Fe group), 10 mg Zn (Zn group), 10 mg Fe and 10 mg Zn (Fe+Zn group), or placebo from 6 to 12 mo of age. Anthropometric indexes, developmental indexes (Bayley Scales of Infant Development; BSID), and morbidity were recorded. At 12 mo, two-factor analysis of variance showed a significant interaction between iron and zinc for weight-for-age z score, knee-heel length, and BSID psychomotor development. Weight-for-age z score was higher in the Zn group than in the placebo and Fe+Zn groups, knee-heel length was higher in the Zn and Fe groups than in the placebo group, and the BSID psychomotor development index was higher in the Fe group than in the placebo group. No significant effect on morbidity was found. Single supplementation with zinc significantly improved growth, and single supplementation with iron significantly improved growth and psychomotor development, but combined supplementation with iron and zinc had no significant effect on growth or development. Combined, simultaneous supplementation with iron and zinc to infants cannot be routinely recommended at the iron-to-zinc ratio used in this study.


Validation and Reproducibility of Total Plaque Thickness in Carotid and Femoral Arteries Using Ultrasound.
Plaque burden quantification by ultrasound improves cardiovascular (CV) risk prediction. However, measuring total plaque volume (TPV) with 3-D ultrasound, the current gold standard, is time consuming. In the present study we investigated the reproducibility of weighted total plaque thickness (wTPT) measured by 2-D ultrasound and its correlation with TPV. Participants in an ongoing study of subclinical atherosclerosis and CV risk with no known atherosclerotic CV disease but who were found to have one or more plaques in carotid or femoral arteries by 2-D ultrasound were included. A total of 34 women and 26 men (mean age: 59.4 y, standard deviation: 8.7) underwent primary 2-D and 3-D ultrasound examinations. Participants then underwent a 2-D ultrasound examination by another radiologist blinded to the first radiologist's findings. Finally, all participants underwent a follow-up 2-D ultrasound by the first radiologist. Comparison of wTPT measurements between the 2-D studies revealed no significant difference (mean difference: 0.29 mm, 95% confidence interval [CI]: -0.48 to 1.17). Inter-observer and intra-observer analyses revealed intraclass correlation coefficients of 0.97 (95% CI: 0.96-0.98) and 1.0 (95% CI: 0.99-1.00), respectively. wTPT correlated with TPV (Spearman's ρ = 0.98, 95% CI: 0.96-0.99). Elapsed time for assessing wTPT was less than that for TPV (mean difference: 36.1 min, 95% CI: 26.0-46.3). wTPT had high reproducibility and correlation with TPV while requiring substantially less time. Future studies addressing the role of wTPT in predicting CV disease are needed.


Antigen-specific immunoglobulin A antibodies secreted from circulating B cells are an effective marker for recent local immune responses in patients with cholera: comparison to antibody-secreting cell responses and other immunological markers.
Gut-derived lymphocytes transiently migrate through the peripheral circulation before homing back to mucosal sites and can be detected using an ELISPOT-based antibody secreting cell (ASC) assay. Alternatively, transiently circulating lymphocytes may be cultured in vitro, and culture supernatants may be assayed for antigen-specific responses (antibody in lymphocyte supernatant [ALS] assay). The ALS assay has not been validated extensively in natural mucosal infection, nor has the ALS response been compared to the ASC assay and other cholera-specific immunological responses. Accordingly, we examined immune responses in 30 adult patients with acute cholera in Bangladesh, compared with 10 healthy controls, measuring ALS-immunoglobulin A (IgA), ASC-IgA, and serum and fecal IgA responses to two potent Vibrio cholerae immunogens, the nontoxic B subunit of cholera toxin (CtxB) and lipopolysaccharide (LPS) and a weaker V. cholerae immunogen, the mannose-sensitive hemagglutinin (MSHA). We found significant increases of anti-CtxB, anti-LPS, and anti-MSHA IgA in supernatants of lymphocytes cultured 7 days after onset of cholera using the ALS assay. We found that ALS and ASC responses correlated extremely well; both had comparable sensitivities as the vibriocidal responses, and both procedures were more sensitive than fecal IgA measurements. An advantage of the ALS assay for studying mucosal immune responses is the ability to freeze antibodies in supernatants for subsequent evaluation; like the ASC assay, the ALS assay can distinguish recent from remote mucosal infection, a distinction that may be difficult to make in endemic settings using other procedures.


Chondropenia: current concept review.
The term "chondropenia" indicates the early stage of degenerative cartilage disease, and it has been identified by carefully monitoring early-stage osteoarthritis (OA). Not only is it the loss of articular cartilage volume, but it is also a rearrangement of biomechanical, ultrastructural, biochemical and molecular properties typical of healthy cartilage tissue. Diagnosing OA at an early stage or an advanced stage is valuable in terms of clinical and therapeutic outcome. In fact degenerative phenomena are supported by a complex biochemical cascade which unbalances the extracellular matrix homeostasis, closely regulated by chondrocytes. In the first stage an intense inflammatory reaction is triggered: pro-catabolic cytokines such as IL-1β and TNF-α triggering matrix metalloproteases and aggrecanase (ADAMT-4 and 5), responsible for the early loss of ultrastructural components, such as type II collagen and aggrecan. In addition nitric oxide and reactive oxygen species modulate the physiopathology of the condral matrix inducing apoptosis of chondrocytes through a mitochondria-dependent pathway. In addition, "Lonely Death": chondrocytes, are confined within a dense, avascular extracellular matrix capsule, and can trigger a genetically induced apoptosis and necrosis. The degenerative process starts from a central point and then spreads in a centrifugal manner in depth and in adjacent areas, eventually covering the whole joint; chondropenia represents a journey from the first clinically detectable time-point until it can be characterized as frank osteoarthritis. Currently, there are no instruments sensitive enough which allow a timely diagnosis of chondropenia. Innovative magnetic resonance imaging techniques, such as T2 mapping, can be effective and a sensitive diagnostic instrument for quantifying cartilage volume and proteoglycan content. However, avant-garde biophysical techniques, such as mechanical indenters, ultrasound and biochemical markers (uCTX-II), are rational and scientific tools applicable to the clinical and therapeutic management of early degenerative cartilage disease. The objective of this review on chondropenia is to present a state of the art and innovative concepts.


[Decision making concerning very old patients with deteriorating health living at home].
A woman aged 87 and three men aged 87, 86 and 83, respectively, lived at home or in an old-people's home, in poor physical condition due to old age and diseases such as COPD and heart failure. One man was demented, the others did not wish hospital admission in case of further deterioration. When the condition worsened due to infections and fractures, the GP to a limited extent performed diagnostics and treatment. The four patients died, three of them after admission and intensive treatment because the restricted policy had not been communicated clearly. In decision-making about the management of geriatric patients, it is important that the GP knows the patient's wishes, correctly assesses his physical condition and prognosis and communicates well with the patient's next of kin and other care-givers.


Dissecting aneurysms of the distal segment of the posterior inferior cerebellar arteries: clinical presentation and management.
Dissecting aneurysms of the distal segment of the PICA are rare. The purpose of this study was to evaluate the clinical presentations, imaging features, treatment options, and clinical outcomes of dissecting PICA aneurysms. Six patients with dissecting aneurysms in the distal segments of PICA were found in the database of a single medical center, from November 1996 to December 2008, and retrospectively evaluated. Treatment mode and follow-up clinical outcomes were analyzed. Five patients with dissecting PICA aneurysms presented with acute intracranial hemorrhage and 1 patient presented with a large mass from an intramural hematoma. All 5 patients with intracranial hemorrhage were treated with endovascular occlusion of both the dissecting PICA aneurysm and the distal parent artery. The patient with the intramural hematoma underwent surgical trapping with end-to-end anastomosis. In 1 patient, the dissecting aneurysm recurred twice within a 5 year 3 month period, despite endovascular occlusion of both the aneurysm and the parent artery. The clinical outcome postprocedure was excellent in all patients, without permanent neurologic complication. For the endovascular treatment of dissecting aneurysms in the distal PICA segments, we recommend occlusion of both the dissecting aneurysm and the parent artery to avoid leaving the point of initial intimal tear untreated. All of our patients had excellent clinical outcomes; however, our experience with recanalization illustrates the need for close follow-up of patients.


Injuries to appendage extremities and digit tips: A clinical and cellular update.
The regrowth of amputated appendage extremities and the distal tips of digits represent models of tissue regeneration in multiple vertebrate taxa. In humans, digit tip injuries, including traumatic amputation and crush injuries, are among the most common type of injury to the human hand. Despite clinical reports demonstrating natural regeneration of appendages in lower vertebrates and human digits, current treatment options are suboptimal, and are complicated by the anatomical complexities and functions of the different tissues within the digits. In light of these challenges, we focus on recent advancements in understanding appendage regeneration from model organisms. We pay special attention to the cellular programs underlying appendage regeneration, where cumulative data from salamanders, fish, frogs, and mice indicate that regeneration occurs by the actions of lineage-restricted precursors. We focus on pathologic states and the interdependency that exists, in both humans and animal models, between the nail organ and the peripheral nerves for successful regeneration. The increased understanding of regeneration in animal models may open new opportunities for basic and translational research aimed at understanding the mechanisms that support limb regeneration, as well as amelioration of limb abnormalities and pathologies.


Multiple microcarcinoids in a patient with long standing ulcerative colitis.
A male patient with a 17 year history of intractable ulcerative colitis of the entire type was treated by total proctocolectomy. Colonoscopy before surgery did not identify dysplasia. Histological examination of the resected colorectum revealed that, in addition to chronic inflammatory infiltrates, there were 21 areas of microcarcinoids located in the muscularis propria and in the superficial layer of the submucosa. Carcinoids may be more common than previously thought, and they may be a reactive phenomenon to a variety of factors in ulcerative colitis.


Evaluation of tolerance to Pierce's disease and Botrytis in transgenic plants of Vitis vinifera L. expressing the pear PGIP gene.
SUMMARY Polygalacturonase-inhibiting proteins (PGIPs) are plant cell-wall proteins that specifically inhibit fungal endo-polygalacturonases (PGs) that contribute to the aggressive decomposition of susceptible plant tissues. The inhibition of fungal PGs by PGIPs suggests that PGIPs have a role in plant tolerance to fungal infections and this has been observed in transgenic plants expressing PGIPs. Xylella fastidiosa, the causal agent of Pierce's disease (PD) in grapevines, has genes that encode cell-wall-degrading enzymes, including a putative PG. Therefore, we hypothesized that PGIP expression could confer tolerance against this bacterium as well as against the fungal pathogen Botrytis cinerea. To test this hypothesis, Vitis vinifera cvs. 'Thompson Seedless' and 'Chardonnay' were transformed to express pear fruit PGIP-encoding gene (pPGIP) under the control of the CaMV 35S promoter. Substantial pear PGIP (pPGIP) activity was found in crude extracts from leaves and in xylem exudate of transgenic lines obtained from independent transformation events, but not in untransformed controls. pPGIP activity was detected in xylem exudate of untransformed scions grafted on to transgenic rootstocks expressing pPGIP. Leaves of transgenic plants infected with B. cinerea had reduced rates of lesion expansion. The development of PD was delayed in some transgenic lines with increased pPGIP activity. PD-tolerant transgenic lines had reduced leaf scorching, lower Xylella titres and better re-growth after pruning than the untransformed controls.


[The interferon status in helminthiases. 3. Opisthorchiasis].
In 23 patients with Opisthorchis felineus infection, 4 in subacute and 19 in chronic stages of the disease (7 subclinical, 8 with cholepathy and 4 with gastroduodenitis) the blood levels of alpha-interferon (IF-alpha) and IF-gamma were measured using vesical stomatitis virus culture. In patients with subacute opisthorchiasis the blood contents of IF-alpha and IF-gamma were the same as in control-30 practically healthy people (640-1280, log2 9.73 +/- 0.19, and 128-256, log2 7.75 +/- 0.25 against 640-1280, log2 10.04 +/- 0.12 and 128-256, log2 7.47 +/- 0.13 respectively). In patients with chronic opisthorchiasis the levels of IF-alpha and IF-gamma were lower than in control (320-640, log2 8.68 +/- 0.28 and 32-128, log2 6.0 +/- 0.58, p less than 0.01 and p less than 0.01 respectively). Among the ones with the subclinical course of the infection the content of IF-alpha was lower than in control (320-1280, log2 9.31 +/- 0.27, p less than 0.05). Patients with cholepathy had lower levels of IF-alpha and IF-gamma than those with subclinical course of the infection (160-640, log2 8.55 +/- 0.24 and 16-64, log2 5.0 +/- 0.26, p less than 0.01, p less than 0.01 respectively). That seemed to be a sign of immunodepression in the chronic stage of the disease some way more prominent in cases with cholepathy. Immediately after praziquantel therapy interferon levels remained unchanged.


Pregaming and Emotion Regulation's Relationship to Alcohol Problems in College Students: A Cross-Sectional Study.
Pregaming is a high-risk drinking behavior associated with increased alcohol consumption and alcohol-related problems. Quantity of alcohol consumed does not fully explain the level of problems associated with pregaming; yet, limited research has examined factors that may interact with pregaming behavior to contribute to the experience of alcohol-related problems. The current study examined whether use of two emotion regulation strategies influence pregaming's contribution to alcohol-related problems. Undergraduates (N = 1857) aged 18-25 years attending 19 different colleges completed an online survey in 2008-2009. Linear mixed models were used to test whether emotion regulation strategies moderate the association between pregaming status (pregamers vs. non/infrequent pregamers) and alcohol-related problems, when controlling for alcohol consumption, demographic covariates, and site as a random effect. Greater use of cognitive reappraisal was associated with decreased alcohol problems. Expressive suppression interacted with pregaming status. There was no relationship between pregaming status and alcohol problems for students who rarely used expression suppression; however, the relationship between pregaming status and alcohol problems was statistically significant for students who occasionally to frequently used expression suppression. Findings suggest that the relationship between pregaming and alcohol-related problems is complex. Accordingly, future studies should utilize event-level methodology to understand how emotion regulation strategies influence alcohol-related problems. Further, clinicians should tailor alcohol treatments to help students increase their use of cognitive reappraisal and decrease their use of suppression.


Verification and clarification of patterns of sensory integrative dysfunction.
Building on established relationships between the constructs of sensory integration in typical and special needs populations, in this retrospective study we examined patterns of sensory integrative dysfunction in 273 children ages 4-9 who had received occupational therapy evaluations in two private practice settings. Test results on the Sensory Integration and Praxis Tests, portions of the Sensory Processing Measure representing tactile overresponsiveness, and parent report of attention and activity level were included in the analyses. Exploratory factor analysis identified patterns similar to those found in early studies by Ayres (1965, 1966a, 1966b, 1969, 1972b, 1977, & 1989), namely Visuodyspraxia and Somatodyspraxia, Vestibular and Proprioceptive Bilateral Integration and Sequencing, Tactile and Visual Discrimination, and Tactile Defensiveness and Attention. Findings reinforce associations between constructs of sensory integration and assist with understanding sensory integration disorders that may affect childhood occupation. Limitations include the potential for subjective interpretation in factor analysis and inability to adjust measures available in charts in a retrospective research.