Pain and/or Discomfort During Debracketing: A Review.
The topic of bracket removal and enamel integrity has been extensively investigated. Nevertheless, bracket removal, as far as pain and/or discomfort are concerned, is poorly delineated in the orthodontic literature, i.e., the scarcity of reports in this area is conspicuous. In fact, only six studies were retrieved upon a PubMed search. These clinical studies performed with metal brackets are presented in a chronological order in the present review. Pain and/or discomfort during bracket removal are urgently in need of additional studies. The orthodontists have to be well-informed and updated to convey all the aspects of this procedure to the patient.


[Preparation technique for SEM demonstration of the muscular system of the blood vessels and the granular juxtaglomerular cell complex in the kidney (author's transl)].
A technique for SEM demonstration as well of the muscular architecture in the media of the blood vessels, as the granular juxtaglomerular cell complex in the wall of the afferent arterioles in the kidney is described. This method consists in an incomplete maceration and washing process in vascular cast preparations.


Proliferating cell nuclear antigen and p53 protein expression in submucosal invasive colorectal carcinoma.
In some cases of early colorectal carcinoma, radical surgical resection might be required because of vessel invasion, distant metastasis, or inadequate surgical margin. To characterize submucosal invasive colorectal carcinoma, we investigated expression of PCNA and p53 protein. Sixty-seven patients who underwent curative resection of submucosal invasive colorectal carcinoma participated in this study. The PCNA labeling index (PCNA-LI) is determined at the deepest lesion of carcinoma. The expression of PCNA and p53 protein were analyzed according to clinicopathological factors. 1) The PCNA-LI was correlated to histological grade, depth of invasion or vessel invasion in polypoid type. 2) The flat type had significantly higher PCNA-LI (65.1+/-8.2%) and p53 protein expression (69.6%) than the polypoid type. 3) The PCNA-LI was higher in cases with lymph node metastasis than in these without lymph node metastasis. 4) Overexpression of the p53 protein was detected in all cases with liver metastasis. Our results suggest that in order to determine the treatment for the patients with submucosal invasive colorectal carcinoma, the expression of PCNA and p53 protein may be a useful biologic marker.


A novel endoscopic approach to anterior odontoid screw fixation: technical note.
Techniques for operative management for type II odontoid fractures have continuously been refined with anterior odontoid screw arthrodesis having a clear advantage in maintaining normal motion. We have refined the technique of odontoid screw fixation further with the introduction of an endoscopic approach developed by the senior author. The necks of two partially embalmed cadavers were slightly extended under fluoroscopic guidance to simulate a reduced, anteriorly displaced type II fracture. Using a guide wire, graduated plastic sheath and endoscopic guidance, a solid 45 mm bone screw was passed through the odontoid with the aid of biplanar fluoroscopy. There were no apparent complications and no damage to surrounding vital structures. Anterior screw fixation of the odontoid is an established technique that provides adequate fixation, but the procedure can be technically demanding secondary to awkward tissue retraction. We present a percutaneous technique that obviates the need for tissue retraction while achieving an excellent result with only a modicum of effort.


Novel nuclear protein ALC-INTERACTING PROTEIN1 is expressed in vascular and mesocarp cells in Arabidopsis.
Pod shattering is an agronomical trait that is a result of the coordinated action of cell differentiation and separation. In Arabidopsis, pod shattering is controlled by a complex genetic network in which ALCATRAZ (ALC), a member of the basic helix-loop-helix family, is critical for cell separation during fruit dehiscence. Herein, we report the identification of ALC-INTERACTING PROTEIN1 (ACI1) via the yeast two-hybrid screen. ACI1 encodes a nuclear protein with a lysine-rich domain and a C-terminal serine-rich domain. ACI1 is mainly expressed in the vascular system throughout the plant and mesocarp of the valve in siliques. Our data showed that ACI1 interacts strongly with the N-terminal portion of ALC in yeast cells and in plant cells in the nucleus as demonstrated by bimolecular fluorescence complementation assay. Both ACI1 and ALC share an overlapping expression pattern, suggesting that they likely function together in planta. However, no detectable phenotype was found in plants with reduced ACI1 expression by RNA interference technology, suggesting that ACI1 may be redundant. Taken together, these data indicate that ALC may interact with ACI1 and its homologs to control cell separation during fruit dehiscence in Arabidopsis.


Steroid hormone receptors in breast cancer management.
Estrogen and progesterone receptors (ER and PR) have now been studied in clinical breast cancer for more than 20 years. Positive receptor status correlates with favorable prognostic features including a lower rate of cell proliferation and histologic evidence of tumor differentiation. During the first several years after diagnosis, patients with ER-positive tumors tend to have a lower recurrence rate; however, this is balanced by a higher recurrence rate in subsequent years so that the overall prognostic significance of receptor status is modest. ER and PR have their greatest utility in predicting response to hormonal therapy, both in the adjuvant setting and for advanced disease. When the assay is done properly and cut-offs for ER-negativity and positivity are defined by clinical studies of patients treated with endocrine therapy, receptor status is very helpful in identifying groups of patients who are very unlikely to benefit from hormonal therapy. Tumors that express both ER and PR have the greatest benefit from hormonal therapy, but those containing only ER or only PR still have significant responses. Two types of estrogen receptors, ERalpha and ERbeta, have now been identified. Although there is considerable homology between these receptor forms, they appear to have important structural and functional differences that may be important for tissue and promoter-specific regulation of gene expression. These receptor forms, as well as ER variants and mutants, may also contribute to hormonal sensitivity and resistance. PR also exists in two forms, PRA and PRB. PRA appears to have repressor functions on both PRB and ERalpha, and the ratio of PRA to PRB in clinical breast tumors needs to be studied for its possible clinical relevance. Expression of receptor-interacting proteins can also modulate ER transcriptional activity, and these too need additional study to determine if they are markers of hormonal sensitivity or resistance. In summary, ER and PR status are important biomarkers that help physicians individualize therapy.


Improved data analysis for the MinION nanopore sequencer.
Speed, single-base sensitivity and long read lengths make nanopores a promising technology for high-throughput sequencing. We evaluated and optimized the performance of the MinION nanopore sequencer using M13 genomic DNA and used expectation maximization to obtain robust maximum-likelihood estimates for insertion, deletion and substitution error rates (4.9%, 7.8% and 5.1%, respectively). Over 99% of high-quality 2D MinION reads mapped to the reference at a mean identity of 85%. We present a single-nucleotide-variant detection tool that uses maximum-likelihood parameter estimates and marginalization over many possible read alignments to achieve precision and recall of up to 99%. By pairing our high-confidence alignment strategy with long MinION reads, we resolved the copy number for a cancer-testis gene family (CT47) within an unresolved region of human chromosome Xq24.


Hot-spot relaxation time current dependence in niobium nitride waveguide-integrated superconducting nanowire single-photon detectors.
We investigate how the bias current affects the hot-spot relaxation dynamics in niobium nitride. We use for this purpose a near-infrared pump-probe technique on a waveguide-integrated superconducting nanowire single-photon detector driven in the two-photon regime. We observe a strong increase in the picosecond relaxation time for higher bias currents. A minimum relaxation time of (22 ± 1) ps is obtained when applying a bias current of 50% of the switching current at 1.7 K bath temperature. We also propose a practical approach to accurately estimate the photon detection regimes based on the reconstruction of the measured detector tomography at different bias currents and for different illumination conditions.


[Perioperative management of new antiplatelet drugs].
The management of antiplatelet drugs in the perioperative setting is based on an individual evaluation of the thrombotic and bleeding risks. When the bleeding risk is deemed low, continuation of the dual antiplatelet therapy is usually recommended, especially in high thrombotic risk settings. When the bleeding risk is deemed moderate, at least one antiplatelet agent should be continued, usually aspirin, and clopidogrel and ticagrelor should be discontinued 5 days and prasugrel 7 days before surgery. In some rare instances of high bleeding risk, discontinuation of aspirin 3 days before surgery is usually acceptable. In high thrombotic settings, bridging with an intravenous antiplatelet drug with a short half-life may be considered.


Diversity and distribution of avian haematozoan parasites in the western Indian Ocean region: a molecular survey.
The genetic diversity of haematozoan parasites in island avifauna has only recently begun to be explored, despite the potential insight that these data can provide into the history of association between hosts and parasites and the possible threat posed to island endemics. We used mitochondrial DNA sequencing to characterize the diversity of 2 genera of vector-mediated parasites (Plasmodium and Haemoproteus) in avian blood samples from the western Indian Ocean region and explored their relationship with parasites from continental Africa. We detected infections in 68 out of 150 (45·3%) individuals and cytochrome b sequences identified 9 genetically distinct lineages of Plasmodium spp. and 7 lineages of Haemoproteus spp. We found considerable heterogeneity in parasite lineage composition across islands, although limited sampling may, in part, be responsible for perceived differences. Two lineages of Plasmodium spp. and 2 lineages of Haemoproteus spp. were shared by hosts in the Indian Ocean and also on mainland Africa, suggesting that these lineages may have arrived relatively recently. Polyphyly of island parasites indicated that these parasites were unlikely to constitute an endemic radiation and instead probably represent multiple colonization events. This study represents the first molecular survey of vector-mediated parasites in the western Indian Ocean, and has uncovered a diversity of parasites. Full understanding of parasite community composition and possible threats to endemic avian hosts will require comprehensive surveys across the avifauna of this region.


Antioxidant and anti-inflammatory activity of Potentilla reptans L.
Potentilla species have been used in traditional medicine in the treatment of different ailment, disease or malady. Potentilla reptans (P. reptans) has been scarcely studied. The aim of this study was to test antioxidant and anti-inflammatory activity of P. reptans aerial part and rhizome. DPPH assay was used to measure antioxidant activity of aqueous plant extracts. Anti-inflammatory effect was evaluated by experimental animal model of phenol-in-acetone induced mice ear edema. DPPH radical-scavenging activity of both tested extracts was concentration dependent with IC50 values 12.11 μg/mL (aerial part) and 2.57 μg/mL (rhizome). Maximum anti-inflammatory effect (61.37%) was observed after administration of 10 mg/ear of the rhizome extract and it was 89.24% of effect induced by dexamethasone as a standard. In conclusion, P. reptans rhizome aqueous extract possesses anti-inflammatory effect and higher antioxidant activity than aerial part.


Performance of an optimally filled discontinuous bioreactor degrading 4-chlorophenol.
The stability of a fed-batch bioreactor operated with a new control strategy (ED-TOC) during a long-term period was evaluated. The ED-TOC strategy uses solely measurements of DO concentration and volume of the reactor to control the influent flow rate, and so the substrate degradation rate oscillates around its maximal value during the whole filling phase. The bioreactor was tested for the degradation of a wastewater containing 4-chlorophenol (4CP) as a model of an inhibitory compound. The experiment was conducted twice in order to investigate whether results were reproducible. Each set of experiments consisted of two phases: acclimation of the biomass to 4-chlorophenol and operation using the ED-TOC strategy. The main conclusion is that the reactor operated by the ED-TOC strategy is robust and stable in large operation periods. Degradation efficiencies greater than 99% as 4CP and greater than 97% as COD degradation were obtained. Toxicity analysis demonstrates that the bioreactor operated by ED-TOC eliminates the toxicity in the wastewater. Community analysis by DGGE was also conducted.


Model selection and sensitivity analysis for sequence pattern models.
In this article we propose a maximal a posteriori (MAP) criterion for model selection in the motif discovery problem and investigate conditions under which the MAP asymptotically gives a correct prediction of model size. We also investigate robustness of the MAP to prior specification and provide guidelines for choosing prior hyper-parameters for motif models based on sensitivity considerations.


Tenofovir-induced Leukocytoclastic Vasculitis.
Tenofovir, a nucleotide analog, is one of the first-line medications recommended for the treatment of active chronic hepatitis B virus infection (CHB) and as a primary prophylaxis to prevent hepatitis B reactivation in cases of immunosuppression. We report the first case of tenofovir-induced leukocytoclastic vasculitis (LCV). A 43-year-old obese woman, who was known to have inactive CHB, was diagnosed with chronic immune thrombocytopenic purpura (ITP). She was treated with corticosteroid therapy and was put on tenofovir to prevent hepatitis B virus reactivation. A month later, she developed a skin rash, described as non-blanchable well-defined erythematous to violaceous papules and targetoid patches in her lower extremities. A skin biopsy showed features of LCV. The rash resolved completely within few days after replacing tenofovir with entecavir.


Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis.
A host defense function for Alkaline phosphatases (ALPs) is suggested by the contribution of intestinal ALP to detoxifying bacterial lipopolysaccharide (endotoxin) in animal models in vivo and the elevation of ALP activity following treatment of human cells with inflammatory stimuli in vitro. However the activity of ALP in human plasma (primarily tissue-nonspecific ALP; TNAP) on lipopolysaccharide and other microbial products has not been assessed, nor has its expression been studied in preterm newborns, a vulnerable population at high risk of sepsis. In this context, the aim of our study was to characterize the activity of TNAP on Toll-like receptor (TLR) agonists and assess the concentrations of plasma ALP during late-onset sepsis in preterm newborns. Recombinant human TNAP was incubated with microbial products and phosphate release was measured by malachite green assay. Plasma ALP activity was measured serially in a cohort of preterm (N = 129) infants at high risk of late-onset sepsis (LOS). TNAP dephosphorylates poly-inosine:cytosine (Toll-like receptor (TLR) 3 agonist) and LPS from Klebsiella pneumoniae and Salmonella minnesota (TLR4 agonists). Plasma ALP significantly increased postnatally over the first 4 weeks of life in preterm and term newborns. Bacteremic LOS in preterm infants (gestational age ≤ 30 weeks) was associated with significantly elevated plasma ALP at 4 weeks postnatal age. TNAP, the main circulating isozyme of ALP, de-phosphorylates TLR agonists, demonstrates a post-natal age dependent increase in preterm and term plasma across the first 4 weeks of life, and is elevated in association with preterm LOS.


Post-traumatic compartment syndrome of the foot.
Post-traumatic compartment syndrome in the foot is an unusual but well-recognized entity. If there is an awareness of the condition at the time of presentation it can be diagnosed and treated effectively. A case of compartment syndrome in the foot of a 17-year-old boy after massive lower-extremity trauma is described. The simple and readily available diagnostic techniques are emphasized and an alternative approach to plantar decompression, which avoids exposure of and potential damage to the posterior tibial neurovascular bundle, is presented.


Changes in the Content of Pediatric Physical Therapy for Infants: A Quantitative, Observational Study.
The aim of our observational longitudinal study is to evaluate changes over time in standard pediatric physical therapy (PPT) for infants at risk of neurodevelopmental disorders. Treatment sessions in two time periods (2003-2005 [n = 22] and 2008-2014 [n = 16]) were video recorded and analyzed quantitatively in five categories: neuromotor actions, educational actions, communication, position, and situation of treatment session. Differences in percentages of time spent on therapeutic actions between periods were tested with Mann-Whitney U and Hodges Lehmann's tests. No significant changes appeared in the main categories of neuromotor actions. Time spent on not-specified educational actions toward caregivers (median from 99% to 81%, p = .042) and not-specified communication (median from 72% to 52%, p = .002) decreased. Consequently, time spent on specific educational actions (caregiver training and coaching; median from 1% to 19%, p = .042) and specific communication (information exchange, instruct, provide feedback; median from 21% to 38%, p = .007) increased. Infant position changed only minimally: time spent on transitions-that is, change of position-decreased slightly over time (median from 7% to 6%, p = .042). Situation of treatment session did not change significantly over time. Neuromotor actions in PPT remained largely stable over time. Specific educational actions and communication increased, indicating larger family involvement during treatment sessions.


Dielectric-lined cylindrical metallic THz waveguides: mode structure and dispersion.
Thin dielectric layers deposited on the inner surface of hollow cylindrical metallic waveguides for Terahertz (THz) waves reduce transmission losses below 1 dB/m. Impact of the dielectric layer on the waveguide dispersion is experimentally investigated by near-field mapping of guided short THz pulses at the input and the output of the waveguide. We obtain dispersion characteristics for the low-loss waveguide modes, the linearly-polarized HE(11) mode and the TE(01) mode, and compare the experimental results to the metallic waveguide dispersion. The additional dispersion due to the dielectric layer is found to be small for the HE(11) mode and the phase velocity is primarily determined by the waveguide radius.


Return to Sports and Recreational Activity After Single-Stage Bilateral Short-Stem Total Hip Arthroplasty: 5-Year Results of a Prospective Observational Study.
Single-stage bilateral total hip arthroplasty (THA) is an alternative to staged unilateral THA in patients suffering from bilateral hip arthritis; however, there is still broad concern regarding the safety and reliability of this procedure. Short-stem THA has emerged in recent years. To date, no data are available on sports and recreational activity levels after single-stage bilateral short-stem THA in the general patient population. Patients who have undergone single-stage bilateral short-stem THA return to a satisfying level of sports and recreational activity at midterm follow-up. Case series; Level of evidence, 4. A total of 54 consecutive patients (108 hips) were prospectively included. Midterm follow-up was performed in 51 patients (94.4%). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and the Harris Hip Score (HHS) were assessed clinically after a mean of 5.2 years. After a mean of 4.9 years, activity levels were assessed using the University of California, Los Angeles (UCLA) activity scale via a questionnaire. Additionally, a detailed evaluation of sports behavior was conducted using an additional questionnaire. Pain and satisfaction with sporting ability were assessed using a visual analog scale (VAS). Complications and revisions were documented. Patients had a mean WOMAC score of 98.0 (range, 60.0-100.0) and HHS score of 97.8 (range, 65.0-100.0) at final follow-up. The mean UCLA activity score was 4.7 (range, 2.0-10.0). An increasing number of patients were active in sports at follow-up compared with before surgery (76.5% vs 60.8%, respectively); 2 patients (3.9%) stopped participating in sports on a regular basis, and 10 (19.6%) commenced with sports after surgery. The most popular activities before surgery were cycling (31.4%), hiking (29.4%), swimming (21.6%), and fitness/weight training (15.7%). At follow-up, most patients were engaged in cycling (35.3%) and fitness/weight training (33.3%), followed by swimming (25.5%) and hiking (19.6%). The duration (hours per week) and frequency (times per week) of sporting activities remained stable. The mean VAS pain level during sports was 1.3 (range, 0.0-7.0). No revision surgery had to be performed. After single-stage bilateral short-stem THA, the study patients returned to satisfying levels of activity at midterm follow-up. Postoperatively, few patients were engaged in high-impact sports; however, more patients commenced with lower impact activities. Satisfaction with sporting abilities was high, and the complication rate in total was low.


Hospital structure and consumer satisfaction.
This study examines the relationship between hospital structural characteristics and patient satisfaction with hospital care. Teaching hospitals and private hospitals were expected to receive higher ratings of patient satisfaction than were nonteaching and government-controlled hospitals, because they generally are reputed to be technologically superior. Results show that, in general, most patients are satisfied with their hospital stays, but they are clearly more dissatisfied with their stays in teaching hospitals. Although a number of other correlates of patient satisfaction with the hospital stay are identified, no measure succeeds in reducing to insignificance the strong relationship between teaching status and dissatisfaction. Some suggestions are made as to why teaching hospital receive relatively poor evaluations from their patients.


Spatially tuned auditory responses in area LIP of macaques performing delayed memory saccades to acoustic targets.
1. The lateral intraparietal area (area LIP) of the macaque's posterior parietal cortex (PPC) lies in the dorsal stream of extrastriate visual areas. It receives extensive visual inputs and sends outputs to several eye movement centers. It contains neurons with visual and saccade-related responses suggesting a role of area LIP in programming saccadic eye movements to visual targets. Because primates can also orient to nonvisual stimuli, we investigated whether LIP neurons process stimuli of other modalities besides the visual one by comparing their activity in auditory and visual saccade tasks. 2. We recorded the activity of single neurons of Macaca mulatta monkeys while they performed memory saccades to acoustic and visual targets. We analyzed the activity during stimulus presentation (stimulus period, S) and during the delay (memory period, M) between stimulus presentation and the saccade to its remembered location. 3. Among 80 area LIP neurons tested, we found 44 that had S period and/or M period responses following presentation of the auditory stimulus. Most of these responses were spatially tuned, i.e., selective for the left or right stimulus location (27 of 29 S responses; 25 of 29 M responses). 4. The majority of neurons with responses in the auditory memory saccade task also responded in the visual version of the task. Eighty-nine percent (24/27) were clearly bimodal in the S period, and 88% (23/26) were bimodal in the M period. 5. Almost all the neurons with spatially tuned auditory responses that were bimodal were also spatially tuned in their visual responses (20/22 for S responses; 18/19 for M responses). The spatial tuning for the two modalities was the same in 85% (17/20) of the tested neurons for the S responses, and in 83% (15/18) of the tested neurons for the M responses. 6. Area LIP contains a population of neurons that respond to both visual and auditory stimuli. This result is consistent with our finding that the memory activity of many LIP cells encodes the next planned saccade. If cells are coding planned movements, they should be active independently of the sensory modality of the target for the movement, as was the case for most of the neurons described in the present study.


Infra-inguinal arterial reconstruction for peripheral arterial disease: the Curaçao experience.
The prevalence and treatment of peripheral arterial disease in the Caribbean is not well documented. The aim of this study was to review the results from a small hospital in the Caribbean. One-hundred and eight infra-inguinal arterial reconstructions on 90 patients were retrospectively reviewed Patients were classified according to the categories suggested by the Ad Hoc Committee on Reporting Standards of the Joint Councils of the Society for Vascular Surgery. Follow-up ranged from 0 to 103.1 months. The Kaplan-Meier method was used to visualize survival, limb salvage rates and primary and secondary patency rates. Cox regressions were used to identify potential risk factors. The limb salvage rates were 74.5% after one year and 71.4% after five years. Overall primary patency rates were 67.0 % after one year, 63.4% after three years and 50.8 % after five years. Overall secondary patency rates were 86.4% after one year and 75.1% after five years. The primary patency rate for autologous saphenous vein was 82.4% (SE 7.5%) after five years. The primary patency rates for prosthetic grafts were 62.1% (SE 8.5%) after one year; 56.9% (SE 9.2%) at three years and 37.9% (SE 16.7%) after five years. Infra-inguinal arterial bypass surgery is feasible in small Caribbean hospitals showing results comparable to major studies.


Studies on ribosome structure and interactions near the m62Am62A sequence.
Antibodies raised against N6, N6-dimethyl adenosine were used to study the environment and role of the m62Am62A sequences in the E. coli ribosome. It is observed that this sequence is exposed on the surface of isolated 30S subunits, but becomes inaccessible for IgG interaction upon heat activation. The m62Am62A sequence is also inaccessible for IgG interaction in 70S ribosomes or 30S subunits immediately after dissociation of 70S particles. The presence of IgGs results in a significant inhibition of IF3 binding to unactivated 30S particles. IF3 binding to activated 30S subunits is unaffected by the IgGs. Crosslinking of 30S proteins S18 and S21 with the bifunctional phenylene dimaleimide reagents results in a reduction in the extent of 30S-IgG interaction. From what is already known about the location of S18, S21 and the IF3 binding site, it is suggested that the m62Am62A sequence is located close to the initiator tRNA binding site of the 30S subunit during initiation of protein synthesis.


Near-infrared interactance (NIR): a new non-invasive technique to estimate subcutaneous body fat in newborns.
Body fat (BF) is rarely determined routinely in infants due to the lack of a simple measuring device. A portable NIR instrument, successfully applied in adults, takes 5 seconds for a measurement and involves no skin manipulation. We designed this study 1) to compare BF estimates by NIR to skinfold thickness (ST) and 2) to assess the relationship of NIR and ST values with standard measures reflecting BF, such as Weight/Length Ratio, Body Mass Index and Ponderal Index. We studied BF in 40 healthy term infants within 12 hours of birth by NIR and ST at 3 standard sites: triceps (TRI), subscapular (SUB) and abdominal (ABD). RESULTS. Significant correlations were found between NIR and ST (R=0.70, 0.58 and 0.64 for SUB, TRI and ABD, respectively); between the sums of the 3 measurements (R= 0.69), and between birthweight and ST (R=0.57) or NIR (0.51), and between Weight/Length Ratio and ST (R=0.55) or NIR (R=0.51). We conclude that NIR measurements correlate well with skinfold measurements and NIR can be measured faster than skinfolds (5 vs 60 seconds). We speculate that NIR could be cost-effective for routine clinical measure of body fat and growth in infants.


The incidence of birthmarks in the neonate.
The presence of various types of birthmarks was determined in 1,058 newborn infants under 72 hours of age. Of these, 79.5% were white, 6.2% were black, 11.2% were ladinos, and 2.6% were Asiatic. Mongol spots were present in 9.6% of the white babies, 95.5% of the black babies, 81% of the Asiatic babies, and 70.1% of ladino infants. Pigmented lesions were present in 42 (4%) of the infants. Biopsies obtained in 34 (3.2%) revealed that only one-third (11) of these were melanocytic nevi. Salmon patches were present in 40.3% of the infants, recognizable early strawberry marks in 2.6%, and port-wine strains in 0.3%. In addition to birthmarks, it was determined that 30.3% of the 508 babies examined at one of the two hospitals had toxic erythema of the newborn.


Mesentericocaval "jump" graft in management of portal hypertension: experience with 24 cases.
A series of 24 patients with cirrhosis have undergone mesentericocaval shunt operations for the relief of portal hypertension. Overall the results have been satisfactory. Four of the five patients treated as an emergency and 17 of the 19 who had the operation two to six weeks after haemorrhage had been controlled left hospital alive and well. Separation of the patients into three categories according to the findings of clinical and biochemical tests, however, showed that subsequent survival was satisfactory for patients in categories A and B but that all four patients in category C had died within one year after surgery. Assessment at three months showed that in three patients moderate hepatic encephalopathy had developed.Evidence that the shunt remains patent was shown by a low incidence of repeated gastrointestinal haemorrhage and a marked diminution in variceal size in 18 of the 19 cases examined serially. Radiographic techniques for confirming shunt patency were compared and cannulation of the graft via the femoral vein was found to provide a reliable and rapid means of assessment.


Targeting microparticle biogenesis: a novel approach to the circumvention of cancer multidrug resistance.
Microparticles (MPs) are released from most eukaryotic cells after the vesiculation of the plasma membrane and serve as vectors of long and short-range signaling. MPs derived from multidrug resistant (MDR) cancer cells carry molecular components of the donor cell such as nucleic acids and proteins, and can alter the activity of drug-sensitive recipient cells through the transfer of their cargo. Given the substantial role of MPs in the acquisition and dissemination of MDR, we propose that the inhibition of MP release provides a novel therapeutic approach. This study characterises the effect of a panel of molecules known to act on MP-biosynthetic pathways. We demonstrate a differential effect by these molecules on MP inhibition that appear dependent on the release of intracellular calcium stores following activation with the calcium ionophore A23187. Calpain inhibitor, PD-150606; a selective inhibitor of Rho-associated, coiled-coil containing protein kinase (ROCK), Y-27632; and the vitamin B5 derivative pantethine, inhibited MP release only upon prior activation with A23187. Calpain inhibitor II showed significant inhibition in the absence of cell activation, whereas the vitamin B5 derivatives cystamine dihydrochloride and cysteamine hydrochloride showed no effect on MP inhibition under either condition. In contrast the classical pharmacological inhibitor of MDR, the calcium channel blocker Verapamil, showed an increase in MP formation on resting cells. These results suggest a potential role for calcium in the mechanism of action for PD-150606, Y-27632 and pantethine. These molecules, together with calpain inhibitor II have shown promise as modulators of MP release and warrant consideration as potential candidates for the development of an alternative therapeutic strategy for the prevention of MP-mediated MDR in cancer.


Chapter 7: Nasal polyps.
Nasal polyps are inflammatory outgrowths of paranasal sinus mucosa caused by chronic mucosal inflammation that typically arise from the middle meatus and ethmoid region. The main symptoms of nasal polyps are perennial nasal congestion, nasal obstruction, and anosmia or hyposmia. Unlike patients with chronic rhinosinusitis (CRS) without nasal polyps who present with headache and facial pain, patients with nasal polyps typically do not complain of those symptoms. Nasal polyps appear as semitranslucent, pale gray growths in the nasal cavity in contrast to pink or erythematous adjacent mucosa. Nasal polyps occur more frequently in patients with persistent asthma, aspirin-exacerbated respiratory disease (AERD), CRS, and cystic fibrosis. Children with nasal polyps should be evaluated for cystic fibrosis. Churg-Strauss syndrome and ciliary dyskinesia also may be associated with nasal polyps. Nasal polyps have increased numbers of activated eosinophils, mast cells, and IgE. Staphylococcal superantigens may play a role in the Th2 type of chronic eosinophilic inflammation observed in nasal polyps. Dysfunction of the epithelial barrier in nasal polyps causing reduced levels of antimicrobial proteins has been described. Topical nasal steroids are the treatment of choice. They significantly decrease polyp size, nasal congestion, rhinorrhea, and increase nasal airflow. Short courses of oral steroids may be needed to reduce polyp size followed by maintenance therapy with intranasal steroids. Surgery is reserved for cases when polyps cause severe obstruction, recurrent sinusitis, and for patients who have failed medical therapy. Aspirin desensitization may decrease the requirement for polypectomies and sinus surgery in patients with AERD.


Local recurrence of breast cancer after cytological evaluation of lumpectomy margins.
Successful breast conservation therapy with optimal cosmesis requires adequate tumor excision and negative tumor margins. Therefore, more sensitive techniques are being developed to identify lumpectomy margins intraoperatively with greater accuracy. Unidentified microscopic disease is seemingly responsible for a local recurrence rate of up to 25 per cent 3 to 5 years after lumpectomy and radiotherapy for breast cancer patients. As a result, Moffitt Cancer Center has routinely used an intraoperative touch preparation cytology (TPC) protocol to evaluate the entire resected surface of all lumpectomies. In addition, resection margins were also evaluated by gross examination and by standard histology. In rare instances frozen sections were used to evaluate tumor margins. In this study 701 consecutive lumpectomy specimens were evaluated by TPC during the period of 9 years with a mean follow-up of 3.5 years. Local cancer recurrence was 2.7 per cent (mean recurrence, 2.53 years), in women whose lumpectomy margins were evaluated by TPC. Of interest, a local recurrence rate of 14.6 per cent was observed in patients who had referral lumpectomies evaluated by conventional histopathology. This study suggests that accurate margin assessment with TPC plays an important role in the control of local recurrence after breast conservation therapy. Therefore, we conclude the routine use of intraoperative TPC provides rapid, reliable, topographically accurate identification of residual microscopic disease at lumpectomy margins.


Failure of low temperature to arrest degradation of 14C-adenosine 5'-diphosphate by human plasma in the presence of EDTA.
Degradation of 14C-ADP in human platelet-rich and platelet-poor plasmas was studied. Three procedures were tested to determine which method was most effective in "stopping" enzyme reactions. One involved the immediate addition of perchloric acid to the reaction mixture at the end of the incubation period. Another involved "stopping" enzyme reactions at 0 degree C for about 20 min before the addition of perchloric acid. The third involved adding EDTA (10 mM final concentration) to "stop" the reactions at the end of incubation. The protein-free extracts from the plasmas were processed for adenine nucleotide assays by thin-layer chromatography. Addition of perchoric acid was most effective. Low temperature did not stop degradation of 14C-ADP in plasma even in the presence of EDTA. 14C-ADP was converted primarily to 14C-AMP. ADPase activity was the same in platelet-rich and platelet-poor plasmas. We conclude that the addition of EDTA and the cooling of plasma did not completely stop the enzymic degradation of ADP.


Root Cortex Provides a Venue for Gas-Space Formation and Is Essential for Plant Adaptation to Waterlogging.
Lysigenous aerenchyma, which develops by death and subsequent lysis of the cortical cells in roots, is essential for internal long-distance oxygen transport from shoot base to root tips of plants in waterlogged soil. Although many studies focus on the amounts of aerenchyma in roots, significance of the size of the root cortex in which aerenchyma forms has received less research attention. In the present study, we evaluated the cross-sectional area of each root tissue in adventitious roots of upland crops, wheat (Triticum aestivum) and maize (Zea mays ssp. mays), and the wetland crop, rice (Oryza sativa) under aerated or stagnant deoxygenated conditions; the latter can mimic the changes in gas composition in waterlogged soils. Our analyses revealed that the areas of whole root and cortex of the three species increased under stagnant conditions. In rice roots, cortex to stele ratio (CSR) and aerenchyma to cortex ratio (ACR), which is associated with the areas of gas spaces, were much higher than those in wheat and maize roots, suggesting that these anatomical features are essential for a high capacity for oxygen transport along roots. To test this hypothesis, rates of radial oxygen loss (ROL), which is the diffusive flux of oxygen from within a root to the external medium, from thick and thin adventitious roots of rice were measured using a cylindrical (root-sleeving) oxygen electrode, for plants with shoots in air and roots in an oxygen-free medium. As expected, the rate of ROL from thick roots, which have larger cortex and aerenchyma areas, was higher than that of thin roots. The rate of ROL was highest at the apical part of rice roots, where aerenchyma was hardly detected, but at which cuboidal cell arrangement in the cortex provides tissue porosity. We conclude that high CSR in combination with large root diameter is a feature which promotes oxygen transport from shoot base to root tips of plants. Moreover, we propose that CSR should be a useful quantitative index for the evaluation and improvement of root traits contributing to tolerance of crops to soil waterlogging.


A new amido-phosphane as ligand for copper and silver complexes. Synthesis, characterization and catalytic application for azide-alkyne cycloaddition in glycerol.
The new sterically hindered amido-phosphane 1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-3,7-diylbis(phenylmethanone), DBPTA (1), has been obtained via an open-cage double N-acylation of 1,3,5-triaza-7-phosphadamantane (PTA) using benzoic anhydride. DBPTA is the only acyl derivative of PTA that contains an aromatic appendage. Due to the bulky nature of the benzoyl C(O)Ph groups, they exhibit mutual anti configuration as confirmed by solution NMR and single crystal X-ray diffraction. Compound 1 is readily soluble in common polar organic and green solvents, making it a very versatile ligand that could be used in a variety of reaction systems. To assess the coordination characteristics of the new phosphane, seven copper complexes of formulas [Cu(DBPTA)4]BF4 (2), [CuX(DBPTA)3] {X = Br (3) and I (4)}, [Cu(μ-X)(DBPTA)2]2 {X = Br (5) and I (6)}, [Cu(bpy)(DBPTA)2]Y {Y = BF4 (7) and BPh4 (8)} {bpy = 2,2'-bipyridine}, and three silver complexes with formulas [Ag(DBPTA)4]NO3 (9), [Ag(Tpm*)(DBPTA)]NO3 (10) and [Ag(Tpms)(DBPTA)] (11) {Tpm* = tris(3,5-dimethyl-1-pyrazolyl)methane, Tpms = tris(pyrazol-1-yl)methanesulfonate} have been synthesised. Compounds 1-11 were characterized by elemental analyses and electrospray ionization mass spectrometry (ESI-MS), as well as by FT-IR and NMR (1H, 13C, 31P, COSY and HSQC) spectroscopic techniques. The catalytic activity of the complexes has been investigated for 1,3-dipolar azide-alkyne cycloaddition reaction using glycerol as a reaction medium to afford 1,4-disubstituted-1,2,3-triazoles. Complex 7 was found to be the most efficient catalyst, affording triazoles in yields up to 97% after 18 h under standard bench experimental conditions (at 23 °C, aerobic conditions and in the absence of any additional bases) and up to 98% after 15 minutes under microwave irradiation (125 °C, 30 W). The catalysis proceeds with a broad substrate scope according to "Click" rules providing a significant contribution to "Green Chemistry".


Attempts to induce interferon production by IdUrd induction and EBV superinfection in human lymphoma lines and their hybrids.
Inducers of the Epstein-Barr virus (EBV) cycle, 5-iodo-2-deoxyuridine (IdUrd), phorbol myristate acetate (TPA) and sodium butyrate were tested for their ability to induce EBV-determined antigens, early antigen (EA) and virus capsid antigen (VCA), and to stimulate interferon (IF) production in a variety of EBV-carrying lymphoid cell lines. IdUrd and TPA induced IF production to various extents in the different lines, whereas sodium butyrate did not. There was no relationship between induction of the EBV cycle and production of IF; the two appear to be independent characteristics. Superinfection with the transforming B95-8 virus substrain of EBV induced IF production, whereas superinfection with the abortively cytopathic, non-transforming P3HR-1 substrain had little or no IF-inducing effect, in spite of its highly potent effect on virus antigen (particularly EA) synthesis. Analysis with specific antisera against IF showed that IF preparations produced by three different lymphoid cell lines in response to IdUrd treatment were composed of a mixture of the Le and F antigenic types, with the latter forming a minor species. In contrast, no detectable F interferon was present in spontaneously produced IF preparations from Namalwa cells, or after induction with B95-8 virus.


Patch Testing for Evaluation of Hypersensitivity to Implanted Metal Devices: A Perspective From the American Contact Dermatitis Society.
The American Contact Dermatitis Society recognizes the interest in the evaluation and management of metal hypersensitivity reactions. Given the paucity of robust evidence with which to guide our practices, we provide reasonable evidence and expert opinion-based guidelines for clinicians with regard to metal hypersensitivity reaction testing and patient management. Routine preoperative evaluation in individuals with no history of adverse cutaneous reactions to metals or history of previous implant-related adverse events is not necessary. Patients with a clear self-reported history of metal reactions should be evaluated by patch testing before device implant. Patch testing is only 1 element in the assessment of causation in those with postimplantation morbidity. Metal exposure from the implanted device can cause sensitization, but a positive metal test does not prove symptom causality. The decision to replace an implanted device must include an assessment of all clinical factors and a thorough risk-benefit analysis by the treating physician(s) and patient.


Modulators of microglia: a patent review.
Microglia are highly dynamic immune cells that play a key role in the development, hemostasis and inflammatory response of the central nervous system. These cells could be a valid therapeutic target because of their involvement in the inflammatory scenario in many neuropathological diseases. Many attempts have aimed to act on microglial cells through different approaches, for instance as viral carriers to transfer genetic material, anti-inflammatory drugs to polarize and shift microglia from M1 toward an M2 phenotype, and stem cell therapy. The challenge remains to find ways to act selectively on this population in the inflammatory site. Original approaches are genetic targeting or pharmacological therapies that exploit some nanomaterials to deliver promising compounds. These results strongly encourage work aimed to modulate activated microglia, laying the base for treating many neurological diseases.


Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia.
Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid β (Aβ) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments.


Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease.
Pramipexole is a clinically effective nonergot dopamine agonist. Pramipexole's receptor interactions differ from ergot agonists in several ways. First, it has high selectivity for interacting with dopamine D2 subfamily receptors (D2, D3, and D4 receptor subtypes) and has little interaction with adrenergic or serotonergic receptors. Second, within the D2 subfamily, it has preferential affinity for the D3 receptor subtype, which, according to preclinical studies, could contribute additional efficacy for treatment of both motor and psychiatric syndromes in Parkinson's disease. Third, it has full intrinsic activity at dopamine D2 subfamily receptors. In addition to pramipexole's unusual receptor profile, whole-animal and cell culture studies suggest that pramipexole might provide neuroprotective effects through depression of dopamine metabolism, antioxidant effects, and stimulation of trophic activity. Pramipexole's demonstrated clinical efficacy for successful treatment in early disease for several years in the absence of L-dopa and as adjunctive therapy with L-dopa in late disease suggests a potential new paradigm for treatment of Parkinson's disease whereby new patients are initiated with pramipexole therapy and L-dopa is added only as necessary.


Selectively Interfering With Intrusive but Not Voluntary Memories of a Trauma Film: Accounting for the Role of Associative Memory.
Intrusive memories of a traumatic event can be reduced by a subsequent interference procedure, seemingly sparing voluntary memory for that event. This selective-interference effect has potential therapeutic benefits (e.g., for emotional disorders) and legal importance (e.g., for witness testimony). However, the measurements of intrusive memory and voluntary memory typically differ in the role of associations between a cue and the emotional memory "hotspots." To test this, we asked participants to watch a traumatic film followed by either an interference procedure (reminder plus Tetris) or control procedure (reminder only). Measurement of intrusions (using a laboratory task) and voluntary memory (recognition for film stills) were crossed with the presence or absence of associative cues. The reminder-plus-Tetris group exhibited fewer intrusions despite comparable recognition memory, replicating the results of prior studies. Note that this selective interference did not appear to depend on associative cues. This involuntary versus voluntary memory dissociation for emotional material further supports separate-trace memory theories and has applied advantages.


Identification and characterization of three Encephalitozoon cuniculi strains.
Microsporidia are increasingly recognized as causing opportunistic infections in immunocompromised individuals. Encephalitozoon cuniculi is probably the most studied mammalian microsporidian that infects insects and mammals, including man. In this study, 8 E. cuniculi isolates were compared and were found to fall into 3 strains. Strain type I includes the rabbit type isolate, as well as isolates from an additional rabbit, a dwarf rabbit, and a mouse. Strain type II includes 2 murine isolates and strain type III includes 2 isolates obtained from domestic dogs. By SDS-PAGE, the 3 strains differ primarily in the molecular weight range of 54-59 kDa where strain type I displays an apparent broad singlet at 57 kDa, strain type II displays an apparent doublet at 54 and 58 kDa, and strain type III displays an apparent broad band at 59 kDa. Antigenic differences were detected in the molecular weight regions of 54-58 kDa as well as 28-40 kDa by Western blot immunodetection using murine antisera raised against E. cuniculi, Encephalitozoon hellem, and the Encephalitozoon-like Septata intestinalis. Polymerase chain reaction (PCR) products containing only small subunit rDNA sequences from the different E. cuniculi isolates formed homoduplexes whereas PCR products containing intergenic rRNA gene sequences formed heteroduplexes in mobility shift analyses. Fok I digestion of the PCR products containing the intergenic rRNA gene region resulted in unique restriction fragment length polymorphism patterns, and DNA sequencing demonstrated that in the intergenic spacer region, the sequence 5'-GTTT-3' was repeated 3 times in strain type I, twice in strain type II, and 4 times in strain type III. This study indicates that there exist at least 3 E. cuniculi strains which may become important in the epidemiology of human E. cuniculi infections. Furthermore, as additional E. cuniculi isolates are characterized, these strains will be named or reclassified once the criteria for taxonomy and phylogenetic tree construction for microsporidia become better defined.


An open-label, phase I study of the polo-like kinase-1 inhibitor, BI 2536, in patients with advanced solid tumors.
This phase I, open-label, dose-escalation study investigated the maximum tolerated dose (MTD) of BI 2536, a small-molecule polo-like kinase (Plk)-1 inhibitor, in two treatment schedules in patients with advanced solid tumors. Secondary objectives included evaluation of safety, efficacy, and pharmacokinetics. Patients received a single i.v. dose of BI 2536 as a 1-hour infusion on days 1 and 8 or a single 24-hour infusion on day 1 of each 21-day treatment course. MTD determination was based on dose-limiting toxicities. Forty-four and 26 patients received each treatment schedule, respectively. The MTD of BI 2536 in the day 1 and 8 schedule was 100 mg per administration (200 mg per course). The MTD for the second dosing schedule was not determined; a 225-mg dose was well tolerated. The most frequently reported treatment-related nonhematologic adverse events were gastrointestinal events and fatigue. Hematotoxicity as the most relevant side effect was similar in both schedules; neutropenia grades 3 and 4 were observed in 16 patients (36.4%) of the day 1 and 8 schedule and 13 patients (50%) of the 24-hour infusion. Fourteen patients (32%) treated in the day 1 and 8 dosing schedule had a best overall response of stable disease. Plasma concentrations of BI 2536 increased dose proportionally, with no relevant accumulation of exposure in the day 1 and 8 dosing schedule. The average terminal half-life was 50 hours. BI 2536 administered in either treatment schedule has adequate safety in patients with advanced solid tumors, warranting further clinical investigation of polo-like kinase-1 inhibitors.


An electrically tunable optical zoom system using two composite liquid crystal lenses with a large zoom ratio.
An electrically tunable-focusing optical zoom system using two composite LC lenses with a large zoom ratio is demonstrated. The optical principle is investigated. To enhance the electrically tunable focusing range of the negative lens power of the LC lens for a large zoom ratio, we adopted two composite LC lenses. Each composite LC lens consists of a sub-LC lens and a planar polymeric lens. The zoom ratio of the optical zooming system reaches ~7.9:1 and the object can be zoomed in or zoomed out continuously at the objective distance of infinity to 10 cm. The potential applications are cell phones, cameras, telescope and pico projectors.


Biomechanical analysis of derotation of the thoracic spine using pedicle screws.
Biomechanical analysis of derotational load-to-failure of pedicle screw (PS) instrumentation in cadaveric thoracic spinal segments. To investigate the derotational torque that can be applied to the thoracic spine through different linked constructs and evaluate the modes of failure. Thoracic derotation with PSs has been shown to provide better 3 plane correction than other methods but the effects of linked PS constructs has not been studied. Four groups of thoracic segments with different PS constructs were loaded to failure with a rotational torque applied to the construct to simulate the left to right derotational force applied to a typical idiopathic dextrorotary thoracic scoliosis curve. Single screw T4 segments instrumented on the medial (group 1M) and lateral (group 1L) sides, bilaterally-linked T5 segments (group 2), unilaterally-linked T6-T9 segments on the medial (group 3M) and lateral (group 3L) sides, and quadrangularly-linked T6-T9 segments (group 4) were loaded with MTS machine in a simulated thoracic derotation model. Single T4 PSs on the medial and lateral sides failed at 4.0 +/- 1.4 Nm (group 1M) and 6.1 +/- 2.5 Nm (group 1L), respectively. Bilaterally-linked T5 screws failed at 11.9 +/- 3.1 Nm (group 2). Unilaterally linked T6-T9 PS constructs on the medial and lateral sides failed at 21.2 +/- 7.5 Nm (group 3M) and 17.9 +/- 11.1 Nm (group 3L), respectively. Quadrangularly-linked PSs failed at 42.5 +/- 14.5 Nm (group 4). CONCLUSION.: A near linear increase in relative torque applied before failure was found with each additional PS linked. Linked constructs allow for significantly greater torque with less risk of PS breach of the spinal canal.


Lumbo-Costo-Vertebral Syndrome with Congenital Lumbar Hernia: Case Report.
Lumbo-costo-vertebral syndrome is a set of rare abnormalities involving vertebral bodies, ribs, and abdominal wall. We present a case of Lumbo-costo-vertebral syndrome in a 6-month old female infant who had a progressive swelling over the right lumbar area since birth. Clinical examination revealed a reducible swelling on the right flank with positive cough impulse. Ultrasonography showed a defect containing bowel loops in the right lumbar region. Chest X-ray revealed scoliosis and hemivertebrae with absent lower ribs on the right side. Computer tomography scan showed hernia sac containing the bowel and the right lobe of the liver with cross fused kidney. Lumbo-costo-vertebraly syndrome is a rare condtion which could be associated with different organ malformations. Simple closure or meshplasty could be done depending on the size of the defect.


Migration of central lines from the superior vena cava to the azygous vein.
To report 11 cases of central venous access catheters migrating from the superior vena cava to the azygos vein in order to raise radiologists' awareness of this possibility. This is a retrospective review of the clinical history and imaging of 11 patients whose central line migrated from the superior vena cava to the azygos vein. The time course of migration, access route of the catheters, outcome, and depth of placement in the superior vena cava were evaluated. All of these catheters were placed from the left; six through the subclavian vein, four as PICC lines, and one from the left internal jugular vein. Seven of the catheters were originally positioned in the superior vena cava. Four of the catheters were originally positioned in the azygos vein and were repositioned into the superior vena cava at the time of placement. The time to migration ranged from 2 to 126 days, average 43 days. In three cases, the migration was not reported at the first opportunity, resulting in a delay in diagnosis ranging from 10 to 27 days. All but one of the catheters extended at least 3.5 cm (range 1.8-7 cm) below the top of the right mainstem bronchus when in the superior vena cava. Risk factors for migration into the azygos vein include placement from a left-sided approach and original positioning in the azygos vein with correction at placement. The depth of placement in the superior vena cava was not a protective factor. It is important to recognize migration because of the elevated risk of complications when central lines are placed in the azygos vein.


Depression and Severity of Glaucoma Among Older Adults in Urban and Suburban Areas.
Depression increases with severity of visual field defect in older adults with primary open-angle glaucoma (POAG). This study aimed to determine the prevalence of depression among patients with POAG and examine the relationship between depression and the severity of POAG in older adults. Three hundred and sixty patients with POAG aged 60 years or above were recruited from 2 tertiary centers located in an urban and suburban area. The participants were stratified according to the severity of their glaucoma based on the scores from the modified Advanced Glaucoma Intervention Study (AGIS) to mild, moderate, severe, and end stage. Face-to-face interviews were performed using the Malay Version Geriatric Depression Scale 14 (mGDS-14) questionnaire. Depression is diagnosed when the score is ≥8. One-way analysis of variance was used to compare the subscores between the groups. Multifactorial analysis of variance was also applied with relevant confounding factors. Depression was detected in 16% of older adults with POAG; a higher percentage of depression was seen in those with end stage disease. There was a significant increase in the mean score of mGDS-14 according to the severity of POAG. There was evidence of an association between depression and severity of visual field defect (P<0.001). There was a significant difference in mGDS-14 score between the pairing of severity of POAG [mild-severe (P=0.003), mild-end stage (P<0.001), moderate-severe (P<0.001), and moderate-end stage (P<0.001)] after adjustment to living conditions, systemic disease, and visual acuity. Ophthalmologists should be aware that older adults with advanced visual field defects in POAG may have depression. The detection of depression is important to ensure adherence and persistence to the treatment of glaucoma.


One patient, two malpositioned hemodialysis catheters, (hepatic vein and ascending lumbar vein), no fluoroscopy.
Cuffed-tunneled hemodialysis catheter (CTHC) application via the femoral vein is a safe and effective alternative when peripheral vascular routes are exhausted for hemodialysis in patients with end-stage renal disease. Also, imaging methods have become more important for the diagnosis or prevention of the possible complications that may develop during or after catheter placements. Here, we present a case of hemodialysis catheter dysfunction due to the insertion of a CTHC tip into the hepatic vein, and into the left ascending lumbar vein at the next attempt. We think that the use of fluoroscopy, whether in the first catheter intervention or catheter change, is extremely important in preventing possible complications that may develop, or detecting them as soon as possible.


Cystic vestibular schwannoma--clinical and experimental studies.
The cystic variant of vestibular schwannoma (VS) presents a therapeutic dilemma. Several studies have previously demonstrated that the surgical outcome in this tumour entity is less favourable than that of solid tumours of comparable size. The "wait and scan" policy has not been recommended for these tumours, as the cystic elements expand, causing displacement of the brainstem and compression of the 4th ventricle, resulting in hydrocephalus. The large tumour size at diagnosis and the cystic contents do not support the role of radiosurgery as a therapeutic option. We have previously published the surgical outcome of 23 cystic VS. The present study includes 44 patients (44 cystic tumours) in a series of 773 tumours (5.7%) who underwent surgery in the period 1976 to 1996. This paper presents the neuroradiological and histological features of the tumours, as well as the results of tumour specimen implantation and surgery in athymic nude mice. Therapeutic options are also discussed.


International and Domestic Students, Perceived Burdensomeness, Belongingness, and Suicidal Ideation.
Suicide is the second leading cause of death for traditional-age college students, and the interpersonal theory of suicide (ITS; Joiner, 2005) provides a cogent framework for predicting which students may be at highest risk. However, little is known about how constructs of ITS operate in cross-cultural contexts. Findings, based on a sample of international and domestic undergraduate students (N = 254), indicated that the ITS construct of perceived burdensomeness was positively associated with suicidal ideation (SI) for both groups. However, campus belongingness emerged as connected with SI for international students, whereas family belongingness emerged as connected with SI for domestic students.


Wine yeasts for the future.
International competition within the wine market, consumer demands for newer styles of wines and increasing concerns about the environmental sustainability of wine production are providing new challenges for innovation in wine fermentation. Within the total production chain, the alcoholic fermentation of grape juice by yeasts is a key process where winemakers can creatively engineer wine character and value through better yeast management and, thereby, strategically tailor wines to a changing market. This review considers the importance of yeast ecology and yeast metabolic reactions in determining wine quality, and then discusses new directions for exploiting yeasts in wine fermentation. It covers criteria for selecting and developing new commercial strains, the possibilities of using yeasts other than those in the genus of Saccharomyces, the prospects for mixed culture fermentations and explores the possibilities for high cell density, continuous fermentations.


Molecular mechanism of Wnt signal pathway in multiple myeloma cell line H929 cell autophagy.
Pathogenic mechanism of multiple myeloma is still unclear yet. Abnormality in cell autophagy is closely correlated with various orthopedic diseases especially multiple myeloma. Therefore, this study investigated the mechanism of cell autophagy abnormality in multiple myeloma occurrence and clinical implications. Using multiple myeloma cell line H929 as the model, cells were treated with UV irradiation. Western blot was used to measure the autophagy of H929 cell, expression level of autophagy molecules and activation of autophagy signal pathway such as Wnt. Using autophagy activator, H929 cell autophagy was potentiated, followed by quantification of autophagy molecular expression and signal pathway such as Wnt activation. Agonist or antagonist of Wnt signal pathway was used to treat H929 cells followed by measuring autophagy molecules and Wnt pathway activation. The correlation between Wnt signal pathway or cell autophagy and occurrence of multiple myeloma was analyzed. UV irradiation treatment on multiple myeloma cell line H929 induced autophagy and Wnt signal pathway activation. The inhibitor of Wnt signal pathway suppressed UV-induced H929 cell autophagy. However, over-expression of Wnt signal pathway enhanced UV-mediated autophagy of H929 cells. The condition of Wnt activation and autophagy level were positively correlated. UV irradiation can induce autophagy of multiple myeloma cells, suggesting that management of cell autophagy might be one possible treatment for multiple myeloma.


During FeS cluster biogenesis, ferredoxin and frataxin use overlapping binding sites on yeast cysteine desulfurase Nfs1.
In mitochondria, cysteine desulfurase (Nfs1) plays a central role in the biosynthesis of iron-sulfur (FeS) clusters, cofactors critical for activity of many cellular proteins. Nfs1 functions both as a sulfur donor for cluster assembly and as a binding platform for other proteins functioning in the process. These include not only the dedicated scaffold protein (Isu1) on which FeS clusters are synthesized but also accessory FeS cluster biogenesis proteins frataxin (Yfh1) and ferredoxin (Yah1). Yfh1 has been shown to activate cysteine desulfurase enzymatic activity, whereas Yah1 supplies electrons for the persulfide reduction. While Yfh1 interaction with Nfs1 is well understood, the Yah1-Nfs1 interaction is not. Here, based on the results of biochemical experiments involving purified WT and variant proteins, we report that in Saccharomyces cerevisiae, Yah1 and Yfh1 share an evolutionary conserved interaction site on Nfs1. Consistent with this notion, Yah1 and Yfh1 can each displace the other from Nfs1 but are inefficient competitors when a variant with an altered interaction site is used. Thus, the binding mode of Yah1 and Yfh1 interacting with Nfs1 in mitochondria of S. cerevisiae resembles the mutually exclusive binding of ferredoxin and frataxin with cysteine desulfurase reported for the bacterial FeS cluster assembly system. Our findings are consistent with the generally accepted scenario that the mitochondrial FeS cluster assembly system was inherited from bacterial ancestors of mitochondria.


Health Conditions: Effect on Function, Health-Related Quality of Life, and Life Satisfaction After Traumatic Spinal Cord Injury. A Prospective Observational Registry Cohort Study.
To analyze relations among injury, demographic, and environmental factors on function, health-related quality of life (HRQoL), and life satisfaction in individuals with traumatic spinal cord injury (SCI). Prospective observational registry cohort study. Specialized acute and rehabilitation SCI centers. Participants (N=340) from the Rick Hansen Spinal Cord Injury Registry (RHSCIR) who were prospectively recruited from 2004 to 2014 were included. The model cohort participants were 79.1% men, with a mean age of 41.6±17.3 years. Of the participants, 34.7% were motor/sensory complete (ASIA Impairment Scale [AIS] grade A). None. Path analysis was used to determine relations among SCI severity (AIS grade and anatomic level [cervical/thoracolumbar]), age at injury, education, number of health conditions, functional independence (FIM motor score), HRQoL (Medical Outcomes Study 36-Item Short-Form Health Survey [Version 2] Physical Component Score [PCS] and Mental Component Score [MCS]), and life satisfaction (Life Satisfaction-11 [LiSat-11]). Model fit was assessed using recommended published indices. Goodness of fit of the model was supported by all indices, indicating the model results closely matched the RHSCIR data. Higher age, higher severity injuries, cervical injuries, and more health conditions negatively affected FIM motor score, whereas employment had a positive effect. Higher age, less education, more severe injuries (AIS grades A-C), and more health conditions negatively correlated with PCS (worse physical health). More health conditions were negatively correlated with a lower MCS (worse mental health), however were positively associated with reduced function. Being married and having higher function positively affected Lisat-11, but more health conditions had a negative effect. Complex interactions and enduring effects of health conditions after SCI have a negative effect on function, HRQoL, and life satisfaction. Modeling relations among these types of concepts will inform clinicians how to positively effect outcomes after SCI (eg, development of screening tools and protocols for managing individuals with traumatic SCI who have multiple health conditions).


Autonomic reflexes in borderline hypertensives.
Autonomic reflexes were studied in 53 patients with borderline hypertension (BLH) and 25 normotensives. BLH patients had higher basal heart rate. With 2 minutes of sustained head-up passive tilt of 50 degrees or 75 degrees, the rise in heart rate was comparable in both groups but the rise in blood pressure was significantly more in the BLH group. The rise in systolic pressure with Valsalva manoeuvre as well as with sustained hand grip was significantly higher in BLH patients. The postural tachycardia index and Valsalva index were significantly lower in BLH patients probably due to higher basal heart rate.


Effect of maternal and paternal line on spatial and temporal marine distribution in Atlantic salmon.
We examined the inheritance of the sea migration pattern of Atlantic salmon, Salmo salar, in a crossing and tagging experiment in the Baltic Sea. Individuals from the parental stocks, Neva and Iijoki, and their reciprocal hybrids were released as 2-year-old smolts, into the same estuary of the Bothnian Sea in 1994. Two thousand smolts from each of the four groups were marked with Carlin tags. The recapture rate of the tags was nearly 10%. We used log-linear models to analyse the marine distribution of the salmon groups from the tag recovery data. The pure stocks and their pooled hybrid groups all showed statistically significant differences between each other in spatial and temporal sea distribution. The Iijoki salmon were more frequently (9%) caught outside the Bothnian Sea than were the Neva salmon (2%). The majority of the Iijoki salmon (55%), but fewer Neva salmon (40%), were caught in the second sea year. In spatial distribution, the hybrids seemed to be intermediate between the parental stocks, with no differences between reciprocal female and male lines. In duration of sea migration and age at maturity, however, the hybrids were very similar to their maternal line, the effect of which was thus clearly stronger than that of the paternal line. Copyright 2000 The Association for the Study of Animal Behaviour.


The validity of anthropometric leg muscle volume estimation across a wide spectrum: from able-bodied adults to individuals with a spinal cord injury.
The assessment of muscle volume, and changes over time, have significant clinical and research-related implications. Methods to assess muscle volume vary from simple and inexpensive to complex and expensive. Therefore this study sought to examine the validity of muscle volume estimated simply by anthropometry compared with the more complex proton magnetic resonance imaging ((1)H-MRI) across a wide spectrum of individuals including those with a spinal cord injury (SCI), a group recognized to exhibit significant muscle atrophy. Accordingly, muscle volume of the thigh and lower leg of eight subjects with a SCI and eight able-bodied subjects (controls) was determined by anthropometry and (1)H-MRI. With either method, muscle volumes were significantly lower in the SCI compared with the controls (P < 0.05) and, using pooled data from both groups, anthropometric measurements of muscle volume were strongly correlated to the values assessed by (1)H-MRI in both the thigh (r(2) = 0.89; P < 0.05) and lower leg (r(2) = 0.98; P < 0.05). However, the anthropometric approach systematically overestimated muscle volume compared with (1)H-MRI in both the thigh (mean bias = 2407cm(3)) and the lower (mean bias = 170 cm(3)) leg. Thus with an appropriate correction for this systemic overestimation, muscle volume estimated from anthropometric measurements is a valid approach and provides acceptable accuracy across a spectrum of adults with normal muscle mass to a SCI and severe muscle atrophy. In practical terms this study provides the formulas that add validity to the already simple and inexpensive anthropometric approach to assess muscle volume in clinical and research settings.


The effect of inter-implant distance on retention and resistance to dislodging forces for mandibular implant-tissue-supported overdentures.
The effect of inter-implant distance on retention and resistance of implant-tissue-supported overdentures is lacking in the literature. An in vitro study was performed to evaluate this effect for mandibular implant-tissue-supported overdentures retained by two ball attachments. An acrylic cast of an edentulous mandible was fabricated. Three pairs of implants were symmetrically placed at both sides of the midline. The inter-implant distance was 10, 25, and 35 millimeters in positions A, B and C, respectively. A framework simulating the overdenture was fabricated on the cast. Six attachment housings were placed within the overdenture. For each sample, two ball abutments were screwed onto the implant pairs and two pink nylon inserts were seated in their respective attachment housings. The samples were tested in three groups of 15 (A, B, and C). The testing machine applied tensile dislodging forces and peak loads were measured in three directions: vertical, oblique, and anterior-posterior. A one-way ANOVA followed by Tukey's HSD was used to determine groups that were significantly different. Tests were carried out at 0.05 level of significance. Peak loads for the anterior-posteriorly directed dislodging forces were significantly the highest for group C (P<0.05); 21.25 N±3.05 N, while there were no statistically significant differences among groups with vertically and obliquely directed forces (P>0.05). Inter-implant distance did not affect the vertical retention and oblique resistance of mandibular implant-tissue-supported overdentures; however, it affected anterior-posterior resistance.


Single-incision laparoscopic cholecystectomy: is it more than a challenge?
Single-incision laparoscopic surgery (SILS) is a promising technique with regard to reducing postoperative pain, decreasing complications, and improving cosmesis. Between September 2008 and April 2009, 20 patients underwent cholecystectomy via SILS. The umblicus was the access point of entry to the abdomen for all the patients. Of the 20 cholecystectomies, 19 were performed with SILS. Failure of trocar insertion was the reason for conversion with the first patient. No complications or mortalities were associated with the technique. The mean operating time was 94 min. The use of SILS for cholecystectomy is safe and feasible with reasonable operation times.


Effects of outpatient treatment for problem drinkers.
This study was designed to investigate the effects of treatment length restriction and follow-up interview style on the outcomes of male alcohol abusers in out-patient treatment. Subjects (N = 48) were randomly assigned to one of four independent groups based on the factorial combination of the two independent variables. Extensive pretreatment data were collected about subjects' drinking and related behaviors, and subjects were then scheduled for monthly interviews. Subjects were interviewed for 18 months postadmission concerning these same factors. Subjects' self-reports were compared with collateral reports, official records, and breath tests. Outcome results showed no effects of follow-up interview style or treatment length restriction on drinking behavior and employment outcomes. However, subjects' drinking behavior postadmission was considerably improved compared to their pretreatment ethanol consumption. Temporal analyses of the drinking behavior data showed that it was possible to predict drinking behavior, especially of the same type, within pretreatment and postadmission intervals. However, it was not possible to predict postadmission drinking from pretreatment drinking. Treatment implications of the findings are discussed.


Engineering of the extracellular matrix: working toward neural stem cell programming and neurorestoration--concept and progress report.
In the concept of neurorestoration, cellular and structural elements that have been lost are replaced, and their function is restored. Central to this therapeutic strategy is the transplantation of neural progenitor cells such as clonogenically expanded stem cells. Stem cells make decisions regarding fate and patterning in response to external environmental signals. The therapeutic effectiveness of neural stem cells may be facilitated by the ability to manipulate these signals in a temporal and spatially appropriate fashion. Artificial deoxyribonucleic acid and artificial protein technology combines elements of protein engineering, molecular biology, and recombinant deoxyribonucleic acid technology to produce proteins with functional domains derived from naturally occurring proteins and represents a potentially powerful tool to modulate stem cell behavior. To this end, we have developed three artificial extracellular matrix proteins that incorporate the active domain of hJagged1 and hDelta1 into an elastin backbone. hJagged1 and hDelta1 are members of the DSL family of ligands to the Notch receptor, a signaling system that is very important in development and is the strongest known signal to instruct neural progenitor cells to choose glial fates over neuronal fates. The successful cloning of the artificial genes was confirmed by test digestions with appropriate restriction enzymes as well as direct deoxyribonucleic acid sequencing. In addition, we have demonstrated that all three artificial extracellular matrix proteins express at a high level in a prokaryotic host. This report describes the concept and progress in an entirely novel and previously unreported approach to modulate neural stem cell behavior. Its future application could include in vitro processing of stem cells before transplantation, supporting and programming the cells after transplantation, as well as the development of bioactive biomaterials.


Procedural bleeding risk, rather than conventional coagulation tests, predicts procedure related bleeding in cirrhosis.
Standard coagulation parameters are used to guide prophylactic blood product transfusion prior to invasive procedures in cirrhotic patients despite limited high-quality evidence. We aimed to describe coagulation parameters and prophylactic blood product use in cirrhotic patients having invasive procedures, and the influence of both on periprocedural bleeding. We conducted a cohort study of cirrhotic patients undergoing invasive procedures at a referral hospital. Procedures were classified into low or moderate-high bleeding risk. Prophylactic blood component was defined as fresh frozen plasma, cryoprecipitate or platelet transfusion prior to procedures. Univariate and multivariate logistic regression was performed to identify factors associated with procedure-related bleeding. We identified 566 procedures in 233 cirrhotic patients. Prophylactic blood product was given before 16% of high-risk and 11% of low-risk procedures (P = 0.18). Eight (8.3%) high-risk procedures were complicated by postprocedural bleeding, six of which occurred in patients without significant coagulopathy. The bleeding rate for low-risk procedures was 0.4%. For patients with international normalized ratio >1.5, platelet count <50 x 109/L, or both, the rate of bleeding was comparable between those given and not given prophylactic blood products (3.1 vs. 1.9%; P = 0.63). After adjusting for age, sex, platelet count, international normalized ratio, acute kidney injury, sepsis and model of end-stage liver disease, the only factor significantly predicting procedure-related bleeding was the procedural bleeding risk category (P < 0.01). Procedure-related bleeding in cirrhotic patients cannot be accurately predicted by INR or platelet count, nor prevented by blood component prophylaxis using these parameters. Procedure-related bleeding is best predicted by the bleeding risk status of procedures.


Phenotypic landscape inference reveals multiple evolutionary paths to C4 photosynthesis.
C4 photosynthesis has independently evolved from the ancestral C3 pathway in at least 60 plant lineages, but, as with other complex traits, how it evolved is unclear. Here we show that the polyphyletic appearance of C4 photosynthesis is associated with diverse and flexible evolutionary paths that group into four major trajectories. We conducted a meta-analysis of 18 lineages containing species that use C3, C4, or intermediate C3-C4 forms of photosynthesis to parameterise a 16-dimensional phenotypic landscape. We then developed and experimentally verified a novel Bayesian approach based on a hidden Markov model that predicts how the C4 phenotype evolved. The alternative evolutionary histories underlying the appearance of C4 photosynthesis were determined by ancestral lineage and initial phenotypic alterations unrelated to photosynthesis. We conclude that the order of C4 trait acquisition is flexible and driven by non-photosynthetic drivers. This flexibility will have facilitated the convergent evolution of this complex trait. DOI:http://dx.doi.org/10.7554/eLife.00961.001.


Campylobacter fetus subspecies fetus bacteremia associated with chorioamnionitis and intact fetal membranes.
Campylobacter fetus subspecies fetus was isolated from the blood of a patient with chorioamnionitis and intact fetal membranes. The mother improved after appropriate antibiotic treatment, but the infant died of neonatal infection a few minutes after delivery. This is a very unusual etiology of intra-amniotic infection.


Prevalence, predictors and prognosis of patients with heart failure requiring nursing care.
Although the need for nursing care (NC) in heart failure (HF) patients is recognized, detailed information on the current status in Japan is lacking. METHODS AND RESULTS: In the CHART-2 Study, we obtained information on daily life, physical ability, nutrition and mental status for 4,174 patients (mean age, 67.1±10.8 years; 73.3% male) out of 10,219 patients. We examined the prevalence, baseline characteristics and clinical outcomes of stage B and C/D HF patients requiring NC. The prevalence of HF requiring NC was significantly higher in stage C/D (38.6%) than in stage B (30.4%; P<0.001). Among the reasons for requiring NC, physical dysfunction was most prevalent in both stage B (20.6%) and C/D (29.0%). Compared with the non-NC group, the NC group was characterized by higher age, higher prevalence of female gender and cerebrovascular disease, and increased plasma brain natriuretic peptide regardless of HF stage. During a median follow-up of 12.7 months after the survey, the NC group had a significantly higher mortality compared with the non-NC group (9.6% vs. 3.6%, P<0.001). On multivariate logistic analysis depressive mental status (hazard ratio [HR], 3.61; P<0.001) and dementia (HR, 2.70; P<0.001) were significantly associated with NC need. In HF patients, NC need is considerably high and is associated with increased mortality regardless of HF stage in Japan.


Self-Help for Depression via E-mail: A Randomised Controlled Trial of Effects on Depression and Self-Help Behaviour.
Self-help or self-management strategies are commonly used to deal with depression, but not all are thought to be helpful. A previous study found that sub-threshold depression symptoms were improved by an e-mail intervention that encouraged the use of evidence-based self-help strategies. To investigate whether these e-mails were effective for adults with a range of depression symptomatology including major depression. The study was a parallel-group randomised controlled trial. Adult participants with any level of depressive symptoms were recruited over the internet from the United Kingdom, Australia, Canada, Ireland, New Zealand and the United States. Participants were randomised to receive a series of e-mails either promoting the use of evidence-based self-help strategies or containing depression information as a control. E-mails were sent automatically twice a week for six weeks. Depression symptoms were assessed with the self-rated Patient Health Questionnaire depression scale (PHQ-9). 1736 participants with a wide range of symptom severity were recruited and assigned to active (n = 862) and control (n = 874) groups. However, there was a significant attrition rate, with 66.9% lost to follow-up at post-intervention. Both groups showed large improvements in depression symptoms overall, with no significant difference in improvement at the end of the study (mean difference in improvement 0.35 points, 95% CI: -0.57 to 1.28, d = 0.11, 95% CI: -0.06 to 0.27), although there was a small effect at the study mid-point. Results were similar for the sub-group of participants with major depression. The active group showed small to moderate improvements in self-help behaviour (d = 0.40, 95% CI: 0.23 to 0.56). These results suggest that the e-mails were able to increase participants' use of evidence-based self-help, but that this did not improve depression more than an attention control. NCT01399502.


Distracted and down: neural mechanisms of affective interference in subclinical depression.
Previous studies have shown that depressed individuals have difficulty directing attention away from negative distractors, a phenomenon known as affective interference. However, findings are mixed regarding the neural mechanisms and network dynamics of affective interference. The present study addressed these issues by comparing neural activation during emotion-word and color-word Stroop tasks in participants with varying levels of (primarily subclinical) depression. Depressive symptoms predicted increased activation to negative distractors in areas of dorsal anterior cingulate cortex (dACC) and posterior cingulate cortex (PCC), regions implicated in cognitive control and internally directed attention, respectively. Increased dACC activity was also observed in the group-average response to incongruent distractors, suggesting that dACC activity during affective interference is related to overtaxed cognitive control. In contrast, regions of PCC were deactivated across the group in response to incongruent distractors, suggesting that PCC activity during affective interference represents task-independent processing. A psychophysiological interaction emerged in which higher depression predicted more positively correlated activity between dACC and PCC during affective interference, i.e. greater connectivity between cognitive control and internal-attention systems. These findings suggest that, when individuals high in depression are confronted by negative material, increased attention to internal thoughts and difficulty shifting resources to the external world interfere with goal-directed behavior.


Steatosis regression assessed by cap after Vitamin 'D' supplementation in NAFLD patients with Vitamin 'D' deficiency.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and previous studies suggested a relationship between vitamin D deficiency and NAFLD. It is suggested that vitamin D supplementation may have significant beneficial effect on liver biochemistry and histology. This study aims to assess the degree of possible steatosis regression using controlled attenuation parameter (CAP) in NAFLD patients with vitamin D deficiency after vitamin D supplementation and evaluating its effect on lipid profile and transaminases. This study was conducted on 100 NAFLD patients with vitamin D deficiency. They received 10000 IU/week of vitamin D orally for 3 months. CAP was used to assess hepatic steatosis and fibrosis before/after intervention. Transaminases, lipid profile, and vitamin D levels were evaluated before/after treatment. Serum AST, ALT, cholesterol, TG, LDL and HDL showed a significant reduction posttreatment in patients with both normal and elevated baseline levels ( P < 0.001). The posttreatment mean CAP showed a significant reduction (300.44 ± 37.56 vs. 265 ± 36.19 dB/ml) ( P < 0.001), and there was a significant improvement in the mean fibrosis values by LSM (5.32 ± 1.53 vs. 4.86 ± 1.28 KPa) ( P = 0.001). After supplementation, serum vitamin D level was raised significantly in the majority of patients ( P < 0.001); however, only 13% of them reached sufficient levels (>30 ng/ml), insufficient levels (20-29 ng/ml) was reached in 83% and 5% showed vitamin D deficiency (<20 ng/ml). A significant improvement was detected in hepatic steatosis (by CAP); mean values of LSM, transaminases and lipid profile after three months of oral vitamin D supplementation.


Thermoseed hyperthermia treatment of mammary orthotopic transplantation tumors in rats and impact on immune function.
To evaluate the effect of thermoseed inductive heating on mammary orthotopic transplantation tumors and immunologic function in rats. Walker-256 tumor cells were inoculated subcutaneously into the mammary glands of Wistar rats. Rats were allocated to five treatment groups as follows: i) C group (control group); ii) M group (magnetic field group); iii) T group (thermoseed control group); iv) H1 group (hyperthermia treatment, 45 degrees C for 30 min); v) H2 group (hyperthermia treatment, 50-55 degrees C for 10 min). Immediately, 12 and 24 h after hyperthermia, two rats were sacrificed in each group for pathological and immunohistochemical examination of the expression of PCNA and HSP70. Tumor volume was measured and long-term survival was observed. The T lymphocyte subgroup IL-2 and IFN-gamma levels were measured in C, H1 and H2 groups. Both types of hyperthermia induced necrosis and apoptosis in the tumor tissue, decreased tumor volume (P<0.05), and increased survival time (P<0.01). The expression of PCNA and HSP70 in hyperthermia group was significantly different compared to the C, M and T groups (P<0.05), Hyperthermia increased CD4+ T lymphocytes and the levels of IL-2 and IFN-gamma (P<0.05). Both types of hyperthermia can suppress the growth of mammary tumors and improve immunological function of rats.


MAPK and JAK-STAT pathways dysregulation in plasmablastic lymphoma.
Plasmablastic lymphoma (PBL) is an aggressive B-cell lymphoma with an immunoblastic/large-cell morphology and terminal B-cell differentiation. The differential diagnosis from Burkitt lymphoma, plasma cell myeloma and some variants of diffuse large B-cell lymphoma may be challenging because of the overlapping morphological, genetic and immunophenotypic features. Furthermore, the genomic landscape in PBL is not well known. To characterize the genetic and molecular heterogeneity of these tumors, we investigated 34 cases of PBL using an integrated approach, including fluorescence in situ hybridization, targeted sequencing of 94 B-cell lymphoma-related genes, and copy-number arrays. PBL were characterized by high genetic complexity including MYC translocations (87%), gains of 1q21.1-q44, trisomy 7, 8q23.2- q24.21, 11p13-p11.2, 11q14.2-q25, 12p and 19p13.3-p13.13, losses of 1p33, 1p31.1-p22.3, 13q and 17p13.3-p11.2, and recurrent mutations of STAT3 (37%), NRAS and TP53 (33%), MYC and EP300 (19%) and CARD11, SOCS1 and TET2 (11%). Pathway enrichment analysis suggested a cooperative action between MYC alterations and MAPK (49%) and JAK-STAT (40%) signaling pathways. Of note, Epstein-Barr virus (EBV)-negative PBL cases had higher mutational and copy-number load and more frequent TP53, CARD11 and MYC mutations, whereas EBV-positive PBL tended to have more mutations affecting the JAK-STAT pathway. In conclusion, these findings further unravel the distinctive molecular heterogeneity of PBL identifying novel molecular targets and the different genetic profile of these tumors in relation to EBV infection.


[The mortality of the able-bodied population in the Irkutsk oblast].
The comprehensive evaluation of the irrevocable demographic losses among the able-bodied population in Irkutsk oblast. The quantitative structural analysis was implemented as applied to the characteristics of mortality of this population contingent. The peculiarities of formation of the vital potential of the economically active population. The structure and hierarchy of factors conditioning the worst losses of vital potential


Association between physician adoption of a new oral anti-diabetic medication and Medicare and Medicaid drug spending.
In the United States, there is well-documented regional variation in prescription drug spending. However, the specific role of physician adoption of brand name drugs on the variation in patient-level prescription drug spending is still being investigated across a multitude of drug classes. Our study aims to add to the literature by determining the association between physician adoption of a first-in-class anti-diabetic (AD) drug, sitagliptin, and AD drug spending in the Medicare and Medicaid populations in Pennsylvania. We obtained physician-level data from QuintilesIMS Xponent™ database for Pennsylvania and constructed county-level measures of time to adoption and share of physicians adopting sitagliptin in its first year post-introduction. We additionally measured total AD drug spending for all Medicare fee-for-service and Part D enrollees (N = 125,264) and all Medicaid (N = 50,836) enrollees with type II diabetes in Pennsylvania for 2011. Finite mixture model regression, adjusting for patient socio-demographic/clinical characteristics, was used to examine the association between physician adoption of sitagliptin and AD drug spending. Physician adoption of sitagliptin varied from 44 to 99% across the state's 67 counties. Average per capita AD spending was $1340 (SD $1764) in Medicare and $1291 (SD $1881) in Medicaid. A 10% increase in the share of physicians adopting sitagliptin in a county was associated with a 3.5% (95% CI: 2.0-4.9) and 5.3% (95% CI: 0.3-10.3) increase in drug spending for the Medicare and Medicaid populations, respectively. In a medication market with many choices, county-level adoption of sitagliptin was positively associated with AD spending in Medicare and Medicaid, two programs with different approaches to formulary management.


High-speed, inline measurement of protein activity and inactivation processes by supercontinuum attenuation spectroscopy.
Some proteins such as catalase and glutamate dehydrogenase (GDH) are very sensitive to external factors such as irradiation or heat, which may cause inactivation. Since proteins are used in a wide field of applications, the entire activity has to be ensured during the whole process. By default, activity is measured by invasive and offline activity assays. To avoid the need for a time-consuming offline analysis, we developed an optical high-speed measurement technique, which may form the basis for the non-invasive inline control of enzyme processes e.g. in the textile or food industry. The technique is based on attenuation spectroscopy using a supercontinuum laser source in combination with multivariate data analysis, in particular partial least squares regression (PLSR). For verification of the approach, samples treated by various stresses were analyzed in parallel by activity assays and our new method. Applying this technique, we were able to determine the activity in the turbid catalase samples after heat treatment, addition of guanidine-HCl or irradiation with UV light by applying partial least squares regression. Furthermore, we demonstrate that the combination of broadband attenuation spectroscopy and PLSR enables us to determine also the activity of GDH in clear solutions after heat treatment.