Riboflavin/UVA photochemical therapy for severe infectious keratitis.
To describe the antibacterial activity of treatment with riboflavin and ultraviolet A light (UVA) in cases of severe infectious keratitis. A retrospective analysis was performed of an interventional case series in which 6 eyes of 6 patients with severe infectious keratitis, all of whom were refractive to multidrug conventional therapy, were treated with riboflavin/UVA. The procedure was conducted according to the standardized protocol of corneal collagen crosslinking (CXL) for keratoconus. Best spectacle-corrected visual acuity and clinical outcomes were evaluated before and during the follow-up period. Five of the 6 patients showed rapid reduction in symptoms and decreased infiltrate size after riboflavin/UVA photochemical therapy. Signs of infection and inflammation mostly resolved within 1 to 2 weeks after the treatment. Despite this therapy, one patient continued to deteriorate, and penetrating keratoplasty was performed. The adjunctive use of riboflavin/UVA photochemical therapy has a positive effect on refractory infectious keratitis. The treatment seems to be safe and effective and should be considered as part of the first-line therapy in severe cases of infectious keratitis.


Nocardioides malaquae sp. nov., a novel actinobacterium isolated from sewage sludge of a fisheries processing factory.
A Gram-stain-positive, rod-shaped, strictly aerobic bacterial strain (Y6T) was isolated from a sewage sludge sample collected from a fisheries processing factory in Zhoushan, Zhejiang Province, PR China. The growth range of NaCl concentration was 0-6.0 % (w/v), with an optimum at 3.0 % (w/v). The temperature range for growth was 10-42 °C, with an optimum at 37 °C. The pH range for growth was pH 7.0-10.0, with an optimum at pH 9.0. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Y6T belonged to the genus Nocardioides and showed the highest sequence similarity of 97.8 % to Nocardioides jishulii dk3136T. The average nucleotide identity and in silico DNA-DNA hybridization values between strain Y6T and the reference strains were 76.9-81.2 % and 20.6-23.6 %, respectively. Chemotaxonomic analysis indicated that the sole respiratory quinone was MK-8(H4) and the predominant cellular fatty acids were iso-C16 : 0, 10-methyl-C17 : 0 and C18 : 1 ω9c. The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, four unidentified phospholipids, three unidentified aminolipids and five unidentified lipids. The peptidoglycan was ll-2,6-diaminopimelic acid. On the basis of the phenotypic, genotypic, phylogenetic and chemotaxonomic features, strain Y6T is considered to represent a novel species, for which the name Nocardioides malaquae sp. nov. is proposed. The type strain is Y6T (=KCTC 49504T=MCCC 1K04765T).


HEART and TIMI Scores Predict Severe Coronary Atherosclerosis in Patients With End-Stage Renal Disease.
Objectives History, EKG, age, risk factors, and troponin (HEART) and thrombolysis in myocardial infarction (TIMI) risk calculators have been validated to predict the risk of subsequent acute coronary syndromes and in some studies, severe coronary atherosclerosis in patients with a concerning clinical history. Their performance in patients with end-stage renal disease (ESRD), a population with a high pretest probability for the condition, is unknown. We aimed to determine whether HEART and TIMI scores can predict severe coronary atherosclerosis in patients with end-stage renal disease (ESRD). Methods A single-center retrospective cohort of admitted patients aged 18 years or older with ESRD on dialysis who underwent coronary angiography during admission (November 2010 to December 2017) was retrospectively reviewed. The outcome of coronary angiography was compared with the calculated HEART and TIMI scores at the time of presentation. Receiver operating characteristics and logistic regression models were used to determine optimal score cutoffs, score usefulness, and associations between outcomes, scores, and patient characteristics. Results Among 231 patient encounters, the mean HEART and TIMI scores were 6±2 and 3±1 points, respectively. Patients with diabetes mellitus, those 65 years old and older, and those reported to have angina pectoris were more likely to show severe coronary artery disease (CAD) lesions. Optimal score cutoffs for determining severe coronary lesions were between six and seven (area under the curve (AUC)=0.754, confidence interval (CI): 0.682-0.826) and between three and four (AUC=0.716, CI: 0.640-0.792) for the HEART and TIMI scores, respectively. Conclusion Similar to the general population, HEART and TIMI scores can predict severe coronary atherosclerosis in the complex ESRD population.


Pharmacokinetics of ibafloxacin following intravenous and oral administration to healthy Beagle dogs.
The pharmacokinetics of ibafloxacin, a new veterinary fluoroquinolone antimicrobial agent, was studied following intravenous (i.v.) and oral administration to healthy dogs. The mean absolute bioavailability of ibafloxacin after oral doses of 7.5, 15 and 30 mg/kg ranged from 69 to 81%, indicating that ibafloxacin was well absorbed by dogs. Ibafloxacin was also absorbed rapidly [time of maximum concentration (t(max)) 1.5 h], reaching a mean maximum concentration (C(max)) of 6 microg/mL at 15 mg/kg, well distributed in the body [large volume of distribution at steady state (V(ss)) and V(area) of 1.1 L/kg and 4 L/kg, respectively], and exhibited an elimination half-life of 5.2 h and a low total body clearance (8.7 mL/min/kg). Both C(max) and area under the concentration-time curve (AUC) showed dose proportionality over the dose range tested (7.5-30 mg/kg). The pharmacokinetics of ibafloxacin was similar following single and repeated dosage regimens, implying no significant accumulation in plasma. Food promoted the absorption of ibafloxacin by increasing C(max) and AUC, but did not change t(max). High amounts of the metabolites, mainly 8-hydroxy- and, 7-hydroxy-ibafloxacin were excreted in urine and faeces, either unchanged or as glucuronide conjugates. Following oral administration of 15 mg ibafloxacin/kg, the total recovery of ibafloxacin, its metabolites and conjugates in urine and faeces was 61.9-99.9% of the dose within 48 h.


Psychopathology and developmental delay in homeless children: a pilot study.
The authors report a survey of 50 parent-child pairs from homeless families housed in New York City hotels. The purpose of the survey was to determine the extent of emotional or behavioral disturbances and of developmental delays in homeless children aged 4 through 10 years, the presence of depression or a history of depression or other psychiatric problems in the parents of these children, and to determine whether the children and adults had mental health needs. The results indicate that nearly all of the children showed some difficulties. Sixty-one percent of the children had receptive verbal functioning at or below the first percentile for age, 29% were functioning at the fifth percentile for age in psychomotor ability, and 38% exhibited emotional and behavioral problems. Twenty-eight percent of the parents exhibited evidence of mild to severe depression; a smaller percentage admitted to past psychiatric problems.


Lung transplant waitlist mortality: height as a predictor of poor outcomes.
The LAS was designed to minimize pretransplant mortality while maximizing post-transplant outcome. Recipients <12 are not allocated lungs based on LAS. Waitlist mortality has decreased for those >12, but not <12, suggesting this population may be disadvantaged. To identify predictors of waitlist mortality, a retrospective analysis of the UNOS database was performed since implementation of the LAS. There were 16,973 patients listed for lung transplant in the United States; 12,070 (71.1%) were transplanted, and 2498 (14.7%) patients died or were removed from the wait list. Significantly more pediatric patients died or were removed compared with adults (22.0% vs. 14.4%, p < 0.01). In multivariate analysis, in addition to higher LAS at time of listing (adj. HR1.058, 1.055-1.060), shorter height (1.008, 1.006-1.010), male gender (1.210, 1.110-1.319), and requiring ECMO (1.613, 1.202-2.163) were associated with pretransplant mortality. Post-transplant survival was not affected by height. The current age cutoff may impose limitations within the current lung allocation system in the United States. Height is an independent predictor of waitlist mortality and may be a valuable factor for the development of a comprehensive lung allocation system.


Quantitative trait loci associated with resistance to Fusarium head blight and kernel discoloration in barley.
Resistance to Fusarium head blight (FHB), deoxynivalenol (DON) accumulation, and kernel discoloration (KD) in barley are difficult traits to introgress into elite varieties because current screening methods are laborious and disease levels are strongly influenced by environment. To improve breeding strategies directed toward enhancing these traits, we identified genomic regions containing quantitative trait loci (QTLs) associated with resistance to FHB, DON accumulation, and KD in a breeding population of F(4:7) lines using restriction fragment length polymorphic (RFLP) markers. We evaluated 101 F(4:7) lines, derived from a cross between the cultivar Chevron and an elite breeding line, M69, for each of the traits in three or four environments. We used 94 previously mapped RFLP markers to create a linkage map. Using composite interval mapping, we identified 10, 11, and 4 QTLs associated with resistance to FHB, DON accumulation, and KD, respectively. Markers flanking these QTLs should be useful for introgressing resistance to FHB, DON accumulation, and KD into elite barley cultivars.


Coordination chemistry of platinum and palladium in the solid-state: synthesis of imidazole and pyrazole complexes.
Solid-state reactions of palladium(II) and platinum(II) chloride complexes with imidazole (Him) and pyrazole (Hpz) or their hydrochloride salts are shown to produce metal complex salts and coordination compounds. Thus, K(2)[MCl(4)] or MCl(2) can be ground with imidazolium chloride ([H(2)im]Cl) to produce the salts [H(2)im](2)[MCl(4)] (M = Pd, 1; Pt, 5), which can then be dehydrochlorinated in the solid state to produce the coordination compounds trans-[PdCl(2)(Him)(2)] 3 or cis-[PtCl(2)(Him)(2)] 6. The complex cis-[PdCl(2)(Him)(2)] 2 is produced when Pd(OAc)(2) is ground with [H(2)im]Cl. Reaction of platinum chloride reagents with imidazole (Him) also produces cis-[PtCl(2)(Him)(2)] 6, but reaction of imidazole with analogous palladium chloride reagents first produces [Pd(Him)(4)]Cl(2) 4 which then slowly converts to trans-[PdCl(2)(Him)(2)] 3. Grinding pyrazolium chloride with K(2)[MCl(4)] produces [H(2)pz](2)[MCl(4)] (M = Pd, 7; Pt, 10), which may also be dehydrochlorinated in the solid state to produce the coordination compounds trans-[PdCl(2)(Hpz)(2)] 8 or cis-[PtCl(2)(Hpz)(2)] 11. Grinding K(2)[PdCl(4)] or PdCl(2) with pyrazole gives [Pd(Hpz)(4)]Cl(2) 9, which is then slowly converted into trans-[PdCl(2)(Hpz)(2)] 8. Grinding PtCl(2) with Hpz generates [Pt(Hpz)(4)]Cl(2) 12, but using K(2)PtCl(4) as the metal source does not generate the same product. The single-crystal structures of 8, a new polymorph of 11 and [H(2)pz](2)[PtCl(6)].2H(2)O (isolated as a decomposition product) are reported for the first time, and the structures of 5 and 10 have been solved ab ibitio from XRPD data.


Attitude and Participation of Men Regarding Prenatal Care, Childbirth, and Postpartum Care in Kashan City, Iran.
Men's involvement in perinatal care has benefits including reduced preterm childbirth, and better development of children. This study was conducted with the aim to determine the attitude and participation of men in prenatal, childbirth, and postpartum care. This cross-sectional study was performed on 280 men in industrial units in Kashan city, Iran (November 2014-March 2015). The participants were selected using cluster sampling method. They completed a researcher-made three-part questionnaire. The data were analyzed using independent-samples t test and analysis of variance (ANOVA). The mean (SD) score of men's attitude and practice regarding perinatal care were 40.12 (5.00) and 61.65 (6.87), respectively. A significant difference was observed between the practice of men with different education levels (F2,75 = 3.63, p = 0.001). The participation of men in perinatal care was low. It is recommended that healthcare providers make visits in the presence of husbands and simultaneously provide training for the couples during the perinatal period.


False positive 18F-FDG PET scan in adrenal oncocytoma.
18F-FDG whole-body positron emulsion tomography (18F-FDG PET) has become an established imaging modality for a variety of cancers. Today, 18F-FDG PET is utilized to differentiate benign from malignant non-functioning adrenal masses. In this report, a 25-year-old woman presented with a 2-month history of left flank pain. Abdominal CT revealed a left 6.5 x 4.5 cm adrenal mass with regular margins and focal calcification. To make a differential diagnosis, 18F-FDG PET was performed. Preoperative laboratory studies showed that the mass was non-functioning. A left adrenalectomy was performed through a left subcostal incision. The final pathologic evaluation revealed adrenal oncocytoma. We present the disassociation between preoperative 18F-FDG PET and pathologic findings of a benign adrenocortical oncocytoma.


May-Thurner Syndrome, an Often Overlooked Cause of Deep Vein Thrombosis: A Case Report.
Deep vein thrombosis (DVT) is a common medical condition, but the predisposing anatomical factors, which may be amenable to definitive treatment, are usually overlooked. Therefore, a high index of clinical suspicion is the key to early diagnosis. We report here one such case of May-Thurner syndrome (MTS) to raise awareness. MTS (also known as iliac vein compression syndrome) should be suspected in cases of extensive DVT of the leg, particularly involving the iliac vein on the left side. The prognosis is improved with thrombolysis followed by angioplasty and stent to address the venous stenosis.


Modified indirect immunodetection allows study of murine tissue with mouse monoclonal antibodies.
The indirect immunodetection method is powerful in detecting antigens in situ, but to date mouse monoclonal antibodies (MAbs) could not be used in immunohistochemical studies of murine tissues without severe background staining. We report here a modification of this method in which mouse MAbs are used to detect murine antigens in cryosections. Before application to the section, mouse MAbs and conjugated anti-mouse antiserum were allowed to complex in vitro. After blocking of the unbound secondary antiserum with normal mouse serum, standard immunohistochemistry was performed. Fifty percent of a randomly chosen panel of over 40 mouse MAbs recognized their antigens in our model system. Adaptation of, for example, the fixation protocol can probably even increase this number. An MAb to the intermediate filament protein desmin, staining both smooth and striated muscle, was used to demonstrate this technique in cryosections of 15-day-old mouse embryos. In contrast to standard immunohistochemistry with the same antibodies under the same conditions, background staining was completely absent with this technique. With this modification to the well-established indirect detection method, the usefulness of mouse MAbs is significantly increased.


A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies.
A highly sensitive immunoenzymatic technic is presented. The method involves three sequential steps: (1) primary antibody, (2) biotin-labeled secondary antibody, and (3) avidin-biotin-peroxidase complex. Avidin, an egg white protein, has four binding sites for the low-molecular-weight vitamin biotin. Many moieties of biotin can be coupled to the peroxidase molecule. Thus, since a relatively large amount of avidin is incubated with biotin-labeled peroxidase, avidin serves as a link between biotin-peroxidase molecules; in turn, biotin-peroxidase serves as a link between avidin molecules. Consequently, this large lattice-like complex with biotin-binding capability can be attracted to the sites of biotin-labeled antibody, producing a superior staining sensitivity. Several commercially available radioimmunoassay antibodies (e.g., antiglucagon, prolactin, gastrin, growth hormone, and thyroid-stimulating hormone antibodies) were tested for immunohistochemical staining. The unlabeled antibody peroxidase-antiperoxidase method fails to stain gastrin or thyroid-stimulating secretory cells when using these antibodies, and a relatively high antibody concentration is required to produce a positive reaction for glucagon, prolactin, and growth hormone. In contrast, the avidin-biotin-peroxidase complex method successfully demonstrates polypeptide hormones even when antibodies are diluted 20 to 40 times.


Cobalt induces hypoxia-inducible factor-1alpha expression in airway smooth muscle cells by a reactive oxygen species- and PI3K-dependent mechanism.
Cobalt can mimic hypoxia and has been implicated as a cause of lung defects. However, the effect of cobalt on airway smooth muscle (ASM) cells has not been analyzed in detail. In this article, we use primary cultures of ASM cells from rabbit trachea and show that exposure to cobalt chloride causes a rapid increase of the intracellular levels of hypoxia-inducible factor-1alpha, which is detected predominantly inside the nucleus. With the use of specific inhibitors, we demonstrate that induction of hypoxia-inducible factor-1alpha by cobalt depends on active protein synthesis but not transcription. Furthermore, wortmannin, LY294002, and N-acetyl-L-cysteine inhibit the effect of cobalt, suggesting that it involves the phosphatidylinositol 3 kinase pathway and production of reactive oxygen species. Interestingly, cobalt chloride attenuates the contractile response of rabbit airways induced by potassium chloride, but not by acetylcholine, suggesting a link between the cellular response to hypoxic stimuli and the contractile properties of ASM cells.


Detection and evaluation of elevated lead release from service lines: a field study.
Comparative stagnation sampling conducted in 32 homes in Chicago, Illinois with lead service lines demonstrated that the existing regulatory sampling protocol under the U.S. Lead and Copper Rule systematically misses the high lead levels and potential human exposure. Lead levels measured with sequential sampling were highest within the lead service lines, with maximum values more than four times higher than Chicago's regulatory compliance results using a first-draw sampling protocol. There was significant variability in lead values from different points within individual lead service lines and among different lead service line sites across the city. Although other factors could also influence lead levels, the highest lead results most often were associated with sites having known disturbances to the lead service lines. This study underscores the importance and interdependence of sample site selection, sampling protocol, and other factors in assessing lead levels in a public water system.


Costs of asthma among US working adults.
To evaluate the effect of asthma on direct and indirect costs among US working adults. A case-control retrospective analysis was conducted. Data between January 1, 2003, and December 31, 2006, among patients aged 18 to 64 years with vs without asthma were extracted from MarketScan Research Databases. Patients with chronic obstructive pulmonary disease or emphysema were excluded, and all patients were required to have 12-month continuous enrollment before and after the index date. Outcomes included direct medical costs, the number of absence days, the number of short-term disability days, and associated indirect costs. Patients with asthma were propensity score-matched to patients without asthma using nearest neighbor 1:1 with caliper. Subsequent multivariate analysis was conducted on matched samples to examine the marginal effect of asthma on direct and indirect costs. A total of 13,379 patients with asthma were propensity score-matched to 13,379 patients without asthma; in each cohort, 3453 patients had absence eligibility, and 8497 patients had short-term disability eligibility. Direct costs for patients with asthma were $3762, and indirect costs were $4572. Compared with the matched cohort without asthma, patients with asthma had $1785 higher direct medical expenditures (P <.001). Incremental indirect costs were $191 for absenteeism (P = .007) and $172 for short-term disability (P<.001). Compared with patients without asthma, patients with asthma experience significantly higher direct medical costs and, although modest, significantly higher work loss. Treatments or interventions that prevent or reduce asthma symptoms may have a beneficial effect on medical costs and work absenteeism.


Lunar phase does not influence surgical quality.
10.5% of the German population believes in the effects of lunar phase on disease. The topic is hot in German TV program. It is believed that at new moon the rate of bleeding complications is increased and operations during the waning phase of the moon would be best to avoid complications, pain and scaring. To our knowledge the effect of lunar phase has not been studied in ambulatory surgery. 782 patients were evaluated for complications and perception of the personal health after herniotomy, haemorrhoidectomy and crossectomy with partial vein stripping with or without phlebectomy as part of a quality control study. A questionnaire has been sent out to the patients asking the patient to rate postoperative pain, pain medication, restriction of daily activity, mental health and emotion, status of complaints after the operation. In 782 patients (mean age 50 years) 866 operations were performed. There were no major complications and only in 3.71% minor complications (local bleeding, haematoma, inflammation, abscess, seroma, lymphatic fistula, dehiscence) were observed. The operations were equally distributed to the lunar phases. Complications and patient's subjective perception of pain, restriction of daily activity, mental health and emotion, status of complaints after the operation were not associated with a lunar phase. The hypothesis that lunar phase influences the outcome of ambulatory operations is not valid. With regard to the organization of operations in the hospital and the patient's uncertainty to decide the right time the lunar phase philosophy may have an socio-economic impact not yet understood.


[Consensus document about the nutritional evaluation and management of eating disorders: anorexia nervosa].
Anorexia nervosa is the most common psychiatric disease among young women and it is assumed to be of multifactorial origin. Diagnostic criteria have recently been modified; therefore amenorrhea has ceased to be a part of them. This disease shows a large variability in its presentation and severity which conditions different therapeutic approaches and the need to individualize the treatment, thus it is indispensable a multidisciplinary approach. The goals are to restore nutritional status (through an individualized diet plan based on a healthy consumption pattern), treat complications and comorbidities, nutritional education (based on healthy eating and nutritional patterns), correction of compensatory behaviors and relapse prevention. The treatment will vary according to the patient's clinical situation, and it may be performed in outpatient clinics (when there is clinical stability), in a day hospital or ambulatory clinic (intermediate mode between traditional outpatient treatment and hospitalization) or hospitalization (when there is outpatient management failure or presence of serious medical or psychiatric complications). Artificial nutrition using oral nutritional supplements, enteral nutrition and exceptionally parenteral nutrition may be necessary in certain clinical settings. In severely malnourished patients the refeeding syndrome should be avoided. Anorexia nervosa is associated with numerous medical complications which determines health status, life quality, and is closely related to mortality. There is little clinical evidence to assess the results of different treatments in anorexia nervosa, when most of the recommendations are being based on expert consensus.


Syndromic craniosynostosis, fibroblast growth factor receptor 2 (FGFR2) mutations, and sacrococcygeal eversion presenting as human tails.
There have been 23 previously published cases of patients with syndromic craniosynostosis and human tails. In many of these, the tail was composed of prominent coccygeal and sacral vertebrae, curved in a retroverted instead of in the normal anterograde fashion. This has been termed sacrococcygeal eversion. In those cases in which genetic testing results are reported, there were fibroblast growth factor receptor 2 (FGFR2) mutations. We present three patients with Pfeiffer syndrome and sacrococcygeal eversion. Two had genetic testing and both had FGFR2 mutations, one of them a novel mutation in patients with syndromic craniosynostosis and sacrococcygeal eversion. We also briefly review the literature on craniosynostosis and human tails. All but one reported patient has had either Pfeiffer, Crouzon, or Beare-Stevenson syndrome. Most patients, including ours, have had severe manifestations of their syndrome. Although the pathogenesis of sacrococcygeal eversion is unknown, a similarly posteriorly curved tail bud develops in normal human embryos during the second month of gestation. Perhaps increased FGFR2 activation during this embryonic period leads to abnormal differentiation or regression of the tail bud and, in turn, sacrococcygeal eversion, in certain patients with severe syndromic craniosynostosis.


Invited Commentary: Self-Control Is a Virtue.
The case-crossover design, introduced in 1991 by Malcolm Maclure (Am J Epidemiol. 1991;133(2):144-153), provided a precise and powerful tool for studying short-term effects of transient triggering exposures on abrupt outcomes like myocardial infarction. The design is an example of "self-control." One compares case-time intervals that include experiences that came just before the health event with control-time intervals that capture comparable experiences more remote from the event. Methodologists have since tweaked the general approach, recognizing issues that need to be considered to guard against time-driven confounders. I discuss opportunities for possible expansion and further mining of the data from this ingenious design.


L1 Cell Adhesion Molecule Promotes Migration and Invasion via JNK Activation in Extrahepatic Cholangiocarcinoma Cells with Activating KRAS Mutation.
Extrahepatic cholangiocarcinoma (ECC), a malignant tumor of biliary origin, has a poor prognosis with limited treatment options. The KRAS oncogene is the most commonly mutated gene in ECC and one of the factors that predicts a poor prognosis and low survival rate. L1 cell adhesion molecule (L1CAM) is expressed in ECC cells and acts as an independent poor prognostic factor in predicting patient survival. In this study we investigate the functional significance of L1CAM in ECC cells with activating KRAS mutation. We selected an ECC cell line, EGI-1, with activating KRAS mutation, and then confirmed its expression of L1CAM by RT-PCR, western blot analysis, and flow cytometry. The suppression of L1CAM expression (using a specific lentivirus-delivered shRNA) significantly decreased the migratory and invasive properties of EGI-1 cells, without altering their proliferation or survival. Analyses of signaling effectors in L1CAM-depleted and control EGI-1 cells indicated that L1CAM suppression decreased the levels of both phosphorylated MKK4 and total MKK4, together with c-Jun N-terminal kinase (JNK) phosphorylation. Further, exposure to a JNK inhibitor (SP600125) decreased migration and invasion of EGI-1 cells. These results suggest that L1CAM promotes cellular migration and invasion via the induction of MKK4 expression, leading to JNK activation. Our study is the first to demonstrate a functional role for L1CAM in ECC carrying the activating KRAS mutation. Given that KRAS is the most commonly mutated oncogene in ECC, L1CAM may serve as an attractive therapeutic target for ECC cells with activating KRAS mutation.


The individual time trial as an optimal control problem.
In a cycling time trial, the rider needs to distribute his power output optimally to minimize the time between start and finish. Mathematically, this is an optimal control problem. Even for a straight and flat course, its solution is non-trivial and involves a singular control, which corresponds to a power that is slightly above the aerobic level. The rider must start at full anaerobic power to reach an optimal speed and maintain that speed for the rest of the course. If the course is flat but not straight, then the speed at which the rider can round the bends becomes crucial.


Ion Pairing and Co-facial Stacking Drive High-Fidelity Bisulfate Assembly with Cyanostar Macrocyclic Hosts.
Hydroxyanions pair up inside CH H-bonding cyanostar macrocycles against Coulombic repulsions and solvation forces acting to separate them. The driving forces responsible for assembly of bisulfate (HSO4- ) dimers are unclear. We investigated them using solvent quality to tune the contributing forces and we take advantage of characteristic NMR signatures to follow the species distributions. We show that apolar solvents enhance ion pairing to stabilize formation of a 2:2:2 complex composed of π-stacked cyanostars encapsulating the [HSO4 ⋅⋅⋅HSO4 ]2- dimer and endcapped by tetrabutylammonium cations. Without cations engaged, a third macrocycle can be recruited with the aid of solvophobic forces in more polar solvents. The third macrocycle generates a more potent electropositive pocket in which to stabilize the anti-electrostatic anion dimer as a 3:2 assembly. We also see unprecedented evidence for a water molecule bound to the complex in the acetonitrile solution. In methanol, OH H-bonding leads to formation of 2:1 complexes by bisulfate solvation inside the macrocycles inhibiting anion dimers. Knowledge of the driving forces for stabilization (strong OH⋅⋅⋅O H-bonding, CH H-bonding, ion pairs, π-stacking) competing with destabilization (Coulomb repulsion, solvation) allows high-fidelity selection of the assemblies. Thermodynamic stabilization of hydroxyanion dimers also demonstrates the ability to use macrocycles to control ion speciation and stoichiometry of the overall assemblies.


Transplacental disposition and teratogenic effects of chlorpyrifos in rats.
Rats were orally fed with different doses viz. 9.6, 12 and 15 mg/kg/d from GD 0-20 and examined for evidence of fetotoxicity and teratogenecity to evaluate the potential effects of technical chlorpyrifos (97%). Fetotoxic effects were not observed at tested dose levels as evidenced by number of implantations, number of corpora lutea and live fetuses/dam, but significant alterations were noted in percent delta resorption and fetal weight. There were no major malformations, but some minor anomalies such as reduced parietal ossification and absence of phalanges found significant in high dose were not considered as compound-related effects. On the other hand the accumulation of chlorpyrifos residue in dams was more in brain (0.0328 micro g/g) than in liver (0.0071 micro g/g).The level of residue in fetuses was in the following order : liver (0.0531 micro g/g) > brain (0.0364 micro g/g) >placenta (0.040 micro g/g) > amniotic fluid (0.0010 micro g/g). Although, the total residue was higher in fetuses (0.0447 micro g/g) than in dams (0.0120 micro g/g), the absence of abnormalities in fetal gross morphology, visceral and skeleton suggest that technical chlorpyrifos at tested dose levels is non-teratogenic in rats.


Monitoring and modelling of exposure to ethanol in hairdressing salons.
Personal exposure to solvents was studied among hairdressers in 28 salons in two regions during two seasons in The Netherlands. Ethanol was used as a marker for solvent exposure. Auxiliary data, such as salon and work characteristics, meteorological conditions and information on the presence of control measures, were collected during the measurements. The average exposure to ethanol was almost a factor of 200 below the occupational exposure limit, but differences in average ethanol concentrations up to a factor of 30 were present between salons. Exposure concentrations were significantly higher on Fridays than on other days of the week. Contrary to expectation, exposures were somewhat lower in the spring than in the summer and in an urban than a semi-rural area. An empirical statistical model based on exposure data collected during the first measurement period appeared not to be valid for the encountered circumstances in the second measurement period. An alternative classification scheme based on two easily obtainable salon and task characteristics was elaborated. This scheme will be applied in an ongoing epidemiological study on reproductive disorders among hairdressers and their offspring.


[The establishment and evaluation of the model rats of blood stasis and heat accumulation syndrome].
To establish a rat model of blood stasis and heat accumulation syndrome in accordance with the Chinese medicine (CM) theoretic features. Thirty male SD rats were randomly divided into the normal group, the model group, and the danshen root group, 10 in each. Rats in the danshen root group were given danshen decoction at 13.5 g/kg by gastrogavage, with the volume of 20 mL/kg, twice daily for 7 successive days. As for rats in the normal group and the model group, equal volume of pure water was given to them by gastrogavage, twice daily for 7 successive days. On the 4th day of medication, carrageen at 50 mg/kg was peritoneally injected to rats in the model group and the danshen root group, once daily for 3 successive days. Twenty-four h after the last injection, 20% dry yeast suspension (10 mL/kg) was given to the rats by subcutaneous injection. The indictors such as body temperature, tongue figure, tail ecchymosis, skin color of the ears and four limbs, microcirculation indicators, and hemorheological indicators were observed 6 h later. Compared with the normal group, red and purple tongue, longer and thicker arteries and veins under the tongue, red and purple claw color, red ear flap edge, obvious ecchymosis of the tail occurred in rats of the model group (P<0.01), with obviously increased body temperature (P<0.01). The blood velocity of the microcirculation in the ear flap obviously decreased. The hemorheology tests showed that the whole blood viscosity (high, middle, and low), hematocrit, and erythrocyte electrophoretic time obviously increased, red blood cell deformation index obviously deceased, showing statistical difference (P<0.01, P<0.05). Compared with the model group, the length of ecchymosis in the tail obviously decreased in rats of the danshen root group. The blood velocity score of the microcirculation obviously increased. The hemorheology tests showed that the whole blood viscosity (high, middle, and low), hematocrit, and erythrocyte electrophoretic time obviously decreased, red blood cell deformation index obviously increased, showing statistical difference (P<0.05, P<0.01). The rat model of blood stasis and heat accumulation syndrome established with carrageen and dry yeast suspension injection had obvious features, with good reproducibility and stability. It could be used in the study of CM basic theories, screening of Chinese herbs, and the theories of Chinese-drug properties.


Female marmosets' behavioral and hormonal responses to unfamiliar intruders.
The endocrine control mechanisms for female mammalian aggression have been largely unstudied. Although it has been proposed that androgens may modulate female aggressive behavior in a similar manner to males, very little conclusive evidence exists. Previous work in male marmosets found that post-encounter increases in testosterone (T) were dependent on the intensity of aggression displayed during the aggressive encounter. We exposed female marmosets (Callithrix kuhlii), a monogamous and biparental primate, to aggressive interactions with unfamiliar intruders. Individual female marmosets exhibited changes in T and estradiol (E(2) ) that are associated with aggressiveness dependent on the intensity of aggression displayed as well as their role during the encounter. Resident females exhibited increased E(2) immediately following an encounter in which they displayed high rates of aggression. If resident females received high rates of aggression from the intruder, the resident displayed increased T 24 hr following the encounter. Interestingly, if the female was an intruder in the encounter, the intensity of her aggression was associated with increased cortisol immediately following the trials, whereas received aggression was associated with increased T and E(2) immediately following the trial. Female primates do exhibit situation-dependent changes in gonadal steroids in association with aggression that may serve to prime them for future aggressive interactions.


Partners in crime: bidirectional transcription in unstable microsatellite disease.
Nearly two decades have passed since the discovery that the expansion of microsatellite trinucleotide repeats is responsible for a prominent class of neurological disorders, including Huntington disease and fragile X syndrome. These hereditary diseases are characterized by genetic anticipation or the intergenerational increase in disease severity accompanied by a decrease in age-of-onset. The revelation that the variable expansion of simple sequence repeats accounted for anticipation spawned a number of pathogenesis models and a flurry of studies designed to reveal the molecular events affected by these expansions. This work led to our current understanding that expansions in protein-coding regions result in extended homopolymeric amino acid tracts, often polyglutamine or polyQ, and deleterious protein gain-of-function effects. In contrast, expansions in noncoding regions cause RNA-mediated toxicity. However, the realization that the transcriptome is considerably more complex than previously imagined, as well as the emerging regulatory importance of antisense RNAs, has blurred this distinction. In this review, we summarize evidence for bidirectional transcription of microsatellite disease genes and discuss recent suggestions that some repeat expansions produce variable levels of both toxic RNAs and proteins that influence cell viability, disease penetrance and pathological severity.


[Ophthalmology in 2016 : the advent of ocular biomarkers].
Precision medicine is the future. In all fields of medicine, optimized therapy aims at identifying individuals at risks in order to prevent diseases, to identify specific molecular targets in a specific patient, at a specific time, to administer optimized treatment with less side effects. To achieve this ambitious aim, biomarkers, which should be specific and sensitive predictive indicators of diseases, or of response to treatment or of a state of evolution of the disease, must be identified. The eye offers an easy access organ to collect directly media or tissue, which can serve to identify such markers. This paper summarizes recent advances in the identification of ocular biomarkers of ocular diseases but also of brain diseases.


Towards Concurrent Data Transmission: Exploiting Plasmid Diversity by Bacterial Conjugation.
The progress of molecular communication (MC) is tightly connected to the progress of nanomachine design. State-of-the-art states that nanomachines can be built either from novel nanomaterials by the help of nanotechnology or they can be built from living cells which are modified to function as intended by synthetic biology. With the growing need of the biomedical applications of MC, we focus on developing bio-compatible communication systems by engineering the cells to become MC nanomachines. Since this approach relies on modifying cellular functions, the improvements in the performance can only be achieved by integrating new biological properties. A previously proposed model for molecular communication is using bacteria as information carriers between transmitters and receivers, also known as bacterial nanonetworks. This approach has suggested encoding information into the plasmids inserted into the bacteria which leads to extra overhead for the receivers to decode and analyze the plasmids to obtain the encoded information. Another scheme, which is proposed in this paper, is to determine the digital information transmitted based on the quantity of bacteria emitted. While this scheme has its simplicity, the major drawback is the low-data rate resulting from the long propagation of the bacteria. To improve the performance, this paper proposes a distributed modulation scheme utilizing three bacterial properties, namely, engineering of plasmids, conjugation, and bacterial motility. In particular, genetic engineering allows us to engineer the different combinations of genes representing the different series of bits. When compared with binary density modulation and the M-ary density modulation, it is shown that the distributed modulation scheme outperforms the other two approaches in terms of bit error probability as well as the achievable rate for varying quantity of bacteria transmitted, distances, as well as time slot length.


Evolution of the Helicobacter pylori vacuolating cytotoxin in a human stomach.
We describe two subclones of Helicobacter pylori, isolated contemporaneously from a human stomach, which differ markedly in the vacuolating cytotoxin gene, vacA, but whose near identity in sequences outside this locus implies a very recent common origin. The differences are consistent with homologous recombination with DNA from another strain and result in a changed vacA midregion and, importantly, in changed toxicity.


Blinding and sham control methods in trials of physical, psychological, and self-management interventions for pain (article II): a meta-analysis relating methods to trial results.
Sham interventions in randomized clinical trials (RCTs) of physical, psychological, and self-management (PPS) therapies for pain are highly variable in design and believed to contribute to poor internal validity. However, it has not been formally tested whether the extent to which sham controls resemble the treatment under investigation consistently affects trial outcomes, such as effect sizes, differential attrition, participant expectancy, and blinding effectiveness. Placebo- or sham-controlled RCTs of PPS interventions of clinical pain populations were searched in 12 databases. The similarity of control interventions to the experimental treatment was rated across 25 features. Meta-regression analyses assessed putative links between employed control interventions, observed effect sizes in pain-related outcomes, attrition, and blinding success. The sample included 198 unique control interventions, dominated by manual therapy and chronic musculoskeletal pain research. Meta-analyses indicated small-to-moderate benefits of active treatments over control interventions, across subgroups of manual therapies, exercise, and rehabilitation, and psychological intervention trials. Multiple meta-regression modelling demonstrated that similarity between sham control and tested interventions predicted variability in pain-related outcomes, attrition, and blinding effectiveness. Influential variables were differences relating to the extent of intervention exposure, participant experience, and treatment environments. The results support the supposed link between blinding methods and effect sizes, based on a large and systematically sourced overview of methods. However, challenges to effective blinding are complex and often difficult to discern from trial reports. Nonetheless, these insights have the potential to change trial design, conduct, and reporting and will inform guideline development.


Arthroscopically-Assisted Latissimus Dorsi Transfer for Irreparable Rotator Cuff Insufficiency: Modes of Failure and Clinical Correlation.
The main objective of this retrospective study was to analyze the rate and modes of failure of latissimus dorsi transfer (LDT). The secondary objective was to evaluate whether a rupture of the transfer was associated with a worse outcome. During a 2-year period, we performed consecutive LDTs either for irreparable posterior-superior rotator cuff tears (RCTs) or for failed prior repair. All the LDTs were performed by a single surgeon. All transfers were arthroscopically assisted and fixed as a tubularized LD tendon in a bone tunnel inside the humeral head. Three metal clips were placed systematically intraoperatively in the tubularized tendon at a fixed distance of 2, 4, and 6 cm from the tip of the tendon. Immediate postoperative standard anteroposterior radiographs were performed and the position of the metal clips was compared with their position on radiographs performed at 6 weeks and 3 and 24 months postoperatively. Constant, Subjective Shoulder Value (SSV), Simple Shoulder Test (SST), Activities of daily living requiring active external rotation (ADLER), visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES) scores and patient's subjective satisfaction (assessed by self-questionnaire) at last follow-up were compared between patients who had a rupture of the transfer and those who did not. Sixty-six patients were included. Six of 66 patients (9%) were lost to follow-up. There were 11 complications (18.3%) in the global series (10 hematoma and 1 subscapularis retear). At a mean 35.2 months (range 24-50 months), there were 23/60 cases of rupture (38%). The 7 scores and the satisfaction reported were significantly lower for patients who had a rupture of the transfer versus those who had an intact transfer: Constant score, 42.8 versus 68.7 (P = .001); SSV, 48.9 versus 71.6 (P = .001); SST, 4.8 versus 8.4 (P = .012); ADLER, 19.7 versus 26.7 (P = .005); VAS, 3.7 versus 2.3 (P = .082); ASES, 55.4 versus 74.8 (P = .056); and 13% of either satisfied or very satisfied patients versus 78% (P < .001). The rate of rupture of LDT is high (38%). With complete healing of LDT, the outcome is significantly lower in those with rupture compared with those without rupture, showing that LDT can efficiently treat massive and irreparable RCT. Level IV, case series treatment study.


Ectopic expression of a homeobox gene changes cell fate in Xenopus embryos in a position-specific manner.
We have injected XIHbox 6 mRNA together with the lineage tracer colloidal gold into individual dorso-anterior blastomeres of the 32-cell stage Xenopus embryo and analyzed their cell fate during embryogenesis. While the developing tadpoles appeared entirely normal, the fate of the progeny of the injected blastomere was altered. In the brain injected cells failed to differentiate terminally, as indicated by a loss of labeled cranial nerves. Differentiation of spinal nerves remained unaffected. Fate change in the CNS occurred at about the time of normal XIHbox 6 protein expression. In addition, progeny of injected blastomeres gained head epidermal fate and lost anterior notochord fate as a result of altered cell migrations during gastrulation. The results show that a homeodomain protein is capable of altering cell fate in a position-specific and cell-autonomous manner in Xenopus embryos. The experimental approach used here should be applicable to other molecules specifying cell fate.


Hormone profile & polycystic ovaries in acne vulgaris.
Thirty women with acne vulgaris, 20 of whom had moderate/severe acne and ten mild acne, and ten controls matched for age were studied. Grade of hirsutism and menstrual irregularities, if any, were recorded. Hormonal measurements included gonadotropins, LH/FSH, prolactin, testosterone and androstenedione in the early follicular phase and progesterone in the luteal phase to assess ovulation. Pelvic ultrasound examination for polycystic ovaries (PCO) was done in all subjects. Sixteen patients with moderate/severe acne and one with mild acne had polycystic ovaries on ultrasound. Patients with moderate/severe acne with polycystic ovaries had high luteinizing hormone, prolactin, testosterone and androstenedione and LH/FSH ratio of more than three. Patients with polycystic ovaries were detected to have at least one hormonal abnormality.


Biotin supplementation of practical diets for channel catfish.
A purified diet and two practical-type diets were each evaluated with supplemental biotin (1 mg/kg), without supplemental biotin, and with a biotin antagonist (freeze-dried egg white) for channel catfish (Ictalurus punctatus) over a 17-week feeding period. Omission of supplemental biotin from the casein-dextrin purified diet, with or without egg white, resulted in anorexia, reduced growth rate, lighter skin, hypersensitivity and reduced liver pyruvate carboxylase activity by this fish. Omission of supplemental biotin from either practical diet, one containing basically soybean meal and corn and another containing basically soybean meal, corn and menhaden fishmeal , caused none of these deficiency signs. The ratio of biotin to indigestible dry matter in feces was lower than that in the diet for all fish, indicating little or no synthesis of biotin by the intestinal microflora in channel catfish. Levels of total biotin, measured microbiologically, in the all-plant and in the plant- fishmeal diets were 0.37 and 0.33 mg/kg, respectively. These results indicate that practical diets for channel catfish made from the commonly used ingredients, soybean meal, corn and menhaden fishmeal , do not need supplemental biotin.


Identification and function of exchange proteins activated directly by cyclic AMP (Epac) in mammalian spermatozoa.
The role of cAMP in spermatic functions was classically thought to be mediated exclusively through the activation of Protein Kinase A (PKA). However, it has recently been shown that cAMP also exerts its effects through a PKA-independent pathway activating a family of proteins known as Epac proteins. Therefore, many of the spermatic functions thought to be regulated by cAMP through the activation of PKA are again under study. We aimed to identify and to investigate the role of Epac proteins in spermatozoa using a specific permeable analog (8-Br-2'-O-Me-cAMP). Also, we aimed to study its relationship with E-cadherin, an adhesion protein involved in fertility. Our results demonstrate the presence and sub-cellular distribution of Epac 1 and Epac 2 in mammalian spermatozoa. Capacitation and the acrosome reaction induced a change in the localization of Epac proteins in sperm. Moreover, incubation with 8-Br-2'-O-Me-cAMP prompted an increase in Rap1 activation, in the scrambling of plasma membrane phospholipids (necessary for the capacitation process), the acrosome reaction, motility, and calcium mobilization, when spermatozoa were incubated in acrosome reaction conditions. Finally, the activation of Epac proteins induced a change in the distribution of E-cadherin. Therefore, the increase in the acrosome reaction, together with the increase in calcium (which is known to be essential for fertilization) and the Epac nteraction with E-cadherin, might indicate that Epac proteins have an important role in gamete recognition and fertilization.


Clinical significance of lncRNA MIR31HG in melanoma.
The aim of this study was to explore the expression of long non-coding RNA (lncRNA) MIR31HG in malignant melanoma (MM), and to investigate its clinical significance. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA MIR31HG in MM tissues and cells. The relationship between lncRNA MIR31HG expression and the clinicopathological characteristics was analyzed. Furthermore, the cell counting kit-8 (CCK-8) and the transwell assays were performed to assess the effect of MIR31HG on cell proliferation and metastasis in vitro, respectively. The expression of MIR31HG was significantly upregulated in MM tissues and cells. To explore the relationship between MIR31HG expression and clinical features, the patients were divided into two groups according to the mean expression of MIR31HG, including high expression group and low expression group. The subsequent results indicated that MIR31HG expression was correlated with lymph nodes metastasis, distal metastasis, and TNM stage. The multivariate analysis indicated that a high expression of MIR31HG could be used as an independent prognostic factor for MM. MIR31HG low-expression cells were constructed in vitro. Compared with the control cells, the cells with low expression of MIR31HG showed significantly low malignancy, including decreased cell proliferation rate and migration and invasion rates. LncRNA MIR31HG was a novel factor involved in MM progression, which could be used as a potential biomarker and therapeutic target for MM.


Imaging of maxillary osteoradionecrosis.
Over a 3-year period, four cases of maxillary osteoradionecrosis were diagnosed in patients undergoing radiotherapy for nasopharyngeal carcinoma at the Queen Mary Hospital, Hong Kong, giving an estimated incidence of 0.8%. Patients with this complication presented after a mean period of 34 months post-radiotherapy. Risk factors that were identified were dental problems, and more than one full course of radical radiotherapy. Serial CT scans in the axial and coronal planes were useful in demonstrating the development, extent and features of maxillary osteoradionecrosis such as bony sclerosis, the destruction of maxillary antral walls and adjacent bony structures, and in excluding recurrent tumour.


Changes in alpha 2-adrenoceptors on vascular smooth muscle and neural membranes following hypertension induced by renal ischemia.
alpha 2-Adrenoceptors were characterized on neural and vascular membranes from 2-kidney-1-clip renal hypertensive (RHT) and normotensive (NT) rats. Rats were sacrificed 6 weeks after induction of renal ischemia, and the specific binding of 3H-clonidine to smooth muscle membranes form tail arteries and neural membranes from various brain regions was examined. Additionally, isometric contractions of helically cut tail artery strips produced by various alpha-adrenoceptor agonists were measured. Scatchard analysis indicated an increased number of high-affinity binding sites on the smooth muscle membranes from RHT rats (Bmax = 43.5 +/- 1.4 fmol/mg protein) compared to that from the NT rats (25.4 +/- 3.8 fmol/mg protein). An increased contractile sensitivity to clonidine was also observed in tail artery strips from RHT rats (EC50 for RHT = 3.04 x 10(-8) M; NT = 1.52 x 10(-7) M). In neural tissue, the number of alpha 2-adrenoceptor-binding sites was significantly increased in the locus coeruleus from RHT rats, but not in the amygdala, hypothalamus, parietal cortex, hippocampus or lower brain stem. These results demonstrate that renal ischemia produces changes in both peripheral and neural alpha 2-adrenoceptor density. The increase in smooth muscle alpha 2-adrenoceptors might also provide a partial explanation for the supersensitivity to adrenergic agonists in this model of hypertension.


Subacute Hypophysitis with Panhypopituitarism as First Presentation of HIV and Syphilis Coinfection.
Infection by Treponema pallidum still represents a clinical challenge due to its various forms of presentation. HIV coinfection added diversity and changed the natural history of syphilis as a systemic infection. We present a rare case of subacute hypophysitis and panhypopituitarism due to an early active neurosyphilis in a previously unknown HIV coinfected patient.


Treating Tumors by Molecular Profile, Not Type.
Preliminary findings from MyPathway, an ongoing phase II basket trial, indicate that matching molecular abnormalities of patients' tumors to relevant targeted therapies-albeit outside a given drug's FDA-approved indication-is both feasible and promising. Notably, patients with HER2-amplified colorectal, bladder, and biliary cancers responded well to the combination of trastuzumab and pertuzumab.


Expression Pattern of Matrix Metalloproteinase 20 (MMP20) in Human Tumors.
Matrix metalloproteinase 20 (MMP20) is a member of the family of matrix metalloproteinases. Under normal conditions the expression of MMP20 is restricted to ameloblasts and odontoblasts. In order to identify a possible expression of MMP20 under pathological conditions, we investigated three major human tumor entities, i.e. colon, breast and lung tumors, on the mRNA and protein level. Real-time RT-PCR and immunocytochemical analyses of established human tumor cell lines were employed for our study; immunohistochemical analysis was performed on both primary tumors and normal control tissues. MMP20 was identified on both the mRNA and the protein level in breast MCF-7, colon HT-29, and lung A549 cell lines. MMP20 was also detected in primary tumor tissue by immunohistochemistry. MMP20 is a new potential candidate for tumor diagnosis or therapy.


The Next Frontier of Remote Patient Monitoring: Hospital at Home.
Remote patient monitoring (RPM) has shown promise in aiding safe and efficient remote care for chronic conditions; however, its use remains more limited within the hospital at home (HaH) model of care despite a significant opportunity to increase patient eligibility, improve safety, and decrease costs. HaH could achieve these goals by further adopting the 3 primary modalities of RPM (ie, vital sign, continuous single-lead electrocardiogram, and fall monitoring). With only 2 in-person vital sign checks required per day, HaH patient eligibility is currently often limited to lower-acuity cases. The use of vital sign RPM within HaH could better match the standard clinical practice of vital sign checks every 4-8 hours and enable safe care for appropriate moderate-acuity medical and surgical floor-level patients not traditionally enrolled in HaH. Robust, efficient collection of more frequent vital signs via RPM could expand patient eligibility for HaH and create a digital health safety net that enables high quality care. Similarly, our experience at Massachusetts General Hospital has demonstrated that appropriate use of continuous single-lead electrocardiogram RPM can also expand HaH enrollment, particularly for patients with acute decompensated heart failure. Through increasing enrollment of patients in HaH, RPM stands to enable more patients to reap the potential safety benefits of home hospitalization, including decreased rates of delirium and hospital-acquired infections, and better avoid aspects of posthospital syndrome. Furthermore, instituting fall detection RPM allows care teams to further HaH patient safety during their episode of acute care and develop enhanced mitigation strategies to avoid falls post home hospitalization. RPM also has the potential to assist HaH in achieving greater economies of scale and decreasing direct variable costs. By expanding HaH eligibility, RPM could enable HaH programs, which have traditionally operated under capacity, to care for a larger census and decrease allocated fixed costs per hospitalization. Additionally, RPM for HaH could further optimize hybrid in-home and remote nurse or physician evaluations, decreasing costs on a per-episode basis by up to an estimated 3.5%. Overall, RPM holds great promise to increase patient eligibility and patient safety while decreasing costs. However, it is in its infancy in achieving its potential to advance the HaH model of care; further research and experience that inform operational and technical as well as policy considerations are needed.


Paclitaxel for non-small cell lung cancer.
Paclitaxel, a tubulin-binding agent, is widely used for the treatment of non-small cell lung cancer (NSCLC). The combination of paclitaxel and a platinum compound is an approved regimen for the treatment of advanced NSCLC. The dose-limiting toxicity of paclitaxel is myelosuppression when administered on a prolonged infusion schedule, whereas neuropathy is more common with short infusions. Although the 3-weekly schedule of paclitaxel is the commonly utilised regimen for the treatment of advanced NSCLC, the weekly regimens appear to be associated with lesser myelosuppression and neuropathy. A randomised clinical trial is currently underway to compare the efficacy of the weekly versus 3-weekly regimen of paclitaxel, in combination with carboplatin for the treatment of advanced NSCLC. The radiosensitising effect of paclitaxel has led to its incorporation into multi-modality treatment of NSCLC patients in combination with thoracic radiation. Paclitaxel has also demonstrated synergistic interaction with several molecularly-targeted agents and is at present being evaluated in the neoadjuvant and adjuvant treatment settings for early stage NSCLC.


Effect of site-specific modification on restriction endonucleases and DNA modification methyltransferases.
Restriction endonucleases have site-specific interactions with DNA that can often be inhibited by site-specific DNA methylation and other site-specific DNA modifications. However, such inhibition cannot generally be predicted. The empirically acquired data on these effects are tabulated for over 320 restriction endonucleases. In addition, a table of known site-specific DNA modification methyltransferases and their specificities is presented along with EMBL database accession numbers for cloned genes.


Human Cdc14A reverses CDK1 phosphorylation of Cdc25A on serines 115 and 320.
Human Cdc14A is an evolutionary conserved dual-specificity protein phosphatase that reverses the modifications effected by cyclin-dependent kinases and plays an important role in centrosome duplication and mitotic regulation. Few substrates of Cdc14A have been identified, some of them with homologues in yeast that, in turn, are substrates of the Saccharomyces cerevisiae Cdc14 homologue, a protein phosphatase essential for yeast cell viability owing its role in mitotic exit regulation. Identification of the physiological substrates of human Cdc14A is an immediate goal in order to elucidate which cellular processes it regulates. Here, we show that human Cdc14A can dephosphorylate Cdc25A in vitro. Specifically, the Cdk1/Cyclin-B1-dependent phosphate groups on Ser115 and Ser320 of Cdc25A were found to be removed by Cdc14A. Cdc25A is an important cell cycle-regulatory protein involved in several cell cycle transitions and checkpoint responses and whose function and own regulation depend on complex phosphorylation/dephosphorylation-mediated processes. Importantly, we also show that the upregulation of Cdc14A phosphatase affects Cdc25A protein levels in human cells. Our results suggest that Cdc14A may be involved in the cell cycle regulation of Cdc25A stability.


Studies on the competence of single cells to produce antibodies of two specificities.
Two series of experiments were performed, utilizing a modification of the hemolysin plaque technique which registers 19S antibody, in an attempt to determine the frequency of cells capable of simultaneously producing antibody to two non-cross-reacting antigens. Mice were immunized i.v. with rabbit and camel RBC and their spleens assayed for cells producing antibody against both antigens. 16,904 cells producing antibody of one or the other specificity, from 26 mice, were counted. Not one cell was detected which produced antibody of two specificities. Rabbits were immunized intradermally with HSA to which polyalanyl and p-azobenzenearsonate groups were chemically attached. The individual haptens, polyalanyl, and p-azobenzenearsonate groups were coupled to separate aliquots of SRBC, and the lymph nodes of immunized rabbits were assayed for cells releasing antibody against both haptens. In a study of 11 rabbits, after counting 27,845 cells producing antibody, we detected no "double" plaques.


Clinical periodontal and microbiologic parameters in patients with Crohn's disease with consideration of the CARD15 genotype.
Crohn's disease (CD) was reported to have oral manifestations. However, data on periodontal parameters and oral microbiology in CD are rare. Recent studies showed associations of variants in the caspase recruitment domain (CARD)15 gene with CD that are involved in the immune response toward bacterial products. Our aim is to investigate the periodontal status and prevalence of periodontal pathogens in patients with CD under consideration of the CARD15 polymorphism. Oral soft tissue alterations and periodontal parameters of 147 patients with CD were assessed. Subgingival plaque samples were analyzed for the periodontal pathogens Aggregatibacter actinomycetemcomitans (Aa; previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf; previously T. forsythensis), Prevotella intermedia (Pi), and Campylobacter rectus (Cr ) using dot-blot hybridization. CARD15 genotyping was performed with the a polymerase chain reaction (PCR) based assay. A total of 36.7% of patients had oral manifestations predominated by gingival swellings (27.2%) and hyperplastic lesions of the buccal mucosa (20.4%). The mean probing depth and mean clinical attachment level were 3.6 and 3.8 mm, respectively. A total of 57.8% of the patients had a Community Periodontal Index of Treatment Needs (CPITN) score 3, and 31.3% of had a CPITN score 4. The prevalence of Aa, Pg, Pi, Tf, and Cr was 76.9%, 62.6%, 79.6%, 64.6%, and 94.6%, respectively. Pi was significantly less frequent in carriers of CARD15 mutations compared to the wild type (69.7% versus 87.7%; P = 0.008). All other pathogens and clinical periodontal parameters did not differ significantly as to the CARD15 polymorphism. Our findings suggest that patients with CD have an increased prevalence and moderate severity of periodontitis. The colonization of periodontal pathogens, in particular Cr, might be of particular value for the periodontal manifestation of CD. Although a modulating impact on periodontal microbiota can be supposed, our data do not support the role of CARD15 in oral symptoms and periodontal lesions in patients with CD.


IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts.
Colonic subepithelial myofibroblasts (SEMFs) may play a role in the modulation of mucosal inflammatory responses. We investigated the effects of interleukin (IL)-17 on IL-6 and chemokine [IL-8 and monocyte chemoattractant protein (MCP)-1] secretion in colonic SEMFs. Cytokine expression was determined by ELISA and Northern blotting. Nuclear factor kappa B (NF-kappaB) DNA-binding activity was evaluated by electrophortetic gel mobility shift assay (EMSA). The activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting. IL-6, IL-8, and MCP-1 secretions were rapidly induced by IL-17. IL-17 induced NF-kappaB activation within 45 min after stimulation. A blockade of NF-kappaB activation markedly reduced these responses. MAPK inhibitors (SB-203580, PD-98059, and U-0126) significantly reduced the IL-17-induced IL-6 and chemokine secretion. The combination of either IL-17 + IL-1beta or IL-17 + tumor necrosis factor (TNF)-alpha enhanced cytokine secretion; in particular, the effects of IL-17 + TNF-alpha on IL-6 secretion were much stronger than the other responses. This was dependent on the enhancement of IL-6 mRNA stability. In conclusion, human SEMFs secreted IL-6, IL-8, and MCP-1 in response to IL-17. These responses might play an important role in the pathogenesis of gut inflammation.


Effect of a common reference plasma on the inter-laboratory variation of the measurement of total and free protein S: a collaborative study of the Dutch Working Group on Haemostasis Laboratory Diagnosis.
The comparability of test results for protein S between laboratories is hampered by a high inter-laboratory variability. The effect of the use and type of common reference plasma on the inter-laboratory variability of the total and free protein S measurement was evaluated. The results of 10 plasma samples measured against a centrally distributed frozen plasma and a centrally distributed lyophilized plasma were compared with those of various local reference plasmas regularly used by the 11 participating laboratories. The mean intra-assay coefficient of variation for total protein S in each laboratory varied from 3.8 to 12.8% (mean intra-assay CV of all laboratories: 7.4+/-2.3%); for free protein S this range was 3.1 to 13.3% (mean intra-assay CV of all laboratories: 6.6+/-2.7%). We confirmed the high inter-laboratory coefficient of variation (mean+/-SD) with the several local reference plasmas for both total protein S (13.4+/-5.6%; n = 10) and free protein S (17.1+/-7.5%: n = 11). For total protein S, the inter-laboratory CV was reduced to 11.5+/-4.8%, (p=0.05) by using a common frozen reference plasma, while it was increased to 16.8+/-3.4%, (p=0.022) using a common lyophilized reference plasma. For free protein S, these values decreased only statistically significantly for the common lyophilized reference plasma, to 15.1+/-6.0%, (p = 0.008). For free protein S, the dilution factor used was identified as a factor influencing the inter-laboratory variability. This study shows that, for both types of protein S measurements, using one frozen reference plasma shows a slight decrease in inter-laboratory variability, while a common lyophilized plasma shows inconsistent results. It is concluded that further investigation is necessary to examine other sources of variability to increase the comparability of laboratory results for both total and free protein S.


Specific antigen exclusion and non-specific facilitation of antigen entry across the gut in rats allergic to food proteins.
The intestinal absorption of ovalbumin and beta-lactoglobulin was measured in Hooded Lister rats which had previously been made allergic to ovalbumin, and in unimmunized controls. The antigens were introduced both together and separately into closed intestinal loops. Absorption of free ovalbumin, but not beta-lactoglobulin, was reduced in rats with anti-ovalbumin antibody, demonstrating antigen-specific immune exclusion despite the presence of reaginic antibody. In contrast, the absorption of beta-lactoglobulin was enhanced by the presence of ovalbumin in rats with IgE anti-ovalbumin, but not in unimmunized controls. These results suggest that macromolecular absorption may be increased in an antigen non-specific way in food allergy.


In vitro hypoglycemic effects of different insoluble fiber-rich fractions prepared from the peel of Citrus sinensis L. cv. Liucheng.
Insoluble fiber-rich fractions (FRFs), including insoluble dietary fiber, alcohol-insoluble solid, and water-insoluble solid, were isolated from the peel of Citrus sinensis L. cv. Liucheng. We found that these three FRFs could effectively adsorb glucose, retard glucose diffusion, and inhibit the activity of alpha-amylase to different extents. These mechanisms might create a concerted benefit in decreasing the rate of glucose absorption and eventually lower the concentration of postprandial serum glucose. The potential hypoglycemic effects of these FRFs suggested that they could be incorporated as low-calorie bulk ingredients in high-fiber foods to reduce calorie level and control blood glucose level.


Reconstitution of a functional IS608 single-strand transpososome: role of non-canonical base pairing.
Single-stranded (ss) transposition, a recently identified mechanism adopted by members of the widespread IS200/IS605 family of insertion sequences (IS), is catalysed by the transposase, TnpA. The transposase of IS608, recognizes subterminal imperfect palindromes (IP) at both IS ends and cleaves at sites located at some distance. The cleavage sites, C, are not recognized directly by the protein but by short sequences 5' to the foot of each IP, guide (G) sequences, using a network of canonical ('Watson-Crick') base interactions. In addition a set of non-canonical base interactions similar to those found in RNA structures are also involved. We have reconstituted a biologically relevant complex, the transpososome, including both left and right ends and TnpA, which catalyses excision of a ss DNA circle intermediate. We provide a detailed picture of the way in which the IS608 transpososome is assembled and demonstrate that both C and G sequences are essential for forming a robust transpososome detectable by EMSA. We also address several questions central to the organization and function of the ss transpososome and demonstrate the essential role of non-canonical base interactions in the IS608 ends for its stability by using point mutations which destroy individual non-canonical base interactions.


An Examination of How Gender May Relate to Communication Styles of Introversion and Extroversion in Nursing Students.
This research brief explores the relationship between introversion and extroversion communication styles and gender in nursing students. Although communication is integral for delivering safe patient care, teaching about individual communication styles is rare in nursing curricula. The Myers-Briggs Type Indicator (MBTI) was administered to 47 nursing students. Chi-square was used to analyze relationships between introversion/extroversion and gender. The data reported no significance relationships between introverts and extroverts and gender. The findings contribute to nursing education by bringing awareness of communication preference tools like the MBTI.


Relationship between the sonographic appearance of the thyroid and the clinical course and autoimmune activity of Graves' disease.
The aim of this study was to investigate the relationship between thyroid echogenicity and clinical course/immunologic parameters in Graves' disease. Two hundred and six outpatients with Graves' disease (31 men, 175 women; 46 +/- 23 years old) were studied with thyroid sonography and color Doppler sonography. Forty-five patients were treated for active hyperthyroidism, 161 were euthyroid (85 immediately before withdrawal of antithyroid drug at maintenance doses, 76 in stable remission after withdrawal of antithyroid treatment). Free triiodothyronine, free thyroxine, thyrotropin, and disease-specific autoantibodies (antithyrotropin-releasing hormone antibody) were determined in all patients. The ultrasound images were classified on the basis of homogeneous, finely unhomogeneous, or micronodular appearance. The proportion of unhomogeneous plus micronodular patterns was greater in hyperthyroid (77.8%) than in euthyroid patients (62.1%). In the latter group, the pattern distribution was significantly different in patients who were antibody positive relative to patients who were antibody negative (p < 0.01). In the stable remission subgroup, the pattern distribution differed according to thyrotropin levels (p < .01). There was a correlation between echopattern and color Doppler sonography as vascularization variables progressively increased in the transition from homogeneous to unhomogeneous and micronodular echopattern (most evident echotexture changes). A sonographic-based classification in Graves' disease can distinguish subgroups of patients with different clinical courses and disease activity. This procedure is easy to perform and correlates well with clinical findings.


Sub-inhibitory concentrations of some antibiotics can drive diversification of Pseudomonas aeruginosa populations in artificial sputum medium.
Pseudomonas aeruginosa populations within the cystic fibrosis lung exhibit extensive phenotypic and genetic diversification. The resultant population diversity is thought to be crucial to the persistence of infection and may underpin the progression of disease. However, because cystic fibrosis lungs represent ecologically complex and hostile environments, the selective forces driving this diversification in vivo remain unclear. We took an experimental evolution approach to test the hypothesis that sub-inhibitory antibiotics can drive diversification of P. aeruginosa populations. Replicate populations of P. aeruginosa LESB58 were cultured for seven days in artificial sputum medium with and without sub-inhibitory concentrations of various clinically relevant antibiotics. We then characterised diversification with respect to 13 phenotypic and genotypic characteristics. We observed that higher population diversity evolved in the presence of azithromycin, ceftazidime or colistin relative to antibiotic-free controls. Divergence occurred due to alterations in antimicrobial susceptibility profiles following exposure to azithromycin, ceftazidime and colistin. Alterations in colony morphology and pyocyanin production were observed following exposure to ceftazidime and colistin only. Diversification was not observed in the presence of meropenem. Our study indicates that certain antibiotics can promote population diversification when present in sub-inhibitory concentrations. Hence, the choice of antibiotic may have previously unforeseen implications for the development of P. aeruginosa infections in the lungs of cystic fibrosis patients.


Nondestructive experimental determination of bimaterial rectangular cantilever spring constants in water.
In order to address the issue of spring constant calibration in viscous fluids such as water, a new method is presented that allows for the experimental calibration of bimaterial cantilever spring constants. This method is based on modeling rectangular cantilever beam bending as a function of changing temperature. The temperature change is accomplished by heating water as it flows around the cantilever beams in an enclosed compartment. The optical static method of detection is used to measure the deflection of cantilever at the free end. Experimentally determined results are compared to Sader's method and to the Thermotune method most commonly used in cantilever calibrations. Results indicate that the new bimaterial thermal expansion method is accurate within 15%-20% of the actual cantilever spring constant, which is comparable to other nondestructive calibration techniques.


[Excessive stress damage of the lower extremity caused by sports. The value of sonographic diagnosis in stress damage of the lower extremity].
150 sportsmen with lesions and diseases of the lower extremity served as basis for demonstrating the possibilities offered by diagnosis via sonography. Main indications were articular and paraarticular diseases of the large joints (hip and knee) to demonstrate effusions, ganglia, bursae and tendon ruptures, diseases and injuries of the musculature at the thigh and lower leg, as well as the Achilles tendon with its various changes such as rupture, achillodynia and peritendinitis. Muscular and tendon ruptures can be differentiated via sonography in respect of extension, type, age and localisation. This makes differentiated treatment possible. Intraarticular lesions of the knee joint remain the domain of arthroscopy. Sonographic findings should always be supplemented by anamnesis, clinical findings and x-ray film so as not to overlook any bony injuries and damage of the capsular ligaments.


Detecting long-range correlations in time series of dorsal horn neuron discharges.
We have studied the discharge dynamics of dorsal horn neurons by applying the detrended fluctuation analysis and the wavelet transform technique. We have adopted that the neuronal discharge dynamics is manifested by the random time series of interspike intervals. In all cases studied, we found two different power-law type behaviors across interspike intervals enumeration scale, that are separated by crossover regions (which implies existence of two different types of neuronal noise). Our results reveal that complex neuronal dynamics may change in the presence of external stimulation, manifested by changing of the noise characteristics that appear before crossover.


Methotrexate for the treatment of unruptured tubal pregnancy: a prospective nonrandomized study.
The aim of this study was to compare in a prospective nonrandomized study, the efficacy of 2 methods of administering methotrexate (MTX) in the treatment of ectopic pregnancy (EP): transvaginal injection under sonographic control or intramuscular injection (IM). Patients with EP who met specific inclusion criteria for medical treatment were treated with MTX: 63 patients (group 1) were treated by IM and 47 patients (group 2) by transvaginal local injection. In group 1, 50 mg/m2 of MTX was injected intramuscularly; in group 2, transvaginal injection of 1 mg/kg of MTX was injected into the ectopic sac under sonographic control. When an additional dose of MTX was required, it was administrated IM at the dosage of 50 mg/m2 in both groups. The overall success rate, defined by a posttreatment normal hCG level (< 10 mUI/mL) was 71.4% in group 1 versus 91.5% in group 2 (P < 0.01); for patients with hCG levels < 2000 mUI/mL, 83% and 96%, respectively (not significant); for patients with hCG > or = 2000 mUI/mL, 37.5% and 86.4%, respectively (P < 0.01). In the medical treatment of EP, the efficacy of MTX is greater when administered by local transvaginal injection than by IM injection. We propose local treatment every time EP can be punctured, especially when hCG levels are > or = 2000 mUI/mL.


Necrotic hepatocellular carcinoma occurring within an inflammatory pseudotumor-like nodule.
Hepatocellular carcinoma (HCC) and inflammatory pseudotumor of the liver (IPL) are often difficult to differentiate before surgery. To date, colocalization of IPL and HCC has not been reported. We experienced a case of necrotic HCC surrounded by IPL-like tissue. The raised levels of alpha-fetoprotein and PIVKA-II declined to within the normal ranges after resection of the tumor. The IPL-like nodule most likely developed as a process of an inflammatory reaction such as abscess formation after the spontaneous destruction of the HCC. Our case is a warning that the presence of a 'pseudotumor' does not rule out the possible simultaneous presence of carcinoma.


Mechanochemical synthesis and characterisation of cocrystals and metal organic compounds.
The mechanochemical synthesis of two model compounds, a metal organic framework (H2Im)[Bi(1,4-bdc)2] (bdc = benzene dicarboxylate, H2Im = imidazole cation)) and a cocrystal (carbamazepine : indometacin 1 : 1) were followed ex situ using a combination of two analytical methods. Powder X-ray diffraction (XRD) and Raman spectroscopy data were evaluated for the synthesis of the metal organic framework. The XRD measurements and REM images were analysed for the synthesis of the cocrystal. The measurements revealed that both model compounds were synthesised within minutes. The metal organic framework (H2Im)[Bi(1,4-bdc)2] is synthesised via an intermediate structure. The cocrystal carbamazepine : indometacin 1 : 1 is formed within a few seconds. The crystallite size decreases during the further milling treatment.


Ruthenium-Catalyzed Hydrogenation of Carbocyclic Aromatic Amines: Access to Chiral Exocyclic Amines.
The first highly enantioselective hydrogenation of carbocyclic aromatic amines has been successfully realized using in situ-generated chiral ruthenium complex as catalyst, affording facile access to chiral exocyclic amines with up to 98% ee.


Lack of intracellular replication of M. tuberculosis and M. bovis BCG caused by delivering bacilli to lysosomes in murine brain microvascular endothelial cells.
Invasion and traversal of the blood-brain barrier (BBB) by Mycobacterium tuberculosis cause meningeal tuberculosis (TB) in the central nervous system (CNS). Meningeal TB is a serious, often fatal disease that disproportionately affects young children. The mechanisms involved in CNS invasion by M. tuberculosis bacilli are poorly understood. In this study, we microscopically examined endosomal trafficking and measured survival of M. tuberculosis and M. bovis Bacille Calmette-Guérin (BCG) bacilli in murine brain microvascular endothelial cells (BMECs). The results show that both species internalize but do not replicate in BMECs in the absence of a cytotoxic response. Confocal microscopy indicates that bacilli-containing vacuoles are associated with the early endosomal marker, Rab5, late endosomal marker, Rab7, and lysosomal marker, LAMP2, suggesting that bacilli-containing endosomes mature into endolysosomes in BMECs. Our data also show that a subset of intracellular M. tuberculosis, but not BCG bacilli, escape into the cytoplasm to avoid rapid lysosomal killing. However, the intracellular mycobacteria examined cannot spread cell-to-cell in BMECs. Taken together, these data show that with the exception of the small terminal cytoplasmic population of bacilli, M. tuberculosis does not modulate intracellular trafficking in BMECs as occurs in macrophages and lung epithelial and endothelial cells.


Mode-locking of a high power, 888 nm pumped Nd:YVO4 laser using nonlinear polarization rotation via Type I second harmonic generation.
Continuous-wave mode-locking of a laser exploiting the nonlinear polarization rotation (NPR) technique via Type I second harmonic generation is demonstrated for the first time. The NPR is generated by a lithium triborate crystal and transformed into nonlinear cavity losses of a 888 nm pumped Nd:YVO4 laser. Self-starting, reliable mode-locking has been achieved at a high average output power of 20.6 W and a pulse duration of 7.3 ps. Furthermore, transform limited pulses down to 2.7 ps have been demonstrated at 9.9 W.


Time-course transcriptome analysis of lungs from mice infected with inhaled aerosolized Stenotrophomonas maltophilia.
Stenotrophomonas maltophilia (SMA) has emerged as an important pathogen capable of causing an opportunistic and nosocomial infection. We performed RNA sequencing (RNA-seq) of lung tissues from mice with pulmonary SMA infection over time via aerosolized intratracheal inhalation to investigate transcription profile changes in SMA-infected lungs. A mouse model of acute lethal SMA pneumonia was established in this study using aerosolized intratracheal inhalation, laying the groundwork for future SMA research. RNA-seq was then used to create a transcriptional profile of the lungs of the model mice at 0, 4, 12, 24, 48, and 72 hours post-infection (hpi). Mfuzz time clustering, weighted gene coexpression network analysis (WGCNA), and Immune Cell Abundance Identifier for mouse (ImmuCellAI-mouse) were used to analyze RNA-seq data. A gradual change in the lung transcriptional profile was observed, which was consistent with the expected disease progression. At 4 hpi, the expression of genes related to the acute phase inflammatory response increased, as predicted abundance of innate immune cells. At this stage, an increased demand for energy was also observed, including an increase in the expression of genes involved in circulation, muscle function and mitochondrial respiratory chain function. The expression of genes associated with endoplasmic reticulum stress (ERS) and autophagy increased at 24 hpi. Unlike the number of natural killer (NK) cells following most bacterial lung infections, the abundance of NK cells decreased following infection with SMA. The expression levels of Cxcl10, Cd14, Gbp5, Cxcr2, Tnip1, Zc3h12a, Egr1, Sell and Gbp2 were high and previously unreported in SMA pneumonia, and they may be important targets for future studies. To our knowledge, this is the first study to investigate the pulmonary transcriptional response to SMA infection. The findings shed light on the molecular mechanisms underlying the pathogenesis of SMA pneumonia, which may aid in the development of therapies to reduce the occurrence of SMA pulmonary infection.


Cardiovascular sensory receptors and their regulatory mechanisms.
The role of cardiovascular receptors in the neural regulation of circulatory system is now well established. Atrial type B receptors located in the two atria and veno-atrial junctions, which are stimulated by atrial filling are believed to play an important role in the regulation of body fluid volume and heart rate. Heart rate is influenced also by other sensory receptors e.g. arterial baroreceptors, ventricular receptors, pulmonary stretch receptors and chemoreceptors. Of all these visceral receptors, arterial baroreceptors located mainly in the aortic arch and the carotid sinus region are stimulated by intravascular pressure; play a major role in the regulation of blood pressure by changes in heart rate and vascular tone. The vascular tone is also affected by the circulatory levels of various neurotransmitters and hormones. Vasodilatory response to adenosine and acetylcholine is partly mediated through endothelium-derived relaxing factors (EDRF), hyperpolarizing factors (EDHF) and contracting factors (EDCF). The endothelium-dependent mechanisms are altered during hypertension and diabetes. The autonomic control of blood pressure is primarily through arterial baroreceptors. The sensitivity of the baroreceptor heart rate reflex is significantly attenuated on occlusion of left anterior descending coronary artery (LAD) of anaesthetised dogs taken as an experimental model of coronary insufficiency in-patients of coronary heart disease. The fall in the sensitivity of baroreflex on LAD occlusion is mediated primarily by sympathetic limb of the autonomic nervous system. Acute fall in hemoglobin level by hemodilution in dogs produced an increase in cardiac output by increasing the heart rate through inhibition of parasympathetic tone. After parasympathetic blockade the increase in cardiac output on fall in hemoglobin was due to a rise in the stroke volume. Acute fall in hemoglobin level attenuated the baroreflex response. Sustained changes in blood pressure cause resetting of baroreflex i.e. increase in arterial pressure involves reduced activity of baroreceptors at equivalent pressure and vascular stretch. Like in acute hypoxia the altered responsiveness of baroreceptor heart rate reflex during oxygen deficiency due to acute occlusion of LAD or acute normovolemic hemodilution may involve both peripheral and central components and possibility of modulation by circulating hormones also exists.


Bacteria in Ostreococcus tauri cultures - friends, foes or hitchhikers?
Marine phytoplankton produce half of the oxygen we breathe and their astounding diversity is just starting to be unraveled. Many microbial phytoplankton are thought to be phototrophic, depending solely on inorganic sources of carbon and minerals for growth rather than preying on other planktonic cells. However, there is increasing evidence that symbiotic associations, to a large extent with bacteria, are required for vitamin or nutrient uptake for many eukaryotic microalgae. Here, we use in silico approaches to look for putative symbiotic interactions by analysing the gene content of microbial communities associated with 13 different Ostreococcus tauri (Chlorophyta, Mamilleophyceae) cultures sampled from the Mediterranean Sea. While we find evidence for bacteria in all cultures, there is no ubiquitous bacterial group, and the most prevalent group, Flavobacteria, is present in 10 out of 13 cultures. Among seven of the microbiomes, we detected genes predicted to encode type 3 secretion systems (T3SS, in 6/7 microbiomes) and/or putative type 6 secretion systems (T6SS, in 4/7 microbiomes). Phylogenetic analyses show that the corresponding genes are closely related to genes of systems identified in bacterial-plant interactions, suggesting that these T3SS might be involved in cell-to-cell interactions with O. tauri.


Pseudohyperkalemia due to cryohydrocytosis in GLUT1 deficiency syndrome. A case report and literature review.
Cryohydrocytosis is a form of stomatocytosis characterized by the leakage of sodium and potassium from red blood cells at low temperatures, characterized by pseudohyperkalemia. Stomatin-deficient cryohydrocytosis is an extremely rare variant that only recently has been related to pathogenic variants in the SLC2A1 gene, encoding the main glucose transporter of the blood-brain barrier and red blood cells, GLUT1. It follows that GLUT1 deficiency syndrome, a rare but significant cause of metabolic epilepsy, may present with stomatin-deficient cryohydrocytosis, although this correlation has only been reported in a few instances. We present the case of a patient carrying a novel de novo SLC2A1 pathogenic variant presenting with GLUT1 deficiency syndrome, pseudohyperkalemia, and splenomegaly consistent with cryohydrocytosis. We also review the previously reported cases of stomatin-deficient cryohydrocytosis in the literature. As highlighted by our case, elevated potassium levels are a cause of concern, and GLUT1 deficiency syndrome patients are thus at risk of being subjected to unnecessary examinations; pseudohyperkalemia may be underrecognized in clinical practice.


[Development of a colloidal gold immuno-chromatography assay to detect methamphetamine].
A rapid detector method for non-professional staff detecting methamphetamine in scene, no instrument, sensitivity and specificity, would be set up. Bagg albino C mice immunized with methamphetamine-modified bovine serum albumin were utilized for monoclonal antibody generation by the method of limited dilution technology. The detection of antibody typing kit was used for analysis the antibody subtype. Physical method was used for purified antibody labeled with colloidal gold. Colloidal gold test strip was composed and detected sensitivity and specificity. Seven special monoclonal antibodies were screened by limited dilution technology, among which valence of purified R6 antibody reached 10(8) via ciELISA, and belonged to IgG1 by the detection of antibody typing kit. Monoclonal antibody against methamphetamine labeling with colloidal gold particles was 5 microg/ml. The sensitivity of colloidal gold immuno-chromatography assay (GICA) for methamphetamine was 500 ng/ml. The cross-reactivity of the GICA detection card to eight analogs did not appear. GICA with high sensitivity, as a screening tool, may effectively contribute to Public Security Officers to detect narcotics in scene.


A 90-day oral exposure to food-grade gold at relevant human doses impacts the gut microbiota and the local immune system in a sex-dependent manner in mice.
Edible gold (Au) is commonly used as a food additive (E175 in EU) for confectionery and cake decorations, coatings and in beverages. Food-grade gold is most often composed of thin Au sheets or flakes exhibiting micro- and nanometric dimensions in their thickness. Concerns about the impact of mineral particles used as food additives on human health are increasing with respect to the particular physico-chemical properties of nanosized particles, which enable them to cross biological barriers and interact with various body cell compartments. In this study, male and female mice were exposed daily to E175 or an Au nanomaterial (Ref-Au) incorporated into food at relevant human dose for 90 days in order to determine the potential toxicity of edible gold. E175 or Ref-Au exposure in mice did not induce any histomorphological damage of the liver, spleen or intestine, nor any genotoxic effects in the colon and liver despite an apparent higher intestinal absorption level of Au particles in mice exposed to Ref-Au compared to the E175 food additive. No changes in the intestinal microbiota were reported after treatment with Ref-Au, regardless of sex. In contrast, after E175 exposure, an increase in the Firmicutes/Bacteroidetes ratio and in the abundance of Proteobacteria were observed in females, while a decrease in the production of short-chain fatty acids occurred in both sexes. Moreover, increased production of IL-6, TNFα and IL-1β was observed in the colon of female mice at the end of the 90-day exposure to E175, whereas, decreased IL-6, IL-1β, IL-17 and TGFβ levels were found in the male colon. These results revealed that a 90-day exposure to E175 added to the diet alters the gut microbiota and intestinal immune response in a sex-dependent manner in mice. Within the dose range of human exposure to E175, these alterations remained low in both sexes and mostly appeared to be nontoxic. However, at the higher dose, the observed gut dysbiosis and the intestinal low-grade inflammation in female mice could favour the occurrence of metabolic disorders supporting the establishment of toxic reference values for the safe use of gold as food additive.


Spectroscopic consideration of the surface potential built across phthalocyanine thin films on a metal electrode.
The nonlinear optical properties of tert-butyl phthalocyanine copper Langmuir-Blodgett (CuttbPc LB) films and vacuum-evaporated phthalocyanine copper (CuPc) films deposited on a metal surface were investigated by second-harmonic generation (SHG) spectroscopy. At the organic/metal interface, a space charge field is formed due to the presence of excess charge injected from a metal electrode to the organic layer. Since the Pc molecule has D4h symmetry, an inversion center is present and the optical SH process is not allowed under the electric-dipole approximation. However, the space charge field at the interface directly influences the symmetric structure of the electrons in the Pc molecule. We investigated the contributions of the surface potential to the SHG using Pc LB and vacuum-evaporated films deposited on aluminum (Al) and gold (Au) metal electrodes, where a distinctive difference in the spectrum for the Pc films on the Al and Au surfaces was observed. The contribution of the surface potential was revealed based on the resonant conditions of the SH process, taking into account the electric-quadrupole transition and dc-field-induced electric-dipole transition.