Endothelial thromboxane production plays a role in the contraction caused by 5-hydroxytryptamine in rat basilar arteries.
The goal of the present study was to characterize the role of the endothelium in the 5-hydroxytryptamine (5-HT)-induced contraction of the rat basilar artery. Rat basilar artery segments were mounted in myographs to study their isometric tension development. 5-HT caused dose-dependent contractions that were minimally affected by endothelium removal. The dose-response curve obtained with the 5-HT1 receptor agonist, 5-carboxamidotryptamine (5-CT), was biphasic in arteries with endothelium; removal of the endothelium eliminated the first phase of the contraction. The 5-HT2 receptor antagonist, ketanserin (30 nM), shifted the dose-response curve to 5-HT to the right; in arteries with endothelium, the curve became biphasic. Ketanserin inhibited the second phase of the dose-response curve to 5-CT. The mixed 5-HT1/5-HT2 receptor antagonist, metergoline (30 nM), shifted the dose-response curve to 5-HT non-competitively to the right and depressed both phases of the dose-response curve to 5-CT. In basilar arteries with endothelium and treated with ketanserin, the thromboxane A2 receptor antagonist, ICI 192605 (1 microM), significantly decreased the responsiveness to 5-HT and the dose-response curve for 5-HT became monophasic. ICI 192605 and the thromboxane A2 synthase inhibitor, ridogrel (10 microM), both suppressed the first phase of the dose-response curve to 5-CT. These data indicate that both endothelial 5-HT1 and smooth muscle 5-HT2 receptors participate in the contractions caused by 5-HT in the rat basilar artery.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of Theileria spp. in sheep and goats from Jeddah, Saudi Arabia, using molecular techniques.
Thileriosis is a tick -born disease caused by hemoprotozoan parasites which has global veterinary and economic implications. Blood samples were collected from 216 sheep and 83 goats from Jeddah, Saudi Arabia, were analyzed to determine whether the animals were infected with Theileria spp. parasites. The parasites were detected using a polymerase chain reaction (PCR) targeting the gene of 18S rRNA followed by sequencing. According to obtained findings, Theileria spp. were detected in sheep (57.8%, 48/83) and goats (51.9%, 112/216). Phylogenetic analysis to sequence data showed that T. ovis identified in this study were found to be closely connected to an isolate from Turkey, with 84.4-99.8% pairwise identity and 52.35-99.79% coverage.


Influence of the statistical significance of results and spin on readers' interpretation of the results in an abstract for a hypothetical clinical trial: a randomised trial.
To assess the impact on readers' interpretation of the results reported in an abstract for a hypothetical clinical trial with (1) a statistically significant result (SSR), (2) spin, (3) both an SSR and spin compared with (4) no spin and no SSR. Health students and professionals from universities and health institutions in France and the UK. Participants completed an online questionnaire using Likert scales and free text, after reading one of the four versions of an abstract about a hypothetical randomised trial evaluating 'Naranex' and 'Bulofil' (two hypothetical drugs) for chronic low back pain. The abstracts differed in (1) reported result of 'mean difference of 1.31 points (95% CI 0.08 to 2.54, p= 0.04)' or 'mean difference of 1.31 points (95% CI -0.08 to 2.70, p= 0.06)' and (2) presence or absence of spin. The effect size for the trial's primary outcome (pain disability score) was the same in each abstract, slightly in favour of Naranex. The reader's interpretation of the trial's results, based on their answer (1, disagree; 4, neutral; 7, agree) to the following statement: 'About the main findings of the study, what is your opinion about the following statement: 'Naranex is better than Bulofil'?' Two hundred and ninety-seven of the 404 people randomised to receive one of the four abstracts completed the study. Respondents were more likely to favour Narenex when the abstract reported an SSR without spin, a statistically significant result with spin, a non-statistically significant result with spin, compared with when it reported a non-SSR without spin. Statistical significance appears to have influenced readers' perception whatever the level of spin, while spin influenced readers' perception when the results were not statistically significant but did not appear to have an impact when results were statistically significant.


Highly efficient photodegradation of toxic organic pollutants using Cu-doped V2O5 nanosheets under visible light.
Photodegradation of organic pollutants using metal oxides has shown extraordinary promise owing to the catalytic efficacy, low cost, less noxiousness, and good chemical constancy. In this research, pure and transition metal ions (Cu)-doped V2O5 nanosheets were synthesized and investigated for their photocatalytic efficiency using methyl blue (MB) and rhodamine B (RhB) organic dye pollutants under visible light irradiation. The orthorhombic crystal phase was confirmed by XRD analysis, which exhibited a stable phase upon incorporating Cu dopant ions. Optical properties were examined using optical absorption spectroscopy, while a reduced band gap was observed in the doped V2O5 nanosheets over the undoped sample. EIS analysis confirmed lower charge resistance in doped V2O5 nanosheets. The Cu dopant incorporation into the host matrix considerably enhanced photodegradation efficiency for MB and RhB impurities under light illumination. The improvement in catalytic efficacy is attributed to dopant ions that can separate photoinduced charge carriers and the quick movement of the charge. Moreover, comparatively lesser crystalline size, improved specific surface area, and hydroxyl group onto the catalyst surface are quite advantageous to offer better photocatalytic activity of Cu-doped V2O5 nanosheets.


Pharmacokinetics of norethindrone acetate in women.
The plasma half-life, MCR and plasma metabolite levels at various time intervals have been studied in six women after an intravenous injection of 3H-norethindrone acetate. The disappearance curve due to norethindrone acetate showed an initial rapid disappearance of 3H with an average half-life of 7.5 minutes and a subsequent slow disapperance with a half-life of 51.5 hours. Norethindrone acetate was cleared from the plasma with an average MCR of 495 L/day. Norethindrone acetate is rapidly metabolised after an intravenous injection. Norethindrone, the main metabolite, disappears from the plasma with an average half-life of 34.8 hours. Norethindrone maintains a high level compared with norethindrone acetate at all time intervals up to 24 hours and an equilibrium is reached between the two at 24 to 48 hours.


Structure activity evaluation and computational analysis identify potent, novel 3-benzylidene chroman-4-one analogs with anti-fungal, anti-oxidant, and anti-cancer activities.
3-Benzylidene chroman-4-ones share close homology with naturally occurring bioactive compounds. This study evaluated the antifungal, antioxidant, and anticancer activities of novel 3-benzylidene chromanone analogs with respect to their structure-activity relationships. Compounds 45e-64e were synthesized inhouse. Aspergillus niger (MTCC 1344) Aspergillus flavus and Botrytis cinerea were the fungal strains tested. Computational docking analysis was carried out for vanin-1, estrogen receptor (ER), and Akt proteins using Auto-dock vina. Free radical scavenging and total antioxidant capacity was analyzed using spectrophotometric methods. MCF-7 (breast cancer) cell line was used for anticancer assays. Flow cytometry was used to detect cell cycle and apoptosis. Out of the twenty compounds screened, compounds 47e, 50e, 52e, 57e, and 61e that possessed either methoxy and ethoxy/methyl/isopropyl group exhibited very good activity against all fungi. Compounds possessing methoxy group alone showed moderate activity and compounds devoid of methoxy, and ethoxy groups did not show any activity. When computationally analyzed against target proteins for antioxidant properties, the compounds exhibited excellent binging efficacy to vanin-1 and ERs. These predictions were translated in the in vitro free-radical scavenging and antioxidant assays. The compounds exhibited anti-proliferative efficacy in breast cancer cell line, increased the sub-G0/G1 cell cycle populations and total apoptosis in MCF-7 cells. Additionally, the compounds also depicted excelling binging energy when computationally analyzed for Akt enzyme binding. In summary, our study identified potential analogs of 3-benzylidene chroman-4-one molecules with excellent anti-fungal, anti-oxidant, and anticancer activities which demand further research for drug developments.


Secular trends in first-time hospitalization for heart failure with following one-year readmission and mortality rates in the 3.8 million adult population of Silesia, Poland between 2010 and 2016. The SILCARD database.
Heart failure (HF) continues to be an important medical and social problem, with high morbidity and mortality. Data on the trends in hospitalizations, hospital readmissions and mortality is of great importance both from the epidemiological and clinical points of view. We analyzed the secular trends in first-time hospital admissions for heart failure between 2010 and 2016, derived from SILCARD database, covering a population of 3.8 million adults. Patient characteristics as well as data on in-hospital and 12-month outcomes were recorded for each year. The total number of first-time hospitalizations for HF as the primary diagnosis showed a downward trend during the study period (reduction by 12%, p = 0.07), with a constant patient age (mean 74.3 ± 11.3 years). The length of hospital stay shortened from 10.9 to 9.6 days (p = 0.003). Crude in-hospital mortality remained constant at around 14% (p = 0.55), but after adjustment for sex and age, mortality rates tended to decrease from 17.2% in 2010 to 11.5% in 2016 (p = 0.007). All-cause hospital readmission rates in 12-month follow-up increased which was due to non-CV hospitalizations, since both CV- and HF-related readmissions were constant throughout the years. Crude 12-month mortality was constant, but after adjustment for age and sex absolute reduction by about 10% was found (p = 0.02). Despite the decreasing duration of hospital stay, significant improvement in both in-hospital and long-term survival was observed, with constant rates of hospital readmissions related to HF.


Brazilian version of the Mattis dementia rating scale: diagnosis of mild dementia in Alzheimer's disease.
To verify the diagnostic accuracy of the Brazilian version of the Mattis Dementia Rating Scale (DRS) in the diagnosis of patients with mild dementia in Alzheimer's disease (AD); to verify the interference of the variables age and schooling on the performance of the DRS. The DRS was administered to 41 patients with mild AD and to 60 controls. In order to analyze the effects of age and schooling on the performance of the tests, patients and controls were separated into three age groups and three levels of schooling. The cutoff score of 122 showed a sensitivity of 91.7 % and specificity of 87.8 %. Age and schooling interfered in the DRS total score and in the scores of its subscales. The DRS showed good diagnostic accuracy in the discrimination of patients with mild AD from the control individuals. In the sample examined, the effects of schooling were more marked than age.


Association of maternity formula supplementation during pregnancy with small for gestational age birth in Chinese newborns.
This study aimed to explore the association between maternity formula supplementation and small for gestational age (SGA) status in Chinese newborns. Data were from a population-based cross-sectional survey conducted in Shaanxi, Northwest China between August and December 2013. A total of 27 780 women pregnant with singletons and 356 with twins were included in this survey. Information on use of maternity formulas fortified with vitamins, folic acid, pantothenic acid, calcium, iron, zinc, and docosahexaenoic acid (DHA) was collected. SGA was defined as birthweight <10th percentile of fetal growth. Generalized linear models and estimating equation models were used to estimate crude odds ratios (ORs) or adjusted ORs with 95% confidence intervals (CIs) for SGA. The rate of maternity formula supplementation during the entire pregnancy was 13.0% in the overall population. There was no significant association between maternal formula supplementation during pregnancy and the risk of total SGA birth (OR: 1.00; 95% CI, 0.90-1.11; P = 0.950). However, maternity formula supplementation during pregnancy was related to a lower risk of SGA for twins (OR: 0.49; 95% CI, 0.31-0.80; P = 0.004), twin A (OR: 0.50; 95% CI, 0.25-0.98; P = 0.045), and twin B (OR: 0.48; 95% CI, 0.25-0.95; P = 0.034). Furthermore, maternity formula supplementation during the first trimester was inversely associated with the risk of SGA birth of twins (OR: 0.32; 95% CI, 0.15-0.65; P = 0.002). No significant association was observed between maternity formula supplementation and total SGA birth. However, women supplemented with maternal formula during pregnancy, especially during the first trimester, may have a reduced risk of SGA birth of twins.


Macular dystrophy associated with the A3243G mitochondrial DNA mutation. Distinct retinal and associated features, disease variability, and characterization of asymptomatic family members.
To determine (1) detailed retinal and audiological features of probands harboring the A3243G mitochondrial DNA mutation (m.3243A>G) and their asymptomatic maternal relatives, (2) intrafamilial and interfamilial phenotypic variability, and (3) the presence of other systemic features. Seven probands harboring the A3243G mitochondrial DNA mutation and 36 asymptomatic maternal relatives were ascertained. Participants underwent ophthalmologic examination, fundus photography, autofluorescence imaging, and audiological evaluation and completed a questionnaire. Blood samples were taken to test for diabetes, determine renal function, and screen relatives for the A3243G mutation. The A3243G mutation was associated with both intrafamilial and interfamilial variable expressivity regarding retinal appearance, hearing loss, diabetes, and other systemic features. The most common macular appearance in maternal relatives (one-third of those positive for the mutation) was mild abnormalities of the retinal pigment epithelium (more clearly identified using autofluorescence), which may therefore be a useful clinical indicator suggesting positive mutation status. Four probands and 13 mutation-positive relatives were found to have evidence of significant bilateral, cochlear, symmetrical age-adjusted hearing loss, predominantly affecting high frequencies. Hearing loss and macular disturbance were the most frequent findings in mutation-positive participants, with 95% of mutation-positive relatives having hearing loss. Diabetes was the least frequent finding. Patients with progressive hearing loss may merit ophthalmologic assessment to detect retinal abnormalities consistent with the A3243G mutation. Conversely, patients with macular features in keeping with the A3243G mutation should have audiological testing, even in the absence of diabetes or a positive family history.


Wood profiling by non-targeted liquid chromatography high-resolution mass spectrometry: Part 2, Detection of the geographical origin of spruce wood (Picea abies) by determination of metabolite pattern.
A non-targeted metabolomics-based approach using liquid chromatography high-resolution mass spectrometry was used to authenticate spruce wood (Picea abies) from two geographic source areas. The two sample sites were located in Germany and only 250 km apart. In order to achieve the highest possible metabolite coverage, the spruces samples were measured with four different methods using liquid chromatography high-resolution mass spectrometry. In this way, a total of approximately 4,100 features were detected, which included non-polar, polar, and intermediate-polar metabolites. Using supervised multivariate methods, a distinction between the two sample groups could be achieved on the basis of non-polar data sets. The major metabolites contributing to differentiation were identified by MS/MS experiments and were from the following classes of compounds: ceramides, fatty acids, glycerolipids, and phytosterols. Based on the soil descriptions of the two sites, it was concluded that there is probably a close relationship between nutrient availability and the differences in concentration of the marker compounds. The results show that a metabolomics-based approach is also suitable for differentiation of origin, even if the sample sites are close to each other.


Early Experience with the New Ovation Alto Stent Graft in Endovascular Abdominal Aortic Aneurysm Repair.
Since 2010, the Ovation Abdominal Stent Graft System has offered a new sealing concept, achieved by a sealing ring filled with polymer 13 mm from the renal arteries. In the latest version, called Ovation Alto, the sealing ring is relocated 6 mm closer to the top of the fabric. This study describes the early clinical outcomes, after CE Mark approval in August 2020, of endovascular aneurysm repair with the Alto endograft. Eleven patients underwent endovascular aneurysm repair with implantation of Ovation Alto endografts. All patients were male, and the median age was 75 (IQR 5.5) years. Hostile proximal aortic neck (<10 mm) was identified in six cases (54.5%). All procedures were performed using bilateral percutaneous approaches with no groin complications. The median procedure time was 58 (IQR 7.2) minutes, the median contrast volume used was 65 (IQR 4.2) mL, and the median blood loss 40 (IQR 12.4) mL. Technical success was achieved in all cases. The median stent graft landing distance between the top of the fabric and the lowest renal artery was 1.4 (IQR 0.8) mm. No intra-operative high flow endoleaks were registered. At one and six month follow up, there was 100% clinical success (no type I/III endoleak, sac enlargement, stent graft migration, polymer leakage, abdominal aortic aneurysm related mortality, or secondary intervention). Initial experience confirms the early technical and clinical success of the new Ovation Alto stent graft. Technical modifications to the endograft could allow for accommodation of a more comprehensive range of anatomies on label. Further studies are needed to evaluate long term durability outcomes.


Genetic screening of an endemic mutation in the DYSF gene in an isolated, mountainous population in the Republic of Dagestan.
Dysferlinopathy has a high prevalence in relatively isolated ethnic groups where consanguineous marriages are characteristic and/or the founder effect exists. However, the frequency of endemic mutations in most isolates has not been investigated. The prevalence of the pathological DYSF gene variant (NM_003494.4); c.200_201delinsAT, p. Val67Asp (rs121908957) was investigated in an isolated Avar population in the Republic of Dagestan. Genetic screenings were conducted in a remote mountainous region characterized by a high level of consanguinity among its inhabitants. In total, 746 individuals were included in the screenings. This pathological DYSF gene variant causes two primary phenotypes of dysferlinopathy: limb-girdle muscular dystrophy (LGMD) type R2 and Miyoshi muscular dystrophy type 1. Results indicated a high prevalence of the allele at 14% (95% confidence interval [CI]: 12-17; 138 out of 1518 alleles), while the allele in the homozygous state was detected in 29 cases-3.8% (CI: 2.6-5.4). The population load for dysferlinopathy was 832.3 ± 153.9 per 100,000 with an average prevalence of limb-girdle muscular dystrophies ranging from 0.38 ± 0.38 to 5.93 ± 1.44 per 100,000. A significant burden of the allele was due to inbreeding, as evidenced by a deficiency of heterozygotes and the Wright fixation index equal to 0.14 (CI 0.06-0.23).


Thy-1 epitopes are expressed on murine myeloid leukemia and reticulum sarcoma cells.
Expression of Thy-1.2 specificities in cells from 29 primary spontaneous leukemias of random-bred ICR Swiss mice was examined by cell membrane and cytoplasmic immunofluorescence with monoclonal HO-13-4 antibody [1]. The Thy-1.2 epitopes were detected in all thymic lymphomas and were absent in the lymphomas of non-thymic origin. Unexpectedly, the Thy-1.2 epitopes were also detected in 71% (5/7) of myeloid leukemias and 40% (4/10) of reticulum cell sarcomas examined.


Identification of Glu173 as the critical amino acid residue for the ADP-ribosyltransferase activity of Clostridium botulinum C3 exoenzyme.
Clostridium botulinum C3 exoenzyme specifically ADP-ribosylates rho-p21 in eukaryotic cells. Trp18 and Glu173 of this enzyme were substituted with other amino acids via site-directed mutagenesis. All substitutions at Glu173 caused a significant reduction in affinity for NAD and diminished ADP-ribosyltransferase activity. On the other hand, the activity of enzymes with the substitution at Trp18 remained intact. Swiss 3T3 cells treated with the enzyme with the Trp18 substitution showed the typical morphologic changes of the C3 exoenzyme phenotype. In contrast, no changes were found in cells incubated with the Glu173-substituted enzyme. These results indicate that the Glu173 residue of the C3 exoenzyme plays a key role in interacting with NAD and in expression of ADP-ribosyltransferase activity, which is essential for the phenotypic change by C3 exoenzyme treatment.


The cost-effectiveness of screening the U.S. blood supply for West Nile virus.
The spread of West Nile virus across North America and evidence of transmission by transfusion prompted the U.S. Food and Drug Administration to encourage the development of methods to screen the blood supply. To assess the cost-effectiveness of nucleic acid amplification testing for West Nile virus in the U.S. blood supply. Markov cohort simulation. Outcome probabilities estimated from nucleic acid testing done for West Nile virus in 2003, data from the Centers for Disease Control and Prevention, and published literature. Costs were taken from an economic study of West Nile virus infection and from estimated test costs. TARGET POPULATIONS: Transfusion recipients, 60 years of age or older, with and without underlying immunocompromise. Lifetime. Societal. The authors compared 6 strategies, taking into consideration minipool (pools of 6 to 16 donations) versus individual donation testing, and the geographic and seasonal nature of West Nile virus activity. Costs and effects of each strategy based on the prevention of transfusion-transmitted West Nile virus. The cost-effectiveness of annual, national minipool testing was 483,000 dollars per quality-adjusted life-year (QALY), whereas the cost-effectiveness of annual, national individual donation testing was 897,000 dollars/QALY. The cost-effectiveness of targeted individual donation testing in an area experiencing an outbreak coupled with minipool testing elsewhere was 520,000 dollars/QALY. In 1-way analyses, the most important influences were the prevalence of West Nile virus and the cost of minipool testing and individual donation testing. The 95% range of results from probabilistic sensitivity analysis for targeted individual donation testing was 256,000 dollars to 1,044,000 dollars/QALY. The outcomes of West Nile virus infection were based on data from the general population rather than from the population who received transfusions. The results are most useful in the context of geographically focused outbreaks of West Nile virus infection. Using targeted individual donation testing to interdict blood donations that are positive for the West Nile virus is relatively cost-effective but is highly dependent on West Nile virus prevalence.


Role of Rho-ROCK signaling in MOLT4 cells metastasis induced by CCL25.
Our previous research has revealed that binding of the chemokine CCL25 to the CCR9 provides chemotactic cues guiding leukemic cells to specific tissues and organs. The RhoA-ROCK pathway might be involved in cancer migration. The purpose of this study was to explore the role of the RhoA-ROCK-MLC axis in leukemic cell migration following exposure to CCL25. The results showed that CCL25 could increase the amount of the GTPase RhoA and activate MLC in MOLT4 cells in a time-dependent manner. C3 exoenzyme and Y-27632 could block MOLT4 cell migration and chemotaxis. Thus, the RhoA-ROCK-MLC axis might play an important role in MOLT4 cell metastasis induced by CCL25.


Increased aryl hydrocarbon hydroxylase and prolyl hydroxylase activities in lung organ cultures exposed to benzo[a]pyrene.
Exposure of neo-natal rat lungs in organ culture to 10--25 microM benzo[a]pyrene (BaP) elevated the activities of aryl hydrocarbon hydroxylase (AHH) and prolyl hydroxylase (PH). Pyrene, a non-carcinogenic hydrocarbon did not elicit this response. Prolyl hydroxylase is an indicator of collagen synthesis and increased PH activity in the lungs reflects increased collagen synthesis. Our studies suggest that the earliest events in BaP-induced lung injury may include altered collagen metabolism.


Towards a standardized informed consent procedure for live donor nephrectomy: What do surgeons tell their donors?
Living kidney donors comprise a unique group of "patients", undergoing an operation for the benefit of others. The informed consent process is therefore valued differently. Although this is a team effort, the surgeon is responsible for performing the donor nephrectomy, and often the one held accountable, should adverse events occur. Although there is some consensus on how the informed consent procedure should be arranged, practices vary. The aim of this study was to evaluate the surgical informed consent procedure for live donor nephrectomy, with special regards to disclosure of complications. A web-based survey was sent to all kidney transplant surgeons (n = 50) in eight transplant centers with questions regarding the local procedure and disclosure of specific details. Response rate was 98% (n = 49), of which 32 (65%) were involved in living donor education; overall, transplant- (50%), vascular- (31%), and abdominal surgeons (13%), and urologists (6%) performed donor nephrectomies in the eight centers. Informed consent procedures varied, ranging from assumed to signed consent. Bleeding was the only complication every surgeon mentioned. Risk of death was always mentioned by 16 surgeons (50%), sometimes by 13 (41%), three surgeons (9%) never disclosed this disastrous complication. Reported mortality rates ranged from 0.003% to 0.1%. Mentioning frequencies for all other complications varied. Important complications are not always disclosed during the surgical informed consent process for live donor nephrectomy. Informed consent procedures vary. To optimally prepare living kidney donors for the procedure, a standardized informed consent procedure for live donor nephrectomy is highly recommended.


Immobilized laccase mediated dye decolorization and transformation pathway of azo dye acid red 27.
Laccases have good potential as bioremediating agents and can be used continuously in the immobilized form like many other enzymes. In the present study, laccase from Cyathus bulleri was immobilized by entrapment in Poly Vinyl Alcohol (PVA) beads cross-linked with either nitrate or boric acid. Immobilized laccase was used for dye decolorization in both batch and continuous mode employing a packed bed column. The products of degradation of dye Acid Red 27 were identified by LC MS/MS analysis. The method led to very effective (90%) laccase immobilization and also imparted significant stability to the enzyme (more than 70% after 5 months of storage at 4°C). In batch decolorization, 90-95% decolorization was achieved of the simulated dye effluent for up to 10-20 cycles. Continuous decolorization in a packed bed bioreactor led to nearly 90% decolorization for up to 5 days. The immobilized laccase was also effective in decolorization and degradation of Acid Red 27 in the presence of a mediator. Four products of degradation were identified by LC-MS/MS analysis. The immobilized laccase in PVA-nitrate was concluded to be an effective agent in treatment of textile dye effluents.


Study of Insulin-Loaded Chitosan Nanoparticle Effects on TGF-β1 and Fibronectin Expression in Kidney Tissue of Type 1 Diabetic Rats.
In diabetes, the increasing blood glucose levels through oxidative stress, with increase in inflammatory cytokines and growth factors, such as TGF-β1, can cause long-term complications, including nephropathy. Subcutaneous injection of insulin is a common method used to treat Type 1 diabetes, which can lead to problems such as hypoglycemia and edema. In the present study, we examined the effect of insulin in its two injectable and oral forms on the expression of TGF-β1 and fibronectin in kidney tissue of STZ diabetic rats. A total of 25 male Wistar rats were randomly divided into 5 groups: C: normal control, D: diabetic control, D+NP, oral insulin-loaded trimethyl chitosan nanoparticles (8 IU/kg), and subcutaneously injected insulin (8 IU/kg). The groups were treated from 8th to 10th weeks. After 10 weeks, FBS was measured. Also, the TGF-β1 and fibronectin mRNA expression and serum TGF-β1 protein were examined in the kidney tissue. Structural changes in the kidney tissue were studied using H&E staining. After 10 weeks of diabetes induction, the rats showed significant change in blood glucose, weight, serum TGF-β1, Fibronectin and TGF-β1 expression of kidney in diabetic groups (p < 0.05). Oral insulin-loaded trimethyl chitosan nanoparticles treatment, similar to injected insulin, significantly ameliorate blood glucose and rats' weight (p < 0.05). However, the reduction in fibronectin and TGF-β1 expression and serum TGF-β1 protein by both treatments was not statistically significant (p > 0.05). These data showed that oral insulin-loaded trimethyl chitosan nanoparticles were better therapeutic intervention than injected insulin for Type 1 diabetes.


Predominant association of adenovirus type 12 DNA with human chromosome 1 early in productive infection.
In human KB cells productively infected with human adenovirus type 12 (Ad12), viral DNA can recombine with cellular DNA. The functional significance of this covalent linkage is not understood. It is, however, conceivable that very early in the infection cycle integrated viral genes gain an advantage by being transcribed more effectively. In the present study, it has been shown that Ad12 DNA is associated predominantly with human chromosome number 1 and one chromosome in the CII group. This association has been detected as early as 2 hr after infection by in situ hybridization. Further work will be directed toward the analysis of viral transcription products within the first 2 hr of the infection cycle.


Field evaluation of Cd and Zn phytoextraction potential by the hyperaccumulators Thlaspi caerulescens and Arabidopsis halleri.
Field trials were undertaken to investigate the effect of the application of metal mobilizing agents, different sowing strategies and length of growing season on the extraction of Cd and Zn from soils by Thlaspi caerulescens and Arabidopsis halleri. None of the mobilizing agents used enhanced metal accumulation by T. caerulescens. Between 1998 and 2000, on average across plots where Cd or Zn exceeded allowable limits, T. caerulescens removed 1.3 and 0.3% of the total soil Cd and Zn. In one season when T. caerulescens was grown for 14 months, 21.7 and 4.4% of the total soil Cd and Zn was removed. This was larger than values found when T. caerulescens was grown for 4 months. A. halleri accumulated similar concentrations of Zn, but lower Cd concentrations than T. caerulescens. The results indicate that metal phytoextraction using T. caerulescens can be used to clean up soils moderately contaminated by Cd.


Prevention of perioperative vascular prosthetic infection with a novel triple antimicrobial-bonded arterial graft.
Previously, we investigated a locally developed technique of bonding arterial grafts with three antimicrobials to protect against early (within 2 weeks) perioperative bacterial contamination encountered occasionally during aortic graft prosthetic reconstruction. Vascular graft infections are classified by their appearance time (early [<4 months] vs late [>4 months] after graft implantation), degree of incorporation into the surrounding vessel wall, connectivity to the postoperative wound, and extent of graft involvement. In the current phase of testing, we evaluated the ability of our novel triple antimicrobial-bonded graft to prevent infection in the first 8 weeks after implantation. In nine Sinclair miniature pigs, we surgically implanted a 6-mm vascular Dacron patch graft in the infrarenal abdominal aorta. Five pigs received grafts chemically bonded with a 60-mg/mL solution of rifampin, minocycline, and chlorhexidine, and four pigs received unbonded grafts. Before implantation, the five bonded grafts and three of the unbonded grafts were immersed for 15 minutes in a 2-mL solution containing 1-2 × 107 colony-forming units (CFUs)/mL of Staphylococcus aureus (ATCC 29213); the fourth unbonded graft served as a control. At week 9, all of the grafts were explanted. All S aureus-inoculated bonded grafts (n = 5) showed no bacterial growth. The unbonded, uninoculated graft (n = 1) showed low-level bacterial growth (<1.2 × 103 CFUs); S cohnii spp urealyticus, but not S aureus, was isolated, which suggested accidental direct perioperative contamination. Two pigs that received S aureus-inoculated, unbonded grafts were euthanized because of severe S aureus infection (<6.56 × 108 CFUs per graft). Results of histopathologic analysis were concordant with the microbiologic findings. Most intergroup differences were observed in the inflammatory infiltrate in the aortic wall at the site of graft implantation. In all pigs that received bonded grafts, Gram staining showed no bacteria. Our triple-bonded aortic graft prevented perioperative aortic graft infection for at least 8 weeks in a porcine model. The synergistic antimicrobial activity of this graft was sufficient to prevent and/or eradicate infection during that period. Further studies are needed to assess the graft's ability to combat early-onset vascular graft infection for up to 4 months.


Evidence of ochratoxin A-detoxification activity of rumen fluid, intestinal fluid and soil samples as well as isolation of relevant microorganisms from these environments.
Dietary ochratoxin A (OTA) has a negative impact on performance of chickens and pigs. To avoid losses in animal production through intake of this mycotoxin and to prevent carry over to humans, strategies for counteracting have to be developed. In contrast to physical and chemical detoxification methods inactivation of ochratoxins by enzymatic reactions represent a very specific and gentle process. For the development of a new feed additive various environments have been screened for microorganisms with the capability of degrading or of cleaving the phenylalanine-moiety of ochratoxin A. Two OTA-degrading bacterial strains were isolated from rumen fluid and four pure cultures capable of cleaving ochratoxin A were obtained from pig intestine. The highest number of ochratoxin A degrading strains were found amongst aerobic bacteria which have mainly been isolated from soil.


Impact of podiatry resident experience level in hallux valgus surgery on postoperative outcomes.
Despite modern advancements in transosseous fixation and operative technique, hallux valgus (i.e., bunion) surgery is still associated with a higher than usual amount of patient dissatisfaction and is generally recognized as a complex and nuanced procedure requiring precise osseous and capsulotendon balancing. It stands to reason then that familiarity and skill level of trainee surgeons might impact surgical outcomes in this surgery. The aim of this study was to determine whether podiatry resident experience level influences midterm outcomes in hallux valgus surgery (HVS). Consecutive adults who underwent isolated HVS via distal metatarsal osteotomy at a single US metropolitan teaching hospital from January 2004 to January 2009 were contacted and asked to complete a validated outcome measure of foot health (Manchester-Oxford Foot Questionnaire) regarding their operated foot. Resident experience level was quantified using the surgical logs for the primary resident of record at the time of each case. Associations were assessed using linear and logistic regression analyses. A total of 102 adult patients (n = 102 feet) agreed to participate with a mean age of 46.8 years (standard deviation 13.1, range 18-71) and average length of follow-up 6.2 y (standard deviation 1.4, range 3.6-8.6). Level of trainee experience was not associated with postoperative outcomes in either the univariate (odds ratio 0.99 [95% confidence interval, 0.98-1.01], P = 0.827) or multivariate analyses (odds ratio 1.00 [95% confidence interval, 0.97-1.02], P = 0.907). We conclude that podiatry resident level of experience in HVS does not contribute appreciably to postoperative clinical outcomes.


Massage therapy utilisation by Australian women: Prevalence and determinants.
Massage is a popular form of health care used among women, yet little is known about the characteristics of women who use massage therapy and the rationale for its use. This study reports the prevalence and characteristics of young and middle-aged Australian women who consulted a massage therapist. The study analysed data from the Australian Longitudinal Study on Women's Health; a nationally-representative sample of Australian women. The data from 7,993 young, and 9,102 middle-aged women were included in the analyses and massage use was compared against measures of health status, health care utilisation, and demographics. Prevalence of consultation with a massage therapist in the previous 12 months was 42.4% in young women and 25.2% in middle-aged women. Women who consulted a massage therapist were more likely to consult other complementary medicine practitioners and/or use self-prescribed complementary medicine. Both young and middle-aged women were more likely to consult a massage therapist if they experienced musculoskeletal problems; however less likely, with chronic disease such as diabetes and hypertension. Despite large numbers of young and middle-aged Australian women consulting a massage therapist, no Australian studies investigate the prevalence of massage consultations and report correlations with characteristics relevant to demographic, health status and health service data. Our findings highlight the need for further investigation of women's choices relevant to the use of massage therapy. Such research could shape the future of women's health care by providing insight into women's decision making around massage therapy, conventional treatment and healthcare utilisation.


MicroRNA profile analysis of human prostate cancers.
We examined the microRNA (miRNA) expression profile of 40 prostatectomy specimens from stage T2a/b, early relapse and non-relapse cancer patients, to better understand the relationship between miRNA dysregulation and prostate oncogenesis. Paired analysis was carried out with microdissected, malignant and non-involved areas of each specimen, using high-throughput liquid-phase hybridization (mirMASA) reactions and 114 miRNA probes. Five miRNAs (miR-23b, -100, -145, -221 and -222) were significantly downregulated in malignant tissues, according to significance analysis of microarrays and paired t-test with Bonferroni correction. Lowered expression of miR-23b, -145, -221 and -222 in malignant tissues was validated by quantitative reverse transcription (qRT)-PCR analyses. Ectopic expression of these miRNAs significantly reduced LNCaP cancer cell growth, suggesting growth modulatory roles for these miRNAs. Patient subset analysis showed that those with post-surgery elevation of prostate-specific antigen (chemical relapse) displayed a distinct expression profile of 16 miRNAs, as compared with patients with non-relapse disease. A trend of increased expression (>40%) of miR-135b and miR-194 was observed by qRT-PCR confirmatory analysis of 11 patients from each clinical subset. These findings indicate that an altered miRNA expression signature accompanied the prostate oncogenic process. Additional, aberrant miRNA expression features may reflect a tendency for early disease relapse. Growth inhibition through the reconstitution of miRNAs is potentially applicable for experimental therapy of prostate cancer, pending molecular validation of targeted genes.


Amino acids in urine and plasma of urolithiasis patients.
Urine and plasma amino acids in healthy males and patients with calcium stones, were analyzed for thirty-four amino acids. There was no difference in urinary excretion of thirty-two amino acids between the two groups. Plasma values of taurine, aspartic acid, hydroxyproline, glutamic acid, glycine, alanine, cystathionine, ornithine and lysine were significantly higher in controls than in stone formers. Of these amino acids, aspartic acid, glutamic acid, glycine, alanine and lysine are the main amino acids of matrix protein in renal stones. The levels of aspartic acid, glutamic acid, glycine, alanine and lysine in the serum of normal individuals were higher than those in plasma. On the basis of the findings, these amino acids may form soluble complexes with calcium and heparin in stone formers. It is also possible that some amino acids act as promoters or inhibitors in the pathogenesis of calcium oxalate stones.


Data requirements for protein identification using chemically-assisted fragmentation and tandem mass spectrometry.
Many laboratories identify proteins by searching tandem mass spectrometry data against genomic or protein sequence databases. These database searches typically use the measured peptide masses or the derived peptide sequence and, in this paper, we focus on the latter. We study the minimum peptide sequence data requirements for definitive protein identification from protein sequence databases. Accurate mass measurements are not needed for definitive protein identification, even when a limited amount of sequence data is available for searching. This information has implications for the mass spectrometry performance (and cost), data base search strategies and proteomics research.


The palliative performance scale: examining its inter-rater reliability in an outpatient palliative radiation oncology clinic.
The Palliative Performance Scale (PPS) was developed by the Victoria Hospice Society in 1996 to modernize the Karnofsky Performance Scale. Currently, it is being used to measure palliative patient performance status in a variety of settings. Despite its widespread use, only one study has examined the inter-rater reliability of the PPS. To examine the inter-rater reliability of the PPS in measuring performance status in patients seen in an outpatient palliative radiation oncology clinic Performance status for 102 consecutive patients was assessed by an oncologist (MD), a radiation therapist (RT), and a research assistant (RA) in the Rapid Response Radiotherapy Program at the Odette Cancer Centre in Toronto, Ontario, Canada. Raters' scores were analyzed for correlation and compared to evaluate the inter-rater reliability of the PPS tool. Excellent correlation was found between the scores rated by the MD and RA (r = 0.86); good correlation was observed between scores rated by the MD and RT (r = 0.69) and the RT and RA (r = 0.77). Scores between all three raters, as well as between rater pairs, were also found to have good reliability as measured by the Chronbach's alpha coefficient. Significant results were obtained for the range of PPS scores in which the majority of our patients fell: 40-80%. PPS was shown to have good overall inter-rater reliability in an outpatient palliative setting, but more research is needed to establish the validity and reliability of the tool in a variety of different palliative settings.


Mixed-species association and a record of a hybrid offspring between Trachypithecus pileatus and Trachypithecus phayrei in Bangladesh.
The term mixed-species association has a broad range of definitions, from temporary foraging association to permanent group living. A mixed-species association mostly involves species from closely related taxa and is found in birds, mammals and fish. It ranges from passive association with little interaction to coordinated behavioural interactions between the group members of a mixed-species group. Mixed-species association can result in the production of hybrid offspring in the wild. In this study, we present, to the best of our knowledge, the first observational evidence of mixed-species association between the two threatened primate species Phayre's langur (Trachypithecus pileatus) and capped langur (Trachypithecus phayrei), in fragmented forest patches of northeast Bangladesh. We also report a presumed hybrid offspring between these species. We conducted a short-term study from December 2021 to April 2022 in three forest patches based on information from eco-tourism guides. We confirmed the presence of three mixed-species troops; in two of the groups an adult male T. phayrei had permanently immigrated into a group of T. pileatus, and in the other one an adult male T. pileatus had permanently immigrated into a group of T. phayrei. A long-term detailed study is needed to elucidate the reasons for these mixed-species associations, their behavioural patterns, the fate of the presumed hybrid offspring, and to understand the genetic relatedness between the individuals.


Novel therapies for Helicobacter pylori infection.
Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection. To evaluate orally administered novel therapies for the treatment of H. pylori infection. Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2-3Galb1-4Glc-(3'-sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present. None of the novel therapies appeared effective and no adverse events occurred. Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.


Nitric oxide modulates interleukin-2-induced proliferation in CTLL-2 cells.
The role of the L-arginine-nitric oxide metabolic pathway was explored for interleukin-2-induced proliferation in the cytotoxic T lymphocyte clone CTLL-2. Specific inhibition of nitric oxide synthase significantly diminished, in a concentration-dependent manner, (3)H-thymidine uptake of CTLL-2 cells in response to different concentrations of interleukin 2. Withdrawal of L-arginine from culture medium resulted as potent as the higher inhibition obtained when blocking nitric oxide synthase with L-arginine analogues. Furthermore, intermedial concentrations of Larginine and exogenous nitric oxide donors were found for achieving optimal IL2-induced proliferation of CTLL-2. These findings prompted us to suggest that intra- and/or inter-cellular nitric oxide signalling may contribute to the modulation of the IL2 mitogenic effect upon cytotoxic T lymphocytes.


Host habitat finding and host selection of theDrosophila parasitoidLeptopilina australis (Hymenoptera, Eucoilidae), with a comparison of the niches of EuropeanLeptopilina species.
Decaying petioles of giant hogweed,Heracleum mantegazzianum Sommier & Levier, are used as a breeding site by six species ofDrosophila and the drosophilidScaptomyza pallida. The most numerous parasitoid species associated with this community isLeptopilina australis. BecauseL. australis was previously unknown in western Europe, we present the characters to distinguish it form its close relativeL. clavipes. Experiments on host species selection and survival ofL. australis showed that this parasitoid mainly usesD. limbata as host. Olfactometer experiments showed thatL. australis is attracted by the odour of decaying hogweed stalks, especially when these contain larvae ofD. limbata. L. australis is also strongly attracted by the odour of stinkhorns, a habitat in which it has never been found in nature.D. phalerata is the dominant fly species in stinkhorns, and is not a host ofL. australis. We offer a possible functional explanation for this unexpected habitat choice, by showing thatD. transversa andD. kuntzei, both species found to breed in fungi, are also suitable hosts forL. australis. We also discuss habitat choice with regard to a proposed phylogeny of theLeptopilina species in temperate Europe. Finally, we discuss niche overlap ofL. australis with the otherLeptopilina species.


The rate and pattern of fetal hemoglobin decline adjusted to sickle cell status of newborns in Dar es Salaam, Tanzania: A prospective cohort study.
Foetal haemoglobin (%) and foetal cell (%) according to sickle cell status.


Validation of a pediatric single-port laparoscopic surgery simulator.
This study aims to adapt an existing multiport pediatric laparoscopic surgery simulator to be suitable for pediatric single-port laparoscopy and to investigate construct validity for its use as a resource for skills training and assessment. An existing pediatric-sized box trainer was modified to accommodate a commercially available port. A total of 41 participants (18 novices, 16 intermediates and 7 experts) were recruited to complete four curriculum tasks via a single-port access approach. Objective task performance scores were evaluated. Task completion times and performance scores were significantly different between novices and experts for the peg transfer (P = 0.02, P = 0.008 respectively), pattern cut (P < 0.001, P < 0.001 respectively) and ligating loop (P = 0.038, P = 0.035 respectively). There were significant differences in outcomes between novices and intermediates for all tasks, including the intracorporeal suture task (P ≤ 0.001). There were no significant differences in outcomes between intermediates and experts for all tasks. The Pediatric Laparoscopic Surgery (PLS) simulator can be easily adapted for single-port laparoscopic surgery to be construct valid for the peg transfer, ligating loop and pattern cut tasks. There is scope for additional tasks to be developed that focus on the unique technical challenges and skills associated with single-port techniques.


A multi-institutional observational study of testosterone levels after testosterone pellet (Testopel(®)) insertion.
Implantable testosterone pellets were approved by the Food and Drug Administration in 1972 for the treatment of testosterone deficiency syndrome (TDS). Clinical use of this testosterone delivery modality has been limited until its recent reintroduction (Testopel(®) , Slate Pharmaceuticals, Durham, NC, USA). Six academic institutions collaborated and combined their databases to more fully characterize serum testosterone levels after the pellet implantations. To assess the time-dependent serum testosterone levels after subcutaneous testosterone pellets in clinical practice for the treatment of TDS. Data were retrospectively pooled and analyzed from data in six academic institutions. Variables included patient age, total testosterone concentrations before and after implantation, the number of testosterone pellets implanted, and the time from implantation to measurement of serum testosterone concentrations. Three hundred eighty men undergoing 702 insertions were included for analysis using JMP (version 4.0.4; SAS Institute, Cary, NC, USA). Main outcome measures were postimplantation total testosterone levels and investigator-reported adverse events. Testosterone levels as a function of the number of pellets implanted and time from implantation were assessed. Implantation of six to ≥10 testosterone pellets (450 to ≥750 mg) increased total testosterone into the therapeutic range at 1 month postimplantation and sustained therapeutic levels (>300) for 4-6 months. Higher pellet numbers (10-12 pellets) were associated with higher, more consistent, and longer maintenance of testosterone levels within the therapeutic range. Four extrusions and three hematomas were reported early in our experience; other investigator-reported adverse events were generally mild to moderate in nature and transient in duration. No subjects required analgesics. Testosterone pellets (Testopel(®) , Slate Pharmaceuticals) provide sustained levels of testosterone for at least 4 months and up to 6 months in men with TDS. Implantation of ≥8 pellets achieved optimal results with respect to peak mean testosterone level and duration of effect. Testosterone pellets were generally well tolerated.


Selective generation of Kerr combs induced by asymmetrically phase-detuned dual pumping of a fiber ring cavity.
We numerically and experimentally investigate the asymmetrically phase-detuned dual pumping of a passive inhomogeneous fiber ring cavity. This configuration originates from the fine control of frequency mismatch between the frequency spacing of the bichromatic pump and the free spectral range of the cavity. Multicomb states at offset frequencies can be selectively generated by means of the mismatch parameter and the coexistence of Turing and Faraday instabilities.


The calcium-binding protein calretinin-22k is detectable in the serum and specific cells of cancer patients.
Calretinin-22k (CR-22k), an alternatively spliced form of calretinin (CR) belongs to the EF-hand family of calcium-binding proteins and is expressed in several colon adenocarcinoma cell lines (e.g. WiDr, HT-29). Serum samples of cancer patients were screened with a sandwich ELISA technique using the CR-specific antiserum 7696. Highly positive samples were analyzed by Western blots and immunohistochemistry. CR-22k was detected in the serum of several patients and values were as high as 0.19 microgram/ml. Western blot analysis confirmed the identity of the bound protein as CR-22k. The highest concentrations were detected in patients with colon or breast cancer, but also in a patient with ischemic necrosis of the gut. CR immunoreactivity was localized to epithelial cells, nerve fibres, cells of the connective tissue and to mesothelial cells. Our results establish that CR-22k is detectable in the serum of cancer patients under specific pathological conditions.


Recent trends in the incidence, treatment, and prognosis of patients with heart failure and atrial fibrillation (the Worcester Heart Failure Study).
Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases and the co-occurrence of AF and HF has been associated with reduced survival. Data are needed on the potentially changing trends in the characteristics, treatment, and prognosis of patients with acute decompensated HF (ADHF) and AF. The study population consisted of 9,748 patients hospitalized with ADHF at 11 hospitals in the Worcester, Massachusetts, metropolitan area during 4 study years (1995, 2000, 2002, and 2004). Of the 9,748 patients admitted with ADHF, 3,868 (39.7%) had a history of AF and 449 (4.6%) developed new-onset AF during hospitalization. The rates of new-onset AF remained stable (4.9% in 1995; 5.0% in 2004), but the proportion of patients with pre-existing AF (34.5% in 1995; 41.6% in 2004) increased over time. New-onset and pre-existing AF were associated with older age, but pre-existing AF was more closely linked to a greater co-morbid disease burden. The use of HF therapies did not differ greatly by AF status. Despite this, new-onset AF was associated with a longer length of stay (7.5 vs 6.1 days) and greater in-hospital death rates (11.4% vs 6.6%). In contrast, pre-existing AF was associated with lower rates of postdischarge survival compared to patients with no AF (p <0.05 for all). The mortality rates improved significantly over time in patients with AF. In conclusion, AF was common among patients with ADHF, and the proportion of ADHF patients with co-occurring AF increased during the study period. Despite improving trends in survival, patients with ADHF and AF are at increased risk of in-hospital and postdischarge mortality.


Bond selectivity in electron-induced reaction due to directed recoil on an anisotropic substrate.
Bond-selective reaction is central to heterogeneous catalysis. In heterogeneous catalysis, selectivity is found to depend on the chemical nature and morphology of the substrate. Here, however, we show a high degree of bond selectivity dependent only on adsorbate bond alignment. The system studied is the electron-induced reaction of meta-diiodobenzene physisorbed on Cu(110). Of the adsorbate's C-I bonds, C-I aligned 'Along' the copper row dissociates in 99.3% of the cases giving surface reaction, whereas C-I bond aligned 'Across' the rows dissociates in only 0.7% of the cases. A two-electronic-state molecular dynamics model attributes reaction to an initial transition to a repulsive state of an Along C-I, followed by directed recoil of C towards a Cu atom of the same row, forming C-Cu. A similar impulse on an Across C-I gives directed C that, moving across rows, does not encounter a Cu atom and hence exhibits markedly less reaction.


An evidence-based approach to the use of rotational and directional coronary atherectomy in the era of drug-eluting stents: when does it make sense?
Advances in percutaneous interventions have profoundly changed the way we manage patients with coronary and peripheral arterial disease. Though the use of stents, particularly drug-eluting stents, is the preferred method for revascularization because of ease of use and lower restenosis rates, there are many short comings. Ostial and bifurcation lesions as well as heavily calcified and tortuous arteries remain problematic. Mechanical debulking with rotational and direct coronary atherectomy may be beneficial in these situations. In this review, we present the general concepts of mechanical debulking and attempt to summarize the available data on its use in the setting of drug-eluting stents. In addition, we will discuss its special role in the management of peripheral arterial disease.


Leadership skills curriculum development for residents and fellows: A needs-assessment.
Non-technical skills (NTS) curricula have demonstrated success in surgical residencies. The purpose of this study is to examine the need for a structured leadership curriculum at our institution. A needs-assessment survey analyzing the importance of leadership domains, previously validated by Kazley et al. was delivered to 240 general surgery staff. Respondent groups were broken down into: Attendings, Residents, and Multi-Disciplinary. Statistical analyses were conducted using Cronbach's Alpha (α = 0.9259) and Fisher's exact test (pre-set p-value = 0.05). The importance of each competency was compared among groups and importance was defined as >75% important and very important responses. Nineteen of 33 competencies were important for all groups, including 3 with 100% importance: interpersonal communication, team-work, and problem-solving. Several competencies showed statistically significant differences among groups. A diverse range of surgery staff agreed that 19 leadership domains are important to teach residents, with some variance among respondent groups.


Prediction of liver toxicity and mode of action using metabolomics in vitro in HepG2 cells.
Liver toxicity is a leading systemic toxicity of drugs and chemicals demanding more human-relevant, high throughput, cost effective in vitro solutions. In addition to contributing to animal welfare, in vitro techniques facilitate exploring and understanding the molecular mechanisms underlying toxicity. New 'omics technologies can provide comprehensive information on the toxicological mode of action of compounds, as well as quantitative information about the multi-parametric metabolic response of cellular systems in normal and patho-physiological conditions. Here, we combined mass-spectroscopy metabolomics with an in vitro liver toxicity model. Metabolite profiles of HepG2 cells treated with 35 test substances resulted in 1114 cell supernatants and 3556 intracellular samples analyzed by metabolomics. Control samples showed relative standard deviations of about 10-15%, while the technical replicates were at 5-10%. Importantly, this procedure revealed concentration-response effects and patterns of metabolome changes that are consistent for different liver toxicity mechanisms (liver enzyme induction/inhibition, liver toxicity and peroxisome proliferation). Our findings provide evidence that identifying organ toxicity can be achieved in a robust, reliable, human-relevant system, representing a non-animal alternative for systemic toxicology.


Dynamic relaxation in algebraic reconstruction technique (ART) for breast tomosynthesis imaging.
A major challenge in Digital Breast Tomosynthesis (DBT) is handling image noise since the 3D reconstructed images are obtained from low dose projections and limited angular range. The use of the iterative reconstruction algorithm Algebraic Reconstruction Technique (ART) in clinical context depends on two key factors: the number of iterations needed (time consuming) and the image noise after iterations. Both factors depend highly on a relaxation coefficient (λ), which may give rise to slow or noisy reconstructions, when a single λ value is considered for the entire iterative process. The aim of this work is to present a new implementation for the ART that takes into account a dynamic mode to calculate λ in DBT image reconstruction. A set of initial reconstructions of real phantom data was done using constant λ values. The results were used to choose, for each iteration, the suitable λ value, taking into account the image noise level and the convergence speed. A methodology to optimize λ automatically during the image reconstruction was proposed. Results showed we can dynamically choose λ values in such a way that the time needed to reconstruct the images can be significantly reduced (up to 70%) while achieving similar image quality. These results were confirmed with one clinical dataset. With simple methodology we were able to dynamically choose λ in DBT image reconstruction with ART, allowing a shorter image reconstruction time without increasing image noise.


Thyrotropin-induced plasma membrane protein modifications in porcine thyroid cells.
Highly purified plasma membranes were obtained from isolated porcine thyroid cells maintained in conditions of culture in the presence of thyrotropin (stimulated cells) or in their absence (non-stimulated cells). Analyses of both types of membranes by high-resolution sodium dodecylsulfate-polyacrylamide slab gel electrophoresis showed reproducible quantitative differences in protein bands of apparent molecular weight 38,000, 36,000 and inconstantly 96,000. Phosphorylation of membranes by [gamma-32P]ATP was 2-3 times higher in membranes from thyrotropin-stimulated than in membranes from non-stimulated cells. About 20 32P-labeled bands were detected by slab gel electrophoresis in denaturing conditions, among which the catalytic subunit of Na+, K+ ATPase was characterized. In addition, plasma membranes from thyrotropin-stimulated cells contained a firmly bound [14C]glucosamine-containing glycoprotein probably related to an aggregation-promoting factor. 125I-labeled thyroglobulin and components of unknown nature were associated with plasma membranes from thyrotropin-stimulated cells. Whether they participate in the structure and function(s) of the plasma membrane or represent contaminants of the preparation is not clear at the present time.


Increase of MT1-MMP, TIMP-2 and Ki-67 proteins in the odontogenic region of the rat incisor post-shortening procedure.
MT1-MMP and TIMP-2 are well known for their roles in remodelling of extracellular matrix components. However, reports are emerging on the involvement of these molecules in cell kinetics. In the rat incisor tooth, a shortening treatment increases the eruption and cell proliferation rates. However, the role of MT1-MMP and TIMP-2 proteins in these processes is still to be evaluated. Male Wistar rats were divided in two groups. In the normofunctional group (NF) the lower teeth of the rats remained in a normal eruption process. In the hypofunctional group (HP) rats their lower left incisor tooth was shortened every 2 days during 12 days. The eruption rate was estimated during the shortening period and MT1-MMP, TIMP-2 and Ki-67 protein expression from the odontogenic region was measured after the treatment. In HP groups an increase in eruption rate, and in MT1-MMP/TIMP-2 and Ki-67 expression were observed. We conclude that there is a relationship between the increase in eruption rate, and in levels of MT1-MMP, TIMP-2 and Ki-67 in the HP group. This suggests that MT1-MMP and TIMP-2 may have some role in cell proliferation during the eruption of the rat incisor tooth.


The "German connection": a survey of the antecedents and patterns of drug abuse in veterans returning from European service.
Questionnaire responses were obtained from 20 servicemen returning from European duty (Germany) enroute to their homes following discharge for drug dependency. A descriptive analysis is provided in terms of personal background, drug history, and motivating factors for initiation and continuation of drug use in Europe.


Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content.
One of the hallmarks of Alzheimer's disease (AD) is the accumulation of amyloid beta (Aβ) peptides in the brain. The processing of amyloid precursor protein (APP) into Aβ is dependent on the location of APP in the membrane, membrane lipid composition and, possibly, presence of lipid rafts. In this study, we used atomic force microscopy (AFM) to investigate the interaction between transmembrane fragment APP672-726 (corresponding to Aβ1-55) and its amyloidogenic mutant L723P with membranes combining liquid-ordered and liquid-disordered lipid phases. Our results demonstrated that most of the APP672-726 is located either in the liquid-disordered phase or at the boundary between ordered and disordered phases, and hardly ever in rafts. We did not notice any major changes in the domain structure induced by APP672-726. In membranes without cholesterol APP672-726, and especially its amyloidogenic mutant L723P formed annular structures and clusters rising above the membrane. Presence of cholesterol led to the appearance of concave membrane regions up to 2 nm in depth that were deeper for wild type APP672-726. Thus, membrane cholesterol regulates changes in membrane structure and permeability induced by APP that might be connected with further formation of membrane pores.


Bringing Forth Within: Enhabiting at the Intersection Between Enaction and Ecological Psychology.
Baggs and Chemero (2018) propose that certain tensions between enaction and ecological psychology arise due different interpretations about what is meant by the "environment." In the enactive approach the emphasis is on the umwelt, which describes the environment as the "meaningful, lived surroundings of a given individual." The ecological approach, on the other hand, emphasises what they refer to as the habitat "the environment as a set of resources for a typical, or ideal, member of a species." By making this distinction, these authors claim they are able to retain the best of both the ecological and the enactive approaches. Herein I propose an account of the individuation of habits that straddles this distinction, what I call a compatabilist account. This is done in two parts. The first part teases out a host of compatibilities that exist between the enactive account as developed by Di Paolo et al. (2017) and the skilled intentionality framework as developed by Bruineberg and Rietveld (2014) and Rietveld and Kiverstein (2014). In part two these compatibilities are brought together with the that these compatibilities can be brought together with the philosophy of Gilbert Simondon to develop the notion of enhabiting. Enhabiting describes a set of ongoing processes by which an umwelt emerges from and is reproduced within the relationship between an embodied subject and their habitat. Thus, enhabiting points toward a point of intersection between enaction and ecological psychology. To enhabit is bring forth (to enact), within (to inhabit).


Carthami flos extract against carbon tetrachloride-induced liver fibrosis via alleviating angiogenesis in mice.
Angiogenesis is a pathological phenomenon contribute to the development of chronic liver diseases, and anti-angiogenic therapy is an effective strategy to alleviate liver fibrosis. Carthami flos, a medicinal and edible herb, has the effects of improving blood circulation and regulating angiogenesis. However, the anti-angiogenic effect of Carthami flos in liver fibrosis remains unknown. We investigated the protective effect and therapeutic mechanism of Carthami flos extract (CFE) on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. The liver injury and collagen deposition were observed and evaluated by conducting HE, Masson, and Sirius red staining, testing the serum biochemical indexes (ALT, AST, ALP, γ-GT), and measuring the contents of HYP and four indexes of liver fiber (Col-IV, LN, HA, PC-III). Simultaneously, the expressions of α-SMA and Collagen-I were detected to determine the activation of hepatic stellate cells (HSCs). Subsequently, we measured the expressions of angiogenesis-related proteins such as PDGFRB, ERK1/2, p-ERK1/2, MEK, p-MEK, HIF-1α, VEGFA, VEGFR2, AKT and eNOS, and the mRNA levels of PDGFRB and VEGFA. Additionally, immunofluorescence staining and RT-qPCR assays were carried out to ascertain the expressions of continuous endothelial markers CD31, CD34 and vWF, and scanning electron microscope analysis was performed to observe the number of sinusoidal endothelial fenestrations. Herein, we found that CFE could significantly reduce liver injury and collagen deposition, like the same effect of colchicine. CFE significantly alleviated CCl4-induced liver injury and fibrosis, mainly manifested by reducing the levels of ALT, AST, ALP and γ-GT and decreasing the contents of HYP, Col-IV, LN, HA and PC-III. Additionally, CCl4 promoted the activation of HSCs by increasing the expressions of α-SMA and Collagen-I, while CFE could rectify the condition. Moreover, CFE treatment prevented the CCl4-induced the up-regulation of PDGFRB, p-MEK, p-ERK1/2, HIF-1α, VEGFA, VEGFR2, AKT and eNOS, suggesting that CFE might provide the protection against abnormal angiogenesis. In the meantime, the gradual disappearance of sinusoidal capillarization after CFE treatment was supported by the decreased the contents of CD31, CD34 and vWF, as well as the increased number of sinusoidal endothelial fenestrae. In this study, the reduction of collagen deposition, the obstruction of HSCs activation, the inactivation of angiogenic signaling pathways and the weakening of hepatic sinusoidal capillarization jointly confirmed that CFE might be promising to resist angiogenesis in liver fibrosis via the PDGFRB/ERK/HIF-1α and VEGFA/AKT/eNOS signaling pathways. Nevertheless, as a potential therapeutic drug, the deeper mechanism of Carthami flos still needs to be further elucidated.


Onset of oral lichen planus following dental treatments: A nested case-control study.
The exposure to amalgam restorations has been reported to bring about altered immunity followed by inflammation and infection. This study aimed at identifying whether patients who received restorative or endodontic treatments, or tooth extraction, would have altered odds of developing oral lichen planus (OLP). In this population-based nested case-control study, 421 cases of OLP and 1,684 controls were included after propensity score matching. Logistic regression was used to estimate the adjusted odds ratio (aOR) of OLP in individuals who had received amalgam and composite resin restorations, root canal therapy, and tooth extraction over a follow-up duration of five years. There were no significantly different odds of OLP for those who underwent either amalgam (aOR = 0.948, 95% CI = 0.853-1.053, p = 0.3170) or resin restorations (aOR = 1.007, 95% CI = 0.978-1.037, p = 0.6557) in both anterior and posterior teeth in an observational period of five years after restorations. Root canal therapy was associated with significantly lower odds of OLP, with each additional root canal therapy attenuating the risk of OLP at an aOR of 0.771 (95% CI = 0.680-0.874, p = 0.0001) for both anterior (aOR = 0.786, 95% CI = 0.626-0.986, p = 0.0372) and posterior teeth (aOR = 0.762, 95% CI = 0.650-0.893, p = 0.0008). Likewise, each tooth extraction reduced the risk of OLP, with an aOR of 0.846 (95% CI = 0.772-0.927, p = 0.0003), especially for anterior teeth (aOR = 0.733, 95% CI = 0.595-0.904, p = 0.0037). We reported no significant association between dental restorations and consequent OLP, and significantly lower odds of OLP following both root canal therapy and tooth extraction.


Effect of oral doses of zinc oxide on the secretion of pancreatic juice and bile in sheep.
Three sheep were given zinc oxide three times a week for six weeks at a dose rate of 240 mg zinc kg-1. The pancreatic injury resulting from the zinc oxide dosing varied from minor to severe. There was a large reduction in the rate of flow of pancreatic juice and in the concentrations of protein and amylase in the pancreatic juice from the extensively injured pancreas. Before dosing with zinc oxide, the zinc concentration in pancreatic juice was greater than in bile and increased markedly after zinc oxide dosing commenced. After prolonged dosing, zinc concentrations and output in pancreatic juice varied inversely with the degree of pancreatic injury. The bicarbonate concentration in pancreatic juice was unaffected by the zinc treatment but total output was reduced in the most severely affected sheep because flow rate decreased. In this sheep biliary bicarbonate concentration but not total bicarbonate output was increased.


Chlamydia pneumoniae immunoreactivity in coronary artery plaques of patients with acute coronary syndromes and its relation with serology.
An association between Chlamydia pneumoniae (Cpn) infection and coronary artery disease has been reported and examined by different techniques. However, its immunoreactivity in coronary artery plaques of patients with acute coronary syndrome (ACS) and its relation with serology are less well defined. We divided 40 coronary plaque specimens from 40 patients who underwent thrombectomy or directional coronary atherectomy into an ACS group (n = 22) and a non-ACS group (n = 18). Cpn in specimens was detected immunohistochemically and compared quantitatively. Serum immunoglobulin (Ig)A and IgG antibodies to Cpn and high-sensitivity C-reactive protein (hs-CRP) were measured. The relation between serology and immunohistochemical analysis was also investigated. Cpn immunopositive cells per square millimeter (Cpn+ cells/mm2) in the ACS group were significantly more numerous than in the non-ACS group (median 7.44 vs 1.50, P = .0018). Cpn IgA seropositivity rates and titers in the ACS group were significantly higher than those in the non-ACS group (86.3% vs 22.2%, P = .0002; median titer 1.403 vs 0.545, P = .003). There were no differences in IgG antibodies between the 2 groups. The hs-CRP values (in milligrams per liter) in ACS group were significantly higher than in non-ACS group (median 2.8 vs 1.2, P = .0019). Serum IgA titers in patients with at least 5 Cpn+ cells/mm2 in the specimens were significantly higher than in patients with fewer Cpn+ cells (median 1.52 vs 0.86, P = .026). There was no difference in serum hs-CRP values in patients with more Cpn+ cells but a trend to an increase. Immunohistology frequently detected Cpn in coronary plaques; Cpn+ cells were more prevalent in plaques associated with ACS, and Cpn IgA but not IgG titers were increased with ACS and with high densities of Cpn+ cells within plaque.


What Is Needed to Eradicate Lymphatic Filariasis? A Model-Based Assessment on the Impact of Scaling Up Mass Drug Administration Programs.
Lymphatic filariasis (LF) is a neglected tropical disease for which more than a billion people in 73 countries are thought to be at-risk. At a global level, the efforts against LF are designed as an elimination program. However, current efforts appear to aim for elimination in some but not all endemic areas. With the 2020 goal of elimination looming, we set out to develop plausible scale-up scenarios to reach global elimination and eradication. We predict the duration of mass drug administration (MDA) necessary to reach local elimination for a variety of transmission archetypes using an existing model of LF transmission, estimate the number of treatments required for each scenario, and consider implications of rapid scale-up. We have defined four scenarios that differ in their geographic coverage and rate of scale-up. For each scenario, country-specific simulations and calculations were performed that took into account the pre-intervention transmission intensity, the different vector genera, drug regimen, achieved level of population coverage, previous progress toward elimination, and potential programmatic delays due to mapping, operations, and administration. Our results indicate that eliminating LF by 2020 is unlikely. If MDA programs are drastically scaled up and expanded, the final round of MDA for LF eradication could be delivered in 2028 after 4,159 million treatments. However, if the current rate of scale-up is maintained, the final round of MDA to eradicate LF may not occur until 2050. Rapid scale-up of MDA will decrease the amount of time and treatments required to reach LF eradication. It may also propel the program towards success, as the risk of failure is likely to increase with extended program duration.


Evaluating the Implementation of a Medical Student's Handoff Curriculum During the Surgery Clerkship.
Early introduction to essential communication skills is important. We sought to determine if a handoff curriculum (HC) would improve confidence, decrease anxiety, and increase participation in clinical handoffs during the surgical clerkship. A multi-center prospective cohort study was performed at two medical schools. Training in the intervention group (HC) consisted of a didactic lecture, video review, and practice session. Students completed a pre-clerkship knowledge test and confidence/anxiety/handoff experience questionnaire pre- and post-clerkship. There were no significant differences in pre-clerkship handoff experiences between institutions except having previously witnessed a verbal handoff (School A 96.4% versus School B 76.2%, P = 0.01). While there were no significant differences in post-clerkship confidence or anxiety, HC students were significantly more involved with written sign-outs (52.9% versus 18.2%, P = 0.02) and verbal handoffs (29.4% versus 4.6%, P = 0.03). Medical students exposed to handoff training shared similar confidence and anxiety scores compared to those that were not, however, they were more involved in handoff experiences during their surgical clerkship. Early introduction to handoff skills may encourage greater participation during subsequent clinical experiences.


A randomized, double-blinded, placebo-controlled clinical trial of duloxetine hydrochloride enteric-coated tablets in the treatment of refractory chronic cough.
Refractory cough, a chronic cough with an unclear diagnosis or poor treatment response. The symptoms are often stubborn and persistent, causing serious complications and lowering the patient's quality of life. Cough hypersensitivity syndrome (CHS) is proposed as a potential cause, and reducing sensory nerve hyperresponsiveness is suggested as an effective treatment. However, current drugs have low efficacy and benefit rates and numerous side effects. This trail proposes using duloxetine, a selective 5-HT and norepinephrine reuptake inhibitor, as a potential treatment for refractory cough, which has shown promise in treating pain and depression. Duloxetine may inhibit pain conduction and oxidative stress in peripheral nerves by inhibiting the activity of TRPV1 channels, which play an important role in the peripheral afferent pathway of refractory cough. Meanwhile, the antidepressant effects of duloxetine may also play a role in the treatment of refractory cough. This is a single-center, prospective, randomized, double-blind, and controlled trial. A total of 98 individuals will be randomized in a 1:1 ratio to duloxetine group and placebo control group (starting with 20 mg QD, increasing 20 mg daily until 20 mg TID). After a screening period, the second stage runs from baseline to the 42nd (last) day of treatment, with follow-up visits on the 3rd, 7th, 14th, 21st, 28th, 35th, 42nd and 49th days. The main end-stage observation indicators include objective cough frequency, cough visual analog scale (VAS), cough symptom score, Leicester Cough Questionnaire (LCQ), and cough evaluation test (CET); the secondary end-stage observation indicators include capsaicin cough sensitivity, Patient Health Questionnaire-9 (PHQ-9), Major Depression Inventory (MDI), the Generalized Anxiety Disorder-7 scale (GAD-7), Life Events Scale (LES-32), induced sputum supernatant. The safety measures will be AEs/SAEs, vital signs, liver and kidney function, fecal occult blood test. This study is the first randomized, double-blind, and controlled clinical trial investigating the use of duloxetine in the treatment of refractory coughs. The study aims to provide a high-quality basis for evaluating the efficacy and safety of duloxetine for this condition. Our study was registered in the Chinese Clinical Trials Register ( www.chictr.org.cn/ ) (ChiCTR2000037429) in 28/08/2020.


Effects of milk fermented by Lactobacillus helveticus R389 on immune cells associated to mammary glands in normal and a breast cancer model.
Antitumour activity is an effect attributed to probiotics and fermented foods. Here, the immune cells in mammary glands and cytokine concentration in serum were analyzed using mice fed with milk fermented by Lactobacillus helveticus R389 or L89 (proteolytic-deficient variant), injected or not with breast tumour cells. Mice were fed 7 days with fermented milk, injected with breast tumour cells and 4 days post-injection, they received fermented milk. IgA, CD4, CD8, cytokines and Bcl-2 positive cells in mammary glands and cytokine in serum were determined. Mice fed with L. helveticus R389 fermented milk and injected with tumour cells increased IgA and CD4 positive cells in mammary glands (tumour control increased CD8 + cells). Mice from fermented milk control groups (without tumour cell injection) did not show changes in immune cell or cytokine positive cell numbers. IL-10 increases and IL-6 decreases were more pronounced in mice fed with milk fermented by L. helveticus R389 than in the other groups. This study demonstrated the immunoregulatory capacity of milk fermented by L. helveticus R389 on the immune response in mammary glands in presence of a local pathology (breast tumour). Orally administered fermented products could be used to modify the immune cell activation in distant mucosal sites and maintain these cells alert, but local stimulus was necessary to produce the activation of a local immune response in mammary glands, which could modulate the immune-endocrine relationship in these glands.


Ventricular fibrillation.
Ventricular fibrillation is the most common mechanism of sudden unexpected cardiac death in persons with asymptomatic or symptomatic coronary artery disease. The electrophysiologic mechanisms reviewed in this article include: automaticity of pacemaker fibers, transformation of nonpacemaker into pacemaker fibers, "injury" currents and reentry. Some of the conditions facilitating ventricular fibrillation include bradycardia, long QT syndrome, electrocution, electrolyte imbalance, drugs, sympathetic stimulation and myocardial ischemia. Electrophysiologic studies during acute myocardial ischemia suggest that the earliest activity at the onset of arrhythmia may originate at the sites of the surviving Purkinje fibers or at the epicardial rim. Reentrant arrhythmias arising in ischemic myocardium are attributed to nonhomogeneous distribution of local hyperkalemia and acidosis.


Organomagnesium Based Flash Chemistry: Continuous Flow Generation and Utilization of Halomethylmagnesium Intermediates.
The generation of highly unstable chloromethylmagnesium chloride in a continuous flow reactor and its reaction with aldehydes and ketones is reported. With this strategy, chlorohydrins and epoxides were synthesized within a total residence time of only 2.6 s. The outcome of the reaction can be tuned by simply using either a basic or an acidic quench. Very good to excellent isolated yields, up to 97%, have been obtained for most cases (30 examples).


Acceptance and Commitment Therapy and yoga for drug-refractory epilepsy: a randomized controlled trial.
There is a need for controlled outcome studies on behavioral treatment of epilepsy. The purpose of this study was to evaluate Acceptance and Commitment Therapy (ACT) and yoga in the treatment of epilepsy. The design consisted of a randomized controlled trial with repeated measures (N=18). All participants had an EEG-verified epilepsy diagnosis with drug-refractory seizures. Participants were randomized into one of two groups: ACT or yoga. Therapeutic effects were measured using seizure index (frequency x duration) and quality of life (Satisfaction with Life Scale, WHOQOL-BREF). The treatment protocols consisted of 12 hours of professional therapy distributed in two individual sessions, two group sessions during a 5-week period, and booster sessions at 6 and 12 months posttreatment. Seizure index was continuously assessed during the 3-month baseline and 12-month follow-up. Quality of life was measured after treatment and at the 6-month and 1-year follow-ups. The results indicate that both ACT and yoga significantly reduce seizure index and increase quality of life over time. ACT reduced seizure index significantly more as compared with yoga. Participants in both the ACT and yoga groups improved their quality of life significantly as measured by one of two quality-of-life instruments. The ACT group increased their quality of life significantly as compared with the yoga group as measured by the WHOQOL-BREF, and the yoga group increased their quality of life significantly as compared with the ACT group as measured by the SWLS. The results of this study suggest that complementary treatments, such as ACT and yoga, decrease seizure index and increase quality of life.


Regulation of murine sinonasal cilia function by microbial secreted factors.
Chronic rhinosinusitis is a multifactorial disease resulting in impaired mucociliary clearance. Recent literature suggests that different bacterial species are associated with varied disease severity. We examined the immediate effect of microbial secreted factors on sinonasal ciliary function. Murine primary sinonasal cultures were established in an air-liquid interface (ALI). Bacterial supernatants were isolated from H. influenza, S. pneumoniae, S. aureus, and P. aeruginosa cultures, as well as co-cultures of H. influenza/S. pneumoniae and S. aureus/P. aeruginosa. Controlling for pH and osmolarity, supernatants were administered at 50% concentration to the apical surface of the ALI culture. Basal ciliary beat frequency (CBF) was recorded for 20 minutes, at 5-minute intervals. Control groups were treated with culture broth. At minimum, experiments were performed in triplicate. Stimulated CBF was recorded after mechanical stimulation via short bursts of pressurized air (55 mmHg). All supernatants reduced basal CBF. S. pneumoniae and P. aeruginosa caused significant reduction in CBF at all time points, with the largest decrease of -46.3 ± 1.6% (p < 0.001) for S. pneumoniae and -27.1 ± 2.8% (p < 0.001) for P. aeruginosa. S. aureus caused the basal CBF to decline by -33.0 ± 2.8% (p < 0.001) at 5 minutes, which reversed by 20 minutes. Overall, H. influenza yielded the least change in CBF (-20.0 ± 2.8%, p < 0.002). Co-cultures (H. influenza/S. pneumoniae and S. aureus/P. aeruginosa) resulted in delayed CBF reduction compared with monocultures. P. aeruginosa also blunted stimulated CBF (p < 0.02). Results demonstrated acute decreases in murine sinonasal CBF after exposure to bacterial supernatants. Moreover, P. aeruginosa resulted in diminished ciliary stimulation capacity.


Click chemistry-based novel albumin nanoparticles for anticancer treatment via H2O2 generation.
Glucose oxidase (GOD) exerts anticancer effects by producing hydrogen peroxide (H2O2). However, the use of GOD is limited by its short half-life and low stability. Systemic H2O2 production following systemic absorption of GOD can also cause serious toxicity. GOD-conjugated bovine serum albumin nanoparticles (GOD-BSA NPs) may be useful for overcoming these limitations. Here, bioorthogonal copper-free click chemistry was employed to develop GOD-BSA NPs that are non-toxic and biodegradable and can effectively and rapidly conjugate proteins. These NPs retained their activity, unlike conventional albumin NPs. NPs using dibenzyl cyclooctyne (DBCO)-modified albumin, azide-modified albumin, and azide-modified GOD were fabricated in 10 min. After intratumoral administration, GOD-BSA NPs remained in the tumor for a longer period and displayed better anticancer activity than the effects of GOD alone. GOD-BSA NPs were approximately 240 nm in size and inhibited tumor growth to 40 mm3, whereas tumors treated with phosphate-buffered saline or albumin NPs had sizes of 1673 and 1578 mm3, respectively. GOD-BSA NPs prepared using click chemistry may be useful as a drug delivery system for protein enzymes.


Intranuclear localization of histone acetylation in Physarum polycephalum and the structure of functionally active chromatin.
Based on studies of histone acetylation in vivo in Physarum polycephalum, we present the following hypotheses: (1) Transcription-specific histone acetylation on histones H3 and H4 is a localized process at the nuclear matrix; (2) Histone acetylation in the S phase, which is specific for newly synthesized histones, occurs in an intranuclear nonlocalized process. These hypotheses can explain: (1) the histone specificity of histone acetylation that is dependent on the functional state of the chromatin; (2) the apparent absence of turnover of histone acetylation in the bulk of the chromatin despite a definite low level of steady-state acetylation of all four core histones in bulk chromatin; (3) the pattern of butyrate-induced hyperacetylation observed for active and inactive chromatin.


The role of the implant impression in abutment selection: a technical note.
Selecting the abutment at second-stage implant surgery should combine the experience of both the surgeon and the restorative dentist to avoid complications during prosthetic reconstructions. If an inappropriate abutment is selected, the resultant removal of the abutment and replacement of it with a completely different one is both costly and inefficient. The availability of the healing abutment component has eliminated many of these problems. Making an impression at the implant level allows the dentist ample time to study the restorative needs before selecting the final abutment.


Concealed by darkness: Combination of NMR and HRMS reveal the molecular nature of dissolved organic matter in fractured-rock groundwater and connected surface waters.
Detailed molecular composition of solid phase extracted dissolved organic matter (SPEDOM) collected from fractured-rock groundwater was compared to connected surface river water at two different watersheds in the unconfined chalk aquifer of Champagne in France using full scan ultrahigh resolution electrospray and photoionization Fourier transform ion cyclotron mass spectrometry (FT-ICR MS), Orbitrap tandem MS (MS/MS) and 1H magnetic resonance spectroscopy (NMR). 1H NMR spectroscopy indicated that groundwater SPEDOM carried a higher contribution of aliphatic compounds while surface river waters SPEDOM were enriched in carboxyl-rich alicyclic molecules (CRAM), acetate derivatives and oxygenated units. Furthermore, we show here that use of photoionization (APPI(+)) in aquifer studies is key, ionizing about eight times more compounds than ESI in surface river water samples, specifically targeting the dissolved organic nitrogen pool, accounting for more than 50% of the total molecular space, as well as a non-polar, more aromatic fraction; with little overlap with compounds detected by ESI(-) FT-ICR MS. On the other hand, groundwater SPEDOM samples did not show similar selectivity as less molecular diversity was observed in APPI compared to ESI. Mass-difference transformation networks (MDiNs) applied to ESI(-) and APPI(+) FT-ICR MS datasets provided an overview of the biogeochemical relationships within the aquifer, revealing chemical diversity and microbial/abiotic reactions. Finally, the combination of ESI(-) FT-ICR MS and detailed Orbitrap MS/MS analysis revealed a pool of polar, anthropogenic sulfur-containing surfactants in the groundwaters, likely originating from agricultural runoff. Overall, our study shows that in this aquifer, groundwater SPEDOM contains a significantly reduced pool of organic compounds compared to surface river waters, possibly related to a combination of lack of sunlight and adsorption of high O/C formulas to mineral surfaces.


Screening for unhealthy alcohol and other drug use by health educators: do primary care clinicians document screening results?
Health educators are increasingly being used to deliver preventive care including screening and brief intervention (SBI) for unhealthy substance use (SU) (alcohol or drug). There are few data, however, about the "handoff" of information from health educator to primary care clinician (PCC). Among patients identified with unhealthy SU and counseled by health educators, the objective of this study was to examine (1) the proportion of PCC notes with documentation of SBI and (2) the spectrum of SU not documented by PCCs. Before the PCC-patient encounter, health educators screened for SU, assessed severity (Alcohol, Smoking, and Substance Involvement Screening Test), and counseled patients. They also conveyed this information to the PCC before the PCC-patient encounter. Researchers reviewed the electronic medical record for PCC documentation of SBI performed by the health educator and/or the PCC. Among patients with the health educator-identified SU, only 69% (342/495) of PCC notes contained documentation of screening by the health educator and/or the PCC. Documentation was found in all encounters with patients with likely dependent SU, but only 62% and 59% of encounters with patients with risky alcohol and drug use, respectively. Documentation of cocaine or heroin use was higher than that of alcohol or marijuana use but still not universal. Although all SU-identified patients had received a brief intervention (from a health educator and possibly a PCC), only 25% of PCC notes contained documentation of a brief intervention. Among patients screened and counseled by health educators for unhealthy SU, SBI was often not documented by PCCs. These results suggest that strategies are needed to integrate SBI by primary care team members to advance the quality of care for patients with unhealthy SU.


Atomic-level tungsten doping triggered low overpotential for electrocatalytic water splitting.
The design of electrocatalysts with lower overpotential is of great significance for water splitting. Herein, cobalt hydroxide carbonate (CCH) has been used as a model to demonstrate the boost of its oxygen evolution reaction (OER) activity by atomic doping of W6+ (W-CCH). The 5 at % W doping reduced the OER overpotential of CCH by 95.3 mV at 15 mA cm-2, and increased the current density by 2.8 times at 1.65 V. 5%W-PCCH || 5%W-CCH-based electrolyzer only required a potential of 1.65 V to afford 10 mA cm-2 for full water splitting. The W6+ in CCH are active sites for O2- adsorption and induced an incesaed electron density near the Fermi level, which facilitates the charge transfer during electrocatalysis. The W6+ doping has been validated as an efficient booster for transition-metal carbonate hydroxides-based electrocatalysts, which has half or more than half-filled d-bands.


Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase.
The AMP-activated protein kinase (AMPK) is a critical regulator of energy balance at both the cellular and whole-body levels. Two upstream kinases have been reported to activate AMPK in cell-free assays, i.e., the tumor suppressor LKB1 and calmodulin-dependent protein kinase kinase. However, evidence that this is physiologically relevant currently only exists for LKB1. We now report that there is a significant basal activity and phosphorylation of AMPK in LKB1-deficient cells that can be stimulated by Ca2+ ionophores, and studies using the CaMKK inhibitor STO-609 and isoform-specific siRNAs show that CaMKKbeta is required for this effect. CaMKKbeta also activates AMPK much more rapidly than CaMKKalpha in cell-free assays. K(+)-induced depolarization in rat cerebrocortical slices, which increases intracellular Ca2+ without disturbing cellular adenine nucleotide levels, activates AMPK, and this is blocked by STO-609. Our results suggest a potential Ca(2+)-dependent neuroprotective pathway involving phosphorylation and activation of AMPK by CaMKKbeta.