[A study on age-related changes of histological structure and DNA repair capacity in oral mucosa].
To investigate the age-related changes of histological structure and DNA repair capacity (P53 protein expression) in oral mucous membrane and try to explain why the elders are prone to oral squamous cell carcinoma. The routine HE staining and an immunohistochemical technical (SP method) were used respectively to study the changes of histological structure and P53 expression in normal oral mucosa of different age groups. The SP staining results were evaluated by semiquantity method. 1. With aging, a series of histological changes were observed in the oral mucosa; 2. With aging, an elevating tendency of P53 protein level emerged in the oral mucosa (P < 0.05). The sensitivity to carcinogenic agents in elder people may be accentuated by the age-related histological changes and DNA repair capacity changes of the normal oral mucosa.


Circ_0008285 silencing suppresses angiotensin II-induced vascular smooth muscle cell apoptosis in thoracic aortic aneurysm via miR-150-5p/BASP1 axis.
Vascular smooth muscle cells (VSMCs) are the predominant cell type of the aortic middle layer, the abnormal number or function of which has been demonstrated to have a role in thoracic aortic aneurysm (TAA). Here, this study aimed to identify the function of circ_0008285 in VSMC apoptosis. Human VSMCs were treated with angiotensin II (Ang II) for functional experiments. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry were applied for function analysis. The interaction between miR-150-5p and circ_0008285 or brain acid-soluble protein 1 (BASP1) was also evaluated by dual-luciferase reporter assay and RNA immunoprecipitation assay. Exosomes were isolated by the commercial kit. A highly expressed circ_0008285 was observed in the aortic tissues of TAA patients and Ang-II-induced VSMCs. Circ_0008285 deficiency dramatically reversed Ang-II-induced proliferation arrest and apoptosis promotion in VSMCs. Circ_0008285 functionally targeted miR-150-5p. MiR-150-5p inhibition attenuated the inhibitory effects of circ_0008285 silencing on Ang-II-evoked apoptosis in VSMCs. BASP1 was verified to be a target of miR-150-5p, and was proved to attenuate miR-150-5p-triggered apoptosis arrest in Ang-II-stimulated VSMCs. Additionally, extracellular circ_0008285 was packaged into exosomes, which could be transferred into the recipient cells. Circ_0008285 silencing could suppress Ang-II-induced VSMCs apoptosis via miR-150-5p/BASP1 axis, adding further understanding of the pathogenesis of TAA.


Bioinspired Andrias davidianus-Derived wound dressings for localized drug-elution.
Local drug delivery has received increasing attention in recent years. However, the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios, such as in the oral cavity or in wound beds after resection of tumors. In this study, we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias davidianus (SSAD) as a wound dressing for localized drug elution. The hydrogel was loaded with aminoguanidine or doxorubicin, and its controlled drug release and healing-promoting properties were verified in a diabetic rat palatal mucosal defect model and a C57BL/6 mouse melanoma-bearing model, respectively. The results showed that SSAD hydrogels with different pore sizes could release drugs in a controllable manner and accelerate wound healing. Transcriptome analyses of the palatal mucosa suggested that SSAD could significantly upregulate pathways linked to cell adhesion and extracellular matrix deposition and had the ability to recruit keratinocyte stem cells to defect sites. Taken together, these findings indicate that property-controllable SSAD hydrogels could be a promising biofunctional wound dressing for local drug delivery and promotion of wound healing.


The practice and infrastructure of dental public health in the United States.
Dental public health is a unique and challenging American Dental Association-recognized specialty because the patient is the entire community or population, such as a school, neighborhood, city, state, or the nation, with a focus on vulnerable populations. Limited resources are maximized through prevention, policies, programs, and organized community efforts to respond to great unmet needs. Although dental public health professionals are few in number, millions of people every day have better oral health because of these professionals, who work on the local, state, and national level.


Author Correction: A normalized template matching method for improving spike detection in extracellular voltage recordings.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Assessing the potential of bioeconomy in Slovakia based on public perception of renewable materials in contrast to non-renewable materials.
There is a need for societal transformation towards bioeconomy, which promotes the replacement of non-renewable natural resources with renewable ones. Slovakia has considerable potential for bioeconomy development, yet this potential remains untapped. This article evaluates the public perception regarding the individual properties of renewable and non-renewable materials and their relation to the potential for bioeconomy development in Slovakia. It is found that Slovak consumers prefer natural renewable materials, regardless of other influencing factors, and realise the need for transformation towards a more sustainable economy.


POCT PT INR - Is it adequate for patient care? A comparison of the Roche Coaguchek XS vs. Stago Star vs. Siemens BCS in patients routinely seen in an anticoagulation clinic.
In this study we examined the difference in patient INR values as measured by the POCT CoaguChek XS device and central laboratory Stago Evolution and Siemens BCS XP analyzers. This study composed of 100 warfarin therapy patients and 20 coagulation normal subjects, showed that the difference between the POCT and clinical laboratory values increased with increasing INR and was exacerbated by the use of different thromboplastin reagents by the POCT and central lab. The CoaguChek XS and on-site Stago analyzers which used human recombinant (ISI=1.01) and rabbit brain thromboplastin (ISI=1.25), respectively, showed reasonable agreement for INR<3.0 (k=0.62) but significant difference for INR≥3.0 (k=0.10). In contrast, the CoaguChek XS and Siemens BCS XP, which both employed human recombinant thromboplastin (BCS ISI=1.02), showed greater agreement for the complete range INR values (INR<3.0 k=0.84; INR≥3.0 k=0.70). ECAA Poller calibrant data showed the automated instruments were performing as expected, indicating that ISI calibrations were correct but insufficient to standardize the INR values for the different thromboplastin methods across the full range of measured INRs. Central lab verification of POCT INR>5.0 with the Stago Evolution prevented adverse treatment events for the warfarin therapy patients in the six months preceding and following this investigation.


Outcome following lumbar disc surgery: the role of fibrosis.
Failed-back surgery syndrome remains a challenge for spinal surgeons. It can be related to several causes, including poor surgical indication, misdiagnosis, surgical technique failure, spondilodiscitis and fibrosis. Fibrosis has been associated with a poorer outcome in lumbar disc surgery, although its role in the generation of symptoms is not yet clear. In this study, the authors have analyzed any possible correlation between the clinical outcome and the degree of fibrosis. Forty consecutive patients were enrolled in a prospective study. All of them had operations in the lower lumbar disc in a single level for the first time. Three months after the operation they were submitted to clinical outcome evaluations and questionnaires, including Numeric Pain Rating scales (NPR) for lumbar and leg pain, the McGill Pain Questionnaire, The Quebec Back Pain Disability scale (QBPD) and Straight Leg Raising test. These data were correlated with the degree of fibrosis as revealed by Magnetic Resonance Imaging (MRI). After 3 months, the NPR values for lumbar and leg pain ranged from 0 to 8 (mean 2.32 and 1.67 respectively). The values of the post-operative QBPD scale ranged from 1 to 71 (mean 25.9). Every patient showed a varied degree of fibrosis on MRI. However, statistical analysis depicted no significant correlation between fibrosis and a poorer clinical outcome for pain and disability. The authors found no correlation between excessive fibrosis with lumbar and leg pain, disability or straight leg resistance. The role of fibrosis in the generation of symptoms in patients who have had lumbar disc surgery should be reevaluated.


In-hospital delay in the diagnosis of breast cancer.
There is evidence that delay in the diagnosis of breast cancer may prejudice survival. The aim of this study was to determine the incidence, time trends and causes of delay in a dedicated breast clinic. The interval between first breast clinic visit and a definitive diagnosis was recorded in all patients with invasive breast cancer between 1988 and 1997. In all patients with a delay of 3 months or more, the case notes were reviewed for evidence of a triple assessment (clinical examination, imaging and needle biopsy). The principal cause of delay was identified. Of 1004 patients with invasive breast cancer, there was a delay in diagnosis of 3 months or more in 42 patients between 1988 and 1997, an incidence of 4.2 per cent. The median delay was 6 months and the median age at diagnosis was 53 (range 27-89) years. Triple assessment was undertaken in 30 patients; ten did not have a needle biopsy performed and three patients had no mammography. The principal cause of delay was: false-negative or inadequate fine-needle aspiration cytology (FNAC) in 19 patients, failure of follow-up in eight, clinical signs did not impress in five, FNAC not carried out in four, false-negative mammogram in three, failure of needle localization in two and one patient did not accept clinical advice. The annual incidence of delay in diagnosis did not change significantly over the 10-year interval. Triple assessment is not sufficiently sensitive to detect every breast cancer and a small incidence of diagnostic delay is therefore inevitable with current techniques.


Circularly Polarized Organic Ultralong Room-Temperature Phosphorescence with A High Dissymmetry Factor in Chiral Helical Superstructures.
Long-lived room-temperature phosphorescence (RTP) of organic materials holds a significant potential for optical information. Circularly polarized organic ultralong room-temperature phosphorescence (CP-OURTP) with extremely high dissymmetry factor (glum ) values is even highly demanded and considerably challenging. Here, an effective strategy is introduced to realize CP-OURTP with an emission decay time of 735 ms and a glum value up to 1.49, which exceeds two orders of magnitude larger than previous records, through a system composed of RTP polymers and chiral helical superstructures. The system exhibits excellent stability under multiple cycles of photoirradiation and thermal treatment, and is further employed for information encryption based on optical multiplexing. The results are anticipated to lay the foundation for the development of CP-OURTP materials in advanced photonic applications.


Chemical mixtures exposure and children's health.
Studies to examine the health of the children with compromised immune and endocrine systems living in different air polluted regions by oil waste were undertaken. A dose-dependent effects of the anthropogenic pollution on the functional immunocompetent cells activity, mainly T-suppressors was observed as well as stimulation of immunoglobulins synthesis and reduction of phagocytic activity of neutrophils. Disconnection of immunoglobulins synthesis with production of high specifity antibodies, antiviral in particular, was registered. Correlation changes between indices of hormonal activity and humoral specific defence leading to an increase in the role of peripheral hormones with immune inhibitory effect were revealed. The informative value of studied indices as environmental pollution bioindicators was considered. They will stimulate further investigations in biomonitoring and its introduction into practice of ecological expertise of dwelling agglomerations.


Variation in leaf carbon isotope discrimination in Encelia farinosa: implications for growth, competition, and drought survival.
Population-level variation in the leaf carbon isotope discrimination (Δ) values was examined in Encelia farinosa, a common Sonoran Desert shrub. There was approximately a 2‰ range in Δ values among different plants. These differences in Δ values among neighboring plants were maintained through time, both under conditions when neighbors were present and after neighbors had been removed. Individuals with high Δ values were found to have an accelerated growth rate when these plants were released from competition for water. Individuals with low Δ values were better able to persist through long-term drought. These data suggest possible tradeoffs between conditions favoring high- and low-Δ-value plants within a natural population. Given the temporal variability in precipitation between years and spatial variability in microhabitat quality in the Sonoran Desert, variation in Δ values among E. farinosa plants will be maintained within a population.


A new and rapid immunochemiluminometric assay for the measurement of Tamm-Horsfall glycoprotein.
Tamm-Horsfall glycoprotein was purified to apparent homogeneity from human urine by repeated precipitation with 0.58 mol/l NaCl and gel permeation chromatography under dissociating conditions on Bio-Gel A1.5M. The protein was found to consist of a single polypeptide chain of Mr 100,000 under non-reducing conditions and Mr 75,000 under reducing conditions. Antibodies to Tamm-Horsfall glycoprotein were raised in rabbits and subsequently purified by affinity chromatography using the glycoprotein linked to Sepharose 4B. The specificity of these antibodies was confirmed by Western blotting and by indirect immunofluorescence staining of human kidney tissue. The purified antibodies were labelled with 4-(2-succinimidyloxycarbonylethyl)phenyl-10-methyl-9-acridinium carboxylate fluorosulphonate, an acridinium ester, to a specific activity of 6 X 10(5) photon counts/ng of protein, and used to establish a two-site immunochemiluminometric assay for the measurement of Tamm-Horsfall glycoprotein in serum and urine. The bound and the free fractions were separated by a second antibody to Tamm-Horsfall glycoprotein linked to paramagnetic particles. The bound antibodies were quantified by chemiluminescence. The assay had a sensitivity of detection of 2 ng/ml and a working range, as determined by inter-assay precision profiles, of 30-500 ng/ml. The range in serum samples from volunteers with normal renal function (n = 92) was 74-520 ng/ml and the mean 24-h excretion rate in healthy subjects (n = 32) was 70 +/- 26 mg.


[Dengue in Burkina Faso (ex-Upper Volta): seasonal epidemics in the urban area of Ouagadougou].
During the rainy season of 1982 30 patients (29 european and 1 voltaic) presented with an intense dengue-like syndrome in Ouagadougou city. 73.3% of these cases possessed anti-flavivirus fluorescent antibodies while 30%, were positive for specific anti-Dengue IgM antibodies. Vero type E 6 cell cultures were used to isolate six strains of Dengue 2 virus; monoclonal antibodies were used for viral identification. These strains constitute the first isolates of human Dengue virus in Upper Volta. Authors present conditions of virus isolations, describe the observed syndrome and discuss the epidemiological interest of this outbreak.


Melanogenesis inhibitory daphnane diterpenoids from the flower buds of Daphne genkwa.
Two new daphnane-type diterpene esters, daphneresiniferins A (1) and B (2), along with seven known diterpenes, yuanhuacine (3), yuanhuadine (4), yuanhuahine (5), genkwadaphnin (6), genkwanine A (7), genkwanine F (8), and genkwanine H (9), were isolated from the methanol extract of the flower buds of Daphne genkwa. Their structures were elucidated on the basis of spectroscopic methods, especially 2D NMR spectra such as HMQC, HMBC, and NOESY. All the isolates were evaluated for their inhibitory effects of the melanogenesis against α-melanocyte stimulating hormone (α-MSH)-activated B16 melanoma cells.


Osteopathic treatment leads to significantly greater reductions in chronic thoracic pain after CABG surgery: A randomised controlled trial.
There are a number of long-term postoperative complications after coronary artery bypass graft (CABG) surgery. Pulmonary function is decreased by 12% and 30%-50% of the patients have chronic thoracic pain. This randomised controlled trial with two parallel groups aimed to explore the effectiveness of osteopathic treatments (OTs) on these conditions. The standard care (SC) group and the and OT group received a 12-week standard cardiac rehabilitation programme, which was supplemented with four OTs for the OT group only. The outcome assessors were blinded to the patients' allocation. Eighty-two patients with median sternotomy after CABG surgery were randomly allocated in a 1:1 ratio (SC: n = 42, OT: n = 42). Slow vital capacity and pain intensity were measured at baseline and at 12 weeks and 52 weeks after surgery. Pain intensity was significantly lower in the OT group 12 weeks after surgery (3.6-0.80 vs. 2.6 to 1.2, p = 0.030). One year after surgery, there still was a significantly lower pain intensity in the OT group (3.6-0.56, vs. 2.6 to 1.2, p = 0.014). No significant changes between groups were found in pulmonary function. There were no adverse events reported. From this study, it can be concluded that the addition of OT to exercise-based cardiac rehabilitation may lead to significantly greater reductions in thoracic pain after CABG surgery. This study was registered on ClinicalTrials.gov (NCT01714791).


Model evaluation of starch utilization by acclimated biomass with different culture history under pulse and continuous feeding.
The study involved model evaluation of the fate and utilization of starch by microbial culture acclimated to different growth conditions and feeding regimes. For this purpose, parallel sequencing batch reactors were operated with pulse and continuous feeding of soluble starch at sludge ages of 8 and 2 days. High-rate adsorption was identified as the initial process for starch utilization under all operating conditions. Hydrolysis mechanism acted as the rate limiting mechanism for different substrate removal/storage modes sustained under pulse and continuous feeding at different sludge ages. Together with variable growth kinetics, faster growth conditions also triggered high-rate hydrolysis and relatively slower storage kinetics to ensure the level of substrate supply for faster microbial growth. Model evaluation indicated the presence of particulate sugar adsorbed, especially under continuous feeding. It enabled accurate interpretation of observed particulate sugar values and this way, differentiating glycogen from the adsorbed starch remaining on the biomass.


End-point selection to determine the airway-systemic ratio of inhaled corticosteroids in asthma.
The use of adenosine monophosphate challenge and basal cortisol as short-term surrogate end points of airway-systemic effects of inhaled corticosteroids in asthma is not suitable to properly determine the clinically relevant long-term therapeutic index.


The impact of adverse childhood experiences on healthcare utilization in children.
Adverse childhood experiences (ACEs) are related to long-term negative outcomes. The impact of these experiences on healthcare utilization in children has been understudied. To examine the impact of ACEs on children's healthcare utilization, medical diagnoses, and pharmacological treatment. Children aged 6 months to 17 years who were screened for ACEs in the Behavioral Health Department or in primary care locations as part of an initial consultation visit and who had at least one subsequent healthcare visit during the study period were included in the study. Adverse childhood experiences were measured using the ACE screening questionnaire designed by Felitti et al. (1998). Data from the year following administration of the ACE screening tool were retrospectively extracted from the electronic health record. Overall, 1,183 children met study inclusion criteria. Children with any reported ACEs were more likely to no show appointments (1-3 ACEs incidence rate ratio (IRR) [95 % confidence interval (CI)]: 1.40 [1.11-1.77]; 4+ ACEs IRR [95 % CI]: 1.41 [1.08-1.84]) and to use emergency services (1-3 ACEs IRR [95 % CI]: 1.24 [1.00-1.53]; 4+ ACEs: IRR [95 % CI]: 1.42 [1.11-1.81) than children with no ACEs. Those with 4+ ACEs used the telephone nurse advisor less frequently (1-3 ACEs IRR [95 % CI]: 0.67 [0.53-0.84]; 4+ ACEs IRR [95 % CI]: 0.69 [0.53-0.90]). Although ACE scores were associated with healthcare utilization, insurance status was more robustly associated with healthcare utilization than ACE score. Healthcare systems may employ results from this study to adopt trauma-informed care initiatives. Ensuring that all patients have insurance may be a first step toward improving healthcare utilization.


Rapid dehydration of grape berries dampens the post-ripening transcriptomic program and the metabolite profile evolution.
The postharvest dehydration of grape berries allows the concentration of sugars and other solutes and promotes the synthesis of metabolites and aroma compounds unique to high-quality raisin wines such as the passito wines made in Italy. These dynamic changes are dependent on environmental parameters such as temperature and relative humidity, as well as endogenous factors such as berry morphology and genotype, but the contribution of each variable is not well understood. Here, we compared berries subjected to natural or accelerated dehydration, the latter driven by forced air flow. We followed the evolution of transcript and metabolite profiles and found that accelerated dehydration clearly dampened the natural transcriptomic and metabolomic programs of postharvest berries. We found that slow dehydration over a prolonged duration is necessary to induce gene expression and metabolite accumulation associated with the final quality traits of dehydrated berries. The accumulation of key metabolites (particularly stilbenoids) during postharvest dehydration is inhibited by rapid dehydration conditions that shorten the berry life time.


Pain and sleep after open-heart surgery-inhalation peppermint essence: double-blind randomized clinical trial.
The aim of this study was to determine the effect of inhaling peppermint essence on pain relief and sleep quality after open-heart surgery. In a double-blind randomised clinical trial carried out in Iran in 2020, 64 cardiac patients were selected by convenience sampling and randomly allocated to aromatherapy (n=32) and placebo (n=32) groups. The aromatherapy and control groups received inhaled aromatherapy using peppermint essence and distilled water, respectively. Data gathering tools were the Numeric Pain Rating Scale and St Mary's Hospital Sleep Questionnaire. Data were analysed using an independent t-test, χ2 test, Mann-Whitney U test and generalised estimating equation analysis. The mean severity of pain in the aromatherapy and placebo groups was 3.22±0.88 and 4.56±0.90, respectively, which was a statistically significant difference (p=0.0001). The mean sleep scores after the intervention on day 1 were 20.10±4.90 and 25.76±6.36 in the aromatherapy and placebo groups, respectively, and 18.63±5.56 and 22.62±5.69, respectively, on day 2. The difference between the two groups was statistically significantly different after the intervention in terms of sleep quality (p<0.05). Aromatherapy attenuated pain and improved sleep quality after open-heart surgery. Peppermint essence aromatherapy is therefore recommended after surgery.


A simple and efficient method to rescue very virulent infectious bursal disease virus using SPF chickens.
Reverse genetic systems for efficient generation of very virulent infectious bursal disease virus (vvIBDV) are currently limited. In this study, we have developed a simple and efficient way to rescue vvIBDV using SPF chickens. The genome of a vvIBDV strain, HLJ0504, flanked by hammerhead and hepatitis delta ribozyme sequences, was cloned downstream of the cytomegalovirus enhancer and the chicken beta-actin promoter of the vector pCAGGS. After transfection of DF-1 cells, cell suspensions were injected into the bursa organ of three-week-old SPF chickens. Using this system, vvIBDV was recovered at high titers after one passage, and the rescued vvIBDV remained highly lethal to SPF chickens. This simple and efficient method to rescue vvIBDV will be a valuable tool for better understanding the molecular virulence determinants of vvIBDV.


Progesterone for recurrent miscarriage: truth and deceptions.
Recurrent miscarriage is known to affect 0.5-2% of pregnant women, and the standard investigative protocol fails to identify a specific cause in 50% of cases. Progesterone, a key hormone in pregnancy maintenance, has been used to support early pregnancy for decades. A growing body of considerable evidence indicates that in addition to women with luteal phase defects, women with idiopathic recurrent miscarriage may benefit from progestogen treatment, as progesterone has been shown to be an essential immunomodulatory agent in early pregnancy. It plays a critical role in the expression, modulation and inhibition of various growth factors, cytokines, cell adhesion molecules and decidual proteins. Some studies have revealed a remarkable improvement in pregnancy outcome after progestogen supplementation in women suffering from recurrent miscarriage. As most studies on this topic are of unsufficient statistical power, further research on the efficacy of progestogen treatment in affected women is required.


Improved myocardial recovery after cardioplegic arrest with an oxygenated crystalloid solution.
Possible enhancement of myocardial protection by oxygenation of a crystalloid cardioplegic solution was evaluated in a three-part study. In Part I, canine hearts underwent ischemia followed by heterogeneous cardioplegic arrest for 45 to 60 minutes. Oxygenation led to improved recovery in the left anterior descending region (47% versus 86% recovery, p less than 0.05) (15 minutes of ischemia) and in the circumflex region (9.5% versus 52% recovery, p less than 0.05) (30 minutes of ischemia). Part II was a blind prospective randomized study in 12 patients. It examined creatine kinase, myoglobin, and lactate as well as coronary sinus flow, oxygen consumption, and cardiac work 1 hour after aortic cross-clamping during atrial and during ventricular pacing. No significant difference was demonstrable between control and oxygenated solutions. In Part III, 57 coronary bypass patients were protected with a nonoxygenated solution while 94 patients received an identical oxygenated solution. Twelve-hour creatine kinase levels were similar in the nonoxygenated (9.5 +/- 16 IU, +/- standard deviation) and oxygenated (11 +/- 22 IU) groups if the cross-clamp interval was 28 minutes or less. In patients subjected to longer than 28 minutes of arrest, the 12 hour creatine kinase MB levels were more than twice as high in the nonoxygenated group (26.5 +/- 26 IU) compared to the oxygenated group (9.9 +/- 14 IU, p less than 0.05). In this canine model of heterogeneous cardioplegia and in the routine conduct of coronary bypass operations, oxygenated crystalloid cardioplegia is superior to an identical nonoxygenated solution.


Platelet and fibrin deposition on coronary stents in minipigs: effect of hirudin versus heparin.
The present study was designed to test the hypothesis that the direct thrombin hirudin is more efficient than heparin in reducing thrombus formation after coronary stenting. Despite aggressive anticoagulation, subacute thrombosis of coronary stents is a major complication associated with these new devices. In 19 minipigs indium-111-labeled thrombocytes and iodine-125-labeled fibrinogen were injected 14 to 19 h before coronary implantation of tantalum balloon-expandable stents. In group 1 (n = 6, seven stents), a bolus of heparin (100 U/kg body weight) was given before stenting. Group 2 (n = 6, 11 stents) received both dextran (500 ml) and heparin (a 100-U/kg bolus followed by a continuous infusion of 50 U/kg per h). In group 3 (n = 7, 13 stents), hirudin (recombinant desulphatohirudin HV 1 [CGP 39393] [1 mg/kg]) was given before stent implantation, followed by an infusion of 1 mg/kg per h. All animals were pretreated with aspirin (250 mg intravenously). Activated partial thromboplastin time was prolonged to > 1.8 times control values in groups 2 and 3. Histologic examination after perfusion fixation 12 h after stenting showed a variable extent of thrombus on all stents. Medial tear was observed in three stents in group 1, six stents in group 2 and six stents in group 3. The number of platelets on all stents averaged 116.2 (range 22 to 522) x 10(6) in group 1, 64.3 (range 11 to 169) x 10(6) in group 2 and 19.7 (range 9 to 38) x 10(6) in group 3 (p < 0.05 vs. group 1 and vs. group 2). The increase in platelet deposition, associated with medial tear in all groups, was lowest in the hirudin group. Similarly, fibrin deposition was lowest on stents in hirudin-treated animals. Recombinant hirudin significantly reduces platelet and fibrin deposition on coronary stents compared with the reduction achieved with combined heparin, dextran and aspirin.


Sequential C-H Methylation Catalyzed by the B12 -Dependent SAM Enzyme TokK: Comprehensive Theoretical Study of Selectivities.
TokK is a B12 -dependent radical SAM enzyme involved in the biosynthesis of the β-lactam antibiotic asparenomycin A. It can catalyze three methylations on different sp3 -hybridized carbon positions to introduce an isopropyl side chain at the β-lactam ring of pantetheinylated carbapenem. Herein, we report a quantum chemical study of the reaction mechanism of TokK. A stepwise ''push-pull'' radical relay mechanism is proposed for each methylation: a 5'-deoxyadenosine radical first abstracts a hydrogen atom from the substrate in the active site, then methylcobalamin directionally donates a methyl group to the substrate. More importantly, calculations were able to uncover the origin of observed chemoselectivity and stereoselectivity for the first methylation and regioselectivity for the following two methylations. Further detailed distortion/interaction analysis can help to unravel the main factors controlling the selectivities. Our findings of sequential methylations by TokK could have profound implications for studying other B12 -dependent radical SAM enzymes.


NF-κB in acute pancreatitis: Mechanisms and therapeutic potential.
The incidence of acute pancreatitis (AP) is increasing globally and mortality could be high among patients with organ failure and infected necrosis. The predominant factors responsible for the morbidity and mortality of AP are systemic inflammatory response syndrome and multiorgan dysfunction. Even though preclinical studies have shown antisecretory agents (somatostatin), antioxidants (S-adenosyl methionine [SAM], selenium), protease inhibitors, platelet activating factor inhibitor (Lexipafant), and anti-inflammatory immunomodulators (eg. prostaglandin E, indomethacin) to benefit AP in terms of reducing the severity and/or mortality, most of these agents have shown heterogeneous results in clinical studies. Several years of experimental studies have implicated nuclear factor-kappa B (NF-κB) activation as an early and central event in the progression of inflammation in AP. In this manuscript, we review the literature on the role of NF-κB in the pathogenesis of AP, its early intraacinar activation, and how it results in progression of the disease. We also discuss why anti-protease, antisecretory, and anti-inflammatory agents are unlikely to be effective in clinical acute pancreatitis. NF-κB, being a central molecule that links the initial acinar injury to systemic inflammation and perpetuate the inflammation, we propose that more studies be focussed towards targeted inhibition of NF-κB activity. Direct NF-κB inhibition strategies have already been attempted in patients with various cancers. So far, peroxisome proliferator activator receptor gamma (PPAR-γ) ligand, pyrrolidine dithiocarbamate (PDTC), proteasome inhibitor and calpain I inhibitor have been shown to have direct inhibitory effects on NF-κB activation in experimental AP.


Successful catheter ablation of a slow AV-nodal pathway from the left posteroseptal region.
We present the case of a 44 year old woman with recurrent episodes of supraventricular tachycardia due to AV-nodal reentry (AVNRT). She was refractory to conventional medical treatment and referred to our hospital with the view to catheter ablation of the slow AV-nodal pathway. AVNRT of the common type was easily induced performing stimulation from the high right atrium and proximal coronary sinus. Other forms of supraventricular tachycardia were definitely ruled out during further electrophysiologic study. Repetitive RF applications around the right posteroseptal region failed to cure the tachycardia which remained inducible with a typical jump in the AH interval. Extensive RF applications from posteroinferior to the midseptum including the area of the proximal coronary sinus and its os were ineffective as well.AVNRT was transiently but reproducibly eliminated while burns were applied to the high midseptum but AVNRT reoccured within 20 minutes. Finally after retrograde passage of the aortic valve with a 4 mm tip ablation catheter, RF was applied to the left postero to midseptal region. An accelerated junctional rhythm was immediately observed and AVNRT remained non-inducible from that time onwards. It is concluded that an atypical posterior extension of the AV node with predominant leftatrial course might be responsible for this unusual success of slow pathway elimination from left posteroseptal.


Interleukin-6-174-genotype, sepsis and cerebral injury in very low birth weight infants.
We investigated the association between the interleukin 6 (IL-6)-174-genotype and unfavorable outcomes in preterm infants since it has been reported that the IL-6-174GG-genotype is associated with increased susceptibility to sepsis, and the IL-6-174CC-genotype is more common in preterm infants with severe intraventricular hemorrhage (IVH). We studied 1206 preterm infants with a birth weight below 1500 g. In contrast to previously published data, the frequency of IVH grade IV, periventricular leukomalacia, ventricular-peritoneal-shunting or death was not different between infants with different IL-6-genotypes: IL-6-174GG (n = 430) 8%, IL-6-174GC (n = 605) 9% and IL-6-174CC (n = 167) 12% (P = 0.2 for IL-6-174CC vs GG + GC). Furthermore, we were not able to confirm previously reported association between sepsis and the IL-6-174GG-genotype. Blood-culture-proven sepsis occurred in 19% of IL-6-174GG-carriers (n = 157), 26% of IL-6-174GC-carriers (n = 193) and 27% of infants carrying the IL-6-174CC-genotype (n = 67). We were not able to confirm previously reported associations between sepsis, cerebral injury and the IL-6-174-genotype in VLBW-infants.


Esterases of laboratory-reared and field-collected cotton boll weevils, Anthonomus grandis Boh.: polymorphism of adult esterases and formal genetics of esterase II.
The esterases of the cotton boll weevil were separated by polyacrylamide gel electrophoresis into four major regions. These were named Est I-IV in order of migration from anode to origin. Polymorphism was observed in all regions. The Est II region was shown to consist of no more than two bands (fast and slow). The inheritance of the fast and slow bands of Est II was demonstrated to be controlled by codominant autosomal alleles. Analysis of the gene frequency of the Est II region showed that one field population was consistent with the Hardy-Weinberg law (P = 0.995), while a second field population was not at equilibrium (P less than 0.001).


Personality and male-female influences on the EEG alpha rhythm.
The amplitude and frequency of the alpha rhythm was measured in electroencephalic recordings from 45 male and 46 female university students. The mean alpha frequency of the female group was significantly greater than the male group. There was no significant difference in alpha frequency between females in the first half of the menstrual cycle and those in the second half. The relationship between questionnaire measures of psychoticism, extraversion and neuroticism, and the alpha rhythm was investigated using analysis of variance, correlation analysis and factor analysis. Alpha amplitude was significantly greater in extraverted subjects, alpha amplitude and extraversion scores were significantly correlated and both had high loadings on a single factor. No relationship between psychoticism or neuroticism and alpha frequency or amplitude was observed.


A Narrative Review on the Potential Role of Vitamin D3 in the Prevention, Protection, and Disease Mitigation of Acute and Long COVID-19.
The coronavirus disease 2019 (COVID-19) pandemic has challenged global health systems and economies from January 2020. COVID-19 caused by the infectious severe acute respiratory syndrome coronavirus (SARS-CoV-2) has acute respiratory and cardiometabolic symptoms that can be severe and lethal. Long-term physiological and psychological symptoms, known as long COVID-19, persist affecting multiple organ systems. While vaccinations support the fight against SARS-CoV-2, other effective mechanisms of population protection should exist given the presence of yet unvaccinated and at-risk vulnerable groups, global disease comorbidities, and short-lived vaccine responses. The review proposes vitamin D3 as a plausible molecule for prevention, protection, and disease mitigation of acute and long COVID-19. Epidemiological studies have shown that individuals who were deficient in vitamin D3 had worse COVID-19 health outcomes and mortality rates. Higher doses of vitamin D3 supplementation may improve health and survivorship in individuals of various age groups, comorbidities, and severity of disease symptoms. Vitamin D3's biological effects can provide protection and repair in multiple organ systems affected by SARS-CoV-2. Vitamin D3 supplementation can potentially support disease-mitigation in acute and long COVID-19.


Immunity to Ostertagia ostertagi.
Control of ostertagiasis is a major economic problem in the temperate areas of the world. An immunological control scheme for cattle is an important aspect of integrated control and its achievement is dependent on our understanding of how immunity is acquired. Also, host mechanisms regulated by Ostertagia need to be understood in order to address immunological questions. Little is known about acquired immunity to Ostertagia infection in cattle. The degree of immunity is incomplete and its development slow. Evidence is accumulating for impairment of antibody and cellular immune responses by Ostertagia which is responsible for the survival of the parasite in the young host. Other experimental work suggests that local factors, such as eosinophil accumulation, mucosal mast cell kinetics and other cellular and humoral immune responses, may play a role in pathogenesis and immunity. At the present time these areas are also totally unexplored in the study of Ostertagia infection.


Influence of treatment to sacrifice time and the presence of BrdUrd on chemically-induced aberration rates in mouse marrow cells.
4 chemicals, with various modes of clastogenic action were used to evaluate induced chromosomal aberrations in mouse bone marrow at different times after intraperitoneal injection. Aberration frequencies induced by mitomycin C, cyclophosphamide and dimethylbenz[a]anthracene increased with increasing time between treatment and sampling until those time points (approximately 18 h) when significant proportions of second-division metaphases were among the cells being scored; this increase was not obvious following treatment with 4-nitroquinoline 1-oxide. When BrdUrd tablets were implanted prior to treatment and scoring was restricted to first-division metaphases, aberration rates continued to increase for as long as 24 h post-treatment. The presence of BrdUrd did not affect significantly the rate of aberration induction by the chemicals. Our data indicate that the sensitivity of the in vivo mouse marrow assay for clastogenic chemicals can be greatly increased by utilizing BrdUrd to insure the scoring of only first-division metaphases at post-treatment times of approx. 18 h.


Mapping wind erosion hazard with regression-based machine learning algorithms.
Land susceptibility to wind erosion hazard in Isfahan province, Iran, was mapped by testing 16 advanced regression-based machine learning methods: Robust linear regression (RLR), Cforest, Non-convex penalized quantile regression (NCPQR), Neural network with feature extraction (NNFE), Monotone multi-layer perception neural network (MMLPNN), Ridge regression (RR), Boosting generalized linear model (BGLM), Negative binomial generalized linear model (NBGLM), Boosting generalized additive model (BGAM), Spline generalized additive model (SGAM), Spike and slab regression (SSR), Stochastic gradient boosting (SGB), support vector machine (SVM), Relevance vector machine (RVM) and the Cubist and Adaptive network-based fuzzy inference system (ANFIS). Thirteen factors controlling wind erosion were mapped, and multicollinearity among these factors was quantified using the tolerance coefficient (TC) and variance inflation factor (VIF). Model performance was assessed by RMSE, MAE, MBE, and a Taylor diagram using both training and validation datasets. The result showed that five models (MMLPNN, SGAM, Cforest, BGAM and SGB) are capable of delivering a high prediction accuracy for land susceptibility to wind erosion hazard. DEM, precipitation, and vegetation (NDVI) are the most critical factors controlling wind erosion in the study area. Overall, regression-based machine learning models are efficient techniques for mapping land susceptibility to wind erosion hazards.


Influences of protein kinase A and D-cAMP on actin-myosin interaction and energy consumption of cardiac muscles.
To address controversies concerning the effects of beta-adrenergic stimulation on the rate of myocardial cross-bridge cycling, we measured three mechanical variables, isometric tension development, transient tension response to a step stretch in length (< 1% of muscle length), maximum velocity of shortening, and a chemical variable, ATPase activity before and after treatment with the catalytic subunit of protein kinase A (PKA) in demembranated rat right ventricular trabeculae, and also measured three mechanical variables before and after treatment with D-cAMP in intact ryanodine-induced tetanized preparations. PKA treatment (I U/microliter, 40 min) shifted the pCa-tension relation to the right from 5.41 to 5.26 at pCa50 (the [Ca2+] required for half maximal steady tension) without changing the steepness of the pCa-tension relation and the maximum tension. The rate of the transient tension changes was significantly increased after either PKA or D-cAMP treatment (5 mM, 15 min), regardless of the level of isometric tension. Vmax was increased for a given Ca2+ concentration after either the PKA or D-cAMP treatment, despite the reduced level of isometric tension. The PKA treatment also shifted the pCa-ATPase activity to the right slightly from 5.47 to 5.40 at pCa50, but increased the ATPase activity during a given level of steady isometric tension generation, resulting in an increased tension cost (ATPase activity/tension). These results suggest that, in rat right ventricular trabeculae, beta-adrenergic stimulation may increase the rate of cross-bridge cycling by increasing the rate of crossbridge detachment from actin through a PKA-mediated mechanism, although PKA reduces the Ca(2+)-sensitivity of the contractile system.


A needle stick technique for septal myectomy for hypertrophic obstructive cardiomyopathy.
We developed a needle stick technique for treating hypertrophic obstructive cardiomyopathy. Three 21-gauge needles are inserted into the interventricular septum just below the aortic valve annulus beyond the far side of the septal bulge. The right and left needles are both side margins, and the center needle is a guide for the thickness. Each needle plays a role as a mark of resection for the width, length, and thickness. The needles also stabilize the ventricular septum and provide good exposure of the entire septal hypertrophy. This technique is helpful to safely achieve sufficient septal myectomy of a constant thickness.


Comparison of sterilization of reusable endoscopic biopsy forceps by autoclaving and ethylene oxide gas.
Every country has standardized reprocessing guidelines for reducing the risk of microorganism transmission via reusable biopsy forceps. Sterilization is performed either by autoclaving or with the use of ethylene oxide (EO) gas. However, there are no clear standard global recommendations. The aim of this study was to determine whether EO gas or autoclaving is a safer and more effective method for the sterilization of reusable forceps. This was a prospective study conducted at multiple tertiary referral centers. Seventy reusable biopsy forceps that had been reused at least 20 times each were collected from six endoscopy centers. In all, 61 forceps from five centers were sterilized using EO gas, and the nine forceps from the remaining center were placed in an autoclave. We performed real-time polymerase chain reaction (RT-PCR) for Mycobacterium tuberculosis and hepatitis B virus and performed bacterial cultures on the reusable forceps, which were cut into 2- to 3-cm sections. The forceps were also scanned with an electron microscope (EM) to detect surface damage and contamination. Escherichia coli bacteria were cultured from 2 of the 61 (3.3%) reusable biopsy forceps sterilized with EO gas. On EM scanning, abundant debris and tissue materials remained on the cup surfaces of the reused biopsy forceps and on their inner wires. No microorganisms were found on the autoclaved forceps. Sterilization with EO gas may be inadequate because the complicated structure of the forceps may interfere with sterilization. Therefore, for optimum safety, reusable biopsy forceps should be sterilized by autoclaving.


Bacterial translocation induces proinflammatory responses and is associated with early death in experimental severe injury.
An experimental model of severe injury with great lethality was studied to define the impact of bacterial translocation on survival and on inflammatory response. Forty-one rabbits were divided into two groups: A, femur myotomy; and B, myotomy and fracture of the femoral bone. Vital signs and survival were recorded. Serum circulating endotoxins (lipopolysaccharides; LPS) were determined and tissue cultures were performed at necropsy. A subgroup of animals was sacrificed at 48 h post injury; LPS was determined in abdominal aorta and portal vein, apoptosis of spleen cells was assessed by flow cytometry, and ex vivo production of tumor necrosis factor alpha by splenocytes was measured. Tissue bacterial burden was increased in animals that died early (i.e., within 48 h after injury) versus rabbits that died later. Portal vein LPS at 48 h was increased in group B compared with group A, whereas circulating LPS did not differ. No difference in apoptosis of either lymphocytes or macrophages of the spleen was found in group B compared with group A. Following stimulation with LPS or phytohemagglutinin, tumor necrosis factor α production by splenocytes of group B was greater than that of group A. Bacterial translocation primes enhanced proinflammatory responses and it is associated with early death in severe trauma.


Diagnosis and epidemiology of leptospirosis.
Leptospirosis is a zoonosis found worldwide, the main reservoir of which is the rat. Human infection generally results from exposure to contaminated river or lake water or animals. Around 600 cases are diagnosed per year in France. Half of these cases occur in French overseas territories, where the incidence can be more than 100 times higher than in mainland France. Leptospirosis has been under-diagnosed because of non-specific symptoms, inadequate surveillance system, and lack of readily available quick and simple diagnostic tests. Most cases of leptospirosis are currently detected by PCR amplification of bacterial DNA from the blood during the first week after the onset of symptoms, or by detection of antibodies during the second week of the disease. More than 300 serovars have been identified among leptospires, including serovar Icterohaemorrhagiae, the most frequent in human infections. Leptospirosis remains a major public health issue in many developing countries, one century after discovering the causative agent. Leptospirosis is expected to become more important due to a rapid urbanization in developing countries (slums), global warming, and extreme climatic events (floods).


Treatment of t(4;11) acute leukemia with aggressive multiagent chemotherapy. Preliminary results.
Acute leukemia patients with a 4;11 translocation have had a poor prognosis in the past, averaging 9 months survival from diagnosis. Three patients from The Children's Hospital of Denver were reported in 1982--all died. This report describes five additional patients who fared better. Aggressive treatment during induction and maintenance with intensive alternating non-cross-resistant chemotherapeutic agents may have contributed to the improved survival.


Traumatic renal artery dissection.
Hypertension consequent upon traumatic subintimal dissection of the renal artery is described in 2 cases. The pathogenesis and treatment of this uncommon condition are presented.


Management of a giant intracranial aneurysm using surface-heparinized extracorporeal circulation and controlled deep hypothermic low flow perfusion. A case report.
Extracorporeal circulation with controlled hypothermic low flow perfusion was introduced during the surgical treatment of a patient with a giant intracranial aneurysm of the anterior communicating artery. Heparin-coated equipment (Carmeda Bio-Active Surface; CBAS) was utilized, thus reducing the need for systemic heparinization. Direct cannulation of the right atrium and aorta was established through thoracotomy. Blood flow through the circuit was kept at 4.5 l/min during normothermia. Core cooling, in combination with external surface cooling, was performed for 30 min to a temperature of 18 degrees C (nasopharynx). During a period of 25 min, the time for surgical repair of the aneurysm, blood flow was minimized to 0.4 l.min-1, equilibrating central and peripheral blood pressures to approximately 5-10 mmHg (0.65-1.3 kPa). Reperfusion was started immediately after the low flow period concomitantly with rewarming, aiming at a temperature of 36 degrees C following 150 min. The patient could be weaned off the extracorporeal circulation with minimal inotropic support. The postoperative course was uneventful apart from a left-sided hemiparesis, probably due to an infarction in the area of the right pericallosal artery (A2). The patient was weaned off the ventilator after 6 days. He recovered and the hemiparesis regressed slowly.


Bullseye Technique to Optimize S3 Foramen Access: Applying a Trusted Endourology Technique to Pelvic Medicine.
Sacral neuromodulation (SNM) is an advanced therapy that stimulates sacral spinal nerves to modulate bladder or bowel dysfunction and is approved for the treatment of overactive bladder, fecal incontinence, and non-obstructive urinary retention. Prior to implantation, a successful trial period must be performed via percutaneous nerve evaluation (PNE) or a staged trial to assess treatment efficacy. Ideal lead placement in the S3 foramen is imperative to produce an adequate response and successful outcome. Traditional lead placement with fluoroscopic guidance utilizes the anteroposterior (AP) and lateral views. In this abstract we describe an additional modification which may aid lead placement. This video demonstrates the bullseye technique to obtain S3 foramen access for optimal lead placement in SNM. Begin the procedure by placing the patient in the prone position. The medial edges of the S3 foramen are marked bilaterally in the AP view followed by a horizontal marking at the level of S3. The pelvis is imaged with live fluoroscopy starting at 0 degrees and then rotating the C-arm to 30 degrees. This rotation allows the "opening up" of the S3 foramen from an ellipsoid to an oval. The surgeon grasps the needle with a Kelly clamp, placing it at the level of the skin approximately 2 cm cephalad from the horizontal marking. Live fluoroscopy is performed to align the needle with the image intensifier to form the bullseye. Once the correct angle is identified, the needle is advanced. The procedure is repeated on the contralateral foramen. The bullseye technique allows quick and predictable access into S3. It can potentially decrease operating time, minimize needle entries in PNE, and allows the surgeon to access S3 while maintaining proper medial orientation. The bullseye technique can assist surgeons in obtaining optimal access in SNM and can quickly be integrated into current practices.


Increased apoptosis and different regulation of pro-apoptosis protein bax and anti-apoptosis protein bcl-2 in the olfactory bulb of a rat model of depression.
Reduced olfactory bulb (OB) volume and olfactory sensitivity have been observed in depressed patients, the exact mechanisms underlying, however, are still unknown. Our previous study found that decreased neurogenesis and pre-synaptic dysfunction in the OB of a rat model of depression may be responsible for the phenomena. Nevertheless, whether the apoptosis would also play a certain role in this process is not clear. In this study, we investigated the apoptosis in the OB of a chronic unpredictable mild stress (CUMS) rat model of depression using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Simultaneously, the pro-apoptosis protein bax and anti-apoptosis protein bcl-2 were detected by Western blot. The results showed that the number of TUNEL-positive cells increased dramatically in the glomerular layer of the OB of the CUMS rats, accompanied with up-regulated expression of bax protein and down-regulated expression of bcl-2 protein. The findings indicate that increased apoptosis may be attributed to explain at some level for the reduced OB volume and olfactory dysfunction in depressed patients. Moreover, the mitochondria-dependent death pathway might be involved in apoptosis in the OB of the CUMS rats.


Nutrition and Weight Management in the Elderly.
"Aging alters the way the body digests food, absorbs nutrients, and metabolizes energy. Changes in deglutition, digestion, and metabolism in this population are well described and may lead to alterations in oral intake, body composition, and overall health status. Elderly persons are at high risk for developing sarcopenia as well as sarcopenic obesity characterized by accelerated reduction in lean muscle mass and enhancement of body fat. Nutritional screening is important to identify high-risk individuals and facilitate care management planning. The most common assessment tool in elderly patients is the Mini Nutritional Assessment, which analyzes oral intake, health status, and anthropometrics."


"I'll Just Pick It Up…": Women's Acceptability of Self-Sampling Methods for Sexually Transmitted Infection Screening.
Rates of sexually transmitted infection (STI) screening are suboptimal among college women. Self-sampling methods (SSMs) may improve STI screening rates, but critical gaps remain regarding the influential characteristics of SSM to prioritize in intervention development. The purpose of this study was to explore intervention characteristics influencing the decision to adopt SSM among college women. In-depth interviews (n = 24) were conducted with sexually active college women aged 18-24 years to explore preferred intervention characteristics of SSM. Interviews were stratified by screening status (screened or not screened). The instrument was guided by constructs from the Diffusion of Innovation theory and included characteristics of SSM, such as relative advantage, compatibility, complexity, adaptability, and risk and uncertainty. Overall, women felt that the SSM was not complex and that the instructions were straightforward. Participants discussed their strong preference for receiving their results via text or e-mail rather than via telephone. In addition, women described their concerns about mailing their sample and described their concern about potential contamination and tampering. The most salient advantage to use of SSM was avoiding an interaction with a health care provider. This study contributes to an understanding of the salient intervention characteristics influencing the use of SSM for STI screening, which can be leveraged to improve the health of students and improve rates of screening. Findings can be used to inform the development of a future innovative, theory-based intervention that promotes the use of SSM to improve STI screening rates, and ultimately decrease the burden of STI-related disease.


Simple bioseparations using self-cleaving elastin-like polypeptide tags.
We introduce a new method for the purification of recombinant proteins expressed in Escherichia coli using self-cleaving elastin-like polypeptide (ELP) fusion tags without the need for affinity chromatography or proteolytic tag removal. Using this method we obtained high purity, activity and reasonable yields for ten diverse target proteins.


A systematic review and data synthesis of longitudinal changes in white matter integrity after mild traumatic brain injury assessed by diffusion tensor imaging in adults.
This study aimed to review diffusion tensor imaging studies of mild traumatic brain injury (mTBI) in adults with longitudinal acquisition of data and investigate the variability of findings in association with related factors, such as the time post-injury. Eligible studies from PubMed and EMBASE were searched to identify relevant studies for review. Of the 540 studies, 23 observational studies without intervention and with the following characteristics were included: original research in which adults with mTBI were examined, diffusion tensor imaging was acquired at least twice, white matter integrity was investigated by estimating diffusion metrics, and mode of injury was not restricted to sport- or blast-related mTBI. Baseline scans were acquired within 3 weeks post-injury, followed by longitudinal scans within 3 months and at 12 months post-injury. During the acute/subacute period, mixed results (increase, decrease, or no significant change) of fractional anisotropy (FA) were observed compared to those in controls. Some studies reported increased FA during the acute/subacute period compared to controls, followed by normalization of FA. Decreased FA was also reported during the acute/subacute period, which lasted long into the chronic phase. In the acute phase, the mean diffusivity (MD) was greater than that in the controls. Compared to the early phase of injury, MD was reduced in the follow-up phase in most studies in the mTBI group. Insignificant differences in FA and MD have been reported in several studies. Such variability limits the clinical usefulness of diffusion tensor metrics. There was a high variability in reported changes in white matter integrity. Decreased FA not only in acute/subacute but also in long-term period after injury may indicate long-term neurodegenerative processes after mTBI. Nevertheless, longitudinal changes in MD towards normalization suggest possible recovery. Long-term cohort studies with research initiatives should be considered to elucidate brain changes after mTBI.


Insights from nursing for radiologists.
We have observed that former nurses often make very good radiology residents, which leads us to think that nursing offers important lessons to radiology. To be clear, we are not proposing that undergraduate or medical students pursue nursing training so they can enhance their performance in residency - in view of the long course of radiology training, such a suggestion would be highly impractical. But we do believe that aspects of nursing training and practice not typically emphasized in medical education can help radiologists perform better and ultimately promote better patient care.


Roles of renal erythropoietin-producing (REP) cells in the maintenance of systemic oxygen homeostasis.
Erythropoietic induction is critical for enhancing the efficiency of oxygen delivery during the chronic phase of the systemic hypoxia response. The erythroid growth factor erythropoietin (Epo) triggers the erythropoietic induction through the activation of erythroid genes related to cell survival, differentiation, and iron metabolism. Because Epo is produced in renal Epo-producing (REP) cells in a hypoxia-inducible manner, REP cells serve as a control center for the systemic hypoxia response. In fact, the loss of Epo production in REP cells causes chronic severe anemia in genetically modified mice, and REP cell-specific inactivation of PHD2 (prolyl-hydroxylase domain enzyme 2) results in erythrocytosis via overexpression of the Epo gene due to the constitutive activation of HIF2α (hypoxia-inducible transcription factor 2α). REP cells are located in the interstitial spaces between renal tubules and capillaries, where the oxygen supply is low but oxygen consumption is high, for the highly sensitive detection of decreased oxygen supplies to the body. Under disease conditions, REP cells transform to myofibroblasts and lose their Epo-producing ability. Therefore, elucidation of Epo gene regulation and REP cell features directly contributes to understanding the pathology of chronic kidney disease. To further analyze REP cells, we introduce a newly established mouse line in which REP cells are efficiently labeled with fluorescent protein.


Diversity issues in the homecare setting.
As this nation becomes increasingly more culturally diverse and seeks to compete in a global health care market, it is incumbent upon the nursing profession to prepare high-tech homecare nurses who are experts in their ability to make appropriate culturologic assessments of the clients whom they provide care. The culturologically competent high-tech homecare nurse is one who is able to obtain value-free culturologic information and who utilizes that information in the development of culturally sensitive plans of care. This article has provided a framework, with supporting rationale, to assist the high-tech homecare nurse in the gathering of culture-specific data from clients whose care delivery occurs in the richly diverse home setting.


[Chemico-microbiological parameters for diagnosis of periodontal disease].
The authors examined the variations of periodontal markers in relation to severity of periodontal diseases. Furthermore they have considered the changes of bacterial flora in the periodontal disease, before and after removal of subgingival plaque.


A review of genetic counseling for Charcot Marie Tooth disease (CMT).
Charcot Marie Tooth disease (CMT) encompasses the inherited peripheral neuropathies. While four genes have been found to cause over 90 % of genetically identifiable causes of CMT (PMP22, GJB1, MPZ, MFN2), at least 51 genes and loci have been found to cause CMT when mutated, creating difficulties for clinicians to find a genetic subtype for families. Here, the classic features of CMT as well as characteristic features of the most common subtypes of CMT are described, as well as methods for narrowing down the possible subtypes. Psychosocial concerns particular to the CMT population are identified. This is the most inclusive publication for CMT-specific genetic counseling.


A Persistent Hotspot of Schistosoma mansoni Infection in a Five-Year Randomized Trial of Praziquantel Preventative Chemotherapy Strategies.
Persistent hotspots have been described after mass drug administration (MDA) for the control of schistosomiasis, but they have not been studied during the course of a multiyear MDA program. In data from a 5-year study of school-based and village-wide preventive chemotherapy strategies for Schistosoma mansoni, spatial scan statistics were used to find infection hotspots in 3 populations: 5- to 8-year-olds, 9- to 12-year-olds, and adults. Negative binomial regression was used to analyze changes from baseline, and receiver operating characteristic analyses were used to predict which villages would reach prevalence and intensity endpoints. We identified a persistent hotspot, not associated with study arm, where S. mansoni infection prevalence and intensity did not decrease as much as in villages outside the hotspot. Significant differences from baseline were realized after 1 year of MDA: we did not identify factors that moderated this relationship. Villages meeting specified endpoints at year 5 were predicted from prior year data with moderately high sensitivity and specificity. The MDA strategies were less effective at reducing prevalence and intensity in the hotspot compared with other villages. Villages that reached year 5 endpoints could be detected earlier, which may provide the opportunity to amend intervention strategies.


A distinct class of endosome mediates clathrin-independent endocytosis to the Golgi complex.
Mammalian cells endocytose a variety of proteins and lipids without utilising clathrin-coated pits. Detailed molecular mechanisms for clathrin-independent endocytosis are unclear. Several markers for this process, including glycosphingolipid-binding bacterial toxin subunits such as cholera toxin B subunit (CTxB), and glycosyl-phosphatidyl-inositol (GPI)-anchored proteins, are found in detergent-resistant membrane fractions (DRMs), or 'lipid rafts'. The Golgi complex constitutes one principal intracellular destination for these markers. Uptake of both CTxB and GPI-anchored proteins may involve caveolae, small invaginations in the plasma membrane (PM). However, the identity of intermediate organelles involved in PM to Golgi trafficking, as well as the function of caveolins, defining protein components of caveolae, are unclear. This paper shows that molecules which partition into DRMs and are endocytosed in a clathrin-independent fashion, accumulate in a discrete population of endosomes en route to the Golgi complex. These endosomes are devoid of markers for classical early and recycling endosomes, but do contain caveolin-1. Caveolin-1-positive endosomes are sites for the sorting of caveolin-1 away from Golgi-bound cargoes, although caveolin-1 itself is unlikely to have a direct function in PM to Golgi transport.


The pharmacokinetics of methotrexate after intravenous administration of methotrexate-loaded proliposomes to rats.
The pharmacokinetics and tissue distribution of methotrexate (MTX) were investigated after intravenous (i.v.) injection of free MTX (treatment I), MTX-loaded proliposomes (treatment II), and empty proliposomes mixed manually with free MTX (treatment III), 8 mg kg-1, to rats using an HPLC assay. After i.v. infusion in 1 min, the plasma concentration of MTX (Cp), the area under the plasma concentration-time curve (AUC, 639 versus 913 micrograms min mL-1), the terminal half-life (t1/2, 48.8 versus 397 min), the mean residence time (MRT, 8.40 versus 325 min), and the apparent volume of distribution at steady state (Vss, 98.1 versus 2800 mL kg-1) were significantly higher; however, the total body clearance (CL, 12.5 versus 8.76 mL min-1 kg-1), renal clearance (CLR, 4.49 versus 2.78 mL min-1 kg-1), non-renal clearance (CLNR, 7.50 versus 5.99 mL min-1 kg-1), and the amount of MTX excreted in urine (Xu, 808 versus 685 micrograms, p < 0.0948) were significantly lower from treatment II than from treatment I. This could be due to the fact that some of the MTX-loaded liposomes (formed immediately after hydration of MTX-loaded proliposomes) are entrapped in tissues and the rest are present in the plasma (higher MRT and Vss from treatment II), and MTX is slowly released from MTX-loaded liposomes (higher t1/2 from treatment II). In the present HPLC assay, the concentrations of MTX represent the sum of free MTX and MTX loaded in liposomes (higher Cp and AUC, slower CL from treatment II). After i.v. infusion in 1 min, some pharmacokinetic parameters, such as t1/2, MRT, and Vss, were significantly different between treatments I and III; however, the differences seemed to be smaller than those between treatments I and II. After 30 min from i.v. infusion, the tissue to plasma (T/P) ratios of MTX in kidney and stomach from treatment II were significantly lower than those from treatment I. This suggested that the i.v. administration of MTX-loaded proliposomes might have fewer side effects in the organs than that of free MTX. The mean amount of MTX loaded in MTX-loaded proliposomes was 2.54 mg/g proliposomes and the MTX was released slowly from hydrated MTX-loaded proliposomes when incubated with phosphate-buffered saline (PBS), rat plasma, or rat liver homogenate.


Interaction of DnaK with ATP: binding, hydrolysis and Ca+2-stimulated autophosphorylation.
The autophosphorylation of DnaK from Escherichia coli using ATP as phosphate donor is markedly stimulated by Ca+2 and to a lesser degree by Mn+2. Mg+2 and other divalent ions are without effect in this reaction. Lanthanum, an agonist/antagonist of Ca+2, is also effective in stimulating the autophosphorylation. In contrast, Mg+2 but not Ca+2, markedly stimulates the hydrolysis of ATP catalyzed by DnaK. Also at 0 degrees, ATP forms a stable complex with DnaK without hydrolysis that is independent of cations. About 15% of the DnaK in E. coli is associated with membrane vesicles where it also can be phosphorylated in the presence of Ca+2.


Isolation and characterization of proteoglycans synthesized by adult human gingival fibroblasts in vitro.
The proteoglycans synthesized by fibroblasts derived from healthy human gingivae were isolated and characterized. The largest medium proteoglycan was excluded from Sepharose CL-4B but not from Sepharose CL-2B; it was recovered in the most-dense density gradient fraction and identified as a chondroitin sulfate proteoglycan. The medium contained two smaller proteoglycans; one contained predominantly chondroitin sulfate proteoglycan, while the other was comprised predominantly of dermatan sulfate proteoglycan and was quantitatively the major species. The largest proteoglycan in the cell layer fraction, excluded from both Sepharose CL-2B and Sepharose CL-4B, was found in the least-dense density gradient fraction and contained heparan sulfate and chondroitin sulfate proteoglycan. It could be further dissociated by treatment with detergent, suggesting an intimate association with cell membranes. Two other proteoglycan populations of intermediate size were identified in the cell layer extracts which contained variable proportions of heparan sulfate, dermatan sulfate, or chondroitin sulfate proteoglycan. Some small molecular weight material indicative of free glycosaminoglycan chains was also associated with the cell layer fraction. Carbohydrate analysis of the proteoglycans demonstrated the glycosaminoglycan chains to have approximate average molecular weights of 25,000. In addition, N- and O-linked oligosaccharides which were associated with the proteoglycans appeared to be sulfated in varying degrees.


Evaluation of low back muscle surface EMG signals using wavelets.
To compare the ability of observers to correctly detect the reaction time of erector spinae response to unexpected load by inspecting nonprocessed electromyographic signals versus inspection of wavelet transformed electromyographic signals and versus automatic detection on the same wavelet transformed signals. Traditionally, electromyographic signal analysis is performed using Fourier transform based methods. However, muscle response to transients such as unexpected load, have limitations when using these methods of electromyographic processing. A comparison was made of the three methods using the same signals attained during sudden loading of the trunk. 11 chronic low back pain patients and eleven normal subjects were investigated in sudden loading. Surface electromyographic signals were obtained from the erector spine muscle at L3. The ability of observers to detect reaction time of erector spinae muscle responses of nonprocessed electromyographic signals versus inspection of wavelet transformed electromyographic signals versus an automatic peak detection program was determined. The results have shown that the spine muscle reaction time was easier and more accurately determined in the wavelet domain rather than in its original signal representation. Wavelet transform methods improved the analysis of electromyographic signals in the time domain by facilitating the determination of the time of muscle activity. Wavelet transform could be a valuable tool for electromyographic analysis in resolving the psychophysical problem of perception involved in the analysis of nonprocessed signals. In clinical environments, where the speed and the accuracy of the analysis of electromyographic signal is critical, the wavelet based signal processing could be very important.


Zingiberis rhizoma mediated enhancement of the pharmacological effect of aconiti lateralis radix praeparata against acute heart failure and the underlying biological mechanisms.
Aconiti Lateralis Radix Praeparata (Fuzi), a type of Chinese materia medica, has been used to treat acute and chronic heart failure (HF) in traditional Chinese medicine and has been proven in numerous animal studies. It is also well-known that Zingiberis Rhizoma (Ganjiang) is ineffective in the treatment of HF, but it can enhance the anti-HF effect of Fuzi. However, the mechanism underlying this compatibility is still not well investigated. To investigate this mechanism, a model of acute heart failure (AHF) in SD rats induced by propafenone hydrochloride was established in this study. After oral treatments of Ganjiang, Fuzi or a combination of the two drugs in rats with AHF, heart function [e.g., heart rate (HR) and the maximal rising and declining rate of left ventricle pressure (±dp/dtmax)] and serum indicators [e.g., brain natriuretic peptide (BNP), lactate dehydrogenase (LDH) and creatine kinase (CK)] were measured, and histopathological analysis of the heart was also performed. The biological mechanisms were further explored by measuring the protein expression level of the mitochondrial respiration chain complex (MRCC1-4) and the mRNA and protein expression levels of mitochondrial Ca2+ uniporter (MCU) and its upstream proteins, mitochondrial Ca2+ uniporter 1 and mitochondrial Ca2+ uniporter 2 (MICU1-2). The expression levels of key enzymes downstream of the tricarboxylic acid cycle, including pyruvate dehydrogenase (PDH), malate dehydrogenase (MDH) and nicotinamide nucleotide transhydrogenase (NNT), were also measured. As a result, Ganjiang enhanced the therapeutic effect of Fuzi on AHF by raising the HR and ±dp/dtmax; decreasing the serum levels of BNP, LDH and CK; and alleviating histological damage of the myocardial tissue when compared to the treatments of Ganjiang or Fuzi alone. In conclusion, there was an enhancing effect of Ganjiang on the anti-AHF function of Fuzi treatment, and the potential mechanism of this effect may be related to the mitochondrial energy metabolism pathway mediated by MCU.


Trends in length of stay, functional outcomes, and discharge destination stratified by disease type for inpatient rehabilitation in Singapore community hospitals from 1996 to 2005.
To determine the trends in length of stay (LOS), rehabilitation functional outcome, and discharge destination of patients admitted for inpatient rehabilitation from 1996 to 2005 and stratified by disease in Singapore. Retrospective national data were extracted from medical records of community-based inpatient rehabilitation admissions in Singapore from 1996 to 2005. Four community hospitals. There were 12,506 first admissions for rehabilitation; 40.6% were for stroke, 30.4% for fracture, 2.9% for lower limb (LL) joint replacement, 2.3% for LL amputation, 1.9% for cancer, 1.8% for falls, 1.6% for pneumonia, and 18.5% for other illnesses. The overall mean age ± SD was 73.2±11.5 years. Not applicable. LOS, rehabilitation outcomes (rehabilitation effectiveness [R-effectiveness], rehabilitation efficiency [R-efficiency], relative functional efficiency [Relative-FE]), and discharge destination. The overall median LOS for all disease groups decreased by 16.2% (37 to 31d) from 1996 to 2005. The sharpest decline in LOS among the 8 disease groups was observed in the LL amputation group. The overall mean ± SD admission and discharge activities of daily living scores were 45.6±25.7 and 60.3±28.9, respectively; median R-effectiveness was 28.8%, median R-efficiency was 12.9/30d, and median Relative-FE was 27.7%/30d. From 1996 to 2005, mean R-effectiveness increased by 184% (14% to 40%), R-efficiency increased by 104% (9 to 19 units/30d), and Relative-FE increased by 145% (21% to 51%/30d). Among all inpatient admissions, most were discharged home (78.2%), 10.9% were discharged to an acute hospital, and 9.8% were discharged to nursing or sheltered homes, with no significant change during the 10-year period. Rehabilitation outcomes of patients admitted to Singapore's community hospitals have improved between 1996 and 2005 despite a decreasing LOS. Discharge destinations have largely remained unchanged over this period.


Risk of malignant lymphoma following viral hepatitis infection.
We investigated lymphoma risk following hepatitis infection in a case-control study of 274 incident lymphoma cases, defined according to the WHO classification, and 336 population controls in Sardinia, Italy. Part of our study population (198 cases and 219 controls) was included in the EPILYMPH study of Hepatitis C virus (HCV) infection in relation to non-Hodgklin's lymphoma risk. Based on questionnaire information on whether and at what age a diagnosis of hepatitis was posed by a physician, systematic anti-HCV antibodies testing in cases and controls by enzyme-linked immunoassay, and HCV-RNA assessment by PCR analyses in positive samples, we investigated more in detail whether hepatitis non-C is also associated with lymphoma risk, and whether risk varies by clinical form of hepatitis (acute or chronic infection). After adjusting by age, gender, education, and area of birth whether from the study area or elsewhere in Italy, a previous generic diagnosis of hepatitis was associated with a significantly elevated lymphoma risk [odds ratio (OR) = 1.8; 95% CI 1.1, 2.8], which was equally increased for hepatitis B (OR = 1.8; 95% CI 0.9, 3.5), for HCV positive subjects overall (OR = 2.0; 95% CI 0.8, 4.8), and for hepatitis non-B non-C (OR = 1.6; 95% CI 0.7, 3.9). Once concurrent infection from other hepatitis viruses was excluded, acute or chronic hepatitis C was the only one showing a consistent risk increase in all lymphoma subtypes, but follicular lymphoma. Some indications of an excess risk of lymphoma were observed also for acute, but not chronic forms of hepatitis B and hepatitis non-B, non C. Self-limited hepatitis C did not show an association. No significant heterogeneity in the risk of major lymphoma subtype was observed. Our results confirm a role of either acute or chronic active HCV infection in lymphomagenesis. Further studies are warranted to test the hypothesis that acute infection from other hepatitis viruses might also increase lymphoma risk.


Differential effects of caffeine, picrotoxin, and pentylenetetrazol on hippocampal afterdischarge activity and wet dog shakes.
We identified changes in hippocampal afterdischarge activity that follow administration of subcon vulsant doses (one-half the convulsant dose) of analeptic agents with known pharmacological action. Long-Evans rats (N = 104) with chronic bipolar electrodes implanted in the dorsal hippocampus, were injected i.p. with saline, caffeine (75 mg/kg), picrotoxin (2 mg/kg), or pentylenetatrazol (20 mg/kg) in 1 ml/kg volume 15 min before testing. Body temperature was measured at the beginning of the session to determine if significant change was associated with any of the treatments. Beginning at 10 microA, current (2-s train of 50-Hz biphasic pulses) was applied to hippocampal electrodes and intensity was increased in 10-microA steps until the afterdischarge sequence was elicited. Afterdischarge threshold, wet dog shake frequency, and the duration of the primary afterdischarge, the postprimary depression, and the rebound afterdischarge were measured. Caffeine administration produced a dramatic prolongation of the rebound afterdischarge, without affecting the duration of the primary afterdischarge. All other afterdischarge variables were unchanged by the caffeine treatment. Because caffeine blocks adenosine receptors at physiologic concentrations, adenosine action is implicated in the termination of the second, but not the first, spike train. Picrotoxin and pentylenetetrazol had no influence on the EEG, despite evidence of slight (1 degrees C) hypothermia. A decrease in wet dog shake frequency, however, was associated with picrotoxin administration. As picrotoxin and pentylenetetrazol are known gamma-aminobutyric acid (GABA) antagonists, the results suggest that GABA is involved minimally, if at all, in the hippocampal afterdischarge sequence.


Protection of ash (Fraxinus excelsior) trees from ozone injury by ethylenediurea (EDU): roles of biochemical changes and decreased stomatal conductance in enhancement of growth.
Treatments with ethylenediurea (EDU) protect plants from ozone foliar injury, but the processes underlying this protection are poorly understood. Adult ash trees (Fraxinus excelsior), with or without foliar ozone symptoms in previous years, were treated with EDU at 450 ppm by gravitational trunk infusion in May-September 2005 (32.5 ppm h AOT40). At 30-day intervals, shoot growth, gas exchange, chlorophyll a fluorescence, and water potential were determined. In September, several biochemical parameters were measured. The protective influence of EDU was supported by enhancement in the number of leaflets. EDU did not contribute its nitrogen to leaf tissue as a fertiliser, as determined from lack of difference in foliar N between treatments. Both biochemical (increase in ascorbate-peroxidase and ascorbic acid, and decrease in apoplastic hydrogen peroxide) and biophysical (decrease in stomatal conductance) processes regulated EDU action. As total ascorbic acid increased only in the asymptomatic trees, its role in alleviating O(3) effects on leaf growth and visible injury is controversial.


Innate and adaptive immune gene expression in the brain is associated with neuropathological changes after infection with bovine alpha-herpesvirus-5 in mice.
Bovine alpha herpesvirus-5 (BoAHV-5) is related to the development of meningoencephalitis in cattle. Very little is known about the molecular pathways involved in the central nervous system (CNS) damage associated with inflammation during BoHV-5 infection in mice. To better identify the specific immunological pathways triggered by BoAHV-5 infection in mice, we evaluated the mRNA expression of 84 genes involved in innate and adaptive immune responses. We compared gene expression changes in the cerebrum from noninfected and infected mice with BoHV-5 at a 1 × 107 TCID50. Then, we analyzed the association of these genes with neurological signs, neuropathology, and activation of glial cells in response to BoHV-5 infection. Three days after BoAHV-5 infection, increased expression of TNF, IL-2, CXCL10, CXCR3, CCR4, CCL5, IFN-γ, IL-10, IRF7, STAT1, MX1, GATA 3 C3, LIZ2, caspase-1 and IL-1b was found. We also observed the upregulated expression of the CD8a, TBX21 and CD40LG genes and the downregulated expression of the CD4 gene after BoAHV-5 infection. In addition, BoHV-5-infected animals showed higher levels of all the evaluated inflammatory mediators (TNF, IFN-γ and IL-10) on day 3 postinfection. BoAHV-5-infected animals showed neurological changes along with meningoencephalitis, neuropil vacuolation, hemorrhage and reactive gliosis. Astrogliosis and microgliosis, indicated by increased expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), were found throughout the neuropil in infected brains. Moreover, cleaved caspase-3 immunopositive glio-inflammatory cells were visualized around some blood vessels in areas of neuroinflammation in the cerebrum. In agreement on that we found higher cleaved caspase-3 and Iba-1 expression evaluated by western blot analysis in the brains of infected mice compared to control mice. In conclusion, our results revealed.


Double-signal quantification of amoxicillin based on interaction with 4-aminoantipyrine at copper and nitrogen co-doped carbon quantum dots as an artificial nanozyme.
An one-pot hydrothermal method was developed for synthesis of carbon quantum dots co-doped with copper and nitrogen (Cu, N@CQDs). The synthesized Cu, N@CQDs has unique advantages such as high fluorescence quantum yield (39.1%) and high catalytic activity. Oxidative coupling of amoxicillin (AMX) with 4-aminoantipyrine (4-NH2-APE) in the presence of H2O2 as an oxidant to produce pink quinoneimine chromogen was carried out with the aid of Cu, N@CQDs as a peroxidase-like catalyst. This system was used for the colorimetric and fluorometric assays of AMX with reliable results. Colorimetric method is based on the measurement of a pink-colored product at λmax = 505 nm while the fluorometric assay is based on the quenching of the fluorescence emission of Cu, N@CQDs at 440 nm after excitation at 370 nm. For the colorimetric method, the absorption intensity linearly increased over the concentration range 4.3-110.0 µM with LOD (S/N = 3) of 1.3 µM. For the fluorometric method, the emission intensity of Cu, N@CQDs linearly decreased upon addition of AMX in the concentration range 0.2-120.0 µM with a limit of detection (LOD, S/N = 3) of 0.06 µM. The proposed system was applied to the determination of AMX in different real samples such as pharmaceutical capsules, human serum, milk, and conduit water samples with recoveries in the range 95.8-104.1% and relative standard deviation (RSD %) less than 4.1%.


Studies on the frequencies of PGM1, PGM3 and Es-D types from hair roots in Japanese subjects and the determination of these types from old hair roots.
The frequencies in Japanese subjects are reported of hair roots type PGM1, PGM3, and Es-D, and the determination of these types from old hair roots. The gene frequencies were: PGM11, 0.762; PGM21, 0.230; PGM 71, 0.008; PGM13, 0.621; PGM23, 0.379; Es-D1, 0.625; and Es-D2, 0.375. The old hair roots were analysed after storage at 25 degrees C, 4 degrees C and -80 degrees C; the enzyme activities were detected and typed at 25 degrees C within PGM1 10 days, PGM3 4 days, and Es-D 4 days.


Phase IV non-inferiority trials and additional claims of benefit.
Non-inferiority (NI) trials in drug research are used to demonstrate that a new treatment is not less effective than an active comparator. Since phase IV trials typically aim at informing a clinical decision, the value of a phase IV non-inferiority trial hinges also on its clinical relevance. In such trials, clinical relevance would refer to the added benefit claims of a specific drug, apart from efficacy, relative to its comparator drug in the trial. In this study, we reviewed 41 phase IV trials and extracted information on whether the authors mentioned any additional benefit beyond the NI (efficacy) claim of the drug and whether the additional benefit was proven in the trial. We checked whether the additional claim was based on descriptions only or on formal statistical analyses. Our results showed that 22 out of the 41 NI trials mentioned additional benefit of the test drug and most of these claims were related to the safety profile. Of all the post-authorization NI trials that claimed additional benefit, 10 out of 22 NI trials used formal statistical analyses to show additional benefit, and only one included a sample size calculation for the additional benefit prior to the trial. We conclude that there is room for improvement in terms of designing phase IV NI trials with added benefit claims and in proving these additional claims.


[Complex laser therapy of bacterial destruction of the lungs in children].
The complex laser therapy with the use of a helium-neon laser was employed in 115 patients with bacterial destruction of the lungs at the age of from 3 mos to 14 years. The indications for endothoracic, external and intravascular laser therapy and their combination are substantiated. The calculations of the optimal parameters of laser influence, depending on the stage of the disease and optical characteristics of the damaged lung surface, are presented.


High expression of long noncoding RNA LUCAT1 correlates with a poor clinical outcome in solid tumors: A systematic review and meta-analysis.
Extensive studies have been performed to analyze the expression of long non-coding RNA the lung cancer associated transcript 1 (lncRNA LUCAT1) in various cancer types, and the predictive value of high or low lncRNA LUCAT1 level in survival time. We prepared to assess the association between the lncRNA LUCAT1 expression and the prognosis as well as clinical parameters in human cancers. We retrieved completely in some main databases, such as PubMed, Embase, Web of Science, China National Knowledge Internet (CNKI), and Wanfang database. Then we counted the pooled hazard ratio (HR) and odds ratio (OR) with 95 % confidence interval (CI) to investigate the clinical value of lncRNA LUCAT1. We found that overexpression of lncRNA LUCAT1 was highly associated with shorter overall survival (HR = 1.91, 95 % CI: 1.59-2.31, P < 0.00001) through comprehensively analyzing eight of the total eleven eligible papers. Meanwhile, high lncRNA LUCAT1 expression was significantly related to deeper invasion depth (HR = 3.16, 95 % CI: 1.76-5.70, P = 0.0001), larger tumor size (HR = 2.10, 95 % CI: 1.54-2.86, P < 0.00001), advanced clinical stage (HR = 3.52, 95 % CI: 1.98-6.27, P < 0.0001), and more lymph node metastasis (HR = 2.99, 95 % CI: 1.36-6.57, P = 0.006), respectively. Our outcomes suggest that upregulation of lncRNA LUCAT1 in patients with different cancers can predict a shorter survival time and act as an unfavorable prognostic molecular indicator.


Effect of nitric oxide-cyclic GMP-K+ channel pathway blockers, naloxone and metformin, on the antinociception induced by the diuretic pamabrom.
Pamabrom is a diuretic that is effective in treating premenstrual syndrome and primary dysmenorrhea. The aim of this study was to examine the effect of metformin and modulators of the opioid receptor-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-K+ channel pathway on the local antinociception induced by pamabrom. The rat paw 1% formalin test was used to assess the effects. Rats were treated with local administration of pamabrom (200-800 µg/paw) or indomethacin (200-800 µg/paw). The antinociception of pamabrom or indomethacin was evaluated with and without the local pretreatment of the blockers. Local administration of pamabrom and indomethacin produced dose-dependent antinociception during the second phase of the test. Local pretreatment of the paws with naloxone (50 µg/paw), l-nitro-arginine methyl ester (10-100 µg/paw), or 1H-(1,2,4)-oxadiazolo[4,2-a]quinoxalin-1-one (10-100 µg/paw) reverted the antinociception induced by local pamabrom, but not of indomethacin. Similarly, the K+ channel blockers glibenclamide, glipizide, 4-aminopyridine, tetraethylammonium, charybdotoxin, or apamin reverted the pamabrom-induced antinociception, but not of indomethacin. Metformin significantly blocked the antinociception of pamabrom and indomethacin. Our data suggest that pamabrom could activate the opioid receptor-NO-cGMP-K+ channel pathway to produce its peripheral antinociception in the formalin test. Likewise, a biguanide-dependent mechanism could be activated by pamabrom and indomethacin to generate antinociception.


Metabolic Stress in the Transition Period of Dairy Cows: Focusing on the Prepartum Period.
All modern, high-yielding dairy cows experience a certain degree of reduced insulin sensitivity, negative energy balance, and systemic inflammation during the transition period. Maladaptation to these changes may result in excessive fat mobilization, dysregulation of inflammation, immunosuppression, and, ultimately, metabolic or infectious disease in the postpartum period. Up to half of the clinical diseases in the lifespan of high-yielding dairy cows occur within 3 weeks of calving. Thus, the vast majority of prospective studies on transition dairy cows are focused on the postpartum period. However, predisposition to clinical disease and key (patho)physiological events such as a spontaneous reduction in feed intake, insulin resistance, fat mobilization, and systemic inflammation already occur in the prepartum period. This review focuses on metabolic, adaptive events occurring from drying off until calving in high-yielding cows and discusses determinants that may trigger (mal)adaptation to these events in the late prepartum period.


Seven reconstructions of the orbital and periorbital region with a contralateral orbitonasolabial flap.
Blasius designed the first orbitonasolabial flap in 1842, which has since, been reshaped by many other surgeons. Three years ago, we were confronted with a difficult reconstructive case where ipsilateral local flaps were insufficient to cover a huge defect of the periorbital region. We performed 11 cadaver dissections to determine the type of vascularisation of the orbitonasolabial flap and to define its arc of rotation prior to contralateral use. This contralateral orbitonasolabial flap was subsequently applied to seven cases with satisfactory results.


Clinical and epidemiological features discriminating confirmed COVID-19 patients from SARS-CoV-2 negative patients at screening centres in Madagascar.
Early and fast detection of COVID-19 patients help limit the transmission and wide spread of the virus in the community and will have impact on mortality by reducing the incidence of infection among vulnerable people. Therefore, community-based screening is critical. We aimed to identify clinical signs and symptoms and epidemiological features that could help discriminate confirmed cases of COVID-19 from SARS-CoV-2 negative patients. We found that age (aOR:1.02, 95%CI:1.02-1.03, p < 0.001), symptoms onset between 3 and 14 days (aOR:1.35, 95%CI:1.09)1.68, p = 0.006), fever or history of fever (aOR:1.75, 95%CI:1.42-2.14, p < 0.001), cough (aOR:1.68, 95%CI:1.31-2.04), sore throat (aOR:0.65, 95%CI:0.49-0.85, p = 0.002), ageusia (aOR:2.24, 95%CI:1.42-3.54, p = 0.001), anosmia (aOR:6.04, 95%CI:4.19-8.69, p < 0.001), chest pain (aOR:0.63, 95%CI:0.47-0.85, p = 0.003), myalgia and/or arthralgia (aOR:1.64, 95%CI:1.31-2.04, p < 0.001), household cluster (aOR:1.49, 95%CI:1.17-1.91, p = 0.001) and evidence of confirmed cases in the neighbourhood (aOR:1.92, 95%CI:1.56-2.37, p < 0.001) could help discriminate COVID-19 patients from SARS-CoV-2 negative. A screening score derived from multivariate logistic regression was developed to assess the probability of COVID-19 in patients. We suggest that a patient with a score ≥14 should undergo SARS-CoV-2 PCR testing. A patient with a score ≥30 should be considered at high risk of COVID-19 and should undergo testing but also needs prompt isolation and contact tracing.


Severe systemic hypersensitivity reaction to ibuprofen occurring after prolonged therapy.
A 23-year-old woman with systemic lupus erythematosus had a severe hypersensitivity reaction to the drug ibuprofen. The reaction, documented by rechallenge during hospitalization, was characterized by marked hypotension, fever, rigors, conjunctivitis, meningitis, nausea, arthralgias, and leukopenia. In addition to illustrating the potential diagnostic confusion with infection or lupus flare, this case is of interest in that the reaction developed suddenly despite the patient's uneventful use of the drug for over two years. Collected cases are reviewed from the literature, and the common features are summarized.


MINK is a Rap2 effector for phosphorylation of the postsynaptic scaffold protein TANC1.
Rap1 and Rap2 are similar Ras-like G proteins but perform distinct functions. By the affinity chromatography/mass-spectrometry approach and the yeast two-hybrid screening, we identified Misshapen/NIKs-related kinase (MINK) as a novel Rap2-interacting protein that does not interact with Rap1 or Ras. MINK is a member of the STE20 group of mitogen-activated protein kinase kinase kinase kinases. The interaction between MINK and Rap2 was GTP-dependent and required Phe39 within the effector region of Rap2; the corresponding residue in Rap1 and Ras is Ser. MINK was enriched in the brain, and both MINK and its close relative, Traf2- and Nck-interacting kinase (TNIK), interacted with a postsynaptic scaffold protein containing tetratricopeptide repeats, ankyrin repeats and a coiled-coil region (TANC1) and induced its phosphorylation, under control of Rap2 in cultured cells. These are novel actions of MINK and TNIK, and consistent with a role of MINK as a Rap2 effector in the brain.


Potassium peroxymonosulfate (oxone)--an efficient oxidizing agent for phosphothio compounds.
Potassium peroxymonosulfate (oxone) is demonstrated as a versatile chemoselective and stereospecific oxidizing agent for phosphothio compounds. Its application in nucleotide chemistry is presented.