Dependency of branch diameter growth in young Acer trees on light availability and shoot elongation.
Many biomechanical and theoretical studies have been based on the pipe-model theory, according to which a tree is regarded as an assemblage of pipes, each having the same amount of leaf area or leaf mass. However, the physiological mechanisms underlying the theory have not been extensively examined, particularly at the branch level. We analyzed how branches and trunks thickened in nine young Acer mono Maxim. var. marmoratum (Nichols) Hara f. dissectum (Wesmael) Rehder. and A. rufinerve (Siebold & Zucc.) trees. In particular, we examined the roles of light, allocation of photosynthates and shoot heterogeneity. The cross-sectional area (A) of a branch was proportional to cumulative leaf mass or leaf area of the branch, and cumulative cross-sectional area of the daughter branches (SigmaA) above a branching point was equal to the A of the mother branch. These results indicate the validity of the pipe-model theory. However, the theory was invalid for current-year growth of branch cross-sectional area (DeltaA). The DeltaA/SigmaDeltaA for a branching point was greatest (nearly equal to 1) at the crown surface, decreased with crown depth, and tended to increase again at the trunk base, and DeltaA strongly depended on light interception and the yearly increment of leaves on the branch. We examined factors that influenced DeltaA with multiple regression analysis. The ratio of DeltaA of a branch to branch leaf area depended on both relative irradiance and mean current-year shoot length of the branch, suggesting that diameter growth of a branch is determined by the balance between supply of photosynthates, which depends on light interception by the branch, and demand for photosynthates, which is created by the high cambial activity associated with vigorous shoot elongation.


[Herbal medicines--evidence and drug interactions in clinical practice].
We present an evidence-based literature review of five commonly used herbs in Denmark: St John's wort, ginkgo biloba, valerian, garlic, and ginseng. Various drug interactions are associated with the intake of some herbal medicines, and may result in many clinical conditions. We bring this to the attention of clinical practitioners. Attention to clinical practice and recommendations for discontinuation of the five herbs are given before surgery. Physicians should be aware of and report potential drug interactions and adverse effects, so as to throw more light on this subject.


Rejection and regeneration in peripheral nerve homografts in rats after withdrawal of cyclosporin: morphological and immunohistochemical assessment.
Peripheral nerve homografts 35 mm long were inserted in rats to study rejection and regeneration of nerves after suspension of an immunosuppressant (cyclosporin), and the correlation between the Schwann cells of the host and the donor during the course of regeneration. Sciatic nerve homografts from 36 ACI-RT1a rats were transplanted into Lewis-RT1(1) rats. Isografts were taken from 24 Lewis rats. Cyclosporin 5 mg/kg/day was given subcutaneously for 12 weeks. In the homograft group the myelinated axons that regenerated while the immunosuppressant was being given were covered mainly with Schwann cells from the donor, and after the immunosuppressant was withdrawn both Schwann cells of the donor and axons were rejected. However, while the cyclosporin was being given the Schwann cells of the host migrated into the nerve graft together with a few myelinated axons that escaped rejection, and unmyelinated axons that regenerated after rejection were myelinated by the Schwann cells of host.


Anterior chest wall inflammation by whole-body magnetic resonance imaging in patients with spondyloarthritis: lack of association between clinical and imaging findings in a cross-sectional study.
Inflammatory involvement of the anterior chest wall (ACW) affects the quality of life of patients with spondyloarthritis (SpA), although involvement of the ACW is often neglected on clinical and imaging evaluation. Whole-body (WB) MRI is an imaging method used to assess the ACW in addition to the sacroiliac joints and spine without inconvenience for patients. Our goals in this study were to describe the distribution of ACW inflammation by WB MRI in both early and established SpA and associations between clinical and imaging findings indicative of inflammation. The ACWs of 122 consecutive SpA patients (95 with ankylosing spondylitis (AS) and 27 with nonradiographic SpA (nrSpA)) and 75 healthy controls were scanned by sagittal and coronal WB MRI. The MRI scans were scored independently in random order by seven readers blinded to patient identifiers. Active and structural inflammatory lesions of the ACW were recorded on a web-based data entry form. ACW pain by patient self-report, ACW tenderness on physical examination according to the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and lesions detected by MRI were analyzed descriptively. κ statistics served to assess the agreement between clinical and imaging findings. ACW pain or tenderness was present in 26% of patients, with little difference between AS and nrSpA patients. Bone marrow edema (BME), erosion and fat infiltration were recorded in 44.3%, 34.4% and 27.0% of SpA patients and in 9.3%, 12.0% and 5.3% of controls, respectively. Lesions found by MRI occurred more frequently in AS patients (BME, erosion and fat infiltration in 49.5%, 36.8% and 33.7%, respectively) than in nrSpA patients (25.9%, 25.9% and 3.7%, respectively). The joint most frequently affected by lesions found on MRI scans was the manubriosternal joint. The κ values between clinical assessments and MRI inflammation ranged from -0.10 to only 0.33 for both AS and nrSpA patients. Among SpA patients, 26% had clinical involvement of the ACW. WB MRI signs of ACW inflammation were found in a substantial proportion of patients with AS (49.5%) and nrSpA (25.9%). There was no association between clinical assessments of ACW, including the MASES, and MRI features.


Method of continuous variations: applications of job plots to the study of molecular associations in organometallic chemistry.
Applications of the method of continuous variations (MCV or the Method of Job) to problems of interest to organometallic chemists are described. MCV provides qualitative and quantitative insights into the stoichiometries underlying association of m molecules of A and n molecules of B to form A(m)B(n) . Applications to complex ensembles probe associations that form metal clusters and aggregates. Job plots in which reaction rates are monitored provide relative stoichiometries in rate-limiting transition structures. In a specialized variant, ligand- or solvent-dependent reaction rates are dissected into contributions in both the ground states and transition states, which affords insights into the full reaction coordinate from a single Job plot. Gaps in the literature are identified and critiqued.


Polyamine-assisted rapid and clean cleavage of oligonucleotides from cis-diol bearing universal support.
Polyamine-assisted deprotection conditions have been developed for the rapid and clean cleavage of oligonucleotide chains from a cis-diol group bearing universal polymer support, making it compatible with modern oligonucleotide synthesis via all types of phosphoramidite synthons, including base labile protecting group bearing synthons as well. The synthesized oligonucleotides were found to be comparable with the corresponding standard oligomers with respect to their retention time on HPLC, mass on MALDI-TOF and biological activity in PCR amplification.


The Efficacy of Conbercept in Polypoidal Choroidal Vasculopathy: A Systematic Review.
Thirty studies with 1308 eyes were identified and included in this study. The primary outcome measures were best-corrected visual acuity (BCVA), and secondary outcomes were optical coherence tomography characteristics and polyp regression rates. The pooled results were calculated by the random-effect or fixed-effect model according to the heterogeneity of the data. Despite a large standard deviation in means (SMD) improvement for BCVA and central retinal thickness (CRT) in the conbercept group, there was no statistically significant difference in the other outcomes compared to ranibizumab and aflibercept. However, there was a greater polyp regression rate in the conbercept group at 12 months. This systematic review indicates that conbercept may achieve similar BCVA and CRT improvements as ranibizumab and aflibercept, with a superior rate of polyp regression at 12 months.


Asymptomatic norovirus infection in Mexican children.
Sixty-three children in periurban Mexico City were examined for the occurrence of asymptomatic norovirus (NoV) infection from June to August 1998. NoV was detected in 48 of 161 stool specimens (29.8%), with 31 children (49.2%) having at least one positive stool. Asymptomatic NoV infection occurred commonly during summertime in a Mexican pediatric population.


Proportional assist ventilation, a new approach to ventilatory support. Theory.
The relation between inspiratory effort and ventilatory return (flow and volume) is usually abnormal in patients who require ventilatory support because of respiratory distress. Although all available support methods provide the patient with greater ventilation than would obtain with the same effort while unsupported, the relation between instantaneous effort and ventilatory consequences is not normalized. We describe an approach with which the ventilator simply amplifies patient instantaneous effort throughout inspiration while leaving the patient with complete control over all aspects of breathing pattern (tidal volume, inspiratory and expiratory durations, and flow patterns). This approach is implemented by monitoring the instantaneous rate (V) and volume (V) of gas flow from ventilator to patient and causing applied pressure (P) to change according to the equation of motion [P = f1(V) + f2(V)], where f1 and f2 are appropriately selected functions for the relation between pressure and volume (elastic assist) and pressure and flow (resistive assist). There are several potential advantages to this approach: (1) greater comfort; (2) reduction of peak airway pressure required to sustain ventilation and, hence, the potential for avoiding intubation; (3) less likelihood of overventilation; (4) preservation and enhancement of patient's own reflex, behavioral, and homeostatic control mechanisms since the ventilator essentially becomes an extension of the patient's own muscles; and (5) improved efficiency of negative pressure ventilation.


Inhibition of beta 2glycoprotein I binding to anionic phospholipids: a strategy for the development of antiphospholipid syndrome-specific drugs.
The binding of beta 2glycoprotein I (beta 2GPI) to anionic phospholipids (PL) leads to the presentation of one or more epitopes recognized by autoantibodies from patients with antiphospholipid syndrome (APS). The inhibition of beta 2GPI binding to PL mixtures coated on polystyrene microtiter wells (MTW) and to large, multilamellar PL vesicles (LMV) was examined. Inhibitors included phosphorylated monosaccharide metabolites, myo-inositol monophosphate (IMP), hexaphosphate (IHP) and hexasulfate (IHS), pyrophosphate (PPi), methyl bisphosphonate (MBP) and phenyl phosphonate, and a series of carboxylic and aromatic sulfonic acids. Inhibitors were incubated with beta 2GPI at 37 degrees C for 2 hr either with dimyristoylphosphatidic acid, 80%/dimyristoylphosphatidyl choline, 20% (DMPA/DMPC) coated on MTW or in a suspension of LMV. Phospholipid-bound beta 2GPI to PA/PC on MTW was detected using an immunoassay based on rabbit anti-beta 2GPI; free beta 2GPI (not bound to LMV) was detected by fluorescence spectroscopy. Inhibition was studied over the range 0.01-9.0 mumoles/10(-4)L (0.1-90 mM). Inhibition at maximum concentration in the MTW system ranged from 0.1% (for ADP) to > 94% (for IHP). IHP also provided the greatest inhibition in the LMV system (76%) and was also effective in displacing beta 2GPI already bound to PL surfaces (approximately 50% displaced at 0.25 mM). These data suggest that a strategy for development of therapeutic agents for APS may be based on the use of small cyclic, organic oligoanions such as inositol derivatives to act as ligands for lysine residues at the PL binding site of beta 2GPI.


Management of diabetic foot ulcers and the challenging points: An endocrine view.
Diabetic foot ulcers (DFU) are one of the most challenging complications of diabetes. Up to one-third of patients with diabetes mellitus (DM) may suffer from DFUs during their life. DFU is one of the leading causes of morbidity in patients with DM. The treatment period is challenging, and the recurrence rate of DFUs is high. Hence, establishing prevention strategies is the most important point to be emphasized. A multidisciplinary approach is necessary in the prevention and treatment of DFUs. Patients at risk should be identified, and prevention measures should be taken based on the risk category. Once a DFU is formed, the appropriate classification and evidence-based treatment interventions should be executed. Glycemic control, diagnosis and treatment of vascular disease, local wound care, diagnosis, and treatment of infection should be addressed along with the proper evaluation and management of general health status.


Mitoxantrone and cisplatin in recurrent and/or metastatic salivary gland malignancies.
A phase II study was performed to assess the safety and efficacy of mitoxantrone and cisplatin in locally recurrent and/or metastatic carcinomas of the salivary glands. Between May 1997 and March 2001, a total of 14 patients were entered on this trial. All of them had previously undergone radical resection and 10 were subsequently treated with adjuvant radiation therapy with (n=3) or without (n=7) concomitant chemotherapy. Therapy according to the study protocol consisted of mitoxantrone given as i.v. bolus on day 1 at a dose of 12 mg/m2 and cisplatin given as 90-min infusion at a dose of 30 mg/m2 on days 1-3. We observed two partial responses (14.3%) and stabilization of disease in nine patients (64.3%); progression during therapy was noted in only three cases (21.4%). The median time to progression was 15 months (range 2-36) and the median survival time was 27 months (range 4-54). Myelosuppression was commonly observed. Leukocytopenia occurred in all patients, and was grade 3 or 4 in three (21%) and four (29%) patients. WHO grade 3 thrombocytopenia and anemia was seen in three (21%) and four (29%) patients, respectively. Non-hematologic toxicity was in general mild to moderate except for two cases (14%) of grade 3 nausea and vomiting; overall incidence rates were nausea and vomiting (n=14), stomatitis (n=6), diarrhea (n=3), alopecia (n=11), infection (n=7), increase of serum creatinine (n=3), and peripheral neuropathy (n=3). The combination of mitoxantrone and cisplatin seems to be an active and fairly well-tolerated regimen for the treatment of advanced salivary gland cancers. According to the observed high rate of abrogating progressive disease for a long duration, and the resulting promising progression-free and overall survival time, further investigation seems warranted.


Nodulation and nitrogen fixation in Medicago truncatula strongly alters the abundance of its root microbiota and subtly affects its structure.
The plant common symbiosis signalling (SYM) pathway has shared function between interactions with rhizobia and arbuscular mycorrhizal fungi, the two most important symbiotic interactions between plants and microorganisms that are crucial in plant and agricultural yields. Here, we determine the role of the plant SYM pathway in the structure and abundance of the microbiota in the model legume Medicago truncatula and whether this is controlled by the nitrogen or phosphorus status of the plant. We show that SYM mutants (dmi3) differ substantially from the wild type (WT) in the absolute abundance of the root microbiota, especially under nitrogen limitation. Changes in the structure of the microbiota were less pronounced and depended on both plant genotype and nutrient status. Thus, the SYM pathway has a major impact on microbial abundance in M. truncatula and also subtly alters the composition of the microbiota.


Sleep apnea following percutaneous cervical cordotomy.
Sleep apnea (Ondine's Curse) is an uncommon but potentially fatal complication of percutaneous cervical cordotomy. The authors have had the opportunity to review the case histories of 6 patients who have died of sleep apnea following this procedure. In a series of 112 patients, 144 cervical percutaneous cordotomies were performed from 1977 to 1985--80 unilateral cordotomies and 32 staged bilateral cordotomies. Six (5%) patients died as the result of sleep apnea. Five patients (16%) died following bilateral cordotomy and one (1%) patient with pulmonary disease died following unilateral cordotomy. The clinical data of these 6 patients are presented and unique spinal cord pathology is described in this report. The pathophysiology of the sleep apnea syndrome is also discussed.


Mesoporous carbon stabilized MgO nanoparticles synthesized by pyrolysis of MgCl2 preloaded waste biomass for highly efficient CO2 capture.
Anthropogenic CO2 emission makes significant contribution to global climate change and CO2 capture and storage is a currently a preferred technology to change the trajectory toward irreversible global warming. In this work, we reported a new strategy that the inexhaustible MgCl2 in seawater and the abundantly available biomass waste can be utilized to prepare mesoporous carbon stabilized MgO nanoparticles (mPC-MgO) for CO2 capture. The mPC-MgO showed excellent performance in the CO2 capture process with the maximum capacity of 5.45 mol kg(-1), much higher than many other MgO based CO2 trappers. The CO2 capture capacity of the mPC-MgO material kept almost unchanged in 19-run cyclic reuse, and can be regenerated at low temperature. The mechanism for the CO2 capture by the mPC-MgO was investigated by FTIR and XPS, and the results indicated that the high CO2 capture capacity and the favorable selectivity of the as-prepared materials were mainly attributed to their special structure (i.e., surface area, functional groups, and the MgO NPs). This work would open up a new pathway to slow down global warming as well as resolve the pollution of waste biomass.


Using variability to regulate long term biological rhythms.
We present a model for the generation of precise, long term rhythms from a collection of imprecise, short term oscillators. The model uses variability between oscillators in conjunction with simple coupling rules to produce long term rhythms that are independent of rate equations (e.g. Arrhenius). The rhythms generated by the model are controlled by only two independent parameters and exhibit several physiologically interesting properties, including ready entrainment to external signals and splitting in response to strong constant signals. The model provides several predictions that can be tested in future experiments.


Otx genes and the genetic control of brain morphogenesis.
Understanding the genetic mechanisms that control brain patterning in vertebrates represents a major challenge for developmental neurobiology. The cloning of genes likely to be involved in the organization of the brain and an analysis of their roles have revealed insights into the molecular pathways leading to neural induction, tissue specification, and regionalization of the brain. Among these genes, both Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, contribute to several steps in brain morphogenesis. Recent findings have demonstrated that Otx2 plays a major role in gastrulation and in the early specification of the anterior neural plate while Otx1 is mainly involved in corticogenesis, and Otx1 and Otx2 genes cooperate in such a way that a minimal level of OTX proteins are required for proper regionalization and subsequent patterning of the developing brain. Finally, experiments have shown functional equivalence between Drosophila otd and vertebrate Otx genes, suggesting a surprising conservation of function required in brain development throughout evolution.


Refined mapping and YAC contig construction of the X-linked cleft palate and ankyloglossia locus (CPX) including the proximal X-Y homology breakpoint within Xq21.3.
The gene for X-linked cleft palate (CPX) has previously been mapped in an Icelandic kindred between the unordered proximal markers DXS1002/DXS349/DXS95 and the distal marker DXYS1X, which maps to the proximal end of the X-Y homology region in Xq21.3. Using six sequence-tagged sites (STSs) within the region, a total of 91 yeast artificial chromosome (YAC) clones were isolated and overlapped in a single contig that spans approximately 3.1 Mb between DXS1002 and DXYS1X. The order of microsatellite and STS markers in this was established as DXS1002-DXS1168-DSX349-DXS95-DXS364-DXS 1196-DXS262-DXS110-DXS1066-(DXS1169, DXS1222)-DXS472-DXS1217-DXYS1X. A long-range restriction map of this region was created using eight nonchimeric, overlapping YAC clones. Analysis of newly positioned polymorphic markers in recombinant individuals from the Icelandic family has enabled us to identify DXS1196 and DXS1217 as the flanking markers for CPX. The maximum physical distance containing the CPX gene has been estimated to be 2.0 Mb, which is spanned by a minimum set of five nonchimeric YAC clones. In addition, YAC end clone and STS analyses have pinpointed the location of the proximal boundary of the X-Y homology region within the map.


Pax5 and CD3 immunophenotyping of lymphoma in 2 central bearded dragons.
Two central bearded dragons (Pogona vitticeps), a 3-y-old male and a 5-y-old female, were diagnosed with different manifestations of lymphoma at the Kansas State Veterinary Diagnostic Laboratory between 2019 and 2020. The 3-y-old male was presented for postmortem evaluation and was in poor body condition. Microscopically, nearly all examined organs contained variable numbers of neoplastic round cells. Neoplastic cells in the stomach and liver had moderate immunoreactivity to CD3 consistent with multicentric T-cell lymphoma, and non-neoplastic lymphocytes infiltrating the stomach mass had strong immunoreactivity to Pax5. The 5-y-old female had an ulcerated oral mass located in the right lingual gingiva submitted as an excisional biopsy. Microscopically, the mass was composed of large numbers of neoplastic round cells in the epithelium and connective tissue that were strongly and diffusely positive for CD3 and frequently positive for Pax5, consistent with a dual-positive, localized, epitheliotropic T-cell lymphoma. Neoplastic and non-neoplastic lymphocytes did not stain with CD20 or CD79a. Neoplasms are increasingly reported as a cause of morbidity and mortality in reptiles. Our 2 cases illustrate various presentations of T-cell lymphoma and the effectiveness of CD3 and Pax5 immunohistochemistry in bearded dragons.


American nursing students experience shock during a short-term international program.
When individuals plan to travel internationally, they frequently assume that they will have an enjoyable and memorable experience. But for some, the effects of culture shock may negatively impact their travels and memories. The purpose of this study was to describe culture shock as reported by student nurses who took part in an international short-term program. A phenomenological approach was utilized to elicit the essence of meaning attached to the experience. Eight student nurses in an upper Midwestern university, participated in this international experience. It was concluded that all of the student nurses experienced culture shock to a varying degree and they had varying perceptions of their experiences.


A priori-defined diet quality indexes and risk of type 2 diabetes: the Multiethnic Cohort.
Dietary patterns have been associated with the incidence of type 2 diabetes, but little is known about the impact of ethnicity on this relationship. This study evaluated the association between four a priori dietary quality indexes and risk of type 2 diabetes among white individuals, Japanese-Americans and Native Hawaiians in the Hawaii component of the Multiethnic Cohort. After excluding participants with prevalent diabetes and missing values, the analysis included 89,185 participants (11,217 cases of type 2 diabetes). Dietary intake was assessed at baseline with a quantitative food frequency questionnaire designed for use in the relevant ethnic populations. Sex- and ethnicity-specific HRs were calculated for the Healthy Eating Index-2010 (HEI-2010), the Alternative HEI-2010 (AHEI-2010), the Alternate Mediterranean Diet Score (aMED) and the Dietary Approaches to Stop Hypertension (DASH). We observed significant inverse associations between higher DASH index scores and risk of type 2 diabetes in white men and women, as well as in Japanese-American women and Native Hawaiian men, with respective risk reductions of 37%, 31%, 19% and 21% (in the highest compared with the lowest index category). A higher adherence to the AHEI-2010 and aMED diet was related to a 13-28% lower risk of type 2 diabetes in white participants but not in other ethnic groups. No significant associations with risk of type 2 diabetes were observed for the HEI-2010 index. The small ethnic differences in risk of type 2 diabetes associated with scores of a priori-defined dietary patterns may be due to a different consumption pattern of food components and the fact that the original indexes were not based on diets typical for Asians and Pacific Islanders.


[Chemistry and pharmacology of pyran derivatives. 16. Derivatives of 2-(dialkylamino)-7-methoxychromone with antiallergic activity].
Since 2-(diethylamino)-7-methoxychromone (III a) showed remarkable activity in the rat PCA test, some modifications to its structure were made. For instance new substituents such as chlorine or nitro group were introduced into the molecule and the diethylamino group modified. Thus, 2-(ethylamino)-7-methoxychromone (IX) was prepared by treating 3-methoxyphenol with N-ethylethoxycarbonylacetamide in the presence of phosphorus oxychloride. In this case a small amount of 4-chloro-7-methoxycoumarin was also isolated from the reaction mixture. Moreover compounds (XIV), (XV), (XVII) structurally related to sodium cromoglycate were prepared. The pharmacological screening of some compounds showed a useful antiallergic activity.


Alleviation of cyclic heat stress in broilers by dietary supplementation of mannan-oligosaccharide and Lactobacillus-based probiotic: dynamics of cortisol, thyroid hormones, cholesterol, C-reactive protein, and humoral immunity.
Heat stress (HS), one of the major problems of tropical and subtropical countries, adversely affects the production performance of poultry. Keeping this in view, the present study was designed to investigate some of the biological markers of HS in broilers as modulated by dietary supplementation of mannan-oligosaccharide (MOS) and a Lactobacillus-based probiotic (LBP), either alone or in combination. Two hundred fifty 1-d-old-chicks were randomly divided into 5 groups. From d 22, the birds were either kept at the thermoneutral zone (TN) or exposed to HS to the conclusion of study, d 42. Birds were fed either a corn-based basal diet (TN and HS groups) or the same diet supplemented with 0.5% MOS (HS-MOS group), 0.1% LBP (HS-LBP group), or their combination. Birds were immunized against Newcastle disease virus on d 4 (intraocular; live attenuated) and d 20 (drinking water; live attenuated) and infectious bursal disease virus on d 8 (intraocular; live intermediate strain) and d 24 (drinking water; live attenuated). Birds were killed on d 42 to collect serum for determination of cortisol, thyroid hormones, cholesterol, C-reactive protein, and postvaccinal antibody titers. Results revealed that dietary supplementations decreased (P < 0.05) the serum cortisol and cholesterol concentrations and increased (P < 0.05) thyroxine concentration compared with the HS group without affecting triiodothyronine concentration. The percentage of the C-reactive protein-positive birds was higher (P < 0.05) in the HS group compared with the TN group. Dietary supplementations improved humoral immunity against Newcastle disease virus and infectious bursal disease virus during HS. In conclusion, dietary supplementation of either MOS or LBP alone or in combination can reduce some of the detrimental effects of HS in broilers.


Pregnancy lactogens in the rat conceptus and fetus: circulating levels, distribution of binding, and expression of receptor messenger ribonucleic acid.
To clarify the roles of the rat placental lactogens in embryogenesis and fetal development, we measured the concentrations of rat placental lactogen-II (rPL-II) in fetal rat serum and examined the distribution and expression of rPL-I- and rPL-II-binding sites in rat uteroplacental and fetal tissues. The concentration of rPL-II in fetal rat serum on day 20 of gestation was 28.3 +/- 0.8 ng/ml (mean +/- SEM; n = 6), approximately 1/14th its concentration in maternal serum (398.3 +/- 45.3 ng/ml; n = 6). In the midgestational uterus and placenta, rat PL-I bound specifically to mesometrial decidua and to a capsular layer of stroma overlying the antimesometrial decidua. The binding of radiolabeled rPL-I to these tissues was inhibited by unlabeled rat PRL and human (h) GH, but not by rat GH, suggesting that the rPL-I-binding sites are lactogenic in nature. In the late gestational fetus, rat PL-II bound specifically to fetal adrenal, kidney, small intestine, liver, and pancreas; its binding, like that of rPL-I, was inhibited by rPRL, but not by rGH. rPL-II-binding sites in fetal adrenal were detected as early as day 16, whereas rPL-II-binding sites in fetal kidney and small intestine were not demonstrable until day 18. Lactogenic binding sites in fetal liver and pancreas did not appear until days 19-20. The relative amounts of specific binding of rPL-II to fetal tissues correlated positively with tissue levels of expression of the 4.2- and 1.8-kilobase PRL receptor mRNA transcripts. Radiolabeled hGH, which interacts with somatogenic receptors as well as lactogenic receptors, bound specifically to mesometrial decidua, fetal adrenal, kidney, small intestine, liver, and pancreas. In addition, radiolabeled hGH bound specifically, but with low intensity, to fetal brain. In mesometrial decidua and fetal adrenal, kidney, and small intestine, the binding of hGH was blocked by rPL-II and rPRL, but not by rGH or ovine GH, suggesting the predominance of lactogenic receptors. In contrast, in fetal brain, the binding of hGH was inhibited by rGH, but not by rPL-II, suggesting that the fetal brain contains somatogenic receptors. The presence of rPL-I-binding sites in maternal decidua suggests a paracrine role for the hormone in decidual function at midgestation. The presence of rPL-II in fetal serum and the widespread distribution of rPL-II-binding sites in fetal tissues indicate a role for rPL-II in fetal development.


The implementation of minimally-invasive esophagectomy does not impact short-term outcome in a high-volume center.
Esophagectomy represents the gold standard in the treatment of resectable esophageal cancer. Despite significant improvements in perioperative care, postoperative morbidity and mortality rates remain high. Minimally-invasive surgical techniques introduced to the surgical treatment of esophageal malignancies have been shown to successfully diminish surgical trauma and postoperative morbidity. In the present report we present the stepwise implementation of minimally-invasive techniques in the treatment of esophageal cancer at a high-volume center and its influence on overall patient outcome. A total of 165 consecutive patients with esophagectomy, in two 4-year periods, namely that before (period A) and that after (period B) the implementation of minimally-invasive esophagectomy (MIE) for cancer, were compared. Patients' characteristics, and perioperative, surgical, oncological and survival outcomes were compared. In time period A, 73 patients were treated with open esophagectomy (OE), whereas in time period B 37 patients (40.2%) underwent an OE and 55 (59.8%) a minimally-invasive esophagectomy. Surgical and non-surgical complications did not differ significantly between groups (B: 44.6% vs. A: 54.8%; B: 38% vs. A: 35.6%; p>0.05). Duration of ventilation (B: 1.8 days vs. A: 6.7 days), ICU (B: 5.7 days vs. A: 12.2 days) and hospital stay (B: 20.5 days vs. A: 28.4 days) were significantly reduced in patients of time period B. The number of lymph nodes removed and complete resection rates were comparable (mean=18.1 ± 10.1 lymph nodes; B: 87% R0 vs. A: 93.2% R0). No significant differences between the groups were detectable regarding short-term disease-free or overall survival. The implementation of minimally-invasive esophagectomy is feasible, safe and has the potential to reduce perioperative morbidity without compromising oncological outcome.


The Graz implant supported pendulum, a technical note.
A new, immediately loadable palatal implant with rotational stability and an implant-supported pendulum for patients with dental class II dysgnathia and dental crowding is presented. In seven cases, the treatment goal of distalization of all upper molars without extraction of a single tooth was achieved within 8 months.


Influence of key residues on the reaction mechanism of the cAMP-dependent protein kinase.
The reaction mechanism of the catalytic phosphoryl transfer of cAMP-dependent protein kinase (cAPK) was investigated by semi-empirical AM1 molecular orbital computations of an active site model system derived from the crystal structure of the catalytic subunit of the enzyme. The activation barrier is calculated as 20.7 kcal mol(-1) and the reaction itself to be exothermic by 12.2 kcal mol(-1). The active site residue Asp166, which was often proposed to act as a catalytic base, does not accept a proton in any of the reaction steps. Instead, the hydroxyl hydrogen of serine is shifted to the simultaneously transferred phosphate group of ATP. Although the calculated transition state geometry indicates an associative phosphoryl transfer, no concentration of negative charge is found. To study the influence of protein mutations on the reaction mechanism, we compared two-dimensional energy hypersurfaces of the protein kinase wild-type model and a corresponding mutant in which Asp166 was replaced by alanine. Surprisingly, they show similar energy profiles despite the experimentally known decrease of catalytic activity for corresponding mutants. Furthermore, a model structure was examined, where the charged NH3 group of Lys168 was replaced by a neutral methyl group. The energetic hypersurface of this hypothetical mutant shows two possible pathways for phosphoryl transfer, which both require significantly higher activation energies than the other systems investigated, while the energetic stabilization of the reaction product is similar in all systems. As the position of the amino acid side chains and the substrate peptide is virtually unchanged in all model systems, our results suggest that the exchange of Asp166 by other amino acid is less important to the phosphoryl transfer itself, but crucial to maintain the configuration of the active site in vivo. The positively charged side chain of Lys168, however, is necessary to stabilize the intermediate reaction states, particularly the side chain of the substrate peptide.


Inflated Ovary May Increase the Dispersal Ability of Three Species in the Cold Deserts of Central Asia.
Among the diaspores of angiosperms an inflated ovary (IO) is a novel morphological trait, but no studies have evaluated its effects on dispersal. The primary aim of this study was to determine the effect of the IO on diaspore dispersal in three cold desert species (Carex physodes, Calligonum junceum, and Sphaerophysa salsula). Various morphological features and the mass of fruits and seeds of each species were measured. The role of an IO in diaspore dispersal by wind and water was determined by comparing responses of intact (inflated) IOs and flattened fruits and seeds. Mature diaspores of three species were dispersed by wind, and the IO significantly increased dispersal distance in the field and at different wind speeds in the laboratory. The floating time on water was greater for inflated fruits than flattened fruits and seeds. Since the seed remains inside the IO until after dispersal is completed, the IO of the three species enhances diaspore dispersal. This is the first detailed study on how an IO increases diaspore/seed dispersal. Furthermore, after primary dispersal by wind, secondary dispersal can occur via wind or surface runoff of water, and each method is enhanced by the presence of an IO.


DNA damage and repair in human lymphocytes and gastric mucosa cells exposed to chromium and curcumin.
Human population can be considered as a subject of combined exposure to chemicals. Hexavalent chromium is a well-known mutagen and carcinogen. Curcumin, a popular spice and pigment, is reported to have antineoplastic properties. The single cell gel electrophoresis (Comet assay) is a sensitive technique that allows detecting double- and single-strand DNA breaks caused by a broad spectrum of mutagens. In the present work the ability of curcumin to reduce DNA damage induced by chromium in human lymphocytes and gastric mucosa (GM) cells was investigated by using the comet assay. Chromium at 500 microM evoked DNA damage measured as significant (P < 0.001), about a two-fold increase in comet tail moment of both lymphocytes and GM cells. Curcumin at 10, 25, and 50 microM also damaged DNA of both types of cells in a dose-dependent manner: the increase in the tail moment reached about twenty times of the control value (P < 0.001). The combined action of chromium at 500 microM and curcumin at 50 microM resulted in the significant (P < 0.001) increase in the comet tail moment of both types of cells. In each case, treated cells were able to recover within 60 min. Our study clearly demonstrates that curcumin does not inhibit DNA damaging action of hexavalent chromium in human lymphocytes and GM cells. Moreover, curcumin itself can damage DNA of these cells and the total effect of chromium and curcumin is additive. Further studies are needed to establish the role of interaction of curcumin with DNA in carcinogenesis.


Cloning of nisin resistance determinant and replication origin on 7.6-kilobase EcoRI fragment of pNP40 from Streptococcus lactis subsp. diacetylactis DRC3.
The nisin resistance determinant and an origin of replication on pNP40, a plasmid of about 60 kilobases that is present in Streptococcus lactis subsp. diacetylactis DRC3, was cloned on a 7.6-kilobase EcoRI fragment. When self-ligated, this fragment existed as an independent replicon (pFM011) and contained a 2.6-kilobase EcoRI-XbaI fragment encoding nisin resistance.


Excessive release of inorganic polyphosphate by ALS/FTD astrocytes causes non-cell-autonomous toxicity to motoneurons.
Non-cell-autonomous mechanisms contribute to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), in which astrocytes release unidentified factors that are toxic to motoneurons (MNs). We report here that mouse and patient iPSC-derived astrocytes with diverse ALS/FTD-linked mutations (SOD1, TARDBP, and C9ORF72) display elevated levels of intracellular inorganic polyphosphate (polyP), a ubiquitous, negatively charged biopolymer. PolyP levels are also increased in astrocyte-conditioned media (ACM) from ALS/FTD astrocytes. ACM-mediated MN death is prevented by degrading or neutralizing polyP in ALS/FTD astrocytes or ACM. Studies further reveal that postmortem familial and sporadic ALS spinal cord sections display enriched polyP staining signals and that ALS cerebrospinal fluid (CSF) exhibits increased polyP concentrations. Our in vitro results establish excessive astrocyte-derived polyP as a critical factor in non-cell-autonomous MN degeneration and a potential therapeutic target for ALS/FTD. The CSF data indicate that polyP might serve as a new biomarker for ALS/FTD.


Epigenetic Mechanisms Underlying the Aging of Articular Cartilage and Osteoarthritis.
Aging is a progressive and complicated bioprocess with overall decline in physiological function. Osteoarthritis (OA) is the most common joint disease in middle-aged and older populations. Since the prevalence of OA increases with age and breakdown of articular cartilage is its major hallmark, OA has long been thought of as "wear and tear" of joint cartilage. Nevertheless, recent studies have revealed that changes in the chondrocyte function and matrix components may reduce the material properties of articular cartilage and predispose the joint to OA. The aberrant gene expression in aging articular cartilage that is regulated by various epigenetic mechanisms plays an important role in age-related OA pathogenesis. This review begins with an introduction to the current understanding of epigenetic mechanisms, followed by mechanistic studies on the aging of joint tissues, epigenetic regulation of age-dependent gene expression in articular cartilage, and the significance of epigenetic mechanisms in OA pathogenesis. Our recent findings on age-dependent expression of 2 transcription factors, nuclear factor of activated T cell 1 (NFAT1) and SOX9, and their roles in the formation and aging of articular cartilage are summarized in the review. Chondrocyte dysfunction in aged mice, which is mediated by epigenetically regulated spontaneous reduction of NFAT1 expression in articular cartilage, is highlighted as an important advance in epigenetics and cartilage aging. Potential therapeutic strategies for age-related cartilage degeneration and OA using epigenetic molecular tools are discussed at the end.


A PDE6A promoter fragment directs transcription predominantly in the photoreceptor.
Rod photoreceptor cGMP phosphodiesterase (PDE6) is a key enzyme in the phototransduction cascade. Lines of transgenic mice were established to determine the spatial expression pattern directed by an upstream fragment of the PDE6A gene. RT-PCR analysis showed that three of four lines analyzed transcribed the transgene predominantly in the retina and weakly in brain. The line showing no transgene transcription did not contain an intact transgene. Transcription of the transgene in the three lines was found in retina and weakly in brain, but not in heart, kidney, liver, or lung. Transcripts were most predominant in the photoreceptors of the retina. These results demonstrate that a short segment of the upstream region of the PDE6A gene comprises a functional promoter that is most active in photoreceptors.


Antiplasmodial activities of sesquiterpene lactones from Eupatorium semialatum.
Eupatorium semialatum, Plasmodium falciparum, Sesquiterpene Lactones Eupatorium semialatum is a member of the Asteraceae, which occurs in Guatemala. Previously, we reported the occurrence of sesquiterpene lactones of the eudesmanolide type as main constituents in the leaves. This paper deals with the isolation and identification of the first guaianolide found in E. semialatum. Since this plant is used against malaria and other diseases in the Guatemalan folk medicine, the main sesquiterpene lactones were tested for their activities against Plasmodium falciparum in vitro.


Clostridium difficile infection and inflammatory bowel disease.
The importance of Clostridium difficile (C. difficile) infection amongst patients with inflammatory bowel disease (IBD) is increasingly being recognized. Recent studies have demonstrated a concerning trend towards increased rates of infection, morbidity, mortality and health costs, and guidelines now promote testing for C. difficile in IBD patients experiencing a relapse. This critical review focuses on the epidemiology, risk factors, pathogenesis, treatment options and outcomes associated with C. difficile infection in patients with IBD.


Non-gastric effects of H. pylori infection: a literature review with respect to non gastric diseases which might be associated with H. pylori infection.
Helicobacter pylori (H. pylori) is the most common cause of peptic ulcers, and is considered as carcinogenic with respect to gastric cancer and MALT lymphoma. The role of H. pylori in other gastroduodenal diseases like atrophic gastritis and functional dyspepsia has been investigated in hundreds of works, but little is done about what role H. pylori may play in non gastric diseases. Gastro-esophageal reflux disease does not seem to be related to H. pylori but Barrett's esophagus might be. Inflammatory bowel diseases tend to be reverse correlated with H. pylori. In coronary heart disease some studies have shown a connection, others not. Diabetes is not likely to be H. pylori-associated and nor do liver diseases with exception for cirrhosis, where a correlation is possible. Respiratory diseases are little examined but bronchiectasis might have a correlation with H. pylori. A small series of children, who had died in sudden infant death, showed a high rate of H. pylori infection.


Monitoring Student Activities with Smartwatches: On the Academic Performance Enhancement.
Motivated by the importance of studying the relationship between habits of students and their academic performance, daily activities of undergraduate participants have been tracked with smartwatches and smartphones. Smartwatches collect data together with an Android application that interacts with the users who provide the labeling of their own activities. The tracked activities include eating, running, sleeping, classroom-session, exam, job, homework, transportation, watching TV-Series, and reading. The collected data were stored in a server for activity recognition with supervised machine learning algorithms. The methodology for the concept proof includes the extraction of features with the discrete wavelet transform from gyroscope and accelerometer signals to improve the classification accuracy. The results of activity recognition with Random Forest were satisfactory (86.9%) and support the relationship between smartwatch sensor signals and daily-living activities of students which opens the possibility for developing future experiments with automatic activity-labeling, and so forth to facilitate activity pattern recognition to propose a recommendation system to enhance the academic performance of each student.


Is robot-assisted gait training intensity a determinant of functional recovery early after stroke? A pragmatic observational study of clinical care.
Gait rehabilitation is a critical factor in functional recovery after a stroke. The aim of this pragmatic observational study was to identify the optimal dose and timing of robot-assisted gait training (RAGT) that can lead to a favourable outcome in a sample of subacute stroke survivors. Subacute patients with stroke who underwent a RAGT within a multidisciplinary rehabilitation program were enrolled. A set of clinical (i.e. age, type of stroke and time since stroke) and rehabilitation stay outcomes (length of stay and RAGT number of sessions) were recorded to evaluate their impact on functional outcome measures by functional independence measure (FIM) or functional ambulation category (FAC). We included 236 patients (62.73 ± 11.82 year old); 38.44% were females, and 59.32% were ischaemic stroke patients. Patients that received at least 14 RAGT sessions, had 15.83% more chance to be responders compared to those that receive less sessions (P = 0.006). Similarly, younger patients (≤60 years) were more prone to be responders (+15.1%). Lastly, an early rehabilitation (<6 weeks) was found to be more efficient (+21.09%) in determining responsiveness (P < 0.001). Becoming newly independent for gait, that refers to a FAC score ≥4, was related with age and RAGT sessions (P = 0.001). In conclusion, a younger age (≤60 years), an early rehabilitation (<6 weeks since stroke) and a higher RAGT dose (at least 14 sessions) were related to a favourable outcome in patients with subacute stroke.


Fluorescence Imaging in Genipin Crosslinked Chitosan⁻Poly(vinyl pyrrolidone) Hydrogels.
Recent research has identified genipin as a promising natural crosslinking agent for biocompatible hydrogels as genipin is significantly less cytotoxic than current synthetic crosslinking agents, such as glutaraldehyde. Conveniently, fluorophores can be produced when genipin crosslinks. In this study, fluorescence intensity measurements of genipin crosslinked chitosan-poly(vinyl pyrrolidone) hydrogels have been explored as a dynamic, in situ method for tracing sol-gel transition. These pH-responsive smart materials have a future in medical applications, in particular in tissue engineering and drug delivery, where methods to follow the process in situ and in real-time are crucial for future advancement. Samples were prepared using deionised water, pH 4, and pH 10 solutions, and studied at 24 and 37 °C over a 24 h period. Both temperature and pH have been found to affect sol-gel transition in the hydrogels studied. The transition from acidic (pH 4) to basic (pH 10) solution resulted in reduced fluorescence intensity suggesting that, under more basic conditions, genipin molecules self-polymerise, reducing the number of molecules available for reaction with the amino groups of chitosan. Three-dimensional representations of the fluorescence present in a hydrogel sample have also been produced from the data, enabling the visualisation of variation in fluorescence with time at the surface of the hydrogel.


An Inflammatory Pseudotumor Arising from Pterygopalatine Fossa with Invasion to the Maxillary Sinus and Orbital Cavity.
We report a patient who had an inflammatory pseudotumor (IPT) that invaded to the maxillary sinus and orbital cavity, with the left pterygopalatine fossa as the principal site; this is a very rare case. The patient was an 83-year-old woman who suddenly became aware of impairment in the eyesight and visual field of the left eye. CT images showed a neoplastic lesion that invaded to the maxillary sinus and orbital cavity, with the left pterygopalatine fossa as the principal site, and also showed contrast effects. To obtain a definitive diagnosis from histopathological analysis, the lesion was biopsied, and she was diagnosed as the inflammatory pseudotumor with the immunohistochemical study and multiplex polymerase chain reaction-based clonality assays. The patient had a lymphoid-predominant lesion that responded to radiotherapy but corticosteroids were not effective. It is important to scrutinize the pathology to avoid unnecessary and mutilating surgery.


How does G-CSF act on the kidney during acute tubular injury?
Recent findings in stem cell research have demonstrated multi-lineage plasticity of bone marrow cells, and also the contribution of hematopoietic bone marrow stem cells to the regeneration of injured organs including the kidney. These findings suggested the possibility of the use of granulocyte colony-stimulating factor (G-CSF) as a therapeutic option to regenerate injured organs. Recently, several studies regarding the effect of G-CSF on renal function have been reported in mouse models of acute renal failure. This series of experiments provided potentially important information regarding the treatment of patients with renal injury. This review summarizes the possible actions of G-CSF on the kidney, especially during acute tubular injury caused by toxic or ischemic insults.


Modest Offset Difference Internuclear Selective Transfer via Homonuclear Dipolar Coupling.
Homonuclear dipolar recoupling is routinely used for magic-angle spinning NMR-based structure determination. In fully protonated samples, only short proton-proton distances are accessible to broadband recoupling approaches because of high proton density. Selective methods allow detection of longer distances by directing polarization to a subset of spins. Here we introduce the selective pulse sequence MODIST, which recouples spins that have a modest chemical shift offset difference, and demonstrate it to selectively record correlations between amide protons. The sequence was selected for good retention of total signal, leading to up to twice the intensity for proton-proton correlations compared with other selective methods. The sequence is effective across a range of spinning conditions and magnetic fields, here tested at 55.555 and 100 kHz magic-angle spinning and at proton Larmor frequencies from 600 to 1200 MHz. For influenza A M2 in lipid bilayers, cross-peaks characteristic of a helical conformation are observed.


Antioxidant Capacity In Vitro and In Vivo of Various Ecotypes of Mexican Plum (Spondias purpurea L.).
Spondias purpurea L. is a fruit native to Mexico, however, it is found as far away as Brazil. It possesses a high commercial potential owing to its sensorial and nutritional qualities and its low cost of production. There exists a variety of ecotypes that have not been characterized and their adequate selection process, according to their strongest functional characteristics, will allow the establishment of improvement programs for this genetic resource. The object of this study was the chemical characterization and the determination of the in vitro and in vivo antioxidant capacity of 7 Spondias purpurea L. ecotypes. Differences were observed in the antioxidant capacity and the content of functional compounds among all the ecotypes analyzed. A high total phenolic content and a low flavonoid and carotenoid content were found, both in the epicarp and in the pulp. In each ecotype, the hydrophilic phase presented up to 40 times greater antioxidant capacity compared to the lipophilic phase. The hydrophilic phase of the epicarp of "Costeña Tierra Colorada" had the greatest antioxidant capacity and highest total phenolic content, whereas "Jocote" presented the lowest antioxidant capacity and total phenolic content. A positive correlation was observed between phenol levels and the antioxidant capacity in the epicarp. Regarding antioxidant activity in vivo, it was observed that in all analyzed concentrations of hydrophilic extracts of the epicarp of "Costeña Tierra Colorada" and in the highest "Jocote" concentrations, they provided thermo-protection against heat stress as well as a general well-being to the worm as evidenced by their high mobility.


Effects of diabetes, insulin and antioxidants on NO synthase abundance and NO interaction with reactive oxygen species.
Earlier studies have provided evidence for increased production of reactive oxygen species (ROS) and altered nitric oxide (NO) metabolism in diabetes. This study was intended to explore the effect of type I diabetes and its treatment with insulin alone or insulin plus antioxidant-fortified diet on expression of NOS isoforms and ROS interactions with lipids, glucose and NO. Rats with streptozotocin-induced diabetes were divided into once-daily insulin (ultralente)-treated, insulin plus antioxidant (vitamin E and vitamin C)-treated and untreated groups. After four weeks, plasma malondialdehyde (MDA) and tissue endothelial (eNOS), neuronal (nNOS) NO synthases, carboxymethyllysine (CML) and nitrotyrosine were determined. The untreated diabetic animals exhibited severe hyperglycemia, elevated blood pressure, increased plasma MDA, high tissue CML and reduced tissue nitrotyrosine denoting enhanced lipid, glucose and protein oxidation but reduced NO oxidation by ROS. This was coupled with significant reduction of eNOS and nNOS expression in renal cortex and eNOS in the left ventricle. Insulin therapy partially lowered blood pressure, tissue CML, plasma glucose and MDA, but significantly raised eNOS expression and nitrotyrosine abundance to supranormal levels. Combined insulin and antioxidant therapies resulted in normalization of blood pressure, plasma MDA, tissue CML and nitrotyrosine without affecting glucose level or NOS expression. Oxidative stress in untreated diabetes is associated with down-regulation of NOS isoforms and increased ROS-mediated oxidation of lipid and glucose, but not NO. Amelioration of hyperglycemia with once-daily insulin administration alone results in up-regulation of NOS isoforms, reduction of lipid and glucose oxidation and increased NO oxidation. However, insulin plus antioxidant supplementation can normalize all three parameters.


The Association between Neutrophil-to-Lymphocyte Ratio and Diabetic Depression in U.S. Adults with Diabetes: Findings from the 2009-2016 National Health and Nutrition Examination Survey (NHANES).
To determine the association between neutrophil-to-lymphocyte ratio (NLR) and clinically relevant depressive symptoms in people with diabetes. This cross-sectional study was conducted among adults (age >18) with diabetes in the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2016. NLR was calculated from complete blood count. Nine-item Patient Health Questionnaire (PHQ-9) was used to measure depression, with scores ≥10 indicating the presence of clinically relevant symptoms. Multivariable logistic regression was used to calculate the odds ratio (OR) with 95% confidence interval (CI) of clinically relevant depressive symptoms in relation to the NLR. We performed the smooth curve fitting and established a weighted generalized additive model to identify the nonlinearity of NLR and depression in diabetes patients. To account for the nonlinear relationship between NLR and depression in diabetes patients, weighted two-piecewise linear model was applied. We included 2,820 eligible participants, of which 371 (12.4%) had clinically relevant depressive symptoms. In the unadjusted model, the OR (95% CI) of clinically relevant depressive symptoms for the second (NLR 1.75-2.57) and third (NLR >2.57) were 1.24 (0.90, 1.70) and 1.68 (1.23, 2.30), respectively, compared to the reference group (NLR < 1.75). After controlling for potential confounding factors, NLR was significantly associated with clinically relevant symptoms (odds ratio = 1.57, 95% confidence interval: 1.13-1.87; P for trend = .0078). Nonlinear relationships were observed, and a two-piecewise linear regression model was established. The inflection point of NLR was 2.87. To the left of the inflection point (NLR ≤ 2.87), the OR (95% CIs) was 1.33 (1.07-1.66) (P < .031). Elevated levels of NLR are independently associated with increased odds of clinically relevant depressive symptoms in people with diabetes. Prospective study is needed to further analyze the role of NLR in depression in diabetic patients.


Self-expanding metallic stents in the management of lower gastrointestinal hemorrhage.
A case of an 82-year-old woman is reported who developed a lower gastrointestinal hemorrhage secondary to metastatic ovarian carcinoma to the colon. The bleeding, associated with an incomplete obstruction of the large bowel, was successfully treated with the endoscopic insertion of two self-expanding metal stents. A technique of stent placement is presented which differs from that previously reported, where both stents were via colonoscopy and without the use of fluoroscopy.


How to detect and reduce potential sources of biases in studies of SARS-CoV-2 and COVID-19.
In response to the coronavirus disease (COVID-19) pandemic, public health scientists have produced a large and rapidly expanding body of literature that aims to answer critical questions, such as the proportion of the population in a geographic area that has been infected; the transmissibility of the virus and factors associated with high infectiousness or susceptibility to infection; which groups are the most at risk of infection, morbidity and mortality; and the degree to which antibodies confer protection to re-infection. Observational studies are subject to a number of different biases, including confounding, selection bias, and measurement error, that may threaten their validity or influence the interpretation of their results. To assist in the critical evaluation of a vast body of literature and contribute to future study design, we outline and propose solutions to biases that can occur across different categories of observational studies of COVID-19. We consider potential biases that could occur in five categories of studies: (1) cross-sectional seroprevalence, (2) longitudinal seroprotection, (3) risk factor studies to inform interventions, (4) studies to estimate the secondary attack rate, and (5) studies that use secondary attack rates to make inferences about infectiousness and susceptibility.


Testing the validity of the Euroqol and comparing it with the SF-36 health survey questionnaire.
There is an interest in the consequences of deriving a single index measure of health for validity and sensitivity. This paper presents the results of testing a recent example of a general health measure designed to derive a single index, the Euroqol (EQ), and presents a comparison with a new, influential profile measure, the Short Form 36 (SF-36) Health Survey Instrument. The EQ and an anglicised version of the SF-36 health survey, both designed for self-completion, were included in a postal survey of a random sample of 1980 patients from two practice lists in Sheffield, UK. The response rate for the EQ questionnaire was 83%, and the rate of completion over 95%. Evidence was found for the construct validity of the EQ dimension responses and the derived total EQ health score in terms of distinguishing between groups with expected health differences. Considerable agreement was found between EQ responses and the total EQ score, and the UK SF-36 profile scores. There was substantial evidence of EQ being less sensitive at the ceiling (i.e. low levels of perceived ill-health) and throughout the range of health states. A recent restructuring of the EQ, may help overcome some of the problems with the physical dimensions by reducing their skewness.


Bring Your Own Device and Nurse Managers' Decision Making.
The Bring Your Own Device phenomenon is important in the healthcare environment because this trend is changing the workplace in healthcare organizations, such as British Columbia. At present, there is little research that exists in Canada to provide a distinct understanding of the complexities and difficulties unique to this phenomenon within the nursing practice. This study focused on the experiences and perceptions of nurse managers regarding how they make decisions on the use of personal handheld devices in the workplace. Telephone interviews (N = 10) and qualitative descriptive analysis were used. Four major themes emerged: (1) management perspective, (2) opportunities, (3) disadvantages, and (4) solutions. Nurse managers and other executives in healthcare organizations and health information technology departments need to be aware of the practice and organizational implications of the Bring Your Own Device movement.


Primary erythromelalgia mainly manifested by hypertensive crisis: A case report and literature review.
Primary erythrocytic (PEM) is a rare autosomal dominant single gene disease. Most of the changes of gene loci can be found by whole exon gene sequencing, and the clinical symptoms and patient survival can be improved by specific site-to-site drug treatment. The other manifestations of this patient population are not remarkable. After the application of common drugs, the toxicity and side effects can be limiting. In addition to other common clinical manifestations, we found that the only unique manifestation of this patient was hypertensive crisis. Following multidisciplinary diagnosis and treatment (MDT), we decided to first control hypertension to alleviate the acute and critical patients. However, after controlling the hypertensive crisis, we unexpectedly found that the clinical symptoms of the patients had been significantly improved. Therefore, we concluded that the use of antihypertensive drugs can treat erythematous limb pain with the clinical manifestation of hypertensive crisis. Here, we describe a typical PEM disease, primary clinical features, diagnosis and treatment. Medical records of an 8-year-old boy with PEM were analyzed retrospectively, which included clinical characteristics, follow-up information, and SCN9A (Sodium Voltage-Gated Channel Alpha Subunit 9) gene analysis. The 8-year-old boy had complained of abnormal paresthesia in his feet and ankles with burning sensation and pain for 2 years. The skin of both lower legs was red and underwent ichthyosis and lichenification. Genetic analysis confirmed the existence of a SCN9A gene mutation. The symptoms were gradually improved by treating with intravenous drip and oral administration of nitroglycerin to slow his heart rhythm. Primary erythrocytic is characterized by skin ulceration, redness, elevated temperature, and severe burning pain primarily in both lower extremities. PEM can be diagnosed by genetic analysis. As this case demonstrates, treating with nitroglycerin as the drug of choice to control the hypertensive crisis significantly improved the symptoms of PEM and hypertension in this patient.


RNA interference as a gene silencing therapy for mutant MYOC protein in primary open angle glaucoma.
Primary open-angle glaucoma (POAG) is the most common form of glaucoma which is an irreversible blind leading disease and lacks effective remedies. In recent years, POAG has been linked to the gene MYOC encoding myocilin that has been identified to harbor causal mutations. A variety of studies show that the mutant myocilin acts by gain of function. The mutant MYOC protein induces endoplasmic reticulum (ER) stress and the resultant unfolded protein response (UPR) induces apoptosis in the trabecular meshwork cells, which then leads to an increase in resistance to aqueous humor outflow, elevated intraocular pressure (IOP), and, ultimately, glaucoma. Culturing human trabecular meshwork (HTM) cells at a condition facilitating protein folding promotes secretion of mutant myocilin, normalizes cell morphology and reverses cell lethality. We speculate that a complete elimination of mutant myocilin expression in trabecular meshwork cells is safe and that gives the possibility of avoiding the POAG phenotype. We propose RNA interference (RNAi) as a gene silencing therapy to eliminate the mutant myocilin proteins in the trabecular meshwork cells, either in a mutation-dependent or mutation-independent way due to the different engineering of the small interfering (si) RNA. The RNAi strategy can reverse the pathological process of trabecular meshwork cells and thus treat the POAG caused by myocilin gene mutation. This strategy can also be applicable to many protein-misfolding diseases caused by gain-of-function mutant proteins.


Recent advances in targeted nanotherapeutic approaches for breast cancer management.
Breast cancer is the most commonly occurring tumor disease worldwide. Breast cancer is currently managed by conventional chemotherapy, which is inadequate in curbing this heterogeneous disease and results in off-site toxic effects, suggesting effective treatment approaches with better therapeutic profiles are needed. This review, therefore, focuses on the recent advancements in delivering therapeutics to the target site using passive and/or active targeted nanodrug-delivery systems to ameliorate endolysosomal escape. In addition, recent strategies in targeting breast cancer stem cells are discussed. The role of naturally cell-secreted nanovesicles (exosomes) in the management of triple-negative breast cancer is also discussed.


A dual blood supply protects the right gastroepiploic arterial graft: report of two cases.
We report two cases whose right gastroepiploic arterial bypass grafts were protected by a dual blood supply due to the anatomical anastomosis between the celiac and the superior mesenteric artery systems. This unique characteristic of the graft adds an advantage for its use as a graft conduit.


Buccal bifurcation cyst (paradental cyst) defined by ultrasonography and cone-beam computed tomography.
Buccal bifurcation cyst (BBC) is an uncommon inflammatory odontogenic cyst that generally occurs at the buccal region of the permanent mandibular first molars in children aged 6-8 years. The diagnosis of BBC cannot be made from the histopathologic features; therefore, diagnosis is primarily based on specific clinical and radiographic findings. In this case report, we present the clinical and radiological findings, including ultrasonography (USG) and cone-beam computed tomography (CBCT) images, of a 10-year-old boy who was referred with a complaint of swelling on the lower right jaw. According to the radiographic and clinical findings, the differential diagnosis of this lesion included lateral radicular cyst, lateral periodontal cyst, dentigerous cyst, eruption cyst, and others. Recently, in addition to classical radiographies and CBCT, USG has been considered important for diagnosis. In particular, if a cyst produces a perforation in the cortical bone, it is helpful to make a pre-diagnosis with USG.


Development and validation of a ligand-binding assay for quantification of the F(ab')2 antivenom of Daboia russelii siamensis in human serum and its application to a phase I clinical study.
Daboia russelii siamensis accounts for most of snakebite mortalities in China, yet, specific treatment against the venom toxins is absent in clinical practice. The F(ab')2 antivenom of Daboia russelii siamensis is manufactured and approved for the clinical trial in China. To satisfy the need for clinical pharmacokinetic research, this study aimed to develop a ligand binding assay (LBA) for the quantification of F(ab')2 antivenom of Daboia russelii siamensis in human serum. A diverse combination of conditions was optimized based on the fitness of the calibration curve and selectivity. The established LBA undergoes thorough method validation according to the guidelines of regulatory authorities. In the calibration range 1.0-64 μg/mL, the correlation coefficient r2 was from 0.9970 to 1.000, indicating good fitness. Accuracy and precision were within ± 20%. Dilution linearity was observed in the ultra-high quality-control (QC) samples (500 μg/mL). In addition, the assay was free from hook effect, the endogenous interferences and exogenous interferences. The QC samples were stable under different handling and storage conditions. The validated assay was successfully applied to a phase I clinical study of the F(ab')2 antivenom of Daboia russelii siamensis in Chinese healthy volunteers. The peak concentrations exhibited dose-proportionality. In conclusion, this study provides a novel and reliable LBA method for the clinical pharmacokinetic research of F(ab')2 antivenom of Daboia russelii siamensis. It will facilitate further clinical trials in treating the snakebite of Daboia russelii siamensis.


SRD5A1 genotype frequency differences in women with mild versus severe premenstrual symptoms.
The aims of this small pilot study were to explore the association between premenstrual symptom severity and two genes from the gamma-aminobutyric acid (GABA) pathway: steroid-5-alpha-reductase, alpha polypeptide 1 (SRD5A1) and gamma-aminobutyric acid receptor subunit alpha-4 (GABRA4). Saliva samples were obtained from a convenience sample of 19 Caucasian females ages 18-25 years, ten cases and nine controls. Deoxyribonucleic acid (DNA) was isolated, and genotyping performed on ten single nucleotide polymorphisms (SNPs). Ten percent of cases and 44% of controls had the cytosine/cytosine (C/C) genotype for the SRD5A1 SNP, rs501999 indicating that this genotype may protect women against severe premenstrual symptoms. Replication of this study using an adequately powered sample size is warranted.


The rat costo-uterine muscle: a preparation of smooth muscle containing a homogeneous population of beta-adrenoreceptors.
This paper describes some histological features of the costo-uterine muscle of the rat together with the effects of some sympathomimetic amines upon contractions evoked by field electrical stimulation of isolated preparations. Light and electron microscopy confirmed that the costo-uterine muscle of the rat consists of smooth muscle bundles, arranged longitudinally and interspersed with collagen. There were close contacts between individual cells within bundles. No axon profiles were observed. Histochemical techniques revealed only sparse catecholamine fluorescence at the border of the tissue in association with blood vessels. Isoprenaline, fenoterol, adrenaline, noradrenaline, salbutamol and phenylephrine consistently inhibited contractions evoked by field stimulation (40V, 30Hz, 2 ms for 5 sec every 200 sec). In contrast, tyramine was without effect upon electrically evoked contractions in concentrations of up to 200 mumol/l. The slopes of the log concentration-response curves of effective amines were similar, and all of these were capable of producing 100% inhibition of contraction. The potencies of the amines relative to isoprenaline = 100 were: fenoterol 135; salbutamol 16; adrenaline 16; noradrenaline 0.7; phenylephrine 0.1; tyramine less than 0.001. Propranolol, added to preparations in the absence of inhibitors of amine uptake and alpha-adrenoreceptors, competitively antagonised the effects of the amines. Schild plots had slopes which did not differ significantly from minus one, and the mean pA2 values fell within a narrow range, e.g. 8.65 with salbutamol; 9.20 with fenoterol. Mean pA2 values for propranolol with noradrenaline and isoprenaline were unaffected by the combined presence of phentolamine (10 mumol/l), cocaine (10 mumol/l), and corticosterone (10 mumol/l). The potencies of the agonists were also unaffected by the presence of these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)


Quantification of polyphenols during retting and characterization of bacteria from the Kadinamkulam Backwaters, Kerala.
The retting environment which provides a competitive niche for specialized microbes is speculated to harbour a variety of microbes with high biodegradation potential. In this context, an effort has been made to isolate and identify bacterial species having high tolerance to phenol In vitro. Maximum polyphenol (1.897 mg l(-1)) as observed during the initial period of retting, which decreased as retting proceeded. Based on biochemical characterization, the isolated bacterial strains were identified as Micrococcus sp., Moraxella sp. strain MP1, Moraxella sp. strain MP2 and Moraxella sp. strain MP3, Pseudomonas sp. strain PP1 and Pseudomonas sp. strain PP2, Amphibacillus sp., Brucella sp. strain BP1 and Brucella sp. strain BP2, Aquaspirillum sp., Escherichia coli strain EP1 and Escherichia coli strain EP2, Campylobacter sp., Aeromonas sp., Neisseria sp., Vibrio sp., Erwinia sp. and Mesophilobacter sp. These strains were found to tolerate maximum concentration of phenol viz. 200 to 1000 mg l(-1). Plasmid analysis of phenol resistant bacterial isolates showed that almost all the cultures had at least one plasmid of size > 1Kb. Studies on the protein profile of isolated bacterial cultures showed the presence of proteins with molecular sizes ranging from 10 to 85 KDa with exception of Mesophilobacter and Neisseria having still high molecular weight protein (95 KDa). Bacterial strains isolated from coir-ret-liquor showed tolerance to high phenol concentration.


Allele frequency distribution of CYP2C19*2 allelic variants associated with clopidogrel resistance in cardiac patients.
Drug resistance is a phenomenon that has become a critical issue in medical practice. Such is the case in the response to clopidogrel treatment, which is variable inter-individually and inter-ethnically due to genetic polymorphisms in the cytochrome P40 (CYP) gene. Clopidogrel is an anti-platelet agent administered to cardiac patients in the form of a prodrug, which is further metabolized into an active form by CYP enzymes. There are many allelic variants of the CYP gene that are involved in clopidogrel resistance, of which CYP2C19*2 has been demonstrated to be one of the most significant loss-of-function alleles. In the present study, 100 cardiac patients with percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS) who were undergoing treatment with clopidogrel were selected and the patients were analyzed for CYP2C19*2 allelic variants using an allele-specific primer extension polymerase chain reaction method. The variant amplicons were visualized on gel and validated by Sanger sequencing. The observed allelic frequency distribution of CYP2C19*2 variants was 18% heterozygous for CYP2C19*2 A/C/G variants, 35% heterozygous for A/G variants, 13% heterozygous for C/G variants, 6% heterozygous for A/C variants, 7% homozygous for A variant, 5% homozygous for C variant and 16% homozygous for G wild-type. Furthermore, tri-allelic single nucleotide polymorphisms (SNPs) were identified in the CYP2C19*2 allele in cardiac patients for the first time, to the best of our knowledge; these were CYP2C19*2 A/C/G SNPs (18%). The overall frequency observed for new allelic variant C of CYP2C19*2 was 42%. These results suggested that there are significant inter-ethnic variations in the allelic frequencies of CYP2C19*2, which may be responsible for the variable clopidogrel response in cardiac patients.


Optimizing expression and purification of an ATP-binding gene gsiA from Escherichia coli k-12 by using GFP fusion.
The cloning, expression and purification of the glutathione (sulfur) import system ATP-binding protein (gsiA) was carried out. The coding sequence of Escherichia coli gsiA, which encodes the ATP-binding protein of a glutathione importer, was amplified by PCR, and then inserted into a prokaryotic expression vector pWaldo-GFPe harboring green fluorescent protein (GFP) reporter gene. The resulting recombinant plasmid pWaldo-GFP-GsiA was transformed into various E. coli strains, and expression conditions were optimized. The effect of five E. coli expression strains on the production of the recombinant gsiA protein was evaluated. E. coli BL21 (DE3) was found to be the most productive strain for GsiA-GFP fusion-protein expression, most of which was insoluble fraction. However, results from in-gel and Western blot analysis suggested that expression of recombinant GsiA in Rosetta (DE3) provides an efficient source in soluble form. By using GFP as reporter, the most suitable host strain was conveniently obtained, whereby optimizing conditions for overexpression and purification of the proteins for further functional and structural studies, became, not only less laborious, but also time-saving.


Echocardiographic image tracker with a speckle adaptive noise reduction filter for the automatic measurement of the left atrial volume curve.
Since tracking accuracy in left atrial (LA) images decreases due to low image quality around the LA in the apical view, a practical tracking method for LA images has not yet been proposed. The aim of this study was to assess an accurate and high-speed LA volume tracking (LAVT) method for the automatic measurement of LA volume (LAV) curves. We used three approved protocols in this study: (i) LAV curves were measured by LAVT on computer-simulated images; (ii) in 20 healthy volunteers, we assessed the feasibility and accuracy of this method compared with expert's measurements; and (iii) echocardiography and multi-detector row computed tomography (MDCT) imaging were performed on the same day in 20 patients with suspected coronary artery disease. On computer-simulated images, mean absolute percentage LAVT error in one cardiac cycle was 3% in filtered images and 16% in original images. In 20 healthy volunteers, there are strong correlations between LAVT and the expert's LA measurements (LA maximum volume; R = 0.93, P < 0.001). In 400 LA images with 20 patients, an excellent correlation was obtained between LAVs using echocardiography and MDCT (R = 0.98, P < 0.001), with a small bias (-14% of the mean) and narrow limits of agreement (+15% of the mean). The mean time required for the LAVT analysis was 1.8 min, for the MDCT analysis was 35.8 min, and for the manual echocardiographic analysis was 14.0 min. This LAVT method is fast, valid, accurate, and reproducible for determining LAV in both simulated images and the clinical setting.


Clinical investigation of the Paraperm EW rigid gas-permeable contact lens.
Paraperm EW is a high oxygen flux silicone/acrylate rigid lens material currently under clinical investigation for extended wear. The purpose of this paper is to report the clinical findings after 12 months of a 2-year investigation of 18 patients fitted with this material. Fifteen were successfully wearing Paraperm EW lenses at 1 year. The only significant clinical finding was keratometric flattening at the 1-month visit. It was concluded that the Paraperm EW lens was durable, comfortable, and provided excellent visual acuity during the course of this investigation without inducing any of the ocular complications sometimes associated with extended wear of hydrogel lenses.


Exploring the mechanisms underlying the therapeutic effect of Salvia miltiorrhiza in diabetic nephropathy using network pharmacology and molecular docking.
The mechanisms underlying the therapeutic effect of Salvia miltiorrhiza (SM) on diabetic nephropathy (DN) were examined using a systematic network pharmacology approach and molecular docking. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen active ingredients of SM. Targets were obtained using the SwissTargetPrediction and TCMSP databases. Proteins related to DN were retrieved from the GeneCards and DisGeNET databases. A protein-protein interaction (PPI) network was constructed using common SM/DN targets in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The Metascape platform was used for Gene Ontology (GO) function analysis, and the Cytoscape plug-in ClueGO was used for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was performed using iGEMDOCK and AutoDock Vina software. Pymol and LigPlos were used for network mapping. Sixty-six active ingredients and 189 targets of SM were found. Sixty-four targets overlapped with DN-related proteins. The PPI network revealed that AKT serine/threonine kinase 1 (AKT1), VEGFA, interleukin 6 (IL6), TNF, mitogen-activated protein kinase 1 (MAPK1), tumor protein p53 (TP53), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 14 (MAPK14), and JUN were the ten most relevant targets. GO and KEGG analyses revealed that the common targets of DN and SM were mainly involved in advanced glycation end-products, oxidative stress, inflammatory response, and immune regulation. Molecular docking revealed that potential DN-related targets, including tumor necrosis factor (TNF), NOS2, and AKT1, more stably bound with salvianolic acid B than with tanshinone IIA. In conclusion, the present study revealed the active components and potential molecular therapeutic mechanisms of SM in DN and provides a reference for the wide application of SM in clinically managing DN.


Bi-level evolutionary graphs with multi-fitness.
Evolutionary graphs (EGs) were initially introduced in 2005 and give an outlet for the evolutionary dynamic determined by the population structures, the fitness of the mutants and the number of the individuals. Bi-level EGs with different fitness are discussed. The corresponding fixation probability is given, especially when the lower level and the upper level are all isothermal. The optimisation fixation probabilities are also built if the lower and the upper graphs are all isothermal structures and the number of the total individuals is finite. At last, some applications to the system biology are involved.


Glucocorticoids enhance the expression of the basolateral Na+:HCO3- cotransporter in renal proximal tubules.
Studies have shown that glucocorticoids enhance HCO3- reabsorption in proximal tubules. Functional and molecular studies indicate that HCO3- reabsorption in proximal tubules is mediated via luminal H(+)-ATPase and Na+/H+ exchanger (NHE-3), and basolateral Na+:HCO3- cotransporter (NBC) acting in series. The purpose of these experiments was to examine the effect of adrenal steroids on NBC-1 and NHE-3 expression and activity in rat renal proximal tubules. Rats were injected subcutaneously with dexamethasone (100 mu/day) or deoxycorticosterone acetate (30 mg/kg), potent glucocorticoid, or mineralocorticoid analogues, respectively. Animals were sacrificed after two or four days, and NBC-1 and NHE-3 mRNA expression and activities were measured in cortex and proximal tubules. Northern hybridizations indicated that cortical NBC-1 mRNA expression increased by approximately 92% in rats treated with dexamethasone for four days (N = 6, P < 0.03) but not two days. NHE-3 mRNA expression remained unchanged. NBC and NHE-3 activities were measured as the Na-dependent pHi recovery from an acid load in the presence or absence of HCO3-, respectively, and appropriate inhibitors in proximal tubule suspensions loaded with BCECF. NBC activity increased by approximately 80% in rats treated with dexamethasone for four days (P < 0.01, N = 5) but not two days. NHE-3 activity increased by 34 and 42% in rats treated with dexamethasone for two and four days, respectively (P < 0.05 and P < 0.02 for each group vs. control). Treatment with deoxycorticosterone acetate did not alter NBC-1 expression. Glucocorticoids at pharmacologic concentrations enhance the mRNA expression and functional activity of renal proximal tubule NBC-1. Enhanced NBC and NHE-3 activities could result in increased HCO3- reabsorption in proximal tubule and could contribute to the maintenance of metabolic alkalosis in pathophysiologic states associated with increased glucocorticoid production.


Organic dust exposure in dairy farmers in an alpine region.
Epidemological studies suggest that farmers are at an increased risk for chronic obstructive pulmonary disease because of exposure to organic dust. We assessed the proportion of farmers among patients with end stage lung disease and we measured the seasonal exposure of dairy farmers to organic dust in a rural alpine region in Switzerland. Six dairy farms of different sizes and infrastructures were chosen for measurements of organic dust (PM10 = particles with a 50% cut-off aerodynamic diameter of 10 gm). Indoor measurements were performed during 3-5 days at each farm in late winter, summer and early winter of one year. 17 measurements of organic dust were carried out on 6 different farms. The concentrations of PM10 ranged from 109-2207 microg/m3 for daily barn activities in winter months and from 76-4862 microg/m3 for hay storage in summertime. Exposure depended on farm infrastructure and season. It was higher in smaller and older cattle buildings and during the late winter months. The farmers were exposed to the measured amount of organic dust (PM10) for 5 to 6 hours per day during the winter (approximately 900-1260 hours/year). The study confirms a moderate to high exposure to organic dust (PM10) in these farmers, which, together with epidemiological data, suggests that such exposure over many years could be a major risk factor for the development of chronic obstructive pulmonary disease in dairy farmers.


Expanding student learning using patient pathways.
This article examines the first stages of a project to address problems in the quality of students' clinical experience after consultation with senior nurses at a large district general hospital. The term 'placement pathway' is defined and the use of these pathways is discussed. Several examples are given to demonstrate ways in which students can gain a wider understanding of the care of the patient throughout their stay and still achieve competence.


Vertically coupled whispering-gallery-mode resonator waveguide.
We theoretically describe a novel configuration of a vertically coupled whispering-gallery-mode resonator waveguide. The waveguide is formed as a chain of doughnut-shaped low-contrast ripples on the surface of a vertical cylinder made from an optically transparent material. One can manipulate the properties of the waveguide by changing the shape of the resonators and the separation distance between them. Application of the structure as an optical delay line is discussed.


The Intradiscal Osteotomy: An Alternative Technique for Adult Spinal Deformity Correction.
Adult spinal deformity (ASD) correction has changed considerably since the initial description of a Smith-Petersen osteotomy (SPO), including pedicle subtraction osteotomies (PSO), and more minimally invasive techniques. Here, we introduce and describe the intradiscal osteotomy (IDO), a novel variation of Schwab type 3 and 4 osteotomies allowing pedicle and vertebral body preservation, and its advantages and disadvantages. After pedicle screw placement, the posterior elements (except pedicles) are removed from the appropriate vertebrae, including the superior/inferior articulating processes, laminae, and spinous processes. An osteotome is used to remove the posterior aspect of the superior and inferior endplate, followed by the entire disc, creating more working room for eventual cage insertion. After the careful release of the annulus, an intradiscal distractor is used to distract the endplates and allow interbody cage insertion as anteriorly as possible. Pedicle and vertebral body preservation allow increased fixation and endplate cage support, which lengthens the anterior column and acts as a fulcrum when compressing posteriorly to restore lordosis. By allowing for anterior and posterior column release, the IDO technique provides a feasible, all-posterior approach for the correction of fixed or flexible kyphoscoliotic curves. This technical report introduces and describes the IDO as an alternative method for thoracic and/or lumbar ASD correction. More studies are required to fully elucidate its outcome vs. complication profile compared to other deformity correction techniques.


Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives.
The concentration of plasma copper, ceruloplasmin (CRP), non-ceruloplasmin-bound Cu (NCBC), and metallothioneins (MTs) were studied as putative biomarkers for neurodegenerative diseases in patients and in their first-degree relatives. We found increased levels of Cu in the plasma of Alzheimer's disease (AD), Parkinson's disease (PD), and vascular dementia (VD) patients, and the increase observed in VD group was linked to the evolution of the disease. CRP was also elevated in response to the inflammatory component of the diseases, however, a correlation with illness progression was only observed in VD patients. The level of MTs is proportional to the evolution of VD. The Cu/CRP and Cu/MTs ratios are both indicative of disease progression for AD patients but not for those with PD or VD. Moreover, there is a correlation between the NCBC levels and the cognitive impairment estimated through the Mini-mental State Examination (MMSE) scale. This dependence is linear for AD and PD patients and non-linear for the VD ones. The relative values of NCBC showed dependence on the disease duration, especially for AD. Copper measurement and the Cu/CRP ratio may be predictive markers of risk for the first-degree relatives of AD patients. We believe that these results are valuable as a reliable clinical tool.


An eighteenth century view of the placebo effect (Rétif de la Bretonne).
Placebo - the promise to please the Lord of medieval prayer became the "pious fraud" (Thomas Jefferson) of late 18th century medical practice. Quoted here is Rétif de la Bretonne (1734-1806), one of the most prolific novelists and popular encyclopedists ever, also highly regarded by some illustrious critics, as he is giving his cynical views about the "prejudices", (rather then "placebos") in religion, politics, and the art of healing.


Protection of erythrocytes from human complement-mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy.
Paroxysmal nocturnal hemoglobinuria (PNH) results from the expansion of a hematopoietic clone that is deficient in glycosylphosphatidylinositol-anchored molecules. PNH is characterized by chronic hemolysis with acute exacerbations due to the uncontrolled activity of complement on PNH cells, which lack the inhibitor of homologous complement, CD59. Symptoms include severe fatigue, hemoglobinuria, esophageal spasm, erectile dysfunction, and thrombosis. We report the use of a novel synthetically modified recombinant human CD59, rhCD59-P, a soluble protein that attaches to cell membranes. In vitro treatment of PNH erythrocytes with rhCD59-P resulted in levels of CD59 equivalent to normal erythrocytes and effectively protected erythrocytes from complement-mediated hemolysis. The administration of rhCD59-P to CD1 mice resulted in levels of CD59 on erythrocytes, which protected them from complement-mediated lysis. Thus, rhCD59-P corrects the CD59 deficiency in vitro and can bind to erythrocytes in an in vivo murine model, protecting the cells from the activity of human complement, and represents a potential therapeutic strategy in PNH.


Biobased Thermoplastic Elastomers: Structure-Property Relationship of Poly(hexamethylene 2,5-furanodicarboxylate)-Block-Poly(tetrahydrofuran) Copolymers Prepared by Melt Polycondensation.
A series of poly(hexamethylene 2,5-furanodicarboxylate)-block-poly(tetrahydrofuran) (PHF-b-F-pTHF) copolymers were synthesized using a two-stage procedure, employing transesterification and polycondensation. The content of pTHF flexible segments varied from 25 to 75 wt.%. 1H nuclear magnetic resonance (NMR) and Fourier transformed infrared spectroscopy (FTIR) analyses were applied to confirm the molecular structure of the materials. Differential scanning calorimetry (DSC), dynamic mechanical measurements (DMTA), and X-ray diffraction (XRD) allowed characterizing the supramolecular structure of the synthesized copolymers. SEM analysis was applied to show the differences in the block copolymers' morphologies concerning their chemical structure. The influence of the number of flexible segments in the copolymers on the phase transition temperatures, thermal properties, as well as the thermo-oxidative and thermal stability was analyzed. TGA analysis, along with tensile tests (static and cyclic), confirmed the utilitarian performance of the synthesized bio-based materials. It was found that an increase in the amount of pTHF caused the increase of both number-average and weight-average molecular weights and intrinsic viscosities, and at the same time causing the shift of the values of phase transition temperatures toward lower ones. Besides, PHF-b-F-pTHF containing 75 wt.% of F-pTHF units was proved to be a promising thermoplastic shape memory polymer (SMP) with a switching temperature of 20 °C.


Identification of strA-strB Genes in Streptomycin-Resistant Pseudomonas syringae pv. actinidiae Biovar 2 Strains Isolated in Korea.
Bacterial canker is a devastating disease of kiwifruit caused by the bacterium Pseudomonas syringe pv. actinidiae. Canker disease of kiwifruit in Korea has been controlled using streptomycin for more than two decades. Four streptomycin-resistant strains, belonging to biovar 2, which are found only in Korea, were collected between 2013 and 2014 from different orchards located in Jeju, Korea. The genetic background for streptomycin resistance among P. syringe pv. actinidiae strains were determined by examining the presence of strA-strB or aadA, which are genes frequently found in streptomycin-resistant bacteria, and a point mutation at codon 43 in the rpsL gene. All four streptomycin-resistant strains of P. syringe pv. actinidiae investigated in this study contained strA-strB as a resistant determinant. The presence of the aadA gene and a mutation in codon 43 of the rpsL gene was not identified.


Laser epithelial keratomileusis for myopia with the autonomous laser.
To describe the refractive outcome, objective clinical data, and subjective patient experiences after laser epithelial keratomileusis (LASEK) at 1, 3, and 6 months after surgery. This was a retrospective, nonrandomized, comparative study of 58 LASEK-treated eyes (36 patients) with myopia (with and without astigmatism) between -1.50 and -14.75 D (mean -7.80 +/- 2.90 D, median -7.90 D). Refractive surgery was performed using the Alcon Summit Autonomous LADAR Vision excimer laser. Manifest refraction, best-spectacle and uncorrected Snellen visual acuity, stability of refraction, and corneal haze were evaluated before surgery and up to 6 months after surgery. A group of randomly selected LASIK-treated eyes were compared at each time point. Patients who opted for monovision (n=12) were excluded. In the emmetropia targeted eyes (n=46), 45%, 83%, 85%, and 89% achieved 20/40 or better uncorrected Snellen visual acuity (UCVA) at 1 day, 1 week, 2 weeks, and 1 month respectively. At 6 months, 73% (n=28) of eyes treated achieved UCVA 20/20 with 97% achieving 20/40 or better (mean, -0.51 D). At 3 and 6 months, 71% (n=46) and 68% (n=28) were within +/- 0.50 D of emmetropia. The percentage of eyes that achieved UCVA 20/40 or better at 6 months was 97% (n=28). Visually significant corneal haze was evident in two LASEK-treated patients (four eyes) at 6 months. No eyes lost two or more lines of best spectacle-corrected Snellen visual acuity. Preliminary data suggest that LASEK appears to be a safe, effective, and comparable alternative to LASIK, even for higher amounts of myopia. A prospective, randomized clinical trial is needed to better define the role of LASEK as it compares to other refractive procedures, specifically LASIK and PRK.