An artificial plastic receptor that discriminates axial asymmetry.
An artificial plastic receptor that can discriminate axial asymmetry of optically active binaphthyldiamine derivatives was prepared by the 'molecular imprinting' technique. A light-radical polymerization in the presence of an axially asymmetric compound, (R)-2,2'-bis-methylcarbonylamino-1,1'-binaphthyl (binaphthyldiamine bis-acetamide (BINADA-ac)) as a template molecule with methacrylic acid (MA) as a functional monomer, and ethyleneglycol dimethacrylate (EGDMA) as a crosslinker, at 4 degrees C. The obtained polymer exhibited a superior enantioselectivity to the (R)-enantiomer by HPLC analyses. This plastic receptor should recognize the template molecule with its shape and character of its functional groups. It should be useful in the development of chiral stationary phases for the optical resolutions of axially asymmetric compounds.


A new view of developmental research for psychoanalysts.
Three major epistemological perspectives in psychoanalysis are summarized, and the developmental research relevant to each is described. Not all research is useful for all psychoanalytic perspectives. The most historically recent of the three perspectives, exemplified by Winnicott, others in the British Independent Group, and the "relationists" in the United States, who focus on the experiential immediacy of the analyst-analysand interaction and emotions, presents new problems and challenges for meaningful dialogue with the developmental researcher. Research in extrapsychoanalytic disciplines has traditionally been posed as authoritative for the grounding of psychoanalytic "truth," and, unlike the earlier perspectives, this view explicity rejects any truth deriving from authority outside the psychoanalytic process itself. To illustrate how developmental research inquiry would be different for each epistemological perspective in psychoanalysis, the same study of infant development is described in three different ways as relevant to each perspective. Child development research has been changing as a field in ways parallel to psychoanalysis, each undergoing fundamental changes that encourage a new integration.


Splanchnic first pass disappearance of threonine and lysine do not differ in healthy men in the fed state.
We previously showed that the splanchnic bed of neonates takes up a significantly higher amount (43%) of threonine in contrast to lysine (12%). We questioned whether this same pattern applied in adult humans and found no information in the literature. Therefore, our objective in the current study was to determine the difference in splanchnic first pass disappearance of threonine and lysine in adult humans during the fed state. During two 5-d study periods, 6 healthy men received l-[1-(13)C]threonine or l-[1-(13)C]lysine enterally or parenterally randomized to either study d 3 or 5, respectively. The diets were in the form of an amino acid mixture providing a protein intake of 1 g · kg(-1) · d(-1) and an energy intake of 1.5 times the resting energy expenditure. Blood and breath samples were collected at baseline and plateau for amino acid and 11CO(2) enrichment. Splanchnic disappearances in adult males were similar for threonine and lysine. The splanchnic disappearance of threonine as a percentage of intake was 17.9% (8.4 mg · kg(-1) · d(-1)) in the healthy men compared with 18.5% (11.2 mg · kg(-1) · d(-1)) for lysine. We conclude that the threonine requirement of the gut of healthy men consuming a liquid formula diet based on free amino acids is similar to the lysine requirement, which is in contrast to our previous findings for neonates.


Cardiovascular and other competing causes of death among patients with cancer from 2006 to 2015: An Australian population-based study.
With improved cancer survivorship, cardiovascular disease (CVD) and other noncancer events compete with cancer as the underlying cause of death, but the risks of mortality in competing-risk settings have not been well characterized. The authors identified 21,637 individuals who had a first cancer registered between 2006 and 2013, with follow-up to 2015, in the Australian population-based Tasmanian Cancer Registry. The cumulative incidence of deaths from specific competing events was assessed in competing-risk analyses. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) for deaths from noncancer causes were calculated for comparison with the general population. Overall, 8844 deaths were observed, with 1946 (22%) from competing events. The cumulative incidence of deaths from CVD increased significantly with age at first cancer diagnosis and exceeded other competing events at age ≥65 years. The risk of death from CVD was more common than expected in the first year of follow-up (SMR, 1.44 [95% confidence interval, 1.26-1.64]; AER, 36.8 per 10,000 person-years). The SMR and AER for CVD deaths varied by first cancer site, indicating increased risks after a first diagnosis of lung cancer, hematologic malignancy, and urinary tract cancer. For other noncancer events, the SMRs increased significantly for deaths from infectious disease and respiratory disease and were highest in the first year of follow-up. CVD was the leading cause of competing mortality among Tasmanian patients with cancer who were diagnosed from 2006 to 2013. The higher than expected occurrence of death from CVD and other noncancer events during the first year after a cancer diagnosis highlights the importance of early preventive interventions.


Anisotropic metal-insulator transition in epitaxial thin films.
By comparing the properties of In and Pb quantum wells in a scanning tunneling microscopy subsurface imaging experiment, we found the existence of lateral bound states, a 2D Mott-Hubbard correlation gap, induced by transverse confinement. Its formation is attributed to spin or charge overscreening of quasi-2D excitations. The signature of the 2D confinement-deconfinement transition is also experimentally observed, with the correlation gap being pinned in the middle of the conduction band. A self-organized 2D Anderson lattice is suggested as a new ground state.


Surgical Fracture Repair in Chronic Renal Failure Patients on Hemodialysis An Analysis of Complications and Hospital Quality Measures.
In end stage renal disease (ESRD) patients on hemodialysis (HD), it is known that renal bone disease has a negative impact on postoperative complication rate of fracture repair compared to non-ESRD patients. Previous studies have examined complications following surgical hip fracture repair in ESRD patients on HD. However, there is paucity of information outside of hip fracture repair. This study was undertaken to investigate complications associated with surgical fracture repair in ESRD patients on hemodialysis and to compare quality measures with a control group for various fracture types. Data of all consecutive ESRD patients on HD was collected prospectively starting in 2013. Charts of 2,558 ESRD patients on HD from 2010 to 2013 were also reviewed. Thirty-four patients who underwent surgical fracture repair were included in the study. Additionally, 1,000 patients without ESRD who underwent fracture repair were also identified, and a random sample of 267 patients was selected for inclusion as a control group. Primary outcomes were major complications as defined by the Clavien-Dindo complication rating system for orthopaedic surgery. Secondary outcomes were minor complications, defined by the same method. Demographic information and hospital quality measures, such as hospital length of stay (LOS) and discharge disposition, were also collected. There were no differences between the two groups in terms of BMI, ethnicity, or gender distribution. The ESRD patients were older than control patients (62.6 versus 46.8 years; p > 0.01). Overall, the complication rate in the ESRD group was 14.7% compared to 3% in the control group (p < 0.05) while the rate of major complications was similar (5.8% versus 2.2%, p = 0.2). The rate of minor complications was higher in the ESRD group though this did not reach statistical significance (8.8% versus 1%, p = 0.07). Median LOS was significantly higher in the ESRD group (15.9 versus 6.4 days; p < 0.01), and patients in the ESRD group were less likely to be discharged to home (29.4% versus 78%; p < 0.01). Surgical fracture repair in ESRD patients can be performed with similar major complication rate as a control group. However, the higher rate of minor complications and poorer hospital quality measures in the ESRD group must be taken into account as we move toward "pay for performance" and bundled payment initiatives for orthopaedic trauma patients.


Statins as the Controlling Agents for Non-Hodgkin's Lymphomas via Increasing the Casein Kinase 2 Interacting Protein-1: A Hypothesis.
Non-Hodgkin's lymphomas (NHL), derived from B- or T-cell, consist of a heterogeneous group of malignant lymphoproliferative disorders. Knockdown of Casein kinase 2 interacting protein-1 (CKIP-1) in NHL promoted cell proliferation and inhibited apoptosis via enhancing phosphorylated Protein Kinase B (PKB or AKT) expression. Statins are the class of drugs that inhibit the ratelimiting step of the mevalonate pathway, which is essential for the biosynthesis of various compounds, including cholesterol. Also, statins have anticancer properties being mediated by different mechanisms. A search on databases like Scopus and PubMed with keywords such as statin and non- Hodgkin's lymphomas was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to evaluate and reconfirm the involved cellular signaling pathway. CKIP-1 is involved in the regulation of cell proliferation and apoptosis while plays an important role in many cancers. We can hypothesize that statins may increase the expression levels of CKIP-1 which could contribute to the reductions in phospho-AKT level. Hence, they may ameliorate the NHL patients via suppressing AKT phosphorylation and increasing CKIP- expression. Present review confirms the positive effect of statins on NHL by increasing CKIP-1 and reducing cell proliferation, subsequently.


DFT study on the selectivity of complexation of metal cations with a dioxadithia crown ether ligand.
The interactions of a dioxadithia crown ether ligand with Li(+), Na(+), K(+), Mg(2+), Ca(2+), and Zn(2+) cations were investigated using density functional theory (DFT) modeling. The modeling was undertaken to gain insight into the mechanism of the selective complexation of the mono- and dications observed with this ligand experimentally. Two types of conformationally different complexes were located with both mono- and dications. In the first conformer, the cation is bonded to the ether oxygens; in the second conformer, the cation is bonded to the alkoxy and suger oxygens. In general, the complexes formed with dications were found to be more stable than those with monocations, with the stability decreasing with the period number within a given periodic table group of elements. The highest stability was observed for the complexes formed with zinc. The complex formed with lithium was the most stable among those involving monovalent cations. The system interaction energy was decomposed into electrostatic (ES), polarization (P), charge-transfer (CT), exchange (EX), and geometry-deformation (DEF) contributions using the self-consistent charge and configuration method for subsystems (SCCCMS). The stabilizing energy components (ES, P, and CT) exhibit the same trend as the total interaction energy, whereas the destabilizing contributions (EX and DEF) exhibit the opposite trend. It was found that the main contributions responsible for stabilization of the dicationic systems are the P and ES energies; in the monocationic systems, the CT stabilization is equally important. The gas-phase preferences changed when the solvent effect was included. The dioxadithia crown ether ligand preserved its selectivity toward Zn(2+), but the selectivity sequence toward monovalent cations was reversed.


[Studies on Pd base ternary alloys for dental amalgam. (Part 2) On the corrosion resistivity (author's transl)].
In the previous paper, the author reported the effect of composition of Pd base ternary alloys on the dimensional change, the compressive strength, hardness and microanalysis by EPMA. In this paper, corrosion resistivity of Pd base ternary alloy amalgam was studied by comparison of reflective light intensity, surface roughness and weight change before and after corosion test in 0.1% Na2S, 0.1% lactive acid and 1% NaCl solution. The main results obtained are as follows: (1) Pd base ternary alloy amalgam showed much higher corrosion resistivity than that of on the market silver-tin-copper amalgam. (2) On the (60 Pd-40 Ag)-Sn alloy amalgam, corrosion resistivity was gradually improved by addition of Sn up to 10 wt% Sn, and the best corrosion resistivity was observed in (60 Pd-40 Ag)-10 Sn among Pd base alloy amalgam tested in this study. (3) On the (60 Pd-40 Ag)-Cu alloy amalgam, corrosion resistivity decreased gradually with increment of Cu content. (4) Weight of (60 Pd-40 Ag)-Sn alloy amalgam was a little increased after corrosion test in 0.1% Na2S solution, but that of (60 Pd-40 Ag)-Cu alloy amalgam showed a tendancy to decrease. (5) Corrosion of Pd base alloy amalgam was observed mainly in the matrix. Tarnish on the core was observed a little. Since fine cut amalgam has the smaller rate of area of core than that of spherical amalgam, surface roughness was comparatively large.


A microwell array-based approach for studying single nanoparticle catalysis with high turnover frequency.
Measuring the catalytical activities of single catalysts in the case of high turnover frequency (TOF, realistic conditions) is highly desirable to accurately evaluate the functional heterogeneities among individuals and to understand the catalytic mechanism. Herein, we report a microwell array-based method to in operando measure the photocatalytic kinetics of single CdS nanoparticles (NPs) with high TOF. This was realized by sealing individual CdS NPs into separated micrometer-sized polydimethylsiloxane wells, thus eliminating the diffusion of products among individuals in the case of high concentration of reactants. This method allowed us to monitor the activities of single catalysts with an average TOF up to 2.1 × 105 s-1. Interestingly, two types of catalytical behaviors were revealed during single CdS photocatalysis: a rapid decline in activity for most CdS NPs and an initial increase in activity followed by a decrease for a minor population of individuals. The developed method will facilitate the investigation of catalytic activities of single particles under realistic conditions and hold great potential in the fields of photo/electro-catalysts, enzymes, functional bacteria, and so on.


[Problems presented by the genetics of atopic dermatitis].
The role of heredity in atopic dermatitis has been known since the 19th century. However, the method of transmission has not been clarified. Studies in twins have been the most interesting and show a greater risk of monozygotes. The work shows a relationship between HLA and atopic dermatitis. Atopic dermatitis is truly a multifactorial illness, the development of which depends not only on one, but several genetic systems, which may be independent or perhaps acting together, and also on environmental factors of which the influence is predominant.


Optical Coherence Tomography and Management of a Retinal Granuloma in Presumed Ocular Sarcoidosis.
Purpose: To highlight the utility of EDI-OCT and periocular steroid administration for the treatment of a retinal granuloma due to presumed ocular sarcoidosis. Methods: Retrospective case-study of a single patient. Results: A 45-year-old African-American male with blurred vision in the right eye was found to have a macula-involving retinal granuloma. Laboratory, imaging, and clinical findings were consistent with a diagnosis of presumed ocular sarcoidosis. Optical coherence tomography (OCT) and fundus photographs were used to document granuloma evolution. Oral prednisone 60mg was initiated and tapered to 10mg within 2 months. Due to systemic side-effects and inadequate treatment response with prednisone, 5 sub-Tenon's triamcinolone acetonide (PSTA) injections were then administered over 7 months, and oral prednisone was discontinued at 6 months. Conclusion: This case demonstrated marked granuloma regression occurring with improvement in visual acuity, highlighting the utility of OCT and PSTA in managing retinal sarcoid granulomas.


Ibrutinib impairs IGF-1-dependent activation of intracellular Ca handling in isolated mouse ventricular myocytes.
The Bruton tyrosine kinase (BTK) inhibitor Ibrutinib is associated with a higher incidence of cardiotoxic side effects including heart failure (HF). Ibrutinib is capable of inhibiting PI3K/Akt signaling in neonatal rat ventricular cardiomyocytes when stimulated with insulin-like growth factor 1 (IGF-1). We therefore hypothesized that Ibrutinib might disrupt IGF-1-mediated activation of intracellular Ca handling in adult mouse cardiomyocytes by inhibiting PI3K/Akt signaling. Isolated ventricular myocytes (C57BL6/J) were exposed to IGF-1 at 10 nmol/L in the presence or absence of Ibrutinib (1 µmol/L) or Acalabrutinib (10 µmol/L; cell culture for 24 ± 2 h). Intracellular Ca handling was measured by epifluorescence (Fura-2 AM) and confocal microscopy (Fluo-4 AM). Ruptured-patch whole-cell voltage-clamp was used to measure ICa. Levels of key cardiac Ca handling proteins were investigated by immunoblots. IGF-1 significantly increased Ca transient amplitudes by ∼83% as compared to vehicle treated control cells. This was associated with unaffected diastolic Ca, enhanced SR Ca loading and increased ICa. Co-treatment with Ibrutinib attenuated both the IGF-1-mediated increase in SR Ca content and in ICa. IGF-1 treated cardiomyocytes had significantly increased levels of pS473Akt/Akt and SERCA2a expression as compared to cells concomitantly treated with IGF-1 and Ibrutinib. SR Ca release (as assessed by Ca spark frequency) was unaffected by either treatment. In order to test for potential off-target effects, second generation BTK inhibitor Acalabrutinib with greater BTK selectivity and lower cardiovascular toxicity was tested for IGF1-mediated activation of intracellular Ca handling. Acalabrutinib induced similar effects on Ca handling in IGF-1 treated cultured myocytes as Ibrutinib in regard to decreased Ca transient amplitude and slowed Ca transient decay, hence implying a functional class effect of BTK inhibitors in cardiac myocytes. Inhibition of BTK by Ibrutinib impairs IGF-1-dependent activation of intracellular Ca handling in adult ventricular mouse myocytes in the face of disrupted Akt signaling and absent SERCA2a upregulation.


The effective management of biochemical recurrence in patients with prostate cancer.
Prostate-specific antigen (PSA) testing has become the primary method of monitoring patients following definitive therapy for clinically localized prostate cancer. After surgery, an immediate detectable rise in PSA is correlated with subsequent local recurrence and/or metastasis. Following radiation therapy, biochemical failure is defined as 3 consecutive rises in PSA above the nadir. Treatment of postoperative or postradiation PSA recurrence involves several modalities, including luteinizing hormone-releasing hormone agonists. Although studies have demonstrated the advantages of early hormone therapy, they have not addressed at what PSA level treatment should begin. A better understanding of PSA's kinetics will lead to a sense of when to begin treatment and when watchful waiting is the more appropriate course.


Transition-metal-catalyzed Suzuki-Miyaura cross-coupling reactions: a remarkable advance from palladium to nickel catalysts.
In the transition-metal-catalyzed cross-coupling reactions, the use of the first row transition metals as catalysts is much more appealing than the precious metals owing to the apparent advantages such as cheapness and earth abundance. Within the last two decades, particularly the last five years, explosive interests have been focused on the nickel-catalyzed Suzuki-Miyaura reactions. This has greatly advanced the chemistry of transition-metal-catalyzed cross-coupling reactions. Most notably, a broad range of aryl electrophiles such as phenols, aryl ethers, esters, carbonates, carbamates, sulfamates, phosphates, phosphoramides, phosphonium salts, and fluorides, as well as various alkyl electrophiles, which are conventionally challenging, by applying palladium catalysts can now be coupled efficiently with boron reagents in the presence of nickel catalysts. In this review, we would like to summarize the progress in this reaction.


Safety and efficacy of second-generation drug-eluting stents compared with bare-metal stents: An updated meta-analysis and regression of 9 randomized clinical trials.
The efficacy of second-generation drug-eluting stents (DES; eg, everolimus and zotarolimus) compared with bare-metal stents (BMS) in patients undergoing percutaneous coronary intervention was challenged recently by new evidence from large clinical trials. Thus, we aimed to conduct an updated systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the efficacy and safety of second-generation DES compared with BMS. Electronic databases were systematically searched for all RCTs comparing second-generation DES with BMS and reporting clinical outcomes. The primary efficacy outcome was major adverse cardiac events (MACE); the primary safety outcome was definite stent thrombosis. The DerSimonian and Laird method was used for estimation of summary risk ratios (RR). A total of 9 trials involving 17 682 patients were included in the final analysis. Compared with BMS, second-generation DES were associated with decreased incidence of MACE (RR: 0.78, 95% confidence interval [CI]: 0.69-0.88), driven by the decreased incidence of myocardial infarction (MI) (RR: 0.67, 95% CI: 0.48-0.95), target-lesion revascularization (RR: 0.47, 95% CI: 0.42-0.53), definite stent thrombosis (RR: 0.57, 95% CI: 0.41-0.78), and definite/probable stent thrombosis (RR: 0.54, 95% CI: 0.38-0.80). The incidence of all-cause mortality was similar between groups (RR: 0.94, 95% CI: 0.79-1.10). Meta-regression showed lower incidences of MI with DES implantation in elderly and diabetic patients (P = 0.026 and P < 0.0001, respectively). Compared with BMS, second-generation DES appear to be associated with a lower incidence of MACE, mainly driven by lower rates of target-lesion revascularization, MI, and stent thrombosis. However, all-cause mortality appears similar between groups.


An unusual case of bilateral maxillary and mandibular para premolar: a case report.
The presence of supernumerary teeth is not uncommon in the general population. They occur more frequently in patients with a family history of such teeth. It is rare to find multiple supernumeraries in individuals with no other associated disease or syndrome. There have been very few documented cases of bilateral maxillary and mandibular supernumeraries in the premolar region. An unusual case of a 35-year-old man with six para premolars and complete dentition is presented.


In vitro propagation of "jarilla" (Larrea divaricata CAV.) and secondary metabolite production.
An efficient protocol for the in vitro germination and propagation of Larrea divaricata CAV. (Jarilla) was established. To determine the effect of different growth regulators on the growth rates and phenol production, apical-node microshoots from in vitro germinated plantlets were incubated on the following media: 1) full-strength MS (Murashige and Skoog) salt medium with different ratios of alpha-naphthaleneacetic acid (NAA) and N(6)-benzyladenine (BA); 2) after pre-treatment with indolebutyric acid (IBA), transfer to MS medium of different inorganic salt strengths; and 3) full-strength MS salt medium with different ratios of sucrose and IBA. Successful microshoot rooting percentages were achieved by the second and third strategies, the highest being 87.5-100%. The maximum principal shoot length and node number obtained by the second strategy corresponded to the plantlets previously induced with 50 microM IBA, and grown on half- or full-strength MS salt media (7.03+/-0.93 and 9.86+/-1.07 cm, respectively) while in the third strategy the most efficient micropropagation medium was full-strength MS salt medium supplemented with 7.5 microM IBA: 3% (w/v) sucrose (7.05+/-1.08 and 7.0+/-1.51 cm, respectively). The phenol concentration was determined by analytical HPLC. The highest content of nordihydroguiaretic acid (NDGA) accumulated in microplants of L. divaricata cultivated on half-strength MS salt medium (35.90+/-3.82 mg/g DW). Reducing the MS medium salt concentration by half, in the absence of IBA, it resulted in a higher NDGA production. NDGA production was not sensitive to the variation of IBA concentration. The medium supplemented with 5% (w/v) sucrose and 2.5 microM IBA induced not only a higher NDGA production but also a higher quercetin production.


Assessing the integrity of the cognitive processes involved in belief reasoning by means of two nonverbal tasks: Rationale, normative data collection and illustration with brain-damaged patients.
Every day, we engage in social interactions with other people which require understanding their as well as our own mental states. Such capacity is commonly referred to as Theory of Mind (ToM). Disturbances of ToM are often reported in diverse pathologies which affect brain functioning and lead to problems in social interactions. Identifying ToM deficits is thus crucial to guide the clinicians in the establishment of adequate rehabilitation strategies for patients. Previous studies have demonstrated that ToM is not a unitary function yet currently there are very few standardized tests which allow identifying the type of cognitive processes affected when a patient exhibits a ToM deficit. In the current study, we present two belief reasoning tasks which have been used in previous research to disentangle two types of processes involved in belief reasoning: self-perspective inhibition and the spontaneous inference of another person's belief. A three-step procedure was developed to provide clinicians with the tools to interpret the patients' performances on the tasks. First, these tasks were standardized and normative data was collected on a sample of 124 healthy participants aged between 18 and 74. Data collected showed a decrease in performance as a function of age only in the task that loaded most in spontaneous other-perspective demands. There was however no effect of gender or educational level. Cut-off scores to identify deficits were then calculated for the different age groups separately. Secondly, the three-step procedure was applied to 21 brain-damaged patients and showed a large diversity of profiles, including selective deficits of the two targeted ToM processes. The diversity of profiles shows the importance to take into account the multiple facets of ToM during the diagnosis and rehabilitation of patients with suspected ToM deficits.


Properties of purified ribonuclease P from Escherichia coli.
The purified protein moiety of ribonuclease P (EC 126.96.36.199) from Escherichia coli, a single polypeptide of molecular weight approximately 17 500, has not catalytic activity by itself on several RNA substrates. However, when it is marked in vitro with an RNA species called M1 RNA, RNase P activity is reconstituted. The rate at which the purified RNase P cleaves any particular tRNA precursor molecule depends on the identity of that tRNA precursor.


Craniopharyngiomas: an update.
Craniopharyngiomas have been challenging practitioners for over 100 years. These benign cystic tumors are thought to be a part of a continuum of ectodermal cystic lesions found in the suprasellar region. They are rare tumors found in both the adult and pediatric populations. Patients most often present with findings associated with ventricular outflow obstruction causing hydrocephalus, optic chiasm compression resulting in visual dysfunction or hypothalamic/pituitary compression leading to endocrinopathy. The mainstay of treatment involves a combination of radical or limited surgery followed by radiotherapy. Other adjunctive strategies include cyst fenestration, Ommaya catheter implantation and brachytherapy. Patients in general have high long-term survival but can have significant tumor- and treatment-associated morbidity requiring a lifetime of medical and psychological management.


Against the stream: Antidepressants are not antidepressants - an alternative approach to drug action and implications for the use of antidepressants.
Although antidepressants are regarded as effective and specific treatments, they are barely superior to placebo in randomised trials, and differences are unlikely to be clinically relevant. The conventional disease-centred understanding of drug action regards antidepressants as targeting an underlying brain process, but an alternative 'drug-centred' view suggests they are psychoactive substances that modify normal mental states and behaviour. These alterations, such as numbing of emotions, may reduce feelings of depression, and also create amplified placebo effects in randomised trials. Patients should be informed that there is no evidence that antidepressants work by correcting a chemical imbalance, that antidepressants have mind-altering effects, and that evidence suggests they produce no noticeable benefit compared with placebo. Declaration of interest The author is co-chairperson of the Critical Psychiatry Network.


Trigger Finger or De Quervain Tenosynovitis after Surgical Treatment for Carpal Tunnel Syndrome.
Objective To evaluate the open surgical treatment for carpal tunnel syndrome as a risk factor for the development of stenosing tenosynovitis that results in trigger finger and De Quervain disease. Materials and Methods A retrospective study analyzing the medical records of patients submitted to open surgical release of carpal tunnel syndrome between 2010 and 2021 in a secondary- and tertiary-level hospital. The following data were collected: pathological history, duration of the follow-up after the surgical treatment for carpal tunnel syndrome, development of trigger finger or De Quervain tenosynovitis, affected fingers, and the interval between the end of surgery and symptom onset. Results We evaluated 802 patients of both genders and with a mean age of 50.1 (±12.6) years. The mean follow-up was of 13 (±16.4) months. The mean time until the development of trigger finger was of 61.4 months, and of 73.7 months for De Quervain disease. The incidence of development of De Quervain disease was of 4.12%, and for trigger finger it was of 10.2%. The most affected digits were the thumb (47.6%), the middle (24.4%), and the ring finger (8.54%). Age was the only factor that showed an association with the risk of developing trigger finger, with an increase of 2% for each increase in age of 1 year. Conclusion The incidence rates for the development of De Quervain disease (4.12%) and trigger finger (10.2%) after the surgical treatment for carpal tunnel syndrome were like those described in the literature. Only age was a factor that influenced the development of trigger finger.


Rupture of a degenerated uterine fibroid as a cause of acute abdomen: a case report.
Uterine fibroid is one of the most common pelvic neoplasms. It is rare for this condition to manifest as acute symptoms necessitating emergency surgical intervention. A 46-year-old, Japanese woman was referred to our emergency room for sudden epigastric discomfort. A pelvic mass was felt, and computed tomography demonstrated a 13-cm hypodense multilocular cystic mass adjacent to the uterus. The anterior wall of the cyst was thinned and discontinued, suggesting rupture of the cyst. There was also massive ascites. Peritoneal irritation caused by rupture of an ovarian cyst was suspected, and an emergency exploratory laparotomy was performed. The patient was found to have a distended cystic mass protruding from the posterior surface of the uterus with 3,200 mL of blood-stained ascites. Closer examination revealed a 1-cm tear on the tumor surface, and both solid and cystic parts to the mass. Microscopically the tumor showed a proliferation of myometrial cells without atypia and hyaline degeneration. These findings were interpreted as a rupture of uterine fibroid after cystic degeneration. Rupture of degenerated cystic fibroid is rare, but it should be included in the differential diagnosis when encountering patients with a cystic tumor and massive ascites.


Neuroinflammation Associated With Inborn Errors of Immunity.
The advent of high-throughput sequencing has facilitated genotype-phenotype correlations in congenital diseases. This has provided molecular diagnosis and benefited patient management but has also revealed substantial phenotypic heterogeneity. Although distinct neuroinflammatory diseases are scarce among the several thousands of established congenital diseases, elements of neuroinflammation are increasingly recognized in a substantial proportion of inborn errors of immunity, where it may even dominate the clinical picture at initial presentation. Although each disease entity is rare, they collectively can constitute a significant proportion of neuropediatric patients in tertiary care and may occasionally also explain adult neurology patients. We focus this review on the signs and symptoms of neuroinflammation that have been reported in association with established pathogenic variants in immune genes and suggest the following subdivision based on proposed underlying mechanisms: autoinflammatory disorders, tolerance defects, and immunodeficiency disorders. The large group of autoinflammatory disorders is further subdivided into IL-1β-mediated disorders, NF-κB dysregulation, type I interferonopathies, and hemophagocytic syndromes. We delineate emerging pathogenic themes underlying neuroinflammation in monogenic diseases and describe the breadth of the clinical spectrum to support decisions to screen for a genetic diagnosis and encourage further research on a neglected phenomenon.


Trabucco versus Rutkow versus Lichtenstein techniques in the treatment of groin hernia. A controlled randomized clinical trial.
The aim of this prospective study is to compare the results of the 3 most common tension-free techniques usually performed (Trabucco vs Rutkow vs Lichtenstein). From January 1993 to December 1995 we selected 150 patients to undergo elective surgery for primary monolateral inguinal hernia. The patients were randomized into 3 groups: in group A (53 patients) we used the original plug and patch technique proposed by Rutkow and Robbins; in group B (47 patients) we introduced a modification to the technique originally described by Trabucco, anchoring the plug to the internal ring, fixing the patch on the pubic tubercle and on the tails of the mesh; in group C (50 patients) the Lichtenstein technique was employed. The study was performed using a randomized single blind controlled trial (RCT). The statistical analysis of our data was performed by c2 test and confirmed by the Fisher exact test. The mean follow-up was 73 months (range:58-94). We had no statistically significant differences in the results of the 3 groups. Otherwise the patients of group C showed a significantly higher incidence of suprapubic or more rare inguino-scrotal haematoma (p<0.0033 C vs B; p <0.0038 C vs A). The mean recovery time was between 12 and 14 days in the 3 groups, with no significant statistical differences. The only difference observed is a higher incidence of postoperative haematoma in group C.


Alveolar damage in AIDS-related Pneumocystis carinii pneumonia.
Pneumocystis carinii pneumonia is the most common and serious of the pulmonary complications of AIDS. Despite this, many basic aspects in the pathogenesis of HIV-associated P carinii pneumonia are unknown. We therefore undertook a light and electron microscopic study of transbronchial biopsy specimens to compare pathologic features of P carinii pneumonia and other HIV-related lung diseases. Thirty-seven consecutive HIV-infected patients undergoing a diagnostic bronchoscopy. P carinii pneumonia was characterized by an increase in inflammation, edema, exudate, fibrosts, type II pneumocyte proliferation, and cellular infiltration of the alveolar wall when compared with other lung diseases (all p < 0.05). Electron microscopy showed apposition of the trophozoite to the type I pneumocyte. Erosion of type I pneumocytes was observed in 13 of 15 patients with P carinii pneumonia, whereas none without P carinii pneumonia had this finding (p < 0.05). Erosion of the type II pneumocyte was not observed. Inflammation, interstitial fibrosis, and alveolar epithelial erosion are characteristic features of P carinii pneumonia. The changes may form the pathologic basis for the respiratory failure seen in patients with P carinii pneumonia. Electron microscopy did not show any diagnostie advantage over conventional light microscopy using routine stains.


CyberKnife Radiosurgery - Value as an Adjunct to Surgical Treatment of HCC?
CyberKnife radiosurgery (CK) is an effective tool for the treatment of malignancies. Its greatest potential is in high-dose radiosurgery delivered to targets in organs that move with respiration, e.g., liver tumors. For hepatocellular carcinoma (HCC), however, surgical treatment (resection, transplantation) is most likely to produce long-term survival; for non-resectable tumors, therapies other than radiosurgery are typically recommended. This study evaluated the long-lasting anti-tumor effects of CK combined with surgery in patients with HCC. MATERIALS AND METHODS : Eighteen patients (three women, 15 men) were included in this prospective observational study. They received 21 single-fraction CK treatments (26 Gy). Patient characteristics, treatment effects, tumor response (according to the Response Evaluation Criteria In Solid Tumors (RECIST) grading) and survival were measured for a median period of 29 months. Local tumor control was achieved in 15 patients, with complete and partial remission observed in 10 and five patients, respectively. One patient was treated for two separate lesions in one session, and one received three treatments each separated by two-year intervals; both patients are tumor-free. Two patients showed minimal response, and in one patient local tumor viability could not be excluded by MRI. Nine patients had HCC recurrence, all distant to the treated site. Nine patients died during follow-up, including two with clear relation to tumor progress. Tumor-free survival was 79.4% after one year and 29.8% after three years, and the corresponding overall survival was 84.8% and 66%. CONCLUSION : This study shows the high effectiveness of single-session frameless CyberKnife radiosurgery for treatment of hepatocellular carcinoma and reconfirms previous results of fractioned radiotherapy of HCC. It also demonstrates the potential of radiosurgery to be combined with surgical concepts.


Assessing shared respiratory pathogens between domestic (Ovis aries) and bighorn (Ovis canadensis) sheep; methods for multiplex PCR, amplicon sequencing, and bioinformatics to characterize respiratory flora.
Respiratory disease is responsible for dramatic population declines in bighorn sheep (Ovis canadensis), and respiratory pathogen diagnostics contribute to the management of bighorn populations. To create a comprehensive and consistent approach to bighorn sheep respiratory diagnostics, we created a culture-independent assay to detect and strain type Mannheimia haemolytica, Bibersteinia trehalosi, Pasteurella multocida, and Mycoplasma ovipneumoniae. The assay also detects and characterizes the Pasteurellaceae leukotoxin A gene, and broadly assesses the bacterial composition of each sample based on 16S rRNA sequences. The assay is based on a three-step approach: 1) Multiplex PCR to amplify targets including eight loci for each bacterial species, the Pasteurellaceae lktA gene, and the 16S rRNA gene 2) Library preparation, barcoding, and short-read Illumina sequencing to determine the genetic sequences of each target, and 3) Bioinformatics in the form of automated software to analyze genetic sequences. The assay was designed to assess shared pathogens between domestic and bighorn sheep, but could be useful for many applications in bighorn sheep respiratory disease research and management.


Factors associated with medication adherence among adults with asthma.
Asthma medication adherence is of crucial importance for successful disease management. The aim of this study was to identify and rank factors associated with medication adherence among adults with asthma in the general population. We used data on physician-diagnosed asthma, medication adherence, and factors associated with asthma medication adherence from the Danish General Suburban Population Study using a cross-sectional study design. We ranked factors associated with asthma medication adherence based on the magnitude of odds ratios, and the population attributable fractions. Among 20,032 individuals from the general population, 1,128 (6%) suffered from asthma and 822 (73%) of these were adherent to asthma medications. Based on odds ratios, the three top-ranked factors associated with asthma medication adherence were asthma attacks within the past year (4.0; 95% CI: 2.9-5.5), allergy medication use (3.8; 2.6-5.6), and age above median (3.4; 2.4-4.7), followed by asthma severity markers like airway obstruction, and coughing with mucus. Based on population attributable fractions, the three top-ranked factors associated with adherence to asthma medications were asthma attacks within the past year (70%), age above median (57%), and use of allergy medication (49%). The study showed that in the general population recent asthma attacks, higher age, and taking allergy medication were the three most important factors associated with asthma medication adherence. The importance of maintaining adherence to asthma medications even in the absence of severe disease or expressed asthma symptoms should be better communicated to the general population.


The chimeric cyclic nucleotide-gated ion channel ATCNGC11/12 constitutively induces programmed cell death in a Ca2+ dependent manner.
The hypersensitive response (HR) involves programmed cell death (PCD) in response to pathogen infection. To investigate the pathogen resistance signaling pathway, we previously identified the Arabidopsis mutant cpr22, which displays constitutive activation of multiple defense responses including HR like cell death. The cpr22 mutation has been identified as a 3 kb deletion that fuses two cyclic nucleotide-gated ion channel (CNGC)-encoding genes, ATCNGC11 and ATCNGC12, to generate a novel chimeric gene, ATCNGC11/12. In this study, we conducted a characterization of cell death induced by transient expression of ATCNGC11/12 in Nicotiana benthamiana. Electron microscopic analysis of this cell death showed similar characteristics to PCD, such as plasma membrane shrinkage and vesicle formation. The hallmark of animal PCD, fragmentation of nuclear DNA, was also observed in ATCNGC11/12-induced cell death. The development of cell death was significantly suppressed by caspase-1 inhibitors, suggesting the involvement of caspases in this process. Recently, vacuolar processing enzyme (VPE) was isolated as the first plant caspase-like protein, which is involved in HR development. In VPE-silenced plants development of cell death induced by ATCNGC11/12 was much slower and weaker compared to control plants, suggesting the involvement of VPE as a caspase in ATCNGC11/12-induced cell death. Complementation analysis using a Ca2+ uptake deficient yeast mutant demonstrated that the ATCNGC11/12 channel is permeable to Ca2+. Additionally, calcium channel blockers such as GdCl3 inhibited ATCNGC11/12-induced HR formation, whereas potassium channel blockers did not. Taken together, these results indicate that the cell death that develops in the cpr22 mutant is indeed PCD and that the chimeric channel, ATCNGC11/12, is at the point of, or up-stream of the calcium signal necessary for the development of HR.


Intensity-modulated and image-guided radiotherapy in patients with locally advanced inoperable pancreatic cancer after preradiation chemotherapy.
Radiotherapy (RT) in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC), even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) may improve effectiveness and reduce radiotherapy-related toxicities. Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT), modalities of radiotherapy, and toxicities. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. 15 (68%) women and 7 men (median age 64 years; range 40-77) were identified. Median duration of PRCT was 11.1 months (range 4.3-33.0). Six patients (27%) underwent conventional RT and 16 patients (73%) advanced IMRT and IGRT; median dosage was 50.4 (range 9-54) Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT) was 5.8 months, 2.6 months in the conventional RT group (conv-RT), and 7.1 months in the IMRT/IGRT group (P = 0.029); median OS was 11.0 months, 4.2 months (conv-RT), and 14.0 months (IMRT/IGRT); P = 0.141. Median RT-specific PFS for patients with prolonged PRCT > 9 months was 8.5 months compared to 5.6 months for PRCT < 9 months (P = 0.293). This effect was translated into a significantly better median RT-specific overall survival of patients in the PRCT > 9 months group, with 19.0 months compared to 8.5 months in the PRCT < 9 months group (P = 0.049). IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy.


[Efficacy of lidocaine on seizures by intravenous and intravenous-drip infusion].
We retrospectively studied the efficacy of intravenous and intravenous-drip infusion administration of lidocaine on seizures treated in Saitama Children's Medical Center during the period of 1997-2002. Thirty eight seizures of 29 children (12 boys and 17 girls, average age 41.4 months) were treated with lidocaine. The overall rate of effectiveness was 53%. The response to lidocaine appeared within 5 minutes in all episodes. Good response to lidocaine was noted, in 36% of patients with epilepsy, in 72% with CNS infection and in 80% with benign infantile convulsions; in 42% with generalized seizures and in 63% with partial seizures. Thus there was no significant difference in efficacy among the underlying disorders and seizure types. The adverse reaction of SpO2 decrease was found in one patient. We conclude that lidocaine can be used as a second-line, anti-convulsive drug in status epilepticus based on its prompt effectiveness and low risk of side effects.


Nonextensive kinetics of fluorescence resonance energy transfer.
Some fluorescence dyes in complex media, such as those found in biology, demonstrate nonextensive kinetics, which implies representing their fluorescence decays in terms of lifetime distributions rather than simple exponentials. Complex kinetics usually discourage application to lifetime sensors, as it is believed, that additional molecular mechanisms employed for detection of an analyte will make the resulting kinetics ambiguous and the sensor response inconclusive. In this paper we investigate theoretically the applicability of complex dye kinetics as a fluorescence resonance energy transfer based lifetime sensor and demonstrate that the nonextensive nature of its kinetics does not decrease the sensing performance, and indeed even provides richer structural information than a simple exponential behavior.


Bcl10 plays a critical role in NF-kappaB activation induced by G protein-coupled receptors.
G protein-coupled receptors (GPCRs) play pivotal roles in cell proliferation, differentiation, and survival. Although many studies indicate that the stimulation of GPCRs leads to NF-kappaB activation, the molecular mechanism by which GPCRs induced NF-kappaB activation remains largely unknown. Bcl10 is an essential adaptor molecule connecting antigen receptor signaling cascades to NF-kappaB activation in lymphocytes. However, the function of Bcl10 in nonlymphoid cells remains to be determined. In this study, we demonstrated that the deficiency of Bcl10 resulted in the defect in NF-kappaB activation induced by either expressing the constitutively active mutant of G protein or stimulation of cells with lysophosphatidic acid or endothelin-1, which activate their GPCR. In contrast, TNF-alpha-, LPS-, and integrin-induced NF-kappaB activation was not affected in Bcl10-deficient cells. Together, our results provide genetic evidence showing that Bcl10 is a key signaling component mediating NF-kappaB activation induced by GPCRs in nonlymphoid cells.


Reproductive and toxic effects of methanol extract of Alchornea cordifolia leaf in male rats.
Alchornea cordifolia leaf is traditionally used for the treatment of venereal diseases and for the enhancement of fertility throughout its area of distribution in Africa. The effect of oral administration of the methanol extract of the leaf was evaluated on some reproductive and haematological parameters of male rats at 0 (control group), 100, 200, 400, 800 and 1600 mg kg(-1) . The toxicity study revealed nonsignificant alterations (P > 0.05) in the values of total and differential white blood cell count, but the erythrocyte count, packed cell volume, haemoglobin concentration and haematometric indices were significantly decreased (P < 0.05) at 1600 mg kg(-1) dose. Markers of hepatic damage (aspartate aminotransferase and alanine aminotransferase) and renal damage (urea and creatinine) were significantly elevated (P < 0.05) at 800 and 1600 mg kg(-1) . The bioactivity (reproductive) study revealed significant increases (P < 0.05) in testicular weight, sperm count and motility, and serum testosterone levels, at the 200 and 400 mg kg(-1) . The study concludes that the extract of Alchornea cordifolia leaves has toxic potential at 800 mg kg(-1) and 1600 mg kg(-1) doses, but is safe and has beneficial effects on male reproduction when used at doses equal to or lower than 400 mg kg(-1) .


[Evidence-based proposals for improving the Zemsky Doctor program].
Currently, more and more attention is paid to the shortage of medical staff in rural and remote areas. In order to ensure the staffing of medical institutions with workers in rural areas, in the regions one-time compensations are paid as part of an event called "Zemsky Doctor". However, "Zemsky Doctor" has shown a fading effect over the years of implementation, including due to the unwillingness of medical students to participate in this program. The purpose of the work is to identify the attitude of students of medical universities to participation in the "Zemsky Doctor" program and develop measures to increase the attractiveness of the program. To achieve the goal of the study, we conducted a survey of 250 medical students from all over Russia, interviews with medical students, with medical staff, including former and current participants. The novelty of the work lies in the study of the attitude of current and potential participants in the program in order to develop proposals for its improvement. To improve the program, it is necessary to choose the term for concluding the contract, differentiate payments depending on the distance from the regional center, create an information site, defer the army for the duration of the contract.


Test-retest reliability of the Welfare Quality Assessment protocol for pigs applied to sows and piglets. Part 2. Assessment of the principles good feeding, good housing, and good health1.
The present study aimed at testing the feasibility and on-farm test-retest reliability of the Welfare Quality Assessment protocol for pigs applied to sows and piglets. The study was conducted on 13 farms in Northern Germany, which were visited 5 times by the same observer, and included 2 experimental setups: first, the complete Welfare Quality Assessment protocol for sows and piglets was applied to the farms. Second, additional assessments in the gestation unit considered all sows. The complete protocol assessments were used to evaluate the feasibility of the protocol. Furthermore, the data were analyzed with regard to on-farm test-retest reliability. The present publication focuses on the Welfare Quality principles good feeding, good housing, and good health, which are based on individual indicators (IN). The second experimental setup was utilized to verify the test-retest reliability of IN in the gestation unit with an increased number of animals under assessment. The test-retest reliability was calculated using Spearman's rank correlation coefficient (RS), intraclass correlation coefficient (ICC), smallest detectable change (SDC), and limits of agreement (LoA). Farm visit 1 (F1; day 0) was set as a reference and compared with farm visits 2 to 5 (F2 to 5; day 3, week 7, month 5, month 10). The IN of the above-named Welfare Quality principles achieved mostly acceptable test-retest reliability (e.g., wounds on the body F1 to F4: RS 0.34 to 0.57, ICC 0.40 to 0.41, SDC 0.02 to 0.12, LoA [-0.03; 0.02] to [-0.09; 0.14]) in terms of the on-farm test-retest reliability. Poor test-retest reliability was detected for body condition score concerning the principle good feeding, for bursitis and panting in sows and for huddling and panting in piglets within the principle good housing, and finally for vulva lesions, metritis, and local infections in sows and for scouring and lameness in piglets in the principle good health. Variations among the farm visits, which resulted in poor test-retest reliability, may be explained by seasonal effects (panting), moving animals (bursitis, lameness, huddling), rare occurrences of diseases (metritis, local infections, scouring), and differently conditioned sow groups (body condition score). The second experimental setup confirmed the results for IN in the gestation unit. Thus, the reported test-retest reliability determines the Welfare Quality Assessment protocol for sows and piglets to be a reliable approach to assess welfare in sows and piglets.


Effect of polymer, poly(ethylene glycol)(PEG-400), on solvent and rotational relaxation of coumarin-480 in an ionic liquid containing microemulsions.
The effect of a polymer, polyethylene glycol with a molecular weight of 400 (PEG-400), on the dynamics of solvent and rotational relaxation have been investigated in [bmim][BF4]/TX100/cyclohexane microemulsions using steady state and time resolved fluorescence spectroscopy as a tool and coumarin 480 (C-480) as a fluorescence probe. The size of the microemulsions increases with addition of PEG-400, which was revealed by dynamic light scattering (DLS) measurement. This leads to faster collective motion of the cations and anions of [bmim][BF4], which contributes to faster solvent relaxation in microemulsions.


Delayed diagnosis of dermal leiomyosarcoma mimicking keloid scar.
A 43-year-old man developed an abnormal scar 6 months following excision of a leiomyoma from his left shoulder. The scar was elevated, irregular in shape, pink-red in colour, hard in consistency and it was extending beyond the margins of the original wound. A diagnosis of a keloid scar was considered and the patient was managed as such. He underwent a planned procedure for intralesional excision of the keloid scar. The histopathological examination showed a diagnosis of leiomyosarcoma. This case report presents a delayed diagnosis of dermal leiomyosarcoma mimicking a keloid scar. The patient subsequently underwent wider excision of the tumour with curative intention.


Recent advances in the activation of boron and silicon reagents for stereocontrolled allylation reactions.
Despite the popularity of boron and silicon allylation reagents in stereocontrolled synthesis, they suffer from a number of inherent limitations that have slowed down their development as synthetic tools for nucleophilic additions to carbonyl compounds and imine derivatives. These limitations are the low reactivity and diastereoselectivity of allyl trialkylsilane reagents, and the lack of catalytic systems for the activation and substoichiometric control of enantioselectivity in the additions of allyl boron reagents. To develop more efficient and general methods for the control of absolute stereochemistry in the resulting homoallylic alcohols, new approaches aimed at solving the problem of activation of allylic boron and silicon reagents are needed. This Minireview describes a number of recent approaches that have been devised to address this problem.


Analysis of foot strike pattern, rearfoot dynamic and foot rotation over childhood. A cross-sectional study.
The purpose of this study was to determine the foot strike patterns (FSP), rearfoot position at initial contact (RPic, i.e., No INV/EVE) and foot rotation in children in relation to age. A total of 932 children aged 3 to 16 years participated in this study. A sagittal and frontal-plane video was recorded using a high-speed camcorder to analyse these variables. There is a significant increase (p < 0.001) of rearfoot strike patterns (RFS) prevalence in relation to age; e.g. preschool children (3-6 years old) displayed an RFS prevalence 46.65% and the adolescent population(15-16 years old) an RFS prevalence 92.20%. The total RFS prevalence in all samples was 69.25%. There was a significant reduction (p < 0.001) of prevalence of RPic in relation to age groups; preschool children displayed a prevalence of RPic 60.37% and the adolescent population 10%. There was a significant reduction (p < 0.001) of prevalence of no foot rotation in relation to age groups; preschool children displayed a prevalence of no foot rotation 48.95% and the adolescent population 13.55%. In conclusion, FSP in children are influenced by age. It is noteworthy that the RFS prevalence of children is lower in comparison to the adult population.


The comparison of preemptive analgesic effects of curcumin and diclofenac.
Preemptive analgesia is an antinociceptive treatment that prevents central sensitization. Antinociceptive effects of diclofenac are well-known. The aim of this study was to investigate preemptive analgesic effects of curcumin and diclofenac, before acute and inflammatory induced pain in rat model. Fourty eight old female (n = 6 in each group) Wistar Albino rats were included in the study. Paw movements in response to paw flinching in response to formalin injection or thermal stimulation were compared after curcumin (400 mg kg-(1), p.o.) and diclofenac (10 mg kg(-1), i.p.) administration. Saline was used as a control. The solvent ethanol was administered in another group of rats. Preemptive analgesic effect was significant in both tests when curcumin and diclofenac was administrated before the pain stimuli. Oral administration of curcumin and intraperitoneal injection of diclofenac increase the response time in hot plate test and decrease the number of flinches in formalin test (p < 0.001 vs p < 0.05). These results suggest that curcumin had preemptive analgesic effects on acute thermal, and inflammatory induced pain in rats as diclofenac (Fig. 2, Ref. 35).


Mechanically stapled esophagojejunostomy. Results of a prospective series of 176 cases.
To evaluate the reliability of stapled esophagojejunostomy. We studied a non-selected prospective series of 176 consecutive total gastrectomies (169 cancers, 7 benign pathologies). Hand-sewn esophagojejunostomy was performed 5 times after failure of the stapled esophagojejunostomy. There were fourteen hospital deaths (8%), and 63 patients (36%) presented complications. There were 5 anastomotic leaks (2.8%) but non were responsible for deaths. In these 5 cases, there had been an incident during construction of the esophagojejunostomy. Such an incident was the only significant risk factor for an anastomotic leak: 17% after an incident and 0% in the absence of an incident (p < 0.001). We observed no cases of anastomotic stricture. Stapled esophagojejunostomy is a reliable technique when technical precautions are taken. It is easier to reproduce than hand-sewn esophagojejunostomy and has demonstrated low specific morbidity and no direct mortality.


Acylated flavonol glycosides from Tagetes minuta with antibacterial activity.
Wild marigold (Tagetes minuta), a flowering plant of the family Asteraceae contains compounds of pharmaceutical and nutritional importance especially essential oils and flavonols. Identification, characterization of flavonols and determination of their antibacterial activity were major objectives of the current study. The isolation and purification of flavonols was accomplished using chromatographic techniques while structural elucidation was completed by LC-MS and NMR spectroscopy. The extracts and purified compounds were tested against various bacterial strains for antibacterial activity. A total of 19 flavonols were isolated from this species. Of these, 17 were of butanol and two of ethyl acetate extracts. Based on the concentration and purity, eight potential flavonols were selected and structurally elucidated. Four flavonols, 6-hydroxyquercetin 7-O-β-(6''-galloylglucopyranoside; 2), 6-hydroxykaempferol 7-O-β-glucopyranoside (5), 6-hydroxykaempferol 7-O-β-(6''-galloylglucopyranoside; 7), 6-hydroxyquercetin 7-O-β-(6''-caffeoylglucopyranoside; 9), were identified for the first time from T. minuta. Butanol and ethyl acetate extracts of flowers and seeds showed significant antibacterial activity against Micrococcus leteus, Staphylococcus aureus, Bacillus subtilis, and Pseudomonas pikettii. Among the isolated flavonols only 1, 2, and 18 were found to possess significant antibacterial activity against M. luteus. The extracts and purified flavonols from T. minuta can be potential candidates for antibacterial drug discovery and support to ethnopharmacological use.


The Psychology of Resistance to Change: The Antidotal Effect of Organizational Justice, Support and Leader-Member Exchange.
In today's business environment, the survival and sustenance of any organization depend upon its ability to introduce a successful change. However, in implementing a change, one of the biggest problems an organization faces is resistance from its employees. The current paper addresses this problem by examining the role of organizational justice dimensions in coping with the resistance to change through the intervening role of perceived organizational support (POS), leader-member exchange (LMX), and readiness for change (RFC) in a sequential framework. Data of 372 employees have been collected from the banking industry of Pakistan. The results obtained through the Partial Least Squares- Structural Equation Modeling (PLS-SEM) approach using SmartPLS suggest that distributive justice, procedural justice, and interactional justice play a critical role in lowering the resistance to change through POS, LMX, and RFC, contributing significantly to the theory and practice. Furthermore, this study also discusses recommendations for future research and limitations associated with this research work.


Human Brucellosis: Risks and Prevalence among Iranian Blood Donors Residing in Endemic Areas.
Brucellosis is a common zoonotic infection worldwide. Transmission can be occasionally observed via transfusion or transplantation. This study was designed to survey the seroprevalence of anti-Brucella antibody in blood donors in different endemic provinces. A total of 14,706 blood donors from the 5 most prevalent provinces were studied by standard tube agglutination (STA) and any positive subjects were further confirmed by 2-mercaptoethanol agglutination test (2-ME). Significant titres were 80 for STA and 40 for 2-ME. A total of 63 (0.43%) serum samples were STA-positive. Of these, the 2-ME test was reactive in 42 samples. The 2-ME test was reactive in 31 samples with a low titre. However, concomitant STA ≥80 and the titre of ≥40 for the 2-ME test were found in 11 subjects (0.075%), mostly resident in urban areas. Exposure to manure products was identified as a significant risk factor (p = 0.0128). Conclusion : The observed data show a somewhat noticeable prevalence among Iranian blood donors, bringing attention to the importance of pre-donation screening via a questionnaire which supplies answers about occupational history, and any history of exposure or past infections. Further studies to evaluate the frequency and related risk factors in certain populations, in conjunction with implementing stricter regulations in blood donor selection in endemic areas, may be necessary.


On-line optimization of biotechnological processes: I. Application to open algal pond.
A new on-line optimization and control procedure applicable to biotechnological systems for which a precise mathematical model is unavailable has been developed and tested. The proposed approach is based on an online search for optimum operating conditions by an automatic system using a modified simplex algorithm to which several features have been added to permit real time operation. The simplex algorithm is the upper level of a hierarchical software package in which the other levels are cost evaluation, control, data acquisition, and signal processing. The optimization method was tested in a laboratory minipond for the cultivation of Spirulina platensis. The controlled parameters were light intensity, optical density, pH, and temperature. The proposed optimization method can be applied to other biological processes provided that the pertinent variables can be measured and controlled and the cost function can be defined mathematically.


Tannin is a key factor in the determination and prediction of energy content in sorghum grains fed to growing pigs.
This study was conducted to determine and compare the DE and ME content as well as the apparent total tract digestibility (ATTD) of GE in 28 samples of sorghum grain fed to growing pigs and to generate prediction equations for DE, ME, and the ATTD of GE based on chemical analysis. The 28 samples included 8 low-tannin sorghum cultivars (LTS; tannin ≤ 0.16%), 10 medium-tannin sorghum cultivars (MTS: 0.67% ≤ tannin ≤ 0.98%), and 10 high-tannin sorghum cultivars (HTS; 1.11% ≤ tannin ≤ 1.51%) obtained from 9 provinces in China and 3 samples of LTS cultivars were obtained internationally. The 28 diets were formulated to contain 96.9% of 1 of the 28 sorghum grains and 3.1% of vitamins and minerals. Eighty-four barrows (36.5 ± 3.4 kg initial BW) were used in a randomized complete block design conducted during 2 consecutive periods ( = 6 per treatment) with the pigs fed different diets during the 2 periods. For each period, pigs were placed in metabolic crates for a 5-d total collection of feces and urine following 7 d of adaptation to the diets. Among the 28 samples, GE, CP, and ADF content (DM basis) ranged from 4,363 to 4,496 kcal/kg, 8.26 to 13.41%, and 3.26 to 5.78%, respectively. The average tannin content was 0.08, 0.84, and 1.29% in the LTS, MTS, and HTS samples, respectively. The DE and ME content (DM basis) ranged from 3,861 to 3,989 and from 3,784 to 3,905 kcal/kg, respectively, in LTS; from 3,646 to 3,740 and from 3,588 to 3,669 kcal/kg, respectively, in MTS; and from 3,481 to 3,617 and from 3,418 to 3,538 kcal/kg, respectively, in HTS. The mean DE, ME, DE/GE, ME/GE, and ATTD of GE in MTS were less than those in LTS ( < 0.05) and greater than those in HTS ( < 0.05). The correlation coefficients between DE, ME, or the ATTD of GE and tannin content were all -0.96 ( < 0.01). The best-fit equations for DE and ME (kcal/kg DM) for the complete set of 28 sorghum grains were 6,974 - (236 × % tannin) - (43.27 × % ADF) + (24.96 × % CP) - (0.71 × % GE) for DE and 3,973 - (262 × % tannin) - (27.24 × % ADF) for ME. Our results strongly indicate that the DE and ME content of sorghum grains are related to their chemical composition, especially their tannin content. The DE and ME content could decrease by more than 200 kcal/kg when the tannin content is increased by 1% in the sorghum grain. Overall, tannin is a key predictor for the DE and ME content as well as the ATTD of GE in sorghum grains, and the potent antinutritive properties from tannin should not be ignored when sorghum is used as an energy source for pigs.


Addressing racial and ethnic barriers to effective health care: the need for better data.
Racial and ethnic disparities in health outcomes and quality of care have been observed among persons with similar health insurance, within the same system of care, and within the same health plan. National efforts to eliminate these disparities are hindered by the lack of race/ethnicity data. Collection of these data by health care providers, coupled with standards for collection, use, and privacy protection, would be a first step toward eliminating disparities. Although no national consensus exists with respect to data collection, the weight of prior research, related public and private efforts, and growing diversity of the U.S. population are likely to increase demand for accurate data on race and ethnicity in health care settings.


Whole-body imaging of a hypercholesterolemic female zebrafish by using synchrotron X-ray micro-CT.
Zebrafish has been used as a powerful model system in biological and biomedical studies studying development and diseases. Comparative, functional, and developmental studies on zebrafish morphology require precise visualization of 3D morphological structures. Few methods that can visualize whole-volume of zebrafish tissues are available because optical bio-imaging methods are limited by pigmentation and hard tissues. To overcome these limitations, the 3D microstructures of a hypercholesterolemic zebrafish model are visualized using synchrotron X-ray micro-computed tomography (SR-μCT). The model spatial resolution ranged from sub- to several microns. The microstructures of various zebrafish organs are observed by combining high-contrast staining (osmium tetroxide and uranyl acetate) and embedding a protocol to enhance the image contrast of soft tissues. Furthermore, blood vessels are identified using a barium sulfate injection technique. The internal organs and cells, such as liver, intestine, oocytes, and adipocytes, of a hypercholesterolemic zebrafish are compared with those of normal organs and cells. The SR-μCT is useful for understanding the pathogenesis of circulatory vascular diseases by detecting the modifications in the 3D morphological structures of the whole body of the zebrafish. This bio-imaging technique can be readily used to study other disease models.


Feasibility of Using the Mosquito Blood Meal for Rapid and Efficient Human and Animal Virus Surveillance and Discovery.
Mosquito blood meals taken from humans and animals potentially represent a useful source of blood for the detection of blood-borne pathogens. In this feasibility study, Anopheles stephensi mosquitoes were fed with blood meals spiked with dengue virus type 2 (DENV-2) and harvested at serial time points. These mosquitoes are not competent vectors, and the virus is not expected to replicate. Ingested blood was spotted on Whatman FTA cards and stored at room temperature. Mosquito abdomens were removed and stored at -80°C. Control blood meal aliquots were stored in vials or applied onto FTA cards. After 4 weeks of storage, the samples were extracted using beadbeating and QIAamp Viral RNA kit (Qiagen Sciences, Germantown, MD). Recovered viral RNA was analyzed by DENV-2 TaqMan RT-PCR assay and next-generation sequencing (NGS). Overall viral RNA recovery efficiency was 15% from the directly applied dried blood spots and approximately 20% or higher for dried blood spots made by blotting mosquito midgut on FTA cards. Viral RNA in mosquito-ingested blood decreases over time, but remains detectable 24 hours after blood feeding. The viral sequences in FTA-stored specimens can be maintained at room temperature. The strategy has the potential utility in expedited zoonotic virus discovery and blood-borne pathogen surveillance.


Increased Frequency of Mesorectal and Perirectal LN Involvement in T4 Prostate Cancers.
Patients with prostate cancer presenting with advanced T stage, mainly T4, might have a unique pattern of nodal failure and disease involvement that is not typically covered when local therapy is offered. We attempted to identify common sites of nodal disease presentation and failure for patients presenting with cT4 prostate cancer. All patients with treatment-naïve cT4 prostate cancer were retrospectively identified. All patients were required to have a confirmed diagnosis reviewed by our genitourinary pathologist and completed baseline staging. Lymph node (LN) involvement and location at diagnosis were reviewed by a genitourinary radiologist. All patients' follow-up scans were also reviewed; based on LN size, imaging characteristics, and progression/regression characteristics on systemic therapy, the locations of sites of LN failure were recorded. For patients who underwent surgery, any pathologically involved LNs and their anatomic locations were recorded. A total of 103 patients met these criteria, with a median follow-up of 8 years (range, 0.5-14 years). Rectal involvement by the primary disease was associated with a higher risk of perirectal and mesorectal LN involvement (45%) relative to no rectal involvement (26%) (P < .05). These echelons are typically not covered with conventional pelvic external beam radiation therapy and are not routinely part of pelvic LN dissection in patients treated surgically. Conversely, bladder or pelvic side wall invasion did not correlate with increased frequency of involvement of perirectal/mesorectal LNs (P > .05). When offering local therapy, target modification to include the perirectal and mesorectal LNs should be considered for patients presenting with T4 prostate cancer with rectal involvement.


Curcumin analog, GO-Y078, induces HO-1 transactivation-mediated apoptotic cell death of oral cancer cells by triggering MAPK pathways and AP-1 DNA-binding activity.
GO-Y078, a new synthetic analogue of curcumin (CUR), has higher oral bioavailability and anticancer activity than CUR, but the oncostatic effect of GO-Y078 on oral squamous cell carcinoma (OSCC) is largely unknown. In the present study, we examined the oncostatic properties and possible mechanisms of GO-Y078 on human SCC-9 and HSC-3 OSCC cells. Our results indicated that GO-Y078 showed a cytostatic effect against OSCC cells, and this antiproliferative phenomenon stemmed from a mechanism involving multiple levels of cooperation, including cell-cycle G2/M arrest and apoptosis induction. Mechanistically, GO-Y078 treatment induced caspase-mediated apoptosis via upregulating two apoptosis-modulating proteins, SMAC/DIABLO and heme oxygenase (HO)-1. GO-Y078 transcriptionally induced upregulation of the HO-1 gene by increasing the AP-1 DNA-binding activity, which was initiated by activation of the p38 /JNK1/2 pathways. In the clinic, patients with head and neck cancers expressed lower HO-1 and SMAC/DIABLO levels in primary cancer tissues compared to normal tissues. Clinical datasets also revealed that patients with head and neck cancers expressing high HO-1 had afavorable prognosis. Our results provide new insights into the role of GO-Y078-induced molecular regulation in suppressing OSCC growth and suggest that GO-Y078 has potential therapeutic applications for OSCC.


Ophthalmic findings in 10 captive, anesthetized chimpanzees (Pan troglodytes).
To document ophthalmic findings, Schirmer's tear test I (STT), and intraocular pressure (IOP) values for anesthetized chimpanzees (Pan troglodytes). Ten captive chimpanzees from Zoo Knoxville and Chattanooga Zoo. Ten chimpanzees were anesthetized for annual physical examinations, blood collection, and ophthalmic examination. Each was anesthetized with intramuscular (IM) injections of dexmedetomidine, midazolam, and ketamine. Ophthalmic findings and STT and IOP values in addition to general health information were recorded for each chimpanzee. Pupillary diameter was measured after topical tropicamide administration. A Shapiro-Wilk test of normality was done for age, weight, STT values, IOP values, and pupil size. Ages ranged from 11 to 42 years. Weight range was 40.9-83.6 kg. The mean STT was 13.4 ± 5.3 mm/min. The mean IOP was 14 ± 4.2 mm Hg. Seven of the 10 chimpanzees were considered geriatric, and each had perilimbal lipid deposits. Sedative-associated miosis was successfully counteracted with a regimen of repeated applications of tropicamide, enabling complete fundic examination. A complete ophthalmic examination can be done on anesthetized chimpanzees with the protocol used in this study.


MNET++: Music-Driven Pluralistic Dancing Toward Multiple Dance Genre Synthesis.
Numerous task-specific variants of autoregressive networks have been developed for dance generation. Nonetheless, a severe limitation remains in that all existing algorithms can return repeated patterns for a given initial pose, which may be inferior. We examine and analyze several key challenges of previous works, and propose variations in both model architecture (namely MNET++) and training methods to address these. In particular, we devise the beat synchronizer and dance synthesizer. First, generated dance should be locally and globally consistent with given music beats, circumvent repetitive patterns, and look realistic. To achieve this, the beat synchronizer implicitly catches the rhythm enabling it to stay in sync with the music as it dances. Then, the dance synthesizer infers the dance motions in a seamless patch-by-patch manner conditioned by music. Second, to generate diverse dance lines, adversarial learning is performed by leveraging the transformer architecture. Furthermore, MNET++ learns a dance genre-aware latent representation that is scalable for multiple domains to provide fine-grained user control according to the dance genre. Compared with the state-of-the-art methods, our method synthesizes plausible and diverse outputs according to multiple dance genres as well as generates remarkable dance sequences qualitatively and quantitatively.


Graphene-coated double D-type low loss optical fiber modulator.
A graphene-coated double D-type low loss all-fiber modulator is proposed. The modulator is improved on the basis of standard fiber. Only the cladding is processed without grinding the original core structure. The upper and lower cladding are cut same distance. This can ensure that the mode field does not deviate in one direction, so that most of the mode field is still tied to the core, which greatly reduces the device loss. The existence of the double graphene layer can also ensure a very excellent modulation efficiency. The calculation results show that the mode loss of our proposed dual-D modulator under X polarization is 0.125 dB/mm, and the mode field mismatch loss is 0.25%. The mode loss in Y polarization is 0.033 dB/mm, and the mode field mismatch loss is 0.32%. When the modulation voltage is 5 V, the modulation depth is 78.4% under the condition of five-layer graphene, while the modulation speed can reach 15.38 GHz. Besides maintaining low modulation voltage and higher modulation efficiency, this structure makes full use of the advantages of good fiber coupling, and will be widely used in future fiber communications and all-fiber systems.


Microsecond photocapacitance transients observed using a charged microcantilever as a gated mechanical integrator.
How light is converted to electricity in blends of organic donor and acceptor molecules is an unsettled question, partly because the spatial heterogeneity present in these blends makes them challenging to characterize. Although scanned-probe measurements have provided crucially important microscopic insights into charge generation and transport in these blends, achieving the subnanosecond time resolution needed to directly observe the fate of photogenerated charges has proven difficult. We use a charged microcantilever as a gated mechanical integrator to record photocapacitance indirectly by measuring the accumulated change in cantilever phase as a function of the time delay between precisely synchronized voltage and light pulses. In contrast with previous time-resolved scanned-probe photocapacitance measurements, the time resolution of this method is set by the rise and fall time of the voltage and light pulses and not by the inverse detection bandwidth. We demonstrate in an organic donor-acceptor blend the ability of this indirect, "phase-kick" technique to record multiexponential photocapacitance transients on time scales ranging from 40 μs to 10 ms. The technique's ability to measure subcycle, nanosecond charge dynamics is demonstrated by measuring the tens of nanosecond sample electrical charging time.


Development of a rapid point-of-care patient reported outcome measure for cataract surgery in India.
For patient undergoing cataract surgery in India, existing patient-reported outcome (PRO) measures are either not culturally relevant, have not been adequately validated, or are too long to be used in a busy clinical setting. We sought to develop and validate a brief and culturally relevant point-of-care PRO measure to address this need. Twelve items from the Indian Visual Functioning Questionnaire (IND-VFQ) were selected based on preliminary data. Patients 18 years and older were prospectively recruited at Aravind Eye Care System in Madurai, India. Clinical and sociodemographic data were collected and the 12-item short-form IND-VFQ (SF-IND-VFQ) was administered pre- and post-operatively to 225 patients; Factor analysis and Rasch modeling was performed to assess its psychometric properties. One item that did not fit a unidimensional scale and had poor fit with the Rasch model was eliminated from the questionnaire. The remaining 11 items represented a single construct (no residual correlations> 0.1) and were largely unaffected by differential item functioning. Five items had disordered thresholds resolved by collapsing the response scale from four to three categories. The survey had adequate reliability (0.80) and good construct (infit range, 0.77-1.29; outfit range, 0.56-1.30) and content (item separation index, 5.87 logits) validity. Measurement precision was fair (person separation index, 1.97). There was evidence that items were not optimally targeted to patients' visual ability (preoperatively, - 1.92 logits; overall, - 3.41 logits), though the survey measured a very large effect (Cohen's d 1.80). In a subset of patients, the average time to complete the questionnaire was 2 min 6.3 s. The SF-IND-VFQ is a valid, reliable, sensitive, and rapidly administered point-of-care PRO measure to assess changes in visual functioning in patients undergoing cataract surgery in India.


Adoptive immunotherapy for hematological malignancies using T cells gene-modified to express tumor antigen-specific receptors.
Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI) and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL) for melanoma. Currently, along with advances in synthetic immunology, gene-modified T cells retargeted to defined tumor antigens have been introduced as "cellular drugs". As the functional properties of the adoptive immune response mediated by T lymphocytes are decisively regulated by their T-cell receptors (TCRs), transfer of genes encoding target antigen-specific receptors should enable polyclonal T cells to be uniformly redirected toward cancer cells. Clinically, anticancer adoptive immunotherapy using genetically engineered T cells has an impressive track record. Notable examples include the dramatic benefit of chimeric antigen receptor (CAR) gene-modified T cells redirected towards CD19 in patients with B-cell malignancy, and the encouraging results obtained with TCR gene-modified T cells redirected towards NY-ESO-1, a cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. This article overviews the current status of this treatment option, and discusses challenging issues that still restrain the full effectiveness of this strategy, especially in the context of hematological malignancy.


5-Azacytidine-induced reactivation of the human X chromosome-linked PGK1 gene is associated with a large region of cytosine demethylation in the 5' CpG island.
Hamster-human cell hybrids containing an inactive human X chromosome were treated with 5-azacytidine and derived clones were examined for phosphoglycerate kinase activity and cytosine methylation in the human PGK1 (X chromosome-linked phosphoglycerate kinase) gene. Comparisons between expressing and nonexpressing clones indicated that demethylation of several methylation-sensitive restriction sites outside of the 5' CpG island were unnecessary for expression. High-resolution polyacrylamide gel analysis of 25 Hpa II, Hha I, and Tha I sites revealed that all clones expressing PGK1 were unmethylated in a large region of the CpG island that includes the transcription start site and 400 base pairs upstream. Many nonexpressing clones had discontinuous patterns of demethylation. Remethylation was often observed in subclones of nonexpressing hybrids. These data suggest that a specific zone of methylation-free DNA within the PGK1 promoter is required for transcription. In addition, the presence of neighboring methylcytosines appears to decrease the heritable stability of unmethylated CpGs in this region.


MyoCell, a cell-based, autologous skeletal myoblast therapy for the treatment of cardiovascular diseases.
Cell therapy is fast emerging as a potential therapeutic option in cardiovascular therapeutics. Because of their inherent myogenic differentiation potential, skeletal myoblasts (SkMs) have been extensively assessed in preclinical and clinical studies for their feasibility, safety and effectiveness for myocardial repair. Bioheart Inc is developing MyoCell, autologous SkMs delivered by MyoCath and MyoStar catheter delivery systems, for the treatment of cardiovascular diseases such as myocardial infarction and congestive heart failure. MyoCell is undergoing phase II/III clinical development and has so far demonstrated safety and efficacy, including improvements in cardiac function in phase I/II clinical trials.


Full correlation analysis of conformational protein dynamics.
Correlated motions in biomolecules are often essential for their function, for example, allosteric signal transduction or mechanical/thermodynamic energy transport. Principal component analysis (PCA) is a widely used method to extract functionally relevant collective motions from a molecular dynamics (MD) trajectory. Being based on the covariance matrix, however, PCA detects only linear correlations. Here we present a new method, full correlation analysis (FCA), which is based on mutual information and thus quantifies all correlations, including nonlinear and higher order correlations. For comparison, we applied both, PCA and FCA, to approximately 100 ns MD trajectories of T4 lysozyme and the hexapeptide neurotensin. For both systems, FCA yielded better resolved conformational substates and aligned its modes more often with actual transition pathways. This improved resolution is shown to be due to a strongly increased anharmonicity of FCA modes as compared to the respective PCA modes. The high anharmonicity further suggests that the motions extracted by FCA are functionally more relevant than those captured by PCA. In summary, FCA should provide improved collective degrees of freedom for dimension-reduced descriptions of macromolecular dynamics.


Value of Chromosome 9p21 Polymorphism for Prediction of Cardiovascular Mortality in Han Chinese Without Coronary Lesions: An Observational Study.
Variants at chromosome 9p21 are associated with coronary artery disease (CAD). However, the longitudinal effects of 9p21 variants on cardiovascular mortality remain controversial and may depend on whether the patient has CAD. We tested the hypothesis that the single-nucleotide polymorphism (SNP) rs4977574 is associated longitudinally with cardiovascular death in patients without detectable coronary lesions. We enrolled patients who underwent coronary angiography for angina pectoris but had normal angiographic findings. Laboratory analyses and rs4977574 TaqMan genotyping were performed using fasting blood samples collected during hospitalization. Cardiovascular and all-cause mortality rates were acquired from a national database. Among the 679 enrolled subjects with neither myocardial infarction nor an angiographic coronary lesion, 28 (19.0%) of the 147 homozygous GG carriers suffered a cardiovascular death, compared with 63 (11.8%) of the 532 subjects with the AG or AA genotype during the median 12.3 years (interquartile range 8.6-12.7 years) of follow-up. In a recessive model, cardiovascular mortality was significantly higher in subjects with the GG genotype than in those with the other genotypes (hazard ratio, 1.69, 95% confidence interval 1.08 to 2.64; P = 0.021). In this follow-up study, rs4977574, a tag SNP at chromosome 9p21, was shown to be associated with cardiovascular mortality in Taiwanese patients with angina pectoris but no coronary lesions.


[Myocardial work in assessment of left ventricular systolic function].
This review focuses on a new method for noninvasive, complex evaluation of left ventricular (LV) systolic function using an echocardiography-based technology of computing indexes of myocardial performance by construction of pressure-deformation curves. Since this new method accounts for the effect of afterload on myocardial contractility, the article presents data demonstrating advantages of the evaluation of LV myocardial performance over the speckle-tracking echocardiography and other methods in diagnostics of several diseases. The review provides a description of this method and its advantages and limitations. The authors analyzed results of major studies on evaluation of LV performance. Prospects of implementation and practical use of the method are discussed in the aspects of diagnostics of cardiovascular diseases and risk stratification for different groups of patients.


Detection of mRNA and immunoreactive proteins for acidic and basic fibroblast growth factor and expression of the fibroblast growth factor receptors in the bovine oviduct.
The heparin-binding acidic and basic fibroblast growth factors (aFGF, bFGF) and their receptors in the bovine oviduct are described. By means of western blot analysis one 18 kDa aFGF and two bFGF proteins (16 and 18 kDa, respectively) were detected in oviductal flushings. Different concentrations of these two growth factors could be measured in oviductal flushings during the oestrous cycle: concentrations of aFGF protein were significantly higher at ovulation (mean +/- SEM; 5.3 +/- 0.5 ng ml-1) than during the luteal phase (3.0 +/- 0.3 ng ml-1); concentrations of bFGF were higher at the preovulatory stage (3.5 +/- 0.7 ng ml-1) than at the post-ovulatory stage (1.3 +/- 0.15 ng ml-1). Immunohistochemical studies using a/bFGF-specific antibodies indicated that these growth factors were localized mainly in oviduct epithelial cells. The sequence of the bovine FGF receptor (FGFR) was partly determined. Quantification of mRNAs by an RNase-protection assay (RPA) showed that expression of aFGF and bFGF was different during the oestrous cycle, indicating that the regulation of aFGF is separate from that of bFGF. Only mRNA encoding bFGF and FGFR could be detected in cumulus-oocyte complexes by reverse transcription PCR. In summary, the components of the FGF system were found in the bovine oviduct suggesting an autocrine or paracrine regulation involving oviduct cells and cumulus-oocyte complexes.


Context matters-the phased development of an adaptable food literacy intervention: Up for Cooking.
Adapting interventions to the context increases the impact and sustainability of interventions. Literature acknowledges the need to adapt existing interventions and that these adaptations should be clearly reported. However, little is known about how to incorporate adaptation from the beginning. This paper argues that interventions should be developed and adaptations should be made using an ongoing non-linear approach. An action-oriented research approach with feedback loops is proposed. We illustrate this with the development of a food literacy intervention 'Up for Cooking' (Dutch: Zin in Koken) and present lessons learned in developing, implementing and studying such adaptable interventions. Interventions should clearly define and differentiate the intervention function and form. Implementers, in turn, should be encouraged to tailor interventions within a form that fits with a specific context. Sufficient time, continuous adaptation based on co-creation, feedback loops and interdisciplinary collaboration are important prerequisites for the development of adaptable interventions.


Thyroid hormone deiodinases during embryonic development of the saltwater crocodile (Crocodylus porosus).
All tissues of the embryonic saltwater crocodile (Crocodylus porosus) gradually increased in weight during development except for lung tissue, which had a peak weight of 1.09 g at day 67, thereafter decreasing in weight. The brain was a relatively large organ. Deiodinase activities in liver, kidney, lung, heart, gut, and brain from day 29 to day 77 of development of the saltwater crocodile were investigated. High-K(m) reverse triiodothyronine (rT(3)) outer ring deiodination (ORD) activity was present in all tissues except the brain. Activity ranged from 559 +/- 51.3 pmol rT(3) deiodinated/mg protein/min in the liver at day 77 to below 10 pmol rT(3) deiodinated/mg protein/min in gut, lung, and heart tissue. rT(3) ORD increased during development in the liver and kidney but decreased in the gut and lung. Activity in the heart was very low (less than 2 pmol rT(3) deiodinated/mg protein/min) and did not change during development. Low-K(m) thyroxine (T(4)) ORD in liver and kidney tissue had peaks of activity around day 49 of incubation (0.52 and 0.09 fmol T(4) deiodinated/mg protein/min, respectively). After day 49, T(4) ORD activity in these tissues decreased. T(4) ORD activity in gut, lung, and heart was very low (less than 0.04 fmol T(4) deiodinated/mg protein/min), with activity in lung increasing slightly during the rest of development. T(4) ORD activity in the brain increased toward day 77 (0.14 +/- 0.03 fmol T(4) deiodinated/mg protein/min), illustrating its importance in local triiodothyronine (T(3)) production during brain development. T(3) inner ring deiodination activity was present only in the embryonic liver and peaked at day 49 (10.1 fmol T(3) deiodinated/mg protein/min), after which activity decreased.


The Galpha12/13 family of heterotrimeric G proteins and the small GTPase RhoA link the Kaposi sarcoma-associated herpes virus G protein-coupled receptor to heme oxygenase-1 expression and tumorigenesis.
Heme oxygenase-1 (HO-1), an inducible enzyme that metabolizes the heme group, is highly expressed in human Kaposi sarcoma lesions. Its expression is up-regulated by the G protein-coupled receptor from the Kaposi sarcoma-associated herpes virus (vGPCR). Although recent evidence shows that HO-1 contributes to vGPCR-induced tumorigenesis and vascular endothelial growth factor (VEGF) expression, the molecular steps that link vGPCR to HO-1 remain unknown. Here we show that vGPCR induces HO-1 expression and transformation through the Galpha(12/13) family of heterotrimeric G proteins and the small GTPase RhoA. Targeted small hairpin RNA knockdown expression of Galpha(12), Galpha(13), or RhoA and inhibition of RhoA activity impair vGPCR-induced transformation and ho-1 promoter activity. Knockdown expression of RhoA also reduces vGPCR-induced VEFG-A secretion and blocks tumor growth in a murine allograft tumor model. NIH-3T3 cells expressing constitutively activated Galpha(13) or RhoA implanted in nude mice develop tumors displaying spindle-shaped cells that express HO-1 and VEGF-A, similarly to vGPCR-derived tumors. RhoAQL-induced tumor growth is reduced 80% by small hairpin RNA-mediated knockdown expression of HO-1 in the implanted cells. Likewise, inhibition of HO-1 activity by chronic administration of the HO-1 inhibitor tin protoporphyrin IX to mice reduces RhoAQL-induced tumor growth by 70%. Our study shows that vGPCR induces HO-1 expression through the Galpha(12/13)/RhoA axes and shows for the first time a potential role for HO-1 as a therapeutic target in tumors where RhoA has oncogenic activity.


[Selective retina therapy: methods, technique, and online dosimetry].
Selective retina therapy (SRT) is currently under evaluation, as a new and very subtle laser method, for the treatment of retinal disorders associated with a degradation of the retinal pigmentary epithelium (RPE). SRT makes it possible to selectively effect the RPE, sparing the adjacent neural retina with the photoreceptors and also the choroid below the RPE. In the best case, the therapy leads to regeneration of the RPE and a long-term metabolic increase at the chorio-retinal junction. In contrast to conventional laser photocoagulation, which is associated with complete thermal necrosis of and around the treated site, absolutely no scotoma occurs in SRT. This paper reviews the methods and mechanisms behind the selective effects of the RPE. In vitro and preclinical results are used to describe the bandwidth of selective effects with respect to different irradiation settings. An optoacoustic technique is introduced to visualize effects that cannot be seen by ophthalmoscopy and to facilitate dosimetry control without recourse to angiography completes the report.