Post-translational modification derived products (PTMDPs): toxins in chronic diseases?
In living organisms, proteins are progressively modified by spontaneous non-enzymatic reactions generating many post-translational modification derived products (PTMDPs) which exert deleterious effects and may be considered endogenous toxins in diabetes mellitus and chronic renal failure. Non-enzymatic glycation, which refers to the spontaneous binding of reducing sugars to free amino groups, is increased in diabetes mellitus because of hyperglycemia and is amplified by oxidative processes ('glycoxidation'). Glycoxidation leads to the formation of 'advanced glycation end products' (AGEs), together with products of other oxidative pathways. AGEs alter tissue organization and cell-protein interactions, mainly in the case of long-lived extracellular matrix proteins, and interact with membrane receptors, among which RAGE (receptor of AGEs), a multiligand receptor which triggers intracellular signaling pathways stimulating inflammatory functions. Another major protein modification, carbamylation, is increased in chronic renal failure, which may occur during the course of diabetes mellitus. Carbamylation is due to the binding of isocyanic acid on the α-NH2 extremity of proteins or amino acids, or on ε-NH2 lysine groups, generating homocitrulline, a potential biomarker in atherosclerosis. Isocyanic acid is formed in vivo either by spontaneous dissociation of urea or by myeloperoxidase action on thiocyanate. Carbamylated proteins exhibit altered properties. For example, carbamylated collagen is unable to stimulate oxidative functions of polymorphonuclear neutrophils but increases matrix metalloproteinase-9 production by monocytes. Lipoprotein functions are altered by carbamylation and may contribute to atherogenesis. Thus, the numerous PTMDPs may be considered both hallmarks of protein damage in chronic diseases and endogenous toxins acting at the molecular and cellular levels.


[The clinical significance of plasma tissue plasminogen activator (t-PA) levels in severe acute or fulminant hepatitis].
We studied the tissue plasminogen activator (t-PA) levels in the plasma of patients with acute hepatitis (AH), severe acute hepatitis (AHs) and fulminant hepatitis (FH). Plasma t-PA levels were measured consecutively on the first, third and seventh days of hospitalization. Plasma t-PA levels were markedly higher in AHs and FH than in AH (p < 0.05, p < 0.01, respectively) on the first day, but did not differ significantly between AHs and FH on this day. The t-PA levels decreased markedly on the third and seventh days in AHs (both p < 0.05), but did not change from the first day to the third and seventh days in FH. The t-PA levels on the third and seventh days were higher in FH than in AHs (both p < 0.05). There was a significant increase in the plasma t-PA level before an episode of encephalopathy in FH compared with levels in AHs. These observations suggest that t-PA level may be useful as a prognostic parameter in patients with acute hepatic injury.


Induction of unstable and stable chromosomal aberrations by 99mTc: in-vitro and in-vivo studies.
Biological dosimetry, which determines the dose of acquired radiation by measuring radiation-induced variation of biological parameters, can help assess radiation damage in an individual. Evaluation of radiation exposure requires setting up reference curves for each type of radiation. To evaluate the potential induction of chromosome aberrations by a clinical diagnostic dose of 99mTc. Dicentrics, rings, excess fragments, complete reciprocal translocations and incomplete reciprocal translocations were scored in peripheral blood lymphocytes from patients exposed to a 99mTc bone scintigraphy. A specific relationship between the radiation dose delivered by 99mTc and the frequency of stable and unstable chromosomal aberrations was established in vitro to estimate whole-body dose. Chromosome analysis using fluorescence plus Giemsa and fluorescence in-situ hybridization was undertaken on six patients before and after a 99mTc bone scintigraphy. Dicentrics, rings, excess fragments, and translocations were scored in blood lymphocytes after in vitro 99mTc external irradiation in order to construct dose calibration curves. Analysis of the in-vitro data shows that the number of both unstable and stable aberrations has a quadratic linear relationship to the dose. Our in-vivo irradiation studies showed that activities of 99mTc-hexamethylene diphosphonate (99mTc-HDP) used for bone investigations do not induce any additional unstable chromosome aberrations and translocations. The frequencies obtained did not differ significantly from background values. 99mTc can produce unstable and stable chromosomal aberrations in vitro. 99mTc-HDP administration does not induce supplementary chromosomal aberrations. The dose-response curves will allow a more accurate evaluation of the risk related to in-vivo administration of 99mTc labelled radiopharmaceuticals, and they can be used to assess the safe upper limit of injected activity in humans.


Draft Genome Sequence of Mn(II)-Oxidizing Pseudomonas resinovorans Strain MO-1.
Pseudomonas resinovorans strain MO-1, which possesses a high ability to oxidize Mn(II), has been isolated from oligotrophic pond sediment. The draft genome sequence consists of 6,252,942 bp and has a G+C content of 63.4%. Strain MO-1 has 5,694 coding sequences, including 13 putative Mn(II) oxidation genes.


S-Adenosylmethionine protects against acetaminophen-induced hepatotoxicity in mice.
An overdose of acetaminophen (APAP) is the most frequent cause of fulminant liver failure in the United States. Increasing evidence demonstrates that oxidative stress plays an important etiologic role in APAP-induced liver injury. S-Adenosylmethionine (SAMe) is a key intermediate in the hepatic trans-sulfuration pathway and serves as a precursor for glutathione (GSH) as well as the methyl donor in most transmethylation reactions. In the present study, we investigated effects of SAMe on liver injury induced by APAP administration in male C57BL/6 mice. Two related studies were performed. In the first experiment, SAMe (1g/kg BW) was injected intraperitoneally 4 h before APAP (600 mg/kg BW) administration. In the second experiment, SAMe was injected intraperitoneally 1 h after APAP administration. Our results showed that APAP administration induced changes typical of confluent centrilobular necrosis by histological examination and a marked elevation in serum alanine aminotransferase (ALT) activity. APAP administration induced significant decreases in both hepatic and blood SAMe concentrations. In addition, APAP decreased intracellular (both cytosolic and mitochondrial) GSH concentrations along with increased lipid peroxidation in conjunction with mitochondrial dysfunction as documented by Ca2+-induced mitochondrial permeability transition. SAMe treatment (both before and after APAP) significantly attenuated the liver injury. Exogenous SAMe prevented the decrease in liver and blood SAMe concentrations. Moreover, SAMe treatment attenuated both cytosolic and mitochondrial GSH depletion as well as mitochondrial dysfunction. We conclude that SAMe at least in part protects the liver from APAP-induced injury by preventing intracellular GSH depletion and mitochondrial dysfunction.


[Breast cancer--diagnosis and treatment in a Alesund hospital].
We wanted to check if our routines for diagnosing and treating primary operable breast cancer and ductal carcinoma in situ were concordant with national guidelines and quality standards. Data were retrospectively collected from medical journals for all relevant patients operated at Alesund Hospital, Norway from 1.11.02 to 1.05.08. 487 breasts were operated in 478 patients. A triple-diagnostic approach (mammography/ultrasound, clinical examination and biopsy) was used in 98 % of patients and ultrasound-guided core-needle-biopsy in 86 %. For 82 % of patients one visit in an out-patient-department was enough to conclude with a malignant diagnosis. A sentinel node biopsy was taken for 378 of 457 (83 %) patients operated in the axilla; a sentinel node was found in 93 % of them. Three (median) sentinel nodes were removed (spread in the range 1 - 12). 51 % of patients had breast-conserving surgery. From diagnosis of cancer to completion of all surgical procedures, 57 patients (12 %) had two operations, three (0.6 %) had three operations (in the breast and axilla), and 89 % of patients had completed all surgery within three weeks.13 % of patients had postoperative complications. After axillary lymph-node dissection, 20 % of patients had lymph-oedema/shoulder/arm pain. Three patients had ipsilateral relapse in the breast or thoracic wall. None had axillary relapse after sentinel-node biopsy. The median observation time was 26 months (0 - 66 months). The results of diagnosis and treatment in our hospital are in good accordance with our national guidelines and quality standards.


Clinical effects and economical impact of dutasteride and finasteride therapy in Italian men with LUTS.
To investigate differences in the risk of benign prostatic hyperplasia (BPH)- related hospitalization, for surgical and non-surgical reasons, and of new prostate cancer (PCa) diagnosis between patients under dutasteride or finasteride treatment. A retrospective cohort study was conducted using data from record-linkage of administrative databases. Men aged ≥ 40 years old who had received a prescription for at least 10 boxes/year (index years: 2004-06) were included. The association of the outcomes was assessed using a multiple Cox proportional hazard model. Propensity score matched analysis and a 5-to-1, greedy 1:1 matching algorithm were performed. The budget impact analysis of dutasteride vs finasteride in BPH-treated patient was performed. From an initial cohort of about 1.5 million of Italian men, 19620 were selected. The overall hospitalization for BPH-non surgical reasons, for BPH-related surgery and for new detection of PCa incidence rates (IRs) were 8.20 (95% CI, 7.62-8.23), 18.0 (95% CI, 17.12-18.93) and 8.62 (95% CI, 8.03-9.26) per 1000 person-years, respectively. The multivariate analysis after the propensity score-matching showed that dutasteride was associated with an independent reduced likelihood of hospitalization for BPH-related surgery (HR 0.82; 95% CI 0.73-0.93; p = 0.0025) and of newly detected PCa (HR: 0.76,95% CI, 0.65-0.85; p = 0.0116). The IR for BPH-non surgical reasons was 8.07 (95% CI, 7.10-9.17) and 9.25 (95% CI, 8.19-10.44) per 1000 person-years, respectively. The IR for BPH-related surgery was 18.28 (95% CI, 17.17-20.32) and 21.28 (95% CI, 19.24-23.06) per 1000 person-years among patients under dutasteride compared with those under finasteride, respectively. For new-onset PCa, the IR was 8.01 (95% CI, 7.07-9.08) and 9.38 (95% CI, 8.32-10.58) per 1000 person-years The pharmacoeconomical evaluation showed that the net budget impact of the use of dutasteride vs. finasteride in 1000 BPH-treated patient for 1 year induces a saving of 3933 €. The clinical effects of dutasteride and finasteride are slightly different. The likelihood of hospitalization for BPH-related surgery and of newly detected PCa seems to be in favor of dutasteride. The budget impact analyses showed a slightly benefit for dutasteride. Comparative prospective studies are necessary to confirm these results.


Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy.
Psychopathy is a personality disorder associated with a profound lack of empathy. Neuroscientists have associated empathy and its interindividual variation with how strongly participants activate brain regions involved in their own actions, emotions and sensations while viewing those of others. Here we compared brain activity of 18 psychopathic offenders with 26 control subjects while viewing video clips of emotional hand interactions and while experiencing similar interactions. Brain regions involved in experiencing these interactions were not spontaneously activated as strongly in the patient group while viewing the video clips. However, this group difference was markedly reduced when we specifically instructed participants to feel with the actors in the videos. Our results suggest that psychopathy is not a simple incapacity for vicarious activations but rather reduced spontaneous vicarious activations co-existing with relatively normal deliberate counterparts.


The relationship between parenting stress and parent-child interaction with health outcomes in the youngest patients with type 1 diabetes (0-7 years).
To test whether parenting stress and the quality of parent-child interaction were associated with glycemic control and quality of life (QoL) in young children (0-7 years) with type 1 diabetes (T1DM), we videotaped 77 families with a young child with T1DM during mealtime (including glucose monitoring and insulin administration). Parent-child interactions were scored with a specifically designed instrument. Questionnaires assessed general and disease-related parenting stress and (diabetes-specific (DS)) QoL. HbA(1c) (glycemic control) was extracted from the medical records. Both general and disease-related parenting stress were associated with a lower (DS)QoL (r ranged from -0.39 to -0.70, p < 0.05), but not with HbA(1c) levels. Furthermore, with regard to the parent-child interaction, emotional involvement of parents (r = 0.23, p < 0.05) and expressed discomfort of the child (r = 0.23, p < 0.05) were related to suboptimal HbA(1c) levels. There was no clear pattern in the correlations between parent-child interaction and (DS)QoL. The results support the notion that diabetes does not only affect the child with T1DM: T1DM is a family disease, as parenting factors (like stress and parent-child interactions) are associated with important child outcomes. Therefore, it is important for health-care providers to not only focus on the child with T1DM, but also on the family system.


Solute carrier transporter and drug-related nephrotoxicity: the impact of proximal tubule cell models for preclinical research.
The final excretion step of several drugs is facilitated by membrane transporters of the Solute carrier (SLC) family expressed in the proximal tubules of the kidney. Membrane transporters contribute substantially to the pharmacokinetic profile of drugs and play important roles in drug-induced nephrotoxicity. Different cell models have been applied as tools for the assessment of nephrotoxic effects caused by drugs. This review gives an overview over clinically relevant SLC transporters involved in the renal elimination of drug agents and their specific role in drug-induced nephrotoxicity. Most widely applied cell models are described and their advantages and limitations are outlined. In vitro cell culture models (e.g., continuous and primary renal cell lines, polarized cell monolayers) represent valuable tools for early assessment of the nephrotoxic potential of drugs. Since SLC transporters contribute to drug excretion in a large part, in vitro cell culture models might be very helpful to study transport pathways and/or potential drug-drug interactions at an early stage of the drug development process to predict nephrotoxic effects.


Large sample bounds on the survivor average causal effect in the presence of a binary covariate with conditionally ignorable treatment assignment.
A common problem when conducting an experiment or observational study for the purpose of causal inference is "censoring by death," in which an event occurring during the experiment causes the desired outcome value - such as quality of life (QOL) - not to be defined for some subjects. One approach to this is to estimate the Survivor Average Causal Effect (SACE), which is the difference in the mean QOL between the treated and control arms, considering only those individuals who would have had well-defined QOL regardless of whether they received the treatment of interest, where the treatment is imposed by the researcher in an experiment or by the subject in the case of an observational study. Zhang and Rubin [5] (Estimation of causal effects via principal stratification when some outcomes are truncated by "death". J Educ Behav Stat 2003;28:353-68) have proposed a methodology to calculate large sample bounds - bounds on the SACE that assume that the exact QOL distribution for each arm is known or that the finite sample size can be ignored - in the case of a randomized experiment. We examine a modification of these bounds in the case where a binary covariate describing each of the subjects is available and assignment to the treatment or control group is ignorable conditional on the covariate. Using a dataset involving an employment training program, we find that the use of the covariate does not substantially change the bounds in this case, although it does weaken the assumptions about the sample and thus make the bounds more widely applicable. However, simulations show that the use of a binary covariate can in some cases dramatically narrow the bounds. Extensions and generalizations to more complicated variants of this situation are discussed, although the amount of computation increases very quickly as the number of covariates and the number of possible values of each covariate increase.


[A case of lethal interstitial pneumonia after neoadjuvant chemotherapy for advanced gastric cancer].
We report a case of lethal interstitial pneumonia that occurred after neoadjuvant chemotherapy for advanced gastric cancer. A 76-year-old man with no history of interstitial pneumonia received 2 courses of S-1 (100 mg/body) following 1 course of S-1 plus cisplatin( CDDP) from June 2012. He complained of dyspnea on exertion 6 days after completion of the treatment. Chest radiography and computed tomography (CT) revealed diffuse interstitial lesions in bilateral lung fields. Bronchoalveolar lavage( BAL) revealed an increased number of lymphocytes and leukocytes. Transbronchial lung biopsy (TBLB) revealed interstitial pneumonia with fibrous thickening in the alveolar septum. The drug lymphocyte stimulation test (DLST) was positive for S-1 and negative for CDDP. These results suggested that S-1 had induced interstitial pneumonia. Steroid therapy( 40 mg/day prednisolone following 500 mg methylprednisolone pulse therapy) and an antibiotic agent were administered but were ineffective. He rapidly developed respiratory failure and required tracheal intubation and mechanical ventilation on hospital day 24, and died on hospital day 38.


Activation of hexose transport by antibody.
In our attempts to study alterations in cell behaviour by membrane perturbations, the effects of specific antisera on membrane functions were examined. The present communication reports the nature and kinetics of the changes in hexose transport as a result of treatment of L6 rat myoblast cells with specific antibodies. Exposure to complement-inactivated rabbit anti-myoblast antiserum resulted in an almost immediate two- to three-fold increase in hexose transport; morphological changes were observed only after prolonged incubation with the antiserum. Similar stimulation of hexose transport was observed upon exposure of cells to immunoglobulin G (IgG) from both sheep anti-myoblast and rabbit anti-myoblast plasma membrane sera. It seems that the interaction of specific IgG with cell surface components is sufficient to elicit this response. We have established that over 90% of 2-deoxyglucose is phosphorylated upon entrance into rat myoblasts and that exposure of cells to specific antibody does not cause changes in cell volume or general leakiness of the cell membrane. The antibody-stimulated hexose transport system resembles its normal counterpart in its substrate affinity and specificity; it differs from that of the control cells only in the transport capacity. This increase in hexose capacity is brought about by processes independent of protein synthesis and is not likely the result of extensive reorganization of membrane components.


A systematic review of predictors and screening instruments to identify older hospitalized patients at risk for functional decline.
To determine a valid, reliable and clinical user-friendly instrument, based on predictors of functional decline, to identify older patients at risk for functional decline. The predictors of functional decline are initially considered and, subsequently, the characteristics and psychometric qualities of existing screening instruments are investigated. Functional decline is a common and serious problem in older hospitalized patients, resulting in a change in quality of life and lifestyle. Studies have shown that 30-60% of older people develop new dependencies in activities of daily living (ADL) during their hospital stay. Adverse health outcomes such as mortality, a prolonged hospital stay, nursing home placement and increased dependency of older people at home are the results. Not only are the personal costs high but also, in a rapidly growing older population, the impact on health-care costs is also high. Age, lower functional status, cognitive impairment, preadmission disability in instrumental activities of daily life (IADL), depression and length of hospital stay were identified as predictors of functional decline. Three screening instruments to identify hospitalized patients at risk for functional decline were found in the literature: the Hospital Admission Risk Profile, the Identification of Seniors at Risk and the Care Complexity Prediction Instrument. The reported validity was moderate. Reliability and the ease of use in the clinical setting were not well described. These three instruments should be further tested in a hospitalized older population. Screening is a first step to identify patients at risk for functional decline and this will make it possible to treat patients who are identified so as to prevent functional decline. Because of their ability to observe and to guide the patients and the overall view they have, nurses play a key role in this process.


Effects of an Enriched Extract of Paeoniflorin, a Monoterpene Glycoside used in Chinese Herbal Medicine, on Cholesterol Metabolism in a Hyperlipidemic Rat Model.
BACKGROUND Paeoniflorin is a monoterpene glycoside extracted from the roots of Paeonia lactiflora and is used in Chinese herbal medicine to treat hyperlipidemia. The aim of this study was to evaluate the effects of an enriched extract of paeoniflorin on cholesterol levels, hemodynamics, and oxidative stress in a hyperlipidemic rat model. MATERIAL AND METHODS Male Sprague-Dawley rats were fed high-cholesterol diets and treated with three different doses of paeoniflorin for 12 weeks. The effects of paeoniflorin treatment were assessed on cholesterol levels, cholesterol metabolism, red blood cell vascular flow using hemorheology, antioxidant enzymes, and expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR). Rat liver histology and immunohistochemical analysis were performed to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), cytochrome P450 7A1 (CYP7A1), and peroxisome proliferator-activated receptors (PPAR)-α. Protein expression HMG-CoAR, low-density lipoprotein receptor (LDLR), PPAR-α and CYP7A1 was measured by Western blotting. Antioxidant activity in rat liver was determined by measuring superoxide dismutase (SOD) and malondialdehyde (MDA). RESULTS Serum and hepatic cholesterol, hepatic steatosis and the products of cholesterol metabolism were reduced by paeoniflorin treatment, which also reduced the activity of HMG-CoAR and upregulated the expression of LDLR, PPAR-α, and CYP7A1 expression, increased SOD, decreased MDA, and upregulated Nrf2 expression. CONCLUSIONS The findings of this study in a rat model of hyperlipidemia have shown that paeoniflorin regulates hepatic cholesterol synthesis and metabolism and may also protect the liver from oxidative stress.


Experience-dependent plasticity in the mushroom bodies of the solitary bee Osmia lignaria (Megachilidae).
All members of the solitary bee species Osmia lignaria (the orchard bee) forage upon emergence from their natal nest cell. Conversely, in the honey bee, days-to-weeks of socially regulated behavioral development precede the onset of foraging. The social honey bee's behavioral transition to foraging is accompanied by neuroanatomical changes in the mushroom bodies, a region of the insect brain implicated in learning. If these changes were general adaptations to foraging, they should also occur in the solitary orchard bee. Using unbiased stereological methods, we estimated the volume of the major compartments of the mushroom bodies, the neuropil and Kenyon cell body region, in adult orchard bees. We compared the mushroom bodies of recently emerged bees with mature bees that had extensive foraging experience. To separate effects of general maturation from field foraging, some orchard bees were confined to a cage indoors. The mushroom body neuropil of experienced field foragers was significantly greater than that of both recently emerged and mature caged orchard bees, suggesting that, like the honey bee, this increase is driven by outdoor foraging experience. Unlike the honey bee, where increases in the ratio of neuropil to Kenyon cell region occur in the worker after emerging from the hive cell, the orchard bee emerged from the natal nest cell with a ratio that did not change with maturation and was comparable to honey-bee foragers. These results suggest that a common developmental endpoint may be reached via different development paths in social and solitary species of foraging bees.


The impact and importance of resistance.
Bacterial resistance to antibiotics began to emerge soon after their introduction. Beginning in the 1970s, Propionibacterium acnes also began to show decreased sensitivity to the antibiotics typically used in acne management. Clinically, this trend has translated to decreased efficacy and even nonresponse to therapy. A variety of recommendations regarding optimum use of antibiotics in acne management have been developed to preserve the utility of these drugs. Most important is the use of combination therapy with benzoyl peroxide (BPO) to help minimize the development of resistance. Retinoids also are recommended in acne therapeutic regimens because these agents are active against most acne pathogenetic mechanisms, but they have no apparent activity preventing antibiotic resistance when used in combination with a topical antibiotic.


Delayed wraparound abdominal flap reconstruction for a totally degloved hand.
Resurfacing a totally degloved hand is one of the most difficult management problems in hand surgery. It is difficult to cover the entire hand by using flaps. Although early coverage can be achieved, secondary amputation is often required due to an inadequate blood supply. We devised a delayed wraparound abdominal flap (DWAF) that was well-vascularised and could cover the whole hand. Here we report on a patient with a totally degloved hand, in whom reconstruction was performed using a DWAF and good functional results were achieved despite late surgery. Reconstruction with a DWAF may be a useful option for the totally degloved hand.


Antigen recognition and activation of ovine gamma delta T cells.
We have investigated several aspects of gamma delta T cells in sheep. gamma delta T cells of sheep express a unique transmembrane protein termed T19 but lack the expression of particular cell-surface molecules such as CD2, CD4 and CD8 which are typically associated with alpha beta T cells. The majority of gamma delta T cells isolated from animals of all ages examined lacked the expression of CD45RA. A faster rate of activation by gamma delta T cells compared to either CD4 or CD8 T cells was seen in the time-course of IL-2 receptor alpha chain (CD25) cell-surface expression. All gamma delta T cells expressed the CD25 protein within 8 hr of activation whereas the majority of CD4 or CD8 T cells did not express CD25 until 24 hr post-concanavalin A (Con A) stimulation. This difference in the rate of expression of activation molecules was not restricted to CD25, as a similar trend was seen with cell-surface expression of major histocompatibility complex (MHC) class II molecules. We have used the distinct phenotypic profile of ovine gamma delta T cells to purify these cells by positive selection via the T19 molecule to assess their in vitro proliferative response to various antigens. Routinely, cell populations comprising more than 93% gamma delta T cells with yields of approximately 55% were obtained. Purified gamma delta T cells were capable of responding to Mycobacterium tuberculosis antigen in a primary and secondary in vitro proliferation assay and to ovalbumin in a secondary response. Ovine gamma delta T cells showed little, if any, proliferative response to allogeneic stimulator cells.


"Scarless" Inguinal Herniorrhaphy.
Laparoscopic inguinal herniorrhaphy is widely accepted. Robotic-assisted surgery provides improved 3-dimensional visualization and enhanced dexterity. The purpose of this case series was to demonstrate the feasibility of a modified, robotic, single-site, unilateral inguinal herniorrhaphy. Six patients 18 years of age or older with a body mass index <35 provided informed consent and underwent hernia repair with a modified herniorrhaphy technique from January to July 2014. Eight patients were screened and six case experiences are described in this series. The da Vinci Si robot, gel port, and instruments (Intuitive Surgical, Sunnyvale, California, USA) were used. With the patient in Trendelenburg position, a 25-mm incision was made within the umbilicus. The fascia was incised, and the peritoneal cavity was entered. A robotic cholecystectomy gel port was placed. Robotic instruments were inserted, and the robot was docked. A preperitoneal flap was raised on the affected side with the robotic instruments used interchangeably. The hernia sac was identified and reduced, and the mesh was tacked in place. The preperitoneal flap was tacked back in place. The robot was undocked, the abdomen was desufflated, and the fascia was closed. Single-site unilateral inguinal herniorrhaphy was performed for 6 patients. All patients were discharged the same day, had good aesthetic results, and experienced no hernia recurrence. Robotic single-site gel port inguinal herniorrhaphy is feasible and appears as safe and time efficient as laparoscopic herniorrhaphy in this small group.


Inverse design of a spatial filter in edge enhanced imaging.
A spatial filter, as a key element in edge enhanced imaging, determines the resolution and the contrast of imaging. However, the conventional spiral phase filter (SPF) results in background noise near the edges of objects in the formed images due to the fact that the point spread function (PSF) of the SPF has sub-oscillations that decrease the edge resolution. In this Letter, we propose a method for inversely designing the spatial filter, aiming to achieve high-resolution images. We show that the sub-oscillations in the PSF of the filter can be, in principle, completely suppressed. Further, we experimentally demonstrate the edge enhancement, with high resolution, for both amplitude and phase objects by using our own designed filter. Our method may find potential applications in fingerprint identification and image processing.


15-Epi-16-(para-fluorophenoxy)-lipoxin A(4)-methyl ester, a synthetic analogue of 15-epi-lipoxin A(4), is protective in experimental ischemic acute renal failure.
Lipoxins are endogenous lipoxygenase-derived eicosanoids, generated during inflammatory, hypersensitivity, and vascular events, that display vasodilatory, antiinflammatory, and pro-resolution activity. Here, we evaluated the efficacy of 15-epi-16-(para-fluorophenoxy)-lipoxin A(4)-methyl ester (15-epi-16-(FPhO)-LXA(4)-Me), a stable synthetic analogue of aspirin-triggered 15-epi-lipoxin A(4) in ischemic acute renal failure (ARF) in NIH Swiss mice. ARF was induced by 30-min crossclamping of renal pedicles and was associated with elevated serum creatinine, morphologic injury, polymorphonuclear leukocyte (PMN) recruitment, and increased mRNA levels for adhesion molecules (intercellular adhesion molecule-1 [ICAM-1] and vascular cell adhesion molecule-1 [VCAM-1]), chemokines (growth regulated oncogene-1 [GRO1]), and cytokines (interleukin-1beta [IL-1beta] and IL-6) after 24-h reperfusion. A single bolus of 15-epi-16-(FPhO)-LXA(4)-Me afforded striking functional (mean +/- SEM creatinine in mg/dl: sham-operated, 0.77 +/- 0.04; ARF + vehicle, 2.49 +/- 0.19; ARF + 15-epi-16-(FPhO)-LXA(4)-Me, 0.75 +/- 0.12; P < 0.001) and morphologic protection and reduced PMN infiltration. Treatment with 15-epi-16-(FPhO)-LXA(4)-Me was also associated with lower IL-1beta, IL-6, and GRO1 mRNA levels, whereas ICAM-1 and VCAM-1 mRNA levels were unchanged. Compatible with these results, LXA(4) blunted chemoattractant-stimulated PMN migration across HK-2 renal epithelial cell monolayers in vitro, but it did not inhibit cytokine-induced HK-2 ICAM-1 expression or adhesiveness for PMN. Interestingly 15-epi-16-(FPhO)-LXA(4)-Me-treated animals also displayed increased renal mRNA levels for suppressors of cytokine signaling-1 (SOCS-1) and SOCS-2, but not CIS-1, endogenous inhibitors of cytokine-elicited Jak/Stat-signaling pathways. These results indicate that 15-epi-16-(FPhO)-LXA(4)-Me is protective in renal ischemia reperfusion injury in vivo, at least partially by modulating cytokine and chemokine expression and PMN recruitment, and provides a rationale for further exploration of the efficacy of LXA(4) structural analogues in ischemic ARF and other renal diseases.


Small plot evaluation of a sustained-release sand granule formulation of methoprene (SAN 810 I 1.3 GR) for control of Aedes Taeniorhynchus.
A sand granule formulation of methoprene (SAN 810 I 1.3 GR) was tested in outdoor intermittently flooded pools as a pre- and postflood treatment for the control of Aedes taeniorhynchus. In field test 1, pre- and postflood treatments were equally effective. Inhibition of emergence in mosquitoes exceeded 90% for one and 3 flood/dry cycles when SAN 810 I 1.3 GR was applied at rates of 2.8 and 5.6 kg/ha, respectively. In field test 2, > 90% inhibition of emergence was achieved only when SAN 810 I 1.3 GR was applied postflood at 5.6 kg/ha.


Clinical features of early haemarthroses in severely affected adolescent haemophiliacs.
Six hundred and ninety bleeds into the knees, ankles and elbows of severe haemophiliacs presenting for treatment within 3 h of the onset of symptoms have been studied with the aim of providing clinical information for the haemophiliac patient or his parent treating early bleeding episodes at home. Patients were resident at a boarding school and documentation and follow-up to complete resolution was possible. Stiffness was a presenting symptom in 61% of elbow bleeds, 49% of knee bleeds and 18% of ankle bleeds. Pain was a presenting feature in 79% of ankle bleeds, 55% of knee bleeds and 42% of elbow bleeds. Tenderness was a common feature of ankle bleeds (85%), less so in elbows (55%) and knees (69%). Swelling was a very common feature at all sites and the mean increases in girth of the knees, elbows and ankles were 1.42 cm, 0.88 cm, and 0.62 cm, respectively. All the knee and elbow bleeds and 85% of the ankle bleeds had demonstrable restriction of movement. There was a direct relationship between the degree of swelling, extent of movement restriction and time taken for complete restoration of function, the mean of which was 3.6 days for elbows, 2.5 for knees and 1.1 for ankles.


Motivational Interviewing As an Adjunct to Periodontal Therapy-A Systematic Review.
Aim: Periodontal therapy is highly dependent on a patient's long-term adherence with regard to oral hygiene, diet, and regular check-ups at the dentist. Motivational Interviewing (MI) is a client-centered, directive method for encouraging a patients' behavioral health change. The aim of this systematic review was to reveal the effects of MI as an adjunct to periodontal therapy. Methods: Three databases (PubMed, Cochrane Library, and Web of Science) were reviewed for randomized controlled clinical trials. Articles were included when using MI as an adjunct to periodontal therapy and presenting clinical periodontal and oral hygiene related parameters. Two authors independently coded the relevant articles. Results: The search yielded 496 articles. After analysis and exclusion, a total of five papers could be included. The quality of the articles ranged between 72-88%. The two independent raters showed a high inter-rater reliability (Cohens-Kappa = 0.89). In two studies MI showed a significant positive effect on bleeding on probing and plaque values. One study showed improvement of self-efficacy in interdental cleaning. Two studies showed no influence of MI on periodontal parameters of the patients. Conclusion: The use of MI as an adjunct to periodontal therapy might have a positive influence on clinical periodontal parameters (plaque values, gingival, and periodontal inflammation) and psychological factors related to oral hygiene (self-efficacy). Due to the low body of evidence further studies are needed. Future studies should include fidelity measures of the applied MI, a high number of counselors, several MI sessions, and long-term study follow-up to show potential effects.


Reversal of T cell anergy in leprosy patients: in vitro presentation with Mycobacterium leprae antigens using murabutide and Trat peptide in liposomal delivery.
Mycobacterium leprae, the causative agent of leprosy resides and multiplies within the host monocytes and macrophages, thereby evading host immune system. Cell-mediated immune response (CMI) plays a vital role as evidenced from the high CMI in BT/TT (borderline and tuberculoid) patients and conversely low in BL/LL (borderline and lepromatous) patients. In the present study, an attempt was made to immunomodulate the anergized T cells of lepromatous leprosy patients by presenting the mycobacterial antigen in combination with T cell adjuvant, murabutide (active analog of muramyl' dipeptide, MDP-BE) and a Trat peptide (T cell epitope of Integral membrane protein (Trat) from Escherichia coli) in particulate form (liposomes) or soluble form (media). PBMNC of normal, BT/TT and BL/LL were stimulated in vitro with five mycobacterial antigens (Ag) in the following formulations, Ag, Ag+murabutide, Ag+murabutide+Trat peptide either in liposomes or in medium. All the five antigen(s) when delivered in liposomes containing murabutide and Trat peptide showed a very high lymphoproliferative response (p<0.001) in all the three groups. IFN-gamma and IL-2 were significantly (p<0.001) high in these culture supernatants compared to IL-10 and IL-4 confirming a shift from CD4+Th2 to Th1 response in leprosy patients with particulate mode of antigen presentation. Interestingly, PBMNC derived from lepromatous patients also showed consistent T cell proliferation with all the formulations. Further, the mechanism of liposomal processing of antigens was studied using different inhibitors that interfere at different stages of antigen presentation. Results indicate that this study may pave way for an immunotherapeutic approach for reverting the anergic T cells of lepromatous patients to proliferating T cells with the release of Th1 cytokines thereby restoring the CMI response in these patients.


Strong indirect coupling between graphene-based mechanical resonators via a phonon cavity.
Mechanical resonators are promising systems for storing and manipulating information. To transfer information between mechanical modes, either direct coupling or an interface between these modes is needed. In previous works, strong coupling between different modes in a single mechanical resonator and direct interaction between neighboring mechanical resonators have been demonstrated. However, coupling between distant mechanical resonators, which is a crucial request for long-distance classical and quantum information processing using mechanical devices, remains an experimental challenge. Here, we report the experimental observation of strong indirect coupling between separated mechanical resonators in a graphene-based electromechanical system. The coupling is mediated by a far-off-resonant phonon cavity through virtual excitations via a Raman-like process. By controlling the resonant frequency of the phonon cavity, the indirect coupling can be tuned in a wide range. Our results may lead to the development of gate-controlled all-mechanical devices and open up the possibility of long-distance quantum mechanical experiments.


[The nursing experience in helping an unmarried adolescence girl to care for her premature infant].
This case study describes the author's experience in helping an unmarried adolescent girl learn to take proper care of her premature infant. Primary data were collected by observing interactions as well as from face-to-face and telephone interviews. Roy's model, family structure and the APGAR family function assessment theory were used to analyze data. Major problems identified included: alteration of family function, potential risk of parent/infant attachment and insufficient knowledge on the part of the mother regarding childcare. During the course of this study, the author served in a variety of roles including caregiver, educator and support-giver to the adolescent mother as well as provided training on in-home use of the Kangaroo technique for premature births. Maintaining a non-judgmental attitude and providing encouragement to the adolescent mother were essential to the success of assistance efforts. The establishment of an adolescent obstetrics outpatient service with social work intervention, discharge services and home visits by community nurses may be necessary in order to achieve holistic care goals.


[Collecting, publishing and searching scientific and research information].
Time of information in which we live resulted in the increase of the amount of the information exponential growth of the new kind of knowledge, flourishing of the familiar ones, and the appearance of the new sciences. Medical (health) informatics occupies the central place in all the segments of modern medicine in the past thirty years--in practical work, education and scientific research. In all that, computers have taken over the most important role and are used intensively for the development of the health information systems. Following activities develop intensively within the area of health informatics: health- documentation, health-statistics, health-informatics and biomedical scientific and professional information. Starting with the fact that in this century and especially after the World War II, great advancement in bio-medical sciences is visible, in Bosnia and Herzegovina, it is clear that as a result of the above increase in scientific research, in the number of scientists, and funds invested in scientific institutions, equipment and documentation, is visible. Innovations and developments in science demand analytic-synthetic processing of scientific information and their utilisation research. This can be realised by collecting sources (documents) for reading, noting, editing, discovering-which is the integral part of scientific developmental research. Scholarly journals as well as the publications that follow the latest events in the world of science, and inform their users in the area of bio-medicine quickly and efficiently, play an important role in the professional literature.


Partnership of Arthrobacter and Pimelobacter in Aerobic Degradation of Sulfadiazine Revealed by Metagenomics Analysis and Isolation.
In this study, metagenomic analyses were combined with cultivation-based techniques as a nested approach to identify functionally significant bacteria for sulfadiazine biodegradation within enrichment communities. The metagenomic investigations indicated that our previously isolated sulfadiazine degrader, Arthrobacter sp. D2, and another Pimelobacter bacterium concomitantly occurred as most abundant members in the community of an enrichment culture that performed complete sulfadiazine mineralization for over two years. Responses of the enriched populations to sole carbon source alternation further suggested the ability of this Pimelobacter member to grow on 2-aminopyrimidine, the most prominent intermediate metabolite of sulfadiazine. Taking advantage of this propensity, additional cultivation procedures have enabled the successful isolation of Pimelobacter sp. LG209, whose genomic sequences exactly matched that of the dominant Pimelobacter bacterium in the sulfadiazine enrichment culture. Integration of metagenomic investigations with the physiological characteristics of the isolates conclusively demonstrated that the sulfadiazine mineralization in a long-running enrichment culture was prominently mediated by primary sulfadiazine-degrading specialist strain Arthrobacter sp. D2 in association with the 2-aminopyrimidine-degrading partner strain Pimelobacter sp. LG209. Here, we provided the first mechanistic insight into microbial interactions in steady sulfadiazine mineralization processes, which will help develop appropriate bioremediation strategies for sulfadiazine-contaminated hotspot sites.


Usefulness of Dermoscopy to Provide Accurate Assessment of Skin Cancers.
Seborrheic keratosis (SK) is the most common benign tumour of epidermal origin. In most cases, it is simple to recognize in the clinical examination. However, sometimes SK can be a problematic lesion. We present the cases of two patients with seborrheic keratosis in whom we diagnosed the skin cancer through dermoscopic and histopathological examinations. The article aims to draw attention to the need for dermoscopic examinations to be included for an accurate assessment of the nevi not only by dermatologists but also not-specialized doctors. We would like to underline that many skin cancers share the similar features of malignancy, and competence and capability to interpret the dermoscopic pictures correctly are important for early recognition of malignant lesion. Very often malignant skin cancers can be hidden among benign lesions like seborrheic keratosis or they can be imitators of benign lesions. Amongst all cases of imposing SK, basal cell carcinoma, squamous cell carcinoma, melanoma is the most important differential diagnosis, of which their dermoscopic features will be discussed in this article.


Extended medial gastrocnemius myocutaneous flap in repair of the quadriceps extension mechanism.
The gastrocnemius muscle is versatile in flap repair of defects from anterior knee to lower leg. We describe a case of extensor reconstruction using an extended medial gastrocnemius myocutaneous flap. A medial gastrocnemius flap was raised distal to its musculotendinous insertion. At its point of rotation, it was anchored to the anterior periosteum of the tibia, hence obliterating dead space and recreating the extensor mechanism of the knee. The patient had no flap loss and was able to ambulate independently. He showed no extensor lag. Our flap is unique in that it is the only medial gastrocnemius flap that has shown no extensor lag as well as complete flexion of the knee following a disrupted entire quadriceps mechanism. It is also the first myocutaneous gastrocnemius flap that has been described for this purpose.


Sexual function changes during the 5 years after high-dose treatment and hematopoietic cell transplantation for malignancy, with case-matched controls at 5 years.
This prospective study evaluated sexual function through 5 years after myeloablative allogeneic hematopoietic cell transplantation (HCT) for cancer to determine sexual function recovery and residual problems. Adults completed measures before HCT (N = 161), with survivors followed at 6 months and at 1, 2, 3, and 5 years. At 5 years case-matched controls also completed assessments. Analyses indicated that men and women differed in rates of being sexually active across time (P < .001) and in overall sexual function (P < .001). Both sexes declined in sexual activity rates and sexual function from before HCT to 6 months afterward (P < or = .05). Activity rates recovered for men by 1 year (74%) and for women by 2 years (55%). Men improved from their 6-month nadir in sexual function by 2 years (P = .02), whereas women did not improve by 5 years (P = .17). Both male and female survivors were below controls in rates of sexual activity and sexual function at 5 years. Most women reported sexual problems (80% of survivors vs 61% of controls, P = .11); in contrast for men 46% of survivors versus 21% of controls (P = .05) reported problems. Thus, despite some recovery, sexual dysfunction remained a major problem for men and women after HCT. Aggressive efforts are needed to treat these deficits.


Infectious Neuropathies.
This article discusses the clinical manifestations and management of infectious peripheral neuropathies. Several infectious etiologies of peripheral neuropathy are well-recognized and their treatments are firmly established. The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with several central and peripheral nervous system manifestations, including peripheral neuropathies. Additionally, some COVID-19 vaccines have been associated with Guillain-Barré syndrome. These disorders are an active area of surveillance and research. Recent evidence-based guidelines have provided updated recommendations for the diagnosis and treatment of Lyme disease. Infectious agents of many types (primarily bacteria and viruses) can affect the peripheral nerves, resulting in various clinical syndromes such as mononeuropathy or mononeuropathy multiplex, distal symmetric polyneuropathy, radiculopathy, inflammatory demyelinating polyradiculoneuropathy, and motor neuronopathy. Knowledge of these infections and the spectrum of peripheral nervous system disorders associated with them is essential because many have curative treatments. Furthermore, understanding the neuropathic presentations of these disorders may assist in diagnosing the underlying infection.


Everolimus-eluting stents versus sirolimus-eluting stents in patients with cardiac allograft vasculopathy.
Cardiac allograft vasculopathy remains one of the most important factors leading to chronic cardiac allograft rejection. When revascularization is needed percutaneous coronary interventions are the method of choice. To compare the short- and long-term outcomes of cardiac allograft vasculopathy patients treated with everolimus- (EES) or sirolimus-eluting stents (SES). Between December 2012 and December 2020, 319 patients after heart transplantation undergoing coronary angiography at our institution were analysed. Subsequently 39 patients underwent de novo angioplasty with second-generation EES. The primary study endpoint was angiographic restenosis as evaluated by quantitative coronary angiography. Secondary outcomes included binary restenosis, target lesion revascularization and cardiac death during the follow-up period (6 months). Twenty-four patients were treated with EES and 15 treated with SES. No significant differences were observed regarding the rate of risk factors of cardiovascular diseases and comorbidities. The patients treated with EES were younger (55.8 ±11.8 vs. 60.1 ±12.2) and less frequently male (79% vs. 93%). The majority of patients were diagnosed with single vessel disease with LAD involvement (62% and 86% in the EES group, and 47% and 56% in the SES group). In 6 months follow-up, late lumen loss was comparable in both groups, 0.19 ±0.15 vs. 0.14 ±0.15, and binary restenosis was 4% and 0% for EES and SES groups, respectively. Second generation drug-eluting stents eluting rapamycin analogues are associated with high direct efficacy of procedures and low incidence of restenosis in a 6-month follow-up.


Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1c) receptors.
Serotonin (5-HT)-stimulated phosphoinositide hydrolysis is mediated by the 5-HT-2 receptor in rat cerebral cortex and by the 5-HT-1c receptor in rat choroid plexus. These systems were used to determine relative efficacies of piperazine derivatives at the 5-HT-2 and 5-HT-1c receptors. Both quipazine and 6-chloro-2-[1-piperazinyl]-pyrazine (MK-212) stimulated phosphoinositide hydrolysis in cerebral cortex, and these effects were blocked by ketanserin. The maximum responses to these agonists were 80% of the maximum response to 5-HT. m-Trifluoromethylphenylpiperazine (TFMPP), m-chlorophenylpiperazine (MCPP) and 1-(1-naphthyl)-piperazine (1-NP) did not stimulate phosphoinositide hydrolysis in cerebral cortex at concentrations that blocked the effect of 5-HT. In the choroid plexus, TFMPP and MCPP, as well as MK-212 and quipazine, increased phosphoinositide hydrolysis and mianserin blocked these effects. MK-212 had an efficacy which was equal to that of 5-HT, whereas quipazine, MCPP and TFMPP were partial agonists in the choroid plexus. 1-NP did not stimulate phosphoinositide hydrolysis in choroid plexus but completely blocked the effect 5-HT. On the basis of these data, we conclude that quipazine and MK-212 are partial agonists at 5-HT-2 receptors in cerebral cortex, whereas 1-NP, TFMPP and MCPP are pure antagonists of the cortical 5-HT-2 receptor. However, TFMPP and MCPP as well as quipazine and MK-212 are agonists at the 5-HT-1c receptor, while 1-NP is a pure antagonist of the 5-HT-1c receptor in choroid plexus.


A novel amino acid glycoside and three amino acids from Allium sativum.
A novel amino acid glycoside (-)-N-(1'-deoxy-1'-beta-D-fructopyranosyl)-S-allyl-L-cysteine sulfoxide [1], was isolated from a hydrophilic extract of the leaves of Allium sativum (Alliaceae), together with three known compounds: (+)-S-allyl-L-cysteine sulfoxide [2],(+)-S-methyl-L-cysteine sulfoxide [3], and (+)-S-(trans-1-propenyl)-L-cysteine sulfoxide [4]. The latter two substances were isolated for the first time from garlic. The structure elucidation of 1 was performed by extensive chemical, spectroscopic (ir, fabms, 1D and 2D(1)H- and (13)C-nmr measurements) and chromatographic experiments. For the first time, detailed nmr data and the unambiguous assignment of all (13)C-nmr data for compounds 2-4 were reported. Compound 1, the amino acid glycoside, revealed a significant inhibition of in vitro platelet aggregation induced by ADP and epinephrine, whereas none of the amino acids tested displayed any activity.


Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain.
Tramadol ER* is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. This study evaluated long-term safety of tramadol ER and effectiveness outcomes in the management of chronic, nonmalignant pain. Patients enrolled directly for approximately 1 year of open-label tramadol ER treatment if they had chronic, nonmalignant pain (n = 919), or 'rolled over' for 38 weeks of open-label tramadol ER treatment if they completed either of two 12-week, placebo-controlled studies of tramadol ER for low back pain (n = 72) or osteoarthritis (n = 61). Tramadol ER was titrated to a dose of 300 mg once daily (patients >or= 75 years) or 300-400 mg once daily (patients < 75 years). A total of 257 (24%) patients completed the study. Common adverse events, regardless of treatment relationship, were nausea, dizziness (excluding vertigo), and constipation. Mean scores for current pain intensity (from 0 = no pain to 100 = extreme pain) and least, worst, and average pain intensity over the past week improved at every post-baseline visit. At each post-baseline visit, > 50% of patients provided a global assessment rating of good, very good, or excellent. Study limitations were mandatory titration to 400 mg in some patients, concomitant analgesic therapy as a confounding variable, and lack of a placebo comparator. Individualized dose titration and limiting once-daily therapy with tramadol ER to the maximum recommended daily dose of 300 mg may balance tolerability and analgesic effects of tramadol ER in patients with chronic, nonmalignant pain.


Specific and nonspecific multiple unit activities during the onset of pentylentetrazol seizures. I. Intact animals.
A quantitative evaluation of specific and nonspecific multiple unit activity (MUA) before and during pentylenetetrazol-induced EEG tonic-clonic discharges (OTCD) was made at four levels of the CNS: cortical, thalamic, mesencephalic, and pontine. In addition, MUA of sciatic nerve was recorded to detect possible spinal cord efferent discharges. At all levels, sustained increase in specific and nonspecific multiple unit activity preceded EEG and sciatic nerve discharges induced by pentylenetetrazol. Increments in nonspecific MUA occurred sooner and were larger than those of specific MUA, and increments in mesencephalic nonspecific MUA occurred sooner and were larger than those of other cortical, thalamic, and pontine nonspecific MUAs. This sequence of neuronal activation suggests that pentylenetetrazol seizures are initiated in nonspecific structures at the mesencephalic level.


The actor-director and patient-therapist relationships: a process comparison.
The relationship between the actor and director, like that between the patient and psychotherapist, relies on intense emotional involvement. Both demand sensitivity, reciprocity, and a deep understanding of human behavior. Because dramatic action is created through continuous conflict between characters, actors must explore not only their actions, but also the reactions of those with whom they are in relationship. The process of therapy is equally interdependent. Through the relationship, therapists provide a context in which their patients can work through their conflicts. As in the rehearsal process, actions are explored in a supportive environment. This paper has presented a process comparison of the actor-director and patient-therapist relationships by proposing that both are art forms that rely on the skill of a trusted facilitator. Some of the techniques explored include: empathic attunement, emotional recall, transference, overcoming performance obstacles, improvisation, risk-taking, the pleasure principle, and creating a sense of family through new object relations. Like therapists, directors never forget that their work cannot be performed alone; it depends on interaction with the most delicate of phenomena: the human soul.


Analysis of the forearm rotational efficiency in extant hominoids: new insights into the functional implications of upper limb skeletal structure.
The greatly diversified locomotor behaviors in the Hominoidea impose different mechanical requirements in the upper limb of each species. As forearm rotation has a major role in locomotion, the skeletal structures involved in this movement may display differences among taxa that reflect functional adaptations. To test this, we use a biomechanical model that quantifies the rotatory capacity of pronator teres (rotational efficiency) from skeletal measurements. Using a large sample of hominoids, we aim to identify the morphological adaptations that confer differences in the mechanics of forearm motion and to assess the functional advantage of these adaptations. Forearm positions along the pronation-supination range where rotational efficiency is maximal depend on the orientation of the humeral medial epicondyle and differ among taxa. Our results indicate that these are related to locomotor mode. Knuckle-walkers exhibit a medial epicondyle more posteriorly directed, which, in elbow angles close to extension, causes rotational efficiency to be maximal in pronated positions of the forearm. Species with a significant amount of arboreal locomotion, such as vertical climbing, i.e., Pongo spp., Pan troglodytes and Gorilla gorilla, display more proximally oriented epicondyles, which, in elbow flexion, leads to maximum rotational efficiencies in supinated positions of the forearm. Hylobatidae, with the less posteriorly and proximally oriented epicondyle, show their maximum rotational efficiencies closer to the forearm neutral position throughout most of the flexion-extension range, which may be linked to brachiation in this taxon. In humans, the epicondylar orientation and thus the positions of the maximum rotational efficiencies fall between arboreal and terrestrial hominoids. This may be related to the enhanced manipulative skills of the upper limb. In conclusion, the current analysis indicates that the orientation of the humeral medial epicondyle is linked to the locomotor habits of extant hominoids and therefore can be used for locomotor inferences in fossil taxa.


One-pot strategy to simultaneously prepare dyed, flame retardant and UV-resistant silk fabric based on a safflower yellow derivative.
To give silk fabric multiple functions and improve its application range, a facile and eco-friendly one-pot technique was used to endow silk fabric with dyeing, flame retardant and ultraviolet (UV)-resistant performance based on a safflower yellow derivative. The structure, surface morphology, elemental composition, thermal properties and combustion behavior of the silk samples before and after modification were all characterized. In addition, the color depth and color fastness of the dyed silk (D-silk) and flame retardant silk (FR-silk) were evaluated and measured. The positive b* value in the CIELAB color space defined the yellow color of the dyed silk fabric. The char residue increased from 2.9 wt% of the original sample to 17.4 wt% of the FR-silk at 800 °C in air atmosphere. The limiting oxygen index (LOI) of FR-silk increased from 23.3% of the control sample to 32.8% with an increase of 40.7%. The peak of heat release rate (pHRR) and total heat release (THR) of FR-silk were much lower than that of the original sample. Furthermore, the UV protection factor (UPF) of FR-silk was 73.79, indicating excellent UV-resistance properties. The preparation process was green and environment-friendly, and the FR-silk had a good application prospect.


Effects of a Hot-Water Extract of Allium hookeri Roots on Bone Formation in Human Osteoblast-Like MG-63 Cells In Vitro and in Rats In Vivo.
Allium hookeri is a wild herb found mainly in the Himalayas, growing at altitudes of 1400-4200 m. A. hookeri is widely consumed as a vegetable and herbal medicine in Asia, but its effects on bone health have not been reported previously. This study investigated the effects of a hot-water extract of A. hookeri roots on bone formation. The hot-water extract significantly increased the proliferation of in vitro human osteoblast-like MG-63 cells and the stimulatory effects on osteoblast differentiation were noticeably greater for the hot-water extract than for daidzein (a positive control), as reflected by alkaline phosphatase activity, collagen content, and mineral deposition. Expression of the bone-remodeling marker osteocalcin production and bone microstructural parameters were significantly improved in Sprague-Dawley rats in vivo after oral treatment with the hot-water extract compared with their control (saline-administered) counterparts. The chemical compounds of the hot-water extract were characterized by liquid chromatography-mass spectrometry, and alliin, sinapic acid, and ferulic acid, which exert beneficial effects on bone health, were identified. These findings indicate that A. hookeri can be used as a natural resource for increasing bone formation. This is the first report of the anabolic effects of A. hookeri extracts on bone formation in vitro and in vivo.


Determining the effect of neuro-linguistic programming techniques on the conflict management and interpersonal problem-solving skills of nurse managers: A mixed methods study.
This study, which used quantitative and qualitative design, was conducted to explore the effect of neuro-linguistic programming techniques on the conflict management and interpersonal problem-solving skills of nurse managers. Neuro-linguistic programming is among the methods that can enable managers to achieve the desired results in managing interpersonal problems and conflicts in an organisation. The research was carried out with a mixed methods approach. The Personal and Professional Characteristics Information Form, Interpersonal Problem-Solving Inventory and Rahim Organizational Conflict Inventory-II were applied to 41 nurse managers and nurses to collect quantitative data for the study. Semi-structured questionnaires were used to collect qualitative data in focus-group interviews held both before and 6 months after the training. As a result of the content analysis of the qualitative data, the nurse managers in the training group were found to have improved abilities to plan and increased flexibility, positiveness, happiness and motivation when compared to the nurse managers in the control group. Findings supporting these data were obtained in the analyses of interviews with nurses. Neuro-linguistic programming training can make a difference in terms of helping nurse managers to develop interpersonal problem- and conflict-solving skills. Nurse managers can use neuro-linguistic programming techniques for conflict management and interpersonal problem-solving occurring in their organizations. For this purpose, it is recommended that pregraduate and postgraduate neuro-linguistic programming training is provided to nurse managers.


Evaluating men with benign prostatic hyperplasia.
The clinical manifestations of benign prostatic hyperplasia (BPH) include lower urinary tract symptoms (LUTS), poor bladder emptying, urinary retention, detrusor instability, urinary tract infection, hematuria, and renal insufficiency. However, the majority of men with BPH present with LUTS only. Because LUTS can indicate a variety of conditions, evaluation of symptomatic men must first aim to identify or exclude BPH and, if present, assess its severity. It is important to assess symptom severity at baseline and during follow-up, using the American Urological Association Symptom Index or the International Prostate Symptom Score. Further testing can then be tailored to narrow the diagnosis and guide treatment decisions. Factors such as patient age and concomitant malignancy will also affect management, but the main goal of treatment remains the improvement of quality of life for the patient.


Considerations in vaccine patent protection.
This feature article discusses the basic principles of patentability as related to vaccine research, and outlines recent cases in the US and EU in which vaccine patents have been considered. Issues regarding eligibility for supplementary protection, as currently being considered by the Court of Justice of the EU, are also outlined, as well as the implications of such issues in protecting future vaccine research.


Comparison of alfetanil and ketamine in combination with propofol for patient-controlled sedation during fiberoptic bronchoscopy.
During fiberoptic bronchoscopy, propofol, ketamine, benzodiazepines, and opiates are most commonly used, alone or in combination for sedation. The aim of this study was to compare the clinical efficacy of propofol/ketamine with propofol/alfentanil for patient-controlled sedation (PCS) during fiberoptic bronchoscopy. Patients undergoing fiberoptic bronchoscopy were randomly assigned to receive either propofol/alfentanil (PA group; n = 138) or propofol/ketamine (PK group; n = 138) via a patient-controlled analgesia (PCA) device for sedation and analgesia. Changes in blood pressure, heart rate (HR), and oxygen saturation were monitored. Degree of patient and bronchoscopist satisfaction was evaluated using a 10-cm visual analog scale (VAS) (0 = extremely uncomfortable to 10 = extremely comfortable). After sedation, systolic arterial pressure (SAP) decreased in the PA group, but SAP was stable in the PK group. Compared with values immediately before starting bronchoscopy, SAP and HR increased during the procedure in both groups (P < 0.05). Patients in the PK group showed more satisfaction [(9.5 (6-10) vs. 9.0 (6-10)), P < 0.05] and amnesia (82% vs. 61%, P < 0.01). Despite these differences, the majority (greater than 90%) of the patients in both groups stated that they were comfortable during the procedure. Our results show that although both techniques proved effective for sedation in patients undergoing fiberoptic bronchoscopy, ketamine is superior to alfentanil when used in combination with propofol because of the high patient satisfaction and amnesia.


Computational Model of Antidepressant Response Heterogeneity as Multi-pathway Neuroadaptation.
Current hypotheses cannot fully explain the clinically observed heterogeneity in antidepressant response. The therapeutic latency of antidepressants suggests that therapeutic outcomes are achieved not by the acute effects of the drugs, but rather by the homeostatic changes that occur as the brain adapts to their chronic administration. We present a computational model that represents the known interactions between the monoaminergic neurotransmitter-producing brain regions and associated non-monoaminergic neurotransmitter systems, and use the model to explore the possible ways in which the brain can homeostatically adjust to chronic antidepressant administration. The model also represents the neuron-specific neurotransmitter receptors that are known to adjust their strengths (expressions or sensitivities) in response to chronic antidepressant administration, and neuroadaptation in the model occurs through sequential adjustments in these receptor strengths. The main result is that the model can reach similar levels of adaptation to chronic administration of the same antidepressant drug or combination along many different pathways, arriving correspondingly at many different receptor strength configurations, but not all of those adapted configurations are also associated with therapeutic elevations in monoamine levels. When expressed as the percentage of adapted configurations that are also associated with elevations in one or more of the monoamines, our modeling results largely agree with the percentage efficacy rates of antidepressants and antidepressant combinations observed in clinical trials. Our neuroadaptation model provides an explanation for the clinical reports of heterogeneous outcomes among patients chronically administered the same antidepressant drug regimen.


Distinct preoptic-BST nuclei dissociate paternal and infanticidal behavior in mice.
Paternal behavior is not innate but arises through social experience. After mating and becoming fathers, male mice change their behavior toward pups from infanticide to paternal care. However, the precise brain areas and circuit mechanisms connecting these social behaviors are largely unknown. Here we demonstrated that the c-Fos expression pattern in the four nuclei of the preoptic-bed nuclei of stria terminalis (BST) region could robustly discriminate five kinds of previous social behavior of male mice (parenting, infanticide, mating, inter-male aggression, solitary control). Specifically, neuronal activation in the central part of the medial preoptic area (cMPOA) and rhomboid nucleus of the BST (BSTrh) retroactively detected paternal and infanticidal motivation with more than 95% accuracy. Moreover, cMPOA lesions switched behavior in fathers from paternal to infanticidal, while BSTrh lesions inhibited infanticide in virgin males. The projections from cMPOA to BSTrh were largely GABAergic. Optogenetic or pharmacogenetic activation of cMPOA attenuated infanticide in virgin males. Taken together, this study identifies the preoptic-BST nuclei underlying social motivations in male mice and reveals unexpected complexity in the circuit connecting these nuclei.


[Efficacy comparison of subtotal colectomy with antiperistaltic cecoproctostomy and total colectomy with ileorectal anastomosis for patients with slow transit constipation].
To compare the efficacy between subtotal colectomy with antiperistaltic cecoproctostomy and total colectomy with ileorectal anastomosis (TAC-IRA) for patients with severe refractory slow transit constipation(STC). During 1999 to 2002, TAC-IRA was the preferred procedure for 20 STC patients in our department. From 2003 to 2005, 17 STC patients underwent subtotal colectomy plus antiperistaltic cecoproctostomy. Clinical data of the two groups were collected and compared retrospectively. There were no significant differences in basic preoperative clinical data between the two groups. During the follow-up period, the time of daily defecation in the antiperistaltic cecoproctostomy group was less than that of TAC-IRA group (2.4+/-0.9 vs 3.4+/-0.8, P=0.0014), meanwhile the Wexner continence score was significantly lower in the antiperistaltic cecoproctostomy group (4.3+/-1.8 vs 5.8+/-1.9, P=0.0223). Barium enema after subtotal colectomy showed that residual ascending colon and cecum presented a sign of "reservoir". Subtotal colectomy with antiperistaltic cecoproctostomy is a better method for appropriately selected patients with STC than TAC-IRA.


Increasing game prices may alter farmers' behaviours towards leopards (Panthera pardus) and other carnivores in South Africa.
Human-carnivore conflict occurs globally, particularly in regions where large carnivores predate livestock. Retaliatory killings do occur, and although predation of livestock by carnivores happens, losses from other factors such as disease or injury can be misattributed because of landowner perceptions. Game farming for both trophy hunting and eco-tourism is becoming increasingly common in South Africa, and there has been a rapid increase in the cost of game animals (in some species as much as five-fold) between 2010 and 2015. This could result in an increase in conflict between commercial game farmers and carnivores. We conducted two questionnaire surveys of farmers in 2010 and 2015 to investigate this. We asked if there had been changes in farming practices, perceived predator activity, perceived amount of livestock and commercial game losses, and actions taken towards carnivores in a South African farming community. We found no significant change in farming types in the area or losses of livestock between the years. However, there was a significant increase in perceived commercial game losses reported, even though protection of game had increased. Actions taken towards carnivores by livestock/game farmers were also significantly more negative in 2015 compared to farmers growing crops, but there was no such difference in 2010. We suggest that these changes could be a result of the increase in game prices over that period, leading to greater financial losses when an animal is predated, which in turn could increase the likelihood of retaliatory killings of carnivores.


Cytotoxic CD4 T cells in the mucosa and in cancer.
CD4 T cells were initially described as helper cells that promote either the cellular immune response (Th1 cells) or the humoral immune response (Th2 cells). Since then, a plethora of functionally distinct helper and regulatory CD4 T cell subsets have been described. CD4 T cells with cytotoxic function were first described in the setting of viral infections and autoimmunity, and more recently in cancer and gut dysbiosis. Regulatory CD4 T cell subsets such as Tregs and T-regulatory type 1 (Tr1) cells have also been shown to have cytotoxic potential. Indeed, Tr1 cells have been shown to be important for maintenance of stem cell niches in the bone marrow and the gut. This review will provide an overview of cytotoxic CD4 T cell development, and discuss the role of inflammatory and Tr1-like cytotoxic CD4 T cells in maintenance of intestinal stem cells and in anti-cancer immune responses.


Impact of a New Portable Air Purification Technology Device in the Pediatric Hospital Setting - A Pre-post Assessment Study.
Introduction We assessed whether portable photo-electrochemical oxidation (PECO) air purification in the pediatric hospital room setting could improve health outcomes for patients admitted with respiratory distress. Methods We performed a prospective study evaluating the use of a portable air purifier with PECO technology. The historical control group comprised matched patients. Twenty-seven PECO-equipped portable air filtration devices were placed in the rooms. Clinical endpoints included length of stay in the hospital, length of stay in the intensive care unit (ICU), rates of intubation, non-invasive ventilation, and nebulizer use. Results The mean length of ICU stay was 0.7 days in the pre-intervention period and decreased to 0.4 days post-intervention. The mean length of overall hospitalization reduced by 0.3 days. The rate of non-invasive ventilation use was 77% in the pre-intervention period and decreased to 23% in the post-intervention period. The rate of nebulizer use was 59% in the pre-intervention period and 41% in the post-intervention period. The rate of intubation was 57.1% in the pre-intervention period and 43% in the post-intervention period. Conclusion Portable PECO air purification may reduce hospital length of stay, rates of intubation, and need for non-invasive intervention and nebulizers for pediatric patients admitted with respiratory distress.


Refractory cold agglutinin disease successfully treated with daratumumab. A case report and review of literature.
Cold agglutinin disease (CAD) is immune-mediated hemolytic anemia. The disease is caused by cold reactive autoantibodies that induce hemolysis through the activation of the complement pathway. Most patients with CAD are elderly, and half may have refractory CAD that may not respond to the first-line treatment option (i.e. rituximab). Some cases are refractory to multiple lines of therapy, including chemotherapeutic agents, which might be toxic, especially for elderly patients. Daratumumab is a human monoclonal antibody targeting CD 38 glycoprotein, a transmembrane protein highly expressed in lymphoid and plasma cells. Daratumumab is currently approved for treating multiple myeloma and is used mainly as a combination therapy with other agents. Our patient is a 69-year-old female diagnosed with CAD after presenting with severe anemia and significant circulatory symptoms. Rituximab was not effective in controlling her disease, and she refused other available chemotherapeutic agents due to their side effects profile. We used daratumumab combined with erythropoietin, which led to a dramatic response measured by stabilizing her hemoglobin levels and transfusion independence. Our case is the third reported case of refractory CAD successfully treated with daratumumab, which suggests that daratumumab might be a potential agent for the treatment and control of refractory Cold Agglutinin Disease.


Enhance the performance of current scoring functions with the aid of 3D protein-ligand interaction fingerprints.
In structure-based drug design, binding affinity prediction remains as a challenging goal for current scoring functions. Development of target-biased scoring functions provides a new possibility for tackling this problem, but this approach is also associated with certain technical difficulties. We previously reported the Knowledge-Guided Scoring (KGS) method as an alternative approach (BMC Bioinformatics, 2010, 11, 193-208). The key idea is to compute the binding affinity of a given protein-ligand complex based on the known binding data of an appropriate reference complex, so the error in binding affinity prediction can be reduced effectively. In this study, we have developed an upgraded version, i.e. KGS2, by employing 3D protein-ligand interaction fingerprints in reference selection. KGS2 was evaluated in combination with four scoring functions (X-Score, ChemPLP, ASP, and GoldScore) on five drug targets (HIV-1 protease, carbonic anhydrase 2, beta-secretase 1, beta-trypsin, and checkpoint kinase 1). In the in situ scoring test, considerable improvements were observed in most cases after application of KGS2. Besides, the performance of KGS2 was always better than KGS in all cases. In the more challenging molecular docking test, application of KGS2 also led to improved structure-activity relationship in some cases. KGS2 can be applied as a convenient "add-on" to current scoring functions without the need to re-engineer them, and its application is not limited to certain target proteins as customized scoring functions. As an interpolation method, its accuracy in principle can be improved further with the increasing knowledge of protein-ligand complex structures and binding affinity data. We expect that KGS2 will become a practical tool for enhancing the performance of current scoring functions in binding affinity prediction. The KGS2 software is available upon contacting the authors.


Hyperkalemia in both surgically and medically treated patients with primary aldosteronism.
Hyperkalemia is an important complication of adrenalectomy for patients with primary aldosteronism (PA). The frequency of hyperkalemia after medication using mineralocorticoid receptor antagonists (MRAs) for PA is unclear. The aim of this study is to investigate the frequency and the risk factors of hyperkalemia after surgery and medication for PA. The data of 376 patients with PA registered in a multicentre-collaborative study in Japan, including surgically treated patients (group A; n=142) and medically treated patients with MRAs (group B; n=234) were studied. The prevalence of hyperkalemic patients (serum potassium >5.0 mEq l-1) after treatment was higher in group A than group B (9.9 vs 3.8%, P<0.01). At diagnosis, the hyperkalemic patients were older and had a poorer renal function than the non-hyperkalemic patients in both groups (P<0.05). The hyperkalemic patients had severer PA in group A and milder PA in group B. The independent risk factor by a logistic regression analysis was only age in both groups. After treatment, the percentages of patients withdrawing antihypertensive drugs and the normalization of aldosterone renin ratio were not different between hyperkalemic and non-hyperkalemic patients in group A. The type and dose of MRAs and the combination of other antihypertensive drugs were not different between hyperkalemic and non-hyperkalemic patients in group B. In conclusion, the potential occurrence of hyperkalemia should be considered after medical as well as surgical treatment for PA, especially in patients with older age (>60 years) and impaired renal function (estimated glomerular filtration rate <70 ml min-1 per 1.73 m2) at diagnosis.


Neonatal pancytopenia associated with de novo 1q43-44 deletion and 10p15 duplication.
Deletion of 1q43-44 has been reported in >50 cases. Phenotype-genotype correlation of this deletion has recently been described based on 20 pure cases. This led to the definition of critical regions and candidate genes for microcephaly, corpus callosum abnormalities, and seizure disorders. Variable penetrance and expressivity are associated with 1q43-44 microdeletion syndrome, explaining the lack of correlation in rare cases. Despite variation in size of the deletion, most cases are characterized by typical dysmorphic features, but none have demonstrated neonatal pancytopenia. We report on a newborn with partial monosomy 1q43-44 and partial trisomy 10p15.1→10pter born with dysmorphic features and neonatal pancytopenia. Array-CGH analysis characterizes the deletion and the duplication as terminal with estimated sizes of 8 to 9 and 5 to 6 Mb, respectively. Conventional cytogenetic analysis showed the 10p duplication as unbalanced and translocated onto 1q. The deletion in the 1q43-44 region is the largest among the 20 cases reported most recently. The 10p partnership with the derivative 1q43-44 region is unique. We discuss the association of neonatal pancytopenia with 1q deletion and 10p duplication, in light of a recent published case of acute lymphoblastic leukemia in a constitutional case of 1q deletion and 1p duplication.


The Influence of Social and Nonsocial Variables on the Simon Effect.
Recently, the Simon effect (SE) has been observed in social contexts when two individuals share a two-choice task. This joint SE (JSE) has been interpreted as evidence that people co-represent their actions. However, it is still not clear if the JSE is driven by social factors or low-level mechanisms. To address this question, we applied a common paradigm to a joint Simon task (Experiments 1 and 4), a standard Simon task (Experiment 2), and a go/no-go task (Experiment 3). The results showed that both the JSE and the SE were modulated by the repetition/non-repetition of task features. Moreover, the JSE was differently modulated by the gender composition of the two individuals involved in the shared task and by their interpersonal relationship. Taken together, our results do not support a pure social explanation of the JSE, nevertheless, they show the independent role of different social factors in modulating the effect.


Molar distalization with 2K appliance: one-year follow-up.
Correction of class II molars in growing patients with acceptable facial profile can be performed by distalization of maxillary first molars. However, in patients where compliance is difficult intraoral means of molar distalization is required. This case report describes the use and effectiveness of a novel 2K appliance in an 11-year-old female having an orthognathic profile, skeletal Class I relation, and Angle's Class II division 1 malocclusion with crowding of 8 mm and 3 mm in the maxillary and mandibular arches, respectively. Nonextraction treatment was planned with bilateral distalization of the maxillary first molars. The amount of distalization achieved by 2K appliance was 3.5 mm with only 1° distal tipping. The 2K appliance required minimal patient cooperation, produced bodily movement of molars with minimal tipping/rotation, and prevented anchorage loss of the anterior teeth. This 2K molar distalization appliance was found to be an effective technique to control molars in all three planes of space.


Extensive variation in germline de novo mutations in Poecilia reticulata.
The rate of germline mutation is fundamental to evolutionary processes, as it generates the variation upon which selection acts. The guppy, Poecilia reticulata, is a model of rapid adaptation, however the relative contribution of standing genetic variation versus de novo mutation (DNM) to evolution in this species remains unclear. Here, we use pedigree-based approaches to quantify and characterize germline DNMs in three large guppy families. Our results suggest germline mutation rate in the guppy varies substantially across individuals and families. Most DNMs are shared across multiple siblings, suggesting they arose during early embryonic development. DNMs are randomly distributed throughout the genome, and male-biased mutation rate is low, as would be expected from the short guppy generation time. Overall, our study shows remarkable variation in germline mutation rate and provides insights into rapid evolution of guppies.


Psychophysiological Monitorization in a Special Operation Selection Course.
The present research aimed: i. to analyse the psychophysiological response of soldiers undertaking a special operation selection course; ii. to study the relationship between fat and muscle loss and the psychophysiological response of soldiers undertaking a special operation selection course. We analysed 46 professional soldiers from a special operations unit (25.1 ± 5.0 years, 1.8 ± 0.1 cm, 76.8 ± 7.9 kg, 24.4 ± 2.5 kg/m2) undertaking the last phase of their 10 weeks special operation selection course. Before and immediately after the exercise the following variables were assessed: Stress subjective perception, fatigue subjective perception, rating of perceived perception, cortical arousal, body temperature, blood oxygen saturation, spirometry, isometric hand strength, lower body muscular strength, urine, body composition, life engagement test, coping flexibility scale, acceptance and action questionnaire, perceived stress scale, anxiety state, visual analogue scale and differential aptitude test. A special operation selection course induced an intense stress and physical response as suggested by the psychophysiological changes with a significant (p < 0.05) increase in fatigue and stress subjective perception, blood oxygen saturation, Ph, cognitive impairment and motivation-loss. Moreover, decreased leg strength, peak expiratory flow, cortical arousal, body composition, body weight, fat and muscle mass, anxiety stress, alertness, sadness and tension decreased after the exercise. Regarding body composition, higher muscle mass loss participants were related to a higher cognitive impairment and similar psychophysiological response than lower fat mass loss participants.


Constructing Multifunctional Metallic Ni Interface Layers in the g-C3N4 Nanosheets/Amorphous NiS Heterojunctions for Efficient Photocatalytic H2 Generation.
The construction of exceptionally robust and high-quality semiconductor-cocatalyst heterojunctions remains a grand challenge toward highly efficient and durable solar-to-fuel conversion. Herein, novel graphitic carbon nitride (g-C3N4) nanosheets decorated with multifunctional metallic Ni interface layers and amorphous NiS cocatalysts were fabricated via a facile three-step process: the loading of Ni(OH)2 nanosheets, high-temperature H2 reduction, and further deposition of amorphous NiS nanosheets. The results demonstrated that both robust metallic Ni interface layers and amorphous NiS can be utilized as electron cocatalysts to markedly boost the visible-light H2 evolution over g-C3N4 semiconductor. The optimized g-C3N4-based photocatalyst containing 0.5 wt % Ni and 1.0 wt % NiS presented the highest hydrogen evolution of 515 μmol g-1 h-1, which was about 2.8 and 4.6 times as much as those obtained on binary g-C3N4-1.0%NiS and g-C3N4-0.5%Ni, respectively. Apparently, the metallic Ni interface layers play multifunctional roles in enhancing the visible-light H2 evolution, which could first collect the photogenerated electrons from g-C3N4, and then accelerate the surface H2-evolution reaction kinetics over amorphous NiS cocatalysts. More interestingly, the synergetic effects of metallic Ni and amorphous NiS dual-layer electron cocatalysts could also improve the TEOA-oxidation capacity through upshifting the VB levels of g-C3N4. Comparatively speaking, the multifunctional metallic Ni layers are dominantly favorable for separating and transferring photoexcited charge carriers from g-C3N4 to amorphous NiS cocatalysts owing to the formation of Schottky junctions, whereas the amorphous NiS nanosheets are mainly advantageous for decreasing the thermodynamic overpotentials for surface H2-evolution reactions. It is hoped that the implantation of multifunctional metallic interface layers can provide a versatile approach to enhance the photocatalytic H2 generation over different semiconductor-cocatalyst heterojunctions.


[Recent advances in retinoids studies].
Retinoids are defined as the compounds which elicit the specific biological responses through binding or activating the specific receptor(s). Retinoids modulate the cellular differentiation and proliferation in many types of cells. A series of retinoidal benzoic acids, named retinobenzoic acids, have potent activities on human promyelocytic leukemia cells, HL-60, and other assay systems. Among them, Am80, AM580 and Ch55 are more active than retinoic acid in most cases. As these compounds possess quite different structures or physicochemical properties from retinoic acid or conventional retinoids, they are expected to be applied clinically for the treatments of the diseases in oncology and dermatology. Recently, progresses on the mechanistic studies on retinoidal actions have been reported. One of them is isolation and cloning of human retinoic acid-receptors and the mechanism of retinoidal action was concluded that the retinoid-receptor complex interact directly with DNA to regulate the expression of the gene, like steroid hormone. The other is the establishment of the presence of the retinoid-specific-binding protein (RSBP) by the use of our retinobenzoic acids as the probe.


A family study of bipolar II disorder.
Professional raters who were blind to proband diagnosis used the schedule for affective disorders and schizophrenia (SADS-L) and the Research Diagnostic Criteria (RDC) to evaluate 1,210 first-degree relatives of 327 probands with primary major depression, participating in the family sub-study of the NIMH Collaborative Study of the Affective Disorders--Clinical Branch. Bipolar II probands were significantly more likely to have bipolar II relatives than were non-bipolar or bipolar I probands. Bipolar II probands were slightly more likely than non-bipolar probands and slightly less likely than bipolar I probands to have relatives with bipolar I illness. Similar patterns have emerged in two other recently reported family studies of bipolar II illness. Taken together, these data suggest heterogeneity among patients with bipolar II depression. Some appear to be genotypes for bipolar I illness, while a small proportion may be genotypes for non-bipolar illness. A third group, of undetermined size, may breed true.


WB1106, a novel nitric oxide-releasing derivative of telmisartan, inhibits hypertension and improves glucose metabolism in rats.
Angiotensin converting enzyme (ACE) inhibitors usually cause severe coughing and intolerance while antagonists for angiotensin AT(1) receptor do not stimulate the production of nitric oxide (NO). NO has been shown to regulate arterial hypertension and insulin resistance. Hence, new hybrids of antagonist for angiotensin AT(1) receptor and a NO donor may have potent anti-hypertensive effect and regulate glucose metabolism and insulin resistance. Herein, the effects of [6-(nitrooxymethyl)pyridin-2-yl] methyl 4'-[1-(1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzo[d]imidazol-3'-yl)ethyl] biphenyl-2-carboxylate (WB1106), a novel NO-releasing derivative of telmisartan newly synthesized, on the vasocontraction, hypertension and diet-induced insulin resistance were examined in vitro using rat aortic strips and in normotensive and spontaneous hypertension rats (SHR rats). Apparently, WB1106 induced the vasorelaxation of contracted rat aortic strips in a dose- and time-dependent manner, which depended on the activity of guanylate cyclase, a characteristic of NO-related function. Furthermore, WB1106 reduced the contractile and blood pressure responses to angiotensin II, which relied on the release of telmisartan. Moreover, treatment with WB1106 significantly reduced the blood pressure with similar potency to telmitarsan and increased the contents of cGMP in SHR rats. Therefore, WB1106 possesses both the angiotensin AT(1) receptor antagonist activity of telmisartan and the NO-releasing property of a 'slow NO donor'. Importantly, in contrast to equimolar telmisartan, treatment with WB1106 significantly attenuated body weight gains and improved glucose tolerance in high-fat and carbohydrate-fed rats, reflecting a synergistic effect of NO and telmisartan. Potentially, WB1106 may be a potent anti-hypertensive drug for treatment of hypertension and diabetes-related cardiovascular diseases in the clinic.


Advances in Drug Delivery and Biomaterials: Facts and Vision.
Drug delivery and biomaterials are different fields of science but, at the same time, are tightly related and intertwined. The 2018 CRS Italy Chapter Annual Workshop aims to explore recent advances in design and development in these areas. Many colleagues from Europe participated to the Workshop, stimulating the discussion. To foster the discussion on recent research and networking opportunities, especially among younger attendees, all poster-presenting authors were asked to provide a short talk. The very friendly and stimulating atmosphere allowed the attendees to explore new frontiers and tackle new horizons.


[Research on network pharmacology of alkaloids in Sophora alopecuroides].
It was aimed at exploring the potential pharmacological effects of alkaloids in Sophora alopecuroides by means of network pharmacology in this study. The main alkaloids in S. alopecuroides were collected for analysis of drug properties, prediction of potential targets and screening of signaling pathways. DAVID analysis tool combined with KEGG database was used to annotate and analyze the signaling pathway. The alkaloids-targets-signaling pathways network was built through Cytoscape software. Results showed that 17 alkaloids in S. alopecuroides involved 49 targets (170 times in all) and 22 important signaling pathways. Three nodes in model of network pharmacology were cross-linked, and the metabolic pathways were coordinated and regulated by each other. It indicated that alkaloids in S. alopecuroides may have therapeutic effect on diseases of cancer, metabolic disorder, endocrine system, digestive system, nervous system and so on.


Improving the Carrier Lifetime of Tin Sulfide via Prediction and Mitigation of Harmful Point Defects.
Tin monosulfide (SnS) is an emerging thin-film absorber material for photovoltaics. An outstanding challenge is to improve carrier lifetimes to >1 ns, which should enable >10% device efficiencies. However, reported results to date have only demonstrated lifetimes at or below 100 ps. In this study, we employ defect modeling to identify the sulfur vacancy and defects from Fe, Co, and Mo as most recombination-active. We attempt to minimize these defects in crystalline samples through high-purity, sulfur-rich growth and experimentally improve lifetimes to >3 ns, thus achieving our 1 ns goal. This framework may prove effective for unlocking the lifetime potential in other emerging thin-film materials by rapidly identifying and mitigating lifetime-limiting point defects.