Metabolic and monetary costs of avoidable parenteral nutrition use.
We prospectively collected data on in patients receiving parenteral nutrition to determine the magnitude of potentially preventable metabolic and monetary costs associated with parenteral nutrition. Parenteral nutrition was prescribed by the treating physicians with optional consultation from a multidisciplinary metabolic support service. Days on parenteral nutrition, appropriateness of parenteral nutrition, metabolic complications, and avoidable parenteral nutrition charges were determined. Parenteral nutrition use was considered "indicated" or "not indicated" based on the American Society for Parenteral and Enteral Nutrition guidelines and "preventable" if the gastrointestinal tract was functional but not accessed when possible. Of the 209 parenteral nutrition starts, 62% were indicated, 23% were preventable, and 15% were not indicated. Parenteral nutrition starts were deemed indicated in 82% of instances in which a metabolic support service consult was obtained, compared with 56% in which a consultation was not obtained (p = .004). Hyperglycemia was the most common metabolic complication, with an overall incidence of 20%. Metabolic complications occurred less frequently in patients who received a metabolic support service consultation compared with patients who did not (34% vs 66% of parenteral nutrition days, respectively; p = .004). Parenteral nutrition use of < or =5 days duration was significantly less frequent among patients who received metabolic support service consultation (16% vs 35%; p = .002). Parenteral nutrition that was not indicated or preventable resulted in excess annualized patient charges of more than one half million dollars not accounting for charges related to treatment of potentially avoidable parenteral nutrition complications. This study illustrates that not-indicated and preventable parenteral nutrition initiation, short-term parenteral nutrition use, and metabolic complications are less likely when patients receive consultation by a multidisciplinary team with expertise in nutrition and metabolic support. Furthermore, the avoidance of inappropriate parenteral nutrition use translates into substantial cost savings.


Whole-Exome Sequencing of Salivary Gland Mucoepidermoid Carcinoma.
Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. To explore the genetic origins of MEC, we performed systematic genomic analyses of these tumors. Whole-exome sequencing and gene copy-number analyses were performed for 18 primary cancers with matched normal tissue. FISH was used to determine the presence or absence of the MECT1-MAML2 translocation in 17 tumors. TP53 was the most commonly mutated gene in MEC (28%), and mutations were found only in intermediate- and high-grade tumors. Tumors with TP53 mutations had more mutations overall than tumors without TP53 mutations (P = 0.006). POU6F2 was the second most frequently mutated gene, found in three low-grade MECs with the same in-frame deletion. Somatic alterations in IRAK1, MAP3K9, ITGAL, ERBB4, OTOGL, KMT2C, and OBSCN were identified in at least two of the 18 tumors sequenced. FISH analysis confirmed the presence of the MECT1-MAML2 translocation in 15 of 17 tumors (88%). Through these integrated genomic analyses, MECT1-MAML2 translocation and somatic TP53 and POU6F2 mutations appear to be the main drivers of MEC. Clin Cancer Res; 23(1); 283-8. ©2016 AACR.


Linking Narcissism, Motivation, and Doping Attitudes in Sport: A Multilevel Investigation Involving Coaches and Athletes.
Research on coaching (Bartholomew, Ntoumanis, & Thøgersen-Ntoumani, 2009) has shown that coaches can display controlling behaviors that have detrimental effects on athletes' basic psychological needs and quality of sport experiences. The current study extends this literature by considering coach narcissism as a potential antecedent of coaches' controlling behaviors. Further, the study tests a model linking coaches' (n = 59) own reports of narcissistic tendencies with athletes' (n = 493) perceptions of coach controlling behaviors, experiences of need frustration, and attitudes toward doping. Multilevel path analysis revealed that coach narcissism was directly and positively associated with athletes' perceptions of controlling behaviors and was indirectly and positively associated with athletes' reports of needs frustration. In addition, athletes' perceptions of coach behaviors were positively associated-directly and indirectly-with attitudes toward doping. The findings advance understanding of controlling coach behaviors, their potential antecedents, and their associations with athletes' attitudes toward doping.


A Combination Treatment Using Ethyl Formate and Phosphine to Control Planococcus citri (Hemiptera: Pseudococcidae) on Pineapples.
Citrus mealybug, Planococcus citri (Risso), is a known quarantine pest that is difficult to control with phosphine (PH3) or low concentrations of ethyl formate (EF), particularly at low temperatures. Methyl bromide (MB) is a fumigant used for quarantine and preshipment (QPS) that can eradicate target pests with short fumigation periods. However, MB, which is an ozone-depleting substance, is scheduled to be phased out in South Korea over the next decade. There is no ideal alternative fumigant to replace MB for QPS of perishable commodities. A laboratory study was conducted to compare the individual effects of EF and PH3 individually, and the effects of EF mixed with PH3 as an MB alternative for the control of P. citri adults, nymphs, and eggs. In comparison to treatments with EF and PH3 individually, EF mixed with PH3 resulted in high toxicity to all stages of P. citri. The eggs were more tolerant than the nymphs and adults. A mixed treatment of EF and PH3 achieved complete control of eggs infesting pineapples at concentrations of 25.1/1.0 (EF/PH3) mg/liter at 8 °C for 4 h of exposures. This new combined EF/PH3 fumigation technology could offer shorter exposure times and less damage to perishable commodities at low temperatures, and could potentially be extended to controlling other quarantine pests as a replacement treatment for fruit and vegetables in which methyl bromide is currently being used.


Ceroid pigment formation and irreversible sterility in vitamin E deficiency.
Female rats maintained on a diet deficient in vitamin E for a prolonged period of 100 to 135 days, starting from birth, failed to conceive in spite of repeated matings. Dietary vitamin E supplementation for a period of 60 days following prolonged deficiency was ineffective in reversing the sterility, although a definite growth response was observed. These observations suggest that the tissue damage caused by lipid peroxidation, as evidenced by distinct brown ceroid pigment in the uterus and fallopian tubes, may be responsible for the irreversible loss of fertility observed in the vitamin E-deficient female rats.


"One and a half" minimally invasive transforaminal lumbar interbody fusion: single level transforaminal lumbar interbody fusion with adjacent segment unilateral laminotomy for bilateral decompression for spondylolisthesis with bisegmental stenosis.
Symptomatic lumbar spondylolisthesis is commonly accompanied by spinal stenosis in multiple segments. These pathologies are routinely treated by multilevel decompression and instrumented fusion. However, it was hypothesized that a minimally invasive surgery (MIS) fusion in the unstable segment combined with a unilateral laminotomy for bilateral decompression (ULBD) in the adjacent stenotic segment is a biomechanically feasible alternative to a two-level fusion and superior to open laminectomy adjacent to a fused segment. This concept has demonstrated success in a recently published biomechanical cadaver study performed by our group. The present article offers a detailed step by step technical description for an MIS-TLIF (transforaminal lumbar interbody fusion) with adjacent ULBD.


Birth defects in the sons and daughters of women who were exposed in utero to diethylstilbestrol (DES).
Prenatal exposure to diethylstilbestrol (DES) is associated with adverse health outcomes, including anatomic anomalies of the reproductive tract in women and of the genitourinary tract in men. The mouse model, which replicates many DES-related effects seen in humans, suggests that prenatal DES exposure causes alterations that may affect the next generation of offspring. We asked women participating in a large, multi-centre study of prenatal DES exposure to report birth defects occurring among 4029 sons and 3808 daughters (i.e., the third generation). A subcohort of 793 third generation daughters was also queried for birth defects. We used logistic regression models to generate odds ratio and 95% confidence intervals for the association between prenatal DES exposure in the mother and birth defects in the offspring. Based on the mothers' reports, overall birth defects were elevated in the sons (OR = 1.53; 95% CI = 1.04, 2.23) and in the daughters (OR = 2.35; 95% CI = 1.44, 3.82). Most estimates of association were imprecise, but daughters appeared to have an excess of heart conditions (OR = 4.56; 95% CI = 1.27, 16.34). Our data suggest a possible association between the mother's prenatal DES exposure and birth defects in their offspring, particularly in daughters. We cannot, however, rule-out the possible influence of reporting bias. In particular, the exposed daughters' elevated risk of cardiac defects may be as a result of the underreporting of these conditions by unexposed mothers.


Autologous Internal Limiting Membrane Fragment Transplantation for Large, Chronic, and Refractory Macular Holes.
To evaluate a technique of autologous internal limiting membrane (ILM) fragment transplantation for the treatment of large, chronic, and/or refractory macular holes (MH). This was a 6-month prospective interventional case series. Ten eyes of 10 patients with MH underwent pars plana vitretomy (PPV) and ILM peeling followed by transplantation of an autologous ILM fragment to the MH. Six patients had primary MH with an internal diameter greater than 500 µm and a duration of more than 18 months, including 1 patient with nonproliferative diabetic retinopathy previously treated with panretinal photocoagulation. Four eyes with MH had previously been submitted to PPV (i.e. 1 for retinal detachment and 3 to attempt to close large MH). One of the latter also displayed juxtapapillary choroidal neovascularization due to age-related macular degeneration. The primary and secondary outcomes were MH closure and improvement of the best corrected visual acuity (BCVA), respectively. Complete MH closure was achieved in all cases. A statistically significant improvement in the average BCVA was observed after 6 months of follow-up (p = 0.018; paired t test). The BCVA improved in 8 eyes (80%), and in 6 of those eyes it improved by ≥ 15 letters. In 1 patient, the BCVA remained unchanged after the surgery, but the visual field reportedly improved. One patient experienced a slight worsening (0.16 logMAR). Two cases developed atrophy of the retinal pigment epithelium despite MH closure and BCVA improvement. Treatment with autologous ILM fragment transplantation seems to be an efficient alternative for large, chronic, and refractory MH.


Escalated Aggression in Animal Models: Shedding New Light on Mesocorticolimbic Circuits.
Recent developments promise to significantly advance the understudied behavioral and neurobiology of aggression: (1) Animal models that capture essential features of human violence and callousness have been developed. These models range from mice that have been selectively bred for short attack latencies, monogamous prairie voles, and glucocorticoid-compromised rats to rodents and non-human primates that escalate their aggression after consuming or when withdrawing from alcohol. (2) Optogenetic stimulation and viral vector-based approaches have begun to identify overlapping and distinctive neural microcircuits and intracellular molecules for adaptive vs. excessive, maladaptive aggressive behavior in several rodent models. Projections from hypothalamic and mesencephalic neurons to the medial prefrontal cortex contain microcircuits that appear pivotal for the escalation of aggression.


Childhood trauma, alexithymia, and mental states recognition among individuals with alcohol use disorder and healthy controls.
Although prior work indicates a link between childhood trauma, alexithymia, and mental states recognition, empirical support is limited. Moreover, findings based on adult samples are mixed. Previous studies demonstrate that childhood trauma might either enhance, preserve, or reduce mental states recognition in selected at-risk populations. The current study investigates whether alcohol use disorder (AUD) status moderates the association between childhood trauma, alexithymia, and mental states recognition in a treatment-seeking AUD sample and non-AUD healthy adults. Data comes from 255 individuals participating in an ongoing project that compares emotional and behavioral functioning of patients treated in an inpatient setting for AUD and a comparison sample of 172 healthy controls (HCs). Mental states recognition was measured using a computerized version of the Reading the Mind in the Eyes Task (RMET). The presence of childhood trauma was assessed with the Childhood Trauma Questionnaire. Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). Demographic information, as well as alcohol drinking and psychopathological symptoms were assessed. A moderated mediation model was estimated whereby alexithymia was included as a mediator in the association between childhood trauma and RMET performance, with AUD diagnosis status moderating the link between alexithymia and RMET performance. Findings provide support for moderated mediation. Childhood emotional trauma impacted negative mental states recognition performance via difficulty describing feelings, but only among HCs (p < 0.01). Findings highlight the impact that AUD status has on the association between early life emotional trauma and difficulty describing feelings on individual differences in mental states recognition.


Abrogating Cbl-b in effector CD8(+) T cells improves the efficacy of adoptive therapy of leukemia in mice.
The clinical use of adoptive immunotherapy with tumor-reactive T cells to treat established cancers is limited in part by the poor in vivo survival and function of the transferred T cells. Although administration of exogenous cytokines such as IL-2 can promote T cell survival, such strategies have many nonspecific activities and are often associated with toxicity. We show here that abrogating expression of Casitas B-lineage lymphoma b (Cbl-b), a negative regulator of lymphocyte activation, in tumor-reactive CD8(+) T cells expanded ex vivo increased the efficacy of adoptive immunotherapy of disseminated leukemia in mice. Mechanistically, Cbl-b abrogation bypassed the requirement for exogenous IL-2 administration for tumor eradication in vivo. In addition, CD8(+) T cells lacking Cbl-b demonstrated a lower threshold for activation, better survival following target recognition and stimulation, and enhanced proliferative responses as a result of both IL-2-dependent and -independent pathways. Importantly, siRNA knockdown of Cbl-b in human CD8(+)CD28- effector T cell clones similarly restored IL-2 production and proliferation following target recognition independent of exogenous IL-2, enhanced IFN-γ production, and increased target avidity. Thus, abrogating Cbl-b expression in effector T cells may improve the efficacy of adoptive therapy of some human malignancies.


Electron small polarons and bipolarons in LiNbO(3).
An overview of the properties of electron small polarons and bipolarons is given, which can occur in the congruently melting composition of LiNbO(3) (LN). Such polarons influence the performance of this important optical material decisively. Since coupling to the lattice strongly quenches the tunnelling of free small polarons in general, they are easily localized at one site even by weak irregularities of a crystal. The mechanism of their optical absorptions is thus shared with those of small polarons localized by binding to selected defects. It is shown that the optical properties of free electrons in LN as well as those bound to Nb(Li) antisite defects can be attributed consistently to small polarons. This is extended to electron pairs forming bipolarons bound to Nb(Li)-Nb(Nb) nearest neighbours in the LN ground state. On the basis of an elementary phenomenological approach, relying on familiar concepts of defect physics, the peak energies, lineshapes, widths of the related optical absorption bands as well as the defect binding energies induced by lattice distortion are analysed. A criterion universally identifying small polaron absorption bands in oxide materials is pointed out. For the bipolarons, the dissociation energy, 0.27 eV, derived from a corresponding study of the mass action behaviour, is shown to be consistent with the data on isolated polarons. Based on experience with simple O(-) hole small polaron systems, a mechanism is proposed which explains why the observed small polaron optical absorptions are higher above the peak energies of the bands than those predicted by the conventional theory. The parameters characterizing the optical absorptions are seen to be fully consistent with those determining the electrical conductivity, i.e. the bipolaron dissociation energy and the positions of the defect levels as well as the activation energy of mobility. A reinterpretation of previous thermopower data of reduced LN on the basis of the bipolaron model confirms that the mobility of the free polarons is activated by 0.27 eV. On the basis of the level scheme of the bipolarons as well as the bound and free polarons the temperature dependence of the electronic conductivity is explained. The polaron/bipolaron concept also allows us to account for the concentrations of the various polaron species under the combined influence of illumination and heating. The decay of free and bound polarons dissociated from bipolarons by intense short laser pulses of 532 nm light is put in the present context. A critical review of alternative models, being proposed to explain the mentioned absorption features, is given. These proposals include: single free polarons in the (diamagnetic) LN ground state, oxygen vacancies in their various conceivable charge states, quadpolarons, etc. It is shown why these models cannot explain the experimental findings consistently.


Effects of Pictorial Warning Labels for Cigarettes and Quit-Efficacy on Emotional Responses, Smoking Satisfaction, and Cigarette Consumption.
Experimental research on pictorial warning labels for cigarettes has primarily examined immediate intentions to quit. Here, we present the results of a clinical trial testing the impact on smoking during and after a 28-day period of naturalistic exposure to pictorial versus text-only warnings. Daily cigarette smokers (N = 244) at two sites in the USA were randomly assigned to receive their regular brand of cigarettes for 4 weeks with one of three warnings: (a) text-only, (b) pictures and text as proposed by FDA, or (c) the warnings proposed by FDA with additional text that elaborated on the risks of smoking. Analyses examined the effects of pictorial versus text-only warnings and self-efficacy for quitting on cigarette consumption during and 1 month after the trial as mediated by emotional and cognitive responses as well as satisfaction with smoking. Stronger emotional responses to pictorial than text-only warnings predicted reduced satisfaction with smoking during the trial and lower cigarette consumption at follow-up among the majority of smokers who continued to smoke. Consistent with the efficacy-desire model, those with moderate efficacy reported the greatest reduction in consumption at follow-up. However, a small proportion of smokers (7%) who reported 7-day abstinence at follow-up did not exhibit a significant relation with self-efficacy. Pictorial warning labels proposed by FDA create unfavorable emotional reactions to smoking that predict reduced cigarette use compared to text alone, with even smokers low in self-efficacy exhibiting some reduction. Predictions that low self-efficacy smokers will respond unfavorably to warnings were not supported.


The effect of cortical lesions on the electromyographic response to joint displacement in the squirrel monkey forelimb.
The extent of participation of supraspinal structures in the generation of the long latency (M2) electromyographic (EMG) response to imposed joint displacement may be reflected in the effect of lesions of the central nervous system. M2 activity has been reported in a variety of studies to be either present or absent following supraspinal lesions. Since other studies have shown different characteristics of long latency activity in proximal as compared to distal upper limb muscles in primates, the present experiments were conducted to determine the effect of motor cortical (area 4) lesions on reflex activity generated in a proximal versus a distal upper limb muscle. Chronic experiments were performed on squirrel monkeys with unilateral lesions of the forelimb motor cortex (area 4) which was mapped with the aid of electrical stimulation. Input-output relationships were determined between torque motor-imposed joint rotation and the EMG response in the stretched muscles (flexor digitorum profundus (FDP) and short head of biceps (SHB)). The EMG responses were reported as a percentage of maximum EMG output and controlled for base line EMG level. The "gain" (slope of EMG response versus torque load) for FDP M2 activity was markedly decreased in the limb contralateral to the area 4 lesion as compared to the opposite limb. This decrease was independent of base line EMG levels. In SHB, early latency (M1) EMG activity was significantly increased, but M2 activity appeared unaffected on the side contralateral to the lesion. The results demonstrate that the central and peripheral mechanisms generating M2 activity in FDP differ from those in SHB in terms of motor cortical dependency.


Amylose in starch: towards an understanding of biosynthesis, structure and function.
Starch granules are composed of two distinct glucose polymers - amylose and amylopectin. Amylose constitutes 5-35% of most natural starches and has a major influence over starch properties in foods. Its synthesis and storage occurs within the semicrystalline amylopectin matrix of starch granules, this poses a great challenge for biochemical and structural analyses. However, the last two decades have seen vast progress in understanding amylose synthesis, including new insights into the action of GRANULE BOUND STARCH SYNTHASE (GBSS), the major glucosyltransferase that synthesises amylose, and the discovery of PROTEIN TARGETING TO STARCH1 (PTST1) that targets GBSS to starch granules. Advances in analytical techniques have resolved the fine structure of amylose, raising new questions on how structure is determined during biosynthesis. Furthermore, the discovery of wild plants that do not produce amylose revives a long-standing question of why starch granules contain amylose, rather than amylopectin alone. Overall, these findings contribute towards a full understanding of amylose biosynthesis, structure and function that will be essential for future approaches to improve starch quality in crops.


The association between economic development, lifestyle differentiation, and C-reactive protein concentration within rural communities in Hainan Island, China.
Earlier fieldwork in rural areas of Hainan Island, China, demonstrated that during the course of economic development increasing differences had emerged in lifestyles within communities. It is possible that these variations might have stratified residents into subpopulations with different health attributes. This study examined the association between C-reactive protein (CRP) concentration, a biomarker of future cardiovascular events, and personal lifestyle parameters and the degree of community-level economic development among rural communities. A cross-sectional field survey was undertaken in 19 rural communities in Hainan. Convenience sampling was used to recruit 1,744 participants. Dried blood spot samples were collected to measure high-sensitivity CRP concentration. Sex-stratified multilevel regression analyses were conducted to identify factors associated with CRP concentration among the participants. While CRP concentration was negatively associated with being married and (more) education among men, for women CRP concentration was associated with the frequency of poultry consumption (P = 0.014) and the experience of migratory work in the previous year (P = 0.009). In addition, for females, living in communities with a greater degree of inequality, as indexed by the Gini coefficient, was also associated with increased CRP concentration (P = 0.003). Given that CRP concentration is a marker of future CVD risk, this study suggests that within these previously homogenous rural communities, economic development might have stratified people into population subgroups with a different CVD risk.


Prospective multicenter evaluation of the direct flow medical transcatheter aortic valve.
The study sought a prospective multicenter nonrandomized evaluation of the Direct Flow Medical (DFM) system for the treatment of severe aortic stenosis. The DFM transcatheter aortic valve system is a nonmetallic design with a pressurized support structure that allows precise positioning, retrieval, and assessment of valve performance prior to permanent implantation. One hundred high surgical risk patients with severe aortic stenosis were evaluated for the primary endpoint. There were 75 patients in the group evaluable for the secondary endpoints and 25 in the pre-specified roll-in training phase. Echocardiographic and angiographic data were evaluated by an independent core laboratory and adverse events adjudicated by clinical event committee and classified according to Valve Academic Research Consortium (VARC) criteria. There was 99% freedom from all cause mortality at 30 days (primary endpoint). VARC criteria defined 30 day combined freedom from patient safety event rate was 91% and overall device success was 93%. The post-implantation echocardiography results demonstrated mild or no aortic regurgitation in 99% (73 of 74) with a mean gradient of 12.6 ± 7.1 mm Hg (n = 72) and effective orifice area of 1.50 ± 0.56 cm(2) and New York Heart Association functional class was I or II in 92% of cases. The present study demonstrates the safety and efficacy of the DFM system in surgical high risk patients with severe aortic stenosis and complex anatomy aortic regurgitation was less than moderate in 99% of patients.


Altered turnover of polyphosphoinositides in the erythrocyte membrane of the spontaneously hypertensive rat.
The metabolism of inositol phospholipids of the erythrocyte membrane was compared in normotensive Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone SHR (SHR-SP) rats. This was performed on isolated ghost membranes by measuring the incorporation of 32P from [ gamma-32P ] adenosine triphosphate (ATP) into the diphosphoinositides (DPI) and the triphosphoinositides (TPI) which were the only 32P-labeled phospholipids. 32P-labeling of TPI was altered in adult and 3-week-old SHR as well as in SHR-SP compared to WKY controls; the radioactivity associated with TPI in hypertensive rats was about 30% lower than that associated with TPI in age-matched normotensive controls. By contrast, the radioactivity associated with DPI was similar in both hypertensive and normotensive rats. Measurement of the phosphoinositide distribution in both SHR and WKY indicates that the change observed in 32P-TPI could not be accounted for by a reduced phosphatidylinositol content in SHR membrane. Measurement of the Mg2+-activated TPI-phosphomonoesterase and of the Ca2+-activated polyphosphoinositide phosphodiesterase activities did not show any significant difference between SHR and WKY. It thus appears that the altered phosphoinositide metabolism observed in hypertensive rats was a consequence of some alteration in the activity of kinases which are responsible for the conversion of phosphatidylinositol into DPI and TPI. These results also suggest that the defect in phosphoinositide metabolism observed in genetically hypertensive rats was not a consequence of the blood pressure elevation and could be related to the pathogenesis of hypertension.


The Drosophila TNF Eiger Is an Adipokine that Acts on Insulin-Producing Cells to Mediate Nutrient Response.
Adaptation of organisms to ever-changing nutritional environments relies on sensor tissues and systemic signals. Identification of these signals would help understand the physiological crosstalk between organs contributing to growth and metabolic homeostasis. Here we show that Eiger, the Drosophila TNF-α, is a metabolic hormone that mediates nutrient response by remotely acting on insulin-producing cells (IPCs). In the condition of nutrient shortage, a metalloprotease of the TNF-α converting enzyme (TACE) family is active in fat body (adipose-like) cells, allowing the cleavage and release of adipose Eiger in the hemolymph. In the brain IPCs, Eiger activates its receptor Grindelwald, leading to JNK-dependent inhibition of insulin production. Therefore, we have identified a humoral connexion between the fat body and the brain insulin-producing cells relying on TNF-α that mediates adaptive response to nutrient deprivation.


Your infections are what you eat: How host ecology shapes the helminth parasite communities of lizards.
Understanding how parasite communities are assembled, and the factors that influence their richness, can improve our knowledge of parasite-host interactions and help to predict the spread of infectious diseases. Previous comparative analyses have found significant influences of host ecology and life history, but focused on a few select host taxa. Host diet and habitat use play key roles in the acquisition of parasitic helminths as many are trophically transmitted, making these attributes potentially key indicators of infection risk. Given the paucity of comparative studies with non-piscine, non-avian or non-mammalian hosts, it is critical to examine the degree to which host ecology influences parasite communities in other host taxa in order to identify common drivers. We examined helminth diversity in over 350 species of lizards in relation to their body mass, ecology (diet and habitat use) and life history (clutch size, and ovo- or viviparity) using previously published data. Overall, lizard species with herbivorous diets harboured fewer types of helminths (especially larval stages), with similar results for traits that were ultimately strongly associated with diet (host mass and habitat use). Large hosts tended to be herbivores with few helminth types, whereas species utilizing arboreal habitats typically consumed some animal matter and hosted more helminths. Understanding how host ecology and life history are related to their parasite assemblages has significant implications for the risk of acquiring novel parasites. Our results indicate an overwhelming influence of host diet such that many helminths may be relatively easily acquired by hosts in new ranges, or through dietary shifts.


Endocrine dysfunction in patients of leprosy.
Leprosy is a chronic granulomatous disease and affects many internal organs in addition to the skin and peripheral nerves. Endocrine dysfunction is often silent and is often missed in patients of leprosy leading to significant morbidity. We studied the presence of occult endocrine disorders in leprosy patients and compared the same with disease parameters. We evaluated 40 patients of leprosy (aged 18-70 years, any duration) in this cross-sectional, observational study. All subjects were assessed for pituitary, thyroid, adrenal, gonadal function, and dynamic testing was done when deemed necessary. The participants were divided into two groups: Group 1 (Leprosy, n = 40) and Group 2 (Controls, n = 20) and the data were analyzed with appropriate statistical tests. The study participants (35 males, 5 females) had a mean age of 36.4 ± 11.3 years, and duration of the disease was 2.5 ± 5.5 years. Eleven out of 40 patients showed results consistent with an endocrine disorder, including subclinical hypothyroidism (n = 4), sick euthyroid syndrome (n = 3), growth hormone (GH) deficiency (n = 2), primary hypogonadism (n = 2) and secondary hypogonadism in one patient. One patient had partial hypopituitarism (GH deficiency and secondary hypogonadism) and none of the controls showed any hormonal dysfunction. Testosterone levels showed inverse correlation with the number of skin patches (P = 0.0006). Occult endocrine dysfunction is seen in a quarter of patients with leprosy. Thyroid and gonadal axes abnormalities are common, and the severity is more in lepromatous forms of the disease. Further large studies are required to confirm the findings observed in our study.


[Effects and mechanism of berberine on the hypertensive renal injury rats induced by enriched high fat-salt-fructose diet].
To study the effects of berberine on hypertensive renal injury model in rats fed by enriched high fat-salt-fructose diet . hypertensive renal injury model was esteblished by feeding enriched high fat-salt-fructose diet for 8 weeks. On the basis of animal blood pressure, hypertensive rats were randomly divided into model group (10 rats, distilled water), captopril group (10 rats,25 mg/kg), berberine high dose group (10 rats, 300 mg/kg) and low dose group (10 rats, 100 mg/kg). These rats were fed by enriched high fat-salt-fructose diet and treated by intragastric administration with drugs for 4 weeks. And normal control group (10 rats) was set Blood pressure was determined at 0, 4, 8, 10, 12 weekend,and after 4 weeks of drugs treatment, getting urine to determine urine protein, taking blood serum to determine blood urea nitrogen, serum creatinine,GHb,MDA and activity of SOD. The content of H2O2 and GSH-Px and activity of CAT in kidney tissues were determined also. Compared with normal control group, blood pressure, urine protein, blood urea nitrogen, serum creatinine and MDA and GHb in serum of model rats obviously increased (P < 0.01), the activity of SOD decreased (P < 0.01), higher content of H2O2 and lower content of GSH-Px and activity of CAT (P < 0.01) in the kidney tissues. Treated with berberine for 4 weeks, elevated blood pressure and heightened levels of urine protein, blood urea nitrogen and serum creatinine in model rats were depressed significantly (P < 0.01), and elevated the activity of SOD, lowed the levels of MDA and GHb in blood serum (P < 0.01). At the same time, berberine increased the activities of GSH-Px and CAT (P < 0.01) and slightly lowed the content of H2O2 in the kidney tissues. Berberine has protecting effects on the hypertensive renal impairment model rats fed by enriched high fat-salt-fructose diet, which are concerned with elevated antioxidant capability in body and kidney tissues.


Multiplexed analysis of glycan variation on native proteins captured by antibody microarrays.
Carbohydrate post-translational modifications on proteins are important determinants of protein function in both normal and disease biology. We have developed a method to allow the efficient, multiplexed study of glycans on individual proteins from complex mixtures, using antibody microarray capture of multiple proteins followed by detection with lectins or glycan-binding antibodies. Chemical derivatization of the glycans on the spotted antibodies prevented lectin binding to those glycans. Multiple lectins could be used as detection probes, each targeting different glycan groups, to build up lectin binding profiles of captured proteins. By profiling both protein and glycan variation in multiple samples using parallel sandwich and glycan-detection assays, we found cancer-associated glycan alteration on the proteins MUC1 and CEA in the serum of pancreatic cancer patients. Antibody arrays for glycan detection are highly effective for profiling variation in specific glycans on multiple proteins and should be useful in diverse areas of glycobiology research.


Synthesis of phenanthridine spiropyrans and studies of their effects on G-quadruplex DNA.
G-quadruplex (G4) DNA structures are involved in many important biological processes and can be linked to several human diseases. Drug-like low molecular weight compounds that target G4 structures are therefore interesting not only for their potential therapeutic properties but also for their potential use as chemical research tools. We report here on the development of methods to synthesize spiropyrans using a condensation-cyclisation reaction of quaternary salts of α-methyl quinoline or phenanthridine with salicylaldehydes. Evaluation of the synthesized phenanthridine spiropyrans' interactions with G4 DNA was performed with a Thioflavin T displacement assay, circular dichroism, Taq DNA polymerase stop assay, and NMR. This revealed that the substitution pattern on the phenanthridine spiropyrans was very important for their ability to bind and stabilize G4 structures. Some of the synthesized low molecular weight spirocyclic compounds efficiently stabilized G4 structures without inducing structural changes by binding the first G-tetrad in the G4 structure.


Using topography to meet wildlife and fuels treatment objectives in fire-suppressed landscapes.
Past forest management practices, fire suppression, and climate change are increasing the need to actively manage California Sierra Nevada forests for multiple environmental amenities. Here we present a relatively low-cost, repeatable method for spatially parsing the landscape to help the U.S. Forest Service manage for different forest and fuel conditions to meet multiple goals relating to sensitive species, fuels reduction, forest products, water, carbon storage, and ecosystem restoration. Using the Kings River area of the Sierra Nevada as a case study, we create areas of topographically-based units, Landscape Management Units (LMUs) using a three by three matrix (canyon, mid-slope, ridge-top and northerly, southerly, and neutral aspects). We describe their size, elevation, slope, aspect, and their difference in inherent wetness and solar radiation. We assess the predictive value and field applicability of LMUs by using existing data on stand conditions and two sensitive wildlife species. Stand conditions varied significantly between LMUs, with canyons consistently having the greatest stem and snag densities. Pacific fisher (Martes pennanti) activity points (from radio telemetry) and California spotted owl (Strix occidentalis occidentalis) nests, roosts, and sightings were both significantly different from uniform, with a disproportionate number of observations in canyons, and fewer than expected on ridge-tops. Given the distinct characteristics of the LMUs, these units provide a relatively simple but ecologically meaningful template for managers to spatially allocate forest treatments, thereby meeting multiple National Forest objectives. These LMUs provide a framework that can potentially be applied to other fire-dependent western forests with steep topographic relief.


The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly.
p27(BBP/eIF6) is an evolutionarily conserved protein that was originally identified as p27(BBP), an interactor of the cytoplasmic domain of integrin beta4 and, independently, as the putative translation initiation factor eIF6. To establish the in vivo function of p27(BBP/eIF6), its topographical distribution was investigated in mammalian cells and the effects of disrupting the corresponding gene was studied in the budding yeast, Saccharomyces cerevisiae. In epithelial cells containing beta4 integrin, p27(BBP/eIF6) is present in the cytoplasm and enriched at hemidesmosomes with a pattern similar to that of beta4 integrin. Surprisingly, in the absence and in the presence of the beta4 integrin subunit, p27(BBP/eIF6) is in the nucleolus and associated with the nuclear matrix. Deletion of the IIH S. cerevisiae gene, encoding the yeast p27(BBP/eIF6) homologue, is lethal, and depletion of the corresponding gene product is associated with a dramatic decrease of the level of free ribosomal 60S subunit. Furthermore, human p27(BBP/eIF6) can rescue the lethal effect of the iihDelta yeast mutation. The data obtained in vivo suggest an evolutionarily conserved function of p27(BBP/eIF6) in ribosome biogenesis or assembly rather than in translation. A further function related to the beta4 integrin subunit may have evolved specifically in higher eukaryotic cells.


[Validation of colorectal cancer diagnostic codes in a hospital administration data set].
To validate the ability of a hospital administration data set (minimum data set [MDS]) to detect incident cases of colorectal cancer using the Murcia Cancer Registry (MCR) as the gold standard and to measure agreement between the MDS and registration of colorectal cancer. A cross sectional validation study of the MDS of the main hospital in the region of Murcia (Spain) was conducted. The study population consisted of incident cases of colorectal cancer in 2000 obtained from the MCR and cases in the MDS of the above-mentioned hospital for the same year with an ICD-9 diagnostic code between 153.0 and 154.1, eliminating readmissions. During the process, two analyses were performed: one analysis with the principal diagnosis only and another with all the diagnostic codes. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and agreement was calculated with their 95% confidence intervals (CI). With the first diagnosis only, the MDS detected 80% of the incident cases of colorectal cancer with a PPV of 75%. With all the diagnoses, the MDS detected 85% of the cases with a PPV of 64%. The agreement in codification was high at three digits (kappa 88% [95% CI, 0.79-0.97] first diagnosis, 89% [95% CI, 0.80-0.97] all diagnoses) as well as at four digits (kappa 77% [IC, 0.68-0.85] first diagnosis, 78% [95% CI, 0.70-0.86] all diagnoses) in both analyses. Because of its high sensitivity, the MDS is a good source for detecting incident cases of cancer. The high agreement found in the site of colorectal cancer helps to consolidate the MDS as a data source for cancer registration.


Sex differences in the treatment and outcomes of patients hospitalized with ST-elevation myocardial infarction.
To compare mortality for women and men hospitalized with ST-elevation myocardial infarction (STEMI) by age and revascularization status. There is little information on the mortality of men and women not undergoing revascularization, and the impact of age on relative male-female mortality needs to be revisited. An observational database of 23,809 patients with STEMI presenting at nonfederal New York State hospitals between 2013 and 2015 was used to compare risk-adjusted inhospital/30-day mortality for women and men and to explore the impact of age on those differences. Women had significantly higher mortality than men overall (adjusted odds ratio [AOR] = 1.15, 95% CI [1.04, 1.28]), and among patients aged 65 and older. Women had lower revascularization rates in general (AOR = 0.64 [0.59, 0.69]) and for all age groups. Among revascularized STEMI patients, women overall (AOR = 1.30 [1.10, 1.53]) and over 65 had higher mortality than men. Among patients not revascularized, women between the ages of 45 and 64 had lower mortality (AOR = 0.68 [0.48, 0.97]). Women with STEMI, and especially older women, had higher inhospital/30-day mortality rates than their male counterparts. Women had higher mortality among revascularized patients, but not among patients who were not revascularized.


Interconnected PolymerS TeChnology (IPSTiC): An Effective Approach for the Modulation of 5α-Reductase Activity in Hair Loss Conditions.
Hair loss represents a condition that adversely affects the social life of patients. The most common cause is androgenetic alopecia (AGA), which is a genetically determined progressive hair-loss condition involving 5α-reductase. In this study, a novel anti-baldness agent based on Interconnected PolymerS TeChnology (IPSTiC), which is an effective strategy for the delivery of bioactive molecules, was developed. This product (IPSTiC patch hair) is based on a polymeric blend consisting of high molecular weight hyaluronic acid and soybean proteins and is able to improve efficacy and stability of bioactive ingredients such as Origanum vulgare leaf extract, Camellia Sinensis leaf extract, and Capsicum Annuum fruit extract. The efficacy of the developed anti-baldness agent was investigated by performing several tests including NO radical and 5α-reductase inhibition assays, stability studies under different conditions, and in vitro diffusion studies using Franz cells. The biocompatibility of IPSTiC patch hair was also evaluated by in vitro analysis of the pro-sensitising potential and EPISKIN model. The obtained results confirmed both the efficacy and safety of IPSTiC patch hair supporting the potential use of this product in the topical treatment of AGA.


Measuring natural phytoplankton fluorescence and biomass: a case study of algal bloom in the Pearl River estuary.
A moored optical buoy was deployed in the Pearl River estuarine waters for a 15-day period. A four-day algal bloom event occurred during this study period. Both chlorophyll a concentration and algal cell density (a proxy for biomass) changed dramatically before and after the event. The chlorophyll concentration at a 2.3m depth rose from 5.15 mg/m(-3) at 15:00 h on August 19 to 23.62 mg/m(-3) at 9:00 h on August 21, and then decreased to 3.24 mg/m(-3) at 15:00 h on August 24. The corresponding cell density ranged from 1.57 x 10(5) to 1.76 x 10(6)cells/L. We used normalized fluorescence line height (NFLH) and normalized fluorescence intensity (NFI) in order to determine fluorescence activity. Combined with the in situ sampling dataset, we were able to correlate natural fluorescence (NFLH and NFI) with chlorophyll a concentrations, and found correlation coefficients of 0.72 and 0.75, respectively. We also found correlations between natural fluorescence and cell density, with correlation coefficients of 0.71 and 0.65, respectively. These results indicate that applying continuous time series of natural fluorescence can reflect changes in biomass. This technique will prove extremely useful for in situ and real-time observations using an optical buoy. Although there are still problems to solve in the real-time observation of natural fluorescence in algal bloom events, we discuss the primary factors affecting fluorescence signals and suggest possible methods for mitigating these issues.


[(18)F]-Group 13 fluoride derivatives as radiotracers for positron emission tomography.
The field of (18)F chemistry is rapidly expanding because of the use of this radionuclide in radiotracers for positron emission tomography (PET). Until recently, most [(18)F]-radiotracers were generated by the direct attachment of (18)F to a carbon in the organic backbone of the radiotracer. The past decade has witnessed the emergence of a new strategy based on the formation of an (18)F-group 13 element bond. This approach, which is rooted in the field of fluoride anion complexation/coordination chemistry, has led to the development of a remarkable family of boron, aluminium and gallium [(18)F]-fluoride anion complexing agents which can be conjugated with peptides and small molecules to generate disease specific PET radiotracers. This review is dedicated to the chemistry of these group 13 [(18)F]-fluorides anion complexing agents and their use in PET. Some of the key fluoride-binding motifs covered in this review include the trifluoroborate unit bound to neutral or cationic electron deficient backbones, the BF2 unit of BODIPY dyes, and AlF or GaF3 units coordinated to multidentate Lewis basic ligands. In addition to describing how these moieties can be converted into their [(18)F]-analogs, this review also dicusses their incorporation into bioconjugates for application in PET.


A conserved proline triplet in Val-tRNA synthetase and the origin of elongation factor P.
Bacterial ribosomes stall on polyproline stretches and require the elongation factor P (EF-P) to relieve the arrest. Yet it remains unclear why evolution has favored the development of EF-P rather than selecting against the occurrence of polyproline stretches in proteins. We have discovered that only a single polyproline stretch is invariant across all domains of life, namely a proline triplet in ValS, the tRNA synthetase, that charges tRNA(Val) with valine. Here, we show that expression of ValS in vivo and in vitro requires EF-P and demonstrate that the proline triplet located in the active site of ValS is important for efficient charging of tRNA(Val) with valine and preventing formation of mischarged Thr-tRNA(Val) as well as efficient growth of E. coli in vivo. We suggest that the critical role of the proline triplet for ValS activity may explain why bacterial cells coevolved the EF-P rescue system.


Thermal contribution of compact bone to intervening tissue-like media exposed to planar ultrasound.
The presence of bone in the ultrasound beam path raises concerns, both in diagnostic and therapeutic applications, because significant temperature elevations may be induced at nearby soft tissue-bone interfaces due the facts that ultrasound is (i) highly absorbed in bone and (ii) reflected at soft tissue-bone interfaces in various degrees depending on angle of incidence. Consequently, in ultrasonic thermal therapy, the presence of bone in the ultrasound beam path is considered a major disadvantage and it is usually avoided. However, based on clinical experience and previous theoretical studies, we hypothesized that the presence of bone in superficial unfocused ultrasound hyperthermia can actually be exploited to induce more uniform and enhanced (with respect to the no-bone situation) temperature distributions in superficial target volumes. In particular, we hypothesize that the presence of underlying bone in superficial target volume enhances temperature elevation not only by additional direct power deposition from acoustic reflection, but also from thermal diffusion from the underlying bone. Here we report laboratory results that corroborate previous computational studies and strengthen the above-stated hypothesis. Three different temperature measurement techniques, namely, thermometric (using fibre-optic temperature probes), thermographic (using an infrared camera) and magnetic resonance imaging (using proton resonance frequency shifts), were used in high-power short-exposure, and in low-power extended-exposure, experiments using a 19 mm diameter planar transducer operating at 1.0 and 3.3 MHz (frequencies of clinical relevance). The measurements were performed on three technique-specific phantoms (with and without bone inclusions) and experimental set-ups that resembled possible superficial ultrasound hyperthermia clinical situations. Results from all three techniques were in general agreement and clearly showed that significantly higher heating rates (greater than fourfold) were induced in soft tissue-like phantom materials adjacent (within approximately 5 mm) to a bovine bone as compared to similar experiments without bone inclusions. For low-power long-exposure experiments, where thermal conduction effects are significant, the thermal impact of bone reached at distances > 10 mm from the bone surface (upstream of the bone). Therefore, we hypothesize that underlying bone exposed to planar ultrasound hyperthermia creates a high-temperature thermal boundary at depth that compensates for beam attenuation, thus producing more uniform temperature distribution in the intervening tissue layers. With appropriate technology, this finding may lead to improved thermal doses in superficial treatment sites such as the chest wall and the head/neck.


Differential diagnosis of Hispanic children referred for autism spectrum disorders: complex issues.
This study examines the decision-making process used for differential diagnosis of a sample of Hispanic children referred for autism spectrum disorders (ASDs). Of the sample of 28 children, 18 were diagnosed with ASDs. Of the 10 children who were not diagnosed with ASDs, 80% were found to have multiple diagnostic labels or comorbidities. Mann-Whitney U analyses determined the differences between the children with the most severe social impairment, children with less severe social impairment and the non-autistic children on several domains commonly used to assess ASDs. These analyses indicated significant differences in some characteristics of the children in the sample. Based on these results, a decision-tree for the diagnosis of children with and without ASDs with comorbid disorders was developed.


The impact of COVID-19 on the treatment of opioid use disorder in carceral facilities: a cross-sectional study.
While the COVID-19 pandemic disrupted healthcare delivery everywhere, persons with carceral system involvement and opioid use disorder (OUD) were disproportionately impacted and vulnerable to severe COVID-associated illness. Carceral settings and community treatment programs (CTPs) rapidly developed protocols to sustain healthcare delivery while reducing risk of COVID-19 transmission. This survey study assessed changes to OUD treatment, telemedicine use, and re-entry support services among carceral and CTPs participating in the National Institute on Drug Abuse (NIDA)-funded study, Long-Acting Buprenorphine vs. Naltrexone Opioid Treatments in Criminal Justice System-Involved Adults (EXIT-CJS) study. In December 2020, carceral sites (n = 6; median pre-COVID 2020 monthly census = 3468 people) and CTPs (n = 7; median pre-COVID 2020 monthly census = 550 patients) participating in EXIT-CJS completed a cross-sectional web-based survey. The survey assessed changes pre- (January-March 2020) and post- (April-September 2020) COVID-19 in OUD treatment, telemedicine use, re-entry supports and referral practices. Compared to January-March 2020, half of carceral sites (n = 3) increased the total number of persons initiating medication for opioid use disorder (MOUD) from April-September 2020, while a third (n = 2) decreased the number of persons initiated. Most CTPs (n = 4) reported a decrease in the number of new admissions from April-September 2020, with two programs stopping or pausing MOUD programs due to COVID-19. All carceral sites with pre-COVID telemedicine use (n = 5) increased or maintained telemedicine use, and all CTPs providing MOUD (n = 6) increased telemedicine use. While expansion of telemedicine services supported MOUD service delivery, the majority of sites experienced challenges providing community support post-release, including referrals to housing, employment, and transportation services. During the COVID-19 pandemic, this small sample of carceral and CTP sites innovated to continue delivery of treatment for OUD. Expansion of telemedicine services was critical to support MOUD service delivery. Despite these innovations, sites experienced challenges providing reintegration supports for persons in the community. Pre-COVID strategies for identifying and engaging individuals while incarcerated may be less effective since the pandemic. In addition to expanding research on the most effective telemedicine practices for carceral settings, research exploring strategies to expand housing and employment support during reintegration are critical.


Comparative effects of moxifloxacin and clarithromycin on the normal intestinal microflora.
Twelve healthy male subjects age range 24-40 y participated in the investigation. The trial was divided into 2 35-d periods. The 2 treatment regimens were: (i) 1 x 400 mg moxifloxacin tablet in the morning and 1 placebo tablet in the evening for 7 d; and (ii) 1 x 500 mg clarithromycin tablet in the morning and 1 x 500 mg clarithromycin tablet in the evening for 7 d. Each subject received firstly I treatment regimen and secondly the other treatment regimen. The wash-out period was 6 weeks between the two treatment regimens. Moxifloxacin caused significant decreases of enterococci and enterobacteria during the administration period while the numbers of staphylococci, streptococci, Bacillus and Candida were not affected. No impact on peptostreptococci, lactobacilli, Veillonella, Bacteroides or fusobacteria was observed, while bifidobacteria and clostridia decreased during moxifloxacin administration. The microflora was normalized after 35 d. Clarithromycin caused significant reduction of Escherichia coli while the numbers of enterococci, Enterobacter, Citrobacter, Klebsiella and Pseudomonas increased markedly. No significant changes in the numbers of staphylococci, streptococci, Bacillus and Candida were noticed. In the anaerobic microflora bifidobacteria, lactobacilli and clostridia were suppressed, while no changes in peptostreptococci, Veillonella, Bacteroides and fusobacteria were found. The microflora was normalized in all volunteers after 35 d.


Selection and Evaluation of Staphylococcus xylosus as a Biocontrol Agent against Toxigenic Moulds in a Dry-Cured Ham Model System.
Toxigenic moulds can develop on the surface of dry-cured meat products during ripening due to their ecological conditions, which constitutes a risk for consumers. A promising strategy to control this hazard is the use of antifungal microorganisms usually found in these foods. However, to date, the effectiveness of gram-positive catalase-positive cocci (GCC+) has not been explored. The aim of this work was to select GCC+ isolates with antifungal activity to study its effectiveness in a dry-cured ham model system at the environmental conditions reached during the ripening. Forty-five strains of GCC+ were evaluated and the isolate Staphylococcus xylosus Sx8 was selected to assess its efficacy at two different concentrations (106 and 104 cfu/mL) against Penicillium nordicum, Aspergillus flavus, Aspergillus parasiticus, and Penicillium griseofulvum at 15, 20, and 25 °C. The results showed that the inoculation of 106 cfu/mL of S. xylosus completely inhibited the growth of most fungi. In addition, in the presence of this strain at 104 cfu/mL, a significant reduction in fungal growth and mycotoxins production was observed at the three temperatures studied. In conclusion, S. xylosus Sx8 possesses great potential as a biological agent to control toxigenic moulds in dry-cured meat products.


Epithelial thickness and lipid droplets in the hepatopancreas of Porcellio scaber (Crustacea: Isopoda) in different physiological conditions.
We investigated the morphometric characteristics of the hepatopancreatic epithelium in the terrestrial isopod Porcellio scaber during acclimatization to laboratory conditions, during the daily cycle, the molt cycle, and fasting. The hepatopancreatic epithelium was analyzed using computer-assisted microscopy of serial sections of the hepatopancreatic tubes. In addition, the abundance, the distribution, and the size of lipid droplets in the hepatopancreatic epithelium were recorded. The experimental animals were collected in the field and transferred to the laboratory. The hepatopancreatic epithelium was thinner and lipid droplets reduced after 2 months of acclimatization to laboratory conditions. The daily cycle and the molt cycle affected neither the epithelial thickness nor the abundance of lipid droplets. But in animals fasted for 2 weeks, these two parameters were significantly reduced. Based on both the epithelial thickness and the abundance of lipid droplets in B cells, we propose criteria for estimating the stress status of the animals. With the possibility to determine the stress status, many studies on isopods gain in relevance.


Emerging, evolving, and established infectious diseases and interventions.
Planning, implementing, and evaluating interventions against infectious diseases depend on the nature of the infectious disease; the availability of intervention measures; and logistical, economic, and political constraints. Infectious diseases and vaccine- or drug-based interventions can be loosely categorized by the degree to which the infectious disease and the intervention are well established. Pertussis, polio, and measles are three examples of long-known infectious diseases for which global vaccination has dramatically reduced the public health burden. Pertussis vaccination was introduced in the 1940s, polio vaccination in the 1950s, and measles vaccination in the 1960s, nearly eliminating these diseases in many places.


S100A7 (psoriasin) expression is associated with aggressive features and alteration of Jab1 in ductal carcinoma in situ of the breast.
The S100A7 (psoriasin) gene is highly expressed in ductal carcinoma in situ (DCIS) of the breast and can be downregulated in invasive carcinoma. Persistent S100A7 expression in invasive carcinoma is associated with a worse prognosis, and this effect may be mediated in part through interaction with the multifunctional cell signaling protein Jab1. In order to investigate the relationship between S100A7 and progression from DCIS to invasive carcinoma, we studied S100A7 expression in 136 patients with DCIS (including 46 patients with associated invasive carcinoma) by immunohistochemistry. S100A7 expression was present in 63 out of 136 (46%) of DCIS lesions and was associated with estrogen receptor negative status (P = 0.0002), higher nuclear grade (P < 0.0001), necrosis (P < 0.0001) and inflammation (P < 0.0001). S100A7 status was no different between DCIS with and DCIS without an invasive component, but higher levels of S100A7 were present in DCIS associated with invasive carcinoma (P < 0.004). Analysis of a subset of cases showed that S100A7 expression was also associated with an increase in nuclear Jab1 (n = 43; P = 0.0019) and reduced p27kip1 (n = 47; P = 0.0168). In cases of DCIS associated with invasive carcinoma, there was also a significant reduction in S100A7 between in situ and invasive components (n = 46; P < 0.0001). In pure DCIS cases treated by local excision, there was no difference in frequency of S100A7 expression between patients with recurrence of DCIS (n = 9) and those without (n = 36). The findings reported here suggest that, although S100A7 may not be a marker for recurrence of DCIS, it is associated with poor prognostic markers in DCIS and may influence progression of breast carcinoma through its interaction with and influence on Jab1.


PD-1/PD-L1 expression in pancreatic cancer and its implication in novel therapies.
Pancreatic cancer is the seventh leading cause of death in developed countries and it still has a poor prognosis despite intense research in the last 20 years. Immunotherapy is a relatively new strategy in cancer treatment. The aim of immunotherapy is to block the immunosuppressive effect of tumoral cells. The PD1/PD-L1 axis has an important role in the inhibition of effector T cells and the development of regulatory T cells (Tregs). Blocking these checkpoints, and also inhibitory signals, leads to apoptosis of Tregs and increased immune response of effector T cells against tumoral antigens. Unfortunately, pancreatic cancer is generally considered to be a non-immunogenic tumor. Thus PD-1/PD-L1 inhibitors demonstrated poor results in pancreatic cancer, excepting some patients with MSI/dMMR (microsatellite instability/deficient mismatch repair). Furthermore, pancreatic cancer has a particular microenvironment with a strong desmoplastic reaction, increased interstitial fluid pressure, hypoxic conditions, and acidic extracellular pH, which promote tumorigenesis and progression of the tumor. Mismatch repair deficiency (dMMR) is correlated with a high level of mutation-associated neoantigens, most recognized by immune cells which could predict a favorable response to anti-PD-1/PD-L1 therapy. PD-1/PD-L1 molecules could be also found as soluble forms (sPD-1, sPD-L1). These molecules have a potential role in the prognosis and treatment of pancreatic cancer.


Ways of experiencing participation and factors affecting the activity level after nonreconstructed anterior cruciate ligament injury: a qualitative study.
Phenomenographic, cross-sectional. To describe ways of experiencing participation in activities of individuals with a nonreconstructed anterior cruciate ligament injury and to describe the emotional aspects related to participation. Further, the objective was to explore factors affecting the activity level. The importance of assessing different factors (knee status, muscle performance, psychological factors, performance-based tests, and subjective rating of knee function) after an anterior cruciate ligament injury has been emphasized. However, the results of these assessments do not answer the question of how the individuals themselves experience their participation in activities. Semi-structured interviews were conducted with 19 strategically selected informants (age range, 18-43 years) who had sustained an anterior cruciate ligament injury 18 to 67 months previously. A phenomenographic approach, which describes individuals' ways of experiencing a phenomenon, was used. Five qualitatively different categories were identified: (A) unconditioned participation, (B) participation as conditioned by risk appraisal, (C) participation as conditioned by experienced control of the knee, (D) participation as conditioned by experienced knee impairment, and (E) participation as conditioned by neglecting the knee injury. Within each category, 5 interrelated aspects were discerned: focus, level of performance, activities, strategies, and feelings. Categories A, C, and E reflected experiences of full participation, whereas categories B and D reflected experiences of modified participation. There were mostly positive feelings regarding participation. Negative feelings were expressed in category D. Factors affecting the activity level were grouped according to the framework of the International Classification of Functioning, Disability and Health and described as facilitating or hindering the activity level. Facilitating factors included regaining and maintaining physical function, regaining confidence in knee function, and learning/relearning movement patterns. Hindering factors included fear of injury/reinjury, uncontrollable giving way, and loss of motivation. With different strategies, most of the informants achieved a satisfactory activity level, despite impairments and decreased activity level. Both physical and psychological factors were described to affect the activity level, as well as time since injury.


Hybrid Coronary Revascularization - Current State of the Art.
Hybrid coronary revascularization (HCR) seeks to combine the benefit of surgical and nonsurgical techniques for optimum management for selective patients with multivessel obstructive coronary artery disease. The goal of HCR is to combine the benefit of surgical anastomosis of the left internal mammary artery to the left anterior descending coronary artery (LAD) graft along with stenting of non-LAD lesions with percutaneous coronary intervention (PCI). HCR usually involves the use of minimally invasive surgical techniques like robotically assisted coronary artery bypass graft (CABG), with the objective to produce a rapid recovery in the postoperative period, lower complications, and decreased length of stay in the hospital. In this review the authors seek to define the role of HCR in current practice including patient selection, techniques, logistics, outcome data and the challenges it faces in comparison to conventional CABG and PCI.


The Effects of Music Therapy on Cognition, Psychiatric Symptoms, and Activities of Daily Living in Patients with Alzheimer's Disease.
Alzheimer's disease (AD) is the most common type of dementia, affecting millions of older people worldwide. However, pharmacological therapies have not achieved desirable clinical efficacy in the past decades. Non-pharmacological therapies have been receiving increased attention to treat dementia in recent years. This study explores the effects of music therapy on cognitive function and mental wellbeing of patients with AD. A total number of 298 AD patients with mild, moderate, or severe dementia participated in the study. The participants with each grade of severity were randomly divided into three groups, which were a singing group, a lyric reading group, and a control group. These three groups received different interventions for three months. All participants underwent a series of tests on cognitive functions, neuropsychological symptoms, and activities of daily living at baseline, three months, and six months. The analysis shows that music therapy is more effective for improving verbal fluency and for alleviating the psychiatric symptoms and caregiver distress than lyrics reading in patients with AD. Stratified analysis shows that music therapy is effective for enhancing memory and language ability in patients with mild AD and reducing the psychiatric symptoms and caregiver distress in patients with moderate or severe AD. However, no significant effect was found for activities of daily living in patients with mild, moderate, or severe AD. This study suggests that music therapy is effective in enhancing cognitive function and mental wellbeing and can be recommended as an alternative approach to manage AD associated symptoms.


Associations of whole-grain, refined-grain, and fruit and vegetable consumption with risks of all-cause mortality and incident coronary artery disease and ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study.
Recent epidemiologic study results showed that subjects who had high intakes of whole-grain foods had lower risks of death and heart disease than did subjects who had low intakes. However, the findings were inconsistent for fruit and vegetable intake. The relations of whole-grain, refined-grain, and fruit and vegetable intakes with the risk of total mortality and the incidence of coronary artery disease (CAD) and ischemic stroke were studied in the Atherosclerosis Risk in Communities (ARIC) cohort (baseline: age 45-64 y, n = 15,792). Proportional hazards regression analyses were used to assess the relations of whole-grain, refined-grain, and fruit and vegetable intakes with the risk of death and the incidence of CAD and ischemic stroke, with adjustment for age, sex, ethnicity, energy intake, and cardiovascular disease risk factors. Dietary intakes were assessed by using a food-frequency questionnaire. Over an 11-y follow-up period, whole-grain intake was inversely associated with total mortality and incident CAD. The relative hazards of death for quintiles 2-5 of fruit and vegetable intake were 1.08 (95% CI: 0.88, 1.33), 0.94 (0.75, 1.17), 0.87 (0.68, 1.10), and 0.78 (0.61, 1.01), respectively; P for trend = 0.02. An inverse association between fruit and vegetable intake and CAD was observed among African Americans but not among whites (P for interaction = 0.01). The risk of ischemic stroke was not significantly related to whole-grain, refined-grain, or fruit and vegetable consumption. These observational findings suggest a beneficial effect of whole-grain and fruit and vegetable consumption on the risks of total mortality and incident CAD but not on the risk of ischemic stroke.


A Hebbian/Anti-Hebbian Neural Network for Linear Subspace Learning: A Derivation from Multidimensional Scaling of Streaming Data.
Neural network models of early sensory processing typically reduce the dimensionality of streaming input data. Such networks learn the principal subspace, in the sense of principal component analysis, by adjusting synaptic weights according to activity-dependent learning rules. When derived from a principled cost function, these rules are nonlocal and hence biologically implausible. At the same time, biologically plausible local rules have been postulated rather than derived from a principled cost function. Here, to bridge this gap, we derive a biologically plausible network for subspace learning on streaming data by minimizing a principled cost function. In a departure from previous work, where cost was quantified by the representation, or reconstruction, error, we adopt a multidimensional scaling cost function for streaming data. The resulting algorithm relies only on biologically plausible Hebbian and anti-Hebbian local learning rules. In a stochastic setting, synaptic weights converge to a stationary state, which projects the input data onto the principal subspace. If the data are generated by a nonstationary distribution, the network can track the principal subspace. Thus, our result makes a step toward an algorithmic theory of neural computation.


Reduced Risk of Hyperkalemia During Treatment of Heart Failure With Mineralocorticoid Receptor Antagonists by Use of Sacubitril/Valsartan Compared With Enalapril: A Secondary Analysis of the PARADIGM-HF Trial.
Consensus guidelines recommend the use of mineralocorticoid receptor antagonists (MRAs) for selected patients with symptomatic heart failure and reduced ejection fraction (HFrEF) to reduce morbidity and mortality; however, the use of MRAs in combination with other inhibitors of the renin-angiotensin-aldosterone system increases the risk of hyperkalemia. To determine whether the risk of hyperkalemia associated with use of MRAs for patients with HFrEF is reduced by sacubitril/valsartan in comparison with enalapril. The PARADIGM-HF (Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial randomly assigned 8399 patients with chronic HF, New York Heart Association class II to IV symptoms, and a left ventricular EF of 40% or less to treatment with enalapril 10 mg twice daily or sacubitril/valsartan 97/103 mg twice daily (previously known as LCZ696 [200 mg twice daily]) in addition to guideline-directed medical therapy. Use of MRAs was encouraged but left to the discretion of study investigators. Serum potassium level was measured at every study visit. The incidence of hyperkalemia (potassium level >5.5 mEq/L) and severe hyperkalemia (potassium level >6.0 mEq/L) among patients treated or not treated with an MRA at baseline and the risk of subsequent hyperkalemia for those newly treated with an MRA during study follow-up were defined in time-updated Cox proportional hazards models. Analyses were conducted between August 1 and October 15, 2016. Incident hyperkalemia and severe hyperkalemia. In comparison with the 3728 patients (44.4% of enrolled participants [21.6% female]) not taking an MRA at baseline, the 4671 patients (55.6% [22.0% female]) taking an MRA tended to be younger, with a lower EF, lower systolic blood pressure, and more advanced HF symptoms. Among those taking an MRA at baseline, the overall rates of hyperkalemia were similar between treatment groups, but severe hyperkalemia was more common in patients randomly assigned to enalapril than to sacubitril/valsartan (3.1 vs 2.2 per 100 patient-years; HR, 1.37 [95% CI, 1.06-1.76]; P = .02). In analyses including patients who newly started taking MRAs during the PARADIGM-HF trial, severe hyperkalemia remained more common in those randomly assigned to enalapril than to those randomly assigned to sacubitril/valsartan (3.3 vs 2.3 per 100 patient-years; HR, 1.43 [95% CI, 1.13-1.81]; P = .003). Among MRA-treated patients with symptomatic HFrEF, severe hyperkalemia is more likely during treatment with enalapril than with sacubitril/valsartan. These data suggest that neprilysin inhibition attenuates the risk of hyperkalemia when MRAs are combined with other inhibitors of the renin-angiotensin-aldosterone system in patients with HF. clinicaltrials.gov Identifier: NCT01035255.


Analysis of a draft genome sequence of Kitasatospora cheerisanensis KCTC 2395 producing bafilomycin antibiotics.
Kitasatospora cheerisanensis KCTC 2395, producing bafilomycin antibiotics belonging to plecomacrolide group, was isolated from a soil sample at Mt. Jiri, Korea. The draft genome sequence contains 8.04 Mb with 73.6% G+C content and 7,810 open reading frames. All the genes for aerial mycelium and spore formations were confirmed in this draft genome. In phylogenetic analysis of MurE proteins (UDP-N-acetylmuramyl-(L)-alanyl-(D)-glutamate:DAP ligase) in a conserved dcw (division of cell wall) locus, MurE proteins of Kitasatospora species were placed in a separate clade between MurEs of Streptomyces species incorporating (LL)-diaminopimelic acid (DAP) and MurEs of Saccharopolyspora erythraea as well as Mycobacterium tuberculosis ligating meso-DAP. From this finding, it was assumed that Kitasatospora MurEs exhibit the substrate specificity for both (LL)-DAP and meso-DAP. The bafilomycin biosynthetic gene cluster was located in the left subtelomeric region. In 71.3 kb-long gene cluster, 17 genes probably involved in the biosynthesis of bafilomycin derivatives were deduced, including 5 polyketide synthase (PKS) genes comprised of 12 PKS modules.


Functional paclitaxel plus honokiol micelles destroying tumour metastasis in treatment of non-small-cell lung cancer.
Treatment effect of chemotherapy for aggressive non-small-cell lung cancer (NSCLC) is usually unsatisfactory for non-selective distributions of anticancer drugs, generation of vasculogenic mimicry (VM) channels, high metastasis and recurrence rate. Therefore, we developed a kind of dequalinium (DQA) modified paclitaxel plus honokiol micelles in this study to destroy VM channels and inhibit tumour metastasis. In vitro assays indicated that the targeting paclitaxel micelles with ideal physicochemical characteristics could exhibit not only the powerful cytotoxicity on Lewis lung tumour (LLT) cells but also the effective suppression on VM channels and tumour metastasis. Action mechanism studies manifested that DQA modified paclitaxel plus honokiol micelles could activate apoptotic enzymes caspase-3 and caspase-9 as well as down-regulate FAK, PI3K, MMP-2 and MMP-9. In vivo assays indicated that polymeric micelles could increase selective accumulation of chemotherapeutic drugs at tumour sites and showed a conspicuous antitumour efficacy. Hence, the DQA modified paclitaxel plus honokiol micelles prepared in this study provided a potential treatment strategy for NSCLC.


Reboxetine in therapy-resistant enuresis: A randomized placebo-controlled study.
A significant minority of children with enuresis do not respond to either desmopressin or the enuresis alarm. Anticholinergics have not proven as successful as expected. The fourth evidence-based treatment, the tricyclic antidepressant imipramine, is cardiotoxic when overdosed, which has led to diminished use. The aim was to determine whether there is a role for the noradrenergic antidepressant reboxetine, as monotherapy or combined with desmopressin, in the treatment of enuresis in children who have not responded to standard therapy, and whether there are side effects involved. We also sought prognostic factors in anamnestic data and in the voiding chart. The study was a randomized placebo-controlled study with a double-blind cross-over design, in which all patients underwent treatment during three 4-week periods, one with reboxetine 4 mg and placebo, one with reboxetine 4 mg and desmopressin, and one with double placebo treatment. The proportion of wet nights out of 14 was compared before treatment and during the last 2 weeks of each treatment period. Eighteen patients were included. The reduction of wet nights was much better with either reboxetine in monotherapy or in combination with desmopressin than during the placebo period (p = 0.002) (Figure). However, only one patient achieved complete dryness, this during monotherapy. There were three intermediate responders to monotherapy and five to combination treatment. With reboxetine in monotherapy, six children experienced negative side effects compared with three with combination therapy, and two with placebo. All of these side effects were mild and reversible. Only one patient chose to cease treatment because of side effects. No prognostic factors were found in either the case history or in voiding chart data. The present study, the first placebo-controlled trial, confirms that reboxetine is an evidence-based alternative to cardiotoxic antidepressant treatment in therapy-resistant enuresis. The fact that few patients achieved complete dryness may be due to the low dosage used. In our clinical practice we increase the dose to 8 mg when dryness is not achieved with the lower dose. Our experience is that this leaves more children with full response, but the evidence of this has yet to be shown. Reboxetine seems to be an alternative in the treatment of enuretic children who have not responded to standard treatment.


Ammonium increases Ca(2+) signalling and upregulates expression of Cav1.2 gene in astrocytes in primary cultures and in the in vivo brain.
The primary aim of this study was to identify the effects of hyperammonaemia on functional expression of Cav1.2 L-type Ca(2+) channels in astroglia. Primary cultures of mouse astrocytes were used to study effects of chronic treatment (1-5 days) with ammonium chloride, at 1, 3 and 5 mm on depolarization-induced increases in free cytosolic Ca(2+) concentration ([Ca(2+)]i , measured with Fura-2 based microfluorimetry) in control conditions and following treatment with the L-type Ca(2+) channel inhibitor, nifedipine, or with ryanodine receptor inhibitor, ryanodine. Expression of Cav1.2 mRNA was identified with RT-PCR, whereas protein content was determined by Western blotting. Sustained hyperammonaemia in vivo was induced by daily injections of urease (33 units kg body weight(-1), i.p.) for 3 days. Depolarization-induced [Ca(2+)]i transients sensitive to nifedipine (peak of the response) and to ryanodine (plateau phase) were significantly increased in astrocytes chronically exposed to ammonium. The ammonium-induced increase in Ca(2+) influx in astrocytes resulted from an upregulation of Cav1.2 channel's expression detected at mRNA and protein levels. Increase in Cav1.2 expression was prevented by ouabain antagonist canrenone. Similar upregulation of Cav1.2 gene expression was found in the brains of adult mice subjected to intraperitoneal injection of urease. In transgenic mice tagged with an astrocyte-specific or neurone-specific markers and treated with intraperitoneal injections of urease, the fluorescence-activated cell sorting of neurones and astrocytes demonstrated that Cav1.2 mRNA expression was upregulated in astrocytes, but not in neurones. Ammonium-induced deregulation of astroglial Ca(2+) signalling, is, in part, associated with upregulation of Cav1.2 L-type calcium channels.


Rationally designed haptens for highly sensitive monoclonal antibody-based immunoanalysis of fenhexamid.
Immunochemical methods have been consolidated during the last few years as complementary analytical strategies for chemical contaminant and residue determination. However, generation of suitable immunoreagents for small organic molecules demands adequate hapten design. In this study, fenhexamid was considered as a model compound and novel haptens were designed and synthesized in order to evaluate the influence of the linker tethering site on antibody binding properties and immunoassay parameters. Haptens were conceived with the spacer arm at different positions, while the more antigenic aromatic moiety was kept free. The synthesis of these functionalized compounds was accomplished by total construction of the molecule through several steps. This strategy afforded very high-affinity monoclonal antibodies specific of fenhexamid, with IC50 values around or below 0.1 nM. Using these novel immunoreagents, a direct competitive enzyme-linked immunosorbent assay with a remarkably low limit of detection (4 ng L-1) was developed for the determination of fenhexamid residues. The selected immunoassay was investigated in terms of trueness, precision, repeatability, and robustness. The QuEChERS extraction methodology was applied to fortified samples and recoveries between 83% and 113%, with relative standard deviations below 20%, were observed. Moreover, contaminated and blind spiked samples were measured by the developed immunoassay and by ultra-performance liquid chromatography coupled to tandem mass spectrometry, showing statistically comparable results.


Genome-wide analysis of the MYB transcription factor superfamily in soybean.
The MYB superfamily constitutes one of the most abundant groups of transcription factors described in plants. Nevertheless, their functions appear to be highly diverse and remain rather unclear. To date, no genome-wide characterization of this gene family has been conducted in a legume species. Here we report the first genome-wide analysis of the whole MYB superfamily in a legume species, soybean (Glycine max), including the gene structures, phylogeny, chromosome locations, conserved motifs, and expression patterns, as well as a comparative genomic analysis with Arabidopsis. A total of 244 R2R3-MYB genes were identified and further classified into 48 subfamilies based on a phylogenetic comparative analysis with their putative orthologs, showed both gene loss and duplication events. The phylogenetic analysis showed that most characterized MYB genes with similar functions are clustered in the same subfamily, together with the identification of orthologs by synteny analysis, functional conservation among subgroups of MYB genes was strongly indicated. The phylogenetic relationships of each subgroup of MYB genes were well supported by the highly conserved intron/exon structures and motifs outside the MYB domain. Synonymous nucleotide substitution (dN/dS) analysis showed that the soybean MYB DNA-binding domain is under strong negative selection. The chromosome distribution pattern strongly indicated that genome-wide segmental and tandem duplication contribute to the expansion of soybean MYB genes. In addition, we found that ~ 4% of soybean R2R3-MYB genes had undergone alternative splicing events, producing a variety of transcripts from a single gene, which illustrated the extremely high complexity of transcriptome regulation. Comparative expression profile analysis of R2R3-MYB genes in soybean and Arabidopsis revealed that MYB genes play conserved and various roles in plants, which is indicative of a divergence in function. In this study we identified the largest MYB gene family in plants known to date. Our findings indicate that members of this large gene family may be involved in different plant biological processes, some of which may be potentially involved in legume-specific nodulation. Our comparative genomics analysis provides a solid foundation for future functional dissection of this family gene.


Accuracy of direct gradient sensing by single cells.
Many types of cells are able to accurately sense shallow gradients of chemicals across their diameters, allowing the cells to move toward or away from chemical sources. This chemotactic ability relies on the remarkable capacity of cells to infer gradients from particles randomly arriving at cell-surface receptors by diffusion. Whereas the physical limits of concentration sensing by cells have been explored, there is no theory for the physical limits of gradient sensing. Here, we derive such a theory, using as models a perfectly absorbing sphere and a perfectly monitoring sphere, which, respectively, infer gradients from the absorbed surface particle density or the positions of freely diffusing particles inside a spherical volume. We find that the perfectly absorbing sphere is superior to the perfectly monitoring sphere, both for concentration and gradient sensing, because previously observed particles are never remeasured. The superiority of the absorbing sphere helps explain the presence at the surfaces of cells of signal-degrading enzymes, such as PDE for cAMP in Dictyostelium discoideum (Dicty) and BAR1 for mating factor alpha in Saccharomyces cerevisiae (budding yeast). Quantitatively, our theory compares favorably with recent measurements of Dicty moving up a cAMP gradient, suggesting these cells operate near the physical limits of gradient detection.


The MORPH algorithm: ranking candidate genes for membership in Arabidopsis and tomato pathways.
Closing gaps in our current knowledge about biological pathways is a fundamental challenge. The development of novel computational methods along with high-throughput experimental data carries the promise to help in the challenge. We present an algorithm called MORPH (for module-guided ranking of candidate pathway genes) for revealing unknown genes in biological pathways. The method receives as input a set of known genes from the target pathway, a collection of expression profiles, and interaction and metabolic networks. Using machine learning techniques, MORPH selects the best combination of data and analysis method and outputs a ranking of candidate genes predicted to belong to the target pathway. We tested MORPH on 230 known pathways in Arabidopsis thaliana and 93 known pathways in tomato (Solanum lycopersicum) and obtained high-quality cross-validation results. In the photosynthesis light reactions, homogalacturonan biosynthesis, and chlorophyll biosynthetic pathways of Arabidopsis, genes ranked highly by MORPH were recently verified to be associated with these pathways. MORPH candidates ranked for the carotenoid pathway from Arabidopsis and tomato are derived from pathways that compete for common precursors or from pathways that are coregulated with or regulate the carotenoid biosynthetic pathway.


Sulfation of minoxidil by multiple human cytosolic sulfotransferases.
Minoxidil is an antihypertensive agent and hair growth promoter that is metabolized by sulfation to the active compound, minoxidil sulfate. Thermostable phenol sulfotransferase (TS PST or P-PST) was initially thought to catalyze the reaction, and the enzyme was designated minoxidil sulfotransferase (MNX-ST). Information about human ST activities toward minoxidil would be useful in developing the capacity to predict individual responses to minoxidil based on tissue levels of STs. Therefore, human STs were studied from platelet homogenates, partially purified platelets, scalp skin high speed supernatants and COS-1 cell cDNA expressed preparations using a radiochemical enzymatic assay with minoxidil as the substrate. Studies showed the presence of TS PST, TL (thermolabile) PST and MNX-ST activities in human scalp skin. Biochemical properties and correlation studies suggested that in addition to TS PST, the TL PST activity, another ST activity or both were involved in the reaction. Partially purified human platelet TL PST tested with minoxidil and dopamine showed identical thermal stabilities and similar responses to the inhibitors 2,6-dichloro-4-nitrophenol (DCNP) and NaCl. To characterize the activity of TL PST toward minoxidil, several biochemical properties of the enzyme expressed from a human liver cDNA clone were investigated. When assayed with minoxidil and dopamine, thermal stabilities of the expressed enzyme were identical and IC50 values for the inhibitors DCNP and NaCl were similar. It was also demonstrated that cDNA encoded human liver dehydroepiandrosterone sulfotransferase and estrogen sulfotransferase contributed to the sulfation of minoxidil. The results confirm that at least four human STs contribute to minoxidil sulfation. MNX-ST activity represents a combination of ST activities. The data indicate that multiple ST activities should be taken into account in attempts to predict the regulation of minoxidil sulfation and individual responses to minoxidil.


Aging impairs protein-synthesis-dependent long-term memory in Drosophila.
Although aging is known to impair intermediate-term memory in Drosophila, its effect on protein-synthesis-dependent long-term memory (LTM) is unknown. We show here that LTM is impaired with age, not due to functional defects in synaptic output of mushroom body (MB) neurons, but due to connectivity defects of dorsal paired medial (DPM) neurons with their postsynaptic MB neurons. GFP reconstitution across synaptic partners (GRASP) experiments revealed structural connectivity defects in aged animals of DPM neurons with MB axons in the α lobe neuropil. As a consequence, a protein-synthesis-dependent LTM trace in the α/β MB neurons fails to form. Aging thus impairs protein-synthesis-dependent LTM along with the α/β MB neuron LTM trace by lessening the connectivity of DPM and α/β MB neurons.


Definitive Chemoradiotherapy in Elderly Cervical Cancer Patients: A Multiinstitutional Analysis.
The aim of the study was to investigate the prognostic factors for survival and treatment-related toxicities in older (≥65 years) cervical cancer patients treated with definitive chemoradiotherapy. In addition, we sought to compare the outcomes between the older elderly (≥75 years) and their younger old counterparts (age, 65-74 years). We retrospectively reviewed medical records from 269 biopsy-proven nonmetastatic cervical cancer patients treated with external radiotherapy and intracavitary brachytherapy at the departments of radiation oncology in 2 different universities. The prognostic factors for survival, local control, and distant metastasis (DM) were analyzed. The median follow-up time was 38.8 months (range, 1.5-175.5 months) for the entire cohort and 70.0 months (range, 6.1-175.7 months) for survivors. The 2- and 5-year overall survival (OS), disease-free survival (DFS), and cause-specific survival rates were 66% and 42%, 63% and 39%, and 72% and 55%, respectively. Patients 75 years or older showed significantly worse OS compared with patients aged 65 to 74 years but showed no significant difference in DFS. The 2- and 5-year local control rates were 86% and 71%, respectively. The incidences of DMs at 2 and 5 years were 22% and 30%, respectively. In multivariate analysis, vaginal infiltration and lymph node metastasis were predictive of OS, DFS, local recurrence, and DM. Concomitant chemotherapy was predictive of OS, DFS, and local recurrence, and larger tumor (>4 cm) was a significant prognostic factor for local recurrence. None of the patients had toxicity that necessitated the discontinuation of radiotherapy. All patients were evaluable for acute toxicity, and no grade higher than 3 adverse events occurred during external beam radiation therapy or brachytherapy. Although age limited the delivery of aggressive treatment, concurrent chemoradiotherapy in elderly patients associated with improved outcomes similar as in younger counterparts without increasing serious acute and late toxicities.


Diagnostic Performance of a 10-Minute Gadolinium-Enhanced Brain MRI Protocol Compared with the Standard Clinical Protocol for Detection of Intracranial Enhancing Lesions.
The development of new MR imaging scanners with stronger gradients and improvement in coil technology, allied with emerging fast imaging techniques, has allowed a substantial reduction in MR imaging scan times. Our goal was to develop a 10-minute gadolinium-enhanced brain MR imaging protocol with accelerated sequences and to evaluate its diagnostic performance compared with the standard clinical protocol. Fifty-three patients referred for brain MR imaging with contrast were scanned with a 3T scanner. Each MR image consisted of 5 basic fast precontrast sequences plus standard and accelerated versions of the same postcontrast T1WI sequences. Two neuroradiologists assessed the image quality and the final diagnosis for each set of postcontrast sequences and compared their performances. The acquisition time of the combined accelerated pre- and postcontrast sequences was 10 minutes and 15 seconds; and of the fast postcontrast sequences, 3 minutes and 36 seconds, 46% of the standard sequences. The 10-minute postcontrast axial T1WI had fewer image artifacts (P < .001) and better overall diagnostic quality (P < .001). Although the 10-minute MPRAGE sequence showed a tendency to have more artifacts than the standard sequence (P = .08), the overall diagnostic quality was similar (P = .66). Moreover, there was no statistically significant difference in the diagnostic performance between the protocols. The sensitivity, specificity, and accuracy values for the 10-minute protocol were 100.0%, 88.9%, and 98.1%. The 10-minute brain MR imaging protocol with contrast is comparable in diagnostic performance with the standard protocol in an inpatient motion-prone population, with the additional benefits of reducing acquisition times and image artifacts.


Marginal excision of cutaneous mast cell tumors in dogs was not associated with a higher rate of complications or prolonged wound healing than marginal excision of soft tissue sarcomas.
To compare wound healing following planned marginal excision of cutaneous mast cell tumors (MCTs) with that of soft tissue sarcomas (STSs) and to identify risk factors for wound healing complications and delay in healing. 126 dogs that underwent intentional marginal excision of cutaneous MCTs (n = 77) or subcutaneous STSs (49). Medical records of included dogs were reviewed and signalment, tumor size, tumor location, skin closure type, time to healing, reported complications, histopathological grade, and surgical margins were recorded. These variables and outcomes (complication rate and time to complete healing) were compared between dogs in the MCT and STS groups. Potential risk factors for complications and delayed healing were analyzed. No significant difference between the groups was found in any of the variables. Wound healing complication rates were 29% (22/77) for the MCT group and 31% (15/49) for the STS group. The mean ± SD time to complete healing was 16.5 ± 7.5 days for the MCT group and 17.7 ± 9.3 days for the STS group. These outcomes did not differ significantly between groups. For both groups, the use of subdermal plexus flap reconstruction was associated with the development of complications and increased time to complete healing. Marginal excision of cutaneous MCTs was not associated with a higher rate of complication or prolonged wound healing, compared with marginal excision of STSs. The use of flap reconstruction in skin closure may delay healing and planned adjuvant therapy. Owners should be counseled regarding these risks and where appropriate and feasible, surgery without reconstruction should be considered.