Strategies to maximize the performance of a STED microscope.
In stimulated emission depletion (STED) microscopy, the spatial resolution scales as the inverse square root of the STED beam's intensity. However, to fully exploit the maximum effective resolution achievable for a given STED beam's intensity, several experimental precautions have to be considered. We focus our attention on the temporal alignment between the excitation and STED pulses and the polarization state of the STED beam. We present a simple theoretical framework that help to explain their influence on the performance of a STED microscope and we validate the results by imaging calibration and biological samples with a custom made STED architecture based on a supercontinuum laser source. We also highlight the advantages of using time gating detection in terms of temporal alignment.


Dermoscopy report: proposal for standardization. Results of a consensus meeting of the International Dermoscopy Society.
Dermoscopy can assist clinicians in the evaluation and diagnosis of skin tumors. Since dermoscopy is becoming widely accepted and used in the medical community, there is now the need for a standardized method for documenting dermoscopic findings so as to be able to effectively communicate such information among colleagues. Toward this end, the International Dermoscopy Society embarked on creating a consensus document for the standardization and recommended criteria necessary to be able to effectively convey dermoscopic findings to consulting physicians and colleagues. The Dermoscopy Report Steering Committee created an extensive list of dermoscopic criteria obtained from an exhaustive search of the literature. A preliminary document listing all the dermoscopic criteria that could potentially be included in a standardized dermoscopy report was elaborated and presented to the members of the International Dermoscopy Society Board in two meetings of the Society and subsequently discussed via Internet communications between members and the Steering Committee. A consensus document including 10 points categorized as either recommended or optional and a template of the dermoscopy report were obtained. The final items included in the document are as follows: (1) patient's age, relevant history pertaining to the lesion, pertinent personal and family history (recommended); (2) clinical description of the lesion (recommended); (3) the two-step method of dermoscopy differentiating melanocytic from nonmelanocytic tumors (recommended); (4) the use of standardized terms to describe structures as defined by the Dermoscopy Consensus Report published in 2003. For new terms it would be helpful to provide a working definition (recommended); (5) the dermoscopic algorithm used should be mentioned (optional); (6) information on the imaging equipment and magnification (recommended); (7) clinical and dermoscopic images of the tumor (recommended); (8) a diagnosis or differential diagnosis (recommended); (9) decision concerning the management (recommended); (10) specific comments for the pathologist when excision and histopathologic examination are recommended (optional). The limitations of this study are those that are intrinsic of a consensus document obtained from critical review of the literature and discussion by opinion leaders in the field. Although it may be acceptable for a consulting physician to only state the dermoscopic diagnosis, the proposed standardized reporting system, if accepted and utilized, will make it easier for consultants to communicate with each other more effectively.


Malaria control in complex emergencies: the example of East Timor.
Malaria control in complex emergencies forms part of the World Health Organization's Roll Back Malaria (RBM) initiative. The underlying principle is a partnership with other UN agencies and non-governmental organizations, with the RBM programme providing support to its implementing partners through a Technical Support Network. This innovative approach was applied for the first time in 1999-2000, following the return of stability and security to East Timor. The RBM programme assessed the malaria situation during the acute emergency phase and identified programme priorities. Two non-governmental organizations were subsequently invited to operate as implementing partners. Individual proposals were developed and funding obtained, but no overall organizational and planning framework was established. Implementation commenced quickly, addressing aspects of prevention, diagnosis and treatment. As East Timor progressed into the transitional phase towards independence, the programme was not realigned to the changing context. Absence of monitoring and evaluation was a significant factor contributing to the resulting continuation of emergency malaria control activities well into the transitional phase. East Timor's example of malaria control in complex emergencies provides important lessons: (i). partnership roles and responsibilities should be clearly defined from the beginning of the programme, (ii). planning, monitoring and evaluation should be instigated from the start with the aim to develop long-term strategies and policies, (iii). expert support is necessary to guide implementation at all stages, (iv). the flexibility to react to changing priorities should be ensured as the context of the emergency and the available health structure changes, and (v). the implementation process, and alternatives for continuation of activities once the RBM complex emergency partnership has terminated, should be clarified to all partners involved.


Emergency department triage revisited.
Triage is a process that is critical to the effective management of modern emergency departments. Triage systems aim, not only to ensure clinical justice for the patient, but also to provide an effective tool for departmental organisation, monitoring and evaluation. Over the last 20 years, triage systems have been standardised in a number of countries and efforts made to ensure consistency of application. However, the ongoing crowding of emergency departments resulting from access block and increased demand has led to calls for a review of systems of triage. In addition, international variance in triage systems limits the capacity for benchmarking. The aim of this paper is to provide a critical review of the literature pertaining to emergency department triage in order to inform the direction for future research. While education, guidelines and algorithms have been shown to reduce triage variation, there remains significant inconsistency in triage assessment arising from the diversity of factors determining the urgency of any individual patient. It is timely to accept this diversity, what is agreed, and what may be agreeable. It is time to develop and test an International Triage Scale (ITS) which is supported by an international collaborative approach towards a triage research agenda. This agenda would seek to further develop application and moderating tools and to utilise the scales for international benchmarking and research programmes.


Cognitive ability predicts objectively measured counterproductive work behaviors.
Over the past 2 decades, increasing attention has been directed at the relationship between individual differences and counterproductive work behaviors (CWB). However, most of this research has focused on personality variables as potential predictors of CWB; surprisingly little research has investigated the link between counterproductivity and cognitive ability. This study presents the first focal investigation of the cognitive ability-CWB relationship. The authors measured organizational and interpersonal CWB using organizational records of formally recorded incidents (e.g., destruction of property, physical violence). In a predictive study, for a large sample of law enforcement job applicants, a standardized psychometric test of cognitive ability predicted CWB, whereas educational attainment did not.


Limits to sustained energy intake. XVII. Lactation performance in MF1 mice is not programmed by fetal number during pregnancy.
Several studies have suggested that lactation performance may be programmed by the number of fetuses during pregnancy, whereas other studies indicate that processes during lactation are more important. As gestation litter size and litter size in lactation are usually strongly correlated, separating the roles of pregnancy and lactation in lactation performance is difficult. To break this link, we experimentally manipulated litter size of MF1 mice to five or 16 pups per litter by cross-fostering. Litter size and mass at birth were recorded on day 1 of lactation prior to litter size manipulation. Maternal body mass and food intake, litter size and litter mass were measured daily throughout. After weaning, the potential differential utilisation of body tissues of the mothers was investigated. Relationships between maternal mass and food intake, including asymptotic daily food intake at peak lactation, offspring traits and other maternal parameters suggested that the number of fetuses the females had carried during pregnancy had no effect on lactation performance. Litter mass increases depended only on maternal food intake, which was highly variable between individuals, but was independent of fetal litter size. The sizes of key organs and tissues like the liver and alimentary tract were not related to maximal food intake at peak lactation or to fetal litter size, but the masses of the pelage, mammary glands and retroperitoneal fat pad were. These data suggest that while growth of the mammary glands and associated structures may be initiated in gestation, and vary in relation to the number of placentas, the ultimate sizes and activities of the tissues depends primarily on factors during lactation.


Once-daily amikacin dosing in burn patients treated with continuous venovenous hemofiltration.
Amikacin clearance can be increased in burn injury, which is often complicated by renal insufficiency. Little is known about the impact of renal replacement therapies, such as continuous venovenous hemofiltration (CVVH), on amikacin pharmacokinetics. We retrospectively examined the clinical pharmacokinetics, bacteriology, and clinical outcomes of 60 burn patients given 15 mg/kg of body weight of amikacin in single daily doses. Twelve were treated with concurrent CVVH therapy, and 48 were not. The pharmacodynamic target of ≥10 for the maximum concentration of drug in serum divided by the MIC (C(max)/MIC) was achieved in only 8.5% of patients, with a small reduction of C(max) in patients receiving CVVH and no difference in amikacin clearance. Mortality and burn size were greater in patients who received CVVH. Overall, 172 Gram-negative isolates were recovered from the blood cultures of 39 patients, with amikacin MIC data available for 82 isolates from 24 patients. A 10,000-patient Monte Carlo simulation was conducted incorporating pharmacokinetic and MIC data from these patients. The cumulative fraction of response (CFR) was similar in CVVH and non-CVVH patients. The CFR rates were not significantly improved by a theoretical 20 mg/kg amikacin dose. Overall, CVVH did not appear to have a major impact on amikacin serum concentrations. The low pharmacodynamic target attainment appears to be primarily due to higher amikacin MICs rather than more rapid clearance of amikacin related to CVVH therapy.


Safety Planning With Marginalized Survivors of Intimate Partner Violence: Challenges of Conducting Safety Planning Intervention Research With Marginalized Women.
Intimate partner violence (IPV) disproportionately affects marginalized women in the United States. This calls for effective safety planning strategies to reduce the risk for future revictimization and address safety needs of survivors from marginalized groups. This review identified types of interventions that incorporated safety planning and were successful in reducing the risk for future revictimization among IPV survivors from diverse groups, examined elements of safety planning in effective interventions, and described challenges or limitations in safety planning intervention research with marginalized women. A systematic search of five databases was performed. The search resulted in inclusion of 17 studies for synthesis. The included studies were quantitative, U.S.-based, evaluated interventions with a safety planning component, and had an outcome of change in IPV. Effective interventions that incorporated safety planning were empowerment and advocacy focused. Elements included were comprehensive assessments of survivors' unique needs and situations, educating them about IPV, helping them identify threats to safety, developing a concrete safety plan, facilitating linkage with resources, providing advocacy services as needed, and conducting periodic safety check-ins. For survivors with mental and behavioral health issues, effective interventions included psychotherapeutic approaches along with safety planning to address survivors' co-occurring health care needs. Although most studies reported positive findings, there were limitations related to designs, methods, adequate inclusion, and representation of marginalized women and cultural considerations. This calls for additional research using rigorous and culturally informed approaches to establish an evidence base for effective interventions that specifically address the safety planning needs of marginalized survivors of IPV.


Mass Spectrometric Analysis of the Active Site Tryptic Peptide of Recombinant O6-Methylguanine-DNA Methyltransferase Following Incubation with Human Colorectal DNA Reveals the Presence of an O6-Alkylguanine Adductome.
Human exposure to DNA alkylating agents is poorly characterized, partly because only a limited range of specific alkyl DNA adducts have been quantified. The human DNA repair protein, O6-methylguanine O6-methyltransferase (MGMT), irreversibly transfers the alkyl group from DNA O6-alkylguanines (O6-alkGs) to an acceptor cysteine, allowing the simultaneous detection of multiple O6-alkG modifications in DNA by mass spectrometric analysis of the MGMT active site peptide (ASP). Recombinant MGMT was incubated with oligodeoxyribonucleotides (ODNs) containing different O6-alkGs, Temozolomide-methylated calf thymus DNA (Me-CT-DNA), or human colorectal DNA of known O6-MethylG (O6-MeG) levels. It was digested with trypsin, and ASPs were detected and quantified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. ASPs containing S-methyl, S-ethyl, S-propyl, S-hydroxyethyl, S-carboxymethyl, S-benzyl, and S-pyridyloxobutyl cysteine groups were detected by incubating MGMT with ODNs containing the corresponding O6-alkGs. The LOQ of ASPs containing S-methylcysteine detected after MGMT incubation with Me-CT-DNA was <0.05 pmol O6-MeG per mg CT-DNA. Incubation of MGMT with human colorectal DNA produced ASPs containing S-methylcysteine at levels that correlated with those of O6-MeG determined previously by HPLC-radioimmunoassay (r2 = 0.74; p = 0.014). O6-CMG, a putative O6-hydroxyethylG adduct, and other potential unidentified MGMT substrates were also detected in human DNA samples. This novel approach to the identification and quantitation of O6-alkGs in human DNA has revealed the existence of a human DNA alkyl adductome that remains to be fully characterized. The methodology establishes a platform for characterizing the human DNA O6-alkG adductome and, given the mutagenic potential of O6-alkGs, can provide mechanistic information about cancer pathogenesis.


Closed-loop resonant fiber optic gyro with an improved digital serrodyne modulation.
To widen the linear dynamic range and improve the linearity, a closed-loop resonant fiber optic gyro (RFOG) is proposed and experimentally demonstrated. To overcome the effect of the imperfect serrodyne modulation, an improved frequency shifting module is designed and constructed on a LiNbO3 phase modulator. Its frequency resolution is improved to 0.01 Hz which is equivalent to a rotation rate of 0.04°/h for an RFOG with a 12-cm diameter fiber ring resonator. With the frequency shifter applied in the RFOG, a closed-loop detection is demonstrated, whose bias stability is around 2 °/h, close to that of the open-loop output. Moreover, good linearity and wide dynamic range are also experimentally demonstrated thanks to the closed-loop operation. The measured result shows that the open-loop linear detection range of ± 215°/s is improved to ± 1076°/s. It is improved by a factor of 5. The open-loop scale factor nonlinearity of 1.2% is decreased to 0.02% (200 ppm), which is improved by a factor of 60. These are the best results reported to date, to the best of our knowledge, for closed-loop RFOGs.


Comparison of fourier-transform and data-dependent system profilometry by use of interferometric regeneration.
Fourier-transform profilometry (FTP) and data-dependent system profilometry (DDSP) are the two major phase-extraction methods that use a single interferogram. The difficulty in verifying surface profiles obtained by these methods is that the exact spot on an actual surface cannot be measured with two different instruments. An interferogram regeneration procedure is developed to solve this problem. The surface profile is then extracted from the regenerated interferogram by both FTP and DDSP. Comparisons of the actual surface profile with the extracted surface profiles show that both methods perform equally well in measuring the root mean square and the center line average, but only DDSP is able to reproduce the detailed surface profile of the reference surface.


Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients.
Anemia, a common complication of chronic kidney disease (CKD), has previously been attributed primarily to decreased production of erythropoietin. More recently, it has become apparent that the etiology of anemia involves several other factors, most notably dysfunctional iron metabolism, mediated via increased hepcidin activity and reduced clearance. Current management of anemia in patients with advanced CKD is based on erythropoiesis-stimulating agents and iron supplementation, along with red blood cell transfusions when necessary; however, safety considerations associated with these therapies highlight the need to pursue alternative treatment options targeting other mechanisms such as hypoxia-inducible factors (HIFs) that act as central regulators of erythropoiesis by coordinating a series of graded hypoxic responses. This review discusses the discovery of the HIF pathway and its regulation via HIF prolyl hydroxylase enzymes in the context of erythropoiesis and iron metabolism. The rationale for targeting this pathway and the clinical development of HIF prolyl hydroxylase inhibitors are reviewed, with a commentary on the potential implications of this class of agents in CKD anemia management. Key Messages: Pharmacologic activation of the HIF pathway results in a transient pseudo-hypoxic state that stimulates erythropoiesis in CKD patients with anemia. Results from clinical studies of a number of HIF prolyl hydroxylase inhibitors are increasingly available and provide support for the continued evaluation of the risk-benefit ratio of this novel therapeutic approach to the treatment of anemia in CKD.


Resveratrol enhances perforin expression and NK cell cytotoxicity through NKG2D-dependent pathways.
In a previous report, we showed that the in vivo cytotoxic activity of the natural killer (NK) cells isolated from resveratrol-pretreated rats is significantly enhanced compared with that of the non-pretreated rats; however, the underlying mechanism remains unclear. In the present study, we use cultured NK92 cell line to examine the possible signaling pathways underlying the resveratrol-induced activation. Using cultured K562, HepG2, and A549 cells as targets, we show that resveratrol pretreatment increases NK cell cytotoxicity in a dose-dependent manner. The enhanced cytotoxic effect is accompanied by increases in JNK and ERK-1/2 MAP kinase activity and perforin expression. Moreover, the expression of NKG2D, an upstream signaling molecule of the MAP kinases pathway, is also enhanced. Resveratrol-enhanced perforin expression and cytotoxic activity are effectively inhibited by pretreatment with the inhibitors of JNK (SP600125), ERK-1/2 (PD98059), or by siRNAs against JNK-1 and ERK-2. However, the inhibitors or siRNA to p38 exhibits no effect. Since IL-2 has been shown to induce NKG2D expression and perforin release, we therefore, examined whether IL-2 and resveratrol act in parallel. We show that IL-2 also stimulates perforin expression, however, when treated together with resveratrol, they exhibit no additive effect. The results suggest that in NK92 cells, resveratrol may act via a similar or overlapping pathway as that of IL-2, to enhance perforin expression and cytotoxic activity. Data presented strongly indicate that resveratrol act via NKG2D-dependent JNK and ERK-1/2 pathways.


Enhancement of the Antioxidant Activity and Neurotherapeutic Features through Pyridol Addition to Tetraazamacrocyclic Molecules.
Alzheimer's and other neurodegenerative diseases are chronic conditions affecting millions of individuals worldwide. Oxidative stress is a consistent component described in the development of many neurodegenerative diseases. Therefore, innovative strategies to develop drug candidates that overcome oxidative stress in the brain are needed. To target these challenges, a new, water-soluble 12-membered tetraaza macrocyclic pyridinophane L4 was designed and produced using a building-block approach. Potentiometric data show that the neutral species of L4 provides interesting zwitterionic behavior at physiological pH, akin to amino acids, and a nearly ideal isoelectric point of 7.3. The copper(II) complex of L4 was evaluated by X-ray diffraction and cyclic voltammetry to show the potential modes of antioxidant activity derived, which was also demonstrated by 2,2-diphenyl-1-picrylhydrazyl and coumarin carboxylic acid antioxidant assays. L4 was shown to have dramatically enhanced antioxidant activity and increased biological compatibility compared to parent molecules reported previously. L4 attenuated hydrogen peroxide (H2O2)-induced cell viability loss more efficiently than precursor molecules in the mouse hippocampal HT-22 cell model. L4 also showed potent (fM) level protection against H2O2 cell death in a BV2 microglial cell culture. Western blot studies indicated that L4 enhanced the cellular antioxidant defense capacity via Nrf2 signaling activation as well. Moreover, a low-cost analysis and high metabolic stability in phase I and II models were observed. These encouraging results show how the rational design of lead compounds is a suitable strategy for the development of treatments for neurodegenerative diseases where oxidative stress plays a substantial role.


Effect of Layer Directions on Internal Structures and Tensile Properties of 17-4PH Stainless Steel Parts Fabricated by Fused Deposition of Metals.
17-4PH stainless steel specimens were fabricated by fused deposition of metals (FDMet) technology, which combines 17-4PH particles with an organic binder. FDMet promises a low-cost additive manufacturing process. The present research aims to clarify the influence of layer directions in the 3D printing process on the mechanical and shrinkage properties of as-sintered and as-aged specimens. All specimens (the as-sintered and as-aged specimens printed in three layer directions) exhibited high relative density (97.5-98%). The highest ultimate strengths (880 and 1140 MPa in the as-sintered and as-aged specimens, respectively) were obtained when the layer direction was perpendicular to the tensile direction. Conversely, the specimens printed with their layer direction parallel to the tensile direction presented a low ultimate strength and low strain at breakage. The fact that the specimens with their layer direction parallel to the tensile direction presented a low ultimate strength and low strain at breakage is a usual behavior of parts obtained by means of FDM. The SEM images revealed oriented binder domains in the printed parts and oriented voids in the sintered parts. It was assumed that large binder domains in the filament were oriented perpendicular to the layer directions during the fused deposition modeling printing, and remained as oriented voids after sintering. Stress concentration in the oriented void defects was likely responsible for the poor tensile properties of these specimens.


Balanced inhibition and excitation drive spike activity in spinal half-centers.
Many limb movements are composed of alternating flexions and extensions. However, the underlying spinal network mechanisms remain poorly defined. Here, we show that the intensity of synaptic excitation and inhibition in limb motoneurons varies in phase rather than out of phase during rhythmic scratchlike network activity in the turtle. Inhibition and excitation peak with the total neuron conductance during the depolarizing waves of scratch episodes. Furthermore, spike activity is driven by depolarizing synaptic transients rather than pacemaker properties. These findings show that balanced excitation and inhibition and irregular firing are fundamental motifs in certain spinal network functions.


Identification of the mouse neuromuscular degeneration gene and mapping of a second site suppressor allele.
The nmd mouse mutation causes progressive degeneration of spinal motor neurons and muscle atrophy. We identified the mutated gene as the putative transcriptional activator and ATPase/DNA helicase previously described as Smbp2, Rip1, Gf1, or Catf1. Mutations were found in two alleles-a single amino acid deletion in nmdJ and a splice donor mutation in nmd2J. The selective vulnerability of motor neurons is striking in view of the widespread expression of this gene, although the pattern of degeneration may reflect a specific threshold since neither allele is null. In addition, the severity of the nmd phenotype is attenuated in a semidominant fashion by a major genetic locus on chromosome (Chr) 13. The identification of the nmd gene and mapping of a major suppressor provide new opportunities for understanding mechanisms of motor neuron degeneration.


Regulation of the integrin subunit alpha5 gene promoter by the transcription factors Sp1/Sp3 is influenced by the cell density in rabbit corneal epithelial cells.
Expression of the alpha5beta1 fibronectin (Fn) integrin is well recognized in the corneal epithelium and has been postulated to increase during wound healing. In the present study, the regulatory influence of the positive transcription factors Sp1/Sp3 on the activity directed by the promoter of the alpha5 gene was examined in rabbit corneal epithelial cells (RCECs) primary cultured at various cell densities. Expression of the alpha5 subunit was assessed at the transcriptional level by semiquantitative RT-PCR analyses. The regulatory elements necessary to direct expression of the alpha5 gene were identified by transfecting RCECs with recombinant plasmids bearing various lengths from the alpha5 gene promoter fused to the CAT reporter gene. Binding of Sp1/Sp3 to the alpha5 promoter was assessed by both electrophoretic mobility shift assays (EMSAs) and DNaseI footprinting. Endogenous levels of Sp1/Sp3 were determined by Western blot and supershift analyses. The regulatory influence exerted by Sp1/Sp3 on the alpha5 promoter was evaluated both by site-directed mutagenesis and cotransfection in Sp1-deficient Drosophila SL-2 Schneider cells. Subconfluent RCECs expressed nearly five times more alpha5 transcript than 48-hour postconfluent RCECs. The activity directed by the alpha5 promoter was found to be affected by cell density. Strong promoter activity was observed in subconfluent RCECs, whereas a dramatic repression was measured in postconfluent cells. EMSA and DNaseI footprinting provided evidence for the binding of Sp1 to both a proximal site located within the previously reported alpha5 fibronectin responsive element (FRE), and a distal site located between positions -117 and -101. Cotransfection experiments in Schneider cells, as well as transfection of RCECs with recombinant constructs bearing mutations into the distal Sp1 site, confirmed the positive regulatory influence of Sp1 on both the -42/-92 and -92/-132 alpha5 promoter segments. Most of all, EMSA and Western blot analyses demonstrated the expression of substantial amounts of Sp1/Sp3 in subconfluent but not postconfluent RCECs. These results provide support to the hypothesis that the strong reduction in the activity of the alpha5 promoter when RCECs reach a high cell density is the consequence of a reduced expression of Sp1/Sp3 under such cell culture conditions.


Sexual differentiation of galanin gene expression in gonadotropin-releasing hormone neurons.
In adult rats, only females are capable of generating an LH surge in response to high levels of ovarian steroids. This is because the ability to generate LH surges in adulthood in response to ovarian steroids is suppressed by high levels of testosterone during neonatal life. We have previously shown that galanin gene expression in GnRH neurons is induced by ovarian steroids in association with an LH surge, suggesting that galanin plays a role in the generation of the LH surge. If this is the case, then the induction of galanin gene expression in GnRH neurons in response to ovarian steroids might, like the LH surge itself, be sexually differentiated during the neonatal period. To test this hypothesis, we manipulated gonadal steroid levels in four groups of rat pups on the first day of life and looked at the ability of ovarian steroids to induce an LH surge and stimulate galanin gene expression in GnRH neurons of adult animals. The four groups consisted of female pups that were injected with either 10 micrograms of testosterone propionate (n = 6; testosterone-treated females) or vehicle (n = 6; control females) and male pups that were either castrated (n = 6; castrated males) or sham-castrated (n = 6; sham-castrated males). All animals were then gonadectomized at 59 or 60 days of age, except for the males that had been castrated neonatally. Seven weeks later, the animals were challenged with estradiol (E2) benzoate and progesterone (P) in a paradigm that reliably produces an LH surge. (The rats were injected sc with 15-30 micrograms of E2 on day 0 at 1030 h and 5 mg of P on day 2 at 1200 h.) The animals were then killed between 1800 h and 1840 h on day 2 at the time of the expected LH surge, and their brains were processed for double-label in situ hybridization to estimate cellular levels of galanin messenger RNA (mRNA) in GnRH neurons. We reconfirmed the classical observation that the ability to generate an LH surge in response to E2/P is suppressed by neonatal exposure to testosterone. Galanin mRNA levels in GnRH neurons showed a similar pattern: after E2/P priming, galanin mRNA levels in GnRH neurons were significantly higher in normal females and in males castrated neonatally than in normal males and in females treated with testosterone neonatally. These results demonstrate that the E2/P induction of galanin gene expression in GnRH neurons at the time of the LH surge is sexually differentiated during the neonatal period and suggest that the increase in galanin gene expression in GnRH neurons could be one of the mechanisms underlying the sex difference in gonadotropin release seen in rats.


The experience of black fathers concerning support for their wives/partners during labour.
The goal of this article was to describe the experience of black fathers concerning support for their wives/partners during labour. The research design entailed an exploratory, descriptive, qualitative study that was contextual to clinical nursing. A phenomenological approach to nursing research was utilized, whereby unstructured interviews were conducted with ten black fathers. Two groups of black fathers were purposively selected for the study. Group 1 consisted of fathers who provided support to their wives/partners during labour and Group 2 consisted of fathers who did not provide support during labour. A literature control was undertaken to verify and recontextualize data. The results indicate that most of the fathers in Group 1 experienced negative feelings of nervousness, helplessness and anxiety due to lack of information concerning childbirth. These were coupled with positive feelings such as excitement, overwhelming delight and a sense of miracle. Most of the fathers in Group 2 expressed a feeling of wanting to be there. Lack of information, fear and cultural factors were identified as stumbling blocks. Conclusions drawn from the study included positive attitudes that needed to be enhanced as well as negative attitudes that needed counteracting. The guidelines were based on overcoming the following: cultural taboos; lack of knowledge and fears concerning childbirth; lack of interest in childbirth; and childbirth being regarded as a woman's department.


The natural history of varices.
Variceal bleeding and its ensuing complications correlate positively with the severity of liver disease. The average risk of bleeding in patients with cirrhosis who have not previously bled is 30%, with a 50% mortality rate within 6 weeks. This mortality rate is the rationale for prophylaxis. However, although fatal bleeding causes 35% of all deaths, patients who die after the first episode of bleeding represent only 15% of patients with cirrhosis and varices. Portal and intravariceal pressure, the appearance of oesophageal varices on endoscopic examination, severity of liver disease and alcohol abuse are independent risk factors for the occurrence of the first bleeding episode. In sinusoidal portal hypertension, the presence of varices indicates a hepatic venous pressure gradient > or = 12 mmHg. Although hepatic venous pressure gradient tends to be higher in patients who bleed or have large varices, bleeding risk is not related linearly to pressure above this threshold. Tension on the variceal wall relative to varix radius may be critical and increasing variceal size, in conjunction with wall thinness, may favour rupture at lower intraluminal pressures. The North Italian Endoscopic Club's simplified index for the risk of a first bleeding episode is based on Child class, variceal size and presence of red wale markings, although there may be other independent risk factors. Abstention from alcohol can decrease variceal size and the number of cherry-red spots. Because large varices are unlikely to develop de novo within 2 years, biennial endoscopic screening is sufficient for patients without varices; annual endoscopy is recommended for those with small varices.(ABSTRACT TRUNCATED AT 250 WORDS)


Association of Partial versus Radical Nephrectomy with Subsequent Hypertension Risk Following Renal Tumor Resection.
We investigated the risks of new onset and worsened hypertension after radical vs partial nephrectomy. Using a national administrative database of privately and Medicare insured patients we performed a retrospective cohort study of 9,207 and 4,686 patients who underwent radical and partial nephrectomy, respectively, for a renal mass between January 1, 2007 and December 31, 2016. One-to-one propensity score matching was done to balance the surgical groups based on patient demographics, baseline comorbidities, current medications and surgery year. Primary outcomes included new onset hypertension among patients with no history of hypertension and worsened hypertension among patients with baseline hypertension. We performed subgroup analyses stratified by patient age (75 or greater vs less than 75 years) and the presence of baseline kidney disease. Incidence rates and Cox proportional hazards models were used to compare outcomes in matched cohorts. Among 3,106 propensity matched patients without preexisting hypertension radical nephrectomy was associated with a higher risk of new onset hypertension compared to partial nephrectomy (HR 1.40, 95% CI 1.22-1.60, p <0.001). Similarly among 6,250 propensity matched patients with hypertension prior to surgery radical nephrectomy was associated with a higher risk of worsening baseline hypertension (HR 1.18, 95% CI 1.10-1.26, p <0.001). Subgroup analyses were consistent with the main study findings of worsened hypertension (p for interaction ≥0.05). Radical nephrectomy was associated with a higher risk of new onset and worsened hypertension compared to partial nephrectomy, including among elderly patients and individuals with normal kidney function. Given prior noted associations between hypertension and noncancer related morbidity, our results further encourage the preferential use of partial nephrectomy to manage localized renal masses when technically feasible.


Isomers of Pyrene-Imidazole Compounds: Synthesis and Configuration Effect on Optical Properties.
Two pyrene-imidazole-based structural isomers, axisymmetric syn-PyDTI and centrosymmetric anti-PyDTI, have been easily produced and successfully separated in a one-pot reaction. Crystalline syn-PyDTI exhibited a 2-fold higher quantum efficiency than anti-PyDTI and displayed a much better performance in OLEDs with a ηc.max of 11.4 cd A(-1) (8.8 cd A(-1) for anti-PyDTI), although they possess the same apparent electronic structure. Observations revealed that the molecular excited-state properties are derived from distinct structural symmetries.


Autosomal Trisomy and Triploidy Are Corrected During Female Meiosis in Caenorhabditis elegans.
Trisomy and triploidy, defined as the presence of a third copy of one or all chromosomes, respectively, are deleterious in many species including humans. Previous studies have demonstrated that Caenorhabditis elegans with a third copy of the X chromosome are viable and fertile. However, the extra X chromosome was shown to preferentially segregate into the first polar body during oocyte meiosis to produce a higher frequency of euploid offspring than would be generated by random segregation. Here, we demonstrate that extra autosomes are preferentially eliminated by triploid C. elegans and trisomy IV C. elegans Live imaging of anaphase-lagging chromosomes and analysis of REC-8 staining of metaphase II spindles revealed that, in triploids, some univalent chromosomes do not lose cohesion and preferentially segregate intact into the first polar body during anaphase I, whereas other autosomes segregate chromatids equationally at anaphase I and eliminate some of the resulting single chromatids during anaphase II. We also demonstrate asymmetry in the anaphase spindle, which may contribute to the asymmetric segregation. This study reveals a pathway that allows aneuploid parents to produce euploid offspring at higher than random frequency.


A comparison of dung beetle (Coleoptera: Scarabaeidae) attraction to native and exotic mammal dung.
Although the preference of dung beetles (Coleoptera: Scarabaeidae) for specific types and conditions of dung has been given substantial attention, little has been done to investigate the potential effects of exotic mammal introduction for game farms or rewilding projects. We used pitfall traps baited with various native and exotic herbivore, carnivore, and omnivore dung to evaluate dung beetle preference in the Great Plains of North America. Additionally, we analyzed of the nutrient quality of each dung type. In total, 9,089 dung beetles from 15 species were captured in 2 yr of sampling. We found significant differences (P < 0.05) in mean dung beetle capture among omnivore, herbivore, and carnivore dung, as well as differences in individual species preference for dung type. Omnivore dung was the most attractive with chimpanzee and human dung having the highest mean capture (291.1 ± 27.6 and 287.5 ± 28.5 respectively). Carrion also was highly attractive with a mean of 231.9 ± 20.6 beetles per trap (N = 8). Our results suggest definitive local preference of carrion in Phanaeus vindex Macleay and Onthophagus hecate (Panzer), while the congener, O. pennsylvanicus (Harold), was rarely captured in carrion and highly preferred omnivore dung. Preference for a specific bait type does not appear to be correlated with dung quality, mammalian diet, or origin of mammal. Results suggest niche segregation by dung type among dung beetle species.


New Plant Breeding Techniques Under Food Security Pressure and Lobbying.
Different countries have different regulations for the approval and cultivation of crops developed by using new plant breeding technologies (NPBTs) such as gene editing. In this paper, we investigate the relationship between global food security and the level of NPBT regulation assuming a World Nation Official (WNO) proposes advice on global NPBT food policies. We show that a stricter NPBT food regulation reduces food security as measured by food availability, access, and utilization. We also find that political rivalry among interest groups worsens the food security status, given the NPBT food technology is more productive and the regulatory policy is influenced by lobbying. When the WNO aims to improve food security and weighs the NPBT food lobby contribution more than the non-NPBT food lobby's in the lobbying game, the total lobbying contributions will be the same for the WNO, and the NPBT food lobby will be more successful in the political process. The NPBT food lobby, however, under food security loses its advantage in the political competition, and this may result in a strict NPBT food policy. Under food security problems implementing stricter NPBT food regulations results in welfare losses. JEL Code: D04, D43, D72, P16.


Validation of the LittlEARS Auditory Questionnaire in cochlear implanted infants and toddlers.
The LittlEARS Auditory Questionnaire (LEAQ) has so far been validated to assess auditory development in groups of normal-hearing children in over 20 different languages. Considering the huge variability in auditory development of CI children, especially since candidacy criteria have been relaxed, additional evidence to validate the use of LEAQ scores in this particular population is needed. The aim of this study is to provide evidence for the reliability and validity of LEAQ scores for assessing the auditory development of CI infants and toddlers based on an evaluation of LEAQ's internal structure and its relation to other variables. The study was prospective, with sequential enrolment and within-subject repeated measures. It included 122 children with profound bilateral sensorineural hearing loss implanted at 6-22 months of age. All children were evaluated with the Polish version of LEAQ on the first day of CI activation and at each of four follow-up visits related to sound processor fitting. The study was undertaken in the light of current psychometric thinking about how assessment instruments should be validated. The main aim of the study was to obtain evidence for the validity of interpreting LEAQ measures from CI children in terms of auditory development. First, in order to collect evidence for score reliability and validity based on LEAQ's internal structure, the psychometric properties of LEAQ scores from CI children were determined. A second step was to confirm validity by investigating the effect of concomitant variables on LEAQ scores. Correlations between LEAQ score and duration of hearing aid (HA) use, and between LEAQ score and duration of CI use, were investigated. Additionally, group differences in LEAQ scores between: 1) early and late implanted children; 2) children with long and short HA experience prior to implantation; and 3) children who showed responses over a wide frequency range from using their HAs (prior to implantation) vs those who did not. On each of the five administrations of LEAQ, the item difficulty indices increased (meaning the items became easier) and over the series they progressively increased with a range of: 0.01-0.62, 0.03-0.92, 0.09-1.00, 0.26-1.00, and 0.52-1.00. At the same time, item-total correlations were in the ranges: 0.09-0.77, 0.26-0.62, 0.00-0.65, 0.00-0.65, and 0.00-0.67. Cronbach's alpha values were above 0.80 for all administrations. A positive correlation between LEAQ score and duration of HA use, and subsequent duration of CI use (hearing experience) was found. When the children were stratified into groups according to age at cochlear implantation, duration of HA use before implantation, and audibility provided by HAs prior to implantation, the differences between the groups were reflected in both their rate of auditory development and their LEAQ score. The interpretation of LEAQ scores from CI children in terms of auditory development was supported by the validity evidence of internal structure and from a logical relationship to other variables. (1) Psychometric properties - item difficulty, item-total correlations, and Cronbach's alpha values - indicate that LEAQ measures are highly consistent and reliably gauge the level of a CI child's auditory development. (2) There was a positive correlation between LEAQ scores and the duration of hearing experience with HAs and a later CI; similarly, there were significant differences between groups of children stratified according to the age at cochlear implantation, duration of HA use before implantation, and audibility provided by HAs prior to implantation, all of which demonstrate the expected relation between LEAQ score and concomitant variables.


Recent advances in understanding catalysis of protein folding by molecular chaperones.
Molecular chaperones are highly conserved proteins that promote proper folding of other proteins in vivo. Diverse chaperone systems assist de novo protein folding and trafficking, the assembly of oligomeric complexes, and recovery from stress-induced unfolding. A fundamental function of molecular chaperones is to inhibit unproductive protein interactions by recognizing and protecting hydrophobic surfaces that are exposed during folding or following proteotoxic stress. Beyond this basic principle, it is now clear that chaperones can also actively and specifically accelerate folding reactions in an ATP-dependent manner. We focus on the bacterial Hsp70 and chaperonin systems as paradigms, and review recent work that has advanced our understanding of how these chaperones act as catalysts of protein folding.


The Parasitoid Eretmocerus hayati Is Compatible with Barrier Cropping to Decrease Whitefly (Bemisia tabaci MED) Densities on Cotton in China.
The whitefly, Bemisia tabaci (Gennadius) cryptic species Mediterranean (MED), is a destructive insect pest worldwide. In order to contribute to controlling B. tabaci by non-chemical methods, we examined the possibility of using a combination of trap/barrier crops and a parasitoid natural enemy in cotton. We performed field experiments using cantaloupe (Cucumis melo) and sunflower (Helianthus annuus) as trap crops and maize (Zea mays) as a barrier crop combined with periodic releases of the parasitoid Eretmocerus hayati in Hebei Province, Northern China. All treatments significantly reduced immature whitefly densities. Parasitism rate was significantly higher in cotton plots intercropped with sunflower and with perimeter-planted cantaloupe. Adult whitefly density was negatively related to parasitoid abundance and was significantly lower in cotton plots intercropped with maize than in the control plots. Intercropping was more effective than perimeter-planting at reducing B. tabaci densities and increasing yield. Parasitoid dispersal was not hampered by barrier crops, indicating that the two methods of control are compatible. These results contribute to the development of integrated pest management methods against this important pest.


Reliability of specific physical examination tests for the diagnosis of shoulder pathologies: a systematic review and meta-analysis.
Shoulder pain in the general population is common and to identify the aetiology of shoulder pain, history, motion and muscle testing, and physical examination tests are usually performed. The aim of this systematic review was to summarise and evaluate intrarater and inter-rater reliability of physical examination tests in the diagnosis of shoulder pathologies. A comprehensive systematic literature search was conducted using MEDLINE, EMBASE, Allied and Complementary Medicine Database (AMED) and Physiotherapy Evidence Database (PEDro) through 20 March 2015. Methodological quality was assessed using the Quality Appraisal of Reliability Studies (QAREL) tool by 2 independent reviewers. The search strategy revealed 3259 articles, of which 18 finally met the inclusion criteria. These studies evaluated the reliability of 62 test and test variations used for the specific physical examination tests for the diagnosis of shoulder pathologies. Methodological quality ranged from 2 to 7 positive criteria of the 11 items of the QAREL tool. This review identified a lack of high-quality studies evaluating inter-rater as well as intrarater reliability of specific physical examination tests for the diagnosis of shoulder pathologies. In addition, reliability measures differed between included studies hindering proper cross-study comparisons. PROSPERO CRD42014009018.


Factors contributing to mandibular anterior crowding in the early mixed dentition.
The aim of this study was to uncover the possible factors contributing to mandibular anterior crowding in the early mixed dentition. Mandibular dental casts of 60 children in the early mixed dentition were divided into two groups according to the severity of mandibular anterior crowding. The space available for the mandibular permanent incisors, total incisor width, deciduous intercanine width, deciduous intermolar widths, permanent intermolar width, interalveolar width, and total arch length were compared between the crowded group (CG) and noncrowded group (NCG), and correlations with crowding were investigated. The mandibular deciduous intercanine width, mandibular deciduous intermolar widths, mandibular permanent intermolar width, mandibular interalveolar width, space available for the mandibular permanent incisors, and total arch length were significantly larger in the NCG. The total width of the four mandibular incisors did not differ significantly between CG and NCG. Significant inverse correlations were found between crowding and available space, deciduous intercanine width, deciduous intermolar widths, permanent intermolar width, and interalveolar width. Total incisor width was directly correlated with crowding. No significant correlation was found between crowding and total arch length. The results of this study suggested that individual variations play an important role in treatment planning. However, one must not overlook arch length discrepancies and transverse discrepancies in patients with mandibular anterior crowding.


Jump-Squat Performance and Its Relationship With Relative Training Intensity in High-Level Athletes.
To examine the relationship between the relative load in full squats and the height achieved in jump-squat (JS) exercises and to determine the load that maximizes the power output of high-level athletes. Fifty-one male high-level track-and-field athletes (age 25.2 ± 4.4 y, weight 77. ± 6.2 kg, height 179.9 ± 5.6 cm) who competed in sprinting and jumping events took part in the study. Full-squat 1-repetition-maximum (1-RM) and JS height (JH) with loads from 17 to 97 kg were measured in 2 sessions separated by 48 h. Individual regression analyses showed that JH (R2 = .992 ± .005) and the jump decrease (JD) that each load produced with respect to the unloaded countermovement jump (CMJ) (R2 = .992 ± 0.007) are highly correlated with the full-squat %1-RM, which means that training intensities can be prescribed using JH and JD values. The authors also found that the load that maximizes JS's power output was 0%RM (ie, unloaded CMJ). These results highlight the close relationship between JS performance and relative training intensity in terms of %1-RM. The authors also observed that the load that maximizes power output was 0%1-RM. Monitoring jump height during JS training could help coaches and athletes determine and optimize their training loads.


Effect of sub-lethal damage to juvenile colonies of massive Porites spp. under contrasting regimes of temperature and water flow.
In this study, juvenile colonies of massive Porites spp. (a combination of P. lutea and P. lobata) from the lagoon of Moorea (W 149°50', S 17°30') were damaged and exposed to contrasting conditions of temperature and flow to evaluate how damage and abiotic conditions interact to affect growth, physiological performance, and recovery. The experiment was conducted in April and May 2008 and consisted of two treatments in which corals were either undamaged (controls) or damaged through gouging of tissue and skeleton in a discrete spot mimicking the effects of corallivorous fishes that utilize an excavating feeding mode. The two groups of corals were incubated for 10 days in microcosms that crossed levels of temperature (26.7 and 29.6°C) and flow (6 and 21 cm s-1), and the response assessed as overall colony growth (change in weight), dark-adapted quantum yield of PSII (Fv/Fm), and healing of the gouged areas. The influence of damage on growth was affected by temperature, but not by flow. When averaged across flow treatments, damage promoted growth by 25% at 26.7°C, but caused a 25% inhibition at 29.6°C. The damage also affected Fv/Fm in a pattern that differed between flow speeds, with a 10% reduction at 6 cm s-1, but a 4% increase at 21 cm s-1. Regardless of damage, Fv/Fm at 21 cm s-1 was 11% lower at 26.7°C than at 29.6°C, but was unaffected by temperature at 6 cm s-1. The lesions declined in area at similar rates (4-5% day-1) under all conditions, although the tissue within them regained a normal appearance most rapidly at 26.7°C and 6 cm s-1. These findings show that the response of poritid corals to sub-lethal damage is dependent partly on abiotic conditions, and they are consistent with the hypothesis that following damage, calcification and photosynthesis can compete for metabolites necessary for repair, with the outcome affected by flow-mediated mass transfer. These results may shed light upon the ways in which poritid corals respond to biting by certain corallivorous fishes.


Antibiotic resistance in wild birds.
Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance.


Designing online health services for patients.
Patients are increasingly interacting with their healthcare system through online health services, such as patient portals and telehealth programs. Recently, Shabrabani and Mizrachi provided data outlining factors that are most important for users or potential users of these online services. The authors conclude convincingly that while online health services have great potential to be helpful to their users, they could be better designed. As patients and their families play an increasingly active role in their health care, online health services should be made easier for them to use and better suited to their health-related needs. Further, the online services should be more welcoming to people of all literacy levels and from all socioeconomic backgrounds.


Albumin conjugates and assemblies as versatile bio-functional additives and carriers for biomedical applications.
As the most abundant plasma protein, serum albumin has been extensively studied and employed for therapeutic applications. Despite its direct clinical use for the maintenance of blood homeostasis in various medical conditions, this review exclusively summarizes and discusses albumin-based bio-conjugates and assemblies as versatile bio-functional additives and carriers in biomedical applications. As one of the smallest-sized proteins in the human body, albumin is physiochemically stable and biochemically inert. Moreover, albumin is also endowed with abundant specific binding sites for numerous therapeutic compounds, which also endow it with superior bioactivities. Firstly, due to its small size and binding specificity, albumin alone or its derived assemblies can be utilized as competent drug carriers, which can deliver drugs through the enhanced permeability and retention (EPR) effect or actively target lesion sites through binding with gp60 and secreted protein acidic and rich in cysteine (SPARC) in tumor sites. Furthermore, its biochemical stability and inertness make it a safe and biocompatible coating material for use in biomedical applications. Albumin-based surface modifying additives can be used to functionalize both macro substrates (e.g. surfaces of medical devices or implants) and nanoparticle surfaces (e.g. drug carriers and imaging contrast agents). In this review, we elaborate on the synthesis and applications of albumin-based bio-functional coatings and drug carriers, respectively.


Construction of a BAC library and a physical map of a major QTL for CBB resistance of common bean (Phaseolus vulgaris L.).
A major quantitative trait loci (QTL) conditioning common bacterial blight (CBB) resistance in common bean (Phaseolus vulgaris L.) lines HR45 and HR67 was derived from XAN159, a resistant line obtained from an interspecific cross between common bean lines and the tepary bean (P. acutifolius L.) line PI319443. This source of CBB resistance is widely used in bean breeding. Several other CBB resistance QTL have been identified but none of them have been physically mapped. Four molecular markers tightly linked to this QTL have been identified suitable for marker assisted selection and physical mapping of the resistance gene. A bacterial artificial chromosome (BAC) library was constructed from high molecular weight DNA of HR45 and is composed of 33,024 clones. The size of individual BAC clone inserts ranges from 30 kb to 280 kb with an average size of 107 kb. The library is estimated to represent approximately sixfold genome coverage. The BAC library was screened as BAC pools using four PCR-based molecular markers. Two to seven BAC clones were identified by each marker. Two clones were found to have both markers PV-tttc001 and STS183. One preliminary contig was assembled based on DNA finger printing of those positive BAC clones. The minimum tiling path of the contig contains 6 BAC clones spanning an estimated size of 750 kb covering the QTL region.


Testing an unconventional mortality information source in the canton of Geneva Switzerland.
Mortality data are often unavailable, incomplete, and difficult to access for research and other purposes. Gaps in mortality data reports, particularly those detailing place of death, deprive healthcare professionals, decision-makers, and many others of the information that is needed to plan, implement, and evaluate interventions designed for purposes such as to assist people in achieving their preferred death place or reduce hospital utilization. Alternative methods of collecting reliable and valid data on death place may be needed. Our study primarily compared mortality data from a conventional information system (Federal Statistical Office) with mortality data collected using an unconventional system (funeral homes) over a 6-year period (2005-10) for the canton of Geneva Switzerland. Only a small average difference (4.8%) in death incidence was found. Death place data comparisons were also useful. This study suggests that the unconventional data from funeral homes provides reasonably reliable, valid, timely, and useful mortality data.


Lovastatin lactone may improve irritable bowel syndrome with constipation (IBS-C) by inhibiting enzymes in the archaeal methanogenesis pathway.
Methane produced by the methanoarchaeon Methanobrevibacter smithii ( M. smithii) has been linked to constipation, irritable bowel syndrome with constipation (IBS-C), and obesity. Lovastatin, which demonstrates a cholesterol-lowering effect by the inhibition of HMG-CoA reductase, may also have an anti-methanogenesis effect through direct inhibition of enzymes in the archaeal methanogenesis pathway. We conducted protein-ligand docking experiments to evaluate this possibility. Results are consistent with recent clinical findings. F420-dependent methylenetetrahydromethanopterin dehydrogenase ( mtd), a key methanogenesis enzyme was modeled for two different methanogenic archaea: M. smithii and Methanopyrus kandleri. Once protein models were developed, ligand-binding sites were identified. Multiple ligands and their respective protonation, isomeric and tautomeric representations were docked into each site, including F420-coenzyme (natural ligand), lactone and β-hydroxyacid forms of lovastatin and simvastatin, and other co-complexed ligands found in related crystal structures. 1) Generally, for each modeled site the lactone form of the statins had more favorable site interactions compared to F420; 2) The statin lactone forms generally had the most favorable docking scores, even relative to the native template PDB ligands; and 3) The statin β-hydroxyacid forms had less favorable docking scores, typically scoring in the middle with some of the F420 tautomeric forms. Consistent with these computational results were those from a recent phase II clinical trial ( NCT02495623) with a proprietary, modified-release lovastatin-lactone (SYN-010) in patients with IBS-C, which showed a reduction in symptoms and breath methane levels, compared to placebo. The lactone form of lovastatin exhibits preferential binding over the native-F420 coenzyme ligand in silico and thus could inhibit the activity of the key M. smithii methanogenesis enzyme mtd in vivo. Statin lactones may thus exert a methane-reducing effect that is distinct from cholesterol lowering activity, which requires HMGR inhibition by statin β-hydroxyacid forms.


The role of the cytoskeleton in sensing changes in gravity by nonspecialized cells.
A large body of evidence indicates that single cells in vitro respond to changes in gravity, and that this response might play an important role for physiological changes at the organism level during spaceflight. Gravity can lead to changes in cell proliferation, differentiation, signaling, and gene expression. At first glance, gravitational forces seem too small to affect bodies with the size of a cell. Thus, the initial response to gravity is both puzzling and important for understanding physiological changes in space. This also offers a unique environment to study the mechanical response of cells. In the past 2 decades, important steps have been made in the field of mechanobiology, and we use these advances to reevaluate the response of single cells to changes in gravity. Recent studies have focused on the cytoskeleton as initial gravity sensor. Thus, we review the observed changes in the cytoskeleton in a microgravity environment, both during spaceflight and in ground-based simulation techniques. We also evaluate to what degree the current experimental evidence supports the cytoskeleton as primary gravity sensor. Finally, we consider how the cytoskeleton itself could be affected by changed gravity. To make the next step toward understanding the response of cells to altered gravity, the challenge will be to track changes quantitatively and on short timescales.


FTO variant rs9939609 is associated with body mass index and waist circumference, but not with energy intake or physical activity in European- and African-American youth.
Genome-wide association studies found common variants in the fat mass and obesity-associated (FTO) gene associated with adiposity in Caucasians and Asians but the association was not confirmed in African populations. Association of FTO variants with insulin resistance and energy intake showed inconsistent results in previous studies. This study aimed to assess the influence of FTO variant rs9939609 on adiposity, insulin resistance, energy intake and physical activity in European - (EA) and African-American (AA) youth. We conducted a cross-sectional study in EA and AA youths. One thousand, nine hundred and seventy-eight youths (48.2% EAs, 47.1% male, mean age 16.5 years) had measures of anthropometry. Percent body fat (%BF) was measured by dual-energy X-ray absorptiometry, visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAAT) by magnetic resonance imaging. Energy intake and physical activity were based on self report from up to 7 24-hour recalls. Physical activity was also measured by accelerometry. FTO rs9939609 was significantly associated with body mass index (BMI) (P = 0.01), weight (P = 0.03) and waist circumference (P = 0.04), with per-allele effects of 0.4 kg/m2, 1.3 kg and 0.8 cm, respectively. No significant association was found between rs9939609 and %BF, VAT, SAAT or insulin resistance (P > 0.05), or between rs9939609 and energy intake or vigorous physical activity (P > 0.05). No significant interactions of rs9939609 with ethnicity, gender, energy intake or physical activity were observed (P > 0.05). The FTO variant rs9939609 is modestly associated with BMI and waist circumference, but not with energy intake or physical activity. Moreover, these effects were similar for EAs and AAs. Improved understanding of the effect of the FTO variant will offer new insights into the etiology of excess adiposity.


Serum monokine induced by gamma interferon as a novel biomarker for coronary artery calcification in humans.
T-cell-mediated immune responses play important roles in the progression of atherosclerotic disease. Studies have linked various inflammatory biomarkers with the burden of coronary artery calcification, but the significance of T-cell-specific chemokines in coronary artery calcification has not been confirmed. We aimed to examine the association between serum levels of the monokine induced by gamma interferon (MIG) and the coronary artery calcium score (CACS). We enrolled 456 individuals (285 men, 66.5±5.8 years) who were registered in the Mapo-gu public health center cohort. We selected 228 individuals with a CACS of more than 100 and 228 age-matched and sex-matched individuals with a CACS of less than 100. All participants underwent coronary computed tomography for CACS measuring. Clinical and laboratory variables including serum MIG levels were analyzed at the time of enrollment. The serum level of MIG was significantly higher in participants with a CACS of more than 100 (152.1±119.1 vs. 130.3±112.9, P=0.046). Serum MIG levels correlated significantly with CACS (r=0.113, P=0.016), and higher levels of MIG were associated with severe plaque burden (CACS>400, P=0.025). Multiple linear regression analysis showed that serum MIG levels were associated independently with CACS after controlling for confounding factors and medications (β=0.114, P=0.026). Serum MIG levels were associated independently with CACS after adjusting for traditional cardiovascular risk factors. These findings suggest that MIG may be used as a novel biomarker for T-cell inflammation and atherosclerotic plaque burden in humans.


Guidelines for establishing a telemental health program to provide evidence-based therapy for trauma-exposed children and families.
Although similar rates of traumatic experiences exist in both rural and urban settings, mental health resources available to those living in rural areas are often scarce. Limited resources pose a problem for children and families living in rural areas, and several barriers to service access and utilization exist including reduced anonymity, few "after hours" services, decreased availability of evidence-based treatments, few specialty clinics, and expenses associated with travel, taking time off work, and provision of childcare. As a solution, the authors discuss the utility, use, and set-up of a telemental health program within an existing community outreach program. Suggestions for establishing a telemental health clinic are presented along with guidelines for the delivery of trauma-focused, cognitive-behavioral therapy (TF-CBT) via telemental health videoconferencing technology. Specific guidelines discussed include (1) establishing and using community partnerships, (2) Memoranda of Understanding (MOU), (3) equipment setup and technological resources, (4) videoconferencing software, (5) physical setup, (6) clinic administration, (7) service reimbursement and start-up costs, (8) therapy delivery modifications, and (9) delivering culturally competent services to rural and remote areas.


Unexpected brain finding in pre-autopsy postmortem CT.
A case is presented in which pre-autopsy postmortem computed tomography (PMCT) revealed an unexpected brain abscess with a related frontal sinusitis and an erosion of the posterior wall of the frontal sinus. PMCT findings enabled the forensic pathologists to adapt protective measures during autopsy and protect their health from infection. Pre-autopsy PMCT has been also useful in the early differential diagnosis procedure. The complementary use of postmortem imaging and autopsy can improve the quality of forensic death investigations.


How to write a great business plan.
Every seasoned investor knows that detailed financial projections for a new company are an act of imagination. Nevertheless, most business plans pour far too much ink on the numbers - and far too little on the information that really matters. Why? William Sahlman suggests that a great business plan is one that focuses on a series of questions. These questions relate to the four factors critical to the success of every new venture: the people, the opportunity, the context, and the possibilities for both risk and reward. The questions about people revolve around three issues: What do they know? Whom do they know? and How well are they known? As for opportunity, the plan should focus on two questions: Is the market for the venture's product or service large or rapidly growing (or preferably both)? and Is the industry structurally attractive? Then, in addition to demonstrating an understanding of the context in which their venture will operate, entrepreneurs should make clear how they will respond when that context inevitably changes. Finally, the plan should look unflinchingly at the risks the new venture faces, giving would-be backers a realistic idea of what magnitude of reward they can expect and when they can expect it. A great business plan is not easy to compose, Sahlman acknowledges, largely because most entrepreneurs are wild-eyed optimists. But one that asks the right questions is a powerful tool. A better deal, not to mention a better shot at success, awaits entrepreneurs who use it.


The role of preoperative breast magnetic resonance (MR) imaging for surgical decision in patients with triple-negative breast cancer.
Several reliable randomized studies do not recommend routine preoperative breast MR imaging for patients with breast cancer. However, because the principle of MR imaging is based on the dynamics of contrast enhancement, a specific biologic subgroup of tumors should sensitively respond to the imaging process. From 2008 to 2013, 918 eligible patients with breast cancer underwent breast surgery and were divided into two groups based on preoperative breast MR findings: patients in whom the surgical plan was changed and those in whom the surgical plan remained unchanged. We investigated the changing patterns of breast surgery based on routine mammography, ultrasound, and preoperative breast magnetic resonance (MR) findings and analyzed the association between additional suspicious lesions on breast MR imaging and clinicopathologic factors. Additional suspicious breast lesions were detected on preoperative MR imaging in 104 cases (11.3%), and the surgical strategy was changed as the final decision in 97 cases (10.6%). There was no difference between oncologic results between two groups. However, the triple-negative breast cancer (TNBC) was significantly associated with changing of the surgical strategy based on breast MR findings (P = 0.048). Additional preoperative breast MR imaging may be helpful in surgical decision for patients with TNBC.


A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons.
The ubiquitin ligase anaphase-promoting complex (APC) recruits the coactivator Cdc20 to drive mitosis in cycling cells. However, the nonmitotic functions of Cdc20-APC have remained unexplored. We report that Cdc20-APC plays an essential role in dendrite morphogenesis in postmitotic neurons. Knockdown of Cdc20 in cerebellar slices and in postnatal rats in vivo profoundly impairs the formation of granule neuron dendrite arbors in the cerebellar cortex. Remarkably, Cdc20 is enriched at the centrosome in neurons, and the centrosomal localization is critical for Cdc20-dependent dendrite development. We also find that the centrosome-associated protein histone deacetylase 6 (HDAC6) promotes the polyubiquitination of Cdc20, stimulates the activity of centrosomal Cdc20-APC, and drives the differentiation of dendrites. These findings define a postmitotic function for Cdc20-APC in the morphogenesis of dendrites in the mammalian brain. The identification of a centrosomal Cdc20-APC ubiquitin signaling pathway holds important implications for diverse biological processes, including neuronal connectivity and plasticity.


Toxin production by Campylobacter spp.
Of all the virulence factors that were proposed for Campylobacter jejuni and related species to cause disease in humans, the discovery of toxin production was the most promising but led to a rather confusing and even disappointing stream of data. The discussion of whether proteinaceous exotoxins are relevant in disease remains open. One important reason for this lack of consensus is the anecdotal nature of the literature reports. To provide a basis for an unbiased opinion, this review compiles all described exotoxins, compares their reported properties, and provides a summary of animal model studies and clinical data. The toxins are divided into enterotoxins and cytotoxins and are sorted according to their biochemical properties. Since many Campylobacter toxins have been compared with toxins of other species, some key examples of the latter are also discussed. Future directions of toxin research that appear promising are defined.


Effects of quality improvement strategies for type 2 diabetes on glycemic control: a meta-regression analysis.
There have been numerous reports of interventions designed to improve the care of patients with diabetes, but the effectiveness of such interventions is unclear. To assess the impact on glycemic control of 11 distinct strategies for quality improvement (QI) in adults with type 2 diabetes. MEDLINE (1966-April 2006) and the Cochrane Collaboration's Effective Practice and Organisation of Care Group database, which covers multiple bibliographic databases. Eligible studies included randomized or quasi-randomized controlled trials and controlled before-after studies that evaluated a QI intervention targeting some aspect of clinician behavior or organizational change and reported changes in glycosylated hemoglobin (HbA1c) values. Postintervention difference in HbA1c values were estimated using a meta-regression model that included baseline glycemic control and other key intervention and study features as predictors. Fifty randomized controlled trials, 3 quasi-randomized trials, and 13 controlled before-after trials met all inclusion criteria. Across these 66 trials, interventions reduced HbA(1c) values by a mean of 0.42% (95% confidence interval [CI], 0.29%-0.54%) over a median of 13 months of follow-up. Trials with fewer patients than the median for all included trials reported significantly greater effects than did larger trials (0.61% vs 0.27%, P = .004), strongly suggesting publication bias. Trials with mean baseline HbA1c values of 8.0% or greater also reported significantly larger effects (0.54% vs 0.20%, P = .005). Adjusting for these effects, 2 of the 11 categories of QI strategies were associated with reductions in HbA(1c) values of at least 0.50%: team changes (0.67%; 95% CI, 0.43%-0.91%; n = 26 trials) and case management (0.52%; 95% CI, 0.31%-0.73%; n = 26 trials); these also represented the only 2 strategies conferring significant incremental reductions in HbA1c values. Interventions involving team changes reduced values by 0.33% more (95% CI, 0.12%-0.54%; P = .004) than those without this strategy, and those involving case management reduced values by 0.22% more (95% CI, 0.00%-0.44%; P = .04) than those without case management. Interventions in which nurse or pharmacist case managers could make medication adjustments without awaiting physician authorization reduced values by 0.80% (95% CI, 0.51%-1.10%), vs only 0.32% (95% CI, 0.14%-0.49%) for all other interventions (P = .002). Most QI strategies produced small to modest improvements in glycemic control. Team changes and case management showed more robust improvements, especially for interventions in which case managers could adjust medications without awaiting physician approval. Estimates of the effectiveness of other specific QI strategies may have been limited by difficulty in classifying complex interventions, insufficient numbers of studies, and publication bias.


A substantial prehistoric European ancestry amongst Ashkenazi maternal lineages.
The origins of Ashkenazi Jews remain highly controversial. Like Judaism, mitochondrial DNA is passed along the maternal line. Its variation in the Ashkenazim is highly distinctive, with four major and numerous minor founders. However, due to their rarity in the general population, these founders have been difficult to trace to a source. Here we show that all four major founders, ~40% of Ashkenazi mtDNA variation, have ancestry in prehistoric Europe, rather than the Near East or Caucasus. Furthermore, most of the remaining minor founders share a similar deep European ancestry. Thus the great majority of Ashkenazi maternal lineages were not brought from the Levant, as commonly supposed, nor recruited in the Caucasus, as sometimes suggested, but assimilated within Europe. These results point to a significant role for the conversion of women in the formation of Ashkenazi communities, and provide the foundation for a detailed reconstruction of Ashkenazi genealogical history.


[Comparative bacteriologic activity of norfloxacin, ofloxacin and pefloxacin against 320 Gram-negative bacilli resistant and non-resistant to nalidixic acid and cephalosporins].
Bacteriostatic and bactericidal effects of three fluoroquinolones, norfloxacin, ofloxacin and pefloxacin, against 320 strains of Gram-negative bacilli were studied in vitro. For nalidixic acid-susceptible Enterobacteriaceae, susceptibility or resistance to second or third generation cephalosporins has no significant bearing on the MIC 90 of each of the three antibiotics. This is not so of nalidixic acid-resistant strains. All E. coli and K. pneumoniae strains are susceptible to the three quinolones (MIC 90 less than 3 mg/1); MICs 90 are higher for E. cloacae and S. marcescens; Serratia strains in particular have an MIC 90 greater than 6 mg/1. Nalidixic acid-susceptible Acinetobacter strains can be eliminated by ofloxacin or pefloxacin, whereas norfloxacin has the greatest activity against P. aeruginosa. We conclude that when multiresistant bacteria emerge, testing of susceptibility to the three quinolones studied may be useful.


Expression of a cryptic secondary sigma factor gene unveils natural competence for DNA transformation in Staphylococcus aureus.
It has long been a question whether Staphylococcus aureus, a major human pathogen, is able to develop natural competence for transformation by DNA. We previously showed that a novel staphylococcal secondary sigma factor, SigH, was a likely key component for competence development, but the corresponding gene appeared to be cryptic as its expression could not be detected during growth under standard laboratory conditions. Here, we have uncovered two distinct mechanisms allowing activation of SigH production in a minor fraction of the bacterial cell population. The first is a chromosomal gene duplication rearrangement occurring spontaneously at a low frequency [≤10(-5)], generating expression of a new chimeric sigH gene. The second involves post-transcriptional regulation through an upstream inverted repeat sequence, effectively suppressing expression of the sigH gene. Importantly, we have demonstrated for the first time that S. aureus cells producing active SigH become competent for transformation by plasmid or chromosomal DNA, which requires the expression of SigH-controlled competence genes. Additionally, using DNA from the N315 MRSA strain, we successfully transferred the full length SCCmecII element through natural transformation to a methicillin-sensitive strain, conferring methicillin resistance to the resulting S. aureus transformants. Taken together, we propose a unique model for staphylococcal competence regulation by SigH that could help explain the acquisition of antibiotic resistance genes through horizontal gene transfer in this important pathogen.


Motoneuronal and muscle-selective removal of ALS-related misfolded proteins.
ALS (amyotrophic lateral sclerosis), a fatal motoneuron (motor neuron) disease, occurs in clinically indistinguishable sporadic (sALS) or familial (fALS) forms. Most fALS-related mutant proteins identified so far are prone to misfolding, and must be degraded in order to protect motoneurons from their toxicity. This process, mediated by molecular chaperones, requires proteasome or autophagic systems. Motoneurons are particularly sensitive to misfolded protein toxicity, but other cell types such as the muscle cells could also be affected. Muscle-restricted expression of the fALS protein mutSOD1 (mutant superoxide dismutase 1) induces muscle atrophy and motoneuron death. We found that several genes have an altered expression in muscles of transgenic ALS mice at different stages of disease. MyoD, myogenin, atrogin-1, TGFβ1 (transforming growth factor β1) and components of the cell response to proteotoxicity [HSPB8 (heat shock 22kDa protein 8), Bag3 (Bcl-2-associated athanogene 3) and p62] are all up-regulated by mutSOD1 in skeletal muscle. When we compared the potential mutSOD1 toxicity in motoneuron (NSC34) and muscle (C2C12) cells, we found that muscle ALS models possess much higher chymotryptic proteasome activity and autophagy power than motoneuron ALS models. As a result, mutSOD1 molecular behaviour was found to be very different. MutSOD1 clearance was found to be much higher in muscle than in motoneurons. MutSOD1 aggregated and impaired proteasomes only in motoneurons, which were particularly sensitive to superoxide-induced oxidative stress. Moreover, in muscle cells, mutSOD1 was found to be soluble even after proteasome inhibition. This effect could be associated with a higher mutSOD1 autophagic clearance. Therefore muscle cells seem to manage misfolded mutSOD1 more efficiently than motoneurons, thus mutSOD1 toxicity in muscle may not directly depend on aggregation.


Predicting acute ovarian failure in female survivors of childhood cancer: a cohort study in the Childhood Cancer Survivor Study (CCSS) and the St Jude Lifetime Cohort (SJLIFE).
Cancer treatment can cause gonadal impairment. Acute ovarian failure is defined as the permanent loss of ovarian function within 5 years of cancer diagnosis. We aimed to develop and validate risk prediction tools to provide accurate clinical guidance for paediatric patients with cancer. In this cohort study, prediction models of acute ovarian failure risk were developed using eligible female US and Canadian participants in the Childhood Cancer Survivor Study (CCSS) cohort and validated in the St Jude Lifetime Cohort (SJLIFE) Study. 5-year survivors from the CCSS cohort were included if they were at least 18 years old at their most recent follow-up and had complete treatment exposure and adequate menstrual history (including age at menarche, current menstrual status, age at last menstruation, and menopausal aetiology) information available. Participants in the SJLIFE cohort were at least 10-year survivors. Participants were excluded from the prediction analysis if they had an ovarian hormone deficiency, had missing exposure information, or had indeterminate ovarian status. The outcome of acute ovarian failure was defined as permanent loss of ovarian function within 5 years of cancer diagnosis or no menarche after cancer treatment by the age of 18 years. Logistic regression, random forest, and support vector machines were used as candidate methods to develop the risk prediction models in the CCSS cohort. Prediction performance was evaluated internally (in the CCSS cohort) and externally (in the SJLIFE cohort) using the areas under the receiver operating characteristic curve (AUC) and the precision-recall curve (average precision [AP; average positive predictive value]). Data from the CCSS cohort were collected for participants followed up between Nov 3, 1992, and Nov 25, 2016, and from the SJLIFE cohort for participants followed up between Oct 17, 2007, and April 16, 2012. Of 11 336 female CCSS participants, 5886 (51·9%) met all inclusion criteria for analysis. 1644 participants were identified from the SJLIFE cohort, of whom 875 (53·2%) were eligible for analysis. 353 (6·0%) of analysed CCSS participants and 50 (5·7%) of analysed SJLIFE participants had acute ovarian failure. The overall median follow-up for the CCSS cohort was 23·9 years (IQR 20·4-27·9), and for SJLIFE it was 23·9 years (19·0-30·0). The three candidate methods (logistic regression, random forest, and support vector machines) yielded similar results, and a prescribed dose model with abdominal and pelvic radiation doses and an ovarian dose model with ovarian radiation dosimetry using logistic regression were selected. Common predictors in both models were history of haematopoietic stem-cell transplantation, cumulative alkylating drug dose, and an interaction between age at cancer diagnosis and haematopoietic stem-cell transplant. External validation of the model in the SJLIFE cohort produced an estimated AUC of 0·94 (95% CI 0·90-0·98) and AP of 0·68 (95% CI 0·53-0·81) for the ovarian dose model, and AUC of 0·96 (0·94-0·97) and AP of 0·46 (0·34-0·61) for the prescribed dose model. Based on these models, an online risk calculator has been developed for clinical use. Both acute ovarian failure risk prediction models performed well. The ovarian dose model is preferred if ovarian radiation dosimetry is available. The models, along with the online risk calculator, could help clinical discussions regarding the need for fertility preservation interventions in girls and young women newly diagnosed with cancer. Canadian Institutes of Health Research, Women and Children's Health Research Institute, National Cancer Institute, and American Lebanese Syrian Associated Charities.


Eclampsia.
Emergency medicine residents. Eclampsia is the development of a generalized seizure in pregnant patients with hypertension of pregnancy.1 Eclampsia exists on the spectrum of hypertension-related disorders in pregnancy, occurs in 1 out of 1,000-10,000 deliveries,1-3and is associated with significant maternal and fetal morbidity and mortality.4 Given the emergent nature of eclampsia and the benefit of rapid treatment, emergency medicine (EM) physicians need to quickly recognize and treat this rare pathology. Although residents have three to four years before becoming an attending, not all emergent pathologies may present clinically during their training. It is important to simulate rare, treatable conditions such as eclampsia to give learners exposure confidence in managing this disease. By the end of this simulation session, learners will be able to:Demonstrate care of a gravid patient with altered mental statusDemonstrate care of a gravid patient with seizuresRecognize care involved in assessment of fetal statusExecute appropriate subspecialty consultationRecognize the clinical signs and symptoms of eclampsiaDistinguish different treatment options for eclampsiaIdentify magnesium toxicity and reversal agentDifferentiate the spectrum of preeclampsia. As an educational strategy, simulation allows learners to partake in experiential learning. By creating a safe and supportive learning environment, simulation allows learners to facilitate deliberate practice and transfer learning in debriefing sessions. High-fidelity sessions involve software and technology to mimic realistic patient environments, which also activate learners' affective states to aid in decision-making abilities in complex medical cases.This session was conducted using a high-fidelity mannequin, SimMom (Laerdal), and a controlling Laerdal LLEAP Software. Faculty-led debriefing followed the simulation case and included discussion regarding presentation, spectrum, and management of the obstetrical emergency.5. Resident participants completed an evaluation form consisting of questions on a 5-point Likert scale assessing the realism and usefulness of the simulation. All 18 residents who participated in the simulation completed an evaluation form, and all agreed or strongly agreed the case was realistic and useful. Incorporating high-stakes, low-frequency presentations through simulation can be readily applied in residency education and well-received by residents. Increasing the difficulty through adjusting the clinical history and exam may challenge learners further. Medical simulation, eclampsia, pregnancy, obstetrics, emergency medicine.


First Report of Leifsonia xyli subsp. xyli, Causal Agent of Ratoon Stunting of Sugarcane, in Jamaica.
To our knowledge, this is the first report that Leifsonia xyli subsp. xyli, previously named Clavibacter xyli subsp. xyli (2), has been detected and identified in sugarcane in Jamaica. Although ratoon stunting (also known as ratoon stunting disease or RSD) has been reported in Jamaica since 1961, presence of the pathogen had never been confirmed in symptomatic tissues. A major industry-wide survey conducted in 1987 using the fluorescent antibody staining technique failed to detect positives in any of the 61 fields sampled in Jamaica. A new survey was conducted in 2004 on eight estates and the Sugar Industry Research Institute (SIRI) in Jamaica. Six arbitrarily selected stalks were sampled from each of 64 fields representing 25 different sugarcane cultivars. A 1-cm diameter core was extracted from the center of the bottom part of the stalk and used to detect the pathogen by tissue blot immunoassay (TBIA) (3). L. xyli subsp. xyli was detected in 26 of 384 samples (7%). At least one positive sample was found in 10 fields and seven cultivars and in one case (sugarcane cv. D14146 at the St Thomas Sugar Estate), all six stalks sampled in a field were positive. The highest number of infected fields (6 of 10) occurred at Worthy Park where cane yield in 2004 was 86.54 tons per ha compared with an average of 68.04 tons per ha for major estates in Jamaica (1). This latter result would indicate that where good quality agronomic practices are maintained, the effect of ratoon stunting might not be substantial or that sugarcane cultivars grown at this location were resistant to ratoon stunting. Pathogen identification was confirmed using nested polymerase chain reaction (PCR) with three samples from a TBIA-positive field of cv. D14146. Primary primers were RSD 33 (CTGGCACCCTGTGTTGTTTTC) and RSD 297 (TTCGGTTCTCATCTCAGCGTC) and secondary, nested primers were RST60 (TCAACGCAGAGATTGTCCAG) and RST59 (CGTCTTGAAGACACAGCGATGAG). The thermocycler parameters were denaturization at 94°C for 4 min, 31 cycles at 94°C for 30 s, 55°C for 30 s, 65°C for 1 min, and final extension at 65°C for 3 min. The nested-PCR product (approximately 230 bp) of each sample was cloned and sequenced. It showed 99 to 100% identity with the 16S-23S intergenic spacer region of L. xyli subsp. xyli, thus confirming occurrence of ratoon stunting in Jamaica. Since this study, the SIRI has installed a hot-water treatment plant and will heat-treat cuttings before planting the nurseries with new sugarcane clones selected for release to growers. The SIRI will also conduct screening for ratoon stunting resistance to ensure that susceptible clones are not released to the industry. Meanwhile, the SIRI will do a more intense survey so that a more comprehensive picture may be obtained of the presence of ratoon stunting in Jamaica. References: (1) Anonymous. Annual Report of the Sugar Industry Research Institute, Jamaica, 2004. (2) L. I. Evtushenko et al. Int. J. Syst. Evol. Microbiol. 50:371, 2000. (3) N. A. Harrison and M. J. Davis. Phytopathology 78:722, 1988.


The Myriapoda of Halimun-Salak National Park (Java, Indonesia): overview and faunal composition.
The myriapod fauna of the mega-diverse country of Indonesia is so far insufficiently known, with no species lists or determination keys. In order to obtain an overview of the faunal composition of the Myriapoda in an Indonesian forest system, the fauna of the Halimun-Salak National Park in western Java was explored during the dry season (September-October 2015) in the framework of the German-Indonesian INDOBIOSYS project (Indonesian Biodiversity Discovery and Information System). A total of 980 Myriapoda specimens were collected by hand by 3-4 researchers from three different sites in the national park, from which 796 specimens were determined to a higher taxonomic level (class, order, family) and 617 specimens were determined to morphospecies. Among these, 27 were Symphyla (4%) (excluded from further analyses), 226 Chilopoda (28%) and 543 Diplopoda (68%). The Scolopendromorpha (64% of all identified centipedes) and Polydesmida (69% of all identified Diplopoda) were the most represented orders in our samples. Twenty-four morphospecies of Chilopoda were determined: one each of Scutigeromorpha and Lithobiomorpha, six Scolopendromorpha and sixteen Geophilomorpha. Nine orders of diplopods were present, with a total of 47 morphospecies: one each of Polyxenida, Glomeridesmida and Chordeumatida, two each of Glomerida, Spirobolida and Siphonophorida, seven of Sphaerotheriida, ten of Spirostreptida and 21 of Polydesmida. Two species curves were obtained to have a first idea about the myriapod diversity in the Halimun-Salak National Park and to compare the three individual collecting sites. Our results depict the Scolopendromorpha as the most common centipedes in Javanese rainforests and the Geophilomorpha as the most species-rich order. In contrast, the Polydesmida were the most dominant millipede group with 167 specimens and with 13 morphospecies the family Paradoxosomatidae was the most diverse.


The mental diseases hospital, Singapore (1st 100 years)--a short history (Part II).
This article (in four parts) traces the history of the first four Mental Hospitals built in Singapore, which were occupied in 1840, 1861, 1887 and 1928. The management of the patients is described; also their lives and deaths. Mention is also made of the doctors and others who looked after them.


The subtalar joint complex of Australopithecus sediba.
The hominin talus has figured prominently in previous studies of the functional morphology of the talocrural joint, but the talocalcaneal and talonavicular joints have received comparatively less attention despite their functional importance as components of the subtalar joint complex. An associated complete talus and calcaneus attributed to the Malapa Hominin 2 (MH2) individual of Australopithecus sediba offers the opportunity to evaluate the subtalar joint complex in an early hominin. Furthermore, detailed morphological comparisons of A. sediba to other fossil hominins such as Australopithecus africanus have not yet been conducted. Here I quantify joint curvatures and angular measurements among extant hominoids and fossil hominins to evaluate the functional morphology of the subtalar joint complex of A. sediba. Australopithecus sediba uniquely combines talocalcaneal joint morphology indicative of mobility with specializations of the talonavicular joint that provide medial midtarsal stabilization. Multivariate analyses of talus and calcaneus variables show that A. sediba is most similar to extant gorillas in the morphology of the subtalar joint complex. In contrast, other hominins, such as OH 8, are more similar to modern humans. The morphological similarity between MH2 (U.W. 88-98/99) and specimens from Sterkfontein, Member 4 (StW 88, StW 102, StW 352) in morphologies of the talonavicular and talocalcaneal joints suggests that A. sediba may have possessed a foot that was functionally similar to that of A. africanus. This combination of morphologies in the A. sediba foot is probably derived among hominins and suggests that arboreality may have been adaptively significant for southern African Australopithecus.


Cardiac Steatosis in HIV-A Marker or Mediator of Disease?
Although people living with HIV (PLHIV) are approaching normal life expectancy, a limitation to achieving this goal is managing the higher prevalence of co-morbidities, including cardiovascular disease. Whilst ischaemic heart disease likely contributes to a large proportion of cardiac disease in the modern era of treatment, cardio-metabolic disease, including cardiac steatosis, akin to obesity-related heart disease, is also a possible mechanism of increased cardiac morbidity and mortality. HIV and other metabolic and inflammatory diseases affecting the heart, including obesity, share many cardio-metabolic abnormalities, with increased pericardial and myocardial fat content, in association with chronic systemic inflammatory changes and alterations in cardiac metabolism. Understanding the mechanisms of HIV-associated cardiac steatosis remains an important challenge, as managing the untreated metabolic and inflammatory precipitants may substantially improve cardiac outcomes for PLHIV.