Distorted perceptions of competence and incompetence are more than regression effects.
Students inaccurately assess their own skills, especially high- or low-performers on exams. This study assessed whether regression effects account for this observation. After completing the Infection and Immunity course final exam (IIF), second year medical students (N = 143) estimated their performance on the IIF in terms of percent correct and percentile rank. Second year grade point averages (M2GPAs) were combined with the IIF results to form five subgroups: 1 = true-low (lowest third on both IIF and M2GPA, 2 = false-low (lowest third on IIF only), 3 = middle (neither lowest nor highest third on IIF), 4 = false-high (highest third on IIF only), 5 = true-high (highest third on IIF and M2GPA). The false-low and false-high groups were considered more susceptible to regression effects due to likely group misclassification. Differences between self-assessment and actual performance within each group and between the five groups were used to estimate what portion of observed differences is due to general tendencies versus regression effects. Results found that students accurately assessed their percent correct, but inaccurately assessed their percentile rank. No statistically significant differences existed between the true and false-low subgroups nor the true- and false-high subgroups. Percentages of mean differences suggest that while regression effects resulted in 50-75% over/under-estimates of scores by students who were misclassified, when they were merged with the true-low/high groups, they do not account for more than 14% of low performer over-estimates of their performance and high performer under-estimates of their performance. Accurate percent correct assessments and distorted percentile rank assessments are challenges in using instructional methods dependent on student self-assessments of their learning needs. Identifying and helping students with distorted perceptions of their test performances may be a key issue in such instructional approaches.


The use of serotype 1- and serotype 3-specific polymerase chain reaction for the detection of Marek's disease virus in chickens.
A serotype 1- and serotype 3-specific detection of Marek's disease virus (MDV) by polymerase chain reaction (PCR) was developed. The sensitivity of the method when applied to cell culture grown virus was comparable with that of cultivation. The method was applied to various tissue samples from chickens experimentally inoculated with serotype 1 or serotype 3 MDV.The serotype 1 strains CVI988 and RB-1B could be detected in feather follicle epithelium up to 56 and 84 days post-inoculation (p.i.), respectively, while the MDV-3 serotype was detected until 42 days p.i. The purpose of this study was to develop and evaluate a reliable and easy-to-handle method for surveillance of the occurrence of MDV in chicken flocks. We emphasize the development of a method, which can be applied to types of samples conveniently collected in the field, e.g. feather tips and blood samples. In addition, the PCR was applied to samples collected from four commercial table egg layer flocks of young stock or pullets vaccinated with either serotype 1 (CVI988) or serotype 3 (HVT) vaccine. These flocks had various clinical signs of Marek's disease. MDV-1 was detected in buffy-coat cells, spleen, liver, skin, feather tips and ovaries. The detection of MDV in feather tips appeared to be as sensitive as co-cultivation of buffy-coat cells, although an inhibiting factor was observed in extracts from feather tips of non-white chickens. This inhibition could be overcome in most extracts by applying a bovine serum albumen pretreatment. The PCR proved to be a convenient tool for the monitoring of MDV in the poultry population, and feather tips were the most convenient and sensitive samples.


Longitudinal monitoring of STAT3 phosphorylation and histologic outcome of tofacitinib therapy in patients with ulcerative colitis.
Tofacitinib is the first in class, pan-JAK inhibitor approved for ulcerative colitis (UC). Clinical efficacy has been shown, but long-term real-life endoscopic and histologic data are lacking. To investigate the effects of tofacitinib in patients with refractory UC focussing on endoscopic, histologic and molecular outcomes, including STAT3 phosphorylation (pSTAT3) detection in the spatial context of mucosal inflammation METHODS: We prospectively monitored 59 highly refractory patients (96.7% anti-TNF exposure, 91.7% vedolizumab exposure) initiating tofacitinib at two IBD referral centres and assessed outcome at the end of induction and after 48 weeks of therapy. Endoscopic improvement was defined as a Mayo endoscopic subscore ≤1, endoscopic and histologic remission as Mayo endoscopic subscore 0 and Nancy histologic score 0. Multiplex immunohistochemistry with multispectral imaging was used to assess pSTAT3. Endoscopic improvement was achieved by 24.4% and 30.5% of patients at weeks 8 and 48, respectively. Endoscopic and histologic remission rates were 11.1%, 23.7 and 16.7%, 21.4%, respectively. Endoscopic improvement at week 8 was significantly associated with treatment continuation in the long-term (72.7% vs 20.6%, p = 0.003). Although we observed a gradual decrease of mucosal pSTAT3 levels in both remitters and non-remitters (p < 0.05), no association with treatment outcome could be demonstrated. However, lamina propria pSTAT3 was significantly associated with the Nancy Histologic index (p = 0.004). Tofacitinib can induce and maintain endoscopic and histologic remission in up to one-quarter of highly refractory UC patients. Longitudinal monitoring of nuclear pSTAT3 in mucosal tissue compartments reflects distinctive on-target effects, independently of long-term treatment outcomes.


Identifying gaps in parental support for families of children with hypoplastic left heart syndrome.
The purpose of this study is to identify gaps in support for parents of children with Hypoplastic Left Heart Syndrome. Using a mixed-methods approach, the researchers first studied the parental and care team experience through interviews of Hypoplastic Left Heart Syndrome mothers and members of the inter-professional care team and then conducted an international survey of 690 Hypoplastic Left Heart Syndrome primary caregivers to validate the qualitative findings. Parental and care team interviews revealed three main gaps in parental support, including lack of open communication, unrealistic parental expectations, and unclear inter-professional team roles. Survey results found that parents whose children were diagnosed with Hypoplastic Left Heart Syndrome after birth indicated significant dissatisfaction with the care team's open communication and welcoming of feedback (p = 0.008). As parents progress through the stages of surgical intervention, they also indicate significant dissatisfaction with the care team's anticipation of parental emotional needs and provision of coping resources (p = 0.003). Parental support interventions should focus on providing resources to help parents cope, helping the care team model open communication, and welcoming feedback on the parental experience. Interventions should be piloted with parents who are in the later stages of the surgical intervention timeline or whose children were diagnosed after birth as they are the populations who perceived the least support within this study.


Suppression of Hepatic CYP3A4 Expression and Activity by 3-Methylcholanthrene in Humanized PXR-CAR-CYP3A4/3A7 Mice.
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that activate the aryl hydrocarbon receptor, thereby triggering a range of biologic responses, exemplified by the induction of CYP1A1 PAHs can also regulate the expression of members of the CYP3A subfamily, with reports of mainly suppressive effects on mouse hepatic Cyp3a11 expression, but paradoxically both inductive and suppressive effects on human hepatic CYP3A4 expression. Understanding the regulation of CYP3A4 expression by PAHs is important because of the widespread exposure of humans to these chemicals and the central role of the CYP3A4 enzyme in the metabolism of clinically important drugs and endogenous substances. The present study used 3-methylcholanthrene (MC) as a model PAH to characterize the in vivo regulation of CYP3A4 expression and activity in humanized pregnane X receptor-constitutive androstane receptor-CYP3A4/3A7 mice. Adult mice were treated by intraperitoneal injection with MC (80 mg/kg), or corn oil vehicle, and euthanized 24 or 72 hours later. As a positive control response, pronounced induction of hepatic Cyp1a1 by MC was confirmed at both time points in males and females at the mRNA, protein, and catalytic activity levels. Basal hepatic CYP3A4 expression and activity were significantly higher in female versus male mice. MC treatment suppressed hepatic CYP3A4 in female mice at 72 hours postdosing at the mRNA, protein, and catalytic activity levels. A similar response was observed in male mice, although the suppression of CYP3A4 protein levels did not achieve statistical significance. This mouse model will facilitate further studies of the mechanisms and consequences of CYP3A4 suppression by PAHs.


Unchain my heart: the scientific foundations of cardiac repair.
In humans, the biological limitations to cardiac regenerative growth create both a clinical imperative--to offset cell death in acute ischemic injury and chronic heart failure--and a clinical opportunity; that is, for using cells, genes, and proteins to rescue cardiac muscle cell number or in other ways promote more efficacious cardiac repair. Recent experimental studies and early-phase clinical trials lend credence to the visionary goal of enhancing cardiac repair as an achievable therapeutic target.


Changes in Performance on Common Return-to-Sport Tests During a Collegiate Women's Soccer Season: Implications for Baseline Testing.
Baseline testing of objective lower limb function may help clinicians make more informed return-to-sport (RTS) decisions in the event of an anterior cruciate ligament (ACL) injury. However, as these tests are based on physical performance, it is possible that they improve during the season as athletes get stronger and fitter. Hence, it may be difficult to ascertain the patient's preinjury status and have an accurate reference for comparison when determining readiness for RTS. The purpose of this study was to examine changes in common ACL RTS tests during a college soccer season to determine the most appropriate time to perform baseline testing. Hop test performance will improve across the season. Descriptive laboratory; prospective cohort. Level 4. A total of 31 women's soccer players from 1 NCAA Division I university agreed to participate this study. Participants performed 4 single-leg hop tests and the 505-agility test to measure cutting speed on 3 occasions: preseason (PRE), midseason (MID), and end-of-season (END). Performance on each test was compared across days to determine whether performance increased during the season. As a secondary analysis, limb symmetry index (LSI) was also compared across the season. A total of 23 participants (age, 19.7 ± 1.3 years; height, 1.69 ± 0.07 m; weight 60.9 ± 7.2 kg) completed all 3 testing sessions during the season. Performance during PRE was better than MID and END for all hop tests (all P < 0.01). LSI did not change during the season (P value range, 0.18-0.79). Performance on the hop tests was best during preseason and declined thereafter, which may be reflective of cumulative fatigue. Baseline testing of RTS tests performed during preseason may provide an accurate representation of an athlete's best abilities over the course of a collegiate soccer season. Preseason testing would also enable athletic trainers to acquire baseline data for all athletes before they are injured.


The effect of glutathione on development in wild carrot suspension cultures.
The role of reduced and oxidized glutathione in plant development was investigated using wild carrot suspension cultures. Concentrations of GSH are lower in developing than in proliferating carrot cultures. Addition of 0.3 mM buthionine sulfoximine (a glutathione synthesis inhibitor) to developing cultures decreased the cellular GSH levels and enhanced somatic embryogenesis while addition of 0.6 mM GSH increased the cellular GSH levels and inhibited embryogenesis. Additions of GSH and buthionine sulfoximine to developing cultures also indicated that buthionine sulfoximine is acting specifically to lower GSH levels and not through some nonspecific toxic effect. These results provide evidence that the levels of GSH are important in determining whether carrot cells develop into somatic embryos or grow proliferatively.


Enhanced piezoelectric and acoustic performances of poly(vinylidene fluoride-trifluoroethylene) films for hydroacoustic applications.
Concerning the study of flexible piezoelectric devices, both scholars and engineers propose that poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) shows more merits than oriented polyvinylidene fluoride (OPVDF) in terms of dielectric, piezoelectric, mechanic-electric, acoustic emission reception performances, etc. Thus, in this study, to clarify the differences between the two types of polymers on their ferroelectric and piezoelectric behaviors, we systematically investigated samples to analyze their molecular structures and phase structures, and to compare their dielectric properties and acoustic emission reception performances. It was found that the wedge effect of TrFE, P(VDF-TrFE), possesses higher regular β phase crystal grains, which are easier to order along the electric field and possess more ordered static charge distribution than that of OPVDF. Consequently, a considerable saturated electric polarization (Pm ∼ 15 μC cm-2 under 225 MV m-1), a large piezoelectric coefficient (d33 ∼ -21.5 pC N-1) and a low coercive electric field (Ec ∼ 50 MV m-1) were obtained in the P(VDF-TrFE) films. It is worth noting that P(VDF-TrFE) shows a more stable d33 piezoelectric response (up to 120 °C) than that of the OPVDF. Additionally, the P(VDF-TrFE) piezoelectric films exhibit a sensitive acoustic emission reception property at approximately 70 dB and an extensive response frequency range from 10 to 100 kHz. These combined properties demonstrate that P(VDF-TrFE) piezoelectric films are a promising material for flexible and easily shaped electronic devices, including hydroacoustic sensors, actuators, and energy transfer units.


[Electrophysiologial evaluation of ozone in treating of lumbar disc herniation with curving sheath-needle multi-direction rotating injection].
To compare electrophysiological changes in treating lumbar disc herniation (LDH) with ozone by curving sheath-needle multi-direction rotating injection (CSNMRI) and conventional injection method. From May 2005 to June 2009,100 patients with LDH were studied, included 68 males and 32 females, ranging in age from 25 to 58 years with an average of 44 years, in course of disease from 3 months to 8 years with an average of 8.8 months. All patients were numbered according to sequence of visit, and were completely randomly divided into group A and group B with DPS software, 50 cases in each group. All patients were injected ozone into lesion of intervertebral disc, in group A with CSNMRI and in group B with conventional method. The electrophysiologic study of all patients was performed respectively before treatment and at the 3 month after treatment. The electromyogram (EMG) of the main muscle groups of involved lower limb and the corresponding segments of sacrospinal muscle was tested; the duration and multiphase-wave rate of MUP were calculated. H-reflex of tibial nerve in both lower limbs was observed and the number of abnormal H-reflex and the H-wave latency were recorded. After treatment, the number of muscles with abnormal EMG was reduced to different degrees in each group, but there was more significant reduction in group A (P < 0.05 or 0.01); the duration and multiphase-wave rate of MUP in the two groups were both reduced and close to the normal level (P < 0.01), yet the changes in group A was more than that of group B (P < 0.05 or 0.01). There was no significant difference in the number of abnormal H-reflex before treatment between two groups, whereas was markedly lower in group A than that of group B after treatment (P < 0.05). After treatment, H-wave latency in two groups was shortened and become close to normal, but group B was more statistically significant than group B (P < 0.05). The neural electrophysiological abnormalities can reflect the degree of nerve root compression and damage, and is one of the objective indicators to estimate neuromuscular function. It can better meliorate abnormal electrophysiology to inject ozone to treat LDH with CSNMRI than conventional method.


First report of Angiostrongylus vasorum and Hepatozoon from a red fox (Vulpes vulpes) from West Virginia, USA.
Angiostrongylus vasorum was identified in the lungs of a red fox (Vulpes vulpes) from West Virginia, United States (US), indicating a new geographical location for this metastrongylid nematode. The fox was euthanized and submitted for necropsy after displaying erratic behavior. We did not detect rabies virus or canine distemper virus from the fox. We observed bronchopneumonia associated with A. vasorum infection disseminated in both lungs. In addition, protozoal meronts were observed in the liver, spleen, and mesenteric lymph node, and were identified as Hepatozoon canis. Lymphoid depletion was also observed in the spleen and mesenteric lymph node. In addition to A. vasorum and H. canis infections, Eucoleus aerophilus eggs and adult worms were observed in the lungs of the fox. Severe lesions associated with A. vasorum infection were observed in the lungs and these were determined to be the likely cause of morbidity; however, synergistic effects among the multiple infections detected in this fox cannot be ruled out. This is the first report of an autochthonous A. vasorum infection in the US and from outside of Newfoundland Canada, the only place in North America where the parasite is known to be endemic. Additionally, this is the first report of a H. canis infection in a red fox from the US.


Iridium(I) N-heterocyclic carbene complexes of benzimidazol-2-ylidene: effect of electron donating groups on the catalytic transfer hydrogenation reaction.
Two new [Ir(NHC)(COD)Cl] (NHC = N-heterocyclic carbene; COD = 1,5-cyclooctadiene) iridium complexes (2a,b) have been prepared by the reaction of [Ir(COD)Cl]2 with in situ prepared NHC-Ag carbene transfer agents in dichloromethane at ambient temperature. They have been fully characterized by (1)H, (13)C NMR, and elemental analysis. X-ray diffraction studies on single crystals of 2a and 2b confirm the square planar geometry. Complexes of type [Ir(NHC)(CO)2Cl] [NHC = 1,3-diisopropyl(5,6-dimethyl)benzimidazol-2-ylidene] 3 were also synthesized to compare σ-donor/π-acceptor strength of NHC ligands. Transfer hydrogenation (TH) reactions of various aldehydes and ketones have been studied using complexes 2a and 2b as catalysts. The 5,6-dimethyl substituted iridium complex (2b) showed the highest catalytic activity for the TH reaction.


Respiratory complex III is required to maintain complex I in mammalian mitochondria.
A puzzling observation in patients with oxidative phosphorylation (OXPHOS) deficiencies is the presence of combined enzyme complex defects associated with a genetic alteration in only one protein-coding gene. In particular, mutations in the mtDNA encoded cytochrome b gene are associated either with combined complex I+III deficiency or with only complex III deficiency. We have reproduced the combined complex I+III defect in mouse and human cultured cell models harboring cytochrome b mutations. In both, complex III assembly is impeded and causes a severe reduction in the amount of complex I, not observed when complex III activity was pharmacologically inhibited. Metabolic labeling in mouse cells revealed that complex I was assembled, although its stability was severely hampered. Conversely, complex III stability was not influenced by the absence of complex I. This structural dependence among complexes I and III was confirmed in a muscle biopsy of a patient harboring a nonsense cytochrome b mutation.


The potential impact of sperm encapsulation technology on the importance of timing of artificial insemination: a perspective in the light of published work.
To facilitate artificial insemination with encapsulated spermatozoa independently of oestrus, ways must be found to extend the life of spermatozoa at body temperature, and to devise encapsulation procedures which will allow progressive release of viable spermatozoa over several days. In the past, the most common approach to the preservation of semen has been the principle of reduced temperature. However, the research literature presents several promising clues to the resolution of these problems; these are reviewed, and new directions are identified and explored. The potential impact of a successful encapsulation technology is recognized as the driving force for implementing the novel research required.


Microbial catalysis in bioelectrochemical technologies: status quo, challenges and perspectives.
Over the past decade, microbial electrochemical technologies, originally developed from an interesting physiological phenomenon, have evolved from a rush of initiatives for sustainable bioelectricity generation to a multitude of specialized applications in very different areas. Genetic engineering of microbial biocatalysts for target bioelectrochemical applications like biosensing or bioremediation, as well as the discovery of entirely new bioelectrochemical processes such as microbial electrosynthesis of commodity chemicals, open up completely new possibilities. Where stands this technology today? And what are the general and specific challenges it faces not only scientifically but also for transition into commercial applications? This review intends to summarize the recent advances and provides a perspective on future developments.


Sulfonylurea-sensitive potassium current evoked by sodium-loading in rat midbrain dopamine neurons.
In Parkinson's disease, there is evidence of impaired mitochondrial function which reduces the capacity to synthesize ATP in dopamine neurons. This would be expected to reduce the activity of the sodium pump (Na+/K+ ATPase), causing increased intracellular levels of Na+. Patch pipettes were used to introduce Na+ (40 mM in pipette solutions) into dopamine neurons in the rat midbrain slice in order to study the electrophysiological effects of increased intracellular Na+. We found that intracellular Na+ loading evoked 100-300 pA of outward current (at -60 mV) and increased whole-cell conductance; these effects developed gradually during the first 10 min after rupture of the membrane patch. Extracellular Ba2+ reduced most of the outward current evoked by Na+ loading; this Ba(2+)-sensitive current reversed direction at the expected reversal potential for K+ (EK), and was also blocked by extracellular tetraethylammonium (30 mM) and intracellular Cs+ (which replaced K+ in pipette solutions). The sulfonylurea drugs glipizide (IC50 = 4.9 nM), tolbutamide (IC50 = 23 microM) and glibenclamide (1 microM) were as effective as 300 microM Ba2+ in reducing the K+ current evoked by Na+ loading. When recording with "control" pipettes containing 15 mM Na+, diazoxide (300 microM) increased chord conductance and evoked outward current at -60 mV, which also reversed direction near EK. Effects of diazoxide were blocked by glibenclamide (1 microM) or glipizide (300 nM). Diazoxide (300 microM) and baclofen (3 microM), which also evoked K(+)-mediated outward currents recorded with control pipettes, caused little additional increases in outward currents during Na+ loading. Raising ATP concentrations to 10 mM in pipette solutions failed to significantly reduce currents evoked by diazoxide or Na+ loading, suggesting that these currents may not be mediated by ATP-sensitive K+ channels. Finally, Na+ loading using pipettes containing Cs+ in place of K+ evoked a relatively small outward current (50-150 pA at -60 mV), which developed gradually over the first 10 min after rupturing the membrane patch. This current was reduced by dihydro-ouabain (3 microM) and a low extracellular concentration of K+ (0.5 mM instead of 2.5 mM), but was not affected by Ba2+. We conclude that intracellular Na+ loading evokes a current generated by Na+/K+ ATPase in addition to sulfonylurea-sensitive K+ current. This Na(+)-dependent K+ current is unusual in its sensitivity to sulfonylureas, and could protect dopamine neurons against toxic effects of intracellular Na+ accumulation.


Double pedicled nasoseptal flap for skull base repair after endoscopic expanded endonasal approach.
Expanded endonasal approach offers a spectacular corridor for skull base tumour resection but requires reliable multilayer reconstruction techniques with a vascularized nasoseptal flap. On the basis on our substantial experience of 136 patients operated on between January 2008 and January 2020, the double pedicled nasoseptal flap technique was developed for skull base repair. The technique is finely detailed. The nasal floor mucosa was preserved. CSF leakage occurred in 4% of patients. Double pedicled nasoseptal flap is a reproducible and efficient technique for skull base reconstruction after expanded endonasal approach and is associated with limited rhinological complications.


Cdk1-dependent phosphorylation of Iqg1 governs actomyosin ring assembly prior to cytokinesis.
Contraction of the actomyosin ring (AMR) provides the centripetal force that drives cytokinesis. In budding yeast (Saccharomyces cerevisiae), assembly and contraction of the AMR is coordinated with membrane deposition and septum formation at the bud neck. A central player in this process is Iqg1, which promotes recruitment of actin to the myosin ring and links AMR assembly with that of septum-forming components. We observed early actin recruitment in response to inhibition of cyclin-dependent kinase 1 (Cdk1) activity, and we find that the Cdk1-dependent phosphorylation state of Iqg1 is a determining factor in the timing of bud neck localization of both Iqg1 and actin, with both proteins accumulating prematurely in cells expressing nonphosphorylatable Iqg1 mutants. We also identified the primary septum regulator Hof1 as a binding partner of Iqg1, providing a regulatory link between the septation and contractile pathways that cooperate to complete cytokinesis.


Engineering hydrogels as extracellular matrix mimics.
Extracellular matrix (ECM) is a complex cellular environment consisting of proteins, proteoglycans, and other soluble molecules. ECM provides structural support to mammalian cells and a regulatory milieu with a variety of important cell functions, including assembling cells into various tissues and organs, regulating growth and cell-cell communication. Developing a tailored in vitro cell culture environment that mimics the intricate and organized nanoscale meshwork of native ECM is desirable. Recent studies have shown the potential of hydrogels to mimic native ECM. Such an engineered native-like ECM is more likely to provide cells with rational cues for diagnostic and therapeutic studies. The research for novel biomaterials has led to an extension of the scope and techniques used to fabricate biomimetic hydrogel scaffolds for tissue engineering and regenerative medicine applications. In this article, we detail the progress of the current state-of-the-art engineering methods to create cell-encapsulating hydrogel tissue constructs as well as their applications in in vitro models in biomedicine.


Evaluation of Cortical Brain Parenchyma by Diffusion and Perfusion MRI Before and After Chronic Subdural Hematoma Surgery.
To evaluate microcirculatory changes in neighboring parenchyma as a result of pressure due to chronic subdural hematoma (CSDH) in early and late periods after hematoma drainage. The subject group consisted of 25 patients who underwent CSDH drainage. Brain diffusion and perfusion magnetic resonance images (MRIs) were obtained preoperatively, and at 48 hours (early period) and 2 months (late period) postoperatively. Measurements were performed on 1 cm2 regions of interest (ROI) in the neighboring parenchymal tissue. The early postoperative diffusion values showed improvement compared to the preoperative values. The late postoperative values showed improvement compared to the preoperative and early postoperative values. The early postoperative perfusion values showed slight decline compared to the preoperative values. However, the late postoperative values showed improvement compared to the preoperative and early postoperative values. The fact that there was an increase in diffusion values from early to late postoperative periods, compared with the preoperative period, indicates that the beneficial effects of surgery increase over time. Brain perfusion was found to be slightly decreased in early postoperative period. Following CSDH drainage, neurological deteriorations are observed in some patients in the early postoperative periods; a slight impairment in perfusion may account for this. However, during the late postoperative period, perfusion was seen to recover prominently.


Firing patterns of gonadotropin-releasing hormone neurons are sculpted by their biologic state.
Gonadotropin-releasing hormone (GnRH) neurons form the final pathway for the central neuronal control of fertility. GnRH is released in pulses that vary in frequency in females, helping drive hormonal changes of the reproductive cycle. In the common fertility disorder polycystic ovary syndrome (PCOS), persistent high-frequency hormone release is associated with disrupted cycles. We investigated long- and short-term action potential patterns of GnRH neurons in brain slices before and after puberty in female control and prenatally androgenized (PNA) mice, which mimic aspects of PCOS. A Monte Carlo (MC) approach was used to randomize action potential interval order. Dataset distributions were analysed to assess (i) if organization persists in GnRH neuron activity in vitro, and (ii) to determine if any organization changes with development and/or PNA treatment. GnRH neurons in adult control, but not PNA, mice produce long-term patterns different from MC distributions. Short-term patterns differ from MC distributions before puberty but become absorbed into the distributions with maturation, and the distributions narrow. These maturational changes are blunted by PNA treatment. Firing patterns of GnRH neurons in brain slices thus maintain organization dictated at least in part by the biologic status of the source and are disrupted in models of disease.


Intra-arterial cisplatin and FUDR in advanced malignancies confined to the head and neck.
Twenty-seven patients with advanced malignancies confined to the head and neck region were treated with intra-arterial (IA) cisplatin and 5-fluorodeoxyuridine (FUDR) using implantable pumps or injection ports. Tumor histologies were: 16 squamous cell, one mucoepidermoid, one adenocarcinoma, one neuroendocrine, four adenoid cystic, two acinic cell, one fibrosarcoma, and one melanoma. All primaries originated from tissues in the head and neck area. Nineteen patients had received prior treatment, including chemotherapy in 13; eight were newly diagnosed. Responses in 26 evaluable patients were two complete (CR), ten partial (PR), six minor (MR), and eight progressions. The median duration of response was 5 months, with a range of 2 to 11 months. Sites of progression were within the infused volume in 13 patients and to uninfused local-regional or distant sites in eight. The response rate in the subset of 15 patients with squamous cell head and neck cancer was 47%. Toxicity in the 26 patients included stomatitis in 88%, nausea and vomiting in 64%, myelosuppression in 15%, and grade 1 nephrotoxicity in 1%. A regional advantage for IA cisplatin and FUDR can be calculated based on total body clearance rates (CLTB) for these agents and estimates of external carotid artery (ECA) blood flow. However, frequent progression of disease outside the infused volume to regional and distant sites limits the usefulness of this approach in recurrent disease patients.


Differential modification of interferon regulatory factor 3 following virus particle entry.
Viral infection elicits the activation of numerous cellular signal transduction pathways, leading to the induction of both innate and adaptive immune responses in the host. In particular, interferon regulatory factor 3 (IRF3) has been shown to be essential for the induction of an antiviral response. Current models suggest that virus replication causes phosphorylation of C-terminal serine and threonine residues on IRF3, leading to its dimerization and translocation to the nucleus, where it activates interferon. Upon entry of replication-deficient Newcastle disease virus (NDV) particles, however, we failed to detect IRF3 dimerization or hyperphosphorylation, despite robust interferon-stimulated gene (ISG) and antiviral state induction and confirmation by small interfering RNA knockdown that IRF3 is essential for this response. To further compare the effects of various viruses and their replication status on IRF3 activation and to determine the minimal posttranslational modification required for IRF3 activation, two-dimensional gel electrophoresis and native polyacrylamide gel electrophoresis were employed. However, we failed to identify a minimal posttranslational modification of IRF3 that correlated with downstream biological activity, and the extent of posttranslational modification observed on IRF3 did not correlate with the degree of subsequent ISG induction. Thus, current techniques used to detect IRF3 activation are insufficient to infer its role in mediating downstream biological response induction and should be utilized with caution.


Babinski response: stimulus and effector.
This is an electromyographic study of the activity in flexor and extensor muscles of the big toe in 22 patients with a Babinski sign and 49 controls, after mechanical or electrical stimulation of the sole. The results indicate: (1) the Babinski sign is mediated by the extensor hallucis longus (EHL), and not by the extensor hallucis brevis; (2) electrical stimuli may fail to activate the EHL in these patients, and conversely may evoke EHL reflexes in control subjects; (3) in skin reflexes, electrical and mechanical stimuli are not freely interchangeable.


An unconventional TOG domain is required for CLASP localization.
Cytoplasmic linker-associated proteins (CLASPs) form a conserved family of microtubule-associated proteins (MAPs) that maintain microtubules in a growing state by promoting rescue while suppressing catastrophe.1 CLASP function involves an ordered array of tumor overexpressed gene (TOG) domains and binding to multiple protein partners via a conserved C-terminal domain (CTD).2,3 In migrating cells, CLASPs concentrate at the cortex near focal adhesions as part of cortical microtubule stabilization complexes (CMSCs), via binding of their CTD to the focal adhesion protein PHLDB2/LL5β.4,5 Cortical CLASPs also stabilize a subset of microtubules, which stimulate focal adhesion turnover and generate a polarized microtubule network toward the leading edge of migrating cells. CLASPs are also recruited to the trans-Golgi network (TGN) via an interaction between their CTD and the Golgin protein GCC185.6 This allows microtubule growth toward the leading edge of migrating cells, which is required for Golgi organization, polarized intracellular transport, and cell motility.7 In dividing cells, CLASPs are essential at kinetochores for efficient chromosome segregation and anaphase spindle integrity.8,9 Both CENP-E and ASTRIN bind and target CLASPs to kinetochores,10,11 although the CLASP domain required for this interaction is not known. Despite its high evolutionary conservation, the CTD remains structurally uncharacterized. Here, we find that the CTD can be structurally modeled as a TOG domain. We identify a surface-exposed and conserved arginine residue essential for CLASP CTD interaction with partner proteins. Together, our results provide a structural mechanism by which the CLASP CTD directs diverse sub-cellular localizations throughout the cell cycle.


Curative Effect of Early Full Nursing Combined with Postdischarge Continuation Nursing on Patients after Craniocerebral Trauma.
Early full nursing helps patients with some dysfunctions speed up the reorganization of central nervous system functions and coordinate muscle and limb activities. Postdischarge continuation nursing for patients who have not fully recovered after being discharged from the hospital can transfer nursing work from the hospital to the family to meet their nursing needs. In this study, early full nursing combined with postdischarge continuation nursing was used for patients with traumatic brain injury to explore its efficacy and its impact on patients' motor function, quality of life, and complications. The results of the study show that the total effective rate of the observation group (95.92%) was higher than that of the control group (85.71%). At discharge and 1 month, 3 months, and 6 months after discharge, the upper limb Fugl-Meyer score, lower limb Fugl-Meyer score, ARAT score, FIM score, 4 dimensions of GQOLI-74 score, and Barthel index scores of the observation group were higher than those of the control group in the same period. The postoperative complication rate (10.20%) of the observation group was lower than that of the control group (26.53%). Early full nursing combined with postdischarge continuation nursing can improve the rehabilitation effect, effectively promote the recovery of motor function in patients with traumatic brain injury, improve the quality of life, and reduce postoperative complications.


Factors influencing the utilization of dental services in East Java, Indonesia.
Background: Despite high levels dental issues and insurance coverage in the East Java province Indonesia, the utilization of dental services is still low. This research aims to test whether certain individual-level sociodemographic, behavioural, and clinical characteristics influenced the current level of dental services utilization by East Java residents. Methods: A secondary analysis was undertaken using data on the East Java province from the Indonesian Basic Health Research 2013, which included 90,551 randomly selected respondents aged 5-100 years old. Socio-demographic characteristics (age, sex, education and residential location), dental behavior (tooth brushing habit), and clinical (dental) condition were self-reported through a questionnaire. Multivariable models were generated to estimate prevalence ratios (PR), and 95% confidence intervals (95% CI). Results: Prevalence of dental service utilization during the last 12 months in East Java province is only 9 %. Respondents 25-<50 years old showed the highest utilization of dental services. Being male, having lower education and living in a district (as opposed to municipalities) were indicators for having lower utilization of dental treatment (PR [95% CI] = 0.81 [0.79-0.84], PR [95% CI] = 0.89 [0.86-0.93] and PR [95% CI] = 0.91 [0.88-0.95], respectively). Respondents with poor tooth brushing habit showed lower utilization of dental services. Having teeth was associated with higher utilization of dental treatment (PR [95% CI] = 1.39 [1.16-1.66). Conclusions: Age, sex, education and residential location influence the utilization of dental services among Indonesia's East Java residents. Poor tooth brushing habits and being edentulous are also indicators of lesser utilization. These results call for urgent public health interventions to increase equitable dental care services utilization.


Wavelet analysis of electron-density maps.
The wavelet transform is a powerful technique in signal processing and image analysis and it is shown here that wavelet analysis of low-resolution electron-density maps has the potential to increase their resolution. Like Fourier analysis, wavelet analysis expresses the image (electron density) in terms of a set of orthogonal functions. In the case of the Fourier transform, these functions are sines and cosines and each one contributes to the whole of the image. In contrast, the wavelet functions (simply called wavelets) can be quite localized and may only contribute to a small part of the image. This gives control over the amount of detail added to the map as the resolution increases. The mathematical details are outlined and an algorithm which achieves a resolution increase from 10 to 7 A using a knowledge of the wavelet-coefficient histograms, electron-density histogram and the observed structure amplitudes is described. These histograms are calculated from the electron density of known structures, but it seems likely that the histograms can be predicted, just as electron-density histograms are at high resolution. The results show that the wavelet coefficients contain the information necessary to increase the resolution of electron-density maps.


[A Case of Rectal Cancer with Unresectable Liver Metastasis Responding to Rechallenge with FOLFIRI].
A 63-year-old man underwent low anterior resection for rectal cancer.A synchronous liver metastasis located in segment 8 was 12 cm in diameter and unresectable due to its proximity to the inferior vena cava(IVC).The postoperative pathological findings revealed a T3(SS), N0, M1(liver)Stage IV tumor, and wild type K-RAS was expressed.We chose FOLFIRI plus cetuximab(Cmab)for first-line chemotherapy.After 6 courses, we changed the molecular target drug from Cmab to bevacizumab( Bmab)because the liver metastasis remained unresectable.The patient had long-term stable disease(SD)for approximately 30 months with the FOLFIRI-based regimen.We then changed the regimen to mFOLFOX6 plus Bmab for second-line, Cmab for third-line, and trifluridine/tipiracil hydrochloride for fourth-line chemotherapy to treat progressive disease(PD).After treatment with these chemotherapies, the patient wished to continue treatment.We restarted FOLFIRI plus Bmab for fifth-line chemotherapy as his general condition was still good.Consequently, his tumor markers levels decreased with stabilization of the disease on CT scans, and he continued therapy for 6 months while maintaining a good quality of life.This case suggested that rechallenge with anti-cancer agents could be effective and improve the prognosis of colorectal cancer patients after using all key drugs.


Clinical value of the Treponema pallidum haemagglutination test.
In 1,129 patients attending the Department for Sexually Transmitted Diseases, the serum was examined by three screening tests (VDRL slide, RPCF, and TPHA) and twelve cases of syphilis (1 per cent. of patients attenting the clinic) were discovered. Six of these patients were considered to have latent syphilis (5 acquired, 1 congenital) and were detected only by the TPHA; all six cases were confirmed by the FTA-ABS, The TPHA failed to detect three of the remaining six cases (2 primary and 1 very early, the latter in a contact of a patient with primary syphilis). All six cases were, however, detected by the VDRL. In seven cases, the TPHA was positive in the absence of other evidence of present or previous syphilis. In these cases the FTA-ABS was also negative. The clinical application of the TPHA test in the detection of syphilis is discussed.


Visual Complaints and Eye Problems in Orchestral Musicians.
To study visual complaints and eye diseases among professional and amateur orchestral musicians in the Netherlands. In this observational study, members from professional and amateur symphony or wind orchestras were asked to complete a questionnaire collecting demographic data, musical, medical, and family history, and data on present visual complaints and/or eye diseases. Questions about playing in the orchestra were also asked. Data from 70 professionals and 48 amateurs showed that most musicians needed glasses or contact lenses for playing in the orchestra (61% of the professionals, 63% of the amateurs). A majority (66% of professionals, 71% of amateurs) had visited an ophthalmologist at least once during their lifetime, and 10% of the professionals and 23% of the amateurs were currently under treatment of an ophthalmologist. Visual complaints while playing in the orchestra were quite common and included poor lighting conditions, problems with reading small notes, blurred vision, tired eyes, and itching or burning eyes. Professional musicians especially reported adverse effects of eye complaints encountered in the orchestra for daily life; 35% got tired earlier and 33% felt that they could not adequately perform their tasks in the orchestra. The results show that visual complaints and eye problems probably are quite common among orchestral musicians and therefore warrant further interest and research.


The Oxytricha trifallax mitochondrial genome.
The Oxytricha trifallax mitochondrial genome contains the largest sequenced ciliate mitochondrial chromosome (~70 kb) plus a ~5-kb linear plasmid bearing mitochondrial telomeres. We identify two new ciliate split genes (rps3 and nad2) as well as four new mitochondrial genes (ribosomal small subunit protein genes: rps- 2, 7, 8, 10), previously undetected in ciliates due to their extreme divergence. The increased size of the Oxytricha mitochondrial genome relative to other ciliates is primarily a consequence of terminal expansions, rather than the retention of ancestral mitochondrial genes. Successive segmental duplications, visible in one of the two Oxytricha mitochondrial subterminal regions, appear to have contributed to the genome expansion. Consistent with pseudogene formation and decay, the subtermini possess shorter, more loosely packed open reading frames than the remainder of the genome. The mitochondrial plasmid shares a 251-bp region with 82% identity to the mitochondrial chromosome, suggesting that it most likely integrated into the chromosome at least once. This region on the chromosome is also close to the end of the most terminal member of a series of duplications, hinting at a possible association between the plasmid and the duplications. The presence of mitochondrial telomeres on the mitochondrial plasmid suggests that such plasmids may be a vehicle for lateral transfer of telomeric sequences between mitochondrial genomes. We conjecture that the extreme divergence observed in ciliate mitochondrial genomes may be due, in part, to repeated invasions by relatively error-prone DNA polymerase-bearing mobile elements.


Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib.
This prospective, phase II trial evaluated the efficacy and safety of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours (GISTs) after failure of at least imatinib and sunitinib. Patients received oral dovitinib, 500 mg once daily, for 5 consecutive days, followed by a 2-day rest, every 28 days. The primary endpoint was disease control rate (DCR; objective response+stable disease (SD)) at 24 weeks, assessed by computed tomography (CT) scan according to RECIST v1.0. Metabolic response was evaluated by positron emission tomography (PET)-CT scans performed at baseline and after 4 weeks of treatment. Between September 2011 and April 2012, 30 patients were enrolled. DCR at 24 weeks by RECIST v1.0 was 13% and one patient (3%) had a partial response. Based on the European Organization for Research and Treatment of Cancer PET response criteria, four patients (13%) had a metabolic partial response after 4 weeks of treatment. At a median follow-up of 8.3 months (range, 6.3-12.2 months), median progression-free survival (PFS) was 3.6 months (95% confidence interval (CI), 3.5-3.7 months) and median overall survival was 9.7 months (95% CI, 6.0-13.4 months). Metabolic progressive disease at Week 4 was significantly associated with shorter PFS (P=0.03). Grade 3/4 adverse events included asthenia (20%), neutropenia (13%), thrombocytopenia (10%), and hypertriglyceridaemia (10%). Most toxicities were manageable by dose modification. Dovitinib showed modest antitumour activity with manageable toxicities in heavily pretreated patients with advanced GISTs.


Fixed-pattern noise correction method based on improved moment matching for a TDI CMOS image sensor.
In this paper, an improved moment matching method based on a spatial correlation filter (SCF) and bilateral filter (BF) is proposed to correct the fixed-pattern noise (FPN) of a time-delay-integration CMOS image sensor (TDI-CIS). First, the values of row FPN (RFPN) and column FPN (CFPN) are estimated and added to the original image through SCF and BF, respectively. Then the filtered image will be processed by an improved moment matching method with a moving window. Experimental results based on a 128-stage TDI-CIS show that, after correcting the FPN in the image captured under uniform illumination, the standard deviation of row mean vector (SDRMV) decreases from 5.6761 LSB to 0.1948 LSB, while the standard deviation of the column mean vector (SDCMV) decreases from 15.2005 LSB to 13.1949LSB. In addition, for different images captured by different TDI-CISs, the average decrease of SDRMV and SDCMV is 5.4922/2.0357 LSB, respectively. Comparative experimental results indicate that the proposed method can effectively correct the FPNs of different TDI-CISs while maintaining image details without any auxiliary equipment.


The p97/VCP adaptor UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions.
p97, also known as valosin-containing protein, is an essential cytosolic AAA+ (ATPases associated with diverse cellular activities) hexamer that unfolds substrate polypeptides to support protein homeostasis and macromolecular disassembly. Distinct sets of p97 adaptors guide cellular functions but their roles in direct control of the hexamer are unclear. The UBXD1 adaptor localizes with p97 in critical mitochondria and lysosome clearance pathways and contains multiple p97-interacting domains. Here we identify UBXD1 as a potent p97 ATPase inhibitor and report structures of intact human p97-UBXD1 complexes that reveal extensive UBXD1 contacts across p97 and an asymmetric remodeling of the hexamer. Conserved VIM, UBX and PUB domains tether adjacent protomers while a connecting strand forms an N-terminal domain lariat with a helix wedged at the interprotomer interface. An additional VIM-connecting helix binds along the second (D2) AAA+ domain. Together, these contacts split the hexamer into a ring-open conformation. Structures, mutagenesis and comparisons to other adaptors further reveal how adaptors containing conserved p97-remodeling motifs regulate p97 ATPase activity and structure.


Setting the standard: multidisciplinary hallmarks for structural, equitable and tracked antibiotic policy.
There is increasing concern globally about the enormity of the threats posed by antimicrobial resistance (AMR) to human, animal, plant and environmental health. A proliferation of international, national and institutional reports on the problems posed by AMR and the need for antibiotic stewardship have galvanised attention on the global stage. However, the AMR community increasingly laments a lack of action, often identified as an 'implementation gap'. At a policy level, the design of internationally salient solutions that are able to address AMR's interconnected biological and social (historical, political, economic and cultural) dimensions is not straightforward. This multidisciplinary paper responds by asking two basic questions: (A) Is a universal approach to AMR policy and antibiotic stewardship possible? (B) If yes, what hallmarks characterise 'good' antibiotic policy? Our multistage analysis revealed four central challenges facing current international antibiotic policy: metrics, prioritisation, implementation and inequality. In response to this diagnosis, we propose three hallmarks that can support robust international antibiotic policy. Emerging hallmarks for good antibiotic policies are: Structural, Equitable and Tracked. We describe these hallmarks and propose their consideration should aid the design and evaluation of international antibiotic policies with maximal benefit at both local and international scales.


Theoretical analysis of divalent cation effects on aptamer recognition of neurotransmitter targets.
Aptamer-based sensing of small molecules such as dopamine and serotonin in the brain, requires characterization of the specific aptamer sequences in solutions mimicking the in vivo environment with physiological ionic concentrations. In particular, divalent cations (Mg2+ and Ca2+) present in brain fluid, have been shown to affect the conformational dynamics of aptamers upon target recognition. Thus, for biosensors that transduce aptamer structure switching as the signal response, it is critical to interrogate the influence of divalent cations on each unique aptamer sequence. Herein, we demonstrate the potential of molecular dynamics (MD) simulations to predict the behaviour of dopamine and serotonin aptamers on sensor surfaces. The simulations enable molecular-level visualization of aptamer conformational changes that, in some cases, are significantly influenced by divalent cations. The correlations of theoretical simulations with experimental findings validate the potential for MD simulations to predict aptamer-specific behaviors on biosensors.


Understanding the contribution of general medical services to acute inpatient care in Victorian public hospitals.
General medicine is an integral part of health services, yet there is little data highlighting their contribution to acute hospital care in Australia. To utilise the Victorian Department of Health's administrative dataset for hospital admissions to evaluate the relative contribution and trends over time of general medical services to acute multiday inpatient hospital separations in the Victorian public healthcare system. A retrospective time-series study of general medical activity compared to other major specialties using hospital-level data provided by the Department of Health: (i) extrapolation from diagnosis-related group (DRG) activity data (2011-2021) and, (ii) directly reported discharge unit-based activity (available from 2018). Acute multiday separations of all patients aged ≥18 years from all metropolitan and rural Victorian public hospitals were included. Using the DRG-based data, general medicine ranked as the largest care provider of all specialties studied, accounting for 12.1% of separations. Despite the largest increase at a rate of 2831 separations/year (0.336%/year of total, P < 0.001) compared to others, mean length of stay declined by 0.08 days/year (P < 0.001). These findings were significant for metropolitan and rural hospitals. The use of directly reported discharge unit-based data also ranked general medicine as the largest care provider accounting for 32.9% of total separations, with rural hospital general medical services contributing nearly 50% of all multiday separations. Both DRG-based data and discharge unit-based data indicate that general medicine is the largest provider of acute multiday inpatient care in Victorian hospitals. The estimate of contribution of general medicine differed between the two datasets as DRG data likely over-represents the role of other specialties possibly due to assumptions regarding specialty management of varying groups of diagnoses.


When a child dies: pediatric oncologists' follow-up practices with families after the death of their child.
Follow-up practices with bereaved families are considered a part of good medical care, yet little is known about pediatric oncologists' protocol with families when their patients die. The objective of this study was to examine follow-up practices employed by pediatric oncologists after patient death using an in-depth qualitative analysis. The Grounded Theory method of data collection and analysis was used. Twenty-one pediatric oncologists at two Canadian pediatric hospitals were interviewed about their follow-up practices with bereaved families after patients died. Line-by-line coding was used to establish codes and themes, and constant comparison was used to establish relationships among emerging codes and themes. Pediatric oncologists actively engage in follow-up practices that include making phone calls, sending an email or condolence card, attending funerals or visitations, having long-term and short-term meetings with parents, and attending hospital or departmental memorials for the deceased child. Attending funerals or visitations was less frequent and varied widely across pediatric oncologists. Reasons for not participating in bereavement follow-up practices included logistical, emotional, and practical considerations. While the majority of pediatric oncologists at two Canadian centers engage in some follow-up practices with bereaved families, these practices are complex and challenging because of the emotional nature of these interactions. Medical institutions should provide both structured time for this follow-up work with families, as well as medical education and financial and emotional support to pediatric oncologists who continue caring for these families long after their child has died.


Early administration of therapeutic anticoagulation following intravenous thrombolysis for acute cardiogenic embolic stroke caused by left ventricular thrombus: case report and topic review.
Cardiogenic cerebral embolism represents 20% of all acute ischemic strokes (AISs) with one-third of these being caused by left ventricular thrombus (LVT). LVT is not a contraindication for treatment with intravenous recombinant tissue plasminogen activator (IV rtPA) for AIS. However, the subsequent treatment of a potentially unstable LVT is contraindicated for 24 h following the use of IV rtPA according to current guidelines. We present a 66-year-old man with AIS treated with IV rtPA. Echocardiogram shortly after treatment demonstrated both a large apical and septal thrombus in the left ventricle and at 12 h post IV rtPA infusion, therapeutic anticoagulation with heparin was started without complication. In practice, the action of IV rtPA outlasts its apparent half-life because of thrombin-binding and the prolonged effects and longer half-life of its product, plasmin; however, the pharmacokinetics do not warrant prolonged avoidance of therapeutic anticoagulation when clinically indicated. Our case demonstrates that anticoagulation for potentially unstable LVT can be safely initiated at 12 h following IV rtPA treatment for AIS.


Preparing Medical Imaging Data for Machine Learning.
Artificial intelligence (AI) continues to garner substantial interest in medical imaging. The potential applications are vast and include the entirety of the medical imaging life cycle from image creation to diagnosis to outcome prediction. The chief obstacles to development and clinical implementation of AI algorithms include availability of sufficiently large, curated, and representative training data that includes expert labeling (eg, annotations). Current supervised AI methods require a curation process for data to optimally train, validate, and test algorithms. Currently, most research groups and industry have limited data access based on small sample sizes from small geographic areas. In addition, the preparation of data is a costly and time-intensive process, the results of which are algorithms with limited utility and poor generalization. In this article, the authors describe fundamental steps for preparing medical imaging data in AI algorithm development, explain current limitations to data curation, and explore new approaches to address the problem of data availability.


Primary pulmonary hypertension.
Primary Pulmonary Hypertension (PPH) is a rare disease that progressively increases pulmonary arterial pressure and pulmonary vascular resistance to the point of right heart failure, in the absence of secondary causes of the disease. The following specific risk factors that can trigger PPH have been identified and examined: appetite depressant drugs, oral contraceptives and hyperuricaemia. Familial PPH transmitted by an incomplete penetrance dominant autosomic mechanism is responsible for about 6% of PPH cases. Recent research groups have identified the gene responsible for familial PPH. Since pulmonary vasoconstriction is the prime cause of PPH, vasodilation of the pulmonary arterial circulation system (using prostacyclin in the form of epoprostenol or iloprost) is the main aim of treatment.


Comparison of two methods for detection of fecal indicator bacteria used in water quality monitoring of the Three Gorges Reservoir.
Scientifically sound methods to rapidly measure fecal indicator bacteria are important to ensure safe water for drinking and recreational purposes. A total of 200 water samples obtained from the Three Gorges Reservoir during three successive one-year study periods (October 2009 to September 2012) were analyzed using multiple-tube fermentation (MTF) and most probable numbers combined with polymerase chain reaction (MPN-PCR). The MPN-PCR method was found to be significantly more sensitive than the MTF method for detecting Escherichia coli and Enterococcus spp., and of equal sensitivity for detecting total coliforms when all surface water samples were grouped together. The two analytical methods had a strong, significant relationship, but MPN-PCR took only 12-18hr, compared with the 3-8days needed using the MTF method. Bacterial concentrations varied per sampling site but were significantly lower in the mainstream of the Yangtze River than those in the backwater areas of tributaries. The water quality of 85.8% of water samples from the mainstream was suitable for use as a centralized potable water source, while the water quality of 52.5% of water samples from the backwater areas was unsuitable for recreational activities. Relationships between fecal indicator bacteria showed significant correlation (r=0.636-0.909, p<0.01, n=200), while a weak but significant correlation was found between fecal indicators and water turbidity, water temperature, daily inflow, and total dissolved solids (r=0.237-0.532, p<0.05, n=200). The study indicated that MPN-PCR is a rapid and easily performed deoxyribonucleic acid (DNA)-based method for quantitative detection of viable total coliforms, E. coli, and Enterococcus spp. in surface water.


Mitofusin 2 inhibits bladder cancer cell proliferation and invasion via the Wnt/β-catenin pathway.
The present study aimed to investigate the biological role of the mitochondrial GTPase mitofusin-2 (MFN2) in bladder cancer. MFN2 mRNA expression in tumor and paired adjacent non-tumor tissues from 8 patients was investigated using reverse transcription-quantitative polymerase chain reaction analysis. Immunohistochemistry was used to investigate MFN2 expression in 117 bladder cancer specimens. The associations of MFN2 expression with clinicopathological parameters were evaluated statistically. In addition, the biological role of MFN2 in the proliferation, migration and invasion of bladder cancer cells was examined. It was identified that MFN2 expression was significantly downregulated in bladder cancer tissues compared with normal tissues. MFN2 expression was associated with tumor stage, tumor grade and lymph node status. Furthermore, patients with low MFN2 expression demonstrated a shorter overall survival time (P=0.025). MFN2 knockdown by small interfering RNA promoted cancer cell proliferation, migration and invasion in vitro, and enhanced tumor progression in vivo. Mechanistically, MFN2 was revealed to be involved in Wnt/β-catenin signaling. In conclusion, MFN2 may serve as a potential therapeutic target in the treatment of bladder cancer, and the progress of bladder cancer may be delayed by regulating MFN2 expression.


Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis.
Premature, very low birth weight (VLBW) neonates are at risk for early-onset sepsis and receive ampicillin and gentamicin post-birth. Antimicrobial stewardship supports short-course antibiotics, but how long antibiotic concentrations remain therapeutic post-last dose is unknown. Using Monte Carlo simulations (NONMEM 7.3), we analyzed antibiotic exposures in a retrospective cohort of 34 689 neonates (<1500 g, 22-27 weeks of gestation). Therapeutic exposure for ampicillin and gentamicin was evaluated relative to the minimum inhibitory concentration (MIC) for common pathogens (MIC 0.25-8 mcg/mL for group B streptococcus [GBS] and Escherichia coli). Post-discontinuation antibiotic exposure (PDAE) was defined as the time from the last dose to time when concentration decreased below MIC. Neonates had a median (range) gestational age of 26 (22-27) weeks and BW, 790 g (400-1497) . All ampicillin dosing regimens (50-100 mg/kg every 8-12 hours for 2-6 doses) achieved therapeutic exposures > MIC range. After the last dose, the PDAE mean (95% confidence interval [CI]) ranged from 34 to 50 hours (17-79) for E. coli (MIC 8) and 82 to 104 hours (95% CI: 39-122) for GBS (MIC 0.25); longer PDAE occurred with higher dose, shorter interval, and longer course. Short-course ampicillin (2 doses, 50 mg/kg every 12 hours) provided PDAE 34 hours for E. coli and 82 hours for GBS. Single-dose 5 mg/kg gentamicin provided PDAE > MIC 2 for 26 hours. In VLBW neonates, ampicillin exposure remains therapeutic long after the last dose. Short-course ampicillin provided therapeutic exposures throughout the typical blood culture incubation period.


Medical utilization patterns of migrant farm workers in Wayne County, New York.
A representative sample of 218 migrant farm workers was randomly drawn in Wayne County, NY, during the summer of 1982. Three distinct migrant groups were identified: immigrants, recent migrants, and long-term migrants. Medical utilization patterns, including physician visits and use of medical services in the community health center, were compared among the three migrant groups. The determinants of physician visits were examined in a multiple regression model. The focus was also placed on types of health problems for which medical treatment had been delayed, and the reasons for the delay were clearly identified. Furthermore, this study examined migrants' subjective assessment of quality of health care in the community. The results of this study indicate that the provision of comprehensive health programs, removal of structural barriers in the health delivery system, and a program of migrant health education are the necessary steps to alter the medical utilization behavior of migrant farm workers.


Modulation of gut perception in humans by spatial summation phenomena.
1. We have recently shown that perception of intestinal stimuli increases by spatial summation phenomena. Our aim was to determine in humans whether intestinal perception depends on (a) the length of gut stimulated, and (b) the distance between stimuli. 2. In a first series of studies, we compared perception of isobaric intestinal distensions applied over a 3 cm segment and a 36 cm segment by means of two separate barostats (n = 8). In a second series of studies we compared perception of intestinal distensions applied simultaneously by two balloons sited 3, 12 or 48 cm apart (n = 6). 3. Distension of the 36 cm segment induced significantly greater perception than distension of the 3 cm intestinal segment (discomfort perceived at 20 +/- 2 mmHg and 31 +/- 2 mmHg, respectively; P < 0.05). Perception of intestinal balloon distension increased when a second stimulus was simultaneously applied, independently of the distance between the two balloons (the discomfort thresholds were 30 +/- 11, 20 +/- 6 and 28 +/- 7% lower with simultaneous distensions 3, 12 and 48 cm apart, respectively). 4. We conclude that perception of intestinal distension is determined by the extension of the field of stimulation, and the summation effect is similar whether adjacent or distant fields are stimulated.


Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: a randomized, controlled trial.
To examine whether dose escalation of intramuscular (IM) methotrexate (MTX) up to 45 mg/week improves disease control in patients who have active rheumatoid arthritis (RA) despite receiving conventional doses (15 mg/week) of IM MTX, and to obtain preliminary data on patient tolerability and adverse effects of higher doses of IM MTX. Patients >18 years of age who had active RA, defined as a European League Against Rheumatism (EULAR) Disease Activity Score in 28 joints (DAS28) of >3.2, and who had received 15-20 mg/week of oral MTX for at least 2 months were switched (week 0) to 15 mg/week of IM MTX for 6 weeks. Patients whose DAS28 remained >3.2 at both week 4 and week 6 were randomized, in a double-blind manner, either to continue to receive 15 mg/week IM MTX with monthly placebo escalation or to receive escalating doses of IM MTX monthly up to 45 mg/week. The dose of MTX or placebo was escalated every 4 weeks if the DAS28 was >2.5. Safety assessments and determination of the DAS28 were performed every 2 weeks and monthly, respectively. Disease activity parameters from the American College of Rheumatology (ACR) core disease activity set and health status as recorded on the Medical Outcomes Study Short-Form 12 were determined at baseline (week 0) and final assessment (week 22). The primary outcome was the percentage of patients in each group achieving a target DAS28 of <3.2. Secondary outcomes comprised the percentage of patients whose DAS28 improved by >1.2, the percentage of patients achieving a 20% improvement in the ACR core disease activity measures (ACR20), and the percentage of patients achieving a good response, a moderate response, or no response in accordance with the EULAR response criteria. Sixty-four patients were eligible for entry and were switched from oral MTX to 15 mg/week IM MTX. At baseline, the mean +/- SD DAS28 was 5.6 +/- 0.88; after 6 weeks of IM MTX, the DAS28 had improved by a mean of 0.42 (95% confidence interval [95% CI] 0.15-0.69). At 6 weeks, 54 patients still had a DAS28 of >3.2 and were therefore eligible for randomization. By 22 weeks, 1 patient (3.7%) in each group achieved the primary outcome of a DAS28 <3.2 (95% CI for the difference between the groups -15% to +15%). Five patients (18.5%) in each group showed an improvement of >1.2 in the DAS28 (95% CI for the difference between the groups -18% to +18%). One patient (3.7%) in each group achieved an ACR20 response, but none achieved a good response as defined by the EULAR response criteria. One patient in each group had a serious adverse reaction; minor adverse reactions were more frequently reported in the dose escalation group. Switching from oral to parenteral MTX 15 mg/week results in a minor improvement in disease control. For patients with active RA receiving 15 mg/week IM MTX, increasing the dose up to 45 mg/week does not improve disease control. Higher doses of IM MTX were generally well tolerated and not associated with an increase in serious adverse reactions to the drug.


Male and Female Physician Suicidality: A Systematic Review and Meta-analysis.
Population-based findings on physician suicide are of great relevance because this is an important and understudied topic. To evaluate male and female physician suicide risks compared with the general population from 1980 to date and test whether there is a reduction of SMR in cohorts after 1980 compared with before 1980 via a meta-analysis, modeling studies, and a systematic review emphasizing physician suicide risk factors. This study uses studies retrieved from PubMed, Scielo, PsycINFO, and Lilacs for human studies published by October 3, 2019, using the search term "(((suicide) OR (self-harm) OR (suicidality)) AND ((physicians) OR (doctors)))." Databases were also searched from countries listed in articles selected for review. Data were also extracted from an existing article by other authors to facilitate comparisons of the pre-1980 suicide rate with the post-1980 changes. Original articles assessing male and/or female physician suicide were included; for the meta-analysis, only cohorts from 1980 to the present were included. The preregistered systematic review and meta-analysis followed Cochrane, PRISMA, and MOOSE guidelines. Data were extracted into standardized tables per a prespecified structured checklist, and quality scores were added. Heterogeneity was tested via Q test, I2, and τ2. For pooled effect estimates, we used random-effects models. The Begg and Egger tests, sensitivity analyses, and meta-regression were performed. Proportional mortality ratios were presented when SMR data could not be extracted. Suicide SMRs for male and female physicians from 1980 to the present and changes over time (before and after 1980). Of 7877 search results, 32 articles were included in the systematic review and 9 articles and data sets in the meta-analysis. Meta-analysis showed a significantly higher suicide SMR in female physicians compared with women in general (1.46 [95% CI, 1.02-1.91]) and a significantly lower suicide SMR in male physicians compared with men in general (0.67 [95% CI, 0.55-0.79]). Male and female physician SMRs significantly decreased after 1980 vs before 1980 (male physicians: SMR, -0.84 [95% CI, -1.26 to -0.42]; P < .001; female physicians: SMR, -1.96 [95% CI, -3.09 to -0.84]; P = .002). No evidence of publication bias was found. In this study, suicide SMR was found to be high in female physicians and low in male physicians since 1980 but also to have decreased over time in both groups. Physician suicides are multifactorial, and further research into these factors is critical.


A method for determining cell number in the undisturbed epithelium of the mouse lens.
The anterior face of the mouse lens is covered by a layer of epithelial cells. The epithelial cells serve a barrier function at the lens surface and as a progenitor population from which lens fiber cells, the predominant cell type of the lens, are derived. Decreased epithelial cell density is commonly observed during aging and cataract formation in humans and animal models and may contribute directly to tissue opacification. However, the loss of cells from the epithelium is often not easy to quantify, in part because the cells are arrayed across a near-spherical surface and, as a consequence, are difficult to image and count. Here, we describe a technique for determining epithelial cell number in the undisturbed lens of the mouse, a popular cataract model. The method utilizes orthographic projections of confocal images collected from the anterior and equatorial regions of the lens. The overlapping projections are brought into register using the unique distribution of proliferating cells as fiduciary points. Cell counts are performed using a computer-assisted method. This approach offers several advantages over flat-mount methods employed previously.


[Transfer of transformation and conjugation plasmids from Escherichia coli to Bacillus subtilis and Azospirillum brasilense].
The conjugative transfer of RP4 plasmid from Escherichia coli to Azospirillum brasilense was detected after introduction and subsequent incubation of these microorganisms in soil. The plasmid transfer via transformation from Escherichia coli to Bacillus subtilis was observed in case both bacteria were growing together in sand containing sucrose solution. The possible reason for low frequency interspecies plasmid transformation under conditions close to natural habitats is poor survival of "domesticated" rather than wild type Bacillus subtilis strains and lack of competence state in this case.


The effect of aromatherapy and massage administered in different ways to women with breast cancer on their symptoms and quality of life.
The primary objective of this study was to assess the effect of aromatherapy and classic massage administered in various ways to breast cancer patients on their symptoms and quality of life. The sampling consisted of 280 patients. Quality of life and symptoms of the patients were evaluated once at baseline and then at week 6 and week 10 following the intervention. After intervention, the control group was observed to have lower total quality of life score and subdomain scores, whereas fragrance, massage and aromatherapy massage groups had higher scores, and the increase was more obvious particularly in the patients in the aromatherapy massage group. Similarly, whereas psychological and physical symptoms were experienced more intensely in the control group, the severity of all the symptoms experienced by the other patients decreased at week 6 and week 10 as compared with baseline especially in the group that was administered massage with aromatherapy.


[Pentachlorophenol inhibition of succinate oxidation by the respiratory chain in submitochondrial particles from the bovine heart].
Study on the effect of pentachlorophenol on the succinate oxidase activity of submitochondrial particles and on the reduction level of cytochromes b revealed that the Ki value for PCP is equal to 2-4 microM. The succinate-DCPIP-reductase activity is noncompetitively inhibited with PCP (by 75-85%) (Ki = 3.6 microM). In the case of the succinate-PMS-reductase activity PCP at micromolar concentrations decreases the value of V only by 40% (C50 = 2 microM) with a simultaneous increase of the Km value for PMS. The identity of Ki values for PCP under these conditions suggests that the effect of PCP is due to the inhibitor interaction with the same component of the succinate dehydrogenase complex. The type of action of PCP on the succinate-acceptor-reductase activities indicates that the inhibiting effect of PCP on succinate oxidations is similar to that exerted by traditional inhibitors of succinate dehydrogenase--tenoyltrifluoroacetone and carboxins. Since PCP inhibits succinate dehydrogenase at low concentrations, it seems likely that the biological (pesticidal) effect of PCP is provided for not only by its uncoupling action but also by the inhibition of succinate oxidation in the respiratory chain.


Associations between spinal flexibility and bracing outcomes in adolescent idiopathic scoliosis: a literature review.
To identify the existing assessment methods used to measure the spinal flexibility of adolescents with idiopathic scoliosis before bracing and to evaluate the predictive effect of spinal flexibility on bracing outcomes. A broad literature search was performed in the PubMed, Web of Science, EMBASE, CINAHL, Scopus, and Cochrane Library databases to obtain relevant information about spinal flexibility and bracing outcomes. All literature was retrieved by October 14, 2023. The inclusion and exclusion criteria were meticulously determined. The quality of each included study and the level of evidence were evaluated by the Quality in Prognosis Studies (QUIPS) method and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system, respectively. After screening 1863 articles retrieved from databases, a total of 14 studies with 2261 subjects were eligible for the final analysis in this review. Overall, nine methods of flexibility assessment were identified, including supine radiographs, supine lateral bending radiographs, lateral bending radiographs but without clear positions, hanging radiographs, fulcrum bending physical method, and ultrasound imaging in the positions of supine, prone, sitting with side bending and prone with side bending. In addition, five studies demonstrated that flexibility had a strong correlation with in-brace correction, and eleven studies illustrated that spinal flexibility was a predictive factor of the bracing outcomes of initial in-brace Cobb angle, initial in-brace correction rate, curve progression, and curve regression. The results of GRADE demonstrated a moderate-evidence rating for the predictive value of spinal flexibility. Supine radiography was the most prevalent method for measuring spinal flexibility at the pre-brace stage. Spinal flexibility was strongly correlated with the in-brace Cobb angle or correction rate, and moderate evidence supported that spinal flexibility could predict bracing outcomes.


A case of anorexia nervosa with comorbid Crohn's disease: beneficial effects of anti-TNF-α therapy?
This case report describes a 26-year-old woman affected by long-lasting anorexia nervosa (AN) and Crohn's disease. Worsening of the bowel illness led to the prescription of immunosuppressive therapy (biologic infliximab for 4 months, followed by adalimumab for 6 months) and referral to our Eating Disorders Unit. Although she initially demonstrated denial of her eating disorder, in a few months she gradually improved her weight and psychopathology. Crohn's disease can worsen AN by modifying hunger and energy expenditure through the effects of TNF-α and IL-6, pro-inflammatory cytokines which moderate leptin and melanocortin signaling. Previous studies have observed the antidepressant effects of TNF antagonist in patients with treatment-resistant depression with high baseline inflammatory biomarkers. Our case report suggests that future studies are needed to clarify the existence, patterns, and extent of increased inflammatory markers in patients with AN, and whether they determine clinical features or identify subgroups of patients. Potential therapeutic significance of above issues remains to be determined.


Immunotactoid glomerulopathy is a rare entity with monoclonal and polyclonal variants.
Immunotactoid glomerulopathy (ITG) is a rare form of glomerulonephritis for which our understanding is limited to case reports and small case series. Herein we describe the clinical, pathologic, and outcome characteristics of 73 patients with ITG who typically presented with proteinuria, hematuria, and renal insufficiency. Hematologic disorders were present in 66% of patients, including lymphoma in 41% (mainly chronic lymphocytic leukemia/small lymphocytic lymphoma), monoclonal gammopathy in 20%, and multiple myeloma in 6%. Light microscopy revealed endocapillary proliferative (35%), membranoproliferative (29%) and membranous (29%) patterns of glomerular involvement. Electron microscopy revealed characteristic microtubular deposits with a diameter of 14-60 nm, hollow cores, frequent parallel alignment, and a predominant distribution outside of the lamina densa of the glomerular basement membrane. Importantly, immunofluorescence revealed IgG-dominant staining which was light chain and IgG subclass restricted in 67% of cases, indicating monoclonal composition. This finding was used to distinguish monoclonal and polyclonal variants of ITG. As compared to polyclonal, monoclonal ITG had a higher incidence of lymphoma (53% vs. 11%), multiple myeloma (8% vs. 0), and monoclonal gammopathy (22% vs. 16%). Monoclonal ITG was more commonly treated with clone-directed therapy, which was associated with more frequent remission and less frequent end stage kidney disease. Thus, a third of ITG cases are polyclonal but a quarter of these cases are associated with hematologic conditions, underscoring the need for hematologic evaluation in all patients with ITG. Hence, based on these distinctions, ITG should be subclassified into monoclonal and polyclonal variants. Prognosis of ITG is good if the underlying hematologic condition is treated.


Incidence and Factors Predictive of Dysphagia and Dysphonia After Anterior Operation With Multilevel Cervical Spondylotic Myelopathy.
Retrospective database analysis. The objective of the study was to quantify the incidence of dysphagia and dysphonia and assess the associated risk factors after multilevel cervical anterior operation. Anterior approach for multilevel cervical spondylotic myelopathy has been developed and obtained favorable outcomes. As number of fused levels increased, the operation difficulty, invasiveness and operative risks are higher. Meanwhile, the 2 most common postoperative complications described in the literature are dysphonia and dysphagia. Two hundred thirty-six multilevel cervical spondylotic myelopathy patients between October 2004 and June 2012 were included in the study. All patients undergoing anterior operation, and incidences of dysphagia were identified. Risk factors were assessed using logistic regression. At a minimum of 1 year after operation, 70.6% (n=156) were 3-level anterior operation and 29.4% (n=65) were 4-level anterior operation. The overall dysphagia rate was 23.1% (51 patients). The overall dysphonia rate was 28.5% (63 patients). Logistic regression analysis demonstrated that risk factors for dysphagia included age, operation time and lack of tracheal traction exercise. Age, operation time were 2 factors significantly related to dysphonia. The incidence of postoperative dysphagia and dysphonia is relative higher after multilevel anterior operation. Age and operation time carry a greater risk of postoperative dysphagia and dysphonia. Tracheal traction exercise might help patients reduce postoperative dysphagia. Sufficient preoperative preparation and evaluation combining with proficient and precise operation technique are suggested when multilevel anterior fusion is performed.


Sampling of the telescope image plane using single- and few-mode fibre arrays.
The coupling efficiency of starlight into single and few-mode fibres fed with lenslet arrays to provide a continuous field of view is investigated. The single-mode field of view (FOV) and overall transmission is a highly complicated function of wavelength and fibre size leading to a continuous sample only in cases of poor throughput. Significant improvements are found in the few-mode regime with a continuous and efficient sample of the image plane shown to be possible with as few as 4 modes. This work is of direct relevance to the coupling of celestial light into photonic instrumentation and the removal of image scrambling and reduction of focal ratio degradation (FRD) using multi-mode fibre to single-mode fibre array converters.


[The patient exhibited; clinical demonstration and clinical lessons in the Nederlandsch Tijdschrift voor Geneeskunde].
The evolution of clinical demonstrations and of the illustrations is discussed, with reference to the importance of sharpening observation as a medical method. It is especially in the section 'Clinical Lessons' in the Nederlandsch Tijdschrift voor Geneeskunde that the way in which the patient is shown in illustrations is considered in detail, including the question to what extent limits were imposed on what was considered permissible in illustrations.


Blastocystis ST-1 is associated with Irritable Bowel Syndrome-diarrhoea (IBS-D) in Indonesian adolescences.
IBS is a functional gastrointestinal disorder and commonly presents in children and adolescences, presented as diarrhoea, constipation or mixed type. Blastocystis is a common intestinal protozoa found worldwide, which pathogenicity is still controversial. This study aimed to identify the risk factors of IBS, the association between IBS types with Blastocystis subtypes and analyse Blastocystis pathogenicity. A comparative cross-sectional study was conducted among senior high school students. Rome III Criteria for IBS diagnosis, questionnaires on the risk factors of IBS and types of IBS were recorded. Students were further selected and classified into IBS and non-IBS groups to analyse the association between IBS, IBS types with Blastocystis infection and its subtypes. Direct microscopic stool examination to identify single Blastocystis infection was performed, followed by culture in Jones' medium, PCR, sequencing of 18S rRNA and phylogenetic analysis to determine Blastocystis subtype. Data was analysed using SPSS v22.0 and P value <0.05 was considered statistically significant (95% confidence intervals). IBS was found in 30.2% of 454 students, consisted of 33.3% IBS Diarrhoea, 27.7% IBS Mixed, 27.7% IBS Unclassified and 11.1% IBS Constipation. Major risk factors to IBS consisted of family history of recurrent abdominal pain, abuse, bullying and female gender in respective order (OR 3.6-2.1). Blastocystis ST-1 was significantly associated to IBS-D with 2.9 times risk factor. Blastocystis infection is a risk factor to develop IBS-D type in adolescence; Blastocystis ST-1 can be regarded as a pathogenic subtype.


Nurse psychotherapists' experiences in obtaining individual practice privileges.
Nurses who function as primary care providers often want direct access to hospitalized clients. Individual practice privileges provide one means by which such providers can admit and treat their clients in institutional settings. This article describes a study in which nurse psychotherapists report their experiences in obtaining individual staff privileges. Findings of the study have implications for other primary care nurses seeking such privileges. The authors conclude that current conditions within the health care system may be favorable in facilitating individual practice privileges for nurses.


Establishment of reference intervals for immunoassay analytes of adult population in Saudi Arabia.
Background This is a second part of report on the IFCC global multicenter study conducted in Saudi Arabia to derive reference intervals (RIs) for 20 immunoassay analytes including five tumor makers, five reproductive, seven other hormones and three vitamins. Methods A total of 826 apparently healthy individuals aged ≥18 years were recruited in three clinical laboratories located in western, central and eastern Saudi Arabia using the protocol specified for the global study. All serum specimens were measured using Abbott, Architect analyzers. Multiple regression analysis (MRA) was performed to explore sources of variation of each analyte: age, body mass index (BMI), physical exercise and smoking. The magnitude of variation of reference values (RVs) attributable to sex, age and region was calculated by ANOVA as a standard deviation ratio (SDR). RIs were derived by the parametric (P) method. Results MRA revealed that region, smoking and exercise were not relevant sources of variation for any analyte. Based on SDR and actual between-sex differences in upper limits (ULs), we chose to partition RIs by sex for all analytes except for α-fetoprotein and parathyroid hormone (PTH). Age-specific RIs were required in females for ferritin, estradiol, progesterone, testosterone, follitropin, luteotropin and prolactin (PRL). With prominent BMI-related increase, RIs for insulin and C-peptide were derived after excluding individuals with BMI > 32 kg/m2. Individuals taking vitamin D supplements were excluded in deriving RIs for vitamin D and PTH. Conclusions RIs of major immunoassay analytes specific for Saudi Arabians were established in careful consideration of various biological sources of variation.


Ethical and public policy challenges for pharmacogenomics.
It is timely to consider the ethical and social questions raised by progress in pharmacogenomics, based on the current importance of pharmacogenomics for avoidance of predictable side effects of drugs, and for correct choice of medications in certain cancers. It has been proposed that the entire population be genotyped for drug-metabolizing enzyme polymorphisms, as a measure that would prevent many untoward and dangerous drug reactions. Pharmacologic treatment targeting based on genomics of disease can be expected to increase greatly in the coming years. Policy and ethical issues exist on consent for large-scale genomic pharmacogenomic data collection, public vs corporate ownership of genomic research results, testing efficacy and safety of drugs used for rare genomic indications, and accessibility of treatments based on costly research that is applicable to relatively few patients. In major psychiatric disorders and intellectual deficiency, rare and de novo deletion or duplication of chromosomal segments (copy number variation), in the aggregate, are common causes of increased risk. This implies that the policy problems of pharmacogenomics will be particularly important for the psychiatric disorders.


Postsynaptic potentials mediated by excitatory and inhibitory amino acids in interneurons of stratum pyramidale of the CA1 region of rat hippocampal slices in vitro.
1. Because interneurons of stratum pyramidale partly mediate the feed-forward inhibition of pyramidal cells, intracellular postsynaptic potentials (PSPs) evoked by activation of afferent fibers were examined in 32 nonpyramidal cells of stratum pyramidale of the CA1 region of rat hippocampal slices. 2. Electrical stimulation of stratum radiatum at the CA1-CA3 border elicited, in interneurons, PSPs that were composed of four components: a fast excitatory postsynaptic potential (EPSP), an early inhibitory postsynaptic potential (IPSPA), a late IPSPB, and in some cells a delayed, slower EPSP. These synaptic potentials summated and elicited single action potentials in 57% of cells (17/30) and burst of action potentials (2-10) in the remaining 43%. 3. The fast EPSP was observed in all cells, and the mean stimulation intensity at its threshold was 53.4 microA. Its amplitude increased with membrane hyperpolarization, and it was associated with a 45.4% decrease in cellular input resistance. The fast EPSP always elicited an action potential at short latencies (3.6-6.4 ms poststimulation). It was reversibly reduced by 6-cyano-7-nitroquinoxaline-2,3- dione (CNQX), a blocker of non-N-methyl-D-aspartate (non-NMDA) excitatory amino acid receptors. 4. The IPSPA was observed in 28/32 cells, and the mean intensity of stimulation was 57.6 microA at its threshold. The mean latency of its peak amplitude was 17.4 ms. The mean equilibrium potential (Erev) was -72.8 mV, and it was associated with a 38.9% decrease in cellular input resistance. IPSPA was blocked by the GABAA antagonist bicuculline. 5. The IPSPB was seen in 29/32 cells, and the mean intensity of stimulation at its threshold was 80.3 microA. Its latency to peak was 130.6 ms, its Erev was -107.6 mV, and it was associated with a small (7.6%) decrease in cellular input resistance. IPSPB was blocked by the GABAB antagonist phaclofen. 6. In 11/32 cells a slower EPSP was also observed. Its mean latency to peak was 53.3 ms, and the mean intensity of stimulation at its threshold was 89.4 microA. In two cells its amplitude decreased with membrane hyperpolarization, and its was associated with a 6.8% increase in cellular input resistance. In 8 of 13 cells showing burst responses, this slow EPSP was present. 7. Both EPSPs and IPSPs were sensitive to repetitive stimulation. The amplitude of the fast EPSP was potentiated during paired-pulse stimulation at interstimulus intervals between 30 and 200 ms and occasionally depressed at intervals of 10-20 ms.(ABSTRACT TRUNCATED AT 400 WORDS)


Adrenal arteriography and venography.
Although no longer the primary diagnostic examination, angiography of the adrenal gland remains a safe, reliable tool for identifying adrenal disorders. Selective venous sampling for hormone assay is important in localizing functional adrenal lesions.


Distribution of mesopredatory fish determined by habitat variables in a predator-depleted coastal system.
Shallow nearshore habitats are highly valued for supporting marine ecosystems, but are subject to intense human-induced pressures. Mesopredatory fish are key components in coastal food webs, and alterations in their abundance may have evident effects also on other parts of the ecosystem. The aim of this study was to clarify the relationship between the abundance of coastal mesopredatory fish, defined as mid-trophic level demersal and benthic species with a diet consisting predominantly of invertebrates, and ambient environmental variables in a fjord system influenced by both eutrophication and overfishing. A field survey was conducted over a coastal gradient comprising 300 data points sampled consistently for fish community and environmental data. Results from multivariate and univariate analyses supported each other, demonstrating that mesopredatory fish abundance at species and functional group level was positively related to the cover of structurally complex vegetation and negatively related to eutrophication, as measured by water transparency. Contrary to other studies showing an inverse relationship to piscivore abundance over time, the spatial distribution of mesopredatory fish was not locally regulated by the abundance of piscivorous fish, probably attributed to piscivores being at historically low levels due to previous overfishing. Mesopredatory fish abundance was highest in areas with high habitat quality and positively related to the abundance of piscivores, suggesting a predominance of bottom-up processes. We conclude that, in parallel with ongoing regulations of fishing pressure, measures to restore habitat function and food web productivity are important for the recovery of coastal fish communities in the area.