Glycoprotein galactosyltransferase activity in synaptic junctional complexes isolated from rat forebrain.
A synaptosomal plasma membrane fraction and its junctional and nonjunctional subfractions were isolated and analyzed for glycoprotein galactosyltransferase activity. The nonjunctional components fraction had the highest specific activity in the presence of exogenous acceptor, suggesting an enrichment of enzyme in this fraction. The synaptic junctional complex fraction had the highest specific activity in the absence of added acceptor, suggesting that there is a relative enrichment of endogenous acceptors for this galactosyltransferase within the synaptic junctional complex.


Health state preference scores of children with spina bifida and their caregivers.
Cost-effectiveness evaluations of interventions to prevent or treat spina bifida require quality of life information measured as preference scores. Preference scores of caregivers also may be relevant. This study tested whether the preference scores of children with spina bifida and their caregivers would decrease as disability in the child increased. Families of children aged 0-17 with spina bifida (N = 98) were identified using a birth defect surveillance system in the state of Arkansas. Primary caregivers of children with spina bifida identified other families with an unaffected child (N = 49). Preference scores for child health states were determined using the Health Utilities Index--Mark 2 (HUI2). Caregiver preference scores were determined using the Quality of Well-Being (QWB) scale. Children with spina bifida were categorized into three disability levels according to the location of the child's lesion. Mean preference scores declined for both affected children and the primary caregiver as disability in the child increased. In multivariate analysis, the preference score of the child was a significant and positive predictor of the primary caregiver's preference score. A more modest association was found for caregiver health preference scores by lesion location. The findings can inform cost-effectiveness evaluations of interventions to treat or prevent spina bifida.


Emerging infections: mimickers of common patterns seen in dermatopathology.
The following discussion deals with three emerging infection diseases that any dermatopathologist working in the northern hemisphere can come across. The first subject to be dealt with is gnathostomiasis. This parasitic disease is produced by the third larvarial stage of the parasite that in most patients is associated with the ingestion of raw fish. Epidemiologically, it is most commonly seen in South East Asia, Japan, China, and the American continent, mainly in Mexico, Ecuador, and Peru. Nowadays, the disease is also seen in travelers living in the developed countries who recently came back from visiting endemic countries. The disease produces a pattern of migratory panniculitis or dermatitis with infiltration of eosinophils in tissue. The requirements for making the diagnosis are provided, including clinical forms, common histological findings on skin biopsy as well as the use of ancillary testing. Buruli ulcer, a prevalent mycobacterial infection in Africa, is described from the clinical and histopathological point of view. The disease has been described occasionally in Central and South America as well as in developed countries such as Australia and Japan; Buruli ulcer has also been described in travelers returning from endemic areas. Clinically, the disease is characterized by large, painless ulcerations with undermined borders. Systemic symptoms are usually absent. Classical histological findings include a particular type of fat necrosis and the presence of abundant acid fast bacilli in tissue. Such findings should raise the possibility of this disease, with the purpose of early therapeutically intervention. Lastly, the infection by free living ameba Balamuthia mandrillaris, an emerging condition seen in the US and Peru, is extensively discussed. Special attention is given to clinical and histological characteristics, as well as to the clues for early diagnosis and the tools available for confirmation.


Molecular basis of sperm-egg interaction and the prospects for immunocontraception.
As the molecular basis of sperm-egg interaction is resolved, so new opportunities are created for the development of immunological approaches to disrupt the process of conception. Thus, realisation that the zona glycoprotein, ZP3, serves as a specific receptor for spermatozoa, has prompted a detailed examination of its contraceptive potential. In primate models, recombinant ZP3 has been shown to suppress fertility very efficiently, however this efficacy is tempered by the appearance of adverse side-effects involving accelerated primordial follicle depletion and a lymphocytic infiltration of the ovarian stroma. Synthetic peptides encoding B-cell epitopes have been found to circumvent the lymphocyte response although the effectiveness of such reagents in preventing the loss of primordial follicles has not yet been determined. The induction of active immunity against sperm-specific antigens has also been shown to generate long term infertility in both males and females. Molecular and immunological techniques are now being used to produce a rapidly expanding list of unique sperm antigens which are currently being evaluated to determine their potential contribution to the development of safe, effective, contraceptive vaccines.


An empirical model for predicting microhabitat of 0+ juvenile fishes in a lowland river catchment.
Species-habitat relationships are an important aspect of fish life history, particularly in early ontogeny. To address the lack of information on the microhabitat use/requirements of European coarse fishes, particularly 0-group fishes in riverine systems, an empirical model was generated from data collected in the River Great Ouse catchment (UK). During 7 weeks in autumn 1990, data on young-of-the-year (0+) juvenile fishes and 15 environmental variables were collected at 2800 stratified, random point samples within 130 study sites (streams, rivers, side-channels, backwaters). Of 24 species of 0+ fish, only 10 were captured in ≥ 3% of non-null samples. Association analysis and canonical correspondence analysis of the samples-by-species (967×10) and samples-by-variables (967×15) data matrices revealed that the shallow, narrow, lotic, stony-pebbly channel microhabitat of riffles and runs was preferred by the progeny of substrate-spawning, substrate/plant-spawning and nest-guarding fishes. Moderately deeper and wider, sinuous channels, with slowto-moderate water velocities and medium-sized substrata were also favourable to progeny of substrate spawners. Assemblages of 0+ fish in deeper, wider, silted, trapezoidal-shaped channels with slow-to-lentic flowing water, i.e. channelised and regulated, were dominated by ubiquitous (plant/substrate) spawners.


Verapamil attenuates postischemic oxidative injury in the rat liver.
We assessed the effects of the calcium channel blocker verapamil on postischemic oxidative injury in the rat liver. In the untreated rats, the values of tissue lipid peroxidation products (thiobarbituric acid-reactive substances) remained unchanged during 90 min of warm ischemia. However, the values increased significantly after the next 60 min of reperfusion compared with those in the sham-operated rats (P less than 0.01). Intravenous infusion of verapamil (5 micrograms.kg-1.min-1) significantly reduced the extent of lipid peroxidation during reperfusion compared with that in the untreated rats (P less than 0.02). The percentages of tissue water content and the serum lactate dehydrogenase activities after 60 min of reperfusion were significantly lower in the treated rats than in the untreated rats (P less than 0.02 and P less than 0.01, respectively). We also investigated the influence of verapamil on superoxide-generating activity determined by the superoxide-dependent cytochrome c reduction of peritoneal polymorphonuclear leukocytes (PMNs) harvested from normal, non-ischemic, and non-treated rats in vitro. This demonstrated that there was no apparent effect with the highest verapamil concentration level (8 microM) observed in the rat plasma during our experiment. These findings suggest that verapamil might reduce the postischemic oxidative injury in the rat liver by mechanisms perhaps not related to the suppression of rat PMNs superoxide-generating activity.


Visual detection of single-base mismatches in DNA using hairpin oligonucleotide with double-target DNA binding sequences and gold nanoparticles.
We describe a hairpin oligonucleotide (HO) with double-target DNA binding sequences in the loop and 11-base in the stem for visual detection of single-base mismatches (SBM) in DNA with highly specificity. The thiol-modified HO was immobilized on gold nanoparticle (Au-NP) surface through a self-assembling process. The strategy of detecting SBM depends on the unique molecular recognition properties of HO to the perfect-matched DNA and SBM to generate different quantities of duplex DNA on the Au-NP surface, which are captured on the test zone of lateral flow test strip via the DNA hybridization reaction between the duplex DNA and preimmobilized DNA probe. Accumulation of Au-NPs produces the characteristic red bands, enabling visual detection of SBM. It was found that the ability of HO to differentiate perfect-matched DNA and SBM was increased dramatically by incorporating double-target DNA binding sequences in the loop of HO. The signal ratio between perfect-matched DNA and SBM was up to 28, which is much higher than that of conventional HO or molecular beacon. The approach was applied to detect the mutation sites, Arg142Cys and Gly529Ile, of transglutaminase 1 gene in autosomal recessive congenital ichthyosis. The results presented here show that the new HO is a potential molecular recognition probe for the future development of nucleic acid-based biosensors and bioassays. The approach can be used for point-of-care diagnosis of genetic diseases and detecting infectious agents or warning against bio-warfare agents.


A disposable immunosensor for detection of 17beta-estradiol in non-extracted bovine serum.
This paper reports the assembly of a disposable immunosensor based on the direct competitive enzyme-linked immunosorbent assay (ELISA), for simple and fast measurement of 17beta-estradiol (17beta-E2) in bovine serum, using screen-printed electrodes (SPEs) and a Palm-Sens portable electrochemical detector. The immunosensor strip was assembled immobilising, by passive adsorption, anti-rabbit IgG onto the surface of the working SPE electrode. After the interaction between anti-rabbit IgG and rabbit anti-17beta-E2 polyclonal antibodies (PAb), the competition was performed using 17beta-estradiol-alkaline phosphatase conjugate (17beta-E2-AP) synthesised in our laboratory. The enzymatic substrate used for signal generation was 1-naphthylphosphate and its conversion to an electroactive product (1-naphthol) was measured using differential pulse voltammetry (DPV). To develop a prototype for field measurements, the entire competitive protocol has been optimised directly in a blank non-extracted bovine serum. According to the new EU criteria established by the Commission Decision 2002/657/EC for qualitative and quantitative screening methods, the detection capability (CCbeta), was determined. The CCbeta value resulted below the action limit (40 pg mL(-1)) fixed for 17beta-E2) Spiked and real samples were analysed using the electrochemical immunostrips obtaining precision values (relative standard deviation, R.S.D.%) ranging from 8.6 to 17.0% and a recovery (R%) from 88.2 to 120.0%. Results obtained on real samples were confirmed by liquid chromatography coupled on-line with tandem mass spectrometry (LC-MS/MS) using an atmospheric pressure chemical ionisation (APCI) source and a heated nebulizer (HN) interface; this is the method currently used to confirm illegal hormone administration for regulatory purposes. The disposable immunosensor appears suitable as a screening tool for field analysis of bovine serum estradiol.


A 31-year-old female patient with chronic kidney disease presenting with persistent cough.
Can you diagnose this 31-year-old woman with end-stage renal disease and a persistent cough? https://bit.ly/3s7n5VU.


Toll-like receptor 4 initiates an innate immune response to lipopolysaccharide in human conjunctival epithelial cells.
Conjunctival epithelial cells serve as a first line of defense against pathogens presented to the innate immune system. The inflammatory response to Gram-negative bacteria is initiated by toll-like receptor 4 (TLR4). This study investigated whether a TLR4 ligand induces production of inflammatory cytokines in human conjunctival epithelial cells (HCECs) through nuclear factor kappa-B (NF-kappaB). HCECs were evaluated for TLR4 expression by reverse transcriptase-polymerase chain reaction, Western blot analysis, and flow cytometric analysis. HCECs were stimulated with various concentrations of lipopolysaccharide (LPS) and the innate immune response was quantified by measuring expression of the inflammatory cytokines IL-6 and IL-8. Functional NF-kappaB activation was examined using a luciferase reporter assay. Expression of TLR4-specific mRNA as well as its corresponding protein was observed in HCECs. Surface and intracellular expression of TLR4 was observed in flow cytometric analysis. Incubation of HCECs with LPS led to secretion of IL-6 and IL-8. Blockade of TLR4- and TNFR-associated factor (TRAF) 6 activity abolished LPS-induced inflammatory response in HCECs and incubation of HCECs with LPS led to activation of the NF-kappaB transcription factor. LPS did not enhance the TLR4 expression at both mRNA and protein levels in HCECs. Our results demonstrate that surface expression of TLR4 in HCECs can elicit a TLR4-mediated innate immune response through TRAF6-NF-kappaB and contribute to an inflammatory environment on the ocular surface.


Clinical ratings and plasma HVA during cocaine abstinence.
Six patients were evaluated over a 21-day period during inpatient recovery from chronic repeated cocaine use. Serial evaluations of Hamilton depression rating, cocaine craving, plasma homovanillic acid (pHVA), and plasma 3-methoxy-4-hydroxyphenylethyleneglycol (pMHPG) concentrations were determined. There was a distinct increase in cocaine craving between 1 and 2 weeks after the last cocaine use. Levels of pHVA also increased at the time of heightened craving. The data provide preliminary evidence to suggest that changes in cocaine craving during abstinence are positively correlated with changes in dopamine turnover.


Developing environment-specific water quality guidelines for suspended particulate matter.
It is generally well recognised that suspended particulate matter (SPM), from nano-scale particles to sand-sized sediments, can cause serious degradation of aquatic ecosystems. However, at present there is a poor understanding of the SPM conditions that water quality managers should aim to achieve in contrasting environments in order to support good ecological status. In this article, we analyse long-term SPM data collected from a wide range of reference-condition temperate environments in the UK (638 stream/river sites comprising 42 different ecosystem-types). One-way analysis of variance reveals that there is a statistically significant difference (p < 0.001) between the background SPM concentrations observed in contrasting ecosystems that are in reference condition (minimal anthropogenic disturbance). One of the 42 ecosystems studied had mean background concentrations of SPM in excess of the current European Union (EU) water quality guideline, despite being in reference condition. The implications of this finding are that the EU's current blanket water quality guideline (25 mg L(-1) for all environments) is inappropriate for this specific ecosystem-type which will be non-compliant with the guideline regardless of the intensity of land-use. The other 41 ecosystems studied had mean concentrations below the current EU water quality guideline. However, this does not necessarily mean that the guideline is appropriate for these ecosystems, as previous research has demonstrated that detrimental impacts can be experienced by some freshwater organisms, of all trophic levels, when exposed to concentrations below 25 mg L(-1). Therefore, it is suggested here that it is likely that some ecosystems, particularly those with mean concentrations in the 0.00-5.99 mg L(-1) range, require much lower guideline values in order to be effectively protected. We propose a model for predicting environment-specific water quality guidelines for SPM. In order to develop this model, the 638 reference condition sites were first classified into one of five mean background SPM ranges (0.00-5.99, 6.00-11.99, 12.00-17.99, 18.00-23.99 and >24.00 mg L(-1)). Stepwise Multiple Discriminant Analysis (MDA) of these ranges showed that a site's SPM range can be predicted as a function of: mean annual air temperature, mean annual precipitation, mean altitude of upstream catchment, distance from source, slope to source, channel width and depth, the percentage of catchment area comprised of clay, chalk, and hard rock solid geology, and the percentage of the catchment area comprised of blown sand as the surface (drift) material. The MDA technique, with cross-validation (Wilks-Lambda 0.358, p 0.000), can predict the correct or the next closest SPM range of a site in 90% of cases. This technique can also predict SPM range membership in a probabilistic manner, allowing for an estimate of uncertainty to be made in the allocation of a site to an environment-specific SPM range.


Patient evaluation of the use of follitropin alfa in a prefilled ready-to-use injection pen in assisted reproductive technology: an observational study.
Self-administration of recombinant human follicle-stimulating hormone (r-hFSH) can be performed using injection pen devices by women undergoing assisted reproductive technology procedures. The objective of this study was to explore the use of the prefilled follitropin alfa pen in routine assisted reproductive technology procedures in Germany. This prospective, observational study was conducted across 43 German IVF centres over a period of 1.75 years. Patients who had used the prefilled follitropin alfa pen in the current or a previous cycle of controlled ovarian stimulation completed a questionnaire to assess their opinions of the device. A total of 5328 patients were included in the study. Of these, 2888 reported that they had previous experience of daily FSH injections. Significantly more patients reported that less training was required to use the prefilled follitropin alfa pen than a syringe and lyophilized powder (1997/3081 [64.8%]; p < 0.001 'less' versus 'more' training). Significantly more patients rated the prefilled follitropin alfa pen as easier in terms of use (2321/3206, 72.4%; p < 0.001 'much more easy' versus 'less easy') and daily injection (2384/3262, 73.1%; p < 0.001 'much more easy' versus 'less easy') than existing injection methods. Approximately one third of respondents rated the prefilled follitropin alfa pen as easier to use than the follitropin beta pen with reloadable cartridges. The majority (3378/4024, 83.9%) of patients had a general preference for the prefilled follitropin alfa pen over other injection methods. In this questionnaire-based survey, routine use of the prefilled follitropin alfa pen was well accepted and associated with favourable patient perceptions. Users of the pen found it easier to initially learn how to use, and subsequently use, than other injection methods. In general, the prefilled follitropin alfa pen was the preferred method for self-administration of gonadotrophins. Together with previous findings, the results here indicate a high level of patient satisfaction among users of the prefilled follitropin alfa pen for daily self-administration of r-hFSH.


A comparative investigation of the restorative effects of roxithromycin on neutrophil activities.
The effects of roxithromycin, a macrolide antibiotic, on neutrophil activities were investigated in six seriously handicapped patients with severe mental retardation. Neutrophil activities were evaluated by flow cytometry using a heparinized blood analysis method. All six patients showed decreased levels of neutrophil phagocytosis, intracellular killing, and CD11b expression. Treatment with roxithromycin in vitro selectively restored the decreased phagocytic and bactericidal activities of neutrophils in these patients. There was no significant restorative effect with cefaclor, ofloxacin, or aztreonam. These results suggest the need to consider therapeutic effects of antibiotics on neutrophil functions in patients at increased risk for bacterial infections due to decreased neutrophil activities.


Deconstructing Community for Conservation: Why Simple Assumptions are Not Sufficient.
Many conservation policies advocate engagement with local people, but conservation practice has sometimes been criticised for a simplistic understanding of communities and social context. To counter this, this paper explores social structuring and its influences on conservation-related behaviours at the site of a conservation intervention near Pipar forest, within the Seti Khola valley, Nepal. Qualitative and quantitative data from questionnaires and Rapid Rural Appraisal demonstrate how links between groups directly and indirectly influence behaviours of conservation relevance (including existing and potential resource-use and proconservation activities). For low-status groups the harvesting of resources can be driven by others' preference for wild foods, whilst perceptions of elite benefit-capture may cause reluctance to engage with future conservation interventions. The findings reiterate the need to avoid relying on simple assumptions about 'community' in conservation, and particularly the relevance of understanding relationships between groups, in order to understand natural resource use and implications for conservation.


Cerebral function of bone marrow multipotent adult progenitor cells after transplantation in Parkinson's disease rat models.
This study sought to explore the mechanism of bone marrow-derived multipotent adult progenitor cell (MAPC) differentiation into neurons to restore functional deficits. We were successfully established a rat model of Parkinson's disease (PD). MAPC were injected into the left striatum for cellular identification. At 3 months after the injection, behavioral tests, immunofluorescence reverse-transcriptase polymerase chain reaction (PCR) and electron microscopy were used to evaluate the rats. Compared with control animals, MAPC-derived dopaminergic neurons caused gradual, sustained behavioral restoration of dopamine-mediated motor asymmetry. Within 1 hour, the impaired gait of the rats in the MAPC group was improved compared with the control group (P < .05). After implantation, the MAPCs survived and differentiated into neuronlike cells in the substantia nigra and striatum including dopaminergic neurons. Real-time PCR revealed significantly higher dopamine-β-hydroxylase (1.64-fold increase), dopamine transporter (1.55-fold increase), and nerve growth factor (1.77-fold increase) mRNA levels in the MAPC group, suggesting that MAPC-derived neurons perform the function of dopaminergic neurons. The immature synapses under electron microscopy show that MAPC-derived neurons have great potential in the reconstruction of the neural circuitry. Transplanted MAPCs develop spontaneously into dopaminergic neurons, which restore cerebral function and behavior in PD rat models.


In vitro evaluation of antioxidant, cytotoxic, trypanocidal and antimicrobial activities of lignin obtained from Caesalpinia ferrea leaves and its use as an excipient in the release of oxacillin and fluconazole.
In this context, the objective of this work was to isolate an alkaline lignin from the leaves of C. ferrea, in addition to investigating different biological activities and its use in the production of releasing tablets in vitro. Initially, the analysis of the composition of the leaves was performed, the contents were: cellulose (33.09 ± 0.3 %), hemicellulose (25.13 ± 0.1 %), lignin (18.29 ± 0.1 %), extractives (17.28 ± 1.0 %) and ash (6.20 ± 0.1 %). The leaves were fractionated to obtain alkaline lignin. The yield of obtaining lignin was 80.12 ± 0.1 %. The obtained lignin was characterized by the techniques: elemental analysis, FTIR, UV/Vis, 2D-NMR, GPC, TGA/DTG, DSC and PY-GC/MS. The results showed that the lignin obtained is of the GSH type, of low molecular weight and thermally stable. The in vitro antioxidant activity was evaluated by different assays promoting results only for DPPH (559.9 ± 0.8 μg/mL) and ABTS (484.1 ± 0.1 μg/mL) being able to promote low antioxidant activity. In addition, it showed low cytotoxicity in normal mammalian cells and promising antitumor and trypanocidal activity. Regarding antimicrobial activity, it was able to inhibit the growth of a strain of Staphylococcus aureus resistant to methicillin, presenting MIC values equal to the standard antibiotic oxacillin. It was also able to inhibit a strain of Candida albicans HAM13 sensitive to fluconazole. In addition, lignin promoted a synergistic effect by promoting a decrease in MIC against these two strains evaluated. Finally, lignin proved to be an excipient with potential for controlled release of antimicrobials.


Persisting eustachian valve in adults: relation to patent foramen ovale and cerebrovascular events.
The eustachian valve (EV) (valvula venae cavae inferioris) is a remnant of the embryonic right valve of the sinus venosus. Embryologically, the EV directs oxygenated blood from the inferior vena cava across the patent foramen ovale (PFO) into the systemic circulation. Transthoracic echocardiography shows the EV in the majority of newborns, but the prevalence of EV in adults studied with transesophageal echocardiography is unknown. We studied whether the presence of an EV is associated with PFO or with cryptogenic stroke. The frequency and size of the EV was studied in 211 consecutive patients undergoing transesophageal echocardiography after a cryptogenic stroke and in 95 consecutive patients without cerebrovascular events. In all 306 patients, the presence of a PFO was studied with 2-dimensional transesophageal echocardiographic, color Doppler, and contrast echocardiographic studies. An EV was seen in 174 of 306 patients overall (57%). The mean size was 1.0 +/- 0.4 cm (range: 0.5-2.0); 70% of patients with an EV had a PFO (Cohen's kappa = 0.75; P <.001). This relationship was not significantly influenced by a cryptogenic stroke. The prevalence of PFO was 30% in the control group and 61% for those with presumed paradoxical embolism (P <.001). Thus, an EV was more common for patients with presumed paradoxical embolism than in control patients (143 of 211 68% vs 31 of 95 33%, respectively, P <.001). There was no significant difference in the size of the EV between the 2 groups (1.1 vs 1.0 cm; P =.24). A persisting EV is a frequent finding in patients with a PFO. By directing the blood from the inferior cava to the interatrial septum, a persisting EV may prevent spontaneous closure of PFO after birth and may, therefore, indirectly predispose to paradoxical embolism.


Human p53 tumor suppressor gene (TP53) and schizophrenia: case-control and family studies.
The human p53 tumor suppressor gene (TP53) is considered as a candidate susceptibility gene for schizophrenia because of its functions in neurodevelopment. To test for an association between TP53 and schizophrenia, both the case-control study and the transmission disequilibrium test (TDT) were performed on genotype data from eight polymorphisms in TP53. Our samples included 286 Toronto schizophrenia cases and 264 controls, and 163 Portuguese nuclear families. In the Toronto case-control study significant differences of allele frequencies of the CAA Ins/Del (p=0.027) and the 16bp Ins/Del (p=0.022) were detected. In TDT analysis we found significant differences for transmission of the CAA Ins/Del (p=0.017) in Portuguese schizophrenia families. Haplotype analysis also showed a significant association between TP53 and schizophrenia. These results provide further evidence that TP53 may play a role in the pathogenesis of schizophrenia.


Bovine torovirus: sequencing of the structural genes and expression of the nucleocapsid protein of Breda virus.
Breda virus (BRV), a member of the genus torovirus, is an established etiological agent of diarrhea of cattle, which is found as two separate serotypes, BRV-1 and BRV-2. In this study, a 7.5 kb fragment of the BRV-1 genome that bracketed the genes for the structural proteins of BRV was amplified by long RT-PCR and the amplicon purified and sequenced directly. Sequence analysis revealed the presence of four open reading frames (ORF) corresponding to the peplomer (S), envelope (M), and nucleocapsid (N) genes, and an ORF for a novel 1.2 kb gene located between the M and N genes. This new gene was identical in nucleotide sequence to the hemagglutinin-esterase (HE) gene of BRV-2. With the exception of this new ORF, BRV-1 manifests 80% nucleotide sequence identity with the torovirus prototype, Berne virus (BEV) in the 7.5 kb region from the 3' end of the genome that contains the genes for the structural proteins. A 504 base segment containing the ORF for the BRV-1 N gene was amplified by RT-PCR, and cloned into an Escherichia coli expression system. The resulting protein was purified by SDS-PAGE and used to immunize guinea pigs. Hyperimmune serum was reactive with bovine torovirus (BTV) and human torovirus (HTV) antigens. By immunoelectron microscopy, it was shown to aggregate broken but not intact torovirus particles from BTV-positive fecal specimens. By immunoblot, the hyperimmune serum reacted specifically with the 20 kD N proteins of both BTV and HTV, as well as with the expressed N protein. BRV-1 and BRV-2 immune sera from gnotobiotic calves, but not human convalescent sera from HTV-infected patients, reacted with the expressed N protein by immunoblot. These findings were applied to the design of a dot blot assay that could specifically detect BTV and HTV from fecal specimens.


Obesity is not associated with increased knee joint torque and power during level walking.
While it is widely speculated that obesity causes increased loads on the knee leading to joint degeneration, this concept is untested. The purpose of the study was to identify the effects of obesity on lower extremity joint kinetics and energetics during walking. Twenty-one obese adults were tested at self-selected (1.29m/s) and standard speeds (1.50m/s) and 18 lean adults were tested at the standard speed. Motion analysis and force platform data were combined to calculate joint torques and powers during the stance phase of walking. Obese participants were more erect with 12% less knee flexion and 11% more ankle plantarflexion in self-selected compared to standard speeds (both p<0.02). Obese participants were still more erect than lean adults with approximately 6 degrees more extension at all joints (p<0.05, for each joint) at the standard speed. Knee and ankle torques were 17% and 11% higher (p<0.034 and p<0.041) and negative knee work and positive ankle work were 68% and 11% higher (p<0.000 and p<0.048) in obese participants at the standard speed compared to the slower speed. Joint torques and powers were statistically identical at the hip and knee but were 88% and 61% higher (both p<0.000) at the ankle in obese compared to lean participants at the standard speed. Obese participants used altered gait biomechanics and despite their greater weight, they had less knee torque and power at their self-selected walking speed and equal knee torque and power while walking at the same speed as lean individuals. We propose that the ability to reorganize neuromuscular function during gait may enable some obese individuals to maintain skeletal health of the knee joint and this ability may also be a more accurate risk indicator for knee osteoarthritis than body weight.


Comparative potencies of substance P, substance K and neuromedin K on brain substance P receptors.
The relative potency of substance P, substance K and neuromedin K on [3H]substance P binding has been compared in rat brain membrane preparations. Substance K and neuromedin K, two newly isolated substance P-related mammalian peptides, are very weak competitors for [3H]substance P binding sites. It suggests that these two neuropeptides are not acting on the same receptor type as substance P. Moreover, previous substance P receptor classifications are unlikely to be applicable to brain tachykinin receptor sub-types.


Oviposition preference and offspring performance in container breeding mosquitoes: evaluating the effects of organic compounds and laboratory colonisation.
The preference-performance hypothesis predicts that organisms lacking parental care should oviposit in habitats that optimize offspring performance. We investigated preference-performance relationships for the Asian tiger mosquito (Aedes albopictus Skuse) and the southern house mosquito (Culex quinquefasciatus Say) (Diptera:Culicidae), two medically important container-breeding species, in response to an organic chemical blend mimicking decaying plant matter. Additionally, we evaluated the effects of long-term laboratory colonization of Cx. quinquefasciatus by using wild and laboratory strains.Oviposition bioassays were conducted by releasing gravid mosquitoes into field enclosures with automobile tires containing low and high concentrations of the chemical blend, and water controls. The offspring were then reared in water collected from the tires in which they were deposited.Aedes albopictus and wild Cx. quinquefasciatus laid more eggs in the chemical blend than water controls but did not differentiate between the low and high concentrations. Conversely, laboratory Cx. quinquefasciatus only preferred the high concentration to the low concentration. No statistical associations between oviposition preference and larval survival were found, as the chemical blend did not affect survivorship of either species.The oviposition preference for the chemical blend over water controls suggests that both species oviposit in the best available resource environment, but further studies are needed before conclusions regarding preference-performance relationships can be drawn.We found that long-term laboratory colonization affects oviposition behavior in Cx. quinquefasciatus, suggesting that behavioral studies on laboratory strains are not always applicable to wild populations.


Syntheses of D-myo-inositol 1,4,5-trisphosphate affinity ligands.
A mixture of 2,3,6-tri-O-benzoyl-4,5-di-O-benzyl-D-myo-inositol and 1,3,6-tri-O-benzoyl-4,5-di-O-benzyl-D-myo-inositol, obtained during our synthesis of D-myo-inositol 1,4,5-trisphosphate [C.E. Ballou and W. Tegge, Proc. Natl. Acad. Sci. U.S.A., 86 (1989) 94-98], was separated after tetrahydropyranylation of the free hydroxyl group in each. 2,3,6-Tri-O-benzoyl-4,5-di-O-benzyl-1-O- (tetrahydro-2-pyranyl)-D-myo-inositol was debenzylated and the two free hydroxyl groups were phosphorylated by a dibenzyl phosphoramidite procedure. The tetrahydropyranyl group was then removed, and phosphorylation at position 1 with benzyl 3-(benzyloxycarbonylamino)propyl di-N-isopropylphosphoramidite, followed by oxidation and deprotection, provided 1-[3-aminopropoxy(hydroxy)phosphinyl]-D-myo-inositol 4,5-bisphosphate. This compound was coupled to activated agarose to prepare an affinity matrix for the isolation of D-myo-inositol 1,4,5-trisphosphate-binding proteins, and it was coupled to 4-azido-2-hydroxybenzoic acid to give a product that was labeled with 125I to prepare a photoactivable derivatizing reagent. The new derivatives retain significant biological activity as assessed by their ability to stimulate the release of stored Ca2+ from the endoplasmic reticulum of permeabilized rat basophilic leukemia cells.


Giant, mushroom-shaped osteoma of the orbit originating from the maxillary sinus.
A 53-year-old woman had a six-month history of proptosis, pain, and decreased vision in the right eye. Skull X-ray films and polytomography demonstrated a giant, mushroom-shaped osteoma originating from the roof of the maxillary sinus and invading the orbit. The tumor was removed by a lateral orbital approach with prompt resolution of proptosis and pain, and recovery of normal vision and ocular motility. This patient is one of 34 patients with 38 paranasal sinus osteomas examined here in the last 25 years. Only six patients have had orbital symptoms or signs.


Current status and future perspective of external herbal dispensaries preparing traditional herbal medicine in South Korea: the first National-Wide Survey results.
An external herbal dispensary (EHD) is a type of pharmacy that provides various types of personalized herbal medicines (PHMs) to other traditional Korean medicine (TKM) institutions. Such dispensaries were legalized by the Ministry of Health and Welfare (MoHW) in 2008 in South Korea. The purpose of this study is to understand the current status of the EHD facilities and their quality controls and compare them with the good manufacture practice (GMP) guidelines to contribute to the establishment of the safety and quality control criteria for PHMs. We contacted 107 EHD representatives or people in charge of the preparation of PHMs (TKM pharmacists) and invited them to complete a survey questionnaire; of the total, 81 responded. The survey questionnaire was developed in 3 stages: drafting, revision by external experts, and final editing. It consisted of 20 questions covering 3 sections: basic characteristics of EHDs, facility, and quality control. The survey was hosted online from December 2017 to January 2018 as guided by the MoHW. The completion rate was 75.7% (n = 81). In terms of facilities, the five facilities (water supply, manufacture, pest control, hygiene management and warehousing) that corresponded to the legal requirements of EHD were mostly equipped, but the types of facilities and equipment differed. Two facilities (sterilization and cross-contamination that were not legally required for EHD were found to have mostly pharmacopuncture-EHD (P-EHD), but hardly any herbal medicine-EHD (H-EHD). In our findings regarding quality control of non-medicinal herbs, sensory evaluation that included checks for foreign bodies and deterioration were conducted. In terms of the quality control of herbal medicines, residual pesticides and heavy metals tests were performed and for pharmacopuncture, pH, salinity, sterility, and endotoxin tests along with gross examination were performed. In the end, we found that 6 of the 38 standard items as required by the Korea GMP were suitable. In this study, detailed information for each existing EHD law was determined through a nationwide questionnaire. Moreover, the basis for its reflection in additional legal standards should be introduced so that safe herbal medicine can be prepared in EHDs.


Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents.
Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.


Pharmacokinetics of lignocaine and bupivacaine in surgical patients following epidural administration. Simultaneous investigation of absorption and disposition kinetics using stable isotopes.
The pharmacokinetics of lignocaine (lidocaine) and bupivacaine following epidural administration were studied in 12 surgical patients using a stable isotope method. Shortly after epidural administration of the agent to be evaluated, a deuterium-labelled analogue was administered intravenously. Plasma concentrations of the unlabelled and the deuterium-labelled local anaesthetics were determined using gas chromatography and mass fragmentography. The pharmacokinetic behaviour of both agents was consistent with a 2-compartment open model and two parallel first-order absorption processes. The mean distribution and elimination half-lives were 12 minutes and 100 minutes for lignocaine, and 22 minutes and 143 minutes for bupivacaine. The mean volumes of the central compartment and the mean steady-state volumes of distribution were: lignocaine, 43L and 99L; bupivacaine, 33L and 68L. Total plasma clearances averaged 0.95 L/min (57 L/h) for lignocaine and 0.52 L/min (31.2 L/h) for bupivacaine. The half-lives, characterising the fast and slow absorption processes, were 9.3 and 82 minutes for lignocaine, and 7.0 minutes and 362 minutes for bupivacaine; the fractions of the doses absorbed in the fast and slow processes were lignocaine 0.38 and 0.58, bupivacaine 0.28 and 0.66, respectively. The results indicate that the local anaesthetics are completely absorbed from the epidural space into the general circulation. The initial absorption rates of both local anaesthetics appear to be similar, but, later, the absorption of bupivacaine proceeds much more slowly than the absorption of lignocaine.


Amorphization-Modulated Metal Sulfides with Boosted Active Sites and Kinetics for Efficient Enzymatic Colorimetric Biodetection.
Colorimetric biosensing has become a popular sensing method for the portable detection of a variety of biomarkers. Artificial biocatalysts can replace traditional natural enzymes in the fields of enzymatic colorimetric biodetection; however, the exploration of new biocatalysts with efficient, stable, and specific biosensing reactions has remained challenging so far. Here, to enhance the active sites and overcome the sluggish kinetics of metal sulfides, the creation of an amorphous RuS2 (a-RuS2 ) biocatalytic system is reported, which can dramatically boost the peroxidase-mimetic activity of RuS2 for the enzymatic detection of diverse biomolecules. Due to the existence of abundant accessible active sites and mildly surface oxidation, the a-RuS2 biocatalyst displays a twofold Vmax value and much higher reaction kinetics/turnover number (1.63 × 10-2 s-1 ) compared to that of the crystallized RuS2 . Noticeably, the a-RuS2 -based biosensor shows an extremely low detection limit of H2 O2 (3.25 × 10-6 m), l-cysteine (3.39 × 10-6 m), and glucose (9.84 × 10-6 m), respectively, thus showing superior detection sensitivity to many currently reported peroxidase-mimetic nanomaterials. This work offers a new path to create highly sensitive and specific colorimetric biosensors in detecting biomolecules and also provides valuable insights for engineering robust enzyme-like biocatalysts via amorphization-modulated design.


The dark choroid in posterior retinal dystrophies.
Fourteen families with genetically determined posterior retinal dystrophies were studied by fluorescein angiography. With one exception, the families could be segregated into two clearly defined categories, one in which every member had a dark choroid, and one where each had a light choroid. This implies that the fluorescein angiography provides a means of subdividing certain of these disorders into more specific disease groups.


The assessment of depression in aphasic stroke patients: the development of the Stroke Aphasic Depression Questionnaire.
The Stroke Aphasic Depression Questionnaire (SADQ) was developed to detect depressed mood in aphasic patients in the community. Correlation analysis between new questionnaire and established measures. Patients at home. Seventy stroke patients who had been discharged from hospital were assessed on the SADQ, the Hospital Anxiety and Depression Scale and the Wakefield Depression Inventory. The SADQ was also administered to 17 aphasic patients on two occasions at a four-week interval. Results indicated that scores on the SADQ were significantly related to other measures of depression (r(s) = 0.22-0.52, p <0.05). A shortened 10-item version showed higher validity (r(s) = 0.32-0.67, p <0.01). Test-retest analysis indicated the SADQ is reliable over a four-week interval (r(s) = 0.72, p <0.001). The SADQ may be used for assessing depressed mood in aphasic patients in the community though further validation is required.


Post-transplant cyclophosphamide as sole GHVD prophylaxis after matched reduced-intensity conditioning allotransplant.
Post-transplant cyclophosphamide (PTCY) alone as graft-versus-host disease (GVHD) prophylaxis may avoid/reduce short- and mid-term toxicities of drugs commonly used for GVHD prophylaxis, accelerate immune reconstitution after the graft to decrease infections and facilitate the early integration of adjunct maintenance therapies to prevent relapse. A prospective phase 2 study was designed in order to assess the feasibility and safety of PTCY as a sole GVHD prophylaxis in adult patients receiving a Baltimore-based reduced-intensity conditioning (RIC) peripheral blood (PB) allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with a matched donor. Patients were planned to be included stepwise up to 59 evaluable PTCY recipients, in order to be able to stop the protocol in case of excessive corticosteroid resistant grade 3-4 severe acute GVHD (aGVHD). Because a high incidence of grade 2-4 aGVHD was observed after analysis of the first 27 patients, the protocol was amended to test the addition of 1 day of anti-thymoglobulin to PTCY. In spite of this, the trial had to be stopped after 38 treated patients, because of an unacceptable rate of grade 3-4 aGVHD. Donors were matched related to 12 patients and unrelated to 26. With a median follow-up of 29.6 months, 2-year overall, disease-free and GVHD-free relapse-free (GRFS) survivals were respectively 65.4%, 62.1% and 46.9%. Cumulative incidences of grade 2-4 and 3-4 aGVHD at day 100 were 52.6% and 21.1%, respectively, while that of moderate/severe chronic(c) GVHD was 15.7% at 2 years. Addition of ATG to PTCY did influence neither aGVHD, cGVHD nor GRFS. Despite paradoxically good survivals, especially GRFS, this study failed to demonstrate that PTCY (± ATG) alone can be used for Baltimore-based RIC PB Allo-HSCT with matched donors. Other combinations should be tested to try and avoid long-term use of immunosuppressive drugs following Allo-HSCT in this setting.


The relation of EGFR expression by immunohistochemical staining and clinical response of combination treatment of nimotuzumab and chemotherapy in esophageal squamous cell carcinoma.
The esophageal squamous cell carcinoma (ESCC) is the predominant pathological type and accounts for more than 80 % of esophageal cancer in China. The successful use of anti-epidermal growth factor receptor (EGFR) treatment in head and neck squamous cell carcinoma provides the rationale for introducing anti-EGFR targeting treatment in ESCC. One of our prospective phase II clinical trials analyzed the efficacy of nimotuzumab, an anti-EGFR agent, combined with chemotherapy (paclitaxel and cisplatin) to treat unresectable ESCC. We analyzed the correlation of the clinical response with EGFR expression by immunohistochemical staining (IHC). Totally 55 tumor samples were analyzed. 18/55 (32.7 %) cases were with high EGFR expression while the other 37/55 (67.3 %) cases were with low to moderate EGFR expression. The expression of EGFR was not related to gender, age, tumor location, tumor differentiation and clinical stage of disease. The objective response rate (ORR) in high EGFR expression group was 55.6 % (10/18) while that in low to moderate EGFR expression group was 54.1 % (20/37) (P = 0.57). Both the progression-free survival (PFS) and overall survival (OS) in high EGFR expression group were much shorter than those in low to moderate EGFR expression group (PFS: 5.8 ± 0.5 vs. 11.0 ± 2.8 months, P = 0.007; OS: 9.7 ± 0.5 vs. 21.5 ± 1.5 months, P = 0.03). The results showed that over-expression of EGFR was related to poor survival of ESCC. The over-expression of EGFR by IHC might not be an ideal predictive biomarker of nimotuzumab treatment. Other EGFR pathway-associated molecules should be analyzed in further studies.


SMYD3 induces sorafenib resistance by activating SMAD2/3-mediated epithelial-mesenchymal transition in hepatocellular carcinoma.
Drug resistance prominently hampers the effects of systemic therapy of sorafenib to hepatocellular carcinoma (HCC). Epigenetics have critical regulatory roles in drug resistance. However, the contributions of histone methylatransferase SET and MYND domain containing 3 (SMYD3) to sorafenib resistance in HCC remain largely unknown. Here, using our established sorafenib-resistant HCC cell and xenograft models, we found SMYD3 was markedly elevated in sorafenib-resistant tumors and cells. Functionally, loss- and gain-of-function studies showed that SMYD3 promoted the migration, invasion, metastasis and stemness of sorafenib-resistant HCC cells. Mechanistically, SMYD3 is required for SMAD2/3-mediated epithelial-mesenchymal transition (EMT) in sorafenib-resistant HCC cells by interacting with SMAD2/3 and epigenetically promoting the expression of SOX4, ZEB1, SNAIL1 and MMP9 genes. In summary, our data demonstrate that targeting SMYD3 is an effective approach to overcome sorafenib resistance in HCC.


The liver X receptors.
The liver X receptors (LXRs), members of the nuclear receptor superfamily, are potential targets for a variety of diseases. While there are many opportunities for the development of LXR-based therapeutics, there are some major hurdles, such as the ability of LXRs to cause hypertriglyceridemia, as well as some species-dependent aspects of LXR-mediated gene regulation. In addition to classical pharmacological approaches using relevant cellular and animal models, systematic molecular-based strategies will be important in overcoming these obstacles.


Copper-containing IUDs are not associated with an increase of malondialdehyde levels in cervical mucus.
The malondialdehyde (MDA) content of cervical mucus from 23 healthy adult females was measured using an ion-pairing HPLC method capable of detecting 10 pmol MDA. Ten of the women were wearing copper IUDs, four were wearing plastic IUDs, and nine controls were not wearing an IUD. Cervical mucus was sampled during the follicular, periovulatory, luteal, and menstrual phases. The study was designed to determine if there is a relationship between MDA formation and the use of a copper IUD. A total of 79 samples were analyzed. Only 16 of the samples had sufficient MDA for reliable quantitation with the level ranging from 0.1 nmol/g to 2.32 nmol/g. In 19 of the samples, trace levels (less than 0.06 nmol/g) were detected but could not be reliably quantitated. In the remaining 44 samples, no MDA was detectable. There was no correlation between the presence of copper- or non-copper-containing IUDs and the level of MDA. These results are contrary to a previously published report that used a less specific method for MDA analysis.


Analytical Considerations of Large-Scale Aptamer-Based Datasets for Translational Applications.
The development and advancement of aptamer technology has opened a new realm of possibilities for unlocking the biocomplexity available within proteomics. With ultra-high-throughput and multiplexing, alongside remarkable specificity and sensitivity, aptamers could represent a powerful tool in disease-specific research, such as supporting the discovery and validation of clinically relevant biomarkers. One of the fundamental challenges underlying past and current proteomic technology has been the difficulty of translating proteomic datasets into standards of practice. Aptamers provide the capacity to generate single panels that span over 7000 different proteins from a singular sample. However, as a recent technology, they also present unique challenges, as the field of translational aptamer-based proteomics still lacks a standardizing methodology for analyzing these large datasets and the novel considerations that must be made in response to the differentiation amongst current proteomic platforms and aptamers. We address these analytical considerations with respect to surveying initial data, deploying proper statistical methodologies to identify differential protein expressions, and applying datasets to discover multimarker and pathway-level findings. Additionally, we present aptamer datasets within the multi-omics landscape by exploring the intersectionality of aptamer-based proteomics amongst genomics, transcriptomics, and metabolomics, alongside pre-existing proteomic platforms. Understanding the broader applications of aptamer datasets will substantially enhance current efforts to generate translatable findings for the clinic.


Methimazole-induced agranulocytosis: growth inhibition of myeloid progenitor cells by the patient's serum.
The mechanism for agranulocytosis induced by antithyroid drugs is not established. The few available studies have proposed an immune-mediated process against mature granulocytes. We investigated the effect of methimazole and propylthiouracil and serum from a patient with methimazole-induced agranulocytosis on marrow myeloid colony growth. In the presence of normal serum or patient's recovery serum, antithyroid drugs had no effect on the growth of CFU-GM colonies from normal or patient's marrow. However, the patient's serum obtained during agranulocytosis inhibited the in vitro myeloid colony growth from both autologous and allogeneic bone marrow. These results are compatible with an immune-mediated mechanism for methimazole-induced agranulocytosis rather than a direct toxic effect of the drug on abnormally sensitive cells.


Inhibition of neointimal proliferation after bare metal stent implantation with low-pressure drug delivery using a paclitaxel-coated balloon in porcine coronary arteries.
A variety of mechanical and laser-based methods remove or shift atherosclerotic plaques and reopen the artery to its original lumen. Subsequent treatment with drug-coated balloons (DCB) may smooth the vessel wall but does not require high-pressure inflation. We investigated the efficacy of paclitaxel-coated balloons inflated with only 2 atm after bare metal stent implantation in coronary arteries of 24 pigs. Angiography and histomorphometry was performed on day 28. DCB inflated with 2 atm caused similar reduction of late lumen loss (LLL) as high-pressure inflation with 12 atm (0.89 ± 0.58 vs. 0.72 ± 0.39 mm, p = 0.34). Both DCB treatments significantly (p < 0.01) reduced LLL versus uncoated balloons (1.50 ± 0.51 mm). Treatment with low-pressure DCB resulted in less maximal intimal thickness (0.45 ± 0.15 vs. 0.67 ± 0.25 mm) and neointimal area (2.93 ± 0.73 vs. 3.82 ± 1.27 mm(2)) than treatment with uncoated balloons (p < 0.05). In conclusion, low-pressure treatment with DCB was similarly effective as high-pressure treatment justifying clinical trials in vessels which will benefit from inhibition of neointimal proliferation but may not tolerate high inflation pressure.


Attachment and trauma-informed programme to support forcibly displaced parents of youth in Sweden: feasibility and preliminary outcomes of the eConnect Online programme.
To assess the feasibility, acceptability and the impact of an online parenting programme for forcibly displaced parents of adolescents. The study was a single-arm feasibility study using pre-intervention post-intervention and follow-up assessments. Participants were recruited from municipality-based activities for refugee parents in a small city in the south of Sweden. Participants were forcibly displaced parents (n=23; 47.8% maternal figures) of youth (n=23; 8-17 years old; 26.1% female) from Syria, Afghanistan and Somalia participating in an online parenting programme (eConnect). eConnect is an attachment-based and trauma-informed parenting intervention and was delivered over the course of 10 weekly sessions. Feasibility was assessed by programme enrolment, attendance, completion and acceptability of the online platform and cultural fit of the programme. Primary outcome measures were programme impact on youth mental health problems. Secondary outcome measures were programme impact on family functioning and parent-child attachment insecurity. The eConnect programme was highly feasible in terms of overall enrolment (100%), attendance (89.6%) and retention rates (100%). The online platform was acceptable, with mixed feedback primarily related to the access and usage of technology. Cultural fit of the programme was acceptable. Youth mental health problems (η 2=0.29) and family functioning significantly improved (η 2=0.18) over the course of the programme. Unexpectedly, parent reports of youth attachment insecurity significantly worsened (η 2=0.16). The findings suggest that the online delivery of Connect was a promising way to reduce barriers to service access and improve mental health problems and family functioning among forcibly displaced parents and their children during COVID-19. Future research is needed to explore the acceptability and impact of this programme post-COVID-19, and to develop culturally tailored and psychometrically sound measures for parent and youth reports of attachment.


Phase II study of everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer.
Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Preliminary results from a phase I study of everolimus and bevacizumab in advanced solid tumors showed it to be a promising combination. The primary objective of this study was to evaluate the 6-month progression-free survival for everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer. Secondary objectives included evaluation of efficacy and safety. In this open-label, single-institution, phase II trial, patients received everolimus 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days on a 28-day cycle. Treatment continued until disease progression or adverse event. Fifty patients were enrolled. Median age was 60.5 years (range 28-82). Forty-six (92%) subjects had measurable disease. Thirteen (26%) (24% adjusted) were progression-free at 6 months (95% CI 16.67-42.71%). One patient had a complete response, while six had a partial response and 35 had stable disease as their best response. Patients with both platinum-sensitive and -resistant disease demonstrated responses, as did some prior bevacizumab exposure. There were two grade 4 and 31 grade 3 toxicities noted in 25 distinct patients. The most common reported toxicities included oral mucositis, fatigue, diarrhea, hypertension, pain, nausea and anorexia. Thirty-eight (76%) patients came off study because of disease progression. Unique molecular profiles were identified in long-term responders. Combining everolimus and bevacizumab does not distinctly improve response compared to bevacizumab alone, but further study of selected patients with alterations in the PI3K/mTOR pathway may document benefit.


Gender identity and substance use among students in two high schools in Monterrey, Mexico.
This study explored relationships between several hypothesized dimensions of gender identity and substance use outcomes within a non-probability sample of adolescents in Monterrey, Mexico. Based on Mexican concepts of machismo and marianismo, four gender identity constructs were measured: aggressive masculinity, assertive masculinity, affective femininity and submissive femininity. The study assessed how well these gender identity measures predicted substance use behaviors, substance use intentions, expectancies, and normative approval, and exposure and vulnerability to substance offers. Data were drawn from questionnaires completed by 327 students from 2 Monterrey secondary schools. Multivariate ordered logistic and linear regression analyses, adjusted for school level effects, indicated that aggressive masculinity was associated with higher risk of drug use on most outcomes, while affective femininity was associated with lower risk on selected outcomes. Assertive masculinity was associated with only one of the outcomes examined and submissive femininity with none of them. Most gender identity effects persisted after controlling for biological sex, academic performance, age, and other gender identity measures. For two of the outcomes, the gender identity measures had significantly stronger effects for males than for females. The findings are interpreted in light of males' higher risk for drug use and changes in gender roles and gendered behavior that are now occurring in Mexico as in the U.S.


Nora's lesion. Clinical and therapeutic considerations.
In this article we report a case of bizarre paraosteal osteochondromatous proliferation (BPOP), also known as Nora's lesion, arising on the distal phalanx of the fifth finger of the hand in a young-adult subject. In this paper, we discuss the possible therapeutic programme related to the grade of severity of the clinical features and underline the rarity of this lesion and the difficulty of diagnosis, which is exclusively histological.


Effect of CPAP treatment on BP in resistant hypertensive patients according to the BP dipping pattern and the presence of nocturnal hypertension.
High heterogeneity in the blood pressure (BP) response to continuous positive airway pressure (CPAP) exists in patients with resistant hypertension (RH). Only nondipper normotensive and hypertensive patients exhibited BP reductions when treated with CPAP; the baseline BP dipping pattern has been proposed as a predictor of BP response to CPAP but has never been explored in patients with RH. This study aimed to assess the effect of CPAP on BP in subjects with RH with respect to BP dipping pattern or nocturnal hypertension. This is an ancillary study of the SARAH study. RH subjects with an apnea/hypopnea index (AHI) ≥ 15/h and who received CPAP treatment for 1 year were included. Subjects underwent a sleep study and ambulatory BP monitoring (ABPM) at baseline and at the 1-year follow-up. Eighty-nine RH subjects were included. The subjects were mainly male (77.5%) and obese, with a mean age of 66 years (25th-75th percentile; 59.0; 70.0) and an AHI of 32.7/h (25th-75th percentile; 25.0; 54.7). A total of 68.5% of participants were nondippers, and 71.9% had nocturnal hypertension. After 1 year of CPAP, no significant differences in ABPM parameters were observed between dippers and nondippers. According to nighttime BP, subjects with nocturnal normotension did not show significant changes in ABPM parameters, while nocturnal hypertensive subjects achieved a significant reduction in mean nighttime BP of -4.38 mmHg (-7.10 to -1.66). The adjusted difference between groups was 3.04 (-2.25 to 8.34), which was not significant. This study shows that the BP response to CPAP in patients with RH does not differ according to the BP dipping pattern (dipper and nondipper) and suggests a differential response according to the presence of nocturnal hypertension (ClinicalTrials.gov: NCT03002558).


Estimated GFR and Hospital-Acquired Infections Following Major Surgery.
Low estimated glomerular filtration rate (eGFR) increases infection risk, but its contribution to hospital-acquired infection following major surgery is unknown. Retrospective cohort study. Residents of Stockholm, Sweden, 18 years or older with at least 1 recorded serum creatinine measurement, no recent diagnoses of infection, and hospitalized for orthopedic, abdominal, cardiothoracic and vascular, or neurologic surgery between January 2007 and December 2011. EXPOSURES: eGFR<60mL/min/1.73m2 (termed low eGFR) and other clinical comorbid conditions at admission: cancer, cerebrovascular disease, chronic obstructive pulmonary disease (COPD), coronary heart disease, diabetes, heart failure (HF), and liver disease. Incidence and population-attributable fractions of 4 major types of hospital-acquired infections: pneumonia, urinary tract infection, surgical-site infection, and bloodstream infection. Logistic regression analysis. 66,126 patients with a history of orthopedic (n=31,630), abdominal (n=26,317), cardiothoracic and vascular (n=6,266), or neurologic (n=1,913) surgery were studied. Cancer (21%) and low eGFR (18%) were the most prevalent comorbid conditions at admission, followed by diabetes, HF, and COPD (12%). Overall, 3,617 patients (5.5%) had at least 1 type of hospital-acquired infection (1,650 cases of urinary tract infection, 1,196 cases of pneumonia, 635 cases of surgical site infection, and 411 cases of bloodstream infection). The OR of hospital-acquired infection was highest for low eGFR (1.64; 95% CI, 1.51-1.77), followed by HF (1.60; 95% CI, 1.46-1.76), cerebrovascular disease (1.47; 95% CI, 1.34-1.61), cancer (1.43; 95% CI, 1.33-1.55), and COPD (1.37; 95% CI, 1.25-1.50). Low eGFR demonstrated the highest population-attributable fraction for hospital-acquired infections (0.13), followed by cancer (0.10), HF (0.09), and cerebrovascular disease (0.06). When assessed by type of infection, low eGFR particularly contributed to pneumonia (0.15) and urinary tract infection (0.10). Outcome ascertainment based on diagnostic codes. These findings highlight the association between low eGFR and hospital-acquired infection and may inform evidence-based hospital-acquired infection prevention policies following major surgery.


Medium-term outcomes after combined trachelectomy and uterosacral ligament suspension among young women with severe uterine prolapse.
To evaluate anatomic and sexual outcomes among young women with severe pelvic organ prolapse undergoing combined trachelectomy and laparoscopic high uterosacral ligament suspension (LHUS). In a prospective study in Beijing, China, patients (aged ≤50 years) with pelvic organ prolapse of stage III or higher according to the Pelvic Organ Prolapse Quantification (POP-Q) were enrolled between November 2007 and August 2011. After combined trachelectomy and LHUS, patients were followed up at 6 weeks, 6 months, 12 months, and yearly thereafter. Anatomic success was defined as POP-Q lower than stage II. Sexual outcomes were assessed at 6 months via the validated Short-Form Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), and compared with a control group of 39 healthy age-matched women. Among 49 patients, surgical success and patient satisfaction rates were 100% after a median follow-up of 54 months. Among 48 patients who were sexually active at follow-up, 39 (81%) completed the PISQ-12 questionnaire. The 6-month PISQ-12 score was higher than the preoperative score overall (38.1 vs 26.4, P<0.001) and for all three subscale domains (P≤0.001). The PISQ-12 score of postoperative patients was similar to that of control women (36.8, P=0.52). Trachelectomy combined with LHUS produced satisfactory medium-term anatomic and functional outcomes for young women with severe uterine prolapse.


The effects of d- and l-fenfluramine (and their interactions with d-amphetamine) on cortisol secretion.
Twelve normal weight healthy male volunteers participated in a double-blind, placebo-controlled trial of the effects of d- and l-fenfluramine, d-amphetamine, and the interactions between the two isomers of fenfluramine with amphetamine, on cortisol secretion. d-Fenfluramine and d-amphetamine in combination produced the greatest cortisolaemic effect, suggesting that they act by differing neurochemical pathways. d-Fenfluramine produced a significant effect, but l-fenfluramine produced little effect, suggesting that the cortisol-releasing properties of racemic fenfluramine reside in the d-isomer.


Time-resolved X-ray diffraction studies on the effect of slow length changes on tetanized frog skeletal muscle.
1. The mechanism of the enhancement and the deficit of isometric force by slow length changes in frog skeletal muscle was studied with the time-resolved X-ray diffraction technique, using intense X-rays of synchrotron radiation. 2. When a tetanized muscle was slowly stretched by 4% from sarcomere lengths 2.3-2.4 microns, the force rose to a peak during stretch and then decreased to a steady level 10-15% higher than that immediately before stretch. 3. The intensity of the 1,1 equatorial reflection decreased nearly linearly during stretch and then again increased after the completion of stretch, reaching a steady level 12 +/- 5% (mean +/- S.D., n = 11) lower than that immediately before stretch. The above 1,1 intensity change was roughly a mirror image of the force change. 4. The intensity of the 1,0 equatorial reflection showed no marked changes in response to a slow stretch, except for an initial transient increase observed occasionally. 5. If a tetanized muscle was slowly released by 4% from sarcomere lengths 2.3-2.4 microns, the steady force attained after the completion of release was lower than that immediately before release. 6. The 1,1 intensity increased slightly during release, while the 1,0 intensity did not change significantly. 7. The half-width of both the 1,0 and the 1,1 reflections did not change appreciably in response to slow length changes. 8. Slow length changes always produced changes in the spacing between the reflections as expected from the constant-volume behaviour of the myofilament lattice. 9. These results indicate that a slow stretch produces disordering of the myofilament lattice in such a way that the thin filaments are displaced from trigonal positions in the thick filament lattice. The resulting increase in the overall repulsion forces between the filaments may lead to the enhanced isometric force after stretch.


Rapidly Progressive Cardiac Manifestation of Behçet's Disease Involving Conduction System and Aortic Valve.
Cardiac conduction system impairment is a rare clinical manifestation of Behçet's disease. We report a patient who showed 1st degree atrioventricular block at first presentation, and showed aggravated finding of 3rd degree atrioventricular block on five months later. His cardiac manifestation finally developed to acute severe aortic regurgitation on six months later from his first cardiac manifestation. We observed this rapid progression during 6 months and successfully improved symptom and disease severity of the patient with treatment targeting Behçet's disease.


The mimecan gene expressed in human pituitary and regulated by pituitary transcription factor-1 as a marker for diagnosing pituitary tumors.
Mimecan, a secretory protein, belongs to a family of small leucine-rich proteoglycans (SLRPs). The physiological functions of mimecan have not been fully understood. We hypothesize that the mimecan gene expressed in the human pituitary and regulated by pituitary transcription factor-1 (Pit-1) might act as a marker for diagnosing pituitary tumors. The clinical aspect of our work was a cross-sectional study. In total, 20 pituitary tumor samples were collected from January 1, 2002, to December 30, 2002, in Ruijin Hospital, Shanghai, China. The number of pituitary tumors was limited. Collection of more pituitary tumor samples for additional observation will be necessary. The main outcomes were measured by Northern blot, in situ hybridization, immunohistochemical analysis, and so on. The mimecan gene was expressed at a moderate level in the mouse pituitary gland by Northern blot analysis. Expression of mimecan mRNA and protein is also observed in the human anterior pituitary gland. Luciferase reporter analysis and electrophoretic mobility shift assays show that Pit-1 activates the human mimecan promoter through Pit-1 response element sites. In addition, our data also show that almost all the ACTH- or GH-positive pituitary tumors likely express mimecan protein, and only a portion of prolactin-, TSH-, FSH-, and LH-positive pituitary tumors express mimecan protein. This work provides insight into the regulating mechanism of mimecan in pituitary and suggests that mimecan may be an unidentified pituitary secretory protein, and certain pituitary cells secreting ACTH or GH also secrete mimecan.


Peroxisome proliferator-activated receptor alpha induces rat sterol carrier protein x promoter activity through two peroxisome proliferator-response elements.
Sterol carrier protein x (SCPx) plays a critical role in the peroxisomal oxidation of fatty acids. It has been previously demonstrated in streptozotocin-induced diabetic rats that SCPx expression is induced in association with an elevation in serum fatty acid and triglyceride levels. To elucidate the mechanisms underlying the expression of this gene during diabetes, the rat SCPx promoter was cloned and analyzed for regulatory motifs. Sequence analysis of this TATA-less promoter revealed two putative peroxisomal-proliferator-response element (PPRE) binding motifs at positions -134 and -869 relative to the translation start site. To examine peroxisomal-proliferator-activated receptor alpha (PPARalpha) effects on this gene, 935 bp of the SCPx promoter containing both PPRE motifs was cloned in front of the chloramphenicol acetyl-transferase gene or the luciferase gene and co-transfected into HTB-9 cells with vectors that encoded for PPARalpha and retinoid X receptor (RXR). The results indicate that PPARalpha was able to induce SCPx promoter activity in both cases, an effect that was enhanced by RXR and clofibrate. In addition, mutational analysis studies demonstrated that both PPREs contributed to the PPARalpha/RXRalpha-dependent activation of the SCPx promoter. Mobility shift assays and supershift analysis showed that nuclear extracts containing PPARalpha bound to the two PPRE motifs. This investigation indicates that similar to other genes involved in beta-oxidation, SCPx transcription may be controlled by fatty acid levels via PPARalpha.


Hirschsprung disease and Down syndrome: From the reappraisal of risk factors to the impact of surgery.
The association of Hirschsprung disease (HSCR) and Down Syndrome (DS) is not uncommon (HSCR+DS). This paper aims at reporting the results of a 24-year series focusing on surgical approach, complications and long term outcome. The notes of all patients admitted with a diagnosis of HSCR+DS have been retrospectively reviewed. Surgical details, intraoperative complications, long term issues and functional outcome have been recorded. The results have been compared to those of patients without DS and were assessed based on surgical approach. A total of 23 HSCR+DS out of a series of 385 HSCR (6%) have been included. Preoperative enterocolitis (HAEC) was reported by 32%. Associated anomalies were detected in more than half of the patients. In particular, Congenital Heart Defects (CHDs) were reported by 57%. Postoperative complications (mostly symptomatic anal sphincter achalasia) were experienced by 55%. Constipation was experienced by 30%; severe continence issues, by 53%. One patient suffering from severe CHDs died. With regard to complications, only symptomatic anal achalasia requiring intrasphincteric BoTox injection was significantly more frequent in HSCR+DS (30% vs 10%, p = 0.0071). Similarly, continence proved to be significantly worse in HSCR+DS. With the exception of symptomatic anal achalasia, HSCR+DS patients proved not to have a higher likelihood of complications compared to HSCR alone. On the other hand, functional results in the long term are worse. As a consequence, long term follow up and personalized rehabilitation programs are warranted for this delicate subset of HSCR patients. Level III.


Altered grooming responses to stress in rats exposed prenatally to ethanol.
The effects of prenatal alcohol exposure on grooming, locomotion, and rearing in response to stress were examined in adult rats whose mothers consumed a liquid diet containing 35% ethanol-derived calories (EDC). Offspring of both pair-fed 0% EDC mothers and ad libitum chow-fed mothers were included as controls. In Experiment 1, females groomed more than males following placement into a novel test chamber, but no differences due to prenatal treatment were observed. Ethanol-exposed animals groomed more than controls following the stress of a forced 1-min swim (Experiment 2), but when rats tested in Experiment 1 were observed again after forced swim stress (Experiment 3), no differences due to prenatal treatment or sex were observed. Experiment 4 examined the effects of pretreatment with 1 mg/kg naloxone on novelty-induced grooming and as in Experiment 1 prenatal treatment did not affect grooming responses. Females again groomed significantly more than males and naloxone reduced grooming equally for all groups. The results suggest that novelty-induced grooming is a sex-influenced behavior, with females grooming more than males, and that animals exposed prenatally to alcohol and tested as adults may have altered responses to certain stressors (i.e., forced swim) under specific conditions. The altered grooming response of alcohol-exposed rats to swim stress can be eliminated by preexposing them to novelty stress.


The dualistic role of the purinergic P2Y12-receptor in an in vivo model of Parkinson's disease: Signalling pathway and novel therapeutic targets.
Parkinson's disease (PD) is a chronic, progressive neurodegenerative condition; characterized with the degeneration of the nigrostriatal dopaminergic pathway and neuroinflammation. During PD progression, microglia, the resident immune cells in the central nervous system (CNS) display altered activity, but their role in maintaining PD development has remained unclear to date. The purinergic P2Y12-receptor (P2Y12R), which is expressed on the microglia in the CNS has been shown to regulate microglial activity and responses; however, the function of the P2Y12R in PD is unknown. Here we show that MPTP-induced PD symptoms in mice are associated with marked neuroinflammatory changes and P2Y12R contribute to the activation of microglia and progression of the disease. Surprisingly, while pharmacological or genetic targeting of the P2Y12R augments acute mortality in MPTP-treated mice, these interventions protect against the neurodegenerative cell loss and the development of neuroinflammation in vivo. Pharmacological inhibition of receptors during disease development reverses the symptoms of PD and halts disease progression. We found that P2Y12R regulates ROCK and p38 MAPK activity and control cytokine production. Our principal finding is that the receptor has a dualistic role in PD: functional P2Y12Rs are essential to initiate a protective inflammatory response, since the lack of the receptor leads to reduced survival; however, at later stages of neurodegeneration, P2Y12Rs are apparently responsible for maintaining the activated state of microglia and stimulating pro-inflammatory cytokine response. Understanding protective and detrimental P2Y12R-mediated actions in the CNS may reveal novel approaches to control neuroinflammation and modify disease progression in PD.


Dose evaluation of inter- and intra-fraction prostate motion in extremely hypofractionated intensity-modulated proton therapy for prostate cancer.
Inter- and intra-fractional prostate motion can deteriorate the dose distribution in extremely hypofractionated intensity-modulated proton therapy. We used verification CTs and prostate motion data calculated from 1024 intra-fractional prostate motion records to develop a voxel-wise based 4-dimensional method, which had a time resolution of 1 s, to assess the dose impact of prostate motion. An example of 100 fractional simulations revealed that motion had minimal impact on planning dose, the accumulated dose in 95 % of the scenarios fulfilled the clinical goals for target coverage (D95 > 37.5 Gy). This method can serve as a complementary measure in clinical setting to guarantee plan quality.


High salt-induced PSI-supercomplex is associated with high CEF and attenuation of state transitions.
While PSI-driven cyclic electron flow (CEF) and assembly of thylakoid supercomplexes have been described in model organisms like Chlamydomonas reinhardtii, open questions remain regarding their contributions to survival under long-term stress. The Antarctic halophyte, C. priscuii UWO241 (UWO241), possesses constitutive high CEF rates and a stable PSI-supercomplex as a consequence of adaptation to permanent low temperatures and high salinity. To understand whether CEF represents a broader acclimation strategy to short- and long-term stress, we compared high salt acclimation between the halotolerant UWO241, the salt-sensitive model, C. reinhardtii, and a moderately halotolerant Antarctic green alga, C. sp. ICE-MDV (ICE-MDV). CEF was activated under high salt and associated with increased non-photochemical quenching in all three Chlamydomonas species. Furthermore, high salt-acclimated cells of either strain formed a PSI-supercomplex, while state transition capacity was attenuated. How the CEF-associated PSI-supercomplex interferes with state transition response is not yet known. We present a model for interaction between PSI-supercomplex formation, state transitions, and the important role of CEF for survival during long-term exposure to high salt.


Dominican amber net-winged beetles suggest stable paleoenvironment as a driver for conserved morphology in a paedomorphic lineage.
Paedomorphosis is a heterochronic syndrome in which adult individuals display features of their immature forms. In beetles, this phenomenon occurs widely in the superfamily Elateroidea, including the net-winged beetles (Lycidae), and, due to the usual flightlessness of paedomorphic females, it is hypothesized to cause speciation rates higher than in non-paedomorphic lineages. However, some fossils of paedomorphic lycids do not support this with palaeobiological data. Discovery of new Lycidae fossils attributed to the West Indian extant paedomorphic genus Cessator Kazantsev in the Dominican amber also suggests morphological stasis within this genus in the Greater Antilles. We describe Cessator anachronicus Ferreira and Ivie, sp. nov. based on adult males, as well as the first ever recorded fossil net-winged beetle larva of the same genus. We propose that the relatively young age of the studied fossils combined with the stable conditions in the forest floor of the Greater Antilles through the last tens of million years could explain the exceptionally conserved morphology in the net-winged beetles affected by the paedomorphic syndrome.


Quartz crystal analytical sensors: the future of label-free, real-time diagnostics?
Acoustic sensor technologies have a long and prestigious history. However, liquid phase applications based upon thickness shear mode transducers are a relatively recent addition but are nonetheless being rapidly accepted as a broad usage analytical platform upon which to carry out label-free, real-time chemical, biological and pharmaceutical assays. This article discusses the development of thickness shear mode devices, current technologies, with a focus on the breadth of application and the future potential of the technique within the pharmaceutical and biochemical industries.


Modified hindfoot alignment radiological evaluation and application in the assessment of flatfoot.
Alignment is indispensable for the foot and ankle function, especially in the hindfoot alignment. In the preoperative planning of patients with varus or valgus deformity, the precise measurement of the hindfoot alignment is important. A new method of photographing and measuring hindfoot alignment based on X-ray was proposed in this study, and it was applied in the assessment of flatfoot. This study included 28 patients (40 feet) with flatfeet and 20 volunteers (40 feet) from January to December 2018. The hindfoot alignment shooting stand independently designed by our department was used to take hindfoot alignment X-rays at 10 degree, 15 degree, 20 degree, 25 degree, and 30 degree. We measured the modified tibio-hindfoot angle (THA) at the standard hindfoot aligment position (shooting at 20 degree) and evaluated consistency with the van Dijk method and the modified van Dijk method. In addition, we observed the visibility of the tibiotalar joint space from all imaging data at five projection angles and evaluated the consistency of the modified THA method at different projection angles. The angle of hindfoot valgus of flatfoot patients was measured using the modified THA method. The mean THA in the standard hindfoot aligment view in normal people was significantly different among the three evaluation methods (P < .001). The results from the modified THA method were significantly larger than those from the Van Dijk method (P < .001) and modified Van Dijk method (P < .001). There was no significant difference between the results of the modified THA method and the weightbearing CT (P = .605), and the intra- and intergroup consistency were the highest in the modified THA group. The tibiotalar space in the normal group was visible in all cases at 10 degree, 15 degree, and 20 degree; visible in some cases at 25 degree; and not visible in all cases at 30 degree. In the flatfoot group, the tibiotalar space was visible in all cases at 10 degree, visible in some cases at 15 degree and 20 degree, and not visible in all cases at 25 degree and 30 degree. In the normal group, the modified THA was 4.84 ± 1.81 degree at 10 degree, 4.96 ± 1.77 degree at 15 degree, and 4.94 ± 2.04 degree at 20 degree. No significant differences were found among the three groups (P = .616). In the flatfoot group, the modified THA of 18 feet, which was visible at 10 degree, 15 degree and 20 degree, was 13.58 ± 3.57 degree at 10 degree, 13.62 ± 3.83 degree at 15 degree and 13.38 ± 4.06 degree at 20 degree. There were no significant differences among the three groups (P = .425). The modified THA evaluation method is simple to use and has high inter- and intragroup consistency. It can be used to evaluate hindfoot alignment. For patients with flatfeet, the 10 degree position view and modified THA measurement can be used to evaluate hindfoot valgus.


Telemedicine (virtual clinic) effectively delivers the required healthcare service for pediatric ambulatory surgical patients during the current era of COVID-19 pandemic: A mixed descriptive study.
Children often suffer from congenital or acquired diseases. Ambulatory cases represent the vast majority of pediatric surgical cases. COVID-19 pandemic-associated regulatory precautions had made the process of seeking medical advice at a suitable appointment such a big problem. We utilized telemedicine (online encounter) to deliver the required healthcare service for sorting and guiding pediatric ambulatory surgical patients. In this article, we aimed to: (1) present our experience, (2) evaluate the effectiveness, and (3) document the results of this technology to solve the problem of difficult healthcare accessibility. In this study, we compared the utilization of telemedicine (virtual clinic via video consultation) prospectively in the current era of the COVID-19 pandemic in the period from June 2020 to July 2021 to the in-person clinic encounter at the outpatient department (OPD) retrospectively in the previous year (from June 2019 until the end of May 2020) for perioperative management of pediatric ambulatory surgical patients. The study was conducted at 3 tertiary care pediatric surgery centers. The information recorded for analysis included: demographic data, surgical condition distribution, time interval from the appointment request till the actual encounter with the surgeon, conversation duration, distance traveled, and ultimate fate of the consultations. For both groups, service was evaluated after the first follow-up visit by a patient survey questionnaire (Patient Experience Assessment form) including questions relevant to each encounter. A total of 1124 pediatric patients with various ambulatory surgical conditions had been scheduled for virtual clinic video encounters. Of them, 1056 cases were evaluated by video consultation, supervised by their parents or caregivers, thus, achieving an attendance rate of 94%. Of the remaining cases, 2% (n = 23) were canceled and 4% (n = 45) did not attend the virtual clinic. Two-thirds of the cases live in rural /remote areas. Patients' overall satisfaction was 92%. This was in comparison to 872 pediatric ambulatory surgical patients scheduled for in-person clinic visits before the implementation of the virtual clinic. Of them, only 340 cases had attended the clinic, thus, achieving an attendance rate of 39%. Of the remaining cases, 450 cases (51.6%) were canceled and 82 cases (9.4%) did not attend the clinic (no show). About 48% of the cases live in rural areas. For this group, patients' overall satisfaction was 63%. The mean encounter duration was similar for both groups (∼ 5 min). Surgical condition distribution was also similar (p-value: 0.694). For new cases, the time interval from appointment request till the actual encounter was very short for the virtual clinic group (range: 6-15 days) as compared to the in-person clinic group (range: 30-180 days). Patients were followed up for a median period of 14 ± 3.25 months (range: 6-22 months) with no patient loss to follow-up. Telemedicine can effectively bridge the patient-physician communication gap caused by the regulatory precautions mandated by the current COVID-19 pandemic. It achieved an attendance rate of 94% and parents' / patients' overall satisfaction of 92%.


Global Delivery of Human Papillomavirus Vaccines.
Worldwide, cervical cancer is the fourth most common cancer among women. Human papillomavirus (HPV) vaccination, if broadly implemented, has the potential to significantly reduce global rates of morbidity and mortality associated with cervical and other HPV-related cancers. More than 100 countries around the world have licensed HPV vaccines. As of February, 2015, there were an estimated 80 national HPV immunization programs and 37 pilot programs. This article discusses global implementation of HPV vaccination programs and issues such as vaccine financing and different approaches to HPV vaccine delivery.


Birth prevalence of neural tube defects in eastern Africa: a systematic review and meta-analysis.
Neural tube defects (NTDs) are associated with high rates of neonatal mortality and morbidity worldwide. The promotion of folic acid fortification and supplementation in pregnant women by the Food and Drug Administration significantly decreased the incidence of NTDs in the United States. This practice is not widely adopted in Eastern Africa countries. We hypothesized that these countries experience a higher burden of NTDs than countries that promote the use of folic acid. We aimed to estimate the birth prevalence of NTDs in the United Nations (UN) Eastern African region. PubMed (Medline), Embase, and Cochrane Library databases were systematically searched from inception to December 17, 2021. We included randomized controlled trials or observational studies that reported the prevalence estimates of NTDs in Eastern Africa. Random effects model was used to pool the effect estimates. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess the certainty of the evidence. Outcome measures were overall and specific (spina bifida, anencephaly, encephalocele) rates of NTDs per 10,000 births, including live and stillborn cases. The meta-analysis included 20 studies consisting of 752,936 individuals. The pooled prevalence of all NTDs per 10,000 births in Eastern Africa was 33.30 (95% CI: 21.58 to 51.34). Between-study heterogeneity was high (I2 = 97%, p < 0.0001), The rate was highest in Ethiopia (60 per 10,000). Birth prevalence of spina bifida (20 per 10,000) was higher than anencephaly (9 per 10,000) and encephalocele (2.33 per 10,000). No studies on NTDs were identified in 70% of the UN Eastern Africa region. Birth prevalence increased by 4% per year from 1983 to 2018. The level of evidence as qualified with GRADE was moderate. The birth prevalence of NTDs in the United Nations region of Eastern Africa is 5 times as high as observed in Western countries with mandatory folic acid supplementation in place. Therefore, mandatory folic acid supplementation of stable foods may decrease the risk of NTDs in Eastern Africa.


Evaluation of retroperitoneum with computerized tomography and ultrasonography in patients with testicular tumors.
Results of CT and US examinations in 24 patients with testicular tumors yielded similar sensitivity and specificity in the diagnosis of enlarged retroperitoneal lymph nodes found at laparatomy. Therefore, the choice of either imaging modality may be influenced by other factors such as presence of abundant bowel gas, post-operative wounds, surgical clips in the abdomen, cachexia or obesity.


Plasma glucose, lactate, sodium, and potassium levels in children hospitalized with acute alcohol intoxication.
The aim of our research was to study prevalence of changes in plasma levels of lactate, potassium, glucose, and sodium in relation to alcohol concentration in children hospitalized with acute alcohol intoxication (AAI). Data from 194 under 18-year-old children hospitalized to the two only children's hospital in Estonia over a 2-year period were analyzed. The pediatrician on call filled in a special form on the clinical symptoms of AAI; a blood sample was drawn for biochemical tests, and a urine sample taken to exclude narcotic intoxication. The most common finding was hyperlactinemia occurring in 66% of the patients (n=128) followed by hypokalemia (<3.5 mmol/L) in 50% (n=97), and glucose above of reference value (>6.1 mmol/L) in 40.2% of the children (n=78). Hypernatremia was present in five children. In conclusion, hyperlactinemia, hypokalemia, and glucose levels above of reference value are common biochemical findings in children hospitalized with acute AAI.


Composites based on zirconia and transition metal oxides for osteosarcoma treatment. Design, structural, magnetic and mechanical evaluation.
The formation of structurally stable composites of cubic zirconia (c-ZrO2) with selective transition metal oxides (α-Fe2O3, Mn3O4, NiO, Co3O4) is investigated. The results affirm the prospect to retain unique c-ZrO2 and transition metal oxide (TMO) structures in the composite form until 1400 °C. It is also shown that 30 mol% Y2O3 possess the ability to retain stable c-ZrO2 despite the existence of assorted TMO content in the composites. The elemental states of Fe3+, Mn2+/4+, Ni2+ and Co2+/3+ are confirmed from the corresponding α-Fe2O3, Mn3O4, NiO, and Co3O4. The magnetic properties are highly influenced by the quantity of TMO component while the c-ZrO2 plays a decisive role in the resultant mechanical properties. The wide range of properties delivered by the composites extends the possibility to probe for osteosarcoma treatment that demands optimal mechanical and magnetic features.