Synthesis of cyclic ADP-carbocylcic-xylose and its 3"-O-methyl analogue as stable and potent Ca2+ -mobilizing agents.
We previously showed that 3"-deoxy-cyclic ADP-carbocyclic-ribose (3"-deoxy-cADPcR, 3) is a stable and highly potent analogue of cyclic ADP-ribose (cADPR, 1), a Ca2+ -mobilizing second messenger. From these results, we newly designed another 3"-modified analogues of cADPcR and identified the N1-"xylo"-type carbocyclic analogue, i.e., cADPcX (4), as one of the most potent cADPR-related compounds reported so far.


Perceptions and attitudes around perinatal mental health in Bangladesh, India and Pakistan: a systematic review of qualitative data.
Perinatal mental health (PMH) is a worldwide public health issue crossing cultural boundaries. However, the prevalence of PMH conditions vary considerably. These disparities stem in part from poor understanding and stigma surrounding PMH which hinder pregnant women from seeking mental health care and may exacerbate their conditions. Bangladesh, India and Pakistan are South Asian countries with a higher burden of PMH conditions than in the Global North-West and very different social and cultural norms around gender and mental health. The aim of this systematic review (PROSPERO Ref: CRD42020167903) was to identify, synthesise and appraise the available literature on perceptions and attitudes of perinatal (pregnant and postpartum) women, their families and healthcare providers surrounding PMH in Bangladesh, India and Pakistan. Five electronic databases, MEDLINE, Embase, PsycINFO, Scopus and Web of science, and grey literature were searched using predefined search terms. Qualitative or quantitative articles with a qualitative component reporting perceptions and attitudes surrounding PMH in Bangladesh, India and Pakistan were eligible for inclusion, if published in English between January 2000 and January 2021. The Critical Appraisal Skills Programme Qualitative Research Checklist and Newcastle-Ottawa Scale for cross-sectional studies were used to assess study quality. Findings were synthesised using thematic synthesis, as described by Thomas and Harden 2008. Eight studies were included. Five overarching themes comprising 17 sub-categories were identified. These descriptive themes were: perceived causes of PMH, perceived symptoms of PMH, perceptions of motherhood, accessing PMH care and emotional sharing and coping strategies. Sociocultural expectations underpin many of the themes identified in this review including the importance of familial and societal causes of PMH, emphasis on physical symptoms, sacredness of motherhood, lack of awareness, stigma, shame, limited resources allocated for mental health and lack of emotional sharing. There is a complex range of perceptions and attitudes around PMH which influence women's experiences and access to PMH care. These findings will inform policy and practice through targeted interventions to tackle stigmatising attitudes and increasing education and training for healthcare providers.


New insights on possible vaccine development against SARS-CoV-2.
In December 2019, a novel virus, namely COVID-19 caused by SARS-CoV-2, developed from Wuhan, (Hubei territory of China) used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Data revealed that the newly emerged SARS-CoV-2 affected more than 24,854,140 people with 838,924 deaths worldwide. Until now, no licensed immunization or drugs are present for the medication of SARS-CoV-2. The present review aims to investigate the latest developments and discuss the candidate antibodies in different vaccine categories to develop a reliable and efficient vaccine against SARS-CoV-2 in a short time duration. Besides, the review focus on the present challenges and future directions, structure, and mechanism of SARS-CoV-2 for a better understanding. Based on data, we revealed that most of the vaccines are focus on targeting the spike protein (S) of COVID-19 to neutralized viral infection and develop long-lasting immunity. Up to phase-1 clinical trials, some vaccines showed the specific antigen-receptor T-cell response, elicit the humoral and immune response, displayed tight binding with human-leukocytes-antigen (HLA), and recognized specific antibodies to provoke long-lasting immunity against SARS-CoV-2.


Failure rates and survival times of systemic and biologic therapies in treating psoriasis: a retrospective study.
Systemic and biologic therapies have varying failure rates and survival times in treating psoriasis. We aim to describe the patterns of therapy failure in psoriasis patients. A retrospective (January 2009 to May 2018) analysis of 250 psoriasis patients seen at a psoriasis referral center, and 806 treatment courses of several systemic and biologic therapies, was conducted to determine failure rates and survival times for systemic and biologic therapies. Systemic therapies failed more often due to their adverse effects (16.4% vs 7.2%, p < .001). Biologics failed more often due to secondary failure (24.2% vs. 9.3%, p < .001). Biologics had a longer survival time (23.9 ± 22.2 vs. 12.6 ± 15.4 months, p < .001), even with early failures (≤6 months) removed (29.0 ± 22.5 vs. 21.1 ± 16.4 months, p = .014). Tertiary referral center, unreported causes of failure, sample size. Systemic therapies fail more often due to adverse effects while biologics fail more often due to loss of efficacy. Biologic therapies have longer survival times than systemic therapies.


Porcine epidemic diarrhea virus 3CLpro causes apoptosis and collapse of mitochondrial membrane potential requiring its protease activity and signaling through MAVS.
Porcine epidemic diarrhea (PED) is a highly contagious and virulent intestinal infectious disease characterized by diarrhea, vomiting and dehydration. Although PEDV-induced apoptosis has been characterized in vitro and vivo, the functional proteins related to this event and the mechanism still need further research. Here, we firstly demonstrated that PEDV epidemic strain JS2013 could trigger apoptosis in a dose- and time-dependent manner. Then, PEDV 3CLpro was further identified as a crucial inducer of PEDV-triggered apoptosis. In addition, using site-directed mutagenesis to disrupt the protease activity of 3CLpro by His41 and Cys144 mutations, we found that 3CLpro-induced apoptosis and mitochondrial damage significantly reduced, suggesting that the protease activity of 3CLpro was essential for apoptosis and mitochondrial damage. Furthermore, PEDV 3CLpro could synergistically promote MAVS-mediated apoptosis and MAVS was involved in the signaling pathway of 3CLpro-induced apoptosis, but no direct interaction between PEDV 3CLpro and MAVS was detected by immunoprecipitation assays. Our findings provide important insights into the role of 3CLpro in the pathogenicity of PEDV.


Change in metabolic turnover is an alternate mechanism increasing cell surface epidermal growth factor receptor levels in tumor cells.
The biosynthesis and metabolic turnover of the epidermal growth factor (EGF) receptor was examined in a human pancreatic carcinoma cell line, UCVA-1. This cell line has been shown to possess a much higher level of EGF receptors than is expected solely from receptor gene/mRNA dosage. Analysis of the biosynthesis using metabolic labeling, immunological quantitation, and inhibitor treatment revealed that the naked EGF receptor in UCVA-1 cells is a protein of Mr 130,000 that is matured consecutively as a Mr 160,000 and 170,000 glycoprotein through post-translational glycosylation. Analysis of the metabolic turnover using pulse-chase labeling and inhibitor treatment revealed that the rate of EGF receptor synthesis in UCVA-1 cells was similar to that in two squamous cell carcinoma cell lines, NA and Ca9-22, which also have high numbers of EGF receptors, but because of gene amplification. In contrast, the rate of receptor degradation in UCVA-1 cells was significantly slower than in the other two cell lines. These results suggest that the retarded metabolic turnover may constitute a unique mechanism for elevating cell surface EGF receptor levels in some tumor cells independent of gene amplification.


Myristoylated src-oncogene products are potently detected by the monoclonal antibody to the NH2-terminal myristoyl-Gly-Ser-Ser-Lys src-peptide.
Monoclonal antibodies were raised against a synthetic NH2-terminal myristoyl tetrapeptide (N-myristoyl-Gly-Ser-Ser-Lys) which is characteristic of an NH2-terminal portion of pp60src, the transforming protein of src-oncogene. The antibody reacted with the albumin conjugated with both the N-myristoyl and N-lauroyl-tetrapeptides, but concentrations at which 50% of the immunoreaction was inhibited were 5 pmol for the N-myristoyl and 830 pmol for N-lauroyl tetrapeptidyl albumin. On the other hand, N-palmitoyl tetrapeptidyl and underivatized albumin, and Gly-Ser-Ser-Lys-Ser-Lys-Pro-Lys octapeptide had no effects. These results suggest a high affinity of the antibody for an N-myristoyl-Gly-Ser-Ser-Lys moiety. src-Oncogene products in Rous sarcoma virus-transformed cells and human colon carcinoma tumor cells were selectively identified as myristoylated pp60src by immunoprecipitation analyses with the antibody.


An analytical, variable resolution, complete description of static molecules and their intermolecular binding properties.
A fully analytical description of molecular shape, as defined by the shrink-wrap isodensity or solvent-excluded surfaces and local properties related to Coulomb, donor/acceptor, and polarizability (dispersion) interactions is described. The molecular surface and four local properties adequate for describing intermolecular interactions (the molecular electrostatic potential and the local ionization energy, electron affinity, and polarizability) are fitted to spherical-harmonic expansions, which provide a compact and information-rich description of the properties of the static molecule. The resolution of the description can be varied from isotropic to near atomistic detail by adjusting the order of the individual spherical-harmonic expansions. Examples are given to illustrate the effect of truncating the different spherical-harmonic approximations.


Incidental Hamartoma in an elderly patient: a case report.
Neuromuscular hamartoma is a very rare tumor; with only five cases reported in the orbit. It often occurs in infants and young children and involves large peripheral nerves, but there has been only few reports of occurrence in the orbit and adults. This paper describes a 70-year-old man with an incidental orbital mass detected by an imaging test and who later developed associated symptoms. The mass was diagnosed as neuromuscular hamartoma. Superior rectus muscle recession and inferior rectus muscle resection were performed in the right eye for hypertropia secondary to postoperative inferior rectus muscle palsy. Hypertropia in the right eye and diplopia improved after surgery, and regular follow-up is underway. This is the first case of an incidentally detected orbital mass diagnosed by histologic examination as a neuromuscular hamartoma in an older patient whose proptosis progressed after a long period of inactivity.


Impact of gestational diabetes mellitus treatment on medium/long-term outcomes after pregnancy: A systematic review and meta-analysis.
We aimed to evaluate the effect of gestational diabetes mellitus (GDM) treatment on medium/long-term outcomes both the mother and offspring. We performed a systematic review on randomized clinical trials addressing specific treatment of women with GDM versus usual care and its impact on maternal and offspring outcomes at medium/long-term. MEDLINE, EMBASE and CENTRAL were searched from inception to 8 October 2021. maternal (diabetes, metabolic syndrome, 12 secondary); offspring (diabetes, impaired fasting glucose, impaired glucose tolerance, high body mass index, 15 secondary). Risk of bias was assessed with Cochrane tool and aggregation performed with Revman 5.4. We included five studies (1140 women, 767 offspring) with follow-up ranging 4-16 years after delivery. GDM treatment likely does not reduce risk of maternal diabetes (RR 1.00; [95% CI 0.82-1.23]) and may not reduce that of metabolic syndrome (RR 0.93; [95% CI 0.71-1.22]). We obtained very uncertain evidence that treatment may increase maternal HDL-cholesterol. Findings showed that GDM treatment may not have an impact on infants' outcomes (RRs 0.79; [95% CI 0.39-1.69] for impaired fasting glucose; RR 0.91; [95% CI 0.74-1.12] for body mass index >85th centile and 0.89; [95% CI 0.65-1.22] for body mass index >95th centile respectively). With current evidence is uncertain if specific treatment of women with GDM has an impact on medium/long-term metabolic outcomes either in the mother or in the offspring. These results add evidence to the recommendation of systematically reevaluating mother and offspring after delivery. OSF, DOI 10.17605/OSF.IO/KFN79.


Developmental appearance of dentin matrix protein 1 during the early dentinogenesis in rat molars as identified by high-resolution immunocytochemistry.
Dentin matrix protein 1 (DMP 1) is an acidic phosphoprotein that has been postulated to play an important role in mineralized tissue formation. We have examined rat molar tooth germs by applying a high-resolution immunocytochemical approach with the purpose to identify the temporal and spatial localization of DMP 1 at the onset of dentinogenesis. Upper molar tooth germs of 2- to 3-day-old Wistar rats were fixed in a cacodylate-buffered 0.1% glutaraldehyde + 4% formaldehyde fixative, left unosmicated and embedded in LR White resin. The sections were incubated with a polyclonal DMP 1 antibody for postembedding colloidal gold immunolabeling and examined in a Jeol 1010 transmission electron microscope. The earliest localization of DMP 1 was in the Golgi region as well as in the nucleus of differentiating odontoblasts. When mineralization spread from matrix vesicles to the surrounding matrix, DMP 1 was extracellularly detected around the mineralizing globules. In the regions of fully mineralized mantle dentin, it was present in the mineralized regions, mainly around the peritubular dentin. The appearance of DMP 1 during early dentinogenesis implies a direct role for this protein in both odontoblast differentiation and matrix mineralization.


Cold-Responsive Nanoparticle Enables Intracellular Delivery and Rapid Release of Trehalose for Organic-Solvent-Free Cryopreservation.
Conventional cryopreservation of mammalian cells requires the use of toxic organic solvents (e.g., dimethyl sulfoxide) as cryoprotectants. Consequently, the cryopreserved cells must undergo a tedious washing procedure to remove the organic solvents for their further applications in cell-based medicine, and many of the precious cells may be lost or killed during the procedure. Trehalose has been explored as a nontoxic alternative to traditional cryoprotectants. However, mammalian cells do not synthesize trehalose or express trehalose transporters in their membranes, and the lack of an approach for the efficient intracellular delivery of trehalose has been a major hurdle for its use in cell cryopreservation. In this study, a cold-responsive polymer (poly(N-isopropylacrylamide-co-butyl acrylate)) is utilized to synthesize nanoparticles for the encapsulation and intracellular delivery of trehalose. The trehalose-laden nanoparticles can be efficiently taken up by mammalian cells. The nanoparticles quickly and irreversibly disassemble upon cold treatment, enabling the controlled and rapid release of trehalose from the nanoparticles inside cells. The latter is confirmed by an evident increase in cell volume upon cold treatment. This rapid cold-triggered intracellular release of trehalose is crucial to developing a fast protocol to cryopreserve cells using trehalose. Cells with intracellular trehalose delivered using the nanoparticles show comparable postcryopreservation viability compared to that of cells treated with DMSO, eliminating the need for the tedious and cell-damaging washing procedure required for using the DMSO-cryopreserved cells in vivo. This cold-responsive nanoparticle may greatly facilitate the use of trehalose as a nontoxic cryoprotectant for banking cells and tissues to meet their high demand by modern cell-based medicine.


Evaluation of misdiagnosed cases of subarachnoid hemorrhage and causal factors for misdiagnosis.
Diagnosis has a major impact on the outcome of subarachnoid hemorrhage (SAH). We studied patients with SAH who were admitted to our hospital in an effort to identify ways to prevent misdiagnosis. A total of 494 patients with SAH were admitted to the Department of Neurosurgery from 2003 through 2010. Misdiagnosis occurred in 30 patients (6.1%). We studied the symptoms and the types of misdiagnoses in these 30 patients. Misdiagnosis occurred 37 times in the 30 patients (6 patients were given more than 1 misdiagnosis). There were 3 types of misdiagnoses. Type 1 cases were misdiagnosed as a common cold, type 2 cases were misdiagnosed as circulatory organ disease, and type 3 cases were misdiagnosed as digestive organ disease. Type 1 cases were mild, and diagnosis required detailed medical history analyses. Type 2 cases were severe and were diagnosed based on electrocardiographic and echocardiographic changes characteristic of SAH. Symptoms of type 3 cases included vomiting, and diagnosis required recognition of meningeal irritation syndrome and detailed medical history analyses.


The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke.
Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines. Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.


Plasma-Based Measurements of Tumor Heterogeneity Correlate with Clinical Outcomes in Metastatic Colorectal Cancer.
Sequencing circulating tumor DNA (ctDNA) from liquid biopsies may better assess tumor heterogeneity than limited sampling of tumor tissue. Here, we explore ctDNA-based heterogeneity and its correlation with treatment outcome in STEAM, which assessed efficacy and safety of concurrent and sequential FOLFOXIRI-bevacizumab (BEV) vs. FOLFOX-BEV for first-line treatment of metastatic colorectal cancer. We sequenced 146 pre-induction and 89 post-induction patient plasmas with a 198-kilobase capture-based assay, and applied Mutant-Allele Tumor Heterogeneity (MATH), a traditionally tissue-based calculation of allele frequency distribution, on somatic mutations detected in plasma. Higher levels of MATH, particularly in the post-induction sample, were associated with shorter progression-free survival (PFS). Patients with high MATH vs. low MATH in post-induction plasma had shorter PFS (7.2 vs. 11.7 months; hazard ratio, 3.23; 95% confidence interval, 1.85−5.63; log-rank p < 0.0001). These results suggest ctDNA-based tumor heterogeneity may have potential prognostic value in metastatic cancers.


Dose correction for post-contrast T1 mapping of the heart: the MESA study.
Post-contrast myocardial T1 (T1(myo,c)) values have been shown to be sensitive to myocardial fibrosis. Recent studies have shown differences in results obtained from T1(myo,c) and extracellular volume fraction (ECV) with respect to percentage fibrosis. By exploring the relationship between blood plasma volume and T1(myo,c), the underlying basis for the divergence can be explained. Furthermore, dose administration based on body mass index (BMI), age and gender can mitigate the divergence in results. Inter-subject comparison of T1(myo,c) required adjustment for dose (in mmol/kg), time and glomerular filtration rate. Further adjustment for effective dose based on lean muscle mass reflected by blood/plasma volume was performed. A test case of 605 subjects from the MESA study who had undergone pre- and post-contrast T1 mapping was studied. T1(myo,c) values were compared between subjects with and without metabolic syndrome (MetS), between smoking and non-smoking subjects, and subjects with and without impaired glucose tolerance, before and after dose adjustment based on plasma volume. Comparison with ECV (which is dose independent), pre-contrast myocardial T1 and blood normalized myocardial T1 values was also performed to validate the correction. There were significant differences in T1(myo,c) (post plasma volume correction) and ECV between current and former smokers (p value 0.017 and 0.01, respectively) but not T1(myo,c) prior to correction (p = 0.12). Prior to dose adjustment for plasma volume, p value was <0.001 for T1(myo,c) between MetS and non-MetS groups and was 0.13 between subjects with and without glucose intolerance; after adjustment for PV, p value was 0.63 and 0.99. Corresponding ECV p values were 0.44 and 0.99, respectively. Overall, ECV results showed the best agreement with PV corrected T1(myo,c) (mean absolute difference in p values = 0.073) and pre-contrast myocardial T1 in comparison with other measures (T1(myo,c( prior to correction, blood/plasma T1 value normalized myocardium). Weight-based contrast dosing administered in mmol/kg results in a bias in T1 values which can lead to erroneous conclusions. After adjustment for lean muscle mass based on plasma volume, results from T1(myo,c) were in line with ECV derived results. Furthermore, the use of a modified equivalent dose adjusted for BMI, age, sex and hematocrit can be adopted for quantitative imaging.


Exchangeable and secondary mineral reactive pools of aluminium in coastal lowland acid sulfate soils.
The use of coastal floodplain sulfidic sediments for agricultural activities has resulted in the environmental degradation of many areas worldwide. The generation of acidity and transport of aluminium (Al) and other metals to adjacent aquatic systems are the main causes of adverse effects. Here, a five-step sequential extraction procedure (SEP) was applied to 30 coastal lowland acid sulfate soils (CLASS) from north-eastern New South Wales, Australia. This enabled quantification of the proportion of aluminium present in 'water-soluble', 'exchangeable', 'organically-complexed', 'reducible iron(III) (oxyhydr)oxide/hydroxysulfate-incorporated' and 'amorphous Al mineral' fractions. The first three extractions represented an average of 5% of 'aqua regia' extractable Al and their cumulative concentrations were extremely high, reaching up to 4000 mg·kg(-1). Comparison of Al concentrations in the final two extractions indicated that 'amorphous Al minerals' are quantitatively a much more important sink for the removal of aqueous Al derived from the acidic weathering of these soils than reducible Fe(III) minerals. Correlations were observed between soil pH, dissolved and total organic carbon (DOC and TOC) and Al concentrations in organic carbon-rich CLASS soil horizons. These results suggest that complexation of Al by dissolved organic matter significantly increases soluble Al concentrations at pH values >5.0. As such, present land management practices would benefit with redefinition of an 'optimal' soil from pH ≥5.5 to ~4.8 for the preservation of aquatic environments adjacent to organic-rich CLASS where Al is the sole or principle inorganic contaminant of concern. Furthermore, it was observed that currently-accepted standard procedures (i.e. 1 M KCl extraction) to measure exchangeable Al concentrations in these types of soils severely underestimate exchangeable Al and a more accurate representation may be obtained through the use of 0.2 M CuCl2.


[Analysis of hypotheses and simulation of selection for a suppressor affecting the manifestations of the fused gene in mice].
The t12 haplotype decreases sharply manifestation of fused gene in mice. The selection for increasing the penetrance of fused gene was made in Fu/t12 stock. The different computer models of selection process were compared. The hypothesis giving the best coincidence with experimental data supposes the presence of a semidominant gene suppressing the effect of t12 on Fu gene in chromosome 8.


Parenting Self-Efficacy and Psychological Distress in Parents of Children with an Autism Spectrum Disorder.
Research suggests that challenges associated with raising a child with an Autism Spectrum Disorder (ASD) can increase parents' risk for diminished parenting self-efficacy (PSE) and psychological wellbeing. The present study aimed to explore interrelationships between noteworthy predictors of PSE and parental psychological distress, including parental mastery beliefs and the co-parenting relationship amongst 122 Australian parents of children with autism. Results indicated that greater mastery beliefs and more favourable co-parenting relationships predicted greater PSE, and higher PSE predicted less psychological distress. PSE significantly mediated relationships between mastery beliefs and psychological distress, and between the co-parenting relationship and psychological distress. Findings have implications that can aid professionals to more effectively support parents raising children on the autism spectrum.


Neural Representation in Visual Word Form Area during Word Reading.
The visual word form area (VWFA) has been consistently identified as a crucial structure in visual word processing. Nevertheless, it is controversial whether the VWFA represents external visual information (e.g., case information) of visual words. To address that question, we functionally localized VWFA at the group level (gVWFA) and at the individual level (iVWFA), and used multivariate pattern analysis (MVPA) to explore the information representation in the VWFA during an implicit reading task (i.e., a passive viewing task). Univariate activation analysis revealed that participants showed stronger activations for uppercase English words compared to lowercase ones in the VWFA. MVPA further revealed that the classifier trained based on lowercase words versus letter strings significantly distinguished uppercase words versus letter strings in the iVWFA, while that trained based on lowercase words versus uppercase words distinguished lowercase letter strings versus uppercase letter strings neither in the gVWFA nor in the iVWFA. These results suggest that the VWFA does not represent case information, but represents case-independent linguistic information. Our findings elaborate the function in the VWFA and support the VWFA hypothesis.


Lentiviral delivered aflibercept OXB-203 for treatment of neovascular AMD.
Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness in the aging population, with vascular endothelial growth factor (VEGF) playing a key role. Treatment with recombinant anti-VEGFs is the current standard of care; however, it is only effective for 1-2 months at a time and requires re-administration. Gene therapy could pave the way for stable, long-term expression of therapeutic anti-VEGF with a single dose, reducing the frequency of treatment and potentially improving clinical outcomes. As such, we have developed OXB-203, a lentiviral-based gene therapy encoding the anti-VEGF protein aflibercept. Aflibercept derived from OXB-203 exhibited comparable in vitro binding characteristics to VEGF as recombinant aflibercept. Furthermore, its biological potency was demonstrated by the equivalent inhibition of VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation and tubule formation as recombinant aflibercept. In a rat choroidal neovascularization (CNV) model of nAMD, a single subretinal administration of OXB-203 reduced laser-induced CNV lesion areas analogous to an intravitreal bolus of recombinant aflibercept. Finally, in a head-to-head comparative study, aflibercept derived from OXB-203 was shown to be expressed at significantly higher levels in ocular tissues than from an AAV8-aflibercept vector following a single subretinal delivery to rats. These findings support the therapeutic potential of OXB-203 for the management of nAMD.


Evaluation of Kenya's readiness to transition from sentinel surveillance to routine HIV testing for antenatal clinic-based HIV surveillance.
Sentinel surveillance for HIV among women attending antenatal clinics using unlinked anonymous testing is a cornerstone of HIV surveillance in sub-Saharan Africa. Increased use of routine antenatal HIV testing allows consideration of using these programmatic data rather than sentinel surveillance data for HIV surveillance. To gauge Kenya's readiness to discontinue sentinel surveillance, we evaluated whether recommended World Health Organization standards were fulfilled by conducting data and administrative reviews of antenatal clinics that offered both routine testing and sentinel surveillance in 2010. The proportion of tests that were HIV-positive among women aged 15-49 years was 6.2% (95% confidence interval [CI] 4.6-7.7%] in sentinel surveillance and 6.5% (95% CI 5.1-8.0%) in routine testing. The agreement of HIV test results between sentinel surveillance and routine testing was 98.0%, but 24.1% of specimens that tested positive in sentinel surveillance were recorded as negative in routine testing. Data completeness was moderate, with HIV test results recorded for 87.8% of women who received routine testing. Additional preparation is required before routine antenatal HIV testing data can supplant sentinel surveillance in Kenya. As the quality of program data has markedly improved since 2010 a repeat evaluation of the use of routine antenatal HIV testing data in lieu of ANC sentinel surveillance is recommended.


Artificial multimodal receptors based on ion relaxation dynamics.
Human skin has different types of tactile receptors that can distinguish various mechanical stimuli from temperature. We present a deformable artificial multimodal ionic receptor that can differentiate thermal and mechanical information without signal interference. Two variables are derived from the analysis of the ion relaxation dynamics: the charge relaxation time as a strain-insensitive intrinsic variable to measure absolute temperature and the normalized capacitance as a temperature-insensitive extrinsic variable to measure strain. The artificial receptor with a simple electrode-electrolyte-electrode structure simultaneously detects temperature and strain by measuring the variables at only two measurement frequencies. The human skin-like multimodal receptor array, called multimodal ion-electronic skin (IEM-skin), provides real-time force directions and strain profiles in various tactile motions (shear, pinch, spread, torsion, and so on).


Combined anterior and posterior ankle impingement syndrome with nonunion of Cedell fracture in a 58-year-old female: a case report.
Combined anterior and posterior ankle impingement has seldom been reported. Cedell fracture, fracture of posteromedial tubercle of talus, is an uncommon and easily missed injury which may elicit posteromedial ankle impingement. The injury mechanisms and management strategies of these two lesions have been reported individually. But the concurrent lesion of both of them has not been reported. We reported a 58-year-old female with combined anterior and posterior ankle impingement syndrome with nonunion of Cedell fracture in whom open osteophytes debridement, fracture internal fixation and posterior talotibial ligament reconstruction were performed. The AOFAS hindfoot score was 90 at 1 year follow-up. To our knowledge, this was the first reported case with anterior, posterior and posteromedial impingement which was treated operatively with an excellent short-term outcome. To fully recognize this occult lesion and avoid missing is imperative for reducing the morbidities. We suggest CT and MRI as excellent imaging modalities that can help the timely diagnosis and appropriate treatment for this combined impingement with circumferential lesions.


Psychological predictors of poor weight loss following LSG: relevance of general psychopathology and impulsivity.
After bariatric surgery (BS) a significant minority of patients do not reach successful weight loss or tend to regain weight. In recent years, interest for the psychological factors that predict post-surgical weight loss has increased with the objective of developing interventions aimed to ameliorate post-surgical outcomes. In the present study, predictive models of successful or poor weight loss 12 months after BS were investigated considering pre-surgery level of psychopathological symptoms, dysfunctional eating behaviors and trait impulsivity at baseline (pre-surgery). Sixty-nine patients with morbid obesity canditates for laparoscopic sleeve gastrectomy were assessed regarding metabolic and psychological dimensions. Successful post-surgery weight loss was defined as losing at least 50% of excess body weight (%EWL). Logistic models adjusted for patient sex, age and presence of metabolic diseases showed that the baseline presence of intense psychopathological symptoms and low attentional impulsivity predict poor %EWL (< 50%), as assessed 12-month post-surgery. The present findings suggest that intensity of general psychopathology and impulsivity, among other psychological factors, might affect post-surgery %EWL. Conducting adequate psychological assessment at baseline of patients candidates for BS seems to be crucial to orient specific therapeutic interventions. Level III, case-control analytic study.


Comparative structural elucidation of the K18, K22, and K100 antigens of Escherichia coli as related ribosyl-ribitol phosphates.
The structures of the capsular K18, K22, and K100 antigens of E. coli O23:K18:H15, O23:K22:H15, and O75:K100:H5, respectively, were elucidated by determination of composition, 1H-, 13C-, and 31P-n.m.r. spectroscopy, periodate oxidation, alkaline hydrolysis followed by incubation with alkaline phosphatase, and methylation analysis of the polymers and their neutral fragmentation products. The polymers are poly(ribosyl-ribitol phosphates) related to the capsular antigen of H. influenzae (Hib). The K22 antigen has the repeating unit -P-2)-beta-Rib-(1----2)-RibOH-(5-, and the K18 antigen has the same polymer chain with partial 3-O-acetylation of the ribose moiety. The K100 antigen consists of repeating units of -P-3)-beta-Rib-(1----2)-RibOH-(5- and seems to have a secondary structure different from that of the other antigens. Together with the Hib capsular antigens, the structure of which was reported as -P-3)-beta-Rib-(1----1)-RibOH-(5-, these capsular antigens represent a structurally related group of capsular polymers.


Interface Engineering to Boost Thermal Safety of Microsized Silicon Anodes in Lithium-Ion Batteries.
Battery safety is vital to the application of lithium-ion batteries (LIBs), especially for high energy density cells applied in electric vehicles. As an anode material with high theoretical capacity and natural abundance, Si has received extensive attention for LIBs. However, it suffers from severe electrode pulverization during cycling due to large volume changes and an unstable solid electrolyte interphase (SEI), resulting in accelerated capacity fading and even safety hazards. Therefore, safe and long-term cycling of Si-based anodes, especially under high-temperature cycling, is highly challenging for state-of-the-art high-energy LIBs. The thermal behavior of SEI is crucial for a high safety battery as the decomposition of SEI is the first step in thermal runaway. Here, highly reversible and thermotolerant microsized Si anodes for safe LIBs are demonstrated. Comprehensive electrochemical/mechanical/thermochemical behaviors of the SEI are systematically investigated. The rational design of robust SEI endows the Si-based cells with long-term durability at elevated temperatures and superior thermal safety. This work paves the way for designing industrial-scale, low-cost, microsized Si anodes with applications in next-generation LIBs with high energy densities and high safety.


Reducing the motor response in haptic parallel matching eliminates the typically observed gender difference.
When making two bars haptically parallel to each other, large deviations have been observed, most likely caused by the bias of a hand-centered egocentric reference frame. A consistent finding is that women show significantly larger deviations than men when performing this task. It has been suggested that this difference might be due to the fact that women are more egocentrically oriented than men or are less efficient in overcoming the egocentric bias of the hand. If this is indeed the case, reducing the bias of the egocentric reference frame should eliminate the above-mentioned gender difference. This was investigated in the current study. Sixty participants (30 men, 30 women) were instructed to haptically match (task HP) the orientation of a test bar with the dominant hand to the orientation of a reference bar that was perceived with the non-dominant hand. In a haptic visual task (task HV), in which only the reference bar and exploring hand were out of view, no motor response was required, but participants had to "match" the perceived orientation by verbally naming the parallel orientation that was read out on a test protractor. Both females and males performed better in the HV task than in the HP task. Significant gender effects were only found in the haptic parallelity task (HP), corroborating the idea that women perform at the same level as men when the egocentric bias of the hand is reduced.


A novel control mechanism based on GDNF modulation of somatostatin release from sensory neurones.
Small-diameter sensory neurones found in the rat dorsal root ganglia (DRG) include cells sensitive to glial cell line-derived neurotrophic factor (GDNF), which express the inhibitory peptide somatostatin (SOM). Here we addressed the functional relationship between GDNF and sensory neurone-derived SOM. Topical application of GDNF through the rat isolated dorsal horn of the spinal cord promoted activity-induced release of SOM from central terminals of sensory neurones. Once released by sensory neurones, SOM is known to act, at least in part, by opposing the action of Substance P (SP) in neurogenic inflammation. Therefore, we evaluated GDNF ability to modulate two well-documented effects of peripherally and centrally administered SP. Local application of GDNF in the mouse air pouch reduced SP-induced leukocyte migration. This effect of GDNF was mimicked by the SOM analog octreotide (OCT) and required intact SOM neuronal pools. Intrathecal injection of GDNF activated rat lumbar dorsal horn neurones and inhibited intrathecal SP-induced thermal hypersensitivity. This effect of GDNF was reversed by the SOM antagonist c-SOM and mimicked by OCT. In conclusion we propose GDNF regulation of neuronal SOM release as a novel mechanism that, if explored, may lead to new therapeutic strategies based on local release of somatostatin.


Publication times, impact factors, and advance online publication in ophthalmology journals.
Publication speed of peer-reviewed journals may play a major role in early dissemination of knowledge and may raise the citation index. In this study, we evaluated the publication speed of ophthalmology journals. Observational study. Observational study of bibliometric data in published ophthalmology journals. A list of ophthalmic journals featured in the 2010 Journal Citation Report was obtained on September 1, 2011. A total of 12 articles were chosen randomly from each of these journals published between January and December 2010. Median publication time and interquartile range (IQR) were obtained from the full texts of the published articles. Time lag between submission and revision, acceptance, and publication of the manuscripts was calculated. Correlation between publication time lag and journal impact factor as well as advance online publication was analyzed. A total of 51 ophthalmic journals were included. There was no statistically significant difference in the impact factors of journals based on their reporting of submission, revision, or acceptance times of the manuscripts (both P>0.05, Wilcoxon test). The median peer review and publication time of all ophthalmology journals was 133 days (IQR, 100.5-171.5) and 100 days (IQR, 62.9-166.3), respectively. There was no correlation between the journal impact factors and publication time lag (Spearman correlation). Approximately half of the ophthalmology journals (n = 26; 50.98%) published online in advance. Journals with advance online publication had higher impact factors compared with those without this feature (median, 1.692 [IQR, 1.05-2.80] vs. 1.02 [0.39-1.53]; P = 0.015, Mann-Whitney U test). For journals with advance online publication, the median time from acceptance to advance online publication (74.3 days [IQR, 48.3-115 days]) was significantly shorter than the median time between acceptance and print publication (170.75 days [IQR, 101.4-217 days]; P<0.001, Wilcoxon test). Publication time lag in ophthalmology journals was not correlated with journal impact factors. Advance online publication facility was provided by only half of the ophthalmology journals published in 2010. Journals with advance online publication had a higher impact factor compared with those without this feature. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Severe Falciparum and Vivax Malaria on the Thailand-Myanmar Border: A Review of 1503 Cases.
The northwestern border of Thailand is an area of low seasonal malaria transmission. Until recent successful malaria elimination activities, malaria was a major cause of disease and death. Historically the incidences of symptomatic Plasmodium falciparum and Plasmodium vivax malaria were approximately similar. All malaria cases managed in the Shoklo Malaria Research Unit along the Thailand-Myanmar border between 2000 and 2016 were reviewed. There were 80 841 consultations for symptomatic P. vivax and 94 467 for symptomatic P. falciparum malaria. Overall, 4844 (5.1%) patients with P. falciparum malaria were admitted to field hospitals, of whom 66 died, compared with 278 (0.34%) with P. vivax malaria, of whom 4 died (3 had diagnoses of sepsis, so the contribution of malaria to their fatal outcomes is uncertain). Applying the 2015 World Health Organization severe malaria criteria, 68 of 80 841 P. vivax admissions (0.08%) and 1482 of 94 467 P. falciparum admissions (1.6%) were classified as severe. Overall, patients with P. falciparum malaria were 15 (95% confidence interval, 13.2-16.8) times more likely than those with P. vivax malaria to require hospital admission, 19 (14.6-23.8) times more likely to develop severe malaria, and ≥14 (5.1-38.7) times more likely to die. In this area, both P. falciparum and P. vivax infections were important causes of hospitalization, but life-threatening P. vivax illness was rare.


A prospective randomized clinical trial to investigate the effect of silicone gel sheeting (Cica-Care) on post-traumatic hypertrophic scar among the Chinese population.
This study aimed to determine the efficacy of silicone gel (Cica-Care) on severe post-traumatic hypertophic scars among the Chinese population. A randomized clinical trial (RCT) was conducted on 45 Chinese patients with post-traumatic hypertrophic scars. Twenty-two subjects were placed in the experimental group with silicone gel sheeting (SGS) applied 24h per day for 6 months while all subjects were taught to massage the scar daily for 15 min serving as the control intervention. Scar assessments were conducted regularly to measure the changes in thickness, pigmentation, vascularity, pliability, itchiness and pain. Two-way repeated ANOVA showed a significant difference between MT group and SGS group on scar thickness. The post hoc comparison analysis showed that the difference was significant at the post-2-month (p=0.008) and post-6-month (p<0.001) intervention. The SGS group also showed changes in pigmentation which resembled normal skin but no statistical significance was found. Pain, itchiness and pliability were also improved after intervention. This study indicated that silicone gel sheeting (Cica-Care) was effective to reduce thickness, pain, itchiness and pliability of the severe hypertrophic scar among the Chinese population. The moisturization effect of the tough and hard scar might contribute to the reduction of the skin thickness after 6 month's intervention.


Preoperative factors that predict fair outcomes following surgery in patients with proximal cervical spondylotic amyotrophy. A retrospective study.
Observational cohort study OBJECTIVES: To investigate preoperative factors that predict fair outcomes following surgery in patients with proximal cervical spondylotic amyotrophy (CSA) using electrophysiological and neurological findings. Yamaguchi University METHODS: 54 patients with proximal CSA who underwent surgical treatment of the cervical spine were enrolled. Erb-point stimulated compound muscle action potentials (CMAP) were recorded from the deltoid and biceps brachii muscles. We computed the ratio of affected to normal side CMAP amplitudes in two muscles (deltoid and biceps brachii) and regarded the mean ratio (CMAP-R) as representing the severity of neural involvement. Pre- and postoperative strengths of the most atrophic muscles were evaluated using manual muscle testing. Improvements in strength were classified as excellent (5 grades recovered), good (more than one grade recovered), fair (no improvement), or poor (worsened). Surgical outcomes were excellent in 26 patients, good in five, fair in 16, poor in seven. Patients with fair outcomes had lower CMAP-R than those patients with excellent and good outcomes [P = 0.0099, odds ratio = 0.89 (95% confidence interval, 0.81-0.97; for a change of 10%)]. Eight patients (15%) had a C5 palsy. CMAP-R could be used as a reliable predictive factor related to a fair surgical outcome. We must pay attention to the incidence of C5 palsy after surgery.


Enhancement of generation of monocyte tissue thromboplastin by bacterial phagocytosis: possible pathway for fibrin formation on infected vegetations in bacterial endocarditis.
The deposition of fibrin on infected vegetations and the presence of mononuclear phagocytes that have phagocytized bacteria are remarkabe features in experimental bacterial endocarditis. In a study in vitro, we show that phagocytosis of bacteria by human monocytes enhances thromboplastin generation by these cells. Maximal enhancement of the generation of thromboplastin by monocytes was about six times compared with that in the control experiment without bacteria, and it was obtained by preincubation of the monocytes with 5 to 10 bacteria per monocyte. No quantitative difference was observed between Staphylococcus epidermidis and Streptococcus sanguis as to the enhancement of the monocyte thromboplastin generation. An enhancement of the procoagulant activity generation was also observed after addition of bacteria to human or rabbit whole blood. Probably, this generation was also due to synthesis of thromboplastin by monocytes. It is conceivable that fibrin deposition on infected vegetations during bacterial endocarditis is mediated by thromboplastin synthesis by monocytes.


Bio-bleaching of Remazol brilliant blue-19 by Stereum ostrea.
Efficiency of white-rot fungi-Stereum ostrea (S. ostrea) as a test culture and Phanerochaete chrysosporium (P. chrysosporium) as a reference culture in colour removal from a textile dye, Remazol brilliant blue-19 (RBB-19) in medium was compared in this study. S. ostrea was more efficient than P. chrysosporium in decoloration process. Different parameters pH, temperature, sources of carbon and nitrogen, stationary and shaking conditions were optimized for bleaching of dye by the fungal cultures. Optimal growth conditions for decoloration of dye by both cultures were pH 5.0, temperature 35 °C, glucose and fructose as best carbon source at 1 % level, peptone and urea as best nitrogen source and shaking conditions (150 rpm). Culture broth free of colour (99 % of decoloration) was achieved with S. ostrea as against 70 % decoloration by P. chrysosporium on 6th day of incubation. Adsorption of dye to fungal biomass as reflected by colour coating on biomass and participation of lignolytic enzymes in colour removal appeared to be mechanisms involved in decoloration process. The ability of both fungal cultures in removal of colour in effluents with dyes collected from silk saree-weaving cottage unit was tested. S. ostrea was also found to be more effective in colour removal from effluent. S. ostrea appears to be a promising culture for application of bioremediation in decoloration of dyes.


Ureteroscopic results and complications: experience with 130 cases.
Since its introduction for general use, the role of rigid ureteroscopy in the diagnosis and therapy of urological disease has been in evolution. We evaluated retrospectively the experience at our institution with rigid ureteroscopy from January 1983 to July 1986 in an attempt to identify clinical situations or techniques that tended to increase the incidence of either success or complications. We determined that ureteroscopic complications were rare in procedures performed for diagnosis compared to those performed for calculi (2 of 33 or 6 per cent versus 27 of 99 or 27 per cent, p less than 0.025). The likelihood of failure or complication was greater for stones above than for those below the pelvic brim (15 of 25 or 60 per cent versus 26 of 75 or 35 per cent, p less than 0.05). Major complications were more common early in our experience (9 of 63 or 14 per cent versus 2 of 69 or 3 per cent for the combined years 1983 and 1984 compared to 1985 and 1986, p less than 0.05). Our success rates in the treatment of calculous disease were similar to those reported previously, and they were somewhat better for stones located below (62 of 75 or 83 per cent) than for those above (17 of 25 or 68 per cent) the pelvic brim. Based on our findings we conclude that carefully performed diagnostic ureteroscopy has little potential for major complications, ureteroscopy for stones above the pelvic brim should be avoided when possible, and an increased rate of complications and failures is expected early in any series owing at least partly to the learning curve effect.


Connecting Socially Isolated Older Rural Adults with Older Volunteers through Expressive Arts.
Employing a participatory arts-based research approach, we examined an innovative program from rural Ontario, Canada, designed to address social isolation among older people. Older socially isolated adults were matched to trained volunteers, where in dyads, the eight pairs created expressive art in their home setting over the course of 10 home visits. With thematic and narrative inquiry, we analysed the experiences and perceptions of the program leader, older participants, and older volunteers via their artistic creations, weekly logs, evaluations, and field notes. The findings reveal a successful intervention that positively influenced the well-being of older adult participants and older volunteers, especially in regards to relationships, personal development, and creating meaning as well as extending the intervention's impact beyond the program's duration. We also discuss opportunities for similar programs to inform policy and enable positive community-based health and social service responses to rural social isolation.


Structure, dissociation, and proteolysis of mammalian steroid receptors. Multiplicity of glucocorticoid receptor forms and proteolytic enzymes in rat liver and kidney cytosols.
The forms of steroid receptors detected in mammalian tissue cytosols vary from a globular fragment, the mero-receptor, with a molecular weight (Mr) of approximately 23,000 to highly asymmetric molybdate-stabilized complexes (Mr approximately 330,000). Our objectives were to investigate the relationships among various receptor forms and mechanisms of stabilization by Na2MoO4, to characterize endogenous proteolytic enzymes, and to evaluate the effects of freezing the tissues on receptor structure and protease activities in the resultant cytosols. Glucocorticoid receptors and proteases were analyzed in cytosols from fresh and frozen rat liver and kidney. Enzymes were assayed fluorometrically at approximately 24 degrees C, with peptidyl tyrosine, lysine, and phenylalanine derivatives of 7-amino-4-methylcoumarin. Rates of cleavage of the tyrosine-containing substrate by crude and partially purified liver cytosol enzymes were markedly suppressed by Na2MoO4. While receptor cleavage by these enzymes has not been demonstrated, these results illustrate the direct inhibition of proteolysis by molybdate. Rates of cleavage of the lysine-containing substrate were 7- to 40-fold higher in cytosols from frozen liver and fresh or frozen kidney, in which the Stokes radius (Rs) of the largest receptor form was 70-74 A, than in fresh liver cytosol, in which Rs was 84 +/- 2 A (n = 20). Filtration of the 84 A complex (Mr approximately 330,000) in hypertonic buffer without Na2MoO4 revealed a 7:3 mixture of forms with Rs of 50-60 A (Mr approximately 90,000) and Rs of 30-40 A (Mr approximately 50,000). The latter are derived from the 50-60 A forms by proteolysis and/or dissociation. We conclude that the 84 A (untransformed) receptor is an oligomer, probably a tetramer, containing the 50-60 A subunits and that purification of the intact structure will require removal or inactivation of contaminating proteases.


Interfacial reactions of osteoblasts to dental and implant materials.
Scanning electron microscopy was used to study the response of osteoblasts to various surfaces including ceramics and glasses as well as steel and titanium. Hydroxylapatite, tricalcium phosphate, bioglass, steel, and titanium supported cell adhesion. However, the toxic effects of the In-Ceram (Vita, Bad Säckingen, Germany), and feldspar ceramic and glaze were severe enough to cause verrucous necrosis that was identifiable after 2 days of culture. After 10 days in culture only the peripheral portions of these specimens were still occupied by cells; the cells in the central portion of the circular specimens had succumbed to necrosis. It was concluded that scanning electron microscopy is useful in identifying the response of cells to materials. Pathologic changes are not recognizable if they are limited to the internal structure of the cell, but readily discernible when they impinge on the morphologic integrity of the cell surface.


An Immunohistochemical Study of HIF-1 Alpha in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma.
To evaluate and compare the expression of HIF-1 Alpha (HIF-1α) in oral epithelial dysplasia (OED) and various grades of Oral squamous cell carcinoma (OSCC). 30 cases each of OEDand OSCC were stained with HIF-1α antibody. Quantification of HIF-1α positive cellswas carried out and the data was statistically analysed. The mean % HIF-1α labeling index (HIF-1α LI) increased significantly from mild OED (32.11%), moderate OED (55.07%), to severe OED (64.58%). There was a statistically significant increase in the expression of HIF-1α as grades of OED increased. The mean HIF-1α LI % in well differentiated OSCC was 46.3%, Moderately differentiated OSCC-76.31% and Poorly differentiated OSCC-89.9%. The mean HIF-1α LI was found to increase with increasing grades of OSCC which was statistically significant (P < 0.05). Further a comparison of mean HIF-1α LI in OED with different histologic grades of OSCC by Independent samples t test was performed. We found statistically significant difference between OED and moderately differentiated OSCC and OED and poorly differentiated OSCC (P = 0.000). Progressive increase in expression of HIF-1α was noted from OED to OSCC. It can be postulated that epithelial dysplastic lesions with increased HIF-1α expression are at greater risk of malignant transformation, suggesting that the expression of HIF-1α is an early event in oral carcinogenesis.


Ablative fractional laser treatment for hypertrophic scars: comparison between Er:YAG and CO2 fractional lasers.
Nonablative fractional photothermolysis has been reported to show early promise in the treatment of hypertrophic scars, but there are few reports on ablative fractional photothermolysis for the treatment of hypertrophic scars. To evaluate and compare the efficacy and safety of Er:YAG fractional laser (EYFL) and CO2 fractional laser (CO2FL) for treatment of hypertrophic scars. Thirteen patients with hypertrophic scars were treated with 2,940 nm EYFL, and ten were treated with 10,600 nm CO2FL. An independent physician evaluator assessed the treatment outcomes using Vancouver scar scale (VSS) and 5-point grading scale (grade 0, no improvement; grade 1, 1-25%; grade 2, 26-50%; grade 3, 51-75%; grade 4, 76-100% improvement). Patients are queried about their subjective satisfaction with the treatment outcomes. After the final treatment, average percentage changes of VSS were 28.2% for EYFL and 49.8% for CO2FL. Improvement was evident in terms of pliability, while insignificant in terms of vascularity and pigmentation. Based on physician's global assessment, mean grade of 1.8 for EYFL and 2.7 for CO2FL was achieved. Patient's subjective satisfaction scores paralleled the physician's objective evaluation. CO2FL is a potentially effective and safe modality for the treatment of hypertrophic scars, particularly in terms of pliability.


Patterns of gallium uptake in amebic liver abscesses.
Imaging with Ga-67 and Tc-99m sulfur colloid was performed in ten patients with amebic liver abscesses. The most common imaging pattern appeared to be with the sharp identification of a "rim" sign on delayed Ga-67 imaging, from 48-72 hours.


The dissociation paradigm and its discontents: how can unconscious perception or memory be inferred?
Erdelyi does us all a great service by his customarily incisive discussion of the various ways in which our field tends to neglect, confuse, and misunderstand numerous critical issues in attempting to differentiate conscious from unconscious perception and memory. Although no single commentary could hope to comprehensively assess these issues, I will address Erdelyi's three main points: (1) How (and if) the dissociation paradigm can be used to validly infer unconscious perception; (2) The implications of below-chance effects; and (3) The role of time. I suggest that (a) significant progress on construct validity issues is possible; (b) below-chance effects are part of a more general bidirectional phenomenon, very likely unconscious, and do not threaten absolute subliminality; and (c) practice/learning effects pose potential difficulties for time-based dissociation paradigms.


[Infectious disease surveillance based on the Protection against Infection Act in the German public health sector].
By the Protection against Infection Act new instruments were established for infectious disease surveillance in Germany. The main innovations were a shift of responsibility for notifications from clinicians to laboratories, the validation of cases by means of case definitions in local public health departments, and the electronic transmission of single case data via state health departments to the Robert Koch Institute. Four years after the Protection against Infection Act was enacted, its implementation was successful from the perspective of state and national health authorities. This was proven by the detection and successful investigation of several diffuse outbreaks. However, further improvements seem necessary and the following points should be considered in a revision of the act: reduction of time limits for data transmission, unambiguous regulation of responsibilities and for data exchange in non-localized outbreaks as well as for international exchange of case data, and introduction of an obligation for clinicians to supply local public health departments with complementary information regarding laboratory reports on demand. The public health sector can contribute to a further improvement of the surveillance system by working to better inform clinicians and laboratories and therewith motivate them to comply with their obligations for notifying diseases and by promoting the scientific evaluation of the system, in particular concerning potential underreporting.


A primary intrapelvic hydatid cyst presenting with foot drop and a gluteal swelling: a case report.
A primary hydatid cyst in the pelvis is rare, and usually presents with pressure symptoms affecting the adjacent abdominal organs. We describe such a cyst which protruded through the sciatic notch and presented as a gluteal swelling with a foot drop due to compression of the lumbosacral nerve roots. Surgical excision and postoperative treatment with albendazole for six weeks were effective in controlling the disease and preventing recurrence.


Dicer and microRNA expression in multiple sclerosis and response to interferon therapy.
Dysregulation of microRNA expression has been shown in multiple sclerosis (MS); however, the mechanisms underlying these changes, their response to therapy and the impact of microRNA changes in MS are not completely understood. Dicer mediates the cleavage of precursor microRNAs to mature microRNAs and is dysregulated in multiple pathologies. Having shown that interferons regulate Dicer in vitro, we hypothesized that MS patient IFNβ1a treatment could potentially alter Dicer expression. Dicer mRNA and protein levels, as well as microRNA expression, were determined in MS patient and healthy control PBL. Acute responses to IFNβ1a were assessed in 50 patients. We found that Dicer protein but not mRNA levels decreases in MS patients while both are selectively induced in patients responding well to IFNβ1a. Potential microRNA biomarkers for relapsing remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and IFNβ1a response are described. Contrasts in Dicer and microRNA expression levels between patient populations may offer insight into mechanisms underlying disease courses and responses to IFNβ1a therapy. This work identifies Dicer regulation as both a potential mediator of MS pathology and a therapeutic target.


Encouraging GP alcohol intervention: pilot study of change-orientated reflective listening (CORL).
To test the feasibility of delivery and potential value of a brief motivational enhancement intervention targeting GPs in relation to alcohol as a public health issue, and to compare data obtained with similar attempts to influence GP intervention with drug users. 21 GPs who were not involved in the treatment of drug dependence received a telephone-administered 'change-orientated reflective listening' (CORL) intervention, based on Motivational Interviewing, with an informational adjunct. Assessments were made at baseline and at 2-3 months of activity and willingness to deliver specified alcohol-related interventions, plus overall therapeutic commitment and motivation. Qualitative data was obtained. There was no change over time in the sample as a whole, with very modest evidence of benefit among individual practitioners. Comparisons with cannabis and drug misuse intervention targets suggest that it may be more difficult to alter views on intervening with drinkers. Further attempts are needed to influence practitioner motivation, based on improved understanding of GP views on the delivery of alcohol interventions.


Exploring racial disparities on the association between allostatic load and cancer mortality: A retrospective cohort analysis of NHANES, 1988 through 2019.
Several studies suggest that chronic stress may be associated with increased risk of cancer mortality. Our study sought to determine the association between allostatic load (AL), a measure of cumulative stress, and risk of cancer death; and whether these associations varied by race/ethnicity. We performed retrospective analysis using National Health and Nutrition Examination Survey (NHANES) years 1988 through 2010 linked with the National Death Index through December 31, 2019. We fit Fine & Gray Cox proportional hazards models to estimate sub-distribution hazard ratios (SHRs) of cancer death between high and low AL status (models adjusted for age, sociodemographics, and comorbidities). In fully adjusted models, high AL was associated with a 14% increased risk of cancer death (adjusted (SHR): 1.14, 95% CI: 1.04-1.26) among all participants and a 18% increased risk of cancer death (SHR:1.18, 95% CI: 1.03-1.34) among Non-Hispanic White (NH-White) adults. When further stratified by age (participants aged <40 years), high AL was associated with a 80% increased risk (SHR: 1.80, 95% CI: 1.35-2.41) among all participants; a 95% increased risk (SHR: 1.95, 95% CI: 1.22-3.12) among NH-White adults; a 2-fold (SHR: 2.06, 95% CI: 1.27-3.34) increased risk among Non-Hispanic Black (NH-Black) adults; and a 36% increased risk among Hispanic adults (SHR: 1.36, 95% CI: 0.70-2.62). Overall, the risk of cancer death was associated with high AL; however, when stratified among NH-Black and Hispanic adults this association was slightly attenuated. High AL is associated with increased risk of overall cancer death, and future studies should delineate the association between AL and cancer-specific mortality to better understand the causal mechanisms between cumulative stress and cancer.


The shifting research landscape for PAH bioremediation in water environment: a bibliometric analysis on three decades of development.
Polycyclic aromatic hydrocarbons (PAHs) with their carcinogenic, teratogenic, and mutagenic effects can cause great damage to the ecosystem and public health when present in water. With bioremediation, PAH contamination in water environment can be greatly reduced in an eco-friendly manner. It has thus become the research focus for many environmental scientists. In this study, a bibliometric analysis on three-decade (1990-2022) development of PAH bioremediation in water environment was conducted from temporal and spatial dimensions using CiteSpace. A total of 2480 publications, obtained from Web of Science core collection database, were used to explore the basic characteristics, hotspots, and prospects of the research area. The results showed that (1) bioremediation/biodegradation of PAHs in water environment has been getting researchers' attention since 1990, and is gaining even more traction as time goes on. (2) In terms of countries, China and the USA were the major contributors in this research area, while at the institutional level, the Chinese Academy of Sciences has produced the most research results. However, international cooperation across regions was lacking in the field. (3) Environment Science and Technology, Chemosphere, Applied and Environment Microbiology, Journal of Hazardous Materials, and Environment Pollution were the 5 most cited journals in this field. (4) There were three major stages the field has gone through, each with distinct research hotspots, including initial stage (1990-1994), mechanism investigation (1995-2000), and application exploration (2001-2010; 2011-2022). Finally, research perspectives were proposed, covering three directions, namely, bioavailability, immobilization, and viable but nonculturable (VBNC) bacteria.


Thin needle biopsy as a routine method for rapid diagnosis of neoplasms.
The present communication demonstrates the possibility of applying the "thin needle biopsy" as a routine method for rapid cytologic diagnosis of neoplasms. Systematically used in the examination of pulmonary, mammary, and thyroid tumors, the "thin needle biopsy" offers the following advantages: 1) decreased occurrence of so-called "false negative diagnoses"; 2) psychological relief for the patient; 3) decreased cost.


Inventory management performance for laboratory commodities in public hospitals of Jimma zone, Southwest Ethiopia.
Maintaining an efficient and effective inventory management system ensures a reliable supply of laboratory commodities. The aim of this study was, therefore, to assess the performance of inventory management for laboratory commodities in public hospitals in the Jimma zone. A facility-based cross-sectional descriptive study, accompanied by a qualitative method, was conducted in seven public hospitals between April 30 and May 29, 2019. We collected data through document reviews (225 bin-cards), physical observation, self-administered questionnaires, and in-depth interviews. The quantitative data were analyzed using Excel spreadsheets and SPSS version 24. Fifteen key informants of different backgrounds took part in the qualitative study. The data were then analyzed using thematic analysis techniques. All the public hospitals in the zone were included in the study, making a response rate of 100%. Of the total estimated bin-cards, 225 (69.9%) of them held along with the items, and only 30.4% of them filled accurately. In four of the hospitals, pharmacists determined how much to order. Five of the hospitals used average monthly consumption data to calculate purchase quantity. Over the past 6 months, four of the hospitals had placed at least one or two emergency orders. The wastage rate of the commodities in the hospitals was 27.2% and resulted in a loss of about 10,248.5 US dollars. The hospitals had met 70.6% of the criteria for proper storage conditions. Budget constraints, absence of prompt administrative support, lack of staff commitment, and frequent shortages of commodities on the part of suppliers were major bottlenecks of inventory management. The hospitals had weak inventory management practices, showed by inaccurate records, stock-outs (frequent emergency orders), a high wastage rate compared to national baseline statistics, and the storage conditions below the standard.


Seasonal and Spatial Variation of Groundwater Quality Vulnerable Zones of Yellareddygudem Watershed, Nalgonda District, Telangana State, India.
Evaluation of seasonal and spatial variations in vulnerable zones for poor groundwater quality is essential for the protection of human health and to maintain the crop yields. With this objective, groundwater samples were collected seasonally (i.e., pre- and post-monsoon) from the Yellareddygudem watershed of Telangana, India. These samples were analysed for major chemical parameters (pH, TDS, Ca2+, Mg2+, Na+, K+, [Formula: see text], Cl-, [Formula: see text], [Formula: see text], and F-). Geographical information system (GIS) tools were used to delineate the seasonal and spatial variations for vulnerable zones related to the drinking groundwater quality index (DGQI) and irrigation groundwater quality index (IGQI). Geochemical facies and relations, Piper diagrams, and principal component analysis indicated that the weathering, dissolution, leaching, ion exchange, and evaporation were the primary processes controlling the groundwater quality seasonally. Human influences were the secondary factors. The TDS, Na+, K+, Cl-, [Formula: see text], and F- parameters were observed to be within the drinking water quality standard limits in most post-monsoon groundwater samples. However, the DGQI showed an increase in the number of samples with unsuitable quality for drinking in the post-monsoon period compared with the pre-monsoon period. The IGQI demonstrated that the number of samples with unsuitable quality for irrigation increased in the post-monsoon period compared to the pre-monsoon period. The differences in the vulnerable zones between the pre- and post-monsoon periods were due to variations in groundwater recharge, following the topography. Thus, the present study will help decision makers to plan groundwater treatment measures within vulnerable zones.


Recurring acute abdominal pains in an adolescent as the presenting manifestations of hereditary angioneurotic oedema.
An adolescent was hospitalized for recurring abdominal pains, which had previously led to appendicectomy. Laboratory data finally led to the diagnosis of hereditary angioneurotic oedema, after several hypotheses had been raised and ruled out. Angioneurotic oedema is a rare condition, which should be suspected in children with recurring abdominal pains, especially when there is liquid within the peritoneal cavity.


Genetic parameters and genomic breeding values for digital dermatitis in Holstein Friesian dairy cattle: host susceptibility, infectivity and the basic reproduction ratio.
For infectious diseases, the probability that an animal gets infected depends on its own susceptibility, and on the number of infectious herd mates and their infectivity. Together with the duration of the infectious period, susceptibility and infectivity determine the basic reproduction ratio of the disease ([Formula: see text]). [Formula: see text] is the average number of secondary cases caused by a typical infectious individual in an otherwise uninfected population. An infectious disease dies out when [Formula: see text] is lower than 1. Thus, breeding strategies that aim at reducing disease prevalence should focus on reducing [Formula: see text], preferably to a value lower than 1. In animal breeding, however, [Formula: see text] has received little attention. Here, we estimate the additive genetic variance in host susceptibility, host infectivity, and [Formula: see text] for the endemic claw disease digital dermatitis (DD) in Holstein Friesian dairy cattle, and estimate genomic breeding values (GEBV) for these traits. We recorded DD disease status of both hind claws of 1513 cows from 12 Dutch dairy farms, every 2 weeks, 11 times. The genotype data consisted of 75,904 single nucleotide polymorphisms (SNPs) for 1401 of the cows. We modelled the probability that a cow got infected between recordings, and compared four generalized linear mixed models. All models included a genetic effect for susceptibility; Models 2 and 4 also included a genetic effect for infectivity, while Models 1 and 2 included a farm*period interaction. We corrected for variation in exposure to infectious herd mates via an offset. GEBV for [Formula: see text] from the model that included genetic effects for susceptibility only had an accuracy of ~ 0.39 based on cross-validation between farms, which is very high given the limited amount of data and the complexity of the trait. Models with a genetic effect for infectivity showed a larger bias, but also a slightly higher accuracy of GEBV. Additive genetic standard deviation for [Formula: see text] was large, i.e. ~ 1.17, while the mean [Formula: see text] was 2.36. GEBV for [Formula: see text] showed substantial variation. The mean [Formula: see text] was only about one genetic standard deviation greater than 1. These results suggest that lowering DD prevalence by selective breeding is promising.


Constructing HIV-1 integrase tetramer and exploring influences of metal ions on forming integrase-DNA complex.
HIV-1 integrase (IN) is essential for the replication of HIV-1 in human cells. At present, the complete structure of complex IN-DNA has not been resolved. In this paper, a HIV-1 IN tetramer model was built with homology modeling and molecular dynamics simulation approach, in which two Mg2+ ions were reasonably located in each catalytic core domain. Moreover, it was found that the AB and CD chains of HIV-1 IN tetramer were different in the structures and metal ions of HIV-1 IN tetramer might have great influences on DNA locating on IN. These findings may provide a more complete structural basis for guiding drug discovery and revealing integration mechanism.


Complete bilateral internal ophthalmoplegia as sole clinical sign of botulism: confirmation of diagnosis by single fibre electromyography.
A case of complete bilateral internal ophthalmoplegia as the sole clinical sign of botulism is reported. Diagnosis was immediately confirmed by single-fibre electromyography (SFEMG), which revealed abnormally high blocking (14.3%), contrasting with moderately increased jitter (mean consecutive difference in the extensor digitorum communis muscle, 43.9 microseconds). After giving equine botulinum antitoxin and simultaneous forced emptying of the bowels, ocular symptoms completely disappeared within 2 days. Six days, 5 weeks and 6 months after the first SFEMG study, the jitter was still abnormal, even becoming more so with time. Blocking, however, was only rarely observed in the follow-up studies. It is concluded that SFEMG may serve as a useful and sensitive method for the rapid diagnosis of botulinum intoxication, even in cases where no clinical signs of general muscular weakness are apparent.


The impact of posttraumatic stress disorder on impairment in the UK military at the time of the Iraq war.
The aims of this study were to assess: (1) the relationship between PTSD and impairment, (2) whether there is a threshold in the association of PTSD score and impairment, and (3) whether any of the PTSD criteria are more strongly associated with impairment. We studied 10,069 service personnel from a representative sample of the British Armed Forces to assess the effects of the Iraq war. Participants completed the PTSD checklist (PCL), the general health questionnaire-12 (GHQ-12), the alcohol use disorder identification test (AUDIT) and five questions to assess impairment. 78% of those with a PCL-score of 50 or more endorsed at least one impairment item in comparison to 27% of those with a score below 50. The odds ratio (OR) of impairment in the PCL group with a score of 50 or more was 16.7 (95% CI 12.9-21.6). There was an increasing risk of impairment with an increasing category of PCL-score without a noticeable threshold. For each PTSD subscale: intrusiveness, avoidance/numbing and hyper-arousal, divided into four score categories, there was an increased association with impairment, but the association of avoidance/numbing with impairment was the greatest and independent of the other two criteria (OR 7.2 (95% CI 4.8-10.9). Having a good relationship with a partner had minimal effect on the level of association between PTSD and impairment. Functional impairment is a serious problem for those with PTSD. The impairment is not confined to those with the highest PCL-score. Avoidance/numbing is the criterion which makes the greatest independent contribution to impairment.


Development of certified calibrants for the analysis of zearalenone and B-trichothecenes.
Recent intercomparison studies have clearly shown that the use of common calibrants does considerably improve the between laboratory comparability of measurement results. However, there is still a lack of certified calibrants within the field of mycotoxin analysis. Therefore, two EC-funded projects have been carried out with the aim to investigate the feasibility for the production of calibrants with certified concentrations of B-trichothecenes and for the production of a certified calibrant of zearalenone in acetonitrile.


Analysis of the lipid composition of human and boar spermatozoa by MALDI-TOF mass spectrometry, thin layer chromatography and 31P NMR spectroscopy.
Alterations in the phospholipid (PL) composition of spermatozoal membranes occur during the fertilization process. Furthermore, membrane lipid composition is of high interest with respect to cryopreservation. The PL and fatty acid compositions of human and boar spermatozoa are compared by using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) in combination with thin-layer chromatography and 31P NMR spectroscopy. The extreme sensitivity of alkenyl-linked PL against acid treatment was used to estimate the plasmalogen content of spermatozoa. Compared with humans, boar spermatozoa are characterized by a lower variability of their PL and fatty acid composition. Additionally, boar spermatozoa contain much higher moieties of alkyl-linked compounds, e.g. 1-palmityl-2-docosapentaenoyl-sn-glycero-3-phosphocholine and 1-palmityl-2-docosahexaenoyl-sn-glycero-3-phosphocholine as well as the corresponding phosphatidylethanolamine (PE), while human spermatozoa are characterized by high contents of diacyl-PL, e.g. 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine. A considerable plasmalogen moiety, for instance 1-palmitenyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine is a typical feature of both, human and boar spermatozoa. It will be shown that these differences in PL composition can be very rapidly and conveniently assessed by MALDI-TOF MS in combination with TLC and also by 31P NMR.


Reversal of novel oral anticoagulants.
The development of a new generation of non-vitamin K oral anticoagulants represents a potential breakthrough in the management of patients with thrombotic diseases, disorders and conditions. While a large and growing body of evidence from large-scale clinical trials and registries supports a favorable safety profile, having a means to rapidly reverse their anticoagulant effects represents an unmet need among practicing clinicians. Several targeted reversal agents are currently in development and the early results are promising. Idarucizumab is a monoclonal antibody that can immediately and specifically reverse dabigatran. Andexanet alfa is a recombinant modified factor Xa that can bind and reverse oral and parenteral factor Xa inhibitors, including rivaroxaban, apixaban and edoxaban, and low molecular weight heparin. Aripazine is a small molecule that can reverse the action of factor Xa inhibitors and possibly dabigatran as well through non-covalent binding and charge-charge interactions.


The Dionaea muscipula ammonium channel DmAMT1 provides NH₄⁺ uptake associated with Venus flytrap's prey digestion.
Ammonium transporter (AMT/MEP/Rh) superfamily members mediate ammonium uptake and retrieval. This pivotal transport system is conserved among all living organisms. For plants, nitrogen represents a macronutrient available in the soil as ammonium, nitrate, and organic nitrogen compounds. Plants living on extremely nutrient-poor soils have developed a number of adaptation mechanisms, including a carnivorous lifestyle. This study addresses the molecular nature, function, and regulation of prey-derived ammonium uptake in the Venus flytrap, Dionaea muscipula, one of the fastest active carnivores. The Dionaea muscipula ammonium transporter DmAMT1 was localized in gland complexes where its expression was upregulated upon secretion. These clusters of cells decorating the inner trap surface are engaged in (1) secretion of an acidic digestive enzyme cocktail and (2) uptake of prey-derived nutrients. Voltage clamp of Xenopus oocytes expressing DmAMT1 and membrane potential recordings with DmAMT1-expressing Dionaea glands were used to monitor and compare electrophysiological properties of DmAMT1 in vitro and in planta. DmAMT1 exhibited the hallmark biophysical properties of a NH4(+)-selective channel. At depolarized membrane potentials (Vm = 0), the Km (3.2 ± 0.3 mM) indicated a low affinity of DmAMT1 for ammonium that increased systematically with negative going voltages. Upon hyperpolarization to, e.g., -200 mV, a Km of 0.14 ± 0.015 mM documents the voltage-dependent shift of DmAMT1 into a NH4(+) transport system of high affinity. We suggest that regulation of glandular DmAMT1 and membrane potential readjustments of the endocrine cells provide for effective adaptation to varying, prey-derived ammonium sources.


Sonographic biometry of liver and spleen size in childhood.
In 194 healthy children of all ages, sonographic measurements of the liver and spleen were performed on standardized section planes and normal values established. These measurement values showed an approximately linear increase in the course of development and correlated best with the body length. For a rapid orientational evaluation of the liver size, sonographic nomograms of the individual measurements were developed. The spleen size was determined by volume calculation. On the basis of an index of liver size, which was calculated from the individual measurements, a diagram for simultaneous determination of liver and spleen size could be developed. These nomograms permit objective morphometry of size changes in the two organs.


Extraction of information on elder motor ability from clinical and biomechanical data through data mining.
This study aimed at evaluating the additional knowledge provided by a biomechanical test coupled with clinical tests for motor ability assessment. A database including clinical test scores and sit-to-stand test variables obtained from 110 medically stable elderly subjects was submitted to data mining by searching for association rules. The presence of rules revealed some redundancies due to sample homogeneity, as mainly observed in the joint analysis of a questionnaire for daily activities assessment (Nottingham test) and the sit-to-stand, and due to similar evaluated information, as resulted from the joint analysis of a balance and gait scale (Tinetti test) and the sit-to-stand. Conversely, when no association rules were found, the tests carried unrelated information. The associations mined while analysing these clinical tests encouraged the integration of biomechanical tests, increasing significantly its clinical applicability and reducing the information redundancy. The information extracted also allowed to highlight rules typical of elderly persons that may serve as a knowledge-based tool for the detection of possible deviation from normality.


Validity of and recommendations for knee joint acoustic assessments during different movement conditions.
Knee joint sounds contain information on joint health, morphology and loading. These acoustic signals may be elicited by further, as yet unknown factors. By assessing potential elicitors and their relative contributions to the acoustic signal, we investigated the validity of vibroarthrographic assessments during different movement conditions with the aim to derive recommendations for their practical usage. Cross-sectional study. Nineteen healthy participants (24.7 ± 2.8 yrs, 7 females) performed five movements: level walking, descending stairs, standing up, sitting down, and forward lunge. Knee joint sounds were recorded by two microphones (medial tibial plateau, patella). Knee joint kinematics and ground reaction forces were recorded synchronously to calculate knee joint moments (Nm/Kg). The mean amplitude (dB) and the median power frequency (Hz) were determined. A repeated measures mixed model investigated the impact of potential predictors (sagittal, frontal, transverse plane and total knee joint moments, knee angular velocity, age, sex, body mass index (BMI) and Tegner Activity Score (TAS)). Most of the amplitudes variance is explained by between-subject differences (tibia: 66.6%; patella: 75.8%), and of the median power frequencies variance by the movement condition (tibia: 97.6%; patella: 98.9%). The final model revealed several predictor variables for both sensors (tibia: sagittal plane, frontal plane, and total knee joint moments, age, and TAS; patella: sagittal plane knee moments, knee angular velocity, TAS). The standardization of the execution of the activities, a between-group matching of variables and the inclusion of co-variates are recommended to increase the validity of vibroarthrographic measurements during different movement conditions of the knee joint.


Dimethylthiourea reduces ischemic brain edema without affecting cerebral blood flow.
Oxygen free radicals have been implicated as mediators of tissue damage in ischemic brain. We previously demonstrated that the hydroxyl radical scavenger 1,3-dimethyl-2-thiourea (DMTU) reduces infarct size after middle cerebral artery occlusion (MCAO) in rats. The present study was undertaken to determine whether this protection results from a preservation of the CBF. Adult male Sprague-Dawley rats were treated with DMTU (750 mg/kg i.p.) or saline vehicle 1 h before right MCAO. One-half 4, or 24 h after MCAO, animals were killed and samples were taken from the central, intermediate, and outer zones of the MCA distribution of each cortical mantle. Separate groups of animals were used to analyze these samples for water content (wet and dry weight), CBF [( 14C]butanol), or blood-brain barrier permeability [( 3H]alpha-aminoisobutyric acid). CBF was reduced in a graded fashion in the ischemic cortex: 0.169 +/- 0.020, 0.261 +/- 0.017, and 0.435 +/- 0.023 ml/g/min (mean +/- SEM, n = 8) after 4 h in the central, intermediate, and outer zones, respectively. Brain edema was present in a similar pattern, while blood-brain barrier permeability remained normal. Treatment with DMTU significantly reduced brain edema in the central and intermediate zones at both 4 and 24 h. However, CBF in the DMTU-treated animals was identical to that of the vehicle-treated animals. These results suggest that hydroxyl radicals play a role in the development of ischemic brain edema, but the mechanism does not appear to involve a direct effect on CBF.


Vocalisation Repertoire at the End of the First Year of Life: An Exploratory Comparison of Rett Syndrome and Typical Development.
Rett syndrome (RTT) is a rare, late detected developmental disorder associated with severe deficits in the speech-language domain. Despite a few reports about atypicalities in the speech-language development of infants and toddlers with RTT, a detailed analysis of the pre-linguistic vocalisation repertoire of infants with RTT is yet missing. Based on home video recordings, we analysed the vocalisations between 9 and 11 months of age of three female infants with typical RTT and compared them to three age-matched typically developing (TD) female controls. The video material of the infants had a total duration of 424 min with 1655 infant vocalisations. For each month, we (1) calculated the infants' canonical babbling ratios with CBRUTTER, i.e., the ratio of number of utterances containing canonical syllables to total number of utterances, and (2) classified their pre-linguistic vocalisations in three non-canonical and four canonical vocalisation subtypes. All infants achieved the milestone of canonical babbling at 9 months of age according to their canonical babbling ratios, i.e. CBRUTTER ≥ 0.15. We revealed overall lower CBRsUTTER and a lower proportion of canonical pre-linguistic vocalisations consisting of well-formed sounds that could serve as parts of target-language words for the RTT group compared to the TD group. Further studies with more data from individuals with RTT are needed to study the atypicalities in the pre-linguistic vocalisation repertoire which may portend the later deficits in spoken language that are characteristic features of RTT.


The binding of fd gene-5 protein to single-stranded nucleic acid.
The gene-5 protein of the fd filamentous bacterial virus binds to single-stranded DNA over a pH range of 2-10.3. Binding to fd DNA is several hundred-fold stronger than to bacteriophage R17 RNA or to DNA tetranucleotides.


Desferrioxamine therapy in hemodialysis patients with aluminum-associated bone disease.
Aluminum toxicity in dialysis patients is associated with decreased bone turnover and a relative parathyroid hormone (PTH) deficiency. Desferrioxamine (DFO), a chelating agent, has been reported to improve bone histology in aluminum associated, low turnover bone disease in dialysis patients not subjected to parathyroidectomy. Information on the effect of DFO therapy on parathyroid gland function is lacking. In the present study, in addition to changes in bone histology, parathyroid gland function was evaluated in 18 hemodialysis patients with aluminum associated, low turnover bone disease (osteomalacia and aplastic bone disease) before and after one year of DFO treatment (1 to 6 g/week). Parathyroid gland function was assessed by using a calcium free and high calcium (3.5 to 4 mEq/liter) hemodialysis bath.(ABSTRACT TRUNCATED AT 250 WORDS)


Fast ultrasound-assisted synthesis of highly crystalline MIL-88A particles and their application as ethylene adsorbents.
Highly crystalline MIL-88A particles have been successfully synthesized via fast ultrasound-assisted processes. The influence of the sonication generator and synthesis time on the structure, crystallinity, morphology and surface area of the materials were studied in detail. Under this modified ultrasonic method, X-ray diffraction patterns of MIL-88A particles showed highly crystalline structures in contrast to those reported in literature. Significant differences on surface areas and microporosity were appreciated under ultrasound conditions employed. Specific surface areas in the range between 179 and 359 m2 g-1 were obtained. That material synthesized under ultrasound batch conditions during 1 h had the highest surface area and microporous character. Different particle sizes and morphologies were obtained depending on the synthesis procedure. In general, probe sonicators led to smaller particle sizes. Moreover, a comparative study of the ethylene adsorption of the MIL-88A particles and several common MOFs in the ethylene adsorption was investigated. The results suggest that the modified ultrasound-assisted procedure for the synthesis of MIL-88A is effective to obtain highly crystalline particles, which are very efficient to adsorb ethylene molecules.


Lack of cell loss following recurrent neonatal seizures.
In the neonatal rat recurrent seizures have been associated with long-term changes in cerebral excitability and cognition. Whether recurrent seizures in the neonatal rat lead to cell loss in the cerebral cortex is not known. We counted cells in the parietal cortex, piriform cortex, and CA3 and CA1 hippocampal subfields in young adult rats that had undergone a series of 55 seizures during the first 12 days of life. There were no differences in cell counts between the controls and rats subjected to neonatal seizures. Like the hippocampus, the neonatal pririform and parietal cortex is resistant to seizure-induced cell loss.


Retention of gene expression in porcine islets after agarose encapsulation and long-term culture.
Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expression profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture.


Inhibition of gamma-aminobutyric acid release from rat cerebral cortex slices by barbiturate anesthesia.
Amobarbital and pentobarbital anesthesia inhibited the potassium-stimulated, Ca-dependent release of gamma-aminobutyric acid (GABA) from rat cerebral cortex slices during incubation in vitro. Inhibition of GABA release was not found when slices were prepared from rats shortly after they awakened from amobarbital anesthesia. Phenobarbital anesthesia did not affect the release of GABA.


Structural and functional studies on Ribonuclease S, retro S and retro-inverso S peptides.
Ribonuclease S peptide and S protein offer a unique complementation system to understand the finer features of molecular recognition. In the present study the S peptide (1-16), and its retro and retro-inverso analogs have been analyzed for their structural and biological attributes. RPHPLC, CD, and NMR analyses have revealed that the physicochemical and conformational properties of the S peptide are distinct from those of its retro and retro-inverso analogs. On the functional side, while the S peptide complemented the S protein to give RNase activity, was recognized by anti-S peptide antibodies and induced T cell proliferation, neither the retro nor the retro-inverso S peptides could do so.