Characterisation and imaging of cortical impedance changes during interictal and ictal activity in the anaesthetised rat.
Epilepsy affects approximately 50 million people worldwide, and 20-30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex. Cortical impedance was recorded simultaneously to ECoG using a 30-contact electrode mat placed on the exposed cortex of anaesthetised rats, in which interictal spikes (IISs) and seizures were induced by cortical injection of 4-aminopyridine (4-AP), picrotoxin or penicillin. We characterised the tissue impedance responses during IISs and seizures, and imaged these responses in the cortex using Electrical Impedance Tomography (EIT). We found a fast, transient drop in impedance occurring as early as 12ms prior to the IISs, followed by a steep rise in impedance within ~120ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1mm in the cortex, and that they closely followed the activity propagation observed in the surface ECoG signals. The fast, pre-IIS impedance drop most likely reflects synchronised depolarisation in a localised network of neurons, and the post-IIS impedance increase reflects the subsequent shrinkage of extracellular space caused by the intense activity. EIT could also be used to picture a steady rise in tissue impedance during seizure activity, which has been previously described. Thus, our results demonstrate that EIT can detect and localise different physiological changes during interictal and ictal activity and, in conjunction with ECoG, may in future improve the localisation of seizure foci in the clinical setting.


Torticollis as a first sign of posterior fossa and cervical spinal cord tumors in children.
Torticollis, despite being well-known neurological manifestation, is often underestimated as a first symptom of the abnormalities of posterior cranial cavity and cervical spinal cord. The purpose of this study is to analyze the occurrence of acquired torticollis in children as a herald sign of the tumors of the cervical spinal cord or of the posterior fossa. Clinical records of 54 cases treated for the tumor of the cervical spinal cord or posterior fossa (including congenital ones) were retrospectively reviewed. The following data were calculated: the occurrence of the torticollis as a first sign of tumors, the duration time from the onset of the symptoms to diagnosis, the concurrence of other pathological symptoms, and the diminishing of symptoms of the torticollis following treatment. In 12/54 (22.2 %) torticollis was first sign of central nervous system tumor and in all of them preceded other neurological symptoms. The time from the onset of torticollis to establishing diagnosis ranged from 2 to 52 weeks (9.6 weeks on average). Eleven of twelve patients were treated surgically--in 10 of them, torticollis disappeared in the postoperative course. Torticollis may be a herald sign of the tumor of the cervical spinal cord or the posterior fossa. Those pathologies should be considered in the differential diagnosis of the torticollis, particularly if accompanied by other symptoms of the focal pathology of central nervous system. Awareness of this fact may shorten the time to establish the proper diagnosis. Torticollis necessitates exclusion of the posterior fossa and spinal cord tumor.


Do attitudes, intentions and actions of school food coordinators regarding public organic food procurement policy improve the eating environment at school? Results from the iPOPY study.
The present study investigates whether public organic food procurement policies have the potential to induce changes in the school food service environment. A comparative cross-national survey was conducted in public primary and/or secondary schools in Finland, Germany and Italy. The school food coordinators completed a web-based questionnaire on their attitudes, intentions and actions towards organic school food provision. In Germany, 122 out of 2050 schools in the state of Hesse responded. In Finland, 250 out of 998 schools across the country responded. In Italy, 215 out of 940 schools from eight provinces responded. School food coordinators in the sample of schools in the three countries. The German and Finnish school food coordinators separately most agreed with the promotion of healthy eating habits (P < 0·001) and organic food (P < 0·001) by schools. The Finnish schools were most likely to adopt a food and nutrition policy (P < 0·001), a health-promoting school policy according to WHO principles (P < 0·001), to have a playground (P < 0·001), to involve physical activity themes in teaching (P = 0·012) and to have a canteen (P < 0·001). The Italian schools were most likely to involve the food and nutrition policy in pedagogical activities (P = 0·004), to serve nutritional school meals (P < 0·001) and to recommend children to eat healthily (P < 0·001). In the three countries, the non-organic schools were less likely to adopt a food and nutrition policy (P < 0·001), a WHO health-promoting policy (P < 0·001) and have a canteen (P = 0·017) than the organic schools. The study suggests that there is a gap in the effects of public organic food procurement policy on building a healthier school food environment.


Inhibition of ornithine decarboxylase potentiates nitric oxide production in LPS-activated J774 cells.
We have examined whether modulation of the polyamine biosynthetic pathway, through inhibition by alpha-difluoromethylornithine (DFMO) of the rate limiting enzyme, ornithine decarboxylase (ODC), modulates NO synthesis in J774 macrophages. DFMO potentiated LPS-stimulated nitrite production in both a concentration- and time-dependent manner, increasing nitrite levels by 48+/-5% at 10 mM. This effect was observed in cells pre-treated with DFMO for 24 h prior to stimulation with LPS. Addition of DFMO 12 h after LPS failed to potentiate LPS-induced nitrite production. Supplementation of the culture medium with horse serum (10%) in place of foetal calf serum (10%) caused no significant change in either LPS-induced nitrite production or in the ability of DFMO (10 mM) to potentiate LPS-induced NO synthesis. Metabolism of L-[3H]arginine to L-[3H]citrulline by partially purified inducible nitric oxide synthase (iNOS) was not significantly altered by either DFMO (1-10 mM) or by putrescine (0.001-1 mM), spermidine (0.001-1 mM) or spermine (0.001-1 mM). iNOS activity was also unaffected by 1 mM EGTA but was markedly attenuated (70+/-0.07%) by L-NMMA (100 microM). Pre-incubation of cells with DFMO (10 mM; 24 h) prior to activation with LPS resulted in enhanced (approximately 2 fold) iNOS protein expression. These results show that DFMO potentiates LPS-induced nitrite production in the murine macrophage cell line J774. Since the only known mechanism of action of DFMO is inhibition of ODC, and thus polyamine biosynthesis, we conclude that expression of iNOS can be critically regulated by endogenous polyamines.


Cerebellar Grey Matter Volume in Older Persons Is Associated with Worse Cognitive Functioning.
The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e. symptoms of depression and apathy) and general daily functioning in a population of community-dwelling older persons with mild cognitive deficits, but without dementia. In 194 participants of the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden, the association between cerebellar GMV, WMHs, LIs and MBs and measures of cognitive, psychological and general daily functioning was analysed with linear regression analysis, adjusted for age, sex, education and cerebral volume. Cerebellar GMV was associated with the overall cognition score (standardised beta 0.20 [95% CI, 0.06-0.33]). Specifically, posterior cerebellar GMV was associated with executive function (standardised beta 0.18 [95% CI, 0.03-0.16]). No relation was found between vascular pathology and cognition. Also, no consistent associations were found on the cerebellar GMV and vascular pathology measures and psychological and general daily functioning. In this population of community-dwelling elderly, less posterior cerebellar GMV but not vascular pathology was associated with worse cognitive function, specifically with poorer executive function. No relation was found between cerebellar pathology and psychological and general daily functioning.


Multimorbidity, polypharmacy, and drug-drug-gene interactions following a non-ST elevation acute coronary syndrome: analysis of a multicentre observational study.
The number of patients living with co-existing diseases is growing. This study aimed to assess the extent of multimorbidity, medication use, and drug- and gene-based interactions in patients following a non-ST elevation acute coronary syndrome (NSTE-ACS). In 1456 patients discharged from hospital for a NSTE-ACS, comorbidities and multimorbidity (≥ 2 chronic conditions) were assessed. Of these, 698 had complete drug use recorded at discharge, and 652 (the 'interaction' cohort) had drug use and actionable genotypes available for CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, DPYD, F5, SLCO1B1, TPMT, UGT1A1, and VKORC1. The following drug interactions were investigated: pharmacokinetic drug-drug (DDIs) involving CYPs (CYPs above, plus CYP1A2, CYP2C8, CYP3A4), SLCO1B1, and P-glycoprotein; drug-gene (DGIs); drug-drug-gene (DDGIs); and drug-gene-gene (DGGIs). Interactions predicted to be 'substantial' were defined as follows: DDIs due to strong inhibitors/inducers, DGIs due to variant homozygous/compound heterozygous genotypes, and DDGIs/DGGIs where the constituent DDI/DGI(s) both influenced the victim drug in the same direction. In the whole cohort, 727 (49.9%) patients had multimorbidity. Non-linear relationships between age and increasing comorbidities and decreasing coronary intervention were observed. There were 98.1% and 39.8% patients on ≥ 5 and ≥ 10 drugs, respectively (from n = 698); women received more non-cardiovascular drugs than men (median (IQR) 3 (1-5) vs 2 (1-4), p = 0.014). Overall, 98.7% patients had at least one actionable genotype. Within the interaction cohort, 882 interactions were identified in 503 patients (77.1%), of which 346 in 252 patients (38.7%) were substantial: 59.2%, 11.6%, 26.3%, and 2.9% substantial interactions were DDIs, DGIs, DDGIs, and DGGIs, respectively. CYP2C19 (49.5% of all interactions) and SLCO1B1 (18.4%) were involved in the largest number of interactions. Multimorbidity (p = 0.019) and number of drugs (p = 9.8 × 10-10) were both associated with patients having ≥ 1 substantial interaction. Multimorbidity (HR 1.76, 95% CI 1.10-2.82, p = 0.019), number of drugs (HR 1.10, 95% CI 1.04-1.16, p = 1.2 × 10-3), and age (HR 1.05, 95% CI 1.03-1.07, p = 8.9 × 10-7), but not drug interactions, were associated with increased subsequent major adverse cardiovascular events. Multimorbidity, polypharmacy, and drug interactions are common after a NSTE-ACS. Replication of results is required; however, the high prevalence of DDGIs suggests integrating co-medications with genetic data will improve medicines optimisation.


Toll-like receptor 4 inhibitor protects against retinal ganglion cell damage induced by optic nerve crush in mice.
Toll-like receptor 4 (TLR4) plays key roles in innate immune responses and inflammatory reactions. TAK-242 (resatorvid) is a small-molecule cyclohexene derivative that selectively inhibits TLR4 signaling pathways and suppresses inflammatory reactions. Here we investigated the protective effects of TAK-242 against optic nerve crush (ONC) which induces axonal injury like glaucoma in mice. TAK-242 was injected intravitreally immediately after ONC. The effect of TAK-242 was evaluated by measuring the number of fluorogold-labeled retinal ganglion cells (RGCs) at 10 days after ONC. Furthermore, the expression levels of phosphorylated-nuclear factor-kappa B (p-NF-κB) and phosphorylated-p38 (p-p38) were measured by Western blotting. In addition, we examined activated astrocytes by immunostaining. TAK-242 significantly abrogated the loss of RGCs associated with ONC. Moreover, the expression levels of p-NF-κB and p-p38 were significantly reduced by TAK-242 treatment. Furthermore, TAK-242 and C34, a TLR4 inhibitor, significantly reduced astrocyte activation in the ganglion cell and inner plexiform layers, compared with vehicle treatment. These findings indicate that TAK-242 inhibits not only the TLR4 signaling pathway but also astrocyte activation downstream of this pathway, suggesting that the inhibition of TLR4 signaling is a promising candidate for the treatment of glaucoma.


Co-delivery of ccl19 gene enhances anti-caries DNA vaccine pCIA-P immunogenicity in mice by increasing dendritic cell migration to secondary lymphoid tissues.
To investigate how co-delivery of the gene encoding C-C chemokine ligand-19 (CCL-19) affected the systemic immune responses to an anti-caries DNA vaccine pCIA-P in mice. Plasmid encoding CCL19-GFP fusion protein (pCCL19/GFP) was constructed by inserting murine ccl19 gene into GFP-expressing vector pAcGFP1-N1. Chemotactic effect of the fusion protein on murine dendritic cells (DCs) was assessed in vitro and in vivo using transwell and flow cytometric analysis, respectively. BALB/c mice were administered anti-caries DNA vaccine pCIA-P plus pCCL19/GFP (each 100 μg, im) or pCIA-P alone. Serum level of anti-PAc IgG was assessed with ELISA. Splenocytes from the mice were stimulated with PAc protein for 48 h, and IFN-γ and IL-4 production was measured with ELISA. The presence of pCCL19/GFP in spleen and draining lymph nodes was assessed using PCR. The expression of pCCL19/GFP protein in these tissues was analyzed under microscope and with flow cytometry. The expression level of CCL19-GFP fusion protein was considerably increased 48 h after transfection of COS-7 cells with pCCL19/GFP plasmids. The fusion protein showed potent chemotactic activity on DCs in vitro. The level of serum PAc-specific IgG was significantly increased from 4 to 14 weeks in the mice vaccinated with pCIA-P plus pCCL19/GFP. Compared to mice vaccinated with pCIA-P alone, the splenocytes from mice vaccinated with pCIA-P plus pCCL19/GFP produced significantly higher level of IFN-γ, but IL-4 production had no significant change. Following intromuscular co-delivery, pCCL19/GFP plasmid and fusion protein were detected in the spleen and draining lymph nodes. Administration of CCL19 gene in mice markedly increased the number of mature DCs in secondary lymphoid tissues. CCL19 serves as an effective adjuvant for anti-caries DNA vaccine by inducing chemotactic migration of DCs to secondary lymphoid tissues.


Marginal opening of single and twin platinum foil-bonded aluminous porcelain crowns.
The marginal openings of single and twin foil-bonded aluminous porcelain crowns were compared in crowns fabricated indirectly for extracted teeth and directly on typodont teeth. The crowns were cemented with zinc phosphate, embedded in plastic, and sectioned. Marginal opening was measured directly with a traveling microscope. There was no significant difference between the marginal openings of twin- and single-foil crowns fabricated indirectly for extracted teeth. When the crowns were constructed directly on typodont teeth to eliminate the variables of impression-making and die fabrication, the single-foil crowns possessed a significantly smaller marginal opening than the twin-foil crowns. Both the twin- and single-foil complete porcelain crowns resulted in clinically acceptable margins. The single-foil crowns were easier to make.


The effect of scalp cooling on CIA-related quality of life in breast cancer patients: a systematic review.
Chemotherapy-induced alopecia (CIA) remains a distressing adverse event of cancer treatment but may be prevented by scalp cooling. The effectiveness of scalp cooling, however, is dependent on the chemotherapy regimen with successful hair preservation (i.e., < 50% hair loss) in 41-59% of women on taxane-based therapies in comparison to 16-36% on anthracycline-based therapies. Despite the potential utility, use of scalp cooling has shown a more equivocal impact on quality of life (QoL). In this review, we aim to evaluate the use of scalp cooling for CIA and quantitative QoL measures. A systematic review of PubMed, Embase, Web of Science, and Cochrane databases for clinical studies on scalp cooling to prevent CIA published before October 29, 2018 was performed. Clinical studies with 5 or more patients that reported on a quantitative QoL measure were included and graded according to a modified five-point scale from the Oxford Centre for Evidence-Based Medicine. Studies meeting inclusion criteria included 4 randomized clinical trials (RCT), 8 cohort studies, and 1 cross-sectional study with 1282 unique patients. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30: 46%) and Breast Cancer Module (QLQ-BR23: 46%) represented the most commonly used QoL assessments. Overall, 4 (31%) of the 13 studies concluded that scalp cooling was associated with significant improvements in QoL measures; 8 (62%) determined that there was either non-significant or no improvements; and 1 (7.7%) provided a mixed conclusion. Although 2 (50%) RCT demonstrated that scalp cooling can effectively prevent CIA depending on the chemotherapy regimen, these studies did not show that successful hair preservation was associated with improved QoL measures. This review demonstrates that scalp cooling is not consistently associated with significant QoL improvements as assessed by EORTC QLQ-C30 and -BR23. Representing a critical limitation, more than one-third of the studies did not subcategorize QoL outcomes for successfully or unsuccessfully scalp-cooled patients but rather reported on QoL measures for all scalp-cooled patients in general. Failure to prevent hair loss in patients undergoing an expensive and potentially uncomfortable treatment likely contributes to decreased well-being, impacting the overall distribution of QoL measures in scalp cooling patients compared to controls. Future studies should incorporate validated QoL instruments specific to hair disease and classify QoL outcomes for scalp-cooled patients based on the degree of hair preservation.


Comparison of therapeutic efficacy and host toxicity of two different 131I-labelled antibodies and their fragments in the GW-39 colonic cancer xenograft model.
The in vivo uptake, therapeutic potential, and host toxicity were evaluated for both the intact IgG and F(ab')2 fragment of 2 murine monoclonal antibodies (MAbs) directed against either carcino-embryonic antigen (CEA), called NP-4, or colon-specific antigen-p (CSAp), called Mu-9, in the GW-39 human colorectal carcinoma grown in the hamster cheek pouch. Mu-9 IgG and F(ab')2 were retained longer by the tumor than was the NP-4 IgG or F(ab')2, respectively. Localization of the two antibodies by micro-autoradiography revealed two distinct patterns. Mu-9 was seen densely around whole acini of tumor cells, whereas NP-4 was found around each individual cell, albeit less densely. The anti-tumor effects of 131I-labelled Mu-9 and NP-4 IgG were equal, but the therapeutic effectiveness of Mu-9 F(ab')2 was significantly higher than NP-4 F(ab')2, as measured by change in tumor size. A dose-dependent increase in host toxicity, as measured by change in body weight and change in peripheral white blood cells (p-WBCs), was observed with 0.5 to 3.0 mCi doses of 131I-IgG regardless of the MAb used. A 10-22% loss in body weight lasting 3-7 weeks and a 50-80% loss in pWBCs lasting 6-8 weeks were observed in these animals. In contrast, 3 x 2 mCi doses of 131I-NP-4 or Mu-9 F(ab')2 given at 3-day intervals, a schedule which was equally therapeutic to a single 2-mCi dose of 131I-IgG, resulted in only a 9% loss in body weight and a 50% loss in pWBCs that lasted only 1 week. This was followed by a complete recovery over the next 2-3 weeks. These data suggest that multiple doses of F(ab')2 can be as tumoricidal as a single dose of an intact MAb IgG, but significantly less toxic to the host.


Heterochromatin Protein 1: A Multiplayer in Cancer Progression.
Dysregulation of epigenetic mechanisms as well as genomic mutations contribute to the initiation and progression of cancer. In addition to histone code writers, including histone lysine methyltransferase (KMT), and histone code erasers, including histone lysine demethylase (KDM), histone code reader proteins such as HP1 are associated with abnormal chromatin regulation in human diseases. Heterochromatin protein 1 (HP1) recognizes histone H3 lysine 9 methylation and broadly affects chromatin biology, such as heterochromatin formation and maintenance, transcriptional regulation, DNA repair, chromatin remodeling, and chromosomal segregation. Molecular functions of HP1 proteins have been extensively studied, although their exact roles in diseases require further study. Here, we comprehensively review the studies that have revealed the altered expression of HP1 and its functions in tumorigenesis. In particular, the distinctive effects of each HP1 subtype, namely HP1α, HP1β, and HP1γ, have been thoroughly explored in various cancer types. We also highlight how HP1 can serve as a potential biomarker for cancer prognosis and therapeutic target for cancer patients.


Anti-cancer peptide-based therapeutic strategies in solid tumors.
Nowadays, conventional medical treatments such as surgery, radiotherapy, and chemotherapy cannot cure all types of cancer. A promising approach to treat solid tumors is the use of tumor-targeting peptides to deliver drugs or active agents selectively. Introducing beneficial therapeutic approaches, such as therapeutic peptides and their varied methods of action against tumor cells, can aid researchers in the discovery of novel peptides for cancer treatment. The biomedical applications of therapeutic peptides are highly interesting. These peptides, owing to their high selectivity, specificity, small dimensions, high biocompatibility, and easy modification, provide good opportunities for targeted drug delivery. In recent years, peptides have shown considerable promise as therapeutics or targeting ligands in cancer research and nanotechnology. This study reviews a variety of therapeutic peptides and targeting ligands in cancer therapy. Initially, three types of tumor-homing and cell-penetrating peptides (CPPs) are described, and then their applications in breast, glioma, colorectal, and melanoma cancer research are discussed.


Using the "2 standard deviations" rule with Dixon MRI to differentiate renal cell carcinoma types.
Clear cell and non-clear cell renal cell carcinoma (RCC) are distinguishable based on microscopic fat, detectable by chemical shift MRI. However, these assessments are often subjective. Conversely, Dixon MRIs and the "2 standard deviations" rule (2SDR) are quantitative methods that may decrease diagnostic subjectivity. Therefore, this study assessed the value of the 2SDR for detecting microscopic fat and thus differentiating clear cell and non-clear cell RCC using Dixon MRI. This retrospective study included patients with RCC who underwent preoperative Dixon MRI. The patients were grouped based on tumor type: clear cell RCC and non-clear cell RCC. The 2SDR value was calculated based on in-phase and opposed-phase images and then compared between the two groups. 2SDR values >0 indicated clear cell RCCs, whereas values <0 indicated non-clear cell RCC. We included 151 patients; 114 patients had clear cell RCC, of which 106 had a 2SDR value >0. Furthermore, 37 patients had non-clear cell RCC, of which 3 had a 2SDR value >0. The 2SDR value was significantly higher in the clear cell RCC group than in the non-clear cell RCC group (p = 0.000). Overall, 93.0% (106/114) and 8.1% (3/37) of patients with clear cell and non-clear cell RCC, respectively, had microscopic fat. The evaluation indices for this 2SDR method were: accuracy: 92.72%, sensitivity: 92.98%, specificity: 91.89%, positive predictive value: 97.25%, and negative predictive value: 80.95%. 2SDR values calculated from Dixon magnetic resonance images can differentiate clear cell from non-clear cell RCCs by detecting microscopic fat. The "2 standard deviations" rule value calculated from Dixon MR images differentiates clear cell from non-clear cell renal cell carcinoma with high efficiency by detecting microscopic fat.


Chiral metal-organic frameworks and their composites as stationary phases for liquid chromatography chiral separation: A minireview.
Chiral metal organic frameworks (CMOFs) are a kind of crystal porous framework material that has attracted increasing attention due to the customizable combination of metal nodes and organic ligands. In particular, the highly ordered crystal structure and rich adjustable chiral structure make it a promising material for developing new chiral separation material systems. In this review, the progress of CMOFs and their different types of composites used as chiral stationary phases (CSPs) in liquid chromatography for enantioseparation are discussed. The characteristics of CMOFs and their composites are summarized, aiming to provide new ideas for the development of CMOFs with better performance and further promote the application of CMOFs materials in enantioselective high-performance liquid chromatography (HPLC).


Should I stay or should I go: Can air pollution reduce the health benefits of physical exercise?
The urbanization process resulted in incredible achievements for society, unfortunately together with economic, social, and technological development it deteriorates air quality and encourages sedentary behavior. Air pollution inhalation is responsible for a massive negative health effect. The practice of regular physical exercise is strongly encouraged to achieve a healthy lifestyle. However, particularly during a physical exercise session, the respiratory system undergoes some physiological adaptations that lead to an increase in the volume of inhaled air, so exercising in a polluted environment would consequently augment the number of pollutants inhaled. In this scenario, would it be safer to stay physically inactive? Or to choose an indoor facility to exercise? Or to keep performing outdoor activities once the benefits achieved with exercise will overcome the possible damage caused by additional exposure to air pollution? Currently, these questions still do not have a decisive answer, so we designed a hypothesis to be tested in which exercise would be beneficial regardless of the chosen place. Outdoor and indoor pollution are both equally harmful to health, however, we do not know if it would have a difference to exercise in one of them.


Biochemical characterization of the eta chain of the T-cell receptor. A unique subunit related to zeta.
The T-cell antigen receptor is a multisubunit complex consisting of at least seven chains. Based upon structural and genetic considerations, we have divided these chains into three groups. The alpha and beta subunits (Ti) are the clonotypic chains responsible for antigen recognition. Three chains that are invariant among all T-cells define the CD3 complex. These include the CD3 gamma, delta, and epsilon chains. The zeta chain is a distinct component that, like the CD3 chains, is invariant among all T-cells. In the majority of receptors, zeta is found as a disulfide-linked homodimer. We have recently shown that approximately 10% of zeta is disulfide-linked to a chain which we have called eta. A preliminary model has been proposed, suggesting that there are two subclasses of receptors, depending upon the presence within the complex of either the zeta-zeta homodimer or the zeta-eta heterodimer. Evidence has been presented that these two subclasses may perform distinct signaling functions. In this paper the eta chain is characterized to determine whether it is structurally related to the zeta chain and, in particular, whether it might represent a post-translational modification of zeta. We can identify specific antigenic epitopes that are shared by both zeta and eta. However, not all antibodies raised against zeta can directly recognize eta. The apparent molecular mass of eta is 22 kDa, whereas zeta has a molecular mass of 16 kDa. We are unable to demonstrate any post-translational covalent modifications of eta to explain the difference in apparent molecular weight. These include phosphorylation, glycosylation, or sulfation. Amino acid incorporation studies demonstrate that the amino acid composition of eta is distinct from that of zeta. All of the eta in a T-cell is found in association with the rest of the components of the T-cell receptor. In addition, our anti-eta antibodies allow us to directly recognize human eta, which has an apparent molecular mass of approximately 23 kDa. Thus, eta and zeta appear to be related but distinct proteins, and we would propose that eta is the second member of the zeta group of components of the T-cell receptor.


Computed tomographic features of round atelectasis.
Computed tomography (CT) of the chest is often variable in the evaluation of pulmonary masses. Our case demonstrated characteristic findings on CT that aided in the diagnosis of round atelectasis.


A case of the blues: Inadvertent ocular injury from accidental instillation of blue ink.
Many consumer products and non-ophthalmic medications are packaged in plastic "eye dropper" bottles, posing a risk of accidental ocular chemical injury when these substances are mistaken for eye drops. We present the case of an elderly glaucoma patient who mistook blue stamper ink for the glaucoma medication Combigan®, and suffered ocular injury as a result. The packaging of non-ophthalmic products in plastic "eye dropper" bottles poses a significant risk of accidental ocular chemical injury. Elderly individuals with low vision and/or cognitive deficits may be at particular risk of accidental injury. Ophthalmologists have been calling for a greater distinction between the packaging of ophthalmic and non-ophthalmic products for over 35 years, but to date little progress has been made in this regard.


Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects.
Transplantation of mesenchymal stem cells (MSCs) is one possible strategy to achieve articular cartilage repair. We previously reported that synovial MSCs were highly proliferative and able to undergo chondrogenesis. We also found that placing a suspension of synovial MSCs on a cartilage defect for 10 minutes promoted cartilage repair in rabbit and pig models. However, the in vivo efficacy of this approach has not been tested clinically. We asked whether transplantation of synovial MSCs improves (1) MRI features, (2) histologic features, and (3) clinical evaluation scores in patients with cartilage defects in the knee? Patients with a symptomatic single cartilage lesion of the femoral condyle were indicated for inclusion in our study, and between April 2008 and April 2011, 10 patients were enrolled in this study. All patients completed followups of 3 years or more. The average followup period was 52 months (range, 37-80 months). Synovial MSCs were expanded with 10% autologous human serum for 14 days after digestion. For transplantation, the patient was positioned so that the cartilage defect was facing upward, and synovial MSC suspension was placed on the cartilage defect with a syringe under arthroscopic control. The defect with the applied suspension then was held in the upward position for 10 minutes. Five patients underwent concomitant ACL reconstructions, among whom two had meniscus suturing performed simultaneously. For MRI quantification, the cartilage defect was scored from 0 to 5. Second-look arthroscopy was performed for four patients and biopsy specimens were evaluated histologically. Clinical outcome was assessed using the Lysholm score and Tegner Activity Level Scale at final followup. Comparisons of MRI and Lysholm scores before and after treatment for each patient were analyzed using the Wilcoxon signed-rank test. MRI score (median ± 95% CI) was 1.0 ± 0.3 before and 5.0 ± 0.7 after, and increased after treatment in each patient (p = 0.005). Second-look arthroscopy in four patients showed that the cartilage defect appeared to be qualitatively better in all cases. Histologic analyses showed hyaline cartilage in three patients and fibrous cartilage in one at the deep zone. The Lysholm score (median ± 95% CI) was 76 ± 7 before and 95 ± 3 after, and increased after treatment in each patient (p = 0.005). The Tegner Activity Level Scale did not decrease after treatment in each patient. For this small initial case series, transplantation of synovial MSCs was effective in terms of MRI score, qualitative histology, and Lysholm score. The use of synovial MSCs has an advantage in that the cells can be prepared at passage 0 in only 14 days. Transplantation of synovial MSCs may be less invasive than mosaicplasty and autologous chondrocyte implantation. To conclusively show the effectiveness of this treatment requires comparative studies, especially with more established arthroscopic procedures, such as marrow stimulation techniques. Level IV, therapeutic study.


Effect of the number of unhealthy lifestyles in middle-aged and elderly people on hypertension and the first occurrence of ischemic stroke after the disease.
To determine the relationship between the number of controllable unhealthy lifestyles on the risk of the first occurrence of ischemic stroke after the disease in middle-aged and elderly people in the community, and to provide data support and basis for community physicians to guide hypertensive patients to control modifiable risk factors to prevent the first occurrence of ischemic stroke. The relationship between the number of unhealthy lifestyles and the risk of hypertension was analyzed by binary logistic regression in 584 subjects using a medical record control study. A retrospective cohort study of 629 hypertensive patients was used to analyze the relationship between the number of unhealthy lifestyles and the risk of the first occurrence of ischemic stroke within 5 years of developing hypertensive disease using Cox proportional risk regression models. Logistic regression model analysis showed that taking an unhealthy lifestyle as a reference, the OR (95% CI) values of, 2, 3, 4 and 5 unhealthy lifestyle were 4.050 (2.595-6.324), 4 (2.251-7.108), 9.297 (3.81-22.686), and 16.806 (4.388-64.365), respectively. Cox Proportional risk regression model analysis showed that the risk of ischemic stroke within 5 years after developing hypertension was referenced to 5 unhealthy lifestyles, and the HR (95% CI) for 3, 2, and 1 unhealthy lifestyle were 0.134 (0.023-0.793), 0.118 (0.025-0.564), and 0.046 (0.008-0.256), respectively. The number of controllable unhealthy lifestyles in middle-aged and elderly people was positively associated with the risk of hypertension and first ischemic stroke after hypertension, and there was a dose-effect relationship between them. The risk of hypertension and first ischemic stroke within 5 years after hypertension onset increased with the number of unhealthy lifestyles.


TAK1 inhibition prevents the development of autoimmune diabetes in NOD mice.
Transforming growth factor-β activated kinase-1 (TAK1, Map3k7), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, is essential in innate and adaptive immune responses. We postulated that blockade of TAK1 would affect autoimmune diabetes in non-obese diabetic (NOD) mice. Administration of 5Z-7-oxozeaenol (OZ), a TAK1 inhibitor, decreased the incidence and delayed the onset of autoimmune diabetes in both spontaneous and accelerated (cyclophosphamide-induced) experimental NOD mice. OZ also reduced insulitis, preserved islet function, increased the expression of α1- antitrypsin (AAT), and severely inhibited NF-κB and JNK/AP-1 signaling pathways in immune organs and pancreatic tissues. Importantly, TAK1 inhibition by OZ elicited a Th1 to Th2 cytokine shift, and increased TGF-β1 production in cultured T lymphocytes supernatants. Systemic TAK1 inhibition induced immature DCs with lower expressions of MHC-II and CD86, attenuated DC-mediated T cell proliferation in allogeneic MLR, and production of cytokine IL-12p70 in DCs suspensions. The results indicate that TAK1 inhibition with OZ was associated with a lower frequency of autoimmune diabetes in NOD mice. The net effect of TAK1 inhibition in NOD mice therefore appears to be protective rather than disease-enhancing. Strategies targeting TAK1 specifically in NOD mice might prove useful for the treatment of autoimmune diabetes in general.


Statistical procedures for assignments of upper bounds for radiation doses to an unbadged individual in a group for which some individuals are badged.
Consider a group of individuals exposed to radiation for an interval of time, such as units of military personnel during nuclear weapons tests three and four decades ago. Often, dosimetry information is known for several, but not all, individuals of that group. A nonparametric procedure is described that gives probability-based, upper-bound estimates of doses for an unbadged individual (within the group) for whom dose information is required; such information is useful in litigation. The method is illustrated by an application to a Navy unit.


A simple and sensitive flow injection method based on the catalytic activity of CdS quantum dots in an acidic permanganate chemiluminescence system for determination of formaldehyde in water and wastewater.
A simple and sensitive flow injection chemiluminescence (CL) method in which CdS quantum dots (QDs) enhanced the CL intensity of a KMnO4-formaldehyde (HCHO) reaction was offered for the determination of HCHO. This CL system was based on the catalytic activity of CdS QDs and their participation in the CL resonance energy transfer (CRET) phenomenon. A possible mechanism for the supplied CL system was proposed using the kinetic curves of the CL systems and the spectra of CL, photoluminescence (PL) and ultraviolet-visible (UV-Vis). The emanated CL intensity of the KMnO4-CdS QDs system was amplified in the presence of a trace level of HCHO. Based on this enhancement effect, a simple and sensitive flow injection CL method was suggested for the determination of HCHO concentration in environmental water and wastewater samples. Under selected optimized experimental conditions, the increased CL intensity was proportional to the HCHO concentration in the range of 0.03-4.5 μg L(-1) and 4.5-10.0 μg L(-1). The detection limits (3σ) were 0.0003 μg L(-1) and 1.2 μg L(-1). The relative standard deviations (RSD%) for eleven replicate determinations of 4.0 μg L(-1) HCHO were 2.2%. Furthermore, the feasibility of the developed method was investigated via the determination of HCHO concentration in environmental water and wastewater samples.


Clinical features of maternal uniparental disomy 14 in patients with an epimutation and a deletion of the imprinted DLK1/GTL2 gene cluster.
Maternal uniparental disomy 14 [upd(14)mat] is associated with a recognizable phenotype that includes pre- and postnatal growth retardation, neonatal hypotonia, feeding problems and precocious puberty. Chromosome 14 contains an imprinted gene cluster, which is regulated by a differentially methylated region (IG-DMR) between DLK1 and GTL2. Here we report on four patients with clinical features of upd(14)mat who show a maternal-only methylation pattern, but biparental inheritance for chromosome 14. In three of the patients loss of paternal methylation appears to be a primary epimutation, whereas the other patient has a paternally derived deletion of -1 Mb that includes the imprinted DLK1-GTL2 gene cluster. These findings demonstrate that the upd(14)mat phenotype is caused by altered expression of genes within this cluster.


Bacterial contamination of blood products: factors, options, and insights.
Transfusion of bacterially contaminated blood products remains an overlooked problem. However, the risk of receiving a bacterially contaminated unit is greater than the combined risk of HIV-1/2, HCV, HBV, and HTLV I/II [American Association of Blood Banks Bulletin, no. 294, 1996]. Topics covered in this article include: the current incidence, clinical presentation and outcome, effective methods of detection, and ways to reduce bacterial contamination of blood products. There is no one existing strategy that can completely eliminate the risk of bacterial contamination. It is inevitable that partial solutions or combinations of methods will be implemented in the near future.


Surgical therapy of Zenker's diverticulum: low risk and high efficiency.
Surgery for the treatment of Zenker's diverticulum was performed at our institution in a total of 43 patients over 6 1/2 years. Cervical myotomy with diverticulectomy was performed in 32 of the patients and myotomy alone in 11. Mortality totaled 0%, with a reversible lesion of the recurrent nerve occurring in 7%. In 60% of the cases investigated preoperatively (N = 40), motility disorders of the upper esophageal sphincter (UES) could be demonstrated using manometry as well as with cineradiography in 92% of the patients. Follow-up studies in 39 of the cases 25 months (mean) postprocedure indicated 82% of the patients to be symptom-free, with the remaining 18% demonstrating a marked improvement. Postoperative manometry as well as cineradiography carried out in 12 patients revealed the presence of UES motility dyscoordination in 8% and 25%, respectively. There were, however, no signs of recurrence of the diverticulum. The high number of patients in our study group demonstrating motility disorders of the UES emphasizes the need for cervical myotomy as part of the surgical therapy for Zenker's diverticulum.


Capillaria hepatica infection in coyotes of Louisiana.
Capillaria hepatica infection was diagnosed by histologic examination in 21 of 71 (30%) coyotes in Louisiana. All infected coyotes were at least 1 year old, and most (19 of 21) were more than 2 year years old. Capillaria hepatica was not found in any livers from 31 red foxes and 20 gray foxes examined.


Genetic analysis and regulation of the Rhizobium meliloti genes controlling C4-dicarboxylic acid transport.
The genes controlling the transport of C4-dicarboxylic acids from Rhizobium meliloti have been cloned and analysed. The nucleotide sequence of the control region of the structural dctA and the regulatory dctBD genes has been determined. Comparison with the Rhizobium leguminosarum dct genes revealed a high degree of homology. Gene fusions to the enteric lacZY reporter gene were constructed and the expression of the dctA and dctBD genes studied under various physiological conditions. In free-living cells, the regulatory dctBD genes are absolutely required for the expression of the dctA gene. In the root nodule environment, a dctA::lacZY gene fusion was found to be expressed in an R. meliloti strain mutated in both the dctB and dctD genes, but not in a strain mutated in the dctB gene alone. The presence of the conserved upstream NifA-binding sites on the dctA promoter sequence, coupled with the fact that the dctA::lacZY gene fusion is not expressed in root nodules formed by a nifA mutant strain of R. meliloti, supports the suggestion that NifA may be involved in the symbiotic expression of dctA in the absence of the regulatory dctBD genes. Under micro-aerobic conditions, however, NifA induction alone is not sufficient for expression of the dctA promoter, even though the NifA-dependent nifHDK promoter is highly expressed under these conditions.


Characterization of the submandibular gland microsomal calcium transport system.
Calcium accumulation by submandibular gland microsomes (first described by Selinger and Naim, ((1970) Biochim. Biophys. Acta 323, 337-341) has been further characterized. Accumulation was concentration dependent, had a Km of 25 microM added calcium and a Vmax of 12 nM calcium/mg protein per min. No accumulation was observed in the presence of either the calcium ionophore A23187, or the detergent Triton X-100 (0.05). The divalent cations Sr2+ and Mn2+ inhibited accumulation competitively with Ki values of 67 microM and 200 microM, respectively. The effect of various enzyme inhibitors were tested on the microsomal calcium transport system and it was found that chlorpromazine, trifluoperazine, and DIDS all inhibited. The mitochondrial transport inhibitors ruthenium red and CCCP had no effect on transport. Experiments directed at clarifying the cellular location of the system are described. It was found that the membrane vesicles responsible for transport show different purification properties than the membrane vesicles which contain the standard enzyme markers for total and rough endoplasmic reticulum, Golgi apparatus, plasma membrane, and lysosomes. These conclusions are based upon experiments using these properties for membrane purification, density, size, and electrophoretic mobility. Three possible explanations of the results are given and it is organelles. The significance of the results in: (1) understanding the biochemical properties of the submandibular gland microsomal calcium transport system, (2) clarifying the cellular location of the system, and (3) clarifying the function of the system in salivary secretion are discussed.


Rat Model of Trigeminal Neuralgia Using Cobra Venom Mimics the Electron Microscopy, Behavioral, and Anticonvulsant Drug Responses Seen in Patients.
A new animal model of trigeminal neuralgia produced by injecting cobra venom into the infraorbital nerve (ION) trunk in rats had been developed. We tested and extended the model by observing the ultrastructural alterations of neurons and ameliorative effect of pregabalin in cobra venom-induced pain behaviors of rats. The goal of this study was to prove the feasibility of the cobra venom-induced model of trigeminal neuralgia and to demonstrate the demyelination change of ION and medulla oblongata is the major pathological change of trigeminal neuralgia. An experimental study. Department of Anesthesiology, Pain Medicine, and Critical Care Medicine, Aviation General Hospital of China Medical University. Experiments were carried out on male Sprague-Dawley rats. Video recordings were taken after the cobra venom injection and pregabalin administration. Ultrastructural alterations of ION and medulla oblongata were observed at the electron microscopic level. We also observed alteration in pain behaviors by analysis of video recordings. Compared to the preoperative and sham-operated group rats, experimental group rats exhibited significant changes in exploratory, resting, face-grooming, and head-shake behaviors on 3, 7, 14 days after operation (P < 0.01). The demyelination changes of ION and medulla oblongata were evident after administration of cobra venom to the ION. Compared to the pre-treated (no pregabalin administration) and control group rats, pregabalin group rats showed profound changes in exploratory, resting, face-grooming, and head-shake behaviors throughout the 14 day study period after treatment with drugs (P < 0.01). Ultrastructural alterations of ION and medulla oblongata were not examined after the treatment with pregabalin. Video recordings of free behaviors and pregabalin application prove the feasibility of the rat model of trigeminal neuralgia. The results of electron micrographs are consistent with a previous study in humans showing that the demyelination change of axons is the major pathological change of trigeminal neuralgia. The central demyelination alterations may explain why the mechanical threshold was found to be decreased on the non-operated side of experimental animals.


Characterization of a cloned xenopus laevis serotonin 5-HT1A receptor expressed in the NIH-3T3 cell line.
In a previous work we isolated a Xenopus 5-HT1A receptor gene and now report the characterization of this receptor. The HindIII-XbaI fragment of this gene was cloned into the pcDNA I NEO vector and stably transfected into eukaryotic cells (NIH-3T3). To determine the specific 5-HT1A receptor binding, [3H]8-OH-DPAT was used as radioligand. The selective 5-HT1A receptor agonist bound only a single class of saturable high-affinity binding sites with pharmacological characteristics similar to those of the mammalian 5-HT1A receptor. The effects of X5-HT1A receptor activation on cell growth were also investigated in stably transfected NIH-3T3 cells. The 5-HT1A agonist 8-OH-DPAT was found to increase DNA synthesis and accelerated cell growth.


Photochemical reactions on aerosols at West Antarctica: A molecular case-study of nitrate formation among sea salt aerosols.
Environmental implications of climate change are complex and exhibit regional variations both within and between the polar regions. The increase of solar UV radiation flux over Antarctica due to stratospheric ozone depletion creates the optimal conditions for photochemical reactions on the snow. Modeling, laboratory, and indirect field studies suggest that snowpack process release gases to the atmosphere that can react on sea salt particles in remote regions such as Antarctica, modifying aerosol composition and physical properties of aerosols. Here, we present evidence of photochemical processing in West Antarctica aerosols using microscopic and chemical speciation of individual atmospheric particles. Individual aerosol particles collected at the Brazilian module Criosfera 1 were analyzed by scanning transmission X-ray microscopy with near edge X-ray absorption fine structure spectroscopy (STXM/NEXAFS) combined with computer-controlled scanning electron microscopy (CCSEM) with energy-dispersive X-ray (EDX) microanalysis. The displacement of chlorine relative to sodium was observed over most of the sea salt particles. Particles with a chemical composition consistent with NaCl-NO3 contributed up to 30% of atmospheric particles investigated. Overall, this study provides evidence that the snowpack and particulate nitrate photolysis should be considered in dynamic partition equilibrium in the troposphere. These findings may assist in reducing modeling uncertainties and present new insights into the aerosol chemical composition in the polar environment.


Inflammatory responses of bovine endometrial epithelial cells are increased under in vitro heat stress conditions.
Cattle exposed to heat stress have reduced fertility, reduced milk production and increased incidence of postpartum uterine infection. Heat stress is suggested to alter immune function of cattle; however, the mechanisms underlying heat stress mediated uterine infection are unknown. We hypothesized that exposure of endometrial cells to heat stress would further increase expression of inflammatory mediators in response to bacterial components due to altered heat-shock protein expression. Bovine endometrial epithelial cells (BEND) were exposed to Escherichia coli lipopolysaccharide (LPS) or a synthetic triacylated lipopeptide (Pam3CSK4) under heat stress (41.0 °C) or thermoneutral (38.5 °C) conditions for 24 h. Exposure of BEND cells to LPS or Pam3CSK4 increased the expression of the proinflammatory mediators IL1B, IL6, and CXCL8 compared to control medium. However, exposure of BEND cells to heat stress increased LPS and Pam3CSK4 induced expression of IL1B compared to cells exposed to thermoneutral conditions, and expression of LPS induced IL6 was also increased when BEND cells were exposed to heat stress. To determine if heat shock proteins increased BEND cell expression of inflammatory mediators, HSP1A1 and HSF1 were targeted by siRNA knock down. Expression of HSP1A1 and HSF1 were reduced following siRNA knockdown; however, knockdown of HSP1A1 or HSF1 further increased heat stress mediated increased expression of inflammatory mediators. These data suggest that heat stress increased BEND cell inflammatory responses to bacterial components, while heat shock proteins HSP1A1 and HSF1 help to restrain inflammatory responses. These mechanisms may contribute to the increased incidence of uterine infection observed in cows under heat stress conditions.


COVID-19-associated necrotizing encephalopathy presenting without active respiratory symptoms: a case report with histopathology.
Acute necrotizing encephalopathy (ANE) is a rare complication of coronavirus disease 2019 (COVID-19) secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The condition is typically diagnosed based on characteristic neuroimaging findings in the context of active viral respiratory symptoms. We present a rare case of COVID-19-associated ANE presenting with expressive aphasia and encephalopathy in the absence of active respiratory symptoms. Initial evaluation revealed bilateral thalamic lesions and a mild neutrophilic-predominant pleocytosis on cerebrospinal fluid analysis, the latter of which has not been described in previously published cases. Presence of these atypical features prompted extensive diagnostic evaluation. Metagenomic next-generation sequencing on cerebrospinal fluid did not detect the presence of pathogenic nucleic acids. Thalamic biopsy revealed perivascular neutrophilic inflammation suggestive of small vessel vasculitis with surrounding hemorrhage and necrosis. Ultimately, the diagnosis was made following detection of SARS-CoV-2 serologies and after exclusion of alternative etiologies. The patient was successfully treated with a short course of high-dose methylprednisolone with favorable outcome.


Encapsulation efficiency and fatty acid analysis of chia seed oil microencapsulated by freeze-drying using combinations of wall material.
Chia seed oil (CSO) was encapsulated using whey protein concentrate (WPC) and modified tapioca starch (MTS) through freeze-drying. A central composite design was used to evaluate the effect of independent variables (MTS:WPC ratio, homogenization pressure, and oil content). Encapsulation efficiency (EE) and α-linolenic acid content (ALA) were evaluated for all runs. The results showed that higher MTS ratios led to maximum ALA retention, while higher WPC ratios led to maximum EE. The optimized conditions resulted in high EE (97 %), ALA content (59.54 %), and a Ω-3:Ω-6 ratio (3.34). The fatty acid composition, oxidative and thermal stability showed that the MTS:WPC ratio of 25:75 was the best combination for encapsulating CSO. The encapsulated CSO with a balanced Ω-3:Ω-6 ratio can be used as a functional ingredient in foods for health benefits.


Characterization of fluid flow using low-spatial-resolution velocity spectra from NMR images.
Flow velocity distributions or spectra may be obtained by NMR imaging using an anisotropic three-dimensional Fourier transform pulse sequence in which the low-resolution direction encodes perpendicular velocity. Velocity spectra from regions of interest covering the entire lumens of pipes in a flow phantom containing straight sections, a jet, and a constriction suggest that velocity spectra provide useful information even when the vessels are not spatially well-resolved. The flow in the phantom was characterized and limited measurements were made.


Monoclonal antibodies against carbohydrate differentiation antigens identify subsets of primary sensory neurones.
Dorsal root ganglion (DRG) neurones transmit cutaneous sensory information from the periphery to the spinal cord. Within the dorsal horn of the spinal cord, classes of sensory fibres that are activated by different cutaneous stimuli terminate in separate and highly restricted laminae. Although the developmental events resulting in the laminar organization of sensory afferent terminals have not been defined, it is likely that interactions between surface molecules on DRG and dorsal horn neurones are involved in the generation of afferent synaptic connections. The identification of surface antigens that distinguish functional subclasses of DRG neurones would represent a first step in establishing the existence and nature of such molecules. We report here that monoclonal antibodies directed against carbohydrate differentiation antigens identify cytoplasmic and cell surface molecules expressed selectively by functional subsets of DRG neurons.


[Keratoglobus].
Keratoglobus is a bilateral corneal disease characterised by thinning and protrusion of the entire corneal surface. The cornea is of normal size and usually transparent. Acute corneal edema due to rupture of Descemet's membrane and perforation even from minimal trauma are the most frequent complications. Keratoglobus may be associated with blue sclera, hyperextensibility of the joints or auditory problems. Most often it is a congenital disease with autosomal recessive transmission, but it may be secondarily acquired to an advanced keratopathy (keratoconus), to trauma or to exophthalmos. We report 5 cases of keratoglobus. 4 patients underwent penetrating keratoplasty. The anatomical abnormalities of congenital keratoglobus (3 cases) are constants : an absent Bowman's membrane, a disorganized stroma containing granular material, a thickened, striated Descemet's membrane with breaks, folds and verrucosities. On the other hand, acquired keratoglobus (1 case) shows localised breaks in Bowman's membrane resembling those of keratoconus. The anatomopathological differences are discussed.


[Heat exchange of the rat in thermoneutral zone temperature and comparison with heat exchange in ambient temperature over and under it].
With the help of thermonetry and general calorimetry body temperature and heat production in ambient temperatures 20 degrees C, 28 degrees C, 33 degrees C were recorded. The experiments showed, that at the temperature 20 degrees C the rectal temperature was changing very little. But in ambient temperature 33 degrees C the rectal temperature was 40.5 +/- 0.1 degrees C.


Soluble TNFα-receptor 1 as a predictor of coronary calcifications in patients after long-term cure of Cushing's syndrome.
Increased cardiovascular (CV) risk persists in Cushing's syndrome (CS), despite remission of hypercortisolism. The aim of this study was to evaluate prevalence of coronary artery disease in CS patients and its correlation with classical CV risk factors and inflammatory markers. Cardiac multidetector computed tomography (MDCT) was performed in 41 patients (7 men, 31 of pituitary origin, 29 cured, mean age: 48.6 ± 13 years), using 64-slice Toshiba Aquilion systems. Coronary atherosclerotic plaques were detected and coronary calcifications quantified by the Agatston score (AS). Clinical and biochemical parameters were correlated with the AS to identify possible surrogate markers of coronary disease. Normal values for clinical and biochemical parameters were obtained from a gender- and age-matched normal reference population (n = 82). CS patients with calcifications (AS > 0) (N = 13, 32%) had higher levels of sTNF-R1, homocysteine, triglycerides, blood pressure and body mass index than patients without calcifications (AS = 0) and those of normal reference population. Both groups of CS patients (AS > 0 and AS = 0) had elevated trunk fat mass and IL-6 compared to reference values. Patients with AS > 0 had less adiponectin and higher insulin, HOMA and fibrinogen than those found in normal reference population. sTNF-R1 correlated positively with AS and remained significant after adjusting for confounding factors. The same result was observed when we considered only cured CS patients. In our cohort of CS patients sTNF-R1 was a predictor of coronary calcifications. Since MDCT is an expensive technique not readily available in daily clinical practice, increased sTNF-R1 could be a marker of CV risk even in cured CS.


Postprandial increase of cardiac output in patients with acute myocardial infarction.
The influence on the hemodynamics of oral and intravenous nourishment containing the same amount of calories in comparison to isotonic solution of sodium chloride was studied in 14 patients with acute myocardial infarction. Forty minutes after administration of nourishment, a 34% increase in cardiac index, rising from 2.61 +/- 0.43 to 3.49 +/- 0.68 l/min/m2 was measured in the oral group, P less than 0.001. The increase was 22% (from 2.75 +/- 0.54 to 3.36 +/- 0.83 l/min/m2) in the intravenous group, P less than 0.025. Stroke index rose by 26% (from 33.4 +/- 7.8 to 42.1 +/- 10.6 ml/m2) in the oral group, P less than 0.025; and by 13% (from 32.7 +/- 8.3 to 37.0 +/- 9.7 ml/m2) in the intravenous group, P less than 0.05. No increases were seen in heart rate, mean blood pressure and pulmonary arterial diastolic pressure. The systemic vascular resistance decreased significantly in both groups. Thus, changes that mimic those seen during treatment with positive inotropic or vasodilating drugs were found. These effects have to be taken into account when assessing hemodynamic changes following cardiovascular medication.


The determination of electrical parameters of quartz crystal resonators with the consideration of dissipation.
Recently, as the dissipation of quartz crystal through material viscosity is being considered in vibrations of piezoelectric plates, we have the opportunity to obtain electrical parameters from vibration solutions of a crystal plate representing an ideal resonator. Since the solutions are readily available with complex elastic constants from Mindlin plate equations for thickness-shear vibrations, the calculation of resistance and other parameters related to both mechanical deformation and electrical potential is straightforward. We start with the first-order Mindlin plate equations of a piezoelectric plate for the thickness-shear vibration analysis of a simple resonator model. The electrical parameters are derived with emphasis on the resistance that is related to the imaginary part of complex elastic constants, or the viscosity. All the electrical parameters are frequency dependent, enabling the study of the frequency behavior of crystal resonators with a direct formulation. Through the full consideration of complications like partial electrodes and supporting structures, we should be able obtain electrical parameters for practical applications in resonator design.


Post-endoscopic retrograde cholangiopancreatography pancreatitis assessed using criteria for acute pancreatitis.
International consensus on the definition and classification of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) has been reached. However, the diagnosis and severity of PEP are often assessed according to the diagnostic criteria and classification for acute pancreatitis (AP). This study determined the incidence, severity, and risk factors of PEP diagnosed according to the diagnostic criteria and classification for AP in a large cohort. This prospective, multicenter, observational cohort study conducted at five high-volume centers included 1932 patients who underwent ERCP-related procedures. The incidence, severity, and risk factors for PEP were evaluated. PEP occurred in 142 patients (7.3%); it was mild in 117 patients (6.0%) and severe in 25 patients (1.3%). According to the Cotton criteria, PEP occurred in 87 patients (4.5%); it was mild in 54 patients (2.8%), moderate in 20 patients (1.0%), and severe in 13 patients (0.7%). In the multivariate analysis, female sex (odds ratio [OR] 2.239; 95% confidence interval [CI] 1.546-3.243), naïve papilla (OR 3.047; 95% CI 1.803-5.150), surgically-altered gastrointestinal anatomy (OR 2.538; 95% CI 1.342-4.802), procedure time after reaching the papilla (OR 1.009; 95% CI 1.001-1.017), pancreatic duct injection (OR 2.396; 95% CI 1.565-3.669), and intraductal ultrasonography (OR 1.641; 95% CI 1.024-2.629) were independent risk factors. According to the diagnostic criteria and classification for AP, the incidence of PEP was higher than that according to the Cotton criteria and the severity of PEP tended to be severe.


Asymmetrical radical formation in D- and L-alanines irradiated with yttrium-90 beta-rays.
Radical formation in 90Y-beta-irradiated D- and L-alanines was studied using ESR. It was observed that the relative radical concentration by beta-irradiation was distinguishably (13.9-21.5%) more in D-alanine than in L-alanine. Discussion was made on the possible mechanisms for the observed results.


Correlation of synovial fluid HMGB-1 levels with radiographic severity of knee osteoarthritis.
This study measured high-mobility group box 1 (HMGB-1) levels in serum and synovial fluid (SF) in patients with primary knee osteoarthritis (OA) and correlated these levels with radiographic disease severity. Seventy-eight OA patients and 30 controls were enrolled in this study. All OA patients were scored according to the Kellgren-Lawrence (KL) grading system. HMGB-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). SF HMGB-1 levels were significantly higher in knee OA patients, compared with controls (P < 0.01). Moreover, SF HMGB-1 levels were positively associated with KL scores (P < 0.01). Multinomial logistic regression demonstrated that the SF HMGB-1 level was an independent factor for radiographic severity of OA (P=0.002); however, serum HMGB-1 levels did not differ significantly between OA patients and controls and did not correlate with KL scores (P > 0.05). These results demonstrate that HMGB-1 levels in SF of knee OA patients are independently associated with radiographic disease severity.


Pretreatment blast-to-lymphocyte ratio as a prognostic marker for CD19/CD3-bispecific T cell-engaging antibodies (blinatumomab) treatment against relapsed or refractory B-precursor acute lymphoblastic leukemia.
Blinatumomab is an immunotherapy drug approved for the treatment of acute lymphoblastic leukemia. Since not all patients respond to blinatumomab, markers are needed to predict the efficacy of blinatumomab in individual patients. We hypothesized that the pre-treatment blast-to-lymphocyte ratio would predict blinatumomab efficacy. To examine this possibility, we conducted a post hoc analysis using data from the TOWER Clinical Trials (NCT02013167). Multivariate analysis showed that, along with the treatment groups, each of the following was independently correlated with superior progression-free survival: salvage-treatment phase, allogeneic stem cell transplantation, and pre-treatment ratio of bone marrow blasts-to-peripheral blood lymphocytes < 25.


Long short-term memory with activation on gradient.
As the number of long short-term memory (LSTM) layers increases, vanishing/exploding gradient problems exacerbate and have a negative impact on the performance of the LSTM. In addition, the ill-conditioned problem occurs in the training process of LSTM and adversely affects its convergence. In this work, a simple and effective method of the gradient activation is applied to the LSTM, while empirical criteria for choosing gradient activation hyperparameters are found. Activating the gradient refers to modifying the gradient with a specific function named the gradient activation function. Moreover, different activation functions and different gradient operations are compared to prove that the gradient activation is effective on LSTM. Furthermore, comparative experiments are conducted, and their results show that the gradient activation alleviates the above problems and accelerates the convergence of the LSTM. The source code is publicly available at https://github.com/LongJin-lab/ACT-In-NLP.


[Tuberculosis aneurysm of descending thoracic aorta treated by covered stent graft : A case report].
Tuberculous aneurysm is a rare but lethal disease. It preferentially affects the aorta. The contamination occurs either secondarily to a tuberculosis site in contact with the aorta or by blood contamination. It presents an increased and unpredictable risk of rupture, hence the interest of urgent diagnostic and therapeutic management. His treatment was long based on surgery, but currently the endovascular approach is increasingly used. The treatment, whatever its type, will always be associated with a medical treatment for tuberculosis. We report the case of a patient with a descending thoracic aortic aneurysm considered tuberculous on the basis of epidemiological, clinical and biological arguments; who was treated by deployment of an endoprosthesis with good clinical and radiological evolution.


Estimation of distribution function in bivariate competing risk models.
We consider lifetime data involving pairs of study individuals with more than one possible cause of failure for each individual. Non-parametric estimation of cause-specific distribution functions is considered under independent censoring. Properties of the estimators are discussed and an illustration of their application is given.


Biologically Active Transition Metal Chelates of Ni(II), Cu(II) and Zn(II) With 2-Aminothiazole-Derived Schiff-bases: Their Synthesis, Characterization and the Role of Anions (NO(3), SO(4), C(2)O(4)and CH(3)CO(2-)) on Their Antibacterial Properties.
Biologically active nickel(ll), copper(ll) and zinc(ll) chelates with thiazole-derived nitro- and chlorosalicylaldehyde Schiff-bases having the same metal ion but different anions, e.g. nitrate, sulfate, oxalate and acetate have been synthesized and characterized on the basis of their physical, spectral and analytical data. In order to evaluate the possible participating role of anions on the antibacterial properties, these ligands and their synthesized metal chelates with various anions have been screened against bacterial species Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus.


The effects of dose and access restrictions on the periodicity of cocaine self-administration in the rat.
Cocaine self-administration in rats was tested under various dose and frequency of access restrictions. In the continuous access condition, groups of rats were given continuous, unlimited access to one of three doses of cocaine (1.5, 0.5, and 0.2 mg/kg/infusion) for a duration of 10 days. In the discrete trials condition, a group of rats were given the opportunity to self-administer a single cocaine infusion (1.5 mg/kg) within a discrete, 10 min access trial. The rats received a continuous series of these trials for a duration of 7-10 days at one of three frequencies (1, 2 or 4 trials/h). Results suggest that when access is restricted to four access trials/h, or to a median dose range (0.5 mg/kg per infusion), rats will self-administer cocaine in a cyclical manner over extended, infradian periodicities without developing outward signs of ill health. This contrasts with previous studies where extended, unlimited access schedules have resulted in toxicity and overdose. It is suggested that dose and frequency of access restrictions may be employed in order to develop new animal models of cocaine self-administration which examine the factors underlying the reinitiation of extended periods of cocaine intake. Such models may be useful in testing interventions with the potential to disrupt cyclical patterns of cocaine self-administration.


Integrated transcriptome and miRNA analysis uncovers molecular regulators of aerial stem-to-rhizome transition in the medical herb Gynostemma pentaphyllum.
Gynostemma pentaphyllum is an important perennial medicinal herb belonging to the family Cucurbitaceae. Aerial stem-to-rhizome transition before entering the winter is an adaptive regenerative strategy in G. pentaphyllum that enables it to survive during winter. However, the molecular regulation of aerial stem-to-rhizome transition is unknown in plants. Here, integrated transcriptome and miRNA analysis was conducted to investigate the regulatory network of stem-to-rhizome transition. Nine transcriptome libraries prepared from stem/rhizome samples collected at three stages of developmental stem-to-rhizome transition were sequenced and a total of 5428 differentially expressed genes (DEGs) were identified. DEGs associated with gravitropism, cell wall biosynthesis, photoperiod, hormone signaling, and carbohydrate metabolism were found to regulate stem-to-rhizome transition. Nine small RNA libraries were parallelly sequenced, and seven significantly differentially expressed miRNAs (DEMs) were identified, including four known and three novel miRNAs. The seven DEMs targeted 123 mRNAs, and six pairs of miRNA-target showed significantly opposite expression trends. The GpmiR166b-GpECH2 module involved in stem-to-rhizome transition probably promotes cell expansion by IBA-to-IAA conversion, and the GpmiR166e-GpSGT-like module probably protects IAA from degradation, thereby promoting rhizome formation. GpmiR156a was found to be involved in stem-to-rhizome transition by inhibiting the expression of GpSPL13A/GpSPL6, which are believed to negatively regulate vegetative phase transition. GpmiR156a and a novel miRNA Co.47071 co-repressed the expression of growth inhibitor GpRAV-like during stem-to-rhizome transition. These miRNAs and their targets were first reported to be involved in the formation of rhizomes. In this study, the expression patterns of DEGs, DEMs and their targets were further validated by quantitative real-time PCR, supporting the reliability of sequencing data. Our study revealed a comprehensive molecular network regulating the transition of aerial stem to rhizome in G. pentaphyllum. These results broaden our understanding of developmental phase transitions in plants.


Peltier cooling for the reduction of carbon contamination in scanning electron microscopy.
We used a novel Peltier anticontamination device (PAC) to reduce carbon contamination upon electron beam irradiation in scanning electron microscopy through a reduction of hydrocarbon molecules in the specimen chamber. Unlike liquid-nitrogen based cold traps, the PAC operates free of user maintenance and is suitable for lengthy imaging sessions without degradation of the anticontamination performance. Its performance as an alternative cold trap method provides considerable reduction of electron beam-assisted carbon build-up. We compared the thickness of carbon contamination deposited upon prolonged electron beam scans with the PAC system on and off. Topographical structures of the carbon build-up were characterized using atomic force microscopy. We report that under identical beam parameters, thickness of the carbon contamination was reduced by over 79 % for area scans (1.2 × 1.2 µm2), and by two orders of magnitude for stationary point scans when the PAC cooling mode is engaged.


Nucleotide 9-mers characterize the type II diabetic gut metagenome.
Discoveries of new biomarkers for frequently occurring diseases are of special importance in today's medicine. While fully developed type II diabetes (T2D) can be detected easily, the early identification of high risk individuals is an area of interest in T2D, too. Metagenomic analysis of the human bacterial flora has shown subtle changes in diabetic patients, but no specific microbes are known to cause or promote the disease. Moderate changes were also detected in the microbial gene composition of the metagenomes of diabetic patients, but again, no specific gene was found that is present in disease-related and missing in healthy metagenome. However, these fine differences in microbial taxon- and gene composition are difficult to apply as quantitative biomarkers for diagnosing or predicting type II diabetes. In the present work we report some nucleotide 9-mers with significantly differing frequencies in diabetic and healthy intestinal flora. To our knowledge, it is the first time such short DNA fragments have been associated with T2D. The automated, quantitative analysis of the frequencies of short nucleotide sequences seems to be more feasible than accurate phylogenetic and functional analysis, and thus it might be a promising direction of diagnostic research.


Acute type A hepatitis in three patients with chronic HBV infection.
We have studied three patients with chronic HBV infection who had a superimposed bout of type A hepatitis. The patients recovered uneventfully without observing a change in their clinical course afterwards. In one patient we observed transient disappearance of DNA polymerase during type A hepatitis; we have postulated that this is probably related to hepatic necrosis.


Problems of scientific methodology related to placebo control in Qigong studies: A systematic review.
Qigong is widespread in the West and used for preventive care, stress-induced conditions, emotional and vegetative symptoms like migraine and hypertension, as well as for better coordination in the elderly and quality of life enhancement in severe disease such as cancer. Adequate controls for Qigong research are lacking, compromising the level of efficacy evidence. Adequate Qigong placebo control exercises should match clear and standardized criteria. Three computerized databases were assessed in January 2018 (Scopus, Web of Science and MEDLINE on PubMed) using the following keywords or their combinations: (Qigong OR Qi Gong OR Gong Qi OR Chi Kung OR Kung Chi OR Kiko OR Ki Gong OR Ki Kong) AND placebo. In addition, all reference lists were scanned for further relevant articles. Literature was examined for the effects of Qigong as compared to a control intervention. 110 articles were found, 78 of which were excluded after examining the title and abstract, and 16 because they were duplicates. Four more articles were found by searching in the bibliographies of published papers. A total of 20 studies were included in this systematic review. We found that, to the best of our knowledge, no criteria for placebo controls have been published in peer-reviewed journals so far. Placebo controls should be developed by the usage of vegetative functional assessments such as heart rate variability, thermography, and electrophysiological measurements, thus excluding major vegetative effects of the exercise, as well as by the usage of psychometric tests and other quantitative evaluations.


Necrostatin-1, RIP1/RIP3 inhibitor, relieves transforming growth factor β-induced wound-healing process in formation of hypertrophic scars.
Hypertrophic scars (HS) are common pathologic processes emerged during wound-healing process. The receptor-interacting protein kinase (RIP) might participate in keloid formation. This study aimed to investigate Necrostatin-1 (Nec-1), a RIP1/RIP3 inhibitor, in the formation of hypertrophic scar. Human hypertrophic scar fibroblasts (HSF) were extracted from patients with hypertrophic scar. Transforming growth factor-β1 (TGF-β1) was performed to induce wound-healing process including cell proliferation (CCK-8, Flow cytometry, and Western blot), migration (Transwell assay, Western blot), collagen production (Western blot), and extracellular matrix dysfunction (Western blotting and immunofluorescence). Our results reported that Nec-1 inhibited TGF-β1-induced cell proliferation and promoted G0/G1 phase arrest in HSF. In addition, Nec-1 attenuated TGF-β1-induced cell migration and inhibited the expression of MMP2 and MMP9 in TGF-β1-induced HSF. Besides, Nec-1 also reduced TGF-β1-induced collagen production and α-smooth muscle actin expression in HSF. The present data in this study showed the potential role of Nec-1 as a novel treatment for HS.


Pathways of the relationships among eating behavior, stress, and coping in adults with type 2 diabetes: A cross-sectional study.
Stress is related to eating behavior, and eating behavior is important in diabetes treatment. The aim of this study was to examine the relationships among perceived stress, diabetes-related stress, coping strategies, and eating behaviors in adults living with type 2 diabetes (T2DM). Adults with type 2 diabetes (n = 183) were recruited from a large metropolitan area in the Midwest United States. Stress factors and coping strategies associated with eating behaviors were measured using validated questionnaires. Structural equation modeling was used to investigate the relationships among perceived stress, diabetes-related stress, coping strategies, and eating behaviors. The final model showed that emotion-oriented coping partially mediated the effect of stress on eating behaviors. Specifically, emotion-oriented coping partially mediated the effect of diabetes-related stress on restrained eating behavior (r = 0.318, p < .001) and emotional eating behavior (r = 0.399, p < .001); emotion-oriented coping partially mediated the effect of perceived stress on external eating behavior (r = 0.276, p < .001). Emotion-oriented coping was found to be a partial mediator in the path model between stress and eating behaviors in people with type 2 diabetes. Knowledge of the association of stress with eating behaviors may prove important for health care providers in treatment and care of people with type 2 diabetes.


Kisspeptin and LH pulsatility in patients with functional hypothalamic amenorrhea.
Functional hypothalamic amenorrhea (FHA) occurs in response to exaggerated stressors with or without body weight loss. Various hormones, neurotransmitters, and neuromodulators are involved in the control of GnRH and kisspeptin is one of them. Our study aimed to evaluate the putative temporal coupling between kisspeptin and GnRH-induced LH pulsatile secretion. In total, 71 patients with FHA were selected for this study. All patients undergo to a pulsatility study for LH and kisspeptin evaluation (120 min, sampling every 10 min), and to an endocrine evaluation for prolactin (PRL), estradiol (E2), androstenedione (A), 17-hydroxy-progesterone (17OHP), TSH, fT3, fT4, insulin, cortisol and testosterone (T), glucose, total cholesterol, triglycerides. Our data demonstrated kisspeptin and LH pulsatile secretions and that both hormones are co-secreted and temporally coupled at time 0 (p < 0.05). When patients were subdivided in hypo-LH (≤3 mIU/ml, n = 58) and normo-LH (>3 mIU/ml, n = 13), more insights were observed on the specific correlations of metabolic and hormone profiles with pulsatility indexes of LH and kisspeptin. Our study demonstrated the presence of a distinct kisspeptin episodic secretion in patients with FHA, and showed the temporally coupling of kisspeptin with LH secretory episodes thus supporting that though in amenorrhea, the reproductive axis is still relying on kisspeptin to drive GnRH discharge. In addition, correlations among hormonal data sustain the hypothesis that stress-induced compensatory events are the main direct and indirect promoters of the reproductive blockade in patients affected by FHA.


Ophthalmic genetic counselling: emerging trends in practice perspectives in Asia.
Genetic counselling (GC) provides information to the patient and the family to make informed choices. Among the advanced Western countries and a few Asian countries, there are certified or trained professionals who perform GC. The Human Genome Project and next-generation sequencing diagnostics have provided an opportunity for increased genetic testing in the field of ophthalmology. The recent interventional therapeutic research strategies have also generated additional interest to seek GC globally, including in Asia. However, GC has several barriers to practise in the developing countries in Asia, namely, (a) shortage of qualified or trained genetic counsellors, (b) poor knowledge and reluctance in clinical adoption of genomics among the physicians in clinical practice, (c) overstretched public health services, and (d) negligible ophthalmic GC-related research and publications. The GC inadequacy in Asia is glaring in the most populous countries like China and India. Cultural differences, religious beliefs, misogyny, genetic discrimination, and a multitude of languages in Asia create unique challenges that counsellors in the West may only encounter with the immigrant minorities. Since there are currently 500 or more specific Mendelian genetic eye disorders, it is important for genetic counsellors to translate the genetic results at a level that the patient and family understand. There is therefore a need for governmental and healthcare organisations to train genetic counsellors in Asia and especially this practice must be included in the routine comprehensive ophthalmic care practice.


Noncontact analysis of the fiber weight per unit area in prepreg by near-infrared spectroscopy.
The fiber weight per unit area in prepreg is an important factor to ensure the quality of the composite products. Near-infrared spectroscopy (NIRS) technology together with a noncontact reflectance sources has been applied for quality analysis of the fiber weight per unit area. The range of the unit area fiber weight was 13.39-14.14mgcm(-2). The regression method was employed by partial least squares (PLS) and principal components regression (PCR). The calibration model was developed by 55 samples to determine the fiber weight per unit area in prepreg. The determination coefficient (R(2)), root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) were 0.82, 0.092, 0.099, respectively. The predicted values of the fiber weight per unit area in prepreg measured by NIRS technology were comparable to the values obtained by the reference method. For this technology, the noncontact reflectance sources focused directly on the sample with neither previous treatment nor manipulation. The results of the paired t-test revealed that there was no significant difference between the NIR method and the reference method. Besides, the prepreg could be analyzed one time within 20s without sample destruction.


Central venous thrombosis in children with intestinal failure on long-term parenteral nutrition.
Central venous thrombosis (CVT) is a serious complication of long-term central venous access for parenteral nutrition (PN) in children with intestinal failure (IF). We reviewed thse incidence of CVT and possible risk factors. Children with IF on home PN (2010-2014) with central venous imaging were reviewed. Patient demographics, catheter characteristics and related complications, and markers of liver function were compared between children with and without CVT. Serum thrombophilia markers were reviewed for patients with CVT. Thirty children with central venous imaging were included. Seventeen patients had thrombosis of ≥1 central vein, and twelve had ≥2 thrombosed central veins. Patients with and without CVT had similar demographics and catheter characteristics. Patients with CVT had a significantly lower albumin level (2.76±0.38g/dL vs. 3.12±0.41g/dL, p=0.0223). The most common markers of thrombophilia in children with CVT were antithrombin, protein C and S deficiencies, and elevated factor VIII. There was a statistically significant correlation between a combined protein C and S deficiency and having >1 CVT. Children with IF on long-term PN are at high risk for CVT potentially owing to low levels of natural anticoagulant proteins and elevated factor FVIII activity, likely a reflection of liver insufficiency and chronic inflammation.


α-Synuclein in blood cells differentiates Parkinson's disease from healthy controls.
To determine whether blood cells expressed α-Syn can differentiate Parkinson's disease (PD) from healthy controls (HC). The concentrations of α-Syn were determined in samples of blood cell pellets using a quantitative Lipid-ELISA assay. In addition, the levels of total protein, hemoglobin, iron and H-ferritin were determined. The study includes samples from the Biofind cohort (n = 46 PD and 45 HC) and results were validated with an additional cohort (n = 35 PD and 28 HC). A composite biomarker consisting of the concentrations of total α-Syn, proteinase-K resistant (PKres ) α-Syn and phospho-Serine 129 α-Syn (PSer 129), is designed based on the analysis of the discovery BioFIND cohort. This composite biomarker differentiates a PD subgroup, presenting motor symptoms without dementia from a HC group, with a convincing accuracy, represented by an AUC = 0.81 (95% CI, 0.71 to 0.92). Closely similar results were obtained for the validation cohort, that is, AUC = 0.81, (95% CI, 0.70 to 0.94). Our results demonstrate the potential usefulness of blood cells expressed α-Syn as a biomarker for PD.


The science of cognitive therapy.
Cognitive therapy (CT) refers to a family of interventions and a general scientific approach to psychological disorders. This family has evolved from a specific treatment model into a scientific approach that incorporates a wide variety of disorder-specific interventions and treatment techniques. The goal of this article is to describe the scientific approach of CT, review the efficacy and validity of the CT model, and exemplify important differences and commonalities of the CT approaches based on two specific disorders, posttraumatic stress disorder and health anxiety.


The spectrum of polymyalgia rheumatica.
Polymyalgia rheumatica and temporal arteritis are common syndromes of unknown cause that afflict older patients, the great majority of whom are white. Polymyalgia, which is seen more frequently, is a benign synovitis and can be differentiated from rheumatoid arthritis by the distribution of inflamed joints and by its rapid and complete response to small doses of prednisone. Temporal or giant cell arteritis occurs in approximately 20 per cent of patients with polymyalgia rheumatica and may present with either localized or systemic symptoms. Once the diagnosis is confirmed by temporal artery biopsy, patients should be treated with a large dose of prednisone for at least 1 month. The erythrocyte sedimentation rate is a useful test in suspecting the diagnosis initially, but is a poor gauge to tapering the steroid dose.


Calcite saturation in eastern UK rivers.
Calcite saturation in eastern UK rivers is assessed in relation to the potential kinetic inhibition of calcite precipitation. Two well established inhibitors are considered: soluble reactive phosphorus (SRP, i.e. inorganic monomeric phosphorus); and dissolved organic carbon (DOC). The rivers show a range of calcite saturation levels from approximately 1hundredth to approximately 100-fold. The greatest range occurs for the northernmost river considered, the Tweed, where the waters range from highly unsaturated to highly oversaturated. The lowest range occurs for the most southerly rivers (the Great Ouse and the Thames) where the waters are consistently oversaturated with respect to calcite. The contrasting patterns relate to a greater diversity of water quality within the northern regions. Thus, during the winter, the main waters are derived from the upland areas with acidic soils and low weathering rates. During the summer baseflow periods, groundwater inputs are more important and high photosynthesis results in particularly high pHs and calcite oversaturation. In contrast, for the southern rivers, the main source of water during both the summer baseflow and the winter highflow periods comes from calcium carbonate rich aquifer sources. Statistical analysis of pH vs. the logarithm of the calcite saturation index for each river indicates strong linear features with individual gradients of approximately 1. This linearity results from an autocorrelation (the logarithm of the saturation index is calculated from the pH) and this indicates that calcite solubility controls are not operative in any of the rivers examined. A comparison of calcite saturation levels and SRP and DOC concentrations show a pattern inconsistent with kinetic hindrance, although some structure is observed, probably due to the mixing reactions between point and diffuse sources of water with contrasting chemistry.


Post intensive care syndrome in survivors of COVID-19 who required mechanical ventilation during the third wave of the pandemic: A prospective study.
Post intensive care syndrome is defined as the presence of any impairment affecting the physical, psychiatric, or cognitive domains as a result of critical illnesses. To explore functional, cognitive and psychological outcomes at 30 days post hospital discharge among survivors of COVID-19-associated acute respiratory distress syndrome, who required mechanical ventilation. Prospective cohort study. We included adult patients with COVID-19-associated acute respiratory distress syndrome, invasively ventilated in two ICUs in Buenos Aires. We measured functional, cognitive and psychological impairments with Barthel index, Montreal Cognitive Assessment test, Patient Health Questionnaire-9 and General Anxiety Disorder-7. Primary outcome was post-intensive care syndrome. Secondary outcome was mortality at 60 days. We admitted 40 patients, median age was 69 (60-75) and mostly male (75%). Mortality at 60 days was 37%. Cox regression analysis identified diabetes and Apache II as independent predictors of mortality. Out of 22 patients studied, 14 (64%) developed PICS after discharge. With a physical, cognitive and psychological impairment in 64%, 41% and 32% of patients, respectively. Obesity, days of mechanical ventilation, Apache II, vasopressors use, delirium duration and cumulative midazolam dose were associated with functional dependence. We identified a high prevalence of functional, cognitive and mental impairment at 30 days after hospital discharge in COVID-19-associated acute respiratory distress syndrome survivors, invasively ventilated. The physical domain was the most frequently affected. These findings suggest the need for long-term follow-up of this population.


The scope for regulatory incentives to encourage increased efficiency of input use by farmers.
Managing diffuse water pollution from agricultural land continues to be one of the more intractable challenges for environmental policy. The advent of the Water Framework Directive places the onus on EU member states to identify reasons why water bodies fail or are at risk of failure to meet good ecological status. In such cases, programmes of measures are to be enacted to mitigate the causes at least cost. Failing this, users may ultimately be faced with the full costs of pollution. This paper considers the scope for measures that address nitrogen and phosphorus pollution at source. Specifically the paper relates the diffuse pollution problem to the extent of over application of nitrogen and phosphorus. Data envelopment analysis applied to English cereal and dairy farmers, provides an indication of resource use and evidence of over application. This inefficiency provides a potential basis for either a least cost abatement approach using effective information and advice, or alternatively a pollution charge.


Inductions of histone H3 acetylation at lysine 9 on SGLT1 gene and its expression by feeding mice a high carbohydrate/fat ratio diet.
We examined in this study whether histone H3 acetylations on jejunal NA(+)/glucose transport-1 (SGLT1) gene are associated with induction of its gene by feeding mice a high carbohydrate/fat ratio diet. The chromatin immunoprecipitation (ChIP) assays using antibodies of acetylated histone H3 were performed in jejunum of mice fed a high carbohydrate/fat ratio diet or a low carbohydrate/fat ratio for 7 d. The acetylations of histone H3 of lysine 9/14 were highly detected on the SGLT1 gene and the levels were enhanced by feeding mice a high carbohydrate/fat ratio diet. Histone H3 acetylation at lysine 9 was enhanced by feeding a high carbohydrate/fat ratio diet, whereas that at lysine 14 was not enhanced significantly. These observations indicate that induction of SGLT1 gene expression by feeding a high carbohydrate/fat ratio diet is associated with acetylation of histone H3 at lysine 9 on the SGLT1 gene.


WT1 mutation in pediatric patients with acute myeloid leukemia: a report from the Japanese Childhood AML Cooperative Study Group.
Mutations in Wilms tumor 1 (WT1) have been reported in 10-22 % of patients with cytogenetically normal acute myeloid leukemia (CN-AML), but the prognostic implications of these abnormalities have not been clarified in either adults or children. One hundred and fifty-seven pediatric AML patients were analyzed for WT1 mutations around hotspots at exons 7 and 9; however, amplification of the WT1 gene by the reverse transcriptase-polymerase chain reaction was not completed in four cases (2.5 %). Of the 153 evaluable patients, 10 patients (6.5 %) had a mutation in WT1. The incidence of WT1 mutations was significantly higher in CN-AML than in others (15.2 vs. 4.5 %, respectively, P = 0.03). Of the 10 WT1-mutated cases, eight (80 %) had mutations in other genes, including FLT3-ITD in two cases, FLT3-D835 mutation in two, KIT mutation in three, MLL-PTD in three, NRAS mutation in one, and KRAS mutation in two (in some cases, more than one additional gene was mutated). The incidences of KIT and FLT3-D835 mutations were significantly higher in patients with than in those without WT1 mutation. No significant differences were observed in the 3-year overall survival and disease-free survival; however, the presence of WT1 mutation was related to a poor prognosis in patients with CN-AML, excluding those with FLT3-ITD and those younger than 3 years.


Retracted: Application of Sandplay Therapy in the Mental Health Education of Vocational College Students.
[This retracts the article DOI: 10.1155/2022/6141326.].