In situ synthesis of lipopeptides as versatile receptors for the specific binding of nanoparticles and liposomes to solid-supported membranes.
A detailed study of the in situ coupling of small peptides such as CGGH6 (H6) and CGWK8 (K8) to maleimide functionalized phospholipid bilayers is presented. Individually addressable microstructured membranes are employed to unequivocally probe the conjugation. The in situ coupling of peptides via a terminal cysteine moiety to maleimide functionalized phospholipids is shown to be a convenient and versatile way to selectively fabricate peptide-modified phospholipid bilayers serving as specific receptor platforms for functionalized vesicles and nanoparticles. Specific binding of functional vesicles to the peptide-modified bilayers is achieved by either histidine complexation with Ni-NTA-DOGS containing vesicles or electrostatic interaction between positively charged oligolysine bearing lipopeptides and negatively charged POPC/POPG vesicles. Peptide receptors are also found to be easily accessible from the aqueous phase and not buried within the membrane interior.


A pairwise interaction model for multivariate functional and longitudinal data.
Functional data vectors consisting of samples of multivariate data where each component is a random function are encountered increasingly often but have not yet been comprehensively investigated. We introduce a simple pairwise interaction model that leads to an interpretable and straightforward decomposition of multivariate functional data and of their variation into component-specific processes and pairwise interaction processes. The latter quantify the degree of pairwise interactions between the components of the functional data vectors, while the component-specific processes reflect the functional variation of a particular functional vector component that cannot be explained by the other components. Thus the proposed model provides an extension of the usual notion of a covariance or correlation matrix for multivariate vector data to functional data vectors and generates an interpretable functional interaction map. The decomposition provided by the model can also serve as a basis for subsequent analysis, such as study of the network structure of functional data vectors. The decomposition of the total variance into componentwise and interaction contributions can be quantified by an [Formula: see text]-like decomposition. We provide consistency results for the proposed methods and illustrate the model by applying it to sparsely sampled longitudinal data from the Baltimore Longitudinal Study of Aging, examining the relationships between body mass index and blood fats.


[Reliability of the transcutaneous PO2 measurement in the adult by the TCM 1 radiometer electrode].
The accuracy of transcutaneous PO2 measurements (PtcO2; Radiometer TCM 1) was evaluated by comparison with arterial PO2 (PaO2) on 115 recordings in 35 patients: 20 during exercise testing (group I) and 14 during assisted ventilation at different FIO2 values (group II). The correlation coefficient between PaO2 and PtcO2 was satisfactory (r = 0.977; n = 115). However PaO2 and PtcO2 mean values were significantly different in group I, and in group II at 45% FIO2. The analysis of variance showed that the difference between PaO2 and PtcO2 was significant among the patients but did not vary with exercise and FIO2 changes (group I: F19 = 6.28, p less than 0.001; group II: F19(19) = 2.54, p less than 0.025). In the adult, transcutaneous PO2 measurement by TCM 1 radiometer electrode seems to be interesting in the context of monitoring blood gases with exercise and assisted ventilation. The significant variation with arterial PO2 sometimes registered should make one cautious in the interpretation of accurate measurements.


Human dura mater as a wrapping material for hydroxyapatite implantation in the anophthalmic socket.
Homologous sclera and autologous fascia lata have been accepted as common wrapping materials for hydroxyapatite implantation; however, various problems have been observed, such as the risk of transmittable diseases such as AIDS or hepatitis. This report details the use of cadaver dura mater to wrap hydroxyapatite implants. For 73 eyes of 73 patients with hydroxyapatite implantation, cadaver dura mater was used to wrap the hydroxyapatite after enucleation or secondary implantation. Of the 73 patients, 20 had conjunctival erosion; however, all of the patients but 1 healed spontaneously within an average of 22 days. Only 1 of the 73 patients progressed to implant exposure requiring a dermis graft. The authors suggest that cadaver dura mater is a suitable wrapping material for hydroxyapatite implantation.


A retrospective cohort study of prescribing outcomes in outpatients treated with nirmatrelvir-Ritonavir for COVID-19 in an interdisciplinary community clinic.
Large observational studies have demonstrated the real-world effectiveness of nirmatrelvir-ritonavir in preventing severe COVID-19 in higher risk individuals, but have provided limited information on other aspects of nirmatrelvir-ritonavir use. Our objective was to evaluate prescribing outcomes such as the prevalence of drug-drug interactions (DDI), adverse drug events (ADE) and treatment adherence in an outpatient community clinic setting. We conducted a single-centre retrospective cohort study of adult outpatients prescribed nirmatrelvir-ritonavir in our community COVID-19 assessment clinic in Toronto, Ontario between March 3 and September 20, 2022. We performed a descriptive analysis of the patient population, DDIs, DDI interventions, treatment adherence, ADEs and clinical outcomes of patients prescribed nirmatrelvir-ritonavir. There were 637 individuals prescribed nirmatrelvir-ritonavir during the study period. The median age was 70, the median number of risk factors for severe disease were 2, 45% were immunocompromised and 82% had received 3 or more COVID-19 vaccine doses. 95% (542/572) completed the 5-day course of therapy with 68% (388/572) having complete symptom resolution by 28-day. Eleven percent (60/572) experienced recurrent symptoms following the completion of nirmatrelvir-ritonavir. Over 70% had one or more clinically significant DDIs requiring mitigation and 62% of patients experienced at least one ADE, which was most commonly dysgeusia or gastrointestinal-related. Ninety-five percent (542/572) of patients completed therapy as prescribed. Overall, hospitalization within 28 days was 3.3% with 1.2% attributed to COVID-19 and there were no deaths. Nirmatrelvir-ritonavir was associated with a high prevalence of clinically significant DDIs, which required mitigation strategies and a high frequency of mild ADEs. Collaborative assessment to address medication alterations resulted in high treatment adherence.


Hypoxic storage of erythrocytes slows down storage lesions and prolongs shelf-life.
Conventional storage conditions of erythrocytes cause storage lesions. We propose that hypoxic storage conditions, involving removal of oxygen and replacement with helium, the changes in stored erythrocytes under hypoxic condition were observed and assessed. Erythrocytes were divided into two equal parts, then stored in conventional and hypoxic conditions, separately. Blood gas analysis, hemorheology, and hemolysis were performed once a week. Energy metabolism and membrane damage were monitored by enzyme-linked immunosorbent assay. Phosphatidylserine exposure was measured by flow cytometry. P50 was measured and the oxygen dissociation curve (ODC) plotted accordingly. Erythrocyte morphology was observed microscopically. In the 9th week of storage, the hemolysis of the hypoxia group was 0.7%; lower (p < .05) than that of the control group and still below the threshold of quality requirements. The dissolved oxygen and pO2 were only 1/4 of that in the control group (p < .01); the adenosine triphosphate, glucose, and lactic acid levels were decreased (p < .05), while the 2,3-diphosphoglycerate levels were increased relative to that in the control group (p < .01). There were no statistically significant differences in membrane damage, deformability, and aggregation between the two groups. In addition, the ODC of the two groups was shifted to the left but this difference was not statistically different. Basically similar to the effect of completely anaerobic conditions. Erythrocytes stored under hypoxic conditions could maintain a relatively stable state with a significant decrease in hemolysis, reduction of storage lesions, and an increase in shelf-life.


The Association of Thyroid Hormone Changes with Inflammatory Status and Prognosis in COVID-19.
COVID-19 infection may have multiorgan effects in addition to effects on the lungs and immune system. Recently, studies have found thyroid function abnormalities in COVID-19 cases which were interpreted as euthyroid sick syndrome (ESS) or destructive thyroiditis. Therefore, in this study, we aimed to evaluate the thyroid function status and thyroid autoimmunity in COVID-19 patients. Material and Method. 205 patients were included. The medical history and laboratory parameters at admission were collected from medical records. Serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody, and thyroglobulin antibody were measured, and patients were classified according to thyroid function status. 34.1% of the patients were euthyroid. Length of hospitalization (p < 0.001), rate of oxygen demand (p < 0.001), and intensive care unit (ICU) admission (p=0.022) were lower, and none of the euthyroid patients died. 108 (52.6%) patients were classified to have ESS, 57 were classified as mild, and 51 were moderate. The inflammatory parameters were higher in patients with moderate ESS. In cluster analysis, a high-risk group with a lower median FT3 value (median = 2.34 ng/L; IQR = 0.86), a higher median FT4 value (median = 1.04 ng/dL; IQR = 0.33), and a lower median TSH value (median = 0.62 mIU/L; IQR = 0.59) included 8 of 9 died patients and 25 of the 31 patients that were admitted to ICU. Discussion. Length of hospitalization, oxygen demand, ICU admission, and mortality were lower in euthyroid patients. Moreover, none of the euthyroid patients died. In conclusion, evaluation of thyroid function tests during COVID-19 infection may give information about the prognosis of disease.


Low-intensity shockwave therapy for erectile dysfunction: is the evidence strong enough?
Erectile dysfunction (ED) affects ∼30% of all men above the age of 40 years and its prevalence steadily increases with age. Current nonsurgical treatment options, including phosphodiesterase type 5 inhibitors (PDE5I), provide temporary relief but have failed to provide a permanent improvement of the condition. Low-intensity extracorporeal shockwave therapy (Li-ESWT) is noninvasive and uses acoustic waves, which can pass through tissue and be focussed to target specific areas or organs to induce the desired effects. The use of Li-ESWT has previously been described in other disease contexts, such as ischaemic heart disease, bone fractures, and burns, in which it improves neoangiogenesis; similar principles seem to apply in the erectile tissue. The major potential advantage of the treatment, therefore, is the possibility to restore natural erectile function. Thus, Li-ESWT is the only currently marketed treatment for ED that might offer a cure, which is the most desired outcome for most men with ED. Li-ESWT has also been suggested to improve the effect of PDE5I in nonresponders, reducing the need for more invasive treatments. Several single-arm trials have shown benefit of Li-ESWT on patient-reported erectile function scores, but data from randomized trials are conflicting, and many questions remain to be answered before we can routinely offer this treatment to patients. Thus, the search for the true clinical value of Li-ESWT for ED represents a dynamic and continuing field of enquiry.


Anti-apoprotein B monoclonal antibodies detect human low density lipoprotein polymorphism.
Immunochemical polymorphism among human low density lipoproteins (LDL) isolated from different individuals was demonstrated through reduced binding of three monoclonal antibodies to some individual LDL using a solid phase radioimmunoassay. These three antibodies are members of a larger group of monoclonal antibodies previously shown to bind specifically to apoprotein B ( Curtiss , L.K., and Edgington , T. S. (1982) J. Biol. Chem. 257, 15213-15221; Tsao , B.P., Curtiss , L. K., and Edgington , T.S. (1982) J. Biol. Chem. 257, 15222-15228). Those antibodies which distinguished human LDL polymorphism bound to the same or adjacent epitopes on LDL, for they were mutually exclusive in competitive binding experiments. Binding was unaffected by treatment with neuraminidase, with a mixture of glycosidases, or with competing glycoproteins; thus, the carbohydrate moiety of apoprotein B did not appear to influence the epitope recognized by these antibodies. When low density lipoproteins isolated from different individuals were studied, three different phenotypes were recognized; these corresponded to strong, weak, and intermediate binding of the three monoclonal antibodies. This division into three phenotypes is demonstrated to result from a genetic polymorphism; indeed, the data fit a model consisting of two co-dominant apoprotein B alleles, and the three phenotypes then correspond to the two human homozygotes and the heterozygote. The classical Ag antigen phenotype was determined for the LDL isolated from 10 individuals who were also studied with the monoclonal antibodies, and no correspondence was found between the different epitopes recognized by the five presumptive Ag allelic pairs, x/y, a1/d, c/g, t/z, or h/i, and the site recognized by the monoclonal antibodies. All of these data are discussed, and it is concluded that the most likely explanation for the difference in recognition of the two allelic forms of apoprotein B is an alteration in amino acid sequence resulting in a slightly different configuration of a single domain containing the epitopes recognized by the three monoclonal antibodies.


Interleukin-1 beta increases prostaglandin E2 in rat astrocyte cultures: modulatory effect of neuropeptides.
Recombinant human interleukin-1 beta (IL-1 beta) significantly increased prostaglandin E2 (PGE2) in a dose-dependent manner in rat astrocyte culture. The minimum effective dose of IL-1 beta was 10(-10)M. IL-1 alpha also increased PGE2, but at a higher concentration. The minimum effective dose of IL-1 alpha was 10(-8)M, indicating it to be 100-fold less effective than IL-1 beta. On the other hand neither IL-1 beta nor IL-1 alpha increased PGE2 production by neuron cultures at any concentration tested. PGE2 response to IL-1 beta was suppressed by simultaneous addition of CRH, somatostatin-14 and LHRH, while these neuropeptides alone did not alter the basal PGE2 levels. Substance P, vasoactive intestinal polypeptide and alpha-MSH altered neither basal nor IL-1 beta-induced increase in PGE2 levels. Angiotensin II (AII) alone also increased PGE2 in cultured astrocytes. Combined addition of AII and IL-1 beta induced a synergistic effect in increasing PGE2 levels. The direct action of IL-1 beta on astrocyte culture suggests that astrocytes may be the target cells for IL-1 beta in the central nervous system. In view of the essential role of central PGE2 in IL-1 beta-induced CRH/ACTH release, these findings suggest the presence of a sophisticated regulatory network in the immune-neuroendocrine interaction.


Experiments on the role of potassium in the blocking of neuromuscular transmission by curare and other drugs.
1. Experiments with perfused frog muscles and with isolated frog muscles immersed in Ringer's solution have failed to show any effect of curare in liberating potassium from muscle tissue. This makes it difficult to suppose that the paralytic effect of curare can be attributed to cation exchange between curare and K whereby a labile potassium compound needed for stimulation is removed from the neuromuscular junction. 2. Similar negative results were obtained with dihydro-beta-erythroidine and myanesin. 3. A small liberation of K from perfused muscle does result from treatment with acetylcholine. This is probably due to the contracture of the muscle since the effect is largely eliminated by previous treatment of the muscle with curare. The amount of potassium lost in this way from perfused muscles is too small to detect when muscles are analyzed after immersion in Ringer's solution with and without acetylcholine. It is concluded that there is no significant cation exchange between acetylcholine and K in muscle, but only a small loss of K due to the contracture produced by the acetylcholine.


Spinal cord injury and serum erythropoietin.
The origin of the temporary reduction in hematocrit and hemoglobin occurring after spinal cord injury (SCI) may be related to the neurologic dysfunction and to a change in erythropoietin (Ep) synthesis and/or secretion. Serum Ep, vital capacities, and numerous hematologic profiles were obtained in 12 cervical SCI patients during the first 12 weeks and 13th to 27th post-injury weeks, and in 8 thoracic SCI patients during the first 8 weeks and 9th to 28th weeks. Serum iron, iron binding, and saturation were obtained in 4 cervical SIC patients and blood gases in 10 patients with cervical SCI and in 6 with thoracic SCI. The results in all patients showed increased Ep values, returning to normal after 8 weeks in the thoracic SCI patients only. The few results on iron kinetics showed a tendency to low values, suggesting the necessity for further investigation. In an attempt to explain the Ep increase in SCI patients, the relative influence of the renal pelvic nerves and of the sympathetic nerves on its secretion, are examined.


[Prosthetic hip revision: relationship between bone stock and quality of life in aseptic loosening of the femoral component].
We evaluated the clinical and radiographic results in the medium and long term in patients undergoing revision surgery for aseptic loosening with different bone quality at the time of the operation. We investigated how different bone quality shapes for a good clinical result. A total of 33 patients who underwent revision surgery of the hip (for aseptic loosening of the stem) evaluated radiographically and clinically at 1,6,12 and 18 months. The evaluation of clinical status preoperatively and at the end of follow-up was be made as questionnaires SF-36, Harris Hip Score and WOMAC; radiographic assessment was made using the scale of Paprosky. The data thus obtained have been related to complications arising and the status of femoral bone-loss before the surgery time. The groups PI and PII (Paprosky) showed a high level of satisfaction with an average value of reference for the postoperative rated as excellent, the absence of complications and good functional recovery at the end of follow-up. The groups PIII and PIV showed increased incidence of complications and difficulties with rehabilitation clinics and SF-36 scores and HHS inferior to other classes. Our dates confirm that bone quality at the time of surgery affects the therapeutic target. All patients with good bone quality at the time of the revision surgery (groups PI and PII) showed a distinct advantage from surgical treatment. Revision surgery had not much effect in patients with high bone loss. Preservation of bone stock should be considered a good foundation for the success of a prosthetic reimplantation with better functional and radiographic out-come associated with greater satisfaction for the patient.


Vitamin D deficiency contributes to overtraining syndrome in excessive trained C57BL/6 mice.
Overtraining syndrome is a condition resulting from excessive training load associated with inadequate recovery and poor sleep quality, leading to performance decrements and fatigue. Here we hypothesized that vitamin D (VitD) deficiency is a lead factor in the development of the overtraining syndrome. To test this hypothesis, two groups of 60-week-old C57BL/6 mice followed a 16-week excessive eccentric-based overtraining by excessive downhill running with or without dietary VitD depletion (EX and EX-D- groups). Two control groups were trained by uphill running at the same load with or without VitD depletion (CX and CX-D- groups). Handgrip strength decreased throughout the protocol for all groups but the decrease was sharper in EX-D- group (VitD × training, p = 0.0427). At the end of the protocol, the mass of Triceps brachii muscle, which is heavily stressed by eccentric contractions, was reduced in eccentric-trained groups (training effect, p = 0.0107). This atrophy was associated with a lower concentration of the anabolic myokine IL-15 (training effect, p = 0.0314) and a tendency to a higher expression of the atrogene cathepsin-L (training effect, p = 0.0628). VitD depletion led to a 50% decrease of the fractional protein synthesis rate in this muscle (VitD effect, p = 0.0004) as well as decreased FGF21 (VitD effect, p = 0.0351) and increased osteocrin (VitD effect, p = 0.038) concentrations that would lead to metabolic defects. Moreover, the proportion of anti-inflammatory Th2 lymphocytes was significantly decreased by the combination of eccentric training with VitD depletion (vitD × training, p = 0.0249) suggesting a systemic inflammation. Finally, exploratory behavior time of mice was decreased by VitD depletion (VitD effect, p = 0.0146) suggesting a cognitive dysfunction. Our results suggest that VitD deficiency exacerbates the effects of overtraining.


Integrating qualitative and quantitative data analysis.
Few texts on quantitative research pay any attention to qualitative analysis ( 1 , 2 ). Similarly, few books on qualitative analysis explore the potential of its relationship with quantitative analysis. However, Silverman ( 3 ) has suggested that numbers can provide valuable contextual material for qualitative data.


Children's at Home: Pilot Study Assessing Dedicated Social Media for Parents of Adolescents with Neurofibromatosis Type 1.
The aim of this pilot study was to evaluate Children's at Home (C@H), a dedicated social media website for parents of adolescents with neurofibromatosis type 1 (NF1). The interventional study included two phases: (1) creating video intervention/prevention assessment (VIA) visual narratives about having an adolescent with NF1 and (2) interacting on C@H, a secure, medically moderated social media website. C@H was evaluated qualitatively at three time points. At enrollment (T0, N = 17), participants reported needing C@H to break their isolation, connect with other families, and receive accurate information, advice, and support from others facing similar challenges. At T1, after creating VIA during 6 months (N = 13, 145 videos), participants mostly valued the opportunity to speak about the challenges they face with NF1 and their journey since diagnosis. At T2, after interacting on C@H for 7 weeks (N = 10, two sign-ins/week/parent), participants reported connecting with other parents of children with NF1 for the first time, valuing the "real faces" and emotions of other parents with shared experiences providing a sense of normalcy. Qualitative analysis suggested that C@H decreased feelings of isolation, provided relief to talk about NF1 without having to explain it, provided new knowledge about NF1 and the opportunity to address non-medical issues of NF1 never discussed in clinic, and helped participants with putting their lives into perspective. C@H allowed parents of adolescents with NF1 to overcome previous isolation and connect for the first time. Innovative applications of social media dedicated to those who care for children with chronic conditions can provide peer-to-peer support, shared experience, and reliable medical information.


[Andersson lesion in ankylosing spondylitis: a clinical study of 14 cases].
Objective: To investigate the clinical characteristics of ankylosing spondylitis (AS) combined Andersson lesion (AL). Methods: The clinical data of patients who were diagnosed as AS combined AL at Sun Yat-sen Memorial Hospital between January 2012 and December 2015 were reviewed retrospectively.SPSS 20.0 software was used for statistical analysis.Data of normal distribution was expressed by x±s (standard deviation) and that of abnormal distribution by median and range. Results: Fourteen patients were enrolled. Ten were male, median age (IQR, similarly hereinafter) was 46 (29-53) years, disease duration was 120 (54-150) months, 7 has symptom increased in the beginning, 6 has nerve compression symptom, 7 has kyphosis, and 4 has spinous tenderness or percussion pain in physical examination.Eleven of AL occurred in the thoracolumbar junction.Erythrocyte sedimentation rate was 24 (15-44) mm/1 h, C-reactive protein was 10 (5-18) mg/L, and Serum amyloid A was 19 (5-31) mg/L.All the 14 patients were divided into 2 groups, aggravated group (n=7) and none aggravated group (n=7) according to the symptom.It was no statistic difference between them about all the above indicators. Conclusion: Imageological diagnosis should be performed to identify Andersson lesion, while ankylosing spondylitis patients combined mechanical pain based on inflammatory back pain, or mainly with nerve compression symptom, tenderness or percussion pain, or spinous, even when inflammatory markers were normal.


[Dehumanizacja współczesnej medycyny: przyczyny i przeciwdziałanie].
A discussion of causes of dehumanisation in contemporary medicine and possible methods of preventing this situation. The causes can be divided into external, associated with the influence of the environment of civilisation, and internal, which constitute a form of aunwanted side effects" of the rapid progress of civilisation. The latter include reductionist thinking and axiological neutrality typical of natural sciences, increased import_ance of technology, and excessive specialisation combined with poor coordination of diagnostic work-up and treatment or the lack of such coordination. Possible preventive measures include a change in the model of medical education, consisting for instance in the inclusion of humanistic elements and a more holistic view of the patient, as well as a change in the health care model so that the diagnostic work-up and treatment would be coordinated mainly by the primary health care doctor.


AN-9 (Titan).
Titan is developing AN-9 for the potential treatment of various cancers. AN-9 is a histone deacetylase inhibitor analog of butyric acid that causes apoptosis of cancer cells through signaling cellular differentiation. In March 2001, a phase I/II study involving patients with liver tumors was initiated. By November 2001, enrollment had been completed in a second phase II study of refractory non-small-cell lung cancer (NSCLC). In June 2003, Titan began enrollment for a phase IIb trial of AN-9 in combination with docetaxel in patients with NSCLC.


The Clinical Significance of Pollen and Fungi Concentrations for Allergic Rhinitis: A Three-Year Study.
The relationship between disease severity and exposure to allergens in allergic rhinitis (AR) patients is not fully clarified presently. We aimed to detect the correlation between airborne pollen and fungi concentrations in a Mediterranean region with symptom scores. A total of 98 patients suffering from AR rated their symptoms at the time of exacerbation using the Total 5 Symptoms Score (T5SS) and the Visual Analogue Scale (VAS). Patients' quality of life (QoL) was estimated by using either disease-specific (Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and mini-RQLQ) or generic (Short-Form 36 (SF-36) and Beck Depression Inventory (BDI)) questionnaires. All patients' responses were correlated with aerobiological data. Skin prick tests (SPTs) were used to detect sensitivities to the most common registered pollen and fungi species. A significant positive correlation between total pollen and fungi counts and disease-specific questionnaires was found only for the RQLQ. Accordingly, a significant positive correlation was found between total pollen and fungi counts and T5SS (r = 0.655, p = 0.021), with breathing (r = 0.620, p = 0.032) and sneezing (r = 0.660, p = 0.020) being strongly affected. Moreover, a tendency toward a higher VAS score was found as total pollen and fungi counts increased (r = 0.523, p = 0.081). We found a significant correlation between patients' symptoms and pollen and fungal air concentrations. Our results emphasize the clinical significance of pollen and fungi maps in everyday clinical practice.


[A cross-sectional study of impaired fasting glycaemia and diabetes mellitus in rural residents of Lanxi, Heilongjiang].
To investigate the current status of impaired fasting glycaemia (IFG), diabetes mellitus (DM) and correlated factors, as well as on the awareness, treatment and control rate of diabetes mellitus in rural residents of Lanxi, Heilongjiang. Cross-sectional and cluster sampling method was carried out on 3480 residents over 35 years of age, in rural residents of Lanxi Pingshan, Heilongjiang province. To male, female and all, the detecting rate of IFG were 5.06%, 4.38% and 4.68% respectively, and the standardization rate of IFG became 4.71%, 4.24% and 4.47% respectively. The prevalence rates of DM were 7.85%, 6.57% and 7.15% but after standardization, they became 7.22%, 6.62% and 6.80% respectively. Results did not show statistical difference between sex and the level of fasting glycaemia (chi2 = 2.725, P = 0.256). The prevalence rates of IFG and DM increased with age and difference was seen between age and fasting glycaemia level (chi2 = 58.115, P= 0.000). Data from multivariable stepwise analysis showed that age, smoking, BMI and high triglyceride were the significant factors in fasting glycaemia level, and the ORs (95% CI) were 1.518 (1.360-1.694), 1.277 (1.134-1.439), 1.187 (1.014-1.391) and 1.754 (1.385-2.220) respectively. The rates of awareness, treatment and control rate in DM were 12.74%, 9.43% and 4.72% respectively while the treatment rate among those who knew the disease was 74.07%. Our result showed that the isolating rate of IFG and the prevalence rate DM were high in this region, but the awareness, treatment and control rate in DM were low. It is essential to strengthen health promotion program on diabetic knowledge and to elevate the primary and secondary prevention in the rural of Heilongjiang, so as to raise the rate of control.


Self-esteem, social support, collectivism, and the thin-ideal in Latina undergraduates.
Thin-ideal internalization (TII) reflects agreement that thinness equates with beauty. TII is a risk factor for body dissatisfaction and eating pathology; this phenomenon and its correlates, however, are just beginning to be studied in Latina undergraduates. This study examined the ability of self-esteem, social support, and collectivism to predict TII in 279 Latina undergraduates. It was hypothesized that higher levels of self-esteem, social support, and collectivism would predict lower levels of TII. Cross-sectional data were analyzed using multiple regression; the model was significant, p<.01. Although both self-esteem and social support negatively correlated with thin-ideal internalization, only self-esteem accounted for a significant amount of variance. Results indicate that investigations of self-esteem as a protective factor against TII in Latina undergraduates would be fruitful, as would how self-esteem and social support affect the relationship between TII and other variables. Implications and limitations are discussed.


Past, present and future of therapies in pediatric sarcomas.
Limited progress has been made over the past 30 years in improving the outcome of patients with high-risk pediatric sarcomas. The 5-year overall survival rate remains at 20% or less with metastatic sarcomas. Therefore, current and future research is focused on the identification and development of molecular or biological agents targeting the pathogenic pathways in sarcomas, either alone or in combination with conventional chemotherapy. To this end, the most promising activity has been seen with IGF-1 receptor antibodies and mTOR inhibitors. Other agents of interest are oncolytic viruses, epigenetic modulators (e.g., histone deacetylase inhibitors), immune modulators (e.g., muramyl tripeptide phosphatidylethanolamine) and other biological agents (e.g., trabectedin). In addition to the development of novel drugs, the other major area of recent focus is developing immune therapies, such as dendritic cell vaccines and adoptive immunotherapy for treating pediatric sarcomas. This article discusses the successes, the failures and the future direction of these therapies.


Molecular cloning and characterization of a novel carotenoid cleavage dioxygenase 1 from Lycium chinense.
Carotenoids are key precursor for aroma compounds in plants. Although the fruit of Lycium chinense contains numerous carotenoids, the formation mechanism of aroma compounds in L. chinense is still poorly understood. In this study, a new carotenoid cleavage dioxygenase (termed LmCCD1) was identified from the leaves of L. chinense. Expression analysis by semiquantitative PCR reveals that LmCCD1 gene is expressed in different tissues of L. chinense, and dominant expression of LmCCD1 gene was found in leaves, flowers, and ripe fruits. In addition, the expression level of LmCCD1 in fruits is in accordance with the content of β-ionone. Finally, recombinantly expressed LmCCD1 can cleave β-carotene and lycopene to produce β-ionone and pseudoionone in in vitro assays. These results indicate that LmCCD1 a novel carotenoids cleavage dioxygenase gene that may regulate the metabolic pathways responsible for aroma metabolite production (such as β-ionone and pseudoionone) in L. chinense has been identified.


Pro-Inflammatory Cytokines in Nasopharyngeal Aspirate From Hospitalized Children With Respiratory Syncytial Virus Infection With or Without Rhinovirus Bronchiolitis, and Use of the Cytokines as Predictors of Illness Severity.
Respiratory syncytial virus (RSV) and human rhinovirus (HRV) respiratory infection in children induce production of inflammatory interleukins (ILs) in the respiratory epithelium. As IL(s) determine the severity of illness, the purpose of this study was to identify the pro-inflammatory IL(s) that could be predictor(s) of clinical severity. One hundred and fifteen patients <2 years old with bronchiolitis due to RSV and /or HRV and 38 controls were selected from a hospital and an outpatient clinic. Clinical data of all patients were recorded. Severity was defined by the number of days with oxygen need. Nasopharyngeal aspirates (NPA) were collected to perform viral diagnosis by quantitative reverse transcription and polymerase chain reaction (qRT-PCR) and to quantify ILs: TNF-α, IL-10, IL-6, IL-1β, and IL-8, by flow cytometry. Simple and multiple regression and receiver operating characteristic (ROC) curves were used for statistical analysis. Of the patients selected 60 were single RSV, 28 RSV associated to HRV, and 27 single HRV. All patients (115) showed significantly higher IL levels when compared with controls. Levels of IL-6, IL-1β, and IL-8 detected in NPA from RSV single and associated to HRV were significantly higher than HRV infected and positively associated with days requiring O2.Levels of IL-6, IL-1β, and IL-8 detected in NPA from patients infected with RSV only or with both RSV and HRV are increased, and any of those 3 cytokines may have a predictive value for the number of days with need of supplemental oxygen.


AIDS: Perceptions and Misperceptions among Students of a Nigerian University.
The AIDS pandemic has led to the global clamouring for its control. This work was aimed at assessing the level and factors that determine the awareness of undergraduate Students of Usmanu Dandfodiyo University, Sokoto. In a descriptive cross-sectional study, a total of 450 students were recruited by means of multistage and simple random sampling techniques. Overall, there is a knowledge gap on aetiology, mode of transmission and preventive measures with only 40.2% and 38.5% of the respondents having adequate knowledge and indicated their willingness to learn more about AIDs respectively. Age (P<0.05), Sex (P<0.005) and number of years spent in the University (P<0.025) are important determinants of level of AIDS knowledge. This finding could be as a result of strong interactions between the social environment and human sexuality. Hence, student bodies should be involved in reproductive health programmes. Key words: awareness, university students, AIDS.


Predictors of Severe Morbidity After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Patients With Colorectal Peritoneal Carcinomatosis.
Severe morbidity after cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is, besides the obvious short-term consequences, associated with impaired long-term outcomes. The risk factors for severe morbidity in patients with peritoneal carcinomatosis (PC) of colorectal origin are poorly defined. This study aimed to identify risk factors for severe morbidity after CRS + HIPEC in patients with colorectal PC. Patients with colorectal PC who underwent CRS + HIPEC between 2007 and 2015 were categorized and compared between those with and those without severe morbidity. Risk factors were identified using logistic regression analysis. Morbidity was graded according to the Clavien-Dindo classification, with grade 3 or higher indicating severe morbidity. This study included 211 patients, of whom 53 patients (25.1%) experienced morbidity of grade 3 or higher. The identified risk factors for severe morbidity were extensive prior surgery [odds ratio (OR) 4.3], a positive recent smoking history (OR 4.0), a poor physical performance status (OR 2.9), and extensive cytoreduction (OR 1.2 per additional resection). Patients with a greater number of risk factors more often had severe morbidity and higher reoperation, readmission, and mortality rates. Furthermore, an internally validated preoperative prediction model for severe morbidity with an area under the curve of 70% was constructed. The current study identified risk factors for severe morbidity after CRS + HIPEC in patients with colorectal PC. Patients with a combination of risk factors have a substantial risk of severe morbidity and therefore should be carefully selected for CRS + HIPEC. The preoperative decision model can be a valuable additional tool in this process of patient selection.


Recurrent vascular myelopathy. Report of a case with autopsy.
A case of ischemic myelopathy which was marked by two clinical episodes, separated by a 4-month interval and affecting the same level of the spinal cord, is reported. A wide-ranging search through the literature shows that the recurrent type of ischemic vascular myelopathy is very rare.


A typology of health marketing research methods--combining public relations methods with organizational concern.
Research plays a critical role throughout virtually every conduit of the health services industry. The key terms of research, public relations, and organizational interests are discussed. Combining public relations as a strategic methodology with the organizational concern as a factor, a typology of four different research methods emerges. These four health marketing research methods are: investigative, strategic, informative, and verification. The implications of these distinct and contrasting research methods are examined.


Effects of 3-hydroxybutyrate on the hypoxic and reoxygenated atria from fed and fasted rats.
When exposed to hypoxia, the isolated atria from fed rats released lactate into the medium and underwent a decline of the peak developed tension and pacemaker frequency. The atria from 24-h fasted rats showed a rise in the resting tension together with a greater decline of the pacemaker rate and a lower lactate output than those from fed rats. The exposure to 5 mM 3-hydroxybutyrate caused only a small and brief decline in the pacemaker rate in the fed rats atria indicating that ketone bodies are able to exert only a minor detrimental effect on the hypoxic atria. Since the lactate output remained unaffected, this effect cannot be ascribed to a lowering in the energy supply from anaerobic glycolysis. On the contrary, 3-hydroxybutyrate improved the post-hypoxic recovery of the peak tension in the atria from fasted rats. This finding may be reflecting an anaplerotic role of 3-hydroxybutyrate, thus suggesting that in addition to glucose a second substrate is needed to meet the energy demand in the reoxygenated atria from fasted rats.


Chronic Enzyme Replacement to the Brain of a Late Infantile Neuronal Ceroid Lipofuscinosis Mouse Has Differential Effects on Phenotypes of Disease.
Late infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal inherited neurodegenerative disease caused by loss of lysosomal protease tripeptidyl peptidase 1 (TPP1). We have investigated the effects of chronic intrathecal (IT) administration using enzyme replacement therapy (ERT) to the brain of an LINCL mouse model, in which locomotor function declines dramatically prior to early death. Median lifespan was significantly extended from 126 days to >259 days when chronic IT treatment was initiated before the onset of disease. While treated animals lived longer and showed little sign of locomotor dysfunction as measured by stride length, some or all (depending on regimen) still died prematurely. One explanation is that cerebrospinal fluid (CSF)-mediated delivery may not deliver TPP1 to all brain regions. Morphological studies support this, showing delivery of TPP1 to ventral, but not deeper and dorsal regions. When IT treatment is initiated in severely affected LINCL mice, lifespan was extended modestly in most but dramatically extended in approximately one-third of the cohort. Treatment improved locomotor function in these severely compromised animals after it had declined to the point at which animals normally die. This indicates that some pathology in LINCL is reversible and does not simply reflect neuronal death.


Factors associated with postpartum depressive symptoms among women who conceived with infertility treatment.
Infertility treatment experiences may accumulate and influence postpartum psychological well-being among women with infertility. However, the association between infertility treatment experiences and postpartum depressive symptoms remained unclear. This cross-sectional survey aimed to describe depressive symptom scores of 180 women, who conceived while undergoing infertility treatment, at 2-6 months after childbirth, and to explore factors, including infertility history and treatment experiences, associated with postpartum depressive symptoms. Data were collected via telephone interviews and patient record reviews. Postpartum depressive symptoms were measured using the Edinburgh Postnatal Depression Scale, with a cutoff score of 10. The prevalence of postpartum depressive symptoms was 34.4 %. Higher perceived stress levels after childbirth than before undergoing infertility treatment, a duration of infertility diagnosis longer than three years, maternal age >35 years, pregnancy conceived through in vitro fertilization (IVF), and experiencing all three lines of infertility treatment, namely ovarian stimulation, intrauterine insemination, and IVF, were associated with a higher risk of postpartum depressive symptoms. Breastfeeding, social support, and baby sex in line with stated preference were negatively associated with postpartum depressive symptoms. There were no significant interactions between the variables. The women's infertility history and treatment experiences were found to have influenced their postpartum depressive symptoms, especially among women who had a long duration of infertility, conceived through IVF, and had received all lines of infertility treatment.


Validity and internal consistency of EQ-5D-3L quality of life tool among pre-dialysis patients with chronic kidney disease in Sri Lanka, a lower middle-income country.
EQ-5D-3L is a generic QOL tool used mainly in economic evaluations. Burden of Chronic Kidney Disease (CKD) is rising in Sri Lanka. Assessing the validity of generic QOL tools creates new opportunities of their utilization among patients with CKD. A cross-sectional study was conducted among 1036 CKD patients, selected using the simple random sampling technique. The validity was tested with six a-priori hypotheses. These included construct validity assessments, evaluating convergent validity and performing known group comparisons. EQ-5D-3L, Short Form-36 (SF-36) were used to assess QOL. Center for Epidemiological Studies Depression Scale (CES-D-20) and General Health Questionnaire-12 (GHQ-12) were used to assess the presence of depression and psychological distress respectively. Internal consistency of the whole tool and when each item is removed was assessed by Cronbach alpha. The response rate was 99.2%. Majority of participants were males (n = 646,62.4%) in the age category of 41-60 (n = 530; 51.2%). Most were in either stage 4 or 5 of CKD (n = 646,75.1%). The summary measures of SF-36, positively and significantly correlated with the EQ-5D-3L index and VAS scores (p<0.001). EQ-5D-3L QOL scores were significantly different between the group with depression and without as measured by CES-D-20 (p<0.001). Assessed using GHQ-12, similar significance was detected between the group with psychological distress and without (p<0.001). The Cronbach alpha was 0.834 and when each item was removed, ranged from 0.782 to 0.832. EQ-5D-3L is a valid generic QOL tool with satisfactory internal consistency to be used among CKD patients in the pre-dialysis stage.


2,5-cis-2,3,5-Trisubstituted tetrahydrofurans from the diastereomixture of 2,4-disubstituted 1,3-dioxepins via stereomutation.
A diastereoselective ring contraction of the diastereomixture of 2,4-disubstituted 1,3-dioxepins to 2,5-cis-2,3,5-trisubstituted tetrahydrofurans was achieved using TfOH in DMF. The reaction appears to proceed via a chair-like transition state, in which stereomutation of the oxocarbenium occurred, followed by an aldol-type cyclization.


A case of erythrophagocytic T4 lymphoma. Immunological and morphological peculiarities.
One case of T-cell lymphoma with atypical malignant cells is reported. Some of the clinical features, morphological characteristics and functional activity (erythrophagocytosis) of malignant cells suggested malignant histiocytosis. The malignant disease started with splenomegaly and developed with hepatomegaly, bone marrow infiltration, discrete lymphadenopathy and leukaemic picture. Proliferated cells were characterized by ambiguity. In addition to phagocytic capability, presence of complement receptors and ultrastructural features proper to the macrophagic lineage, the cells expressed T-cell determinants (E receptors, T3, T4 and T11 antigens) and were peroxidase and esterase-negative. Erythrocytes were partially or completely dehaemoglobinized and presented the phenomenon of autolysis in different stages of development. Because this lymphoma is difficult to diagnose and apparently resistant to therapy, its recognition and further study are warranted.


Case Report: Management of Recurrent Ovarian Squamous Cell Carcinoma With PD-1 Inhibitor.
Malignant transformations, such as ovarian squamous cell carcinoma (SCC) in ovarian mature cystic teratoma (OMCT), are rare tumors. The management of recurrent disease is still a challenge, and the gene mutations involved remain unclear. We herein report a recurrent case of ovarian SCC with a PIK3CA gene variation and immunohistochemical staining of programmed death-ligand 1 (PD-L1) >10%. This patient achieved clinical remission after platinum-based effective chemotherapy and programmed death 1 (PD-1) immunotherapy.


Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease.
IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance. In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined. Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals. A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD. Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.


Injectable bioactive calcium-magnesium phosphate cement for bone regeneration.
Novel injectable and degradable calcium-magnesium phosphate cement (CMPC) with rapid-setting characteristic was developed by the introduction of magnesium phosphate cement (MPC) into calcium phosphate cement (CPC). The calcium-magnesium phosphate cement prepared under the optimum P/L ratio exhibited good injectability and desired workability. It could set within 10 min at 37 degrees C in 100% relative humidity and the compressive strength could reach 47 MPa after setting for 48 h, indicating that the prepared cement has relatively high initial mechanical strength. The results of in vitro degradation experiments demonstrated the good degradability of the injectable CMPC, and its degradation rate occurred significantly faster than that of pure CPC in simulated body fluid (SBF) solution. It can be concluded that the novel injectable calcium-magnesium phosphate cement is highly promising for a wide variety of clinical applications, especially for the development of minimally invasive techniques.


NMR probes for measuring magnetic fields and field dynamics in MR systems.
High-resolution magnetic field probes based on pulsed liquid-state NMR are presented. Static field measurements with an error of 10 nanotesla or less at 3 tesla are readily obtained in 100 ms. The further ability to measure dynamic magnetic fields results from using small ( approximately 1 microL) droplets of MR-active liquid surrounded by susceptibility-matched materials. The consequent high field homogeneity allows free induction decay signals lasting 100 ms or more to be readily achieved. The small droplet dimensions allow the magnetic field to be measured even in the presence of large gradients. Highly sensitive detection yields sufficient SNR to follow the relevant field evolution without signal averaging and at bandwidths up to hundreds of kHz. Transient, nonreproducible effects and drifts are thus readily monitored. The typical application of k-space trajectory mapping has been demonstrated. Potential further applications include characterization, tuning, and maintenance of gradient systems as well as the mapping of the static field distribution of MRI magnets. Connection of the probes to a standard MR spectrometer is similar to that used for imaging coils.


Association between a novel mutation in SLC20A2 and familial idiopathic basal ganglia calcification.
Familial idiopathic basal ganglia calcification (FIBGC) is a rare, autosomal dominant disorder involving bilateral calcification of the basal ganglia. To identify gene mutations related to a Chinese FIBGC lineage, we evaluated available individuals in the family using CT scans. DNA was extracted from the peripheral blood of available family members, and both exonic and flanking intronic sequences of the SLC20A2 gene were amplified by PCR and then sequenced. Non-denaturing polyacrylamide gel electrophoresis (PAGE) was used to confirm the presence of mutations. Allele imbalances of the SLC20A2 gene or relative quantity of SLC20A2 transcripts were evaluated using qRT-PCR. A novel heterozygous single base-pair deletion (c.510delA) within the SLC20A2 gene was identified. This deletion mutation was found to co-segregate with basal ganglia calcification in all of the affected family members but was not detected in unaffected individuals or in 167 unrelated Han Chinese controls. The mutation will cause a frameshift, producing a truncated SLC20A2 protein with a premature termination codon, most likely leading to the complete loss of function of the SLC20A2 protein. This mutation may also lead to a reduction in SLC20A2 mRNA expression by approximately 30% in cells from affected individuals. In conclusion, we identified a novel mutation in SLC20A2 that is linked to FIBGC. In addition to the loss of function at the protein level, decreasing the expression of SLC20A2 mRNA may be another mechanism that can regulate SLC20A2 function in IBGC individuals. We propose that the regional expression pattern of SLC20A1 and SLC20A2 might explain the unique calcification pattern observed in FIBGC patients.


Oral health assessment of older adults living in long-term care facilities by non-dental professionals: a systematic review protocol of instruments.
Regular oral health assessment among older adults living in long-term care facilities (LTCF) can improve their oral health. Different instruments have been developed and used to evaluate the oral health of institutionalised older people by non-dental professionals. These instruments must demonstrate adequate measurement properties. This systematic review aims to examine the studies describing the instruments employed to assess the oral health of older adults living in LTCF by non-dental professionals. The study will also evaluate the measurement properties of such instruments using the checklist proposed by the Consensus-based Standards to select health Measurement Instruments (COSMIN). Studies describing the development of instruments for assessing oral health of institutionalised older adults by non-dental professionals will be included. Studies assessing at least one measurement property (validity, reliability or responsiveness) will be also considered. Electronic searches will be conducted on MEDLINE (PubMed, Ovid), Embase, Web of Science, Scopus and LILACS databases. Two independent reviewers will select the studies and will extract data concerning the characteristics of the research and the instrument. The measurement properties will be evaluated using the COSMIN checklist. The Grading of Recommendations, Assessment, Development and Evaluation approach will be used to grade the quality (or certainty) of evidence and strength of recommendations. No ethical approval is required. The results will be submitted for publication to a peer-review journal and presented at relevant conferences. CRD42020191479.


Phenotypic characterization of lymphocytes infiltrating synovial tissue from patients with rheumatoid arthritis: analysis of lymphocytes isolated from minced synovial tissue by dual immunofluorescent staining.
The phenotypic markers of mononuclear cells in synovial tissue from 19 patients with active rheumatoid arthritis (RA) were identified by a dual immunofluorescent method. The mononuclear cells were isolated from synovial tissue by mechanical disaggregation and an enzymatic digestion technique. The results revealed a marked reduction in CD4+2H4+ cells (suppressor inducer T cells) and an increment in CD4+4B4+ cells (helper T cells) among CD4+ cells in synovial tissue. The percentage of CD8+CD11b+ cells (suppressor effector T cells) was significantly lower in synovial tissue than in peripheral blood from patients with RA, resulting in an increased percentage of CD8+CD11b-- cells (cytotoxic T cells). The synovial tissue had higher percentages of pan B cells (B1+ cells), differentiated B cells (B1+B2-- cells) and plasma cells (PCA-1+ cells). These findings suggest that a combination of the increment in helper T cells, the reduction in suppressor T cells, and the increment in differentiated B cells may lead to excessive production of autoantibodies.


[The biochemical profile of calves' liver in the course of diarrhea during the first 10 days of life].
The total protein and total bilirubin levels as well as the GOT, GPT, alkaline phosphatase, GGTP and beta-glucuronidase activity in the blood serum and faeces from 121 diarrhoeic, Friesian-Holstein calves, aged from 1 to 10 days were investigated. As a control the results obtained in the previous investigations were used. Simultaneously the microbiological and histopathological examinations were performed. The changes of certain parameters in the blood serum, in the first 10 days of life, were parallel in both healthy and sick animals. The increase in alkaline phosphatase, GOT and GPT activity in calves with diarrhoea was observed. These changes may suggest the liver function damage during the neonatal calf diarrhoea. The decrease in GGTP activity, in the light of relationship between this enzyme and alkaline phosphatase activity, indicate the disturbances in intestinal absorption of colostral fraction of GGTP. The activity of beta-glucuronidase may be the sensitive index of liver function and indicate the range and the intensity of necrotic and/or dystrophic lesions. The activity of GOT and GPT in the faeces may be used as an indicator of liver function in the calves with diarrhoea while the additional investigations to explain the relationship between alkaline phosphatase, GGTP and beta-glucuronidase activity in faeces and intestinal lesions are needed.


Perioperative considerations of pyruvate dehydrogenase complex deficiency: a case report of two consecutive anesthesia.
Pyruvate dehydrogenase complex (PDHC) deficiency is a rare mitochondrial disorder caused by a genetic mutation affecting the activity of the PDHC enzyme, which plays a major role in the tricarboxylic cycle. Few cases of surgery or anesthesia have been reported. Moreover, there is no recommended anesthetic method. A 24-month-old child with a PDHC deficiency presented to the emergency room with respiratory failure, mental decline, systemic cyanosis, and lactic acidosis. During hospitalization period, the patient presented with pneumothorax, pneumoperitoneum, and multiple air pockets in the heart. Two surgeries were performed under general anesthesia using an inhalational anesthetic agent. The patient was discharged with home ventilation. Anesthesiologists should be wary of multiple factors when administering anesthesia to patients with PDHC deficiency, including airway abnormalities, acid-base imbalance, intraoperative fluid management, selection of appropriate anesthetics, and monitoring of lactic acid levels.


Brugia malayi and Acanthocheilonema viteae: antifilarial activity of transglutaminase inhibitors in vitro.
The possible involvement of transglutaminase-catalyzed reactions in survival of adult worms, microfilariae (mf), and infective larvae of the filarial parasite Brugia malayi was studied in vitro by using the specific pseudosubstrate monodansylcadaverine (MDC) and the active-site inhibitors cystamine or iodoacetamide. These inhibitors significantly inhibited parasite mobility in a dose-dependent manner. This inhibition was associated with irreversible biochemical lesions followed by filarial death. A structurally related, inactive analog of MDC, dimethyldansylcadaverine, did not affect the mobility or survival of the parasites. Adult worms failed to release mf when they were incubated in the presence of MDC or cystamine, and this inhibitory effect on mf release was concentration dependent. Similar embryostatic and macrofilaricidal effects of MDC were observed in Acanthocheilonema viteae adult worms. These studies suggest that transglutaminase-catalyzed reactions may play an important role in the growth, development, and survival of filarial parasites.


The Diagnosis and Treatment of Behavioral Disorders in Dementia.
Behavioral disorders such as aggressiveness, agitation, delusions, disinhibition, affect lability, and apathy arise in more than 90% of patients with dementia. Behavioral disorders are a major challenge and the greatest stress factor in everyday life for nursing personnel and for family members caring for the patient. This review is based on relevant publications retrieved by a selective literature search in the PubMed, Cochrane Library, and German S3 guideline databases with the search terms "behavioral disorders," "non-cognitive disorders," and "challenging behavior," in conjunction with "dementia" and "behavioral and psychological symptoms of dementia." Behavioral disorders regularly accompany dementing illness and have identifiable and treatable somatic and environment-related causes. They should be treated symptomatically, both with non-pharmacological measures and with drugs. Memory therapy (d = 0.47), ergotherapy (d = 0.72), music therapy (d = 0.62), and physical exercise (d = 0.68) are effective, as are antidementia drugs (galantamine: p = 0.04, donepezil: p = 0.01, rivastigmine: p = 0.02, memantine: p = 0.004). Risperidone is the drug of choice to combat agitation and aggressiveness (d = 0.33) as well as dementia and hallucinations (d = 0.5). Citalopram can be recommended for the treatment of depression in patients with dementia (p = 0.05). Because of an improved evidence base, the latest version of the German S3 guideline on the diagnosis and treatment of dementia places greater emphasis on non-pharmacological treatments for behavioral disorders in dementia than it did in the past. The global efficacy of such treatments against behavioral disorders is well documented. Nonetheless, because of the heterogeneity of interventions and varying standards of assessment, the evidence for the utility of certain specific methods in the treatment of specific behavioral disorders is still limited. More research is needed in this area.


The Prostate Cancer Cells Resistant to Docetaxel as in vitro Model for Discovering MicroRNAs Predictive of the Onset of Docetaxel Resistance.
On the grounds that miRNAs present in the blood of prostate cancer (PCa) patients are released in the growth medium by PCa cells, it is conceivable that PCa cells resistant to docetaxel (DCT) (DCTR) will release miRNAs that may be found in PCa patients under DCT therapy if resistant PCa cells appear. We isolated DCTR clones respectively from 22Rv1 and DU-145 PCa cell lines and performed through next-generation sequencing (NGS) the miRNAs profiles of the released miRNAs. The analysis of the NGS data identified 105 and 1 miRNAs which were differentially released in the growth medium of the 22Rv1/DCTR and DU-145/DCTR clones, respectively. Using additional filters, we selected 12 and 1 miRNA more released by all 22Rv1/DCTR and DU-145/DCTR clones, respectively. Moreover, we showed that 6 of them were more represented in the growth medium of the DCTR cells than the ones of DCT-treated cells. We speculated that they have the pre-requisite to be tested as predictive biomarkers of the DCT resistance in PCa patients under DCT therapy. We propose the utilization of clones resistant to a given drug as in vitro model to identify the differentially released miRNAs, which in perspective could be tested as predictive biomarkers of drug resistance in tumor patients under therapy.


Late presentation of infection as a complication of Dwyer anterior spinal instrumentation.
Delayed presentation of infection is a rare complication of anterior instrumentation and fusion for scoliosis. Three cases that followed the Dwyer procedure are reported. Pain was absent in these patients, but mild constitutional symptoms were present. An elevated erythrocyte sedimentation rate (ESR) is an important indicator of this complication. Two patients developed groin abscesses and sinuses as the hallmark of deep infection. Infection resolved after removal of instrumentation and local debridement.


Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder.
This study examines cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with attention-deficit/hyperactivity disorder. Two hundred seven participants aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1-3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing and titrated to optimal behavioral response. Heart rate, systolic blood pressure (BP), diastolic BP, and electrocardiograms were assessed at baseline, end of blinded optimization, and over a 1-year open-label maintenance phase. During acute titration, GUAN-IR decreased heart rate, systolic BP, and diastolic BP; DMPH increased heart rate, systolic BP, diastolic BP, and corrected QT (QTc) interval; COMB increased diastolic BP, but had no effects on heart rate, systolic BP, or QTc. During maintenance, GUAN-IR-associated decreases in heart rate and DMPH-associated increases in systolic BP returned to baseline values. Other variables across the three groups remained unchanged from the end of blinded titration. There were no discontinuations due to CV adverse events. GUAN-IR, DMPH, and COMB were well tolerated and safe. Expected changes in CV parameters during acute titration were seen in GUAN-IR and DMPH groups, with COMB values falling intermediately between the two other treatment groups. No serious CV events occurred in any participant. GUAN-IR- and DMPH-associated CV changes generally returned to baseline with sustained therapy. These data suggest that COMB treatment might attenuate long-term CV effects of GUAN-IR and stimulant monotherapy, possibly reducing risk of the small but statistically significant changes associated with either single treatment. Clinicaltrials.gov Identifier: NCT00429273.


The limits of intensive feeding: maternal foodwork at the intersections of race, class, and gender.
Despite experiencing numerous barriers, mothers today confront increasing social pressure to embody perfection through their foodwork. A growing body of social science research identifies how gender and class inequality shape women's perceptions of food and their feeding strategies, but this research is thus far limited in its understanding of the roles that race and ethnic identity play in a mother's food landscape. Drawing on 60 in-depth interviews with a racially and economically diverse group of mothers, this paper examines how feeding young children is intertwined with contemporary ideas about child health as well as women's efforts to negotiate race, class, and gender hierarchies. Extending Hays' concept of intensive mothering, rich descriptions of feeding children reveal how mothers in this study are discursively engaged with what I call an 'intensive feeding ideology' - the widespread belief that good mothering is synonymous with intensive food labour. Drawing on intersectional theory, this article discusses the limits of an intensive feeding ideology, particularly for poor and middle-class mothers of colour. The findings contribute to an understanding of how power relations are embedded within food ideologies and how mothers of young children attempt to negotiate them.


Layer-stacked tin disulfide nanorods in silica nanoreactors with improved lithium storage capabilities.
A new structure of layered materials, layer-stacked nanorod, has been fabricated through an entirely new template-engaged structural transformation methodology. The formation of layer-stacked hexagonal tin disulfide (SnS(2)) nanorods has been demonstrated as an example by using tetragonal tin (Sn) nanorods as sacrificing templates and silica (SiO(2)) as nanoreactors. In addition, the structural transformation process probably involves the formation of orthorhombic tin sulfide (SnS) nanorods as an intermediate product. The rod-like morphology and single-crystal feature of the Sn templates are well preserved in both SnS(2) and SnS products due to the nanoscale confinement in silica. Owing to its unique structural characteristics, the SnS(2)-SiO(2) nanorod anode exhibits excellent capacity retention and improved rate capability, facilitating its application in lithium ion batteries with long cycle life and high power density.


Human cerebral activity evoked by motion reversal and motion onset. A PET study.
In this PET study, we have investigated the human brain activity evoked by a visual motion paradigm commonly used to measure motion-related visual evoked potentials (VEPs). Because standard PET activation studies have been performed with motion along four axes, we first determined the pattern of brain activation when motion was restricted to a single axis. Motion back and forward along a single horizontal axis compared with a static condition revealed weak differential activations in the cuneus and the parietal cortex. Human area MT/V5 (middle temporal area) was hardly activated at all in this subtraction. Additional functional MRI experiments proved that MT/V5 activity is significantly higher for motion along four axes than for motion along a single axis. Secondly, we attempted to isolate the pattern of brain activity related to the reversal of motion direction and to the onset of motion, i.e. two transient motion components commonly used in measuring motion-related VEPs. To that end, we added a continuous linear contrast modulation, that reached maximum contrast at reversal or onset of motion, and compared both conditions with a contrast-modulated static or continuous motion condition. Subtraction of the static random dot pattern condition from the single-axis motion reversal condition, both contrast-modulated, revealed three significant activations: the anterior parieto-occipital sulcus, the lateral sulcus and the anterior claustrum. Additional analysis showed that these activations were not due to motion appearance or disappearance, but were due to the combination of motion reversal and contrast modulation. Hence, these activations do not reflect the motion reversal transient per se. In order to isolate a metabolic response to the reversal transient per se, we used a conjunction analysis, which suggests that activity in human MT/V5, the cuneus and a parietal insular region could underlie the motion reversal VEP in our experiments. Subtraction of the static random dot pattern condition from the single-axis motion onset condition, both contrast-modulated, revealed a single significant activation in the posterior cingulate cortex. Although the significance of this activation is unclear, it adds further evidence for the visual function of this region.


Who Wrote This Clinical Practice Guideline?
The American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guidelines address a variety of otolaryngologic diseases and/or procedures. It may seem reasonable to create these guidelines by assembling a team of expert clinicians familiar with the pertinent clinical issues and the available evidence, with debate and eventual agreement leading to recommendations. However, trustworthy clinical practice guidelines are in fact created via a defined process to assemble a guideline development group composed of diverse stakeholders: clinician generalists and specialists, content experts, methodologists, physicians and nonphysicians, patients, and advocates. Such a guideline development group can create a valuable and trusted guideline for clinicians and affected patients.


Winter-annual pasture as a supplement for beef cows.
In each of two experiments, 120 pregnant beef cows were stratified by body condition score, BW, breed, and age, randomly divided into six groups of 20, and assigned to one of six 5.1-ha bermudagrass (Cynodon dactylon [L.] Pers.) pastures (two replicates/ treatment) in early January to evaluate the use of winter-annual pasture as a supplement. All cows in Exp. 1 and 2 had ad libitum access to bermudagrass/dallisgrass (Paspalum dilatatum Poir.) hay plus three treatments: 1) a concentrate-based supplement fed 3 d/wk, 2) limit grazing on winter-annual pasture 2 d/wk (7 hr/ d; 0.04 ha x cow(-1) x grazing d(-1)), or 3) limit grazing on winter-annual pasture 3 d/wk (7 hr/d; 0.04 ha x cow(-1) x grazing d(-1)) sod-seeded into a portion of the pasture until mid-May. The seeded portion of pastures in Exp. 1 was planted with a mixture of wheat (Triticum aestivum L.) and rye (Secale cereale L.), but annual ryegrass (Lolium multiflorum Lam.) was added to the seed mixture in Exp. 2. In mid-May, cows were blocked by treatment and the previous sorting factors, randomly assigned to six new groups of 20, and placed on the six perennial pastures until calves were weaned. Groups of cows were exposed to a bull for 60 d beginning in mid-May. In Exp. 1 and 2, limit-grazing winter-annual pasture compared to the concentrate-based supplement or limit grazing 2 vs 3 d/wk did not affect (P > 0.15) cow BW. In Exp. 1, cows limit grazed on winter-annual pasture had a lower (P = 0.05) body condition score than cows fed the concentrate-based supplement in the early spring. However, in Exp. 2, cows limit grazed on winter-annual pasture had higher (P < or = 0.07) body condition score than cows fed the concentrate-based supplement. The conception rate of cows in Exp. 1 and 2 did not differ (P > 0.22) between cows fed concentrate-based supplements and cows limit grazed on winter-annual pasture. In Exp. 2, cows limit grazed 2 d/wk tended to have a greater (P = 0.10) conception rate than cows limit grazed 3 d/wk. In Exp. 1 and 2, birth weight, total gain, BW, and ADG of calves were not affected (P > 0.15) by treatment. We conclude that wheat and rye pasture is a marginal supplement for lactating beef cows. However, cows limit grazed 2 d/wk on winter-annual pasture of wheat, rye, and annual ryegrass as a supplement maintained BW and body condition score as well as cows fed the concentrate-based supplement. But, grazing pasture 3 vs 2 d/wk did not seem to affect performance of cows.


How to help the oral pathologist in making an accurate diagnosis.
A biopsy is a valuable diagnostic tool in clinics. In this procedure, the sample tissue is obtained in order to study its structure both macro and microscopically, thus making it possible to establish a final diagnosis. Some clinicians are surprised and disappointed when the report from the oral pathologist comes as "not from the representative area and "inadequate specimen size", instead of a final diagnosis. To avoid such disappointments and to make the best utilization of the skills of the oral pathologist, certain ideas have been suggested. Right from the history taking to the clinical examination to the operative findings, the clinician can pave the way to a conclusive histopathological diagnosis.


Controlled syngas production by electrocatalytic CO2 reduction on formulated Au25(SR)18 and PtAu24(SR)18 nanoclusters.
Syngas, a gaseous mixture of CO and H2, is a critical industrial feedstock for producing bulk chemicals and synthetic fuels, and its production via direct CO2 electroreduction in aqueous media constitutes an important step toward carbon-negative technologies. Herein, we report controlled syngas production with various H2/CO ratios via the electrochemical CO2 reduction reaction (CO2RR) on specifically formulated Au25 and PtAu24 nanoclusters (NCs) with core-atom-controlled selectivities. While CO was predominantly produced from the CO2RR on the Au NCs, H2 production was favored on the PtAu24 NCs. Density functional theory calculations of the free energy profiles for the CO2RR and hydrogen evolution reaction (HER) indicated that the reaction energy for the conversion of CO2 to CO was much lower than that for the HER on the Au25 NC. In contrast, the energy profiles calculated for the HER indicated that the PtAu24 NCs have nearly thermoneutral binding properties; thus, H2 production is favored over CO formation. Based on the distinctly different catalytic selectivities of Au25 and PtAu24 NCs, controlled syngas production with H2/CO ratios of 1 to 4 was demonstrated at a constant applied potential by simply mixing the Au25 and PtAu24 NCs based on their intrinsic catalytic activities for the production of CO and H2.


Antibody effector mechanisms in myasthenia gravis-pathogenesis at the neuromuscular junction.
Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies that are either directed to the muscle nicotinic acetylcholine receptor (AChR) or to the muscle-specific tyrosine kinase (MuSK). These autoantibodies define two distinct subforms of the disease-AChR-MG and MuSK-MG. Both AChR and MuSK are expressed on the postsynaptic membrane of the neuromuscular junction (NMJ), which is a highly specialized region of the muscle dedicated to receive and process signals from the motor nerve. Autoantibody binding to proteins of the postsynaptic membrane leads to impaired neuromuscular transmission and muscle weakness. Pro-inflammatory antibodies of the human IgG1 and IgG3 subclass modulate the AChR, cause complement activation, and attract lymphocytes; together acting to decrease levels of the AChR and AChR-associated proteins and to reduce postsynaptic folding. In patients with anti-MuSK antibodies, there is no evidence of loss of junctional folds and no apparent loss of AChR density. Anti-MuSK antibodies are predominantly of the IgG4 isotype, which functionally differs from other IgG subclasses in its anti-inflammatory activity. Moreover, IgG4 undergoes a posttranslational modification termed Fab arm exchange that prevents cross-linking of antigens. These findings suggest that MuSK-MG may be different in etiological and pathological mechanisms from AChR-MG. The effector functions of IgG subclasses on synapse structure and function are discussed in this review.


SPECT perfusion imaging with 123I-HIPDM in a patient with pulmonary embolism.
The use of 123I-N,N,N'trimethyl-N'-2-hydroxy-3-methyl-5-iodobenzyl-1,3-propanediami ne (123I-HIPDM) as a lung perfusion tracer in a patient with pulmonary embolism is shown. 123I-HIPDM is compared with 99mTc-labeled human albumin microspheres (HAM) using both planar and tomographic (SPECT) imaging. Pulmonary segmental defects are shown by 123I-HIPDM as well as by HAM, with a slightly better definition of perfused areas. Tomograms better show segmental shape of perfusion defects. 123I-HIPDM may be proposed as lung perfusion tracer for both clinical and experimental purposes.


Abnormal reward circuitry in anorexia nervosa: A longitudinal, multimodal MRI study.
Anorexia nervosa (AN) is a debilitating illness and existing interventions are only modestly effective. This study aimed to determine whether AN pathophysiology is associated with altered connections within fronto-accumbal circuitry subserving reward processing. Diffusion and resting-state functional MRI scans were collected in female inpatients with AN (n = 22) and healthy controls (HC; n = 18) between the ages of 16 and 25 years. Individuals with AN were scanned during the acute, underweight phase of the illness and again following inpatient weight restoration. HC were scanned twice over the same timeframe. Based on univariate and multivariate analyses of fronto-accumbal circuitry, underweight individuals with AN were found to have increased structural connectivity (diffusion probabilistic tractography), increased white matter anisotropy (tract-based spatial statistics), increased functional connectivity (seed-based correlation in resting-state fMRI), and altered effective connectivity (spectral dynamic causal modeling). Following weight restoration, fronto-accumbal structural connectivity continued to be abnormally increased bilaterally with large (partial η2 = 0.387; right NAcc-OFC) and moderate (partial η2 = 0.197; left NAcc-OFC) effect sizes. Increased structural connectivity within fronto-accumbal circuitry in the underweight state correlated with severity of eating disorder symptoms. Taken together, the findings from this longitudinal, multimodal neuroimaging study offer converging evidence of atypical fronto-accumbal circuitry in AN. Hum Brain Mapp 37:3835-3846, 2016. © 2016 Wiley Periodicals, Inc.


Early myocardial surgical revascularization after ST-segment elevation myocardial infarction in multivessel coronary disease: bridge therapy is the solution?
Many ST-segment elevation myocardial infarction (STEMI) patients have a multivessel disease that initially require percutaneous coronary intervention (PCI) of the culprit vessel but subsequently may require coronary artery bypass graft (CABG) of nonculprit vessels. Evidence supports staged revascularization, but the identification of optimal strategies (percutaneous or surgical), the timing and the management of antiplatelet therapy after recent PCI with stenting are matters of great controversies. In our retrospective registry, we have enrolled 21 patients presenting with STEMI and multivessel disease, who underwent PCI of the culprit vessel only and then CABG of nonculprit vessels. Demographic, clinical, echocardiographic, angiographic findings, preoperative score, surgical data and postoperative complications were collected. At 21.6 ± 15.6 months follow-up death, reinfarction and/or cardiovascular and noncardiovascular events were recorded. Patients were 62 ± 9 years old and had in the most cases a good ejection fraction. At angiography, the culprit lesion was right coronary artery in 16 patients (76%). Angiographic characteristics excluded a staged PCI (SYNTAX score = 31.6 ± 7.4) and European System for Cardiac Operative Risk Evaluation II resulted low (1.46 ± 1.01). Following the indication to cardiac surgery after Heart Team discussion, the withdrawal of oral P2Y12 inhibitor was planned and tirofiban intravenous was started. Off-pump CABG was performed after 7.2 ± 3.2 days. No death, reinfarction and/or cardiovascular and noncardiovascular events occurred at follow-up. We can conclude that a careful preoperative selection is mandatory for a good postoperative course and long-term survival and that early-staged CABG can, however, be performed using bridge therapy, also after STEMI.


A model structure of the muscle protein complex 4Ca2+.troponin C.troponin I derived from small-angle scattering data: implications for regulation.
We report here a model structure for 4Ca2+.troponin C.troponin I derived from small-angle X-ray and neutron scattering data using a Monte Carlo modeling method. In this model, troponin I appears as a spiral structure that wraps around 4Ca2+.troponin C which adopts an extended dumbbell conformation similar to that observed in the crystal structures of troponin C. The troponin I spiral has the approximate dimensions of an alpha-helix and winds through the hydrophobic "cups" in each globular domain of troponin C. The model is consistent with a body of previously published biochemical data on the interactions between troponin C and troponin I, and suggests the molecular mechanism for the Ca(2+)-sensitive switch that regulates the muscle contraction/relaxation cycle involves a signal transmitted via the central spiral region of troponin I.


Monoclonal immunoglobulin deposition disease associated with membranous features.
Very few cases of non-organized and non-Randall-type monoclonal immunoglobulin deposition disease (MIDD) associated with membranous features have been reported. Information on clinicopathological features and prognosis in this entity is limited. We reviewed 5443 renal biopsies processed at our department, and identified three patients with MIDD associated with membranous features. We evaluated clinicopathological features and outcomes in these patients. All patients had proteinuria, and one patient developed nephrotic syndrome. Renal insufficiency was not observed. Cryoglobulin or monoclonal protein in serum and urine was not detected. A renal biopsy showed thickening of the glomerular capillary walls and spike formation. Tubulointerstitial and vascular alterations were mild or absent. Immunofluorescence studies revealed granular IgG3-kappa deposits in two patients and IgG1-kappa deposits in one patient, along the glomerular capillary walls. Immunofluorescence studies using antibodies specific for gamma-heavy chain Fab containing C(H)1 domain, C(H)2 domain and C(H)3 domain did not show any apparent deletion. On confocal microscopy, glomerular colocalization of light and heavy chains was observed. Electron microscopy showed predominant subepithelial granular deposits without distinct ultrastructural organization. All patients were treated with steroids, and good effects were observed. A follow-up renal biopsy performed in one patient showed histological improvements. No patient developed myeloma or other haematological malignancy during the course of follow-up (mean 44 months). MIDD associated with membranous features is an extremely rare but distinctive entity. Our study suggests glomerular deposition of a nondeleted whole immunoglobulin molecule. Patients with this entity appear to respond well to steroid therapy.


Efficacy of the Cervical Vertebral Maturation Method: A Systematic Review.
The present systematic review was carried out to evaluate both qualitatively and quantitatively the effectiveness of the cervical vertebral maturation (CVM) method in predicting the pubertal growth spurt. PubMed, PMC, Scopus, SciELO, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched. The research included every article published from 1970 to June 2019, featuring the keywords: ("cervical vertebrae" OR ("cervical" AND "vertebrae") AND ("orthodontics" OR "growth and development" OR ("growth" AND "development") OR ("growth"). The Preferred Reporting Items for Reporting Systematic Reviews and Meta Analyses (PRISMA) protocol was adopted, and quality assessments modified from the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) and the "Standards for the Reporting of Diagnostic Accuracy Studies" (STARD) were performed to conduct this systematic review. Initially, 1284 articles were found. All the articles were then examined, and 43 studies met the inclusion criteria. Sixteen articles had low-quality scores, 25 had moderate scores, and 2 had high scores. The results showed a moderate to high statistically significant correlation between the CVM and other maturation methods. Overall, the CVM method can be considered an effective method and may be used with other skeletal indices for the radiographic assessment of skeletal maturity, and also to identify the growth peak in growing patients.


Dynamic Treatment Regimes.
A dynamic treatment regime consists of a sequence of decision rules, one per stage of intervention, that dictate how to individualize treatments to patients based on evolving treatment and covariate history. These regimes are particularly useful for managing chronic disorders, and fit well into the larger paradigm of personalized medicine. They provide one way to operationalize a clinical decision support system. Statistics plays a key role in the construction of evidence-based dynamic treatment regimes - informing best study design as well as efficient estimation and valid inference. Due to the many novel methodological challenges it offers, this area has been growing in popularity among statisticians in recent years. In this article, we review the key developments in this exciting field of research. In particular, we discuss the sequential multiple assignment randomized trial designs, estimation techniques like Q-learning and marginal structural models, and several inference techniques designed to address the associated non-standard asymptotics. We reference software, whenever available. We also outline some important future directions.


[Overlapping, interdependence or complementarity, interprofessional collaboration between nurse practitioners and other health professionals in Ontario].
The Naylor Report (2015) states that nurse practitioners (NP) are still underutilized in Canada despite positive evidence of their work and the benefits they provide to health systems and, more generally, the health of the population. Why are nurse practitioners not more actively involved in the Canadian health care system? A socio-historical literature review showed that there is overlap, interdependence or complementarity between the role of NPs and that of other health professionals and that this concerns their status, training as well as the scope of their practice. The development of an interprofessional collaborative approach, although supported by most professional nursing associations in Canada, is difficult to establish in NP practice and training. This article describes the emergence of the role of NPs in Canada and provides an update on the current status of their integration in the health system with reference to the Ontario example. It provides insight into the overlap and zones of complementarity or interdependence between NPs and other health professionals. In conclusion, the authors call for improved governance by the contribution of a new collaborative contract with other health professionals. This contract should be based on the interdependence of practices and the complementarity of roles between all health professionals including NPs.


Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification.
A key regulatory point in the control of fatty acid (FA) oxidation is thought to be transport of FAs across the mitochondrial membrane by carnitine palmitoyltransferase I (CPT I). To investigate the role of CPT I in FA metabolism, we used in vivo electrotransfer (IVE) to locally overexpress CPT I in muscle of rodents. A vector expressing the human muscle isoform of CPT I was electrotransferred into the right lateral muscles of the distal hindlimb [tibialis cranialis (TC) and extensor digitorum longus (EDL)] of rats, and a control vector expressing GFP was electrotransferred into the left muscles. Initial studies showed that CPT I protein expression peaked 7 days after IVE (+104%, P<0.01). This was associated with an increase in maximal CPT I activity (+30%, P < 0.001) and a similar increase in palmitoyl-CoA oxidation (+24%; P<0.001) in isolated mitochondria from the TC. Importantly, oxidation of the medium-chain FA octanoyl-CoA and CPT I sensitivity to inhibition by malonyl-CoA were not altered by CPT I overexpression. FA oxidation in isolated EDL muscle strips was increased with CPT I overexpression (+28%, P<0.01), whereas FA incorporation into the muscle triacylglycerol (TAG) pool was reduced (-17%, P<0.01). As a result, intramyocellular TAG content was decreased with CPT I overexpression in both the TC (-25%, P<0.05) and the EDL (-45%, P<0.05). These studies demonstrate that acute overexpression of CPT I in muscle leads to a repartitioning of FAs away from esterification and toward oxidation and highlight the importance of CPT I in regulating muscle FA metabolism.


The immune response in a dog to Encephalitozoon cuniculi infection.
The immune response to Encephalitozoon cuniculi infection in a dog was investigated by means of the indirect fluorescent antibody test, the leucocyte migration inhibition test and the radial immunodiffusion test for serum IgG and IgM levels. Specific antibodies were detected within 7 days of infection and they persisted for 370 days. A cell-mediated immune response was detected from Day 13 following infection until Day 97. Histopathological examination showed plasma cell infiltration of the kidneys, meninges, lung, bladder, smooth muscle and spleen.


Immune System Involvement in Specific Pain Conditions.
Chronic pain is a significant problem worldwide and is the most common disability in the United States. It is well known that the immune system plays a critical role in the development and maintenance of many chronic pain conditions. The involvement of the immune system can be through the release of autoantibodies, in the case of rheumatoid arthritis, or via cytokines, chemokines, and other inflammatory mediators (i.e. substance P, histamine, bradykinin, tumor necrosis factor, interleukins, and prostaglandins). Immune cells, such as T cells, B cells and their antibodies, and microglia are clearly key players in immune-related pain. The purpose of this review is to briefly discuss the immune system involvement in pain and to outline how it relates to rheumatoid arthritis, osteoarthritis, fibromyalgia, complex regional pain syndrome, multiple sclerosis, and diabetic neuropathy. The immune system plays a major role in many debilitating chronic pain conditions and we believe that animal models of disease and their treatments should be more directly focused on these interactions.


Noninvasive Imaging of Epicardial and Endocardial Potentials With Low Rank and Sparsity Constraints.
In this study, we explore the use of low rank and sparse constraints for the noninvasive estimation of epicardial and endocardial extracellular potentials from body-surface electrocardiographic data to locate the focus of premature ventricular contractions (PVCs). The proposed strategy formulates the dynamic spatiotemporal distribution of cardiac potentials by means of low rank and sparse decomposition, where the low rank term represents the smooth background and the anomalous potentials are extracted in the sparse matrix. Compared to the most previous potential-based approaches, the proposed low rank and sparse constraints are batch spatiotemporal constraints that capture the underlying relationship of dynamic potentials. The resulting optimization problem is solved using alternating direction method of multipliers. Three sets of simulation experiments with eight different ventricular pacing sites demonstrate that the proposed model outperforms the existing Tikhonov regularization (zero-order, second-order) and L1-norm based method at accurately reconstructing the potentials and locating the ventricular pacing sites. Experiments on a total of 39 cases of real PVC data also validate the ability of the proposed method to correctly locate ectopic pacing sites.


The role of external actors in shaping migrant health insurance in Thailand.
The role of external actors in national health policy in aid-independent countries has received relatively little attention in the literature, despite the fact that influence continues to be exerted once financial support is curtailed as countries graduate from lower income status. Focusing on a specific health policy in an aid-independent country, this qualitative study explores the role of external actors in shaping Thailand's migrant health insurance. Primary data were collected through in-depth interviews with eighteen key informants from September 2018 to January 2019. The data were analysed using thematic analysis, focusing on three channels of influence, financial resources, technical expertise and inter-sectoral leverage, and their effect on the different stages of the policy process. Given Thailand's export orientation and the importance of reputational effects, inter-sectoral leverage, mainly through the US TIP Reports and the EU carding decision, emerged as a very powerful channel of influence on priority setting, as it indirectly affected the migrant health insurance through efforts aimed at dealing with problems of human trafficking in the context of labour migration, especially after the 2014 coup d'état. This study helps understand the changed role external actors can play in filling health system gaps in aid-independent countries.


Association of AKT1 with verbal learning, verbal memory, and regional cortical gray matter density in twins.
AKT1, encoding the protein kinase B, has been associated with the genetic etiology of schizophrenia and bipolar disorder. However, minuscule data exist on the role of different alleles of AKT1 in measurable quantitative endophenotypes, such as cognitive abilities and neuroanatomical features, showing deviations in schizophrenia and bipolar disorder. We evaluated the contribution of AKT1 to quantitative cognitive traits and 3D high-resolution neuroanatomical images in a Finnish twin sample consisting of 298 twins: 61 pairs with schizophrenia (8 concordant), 31 pairs with bipolar disorder (5 concordant) and 65 control pairs matched for age, sex and demographics. An AKT1 allele defined by the SNP rs1130214 located in the UTR of the gene revealed association with cognitive traits related to verbal learning and memory (P = 0.0005 for a composite index). This association was further fortified by a higher degree of resemblance of verbal memory capacity in pairs sharing the rs1130214 genotype compared to pairs not sharing the genotype. Furthermore, the same allele was also associated with decreased gray matter density in medial and dorsolateral prefrontal cortex (P < 0.05). Our findings support the role of AKT1 in the genetic background of cognitive and anatomical features, known to be affected by psychotic disorders. The established association of the same allelic variant of AKT1 with both cognitive and neuroanatomical aberrations could suggest that AKT1 exerts its effect on verbal learning and memory via neural networks involving prefrontal cortex.