The clinical importance of the thyroid nodules during anti-tumor necrosis factor therapy in patients with axial spondyloarthritis.
The clinical importance of the thyroid nodules in patients with axial spondyloarthritis (ax-SpA) rests with the need to exclude thyroid malignancy. The aim of this study is to assess the risk of thyroid malignancy in ax-SpA patients receiving anti-TNF therapy. From September 2015 until December 2015, 70 patients diagnosed with ax-SpA were included in the research. Forty of the patients had received anti-TNF therapy, and 30 of the patients were anti-TNF naive. All cases were screened for the presence of nodules in the thyroid gland with ultrasound. Of the patients that received anti-TNF therapy, 15 (37.5%); and of the anti-TNF naive patients, 11 (36.7%) had thyroid nodule(s). Four patients from the anti-TNF group underwent fine needle aspiration biopsy of the nodules, and two of them were diagnosed with papillary thyroid carcinoma. None of the nodules in anti-TNF naive patients required biopsy. When compared to the normal population, the standardized incidence ratio (SIR) was found to be increased in both male (SIR 2.03, 95% CI 1.9 to 18) and female (SIR 2.7, 95% CI 2.6 to 24) cases. It is not yet established whether the development of cancer during the treatment process is the effect of the treatment or if it is a part of the natural course of the disease or if it is coincidental. We saw a mild increase in thyroid malignancies in ax-SpA patients who received anti-TNF therapy. Therefore, we believe that the thyroid gland should also be taken into consideration while screening for malignancy before anti-TNF therapy.


A possible role for catabolin in tissue remodelling and repair.
Catabolin is a recently discovered polypeptide of 17 000 molecular weight which stimulates connective and skeletal tissue cells to degrade their extracellular matrix. It is produced by a variety of cell types and is believed to be part of a family of cellular messengers which interact to control tissue remodelling and repair in both physiological and pathological situations.


Photochromic Radical Complexes That Show Heterolytic Bond Dissociation.
Photochromic materials have been widely used in various research fields because of their variety of photoswitching properties based on various molecular frameworks and bond breaking processes, such as homolysis and heterolysis. However, while a number of photochromic molecular frameworks have been reported so far, there are few reports on photochromic molecular frameworks that show both homolysis and heterolysis depending on the substituents with high durability. The biradicals and zwitterions generated by homolysis and heterolysis have different physical and chemical properties and different potential applications. Therefore, the rational photochromic molecular design to control the bond dissociation in the excited state on demand expands the versatility for photoswitch materials beyond the conventional photochromic molecular frameworks. In this study, we synthesized novel photochromic molecules based on the framework of a radical-dissociation-type photochromic molecule: phenoxyl-imidazolyl radical complex (PIC). While the conventional PIC shows the photoinduced homolysis, the substitution of a strong electron-donating moiety to the phenoxyl moiety enables the bond dissociation process to be switched from homolysis to heterolysis. This study gives a strategy for controlling the bond dissociation process of the excited state of photochromic systems, and the strategy enables us to develop further novel radical and zwitterionic photoswitches.


Truncated TDP-43 proteoforms diagnostic of frontotemporal dementia with TDP-43 pathology.
Biomarkers of TDP-43 pathology are needed to distinguish frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) from phenotypically related disorders. While normal physiological TDP-43 is not a promising biomarker, low-resolution techniques have suggested truncated forms of TDP-43 may be specific to TDP-43 pathology. To advance biomarker efforts for FTLD-TDP, we employed a high-resolution structural technique to characterize TDP-43 post-translational modifications in FTLD-TDP. High-resolution mass spectrometry was used to characterize TDP-43 proteoforms in brain tissue from FTLD-TDP, non-TDP-43 dementias and neuropathologically unaffected cases. Findings were then verified in a larger cohort of FTLD-TDP and non-TDP-43 dementias via targeted quantitative mass spectrometry. In the discovery phase, truncated TDP-43 identified FTLD-TDP with 85% sensitivity and 100% specificity. The verification phase revealed similar findings, with 83% sensitivity and 89% specificity. The concentration of truncated TDP-43 proteoforms-in particular, in vivo generated C-terminal fragments-have high diagnostic accuracy for FTLD-TDP. Discovery: Truncated TDP-43 differentiates FTLD-TDP from related dementias. Verification: Truncated TDP-43 concentration has high accuracy for FTLD-TDP. TDP-43 proteoforms <28 kDa have highest discriminatory power for TDP-43 pathology.


Role of Prealbumin in Predicting the Prognosis of Severely and Critically Ill COVID-19 Patients.
Most critically ill patients experience malnutrition, resulting in a poor prognosis. This study aimed to evaluate the association of prealbumin (PAB) with the prognosis for severely and critically ill coronavirus disease 2019 (COVID-19) patients and explore factors related to this association. Patients with laboratory-confirmed COVID-19 from West Campus of Union Hospital in Wuhan from January 29, 2020 to March 31, 2020 were enrolled in this study. Patients were classified into the PAB1 (150-400 mg/L; N = 183) and PAB2 (< 150 mg/L; N = 225) groups. Data collection was performed using the hospital's electronic medical records system. The predictive value of PAB was evaluated by measuring the area under the receiver-operating characteristic (AUROC) curve. Patients were defined as severely or critically ill based on the Guidance for COVID-19 (7th edition) by the National Health Commission of China. During this analysis, 316 patients had severe cases and 65 had critical cases. A reduced PAB level was associated with a higher risk of mortality and a longer hospital stay. The AUROC curve for the prognosis based on the PAB level was 0.93, with sensitivity of 97.2% and specificity of 77.6%. For severe cases, a lower level of PAB was associated with a higher risk of malnutrition, higher NK cell counts, and lower B lymphocyte counts; these factors were not significant in critical cases. C-reactive protein and nutritional status mediated the association between PAB and prognosis. This retrospective analysis suggests that the PAB level on admission is an indicator of the prognosis for COVID-19.


Expression of TGF-alpha, EGF, and EGF receptor in fetal rat lung.
To define the distribution of transforming growth factor-alpha (TGF-alpha) and its relationship to epidermal growth factor (EGF) and EGF receptor in lung development and to determine whether epithelial cells produce TGF-alpha, we studied the expression of TGF-alpha, EGF, and their receptor in late-gestation fetal rat lung and in cultured fetal rat lung cells. TGF-alpha, EGF, and EGF receptor were colocalized in epithelial and smooth muscle cells of bronchioles and bronchi and in epithelial cells of saccules. Epithelial cells cultured from late-gestation fetal rat lung transcribe TGF-alpha and EGF receptor mRNA and produce TGF-alpha and EGF receptor proteins. Cultured fibroblasts contained EGF receptor mRNA, but no detectable TGF-alpha mRNA. These results demonstrate fetal lung epithelial cells are a source for TGF-alpha and suggest that TGF-alpha might act through an autocrine or paracrine mechanism with epithelial and mesenchymal cells. The colocalization of TGF-alpha and EGF suggests that these growth factors might act in parallel in lung development.


The impact of demographic trends on hospital surgical care.
The projected increase in numbers and percentages of elderly people has great potential impact on health services generally. Only rarely, however, has the impact of age of patients on a surgical service been quantitated. Two hundred fifty-five consecutive laparotomies performed in men older than 65 years of age were compared with 174 consecutive laparotomies in men younger than 65 years of age, all from a Veterans Administration Medical Center experience. Morbid factors, including mortality, increased with age with the greatest increments over the age of 75 years and especially over the age of 85 years. An intensity-of-care index was devised; the intensity-of-care ratios progressively increased with age. Unless there are significant technical advances, future surgical results will not be as good as they are at present, since the patient composition will be less favorable. Any estimates of the costs of surgical care in the future must include the projected age of patients as a major factor.


Semiautomated matching and seed position location for implanted ribbons.
A difficult, error-prone, and time consuming problem in brachytherapy is the determination of the three-dimensional (3-D) positions of implanted seeds. To triangulate 3-D seed positions, the corresponding seed images in radiographs taken at different parallax (gantry) angles must be identified (matched). With only two radiographs, there is an inherent problem of ambiguity in matching individual seed images. The use of the assignment algorithm cannot bypass this ambiguity. However, when seeds are implanted within ribbons, their positions in 3-D space can be determined accurately and (almost always) without ambiguity. This follows because the matching of ribbon images is much less ambiguous than the matching of individual seed images. We describe a semi-automated procedure to match the ribbon images on two radiographs, determine the 3-D loci of the ribbons, and locate the 3-D position of each seed on each ribbon. The ribbon matching problem involves a double application of the assignment algorithm. After image matching, the 3-D locus of each ribbon is found from the intersection of the ray sets from its radiographic images and the analysis of a 3-D spanning tree through the derived ray set intersection points. The seed positions on a ribbon locus are determined by interpolation of equally spaced seed intervals along the 3-D ribbon locus. Experiments with a phantom show that for two radiographs separated by any parallax between 20 degrees and 90 degrees, our technique provides a systematic error in 3-D seed location of 3.0 mm, and a random error of less than 2 mm.


Increased temperature, not cardiac load, activates heat shock transcription factor 1 and heat shock protein 72 expression in the heart.
The expression of myocardial heat shock protein 72 (HSP72) postexercise is initiated by the activation of heat shock transcription factor 1 (HSF1). However, it remains unknown which physiological stimuli govern myocardial HSF1 activation during exercise. These experiments tested the hypothesis that thermal stress and mechanical load, concomitant with simulated exercise, provide independent stimuli for HSF1 activation and ensuing cardiac HSP72 gene expression. To elucidate the independent roles of increased temperature and cardiac workload in the exercise-mediated upregulation of left-ventricular HSP72, hearts from adult male Sprague-Dawley rats were randomly assigned to one of five simulated exercise conditions. Upon reaching a surgical plane of anesthesia, each experimental heart was isolated and perfused using an in vitro working heart model, while independently varying temperatures (i.e., 37 degrees C vs. 40 degrees C) and cardiac workloads (i.e., low preload and afterload vs. high preload and afterload) to mimic exercise responses. Results indicate that hyperthermia, independent of cardiac workload, promoted an increase in nuclear translocation and phosphorylation of HSF1 compared with normothermic left ventricles. Similarly, hyperthermia, independent of workload, resulted in significant increases in cardiac levels of HSP72 mRNA. Collectively, these data suggest that HSF1 activation and HSP72 gene transcriptional competence during simulated exercise are linked to elevated heart temperature and are not a direct function of increased cardiac workload.


Multilocus sequence typing and clonal population genetic structure of Cyclospora cayetanensis in humans.
To investigate the prevalence of Cyclospora cayetanensis in a longitudinal study and to conduct a population genetic analysis, fecal specimens from 6579 patients were collected during the cyclosporiasis - prevalent seasons in two urban areas of central China in 2011-2015. The overall incidence of C. cayetanensis infection was 1·2% (76/6579): 1·6% (50/3173) in Zhengzhou and 0·8% (26/3406) in Kaifeng (P 0·05). All the isolates clustered in the C. cayetanensis clade based on the small subunit ribosomal RNA gene sequence phylogenetic analysis. There were 45 specimens positive for all the five C. cayetanensis microsatellite loci, and formed 29 multilocus genotypes (MLGs). The phylogenetic relationships of 54 distinct MLGs (including 25 known reference MLGs), based on the concatenated multilocus sequences, formed three main clusters. A population structure analysis showed that the 79 isolates (including 34 known reference isolates) of C. cayetanensis produced three distinct subpopulations based on allelic profile data. In conclusion, we determined the frequency of C. cayetanensis infection in humans in Henan Province. The clonal population structure of the human C. cayetanensis isolates showed linkage disequilibrium and three distinct subpopulations.


Management of acute maxillary sinusitis in Finnish primary care. Results from the nationwide MIKSTRA study.
To study the management of acute maxillary sinusitis (AMS) in Finnish primary care and to compare it both to recommendations in national guidelines and to the management of other upper respiratory tract infections (URTI). A cross-sectional multi-centre epidemiological survey. Thirty primary care health centres in Finland. 7284 patients with symptoms of possible acute rhinosinusitis during one week in both November 1998 and November 1999. Symptoms and their duration, use of diagnostic tools, choice of antibiotics, patient outcomes. A total of 1601 patients were diagnosed as having AMS (12% of all patients with infectious disease). In 45% of cases the differentiation between AMS and URTI was based on clinical examination alone. Sinus ultrasound was the most common diagnostic tool used (38%). Sinus radiography or blood tests (CRP or leukocytes) were both studied in 8% of cases. AMS was diagnosed and treated with antibiotics also in the early stages of URTI when viruses are the most likely explanation. In total, 83% of patients with AMS received a prescription for antibiotics; the most common choice was amoxycillin (37%), doxycycline was used in 29% of cases, and macrolides in 15%. Antibiotics are prescribed for AMS 2 to 5 times more often than true disease incidence would suggest in Finland. The choice of antibiotics follows the guideline recommendations; however, use of macrolides is higher than recommended. Physicians feel strong pressure from patients to prescribe antibiotics for AMS. Primary care physicians need better support in the accurate diagnosis of AMS.


Immunohistological demonstration of calcitonin in endometrial carcinomas with and without argyrophil cells.
Sixteen endometrial carcinomas were studied by an immunoperoxidase method with anti-human calcitonin, 8 with and 8 without argyrophil cells. Calcitonin was demonstrated in 7 with and 2 without argyrophil cells. Calcitonin production was not associated with any specific histology of the endometrial carcinomas. Regardless of the existence of argyrophil cells, calcitonin was located in the apical portion or in the entire cytoplasm of the glandular tumor cells in the well differentiated adenocarcinomas. In a poorly differentiated adenocarcinoma and the adenosquamous carcinomas, it was found in many immature and squamous tumor cells as well as in some glandular tumor cells. The comparative studies between calcitonin and argyrophil granules in the endometrial carcinomas with argyrophil cells revealed that calcitonin was located in many tumor cells other than argyrophil cells. The extreme examples were 2 calcitonin-producing tumors without argyrophil cells. Calcitonin production of the endometrial carcinomas is a novel finding, but the biological significance of argyrophil cells remains to be further investigated.


Coronary artery aneurysms occurrence risk analysis between Kawasaki disease and LRP1B gene in Taiwanese children.
Background: Kawasaki disease (KD) is an acute and systemic vasculitis. Its complications in coronary artery aneurysms (CAA) make KD one of the leading causes of acquired cardiovascular diseases in childhood. Low density lipoprotein receptor-related protein 1B (LRP1B) is abundantly expressed in the medial layer of coronary arteries and involved in endothelium inflammations. Purpose: We aimed to identify the role of LRP1B in CAA formation during KD progression. Methods: we investigated genetic variations in LRP1B in a Taiwanese cohort of 258 KD patients (83 with CAA and 175 without CAA complications). We used univariate and multivariate regression analyses to identify the associations between LRP1B genetic variations and KD patients. Results: CAA formation in KD was significantly associated with the LRP1B (rs6707826) genetic variant (p = 0.007). By using multivariate regression analysis, significant correlations were observed between KD with CAA complications and the presence of the TT+TG genotypes for the LRP1B rs6707826 single-nucleotide polymorphism (full model: odds ratio = 2.82; 95% CI = 1.33-5.78). Conclusion: Our results suggest that genetic polymorphism of LRP1B gene may be used as a genetic marker for the diagnosis and prognosis of the CAA formation in KD and contribute to genetic profiling studies for personalized medicine.


Tiny telomere DNA.
We describe the design, synthesis and biophysical characterization of a novel DNA construct in which a folded quadruplex structure is joined to a standard double helix. Circular dichroism, gel electrophoresis, three-dimensional UV melting and differential scanning calorimetry were all used to characterize the structure. Rigorous molecular dynamics simulations were used to build a plausible atomic-level structural model of the DNA construct. This novel DNA construct provides a model for the duplex-quadruplex junction region at the end of chromosomal DNA and offers a system for the study of structure-selective ligand binding.


Advances in the pathogenesis and personalised treatment of paediatric asthma.
The diversity of pathology of severe paediatric asthma demonstrates that the one-size-fits-all approach characterising many guidelines is inappropriate. The term "asthma" is best used to describe a clinical syndrome of wheeze, chest tightness, breathlessness, and sometimes cough, making no assumptions about underlying pathology. Before personalising treatment, it is essential to make the diagnosis correctly and optimise basic management. Clinicians must determine exactly what type of asthma each child has. We are moving from describing symptom patterns in preschool wheeze to describing multiple underlying phenotypes with implications for targeting treatment. Many new treatment options are available for school age asthma, including biological medicines targeting type 2 inflammation, but a paucity of options are available for non-type 2 disease. The traditional reliever treatment, shortacting β2 agonists, is being replaced by combination inhalers containing inhaled corticosteroids and fast, longacting β2 agonists to treat the underlying inflammation in even mild asthma and reduce the risk of asthma attacks. However, much decision making is still based on adult data extrapolated to children. Better inclusion of children in future research studies is essential, if children are to benefit from these new advances in asthma treatment.


Effect of high blood flow on pulmonary vascular permeability to protein.
The elevated cardiac output associated with exercise increases lung lymph flow and may increase extravascular lung water. However, it is not known if extremely elevated cardiac output alters pulmonary vascular permeability. The hematocrit-protein method was used to determine the solvent drag reflection coefficient, an index of vascular permeability to proteins, in the isolated blood-perfused canine lung lobe. Microvascular pressure was obtained by double vascular occlusion. Lobes filtered fluid during perfusion at normal flow, 0.451 +/- 0.005 l/min (LF; n = 8), or high flow, 2.319 +/- 0.080 l/min (HF; n = 7). In the LF, venous pressure was elevated to 19.0 +/- 0.5 Torr to induce filtration, whereas Pv was 3.3 +/- 0.1 Torr in the HF. In HF vs. LF, respectively, arterial pressure was 61.4 +/- 7.1 vs. 28.0 +/- 1.0 Torr (P < 0.05), microvascular pressure was 31.9 +/- 3.0 vs. 22.2 +/- 0.9 Torr (P < 0.05), and sigma was 0.52 +/- 0.07 vs. 0.51 +/- 0.02 (P > 0.05). The fivefold increase in blood flow did not alter pulmonary vascular permeability to proteins; however, the capillary filtration coefficient was fivefold greater in the HF vs. LF group (0.328 +/- 0.059 vs. 0.067 +/- 0.007; P < 0.002). These data are compatible with enzyme activity measures indicating a direct linear relationship between blood flow rate and perfused pulmonary microvascular surface area. Although the data do not rule out the possibility of increased pulmonary vascular permeability to water during very elevated blood flow rates, the greater filtration rate during elevated flow is more likely related to increases in both microvascular pressure and surface area.


Autologous Transplantation of a Free Tenon's Graft for Repairing Excessive Bleb Leakage after Trabeculectomy: A Case Report.
To report a case of autologous transplantation of a free Tenon's graft to repair excessive bleb leakage after trabeculectomy. A 39-year-old Japanese woman presented with severe hypotony in her left eye. She had undergone trabeculectomy with mitomycin C 14 years ago. Slit-lamp examination showed an ischemic and ruptured bleb, excessive bleb leakage, and an extremely shallow anterior chamber. A large scleral defect was vaguely observed through the bleb conjunctiva. The hypotony was attributed to excessive bleb leakage. A surgical revision was required. First, the avascular bleb conjunctiva and the melted scleral flap were excised. A scleral defect was observed. Thick fibrotic tissue, i.e., the autologous Tenon's graft, was separated from the underlying sclera, cut to the desired size to cover the defect, and sutured to the sclera with 10-0 nylon sutures. Irrigation with balanced salt solution through the paracentesis confirmed deepening of the anterior chamber with no bleb leakage. In the current case, a layer of amniotic membrane was applied to cover the largely exposed sclera. Two weeks postoperatively, the surgical site was totally re-epi-thelialized with no aqueous leakage. Three months postoperatively, vascularization into the surgical site was observed. The intraocular pressure remained within normal levels without recurrent bleb leakage. Autologous transplantation of a free Tenon's graft successfully repaired excessive bleb leakage through a scleral defect after trabeculectomy. This technique is easier, safer, and may be more cost effective for repairing excessive bleb leakage after trabeculectomy than conventional management techniques.


Suppression of alcohol delirium tremens by baclofen administration: a case report.
Delirium tremens (DT) is a clinical condition that appears in some patients affected by severe alcohol withdrawal syndrome (AWS). DT represents a serious complication, being characterized by elevated morbidity and mortality. Benzodiazepines are presently the drug of choice; however their use is related to several side effects. Baclofen is a stereoselective gamma-aminobutyric acid (GABAB) receptor agonist. Recent studies show that baclofen is able to suppress alcohol withdrawal symptoms. At present there are no data on the effects of baclofen administration in AWS complicated by DT. Here, we report a case of DT successfully treated with baclofen. This result indicates that the efficacy of baclofen in the treatment of DT should be examined in future clinical trials.


Effect of rice bran oil spread on the physical, sensory and fatty acid profile of cake.
Studies were carried out to replace hydrogenated fat (HF) with rice bran oil (RBO) and two varieties of rice bran oil spread RBOS1 and RBOS2 in the preparation of cake. Physico-chemical properties, sensory properties, scanning electronic microscopic (SEM) study and fatty acid estimation with reference to trans fatty acids of cake made with control and experimental samples were studied. The best acceptable cake among the four i.e., RBOS2 cake was selected for consumer evaluation along with control (HF) cake. Results revealed that there was no significant difference in overall acceptability of cake made with HF and RBOS2. The internal structure and pore structure of RBOS2 cake was finer and smoother than the control cake as per SEM imaging. The pores within the core varied in diameter between 13.9 and 29.6 µm in control cake and between 16.9 and 58.6 µm in RBOS2 cake at 500 × magnification indicating good textural properties compared to HF cake. The fatty acids analysis results showed that the amount of total trans fatty acids (TFA) was 15.46% in HF cake, 3.56% in RBO cake, 4.54% in RBOS1 cake, and 3.78% in RBOS2 cake. The major trans fatty acids observed in all samples were elaidic acid (C18:1 trans-9) and Linolelidic acid (C18:2, trans-6). Elaidic acid was the highest in HF cake (6.64%) and the least in RBO cake (2.62%). Linolelidic acid was the highest in HF cake (8.48%) and the least in RBOS2 cake (0.91%). Trans Vaccenic acid was detected only in HF cake (0.34%). TFA content assumes significance in terms of its ill effects on the health of consumers, only if fat content is also high. Hence, consumption of the HF products might prove to be harmful, if consumed in large amounts and at higher frequencies. Therefore RBOS can be promoted as healthy fat for production of baked products.


The BMP4-Smad signaling pathway regulates hyperandrogenism development in a female mouse model.
Polycystic ovary syndrome is a common endocrine disorder and a major cause of anovulatory sterility in women at reproductive age. Most patients with polycystic ovary syndrome have hyperandrogenism, caused by excess androgen synthesis. Bone morphogenetic protein 4 (BMP4) is an essential regulator of embryonic development and organ formation, and recent studies have also shown that BMP4 may be involved in female steroidogenesis process. However, the effect of BMP4 on hyperandrogenism remains unknown. Here, using a female mouse model of hyperandrogenism, we found that ovarian BMP4 levels were significantly decreased in hyperandrogenism. Elevated androgens inhibited BMP4 expression via activation of androgen receptors. Moreover, BMP4 treatment suppressed androgen synthesis in theca cells and promoted estrogen production in granulosa cells by regulating the expression of steroidogenic enzymes, including CYP11A, HSD3B2, CYP17A1, and CYP19A1 Consistently, knockdown of BMP4 augmented androgen levels and inhibited estrogen levels. Mechanistically, Smad signaling rather than the p38 MAPK pathway regulated androgen and estrogen formation, thereby mediating the effect of BMP4. Of note, BMP4-transgenic mice were protected against hyperandrogenism. Our observations clarify a vital role of BMP4 in controlling sex hormone levels and offer new insights into intervention for managing hyperandrogenism by targeting the BMP4-Smad signaling pathway.


Workplace Heat Exposure Management in Indian Construction Workers Using Cooling Garment.
Construction workers are at high risk of heat-related illnesses during summer months in India. The personal cooling garment (PCG) is a microclimate assistive device that provides protection from heat stress. The applicability and efficacy of wearing PCG for the physiological and subjective responses were tested on 29 healthy construction workers at actual field worksites. During the test, the climatic conditions were 103.64 ± 38.3°F dry bulb temperature, 41.2 ± 13.4% relative humidity, and wet bulb globe temperature 91.43 ± 39.92°F. Mean weighted skin temperature was significantly lowered by 38.66 ± 33.98°F when wearing PCG as compared with wearing habitual clothing (HC), 32.36 ± 33.44°F ( p < .05). Mean sweat loss was also significantly lower when wearing PCG: 0.365 ± 0.257 kg as compared with wearing HC: 0.658 ± 0.342 kg ( p < .05). Heart rate, along with back and chest skin temperatures were significantly reduced with wearing PCG. The present study suggests that PCG provides an affordable way of alleviating the discomfort and physiological strain caused by environmental heat exposure.


Four-Lead Electrical Resistance Measurements in Bridgman Anvils.
A geometry is described which permits four-lead electrical determinations of the pressure coefficient of resistance of metals in Bridgman anvils. It is also possible in this geometry to mount more than one sample aild to make independent measurements on each sample simultaneously.


Lenticels are sites of initiation of microcracking and russeting in 'Apple' mango.
The mango cultivar 'Apple' is an important fruitcrop in Kenya, but it is highly susceptible to russeting. The objective was to establish whether lenticels predispose cv. 'Apple' mango to russeting. Fruit mass and surface area increased in a sigmoidal pattern with time. The frequency of lenticels per unit surface area decreased during development. The number of lenticels per fruit was constant. Lenticels were most frequent in the apex region and least common in the cheek and nak (ventral) regions. The cheek region also had lenticels with the largest core areas, whereas the lenticel core areas in the apex region were significantly smaller. Microscopy revealed stomata became covered over with wax deposits at 33 days after full bloom (DAFB). By 78 DAFB, periderm had formed beneath the pore. At 110 and 161 DAFB, cracks had developed and the periderm had extended tangentially and radially. The presence of lenticels increased the strain released upon excision of an epidermal segment, further strain releases occurred subsequently upon isolation of the cuticle and on extraction of the cuticular waxes. The number of lenticels per unit surface area was negatively correlated with the fruit surface area (r2 = 0.62 **), but not affected by fruit size. Mango cv. 'Apple' had fewer, larger lenticels and more russet, compared with 'Ngowe', 'Kitovu' or 'Tommy Atkins' mango. In cv. 'Apple', the lowest lenticel frequency, the largest lenticels and the most russeting occurred at a growing site at the highest altitude, with the highest rainfall and the lowest temperature. Moisture exposure of the fruit surface resulted in enlarged lenticels and more microcracking of the cuticle. Our results establish that russeting in 'Apple' mango is initiated at lenticels and is exacerbated if lenticels are exposed to moisture.


Harnessing low-density lipoprotein receptor protein 6 (LRP6) genetic variation and Wnt signaling for innovative diagnostics in complex diseases.
Wnt signaling regulates a broad variety of processes in both embryonic development and various diseases. Recent studies indicated that some genetic variants in Wnt signaling pathway may serve as predictors of diseases. Low-density lipoprotein receptor protein 6 (LRP6) is a Wnt co-receptor with essential functions in the Wnt/β-catenin pathway, and mutations in LRP6 gene are linked to many complex human diseases, including metabolic syndrome, cancer, Alzheimer's disease and osteoporosis. Therefore, we focus on the role of LRP6 genetic polymorphisms and Wnt signaling in complex diseases, and the mechanisms from mouse models and cell lines. It is also highly anticipated that LRP6 variants will be applied clinically in the future. The brief review provided here could be a useful resource for future research and may contribute to a more accurate diagnosis in complex diseases.


3-[(E)-(4-Chloro-benzyl-idene)amino]-1-phenyl-thio-urea.
In the title compound, C(14)H(12)ClN(3)S, the dihedral angle between the terminal benzene rings is 56.6 (2)°; the benzene rings lie to the same side of the mol-ecule. The major twist in the mol-ecule occurs around the C(ar)-N bond (ar is aromatic) [C-N-C-C = 49.9 (5)°]. The configuration about the N=C bond [1.271 (4) Å] is E. The amine H atoms lie on opposite sides of the mol-ecule with one forming an intra-molecular N-H⋯N(imine) hydrogen bond and an S(5) ring. In the crystal, centrosymmetric dimers are formed via {⋯HNC=S}(2) synthons.


Regional disparities in immunization services in Ghana through a bottleneck analysis approach: implications for sustaining national gains in immunization.
Immunization is considered one of the most cost effective public health interventions for reducing child morbidity, mortality and disability. The aim of this work is to describe the application of the Bottleneck analysis (BNA) process to assess gaps in immunization services in Ghana and implications for sustaining the gains in Immunization coverage. A national assessment was conducted in May 2015, through use of desk reviews, field visits and key informant interviews. Quantitative data were analysed with the BNA Tool (an excel-based tool) based directly on service coverage data and programme monitoring and review reports in Ghana. Outputs were generated based on service coverage indicators; supply side/health system factors (commodities, human resource and access), demand side (service utilisation) and quality/effective coverage. National targets were used as benchmarks to assess gaps in coverage indicators. In all, only 50% of regions and districts had health facilities with at least 80% of health care workers training provided in-service training on routine immunization; only 40% of district had communities with functional fixed or outreach EPI service delivery point and over 70% of regions and districts had challenges with effective coverage of infants aged 0-11 months fully immunized during the past year. Other key health system bottlenecks included, limited number of fixed and outreach sites, difficult to reach island communities along the Volta Basin, inadequate storage facilities for vaccines at lower levels, stock out of vaccines and auto destruct syringes and absence of updated policies/field guides at services delivery points/facilities. In addition, inadequate in-service training in routine Immunization and absence of good quality data were major challenges. Demand side bottlenecks included fear of mothers on the safety of multiple vaccines and limited active involvement of communities in Immunization service delivery. The BNA tool and approach provided data driven planning of health service in Ghana. This resulted in the development of regional and national operational plans for immunization and will be the baseline for evaluating the national programme in three years.


Endothelial to mesenchymal transition contributes to nicotine-induced atherosclerosis.
Rationale: Nicotine exposure via cigarette smoking is strongly associated with atherosclerosis. However, the underlying mechanisms remain poorly understood. The current study aimed to identify whether endothelial to mesenchymal transition (EndMT) contributes to nicotine-induced atherosclerosis. Methods: ApoE-/- mice were administered nicotine in their drinking water for 12 weeks. The effects of nicotine on EndMT were determined by immunostaining on aortic root and RNA analysis in aortic intima. In vitro nicotine-treated cell model was established on human aortic endothelial cells (HAECs). The effects of nicotine on the expression of EndMT-related markers, ERK1/2 and Snail were quantified by real-time PCR, western blot and immunofluorescent staining. Results: Nicotine treatment resulted in larger atherosclerotic plaques in ApoE-/- mice. The vascular endothelial cells from nicotine-treated mice showed mesenchymal phenotype, indicating EndMT. Moreover, nicotine-induced EndMT process was accompanied by cytoskeleton reorganization and impaired barrier function. The α7 nicotine acetylcholine receptor (α7nAChR) was highly expressed in HAECs and its antagonist could effectively relieve nicotine-induced EndMT and atherosclerotic lesions in mice. Further experiments revealed that ERK1/2 signaling was activated by nicotine, which led to the upregulation of Snail. Blocking ERK1/2 with inhibitor or silencing Snail by small interfering RNA efficiently preserved endothelial phenotype upon nicotine stimulation. Conclusion: Our study provides evidence that EndMT contributes to the pro-atherosclerotic property of nicotine. Nicotine induces EndMT through α7nAChR-ERK1/2-Snail signaling in endothelial cells. EndMT may be a therapeutic target for smoking-related endothelial dysfunction and cardiovascular disease.


Anticonvulsant and behavioural effects of the denatured venom of the social wasp Polybia occidentalis (Polistinae, Vespidae).
Several investigations demonstrate that neurotoxins isolated from venoms of spiders and wasps may exert specific and selective activity on structures of the mammalian CNS. In the present work we examine the neurological effects of the low molecular weight compounds of the denatured venom of the neotropical social wasp Polybia occidentalis in freely moving rats. Central administration of denatured venom decreased the duration of exploratory, elevation and grooming behaviours on the open field. Moreover, denatured venom inhibited convulsing action of bicuculline (ED50 57 microg/microl), picrotoxin (ED50 75 microg/microl) and kainic acid (ED50 44 microg/microl), although it was ineffective against pentylenetetrazole-induced seizures. Despite of its inhibitory activity, toxic effects on motor performance examined in the rotarod test were not found, not even in extremely high doses. Also, denatured venom moderately reduced the spontaneous locomotor activity at anticonvulsant doses. These findings may indicate that the denatured venom has anticonvulsant activity with scarce propensity to cause neurological side-effects. Further studies are necessary to isolate the active compound and establish its mechanism of action.


Population genomics of free-ranging Great Plains white-tailed and mule deer reflects a long history of interspecific hybridization.
Hybridization is a natural process at species-range boundaries that may variably promote the speciation process or break down species barriers but minimally will influence management outcomes of distinct populations. White-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus) have broad and overlapping distributions in North America and a recognized capacity for interspecific hybridization. In response to contemporary environmental change to any of one or multiple still-unknown factors, mule deer range is contracting westward accompanied by a westward expansion of white-tailed deer, leading to increasing interactions, opportunities for gene flow, and associated conservation implications. To quantify genetic diversity, phylogenomic structure, and dynamics of hybridization in sympatric populations of white-tailed and mule deer, we used mitochondrial cytochrome b data coupled with SNP loci discovered with double-digest restriction site-associated DNA sequencing. We recovered 25,018 SNPs across 92 deer samples from both species, collected from two regions of western Kansas. Eight individuals with unambiguous external morphology representing both species were of hybrid origin (8.7%), and represented the product of multi-generational backcrossing. Mitochondrial data showed both ancient and recent directional discordance with morphological species assignments, reflecting a legacy of mule deer males mating with white-tailed deer females. Mule deer had lower genetic diversity than white-tailed deer, and both mitochondrial and nuclear data suggest contemporary mule deer effective population decline. Landscape genetic analyses show relative isolation between the two study regions for white-tailed deer, but greater connectivity among mule deer, with predominant movement from north to south. Collectively, our results suggest a long history of gene flow between these species in the Great Plains and hint at evolutionary processes that purge incompatible functional genomic elements as a result of hybridization. Surviving hybrids evidently may be reproductive, but with unknown consequences for the future integrity of these species, population trajectories, or relative susceptibility to emerging pathogens.


[Prognostic value of the uterine doppler velocimetry at 20-24 gestation weeks for PIH and IUGR development in pregnancy].
Pathogenesis of pregnancy induced hypertension and intrauterine growth retardation is strictly connected with poor supply of the feto-maternal unit with well oxygenated blood rich in all nutritional substances. Monitoring of the pregnancy course and normal values estimation in the group of non-complicated pregnancies allows us to get PIH and IUGR prediction values of the uterine velocimetry. Main aims of the study were: estimation of the normal values for utcrine velocimetry in II and III trimester of pregnancy (S/D, RI, and PI); analysis of the prognostic usefulness of these parameters (between 20-24 gestation weeks) and importance of notch in FVW for development of PIH and IUGR later in pregnancy. We observed a decrease of uterine velocimetry parameters (mean values) in the course of normal pregnancy (19-40 gestation weeks). The sensitivity of the notch observation in 20-24 week in the uterine FVW for the prediction of PIH and/or IUGR (all study group) in the III trimester was 73,68% and the specificity 97,15%. The prognostic value of the examined pathology markers at 20-24 weeks was for notch or R >90% - 79,69% and notch or PI >90% - 70,31%. Normal pregnancy is characterized by a decrease of the uterine S/D, RI and PI values. There is a significant dependence between high values of S/D, RI, PI and observation of notch in uterine FVW at 20-24 weeks and development of PIH and IUGR in the course of pregnancy. Doppler velocimetry of the uterine blood flow as a screening method at 20-24 weeks allows to get a prognosis about further course of pregnancy in the groups of low- and high-risk for PIH and IUGR development.


Treatment of pediatric refractory coccidioidomycosis with combination voriconazole and caspofungin: a retrospective case series.
Coccidioidomycosis is a spectrum of diseases caused by the dimorphic fungi Coccidioides. Current regimens for severe or disseminated disease include fluconazole, itraconazole, or amphotericin; newer triazoles (ie, voriconazole, posaconazole) have been demonstrated to be useful in refractory disease. Previous reported experience with combination triazole and caspofungin therapy has been very limited; however, the utility of this combination for treatment of other invasive fungal diseases suggests potential benefit in refractory coccidioidomycosis. We conducted a retrospective review of 9 pediatric patients treated with combination voriconazole and caspofungin (V/C) salvage therapy for refractory coccidioidomycosis at two children's hospitals between January 2000 and June 2012. Nine children with refractory coccidioidomycosis were treated with V/C salvage therapy after failing conventional therapy consisting of a triazole, amphotericin B, or a combination of both. Eight of the 9 patients are currently in remission; 1 patient with central nervous system involvement continues to progress. We report our positive clinical experience treating medically refractory coccidioidomycosis in the pediatric population with concurrent voriconazole and caspofungin therapy. Additional in vitro and in vivo evaluations are warranted to support the role of V/C salvage therapy for refractory coccidioidomycosis.


Cardiomyopathies due to homoplasmic mitochondrial tRNA mutations: morphologic and molecular features.
Isolated hypertrophic cardiomyopathy may represent the sole clinical feature of a mitochondrial disorder in adult patients. The clinical outcome is characterized by a rapid progression to dilation and failure. A mitochondrial etiology in these cases is not obvious at clinical investigation and may represent an unexpected finding at autopsy or after cardiac transplant. We describe the morphologic, biochemical, and molecular features of hearts from 3 transplanted patients with isolated mitochondrial cardiomyopathy caused by homoplasmic mutations in the MTTI gene, coding for mitochondrial isoleucine tRNA (mt-tRNA(Ile)). On gross examination, the 3 hearts showed a symmetric pattern of hypertrophy. At histology, cardiomyocytes were hypertrophic and showed sarcoplasmic vacuoles filled with granules that stain with antimitochondrial antibodies. On frozen sections, the combined cytochrome c oxidase (COX)/succinate dehydrogenase stain showed a large prevalence of COX-deficient cardiomyocytes. Mitochondrially encoded COX subunit I was almost absent on immunohistochemistry, whereas the nuclear-encoded COX subunit IV was normally expressed. Ultrastructural analysis confirmed the marked mitochondrial proliferation. Biochemical studies of cardiac homogenates revealed a combined respiratory chain defect. Quantitative restriction fragment length polymorphism analysis of DNA from cardiac homogenate confirmed that the mt-tRNA mutations were also detected in the patient's blood. High-resolution Northern blot analysis showed a marked decrease in the steady-state level of mt-tRNA(Ile), confirming pathogenicity. In conclusion, pathologists play a major role in unraveling the mitochondrial etiology of isolated hypertrophic cardiomyopathies, provided that a detailed diagnostic flowchart is followed. Once the mitochondrial etiology is clearly defined, molecular analyses on the heart are an invaluable tool to assign mutation pathogenicity.


Induction of p16INK4a transcription and of cellular senescence by aclacinomycin-derivatives and cardiac glycosides.
Stable transformants of Saos-2 cells that contain the luciferase reporter gene under the control of the human p16INK4a transcriptional regulatory region were established, and were used to identify growth-inhibiting substances from culture broths of actinomycetes and extracts of plants. Among the active substances so far identified were an aclacinomycin-derivative, cenerubin B, and a cardiac glycoside, periplocin. These substances inhibited growth of normal human fibroblasts, and induced senescent phenotypes including a flattened morphology and increased acidic beta-galactosidase activity, although the activities of their derivatives to induce p16CDKN2 and beta-galactosidase did not coincided with each other. These results suggest that the reporter system using the p16CDKN2 transcriptional regulatory region is a useful means for screening growth inhibiting substances that are potential anti-tumor agents.


Smear layer removal efficacy of different irrigating solutions: a comparative scanning electron microscope evaluation.
Comparative evaluation of cleaning efficacy of smear layer removal by different irrigating solutions such as 2.5% sodium hypochlorite (NaOCl), 17% ethylenediaminetetraacetic acid (EDTA) with 2.5% NaOCl, 10% citric acid with 2.5% NaOCl and 1% tetracycline Hydrochloride (HCl) with 2.5% NaOCl for smear layer removal in the apical third of root canal. In vitro material science study. Seventy-five single rooted permanent maxillary central incisor teeth were subjected to standardized root canal instrumentation (crown down technique). The teeth were randomly divided into five groups with 15 teeth in each groups: (1) Normal saline (n = 15) (2) 2.5% NaOCl (n = 15) (3) 17% EDTA + 2.5% NaOCl (n = 15) (4) 10% citric acid + 2.5% NaOCl (n = 15) (5) 1.0% tetracycline HCL + 2.5% NaOCl (n = 15). After final irrigation, the teeth were prepared for scanning electron microscope analysis to evaluate the cleaning of apical third of radicular dentine to determine the presence or absence of smear layer. The results were analyzed by nonparametric statistical analysis techniques. Kruskal-Wallis test, Mann-Whitney test and Chi-square tests were carried out. There was no significant statistical difference in the efficacy of smear layer removal when 2.5% NaOCl was compared with 17% EDTA with 2.5% NaOCl, 10% citric acid with 2.5% NaOCl and 1% tetracycline HCl with 2.5% NaOCl in apical third of root canals. The present study suggests that irrigating agents, citric acid and tetracycline HCl can be used as an alternative to EDTA for the removal of smear layer in endodontics.


A lifestyle management programme focused on exercise, diet and physiotherapy support for patients with hip or knee osteoarthritis and a body mass index over 35: A qualitative study.
The Lifestyle Management Programme (LMP) is an exercise and weight management programme with physiotherapy support for people with hip or knee osteoarthritis (OA) and a body mass index (BMI) over 35. This qualitative study explored views and experiences of the LMP among patients and professionals, and offers insight for future programmes. Five referring clinicians and six delivering professionals participated in focus groups. Three referring GPs and nine patients who attended the LMP took part in semi-structured interviews. Topics included: referral, reasons for taking up and continuing the programme or not, and experiences and outcomes. Framework method was used to analyse the qualitative data. Overall, patients and professionals valued the multidisciplinary nature of the LMP. However, professionals explained feeling guilty about delaying patients on the orthopaedic waiting list and believed that the programme should be redirected to those with less severe OA and a lower BMI. Referring clinicians differed in their interpretation of the referral criteria and expressed varying levels of autonomy when making referrals. Patients referred after a consultation with their general practitioner appeared to be more satisfied with the referral process. Patients were also encouraged by the opportunity to improve health, their likelihood of surgery and social benefits. However, patients were discouraged by inconvenience, cost, lack of readiness to change and embarrassment. In conclusion, shared decision-making about lifestyle management without delaying orthopaedic opinion is preferable, and more psychological support may increase participation. Importantly, the programme may be better focused on rehabilitation for patients with a lower BMI and less severe symptoms.


In-patient Expenditure Between 2012 and 2020 Concerning Patients With Liver Cirrhosis in Chongqing: A Hospital-Based Multicenter Retrospective Study.
Liver cirrhosis is a major global health and economic challenge, placing a heavy economic burden on patients, families, and society. This study aimed to investigate medical expenditure trends in patients with liver cirrhosis and assess the drivers for such medical expenditure among patients with liver cirrhosis. Medical expenditure data concerning patients with liver cirrhosis was collected in six tertiary hospitals in Chongqing, China, from 2012 to 2020. Trends in medical expenses over time and trends according to subgroups were described, and medical expenditure compositions were analyzed. A multiple linear regression model was constructed to evaluate the factors influencing medical expenditure. All expenditure data were reported in Chinese Yuan (CNY), based on the 2020 value, and adjusted using the year-specific health care consumer price index for Chongqing. Medical expenditure for 7,095 patients was assessed. The average medical expenditure per patient was 16,177 CNY. An upward trend in medical expenditure was observed in almost all patient subgroups. Drug expenses were the largest contributor to medical expenditure in 2020. A multiple linear regression model showed that insurance type, sex, age at diagnosis, marital status, length of stay, smoking status, drinking status, number of complications, autoimmune liver disease, and the age-adjusted Charlson comorbidity index score were significantly related to medical expenditure. Conservative estimates suggest that the medical expenditure of patients with liver cirrhosis increased significantly from 2012 to 2020. Therefore, it is necessary to formulate targeted measures to reduce the personal burden on patients with liver cirrhosis.


Poor recognition of O6-isopropyl dG by MGMT triggers double strand break-mediated cell death and micronucleus induction in FANC-deficient cells.
Isopropyl methanesulfonate (IPMS) is the most potent genotoxic compound among methanesulfonic acid esters. The genotoxic potential of alkyl sulfonate esters is believed to be due to their alkylating ability of the O6 position of guanine. Understanding the primary repair pathway activated in response to IPMS-induced DNA damage is important to profile the genotoxic potential of IPMS. In the present study, both chicken DT40 and human TK6 cell-based DNA damage response (DDR) assays revealed that dysfunction of the FANC pathway resulted in higher sensitivity to IPMS compared to EMS or MMS. O6-alkyl dG is primarily repaired by methyl guanine methyltransferase (MGMT), while isopropyl dG is less likely to be a substrate for MGMT. Comparison of the cytotoxic potential of IPMS and its isomer n-propyl methanesulfonate (nPMS) revealed that the isopropyl moiety avoids recognition by MGMT and leads to higher cytotoxicity. Next, the micronucleus (MN) assay showed that FANC deficiency increases the sensitivity of DT40 cells to MN induction by IPMS. Pretreatment with O6-benzyl guanine (OBG), an inhibitor of MGMT, increased the MN frequency in DT40 cells treated with nPMS, but not IPMS. Lastly, IPMS induced more double strand breaks in FANC-deficient cells compared to wild-type cells in a time-dependent manner. All together, these results suggest that IPMS-derived O6-isopropyl dG escapes recognition by MGMT, and the unrepaired DNA damage leads to double strand breaks, resulting in MN induction. FANC, therefore, plays a pivotal role in preventing MN induction and cell death caused by IPMS.


Inflation and rupture of vaginal tissue.
Around 80% of women experience vaginal tears during labour when the diameter of the vagina must increase to allow the passage of a full-term baby. Current techniques for evaluating vaginal tears are qualitative and often lead to an incorrect diagnosis and inadequate treatment, severely compromising the quality of life of women. In order to characterize the failure properties of the vaginal tissue, whole vaginal tracts from rats (n = 18) were subjected to free-extension inflation tests until rupture using a custom-built experimental set-up. The resulting deformations were measured using the digital image correlation technique. Overall, the strain and changes in curvature in the hoop direction were significantly larger relative to the axial direction. At a failure pressure of 110 ± 23 kPa (mean ± s.d.), the hoop and axial stresses were computed to be 970 ± 340 kPa and 490 ± 170 kPa, respectively. Moreover, at such pressure, the hoop and axial strains were found to be 12.8 ± 4.4 % and 6.4 ± 3.7 % , respectively. Rupture of the vaginal specimens always occurred in the hoop direction by tearing along the axial direction. This knowledge about the rupture properties of the vaginal tissue will be crucial for the development of clinical approaches for preventing and mitigating vaginal tearing and the associated short- and long-term traumatic conditions.


Structural analyses of high-pressure and high-temperature treated double-walled carbon nanotubes.
This paper reports the structural properties of the high-pressure and high-temperature (HPHT) treated double-walled carbon nanotubes (DWCNTs) based on Raman, XRD and TEM experiments. It was found that the DWCNTs are more stable toward HPHT treatment than the single-walled carbon nanotubes (SWCNTs). We propose that this is probably because the DWCNTs tend not to be deformed by compression and thereby they are less reactive under pressure compared to SWCNTs.


[Treatment of femoral periprosthetic fracture of Vancouver type B1 and C with bridge combined internal fixation system].
To evaluate the clinical effect of bridge combined internal fixation system in the treatment of periprosthesis fracture of femur after hip replacement. From October 2016 to June 2018, 5 patients of periprosthesis fractures of femur classified type B1 and type C in Vancouver were treated by open reduction and bridging combined with internal fixation, including 2 males and 3 females, with ages of 68, 70, 74, 75, 79 years;type B1 fractures in 4 and type C fractures in 1. Causes of injury:1 case of traffic injury, 4 cases of fall. After the operation, the patients were followed up for complications and fracture healing time by clinical and imaging examination, and Parker activity score was performed. The wounds of 5 patients healed without infection. One case of DVT was confirmed by venography. Five patients were followed up, and the durations were 2, 8, 9, 10, 15 months. One patient died of myocardial infarction 2 months after operation. The average healing time was 12.5 weeks. No loss of reduction or failure of internal fixation was found. Two patients could walk without protection and 1 patient needed to rely on single crutch. One case of periprosthetic fracture had to walk with a single crutch before operation and move indoors with two crutches after operation. The average Parker activity score was 51.8% before operation. The bridge combined internal fixation system can be used to fix the fracture after hip replacement with stable femoral prosthesis.


The apolipoprotein m-sphingosine-1-phosphate axis: biological relevance in lipoprotein metabolism, lipid disorders and atherosclerosis.
Apolipoprotein M (apoM) is a plasma apolipoprotein that mainly associates with high-density lipoproteins. Hence, most studies on apoM so far have investigated its effect on and association with lipid metabolism and atherosclerosis. The insight into apoM biology recently took a major turn. ApoM was identified as a carrier of the bioactive lipid sphingosine-1-phosphate (S1P). S1P activates five different G-protein-coupled receptors, known as the S1P-receptors 1-5 and, hence, affects a wide range of biological processes, such as lymphocyte trafficking, angiogenesis, wound repair and even virus suppression and cancer. The ability of apoM to bind S1P is due to a lipophilic binding pocket within the lipocalin structure of the apoM molecule. Mice overexpressing apoM have increased plasma S1P concentrations, whereas apoM-deficient mice have decreased S1P levels. ApoM-S1P is able to activate the S1P-receptor-1, affecting the function of endothelial cells, and apoM-deficient mice display impaired endothelial permeability in the lung. This review will focus on the putative biological roles of the new apoM-S1P axis in relation to lipoprotein metabolism, lipid disorders and atherosclerosis.


Management of tear trough deformity with and without tear trough-orbicularis retaining ligament complex release in transconjunctival blepharoplasty: a comparative study.
To evaluate the effect of releasing the orbicularis retaining ligament (ORL) complex of the tear trough combined with the transconjunctival blepharoplasty in the surgical management of tear trough deformity compared with the effect of blepharoplasty alone. A prospective, randomized (by closed envelope technique), controlled surgical trial which included 50 patients (100 eyes) with bilateral visible tear trough deformity and lower eyelid fat bulging, was divided into two groups where 25 patients (50 eyes) had tear trough-ORL release with blepharoplasty and 25 patients (50 eyes) didn't. Qualitative and quantitative assessments of tear trough deformity were done at 6mo postoperatively, achieving grade 0 or 1 of Barton's classification was considered a success. Standardized photographic documentation of each patient was done pre and postoperatively, also assessment of the patients' satisfaction postoperatively was done and ranked as excellent, very good, good or fair. There was statistically significant difference between the two groups in the overall aesthetic results postoperatively regarding the qualitative and quantitative analysis of the tear trough deformity, where patients who had tear trough-ORL complex release had more successful outcomes than those of the second group. ORL release should be done in patients with tear trough deformity in order to release the tethering effect of this ligament which causes the prominence of the naso jugal groove.


MCP-1-induced migration of NT2 neuroprogenitor cells involving APP signaling.
Neuroprogenitor cells are an important resource because of their great potential to replace damaged cells in the brain caused by trauma and disease. Studies have shown that when neuroprogenitor cells are transplanted into the brain they migrate towards damaged areas, suggesting that these areas express factors that recruit migrating cells. Generally, after neuronal injury, there is a neuroinflammatory response that results in increased chemokine production. In this present study, we demonstrate that monocyte chemoattractant protein-1 (MCP-1) significantly induces the migration of NT2 neuroprogenitor cells. Activation of intracellular cyclic adenosine monophosphate or protein kinase C with forskolin and phorbol 12-myristate 13-acetate, respectively, was able to completely abolish the MCP-1-induced migration. Contrarily, neither extracellular signal-regulated kinase nor p38 mitogen-activated protein kinase was required for NT2 cells to respond to MCP-1. Previously, we showed that amyloid precursor protein (APP) activity increases MCP-1 expression in NT2 cells. We now demonstrate that NT2 cells expressing APP can induce migration of other neuroprogenitor cells. Utilizing a MCP-1 neutralizing antibody, we discovered that APP-induced migration was not caused solely by increased MCP-1 production. Interestingly, APP-increased expression of several C-C chemokines: MCP-1, regulated upon activation, normal T-cell expressed, and secreted (RANTES), and macrophage inflammatory protein alpha (MIP-1 alpha). This demonstrates the unique role APP has in regulating chemokine production, which directly affects cell migration. Taken together, these data provides greater detail of the chemotactic factors and intracellular signaling that direct neuroprogenitor cell migration, allowing for better understanding of cell migration during transplantation.


Using Markov processes to describe the prognosis of HIV-1 infection.
In 1989, Turner and colleagues proposed a new method for automated classification and prediction of outcomes for hospitalized patients with AIDS, based on severity of illness. The authors have confirmed this system, which includes three main stages and 20 substages, in a cohort of HIV-1-infected symptomatic patients admitted to the Miami Veteran's Affairs Medical Center (VAMC) since 1988. They propose a new model of Markov illness-and-death processes and use it to describe the disease progression of the patient cohort. The new Markov model also measures transitions between stages, including risk factors associated with the speed of transitions. Significant differences in survival experiences were found from the different disease stages. The estimated mean (median) survival times were: from stage 1, 21.0 (17.8) months; from stage 2, 10.5 (8.4) months; and from stage 3, 6.7 (4.7) months. In addition, age at HIV-1 diagnosis and homosexual behavior were significant prognostic factors for disease progression and survival. The results indicate that the combination of a severity-of-illness clinical staging system with Markov illness-and-death process modeling is particularly useful for the evaluation of prognostic factors influencing the course of HIV-1 disease progression.


Cell signaling promoting protein carbonylation does not cause sulfhydryl oxidation: Implications to the mechanism of redox signaling.
Reactive oxygen species (ROS) have been recognized as second messengers, however, targeting mechanisms for ROS in cell signaling have not been defined. While ROS oxidizing protein cysteine thiols has been the most popular proposed mechanism, our laboratory proposed that ligand/receptor-mediated cell signaling involves protein carbonylation. Peroxiredoxin-6 (Prx6) is one protein that is carbonylated at 10 min after the platelet-derived growth factor (PDGF) stimulation of human pulmonary artery smooth muscle cells. In the present study, the SulfoBiotics Protein Redox State Monitoring Kit Plus (Dojindo Molecular Technologies) was used to test if cysteine residues of Prx6 are oxidized in response to the PDGF stimulation. Human Prx6 has a molecular weight of 25 kDa and contains two cysteine residues. The Dojindo system adds the 15 kDa Protein-SHifter if these cysteine residues are reduced in the cells. Results showed that, in untreated cells, the Prx6 molecule predominantly exhibited the 55 kDa band, indicating that both cysteine residues are reduced in the cells. Treatment of cells with 1 mM H 2O 2 caused the disappearance of the 55 kDa band and the appearance of a 40 kDa band, suggesting that the high concentration of H 2O 2 oxidized one of the two cysteine residues in the Prx6 molecule. By contrast, PDGF stimulation had no effects on the thiol status of the Prx6 molecule. We concluded that protein carbonylation is a more sensitive target of ROS during ligand/receptor-mediated cell signaling than sulfhydryl oxidation.


The effects of tool holding on body schema during motor imagery: a near-infrared spectroscopy study.
[Purpose] The purpose of this study is to assess the influence of tool holding on brain activities during motor imagery in two tasks: imagining the movement of writing the alphabet while holding a pen and without holding the pen. [Subjects and Methods] Eleven healthy right-handed adults performed two tasks, holding a pen and not holding the pen during imagining the movement of writing the alphabet using a pen. Regions of targets were Brodmann areas 6 which were a motor-related region, 44/45 and 39/40 which taken on the role of forming the body schema. Change of the oxygenation state of hemoglobin associated with brain activity were acquired using a near-infrared spectroscopy. [Results] When using their dominant right hands, task-related increases in oxy-Hb were prominent in Brodmann areas 44/45 and 39/40 when imagining writing while actually holding the pen than when not. When using the non-dominant left hands, there were no significant differences between the two conditions in the same areas. [Conclusion] These results suggest that the tool held can be incorporated into the body schema in the motor imagery of an automated tool use task. Therefore, tool holding during motor imagery might be more effectively influence during rehabilitation.


Infusion of DDAVP does not improve primary hemostasis in patients with cirrhosis.
Cirrhosis frequently affects multiple components of hemostasis. Reversal of the coagulopathy of these patients is frequently required in case of bleeding episodes, or as prophylaxis before invasive procedures. Although 1-deamino-8-D-arginine vasopressin (DDAVP) is widely used as a pro-hemostatic agent in patients with cirrhosis, it is unclear whether DDAVP truly enhances hemostasis in these patients. Here we investigated the hemostatic effects of a single bolus of DDAVP in patients with cirrhosis. Ten patients with cirrhosis (child B or C) and ten patients with mild haemophilia A received an intravenous single bolus of 0.3 microgram/kg DDAVP. Plasma was collected prior to and at 1, 3, 6, and 24 h after DDAVP administration. Levels of Von Willebrand factor (VWF), VWF propeptide, factor VIII (FVIII), and ADAMTS13 were measured in all plasma samples, whereas VWF multimers and functional VWF-dependent platelet adhesion were determined in the samples pre- and 1 h after DDAVP administration. Following DDAVP administration, VWF, FVIII, and VWF propeptide levels increased in patients with haemophilia, while patients with cirrhosis only showed an increase in VWF propeptide and FVIII levels. High molecular weight VWF multimers and VWF-dependent platelet adhesion increased in patients with haemophilia one hour after DDAVP administration, but did not change in the patients with cirrhosis. Levels of ADAMTS13 were unaffected in both patient groups after DDAVP. The lack of relevant effects of DDAVP on laboratory indices of primary hemostasis in patients with cirrhosis is in line with previous clinical study results in these patients.


In vitro susceptibility of Pseudomanas cepacia and Pseudomonas maltophilia to trimethoprim and trimethoprim-sulfamethoxazole.
Our earlier studies had shown that the two pseudomonads, Pseudomonas cepacia and Pseudomonas maltophilia, were organisms that were highly resistant to most antibiotics. The present study was undertaken to determine the susceptibility of these bacteria to trimethoprim and the trimethoprim-sulfamethoxazole combination which has been used with apparent success in treating infections caused by these pseudomonads. All 51 strains of P. cepacia were inhibited by 2 mug or less of trimethoprim per ml, whereas all 45 of the P. maltophilia were resistant to greater than 32 mug/ml. When the P. maltophilia was tested against trimethoprim-sulfamethoxazole, two strains were resistant and one only moderately resistant, but all other strains were susceptible. All P. cepacia strains were also susceptible with an average zone of inhibition significantly larger than for P. maltophilia (P < 0.005). These in vitro studies support recent case study reports of successful therapy using the trimethoprim-sulfamethoxazole combination.


In the prevention of dementia, the focus should be on early and consistent treatment of hypertension.
The brain is among the target organs of hypertension. Patients with hypertension have a higher risk of developing stroke as well as experiencing a decline in cognitive functions and dementia. Changes in the white matter and atrophy of the grey matter of the brain induced by high blood pressure develop insidiously since the onset of hypertension, even in young individuals. The effect of high blood pressure on the vessel wall cumulates in time; therefore, hypertension in younger people implies an increased risk of dementia in older age. Hypertension in young age cannot be considered a benign condition. Hypertension in middle age increases the risk of dementia by 61 %. Consistent and early hypertension control can reverse the adverse development towards dementia and lack of self-sufficiency in the patient. Data comparing individual antihypertensive drugs in terms of preventing dementia are scarce. However, renin angiotensin system blockers have been found to protect against Alzheimer's disease more than other classes of antihypertensive drugs. To achieve rapid and effective hypertension control, a combination of antihypertensive drugs is usually required. Using a fixed-dose triple combination of perindopril, indapamide, and amlodipine, blood pressure targets of < 130/80 mm Hg can be achieved within three months in 93 % of patients.


The Relationship between Risk Factors of Head Trauma with CT Scan Findings in Children with Minor Head Trauma Admitted to Hospital.
In emergency medicine for determining the intracranial injury (ICI) in children with head trauma, usually brain CT scan is performed. Since brain CT scan, especially in children, has some disadvantages, it is better to find a procedure which could help to choose only the children with real head trauma injury for brain CT scan. The aim of this study is to find such procedure. This study was descriptive, analytic and non-interventional. We reviewed the archived files of children with head trauma injuries referred to the emergency department of Imam Hossein Hospital within two years. Patient's CT scan findings and head trauma risk factors were evaluated in this study. Out of 368 patients, 326 patients had normal brain CT scan. 28 of them showed symptoms of ICI consisting intraventricular haemorrhage (IVH), contusion, subarachnoid haemorrhage (SAH), subdural haemorrhage (SDH), epidural hematoma (EDH), and pneumocephalus. Twenty-seven patients showed skull FX, which 14 of them had an Isolated fracture, and 13 of them also showed symptoms of ICI. Since patients with isolated FX usually discharge quickly from Emergency Department; their data did not include in results of the study. The patients have been divided into two groups: 1- ICI, 2- without ICI. RR (relative risk), CI (Confidence interval) and sensitivity, positive predictive value (PPV), negative predictive value (NPV) and association of these risk factors with ICI were assessed with the Chi-2 test. In the end to determine the indications of CT scan, the presence of one of these five risk factors is important including abnormal mental status, clinical symptoms of skull FX, history of vomiting, craniofacial soft tissue injury (including subgaleal hematomas or laceration) and headache. For all other patients without these risk factors, observation and Follow Up can be used which has more advantages and less cost.


Inhibition of gelatinase B/MMP-9 does not attenuate colitis in murine models of inflammatory bowel disease.
One third of patients with inflammatory bowel disease (IBD) inadequately respond to anti-TNF treatment and preclinical data suggest that matrix metalloproteinase-9 (MMP-9) is a novel therapeutic target. Here we show that IBD clinical and histopathological parameters found in wild type mice challenged with three different models of colitis, acute and chronic dextran sodium sulphate (DSS), and acute 2,4,6-trinitrobenzenesulfonic acid-induced colitis are not attenuated in MMP-9 knockout mice. We find similar colonic gene expression profiles in wild type and MMP-9 knockout mice in control and acute DSS conditions with the exception of eleven genes involved in antimicrobial response during colitis. Parameters of chronic colitis are similar in wild type and MMP-9 knockout mice. Pharmacological inhibition of MMP-9 with bio-active peptides does not improve DSS colitis. We suggest that MMP-9 upregulation is a consequence rather than a cause of intestinal inflammation and we question whether MMP-9 represents a disease target in IBD.


Nutrient starvation affects expression of LC3 family at the feto-maternal interface during murine placentation.
LC3 - the mammalian homolog of Atg8 - was found as autophagosome membrane binding protein in mammals and widely used as an autophagosomal marker. LC3A, B and C show different expression patterns in each tissue. The aim of this study was to reveal the differences of expression patterns among LC3 families in mouse placenta under normal condition and nutrient starving condition. LC3A and B were highly expressed in decidual cells. LC3A and B were increased in D14 compared with D12 and D16 in mouse placenta, while LC3C was decreased. Starvation induced increase in LC3B expression specifically. Immunohistochemistry showed different expression patterns among LC3A, B and C. LC3A expression in syncytiotrophoblast was vanished by starvation. The results of real time RT-PCR suggested differences between D12 and D16 in autophagic cascade induced by starvation. Taken together, this study suggests that autophagy could play a role in placental invasion system and that nutrient starvation affects LC3B expression.


Effects of caerulein and trypsin inhibitors on the endocrine mouse pancreas.
Oral administration to mice with soybean trypsin inhibitor (SBTI) (27-30 mg/mouse/day) or aprotinin (5500-6000 KIU/mouse/day) for six weeks increased the total pancreatic insulin (IRI). The pancreatic IRI was also increased after sc injections of synthetic caerulein (0.05 microgram/mouse/day divided into 3 daily doses), being 82% above the control levels when expressed per g pancreas. Aprotinin (6000 KIU/mouse/day divided into 3 daily doses) injected sc had no effect on the insulin content. The total glucagon did not change significantly in any of the groups, but the molar ratio of insulin to glucagon was increased in the caerulein- and SBTI-treated mice. Caerulein-treatment led to an increased disappearance rate of glucose with k-values being 7.1 +/- 0.3 compared to 6.0 +/- 0.1 (mean +/- SEM) in the controls (P less than 0.02). In islets isolated by collagenase-digestion of the pancreas and subjected to an overnight incubation, the content of insulin and glucagon was increased in islets from caerulein-treated animals. This corresponded to the results observed in the whole pancreas. The present study suggests that oral administration of proteolytic enzyme inhibitors or treatment with caerulein has a trophic effect on the endocrine pancreas. A difference in specificity seems to exist as SBTI affected both the pancreatic weight and IRI, and aprotinin orally did not influence the pancreatic weight, but increased the total content of IRI. Caerulein led to an increase in IRI, but did not affect the weight of pancreas.


Further characterization of the cation channel of a yeast vacuolar membrane in a planar lipid bilayer.
A voltage-dependent and Ca2(+)-activated cation channel recently found in the vacuolar membrane of the yeast Saccharomyces cerevisiae was incorporated into planar lipid bilayers and further characterized in macroscopic and single channel levels. Single channel conductances for various cations were in the order: NH4+ greater than K+ greater than Rb+ greater than Cs+ greater than Na+ greater than Li+, and were nearly consistent with the order of permeability ratio estimated from reversal potentials determined by macroscopic measurement. Up to 6 mM of Ca2+ added to the cis (cytoplasmic) side opened the channel, but higher concentrations closed the channel without affecting the single channel conductance. Ba2+ closed the channel without affecting the single channel conductance. Ba2+ closed the channel from the cis side. In addition to the above channel, a small cation-selective channel of about 40 pS was found.


Current regimen of pulse therapy for pemphigus: minor modifications, improved results.
If administered properly, dexamethasone cyclophosphamide pulse (DCP) therapy has the potential to effect lifelong recovery from pemphigus. The objective of this paper is to highlight various parameters of DCP therapy and also, to report the effects of a few modifications in the regimen. An analysis of 123 patients treated with the DCP/DP regimen over a period of five years (1998 to 2002) is presented here. Seventeen patients who did not start/continue the treatment and three patients who died during the treatment have been excluded from the analysis. Twenty patients who had not yet started families were given only dexamethasone pulses (DPs) while 103 patients received DCPs. Low dose (50 mg/day) cyclophosphamide was used as in the standard regimen. The three modifications introduced into the regimen were: (1) an additional daily dose of oral betamethasone sufficient to control the disease activity during phase I, which was progressively tapered off completely as the patient recovered, (2) use of systemic antibiotics if the patient had skin lesions, and oral anti-candida drugs if the patient had oral ulcers until complete healing, and (3) insistence on thorough cleaning of the skin and scalp with a normal soap and shampoo, and proper maintenance of oral hygiene in spite of skin/mucosal lesions. The regimen consisted of DCP/DP repeated in exactly 28-day cycles, along with 50 mg cyclophosphamide per day, insistence on completing the treatment and avoiding irregular pulses in all patients. The number of DCPs/DPs during phase I varied in different patients depending upon the dose of betamethasone used and the rate of recovery, but phase II (nine DCPs/DPs in exactly 28-day cycles along with 50 mg cyclophosphamide per day) and phase III (only 50 mg cyclophosphamide per day) was fixed at nine months each. This was followed by posttreatment follow-up (phase IV). At present, all the patients are in complete remission. The confirmed period of posttreatment, disease-free follow-up period has already been more than five years in 62 patients, 3-5 years in 41 patients, 2-3 years in three patients and less than two years in six patients. Eight DCP patients and three DP patients developed a relapse (the relapse rates thus being 7.7 and 15% respectively) and received a second course of pulse therapy. They are also in remission at present. The duration of phase I was three months in 62 patients, 4-5 months in 28 patients, 6-9 months in 13, 10-12 months in nine patients and more than 12 months in 11 patients. The maximum daily dose of betamethasone used in these patients was nil in 17 patients, 1-2 mg in 85, 3-4 mg in 16, and> 4 mg in five patients. The modifications employed in this study could ensure the cure of all pemphigus patients by using DCP therapy administered at a private clinic.


Evaluation of the relationship between splenic iron overload and liver, heart and muscle features evident on T2*-weighted magnetic resonance imaging.
Splenic iron overload is the most common clinical condition in patients with thalassemia. However, few studies of the effects of splenectomy have been published. To evaluate the relationship between splenic iron overload and liver, heart and muscle features visible in T2*-weighted magnetic resonance imaging, and to investigate the effects of splenectomy on these tissues in patients with beta-thalassemia major (TM). We retrospectively included 131 patients (76 male and 55 female) diagnosed with TM. All radiological assessments were performed with the aid of a Philips Achieva 1.5T scanner running a multiecho gradient-echo sequence. Hepatic and splenic T2* values were assessed in the same gradient multiecho series. Muscle T2* values were assessed in the shoulder girdle muscles adjacent to the heart area. The relationships among splenic T2*, hepatic T2*, cardiac T2* and muscle T2* parameters, serum ferritin levels, age and other parameters were evaluated. The splenic T2* value correlated with serum ferritin level and the hepatic T2* value (p < 0.001 and p < 0.001, respectively). The splenic T2* value did not correlate with age, cardiac or muscle T2* values, or with spleen size (p = 0.27, 0.21, 0.99, and 0.39, respectively). The muscle T2* value correlated weakly with the serum ferritin level (p = 0.022). The cardiac T2* value was lower and the liver size greater in patients who had undergone splenectomy compared with those who had not (p < 0.001 and 0.001, respectively). Splenic iron overload correlated with hepatic overload and the serum ferritin level. Splenectomy increased cardiac iron overload and triggered liver enlargement. However, the muscle iron overload was low and the muscles were therefore unaffected by splenectomy.


Collapsing glomerulopathy--a new pattern of renal injury.
Collapsing glomerulopathy is a pattern of renal injury that has emerged along with the epidemic of HIV infection. The disease process is now increasingly recognized in non-HIV patients. In HIV and non-HIV patients the disease shares many clinical and pathologic features, and, we presume, pathogenetic factors. The disease entity is characterized by very heavy proteinuria frequently combined with rapidly progressive renal failure, poor outcome, glomerular collapse with hyperplasia and other degenerative changes of the visceral epithelial cells, and prominent tubulointerstitial injury with frequent microcystic changes. HIV-associated nephropathy has a higher prevalence in blacks, high frequency of intra-endothelial tubuloreticular inclusions, and prominent microcystic tubular changes. These differences, however, are not sufficient to predict the patient's HIV status from the biopsy findings alone. Collapsing glomerulopathy can also develop in association with lymphoproliferative disorders, systemic lupus erythematosus-like and other autoimmune diseases, other immune deficiency syndromes and viral infections, and in the context of immunosuppressive therapy.


Disentangling Origins of Adhesive Bonding at Interfaces between Epoxy/Amine Adhesive and Aluminum.
Joining metals by adhesive bonding is essential in widespread fields such as mobility, dentistry, and electronics. Although adhesive technology has grown since the 1920s, the roles of interfacial phenomena in adhesive bonding are still elusive, which hampers the on-demand selection of surface treatment and adhesive types. In the present study, we clarified how chemical interactions and mechanical interlocking governed adhesive bonding by evaluating adhesion properties at the interfaces between epoxy/amine adhesive and two kinds of Al adherends: a flat aluminum hydroxide (AlxOyHz) and technical Al plate with roughness. Spectroscopic and microscopical data demonstrate that the protonation of the amino groups in an amine hardener converts Al(OH)3 on the AlxOyHz surface to AlO(OH). The interfacial protonation results in an interfacial dipole layer with positive charges on the adhesive side, whose electrostatic interaction increases the interfacial fracture energy. The double cantilever beam tests for the flat AlxOyHz and technical Al substrates clarify that the mechanical interlocking originating from the surface roughness further increases the fracture energy. This study disentangles the roles of the chemical interactions and mechanical interlocking occurring at the epoxy adhesive/Al interface in the adhesion mechanism.


Influence of nanohelical shape and periodicity on stem cell fate.
Microenvironments such as protein composition, physical features, geometry, and elasticity play important roles in stem cell lineage specification. The components of the extracellular matrix are known to subsequently assemble into fibrillar networks in vivo with defined periodicity. However, the effect of the most critical parameter, which involves the periodicity of these fibrillar networks, on the stem cell fate is not yet investigated. Here, we show the effect of synthetic fibrillar networks patterned with nanometric periodicities, using bottom-up approaches, on the response of stem cells. We have used helical organic nanoribbons based on self-assemblies of Gemini-type amphiphiles to access chiral silica nanoribbons with two different shapes and periodicities (twisted ribbons and helical ribbons) from the same native self-assembled organic nanostructure. We demonstrate the covalent grafting of these silica nanoribbons onto activated glass substrates and the influence of this programmed isotropically oriented matrix to direct the commitment of human mesenchymal stem cells (hMSCs) into osteoblast lineage in vitro, free of osteogenic-inducing media. The specific periodicity of 63 nm (±5 nm) with helical ribbon shape induces specific cell adhesion through the fibrillar focal adhesion formation and leads to stem cell commitment into osteoblast lineage. In contrast, the matrix of periodicity 100 nm (±15 nm) with twisted ribbon shape does not lead to osteoblast commitment. The inhibition of non-muscle myosin II with blebbistatin is sufficient to block this osteoblast commitment on helical nanoribbon matrix, demonstrating that stem cells interpret the nanohelical shape and periodicity environment physically. These results indicate that hMSCs could interpret nanohelical shape and periodicity in the same way they sense microenvironment elasticity. This provides a promising tool to promote hMSC osteogenic capacity, which can be exploited in a 3D scaffold for bone tissue engineering.


The Effectiveness of Psychoeducational Interventions in Reducing the Care Burden of Family Members Caring for the Elderly in Turkey: A Randomized Controlled Study.
To examine the effectiveness of psychoeducational intervention that is based on the McGill Model of Nursing in reducing the burden of caregivers and improving self-efficacy and adaptive coping in people who provide care for the older person. This study was conducted using a pre- and post-test control group and repeated measures experimental design in a family health center service area located in Istanbul. This study was conducted with 33 caregivers in each group. The data were collected using the questionnaire form, the Zarit Burden Interview, the General Self-Efficacy Scale and the Cognitive Emotion Regulation Questionnaire. According to the findings of the study, the post-test Zarit Burden Interview points of the intervention group trained for according to McGill Model of Nursing will decrease compared with the control group after the intervention hypothesis was accepted; the post-test General Self-Efficacy Scale and adaptive subscales of the Cognitive Emotion Regulation Questionnaire scores will increase after the intervention hypothesis was also accepted. It was found that the psychoeducational intervention based on the McGill Nursing Model was efficient.


Keratin-positive epithelioid angiosarcoma of thyroid. A report of four cases.
We present four cases of a malignant thyroid tumor showing morphologic, immunocytochemical, and ultrastructural features of endothelial cell differentiation. The tumor cells had epithelioid features and displayed strong immunoreactivity for keratin. There was no evidence of follicular or C-cell differentiation in any instance. We interpreted these cases as keratin-positive epithelioid angiosarcomas. The findings presented here support the existence of primary malignant vascular tumors in the thyroid even in the presence of keratin positivity, a marker traditionally regarded as indicative of epithelial differentiation.


Instituting a routine varicella vaccination program in Canada: an economic evaluation.
After licensing of a varicella vaccine in Canada in 1998, Health Canada commissioned a study to evaluate options for a vaccination program. The evaluation of a program of vaccination of 12-month-old children, with and without a catch-up program for susceptible 12-year-olds, is presented here. An economic model was developed simulating the expected experience, with and without vaccination, of cohorts of children susceptible to varicella. The cohorts were simulated for 70 years, and infection and complication rates were calculated along with the attendant costs, with an assumed vaccine cost of $60. With an 85% coverage rate vaccination is expected to reduce the number of chickenpox cases by approximately two-thirds and varicella-related complications by up to 75%. The overall costs of varicella are expected to drop by >$4 million (1998 Canadian dollars) per 100,000 eligible vaccinees, but costs to the health care system are expected to increase by >$2 million. From the health care system perspective, vaccination would cost approximately $42 per discounted case avoided. Routine varicella vaccination would likely substantially reduce the overall costs of managing chickenpox but would result in an increase in health care expenditures. These findings are consistent with evaluations in other countries.


NH2-MIL-53(Al) nanocrystals: a fluorescent probe for the fast detection of aromatic nitro-compounds and ions in aqueous systems.
NH2-MIL-53(Al) nanocrystals were successfully fabricated by an improved solvothermal route at 120 °C for 24 h without the addition of any surfactants or capping agents, employing AlCl3·6H2O and 2-amino terephthalic acid (NH2-BDC) as the initial reactants, and N,N-dimethylformamide (DMF) and water with a volume ratio of 5/25 as the mixed solvent. The as-obtained product was characterized by XRD, FESEM and FTIR. Under the excitation of 380 nm UV light, the as-obtained NH2-MIL-53(Al) nanocrystals displayed strong fluorescence emission. It was found that some aromatic nitro-compounds (ANCs) or ions in aqueous systems could strongly quench the above fluorescence, indicating that the as-obtained NH2-MIL-53(Al) nanocrystals could be made into a fluorescent probe for the detection of ANCs and ions in aqueous systems. Simultaneously, the mechanism to cause fluorescence quenching was discussed.


A successful management of fungal peritonitis caused by Rhodotorula glutinis in CAPD patient, coincident with onychomycosis by Penicillium sp: Case report.
Rhodotorula glutinis is a rare cause of fungal peritonitis in peritoneal dialysis (PD) patients. The combination treatment between aggressive PD catheter replacement and adequate antifungal treatment is crucial in managing peritonitis due to fungal infection and onychomycosis. A 37-year-old man PD patient presented with cloudy effluent, abdominal pain, and black debris in the lumen of his PD catheter. Twelve days before admission, the patient traveled for 10 days to a high-temperature country, Saudi Arabia, for purpose of accomplishing haj. From the physical examinations, there was an onychomycosis in his right toenail. The result of the dialysate cell count confirmed the evidence of peritonitis (i.e., cell count of 187 cells per µL, however with polymorphonuclear 31%). The dialysate culture indicated R glutinis, with no growth of bacteria. Fungal culture of his toenail scrapings was obtained and the result was Penicillium sp. Based on the high clinical suspicion of fungal peritonitis, fluconazole intraperitoneal (IP) was immediately given on the first day in addition to empirical antibiotics, that is, cefazolin and gentamycin IP. His peritoneal catheter was simultaneously removed and reinserted on the 4th day of treatment. Since there was a sign of fluconazole resistance, fluconazole IP was switched into oral voriconazole, without any antimicrobial treatment intraperitoneally. After 21 days of voriconazole, oral itraconazole was given until 3 months for his onychomycosis. Clinical improvement was seen on the effluent where the leucocyte count falls below 100 cells after 21 days of giving voriconazole. This case report suggests the need for comprehensive evaluations of the risk for fungal infection in continuous ambulatory PD patients, especially those who live in a tropical country.


Open Versus Laparoscopic Repair of Traumatic Diaphragmatic Injury: A Nationwide Propensity-Matched Analysis.
Minimally invasive surgical techniques have become routinely applied in the evaluation and treatment of patients with isolated traumatic diaphragmatic injuries (TDI). However, there remains a paucity of data that compares the laparoscopic repair to the open repair approach. The aim of our study is to examine patient outcomes between TDI patients managed laparoscopically versus those managed using open repair. Adult (age ≥18 years) trauma patients presenting with TDI that required surgical repair were identified in the Trauma Quality Improvement Program database 2017. Patients were excluded if they underwent any other surgical procedure of the abdomen or chest. Patients were then stratified into 2 groups based on the surgical approach: laparoscopic repair of the diaphragm versus open repair. Propensity-score matching in a 1:2 ratio was performed. Primary outcome measures were in-hospital major complications and length of stay (LOS). Secondary outcome measure was in-hospital mortality. A total of 177 adult trauma patients who had a laparoscopic repair of their isolated diaphragmatic injury were matched to 354 patients who had an open repair. Mean age was 35 ± 16 years, 78% were male, and mean BMI was 27 ± 7 kg/m2. 67 percent of the patients had penetrating injuries, and the median ISS was 17 [9-21]. CT imaging was done in 67% of the patients, with 71% presenting with left-sided injury and 21% having visceral herniation. Conversion from laparoscopic to open was reported in 7.3% of the cases. Patients with a laparoscopic repair had significantly lower rates of major complications (5.6 versus 14.4%; P<0.001), shorter hospital LOS (6 [3-9] versus 9 [5-13] days; P<0.001) and ICU LOS (3 [2-7] versus 5 [2-10] days; P<0.001). No difference was found in rates of in-hospital mortality (0.6 versuss 2.0%; P = 0.129) between the 2 groups. Laparoscopic repair of traumatic diaphragmatic injury was associated with decreased morbidity and a shorter hospital course, with a low conversion rate to open repair. Future studies remain necessary to further explore the long-term outcomes of patients with such injury. Level III STUDY TYPE: Therapeutic.


Quasi-experimental study designs series-paper 11: supporting the production and use of health systems research syntheses that draw on quasi-experimental study designs.
To describe the infrastructure available to support the production of policy-relevant health systems research syntheses, particularly those incorporating quasi-experimental evidence, and the tools available to support the use of these syntheses. Literature review. The general challenges associated with the available infrastructure include their sporadic nature or limited coverage of issues and countries, whereas the specific ones related to policy-relevant syntheses of quasi-experimental evidence include the lack of mechanism to register synthesis titles and scoping review protocols, the limited number of groups preparing user-friendly summaries, and the difficulty of finding quasi-experimental studies for inclusion in rapid syntheses and research syntheses more generally. Although some new tools have emerged in recent years, such as guidance workbooks and citizen briefs and panels, challenges related to using available tools to support the use of policy-relevant syntheses of quasi-experimental evidence arise from such studies potentially being harder for policymakers and stakeholders to commission and understand. Policymakers, stakeholders, and researchers need to expand the coverage and institutionalize the use of the available infrastructure and tools to support the use of health system research syntheses containing quasi-experimental evidence.


Radial control of recognition and redox processes with multivalent nanoparticle hosts.
Mixed Monolayer Protected Gold Clusters (MMPCs) featuring both hydrogen bonding and aromatic stacking molecular recognition functionalities have been used to create multivalent hosts for flavins. Multitopic binding of these hosts to flavin was shown to have a strong radial dependence: when the recognition site was brought closer to the MMPC surface, recognition was enhanced approximately 3-fold due to increased preorganization. The effect of preorganization is reversed upon reduction of flavin, where the MMPC with longer side chains bind the flavin guest approximately 7-fold stronger than the short chain counterpart due to unfavorable dipolar interactions between the electron-rich aromatic stacking units of the host and the anionic flavin guest. This fine-tuning of recognition and redox processes provides both a model for enzymatic systems and a tool for the fabrication of devices.