Local anesthesia vs general anesthesia during endovascular therapy for acute posterior circulation stroke.
The optimal anesthetic approach during endovascular therapy (EVT) in acute stroke patients remains an area of uncertainty. We investigated the impact of different anesthetic approaches on the outcome of posterior circulation stroke (PCS) patients undergoing EVT. For this observational study, we enrolled consecutive PCS patients who underwent EVT from December 2012 to December 2018, and compared functional outcomes at 90 days as well as long-term follow-up in patients treated under local anesthesia (LA) versus general anesthesia (GA). Multivariable logistic regression and propensity score matched analyses were conducted. Among the 183 patients included in this study, 71 patients (38.8%) received LA and 112 patients (61.2%) received GA. Median modified Rankin Scale score at 90 days was 4 (IQR, 2-6) in both groups (P = .956). No significant differences in the rates of functional independence and mortality at 90 days as well as long-term follow-up post intervention were observed between the two groups, and Kaplan-Meier survival analysis showed comparable long-term survival probabilities. Safety outcomes (including procedure-related complications and serious adverse events) did not differ between these patients. The anesthetic approach was neither associated with functional independence nor associated with mortality. Propensity score matched analysis indicated similar results. For PCS patients undergoing EVT, LA compared with GA does not seem to result in different functional outcomes and complications rates.


Prevalence and clinical correlates of familial hypercholesterolemia founder mutations in the general population.
This study aimed to investigate the exact prevalence of familial hypercholesterolemia (FH) in the general population, taking advantage of the fact that five low-density lipoprotein receptor (LDLR) founder mutations account for 78% of FH cases in Finland. Five LDLR founder mutations, FH-North Karelia, FH-Helsinki, FH-Pogosta, FH-Turku, and FH-Pori, were genotyped and serum lipid levels were measured in a large collection of Finnish population cohorts (n = 28,465), including the National FINRISK Study and the Health 2000 Study. Follow-up data were obtained from national healthcare registries. The combined prevalence of three of the five FH founder mutations (FH-North Karelia, FH-Helsinki, and FH-Pogosta) was 0.12% (95% CI 0.07-0.16%), while FH-Turku and FH-Pori were not identified in the present sample cohort. Our data suggest that the estimated total prevalence of FH in Finland is at least 0.17%. Approximately half of the 35 FH mutation carriers used lipid-lowering medication at the time of the baseline investigation. LDL cholesterol levels were on average 2 mmol/L higher in mutation carriers than in non-carriers (p < 0.001) but did not differ between FH mutation carriers with and without lipid-lowering medication. During the follow-up for 13 years, one mutation carrier encountered a probable sudden cardiac death, two mutation carriers suffered from a stroke, and one from a myocardial infarction. In Finland, at least 1 in 600 individuals is estimated to have FH. A marked undertreatment of FH was observed in LDLR mutation carriers.


Influence of the hydrophobic and hydrophilic characteristics of sliding and slider surfaces on friction coefficient: in vivo human skin friction comparison.
The objective of this study was to investigate whether hydrophilic/hydrophobic balance (Hi/Ho) of the skin surface strongly modifies the friction coefficient (mu). The Hi/Ho balance is determined using the relationship between the critical surface tension gammac (Zisman's principle:which delimits the wetting capacity) and the surface tension of water gammaH2O (water: reference element of Hi/Ho balance). Critical surface tension gammac was determined (according to Zisman's principle) through the measurement of advancing contact angle theta of a series of ethanol/water dilutions. Friction coefficient depends on several parameters: types of probe motions (rotational vs. linear), surface roughness and physicochemical parameters of surfaces in contact). In this study, the wettability parameters for six surfaces (human skin forearm, Teflon, silicone impression material 'Silflo', vinyl polysiloxane impression material 'resin' steel and glass) were measured and their influences were compared to friction coefficient mu. This study shows that the higher hydrophobia tendency of the surfaces, the lower friction coefficient. The use of three sliding materials (Teflon, steel and glass) of different Hi/Ho balance confirms the importance of these physicochemical parameters in mu. For example, Teflon with high hydrophobia has a low mu. Friction coefficient increased when hydrophobia of sliding and slider surfaces decreased. Friction coefficient value depends on the type of slider surface and its physicochemical properties. In vivo,the friction coefficient may quantify the influence of lubrificant/emolients/moisturizers. For example, the friction coefficient of hydrated skin (through the action of moisturizing products) is higher than the friction coefficient of dry skin. The relationship between the friction coefficient and the Hi/Ho balance can be reversed in the presence of water and sebum on forehead, for example.


Comparative evaluation of market spacer and home made spacer in the management of bronchial asthma.
A study was conducted to compare the efficacy of market available spacer (with valve) and home made spacer (without valve)--Bislery bottle. Fifteen patients of bronchial asthma were included in the study. With the use of both devices there was significant bronchodilator effect. The reversibility using Bislery bottle was same as with spacer (market available) while comparing the FVC, FEV1, FEV1/FVC %, FEF 25-75 and PEFR value. The difference in percent change in reversibility values by both the devices was not statistically significant (p < 0.05). We concluded that the Bislery bottle (without valve) is very cheap compared to market-available spacer and is equally effective which, therefore, can be substituted in bronchial asthma patients, who are unable to afford the cost of market available spacers.


Application of K-Means Clustering Algorithm to Commercial Parameters of Pleurotus spp. Cultivated on Representative Agricultural Wastes from Province of Guayas.
Data of the commercial parameters of Pleurotus ostreatus and Pleurotus djamor were analyzed using the data mining technique: K-means clustering algorithm. The parameters evaluated were: biological efficiency, crop yield ratio, productivity rate, nutritional composition, antioxidant and antimicrobial activities in the production of fruit bodies of 50 strains of Pleurotus ostreatus and 50 strains of Pleurotus djamor, cultivated on the most representative agricultural wastes from the province of Guayas: 80% sugarcane bagasse and 20% wheat straw (M1), and 60% wheat straw and 40% sugarcane bagasse (M2). The database of the parameters obtained in experimental procedures was grouped into three clusters, providing a visualization of the strains with a higher relation to each parameter (vector) measured.


Utilization of prenatal genetic diagnosis in women 35 years of age and older in the United States, 1977 to 1978.
As a measure of access to and acceptability of prenatal chromosomal diagnosis among older gravidas, we determined the ratio of use of prenatal diagnosis among women 35 years of age and older in Alabama, California, Manhattan, and Nebraska for the period 1977-1978. Utilization ratios were higher in 1978. Overall, utilization ratios were between 6% and 28%, well below the adjusted rates of 40% to 50% found in certain United States and British localities. Urban women tended to have higher utilization ratios than had rural women, and white women had higher ratios than had black women. Ratios were extremely low for black and rural residents. The oldest women (those greater than or equal to 40 years), who were at fivefold greater risk than women 35 to 36 years of age, had less than a onefold increase in utilization over the latter groups. The vast majority of older gravidas initiated prenatal care sufficiently early in their pregnancies to receive prenatal diagnosis. Current program strategies need to ensure access to prenatal diagnosis, especially for women greater than or equal to 40 years of age, women who are black, and women who live in rural areas.


ImmunoPET in oncology.
Due to increase of immunotherapy in oncology, it is essential to have a biological characterization of tumors. Knowing which antigens are expressed both on the surface of the tumor cell and at tumor microenvironment in order to predict the tretment response different therapeutic antibodies, has become a need. ImmunoPET is a non-invasive diagnostic imaging tool that combines the high specificity of antibodies against antigens with the high sensitivity, resolution and quantification capacity of PET imaging. With ImmunoPET we obtain a virtual biopsy of tumors, it has a big present and future in preclinical-clinical research, being already a reality in predicting and monitoring the response to treatments with monoclonal antibodies, allowing a selection of patients and therapies reaching a personalized medicine contributing to improve clinical decisions.


Associations of serum vitamin A and carotenoid levels with markers of prostate cancer detection among US men.
Associations of serum vitamin A and carotenoid levels with markers of prostate cancer detection were evaluated among 3,927 US men, 40-85 years of age, who participated in the 2001-2006 National Health and Nutrition Examination Surveys. Five recommended definitions of prostate cancer detection were adopted using total and free prostate-specific antigen (tPSA and fPSA) laboratory measurements. Men were identified as high risk based on alternative cutoffs, namely tPSA > 10 ng/ml, tPSA > 4 ng/ml, tPSA > 2.5 ng/ml, %fPSA < 25%, and %fPSA < 15%. %fPSA was defined as (fPSA÷tPSA)× 100%. Serum levels of vitamin A (retinol and retinyl esters) and carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein + zeaxanthin, lycopene) were defined as quartiles and examined as risk/protective factors for PSA biomarkers. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using binary logistic models. After adjustment for known demographic, socioeconomic, and lifestyle confounders, high serum levels of retinyl esters (tPSA > 10 ng/ml: Q4 vs. Q1 → OR = 0.38, 95% CI: 0.14-1.00) and α-carotene (%fPSA < 15%: Q4 vs. Q1 → OR = 0.49, 95% CI: 0.32-0.76) were associated with a lower odds, whereas high serum level of lycopene (tPSA > 2.5 ng/ml: Q4 vs. Q1 → OR = 1.49, 95% CI: 1.01-2.14) was associated with a greater odds of prostate cancer detection. Apart from the three significant associations observed, no other exposure-outcome association was significant. Monitoring specific antioxidant levels may be helpful in the early detection of prostate cancer.


Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis.
This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1β level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug.


Plastron-trapdoor technique for direct-vision sternal re-entry.
Repeat median sternotomy does not allow good access for retrosternal re-entry. Conversely, by using the plastron-trapdoor technique, which we describe in this report, the retrosternal tissues are dissected from the body of the sternum under direct vision, thus allowing relatively safe and wide exposure for retrosternal re-entry.


Comparison of the Subjective Elbow Value with the DASH, MEPS und Morrey Score after Olecranon Fractures.
Olecranon fractures are common injuries that can occur in patients of any age. To assess the postoperative outcome, multiple scoring systems like the DASH, MEPS und Morrey Score have been described. The goal of this paper is to compare the subjective elbow value (SEV) to these commonly used scoring systems. We hypothesized that the SEV would have a high correlation and practicability for the evaluation of elbow function after isolated olecranon injury. Clinical data of 40 patients were collected and retrospectively analysed. All patients suffered an isolated olecranon fracture and were surgically treated by tension band wiring or plate fixation. In the follow-up examinations the Mayo Score, DASH Score, Morrey Score and SEV were measured for correlation purposes. The mean follow-up time was 70.5 ± 45.6 months. The median DASH Score was 9.9 (4.1 - 20.4) and 100 (85 - 100) for the MEPS. The median Morrey Score was 98 (92 - 100). The median SEV was 90% (80 - 95%). The Pearson correlation between the DASH and SEV was -0.85 and 0.80 between the MEPS and the SEV. The SEV shows a high correlation to the most commonly used scoring systems for outcome evaluation after elbow injury. It is easy to use and can be seen as a valuable tool to assess patients after olecranon fractures.


Towards robust glucose chemical exchange saturation transfer imaging in humans at 3 T: Arterial input function measurements and the effects of infusion time.
Dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) has shown potential for tumor imaging using D-glucose as a biodegradable contrast agent. The DGE signal change is small at 3 T (around 1%) and accurate detection is hampered by motion. The intravenous D-glucose injection is associated with transient side effects that can indirectly generate subject movements. In this study, the aim was to study DGE arterial input functions (AIFs) in healthy volunteers at 3 T for different scanning protocols, as a step towards making the glucose chemical exchange saturation transfer (glucoCEST) protocol more robust. Two different infusion durations (1.5 and 4.0 min) and saturation frequency offsets (1.2 and 2.0 ppm) were used. The effect of subject motion on the DGE signal was studied by using motion estimates retrieved from standard retrospective motion correction to create pseudo-DGE maps, where the apparent DGE signal changes were entirely caused by motion. Furthermore, the DGE AIFs were compared with venous blood glucose levels. A significant difference (p = 0.03) between arterial baseline and postinfusion DGE signal was found after D-glucose infusion. The results indicate that the measured DGE AIF signal change depends on both motion and blood glucose concentration change, emphasizing the need for sufficient motion correction in glucoCEST imaging. Finally, we conclude that a longer infusion duration (e.g. 3-4 min) should preferably be used in glucoCEST experiments, because it can minimize the glucose infusion side effects without negatively affecting the DGE signal change.


Genetic variants and risk of endocrine autoimmunity in relatives of patients with Addison's disease.
Since individuals with Addison's disease (AD) present considerable co-occurrence of additional autoimmune conditions, clustering of autoimmunity was also predicted among their relatives. The study was aimed to assess circulating autoantibodies in first-degree relatives of patients with AD and to correlate them with the established genetic risk factors (PTPN22 rs2476601, CTLA4 rs231775, and BACH2 rs3757247). Antibodies were evaluated using validated commercial assays, and genotyping was performed using TaqMan chemistry. The studied cohort comprised 112 female and 75 male relatives. Circulating autoantibodies were found in 69 relatives (36.9%). Thyroid autoantibodies, that is antibodies to thyroid peroxidase (aTPO) and thyroglobulin (aTg), were detectable in 25.1 and 17.1% relatives, respectively. Antibodies to 21-hydroxylase (a21OH) were found in 5.8% individuals, and beta cell-specific antibodies to ZnT8, GAD, and IA2 were found in 7.5, 8.0, and 2.7%, respectively. The prevalence of a21OH (P = 0.0075; odds ratio (OR) 7.68; 95% CI 1.903-36.0), aTPO (P < 0.0001; OR 3.85; 95% CI 1.873-7.495), and aTg (P < 0.0001; OR 7.73; 95% CI 3.112-19.65), as well as aGAD (P = 0.0303; OR 3.38; 95% CI 1.180-9.123) and aZnT8 (P = 0.032; OR 6.40; 95% CI 1.846-21.91), was significantly increased in carriers of rs2476601 T allele. Moreover, T allele appeared to be a risk factor for multiple circulating autoantibody specificities (P = 0.0009; OR 5.79; 95% CI 1.962-15.81). None of the studied autoantibodies demonstrated significant association with rs231775 in CTLA4 (P > 0.05), and only weak association was detected between BACH2 rs3757247 and circulating aTPO (P = 0.0336; OR 2.12; 95%CI 1.019-4.228). In conclusion, first-degree relatives of patients with AD, carriers of the PTPN22 rs2476601 T allele, are at particular risk of developing autoantibodies to endocrine antigens.


Effective anticoagulation by argatroban during immunoadsorption therapy for malignant rheumatoid arthritis with a high polymorphonuclear leukocyte elastase level.
Polymorphonuclear leukocyte elastase (PMNE) is a glycoprotein with a molecular weight of about 30000 and exists in 3 isozymes (1). It has a biological role in host defense mechanisms, but it sometimes induces abnormal blood coagulation and injury of the vascular intima (1,2). We were not able to obtain a satisfactory anticoagulant effect when using heparin during immunoadsorption therapy in a patient with malignant rheumatoid arthritis and high PMNE level, but found that argatroban, a selective antithrombin agent, produced satisfactory anticoagulation. This finding is interesting as far as the various pathologic roles of PMNE are attracting increasing clinical attention (1,2,3).


A protective role of nintedanib in peritoneal fibrosis through H19-EZH2-KLF2 axis via impeding mesothelial-to-mesenchymal transition.
Peritoneal fibrosis (PF), a common complication of long-term peritoneal dialysis, accounts for peritoneal ultrafiltration failure to develop into increased mortality. Nintedanib has previously been shown to protect against multi-organ fibrosis, including PF. Unfortunately, the precise molecular mechanism underlying nintedanib in the pathogenesis of PF remains elusive. The mouse model of PF was generated by chlorhexidine gluconate (CG) injection with or without nintedanib administration, either with the simulation for the cell model of PF by constructing high-glucose (HG)-treated human peritoneal mesothelial cells (HPMCs). HE and Masson staining were applied to assess the histopathological changes of peritoneum and collagen deposition. FISH, RT-qPCR, western blot and immunofluorescence were employed to examine distribution or expression of targeted genes. Cell viability was detected using CCK-8 assay. Cell morphology was observed under a microscope. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were applied to validate the H19-EZH2-KLF2 regulatory axis. Aberrantly overexpressed H19 was observed in both the mouse and cell model of PF, of which knockdown significantly blocked HG-induced mesothelial-to-mesenchymal transition (MMT) of HPMCs. Moreover, loss of H19 further strengthened nintedanib-mediated suppressive effects against MMT process in a mouse model of PF. Mechanistically, H19 could epigenetically repressed KLF2 via recruiting EZH2. Furthermore, TGF-β/Smad pathway was inactivated by nintedanib through mediating H19/KLF2 axis. In summary, nintedanib disrupts MMT process through regulating H19/EZH2/KLF2 axis and TGF-β/Smad pathway, which laid the experimental foundation for nintedanib in the treatment of PF.


Synthesis and comparative molecular field analysis (CoMFA) of argentatin B derivatives as growth inhibitors of human cancer cell lines.
Synthesis, characterization, anticancer activity, and comparative molecular field analysis (CoMFA) of 14 argentatin B (1) analogs are described. The effect of argentatin B derivatives on the growth of K562 (leukemia), PC-3 (prostate), U251 (CNS), and HCT-15 (colon) human cancer cell lines was determined using the sulforhodamine B test. The most active compound in this series, 2-formyl-(16beta,24R)-16,24-epoxy-25-hydroxycycloart-1-en-3-one (12), was about 35-50 times more potent than argentatin B (1). Structures were built using the X-ray crystallography of six derivatives for 3D modeling with Sybyl6.9. CoMFA of Log (1/IC50) in K562 cell line gave q2 = 0.507, r2 = 0.907, and three components. The standard deviation CoMFA contours indicate that increased activity is associated with a bulky group at C-2, a C1-C2 double bond, and low electronic density at C-25. Experimental Log P values for argentatin B and one derivative were 1-2 Log units more hydrophilic than the calculated CLog P values.


Mechanistic roles of tyrosine phosphorylation in reversible amyloids, autoinhibition, and endosomal membrane association of ALIX.
Human apoptosis-linked gene-2 interacting protein X (ALIX), a versatile adapter protein, regulates essential cellular processes by shuttling between late endosomal membranes and the cytosol, determined by its interactions with Src kinase. Here, we investigate the molecular basis of these transitions and the effects of tyrosine phosphorylation on the interplay between structure, assembly, and intramolecular and intermolecular interactions of ALIX. As evidenced by transmission electron microscopy, fluorescence and circular dichroism spectroscopy, the proline-rich domain of ALIX, which encodes binding epitopes of multiple cellular partners, formed rope-like β-sheet-rich reversible amyloid fibrils that dissolved upon Src-mediated phosphorylation and were restored on protein-tyrosine phosphatase 1B-mediated dephosphorylation of its conserved tyrosine residues. Analyses of the Bro1 domain of ALIX by solution NMR spectroscopy elucidated the conformational changes originating from its phosphorylation by Src and established that Bro1 binds to hyperphosphorylated proline-rich domain and to analogs of late endosomal membranes via its highly basic surface. These results uncover the autoinhibition mechanism that relocates ALIX to the cytosol and the diverse roles played by tyrosine phosphorylation in cellular and membrane functions of ALIX.


Adsorption of sulfamethoxazole via biochar: The key role of characteristic components derived from different growth stage of microalgae.
Converting microalgal biomass residues into biochar (BC) after microalgal wastewater treatment is a popular approach that can produce an adsorbent to treat refractory organic pollutants. Moreover, the adsorption efficiency via BC is closely associated with the surface morphology, which may be determined by the composition of the microalgal biomass. However, the intrinsic relationship and advanced mechanism between the adsorption efficiency and microalgal composition have not been thoroughly investigated. In this work, four microalgal BCs were prepared from Chlamydomonas sp. QWY37 (CBC) after collection from four different growth stages of microalgal biomass during wastewater treatment. The adsorption performance for sulfamethoxazole indicates that the CBC collected in the mid-log phase (CBCL-M) possessed the best adsorption capacity (287.89 mg/g) owing to the higher decomposition of the microalgal cellular protein concentration (70%). Meanwhile, a higher protein content contributed to the largest specific surface area (42.16 m2/g), maximum pore volume (0.037 cm3/g) and abundant surface functional groups of the CBCL-M. Furthermore, based on the theoretical calculation of the structural analysis, the adsorption mechanism was a multilayer adsorption process in accordance with the Freundlich isotherm. Additionally, the strong hydrogen bond, electron donor-acceptor interaction and electrostatic attraction were the main adsorption mechanisms due to the carboxyl/ester functional groups. The results of this research provide a novel perspective on the reasonable harvest of microalgal biomass for BC fabrication and large-scale implementation of microalgal BC in future applications.


The isolation from a unicellular organism, Dictyostelium discoideum, of a highly-related cdc2 gene with characteristics of the PCTAIRE subfamily.
It has been suggested that cell-type determination in Dictyostelium discoideum is dependent on the position of a cell in the cell cycle at the time of starvation. In order to understand the molecular basis of this phenomenon, we initiated studies on the cell cycle and have recently described the isolation of a Dictyostelium gene encoding a homolog of the Cdc2 kinase. We have been unable to isolate additional cdc2 genes from Dictyostelium using polymerase chain reaction technology, but have isolated a gene that is highly related to cdc2. The encoded product is a protein of 33 kDa that shares over 60% identity to the cell-cycle-dependent Cdc2 kinases. However, despite this high level of identity, the gene is not capable of complementing the temperature-sensitive cdc28 mutant of Saccharomyces cerevisiae. Furthermore, the gene product shares some characteristics with the recently described PCTAIRE proteins; it contains a PCTAIRE motif instead of the Cdc2 kinase conserved PSTAIRE sequence, it does not possess the conserved GDSEID sequence that is involved in the activation of the enzyme and it has a Ser in the position equivalent to Thr-161. However, the Dictyostelium protein exhibits a slightly higher level of identity to the Cdc2 kinases than to the PCTAIRE proteins and is smaller than any of the PCTAIRE proteins thus far identified. Since the gene product has characteristics of both Cdc2 kinases and PCTAIRE proteins we have designated the gene product Crp (Cdc2-Related PCTAIRE) kinase. The gene is expressed as two transcripts of 1.5 and 1.8 kb and the expression is developmentally regulated with low levels of mRNA in vegetative cells and significantly higher levels throughout the remainder of the differentiation process. These results suggest the possibility that the gene product is involved in Dictyostelium differentiation rather than growth. This report is the first evidence for a highly-related cdc2 gene in unicellular eukaryote. It also demonstrates for the first time that a unicellular eukaryote expresses a protein containing the PCTAIRE sequence.


A comparative study of different glycosylation methods for the synthesis of D-mannopyranosides of Nalpha-fluorenylmethoxycarbonyl-trans-4-hydroxy-L-proline allyl ester.
The synthesis of Nalpha-fluorenylmethoxycarbonyl-trans-4-hydroxy-4-O-[(2,3,4,6-tetra-O-acetyl)-alpha-d-mannopyranosyl]-l-proline allyl ester and Nalpha-fluorenylmethoxycarbonyl-trans-4-hydroxy-4-O-[(2,3,4,6-tetra-O-benzoyl)-alpha-d-mannopyranosyl]-l-proline allyl ester is described. Glycosylation using Königs-Knorr conditions with a benzoyl protected glycosyl donor provided the optimum method. Removal of the allyl ester gave two mannosylated building blocks suitable for solid phase glycopeptide synthesis.


Microglial heterogeneity in aging and Alzheimer's disease: Is sex relevant?
Neurodegenerative diseases and their associated cognitive decline are known to be more prevalent during aging. Recent evidence has uncovered the role of microglia, the immunocompetent cells of the brain, in dysfunctions linked to neurodegenerative diseases such as is Alzheimer's disease (AD). Similar to other pathologies, AD is shown to be sex-biased, with females being more at risk compared to males. While the mechanisms driving this prevalence are still unclear, emerging data suggest the sex differences present in microglia throughout life might lead to different responses of these cells in both health and disease. Furthermore, microglial cells have recently been recognized as a deeply heterogeneous population, with multiple subsets and/or phenotypes stemming from diverse parameters such as age, sex or state of health. Therefore, this review discusses microglial heterogeneity during aging in both basal conditions and AD with a focus on existing sex differences in this process.


Coping with suicide' burning scar's disfigurement among Kurdish women in Iraq (Kurdistan).
Suicide is one of the most important causes of death in the world. A critical problem that Iraqi women in Kurdistan are facing is self-immolation. Deformity caused by burn can have many psychological effects on the individuals, including self-image disorder, loss of quality of life, low self-confidence, and disturbances in social interactions. A qualitative research method with a grounded theory approach was used to achieve the research objectives. Sampling started purposefully and continued with theoretical sampling until access to sufficient knowledge about the phenomenon under investigation. In this study, 22 in-depth interviews were carried out with 19 women participants who had committed self-immolation. After the data analysis, six main categories were formed, including; 1- Facing the inevitable harsh reality. 2- Experiencing negative reactions from others 3- Drowning in the vicious cycle of hopelessness and regret. 4- A bitter journey into the whirlpool of fear and uncertainty. 5- Germination of the hope buds. 6- Re-building weakened self-esteem. "Stepping on the rugged path of distorted image reconstruction" was the core variable in the study. Although people take some steps to adapt to the situation and deformity, they do not achieve full acceptance of the present circumstances. In this process, the person hopes to regain the lost beauty and does not effortlessly accept the deformity. Instead, she will try everything to get rid of deformity and restore the lost beauty. During the adaptation process, nurses and health care providers, the family and the community have a unique role in accelerating or slowing the process of adaptation.


Early sequential lesions during development of experimental gastric cancer with special reference to dysplasias.
The early sequential development of gastric cancer was studied with experimental animals and examined with respect to what conclusions can be drawn for understanding carcinogenesis in man. After limited oral administration of N-methyl-N'nitro-N-nitrosoguanidine to 174 rats carcinomas developed in most cases directly from the otherwise unchanged mucosa through various successive stages of transformation, without passing through a benign-appearing proliferative or neoplastic epithelial lesion. Focal dysplasia grade I was the first recognizable change observed by light microscopy, followed by dysplasia grade II, and subsequently dysplasia grade III. In spite of very similar morphological characteristics, the experimentally induced dysplasias cannot be simply equated in their etiology and biological behavior with the dysplasias of the human stomach. Dysplasias of grade I and II commonly found in man are usually associated with a chronic gastritis; they are located in the upper third of the mucosa and are for the most part reversible. The experimental dysplasias occuring in the proliferative zone of an otherwise undisturbed mucosa must be considered potentially premalignant, as they are irreversible and develop progressively. This finding points out that in man dysplasias grade III within the regenerative zone of non-inflammatory mucosa should be considered particularly as possible precursors of gastric carcinomas.


Physical methods for enhancing drug absorption from the gastrointestinal tract.
Overcoming the gastrointestinal (GI) barriers is a formidable challenge in the oral delivery of active macromolecules such as peptide- and protein- based drugs. In the past four decades, a plethora of formulation strategies ranging from permeation enhancers, nanosized carriers, and chemical modifications of the drug's structure has been investigated to increase the oral absorption of these macromolecular compounds. However, only limited successes have been achieved so far, with the bioavailability of marketed oral peptide drugs remaining generally very low. Recently, a few approaches that are based on physical interactions, such as magnetic, acoustic, and mechanical forces, have been explored in order to control and improve the drug permeability across the GI mucosa. Although in the early stages, some of these methods have shown great potential both in terms of improved bioavailability and spatiotemporal delivery of drugs. Here, we offer a concise, yet critical overview of these rather unconventional technologies with a particular focus on their potential and possible challenges for further clinical translation.


Clinical characteristics and postoperative complications as predictors of radiation toxicity after treatment with I125 Eye Plaque Brachytherapy for Uveal Melanomas.
I125 Eye Plaque brachytherapy is the standard treatment for medium-sized uveal melanomas (UM). Patients develop radiation toxicities (RTT), including radiation maculopathy (RM), radiation neovascular glaucoma/iris neovascularization (RNGI) and radiation optic neuropathy (RON). We aim to investigate demographics, pretreatment tumor characteristics and posttreatment complications as predictors of RTT. An IRB-approved single-institution retrospective chart review was performed from 2011 to 2019 for patients with posterior UM treated with brachytherapy. We collected demographics, pretreatment tumor characteristics and posttreatment complications. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using logistic regression model. Hazard ratios (HR) and corresponding p-values were reported. All tests were two-sided; statistical significance was considered when p<0.05. Two hundred and fifty eight patients were evaluated. Median follow-up was 33.50 months (range 3.02-97.31). 178 patients (69.0%) had RTT. 131 patients (50.8%) developed RM. Fifty-six patients (21.7%) developed RON. Nineteen patients (7.4%) developed RNGI. UVA found shorter distance to fovea (DF) (p = 0.04), posttreatment exudative retinal detachment (PERD) (p = 0.001) and posttreatment vitreous hemorrhage (PVH) (p = 0.001) are associated with RTT. MVA found shorter DF (HR=1.03, p = 0.04), PERD (HR=2.52, p = 0.01) and PVH (HR=3.34, p = 0.006) are associated with RTT. MVA found female sex (HR=1.731, p = 0.031) and tumor height (HR=1.13, p = 0.013) are associated with RM and pretreatment retinal detachment (HR=3.41, p<0.001) is associated with RON. Shorter DF, PERD and PVH are associated with RTT; female sex and tumor height are associated with RM and tumor height is associated with RON. These findings serve as prognostic tools to counsel patients and promote early intervention in management of RTT.


In vitro myometrial contractility reflects indication for caesarean section.
To assess the extent to which in vitro measurements of myometrial contractility reflect the clinical indication for caesarean section. A prospective, observational hypothesis-generating study. Women were recruited from Liverpool Women's NHS Foundation Trust and experiments were performed in the Physiology Department at the University of Liverpool. Myometrial samples were taken from women undergoing a caesarean section during labour (n = 50) or from women having a repeat nonlabouring caesarean section (n = 70). The demographic characteristics of the women and indications for current and previous caesarean sections were recorded. The force, frequency and duration of spontaneous contractions of myometrial strips, and changes in the intracellular calcium concentration of the strips, were measured. Kruskall-Wallis and post hoc tests were used to assess the significance of differences between groups. Samples from women whose caesarean section was for fetal distress/acidosis (scalp pH <7.2) contracted with more force than those from women whose caesarean section was for delay in the first stage of labour (P < 0.001). For repeat, nonlabouring caesarean sections, samples from women whose first caesarean section was for fetal distress/acidosis also contracted with more force than did samples from women whose first caesarean section was for delay in the first stage of labour (P = 0.03). These findings suggest that the myometrium contracts with greater force in women who have a caesarean section for fetal distress.


Life table analysis of intrauterine insemination pregnancy rates for couples with cervical factor, male factor, and idiopathic infertility.
A retrospective analysis of 231 couples undergoing 762 IUI cycles revealed that 63 of 64 pregnancies occurred within four IUI cycles. It is recommended that couples undergoing IUI treatment who fail to conceive within four cycles consider a modification of treatment strategy.


Comparative analysis of hippocampal transcriptional features between major depressive disorder patients and animal models.
Major depressive disorder (MDD) is a psychiatric disorder caused by various etiologies. Chronic stress models are used to simulate the heterogeneous pathogenic processes of depression. However, few studies have compared transcriptional features between stress models and MDD patients. We generated hippocampal transcriptional profiles of the chronic social defeat model by RNA sequencing and downloaded raw data of the same brain region from public databases of the chronic unpredictable mild stress model, the learned helplessness model, and MDD patients. Differential expression and gene co-expression analyses were integrated to compare transcriptional features between stress models and MDD patients. Each stress model shared 11.4% to 16.3% of differentially expressed genes with MDD patients. Functional analysis at the gene expression level identified altered ensheathment of neurons in both stress models and MDD patients. At the gene network level, each stress model shared 20.9% to 41.6% of co-expressed genes with MDD patients. Functional analysis based on these genes found that axon guidance signaling is the most significantly enriched pathway that was shared by all stress models and MDD patients. This study was limited by considering only a single brain region and a single sex of stress model animals. Our results show that hippocampal transcriptional features of stress models partially overlap with those of MDD patients. The canonical pathways of MDD patients, including ensheathment of neurons, PTEN signaling, and axonal guidance signaling, were shared with all stress models. Our findings provide further clues to understand the molecular mechanisms of depression.


SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans.
We tested the hypothesis that reductions in the cellular deacetylase, sirtuin-1 (SIRT-1), contribute to vascular endothelial dysfunction with ageing via modulation of endothelial nitric oxide synthase (eNOS) acetylation/activation-associated nitric oxide (NO) production. In older (30 months, n = 14) vs. young (5-7 months, n = 16) B6D2F1 mice, aortic protein expression of SIRT-1 and eNOS phosphorylated at serine 1177 were lower (both P < 0.05), and acetylated eNOS was 6-fold higher (P < 0.05), whereas total eNOS did not differ (P = 0.65). Acetylcholine (ACh)-induced peak endothelium-dependent dilatation (EDD) was lower in isolated femoral arteries with ageing (P < 0.001). Incubation with sirtinol, a SIRT-1 inhibitor, reduced EDD in both young and older mice, abolishing age-related differences, whereas co-administration with l-NAME, an eNOS inhibitor, further reduced EDD similarly in both groups. Endothelium-independent dilatation to sodium nitroprusside (EID), was not altered by age or sirtinol treatment. In older (64 ± 1 years, n = 22) vs. young (25 ± 1 years, n = 16) healthy humans, ACh-induced forearm EDD was impaired (P = 0.01) and SIRT-1 protein expression was 37% lower in endothelial cells obtained from the brachial artery (P < 0.05), whereas EID did not differ. In the overall group, EDD was positively related to endothelial cell SIRT-1 protein expression (r = 0.44, P < 0.01). Reductions in SIRT-1 may play an important role in vascular endothelial dysfunction with ageing. SIRT-1 may be a key therapeutic target to treat arterial ageing.


Nontraumatic rupture of lumbar artery causing an intravertebral body pseudoaneurysm: treatment by transcatheter embolization.
We report a case of nontraumatic rupture of the lumbar artery that led to a pseudoaneurysm in the vertebral body and massive retroperitoneal to retropleural hematoma. The pseudoaneurysm was successfully treated by endovascular embolization. To our knowledge, idiopathic rupture of the lumbar artery has been reported in a limited number of cases and pseudoaneurysm formation in the vertebral body has not been presented in the literature. The etiology of hemorrhage has been discussed based on CT, MRI, and three-dimensional rotational angiography.


Accelerated-strategy renal replacement therapy for critically ill patients: A systematic review and meta-analysis.
The aim of this study was to investigate the clinical effect and safety of accelerated-strategy initiation of renal replacement therapy (RRT) in critically ill patients. PubMed, Embase, OVID, EBSCO, and the Cochrane Library databases were searched for relevant articles from inception to December 30, 2020. Only RCTs that compared the clinical efficacy and safety between accelerated-strategy RRT and standard-strategy RRT among critically ill adult patients with acute kidney injury (AKI) were included. The primary outcome was 28-day mortality. A total of 5279 patients in 12 RCTs were included in this meta-analysis. The 28-day mortality rates of patients treated with accelerated and standard RRT were 37.3% (969/2596) and 37.9% (976/2573), respectively. No significant difference was observed between the groups (OR, 0.92; 95% CI, 0.70-1.12; I2 = 60%). The recovery rates of renal function were 54.5% and 52.5% in the accelerated- and standard-RRT groups, respectively, with no significant difference (OR, 1.03; 95% CI, 0.89-1.19; I2 = 56%). The rate of RRT dependency was similar in the accelerated- and standard-RRT strategies (6.7% vs 5.0%; OR, 1.11; 95% CI, 0.71-1.72; I2 = 20%). The accelerated-RRT group displayed higher risks of hypotension, catheter-related infection, and hypophosphatemia than the standard-RRT group (hypotension: OR, 1.26; 95% CI, 1.10-1.45; I2 = 36%; catheter-related infection: OR, 1.90; 95% CI, 1.17-3.09; I2 = 0%; hypophosphatemia: OR, 2.11; 95% CI, 1.43-3.15; I2 = 67%). Accelerated RRT does not reduce the risk of death and does not improve the recovery of kidney function among critically ill patients with AKI. In contrast, an increased risk of adverse events was observed in patients receiving accelerated RRT. However, these findings were based on low quality of evidence. Further large-scale RCTs is warranted.


Global coronavirus disease 2019: What has daily cumulative index taught us?
In addition to the absolute case number, a rapid increase in the number of COVID-19 cases within a short time results in insufficiency of healthcare systems and further negatively affects patient outcomes. This study was conducted to investigate the association between the outcomes of COVID-19 patients and daily cumulative index (DCI), which was defined as the average daily number of new cases of COVID-19 and calculated by cumulative cases/number of days between the first reported case and March 6, 2020, by country. Spearman's rank correlation analyses were conducted to evaluate the relationship between mortality, incidence, and DCI. In this study, DCI was positively correlated with incidence (adjusted risk ratio [aRR] = 1.01, 95% confidence interval [CI] = 1.00-1.02, P < 0.01). Higher correlation was observed between mortality and DCI (mortality rate: r = 0.397, P = 0.018; mortality per 1 000 000 people: r = 0.0.428, P = 0.004) than between disease incidence and DCI. DCI remained statistically significantly associated with mortality per 1 000 000 people after adjustment of Health Care Index (aRR = 1.02, 95% CI = 1.01-1.03, P < 0.001) or Healthcare Access and Quality Index (aRR = 1.02, 95% CI = 1.01-1.04, P < 0.01. Reducing DCI through strict infection control measures can help slow the number of new COVID-19 cases and further improve outcomes in COVID-19 patients.


Characterization of H5N1 highly pathogenic mink influenza viruses in eastern China.
Members of the H5 subtype of highly pathogenic avian influenza viruses pose a great threat to both poultry and humans with severe consequences for both industry and public health sectors. Here, we isolated and characterized two H5N1 highly pathogenic influenza viruses in deceased mink from eastern China. Phylogenetic analyses showed that the G15 and XB15 viruses belonged to clade 126.96.36.199b and 184.108.40.206e, respectively. Both of these viruses were highly pathogenic in chickens. They were also shown to exhibit moderate to high pathogenicity in mice without pre-adaptation. Further, the mink influenza viruses had severe antigenic drift with corresponding Re-6 vaccine and current vaccines may fail to confer protection against these H5N1 viruses in poultry.


Analysis of taste bud innervation based on glycoconjugate and peptide neuronal markers.
Primary gustatory neurons and their peripheral and central processes were evaluated histochemically in the geniculate and petrosal cranial nerve ganglia, lingual fungiform taste buds, and the nucleus of the solitary tract (NST) using 1) the plant lectin Griffonia simplicifolia I-B4, which binds specifically to D-galactose residues and selectively labels primarily nonpeptide-containing peripheral somatosensory neurons, and 2) calcitonin gene-related peptide immunoreactivity (CGRP-IR), which labels most peptidergic somatosensory neurons. Lectin reactivity was expressed by the vast majority of geniculate and petrosal ganglion cells, while CGRP-IR labeled very few cells. Peripherally, gustatory intragemmal axons penetrating fungiform taste buds were labeled only by the lectin and were depleted following chorda tympani transection. However, both lectin-labeled and CGRP-IR subpopulations of somatosensory perigemmal axons surrounding the taste buds were observed and were eliminated by section of the lingual nerve. The differing brainstem projection patterns of lectin-reactive vs. CGRP-IR central axons reflected their distinct ganglionic origins and the differential distributions of lectin reactivity and CGRP-IR among taste buds. Central lectin-reactive terminals were found throughout the entire rostrocaudal extent of the NST, including its rostral lateral "gustatory" zone; the extensive lectin-reactive visceral afferent projection can be presumed to have originated mainly from the large proportion of lectin-labeled neurons in the nodose ganglion. The lectin also prominently and selectively labeled the area postrema. CGRP-IR central terminals, however, was relatively sparse and restricted primarily to the caudal and medial "visceral" divisions of the NST. The results are discussed with respect to the possible functional implications of cell surface glycoconjugate expression by gustatory axons innervating taste bud receptor cells of the tongue.


The five problems of irreversibility.
Thermodynamics has a clear arrow of time, characterized by the irreversible approach to equilibrium. This stands in contrast to the laws of microscopic theories, which are invariant under time-reversal. Foundational discussions of this "problem of irreversibility" often focus on historical considerations, and do therefore not take results of modern physical research on this topic into account. In this article, I will close this gap by studying the implications of dynamical density functional theory (DDFT), a central method of modern nonequilibrium statistical mechanics not previously considered in philosophy of physics, for this debate. For this purpose, the philosophical discussion of irreversibility is structured into five problems, concerned with the source of irreversibility in thermodynamics, the definition of equilibrium and entropy, the justification of coarse-graining, the approach to equilibrium and the arrow of time. For each of these problems, it is shown that DDFT provides novel insights that are of importance for both physicists and philosophers of physics.


Comparison of 2 monocular pupillometers and an autorefractor for measurement of the dark-adapted pupil diameter.
To compare the performance of the Marco Nidek ARK-530A autorefractor pupillometer function and the Keeler PupilScan II pupillometer (study pupillometer) against the clinical standard NeurOptics PLR-200 pupillometer (standard pupillometer) for measurement of the dark-adapted pupil diameter. Department of Ophthalmology and Visual Sciences, Texas Tech University Health Sciences Center, Lubbock, Texas, USA. Evaluation of diagnostic test or technology. Subjects aged 20 to 60 years were dark-adapted for 2 minutes at 1 lux ambient illumination. Accommodation was controlled through distance fixation. The dark-adapted pupil diameter was measured with the standard pupillometer, then the study pupillometer, then the autorefractor. Results were compared using Bland-Altman graphs. The autorefractor underestimated the dark-adapted pupil diameter by a mean of 1.03 mm (range 0.0 to 2.3 mm). Thirty-four (85%) measurements were at least 0.5 mm smaller than the corresponding standard pupillometer values, and 16 (40%) were more than 1.0 mm smaller. Observer experience did not improve accuracy. The study pupillometer underestimated the dark-adapted pupil diameter by a mean of 0.31 mm (range 0.0 to 0.9 mm). Ten (25%) measurements were at least 0.5 mm smaller than the standard pupillometer values. Accuracy improved in the final 10 subjects (study pupillometer smaller; mean difference 0.16 mm; range 0.0 to 0.4 mm). The autorefractor pupillometry function had an unpredictable negative bias (variable underestimation of dark-adapted pupil diameter). The study pupillometer had a slight negative bias but required significant examiner skill and knowledge of normal pupil movement to obtain a valid result. Neither device was sufficiently accurate for confident surgical planning or clinical diagnosis. Neither author has a financial or proprietary interest in any material or method mentioned.


The impact of ambient air pollution on lung function and respiratory symptoms in elite athletes.
Air pollution has become a significant public health concern. During exercise, many physiological factors are thought to increase the effects of air pollution. Air pollution most affects lung function and respiratory symptoms. We investigated the association between lung function, respiratory symptoms, and air pollutant concentration with meteorological factors in elite sports athletes. A total of 59 elite sports athletes from the Korea National Sports University participated in this prospective, observational study from September 2019 to June 2020. At ten visits, lung function and respiratory symptoms were obtained after a training session. We measured six air pollutants, including SO2, CO, O3, NO2, PM10, and PM2.5, and two meteorological factors, including humidity and temperature. Air pollutants and meteorological factors were measured by two nearest depositories of the national air pollution information system in Korea. In a single-pollutant model, PM2.5, PM10, NO2, and CO were inversely associated with both FEV1 and FEV6, 10 μg/m3 in PM2.5 was associated with a 32.31 mL decrease in FEV1 and a 36.93 mL decrease in FEV6. Meanwhile, O3 and temperature had positive associations with both FEV1 (13.00 and 3.15 mL) and FEV6 (16.91 and 4.76 mL) and humidity with FEV6 (11.98 mL). In the multi-pollutant model at lag 0, FEV1 was associated negatively with O3 and NO2 (-50.68 and -6.87 mL) and positively with SO2 and temperature (65.76 and 8.08 mL). In the multi-pollutant model at lag 6, temperature was associated with FEV1 and FEV6 (6.01 and 8.89 mL). PM2.5, PM10, NO2, CO, and temperature were significantly associated with FEV1 and FEV6 through lag 0-6. Air pollutants and meteorological factors are associated with lung function and respiratory symptoms and have cumulative effects among elite athletes. In the multi-pollutant model, temperature has the most significant effect on lung function.


Transient RNA silencing of tissue factor pathway inhibitor-2 modulates lung cancer cell invasion.
Tissue Factor Pathway Inhibitor-2 (TFPI-2) is a potent inhibitor of plasmin which activates metalloproteinases (MMPs) involved in extracellular matrix (ECM) degradation. Its secretion in ECM makes TFPI-2 a potential inhibitor to regulate tumour invasion and metastasis. Moreover, TFPI-2 is frequently downregulated, particularly in aggressive cancers. In this study, we silenced TFPI-2 in the NCI-H460 non-small cell lung cancer cell line and evaluated the role of TFPI-2 in cell invasion and its impact on MMPs expression. As the effects of siRNA are transient, the consequences of both gene silencing and restoration to normal expression could be studied kinetically in the same cells. We showed that TFPI-2 expression by NCI-H460 cells was effectively downregulated using specific small interfering RNA and this silencing was associated with an increase in the invasive potential of tumour cells while migration was not affected. We also showed that mRNA levels and protein expression of MMP-2, -3, -9, -14 were not influenced by TFPI-2 silencing. Moreover, the gelatinase activity of MMP-2 and MMP-9 was unmodified. In contrast, MMP-1 mRNA levels and protein were significantly and similarly increased in cells transfected with TFPI-2 siRNA. In conclusion, this study confirms that TFPI-2 downregulation can contribute to tumour invasion of lung cancer cells.


Impaired fibrinolytic capacity and tissue plasminogen activator release in patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA).
To assess the role of the fibrinolytic system in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we determined the components of this system in a retrospective study, including 16 patients with restenosis (gr. A) and 19 patients with long-term success (gr. B). In both groups at baseline fibrinolytic activity (FA) is unchanged, whereas tissue plasminogen activator antigen (tPA-Ag) is significantly increased (gr. A: 147.0%; gr. B: 139.8%; p less than 0.01). Fibrinolytic capacity (FC) and tPA-Ag release are significantly reduced in the restenosis group (FC: 46.5%, p less than 0.05; tPA-Ag release: 48.3%, p less than 0.01) compared to normal controls as well as to gr. B (FC: 84.3%, p less than 0.05; tPA-Ag release: 79.0%, p less than 0.05). Relating to the contact activation system, F XII (79.5%, p less than 0.05) is significantly, and F XI (82.3%) is clearly reduced in gr. A. Protein C (PC) is significantly elevated in gr. B (117.5%, p less than 0.05). There is a negative correlation between plasminogen activator inhibitor (PAI 1) and HDL-cholesterol (r = 0.37, p less than 0.05). It appears, that there is a typical pattern of defective fibrinolysis in patients with restenosis after PTCA and that this might be a pathogenetic factor in the development of restenosis.


In vitro induction of cytotoxic effector cells against human neoplasms. I. Sensitization conditions and effect of cryopreservation on the induction and expression of cytotoxic responses to allogeneic leukemia cells.
Peripheral blood lymphocytes (PBL) from normal human donors were sensitized in vitro against allogeneic human acute myelocytic leukemia (AML) cells by means of an unidirectional mixed lymphocyte-tumor cell culture (MLTC) technique. The cytotoxic responsiveness of the sensitized lymphocytes, as determined in vitro by the 51Cr-release assay, varied among individual lymphocyte donors and was greatly dependent on the sensitization culture conditions. Induction of cytotoxic effector cells was augmented appreciably by adding to the cultures minute amounts of the immunopotentiating agent MER-BCG. Responding lymphocytes and stimulating leukemia cells cryopreserved for several weeks in liquid nitrogen were as effective as fresh cells in generating effector lymphocytes; the cytotoxic capacity of already sensitized lymphocytes was fully retained by cryopreservation. The implications of these findings for possible clinical employment of in vitro sensitized lymphocytes in adoptive immunotherapy of cancer are discussed.


Regulatory activity of human CD4 CD25 T cells depends on allergen concentration, type of allergen and atopy status of the donor.
Regulatory CD4+ CD25+ FoxP3-positive T cells (Treg) are functional in most atopic patients with allergic rhinitis and are able to inhibit T helper type 1 (Th1) and Th2 cytokine production of CD4+ CD25- T cells. This study was designed to analyse the following additional aspects: influence of allergen concentration, influence of the type of allergen, and influence of the atopy status of the donor on the strength of the regulatory activity. CD4+ CD25- T cells from healthy non-atopic controls or from grass-pollen-allergic or wasp-venom-allergic donors were stimulated alone or in the presence of Treg with autologous mature monocyte-derived dendritic cells which were pulsed with different concentrations of the respective allergens. Treg from grass-pollen-allergic donors failed to inhibit proliferation but not cytokine production of CD4+ CD25- T cells at high antigen doses while Treg from non-atopic donors did not fail at these allergen concentrations. Proliferative responses and cytokine production of CD4+ CD25- T cells from most of the examined wasp-venom-allergic patients were not inhibited at any concentration of wasp venom. The use of wasp venom- or phospholipase A2-pulsed dendritic cells for stimulation of CD4+ CD25- T cells from donors who were not allergic to wasp stings only resulted in an inhibited proliferation and Th2 cytokine production by Treg at 10-fold lower than the optimal concentration, while interferon-gamma production was inhibited at all concentrations investigated. These data demonstrate that in allergic diseases the function of Treg is dependent on the concentration and the type of the respective allergen with different thresholds for individual allergens and patients.


All that is hypogonadal in haemochromatosis is not due to iron deposition.
Hereditary haemochromatosis (HH) is an autosomal recessive condition resulting in excessive gastrointestinal absorption of iron, which may be deposited in various organs. Apart from diabetes, hypogonadism is the most common endocrinopathy associated with HH and is usually secondary to excess iron deposition in the anterior pituitary gland. We present three patients with HH and hypogonadism. Careful clinical and biochemical analysis revealed that the hypogonadism was due to causes other than iron deposition. This series illustrates the importance of having a high degree of clinical suspicion, even when dealing with what may clinically appear to be a straight-forward clinical problem.


Psoriatic arthritis in Africa.
Psoriatic arthritis is a chronic immune-mediated inflammatory arthritis associated with the skin condition psoriasis. Although there is a large body of evidence regarding epidemiology, outcomes, and response to therapy from the Western world, there is a dearth of published literature from the African continent. There are many challenges responsible for this. Lack of resources, both human and financial, an enormous disease burden, and a focus on communicable diseases leave an unmet need for this important disease. This review explores and identifies these challenges and proposes ways to improve and overcome these deficiencies. We discuss the epidemiology of psoriatic arthritis in Africa, postulating the role of genetic and environmental factors, looking at the role of HLA-B 23, HLA-B 17, and HLA-B 8. Dietary intake as a contributing factor to the low prevalence of psoriatic arthritis and psoriasis is also discussed. Challenges on the African continent regarding limited access to specialised units/specialists, delay in diagnosis, limited attention by healthcare authorities to non-communicable diseases, and the difficulties in implementing international recommendations on the African continent are discussed. We also discuss a relative lack of data from the African continent, the cost of specialised medication in resource-poor countries, and comorbidities of psoriatic arthritis. The lack of validated questionnaires relevant to the African continent is also important and discussed. Finally, we discuss a proposed research agenda that will improve care, quality of life, and outcomes for patients with psoriatic arthritis on the African continent.


[Mumps epidemic in the health area of Toledo with immunization intervention. Estimation of vaccine effectiveness].
The aim of this study was to describe a mumps epidemic occurred among school children in Toledo, Spain, between 1993 and 1994 were vaccination was undertaken as control measure, and to estimate vaccine efficacy under field conditions. Attack rates for vaccinated (at 15 months of age) and unvaccinated population were calculated. A retrospective cohort study was designed to estimate vaccine efficacy. A total of 19 outbreaks in different schools were declared. 216 cases and 4,059 contacts, between 10-17 years old, were investigated. The attack rate for the school population was 5.3%. By age, the highest attack rate was for those in the 12-13 age group (7.9%). Estimated vaccine efficacy was 76% (95% confidence interval 66-87%) for the whole study population: For children among 10-13 years old it was 87% (95% confidence interval 76-93%), and 46% (95% confidence interval 20-70%) for those aged 14-17 years. Vaccination is a good control measure in mumps outbreaks (the attack rate for the study population was 5.1%). Vaccine efficacy was high for the 10-13 age group and in agreement with the results of seroepidemiological studies.


Physicochemical studies of binary eutectic of ibuprofen and ketoprofen for enhanced transdermal drug delivery.
The thermodynamic, eutectic, and crystalline properties of ibuprofen and ketoprofen binary mixtures were investigated using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD). The DSC studies showed that melting point (61 degrees C), enthalpy (11.3 kJ/mol), and entropy of fusion (33.7 J/K/mol) of the binary eutectic were significantly lower than those of the individual anti-inflammatory drugs (NSAIDs). Due to the melting-point depression and enhanced skin lipid solubility, the steady-state flux of ibuprofen and ketoprofen from preparations of the binary eutectic increased as compared to pure NSAIDs using shed snakeskin as a model membrane. The NSAID membrane flux values were calculated by flux ratio equations based on drug thermodynamic data, and compared to experimental values obtained from permeation studies. The proposed flux ratio equations correctly predicted flux increase.


[The anatomical and histological investigation of the pancreas in the 19th century and till the discovery of insulin (1921). 4. The pancreas-research after the discovery of pancreas-diabetes (1889) till the discovery of insulin].
In this study is the history of the pancreas-research between 1889 and 1921 described. In this period are any important discoverys detected: The islets have 2 cell types (TSCHASSOW-NIKOW 1900, 1906); the connection between diabetes mellitus and islet-alterations (OPIE 1900); the independence of islets on exocrine parenchyma (SCHULZE 1900); the discovery of internal secretion (BAYLISS, STARLING 1902) and the regeneration of islets in mammals and the man (KYRLE 1908; WEICHSELBAUM 1908 in independent publications.


Light-assisted anticancer photodynamic therapy using porphyrin-doped nanoencapsulates.
Light activatable porphyrinic photosensitizers (PSs) are essential components of anticancer and antimicrobial therapy and diagnostic imaging. However, their biological applications are quite challenging due to the lack of hydrophilicity and biocompatibility. To overcome such drawbacks, photosensitizers can be doped into a biocompatible polymer such as gelatin and further can be used for biomedical applications. Herein, first, a novel A4 type porphyrin PS [5,10,15,20-tetrakis(4-pyridylamidephenyl)porphyrin; TPyAPP] was synthesized via a rational route with good yield. Further, this porphyrin was encapsulated into the gelatin nanoparticles (GNPs) to develop hydrophilic phototherapeutic nanoagents (PTNAs, A4por-GNPs). Notably, the synthesis of such porphyrin-doped GNPs avoids the use of any toxic chemicals or solvents. The nanoprobes have also shown good fluorescence quantum yield demonstrating their applicability in bioimaging. Further, the mechanistic aspects of the anticancer and antimicrobial efficacy of the developed A4por-GNPs were evaluated via singlet oxygen generation studies. Overall, our results indicated porphyrin-doped biodegradable polymeric nanoparticles act as effective phototherapeutic agents against a broad range of cancer cell lines and microbes upon activation by the low-cost LED light.


Raman spectrum, conformational stability, barriers to internal rotations and DFT calculations of 1,1,1-trifluoro-propane-2-thione with double-internal-symmetric rotor.
The Raman spectrum (3500-100 cm-1) of 1,1,1-trifluoro-propane-2-thione (TFPT), CF3C(S)CH3 of the solid phase has been recorded. The internal rotation of CH3 and/or CF3 moieties around CC bonds in TFPT allow five hypothetical conformers (Cs and C1 point groups). Aided by quantum chemical (QC) calculations, the Cc conformer is the only stable form (CF3 and CH3 groups are eclipsing the CS bond) which contains a planar FCC(S)CH backbone and possess intramolecular hydrogen sulfur interactions. However, other conformations (with the orientation of sulfur atom being trans to either hydrogen or fluorine atom) are either transition states or not fully converged geometry with "gauche" orientation. Moreover, the calculation were carried out at the level of Becke three Lee-Yan-Parr (B3LYP) parameters up to 6-311++G(d,p) basis sets. The torsional barriers are adequately described by a three-fold potential, V3 which have been determined utilizing the optimized structural parameters from the B3LYP/6-31G(d) basis set along with potential surface scan. Barriers of 1.28 kcal/mol (448 cm-1) and 1.94 kcal/mol (678 cm-1) were calculated for CH3 and CF3 symmetric rotors, respectively. Complete vibrational assignments have been reported for the stable Cc isomer which is supported by normal coordinate analysis and potential energy distributions (PEDs) for all fundamentals. Moreover, equilibrium geometries, vibrational frequencies are compared to the corresponding experimental values of acetone, 1,1,1-trifluoroacetone (TFA), hexafluoroacetone (HFA) and other molecules having the CF3 moiety whenever appropriate.


Enzyme-labeled DNA probes.
Many research workers and clinicians working in routine laboratories are now using the "tools" developed by molecular biologists over the past 10 years to produce DNA sequences that can be used as probes to detect specific genes. Thus it is possible to screen food for salmonella (1) or other organisms in a test much more quickly than conventional methods involving culturing the organisms. The presence of certain types of human papillomavirus in cervical smears can be used as an indicationof neoplasia (2). DNA probes can also be used to screen antenatally for diseases such as sickle cells anemia (3) or β°-thalassemia (4).


Retracted: Drop Height Impacts the Lower Limb Elastic Energy's Utilization for Male High Jumpers: A Experimental Research from Biomechanics.
[This retracts the article DOI: 10.1155/2022/8301477.].


Arylamides hybrids of two high-affinity σ2 receptor ligands as tools for the development of PET radiotracers.
1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) and 2-Methoxy-5-methyl-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)butyl]benzamide 2 (RHM-1) represent leads for tumor diagnosis, given their high affinity at σ(2) receptors. With the purpose of obtaining good candidates for σ(2) PET tracers development, hybrid structures between 1 and 2 were designed. Excellent σ(1)/σ(2) selectivities were reached when 6,7-dimethoxytetrahydroisoquinoline was linked to an o-methoxy substituted arylamide (11a, 12a, 15a), and for these benzamides an intramolecular H-bond in the active conformation at the σ sites, was hypothesized. However these excellent σ(2) ligands were accompanied by interaction with P-gp, which may limit their use as σ(2) receptor PET agents when tumors overexpress P-gp. Compound 15a whose P-gp interaction was just moderate represents an interesting tool for the development of σ(2) PET tracers useful in tumors overexpressing P-gp.


The atherogen 3-methylcholanthrene induces multiple DNA adducts in mouse aortic smooth muscle cells: role of cytochrome P4501B1.
3-Methylcholanthrene (MC), a polycylic aromatic hydrocarbon, induces atherogenesis in mice fed an atherogenic diet. In this study, we tested the hypothesis that MC would induce DNA adducts in mouse aortic smooth muscle cells (SMCs) and that cytochrome P4501B1 (CYP1B1) plays an important role in the activation of MC to genotoxic intermediates. Cultured SMCs were treated with MC or the vehicle dimethyl sulfoxide (DMSO), and DNA was isolated after 24 h. In some experiments, the cells were pre-treated with the CYP1B1 inhibitor 1-ethynylpyrene (EP) prior to exposure to MC. DNA adducts were determined by the 32P-postlabeling assay. Aryl hydrocarbon hydroxylase assay was measured by fluorimetry. MC induced formation of 12 DNA adducts that were not observed in DMSO-treated cells. DNA adduct formation was dose-dependent, with maximum response observed at 3 microM. Pre-treatment of cells with EP dramatically suppressed DNA adduct formation by MC. MC treatment caused induction of CYP1B1, but not CYP1A1. The induction of high levels of multiple DNA adducts in SMCs by MC suggests that SMCs have a functional enzymatic machinery capable of metabolically activating MC to genotoxic metabolites. The significant inhibition by EP of MC-induced DNA adduct formation indicated that CYP1B1 was the primary CYP enzyme responsible for formation of genotoxic metabolites that may play a role in the induction of atherosclerosis by MC.


Influences of industrial development and urbanization on human lives in premodern Japan: Views from paleodemography.
This study tests the hypothesis that industrial development and urbanization negatively impacted the living circumstances and health of inhabitants. The materials used in this study included 881 human skeletons aged 15 years and older from the Medieval (1185-1573), Edo (1603-1867), and Meiji (1868-1912) periods. The Meiji period corresponds to the period when the industrial revolution spread in Japan. Age at death and sex were estimated for each skeleton, and demographic profiles of the Medieval, Edo, and Meiji periods were compared. The rate of young deaths was higher in the Meiji period than in preceding periods, and urban inhabitants had a higher proportion of young deaths than rural inhabitants in the Edo period. The results suggest that industrial development and urbanization led to a decline in human health. The results produced through Bayesian methods are likely tentative, because they vary according to the priors and reference sample. Paleodemographic approaches are a useful method to elucidate the impact of industrialization and urbanization on health. Decline of health associated with industrialization should be examined combining paleopathological and paleodemographic methods.


Effects of Acid-Reducing Agents on the Pharmacokinetics of Lazertinib in Patients with EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer.
Lazertinib is an irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Co-administration of TKIs with acid-reducing agents (ARAs) can lead to potential drug-drug interactions, which decreases solubility and absorption of TKIs and is ultimately associated with reduced efficacy of TKIs. This retrospective analysis evaluated the effect of ARAs on the pharmacokinetics of lazertinib using data obtained from patients with advanced EGFR mutation-positive non-small-cell lung cancer. In a total of 234 patients with lazertinib pharmacokinetics observed at steady state, dose-normalized (DN) area under the concentration-time curve (AUCss), maximum concentration (Cmax,ss), and/or trough concentration on day 15 (CD15) were compared between a group receiving ARA concomitantly for at least 4 days (ARA group) and another group not receiving ARA (non-ARA group) in a dose-proportional range. Additionally, a comparison of pharmacokinetic parameters at a therapeutic dose of 240 mg once daily was evaluated. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) of ARA group to non-ARA group for DNAUCss, DNCmax,ss, and DNCD15 at 40 mg to 320 mg once daily showing the dose proportionality were 0.8743 (0.7285-1.0493), 0.9035 (0.7482-1.0910), and 0.9126 (0.7364-1.1311), respectively. GMRs with 90% CIs for AUCss, Cmax,ss, and CD15 at 240 mg were 0.9136 (0.6637-1.2576), 0.9012 (0.6703-1.2116), and 0.8850 (0.6463-1.2118), respectively. All pharmacokinetic parameters were not significantly different between the two groups (p values > 0.05), indicating that co-administered ARAs did not significantly affect the steady state pharmacokinetics of lazertinib. Therefore, no dose adjustment of lazertinib is required in patients receiving concomitant ARAs. NCT03046992, NCT04075396.


Improving the quality and appeal of pureed meals for patients.
This article describes how a critical incident led to a review of the pureed diet options offered to patients within a hospital setting. This resulted in significant changes within the trust, improving both the nutritional content and the appeal of the pureed diet menu.


Light-Modulated Self-Blockage of a Urea Binding Site in a Stiff-Stilbene Based Anion Receptor.
Anion binding to a receptor based on stiff-stilbene, which is equipped with a urea hydrogen bond donating group and a phosphate or phosphinate hydrogen bond accepting group, can be controlled by light. In one photoaddressable state (E isomer) the urea binding site is available for binding, while in the other (Z isomer) it is blocked because of an intramolecular interaction with its hydrogen bond accepting motif. This intramolecular interaction is supported by DFT calculations and 1 H NMR titrations reveal a significantly lower anion binding strength for the state in which anion binding is blocked. Furthermore, the molecular switching process has been studied in detail by UV/Vis and NMR spectroscopy. The presented approach opens up new opportunities toward the development of photoresponsive anion receptors.


Health risk associated with dietary co-exposure to high levels of antimony and arsenic in the world's largest antimony mine area.
Like arsenic (As), antimony (Sb) is known to be a genotoxic element in vitro and in vivo. Sb is now recognized as a global contaminant and has aroused the global concerns recently. However, knowledge is scarce concerning the transfer of Sb from the environment to humans and the related hazards to human health. In this pilot study, the health risk and main pathway of long-term human exposure to Sb and As for residents around Chinese Xikuangshan (XKS) Sb mine, the world's largest Sb mine, were evaluated by dietary exposure and hair accumulations survey. The concentrations and species of Sb and As in food samples (n=209) from three main categories and six subcategories, and in hair samples (n=89) were determined. Residents in the vicinity of XKS had an estimated dietary intake of Sb (554 μg/day) which was 1.5 times higher than the tolerable daily intake (TDI) (Sb, 360 μg/day), whereas their dietary intake of inorganic As (107 μg/day) was slightly lower than the provisional tolerable weekly intake (PTWI) of 15 μg/kg BW/week (equal to 129 μg As/day). Hair Sb and As concentrations (Sb, 15.7 mg/kg, DW; As, 3.99 mg/kg, DW) in XKS residents are both above the normal/toxic level. Rice, vegetables (especially leafy vegetable), drinking water, and meat/poultry were the dominant dietary intake sources of Sb for the residents. In contrast, rice was the uniquely dominant dietary intake source of As. Antimonate (Sb(V)) was the dominant Sb species in vegetables, drinking water and residents' hairs. This study highlighted the difference of exposure characteristics between Sb and As. The preliminary results suggested that dietary exposures to Sb, rather than As, was the dominant health risk to local residents. Nevertheless, the adverse effects of As levels on the health of residents still can not be ignored since the elevated As concentrations in human hair have reached the critical level for health risks. In addition, this pilot study did not consider the possible Sb and As combined effects.


Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.
Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.


A new birthweight reference in Guangzhou, southern China, and its comparison with the global reference.
To formulate a new birthweight reference for different gestational ages in Guangzhou, southern China, and compare it with the currently used reference in China and the global reference. All singleton live births of more than 26 weeks' gestational age recorded in the Guangzhou Perinatal Health Care and Delivery Surveillance System for the years 2009, 2010 and 2011 (n=510 837) were retrospectively included in the study. In addition, the study sample was supplemented by all singleton live births (n=3538) at gestational ages 26-33 weeks from 2007 and 2008. We used Gaussian mixture models and robust regression to exclude outliers of birth weight and then applied Generalized Additive Models for Location, Scale, and Shape (GAMLSS) to generate smoothed percentile curves separately for gender and parity. Of infants defined as small for gestational age (SGA) in the new reference, 15.3-47.7% (depending on gestational age) were considered appropriate for gestational age (AGA) by the currently used reference of China. Of the infants defined as SGA by the new reference, 9.2% with gestational ages 34-36 weeks and 14.3% with 37-41 weeks were considered AGA by the global reference. At the 50th centile line, the new reference curve was similar to that of the global reference for gestational ages 26-33 weeks and above the global reference for 34-40 weeks. The new birthweight reference based on birthweight data for neonates in Guangzhou, China, differs from the reference currently used in China and the global reference, and appears to be more relevant to the local population.


Stem cells in the treatment of cardiovascular disease--an overview.
CVD irreversibly damage the cardiomyocytes, the heart muscle cells. This loss triggers a cascade of detrimental events, including formation of scar tissue, an overload of blood flow and pressure capacity, the overstretching of viable cardiac cells, leading to heart failure and eventual death. Restoring damaged heart muscle tissue, through repair or regeneration, is a potentially new strategy to treat heart failure and various other CVD. Stem cells are promising new therapeutics for patients with different heart diseases. The remarkable proliferative and differentiation capacity of stem cells promises an unlimited supply of specific cell types including viable functioning heart muscle cells. A crucial issue in designing more rational cell-based therapy approaches for cardiac disease is understanding the mechanisms by which each of the stem cell or progenitor-cell types can affect myocardial performance. This paper will highlight findings of multiple preliminary clinical experiments involving stem cells as therapeutics, educate the reader on the incidence and prevalence of CVD, the risk factors associated with CVD, and explore some of the challenges that can be encountered.


MHC class II variation in the endangered European mink Mustela lutreola (L. 1761)--consequences for species conservation.
The polymorphic major histocompatibility complex (MHC) has gained a specific relevance in pathogen resistance and mate choice. Particularly the antigen-binding site (ABS), encoded by exon 2 of the DRB class II gene, exhibits numerous alleles and extensive sequence variations between alleles. A lack of MHC variability has attributed to instances such as bottleneck effects or relaxed selection pressure and has a certain impact on the long-term viability of the species concerned. As a result of seriously decreased population density during the last century, the current population of the endangered European mink (Mustela lutreola, L. 1761) has suffered from geographic isolation. In this study, we amplified a partial sequence of the MHC class II DRB exon 2 (229 bp), assessed the degree of genetic variation and compared the variability with those of other Mustelidae. As a result, nine alleles were detected in 20 investigated individuals, which differ from each other by four to 25 nucleotide substitutions (two to 11 amino acid substitutions). Whilst an equal ratio for synonymous and non-synonymous substitutions was found inside the ABS, synonymous substitutions were significantly higher than non-synonymous substitutions in the non-ABS region. Results might indicate that no positive selection exists within the ex situ population of M. lutreola, at least in the analysed fragment. In addition, phylogenetic analyses support the trans-species model of evolution.


Treatment of stage D prostatic carcinoma with megestrol acetate.
Nine previously untreated patients with stage D prostatic carcinoma received megestrol acetate 40 mg orally three times daily. Responses included five partial regressions, two stabilizations, and two progressions. Duration of response ranged from 3+ to 33+ months, with a mean of 11.7 months and a median of 12 months. Three of five patients who had failed prior hormonal therapy remained objectively stable while receiving megestrol acetate. No gastrointestinal toxicity, gynecomastia, fluid retention, or thromboembolic complications were observed during treatment. Weight gain of 5 to 51 pounds occurred in seven of 14 patients.


Isolated MPTL reconstruction fails to restore lateral patellar stability when compared to MPFL reconstruction.
To biomechanically evaluate MPTL reconstruction and compare it with two techniques for MPFL reconstruction in regard to changes in patellofemoral contact pressures and restoration of patellar stability. This is an experimental laboratory study in eight human cadaveric knees. None had patellofemoral cartilage lesions or trochlear dysplasia as evaluated by conventional radiographs and MRI examinations. The specimens were secured in a testing apparatus, and the quadriceps was tensioned in line with the femoral shaft. Contact pressures were measured using the TekScan sensor at 30°, 60° and 90°. The sensor was placed in the patellofemoral joint through a proximal approach between femoral shaft and quadriceps tendon to not violate the medial and lateral patellofemoral complex. TekScan data were analysed to determine mean contact pressures on the medial and lateral patellar facets. Patellar lateral displacement was evaluated with the knee positioned at 30° of flexion and 9 N of quadriceps load, then a lateral force of 22 N was applied. The same protocol was used for each condition: native, medial patellofemoral complex lesion, medial patellofemoral ligament reconstruction (MPFL-R) using gracilis tendon, MPFL-R using quadriceps tendon transfer, and medial patellotibial ligament reconstruction (MPTL-R) using patellar tendon transfer. No statistical differences were found for mean and peak contact pressures, medial or lateral, among all three techniques. However, while both techniques of MPFL-R were able to restore the medial restraint, MPTL-R failed to restore resistance to lateral patellar translation to the native state (mean lateralization of the patella [mm]: native: 9.4; lesion: 22; gracilis MPFL-R: 8.1; quadriceps MPFL-R: 11.3; MPTL-R: 23.4 (p < 0.001). MPTL-R and both techniques for MPFL-R did not increase patellofemoral contact pressures; however, MPTL-R failed to provide a sufficient restraint against lateral patellar translation lateral translation in 30° of flexion. It, therefore, cannot be recommended as an isolated procedure for the treatment of patellar instability.


Prion protein gene polymorphism and genetic risk evaluation for scrapie in all Turkish native sheep breeds.
The aim of this study was to identify the prion protein (PrP) gene polymorphism in a total of 1,110 healthy sheep from 18 Turkish native sheep breeds. There were nine alleles and 22 genotypes observed based on codons 136, 154, and 171 of the PrP gene. The ARQ allele was predominant for all breeds. The most resistant allele to scrapie, ARR, was present in all breeds. The VRQ allele, associated with the highest susceptibility to scrapie, was detected at low frequencies in İvesi (0.06), Kıvırcık (0.021), Sakız (0.010), Karayaka (0.011), Çine Çaparı (0.012), and Güneykaraman (0.017). In general, the ARQ/ARQ genotype was predominant in all breeds. The most resistant genotype to scrapie, ARR/ARR, was found with the frequency lower than 0.180. The most susceptible genotype, VRQ/VRQ, was found in only Kıvırcık. The TRR and TRH alleles and the genotypes of ARR/TRR, ARR/ARK, and ARH/TRH have been found for the first time in Turkish native sheep breeds. According to these results, all breeds belong to risk group R3 followed by R2. It is propounded that the susceptibility to scrapie increased from eastern to western part of Turkey. Our findings of Turkish native sheep breeds with PrP gene polymorphisms will assist the sheep breeding program for selection of scrapie resistance genotypes to reduce the risk of scrapie.


Aerogels based on cationically modified chitosan and poly(vinyl alcohol) for efficient capturing of viruses.
In this study, we developed a new filtering bioaerogel based on linear polyvinyl alcohol (PVA) and the cationic derivative of chitosan (N-[(2-hydroxy-3-trimethylamine) propyl] chitosan chloride, HTCC) with a potential antiviral application. A strong intermolecular network architecture was formed thanks to the introduction of linear PVA chains, which can efficiently interpenetrate the glutaraldehyde(GA)-crosslinked HTCC chains. The morphology of the obtained structures was examined using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The aerogels and modified polymers' elemental composition (including the chemical environment) was determined using X-ray photoelectron spectroscopy (XPS). New aerogels with more than twice as much developed micro- and mesopore space and BET-specific surface area were obtained concerning the starting sample chitosan aerogel crosslinked by glutaraldehyde (Chit/GA). The results obtained from the XPS analysis showed the presence of cationic 3-trimethylammonium groups on the surface of the aerogel, which can interact with viral capsid proteins. No cytotoxic effect of HTCC/GA/PVA aerogel was also observed on fibroblast cells of the NIH3T3 line. Furthermore, the HTCC/GA/PVA aerogel has been shown that efficiently traps mouse hepatitis virus (MHV) from suspension. The presented concept of aerogel filters for virus capture based on modified chitosan and polyvinyl alcohol has a high application potential.


Incidence rate of metastases in the oral cavity: a review of all metastatic lesions in the oral cavity.
Metastases in the oral cavity are rare and account for only 1 to 3% of all malignant lesions in this area. The primary location from which most metastases have been described in the oral cavity in adult patients include lungs, breasts, kidneys and colon. A systematic search of the literature was carried out following the PRISMA statement in PubMed database. Clinical trials and case series published in the last 10 years [2010-2020] were eligible to be selected. The headings and keywords used in the searches were "cancer" AND "oral metastases", "incidence" AND "oral metastases", "oral metastases" AND "jaw bone", "oral metastases" AND "soft tissue". For the study of the incidence of metastases in the oral cavity, 9 reports of clinical trials and 7 retrospective studies of case series have been included in this article. The primary locations from which more metastases have been described in the oral cavity are lungs (30.6% or 183 cases), breasts (22.2% or 133 cases), liver (15.5% or 93 cases), prostate (9 % or 54 cases), thyroid glands (8.1% or 49 cases), kidneys (7.3% or 44 cases), skin (2.3% or 14 cases), soft tissues (2% or 12 cases), colon (2% or 12 cases) and gastrointestinal (0.6% or 4 cases). These metastases have a predilection for hard tissues. The clinical presentation of these lesions varies from painless granulomatous lesions to lytic areas in the jaws. Although metastases in the oral cavity is an uncommon pathology, early diagnosis is needed so that in the event that it is the first manifestation, it allows the primary tumor to be diagnosed as soon as possible.


Distribution and excretion of 2,2',3,4',5,5',6-heptachlorobiphenyl (CB187) and its metabolites in rats and guinea pigs.
4-Hydroxy (OH)-2,2',3,4',5,5',6-heptachlorobiphenyl (CB187) is a polychlorinated biphenyl (PCB) metabolite present in human serum at the highest concentration of the PCB metabolites. Our previous study demonstrated that CB187 was metabolized by rat and guinea pig liver microsomes to the major metabolite 4'-OH-2,2',3,3',5,5',6-heptachlorobiphenyl (CB178), and the two minor metabolites 4-OH-CB187 and 4'-OH-2,2',3,5,5',6-hexachlorobiphenyl (CB151). In this study, the distribution of these metabolites in serum, liver and kidney, and their fecal excretion, were examined in rats and guinea pigs intraperitoneally dosed with CB187. Similarly to the in vitro study, 4'-OH-CB178 was a major metabolite in the liver, serum and feces of both animal species on day 4 after CB187 injection, and the level in the liver was about 20 times higher in untreated guinea pigs than in untreated rats. In addition, 4-OH-CB187, a minor metabolite, was detected in the serum and kidneys, but not in the feces, of both guinea pigs and rats. Another minor metabolite, 4'-OH-CB151, was detected at a lower level only in guinea pig feces; little was found in the serum or liver of either animals. Over the 30d following CB187 injection into guinea pigs, 4'-OH-CB178 and 4-OH-CB187 in the serum was observed at higher level on day 4 and day 16 after injection, respectively. The majority of the 4'-OH-CB178 was rapidly excreted to the feces following unmetabolized CB187, whereas 4-OH-CB187 was not found in guinea pig feces and liver during 30d. These results support previous reports that 4-OH-CB187 is retained persistently in animal blood.


Real-Time Cell Migration Monitoring to Analyze Drug Synergism in the Scratch Assay Using the IncuCyte System.
Drug-mediated interference with metastasis represents a key approach to improve cancer therapy. In this regard, appropriate in vitro assays are needed to identify drugs, which inhibit cell migration as one feature for metastatic potential of cancer cells. One such migration assay is the wound healing or scratch assay, designed to allow cells for closure of an artificially generated gap (wound/scratch) in the monolayer. To identify possibly effective anti-migratory drugs as monotherapy or as synergistic drug combination, novel screening tools besides viability measurements at the experimental endpoint are needed. In this context, particularly drug combinations allow to increase treatment efficacy paralleled by lowered side effects. Here, a protocol for real-time monitoring cellular motility and its inhibition by anti-migratory drugs and combinations by the IncuCyte system and a 96-well scratch assay is described. A pipetting scheme allowing data collection for synergy calculation using one plate per replicate is provided. Using the IncuCyte System 2, drug combinations built of three biological replicates each using three technical replicates can be tested in parallel within hours to few days to accelerate identification of efficient antimetastatic drugs.


Metatarsal pain and plantar hyperkeratosis in the forefeet of female professional flamenco dancers.
The objectives of this study were to determine the frequency of metatarsal pain and of hyperkeratosis on the plantar forefoot in female professional flamenco dancers, and to determine whether there is a relationship between the two disorders. Forty-four female professional flamenco dancers, with a minimum activity of 25 hrs/wk, participated in this cross-sectional study. The presence or absence of metatarsal pain while dancing was recorded, and plantar pressures were measured on a pressure platform, both barefoot and shod with the usual dance shoe. The heel height of the dance shoe was also measured. Of the dancers, 80.7% experienced metatarsal pain while dancing, and 84.1% presented with plantar hyperkeratosis. Plantar hyperkeratosis coincided with the presence of metatarsal pain in 67.04% of the feet studied. The maximum load point in the feet when the dancers were barefoot was located 59.5% in the rearfoot and 40.5% in the forefoot; when dancers wore their specific flamenco dancing shoes, it was located 52.4% in the rearfoot and 47.6% in the forefoot. Metatarsal pain and plantar hyperkeratosis in the forefoot are common foot disorders in female flamenco dancing. The incidence of the maximum load point being located in the forefoot, and the difference between the results of the tests while shod or barefoot, are both too low to support the idea that the raised heels of flamenco shoes are a major contributing factor for these injuries. Therefore, these disorders may be caused by chronic repetitive trauma suffered during the practice of footwork dancing.


The effect of glycerol treatment on crab muscle fibres.
1. Membrane constants of the closer muscle of the ghost crab, Ocypoda cursor, were determined before and after treatment in hypertonic glycerol solution and return to an artificial sea-water (A.S.W.) solution.2. Muscle contraction was abolished after return of the muscle to A.S.W.3. The membrane capacitance was reduced from 29.0 muF/cm(2) to 10.5 muF/cm(2).4. Other passive properties of the muscle membrane, not dependent on capacitance, were not changed.5. The presynaptic nerve, transmitter release, post-synaptic sensitivity to transmitter and ionic mechanisms of synaptic action were unaffected by glycerol treatment.6. More than 60% of the membrane capacitance/unit area is contributed by the complex tubular system.7. The tubular system in crustacea is necessary for excitation-contraction coupling.


An investigation into the suitability of using three electronic nose instruments for the detection and discrimination of bacteria types.
The use of electronic nose (e-nose) technology for detection of food-borne bacteria has several practical advantages over current laboratory procedures, such as lower cost and reduced testing time. In this work, we are interested in using electronic nose systems to detect E. coli and Listeria in a nutrient broth, and discriminate between these bacteria types at various concentrations. To do this, we use instruments based on three different technologies - fingerprint mass spectrometry, metal oxide sensors, and conductive polymer sensors. Our results indicate that separation between groups can be achieved. We describe the relative merits and drawbacks of each technology and discuss how this rich multimodal dataset can be used to build a classification system.


The Avian Diet Database as a source of quantitative information on bird diets.
This data paper describes a compilation of 73,075 quantitative diet data records for 759 primarily North American bird species, providing standardized information not just on the diet itself, but on the context for that diet information including the year, season, location, and habitat type of each study. The methods used for collecting and cleaning these data are described, and we present tools for summarizing and visualizing diet information by bird species or prey.