Nodular lymphoid disease of the head and neck: lymphocytoma cutis, benign lymphocytic infiltrate of Jessner, and their distinction from malignant lymphoma.
Skin biopsy specimens from six patients with nodular lymphoid disease of the head and neck were studied by routine histology, direct immunofluorescence microscopy, and leukocyte monoclonal antibodies to T and B cell subsets and monocytes. Initially, these lesions were clinically considered to be benign lymphocytic infiltrates of Jessner, lymphocytoma, or lymphoma. Direct immunofluorescence was negative or showed nonspecific staining in all four patients in whom it was performed. Leukocyte monoclonal antibody stains revealed two distinct patterns of lymphocytes. Lymphocytoma was represented by nodular masses of B lymphocytes with peripheral and intervening zones of T cells. The second pattern consisted of solid nodular masses of T lymphocytes occupying the dermis and subcutaneous tissue. In the specimens interpreted as benign lymphocytic infiltration, the T cells were composed equally of helper and suppressor cells.


[Risk of gastric cancer dependent on serological markers of atrophic gastritis: cohort study].
In a prospective study the risk of subsequent gastric cancer (GC) was assessed in persons aged 45-69 over 5 years after the initial testing with a set of serological tests (pepsinogen I, pepsinogen II, gastrin-17, antibodies to Helicobacter pylori). The presence of gastric atrophy markers was a significant predictor of GC in the forthcoming years. Non-invasive techniques may be used in the formation of high-risk groups, followed by GC active surveillance.


R-R interval-based sleep apnea screening by a recurrent neural network in a large clinical polysomnography dataset.
Easily detecting patients with undiagnosed sleep apnea syndrome (SAS) requires a home-use SAS screening system. In this study, we validate a previously developed SAS screening methodology using a large clinical polysomnography (PSG) dataset (N = 938). We combined R-R interval (RRI) and long short-term memory (LSTM), a type of recurrent neural networks, and created a model to discriminate respiratory conditions using the training dataset (N = 468). Its performance was validated using the validation dataset (N = 470). Our method screened patients with severe SAS (apnea hypopnea index; AHI ≥ 30) with an area under the curve (AUC) of 0.92, a sensitivity of 0.80, and a specificity of 0.84. In addition, the model screened patients with moderate/severe SAS (AHI ≥ 15) with an AUC of 0.89, a sensitivity of 0.75, and a specificity of 0.87. Our method achieved high screening performance when applied to a large clinical dataset. Our method can help realize an easy-to-use SAS screening system because RRI data can be easily measured with a wearable heart rate sensor. It has been validated on a large dataset including subjects with various backgrounds and is expected to perform well in real-world clinical practice.


Increase in brown adipose tissue activity after weight loss in morbidly obese subjects.
Stimulation of thermogenesis in brown adipose tissue (BAT) is a potential target to treat obesity. We earlier demonstrated that BAT activity is relatively low in obese subjects. It is unknown whether BAT can be recruited in adult humans. To study the dynamics of BAT, we observed BAT activity in morbidly obese subjects before and after weight loss induced by bariatric surgery. This was an observational prospective cohort study. The study was conducted at a referral center. Ten morbidly obese subjects eligible for laparoscopic adjustable gastric banding surgery were studied before and 1 yr after bariatric surgery. The main outcome measure was BAT activity, as determined after acute cold stimulation using (18)F-fluorodeoxyglucose positron emission tomography and computed tomography. Before surgery, only two of 10 subjects showed active BAT. One year after surgery, the number of subjects with active BAT was increased to five. After weight loss, BAT-positive subjects had significantly higher nonshivering thermogenesis compared with BAT-negative subjects (P < 0.05). The results show that in humans BAT can be recruited in the regions in which it was also reported in lean subjects before. These results for the first time show recruitment of BAT in humans and may open the door for BAT-targeted treatments of obesity.


Intrinsic factor secretion from isolated human gastric mucosal cells.
Human gastric mucosal cells were isolated from the resected fundic mucosa of peptic ulcer patients. The intracellular content and secretion of intrinsic factor were estimated by binding to cyano[57Co]cobalamin. The content was maximal in the enriched parietal cell fraction which also displayed the highest H+ production as measured by amino[14C] pyrine uptake. Secretagogues evoked full response after 15 min of incubation: pentagastrin (181% of basal secretion), carbachol (208%), histamine (250%) and dibutyryl cyclic adenosine monophosphate (304%). The phosphodiesterase inhibitor isobutylmethylxanthine was slightly more effective even than dibutyryl cAMP. The response to histamine was abolished by ranitidine, indicating activation of adenylate cyclase via histamine H2 receptors, but remained unaffected by atropine, which in turn blocked the carbachol effect, whereas ranitidine was ineffective. The mean formation rate was 8.4 fmol intrinsic factor/10(6) cells per h under basal conditions and 14.3 fmol in response to histamine.


Identification and comparison of metabolites after oral administration of essential oil of Ligusticum chuanxiong or its major constituent ligustilide in rats.
The rhizome of Ligusticum chuanxiong Hort. is a well-known traditional Chinese medicinal herb that is widely used to treat various vascular diseases. The aims of this study were to identify and compare the metabolites in rats after the oral administration of the essential oil of Ligusticum chuanxiong Hort. or its major constituent ligustilide monomer, and to explore the differences in the metabolism of the main active constituent monomer and the active constituent group. High-performance liquid chromatography with diode array detection was used to analyze the metabolites in the urine, feces, and bile of rats dosed with the essential oil or ligustilide. We observed clear differences in the metabolism of the essential oil and ligustilide. The other chemical constituents in the essential oil influenced the metabolism of the main active constituent monomer. Four metabolites in urine were separated, purified, and identified as 6,7-dihydro-6,7-dihydroxyligustilide (M1), 3,5-dihydroxy-3-butylphthalide (M2), 6,7-dihydro-6-hydroxy-7-sulfmethylligustilide (M3), and 5-hydroxy-3-butylidenephthalide (M4) by FT-ICR-MS and 1H-NMR. M2 and M3 are novel metabolites. Based on the profiles of these metabolites, the pathway of ligustilide metabolism in rats is proposed.


Comparison of static and dynamic symmetry between masseter-innervated and dual-innervated free multivector serratus anterior muscle transfer for complete facial paralysis.
In this study, facial symmetry was compared between the masseter-innervated and dual-innervated free multivector serratus anterior muscle transfer (FMSAMT) methods. Eighteen patients with unilateral complete facial paralysis underwent facial reanimation surgery between April 2006 and July 2019. The masseter-innervated FMSAMT group (Group M, n = 8) underwent end-to-end coaptation with the ipsilateral masseter nerve in one stage. The dual-innervated FMSAMT group (Group D, n = 10) underwent end-to-end coaptation with the masseter nerve and end-to-side coaptation with the contralateral facial nerve via cross-face nerve graft. They were further divided into the one-stage (Group D1, n = 5) and two-stage (Group D2, n = 5) subgroups. The durations of periods until the first visible muscle contraction with clenching, first spontaneous smile, and the completion of resting tone were evaluated. The possibility of a spontaneous smile and symmetry of the midline and horizontal deviation at rest and during voluntary smiling were compared between each group. Groups M and D differed significantly in the possibility of a spontaneous smile and improvement rate of midline deviation and horizontal deviation at rest (p < 0.001, p < 0.001, and p = 0.001, respectively) but not in the improvement rate of midline and horizontal deviation during voluntary smiling. The duration of the period until the completion of resting tone was significantly shorter in Group D1 than in Group D2 (p = 0.048); however, the possibility of a spontaneous smile and the improvement rate of midline and horizontal deviation were not significantly different. Dual-innervated FMSAMT was effective in guaranteeing a symmetrical resting tone, voluntary smiling, and reproducing a spontaneous smile.


Propofol attenuates inflammatory response and apoptosis to protect d-galactosamine/lipopolysaccharide induced acute liver injury via regulating TLR4/NF-κB/NLRP3 pathway.
Propofol has been reported to be protective against liver injury due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. The purpose of this study was to examine the protective effects of propofol on d-galactosamine/lipopolysaccharide (d-GalN/LPS) induced acute liver injury. Mice were given an intraperitoneal injection of propofol before d-GalN/LPS treatment. Liver injury was confirmed by serum biochemical analysis and liver histopathological analysis. Relevant molecular events were determined by ELISA, western blot, and test kits. Cell apoptosis were evaluated by TUNEL assay. The results showed that propofol significantly prevented d-GalN/LPS-induced liver damage by preventing associated increases of serum alanine transaminase (ALT) and aspartate transaminase (AST) and restoring liver histopathological changes. Propofol markedly inhibited the production of inflammatory cytokines and oxidative stress-related factors. Propofol markedly reduced hepatocyte apoptosis, decreased Bax, Bad, cleaved caspase-3 and increased Bcl-2 expression. Besides, NLRP3 inflammasome and TLR4/NF-κB pathway were inactivated under the treatment of propofol according to the expression of pathways-related proteins. Taken together, propofol contributed to liver protection against d-GalN/LPS-induced liver injury in mice by inhibiting inflammation, oxidative stress and hepatocyte apoptosis through regulating TLR4/NF-κB/NLRP3 pathway.


Local formalin instillation: an effective treatment for uncontrolled radiation-induced hemorrhagic proctitis.
The aim of this study was to evaluate the efficacy of local instillation of 4% formalin in the management of uncontrolled radiation-induced and ischemic hemorrhagic proctitis. Eight patients were reviewed. Operation characteristics, morbidity and long-term results were analyzed. All patients were followed for a median of 18 months. In 5 patients the bleeding stopped after a single treatment and in 3 after a second one. During follow-up no recurrent rectal bleeding occurred, no further medical treatment was needed and in all patients the complaints had disappeared. Local instillation of 4% formalin is an effective treatment for uncontrolled radiation-induced and ischemic hemorrhagic proctitis.


Immunotherapy in head and neck cancer: The great challenge of patient selection.
The development of immune checkpoint inhibitors (ICIs) revolutionized the therapeutic landscape in head and neck cancer. However, the majority of patients present primary resistance to ICIs and do not benefit from use of these agents, highlighting the need of developing predictive biomarkers to better determine who will benefit from treatment with ICIs. Patient's related clinical characteristics, disease related features, pathological and molecular factors, as well as emerging immune predictive biomarkers can be considered for the selection of those patients who would be the best candidate for immunotherapy. We examined these factors, emerging from the results of currently available studies in head and neck squamous cell carcinoma (HNSCC), in order to provide a useful tool which could assist the oncologist in their clinical practice.


Prediction of risk factors for first trimester pregnancy loss in frozen-thawed good-quality embryo transfer cycles using machine learning algorithms.
Can the risk factors that cause first trimester pregnancy loss in good-quality frozen-thawed embryo transfer (FET) cycles be predicted using machine learning algorithms? This is a retrospective cohort study conducted at Sisli Memorial Hospital, ART and Reproductive Genetics Center, between January 2011 and May 2021. A total of 3805 good-quality FET cycles were included in the study. First trimester pregnancy loss rates were evaluated according to female age, paternal age, body mass index (BMI), diagnosis of infertility, endometrial preparation protocols (natural/artificial), embryo quality (top/good), presence of polycystic ovarian syndrome (PCOS), history of recurrent pregnancy loss (RPL), recurrent implantation failure (RIF), severe male infertility, adenomyosis and endometriosis. The first trimester pregnancy loss rate was 18.2% (693/ 3805). The presence of RPL increased first trimester pregnancy loss (OR = 7.729, 95%CI = 5.908-10.142, P = 0.000). BMI, which is > 30, increased first trimester pregnancy loss compared to < 25 (OR = 1.418, 95%CI = 1.025-1.950, P = 0.033). Endometrial preparation with artificial cycle increased first trimester pregnancy loss compared to natural cycle (OR = 2.101, 95%CI = 1.630-2.723, P = 0.000). Female age, which is 35-37, increased first trimester pregnancy loss compared to < 30 (OR = 1.617, 95%CI = 1.120-2.316, P = 0.018), and female age, which is > 37, increased first trimester pregnancy loss compared to < 30 (OR = 2.286, 95%CI = 1.146-4,38, P = 0.016). The presence of PCOS increased first trimester pregnancy loss (OR = 1.693, 95%CI = 1.198-2.390, P = 0.002). The number of previous IVF cycles, which is > 3, increased first trimester pregnancy loss compared to < 3 (OR = 2.182, 95%CI = 1.708-2.790, P = 0.000). History of RPL, RIF, advanced female age, presence of PCOS, and high BMI (> 30 kg/m2) were the factors that increased first trimester pregnancy loss.


Citral Inhibition of Human Salivary Aldehyde Dehydrogenase.
Human salivary aldehyde dehydrogenase (hsALDH) protects us from the toxic effect of aldehydes. It has both diagnostic and therapeutic importance. Citral possesses many biological and pharmacological properties. The aim of this work was to investigate the inhibitory effect and the mechanism of inhibition of citral on hsALDH. Citral inhibits the dehydrogenase activity of hsALDH. It decreased the substrate affinity and to a lesser extent, the catalytic efficiency of hsALDH. Citral showed linear mixed-type inhibition with a higher tendency of competitive behavior with little, but significant, non-competitive inhibition. The nucleophilicity of active site Cys residue is not a significant contributing factor in the inhibition process. Citral shows uncompetitive inhibition towards the co-enzyme (NAD+). α-helix and β-sheet content of the enzyme were changed in presence of citral. Biophysical studies showed that citral quenches the intrinsic fluorescence of hsALDH in a static manner by forming complex with the enzyme. Molecular docking study showed that both the isomers of citral bind to the catalytic site of hsALDH interacting with few evolutionary preserved amino acid residues through multiple non-covalent interactions. Ligand efficiency metrics values indicate that citral is an efficient ligand for the enzyme in terms of its physicochemical and pharmacokinetic properties.


Whole-body hyperthermia in cancer therapy: a report of a phase I-II study.
Twenty-seven patients were treated with whole-body hyperthermia alone or in combination with either chemotherapy or radiotherapy. Whole-body hyperthermia was performed in the Pomp-Siemens cabin with hot air and a warm water mattress, the patient being covered with plastic film to avoid cooling by perspiration. The heat treatment lasted for 2 hr at 41.8-42.0 degrees C. Toxicity, such as liver damage and respiratory problems, was considerable. There were two fatalities. Hyperthermia gave an improved therapeutic effect in 6 of the patients. Considerable pain relief was observed in 8 of 10 patients. Whole-body hyperthermia at 42 degrees C can be effective but the potential toxicity limits its use to those patients with severe complaints for whom no other palliative treatment is available.


Regulation of photosynthetic carbon assimilation.
It may be concluded that the conversion of PGA to DPGA plays a key role in induction and in the regulation of cycle activity. The high concentrations of PGA in actively photosynthesizing chloroplasts reflect this role and the control exerted by adenylate ratios. Thus the cycle can operate at its maximum rate only in the presence of high PGA and low ribulose 5-phosphate concentrations. Once induction is complete, the reductive pentose phosphate pathway will continue to function at its maximum rate if sink activity within the cytoplasm makes available sufficient Pi to support rapid export of triose phosphate. If triose phosphate tends to build up in the straoma, it will favor pentose monophosphate accumulation. A relative excess of ribulose 5-phosphate would, in turn, inhibit PGA reduction (and hence its own formation) by drawing too heavily on the available ATP.


Fluxapyroxad disrupt erythropoiesis in zebrafish (Danio rerio) embryos.
Fluxapyroxad, a succinate dehydrogenase inhibitor (SDHI) fungicide, is commercialized worldwide to control a variety of fungal diseases. Growing evidence shows that fluxapyroxad is teratogenic to aquatic organisms. In this study, the influence of fluxapyroxad toward hematopoietic development was evaluated using zebrafish embryos which were exposed to fluxapyroxad (0.03 µM, 0.3 µM and 3 µM) from 3 h post fertilization (hpf) to 3 days post fertilization (dpf). Compared to the control groups, the hemoglobin was ectopic and decreased in response to fluxapyroxad treatment. The transcription levels of genes (hbbe1, hbbe2, and gata1a) involved in erythropoiesis were reduced after exposure to fluxapyroxad. In contrast, the distributions and expression of marker genes for myeloid lineage cells were unaffected by fluxapyroxad exposure. Our data suggested that fluxapyroxad might specifically affect erythropoiesis and hold great promise for the assessment of the toxicity of fluxapyroxad to aquatic organisms.


Database Development for Antibody Arrays.
Antibody arrays have been widely applied in both basic research and clinical studies. Data analysis, archiving, and sharing of resulting data are very important for exploring and expanding the power of antibody microarray studies. The protein microarray database (PMD) has provided standards tailored for the management of protein microarray data and constructed an automated pipeline for array data analysis. In this chapter, we will describe the framework design, platform construction, and analysis tool integration of the PMD.


Scleral buckling for primary rhegmatogenous retinal detachment using noncontact wide-angle viewing system with a cannula-based 25 G chandelier endoilluminator.
The aim of this study is to report the result of scleral buckling (SB) using a combination of a noncontact wide-angle viewing system and a cannula-based 25 G chandelier endoilluminator. Retrospective analyses of the medical records of 79 eyes of 79 patients with primary uncomplicated rhegmatogenous retinal detachments who had underwent SB using a combination of a noncontact wide-angle viewing system and a chandelier endoilluminator were performed. There were 50 men and 29 women. The mean ± standard deviation age was 43.7±16.0 years. Their preoperative best-corrected visual acuity (BCVA) was 0.31±0.65 logMAR units. The final BCVA was 0.10±0.31 logMAR units, which was significantly better than the preoperative BCVA (P<0.01). The initial and final anatomical success rates were 92.4% and 100%, respectively. Backward logistic multiple regression analysis revealed no relationship between explanatory variables and the primary anatomic success (P=0.104). SB using a combination of a noncontact wide-angle viewing system and a chandelier endoilluminator is a modified new technique and may be a valid option for the management of rhegmatogenous retinal detachments.


Blockage of P2X7 attenuates acute lung injury in mice by inhibiting NLRP3 inflammasome.
NLRP3 inflammasome is engaged in the inflammatory response during acute lung injury (ALI). Purinergic receptor P2X7 has been reported to be upstream of NLRP3 activation. However, the therapeutic implication of P2X7 in ALI remains to be explored. The present study used lipopolysaccharide (LPS)-induced mouse model to investigate the therapeutic potential of P2X7 blockage in ALI. Our results showed that P2X7/NLRP3 inflammasome pathway was significantly upregulated in the lungs of ALI mice as compared with control mice. P2X7 antagonist A438079 suppressed NLRP3/ASC/caspase 1 activation, production of IL-1β, IL-17A and IFN-γ and neutrophil infiltration but not the production of IL-10, resulting in a significant amelioration of lung injury. Moreover, blockage of P2X7 significantly inhibited NLRP3 inflammasome activation and IL-1β production in bone marrow derived macrophages. Similar results were obtained using another P2X7 inhibitor brilliant blue G (BBG) in vivo. Thus, pharmacological blockage of P2X7/NLRP3 pathway can be considered as a potential therapeutic strategy in patients with ALI.


Urgency and austerity as drivers of success.
This piece describes the approach by which even a small CADD (Computer-Aided Drug Design) group with limited resources and limited time can achieve substantial success given short budgets and the compressed, urgent environment of a biotech. Some comparisons are made with CADD operations in big pharma.


Social Integration may Moderate the Relationship between Neighborhood Vacancy and Mental Health Outcomes: Initial Evidence from Flint, Michigan.
Long-term residence in neighborhoods is thought to promote the development and maintenance of supportive relationships and trust. These strong social ties may, however, be limited in communities in post-industrial cities characterized by high levels of vacant properties. This study aimed to examine the relationship between neighborhood vacancy and mental health with adjustment for length of residence and possible moderation by social (dis)integration in a sample of Flint, MI, residents. We found that short-term (but not long-term) increases in neighborhood vacancy were associated with poorer mental health, after adjustment for individual covariates. When considering neighborhood vacancy, length of residence and individual covariates, however, the only significant association detected was between higher social disintegration and lower wellbeing. This effect was direct and not mediated by other factors. In this way, it appears that the social conditions of neighborhoods may be important, particularly in places that have experienced declines in the built environment. In addition, we identified evidence that social integration moderates the relationship between neighborhood vacancy and mental health outcomes. The level of neighborhood vacancies had a weaker relationship to wellbeing among those with higher levels of social ties. But none of the independent variables in our study were able to predict social integration, highlighting some potential areas for future research. From these findings, we posit that establishing strong social connections can buffer residents against negative mental health outcomes, and health promotion efforts could usefully assist in maintaining social ties among neighbors.


Short- and long-term changes of condylar position after bilateral sagittal split ramus osteotomy for mandibular advancement in combination with Le Fort I osteotomy evaluated by cone-beam computed tomography.
Bilateral sagittal split ramus osteotomy (BSSO) may change condylar position, which can be one of the factors contributing to skeletal relapse. This study evaluated short- and long-term changes in condylar position using cone-beam computed tomography (CBCT) and investigated changes in temporomandibular joint (TMJ) signs after BSSO for mandibular advancement in combination with Le Fort I osteotomy. Thirty-one patients were included, and CBCT data of 62 TMJs were collected before surgery (T0), immediately after surgery (T1), 3 months after surgery (T2), and at the last follow-up at 12.1 ± 3.0 months after surgery (T3). The relation of the condyle to the fossa was evaluated by the method of Pullinger and Hollender (Oral Surg Oral Med Oral Pathol 62:719, 1986). Clinical examination, with a special focus on signs of temporomandibular disorder (TMD), was documented at T0, T2, and T3. Repeated-measures analysis of variance (P = .05) and χ2 test (P = .05) were performed. Data of 27 patients were used for statistical analysis. Values from the formula of Pullinger and Hollender changed significantly with time, but there was no significant difference between the right and left condyles. Condyles moved inferoposteriorly immediately after surgery (T0 to T1) followed by anterosuperior movement 3 months after surgery (T1 to T2). The superimposed effect showed posterosuperior movement compared with the initial position before surgery (T0 to T2) and this position remained stable at 1-year follow-up (T2 to T3). A decrease of TMD signs over time, from 22.6% (T0) to 12.9% (T2) and 9.7% (T3), was observed, which showed no statistical significance. There were obvious changes in condylar position after BSSO in combination with Le Fort I osteotomy. Condyles tended to be located in a concentric position in relation to the glenoid fossa 3 months after surgery and remained stable during the 1-year follow-up. These changes did not cause an increase of TMD signs.


Metoclopramide in gastroesophageal reflux of infancy.
This study examined the effect of metoclopramide on lower esophageal sphincter (LES) pressure, and frequency and duration of reflux episodes in 28 children (mean age (+/- SD) 9 +/- 11 months) referred for evaluation of gastroesophageal reflux (GER). Esophageal manometry was performed before and after one intravenous dose of metoclopramide (0.125 mg/kg), and esophageal pH was monitored over a 24-hour baseline period, followed by oral metoclopramide therapy (0.125 mg/kg four times a day, for 24 hours.) During pH monitoring, patients received diet for age and were kept in the prone position with the head elevated 45 degrees while sleeping. Eight patients entered a 6-month double-blind, placebo-controlled trial of metoclopramide. Metoclopramide significantly (P = 0.04) increased end-expiratory LES pressure, from 14.9 +/- 7.5 mm Hg to 18.6 +/- 6.8 mm Hg. However, there was a significant (P less than 0.05) increase in the number of reflux episodes/24 hours, and no significant change in percentage of time pH was less than 4, number of episodes lasting greater than 5 minutes, or the longest episode of reflux between the 24-hour baseline and M periods. LES pressure did not correlate well with any of these measurements (r = 0.2). In the controlled trial, the three patients receiving metoclopramide, but none of those receiving placebo, were withdrawn by their parents because of exacerbation of GER symptoms and marked irritability (P = 0.01). In the placebo group, symptoms improved in four infants, but did not change in one. The use of metoclopramide in the treatment of GER of infancy needs to be reconsidered.


Mechanism of inhibition of proton: dipeptide co-transport during chronic enteritis in the mammalian small intestine.
Amino acids, a critical energy source for the intestinal epithelial cells, are more efficiently assimilated in the normal intestine via peptide co-transporters such as proton:dipeptide co-transport (such as PepT1). Active uptake of a non-hydrolyzable dipeptide (glycosarcosine) was used as a substrate and PepT1 was found to be present in normal villus, but not crypt cells. The mRNA for this transporter was also found in villus, but not crypt cells from the normal rabbit intestine. PepT1 was significantly reduced in villus cells also diminished in villus cell brush border membrane vesicles both from the chronically inflamed intestine. Kinetic studies demonstrated that the mechanism of inhibition of PepT1 during chronic enteritis was secondary to a decrease in the affinity of the co-transporter for the dipeptide without an alteration in the maximal rate of uptake (Vmax). Northern blot studies also demonstrated unaltered steady state mRNA levels of this transporter in the chronically inflamed intestine. Proton dipeptide transport is found in normal intestinal villus cells and is inhibited during chronic intestinal inflammation. The mechanism of inhibition is secondary to altered affinity of the co-transporter for the dipeptide.


Effect of an intracellular calcium antagonist (TMB-8) on carbamylcholine-induced amylase release from dispersed rat pancreatic acini.
During 10-min incubation with increasing concentrations of carbamylcholine (carbachol), amylase release from dispersed rat pancreatic acini increased, became maximal at 2 X 10(-6)M and then decreased. In the concentration range of 10(-7)M to 10(-4)M, 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) caused a dose-dependent inhibition of amylase release induced by a submaximal concentration of carbachol. No inhibitory effect was observed on basal and secretin-stimulated amylase release. TMB-8 showed a significantly greater ability of blocking the action of carbachol than verapamil and diltiazem. TMB-8 could reverse the submaximal stimulation of amylase release caused by supramaximal concentrations of carbachol to a maximal stimulation, while verapamil and diltiazem could not. These results confirm the hypothesis that mobilization of intracellular calcium is the primary step in the action of carbachol on pancreatin acinar cells and contributes to the submaximal secretory response of acinar cells induced by high concentrations of carbachol.


Lower prevalence than expected when screening 70-year-old men for abdominal aortic aneurysm.
Screening 65-year-old men for abdominal aortic aneurysms (AAA) is a cost-effective method to reduce the mortality from ruptured AAA. However, contemporary results show a lower than expected prevalence of AAA, thus questioning the benefit of screening. Since the prevalence increases with age, a possible way to enhance the benefit of screening might be to screen older men. Our aim was to determine the contemporary screening-detected prevalence among 70-year-old men. A total of 5,623 unscreened 70-year-old men were invited to ultrasound screening. Uni- and multivariable analyses were used to assess the risk factors for AAA. The attendance rate was 84.0%. The prevalence of previously unknown AAAs was 2.3%. When adding the 64 men with an already known AAA to the screening-detected ones, the total prevalence in the population was at least 3.0%, and the previously discovered AAAs constituted 37.4% of the total prevalence. "Ex smoker" and "Current smoker" were the most important risk factors. When screening 70-year-old men for AAA, the prevalence was less than half that expected, despite a high attendance rate. Smoking was the strongest risk factor. Almost 40% of the men with AAAs were already known from other means than screening.


Transfection of PDCD5 effect on the biological behavior of tumor cells and sensitized gastric cancer cells to cisplatin-induced apoptosis.
Programmed cell death 5 (PDCD5) expression is reduced in various human tumor cells, and the protein concentration and nuclear translocation of PDCD5 is also observed during tumor cell apoptosis. The purpose of this study was to investigate the differential expression of PDCD5 in six gastric cell lines, and to explore the changes of biological behavior mechanism underlying enhanced apoptosis-inducing effects of cisplatin by PDCD5 over-expression on gastric cancer BGC823 cells. RT-PCR and real-time PCR were used to determine PDCD5 expression. BGC823/PDCD5 cells were assessed the cellular proliferating ability by MTT assay, soft agar cloning experiments and tumorigenicity in nude mice experiments in vivo. The effects of cisplatin in combination with PDCD5 on the proliferation and apoptosis were measured by MTT, Annexin-V-FITC/PI dual labeling and cell cycle analysis, respectively. Immunofluorescence was used to detect co-localization of p53 and PDCD5 protein to explore the mechanism underlying the synergistic therapeutic effect of PDCD5 with cisplatin (5 μg/ml for 24 h). PDCD5 had the highest expression level in the GES1 cell among other cell lines. The growths of BGC823 cells transfected with PDCD5 for six (6th) or 17 (17th) days were both slower than that of BGC823 and BGC823/Neo (P < 0.01). The stable transfection of PDCD5 demonstrated G2/M cell cycle arrest, increased apoptosis and nuclear translocation of PDCD5 and p53 after cisplatin treatment. Stable transfection of the PDCD5 gene can inhibit the growth of the BGC823 cell line and notably improve apoptosis-inducing effects of cisplatin, indicating a novel strategy for better chemotherapeutic effects on gastric cancer.


Influenza virus interferon-inducing particle efficiency is reversed in avian and mammalian cells, and enhanced in cells co-infected with defective-interfering particles.
Naturally selected variants of influenza virus encoding truncated NS1 proteins were tested in chickens as candidate live-attenuated influenza vaccines. Their effectiveness correlated with the amount of interferon (IFN) induced in chicken cells. Effective variants induced large amounts of IFN and contained subpopulations with high ratios of defective-interfering particles:IFN-inducing particles (DIP:IFP). Ineffective variants induced less IFN and contained lower ratios of DIP:IFP. Unexpectedly, there was a reversal of phenotypes in mammalian cells. Variants that induced low amounts of IFN and had low DIP:IFP ratios in chicken cells were excellent IFN inducers with high DIP:IFP ratios in mammalian cells, and vice versa. The high DIP:IFP ratios and computer-simulated dynamics of infection suggested that DIP, as an individual particle, did not function as an IFP. The higher efficiency of IFPs in the presence of DIPs was attributed to reduced amounts of newly synthesized viral polymerase known to result from out-competition by defective-interfering RNAs, and the subsequent failure of that polymerase to turn-off cellular mRNA transcription-including IFN-mRNA.


Indirect effects of fish on macrophytes in Bays Mountain Lake: evidence for a littoral trophic cascade.
We began this experiment to test specific hypotheses regarding direct and indirect effects of fish predation on the littoral macroinvertebrate community of Bays Mountain Lake, Tennessee. We used 24 m2 enclosures in which we manipulated the presence and absence of large redear sunfish (Lepomis microlophus>150 mm SL), and small sunfish (L. macrochirus and L. microlophus <50 mm SL) over a 16-mo period. Here we report on effects of fish predation on gastropod grazers that appear to cascade to periphyton and macrophytes.Both large redear sunfish and small sunfish maintained low snail biomass, but snails in fish-free controls increased significantly during the first 2-mo of the experiment. By late summer of the first year of the experiment, the difference in biomass between enclosures with and without fish had increased dramatically (>10×). Midway through the second summer of the experiment, we noted apparent differences in the abundance of periphyton between enclosures containing fish and those that did not. We also noted differences in the macrophyte distribution among enclosures. To document these responses, we estimated periphyton cover, biovolume and cell size frequencies as well as macrophyte distributions among enclosures at the end of the experiment. When fish were absent, periphyton percent cover was significantly reduced compared to when fish were present. Periphyton cell-size distributions in enclosures without fish were skewed toward small cells (only 12% were greater than 200 m3), which is consistent with intense snail grazing. The macrophyte Najas flexilis had more than 60 x higher biomass in the fish-free enclosures than in enclosures containing fish; Potamogeton diversifolius was found only in fish-free enclosures. These results suggest a chain of strong interactions (i.e. from fish to snails to periphyton to macrophytes) that may be important in lake littoral systems. This contrasts sharply with earlier predictions based on cascading trophic interactions that propose that fish predation on snails would enhance macrophyte biomass.


Selective medium for the isolation of Mycoplasma bovis from nasal discharges of pneumonic calves.
Strains of bovine Mycoplasmatales exhibited two growth forms on a plate medium containing 0.1 per cent Tween 80. Colonies of Mycoplasma bovis could easily be differentiated from those of concomitant mycoplasmatales in that the former grew rapidly with film and spots, while colonies of M arginini and Acholeplasma species did not produce film and spots; the growth of M bovirhinis was completely inhibited.


The structure of the termini of the DNA of Epstein-Barr virus.
We have studied the DNA of Epstein-Barr virus (EBV) isolated from the B95-8 strain of that virus (Miller and Lipman, 1973). When EBV DNA is partially digested with lambda-exonuclease and allowed to reanneal, up to 50% of the full-length molecules circularize. The arrangements of nucleotide sequences containing the terminal repeats identified in this circularization experiment have been determined. Those fragments of viral DNA generated by digestion with restriction endonucleases which are terminal and contain the terminal repeats have been identified by their sensitivity to digestion of full-length DNA by lambda-exonuclease and by virtue of their being partially homologous to one another. The population of DNA molecules in the B95-8 strain of EBV was found to be nonuniform. The nonuniformity results from different molecules having different numbers of a 0.37 megadalton terminal repeat at each end. About 70% of molecules have four terminal repeats at one end, while four equal classes, each comprising approximately 25% of the population, have one, two, three or four repeats at the other end. The arrangements of nucleotide sequences identified as being terminal in virion DNA were studied in the intracellular circular viral DNA of cells transformed by a single particle on EBV. All fragments produced by digestion with endonucleases and scored as being terminal in virion DNA were absent from intracellular circular DNA. An additional fragment was identified in the digests of intracellular DNA of each transformed clone. The molecular weights of the new fragments equal the sum of the molecular weights of two terminal fragments which are joined upon intracellular circularization of viral DNA.


Comprehensive assessment of patients after coronary artery bypass grafting by 16-detector-row computed tomography.
Multidetector-row computed tomography (MDCT) is a versatile modality to evaluate stenoses in native coronary arteries and bypass grafts. Acquired MDCT data can additionally be used to assess left ventricular ejection fraction (LVEF). The purpose was to use MDCT for the assessment of bypass graft and coronary artery disease combined with evaluation of LVEF. Twenty-five patients underwent 16-detector-row CT examination and coronary angiography. Bypass grafts and nongrafted coronary artery segments at MDCT were evaluated on eligibility, patency, and > or = 50% stenosis. The MDCT data set was used to calculate LVEF and was divided into patients with no/subendocardial/transmural myocardial infarctions (MIs). Ninety vessels were evaluated: 14 arterial grafts/53 vein grafts/23 nongrafted vessels. Of 225 segments, 17 were ineligible for evaluation because of metal clips. With MDCT, patency in segments of arterial grafts/vein grafts/nongrafted vessels could be evaluated with high accuracy in 100%/100%/97% of segments. In arterial grafts, stenoses > or = 50% did not occur at angiography, which was for all eligible segments correctly diagnosed at MDCT. Stenosis > or = 50% could be correctly detected by MDCT with a sensitivity/specificity of 100%/94% for vein grafts and 100%/89% for nongrafted vessels. Negative predictive value was 100% for vein grafts and nongrafted vessels. In patients with transmural MI, MDCT revealed a significant lower LVEF as compared with patients without or with subendocardial MI (P < .05). Comprehensive assessment of bypass grafts, nongrafted vessels, and LVEF is feasible with MDCT. Owing to the high negative predictive value this noninvasive approach may be used as gatekeeper before coronary angiography.


Leptin and adiponectin as predictors of disease activity in rheumatoid arthritis.
To assess whether baseline levels of leptin and adiponectin predict disease activity or response to treatment in patients with RA at 6 months, 1 and 2 years of follow-up. A consecutive cohort of patients, classified according to the 2010 ACR/EULAR RA criteria, was evaluated at baseline, 6 months, 1 and 2 years. All were treated with steroids and/or DMARDs. None received biologics. Blood was taken at a baseline to determine plasma anti-CCP, leptin and adiponectin. The relationship between leptin, adiponectin, DAS28 and changes in DAS28 was assessed by multivariable linear and logistic regression from baseline to follow-up. 127 patients completed 6 months, 91 one year and 52 two years of follow-up. All were female, mean age 45 years (18-70), time since onset of disease 7.5 years (0-36). A U-shaped relationship between DAS28 and leptin baseline levels was seen. Adjusting for different factors, leptin levels at baseline predicted higher DAS28 at 6 months and, in patients who were not overweight or obese, predicted disease activity at 6 months, 1 and 2 years. In patients who were not overweight or obese, baseline leptin was able to predict response to treatment at 6 and 12 months. In the short term, baseline leptin levels predict disease activity in all RA patients and response to treatment in RA patients with normal weight.


Epidemiology of osteoarthritis.
Although OA is recognized as the most common joint disorder, its pathogenesis is unclear and little is known about its natural history and progression. Epidemiologic studies have identified age as the strongest and most consistent correlate of OA, with distinct patterns of distribution by sex, ethnicity, and geographic location. There is growing consensus that OA represents a heterogeneous set of diseases that are affected by the interaction of multiple risk factors, producing a common pathway of disease; and that it is important to study multiple risk factors in association with generalized OA and site-specific subsets of OA. Two basic types of generalized OA are recognized, although it is quite possible that there are additional types of generalized OA. Genetic susceptibility, which implies some systemic factor of cartilage vulnerability, is thought to be the major risk factor for generalized OA. Mechanical factors associated with wear and tear on the joint have been the most important factors found in association with site-specific OA, although it is possible that systemic factors are also involved. Most likely there are multiple factors, such as genetic susceptibility; anatomic, biomechanical, and biochemical changes associated with aging; and exposure to various types of joint trauma and injury that are implicated in the etiology of OA. There is little known about progression of OA and the extent of the outcomes involved with progression of OA. Crucial to future epidemiologic research is the identification of homogeneous subsets of OA that facilitate standardized case definition, and research designs that incorporate multiple joints in one study and investigate the independent and interactive effects of multiple hypothesized risk factors. Cohort studies and longitudinal follow-up of persons with OA are needed in order to have a better understanding of the natural history of OA and its related outcomes.


Real-time monitoring for sport and mental health prevention of college student based on wireless sensor network.
This article uses wireless sensor network technology to freely combine multiple sensor nodes to achieve, but the scale and capacity of WSN internal nodes are limited, so it is easier to encounter a series of network attacks and security threats. When setting the access protocol, the protocol needs to identify the precautions for malicious attacks against the network, and at the same time try to achieve a balance between network weights to improve the life cycle of the network. This paper presents a multi-station basis for a wireless sensor connection system. The design uses elliptic curve encryption technology to ensure the security of identification between the base station and the cluster head, and uses blockchain technology to ensure the security and efficiency of the ID card between the base station and the terminal. And design a real-time monitoring system through wireless sensor network to monitor the sport and mental health of students. We have analyzed the system demand information of college students' sport and mental health, and analyzed the problems that the system needs to solve in detail. Through in-depth analysis of the sport and mental health information system, using wireless sensor network technology, we conducts a thorough investigation of the needs of the student sport and mental health system. Then we conduct an in-depth analysis of the system structure, architecture design, business model, available system, database system, to make the system more acceptable to people.


RETRACTED: LncRNA GAS6-AS1 facilitates the progression of breast cancer by targeting the miR-324-3p/SETD1A axis to activate the PI3K/AKT pathway.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the current Editor in Chief, with the agreement of all authors. The article is being retracted due to inappropriate manipulation of the original data for presentation in Figures 2C, 5C and 6C. Upon further investigation and discussion with the authors, insufficient evidence was provided to support a reasonable explanation for these mistakes. In addition, the authors could not provide convincing original data supporting other figures of the manuscript, e.g. Figures 2G, 4 and 6A. Based on these findings, the Editor in Chief and the authors have decided to retract the study. The authors apologize for any inconvenience caused.


Role of bile acids and neutral sterols in familial cancer syndromes of the colon.
Cholesterol is quantitatively the most significant sterol in mammalian tissues. The major metabolic pathway of this sterol leads to the formation of bile acids. The structural similarities between carcinogenic aromatic hydrocarbons and bile acids aroused the suspicion that bile acids might play a role in carcinogenesis. In familial polyposis, a condition with a strong genetic predisposition to colonic cancer, a failure to degrade fecal cholesterol and bile acids to secondary products has been postulated as a marker of the phenotypic expression of this condition. In contrast, epidemiologic studies in populations at high risk for colonic cancer, and consuming diets rich in animal fat, protein, and refined carbohydrates, show a positive correlation with high fecal concentrations of bile acids and their metabolites. The suggestion that secondary bile acids might act in concert with colonic carcinogens in promoting neoplastic transformation is supported by observations from experimental studies. Among the secondary bile acids, lithocholic acid is unique in that it has been shown to be comutagenic, promote cell transformation, and induce DNA strand breakage, in vitro. It has also been shown to bind covalently to tissue proteins in human liver and in livers of carcinogen-treated rats.


Bilateral striatal necrosis, dystonia and multiple mitochondrial DNA deletions: case study and effect of deep brain stimulation.
Bilateral striatal necrosis (BSN) is relatively rare and has been related to a wide array of causes, including nuclear and mitochondrial DNA mutations. We report the clinical vignette of a patient with a 37 year-history of generalized dystonia secondary to BSN associated with multiple mitochondrial DNA deletions of undefined origin. Globus pallidus interna deep brain stimulation produced sustained benefit, with predominant improvements in disability.


Phentermine involvement in fatal drug overdoses in Tennessee, 2019-2022.
Phentermine, one of the most-commonly prescribed pharmaceuticals for weight-loss in the United States (US), has appeared on toxicology and listed as a cause of death in fatal drug overdoses in the state of Tennessee. This study aims to evaluate phentermine's involvement in fatal drug overdoses in the state of Tennessee. We used Tennessee State Unintentional Drug Overdose Reporting System (SUDORS) data and controlled substances monitoring program data (CSMD) to evaluate demographics, prescription history and co-occurring substances on toxicology in phentermine-positive cases compared with all other SUDORS cases from January 1, 2019 to June 30, 2022. A subset of these cases which listed phentermine as a cause of death was also assessed. We identified 51 phentermine-positive cases, with a subset of 20 that listed phentermine as a cause of death. When compared to all SUDORS cases, a higher proportion of cases that listed phentermine as a cause of death were White race, females, and aged 35-44. Additionally, in all phentermine-positive cases, 41% (21) of decedents had not had a phentermine prescription dating back to 2012 and 20% (Lee et al., 1998) did not have one within the last 30 days. While there was a slight decline each year in the number of phentermine-positive cases, the number of cases that listed phentermine as a cause of death remained relatively consistent, with 95% (19) of cases having different prescriptions and/or illicit drugs listed as a cause of death along with phentermine. Phentermine was listed as a cause of death in 20 fatal drug overdoses in TN. Our findings suggest there may be differences in the characteristics of these decedents when compared to all SUDORS decedents, including distribution of age, gender, and race. We also found a large presence of other prescription and illicit drugs in toxicology and cause of death along with phentermine, as well as evidence of use of the drug without a prescription. Given the lack of currently available data about non-prescribed phentermine use and its involvement in fatal drug overdoses elsewhere, a need exists to both expand surveillance capabilities and broaden research to better inform policies governing this drug in the US and internationally.


Validated detection of human anti-chimeric immune responses in serum of neuroblastoma patients treated with ch14.18/CHO.
Human/mouse chimeric monoclonal antibody (mAb) ch14.18/CHO is directed against disialoganglioside GD2. Activity and efficacy of this mAb are currently determined in ongoing clinical Phase II and -III studies in high-risk neuroblastoma (NB). Based on the chimeric nature of this mAb, some patients may develop a human anti-chimeric immune response (Mirick et al., 2004) which impacts on pharmacokinetics and may induce anti-anti-idiotype (Id) mAb with a potential survival benefit. Therefore, a validated method of quantitative detection of human anti-chimeric antibodies (HACA) in serum samples of NB patients treated with ch14.18/CHO is an important tool for monitoring of clinical trials. Here, we report a validated sandwich enzyme-linked immunosorbent assay (ELISA) according to the one arm binding principle using ch14.18/CHO as a capture mAb and biotinylated ch14.18/CHO mAb for detection. Ganglidiomab, a monoclonal anti-Id Ab to ch14.18/CHO (Lode et al., 2013), was used as a standard for assay validation and HACA quantification. Systematic evaluation of the established ELISA procedure revealed an optimal serum sample dilution factor of 1:160. Assay validation was accomplished with a set of tailored quality controls (QC) containing distinct concentrations of ganglidiomab (3 and 15μg/ml). The coefficients of variation (CV) for all within-assay and inter-assay measurements using QCs were under 20% and the limit of detection (LOD) was 1.1μg/ml. Three patients (P1, P2, P3) treated with a 10day continuous infusion of 100mg/m(2) of ch14.18/CHO were selected for analysis with this assay. Selection was based on ch14.18/CHO drug level on day 8 in cycle 2 of >10μg/ml (expected) (P1) and of <2μg/ml (unexpected) (P2 and P3). Both patients with unexpected low ch14.18/CHO levels revealed a strong signal in the HACA ELISA. Interestingly, ch14.18/CHO-mediated complement-dependent cytotoxicity (CDC) could not be detected in P2 in contrast to P3 suggesting anti-NB activity even in the presence of HACA. We showed that neither eight freeze-thaw cycles nor storage at room temperature for up to 168h affected HACA stability in serum. In summary, we describe a validated ELISA method suitable for the assessment of HACA in NB patients treated with ch14.18/CHO.


Bradykinin-pretreated Human cardiac-specific c-kit+ Cells Enhance Exosomal miR-3059-5p and Promote Angiogenesis Against Hindlimb Ischemia in mice.
Protection of cardiac function following myocardial infarction was largely enhanced by bradykinin-pretreated cardiac-specific c-kit+ (BK-c-kit+) cells, even without significant engraftment, indicating that paracrine actions of BK-c-kit+ cells play a pivotal role in angiogenesis. Nevertheless, the active components of the paracrine actions of BK-c-kit+ cells and the underlying mechanisms remain unknown. This study aimed to define the active components of exosomes from BK-c-kit+ cells and elucidate their underlying protective mechanisms. Matrigel tube formation assay, cell cycle, and mobility in human umbilical vein endothelial cells (HUVECs) and hindlimb ischemia (HLI) in mice were applied to determine the angiogenic effect of condition medium (CM) and exosomes. Proteome profiler, microRNA sponge, Due-luciferase assay, microRNA-sequencing, qRT-PCR, and Western blot were used to determine the underlying mechanism of the angiogenic effect of exosomes from BK-c-kit+. As a result, BK-c-kit+ CM and exosomes promoted tube formation in HUVECs and the repair of HLI in mice. Angiogenesis-related proteomic profiling and microRNA sequencing revealed highly enriched miR-3059-5p as a key angiogenic component of BK-c-kit+ exosomes. Meanwhile, loss- and gain-of-function experiments revealed that the promotion of angiogenesis by miR-3059-5p was mainly through suppression of TNFSF15-inhibited effects on vascular tube formation, cell proliferation and cell migration. Moreover, enhanced angiogenesis of miR-3059-5p-inhibited TNFSF15 has been associated with Akt/Erk1/2/Smad2/3-modulated signaling pathway. Our results demonstrated a novel finding that BK-c-kit+ cells enrich exosomal miR-3059-5p to suppress TNFSF15 and promote angiogenesis against hindlimb ischemia in mice.


Children's neural responses to a novel mathematics concept.
Functional MRI studies have suggested a 'frontoparietal shift' over the course of development, whereby children tend to engage prefrontal neural regions to a greater extent than adults when completing mathematics tasks. Although this literature hints that lateral prefrontal regions may be involved in acquiring mathematics knowledge, a key limitation of existing studies is that they have included mathematics content that children already are familiar with as opposed to examining the dynamic learning process. We aimed to address this gap by examining children's neural responses when exposed to a new, unfamiliar mathematics concept. Eighteen 8-11 year old children viewed blocked demonstrations of base-2/binary (unfamiliar) and base-10/decimal (familiar) number systems while undergoing functional MRI (fMRI). Children's behavioral understanding of binary numbers was measured between fMRI runs. Counter to hypotheses, there were no overall differences in prefrontal activity for binary relative to decimal blocks. However, children with higher levels of behavioral understanding of the novel, binary concept showed enhanced neural activity in the left rostral middle frontal gyrus specifically during binary concept exposure. They also showed enhanced connectivity between this region and pre-and post-central gyri and left parahippocampal regions. Individual differences in children's behavioral grasp of a new mathematics concept correlate with prefrontal activity and functional connectivity during exposure to the concept, suggesting that rostral prefrontal cortex may play a role in mathematics learning.


The uses and benefits of cluster analysis in pharmacy research.
Cluster analysis (CA) refers to a set of analytic procedures that reduce complex multivariate data into smaller subsets or groups. Compared with other data reduction methods, such as factor analysis, CA yields groupings that are based on the similarity of whole cases, as opposed to the individual variables that comprise those cases. CA represents a valuable analytic tool for the health sciences, and may be used to devise patient or consumer profiles, or in the development of classification systems or taxonomies. CA has become a more widely used analytic tool because before the advent of personal computers with high processing power, CA methods were too complex to be time efficient. Yet in the past few decades, interest in and the applied use of CA have advanced considerably. CA tools are now integrated into most popular statistical software packages and are therefore more accessible. The authors provide a discussion of CA that seeks to introduce the various methods, issues, and considerations to the researcher who is largely unfamiliar with CA. A conceptual understanding of CA is guided through breaking down CA into a series of steps and issues to consider including composition of the dataset, selection of variables, decisions about standardizing variables, selecting a measure of association, selecting a clustering method, determining the number of clusters, and interpretation. Because the range of CA methods is diverse, and because the steps within each method are so varied, an attempt to offer a complete "how-to" process in a single article is imprudent. Rather, the novice reader will be able to use this article as a starting point for conducting his or her own particular CA study.


Enhancement of the synthesis of specific cellular polypeptides in a temperature-sensitive Chinese hamster cell line (K12) defective for entry into S phase.
Temperature-sensitive Chinese hamster cells (K12) have been shown to be defective for the initiation of new rounds of DNA replication when incubated at the restrictive temperature (40.5 degrees). By temperature shift experiments with synchronous cultures, we have marked out the step at which the mutation is expressed as the four hours preceding the initiation of DNA synthesis. The block imposed by the mutation has been shown to be irreversible. In order to approach the biochemical characterization of the temperature-sensitive function in K12 cells, we have analyzed the cellular proteins synthesized under permissive (35 degrees) and restrictive temperatures. The synthesis of three polypeptides is markedly enhanced when K12 cells are incubated at 40.5 degrees. One of them (band B) has turned out to be a useful biochemical marker of the expression of K12 mutation since its synthesis is not affected in other ts-mutants or in hybrids in which K12 mutation is complemented. In addition, the alteration in band B synthesis is irreversible and occurs during the same stage of the cell cycle at which the mutated function is expressed.


Antigen-specific proliferative human T cell clones with specificity for diphtheria toxoid: genetic and molecular restriction by class II antigens.
Human T lymphocyte clones (TLC) specific for diphtheria toxoid (DT) were isolated from a DR6/7 individual by cloning in soft agar in vivo sensitized T lymphocytes. We report here the isolation and characterization of 3 of these clones by studying: (a) the kinetic of activation, (b) the surface phenotypes, (c) the fine specificity for one of the 2 DT chains and (d) the genetic restriction of the proliferative response by the haplotype DR7. Moreover, blocking studies of the proliferative response to DT by various immunochemically characterized anti-HLA-DR monoclonal antibodies indicate that, on the DR7 molecule, more than one Ia determinant may participate in the clonal DT proliferative response. By using human TLC of a defined specificity and well-characterized anti-DR monoclonal antibodies, such studies may help to define the functional repertoire of Ia molecules in man.


Streptococcus pneumoniae: the role of apoptosis in host defense and pathogenesis.
Programmed cell death or apoptosis is a recognised feature of infection with Streptococcus pneumoniae, and is observed during pneumococcal meningitis and pneumonia. The cholesterol-dependent cytolysin, pneumolysin, is a major trigger of apoptosis in the brain in association with pneumococcal production of hydrogen peroxide. Pneumococcal cell wall is also an important stimulus for apoptosis. Microbial factors and host factors combine in causing apoptosis in the brain, with hippocampal neurons being particularly susceptible. In pulmonary infection epithelial cell apoptosis contributes to tissue injury but macrophage apoptosis may benefit the host, aiding microbial killing and downregulating the inflammatory response. During sepsis lymphocyte apoptosis may be harmful to the host while dendritic cell apoptosis may limit the generation of an adaptive immune response during infection. Apoptosis induction may be harmful or potentially beneficial during pneumococcal infection and understanding its function in each setting is essential to allow specific therapeutic intervention.


Avoiding and managing complications in the periorbital area and midface.
The eyes play a central role in the perception of facial beauty. The goal of periorbital rejuvenation surgery is to restore youthful proportions and focus attention on the eyes. Blepharoplasty is the third most common cosmetic procedure performed today. Because of the attention placed on the periorbital region, preventing and managing complications is important. Obtaining a thorough preoperative history and physical examination can significantly reduce the incidence of many of the complications. This article focuses on the preoperative evaluation as it relates to preventable complications, followed by common intraoperative and postoperative complications and their management.


N6-methyladenosine reader YTHDF3 regulates melanoma metastasis via its 'executor'LOXL3.
A number of studies have demonstrated that N6-methyladenosine (m6A) plays a vital role in the pathological process of various tumours. Recently, it was found that m6A writers or erasers affect the tumourigenesis of melanoma. However, the relationship between m6A readers such as YTH domain family (YTHDF) proteins and melanoma was still elusive. RT-qPCR, Western blot and immunohistochemistry were conducted to measure the expression level of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and lysyl oxidase-like 3 (LOXL3) in melanoma tissues and cells. The effects of YTHDF3 and LOXL3 on melanoma were verified in vitro and in vivo. Multi-omics analysis including RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses was performed to identify the target. The interaction between YTHDF3 and LOXL3 was verified by RT-PCR, Western blot, MeRIP-qPCR, RIP-qPCR and CRISPR-Cas13b-based epitranscriptome engineering. In this study, we found that m6A reader YTHDF3 could affect the metastasis of melanoma both in vitro and in vivo. The downstream targets of YTHDF3, such as LOXL3, phosphodiesterase 3A (PDE3A) and chromodomain helicase DNA-binding protein 7 (CHD7) were identified by means of RNA-seq, MeRIP-seq, RIP-seq and mass spectrometry analyses. Besides, RT-qPCR, Western blot, RIP-qPCR and MeRIP-qPCR were performed for subsequent validation. Among various targets of YTHDF3, LOXL3 was found to be the optimal target of YTHDF3. With the application of CRISPR-Cas13b-based epitranscriptome engineering, we further confirmed that the transcript of LOXL3 was captured and regulated by YTHDF3 via m6A binding sites. YTHDF3 augmented the protein expression of LOXL3 without affecting its mRNA level via the enrichment of eukaryotic translation initiation factor 3 subunit A (eIF3A) on the transcript of LOXL3. LOXL3 downregulation inhibited the metastatic ability of melanoma cells, and overexpression of LOXL3 ameliorated the inhibition of melanoma metastasis caused by YTHDF3 downregulation. The YTHDF3-LOXL3 axis could serve as a promising target to be interfered with to inhibit the metastasis of melanoma.


Reproduction and clonal growth in Potentilla anserina L. (Rosaceae): the relation between growth form and dry weight allocation.
Allocation to clonal growth and reproduction were investigated in the stoloniferous plant Potentilla anserina L. The aim was to reveal how the dry weight allocation pattern is related to an aspect of grwoth form: apical meristem utilization. A density mediated change in size did not affect the relation between reproduction and clonal growth. This pattern resulted from a shift in meristem utilization. The possibility of growth form constraints on dry weight allocation is discussed.


[Effects of microwave power on temperature change in dental pulpal chamber in vitro].
To explore the effects of microwave powers on temperature changes of dental pulpal chamber in vitro. 96 isolated teeth were prepared in three degrees of dental occlusal wear according to Smith BG's report. Temperature change values in dental pulpal chamber were recorded by thermometer (DM 6801A) while the different affect time and microwave powers acted directly and with 75% sodium fluoride glycerine paste on face of isolated teeth separately in room temperature. The degree of temperature in dental pulpal chamber was going up follow the raising microwave power and prolonging time. The temperature in dental pulpal chamber with microwave acting sodium fluoride on dental occlusal was higher than acting directly dental occlusal. The microwave power, time and degree of dental occlusal wear are very important factors on temperature change in dental pulpal chamber in our study.


Evaluation of partner collaboration to improve community-based mental health services for low-income minority children and their families.
This paper describes a mixed methods evaluation of partner agency collaboration within a system of care implemented from 2010 to 2012 in a historically underserved minority community in Houston, Texas. The first section describes the project and the framework for evaluating partner agency collaboration. The second section describes the evaluation methods and presents the baseline and follow-up results of the evaluation. The third section includes a discussion of the evaluation findings, the conclusion, and the lessons learned.


Comparison of Graft Survival Between Full-Thickness and Lamellar Pig-to-Monkey Corneal Xenotransplantation from the Same Genetically Engineered Pig Model with Minimal Immunosuppression.
The graft survival rate of full-thickness corneal xenotransplantation (XTP) with minimal immunosuppression in genetically engineered pigs is unknown, whereas lamellar corneal XTP shows satisfactory results. We compared graft survival between full-thickness and lamellar transplantations in the same genetically engineered pig. Six pig-to-monkey corneal transplantations were performed on 3 transgenic pigs. Two corneas harvested from 1 pig were transplanted into 2 monkeys using full-thickness and lamellar corneal xenotransplantation. The transgenic donor pigs used were α1,3-galactosyltransferase gene-knockout + membrane cofactor protein (GTKO+CD46) in one recipient and GTKO+CD46+ thrombomodulin (TBM) in the other. The graft survival time for GTKO+CD46 XTP was 28 days. With the addition of TBM, the survival differences between lamellar and full-thickness XTP were 98 days versus 14 days and >463 days (ongoing) versus 21 days, respectively. An excessive number of inflammatory cells was observed in failed grafts, but none were in the recipient's stromal bed. Unlike full-thickness corneal XTP, lamellar xenocorneal transplantation does not exhibit surgical complications, such as retrocorneal membrane or anterior synechia. The graft survival of lamellar XTP in this study was not as good as in our previous experiments, although the survival period was superior to that of full-thickness XTP. The difference in graft survival based on transgenic type is not definitive. Further studies using transgenic pigs and minimal immunosuppression need to focus on improving graft survival of lamellar XTP and using a larger sample size to determine the potential of full-thickness corneal XTP.


Cytoplasmic location of linoleoyl-CoA desaturase in microsomal membranes of rat liver.
The intramembrane localization of linoleoyl-CoA desaturase in rat liver microsomes was examined by various methods, such as digestion by proteases, effect of detergents, and inhibition by the antibodies against purified terminal desaturase. Exposure of the desaturase on the surface of microsomal vesicles was suggested by the fact that the enzyme activity in the intact microsomes was susceptible to tryptic digestion, and considerably inhibited by anti-desaturase antibodies. When microsomes were previously treated with trypsin, the enzyme became more susceptible to the antibodies. Furthermore, it was demonstrated that the protein fragments cleaved from microsomal membranes by tryptic digestion formed a single precipitin line with the antibodies by the double-immunodiffusion test. These findings suggest the presence of linoleoyl-CoA desaturase on the cytoplasmic surface in the endoplasmic reticulum, since tryptic digestion liberates only the protein components situated on the surface area of membranes. In addition, desaturase activity in the intact microsomes was not stimulated by addition of the detergent, indicating the further outside location of the active site of the enzyme in microsomal vesicles. The pretreatment of microsomes with a low concentration (0.05%) of sodium deoxycholate, which destroys the permeability barrier for macromolecules without membrane disassembly, did not increase the susceptibility to tryptic digestion and the antibodies. These results show that linoleoyl-CoA desaturase is not present in a latent state in the membrane.


Effect of a Nursing Comprehensive Skill Training Course (NCST-C) on Nursing Students' Metacognitive Awareness: A Quasi-experimental Study.
This study explored the effect of a nursing comprehensive skill training course (NCST-C) on the metacognitive awareness of nursing students to provide a scientific foundation for improving metacognitive awareness. This study used a quasi-experimental two-group matched pretest, post-test, and follow-up test. Ninety-six junior nursing students were recruited using convenience sampling and assigned to two groups by drawing lots with odd and even numbers in a nursing school at Huzhou University. The control group received a traditional skill-training course. The intervention group received NCST-C. Nursing students' metacognitive awareness inventory (MAI) was evaluated at the baseline, 16-week, and 20-week follow-up points. A repeated-measures analysis of variance and a simple effect test was used to compare each outcome measure of the two groups three times. The NCST-C resulted in greater benefits for nursing students' metacognitive awareness as well as various dimensions (knowledge of cognition and regulation of cognition) in the intervention group. Combined with a simple effects test, the MAI and dimension scores of those in the intervention group significantly improved at 16 weeks after the baseline (F = 9.78-44.03; all ps < .01). The sustainable effect of NCST-C lasted 1 month after the intervention (F = 14.24-62.36; ps < .01), reaching statistical significance (p < .05). The NCST-C effectively developed metacognitive awareness among nursing students. Its design provides a new type of experimental course for improving metacognitive awareness. chictr.org.cn: ChiCTR2200057910. First registration date: 1/11/2020.


Transient washout of hepatic hemangiomas: Potential pitfall mimicking malignancy.
Hemangiomas are the most common tumor of the liver and distinguishing them from malignancy is important. This is a report of 3 hemangiomas in 2 patients that exhibit transient washout of gadoxetate disodium (Eovist), relative to blood pool and liver parenchyma, a characteristic that is used to diagnose hepatocellular carcinoma in at-risk patients. It is important to recognize that high-flow hemangiomas can exhibit transient washout when using a small volume of injected contrast agent. This finding is unlikely to be present on CT examinations because of the larger volume of contrast administered.


Vale Professor Patrick Wall.
Professor Patrick Wall changed the way we think about pain. Until the middle of the 20th Century, pain was considered primarily to be a symptom of disease or injury. Pain was classically viewed in terms of a single mechanism consisting of a modality-specific, hard-wired system of nerve fibres running between the periphery and a specific pain centre in the brain. The implication of this view was that pain could only result from clear tissue pathology, with the result that physiotherapy treatment was often directed at the peripheral source of the pain. However, this does not fit with clinical observation, in that there is little correlation between the amount of tissue damage suffered by patients and the degree of pain that they feel.


Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach.
We have developed a computer assisted learning package for teaching clinical medical students about familial breast cancer. It explains the principles of genetic predisposition to breast cancer, the association with other cancers, the principles of family history taking and confirmation, risk assessment and possible interventions. Clinical medical students were randomised to either conventional teaching or CAL, 48 students attended the evaluation session. Students randomised to conventional teaching received a 20 min mini-lecture, those randomised to CAL completed the package with technical, but not academic support available. At the end of the intervention both groups of students completed a short written assessment of acceptability and knowledge and understanding of breast cancer genetics. There was no significant difference between the CAL and mini-lecture groups in terms of marks or acceptability. Thus CAL appears to be an acceptable and effective method of teaching clinical medical students about familial breast cancer. Although time consuming to develop, CAL can be used in a variety of settings to increase curriculum flexibility. Methods of motivating students to complete the CAL, and of providing educational support are being explored.


Damage to and recovery of coastlines polluted with C-heavy oil spilled from the Nakhodka.
The damage to and recovery of the Japanese coastline from Suzu, Ishikawa Prefecture to Mikuni, Fukui Prefecture was investigated visually over three years after a C-heavy oil spill from the Russian tanker "Nakhodka" in the Japan Sea on January 2, 1997. The beached C-heavy oil tended to remain for a long time on coasts of bedrock and boulder/cobble/pebble but it was removed rapidly from coasts of gravel/sand and man-made structures such as concrete tetrapods. On the coasts of the latter type, wave energy appeared to be the main force removing the oil. One year after the spill, C-heavy oil tended to remain strongly on the sheltered coasts of bedrock and boulder/cobble/pebble. Even on coasts of this type, the contamination was remarkably absent by 2 years after the spill. The concentration levels of polycyclic aromatic hydrocarbons (PAHs) in oil lumps, sand and seawater were monitored during 3 years following the spill. The concentrations of PAHs having 2 or 3 rings decreased more quickly than did those of PAHs having 4 or more rings, suggesting that volatilization was the main cause of the decrease. On the other hand, the concentrations of PAHs having 4 to 6 rings did not start to decrease until 7 months after the spill. The main cause of the decrease seemed to be photolysis. The concentration of BaP in seawater off the polluted coasts was high 1 month after the spill and then decreased. Three years after the spill, the level fell to the sub ng/L level, which was as low as the level in seawater along unpolluted clean coasts in Japan. The concentration of BaP in greenling was higher than the normal level only during the first two months after the spill. These results suggest that the coastlines in Ishikawa and Fukui Prefectures that were polluted with C-heavy oil recovered in 3 years.


Inhibition of pyrimidine biosynthesis de novo in Plasmodium falciparum by 2-(4-t-butylcyclohexyl)-3-hydroxy-1,4-naphthoquinone in vitro.
The effects of the hydroxynaphthoquinone BW58C on some metabolite levels and the flux of H14CO3 through the de novo pyrimidine biosynthetic pathway of intact Plasmodium falciparum have been studied in vitro using HPLC techniques. 800 nM BW58C appeared to have no significant effect on the energy status of isolated P. falciparum, but at 0.1 nM it caused a dramatic decrease in the concentrations of pyrimidine nucleotides, specifically UTP, during 256 min of incubation. Although about one hour was required to achieve a significant decrease in pyrimidine nucleotide concentrations, a much more rapid inhibition of the flux of H14CO3 through the de novo pathway was found upon addition of 0.1 nM BW58C. This inhibition caused about a 10 fold increase in the radioactivity of carbamoyl-aspartate over a 64 min period, and an overall increase in the concentration of this metabolite of about 3 fold during 256 min of incubation. These effects of BW58C against P. falciparum in vitro are discussed in terms of inhibition of de novo pyrimidine biosynthesis at the site of dihydroorotate dehydrogenase.


Conjugal amyotrophic lateral sclerosis: a report on a couple from Sardinia, Italy.
A conjugal case of amyotrophic lateral sclerosis (ALS) observed in Sardinia, Italy is reported. This is believed to be the ninth such observation described in the literature. The couple had lived together for 38 years in a house adjacent to the distillery they owned. No exogenous factors were revealed which could explain the genesis of the disease in either patients. Particularly, exposure to alcohol does not appear to have been involved in causing ALS. On the basis of statistical and epidemiological evaluations, the most likely explanation is that this association was purely coincidental.


The price is right: Routine fluorescent cholangiography during laparoscopic cholecystectomy.
Early experience with indocyanine green-based fluorescent cholangiography during laparoscopic cholecystectomy suggests the potential to improve outcomes. However, the cost-effectiveness of routine use has not been studied. Our objective was to evaluate the cost-effectiveness of fluorescent cholangiography versus standard bright light laparoscopic cholecystectomy for noncancerous gallbladder disease. A Markov model decision analysis was performed comparing fluorescent cholangiography versus standard bright light laparoscopic cholecystectomy alone. Probabilities of outcomes, survival, toxicities, quality-adjusted life-years, and associated costs were determined from literature review and pooled analysis of currently available studies on fluorescent cholangiography (n = 37). Uncertainty in the model parameters was evaluated with 1-way and probabilistic sensitivity analyses, varying parameters up to 40% of their means. Cost-effectiveness was measured with an incremental cost-effectiveness ratio expressed as the dollar amount per quality-adjusted life-year. The model predicted that fluorescent cholangiography reduces lifetime costs by $1,235 per patient and improves effectiveness by 0.09 quality-adjusted life-years compared to standard bright light laparoscopic cholecystectomy. Reduced costs were due to a decreased operative duration (21.20 minutes, P < .0001) and rate of conversion to open (1.62% vs 6.70%, P < .0001) associated with fluorescent cholangiography. The model was not influenced by the rate of bile duct injury. Probabilistic sensitivity analysis found that fluorescent cholangiography was both more effective and less costly in 98.83% of model iterations at a willingness-to-pay threshold of $100,000/quality-adjusted life year. The current evidence favors routine use of fluorescent cholangiography during laparoscopic cholecystectomy as a cost-effective surgical strategy. Our model predicts that fluorescent cholangiography reduces costs while improving health outcomes, suggesting fluorescence imaging may be considered standard surgical management for noncancerous gallbladder disease. Further study with prospective trials should be considered to verify findings of this predictive model.


Cardiac function in adolescents and young adults with 22q11.2 deletion syndrome without congenital heart disease.
Diagnosis and treatment of 22q11.2 deletion syndrome (22q11.2DS) have led to improved life expectancy and achievement of adulthood. Limited data on long-term outcomes reported an increased risk of premature death for cardiovascular causes, even without congenital heart disease (CHD). The aim of this study was to assess the cardiac function in adolescents and young adults with 22q11.2DS without CHDs. A total of 32 patients (20M, 12F; mean age 26.00 ± 8.08 years) and a healthy control group underwent transthoracic echocardiography, including Tissue Doppler Imaging (TDI) and 2-dimensional Speckle Tracking Echocardiography (2D-STE). Compared to controls, 22q11.2DS patients showed a significant increase of the left ventricle (LV) diastolic and systolic diameters (p = 0.029 and p = 0.035 respectively), interventricular septum thickness (p = 0.005), LV mass index (p < 0.001) and aortic root size (p < 0.001). 2D-STE analysis revealed a significant reduction of LV global longitudinal strain (p < 0.001) in 22q11.2DS than controls. Moreover, several LV diastolic parameters were significantly different between groups. Our results suggest that an echocardiographic follow-up in 22q11.2DS patients without CHDs can help to identify subclinical impairment of the LV and evaluate a potential progression of aortic root dilation over time, improving outcomes, reducing long-term complications and allowing for a better prognosis.


Evaluation of the Inhibitory Activities of COVID-19 of Melaleuca cajuputi Oil Using Docking Simulation.
GC-MS was applied to identify 24 main substances in Melaleuca cajuputi essential oil (TA) extracted from fresh cajeput leaves through steam distilling. The inhibitory capability of active compounds in the TA from Thua Thien Hue, Vietnam over the Angiotensin-Converting Enzyme 2 (ACE2) protein in human body - the host receptor for SARS-CoV-2 and the main protease (PDB6LU7) of the SARS-CoV-2 using docking simulation has been studied herein. The results indicate that the ACE2 and PDB6LU7 proteins were strongly inhibited by 10 out of 24 compounds accounting for 70.9% in the TA. The most powerful anticoronavirus activity is expressed in the order: Terpineol (TA2) ≈ Guaiol (TA5) ≈ Linalool (TA19) > Cineol (TA1) > β-Selinenol (TA3) > α-Eudesmol (TA4) > γ-Eudesmol (TA7). Interestingly, the synergistic interactions of these 10 substances of the TA exhibit excellent inhibition into the ACE2 and PDB6LU7 proteins. The docking results orient that the natural Melaleuca cajuputi essential oil is considered as a valuable resource for preventing SARS-CoV-2 invasion into human body.


Patient and clinic factors predictive of missed visits and inactive status in a multicenter clinical trial. The Macular Photocoagulation Study Group.
Obtaining complete patient follow-up in clinical trials is important for the analysis of treatment results and for good patient care. Incomplete data can introduce bias into study results and can alter conclusions concerning treatment efficacy. The purpose of this study was to explore in a case-control design patient and clinic factors that may be associated with missed visits or inactive status within three clinical trials conducted as part of the Macular Photocoagulation Study. All inactive patients, all patients with any missed visits, and a random sample of patients with no missed visits were selected for interview. A total of 175 patients (60% of 292 selected) participated in the study. Two factors were found to be significantly associated (P less than .05) both with inactive status and with having any missed visits: health problems and travel costs. Several patient and clinic factors were found to be associated only with inactive status. These included change in marital status since joining the study, retirement since study entry, unsatisfactory interactions with the study physician or clinic coordinator, too little time spent with the study physician, and patient's belief that participants should be paid to participate in clinical trials. Distance from the clinic greater than 100 miles, in addition to health problems any time during follow-up and problems with travel costs, was found to be associated only with having any missed visits. This study emphasizes the importance of maintaining good patient-staff interactions and sensitivity to the events in a patient's life in order to obtain complete patient follow-up.


Effectiveness of Indonesian house dust mite allergenic extract in triggering allergic rhinitis sensitivity in a mouse model: A preliminary study.
Perennial allergic rhinitis (AR) is a chronic upper respiratory disease, with inflammation mediated by immunoglobulin E in the nasal mucosa caused by house dust mites. Recently, allergen immunotherapy showed promising allergic healing in patients with a definite history of sensitization. Based on this finding, a product was developed using Indonesian house dust mite (IHDM). This study aimed to optimize the allergenic rhinitis mouse model that was generated using IHDM to test the in vivo sensitivity and safety of this product. Seven groups of mice were used for effectiveness testing - normal, negative control with IHDM challenge, positive control with 0.1% histamine challenge, and AR group by both IHDM-induced sensitization at 12.5, 50, 250, or 500 μg and IHDM challenge. Mice were sensitized by intraperitoneal administration of IHDM once a week for 3 consecutive weeks. Thereafter, the challenge was given intranasally 5 times on alternate days. The number of nose rubbing and sneezing was noted. Eosinophil infiltration was assessed histologically using hematoxylin and eosin staining. The expression of interleukin-5 (IL-5) mRNA in the nasal mucosa was determined using semi-quantitative reverse transcription-polymerase chain reaction. The induction of AR with IHDM significantly increased the number of nose rubbing and sneezing in the mouse model. Eosinophil infiltration was observed in the nasal mucosa; however, no significant change occurred in the expression of IL-5 mRNA. Overall, these data indicate that IHDM allergenic extract could be an effective sensitizing agent in a mouse model of AR. Although the use of IHDM is a limitation of this study because other sources of house dust mites might have different effects, this study provides a proper model for immunotherapy effectivity testing for in vivo pre-clinical studies.


5-Fluorouracil/folinic acid/cisplatin-combination and simultaneous accelerated split-course radiotherapy in advanced head and neck cancer.
In advanced inoperable head and neck cancer radiotherapy alone is unsatisfying. Better results can be obtained by simultaneous 5-Fluorouracil/Cisplatin-chemotherapy and irradiation. The cytotoxicity of 5-Fluorouracil can be enhanced synergistically by adding Folinic Acid in excess. In a clinical phase II trial 62 previously untreated patients suffering from unresectable AJCC-stage III (4 pts.) and IV (58 pts.) squamous cell carcinoma of the head and neck were treated with a simultaneous chemoradiotherapy consisting of high-dose Folinic Acid in addition to a 5-Fluorouracil/Cisplatin combination and of accelerated split-course radiotherapy. As results, three pts. died from tumor arrosion bleeding during the treatment. Median follow up time of the surviving pts. is 27 + months (range 18-44 months). 48/62 pts. (77%) achieved complete remission, 11/62 pts. (18%) partial remission. Presently, 32 pts. (52%) are without evidence of disease. Actuarial three years overall survival rate (Kaplan-Meier method) out of 62 pts. in 53%. Actuarial disease free survival and local tumor control rates at three years are 58% and 72%. Mucositis was severe but tolerable, bone marrow depression was moderate to marked. In conclusion, this combined simultaneous modality approach is highly effective in locally advanced head and neck cancer. It seems to provide superior survival and local control rates as compared to conventional radiotherapy or sequential chemo-radiotherapy or as compared to simultaneous 5-Fluorouracil/Cisplatin and non-fractionated radiotherapy. A comparative phase III study is required.


Design of a Complex fractional Order PID controller for a First Order Plus Time Delay system.
Complex fractional Order PID (COPID) controller is an extension to the Real fractional Order PID (ROPID) controller by extending the orders of differentiation and integration to include complex numbers, i.e., two extra parameters (the imaginary parts of the orders of the differentiator and the integrator) are introduced into the formula of the controller. The purpose is to overcome the limitation stemmed from restricting the parameters of the ROPID controller to belong to certain intervals, where this limitation results in a control system that does not satisfy the required design specification accurately. In this paper, analysis and design of COPID controller is presented, and for comparison purposes, both ROPID and COPID controllers are designed for a low pressure flowing water circuit, which is a First Order Plus Time Delay (FOPTD) system. The design specifications are given in frequency domain, which are gain crossover frequency, phase margin, and robustness against gain variation. The design specifications are taken as two cases, simple an rigorous, where the latter is considered to demonstrate the superiority of the COPID controller over the ROPID controller to achieve hard specifications. Although the design of the COPID controller is more complex than that of the ROPID controller, the first achieves the required design specification more accurately.


Development of amphotericin B-loaded propionate Sterculia striata polysaccharide nanocarrier.
This work was aimed at the production and characterization of a new nanocarrier based on a Sterculia striata polysaccharide (SSP) modified via acylation reaction with propionic anhydride. Nanocapsules of propionated SSP (PSSP) were produced via spontaneous nanoemulsification process and tested as a potential amphotericin B (AMB) nanocarrier. Stable nanoparticles with a very low polydispersity index (0.08-0.29) and high zeta potential (ζ -42.7 to -53.8 mV) were obtained. Particle size was dependent on the degree of substitution and ranged from 205 to 286 nm. A nanocapsule with a degree of substitution (DS) of 2.53 (NCP 2.53) was selected for encapsulation, biocompatibility, and antifungal evaluation against Candida albicans strains. A maximum of 98.3% AMB encapsulation was achieved. Encapsulated AMB was in its monomeric form and showed good biocompatibility and antifungal activity against four C. albicans strains. Data indicate that PSSP has potential as a nanocarrier system for AMB.


Retrospective evaluation of an iodophor-incorporated antimicrobial plastic adhesive wound drape.
The incidence of postoperative wound infection following the use of an iodophor-incorporated adhesive wound drape with a preliminary one-minute alcohol cleanse was observed in 649 total arthroplasties. The patients were followed for a minimum of one year to detect signs of infection. An infection rate of 0.46% was comparable to the incidence previously observed for conventional methods using an iodine spray as a skin preparation.


Sex ratio adjustment in Asobara persimilis (Hymenoptera: braconidae), a parasitoid of Drosophila.
Sex ratios of offspring in forty-one broods of Asobara persimilis (an hymenopteran parasitoid of Drosophila) were analysed. A single female wasp was introduced per tube of Drosophila larvae so that local mate competition would be expected to occur amongst their offspring. The parental population had a sex ratio of 1:1 (87F:102M), the offspring sex ratio was 787F:296M (2.66:1) highly female biased and not significantly different from 3:1 (P>0.05). The sex ratio was approximately constant regardless of the total brood size which ranged from 5 to 100 (mean 26.2). Females were therefore able to adjust their offspring sex ratios in the predicted direction and the number of males in each brood was determined binomially.


Non-radiation endoscopic removal of common bile duct stone assisted with abdominal ultrasonography in a pregnant patient.
A common bile duct stone was detected in a pregnant patient who was in her second trimester. Avoiding the use of fluoroscopy, abdominal ultrasonography-assisted endoscopic removal of the stone was successful.


Attenuated influenza produced by experimental intranasal inoculation.
To assess the relative effect of natural versus experimental influenza illness on pulmonary function, we compared 43 normal adults with documented nonpneumonic influenza A infection during three outbreaks, 1974 (A/Port Chalmers/74), 1975 (A/Port Chalmers/74), and 1976 (A/Victoria/75) to 24 normal volunteers following nasal inoculation with wild-type influenza A/England/42/72, A/Scotland/74 or A/Victoria/75. In naturally acquired illness, abnormalities in small airway functiion and transiently increase airway reactivity were observed. In contrast, no such dysfunction was observed in experimentally induced illness. This group manifested milder illness and significantly shorter duration of cough.


Widespread Protection of RNA Cleavage Sites by a Riboswitch Aptamer that Folds as a Compact Obstacle to Scanning by RNase E.
Riboswitches are thought generally to function by modulating transcription elongation or translation initiation. In rare instances, ligand binding to a riboswitch has been found to alter the rate of RNA degradation by directly stimulating or inhibiting nearby cleavage. Here, we show that guanidine-induced pseudoknot formation by the aptamer domain of a guanidine III riboswitch from Legionella pneumophila has a different effect, stabilizing mRNA by protecting distal cleavage sites en masse from ribonuclease attack. It does so by creating a coaxially base-paired obstacle that impedes scanning from a monophosphorylated 5' end to those sites by the regulatory endonuclease RNase E. Ligand binding by other riboswitch aptamers peripheral to the path traveled by RNase E does not inhibit distal cleavage. These findings reveal that a riboswitch aptamer can function independently of any overlapping expression platform to regulate gene expression by acting directly to prolong mRNA longevity in response to ligand binding.


Vasodilator response to histamine: dependence upon the site of administration.
Histamine causes vasodilation in part by interacting with histamine H2 receptors. The present study was undertaken to evaluate the difference in vasodilator sensitivity of H2 receptors on the inside compared to the outside of the vessel. In order to induce tone, norepinephrine was administered to an in vitro preparation of rabbit ear artery treated with mepyramine to block H1 receptors. Histamine was then either selectively perfused through the artery or added to the outside of the vessel via the organ bath. The outside of the artery was found to be twice as sensitive to the vasodilator effect of histamine as the inside. These data provide the first evidence for greater extraluminal sensitivity of vascular smooth muscle and suggest that the response to histamine will depend in part on the route the amine takes to reach receptors, e.g., from blood-borne sources or from extraluminal stores.


Keratoacanthoma.
The keratoacanthoma is a common cutaneous neoplasm that most often occurs on sun-exposed sites in light-skinned persons of middle age or older. It is considered the prototype of cutaneous pseudo-malignancies because it is a rapidly growing tumor with a histologic pattern resembling squamous cell carcinoma. It may be best viewed as an aborted malignancy that only rarely progresses into an invasive squamous cell carcinoma. It is most likely derived from hair follicle cells. The common type of keratoacanthoma and its many variants are discussed with emphasis on clinical and histologic features, biologic behavior, and response to therapy.


Synthesis of and pharmacological studies on the antidepressant and anticonvulsant activities of some 1,3,5-trisubstituted pyrazolines.
Eighteen 1-phenyl-, 1-thiocarbamoyl- and 1-N-substitutedthiocarbamoyl-3-phenyl-5-heteroaryl-2-pyrazoline derivatives were synthesized and tested for their antidepressant and anticonvulsant activities. Their chemical structures were proved by spectral and microanalysis. The antidepressant activities of the compounds were investigated by the "forced swimming test". Results showed that compounds II-a, b, c, III-1b, 1c, 4a showed activities equivalent to or higher than pargyline hydrochloride (CAS 306-07-0) and tranylcypromine sulfate (CAS 13492-01-8) that were used as reference antidepressant drugs. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES), subcutaneous metrazol (ScMet.) and rotarod toxicity tests in mice according to the phase I tests of the Antiepileptic Drug Development programme. Compounds I-a, II-a, b, c, III-1b, 2a, 2c were found protective against MES and III-1b, 1c, 2a, 2c were found protective against ScMet.