Pancreatic hypertrophy with acinar cell nodules after longterm fundectomy in the rat.
The effect of gastric fundectomy with hypergastrinaemia on the pancreas in rats was studied for 14 months. Rats with hypercholecystokininaemia that had had a pancreaticobiliary diversion (PBD) operation and sham operated rats served as controls. Fundectomised rats showed a significant increase in pancreatic weight and total DNA and protein content compared with sham operated rats. DNA flow cytometry showed a significantly higher ratio of tetraploid to diploid nuclei in pancreatic tissue after fundectomy than after sham operation. Mean values of all these variables were significantly lower after fundectomy than after PBD. Acidophilic atypical acinar cell foci of the pancreas were diagnosed in both fundectomised and PBD operated rats, but not in sham operated controls. The volume density and 3H-thymidine labelling index of the acidophilic atypical acinar cell foci were significantly lower after fundectomy than after PBD. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. In conclusion, fundectomy lasting about half of the life span in rats causes pancreatic hyperplasia and hypertrophy, as well as development of acidophilic atypical acinar cell foci. Although hypergastrinaemia is a prominent feature, it may not be the only factor responsible for this pancreaticotrophical effect of fundectomy.


Comparison of the exercise ECG and stress myocardial SPECT in detection of the significant coronary artery disease in the asymptomatic patients with diabetes mellitus type 2.
Diabetes mellitus is known to be a risk factor of the coronary heart disease even in the asymptomatic patients. Only a limited number of reports comparing the significance of different noninvasive stress tests in establishing the diagnosis of the advanced coronary lesions exists. The aim of the study was to compare the significance of 12-lead exercise ECG and the myocardial SPECT in order to detect the significant coronary heart disease in asymptomatic type 2 diabetics. 126 type 2 diabetic patients with negative history and no clinical or electrocardiographic signs of coronary heart disease were examined with the exercise ECG and the stress myocardial SPECT. The selective coronary angiography (SCG) was recommended to all patients with an abnormal SPECT or (and) a positive exercise ECG. The SCG was recommended to patients with equivocal results of the stress myocardial SPECT as well. 33 out of 126 examined patients (26.2%) had an abnormal, 33 equivocal and 60 normal stress myocardial SPECT. The exercise test could be evaluated in 99 examined patients (78%). 25 diabetics had positive test (19.8%). The correlation between the results of 2 tests was very good (p=0.0001). 38 patients had SCG, 24 with the abnormal SPECT, 13 with equivocal and 1 with normal SPECT. Out of these 20 patients had positive, 10 negative and 8 non-assessable exercise ECG. The relation between the presence of significant coronary stenosis (stenosis >70%) and the presence of abnormal stress myocardial SPECT was stronger (p=0.006) when compared with the positive exercise test (p=0.037). For the significant coronary stenosis the positive predictive value was 90% with the stress myocardial SPECT and 68% with the exercise ECG. The significance of the exercise ECG is lower predominantly due to high proportion of patients with non-assessable results. For the presence of significant coronary stenosis the positive predictive value of the stress myocardial SPECT is better than that of the exercise ECG. (Tab. 2, Ref: 25.)


Detection of anti-Toxoplasma gondii antibodies in carthorses in the metropolitan region of Curitiba, Paraná, Brazil.
Toxoplasma gondii, the agent for toxoplasmosis, has worldwide distribution. Horses normally play a secondary role in its life cycle, but movement around urban areas, feeding on grass and the increasing use of carthorses for gathering recyclable material in some urban areas of Brazil may increase their exposure to T. gondii infection. The aim of the present study was to investigate the frequency of anti-T. gondii antibodies in carthorses in the metropolitan region of Curitiba, PR. IgG antibodies against T. gondii were detected using the indirect fluorescence antibody test (IFAT) (titers ≥ 64). Seventeen (17.0%) of the 100 horses sampled were seropositive. There were no statistical differences in relation to sex (p = 0.28) or age (p = 0.15). Our findings suggest that carthorses are exposed to T. gondii infections and that no associations with age or sex exist.


Colchicine-Induced Rhabdomyolysis: Clinical, Biochemical, and Neurophysiological Features and Review of the Literature.
We report the case of a 46-years-old man with long-term asymptomatic hyperuricemia who started taking colchicine (0.5 mg/day) and allopurinol (100 mg/d) for normalization of biochemical values. After the third week of starting treatment, acute weakness was present; and by the fifth week, profound weakness in lower extremities and tenderness and cramps on thighs and calves with inability to climb stairs were also observed. Biochemical evaluation showed elevated muscle enzymes (creatinine kinase [CK] raised to five-folds its normal value) and electromyographic features were consistent with myopathy (at rest, fibrillations, positive sharp waves, high-frequency myotonic discharges; motor unit action potentials [MUAPs] of small amplitude, small duration, increased polyphasic Index and occasional satellite potentials; at maximal effort, interferential recruitment pattern with reduced amplitudes were observed). Normal motor and sensitive nerve conduction studies and normal late F-responses and H-reflex discarded neuropathy. Rapid improvement in muscle strength and prompt resolution of abnormal elevated muscle enzymes was observed after withdrawal of both medications. Colchicine is associated with some cases of myotoxicity but very small cases of colchicine-induced rhabdomyolysis are reported on the literature. Colchicine-induced rhabdomyolysis is related to the concomitant use of drugs (statins, steroids, erythromycin, and cyclosporine), renal, and/or hepatic impairment. To the best of our knowledge, this is an uncommon presentation of a case of colchicine-induced rhabdomyolysis reported in a patient without renal or hepatic dysfunction. Therefore, patients receiving colchicine even in the absence of renal insufficiency should be monitored for the development of myopathy and more rarely to rhabdomyolysis.


Purification and primary structure of two neuroactive peptides that cause bag cell afterdischarge and egg-laying in Aplysia.
Two neuroactive peptides, A and B, have been isolated from the atrial gland in the reproductive tract of Aplysia. Each of the two peptides is able to induce egg-laying behavior in recipient animals. In vitro recordings from the abdominal ganglion show that both peptides also trigger longlasting discharges in the bag cell neurons at concentrations around 0.1 muM. The peptides were purified by a combination of ammonium sulfate precipitation, agarose gel filtration, and cation exchange chromatography. Each peptide has 34 amino acid residues. Microsequencing together with carboxypeptidase Y degradation and analysis of tryptic peptides revealed the following sequence for peptide A: H-Ala-Val-Lys-Leu-Ser-Ser-Asp-Gly-Asn-Tyr-Pro-Phe-Asp-Leu-Ser-Lys-Glu-Asp-Gly -Ala-Gln-Pro-Tyr-Phe-Met-Thr-Pro-Arg-Leu-Arg-Phe-Tyr-Pro-Ile. Peptide B differs from A in only four positions. The first nine residues of B are: Ala-Val-Lys-Ser-Ser-Ser-Tyr-Glu-Lys-, whereas residues 10-34 of B are identical to those of A. The calculated M(r) of A is 3924 and that of B is 4032. The pI of peptide A as determined by isoelectric focusing in polyacrylamide gels is 7.9-8.1 and that of peptide B is 9.0-9.2. It is estimated that each atrial gland contains at least 150 mug of peptide A and 50 mug of B. Neither peptide resembles the egg-laying hormone isolated from bag cell neurons. It is postulated that the atrial gland peptides are released during copulation, and then by interacting with neuronal receptors in the head ganglia and pleuroabdominal connectives they cause the bag cells to afterdischarge, thereby releasing egg-laying hormone.


Sarcoid heart disease.
To this day the aetiology of sarcoidosis continues to elude definition. Partially as a consequence of this, little in the way of new therapies has evolved. The enigma of this condition is that, unusually for a disease with the potential for devastating consequences, many patients show spontaneous resolution and recover. Cardiac involvement can affect individuals of any age, gender or race and has a predilection for the conduction system of the heart. Heart involvement can also cause a dilated cardiomyopathy with consequent progressive heart failure. The most common presentation of this systemic disease is with pulmonary infiltration, but many cases will be asymptomatic and are detected on routine chest radiography revealing lymphadenopathy. Current advances lie in the newer methods of imaging and diagnosing this unusual heart disease. This review describes the pathology and diagnosis of this condition and the newer imaging techniques that have developed for determining cardiac involvement.


Identification of vortex structures in a cohort of 204 intracranial aneurysms.
An intracranial aneurysm (IA) is a cerebrovascular pathology that can lead to death or disability if ruptured. Abnormal wall shear stress (WSS) has been associated with IA growth and rupture, but little is known about the underlying flow physics related to rupture-prone IAs. Previous studies, based on analysis of a few aneurysms or partial views of three-dimensional vortex structures, suggest that rupture is associated with complex vortical flow inside IAs. To further elucidate the relevance of vortical flow in aneurysm pathophysiology, we studied 204 patient IAs (56 ruptured and 148 unruptured). Using objective quantities to identify three-dimensional vortex structures, we investigated the characteristics associated with aneurysm rupture and if these features correlate with previously proposed WSS and morphological characteristics indicative of IA rupture. Based on the Q-criterion definition of a vortex, we quantified the degree of the aneurysmal region occupied by vortex structures using the volume vortex fraction (vVF) and the surface vortex fraction (sVF). Computational fluid dynamics simulations showed that the sVF, but not the vVF, discriminated ruptured from unruptured aneurysms. Furthermore, we found that the near-wall vortex structures co-localized with regions of inflow jet breakdown, and significantly correlated to previously proposed haemodynamic and morphologic characteristics of ruptured IAs.


Evaluation of the neuroprotective, anticonvulsant, and cognition-improvement effects of apigenin in temporal lobe epilepsy: Involvement of the mitochondrial apoptotic pathway.
Cognitive deficit is a common problem in epilepsy. A major concern emergent from the use of antiepileptic drugs includes their side effects on learning and memory. Herbal medicine is considered a complementary and alternative therapy in epilepsy. Apigenin is a safe flavone with antioxidant properties. However, there is little information about the beneficial effect of apigenin on cognition in epilepsy. For evaluating the anticonvulsant effect of apigenin in the kainite temporal epilepsy model, apigenin was orally administered at 50 mg/kg for six days. Reference and working memory were examined via the Morris water maze and Y-maze task spontaneously. Results showed that apigenin had significant anticonvulsant activity (P<0.01) and restored the memory-deficit induced by kainic acid (P<0.05). Furthermore, apigenin significantly increased the number of living neurons in the hilus (P<0.001). Immunohistochemical analysis showed that apigenin reduced the release of cytochrome c (P<0.01), suggesting an inhibitory role in the intrinsic apoptotic pathway. These results suggest that apigenin restores memory impairment via anticonvulsant and neuroprotective activity.


Polygenic Risk and Chemotherapy-Related Subsequent Malignancies in Childhood Cancer Survivors: A Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study Report.
Chemotherapeutic exposures are associated with subsequent malignant neoplasm (SMN) risk. The role of genetic susceptibility in chemotherapy-related SMNs should be defined as use of radiation therapy (RT) decreases. SMNs among long-term childhood cancer survivors of European (EUR; N = 9,895) and African (AFR; N = 718) genetic ancestry from the Childhood Cancer Survivor Study and St Jude Lifetime Cohort Study were evaluated. An externally validated 179-variant polygenic risk score (PRS) associated with pleiotropic adult cancer risk from the UK Biobank Study (N > 400,000) was computed for each survivor. SMN cumulative incidence comparing top and bottom PRS quintiles was estimated, along with hazard ratios (HRs) from proportional hazards models. A total of 1,594 survivors developed SMNs, with basal cell carcinomas (n = 822), breast cancers (n = 235), and thyroid cancers (n = 221) being the most frequent. Although SMN risk associations with the PRS were extremely modest in RT-exposed EUR survivors (HR, 1.22; P = .048; n = 4,630), the increase in 30-year SMN cumulative incidence and HRs comparing top and bottom PRS quintiles was statistically significant among nonirradiated EUR survivors (n = 4,322) treated with alkylating agents (17% v 6%; HR, 2.46; P < .01), anthracyclines (20% v 8%; HR, 2.86; P < .001), epipodophyllotoxins (23% v 1%; HR, 12.20; P < .001), or platinums (46% v 7%; HR, 8.58; P < .01). This PRS also significantly modified epipodophyllotoxin-related SMN risk among nonirradiated AFR survivors (n = 414; P < .01). Improvements in prediction attributable to the PRS were greatest for epipodophyllotoxin-exposed (AUC, 0.71 v 0.63) and platinum-exposed (AUC,0.68 v 0.58) survivors. A pleiotropic cancer PRS has strong potential for improving SMN clinical risk stratification among nonirradiated survivors treated with specific chemotherapies. A polygenic risk screening approach may be a valuable complement to an early screening strategy on the basis of treatments and rare cancer-susceptibility mutations.


Self-Empowerment of Immigrant Latina Survivors of Domestic Violence: A Promotora Model of Community Leadership.
This article presents the results of a self-empowerment leadership intervention program for Latina immigrant survivors of domestic violence in Atlanta, Georgia. It builds on the literature base of the Promotora model, a public health model using peer information sharing as a tool for health promotion. This study used an embedded mixed-methods design with quantitative and qualitative components to evaluate the impact of a peer community leadership program called Líderes Results of single-subject analyses show that the participants experienced change in three components of self-empowerment: intrapersonal, interactional, and behavioral. The qualitative findings revealed that they overcame fear and gained knowledge as well as a sense that they could promote change in their community. These findings add support to a growing literature base that demonstrates how peer model programs can not only positively influence the well-being of the communities they serve but also have transformative effects on peer leaders themselves. Study findings can also inform future efforts to empower survivors through promotora approaches specifically in the context of domestic violence prevention.


Calcium-dependent potassium exchange in human red cell ghosts.
1. The properties of the Ca-dependent K transport system of human red cell ghosts have been examined under equilibrium exchange conditions. 2. K transport is stimulated half-maximally by about 0-4muM-Ca2i+ or 5muM-Sr2i+, but much higher concentrations of Ba2i+ give only slight stimulation. Mg is a weak antagonist to Ca. 3. The free Ca2+ concentration in human red cells is estimated to be below 0-25muM. 4. The curve relating the rate of K transport to the intracellular Ca2+ concentration is complicated and suggests that internal Ca acts at three or more sites. 5. K, Rb and possibly Cs ions are transported by the Ca-dependent system. Under comparable conditions the relative rates are 1(K):1-5(Rb): less than 0-05(Cs). 6. No Ca-dependent transport of Na, Li or choline could be detected. If Na is transported, it must be at less than 1/40 of the rate of K. 7. The rate of K transport is almost linearly related to the K concentration in the 0-200 mM range, but the curve is sigmoid close to the origin. 8. Intracellular, but not extracellular Na inhibits K transport, in a way that suggests competition with K at more than one site. 9. These results suggest that the transport system has a complex mechanism.


Differential release of calcitonin gene-related peptide and neuropeptide Y from the isolated heart by capsaicin, ischaemia, nicotine, bradykinin and ouabain.
The influence of various drugs as well as total ischaemia on the outflow of calcitonin gene-related peptide (CGRP), which is present in sensory nerves, and neuropeptide Y (NPY), which is co-stored with noradrenaline (NA), from the isolated guinea-pig heart, was studied in vitro. Capsaicin exposure and total ischaemia for 5-30 min induced a Ca2+-dependent increase in the outflow, suggesting release, of CGRP- but not NPY-like immunoreactivity (LI) from the heart. When characterized by high performance liquid chromatography (HPLC), the CGRP-LI present in heart extracts and the released CGRP-LI by capsaicin eluted in a major peak corresponding to synthetic CGRP. Incubation with morphine, indomethacin or reserpine pretreatment did not influence the capsaicin-evoked release of CGRP-LI. Capsaicin pretreatment depleted the cardiac content of CGRP-LI but not NPY-LI. The increase in perfusate volume observed after 30 min ischaemia in controls was reduced after capsaicin pretreatment. Nicotine exposure induced release of CGRP- as well as NPY-LI in a concentration- and Ca2+-dependent manner. The increased outflow of NPY-LI was not influenced by capsaicin pretreatment. Among other agents tested, bradykinin and ouabain caused increased outflow of CGRP but not of NPY-LI. Noradrenaline, tyramine, histamine, vasopressin, alpha,beta methylene ATP, ATP or adenosine induced changes in cardiac contractility or flow but did not evoke any detectable release of CGRP- or NPY-LI. In conclusion, the release of multiple neuropeptides can be studied in combination with contractile recordings using the isolated perfused guinea-pig whole heart preparation. Activation of cardiac sensory nerves by capsaicin, nicotine, bradykinin and ouabain, as well as ischaemia, induced release of CGRP while nicotine also evoked NPY release.


[Ectopic ACTH-syndrome caused by neuroendocrine tumor of lung].
Ectopic ACTH-syndrome is a relatively rare neuroendocrine disease. It is characterized by hypercortisolemia-associated severe complications that justifies need for timely diagnosis and radical therapy. Case report of young patient with ACTH-producing lung tumor is presented. There was 1-year diagnostic search on background of endogenous hypercorticism. Treatment resulted severe postoperative adrenal insufficiency that demonstrates current difficulties in management of these patients.


Cytosolic and Nuclear Co-localization of Betalain Biosynthetic Enzymes in Tobacco Suggests that Betalains Are Synthesized in the Cytoplasm and/or Nucleus of Betalainic Plant Cells.
Betalains replace anthocyanins as color pigments in most families of Caryophyllales. Unlike anthocyanins, betalains are derived from tyrosine via three enzymatic steps: hydroxylation of L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA; step 1), and conversion of L-DOPA to betalamic acid (step 2), and to cyclo-DOPA (cDOPA; step 3). The principal enzymes responsible for these reactions have been elucidated at the molecular level, but their subcellular localizations have not been explored; hence, the intracellular compartments wherein betalains are biosynthesized remain unknown. Here, we report on the subcellular localization of these principal enzymes. Bioinformatic predictors and N- and C-terminal GFP tagging in transgenic tobacco, showed that Beta vulgaris CYP76AD1 which mediates both steps 1 and 3, DODA1 that catalyzes step 2, and CYP76AD6 which also mediates step 1, were similarly localized to the cytoplasm and nucleus (although the P450s were also weakly present in the endoplasmic reticulum). These two compartments were also the principal locations of Mirabilis jalapa cDOPA5GT. The cytoplasmic and nuclear co-localization of these key enzymes in tobacco suggests that betalains are biosynthesized in the cytoplasm and/or nucleus of betalain-containing plant cells. Elucidation of the subcellular compartmentation of betalain biosynthesis will facilitate the bioengineering of the betalain biosynthetic pathway in non-betalain-containing plants.


Size Reduction Efficiency of Alpha-Mangostin Suspension Using High-Pressure Homogenization.
In this study, we aimed to investigate the effects of stabilizers and processing parameters on the size reduction of alpha-mangostin (AMG) using high-pressure homogenization (HPH). The solubility of AMG in various stabilizers was studied. Selected stabilizers were used to prepare AMG suspensions by HPH under different conditions. After HPH, the particle size of AMG suspensions with stabilizers significantly decreased to microns. Percent size reduction efficiency of all AMG suspensions with each stabilizer increased with the increase in the number of homogenization cycles. Sodium lauryl sulfate and poloxamer188 provided a greater extent of particle size reduction than polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer. AMG suspensions with binary stabilizers at higher pressure were also prepared. The use of high pressure increased percent size reduction efficiency.


Bis(merocyanine) Homo-Folda-Dimers: Evaluation of Electronic and Spectral Changes in Well-Defined Dye Aggregate Geometries.
A series of three bis(merocyanine) dyes comprising chromophores of different conjugation lengths has been synthesized and the intramolecular aggregation process was investigated by UV/Vis absorption spectroscopy. The spectral changes observed upon variation of the solvent polarity reveal a folding process resulting in a cofacial π-stack of two chromophores with a decrease of the aggregation tendency with increasing chromophore length and solvent polarity. Solvent-dependent UV/Vis studies of the monomeric reference dyes show a significant increase of the polyene-like character for dyes with longer polymethine chains in nonpolar solvents, which is reversed upon aggregation due to the polarizability effect of the adjacent chromophore within the dye stack. The pronounced hypsochromic shift of the absorption band observed upon aggregation indicates strong coupling of the dyes' transition dipole moments, which was confirmed by quantum-chemical analysis.


T cells bind to cytokine-activated endothelial cells via a novel, inducible sialoglycoprotein and endothelial leukocyte adhesion molecule-1.
The action of human rIL-1 beta on confluent, quiescent monolayers of human umbilical vein endothelial cells (HUVEC) has been studied for the induction of new membrane proteins. Two approaches have been taken. The first is a quantitative two-dimensional gel analysis of [35S]cysteine-labeled membrane proteins of HUVEC with and without cytokine treatment. This analysis indicates that there are a restricted number of new membrane proteins synthesized in the first 6 h of IL-1 treatment, on the order of 19 out of a total of over 600 detectable proteins. Second, we have prepared two mAb (1E7 and 2G7) to different epitopes of a major inducible sialoglycoprotein with molecular mass of 114 kDa and an isoelectric point of 4.6 to 4.8. These antibodies were compared with two additional antibodies, 3B7 and 7A9, which were shown to react with the endothelial leukocyte adhesion molecule-1 (ELAM-1) protein as expressed in COS cells. The 1E7/2G7 protein is distinct from ELAM-1, based upon biochemical comparisons as well as the inability of the 1E7 and 2G7 antibodies to react with ELAM-1-transfected COS cells. The protein defined as 1E7/2G7 is neither expressed constitutively nor in an inducible manner on PBMC, granulocytes, platelets, fibroblasts, or keratinocytes. The 7A9 and 3B7 antibodies are shown to block granulocyte binding to IL-1-activated HUVEC. The 2G7 antibody is effective at inhibiting the binding of T cells but not granulocytes to IL-1-activated endothelium, suggesting this new protein is an adhesion protein that may be active in vivo in T cell-endothelial cell adhesion-related events such as inflammation or lymphocyte recirculation. In addition, T cells were shown to utilize the ELAM-1 protein in binding to cytokine-activated HUVEC. Antibodies directed to both proteins had additive effects on inhibition of T cell adhesion.


Pharmacokinetics and Pharmacogenomics of Bupropion in Three Different Formulations with Different Release Kinetics in Healthy Human Volunteers.
The purpose of this pharmacokinetics (PK) study was to investigate whether different release kinetics from bupropion hydrochloride (HCl) immediate release (IR), sustained release (SR), and extended release (ER) formulations alter its metabolism and to test the hypothesis that the unsuccessful bioequivalence (BE) study of the higher strength (300 mg) of bupropion HCl ER tablets based on the successful BE study of the lower strength (150 mg) was due to metabolic saturation in the gastrointestinal (GI) lumen. A randomized six-way crossover study was conducted in healthy volunteers. During each period, subjects took a single dose of IR (75/100 mg), SR (100/150 mg), or ER (150/300 mg) formulations of bupropion HCl; plasma samples for PK analysis were collected from 0-96 h for all formulations. In addition, each subject's whole blood was collected for the genotyping of various single-nucleotide polymorphisms (SNPs) of bupropion's major metabolic enzymes. The data indicates that the relative bioavailability of the ER formulations was 72.3-78.8% compared with IR 75 mg. No differences were observed for ratio of the area under the curve (AUC) of metabolite to AUC of parent for the three major metabolites. The pharmacogenomics analysis suggested no statistically significant correlation between polymorphisms and PK parameters of the various formulations. Altogether, these data suggested that the different release kinetics of the formulations did not change metabolites-to-parent ratio. Therefore, the differing BE result between the 150 and 300 mg bupropion HCl ER tablets was unlikely due to the metabolic saturation in the GI lumen caused by different release patterns.


[Anatomy and lesions of the coronary system. Comparative data on 100 consecutively examined patients under 35 and over 45].
The aim of the present study was to search for a causal factor of anatomical nature: the shortness of left main coronary (LMC) in two patient groups: a group of 26 patients (males) below age 35, (mean age +/- S.D.: 31 +/- 3 years) and a group of 74 patients (71 males), all over the age of 45, (mean age +/- S.D. 54 +/- 10 years). A comparison group of 32 patients without coronary disease, with normal coronary arteries, (mean age +/- S.D.: 51 +/- 11 years) was identified. The computed mean length of the LMC was 9.92 +/- 3.26 mm (extreme values 2-16) in the young age group, was 11.70 +/- 3.10 mm (extreme values 2-17) (p less than 0.02) in the older age group with coronary artery disease, and was 11.85 +/- 2.55 mm (extreme values 3-21) (p = n.s.) in the group with normal coronary arteries. The mean length of the LMC in the patient group (100 patients) with coronary disease was 11.24 mm. Short stems were noticed in 14 of 26 patients (54 p. 100) in the young group, and in 22 of 74 patients (30 p. 100) in the second group, and there was a statistically significant difference between the proportions of short stems in these two groups (p less than 0.05). The mean length of LMC in the controls (Group III; 11.85) was not significantly different from that in Group II, namely 11.70.(ABSTRACT TRUNCATED AT 250 WORDS)


Stereochemical assignment of fusiccocadiene from NMR shielding constants and vibrational circular dichroism spectroscopy.
The absolute configuration (AC) of the common precursor of the fusicoccane family of terpenoids, fusicocca-2,10(14)-diene (FCdiene), had only been deduced by a lengthy total synthesis, or indirectly from crystal structures of fusicoccin A. However, in particular the AC determinations based on downstream products of the terpene synthase intrinsically overlook potential epimerization reactions. In this contribution, we confirm the relative stereochemistry of FCdiene by comparison of experimental and predicted 13 C-NMR chemical shifts, and finally determine the absolute configuration from an analysis of its infrared and vibrational circular dichroism spectra.


Observation of Coexistence of Yu-Shiba-Rusinov States and Spin-Flip Excitations.
We investigate the spectral evolution in different metal phthalocyanine molecules on NbSe2 surface using scanning tunnelling microscopy (STM) as a function of the coupling with the substrate. For manganese phthalocyanine (MnPc), we demonstrate a smooth spectral crossover from Yu-Shiba-Rusinov (YSR) bound states to spin-flip excitations. This has not been observed previously and it is in contrast to simple theoretical expectations. We corroborate the experimental findings using numerical renormalization group calculations. Our results provide fundamental new insight on the behavior of atomic scale magnetic/SC hybrid systems, which is important, for example, for engineered topological superconductors and spin logic devices.


Prevalence and correlations of temporomandibular disorders in Northern Jordan using diagnostic criteria axis I.
The aim of the present study was to document the prevalence and possible correlations of temporomandibular disorders (TMD) in a sample of participants from Northern Jordan. A total of 368 adult participants were consecutively selected from visitors to a major health facility in Northern Jordan and examined according to the diagnostic criteria (DC) for TMD (DC/TMD) protocol. Patients with conditions that could interfere with TMD diagnosis were excluded. Pearson correlation and analysis of variance statistical tests were applied. Statistical significance was set at P ≤ 0.05, with a 95% confidence interval. A total of 98 patients (26.7%) had 1 TMD diagnoses; 60 participants (16.3%) had a pain-related TMD diagnosis, 48 (13%) had intra-articular joint disorders (IAD), and 16 had both pain-related TMD and IAD. In addition, six (1.6%) participants were found to have degenerative joint disease. Females were found to have a higher prevalence of pain-related TMD diagnoses (r = 0.111, P = 0.034) and headache (r = 0.129, P = 0.013) than males. Clicking was positively related to both pain-related TMD (r = 0.154, P = 0.003) and IAD (r = 0.576, P = 0.000). The frequency of TMD and related features was reported in a Northern Jordanian population using DC/TMD for the first time, and the results are comparable to other populations in similar study settings.


Using a genetically targeted sensor to investigate the role of presenilin-1 in ER Ca2+ levels and dynamics.
The ER plays a fundamental role in storing cellular Ca(2+), generating Ca(2+) signals, and modulating Ca(2+) in both the cytosol and mitochondria. Genetically encoded Ca(2+) sensors can be explicitly targeted to the ER to directly define Ca(2+) levels and monitor fluxes of Ca(2+) within this organelle. In this study we use an ER-targeted Ca(2+) sensor to define both the level and dynamics of ER Ca(2+) in cells expressing mutant presenilin proteins. Growing evidence suggests the enigmatic presenilin-1 plays a role in regulating ER Ca(2+). Presenilin-1 was initially identified in a screen for genetic causes of inherited familial Alzheimer's disease (fAD). The connection between presenilin-1, calcium regulation, and Alzheimer's disease may provide the key to understanding the long-observed, but poorly understood, link between Alzheimer's disease and Ca(2+) dysregulation. In this study we examined seven fAD-causing mutations in presenilin-1 to define how they influence ER Ca(2+) levels and dynamics. We observed that some, but not all, mutations in PS1 decrease the level of Ca(2+) within the ER and this difference depends on the enzymatic activity of PS1. Two mutations tested altered the kinetics of Ca(2+) release from the ER upon ATP stimulation, resulting in faster spiking. Combined, these results indicate that mutations in PS1 can alter the balance of Ca(2+) in cells and have the potential to influence the nature of Ca(2+) signals.


Culture and maintenance of Agrobacterium strains.
As aerobic chemoorganotrophs, most Agrobacterium strains will grow on a wide range of complex and defined media. Methods commonly used for the culture and storage of other chemoorganotrophs will usually work for agrobacteria as well. Problems with culture or strain maintenance will occur more frequently because of careless technique than because of strain difficulties. Here we describe a few of the complex and defined media that have been successfully used in the growth of agrobacteria including some that are semiselective for agrobacteria. Finally, we present methods suitable for short- and long-term storage of Agrobacterium strains.


Fertility preservation in male patients subjected to chemotherapy; innovative approaches for further progress.
About 4% of male patients with cancer are under the age of 35 years. With the current increase in efficacy and safety of therapies, a growing number of young adults can achieve long-term survival. In male patients receiving systemic chemotherapy and or bone marrow transplantation, a permanent loss of fertility is a common adverse effect. The only possibility to preserve the patient's fertility is to spare the gametes or gamete-forming cells from the chemotherapeutic effect. In adults, this can be achieved by the cryopreservation of spermatozoa with the subsequent application of assisted reproductive technology. Sperm cryopreservation is currently performed using slow-rate cryopreservation as a standard method, in which sperm cells are incubated with a cryoprotective medium and slowly subjected to hypothermia in liquid nitrogen (LN) vapor before they are placed in LN. Another technique called vitrification relies on the direct placement of the cells into LN, after being suspended in a vitrification medium. Many studies compared the clinical outcomes of both techniques and revealed equivalent results. This paper sheds light on some innovative approaches for further progress.


'Striving for freedom or remaining with what is well-known': a focus-group study of self-management among people with type 1 diabetes who have suboptimal glycaemic control despite continuous subcutaneous insulin infusion.
Continuous subcutaneous insulin infusion (CSII) treatment is beneficial for obtaining glycaemic control for many persons with type 1 diabetes mellitus (T1DM). Still, some individuals do not obtain improved HbA1C levels despite CSII treatment, and there is a lack of evidence regarding how psychosocial factors may influence glycaemic control. Thus, we aimed to explore the attitudes and experiences of self-management among people with T1DM and suboptimal glycaemic control despite CSII treatment. A qualitative inductive design was applied, and four FGDs were performed with 37 adult men and women of various ages and duration of T1DM. All participants had suboptimal glycaemic control despite CSII treatment. Transcripts were analysed using qualitative manifest and latent content analysis. The themes Searching for freedom and flexibility and Preferring safety and the well-known illustrated the divergent psychosocial strategies adapted, which both resulted in suboptimal glycaemic control. The technical devices and their effects on glycaemic levels may be challenging to understand and adjust to fit people's lifestyles. The rapid advances of technology devices in diabetes care can potentially change peoples' lives, but is the educational support developing as fast? Multifaceted web-based education of high quality, including tailored support with a person-centred focus, is more important than ever before as the need for technical knowledge and understanding may put further disease burdens to patients with T1DM on CSII treatment.


Thunderclap headache.
Thunderclap headache refers to an excruciating headache of instantaneous onset. It occurs as suddenly and unexpectedly as a "clap of thunder." Patients with thunderclap headache may have normal neurologic examination results and normal computed tomographic brain scans, even if they have serious underlying pathology. This has created confusion regarding nosology and the nature and extent of the diagnostic evaluation, which this article discusses.


Alteration of serum miR-206 and miR-133b is associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
The alteration of microRNA (miRNA) expression plays an important role in chemical carcinogenesis. Presently, few reports have been published that concern the significance of circulating miRNAs in lung carcinogenesis induced by environmental carcinogens. The purpose of this study was to identify serum miRNAs that could be associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Male F344 rats were systemically administered with NNK. The rat serum differential expression profiles of miRNAs were analyzed by small RNA solexa sequencing. Using quantitative real-time PCR, the differentially expressed serum miRNAs were identified in each individual rat. Serum miR-206 and miR-133b were selected for further identification in rat serum at different stages of lung carcinogenesis; we detected the levels of serum miR-206 and miR-133b in lung cancer tissues induced by NNK. NNK causes significant alteration of serum miRNA expression. Compared to the control group, serum miR-206 and miR-133b were significantly up-regulated in the early stage of NNK-induced lung carcinogenesis. miR-206 and miR-133b exhibited low-expression in lung cancer tissues. Our results demonstrate that lung carcinogen NNK exposure changes the expression of serum miRNAs. Serum miR-206 and miR-133b could be associated with lung carcinogenesis induced by NNK.


Two-dimensional clusters of solitary structures in driven optical cavities.
Using analytical and numerical approaches we study clusters of the two-dimensional localized structures of light excited in the externally driven optical cavities. Stability and instability properties of clusters of two, three, and four structures are analyzed in detail. We develop a technique for calculation of the expression for the interaction potential through modified Bessel functions that has applicability going beyond the model under consideration. Qualitative differences between stability properties of triangular and square structures are found that emphasize the role of diagonal interactions in the latter.


Standard versus Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Prospective Randomized Study.
Symptomatic spondylolisthesis patients may benefit from surgical decompression and stabilization. The standard (S) technique is a transforaminal lumbar interbody fusion (TLIF). Newer, minimally invasive (MI) techniques seem to provide similar results with less morbidity. We enrolled patients with at least 6 months of symptoms and image-confirmed low-grade spondylolisthesis, at a single academic institution, between 2011 and 2015. The patients were randomized to either S or MI TLIF. The primary outcome measure was the Oswestry Disability Index (ODI) improvement at 1 year. Secondary outcome measures included length of operation, estimated blood loss, length of hospitalization, and fusion rates at 1 year. Forty patients were enrolled in each group. The differences in mean operative time and estimated blood loss were not statistically significant between the two groups. The patients were discharged after surgery at 4.12 days for the S TLIF group and 1.92 days for the MI TLIF group. The ODI improvement was similar and statistically significant in both groups. The fusion was considered solid in 36 (90%) of patients at 1 year in both groups. In conclusion, the two techniques provided similar clinical and radiological outcomes at 1 year. The patients undergoing MI TLIF had a shorter hospital stay. This trial is registered with NCT03155789.


Acquired sensory control of satiation in man.
Lean male and female subjects who had been taking their meals as usual were given a 100 ml drink of starch immediately before a sandwich lunch. In the training phase,65 per cent starch was given before lunches which included a yoghurt-based dessert of one flavour and 5 per cent starch was given before another flavour. Subjects who initially ate lunches of similar size following the two drinks began after several pairings to take larger lunches following dilute starch than following concentrated starch. In extinction tests, identical 35 per cent starch drinks were given before lunches including desserts of either flavour. Lunches including the flavour hitherto paired with dilute starch remained larger than lunches including the other flavour, at least initially in extinction. Some of the difference in intake occurred in the dessert itself. None was attributable to differences in the early stage of the lunches. These results extend to man recent demonstrations that the satisfying power of a foodstuff is in part acquired by association of its sensory characteristics with some consequence of ingesting the nutrients which are consistently taken with or in that food. This consequence may be rapid intestinal absorption of glucose during or shortly after sensory input. The nature of the intake-suppressing response remains to be determined.


The role of BETA2/NeuroD1 in the development of the nervous system.
BETA2/NeuroD1 is a member of the basic helix-loop-helix (bHLH) transcription factor family, which has been shown to play a major role in development of the nervous system and formation of the endocrine system. Gain-of-function studies have indicated that BETA2/NeuroD1 is important for the neurogenesis of Xenopus embryos and several neurogenic cell lines. Disruption of the gene encoding BETA2/NeuroD1 leads to severe abnormalities of the developing mouse central nervous system as well as the peripheral nervous system. The focus of this article is on the recent progress in understanding the role of BETA2/NeuroD1 in the development of the nervous system.


A 25-year surveillance of disseminated Bacillus Calmette-Guérin disease treatment in children in Southern Iran.
Disseminated Bacillus Calmette-Guérin (BCG) disease is one of the most serious complications of BCG vaccination, mainly among immunocompromised children with high morbidity and mortality.Currently, there is no any consensus with regard to the standard regimen of antituberculosis (anti-TB) agents and duration of treatment in healthy or immunocompromised host in children. The aim of this study is to investigate the effect of various combination treatment strategies for disseminated BCG disease in children.In this cross-sectional study, the outcome of 3 different combination protocols was investigated in 59 patients.All patients were younger than 6 years old. Both possible immunocompetent and proven immunodeficient children were included in a period of 25 years (1991-2014) in a Nemazee referral teaching hospital.The minimum age was 1 month and the maximum was 60 months. The average age of patients was 8 months (8.26 ± 9.73). Out of 59 cases, 32 (54.2%) were female and 27 (45.8%) were male. Based on the primary work up, 52.5% of cases were classified as definite immunodeficient and 47.5% were classified as possible immunocompetent. Overall mortality rate was 50.8%. Mortality rate of disseminated BCG disease in immunocompetent and immunodeficient children was 28.6% and 71%, respectively. The mortality rate was not statistically different between patients treated with different treatment protocols. These results were not affected by immune status and the type of immunodeficiency.More than 2 anti-TB drugs combination will not change outcome of patient with disseminated BCG disease.


Different classes of antibody activities to Trichosporon cutaneum antigen in summer-type hypersensitivity pneumonitis by enzyme-linked immunosorbent assay.
To assess the diagnostic value of antibody activities to Trichosporon cutaneum antigen in patients with summer-type hypersensitivity pneumonitis in Japan, we measured the serum IgG, IgA, and IgM antibodies to saline-soluble antigen of homogenized T. cutaneum cells by enzyme-linked immunosorbent assay (ELISA). The IgG antibody activity was observed in serum samples from 25 (83%) of the 30 patients and in 9 (82%) of the 11 asymptomatic family members. The IgA antibody activity was found in 25 (83%) of the patients but in only 3 (27%) of asymptomatic family members. Unexpectedly, we found no significant correlation between the IgG and IgA antibody activities to the same antigen in individual patients. Moreover, although the IgG antibody activity was related to the precipitating antibody, the IgA antibody activity was not. The IgM antibody activity by ELISA was found in only 5 (17%) of the patients. The IgG+IgA+IgM antibody activity was demonstrated in 27 (90%) of the 30 patients, and of 3 serum samples that were found negative by the ELISA method, 2 were positive by the IFA method. We conclude that the detection of the serum IgG and IgA antibody activities to T. cutaneum antigen by ELISA is a simple and useful serodiagnostic test for summer-type hypersensitivity pneumonitis. Measurement of the IgA antibody activity is especially helpful in discriminating symptomatic from asymptomatic family members.


Perspectives on the Use of Liquid Extraction for Radioisotope Purification.
The reliable and efficient production of radioisotopes for diagnosis and therapy is becoming an increasingly important capability, due to their demonstrated utility in Nuclear Medicine applications. Starting from the first processes involving the separation of 99mTc from irradiated materials, several methods and concepts have been developed to selectively extract the radioisotopes of interest. Even though the initial methods were based on liquid-liquid extraction (LLE) approaches, the perceived difficulty in automating such processes has slowly moved the focus towards resin separation methods, whose basic chemical principles are often similar to the LLE ones in terms of chelators and phases. However, the emerging field of flow chemistry allows LLE to be easily automated and operated in a continuous manner, resulting in an even improved efficiency and reliability. In this contribution, we will outline the fundamentals of LLE processes and their translation into flow-based apparatuses; in addition, we will provide examples of radioisotope separations that have been achieved using LLE methods. This article is intended to offer insights about the future potential of LLE to purify medically relevant radioisotopes.


Expressing patterns of p16 and CDK4 correlated to prognosis in colorectal carcinoma.
To describe the correlation between immunostaining patterns of p16 and CDK4 and prognosis in colorectal carcinoma. Paraffin sections of 74 cases of colorectal carcinoma were analysed immunohistochemically for expression of p16 and CDK4 proteins. Most carcinomas showed stronger p16 and CDK4 immunostaining in the cytoplasm than the adenomas or the adjacent normal mucosa. Strong immunostaining of p16 was a predictor for better prognosis whereas strong cytoplasmic immunostaining of CDK4 was a predictor for poor prognosis. Both p16 and CDK4 immunostainings were correlated with histological grade or Dukes' stage. These results support the experimental evidence that interaction of expression of p16 and CDK4 may play an important role in the Rb/p16 pathway, and the expression patterns of CDK4 and p16 may be imperative in the development of colorectal carcinoma, thus becoming a new prognostic marker in colorectal cancer.


[Study of impulsivity in rats under conditions of choice between food reinforcements of different values].
Rat behavior was studied under conditions "with the right to choose the values of reinforcements depending on the time delay of its receipt". Rats were placed in a chamber equipped with two retractable pedals, pressing one of which provided a small portion of food (1 pellet), and pressing the second pedal was followed by the delivery of more valuable food (4 pellets), but delayed reinforcement. Rats preferring small reinforcement without the delay were considered as "impulsive" and rats choosing more valuable delayed reinforcement were considered as "self-controlling". Influence of the delay duration and change in the level of motivation on the pedal pressing was studied in both groups of rats. Preference in the selection of the pedal, latency of pressing the pedal and the number of omitted reactions were estimated. It was found that "impulsive" animals more rapidly pressed the pedal and less frequently omitted trials than "self-controlling" rats. After the increase in the delay duration up to 7 seconds, rats stopped choosing the pedal with the delayed reinforcement. Increased food motivation shifted the behavior of rats to "self-control", whereas rats after feeding preferred less valuable immediate reinforcement.


Effect of Extraction Methods on Antioxidant Activity of Papery Skin Extracts and Fractions of Maja Cipanas Onion (Allium cepa L. var. ascalonicum).
Extraction can be carried out at ambient temperature or high temperature to accelerate the extraction process of secondary metabolites from simplicia. This study aimed to determine the effectiveness of extraction methods on antioxidant activity of secondary metabolites of papery skin extracts and fractions of Maja Cipanas onion (Allium cepa L. var. ascalonicum). Extraction methods were maceration, percolation, reflux, and Soxhlet method, and then, concentrated extracts were fractionated by liquid-liquid extraction based on the polarity of secondary metabolites. Antioxidant activity was determined by the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. The phytochemical screening showed that onion papery skin contained alkaloids, polyphenols, flavonoids, and tannins. The IC50 value of the extract, ethyl acetate fraction, and water fraction of the four extraction methods in the concentration range 25-400 μg/mL were in the range of 55.62-107.08, 31.31-84.06, and 126.05-139.82 μg/mL, respectively, while the IAA value was in the ranges of 0.25-0.49, 0.32-0.86, and 0.19-0.21, respectively. Variation in IC50 and IAA values indicate that the extraction method affects antioxidant activity, due to extracted secondary metabolites from simplicia. The highest antioxidant activity was an ethyl acetate fraction by the reflux method, while the lowest was water fraction by the percolation method.


Markerless Escherichia coli rrn Deletion Strains for Genetic Determination of Ribosomal Binding Sites.
Single-copy rrn strains facilitate genetic ribosomal studies in Escherichia coli. Consecutive markerless deletion of rrn operons resulted in slower growth upon inactivation of the fourth copy, which was reversed by supplying transfer RNA genes encoded in rrn operons in trans. Removal of the sixth, penultimate rrn copy led to a reduced growth rate due to limited rrn gene dosage. Whole-genome sequencing of variants of single-copy rrn strains revealed duplications of large stretches of genomic DNA. The combination of selective pressure, resulting from the decreased growth rate, and the six identical remaining scar sequences, facilitating homologous recombination events, presumably leads to elevated genomic instability.


[The histological picture of CRF in kidney grafts].
The most common immunological causes of delayed renal function failure in kidney grafts are recurrent glomerular disease, de novo glomerulonephritis, and chronic cellular or antibody-mediated rejection. Glomerulonephritis can recur any time in the natural history of renal allografts, with the same morphological features of the disease occurring in the native kidney. It has a frequency varying from 100% to 1% and a generally favorable prognosis with the exception of FSGS, SHU and diabetic glomerulosclerosis. The most frequent glomerular diseases to occur de novo in the kidney graft are membranous glomerulopathy, antiglomerular basement membrane disease in patients with Alport's syndrome, and nephrotic syndrome of the Finnish type with antinephrin antibodies in patients with NPHS1 gene mutations. Chronic rejection, including chronic transplant arteriopathy and chronic transplant glomerulopathy, is the cause of renal failure in up to 20% of kidney grafts and may occur as early as a few months after transplant.


[Sleep behavior and problems in children and adolescents of a psychiatric day clinic sample: results and requirements for systematic diagnostic].
Sleep behavior and problems in children and adolescents of a psychiatric day clinic sample: results and requirements for systematic diagnostic Abstract. Sleep disorders are common in adults as well as children and adolescents. Children and adolescents in psychiatric treatment (CAP) are especially affected by sleep problems. Cognitive behavioral therapy represents the first-line treatment, preceded by a standardized procedure for sleep diagnostics. To date, no study has investigated sleep behavior in CAP day clinics in Germany. In this study, N = 46 children/adolescents receiving CAP treatment in a day clinic completed a sleep diary (7 days) and a sleep anamnesis scheme with the help of their parents, and their sleep behavior was assessed by a clinician. Furthermore, a parent- and a self-report questionnaire plus a clinical assessment of the mental disorders in the children/adolescents were collected. 52 % of the children/ adolescents exhibited sleep disorders or sleep abnormalities (= sleep disorder symptoms in the context of comorbid disorders), in particular problems falling asleep or to falling asleep and sleeping through the night (26 %). In addition, 33 % reported having nightmares. Their sleep behavior correlated significantly with their external behavior problems (r = .38 .61, p = .02-.04); their sex (female: p = .01-≤ .001, |d| = 1.57-2.50) and their age (older: p = .05, |d| = .78) also significantly influenced sleep behavior. Particularly external behavior problems were associated with sleep problems in this day-care population. In summary, a multi-method-multi-informant procedure should be established for the systematic diagnostics of sleep abnormalities, together with individualized cognitive-behavioral therapy of sleep problems, especially in patients with external behavior problems.


Cytotoxic activity of proteins isolated from extracts of Corydalis cava tubers in human cervical carcinoma HeLa cells.
Corydalis cava Schweigg. & Koerte, the plant of numerous pharmacological activities, together with the studied earlier by our group Chelidonium majus L. (Greater Celandine), belong to the family Papaveraceae. The plant grows in Central and South Europe and produces the sizeable subterraneous tubers, empty inside, which are extremely resistant to various pathogen attacks. The Corydalis sp. tubers are a rich source of many biologically active substances, with the extensive use in European and Asian folk medicine. They have analgetic, sedating, narcotic, anti-inflammatory, anti-allergic and anti-tumour activities. On the other hand, there is no information about possible biological activities of proteins contained in Corydalis cava tubers. Nucleolytic proteins were isolated from the tubers of C. cava by separation on a heparin column and tested for DNase activity. Protein fractions showing nucleolytic activity were tested for cytotoxic activity in human cervical carcinoma HeLa cells. Cultures of HeLa cells were conducted in the presence of three protein concentrations: 42, 83 and 167 ng/ml during 48 h. Viability of cell cultures was appraised using XTT colorimetric test. Protein fractions were separated and protein bands were excised and sent for identification by mass spectrometry (LC-ESI-MS/MS). The studied protein fractions showed an inhibiting effect on mitochondrial activity of HeLa cells, depending on the administered dose of proteins. The most pronounced effect was obtained with the highest concentration of the protein (167 ng/ml) - 43.45 ± 3% mitochondrial activity of HeLa cells were inhibited. Mass spectrometry results for the proteins of applied fractions showed that they contained plant defense- and pathogenesis-related (PR) proteins. The cytotoxic effect of studied proteins toward HeLa cell line cells has been evident and dependent on increasing dose of the protein. The present study, most probably, represents the first investigations on the effect of purified PR proteins from tuber extracts of a pharmacologically active plant on cell lines.


Comparisons of motivation, health behaviors, and functional status among elders in residential homes in Korea.
This study compared the changes in health behaviors, motivation, and functional status between motivation enhancement exercise-program participants and program dropouts over 6 months. A total of 73 older adults living in residential homes participated in the study. Face-to-face interviews were conducted at pretest and then at 10 weeks and 6 months in the program. The participants exercised using traditional Korean dance movements for 50 min, 4 times per week, for 6 months. The subjects were classified as participants or dropouts by using a cutoff attendance rate of 80%. Repeated ANOVA revealed the following results over 6 months: 1 The motivation to perform health behaviors, especially for perceived benefits, improved significantly for the participants than for the dropouts. 2 Significant differences in the performance of overall health behaviors and exercise-related behaviors were found between the participants and the dropouts. 3 The sickness impact profile (SIP) of the participants improved significantly, compared with the dropouts. Significant group differences were found for total SIP, physical dimensions, and enjoyment of recreation and pastimes. In conclusion, the study found that the 6-month motivation enhancement program was effective in motivating older adults to perform health behaviors and to improve their functional status.


Identification of novel immunogenic proteins of Shigella flexneri 2a by proteomic methodologies.
Shigella spp. are one of the most important etiological factors for people who are living in developing countries and travelers to tropical countries. High priority has been given by the World Health Organization to the development of vaccines to control Shigellosis caused by these bacteria. However, information regarding to profile of immunogenic proteins of Shigella is not available now. In the present study, sub-immunoproteomics was applied to screen novel immunogenic proteins which could be reacted with antisera produced by challenge of a whole bacterium. Our results indicated that 13 immunogens were identified, in which seven proteins and six proteins from outer membrane and soluble proteome, respectively. Of the 13 proteins, 12 showed to be novel immunogens. These results suggest that immunoproteomics can greatly improve the chances of identification and result in discovery of novel immunogenic proteins.


Poultry immunogenetics: which way do we go?
A major goal in poultry immunogenetics is the enhancement of innate immunoresponsiveness and resistance to disease. This may be pursued by studying either single genes or polygenic traits. The MHC is perhaps the best-characterized family of host genes that modulates response to a variety of antigens and pathogenic challenges. The association of different MHC alleles with disease resistance has been known for decades. But only recently has analysis at the DNA level opened new avenues of understanding and new opportunities for application of genetic variation in the MHC with immunoresponsiveness. An alternate approach to molecular analysis is selection for a desired phenotype controlled by polygenes. Several studies have illustrated the successful alteration of immunoresponsiveness by genetic selection for antibody production. Recently, a selection program based upon multiple traits of immune response was conducted. Results of this project demonstrated that selection on multiple immune-response traits altered immunophysiology, MHC allelic frequencies, and disease resistance. Several areas for future pursuits in poultry immunogenetics research are proposed.


Developmental origins of diabetes-an Indian perspective.
The developmental origins of health disease (DOHaD) hypothesis proposes that altered environmental influences (nutrition, metabolism, pollutants, stress and so on) during critical stages of fetal growth predisposes individuals to diabetes and other non-communicable disease in later life. This phenomenon is thought to reflect permanent effects ('programming') of unbalanced fetal development on physiological systems. Intrauterine programming may underlie the characteristic Indian 'thin-fat' phenotype and the current unprecedented epidemic of diabetes on the backdrop of multigenerational maternal undernutrition in the country. India has been at the forefront of the DOHaD research for over two decades. Both retrospective and prospective birth cohorts in India provide evidence for the role of impaired early-life nutrition on the later diabetes risk. These studies show that in a transitioning country such as India, maternal undernutrition (of micronutrients) and overnutrition (gestational diabetes) co-exist, and expose the offspring to disease risk through multiple pathways. Currently, the Indian scientists are embarking on complex mechanistic and intervention studies to find solutions for the diabetes susceptibility of this population. However, a few unresolved issues in this context warrant continued research and a cautious approach.


Therapeutic drug repositioning with special emphasis on neurodegenerative diseases: Threats and issues.
Drug repositioning or repurposing is the process of discovering leading-edge indications for authorized or declined/abandoned molecules for use in different diseases. This approach revitalizes the traditional drug discovery method by revealing new therapeutic applications for existing drugs. There are numerous studies available that highlight the triumph of several drugs as repurposed therapeutics. For example, sildenafil to aspirin, thalidomide to adalimumab, and so on. Millions of people worldwide are affected by neurodegenerative diseases. According to a 2021 report, the Alzheimer's disease Association estimates that 6.2 million Americans are detected with Alzheimer's disease. By 2030, approximately 1.2 million people in the United States possibly acquire Parkinson's disease. Drugs that act on a single molecular target benefit people suffering from neurodegenerative diseases. Current pharmacological approaches, on the other hand, are constrained in their capacity to unquestionably alter the course of the disease and provide patients with inadequate and momentary benefits. Drug repositioning-based approaches appear to be very pertinent, expense- and time-reducing strategies for the enhancement of medicinal opportunities for such diseases in the current era. Kinase inhibitors, for example, which were developed for various oncology indications, demonstrated significant neuroprotective effects in neurodegenerative diseases. This review expounds on the classical and recent examples of drug repositioning at various stages of drug development, with a special focus on neurodegenerative disorders and the aspects of threats and issues viz. the regulatory, scientific, and economic aspects.


Direct Catalytic Asymmetric Reductive Amination of Aliphatic Ketones Utilizing Diphenylmethanamine as Coupling Partner.
The highly efficient direct catalytic reductive amination of ketones with diphenylmethanamine catalyzed by iridium-phosphoramidite complexes is described. As an effective coupling partner, diphenylmethanamine is suitable for a wide range of ketones to provide chiral amines in high yields and enantioselectivity. The chiral monodentate phosphoramidite ligands are tunable and competent to accommodate substrates with different structures.


Amiodarone-induced ultrastructural changes in human eyes.
Ocular observations in a series of 100 patients treated with amiodarone, along with the pathological changes observed in the eye tissues of two patients treated with this drug, are described in this paper. In the latter two patients intracytoplasmic membrane-bound lamellar bodies similar to myelin were observed by electron microscopy not only in the corneal epithelium and fibroblasts, the conjunctiva and the lens, but also in the corneal endothelium, the iris, the ciliary body, the choroid and the retina. It is suggested that patients taking amiodarone in high dosage for long periods have their eyes and retinal function monitored.


Proprioceptive Opsin Functions in Drosophila Larval Locomotion.
Animals rely on mechanosensory feedback from proprioceptors to control locomotory body movements. Unexpectedly, we found that this movement control requires visual opsins. Disrupting the Drosophila opsins NINAE or Rh6 impaired larval locomotion and body contractions, independently of light and vision. Opsins were detected in chordotonal proprioceptors along the larval body, localizing to their ciliated dendrites. Loss of opsins impaired mechanically evoked proprioceptor spiking and cilium ultrastructure. Without NINAE or Rh6, NOMPC mechanotransduction channels leaked from proprioceptor cilia and ciliary Inactive (Iav) channels partly disappeared. Locomotion is shown to require opsins in proprioceptors, and the receptors are found to express the opsin gene Rh7, in addition to ninaE and Rh6. Besides implicating opsins in movement control, this documents roles of non-ciliary, rhabdomeric opsins in cilium organization, providing a model for a key transition in opsin evolution and suggesting that structural roles of rhabdomeric opsins preceded their use for light detection.


Polymorphisms and haplotypes in the cytochrome P450 17A1, prolactin, and catechol-O-methyltransferase genes and non-Hodgkin lymphoma risk.
Expression of prolactin and of prolactin and estrogen receptors in lymphocytes, bone marrow, and lymphoma cell lines suggests that hormonal modulation may influence lymphoma risk. Prolactin and estrogen promote the proliferation and survival of B cells, factors that may increase non-Hodgkin lymphoma risk, and effects of estrogen may be modified by catechol-O-methyltransferase (COMT), an enzyme that alters estrogenic activity. Cytochrome P450 17A1 (CYP17A1), a key enzyme in estrogen biosynthesis, has been associated with increased cancer risk and may affect lymphoma susceptibility. We studied the polymorphisms prolactin (PRL) -1149G>T, CYP17A1 -34T>C, and COMT 108/158Val>Met, and predicted haplotypes among a subset of participants (n = 308 cases, n = 684 controls) in a San Francisco Bay Area population-based non-Hodgkin lymphoma study (n = 1,593 cases, n = 2,515 controls) conducted from 1988 to 1995. Oral contraceptive and other hormone use also was analyzed. Odds ratios (OR) for non-Hodgkin lymphoma and follicular lymphoma were reduced for carriers of the PRL -1149TT genotype [OR, 0.64; 95% confidence interval (95% CI), 0.41-1.0; OR, 0.53; 95% CI, 0.26-1.0, respectively]. Diffuse large-cell lymphoma risk was increased for those with CYP17A1 polymorphisms including CYP17A1 -34CC (OR, 2.0; 95% CI, 1.1-3.5). ORs for all non-Hodgkin lymphoma and follicular lymphoma among women were decreased for COMT IVS1 701A>G [rs737865; variant allele: OR, 0.53; 95% CI, 0.34-0.82; OR, 0.42; 95% CI, 0.23-0.78, respectively]. Compared with never users of oral contraceptives, a 35% reduced risk was observed among oral contraceptive users in the total population. Reduced ORs for all non-Hodgkin lymphoma were observed with use of exogenous estrogens among genotyped women although 95% CIs included unity. These results suggest that PRL, CYP17A1, and COMT may be relevant genetic loci for non-Hodgkin lymphoma and indicate a possible role for prolactin and estrogen in lymphoma pathogenesis.


PKDL and other dermal lesions in HIV co-infected patients with Leishmaniasis: review of clinical presentation in relation to immune responses.
Co-infection of leishmaniasis and HIV is increasingly reported. The clinical presentation of leishmaniasis is determined by the host immune response to the parasite; as a consequence, this presentation will be influenced by HIV-induced immunosuppression. As leishmaniasis commonly affects the skin, increasing immunosuppression changes the clinical presentation, such as in post-kala-azar dermal leishmaniasis (PKDL) and cutaneous leishmaniasis (CL); dermal lesions are also commonly reported in visceral leishmaniasis (VL) and HIV co-infection. We reviewed the literature with regard to dermal manifestations in leishmaniasis and HIV co-infection, in three clinical syndromes, according to the primary presentation: PKDL, VL, or CL. A wide variety of descriptions of dermal leishmaniasis in HIV co-infection has been reported. Lesions are commonly described as florid, symmetrical, non-ulcerating, nodular lesions with atypical distribution and numerous parasites. Pre-existing, unrelated dermal lesions may become parasitized. Parasites lose their tropism and no longer exclusively cause VL or CL. PKDL in HIV co-infected patients is more common and more severe and is not restricted to Leishmania donovani. In VL, dermal lesions occur in up to 18% of patients and may present as (severe) localized cutaneous leishmaniasis, disseminated cutaneous leishmaniasis (DL) or diffuse cutaneous leishmaniasis (DCL); there may be an overlap with para-kala-azar dermal leishmaniasis. In CL, dissemination in the skin may occur resembling DL or DCL; subsequent spread to the viscera may follow. Mucosal lesions are commonly found in VL or CL and HIV co-infection. Classical mucocutaneous leishmaniasis is more severe. Immune reconstitution disease (IRD) is uncommon in HIV co-infected patients with leishmaniasis on antiretroviral treatment (ART). With increasing immunosuppression, the clinical syndromes of CL, VL, and PKDL become more severe and may overlap. These syndromes may be best described as VL with disseminated cutaneous lesions (before, during, or after VL) and disseminated cutaneous leishmaniasis with or without visceralization.


A randomized controlled trial of lamivudine to treat acute hepatitis B.
The role of antivirals in patients with acute viral hepatitis B (AVH-B) has not been evaluated in controlled trials. The aim of this study was to evaluate the efficacy of lamivudine in patients with AVH-B. AVH-B patients with serum bilirubin of more than 5 mg/dL were randomized to receive either 100 mg of lamivudine daily for 3 months (group 1, n = 31) or placebo (group 2, n = 40). Patients were considered to have severe AVH-B if they fulfilled 2 of 3 criteria: (1) hepatic encephalopathy; (2) serum bilirubin > or = 10.0 mg/dL; and (3) international normalized ratio (INR) > or = 1.6. At week 4, HBV DNA levels were significantly lower (P = 0.037) in group 1 (median: 3.6721 log copies/mL) than group 2 (median: 4.2721 log copies/mL). Thereafter, HBV DNA levels were comparable in the 2 groups. The improvement in serum bilirubin, ALT, and INR values was similar in the 2 groups. Twenty-two patients (71%) in group 1 and 25 patients (62.5%) in group 2 had severe AVH-B. Results were similar when patients with severe AVH-B were analyzed separately. After 12 and 18 months, 93.5% and 92.5%, respectively, of patients in the lamivudine group and 96.7% and 97.5%, respectively, of patients in the placebo group lost HBsAg. There were no deaths in either group. After 1 year, 21 patients (67.7%) in group 1 and 34 patients (85%) in group 2 developed protective anti-HBs titers (P = 0.096). All HBeAg-positive patients in both groups lost e antigen and anti-HBe developed in 71% and 87.5% of patients in groups 1 and 2, respectively (P = 0.132). Though lamivudine causes a greater decrease in levels of HBV DNA, it does not cause significantly greater biochemical and clinical improvement as compared to placebo in patients with acute hepatitis B.


SNP ID-info: SNP ID searching and visualization platform.
Many association studies provide the relationship between single nucleotide polymorphisms (SNPs), diseases and cancers, without giving a SNP ID, however. Here, we developed the SNP ID-info freeware to provide the SNP IDs within inputting genetic and physical information of genomes. The program provides an "SNP-ePCR" function to generate the full-sequence using primers and template inputs. In "SNPosition," sequence from SNP-ePCR or direct input is fed to match the SNP IDs from SNP fasta-sequence. In "SNP search" and "SNP fasta" function, information of SNPs within the cytogenetic band, contig position, and keyword input are acceptable. Finally, the SNP ID neighboring environment for inputs is completely visualized in the order of contig position and marked with SNP and flanking hits. The SNP identification problems inherent in NCBI SNP BLAST are also avoided. In conclusion, the SNP ID-info provides a visualized SNP ID environment for multiple inputs and assists systematic SNP association studies. The server and user manual are available at http://bio.kuas.edu.tw/snpid-info.


Conservative treatment using laser diode and systemic chemotherapy for early-stage bilateral retinoblastoma: A 14-year prospective cohort study.
Solid evidence of the safety and effectiveness of retinoblastoma (RB) conservative treatment using thermotherapy and systemic chemotherapy with long-term follow-up is scarce, especially in low-resource countries. This study examined the outcomes of this treatment and associated predictors in Vietnam to strengthen the current RB treatment protocol focusing on preserving eye and vision in low-resource settings. A prospective cohort study was conducted at Ho Chi Minh City Eye Hospital in Vietnam from 2005 to 2019. All eligible patients with bilateral RB (one eye already removed and another eye classified as group A or B) and without previous treatment were recruited. All patients received thermotherapy and six cycles of systemic three-agent chemotherapy repeated every 4 weeks. A standardized questionnaire was used to collect information on study participants' age, symptoms, tumor characteristics, treatment, and outcomes. Among 50 eyes of all 50 patients with a median age of 9 (4-20) months, 34 eyes were in group B (68%). The median follow-up time was 60 (60-84) months. All 139 preserved tumors regressed mostly to type 4 (70.4%) and type 3 (23.7%) scars. Kaplan-Meier analysis found the overall globe-salvage rate at 5 years of 91.9% (95% CI: 80.1%-97.7%). Most eyes (41/50, 82%, 95% CI: 69.2%-90.2%) had a final visual acuity ≥0.1. The visual acuity is higher when tumors regressed to a type 4 scar (p = .007, AOR = 8.098, 95% CI: 1.79-36.53) which also shows less enucleation than a type 3 scar (p = .002, AOR = 0.06, 95% CI: 0.01-0.37%). Gender effect on visual acuity after treatment was significant and may be due to discrimination. No major complications were recorded. Conservative treatment of early-stage RB is safe and effective. Long-term, thorough follow-ups of patients post-treatment are needed. The regression patterns of scars could be a useful indicator of treatment failure.


Gastric emptying rate measurement in man. A double isotope scanning technique for simultaneous study of liquid and solid components of a meal.
A sequential scintiscanning method was used to study gastric emptying in a total of 46 patients given a meal of cornflakes, sugar and milk containing radioactive markers of the solid and liquid components. In control and duodenal ulcer patients, liquid emptying was faster than solid emptying and could be represented as a monoexponential process, but solid emptying followed a different pattern, better represented as linear emptying with time. However, in patients who had undergone Billroth II gastrectomy there was no evidence of differential emptying of the two markers. In addition, rapid emptying of both markers occurred in the gastrectomy patients during the first 10 min after meal ingestion but did not occur in control or duodenal ulcer patients. The observations illustrate the limitations of using liquid meals to identify the effects of gastric surgery on emptying. Measurements of early emptying and of solid-liquid differentiation are necessary for full definition of gastric emptying after ingestion of a mixed solid and liquid meal.


Does entry test make any difference on the future performance of medical students?
To observe the influence/efficiency of entry test in the selection of students for MBBS. To see the effect of FSC and Entry test marks on the future performance of students in the coming years. This was an Analytical Prospective Longitudinal study carried out in a private medical college from December 2009 to April 2011. Sampling was universal as all the students of year 2009 who succeeded in getting admission were included. The subjects were selected at the time of admission and the whole class (admission intake) comprising of 100 students during the admission year 2009 were studied. The same cohort was observed over a period of three years. The base line data was collected from the record, documents submitted at the time of admission and verified from the original record. The results of FSC and entry test are consistent in approximately all the percentage groups who got above 70% marks in FSC. Consistency was only disturbed in students who acquired 61-70% marks in FSC and entry test. The students who got 81-90% in FSC and Entry test performed well in first and second year MBBS. The males who had 66-70% marks in FSC were the poor performers (100% failed 5 out of 5) while among the females (33% failed) who got 71-75% in FSC. Best performance was shown by those who got 81-85% in FSC i.e. 91% males and 90% females passed in annual examinations. The results of FSC and Entry test are highly significant in statistical application and hence there was no association between the entry test marks and future performance. FSC marks are of prime importance, and are the best marker for merit admission in medical college. Entry test is the tool for equalization in between different institutions, boards and provinces. It controls the errors and omissions done deliberately or unintentionally by students, board mal-practitioners and other confounders at institution and board level in FSC.


Mechanical receptor-related mechanisms in scar management: a review and hypothesis.
The physiopathogenesis of proliferative scarring in human skin is not well understood. Furthermore, knowledge of the precise mechanisms of action for physical treatment modalities is limited. Compression garments, occlusive/adhesive skin taping, and silicone gel sheets are applied to form an occlusion on the scar surface, reduce tension, and/or increase pressure on the scar itself. The mechanisms by which the external or superficial actions of these treatments cause remission of a protruding scar may be related to mechanoreceptor (nociceptor and cellular mechanoreceptor) responses. Basic research studies about mechanoreceptor-related (nociceptors and cellular mechanoreceptors, separately) events are reviewed and discussed based on proliferative scarring background. Scar management-related studies were corrected from the standpoint of mechanotransduction mechanisms. The methodologic quality of the clinical trials and basic studies was evaluated and reviewed. It was suggested that many of the physical scar management methods, including compression therapy, silicone therapy, adhesive tape, and occlusive dressing therapy, are related to mechanotransduction mechanisms. A unifying perspective of basic research findings and clinical observations may be obtained by considering the mechanoreceptor-related events in scar management. Moreover, a precise understanding of the roles that cellular mechanoreceptors and mechanosensitive nociceptors play in proliferative scarring may lead to the development of innovative treatment strategies and new pharmacologic therapies targeting cellular mechanoreceptors and mechanosensitive nociceptors in fibroproliferative diseases.


The treatment of lower pole renal calculi in 2003.
The optimal treatment of patients with lower pole renal calculi is still being defined. Shock wave lithotripsy, percutaneous nephrolithotomy, and ureteroscopy are all currently utilized to treat patients with this condition. These methods have yielded varying degrees of success. The influence of collecting system anatomy on shock wave lithotripsy results remains controversial. Ongoing randomized, prospective trials evaluating the efficacy of all of these respective therapeutic options will, it is hoped, determine the best approaches for this patient cohort.


Metabolomics Insights into the Modulatory Effects of Long-Term Low Calorie Intake in Mice.
There is increasing evidence that calorie restriction without malnutrition can extend longevity and delay the onset of age-associated disorders. Identifying the biochemical perturbations associated with different dietary habits would provide valuable insights into associations between metabolism and longevity. To reveal the effects of long-term dietary interventions on metabolic perturbations, we investigated serum and urinary metabolic changes induced by interactive high/low fat diet in combination with/without reduced caloric intake over a life span in mice using NMR-based metabonomics. We found that the high calorie dietary regime disturbed lipid metabolism, suppressed glycolysis and TCA cycles, stimulated oxidative stress, promoted nucleotide metabolism and gluconeogenesis, and perturbed gut microbiota-host interactions. Such changes could be modified by long-term low calorie intake. Most importantly, we found that the calorie intake index exerts a dominant effect on metabolic perturbations irrespective of dietary regime. Our investigation provides a holistic view of the metabolic impact of long-term dietary interventions, which are important for detecting physiological changes and dietary effects on mammalian metabolism.


Production of nucleic acid-related substances by fermentative processes. XIX. Accumulation of 5'-inosinic acid by a mutant of Brevibacterium ammoniagenes.
The accumulation of 5'-inosinic acid (IMP) by a mutant, KY 13102, induced from Brevibacterium ammoniagenes ATCC 6872 by ultraviolet light irradiation, was examined. Although growth was stimulated by adenine or adenosine, the microorganism showed fair growth in the medium containing amino acids but no adenine. Among six kinds of natural nutrients tested, meat extract and Casamino Acids were suitable for the accumulation of IMP. Manganese ion strongly affected growth, the accumulation of IMP and hypoxanthine, and cell morphology. Among amino acids tested, L-methionine, L-proline, and L-valine stimulated IMP accumulation. In the medium containing 1.0 g of L-proline per liter, 12.8 mg of IMP per ml was accumulated. The mechanism of IMP accumulation by the mutant is discussed.


Evolution of Climatic Related Leaf Traits in the Family Nothofagaceae.
The current relationship between leaf traits and environmental variables has been widely used as a proxy for climate estimates. However, it has been observed that the phylogenetic relationships between taxa also influence the evolution of climatic related leaf traits, implying that the direct use of the physiognomy-climate relation should be corrected by their ancestor-descendant relations. Here, we analyze the variation of 20 leaf traits during the evolution of 27 species in the Gondwana family Nothofagaceae. We evaluate whether the evolution of these traits is exclusively associated with past climate variations or whether they are restricted by phylogenetic relationships. Our results indicate that four leaf traits, associated with size and shape, had consistently a phylogenetic independent evolution, suggesting adaptive variation with the environment. While three of the traits, presented consistently phylogenetic signal and fit a Brownian motion or Ornstein-Uhlenbeck model of evolution, suggesting that the evolution of these traits is restrained by phylogenetic relationships and implying that phylogenetic corrections should be made for the family Nothofagaceae to use them as climatic proxy. Finally, this study highlights the importance of evaluating the evolutionary history of climatic related leaf traits before conducting paleoclimate estimates.


Potential link between SARS-CoV-2 and Kawasaki disease: importance of dentists for the diagnosis.
Kawasaki disease (KD) is a vasculitis with predilection for coronary arteries. Due to a lack of reliable confirmatory laboratory tests, the diagnosis of KD is based on a characteristic pattern of clinical findings that appear in a typical temporal sequence. The diagnostic criteria have been periodically modified and the American Heart Association has proposed the most recent guidelines for its diagnosis. However, patients may have incomplete or atypical forms of KD and diagnosis can often be difficult. Because oropharyngeal manifestations are a common and important feature for diagnosing KD and recent studies have hypothesized a possible association between KD and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in this review we highlight the importance of dentists in the diagnosis of KD and its potential association with SARS-CoV-2.


Anticipating the Ethical Challenges of Psychiatric Genetic Testing.
Genetic testing for mental illness is likely to become increasingly prevalent as the science behind it is refined. This article identifies anticipated ethical challenges for patients, psychiatrists, and genetic counselors and makes recommendations for addressing them. Many of the ethical challenges of psychiatric genetic testing are likely to stem from failures to comprehend the nature and implications of test results. Recent studies have identified gaps in the knowledge base of psychiatrists and genetic counselors, which limit their abilities to provide patients with appropriate education. A small number of studies have demonstrated the value of counseling in empowering patients to deal with relevant genetic information. Psychiatrists and other health professionals must be able to assist patients and families in making informed decisions about genetic testing and interpreting test results. Filling their knowledge gaps on these issues will be a critical step towards meeting these responsibilities.


Identification of Disease-Causing Mutations by Functional Complementation of Patient-Derived Fibroblast Cell Lines.
Diagnosis of mitochondrial disorders is still hampered by their phenotypic and genotypic heterogeneity. In many cases, exome sequencing, the state-of-the-art method for genetically diagnosing mitochondrial disease patients, does not allow direct identification of the disease-associated gene but rather results in a list of variants in candidate genes. Here, we present a method to validate the disease-causing variant based on functional complementation assays. First, cell lines expressing a wild-type cDNA of the candidate genes are generated by lentiviral infection of patient-derived fibroblasts. Next, oxidative phosphorylation is measured by the Seahorse XF analyzer to assess rescue efficiency.


Transcriptome of local innate and adaptive immunity during early phase of infectious bronchitis viral infection.
To understand the mechanistic basis of local innate and adaptive immunity against infectious bronchitis virus (IBV) at the molecular level, we examined the gene transcription profile of tracheal epithelial layers 3 d after infection of chickens with an attenuated IBV-Massachusetts strain. Results suggested that the transcription levels of 365 genes were either upregulated or downregulated (2-fold and higher) after IBV infection. Among the upregulated 250 genes, 25 were directly immune-related genes. These upregulated immune response genes included TLR2, TLR3, interferon-induced antiviral genes (Mx), and genes responsible for cytotoxic T cell killing such as Fas antigen and granzyme-A. Overall, a diversity of innate immunity and helper T cell type 1 (Th1)-biased adaptive immunity are activated in the host's early defense against IBV invasion, and they are responsible for the rapid clearance of virus from the local infection.


Do external stimuli impact the gait of children with idiopathic toe walking? A study protocol for a within-subject randomised control trial.
Frequently, toe walking gait is the result of disease processes, trauma or neurogenic influences. Idiopathic toe walking (ITW) is, by definition, the diagnosis of a toe walking gait adopted in the absence of one of these medical conditions. Long-term ITW has been associated with reduced ankle range of motion. Reported treatments have included serial casting, Botulinum toxin type A or surgery to improve the ankle range of motion. Investigating the impact of simple and non-invasive treatment options for ITW is important for future research and clinical outcomes. This study investigates the immediate impact of footwear, footwear with orthotics and whole body vibration on ITW to determine if any one intervention improves heel contact and spatial-temporal gait measures. This determination is important for future clinical trials into treatment effectiveness. this protocol describes a within-subject randomised controlled trial that measures changes in gait following changes in external stimuli. 15 children diagnosed with an ITW gait will be recruited from the Victorian Paediatric Rehabilitation Service at Monash Children's Hospital Toe Walking Clinic provided they have ITW and meet the inclusion criteria. participants will have their gait recorded walking barefoot, in usual footwear, a custom-made, full-length carbon fibre orthotic in usual footwear and following whole body vibration. Outcome measures will include the presence of bilateral heel contact preintervention and postintervention, stride length (cm), stride width (cm), left and right stride time (s), left and right stance and swing percentage of the gait cycle, gait velocity (m/s), left and right foot toe in/toe out angle (°) and weight-bearing lunge pre and post each condition. The results of this study will be published at the conclusion and have been approved by Southern Health HREC:12102B. ACTRN12612000975897.


Can Only the Shape Feature in Radiomics Help Machine Learning Show That Bladder Cancer Has Invaded Muscles?
The presence of muscle invasion is an important factor in establishing a treatment strategy for bladder cancer (BCa). The aim of this study is to reveal the diagnostic performance of radiomic shape features in predicting muscle-invasive BCa. In this study, 60 patients with histologically proven BCa who underwent a preoperative MRI were retrospectively recruited. The whole tumor volume was segmented on apparent diffusion coefficient (ADC) maps and T2W images. Afterward, the shape features of the volume of interest were extracted using PyRadiomics. Machine learning classification was performed using statistically different shape features in MATLAB® (The MathWorks, Inc., Natick, Massachusetts, United States). The findings revealed that 27 bladder cancer patients had muscle invasion, while 33 had superficial bladder cancer (53 men and seven women; mean age: 62±14). Surface area, volume, and relevant features were significantly greater in the invasive group than in the non-invasive group based on the ADC maps (P<0.05). Superficial bladder cancer had a more spherical form compared to invasive bladder cancer (P=0.05) with both imaging modalities. Flatness and elongation did not differ significantly between groups with either modality (P>0.05). Logistic regression had the highest accuracy of 83.3% (sensitivity 82.8%, specificity 84%) in assessing invasion based on the shape features of ADC maps, while K-nearest neighbors had the highest accuracy of 78.2% (sensitivity 79.1%, specificity 69.4%) in assessing invasion based on T2W images. Shape features can be helpful in predicting muscle invasion in bladder cancer using machine learning methods.


[Association of health literacy and screen time with depressive symptoms among middle school students].
To examine the association of health literacy( HL), screen time and depressive symptoms in middle school students. In December 2017, a convenient cluster sampling method was used to select all the students from Junior 1 to Senior 3 in a middle school in Shenyang City in the cooperation area as the subjects. And 1062 valid questionnaires were collected, with the use of the group's self-made questionnaire. The average age of the 1062 students was( 15. 38 ± 1. 74) years old, among which 576 boys and 486 girls were surveyed. Questionnaires survey was conducted to collect information on demographics, health literacy, screen time of study day and depressive symptoms. The Chi-square test was performed according to group differences, and multiple Logistic regression model was used to analyze the association of health literacy( including three dimensions of interpersonal relationship, stress management and mental growth) and screen time and their different combinations and depressive symptoms. The detection rate of depressive symptoms among middle school students was 26. 1%( 277/1062). The prevalence of depressive symptoms among students in high school students, low family income and longer screen time was significantly higher than their peers( χ~2 were 15. 090, 10. 510, 4. 832, P < 0. 05). Data from multiple logistic regression analyses showed that low health literacy, longer screen time and low mental growth were positively correlated with depressive symptoms in middle school students( P < 0. 05). In the same level of health literacy, with the increase of screen time, the higher the detection rate of depressive symptoms of middle school students, the highest detection rate of depressive symptoms of middle school students with longer screen time and low health literacy was 51. 7%( 30/58), and the OR value was 5. 741( 95% CI 2. 999-10. 999). Health literacy and screen time are related factors of depressive symptoms. The detection rate of depressive symptoms of middle school students with longer screen time and low health literacy is the highest.


Maximizing patient care services to improve funding in a family medicine residency.
The authors discuss ways to increase the funding base of a family medicine residency program through the appropriate use of procedures related to patient care and the provisions of service. Following a commitment of cooperation by residents and faculty members, certain principles of a business practice management curriculum were expanded and applied to a residency program. A written procedure manual describing the intricacies of the fee-for-service system was prepared for interns. Mechanisms for the review of patient care productivity and educationally productive incentives were developed. All of these steps were helpful in achieving improvement in the funding base for the residency. Areas for potential expansion in training programs and financial and staffing strategies to increase revenues are discussed. Although administrative decisions regarding fees and collection mechanisms are mentioned, this discussion focuses on educational and patient care activities that also produce revenue.


Aptamer-mediated magnetic and gold-coated magnetic nanoparticles as detection assay for prion protein assessment.
This article reports the chemical synthesis and functionalization of magnetic and gold-coated magnetic nanoparticles. The binding characteristics of streptavidin-conjugated nanoparticles were studied using prion protein as a target to a specific biotinylated aptamer. The size and structure of the particles were determined by transmission electron microscopy, and the binding of the prion to the particle was confirmed by Fourier transform infrared spectroscopy. The rate of prion binding to the aptamer was dose-dependent, and prion immobilization was more effective on L-aspartic acid-functionalized magnetic nanoparticles compared to the carboxyl-functionalized gold-coated magnetic nanoparticles. This study sets the stage for the development of prion detection platforms as well as our long-term goals in structure elucidation at the binding interface.


Pyrazinoindole-Based Lewis-Acid/Base Assembly: Intriguing Intramolecular Charge-Transfer Switching through the Dual-Sensing of Fluoride and Acid.
Pyrazinoindole-based Lewis-acid/base assemblies are prepared through the use of regioselective formal [3 + 3] cycloaddition reactions, and their intriguing photophysical properties are described. The assemblies exhibit strong emissions in THF solution, which are attributed to through-space intramolecular charge-transfer (ICT) transitions between the branched Lewis-acid/base moieties. Furthermore, these show ratiometric color-change responses in PL titration experiments, which give rise to new colors through turn-on emissions ascribable to ICT transitions that alternate between the pyrazinoindole units and each triarylboryl or amino moiety, a consequence of the binding of the fluoride or acid. Pieces of filter paper covered by these assemblies exhibited blue-shifted color changes when immersed in aqueous acidic solutions, suggesting that these are promising candidate indicators that detect acid through emissive color. Computational data for these assemblies and their corresponding adducts verify the existence of ICT transitions that alternate through fluoride or acid binding.