Biosynthesis and identification of volatiles released by the myxobacterium Stigmatella aurantiaca.
The volatiles released by agar plate cultures of two strains of the myxobacterium Stigmatella aurantiaca (strains Sg a15 and DW4/3-1) were collected in a closed-loop stripping apparatus (CLSA) and analyzed by GC-MS. Large numbers of substances from different compound classes (ketones, esters, lactones, terpenes, and sulfur and nitrogen compounds) were identified; several of them are reported from natural sources for the first time. The volatiles 2-methyltridecan-4-one (17), its isomer 3-methyltridecan-4-one (20), and the higher homologue 2-methyltetradecan-4-one (18) were identified in the extracts of both strains and were synthesized. In addition, strain Sg a15 produced 2,12-dimethyltridecan-4-one (19), 2-methyltridec-2-en-4-one (23), and a series of phenyl ketones, among them 1-phenyldecan-1-one (14) and 9-methyl-1-phenyldecan-1-one (16), whereas strain DW4/3-1 emitted traces of 10-methylundecan-2-one (21). The biosynthesis of 14 and 16 was examined in feeding experiments with deuterated precursors carried out on agar plate cultures. The leucine-derived starter unit isovalerate was shown to be incorporated into 16, as was phenylalanine-derived benzoic acid into both 14 and 16. The results point to formation both of the phenyl ketones and of the structurally related aliphatic ketones through an unusual head-to-head coupling between a starter unit such as benzoyl-CoA and a fatty acyl-CoA, followed by decarboxylation.


The evolution of geriatric neurology.
The founders of neurology in the late 19th century and early 20th century laid the foundation for modern geriatric neurology by detailed observations, in their patients, of the clinical expressions of aging of the nervous system. Further advances in clinical manifestations of aging and more detailed examination of disease states in the elderly accelerated in the last quarter of the 20th century. Basic, translational, and clinical research support of geriatric neurology studies expanded and advanced during this period and into the 21st century. The size and sophistication of this movement was stimulated by a number of factors: the successful development of geriatrics as a specialty in primary care, internal medicine, and psychiatry; the projected growth of the geriatric population; and the projections of the number of people with Alzheimer's disease. However, there were and continue to be inadequate numbers of trained geriatric neurologists available to care for the "silver tsunami" of elderly patients with age-related diseases that will present in the next 3 decades. The combination of massive investment in dementia/Alzheimer's research in the past decade, widespread awareness among researchers and trainees of the opportunities to do research in age-related diseases, and the need for further knowledge of neurodegenerative diseases led to a broad expansion of research efforts. Longitudinal clinical studies of the elderly and the advent of sophisticated neuroimaging, genetics, and laboratory techniques are advancing the field. The initiation of therapeutic interventions has led to cautious optimism about the ability to ameliorate suffering in these patients and diminish the burdens of central nervous system aging.


Transmissible ER stress reconfigures the AML bone marrow compartment.
Successive adaptation of the bone marrow (BM) from homeostatic hematopoietic microenvironment to a self-reinforcing niche is an integral aspect of leukemogenesis. Yet, the cellular mechanisms underlying these functional alterations remain to be defined. Here, we found that AML incursion precipitates compartmental endoplasmic reticulum (ER) stress and an unfolded protein response (UPR) in both leukemia and stromal cells. We observed that extracellular vesicles (EV) transmit ER stress in vivo from the AML xenograft to BM stroma, whereby the upregulation of core UPR components drives subsequent osteolineage differentiation of mesenchymal stem cells (MSC). Finally, we show that the underlying mechanism involves quantitative incorporation and cell-cell transfer of Bone Morphogenic Protein 2 (BMP2), a potent osteogenic signal, by AML-EVs. Corroborative studies in AML patient samples support the translational relevance of AML-EVs as a platform for BMP trafficking and source of compartmental crosstalk. Transmissible ER stress was previously identified as a source of chemoresistance in solid tumor models, and this work reveals a role in remodeling the BM niche in AML.


Clinical and Functional Characterization of Pre-frailty among Elderly Patients Consulting Primary Care Centres.
Characterization of the main features of pre-frailty may contribute to better understanding the mechanisms involved in the development of frailty. To characterize the pre-frail population consulting in primary care centres in Mataró (Catalonia, Spain), to describe the Fried's frailty criteria for this population and to identify the main associated factors. Cross-sectional study. Three primary care centres in Catalonia. Pre-frail subjects recruited from among persons aged 70 years and older consulting primary care centres and screened for frailty according to Fried's criteria. Clinical, nutritional and functional data. Frailty prevalence of 31.0% and pre-frailty prevalence of 49.0% were observed. Comorbidity was not especially frequent among elderly individuals classified as pre-frail (except for diabetes with 35.8% prevalence). Functional status and nutritional status were both reasonably satisfactory in pre-frail subjects with mean Barthel score of 98 points and 91% classified as well nourished. Among pre-frail subjects, 35% were obese (body mass index>30); 75% reported pain; 12% had an accidental fall in the previous three months; and the mean number of medications ingested was 6.2. Weakness was the most prevalent frailty criterion (70%), followed by slowness (30%). Weakness was associated with age in men and with pain in women. Poor physical activity was associated with pain. Pre-frailty is very common among elderly subjects consulting primary care centres. Weakness, slowness, diabetes, pain and polypharmacy should alert healthcare professionals to the onset of a frailty process.


Protein/creatinine ratio in the assessment of proteinuria during pregnancy.
Since the nature and the level of urinary protein excretion have considerable clinical implications in the course of pregnancy, the early detection of even minor degrees of hyperproteinuria is important. Quantitation of 24-h urinary protein excretion is the only definite method of establishing the presence of hyperproteinuria, but this method shows practical failures particularly in an outpatient setting. Dipstick analysis as a screening for hyperproteinuria also lacks reliability, since the normal rate of protein excretion in primigravid pregnancy has recently been shown to be less that 150 mg per day. In this study, therefore, we propose the determination of the protein/creatinine ratio in a single voided urine sample, obtained during normal daylight activity, as a screening test for hyperproteinuria during pregnancy which can replace the quantitation of 24-h urinary protein excretion.


Nipah virus: A review on epidemiological characteristics and outbreaks to inform public health decision making.
The objectives of this review were to understand the epidemiology and outbreak of NiV infection and to discuss the preventive and control measures across different regions. We searched PubMed and Scopus for relevant articles from January 1999 to July 2018 and identified 927 articles which were screened for titles, abstracts and full texts by two review authors independently. The screening process resulted in 44 articles which were used to extract relevant information. Information on epidemiology of NiV, outbreaks in Malaysia, Singapore, Bangladesh, India and Philippines, including diagnosis, prevention, treatment, vaccines, control, surveillance and economic burden due to NiV were discussed. Interdisciplinary and multi sectoral approach is vital in preventing the emergence of NiV. It is necessary to undertake rigorous research for developing vaccines and medicines to prevent and treat NiV.


A methionine-reversible folate deficiency in rats following the acute administration of diethylnitrosamine and alpha-naphthylisothiocyanate.
Acute doses of the hepatotoxic agents diethylnitrosamine (DEN) and alpha-naphthylisothiocyanate (ANIT) to young adult male rats led to the production of a folate deficiency as determined by an elevated urinary excretion of formiminoglutamic acid (FIGLU) 2 to 4 days following administration of the compounds. High dietary levels of methionine significantly reduced the elevated levels of FIGLU produced by the 2 chemicals. Dietary folate had no significant effect on the excretion of urinary FIGLU. Although the hepatic levels of S-adenosylmethionine (SAM) were significantly increased in rats fed the high dietary levels of methionine, an acute dose of DEN did not depress the hepatic levels of SAM. The results indicate that the methyl-reversible folate deficiency caused by hepatotoxic agents is not the direct consequence of altered hepatic levels of SAM.


The formation of hydroxyproline in collagen by cells grown in the absence of serum.
L-929 and 3T6 cells were conditioned to grow in a chemically defined medium lacking serum and ascorbate. Serum, when added, had a small stimulatory effect on the growth rate of the cells, but ascorbate had no effect either on the growth rate or on the rate of protein synthesis. These cells were also shown to lack gulonolactone oxidase activity and therefore could not synthesize their own ascorbate. Nevertheless, in the absence of serum and ascorbate both cell types were able to hydroxylate peptidyl proline to an appreciable extent. This suggests that reductants other than ascorbate can at least partially satisfy the requirement for a reductant in the prolyl hydroxylase reaction in vivo.


Hodgkin Lymphoma and Its Differential Diagnosis: New Twists on an Old Challenge.
Hodgkin lymphoma is a B-cell neoplasm that typically presents with localized, nodal disease. Tissues are characterized by few large neoplastic cells, usually comprising less than 10% of tissue cellularity, present in a background of abundant nonneoplastic inflammatory cells. This inflammatory microenvironment, although key to the pathogenesis, can make diagnosis a challenge because reactive conditions, lymphoproliferative diseases, and other lymphoid neoplasms may mimic Hodgkin lymphoma and vice versa. This review provides an overview of the classification of Hodgkin lymphoma, its differential diagnosis, including emerging and recently recognized entities, and strategies to resolve challenging dilemmas and avoid diagnostic pitfalls.


Exogenous priming of chitosan induces upregulation of phytohormones and resistance against cucumber powdery mildew disease is correlated with localized biosynthesis of defense enzymes.
In recent years, exploration of biopolymer-based materials to avoid hazardous chemicals in agriculture has gained enormous importance for sustainable crop improvement. In the present study, chitosan a biopolymer derived from crab-shell was used in different concentrations as priming agent to cucumber seeds and were evaluated for its effect to enhance plant growth parameters as well as its ability to induce resistance against powdery mildew disease. Among the treatments, seeds-primed with 2.5 mg/mL exhibited early seedling germination of 90% and vigour of 2665 and also remarkably enhanced the cucumber growth parameters which might be fairly attributed to the stimulation of phytohormones content in primed plants over the controls. More importantly, under greenhouse conditions a significant induced disease protection of 66.6% against powdery mildew disease was noticed in chitosan-pretreated plants at 2.5 mg/mL. The induced resistant plants also showed a significant deposition of lignin, callose and H2O2. Notably, polyphenol oxidase, phenylalanine ammonia-lyase, peroxidase and glucanase defense-responsive enzymes were upregulated in chitosan-primed plants. Considered together, these results determine that the susceptible cucumber cultivar elicits immunity after perception of priming with chitosan to upregulate phytohormones and synthesize defense-responsive enzymes, thereby induce resistance against powdery mildew disease and strengthen the growth-promotion of cucumber plants.


Perspectives on radiation dose in abdominal imaging.
Reported instances of patients' overexposure to imaging-related radiation have spurred the radiology and medical physics communities to identify and develop methods for decreasing the amount of radiation used to achieve diagnostic-quality images. These initiatives include examining and optimizing conventional CT scanning parameters, introducing innovative scan protocols, and incorporating novel dose reduction technologies. The greatest challenge to effective dose reduction in the abdomen and pelvis remains patient size. Here, we review the state of the art in abdominopelvic CT in both adult and pediatric patients and describe some of our own efforts in dose reduction for these types of examinations.


Correlation between susceptibility to chloramphenicol, tetracycline and clindamycin, and serogroups of Clostridium difficile.
A total of 114 Clostridium difficile strains were analysed for a possible correlation between serological susceptibility to chloramphenicol, tetracycline and clindamycin, and serogrouping. All 17 chloramphenicol-resistant strains belonged to serovar I, while none of 32 tetracycline-resistant strains belonged to serovar I. All strains included in serovar III were tetracycline- and clindamycin-resistant.


Immunogenicity and Reactogenicity of Messenger RNA Coronavirus Disease 2019 Vaccine Booster Administered by Intradermal or Intramuscular Route in Thai Older Adults.
Intradermal (ID) vaccination may alleviate COVID-19 vaccine shortages and vaccine hesitancy. Persons aged ≥65 years who were vaccinated with 2-dose ChAdOx1 12-24 weeks earlier were randomized to receive a booster vaccination by either ID (20 µg mRNA-1273 or 10 µg BNT162b2) or intramuscular (IM) (100 µg mRNA-1273 or 30 µg BNT162b2) route. Anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibody (NAb), and interferon gamma (IFN-γ)-producing cells were measured at 2-4 weeks following vaccination. Of 210 participants enrolled, 70.5% were female and median age was 77.5 (interquartile range, 71-84) years. Following booster dose, both ID vaccinations induced 37% lower levels of anti-RBD IgG compared with IM vaccination of the same vaccine. NAb titers against ancestral and Omicron BA.1 were highest following IM mRNA-1273 (geometric mean, 1718 and 617), followed by ID mRNA-1273 (1212 and 318), IM BNT162b2 (713 and 230), and ID BNT162b2 (587 and 148), respectively. Spike-specific IFN-γ responses were similar or higher in the ID groups compared with IM groups. ID route tended to have fewer systemic adverse events (AEs), although more local AEs were reported in the ID mRNA-1273 group. Fractional ID vaccination induced lower humoral but comparable cellular immunity compared to IM and may be an alternative for older people. TCTR20220112002.


Reduced Narcotic Utilization in Total Joint Arthroplasty Patients in an Urban Tertiary Care Center.
Opioid use after total joint arthroplasty must be balanced against the risks of opioid dependence and diversion. This study sought to define the baseline patient characteristics and discharge opioid use after the initiation of a preoperative and postoperative institutional opioid prescription protocol in a population with a high prevalence of opioid dependence and substance use. Data on 1004 patients undergoing total joint arthroplasties from July 1, 2017, to June 30, 2019, were retrospectively reviewed. Demographics were collected, and data were grouped into high- and low-discharge opioid groups based on 1 standard deviation above or below the mean. Patient characteristics of the high and low groups were compared using one-way analysis of variance and Pearson chi-square test. The prevalence of preoperative opioid dependence was 21.8%. The mean discharge opioid prescription was 264 morphine milligram equivalents (MMEs). The cutoffs of high- and low-use groups were above 424 MMEs and below 104.5 MMEs. The high-discharge opioid group was more likely to be male, younger, to have a history of preoperative opioid use, to undergo general anesthesia, and to be uninsured. The lower-discharge opioid group was more likely to be older, female, to have Medicare, and to stay approximately 1 day longer in the hospital. Body mass index, intraoperative opioid requirement, American Society of Anesthesiologists Classification score, race, total knee vs total hip arthroplasty, or surgical approach for total hip arthroplasty did not affect discharge opioid prescriptions. Reduction of opioid prescriptions at discharge in total joint arthroplasty patients may be possible with the use of preoperative and postoperative protocols, optimizing patient risk factors for opioid use and utilizing a patient-specific opioid taper regimen.


The role of the secretory immunological synapse in killing by CD8+ CTL.
Immunological synapses are formed between several different pairs of effector and target cells in the immune system and are thought to be important for sustaining signalling events in the effector cell. Although the interaction between CD8(+) lymphocytes and the targets that they kill is short lived, nevertheless, a distinctive immunological synapse forms. Here we suggest that the CD8(+) cell synapse may not simply be involved in signalling, but may have several important roles in CD8(+) effector function, including targeted delivery, and down-regulation of the cytolytic response.


Teaching adolescents safe driving and passenger behaviors: effectiveness of the You Hold the Key Teen Driving Countermeasure.
Unsafe driving and passenger behaviors place teens at increased risk for fatal and nonfatal crashes. This study evaluated the short-and long-term efficacy of the You Hold the Key (YHTK) Teen Driving Countermeasure. A two-page survey was completed by high school students at pretest, posttest, and long-term (6-month) posttest. YHTK was associated with significant immediate and long-term improvements in teen seatbelt use, safe driving, and perceived confidence in preventing drunk driving. Compared to pretests, students at immediate and long-term posttest more frequently wore seatbelts when driving or riding, required passengers to wear seatbelts, and limited the number of passengers to the number of seatbelts in the vehicle. Students were more likely at both posttests to avoid drinking and driving and to say no to riding with a friend who had been drinking. YHTK was associated with increases in safe teen driving and passenger behaviors. Success of YHTK is most notably due to its comprehensive nature. Future programs should consider comprehensive strategies when attempting to modify teen behaviors.


Multiple lifestyle risk behaviours and excess weight among adolescents in Barcelona, Spain.
We aimed to analyse the prevalence of having multiple lifestyle risk behaviours (LRB) and the potential relationship between excess weight (including overweight and obesity) and cumulative multiple LRB among adolescents in Barcelona, Spain. A cross-sectional study was performed among a representative sample of 3,114 secondary school students in Barcelona. Height and weight were objectively measured and excess weight was defined in accordance with World Health Organization criteria. Information on screen time, breakfast, physical activity and sleep duration was obtained through a self-administered questionnaire. More than 80% of the students had at least two LRBs. In compulsory schooling, the adjusted prevalence ratio (aPR) of excess weight increased with a higher number of reported LRBs (four LRBs: aPR=1.56; 95% confidence interval: 1.19-2.05). These results highlight the importance of a multiple-behaviour approach in preventive programmes aimed at reducing adolescent obesity.


Preservation and high sequence conservation of satellite DNAs suggest functional constraints.
Due to a high evolutionary turnover many satellite DNAs are restricted to a group of closely related species. Here we demonstrate that the satellite DNA family PSUB, abundant in the beetle Palorus subdepressus, is distributed in a low number of copies among diverse taxa of Coleoptera (Insecta), some of them separated for an evolutionary period of up to 60 Myr. Comparison of PSUB cloned from the species Tribolium brevicornis with the PSUB family previously characterized in Palorus subdepressus revealed high sequence conservation and absence of fixed species-specific mutations. The most polymorphic sites are those with ancestral mutations shared among clones of both species. Since the ancestral mutations contribute significantly to overall diversity, it could be proposed that a similar mutational profile already existed in an ancestral species. The pattern of variability along the satellite monomer is characterized by the presence of conserved and variable regions. The nonrandom pattern of variability as well as the absence of sequence divergence is also discerned for PRAT satellite DNA, cloned previously from two Palorus species and a distantly related Pimelia elevata. Since PRAT and PSUB are present in parallel in diverse taxa of Coleoptera, we propose that their long evolutionary preservation suggests a possible functional significance. This indication is additionally supported not only by the high evolutionary conservation of the sequences, but also by the presence of significantly conserved and variable regions along the monomers.


Complexity, stability and self-organization in natural communities.
The search for a functional relationship between diversity and stability has thus far been futile. Recent advances in cybernetics suggest that progress may be achieved if diversity, stability and redundancy are considered to be cofactors in determining the key dependent variable - the capacity for self-organization.


Analysis of Structural and Functional Differences of Glucans Produced by the Natively Released Dextransucrase of Liquorilactobacillus hordei TMW 1.1822.
The properties of the glucopolymer dextran are versatile and linked to its molecular size, structure, branching, and secondary structure. However, suited strategies to control and exploit the variable structures of dextrans are scarce. The aim of this study was to delineate structural and functional differences of dextrans, which were produced in buffers at different conditions using the native dextransucrase released by Liquorilactobacillus (L.) hordei TMW 1.1822. Rheological measurements revealed that dextran produced at pH 4.0 (MW = 1.1 * 108 Da) exhibited the properties of a viscoelastic fluid up to concentrations of 10% (w/v). By contrast, dextran produced at pH 5.5 (MW = 1.86 * 108 Da) was gel-forming already at 7.5% (w/v). As both dextrans exhibited comparable molecular structures, the molecular weight primarily influenced their rheological properties. The addition of maltose to the production assays caused the formation of the trisaccharide panose instead of dextran. Moreover, pre-cultures of L. hordei TMW 1.1822 grown without sucrose were substantial for recovery of higher dextran yields, since the cells stored the constitutively expressed dextransucrase intracellularly, until sucrose became available. These findings can be exploited for the controlled recovery of functionally diverse dextrans and oligosaccharides by the use of one dextransucrase type.


Semi-reciprocal polarization maintaining fibre coupler with distinctive transmission characteristics.
Optical couplers are very important devices in optical communication systems and optical sensor systems. Several types of optical couplers with different materials or different transmission characteristics have been reported. Here we propose a semi-reciprocal polarization maintaining fibre coupler with unique transmission characteristics, which is distinct from conventional polarization maintaining fibre couplers and polarization beam splitters, and investigate the characteristics of the coupler theoretically and experimentally. The experimental results show that for circularly and elliptically polarized input light, the proposed coupler will act both as an in-line polariser and a conventional polarization maintaining fibre coupler. The output polarization extinction ratio of the transmission arm is 31.79 dB at a centre wavelength of 841 nm. For linearly polarized input light, the coupler will merely act as a conventional 3 dB polarization maintaining fibre coupler. The unique features of the proposed coupler enables the removal of polarisers from optical sensor systems and coherent optical communication systems, and reduces the insertion loss and production cost of the optical path. Therefore there is wide application for this device in optical sensor systems and optical communication systems.


The synovial fluid hyaluronic acid in rheumatoid arthritis.
The intrinsic viscosity of hyaluronic acid in synovial fluid decreases significatively in mild and severe arthritis (24% and 37% respectively). Variation in hyaluronic acid concentration parallels the above results. Chondroitin-6-sulfate can be detected in about 30% of the arthritic fluids.


CCND1 amplification predicts sensitivity to chemotherapy and chemoradiotherapy in head and neck squamous cell carcinoma.
Cyclin D1 has been reported to be associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). FISH was performed on 58 patients. Thirty-two received neoadjuvant chemotherapy (NAC) as primary treatment and 21 with hypopharyngeal squamous cell carcinoma (HPC) received chemoradiotherapy. CCND1 amplification was identified in 31 (53%) patients and the incidence was higher in HPC (p = 0.0068). Four (31%) out of 13 patients with CCND1 amplification responded to NAC whereas the response rate in the non-amplified group was 79% (p = 0.011). CCND1 amplification with a homogeneously staining region (HSR) was accompanied by cyclin D1 protein overexpression (p < 0.0001). HPC showed HSR more frequently (p = 0.033) and the survival rate of the subgroup with HSR was lower than that without (p < 0.05). Detection of CCND1 amplification using FISH may be a useful marker of sensitivity to NAC and chemoradiotherapy for HNSCC.


A prospective cohort study on National Health Insurance beneficiaries in Ohsaki, Miyagi Prefecture, Japan: study design, profiles of the subjects and medical cost during the first year.
To examine the impact of health-related lifestyle upon medical care utilization and its costs, we conducted a cohort study among all National Health Insurance beneficiaries aged from 40 to 79 years living in the catchment area of Ohsaki Public Health Center, Miyagi, Japan. The baseline survey, using self-completed questionnaire regarding health-related lifestyle, was conducted between October and December 1994. Out of 54,996 eligible subjects, 52,029 (94.6%) responded and formed the cohort under study. Medical care utilization (number of outpatient visits and days of inpatient care) and the costs for each subject have been obtained from National Health Insurance Claim History files since January 1995. The baseline characteristics of health-related lifestyle and medical history at the study subjects were consistent with those at our another cohort subjects (so-called Miyagi cohort study; N = 47,605), which included all the residents aged from 40 to 64 years at 14 municipalities in Miyagi Prefecture, Japan conducted in 1990. The medical costs per capita in this cohort was quite compatible with the national average. This prospective cohort study would quantitatively demonstrate the economic impact of health-related lifestyle, thus would lead us to better provision of cost-effective preventive health services.


An interaction study of Ocimum sanctum L. and levetiracetam in pentylenetetrazole kindling model of epilepsy.
Ocimum sanctum L. commonly known as tulsi (synonym of Ocimum tenuiflorum L.) is widely used in Ayurveda medicine and is having multitude neuromodulatory effect including the anticonvulsant effect in acute seizure models as per previous studies. In India, it is used for the treatment of epilepsy as traditional medicine. However, its role in chronic seizure model and interaction with newer antiepileptic drugs has not been investigated, which will enhance its translational value. Current study investigated the effect of Ocimum on chronic seizure model and its interaction with levetiracetam (LEV), a newer antiepileptic drug. The adjuvant role of Ocimum sanctum hydroalcoholic extracts (OSHE) 1000 mg/kg along with LEV 300 mg/kg was studied in adult male Wistar rats with mean weight of 227.84 ± 21.68 g using pentylenetetrazole (30 mg/kg, i.p.) kindling (K) (with maximum 24 injections on alternate days and challenge on 7th-day). Along with seizure score, neurobehavioral, brain tissue oxidative stress and histopathology status were assessed. Pharmacokinetic interaction was assessed between LEV and OSHE after 14 days of drug treatment. K-LEV + OSHE had least seizure score during kindling and on the pentylenetetrazole-challenge test (p=0.031) than other kindling groups. Seizure protection was more in K-LEV + OSHE (85.72%) than others (K-LEV-42.86%, K-OSHE-42.86%, and K-Control-28.58%). Ocimum treated groups had better memory retention potential as evident from Morris water maze (MWM), passive avoidance test but not in an elevated plus maze test. Oxidative-stress was lower in Ocimum treated groups than K-Control group. As per histopathology, K-LEV + OSHE group had the least neuronal degeneration among kindling groups. There was no significant pharmacokinetic interaction between LEV and OSHE, except increased Tmax in LEV + OSHE group than LEV alone (p=0.009). Ocimum per se and combination with levetiracetam treatment exerted better seizure control, memory retention, oxidative stress reduction, and neuronal structure preservation than kindling control group. There was a very minimal drug interaction between Ocimum and LEV. So, Ocimum as an adjuvant to LEV may be shelpful in enhancing the antiepileptic effect and also in minimizing the adverse effects.


The protective activity of mesothelial cells against peritoneal growth of gastrointestinal tumors: The role of soluble ICAM-1.
In this project we examined how the presence of human peritoneal mesothelial cells (HPMCs) modifies (supports or inhibits) colorectal and pancreatic cancer cell progression in mice peritoneal cavity. Experiments were performed using primary, omentum-derived HPMCs, commercially available colorectal (SW-480) and pancreatic (PSN-1) cancer cells, and immunocompromised SCID mice. Tumor growth within the peritoneal cavity was monitored using bioluminescence. Adhesion of the cancer cells to HPMCs was examined using a fluorescence-based method, while the incidence of apoptosis was quantified using flow cytometry. Experiments showed that SW480 and PSN-1 cells formed tumors in vivo at higher efficiency when they were injected alone than in the presence of HPMCs. In vitro investigations confirmed that firm adhesion of SW480 and PSN-1 cells to HPMCs is mediated by interactions between ICAM-1 and CD43. They also revealed that IL-6 and TNFα up-regulate the expression of cell-bound ICAM-1 and the secretion of soluble ICAM-1 (sICAM-1). The basal release of sICAM-1 by HPMCs positively correlated with the expression of the cell-bound molecule. sICAM-1 inhibited dose-dependently the adhesion of SW480 and PSN-1 cells to HPMCs. Cancer cells that did not adhere to HPMCs displayed increased activity of caspase-3 and -9, increased incidence of apoptosis, and an inability to re-adhesion, as compared with their intact counterparts not exposed to sICAM-1. Our findings indicate that under certain conditions HPMCs are capable of inhibiting growth of gastrointestinal tumors in a mechanism involving the anti-adhesive capabilities of sICAM-1.


Dynamic aphasia with emerging agrammatism, anomia, and aberrant frontal behaviors in a case of atypical parkinsonism.
A 57-year-old man presented with dynamic aphasia with evolving agrammatism and anomia. Additionally, he exhibited emerging atypical parkinsonism and features of behavioral variant frontotemporal dementia. Insights pertinent to this complex clinical presentation are discussed.


Assessment of real-time polymerase chain reaction detection of Acanthamoeba and prognosis determinants of Acanthamoeba keratitis.
To evaluate the diagnostic value of real-time polymerase chain reaction (PCR) for detecting Acanthamoeba in eyes diagnosed with Acanthamoeba keratitis (AK) by conventional tests. In addition, to determine the preoperative prognosis-determining factors in eyes with AK. Retrospective, cross-sectional study. A total of 104 eyes of 103 patients who were diagnosed with AK or with bacterial or bacteria-associated keratitis (BK) by conventional tests. Twenty-nine eyes with AK and 75 eyes with BK were evaluated for Acanthamoeba and bacterial DNA by real-time PCR. The Acanthamoeba copy numbers, bacterial load, and clinical parameters in the patients with AK were assessed for those significantly associated with poor outcome, that is, final visual acuity of <20/50 or requiring keratoplasty, by logistic regression analysis. Acanthamoeba DNA copy number, bacterial DNA copy number, and odds ratio (OR) for poor prognosis. The detection of amoebic DNA was 50 times more sensitive by real-time PCR than by conventional cyst counting. The Acanthamoeba copy numbers at the first visit (mean: 4.7×10(5)±3.2×10(5) copies) were significantly correlated with the AK stage, and both were significant risk factors for a poor outcome. The Acanthamoeba DNA copy numbers at the first visit and AK stage had a significantly high risk for poor outcome (OR of Acanthamoeba DNA copy per logarithm of copy numbers: 3.48, 95% confidence interval [CI], 1.04-111.63, P<0.05; OR of AK stage: 2.8 per stage increase, 95% CI, 1.07-7.30, P<0.05, after adjustment of age). In the AK cases with poor outcome, the amoebic DNA was not reduced by more than 90% after 1 month of treatment. The weak amoebic reduction was significantly associated with advanced AK stages or previous use of steroids. Bacterial 16S rDNA was detected in 53.6% of the eyes with AK, but it was not associated with any risk for refractoriness. Real-time PCR was effective in detecting and managing AK. The Acanthamoeba copy number and AK stage at the first visit were significantly associated with poor outcome. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Primary non-refluxing megaureters.
Megaureters may be primary or secondary, and the dilatation may be due to obstruction or reflux, or both or neither. The cause of primary obstructed megaureter is the aperistaltic and narrowed pre-vesical portion of the ureter. The inner sheath of the terminal ureter generally shows a reduced amount of longitudinal smooth muscle bundles and an increased amount of collagen. Primary non-refluxing megaureters represent 23% of all prenatal diagnoses of hydronephrosis. They are more common in males and on the left side, and in 25% are bilateral. In older children they may become symptomatic. The diagnostic work up should include an ultrasound, a micturating cystourethrogram and an isotopic renogram. Most primary megaureters regress spontaneously or remain stable without compromising renal function, but 10-25% require surgery because of a progressive reduction in renal function or increasing dilatation, or because they become symptomatic. The basic principles of surgical repair include: resection of the obstructing segment, reduction in size of the dilated ureter, and re-implantation into the bladder using an anti-reflux technique.


Second primary lung malignancy in head and neck cancer patients.
Second primary lung cancer (SPLC) is generally of poor prognosis in patients presenting with head and neck cancer. Between January 2000 and June 2008, 39 patients with head and neck squamous-cell carcinoma (HNSCC) patients diagnosed with SPLC were included. Fourteen SPLC were classified as synchronous and 25 as metachronous. SPLC and HNSCC staging correlated (P=0.0496). Patients with metachronous tumor showed longer median overall survival than those with synchronous tumor (92.9 months versus 15.7 months; Hazard ratio (HR), 0.323; 95% CI, 0.042-0.559; P=0.0045). In the subgroup of 11 patients with SPLC diagnosed more than 5 years after HNSCC, prognosis was better (128.1 versus 29.7 months; HR, 0.288; 95% CI, 0.053-0.353; P<0.0001). In the present study, in contrast to the literature, improved prognosis and survival were found in the subgroup in which SPLC developed more than 12 months after initial HNSCC diagnosis, and even more specifically in that in which SPLC developed more than 5 years after initial HNSCC diagnosis. SPLC in HNSCC is generally described as unequivocally aggressive and of poor prognosis. Metachronous SPLC, however, especially when diagnosed more than 5 years after HNSCC, was clearly associated with better prognosis.


Apolipoprotein A-I metabolism in cholesteryl ester transfer protein transgenic mice. Insights into the mechanisms responsible for low plasma high density lipoprotein levels.
Expression of simian cholesteryl ester transfer protein (CETP) in C57BL/6 mice causes the animals' high density lipoprotein (HDL) levels to decrease. The purpose of these studies was to determine how CETP expression caused that reduction. Chemical analysis showed that the HDL of the CETP transgenic mice had about twice as much triglyceride and only about 60% as much cholesteryl ester as the HDL from the C57BL/6 mice. Both strains of mouse had high levels of a circulating lipase. When plasma from the mice was incubated at 37 degrees C for 5 h, the triglycerides in the HDL were hydrolyzed, and apoA-I was shed from the particle. However, apoA-I was shed from the CETP HDL more rapidly than it was shed from the C57BL/6 HDL. Because "free" apoA-I is rapidly cleared by the kidney, increased production of free apoA-I would be expected to shorten the average life span of apoA-I in the mouse. Kinetic analyses indicated that the life span of apoA-I was significantly reduced in the CETP transgenic mice. It was concluded that CETP expression enriched the core of the HDL with triglyceride, which rendered it vulnerable to lipolysis, causing apoA-I to be shed from the particle. That shortened the life span of apoA-I in the CETP mice, which led to lower plasma levels of the protein.


Interstitial lung disease and adult-onset Still's disease.
Adult-onset Still's disease is an uncommon rheumatological syndrome with a diversity of signs and symptoms. Pulmonary manifestations described are pleuritis and usually transient radiologic infiltrations. The patient presented in this case report had biopsy-proven lung fibrosis when adult-onset Still's disease was diagnosed. Three years after diagnosis, the patient developed clinical signs of the interstitial lung disorder. Radiological and histological progression was observed. Other causes of interstitial lung disorders were excluded. Clinicians should be aware that interstitial lung disease can be a complication of adult-onset Still's disease and can compromise the clinical status of the patient.


Selective repression of Notch pathway target gene transcription.
The Notch signaling pathway regulates metazoan development, in part, by directly controlling the transcription of target genes. For a given cellular context, however, only subsets of the known target genes are transcribed when the pathway is activated. Thus, there are context-dependent mechanisms that selectively maintain repression of target gene transcription when the Notch pathway is activated. This review focuses on molecular mechanisms that have been recently reported to mediate selective repression of Notch pathway target gene transcription. These mechanisms are essential for generating the complex spatial and temporal expression patterns of Notch target genes during development.


Histopathologic evidence of tumor regression in the axillary lymph nodes of patients treated with preoperative chemotherapy correlates with breast cancer outcome.
The benefits of primary tumor downstaging and assessment of chemoresponsiveness have resulted in expanded applications for induction chemotherapy. However, the pathologic evaluation and prognostic significance of response in preoperatively treated lymph nodes have not been defined. The axillary lymph nodes of 71 patients with locally advanced breast cancer treated with induction chemotherapy were evaluated for histological evidence of tumor regression as defined by the presence of nodal fibrosis, mucin pools, or aggregates of foamy histiocytes. Complete pathologic response in the breast and axilla occurred in 10 patients (14%); 19 (26.8%) had evidence of tumor regression in 1 or more lymph nodes. Patients without nodal metastases and no evidence of tumor regression had the best outcome (median disease-free survival, 31.5 months; relapse rate, 27%). Patients with residual nodal metastases and no evidence of treatment effect had the worst outcome (median disease-free survival, 19.8 months; relapse rate, 55%). The median disease-free survival was 22.1 months, and the relapse rate was 32% for patients with histopathologic evidence of tumor regression in the axillary lymph nodes. Detection of treatment effect in axillary lymph nodes after induction chemotherapy identifies a subset of patients with an outcome intermediate between that of completely node-negative and node-positive patients. The axillary lymph nodes of patients receiving preoperative chemotherapy should be routinely analyzed for the presence of these features.


Hybrid medial patellofemoral ligament reconstruction using the semitendinous tendon for recurrent patellar dislocation: minimum 3 years' follow-up.
The purpose of this study was to evaluate the results of a new hybrid medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar dislocation. Hybrid MPFL reconstruction by use of the semitendinous tendon was performed in 12 knees with recurrent patellar dislocation. The results were evaluated at a minimum follow-up of 3 years (mean, 4.2 years). According to the grading system of Insall et al., the results were classified as excellent in 8 knees (66%), good in 2 (17%), and fair in 2 (17%), with none being classified as poor. The mean Kujala score was 56.3 points (range, 29 to 82) preoperatively and 96.0 points (range, 84 to 100) at follow-up. There were no patients with recurrent dislocation and subluxation. No knees had a positive apprehension sign, and there were no postoperative complications. At a midterm follow-up, hybrid MPFL reconstruction by use of the semitendinous tendon for recurrent patellar dislocation should be considered as an effective operation for cases without severe predisposing factors. Level IV, therapeutic case series, no or historical control group.


[Drug resistance of Mycobacteria tuberculosis in patients with new-onset pulmonary tuberculosis].
Statistics for the last 6 years show a trend to growing number of new cases with tuberculosis of the lungs with drug-resistant pathogen. In recurrent tuberculosis multiple drug resistance (MDR) was three times higher than in new cases. Treatment efficacy depended on MDR and patients' compliance. The results of the basic treatment course were unstable: many patients had exacerbation within 3-4 years after therapy, many patients died, especially those with M. tuberculosis resistant to many drugs.


Genomewide clonal analysis of lethal mutations in the Drosophila melanogaster eye: comparison of the X chromosome and autosomes.
Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes.


Dietary fiber, whole grains, carbohydrate, glycemic index, and glycemic load in relation to risk of prostate cancer.
The relationships between dietary fiber, whole grains, carbohydrate, glycemic index (GI), glycemic load (GL), and prostate cancer risk are unclear. We conducted a systematic review and meta-analysis to investigate these associations. Relevant studies were identified by a search of PubMed database and EMBASE database up to April 2015. A random effects model was used to calculate the summary relative risks (RRs) and their corresponding 95% confidence intervals (CIs). Twenty-seven epidemiological studies (18 case-control studies and nine cohort studies) were included in the final analysis. The pooled RRs of prostate cancer were 0.94 (95% CI 0.85-1.05, P=0.285), 1.13 (95% CI 0.98-1.30, P=0.095), 0.96 (95% CI 0.81-1.14, P=0.672), 1.06 (95% CI 0.96-1.18, P=0.254), and 1.04 (95% CI 0.91-1.18, P=0.590) for dietary fiber, whole grains, carbohydrate, GI, and GL, respectively. There was no evidence of significant publication bias based on the Begg's test and Egger's test. The findings of this meta-analysis indicate that, based on available information, dietary fiber, whole grains, carbohydrate, GI, and GL are not associated with the risk of prostate cancer.


Optimizing the control of apoptosis by amide/triazole isosteric substitution in a constrained peptoid.
Apoptosis is a biological process relevant to several human diseases that is strongly regulated through protein-protein complex formation. We have previously reported a peptidomimetic compound as potent apoptotic modulator. Structural studies of this compound showed the presence of cis/trans isomers of the exocyclic tertiary amide bond in slow exchange. This information encouraged us to perform an isosteric replacement of the amide bond by a 1,2,3-triazole moiety, where different substitution patterns would mimic different amide rotamers. The syntheses of these restricted analogs have been carried out using the Ugi multicomponent reaction followed by an intramolecular cyclization. Unexpectedly, for one of the proposed structures, a novel β -lactam compound was formed. All compounds showed to efficiently inhibit apoptosis, in vitro and in cellular extracts, with slight differences for the corresponding regioisomers. We propose the binding to Apaf-1 as the inhibition mechanism.


Profiles in fibromyalgia: algometry, auditory evoked potentials and clinical characterization of different subtypes.
The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.


Formation of thomasidioic acid from dehydrosinapinic acid dilactone under neutral conditions, and a remaining inhibitory activity against peroxynitrite-mediated protein nitration.
Dehydrosinapinic acid dilactone (1) was converted to thomasidioic acid (3) and (E,E)-2,3-bis(3,5-dimethoxy-4-hydroxybenzylidene)succinic acid (4) via an alpha,beta-unsaturated gamma-lactone type dimer (2) in phosphate buffer (pH 7.4). A study of the reaction mechanism was accomplished by observing the reaction of methyl ester of 2. The lignans (3, 4) were also prevented the peroxynitrite-mediated protein nitration.


Protein-protein interaction network of E. coli K-12 has significant high-dimensional cavities: new insights from algebraic topological studies.
As a model system, Escherichia coli has been used to study various life processes. A dramatic paradigm shift has occurred in recent years, with the study of single proteins moving toward the study of dynamically interacting proteins, especially protein-protein interaction (PPI) networks. However, despite the importance of PPI networks, little is known about the intrinsic nature of the network structure, especially high-dimensional topological properties. By introducing general hypergeometric distribution, we reconstruct a statistically reliable combined PPI network of E. coli (E. coli-PPI-Network) from several datasets. Unlike traditional graph analysis, algebraic topology was introduced to analyze the topological structures of the E. coli-PPI-Network, including high-dimensional cavities and cycles. Random networks with the same node and edge number (RandomNet) or scale-free networks with the same degree distribution (RandomNet-SameDD) were produced as controls. We discovered that the E. coli-PPI-Network had special algebraic typological structures, exhibiting more high-dimensional cavities and cycles, compared to RandomNets or, importantly, RandomNet-SameDD. Based on these results, we defined degree of involved q-dimensional cycles of proteins (q-DCprotein ) in the network, a novel concept that relies on the integral structure of the network and is different from traditional node degree or hubs. Finally, top proteins ranked by their 1-DCprotein were identified (such as gmhB, rpoA, rplB, rpsF and yfgB). In conclusion, by introducing mathematical and computer technologies, we discovered novel algebraic topological properties of the E. coli-PPI-Network, which has special high-dimensional cavities and cycles, and thereby revealed certain intrinsic rules of information flow underlining bacteria biology.


Rhinologic applications of laser surgery.
The use of lasers in the treatment of rhinologic conditions is described. Both intranasal and extranasal laser applications are discussed. The choice of an appropriate laser to suit the clinical situation is also examined.


A dataset on social media users' engagement with religious misinformation.
This dataset comprises Facebook data on five cases of religious misinformation in Bangladesh. To the best of our knowledge, it is the first publicly accessible dataset on Facebook-based religious misinformation in the country, featuring 7350 comments contributed by unique users. As online religious misinformation has been implicated in causing interreligious violence and tension in Bangladesh, this dataset can offer crucial insights into how social media is being exploited to foment such events. It may also help advance policy reform and activism to protect human rights and prevent the spread of religious misinformation.


Evaluation of referrals from general practice to a neurological department.
The presence of neurological deficits as obtained from clinical examination increases the likelihood of detecting serious underlying brain disorders. In this study, we assessed the frequency of reported clinical neurological examination in patients referred to neurology. We consecutively evaluated referrals to a neurological centre during a 6-month period. From a total of 716 patients, 377 (51%) had an examination reported in the referral letter. Clinical examinations were reported more often in patients with musculo-skeletal disorders compared with others, P = 0.0001. Examination was less likely to be reported in those with a history of disturbed consciousness. By showing that only about half of the patients had an examination reported, the study demonstrates that the process of selecting those with a high priority for a secondary neurological service can be improved.


Explaining Fairness : Results from an Experiment in Guinea.
Fairness is undoubtedly an essential normative concept in humans and promotes cooperation in human societies. The fact that fairness exists is puzzling, however, because it works against the short-term interest of individuals. Theories of genetic evolution, cultural evolution, and gene-culture coevolution identify plausible mechanisms for the evolution of fairness in humans. Such mechanisms include kin selection, the support of group-beneficial moral norms through ethnic markers, free partner choice with equal outside options, and free partner choice with reputation as well as spite in small populations. Here, we present the results of a common-pool resource game experiment on sharing. Based on data from 37 multiethnic villages in a subsistence agricultural population in Foutah Djallon, Guinea, we show that fair behavior in our experiment increased with increasing ethnic homogeneity and market integration. Group size and kinship had the opposite effect. Overall, fair behavior was not conditional on reputation. Instead, the ability of the different village populations to support individuals' fairness in situations lacking the opportunity to build a positive reputation varied significantly. Our results suggest that evolutionary theory provides a useful framework for the analysis of fairness in humans.


The safety and efficacy of tripotassium dicitrato bismuthate (De-Nol) maintenance therapy in patients with duodenal ulceration.
Seventy-one patients whose duodenal ulcers had healed after a 4-week treatment period with tripotassium dicitrato bismuthate (TDB) were randomly allocated to receive maintenance treatment with either one TDB swallow tablet nocte (equivalent to 120 mg Bi2O3) or an identical placebo. During 12 months of follow-up, no side-effects were reported by TDB-treated patients, blood bismuth levels did not rise above discontinuation threshold concentrations (greater than 50 micrograms/L in the first 6 months, or greater than 100 micrograms/L in the second 6 months), and there were no adverse effects on haematological or biochemical indices. Ulcer relapse was significantly less in TDB-treated patients (P less than 0.025). Cumulative relapse rates at 6 and 12 months were 51% and 66%, respectively, for placebo-treated patients and 26% and 31%, respectively, for those who received TDB. It is likely that TDB is a safe and effective maintenance treatment for patients with duodenal ulcer disease.


Emergency Triage Assessment and Treatment Plus (ETAT+): adapting training to strengthen quality improvement and task-sharing in emergency paediatric care in Sierra Leone.
Over the past 25 years Sierra Leone has made progress in reducing maternal and child mortality, but the burden of preventable paediatric deaths remains high. Further progress towards achieving the Sustainable Development Goals will require greater strengthening of the health care system, including hospital care for perinatal and paediatric conditions. Emergency Triage Assessment and Treatment Plus (ETAT+) may offer a useful tool. The five-day ETAT+ course was adapted as a six-month programme of in-situ training and mentoring integrated with patient flow and service delivery improvements in 14 regional and district government hospitals across the country. Nurses were trained to carry out the initial resuscitation and assessment of the sick paediatric patient, and to administer the first dose of medication per protocol. The course was for all clinical staff; most participants were nurses. The intervention was associated with an improvement in the quality of paediatric care and a reduction in mortality. In 2017 mortality decreased by 33.1%, from 14.5% at baseline to 9.7% after six months of the intervention. Mortality at the start of the 2018 intervention was 8.5% and reduced over six months to 6.5%. Care quality indicators showed improvement across the two intervention periods, with some evidence of sustained effect. These results suggest that adapted ETAT+ training with in-situ mentoring alongside improved patient flow and service delivery supports improvements in the quality of paediatric care in Sierra Leonean hospitals. ETAT+ may provide an affordable framework for improving the quality of secondary paediatric care in Sierra Leone and a model of nurse-led resuscitation may allow for prompt and timely emergency paediatric care in Sierra Leonean hospitals where there are fewer physicians and other resources for care.


Fabrication of titania/calcium alginate nanocomposite matrix for efficient adsorption and photocatalytic degradation of malachite green.
This work aims to examine the two techniques' efficiency for the elimination of malachite green (MG) by photocatalytic degradation and adsorption onto synthesized solid nanomaterials. Three solid samples were prepared as calcium alginate (AG), nanotitania (NT), and nanotitania/calcium alginate composite (TG). The morphological and physicochemical characteristics of the solid nanomaterials were investigated by XRD, TGA, DRS, FTIR, pHPZC, nitrogen adsorption/desorption isotherm, SEM, and TEM. The main experimental conditions were determined for sample dose, shaking time, pH, initial malachite green concentration, temperature, ionic strength, and UV lamp power. The resulting data proved that TG attained the higher adsorption capacity (252.52 mg/g) at 40 °C. The adsorption of MG was well fitted by Langmuir, Temkin, Dubinin-Radushkevich, pseudo-second order, intra-particle diffusion, and Elovich models onto all the prepared samples, confirming the endothermic, spontaneous, and favorable adsorption process. The maximum degradation percent (99.6 %) of MG was achieved by using 1.0 g/L as a catalyst dose, 10 mg/L of initial MG concentration, and 33 W for TG. The photodegradation of MG was well fitted by Eyring-Polanyi and Arrhenius models onto the surface of catalyst. The TG reusability resulted in a decrease in the degradation efficiency by 9.8 %, indicating its great capacity as the first nanotitania/calcium alginate nanocomposite used in removing MG from wastewater by two technologies in the same article.


Human-type A-B-O blood group antigens of Ethiopian vervet monkeys (Cercopithecus aethiops) in the wild.
Human type A-B-O blood group antigens were tested in a local population of Ethiopian vervet monkeys (Cercopithecus aethiops). One animal was of group AB, the others were A. This represents a lower rate of polymorphism at this locus than has been observed among South African populations of the same species.


Effects of host maturity and prior exposure history on the production of Neospora caninum oocysts by dogs.
To investigate whether dogs shed Neospora caninum oocysts more than once, five dogs with a previous history of shedding oocysts were fed infected bovine tissues. Two of three dogs shed oocysts when they were re-exposed 18-20 months after the first challenge; two other dogs re-exposed earlier, only 8 months after the primary exposure, did not produce oocysts. These results suggest that dogs may become refractory to shedding N. caninum oocysts for a period approximately between 8 and 18 months after a primary infection; however, this possibility requires statistical validation by testing of more dogs. The development of a high antibody titer did not ensure that a dog would completely resist shedding oocysts after consuming an infected meal. Oocyst production was also compared between puppies and adult dogs with primary infections. Twelve puppies (three from the present study and nine from a previous study) shed significantly more oocysts (mean: 166,400) compared with five adult dogs following primary exposure (mean: 2900), indicating that a dog's age can influence N. caninum oocyst production (P=0.02).


Influence of glutathione-related genetic variants on the oxidative stress profile of Mexican patients with psychotic disorders.
The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. GSH levels were significantly reduced and, conversely, GPx activity was higher in PD patients compared to controls. GCLC_GAG-7/9 genotype (OR=4.3, CI95=1.40-14.31, p=0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR=6.09, CI95=1.93-22.59, p=0.003) were found as risk factors for psychosis. The genetic variants were not related to clozapine/N-desmethylclozapine levels or to metabolic ratio. GCLC variants were associated with the oxidative stress profile of PD patients raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal.


Salinity responses of benthic microbial communities in a solar saltern (Eilat, Israel).
The salinity responses of cyanobacteria, anoxygenic phototrophs, sulfate reducers, and methanogens from the laminated endoevaporitic community in the solar salterns of Eilat, Israel, were studied in situ with oxygen microelectrodes and in the laboratory in slurries. The optimum salinity for the sulfate reduction rate in sediment slurries was between 100 and 120 per thousand, and sulfate reduction was strongly inhibited at an in situ salinity of 215 per thousand. Nevertheless, sulfate reduction was an important respiratory process in the crust, and reoxidation of formed sulfide accounted for a major part of the oxygen budget. Methanogens were well adapted to the in situ salinity but contributed little to the anaerobic mineralization in the crust. In slurries with a salinity of 180 per thousand or less, methanogens were inhibited by increased activity of sulfate-reducing bacteria. Unicellular and filamentous cyanobacteria metabolized at near-optimum rates at the in situ salinity, whereas the optimum salinity for anoxygenic phototrophs was between 100 and 120 per thousand.


Effects of the systemic administration of kainic acid and NMDA on exploratory activity in rats.
In spite of growing evidence for the involvement of the glutamatergic system in mammal's locomotion, studies on behavioral effects induced by the systemic administration of excitatory amino acids not associated to convulsions are lacking. In the present work, the effect of one single systemic administration of kainic acid (KA) (9 mg/kg, IP) or NMDA (100 mg/kg, IP) on exploratory activity in the rat during 6 consecutive days was studied. Separation of exploratory activity in fast (FM) and slow movements (SM) and rearings (R), together with the analysis of those variables during both the light and dark periods of the light-dark cycle, allowed finding specific drug-induced effects. KA produced an acute short-lasting increase in exploratory activity, only significant for FM. On the other hand, NMDA produced an acute short-lasting depressant effect on FM, SM, and R, followed during the next 2 days by a long-lasting increase in exploratory activity, only significant for FM during the dark period. These results underline the importance of using repeated testing during both light and dark periods of the light-dark cycle when analyzing drug-induced changes on exploratory activity.


A technique for glottic reconstruction following vertical partial laryngectomy.
In order to obtain a good phonatory function by glottic reconstruction following vertical partial laryngectomy, the following basic conditions should be satisfied: (1) adequate glottic closure should occur during phonation; (2) the top of the bulge constructed on the operated side should be located at the level of the vocal fold in order to prevent ventricular fold vibration; and (3) the surface of the bulge should be smooth. A technique for glottic reconstruction which appears to meet these requirements is described. The sternohyoid muscle is dissected at the requirements is described. The sternohyoid muscle is dissected at the level 5 cm below the vocal fold, and the upper portion is used as a single pedicled flap. The muscle flap is bent approximately 90 degrees at the level of the upper border of the cricoid cartilage and inserted into the intralaryngeal wound so as to make a large bulge. The muscle flap is covered by hypopharyngeal mucosa or a free graft of lip mucosa.


Visual motion: dendritic integration makes sense of the world.
Flies use a system of specialised neurons to read the patterns of visual motion - optic flow - induced by the their movements. Recent experiments illustrate how the dendrites of these neurons reach out to assemble patterns of optic flow and encode them reliably.


Involution of spontaneous benign prostatic hyperplasia in the dog under the influence of chronic treatment with a LHRH agonist.
Eight dogs with spontaneous benign prostatic hyperplasia were treated with daily subcutaneous injections of 25 micrograms of Buserelin, (D-Ser(TBU)6,des-Gly-NH2(10))ethylamide during 3 months. Prostate weight before treatment was estimated by tridimensional measurements during open surgery. After 3 months of treatment, prostate weight was decreased by 50-60% In two castrated control animals, prostate weight decreased about 70% after 3 months. Histological pattern in prostates from castrated or Buserelin-treated animals was similar and indicated considerable atrophy of glandular epithelium and predominance of stroma. At the same time, testes weight decreased with complete disappearance of spermatogenic activity. Acid phosphatase and arginine esterase activity levels, two markers of androgenic action in the prostate, were similar after Buserelin or castration. Steroid receptors for androgens, estrogens, and progesterone also behaved similarly under the influence of Buserelin and castration.


A three-year evaluation of hemostatic function in Singaporean Norplant-2 rod acceptors.
A longitudinal study of hemostatic function was carried out on 100 Singaporean acceptors using Norplant-2 rods for contraception. The results at the end of three years indicate a possible increased predisposition to thrombosis, as evidenced by significant increases in platelet count and aggregability. The prothrombin time (PT) and activated partial thromboplastin time (APTT) continued to remain shortened at the end of three years of use. There was also a general fall in most of the vitamin K coagulation factors. There is thus still an indication of a possible enhanced potential for hypercoagulation at the end of three years of Norplant-2 rod use.


Individual muscle force estimations using a non-linear optimal design.
In order to estimate individual muscle forces during human movement a mathematically underdetermined system, representing the human musculoskeletal system, was solved using a non-linear optimization algorithm. The load sharing between muscles was made to depend upon the instantaneous contractile conditions of the muscles, a feature not incorporated in comparable non-linear optimal designs reported in the literature. The optimization algorithm was formulated as a convex system which guarantees a unique solution at the global minimum. The strengths and weaknesses of the present optimization algorithm were evaluated and compared to the classical algorithm reported by Crowninshield and Brand (J. Biomech., 14 (1981) 793-801).


The effects of EMG-assisted relaxation training with hyperkinetic children: a behavioral alternative.
Six developmentally hyperkinetic children, ages 6 to 9, participated in either an A-B-A-B-A or an A-B-A-BC-A research design to evaluate the effect of EMG-assisted relaxation training in the acquisition of self regulatory skills to decrease hyperkinetic behavior. Descriptive verbal feedback regarding subject performance was provided during the BC phase in addition to the continuous rate-proportional auditory feedback normally available. Posttraining psychological assessment yielded significant gains for the experimental group on various visual motor tasks at the .05 level. All six subjects significantly decreased EMG activity across the 15 sessions. In a follow-up, five of the six maintained such activity at or below levels reached at the conclusion of the study. Five out of six made significant behavioral improvements at home during training and were maintaining these at the follow up. One out of four made significant improvements in school behavior during training, with five out of six exhibiting such improvements at the follow-up during the next school year. Auditory feedback was effective at the .05 level; the benefit of the verbal feedback, however, was not demonstrated. Two subjects were maintained on stimulant medication, one with a slight dose reduction during training. According to the observations of their parents and teachers, four subjects for whom medication had been recommended prior to the training were subsequently judged not to need it at the time of the follow-up.


A forward model for maximum expiration.
The maximum expiratory flow-volume (MEFV) curve is a sensitive test of respiratory mechanics. Several mathematical models for forced expiration have been developed, but they suffer from various shortcomings. It is impossible to calculate the parts of the MEFV curve beyond the flow limiting conditions and computational algorithms do not allow a direct calculation of maximal flow. In the present work a complex, nonlinear forward model, including exciting signal and static recoil pressure-lung volume descriptions and 132 parameters, has been constructed. Direct determination of maximum flow is achieved by means of successive approximation algorithm. The model enables prediction of flow during forced expiration in the whole range of forced vital capacity.


[Effect of glucosidorum Tripterygii tororum on interleukin-6 and interleukin-8 on human peripheral mononuclear cells of healthy subjects].
To explore the effect of glucosidorum Tripterygii tororum (GTT). Using different techniques of cell culture, the function of GTT in comparing with that of hydrocortison (HC) on interleukin (IL)-6 and -8 production by peripheral mononuclear cells of healthy Subjects was investigated. (1) Both of GTT and HC inhibited IL-6, IL-8 production, the effect of GTT being stronger when the dosage was higher than 1 microgram/ml; (2) In the isolated cells culture, the effect of GTT was similar to that of HC, but in the whole blood culture, the effect of GTT was much weaker than that of HC. (1) GTT inhibited interleukin production in a dose-dependent manner; (2) The sensitivity of interleukin to drugs was different in different culture conditions; (3) The anti-inflammatory effect of GTT was related to the interleukin inhibition, but the mechanism might be different from that of HC.


Increased Awakenings From Non-rapid Eye Movement Sleep Explain Differences in Dream Recall Frequency in Healthy Individuals.
Dreaming is a universal experience, yet there is considerable inter-individual variability in dream recall frequency (DRF). One dominant model, the "arousal-retrieval" model, posits that intra-sleep wakefulness is required for dream traces to be encoded into long-term storage, essentially proposing that a better memory for dreams underlie increased DRF. A recent study utilizing polysomnography combined with an event-related potentials paradigm, provides direct support for this model by demonstrating increased intra-sleep wakefulness in a healthy population by comparing high frequency recallers (HFRs) and low frequency recallers (LFRs). Another study by the same group demonstrated increased regional cerebral blood flow in regions associated with dream production, supporting the premise that HFRs also may produce more dreams. This study investigated the profile of nocturnal awakenings and dream production in healthy HFRs and LFRs. Hypothesis (1a): HFRs will spend significantly more time awake after sleep onset; (1b): HFRs will experience significantly more awakenings across the night, and from rapid eye movement (REM) sleep in particular; (2) HFRs will have significantly higher rates of dream production across the night as measured by REM density. We studied two groups of healthy adults: HFRs (n = 19) and LFRs (n = 17) who underwent polysomnographic recordings on two non-consecutive nights. Hypothesis (1a) was confirmed: HFRs spent significantly more time awake after sleep onset. Hypothesis (1b) was partially confirmed: HFRs experienced significantly more awakenings across the night; however, awakenings from REM sleep were comparable. Interestingly, HFRs had significantly more awakenings, as well as a higher number of longer awakenings, from non-rapid eye movement (NREM) stage 2 sleep. Hypothesis (2) was not confirmed: There was no significant difference in rates of REM density between groups. This is the first study to provide evidence that awakenings from NREM 2 sleep might underlie increased DRF in HFRs. This finding coupled with null findings in relation to REM sleep variables, support the premise that inter-individual variability in DRF cannot be ascribed to differences in REM sleep parameters in healthy individuals. Instead, the data indicates that awakenings from NREM sleep is of particular importance in relation to DRF in a healthy population.


Toxoplasma gondii infection triggers ongoing inflammation mediated by increased intracellular Cl- concentration in airway epithelium.
Toxoplasma gondii is a widespread parasitic protozoan causing toxoplasmosis including pulmonary toxoplasmosis. As the first line of host defense, airway epithelial cells play critical roles in orchestrating pulmonary innate immunity. However, the mechanism underlying the airway inflammation induced by the T. gondii infection remains largely unclear. This study demonstrated that after infection with T. gondii, the major anion channel located in the apical membranes of airway epithelial cells, cystic fibrosis transmembrane conductance regulator (CFTR), was degraded by the parasite-secreted cysteine proteases. The intracellular Cl- concentration ([Cl-]i) was consequently elevated, leading to activation of nuclear factor-κB (NF-κB) signaling via serum/glucocorticoid regulated kinase 1. Furthermore, the heightened [Cl-]i and activated NF-κB signaling could be sustained in a positive feedback regulatory manner resulting from decreased intracellular cAMP level through NF-κB-mediated up-regulation of phosphodiesterase 4. Conversely, the sulfur-containing compound allicin conferred anti-inflammatory effects on pulmonary toxoplasmosis by decreasing [Cl-]i via activation of CFTR. These results suggest that the intracellular Cl- dynamically modulated by T. gondii mediates sustained airway inflammation, which provides a potential therapeutic target against pulmonary toxoplasmosis.


The number of polypeptide chains in the rod domain of bovine epidermal keratin.
The physical properties of the alpha-helix enriched particle obtained by limited proteolysis of epidermal keratin have been examined. Molecular weights in benign and dissociating solvents, hydrodynamic measurements and chemical cross-linking experiments indicate that the particle has four polypeptide chains. It is proposed that the helical particle is assembled from a pair of two-stranded alpha-helical ropes.


Determination of nucleosides and nucleotides in baby foods by hydrophilic interaction chromatography coupled to tandem mass spectrometry in the presence of hydrophilic ion-pairing reagents.
In this work we propose a rapid and efficient method for the joint determination of nucleosides and nucleotides in dairy and non-dairy baby foods based on hydrophilic interaction chromatography coupled to tandem mass spectrometry in the presence of diethylammonium (DEA) as a hydrophilic ion-pairing reagent (IP-HILIC-MS/MS). Sample treatment of the baby food included dilution with water and centrifugal ultrafiltration (CUF) with an additional washing step that notably improved the global performance of the process. Later dilution of the extract with acetonitrile allowed adequate separation in the HILIC system. With the proposed treatment, we obtained extraction recoveries higher than 80% and, additionally, no matrix effects were observed. The CUF-IP-HILIC-MS/MS method was validated according to the 2002/657/EC decision and was used for the quantification of nucleotides and nucleosides in sixteen samples of commercial baby foods.


The Relationship Between Autism and Pitch Perception is Modulated by Cognitive Abilities.
Previous studies reported mixed findings on autistic individuals' pitch perception relative to neurotypical (NT) individuals. We investigated whether this may be partly due to individual differences in cognitive abilities by comparing their performance on various pitch perception tasks on a large sample (n = 164) of autistic and NT children and adults. Our findings revealed that: (i) autistic individuals either showed similar or worse performance than NT individuals on the pitch tasks; (ii) cognitive abilities were associated with some pitch task performance; and (iii) cognitive abilities modulated the relationship between autism diagnosis and pitch perception on some tasks. Our findings highlight the importance of taking an individual differences approach to understand the strengths and weaknesses of pitch processing in autism.


A cytogenetic and endocrinologic study of a set of monozygotic isokaryotic 45,X/46,XY twins discordant for phenotypic sex: mosaicism versus chimerism.
Newborn monozygotic twins with phenotypic sexual discordance were diagnosed with 45,X/46,XY gonadal dysgenesis. Cytogenetic studies of peripheral blood (serial), skin, and gonad were performed. Serial comparative gonadotropin data and luteinizing hormone-releasing hormone stimulation tests were obtained. A phenotypically normal male twin was found to have a significant number of 45,X cells only in lymphocytes and was considered endocrinologically intact. The sexually ambiguous twin sister demonstrated a significant number of 45,X cell lines in all tissues and was considered endocrinologically agonadal. These data demonstrate the role of the 45,X karyotype on abnormal gonadal formation and function and make possible different etiologies for the 45,X cell line in both twins. While mosaicism is likely for both, chimerism is possible for the normal male.


Systematic Review of Easy-to-Learn Behavioral Interventions for Dietary Changes Among Young Adults.
Improving the diet quality of young adults may support chronic disease prevention. The approaches used and efficacy of promoting small dietary behavior changes through easy-to-learn (ETL) interventions (requiring no more than 1 hour to teach the behavior) among young adults have not yet been systematically reviewed. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 2 independent electronic searches across 6 databases were conducted to identify any articles describing ETL interventions among young adults (aged 18-35 years) and reporting dietary intake outcomes. Among 9,538 articles identified, 9 studies met eligibility criteria. Five studies reported significant improvement in the selected dietary outcome. Of these, 3 studies used an implementation intentions approach, in which participants were given or asked to write out a simple dietary behavior directive and carry it on their person. Less than half of included studies were rated as positive for overall quality. The available evidence suggests that ETL interventions targeting the dietary behaviors of young adults may be effective in improving dietary intake. Limitations of included studies were lack of follow-up after the intervention period and low generalizability. Further dietary intervention studies targeting young adults should systematically evaluate the efficacy of ETL intervention approaches among diverse samples.


The polymorphism of the complement genes in HLA.
Genes coding for the complement proteins C2, C4A, C4B and factor B lie between HLA-D and HLA-B in HLA, the major histocompatibility complex in man. All the complement components are polymorphic, particularly C4, which has many alleles at each locus. The genetic complexity of C4 extends to the number of loci each of which may be deleted or duplicated on the chromosome. The different forms of C4 showed markedly different reactivities with small molecules and on haemolytic activity in the complement system. Surprisingly, amino acid sequences of the several allelic forms of C4 appear to be very similar, with less than 1% of residue positions being changed between alleles of C4A and C4B. These results may be relevant to the increased susceptibility to autoimmune disease which is associated with particular haplotypes of the HLA complex.


PECULIARITIES OF THE CLINICAL COURSE OF NON-ALCOHOLIC STEATOHEPATITIS AGAINST THE BACKGROUND OF THE CHRONIC KIDNEY DISEASE OF THE I-III STAGE WITH SECONDARY ARTERIAL HYPERTENSION.
The article addresses the theoretical generalization of the clinical study of non-alcoholic steatohepatitis peculiarities in comorbidity with obesity and chronic kidney disease of the І-ІІІ stage, characterized by higher frequency and intensity of clinical and biochemical syndromes, the manifestation of which is likely to increase the occurrence of secondary arterial hypertension (portal hypertension syndromes, cholestasis, mesenchymal inflammation). Comorbid course of non-alcoholic steatohepatitis with chronic kidney disease is characterized by higher degree of liver steatosis compared to the patients with only non-alcoholic steatohepatitis (p<0.05), and a higher diagnostic threshold of the hepatorenal index values, which correlates with the Steato-test index (p<0.001) with strong interdependence.


Quality control for estrogen receptor quantification by dextran-coated charcoal assay: a single laboratory's experience.
Wide fluctuations in results obtained by different laboratories for the content of estrogen receptors from a single source of tissue powder were reported by several investigators at the 1979 NCI Consensus Committee Meeting for Steroid Receptors in Breast Cancer and were further supported by data collected by our laboratory for the Eastern Cooperative Oncology Group. In a multilab study the inconsistency in the receptor content is a product of the variations associated with the assay procedures used by different laboratories and those due to unavoidable daily changes in the experimental conditions within each laboratory. In this report we present data on the variation of estrogen receptor measurements obtained by a single laboratory for any single source of tissue powder repeatedly analyzed. A retrospective analysis of the data collected on the receptor content of several different batches of calf uteri analyzed on different days (inter-assay variation) under uniform conditions revealed a coefficient of variation averaging +/- 35% (standard deviation divided by mean X 100). Experiments showed that the fluctuations in the receptor yield from aliquots of the same tissue powder are primarily an effect of the homogenization step that precedes cytosol preparation. Therefore, for establishing quality control, distribution of lyophilized cytosols should precede lyophilized powders to test the efficiency of performance of laboratories. A homogenizer designed to minimize thermal denaturation is also essential.


Online control of the twin-column countercurrent solvent gradient process for biochromatography.
A new control concept for the twin-column MCSGP process has been developed. The controller is based on two independent PID controllers each of which affects one side of the product collection window. Accordingly, the two controllers, although independent, can together shift the product collection along the elution chromatogram. The product stream collected during one entire process cycle is analyzed with an at-line HPLC allowing a direct feedback of the measured purity values to the controller. The two set points are given by the purity values with respect to weak and strong impurities in the product stream. The controller performance was tested with two systems: In the first one, a three component protein model mixture was considered. The controller stability and reliability was tested in conditions of both set point tracking and rejection of feed composition and pump flow rate disturbances. The complete experiment ran for 112h during which the desired purity values were always kept within the set points. A more realistic example was the purification of a monoclonal antibody supernatant from fragments and aggregates. In this case, the process reached specifications after five cycles, and kept them for 20h of operation in spite of ongoing disturbances in pump flow rates and feed composition. A new general start-up procedure was developed and tested in this particular purification process. The procedure starts from very simple initial conditions and let the controller to identify conditions, particularly for the recycle streams, which lead to yield and purity values significantly better than the corresponding values achieved in batch chromatography in specs.


[Primary suturing of zone II flexor tendons (103 digits). Results and Kleinert's limitations].
One hundred and sixty-two instances of traumatic division of the flexor tendons in zone 2 occurring in 103 injured digits were studied in 88 patients with at least 6 months follow-up. Motion and sensibility studies as well as trophic evaluation were available for all patients. Sixty-eight patients underwent repair according to Kleinert's technique. Overall results in these cases showed a 58% rate of "satisfactory" results versus 34% when classic techniques had been employed (35 cases). Kleinert's technique afforded the highest percentage of "good" results (75%) when tendon division was isolated whereas the rate of "good" results dropped to 23% when the injury went through to the floor of the digital tunnel. Complications included joint stiffness due to adhesions (19%) mainly related to the magnitude of the initial trauma, fixed flexion deformities (15%) and secondary rupture of the tendon (7%). Excision of the superficial flexor tendon was invariably associated with a poor results. Secondary treatment of these lesions was disappointing. While we agree that Kleinert's operative technique be used whenever feasible, semipassive mobilization as indicated by Kleinert, should however be reserved for isolated lesions in cooperative patients treated in centers where closely supervised rehabilitation is available. Immobilization of the interphalangeal joints in flexion together with their separate passive mobilization according to the method of Duran and Strickland, may reduce the number of complications observed with Kleinert's technique in the following circumstances; severe lesions (groups 3 A, 3 B), inadequate healing, an uncooperative patient. It is of paramount importance to look for and repair concomitant nerve injuries. Inadequate nerve management alone in these circumstances can account for up to 25% of overall functional failures. When bilateral vascular lesions are present, it is essential that vascular repair of the digital arteries be performed at once. Unilateral arterial insult does not seem to significantly affect results in terms of active motility.


Identification of a progenitor cell population destined to form fracture fibrocartilage callus in Dickkopf-related protein 3-green fluorescent protein reporter mice.
Fracture healing is a complex biological process involving the proliferation of mesenchymal progenitor cells, and chondrogenic, osteogenic, and angiogenic differentiation. The mechanisms underlying the proliferation and differentiation of mesenchymal progenitor cells remain unclear. Here, we demonstrate Dickkopf-related protein 3 (Dkk3) expression in periosteal cells using Dkk3-green fluorescent protein reporter mice. We found that proliferation of mesenchymal progenitor cells began in the periosteum, involving Dkk3-positive cell proliferation near the fracture site. In addition, Dkk3 was expressed in fibrocartilage cells together with smooth muscle α-actin and Col3.6 in the early phase of fracture healing as a cell marker of fibrocartilage cells. Dkk3 was not expressed in mature chondrogenic cells or osteogenic cells. Transient expression of Dkk3 disappeared in the late phase of fracture healing, except in the superficial periosteal area of fracture callus. The Dkk3 expression pattern differed in newly formed type IV collagen positive blood vessels and the related avascular tissue. This is the first report that shows Dkk3 expression in the periosteum at a resting state and in fibrocartilage cells during the fracture healing process, which was associated with smooth muscle α-actin and Col3.6 expression in mesenchymal progenitor cells. These fluorescent mesenchymal lineage cells may be useful for future studies to better understand fracture healing.


Real-world efficacy and potential mechanism of resistance of icotinib in Asian advanced non-small cell lung cancer with EGFR uncommon mutations: A multi-center study.
The response to icotinib in advanced non-small cell lung cancers (NSCLC) with EGFR uncommon mutation (EGFRum) is unclear. Here we reported the efficacy and potential resistance mechanism of icotinib in Chinese EGFRum NSCLC patients. Between July 2013 and November 2016, 3117 NSCLC patients were screened for EGFRum in a multi-center study in China. Circulating tumor DNA (ctDNA) was detected and analyzed using next-generation sequencing (NGS) after progression from icotinib. The efficacy, safety and the potential resistance mechanism of icotinib were explored. After a median follow-up of 6.2 months, 69 patients (70.41%) developed disease progression, the objective rate (ORR) and disease control rate (DCR) were 13.27% and 29.59% respectively, and the median progression-free survival (PFS) was 5.5 months (95% CI: 1.2-13.0 months). Both complex-pattern with EGFR classical mutations (EGFRcm) and single-pattern have better PFS than complex-pattern without EGFRcm (median PFS was 7.2 (95% CI: 4.65-9.75), 5.2 (95% CI: 3.24-7.16) and 3.2 (95% CI: 2.97-3.44) months, respectively, P < .05); patients harboring S768I mutation had the worst PFS than others (2.0 months, P < .05). Diarrhea was the most frequent side effect (42.9%). Forty-eight (69.6%) patients developed drug resistance after 3.0 months and 81.2% of them acquired T790M mutation. Better response was observed in complex-pattern with the EGFRcm group. S768I mutation carriers may not benefit from icotinib. Acquired T790M mutation was common in icotinib-resistant EGFRum NSCLC patients.


Overview of a public health approach to pediatric hearing impairment in the Pacific Islands.
Childhood hearing impairment is a significant cause of disability in developing countries. Otitis media and meningitis are leading infectious causes of preventable hearing loss in children. It is estimated that the Pacific Islands have among the greatest global burden of childhood hearing impairment due to infectious causes, and yet there is currently very little in the research literature on pediatric hearing disorders in this region. (1) To review existing research literature on pediatric hearing impairment in the Pacific Islands, and (2) to present a public health approach to the development and improvement of childhood hearing services in the Pacific Islands. The primary tool was a comprehensive literature review. MEDLINE and ScienceDirect databases were searched for relevant journal articles. There was no limit on the date of publication. Any article reporting on hearing impairment in the Pacific Region was included. A total of 23 journal articles were found that satisfied the above inclusion criteria. The limited information available in the literature suggests that otitis media and vaccine-preventable infections are a significant cause of avoidable childhood hearing impairment in the Pacific Islands. Pediatric audiology services are limited in this region. Further research is required to develop effective public health programs that should reduce the burden of preventable childhood hearing loss in the Pacific Islands. There is limited information in the research literature on pediatric hearing impairment and audiology services in the Pacific Islands. Epidemiological data based on the WHO Ear and Hearing Disorders Survey Protocol are urgently needed, and the development of audiology services within the existing public and primary health care framework should reduce the burden of preventable hearing loss in the Pacific Islands.


Management of choledocholithiasis in the elderly: Same-admission cholecystectomy remains the standard of care.
Current guidelines recommend that patients with choledocholithiasis undergo same-admission cholecystectomy. The compliance with this guideline is poor in elderly patients. We hypothesized that elderly patients treated with endoscopic retrograde cholangiopancreatography (ERCP) alone would have higher complication and readmission rates than the patients treated with cholecystectomy. The Nationwide Readmissions Database was queried for all patients aged ≥65 years with admission for choledocholithiasis January to June 2016. The patients were divided based on index treatment received: (1) no intervention; (2) ERCP alone; or (3) cholecystectomy. Multivariate analyses identified predictors of cholecystectomy during index admission and of readmissions. A total of 16,121 patients with choledocholithiasis were admitted; 38.4% underwent cholecystectomy, 37.6% endoscopic retrograde cholangiopancreatography alone, and 24.0% no intervention. The patients not receiving a cholecystectomy were more likely to be older, female, have a higher Elixhauser score, do-not-resuscitate status, and at a teaching hospital (all P < .001). Emergency readmissions for recurrent biliary disease were lowest in patients undoing a cholecystectomy (2.2% vs 9.2% endoscopic retrograde cholangiopancreatography and 12.4% no intervention, P < .001), as were readmissions for complications (3.6% vs 5.5% and 7.8%, P < .001). Cholecystectomy reduced rates of readmissions for recurrent disease (odds ratio 0.168, P < .001), for complications (odds ratio 0.540, P < .001), and death during readmission (odds ratio 0.503, P = .007); endoscopic retrograde cholangiopancreatography alone reduced only rates of readmissions. Age was not a predictor of readmission or death. Index admission cholecystectomy is associated with a lower risk of readmission for biliary disease or complications, as well as death during readmission, in elderly patients. Age alone is not predictive of outcomes; surgical intervention should be guided by clinical condition, comorbidities, and patient preference.


[Transition of differences between men and women about awareness of stress during the recent two decades: data from comparison of questionnaires at two different eras].
Stress is one of the important factors on lifestyle diseases such as type 2 diabetes. Recent great changes of female roles in social activities and the introduction of Japanese public nursing care insurance in 2000 might lead to some changes in the household roles, which would have a big impact on the differences in stress between men and women. I herein investigated the two questionnaires about the awareness of stress in daily lives in 273 persons conducted in 1993 before the beginning of public nursing care insurance and in 590 persons in 2010 after the program was implemented. The understanding of the results and re-thinking of so-called 'traditional sexual roles' will provide helpful clues to the precise solution for coping with stress.


Antidiuretic hormone infusion reduces taurine and NaCl-induced hypernatremia in the rat.
Rats drinking taurine and hypertonic saline (T + S) develop severe hypernatremia, but rats drinking either T or S alone do not. One hypothesis for this disruption of homeostasis is that the T + S combination interferes with the actions of antidiuretic hormone (ADH). Rats drinking T + S developed severe hypernatremia (170 mmol/L) by day 8 when infused with distilled water by osmotic minipumps, but maintained plasma sodium below 150 mmol/L when infused with ADH. Cumulative water balance in T + S drinkers receiving ADH was consistently higher than in those not receiving ADH. However the ratio of cumulative sodium balance to cumulative water balance suggests little uniform advantage to rats receiving ADH nor does comparison of urine osmolality in the two groups. Precisely how ADH administration reduces hypernatremia in T + S drinking rats remains unclear, but the hypothesis that T + S interferes with the action of ADH in its regulation of extracellular fluid volume and osmolality remains viable.