Release of DNA into the medium by competent Streptococcus pneumoniae: kinetics, mechanism and stability of the liberated DNA.
The release of chromosomal DNA into culture media has been reported for several naturally transformable bacterial species, but a direct link between competence development and the liberation of DNA is generally lacking. Based on the analysis of strains with mutations in competence-regulatory genes and the use of conditions favouring or preventing competence, we provide evidence that DNA release is triggered by the induction of competence in Streptococcus pneumoniae. Kinetic analyses revealed that whereas competence was maximal 20 min after addition of competence-stimulating peptide, and then decreased, the amount of liberated DNA continued to increase and reached a maximum in stationary phase, when cells are no longer competent for DNA uptake. These data are not consistent with the proposal that release of DNA by a fraction of the population is coordinated with uptake by the remainder. Moreover, we observed that an unidentified DNase was specifically induced or released in competent cultures, and that together with the major pneumococcal endonuclease, EndA, it could degrade released DNA. Nearby complete abolition of release in a mutant lacking both the major autolysin, LytA, and the autolytic lysozyme, LytC, indicated that DNA liberation occurs by LytA-LytC-dependent cell lysis. These observations suggest that competence-dependent DNA release is one facet of a more general phenomenon of sensitization to autolysis that reaches its maximum in stationary phase.


A Transcriptomics-Based Meta-Analysis Combined With Machine Learning Identifies a Secretory Biomarker Panel for Diagnosis of Pancreatic Adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is generally incurable due to the late diagnosis and absence of markers that are concordant with expression in several sample sources (i.e., tissue, blood, plasma) and platforms (i.e., Microarray, sequencing). We optimized meta-analysis of 19 PDAC (tissue and blood) transcriptome studies from multiple platforms. The key biomarkers for PDAC diagnosis with secretory potential were identified and validated in different cohorts. Machine learning approach i.e., support vector machine supported by leave-one-out cross-validation was used to build and test the classifier. We identified a 9-gene panel (IFI27, ITGB5, CTSD, EFNA4, GGH, PLBD1, HTATIP2, IL1R2, CTSA) that achieved ∼0.92 average sensitivity and ∼0.90 average specificity in distinguishing PDAC from healthy samples in five training sets using cross-validation. These markers were also validated in proteomics and single-cell transcriptomics studies suggesting their prognostic role in the diagnosis of PDAC. Our 9-gene classifier can not only clearly discriminate between better and poor survivors but can also precisely discriminate PDAC from chronic pancreatitis (AUC = 0.95), early stages of progression [Stage I and II (AUC = 0.82), IPMA and IPMN (AUC = 1), and IPMC (AUC = 0.81)]. The 9-gene marker outperformed the previously known markers in blood studies particularly (AUC = 0.84). The discrimination of PDAC from early precursor lesions in non-malignant tissue (AUC > 0.81) and peripheral blood (AUC > 0.80) may assist in an early diagnosis of PDAC in blood samples and thus will also facilitate risk stratification upon validation in clinical trials.


Tumor Diameter is an Easy and Useful Predictor of Recurrence in Stage II Colorectal Cancer.
Adjuvant chemotherapy for stage II colorectal cancer (CRC) can generally be administered to high-risk subgroups. To better identify these patients, we aimed at assessing factors that affect recurrence. In our hospital, 432 colon and 96 rectal stage II cancer patients who underwent surgical resection between 2001 and 2011 were divided into recurrence and non-recurrence groups. Age, sex, lymphatic vessel invasion, venous invasion, tumor diameter, tumor depth, histological type, preoperative carcinoembryonic antigen level, number of sampled nodes, adjuvant chemotherapy, morphology, surgical approach, anastomotic leakage, preoperative bowel obstruction, and preoperative perforation were retrospectively compared between the groups. For colon cancer, multivariate analysis revealed a significant association between tumor diameter ≥40 mm and recurrence (p = 0.039). For rectal cancer, multivariate analysis revealed that tumor diameter ≥50 mm (p = 0.001) and ≤12 sampled nodes (p = 0.021) were associated with recurrence. Tumor diameter in rectal cancer was associated with worse disease-free survival (p = 0.026). Tumor diameter is a significant predictor of recurrence in stage II CRC. This is an important finding because tumor diameter is easy to evaluate clinically and might help to identify candidates for adjuvant chemotherapy.


Tics secondary to craniocerebral trauma.
We describe three adult patients who presented with multifocal motor and vocal tics secondary to craniocerebral trauma. In one case, the tics were accompanied by marked obsessive-compulsive behavior. All patients were involved in motor vehicle accidents resulting in closed craniocerebral trauma. The latency of onset between head trauma and the movement disorder varied between 1 day and a few months. Magnetic resonance imaging, which was performed in all three patients, did not detect any structural lesions of the basal ganglia or the brainstem. Extensive bifrontal leukoencephalopathy was found in one patient who suffered severe head trauma.


Danger of false negative (exclusion) or false positive (diagnosis) for 'congenital thrombophilia' in the age of anticoagulants.
Background Most guidelines and experts recommend against performance of thrombophilia testing in general, and specifically against testing patients on pharmacological anticoagulants, due to substantially increased risk of false positive identification. For example, vitamin K antagonist (VKA) therapy affects protein C (PC) and protein S (PS), as well as some clotting assays (e.g. as used to investigate activated PC resistance [APCR]). Although heparin may also affect clotting assays, most commercial methods contain neutralisers to make them 'insensitive' to therapeutic levels. Direct oral anticoagulants (DOACs) also affect a wide variety of thrombophilia assays, although most reported data has employed artificial in vitro spiked samples. Methods In the current report, data from our facility for the past 2.5 years has been assessed for all 'congenital thrombophilia' related tests, as evaluated against patient anticoagulant status. We processed 10,571 'thrombophilia' related test requests, including antithrombin (AT; n=3470), PC (n=3569), PS (n=3585), APCR (n=2359), factor V Leiden (FVL; n=2659), and prothrombin gene mutation (PGM; n=2103). Results As expected, VKA therapy affected PC and PS, and despite manufacturer claims, also APCR. Most assays, as suggested by manufacturers, were largely resistant to heparin therapy. DOACs' use was associated with falsely low APCR ratios (i.e. FVL-like effect) and somewhat unexpectedly, anti-Xa agents apixaban and rivaroxaban were also associated with lower AT and higher PS values. Conclusions It is concluded that ex-vivo data appears to confirm the potential for both false positive and false negative 'thrombophilia' events in patients on anticoagulant (including DOAC) treatment.


Factors influencing use of home care and nursing homes.
This paper reports a study comparing the characteristics of patients who use home care services and those who are cared for in nursing homes, and identifying the factors that influence the use of these care settings. The increase in the functionally dependent older population has led to an increase in the number of nursing homes and home care agencies. It has become clear that, rather than disputing which is the better of these options, it would be better to determine the characteristics of patients who use the two long-term care services. Gaining an understanding of the unique characteristics of patients who are cared for by home care agencies and those who are cared for in nursing homes will be imperative for reforming and developing long-term care systems. The research model was based on the Anderson Model of Health Services Utilization. Interviews were conducted with 99 stroke survivors from two home care agencies and four nursing homes, and their family members, between May and December 2001. The patient characteristics that predicted greater use of home care rather than nursing home services were: being married, poor physical function, impaired cognitive function, higher rates of comorbidity, various medical complications, and/or number of catheters (e.g. urinary catheter, naso-gastric tube). Contrary to the findings of previous studies conducted in countries with ageing populations, our findings indicate that in South Korea home care agencies, rather than nursing homes, provide care for severely impaired patients. This may be due to differences between countries in their long-term care systems and cultural attitudes toward end-of-life care. Our results will contribute to the development or reformation of long-term care systems in countries with ageing populations, and to the development of strategies for increasing access to these services.


Amino acid residues critical for endoplasmic reticulum export and trafficking of platelet-activating factor receptor.
Several residues are conserved in the transmembrane domains (TMs) of G-protein coupled receptors. Here we demonstrate that a conserved proline, Pro(247), in TM6 of platelet-activating factor receptor (PAFR) is required for endoplasmic reticulum (ER) export and trafficking after agonist-induced internalization. Alanine-substituted mutants of the conserved residues of PAFRs, including P247A, were retained in the ER. Because a PAFR antagonist, Y-24180, acted as a pharmacological chaperone to rescue ER retention, this retention is due to misfolding of PAFR. Methylcarbamyl (mc)-PAF, a PAFR agonist, did not increase the cell surface expression of P247A, even though another ER-retained mutant, D63A, was effectively trafficked. Signaling and accumulation of the receptors in the early endosomes were observed in the mc-PAF-treated P247A-expressing cells, suggesting that P247A was trafficked to the cell surface by mc-PAF, and thereafter disappeared from the surface due to aberrant trafficking, e.g. enhanced internalization, deficiency in recycling, and/or accelerated degradation. The aberrant trafficking was confirmed with a sortase-A-mediated method for labeling cell surface proteins. These results demonstrate that the conserved proline in TM6 is crucial for intracellular trafficking of PAFR.


Influence of Ozone on the Stable Carbon Isotope Composition, deltaC, of Leaves and Grain of Spring Wheat (Triticum aestivum L.).
The relative composition of stable carbon isotopes, delta(13)C, was determined in flag leaves and grain of spring wheat (Triticum aestivum L. cv Albis) grown in open-top field fumigation chambers and exposed to different O(3) levels during the growing season. The aim of the study was to establish exposure-response relationships for the radiation-weighted seasonal mean O(3) concentration and delta(13)C (relative deviation of the (13)C/(12)C ratio) values of the two plant parts. Samples were collected at harvest in 1986, 1987, and 1988. With increasing O(3) concentration, delta(13)C values increased (became less negative) proportionally. Year to year delta(13)C differences at equivalent O(3) concentrations were small. The shift in delta(13)C caused by O(3) was more pronounced in grain than in leaves. According to models of (13)C discrimination in C(3) plants, these results indicate increasing limitation of photosynthesis by CO(2) diffusion relative to limitation by carboxylation with increasing O(3) exposure. This conclusion is not in agreement with results from gas exchange analysis. Water use efficiency in green flag leaves tended to decrease with increasing O(3), indicating a dominating effect of O(3) on CO(2) carboxylation.


Tracking by third-order tensor representation.
This paper proposes a robust tracking algorithm by third-order tensor representation and adaptive appearance modeling. In this method, the target in each video frame is represented by a third-order tensor. This representation preserves the spatial correlation inside the target region and can integrate multiple appearance cues for target description. Based on this representation, a multilinear subspace is learned online to model the target appearance variations during tracking. Compared to other methods, our approach can detect local spatial structure in the target tensor space and fuse information from different feature spaces. Therefore, the learned appearance model is more discriminative when there are significant appearance variations of the target or when the background gets cluttered. Applying the multilinear algebra, our appearance model can efficiently be learned and updated online, without causing high-dimensional data-learning problems. Then, tracking is implemented in the Bayesian inference framework, where a likelihood model is defined to measure the similarity between a test sample and the learned appearance model, and a particle filter is used to recursively estimate the target state over time. Theoretic analysis and experiments compared with other state-of-the-art methods demonstrate the effectiveness of the proposed approach.


Concurrent Occurrence of Primary Biliary Cirrhosis and Rheumatoid Arthritis.
Primary biliary cirrhosis (PBC) is an autoimmune cholestatic disorder of the liver. A diagnostic serum marker for PBC is an anti-mitochondrial antibody. Most prominent histologic findings of PBC are portal inflammation and destruction of interlobular bile ducts. The PBC occurs only in 40 to 400 individuals per million in the general population. About 1.8 - 5.6% of individuals with this rare disorder have rheumatoid arthritis (RA). This case report describes a 56-year-old female with concurrent rheumatoid arthritis and primary biliary cirrhosis. The patients with RA are at higher risk of developing PBC compared to the general population. Thus, abnormal liver function test in the patients with RA, especially in the absence of alternative cause, warrants thorough investigation for PBC. Early diagnosis and treatment will improve the outcome of patients who develop PBC.


Granulocytes enhance LPS-induced tissue factor activity in monocytes via an interaction with platelets.
In the present study we have investigated the effect of platelets and granulocytes on bacterial lipopolysaccharide (LPS)-induced tissue factor (TF) activity in monocytes. Experiments were performed on freshly isolated cells resuspended in heparinized plasma and recombined with platelet-poor or platelet-rich plasma. In a platelet-dependent reaction the granulocytes enhanced LPS-induced TF activity by an average of 100%. The effect was dose dependent with regard to the number of both granulocytes and platelets, respectively. Granulocytes and/or platelets did not affect LPS-induced tumor necrosis factor (TNF) secretion from monocytes. Phorbol myristate acetate (PMA) per se was not able to induce TF activity in our system. In contrast, the agonist caused a substantial increase in TF activity induced by LPS. The effect was totally dependent on the presence of platelets and was shown to be due to stimulation of both granulocytes and monocytes (the activity rose from 30 +/- 7 to 83 +/- 12 mU/10(6) cells in the presence of platelets and from 69 +/- 8 to 143 +/- 22 mU/10(6) cells in the presence of platelets and granulocytes). Effects similar to those observed with PMA were obtained with physiological concentrations (10 ng/ml) of TNF. A combination of these two agonists gave no further amplification of LPS-induced TF activity compared with the effect of the agonists separately. Low concentrations of a monoclonal anti-CD15 antibody abolished the stimulatory effects of platelets and granulocytes. Furthermore, the anti-CD15 antibody neutralized the effect of TNF, whereas the PMA effect was reduced by almost 75%. These results were confirmed in a whole-blood system. The inhibitory effect of the antibody may be associated with CD15's role as a complementary ligand for PADGEM. Our study indicates that a close interaction between granulocytes, platelets, and monocytes is essential for optimal TF activity induced by LPS. It is hypothesized that the effect of granulocytes is related to their ability to activate platelets. We propose that upon activation granulocytes secrete a product that enhances the capacity of platelets to stimulate TF activity in monocytes.


Lichen planus-like lesions caused by penicillamine in primary biliary cirrhosis.
Six patients with primary biliary cirrhosis experienced lichen planus-like lesions while taking penicillamine. Oral lesions developed in all patients, and the lichenoid lesions also appeared elsewhere in two patients. Lichen planus-like lesions developed from four to 16 months after penicillamine therapy had been started, and, in four cases, they resolved in one to three months after use of the drug was stopped. Two patients have continued using penicillamine despite adverse cutaneous and mucosal reactions and have continued to experience lichen planus-like lesions intermittently. Other cutaneous reactions associated with penicillamine are reviewed.


[Atrial fibrillation in the elderly].
Elderly people more than 70 years develop atrial fibrillation that causes stroke and heart failure. Furthermore, the elderly people who have atrial fibrillation accompany many risk factor, and develop cerebral infarction easily. Therefore, it is very important to prevent cerebral infarction using anticoagulant drugs. So far we usually use warfarin, which has many limitations, especially cerebral bleeding. Now new anticoagulant drugs(dabigatran and rivaroxaban) can become available. Therefore, we have to learn how to use those drugs. They have to carefully be used because they discharge from kidney and old aged patients have potential renal dysfunction. We mainly explain anticoagulant therapy in old aged patients.


Ustekinumab in chronic immune-mediated diseases: a review of long term safety and patient improvement.
Ustekinumab is a fully human monoclonal antibody targeting the common p40 subunit shared by interleukin (IL)-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 with their cell surface receptors, and thus blocks T helper (Th)-1 IL-12 and Th-17 IL-23 inflammatory pathways. Ustekinumab has been evaluated in the treatment of various chronic immune-mediated diseases including, psoriasis, psoriatic arthritis, Crohn's disease, and multiple sclerosis. It led to a rapid and durable improvement in psoriasis area and severity index in patients with moderate to severe psoriasis. Ustekinumab also improved joint symptoms of psoriatic arthritis. Results in Crohn's disease were more mitigated, albeit with a symptomatic improvement in patients refractory to tumor necrosis factor-α inhibitors. Ustekinumab did not reduce the number of magnetic resonance imaging brain lesions in multiple sclerosis. The most common adverse events to have been observed during clinical trials are mild in intensity, and include respiratory tract infections, nasopharyngitis, headaches, and injection site reactions. A pooled analysis of clinical trial data indicated no specific patterns of infection or malignancy under long-term ustekinumab administration. Ustekinumab is easy to use, has a comfortable therapeutic regimen, improves quality of life in patients, and thus appears to be an attractive biological treatment that is adapted and accepted by patients with moderate to severe psoriasis.


Synthetic augmentation in massive rotator cuff tears.
Massive rotator cuff tears represent a great challenge in orthopaedic. They are associated with persistent defects, weakness, and poor outcomes and can cause an uncoupling of forces across the glenohumeral joint, with unstable shoulder kinematics. In the last few years, a notable interest has emerged to develop new treatment strategies that provide effective mechanical reinforcement of rotator cuff repair and stimulate and enhance the patient's intrinsic healing potential. Tissue engineering techniques using novel scaffold materials offer potential alternatives for managing massive irreparable rotator cuff tears. Synthetic scaffolds, manufactured from chemical compounds, have gained much interest to bridge massive rotator cuff tears. Preliminary studies support the idea that synthetic scaffolds can provide an alternative for rotator cuff augmentation with an enormous therapeutic potential. Despite the growing clinical use of synthetic scaffold devices for rotator cuff repair, there are numerous questions related to their indication, surgical application, safety, mechanism of action, and efficacy that remain to be clarified or addressed. We review the current basic science and clinical understanding of synthetic scaffolds for massive rotator cuff repair, reporting the preclinical and clinical studies carried out to date in this field. We underline the benefits and limitations of the available synthetic scaffolds for augmentation of rotator cuff tears, and discuss the implications of these literature data on the future directions for the use of these scaffolds in tendon repair procedures.


Concentrations of abscisic Acid and indoleacetic Acid in cotton fruits and their abscission zones in relation to fruit retention.
An experiment was conducted with field-grown cotton (Gossypium hirsutum L.) to determine the effects of drought and an increase in available photosynthate on the abscisic acid (ABA) and indoleacetic acid (IAA) contents of 3-day-old bolls and their abscission zones. Photosynthate availability was manipulated by removing about two-thirds of the plants to permit increased irradiance, and thus photosynthesis, in the plant canopy. The demand for photosynthate was decreased by removing all bolls from the remaining plants. The thinning and defruiting operations were performed about 3 weeks after first flower. Control plants were neither thinned nor defruited. Effects of water deficit were observed by making three harvests at different times during a 2-week irrigation cycle. Increasing the availability of photosynthate increased boll retention, but had relatively little effect on the concentrations of ABA and IAA in bolls. However, it did increase the concentration of IAA in abscission zones. Water deficit increased the ABA content of bolls and abscission zones and decreased the IAA content of bolls and abscission zones. Across all treatments, the IAA content of abscission zones was positively correlated, and the ABA content of bolls was negatively correlated, with boll retention. The results indicate that stresses change the hormonal balance in ways that are consistent with observed increases in fruit abscission.


An Exercise Intervention for South Asian Mothers with Risk Factors for Diabetes.
South Asians (Indians, Pakistanis, Bangladeshis, Sri Lankans, Nepalis, and Bhutanese) in the United States have a very high prevalence of type 2 diabetes mellitus (DM). This pilot study evaluated a culturally-tailored exercise intervention among South Asian immigrant mothers with DM risk factors. Through an academic-community partnership, South Asian women with risk factors for DM and who had at least one child between 6-14 years were enrolled into this single-arm study. The intervention for the mothers included 16-weeks of twice weekly exercise classes, self-monitoring with activity trackers, goal-setting, and classes on healthy eating. Based on prior community-based participatory research, children were offered exercise classes during the mothers' classes. The primary efficacy outcomes were change in mothers' moderate/vigorous physical activity and body weight pre- and post-intervention (16-weeks). Program adherence, clinical, and psychosocial outcomes were measured. A qualitative process evaluation was conducted to understand participant perspectives. Participants' (n=30) average age was 40 (SD=5) years., 57% had a high school education or less, and all were overweight/obese.. At baseline, women were not meeting recommended physical activity guidelines. Overall, participants attended 75% of exercise classes. Compared to baseline, participants' weight decreased by 3.2 lbs. (95% CI: -5.5, -1.0) post-intervention. Among women who attended at least 80% of classes (n=17), weight change was -4.8 lbs, (95% CI: -7.7, -1.9). Change in accelerometer-measured physical activity was not significant; however exercise-related confidence increased from baseline (p-value <0.01). Women described multiple physical and psychosocial benefits from the intervention. This pilot study suggests that a culturally-tailored exercise intervention that included exercise classes for children was feasible and had physical and psychosocial benefits in South Asian mothers with risk factors for DM.


Current sterilization and packaging methods for polyethylene.
Gamma sterilization in an air environment can induce oxidation in polyethylene. Oxidation can lead to polyethylene embrittlement, compromising mechanical integrity and clinical performance of polyethylene bearings. For these reasons, orthopaedic manufacturers have modified their methods of sterilizing and packaging polyethylene. Two alternative approaches have emerged: sterilization by non-radiation methods and sterilization by gamma irradiation in inert environments. The current study presents a prognosis for clinical performance of polyethylene sterilized with new methods, based on material property analyses (oxidation levels, mechanical properties, crosslink density) of never implanted and retrieved bearings. Data from bearings that were never implanted which were sterilized with the new methods and shelf aged as many as 3 years, show negligible oxidation, ductility above 400%, and ultimate tensile strength near 50 MPa, all exceeding specifications of the American Society for Testing and Materials. There are significant differences in crosslink density (swell ratio) depending on the sterilization method. Retrievals indicate that bearings sterilized with these new methods are performing well clinically and that the majority are not changing with time. The current study suggests that the shelf oxidation problem has been addressed by these new sterilization techniques and that clinical performance at short followup is acceptable. However, long-term clinical performance must be evaluated in the future.


The psychological characteristics of patients suffering from anorexia nervosa and the nurse's role in creating a therapeutic relationship.
This paper reviews research on the psychological characteristics of patients suffering from anorexia nervosa and that examining the therapeutic relationship. The former research suggests that anorexic patients possess a psychological profile characterized by: a phobia of weight gain and fear of loss of control; alexithymia and lack of introceptive awareness; mistrust of self and others; cognitive dysfunction; low self-esteem; and often the presence of starvation-induced depression. The latter strongly suggests that in order for a relationship to be therapeutic it needs to be characterized by: empathy; positive regard and acceptance; warmth; commitment; trust; genuineness; and be non-judgemental. The implications of these research findings regarding the nurse's role in forming a therapeutic relationship with anorexic patients is then discussed. It is seen that it is vital that nurses receive adequate education before working with such patients, and that their knowledge is regularly updated. Nurses should receive regular clinical supervision and support, in order to ensure that they are able to provide therapeutic care for such patients.


True hermaphrodite: very unusual type.
True hermaphrodite is one of the rare gonadal as well as genital abnormality due to a defect in sexual differentiation. Here, we are reporting the most unusual type of true hermaphrodite diagnosed at the age of 25 years during operation for undescended testis, presenting as a case of infertility and failure to ejaculate during sexual intercourse. The patient was found to have grossly as well as histologically proven left ovary, left fallopian tube and uterus as well as a well descended left testis, with totally absent either right fallopian tube and ovary or testis. Thus, this is unusual finding to ratify the occurrence of true hermaphrodite in the absence of ambiguous external genitalia.


The importance of surgery to non-small cell carcinoma of lung with mediastinal lymph node metastasis.
In the past 25 years, 1,654 patients with non-small cell cancer underwent resection at National Cancer Center Hospital, Tokyo. A comparative study has been made of 5-year survival of patients who had pulmonary resection with and without mediastinal lymph node dissection. There were 426 patients (25.8% of the total) with N2 M0 disease. Of these, 345 underwent pulmonary resection with mediastinal lymph node dissection. The 5-year survival in this group was 15.9% (T1 N2 M0, 30.0%; T2 N2 M0, 14.5%; and T3 N2 M0, 12.9%). In the remaining 81 patients, who did not have mediastinal lymph node dissection, 5-year survival was 6.7%. Of the 426 patients with N2 M0 disease, 242 were select patients who underwent a curative operation with an overall 5-year survival of 19.2%. Sixty-six of them had squamous cell carcinoma and a 5-year survival of 30.8%; 153 had adenocarcinoma and a survival of 16.0%; 14 had large cell carcinoma and a survival of 12.8%; and 9 had adenosquamous cell carcinoma, and none survived 5 years. To improve the end results, it is important to perform as many curative operations with mediastinal lymph node dissection as possible. Histological cell type and tumor status must be taken into consideration.


Five surgical maneuvers on nasal mucosa movement in cleft palate repair: A cadaver study.
This biomechanical study aims to characterize the nasal mucosa during palatoplasty, thereby describing the soft tissue attachments at different zones and quantifying movement following their release. Palatal nasal mucosa was exposed and divided in the midline in 10 adult cadaver heads. Five consecutive maneuvers were performed: (1) elevation of nasal mucosa off the maxilla, (2) dissection of nasal mucosa from soft palate musculature, (3) separation of nasal mucosa from palatine aponeurosis, (4) release of mucosa at the pterygopalatine junction, and (5) mobilization of vomer flaps. The mucosal movements across the midline at the midpalate (MP) and posterior nasal spine (PNS) following each maneuver were measured. At the MP, maneuvers 1-4 cumulatively provided 3.8 mm (36.9%), 4.9 mm (47.6%), 6.1 mm (59.2%), and 10.3 mm, respectively. Vomer flap (10.5 mm) elevation led to mobility equivalent to that of maneuvers 1-4 (p = 0.72). At the PNS, cumulative measurements after maneuvers 1-4 were 1.3 mm (10%), 2.4 mm (18.6%), 5.7 mm (44.2%), and 12.9 mm. Here, vomer flaps (6.5 mm) provided less movement (p < 0.001). Maneuver 4 yielded the greatest amount of movement of the lateral nasal mucosa at both MP (4.2 mm, 40.8%) and PNS (7.2 mm, 55.8%). At the MP, complete release of the lateral nasal mucosa achieves as much movement as the vomer flap. At the hard-soft palate junction, the maneuvers progressively add to the movement of the lateral nasal mucosa. The most powerful step is release of attachments along the posterior aspect of the medial pterygoid.


Cryptand-like anion receptors.
The design of supramolecular hosts for anions began with simple diaza bicycles, named katapinands, and has evolved over the last 40 years to a number of elegantly designed receptors capable of binding many different anions. About the same time the term cryptand appeared in reference to another bicyclic compound that was selective for alkaline-earth ions. Since the first report these simple bicycles, a vast arena of hosts has appeared, including acyclic, monocyclic, and other multicyclic supramolecular receptors. Studies of these systems have revealed considerable information about anion coordination chemistry, including the fact that many of these complexes mimic their transition-metal corollaries in terms of coordination numbers. However, for anions interactions occur via H-bonding most often, rather than the coordinate covalent or dative bonds observed in transition-metal coordination. This critical review examines the design of enclosed, primarily bicyclic cryptands as hosts for anions, with a small scattering of higher polyhedra when deemed appropriate to the discussion. In order to show the development (evolution) of the field, key examples of early work will be noted and compared with more recent developments (136 references).


Oligosaccharide relative quantitation using isotope tagging and normal-phase liquid chromatography/mass spectrometry.
The growing interest in the conversion of plant biomass into biofuels has recently highlighted the lack of analytical techniques that are able to profile the fine structures of plant cell-wall polysaccharides. Here we present a new liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) platform called Oligosaccharide Quantitation using Isotope Tagging (OliQuIT) developed for profiling the oligosaccharides derived from glycosyl hydrolase digestion of polysaccharides. The method is demonstrated using different arabinoxylan-derived oligosaccharide samples, which are reductively aminated with either the light (12C6) or heavy (13C6) form of aniline. The complex oligosaccharide mixtures are analysed by capillary normal-phase (NP)-LC and ESI-MS. Importantly, arabinoxylan oligosaccharide isomers are separated by NP-LC and their relative abundance in different samples can be determined from the intensities of ions labeled with the different isotopes. OliQuIT will be of use in multiple applications, including screening for plant varieties with improved saccharification properties, characterizing glycosyl hydrolase specificities and analysing plant glycosyl transferase mutants.


Region of difference 2 contributes to virulence of Mycobacterium tuberculosis.
Mycobacterium bovis BCG strains are live, attenuated vaccines generated through decades of in vitro passage. Because in vitro growth does not select for interaction with the host, it has been hypothesized that genetic loci lost from BCG code for virulence determinants that are dispensable for growth in the laboratory, as exemplified by Region of Difference 1 (RD1), which was lost during the original derivation of BCG between 1908 and 1921. Region of Difference 2 (RD2) was lost during the ongoing propagation of BCG between 1927 and 1931, a time that coincides with reports of the ongoing attenuation of the vaccine. In this study, RD2 has been disrupted in M. tuberculosis H37Rv to test whether its loss contributed to the further attenuation of BCG. The deletion of RD2 did not affect in vitro growth; in contrast, the mutant manifested a decrease in pulmonary and splenic bacterial burdens and reduced pathology in C57BL/6 mice at early time points. This attenuated phenotype was complemented by reintroducing the genes Rv1979c to Rv1982 (including mpt64) but not Rv1985c to Rv1986. In RAW 264.7 macrophages, H37Rv:ΔRD2 showed a decreased proliferation and impaired modulation of the host innate immune response; both observations were complemented with Rv1979c to Rv1982. To test the effect of RD2 disruption on innate immunity, Rag(-/-) mice were infected; H37Rv:ΔRD2 had increased survival times compared those of H37Rv. These findings support the notion that the safety profile of certain BCG vaccines stems from multiple attenuating mutations, with the RD2 deletion resulting in a less-virulent organism through the impaired bacterial manipulation of the host innate immune response.


Perioperative care of a patient with Beare-Stevenson syndrome.
Beare-Stevenson syndrome is a craniofacial syndrome consisting of a specific pattern of craniosynostosis resulting in a cloverleaf skull deformity and hydrocephalus, down-slanting palpebral fissures, proptosis, hypertelorism, strabismus, dysmorphic ears, choanal atresia, cleft palate, cutis gyratum, acanthosis nigricans, and abnormal genitalia. Its primary cause has been identified as a single amino acid substitution in fibroblast growth factor receptor 2. Of primary importance to the anesthesiologist are issues related to airway management resulting from midface hypoplasia, choanal atresia, and airway abnormalities (tracheal stenosis). Additional issues affecting airway management include associated cervical spine and foramen magnum abnormalities. The authors present their experience caring for a patient with Beare-Stevenson syndrome and discuss the anesthesia care of these patients.


Highly Luminescent Zn(x)Cd(1-x)Se/C Core/Shell Nanocrystals: Large Scale Synthesis, Structural and Cathodoluminescence Studies.
Zn(x)Cd(1-x)Se/C core/shell nanocrystals with 31-39 nm semiconducting core and 11-25 nm carbon shell were synthesized from solid state precursors in large scale amounts. A mixture of spherical and tripod nanostructures were obtained only in the one-step reaction (ZC3), where the Zn- and Cd-precursors were reacted simultaneously, rather than in the two step reactions (ZC1 and ZC2), where largely spherical nanostructures were observed. Rietveld analysis of the X-ray diffraction patterns of the samples prepared in three different ways, all under their autogenic pressure, reveal varying compositions of the Zn(x)Cd(1-x)Se nanocrystal core, where the cubic phases with higher Zn content were dominant compared to the hexagonal phases. Carbon encapsulation offers excellent protection to the nanocrystal core and is an added advantage for biological applications. Cathodoluminescence (CL) measurements with spatially integrated and highly localized excitations show distinct peaks and sharp lines at various wavelengths, representing emissions from single nanostructures possessing different compositions, phases, and sizes. Transmission electron microscopy (TEM) showed striations in the nanocrystals that are indicative of a composition modulation, and possibly reveal a phase separation and spinodal decomposition within the nanocrystals. Thermal quenching of the luminescence for both the near band-edge and defect related emissions were observed in the range 60-300 K. The measured activation energies of ∼50-70 meV were related to the presence of shallow donors or acceptors, deep level emissions, and thermal activation and quenching of the luminescence due to the thermal release of electrons from shallow donors to the conduction band or a thermal release of holes from shallow acceptors to the valence band. Spatially integrated CL spectra revealed the existence of broadening and additional components that are consistent with the presence of a composition modulation in the nanocrystals. Spatial localization of the emission in isolated single nanocrystals was studied using monochromatic CL imaging and local CL spectroscopy. CL spectra acquired by a highly localized excitation of individual nanocrystals showed energy shifts in the excitonic luminescence that are consistent with a phase separation into Zn- and Cd-rich regions. The simultaneous appearance of both structural and compositional phase separation for the synthesis of Zn(x)Cd(1-x)Se nanocrystals reveals the complexity and uniqueness of these results.


Neuraminidase-1 is required for the normal assembly of elastic fibers.
The assembly of elastic fibers in tissues that undergo repeated cycles of extension and recoil, such as the lungs and blood vessels, is dependent on the proper interaction and alignment of tropoelastin with a microfibrillar scaffold. Here, we describe in vivo histopathological effects of neuraminidase-1 (Neu1) deficiency on elastin assembly in the lungs and aorta of mice. These mice exhibited a tight-skin phenotype very similar to the Tsk mouse. Normal septation of Neu1-null mice did not occur in neonatal mice, resulting in enlarged alveoli that were maintained in adults. The abnormal development of elastic fibers was remarkable under electron microscopy and confirmed by the overlapping distribution of elastin, fibrillin-1, fibrillin-2, and fibulin-5 (Fib-5) by the light microscopy immunostainings. Fib-5 fibers appeared diffuse and unorganized around the alveolar walls and the apex of developing secondary septal crests. Fibrillin-2 deposition was also abnormal in neonatal and adult lungs. Dispersion of myofibroblasts appeared abnormal in developing lungs of Neu1-null mice, with a random distribution of myofibroblast around the alveolar walls, rather than concentrating at sites of elastin synthesis. The elastic lamellae in the aorta of the Neu1-null mice were thinner and separated by hypertrophic smooth muscle cells that were surrounded by an excess of the sialic acid-containing moieties. The concentration of elastin, as measure by desmosine levels, was significantly reduced in the aorta of Neu1-null mice. Message levels for tropoelastin and Fib-5 were normal, suggesting the elastic fiber defects in Neu1-null mice result from impaired extracellular assembly.


Freezing of water in dormant vegetative apple buds in relation to cryopreservation.
Various empirical prefreezing protocols have been used to facilitate cryopreservation of dormant buds from woody plants. The objective of this research was to determine the quantity of water remaining in liquid phase, under different prefreezing conditions using pulsed nuclear magnetic resonance spectroscopy of dormant apple (Malus domestica Mill.) buds from three cultivars. During prefreezing, the quantity of water remaining in the liquid phase was less at -40 degrees C<-30 degrees C<-20 degrees C for all cultivars tested. The prefreezing temperature had a greater influence on reducing the quantity of liquid water than the duration of prefreezing. Prefreezing to -40 degrees C for 24 hours was optimal for ;Patterson' and ;McIntosh,' the hardiest cultivars, compared to -30 degrees C for 24 hours with ;Red Delicious.' Cryopreservation of dormant apple buds depends upon the quantity of liquid water during prefreezing, prior to immersion in liquid nitrogen, and upon the cultivar.


Simultaneous determination of zinc, cadmium and lead in environmental water samples by potentiometric stripping analysis (PSA) using multiwalled carbon nanotube electrode.
The present paper has focused on the potential application of multiwalled carbon nanotube for the development of a new, simple and highly selective electrochemical method for simultaneous Zn (II), Cd (II) and Pb (II) monitoring in water samples (lake and effluent waters), by using potentiometric stripping analysis (PSA). The electrochemical method is based on simultaneous preconcentration/reduction of metal ions onto a multiwall carbon nanotube electrode at -1.3V (versus Ag/AgCl(sat)) in 0.3 mol L(-1) acetate solution containing 15 mg L(-1) Hg (II) ions during 180s, followed by subsequent chemical stripping. The analytical curve for all analytes covered the linear range varying from 58.4 up to 646.2 microg L(-1) with correlation coefficients higher than 0.981. The limits of detection for Zn (II), Cd (II) and Pb (II) were found to be 28.0, 8.4 and 6.6 microg L(-1), while the relative standard deviation (RSD) at 352 microg L(-1) was 5.6, 7.1 and 5.6% (n=5), respectively. The behavior of the simultaneous determination in the presence of following ions Co (II), Cr (III) and Cu (II) was affected by using the analyte:interferent ratio 1:10. Therefore, by using standard addition method, Zn (II), Cd (II) and Pb (II) ions in lake and effluent water samples were determined after the spiking procedure and the results were successfully compared with those obtained by atomic absorption spectrometry (AAS). The obtained results suggest that the proposed method can be applied as a simple and efficient alternative for the simultaneous monitoring of heavy metals in water samples, according to those established requirements from environmental organizations. In addition, this method demonstrates the powerful application of carbon nanotubes in the field of potentiometric stripping analysis.


Renal malakoplakia mimicking a malignant renal carcinoma: a patient case with literature review.
Malakoplakia, a medical, surgical, pathological and radiological enigma, is an infrequent chronic inflammatory condition that can affect many organ systems, including the gastrointestinal tract, integument, skeletal system and genitourinary tract. Review of the literature has shown that malakoplakia presents in paediatric as well as adult populations, and that it is associated with impaired immune function. Variable clinical manifestations as well as the sometimes non-specific radiological findings of malakoplakia can be misleading, making diagnosis quite difficult. We present a clinical case of renal malakoplakia mimicking a malignant renal carcinoma in a 62-year-old woman. This report highlights the importance of awareness of malakoplakia in the differential diagnosis for renal masses and renomegaly. This case can serve as a reminder that things are not always what they seem, and it reinforces the idea that unusual disease entities should be explored to aid in achieving a correct diagnosis and, thus, potentially avoid unnecessary treatment.


[Evaluation of morbidity on the basis of mortality].
Prevalence and incidence rates of leading diseases are estimated by sex and age groups for the population of France aged 15 and over. "These estimations have been made on the basis of the regional statistics of causes of death in France, during the 1968-1970 period. A simple regression model has been used. The number of patients suffering from a given disease is defined as being the part of the population statistically linked to mortality by this disease. The results obtained can generally be compared to those available from other sources. As for cancers, it appears that the estimated annual number of new cases is four times higher than the number of registered new cases." (summary in ENG, GER)


Age-dependent hyperresponsiveness of spontaneously hypertensive rats to the pressor effects of intravenous neuropeptide Y (NPY): role of mode of peptide administration and plasma NPY-like immunoreactivity.
The effects of various doses of intravenously (i.v.) infused (5-min duration, 0.1-3.2 nmol/kg/min) or bolus-injected (0.1-3.2 nmol/kg) porcine and/or rat/human neuropeptide Y (NPY) on mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of porcine NPY-like immunoreactivity (pNPYir) were examined in conscious, unrestrained spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats of various ages. When administered as an infusion to 12- to 17-week-old SHR, WKY, and SD rats, porcine NPY (pNPY) was more potent in increasing MAP in SHR than in either WKY or SD rats. Infusions of rat/human NPY instead of pNPY resulted in similar increases in potency in 12- to 17-week-old SHR as compared with WKY. This potency-associated hyperresponsiveness to infused pNPY was also observed when 36- to 41-week-old and 6-week-old SHR and WKY were examined, but infused NPY induced similar HR reductions in age-matched rats regardless of rat strain. Furthermore, doses of infused pNPY that elicited significantly greater pressor responses in SHR and WKY (0.32 nmol/kg/min in 12- to 17-week-old rats and 1.0 nmol/kg/min in 6-week-old rats) resulted in essentially identical plasma pNPYir concentrations in the two rat strains. In contrast, hyperresponsiveness to the MAP effects of bolus injections of pNPY in 12- to 17-week-old SHR was manifested as an increase in efficacy rather than potency, was associated with significantly smaller reductions in HR in SHR than in WKY and occurred at plasma pNPYir concentrations that were significantly larger than those required for infusion-associated hyperresponsiveness. These results are consistent with the hypothesis that NPY is an important contributor to the development and maintenance of essential hypertension.


Effects of 47C allele (rs4880) of the SOD2 gene in the production of intracellular reactive species in peripheral blood mononuclear cells with and without lipopolysaccharides induction.
Challenging of peripheral blood mononuclear cells (PBMCs) with lipopolysaccharides (LPS) has been shown to activate monocytes and macrophages, leading to the production of pro-inflammatory cytokines and reactive oxygen species (ROS). Manganese superoxide dismutase (MnSOD) is an important enzyme that may play a central role in the response to oxidative stress. 47C> T SNP of the SOD2 gene, the -9Val MnSOD is less efficient than the -9Ala version. We have previously characterized the cellular redox status of human PBMCs expressing either -9Ala (CC) or -9Val (TT) SOD2 and analyzed the responses of these cells to oxidative stress induced by LPS. Due to the observed alterations in the activities of these antioxidant enzymes, we decided to investigate their immunocontent and analyze the production of intracellular oxidants, as well as any resulting DNA damage. PBMCs were isolated from the blood of 30 healthy human volunteers (15 volunteers per allele). We then analyzed levels of nitrite, DNA damage by comet assay, TNF-α, carboxymethyl lysine and nitrotyrosine and assessed production of intracellular reactive species by the DCFH-DA-based assay and western blots were used to analyze protein levels. Our results show that there occurs an increase in nitric oxide production in both allele groups after challenge with LPS. A significant increase in DNA damage was observed in PBMCs after an 8-h LPS challenge. Cells expressing the SOD2 47C allele quickly adapt to a more intense metabolism by upregulating cellular detoxification mechanisms. However, when these cells are stressed over a long period, they accumulate a large quantity of toxic metabolic byproducts.


Advanced nasopharyngeal carcinoma: pre-treatment prediction of progression based on multi-parametric MRI radiomics.
We aimed to investigate the potential of radiomic features of magnetic resonance imaging (MRI) to predict progression in patients with advanced nasopharyngeal carcinoma (NPC). One hundred and thirteen consecutive patients (01/2007-07/2013) (training cohort: n = 80; validation cohort: n = 33) with advanced NPC were enrolled. A total of 970 initial features were extracted from T2-weighted (T2-w) (n = 485) and contrast-enhanced T1-weighted (CET1-w) MRI (n = 485) for each patient. We used least absolute shrinkage and selection operator (Lasso) method to select features that were most significantly associated with the progression. The selected features were used to construct radiomics-based models and the predictive performance of which were assessed with respect to the area under the curve (AUC). As a result, eight features significantly associated with the progression of advanced NPC were identified. In the training cohort, a radiomic model based on combined CET1-w and T2-w images (AUC: 0.886, 95%CI: 0.815-0.956) demonstrated better prognostic performance than models based on CET1-w (AUC: 0.793, 95%CI: 0.698-0.889) or T2-w images alone (AUC: 0.813, 95%CI: 0.721-0.904). These results were confirmed in the validation cohort. Accordingly, MRI-based radiomic biomarkers present high accuracy in the pre-treatment prediction of progression in advanced NPC.


A physiologically-based pharmacokinetic model of methotrexate incorporating hepatic excretion via multidrug-resistance-associated protein 2 (Mrp2) in mice, rats, dogs, and humans.
An updated physiologically-based pharmacokinetic (PBPK) model of methotrexate (MTX) was built based on an earlier model developed by Bischoff et al. (1971). MTX has been known to be a substrate of multidrug-resistance-associated protein 2 (Mrp2). A three-dimensional quantitative structure-activity relationship model (3D-QSAR) of Mrp2 was developed by Hirono et al. (2005). In our updated PBPK model of MTX, using the computational chemistry-derived binding affinity (Km), a Mrp2-mediated biliary excretion process was incorporated as the MTX excretory pathway. Our model simulation results are consistent with numerous datasets obtained from mice, rats, dogs, and humans, at a variety of dose levels. Comparisons were made between our updated PBPK model and the earlier one from Bischoff et al. using a PBPK Index approach. Our new PBPK model was further verified against additional pharmacokinetic datasets from rats under special experimental conditions (cannulated bile duct) and Eisai hyperbirilubinemic rats.


Comparison of the loads and antibiotic-resistance profiles of Enterococcus species from conventional and organic chicken carcasses in South Korea.
Antibiotic-resistant bacteria in poultry meat are a threat to public health. In this study, we compared the Enterococcus spp. loads and antibiotic-resistance profiles between carcasses of conventionally and organically raised chickens. A total of 144 chicken carcasses (72 conventional and 72 organic) was collected from local retail markets in Seoul, South Korea. Overall, 77.7% (112 of 144; 75% conventional and 80% organic) of chicken carcasses were positive for Enterococcus. The mean loads of Enterococcus spp. were greater in conventional chicken carcasses, at 2.9 ± 0.4 log CFU/mL, than those in organic chicken carcasses, at 1.78 ± 0.3 log CFU/mL (p < 0.05). A total of 104 isolates (52 from conventional and 52 from organic chicken carcasses) was randomly selected for further analysis. The predominant species was Enterococcus faecalis in both conventional and organic chicken carcasses (57.7 and 76.9%, respectively; P > 0.05). Rates of resistance to ciprofloxacin and erythromycin, which are used in veterinary medicine in South Korea, were significantly higher in conventional chicken carcasses than in organic chicken carcasses. However, we found no difference between the rates of resistance to antibiotics such as vancomycin and tigecycline, which were not registered for use in veterinary medicine in South Korea, of Enterococcus isolates from conventional and organic chicken carcasses. In addition, although multidrug resistant isolates were obtained from both types of chicken samples, the prevalence of samples positive for Enterococcus was significantly higher in conventional chicken carcasses than in organic chicken carcasses (P < 0.05). The most common multidrug resistance pattern was erythromycin-tetracycline-rifampicin in conventional chicken carcasses and quinupristin-dalfopristin-tetracycline-rifampicin in organic chicken carcasses. A high level of gentamicin resistance was observed in isolates from not only conventional (5.8%) but also organic chicken (1.9%) carcasses, with no significant difference in rates between them (P > 0.05). Despite this, our results suggest that organic food certification is effective in reducing fecal contamination and the burden of antibiotic-resistant Enterococcus spp. in chicken carcasses.


Recent developments in cold plasma-based enzyme activity (browning, cell wall degradation, and antioxidant) in fruits and vegetables.
According to the Food and Agriculture Organization of United Nations reports, approximately half of the total harvested fruits and vegetables vanish before they reach the end consumer due to their perishable nature. Enzymatic browning is one of the most common problems faced by fruit and vegetable processing. The perishability of fruits and vegetables is contributed by the various browning enzymes (polyphenol oxidase, peroxidase, and phenylalanine ammonia-lyase) and ripening or cell wall degrading enzyme (pectin methyl-esterase). In contrast, antioxidant enzymes (superoxide dismutase and catalase) assist in reversing the damage caused by reactive oxygen species or free radicals. The cold plasma technique has emerged as a novel, economic, and environmentally friendly approach that reduces the expression of ripening and browning enzymes while increasing the activity of antioxidant enzymes; microorganisms are significantly inhibited, therefore improving the shelf life of fruits and vegetables. This review narrates the mechanism and principle involved in the use of cold plasma technique as a nonthermal agent and its application in impeding the activity of browning and ripening enzymes and increasing the expression of antioxidant enzymes for improving the shelf life and quality of fresh fruits and vegetables and preventing spoilage and pathogenic germs from growing. An overview of hurdles and sustainability advantages of cold plasma technology is presented.


Similarity and difference in the processing of same- and other-race faces as revealed by eye tracking in 4- to 9-month-olds.
Fixation duration for same-race (i.e., Asian) and other-race (i.e., Caucasian) female faces by Asian infant participants between 4 and 9 months of age was investigated with an eye-tracking procedure. The age range tested corresponded with prior reports of processing differences between same- and other-race faces observed in behavioral looking time studies, with preference for same-race faces apparent at 3 months of age and recognition memory differences in favor of same-race faces emerging between 3 and 9 months of age. The eye-tracking results revealed both similarity and difference in infants' processing of own- and other-race faces. There was no overall fixation time difference between same race and other race for the whole face stimuli. In addition, although fixation time was greater for the upper half of the face than for the lower half of the face and trended higher on the right side of the face than on the left side of the face, face race did not impact these effects. However, over the age range tested, there was a gradual decrement in fixation time on the internal features of other-race faces and a maintenance of fixation time on the internal features of same-race faces. Moreover, the decrement in fixation time for the internal features of other-race faces was most prominent on the nose. The findings suggest that (a) same-race preferences may be more readily evidenced in paired comparison testing formats, (b) the behavioral decline in recognition memory for other-race faces corresponds in timing with a decline in fixation on the internal features of other-race faces, and (c) the center of the face (i.e., the nose) is a differential region for processing same- versus other-race faces by Asian infants.


Stress-sensing in the human greying hair follicle: Ataxia Telangiectasia Mutated (ATM) depletion in hair bulb melanocytes in canities-prone scalp.
Canities (or hair greying) is an age-linked loss of the natural pigment called melanin from hair. While the specific cause(s) underlying the loss of melanogenically-active melanocytes from the anagen hair bulbs of affected human scalp remains unclear, oxidative stress sensing appears to be a key factor involved. In this study, we examined the follicular melanin unit in variably pigmented follicles from the aging human scalp of healthy individuals (22-70 years). Over 20 markers were selected within the following categories: melanocyte-specific, apoptosis, cell cycle, DNA repair/damage, senescence and oxidative stress. As expected, a reduction in melanocyte-specific markers in proportion to the extent of canities was observed. A major finding of our study was the intense and highly specific nuclear expression of Ataxia Telangiectasia Mutated (ATM) protein within melanocytes in anagen hair follicle bulbs. ATM is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks and functions as an important sensor of reactive oxygen species (ROS) in human cells. The incidence and expression level of ATM correlated with pigmentary status in canities-affected hair follicles. Moreover, increased staining of the redox-associated markers 8-OHdG, GADD45 and GP-1 were also detected within isolated bulbar melanocytes, although this change was not clearly associated with donor age or canities extent. Surprisingly, we were unable to detect any specific change in the expression of other markers of oxidative stress, senescence or DNA damage/repair in the canities-affected melanocytes compared to surrounding bulbar keratinocytes. By contrast, several markers showed distinct expression of markers for oxidative stress and apoptosis/differentiation in the inner root sheath (IRS) as well as other parts of the hair follicle. Using our in vitro model of primary human scalp hair follicle melanocytes, we showed that ATM expression increased after incubation with the pro-oxidant hydrogen peroxide (H2O2). In addition, this ATM increase was prevented by pre-incubation of cells with antioxidants. The relationship between ATM and redox stress sensing was further evidenced as we observed that the inhibition of ATM expression by chemical inhibition promoted the loss of melanocyte viability induced by oxidative stress. Taken together these new findings illustrate the key role of ATM in the protection of human hair follicle melanocytes from oxidative stress/damage within the human scalp hair bulb. In conclusion, these results highlight the remarkable complexity and role of redox sensing in the status of human hair follicle growth, differentiation and pigmentation.


Trends of ear syringing at Ibadan, Nigeria.
Ear syringing is a procedure by which the external auditory canal is irrigated with a normal saline at body temperature. It is a procedure which every doctor or nurse should be able to perform proficiently. A study of 622 patients that needed ear syringing was done between December 1999 and June 2001 to determine its trend. There were 341(55%) males and 281(45%) females with age ranged from 3.5months to 89 years: 44.4% were in the first decade of life. Cerumen auris 99% remained the commonest indication for syringing in this study with bilateral cerumen auris constituting 53.1% while right and left cerumen auris constituted 24.4% and 21.5% respectively. Cerumen auris constituted 66% of total 933 Otologic cases seen during the study period. Other indications were otitis externa 0.7% (otomycosis 0.5%; bacterial 0.2%) and foreign body 0.3%. The majority of patients (86%) required between 500mls and 1000mls of fluid for irrigation and 94.9% required not more than one attempt at syringing. The complications recorded were mainly vertigo 0.2% and tympanic membrane perforation 0.2% respectively. Thus ear syringing, though simple and sometimes taken for granted may be fraught with dangers; it is a very safe procedure in trained hands and that after at least three attempts of ear syringing for cerumen auris and if it persists despite effective applications of cerumenolytic agents prior to irrigation, the procedure should be discontinued and other methods of imparted cerumen auris removal should be employed.


Silver Nanoantibiotics Display Strong Antifungal Activity Against the Emergent Multidrug-Resistant Yeast Candida auris Under Both Planktonic and Biofilm Growing Conditions.
Candida auris is an emergent multidrug-resistant pathogenic yeast with an unprecedented ability for a fungal organism to easily spread between patients in clinical settings, leading to major outbreaks in healthcare facilities. The formation of biofilms by C. auris contributes to infection and its environmental persistence. Most antifungals and sanitizing procedures are not effective against C. auris, but antimicrobial nanomaterials could represent a viable alternative to combat the infections caused by this emerging pathogen. We have previously described an easy and inexpensive method to synthesize silver nanoparticles (AgNPs) in non-specialized laboratories. Here, we have assessed the antimicrobial activity of the resulting AgNPs on C. auris planktonic and biofilm growth phases. AgNPs displayed a strong antimicrobial activity against all the stages of all C. auris strains tested, representative of four different clades. Under planktonic conditions, minimal inhibitory concentration (MIC) values of AgNPs against the different strains were <0.5 μg ml-1; whereas calculated IC50 values for inhibition of biofilms formation were <2 μg ml-1 for all, but one of the C. auris strains tested. AgNPs were also active against preformed biofilms formed by all different C. auris strains, with IC50 values ranging from 1.2 to 6.2 μg ml-1. Overall, our results indicate potent activity of AgNPs against strains of C. auris, both under planktonic and biofilm growing conditions, and indicate that AgNPs may contribute to the control of infections caused by this emerging nosocomial threat.


Investigation on chemical species of arsenic, selenium and antimony in fly ash from coal fuel thermal power stations.
Investigations of the existing chemical forms and the concentrations of arsenic (As), selenium (Se) and antimony (Sb) in samples of fly ash obtained from six coal-fired power stations in various countries were carried out. The concentration of As was found to vary from 5.4 to 22.3 mg kg(-1), and the most common mode of occurrence of As in the fly ashes is in association with carbonates or Fe-Mn oxides. The concentrations of Se and Sb ranged from 2.3-5.2 and 1.0-3.9 mg kg(-1), respectively. The dominant chemical forms of Se and Sb in the fly ashes were as extractable species. Also, water-soluble As, Se and Sb in the fly ashes were extracted, and the chemical species of As, Se and Sb in the extract determined using HPLC-ICP-MS. This was done as the potential release of soluble As, Se and Sb through leaching of fly ash is of environmental concern. The most abundant form of As in the extract was the low toxicity As(V). The main species of Se was Se(IV), although it was found that the ratio of Se(VI) to Se(IV) in acidic fly ashes is higher than in alkaline fly ash samples. Antimony was mostly present as Sb(III).


The bHLH gene Hes1 is essential for expansion of early T cell precursors.
Mice mutant for the bHLH gene Hes1, which is known to keep cells in a proliferative state, mostly lack thymus. Transfer of Hes1-null fetal liver cells into RAG2-null host mice normally reconstitutes B cells but fails to generate mature T cells in the thymus. In the reconstituted thymus, T cell differentiation is arrested at the CD4(-)CD8(-) double negative (DN) stage. Both the initial T cell receptor (TCR)-independent and the subsequent TCR-dependent selective expansion during the DN stage are severely affected. Thus, Hes1 is essential for the earliest thymocyte expansion in a cell-autonomous manner.


High methanol-to-formate ratios induce butanol production in Eubacterium limosum.
Unlike gaseous C1 feedstocks for acetogenic bacteria, there has been less attention on liquid C1 feedstocks, despite benefits in terms of energy efficiency, mass transfer and integration within existing fermentation infrastructure. Here, we present growth of Eubacterium limosum ATCC8486 using methanol and formate as substrates, finding evidence for the first time of native butanol production. We varied ratios of methanol-to-formate in batch serum bottle fermentations, showing butyrate is the major product (maximum specific rate 220 ± 23 mmol-C gDCW-1 day-1 ). Increasing this ratio showed methanol is the key feedstock driving the product spectrum towards more reduced products, such as butanol (maximum titre 2.0 ± 1.1 mM-C). However, both substrates are required for a high growth rate (maximum 0.19 ± 0.011 h-1 ) and cell density (maximum 1.2 ± 0.043 gDCW l-1 ), with formate being the preferred substrate. In fact, formate and methanol are consumed in two distinct growth phases - growth phase 1, on predominately formate and growth phase 2 on methanol, which must balance. Because the second growth varied according to the first growth on formate, this suggests butanol production is due to overflow metabolism, similar to 2,3-butanediol production in other acetogens. However, further research is required to confirm the butanol production pathway in E. limosum, particularly given, unlike other substrates, methanol likely results in mostly NADH generation, not reduced ferredoxin.


[Persistent pulmonary hypertension in a neonate].
The author gives an account of recent findings on the pathophysiology and treatment of persisting pulmonary hypertension in a neonate. His own experience with treatment is documented in case-histories. He emphasizes the marked therapeutic effect of hyperoxic hyperventilation.


The impact of COVID-19-related smell and taste disorders on a patient with bulimia nervosa: a case report.
A large number of patients with COVID-19 will suffer from long-term smell and taste disorders (STD). These STD symptoms could have a significant impact on patients with an eating disorder (ED). To highlight this issue, a case is presented of a patient with bulimia nervosa who experienced COVID-19-relate STD symptoms. Clinicians should reassess patients with an ED who suffer from COVID-19 with STD symptomatology and potentially redirect treatment. More research is needed on STD symptoms in patients with an ED to improve our knowledge on the role of smell and taste in disordered eating behaviors and improve treatment guidelines.


Flow effects on the surface properties of surfactant foam films.
The surface electrostatic properties of liquid foam, involving the electrokinetic (EK) phenomena in the liquid-gas interface, have significant effects on the stability of the foam. Here, we established a theoretical model for ion transport in liquid films by combining the liquid flow and surface reaction. We found that the surface electrostatic properties of liquid foams were influenced unexpectedly by the pressure-induced flow. The liquid flow will induce the potential and concentration differences in the flow direction. When the pressure drop increases to a certain high value, the induced potential and salt concentration difference increases, leading to the change of the surface electrostatic properties such as zeta potential and the surface charge density. This change shows that the surface electrostatic properties of foam films depend on the coupling of various factors including ion distribution and pressure drop, which deepens our understanding of the electrostatic properties of the foam films.


The effectiveness of low-dosed outpatient biopsychosocial interventions compared to active physical interventions on pain and disability in adults with nonspecific chronic low back pain: A protocol for a systematic review with meta-analysis.
Best outpatient treatment of nonspecific chronic low back pain is high-dosed exercise that is maintained after therapy. Primary care biopsychosocial intervention (PCBI) is an outpatient multicomponent intervention that includes an active component (exercise, physical activity, or physiotherapy) and at least one psychological, social, or occupational component. Research has shown that PCBI can reduce pain intensity and disability. While scattered studies support low-dosed (<15 treatment hours) PCBI, there is no systematic review comparing the effectiveness of low-dosed PCBI treatment with traditional physical activity interventions in adults with nonspecific chronic low back pain (CLBP). Randomised controlled trials that evaluate low-dosed outpatient biopsychosocial interventions compared to physical treatment with an active component such as exercise, physical activity or usual physiotherapy treatment for adult participants (18 years or older) who suffer from nonspecific CLBP will be included. A comprehensive search of multiple databases will be used to find relevant studies. The databases will be searched from inception to December 2021, with English or German language restrictions imposed. Keywords and derivatives of "chronic back pain", "exercise intervention", "cognitive-behavioral therapy", "primary care" and "randomized controlled trials" will be used. Sources will include CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid Medline, Physiotherapy Evidence Database (PEDro), PubMed and Web of Science. To our knowledge, this will be the first systematic review and meta-analysis of narrowly defined low- dosed PCBI across populations with nonspecific chronic low back pain. The objective of this review is to evaluate the effectiveness of low-dosed outpatient biopsychosocial interventions versus physical active interventions on pain intensity and disability in adults with CLBP. This study will provide evidence that could improve treatment options for patients with nonspecific CLBP. Systematic review registration number: PROSPERO 2022 CRD42022302771. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022302771.


Genetical genomics in livestock: potentials and pitfalls.
Genetical genomics combines gene mapping and gene expression approaches to identify loci controlling gene expression (eQTLs) that may underlie functional trait variation. The combination of genomic tools has great potential to facilitate dissection of complex traits, but studies need careful design and interpretation. Here we explore both the potential and the pitfalls of this approach with illustrations from actual studies. There are now an appreciable number of studies in model species and even humans demonstrating the feasibility of genetical genomics. However, most studies are too limited in size and design to unlock the full potential of the approach. Limited statistical power of studies exacerbates the problem of detection of false-positive eQTL and some reported results should be interpreted with caution. As one approach to more successful implementation of genetical genomics, we propose to combine expression studies with fine mapping of functional trait loci. This synergistic approach facilitates the implementation of genetical genomics for species without inbred resources but is equally applicable to model species. These properties make it particularly suitable for livestock populations where many QTL are already in the public domain and potentially very large pedigreed populations can be accessed.


Generation of DOPA-producing astrocytes by retroviral transduction of the human tyrosine hydroxylase gene: in vitro characterization and in vivo effects in the rat Parkinson model.
Astrocytes secreting high levels of L-3,4-dihydroxyphenylalanine (DOPA) have been generated by retrovirus-mediated transfer of the human tyrosine hydroxylase (TH) gene. Immature astrocytes obtained from prenatal rat brain were cocultured with TH virus producing psi-2 cells that had been pretreated with the mitosis inhibitor mitomycin-C. During the first week of coculture DOPA production gradually increased to reach a plateau after 7-9 days. At this time point virtually all cells were GFAP positive and over 80% of them expressed TH. DOPA production in the transduced astrocytes was largely independent of exogenous cofactor, and DOPA release into the medium was not influenced by addition of either KCl or tetrodotoxin or by removal of Ca2+ from the culture medium, indicating that the newly synthesized DOPA was constitutively released from the cells. Transplantation of the TH-transduced astrocytes to the striatum in unilaterally 6-hydroxydopamine lesioned rats reduced apomorphine-induced turning by about 50% at 2 weeks postgrafting. Microscopic analysis revealed that the transduced astrocytes survived very well after transplantation and that some of the grafted cells had migrated out, partly along blood vessels, into the surrounding striatum. TH expression was observed in cells with both the appearance of mature GFAP-positive astrocytes, as well as in more immature-looking cells. However, only a few percent of all transplanted cells maintained significant expression of the transgene, as determined by TH immuno-histochemistry. The results show that primary astrocytes may be highly useful as gene carriers for ex vivo gene therapy in the CNS. With future improvement in the gene transduction procedure for more efficient, sustained expression of the TH transgene in vivo, genetically engineered DOPA-producing astrocytes hold great promise as a tool to explore the potential of ex vivo gene therapy in Parkinson's disease.


Progress on structural modification of Tetrandrine with wide range of pharmacological activities.
Tetrandrine (Tet), derived from the traditional Chinese herb Fangji, is a class of natural alkaloids with the structure of bisbenzylisoquinoline, which has a wide range of physiological activities and significant pharmacfological effects. However, studies and clinical applications have revealed a series of drawbacks such as its poor water solubility, low bioavailability, and the fact that it can be toxic to humans. The results of many researchers have confirmed that chemical structural modifications and nanocarrier delivery can address the limited application of Tet and improve its efficacy. In this paper, we summarize the anti-tumor efficacy and mechanism of action, anti-inflammatory efficacy and mechanism of action, and clinical applications of Tet, and describe the progress of Tet based on chemical structure modification and nanocarrier delivery, aiming to explore more diverse structures to improve the pharmacological activity of Tet and provide ideas to meet clinical needs.


The antibacterial activity of haemin compared with cobalt, zinc and magnesium protoporphyrin and its effect on potassium loss and ultrastructure of Staphylococcus aureus.
The unique antibacterial properties of Fe-protoporphyrin (haemin) on Staphylococcus aureus, compared to Co-protoporphyrin (Co-PP), Mg-protoporphyrin (Mg-PP) and Zn-protoporphyrin (Zn-PP) are described. Only haemin (20 microM) exhibits a strong light-independent antibacterial effect on S. aureus; the other metalloporphyrins, Co-PP, Mg-PP or Zn-PP, have no antibacterial effect in the dark. Only light photosensitization of Mg-PP-treated cells resulted in the inhibition of the bacterial growth, while Co-PP or Zn-PP were photodynamically inactive. A notable effect of haemin on inactivation of S. aureus was the induction of immediate ion fluxes as determined by X-ray microanalysis (XRMA) of fast-frozen cells. A marked efflux of K (96%) and Cl (94%) was expressed immediately as determined by X-ray microanalysis of S. aureus cells treated with haemin for 5 min. Only 48% loss of Na was detected in the cells under these treatment conditions, while P content was increased by 150%. Electron microscopy analysis revealed the appearance of a mesosome-like structure connected to the new septa, filamentous chromosome and arrays of aggregated ribosomes in the cytoplasm. We propose that haemin has multiple cellular targets for its oxidative effect in S. aureus.


p38 MAPK: a dual role in hepatocyte proliferation through reactive oxygen species.
p38 MAPKs are important mediators of signal transduction that respond to a wide range of extracellular stressors such as UV radiation, osmotic shock, hypoxia, pro-inflammatory cytokines, and oxidative stress. The most abundant family member is p38α, which helps to couple cell proliferation and growth in response to certain damaging stimuli. In fact, increased proliferation and impaired differentiation are hallmarks of p38α-deficient cells. It has been reported that reactive oxygen species (ROS) play a critical role in cytokine-induced p38α activation. Under physiological conditions, p38α can function as a mediator of ROS signaling and either activate or suppress cell cycle progression depending on the activation stimulus. The interplay between cell proliferation, p38 MAPK activation, and ROS production plays an important role in hepatocytes. In fact, low levels of ROS seem to be needed to activate several signaling pathways in response to hepatectomy and to orchestrate liver regeneration. p38 MAPK works as a sensor of oxidative stress and cells that have developed mechanisms to uncouple p38 MAPK activation from oxidative stress are more likely to become tumorigenic. So far, p38α influences the redox balance, determining cell survival, terminal differentiation, proliferation, and senescence. Further studies would be necessary in order to clarify the precise role of p38 MAPK signaling as a redox therapeutical target.


Subjective signs of efficacious inferior alveolar nerve block in children.
This study is designed to examine the clinical signs relating to profound anesthesia of the primary dentition using the inferior alveolar nerve block (IANB) injection. The IANB injection has been used for many years for both adults and children to anesthetize the mandibular teeth. Most dentists are quite familiar with the signs of profound intraoral anesthesia in the adult. Because of infrequent exposure, they might not be as aware of the signs of adequate anesthesia on the child patient. Additionally, the dentist may not be able to differentiate apprehensive behavior from behavior elicited with inadequate pulpal anesthesia. The study consisted of forty male and female children. The subjects who ranged in age from 3 years to 12 years, with a mean age of 7 years, were scheduled for routine restorative care of mandibular primary teeth. Each subject was injected with 1.8 ml of 2 percent xylocaine, 1:100,000 epinephrine using the mandibular-block technique. Anesthesia was evaluated using direct ice placement, lip reaction, tongue reaction and gingival reaction at intervals of 0, 1, 2, and 5 minutes. The results showed a correlation of lip and tongue anesthesia and pulpal anesthesia over time. A stronger correlation existed with gingival anesthesia and pulpal anesthesia over time. There was no statistical relationship between the subject response to ice and pulpal anesthesia.


Relation between risk of falls, sarcopenia and parameters assessing quality of skeletal muscles in a group of postmenopausal women.
Involutional changes that occur in skeletal muscle are a feature that characterizes the aging process. In women, age-related decreases in muscle mass and function of skeletal muscles occur more rapidly with the onset of menopause. Progressive muscle dysfunction has been directly linked with an increased probability of falls, fractures, disability and mortality. To assess the relationship between the risk of falls and parameters of skeletal muscle assessment in a group of postmenopausal women together with the identification of patients with sarcopenia. This study was carried among 122 women over 60 years of age. Patients had their muscular system tested with the emphasis on the sarcopenia diagnosis using: Total Body Composition, handgrip and physical performance tests. Patients also underwent a questionnaire survey assessing occurrence of falls. The analysis showed an over 2-fold increase (OR 2.4; 95% CI, 1.02-5.56) in risk of falls in a year among subjects with decreased muscle mass. No such correlation was noted with parameters such as falls in the last 12 months and decrease of muscle strength as well as physical performance. Sarcopenia is more likely to be diagnosed with European Working Group on Sarcopenia in Older People (EWGSOP1) criteria than EWGSOP2 (updated in 2018) (18% vs. 4.1% respectively). The increased risk of falls has not been proven in women with sarcopenia. The decrease of muscle mass is significantly correlated with the risk of falls in the last year in postmenopausal women. Impact of sarcopenia on the risk of falls depends on diagnostic criteria.


Instant Stress: Detection of Perceived Mental Stress Through Smartphone Photoplethysmography and Thermal Imaging.
A smartphone is a promising tool for daily cardiovascular measurement and mental stress monitoring. A smartphone camera-based photoplethysmography (PPG) and a low-cost thermal camera can be used to create cheap, convenient, and mobile monitoring systems. However, to ensure reliable monitoring results, a person must remain still for several minutes while a measurement is being taken. This is cumbersome and makes its use in real-life situations impractical. We proposed a system that combines PPG and thermography with the aim of improving cardiovascular signal quality and detecting stress responses quickly. Using a smartphone camera with a low-cost thermal camera added on, we built a novel system that continuously and reliably measures 2 different types of cardiovascular events: (1) blood volume pulse and (2) vasoconstriction/dilation-induced temperature changes of the nose tip. 17 participants, involved in stress-inducing mental workload tasks, measured their physiological responses to stressors over a short time period (20 seconds) immediately after each task. Participants reported their perceived stress levels on a 10-cm visual analog scale. For the instant stress inference task, we built novel low-level feature sets representing cardiovascular variability. We then used the automatic feature learning capability of artificial neural networks to improve the mapping between the extracted features and the self-reported ratings. We compared our proposed method with existing hand-engineered features-based machine learning methods. First, we found that the measured PPG signals presented high quality cardiac cyclic information (mean pSQI: 0.755; SD 0.068). We also found that the measured thermal changes of the nose tip presented high-quality breathing cyclic information and filtering helped extract vasoconstriction/dilation-induced patterns with fewer respiratory effects (mean pSQI: from 0.714 to 0.157). Second, we found low correlations between the self-reported stress scores and the existing metrics of the cardiovascular signals (ie, heart rate variability and thermal directionality) from short measurements, suggesting they were not very dependent upon one another. Third, we tested the performance of the instant perceived stress inference method. The proposed method achieved significantly higher accuracies than existing precrafted features-based methods. In addition, the 17-fold leave-one-subject-out cross-validation results showed that combining both modalities produced higher accuracy than using PPG or thermal imaging only (PPG+Thermal: 78.33%; PPG: 68.53%; Thermal: 58.82%). The multimodal results are comparable to the state-of-the-art stress recognition methods that require long-term measurements. Finally, we explored effects of different data labeling strategies on the sensitivity of our inference methods. Our results showed the need for separation of and normalization between individual data. The results demonstrate the feasibility of using smartphone-based imaging for instant stress detection. Given that this approach does not need long-term measurements requiring attention and reduced mobility, we believe it is more suitable for mobile mental health care solutions in the wild.


On the correlation of a naturally and an artificially dichotomized variable.
A method is suggested for estimating the correlation of a naturally (X) and an artificially (Y) dichotomized variable. It is assumed that a normal random variable (L) underlies the artificially dichotomized variable. The proposed correlation coefficient recovers the product moment correlation coefficient between X and L from a fourfold table of X and Y. The suggested correlation coefficient nu is contrasted with the phi correlation and the biserial eta. The biserial eta was proposed by Karl Pearson and is conceptually related to the new correlation coefficient. However, in addition, Pearson's biserial eta invokes the assumption that the marginal distribution of L is normal, which contradicts its basic assumptions and thus does not recover the true correlation of L and X. Finally, an approximation is provided to simplify the calculation of nu and its standard error.


Distinct networks of periaqueductal gray columns in pain and threat processing.
Noxious events that can cause physical damage to the body are perceived as threats. In the brainstem, the periaqueductal gray (PAG) ensures survival by generating an appropriate response to these threats. Hence, the experience of pain is coupled with threat signaling and interfaces in the dl/l and vlPAG columns. In this study, we triangulate the functional circuits of the dl/l and vlPAG by using static and time-varying functional connectivity (FC) in multiple fMRI scans in healthy participants (n = 37, 21 female). The dl/l and vlPAG were activated during cue, heat, and rating periods when the cue signaled a high threat of experiencing heat pain and when the incoming intensity of heat pain was unknown. Responses were significantly lower after low threat cues. The two regions responded similarly to the cued conditions but showed prominent distinctions in the extent of FC with other brain regions. Thus, both static and time-varying FC showed significant differences in the functional circuits of dl/l and vlPAG in rest and task scans. The dl/lPAG consistently synchronized with the salience network and the thalamus, suggesting a role in threat detection, while the vlPAG exhibited more widespread synchronization and frequently connected with memory/language and sensory regions. Hence, these two PAG regions process heat pain when stronger pain is expected or when it is uncertain, and preferentially synchronize with distinct brain circuits in a reproducible manner. The dl/lPAG seems more directly involved in salience detection, while the vlPAG seems engaged in contextualizing threats.


miR-375 mediated acquired chemo-resistance in cervical cancer by facilitating EMT.
Acquired chemo-resistance is one of the key causal factors in cancer death. Emerging evidences suggest that miRNA and epithelial-mesenchymal transition play critical roles in the chemo-resistance in cancers. Here, we showed the association of paclitaxel-resistance with miR-375 over-expression and epithelial-mesenchymal transition inducement in cervical cancer. Using different cervical cancer cell models, we found that paclitaxel transiently induced up-regulation of miR-375 expression, proliferation inhibition, transition from epithelial to mesenchymal phenotype, and consequently impaired paclitaxel sensitivity. Forced over-expression of miR-375 may suppress Ecadherin expression by a directly targeting pathway, which led to paclitaxel resistance. Contrarily, re-expression of Ecadherin partly reversed epithelial-mesenchymal transition phenotype and miR-375 induced paclitaxel-resistance. Our findings suggest that paclitaxel-induced miR-375 over-expression facilitates epithelial-mesenchymal transition process via directly targeting Ecadherin, proliferation inhibition, and consequently results in chemo-resistance in cervical cancer cells. A reversion of miR-375 or Ecadherin expression may be a novel therapeutic approach for overcoming chemo-resistance in cervical cancer.


Molecular evolution of Drosophila cuticular protein genes.
Several multigene families have been described that together encode scores of structural cuticular proteins in Drosophila, although the functional significance of this diversity remains to be explored. Here I investigate the evolutionary histories of several multigene families (CPR, Tweedle, CPLCG, and CPF/CPFL) that vary in age, size, and sequence complexity, using sequenced Drosophila genomes and mosquito outgroups. My objective is to describe the rates and mechanisms of 'cuticle-ome' divergence, in order to identify conserved and rapidly evolving elements. I also investigate potential examples of interlocus gene conversion and concerted evolution within these families during Drosophila evolution. The absolute rate of change in gene number (per million years) is an order of magnitude lower for cuticular protein families within Drosophila than it is among Drosophila and the two mosquito taxa, implying that major transitions in the cuticle proteome have occurred at higher taxonomic levels. Several hotspots of intergenic conversion and/or gene turnover were identified, e.g. some gene pairs have independently undergone intergenic conversion within different lineages. Some gene conversion hotspots were characterized by conversion tracts initiating near nucleotide repeats within coding regions, and similar repeats were found within concertedly evolving cuticular protein genes in Anopheles gambiae. Rates of amino-acid substitution were generally severalfold higher along the branch connecting the Sophophora and Drosophila species groups, and 13 genes have Ka/Ks significantly greater than one along this branch, indicating adaptive divergence. Insect cuticular proteins appear to be a source of adaptive evolution within genera and, at higher taxonomic levels, subject to periods of gene-family expansion and contraction followed by quiescence. However, this relative stasis is belied by hotspots of molecular evolution, particularly concerted evolution, during the diversification of Drosophila. The prominent association between interlocus gene conversion and repeats within the coding sequence of interacting genes suggests that the latter promote strand exchange.


Could kDNA-PCR in Peripheral Blood Replace the Examination of Bone Marrow for the Diagnosis of Visceral Leishmaniasis?
The aim of this study was to evaluate whether the molecular (kDNA-PCR) and parasitological diagnosis in peripheral blood (PB) could replace the invasive and painful bone marrow collection (BM) in the diagnosis of visceral leishmaniasis (VL). PB from suspected VL patients was evaluated by parasitological and molecular techniques using as the gold standard (GS) a combination of clinical, epidemiological, and immunochromatographic test (PB-rK39) results and parasitological examination of BM. Based on the GS, 38 samples from 32 patients were grouped: Group 1, 20 samples of VL cases, and Group 2, 18 samples of non-VL cases. In order to evaluate the parasitological and molecular techniques in PB, the samples were examined. From Group 1, PB kDNA-PCR was positive in 20 samples and in 19 of 20 in BM kDNA-PCR examination. However, the parasitological examination of buffy coat was insensitive, being able to detect only 4 cases from Group 1. All samples from Group 2 were negative. We concluded that, for the diagnosis of visceral leishmaniasis, the parasitological examination of peripheral blood was not useful; however, molecular diagnosis by kDNA-PCR, performed in peripheral blood, could be useful to replace the parasitological examination of bone marrow.


Breast cancer survivors' beliefs and preferences regarding technology-supported sedentary behavior reduction interventions.
Less time spent in sedentary behaviors is associated with improved health and disease outcomes in breast cancer survivors. However, little is known about survivors' interest in sedentary behavior reduction interventions and how to effectively reduce this risk behavior. The purpose of this study was to explore breast cancer survivors' interest in and preferences for technology-supported sedentary behavior reduction interventions. Breast cancer survivors [n=279; Mage =60.7 (SD=9.7)] completed a battery of online questionnaires. Descriptive statistics were calculated for all data. To examine potential relationships between demographic, disease and behavioral factors, and survivors' interest in a technology-supported sedentary behavior reduction intervention, we conducted logistic regression analyses. These same factors were examined in relation to the perceptions of the effectiveness of such intervention using multiple regression analyses. On average, survivors spent 10.1 (SD=4.3) hours/day in sedentary activity. They believed prolonged periods of sedentary behavior were harmful to their health (87.0%) and that reducing sedentary behavior could improve their health (88.4%). Survivors believed they should move around after 30-60 (56.7%) or ≥60 (29.9%) minutes of sedentary behavior and indicated they were most likely to replace sedentary behaviors with walking around (97.1%) or walking in place (73.4%). The majority of survivors (79.9%) was interested in participating in a technology-supported sedentary behavior reduction intervention and indicated they would use a smartphone application (61.3%) 2-3 times/day (48.0%), 6 to 7 days/week (52.0%). Most survivors (73.5%) believed reminders would help them decrease sedentary behavior and preferred they be delivered after sitting for 60 minutes (60.5%) via vibrations on a wrist worn activity tracker (77.3%) or text messages (54.4%). Technology-supported sedentary behavior reduction interventions may be feasible and acceptable to breast cancer survivors. Data regarding user preferences for content, features, delivery mode and design will aid researchers in developing sedentary interventions that are potentially more relevant and effective from the outset.


Clinical characteristics of hospitalized psychotic patients who refuse antipsychotic drug therapy.
Thirty psychotic patients who refused antipsychotic medication were compared with 30 patients matched for age, sex, treatment ward, commitment status, and diagnosis who consented to drug treatment. Refusers were no more assaultive or combative than consenters; they were less often diagnosed as having schizophrenia and more often diagnosed as having bipolar or schizoaffective illness. A comparison between 17 of the least symptomatic refusers and 17 of the most persistent refusers showed that persistent refusers were more likely to have a diagnosis of schizophrenia; least symptomatic refusers were more often diagnosed as having affective disorders or schizoaffective disorders.


On the mechanism of actomyosin ATPase from fast muscle.
The labeled inorganic phosphate formed by enzymatic hydrolysis of [gamma-18O]ATP in normal water was derivatized to trimethyl phosphate and analyzed for the proportions of [18O3]Pi, [18O2]Pi, [18O1]Pi, and [18O0]Pi. The proportions observed were correlated with the kinetics of intermediate exchange by using a kinetic relationship in which it is assumed that binding of ATP and subsequent release of products are irreversible. Actomyosin and acto-heavy meromyosin catalyze intermediate exchange at a mean rate that is more than 1 order of magnitude slower than that predicted by rapid kinetic studies or implied by the essentially complete intermediate exchange observed with myosin alone. The reason for the slow apparent exchange is that there are two ATPase activities with different exchange properties. The effect of varying heavy meromyosin concentrations at a constant actin concentration shows that the two activities are interrelated and suggests further that one is due to ATP hydrolysis by the undissociated actomyosin crossbridge.