Quick identification and epidemiological characterization of Francisella tularensis by MALDI-TOF mass spectrometry.
Currently, Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) is being evaluated for its efficacy as a fast bacterial typing tool due to its great speed compared to other molecular methods. In this study, we evaluated MALDI-TOF as a tool for quick identification and typing of Francisella tularensis. This study encompassed 86 strains from two different geographical origins (Spain and the Czech Republic), which were previously characterised by Pulsed-Field Gel Electrophoresis (PFGE) and Multiple-Locus Variable Number Tandem Repeat Analysis (MLVA). The direct colony method was used for microbial identification. High-quality spectra of the 86 strains were obtained and their main spectra profiles (MSPs) were created for epidemiological typing using MALDI-TOF. Based on the MSPs, principal components were generated and a dendrogram was constructed. An in-house MALDI-TOF library entry was created for each group of PFGE and MLVA strains based on their high-quality spectra. Two dendrograms were obtained using these entries and the unique peaks in each entry were searched. All strains were correctly identified to the species level. No clear divisions were found in the 86-strain dendrogram; however, Spanish and Czech strains appeared separately in dendrograms created using MLVA and PFGE entries. Entries from our in-house MALDI-TOF library revealed 2-4 biomarker peaks for the detection of the five PFGE groups and 1-12 biomarker peaks for the detection of the seven MLVA groups. Finally, two and one specific biomarkers were found in the Czech and Spanish strains, respectively. MALDI-TOF can be used to accurately identify F. tularensis strains in less than 15 min. Moreover, data on geographical origin and PFGE and MLVA groups could be obtained in less than one hour after colony growing.


Results from Viet Nam's 2022 report card on physical activity for children and youth.
The Active Healthy Kids 2022 Viet Nam Report Card provides an evidence-based assessment of 10 indicators of community and government-led initiatives that impact the physical activity levels of children and youth in Vietnam. A systematic framework developed by the Active Healthy Kids Global Alliance was used. Each indicator: Overall Physical Activity, Organized Sport Participation, Active Play, Active Transportation, Sedentary Behaviors, Physical Fitness, Family and Peers, School, Community and Environment, and Government, and a new indicator: Obesity was assessed against predefined benchmarks. EBSCOhost databases and Google Scholar were searched for relevant academic and grey literature (e.g., government reports) respectively to inform indicator grading. The School indicator received the highest grade 'A', followed by the Government indicator which was graded as 'B-'. Three indicators (Sedentary Behaviors, Family and Peers, Community and Environment) received 'C' grades. Active Transportation was graded 'D+'. Overall Physical Activity received the lowest grade of 'F'. Organized Sport and Physical Activity, Active Play, and Physical Fitness were not graded due to lack of data. Obesity was graded B-. This is the first physical activity report card for children and adolescents in Viet Nam. Evidence suggests that Vietnamese children and adolescents have low physical activity levels and high levels of sedentary behaviors. Initiatives to promote physical activity in children predominantly focus on promoting physical education in schools. Increased community-based programs promoting physical activity outside of school settings are required. Future research should address the surveillance gap in Organized Sport and Physical Activity, Active Play, and Physical Fitness.


Thrombosis and inflammatory bowel disease.
Interaction between thrombosis and inflammation is increasingly recognized. With this, interest has arisen in the role of thrombosis in inflammatory conditions, including the inflammatory bowel diseases. Although the association between active inflammatory bowel disease and thromboembolic complications has long been known, there has been a resurgence in research into the role of thrombosis and the hemostatic system in the pathogenesis of both ulcerative colitis and Crohn's disease. Here we review the increased frequency of thromboembolic complications occurring in patients with inflammatory bowel disease; whether thrombosis might play a part in the initiation and maintenance of inflammation in inflammatory bowel disease; abnormalities of the coagulation system found in patients with inflammatory bowel disease; platelet dysfunction in inflammatory bowel disease; the mechanisms by which hemostatic processes might be proinflammatory in inflammatory bowel disease; and how these interactions might impact not only on the prevention of complications, but also on the treatment of the underlying inflammation in inflammatory bowel disease.


Comparison of efficacy and safety of different tourniquet applications in total knee arthroplasty: a network meta-analysis of randomized controlled trials.
Total knee replacement (TKA) is an effective way to treat teratogenic and disabling knee diseases such as advanced osteoarthritis. Tourniquets are often used in TKA to reduce bleeding and to get a better visualization of the surgical field, while it is related to safety concerns. We did this network meta-analysis to comprehensively compare the efficacy and safety of various tourniquet application strategies. PubMed, Embase, Cochrane Library, CNKI, and WanFang Database were systematically searched from January 1990 to May 2020. A network meta-analysis with a frequentist framework was done to assess the relative efficacy and safety by comparing seven clinical important endpoints. 38 eligible studies that assessed 3007 participants who underwent TKA were included in this network meta-analysis. Tourniquet inflation before osteotomy then deflation after wound closure effectively reduce perioperative bleeding (WMD compared with control group -234.66, 95% CI [-409.19 to -60.13]), while shortening the operation time (WMD -8.98, 95%CI [-14.07 to -3.88]) and reducing postoperative complications, including DVT (OR -0.58, 95%CI [-1.19 to 0.03]) and minor wound complications (OR -1.38, 95%CI [-3.00 to 0.25]). No difference was found in the late postoperative knee pain and function outcomes. Using tourniquets during the entire operation can effectively reduce blood loss, but it also can cause many safety problems, including DVTs, wound oozing, delayed healing, and serious wound complications. Tourniquet inflation before osteotomy then deflation after wound closure effectively can reduce perioperative bleeding while shortening the operation time and reducing postoperative complications, so it could be the ideal tourniquet application strategy in TKA.Key messagesThis is the first study that comprehensively compared different tourniquet application strategies to evaluate their impact on postoperative recovery following TKA, and five clinically important endpoints were assessed in this study: perioperative blood loss, operation time, postoperative pain and function, and complications.We conclude that tourniquet inflation before osteotomy then deflation after wound closure could be the ideal tourniquet application strategy in TKA.


Expression of interleukin-6 is downregulated by 17-(allylamino)-17-demethoxygeldanamycin in human prostatic carcinoma cells.
Interleukin-6 (IL-6) is a pleiotropic cytokine that is associated with tumor metastasis and prostate cancer. We evaluated the mechanism and effect of 17-(allylamino)-17-demethoxygeldanamycin (17AAG), a novel inhibitor of heat shock protein 90 (Hsp90), on the IL-6 gene expression in human prostatic carcinoma (PC-3) cells. Quantitative IL-6 and IL-6 receptor (IL-6R) expressions were assessed using RT-PCR. The deregulation of 17AAG and phorbol 12-myristate 13-acetate (PMA) on the IL-6 gene was determined by ELISA and transient gene expression assays using an IL-6 reporter vector. Although the IL-6R is ubiquitously expressed by prostatic epithelium cells, the IL-6 expression is only found in advanced prostatic carcinoma cells, such as PC-3 and DU145. Further studies using RT-PCR indicated that 17AAG downregulated the gene expression of IL-6. ELISA and the transient gene expression assay revealed that 17AAG blocked the stimulation of PMA of IL-6 gene expression in PC-3 cells. The PMA-induced IL-6 gene expression is dependent on the NF-kappaB response element. However, the effect of 17AAG appears to be mediated via a region located at -149 to +8 bp upstream of the transcriptional starting site of the IL-6 gene, and might not be through the NF-kappaB signaling pathway. The present study reveals that IL-6 is transcriptionally downregulated in human prostatic carcinoma cells in response to 17AAG. This result suggests the presence of a novel Hsp90 mediation pathway that is involved in the deregulation on the transcription of the human IL-6 gene in human prostate cancer.


An antigen to remember: regulation of B cell memory in health and disease.
Vaccine success relies on the formation of immunity. Humoral immunity is critical and is mediated by long-lived antibody-secreting cells and memory B cells (MBCs). Chronic infectious diseases cause a significant global burden of disease; pathogens that evade the immune system can cause phenotypical and functional changes to immune memory populations. Thus, recent studies have focused on MBC subset function. IgM+ MBCs have emerged as important early responders in malaria. Atypical MBCs have functional qualities associated with exhaustion in chronic infectious diseases, but the requirements for their formation and where they localize remains unknown. Similarly, the T-bet-driven transcriptional program drives formation of MBCs phenotypically similar to atypical MBCs. Identifying protective or detrimental roles of MBC subsets, and their regulators, will be important for clinical intervention.


Relationships Between Periventricular Epicardial Adipose Tissue Accumulation, Coronary Microcirculation, and Left Ventricular Diastolic Dysfunction.
Obesity is related to left ventricular (LV) diastolic dysfunction, although its pathophysiological mechanism remains unclear. Epicardial adipose tissue (EAT) is an ectopic fat with paracrine effects on coronary circulation and myocardium. We hypothesized that left ventricle-specific (periventricular) EAT may deteriorate diastolic function by impairing coronary microcirculation. In protocol 1, 74 patients without obstructive narrowing of the left anterior descending artery on multidetector computed tomography (MDCT) underwent coronary flow reserve (CFR) examination to evaluate the relationship between EAT and coronary microcirculation. In protocol 2, 372 patients who underwent both MDCT and serial transthoracic Doppler echocardiographic (TTDE) examinations were enrolled to investigate the impact of periventricular EAT on changes in diastolic function. EAT volume was measured by MDCT. CFR and diastolic function were assessed by TTDE. Deterioration of LV diastolic function was defined as a ≥ 20% decrease in early diastolic mitral annular velocity. CFR was significantly correlated with periventricular EAT volume (r = -0.37; P = 0.001), but not with total EAT volume (r = -0.21; P = 0.071). Periventricular EAT volume (P = 0.010) was significantly associated with CFR independent of cardiovascular risk factors. Among the 372 patients who had serial TTDE examinations, the frequency of deteriorated LV diastolic function was lowest in the lower tertile of periventricular EAT, intermediate in the middle tertile, and highest in the upper tertile (12.9%, 21.0%, and 25.8%, respectively; P = 0.037). Age, diabetes mellitus, and periventricular EAT volume were significantly associated with deterioration of LV diastolic function (all P < 0.05). This study demonstrated the close association of periventricular EAT with impaired CFR and deteriorated LV diastolic function.


The vascular-disrupting agent combretastatin impairs splitting and sprouting forms of physiological angiogenesis.
Vascular-disrupting agents like combretastatin (CA-4-P), used to attenuate tumor blood flow in vivo, exert anti-mitotic and anti-migratory effects on endothelial cells in vitro. We tested whether anti-vascular or anti-angiogenic effects of CA-4-P are evident with physiological angiogenesis in skeletal muscle (EDL) due to sustained hyperemia (intraluminal splitting) and chronic muscle overload (abluminal sprouting). CA-4-P was given i.v. (25 mg/kg on alternate days for 14 days) to mice subjected to angiogenic stimuli (prazosin or synergist extirpation). The responses of femoral artery blood flow as well as capillarity, capillary ultrastructure, and levels of Rho GTPase were measured. Blood flow was unaffected in the sprouting angiotype, but decreased in the splitting angiotype, by CA-4-P. In contrast, CA-4-P attenuated the capillarity increase in both models, associated with reduced lamellipodia and filopodia formation. Muscle overload, but not hyperemia, was accompanied by an increase in Rho GTPase with CA-4-P. CA-4-P impaired the angiogenic response in both experimental models. This inhibitory effect was associated with a lower increase in femoral blood flow in splitting, whereas sprouting angiogenesis was accompanied by higher Rho activity consistent with the interruption of actin polymerization. Thus, CA-4-P may exert context-dependent anti-vascular and anti-angiogenic effects in vivo under physiological conditions.


Genome Sequence of the Acidophilic Ferrous Iron-Oxidizing Isolate Acidithrix ferrooxidans Strain Py-F3, the Proposed Type Strain of the Novel Actinobacterial Genus Acidithrix.
Extremely acidophilic iron-oxidizing Gram-positive bacteria comprise species within the phyla Firmicutes and Actinobacteria. Here, we report the 4.02-Mb draft genome of Acidithrix ferrooxidans Py-F3, which was isolated from a stream draining an abandoned copper mine and proposed as the type species of a new genus of Actinobacteria.


Morphometric evaluation of the temporomandibular joint on cone-beam computed tomography.
Evaluation of the temporomandibular joint (TMJ) pathologies with cone-beam computed tomography (CBCT) provides essential information about the bone structures of the TMJ. It is important to know the normal reference range when defining these pathologies. The aim of this study is to examine the morphometric and morphologic analyses of the bone structures of TMJ on the CBCT images in detail according to age, gender, and joint side. A total of 35 parameters related to the condylar process, articular tubercle, mandibular fossa, ramus of mandible, and joint space were examined on the CBCT images. These parameters were compared with the joint sides and gender, and correlated with age. Thirty-five parameters were evaluated. A statistically significant difference was found between genders in 22 parameters and joint sides in 6 parameters. When the correlation of parameters with age was examined; it was found that there was a very weak positive relationship in nine parameters, a weak positive relationship in one parameter, and a very weak relationship in the negative direction in two parameters. In this study, the condylar process, articular tubercle, mandibular fossa, ramus of mandible, and joint spaces, which are usually examined separately in the literature, were examined, and the normal reference range was determined for all these parameters. We think that these normal reference ranges will be useful for researchers interested in TMJ pathologies.


Nonmalignant papillary lesions of the breast at US-guided directional vacuum-assisted removal: a preliminary report.
This study was conducted to assess the accuracy of US-guided directional vacuum-assisted removal (US-DVAR) in evaluating nonmalignant papillary breast lesions. This retrospective study was approved by the institutional review board at our institution; patient consent was not required. We reviewed the clinical and pathology findings from a total of 39 papillary lesions diagnosed at vacuum-assisted removal in 37 patients (age range, 26-60 years; mean age, 44.5 years). Over the follow-up period, we evaluated whether any histologic upgrade occurred and whether or not residual lesions were detected on follow-up imaging. US-DVAR of 39 lesions yielded tissue that was classified as benign in 35 and atypical in 4. Of the 35 lesions that were diagnosed as histologically benign at US-DVAR, 2 were surgically excised. Both of them yielded benign results. Of the 33 benign lesions that were not surgically excised, 28 (85%) were not seen at radiographic follow-up. Of the four lesions diagnosed as atypical at US-DVAR that were surgically excised, all the four were benign. None proved to be malignant. The upgrade rate was 0.0% (95% confidence interval, 0-9%). Among our patients, diagnosis by US-DVAR of benign papillary lesions proved to be accurate, and benign papillary lesions at US-DVAR did not need to be surgically excised for accurate diagnosis.


In vivo and in vitro intervention with L-carnitine prevents abnormal energy metabolism in isolated diabetic rat heart: chemical and phosphorus-31 NMR evidence.
The beneficial effects of in vivo injections (200 mg/kg, twice daily) or in vitro perfusion (5.0 mM) of L-carnitine on an intrinsic abnormality in energy metabolism was investigated in isolated, perfused diabetic rat heart. Hearts were aerobically perfused for 60 min with elevated fatty acid substrate to simulate diabetic conditions. Phosphorus-31 nuclear magnetic resonance spectroscopy revealed a temporal decline in myocardial ATP levels (to approx 82%) during perfusion of diabetic hearts, but not in control hearts. This reduction was prevented by prior treatment in vivo with L-carnitine or by providing L-carnitine acutely in the perfusion medium. Chemical analysis of tissue extracts indicated that L-carnitine injections were effective in replenishing the decrease in total myocardial carnitine content which was present in diabetic hearts and in preventing the accumulation of long chain fatty acyl CoA. Perfusion with L-carnitine also attenuated the elevation of long chain fatty acyl CoA in diabetic hearts. This study gives additional support to the hypothesis that decreases in ATP which occur in the isolated, perfused diabetic heart are correlated with a concomitant elevation in long chain fatty acyl CoA, a known inhibitor of adenine nucleotide translocase. In the presence of elevated exogenous fatty acids, a primary deficiency in the total myocardial carnitine pool would result in elevations in tissue concentrations of long chain fatty acyl CoA since carnitine is a required carrier for transport of fatty acids into mitochondria. Replenishment of the carnitine in vivo was shown to be sufficient to prevent subsequent alteration in long chain fatty acyl CoA and ATP in isolated perfused diabetic hearts despite the burden of elevated fatty acid substrates.


Progression in a chemically induced transplantable human pancreas carcinoma.
A methylnitrosourea (MNU)-induced transplantable human pancreas carcinoma was examined, at 3, 12, 18 and 36 months after its development, for growth and invasiveness in nude mice, karyotypic alteration and the evolution of marker chromosomes. Progression in tumorigenicity and invasiveness of cells were evident by a significant increase in tumor diameters produced within 8 weeks by the cells at 36 months as compared to those developed by cells from 3-month-old cell lines. Chromosome analysis at 3 months showed normal 46 XX karyotype in about 80% and minor anomalies in 20% of the cells. At 12, 18 and 36 months, all cells were hyperdiploid with 53-61 chromosomes and several abnormal marker chromosomes. Marker chromosomes showed non-reciprocal translocations, deletions, inversion and isochromosomes. The absence of chromosome 13 from the earlier stage onward may have resulted in the loss of genes which suppress tumorigenicity. The increase in homogeneously staining regions of marker chromosome 3 at later stages appears to parallel the augmentation in tumor growth and mitotic indices.


Current trends in the pretreatment of microalgal biomass for efficient and enhanced bioenergy production.
Biofuels from microalgal biomass is among some of the promising sustainable energy technologies that can significantly replace the dependence on fossil fuels worldwide due to potentiality to lower CO2 emissions. Nevertheless, the extraction of biomolecules for biofuel generation is inhibited by the rigidity of the cellular structure of microalgal biomass. Various pretreatment strategies have been evaluated for their efficacy in microalgal cell wall disruption to enhance microalgal bioenergy production. However, the efficiency of the pretreatment methods depend on the particular species being treated due to the inherent variability of the composition of the cell wall. This paper reviews pretreatment strategies (mainly novel physical, chemical and physicochemical) employed in bioenergy generation from microalgal biomass, address existing constraints and provides prospects for economic and industrial-scale production. The authors have also discussed the different pretreatment methods used for biodiesel, bioethanol, and biohydrogen production.


Prader-Willi syndrome in siblings, due to unbalanced translocation between chromosomes 15 and 22.
In a family in which the father carried a balanced translocation between chromosomes 15 and 22 two of his children had Prader-Willi syndrome and an unbalanced chromosome complement, having lost the proximal bands from the long arm of chromosome 15. His four other surviving children were normal but carried a balanced translocation.


CT and myelogram findings of os odontoideum.
We reviewed the findings of CT and myelogram of cases of os odontoideum. The diagnosis was confirmed by conventional tomogram in all these cases. Four cases were further confirmed by trans-oral decompression. Cartilage was found between the os odontoideum and the odontoid process during operation in these 4 cases. Four of them had no history of trauma and 2 of them had an associated anomaly; one was Down's syndrome, and the other was barrel chest and congenital dislocation of hips. CT findings of os odontoideum in these cases were a constriction and/or a gap of bony structure between the os odontoideum and the odontoid process. Myelograms showed spinal stenosis as a result of atlanto-axial dislocation, or anterior extradural compression from overgrown cartilage and posteriorly dislocated tip of shortened odontoid process.


Experience of patients and practitioners with a team and technology approach to chronic back disorder management.
Although rural and remote residents face general challenges accessing health care in comparison to urban dwellers, care for musculoskeletal conditions like chronic back disorders (CBD) is particularly challenging for rural and remote residents due to lack of access to physical yherapists. Telerehabilitation such as secure videoconferencing offers one solution to this disparity in rural care delivery, but incorporating the perspectives of health practitioners and patients is important when developing new sustainable care models. This study investigated the experiences of practitioners and patients during a novel interprofessional model of assessment where an urban-based physical therapist used videoconferencing to virtually join a rural nurse practitioner and a rural patient with CBD. Patient surveys and semi-structured interviews of practitioners and patients were analyzed quantitatively and qualitatively. Most patients were "very satisfied" (62.1%) or "satisfied" (31.6%) with the overall experience, and "very" (63.1%) or "somewhat (36.9%) confident" with the assessment. Thematic analysis of interviews revealed that this novel assessment method identified: access to care for CBD, effective interprofessional practice, enhanced clinical care for CBD, and technology considerations. Patient satisfaction with the telerehabilitation model of care was high. Patients and practitioners reported their experiences were impacted by access to care, interprofessional practice, enhanced care for CBD and technology. These findings will be useful in the development of patient-centered models of care utilizing telehealth strategies.


Sensory information processing in the frog olfactory pathways. Experimental basis for modeling studies.
In the frog, unitary electrophysiological recordings have been extensively used to investigate odor processing along the olfactory pathways. By comparing spontaneous and odor-evoked activities of neuroreceptor, mitral and cortical cells, we have collected fundamental data relating to coding abilities of the three olfactory levels, the olfactory mucosa, the bulb and the cortex. Based on a synthesis of our experimental data related to GABAergic and dopaminergic involvement in the olfactory bulb, this paper aims to match this information with computational data and to discuss some questions on bulbar processing. This paper is also devoted to further analyze original results on coding properties of two functionally evidenced neuron subpopulations in the olfactory cortex. Thus, the assumption according to which some cortical neurons may work as temporal integrators while others as coincidence detectors is presented. Moreover, the pertinence that the neural code may be carried by a single spike with varying latency was demonstrated.


Associations between living arrangement and sexual and gender minority stressors among university students since the start of the COVID-19 pandemic.
To examine the associations between COVID-19-related living arrangements and sexual and gender minority (SGM)-related stressors (ie, identity concealment and familial rejection). N = 478 SGM university students (Mage = 22 years, SD = 4.00). SGM university students were surveyed cross-sectionally between May and August 2020 regarding SGM-related stressors and living arrangements since the start of COVID-19. Approximately half (48.7%) of the sample reported a living rearrangement to their parents' home due to COVID-19. Living rearrangement to parents' homes was associated with an increased degree of identity concealment (β [95% C.I.] = 0.62 [0.10, 1.15]; p = .020) and familial rejection (β [95% C.I.] = 1.56 [0.72, 2.41]; p < .001) since the start of COVID-19 compared to stably living without parents (34.3%). Stably living with parents (17.0%) was not associated with increased degree of SGM-related stressors compared to experiencing a living rearrangement. Stakeholders must consider the unique identity-related vulnerabilities of SGM students living with parents and who experience living rearrangements due to COVID-19.


Descriptive Analysis of an Interdisciplinary Musculoskeletal Program.
Interdisciplinary musculoskeletal programs address comorbidities confounding musculoskeletal conditions and serve as an alternative to the single provider model. Descriptive analysis of an interdisciplinary musculoskeletal program. Retrospective descriptive analysis of patients enrolled in an interdisciplinary musculoskeletal program. Retrospective subanalysis: cohort of patients enrolled in interdisciplinary program with low back pain compared to historical cohort of patients in a single provider clinic. Academic interdisciplinary musculoskeletal health program. Patients referred to program with at least one follow-up visit over a 2-year period. Interdisciplinary musculoskeletal program involving physiatry, pain anesthesia, nutrition, psychology, rheumatology, sleep medicine, nursing, and physical therapy. Patient Specific Functional Scale (PSFS), Oswestry Low Back Disability Index (ODI), number of magnetic resonance imaging (MRI) scans, computed tomography (CT) scans, opioid prescriptions; Press Ganey scores. One hundred and seventy-three patients were enrolled and had at least one follow-up visit. Twenty-four percent of patients with any musculoskeletal complaint demonstrated clinically significant improvements in total PSFS. Mean improvement in PSFS was + 0.864 (SD 1.94), which was a statistically significant improvement (P = .0005), but not clinically significant. Magnetic resonance imaging was ordered for 5% of patients, and no computed tomography scans were ordered. Six percent of patients received opioid prescriptions. Press Ganey scores: 96% responded favorably in regard to physician communication quality, 86% of patients responded favorably for access to care, and 78% responded favorably for care coordination. 27.8% of patients with low back pain in the interdisciplinary program achieved a significant decrease in their ODI, compared to 26.6% in the single provider clinic (P = .87). Interdisciplinary musculoskeletal programs are a promising model to improve the functioning of patients with musculoskeletal pain and decrease downstream utilization. These programs may be more appropriate for patients at higher risk of developing chronic pain.


Tailoring hybrid carrageenans from Mastocarpus stellatus red seaweed using microwave hydrodiffusion and gravity.
This work deals with the use of microwave hydrodiffusion and gravity (MHG) for the recovery of hybrid carrageenans with specific mechanical features together with bioactive compounds. For this purpose, Mastocarpus stellatus red seaweed was used as raw material and the most adequate MHG processing conditions were studied. The physicochemical properties of the algae and the corresponding biopolymers, the fundamental characterisation of the bioactive compounds from the extracts (antioxidant capacity, sulfate content, protein content, among others) and the rheological features of the formulated gels were analysed. Results indicated that MHG is an adequate technique for obtaining functional extracts with potential applications in the food and non-food fields. Hybrid carrageenans with a wide range of viscoelastic features were recovered by MHG, saving time compared to conventional methods. The yields obtained for the recovered hybrid carrageenans and bioactive fractions were comparable to those obtained in red algae with conventional techniques.


The DC-ERG as a highly sensitive measure of effects of prostaglandins.
A few microliters of a prostaglandin preparation (PGE2 or PGF2 alpha) were injected via the ora serrata into the posterior vitreous of one of the eyes in albino rabbits. The fellow eye received an equal volume of saline intravitreally and served as control. The DC electroretinogram (ERG) and the standing potential of the eye (SP) were recorded directly with corneal contact lenses, very stable calomel electrodes, and under very constant anesthesia. The b- and c-wave amplitudes increased in response to 0.1 and 1.0 microgram of PGE2 and PGF2 alpha, respectively. At medium doses there was an increase in the b- and c-wave amplitudes followed by a long-lasting reduction. At very high, nonphysiological doses of PGE2, b- and c-wave amplitudes decreased as compared with the control eye. Prostaglandins modify inflammatory reactions, influence ion transport across membranes, modulate synaptic transmission, and regulate blood flow to various organs. Effects of extremely low doses on the retina and pigment epithelium might indicate a transmitter-like nature of prostaglandins. The present experimental model might be of use in studies of inflammatory eye disease, prostaglandin inhibitors, and characteristics of the pigment epithelial membranes.


Cultural adaptation of the savvy caregiver program for Korean Americans with limited English proficiency: a feasibility and acceptability study.
Limited English proficiency (LEP) of dementia caregivers poses a critical barrier to these caregivers' access to evidence-based interventions. In an effort to make such interventions available and accessible to dementia caregivers with LEP, in the present study we use Barrera and colleagues' (2011) three-step model of cultural adaptation: (1) information gathering, (2) preliminary adaptation, and (3) full adaptation. Selecting Korean Americans as a target group and the Savvy Caregiver Program (SCP) as a target intervention, we demonstrate the sequential process of cultural adaption and report the outcomes on feasibility and acceptability. Preliminary adaptation with linguistic attunement was conducted by translating the SCP manual into Korean and certifying two lay individuals who were bilingual in English and Korean as Savvy trainers. The 6-week online SCP program was delivered by the two trainers in Korean with six to seven caregiver participants per trainer (N = 13). Feasibility and acceptability of the SCP for both caregiver participants and trainers were assessed using mixed methods, and their data then informed full adaptation. Findings not only showed the initial efficacy of the linguistically attuned SCP but also suggested areas for further modification. Data-driven assessment yielded a list of recommended changes for full adaptation, which was reviewed by the SCP developer to ensure fidelity and by community and research partners to confirm contextual and cultural relevance. The adopted changes are broadly summarized as representing logistical, technical, and cultural issues. Given our refined set of educational materials and implementation guidelines, we discuss future directions for research and development.


Effectiveness of nonadjuvanted monovalent influenza A(H1N1)pdm09 vaccines for preventing reverse transcription polymerase chain reaction-confirmed pandemic influenza hospitalizations: case-control study of children and adults at 10 US influenza surveillance network sites.
During 2009-2010, we examined 217 patients hospitalized with laboratory-confirmed pandemic influenza in 9 Influenza Hospitalization Surveillance Network sites and 413 age- and community-matched controls and found that a single dose of monovalent nonadjuvanted influenza A(H1N1)pdm09 vaccine was 50% (95% confidence interval, 13%-71%) effective in preventing hospitalization associated with A(H1N1)pdm09 virus infection.


Attentional capture during attentional awakening.
We investigated whether attentional set is available at the beginning of a trial or whether it develops gradually within a trial. Thus, we manipulated the time from the onset of a trial to a target and observers' search strategy. We also observed the effect of the presence or absence of distractors as an index of the temporal development of attentional set. Participants identified a target letter embedded in a stream of rapidly presented nontargets while ignoring peripheral distractors. Baseline accuracy when no peripheral distractor was presented increased as the target appeared later in the stream, suggesting attentional awakening. Identification accuracy was impaired by the presence of peripheral distractors (i.e., attentional capture) early in the stream only when observers adopted the feature search mode. The magnitude of attentional capture increased over the course of the first 1,000 ms of a trial under the singleton detection and feature search modes. These results suggest that singleton detection mode requires time for a bottom-up signal to be effective in capturing attention, whereas the feature search mode does not require such a warm-up period to be effective and is available from the beginning of viewing the stream.


Attitudes towards menstruation: what women want? An Italian National Survey.
Many women experience negative feelings during menstrual bleeding. Aim of the study was to evaluate the attitudes of Italian women towards menstrual bleeding, their desire to reduce its frequency and knowledge of the existence of methods capable of achieving such an objective. An internet-based anonymous questionnaire has been sent to women willing to fill it in through different social media (Instagram, WhatsApp, Facebook, Twitter). The survey evaluated, objective parameters such as number of pads, use of painkillers, duration of period and pain intensity. Judgement towards period and knowledge about methods to reduce frequency and amount of menstrual flow were analysed. 1072 Women aged 18 - 40 years, answered the survey. The level of education of responders was high, with 61.7% having a university degree. 27.5% of respondents viewed positively the occurrence of a menstrual period. Ideal frequency of menstrual cycles was considered 3 months and the perfect duration was considered to be 3 days. Half of the respondents ignored the existence of methods to suppress menstruation or reduce its frequency. 52% of participants stated that they would not use a contraceptive method because they considered it not 'natural'. In our sample, in spite of the discomfort reported by half of the women interviewed, menstruation was considered positively by one fourth as because confirm their fertility. The majority of women did consider bleeding every month a healthy, but they preferred a three-monthly frequency. Knowledge of contraceptive methods capable of reducing the frequency of menstrual bleeding was scarce.


Boundedness of Marcinkiewicz integrals with rough kernels on Musielak-Orlicz Hardy spaces.
Let [Formula: see text] satisfy that [Formula: see text], for any given [Formula: see text], is an Orlicz function and [Formula: see text] is a Muckenhoupt [Formula: see text] weight uniformly in [Formula: see text]. The Musielak-Orlicz Hardy space [Formula: see text] is defined to be the set of all tempered distributions such that their grand maximal functions belong to the Musielak-Orlicz space [Formula: see text]. In this paper, the authors establish the boundedness of Marcinkiewicz integral [Formula: see text] from [Formula: see text] to [Formula: see text] under weaker smoothness conditions assumed on Ω. This result is also new even when [Formula: see text] for all [Formula: see text], where ϕ is an Orlicz function.


Comparative evaluation of the modified Scarff-Bloom-Richardson grading system on breast carcinoma aspirates and histopathology.
Fine needle aspiration (FNA) is a quick, minimally invasive procedure for evaluation of breast tumors. The Scarff-Bloom-Richardson (SBR) grade on histological sections is a well-established tool to guide selection of adjuvant systemic therapy. Grade evaluation is possible on cytology smears to avoid and minimize the morbidity associated with overtreatment of lower grade tumors. The aim was to test the hypothesis whether breast FNA from the peripheral portion of the lesion is representative of Scarff-Bloom-Richardson grade on histopathology as compared to FNA from the central portion. Fine-needle aspirates and subsequent tissue specimens from 45 women with ductal carcinoma (not otherwise specified) were studied. FNAs were performed under ultrasound guidance from the central as well as the peripheral third of the lesion for each case avoiding areas of necrosis/calcification. The SBR grading was compared on alcohol fixed aspirates and tissue sections for each case. Comparative analysis of SBR grade on aspirates from the peripheral portion and histopathology by the Pearson chi-square test (χ(2) =78.00) showed that it was statistically significant (P<0.001) with 93% concordance. Lower mitotic score on aspirates from the peripheral portion was observed in only 4 out of 45 (9%) cases. The results of the Pearson chi-square test (χ(2) = 75.824) with statistically significant (P=0.000). This prospective study shows that FNA smears from the peripheral portion of the lesion are representative of the grading performed on the corresponding histopathological sections. It is possible to score and grade by SBR system on FNA smears.


Endoplasmic reticulum remodeling induced by Wheat yellow mosaic virus infection studied by transmission electron microscopy.
Plant virus was a kind of organism lived depending on infecting viable host cell and propagated their posterity by replicating its hereditary nucleotide, transcripting into protein, assembling protein and nucleotide into virion (Ortín and Parra, 2006; Sanfaçon, 2005). Viral infection usually induces remodeling of host cell, especially endoplasmic reticulum (ER) for generating membrane packed viral factory. During the infection of Bymovirus, a kind of membranous body (MB) was generated in host cells, which is thought as an ER aggregate. In present study we performed a study on Wheat yellow mosaic virus (WYMV) induced MB by several transmission electron microscopy (TEM) based methods, including cytological observation, component analysis by immuno-gold labeling and structural analysis by electron tomography (ET). WYMV infection induced at least two morphologies of MB, including the lamella dominated morphology (lamella-MB) looked like sprawling cirrus, and the tubule dominated morphology (tubule-MB) looked like latticed network. MB was verified composing of ER as revealed by immuno-gold labeling by antibody against endoplasmic reticulum (ER) retention signal as well as by detailed observation of MB construction modules as double layer membrane. By immuno-gold labeling, both two MB morphologies (lamella-MB and tubule-MB) had same components in viral derived protein and membrane origination (from ER). Structural analysis by ET reconstruction revealed the organization of ER in MB. Lamella-MB was composed of cesER like structures arranged irregularly whereas tubule-MB was composed of tubER like structures arranged regularly. This study provided insights into the structural details in how Bymovirus utilizing host membrane system.


Making and breaking carbon-carbon bonds in class C radical SAM methyltransferases.
Radical S-adenosylmethionine (SAM) enzymes utilize a [4Fe-4S]1+ cluster and S-(5'-adenosyl)-L-methionine, (SAM), to generate a highly reactive radical and catalyze what is arguably the most diverse set of chemical reactions for any known enzyme family. At the heart of radical SAM catalysis is a highly reactive 5'-deoxyadenosyl radical intermediate (5'-dAdo●) generated through reductive cleavage of SAM or nucleophilic attack of the unique iron of the [4Fe-4S]+ cluster on the 5' C atom of SAM. Spectroscopic studies reveal the 5'-dAdo● is transiently captured in an FeC bond (Ω species). In the presence of substrate, homolytic scission of this metal‑carbon bond regenerates the 5'-dAdo● for catalytic hydrogen atom abstraction. While reminiscent of the adenosylcobalamin mechanism, radical SAM enzymes appear to encompass greater catalytic diversity. In this review we discuss recent developments for radical SAM enzymes involved in unique chemical rearrangements, specifically regarding class C radical SAM methyltransferases. Illuminating this class of radical SAM enzymes is especially significant as many enzymes have been shown to play critical roles in pathogenesis and the synthesis of novel antimicrobial compounds.


[Preclinical care of children with multiple trauma].
Severe multiple trauma in children is rare with approximately 380-550 cases per year in Germany. In addition to the S3 guideline "Polytrauma", which was published more than a decade ago, the S2K guideline "Severe multiple trauma care in childhood" was published in 2020. Accidents and especially the resulting traumatic brain injuries still represent the most frequent cause of death in children. While prehospital treatment according to Prehospital Trauma Life Support (PHTLS®) is basically analogous to that in adults which is based on the ABCDE concept (airway, breathing, circulation, disability, exposure), knowledge of age-dependent anatomical-physiological characteristics is essential. For simplification, various tools and dosing aids, such as the pediatric emergency ruler and specific emergency tables, are available. Further treatment after initial preclinical care should take place in an interdisciplinary manner in designated pediatric trauma centers.


Cell-mediated mutagenesis in cultured Chinese hamster cells by carcinogenic polycyclic hydrocarbons: nature and extent of the associated hydrocarbon-DNA reaction.
A system of cell-mediated mutagenesis is described for the study of compounds which require metabolic activation to exert their cytotoxic and mutagenic effects. This system combines BHK21 cells for metabolism of the compounds and V79 cells as targets for mutagenesis. Using the two polycyclic hydrocarbon carcinogens benzo(a)pyrene and 7-methylbenz(a)anthracene we have shown that the hydrocarbon-DNA reaction which accompanies mutagenesis in the target cell is indistinguishable from that reported to occur in vivo and in primary cell cultures. Our results also support the view that a diol epoxide metabolite is responsible for the biological activity of benzo(a)pyrene. The application of cell-mediated mutagenesis to the routine testing of suspect environmental chemicals for biological activity is discussed.


Pediatric proximal tibial fractures: How does the trauma mechanism guide the operative strategy?
Pediatric proximal tibial fractures (PTF) are rare but potentially debilitating. So far, no system for guiding surgical treatment based on injury-force mechanism has been documented, while adult tibial plateau fractures have benefited greatly from such an approach. This study reviews the diagnosis and treatment experience at a tertiary trauma center and introduces the reduction-traction method. Pediatric patients (0-17 years old) diagnosed with PTF were identified in the hospital database from 2017 to 2021. Their injury mechanism, injury location, treatment type, and treatment outcomes were recorded. Images were reviewed to establish an injury-force classification according to Mubarak et al., 2009. When appropriate, patients were treated using a "reduction-traction" approach. Twenty-nine patients were identified, and followed-up for a mean of 6.8 months. The most common cause of injury was falling from height < 2 m, often from a trampoline. The tibial plateau and proximal tibial metaphysis were most commonly involved. Thirteen patients were treated non-operatively, 10 with open reduction and internal fixation, and six with arthroscopic surgery. A bimodal distribution according to age was noted in the injury mechanism, injury site, and treatment type. No adverse outcomes were recorded, and all patients resumed sports activities. The "reduction-traction" technique produced favorable outcomes in three patients. Pediatric PTF has a bimodal distribution with high risk before three years and after 15 years. The injury-force classification can supplement the Salter-Harris classification in guiding surgical treatment. The "reduction-traction" approach in children differs from adults, and results in good outcomes.


Accumulation and time trends (2003-2015) of persistent organic pollutants (POPs) in blubber of finless porpoises (Neophocaena asiaeorientalis) from Korean coastal waters.
Accumulation of persistent organic pollutants (POPs) in marine mammals is of great concern and is associated with declining populations. The concentrations of polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and polybrominated diphenyl ethers (PBDEs) were measured in blubber of finless porpoises (Neophocaena asiaeorientalis) collected from Korean coastal waters in 2010 and 2015, to assess the concentrations, time trends, and ecotoxicological effects. Among the POPs measured, DDTs were detected at the highest concentrations, followed by PCBs and PBDEs. Significant age- and sex-dependent accumulation of POPs was evident for porpoises collected in 2010, but not for those collected in 2015. This finding may be a function of stabilization of POP concentrations over time. In our study, accumulation patterns of POPs were dependent on consumption patterns and physico-chemical properties of the contaminants, and on the metabolism in the porpoises. Significant reductions of POPs were found between 2003 and 2010, likely reflecting the impact of domestic and global regulation of POPs. However, no changes in most POPs were found between 2010 and 2015, suggesting a trend toward stabilization. Approximately 10 % and 27 % of porpoises exceeded previously proposed threshold levels for PCBs and DDTs, respectively, implying a potential health risk.


Rate-limiting effects of Cyclin D1 in transformation by ErbB2 predicts synergy between herceptin and flavopiridol.
Cyclin D1 is downstream of erbB2 and is required for erbB2 transformation. Here we report thatcyclin D1 functions are essential, rate limiting for erbB2 transformation, and reciprocally increase erbB2 levels. This interaction depends on three cyclin D1 activities: cyclin-dependent kinase 4-dependent kinase activity, titration of p27, and an intrinsic transcriptional activity of cyclin D1. Drugs active against erbB2 and cyclin D1 (Herceptin and flavopiridol) were synergistically cytotoxic against erbB2-positive breast cancer cell lines. Addition of flavopiridol to Herceptin synergistically lowered erbB2 levels in these cells. Our data suggest the potential use of combinations of cyclin-dependent kinase inhibitors and Herceptin in breast cancer.


Antisense RNA targeting of primase interferes with bacteriophage replication in Streptococcus thermophilus.
The putative primase gene and other genes associated with the Sfi21-prototype genome replication module are highly conserved in Streptococcus thermophilus bacteriophages. Expression of antisense RNAs complementary to the putative primase gene (pri3.1) from S. thermophilus phage kappa 3 provided significant protection from kappa 3 and two other Sfi21-type phages. Expression of pri3.10-AS, an antisense RNA that covered the entire primase gene, reduced the efficiency of plaquing (EOP) of kappa 3 to 3 x 10(-3) and reduced its burst size by 20%. Mutant phages capable of overcoming antisense inhibition were not recovered. Thirteen primase-specific antisense cassettes of different lengths (478 to 1,512 bp) were systematically designed to target various regions of the gene. Each cassette conferred some effect, reducing the EOP to between 0.8 and 3 x 10(-3). The largest antisense RNAs (1.5 kb) were generally found to confer the greatest reductions in EOP, but shorter (0.5 kb) antisense RNAs were also effective, especially when directed to the 5' region of the gene. The impacts of primase-targeted antisense RNAs on phage development were examined. The expression of pri3.10-AS resulted in reductions in target RNA abundance and the number of phage genomes synthesized. Targeting a key genome replication function with antisense RNA provided effective phage protection in S. thermophilus.


Stability of recombinant human alpha-1-antitrypsin produced in rice in infant formula.
Human milk contains several biologically active proteins that benefit the breast-fed infant. In order to survive in the gastrointestinal tract, these proteins need to be protected against proteolysis. Since human milk contains relatively high concentrations of alpha-1-antitrypsin (AAT), we have expressed recombinant AAT in rice to explore the possibility of supplementing infant formula with this protein. The stability of recombinant AAT was examined by biochemical and functional assays, such as SDS-PAGE, Western blotting, ELISA, elastase and trypsin inhibition, following exposure to heat, low pH, and in vitro digestion, conducted in both phosphate buffered saline and infant formula. Native AAT is resistant to acidic environments down to pH 2 for 1 h and can withstand in vitro digestion modeled after conditions in the infant gut. Recombinant AAT is nearly as resistant as the native form in buffer, and is equally resilient in formula. Heat treatments (60 degrees C for 15 min, 72 degrees C for 20 sec, 85 degrees C for 3 min, and 137 degrees C for 20 sec) revealed that recombinant AAT is not as stable as native AAT in buffer, particularly at higher temperatures. While significantly less recombinant AAT is detected by ELISA after heating in formula, addition of bile extract can restore epitopes resulting in higher concentrations, suggesting protein aggregation that may not affect AAT activity. This study shows that recombinant AAT may survive the conditions of the infant stomach and duodenum and affect protein digestion in the infant small intestine.


Intersectional Inequalities and Individual Heterogeneity in Chronic Rheumatic Diseases: An Intersectional Multilevel Analysis.
To examine how intersections of multiple sociodemographic variables explain the individual heterogeneity in risk of being diagnosed with any of following chronic rheumatic diseases (CRDs): osteoarthritis (OA), gout, rheumatoid arthritis (RA), or spondyloarthritis (SpA). We identified individuals ages 40-65 years residing in Skåne, Sweden by December 31, 2013 and having done so from January 1, 2000 (n = 342,542). We used a Skåne health care register to identify those with a diagnosis of the CRD of interest between January 1, 2014 and December 31, 2015, with no previous such diagnosis during 2000-2013. We created 144 intersectional social strata (ISS) using categories of age, sex, education, income, civil status, and immigration. For individuals nested within ISS, we applied multilevel logistic regression models to estimate the variance partition coefficient (VPC) as a measure of discriminatory accuracy of the ISS and the predicted absolute risks and 95% credible intervals for each stratum. Overall, 3.5%, 0.5%, 0.2%, and 0.2% of the study population were diagnosed with OA, gout, RA, and SpA, respectively. The VPC ranged from 16.2% for gout to 0.5% for SpA. Sex explained the largest proportion of between-strata variation in risk of RA, gout, and SpA, while age was the most important factor for OA. The most between-strata differences in risk of these CRDs were due to the additive main effects. Despite meaningful between-strata inequalities in the risk of being diagnosed with CRDs (except SpA), there were substantial within-strata heterogeneities that remain unexplained. There was limited evidence of intersectional interaction effects.


Dietary lipids and geriatric depression scale score among elders: the EPIC-Greece cohort.
In a prospective epidemiological investigation aiming to identify dietary lipids potentially associated with affective state and depression, 610 healthy men and women aged 60 years or older, participating in the EPIC-Greece cohort and residing in the Attika region had dietary, sociodemographic, anthropometric, medical and lifestyle variables ascertained at enrollment. Six to 13 years later, affective state was evaluated through the 15-point geriatric depression scale (GDS) score along with cognitive function and medical variables. In multivariate linear regression analysis, while adjusting for potential confounders, GDS score was negatively associated with dietary intake of monounsaturated lipids (MUFA) and their main source, olive oil, and positively associated with intake of polyunsaturated lipids (PUFA) and one of their principal sources, seed oils. Intake of calories, total lipids, fish and seafood or saturated lipids did not exhibit significant association with GDS. Potential non-linearities were assessed by quantile multivariate regression analysis: The median GDS score was positively associated with PUFA and seed oils intake, while other lipid groups showed no appreciable associations. The 90th percentile of the GDS score (towards the high end) exhibited significant negative associations with MUFA and olive oil, weaker positive associations with PUFA and seed oils and no appreciable association with other lipid group dietary intakes. We conclude that among Attika elders, lower intake of seed oils and higher intake of olive oil prospectively predict a healthier affective state. Olive oil intake, in particular, predicts a lower chance of scoring in the highest part of the GDS.


The use of PrEP among men who have sex with men and transgender women as Biomedical Prevention Work: A conceptual framework.
Based on ethnographic fieldwork among men who have sex with men and transgender women in Tanzania, this article explores the various types of work that may go into enrolment into PrEP programming and using pre-exposure prophylaxis (PrEP). PrEP protects against HIV acquisition and is widely touted as an essential tool in 'ending AIDS by 2030'. While taking PrEP has often been portrayed as 'just taking a pill a day' in public health campaigns, a striking observation during fieldwork was that enrolling in PrEP programming and adhering to PrEP involved a wide range of tasks. Inspired by this fieldwork experience and the literature on sociology of work, more specifically illness work and patient work, we started to think of these tasks as work. This paper identifies the range of tasks that PrEP users in Dar es Salaam had to perform as part of their enrolment and usage of PrEP. We provide a description of these tasks, organised into three categories of work that we refer to as (a) readying work, (b) user work, and (c) social navigation work that jointly make up what we propose to call biomedical prevention work. We further suggest that this analytical framework can be applicable to other biomedical prevention methods in other contexts.


Lung clearance and disposition of 63Ni in F344/N rats after intratracheal instillation of nickel sulfate solutions.
Epidemiology studies have indicated increased incidences of respiratory tract and renal cancer in nickel refinery workers. Since the most likely route of exposure to nickel in the workplace is via the respiratory tract, the objectives of the experiments described here were to determine the retention pattern of Ni in the lungs, identify the target organs for Ni absorbed from the respiratory tract, and determine rates for excretion of Ni. Male and female F344 rats were given 17, 190, or 1800 nmoles Ni (as a nickel sulfate solution) in saline, containing trace amounts of 63Ni, by intratracheal instillation. Urine and feces were collected, and rats were necropsied at predetermined times up to 96 hr after instillation. At all times, lungs, trachea, larynx, kidney, and urinary bladder contained the highest concentrations of Ni as determined by liquid scintillation spectrometry. Urine was the major route for excretion of Ni, accounting for 50% of the dose after instillation of 17 or 190 nmoles Ni, and 80% of the dose after instillation of 1800 nmoles Ni. The half-time for urinary excretion of Ni increased from 4.6 hr at the highest dose to 23 hr at the lowest dose used. Fecal excretion accounted for 30% (17- and 190-nmole doses) or 13% (1800 nmoles) of the initial dose. Of the Ni remaining in the body at the end of 96 hr, over 50% was in the lungs. The long-term half-time for clearance of Ni from the lungs ranged from 21 hr at the highest dose to 36 hr at the lowest dose instilled. As the amount of instilled Ni decreased, the fraction of the instilled Ni associated with the long-term clearance component increased (from 24% at the highest dose to 40% at the lowest dose). Results suggest that, over the range of doses studied, both pulmonary clearance of Ni and routes for excretion of Ni were dependent on the instilled dose.


Chronic toxicity/carcinogenicity study of trans-anethole in rats.
A chronic feeding study was carried out in rats with trans-anethole. The test substance was administered in the diet to groups (n = 26-78) of 312 male and 312 female Sprague-Dawley rats at concentrations of 0, 0.25, 0.5 and 1% for 117-121 wk. The average intakes of trans-anethole varied from 105-550 mg/kg body weight/day. No apparent treatment-related reactions were noted. The only effect was a transient retardation of body-weight gain. No excess mortality was caused by the treatment. No abnormalities related to treatment were seen on necropsy except for reduced adiposity in the highest dose groups. Haematological assessments did not reveal any changes related to treatment. Histological examination revealed certain non-neoplastic and neoplastic lesions common in older rats. The incidence of some hepatic lesions was significantly higher in some treated groups than in controls: altered cell foci (females of the 1% group), nodular hyperplasia (males of the 0.5% group and males and females of the 1% groups), benign tumours (females of the 1% group) and malignant tumours (females of the 1% group). The results are compared with those of previous investigations. The authors of this study stress that the low incidence of hepatocarcinomas is restricted to a single species and sex and to the highest dose tested. This pattern of species, sex and dose dependency strongly suggests that metabolic and pharmacokinetic studies will be helpful in interpreting the significance of the rat tumours with regard to the safe consumption of trans-anethole by man. The changes observed in this chronic feeding study are not thought to be of genetic origin and consequently trans-anethole does not constitute a significant carcinogenic risk to man. Further studies are in progress to substantiate this conclusion.


T-helper-associated cytokines expression by peripheral blood mononuclear cells in patients with polypoidal choroidal vasculopathy and age-related macular degeneration.
Immune responses play a key role in the pathogenesis and progression of polypoidal choroidal vasculopath (PCV) and age-related macular degeneration (AMD). In this study, we determined the Th cell-associated immune responses by measuring the cytokine expression of peripheral blood mononuclear cells (PBMC) in both PCV and neovascular AMD (nAMD) patients. Twenty-seven nAMD patients, 33 PCV patients and a gender- and age-matched group of 18 healthy individuals were involved in this study. The Th-cell cytokine profiles including levels of interferon-gamma (INF-γ), interleukin (IL)-17A and IL-4 in cultures of PBMCs were determined by enzyme-linked immunosorbent assay (ELISA). IFN-γ,IL-17A and IL-4 production was significantly increased after stimulation with PHA. The levels of IFN-γ and IL-4 in PHA-stimulated cultures were higher in PCV and nAMD patients than that in healthy controls (P = 0.038,P = 0.014), while no difference was found between PCV and nAMD (all P > 0.05). No significant difference in IL-17A level in PHA-stimulated cultures was found among PCV, nAMD and control groups (P > 0.05). These findings suggest that circulating IFN-γ and IL-4 producing Th1 and Th2 cells may involve in the pathogenesis of PCV and nAMD. PCV may have the similar immune responses with nAMD.


Generation of an induced pluripotent stem cell line from an Ohtahara syndrome patient with the hemizygous mutation p.Q503Afs*28 (c.1507_1508del) in the ARX gene.
Aristaless-related homeobox (ARX)-related disorders are recessive X-linked intellectual disability disorders. We encountered a patient with a hemizygous mutation (c.1507_1508del) showing intellectual disability, early-onset epileptic encephalopathy and Ohtahara syndrome. The patient had female genitals, but an XY karyotype. We established an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a six-month Chinese child with a hemizygous mutation (c.1507_1508del) in ARX. The PBMCs were reprogrammed with Sendai viral vectors. The iPSCs showed stable amplification, pluripotency-related gene expression, and trilineage differentiation potential. Karyotype analysis of the iPSCs showed 23 pairs of chromosomes with normal structure and sex chromosome is XY.


Bronchoscopy Laser and Silicone Y-Stents as Emergency Airway Management in Central Airway Stenosis Due to Secondary Thyroid Carcinoma: A Case Report.
Total airway obstruction in thyroid cancer is rare and has high morbidity and mortality. Airway management in such cases is challenging, especially in cases in which thyroid masses cannot be totally resected. It is important to choose the appropriate airway treatment modality. Currently, therapeutic rigid bronchoscopy procedures and endoluminal lasers, as well as airway stent insertion, are a management modality of near-total malignant airway obstruction. We report a rigid bronchoscopy procedure combined with laser and Y-stent silicone insertion in thyroid cancer with extension infiltration, as well as compression in the trachea covering the subglottic tracheal area up to the main carina and tracheo-bronchomalacia, manifesting as acute respiratory failure.


A sub-chronic toxicity evaluation of a natural astaxanthin-rich carotenoid extract of Paracoccus carotinifaciens in rats.
Astaxanthin is believed to be beneficial to human health because it possesses strong antioxidant properties. A natural astaxanthin-rich carotenoid extract (ARE) was produced by a well-controlled fermentation of a natural bacteria Paracoccus carotinifaciens, followed by the extraction and enrichment of the final product comprising mixture of carotenoids that is predominantly astaxanthin. The aim of this study was to evaluate the sub-chronic toxicity of the ARE using 6 week old Sprague-Dawley SPF rats [Crl:CD(SD)]. The test article was suspended in olive oil and administered daily to the rats by oral gavage for 13 weeks at doses of 0 (olive oil), 250, 500 or 1000 mg/kg/day. Each group consisted of 10 animals of each sex. No deaths occurred and no treatment-related changes were observed in the detailed clinical observations, manipulative tests, grip strength, motor activity, body weights, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology. Dark-red feces were observed throughout the administration period in all treated groups due to excretion of the colored test article. Based on these results, it was concluded that the no observed adverse effect level (NOAEL) for ARE was at least 1000 mg/kg/day for male and female rats, respectively.


A Study to Inform the Design of a National Multicentre Randomised Controlled Trial to Evaluate If Reducing Serum Phosphate to Normal Levels Improves Clinical Outcomes including Mortality, Cardiovascular Events, Bone Pain, or Fracture in Patients on Dialysis.
Background. Retrospective, observational studies link high phosphate with mortality in dialysis patients. This generates research hypotheses but does not establish "cause-and-effect." A large randomised controlled trial (RCT) of about 3000 patients randomised 50 : 50 to lower or higher phosphate ranges is required to answer the key question: does reducing phosphate levels improve clinical outcomes? Whether such a trial is technically possible is unknown; therefore, a study is necessary to inform the design and conduct of a future, definitive trial. Methodology. Dual centre prospective parallel group study: 100 dialysis patients randomized to lower (phosphate target 0.8 to 1.4 mmol/L) or higher range group (1.8 to 2.4 mmol/L). Non-calcium-containing phosphate binders and questionnaires will be used to achieve target phosphate. percentage successfully titrated to required range and percentage maintained in these groups over the maintenance period. Secondary endpoints: consent rate, drop-out rates, and cardiovascular events. Discussion. This study will inform design of a large definitive trial of the effect of phosphate on mortality and cardiovascular events in dialysis patients. If phosphate lowering improves outcomes, we would be reassured of the validity of this clinical practice. If, on the other hand, there is no improvement, a reassessment of resource allocation to therapies proven to improve outcomes will result. Trial Registration Number. This trial is registered with ISRCTN registration number ISRCTN24741445.


The energetics of muscle contractions resembling in vivo performance.
Muscle energetics has expanded into the study of contractions that resemble in vivo muscle activity. A summary is provided of experiments of this type and what they have added to our understanding of muscle function and effects of compliant tendons, as well as the new questions raised about the efficiency of energy transduction in muscle.


Educators' perceptions of their experiences of transnational education in nursing: A grounded theory study.
The study aim was to explore educators' perceptions of their experiences of participating in transnational education in nursing. In an increasingly globalised world, involvement with the delivery of transnational education has become commonplace across the international higher education sector. In recent years, transnational education within the academic discipline of nursing has developed at pace, evolving in response to a global need to invest in nurse education, address nursing shortages and strengthen nursing leadership. However, despite acknowledgement that transnational education is a complex activity that needs to be more fully understood, research specifically exploring transnational education in nursing is scarce, as previous studies predominantly focus on other academic disciplines. The study addresses this knowledge gap, advancing understanding of transnational education in the context of nursing. The study was positioned within the interpretivist paradigm and underpinned by a constructivist grounded theory methodological design, acknowledging the prior knowledge and experience of the research team in relation to phenomenon under investigation. Ethical approval was obtained before the study commenced, ensuring adherence to key ethical principles. The study was conducted during May to August 2020, in a university in the North of England that provides undergraduate and postgraduate nurse education in the United Kingdom and transnational context. Participants were recruited via e mail and invited to complete a brief questionnaire, informing a preliminary theoretical sampling strategy. Ten educators with experience of transnational education across a diverse range of international locations participated in individual, semi-structured, online interviews that were recorded and transcribed verbatim. Data were analysed using initial and focused coding, constant comparison, theoretical memos and diagrams. The findings uncovered three overarching data categories, each of which were crucial to supporting effective transnational education in nursing. Prepare- involved developing an understanding of the context of healthcare and education, being supported and collaborating with transnational partners. Perform- involved recognising language and cultural influences, adapting to the environment and implementing responsive educational pedagogies. Progress- involved recognition of personal development at individual level and valuing the benefits at organisational level. Although transnational education in nursing can be challenging and complex, it can offer worthwhile advantages for all stakeholders. However, effective transnational education in nursing is dependent on strategies which prepare educators appropriately and enable them to perform effectively, thereby promoting successful outcomes at individual, organisational and transnational partner level and facilitating advancement in future potential collaborative activity.


Technique using a percutaneous nephroscope and nephroscopic scissors transurethrally for treatment of complicated orthotopic ureterocele in adult women.
To present an endoscopic technique for the decompression of complicated orthotopic ureterocele in adult women. Five women with complicated orthotopic ureterocele were evaluated in the present study. The ureterocele was complicated by stones in 2 patients and urinary tract infection in 4. An endoscopic technique was used for the treatment of these ureteroceles. A 26F rigid nephroscope was placed into the bladder. When the ureterocele was seen in the bladder, the nephroscopic scissors was advanced through the nephroscopic channel to the ureterocele. A puncture was made on the anterior wall of the ureterocele using the nephroscopic scissors. Next, a ureteral catheter was introduced to puncture the ureterocele. Next, a window approximately 5-10 mm in diameter was opened on the wall of the ureterocele using the nephroscopic scissors. Finally, a double-J stent and urethral catheter were placed. The stones were fragmented using a pneumatic lithotripter. All the patients were evaluated with urinalysis, urine culture, ultrasonography, and voiding cystourethrography at the third month postoperatively. The mean procedure time was 18.4 minutes. No complication was observed during the procedure, except for mild hematuria. The mean postoperative hospital stay was 19.8 hours. All patients with stones were stone free after the procedure. No cases of postoperative urinary tract infection developed. None of these patients had de novo reflux or obstruction at 3 months postoperatively. This technique could be an alternative treatment option for decompression of complicated orthotopic ureterocele in adult women.


Centre of pressure error with increasing gait velocity: The clinical impact on predicted inverse dynamics during gait in children with typical development.
Centre of pressure (CoP) location error is common when predicting inverse dynamic parameters during gait. Tolerance levels of error have been previously reported. However, the clinical impact of gait velocity on CoP error has not been considered. What is the clinical impact of CoP error with increasing gait velocity on predicted inverse dynamic parameters during gait in children with typical development? Three-dimensional kinematic and kinetic data were recorded at three self-selected velocities on children with typical development (walking, fast instructed walking and running). CoP location error was applied in 3 mm increments up to a maximum of 12 mm in an anteroposterior direction. Differences in maximum kinetic parameters between increments and gait velocities were assessed in conjunction with changes in GDI-kinetic. Relative error (difference expressed as a % of maximum moment) decreased at all joints as gait velocity increased. The GDI-kinetic was only clinically significant for the self-selected walking condition at 9 mm and 12 mm respectively. The GDI-kinetic difference remained below the threshold for fast walking and running which suggested that CoP error of up to 12 mm in the 3D optoelectric / force plate configuration would be acceptable if subjects were assessed under these conditions.


Prescription for antiresorptive therapy in Mexican patients with rheumatoid arthritis: is it time to reevaluate the strategies for osteoporosis prevention?
Glucocorticoids are frequently used in rheumatoid arthritis (RA) in order to alleviate symptoms of joint inflammation, retard erosions and to treat extra-articular manifestations, although these drugs may increase the risk of bone mineral loss and osteoporotic fractures. To date, in Mexico there are no studies that identify the frequency of patients with RA with corticosteroids, receiving therapy for osteoporosis. Therefore, we evaluated the prevalence and factors related to the prescription of antiresorptives in 520 Mexican patients with RA. We used a multivariate model to identify variables associated with antiresorptives prescription. We identified that although 79% of patients were under treatment with glucocorticoids, only 13% received antiresorptive agents as preventive therapy for osteoporosis. The multivariate analysis identified that higher proportions of antiresorptive drugs prescriptions were associated with female patients (OR 11.40, 95% CI: 1.5-84.3, P = 0.02), an age of 40 years or more (OR 3.22, 95% CI: 1.3-8.3, P = 0.02) and to consume a lower number of cointerventions with other drugs (OR 1.09, 95% CI: 1.0-1.2, P = 0.03). Corticosteroid treatment was not associated with the prescription of antiresorptives (P = 0.31). In conclusion, a low proportion of Mexicans with RA receive antiresorptive therapy independently regardless of whether they consume or not chronically corticosteroids. Additional strategies should be evaluated to encourage the prevention and early treatment for osteoporosis in patients with RA.


Solute--water interactions: do polyhydroxy compounds after the properties of water?
The interactions between PHCs and water, like those between water molecules, are governed by hydrogen bonding. The details of these interactions are very sensitive to spacings and orientations of the -OH groups on the solute molecules. Where different conformers can coexist in solution, the aqueous solvent acts so as to favor the conformer with the largest number of equatorial -OH groups, because of their spatial compatibility with water. Because of this compatibility, aqueous solutions of PHCs have the tendency to supersaturation and incomplete freezing, manifestations of the phenomenon known as bound water which is, however, a misnomer. The range of water structure perturbation is probably governed by hydration forces which appear to dominate at solute-solute distances of less than 3 nm and which decay exponentially. Although on a single hydrogen bond basis the hydration effects are marginal, they nevertheless are responsible for many macroscopic phenomena, e.g., gel formation, liquid crystals, and protection against dehydration.


[In vitro study on Hep G2 cell infected by hepatitis C virus].
To establish hepatitis C virus (HCV) infected cell model which is similar to the infection in vivo and can support HCV to replicate for a long time. After infected with HCV-positive serum, Hep G2 cells were cultured for 60 days. Nested RT-PCR was used to detect plus and minus HCV RNA in cultured cells and supernatants. Plus HCV RNA was detected intermittently in Hep G2 cells during 2-30 days, minus HCV RNA was detected during 3-30 days after infection, the detection rate was similar to plus HCV RNA. Plus and minus HCV RNA can be still intermittently detected during 31-60 days after infection. However, the detection rate gradually declined. Plus HCV RNA was also found intermittently positive in the supernatant, and the detection rate was consistent to that in cells. Minus HCV RNA was not detected in the supernatant. Hep G2 cells were susceptible to HCV, and could support HCV to replicate for a relatively long time. Hep G2 is an ideal HCV infection cell model.


Physical Health Screenings Among African-American Church and Community Members.
This study sought to identify characteristics, including religiosity, related to having received health screenings among persons who attend African-American churches or receive church-based community outreach services. A sample of 602 was recruited during two phases as part of a larger project. Blood pressure, cholesterol, and blood glucose screenings were the most frequently reported screenings ever and in the last 12 months. Although religiosity was significantly related to several of the health screenings in bivariate analysis, it is not a predictor of health screenings in multivariate analyses. Innovative strategies are needed to promote screenings such as church-based health fairs.


Determination of diastereoisomers of bromadiolone, an anticoagulant rodenticide, in animal tissues by high-performance liquid chromatography.
Two components isolated by semi-preparative normal phase high-performance liquid chromatography (HPLC) of bromadiolone reference material were tentatively identified as diastereoisomeric forms. Examination by mass spectroscopy confirmed this identification and supporting evidence was provided by identical UV fluorescence characteristics. The separated isomers were used to examine the chromatographic properties of bromadiolone in ion-pair, ion-suppression and weak ion-exchange HPLC modes. Conditions suitable for the analytical determination of the individual diastereoisomers were established for each mode. The influence of mobile phase pH on the resolution of coumarin-based rodenticides by weak ion-exchange HPLC on an aminopropyl-bonded phase was studied. Clean-up techniques for the determination of residues of bromadiolone in animal tissue extracts were compared. A combined gel permeation and adsorption chromatographic procedure was preferred for sensitive assay; it permitted the use of either fluorescence or UV detection. The lower practical limit of determination of each isomer in animal tissues was 0.005 mg kg-1 using UV detection and 0.0005 mg kg-1 using fluorescence detection.


Immobilization and hybridization of oligonucleotides on maleimido-terminated self-assembled monolayers.
Maleimido-terminated self-assembled monolayers were prepared via a one-step reaction of a maleimido-functionalized trichlorosilane with an oxide-covered surface. Through conjugate addition, thiol-tagged DNA was immobilized on these maleimido-functionalized self-assembled monolayers, and these immobilized oligonucleotides were further hybridized with complementary strands. The surface concentrations of oligonucleotides were quantified with radioactivity measurements. The surface concentrations of immobilized oligonucleotides increase in a nonlinear manner with increasing molar fraction of maleimido moieties on the surface and achieve high values of 1.6 (+/-0.6) x 10(13) oligonucleotides/cm2 if monolayers having full coverage of maleimido groups are used. High hybridization efficiencies of complementary strands (approximately 75%) are obtained even if the surface concentration of immobilized strands exceeds a value of 5.0 x 10(12) oligonucleotides/cm2. Furthermore, five cycles of denaturation and rehybridization result in only a 4% loss of the immobilized DNA after each run.


Use of a temporary immersion bioreactor system for the sustainable production of thapsigargin in shoot cultures of Thapsia garganica.
Thapsigargin and nortrilobolide are sesquiterpene lactones found in the Mediterranean plant Thapsia garganica L. Thapsigargin is a potent inhibitor of the sarco/endoplasmic reticulum calcium ATPase pump, inducing apoptosis in mammalian cells. This mechanism has been used to develop a thapsigargin-based cancer drug first by GenSpera and later Inspyr Therapeutics (Westlake Village, California). However, a stable production of thapsigargin is not established. In vitro regeneration from leaf explants, shoot multiplication and rooting of T. garganica was obtained along with the production of thapsigargins in temporary immersion bioreactors (TIBs). Thapsigargin production was enhanced using reduced nutrient supply in combination with methyl jasmonate elicitation treatments. Shoots grown in vitro were able to produce 0.34% and 2.1% dry weight of thapsigargin and nortrilobolide, respectively, while leaves and stems of wild T. garganica plants contain only between 0.1 and 0.5% of thapsigargin and below detectable levels of nortrilobolide. In addition, a real-time reverse transcription PCR (qRT-PCR) study was performed to study the regulatory role of the biosynthetic genes HMG-CoA reductase (HMGR), farnesyl diphosphate synthase (FPPS), epikunzeaol synthase (TgTPS2) and the cytochrome P450 (TgCYP76AE2) of stem, leaf and callus tissues. Nadi staining showed that the thapsigargins are located in secretory ducts within these tissues. Shoot regeneration, rooting and biomass growth from leaf explants of T. garganica were achieved, together with a high yield in vitro production of thapsigargin in TIBs.


[Study of lamotrigine efficacy on behavior disorders affecting patients with severe mental retardation].
We studied the effect of lamotrigine (LTG) in children/adults with severe mental retardation and behavioral problems. We studied 10 cases with the following conditions: (1) severe or profound mental retardation, (2) various behavioral problems and troubles in daily life, (3) insufficient effects or side effects from antipsychotic drugs, (4) ongoing epileptic seizures or EEG indications of epilepsy, (5) no previous LTG administration, (6) the ability to provide informed consent. We began administering small doses and increased to a maximum dose of LTG in 50 mg/day. We determined the improvement of behavioral problems based on family and patient interviews or our medical examinations. Treatment (still ongoing) has resulted in 7 of the 10 cases showing effects of LTG. Also, 2 of the remaining 3 cases have discontinued medication due to evident changes of mood. Eight cases have showed effects with doses of 10 mg or less per day. We encountered one adult subject who seems to have realized the neuropsychological effect on recognition impairment. We speculated that this patient came to read other people's emotional changes and expected to be either criticized or directed. Small doses of LTG appear to improve behavioral problems in children/adults with severe mental retardation.


The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia: A systematic review and meta-analysis.
Methylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epithelial neoplasia (CIN). We performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted in duplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effects binary regression model were applied to determine pooled effect estimates. 44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamous intra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8-92·2))) vs. low-grade CIN (≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0-74·1))). Pooled difference in mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3% (95%CI:6·5-16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5-8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p < 0·0001). HPV16 L1/L2 genes performed best in predicting CIN2 or worse (pooled sensitivity 77% (95%CI:63-87), specificity 64% (95%CI:55-71), area under the curve (0·73 (95%CI:0·69-0·77)). Higher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use is limited by the need for a multi-genotype and standardised assays. Next-generation multiplex HPV sequencing assays are under development and allow potential for rapid, automated and low-cost methylation testing. NIHR, Genesis Research Trust, Imperial Healthcare Charity, Wellcome Trust NIHR Imperial BRC, European Union's Horizon 2020.


Physical activity prevents bone loss in premenopausal women with rheumatoid arthritis: a cohort study.
The aim of the study was to compare the bone loss and the influence of physical activity between premenopausal women with rheumatoid arthritis (RA) and healthy women. A total of 71 patients with RA and 29 healthy premenopausal women with the criteria of the American College of Rheumatology for RA were followed for 2 years. Of these 85% were Caucasian, aged 38 +/- 6.6 years and with a duration of disease of 88 +/- 50 months and 48 (71.8%) used GC, mean daily dose, 7.3 +/- 3.5 mg. There was a reduction in the T-score of the femoral neck (P = 0.04) and in the Ward region (P = 0.05) in RA. Through logistic regression, it was found that sedentarism was a risk factor for osteopenia in RA, with relative risk of 1.6 (IC = 1.238-1.734). Moderate physical activity reduced the risk of osteopenia by 50%. Sedentarism and low weight are the main factors associated with bone loss. Physical activity reduces bone loss. Early preventive and therapeutic measures must be encouraged.


Doxycycline induces bone repair and changes in Wnt signalling.
Doxycycline (DOX) exhibits anti-inflammatory and MMP inhibitory properties. The objectives of this study were to evaluate the effects of DOX on alveolar bone repair. Controls (CTL) and DOX-treated (10 and 25 mg·kg-1) molars were extracted, and rats were killed 7 or 14 days later. The maxillae were processed and subjected to histological and immunohistochemical assays. Hematoxylin-eosin staining (7th day) revealed inflammation in the CTL group that was partly reversed after DOX treatment. On the 14th day, the CTL group exhibited bone neoformation, conjunctive tissue, re-epithelization and the absence of inflammatory infiltrate. DOX-treated groups exhibited complete re-epithelization, tissue remodelling and almost no inflammation. Picrosirius red staining in the DOX10 group (7th and 14th days) revealed an increased percentage of type I and III collagen fibres compared with the CTL and DOX25 groups. The DOX10 and DOX25 groups exhibited increases in osteoblasts on the 7th and 14th days. However, there were fewer osteoclasts in the DOX10 and DOX25 groups on the 7th and 14th days. Wnt-10b-immunopositive cells increased by 130% and 150% on the 7th and 14th days, respectively, in DOX-treated groups compared with the CTL group. On the 7th day, Dickkopf (Dkk)-1 immunostaining was decreased by 63% and 46% in the DOX10 and DOX25 groups, respectively. On the 14th day, 69% and 42% decreases in immunopositive cells were observed in the DOX10 and DOX25 groups, respectively, compared with the CTL group. By increasing osteoblasts, decreasing osteoclasts, activating Wnt 10b and neutralising Dkk, DOX is a potential candidate for bone repair in periodontal diseases.


Relationship between sun-protection factor and application thickness in high-performance sunscreen: double application of sunscreen is recommended.
High-performance sunscreen protects both healthy consumers and photosensitive patients from strong ultraviolet (UV) exposure. The sun-protection factor (SPF), which indicates the efficacy of UV protection, is determined using a prescribed sunscreen application thickness of 2.0 mg/cm(2). Therefore, users should apply at least 2.0 mg/cm(2) of sunscreen to obtain the level of UV protection expected from a product. In most cases, however, users apply insufficient amounts of sunscreen. To determine the amount of sunscreen applied under specific conditions, and the relationship between application thickness and SPF value in high-performance sunscreen. The amount of applied sunscreen was calculated under practical conditions and conditions that directed a double application. The SPF values of high-performance sunscreen applied at three thicknesses (2.0, 1.0 and 0.5 mg/cm(2)) were determined according to the international SPF testing method. RESULTS. The relationship between SPF value and application thickness correlated in a logarithmic curve. The mean application thickness under practical conditions was approximately 1 mg/cm(2), and directing subjects to use a double application increased the application thickness to nearly 2 mg/cm(2). Encouraging a double application of sunscreen will help users apply products at a thickness sufficient to achieve expected SPF efficacy. We recommend that guidance on double application of sunscreen should be posted in public locations where sunscreen is likely to be in use.


Diabetes-mediated middle cerebral artery remodeling is restored by linagliptin: Interaction with the vascular smooth muscle cell endothelin system.
Endothelin-1 (ET-1) mediates cerebrovascular remodeling in vascular smooth muscle layer of the middle cerebral arteries (MCA) in type-2 diabetic Goto-Kakizaki (GK) rats. While metformin, oral glucose lowering agent, prevent/restores vascular remodeling and reduce systemic and local ET-1 levels whether this effect was specific to metformin remained unknown. Our working hypotheses were 1) linagliptin, a DPP-IV inhibitor, can reverse diabetes-mediated cerebrovascular remodeling and this is associated with decreased ET-1, and 2) linagliptin prevents the high glucose induced increase in ET-1 and ET receptors in brain vascular smooth muscle cells (bVSMCs). Diabetic and non-diabetic GK rats were treated with linagliptin (4weeks). MCAs were fixed in buffered 4% paraformaldehyde and used for morphometry. Human bVSMCs incubated in normal glucose (5.5mM)/high glucose (25mM) conditions were treated with the linagliptin (100nM; 24h). ET-1 secretion and ET receptors were measured in media and cell lysate respectively. Immunostaining was performed for ET-A and ET-B receptor. ET receptors were also measured in cells treated with ET-1 (100nM) and linagliptin. Linagliptin treatment regressed vascular remodeling of MCAs in diabetic animals but had no effect on blood glucose. bVSMCs in normal/high glucose condition did not show any significant difference in ET-1 secretion or ET-A and ET-B receptor expression. ET-1 treatment in high glucose condition significantly increased the ET-A receptors and this effect was inhibited by linagliptin. Linagliptin is effective in reversing established pathological cerebrovascular remodeling associated with diabetes. Attenuation of the ET system could be a pleiotropic effect of linagliptin that provides vascular protection.


Self-care capacity and anticholinergic drug levels in nursing home patients.
The serum anticholinergic levels of 22 demented nursing home patients were related to their cognition and capacity for self-care. The patients with high anticholinergic levels had greater impairment in self-care capacity than patients with low levels.


Early biochemical outcomes following permanent interstitial brachytherapy as monotherapy in 1050 patients with clinical T1-T2 prostate cancer.
Five European centres (France, Finland, Italy, Spain and the UK) have pooled data to generate a large patient series involving 1175 patients treated with prostate brachytherapy. This paper reports preliminary data on PSA outcome up to 4 years. Out of 1175 in the database, 1050 patients with localised prostate cancer who had received transperineal seed implantation as monotherapy between May 1998 and August 2003 were stage T1-T2. A total of 668 (63.6%) patients met the low-risk group definition, 297 (28.3%) as intermediate-risk definition and 66 (6.3%) the high-risk group definition. The majority of patients were Gleason score 6 or less (n=951) and disease stage was T1c in 557 patients. Of the 1050 patients, PSA data up to 4 years were available for 210 patients, while 364 patients with PSA values up to 36 months were evaluable by the Kaplan-Meier method for freedom from biochemical failure. The biochemical progression-free rate at 3 years was estimated to be 91%, with a 93% and 88% rate for low- and intermediate-risk groups, respectively, versus 80% for the high-risk group. PSA kinetics provide encouraging evidence of treatment efficacy. These data on 4-year PSA follow-up on patients treated with prostate brachytherapy reflect those previously reported in the literature. This patient series will be followed to provide long-term outcome in the future.


The role and significance of potential lipid-binding regions in the mitochondrial protein import motor: an in-depth in silico study.
Over the last two decades, an impressive progress has been made in the identification of novel factors in the translocation machineries of the mitochondrial protein import and their possible roles. The role of lipids and possible protein-lipids interactions remains a relatively unexplored territory. Investigating the role of potential lipid-binding regions in the sub-units of the mitochondrial motor might help to shed some more light in our understanding of protein-lipid interactions mechanistically. Bioinformatics results seem to indicate multiple potential lipid-binding regions in each of the sub-units. The subsequent characterization of some of those regions in silico provides insight into the mechanistic functioning of this intriguing and essential part of the protein translocation machinery. Details about the way the regions interact with phospholipids were found by the use of Monte Carlo simulations. For example, Pam18 contains one possible transmembrane region and two tilted surface bound conformations upon interaction with phospholipids. The results demonstrate that the presented bioinformatics approach might be useful in an attempt to expand the knowledge of the possible role of protein-lipid interactions in the mitochondrial protein translocation process.


Antibiotic resistance trends in paediatric uropathogens.
The antimicrobial susceptibility patterns of paediatric uropathogens to six of the most common antibiotics in use for urinary tract infections were determined. The bacterial isolates came from the urine of children presenting as outpatients to participating US hospitals between April 2002 and May 2004. Strains of the six most common uropathogens were included in the analysis. Results were stratified by paediatric age group. In total, 11174 female and 1557 male positive cultures were analysed. The overall resistance rates for females and males, respectively, were as follows: ampicillin 44.3% and 44.6%; sulphamethoxazole/trimethoprim 24.5% and 36.7%; amoxicillin/clavulanic acid 12.4% and 27.5%; cefazolin 10.9% and 27.1%; ciprofloxacin 0.9% and 2.4%; and nitrofurantoin 4.4% and 11.0%. Uropathogen resistance to commonly used antibiotics in the paediatric population was high.


Identification of Long Non-Coding RNA SNHG Family as Promising Prognostic Biomarkers in Acute Myeloid Leukemia.
Small nucleolar RNA host gene (SNHG) family members are newly recognized lncRNAs, which have been revealed to be oncogenes in several cancers. However, little studies investigated the expression and clinical implications of SNHGs in AML. Herein, we systemically determined the prognostic role of the expression of SNHG family members in acute myeloid leukemia (AML). Among the expression of all SNHG family members, we identified that only SNHG7 and SNHG12 expression were found to have prognostic effects on overall survival (OS) and leukemia-free survival (LFS) in AML by Cox regression univariate analysis. Furthermore, Kaplan-Meier analysis showed that SNHG7 higher-expressed cases had markedly longer OS and LFS time than SNHG7 lower-expressed cases, whereas SNHG12 higher-expressed cases had markedly shorter OS and LFS time than SNHG12 lower-expressed cases. Interestingly, SNHG7 and SNHG12 expression were also associated with several prognosis-related clinical/molecular features such as white blood cell counts, FAB/cytogenetic classifications, IDH1 mutation, RUNX1 mutation, and NPM1 mutation. Despite the associations, Cox regression multivariate analysis confirmed the independent prognostic impact of SNHG7 and SNHG12 expression in AML. Notably, we further validated that both SNHG7 and SNHG12 expression was significantly increased in newly diagnosed AML patients. Our findings demonstrated that SNHG7 and SNHG12 expression act as independent prognostic indicators in AML.