Uncharted ground: patterns of professional interaction among complementary/alternative and biomedical practitioners in integrative health care settings.
The development of "integrative health care" (IHC) settings combining various aspects of Western biomedicine and complementary/alternative medicine (CAM) is a relatively recent phenomenon among biomedical and CAM professions. While IHC is recognised internationally and occurs in many different contexts (e.g. clinic or hospital), patterns of interaction between biomedical and CAM practitioners, and the nature of IHC settings, are largely unknown. This paper presents findings from a research study of two newly established IHC settings in Canada. The main research question was: how are biomedical and CAM practitioners integrating or not integrating with each other at the level of professional interaction in IHC settings? Using a case study design, in-depth interviews were conducted with 13 biomedical and eight CAM practitioners during 2002-2003, and ethnographic observation and document analysis was conducted at each site. Drawing from closure theory of the professions, comparative analysis of the sites revealed that biomedical practitioners enact patterns of exclusionary and demarcationary closure, in addition to the use of "esoteric knowledge", by: (a) dominating patient charting, referrals and diagnostic tests; (b) regulating CAM practitioners to a specific "sphere of competence"; (c) appropriating certain CAM techniques from less powerful CAM professions; and (d) using biomedical language as the primary mode of communication. CAM practitioners, in turn, perform usurpationary closure strategies, by: (a) employing their own "esoteric knowledge" in relation to biomedicine and other CAM professions; (b) appropriating biomedical language and terminology; (c) increasing their professional status by working with biomedicine; and (d) referring among CAM practitioners to increase patient flow. The findings suggest that when attempts are made to integrate biomedicine and CAM, dominant biomedical patterns of professional interaction continue to exist. Despite continued patterns of social closure, biomedical and CAM practitioners continue to provide a certain form of integrative care that may be of benefit to patients, albeit not as integrative as current models of integration would prefer.


[Thirty-four years follow-up of a bilateral Mac Kee-Farrar arthroplasty without loosening or osteolysis].
We report the case of a 93-year-old patient with bilateral Mac Kee-Farrar hip arthroplasties implanted 34 years ago. The patient was seen in 2005 for a type B1 periprosthetic fracture on the right prosthesis implanted in 1973. There was no loosening and the fracture was treated by plate fixation. Before the fracture, the Postel-Merle d'Aubigné (PMA) score was 16 on both sides, with a Devane activity score grade 2. At last follow-up, the PMA score was 13 for both hips, with a Devane activity score grade 1. Serum cobalt level was 1.36 microg/L (normal <1 microg/L). This exceptional case is to our knowledge the longest observed with this implant without clinical or radiographic signs of loosening. The serum cobalt level, rarely assayed after more than 30 years, was within the limits accepted for a metal-on-metal hip bilateral arthroplasty. We discuss the causes of failure and success of the Mac Kee-Farrar implant as reported in the literature and remark that long survival of the metal-on-metal bearing can occasionally be observed without signs of wear. Recent works on the metal-on-metal bearing merit attention.


Transanal anastomosis in the treatment of low rectal strictures due to tribal enemas.
Enema administration is common in Black tribal communities. In the urban environment, toxic and corrosive ingredients may be used which can lead to severe complications. The diagnosis and principles of treatment of complicated proctocolitis of enema origin are discussed. The management of 2 patients who developed long stricutres extending low into the rectum is described. After subtotal rectal and sigmoid resection, continuity was successfully restored using a transanal sleeve anastomosis. Subsequent continence was normal in both patients.


Variable regions of antibodies to synthetic polypeptides--I. Characterization of an idiotope expressed on antibodies and T-cell factors.
Spleen cells from a Lewis rat immunized with affinity-purified B10 anti-(T,G)-A-L antibody were fused with the non-secreting murine hybridoma SP2/0. Cell lines secreting monoclonal antibodies specific for mu- and kappa-chains, as well as an idiotope on anti-(T,G)-A-L antibodies, were isolated and characterized. The anti-mu and -kappa antibodies, are true anti-isotypes, reacting with sera from all strains of mice tested. The anti-idiotope antibodies recognize a determinant on antibodies binding a GT-containing epitope. The proportion of anti-GAT antibody bearing the idiotope varies markedly in different murine strains. A 1000-fold higher level of antibody from Igha mice than from Ighb and Ighe mice is required to give an equivalent inhibition of the idiotope-anti-idiotope reaction. Analysis of monoclonal antibodies expressing the idiotope indicates that the affinity of binding between idiotope and anti-idiotope can vary by as much as two orders of magnitude. Immunoadsorbants prepared with anti-idiotope antibody bind suppressor factor secreted by a GAT-specific T-cell hybridoma.


Centrifugal analysis of undiluted packed human erythrocyte lysates. Studies of the association of glyceraldehyde-phosphate dehydrogenase with the membrane fraction.
Concentrated human erythrocyte lysates (greater than 99% initial haematocrit) were subjected to high centrifugal fields. This caused the membrane fraction to separate from the cytoplasmic portion, due to the lower density of the former. Enzyme distribution data indicated that glyceraldehyde-phosphate dehydrogenase was predominantly in the cytoplasmic fraction.


A greater number of somatic pain sites is associated with poor mental health in adolescents: a cross-sectional study.
Identifying indicators of poor mental health during adolescence is a significant public health issue. Previous studies which suggested an association between the number of somatic pains and depression have mainly focused on adults or have employed samples with a narrow age range. To date, results from previous studies have been inconsistent regarding the association between somatic pain and academic impairment. Therefore, the main aims of the present study were to 1) investigate the association between the number of somatic pain sites and poor mental health using a community sample of adolescents aged 12 to 18 years and employing a simple method of assessment, and 2) examine the association between the number of somatic pain sites and perceived academic impairment. Data analysis was conducted using a large cross-sectional survey of adolescents in grades 7 to 12. The one-month prevalence rates for three sites of somatic pain including head, neck and shoulders, and abdomen were examined. Poor mental health was evaluated using the General Health Questionnaire, and perceived academic impairment was measured using a self-report questionnaire. A total of 18,104 adolescents participated in the survey. A greater number of pain sites was associated with poor mental health, and this association was consistent across age and gender. There was no difference in effect on mental health between any of the pain sites. Although there was an association between the number of somatic pain sites and perceived academic impairment, the results suggested that the association was mediated by poor mental health. Simple reporting methods for assessing the number of pain sites may be a feasible indicator of poor mental health in adolescents. Professionals working with adolescents should consider the possibility of poor mental health, especially when students report multiple somatic pains.


Expression of LINC00174 in different cancers: Review of the literature and bioinformatics analyses.
LINC00174 is an example of long intergenic non-coding RNAs with important functions in the development of human cancers. The gene encoding this lincRNA is located on 7q11.21. LINC00174 has been demonstrated to play an oncogenic role in a variety of cancers, including colorectal carcinoma, thymic carcinoma, glioma, glioblastoma, hepatocellular carcinoma, kidney renal clear cell carcinoma, breast cancer and non-functioning pituitary adenoma. In lung cancer, there is an obvious discrepancy between different studies regarding the role of this lincRNA. This lincRNA is also involved in the determination of prognosis of different cancers, particularly colorectal cancer. In the current review, we discuss the role of this lincRNA in human carcinogenesis based on the available data in the literature and bioinformatics tools.


Laparoscopic surgery does not increase the positive peritoneal cytology among women with endometrial carcinoma.
The purpose of our study was to find if uterine manipulation at the time of laparoscopic hysterectomy among women with endometrial carcinoma increases the incidence of malignant cells in the peritoneal washings. We conducted a prospective study including women with clinical stage I endometrioid endometrial carcinoma undergoing laparoscopic surgery between 07/01/2000 and 07/01/2004. Surgery on all patients was conducted by the same surgeon using the same technique and instruments. Two sets of peritoneal washings were obtained, one before and one after the insertion of the Pelosi uterine manipulator. The two sets of washings were blindly reviewed by the same cytopathologist for the presence of malignant cells. Correlation was made between the two sets of washings. Forty-two consecutive women (age 46-90, median: 58) were enrolled in the study. The procedure was converted to laparotomy in 3 (7.6%) patients after obtaining the two sets of washings. The preoperative tumor grades were: G1: 22 (52.4%), G2: 12 (28.6%), and G3: 8 (19.0). The incidence of positive peritoneal washings was 14.3%. All patients underwent laparoscopically assisted vaginal hysterectomy with bilateral salpingo-oophorectomy, 30 patients had bilateral pelvic lymphadenectomy, and 5 patients had bilateral pelvic and para-aortic lymphadenectomy. There was perfect agreement between the two sets of washings in all patients (100%, P < .001). No patients had positive washings after the insertion of the uterine manipulator if the washings were negative before the insertion. The surgical stages were: IA: 14 (33.3%), IB: 12 (28.6%), IC: 7 (16.7%), IIA: 1 (2.4%), IIB: 1 (2.4%), IIIA: 4 (9.5%), IIIB: 1 (2.4%), IIIC: 1 (2.4%), and IV: 1 (2.4%). Twenty-nine patients received no postoperative treatment, 2 received chemotherapy, 3 received Megace, and 9 received radiation therapy. Patients were followed-up for 7-56 months (median: 28). Two patients had tumor recurrence, and one patient died secondary to her disease. Two other patients died secondary to other causes. We conclude that uterine manipulation at the time of laparoscopic hysterectomy does not increase the incidence of positive peritoneal cytology among women with endometrial carcinoma.


Co-localization of corticotropin-releasing hormone with glutamate decarboxylase and calcium-binding proteins in infant rat neocortical interneurons.
Corticotropin releasing hormone (CRH) has been localized to interneurons of the mammalian cerebral cortex, but these neurons have not been fully characterized. The present study determined the extent of co-localization of CRH with glutamate decarboxylase (GAD) and calcium-binding proteins in the infant rat neocortex using immunocytochemistry. CRH-immunoreactive (ir) neurons were classified into two major groups. The first group was larger and consisted of densely CRH-immunostained small bipolar cells, predominantly localized to layers II and III. The second group of CRH-ir cells was lightly labeled and included multipolar neurons mainly found in deep cortical layers. Co-localization studies indicated that the vast majority of CRH-ir neurons, including both bipolar and multipolar types, was co-immunolabeled for GAD-65 and GAD-67. Most multipolar, but only some bipolar, CRH-ir neurons also contained parvalbumin, while CRH-ir neurons rarely contained calbindin or calretinin. These results indicate that virtually all CRH-ir neurons in the rat cerebral cortex are GABAergic. Furthermore, since parvalbumin is expressed by cortical basket and chandelier cells, the co-localization of CRH and parvalbumin suggests that some cortical CRH-ir neurons may belong to these two cell types.


OmpR-dependent and OmpR-independent responses of Escherichia coli to sublethal attack by the neutrophil bactericidal/permeability increasing protein.
Bactericidal/permeability-increasing protein (BPI) of neutrophils is a lipopolysaccharide (LPS)-binding antibacterial protein with specificity for Gram negative bacteria. BPI binding to the bacterial surface rapidly triggers potentially reversible bacterial growth inhibition and alterations of the outer membrane and, later, disruption of the inner membrane and lethal injury. Initial effects include selective OmpR-dependent changes in the synthesis of outer membrane porins (OmpF and OmpC). Because OmpR is a global transcriptional regulator, we have examined its possible role in responses of E. coli to sublethal injury caused by BPI. Early (<15 min) reversible effects of BPI on bacterial colony-forming ability and outer membrane permeability were virtually identical in isogenic wild-type (wt) and ompR- E. coli. Both strains could repair the outer membrane permeability barrier after Mg2+-induced displacement of bound BPI. However, OmpR was essential for the ability of E. coli to tolerate low doses of BPI and escape the progression of sublethal to lethal damage. Scanning electron microscopy revealed that BPI treatment produced greater membrane perturbations in the ompR- strain, apparent even before lethal injury. These findings suggest that the fate of E. coli exposed to BPI depends on both OmpR-independent mechanisms engaged in outer membrane repair and OmpR- dependent processes that modulate porin synthesis and retard progression of injury from the outer to the inner membrane.


Testing the ability for autonomous oral hygiene in hospitalized geriatric patients-clinical validation study.
This study aimed to evaluate if the Timed Test for Money Counting (TTMC) complemented with testing the range of shoulder motion by griping the backside of the neck (NG) predicts the ability of geriatric inpatients to perform effective plaque reduction by autonomously conducted oral hygiene. This clinical validation study involved 74 hospitalized geriatric inpatients, 48 (64.9%) females, aged between 66 and 98 years (mean age 84.1 years). Oral health status was examined. Dental plaque was assessed with the Turesky modified Quigley-Hein Index (TI) on teeth and the Denture Hygiene Index (DHI) on removable dentures. The performance and duration of TTMC and NG were recorded. After autonomous tooth brushing and denture cleaning by the patient, dental plaque was scored again with the TI and DHI. Geriatric assessment data were collected from medical records. Forty-nine (66.2%) geriatric inpatients completed the TTMC&NG successfully. Passing the TTMC&NG was significantly associated with better plaque removal on teeth and dentures by autonomously conducted oral hygiene. The sensitivity of the TTMC&NG for above average plaque reduction was 86.4% on teeth and 77.8% on dentures. The test revealed a negative predictive value of 75.0% to detect below average plaque reduction on teeth and 72.7% on dentures. The TTMC&NG served as a suitable predictor for the ability of geriatric inpatients to perform autonomously effective tooth brushing and denture cleaning. This simple and short test might help the medical staff to identify geriatric inpatients unable to perform effective oral hygiene by themselves.


Effect of dexamethasone upon surfactant phosphatidylcholine and phosphatidylglycerol synthesis in organotypic cultures of type II cells.
Organotypic cultures of pulmonary type II epithelial cells were treated with dexamethasone at concentrations between 10(-10) and 10(-5) M for 48 h followed by a 3 h incubation in 5.6 mM [U-14C]glucose. A surfactant and a residual fraction was isolated from the cultures by discontinuous sucrose gradient centrifugation. Phosphatidylcholine and phosphatidylglycerol were purified from each fraction and analyzed for total content. The specific activity of each phospholipid was measured as an index of the rate of synthesis. Dexamethasone treatment produced a dose-dependent increase in synthesis and content of surfactant phosphatidylcholine, with a maximum response occurring at 10(-6) M dexamethasone. At concentrations of 10(-5) M, dexamethasone ceased to produce a significant stimulation. Dexamethasone produced an increase in surfactant phosphatidylglycerol synthesis only at a concentration of 10(-8) M and higher. There was not a significant effect upon the content or rate of synthesis of phosphatidylcholine or phosphatidylglycerol in the residual fraction at any of the dexamethasone concentrations tested.


Objectively Assessed Cardiorespiratory Fitness and All-Cause Mortality Risk: An Updated Meta-analysis of 37 Cohort Studies Involving 2,258,029 Participants.
To detail the magnitude and specificity of the association between cardiorespiratory fitness (CRF) and all-cause mortality risk. Cohort studies with at least 1 year of follow-up were sought from inception until December 2021 in MEDLINE, Embase, Web of Science, and a manual search of relevant articles. Relative risks (RRs) with 95% CIs were pooled using random-effects models. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. A total of 37 unique studies comprising of 2,258,029 participants with 108,613 all-cause mortality events were eligible. The pooled multivariable-adjusted RR for all-cause mortality comparing the top vs bottom tertiles of CRF levels was 0.55 (95% CI, 0.50 to 0.61). When CRF was expressed in metabolic equivalent task (MET) units, the corresponding pooled RR was 0.56 (95% CI, 0.50 to 0.62). For every 1-MET increase in CRF, the RR for all-cause mortality was 0.89 (95% CI, 0.86 to 0.92). Strength of the association did not differ by publication year, age, sex, follow-up duration, CRF assessment method, or risk of bias. Aggregate analysis of observational cohort studies confirms a strong inverse and independent association between CRF and all-cause mortality risk. The results suggest that guideline bodies should consider the inclusion of CRF in standard risk panels for mortality risk assessment.


Knowledge of COVID-19 and Its Treatment Among Healthcare Worker in Al-Ahsa Region of Saudi Arabia.
To find out how well healthcare workers (HCWs) in Saudi Arabia's eastern region knew about the novel coronavirus illness 2019 (COVID-19) in terms of its symptoms, transmission, and treatment. This is a cross-sectional study conducted in the Saudi Arabian region of Al-Ahsa. Between December 2020 and March 2021, a questionnaire was distributed in the main hospitals in the eastern region: King Fahad Hospital, Prince Saud Bin Jalawi Hospital, Prince Sultan Cardiac Center, and Maternity and Children's Hospital. Participants' knowledge of COVID-19 symptoms, transmission, and treatment was assessed using our developed questionnaire tool. The Student's t-test/ANOVA test was used to compare the mean knowledge scores of different demographic groups. A total of 300 HCWs participated in this study. Our study sample's mean knowledge score was 6.9 (SD = 2.1) out of 13 (53.1%), indicating a marginal degree of understanding. The duration of practice had a significant effect on the participants' knowledge of COVID-19. Senior and non-Saudi HCWs had a higher knowledge score than the rest of the groups (p ≤ 0.05). The majority of the participants were able to identify that COVID-19 is transmitted from human to human through respiratory droplets, populations at higher risk of developing severe complications, populations needing screening for COVID-19, main clinical symptoms of COVID-19, and were following the WHO guidelines for the treatment of COVID-19. According to our findings, HCWs only had marginal knowledge about the symptoms, transmission, and treatment of COVID-19. As our findings represent early investigation at the start of the pandemic, more research is needed to evaluate the degree of information gathered two years after the outbreak began. Furthermore, future research should identify knowledge gaps in the targeted population of HCWs and provide strategies to address them.


[Initial experience with ultrasonic diagnosis of impaired glued connections in dental prosthetics].
The author evaluates the quality of gluing of metal discs by means of Spofacryl on glass, using ultrasound signals. He gives an account of his initial experience with this method which he considers so far suitable only for experimental work.


A multifaceted approach to quality in the MRI-directed biopsy pathway for prostate cancer diagnosis.
• Identify, assure, and measure major sources of variability affecting the MRI-directed biopsy pathway for prostate cancer diagnosis.• Develop strategies to control and minimize variations that impair pathway effectiveness including the performance of main players and team working.• Assure end-to-end quality of the diagnostic chain with robust multidisciplinary team working.


Clinical outcome of teeth treated endodontically with a nonstandardized protocol and root filled with resilon.
The purpose of this study was to evaluate the clinical outcomes of root canal treatment in private practice and filled with Resilon. Immediate postoperative radiographs were compared to follow-up radiographs of at least 1 year in 82 randomly selected primary endodontic cases treated according to a nonstandardized protocol but root-filled with Resilon. The Periapical Index (PAI) and the Clinical Impression of Healing (CIH) quantification procedures were used to determine the status and change in the condition of the teeth. The PAI evaluation revealed that 90% of the teeth that were healthy at the initial reading (PAI, 1or 2) maintained the condition at follow-up evaluation. Of those teeth that were unhealthy (PAI, 3-5) at the initial reading, 73.3% were judged healthy (50%) or improved (23.3) at the last evaluation. In contrast, the proportion of healthy or healing with the CIH evaluation was 89.4%. The findings of this study support the contention that regardless of treatment protocol, healing rates for Resilon-filled teeth in private practice were within the range of success rates for studies with uniform treatment techniques mostly in university settings with gutta-percha root filling.


Highly sensitive spectrofluorimetric method for determination of certain aminoglycosides in pharmaceutical formulations and human plasma.
A simple, reliable, highly sensitive and selective spectrofluorimetric method has been developed for determination of certain aminoglycosides namely amikacin sulfate, tobramycin, neomycin sulfate, gentamicin sulfate, kanamycin sulfate and streptomycin sulfate. The method is based on the formation of a charge transfer complexes between these drugs and safranin in buffer solution of pH 8. The formed complexes were quantitatively extracted with chloroform under the optimized experimental conditions. These complexes showed an excitation maxima at 519-524 nm and emission maxima at 545-570 nm. The calibration plots were constructed over the range of 4-60 pg mL(-1) for amikacin, 4-50 pg mL(-1) for gentamicin, neomycin and kanamycin, 4-40 pg mL(-1) for streptomycin and 5-50 pg mL(-1) for tobramycin. The proposed method was successfully applied to the analysis of the cited drugs in dosage forms. The proposed method was validated according to ICH and USP guidelines with respect to specificity, linearity, accuracy, precision and robustness. The high sensitivity of the proposed method allowed determination of amikacin and gentamicin in spiked and real human plasma.


Communicating with a deafblind person in an emergency.
Deafblind UK is the association of deafblind and dual sensory impaired people in the UK. This paper presents advice on the best way to communicate with people who are disabled in this way, particularly in an emergency.


Mode of transgene expression after fusion to early or late viral genes of a conditionally replicating adenovirus via an optimized internal ribosome entry site in vitro and in vivo.
The expression of therapeutic genes by oncolytic viruses is a promising strategy to improve viral oncolysis, to augment gene transfer compared with a nonreplicating adenoviral vector, or to combine virotherapy and gene therapy. Both the mode of transgene expression and the locale of transgene insertion into the virus genome critically determine the efficacy of this approach. We report here on the properties of oncolytic adenoviruses which contain the luciferase cDNA fused via an optimized internal ribosome entry site (IRES) to the immediate early adenoviral gene E1A (AdDeltaE1AIL), the early gene E2B (AdDeltaE2BIL), or the late fiber gene (AdDeltafiberIL). These viruses showed distinct kinetics of transgene expression and luciferase activity. Early after infection, luciferase activities were lower for these viruses, especially for AdDeltaE2BIL, compared with nonreplicating AdTL, which contained the luciferase gene expressed from the strong CMV promoter. However, 6 days after infection, luciferase activities were approximately four (AdDeltaE1AIL) to six (AdDeltafiberIL) orders of magnitude higher than for AdTL, reflecting virus replication and efficient transgene expression. Similar results were obtained in vivo after intratumoral injection of AdDeltaE2BIL, AdDeltafiberIL, and AdTL. AdDeltafiberIL and the parental virus, Ad5-Delta24, resulted in similar cytotoxicity, but AdDeltaE2BIL and AdDeltaE1AIL were slightly attenuated. Disruption of the expression of neighboring viral genes by insertion of the transgene was minimal for AdDeltaE2BIL and AdDeltafiberIL, but substantial for AdDeltaE1AIL. Our observations suggest that insertion of IRES-transgene cassettes into viral transcription units is an attractive strategy for the development of armed oncolytic adenoviruses with defined kinetics and strength of transgene expression.


In vitro activity of DNF-3 against drug-resistant Mycobacterium tuberculosis.
Due to the emergence of multidrug-resistant and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis, new antituberculosis drugs are urgently required to improve the efficacy of current tuberculosis (TB) treatment. To achieve this goal, ca. 1000 chemical compounds were screened for potential antimycobacterial activity, among which methyl 5-(2-diethylaminoethoxy)-7,12-dioxo-7,12 dihydrodinaphtho[1,2-b;2',3'-d]furan-6-carboxylate (DNF-3) showed strong activity against all of the tested drug-susceptible and -resistant M. tuberculosis strains, with 50% minimum inhibitory concentrations (MIC50 values) of 0.02-0.39 µg/mL both in culture broth and within murine RAW 264.7 macrophage cells. When DNF-3 was used in combination with rifampicin or streptomycin, it exhibited direct synergy against XDR-TB and an additive effect against M. tuberculosis H37Rv. DNF-3 displayed a long post-antibiotic effect (PAE) that was comparable with rifampicin but was superior to isoniazid, streptomycin and ethambutol. Importantly, DNF-3 showed no cytotoxicity to any cell line tested, with a selectivity index (SI) of >32. DNF-3 was also active against 27 nontuberculous mycobacteria (NTM) strains, Staphylococcus spp. and Streptococcus spp. Taken together, these results indicate that DNF-3 is a promising new candidate drug for treating TB. Further studies are warranted to establish the in vivo effect and therapeutic potential of DNF-3.


Retracted: Analysis of Intervention Effect and Satisfaction of Holistic Nursing after Oral Tumor Resection.
[This retracts the article DOI: 10.1155/2022/3788605.].


Changing p53 mutations with the evolution of chronic myeloid leukaemia from the chronic phase to blast crisis.
The frequent involvement of chromosome 17p abnormalities in the progression of chronic myeloid leukaemia (CML) led us to investigate the involvement of the p53 tumour suppressor gene located on chromosome 17p. We analysed 31 samples from four patients sequentially, and 16 patients in blast crisis only, using single stranded conformational polymorphism (SSCP) analysis of exons 5-8, followed by cloning and sequencing. The sequential samples ranged from diagnosis through to late disease. We found that 15% of our blast crisis samples had p53 abnormalities. In our sequential studies we found two of the four patients analysed in more detail had p53 mutations in the late chronic phase of disease (11 and 5 months prior to blast crisis becoming apparent). These chronic phase mutations differed from the p53 abnormalities found in the blast crisis samples from these patients. One patient also had the same chronic phase mutation at post bone marrow transplant relapse. Our results suggest that, in some cases, sequential investigations through CML disease progression of p53 mutations and other oncogenes/proto-oncogenes may provide early indications of the routes of disease progression to blast crisis.


Renal accumulation of amikacin, tobramycin and gentamycin in the rat.
Free and total concentrations of amikacin, tobramycin and gentamycin were measured separately in the rat kidney after equal weight by weight doses. The accumulation of aminoglycosides followed the order amikacin less than tobramycin less than gentamycin. The ratio between free and total aminoglycosides was similar (about 0.6) in all 3 aminoglycosides and independent on the length of administration.


Evaluation of the Humphrey A.D.E. breathing system.
A new breathing circuit (the Humphrey A.D.E., double lever model) was evaluated in adults to determine (1) the fresh gas flow (FGF) needed to achieve normocapnia during controlled ventilation and to just induce rebreathing during spontaneous ventilation, (2) end-expired CO2 (PECO2) at those FGF values, (3) the standard deviation of FGF requirements for controlled and spontaneous breathing (reliability of recommended FGF settings) and (4) the magnitude of change in PECO2 produced by varying FGF from the recommended values (sensitivity of the system). The FGFs that provided normocapnia with controlled ventilation and just induced rebreathing with spontaneous ventilation were 67 +/- 10 and 52 +/- 7 ml . kg-1 . min-1 (mean +/- SD), respectively. PECO2 values were 36.0 +/- 0.3 and 41.6 +/- 3.9 mmHg respectively. During controlled ventilation low reliability was offset by low sensitivity so that PECO2 changed little when FGF was raised or lowered from recommended values (0.2 mmHg/ml . kg-1 . min-1). In contrast, during spontaneous ventilation low reliability was additive with high sensitivity when using FGFs lower than the mean value that just induced rebreathing. A threshold was reached where lowering FGF from recommended values caused large changes in PECO2 (1.1 mmHg/ml . kg-1 . min-1). It is concluded that the FGF recommended by Humphrey for controlled ventilation is satisfactory. However, the FGF recommended by Humphrey for spontaneous ventilation may result in hypercapnia in some patients. This can be prevented either by using a higher FGF of 66 ml . kg-1 . min-1 routinely in all patients or by using lower flows with CO2 monitoring.


RGS14 at the interface of hippocampal signaling and synaptic plasticity.
Learning and memory are encoded within the brain as biochemical and physical changes at synapses that alter synaptic transmission, a process known as synaptic plasticity. Although much is known about factors that positively regulate synaptic plasticity, very little is known about factors that negatively regulate this process. Recently, the signaling protein RGS14 (Regulator of G protein Signaling 14) was identified as a natural suppressor of hippocampal-based learning and memory as well as synaptic plasticity within CA2 hippocampal neurons. RGS14 is a multifunctional scaffolding protein that integrates unconventional G protein and mitogen-activated protein (MAP) kinase signaling pathways that are themselves key regulators of synaptic plasticity, learning, and memory. Here, we highlight the known roles for RGS14 in brain physiology and unconventional G protein signaling pathways, and propose molecular models to describe how RGS14 may integrate these diverse signaling pathways to modulate synaptic plasticity in CA2 hippocampal neurons.


Novel roles of specific isoforms of protein kinase C in activation of the c-fos serum response element.
Protein kinase C (PKC) is a multigene family of enzymes consisting of at least 11 isoforms. It has been implicated in the induction of c-fos and other immediate response genes by various mitogens. The serum response element (SRE) in the c-fos promoter is necessary and sufficient for induction of transcription of c-fos by serum, growth factors, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). It forms a complex with the ternary complex factor (TCF) and with a dimer of the serum response factor (SRF). TCF is the target of several signal transduction pathways and SRF is the target of the rhoA pathway. In this study we generated dominant-negative and constitutively active mutants of PKC-alpha, PKC-delta, PKC-epsilon, and PKC-zeta to determine the roles of individual isoforms of PKC in activation of the SRE. Transient-transfection assays with NIH 3T3 cells, using an SRE-driven luciferase reporter plasmid, indicated that PKC-alpha and PKC-epsilon, but not PKC-delta or PKC-zeta, mediate SRE activation. TPA-induced activation of the SRE was partially inhibited by dominant negative c-Raf, ERK1, or ERK2, and constitutively active mutants of PKC-alpha and PKC-epsilon activated the transactivation domain of Elk-1. TPA-induced activation of the SRE was also partially inhibited by a dominant-negative MEKK1. Furthermore, TPA treatment of serum-starved NIH 3T3 cells led to phosphorylation of SEK1, and constitutively active mutants of PKC-alpha and PKC-epsilon activated the transactivation domain of c-Jun, a major substrate of JNK. Constitutively active mutants of PKC-alpha and PKC-epsilon could also induce a mutant c-fos promoter which lacks the TCF binding site, and they also induce transactivation activity of the SRF. Furthermore, rhoA-mediated SRE activation was blocked by dominant negative mutants of PKC-alpha or PKC-epsilon. Taken together, these findings indicate that PKC-alpha and PKC-epsilon can enhance the activities of at least three signaling pathways that converge on the SRE: c-Raf-MEK1-ERK-TCF, MEKK1-SEK1-JNK-TCF, and rhoA-SRF. Thus, specific isoforms of PKC may play a role in integrating networks of signal transduction pathways that control gene expression.


Outcomes with and without outpatient SARS-CoV-2 treatment for patients with COVID-19 and systemic autoimmune rheumatic diseases: A retrospective cohort study.
To investigate temporal trends, severe outcomes, and rebound among systemic autoimmune rheumatic disease (SARD) patients according to outpatient SARS-CoV-2 treatment. We performed a retrospective cohort study investigating outpatient SARS-CoV-2 treatments among SARD patients at Mass General Brigham (23/Jan/2022-30/May/2022). We identified SARS-CoV-2 infection by positive PCR or antigen test (index date=first positive test) and SARDs using diagnosis codes and immunomodulator prescription. Outpatient treatments were confirmed by medical record review. The primary outcome was hospitalization or death within 30 days following the index date. COVID-19 rebound was defined as documentation of negative then newly-positive SARS-CoV-2 tests. The association of any vs. no outpatient treatment with hospitalization/death was assessed using multivariable logistic regression. We analyzed 704 SARD patients with COVID-19 (mean age 58.4 years, 76% female, 49% with rheumatoid arthritis). Treatment as outpatient increased over calendar time (p<0.001). A total of 426(61%) received outpatient treatment: 307(44%) with nirmatrelvir/ritonavir, 105(15%) with monoclonal antibodies, 5(0.7%) with molnupiravir, 3(0.4%) with outpatient remdesivir, and 6(0.9%) with combinations. There were 9/426 (2.1%) hospitalizations/deaths among those treated as outpatient compared to 49/278 (17.6%) among those with no outpatient treatment (adjusted odds ratio [aOR] 0.12, 0.05 to 0.25). 25/318 (8%) of patients who received oral outpatient treatment had documented COVID-19 rebound. Outpatient treatment was strongly associated with lower odds of severe COVID-19 compared to no outpatient treatment. At least 8% of SARD patients experienced COVID-19 rebound. These findings highlight the importance of outpatient COVID-19 treatment for SARD patients and the need for further research on rebound. Previous studies suggest that monoclonal antibodies are an effective outpatient treatment option for patients at high-risk of severe COVID-19, including those with systemic autoimmune rheumatic diseases (SARDs).Nirmatrelvir/ritonavir and molnupiravir are recently-authorized effective oral outpatient SARS-CoV-2 treatment options, but clinical trials were performed among the general population, mostly among unvaccinated and prior to Omicron viral variants.Oral outpatient SARS-CoV-2 treatments may result in COVID-19 rebound, characterized by newly-positive COVID-19 testing and recurrent symptoms, but no studies have investigated rebound prevalence among SARD patients. This is one of the first studies investigating outpatient SARS-CoV-2 treatments among SARD patients that includes oral options and quantifies the prevalence of COVID-19 rebound.Outpatient treatment was associated with 88% reduced odds of severe COVID-19 compared to no treatment.At least 8% of SARDs receiving oral outpatient treatment experienced COVID-19 rebound. These results should encourage clinicians to prescribe and SARD patients to seek prompt outpatient COVID-19 treatment.This research provides an early estimate of the prevalence of COVID-19 rebound after oral outpatient treatment to quantify this risk to clinicians and SARD patients and encourage future research.


Multi-year survival of sugarbeet root maggot (Tetanops myopaeformis) larvae in cold storage.
To test the hypothesis that long-term survival of sugarbeet root maggot in storage is facilitated by larvae undergoing prolonged diapause, respiration and gene expression patterns of field-collected diapausing larvae were compared with those of 1-, 2-, and 5-year laboratory-stored larvae. Additional assessments were made on post-storage survival, emergence, and reproductive fitness of stored larvae. Respirometry, carried out at 5 and 20 degrees C revealed no differences among respiration rates of initially diapausing and long-term stored larvae. A 15 degrees increase in temperature elevated respiration in both diapausing and stored larvae, with levels of CO2 release ranging between 8- and 14-fold higher at 20 degrees C than at 5 degrees C. Similarly, 6-10-fold increases in O2 consumption levels were observed at the higher temperature. A transcript with sequence similarity to the fat body protein 2 (Fbp2) gene was highly expressed in diapausing larvae, and trace levels were expressed in some samples of 1-year stored larvae. However, no expression was detected in 2- and 5-year stored larvae. Survival and emergence studies of stored larvae revealed mixed populations of diapausing (i.e., the 5-17% of larvae that did not pupate) and post-diapausing (62-84% of larvae pupated) insects, with a high incidence of pupation (62%) and emergence (47%), even after 4 years in cold storage. Therefore, extended survival of Tetanops myopaeformis larvae in long-term cold storage is facilitated by two mechanisms, with a majority of larvae in post-diapause quiescence and a smaller fraction in a state of prolonged diapause.


Factors Leading to Self-Removal from the Bariatric Surgery Program After Attending the Orientation Session.
Bariatric surgery orientation sessions are often the first point of contact and a recommended component of pre-bariatric surgery assessment. Self-removal rates after bariatric program orientation are as high as 25 % despite the proven efficacy of this procedure. The objective of this study was to identify factors contributing to patient self-removal after orientation using a mixed method approach. Patients who attended the Toronto Western Hospital Bariatric Surgery Program orientation between 2012 and 2013 and then self-removed from the program (N = 216) were included in the study. Subjects were interviewed via telephone using a semi-structured interview guide, generating both quantitative and qualitative data. Factors leading to discontinuation were rated on a five-point Likert scale. Qualitative data was analyzed using constant comparative methodology. The response rate was 59 % with a 40.7 % completion rate (N = 88). Concerns about potential surgical risks and complications and the ability to adapt to changes in eating and drinking post-operatively were identified as the top two factors for patients' self-removal from the program. Thematic analysis uncovered 11 major themes related to patient self-removal. Unexpected themes include perceived personal suitability for the surgery, family impact of surgery, miscommunication with the family physician, and fears related to the orientation information. This is one of the first studies examining barriers to bariatric surgery in the pre-operative setting and offers new insights into the reasons patients self-remove from bariatric surgery programs. This study may inform bariatric orientation program changes resulting in improved access to this effective surgical intervention.


Smad protein mediated transforming growth factor beta1 induction of apoptosis in the MDPC-23 odontoblast-like cell line.
The function of apoptosis and its regulation in odontoblasts remain unclear. In this study, we characterize the possible role of transforming growth factor (TGF)-beta 1 in the induction of apoptosis and the molecular mechanisms that mediate TGF-beta1-induced apoptosis in odontoblasts. Annexin V/propidium iodide staining, cell Death Detection ELISA and DNA ladder were used to examine the effect of TGF-beta1 on apoptosis in a mouse odontoblast-like cell line, MDPC-23. Stable cell clones expressing Smad2 or Smad3 dominant negative mutants, or wild-type Smad7 were constructed to investigate the role of Smad proteins in the mediation of apoptosis by TGF-beta1 in MDPC-23 cells. The TGF-beta1-induced transcriptional activity in stable cell clones expressing Smad proteins was analyzed by a transient transfected TGF-beta-responsive reporter gene, p3TP-Lux. TGF-beta1 can induce apoptotic cell death in MDPC-23 cells in a dose-dependent manner. Transfection of dominant negative mutant forms of Smad2 or Smad3 blocked TGF-beta1-induced apoptosis; moreover, the Smad3 mutant was more efficient than the Smad2 mutant. Transfection of Smad7, an inhibitory Smad, also significantly inhibited TGF-beta1-induced apoptosis of these cells. Over-expression of Smad3 dominant negative mutant or Smad7 significantly inhibited TGF-beta1-induced transcriptional activity. These results suggest that Smad proteins are involved in TGF-beta1-induced apoptosis of odontoblast cells.


Nucleotide sequence, structural organization and host range of pRS4, a small cryptic Pediococcus pentosaceus plasmid that contains two cassettes commonly found in other lactic acid bacteria.
The complete nucleotide sequence of the cryptic plasmid pRS4 (3550 bp) from Pediococcus pentosaceus RS4 was determined. Sequence analysis revealed the presence of three open reading frames (ORFs). The putative protein coded by ORF 1 showed 93% identity with the mobilization protein of Lactobacillus casei plasmid pLC88 and 94% identity with a sequenced fragment of the mobilization protein of P. damnosus plasmid pF8801, suggesting a common origin for these three mobilization proteins. The putative protein coded by ORF 2 showed 92% identity with the replication protein of L. plantarum plasmid pWCFS101, a plasmid that replicates via the rolling circle (RC) mechanism, suggesting a similar replication mechanism for pRS4. Supporting this hypothesis, a putative double strand origin (dso) and a region with palindromic sequences that could function as single strand origin (sso), were detected in pRS4. A function could not be assigned to ORF 3. Since ORF 1 exhibits high identity with L. casei plasmid pLC88 but lower identity (58%) with other Lactobacillus plasmids, and ORF 2 exhibits high identity with the L. plantarum plasmid pWCFS101 but lower identity (55-58%) with other Lactobacillus plasmids (including pLC88), two independent cassettes, from different sources, seem to be involved in the structure of pRS4. Plasmids derived from pRS4 containing the chloramphenicol resistance gene were successfully electrotransformed in L. plantarum, L. casei, P. pentosaceus, and Pediococcus acidilactici, suggesting that pRS4 could be used as a cloning vector for lactic acid bacteria. To our knowledge pRS4 is the first RC-replicating plasmid of P. pentosaceus that has been completely sequenced and used as cloning vector.


Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene.
More and more H5N1 subtype avian influenza viruses possessing a 15-nucleotide (15-nt) deletion in the viral nonstructural protein (NS) gene from position 263 to 277 have emerged since 2000. In order to investigate the biological significance of this deletion, two pairs of H5N1 reassortants designated as rWSN-SD versus rWSN-mSD and rWSN-YZ versus rWSN-mYZ were generated by reverse genetics technique. These recombinant viruses shared the same inner genes of PB1, PB2, PA, NP, and M from strain A/WSN/33(H1N1) and outer genes of HA and NA from strain A/Duck/Shandong/093/2004 (H5N1) (A/D/SD/04), whereas they bore different NS gene. Recombinant rWSN-SD carried the full sequence NS gene from A/D/SD/04 in the natural state without deletion, whereas rWSN-mSD carried the same NS gene, but with an artificial 15-nt deletion from position 263 to 277. On the other hand, rWSN-YZ contained the NS gene in the natural state with a deletion from A/Duck/Yangzhou/232/2004 (H5N1) (A/D/YZ/04), while rWSN-mYZ bore the same NS gene but with an artificial insertion of 15-nt in site 263-277. All the four reassortants grew well in embryonated chicken eggs with similar mean death time (MDT) and viral titer of EID50 or HA. However, the virulence of these reassortant viruses in chickens and mice was different. Reassortant viruses with deletion in their NS gene (rWSN-mSD and rWSN-YZ) had much higher intraveneous pathogenicity index (IVPI) in chickens and lower MLD50 in mice than their counterparts without the deletion (rWSN-SD and rWSN-mYZ). Furthermore, rWSN-mSD and rWSN-YZ caused significantly more deaths in infected chickens and higher virus titers in tissues of inoculated mice than did rWSN-SD and rWSN-mYZ respectively. Sequence analysis also showed that H5N1 viruses carrying the 15-nt deletion in the NS gene invariably had the D92E shift in their NS1 protein. The results indicated that the 15-nucleotide deletion of NS gene from site 263 to 277 associated with D92E shift in NS1 protein contributes to the virulence increase of H5N1 viruses in chickens and mice.


Improved outcome with novel device for low-pressure PTCA in de novo and in-stent lesions.
Complex lesion morphology requiring the use of high pressure to effect lumen expansion and in-stent restenosis (ISR) remain two indications that challenge conventional PTCA balloons. We report on a new PTCA device that is designed to provide precise, low-pressure dilatation of both de novo and in-stent lesions. The FX miniRAIL catheter (FX) has an integral wire positioned external to a dilating balloon and a short, 12-mm guidewire lumen distal to the balloon. The balloon inflates against the guidewire and the external wire to prevent slippage and to introduce high focal longitudinal stresses at low inflation pressures. In this initial study, the FX was used in 37 lesions (25 de novo, 12 in-stent; vessel reference diameter=2.73+/-0.49 mm) in 30 patients. A stepwise inflation protocol and QCA were used to determine the balloon pressure at which the stenosis was resolved (stenosis resolution pressure, SRP). All lesions (100%) were easily reached, crossed and dilated without complication. The SRP was 4.5+/-2.9 atm, and no balloon slippage was observed. Residual stenosis after FX was 26.39+/-13.29%. Minor dissections (Types A and B) were observed in eight lesions (21.6%). Target lesion revascularization (TLR) and target vessel revascularization (TVR) at follow-up (8.1+/-1.5 months) were 8.3% and 12.5%, respectively. The design of the FX is versatile and appears to provide for a safe, effective and improved low-pressure PTCA technique in de novo and in-stent lesions.


Quantifying the effect of an endo-vaginal probe on position of the pelvic floor viscera and muscles.
Endovaginal ultrasound has long been hypothesized to have a significant effect on locations of what it visualizes. However, little work has directly quantified its effect. This study aimed to quantify it. This cross-sectional study consisted of 20 healthy asymptomatic volunteers who underwent both endovaginal ultrasound and MRI. The urethra, vagina, rectum, pelvic floor, and pubic bone were segmented in both ultrasound and MRI using 3DSlicer. Then, using 3DSlicer's transform tool the volumes were rigidly aligned based on the posterior curvature of the pubic bone. The organs were then split into thirds along their long axis to compare their distal, middle, and proximal sections. Using Houdini, we compared the location of the centroid of each of the urethra, vagina, and rectum and the surface-to-surface difference of the urethra and rectum. The anterior curvature of the pelvic floor was also compared. Normality of all variables was assessed by Shapiro-Wilk test. The largest amount of surface-to-surface distance was observed in the proximal region for the urethra and rectum. Across all three organs, the majority of the deviation was in the anterior direction for geometries obtained from ultrasound versus those from MRI. For each subject, the trace defining the midline of the levator plate was more anterior for ultrasound compared to MRI. While it has often been assumed that placing a probe in the vagina probably distorts the anatomy, this study quantified the distortion and displacement of the pelvic viscera. This allows for better interpretation of clinical and research findings based on this modality.


Synergistic agents for tumor-specific therapy mediated by focused ultrasound treatment.
This minireview highlights the recent advances in the therapeutic agents that aim to provide synergistic enhancements of focused ultrasound treatment of tumors. Even though focused ultrasound therapy itself can bring therapeutic effects in cancers, many biochemical agents have been reported in the literature to enhance the treatment efficacy significantly. Until now, many mechanisms have been researched to advance the therapy, such as sonodynamic-plus-chemo-therapy, microbubble-aided therapy, localized release or delivery of nanomaterials, and multimodal image-guided therapy. Here, the novel materials adopted in each mechanism are briefly reviewed to provide a trend in the field and encourage future research towards the successful deployment of focused ultrasound therapy in real clinical environments.


Personality and oral health-related quality of life. Results from an online survey.
To investigate the association between personality factors and oral health-related quality of life. Data were taken from an online survey (representative for the general adult population in Germany in terms of region, sex and age group; n = 3,075) performed in late summer 2021. The well-established Oral Health Impact Profile (OHIP-G5) was used to measure oral health-related quality of life. Moreover, the established 10 Item Big Five Inventory (BFI-10) was used to quantify personality factors (in terms of agreeableness, conscientiousness, extraversion, neuroticism, and openness to experience). Sex, age, family status, educational level, smoking status, alcohol consumption, sports activities, presence of chronic diseases and self-rated health were adjusted for in multiple linear regression analysis. Pearson correlations between oral health-related quality of life and personality factors ranged from r =- 0.17 (conscientiousness) to r = 0.17 (neuroticism). Regressions revealed that low oral health-related quality of life is associated with higher neuroticism (β = 0.39, p < 0.001) and lower conscientiousness (β=-0.51, p < 0.001). This study revealed an association between personality factors (higher neuroticism and lower conscientiousness) and low oral health-related quality of life. Before dental treatment, it may be helpful to measure personality traits of patients in order to predict the expectations of patients, as well as their responses to intended treatments. This may support the identification of the most appropriate method of treatment.


Descriptive parameter evaluation in mammalian cell culture.
Several methods exist for assessing population growth and protein productivity in mammalian cell culture. These methods were critically examined here, based on experiments with two hybridoma cell lines. It is shown that mammalian cell culture parameters must be evaluated on the same basis. In batch culture mode most data is obtained on a cumulative basis (protein product titre, substrate concentration, metabolic byproduct concentration). A simple numerical integration technique can be employed to convert cell concentration data to a cumulative basis (cell-hours). The hybridoma lines used in this study included a nutritionally non-fastidious line producing low levels of MAb and a nutritionally fastidious hybridoma with high productivity. In both cases the cell-hour approach was the most appropriate means of expressing the relationship between protein productivity and cell population dynamics. The cell-hour approach could be used as the basis for all metabolic population parameter evaluations. This method has the potential to be used successfully for both prediction and optimization purposes.


Phacoemulsification versus peripheral iridotomy in the management of chronic primary angle closure: long-term follow-up.
Primary angle closure occurs as a result of crowded anterior segment anatomy, causing appositional contact between the peripheral iris and trabecular meshwork, thereby obstructing aqueous outflow. Several studies highlight the role of the crystalline lens in its pathogenesis. The objective of this work is to compare the long-term efficacy of phacoemulsification versus laser peripheral iridotomy (LPI) in the management of chronic primary angle closure (CPAC). Prospective case-control study with 30 eyes of 30 patients randomly divided in two groups: 15 eyes in the LPI group and 15 eyes in the IOL group. Patients in the LPI group underwent LPI using argon and Nd:YAG laser. Patients in the IOL group underwent phacoemulsification with posterior chamber intraocular lens (IOL) implantation. Examinations before and after the procedure included gonioscopy, Goldmann applanation tonometry, and anterior chamber evaluation using the Pentacam rotating Scheimpflug camera. The mean follow-up time was 31.13 ± 4.97 months. There was a statistically significant reduction in the intraocular pressure (IOP) and number of anti-glaucoma medications (p < 0.01) only in the IOL group. Anterior chamber depth, angle, and volume were all higher in the IOL group (p < 0.01) at the end of the follow-up period. Phacoemulsification with posterior chamber IOL implantation results in a higher anterior chamber depth, angle, and volume, when compared to LPI. Consequently, phacoemulsification has greater efficacy in lowering IOP and preventing its long-term increase in patients with CPAC and cataract.


Rv2131c from Mycobacterium tuberculosis is a CysQ 3'-phosphoadenosine-5'-phosphatase.
Mycobacterium tuberculosis ( Mtb) produces a number of sulfur-containing metabolites that contribute to its pathogenesis and ability to survive in the host. These metabolites are products of the sulfate assimilation pathway. CysQ, a 3'-phosphoadenosine-5'-phosphatase, is considered an important regulator of this pathway in plants, yeast, and other bacteria. By controlling the pools of 3'-phosphoadenosine 5'-phosphate (PAP) and 3'-phosphoadenosine 5'-phosphosulfate (PAPS), CysQ has the potential to modulate flux in the biosynthesis of essential sulfur-containing metabolites. Bioinformatic analysis of the Mtb genome suggests the presence of a CysQ homologue encoded by the gene Rv2131c. However, a recent biochemical study assigned the protein's function as a class IV fructose-1,6-bisphosphatase. In the present study, we expressed Rv2131c heterologously and found that the protein dephosphorylates PAP in a magnesium-dependent manner, with optimal activity observed between pH 8.5 and pH 9.5 using 0.5 mM MgCl 2. A sensitive electrospray ionization mass spectrometry-based assay was used to extract the kinetic parameters for PAP, revealing a K m (8.1 +/- 3.1 microM) and k cat (5.4 +/- 1.1 s (-1)) comparable to those reported for other CysQ enzymes. The second-order rate constant for PAP was determined to be over 3 orders of magnitude greater than those determined for myo-inositol 1-phosphate (IMP) and fructose 1,6-bisphosphate (FBP), previously considered to be the primary substrates of this enzyme. Moreover, the ability of the Rv2131c-encoded enzyme to dephosphorylate PAP and PAPS in vivo was confirmed by functional complementation of an Escherichia coli Delta cysQ mutant. Taken together, these studies indicate that Rv2131c encodes a CysQ enzyme that may play a role in mycobacterial sulfur metabolism.


Polar constituents from the aerial parts of Origanum vulgare L. Ssp. hirtum growing wild in Greece.
From the polar extracts of Origanum vulgare L. ssp. hirtum 19 compounds have been isolated. The structures and relative stereochemistry have been elucidated by spectroscopic analysis and determined as apigenin, luteolin, chrysoeriol, diosmetin, quercetin, eriodictyol, cosmoside, vicenin-2, caffeic acid, p-menth-3-ene-1,2-diol 1-O-beta-glucopyranoside, thymoquinol 2-O-beta-glucopyranoside, thymoquinol 5-O-beta-glucopyranoside, thymoquinol 2,5-O-beta-diglucopyranoside, 12-hydroxyjasmonic acid, 12-hydroxyjasmonic acid 12-O-beta-glucopyranoside, lithospermic acid B, rosmarinic acid, 10-epi-lithospermic acid, and epi-lithospermic acid B. The three latter products display unusual stereochemistry of the 3,4-hydroxyphenyllactic acid unit(s), which to the authors' best knowledge has never been reported before in similar compounds. Moreover, lithospermic acid B (and its stereoisomers), p-menth-3-ene-1,2-diol 1-O-beta-glucopyranoside, 12-hydroxyjasmonic acid, and 12-hydroxyjasmonic acid 12-O-beta-glucopyranoside were isolated for the first time from Origanum species.


The clearance of cadmium aerosols after inhalation exposure.
CdO and CdCl2 aerosols were inhaled by two groups of rats and their subsequent clearance behaviour was studied. The half-life of the long term lung clearance rates was identical for both compounds, namely 67 days. For CdO, an initial faster clearance was observed, whereas the initial clearance of CdCl2 did not differ from its long term clearance rate, resulting in a relatively higher Cd burden of the lung in the CdCl2 study. Cd liver and kidney concentrations were also higher in the CdCl2 study, originating from a high resorption rate duringthe time of the exposure.


A distribution model of the responses to each depressive symptom item in a general population: a cross-sectional study.
Some researchers have reported that distribution of total depressive symptom scores in the general population may follow an exponential pattern except at the lowest end of the scores. To understand the mechanism responsible for this phenomenon, we investigated the mathematical patterns of the individual distributions for each item of a depressive symptom scale. We analysed data from 32,022 participants in the general population who participated in the Active Survey of Health and Welfare, Japan. Depressive symptoms were assessed using the Japanese version of Center for Epidemiologic Studies Depression Scale (CES-D). CES-D has 20 items, each of which is scored in 4 grades: 'Rarely', 'Some', 'Much' and 'Most of the time'. The individual distributions of 16 negative items belonging to the depressive mood, somatic symptoms and retarded activities, and interpersonal relations categories, followed a common mathematical pattern, which displayed different distributions with a boundary at 'Some'. The distributions for the 16 items between 'Rarely' and 'Some' appeared to cross at a single point. On the other hand, the distributions of the 16 items between 'Some' and 'Most' followed a linear pattern when plotted using a log-normal scale. The remaining 4 items in the positive affect subscale showed non-specific patterns. The common mathematical pattern of the 16 negative item distributions may contribute to the exponential pattern of the distribution of total depressive symptom scores except at the lowest end of the scores.


Health effects of repeated victimization among school-aged adolescents in six major cities in China.
Child victimization is a public health concern in China. Existing studies documented associations between victimization and negative health effects, while cumulative health effects of repeated victimization have attracted relatively little attention from scholars. To examine the health effects of various types of repeated victimization by using a large representative sample of school children in six major cities in China. This study used data from a large representative sample of 18,452 Chinese adolescents aged 15-17 from six cities, Tianjin, Shenzhen, Shanghai, Xi'an, Wuhan, and Hong Kong. We carried out a two-stage data analysis in this study, including descriptive statistics to describe the prevalence of repeated victimization, and multiple analysis of variance (MANOVA) to examine the health consequences of repeated victimization. 27.54% of respondents experienced one-time victimization, and 44.26% suffered repeated victimizations, and those adolescents with repeated victimization reported significantly higher levels of depression and lower levels of self-esteem and overall health when compared to those with one-time victimization and those without victimization experience. Experiences of repeated victimization can have much stronger associations with negative health outcomes when compared to experiences of one-time victimization. Promoting awareness of both the severity and repetition of victimization and designing integrative screening tool could be meaningful strategies to address the issue of child victimization in China.


Cold-induced fluid extravasation during cardiopulmonary bypass in piglets can be counteracted by use of iso-oncotic prime.
Hypothermic cardiopulmonary bypass is associated with increased fluid extravasation. This study aimed to compare whether iso-oncotic priming solutions, in contrast to crystalloids, could reduce the cold-induced fluid extravasation during cardiopulmonary bypass in piglets. Three groups were studied: the control group (CT group; n = 10), the albumin group (Alb group; n = 7), and the hydroxyethyl starch group (HES group; n = 7). Prime (1000 mL) and supplemental fluid were acetated Ringer solution, 4% albumin, and 6% hydroxyethyl starch, respectively. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (cooling to 28 degrees C within 15 minutes) was initiated and continued to 90 minutes. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit levels, and tissue water content were recorded, and protein masses and fluid extravasation rates were calculated. Colloid osmotic pressure in plasma decreased immediately after the start of cardiopulmonary bypass in the CT group but remained stable in the Alb and HES groups. Colloid osmotic pressure in interstitial fluid tended to decrease in the CT group and remained unchanged in the Alb group, whereas a slight increase was observed in the HES group. Immediately after the start of cooling, fluid extravasation rates increased from 0.15 +/- 0.10 to 0.64 +/- 0.12 mL . kg -1 . min -1 in the CT group, whereas no such increase was observed in the Alb and HES groups. The changes in fluid extravasation rates were reflected by corresponding changes in tissue water content. The use of albumin or hydroxyethyl starch as prime to preserve the colloid osmotic pressure during cardiopulmonary bypass causes a reduction in the cold-induced fluid extravasation compared with that seen with crystalloids. Albumin seems more effective than hydroxyethyl starch to limit cold-induced fluid shifts during cardiopulmonary bypass.


Natural contraception.
This article discusses some complementary and alternative medicine options for contraception, including natural family planning and plant-derived hormonal contraception. Primary care providers are crucial resources for advice and recommendations about these options. The discussion will include medical evidence to support or refute these methods, potential dangers of these interventions, and additional resources for those who want to learn more.


Overcoming gendered and professional hierarchies in order to facilitate escalation of care in emergency situations: the role of standardised communication protocols.
It has been suggested that as many as 23,000 in-hospital cardiac arrests in the UK could be prevented with earlier detection and intervention (Hodgetts et al., 2002). Cases of 'failure to rescue' are often linked with difficulties relaying and interpreting information across occupational and professional boundaries. Standardised communication protocols have been recommended as a means of enabling the transmission of concise, salient information, licensing and empowering the individual to overcome established hierarchies in speaking out and asking for help. This paper critically examines the current discourse around such protocols. We find that there is a paucity of evidence regarding the complex relationship between social contexts, individual applications of these protocols and short- and long-term impact on safety and 'failure to rescue' rates. The paper highlights the complexities of the underlying power dynamics that are located within gendered and occupational hierarchies and explores the role of standardised communication protocols as a potential boundary object. The paper discusses the potential for these protocols to inter-relate and act as a mediating boundary object between nursing and medical staff, enabling understanding and sharing of cultural context.


Noonan-like phenotype in monozygotic twins with a duplication-deficiency of the long arm of chromosome 18 resulting from a maternal paracentric inversion.
We report on newborn monozygotic twins with a Noonan-like phenotype, and multiple congenital anomalies due to a monocentric recombinant chromosome 18. The mother carried a paracentric inversion of the long arm of chromosome 18, inv(18)(q21.1q22.3). Cytogenetic, fluorescent in situ hybridization, comparative genomic hybridization and DNA marker analyses allowed the delineation of the deleted (18q22.3-qter) and duplicated (18q12.1-q21.1) chromosomal regions in the recombinant chromosome 18, and suggest that this duplication-deletion chromosome 18 resulted from breakage of a dicentric recombinant chromosome 18 with subsequent reconstitution of telomeric sequences on the long arm. Marked variability is observed in the phenotypic expression of the same chromosomal anomaly in these monozygotic twins. The clinical findings of these patients are compared with those reported in proximal 18q-duplication and distal 18q-deletion patients. The clinical features of both infants are compatible with Noonan syndrome, suggesting that a locus for this syndrome may be located on the long arm of chromosome 18.


Delta opiate receptors account for the castration-induced unmasking of gonadotropin-releasing hormone binding sites in the rat pituitary.
Under control incubation conditions, gonadotropin-releasing hormone (GnRH) binds only a fraction of its receptors in rat-cultivated pituitary cells. Unmasking of the remaining receptors, which have been termed 'cryptic', requires drug- or peptide-induced protein kinase activation. Spontaneous masking however is not observed on pituitary cells sampled from castrated male rats, suggesting the presence of an intrinsic unmasking factor. Many endogenous factors could theoretically account for the effect. Here we attempted to identify the factor involved by taking advantage of their differential dependency upon second messengers and transduction cascades. Spontaneous unmasking of GnRH binding was found reversed by pertussis toxin (PTX), an inhibitor of alphai and alphao subunits of heterotrimeric G proteins, and by U73122, a phospholipase C (PLC) inhibitor. In contrast, desensitization of protein kinase C (PKC) or inhibition of tyrosine kinase by herbimycin were ineffective. Among endogenous pituitary factors able to unmask GnRH receptors in pituitary cells from normal male rats, as EGF, NPY or opiate peptides, only the latter were found to correspond to this transduction profile. In an attempt to characterize the pharmacology of opiate effects, naloxone (10 microM), a poorly selective opiate antagonist, restored masking of GnRH binding in cells from castrates. Only the delta antagonist naltrindole (1 microM) was able to mimick the action of naloxone. Conversely, when tested on cells from intact animals, morphine (10 microM), as well as dslet (1 microM) and met-ENK (10 nM), preferential delta agonists, but not dago and beta-endorphin or U50488 H and dynorphin, respectively micro and kappa agonists, were able to suppress masking. Among opioid peptides endogenous to the pituitary, only met-ENK was able to unmask cryptic receptors, an effect antagonized by naltrindole. We conclude that an opiate delta receptor subtype is endogenously activated in the pituitary of castrated male rats to prevent masking of GnRH binding.


Emission, distribution and toxicity of polycyclic aromatic hydrocarbons (PAHs) during municipal solid waste (MSW) and coal co-combustion.
Emission and distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) were investigated during municipal solid waste (MSW) and coal combustion alone and MSW/coal blend (MSW weight fraction of 25%) co-combustion within a temperature range of 500°C-900°C. The results showed that for all combustion experiments, flue gas occupied the highest proportion of total PAHs and fly ash contained more high-ring PAHs. Moreover, the 3- and 4-ring PAHs accounted for the majority of total PAHs and Ant or Phe had the highest concentrations. Compared to coal, MSW combustion generated high levels of total PAHs with the range of 111.28μg/g-10,047.22μg/g and had high toxicity equivalent value (TEQ). MSW/coal co-combustion generated the smallest amounts of total PAHs and had the lowest TEQ than MSW and coal combustion alone. Significant synergistic interactions occurred between MSW and coal during co-combustion and the interactions suppressed the formation of PAHs, especially hazardous high-ring PAHs and decreased the TEQ. The present study indicated that the reduction of the yield and toxicity of PAHs can be achieved by co-combustion of MSW and coal.


[Overweight in adolescent offspring of women with hyperglycemia during pregnancy].
To verify whether different hyperglycemia levels during pregnancy cause frequency differences in adolescent obesity and its morbidities in the offspring. Seventy-three children were divided into three groups according to maternal glucose tolerance: G1 (n=27) normal oral glucose tolerance test (OGTT) and daily glycemia (DG); G2 (n=23) normal OGTT and high DG; G3 (n=23) abnormal OGTT and DG (gestational diabetes mellitus; GDM). All underwent clinical evaluation (anthropometry) a questionnaire(neonatal data, eating habits), and determination of fasting serum glucose and lipid profile measurement. Analysis of variance (ANOVA) and the Goodmans test were used to compare the groups. G3 mothers showed higher fasting plasma glucose(FPG) and DG than G2 and G1(FPG: 93+/-10 vs 83+/-5 vs 78+/-10 mg/dL; DG: 104+/-12 vs 93+/-7 vs 85+/-9 mg/dL, respectively; P<0.001). G2 mothers had higher DG than G1 (93+/-7 vs 85+/-9 mg/dL; P<0.001). G3 offspring birthweight was higher than G1 and G2 (3,667+/-527 vs 3,167+/-565 and 3,282+/-401 g, respectively; P<0.05). More G3 offspring were overweight than G1 (52.2 vs 14.8%; P<0.05). Offspring of GDM mothers with fasting and daily hyperglycemia have higher birthweight and overweight frequency in adolescence. These children must be followed up from infancy.


Drivers׳ merging behavior data in highway work zones.
There have been growing research interests in finding a suitable work zone layout to improve work zone safety and traffic efficiency. This paper contains data supporting the research article entitled: Effects of work zone configurations and traffic density on performance variables and subjective workload (Shakouri et al., 2014 [1]). A full factorial experiment was conducted to compare the efficiency of two work zone configurations by using a driving simulator with two levels of work zone configuration, two levels of traffic density and three levels of sign placement as fixed factors. Seven female and 23 male participants completed the experiment. In this paper we present the data relating to demographic information of participants, driving simulator data and subjective workload evaluation of participants for each work zone.


Considering "Nonlinearity" Across the Continuum in Medical Education Assessment: Supporting Theory, Practice, and Future Research Directions.
The purpose of this article is to propose new approaches to assessment that are grounded in educational theory and the concept of "nonlinearity." The new approaches take into account related phenomena such as "uncertainty," "ambiguity," and "chaos." To illustrate these approaches, we will use the example of assessment of clinical reasoning, although the principles we outline may apply equally well to assessment of other constructs in medical education. Theoretical perspectives include a discussion of script theory, assimilation theory, self-regulated learning theory, and situated cognition. Assessment examples to include script concordance testing, concept maps, self-regulated learning microanalytic technique, and work-based assessment, which parallel the above-stated theories, respectively, are also highlighted. We conclude with some practical suggestions for approaching nonlinearity.


Enteric Fever in a Multicultural Canadian Tertiary Care Pediatric Setting: A 28-Year Review.
We undertook a 28-year review of enteric fever at a large tertiary care pediatric center. Most cases occurred in children who visited friends and relatives in the Indian subcontinent, and there was significant antibiotic resistance. Documented vaccination rates were low, and many cases also had evidence of delays in diagnosis and treatment.


The blistering diseases.
The intent and purpose of the authors is to familiarize the reader with the principles that govern the diagnosis and management of autoimmune mucocutaneous blistering diseases. The purpose was not to be all-inclusive but illustrative. There are several other blistering diseases that have not been discussed because of the limited scope of this article. Of these, toxic epidermal necrolysis, erythema multiforme, and the like warrant the same attention and early recognition. These are covered in different articles. For the same reasons, certain genetically linked blistering diseases have not been discussed.


Treatment success of rescue regimens after dual therapy failure in people living with HIV in a real-life setting.
Few data on management of two-drug regimen (2DR) failure in people living with HIV (PLWH) are available. Retrospective study of treatment-experienced PLWH on a 2DR who experienced virological failure (VF) [two consecutive viral loads (VLs) ≥50 copies/mL, single VL ≥1000 copies/mL, or antiretroviral therapy (ART) switch after single VL ≥50 copies/mL with previous blips] or discontinuation for toxicity (baseline). Integrase strand transfer inhibitor (INSTI)-based [one INSTI plus one nucleoside reverse transcriptase inhibitor (NRTI) (n = 78) or one non-NRTI (n = 20)] or boosted protease inhibitor (PI/b)-based [one PI/b plus one NRTI (n = 116) or one INSTI (n = 12)] 2DRs were included. Probabilities of treatment success (TS), VF and discontinuation for any other cause of rescue regimens were estimated by Kaplan-Meier curves. A stepwise Cox model was performed to assess predictors of TS. Overall, 226 PLWH were evaluated: at baseline, 144 individuals discontinued 2DR for toxicity and 82 had VF [median viraemia 81 (63-212) copies/mL]; 171 switched therapy (49.7% to triple regimen, 40.9% to different 2DR), while 55 (exclusively with VF) maintained failing regimens. Probabilities of 12- and 24-month TS were 75.6% and 64.7%, respectively. Higher TS probabilities were observed in individuals who switched ART at 2DR failure (P = 0.003) and PLWH who discontinued 2DR for toxicity (P = 0.008). Therapy switch was the only predictor of TS (P = 0.002). Overall probability of rescue regimens' TS introduced after 2DR failure is good. Prompt ART switch after 2DR failure is advisable.


Thrombotic microangiopathy after ABO-incompatible living donor liver transplantation: a case report.
Thrombotic microangiopathy (TMA) has rarely been reported in the setting of liver transplantation. Herein we have reported a successful case of TMA after ABO-incompatible living donor liver transplantation (LDLT) treated with plasma exchange and high-dose intravenous gamma-globulin infusion. A 50-year-old woman was diagnosed with hepatitis C virus-related cirrhosis. We performed an ABO-incompatible LDLT (group B to O) with preoperative plasma exchange to reduce the anti-B hemagglutinin titers to 1:8. The immunosuppressants consisted of tacrolimus, mycophenolate mofetil, and steroid. On postoperative day (POD) 8, her anti-B hemagglutinin titer suddenly increased to 1:64. The serum lactate dehydrogenase (LDH) level was grossly elevated (1518 IU/L). On POD 13, we suspected infection of an intra-abdominal hematoma (Serratia marcescens) which was drained surgically. On day 5 after the reoperation, thrombocytopenia developed with a platelet count of 3 x 10(4)/mm3. A peripheral blood film showed severe red blood cell (RBC) fragmentation. Thus, we made a clinical diagnosis of TMA and reduced the tacrolimus dose. We started intensive daily plasma exchange (4 L/d) with fresh frozen plasma and high-dose intravenous gamma-globulin infusions. One week thereafter, thrombocytopenia improved with reduced transfusion requirements. The peripheral blood film showed normal RBC morphology. The serum LDH returned to baseline levels. Four factors were considered to have caused TMA in this case: the prescription of tacrolimus, ABO-incompatible liver transplantation, bacterial infection, and surgical stress. These factors may have all contributed by causing significant endothelial injury and TMA.


[Immunomorphologic responses of regional lymph nodes and prognosis in patients with stage Ia pulmonary adenocarcinoma].
The relationship between postoperative prognosis and the immunomorphologic response of regional lymph nodes was examined in 50 patients with stage Ia peripheral bronchial adenocarcinoma and compared with 22 patients in stage Ib and II. Regarding paracortical lymphocyte hyperplasia, the prognosis of the responsive group in patients with stage Ia was significantly better than that of the non-responsive group; however, no definite relationship was found between follicular hyperplasia and prognosis. Follicular hyperplasia correlated with the size of the primary lesion or the distance from the site of the primary lesion. In stage Ib and II cases with metastasis to the pulmonary hilar lymph nodes, paracortical lymphocyte hyperplasia or follicular hyperplasia had no relation to the postoperative prognosis.


Nutritional status, physical performance and disability in the elderly of the Peruvian Andes.
Although nutritional status plays an important part in the physical performance and disability of older people, this relationship has been little studied in developing countries. A study on the effects of nutritional status on the physical performance and functional status of elderly people living in rural areas of the Peruvian Andes. The study concerned 222 people aged ≥65 years living in a rural area of the Peruvian Andes. The Mini-Nutritional Assessment (MNA) was used to classify participants as malnourished (MNA <= 17), at risk of malnutrition (MNA 18-23), or well-nourished (MNA>= 24). The short physical performance battery (SPPB) and six-minute walking test (6MWT) were used to measure participants' physical performance. Disabilities were investigated by assessing participants' self-reported difficulty in performing one or more basic activities of daily living (ADL), and instrumental activities of daily living (IADL). The prevalence of malnutrition was 9.4 %, and more than half of our samples were at risk of malnutrition. After adjusting for potential confounders, malnourished individuals performed significantly worse than the other MNA groups in the SPPB (p for trend=0.001), 6MWT and IADL (p for trend < 0.0001 for both outcomes), but not in the ADL (p for trend = 0.23). Taking the well-nourished for reference, and after adjusting for potential confounders, malnutrition was significantly associated with disability in IADL (OR 5.36, 95 % CI 1.02-56.94; p = 0.05), and poor performance in the 6MWT (OR 2.73, 95 % CI 1.06-12.08; p = 0.03) and SPPB (OR 4.94, 95 % CI 1.01-24.07; p = 0.04). Poor nutritional status was found significantly associated with poor physical performance and poor functional status in elderly Peruvian individuals.


The societal cost of depression: evidence from 10,000 Swedish patients in psychiatric care.
Depression cost studies have mainly taken a primary care perspective and should be completed with cost estimates from psychiatric care. The objectives of this study were to estimate the societal per-patient cost of depression in specialized psychiatric care in Sweden, and to relate costs to disease severity, depressive episodes, hospitalization, and patient functioning. Retrospective resource use data in inpatient and outpatient care for 2006-2008, as well as ICD-10 diagnoses and Global Assessment of Functioning (GAF), were obtained from the Northern Stockholm psychiatric clinic (covering half of Stockholm's population aged 18 years and above). As a complement, data from national registers on pharmaceuticals and sick leave were used in order to estimate the societal cost of depression. Based on 10,430 patients (63% women), the mean annual per-patient cost was €17,279 in 2008. The largest cost item was indirect costs due to productivity losses (88%), followed by outpatient care (6%). Patients with mild and severe depression had average costs of €14,200 and €21,500, respectively. Total costs were substantially higher during depressive episodes, among patients with co-morbid psychosis or anxiety, for hospitalized patients, and for patients with poor functioning. Primary care costs and costs for reduced productivity at work were not included. The main cost item among depression patients in psychiatric care was indirect costs. Costs were higher than previously reported for primary care, and strongly related to hospitalization, depressive episodes, and low functioning. This suggests that effective treatment that avoids depressive episodes and hospitalization may reduce society's costs for depression.


Manipulation of phototransductive membrane turnover by crab photoreceptors in vitro: effects of two protein kinase activators, SC-9 and phorbol ester in the presence of a protein phosphatase inhibitor, okadaic acid.
1. Retinae of crabs, Leptograpsus variegatus, held on a 12:12 h light-dark cycle were prepared for culture in vitro shortly before light-off. After an hour in darkness to permit the assembly of "night" rhabdoms, retinae were exposed to various combinations of drugs: 1 microM okadaic acid (OKA); 60 microM SC-9; 10 microM phorbol, 12,13-diacetate (PDA). 2. The effects of the specific protein phosphatase inhibitor, OKA, are confirmed as light-dependent. Rhabdom sizes were not compromised by OKA, nor by either of the two protein kinase activators, SC-9 or PDA when each was deployed alone in darkness. 3. In combination with OKA, PDA induced demolition of rhabdoms by abnormal macropinocytosis of microvillar membranes. 4. Combined with OKA, SC-9 induced a transient reduction of rhabdoms, followed by overgrowth to abnormal sizes. Overgrowth was blocked by the transcription inhibitor actinomycin D. 5. Disparate consequences of combining OKA with SC-9 or PDA imply that more than one protein kinase C may be involved.


A Business Analytics Software Tool for Monitoring and Predicting Radiology Throughput Performance.
Business analytics (BA) is increasingly being utilised by radiology departments to analyse and present data. It encompasses statistical analysis, forecasting and predictive modelling and is used as an umbrella term for decision support and business intelligence systems. The primary aim of this study was to determine whether utilising BA technologies could contribute towards improved decision support and resource management within radiology departments. A set of information technology requirements were identified with key stakeholders, and a prototype BA software tool was designed, developed and implemented. A qualitative evaluation of the tool was carried out through a series of semi-structured interviews with key stakeholders. Feedback was collated, and emergent themes were identified. The results indicated that BA software applications can provide visibility of radiology performance data across all time horizons. The study demonstrated that the tool could potentially assist with improving operational efficiencies and management of radiology resources.


Online NIR Analysis and Prediction Model for Synthesis Process of Ethyl 2-Chloropropionate.
Online near-infrared spectroscopy was used as a process analysis technique in the synthesis of 2-chloropropionate for the first time. Then, the partial least squares regression (PLSR) quantitative model of the product solution concentration was established and optimized. Correlation coefficient (R (2)) of partial least squares regression (PLSR) calibration model was 0.9944, and the root mean square error of correction (RMSEC) was 0.018105 mol/L. These values of PLSR and RMSEC could prove that the quantitative calibration model had good performance. Moreover, the root mean square error of prediction (RMSEP) of validation set was 0.036429 mol/L. The results were very similar to those of offline gas chromatographic analysis, which could prove the method was valid.


Chronic prenatal exposure to carbamazepine and behavior effects on mice offspring.
The purpose of this study was to assess the impact of chronic prenatal exposure to a therapeutic dose of carbamazepine on the behavior of mice offspring in a randomized, placebo-controlled manner. Twenty-eight C3H/He mice were assigned randomly to treatment groups that were given food that contained either carbamazepine (25 mg in 10 g food) or a placebo for 1 week before mating and throughout gestation. Adult offspring from eight litters of each group were evaluated for standard tasks for motor, arousal/motivation, anxiety, and cognition. Statistical comparisons included analysis of variance and the Fisher exact test. Compared with the placebo group, there were no significant differences among the carbamazepine offspring in the duration of gestation, litter size, and birth weights. Fewer locomotor chamber movements were recorded in the carbamazepine group than in the placebo-exposed group at postnatal day 21 (469 vs 555 counts for 60 minutes, P<.03) and as adults (510 vs 688 counts for 60 minutes, P<.03) Coordination, balance, and exploratory behavior did not differ between exposure groups. A startle response from auditory arousal was decreased in carbamazepine-exposed adults (1.4% vs 21.9%, P<.03). Performances on anxiety/motivation tasks and on learning/memory tasks revealed no significant differences between exposure groups. Although prenatal exposure induced subtle arousal effects and slower locomotor activity, carbamazepine did not have an impact on coordination, cognition, or responses to anxiety-provoking conditions. Correlation in humans is recommended.


A randomized, double-blind, placebo-controlled, multicenter study assessing the efficacy of magnesium oxide monohydrate in the treatment of nocturnal leg cramps.
Magnesium supplements are widely used for prophylaxis and treatment of nocturnal leg cramps (NLC). However, there is little evidence in support of their effectiveness. The main impediment stems from the lack of assessments of cellular absorption. In the current study, we tested the efficacy and safety of a magnesium supplement - magnesium oxide monohydrate (MOMH), for which increased cellular absorption rates were demonstrated in an ex-vivo setting. A randomized, double-blind, placebo-controlled multicenter study was conducted in hospitals and outpatient clinics in Ukraine, from February to August 2018. Eligible subjects received a capsule with MOMH 226 mg or placebo, once daily, at bedtime, for a 60-day period. The assessed parameters included frequency and duration of NLC episodes, quality of sleep, NLC-induced pain and quality of life sub-scores. The Fisher's Exact Test for comparison of groups by categorical variables was used. The Student's test or Mann-Whitney test were used for between-group comparison at different timepoints. ANCOVA followed by contrast analysis was used for comparison of groups at the end of the study. 175 (81%) out of 216 initially screened subjects completed the study. The number of NLC episodes has significantly decreased by the end of the study period as compared to baseline in both groups (p < 0.001 for both). There was a significant between-group difference in the magnitude of reduction in NLC episodes (p = 0.01), indicating a higher decrease in the MOMH group as compared to the placebo group (- 3.4 vs - 2.6, respectively). In addition, MOMH treatment resulted in a greater reduction in NLC duration (p < 0.007) and greater improvement in sleep quality (p < 0.001) as compared to placebo. MOMH was shown to be effective in the treatment of NLC as well as safe and well-tolerated. NCT03807219 , retrospectively registered on January 16, 2019.


Advances in High-Field MRI.
MRI techniques and systems have evolved dramatically over recent years. These advances include higher field strengths, new techniques, faster gradients, improved coil technology, and more robust sequence protocols. This article reviews the most commonly used advanced MRI techniques, including diffusion-weighted imaging, magnetic resonance spectrography, diffusion tensor imaging, and cerebrospinal fluid flow tracking.


Telomere transcription in ageing.
Telomeres, the ends of eukaryotic chromosomes, play a central role in the control of cellular senescence and organismal ageing and need to be protected in order to avoid being recognised as damaged DNA and activate DNA damage response pathways. Dysfunctional telomeres arise from critically short telomeres or altered telomere structures, which ultimately lead to replicative cellular senescence and chromosome instability: both hallmarks of ageing. The observation that telomeres are transcribed led to the discovery that telomeric transcripts play important roles in chromosome end protection and genome stability maintenance. Recent evidence indicates that particular long non-coding (nc)RNAs transcribed at telomeres, namely TElomeric Repeat-containing RNA (TERRA) and telomeric damage-induced long ncRNAs (tdilncRNA), play key roles in age-related pathways by actively orchestrating the mechanisms known to regulate telomere length, chromosome end protection and DNA damage signalling. Here, we provide a comprehensive overview of the telomere transcriptome, outlining how it functions as a regulatory platform with essential functions in safeguarding telomere integrity and stability. We next review emerging antisense oligonucleotides therapeutic strategies that target telomeric ncRNAs and discuss their potential for ameliorating ageing and age-related diseases. Altogether, this review provides insights on the biological relevance of telomere transcription mechanisms in human ageing physiology and pathology.


Disparity in the temporal appearance of methamphetamine-induced apoptosis and depletion of dopamine terminal markers in the striatum of mice.
Methamphetamine (METH) causes damage in the striatum at pre- and post-synaptic sites. Exposure to METH induces long-term depletions of dopamine (DA) terminal markers such as tyrosine hydroxylase (TH) and DA transporters (DAT). METH also induces neuronal apoptosis in some striatal neurons. The purpose of this study is to demonstrate which occurs first, apoptosis of some striatal neurons or DA terminal toxicity in mice. This is important because the death of striatal neurons leaves the terminals in a state of deafferentation. A bolus injection (i.p.) of METH (30 mg/kg) induces apoptosis (TUNEL staining) in approximately 25% of neurons in the striatum at 24 h after METH. However, in contrast to apoptosis, depletion of TH (Western blotting) begins to appear at 24 h after METH in dorsal striatum while the ventral striatum is unaffected. The peak of TH depletion (approximately 80% decrease relative to control) occurs at 48 h after METH. Autoradiographic analysis of DAT sites showed that depletion begins to appear 24 h after METH and peaks at 2 days (approximately 60% depletion relative to control). Histological analysis of the induction of glial fibrillary acidic protein (GFAP) by METH in striatal astrocytes revealed an increase at 48 h after METH that peaked at 3 days. These data demonstrate that striatal apoptosis precedes the depletion (toxicity) of DA terminal markers in the striatum of mice, suggesting that the ensuing state of deafferentation of the DA terminals may contribute to their degeneration.


Age and blood pressure determine vasodepressor response to sodium nitroprusside.
Twenty-two patients, aged 33-72 years, with uncomplicated essential hypertension were given sequential incremental intravenous infusions of sodium nitroprusside, each of 10 min duration, to examine the determinants of the vasodepressor response. Changes in mean arterial pressure (delta MAP), heart rate (delta HR), and plasma norepinephrine (delta nc) were determined at the end of each infusion period. The slopes of the dose-response curves obtained were directly proportional to predrug blood pressure (p less than 0.0001) and inversely proportional to baroreflex sensitivity as measured by the slope of the delta HR vs. delta MAP relationship (p = 0.0007). Baroreflex sensitivity was in turn inversely proportional to, and approximately equally dependent on, predrug blood pressure and age (p = 0.0116). Thus, the slopes of the dose-response curves were determined by both predrug blood pressure and patient age. The relationship was such that predrug blood pressure accounted for approximately 75% of the variability in the slope of the dose-response curve, and age for only 25%. This suggests that the age-related reduction in baroreflex sensitivity is mechanistically different from the hypertension-related reduction and is of less importance in modifying homeostatic responses to vasodilation.


White matter tractography by anisotropic wavefront evolution and diffusion tensor imaging.
Determination of axonal pathways provides an invaluable means to study the connectivity of the human brain and its functional network. Diffusion tensor imaging (DTI) is unique in its ability to capture the restricted diffusion of water molecules which can be used to infer the directionality of tissue components. In this paper, we introduce a white matter tractography method based on anisotropic wavefront propagation in diffusion tensor images. A front propagates in the white matter with a speed profile governed by the isocontour of the diffusion tensor ellipsoid. By using the ellipsoid, we avoid possible misclassification of the principal eigenvector in oblate regions. The wavefront evolution is described by an anisotropic version of the static Hamilton-Jacobi equation, which is solved by a sweeping method in order to obtain correct arrival times. Pathways of connection are determined by tracing minimum-cost trajectories using the characteristic vector field of the resulting partial differential equation. A validity index is described to rate the goodness of the resulting pathways with respect to the directionality of the tensor field. Connectivity results using normal human DTI brain images are illustrated and discussed. We also compared our method with a similar level set-based tractography technique, and found that the anisotropic evolution increased the validity index of the obtained pathways by 18%.