(Ir)reconcilable differences? Local reactions to provincial neoliberal educational reform.
In this case study, we explore the intersections of neoliberal educational reform and the everyday experiences of people living in a rural region in northern British Columbia, Canada. Reflecting on the provincial Ministry of Education's Strategic Plan, we explore one region's responses to a set of provincial promises, which include providing regional school districts with more autonomy and control over the delivery of education services and a mandate for a balanced budget. The region faced declining student enrolments and funding shortfalls. As a cost-saving measure, the local school district in the region launched a four-day school week. We used ethnographic fieldwork techniques to examine a set of local practices and consequences that arose following the implementation of this measure. The findings demonstrate how provincial promises of educational reform can conflict with local educational needs and create a set of problematic everyday realities with repercussions on youth health, amplifying health inequalities that are irreconcilable with the purported goals of advancing the interests of students and society.


Long-term outcome and prognostic factors of idiopathic membranous nephropathy in the Chinese population.
Idiopathic membranous nephropathy (IMN) is a representative form of nephrotic syndrome in China. Although IMN is thought to run a more benign course in Asian patients than in the Caucasian population, there has been no persuasive study to determine the long-term prognosis and risk factors for IMN in the Chinese population. A retrospective chart review. All patients admitted to Nanjing Institution of Nephrology from January 1985 to December 2007 with biopsy-proven IMN were enrolled. The primary outcome was the renal survival rate and risk factors at renal biopsy. A total of 217 patients were included in the study, and the overall renal survival rates were 96.9%, 93.5%, and 86.6% at 5, 10, and 15 years after renal biopsy, respectively. When the clinical features at biopsy were evaluated, patients with hypertension (p = 0.023), decreased eGFR (p < 0.001), nephrotic-range proteinuria (p = 0.047), elevated urinary NAG (p = 0.045) and RBP (p = 0.007) had a worse prognosis. Cox multivariate analysis showed that decreased eGFR and chronic tubulointerstitial lesion were independent risk factors for ESRF (end-stage renal failure). IMN is a disease with a comparatively good prognosis in the Chinese population, with a renal survival rate of more than 90% at 10 years after renal biopsy. Decreased eGFR at biopsy and chronic tubulointerstitial lesion are independent risk factors of ESRF. Partial or complete remission of proteinuria improved the prognosis.


Achieving operational hydrologic monitoring of mosquitoborne disease.
Mosquitoes and mosquitoborne disease transmission are sensitive to hydrologic variability. If local hydrologic conditions can be monitored or modeled at the scales at which these conditions affect the population dynamics of vector mosquitoes and the diseases they transmit, a means for monitoring or modeling mosquito populations and mosquitoborne disease transmission may be realized. We review how hydrologic conditions have been associated with mosquito abundances and mosquitoborne disease transmission and discuss the advantages of different measures of hydrologic variability. We propose that the useful application of any measure of hydrologic conditions requires additional consideration of the scales for both the hydrologic measurement and the vector control interventions that will be used to mitigate an outbreak of vectorborne disease. Our efforts to establish operational monitoring of St. Louis encephalitis virus and West Nile virus transmission in Florida are also reviewed.


Evidence-based therapy for cutaneous sarcoidosis.
Although healthcare providers have arrived at a relatively comfortable zone of accepted clinical practice in the management of cutaneous sarcoidosis, virtually every treatment is based on minimal evidence-based data and relies almost exclusively on anecdotal information. Although it would be convenient to blame this state of affairs on the lack of certainty about disease aetiology, the unavoidable fact is that little has been executed, even in the realm of well designed comparative trials. Nonetheless, worldwide accepted standard therapies for sarcoidosis include the administration of corticosteroids, antimalarials and methotrexate. A stepwise approach to patient care is appropriate, and potent topical corticosteroids (e.g. clobetasol) or repeated intralesional injections of triamcinolone (3-10 mg/mL) may be all that is needed in mild skin-limited disease. In patients requiring systemic therapy for recalcitrant or deforming skin lesions (or for widespread disease), corticosteroids (e.g. prednisone 40-80 mg/day, tapered accordingly) used alone or in combination with antimalarials or methotrexate may be indicated. Antimalarials and methotrexate are considered second-line interventions and may be used as monotherapy for steroid-resistant sarcoidosis or in patients unable to tolerate steroids. Given the concern regarding ocular toxicity, the maximum dosages of chloroquine and hydroxychloroquine should not exceed 3.5 and 6.5 mg/kg/day, respectively. Methotrexate is given in weekly doses of 10-30 mg, with the caveat that haematological, gastrointestinal, pulmonary and hepatic toxicities are possible. Despite universal acceptance as standard care, the aforementioned treatments often result in an incomplete clinical response or unacceptable adverse events. In such situations, more innovative treatment options may be used. Treatments that may well gain widespread future use include the tumour necrosis factor-alpha inhibitors infliximab and adalimumab. Experience is limited, but early reports are promising. Infliximab is administered via intravenous infusion at doses of 3-10 mg/kg at 0, 2 and 6 weeks and as indicated thereafter, whereas adalimumab is injected subcutaneously at doses of 40 mg either weekly or every 2 weeks. Because adalimumab is not approved for the management of sarcoidosis, the optimum dose administration interval is uncertain. However, it has been given in both weekly and every other week regimens. Isotretinoin, 0.5-2 mg/kg/day, has been used successfully in a handful of reported cases. However, the teratogenic potential of isotretinoin is often prohibitive considering that the primary demographic group likely to develop sarcoidosis is women of childbearing potential. Thalidomide at dosages of 50 to >400 mg/day has limited, albeit promising, supporting data. However, access is restricted in many countries because of a deserved pregnancy category X rating. Melatonin (20 mg/day) and allopurinol (100-300 mg/day) are not well studied in cutaneous sarcoidosis, and the clinical experience with tetracycline derivatives has been mixed. That said, there are compelling reports of therapeutic benefit with both doxycycline and minocycline. Because neither of these agents is associated with the severe toxicity of cytotoxic drugs, they may serve as effective therapy in some patients. Pentoxifylline (400 mg three times daily) has been of use in a small number of reported cases of pulmonary sarcoidosis, but there are no reports on its use in patients with primarily cutaneous disease. Both ciclosporin and chlorambucil have been largely abandoned given their associated toxicity and disappointingly unreliable efficacy. Finally, laser therapy is a newer modality that may provide patients with a quick and non-invasive treatment option for cutaneous sarcoidosis.


3D electron dose calculation using a Voxel based Monte Carlo algorithm (VMC).
A new model for calculating electron beam dose has been developed. The algorithm is based on a two- or three-dimensional geometry defined by computerized tomography (CT) images. The Monte Carlo technique was used to solve the electron transport equation. However, in contrast to conventional Monte Carlo models (EGS4) several approximations and simplifications in the description of elementary electron processes were introduced reducing in this manner the computational time by a factor of about 35 without significant loss in accuracy. The Monte Carlo computer program does not need any precalculated data. The random access memory required is about 16 Mbytes for a 128(2) X 50 matrix, depending on the resolution of the CT cube. The Voxel Monte Carlo model (VMC) was tested in comparison to calculations by EGS4 and the "Hogstrom algorithm" (MDAH) using several fictive phantoms. In all cases a good coincidence has been found between EGS4 and VMC, especially near tissue inhomogeneities, whereas the MDAH algorithm has produced dose underestimations of up to 40%.


Theory of pattern formation of metallic microparticles in poorly conducting liquids.
We develop a continuum theory of self-assembly and pattern formation in metallic microparticles immersed in a poorly conducting liquid in a dc electric field. The theory is formulated in terms of conservation laws for the densities of immobile particles (precipitate) and bouncing particles (gas) coupled to the Navier-Stokes equation for the liquid. This theory successfully reproduced the correct topology of the phase diagram and primary patterns observed in the experiment [Phys. Rev. Lett. 90, 114301 (2003)]]: static crystals, honeycombs, dynamic pulsating rings, and rotating multipetal vortices.


Pharmacokinetic interaction of the direct renin inhibitor aliskiren with furosemide and extended-release isosorbide-5-mononitrate in healthy subjects.
This study investigated the pharmacokinetics, safety, and tolerability of aliskiren administered alone or in combination with either the loop diuretic furosemide or an oral extended-release formulation of isosorbide-5-mononitrate (ISMN). In separate studies, 22 healthy subjects (ages 18-45 years) received either ISMN 40 mg or furosemide 20 mg once-daily for 3 days followed by a 3-day washout. Subjects then received aliskiren 300 mg once-daily for 7 days followed by combination therapy for 3 days. Pharmacokinetic assessments were taken at regular intervals over 24 h after dosing on the last day of each treatment period. At steady state, aliskiren AUC(tau) was decreased by 7% (geometric mean ratio [90% CI], 0.93 [0.84, 1.04]), and C(max) by 20% (0.80 [0.65, 0.97]) with furosemide coadministration compared with aliskiren administration alone. Aliskiren coadministration reduced furosemide AUC(tau) by 28% (0.72 [0.64, 0.81]) and C(max) by 49% (0.51 [0.39, 0.66]) compared with furosemide alone. Coadministration of aliskiren and ISMN was associated with only minor changes in the pharmacokinetic parameters of aliskiren (AUC(tau) 1.03 [0.90, 1.18]; C(max) 0.94 [0.69, 1.29]) and ISMN (AUC(tau) 0.88 [0.71, 1.10]; C(max) 0.94 [0.79, 1.13]). Headache and dizziness were the most common adverse events in both studies; dizziness and BP values below normal (SBP < 90 and/or DBP < 50 mmHg) were more frequent with aliskiren and ISMN coadministration than with either agent alone. Coadministration of aliskiren and ISMN had no clinically relevant effect on either aliskiren or ISMN pharmacokinetics. In conclusion, coadministration of aliskiren and furosemide reduced furosemide exposure and had a minor effect on aliskiren pharmacokinetics. The clinical significance of reduced systemic exposure to furosemide during coadministration of aliskiren is uncertain.


Frequency of HgbA1c testing as a measure of diabetes care in Louisiana.
The Frequency of HgbA1c Testing Project is a continuous quality improvement project designed to measure and improve the frequency of HgbA1c testing among Medicare diabetic patients in Louisiana. Louisiana Medicare Part B electronic claims data from June 1995 to December 1996 were used to construct diabetes quality of care type indicators. A total of 47,270 Medicare, Part B eligible, non-HMO, diabetic patients were identified and studied. The statewide baseline results indicated that only 24% of the Medicare diabetic patients were covered by an HgbA1c test within 180 days from their last physician office visit. Twenty-one percent (21%) of practicing primary care physicians had none of their diabetic patients tested for HgbA1c within 180 days from the patient's last office visit. Overall, only 18% of all primary care physicians "seized" the opportunity to perform an HgbA1c test within this time frame. Twenty-two percent (22%) of Louisiana primary care physicians had never seized the opportunity to check for HgbA1c on eligible patients. Interventions and strategies are being implemented statewide in order to improve the low HgbA1c testing rates.


CT vs MRCP: optimal classification of IPMN type and extent.
Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are being diagnosed with increased frequency. CT scanning commonly serves as the primary imaging modality before surgery. We hypothesized MRCP provides better characterization of IPMN type/extent, which more closely matches actual pathology. Of 214 patients treated with IPMN (1991-2006), 30 had both preoperative CT and MRCP. Of these, 18 met imaging study criteria. Independent readers performed retrospective, blinded analyses using standardized criteria for IPMN type and extent. A ductal connection was detected on 73% of MRCP scans and only 18% of CT. IPMN type was classified differently in seven (39%); four (22%) of which were read on CT as having main duct involvement where this was not appreciated on MRCP or found on surgical pathology. MRCP showed multifocal disease in 13(72%) versus only 9(50%) on CT. A different disease distribution was seen in 9(50%). Finally, 101 branch lesions were identified on MRCP compared to 46 on CT. CT falls short of MRCP in detecting a ductal connection, estimating main duct involvement, and identification of small branch duct cysts. These factors influence diagnostic accuracy, cancer risk stratification and operative strategy. MRCP should be employed for optimal management of patients with IPMN.


[Peripheral NK/T-cell lymphoma].
Peripheral T-cell lymphomas comprise 8% of the malignant lymphomas in Germany. About 25% of these cases present primarily in extranodal localizations. Such localizations are typical for the respective disease and form the basis for the classification of extranodal peripheral T-cell lymphoma. The morphology, immunophenotype and lineage specificity of the tumor cells (originating from T- or NK-cells) is only secondary for the classification. Extranodal NK/T-cell lymphomas of the nasal type are characterized by an angiocentric growth pattern and large confluent areas of necrosis. In addition, there is a clonal infection by Epstein-Barr virus in the T-lymphocytes. In the differential diagnosis, B-cell lymphomas are more frequent at all localizations than T- or NK-cell lymphomas.


Concurrent and predictive relationships between compulsive internet use and substance use: findings from vocational high school students in China and the USA.
Compulsive Internet Use (CIU) has increasingly become an area of research among process addictions. Largely based on data from cross-sectional studies, a positive association between CIU and substance use has previously been reported. This study presents gender and country-specific longitudinal findings on the relationships between CIU and substance use. Data were drawn from youth attending non-conventional high schools, recruited into two similarly implemented trials conducted in China and the USA. The Chinese sample included 1,761 students (49% male); the US sample included 1,182 students (57% male) with over half (65%) of the US youth being of Hispanic ethnicity. Path analyses were applied to detect the concurrent and predictive relationships between baseline and one-year follow-up measures of CIU level, 30-day cigarette smoking, and 30-day binge drinking. (1) CIU was not positively related with substance use at baseline. (2) There was a positive predictive relationship between baseline CIU and change in substance use among female, but not male students. (3) Relationships between concurrent changes in CIU and substance use were also found among female, but not male students. (4) Baseline substance use did not predict an increase in CIU from baseline to 1-year follow-up. While CIU was found to be related to substance use, the relationship was not consistently positive. More longitudinal studies with better measures for Internet Addiction are needed to ascertain the detailed relationship between Internet addiction and substance use.


Reproductive skew in the polygynandrous acorn woodpecker.
Reproductive skew models, which focus on the degree to which reproduction is shared equally (low skew) or monopolized by a single individual (high skew) within groups, have been heralded as providing a general unifying framework for understanding the factors determining social evolution. Here, we test the ability of optimal skew, or "transactional," models, which predict the level of skew necessary to promote stable associations of dominants and subordinates, rather than independent breeding, to predict reproductive partitioning in the acorn woodpecker (Melanerpes formicivorus). This species provides a key test case because only a few vertebrates exhibit polygynandry (multiple breeders of both sexes within a group). Contrary to the predictions of the models, joint-nesting females share reproduction more equitably than expected, apparently because egg destruction and the inability of females to defend their eggs from cobreeders eliminate any possibility for one female to control reproduction. For males, however, reproductive skew is high, with the most successful male siring over three times as many young as the next most successful male. Although this result is consistent with optimal skew models, other aspects of male behavior are not; in particular, the reproductively most successful male frequently switches between nests produced by the same set of cobreeders, and we were unable to detect any phenotypic correlate of success. These results are consistent with an alternative null model in which cobreeder males have equal chance of paternity, but paternity of offspring within broods is nonindependent as a consequence of female, rather than male, control.


The development of the PROMPT (PRescribing Optimally in Middle-aged People's Treatments) criteria.
Whilst multimorbidity is more prevalent with increasing age, approximately 30% of middle-aged adults (45-64 years) are also affected. Several prescribing criteria have been developed to optimise medication use in older people (≥65 years) with little focus on potentially inappropriate prescribing (PIP) in middle-aged adults. We have developed a set of explicit prescribing criteria called PROMPT (PRescribing Optimally in Middle-aged People's Treatments) which may be applied to prescribing datasets to determine the prevalence of PIP in this age-group. A literature search was conducted to identify published prescribing criteria for all age groups, with the Project Steering Group (convened for this study) adding further criteria for consideration, all of which were reviewed for relevance to middle-aged adults. These criteria underwent a two-round Delphi process, using an expert panel consisting of general practitioners, pharmacists and clinical pharmacologists from the United Kingdom and Republic of Ireland. Using web-based questionnaires, 17 panellists were asked to indicate their level of agreement with each criterion via a 5-point Likert scale (1 = Strongly Disagree, 5 = Strongly Agree) to assess the applicability to middle-aged adults in the absence of clinical information. Criteria were accepted/rejected/revised dependent on the panel's level of agreement using the median response/interquartile range and additional comments. Thirty-four criteria were rated in the first round of this exercise and consensus was achieved on 17 criteria which were accepted into the PROMPT criteria. Consensus was not reached on the remaining 17, and six criteria were removed following a review of the additional comments. The second round of this exercise focused on the remaining 11 criteria, some of which were revised following the first exercise. Five criteria were accepted from the second round, providing a final list of 22 criteria [gastro-intestinal system (n = 3), cardiovascular system (n = 4), respiratory system (n = 4), central nervous system (n = 6), infections (n = 1), endocrine system (n = 1), musculoskeletal system (n = 2), duplicates (n = 1)]. PROMPT is the first set of prescribing criteria developed for use in middle-aged adults. The utility of these criteria will be tested in future studies using prescribing datasets.


Normal segregation of a foreign-species chromosome during Drosophila female meiosis despite extensive heterochromatin divergence.
The abundance and composition of heterochromatin changes rapidly between species and contributes to hybrid incompatibility and reproductive isolation. Heterochromatin differences may also destabilize chromosome segregation and cause meiotic drive, the non-Mendelian segregation of homologous chromosomes. Here we use a range of genetic and cytological assays to examine the meiotic properties of a Drosophila simulans chromosome 4 (sim-IV) introgressed into D. melanogaster. These two species differ by ∼12-13% at synonymous sites and several genes essential for chromosome segregation have experienced recurrent adaptive evolution since their divergence. Furthermore, their chromosome 4s are visibly different due to heterochromatin divergence, including in the AATAT pericentromeric satellite DNA. We find a visible imbalance in the positioning of the two chromosome 4s in sim-IV/mel-IV heterozygote and also replicate this finding with a D. melanogaster 4 containing a heterochromatic deletion. These results demonstrate that heterochromatin abundance can have a visible effect on chromosome positioning during meiosis. Despite this effect, however, we find that sim-IV segregates normally in both diplo and triplo 4 D. melanogaster females and does not experience elevated nondisjunction. We conclude that segregation abnormalities and a high level of meiotic drive are not inevitable byproducts of extensive heterochromatin divergence. Animal chromosomes typically contain large amounts of noncoding repetitive DNA that nevertheless varies widely between species. This variation may potentially induce non-Mendelian transmission of chromosomes. We have examined the meiotic properties and transmission of a highly diverged chromosome 4 from a foreign species within the fruitfly Drosophila melanogaster. This chromosome has substantially less of a simple sequence repeat than does D. melanogaster 4, and we find that this difference results in altered positioning when chromosomes align during meiosis. Yet this foreign chromosome segregates at normal frequencies, demonstrating that chromosome segregation can be robust to major differences in repetitive DNA abundance.


Photodynamic therapy--mechanism and employment.
Photodynamic terapy (PDT) is a new treatment for a wide variety of malignancies and premalignant dysplasias, as well as some non-cancer indications. Therapeutic response to PTD is achieved through the activation of non-toxic photosensitiser located within neoplastic tissue, using visible light tuned to the appropriate absorption band of the photosensitiser molecule. This produces cytotoxic free radical such as singlet oxigen, which result in local photo-oxidation, cell damage and destruction of the tumour cells. Systemic administration of photosensitisers has been used with endoscopic light exposure to treat a variety of internal malignances. A topical drug delivery is used in the skin deseases treatment. The selective distribution of photosensitiser in the target tissue is the fundamental to the process of PDT. This tissue specific photosensitation and normal tissue sparing results in good healing and often very good cosmetic results. Peterson PTD can be used for the treatment of cutaneous lesions (e.g., SCC, BCC, Bowen's disease, mycosis fungoides, erythroplasia of Queyrat, Gorlin's Syndrome, actinic keratoses), lower genital tract neoplasia (VIN and CIN), gastrointestinal tumours, etc., as well as nononcological indications (e.g., acne, condyloma acuminatum, lichen planus, psoriasis, vitiligo, vulval lichen sclerosus, warts and verrucae).


Regulation of ABI5 turnover by reversible post-translational modifications.
Post-translational modifications (PTMs) such as phosphorylation, ubiquitination, and sumoylation play significant roles in regulating abscisic acid (ABA) signaling. The targets for PTM are usually transcriptional regulators such as Abscisic acid Insensitive 5 (ABI5). PTM regulate ABI5 stability as well as activity. The abundance of ABI5 is tightly controlled by the ubiquitination-26S proteasome system. E3 ubiquitin ligases such as KEG negatively regulate ABA signaling by promoting ABI5 ubiquitination and subsequent degradation by the 26S proteasome. In our recent study we demonstrated that, in the absence of ABA, KEG-mediated turnover of ABI5 occurs within the cytoplasm. Whereas ubiquitination promotes ABI5 degradation, sumoylation prohibits degradation of the transcription factor. While phosphorylation has been shown to regulate ABI5 activity, our studies and others suggest that the phosphorylation status of ABI5 does not play a significant role in modulating ABI5 turnover.


Stabilization of ketone and aldehyde enols by formation of hydrogen bonds to phosphazene enolates and their aldol products.
Solution properties of enolates generated using the phosphazene (Schwesinger) base P4-tBu were investigated by NMR spectroscopy. With a full equivalent of base the benzyl ketones 1a and 1b, the acetophenone 2, the arylacetaldehyde 1c, and the methyl arylacetate 1d formed the expected "naked" (P4H+) enolates 3 and 7. However, at a half-equivalent of base the ketones 1a and 1b as well as the aldehyde 1c formed solutions of stable hydrogen-bonded dimeric (enol-enolate) structures (4). The acetophenone 2, on the other hand, forms only traces of the H-bonded dimer 8 during deprotonation of 2. The thermodynamic product was the isomeric self-aldol condensation product 12. The mechanism of this condensation was elucidated by low temperature rapid-injection (RI) NMR spectroscopy. Solutions of 8 stable enough for NMR characterization could be transiently generated by semiprotonation of the enolate 7 with HCl.OEt2 at -130 degrees C using RINMR. The ester enolate 1d gave no trace of 4d even on a time scale as short as a few seconds at -130 degrees C either during the semideprotonation of 1d, or during semiprotonation of the enolate 3d. Long-lived solutions of the enols derived from 1a, 1b, 1c, and 2 (but not 1d) could be produced by full protonation of the phosphazene enolates with HCl.OEt2 at low temperature.


Eastbourne Miami-J Protocol: a Pilot Study for the Care of Cervical Injuries in the Community.
PURPOSE OF THE STUDY The aim of this pilot study was to develop The Eastbourne Miami-J Protocol for care of cervical injuries within the community. Led by orthopaedic senior practitioners, a multidisciplinary approach was developed to provide education and collar care for patients on a weekly basis. MATERIALS AND METHODS A total of 51 patients (17 male and 33 female), mean age 74 years (21 to 95) with CT confirmed cervical injuries during November 2010 and May 2014 followed the Eastbourne Miami-J Protocol. RESULTS Patients required collar care on average for 7.25 weeks. Thirty-two patients had single level cervical injuries with C2 the commonest. Complications included: 6 patients with psychosocial issues; 10 patients with skin erythema due to ill-fitting collars and 2 patients with skin breakdown requiring dressings. CONCLUSION The Eastbourne Miami-J protocol demonstrates that a multidisciplinary approach, championed by the casting department, can provide care for patients with cervical injuries within the community. cervical spine, C-spine, cervical collar, community, rehabilitation.


Self-assessment of health status among lesbian, gay, and bisexual cancer survivors in the United States.
Research is lacking for understanding the health disparities in cancer survivorship in the lesbian, gay, and bisexual (LGB) population in the United States. Self-reported health status is used as a predictor of health disparities. This secondary data analysis study used 2018 Behavioral Risk Factor Surveillance System data to analyze cancer survivorship characteristics by sexual orientation and sex through the use of logistic regressions. Overall, 17,656,329 US cancer survivors were included in this study after weighting, with percentage estimates of 1.52% for gays/lesbians and 1.41% for bisexuals. LGB participants were younger and more ethnically diverse. Significantly, bisexuals had current smoking (32.3% vs 13.6%) and binge drinking rates (17.1% vs 9.1%) twice those of heterosexuals; 16.6% of bisexuals versus 4.1% of heterosexuals reported no health insurance coverage (P < .0001). After adjustments for socioeconomic, health-related behavioral risk, and health care access factors, bisexual females reported poorer general health (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.31-1.36) as well as mental health (OR, 2.43; 95% CI, 2.39-2.46) than their heterosexual peers (P < .0001). Bisexual males were 5.14 times more likely to be told that they had depressive disorders than their heterosexual counterparts (95% CI, 5.05-5.23), whereas bisexual females were 3.23 times more likely for the same outcome (95% CI, 3.18-3.28). All LGB groups reported significantly more inadequate sleep than their heterosexual counterparts (especially lesbians: OR, 2.14; 95% CI, 2.10-2.18). This study indicates that LGB cancer survivors have worse survivorship than their heterosexual peers with heterogeneity in subgroups. Future studies should use larger sample sizes, further investigate disparities, and promote survivorship in LGB populations. It has been observed that lesbian, gay, and bisexual (LGB) cancer survivors may face challenges in cancer survivorship that are not as prevalent in the heterosexual community. This cross-sectional study has found that LGB cancer survivors, especially bisexuals, have overall poorer physical and mental health, are more likely to be told that they have depressive disorders, and have worse sleep quality in comparison with their heterosexual counterparts. These results also differ by sex, and this can provide rationales for future studies and guide interventions to relocate resources to better promote equality.


[Splenectomy--a strictly aseptic intervention?].
To determine the factors causing wound infections after splenectomy, 211 patients undergoing surgery during 1982-1991 were studied in two groups:--Patients with clean-contaminated or contaminated operations with additional splenectomy in the same session;--Patients with elective splenectomy only. While in the first group the rate of disorders of wound healing (DWH) was 31.6%, the second group had a rate of 8.15%. This rate was higher than for other clean operations in our hospital and was as high as for clean-contaminated operations such as cholecystectomy. Among the patients older than 60 years, 38.2% had DWH, as against 8.9% of the patients younger than 60 years. The mean operating time in patients with wound infections was 223 min, while the mean operating time in patients without infections was 125 min. In patients with wound infections the gamma-GT was higher than in patients who had no infection. After these results we have given 2 g ceftriaxon as single-shot prophylaxis before every splenectomy. Since starting this, we have performed 28 splenectomies, and DWH has been observed in only 1 (3.57%). We therefore recommend antibiotic prophylaxis.


Mid-to long-term results of total hip arthroplasty after contralateral lower extremity amputation.
There is limited literature concerning the outcomes and role of THA as a surgical option for amputee patients. The aim of this study is to determine the mid-to long-term survival and complication rates of cementless total hip arthroplasty (THA) in patients with contralateral below knee amputations. A retrospective review of 54 patients with below knee amputation were perfomed who underwent THA for osteoarthritis of the contralateral hip over a 5-year period between 1999 and 2014. Patients were monitored for at least 5 years and assessed with the Harris Hip Score and activities of daily living scale and by evaluating migration or osteolysis around the acetabular cup and femoral stems (amputee group). The amputee group was compared with a control group (non-amputee group) with the same number of patients. Differences in the Harris Hip Score (p = 0.021) and activities of daily living scale (p = 0.043) between the two groups were statistically significant lower in the amputee group at 3 months after surgery. However, no differences were found between the groups from 6 months postoperatively to the last follow-up (Harris Hip Score p = 0.812, activities of daily living scale p = 0.885). Radiologically, any cups or stems showed no signs of migration or osteolysis. In the amputee group, dislocation was found in 1 patient 2 months after arthroplasty (p = 0.315) and long stem revision surgery were performed on two patients due to periprosthetic fracture (p = 0.153). THA performed on the contralateral side of patients with below knee amputation is considered to be an effective treatment with good clinical and radiological results at mid-to long-term follow-up. Level IV, therapeutic study.


Analysis of gene expression of lymphocytes in microgravity.
It has been reported that lymphocyte function decreases under microgravity. Though molecular mechanism of the immunosuppression in microgravity still remains enigmatic, it is suggested that gene expression of lymphocytes may be altered in microgravity. In this study we developed automatic flash-freezing equipment which can be utilized for exposing lymphocytes to microgravity by drop shaft experiments in Japan Microgravity Center (JAMIC). Gene expression profiles were analyzed by using DNA array in ground control lymphocytes and microgravity-exposed lymphocytes.


The problem of the drug-resistant epilepsies.
For the majority of patients with epilepsy, the prognosis for seizure control is very good; however, refractory epilepsy develops in about 20-30% of patients and represents a significant challenge for both clinical management and for research. Physicians treating epilepsy are often asked to predict prognosis and make decisions about commencing and withdrawing treatment. Practice can be guided by epidemiological studies of prognosis. It seems that prognosis depends largely on the aetiology of the seizures and the clinical background of the patient rather than on the seizures themselves or the treatment prescribed. Aetiologies are, however, not the sole determinant of outcome and response to treatment and unknown factors must exit. It is likely that some of these unknown factors are genetically determined but this needs confirmation. The search for these unknown factors that may determine intractability in epilepsy is a very exciting prospect, which may prove to be multifactorial. In some patients, epilepsy may indeed become resistant to treatment whilst in others the propensity for intractability to the drugs currently available may be part and parcel of the condition. Further research is urgently needed to elucidate the full range of mechanisms that lead to drug resistant epilepsy.


Implementation of Advance Care Planning in Oncology: A Review of the Literature.
Advance care planning (ACP) should be initiated early and be readdressed often for patients with cancer. This directive is expressed in the Institute of Medicine's report, "Dying in America," and is a component of several quality metrics, including ASCO's Quality Oncology Practice Initiative and the Centers for Medicare & Medicaid Services Oncology Care Model. Although simple in concept, implementation in practice is challenging. A variety of patient education tools exist in several different forms, including pamphlets, guidebooks, and question prompt lists, with the strongest data supporting the use of video decision aids that depict cardiopulmonary resuscitation. These educational tools should address topics that include anticancer treatment, cardiopulmonary resuscitation, and health care surrogates. Physician prompts in the electronic health record to discuss ACP should be considered. Health care provider training should be offered to meet the needs and comfort level of the practitioners who conduct the intervention. Intervention studies that assessed ACP documentation rates as the primary end point increased documentation from 15% to 30% to 40%. Additional well-conducted randomized studies are needed to understand the intervention characteristics that can further improve the completion and documentation of ACP. Further research is needed to determine if there is a difference in outcome based on which provider conducts ACP as well as how to maximize the benefits of the electronic health record, such as prompts to readdress ACP.


A retinoic acid receptor β2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease.
Hepatic stellate cells (HSCs) are an important cellular target for the development of novel pharmacological therapies to prevent and treat nonalcoholic fatty liver diseases (NAFLD). Using a high fat diet (HFD) model of NAFLD, we sought to determine if synthetic selective agonists for retinoic acid receptor β2 (RARβ2) and RARγ can mitigate HSC activation and HSC relevant signaling pathways during early stages of NAFLD, before the onset of liver injury. We demonstrate that the highly selective RARβ2 agonist, AC261066, can reduce the activation of HSCs, marked by decreased HSC expression of α-smooth muscle actin (α-SMA), in mice with HFD-induced NAFLD. Livers of HFD-fed mice treated with AC261066 exhibited reduced steatosis, oxidative stress, and expression of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFα), interleukin 1β (IL-1β), and monocyte chemotactic protein-1 (MCP-1). Kupffer cell (macrophage) expression of transforming growth factor-β1 (TGF-β1), which plays a critical role in early HSC activation, was markedly reduced in AC261066-treated, HFD-fed mice. In contrast, HFD-fed mice treated with an RARγ agonist (CD1530) showed no decreases in steatosis, HSC activation, or Kupffer cell TGF-β1 levels. In conclusion, our data demonstrate that RARβ2 is an attractive target for development of NAFLD therapies. • Hepatic stellate cells (HSCs) are an important pharmacological target for the prevention of nonalcoholic fatty liver diseases (NAFLD). • Retinoids and retinoic acid receptors (RARs) possess favorable metabolic modulating properties. • We show that an agonist for retinoic acid receptor-β2 (RARβ2), but not RARγ, mitigates HSC activation and NAFLD.


Mechanistic insights into the liquefaction stage of enzyme-mediated biomass deconstruction.
Effective enzyme-mediated viscosity reduction, disaggregation, or "liquefaction," is required to overcome the rheological challenges resulting from the fibrous, hygroscopic nature of lignocellulosic biomass, particularly at the high solids loadings that will be required for an economically viable process. However, the actual mechanisms involved in enzyme-mediated liquefaction, as determined by viscosity or yield stress reduction, have yet to be fully resolved. Particle fragmentation, interparticle interaction, material dilution, and water-retention capacity were compared for their ability to quantify enzyme-mediated liquefaction of model and more realistic pretreated biomass substrates. It was apparent that material dilution and particle fragmentation occurred simultaneously and that both mechanisms contributed to viscosity/yield stress reduction. However, their relative importance was dependent on the nature of the biomass substrate. Interparticle interaction and enzyme-mediated changes to these interactions was shown to have a significant effect on slurry rheology. Liquefaction was shown to result from the combined action of material dilution, particle fragmentation, and alteration of interactions at particle surfaces. However, the observed changes in water retention capacity did not correlate with yield stress reduction. The relative importance of each mechanism was significantly influenced by the nature of the biomass substrate and its physicochemical properties. An ongoing challenge is that mechanisms, such as refining, which enhance enzyme accessibility to the cellulosic component of the substrate, are detrimental to slurry rheology and will likely impede enzyme-mediated liquefaction when high substrate concentrations are used.


Cost-Effectiveness of Total Knee Arthroplasty vs Nonoperative Management in Normal, Overweight, Obese, Severely Obese, Morbidly Obese, and Super-Obese Patients: A Markov Model.
We estimated the cost-effectiveness of performing total knee arthroplasty (TKA) vs nonoperative management (NM) among 6 body mass index (BMI) cohorts. A Markov model was used to compare the cost-utility of TKA and NM in 6 BMI groups (nonobese [BMI 18.5-24.9], overweight [25-29.9], obese [30-34.9], severely obese [35-39.9], morbidly obese [40-49.9], and super-obese [50+] patients) over a 15-year period. Model parameters for transition probability (ie, revision, re-revision, death), utility, and costs were estimated from the literature. Direct medical costs but not indirect societal costs were included in the model. Costs and utilities were discounted 3% annually. The primary outcome was the incremental cost-effectiveness ratio (ICER) of TKA vs NM. One-way and probabilistic sensitivity analyses of the model parameters were performed to determine the robustness of the model. Over the 15-year period, the ICERs for the TKA vs NM for the different BMI categories were nonobese ($3317/quality-adjusted life years [QALYs]), overweight ($2837/QALY), obese ($2947/QALY), severely obese ($3536/QALY), morbidly obese ($5531/QALY), and super-obese ($11,878/QALY). The higher BMI groups tended to have higher incremental QALYs and also higher incremental costs. The probabilistic sensitivity analysis with an ICER threshold of $30,000/QALY showed that TKA would be cost-effective in 100% of simulations of patients with a BMI<50 and 99.16% of super-obese simulations. While performing TKA on super-obese patients is more expensive, the substantial improvements in patient outcomes make it cost-effective. Therefore, withholding TKA care based on a BMI would lead to an unjustified loss of health-care access.


Liver cancer and its prevention.
Liver cancer is one of the leading causes of cancer deaths in Asia and Africa. The epidemiology of liver cancer is distinctive in Japan, where chronic infection with hepatitis C virus (HCV) rather than hepatitis B virus (HBV) plays the major role in the etiology. In this paper, together with a brief review of the descriptive epidemiology of liver cancer and its prevention, Japanese experiences of liver cancer occurrence and some epidemiological studies are described, and Japanese national projects directed against hepatitis and liver cancer are presented. Distinctive time-trends have been observed for liver cancer incidence in Japan. The rates for over 55-59 year olds (both sexes) showed a peak in the birth cohort of 1931-1935, while the rates for less than 50-54 year old females indicate a decreasing trend. The extremely high incidences among birth cohorts around 1931-1935 seems to be related to endemic HCV infection in this generation in Japan. Follow-up studies not only of patients with chronic hepatitis C but also of apparently healthy carriers of HCV showed an increased risk of hepatocellular carcinoma (HCC). Cumulative risk of HCC (40-74 years of age) was estimated as reaching 21.6% (males) and 8.7% (females) among anti-HCV positive voluntary blood donors. Retrospective cohort studies indicated interferon (IFN), with or without ribavirin, to be effective for reducing the risk of HCC among patients with chronic hepatitis C. Periodic examination with ultrasonography and measurement of alpha-fetoprotein has become common practice for early detection of HCCs among patients with chronic hepatitis or liver cirrhosis in Japan. A non-randomized controlled study was conducted to evaluate the effect of periodic examination on mortality, but we failed to show any beneficial effects of screening for liver cancer. In the fiscal year 2002, Japanese National Projects directed against hepatitis and HCC were started, in which blood tests for HCV and HBsAg are offered just once at the age of 40, 45, 50, 55, 60, 65 or 70 for five years. Participants are categorized as either HCV carriers or non-carriers. HCV carriers are further examined by liver disease specialists, seeking indications for IFN therapy. Type C chronic hepatitis patients are recommended to receive IFN therapy with or without ribavirin. This project is expected to become a model of liver cancer control in HCV-endemic countries. Recently however, the US Preventive Service Task Force has recommended against routine screening for HCV infection in asymptomatic adults in the general population who are not at increased risk of infection. This divergence of views is also discussed.


Effects of bifemelane hydrochloride on cerebral circulation and metabolism in patients with aphasia.
The effects of bifemelane hydrochloride on aphasia and on cerebral circulation and metabolism were studied using positron emission tomography (PET) in 10 aphasic patients with cerebrovascular disease. After the first PET scan, bifemelane was administered orally three times in a daily dose of 150 mg. Aphasic features, such as fluency, auditory comprehension, object naming, and repetition, were evaluated by using the Western Aphasia Battery (Japanese edition) before and at least 2 months after bifemelane treatment. Simultaneous with the evaluation of aphasia, the PET scans were performed by using the steady-state method with 15O gases inhalation. All aphasic features, except fluency, improved significantly after bifemelane treatment. Regional cerebral blood flow (rCBF) and the cerebral metabolic rate for oxygen (CMRO2) were increased at every brain region of interest, and the oxygen extraction fraction was decreased. Both rCBF and CMRO2 were significantly increased on the left inferior frontal gyrus, superior temporal gyrus, white matter of the parietal lobe, and insula. These results suggest that bifemelane improves both cerebral oxygen metabolism and cerebral circulation and contributes to the improvement of aphasia caused by cerebrovascular disease.


On the pressure dependence of the thermodynamical scaling exponent γ.
Since its initial discovery more than fifteen years ago, the thermodynamical scaling of the dynamics of supercooled liquids has been used to provide many new important insights in the physics of liquids, particularly on the link between dynamics and intermolecular potential. A question that has long been discussed is whether the scaling exponent γS is a constant or does it depends on pressure. An alternative definition of the scaling parameter, γI = ∂ ln T/∂ ln ρ|X has been presented in the literature, and has been erroneously considered equivalent to γS. Here we offer a simple method to determine the pressure dependence of γI using only the pressure dependence of the glass transition and the equation of state. Using this new method we find that for the six nonassociated liquids investigated, γI always decreases with increasing pressure. Importantly in all cases the value of γI remains always larger than 4. Liquids having γI closer to 4 at low pressure show a smaller change in γI with pressure. We argue that this result has very important consequences for the experimental determination of the functional form of the repulsive part of the potential in liquids. Comparing the pressure and temperature dependence of γS and γI we find, contrary to what has been assumed in the literature to date, that these two parameters are not equivalent and have very different pressure and temperature dependences.


Integrative analysis of cellular autophagy-related genes in steroid-induced osteonecrosis of the femoral head.
This study aimed to identify and evaluate genes associated with cellular autophagy in steroid hormonal femoral head necrosis. Autophagy-related differentially expressed genes (ARDEGs) in steroid-induced osteonecrosis of the femoral head (SONFH) were identified by obtaining the intersection of differentially expressed genes (DEGs) and autophagy-related genes in a SONFH Gene Expression Omnibus dataset. The ARDEGs were screened, and correlations between gene expression and immune cell infiltration were evaluated. Finally, the validation of hub genes was undertaken through quantitative real-time-PCR. A comparison of peripheral blood samples from patients with and without SONFH revealed 189 DEGs. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses showed that the DEGs were related to various biologic processes (e.g., neutrophil activation) and pathways (e.g., hematopoietic cell lineage). The expression levels of these genes were correlated with the infiltration of multiple immune cell types. Among the 189 putative autophagy-related genes associated with SONFH, three genes, RPL6, RPL9, and RPL23, were identified as candidate biomarkers or therapeutic targets based on network analysis and their correlations with immune cell subtypes. The quantitative real-time polymerase chain reaction results confirmed our prediction regarding the mRNA expression of RPL9 and RPS6. In this study, we identified 189 putative autophagy-related genes associated with SONFH, and the prediction of down-regulated genes RPL9 and RPS6 was validated using PCR, thereby expanding our understanding of the contribution of autophagy to SONFH.


The role of thymidine phosphorylase in the induction of early growth response protein-1 and thrombospondin-1 by 5-fluorouracil in human cancer carcinoma cells.
Thymidine phosphorylase (TP) is an enzyme involved in reversible conversion of thymidine to thymine. TP is identical to an angiogenic factor, pletelet-derived endothelial cell growth factor (PD-ECGF) and the expression levels of TP in a variety of malignant tumors were higher than the adjacent non-neoplastic tissues. To investigate the molecular basis for the effect of TP on the metabolic process and the anticancer effect of 5-fluorouracil (5-FU), human gastric carcinoma AZ521 cells and epidermoid carcinoma KB cells were transfected with TP cDNA, and AZ521/TP and KB/TP were cloned. AZ521/TP and KB/TP cells overexpressed TP and were more sensitive to 5-FU than the counterpart parental cells. TPI, a newly synthesized inhibitor for TP (Ki=2.36 x 10(-9) M), decreased the sensitivity to 5-FU of the TP expressing cells but not of the parental cells. 5-Formyl-tetrahydrofolate (leucovorin; LV) stabilized the complex of thymidylate synthase (TS) and 5-fluoro-deoxyuridine-monophosphate (FdUMP), increased the sensitivity to 5-FU of TP expressing AZ521 cells, but not of the parental cells. The levels of FdUMP in TP expressing cells were significantly higher than in parental cells and TPI considerably decreased FdUMP to the level comparable to that in the parental cells. 5-FU increased the expression of early growth response protein-1 (Egr-1) and an angiogenesis inhibitor, thrombospondin-1 (TSP-1), in KB/TP cells but only slightly in KB/CV cells, if any. TPI attenuated the induction of Egr-1 and TSP-1 mRNA by 5-FU, while LV increased the expression of Egr-1 and TSP-1 mRNA in KB/TP cells. These findings demonstrate that the TP has a principal role in the production of FdUMP and the enhanced responses to 5-FU by leucovorin in TP-overexpressing KB and AZ521 cells, and FdUMP but not FUTP is implicated in the induction of Egr-1 and TSP-1 in KB cells.


Human G-CSF produced by adherent cells in the presence of human recombinant GM-CSF.
Adherent cells (AdCs) in blood from normal volunteers produced granulocyte-macrophage (GM) colony-stimulating activity (CSA) in the presence of 10 ng/ml of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in vitro. GM-CSA produced by adherent cells in the presence of GM-CSF reached a plateau level on day 6. Colonies stimulated by adherent cell-conditioned medium (AdC-CM-GM-CSF), which had been harvested after 6 days of incubation of AdCs with rhGM-CSF, were granulocyte predominant. When phagocyte-depleted marrow mononuclear cells (PD-M-MNCs) were cultured with AdC-CM-GM-CSF and anti-rabbit serum against rhGM-CSF, 99% of the colonies on day 7 were exclusively composed of neutrophils. When 2 X 10(4) PD-M-MNCs were cultured in a medium containing AdC-CM-GM-CSF, AdC-CM-GM-CSF + anti-GM-CSF, AdC-CM-GM-CSF + anti-G-CSF, or AdC-CM-GM-CSF + both of the anti-bodies, the PD-M-MNCs formed (mean +/- SD) 100 +/- 2.0%, 64.3 +/- 2.5%, 38.6 +/- 0.4%, and 6.0 +/- 0.4% GM colonies, respectively. Furthermore, northern blot analysis revealed that AdCs incubated with 10 ng/ml of rhGM-CSF for 6 h expressed much more mRNA of G-CSF than those without the CSF. These data indicated that AdCs in blood produce G-CSF in the presence of GM-CSF.


Monoclonal antibody targeting of fibroblast growth factor receptor 1c ameliorates obesity and glucose intolerance via central mechanisms.
We have generated a novel monoclonal antibody targeting human FGFR1c (R1c mAb) that caused profound body weight and body fat loss in diet-induced obese mice due to decreased food intake (with energy expenditure unaltered), in turn improving glucose control. R1c mAb also caused weight loss in leptin-deficient ob/ob mice, leptin receptor-mutant db/db mice, and in mice lacking either the melanocortin 4 receptor or the melanin-concentrating hormone receptor 1. In addition, R1c mAb did not change hypothalamic mRNA expression levels of Agrp, Cart, Pomc, Npy, Crh, Mch, or Orexin, suggesting that R1c mAb could cause food intake inhibition and body weight loss via other mechanisms in the brain. Interestingly, peripherally administered R1c mAb accumulated in the median eminence, adjacent arcuate nucleus and in the circumventricular organs where it activated the early response gene c-Fos. As a plausible mechanism and coinciding with the initiation of food intake suppression, R1c mAb induced hypothalamic expression levels of the cytokines Monocyte chemoattractant protein 1 and 3 and ERK1/2 and p70 S6 kinase 1 activation.


Photochemical Oxidation Specific to Distorted Aromatic Amines Providing ortho-Diketones.
A straightforward visible-light-promoted oxidation of aminohelicenes providing helical ortho-diketones is described. It is shown that the oxidation of amines proceeds via [2 + 2]-cycloaddition reaction with singlet oxygen as an oxidizer and the reaction is specific to distorted aromatic systems. The versatility of the prepared diketones and tetraketones was proven in several heterocycle-forming reactions. The observed adjustment of the physicochemical properties of original molecules is valuable for further development of functional molecules based on helicenes.


Laboratory Activity for the Determination of Nicotine in Electronic Cigarette Liquids using Gas Chromatography-Mass Spectrometry.
In recent years the prevalence and popularity of electronic cigarettes (ECs) has increased noticeably and a large market for their refillable nicotine solutions (e-liquids) has also rapidly increased. These e-liquids contain nicotine, an addictive and potentially dangerous stimulant, but often the actual nicotine content differs significantly from manufacturers' labelling, due in part to lack of regulation for these products. A laboratory activity for undergraduate students was developed to directly test e-liquids for nicotine content using gas chromatography combined with mass spectrometry (GC-MS) as a means for teaching the instrumentation to undergraduate students using an authentic, real-world example. The activity introduces and/or re-emphasizes the theory and operation of GC-MS, standard/sample preparation, calibration curves, internal standards, selected ion monitoring mode of MS operation, and method validation. The laboratory experiment is designed for students enrolled in Quantitative Analysis courses (like Analytical Chemistry or Instrumental Analysis), but portions are also suitable for lower level chemistry courses or even those designed for allied health professionals or non-chemistry majors. Given the current popularity of ECs, this activity can provide the chemistry curriculum with a timely, real-world, and contemporary application in which crucial course content is taught. Students can also benefit from the inherent discussion of ECs, regulations, and related social aspects of smoking and EC vaping - which can serve as a secondary learning outcome.


Expression Profiling and Identification of Novel SNPs in CatSper2 Gene and Their Influence on Sperm Motility Parameters in Bovines.
122 randomly selected Vrindavani cattle were studied to detect polymorphism in four fragments of the CatSper2 gene that were comprised of exon 2, 4, 5, and 6 with flanking regions. Using PCR-SSCP and sequencing analysis, three SNPs (T157C, C273A, and A274C) in the first fragment, one SNP (C30G) in the second fragment, and two SNPs (T86G and T292C) in the fourth fragment were identified. The third fragment did not reveal any polymorphism. The SNPs were used for construction of haplotypes and three haplotypes were found. The least square analysis of variance revealed a significant (P < 0.01) effect of haplotype on all three motility parameters. The haplotype II and III were nonsignificantly different from each other while being significantly (P < 0.01) different from haplotype I. The nonsignificant difference of haplotype II with III can lead to a hypothesis that T>G or C>T SNPs may not play a role in sperm motility. However, when the comparison was made between haplotype I and II, it can be inferred that C>T SNP may have a role in sperm motility, as haplotype II has better motility parameters. Expression profiling of Catper2 gene revealed nonsignificant down regulation of CatSper2 gene in poor motility sperm compared to good motility sperm.


Probiotics intake from proximal or distal gastrointestinal tract: The investigation on intestinal morphology and performance of Japanese quail.
The aim of the present study was to investigate the efficacy of early single-dose probiotics administered from proximal or distal gastrointestinal tract on quails' performance and small intestinal morphology. A total of 120 Japanese quail (Coturnix coturnix japonica) 1-d-old chicks were divided into the following experimental groups before being transferred to the raising room: (i) control (no probiotic administered); (ii) oral group (received probiotics via oesophageal gavage); and (iii) vent lip group (received probiotics directly into vent). Four replicates of 10 chicks per cage were considered for each treatment and birds were raised up to 35 days in the same conditions with ad libitum access to feed and water. A commercial probiotics (Protexin, Somerset, UK) used in this study contained 2 × 109 cfu/g of nine different micro-organisms. On day 35, all birds were weighed and then three birds in every pen were killed via cervical dislocation. Two cm of mid-point of duodenum and ileum were cut for histomorphology assays. Both probiotics-treated groups had higher body weight and body weight gain than control (p < .01). Ileum was longer in probiotics-treated groups than in the control (p < .01). Orally treated birds had the highest duodenum villus height and crypt depth (p < .01). In the cloacally treated quails, ileum villus length was higher than the both other groups, and crypts' depth was deeper than the control (p < .01). The numbers of both types of goblet cells (acidic mucin producer and neutral mucin producer) were higher in the birds receiving probiotics than control birds (p < .01). Although there were no statistical differences in performance values between the different ways of probiotics entrance into gut, some intestinal histomorphometric parameters were improved in ileum of the birds receiving probiotics through distal gut that is cloaca (p < .01).


Selective blockade of apoptosis by in vivo electroporation-mediated gene transfer combined with portal infusion of plasmid DNA attenuates liver cirrhosis.
The purpose of the present study was to determine whether in vivo electroporation could achieve selective blockade of apoptosis in a rat liver cirrhosis model. A dimethylnitrosamine (DMN)-induced rat liver cirrhosis model was used. In vivo electroporation was performed after portal vein infusion of plasmid DNA. pFas-Fc plasmid DNA was used to block the apoptotic pathway. pUC/HGF and pCAGGS/EGFP were used as positive and negative controls, respectively. Liver collagen content was evaluated by hydroxyproline assay two weeks after gene transfer. Terminal deoxynucleotidyltransferase dUTP nick end-labeling was simultaneously performed in the liver to evaluate suppression of apoptosis. Survival analysis was performed using 10 rats that received the sFas gene, 10 that received the HGF gene, and 13 that received the GFP gene. The apoptotic cell index in the DMN-injected liver was significantly lower in rats that received the sFas gene compared with the negative control. The collagen content of the DMN-injected liver was also lower in rats that received the sFas gene compared with the negative control. There was no significant difference in the apoptotic cell index and collagen content of rats that received the sFas and HGF genes. Ten weeks after the initiation of DMN treatment, the survival rates with the sFas, HGF, and GFP genes were 56%, 100%, and 0, respectively. Selective blockade of apoptosis by in vivo electroporation-mediated gene transfer improved the apoptotic cell index, hydroxyproline content, and survival rate. Soluble Fas gene therapy using in vivo electroporation can be a safe and efficient therapy for liver cirrhosis in rats.


Impact of COVID-19 on food behavior and diet in Qatar: A cross-sectional survey on the Omicron variant.
The emergence of the Omicron variant in November 2021 appears to have impacted food-related activities and behaviors and caused disruptions in food supply systems. Accordingly, this article aims to explore the effects of the Omicron variant on consumers' food-related behaviors in Qatar. This research is based on an online survey performed in Qatar in December 2021 and January 2022. The survey consisted of 23 questions arranged into three sections, including both multiple-choice and one-option items. There were 459 valid responses in total. The Omicron variant has altered diets and food shopping in Qatar. Indeed, the findings indicated (i) consumers in Qatar are shopping less often and purchasing more each trip; (ii) an increase in food online shopping; (iii) an increase in the use of online applications to buy ready-made food; and (iv) an increase in the consumption of healthy foods, especially immunity-boosting ones. Furthermore, consumers' awareness and general understanding regarding the virus, its transmission, food safety risks, etc., have evolved. On the one hand, consumers take precautionary measures to protect themselves. On the other hand, they are learning to live with the virus. This research, along with subsequent ones, will provide the foundation for institutional and governmental readiness in the face of potential shocks, crises, and pandemics. The repercussions of the ongoing conflict in Ukraine on food systems throughout the globe (cf. food prices increase) imply that it's a crucial and pressing issue that needs immediate attention.


Measuring functional skills in preschool children at risk for neurodevelopmental disabilities.
Approximately 400,000 preschool children have a major neurodevelopmental disorder impacting on mobility, cognitive-adaptive, or communicative skills. As many as 1 in 3 children live at psychosocial disadvantage because of poverty, parental mental illness or substance misuse, or low parental educational (i.e. less than high school). In the past decade over 500,000 preschool children have survived being born with very low birth weight (1001-1500 g) or extremely low birth weight status (< or =1000 g). Given the scope of these risks and the importance of optimizing outcomes for vulnerable children, this review will highlight advances in functional assessment using adaptive and multiattribute health-related quality of life measures. A framework based on the International Classification of Functioning, (ICF) World Health Organization and the Dynamic Kaleidoscope Model of the Institute of Medicine (IOM) will be described and illustrated with examples of children receiving new biomedical technologies. Assessment scales were chosen for review if they measured adaptive skills or multiattribute health status and had been used in child disability populations. Instruments reviewed include the Infant and Toddler Quality of Life Questionnaire (ITQOL), The Netherlands Office of Prevention Assessment of Preschool Quality of Life (TAPQOL), the Health Status Classification System-PreSchool (HSCS-PS), the Pediatric Evaluation of Disability Inventory (PEDI), the Vineland Adaptive Behavior Scale (VABS), the Warner Inventory of Developmental and Emerging Adaptive and Functional Skills (Warner IDEA-FS), the Scales of Independent Behavior Revised (SIB-R) Early Development Form, the Pediatric Functional Independence Measure (WeeFIM), and the Pediatric Quality of Life Inventory Version 4 (PedsQL 4.0). By measuring functional and adaptive skills and health-related quality of life, we can help devise intervention strategies that optimize developmental independence, family supports, and community participation among children who are at risk for neurodevelopmental disabilities or who have evolving established neurodevelopmental disabilities.


Clinical Correlation Between Vertical Gaze Palsy and Midbrain Volume in Progressive Supranuclear Palsy.
Supranuclear vertical gaze palsies and slowed vertical saccades are characteristic clinic features of progressive supranuclear palsy (PSP). The "hummingbird sign," reflective of midbrain atrophy, is a classic radiographic sign of PSP. Correlation between eye movement abnormalities and radiographic findings in PSP has been reported previously. However, due to the use of clinical criteria not commonly employed in neuro-ophthalmic practice and neuroimaging techniques that are not widely available, it remains unclear whether correlation between midbrain structure and characteristic ocular-motor disturbances can be helpful to neuro-ophthalmologists seeking to adjudicate difficult or unusual diagnostic cases. Patients with a diagnosis of probable PSP according to Movement Disorders Society criteria were studied retrospectively. A neuroradiologist calculated brainstem volumes in enrolled participants and normal controls. Spearman correlations were used to correlate the extent of eye movement limitation as assessed by 2 neuro-ophthalmologists with brainstem volumes. Fourteen participants with PSP and 15 healthy controls with similar age and gender distribution were enrolled and evaluated retrospectively. All 14 participants with PSP had undergone MRIs. Midbrain atrophy significantly correlated with the PSP rating scale (P < 0.001). PSP patients had significantly reduced volumes in the midbrain (P -0.0026), tegmentum (0.0001), tectum (0.0001), and medulla (P = 0.0024) compared with normal controls. Notes documenting quantified ocular motor function were available in 7 of 14 participants with PSP. Midbrain atrophy significantly correlated with in the extent of upward gaze limitation (P = 0.03). The severity of upward gaze limitation correlates with the severity of midbrain atrophy in patients with PSP. Recognition of this correlation may help to adjudicate diagnostic dilemmas and guide further evaluation.


Improved perioperative glycemic control by continuous insulin infusion under supervision of an endocrinologist does not increase costs in patients with diabetes.
To evaluate whether glycemic control can be improved perioperatively by implementing an insulin infusion protocol for patients with diabetes undergoing coronary artery bypass graft (CABG) surgery, without creating an additional financial burden. We also evaluated impact of such a protocol on hospital length of stay (LOS) and development of deep sternal wound infections (DSWI). We developed an insulin infusion glycemic control protocol (IGCP) under supervision and consultation of an endocrinologist. Outcomes of CABG surgery patients with diabetes receiving our IGCP (year 2000) were compared to those of a conventional group of patients with diabetes undergoing CABG prior to the use of the IGCP (year 1999). Cost analysis was performed on data from the hospital's cost accounting database, which included additional costs related to the IGCP. The IGCP group (n=107) showed significantly better glycemic control (mean blood glucose level 183.5 mg/dl +/- SD 53.2 mg/dL; P<0.0001) than the conventional group (n = 81; mean blood glucose level 241.67 mg/dL +/- 75.93 mg/dL). Overall hospital costs were not significantly affected by the intervention. The IGCP group showed a trend toward shorter LOS (IGCP 6.34 days; conventional group 6.58 days) and a reduced rate of DSWI (IGCP 4.63%; conventional group 4.94%). Glycemic control can be improved by implementation of IGCP with no significant additional health care costs. Endocrinologist involvement did not increase costs and improved glycemic management of CABG patients with diabetes.


Antiproliferative and apoptotic effects of a specific antiprostate stem cell single chain antibody on human prostate cancer cells.
Prostate stem cell antigen (PSCA) is a highly glycosylated cell surface protein which is overexpressed in several malignancies including prostate, pancreas, and urinary bladder cancers. Tumor suppression has been reported by anti-PSCA antibody. Small and high affinity single chain antibodies (scFv) have been introduced as effective agents for cancer immunotargeting approaches. In the present study, we used a phage antibody display library of scFv and selected two antibodies against two immunodominant epitopes of PSCA by panning process. The reactivity of the scFvs for the corresponding epitopes was determined by phage ELISA. The binding specificity of antibodies to PSCA-expressing prostate cancer cell line, DU-145, was analyzed by flow cytometry. The antiproliferative and apoptotic induction effects were evaluated by MTT and Annexin-V assays, respectively. Results represented functional scFv C5-II which could bind specifically to DU-145 cells and significantly inhibited the proliferation of these cells (61%) with no effect on PSCA-negative cells. The antibody also induced apoptosis in the PSCA expressing cells. The percentage of the apoptotic cells after 24 hrs of exposure to 500 scFv/cell was 33.80%. These results demonstrate that the functional anti-PSCA scFv C5-II has the potential to be considered as a new agent for targeted therapy of prostate cancer.


Development of education program for physical therapy assistant in Quang Tri province of Vietnam.
[Purpose] The purpose of the present study was to develop an education program for physical therapy assistants in order to provide high quality physical therapy for the province of Quang Tri in Vietnam. [Subjects and Methods] Subjects consisted of 9 professors in Quang Tri medical college and 1 physical therapist in Quang Tri General hospital. The survey research to lecturer for education of physical therapy assistant in Quang Tri medical college was conducted as pre-analysis of demand for the physical therapy assistant curriculum development. The priority rank of expectation and consciousness were measured in curriculum subjects. [Results] Results of educational expectation of the curriculum total educational expectation were presented as minimum 4 to maximum 5. In the result of educational expectation according to background variable, the differences of educational expectation on scores according to the educational experience were significant. Among the consciousness priority of each curriculum subject, the priority rank of basic kinesiology and physical therapy for international medicine & surgery were 9, the highest first rank frequency. [Conclusion] The curriculum for physical therapy assistant was developed to 5 main subjects including a total of 420 hours (120 hours of theory and 300 hours of practice).


Locating Interstitial Hydrides in MH2@Cu14 (M = Cu, Ag) Clusters by Single-Crystal X-ray Diffraction.
Two structures, [Cu15H2(S2CNnBu2)6(C≡CPh)6][CuCl2] (1) and [AgH2Cu14{S2P(OiPr)2}6(C≡CPh)6][PF6] (2), are characterized by X-ray crystallography with high-quality single crystals. The position of interstitial hydrides can be accurately located. In addition, the refinement of the hydrides with anisotropic displacement parameters (ADPs) was successful. The distances between the central atom and copper atoms, as well as the distances within the metal cages surrounding the hydrides, are analyzed and compared with similar MH2@Cu14 (M = Cu, Ag, Pd) compounds. This work provides a thoughtful and accurate assessment of the considerations and challenges associated with anisotropic refinement for H atoms, particularly in X-ray data collection.


What Factors Are Associated with Symptomatic Rotator Cuff Tears: A Meta-analysis.
Rotator cuff tears are common. A previous systematic review reported on factors associated with rotator cuff tears; however, it included relatively few studies and few variables, and in addition, it had considerable heterogeneity. To identify the factors associated with symptomatic rotator cuff tears and to help guide clinicians to potentially modifiable factors, we felt a broader and more inclusive meta-analysis would be useful. In this systematic review and meta-analysis, we asked what (1) demographic, (2) disease, and (3) imaging factors are associated with symptomatic rotator cuff tears? PubMed, Embase, and Web of Science were searched, and the search period were from the inception of each database through February 2021. The keywords included "risk factor," "rotator cuff injury," "rotator cuff tears," and "rotator cuff tendinitis." All comparative studies on symptomatic rotator cuff tears were included. We considered that the diagnosis of rotator cuff tear could be made by any imaging tool (MRI or ultrasound). We considered either partial- or full-thickness tears to be a rotator cuff tear. No language restrictions were applied. Twenty-six articles from 14 countries involving 9809 individuals, consisting of 3164 patients and 6645 controls, were included. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the risk of bias of the included studies, and the highest scores were 9 and 11, respectively. The Newcastle-Ottawa Scale was used for retrospective comparative studies, and the AHRQ was used to evaluate prospective comparative studies. The eight retrospective comparative studies we included were scored from 4 to 9. The quality score of the 18 prospective comparative studies ranged from 6 to 9. Publication bias was explored using the Egger test. Heterogeneity was estimated using the I2 value. If there was no heterogeneity (I2 ≤ 50%), a fixed-effects model was used to determine the overall effect size; if there was heterogeneity (I2 > 50%), a random-effects model was used to merge the effect values. A meta-analysis was performed with RevMan 5.3, and the risk ratio (RR) and weighted mean difference of related factors were calculated. Our meta-analysis identified the following demographic factors associated with an increased risk of rotator cuff tears: older age (mean difference 3.1 [95% CI 1.4 to 4.8]; p < 0.001), greater BMI (mean difference 0.77 [95% CI 0.37 to 1.17]; p < 0.001), smoking (RR 1.32 [95% CI 1.17 to 1.49]; p < 0.001), dominant arm (RR 1.15 [95% CI 1.06 to 1.24]; p < 0.001), greater height (mean difference 0.9 [95% CI 0.4 to 1.4]; p < 0.001), and heavier weight (mean difference 2.24 [95% CI 0.82 to 3.66]; p = 0.002). Regarding disease factors, we found that traumatic events (RR 1.91 [95% CI 1.40 to 2.54]; p < 0.001) and hypertension (RR 1.50 [95% CI 1.32 to 1.70]; p < 0.001) were associated with symptomatic rotator cuff tears. Regarding imaging factors, we found that the following three factors were associated with symptomatic rotator cuff tears: greater acromion index (mean difference 0.11 [95% CI 0.06 to 0.16]; p < 0.001), greater critical shoulder angle (mean difference 1.9 [95% CI 1.5 to 2.3]; p < 0.001), and smaller glenoid version angle (mean difference -1.3 [95% CI -1.9 to -0.8]; p < 0.001). We found no association between the patient's sex or the presence or absence of thyroid disease and the likelihood of a rotator cuff tear being present. This study identified several factors associated with symptomatic rotator cuff tears, including blood glucose, blood pressure, weight, and smoking. Clinicians may seek to modify these factors, possibly in patients with symptomatic rotator cuff tears, but also in symptomatic patients who have not yet been diagnosed with rotator cuff tears because there would be no harm or risk associated with modifying any of the factors we identified. Future research should further study whether addressing these factors can delay the progression and size of rotator cuff tears.Level of Evidence Level III, prognostic study.


[Arrhythmias and heart failure].
Numerous factors contribute to the genesis of arrhythmias and sudden cardiac death in patients with congestive heart failure. Fibrosis of myocardium, ischemia, dilatation of the ventricles and atria, electrolyte imbalance, and neurohumoral factors are examples. Various drugs used in the treatment of congestive heart failure can also precipitate serious arrhythmias. The role of antiarrhythmics, including amiodarone, is still controversial. Judicious antiarrhythmic therapy involves weighing potential benefits of such therapy against risks, such as worsening heart failure or proarrhythmia. In patients with heart failure antiarrhythmic drugs should only be used for symptomatic arrhythmias. Low-dose beta-blockade offers a promising measure for the prevention of sudden cardiac death even in patients with symptomatic congestive heart failure.


The roles of prostaglandin endoperoxides, thromboxane A2 and adenosine diphosphate in collagen-induced aggregation in man and the rat.
The effects of aspirin, carboxyheptylimidazole (CHI) and creatine phosphate/creatine phosphokinase (CP/CPK) on platelet aggregation and thromboxane B2 (TxB2) formation induced by collagen have been examined in vitro. Platelets from two species, man and the rat, have been used. In man, aspirin and CHI abolished TxB2 production but only partially inhibited aggregation. CP/CPK partially inhibited aggregation and TxB2 formation. In the rat, aspirin and CHI abolished TxB2 formation but had no effect on aggregation. CP/CPK completely inhibited aggregation and partially inhibited TxB2 generation. In man, collagen-induced aggregation is largely dependent on ADP and to a lesser extent on arachidonate metabolites whereas, in the rat, ADP alone mediates aggregation induced by this agonist. The results with CP/CPK suggest that TxB2 formation is dependent either on the prior release of platelet ADP or on aggregation itself rather than being responsible for the aggregation response.


Dynamic changes in protein functional linkage networks revealed by integration with gene expression data.
Response of cells to changing environmental conditions is governed by the dynamics of intricate biomolecular interactions. It may be reasonable to assume, proteins being the dominant macromolecules that carry out routine cellular functions, that understanding the dynamics of protein:protein interactions might yield useful insights into the cellular responses. The large-scale protein interaction data sets are, however, unable to capture the changes in the profile of protein:protein interactions. In order to understand how these interactions change dynamically, we have constructed conditional protein linkages for Escherichia coli by integrating functional linkages and gene expression information. As a case study, we have chosen to analyze UV exposure in wild-type and SOS deficient E. coli at 20 minutes post irradiation. The conditional networks exhibit similar topological properties. Although the global topological properties of the networks are similar, many subtle local changes are observed, which are suggestive of the cellular response to the perturbations. Some such changes correspond to differences in the path lengths among the nodes of carbohydrate metabolism correlating with its loss in efficiency in the UV treated cells. Similarly, expression of hubs under unique conditions reflects the importance of these genes. Various centrality measures applied to the networks indicate increased importance for replication, repair, and other stress proteins for the cells under UV treatment, as anticipated. We thus propose a novel approach for studying an organism at the systems level by integrating genome-wide functional linkages and the gene expression data.


Diagnostic dilemmas in atypical postinfectious glomerulonephritis.
This study discusses the differential diagnosis of atypical postinfectious glomerulonephritis (PIGN) which may mimic a great variety of glomerular diseases. These include mild mesangial and/or endocapillary glomerulonephritis (GN) focal segmental glomerulosclerosis (FSGS) with diffuse IgM mesangial deposits, crescentic GN with C3 hump-like deposits, focal mesangiocapillary GN superimposed on endocapillary pattern, membranous GN with diffuse exudative changes, crescentic GN with microabscesses, and postinfectious glomerulonephritis with anti-GBM linear deposits.


Analyses of Entry Mechanisms of Novel Emerging Viruses Using Pseudotype VSV System.
Emerging infectious diseases include newly identified diseases caused by previously unknown organisms or diseases found in new and expanding geographic areas. Viruses capable of causing clinical disease associated with fever and bleeding are referred to as viral hemorrhagic fevers (VHFs). Arenaviruses and Bunyaviruses, both belonging to families classified as VHFs are considered major etiologies of hemorrhagic fevers caused by emerging viruses; having significant clinical and public health impact. Because these viruses are categorized as Biosafety Level (BSL) 3 and 4 pathogens, restricting their use, biological studies including therapeutic drug and vaccine development have been impeded. Due to these restrictions and the difficulties in handling such live viruses, pseudotype viruses bearing envelope proteins of VHF viruses have been developed using vesicular stomatitis virus (VSV) as a surrogate system. Here, we report the successful developments of two pseudotype VSV systems; bearing the envelope proteins of Lujo virus and severe fever with thrombocytopenia syndrome (SFTS) virus, both recently identified viruses of the family Arenaviridae and Bunyaviridae, respectively. My presentation will summarize the characterization of the envelope proteins of Lujo virus including its cellular receptor use and cell entry mechanisms. In addition, I will also present a brief introduction of SFTS reported in Japan and the diagnostic studies in progress using these newly pseudotype VSV system.


Characteristics of four types of patient assaults: six year analysis of the Assaulted Staff Action Program (ASAP).
Although psychiatric patient assaults may include physical and sexual assaults, nonverbal intimidation, and verbal threats, most studies of assaultive psychiatric patients to date have grouped all assaults together in one category. This study explored differences in patient assailant variables and staff victim variables in each of the four categories of patient assault during a six-year period. These differential analyses of assault types yielded at least three important findings: the presence of significant numbers of females as both assailants and victims in several categories of assaults, the importance of psychological fright in staff victims, and the serious psychological disruptions found in staff victims of physical, sexual, and verbal assaults. The findings are discussed and the implications for health care safety and emergency mental health are noted.


Changes in oral functions and muscular behavior due to surgical orthodontic treatment.
The faces of fifteen adult patients who had undergone surgical orthodontic treatment were videotaped frontally and laterally in order to observe their oral circumferential behavior for function and their facial muscle posture at rest. As the ANB angle became 0.9 degrees from -3.5 degrees and the occlusal relationship improved to normal, facial morphology became harmoneous. In general observation, habits of facial muscle tensity at rest was reduced and lip sucking following forward tongue thrusting was decreased after treatment. Pronunciation of previously unclear sounds such as 'Ta' and 'Sa' improved and breath leakage decreased after treatment. The cooperative motions between lips and tongue improved significantly. Although a few subjects still had weak lip tensity and facial muscles, habits of tongue thrusting during swallowing were generally reduced and swallowing motions became more natural. As the movement of tongue tip became smoother, rhythmical chewing improved, and they became capable of chewing on both sides. Good relationships between morphology, oral function, and muscular behavior are very important in stabilization of the normal dentition after surgical orthodontic treatment. Normally maintained forces of balanced occlusion reduce the possibility of relapse.


Improved light extraction efficiency of AlGaN deep-ultraviolet light emitting diodes combining Ag-nanodots/Al reflective electrode with highly transparent p-type layer.
Enhancement of light extraction efficiency (LEE) of AlGaN-based deep-ultraviolet (DUV) light emitting diodes (LEDs) has been attempted by adopting Ag-nanodots/Al reflective electrodes on a highly transparent complex p-type layer. By thinning the p-GaN to several nm, highly DUV transparent p-type layer is achieved, making it meaningful for the application of reflective electrodes composed of Ag-nanodots and Al film to allow most light emitted upward to be reflected back to the sapphire side. By this approach, the maximum light output power and external quantum efficiency of the DUV-LEDs with optimized Ag nanodots/Al electrodes are severally increased by 52% and 58%, respectively, compared to those with traditional Ni/Au electrodes when the current is below 200 mA.


Large variability in clinical judgement and definitions of left bundle branch block to identify candidates for cardiac resynchronisation therapy.
Left bundle branch block (LBBB) morphology is associated with improved outcome of cardiac resynchronisation therapy (CRT) and is an important criterion for patient selection. There are, however, multiple definitions for LBBB. Moreover, applying these definitions seems subjective. We investigated the inter- and intraobserver agreement in the determination of LBBB using available definitions, and clinicians' judgement of LBBB. Observers were provided with 12‑lead ECGs of 100 randomly selected CRT patients. Four observers judged the ECGs based on different LBBB-definitions (ESC, AHA/ACC/HRS, MADIT, and Strauss). Additionally, four implanting cardiologists scored the same 100 ECGs based on their clinical judgement. Observer agreement was summarized through the proportion of agreement (P) and kappa coefficient (k). Relative intra-observer agreement using different LBBB definitions, and within clinical judgement was moderate (range k 0.47-0.74 and k = 0.76 (0.14), respectively). The inter-observer agreement between observers using LBBB definitions as well as between clinical observers was minimal to weak (range k 0.19-0.44 and k = 0.35 (0.20), respectively). The probability of classifying an ECG as LBBB by available definitions varied considerably (range 0.20-0.76). The agreement between different definitions of LBBB ranged from good (P = 0.95 (0.07)) to weak (P = 0.40 (0.22)). Furthermore, correlation between the different LBBB definitions and clinical judgement was poor (range phi 0.30-0.55). Significant variation in the probability of classifying LBBB is present in using different definitions and clinical judgement. Considerable intra- and inter-observer variability adds to this variation. Interdefinition agreement varies significantly and correlation of clinical judgement with LBBB classification by definitions is modest at best.


CLEOPATRA: a phase III evaluation of pertuzumab and trastuzumab for HER2-positive metastatic breast cancer.
Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer have a poor prognosis. Despite proven efficacy with the standard of care, trastuzumab, most patients with HER2-positive metastatic breast cancer (MBC) will eventually progress, requiring further intervention to prolong life. Pertuzumab, a humanized monoclonal antibody, is the first HER2 dimerization inhibitor. It binds to the dimerization site on the HER2 domain and prevents ligand-driven pairing of HER2 with other HER receptors, thus inhibiting tumor cell growth and survival. Combining trastuzumab and pertuzumab therefore provides a more comprehensive blockade of the HER signaling pathways, resulting in greater antitumor efficacy. CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) is an international, randomized, double-blind, placebo-controlled phase III trial that aims to recruit approximately 800 patients from around 250 centers worldwide. Adults with HER2-positive adenocarcinoma of the breast with locally recurrent or metastatic disease will be randomized (1:1) to receive docetaxel, trastuzumab, and pertuzumab or docetaxel, trastuzumab, and placebo. The primary endpoint of the study is progression-free survival (PFS), based on tumor assessments conducted by an independent review facility. Secondary endpoints include PFS evaluated by investigator assessment, overall survival, objective response rate, duration of response, time to symptom progression, and safety. Data will also be collected to identify biomarkers that may correlate with clinical outcomes. The CLEOPATRA study will provide important information about the efficacy and safety of adding pertuzumab to one current standard of care in patients with HER2-positive MBC.


Postoperative Levonorgestrel-Releasing Intrauterine System Insertion After Gonadotropin-Releasing Hormone Agonist Treatment for Preventing Endometriotic Cyst Recurrence: A Prospective Observational Study.
The aim of this study was to evaluate the effectiveness of postoperative levonorgestrel-releasing intrauterine system (LNG-IUS) insertion after gonadotropin-releasing hormone agonist (GnRH-a) treatment for preventing endometriotic cyst recurrence. The LNG-IUS was applied to 28 women who had undergone surgery for endometriosis followed by 6 cycles of GnRH-a treatment. Clinical characteristics, endometriosis recurrence, and adverse effects were analyzed. Student t test was performed for analysis. Before surgery, 20 (71.4%) patients had dysmenorrhea, and the mean pain score (visual analog scale [VAS]) was 4.26. The numbers of women diagnosed with stage III endometriosis and stage IV endometriosis were 15 (53.6%) and 13 (46.4%), respectively, according to the revised American Fertility Society scoring system. The mean cancer antigen 125 levels and VAS scores were significantly lower after treatment than before treatment (11.61 vs 75.66 U/mL, P < .0001 and 0.50 vs 4.26 U/mL, P < .0001, respectively). Of the 28 patients, 13 (46.4%) simultaneously had adenomyosis, and 2 (7.1%) underwent LNG-IUS removal because of unresolved vaginal bleeding and dysmenorrhea. Recurrence was noted in 2 (7.1%) women. Postoperative LNG-IUS insertion after GnRH-a treatment is an effective approach for preventing endometriotic cyst recurrence, especially in women who do not desire to conceive.


Low back pain and biomechanical characteristics of back muscles in firefighters.
Firefighters often experience low back pain (LBP), but their back muscle characteristics are not well studied. This study aimed to 1) compare the biomechanical characteristics of back muscles and self-reported back disabilities in frontline firefighters with and without LBP history, and 2) examine the relationships between back disability and biomechanical measurements. We recruited 42 male firefighters and assessed their perceived pain and disabilities, maximum isometric back extension strength, passive stiffness, and fatigability of the longissimus. 54.8% of the participants experienced LBP within the past year. Those indicating higher pain intensity also had greater disability as indicated by the Oswestry Disability Index. There were no significant differences in strength, stiffness or fatigability of the back muscles between firefighters with and without LBP history. Multiple linear regression analysis revealed no significant relationship between the back disability and any biomechanical or demographic measures, likely due to the high functional abilities of the participants.


Postoperative radiotherapy for squamous cell carcinoma of the head and neck.
This review discusses the role of postoperative radiotherapy (RT) for patients with squamous cell carcinoma of the head and neck. Patients with unfavorable pathologic features have a high-risk of local-regional recurrence and a decreased likelihood of survival after surgery alone. Postoperative RT reduces the risk of local-regional failure and probably improves survival. Patients who are at high risk for recurrence may benefit from more aggressive altered fractionation schedules to decrease the overall time from surgery to the completion of RT. Adjuvant cisplatin-based chemotherapy also appears to improve the probability of cure in high-risk patients.


Transparent and stretchable strain sensors based on metal nanowire microgrids for human motion monitoring.
Optical transparency is increasingly considered as one of the most important characteristics required in advanced stretchable strain sensors for application in body-attachable systems. In this paper, we present an entirely solution-processed fabrication route to highly transparent and stretchable resistive strain sensors based on silver nanowire microgrids (AgNW-MGs). The AgNW-MG strain sensors are readily prepared by patterning the AgNWs on a stretchable substrate into a MG geometry via a mesh-template-assisted contact-transfer printing. The MG has a unique architecture comprising the AgNWs and can be stretched to ε = 35%, with high gauge factors of ∼6.9 for ε = 0%-30% and ∼41.1 for ε = 30%-35%. The sensor also shows a high optical transmittance of 77.1% ± 1.5% (at 550 nm) and stably maintains the remarkable optical performance even at high strains. In addition, the sensor responses are found to be highly reversible with negligible hysteresis and are reliable even under repetitive stretching-releasing cycles (1000 cycles at ε = 10%). The practicality of the AgNW-MG strain sensor is confirmed by successfully monitoring a wide range of human motions in real time after firmly laminating the device onto various body parts.


Ethical enactivism for smart and inclusive STEAM learning design.
Current global challenges of the 21st century promote STEAM (science, technology, engineering, arts and mathematics) education and digitalization as a means for humans to be the central actors in the construction of a sustainable society that favors a sense of worth and global wellbeing. In this scenario, new educational technology tools and immersive learning affordances (possibilities), offer unprecedented potential for the design of smart and dynamic learning systems and contexts that can enhance learning processes across varied audiences and educational settings. However, current STEAM education practice lacks attention to equipping all citizens with the necessary skills to use digital technologies in an ethical, critical and creative way. This gap calls for attention in design processes, principles and practices that are attentive to ethical considerations and values-based approaches. On the other hand, in its formulation STEAM as an educational approach is framed in four fundamental pillars: creativity, inclusion, citizenship and emerging technologies, which also put attention on the inclusion of disadvantaged and underrepresented social groups during STEAM education design. Following an apparent need to explore ethical and inclusive design in STEAM education, and inspired in the 4E cognition framework, ethical enactivism and embodied and ecosomaesthetics experience design, here we propose a theoretical framework grounded on systems thinking for the design of smart and dynamic STEAM learning systems and settings. The framework is aimed at STEAM educational psychologists, educational technologists, learning designers and educational practitioners who wish to address the global challenges of 21st century education by means of creative, innovative and inclusive education design.


Thermoelectric Power Generation and Water Stress in India: A Spatial and Temporal Analysis.
This study aims to reveal the status quo and future trend of thermoelectric water use and water stress in India. We compiled a bottom-up geo-database for all thermal power plants in India and identified the type of cooling technology used. We then estimated thermoelectric water withdrawal and water consumption in India from 2009 to 2018 and projected future trends in thermoelectric water use up to 2027 using the integrated power planning and dispatch model, SWITCH-India. Results show that thermoelectric power generation in India is not a major source of water stress in most basins until 2027. Freshwater withdrawal varied from 14 to 16 billion m3 during the study period, while freshwater consumption increased with growing thermal power generation. The catchment in the middle of the Ganga River basin has the largest freshwater withdrawal and consumption. The volume of water withdrawal accounts for less than 1% of blue water availability in most catchments. It is also likely that a larger proportion of power generation and water withdrawal will occur in catchments that are under lower water stress in the future. Policy interventions should target stressed catchment areas and improve the resilience of thermal power plants to outages due to water stress.