A Randomized Trial of a Low-Fat Diet Intervention on Blood Pressure and Hypertension: Tertiary Analysis of the WHI Dietary Modification Trial.
This post hoc analysis determined if the Women's Health Initiative (WHI) Diet Modification intervention (DM-I) resulted in a significantly different rate of incident hypertension (HTN), as well as longitudinal changes in blood pressure. Participants were 48,835 postmenopausal women aged 50-79 years who were randomly assigned to either the intervention or comparison group. HTN was defined as self-report of treated HTN collected semiannually or blood pressure ≥140/90mm Hg at one of the annual follow-up clinic visits. After a mean follow-up of 8.3 years, and among those who did not have HTN at baseline (n = 31,146), there were 16,174 (51.9%) HTN cases and those assigned to the intervention group had a 4% lower overall risk of developing incident HTN (hazard ratio (HR): 0.96, 95% confidence interval (CI): 0.93-0.99). Although the risk of HTN was lower in the DM-I group in the first few years, the HR became greater than 1 after year 5 (P-trend < 0.01). Similarly, randomization to the DM-I arm resulted in a small but significantly lower average systolic blood pressure (SBP) at 1 year of follow-up (-0.66mm Hg, 0.44-0.89) that increased over the following 8 years (0.16mm Hg/year, 0.11-0.21), such that any early benefit was eliminated by year 5 and a minimal deleterious effect emerged by year 7. Randomization to an intensive behavioral dietary modification program aimed at a lower total fat intake is not associated with sustained reductions in blood pressure or risk of HTN in postmenopausal women. url http://www.clinicaltrials.gov, unique identifier nct00000611.


Childhood obesity: issues of weight bias.
Although the effects of obesity on children's physical health are well documented, the social consequences of obesity are less well described and may not be addressed in intervention programs. Weight bias may take several forms. It may result in teasing and discrimination and may affect employment and educational opportunities. Health care providers may limit care of overweight or obese children. The media promote weight bias in multiple ways. Some parents are biased against their obese children. In an effort to avoid weight bias, new efforts to reduce obesity must be evaluated to determine whether these efforts do, in fact, add to the problem. It is important to understand that the weight bias that obese youth face is just as serious as the physical consequences of excessive weight on the welfare of the child.


Reactive hyperaemia in the hind limbs of rabbits.
Reactive hyperaemia was measured with electromagnetic flowmetry of the terminal aorta in rabbits. The aorta was occluded just above the bifurcation for periods from 10 seconds to 5 minutes. Maximal flow and recovery time of reactive hyperaemia increased significantly with increasing periods of circulatory arrest. Percentual repayment was higher after brief occlusions (10-30 seconds) than after long occlusions (1-5 minutes), when a percentual repayment of about 40% was found. A slight decrease of ascending aortic flow was observed when reactive hyperaemia was induced in the hind limbs. Several mechanisms may play a part in reactive hyperaemia, and the relative importance of the different mechanisms may vary with the length of occlusion.


[Hermeneutics and health: reflections on the thinking of Hans-Georg Gadamer].
This article has as its objective the desire to contribute to nursing practice with the use of Gadamer's hermeneutics. It reflects on the incorporation of the conceptual paradigm of health, care and therapeutic dialogue. In the first section the article discusses the Gadamerian concepts of the work Truth and Method, the hermeneutics philosophy proposed by the philosopher, and it concludes with the articulation of the health concept presented in the work The Hidden Character of Health, which proposes care mediated by therapeutic dialogue and its use by nursing professionals.


A Tumor-Microenvironment-Activated Nanozyme-Mediated Theranostic Nanoreactor for Imaging-Guided Combined Tumor Therapy.
Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme-mediated 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) loaded ABTS@MIL-100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging-guided combined tumor therapy. The as-constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme-mediated "two-step rocket-launching-like" process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H2 O2 level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor-triggered PTT. More importantly, the H2 O2 -activated and acid-enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme-involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.


Dietary melatonin supplementation alters uteroplacental amino acid flux during intrauterine growth restriction in ewes.
Dietary melatonin supplementation during mid- to late-gestation increased umbilical artery blood flow and caused disproportionate fetal growth. This melatonin-induced increase in umbilical artery blood flow may alter nutrient availability to the fetus, which may lead to alterations in fetal size. The objectives of the current experiment were to determine amino acid (AA) and glucose concentrations as well as AA and glucose flux across the uteroplacenta using a mid- to late-gestation model of intrauterine growth restriction supplemented with dietary melatonin as a 2 × 2 factorial design. At day 50 of gestation, 32 ewes were supplemented with 5 mg of melatonin (MEL) or no melatonin (CON) and were allocated to receive 100% (adequate; ADQ) or 60% (restricted; RES) of nutrient requirements. On day 130 of gestation, uterine and umbilical blood flows were determined via Doppler ultrasonography during a non-survival surgery. Blood samples were collected under general anesthesia from the maternal saphenous artery, gravid uterine vein, umbilical artery, and umbilical vein for AA analysis and glucose. Total α-AA concentrations in maternal artery and gravid uterine vein were decreased (P < 0.05) in RES v. ADQ fed ewes. Maternal arterial - venous difference in total α-AA was increased (P ⩽ 0.01) in RES v. ADQ fed ewes, while total uterine α-AA flux was not different (P > 0.40) across all treatment groups. Fetal venous - arterial difference in total α-AA as well as uteroplacental flux of total α-AA were decreased (P < 0.05) in CON-RES v. CON-ADQ, and similar (P > 0.20) in MEL-RES v. CON-ADQ. Maternal concentrations and uterine flux of branched-chain AA (BCAA) were not different across all treatment groups; however, fetal uptake of BCAA was decreased (P < 0.05) in CON-RES v. CON-ADQ, and similar (P > 0.20) in MEL-RES v. CON-ADQ. Uterine uptake of glucose was not different (P ⩾ 0.08) across all treatment groups, while uteroplacental uptake of glucose was increased (P ⩽ 0.05) in RES v. ADQ ewes. In conclusion, maternal nutrient restriction increased maternal arterial - venous difference in total α-AA, while total uterine α-AA flux was unaffected by maternal nutrient restriction. Melatonin supplementation did not impact maternal serum concentrations or uterine flux of glucose or AA; however, melatonin did improve fetal BCAA uptake during maternal nutrient restriction.


The influence of coronary artery disease on quality of life after mechanical valve replacement.
Coronary artery disease (CAD) is known to impact negatively on long-term survival following valve replacement (VR). However, its influence on quality of life (QOL) remains undefined in patients with mechanical VR. A total of 318 consecutive patients undergoing VR with the St. Jude Medical (SJM) mechanical valve were matched for age and gender with 318 patients who had VR (SJM valve) and coronary artery bypass grafting (VR+CABG). The VR group comprised 197 men and 121 women; the VR+CABG group also comprised 197 men and 121 women. The mean age of all patients was 66.0 +/- 8.0 years (range: 40-87 years). The Short Form-36 (SF-36) health survey was administered to all survivors at follow up examination. Operative mortality was comparable between groups (4.7% for VR, 7.5% for VR+CABG; p = 0.186). Hospital complications were also similar, except for reoperation for bleeding (p = 0.049). The mean follow up was 6.0 years for VR patients and 4.7 years for VR+CABG patients. Actuarial survival was significantly better in VR patients than VR+CABG patients (79.4 +/- 2.4% versus 75.0 +/- 2.7% at five years; 58.6 +/- 4.3% versus 47.5 +/- 4.5% at 10 years; p = 0.018). The equality of survival distribution was significantly different (p = 0.008). Multivariate analysis identified CABG as a predictor of late mortality (p = 0.003) but not of late QOL. QOL was similar on the eight health scales and physical health (44.5 +/- 10.3 versus 45.5 +/- 10.7) and mental health (52.4 +/- 9.8 versus 52.5 +/- 10.1) summary components, respectively. Age (p = 0.004), time from surgery to SF-36 administration (p = 0.007) and gender (p = 0.029), but not CABG, were significantly associated with QOL as assessed by the SF-36. CAD is a predictor of late mortality after mechanical VR. However, provided CABG is performed concomitantly with VR, the patient's longterm QOL appears to return to that expected for the general population.


EMIC Waves in the Outer Magnetosphere: Observations of an Off-Equator Source Region.
Electromagnetic ion cyclotron (EMIC) waves at large L shells were observed away from the magnetic equator by the Magnetospheric MultiScale (MMS) mission nearly continuously for over four hours on 28 October 2015. During this event, the wave Poynting vector direction systematically changed from parallel to the magnetic field (toward the equator), to bidirectional, to antiparallel (away from the equator). These changes coincide with the shift in the location of the minimum in the magnetic field in the southern hemisphere from poleward to equatorward of MMS. The local plasma conditions measured with the EMIC waves also suggest that the outer magnetospheric region sampled during this event was generally unstable to EMIC wave growth. Together, these observations indicate that the bidirectionally propagating wave packets were not a result of reflection at high latitudes but that MMS passed through an off-equator EMIC wave source region associated with the local minimum in the magnetic field.


Neurofunctional treatment targeting participation among chronic stroke survivors: a pilot randomised controlled study.
Long-term disabilities are common among stroke survivors and are associated with reduced quality of life (QoL). Research on occupation-based intervention for chronic stroke survivors is sparse. The objective of this study was to examine the effectiveness of neurofunctional treatment (NFT), an occupation-based client-centred treatment approach, for attaining individualised goals in chronic stroke survivors. A pilot randomised control study with a crossover design was employed. The participants were randomly allocated to treatment or control groups, with the intervention replicated for the control group after three months. Twenty three community dwelling stroke survivors, at least one year post-stroke attending a community day centre participated in this study. The 12-week intervention included NFT with individualised occupational goal setting. The treatment methods included task-specific training, environmental or task adaptation, assistive devices, motivation recruitment, and advocacy. Significant differences between the groups were found on occupational performance measures, but not on QoL. These findings were replicated after crossover for the control group. The results support the efficacy of NFT for attaining occupational goals in individuals in the chronic stage after stroke, yet further research is needed to validate these findings in additional treatment settings and over time.


G-Quadruplex Modulation of SP1 Functional Binding Sites at the KIT Proximal Promoter.
The regulation of conformational arrangements of gene promoters is a physiological mechanism that has been associated with the fine control of gene expression. Indeed, it can drive the time and the location for the selective recruitment of proteins of the transcriptional machinery. Here, we address this issue at the KIT proximal promoter where three G-quadruplex forming sites are present (kit1, kit2 and kit*). On this model, we focused on the interplay between G-quadruplex (G4) formation and SP1 recruitment. By site directed mutagenesis, we prepared a library of plasmids containing mutated sequences of the WT KIT promoter that systematically exploited different G4 formation attitudes and SP1 binding properties. Our transfection data showed that the three different G4 sites of the KIT promoter impact on SP1 binding and protein expression at different levels. Notably, kit2 and kit* structural features represent an on-off system for KIT expression through the recruitment of transcription factors. The use of two G4 binders further helps to address kit2-kit* as a reliable target for pharmacological intervention.


Low blood pressure, low mood?
To determine whether a set of physical symptoms is associated with low blood pressure and to investigate the possible role of psychological factors in their occurrence. Analysis of data collected by questionnaire and physical screening from the first phase of the Whitehall II study, a cohort study of an employed population. 23 civil service departments in London. 10,314 male and female London based civil servants aged between 35 and 55. Symptoms of dizziness-giddiness and unexplained tiredness; psychological functioning as measured by the 30 item general health questionnaire in which the response "no more than usual" to an item about disease was scored as indicating chronic illness. Dizziness-giddiness in men and unexplained tiredness in both men and women were significantly related to low systolic blood pressure. There was a highly significant inverse relation between general health questionnaire score and systolic blood pressure for both men and women, which persisted after controlling for potentially confounding variables, including age, body mass index, drug treatment, physical illness, and exercise. This association of low blood pressure with physical symptoms was no longer significant when general health questionnaire score was controlled for. There seems a strong relation between low systolic blood pressure and minor psychological dysfunction. Associated physical symptoms seem to be secondary to the primary disturbance in mental state.


Linear IgA bullous dermatosis with IgA antibodies exclusively directed against the 180- or 230-kDa epidermal antigens.
This study describes the presence in sera from patients with linear IgA bullous dermatosis (LABD) of IgA antibodies specific for 230- or 180-kDa epidermal antigens. Of 11 patients' sera with IgA antibodies reactive with the epidermal antigens obtained from cultured keratinocytes, 6 sera recognized the 230-kDa antigen and co-migrated with the polypeptide recognized by a human monoclonal antibody against the 230-kDa bullous pemphigoid antigen (BPAgl). Five sera recognized the 180-kDa antigen and co-migrated with the polypeptide stained by a polyclonal antibody to the 180-kDa bullous pemphigoid antigen (BPAg2). None of these LABD sera contained IgG antibodies reactive with the basement membrane zone antigens and none labeled a 97-kDa epidermal antigen or a 290-kDa dermal antigen. Immunoaffinity-purified IgA antibodies from the 230 kDa band further reacted with the epidermal side of the skin basement membrane zone. Epitope mapping with rBP55, a fusion protein containing the C-terminal end of BPAg1, suggested that the major antigenic epitopes for LABD and BP antibodies on the 230-kDa antigen are different. Only one serum with IgA antibodies was found to label rBP55, contrasting with nine of ten BP sera reacting with this protein. Our study demonstrates the presence of an exclusive IgA response against the 230- or 180-kDa antigens in a subset of patients with LABD.


Clinical approach to chronic gastrointestinal ischaemia: from 'intestinal angina' to the spectrum of chronic splanchnic disease.
Stenotic disorders of the splanchnic arteries are not rare, and it is generally assumed that symptoms are rare in patients with a single splanchnic stenosis, and even in patients with multiple-vessel stenoses. Currently, only gastric exercise tonometry aids the diagnostic evaluation, as it indicates actual ischaemia. Patients with stenotic disorders without complaints are referred to as having chronic splanchnic disease (CSD) and those with ischaemic complaints as having chronic splanchnic syndrome (CSS). The classical presentation of CSS, including the triad postprandial pain, weight loss and upper abdominal bruit, is also known as 'intestinal angina'. From the experience of our multidisciplinary working team on gastrointestinal ischaemia in 110 patients with stenoses of at least one splanchnic artery, two different clinical patterns were observed. In our series approximately 60% of patients with single-vessel stenoses, including the coeliac artery compression syndrome, have CSS. They have fewer complications, very low mortality, but most can be successfully treated by stenting or surgical treatment. Patients with multivessel splanchnic stenoses have more classical ischaemic complaints. Progression to a bowel infarction was seen in 34%, and mortality was 21%, mostly from bowel or myocardial infarction. Treatment should be tailored based upon perioperative risk assessment and local vascular anatomy. This may consist of autologous arterial bypass of one or two vessels, preferably antegrade. stenting or a combination of both. This differentiation between single- and multivessel splanchnic disease has considerable consequences for optimal work-up and treatment.


Facilitators of and Barriers to Gastric Cancer Screening Among Korean Americans.
Gastric cancer is the most highly prevalent cancer among Korean Americans, occurring at a higher rate than among other Asian Americans and non-Latino Whites. However, little is known about the culturally specific barriers to gastric cancer screening among Korean Americans. The aim of this study was to explore facilitators of and barriers to gastric cancer screening among Korean Americans. In this qualitative focus group study, a convenience sample of 50 Korean Americans aged 21 to 75 years was recruited from the Puget Sound area of Washington with the assistance of Korean churches. Five focus groups of 6 to 8 and 1 focus group of 13 were conducted in a church, a café, and an apartment community center. The focus group discussions lasted approximately 30 minutes to 1 hour. Directed content analysis was used to analyze the data. Facilitators included exposure to Korean media, history and prevalence of gastric problems, perceptions concerning positive aspects of the healthcare system in South Korea, physician recommendations, technology, and church health fair. Barriers included a lack of knowledge, finance/lack of health insurance, fear of test results, perceptions of an inconvenient American healthcare system, a lack of knowledge of American healthcare providers on culturally related health risks, a dislike of medical procedures, and no preventive measures. Sociocultural facilitators and barriers add new knowledge in a field with scarce information available. The study findings lay the groundwork for developing culturally relevant interventions that enhance healthcare providers' awareness while empowering Korean Americans to prevent gastric cancer.


Evidence-based psychosocial treatments for ethnic minority youth.
This article reviews research on evidence-based treatments (EBTs) for ethnic minority youth using criteria from Chambless et al. (1998), Chambless et al. (1996), and Chambless and Hollon (1998). Although no well-established treatments were identified, probably efficacious or possibly efficacious treatments were found for ethnic minority youth with anxiety-related problems, attention-deficit/hyperactivity disorder, depression, conduct problems, substance use problems, trauma-related syndromes, and other clinical problems. In addition, all studies met either Nathan and Gorman's (2002) Type 1 or Type 2 methodological criteria. A brief meta-analysis showed overall treatment effects of medium magnitude (d = .44). Effects were larger when EBTs were compared to no treatment (d = .58) or psychological placebos (d = .51) versus treatment as usual (d = .22). Youth ethnicity (African American, Latino, mixed/other minority), problem type, clinical severity, diagnostic status, and culture-responsive treatment status did not moderate treatment outcome. Most studies had low statistical power and poor representation of less acculturated youth. Few tests of cultural adaptation effects have been conducted in the literature and culturally validated outcome measures are mostly lacking. Recommendations for clinical practice and future research directions are provided.


A carbon budget of a small humic lake: an example of the importance of lakes for organic matter cycling in boreal catchments.
Lakes play an important role in the cycling of organic matter in the boreal landscape, due to the frequently high extent of bacterial respiration and the efficient burial of organic carbon in sediments. Based on a mass balance approach, we calculated a carbon budget for a small humic Swedish lake in the vicinity of a potential final repository for radioactive waste in Sweden, in order to assess its potential impact on the environmental fate of radionuclides associated with organic matter. We found that the lake is a net heterotrophic ecosystem, subsidized by organic carbon inputs from the catchment and from emergent macrophyte production. The largest sink of organic carbon is respiration by aquatic bacteria and subsequent emission of carbon.dioxide to the atmosphere. Although the annual burial of organic carbon in the sediment is a comparatively small sink, it results in the build-up of the largest carbon pool in the lake. Hence, lakes may simultaneously disperse and accumulate organic-associated radionuclides leaking from a final repository.


Aspergillosis of the petrous apex.
We present the case of an immunocompetent man who presented with multiple and progressive cranial nerve palsies. The cause was found to be aspergillosis of the petrous bone, arising as a result of chronic fungal otitis media. Despite treatment with local excision and systemic anti-fungal therapy, he died after suffering a subarachnoid haemorrhage. Diagnosis rests upon prompt radiological imaging and the acquisition of tissue for histological examination and culture but cannot be made without awareness of the condition.


Associations between Mental Health, Lifestyle Factors and Worries about Climate Change in Norwegian Adolescents.
Climate change is a serious global health threat that has an impact on young people's lives and may influence their mental health. Since the global climate strike movement, many adolescents have expressed worries about climate change. Thus, the aim of this study is to examine the prevalence of worries about climate change, and factors associated with worries about climate change, in a representative sample of Norwegian adolescents. Data were retrieved from Ungdata, an annual nationwide online youth survey. Adolescents (n = 128,484) from lower and upper secondary school participated in the study. Data were analysed descriptively and with logistic regression. Most of the adolescents were not worried or a little worried about climate change. Girls, pupils who had at least one parent with higher education and pupils from urban areas were more inclined to worry about the climate. Adolescents who worried about the climate had more symptoms of depression than those who were less worried. While worry about climate change may constitute an additional burden for adolescents experiencing depressive symptoms, such worry can also be seen to reflect climate-friendly values.


Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics.
The transforming growth factor beta (TGF-beta) pathway can play either a tumor-suppressing or a tumor-promoting role in human breast carcinogenesis. In order to determine whether expression of TGF-beta signaling factors varies by age at onset and breast tumor characteristics that have prognostic significance, we undertook a study of 623 women with invasive breast carcinoma enrolled in a population-based case-control study conducted in Poland from 2000 to 2003. TGF-beta signaling factors were analyzed by immunohistochemistry in tumor tissue microarrays. We found that most tumors expressed extracellular-TGF-beta1 (78%), TGF-beta2 (91%), TGF-beta3 (93%), TGF-betaR2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGF-beta1 was expressed in 32% of tumors. Expression of TGF-beta ligands (beta1, beta2, and beta3) was associated with prognostically favorable pathological features including small size, and low grade, and these associations were similar for ER-positive and negative tumors. On the contrary, expression of the receptor TGF-betaR2 was primarily associated with small tumor size among ER-negative tumors, while expression of the transcription factor phospho-SMAD2 was associated with positive nodal status among ER-negative tumors. The greater frequency of expression of phospho-SMAD2 in cancers associated with lymph node metastases is consistent with a pro-progression role for TGF-beta. In addition, expression of extracellular-TGF-beta1 (P = 0.005), TGF-betaR2 (P = 8.2E-11), and phospho-SMAD2 (P = 1.3E-8) was strongly associated with earlier age at onset, independent of ER status. Our data provide evidence that TGF-beta signaling patterns vary by age and pathologic features of prognostic significance including ER expression. These results warrant analysis in studies of clinical outcomes accounting for age, ER status and treatment.


Access to Early Care and Education in Rural Communities: Implications for Children's School Readiness.
This study links county-level early care and education (ECE) program, economic, and demographic data to child-level data from the Early Childhood Longitudinal Study-Kindergarten Cohort of 2010-2011 to examine geographic variation in ECE program participation and provision. We find that public ECE programs, particularly Head Start, occupy a larger role in nonmetropolitan communities than in metropolitan areas. By contrast, children in rural counties are less likely to attend private center-based ECE, and nonprofit childcare program expenditures in rural areas lag. We also find rural-metropolitan differences in school readiness diminish when geographic characteristics are controlled. Results suggest that county-level context and state-level policy features shape children's early experiences, and that public ECE investments are key in narrowing disparities in ECE attendance and in children's outcomes.


Sleep and wake classification with actigraphy and respiratory effort using dynamic warping.
This paper proposes the use of dynamic warping (DW) methods for improving automatic sleep and wake classification using actigraphy and respiratory effort. DW is an algorithm that finds an optimal nonlinear alignment between two series allowing scaling and shifting. It is widely used to quantify (dis)similarity between two series. To compare the respiratory effort between sleep and wake states by means of (dis)similarity, we constructed two novel features based on DW. For a given epoch of a respiratory effort recording, the features search for the optimally aligned epoch within the same recording in time and frequency domain. This is expected to yield a high (or low) similarity score when this epoch is sleep (or wake). Since the comparison occurs throughout the entire-night recording of a subject, it may reduce the effects of within- and between-subject variations of the respiratory effort, and thus help discriminate between sleep and wake states. The DW-based features were evaluated using a linear discriminant classifier on a dataset of 15 healthy subjects. Results show that the DW-based features can provide a Cohen's Kappa coefficient of agreement κ = 0.59 which is significantly higher than the existing respiratory-based features and is comparable to actigraphy. After combining the actigraphy and the DW-based features, the classifier achieved a κ of 0.66 and an overall accuracy of 95.7%, outperforming an earlier actigraphy- and respiratory-based feature set ( κ = 0.62). The results are also comparable with those obtained using an actigraphy- and cardiorespiratory-based feature set but have the important advantage that they do not require an ECG signal to be recorded.


Ipsilateral femoral fracture non-union and delayed union treated by hybrid plate nail fixation and vascularized fibula bone grafting: a case report.
Non-union is a well recognized complication of femoral neck fractures. The decision whether to attempt fracture fixation or to resort to hip replacement is particularly difficult in patients in the borderline age group in whom complex attempts at gaining union may fail and later present a difficult revision. On the other hand the patient may be young enough that arthroplasty best be avoided . Besides, presence of ipsilateral femoral shaft fracture with delayed union in addition to the femoral neck non-union will pose major problems at operation. We share our experience in treating a femoral neck fracture non-union with ipsilateral femoral shaft delayed union in the shaft and in the distal femur in a fifty years old patient. The fracture was treated with an angle blade plate and supracondylar nail supplemented with a free vascularised fibular bone grafting and autologous cancellous graft. There was radiological union at fourth month. At sixth months, the patient was free of pain and able to walk without support. Thus, we would like to suggest that vascularised fibula bone grafting with supracondylar nailing is a viable option for this pattern of fracture. Vascularized fibular bone graft, neck of femur, femoral shaft fracture, non-union.


Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial.
Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: - 23.7%; 80% confidence interval [CI] - 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) μg/mL, with 80.6% (n = 58/72) subjects achieving concentrations > 1.7 μg/mL, a level associated with improved outcome in animal models. Treatment-emergent adverse event incidence was similar between groups. The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov ( NCT02696902 ) on 11th February 2016 and on EudraCT ( 2015-001706-34 ) on 7th March 2016.


Impact of Concomitant Mitral Valve Surgery With LVAD Placement: Systematic Review and Meta-Analysis.
The aim of this systematic review and meta-analysis was to evaluate the outcomes of concomitant mitral valve surgery for significant preexisting mitral regurgitation (MR) in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) implantation. Electronic search was performed to identify all studies in the English literature examining concurrent mitral valve surgery in patients with CF-LVAD implantation. Identified articles were systematically assessed for inclusion and exclusion criteria. Of 2319 studies identified, 8 studies were included. Among 445 patients with moderate to severe or severe MR, 113 (25.4%) patients received concurrent mitral valvular intervention during CF-LVAD implantation. There were no significant differences in cardiopulmonary bypass time (MR Surgery 154 min vs. no MR Surgery 119 min, P = 0.64) or hospital length of stay (MR Surgery 21 days vs. no MR Surgery 18 days, P = 0.93). On follow-up, there were no significant differences in freedom from greater than moderate MR (MR Surgery 100% vs. no MR Surgery 74%, P = 0.12) or left ventricular end-diastolic diameter (MR Surgery: 60 mm vs. no MR Surgery 65 mm, P = 0.51). Survival was comparable at 6-months (MR Surgery 77% vs. no MR Surgery 81%, P = 0.75), 1-year (MR Surgery 72% vs. no MR Surgery 80%, P = 0.36), and 2-years of follow-up (MR Surgery 65% vs. no MR Surgery 70%, P = 0.56). The results of our systematic review and meta-analysis of 8 studies consisting of 445 patients demonstrates that the addition of mitral valve intervention to CF-LVAD implantation appears to be safe with comparable survival to those undergoing CF-LVAD implantation alone. Large prospective randomized clinical trials are needed to elucidate whether concomitant mitral valve intervention during CF-LVAD implantation in patients with severe MR is necessary.


Tanshinone IIA acts via p38 MAPK to induce apoptosis and the down-regulation of ERCC1 and lung-resistance protein in cisplatin-resistant ovarian cancer cells.
Tanshinone IIA is known to induce apoptosis in several types of cancer cells. However, little is known about its activity in chemoresistant cells. The aim of this study was to investigate the anticancer properties of tanshinone IIA in cisplatin-resistant human ovarian cancer COC1/DDP cells in vitro. We used a variety of methods to measure cell viability, the resistance index (RI) of cisplatin, cellular apoptosis, p38 mitogen-activated protein kinase (MAPK) expression and phosphorylation, and the mRNA expression of several genes implicated in drug resistance including survivin, Caspase-3, excision repair cross-complementing gene 1 (ERCC1), multidrug resistance (MDR), lung resistance protein (LRP) and glutathione-S-transferase-π (GST-π). We found that tanshinone IIA time- and dose-dependently inhibited the proliferation of COC1/DDP cells and caused significant apoptosis. Western blotting revealed that tanshinone IIA also increased phospho-p38 MAPK in a time- and dose-dependent manner. After treatment by tanshinone IIA for 48 h, the RI of cisplatin and the mRNA expression of survivin, ERCC1 and LRP were all significantly decreased. Furthermore, blockade of p38 signal transduction decreased apoptotic cell rates and dramatically elevated the mRNA expression of the survivin, ERCC1 and LRP genes. We therefore conclude that tanshinone IIA induces apoptosis and reduces cisplatin resistance in COC1/DDP cells and thus causes significant growth inhibitory effects. This mechanism appears to involve p38-mediated downregulation of survivin, ERCC1 and LRP mRNA expression.


Low-voltage electrostatic field enhances the frozen force of -12 ℃ to suppress oxidative denaturation of the lamb protein during the subsequent frozen storage process after finishing initial freezing.
The effect of low-voltage electrostatic field (LVEF) assisted -9 °C (LVEF-9) and -12 °C (LVEF-12) frozen, non-LVEF-assisted -9 °C (NLVEF-9) and -12 °C (NLVEF-12) frozen, and conventional frozen (CF-18, -18 °C) storage on the muscle microstructure and the oxidative denaturation of the lamb protein during the subsequent frozen storage process after finishing initial freezing was investigated. Compared with NLVEF-9, LVEF-9, and NLVEF-12, LVEF-12 maintained the better integrity of muscle microstructure, demonstrated by smaller holes, more complete Z-line and M-line, and no significant difference with CF-18 (P > 0.05). Furthermore, LVEF-12 effectively inhibited protein oxidative denaturation as shown by the lower carbonyl content, surface hydrophobicity, and higher total/active sulfhydryl groups and Ca2+-ATPase activity. Moreover, LVEF-12 effectively maintained the integrity of the secondary and tertiary structure of proteins, reduced cross-linking aggregation of proteins, and sustained better functional properties, as shown by higher α-helix content, fluorescence intensity, protein solubility, and lower R-value, disulfide bonds.


On Negative Heritability and Negative Estimates of Heritability.
We consider the problem of interpreting negative maximum likelihood estimates of heritability that sometimes arise from popular statistical models of additive genetic variation. These may result from random noise acting on estimates of genuinely positive heritability, but we argue that they may also arise from misspecification of the standard additive mechanism that is supposed to justify the statistical procedure. Researchers should be open to the possibility that negative heritability estimates could reflect a real physical feature of the biological process from which the data were sampled.


Effects of concurrent use of rh-IFN-gamma and curcumin on the anti-proliferative capacity of HL-60 cells.
To understand the effect of rh-IFN-gamma on the ability of curcumin to kill HL-60 cells in vitro, the myeloid leukemic cell line HL-60 was studied by using cell culture. BrdU incorporation rate was examined by SABC, DNA content was determined by flow cytometry and apoptotic cell percentage was determined by TUNEL method. The results showed that curcumin inhibited proliferation of leukemic cells in a dose-dependent manner. When HL-60 cells were treated with 25 mumol curcumin for 24 h, the proliferative inhibitory rate was 43.75 +/- 2.00%. This effect could be enhanced obviously by IFN-gamma, the combined proliferative inhibitory rate increased to over 80%. The 5-BrdU incorporation rate and the distribution of DNA content indicated that curcumin could arrest cells in the G1/G0 and G2/M phase of cell cycle. At the same time, the sub-G1 peak (apoptotic peak) appeared. After IFN-gamma combined with curcumin, DNA synthesis rate decreased further. It showed a significant difference when compared with single drug group (P < 0.05). Meanwhile, sub-G1 peak also increased. The percentage of TUNEL positive cells was aslo increased. It is concluded that IFN-gamma can enhance the antiproliferative ability of curcumin against HL-60 cells.


The pharmacokinetics and pharmacodynamics of a new sustained-release leuprolide acetate depot compared to market references.
The aim of this study was to compare the efficacy of Lutrate 3.75 and 7.5 mg depot to marketed references Lucrin 3.75 mg and Procrin 7.5 mg depot. 20 healthy male volunteers were randomly assigned to receive 1 of 4 active single dose treatments in this double-blind, parallel-group pilot study. Leuprolide acetate and testosterone levels were quantified by radioimmunoassays. The pharmacokinetic profile of leuprolide could be well-described by a 4-step release curve. Leuprolide levels were detectable 14 days longer after injection of the test formulations as compared to the reference products. The total AUC observed with 3.75 and 7.5 mg of the test product were approximately 1.5- and 2.2-fold higher, compared to the reference products, respectively. After the expected testosterone "flare-up" effect, castration was achieved in 4 of 4 subjects with the test formulations, 4 of 5 subjects with Procrin and 2 of 5 subjects with Lucrin. On average, castration lasted more than 1 month with both test formulations compared to 2 weeks with the reference products. Sustained release of leuprolide from this new depot formulation suppressed testosterone levels at least as effectively and for a longer period of time than the reference products.


Occupational asthma.
Substantial epidemiologic and clinical evidence indicates that agents inhaled at work can induce asthma. In industrialized countries, occupational factors have been implicated in 9 to 15% of all cases of adult asthma. Work-related asthma includes (1) immunologic occupational asthma (OA), characterized by a latency period before the onset of symptoms; (2) nonimmunologic OA, which occurs after single or multiple exposures to high concentrations of irritant materials; (3) work-aggravated asthma, which is preexisting or concurrent asthma exacerbated by workplace exposures; and (4) variant syndromes. Assessment of the work environment has improved, making it possible to measure concentrations of several high- and low-molecular-weight agents in the workplace. The identification of host factors, polymorphisms, and candidate genes associated with OA is in progress and may improve our understanding of mechanisms involved in OA. A reliable diagnosis of OA should be confirmed by objective testing early after its onset. Removal of the worker from exposure to the causal agent and treatment with inhaled glucocorticoids lead to a better outcome. Finally, strategies for preventing OA should be implemented and their cost-effectiveness examined.


Inhibition of superoxide anion-mediated impairment of endothelium by treatment with luteolin and apigenin in rat mesenteric artery.
This study was designed (i) to test the hypothesis that the endothelium-derived hyperpolarizing factor (EDHF) component of ACh-induced vasorelaxation and hyperpolarization of smooth muscle cells (SMCs) are impaired following exposure to superoxide anion, and (ii) to further investigate whether luteolin and apigenin induce vasoprotection at the vasoactive concentrations in rat mesenteric artery. Rat mesenteric arterial rings were isolated for isometric force recording and electrophysiological studies. Perfusion pressure of mesenteric arterial bed was measured and visualization of superoxide production was detected with fluorescent dye. 300 microM pyrogallol significantly decreased the relaxation and hyperpolarization to ACh. Luteolin and apigenin both induced vasoprotection against loss of the EDHF component of ACh-induced relaxation and attenuated the impairment of hyperpolarization to ACh. Oxidative fluorescent microtopography showed that either luteolin or apigenin significantly reduced the superoxide levels. The results suggest that superoxide anion impairs ACh-induced relaxation and hyperpolarization of SMC in resistance arteries through the impairment of EDHF mediated responses. Luteolin and apigenin protect resistance arteries from injury, implying that they may be effective in therapy for vascular diseases associated with oxidative stress.


Behavioural modification framework to address wastage in household electricity consumption.
Household electricity wastage poses a sustainability issue. Ergonomic interventions that prevent wastage through technological innovations are expensive and complex, making consumers unwilling to adopt them. The study aimed to investigate the motivations and impediments in avoiding electricity wastage. Thirteen Repertory Grid interviews were conducted on household electricity users relating to the behaviour of those living with them. The key motivational themes found were altruistic and egoistic reasons while the impediments were perceived behavioural control, hedonism and self-efficacy. Based on the research findings, a behavioural modification framework was developed to encourage consumers to adopt a higher level of responsible electricity practice through the following suggested interventions - (1) reframing sustainability from 'future-for-others' to 'present-for-us', (2) clarifying responsible consumption and (3) performance feedback. The research identified the key motivations and impediments of being a responsible household electricity user and provided a framework to encourage a higher responsibility level. Practitioner Summary: Household electricity wastage poses sustainability issue: excess CO2 & high costs. We developed a mindset changing behavioural modification framework. We investigated HFE issues: motivations & impediments of avoiding the wastage, i.e. altruistic, egoistic, behavioural control, hedonism & self-efficacy. The framework provides governments insights into strategies to address the wastage.


Gender differences in the polysomnographic features of obstructive sleep apnea.
We examined the influence of gender on the polysomnographic features of obstructive sleep apnea (OSA) in a retrospective study of 830 patients with OSA diagnosed by overnight polysomnography (PSG). The severity of OSA was determined from the apnea- hypopnea index (AHI) for total sleep time (AHI(TST)), and was classified as mild (5 to 25 events/h), moderate (26 to 50 events/h), and severe (> 50/events/h). Differences in OSA during different stages of sleep were assessed by comparing the AHI during non-rapid eye movement (NREM) (AHI(NREM)) and rapid eye movement (REM) (AHI(REM)) sleep and calculating the "REM difference" (AHI(REM) - AHI(NREM)). Additionally, each overnight polysomnographic study was classified as showing one of three mutually exclusive types of OSA: (1) mild OSA, which occurred predominantly during REM sleep (REM OSA); (2) OSA of any severity, which occurred predominantly in the supine position (S OSA); or (3) OSA without a predominance in a single sleep stage or body position (A OSA). The mean AHI(TST) for men was significantly higher than that for women (31.8 +/- 1.0 versus 20.2 +/- 1.5 events/h, p < 0. 001). The male-to-female ratio was 3.2:1 for all OSA patients, and increased from 2.2:1 for patients with mild OSA to 7.9:1 for those with severe OSA. Women had a lower AHI(NREM) than did men (14.6 +/- 1.6 versus 29.6 +/- 1.1 events/h, p < 0.001), but had a similar AHI(REM) (42.7 +/- 1.6 versus 39.9 +/- 1.2 events/h). Women had a significantly higher REM difference than did men (28.1 +/- 1.5 versus 10.3 +/- 1.1 events/h, p < 0.01). REM OSA occurred in 62% of women and 24% of men with OSA. S OSA occurred almost exclusively in men. We conclude that: (1) OSA is less severe in women because of milder OSA during NREM sleep; (2) women have a greater clustering of respiratory events during REM sleep than do men; (3) REM OSA is disproportionately more common in women than in men; and (4) S OSA is disproportionately more common in men than in women. These findings may reflect differences between the sexes in upper airway function during sleep in patients with OSA.


cis-Diamminedichloroplatinum(II) (DDP)-induced crosslinking and crosslink removal in L1210 cells in vitro after theophylline co-treatment.
The present study investigated the mechanism by which theophylline decreases cis-diamminedichloroplatinum(II) (DDP)-induced DNA crosslinking in L1210 cells. Alkaline elution of DNA from L1210 cells treated with DDP in the presence and absence of 1 mM theophylline showed that theophylline decreased interstrand crosslinking by 20%. DNA-protein crosslinking (PXL) immediately following platinum removal (used as a measure of active drug delivered to the cell nucleus) was not altered by theophylline nor were the kinetics of either DNA interstrand (ISC) or DNA-protein crosslink formation after DDP treatment changed by the presence of theophylline. Peak protein crosslinking occurred 6 hr and peak interstrand crosslinking occurred 12 hr after DDP removal. We measured crosslink removal by using thiourea to block the conversion of platinum monoadducts to crosslinks. DNA-protein crosslinks were removed more rapidly in the presence of theophylline. There was no change in interstrand crosslink removal rate when theophylline was present. We conclude that the addition of theophylline to DDP treatment results in decreased amounts of DNA interstrand crosslinking most likely by increasing the removal of DPP-DNA monoadducts. This latter process may be reflected by the increased removal rates for DNA-protein crosslinks.


Source selection for real-time user intent recognition toward volitional control of artificial legs.
Various types of data sources have been used to recognize user intent for volitional control of powered artificial legs. However, there is still a debate on what exact data sources are necessary for accurately and responsively recognizing the user's intended tasks. Motivated by this widely interested question, in this study we aimed to 1) investigate the usefulness of different data sources commonly suggested for user intent recognition and 2) determine an informative set of data sources for volitional control of prosthetic legs. The studied data sources included eight surface electromyography (EMG) signals from the residual thigh muscles of transfemoral (TF) amputees, ground reaction forces/moments from a prosthetic pylon, and kinematic measurements from the residual thigh and prosthetic knee. We then ranked and included data sources based on the usefulness for user intent recognition and selected a reduced number of data sources that ensured accurate recognition of the user's intended task by using three source selection algorithms. The results showed that EMG signals and ground reaction forces/moments were more informative than prosthesis kinematics. Nine to eleven of all the initial data sources were sufficient to maintain 95% accuracy for recognizing the studied seven tasks without missing additional task transitions in real time. The selected data sources produced consistent system performance across two experimental days for four recruited TF amputee subjects, indicating the potential robustness of the selected data sources. Finally, based on the study results, we suggested a protocol for determining the informative data sources and sensor configurations for future development of volitional control of powered artificial legs.


Emergence of hospital- and community-associated panton-valentine leukocidin-positive methicillin-resistant Staphylococcus aureus genotype ST772-MRSA-V in Ireland and detailed investigation of an ST772-MRSA-V cluster in a neonatal intensive care unit.
Sequence type 22 (ST22) methicillin-resistant Staphylococcus aureus (MRSA) harboring staphylococcal cassette chromosome mec (SCCmec) IV (ST22-MRSA-IV) has predominated in Irish hospitals since the late 1990s. Six distinct clones of community-associated MRSA (CA-MRSA) have also been identified in Ireland. A new strain of CA-MRSA, ST772-MRSA-V, has recently emerged and become widespread in India and has spread into hospitals. In the present study, highly similar MRSA isolates were recovered from seven colonized neonates in a neonatal intensive care unit (NICU) in a maternity hospital in Ireland during 2010 and 2011, two colonized NICU staff, one of their colonized children, and a NICU environmental site. The isolates exhibited multiantibiotic resistance, spa type t657, and were assigned to ST772-MRSA-V by DNA microarray profiling. All isolates encoded resistance to macrolides [msr(A) and mpb(BM)] and aminoglycosides (aacA-aphD and aphA3) and harbored the Panton-Valentine leukocidin toxin genes (lukF-PV and lukS-PV), enterotoxin genes (sea, sec, sel, and egc), and one of the immune evasion complex genes (scn). One of the NICU staff colonized by ST772-MRSA-V was identified as the probable index case, based on recent travel to India. Seven additional hospital and CA-ST772-MRSA-V isolates recovered from skin and soft tissue infections in Ireland between 2009 and 2011 exhibiting highly similar phenotypic and genotypic characteristics to the NICU isolates were also identified. The clinical details of four of these patients revealed connections with India through ethnic background or travel. Our study indicates that hospital-acquired and CA-ST772-MRSA-V is currently emerging in Ireland and may have been imported from India on several occasions.


Entry of monocytes into the brain after injection of Corynebacterium parvum.
The receptiveness of the brain to monocyte infiltration was studied in rats that had been injected intracerebrally with Corynebacterium parvum. At 0-17 days after intracerebral injection and 18 h after intravenous injection of diI-labeled isogenous mononuclear cells, host rats were sacrificed and cells from the vicinity of the injection site and from the contralateral cerebral hemisphere were dissociated and analyzed by flow cytometry. In rats sacrificed 4-11 days postinjection of C. parvum, diI-labeled mononuclear cells were detected in cell preparations from the hemisphere ipsilateral and, to a lesser extent, contralateral to the injection site. No extravasation of cells from the blood to the brain was detected in rats injected intracerebrally with saline. By immunohistochemistry, many macrophages were detected in the hemisphere ipsilateral to injection of C. parvum. In additional experiments, the dissociated CNS cell population was labeled with OX-42 antibodies to the type 3 complement receptor, which is present on monocytes but not lymphocytes. Some cells in the brain were labeled with both diI and OX-42 and therefore were identified as monocytes that had entered the brain from the blood. In conclusion, monocytes can home to both sides of the brain after unilateral injection of a strong inflammatory agent but monocyte infiltration into the brain is delayed in comparison to monocyte inflammatory responses that have been reported in nonneural tissues.


Cardiac risk assessment of asymptomatic patients by stress echocardiography before infrarenal aortic aneurysm surgery.
Aggressive cardiac assessment before aortic abdominal aneurysm (AAA) surgery is indicated for patients with symptomatic coronary artery disease (CAD). Assessment of intermediate and moderate risk patients is still under debate. The purpose of the study was to prospectively evaluate the effectiveness of stress echocardiography (SE) in the detection of CAD in patients undergoing AAA surgery who have no symptoms and/or signs of CAD, but who have risk factors for it. Patients with 1 or more risk factors for CAD underwent SE. All patients with positive SE underwent coronary arteriography, and, when indicated, treatment. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for SE by comparing results to coronary arteriography. Moreover, major perioperative cardiac events were recorded. Ninety-one patients with AAA and risk factors for CAD were studied. SE was positive in 9 cases, including 7 presenting critical CAD on the basis of coronary arteriography. One major cardiac event (1.1%), a nonfatal myocardial infarction, occurred in 1 patient with positive SE and non-critical, single-vessel CAD. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SE proved to be 100%, 98%, 78%, 100%, and 92%, respectively. Positive SE should be considered a valid method for testing high-risk patients for CAD. The low rate of major cardiac events in this series suggests that cardiac assessment by SE and selective coronary arteriography prior to AAA surgery is effective in asymptomatic patients with one or more risk factors.


Folding and Stabilization of Native-Sequence-Reversed Proteins.
Though the problem of sequence-reversed protein folding is largely unexplored, one might speculate that reversed native protein sequences should be significantly more foldable than purely random heteropolymer sequences. In this article, we investigate how the reverse-sequences of native proteins might fold by examining a series of small proteins of increasing structural complexity (α-helix, β-hairpin, α-helix bundle, and α/β-protein). Employing a tandem protein structure prediction algorithmic and molecular dynamics simulation approach, we find that the ability of reverse sequences to adopt native-like folds is strongly influenced by protein size and the flexibility of the native hydrophobic core. For β-hairpins with reverse-sequences that fail to fold, we employ a simple mutational strategy for guiding stable hairpin formation that involves the insertion of amino acids into the β-turn region. This systematic look at reverse sequence duality sheds new light on the problem of protein sequence-structure mapping and may serve to inspire new protein design and protein structure prediction protocols.


Vitreous Seeds in Retinoblastoma: Clinicopathologic Classification and Correlation.
A recent classification scheme for retinoblastoma vitreous seeds has shown promise in predicting treatment response. For the first time, we correlate this clinical classification scheme with its histopathologic features. Retrospective review. Enucleated eyes received at the pathology department of the Retinoblastoma Center of Houston from 2010 to 2015. Macroscopic photographs of the enucleated eyes of patients with retinoblastoma were analyzed to select those with vitreous seeds. Cases with adequate material for clinicopathologic correlation were selected for further analysis, and clinical photographs were reviewed. Routine histopathologic slides were reviewed and compared with the clinical and macroscopic photographs. Seeds were classified as type 1 ("dust"), type 2 ("sphere"), or type 3 ("cloud"). To confirm the presence of macrophages, CD68 immunohistochemical staining was used. Synaptophysin was used to stain retinoblastoma cells. To correlate clinical vitreous seed type with histopathologic features. A total of 14 eyes with adequate amounts of tumor seeds along with clinical and macroscopic photographic correlation were selected from a total of 138 eyes reviewed. Type 1 seeds consisted of individual viable tumor cells and scattered macrophages. Type 2 seeds consisted of 2 submorphologies: spheres with viable cells throughout and spheres with an outer rim of viable cells but necrotic cells centrally. Type 3 seeds were composed of more than 90% necrotic material admixed with few macrophages and viable cells at their outer rim. Untreated (8/14) and previously treated (6/14) eyes showed similar histopathologic features for each type of seeds. Treated eyes had more type 1 and 3 seeds. We provide the first histopathologic correlation of the clinical classification scheme for vitreous seeds in retinoblastoma. "Dust" is formed by scattered single cells alternating with macrophages. "Spheres" with translucent centers contain multiple layers of viable tumor cells that shed single cells and may be more clinically aggressive. "Cloud" seeds are mostly composed of necrotic material, explaining their lack of therapeutic response. Pretreated eyes showed tumor seeds morphologically similar to untreated eyes. Knowledge of the underlying histopathology of vitreous seed types is a fundamental component of classification and may aid in understanding clinical response to treatment.


[Metabolic syndrome in children].
Currently, the metabolic syndrome (MS)--one of the pressing problems of Pediatrics, which is caused by variety of clinical manifestations and the lack of uniform criteria for diagnosis. MS is a complex of metabolic disorders, which is based on dyslipidemia, insulin resistance, compensatory hyperinsulinemia. In the pediatric preclinical and clinical manifestations of MS are often hidden under the guise of various diseases associated with it, which greatly complicates the diagnosis of MS in children. In connection with the foregoing the purpose of this work was to show a clinical example of the difficulties in identifying symptoms of MS in children to optimize its diagnostic tactics.


[Memory disorders in senile dementia].
Being induced by a certain external cause, coherent ideas of the events gone by may occur in the consciousness of senile dementia patients. These observations suggest that memory stores in senile dementia remain outside the destructive action of the senile atrophic process, in any case until the expressive speech is preserved. Storage of the information acquired before the appearance of the symptoms of dementia is unlikely to depend on the degree of its personality importance. Before it becomes strongly manifest, senile dementia does not prevent the stamping on the person's memory, at least of part of new information (possibly, of only emotionally significant). Such material may also be stored in the patients' memory even in case of pronounced dementia. Difficulties in active reproduction of the ideas available in memory stores can already be seen at the early stages, becoming more remarkable as the disease progresses.


Patient-specific Boolean models of signalling networks guide personalised treatments.
Prostate cancer is the second most occurring cancer in men worldwide. To better understand the mechanisms of tumorigenesis and possible treatment responses, we developed a mathematical model of prostate cancer which considers the major signalling pathways known to be deregulated. We personalised this Boolean model to molecular data to reflect the heterogeneity and specific response to perturbations of cancer patients. A total of 488 prostate samples were used to build patient-specific models and compared to available clinical data. Additionally, eight prostate cell line-specific models were built to validate our approach with dose-response data of several drugs. The effects of single and combined drugs were tested in these models under different growth conditions. We identified 15 actionable points of interventions in one cell line-specific model whose inactivation hinders tumorigenesis. To validate these results, we tested nine small molecule inhibitors of five of those putative targets and found a dose-dependent effect on four of them, notably those targeting HSP90 and PI3K. These results highlight the predictive power of our personalised Boolean models and illustrate how they can be used for precision oncology.


[Left ventricular functions in patients with cardiac syndrome X: a tissue Doppler study].
The aim of the study was to compare diagnostic accuracy of tissue Doppler imaging (TDI) and conventional Doppler echocardiography in diagnosis of left ventricular diastolic dysfunction in patients with cardiac syndrome X. Our study was designed as cross-sectional study. In our study, we compared 35 patients with cardiac syndrome X (19 female, mean age 47.2+/- 7.3 years) with 33 healthy persons as control group (18 female, mean age 49.5+/- 7.1 years) with no coronary artery disease and having no ischemic complaints or findings at exercise test. Left ventricular systolic function was found by considering mean values of modified Simpson method for left ventricular ejection fraction and TDI assessment of systolic wave peak velocity. The diastolic function of left ventricle was assessed with conventional echocardiography and TDI. Unpaired t test for independent samples or Mann-Whitney U test were used for comparison of continuous variables, Chi square test - for comparison of categorical variables. To define the capability of predicting diastolic dysfunction for conventional Doppler echocardiography and tissue Doppler imaging ROC curve analysis was applied. Left ventricular ejection fraction and systolic wave peak velocity were similar for both groups. Conventional Doppler echocardiographic measurements for left ventricular diastolic functions delineated the more frequent presence of diastolic dysfunction in cardiac syndrome X group As compared with controls (48% vs 18%; p<0.01). When both methods used for assessing diastolic dysfunction, it was found more apparent (66% vs 24%; p<0.01). When ROC curve was drawn for conventional Doppler echocardiography the AUC was 0.623, the sensitivity and the specificity were 49% and 76%, respectively. When the same was done for TDI the values were AUC=0.669, the sensitivity - 66% and the specificity - 68%. Our study revealed the deterioration of left ventricular diastolic function in patients with cardiac syndrome X. We found TDI echocardiography was more sensitive to delineate left ventricular diastolic dysfunction in this category of patients when compared with conventional Doppler echocardiography.


Molecular detection and associated risk factors of Anaplasma marginale, A. ovis and A. platys in sheep from Algeria with evidence of the absence of A. phagocytophilum.
Anaplasma species are obligate intracellular rickettsial pathogens that cause significant diseases in animals and humans. Despite their importance, limited information on Anaplasma infections in Algeria has been published thus far. This study aimed to assess the infection rate, characterize Anaplasma species, and identify associated risk factors in selected sheep farms across Oum El Bouaghi region in Algeria. In 2018, we collected 417 blood samples from sheep (Ovis aries) and performed molecular characterization of Anaplasma species infecting these animals. This characterization involved the use of 16S rRNA, msp2, rpoB, and msp5 genes, which were analyzed through nested PCR, qPCR, cPCR, DNA sequencing, and subsequent phylogenetic analysis. Our findings revealed infection rates of 12.7 % for Anaplasma species detected, with Anaplasma ovis at 10.8 %, Anaplasma marginale at 1.7 %, and Anaplasma platys at 0.2 %. Interestingly, all tested animals were found negative for Anaplasma phagocytophilum. Statistical analyses, including the Chi-square test and Fisher exact test, failed to establish any significant relationships (p > 0.05) between A. ovis and A. platys infections and variables such as age, sex, sampling season, and tick infestation level. However, A. marginale infection exhibited a significant association with age (p < 0.05), with a higher incidence observed in lambs (5.2 %) compared to other age groups. Remarkably, this study represents the first molecular detection of A. platys and A. marginale in Algerian sheep. These findings suggest that Algerian sheep may serve as potential reservoirs for these pathogens. This research contributes valuable insights into the prevalence and characteristics of Anaplasma infections in Algerian sheep populations, emphasizing the need for further investigation and enhanced surveillance to better understand and manage these diseases.


Endoscope-assisted spinal decompression surgery for lumbar spinal stenosis.
The authors undertook this study to document the clinical outcomes of microendoscopic laminotomy, a minimally invasive decompressive surgical technique using spinal endoscopy for lumbar decompression, in patients with lumbar spinal stenosis (LSS). A total of 366 patients were enrolled in the study and underwent microendoscopic laminotomy between 2007 and 2010. Indications for surgery were single- or double-level LSS, persistent neurological symptoms, and failure of conservative treatment. Microendoscopy provided wide visualization through oblique lenses and allowed bilateral decompression via a unilateral approach, through partial resection of the base of the spinous process, thereby preserving the supraspinous and interspinous ligaments and contralateral musculature. Clinical symptoms and signs of low-back pain were evaluated prior to and following surgical intervention by applying the Japanese Orthopaedic Association (JOA) scoring system, Roland-Morris Disability Questionnaire (RMDQ), Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), and 36-Item Short Form Health Survey (SF-36). These items were evaluated preoperatively and 2 years postoperatively. Effective circumferential decompression was achieved in all patients. The 2-year follow-up evaluation was completed for 310 patients (148 men and 162 women; mean age 68.7 years). The average recovery rate based on the JOA score was 61.3%. The overall results were excellent in 34.9% of the patients, good in 34.9%, fair in 21.7%, and poor in 8.5%. The mean RMDQ score significantly improved from 11.3 to 4.8 (p < 0.001). In all categories of both JOABPEQ and SF-36, scores at 2 years' follow-up were significantly higher than those obtained before surgery (p < 0.001). Twelve surgery-related complications were identified: dural tear (6 cases [1.9%]), wrong-level operation (1 [0.3%]), transient neuralgia (4 [1.3%]), and infection (1 [0.3%]). All patients recovered, and there were no serious postoperative complications. Microendoscopic laminotomy is a safe and very effective minimally invasive surgical technique for the treatment of degenerative LSS.


The up-to-date review of epidemiological pancreatic neuroendocrine tumors in Japan.
Pancreatic neuroendocrine tumors (PNETs) were considered an extremely rare disease. However, in recent years, the number of patients with PNET has increased rapidly. According to an epidemiological survey conducted in Japan, the number of treated patients with PNETs in 2010 was approximately 1.2-times that in 2005, and the number of new incidences of non-functional PNETs in 2010 was approximately 1.7-times that in 2005. Among functional PNETs, insulinoma was most prevalent, followed by gastrinoma. To diagnose PNETs, correct histological diagnosis is most important. According to the World Health Organization 2010 classification criteria, neuroendocrine tumors (NETs) are categorized into well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NECs accounted for 7.6% of all NETs, and functional and non-functional PNETs accounted for 2.1% and 10.1%, respectively. Patients with distant metastasis accounted for 19.9%, and those with multiple endocrine neoplasia type 1 accounted for 4.3%. When treating PNETs, it is necessary to correctly evaluate the functionality and progression of tumors, the presence or absence of metastasis, and the degrees of differentiation and malignant potential of tumors. A new registration system from the Japan Neuroendocrine Tumor Society will start to be used in 2015, which will help further dissemination of Japanese epidemiological information to the world.


[Clinical and pathogenetic features of recurrent and acute peptic ulcer in acute coronary syndrome].
Clinico-pathogenetic characteristics of recurrent ulcer disease and acute ulcers were studied in 84 patients with unstable coronary heart disease (CHD). It was found that a relapse of ulcer disease (UD) in CHD presents with moderate abdominal pain without a typical circadian rhythm and with dyspepsia registered, as a rule, for 2 weeks. Acute ulcers often manifested with weak epigastric pain and symptoms of gastric dyspepsia observed usually for several days of hospital treatment. Gastroduodenal bleeding had obscure clinical picture but complicated recurrent UD and acute ulcers in 29.4 and 50% cases, respectively. The recurrence of UD in CHD developed in the presence of focal thrombohemorrhagic disorders of microcirculation in the tissues of gastroduodenal zone, high activity of the acid-peptic factor, low mucus production, hypomotor gastric dyskinesia, detection of Helicobacter pylori (HP). Acute ulcers are most frequently associated with focal thromboischemic disorders of end blood flow, minor changes in pepsin and mucoprotein production, prominent hypomotor gastric dyskinesia and, in 10% cases, HP.


Mitoquinone ameliorates pressure overload-induced cardiac fibrosis and left ventricular dysfunction in mice.
Increasing evidence indicates that mitochondrial-associated redox signaling contributes to the pathophysiology of heart failure (HF). The mitochondrial-targeted antioxidant, mitoquinone (MitoQ), is capable of modifying mitochondrial signaling and has shown beneficial effects on HF-dependent mitochondrial dysfunction. However, the potential therapeutic impact of MitoQ-based mitochondrial therapies for HF in response to pressure overload is reliant upon demonstration of improved cardiac contractile function and suppression of deleterious cardiac remodeling. Using a new (patho)physiologically relevant model of pressure overload-induced HF we tested the hypothesis that MitoQ is capable of ameliorating cardiac contractile dysfunction and suppressing fibrosis. To test this C57BL/6J mice were subjected to left ventricular (LV) pressure overload by ascending aortic constriction (AAC) followed by MitoQ treatment (2 µmol) for 7 consecutive days. Doppler echocardiography showed that AAC caused severe LV dysfunction and hypertrophic remodeling. MitoQ attenuated pressure overload-induced apoptosis, hypertrophic remodeling, fibrosis and LV dysfunction. Profibrogenic transforming growth factor-β1 (TGF-β1) and NADPH oxidase 4 (NOX4, a major modulator of fibrosis related redox signaling) expression increased markedly after AAC. MitoQ blunted TGF-β1 and NOX4 upregulation and the downstream ACC-dependent fibrotic gene expressions. In addition, MitoQ prevented Nrf2 downregulation and activation of TGF-β1-mediated profibrogenic signaling in cardiac fibroblasts (CF). Finally, MitoQ ameliorated the dysregulation of cardiac remodeling-associated long noncoding RNAs (lncRNAs) in AAC myocardium, phenylephrine-treated cardiomyocytes, and TGF-β1-treated CF. The present study demonstrates for the first time that MitoQ improves cardiac hypertrophic remodeling, fibrosis, LV dysfunction and dysregulation of lncRNAs in pressure overload hearts, by inhibiting the interplay between TGF-β1 and mitochondrial associated redox signaling.


Evaluation of a radioimmunoassay and establishment of a reference interval for salivary cortisol in healthy subjects in Denmark.
A commercial radioimmunoassay (RA) for salivary cortisol was evaluated using certified reference material in water and spiked to pooled saliva in the range 2.1-89.1 nmol/L. A variance component model for describing the effects of age, body mass index (BMI), diurnal variation, gender, days of sick leave during the past year, and smoking habits was established. Reference intervals for salivary cortisol in 120 healthy individuals performing their routine work were established according to the International Union of Pure and Applied Chemistry (IUPAC) and the International Federation of Clinical Chemistry (IFCC). The method evaluation of the certified reference material in water did not show any bias of the method, i.e. recovery was 97% [CI: 94%; 100.9%]. LOD (detection limit) was 1.59 nmol/L. The ratio between analytical and within-subject variation (CVa/CVi) was 0.14, indicating that the method was adequate for measurement in healthy subjects. Reference intervals were estimated to be from 3.6 to 35.1 nmol/L for samples at the time of awakening (05.27-07.27), 7.6-39.4 nmol/L for peak level in saliva samples collected 20 min after awakening (05.47-07.47), and LOD 10.3 nmol/L for late afternoon samples (17.00-19.00). Reactivity (increase from awakening to 20 min after awakening) was estimated to be 82% [CI: -179; 345%] and recovery (decrease from 20 min after awakening to 18.00) to be 80% [CI: 51; 109%]. Eighteen percent of the subjects showed a decrease in cortisol in saliva from awakening to 20 min after awakening. Salivary cortisol was not affected by age, body mass index, gender, smoking habits or days of sick leave during the past year.


Expressional reprogramming of survival pathways in rat cardiocytes by neuregulin-1beta.
Neuregulin/ErbB2-induced kinase signaling provides essential survival and protection clues for functional integrity of the adult heart and skeletal muscle. To define the regulatory pathways involved in neuregulin-dependent muscle cell survival, we set out to map the largely unknown transcript targets of this growth/differentiation factor in cardiocytes. Freshly isolated adult primary rat cardiocytes were treated for 24 h with recombinant human neuregulin-1beta (NRG-1beta, 30 ng/ml). Transcript level alterations in NRG-1beta-treated and control cardiocytes (n = 6) were identified with Atlas Rat Toxicology 1.2 cDNA arrays (BD Clontech) and established permutation L1 regression analysis. Selected transcriptional adjustments were confirmed by RT-PCR and Western blotting. Involvement of MAPK pathways was verified with the inhibitor PD-98059. Application of the single dose of NRG-1beta to quiescent cardiocytes induced expressional reprogramming of distinct cellular processes. This response included a prominent 50-100% increase in transcripts of multiple redox systems. It also involved a comparable mRNA augmentation of protein synthetic and folding factors together with augmented message for the trigger of cardiac hypertrophy, cyclin D1 (CCND1). First evidence for a role of neuregulin in promotion of mitochondrial turnover, voltage-gated ion channel expression, and the suppression of fatty acid transporter mRNAs was revealed. Subsequent analysis confirmed a corresponding upregulation of redox factor proteins thioredoxin and the thioredoxin reductase 1, GSTP-1, and CCND1 and demonstrated downregulation of the related transcripts by PD-98059 in neuregulin-stimulated cultures. These MAPK-dependent expressional adjustments point to novel oxidative defense and hypertrophy pathways being involved in the longer lasting protective function of neuregulin in the heart.


From probiotics to therapeutics: another step forward?
Preclinical studies with probiotics continue to unravel mechanisms of cytoprotection and suggest that approaches utilizing microbial products as therapeutics in acute and chronic gastrointestinal disorders could be effective. However, clinical trials using these bacteria have thus far been inconsistent. In this issue of the JCI, Yan et al. describe a novel mechanism of cytoprotection by p40, a soluble product of Lactobacillus rhamnosus GG, mediated via EGFR. The efficacy of p40 in three models of chemically induced colitis indicates tremendous therapeutic potential, though this finding will need to be verified in human patients.


Deep sequencing analysis reveals temporal microbiota changes associated with development of bovine digital dermatitis.
Bovine digital dermatitis (DD) is a leading cause of lameness in dairy cattle throughout the world. Despite 35 years of research, the definitive etiologic agent associated with the disease process is still unknown. Previous studies have demonstrated that multiple bacterial species are associated with lesions, with spirochetes being the most reliably identified organism. This study details the deep sequencing-based metagenomic evaluation of 48 staged DD biopsy specimens collected during a 3-year longitudinal study of disease progression. Over 175 million sequences were evaluated by utilizing both shotgun and 16S metagenomic techniques. Based on the shotgun sequencing results, there was no evidence of a fungal or DNA viral etiology. The bacterial microbiota of biopsy specimens progresses through a systematic series of changes that correlate with the novel morphological lesion scoring system developed as part of this project. This scoring system was validated, as the microbiota of each stage was statistically significantly different from those of other stages (P < 0.001). The microbiota of control biopsy specimens were the most diverse and became less diverse as lesions developed. Although Treponema spp. predominated in the advanced lesions, they were in relatively low abundance in the newly described early lesions that are associated with the initiation of the disease process. The consortium of Treponema spp. identified at the onset of disease changes considerably as the lesions progress through the morphological stages identified. The results of this study support the hypothesis that DD is a polybacterial disease process and provide unique insights into the temporal changes in bacterial populations throughout lesion development.


The assessment of psychopathology among traumatized refugees: measurement invariance of the Harvard Trauma Questionnaire and the Hopkins Symptom Checklist-25 across five linguistic groups.
Background: Questionnaires are widely used to assess the mental health status of refugees, whereas their construct validity largely remains unexplored. Objective: This study examined the construct validity of two widely-used instruments for the assessment of PTSD symptoms (Harvard Trauma Questionnaire [HTQ]; 16 items) and symptoms of anxiety and depression (Hopkins Symptom Check list-25 [HSCL-25]; 25 items) among Dutch and refugee patients with different linguistic backgrounds. Method: We applied exploratory factor analyses and measurement invariance analyses to test construct validity.Participants (n =1 256) were divided into five linguistic groups defined by language family, including four non-western linguistic groups (Indo-Iranian [n = 262], Niger-Congo [n = 134], Semitic [n = 288], and South Slavic languages [n = 199]) and one western linguistic group (Germanic languages; Dutch [n = 373]). Results: Exploratory factor analysis yielded a 3-factor structure of the HTQ and a 2-factor structure of the HSCL-25. Measurement invariance 20 analyses on the HTQ showed strong measurement invariance across the groups of refugee patients. However, Dutch patients reported milder symptom severity on most items of the HTQ. Measurement invariance analyses on the HSCL-25 (not conducted in Dutch patients) indicated partial strong measurement invariance across refugee patients. Conclusion: We conclude that mental health constructs measured by the HTQ and the HSCL25 25 are to a large extent interpreted in a similar way by refugee patients. This indicates that these instruments can be applied in non-western refugee patient populations, and that local idioms of distress and inherent response patterns may not play a major role when applying the HTQ and the HSCL-25 in these populations. Yet, whereas meaningful comparisons of observed PTSD and depression scores between groups of refugee patients with different non30 western linguistic background are feasible, comparisons between patients with a western and non-western linguistic background, as well as comparisons of anxiety scores, are likely to be biased. Future studies need to establish whether the commonly used cut-off scores of both questionnaires apply for refugee patients with non-western linguistic backgrounds.


[A comparison of pyrophosphatase and peroxidase as markers in the immunoenzyme analysis of the tick-borne encephalitis virus and antibodies to it].
The authors compare the sensitivities of pyrophosphatase and peroxidase conjugates with immunoglobulins in assays of tick-borne encephalitis (TBE) virus antigens and anti-TBE antibodies in human sera. Pyrophosphatase conjugates are similar to peroxidase ones in their enzymic and immunochemical characteristics and are not inferior to them in sensitivity in titration of antibodies and superior in assays with antigens. A number of advantages of pyrophosphatase conjugates, i.e. a simple preparation procedure, stable substrate and enzymic reaction product, color range convenient for visual recording, etc., make these conjugates preferable vs. the peroxidase ones and recommend them for wide use at diagnostic laboratories.


Intricate environment-modulated genetic networks control isoflavone accumulation in soybean seeds.
Soybean (Glycine max [L] Merr.) seed isoflavones have long been considered a desirable trait to target in selection programs for their contribution to human health and plant defense systems. However, attempts to modify seed isoflavone contents have not always produced the expected results because their genetic basis is polygenic and complex. Undoubtedly, the extreme variability that seed isoflavones display over environments has obscured our understanding of the genetics involved. In this study, a mapping population of RILs with three replicates was analyzed in four different environments (two locations over two years). We found a total of thirty-five main-effect genomic regions and many epistatic interactions controlling genistein, daidzein, glycitein and total isoflavone accumulation in seeds. The use of distinct environments permitted detection of a great number of environment-modulated and minor-effect QTL. Our findings suggest that isoflavone seed concentration is controlled by a complex network of multiple minor-effect loci interconnected by a dense epistatic map of interactions. The magnitude and significance of the effects of many of the nodes and connections in the network varied depending on the environmental conditions. In an attempt to unravel the genetic architecture underlying the traits studied, we searched on a genome-wide scale for genomic regions homologous to the most important identified isoflavone biosynthetic genes. We identified putative candidate genes for several of the main-effect and epistatic QTL and for QTL reported by other groups. To better understand the underlying genetics of isoflavone accumulation, we performed a large scale analysis to identify genomic regions associated with isoflavone concentrations. We not only identified a number of such regions, but also found that they can interact with one another and with the environment to form a complex adaptable network controlling seed isoflavone levels. We also found putative candidate genes in several regions and overall we advanced the knowledge of the genetics underlying isoflavone synthesis.


Meningitis in adults: diagnosis and management.
Bacterial meningitis is a medical emergency. All clinicians who provide acute medical care require a sound understanding of the priorities of managing a patient with suspected meningitis during the first hour. These include obtaining blood cultures, performing lumbar puncture and initiating appropriate therapy, while avoiding harmful delays such as those that result from not administering treatment until neuroimaging has been performed. Despite the increasing availability of newer diagnostic techniques, the interpretation of cerebrospinal fluid parameters remains a vital skill for clinicians. International and local guidelines differ with regard to initial empirical therapy of bacterial meningitis in adults; the North American guideline recommends ceftriaxone and vancomycin for all patients, while the Australian, UK and European guidelines recommend that vancomycin only be added for patients who are more likely to have pneumococcal meningitis or who have a higher likelihood of being infected with a strain of Streptococcus pneumoniae with reduced susceptibility to ceftriaxone. Patients with risk factors for Listeria meningitis also require an anti-Listeria agent, such as benzylpenicillin, to be added to this treatment regimen. Dexamethasone should be a routine component of empirical therapy due to its proven role in reducing morbidity and mortality from pneumococcal meningitis.


Intraoperative sonography of intraspinal tumors: initial experience.
Real-time sonography during surgery for intraspinal tumors is capable of demonstrating the extent of the tumor, its relation to the spinal cord, and the internal morphology of both the tumor and the cord. Such information is not obtainable intraoperatively by any other imaging method. It is especially valuable when all or a part of the tumor is anterior to the cord and therefore not visible to the surgeon without exploration and the attendant risk of spinal cord injury. Direct contact with the spinal cord is not necessary for sonographic imaging.


Attitudes and Perceptions Toward the Use of Medical Marijuana by Glaucoma Specialists.
With expanding legality of medical marijuana (MMJ) in the United States, it is important for ophthalmologists to have greater understanding of the implications of MMJ and glaucoma treatment and how it can impact their patients. Previous work has demonstrated that inhaled tetrahydrocannabinol can lower intraocular pressure. The stance of the American Glaucoma Society (AGS) is that MMJ is not an acceptable treatment for glaucoma. The purpose of this study is to evaluate the glaucoma specialists' perceptions and attitudes toward the use of MMJ for glaucoma. An electronic survey was sent to members of the AGS which addressed attitudes and perceptions on the use of MMJ in the management of glaucoma. Study questions included practitioner demographics, previous experiences with patients discussing the topic, prescribing patterns, and knowledge regarding the use of MMJ for the treatment of glaucoma. Thirty-seven percent of respondents reported having patients who cited using MMJ for their glaucoma, and 38% of respondents were asked about MMJ by their patients at least once per week. Fifty-five percent of respondents had patients who asked them for MMJ prescriptions. When asked if they felt if there was a possible role for marijuana in the management of glaucoma patients, 27% of survey takers responded yes. Fourteen percent of survey respondents kept information on MMJ in their office. Finally, 76% of participants responded they would be interested in additional education on the topic. Over 25% of the glaucoma specialists responded that MMJ had a role in the treatment of glaucoma, despite the recommendation of the professional society. This group was least likely to have received education on the topic. Given the expanding legality and curiosity of patients with regards to marijuana in the United States, it is important for ophthalmologists to have a greater understanding of the implications of marijuana in glaucoma.


Multidisciplinary clinical guidance on trastuzumab deruxtecan (T-DXd)-related interstitial lung disease/pneumonitis-Focus on proactive monitoring, diagnosis, and management.
Trastuzumab deruxtecan (T-DXd; DS-8201) is an antibody-drug conjugate targeting human epidermal growth factor receptor 2. Interstitial lung disease (ILD)/pneumonitis is an adverse event associated with T-DXd; in most cases, it is low grade (grade ≤ 2) and can be treated effectively but may develop to be fatal in some instances. It is important to increase patient and provider understanding of T-DXd-related ILD/pneumonitis to improve patient outcomes. Drug-related ILD/pneumonitis is a diagnosis of exclusion; other possible causes of lung injury/imaging findings must be ruled out for an accurate diagnosis. Symptoms can be nonspecific, and identifying early symptoms is challenging; therefore, diagnosis is often delayed. We reviewed characteristics of patients who developed T-DXd-related ILD/pneumonitis and its patterns, produced multidisciplinary guidelines on diagnosis and management, and described areas for future investigation. Ongoing studies are collecting data on T-DXd-related ILD/pneumonitis to further our understanding of its clinical patterns and mechanisms. SEARCH STRATEGY AND SELECTION CRITERIA: References were identified based on the guidelines used by the authors in treating interstitial lung disease and pneumonitis. Searches of the authors' own files were also completed. A search of PubMed with the search terms (trastuzumab deruxtecan) AND (interstitial lung disease) AND (guidelines) was conducted on November 1, 2021, with no restrictions based on publication date, and the two articles yielded by the search were included.


[Difference between transcortical sensory aphasia following the left frontal lesion and transcortical sensory aphasia following the left posterior lesion].
We assessed the difference between transcortical sensory aphasia (TCSA) following the left frontal lesions (F-TCSA) and TCSA following the left posterior lesions (P-TCSA). All the patients were right-handed and the 7 patients had the lesions in the only frontal lobe and the 10 patients had the lesions only in the left temporo-parieto-occipital regions. We administered pointing tasks, using 90 line drawings representing single nouns. We presented 6 line drawings a pointing board, and we used two kinds of pointing boards: one showed the line drawings each belonging to different categories (random categorized pointing task), the other showed the line drawings each belonging to only either two different categories (two categorized pointing task) and we presented 15 pointing boards each alternatively. The result was that regarding the patients of P-TCSA showed different number of correct answers between the random categorized pointing task and the two categorized pointing task with statistical significance. Regarding the patients of F-TCSA showed no difference between them. The results indicated that disturbance of P-TCSA on the pointing task was the disturbance of semantic process per se. And the disturbance of F-TCSA on the pointing task was that of not only semantic process but also the whole process including comprehending the presented words, searching the line drawings, comparing the line drawings with the presented word and final selection, which demanded persistent multiple memory process consistent with working memory.


Combining a molecular profile with a clinical and pathological profile: biostatistical considerations.
The use of molecular markers and gene expression profiling provides a promising approach for improving the predictive accuracy of current prognostic indices for predicting which patients with non-muscle-invasive bladder cancer will progress to muscle-invasive disease. There are many statistical pitfalls in establishing the benefit of a multigene expression classifier during its development. First, there are issues related to the identification of the individual genes and the false discovery rate, the instability of the genes identified and their combination into a classifier. Secondly, the classifier should be validated, preferably on an independent data set, to show its reproducibility. Next, it is necessary to show that adding the classifier to an existing model based on the most important clinical and pathological factors improves the predictive accuracy of the model. This cannot be determined based on the classifier's hazard ratio or p-value in a multivariate model, but should be assessed based on an improvement in statistics such as the area under the curve and the concordance index. Finally, nomograms are superior to stage and risk group classifications for predicting outcome, but the model predicting the outcome must be well calibrated. It is important for investigators to be aware of these pitfalls in order to develop statistically valid classifiers that will truly improve our ability to predict a patient's risk of progression.


The impact of breast cancer on mother-child relationships in Korea.
For families with dependent children, the situational crisis of a cancer diagnosis may compound the developmental task of parenting. This study aimed to explore the impact of breast cancer on Korean mothers and their children following diagnosis. Korean women diagnosed with breast cancer at 50 years or younger more than a year ago were recruited by posting announcements at a breast cancer clinic and through referrals and snowball sampling. A one-time in-depth interview ranging from 60 to 90 min was conducted and data were transcribed verbatim for content analysis. Five themes emerged from the data: (1) The delicate balance of being able to focus on self, which also was a conflicting factor in their relationship with children; (2) The continuing challenge of taking care of children, which was closely linked to supports, health condition, and cultural notions of parenting and lingering stigma; (3) The importance of informing children in a timely manner; (4) An overall shift in attitudes towards raising children as independent beings; and (5) Relinquishing and re-envisioning the future for their children and themselves. Breast cancer brings new challenges in mother-child relationships with culturally framed issues. Findings can guide healthcare providers in giving relevant anticipatory guidance for women diagnosed with breast cancer and in considering family-focused psychosocial and behavioral interventions for families with breast cancer.


A descriptive study of ciguatera fish poisoning in Cook Islands dogs and cats: Exposure history, clinical signs, and formulation of a case definition.
Ciguatera fish poisoning (CFP) is a multisystem toxicosis caused by the ingestion of warm water marine species. Dogs and cats are susceptible to CFP, but there is little published and much unknown about the condition in these species. This study aims to describe the syndrome of CFP in dogs and cats and to develop a case definition. Six years (March 2011-February 2017) of medical records from the Esther Honey Foundation Animal Clinic (the only veterinary clinic in the Cook Islands during the study period) were reviewed to identify cases of CFP. Data relating to exposure history and clinical signs were collected. Two hundred forty-six cases of CFP were identified, comprising 165 dogs and 81 cats. Fish ingestion was documented in 29% of cases. Reef/lagoon fish and moray eels were most commonly implicated. The toxicosis was characterized by motor dysfunction with a high frequency of ataxia and paresis/paralysis/recumbency. Respiratory and gastrointestinal systems were also affected, especially in canine CFP cases. A multi-tiered case definition and a diagnostic algorithm for CFP in dogs and cats were developed based upon the findings of this study and a review of the existing literature. This case series is the largest study of canine and feline CFP to date. It documents the exposure history of cases and describes in detail clinical signs of the toxicosis. It also proposes a system of case classification that has the potential to both assist the diagnosis of CFP and facilitate future surveillance and research activities.