Is low-risk hypertension fact or fiction? cardiovascular risk profile in the TROPHY study.
The Trial of Preventing Hypertension (TROPHY) Study is designed to establish whether treating high normal blood pressure with a low-dose angiotensin receptor blocker, candesartan cilexetil, for 2 years reduces the rate of progression to hypertension compared with placebo treatment over a 4-year observation period. We are presenting the baseline cardiovascular risk factor profile of the 809 subjects randomized in the TROPHY Study. The risk factors in this analysis were as follows: cholesterol >or=200 mg/dl; LDL-cholesterol >or=160 mg/dL; HDL-cholesterol <or=40 mg/dL (for men), <or=50 mg/dL (for women); triglycerides >or=150 mg/dL; body mass index >or=25 kg/m2 (overweight and obese), fasting insulin >or=20 mU/mL; heart rate >or=80 beats/min; hematocrit >or=43.5 % (men) and >or=41.2% (women). The TROPHY Study is a 4-year randomized, placebo-controlled, multicenter clinical trial of 809 subjects with high normal blood pressure (BP), which is currently in progress. The participants of the TROPHY study (mean age 49+/-8.1 years) with high normal BP (mean 134+/-4/85+/-4 mm Hg) had additional cardiovascular risk factors. Of the group, 96% had at least one, 81% had two or more, and 13% had five or more additional risk factors. Our data from individuals with high normal BP suggests clearly that the risk of cardiovascular disease begins to rise before the diagnosis of hypertension is evident. The overall risk in such subjects reflects both the rising BP and other concurring factors. It appears that truly low-risk hypertension only rarely exists.


Faecal pollution of surface waters in Jakarta.
Profuse numbers of Enterobacteriaceae were found in samples of surface waters from the Ciliwung River and adjoining canals which criss-cross metropolitan Jakarta and are used widely for domestic purposes by the poorer sections of its population. 15 of the 20 specimens gres E. coli, Klebsiella were isolated from seven and Citrobacter from four. Using enrichment culture procedures, Salmonella sp. were grown from 10 (48%) of 21 water samples examined, and 12 (63%) of aquatic sediments collected at the same sites. Altogether 14 serotypes and 37 Salmonella isolations were recorded. This high degree of faecal contamination of the environment is a major cause of the immense problem of gastro-intestinal infections in that city and probably in many similar cities in developing countries in the tropics.


Temporal trend of polychlorinated biphenyls contamination in the northwestern Arabian Gulf - Evidence from sediment records.
This study provides an insight into the polychlorinated biphenyls (PCBs) inventories in the sediments of the northwestern Arabian/Persian Gulf. PCBs can be used as chemical markers that correlate with historical events in the region, to estimate the sedimentation rates in the northern Gulf, and to determine the sources of pollutants in the study area. The concentrations of PCBs were generally patchy in sediments. At Station 1 the ΣPCB concentrations generally fluctuated between 0.100 and 0.400 ng g-1 dw throughout the depositional history measured in a sediment core. There were four peaks in the ΣPCB profile corresponding to 1969, 1979, 1983 and 1991. Station 2 showed a prominent peak at depth of 25 cm. The concentrations of the ΣPCBs and ΣICE congeners at this depth were 28 and 12 ng g-1 dw respectively. Concentrations then dropped dramatically thereafter by a factor of 4. The ΣPCB concentrations at Station 3 were very low compared to the concentrations measured at Stations 1 and 2. The PCB concentration in Core 4 which was taken from open waters was 2-3 orders of magnitude lower than those in the other coastal cores. However, a 1990-91 peak was omnipresent in these cores. There is no record of PCB production within the Gulf region, and PCB releases into the Kuwait marine environment are likely to originate from their use in products. These maxima in early-1990s can be correlated to inputs from war-related activities, including the reported destruction of PCB-containing transformers and military equipment during the occupation of Kuwait. None of the recent sediment core sections at the four stations had a ΣPCB concentration near the effects range-median (ERM) concentration of 180 ng g-1, or permissible exposure limits (PEL) of 189 ng g-1, or were above the effect range-low (ERL) values of 22.7 ng g-1.


Emerging prospects of extracellular vesicles for brain disease theranostics.
In the past decade, bio-nanoparticles inspired by nature with advantageous properties have attracted extensive interest for accurate diagnosis and effective treatment. Extracellular vesicles (EVs) are nanosized naturally derived vesicles which contain a variety of bioactive molecules reflecting their cell of origin. Emerging advances in the field of EV nanotechnology bring along novel promises for blooming the development of EV-based therapeutics. Studies of the EV features in central nervous system physiology and brain disease pathology explosively promote the idea of harnessing these endogenous vesicles as a promising strategy for brain disease theranostics. These nanosized vesicles with natural blood-brain barrier-crossability, remarkable physicochemical properties and excellent biocompatibility are considered a prime candidate as an intelligent vehicle for brain therapeutic and drug delivery applications. Here, this review provides an overview on the characteristics, isolation and internalization of EVs, and the recent progresses in the strategies and methodologies of modified EVs for effective cargo-loading is presented. The potential theranostics applications of EVs in brain diseases are further discussed by presenting representative examples. The challenges and obstacles of current studies are also presented, and perspectives for successful clinical translation are further discussed.


Effect of psychotomimetics and some putative anxiolytics on stress-induced hyperthermia.
Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip). At higher dose, CL 218872 (100 mg/kg, os) and tracazolate (12.5 mg/kg, ip) lose their activity. PK 9084 (5-40 mg/kg, ip) and CGS 9896 (2-20 mg/kg, both ip and os) were also ineffective in preventing SIH. The anti-hyperthermic effect of CL 218872 (25 mg/kg) and tracazolate (7.5 mg/kg) was blocked by the benzodiazepine antagonist Ro 15-1788 (15 mg/kg), CGS 9896 (10 mg/kg, os) also reversed the effect of CL 218872 (25 mg/kg) on SIH. Differently from anxiolytics, MK-801 (0.5-1 mg/kg, os), PCP (2.5 mg/kg, ip) and d-amphetamine (10 mg/kg, ip) evoked hyperthermia in the first set of mice and prevented a further stress-induced rise of body temperature in the last set of mice.


Reinterpretation of oceanic 230Th profiles based on decadal export productivity (2003-2010).
Understanding 230Th distributions in the global ocean is important to support and guide the use of this important radioactive nuclide in multiple aspects of oceanographic research, and this issue is now revisited. Based on estimates of export productivity (EP) over 2003-2010 and assuming 230Th scavenging at equilibrium at seven Pacific stations where linear 230Th profiles are found, an empirical equilibrium-state 230Th-scavenging versus EP correlation is established. This correlation demonstrates the relationship between 230Th-scavenging intensity and EP in the absence of advection. With this correlation, other 230Th profiles from global oceans are reinterpreted. My findings provide alternative explanations of signals carried by 230Th distributions with regard to advection, by a reassessment of the 230Th deficits in deep waters. Such an equilibrium-state 230Th-scavenging versus EP correlation provides a basis for convenient parameterization for use in 3D modeling studies of the 230Th distributions.


Supporting recovery in patients with psychosis through care by community-based adult mental health teams (REFOCUS): a multisite, cluster, randomised, controlled trial.
Mental health policy in many countries is oriented around recovery, but the evidence base for service-level recovery-promotion interventions is lacking. We did a cluster, randomised, controlled trial in two National Health Service Trusts in England. REFOCUS is a 1-year team-level intervention targeting staff behaviour to increase focus on values, preferences, strengths, and goals of patients with psychosis, and staff-patient relationships, through coaching and partnership. Between April, 2011, and May, 2012, community-based adult mental health teams were randomly allocated to provide usual treatment plus REFOCUS or usual treatment alone (control). Baseline and 1-year follow-up outcomes were assessed in randomly selected patients. The primary outcome was recovery and was assessed with the Questionnaire about Processes of Recovery (QPR). We also calculated overall service costs. We used multiple imputation to estimate missing data, and the imputation model captured clustering at the team level. Analysis was by intention to treat. This trial is registered, number ISRCTN02507940. 14 teams were included in the REFOCUS group and 13 in the control group. Outcomes were assessed in 403 patients (88% of the target sample) at baseline and in 297 at 1 year. Mean QPR total scores did not differ between the two groups (REFOCUS group 40·6 [SD 10·1] vs control 40·0 [10·2], adjusted difference 0·68, 95% CI -1·7 to 3·1, p=0·58). High team participation was associated with higher staff-rated scores for recovery-promotion behaviour change (adjusted difference -0·4, 95% CI -0·7 to -0·2, p=0·001) and patient-rated QPR interpersonal scores (-1·6, -2·7 to -0·5, p=0·005) at follow-up than low participation. Patients treated in the REFOCUS group incurred £1062 (95% CI -1103 to 3017) lower adjusted costs than those in the control group. Although the primary endpoint was negative, supporting recovery might, from the staff perspective, improve functioning and reduce needs. Implementation of REFOCUS could increase staff recovery-promotion behaviours and improve patient-rated recovery. National Institute for Health Research.


Multiplex PCR assay for direct identification of group B streptococcal alpha-protein-like protein genes.
We developed a group B streptococcus multiplex PCR assay which allows, by direct analysis of the amplicon size, determination of the surface protein antigen genes of alpha-C protein, epsilon protein, Rib, Alp2, Alp3, and Alp4. The multiplex PCR assay offers a rapid and simple method of subtyping Streptococcus agalactiae based on surface protein genes.


Metal-Organic Frameworks Can Photocatalytically Split Water-Why Not?
The opinion is provided about the stability and photocatalytic capability of metal-organic frameworks in photocatalytic overall water splitting.


Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues.
Four mexiletine analogues have been tested for their antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues and to assess calcium antagonist activity, in comparison with the parent compound mexiletine. All analogues showed from moderate to high antiarrhythmic activity. In particular, three of them (1b,c,e) were more active and potent than the reference drug, while exhibiting only modest or no negative inotropic and chronotropic effects and vasorelaxant activity, thus showing high selectivity of action. All compounds showed no cytotoxicity and 1b,c,d did not impair motor coordination. All in, these new analogues exhibit an interesting cardiovascular profile and deserve further investigation.


Effects of fasting and exogenous glucose delivery on cardiac tolerance to low-flow ischemia in adult and senescent rats.
Metabolic disorders due to changes in cytosolic glucose utilisation are suspected to be involved in the increased sensitivity of the aged myocardium to ischemia. This study presents the first direct measurement of glucose utilisation in hearts from senescent rats during low-flow ischemia under different conditions of substrate delivery and glycogen stores. Isolated hearts from young adult (4-months-old) and senescent (24-months-old) rats were subjected to 30 min coronary flow restriction (residual flow rate=2% of control flows). Experiments were performed using glucose-free or glucose-enriched (11 mmol/L) perfusion media. The effects of increased glycogen stores were assessed after 24-h fasting in both age groups. Ischemic contracture was measured via a left-ventricular balloon. Ageing increased ischemic contracture under both conditions of substrate delivery in fed rat hearts. The increase in ischemic tolerance induced by fasting in senescent rat hearts was less than that seen in young rat hearts. Moreover, fasting decreased glucose utilisation in hearts from young rats, an effect which was not found in hearts from old rats. Furthermore, myocardial glycogen utilisation was increased in all groups of aged rats compared with that of young adults, particularly under fasting conditions. It is concluded that fasting is less detrimental to the aged myocardium during low-flow ischemia than to the young myocardium because it does not further reduce exogenous glucose utilisation, and it stimulates glycogen consumption. Moreover, a reduction in exogenous glucose utilisation, which is only partly compensated for by increased glycogenolytic flux could be, at least in part, responsible for the increased ischemic contracture in hearts from old fed rats. Finally, our glucose-free experiments suggest that residual oxidative phosphorylation during low-flow ischemia might be less relevant in hearts from senescent rats than in those from young adults.


The transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agency-approved drug.
Transthyretin (TTR) is one of the many proteins that are known to misfold and aggregate (i.e., undergo amyloidogenesis) in vivo. The process of TTR amyloidogenesis causes nervous system and/or heart pathology. While several of these maladies are associated with mutations that destabilize the native TTR quaternary and/or tertiary structure, wild-type TTR amyloidogenesis also leads to the degeneration of postmitotic tissue. Over the past 20 years, much has been learned about the factors that influence the propensity of TTR to aggregate. This biophysical information led to the development of a therapeutic strategy, termed "kinetic stabilization," to prevent TTR amyloidogenesis. This strategy afforded the drug tafamidis which was recently approved by the European Medicines Agency for the treatment of TTR familial amyloid polyneuropathy, the most common familial TTR amyloid disease. Tafamidis is the first and currently the only medication approved to treat TTR familial amyloid polyneuropathy. Here we review the biophysical basis for the kinetic stabilization strategy and the structure-based drug design effort that led to this first-in-class pharmacologic agent.


Balancing Life and Work in a 2-Physician Relationship: Redefining the "Power Couple".
Balancing the requirements of work and personal life can be a struggle. It is challenging to do on your own, but even more difficult when partnered with someone with similar career goals. Often times, career choices are prioritized over personal ones, which puts stress on interpersonal relationships and time spent with our partner. Despite this struggle, it seems that 2-physician relationships are becoming more common-and they are succeeding. This article reviews the successes and challenges of the 2-physician relationship.


The relationship between adverse childhood experiences and depression: A cross-sectional survey with university students in Botswana.
Adverse childhood experiences (ACEs) are associated with severe life-long negative outcomes, including depression. Particularly in low- and middle-income countries, few studies have been conducted to assess the impact of ACEs. To assess the influence of ACEs on depression among young adults. Participants were students at a large university in Gaborone, Botswana. Using a cross-sectional design, we investigated the associations between ACEs and depression in young adults in Botswana (n = 392, mean age = 22.2, ± 2.5, 53.4% female). Bivariate correlation analyses, t-tests and analyses of variance (ANOVA) were performed to assess associations and compare ACEs at different levels of depression. A total of 73% (n = 287) reported one or more ACEs, whilst 15% (59) reported five or more ACEs. About 64% (38) of those who reported five or more ACEs were female respondents. Prevalence of specific ACEs ranged from 9.5% (child neglect) to 36.3% (separation and divorce). One in three respondents reported parental separation or divorce, psychological abuse and family dysfunction, whilst 19% (11% moderate and 8% severe) reported significant depressive symptoms. Adverse childhood experiences significantly predicted depression (β = 0.27, 95% confidence interval [CI]: 0.18, 0.37). Respondents at different levels of depression significantly differed on reporting ACEs (F (3, 389) = 11.43, p < 0.001). Adverse childhood experiences are highly prevalent and key determinants of depression in young adulthood. A multifaceted and cross-system intervention (e.g. schools, social work, psychological services, health services and law enforcement) is required to protect, prevent and treat survivors of childhood adversity.


Enhanced anti-cancer activity by localized delivery of curcumin form PVA/CNCs hydrogel membranes: Preparation and in vitro bioevaluation.
This study targets to develop curcumin-loaded polyvinyl alcohol/cellulose nanocrystals (PVA/CNCs) membrane as localized delivery system for breast/liver cancer. A novel strategy was developed for enhancing encapsulation capacity and maximizing therapeutic efficiency of curcumin-loaded PVA/CNCs membranes. Membranes were prepared by solution-casting method using citric acid as crosslinker. SEM revealed that PVA/CNCs ratio (80:20) was chosen as the optimum for loading curcumin. FT-IR indicated that, curcumin was incorporated into PVA/CNCs in amorphous-phase via intermolecular hydrogen bond between curcumin and membrane components. Curcumin showed biphasic-release through burst-release of 41% of curcumin during the first hour, followed by sustained-release of 70% and 94% during 24 h and 48 h, respectively. In vitro cytotoxicity of PVA/CNCs/Curcumin membrane exhibited a selective inhibition proliferation of breast and liver cancer cells in a concentration-dependent without any toxic effect on normal cells. At high concentration (8 mg/ml) of PVA/CNCs/Curcumin, reduced viability to 35% and 7% of MCF-7 and Huh-7 cells, respectively; meanwhile high HFB-4 normal cell viability ≥80% was investigated. Antimicrobial activity of PVA/CNCs/Curcumin was investigated by multi-drug-resistant strains, and MIC values. PVA/CNCs/Curcumin membranes with concentration (40 mg/ml) showed broad-spectrum antimicrobial activities, thus inhibited ~96-99% of microbial growth. PVA/CNCs/Curcumin membranes could be as promised anti-infective biomaterials for breast and liver cancer wound healing.


The Use of Electroencephalography as an Informative Tool in Assisting Early Clinical Management after Sport-Related Concussion: a Systematic Review.
Sport-related concussion (SRC) is managed primarily through serial clinical evaluations throughout recovery. However, studies suggest that clinical measures may not be suitable to detect subtle alterations in functioning and are limited by numerous internal and external factors. Electroencephalography (EEG) has been used for over eight decades to discern altered function following illnesses and injuries, including traumatic brain injury. This study evaluated the associations between EEG measures and clinical presentation within three-months following SRC. A systematic review of the literature was performed in Medline, Embase, PsycINFO, CINAHL and Web of Science databases following Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines, yielding a total of 13 peer-reviewed articles. Most studies showed low to moderate bias and moderate to high quality. The majority of the existing literature on the impact of concussion within the first 3 months post-injury suggests that individuals with concussion show altered brain function, with EEG abnormalities outlasting clinical dysfunction. Of all EEG biomarkers evaluated, P300 shows the most promise and should be explored further. Despite the relatively high quality of included articles, significant limitations are still present within this body of literature, including potential conflicts of interest and proprietary algorithms, making it difficult to draw strong and meaningful conclusions on the use of EEG in the early stages of SRC. Therefore, further exploration of the relationship between EEG measures and acute clinical presentation is warranted to determine if EEG provides additional benefits over current clinical assessments and is a feasible tool in clinical settings.


Metastatic carcinoma of the cervix in a patient with dermatomyositis.
A case of dermatomyositis occurring in a patient with metastatic carcinoma is reported. The epidemiology, incidence, and work-up of this disorder are discussed.


A radioimmunoassay for 3,5-diiodothyronine.
A radioimmunoassay for the measurement of 3,5-diiodothyronine (3,5-T2) using a 3H-labelled derivative of 3,5-T2 as tracer has been developed. The cross-reactivity of the antiserum was relatively high for T3 (3.1%) and low for T4 (less than 0.0015%). 3,5-T2 serum concentrations measured after fractional enrichment of 3,5-T2 were near or below the detection limit of 0.1 nmol/l in ten normal subjects and 0.38 nmol/l in five hyperthyroid patients. 3,5-T2 was also detected in thyroid tissue. The serum half-time of 3,5-T2 estimated after injection of 2 mg 3,5-T2 in three normal volunteers was 4.5 h.


Essential role of POLDIP2 in Tau aggregation and neurotoxicity via autophagy/proteasome inhibition.
In Alzheimer's disease and other tauopathy, abnormal Tau proteins form intracellular aggregates and Tau filaments. However, the mechanisms that regulate Tau aggregation are not fully understood. In this paper, we show that POLDIP2 is a novel regulator of Tau aggregation. From a cell-based screening using cDNA expression library, we isolated POLDIP2 which increased Tau aggregation. Expression of POLDIP2 was increased in neuronal cells by the multiple stresses, including Aβ, TNF-α and H2O2. Accordingly, ectopic expression of POLDIP2 enhanced the formation of Tau aggregates without affecting Tau phosphorylation, while down-regulation of POLDIP2 alleviated ROS-induced Tau aggregation. Interestingly, we found that POLDIP2 overexpression induced impairments of autophagy activity and partially proteasome activity and this activities were retained in DUF525 domain of POLDIP2. In a drosophila model of human tauopathy, knockdown of the drosophila POLDIP2 homolog, CG12162, attenuated rough eye phenotype induced by Tau overexpression. Further, the lifespan of neural-Tau(R406W) transgenic files were recovered by CG12162 knockdown. Together, these observations indicate that POLDIP2 plays a crucial role in Tau aggregation via the impairment of autophagy activity, providing insight into Tau aggregation in Tau pathology.


Neurological Dysfunction in Early Maturity of a Model for Niemann-Pick C1 Carrier Status.
Autosomal recessive inheritance of NPC1 with loss-of-function mutations underlies Niemann-Pick disease, type C1 (NP-C1), a lysosomal storage disorder with progressive neurodegeneration. It is uncertain from limited biochemical studies and patient case reports whether NPC1 haploinsufficiency can cause a partial NP-C1 phenotype in carriers. In the present study, we examined this possibility in heterozygotes of a natural loss-of-function mutant Npc1 mouse model. We found partial motor dysfunction and increased anxiety-like behavior in Npc1 (+/-) mice by 9 weeks of age. Relative to Npc1 (+/+) mice, Npc1 (+/-) mice failed to show neurodevelopmental improvements in motor coordination and balance on an accelerating Rotarod. In the open-field test, Npc1 (+/-) mice showed an intermediate phenotype in spontaneous locomotor activity compared with Npc1 (+/+) and Npc1 (-/-) mice, as well as decreased center tendency. Together with increased stride length under anxiogenic conditions on the DigiGait treadmill, these findings are consistent with heightened anxiety. Our findings indicate that pathogenic NPC1 allele carriers, who represent about 0.66 % of humans, could be vulnerable to motor and anxiety disorders.


Rhein: a potential biological therapeutic drug for intervertebral disc degeneration.
Intervertebral disc degeneration (IDD) is regarded as an important cause of low back pain, which continues to be a common disability. IDD is thought to involve sequential changes of intervertebral disc that lead to the reduction of disc cells and the extracellular matrix. In addition, inflammation is crucially involved in IDD. Currently, there is urgent need to develop biological therapies for IDD that can both relieve symptoms and directly reverse the process of degeneration. Rhein (RH) is an anthraquinone molecule with the abilities of enhancing the synthesis of matrix components and inhibiting inflammatory response. Recently, the metabolic precursor of RH called diacerein has been demonstrated to have significant effects on pain relief and function improvement in the treatment of osteoarthritis. Given the occurrence of matrix degeneration and involvement of inflammation in IDD, we propose that RH might be a promising biological therapeutic drug for IDD due to its bioactivities. In addition, we hypothesize that the underlying mechanisms might be that RH has the ability to diminish interleukin-1 (IL-1) induced apoptosis and inhibit IL-1 induced secretion of MMPs and aggrecanases.


Long-term local control rates of patients with adenoid cystic carcinoma of the head and neck managed by surgery and postoperative radiation.
To report long-term local control in patients with adenoid cystic cancer (ACC) of the head and neck managed by surgery and identify factors predictive for local failure. Single-institution retrospective cohort study. Eighty-seven patients who had surgery for ACC between 1985 and 2009 were identified. Patient, tumor, and treatment characteristics were recorded. Local recurrence-free survival (LRFS) was recorded by the Kaplan-Meier method. Predictors of local control were identified. The median age was 54 years. Seventy-two (83%) patients had perineural invasion, 61 (70%) had close/positive margins, and 58 (67%) had pT 1T2. Fifty-nine (68%) patients had postoperative radiation therapy (PORT). With a median follow-up of 85 months, the 10-year LRFS was 78.7%. There were 14 local recurrences. On multivariable analysis, pathological tumor (T)3T4 stage and no PORT were independent predictors for local failure. Patients with no PORT had a 13-fold increased risk of local failure compared to patients treated with PORT (P = 0.003) after adjusting for stage. After adjusting for T stage, patients who do not get PORT are more likely to have local recurrence. 4. Laryngoscope, 127:2265-2269, 2017.


Computer simulated modeling of biomolecular systems.
This paper describes the algorithm of a program used to simulate three dimensional models of molecules. In addition to open ended molecules the program also enables simulation of structures with constraints in the form of cyclic regions or fixed location of particular atoms. Several molecules can be handled in a single run and each molecule can have any number of contraints. Further, any number of conformations can be obtained for each constrained region. The program can be used for research in several areas of molecular biology, e.g., structure determination, conformational analysis and topographic comparisons.


Training in psychosomatic medicine and psychotherapy for medical doctors in China: A field report.
The high prevalence rates of mental disorders in China contrast a comparatively low care capacity from qualified trained medical doctors in the mental health field. The main objective of our cooperation project was to develop and implement advanced postgraduate training for medical doctors for their acquisition of knowledge, skills, and attitudes in the field of psychosomatic medicine and psychotherapy in China. Monitoring and evaluation as part of the advanced training in Beijing were conducted following the Kirkpatrick training approach using four levels of evaluation: reaction, learning, behavior and results. We performed a continuous course evaluation, assessed the respective learning goal attainment, conducted a pre-post evaluation of reasons and goals for participation in the training, and measured the treatment effects on the patient side. The implementation of training standards in the field of psychosomatic medicine and psychotherapy for medical doctors and the transfer of didactic knowledge and skills for Chinese lecturers were achieved. A total of 142 mainly medical doctors attended the 2-year training. Ten medical doctors were trained as future teachers. All learning goals were reached. The content and didactics of the curriculum were rated with an overall grade of 1.23 (1 = very good to 5 = very bad). The highest rated elements were patient life interviews, orientation on clinical practice and communication skills training. The achievement of learning objectives for each block (depression, anxiety disorders, somatic symptom disorder, coping with physical diseases) was rated between 1 and 2 (1 = very well achieved to 5 = not achieved) for all items from participants' perspectives. On the patient side (n = 415), emotional distress decreased and quality of life and the doctor-patient alliance improved significantly. Advanced training in psychosomatic medicine and psychotherapy was successfully implemented. The results of the evaluation show high participant satisfaction and the successful achievement of all learning objectives. A more detailed and extensive evaluation of the data, such as an analysis of the development of the participants as psychotherapists, is in preparation. The continuation of the training under Chinese guidance is guaranteed.


Subarachnoid hemorrhage due to late recurrence of a previously unruptured aneurysm after complete endovascular occlusion.
We present a case of subarachnoid hemorrhage attributed to rupture of an aneurysm 18 months after endovascular occlusion. The aneurysm was diagnosed after the patient had a seizure; however, there was no evidence of subarachnoid hemorrhage. Angiography at 6 months revealed a totally occluded aneurysm. This case illustrates that the long-term results of endovascular occlusion remain uncertain.


Radical prostatectomy versus high dose permanent prostate brachytherapy using iodine-125 seeds for patients with high risk prostate cancer: a matched cohort analysis.
To compare the biochemical outcomes reported after radical prostatectomy (RP) versus high dose permanent prostate brachytherapy (HDPPB) using iodine-125 seeds in the treatment of matched high risk prostate cancer (HiPCa). In this retrospective review, 55 HiPCa patients treated between March 2006 and August 2011, who underwent HDPPB using iodine-125 seeds combined with external beam radiation therapy (EBRT) or androgen deprivation therapy (ADT), were compared with 55 HiPCa patients who underwent RP. Patients were matched for age, prostate-specific antigen (PSA), clinical stage, and Gleason scores. The biochemical outcomes after HDPPB and RP were compared via Kaplan-Meier analysis. Of the 110 patients analyzed, the mean ages, PSA, and Gleason biopsy scores were similar between the two cohorts. Among patients who underwent HDPPB, 20 patients (36.4%) had received adjuvant EBRT. Of this subsample, most patients (98.2%) had received adjuvant ADT for 3 months. Among patients with RP, 20 patients (36.4%) had received adjuvant EBRT, whereas 28 patients had received adjuvant ADT. The mean implanted seed numbers were 92.8, the mean D90 was 218.7 Gy, and the mean V100 was 96.1% after HDPPB. With regard to oncological outcomes, biochemical disease-free survival rates were similar between the two cohorts (82.6 vs. 81.1%, p = 0.982). Urethrorectal fistula developed in one patient with HDPPB. RP and HDPPB, using iodine-125 seeds with combined treatment modalities, exhibited similar biochemical recurrence-free survival rates among HiPCa patients. Further prospective studies with greater sample sizes and longer follow-up periods are needed to validate these results.


Recent progress in biomedical applications of Pluronic (PF127): Pharmaceutical perspectives.
Most of the administered anti-cancer drugs are hydrophobic in nature and are known to have poor water solubility, short residence time, rapid clearance from the body and systemic side effects. Polymeric-based targeted particulate carrier system has shown to directly deliver the encapsulated anti-cancer drug to the desired site of action and prevent the interaction of encapsulated drug with the normal cells. Pluronic F127 (PF127) has been widely investigated for its broad-range of therodiagnostic applications in biomedical and pharmaceutical sciences, but rapid dissolution in the physiological fluids, short residence time, rapid clearance, and weak mechanical strength are the main shortcomings that are associated with PF127 and have recently been overcome by making various modifications in the structure of PF127 notably through preparation of PF127-based mixed polymeric micelles, PF127-conjugated nanoparticles and PF127-based hydrophobically modified thermogels. In this article, we have briefly discussed the recent studies that have been conducted on various anti-cancer drugs using PF127 as nano-carrier modified with other copolymers and/or conjugated with magnetic nanoparticles. The key findings of these studies demonstrated that the modified form of PF127 can significantly increase the stability of incorporated hydrophobic drugs with enhanced in vitro cytotoxicity and cellular uptake of anti-cancer drugs. Moreover, the modified form of PF127 has also shown its therapeutic potentials as therodiagnostics in various types of tumors and cancers. Hence, it can be concluded that the modified form of PF127 exhibits significant therodiagnostic effects with increased tumor-specific delivery of anti-cancer drugs having minimal toxic effects as compared to PF127 alone and/or other copolymers.


Initial Experience With Ultra High-Density Mapping of Human Right Atria.
Recently, an automatic, high-resolution mapping system has been presented to accurately and quickly identify right atrial geometry and activation patterns in animals, but human data are lacking. This study aims to assess the clinical feasibility and accuracy of high-density electroanatomical mapping of various RA arrhythmias. Electroanatomical maps of the RA (35 partial and 24 complete) were created in 23 patients using a novel mini-basket catheter with 64 electrodes and automatic electrogram annotation. Median acquisition time was 6:43 minutes (0:39-23:05 minutes) with shorter times for partial (4.03 ± 4.13 minutes) than for complete maps (9.41 ± 4.92 minutes). During mapping 3,236 (710-16,306) data points were automatically annotated without manual correction. Maps obtained during sinus rhythm created geometry consistent with CT imaging and demonstrated activation originating at the middle to superior crista terminalis, while maps during CS pacing showed right atrial activation beginning at the infero-septal region. Activation patterns were consistent with cavotricuspid isthmus-dependent atrial flutter (n = 4), complex reentry tachycardia (n = 1), or ectopic atrial tachycardia (n = 2). His bundle and fractionated potentials in the slow pathway region were automatically detected in all patients. Ablation of the cavotricuspid isthmus (n = 9), the atrio-ventricular node (n = 2), atrial ectopy (n = 2), and the slow pathway (n = 3) was successfully and safely performed. RA mapping with this automatic high-density mapping system is fast, feasible, and safe. It is possible to reproducibly identify propagation of atrial activation during sinus rhythm, various tachycardias, and also complex reentrant arrhythmias.


Identification of the variables associated with pain during transrectal ultrasonography-guided prostate biopsy in the era of periprostatic nerve block: the role of transrectal probe configuration.
To identify the different factors that are associated with pain perceived during transrectal ultrasonography (TRUS)-guided prostate biopsy (PBx), with special focus on the role of transrectal probe configuration. We analysed prospective data on 1114 patients undergoing TRUS-guided PBx at our institute from January 2007 to August 2010. Patients completed questionnaires based on a 10-point visual analogue pain scale related to the consecutive steps of PBx: probe insertion, application of periprostatic nerve block (PPNB) and the obtaining of PBx cores. The variables of interest were age, prostate volume, DRE findings, number of previous biopsies, probe type and the number of retrieved cores. All variables were correlated to pain scores using multivariate regression analysis. At the probe insertion step, end-fire probes were more painful than side-fire probes. The Siemens G50 with metal, short plastic and long plastic needle guides (Siemens, Munich, Germany) had higher pain scores than the B&K probe (Bruel & Kjaer Medical, Copenhagen, Denmark; P = 0.09, 0.008 and 0.003, respectively). For pain at the PPNB application step, all G50(TM) guide subtypes and the Sonoline Prima probe (Siemens) had higher pain scores than the B&K probe, but this only reached statistical significance for the G50(TM) probe with short plastic guide (P = 0.03). On obtaining PBx cores, all G50(TM) subtypes had higher pain scores when compared with the B&K probe (P = 0.59, 0.38 and 0.69, respectively). The probe design and needle guide affect pain during each step of TRUS-guided PBx. Both the B&K and Sonoline Prima probes caused less pain when compared with the G50(TM) probe, regardless of needle guide.


Application of acid-activated Bauxsol for wastewater treatment with high phosphate concentration: Characterization, adsorption optimization, and desorption behaviors.
Acid-activated Bauxsol was applied to treat wastewater with high phosphate concentration in a batch adsorption system in this paper. The effect of acid activation on the change of Bauxsol structure was systematically investigated. The mineralogical inhomogeneity and intensity of Bauxsol decreased after acid activation, and FeCl3·2H2O and Al(OH)3 became the dominant phases of acid-activated Bauxsol adsorption. Moreover, the BET surface area and total pore volume of Bauxsol increased after acid activation. Interaction of initial solution pH and adsorption temperature on phosphate adsorption onto acid-activated Bauxsol was investigated by using response surface methodology with central composite design. The maximum phosphate adsorption capacity of 192.94 mg g(-1) was achieved with an initial solution pH of 4.19 and an adsorption temperature of 52.18 °C, which increased by 7.61 times compared with that of Bauxsol (22.40 mg g(-1)), and was higher than other adsorbents. Furthermore, the desorption studies demonstrated that the acid-activated Bauxsol was successfully regenerated with 0.5 mol L(-1) HCl solution. The adsorption capacity and desorption efficiency of acid-activated Bauxsol maintained at 80.48% and 93.02% in the fifth adsorption-desorption cycle, respectively, suggesting that the acid-activated Bauxsol could be repeatedly used in wastewater treatment with high phosphate concentration.


Computer analysis of individual cataract surgery segments in the operating room.
Objective feedback is important for the continuous development of surgical skills. Motion tracking, which has previously been validated across an entire cataract procedure, can be a useful adjunct. We aimed to measure quantitative differences between junior and senior surgeons' performance in three distinct segments. We further explored whether automated analysis of trainee surgical videos through PhacoTracking could be aligned with metrics from the EyeSi virtual reality simulator, allowing focused improvement of these areas in a controlled environment. Prospective cohort analysis, comparing junior vs. senior surgeons' real-life performance in distinct segments of cataract surgery: continuous curvilinear capsulorhexis (CCC), phacoemulsification, and irrigation and aspiration (I&A). EyeSi metrics that could be aligned with motion tracking parameters were identified. Motion tracking parameters (instrument path length, number of movements and total time) were measured. t-test used between the two cohorts for each component to check for any significance (p < 0.05). A total of 120 segments from videos of 20 junior and 20 senior surgeons were analysed. Significant differences between junior and senior surgeons were found during CCC (path length p = 0.0004; number of movements p < 0.0001; time taken p < 0.0001), phacoemulsification (path length p < 0.0001; number of movements p < 0.0001; time taken p < 0.0001), and irrigation and aspiration (path length p = 0.006; number of movements p = 0.013; time taken p = 0.036). Individual segments of cataract surgery analysed using motion tracking appear to discriminate between junior and senior surgeons. Alignment of motion tracking and EyeSi parameters could enable independent, task specific, objective and quantitative feedback for each segment of surgery thus mirroring the widely utilised modular training.


Editorial Commentary: High Variability Exists Among Different Techniques for Measuring Glenoid Bone Loss.
Glenoid bone loss is a predominant factor in determining proper surgical management for glenohumeral instability. Precise measurements of glenoid (and humeral) bone defects are fundamental, and millimeters matter. Three-dimensional computed tomography scans may provide the highest interobserver reliability for making these measurements. Yet, because imprecision in the range of millimeters is observed with even the most precise glenoid bone loss measurement techniques, it could be a mistake to over-rely, let alone solely rely, on glenoid bone loss measurement as the primary determinant for selecting one surgical procedure over another. Surgeons must measure glenoid bone loss but also thoughtfully consider patient age, associated soft-tissue injuries, and activity level, including throwing and participation in collision sports. When choosing the proper surgical procedure for a shoulder instability patient, we should not focus on only one variably measured parameter but, instead, on a comprehensive assessment of the patient.


Brain stimulation to treat Internet addiction: A commentary.
In February, 2015, French television screened a report on Internet addiction (IA) in which an individual, identifying himself as cyberdependent, was offered treatment with repetitive Transcranial Magnetic Stimulation (rTMS), a Non-Invasive Brain Stimulation (NIBS) technique. Two issues deserve to be emphasized. Firstly, the concept of IA is not unanimously recognized by scientists and has raised a number of questions. Secondly, although the first results suggest that brain stimulation techniques could be a potential therapy for Substance Use Disorders (SUDs), no data are available on the therapeutic effects of rTMS on IA or even excessive Internet use. Currently, we cannot promote the use of rTMS for Internet detoxification because there is no evidence to prove its efficacy. Nevertheless, the similarities between SUDs and IA, and the results of NIBS on SUDs suggest that research can be done to examine the efficacy of NIBS techniques to treat Internet gaming disorder and other forms of IA.


Can virtual care reduce treatment burden in pediatric leukemia? A retrospective cost analysis.
We conducted a retrospective analysis to determine the potential reduction in treatment burden through the expansion of virtual care among children with leukemia (n = 152). Patients living in urban areas traveled median distances of 1555 km compared with 7536 km for patients living in rural areas (p < .05). For the latter group, a median reduction in travel distance of 3560 km (interquartile range [IQR], 2136-5787 km), travel time of 51 h (IQR, 26-78 h), and CO2 emissions of 623 kg (IQR, 374-1013 kg) was estimated, if every second visit was replaced by video consultations.


Lengthening osteotomy of the calcaneus and flexor digitorum longus tendon transfer in flexible flatfoot deformity improves talo-1st metatarsal-Index, clinical outcome and pedographic parameter.
Lengthening osteotomy of the calcaneus (LO) and flexor digitorum longus tendon (FDL) transfer to the navicular is one option for the treatment of flexible flatfoot deformity (FD). The aim of the study was to analyse the amount of correction and clinical outcome including pedographic assessment. In a prospective consecutive non-controlled clinical followup study, all patients with FD that were treated with LO and FDL from September 1st 2006 to August 31st, 2009 were included. Assessment was performed before surgery and at 2-year-followup including clinical examination (with staging of posterior tibialis insufficiency) weight bearing radiographs (Talo-1st metatarsal angles (TMT)), pedography (increased midfoot contact area and force) and Visual Analogue Scale Foot and Ankle (VAS FA). 112 feet in 102 patients were analysed (age, 57.6 (13-82), 42% male). In 12 feet (9%) wound healing delay without further surgical measures was registered. All patients achieved full weight bearing during the 7th postoperative week. Until followup, revision surgery was done in 3 patients (fusion calcaneocuboid joint (n=2), correction triple arthrodesis (n=1)). 101 feet (90%) completed 2-year-followup. TMT dorsoplantar/lateral/Index and VAS FA scores were increased, and posterior tibialis insufficiency stage, pedographic midfoot contact area and force percentage were decreased (each p<.05). All relevant parameters (stage of posterior tibialis insufficiency, TMT angles and Index, pedographic midfoot contact area and force percentage, VAS FA) were improved 2 years after LO and FDL transfer to the navicular in FD. The complication rate was low. This method allows safe and predictable correction.


Effects of H-7 (protein kinase inhibitor) and phorbol ester on aortic strips from spontaneously hypertensive rats.
We investigated the vascular responsiveness to vasoactive agents and the inhibition by H-7 (1-(5-isoquinoline-sulfonyl)-2-methylpiperazine), which inhibits cyclic nucleotide-dependent protein kinases and protein kinase C(PKC) equally potently in helically cut strips of thoracic aortas from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The susceptibility of norepinephrine (NE)- and angiotensin II (Ang II)-induced contractions to H-7 was significantly higher in the aortas from SHR than in those from WKY. H-7 decreased the contractile responses to KCl to a similar extent in both strains without affecting the high K(+)-stimulated Ca2+ influx. H-7 produced a shift to the right of the dose-response curve for the PKC activator, 12-o-tetradecanoylphorbol-13-acetate (TPA) in the case of SHR aortas, while no such shift was noted in tissues from WKY. Functional alterations in the PKC branch of the Ca2+ messenger system in vascular smooth muscle may play an important role in SHR during the sustained contraction.


Crystalline Anions Based on Classical N-Heterocyclic Carbenes.
Herein, the first stable anions K[SIPrBp ] (4 a-K) and K[IPrBp ] (4 b-K) (SIPrBp =BpC{N(Dipp)CH2 }2 , IPrBp =BpC{N(Dipp)CH}2 ; Bp=4-PhC6 H4 ; Dipp=2,6-iPr2 C6 H3 ) derived from classical N-heterocyclic carbenes (NHCs) (i.e. SIPr and IPr) have been isolated as violet crystalline solids. 4 a-K and 4 b-K are prepared by KC8 reduction of the neutral radicals [SIPrBp ] (3 a) and [IPrBp ] (3 b), respectively. The radicals 3 a and 3 b as well as [Me-IPrBp ] 3 c (Me-IPrBp =BpC{N(Dipp)CMe}2 ) are accessible as crystalline solids on treatment of the respective 1,3-imidazoli(ni)um bromides (SIPrBp )Br (2 a), (IPrBp )Br (2 b), and (Me-IPrBp )Br (2 c) with KC8 . The cyclic voltammograms of 2 a-2 c exhibit two one-electron reversible redox processes in -0.5 to -2.5 V region that correspond to the radicals 3 a-3 c and the anions (4 a-4 c)- . Computational calculations suggest a closed-shell singlet ground state for (4 a-4 c)- with the singlet-triplet energy gap of 17-24 kcal mol-1 .


A study to describe the health trajectory of patients with advanced renal disease who choose not to receive dialysis.
Some patients with end-stage renal failure (ESRF) are unlikely to benefit from dialysis and conservative management (CM) is offered as a positive alternative. Understanding the trajectory of illness by health care professionals may improve end-of-life care. We aimed to describe the trajectory of functional status within our CM population through a prospective, observational study using the objective Timed Up and Go (TUG) test and subjective Barthel Index (BI) and health-related quality of life (HRQoL) [EuroQol 5D-5L (EQ-5D-5L)] measurements and correlating them with demographic and laboratory data and with sentinel events. There was a significant increase in TUG scores over the 6 months prior to death {2.24 [95% confidence interval (CI) 1.16-4.32], P = 0.017} and a significant decrease in EQ-5D-5L [-0.19 (95% CI -0.33 to -0.06), P = 0.006]. The only significant associations with mortality were serum albumin [hazard ratio (HR) 0.81 (95% CI 0.67-0.97), P = 0.024] and male gender [HR 5.94 (95% CI 1.50-23.5), P = 0.011]. We have shown there is a significant decline in functional status in the last 6 months before death in the CM population. Of interest, there was a significant relationship of lower serum albumin with functional decline and risk of death. We hope that with improved insight into disease trajectories we can improve our ability to identify and respond to the changes in needs of these patients, facilitate complex and sensitive end-of-life discussions and improve end-of-life care.


Plasmodium vivax malaria: a re-emerging threat for temperate climate zones?
Plasmodium vivax was endemic in temperate areas in historic times up to the middle of last century. Temperate climate P. vivax has a long incubation time of up to 8-10 months, which partly explain how it can be endemic in temperate areas with a could winter. P. vivax disappeared from Europe within the last 40-60 years, and this change was not related to climatic changes. The surge of P. vivax in Northern Europe after the second world war was related to displacement of refugees and large movement of military personnel exposed to malaria. Lately P. vivax has been seen along the demilitarized zone in South Korea replication a high endemicity in North Korea. The potential of transmission of P. vivax still exist in temperate zones, but reintroduction in a larger scale of P. vivax to areas without present transmission require large population movements of P. vivax infected people. The highest threat at present is refugees from P. vivax endemic North Korea entering China and South Korea in large numbers.


Perioperative anticoagulation for children with prosthetic mechanical valves.
The insertion of a mechanical heart valve predisposes to thrombosis and embolism, and for this reason, individuals with mechanical valves who undergo dental/surgical procedures must take special precautions. In this article, we illustrate a protocol for anticoagulation during such procedures in individuals with mechanical valves.


Cuticular property affects the insecticidal synergy of major constituents in thyme oil against houseflies, Musca domestica.
Plant essential oils are intricate blends comprising predominantly of monoterpenes and some sesquiterpenes. These oils display diverse bioactivities against targeted organisms, often arising from complex interactions among their constituents, which may demonstrate synergistic or antagonistic effects. Despite their wide use as botanical insecticides, the mechanisms behind these interactions and their effects on bioactivity are poorly understood. This study investigated the synergistic interaction of thymol and p-cymene, two major constituents of Thymus vulgaris essential oil, on the larvae and adults of the housefly, Musca domestica. The results showed that p-cymene synergized the insecticidal activity of thymol in adult houseflies, but not in larvae. GC-MS analyses and bioassays indicated the increased cuticular penetration of thymol by p-cymene was the mechanism of synergy, which was observed only in the adults. Two potential routes were proposed: the expansion of the wetting area, or the disruption of cuticular integrity through dissolving the wax layer. The sequential application and large-volume treatment bioassay results suggested that the former was the more likely mechanism. Also, the hydrophobicity of the cuticle seemed critical for this stage-specific synergy. Wax-devoid adults failed to show synergistic toxicity, whereas artificially wax-coated larvae gained a synergistic effect. Overall, the findings provide insights into the synergistic mechanism of insecticidal activity of plant essential oils and suggest potential applications in developing effective strategies using penetration-enhancing synergists.


Clinical application of computed tomography to thyroid disease.
CT examinations were carried out in 62 patients with various thyroid disorders, 42 patients with thyroid nodules, 12 with diffuse abnormality and 8 of others. Evaluation was made whether CT could provide more information compared with other techniques. Cystic thyroid nodules could be differentiated from solid nodules with a reasonably high degree of accuracy. Uncalcified thyroid carcinoma was noticed as an ill-defined nodule with irregular wall, grossly the same in density with the muscle in plain CT, and not opacified by contrast material. CT has the ability to define the nature of the thyroid nodules better than other nontraumatic diagnostic modalities.


Phytochemical analysis of Origanum majorana L. extract and investigation of its antioxidant, anti-inflammatory and immunomodulatory effects against experimentally induced colitis downregulating Th17 cells.
Origanum majorana L. is a member of the Lamiaceae family and is commonly used in Egyptian cuisine as a seasoning and flavor enhancer. It is also recognized as a well-known traditional medicine in Egypt and is widely used for treating abdominal colic due to its antispasmodic properties. However, the protective effects of Origanum majorana L. against ulcerative colitis and its underlying mechanisms remain unclear. This study aimed to identify the biologically active components present in methanol extracts of Origanum majorana L. using gas chromatography/mass spectrometry (GC/MS). Additionally, it aimed to investigate the therapeutic effects of these extracts on acetic acid-induced ulcerative colitis and elucidate the potential mechanisms involved. We conducted a GC-MS analysis of the methanolic extract obtained from Origanum majorana L. Thirty-two male rats were included in the study and divided into four experimental groups, with eight rats in each group: sham, UC, UC + O. majorana, and UC sulfasalazine. After euthanizing the rats, colon tissue samples were collected for gross and microscopic examinations, assessment of oxidative stress, and molecular evaluation. GC-MS analysis identified 15 components in the extracts. Pretreatment with O. majorana L. extract and sulfasalazine significantly improved the disease activity index (DAI) and resulted in notable improvements in macroscopic and microscopic colon findings. Additionally, both treatments demonstrated preventive effects against colonic oxidative damage by reducing the levels of malondialdehyde (MDA) and increasing the levels of the antioxidant systems superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), which operate through the Nrf2/HO-1 signaling pathway. Moreover, these treatments downregulated the colonic inflammatory cascade by inhibiting NFκB, TNFα, IL-1β, IL6, IL23, IL17, COX-2, and iNOS, subsequently leading to downregulation of the JAK2/STAT3 signaling pathway and a decrease in the Th17 cell response. Furthermore, a reduction in the number of apoptotic epithelial cells that expressed caspase-3 was observed. pretreatment with O. majorana L. extract significantly ameliorated acetic acid-induced ulcerative colitis. This effect could be attributed to the protective, antioxidant, anti-inflammatory, and anti-apoptotic properties of the extract.


How Is the History of Early Traumatic Exposure Associated With the Psychopathological Outcomes of COVID-19 Related Lockdown and Subsequent Re-opening in People With Eating Disorders?
The negative impact of COVID-19 pandemic on people with Eating Disorders (EDs) has been documented. The aim of this study was to evaluate whether a history of traumatic experiences during childhood or adolescence was associated with a higher degree of psychopathological worsening during COVID-19 related lockdown and in the following re-opening period in this group of people. People with EDs undergoing a specialist ED treatment in different Italian services before the spreading of COVID-19 pandemic (n = 312) filled in an online survey to retrospectively evaluate ED specific and general psychopathology changes after COVID-19 quarantine. Based on the presence of self-reported traumatic experiences, the participants were split into three groups: patients with EDs and no traumatic experiences, patients with EDs and childhood traumatic experiences, patients with EDs and adolescent traumatic experiences. Both people with or without early traumatic experiences reported retrospectively a worsening of general and ED-specific psychopathology during the COVID 19-induced lockdown and in the following re-opening period. Compared to ED participants without early traumatic experiences, those with a self-reported history of early traumatic experiences reported heightened anxious and post-traumatic stress symptoms, ineffectiveness, body dissatisfaction, and purging behaviors. These differences were seen before COVID-19 related restrictions as well as during the lockdown period and after the easing of COVID-19 related restrictions. In line with the "maltreated ecophenotype" theory, these results may suggest a clinical vulnerability of maltreated people with EDs leading to a greater severity in both general and ED-specific symptomatology experienced during the exposure to the COVID-19 pandemic.


Incidence and predictors of valgus tibiotalar tilt after progressive collapsing foot deformity reconstruction using subtalar fusion with concomitant procedures.
Development of valgus tibiotalar tilt is a significant complication after subtalar fusion for progressive collapsing foot deformity (PCFD) correction. However, its incidence and etiologic factors have not been extensively studied. The purpose of this study was to define the incidence of valgus tibiotalar tilt after subtalar fusion for PCFD reconstruction, and to determine predictors of this complication. This study included 59 patients who underwent PCFD reconstruction with subtalar fusion. Patients with tibiotalar tilt prior to surgery were excluded. On standard weightbearing radiographs, the talonavicular coverage angle, talo-1st metatarsal angle, calcaneal pitch, hindfoot moment arm (HMA), and medial distal tibial angle were measured. Weightbearing computed tomography (WBCT) was used to determine the presence of lateral bony impingement. A radiologist evaluated the superficial and deep deltoid ligaments using magnetic resonance imaging (MRI). Univariate regression analysis was used to identify the factors associated with development of postoperative valgus tibiotalar tilt, defined as tilt > 2 degrees. Seventeen patients (28.8%) developed postoperative valgus tibiotalar tilt at a mean of 7.7 (range 2-31) months. Eight (47.1%) of these patients developed valgus tibiotalar tilt within 3 months. Univariate logistic regression demonstrated association between preoperative HMA and postoperative valgus tibiotalar tilt (odds ratio 1.06, P = 0.026), with a 6% increase in risk per millimeter of increased HMA. Deltoid ligament status and concomitant procedures on other joints did not correlate with postoperative valgus tilt. Our findings indicate that surgeons should be cognizant of patients with a greater degree of preoperative hindfoot valgus and their propensity to develop a valgus ankle deformity. Additionally, our relatively high incidence of valgus tibiotalar tilt suggests that weightbearing ankle radiographs should be included in the initial and subsequent follow-up of PCFD patients with hindfoot valgus treated with subtalar fusion.


Survival and Prognosis of Patients with Pilocytic Astrocytoma: A Single-Center Study.
Pilocytic astrocytoma (PA) is a brain tumor that is relatively more common in children and young adults. We retrospectively reviewed the medical records of patients with PA treated at a single center between 1988 and 2018. We included 31 subjects with PA. The median age at diagnosis was 13.4 years, and the median follow-up duration was 9.9 years. The total PA group had a 10-year disease-specific survival (DSS) rate of 92.6% [95% confidence interval (CI), 82.6-100] and 10-year progression-free survival (PFS) rate of 52.8% (95% CI, 32.0-73.6). In patients aged <20 years, tumors were more likely to be located in sites in which gross total tumor resection (GTR) was impossible. No statistically significant difference in 10-year DSS was found between the GTR (100%) and non-GTR (89.7%; 95% CI, 76.2-100; p=0.374) groups. However, a statistically significant difference in 10-year PFS was found between the GTR (100%) and non-GTR groups (30.7%; 95% CI, 8.6-52.8; p=0.012). In the non-GTR group, no statistically significant difference in 10-year DSS was found between the patients who received immediate additional chemotherapy and/or radiotherapy (Add-Tx group, 92.9%; 95% CI, 79.4-100) and the non-Add-Tx group (83.3%; 95% CI, 53.5-100; p=0.577). No statistically significant difference in 10-year PFS was found between the Add-Tx group (28.9%; 95% CI, 1.7-56.1) and non-Add-Tx group (33.3%; 95% CI, 0-70.9; p=0.706). The PFS of the patients with PA in our study depended only on the degree of surgical excision associated with tumor location. This study is limited by its small number of patients and retrospective nature. A multicenter and prospective study is necessary to confirm these findings.


Parents' Perception of Fall Risk and Incidence of Falls in the Pediatric Ambulatory Environment.
To identify the parents' perspective of fall incidence and risks in the pediatric ambulatory environment. A prospective descriptive correlational study was conducted in two large quaternary pediatric hospitals. Parents who accompanied their children to the clinic appointment were surveyed about falls their child experienced while at the clinic. Parent reported falls were compared to those reported in adverse event reporting systems (AERS) for the same period. Data from 2327 completed parent surveys were analyzed. Parents reported 48 children fell and 139 falls. Only three falls were recorded in the AERS. Stepwise logistic regression was used to identify predictors of falls and a nomogram was created from the final model to facilitate patient fall risk screening. Three predictors of falls were identified: children under the age of five, children described by their parents as falling more at home than other children of the same age, and children who had a medical condition that impacts their ability to walk. A nomogram is provided to estimate the probability of falling for patients under 18 years of age in the ambulatory environment. Parents may provide more reliable data regarding the incidence and risk factors for falls in the ambulatory environment than AERS, and it is possible to predict the probability of a fall given information from the parents. Knowing who is at risk for falls creates opportunities for organizations to modify clinic procedures, train staff, and create physical environments that promote increased patient safety.


Hand hygiene improvement or antibiotic restriction to control the household transmission of extended-spectrum β-lactamase-producing Escherichia coli: a mathematical modelling study.
The best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking. We developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon. The probability of ESBL-EC transmission depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC transmission was 5.3% (95% CI 5.0-5.6) or 6.6% (6.3-6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of transmission varied from 61.4% (60.9-62.0) to 68.8% (68.3-69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33-62%. Antibiotic restriction by 50% reduced the transmission by 2-6%. The transmission of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC.


The videoendoscopic swallowing study: an alternative and partner to the videofluoroscopic swallowing study.
A new, physical examination-based videoendoscopic method of evaluation can enhance considerably the understanding and efficiency of clinicians working with patients with swallowing difficulties. Using the fiberoptic nasolaryngoscope, evaluation of structure and function of palate, pharynx, and larynx, along with sensation of the laryngopharynx, is carried out. Next, patients' swallowing capabilities are assessed as they ingest various food consistencies. This method, formerly called videoendoscopic evaluation of dysphagia (VEED), but perhaps more appropriately termed videoendoscopic swallowing study (VESS) has particular value for patients who cannot undergo the videofluoroscopic swallowing study (VFSS)--for example, because they are bedfast--or those whose swallowing function is changing so rapidly (after a stroke or surgery) as to call for frequent reassessments. This technique is often useful during the initial consultation with new patients complaining of dysphagia, as a "stand alone" method of diagnosis and management. Less frequently, VESS findings, along with patient history, will indicate when VFSS should also be obtained. VESS will orient the examiner to the nature and severity of the problem even in this latter circumstance. In follow-up circumstances, VESS is generally more useful than the VFSS. Case presentations are utilized to illustrate the usefulness of VESS as compared to VFSS.


Laryngeal Cyst in Children : A Retrospective Analysis.
Aim: To study the presentation, management and outcome of laryngeal cysts in children. Materials and methods: This is a retrospective observational study of children with Laryngeal cysts who were managed in the Department of Paediatric Surgery between April 2015 to Jan 2022. Observations and Results: Eight children with laryngeal cysts were included, 5 were girls. Age ranged from 3 days to 10 years (median 5 months). Weight ranged from 3kg to 40kg (median 6.3 kg). All presented with stridor. Three children had co-morbid conditions, one each with Leucocyte adhesion deficiency type -1, atrial septal defect & PHACES syndrome. Two children had severe respiratory distress and required tracheostomy at presentation. All children underwent MLB. The cysts were 2 subglottic cysts (one inflammatory cyst) and 6 vallecular cyst. Five underwent endoscopic excision of cysts, 1 underwent excision with lateral cervical approach, 1 underwent endoscopic de-roofing of cyst and airway reconstruction with anterior costal cartilage graft (associated Sub glottis stenosis). Conclusion: Laryngeal cysts are a rare cause of stridor in children. MLB is the best diagnostic tool. Treatment with excision / deroofing of the cyst endoscopically, is safe and effective in paediatric age group. The online version contains supplementary material available at 10.1007/s12070-023-03495-w.


Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs.
The efficacy of lipid-encapsulated, chemically modified short interfering RNA (siRNA) targeted to hepatitis B virus (HBV) was examined in an in vivo mouse model of HBV replication. Stabilized siRNA targeted to the HBV RNA was incorporated into a specialized liposome to form a stable nucleic-acid-lipid particle (SNALP) and administered by intravenous injection into mice carrying replicating HBV. The improved efficacy of siRNA-SNALP compared to unformulated siRNA correlates with a longer half-life in plasma and liver. Three daily intravenous injections of 3 mg/kg/day reduced serum HBV DNA >1.0 log(10). The reduction in HBV DNA was specific, dose-dependent and lasted for up to 7 d after dosing. Furthermore, reductions were seen in serum HBV DNA for up to 6 weeks with weekly dosing. The advances demonstrated here, including persistence of in vivo activity, use of lower doses and reduced dosing frequency are important steps in making siRNA a clinically viable therapeutic approach.


The human active breakpoint cluster region-related gene encodes a brain protein with homology to guanine nucleotide exchange proteins and GTPase-activating proteins.
GTPase-activating proteins (GAPs) modulate the activity of the ras superfamily of proteins by converting active GTP-bound to inactive GDP-bound p21s. Employing a novel GAP overlay assay (Manser, E., Leung, T., Monfries, C., Teo, M., Hall, C., and Lim, L. (1992) J. Biol. Chem. 267, 16025-16028), we demonstrated a diversity of proteins with GAP activities in different tissues. Using a polymerase chain reaction strategy exploiting conserved residues in the GAP domains of n-chimaerin and the product of the breakpoint cluster region gene (BCR), we isolated a human brain 5.3-kilobase cDNA containing a 486-base pair region with complete identity to a previously reported active BCR-related (ABR) gene sequence on human chromosome 17. The brain cDNA encoded a 98-kDa protein (ABR) resembling BCR (68% identity), containing both the oncogene dbl-related domain at the N terminus and the GAP domain at the C terminus; however, it lacks the N-terminal BCR protein kinase domain. The ABR GAP domain expressed as an Escherichia coli fusion protein was active against Rac1 and Cdc42 of the rho subfamily. The ABR mRNA is highly enriched in the brain. ABR probably corresponds to the brain-enriched 100-kDa GAP for Rac and Cdc42Hs previously detected. The relationship of ABR to Miller-Dieker syndrome, a neurological disorder co-mapping to 17p13.3, is discussed.


Differences in systemic inflammation between cigarette and biomass smoke-induced COPD.
It is known that biomarkers of systemic inflammation are raised in COPD caused by tobacco (T-COPD) compared with healthy controls, but there is less information on the inflammatory status of subjects with COPD caused by biomass smoke (B-COPD). In addition, the possible (if any) differences in inflammation between both types of the disease are still not well known. The aim of this study was to assess the inflammatory profile in B-COPD and T-COPD. A total of 20 subjects (15 men and five women) with T-COPD were matched one to one for sex, age and forced expiratory volume in 1 s (FEV1) to 20 B-COPD patients. In all, 20 sex-matched healthy subjects with normal lung function without smoking history or biomass exposure were included as controls. The following biomarkers were measured: exhaled nitric oxide, serum IL-6, IL-8, IL-5, IL-13, periostin, surfactant protein-P, TNF-α, IgE, erythrocyte sedimentation rate, C-reactive protein and fibrinogen. Complete blood count was also obtained. The age of the subjects was 70.2±7.9 years and FEV1% was 56.2%±14.6%. Most inflammatory biomarkers were higher in both types of COPD than in healthy controls. IL-6, IL-8 and IL-5 were significantly higher in T-COPD than in B-COPD, without other significant differences. Both types of COPD are associated with high levels of systemic inflammation biomarkers. T-COPD patients have a higher systemic inflammatory status than the patients with B-COPD.


Langerhans cell histiocytosis of the clavicle: a case report.
A case of Langerhans cell histiocytosis in a 47-year-old male presenting as an aggressive appearing lesion of the clavicle is reported. It illustrates the difficulties of the radiological diagnosis of a solitary bone lesion.


Bacterial recolonization of the skin and wound contamination during cardiac surgery: a randomized controlled trial of the use of plastic adhesive drape compared with bare skin.
Sternal wound infection after cardiac surgery is a serious complication. Various perioperative strategies, including plastic adhesive drapes, are used to reduce bacterial contamination of surgical wounds. To compare plastic adhesive drape to bare skin regarding bacterial growth in wound and time to recolonization of the adjacent skin intraoperatively, in cardiac surgery patients. This single-blinded randomized controlled trial (May 2010 to May 2011) included 140 patients scheduled for cardiac surgery via median sternotomy. The patients were randomly allocated to the adhesive drape (chest covered with plastic adhesive drape) or bare skin group. Bacterial samples were taken preoperatively and intraoperatively every hour during surgery until skin closure. Disinfection with 0.5% chlorhexidine solution in 70% alcohol decreased coagulase-negative staphylococci (CoNS), while the proportion colonized with Propionibacterium acnes was not significantly reduced and was still present in more than 50% of skin samples. P. acnes was significantly more common in men than in women. Progressive bacterial recolonization of the skin occurred within 2-3 h. At 120 min there were significantly more positive cultures in the adhesive drape group versus bare skin group for P. acnes (63% vs 44%; P = 0.034) and for CoNS (45% vs 24%; P = 0.013). The only statistically significant difference in bacterial growth in the surgical wound was higher proportion of CoNS at the end of surgery in the adhesive drape group (14.7% vs 4.4%; P = 0.044). Plastic adhesive drape does not reduce bacterial recolonization. P. acnes colonized men more frequently, and was not decreased by disinfection with chlorhexidine solution in alcohol.


Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases.
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility of CDK8/19 inhibitors. We discovered two series of potent chemical probes with high selectivity for CDK8/19. Despite pharmacodynamic evidence for robust on-target activity, the compounds exhibited modest, though significant, efficacy against human tumor lines and patient-derived xenografts. Altered gene expression was consistent with CDK8/19 inhibition, including profiles associated with super-enhancers, immune and inflammatory responses and stem cell function. In a mouse model expressing oncogenic beta-catenin, treatment shifted cells within hyperplastic intestinal crypts from a stem cell to a transit amplifying phenotype. In two species, neither probe was tolerated at therapeutically-relevant exposures. The complex nature of the toxicity observed with two structurally-differentiated chemical series is consistent with on-target effects posing significant challenges to the clinical development of CDK8/19 inhibitors.


Chronic social isolation enhances reproduction in the monogamous prairie vole (Microtus ochrogaster).
Chronic stressors are generally considered to disrupt reproduction and inhibit mating. Here we test the hypothesis that a chronic stressor, specifically social isolation, can facilitate adaptive changes that enhance/accelerate reproductive effort. In general, monogamous species display high levels of prosociality, delayed sexual maturation, and greater parental investment in fewer, higher quality offspring compared with closely related polygynous species. We predicted that chronic social isolation would promote behavioral and neurochemical patterns in prairie voles associated with polygyny. Male and female prairie voles were isolated for four weeks and changes in mating behavior, alloparental care, estrogen receptor (ER) α expression and tyrosine hydroxylase (TH) expression in brain regions regulating sociosexual behavior were examined. In males, isolation accelerated copulation, increased ERα in the medial amygdala (MEApd) and bed nucleus of the stria terminalis (BSTpm), and reduced TH expression in the MEApd and BSTpm, but had no effect on alloparental behavior. In females, isolation resulted in more rapid estrus induction and reduced TH expression in the MEApd and BSTpm, but had no effect on estradiol sensitivity or ERα expression. The results support the hypothesis that ERα expression in the MEApd and BSTpm is a critical determinant of male copulatory behavior and/or mating system. The lack of change in alloparental behavior suggests that changes in prosocial behavior are selective and regulated by different mechanisms. The results also suggest that TH in the MEApd and BSTpm may play a critical role in determining mating behavior in both sexes.


Tyrosine residues of the extrinsic 23 kDa protein are important for its interaction with spinach PSII membranes.
The 1, 4, and 8 tyrosine (Tyr) residues on the PSII extrinsic 23 kDa protein were modified with 5, 10 or 40 mM N-acetylimidazole (NAI) respectively. The amount of rebound NAI-modified extrinsic 23 kDa protein was 98%, 80%, and 5% of that in the unmodified protein, respectively. These results indicate that the Tyr residues are absolutely essential to reconstitution ability. Further, the fluorescence and circular dichroism spectra among native and NAI-modified extrinsic 23 kDa proteins were similar, suggesting that the modification by NAI did not markedly influence the basic secondary structure of the native conformation. Thus, we have concluded that the tyrosine residues in the extrinsic 23 kDa protein are important for interaction with PSII membranes. In addition, we found that the structure of the extrinsic 23 kDa protein is stable in suspension (pH 4-9 or Tm 25-55 degrees C).


Lymphatic metastasis of tumour; persistent transport of cells.
A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumour cells was continuous over periods up to 90 min and ranged from 10(2)-10(5) cells/min.


Genital Infection With Herpes Simplex Virus Type 1 and Type 2 in Valencia, Spain: A Retrospective Observational Study.
The epidemiology of genital herpes has changed in recent years with an increase in the incidence of herpes simplex virus type 1 (HSV-1) infection. The aim of this study was to analyze the clinical and epidemiological characteristics of patients diagnosed with genital herpes. A retrospective observational study was designed. All patients diagnosed with genital herpes between January 2016 and January 2019 in a Sexually Transmitted Infections Unit (ITS) in Valencia, Spain, were included. We identified 895 STI diagnoses. Of these, 126 (14%) were genital herpes; 68 (54%) of these cases were in women and 58 (46%) in men. Diagnosis was confirmed by molecular detection of HSV DNA in 110 cases (87.3%). Of these, 52 were cases of HSV-1 infection (47.3%) and 58 were HSV-2 infection (52.7%). HSV-2 was more common in men (69.5%), while HSV-1 was more common in women (59.3%). In the subgroup of women, mean age at diagnosis was 26 years for HSV-1 and 34 years for HSV-2 (P=.015). Recurrent genital herpes rates were 13% for HSV-1 and 40% for HSV-2. There has been an increase in the number of cases of genital herpes caused by HSV-1 in our setting, with young women in particular being affected. This has important prognostic implications because genital herpes caused by HSV-1 is less likely to recur.


Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study.
To determine whether the use of glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, separately, is associated with a decreased risk of exacerbations of chronic obstructive pulmonary disease among patients with chronic obstructive pulmonary disease and type 2 diabetes. Population based cohort study using an active comparator, new user design. The United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases. Three active comparator, new user cohorts of patients starting the study drugs (GLP-1 receptor agonists, DPP-4 inhibitors, or SGLT-2 inhibitors) or sulfonylureas with a history of chronic obstructive pulmonary disease. The first cohort included 1252 patients starting GLP-1 receptor agonists and 14 259 starting sulfonylureas, the second cohort included 8731 patients starting DPP-4 inhibitors and 18 204 starting sulfonylureas, and the third cohort included 2956 patients starting SGLT-2 inhibitors and 10 841 starting sulfonylureas. Cox proportional hazards models with propensity score fine stratification weighting were fitted to estimate hazard ratios and 95% confidence intervals of severe exacerbation of chronic obstructive pulmonary disease (defined as hospital admission for chronic obstructive pulmonary disease), separately for GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Whether these drugs were associated with a decreased risk of moderate exacerbation (defined as a co-prescription of an oral corticosteroid and an antibiotic along with an outpatient diagnosis of acute chronic obstructive pulmonary disease exacerbation on the same day) was also assessed. Compared with sulfonylureas, GLP-1 receptor agonists were associated with a 30% decreased risk of severe exacerbation (3.5 v 5.0 events per 100 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and moderate exacerbation (0.63, 0.43 to 0.94). DPP-4 inhibitors were associated with a modestly decreased incidence of severe exacerbation (4.6 v. 5.1 events per 100 person years; hazard ratio 0.91, 0.82 to 1.02) and moderate exacerbation (0.93, 0.82 to 1.07), with confidence intervals including the null value. Finally, SGLT-2 inhibitors were associated with a 38% decreased risk of severe exacerbation (2.4 v 3.9 events per 100 person years; hazard ratio 0.62, 0.48 to 0.81) but not moderate exacerbation (1.02, 0.83 to 1.27). In this population based study, GLP-1 receptor agonists and SGLT-2 inhibitors were associated with a reduced risk of severe exacerbations compared with sulfonylureas in patients with chronic obstructive pulmonary disease and type 2 diabetes. DPP-4 inhibitors were not clearly associated with a decreased risk of chronic obstructive pulmonary disease exacerbations.


The development of parvalbumin and calbindin-D28k immunoreactive interneurons in kitten visual cortical areas.
Calbindin-D and parvalbumin are calcium binding proteins which are found in non-overlapping subpopulations of GABA-ergic interneurons in mammalian neocortex. We studied the development of these calcium-binding proteins in interneurons of cat striate and extrastriate cortical areas which have differing patterns of connectivity and follow different developmental timetables. We examined primary visual areas 17 and 18, secondary visual area 19, medial lateral suprasylvian and lateral suprasylvian areas (MLS and LLS) and association areas 7 and the splenial visual area from the day of birth (P0) through P101. Parvalbumin-immunoreactive (ir) interneurons followed the inside-out pattern of maturation of cortical laminae. They were located only in infragranular layers at the earliest ages and were not observed in the overlying cortical plate. At 3 weeks of age, when cortical lamination is mature, parvalbumin stained cells were found in all cortical layers except layer I. The number of stained secondary and tertiary dendrites in the parvalbumin-ir interneuronal population decreased with age. This change was associated with a shift in the molecular weight of parvalbumin detected on Western blots. During the first postnatal week, the area 17/18 border contained more parvalbumin-ir neurons than other visual areas. The developmental pattern of calbindin staining differed considerably from the parvalbumin staining pattern. Very few calbindin-ir interneurons were seen in area 17 during the first 2 weeks of life. In lateral cortical areas, calbindin-ir neurons were located in cortical plate, infragranular layers of cortex and white matter/subplate. Calbindin-ir neurons increased in supragranular layers of secondary cortical areas by P7 and in area 17 by P20. In the mature cortex, the calbindin staining pattern was bilaminar, with a dense band of calbindin-ir cells in layer II and a second band in layers V-VI. There was no difference in the distribution of calbindin-ir neurons among visual areas at maturity.


Disparities in access to specialty care and emergency department use after hospital discharge to a skilled nursing facility.
Patterns in access to specialists among patients in skilled nursing facilities (SNFs) have not been previously described. To measure access to outpatient specialty follow-up and subsequent emergency department (ED) visits by patient characteristics, including race/ethnicity and those who received specialty care during the hospitalization that preceded the SNF stay. This retrospective cohort study used the minimum data set and 100% Medicare fee-for-service claims for beneficiaries admitted to an SNF between 2012 and 2014. Hospital stays for surgical procedures were excluded. The associations between ED visits, follow-up, and race/ethnicity were measured using logistic and linear regression, adjusting for patient demographic and clinical characteristics. The sample included 1,117,632 hospitalizations by Medicare beneficiaries ≥65 with a consult by a medical subspecialist followed by discharge to SNF. Of the sample, 85.4% were non-Hispanic White (NHW) and 14.6% were Black, indigenous, and people of color (BIPOC), according to Medicare beneficiary records. During the SNF stay, BIPOC patients had lower odds of specialty follow-up compared to NHW patients (odds ratio [OR]: 0.96, 95% confidence intervals [CI]: 0.94-0.99, p = .004). BIPOC patients had higher rates of ED visits compared to NHW patients (with follow-up: 24.1% vs. 23.4%, and without follow-up: 27.4% vs. 25.9%, p < .001). Lack of follow-up was associated with a 0.8 percentage point difference in ED visits between BIPOC and NHW patients (95% CI: 0.3-1.3, p = .003). There is a racial/ethnic disparity in subspecialty follow-up after hospital discharge to SNF that is associated with a higher rate of subsequent ED visits by BIPOC patients.


CCDC7 Activates Interleukin-6 and Vascular Endothelial Growth Factor to Promote Proliferation via the JAK-STAT3 Pathway in Cervical Cancer Cells [Retraction].
[This retracts the article DOI: 10.2147/OTT.S244663.].


A t(4;11)(q21;p15) in a case of T-cell lymphoma and a case of acute myelogenous leukemia.
The translocation (4;11)(q21;p15) has been observed in acute lymphoblastic as well as acute myeloid leukemias (ALL and AML, respectively). We report the first case of T-cell lymphoma with t(4;11)(q21;p15) and a case of AML. The clinical history of and cytogenetics in the latter is suggestive of a secondary leukemia; his karyotype revealed emergence of a t(3;11)(q21;q13) in addition to the t(4;11). Previously reported cases with t(4;11)(q21;p15) are reviewed, clinical and morphological characteristics of cases with t(4;11)(q21;q23) and t(4;11)(q21;p15) are compared, and chromosome abnormalities involving the NUP98 gene in hematologic malignant disorders are reviewed.


Optimal thyrotropin level: normal ranges and reference intervals are not equivalent.
This paper marshals arguments in support of a narrower, optimal or true normal range for thyrotropin (TSH) of 0.4 to 2.5 mIU/L, based on clinical results and recent information on the relatively stable and narrow range of values in patients without thyroid disease. The terminology used for TSH results is clarified in an attempt to help physicians interpret, explain, and respond to TSH test results for their patients.


Thermogravimetric kinetic analysis and pollutant evolution during the pyrolysis and combustion of mobile phone case.
The increase in electronic waste, including cellular telephones, worldwide is a worrying reality. For this reason, urgent action on the management of these wastes is necessary within a framework that respects the environment and human health. Mobile phone components can be physically segregated through grinding at the dismantling sites, in order to reuse or reprocess (via chemical or physical recycling) the recovered plastics and valuable metals. A kinetic study of the thermal decomposition of a mobile phone case has been carried out under different conditions by thermogravimetry. Several experiments were performed in a nitrogen atmosphere (pyrolysis runs) and also in an oxidative atmosphere with two different oxygen concentrations (10% and 20% oxygen in nitrogen). Dynamic runs and dynamic+isothermal runs have been carried out to obtain much decomposition data under different operating conditions. Moreover some TG-MS runs were performed in order to better understand the thermal decomposition of a mobile phone case and identify some compounds emitted during the controlled heating of this material. A scheme of two independent reactions for pseudocomponents has been proposed for the pyrolysis process. For the combustion runs, the scheme proposed includes two pyrolytic reactions competing with other two reactions with formation of an intermediate residue, and finally the reaction of oxidation/burning of the intermediate residue. Furthermore, pyrolysis and combustion runs at 500 °C in a horizontal laboratory furnace were carried out. More than 50 compounds, including carbon oxides, light hydrocarbons, and polycyclic aromatic hydrocarbons (PAHs) have been identified and quantified. The main semivolatile compounds detected were phenol and styrene. Furthermore, polychlorodibenzo-p-dioxin and polychlorodibenzofurans (PCDD/Fs) and dioxin-like PCBs produced were analyzed. In the combustion run, PCDDs were obtained in higher amounts than PCDFs and HxCDD was the most emitted homologue.


Reducing ability of the striatum and cerebral cortex in rats following acute administration of risperidone or haloperidol: an estimation by in vivo electron paramagnetic resonance imaging.
In vivo temporal electron paramagnetic resonance (EPR) imaging of the blood-brain barrier-permeable nitroxide radical, 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidin-1-yloxy (PCAM), in the brain of rats was conducted following acute administration of risperidone (RSP) or haloperidol (HPD). The half-life of the signal intensity of PCAM was obtained from a selected area in the temporal EPR images. The half-lives in the striatum and cerebral cortex for the RSP- or HPD-treated rats were significantly longer than for the control rats (p < 0.01). This finding indicates that the reducing abilities of the striatum and cerebral cortex decreased in the rats to which either RSP or HPD had been acutely administrated because the half-life of PCAM in the selected region of the brain reflects its reducing ability.


Incidence of major adverse cardiovascular events with genotype test guided antiplatelet treatment strategy after percutaneous coronary intervention.
To estimate the incidence of major adverse cardiovascular events (MACE) with genotype test-guided antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome. Patients who had undergone PCI for acute coronary syndrome as well as stable coronary artery disease were recruited. Salivary samples were obtained from these patients and genotyped for CYP2C19∗2, CYP2C19∗3 variations by sequencing method (GAAP x method). Patients were categorized as normal (GG, GG) (29%), intermediate (AG) (52%) or poor metabolizes (homozygous variant AA) (19%). Dual antiplatelets were given based on the genotyping data. Poor metabolizes received newer agent (ticagrelor), intermediate metabolizes received double-dose of clopidogrel and normal metabolizes received therapeutic doses of clopidogrel. All subjects were followed-up for six months. Based on the genotyping data of CYP2C19∗2 and CYP2C19∗3 variations, it was found that most patients were categorized as 'intermediate' (78, 51.65%), followed by 'normal' (43, 28.48%) and 'poor' metabolizes (30, 19.87%). Only 3 (1.5%) of 151 patients reported MACE at follow-up. Genotyping for CYP2C19 variations to assess clopidogrel resistance in patients undergoing PCI and subsequent drug selection helps reduce MACE after coronary intervention.


Density-Fitting Method in Symmetry-Adapted Perturbation Theory Based on Kohn-Sham Description of Monomers.
We present a new implementation of symmetry-adapted perturbation theory of intermolecular interactions based on Kohn-Sham description of monomers. With density-fitting of molecular integrals, the scaling of the computational cost of the method is reduced from the sixth to the fifth power of the system size. Computational requirements of some operations scaling as the fifth power have also been significantly reduced. The new method allows an accurate treatment of molecules consisting of as many as a few dozen of atoms, using both nonhybrid and hybrid density functionals.


Clinical experience with pefloxacin in the therapy of typhoid fever.
Thirty hospitalized patients (22 men and eight women), aged between 15 and 41 years (mean = 25.4 years), with severe proven typhoid sepsis were treated with pefloxacin at daily dose of 1200 mg, divided in three doses, intravenously for the first five days and orally for the following ten days of treatment. All patients completely recovered from infection and pathogens were eradicated after 30 days of follow-up. In none of the patients was a relapse registered during the follow-up or enteric carrier state after disease. Pefloxacin therapy was well tolerated by all patients: in five patients a mild and transient epigastric pain and in one patient a mild and transient nausea were registered. Pefloxacin is a safe and effective agent for therapy of typhoid fever.


AMPK-dependent modulation of hepatic lipid metabolism by nesfatin-1.
The aim of this study was to characterize the mechanism by which peripheral nesfatin-1 regulates hepatic lipid metabolism. Continuous peripheral infusion of nesfatin-1 reduced adiposity and plasma levels of triglyceride and cholesterol. In mice fed high fat diet, peripheral nesfatin-1 significantly decreased hepatic steatosis measured by triglyceride content and oil red staining area and diameter. These alterations were associated with a significant reduction in lipogenesis-related transcriptional factors PPARγ and SREBP1, as well as rate-limited enzyme genes such as acaca, fasn, gpam, dgat1 and dgat2. In primary hepatocytes, nesfatin-1 inhibited both basal and oleic acid stimulated triglyceride accumulation, which was accompanied by a decrement in lipogenesis-related genes and an increase in β-oxidation-related genes. In cultured hepatocytes, nesfatin-1 increased levels of AMPK phosphorylation. Inhibition of AMPK by compound C blocked the reduction of triglyceride content elicited by nesfatin-1. Our studies demonstrate that nesfatin-1 attenuates lipid accumulation in hepatocytes by an AMPK-dependent mechanism.