Ultrasound guided rhomboid intercostal block: A pilot study to assess its analgesic efficacy in paediatric patients undergoing video-assisted thoracoscopy surgery.
Ultrasound guided rhomboid intercostal plane block (RIB) is a relatively new regional anaesthesia technique that has shown to provide dermatomal coverage from T2-9 on the whole anterior and posterior hemithorax. It has proved effective in providing preemptive analgesia in various surgeries like mastectomy and thoracotomy. The aim of the study was to study the efficacy of RIB in paediatric patients: 7 to 12 years undergoing thoracoscopic surgeries in terms of analgesic requirement, pain scores and adverse effects. In this randomised, prospective double-blind study, 40 American Society of Anesthesiologists I/II patients, of the age group 7-12 years scheduled for Video-assisted thoracoscopy (VATS) surgery were recruited. The patients were allocated to one of the two groups: group R: general anaesthesia + RIB (RIB group) and group F: general anaesthesia (FENT group). Perioperative opioid consumption and postoperative pain scores were recorded. Adverse effects like respiratory depression and nausea were also noted. Patients in group R required less intraoperative fentanyl dose (1.45 ± 0.65 vs 2.90 ± 0.45) (P < 0.05). Postoperative opioid consumption was also less in this group R (2.90 ± 0.91 vs 5.56 ± 1.08) (P < 0.05). Less number of patients experienced nausea (2 vs 6) and respiratory depression (2 vs 7) in group R. Ultrasound guided RIB reduces perioperative opioid consumption in patients undergoing VATS surgery with lesser postoperative pain scores.


Radionuclide skeletal scanning in dentistry.
Radionuclide bone scanning have revolutionized skeletal imaging and is a superior aid in detecting pathophysiologic changes of bone as compared to plain radiography. Radionuclide skeletal scanning has proved to be a valuable and beneficial tool in early and differential diagnosis of maxillofacial lesions. Moreover, skeletal scanning is helpful in treatment planning and follow-up after therapy of various orofacial infections.


Regio- and conformational isomerization critical to design of efficient thermally-activated delayed fluorescence emitters.
Regio- and conformational isomerization are fundamental in chemistry, with profound effects upon physical properties, however their role in excited state properties is less developed. Here two regioisomers of bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide, a donor-acceptor-donor (D-A-D) thermally-activated delayed fluorescence (TADF) emitter, are studied. 2,8-bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide exhibits only one quasi-equatorial conformer on both donor sites, with charge-transfer (CT) emission close to the local triplet state leading to efficient TADF via spin-vibronic coupling. However, 3,7-bis(10H-phenothiazin-10-yl)dibenzo[b,d]thiophene-S,S-dioxide displays both a quasi-equatorial CT state and a higher-energy quasi-axial CT state. No TADF is observed in the quasi-axial CT emission. These two CT states link directly to the two folded conformers of phenothiazine. The presence of the low-lying local triplet state of the axial conformer also means that this quasi-axial CT is an effective loss pathway both photophysically and in devices. Importantly, donors or acceptors with more than one conformer have negative repercussions for TADF in organic light-emitting diodes.


Effects of pump versus twice-daily injection delivery of synthetic parathyroid hormone 1-34 in children with severe congenital hypoparathyroidism.
To compare the response with synthetic human parathyroid hormone (PTH) 1-34 delivered by twice-daily injection vs insulin pump in children with severe congenital hypoparathyroidism due to calcium receptor mutation or autoimmune polyglandular syndrome type 1. Children and young adults aged 7-20 years with congenital hypoparathyroidism (N = 12) were randomized to receive PTH 1-34, delivered either by twice-daily subcutaneous injection or insulin pump for 13 weeks, followed by crossover to the opposite delivery method. The principal outcome measures were serum and urine calcium levels. Secondary outcomes included serum and urine magnesium and phosphate levels and bone turnover markers. PTH 1-34 delivered via pump produced near normalization of mean serum calcium (2.02 ± 0.05 [pump] vs 1.88 ± 0.03 [injection] mmol/L, P < .05, normal 2.05-2.5 mmol/L), normalized mean urine calcium excretion (5.17 ± 1.10 [pump] vs 6.67 ± 0.76 mmol/24 h/1.73 m(2), P = .3), and significantly reduced markers of bone turnover (P < .02). Serum and urine calcium and magnesium showed a biphasic pattern during twice-daily injection vs minimal fluctuation during pump delivery. The PTH 1-34 dosage was markedly reduced during pump delivery (0.32 ± 0.04 vs 0.85 ± 0.11 μg/kg/d, P < .001), and magnesium supplements were also reduced (P < .001). Compared with twice-daily delivery, pump delivery of PTH 1-34 provides more physiologic calcium homeostasis and bone turnover in children with severe congenital hypoparathyroidism.


[Effect of leponex on the ultrastructure of the brain].
Electron microscopic examination of the black substance, olfactory tubercle and head of the rat caudate nucleus was made upon a single and a 3-week administration of the antipsychotic drug leponex in a dose of 10 mg/kg. It was shown that leponex induces hyperproduction of the mitochondria, changes in sizes and form of neuronal bodies and processes, and the formation of the membranous structures in presynaptic endings. These changes were attended by ultrastructural shifts in neurons and glia. The data are considered as compensatory processes of mediator receptors of the brain.


Pepsinogen synthesis and secretion in isolated gastric glands.
De novo synthesis of pepsinogen was shown in isolated rabbit and human gastric glands after incubation of the glands in a 14C labelled amino acid enriched minimum Eagles medium. At regular intervals, glands and medium were separated and analysed by polyacrylamide gel electrophoresis. Newly synthesised pepsinogen was shown by autoradiography. Incorporation of 14C labelled amino acids was detected after only 30 min of culture and increased almost linearly in time for 4 h. By comparing the incorporation of label into total protein and into pepsinogen, it was concluded that pepsinogen formed 70-90% of the newly synthesised protein. Cimetidine, at a concentration of 160 micrograms/ml, strongly inhibited the synthesis of pepsinogen. Spontaneous secretion of pepsinogen into the medium was very low and relatively constant. Dibutyryl cyclic AMP considerably stimulated the secretion of pepsinogen into the medium. Histamine and pentagastrin did not influence the release of pepsinogen. These results show that isolated gastric glands are capable of synthesis and secretion of pepsinogen and that both can be selectively stimulated and inhibited.


Immunocytochemical studies of blood group A, H, I, and i antigens in gastric mucosae of infants with normal gastric histology and of patients with gastric carcinoma and chronic benign peptic ulceration.
Indirect immunofluorescence studies of blood group A, H, I, and i antigens were performed on the gastric mucosae and tumor tissues of patients with gastric carcinoma, on the mucosae of patients with chronic benign gastric ulceration, and on the mucosae of infants who had died of causes other than gastrointestinal disease. The following findings were of particular interest: (1) Normal 'secretor' type mucosae were distinguishable from 'non-secretor' type mucosae by the uniform staining of the A or H antigens at the surface and in the pits. Normal 'non-secretor' type mucosae showed little staining of the H or A antigens but, instead, there was staining with anti-I(Ma) antibody. Staining with anti-I(Step) and anti-i(Den) did not show a clear correlation with the 'secretor'/'non-secretor' status of the normal mucosae. (2) Apparently normal areas of gastric mucosae of patients with gastric carcinoma or the normal part of gastric mucosae of patients with benign gastric ulcer frequently showed focal areas of loss or gain of the blood group antigens as is often seen in gastric carcinoma tissues. (3) In the mucosae of patients with intestinal metaplasia there was marked loss of A/H antigens in 'secretors' and I(Ma) antigen in 'non-secretors'. (4) Staining characteristics of tissues from gastric carcinoma were:(a) Focal loss of the expected A/H or I antigens was observed with much variation in staining from area to area, but only a minority showed complete loss of the expected staining. (b) A majority of the carcinomas from 'secretors' showed foci of substantial staining with anti-I(Ma) in contrast to normal 'secretor' mucosae. This is probably due to incomplete biosynthesis of A/H determinants. (c) Incompatible A-like staining by a rabbit anti-A serum was observed in one out of nine adenocarcinomas from blood group B or O persons. (d) A few cases showed substantial i antigen staining. The aberrant expression of blood group A, H, I, and i antigens in neoplastic as well as in some areas of morphologically normal mucosa of patients with benign and malignant diseases of the stomach is discussed in the context of current biochemical knowledge.


Group B Streptococcus Cas9 variants provide insight into programmable gene repression and CRISPR-Cas transcriptional effects.
Group B Streptococcus (GBS; S. agalactiae ) causes chorioamnionitis, neonatal sepsis, and can also cause disease in healthy or immunocompromised adults. GBS possesses a type II-A CRISPR-Cas9 system, which defends against foreign DNA within the bacterial cell. Several recent publications have shown that GBS Cas9 influences genome-wide transcription through a mechanism uncoupled from its function as a specific, RNA-programmable endonuclease. We examine GBS Cas9 effects on genome-wide transcription through generation of several isogenic variants with specific functional defects. We compare whole-genome RNA-seq from Δ cas9 GBS with a full-length Cas9 gene deletion; dcas9 defective in its ability to cleave DNA but still able to bind to frequently occurring protospacer adjacent motifs; and scas9 that retains its catalytic domains but is unable to bind protospacer adjacent motifs. Comparing scas9 GBS to the other variants, we identify nonspecific protospacer adjacent motif binding as a driver of genome-wide, Cas9 transcriptional effects in GBS. We also show that Cas9 transcriptional effects from nonspecific scanning tend to influence genes involved in bacterial defense and nucleotide or carbohydrate transport and metabolism. While genome-wide transcription effects are detectable by analysis of next-generation sequencing, they do not result in virulence changes in a mouse model of sepsis. We also demonstrate that catalytically inactive dCas9 expressed from the GBS chromosome can be used with a straightforward, plasmid-based, single guide RNA expression system to suppress transcription of specific GBS genes without potentially confounding off-target effects. We anticipate that this system will be useful for study of nonessential and essential gene roles in GBS physiology and pathogenesis.


Chemotherapy for advanced gastric cancer: slow but further progress.
Gastric cancer remains a significant problem in terms of global health, and is the most common cancer in Korea. Surgery is the only potentially curative treatment for localized gastric cancer, but most cases present at an advanced stage. Randomized trials have demonstrated that chemotherapy for advanced gastric cancer improves the quality of life and extends survival, by 4 approximately 6 months, compared with best supportive care alone. Single agents with a proven activity in a first-line setting include 5-fluorouracil (5-FU), doxorubicin, mitomycin C, cisplatin, taxanes (docetaxel and paclitaxel) and oral fluoropyrimidines (capecitabine and TS-1). Based on the results from several large scale randomized trials, FP (5-FU/cisplatin) and ECF (epirubicin/cisplatin/5-FU) combinations are the most widely used regimen against advanced gastric cancer. Phase II studies of the FP and ECF combination reported a 40~51% response rate in previously untreated patients, and this regimen also produced a significantly higher response rate than the FAM (5-FU/doxorubicin/mitomycin) and FAMTX (5-FU/doxorubicin/methotrexate) regimens, respectively. However, significant treatment related-toxicities and discomfort were reported from ECF, which prevents this combination from becoming the standard treatment regimen. While no one combination chemotherapy regimen is accepted as the standard for advanced gastric cancer, FP is currently considered a suitable reference regimen worldwide. New agents, such as taxane, irinotecan and oxaliplatin, combined with old agents, such as cisplatin and 5-FU, are currently under evaluation to further improve treatment outcomes. Also, oral 5-FU prodrugs are replacing the cumbersome 5-FU long-term infusion due to its convenience and superior toxicity profile. However, the low complete response rate and short response duration are still the main obstacles in the chemotherapy for gastric cancer. Only large scale comparative clinical trials will give clues to improve the results of gastric cancer treatments.


Frequency of Heterozygous Parkin (PRKN) Variants and Penetrance of Parkinson's Disease Risk Markers in the Population-Based CHRIS Cohort.
Mutations in the Parkin (PRKN) gene are the most frequent cause of autosomal recessive early-onset Parkinson's disease (PD). Heterozygous PRKN mutation carriers might also be at increased risk for developing clinical symptoms of PD. Given the high frequency of heterozygous mutations in the general population, it is essential to have better estimates of the penetrance of these variants, and to investigate, which clinical and biochemical markers are present in carriers and thus potentially useful for identifying those individuals at greater risk of developing clinical symptoms later in life. In the present study, we ascertained the frequency of heterozygous PRKN mutation carriers in a large population sample of the Cooperative Health Research in South Tyrol (CHRIS) study, and screened for reported PD risk markers. 164 confirmed heterozygous PRKN mutation carriers were compared with 2,582 controls. A higher number of heterozygous mutation carriers reported a detectable increase in an akinesia-related phenotype, and a higher percentage of carriers had manifested diabetes. We also observed lower resting heart rate in the PRKN mutation carriers. Extending our risk analyses to a larger number of potential carriers and non-carriers using genotype imputation (n = 299 carriers and n = 7,127 non-carriers), from previously published biomarkers we also observed a higher neutrophil-to-lymphocyte ratio (NLR) and lower serum albumin and sodium levels in the heterozygous PRKN variant carriers. These results identify a set of biomarkers that might be useful either individually or as an ensemble to identify variant carriers at greater risk of health issues due to carrier status.


The world of poultry disease.
The production of poultry meat and eggs is presented for the top 40 countries producing these products. Seventy per cent of poultry meat and eggs are produced by 10 countries. Production per capita is between five and six times lower in developing than in developed countries. Poultry meat and eggs form as great a proportion of the animal protein diet of members of developing as of developed countries. The nutritional efficiency of both poultry meat and egg production with respect to energy is similar to the production of milk and only second to pig meat; in respect of protein production both poultry meat and eggs are only second to milk. It is concluded that the developments that have occurred in the husbandry and management of poultry in the developed countries are likely to occur in developing countries. Data for the incidence of disease in developing and developed countries is presented and discussed. Although the relative importance of diseases may differ between countries and geographical areas there are few important diseases which are unique to particular parts of the world. Figures for the U.S.A. indicate that total economic loss from disease is about 20% of the value of poultry production and is about three times the loss from mortality. The principal methods of disease control are discussed and include: preventive treatment, vaccination, eradication and breeding for resistance. It is considered that infectious disease will continue to be the major cause of economic loss from disease. It is suggested that future developments in disease control will use the techniques of genetic engineering from the production of vaccines and developing stocks resistant to disease.


Azo dying of α-keratin material improves microbial keratinase screening and standardization.
Microbial conversion through enzymatic reactions has received a lot of attention as a cost-effective and environmentally friendly way to recover amino acids and short peptides from keratin materials. However, accurate assessment of microbial keratinase activity is not straightforward, and current available methods lack sensitivity and standardization. Here, we suggest an optimized Azokeratin assay, with substrate generated directly from azo-dyed raw keratin material. We introduced supernatant filtration in the protocol for optimal stopping of keratinase reactions instead of the widely used trichloroacetic acid (TCA), as it generated biases and impacted the sensitivity. We furthermore suggest a method for standardization of keratinase activity signals using proteinase K, a well-known keratinase, as a reference enabling reproducibility between studies. Lastly, we evaluated our developed method with several bacterial isolates through benchmarking against a commercial assay (Keratin Azure). Under different setups, the Azokeratin method was more sensitive than commonly used Keratin Azure-based assays (3-fold). We argue that this method could be applied with any type of keratin substrate, enabling more robust and sensitive results which can be used for further comparison with other studies, thus representing an important progress within the field of microbial keratin degradation.


Hernioplasty using the hernial sac in repair of inguinal hernia.
Hernioplasty with use of the hernial sac appears to offer advantages over operations previously used to repair large defects in the posterior wall of the inguinal canal. This operation was performed on 66 patients without recurrence of the lesion in the 55 patients for whom follow-up data are available.


A variational Bayesian mixture modelling framework for cluster analysis of gene-expression data.
Accurate subcategorization of tumour types through gene-expression profiling requires analytical techniques that estimate the number of categories or clusters rigorously and reliably. Parametric mixture modelling provides a natural setting to address this problem. We compare a criterion for model selection that is derived from a variational Bayesian framework with a popular alternative based on the Bayesian information criterion. Using simulated data, we show that the variational Bayesian method is more accurate in finding the true number of clusters in situations that are relevant to current and future microarray studies. We also compare the two criteria using freely available tumour microarray datasets and show that the variational Bayesian method is more sensitive to capturing biologically relevant structure.


A retrospective analysis of the role of adjuvant radiotherapy in the treatment of cutaneous melanoma.
Melanoma is a significant clinical problem, with rising rates of incidence. Surgery is the mainstay of treatment. The role of adjuvant radiotherapy in the control of locoregionally advanced cutaneous melanoma is controversial. A retrospective study of the Surveillance, Epidemiology, and End Results (SEER) database was performed. Patients with locoregionally confined cutaneous melanoma treated surgically between 2004 and 2009 were evaluated, with cancer-specific and all-cause mortality as primary end points. Propensity score matching was used to match 319 radiotherapy patients with 319 non-radiotherapy controls, stratifying by head and neck (HN) and non-head and neck (NHN) primary. Surgery was primarily by wide excision in both the radiotherapy (51.72%) and non-radiotherapy (53.91%) groups. The majority had nodal disease (82.13% vs. 82.44%). White (91.22% vs. 90.59%) males (70.21% vs. 68.96%) predominated. Average ages at diagnosis were 62.27 (SD 15.93) and 63.02 (SD 16.03). Using Cox proportional hazards models, radiation conferred decreased survival in all-cause (HR 1.44, p < 0.0003), and cancer specific mortality (HR 1.57, p < 0.0002) in combined analysis. The NHN group showed significantly decreased 6-year cancer specific survival (HR 2.05, p < 0.0001) for radiated patients. The HN group showed a non-significant hazard with radiotherapy (HR 1.19, p = 0.307). Meaningful differences not captured in the SEER database may exist between cohorts. Based on available SEER data, routine use of adjuvant radiotherapy should be viewed with caution and reserved for high-risk patients. Future trials evaluating patient quality of life may clarify the benefit of adjuvant radiotherapy in high-risk melanoma populations.


Mesoporous Zirconia Coating for Sensing Applications Using Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy.
Mid-infrared attenuated total reflection (ATR) spectroscopy is a powerful tool for in situ monitoring of various processes. Mesoporous silica, an extensively studied material, has already been applied in sensing schemes due to its high surface area and tunable surface chemistry. However, its poor chemical stability in aqueous solutions at pH values higher than 8 and strong absorption below 1250 cm-1 limits its range of applications. To circumvent these problems, a mesoporous zirconia coating on ATR crystals was developed. Herein, the synthesis, surface modification, and characterization of ordered mesoporous zirconia films on Si wafers and Si-ATR crystals are presented. The modified coating was applied in sensing schemes using aromatic and aliphatic nitriles in aqueous solution as organic pollutants. The mesoporous zirconia coating shows strong chemical resistance when kept in alkaline solution for 72 h. The success of surface modification is confirmed using Fourier transform infrared (FT-IR) spectroscopy and contact angle measurements. Benzonitrile and valeronitrile in water are used as model analytes to evaluate the enrichment performance of the film. The experimental results are fitted using Freundlich isotherms, and enrichment factors of 162 and 26 are calculated for 10 mg L-1 benzonitrile and 25 mg L-1 valeronitrile in water, respectively. Limits of detection of 1 mg L-1 for benzonitrile and 11 mg L-1 for valeronitrile are obtained. The high chemical stability of this coating allows application in diverse fields such as catalysis with the possibility of in situ monitoring using FT-IR spectroscopy.


Formulation and Characterization of a New Injectable Bone Substitute Composed PVA/Borax/CaCO3 and Demineralized Bone Matrix.
The occurrence of bone-related disorders and diseases has dramatically increased in recent years around the world. Demineralized bone matrix (DBM) has been widely used as a bone implant due to its osteoinduction and bioactivity. However, the use of DBM is limited because it is a particulate material, which makes it difficult to manipulate and implant with precision. In addition, these particles are susceptible to migration to other sites. To address this situation, DBM is commonly incorporated into a variety of carriers. An injectable scaffold has advantages over bone grafts or preformed scaffolds, such as the ability to flow and fill a bone defect. The aim of this research was to develop a DBM carrier with such viscoelastic properties in order to obtain an injectable bone substitute (IBS). The developed DBM carrier consisted of a PVA/glycerol network cross-linked with borax and reinforced with CaCO3 as a pH neutralizer, porosity generator, and source of Ca. The physicochemical properties were determined by an injectability test, FTIR, SEM, and TGA. Porosity, degradation, bioactivity, possible cytotoxic effect, and proliferation in osteoblasts were also determined. The results showed that the developed material has great potential to be used in bone tissue regeneration.


Use of the seven principles of effective teaching to design and deliver an interactive hybrid nursing research course.
This study examined how applying the seven principles of effective teaching to designing and delivering an undergraduate nursing research course in a hybrid format affected course quality. Existing research does not adequately describe how the design and delivery processes of hybrid courses affect course outcomes or how these processes address informatics learning resources and students' varying levels of computer skills. A hybrid nursing research course was designed and delivered to 105 nursing students using Blackboard and Tegrity systems. Using a mixed-methods approach, students' satisfaction with the course was measured and achievement was compared with those of a comparable previous cohort that had taken the same course in the traditional format. Students reported high satisfaction with the course and obtained significantly higher scores than students in the previous semester. Concerns included working in groups and the additional workload associated with the online component. CONCLUSION Applying the seven principles of effective teaching in design and delivery can improve the quality of hybrid courses.


Mental health of South Asian youth in Peel Region, Toronto, Canada: a qualitative study of determinants, coping strategies and service access.
This qualitative study set out to understand the mental health challenges and service access barriers experienced by South Asian youth populations in the Peel Region of Toronto, Canada. In-depth semistructured interviews were carried out with South Asian youth living in Peel Region (Mississauga, Brampton and Caledon), a suburb of Toronto, Canada, home to over 50% of Ontario's South Asian population. South Asian youth (n=10) engaged in thoughtful, candid dialogue about their mental health and service access barriers. Qualitative interview themes related to mental health stressors and mental health service access barriers experienced by youth living in Peel Region were assessed using thematic analysis. South Asian youth face many mental health stressors, from intergenerational and cultural conflict, academic pressure, relationship stress, financial stress and family difficulties. These stressors can contribute to mental health challenges, such as depression and anxiety and drug use, with marijuana, alcohol and cigarettes cited as the most popular substances. South Asian youth were only able to identify about a third (36%) of the mental health resources presented to them and did not feel well informed about mental health resources available in their neighbourhood. They offered recommendations for improved youth support directed at parents, education system, South Asian community and mental health system. Institutions and bodies at all levels of the society have a role to play in ensuring the mental health of South Asian youth.


Tangrams: a simple visual tool for communicating the complexities of professionalism.
Professionalism is vital for high quality healthcare and fundamental to health profession education. It is however complex, hard to define and can be challenging to teach, learn about and assess. We describe the development and use of an innovative visual tool, using a tangram analogy, to introduce and explore core professionalism concepts, which are often troublesome for both learners and educators. These include the hidden curriculum, capability, professional identity and the difference between unprofessionalism and high professional standards. Understanding these concepts can help individuals to see professionalism differently, encourage faculty to design professionalism programmes which focus on professional excellence, support assessors to feel more confident in identifying and addressing underperformance and facilitate learners to appreciate the complexity and uncertainty inherent in professionalism and to become more alert to the hidden curriculum and its potential impact. We have used the tangram model to educate for professionalism in multiple contexts with learners and educators. Participants regularly report that it leads to a deeper understanding and important new insights around professionalism and helps them identify ways of changing their practice. We believe this approach has relevance across the health professions and suggest ways it could be further developed to explore wider professionalism issues such as reflective practice, resilience and teamworking.


Resilience to mental disorders in a low-income, non-Westernized setting.
Cross-national studies have found, unexpectedly, that mental disorder prevalence is higher in high-income relative to low-income countries, but few rigorous studies have been conducted in very low-income countries. This study assessed mental disorders in Nepal, employing unique methodological features designed to maximize disorder detection and reporting. In 2016-2018, 10714 respondents aged 15-59 were interviewed as part of an ongoing panel study, with a response rate of 93%. The World Mental Health version of the Composite International Diagnostic Interview (WMH-CIDI 3.0) measured lifetime and 12-month prevalence of selected anxiety, mood, alcohol use, and impulse control disorders. Lifetime recall was enhanced using a life history calendar. Lifetime prevalence ranged from 0.3% (95% CI 0.2-0.4) for bipolar disorder to 15.1% (95% CI 14.4-15.7) for major depressive disorder. The 12-month prevalences were low, ranging from 0.2% for panic disorder (95% CI 0.1-0.3) and bipolar disorder (95% CI 0.1-0.2) to 2.7% for depression (95% CI 2.4-3.0). Lifetime disorders were higher among those with less education and in the low-caste ethnic group. Gender differences were pronounced. Although cultural effects on reporting cannot be ruled out, these low 12-month prevalences are consistent with reduced prevalence of mental disorders in other low-income countries. Identification of sociocultural factors that mediate the lower prevalence of mental disorders in low-income, non-Westernized settings may have implications for understanding disorder etiology and for clinical or policy interventions aimed at facilitating resilience.


IL-17A Orchestrates Reactive Oxygen Species/HIF1α-Mediated Metabolic Reprogramming in Psoriasis.
Immune cell-derived IL-17A is one of the key pathogenic cytokines in psoriasis, an immunometabolic disorder. Although IL-17A is an established regulator of cutaneous immune cell biology, its functional and metabolic effects on nonimmune cells of the skin, particularly keratinocytes, have not been comprehensively explored. Using multiomics profiling and systems biology-based approaches, we systematically uncover significant roles for IL-17A in the metabolic reprogramming of human primary keratinocytes (HPKs). High-throughput liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy revealed IL-17A-dependent regulation of multiple HPK proteins and metabolites of carbohydrate and lipid metabolism. Systems-level MitoCore modeling using flux-balance analysis identified IL-17A-mediated increases in HPK glycolysis, glutaminolysis, and lipid uptake, which were validated using biochemical cell-based assays and stable isotope-resolved metabolomics. IL-17A treatment triggered downstream mitochondrial reactive oxygen species and HIF1α expression and resultant HPK proliferation, consistent with the observed elevation of these downstream effectors in the epidermis of patients with psoriasis. Pharmacological inhibition of HIF1α or reactive oxygen species reversed IL-17A-mediated glycolysis, glutaminolysis, lipid uptake, and HPK hyperproliferation. These results identify keratinocytes as important target cells of IL-17A and reveal its involvement in multiple downstream metabolic reprogramming pathways in human skin.


The isolated perfused bovine liver.
1. A procedure is described for surgically isolating and artificially perfusing the liver of the young bovine. Heparinized autogenous blood from the hepatectomized animal diluted with Krebs-Ringer-bicarbonate solution is employed as the perfusate. 2. This preparation has been satisfactorily reproducible in this laboratory in more than 90 separate sequential perfusions. Absence of a sensitive hepatic venous smooth musculature contributes to the ability to maintain satisfactory perfusion for as long as 24 hours. 3. The perfusate was usually maintained bacterially free for at least the first 12 hours of perfusion without the use of antibiotics. The perfusate was maintained at normal body temperature and, by varying the CO(2) content of the oxygenating gas, within a physiological pH range. The importance of these features when studying problems of intermediary biochemistry and ultrastructure is emphasized. 4. The liver of the bovine calf is sufficiently large to permit (a) simultaneous and independent perfusion through the hepatic artery and portal vein, and (b) repeated sampling of hepatic tissue without interruption of the circulation. 5. Excellent, viable condition of the isolated liver, throughout many hours of perfusion, was demonstrated by steady state of oxygen consumption, efficient clearance of bromsulphalein dye, continuous secretion of bile, constancy of blood flows and pressures, and very minimal alterations from normal in histologic and ultrastructural detail.


DMF-MALDI: droplet based microfluidic combined to MALDI-TOF for focused peptide detection.
We present an automated droplet microfluidic system (DMF) to generate monitored nanoliter aqueous droplets in oil and their deposition on a commercial stainless steel plate for MALDI-TOF analysis of peptides or protein digests. We demonstrate that DMF-MALDI combination focuses the analyte on the MALDI plate, increasing considerably the homogeneity of the dried material. This results in a 30times enhanced MALDI-TOF MS signal for a model peptide, allowing a significant improvement of the detection sensitivity limit (down to few tens of attomoles). Moreover, positive detection can be achieved from sub-nanomolar peptides solutions and better overall protein sequence coverages are obtained from few tens attomoles of protein digest. These results make DMF-MALDI a promising approach for the treatment of peptides samples as well as a key component for an integrated approach in the proteomic field.


Origin of directionality in the fish stripe pattern.
The formation of stripe patterns in animal skin has been explained by the reaction-diffusion (RD) system, a hypothetical chemical reaction proposed by A. Turing. Although animal stripes usually have directionality, the RD model alone cannot explain how the direction is specified. To investigate the mechanism regulating the direction of stripes, we studied stripe pattern formation in two species of Genicanthus during sexual conversion. These species share almost identical morphologic properties, except for their stripe direction. In both species, spots transiently arise at random positions and then combine and rearrange to form directional stripes. Computational analysis has shown that diffusion anisotropy is very effective at specifying the direction of stripes formed by the RD system. Model simulations reproduce the transient dynamics of directional pattern formation observed in fish as well as the resulting stripes. In cases where the magnitude and direction of diffusion anisotropy of the substances are identical, the resulting stripes are not directional. However, if they differ, stripes become directional. As only a small difference in anisotropy is required for this effect, any kind of structure with directional conformation might cause a marked change in stripe direction. Scales are the most likely candidate structure for generating anisotropic interactions in skin.


Long term sexual outcomes of Mayer Rokitansky Küster Hauser Syndrome patients after Uncu-modified Davydov procedure.
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome has an incidence of 1 in 4000. The absence of the vagina and uterus results in sexual dysfunction and infertility. The first-line treatment is vaginal dilatation. There exists a number of second-line surgical options including the Uncu-modified Davydov procedure. To determine the complication rate, anatomical outcomes, and long-term sexual outcomes of MRKH syndrome patients after Uncu-modified Davydov procedure. Patients with MRKH syndrome who underwent paramesonephric remnant-supported laparoscopic double-layer peritoneal pull-down vaginoplasty (aka Uncu-modified Davydov procedure) between January 2008 and December 2021. The procedure involves laparoscopic circular dissection of the pelvic peritoneum followed by pulling down, through the opened vaginal orifice, and suturing the vaginal cuff with the support of uterine remnants. The long-term complication rate, anatomical outcomes, and sexual function outcomes (as measured by Female Sexual Function Index (FSFI)) were ascertained. Main Outcome Measures: The long-term complication rate, anatomical outcomes and FSFI survey results. A total of 50 patients with MRKH syndrome underwent the Uncu-modified Davydov procedure between Jan 2008- Dec 2021. There were four perioperative complications: three bladder injuries (6%) and one rectal serosa injury (2%). Four long-term postoperative complications were identified: one vesicovaginal fistula (2%), one recto-vaginal fistula (2%), and two vaginal stenoses (4%). All patients were physically examined at least one year after surgery. The mean vaginal length was 8.4 + 1.9 cm. The mean FSFI score was 31.5 + 3.9 (minimum score of 24, maximum score of 36). Conclusion: The Uncu-modified Davydov procedure has been demonstrated to be a safe and effective treatment option with high female sexual function index scores for patients with MRKH syndrome. The long-term complication rate, anatomical and sexual outcomes of Uncu-modified laparoscopic peritoneal pull-down vaginoplasty were reported in this study. The results indicated that the surgical approach could be used in selective MRKH patients who failed first-line self-dilatation therapy.


Control of advanced and refractory acute myelogenous leukaemia with sirolimus-based non-myeloablative allogeneic stem cell transplantation.
Non-myeloablative conditioning has extended the use of allogeneic haematopoietic transplant to many previously ineligible patients. We added the immunosuppressive and antitumour agent sirolimus (rapamycin) to an established transplant regimen of fludarabine 25 mg/m(2) days -7 through -3 and cyclophosphamide 1000 mg/m(2) days -7 and -6, with tacrolimus and methotrexate immunoprophyllaxis. A total of 23 patients with acute myelogenous leukaemia (AML) were treated, with a median age of 59 years (range: 28-72) at transplant. Only seven patients in total were in complete remission prior to transplantation. Nine patients were in chemotherapy-refractory progression and seven were primarily refractory to induction therapy. Six patients received matched sibling, 11 unrelated donor, 1-5/6 matched and five haploidentical (haplo - three of six or four of six matched) transplants. The haplo-recipients also received antithymocyte globulin, all patients engrafted. Only two, both recipients of haploidentical cells, have died from transplant-related causes. Twelve of 23 patients survived at 198-1162-d post-transplant (median 578). Four of 12 survivors relapsed at 83, 88, 243 and 508 d and three were in remission after chemotherapy and donor lymphocyte infusion. Although follow up is short, this data suggests that non-myeloablative haematopoietic cell transplantation with sirolimus (rapamycin)-based immunosuppression may provide disease control over several years in some patients with advanced and poor prognosis AML.


Non-Thermal Plasma Treatment of Poly(tetrafluoroethylene) Dental Membranes and Its Effects on Cellular Adhesion.
Non-resorbable dental barrier membranes entail the risk of dehiscence due to their smooth and functionally inert surfaces. Non-thermal plasma (NTP) treatment has been shown to increase the hydrophilicity of a biomaterials and could thereby enhance cellular adhesion. This study aimed to elucidate the role of allyl alcohol NTP treatment of poly(tetrafluoroethylene) in its cellular adhesion. The materials (non-treated PTFE membranes (NTMem) and NTP-treated PTFE membranes (PTMem)) were subjected to characterization using scanning electron microscopy (SEM), contact angle measurements, X-ray photoelectron spectroscopy (XPS), and electron spectroscopy for chemical analysis (ESCA). Cells were seeded upon the different membranes, and cellular adhesion was analyzed qualitatively and quantitatively using fluorescence labeling and a hemocytometer, respectively. PTMem exhibited higher surface energies and the incorporation of reactive functional groups. NTP altered the surface topography and chemistry of PTFE membranes, as seen through SEM, XPS and ESCA, with partial defluorination and polymer chain breakage. Fluorescence labeling indicated significantly higher cell populations on PTMem relative to its untreated counterparts (NTMem). The results of this study support the potential applicability of allyl alcohol NTP treatment for polymeric biomaterials such as PTFE-to increase cellular adhesion for use as dental barrier membranes.


Objective Sensory Testing Methods Reveal a Higher Prevalence of Olfactory Loss in COVID-19-Positive Patients Compared to Subjective Methods: A Systematic Review and Meta-Analysis.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify the causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords "COVID-19," "smell," and/or "olfaction." We included any study that quantified smell loss (anosmia and hyposmia) as a symptom of COVID-19. Studies were grouped and compared based on the type of method used to measure smell loss-subjective measures, such as self-reported smell loss, versus objective measures using rated stimuli-to determine if prevalence differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbances. We identified 34 articles quantifying anosmia as a symptom of COVID-19 (6 objective and 28 subjective), collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4-89.2%) and 44% with subjective measurements (95% CI of 32.2-57.0%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2; the use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss.


[Mushroom worker's lung caused by inhalation of spores of the edible fungus pleurotus Florida ("oyster mushroom") (author's transl)].
A new edible mushroom, known as oyster mushroom (Pleutrotus Florida, variety of Pleurotus ostreatus) has recently gained commercial importance in Europe, having been imported from the U.S.A. in 1963 and cultivated in Germany between 1972 and 1973. Several persons concerned with the cultivation and industrial production of this mushroom fell ill, after close contact with it over a period of some months, with exhaustion, headache, chills and fever, and cough. These symptoms, similar to those of "farmer's lung" were proved to be caused by the spores of Pleurotus Florida, inhaled in harvesting rooms. The suspicion of an allergic disease, is supported by the history and clinical picture, and the demonstration of precipitating antibodies against spore extracts (Ouchterlony test). The antigens probably have a high molecular weight and are fixed to the spore membrane. Experimental sensitisation of rabbits also revealed precipitins. One of three isolated antigens produced antibodies identical in man and rabbit.


Pediatric rehabilitation: trends in length of stay.
Length of stay (LOS) is one of the most important pieces of data used to measure clinical rehabilitation outcomes, but there is a paucity of LOS data regarding pediatric acute rehabilitation. The purpose of this study was to predict LOS based on admission diagnosis to an acute pediatric inpatient rehabilitation unit. The hypothesis was that LOS will vary according to admission diagnosis. One thousand one hundred forty-five patients were admitted to our acute inpatient rehabilitation unit from January 1, 2000 to December 31, 2007. Common admission impairment groups were orthopedic conditions (29.3%), brain injury (17.9%), brain tumor (7.9%), pain syndrome (7.5%), complex medical conditions (7.4%), stroke (7.2%), meningoencephalitis (7.2%), and spinal cord injury (4.4%). The distribution of LOS data was significantly skewed to the right (for example, mean 40.6 days and median 26 days, respectively, in brain injury group). The median LOS of patients admitted with orthopedic conditions was the shortest (13 days), compared to patients admitted with spinal cord lesions, which was the longest (32 days). Logarithm-transformed mean LOS was different among the admission impairment groups (F=28.7, p < 0.01). However Tukey's Honestly Significance Difference test further showed that: 1) LOS data was not always statistically different across admission impairment groups, and 2) LOS of patients with orthopedic conditions and spinal cord lesions was the shortest and longest, respectively, compared to other admission impairment groups. No proportional decrease in median LOS was observed across the impairment groups from 2000 to 2007. LOS for pediatric acute inpatient rehabilitation varied according to admission diagnosis. When considering future comprehensive pediatric rehabilitation outcome studies, focusing on a uniform impairment group is suggested. In addition, attention to other factors such as functional status changes, severity of illness, payment types, and psychosocioeconomic status should be considered.


Characterization of the binding of metoprolol tartrate and guaifenesin drugs to human serum albumin and human hemoglobin proteins by fluorescence and circular dichroism spectroscopy.
The interactions of metoprolol tartrate (MPT) and guaifenesin (GF) drugs with human serum albumin (HSA) and human hemoglobin (HMG) proteins at pH 7.4 were studied by fluorescence and circular dichroism (CD) spectroscopy. Drugs quenched the fluorescence spectra of HSA and HMG proteins through a static quenching mechanism. For each protein-drug system, the values of Stern-Volmer quenching constant, bimolecular quenching constant, binding constant and number of binding site on the protein molecules were determined at 288.15, 298.15, 310.15 and 318.15 K. It was found that the binding constants of HSA-MPT and HSA-GF systems were smaller than those of HMG-MPT and HMG-GF systems. For both drugs, the affinity of HMG was much higher than that of HSA. An increase in temperature caused a negative effect on the binding reactions. The number of binding site on blood proteins for MPT and GF drugs was approximately one. Thermodynamic parameters showed that MPT interacted with HSA through electrostatic attraction forces. However, hydrogen bonds and van der Waals forces were the main interaction forces in the formation of HSA-GF, HMG-MPT and HMG-GF complexes. The binding processes between protein and drug molecules were exothermic and spontaneous owing to negative ∆H and ∆G values, respectively. The values of binding distance between protein and drug molecules were calculated from Förster resonance energy transfer theory. It was found from CD analysis that the bindings of MPT and GF drugs to HSA and HMG proteins altered the secondary structure of HSA and HMG proteins.


Further Validation of the Norwegian Self-Efficacy for Therapeutic Mode Use.
The Intentional Relationship Model (IRM) proposes six therapeutic modes as ways of relating to clients. The Norwegian self-efficacy for therapeutic mode use (N-SETMU) was found to have a one-component structure. However, its items reflect abstract concepts rather than concrete behaviors. To validate further the N-SETMU by linking its items to the Norwegian client assessment of modes (N-CAM), with 30 items constituting six scales (linked to each mode), possessing concrete, behavioral content. Occupational therapy students (n = 111) completed the N-SETMU and the N-CAM derived items, along with sociodemographic information. Component structure was analyzed with Principal Components Analysis (PCA), internal consistency of scales with Cronbach's α, and associations between scale scores with Pearson's r. All items on all N-CAM derived scales loaded on one latent component, except one item related to problem-solving. After removing this item, the scale functioned appropriately. Cronbach's α for all N-CAM derived scales ranged 0.88-0.94, and the associations between the N-CAM derived scales and the corresponding N-SETMU items ranged between 0.60 (advocating) and 0.79 (encouraging). In view of the strong associations between the concrete, N-CAM derived scales and the abstract N-SETMU items, this study supports the concurrent validity of the N-SETMU.


Plasma proteome analysis in diet-induced obesity-prone and obesity-resistant rats.
One of the major issues in the field of obesity is why some humans become obese and others resist development of obesity when exposed to high-calorie diets. Despite the same genetic background, namely obesity-prone (OP) and -resistant (OR) rats, differing responses have been demonstrated in a high fat diet-induced rodent model. The aim of the present study was to discover novel obesity-related biomarkers for susceptibility and/or resistance to obesity by proteomic analysis of OP and OR rat plasma. After feeding of high fat diet, OP rats gained approximately 25% more body weight than OR rats and were used for proteomic analysis using 2-DE combined with MALDI-TOF-MS. We categorized identified proteins into three groups by analysis of both average spot density in each group and individual spot density of six rats as a function of body weight. Consequently, category (1) included inter-α-inhibitor H4 heavy chain and fetuin B precursor, which can be used as novel plasma biomarkers for risk of obesity. Nine proteins of category (2) and (3) can also be plausible plasma markers in the study of obesity. This proteomic study is an important advancement over the previous steps needed for identification of OP and OR rats.


Interactions between traditional regional determinants and socio-economic status on dietary patterns in a sample of French men.
The aim of the present study was to assess the respective contributions of regional and socio-economic factors to dietary pattern. We used the data from the final MONICA (MONItoring of trends and determinants in Cardiovascular disease) population survey conducted in the three French centres in 1995-7 among a representative sample of 976 men aged 45-64 years. Dietary intake was assessed using a 3-d record method. Dietary patterns were identified by a factor analysis, based on fifteen food items. An analysis of variance was then used to study their relationship with regional and socio-economic determinants. Two major dietary patterns were identified: a 'Western diet', characterized by high intakes of sugar and sweets, grains, butter, added fats, eggs, potatoes and cheese; a 'prudent diet', mainly distinguished by high intakes of fruit, vegetables, olive oil and fish and low intakes of alcohol, high-fat meat and potatoes. Strong associations were mostly observed with the 'prudent diet' pattern, with a significant relationship with region, educational and income-tax levels, leisure-time physical activity and smoking status. There was also a statistically significant interaction between region and educational level (P=0.05), and between region and income-tax level (P=0.03), indicating that the influence of socio-economic factors is different among regions. In conclusion, these results indicate large regional and socio-economic differences in the dietary patterns of this French male population. When considering the 'prudent diet' pattern, they also suggest that traditional regional influences may now be overcome by socio-economic determinants.


Effect of Gender on the Outcome of Patients Receiving Immune Checkpoint Inhibitors for Advanced Cancer: A Systematic Review and Meta-Analysis of Phase III Randomized Clinical Trials.
Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p < 0.001 and HR 0.77, p < 0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p < 0.012), with the exception of melanoma (in women, HR 0.80, p = 0.006). PFS was longer in men than in women (HR 0.67, p < 0.001 and HR 0.77, p = 0.100, respectively). Conclusively, ICIs use was associated with more favorable outcomes in men, particularly for anti-CTLA-4 agents. In melanoma, not gender-related factors may influence the anti-tumor immune response evoked by ICIs.


[Cholecystocolic fistula: from symptoms to diagnosis].
We report 2 patients with a cholecystocolic fistula in whom diametrically opposite symptoms (isolated steator-rhea, jaundice and fever) were responsible for important clinical difficulties. These fistulae are far less common than cholecysto-duodenal fistulae. Endoscopic retrograde cholangiography was performed because of abnormal liver tests and led to diagnosis in both cases. Classical aerobilia was absent in both of our cases. Barium enema was disappointing (case n. 1), whereas technetium 99m scintiscan visualized the fistula (case n. 2). Two therapeutic approaches are possible in the case of cholecystocolic fistula. Surgery, usually combining cholecystectomy and extraction of common bile duct stones with the treatment of the fistula, may be performed systematically or in case of failure of sphincterotomy (case n. 1). On the other hand, endoscopical sphincteromy during endoscopic retrograde cholangiography, which, by reducing increased biliary pressure, may be sufficient to achieve spontaneous closure of the fistula in an elderly or high risk patient (case n. 2).


A taxonomic, functional, and phylogenetic perspective on the community assembly of passerine birds along an elevational gradient in southwest China.
Integrating multiple facets of biodiversity to describe spatial and temporal distribution patterns is one way of revealing the mechanisms driving community assembly. We assessed the species, functional, and phylogenetic composition and structure of passerine bird communities along an elevational gradient both in wintering and breeding seasons in the Ailao Mountains, southwest China, in order to identify the dominant ecological processes structuring the communities and how these processes change with elevation and season. Our research confirms that the highest taxonomic diversity, and distinct community composition, was found in the moist evergreen broadleaf forest at high elevation in both seasons. Environmental filtering was the dominant force at high elevations with relatively cold and wet climatic conditions, while the observed value of mean pairwise functional and phylogenetic distances of low elevation was constantly higher than expectation in two seasons, suggested interspecific competition could play the key role at low elevations, perhaps because of relative rich resource result from complex vegetation structure and human-induced disturbance. Across all elevations, there was a trend of decreasing intensity of environmental filtering whereas increasing interspecific competition from wintering season to breeding season. This was likely due to the increased resource availability but reproduction-associated competition in the summer months. In general, there is a clear justification for conservation efforts to protect entire elevational gradients in the Ailao Mountains, given the distinct taxonomic, functional, and phylogenetic compositions and also elevational migration pattern in passerine bird communities.


Optimizing Artificial Neural Network-Based Models to Predict Rice Blast Epidemics in Korea.
To predict rice blast, many machine learning methods have been proposed. As the quality and quantity of input data are essential for machine learning techniques, this study develops three artificial neural network (ANN)-based rice blast prediction models by combining two ANN models, the feed-forward neural network (FFNN) and long short-term memory (LSTM), with diverse input datasets, and compares their performance. The Blast_Weather_FFNN model had the highest recall score (66.3%) for rice blast prediction. This model requires two types of input data: blast occurrence data for the last 3 years and weather data (daily maximum temperature, relative humidity, and precipitation) between January and July of the prediction year. This study showed that the performance of an ANN-based disease prediction model was improved by applying suitable machine learning techniques together with the optimization of hyperparameter tuning involving input data. Moreover, we highlight the importance of the systematic collection of long-term disease data.


Hypobetalipoproteinemia with accumulation of an apoprotein B-like protein in intestinal cells. Immunoenzymatic and biochemical characterization of seven cases of Anderson's disease.
We describe here seven cases (from five kindreds) of Anderson's disease, which is characterized by diarrhea, steatorrhea, hypobetalipoproteinemia with low levels of cholesterol, triglycerides, and phospholipids, and failure to secrete chylomicrons after a fat meal. Enterocytes isolated from intestinal biopsies of patients after overnight fast showed numerous fat droplets, a histological picture resembling that of abetalipoproteinemia. Immunoenzymatic staining of the enterocytes demonstrated large amounts of material that reacted with a polyclonal antiserum to apolipoprotein B. Further, the immunoreactive material was found to react with several different monoclonal antibodies capable of recognizing both the B100 and B48 forms of apoprotein B, but not with any of several monoclonal antibodies capable of recognizing only B100. This suggests that the material in the enterocytes is the B48 form of apoprotein B or a fragment thereof. Additional findings included decreased low density lipoprotein levels with an abnormal chemical composition, abnormal high density lipoprotein2 (HDL2) and HDL3 particle size distributions, and an abnormal HDL apoprotein composition. Increased amounts of proteins having electrophoretic mobilities similar to apo E and the E-AII complex were present. Finally, some cases exhibited additional protein components of apparent molecular weights between 17,000 and 28,000, which was similar to some cases of abetalipoproteinemia. These findings demonstrate that Anderson's disease is not due to the absence of synthesis of intestinal apo B and suggest that it is more complex than previously thought, affecting all the lipoprotein classes.


The Epitope-Specific Anti-human CD4 Antibody MAX.16H5 and Its Role in Immune Tolerance.
T cell modulation in the clinical background of autoimmune diseases or allogeneic cell and organ transplantations with concurrent preservation of their natural immunological functions (e.g., pathogen defense) is the major obstacle in immunology. An anti-human CD4 antibody (MAX.16H5) was applied intravenously in clinical trials for the treatment of autoimmune diseases (e.g., rheumatoid arthritis) and acute late-onset rejection after transplantation of a renal allograft. The response rates were remarkable and no critical allergic problems or side effects were obtained. During the treatment of autoimmune diseases with the murine MAX.16H5 IgG1 antibody its effector mechanisms with effects on lymphocytes, cytokines, laboratory and clinical parameters, adverse effects as well as pharmacodynamics and kinetics were studied in detail. However, as the possibility of developing immune reactions against the murine IgG1 Fc-part remains, the murine antibody was chimerized, inheriting CD4-directed variable domains of the MAX.16H5 IgG1 connected to a human IgG4 backbone. Both antibodies were studied in vitro and in specific humanized mouse transplantation models in vivo with a new scope. By ex vivo incubation of an allogeneic immune cell transplant with MAX.16H5 a new therapy strategy has emerged for the first time enabling both the preservation of the graft-vs.-leukemia (GVL) effect and the permanent suppression of the acute graft-vs.-host disease (aGVHD) without conventional immunosuppression. In this review, we especially focus on experimental data and clinical trials obtained from the treatment of autoimmune diseases with the murine MAX.16H5 IgG1 antibody. Insights gained from these trials have paved the way to better understand the effects with the chimerized MAX.16H5 IgG4 as novel therapeutic approach in the context of GVHD prevention.


Longitudinal assessment of plasma androgen receptor copy number predicts overall survival in subsequent treatment lines in castration-resistant prostate cancer: analysis from a prospective trial.
Baseline plasma androgen-receptor copy number (AR-CN) is a promising biomarker for metastatic castration-resistant prostate cancer (mCRPC) outcome and treatment response; however, the role of its longitudinal testing is unproven. We aimed to evaluate the prognostic role of AR-CN assessed before subsequent treatment lines in mCRPC patients. A subgroup analysis of a prospective multicenter biomarker trial (IRSTB030) was carried out. Plasma AR-CN status (classified as normal or gain, cut-off value = 2) was assessed with digital PCR before each treatment line. Forty mCRPC patients receiving sequentially docetaxel, cabazitaxel and an AR signaling inhibitor (abiraterone or enzalutamide) were analyzed. At multivariate analysis, at each assessment overall survival (OS) was independently correlated with AR-CN status [first line: hazard ratio (HR) 4.1 [95% confidence interval (CI) 1.6-10.5]; second line: HR 2.4 (95% CI 1.1-5.3); third line: HR 2.1 (95% CI 1.0-4.3)] and median prostate-specific antigen [first line: HR 4.4 (95% CI 1.8-10.9); second line: HR 3.4 (95% CI 1.6-7.2); third line: HR 2.5 (95% CI 1.2-5.6)]. In the three subsequent assessments, AR-CN status changed from normal to gain in 15 (38%) patients. These patients had longer OS (47 months) compared with patients presenting AR-CN gain from first assessment (36 months), but shorter than those maintaining normal AR-CN (69 months) (P = 0.003). Plasma AR-CN correlates with survival not only at baseline (before first treatment), but also in the assessments before the following lines. Interestingly, AR-CN status may change from normal to gain across subsequent treatments in a significant number of cases, identifying a group of patients with intermediate outcomes. Longitudinal assessment of AR-CN status could represent a promising method to capture mCRPC intrinsic heterogeneity and to improve clinical management.


[Combined treatment of glyal and metastatic tumors of the brain].
Combined treatment of glyal and metastatic tumors of the brain allows prolongation of survival with the saved high physical and social level of the patients following the algorithm of the treatments: operative intervention with the minimal injury of the brain substance and preservation of all functionally important zones; chemotherapy with nitrosourea with the preferable bringing to the tumor zone; exposure to radiation.


A genetic-algorithm-aided stochastic optimization model for regional air quality management under uncertainty.
A genetic-algorithm-aided stochastic optimization (GASO) model was developed in this study for supporting regional air quality management under uncertainty. The model incorporated genetic algorithm (GA) and Monte Carlo simulation techniques into a general stochastic chance-constrained programming (CCP) framework and allowed uncertainties in simulation and optimization model parameters to be considered explicitly in the design of least-cost strategies. GA was used to seek the optimal solution of the management model by progressively evaluating the performances of individual solutions. Monte Carlo simulation was used to check the feasibility of each solution. A management problem in terms of regional air pollution control was studied to demonstrate the applicability of the proposed method. Results of the case study indicated the proposed model could effectively communicate uncertainties into the optimization process and generate solutions that contained a spectrum of potential air pollutant treatment options with risk and cost information. Decision alternatives could be obtained by analyzing tradeoffs between the overall pollutant treatment cost and the system-failure risk due to inherent uncertainties.


Persistence with non-selective NSAIDs and celecoxib among patients with gastroesophageal reflux disease and osteoarthritis or rheumatoid arthritis.
Gastrointestinal (GI) symptoms are common in patients taking nonselective, nonsteroidal anti-inflammatory drugs (nsNSAIDs) and are often a reason for therapy discontinuation. In osteoarthritis (OA) and rheumatoid arthritis (RA) patients requiring pain control, selective COX-2 NSAID use is typically associated with less dyspepsia than is nsNSAID use. Little is known about NSAID tolerance in patients with gastroesophageal reflux disease (GERD). This study assessed nsNSAID and celecoxib prescription patterns, in particular persistence, in OA/RA patients with concomitant diagnosis of GERD. An observational study of GERD patients with a diagnosis of OA/RA using two separate databases, the IMS Lifelink Health Plan Claims Database (PharMetrics) and Market Scan Claims Database (Medstat) was conducted. In each database, parallel and separate analyses were performed in adult patients who had their first GERD diagnosis in 2006 and who were subsequently diagnosed with OA or RA in the same year. From this subset of patients, celecoxib-naïve and nsNSAID-naïve cohorts were identified and patients were selected. Patients with pre-existing GI conditions were excluded from the study. Persistence, measured as time to discontinuation, was evaluated by Kaplan-Meier survival curves and Cox proportional hazards models. Reasons for discontinuations were not available in these databases. Fewer patients discontinued celecoxib as compared to nsNSAIDs during the 60 days of the first prescription and throughout the entire follow-up period. After adjusting for baseline characteristics, celecoxib patients still had significantly decreased risk of discontinuation as compared to nsNSAID patients (p < 0.0001). Replication of these observations in two separate, large patient databases increases the confidence in this study's conclusion. Limitations include those inherent to claims data analyses and retrospective review, e.g. these data do not provide clinical information related to reasons for medication discontinuation. In patients with concomitant GERD and OA or RA who require anti-inflammatory treatment, significantly more patients treated with celecoxib were persistent with their treatment than were patients treated with nsNSAIDs.


Functional and perceived benefits of wearing coloured filters by patients with age-related macular degeneration.
The aim was to investigate the visual effect of coloured filters compared to transmission-matched neutral density filters, in patients with dry age-related macular degeneration. Visual acuity (VA, logMAR), contrast sensitivity (Pelli-Robson) and colour vision (D15) were recorded for 39 patients (average age 79.1 ± 7.2 years) with age-related macular degeneration, both in the presence and absence of glare from a fluorescent source. Patients then chose their preferred coloured and matched neutral density transmission filters (NoIR). Visual function tests were repeated with the chosen filters, both in the presence and absence of glare from the fluorescent source. Patients trialled the two filters for two weeks each, in random order. Following the trial of each filter, a telephone questionnaire was completed. VA and contrast sensitivity were unaffected by the coloured filters but reduced through the neutral density filters (p < 0.01). VA and contrast sensitivity were reduced by similar amounts, following the introduction of the glare source, both in the presence and absence of filters (p < 0.001). Colour vision error scores were increased following the introduction of a neutral density filter (from 177.6 ± 60.2 to 251.9 ± 115.2) and still further through coloured filters (275.1 ± 50.8; p < 0.001). In the absence of any filter, colour vision error scores increased by 29.1 ± 55.60 units in the presence of glare (F2,107 = 3.9, p = 0.02); however, there was little change in colour vision error scores, in the presence of glare, with either the neutral density or coloured filters. Questionnaires indicated that patients tended to gain more benefit from the coloured filters. Coloured filters had minimal impact on VA and contrast sensitivity in patients with age-related macular degeneration; however, they caused a small reduction in objective colour vision, although this was not registered subjectively by patients. Patients indicated that they received more benefit from the coloured filters compared with neutral density filters.


Health related quality of life in sepsis survivors from the Prehospital Antibiotics Against Sepsis (PHANTASi) trial.
Due to the rise in incidence, the long term effect of sepsis are becoming more evident. There is increasing evidence that sepsis may result in an impaired health related quality of life. The aim of this study was to investigate whether health related quality of life is impaired in sepsis survivors and which clinical parameters are associated with the affected health related quality of life. We analyzed 880 Short Form 36 (SF-36) questionnaires that were sent to sepsis survivors who participated in the Prehospital Antibiotics Against Sepsis (PHANTASi) trial. These questionnaires were sent by email, 28 days after discharge. Data entry and statistical analyses were performed in SPSS. The data from the general Dutch population, was obtained from the Netherlands Cancer Institute (NKI-AVL) and served as a control group. Subsequently, 567 sepsis survivors were matched to 567 controls. Non-parametric Wilcoxon signed-rank test was performed to compare these two groups. Within the group, we sought to explain the diminished health related quality of life by factor analysis. We found that sepsis survivors have a worse health related quality of life compared to the general Dutch population. This negative effect was more evident for the physical component than the mental component of health related quality of life. We found that health related quality of life was significantly altered by advancing age and female sex. We also found that the total length of stay (in the hospital) and (previous) comorbidity negatively affect the physical component of health related quality of life. In our study we found that health related quality of life in sepsis survivors, 28 days after discharge, is severely diminished in comparison with the general Dutch population. The physical domain is severely affected, whereas the mental domain is less influenced. The length of stay, comorbidity, advancing age and female sex all have a negative effect on the Physical Component Scale of the health related quality of life.


Central actions of somatostatin in the generation and control of breathing.
The neuropeptide somatostatin is involved in many functions in the central nervous system as well as in the periphery. When it is centrally injected, an irreversible apnea is often developed. In the present review, we discuss the effects of somatostatin as the result of its actions at three levels of the respiratory neural network: a) by modulating the output of cranial or spinal motoneurons; b) by altering the genesis of the respiratory rhythm in the brainstem: and c) by regulating the chemosensory drive input into the respiratory pattern generator.


Imaging outcome measures for progressive multiple sclerosis trials.
Imaging markers that are reliable, reproducible and sensitive to neurodegenerative changes in progressive multiple sclerosis (MS) can enhance the development of new medications with a neuroprotective mode-of-action. Accordingly, in recent years, a considerable number of imaging biomarkers have been included in phase 2 and 3 clinical trials in primary and secondary progressive MS. Brain lesion count and volume are markers of inflammation and demyelination and are important outcomes even in progressive MS trials. Brain and, more recently, spinal cord atrophy are gaining relevance, considering their strong association with disability accrual; ongoing improvements in analysis methods will enhance their applicability in clinical trials, especially for cord atrophy. Advanced magnetic resonance imaging (MRI) techniques (e.g. magnetization transfer ratio (MTR), diffusion tensor imaging (DTI), spectroscopy) have been included in few trials so far and hold promise for the future, as they can reflect specific pathological changes targeted by neuroprotective treatments. Positron emission tomography (PET) and optical coherence tomography have yet to be included. Applications, limitations and future perspectives of these techniques in clinical trials in progressive MS are discussed, with emphasis on measurement sensitivity, reliability and sample size calculation.


The reliability and validity of a screening Questionnaire for 13 DSM-IV Axis I disorders (the Psychiatric Diagnostic Screening Questionnaire) in psychiatric outpatients.
The purpose of this study was to examine the reliability and validity of a new multidimensional screening instrument for 13 DSM-IV Axis I disorders. The Psychiatric Diagnostic Screening Questionnaire (PDSQ) is a 90-item self-administered questionnaire that screens for 13 DSM-IV disorders in 5 areas (eating, mood, anxiety, substance use, and somatoform disorders). A consecutive series of 500 psychiatric outpatients completed the PDSQ immediately before their intake evaluation. Seventy-four patients completed the scale a second time less than a week after the initial administration, and 51 patients completed a booklet of questionnaires that included established measures of the same symptom domains assessed by the PDSQ. The PDSQ subscales achieved moderate-to-high levels of internal consistency (mean Cronbach's alpha coefficient = 0.82) and test-retest reliability (mean correlation coefficient = 0.84). Subscale scores were significantly associated with blind clinical diagnoses, and individual PDSQ items correlated much more highly with their own subscale than with other subscales. The PDSQ subscales were much more highly correlated with established measures of the same symptom domain (mean correlation coefficient = 0.72) than with measures of other types of psychopathology (mean correlation = 0.17). The PDSQ is a reliable and valid measure of multiple DSM-IV disorders that is brief enough to be incorporated into routine clinical outpatient practice without disruption, yet lengthy enough to be a psychometrically sound instrument.


Molecular cloning and restriction endonuclease mapping of the murine cytomegalovirus genome (Smith Strain).
We have cloned EcoRI and HindIII fragments of the Smith strain of murine cytomegalovirus (MCMV) in the plasmid vector pACYC184. These cloned fragments were used to establish a restriction endonuclease map of the genome with respect to the EcoRI and HindIII sites. The map was constructed on the basis of data derived from cross-hybridizations of EcoRI and HindIII cloned fragments, double-digestions of the cloned fragments with EcoRI and HindIII, and hybridization of cloned HindIII fragments to Southern blots of MCMV DNA cleaved with EcoRI. From our mapping data, we have determined that the length of the MCMV genome is approximately 240 kbp. The genome does not appear to undergo inversions and lacks detectable repeated sequences. One HindIII cloned fragment was obtained which contained both HindIII termini. The existence of this fragment may be related to the mode of replication of the MCMV genome.


Sex Differences in Kappa Opioid Receptor Function and Their Potential Impact on Addiction.
Behavioral, biological, and social sequelae that lead to drug addiction differ between men and women. Our efforts to understand addiction on a mechanistic level must include studies in both males and females. Stress, anxiety, and depression are tightly linked to addiction, and whether they precede or result from compulsive drug use depends on many factors, including biological sex. The neuropeptide dynorphin (DYN), an endogenous ligand at kappa opioid receptors (KORs), is necessary for stress-induced aversive states and is upregulated in the brain after chronic exposure to drugs of abuse. KOR agonists produce signs of anxiety, fear, and depression in laboratory animals and humans, findings that have led to the hypothesis that drug withdrawal-induced DYN release is instrumental in negative reinforcement processes that drive addiction. However, these studies were almost exclusively conducted in males. Only recently is evidence available that there are sex differences in the effects of KOR activation on affective state. This review focuses on sex differences in DYN and KOR systems and how these might contribute to sex differences in addictive behavior. Much of what is known about how biological sex influences KOR systems is from research on pain systems. The basic molecular and genetic mechanisms that have been discovered to underlie sex differences in KOR function in pain systems may apply to sex differences in KOR function in reward systems. Our goals are to discuss the current state of knowledge on how biological sex contributes to KOR function in the context of pain, mood, and addiction and to explore potential mechanisms for sex differences in KOR function. We will highlight evidence that the function of DYN-KOR systems is influenced in a sex-dependent manner by: polymorphisms in the prodynorphin (pDYN) gene, genetic linkage with the melanocortin-1 receptor (MC1R), heterodimerization of KORs and mu opioid receptors (MORs), and gonadal hormones. Finally, we identify several gaps in our understanding of "if" and "how" DYN and KORs modulate addictive behavior in a sex-dependent manner. Future work may address these gaps by building on the mechanistic studies outlined in this review. Ultimately this will enable the development of novel and effective addiction treatments tailored to either males or females.


A conceptual framework for consciousness.
This article argues that consciousness has a logically sound, explanatory framework, different from typical accounts that suffer from hidden mysticism. The article has three main parts. The first describes background principles concerning information processing in the brain, from which one can deduce a general, rational framework for explaining consciousness. The second part describes a specific theory that embodies those background principles, the Attention Schema Theory. In the past several years, a growing body of experimental evidence-behavioral evidence, brain imaging evidence, and computational modeling-has addressed aspects of the theory. The final part discusses the evolution of consciousness. By emphasizing the specific role of consciousness in cognition and behavior, the present approach leads to a proposed account of how consciousness may have evolved over millions of years, from fish to humans. The goal of this article is to present a comprehensive, overarching framework in which we can understand scientifically what consciousness is and what key adaptive roles it plays in brain function.


Evaluation of success rates of immediate and delayed implants after tooth extraction.
To evaluate the success rates of immediate and delayed placement of implants with respect to the causes of tooth extraction and implant positions. A total of 310 dental implants (immediate implants:delayed implants = 76:234) were inserted into 80 patients. The types, sizes and positions of the implants and the causes of tooth extraction were recorded. We then investigated the relationship of implant loss with the causes of tooth extraction and placement methods. A higher failure rate was found for the implants in the posterior region of the maxilla, and when periodontitis was cited as a reason for tooth extraction. The overall success rates were 93.4% and 95.7% in the immediate and delayed implant placement groups, respectively, after a 2-year follow-up. No obvious relationship of success rate was observed with the implant placement method, cause of tooth extraction, and implants' position. The immediate placement of implants into fresh extraction sockets could offer advantages over the delayed implant placement. It seems to be a safe and predictable method for patients.


Outcome of allogeneic hematopoietic cell transplantation in patients with adult T-cell leukemia.
Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell neoplasm, and the outcome of patients with ATL after chemotherapy is poor. Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment modality for ATL, and four factors, namely, age > 50 years, male recipient, lack of complete remission at transplantation, and transplantation of cord blood, were previously shown to be associated with poor survival. We retrospectively analyzed the outcome of 21 patients with ATL who had undergone allo-HSCT at our hospital during a 3-year period. Of 21 patients, all had at least one of the above risk factors, and 18 had two or more. With a median follow-up of 19.7 months for living patients, the 1- and 2-year overall survival (OS) rates after transplantation were 34% and 27%, respectively. All relapse/progression events occurred within 1 year after allo-HSCT, and the cumulative incidence of relapse/progression at 1 year after allo-HSCT was 46.9%. The 100-day and 1-year nonrelapse mortality (NRM) rates were 19% and 42%, respectively. No significant difference in OS was observed between myeloablative and reduced-intensity conditioning regimens. The 3-year OS (27%) of ATL patients who received allo-HSCT and who had at least one adverse factor was somewhat poorer than the 3-year OS of 33% identified in a nationwide study of allo-HSCT in ATL patients in Japan. The high relapse/progression and NRM rates are major problems to be solved to achieve better outcome.


Recruitment and interaction dynamics of plant penetration resistance components in a plasma membrane microdomain.
Many fungal pathogens must enter plant cells for successful colonization. Barley mildew resistance locus o (Mlo) is required for host cell invasion upon attack by the ascomycete powdery mildew fungus, Blumeria graminis f.sp. hordei, and encodes the founder of a family of heptahelical integral membrane proteins unique to plants. Recessively inherited loss-of-function mutant alleles (mlo) result in effective penetration resistance to all isolates of the biotrophic parasite. We used noninvasive fluorescence-based imaging to show that fluorescently tagged MLO protein becomes redistributed in the plasma membrane (PM) and accumulates beneath fungal appressoria coincident with the initiation of pathogen entry into host cells. Polarized MLO accumulation occurs once upon attack and appears to be independent of actin cytoskeleton function. Likewise, barley ROR2 syntaxin, a genetically defined component of penetration resistance to B. graminis f.sp. hordei, and a subset of predicted PM-resident proteins become redistributed to fungal entry sites. We previously identified calmodulin, a cytoplasmic calcium sensor, as an interactor and positive regulator of MLO activity and demonstrate here by FRET microscopy an increase in MLO/calmodulin FRET around penetration sites coincident with successful host cell entry. Our data provide evidence for the formation of a pathogen-triggered PM microdomain that is reminiscent of membrane microdomains (lipid rafts) induced upon attempted entry of pathogenic bacteria in animal cells.


Hydrophobicity regained.
A widespread practice is to use free energies of transfer between organic solvents and water (delta G0transfer to define hydrophobicity scales for the amino acid side chains. A comparison of four delta G0transfer scales reveals that the values for hydrogen-bonding side chains are highly dependent on the non-aqueous environment. This property of polar side chains violates the assumptions underlying the paradigm of equating delta G0transfer with hydrophobicity or even with a generic solvation energy that is directly relevant to protein stability and ligand binding energetics. This simple regaining of the original concept of hydrophobicity reveals a flaw in approaches that use delta G0transfer values to derive generic estimates of the energetics of the burial of polar groups, and allows the introduction of a "pure" hydrophobicity scale for the amino acid residues.


Trends in immediate breast reconstruction and radiation after mastectomy: A population study.
In the last decade, there has been an increase in women undergoing immediate breast reconstruction (IBR) at the time of mastectomy. Recent literature suggests a shift in practice: Surgeons are becoming more comfortable with IBR in the setting of possible postoperative adjuvant radiotherapy, despite the known complications. This study sought to investigate, at a population level, the patient and surgeon characteristics associated with the use of IBR and which of these factors were predictive of adjuvant radiotherapy. This retrospective population-based cohort study included all adult women who underwent mastectomy in the province of Ontario from 2007 to 2014. The Canadian Institute for Health Information (CIHI) administrative data base was used to generate patient demographic and clinical data. The Ontario Health Insurance Plan (OHIP) data base was used to elicit surgeon characteristics including clinical experience and volume of practice dedicated to breast surgery. Outcome variables included reconstruction concurrent with mastectomy, alloplastic vs autologous reconstruction, and use of radiation. A total of 25 861 patients underwent mastectomy and 2972 had IBR (11.5%). The rate of IBR after mastectomy increased over time from 7.2% in 2007 to 17.2% in 2014 (P < .001). There was also an increase in the proportion of patients with IBR who received radiation over the time period, from 19.4% in 2007 to 28.2% in 2014 (P = .003). In the first regression analysis, IBR was associated with younger patient age, residing in closer proximity to cancer clinics, absence of malignant breast disease (ie, prophylactic mastectomy), having a younger surgeon performing the mastectomy, and receiving care at a teaching hospital. A second analysis showed that patient variables predictive of radiation after IBR were a younger age and a more advanced cancer stage and no variables specific to surgeon or institution were predictive of radiation in patients with IBR. A significant increase in the rate of IBR as well as the use of radiation occurred over the 7-year study period. Multiple patient and surgeon factors were associated with IBR. Variables associated with radiation in IBR were harder to predict. Given the increase in the use of radiation in IBR, further research is needed to look at long-term outcomes in these patients at the population level.


A role of piperine on monosodium urate crystal-induced inflammation--an experimental model of gouty arthritis.
In the present study, the anti-inflammatory effect of piperine was investigated on monosodium urate crystal-induced inflammation in mice, an experimental model for gouty arthritis, and compared it with that of the nonsteroidal anti-inflammatory drug, indomethacin. The levels of lysosomal enzymes, lipid peroxidation, tumor necrosis factor-α, and paw volume were increased significantly, and the activities of antioxidant status were in turn decreased in monosodium urate crystal-induced mice, whereas these changes were reverted to near normal levels upon piperine (30 mg/kg b.wt, i.p.) treatment. In vitro, piperine (50/100 ug/ml) suppressed the level of β-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated polymorphonuclear leucocytes in concentration-dependent manner when compared to control cells. Thus, the present study clearly indicated that piperine inhibit the monosodium urate crystal-induced inflammation and can be regarded as therapeutic drug for the treatment of acute gouty arthritis.


Holmium Laser Enucleation of the Prostate: Patient Selection and Outcomes.
Holmium laser enucleation of the prostate (HoLEP) is a proven technique to alleviate bladder outlet obstruction (BOO) from benign prostatic hyperplasia (BPH). Herein, we review factors relevant to selecting patients who will benefit from this procedure and expected outcomes. New randomized trials have validated the excellent outcomes achieved by HoLEP in the management of BOO from BPH. Its success has been reproduced in a diverse array of patients including those on anticoagulation, with detrusor underactivity/acontractility, prostate cancer, and in the retreatment setting. HoLEP can be applied to the majority of patients with BOO from BPH regardless of prostate size, previous operations, or the condition of the detrusor. HoLEP can also be carefully considered in patients requiring anticoagulation or who are undergoing active surveillance for low-risk prostate cancer. Immediate complication rate is low and incontinence is rare. Retrograde ejaculation occurs in approximately 75% patients. Furthermore, the retreatment rate for HoLEP is lower than reported for other endoscopic BPH procedures demonstrating its durability.


Imaging findings in posterior instability of the shoulder.
Posterior shoulder instability refers to the symptoms and signs resulting from excessive posterior translation of the humerus. Magnetic resonance (MR) imaging is the radiological modality of choice in the diagnostic assessment of posterior instability. Computed tomography (CT) is useful in the evaluation of osseous abnormalities associated with posterior instability. A detailed description of the posterior osseous and labroligamentous abnormalities has evolved recently, and many variant lesions of the posteroinferior labrum and/or capsular structures have been described. As the recommended surgical management of lesions associated with posterior instability is a lesion-specific approach, awareness of the specific lesions that have been described in association with posterior instability helps in pre-surgical planning. The purpose of this article is to review the classification of, and injury mechanisms leading to, posterior shoulder instability and to describe imaging findings associated with posterior instability, with emphasis on MR imaging.


Estrogen improves TIMP-MMP balance and collagen distribution in volume-overloaded hearts of ovariectomized females.
Our previous studies demonstrate that 17beta-estradiol limits chronic volume overload-induced hypertrophy and improves heart function in ovariectomized rats. One possible cardioprotective mechanism involves the interaction between estrogen, estrogen receptors, and proteins of the extracellular matrix (ECM). The impact of estrogen deficiency and replacement on left ventricular (LV) hypertrophy and ECM protein expression was studied using five female rat groups: intact sham-operated, ovariectomized sham-operated, intact with volume overload, ovariectomized with volume overload, and ovariectomized with volume overload treated with estrogen. After 8 wk, LV protein extracts were evaluated by Western blot analysis for matrix metalloproteinase-2 (MMP-2) and MMP-9, MT1-MMP, tissue inhibitors of MMPs (TIMP)-1, TIMP-2, TIMP-3 and TIMP-4, collagens type I and III, and estrogen receptor alpha and beta expression. MMP proteolytic activity was assessed by zymography. All volume-overloaded groups exhibited LV hypertrophy, which was associated with a loss of interstitial collagen and perivascular fibrosis. After 8 wk of volume overload, 70% of ovariectomized rats developed heart failure, in contrast to only one intact rat. A downregulation of MMP-2, estrogen receptor-alpha (ERalpha), and ERbeta, and upregulation of MMP-9 and MT1-MMP were found in the volume-overloaded hearts of ovariectomized rats. Estrogen treatment improved TIMP-2/MMP-2 and TIMP-1/MMP-9 protein balance, restored ERalpha expression, and prevented MMP-9 activation, perivascular collagen accumulation and development of heart failure. However, estrogen did not fully restore ERbeta expression and did not prevent the increase of MMP-9 expression or loss of interstitial collagen. These results support that estrogen limits undesirable ECM remodeling and LV dilation, in part, through modulation of ECM protein expression in volume-overloaded hearts of ovariectomized rats.


Development and validation of the LoVI: the Laws on Violence against women and girls Index.
Violence against women and girls (VAWG) is a human-rights violation with adverse long-term and inter-generational consequences. Redefining VAWG as legally unacceptable is one strategy for social change. The co-occurrence of national laws against VAWG is understudied, and tools to monitor the national legal environment are lacking. We developed the Laws on Violence against Women and Girls Index (LoVI) to measure global progress to develop comprehensive national legislation against child marriage, sexual harassment, domestic violence, and marital rape. Using data from 2016 and 2018 for 189 countries from the World Bank Women, Business, and the Law database, we used factor analysis to assess the dimensionality of the LoVI. We examined the distribution of the LoVI across countries and regions, and the relationship of national rankings on the LoVI with those for other indicators from the United Nations, Demographic and Health Surveys, and World Factbook. A single LoVI factor showed good model fit in the factor analysis. National LoVI rankings were positively associated with gender equality in human development and economic rights-related rankings and negatively associated with rates of justifying wife beating and of lifetime and prior-year physical and/or sexual IPV. The LoVI was not associated with national indicators for human development and income inequality. The LoVI is a concise, coherent, validated index to monitor the progress of nations on adopting comprehensive legislation to advance 2030 Sustainable Development Goal 5, to eliminate VAWG.


Effectiveness of a training program for enhancing therapists' understanding of the supportive-expressive treatment model for breast cancer groups.
This study evaluated a training program for leaders of supportive-expressive psychotherapy groups for breast cancer patients. Twenty-four mental health/medical cancer care professionals completed two training phases and were tested for their understanding of the treatment model. Participants' understanding was enhanced as a result of the training program. This study demonstrates that a brief training program can improve therapists' understanding of the treatment model and demonstrates an effective method of evaluation. Future research should examine how performance on these tests generalizes to performance when leading a supportive-expressive group.