Solely inhibin B producing ovarian tumour as a cause of secondary amenorrhoea with hot flushes: case report and review of literature.
In this report, we describe a case of a solely inhibin B producing fibrothecoma presenting with secondary amenorrhoea and hot flushes. Typical laboratory findings were an elevated LH, elevated inhibin B, low FSH and low estrogen. The World Health Organization classification of amenorrhoea was not applicable since the combination of low estrogen and low FSH suggested a central cause, whereas actually there was an ovarian cause. With staging laparotomy, a bilateral borderline tumour was detected in combination with a fibrothecoma. This report underpins the concept of inhibin B being a selective FSH secretion inhibitor of ovarian origin. Furthermore, a literature review on these topics is included.


Health risks of solid waste management practices in rural Ghana: A semi-quantitative approach toward a solid waste safety plan.
Inadequate solid waste management (SWM) can lead to environmental contamination and human health risks. The health risks from poor SWM can vary based on specific practices and exposure pathways. Thus, it is necessary to adequately understand the local context. This information, however, is rarely available in low-resource settings, particularly in rural areas. A solid waste safety plan could be helpful in these settings for gathering necessary data to assess and minimize health risks. As a step in developing such a tool, a semi-quantitative health risk analysis of SWM practices in nine Ghanaian rural villages was undertaken. Data on SWM in each village were collected through qualitative field observations and semi-structured interviews with local stakeholders. SWM-related health risks were assessed using the collected data, similar case studies in the scientific literature and dialogue among an assembled team of experts. The analysis identified context-specific practices and exposure pathways that may present the most substantial health risks as well as targeted solutions for mitigation risks. A risk assessment matrix was developed to quantify SWM risks as low, medium, high, or very high based on the likelihood and severity of identified hazards. The highest SWM risks were identified from dumpsites and uncontrolled burying of solid waste. More specifically, a very high or high risk of infectious and vector-borne diseases from SWM in the villages was identified, both in the disposal of solid waste in dumpsites and uncontrolled burying of solid waste. Additionally, a very high or high risk of inhalation, ingestion or dermal contact with contaminants was found in the disposal of solid waste in dumpsites, open burning of waste and reuse of waste from dumpsites as compost. The results demonstrate the potential value of a solid waste safety plan and a parsimonious approach to collect key local data to inform its contents.


Complications of endoscopic third ventriculostomy.
The treatment of choice for several types of obstructive hydrocephalus is endoscopic third ventriculostomy (ETV). However, in certain cases ETV is not clearly superior to shunt placement, and a question of choice arises. Apart from the possibility of success in each case, knowledge of complication rates is of major importance as well. Several series of ETVs have been published by various specialized centers. The reported overall complication rate is usually between 5% and 15%, and related permanent morbidity lower than 3%. The reported mortality of ETV is lower than 1%. The most frequent intraoperative complications of ETV are hemorrhage (the most severe being due to basilar rupture) and injury of neural structures. In the immediate postoperative period, hematomas, infections, and cerebrospinal fluid leaks may present. Morbidity can be neurological and/or hormonal. Systemic complications are related more to the patient's general status and less to the procedure itself. Late sudden deterioration, leading as a rule to a patient's death, has been reported. Its incidence is not exactly known, but probably is lower than 0.1%. Nevertheless, the severity of this complication necessitates alertness and informing the patient. The complication rate of ETV is low, and rarely is a reason for choosing shunt placement instead. However, as a method it requires considerable experience, and several studies report a relation of experience not only with success rates but also with complication avoidance.


De novo KIF1A mutations cause intellectual deficit, cerebellar atrophy, lower limb spasticity and visual disturbance.
Recently, de novo KIF1A mutations were identified in patients with intellectual disability, spasticity and cerebellar atrophy and/or optic nerve atrophy. In this study, we analyzed a total of 62 families, including 68 patients with genetically unsolved childhood cerebellar atrophy, by whole-exome sequencing (WES). We identified five de novo missense KIF1A mutations, including only one previously reported mutation (p.Arg316Trp). All the mutations are located in the motor domain of KIF1A. In all patients, initial symptom onset was during the infantile period, and included developmental delay in three patients and gait disturbance in two. Thereafter, they showed gait disturbances, exaggerated deep tendon reflexes, cerebellar symptoms and cerebellar atrophy on brain magnetic resonance imaging. Four patients showed lower limb spasticity, upper limb clumsiness and visual disturbances. Nerve conduction study revealed peripheral neuropathy in three patients. This study further delineates clinical features of de novo KIF1A mutations. Genetic testing of KIF1A should be considered in children with developmental delay, cerebellar atrophy and pyramidal features.


Impact of carbapenem-targeted antimicrobial stewardship interventions: an interrupted time-series analysis.
The development of carbapenem-resistant Gram-negative bacilli (CR-GNB) is largely favoured by indiscriminate and prolonged carbapenem use, which is a significant contributing factor. To evaluate the impact of two carbapenem antibiotic stewardship programme interventions on both carbapenem prescriptions and the clinical isolation rates of CR-GNBs, using interrupted time-series analysis. A time-series analysis was performed using data for carbapenem usage from a tertiary hospital in South Korea from January 2017 to July 2022. Two carbapenem antibiotic stewardship programme interventions were implemented sequentially: (i) a prospective audit and feedback (PAF) from November 2018 to April 2020 (intervention 1), and (ii) preauthorization from May 2020 to August 2020 (intervention 2). Monthly carbapenem usage and incidence of CR-GNB before and after each intervention were compared using an autoregressive integrated moving average model. Implementation of PAF resulted in a significant reduction in carbapenem consumption, followed by an additional decrease after the preauthorization was implemented. The incidence of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae increased after intervention 1, but there was a significant change from an increasing trend to a stationary trend after intervention 2. The incidence of carbapenem-resistant Pseudomonas aeruginosa, which had increased during the baseline period, became stationary after intervention 1. A significant decrease was observed in the incidence of carbapenem-resistant Acinetobacter baumannii during the implementation of intervention 1 and 2. This study emphasizes the importance of adopting comprehensive antibiotic management and rigorous infection control to prevent infections caused by antibiotic-resistant bacteria.


Determinants of fruit set in Yucca whipplei: Reproductive expenditure vs. pollinator availability.
The number of flowers produced by inflorescences of Yucca whipplei (Agavaceae) consistently exceeds the number of fruits produced by about one order of magnitude. To determine the factors responsible for low fruit set, the relation between pollinator availability, the amount of resources spent on reproduction (as indicated by inflorescence size), and the number of fruits matured was studied during 1978 and 1979 at 18 locations in chaparral, coastal sage scrub, and desert scrub communities of southern California.The following results support the conclusion that pollinators do not usually limit fruit production in Yucca whipplei. Rather, fruit production is limited by the amount of resources available to support developing fruits. (1) Fruit production is positively correlated with inflorescence size both within and between populations. The average size of inflorescence for a population is an excellent predictor of mean fruit production. Furthermore, 54% of the total variance in fruit production of individual plants can be explained by inflorescence size. (2) In contrast, although fruit production within most populations is positively correlated with an index of the number of pollinator visits to an inflorescence, the relative abundance of pollinators for a population is a poor predictor of mean fruit production, and only 9% of the total variance in fruit production can be explained by the visitation index. Furthermore, at four sites studied for two years, there was little change in average inflorescence size or fruit production from 1978 to 1979, despite large differences in relative abundance of pollinators at each of the sites. (3) Based on geographic proximity, and physiographic and vegetational similarities, study sites were grouped into regional clusters. Both inflorescence size and fruit production varied considerably between regions. Of the total variation in fruit production, 27% can be attributed to differences between regions. Most of this variation is the result of regional differences in inflorescence size, which in turn influence fruit production.Why does Yucca whipplei produce such large inflorescences if so few fruits can be supported? Two relevant hypotheses are discussed: (1) the floral display is the result of selection for pollen dissemination at the expense of fruit set; and (2) the floral display is the result of selection for a bet-hedging strategy either to increase the probability of adequate pollination when pollinators are unusually rare, or to allow individuals to support more fruits when resources are unusually abundant.


Taxonomy of the Quedius mukuensis group (Coleoptera: Staphylinidae: Staphylinini: Quediina) with descriptions of four new species from China.
Four new species of the subgenus Microsaurus Dejean, 1833 of the genus Quedius Stephens, 1829 are described based on specimens collected from China: Q. (Microsaurus) indigestus sp. nov., Q. (Microsaurus) purus sp. nov. and Q. (Microsaurus) rectus sp. nov. from Sichuan, and Q. (Microsaurus) medius sp. nov. from Hubei. The new species all belong to the Quedius mukuensis group, which is now increased to a total of 16 species. Line drawings and color illustrations of the adults, and the genitalia of the new species and some other ones are given. A key to all the species of this group is provided.


Long term performance characteristics of an electrochemical nitric oxide analyser.
The NIOX MINO(®) is a nitric oxide (FE(NO)) analyser based on electrochemical technology. It includes a replaceable sensor. Quality control procedures are recommended, but regular calibration is not possible. We aimed to evaluate the performance characteristics of the NIOX MINO(®) to identify if reproducibility changed over time, or with different sensors. Also, there are reports that reproducibility of FE(NO) may be reduced in patients with high FE(NO): our secondary aim was to address this issue. Reproducibility in 24 separate sensor-analyser units was calculated on three occasions over two months in 17 patients. These included 9 patients whose FE(NO) was high (mean 80 ppb) and 8 in whom FE(NO) was low (mean 16 ppb). One device failed quality control testing. For the remaining 23 sensor-analyser combinations, the mean coefficient of variation was 4.0% (range 1.2-7.2%) at baseline, 3.6% (range 2.0-7.0) at one month, and 3.6% (range 1.6-7.6%) at two months. The 95% C.I. for the mean limits of agreement for FE(NO) was ± 4.2 ppb (range 0.9-9.6 ppb), ± 3.8 ppb (range 1.6-6.9 ppb) and ± 3.2 ppb (range 1.2-6.8 ppb) respectively (NS). The limits of agreement exceeded the manufacturer's specifications (± 5 ppb) in 0 devices at baseline, 3 (13%) at one month, and 5 (22%) at two months. Reproducibility of FE(NO) using the NIOX MINO(®) was within clinically acceptable limits (± 10 ppb) and was generally stable. However, with time, a proportion of individual sensor-analyser combinations yielded variability outside the manufacturer's specifications.


Survival Benefit of Implantable-Cardioverter Defibrillator Therapy in Ambulatory Patients With Left Ventricular Assist Device.
Analysis of the prognostic effect of concomitant use of left ventricular assist devices (LVADs) and implantable -cardioverter defibrillators (ICDs) is lacking. The aim of this study is to define the survival effects of ICD therapy in ambulatory patients with LVAD. Patients with continuous-flow (cf) LVAD in a single tertiary center from December 2010 to May 2016 were retrospectively analyzed. Over a 6-year period, 257 patients had cf-LVAD implantation, 227 of them survived to discharge after the first month of LVAD implantation and were included in the study. The median follow-up time was 14 months, and 104 (45.8%) patients had ICD. One hundred and thirty-two (58.1%) patients were still under LVAD support at the end of the study period. Forty (17.6%) patients had heart transplantation, and 55 (24.2%) died. There was no significant difference between groups with ICD and without ICD for baseline characteristics except for higher pulmonary pressures and amiodarone use in the ICD group. Survival analysis showed significant survival benefit of ICD therapy (P = .02). After multivariate analyses including age, sex, left ventricular ejection fraction, and β-blocker usage, the benefit of ICD continued (hazard ratio: 0.54; 95% confidence interval, 0.303-0.975; P = .041). Ventricular arrhythmias (VAs) do not cause acute hemodynamic deterioration in patients with LVAD. However, VAs might be associated with poor prognosis. The present study showed that ICD therapy may improve survival among ambulatory patients with cf-LVAD-supported heart failure.


Association between ambient temperature and cardiovascular disease hospitalisations among farmers in suburban northwest China.
Cardiovascular disease (CVD) has become a severe public health and social issue in China. However, in northwest China, evidence on the association between ambient temperature and CVD hospitalisations in suburban farmers is somewhat limited. We collected CVD hospitalisations and meteorological data (2012-2015) in Zhangye suburbs and assessed the temperature-related risk and burden of admission by fitting a distributed lag nonlinear model to probe the relationship between ambient temperature and CVD hospitalisations among farmers in suburban northwest China. The results show that 23,921 cases of CVD admissions were recorded from 2012 to 2015. There was a "U-shaped" association between temperature and hospitalisations. Compared with the minimum admissions temperature (MAT) at 15.3 °C, the cumulative relative risk (RR) over lag 0-21 days was 1.369 (95% CI 0.980-1.911) for extreme cold temperature (1st percentile, -15 °C), 1.353 (95% CI 1.063-1.720) for moderate cold (5th percentile, -11 °C), 1.415 (95% CI 1.117-1.792) for extreme heat (99th percentile, 26 °C), and 1.241 (95% CI 1.053-1.464) for moderate heat (95th percentile, 24 °C). Female farmers were more susceptible to low and high temperatures than male farmers. Farmers aged ≥ 65 years old were more sensitive to low temperatures, while farmers aged < 65 years old were more sensitive to high temperatures. A total of 13.4% (3,208 cases) of the hospitalisation burden for CVD were attributed to temperature exposure, with the moderate range of temperatures accounting for the most significant proportion (12.2%). Ambient temperature, primarily moderate temperatures, might be an essential factor for cardiovascular-related hospitalisations among farmers in suburban northwest China.


Effect of dietary vitamin E on plasma lipids and atherogenesis in restricted ovulator chickens.
Restricted ovulator hens, which develop hyperlipidemia, were fed 1000 IU vitamin E per k of diet. These hens maintained their hyperlipidemia but plasma peroxide levels were reduced to those of laying hens. The intimal thickness of the aorta was measured by light microscopy. Hyperlipidemic hens which had high plasma peroxide levels had an increased intimal thickness as compared to laying hens. Hyperlipidemic hens which had their plasma peroxide levels reduced by dietary vitamin E had intimal thicknesses the same as laying hens. It is suggested that hyperlipidemia without lipid peroxidation either does not promote atherogenesis or does so at a reduced rate.


Paracetamol overdoses Paracetamol overdoses Fagan E Wannan G Reducing paracetamol overdoses. British Medical Journal . 1996 . 313 , 1417 - 1418 .
Medicines containing paracetamol are the most common cause of intentional drug overdose in Britain with about 70,000 cases of paracetamol overdose each year. Fortunately, death from overdose is fare - about 200 cases - Against a safety record of 30 million packs containing paracetamol sold each year.


Temporary cavernosal-cephalic vein shunt in low-flow priapism treatment.
Surgical shunting might be considered as the only option in the treatment of extended ischemic priapism that does not respond to aspiration and medication. A modified, simple, minimally invasive, and easily applicable artificial cavernosal-venous shunt technique for treating priapism is described in this report. A total of 15 patients with extended and nonresponsive low-flow priapism were treated with this technique between January 1998 and February 2007. When the conservative treatment of low-flow priapism does not yield the expected results, then the temporary cavernosal-cephalic vein shunt should be applied. The standard equipment required for this modified technique includes three angiocaths, two shorn blood serum sets, and saline solution with heparin. The blood in the cavernosa and the saline solution infusion are incorporated into the systemic circulation with the aid of serum sets and angiocaths. Priapism duration, history, causes, its relation with sexual stimulation, pain, and any prior management of priapism were assessed in all patients. A complete blood count and blood gases assessment were conducted in corporal aspirates, and duplex penile ultrasonography was performed, which showed attenuated blood flow in the cavernosal artery. This technique was applied in 15 patients. Complete detumescence was achieved in 13. In the two cases in whom the technique did not yield the expected results, there was a need for a sapheno-cavernosal shunt. These patients later complained of erectile dysfunction and penile pain that continued for 6 mo. Of the 13 patients in whom detumescence was achieved, 3 reported erectile dysfunction according to International Index of Erectile Function (IIEF) scores at the 12-mo follow-up. Artificial cavernosal-cephalic vein shunt in the treatment of priapism is simple, safe, effective, easily applicable, and warrants primary consideration when the second-line treatment of priapism is initiated.


Blastic NK-cell lymphoma expressing terminal deoxynucleotidyl transferase with Homer-Wright type pseudorosettes formation.
Rosette-forming malignant lymphoma is very rare. We report a blastic NK-cell lymphoma expressing terminal deoxynucleotidyl transferase (TdT) with formation of Homer-Wright type pseudorosettes. An 18-year-old boy presented with an enlarged inguinal lymph node. Histologically, the nodal architecture of the lymph node was diffusely effaced by small to medium sized monomorphic blastoid lymphoid cells which frequently formed Homer-Wright type pseudorosettes. Immunophenotyping of the tumour using immunohistochemistry and flow cytometry revealed LCA+, CD4+, CD56+, CD43+, TdT+, CD2-, cCD3-, CD8-, CD7-, CD34- and TIA-1-. DNA analysis revealed no gene rearrangement of TCR beta and gamma genes. In situ hybridization for EBER 1 & 2 was negative. No azurophilic granules were found in the Wright stain. Complete remission was achieved with six cycles of chemotherapy with the CHOP regimen. The disease recurred in the paranasal sinuses and bone marrow 2 years later. Immunophenotypic and genotypic similarities of the present case to those of TdT-negative blastic NK-cell lymphoma suggest that these diseases might be categorized as one entity irrespective of expression of TdT.


Syntheses and biological activities of daunorubicin analogs with uncommon sugars.
To study the effects of the sugar structure on the activity of anthracycline against cancer cells, six daunorubicin analogs containing different uncommon sugars were synthesized. Their cytotoxicities were tested against colon cancer cells by MTS assay. The results showed that the aglycon without sugar moiety has 70-100-fold lower activity against cancer cells than daunorubicin derivatives with various uncommon sugars. It suggests that the sugar structure in daunorubicin plays a critical role in determining its anticancer activity. In the compounds with various sugars, the 4'-OH of the sugar is an important determinant for their activity, while the axial-3'-substituent in the sugar interferes with the binding of daunorubicins to DNA. Therefore, 2,6-dideoxy sugars are a better choice for generating biologically active daunorubicin analogs than 6-deoxysugars, 2,3,6-trideoxysugars, or 2,3,4,6-tetradeoxysugars.


Intravenous immunoglobulin treatment for obstetric antiphospholipid syndrome refractory to conventional therapy: a single-arm and open-labelled multicentre clinical trial.
To compare the efficacy of intravenous immunoglobulin (IVIG) therapy for obstetric antiphospholipid syndrome (APS) refractory to conventional treatment. We conducted a single-arm and open-label multicentre clinical intervention trial. The enrolled criteria were patients with refractory APS who had a history of still or premature birth before 30 weeks of gestational age, even though they had been treated with conventional treatment, i.e., heparin and low-dose aspirin. After confirming the foetal heartbeats, a single course of IVIG (0.4 g/kg body weight daily for five days) was added to conventional treatment. The primary outcome was a live birth ratio of more than 30 weeks gestational period, and the secondary included improving pregnancy outcomes comparing to previous pregnancy. Twenty-five percent of the patients (2 of 8 cases) achieved a live birth after the 30th week of pregnancy by IVIG-only add-on treatment, which is the same prevalence as the historical control. However, by adding other second-line therapy to IVIG and conventional treatment, further three patients (37.5%) achieved improvements in pregnancy outcome compared to previous treatments. In total, five patients (62.5%) were able to achieve preferable pregnancy outcomes through combination treatment including IVIG. Our clinical trial could not demonstrate the efficacy of IVIG-only add-on therapy at improving the pregnancy outcomes of patients with obstetric APS refractory to conventional treatment. However, the combination of IVIG with rituximab or statins adding to conventional treatment improved pregnancy outcomes and resulted in more live births. Further studies are needed to investigate the efficacy of multi-targeted therapy to treat obstetric refractory APS.


[Pseudo-Kaposi's sarcoma secondary to superficial arteriovenous malformation: Stewart-Bluefarb syndrome].
Pseudo-Kaposi's sarcoma or Stewart-Bluefarb subtype acroangiodermatitis is uncommon and is caused by arteriovenous fistula and malformation. We report a new case. A 33-year-old man presented with painful red-violet plaque on the dorsum of the toes with angiomatous nodules on the sole. Histological and immunohistochemical studies for CD34 were consistent with Kaposi's sarcoma. Doppler ultrasonography and femoral angiography showed multiple distal arteriovenous shunts. Free-flow embolisation with fragments of Ethibloc gelatin sponge was performed and arteriography, performed immediately afterwards, showed delayed venous drainage. The outcome was good with complete drainage of the angiomatous lesions. Pseudo-Kaposi's sarcoma Stewart-Bluefarb subtype begins early in life in male subjects, with unilateral skin lesions. It bears clinical and histological resemblance to Kaposi's sarcoma. Doppler ultrasonography and angiography show arteriovenous fistulas that classically develop at shunts, explaining the role of traumatism and high vascular pressure in the genesis of this disease.


Clinical characteristics of prostate cancer in Japanese men in the eras before and after serum prostate-specific antigen testing.
We retrospectively reviewed a large series of Japanese men with histologically proven prostate cancer to assess the clinical characteristics of the cancer in three different eras of prostate cancer management since prostate-specific antigen (PSA) testing started in 1988. The medical records of 1125 patients treated between 1975 and 2002 were reviewed with respect to age, chief complaints, clinical stage, tumor grade, treatment options at each stage, and prognosis. We classified the patients as follows: those treated in the pre-PSA era between 1975 and 1988 (n=182), those treated in the PSA era between 1988 and 1997 (n=301; PSA era phase 1) and the PSA era between 1998 and 2002 (n=642; PSA era phase 2). Compared with the pre-PSA era, there were significant increases in the proportion of well-differentiated adenocarcinoma with respect to the biopsy tumor grade (24 vs 35%, P<0.01), in the proportion of linically organ-confined disease (21 vs 43%, P<0.001), and in the proportion of patients who underwent radical prostatectomy (13%vs 20%, P<0.01) after PSA testing was introduced. In addition, there was a significant difference in the proportion of subjects who were 70--79 years of age between the pre-PSA era (52%, 95/182) and the PSA era phase 2 (42%, 270/642, P<0.05). There was also a significant difference in the proportion of patients who underwent surgical castration between the pre-PSA era (78%) and PSA era phase 2 (10%, P<0.001). The proportion of patients participating in prostate cancer screening increased from 3% (pre-PSA era) to 11% (PSA era phase 1 and PSA era phase 2, P<0.05). In all clinical stages, there were significant differences between the pre- and post-PSA eras in cause-specific survival rates (5-year: 74 vs 94% in stages A and B, P<0.01; 54 vs 89% in stage C, P<0.001; 32 vs 53% in stage D, P<0.001). Migrations in the age of patients (toward younger patients), the stage of the cancer (towards earlier stages) and the histological findings (toward favorable findings), in addition to changes in treatment options, have contributed to the prolonged survival of Japanese men with prostate cancer after the PSA testing was introduced.


Evidence that antioxidants prevent the inhibition of Na+,K(+)-ATPase activity induced by octanoic acid in rat cerebral cortex in vitro.
The objective of the present study was to investigate the in vitro effects of octanoic acid, which accumulates in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and in Reye syndrome, on key enzyme activities of energy metabolism in the cerebral cortex of young rats. The activities of the respiratory chain complexes I-IV, creatine kinase, and Na+,K(+)-ATPase were evaluated. Octanoic acid did not alter the electron transport chain and creatine kinase activities, but, in contrast, significantly inhibited Na+,K(+)-ATPase activity both in synaptic plasma membranes and in homogenates prepared from cerebral cortex. Furthermore, decanoic acid, which is also increased in MCAD deficiency, and oleic acid strongly reduced Na+,K(+)-ATPase activity, whereas palmitic acid had no effect. We also examined the effects of incubating glutathione and trolox (alpha-tocopherol) alone or with octanoic acid on Na+,K(+)-ATPase activity. Tested compounds did not affect Na+,K(+)-ATPase activity by itself, but prevented the inhibitory effect of octanoic acid. These results suggest that inhibition of Na+,K(+)-ATPase activity by octanoic acid is possibly mediated by oxidation of essential groups of the enzyme. Considering that Na+,K(+)-ATPase is critical for normal brain function, it is feasible that the significant inhibition of this enzyme activity by octanoate and also by decanoate may be related to the neurological dysfunction found in patients affected by MCAD deficiency and Reye syndrome.


GPU-accelerated iterative reconstruction from Compton scattered data using a matched pair of conic projector and backprojector.
Iterative reconstruction from Compton scattered data is known to be computationally more challenging than that from conventional line-projection based emission data in that the gamma rays that undergo Compton scattering are modeled as conic projections rather than line projections. In conventional tomographic reconstruction, to parallelize the projection and backprojection operations using the graphics processing unit (GPU), approximated methods that use an unmatched pair of ray-tracing forward projector and voxel-driven backprojector have been widely used. In this work, we propose a new GPU-accelerated method for Compton camera reconstruction which is more accurate by using exactly matched pair of projector and backprojector. To calculate conic forward projection, we first sample the cone surface into conic rays and accumulate the intersecting chord lengths of the conic rays passing through voxels using a fast ray-tracing method (RTM). For conic backprojection, to obtain the true adjoint of the conic forward projection, while retaining the computational efficiency of the GPU, we use a voxel-driven RTM which is essentially the same as the standard RTM used for the conic forward projector. Our simulation results show that, while the new method is about 3 times slower than the approximated method, it is still about 16 times faster than the CPU-based method without any loss of accuracy. The net conclusion is that our proposed method is guaranteed to retain the reconstruction accuracy regardless of the number of iterations by providing a perfectly matched projector-backprojector pair, which makes iterative reconstruction methods for Compton imaging faster and more accurate.


Fe-Co bimetallic alloy nanoparticles as a highly active peroxidase mimetic and its application in biosensing.
This article presents a new enzyme-mimic activity of non-noble metal-based bimetallic Fe-Co NPs. This type of enzyme-mimic exhibits much higher affinity to H2O2 over other NPs-based peroxidase mimetics by at least one order of magnitude due to the synergistic effects between the two metals.


Tuning of Exchange Coupling and Switchable Magnetization Dynamics by Displacing the Bridging Ligands Observed in Two Dimeric Manganese(III) Compounds.
Two Mn(III)-based dimers, [Mn2(bpad)2(CH3O)4]n (1) and [Mn2(bpad)2(pa)2]n·2H2O (2) (Hbpad = N3-benzoylpyridine-2-carboxamidrazone, H2pa = phthalic acid), have been assembled from a tridentate Schiff-base chelator and various anionic coligands. Noteworthily, compound 1 could be identified as a reaction precursor to transform to 2 in the presence of phthalic acid, resulting in a rarely structural conversion process in which the bridges between intradimer Mn(III) ions alter from methanol oxygen atom with μ2-O mode in 1 (Mn Mn distance of 3.046 Å) to syn-anti carboxylate in 2 (Mn Mn distance of 4.043 Å), while the Mn(III) centers retain hexa-coordinated geometries with independently distorted octahedrons in two compounds. The dc magnetic determinations reveal that ferromagnetic coupling between two metal centers with J = 1.31 cm-1 exists in 1, whereas 2 displays weak antiferromagnetic interactions with the coupling constant J of -0.56 cm-1. Frequency-dependent ac susceptibilities in the absence of dc field for 1 suggest slow relaxation of the magnetization with an energy barrier of 13.9 K, signifying that 1 features single-molecule magnet (SMM) behavior. This work presents a rational strategy to fine-tune the magnetic interactions and further magnetization dynamics of the Mn(III)-containing dinuclear units through small structural variations driven by the ingenious chemistry.


Nine pairs of undescribed enantiomers from the resin of Styrax tonkinensis (Pierre) Craib ex Hart with anti-inflammatory activity.
Nine pairs of undescribed enantiomers, (±)-styraxoids A-I (1-9), were isolated from the resin of Styrax tonkinensis, and their structures were assigned by spectroscopic and computational methods. Compounds (±)-1 are a pair of degraded lignans, and the remaining compounds (±)-(2-9) are phenylpropanoid skeletons. Compounds (±)-8 and (±)-9 feature a 1,3-dioxolane moiety. The biological evaluation showed that both enantiomers of 1 could inhibit LPS-induced INOS and COX-2 in RAW264.7 cells in a dose-dependent manner.


Orthodox or traditional medicine? Private or public healthcare? Exploring treatment pathways for occupational health problems among informal automobile artisans.
Even though informal workers in developing countries have the most hazardous jobs, there is a sheer neglect for the treatment of their occupational health problems (OHP) in practice and by policies. This qualitative study explored how informal automobile artisans from Nigeria sought care for their OHP. It focused on their choice between orthodox and traditional medicine, between self-care and professional care, and between private and public health-care providers. 43 informal automobile artisans were purposively interviewed. The treatment sought depended on the type, the severity, and the perceived cause of the OHP. The distinction between rational and non-rational explanations of the causes of OHP usually determined the treatment endpoint. The financial means of the artisans and the cost of different treatments were also important factors. The study concluded that in order to develop safer working conditions in the sector, policy makers and artisanal associations should be aware of the considerations that informed the artisans' choices on how to treat OHP .


Direct sequencing of hepatitis A virus and norovirus RT-PCR products from environmentally contaminated oyster using M13-tailed primers.
Human norovirus (HuNoV) and hepatitis A (HAV) are recognized as leading causes of non-bacterial foodborne associated illnesses in the United States. DNA sequencing is generally considered the standard for accurate viral genotyping in support of epidemiological investigations. Due to the genetic diversity of noroviruses (NoV), degenerate primer sets are often used in conventional reverse transcription (RT) PCR and real-time RT-quantitative PCR (RT-qPCR) for the detection of these viruses and cDNA fragments are generally cloned prior to sequencing. HAV detection methods that are sensitive and specific for real-time RT-qPCR yields small fragments sizes of 89-150bp, which can be difficult to sequence. In order to overcome these obstacles, norovirus and HAV primers were tailed with M13 forward and reverse primers. This modification increases the sequenced product size and allows for direct sequencing of the amplicons utilizing complementary M13 primers. HuNoV and HAV cDNA products from environmentally contaminated oysters were analyzed using this method. Alignments of the sequenced samples revealed ≥95% nucleotide identities. Tailing NoV and HAV primers with M13 sequence increases the cDNA product size, offers an alternative to cloning, and allows for rapid, accurate and direct sequencing of cDNA products produced by conventional or real time RT-qPCR assays.


Receptors for insulin and epidermal growth factor-urogastrone in adult human fibroblasts do not change with donor age.
The ligand binding and biological responsiveness of cultured fibroblast monolayers were measured for porcine insulin and for murine epidermal growth factor--urogastrone in skin fibroblast cultures derived from young (22 to 31 years) and old (65 to 80 years) normal male volunteer donors. The receptor characteristics of the cells studied from the two groups of donors were not found to differ. In contrast with previous data, suggesting that there may be a genetically programmed aging of the insulin binding system, it is concluded that for both insulin and epidermal growth factor, receptor characteristics do not change with adult donor age.


Breaking the circulus vitiosus of neuroinflammation: Resveratrol attenuates the human glial cell response to cytokines.
Neuroinflammation is both cause and effect of many neurodegenerative disorders. Activation of astrocytes and microglia leads to the release of cytokines and reactive oxygen species followed by blood-brain barrier leakage and neurotoxicity. Transient neuroinflammation is considered to be largely protective, however, chronic neuroinflammation contributes to the pathology of Alzheimer's disease, multiple sclerosis, traumatic brain injury, and many more. In this study, we focus on the aspect of cytokine-induced neuroinflammation in human microglia and astrocytes. Here we show by mRNA and protein analysis that cytokines, released not only by microglia but also by astrocytes, lead to a circuit of proinflammatory activation. Moreover, we present how the natural compound resveratrol can stop the circuit of proinflammatory activation and facilitate return to resting conditions. These results will contribute to distinguishing between the causes and the effects of neuroinflammation, a better understanding of underlying mechanisms, and potential treatment options.


Unruptured Intracranial Aneurysms with Oculomotor Nerve Palsy : Clinical Outcome between Surgical Clipping and Coil Embolization.
To evaluate the clinical outcome of coil embolization for unruptured intracranial aneurysm (UIA) with oculomotor nerve palsy (ONP) compared with surgical clipping. A total of 19 patients presented with ONP caused by UIAs between Jan 2004 and June 2008. Ten patients underwent coil embolization and nine patients surgical clipping. The following parameters were retrospectively analyzed to evaluate the differences in clinical outcome observed in both coil embolization and surgical clipping : 1) gender, 2) age, 3) location of the aneurysm, 4) duration of the symptom, and 5) degree of ONP. Following treatment, complete symptomatic recovery or partial relief from ONP was observed in 15 patients. Seven of the ten patients were treated by coil embolization, compared to eight of the nine patients treated by surgical clipping (p = 0.582). Patient's gender, age, location of the aneurysm, size of the aneurysm, duration of symptom, and degree of the ONP did not statistically correlate with recovery of symptoms between the two groups. No significant differences were observed in mean improvement time in either group (55 days in coil embolization and 60 days in surgical clipping). This study indicates that no significant differences were observed in the clinical outcome between coil embolization and surgical clipping techniques in the treatment of aneurysms causing ONP. Coil embolization seems to be more feasible and safe treatment modality for the relief and recovery of oculomotor nerve palsy.


Effects of low-dose recombinant human insulin-like growth factor-I on insulin sensitivity, growth hormone and glucagon levels in young adults with insulin-dependent diabetes mellitus.
Despite recent interest in the therapeutic potential of recombinant human insulin-like growth factor-I (rhIGF-I) in the treatment of diabetes mellitus, its mechanism of action is still not defined. We have studied the effects of low-dose bolus subcutaneous rhIGF-I (40 microg/kg and 20 microg/kg) on insulin sensitivity, growth hormone (GH) and glucagon levels in seven young adults with insulin-dependent diabetes mellitus (IDDM) using a randomized double-blind placebo-controlled crossover study design. Each was subjected to a euglycemic clamp (5 mmol/L) protocol consisting of a variable-rate insulin infusion clamp (6:00 PM to 8:00 AM) followed by a two-dose hyperinsulinemic clamp (insulin infusion of 0.75 mU x kg(-1) x min(-1) from 8 to 10 AM and 1.5 mU x kg(-1) x min(-1) from 10 AM to 12 noon) incorporating [6,6 2H2]glucose tracer for determination of glucose production/utilization rates. Following rhIGF-I administration, the serum IGF-I level (mean +/- SEM) increased (40 microg/kg, 655 +/- 90 ng/mL, P < .001; 20 microg/kg, 472 +/- 67 ng/mL, P < .001; placebo, 258 +/- 51 ng/mL). Dose-related reductions in insulin were observed during the period of steady-state euglycemia (1 AM to 8 AM) (40 microg/kg, 48 +/- 5 pmol/L, P = .01; 20 microg/kg, 58 +/- 8 pmol/L, P = .03; placebo, 72 +/- 8 pmol/L). The mean overnight GH level (40 microg/kg, 9.1 +/- 1.4 mU/L, P = .04; 20 microg/kg, 9.6 +/- 2.0 mU/L, P = .12; placebo, 11.3 +/- 1.7 mU/L) and GH pulse amplitude (40 microg/kg, 18.8 +/- 2.9 mU/L, P = .04; 20 microg/kg, 17.0 +/- 3.4 mU/L, P > .05; placebo, 23.0 +/- 3.7 mU/L) were also reduced. No differences in glucagon, IGF binding protein-1 (IGFBP-1), acetoacetate, or beta-hydroxybutyrate levels were found. During the hyperinsulinemic clamp conditions, no differences in glucose utilization were noted, whereas hepatic glucose production was reduced by rhIGF-I 40 microg/kg (P = .05). Our data demonstrate that in subjects with IDDM, low-dose subcutaneous rhIGF-I leads to a dose-dependent reduction in the insulin level for euglycemia overnight that parallels the decrease in overnight GH levels, but glucagon and IGFBP-1 levels remain unchanged. The decreases in hepatic glucose production during the hyperinsulinemic clamp study observed the following day are likely related to GH suppression, although a direct effect by rhIGF-I cannot be entirely discounted.


[Stromal tumor of the prostate of uncertain malignant potential. A diagnostic rarity].
Stromal tumor of the prostate of uncertain malignant potential (STUMP) is an extremely rare entity. The clinical symptoms are nonspecific for this tumor. An abnormal digital rectal examination or an elevated prostate-specific antigen level is possible but not obligatory. The tumor has a high recurrence rate and could develop a sarcomatous dedifferentiation. Therapy varies from a wait-and-see approach to a radical prostatectomy. We report the case of a 74-year-old patient with a STUMP. Based on the case, the clinical, diagnostic, and therapeutic aspects of this rare tumor are discussed.


Local tumor regrowth after clinical complete response following neoadjuvant therapy for rectal cancer: what happens when organ preservation falls short.
Organ preservation strategies, especially watch and wait, after neoadjuvant treatment in locally advanced rectal cancer, have become topics that generate significant interest, for both patients and clinicians. The obvious advantage of these strategies is the avoidance of surgery with its associated risks and functional consequences. Over time, it has become evident that these strategies offer acceptable safety in oncological terms and, in most patients, allows preservation of the rectum without harming patients in terms of distant metastasis or survival. However, there is a small group of patients in whom the tumor returns after an initially diagnosed clinical complete response; patients with local tumor regrowth. The main threat in these patients is not simply local disease, which can be successfully managed in most cases, but the possible effects it may have on distant metastases. The pathophysiology of the phenomenon of local tumor regrowth is not well known and, therefore, strategies to minimize possible impact on survival are not well defined. Our aim is to review key issues in this subgroup that pose a substantial threat to the safety and viability of organ-preserving and watch-and-wait strategies. We also explore possible pathophysiologic explanations and future directions and perspectives that may improve both local and systemic disease control.


Patient quality of life and caregiver experiences in ovarian cancer: How are they related?
Patients with ovarian cancer and their spousal caregivers report similarities in health-related quality of life (HRQoL) and experiences throughout the cancer process. Previous research has reflected these shared experiences, demonstrating caregivers' capacity to accurately rate their patient-partner's HRQoL as a proxy. In response, this study examines associations between caregivers' perceptions of their patient-partner's HRQoL and their own caregiving responsibilities, consequences to well-being, and desired assistance from the healthcare system. This study will be beneficial when developing supports to assist caregivers throughout the cancer journey. Using a cross-sectional survey design, spousal caregivers (N = 82) of patients with ovarian cancer completed measures on perceived patient HRQoL and caregiver experiences. Correlation analyses determined medical and sociodemographic covariates. A multivariate multiple regression was conducted using four proxy HRQoL functioning subscales and three factors of reported experiences as caregivers in cancer. Post-hoc univariate regression analyses were run on significant factors to assess the associations that exist. Caregiver-perceived patient physical functioning was significantly associated with more caregiving tasks after controlling for education, age, and stage of ovarian cancer, but no other HRQoL functioning scale (i.e., role, emotional, social) was associated with caregiver experiences. The study provides a unique perspective into the caregiver experience by attending to interpersonal factors in relation to caregiver experiences. Results may be able to guide interventions aimed at supporting caregivers through the cancer process by offering more assistance with tasks as their partner's physical condition worsens.


A Dual-Output Single-Stage Regulating Rectifier With PWM and Dual-Mode PFM Control for Wireless Powering of Biomedical Implants.
This paper presents a reconfigurable, dual-output, regulating rectifier featuring pulse width modulation (PWM) and dual-mode pulse frequency modulation (PFM) control schemes for single-stage ac-to-dc conversion to provide two independently regulated supply voltages (each in 1.5-3 V) from an input ac voltage. The dual-mode PFM controllers feature event-driven regulation as well as frequency division. The former incorporates stable, fast, digital feedback loops to adaptively adjust the driving frequency of four power transistors, MP1∼4, based on the desired output power level to perform voltage regulation and deliver fast, transient, load currents. The latter sets the driving frequency of MP1∼4 to a user-defined fraction (1/1 ∼ 1/32) of the input frequency (1-10 MHz). The PWM controllers incorporate stable, analog, feedback loops to accurately adjust the conduction duration of MP1∼4 for voltage regulation and can be combined with PFM frequency division for an extended operation dynamic range. Fabricated in 0.18 μm 1P/6M CMOS, the regulating rectifier features power conversion efficiency (PCE) of >83.8% at 2 and 5 MHz, with the first output channel delivering ∼1 mW from VDD of 1.5 V and the second output channel delivering variable power from VDDH of 2.5 V to a load in the range of 0.1 to 1 kΩ. Peak PCE values of 90.75% (2 MHz, 100 Ω) and 90.7% (5 MHz, 200 Ω) are also measured. The regulating rectifier is suitable for the emerging modality of capacitive wireless power transfer to biomedical implants.


Ionizing radiation during pregnancy.
One of my patients had a computed tomography scan of her abdomen a week ago and has just found out she is 7 weeks pregnant. What should I tell her about the pregnancy and the risk to her fetus? Your patient is not at increased risk of miscarriage or major congenital fetal malformations due to radiation exposure. Her risk is similar to that of the general population (ie, 1% to 3%).


The use of animals in live-tissue trauma training and military medical research.
Uncontrolled hemorrhage is the most common preventable cause of death for soldiers wounded in combat. In live-tissue trauma training (LTTT), animals (mostly goats and pigs) are used to train physicians and paramedical personnel in how to treat severe traumatic injuries, including severe blood loss. Military personnel insist that such realistic training is necessary and has to date saved countless lives of soldiers. Animal rights groups, however, argue that the practice is inhumane and should be replaced with alternative methods. In this essay, the author explains how and why animals are used for LTTT and in military medical research (MMR), as well as why he feels that the continued use of animals for LTTT and MMR is justified. The author hopes to encourage wider discussion of this topic within the scientific, defense and animal welfare circles, leading to further refinements in the welfare and protection of animals used for these important, though often controversial, purposes.


Surgical technique arthroscopic posterior glenoidplasty for posterosuperior glenoid impingement in throwing athletes.
Posterosuperior glenoid impingement (PSGI) is the repetitive impaction of the supraspinatus tendon insertion on the posterosuperior glenoid rim in abduction and external rotation. While we presume the pain is mainly caused by mechanical impingement, this explanation is controversial. If nonoperative treatment fails, arthroscopic débridement of tendinous and labral lesions has been proposed but reportedly does not allow a high rate of return to sports. In 1996, we proposed adding abrasion of the bony posterior rim, or glenoidplasty. After arthroscopic assessment of internal impingement in abduction-extension-external rotation, extensive posterior labral and partial tendinous tear débridement is performed. Glenoidplasty involves recognition of a posterior glenoid spur and when present subsequent abrasion with a motorized burr. We retrospectively reviewed 27 throwing athletes treated between 1996 and 2008. Age averaged 27 years. CT arthrogram showed bony changes on the posterior glenoid rim in 21 shoulders. We evaluated 26 of the 27 patients at a minimum followup of 19 months (mean, 47 months; range, 19-123 months). Eighteen of the 26 patients resumed their former sport level. Six improved but had to change to an inferior sport level or another sport. Two patients did not improve after the procedure, one of whom changed sport practice. There were no complications or posterior instability. In the 15 patients who had radiographs at followup times from 20 to 87 months, we observed no arthritis or osteophyte. Comparison with an earlier series of soft tissue débridement shows glenoidplasty improves the likelihood of resuming a former sport level in patients with PSGI. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Analysis of medical services provided to patients with peripheral facial palsy in Korea: a descriptive, cross-sectional study of the health insurance review and assessment service national patient sample database.
This cross-sectional, retrospective, observational study analyzed the demographics of patients with peripheral facial palsy in South Korea and their use of healthcare services. The 2016 Korean Health Insurance Review and Assessment National Patient Sample dataset was used; a total of 4790 patients, diagnosed with facial palsy, who had used healthcare services at least once between January 2016 and December 2016 were included, and data on the use of medical services, hospitalizations, sociodemographic factors, treatments, and medications were analyzed. Overall, 326 patients per 100,000 individuals used healthcare services at least once because of peripheral facial palsy in 2016, with higher numbers for women and those aged 50-59 years. The percentage of patients who used Korean traditional medicine (KM), Western medicine (WM), and both KM and WM was 54.4, 23.3, and 22.3%, respectively. Users of both WM and KM had higher per capita medical costs, more visits, and longer treatment durations. Physiotherapy was the most frequent WM treatment (44.4%), and "examinations" was the costliest (24.7%) category. "Procedures" was both the most frequent and costliest KM category (99.9 and 57.3%, respectively). "Continuous intravenous injections" (8.6%) and "superficial heat therapy" (8.3%) were the most frequent WM treatments, while acupuncture accounted for 98% of all KM treatments. This study analyzed the demographic characteristics and medical service use of patients with peripheral facial palsy in detail. These results can be used as basic information to improve clinical and policy strategies for the management and treatment of peripheral facial palsy.


Analysis of human platelet antigen systems in a Moroccan Berber population.
The human platelet alloantigen systems HPA-1, -2, -3, -4, -5 and -6 in a Moroccan Berber population from the Amizmiz region were determined by polymerase chain reaction using sequence-specific primers (PCR-SSP). The gene frequencies obtained from these unrelated Berbers were 0 x 747 and 0 x 252 for HPA-1a and -1b; 0 x 817 and 0 x 182 for HPA-2a and -2b; 0 x 682 and 0 x 317 for HPA-3a and -3b; 1 and 0 x 0 for HPA-4a and -4b; 0 x 8616 and 0 x 1383 for HPA-5a and -5b; 1 and 0 x 0 for HPA-6a and -6b. The Berbers have the highest frequency for the 1b, 2b and 5b alleles of all the populations reported to date and also the lowest frequency for the 3b allele.


Methionine mediates resilience to chronic social defeat stress by epigenetic regulation of NMDA receptor subunit expression.
Previous studies suggested that methionine (Met) levels are decreased in depressed patients. However, whether the decrease in this amino acid is important for phenotypic behaviors associated with depression has not been deciphered. The response of individuals to chronic stress is variable, with some individuals developing depression and others becoming resilient to stress. In this study, our objective was to examine the effect of Met on susceptibility to stress. Male C57BL/6J mice were subjected to daily defeat sessions by a CD1 aggressor, for 10 days. On day 11, the behavior of mice was assessed using social interaction and open-field tests. Mice received Met 4 h before each defeat session. Epigenetic targets were assessed either through real-rime RTPCR or through Western Blots. Met did not modulate anxiety-like behaviors, but rather promoted resilience to chronic stress, rescued social avoidance behaviors and reversed the increase in the cortical expression levels of N-methyl-D-aspartate receptor (NMDAR) subunits. Activating NMDAR activity abolished the ability of Met to promote resilience to stress and to rescue social avoidance behavior, whereas inhibiting NMDAR did not show any synergistic or additive protective effects. Indeed, Met increased the cortical levels of the histone methyltransferase SETDB1, and in turn, the levels of the repressive histone H3 lysine (K9) trimethylation (me3). Our data indicate that Met rescues susceptibility to stress by inactivating cortical NMDAR activity through an epigenetic mechanism involving histone methylation.


Significance of caveolin-1 and matrix metalloproteinase 14 gene expression in canine mammary tumours.
Canine mammary tumours (CMTs) are the most common neoplasms affecting female dogs. There is an urgent need for molecular biomarkers that can detect early stages of the disease in order to improve accuracy of CMT diagnosis. The aim of this study was to examine whether caveolin-1 (Cav-1) and matrix metalloproteinase 14 (MMP14) are associated with CMT histological malignancy and invasion. Sixty-five benign and malignant CMT samples and six normal canine mammary glands were analysed using quantitative reverse transcription-polymerase chain reaction. Cav-1 and MMP14 genes were highly expressed in CMT tissues compared to normal tissues. Cav-1 especially was overexpressed in malignant and invasive CMT tissues. When a CMT cell line was cultured on fluorescent gelatin-coated coverslips, localisation of Cav-1 was observed at invadopodia-mediated degradation sites of the gelatin matrix. These findings suggest that Cav-1 may be involved in CMT invasion and that the markers may be useful for estimating CMT malignancy.


Immunomorphological localization of adenosine deaminase in rat tissues during ontogeny.
Immunomorphological methods were used to localize adenosine deaminase in tissues of the rat at different stages of ontogeny. In the thymus, lymphocytes began to express significant amounts of the enzyme with the appearance of demarcation between the cortex and medulla at 17 days of gestation. At any stage of ontogeny studied, strong adenosine deaminase staining was seen predominantly in cortical thymocytes. In the spleen and lymph node, the enzyme was initially detected in T cell areas, whereas primary follicles did not show positive adenosine deaminase staining. During further development, the enzyme was demonstrated in some lymphocytes of germinal centres and plasma cells. In the duodenum, epithelial cells of villi and the neck of crypts showed positive adenosine deaminase staining whereas no staining for the enzyme was observed in the epithelial cells of the base of crypts. Strongly positive staining for adenosine deaminase appeared in plasma cells of the lamina propria by four weeks after birth. The transient positive reaction for the deaminase could be recognized in epithelial cells of tubules of the kidney during late foetal and early postnatal development. The tubules of adult rats did not stain for the enzyme. In the cartilage of 15-day foetuses, positive adenosine deaminase staining was seen only in perichondrial cells and hypertrophic cells. Kupffer cells in the liver and endothelial cells of blood vessels stained positively for the enzyme at every stage of ontogeny studied.


How can we enhance undergraduate medical training in the operating room? A survey of student attitudes and opinions.
Teaching in the operating room (OR) may add substantial value to undergraduate medical education but at present, the value of this as a core-learning environment is unclear. We assessed student attitudes to see how the experience may be improved. All medical students from University of Leeds, UK were invited to complete an online-based questionnaire. The questionnaire gathered quantitative and qualitative responses relating to previous experiences, acquired benefits, and desired improvements. Students rated their overall satisfaction on a 10-point scale. A total of 292 students (20.8%) responded to the survey, out of whom 91.4% had previous OR experience. The median overall satisfaction was 7/10; 43.1% described bad or unfavorable experiences. Common themes included feeling intimidated, unwelcome, or ignored by staff, unrealistic expectations of knowledge, and poor or inadequate learning experiences. Benefits of attending the OR were improvements in scrub technique (82.3%), knowledge of anatomy (72.3%), anesthetics (67.5%), and surgical procedures (86.1%). Desired improvements included more opportunity to participate in the procedure (74.4%), encouragement from supervisors (73.6%), improved teaching (71.4%), and better induction to the OR environment (56%). Overall satisfaction of OR teaching is reasonable and many benefits are derived from attending the OR. However, bad experiences are common and this is detrimental to the student learning experience. The experience may be of increased value to undergraduate medical education within a dedicated and structured surgical teaching program.


Can single-cell and spatial omics unravel the pathophysiology of pre-eclampsia?
Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Characterised by the onset of hypertension and proteinuria in the second half of pregnancy, it can lead to maternal end-organ injury such as cerebral ischemia and oedema, pulmonary oedema and renal failure, and potentially fatal outcomes for both mother and fetus. The causes of the different maternal end-organ phenotypes of pre-eclampsia and why some women develop pre-eclampsia condition early in pregnancy have yet to be elucidated. Omics methods include proteomics, genomics, metabolomics, transcriptomics. These omics techniques, previously mostly used on bulk tissue and individually, are increasingly available at a single cellular level and can be combined with each other. Multi-omics techniques on a single-cell or spatial level provide us with a powerful tool to understand the pathophysiology of pre-eclampsia. This review will explore the status of omics methods and how they can and could contribute to understanding the pathophysiology of pre-eclampsia.


Two-Compartment Perfusion MR IVIM Model to Investigate Normal and Pathological Placental Tissue.
Perfusion and diffusion coexist in the placenta and can be altered by pathologies. The two-perfusion model, where f1 and, f2 are the perfusion-fraction of the fastest and slowest perfusion compartment, respectively, and D is the diffusion coefficient, may help differentiate between normal and impaired placentas. Investigate the potential of the two-perfusion IVIM model in differentiating between normal and abnormal placentas. Retrospective, case-control. 43 normal pregnancy, 9 fetal-growth-restriction (FGR), 6 small-for-gestational-age (SGA), 4 accreta, 1 increta and 2 percreta placentas. Diffusion-weighted-echo planar imaging sequence at 1.5 T. Voxel-wise signal-correction and fitting-controls were used to avoid overfitting obtaining that two-perfusion model fitted the observed data better than the IVIM model (Akaike weight: 0.94). The two-perfusion parametric-maps were quantified from ROIs in the fetal and maternal placenta and in the accretion zone of accreta placentas. The diffusion coefficient D was evaluated using a b ≥ 200 sec/mm2 -mono-exponential decay fit. IVIM metrics were quantified to fix f1 + f2 = fIVIM . ANOVA with Dunn-Sidák's post-hoc correction and Cohen's d test were used to compare parameters between groups. Spearman's coefficient was evaluated to study the correlation between variables. A P-value<0.05 indicated a statistically significant difference. There was a significant difference in f1 between FGR and SGA, and significant differences in f2 and fIVIM between normal and FGR. The percreta + increta group showed the highest f1 values (Cohen's d = -2.66). The f2 between normal and percreta + increta groups showed Cohen's d = 1.12. Conversely, fIVIM had a small effective size (Cohen's d = 0.32). In the accretion zone, a significant correlation was found between f2 and GA (ρ = 0.90) whereas a significant negative correlation was found between fIVIM and D (ρ = -0.37 in fetal and ρ = -0.56 in maternal side) and f2 and D (ρ = -0.38 in fetal and ρ = -0.51 in maternal side) in normal placentas. The two-perfusion model provides complementary information to IVIM parameters that may be useful in identifying placenta impairment. 2 TECHNICAL EFFICACY STAGE: 1.


How to improve adherence the captors of phosphorus on hemodialysis: Experience in real life with sucroferric oxyhydroxide.
The lack of adherence to phosphate -binders (PB) is the most important factor in not achieving the objectives of serum phosphorus (sP). Studies in the real-world population are needed to understand the influence of PBs on adherence and how to modify it. Prospective study conducted during 3 months in usual clinical practice. Out of 105 hemodialysis patients, 57 were switched to SFOH and 48 maintained their baseline treatment (control group). sP levels and the percentage of patients with sP levels <5mg/dl were compared. Adherence before and after introduction of SFOH, number of pills of PB, preferences in the administration mode and side effects were analyzed. The percentage of patients with controlled sP (<5mg/dl) increased significantly in the SFOH users' group (62.1-92.9%, p<0.001), but not in the control group (83-83.3%, p=NS). The average of daily tablets decreased significantly in the SFOH group (7.2-2.3 comp, p<0.001), but not in the control group (5.6-5.6, p=NS) and 100% of the patients used only one PB in SFOH group. The use of SFOH increased the adherence according to the SMAQ questionnaire (57.8-84.3%; OR 13.1, p<0.001). The possibility to choose the preferred mode of administration (split-swallowing 89% compared to chewing 11%), improved the acceptance (44.7-78%). 14% of the patients experienced side effects and in 5.2% SFOH was discontinued for this reason. SFOH controlled serum sP in 93% of patients, 100% in monotherapy, and with fewer tablets. The exploration and adaptation of preferences in the mode of administration influenced the acceptance of the drug by the patient and, probably, the future adherence.


The structure-based reaction mechanism of urease, a nickel dependent enzyme: tale of a long debate.
This review is an attempt to retrace the chronicle that starts from the discovery of the role of nickel as the essential metal ion in urease for the enzymatic catalysis of urea, a key step in the biogeochemical cycle of nitrogen on Earth, to the most recent progress in understanding the chemistry of this historical enzyme. Data and facts are presented through the magnifying lenses of the authors, using their best judgment to filter and elaborate on the many facets of the research carried out on this metalloenzyme over the years. The tale is divided in chapters that discuss and describe the results obtained in the subsequent leaps in the knowledge that led from the discovery of a biological role for Ni to the most recent advancements in the comprehension of the relationship between the structure and function of urease. This review is intended not only to focus on the bioinorganic chemistry of this beautiful metal-based catalysis, but also, and maybe primarily, to evoke inspiration and motivation to further explore the realm of bio-based coordination chemistry.


Genotype combinations of two IL4 polymorphisms influencing IL-4 plasma levels are associated with different risks of severe malaria in the Malian population.
We have previously found that children heterozygous for IL4 variable-number tandem repeat (VNTR) (rs8179190) or IL4-33 (rs2070874) variants were at risk for severe malaria (SM), whereas homozygous children were protected suggesting a complex genetic control. Hence, to dissect this complex genetic control of IL4 VNTR and IL4-33, we performed further investigation by conditional logistic regression analysis and found a strong interaction between both markers (p < 10(-6)). The best-fit model revealed three genotype combinations associated with different levels of SM risk. The highest risk (odds ratio (OR) = 4.8, 95% confidence interval (CI) = 2.0-11.5) was observed for subjects carrying at least one copy of both IL4-33 allele T and IL4 VNTR allele 1, who exhibited higher interleukin (IL)-4 plasma levels (p = 0.007). Children homozygous for IL4 VNTR allele 2 had a lower SM risk as well as lower IL-4 plasma levels. Our findings indicate that the genetic interaction between these two IL-4 variants is a key factor of SM susceptibility, probably because of its direct role in IL-4 regulation.


New species and records of Lycoriella Frey (Diptera, Sciaridae) from the Holarctic region.
The following species of the genus Lycoriella Frey sensu Vilkamaa Menzel from the Holarctic region are newly described and illustrated: Lycoriella ampla sp. n. (Canada: Ontario), L. barkalovi sp. n. (Russia: Krasnoyarsk region), L. canningsi sp. n. (Canada: British Columbia), L. eurystylata sp. n. (Canada: Quebec), L. excavata sp. n. (USA: Colorado), L. jakovlevi sp. n. (Russia: Karelia), L. kinbasketi sp. n. (Canada: British Columbia), L. longa sp. n. (USA: Colorado), L. nivicola sp. n. (Canada: Nunavut, NWT; Greenland), L. pearyi sp. n. (Greenland), L. taimyrensis sp. n. (Russia: Krasnoyarsk region) and L. tundrae sp. n. (Russia: Krasnoyarsk region). Lycoriella parva (Holmgren, 1869) is redescribed and illustrated and new faunistic records are given for some previously described species of Lycoriella. The newly described species raise the number of known species of Lycoriella from 38 to 50.


Comparative usefulness of cytology and peroxidase activity in conjunction with carcinoembryonic antigen levels for the diagnosis of mammary cancer.
Diagnosis of cancer via measurement of carcinoembryonic antigen (CEA) levels has been unreliable in early neoplastic stages. In order to improve diagnostic reliability, other cytological parameters were examined with CEA. Fifty specimens of effusion fluid were obtained from 40 hospitalized patients and the levels of CEA determined by radioimmunoassay in conjunction with application of an immunoperoxidase procedure. Simultaneous morphologic assessment was performed without knowledge of the immunoassay findings. In 8 documented cases of mammary cancer, all effusion fluid specimens had CEA levels of 16-1074 ng/ml, 7 cases had morphologically positive cells, but only 3 had a peroxidase positive reaction. Except for one case of ovarian papillary adenocarcinoma, the remaining patients were cancer free, had CEA levels of less than 15 ng/ml and only 2 cases (including the ovarian tumor patient) gave positive peroxidase responses. The presence of mammary metastatic duct carcinoma correlated 88% with CEA measurements but peroxidase response was not diagnostically helpful.


Single-channel monitoring of reversible L-type Ca(2+) channel Ca(V)α(1)-Ca(V)β subunit interaction.
Voltage-dependent Ca(2+) channels are heteromultimers of Ca(V)α(1) (pore), Ca(V)β- and Ca(V)α(2)δ-subunits. The stoichiometry of this complex, and whether it is dynamically regulated in intact cells, remains controversial. Fortunately, Ca(V)β-isoforms affect gating differentially, and we chose two extremes (Ca(V)β(1a) and Ca(V)β(2b)) regarding single-channel open probability to address this question. HEK293α(1C) cells expressing the Ca(V)1.2 subunit were transiently transfected with Ca(V)α(2)δ1 alone or with Ca(V)β(1a), Ca(V)β(2b), or (2:1 or 1:1 plasmid ratio) combinations. Both Ca(V)β-subunits increased whole-cell current and shifted the voltage dependence of activation and inactivation to hyperpolarization. Time-dependent inactivation was accelerated by Ca(V)β(1a)-subunits but not by Ca(V)β(2b)-subunits. Mixtures induced intermediate phenotypes. Single channels sometimes switched between periods of low and high open probability. To validate such slow gating behavior, data were segmented in clusters of statistically similar open probability. With Ca(V)β(1a)-subunits alone, channels mostly stayed in clusters (or regimes of alike clusters) of low open probability. Increasing Ca(V)β(2b)-subunits (co-)expressed (1:2, 1:1 ratio or alone) progressively enhanced the frequency and total duration of high open probability clusters and regimes. Our analysis was validated by the inactivation behavior of segmented ensemble averages. Hence, a phenotype consistent with mutually exclusive and dynamically competing binding of different Ca(V)β-subunits is demonstrated in intact cells.


Phytoremediation and long-term site management of soil contaminated with pentachlorophenol (PCP) and heavy metals.
Pentachlorophenol (PCP) is a persistent organic pollutant (POP) previously used as a timber treatment chemical to prevent sap stain and wood rot. Commonly used in wood treatment industries for the last 50 years, there are now many sites worldwide that are contaminated with PCP. Although persistent, PCP is a mobile contaminant and therefore has a propensity to leach and contaminate surrounding environments. Both willow (Salix sp., 'Tangoio') and poplar (Populus sp. 'Kawa') growing in an open-ended plastic greenhouse were found to tolerate soil PCP concentrations of 250 mg kg(-1) or less and both species stimulated a significant increase in soil microbial activity when compared to unplanted controls. Both poplar and willow could not survive PCP concentrations above 250 mg kg(-1) in soil. Pentachlorophenol degradation occurred in both planted and unplanted pots, but a higher rate of degradation was observed in the planted pots. Soil contaminated by wood-treatment activities often contains co-contaminants such as B, Cr, Cu and As, that are also used as timber preservatives. An additional column leaching experiment, done along side the potted trial, found that PCP, B, Cr, Cu and As were all present in the column leachate. This indicates that although Cu, Cr and As are generally considered immobile in the soil, they were mobilised under our column conditions. If a contaminated site were to be hydraulically 'sealed' using plants, a reticulation irrigation system should be installed to capture any contaminant leachate resulting from heavy rains. This captured leachate can either be independently treated, or reapplied to the site. Our data demonstrate a reduction in soil hydraulic conductivity with repeated application of leachate containing PCP and metal compounds but the soil did not become anaerobic. This would need to be considered in site remediation design.


Tea catechins enhance the mRNA expression of uncoupling protein 1 in rat brown adipose tissue.
The aim of the present study was to determine whether the antiobesity effects of tea catechins (TCs) are associated with the expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). Male Sprague-Dawley rats were fed a high-fat (HF; 35% fat) diet for 5 weeks, then divided into four groups and fed an HF, HF with 0.5% TC (HFTC), normal-fat (NF; 5% fat) or NF with 0.5% TC (NFTC) diet for 8 weeks. At the end of the experimental period, perirenal and epididymal white adipose tissues (WATs) and interscapular BAT were isolated. The NFTC group had significantly lower perirenal WAT weights than the NF group (NF: 12.7+/-0.53 g; NFTC: 10.2+/-0.43 g; P<.01), but the HF and HFTC groups did not differ significantly. TC intake had no effects on epididymal WAT weights. The NFTC and HFTC groups had significantly lower BAT weights than the NF and HF groups, respectively. The NFTC group had significantly higher UCP1 mRNA levels in BAT than the NF group (NF: 0.35+/-0.02; NFTC: 0.60+/-0.11; P<.05), but the HF and HFTC groups did not differ significantly. Thus, TC intake in the context of the NF diet reduced perirenal WAT weight and up-regulated UCP1 mRNA expression in BAT. These results suggest that the suppressive effect of TC on body fat accumulation is associated with UCP1 expression in BAT.


A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs.
Drugs that act at the N-methyl-D-aspartate (NMDA) receptor complex have the ability to terminate nerve agent-induced seizures and modulate the neuropathologic consequences of agent exposure. Drugs with mixed anticholinergic and anti-NMDA properties potentially provide an ideal class of compounds for development as anticonvulsant treatments for nerve agent casualties. The present experiment evaluated the potential NMDA antagonist activity of 11 anticholinergic drugs by determining whether pretreatment with the compound was capable of protecting mice from the lethal effects of NMDA. The following anticholinergic drugs antagonized NMDA lethality and are ranked according to their potency: mecamylamine > procyclidine = benactyzine > biperiden > trihexyphenidyl. The anticholinergics atropine, aprophen, azaprophen, benztropine, 3-quinuclidinyl benzilate (QNB), and scopolamine failed to show NMDA antagonist properties. In addition, and unexpectedly, diazepam, ethanol, and pentobarbital were also shown to be capable of antagonizing NMDA lethality over a certain range of doses. The advantages and limitations of using antagonism of NMDA lethality in mice as a bioassay for determining the NMDA antagonist properties of drugs are also discussed.


Molecular regulation of adult CNS neurogenesis: an integrated view.
Neural stem cells in the adult subventricular zone and dentate gyrus might be utilized to replace lost neurons in neurological disorders. The development of treatments would be facilitated by identifying the mechanisms that contribute to functional neurogenesis in adult animals. This review focuses on the emerging view that localized and overlapping pathways of growth factors, metalloproteases, neurotransmitters and hormones regulate different aspects of neurogenesis within the neurogenic niches. Neuroblast migration is precisely regulated by cooperation between several repellants, attractants and guidance molecules that are located within specific CNS regions. Further elucidation of crucial molecular regulators and integration of their signaling cascades should lead to more rational and effective approaches to harness the exciting phenomenon of adult CNS neurogenesis.


On-campus food purchasing behaviours and satisfaction of Australian university students.
Many university students have unhealthy dietary intake. The food environment on university campuses is a potentially important contributor to students' diet. This study aimed to describe on-campus food purchasing behaviours; satisfaction with the cost and availability of foods and beverages on-campus; and preferences for the on-campus food environment, in a sample of Australian university students. An online cross-sectional survey of 409 students at the University of Newcastle, Australia was conducted in 2017-2018. The survey assessed on-campus purchasing behaviours (frequency of purchase and expenditure), satisfaction with the cost and availability of foods, preferences for the on-campus food environment, and socio-demographics (eg age, domestic/international student). Results are reported as basic descriptive statistics. The majority of students (94%) purchased food or beverages on-campus, with 59% purchasing at least once per week. Satisfaction with the availability of foods was low (35.8% satisfied with the types of main meals available, and 48.5% for snacks); however, 72.8% were satisfied with types of beverages available. The majority of students were not satisfied with the cost of food and beverages (<40%). The top-rated preferences for changes to the on-campus food environment were healthier options, higher quality food, and cheaper food. Overall, the findings demonstrate strong support from students for healthier and cheaper food to be made available on-campus. SO WHAT?: There are two main factors of concern with regard to university food environments; the healthiness of food and beverage options and their cost. These should be key considerations of any future strategies aiming to improve university food environments.


Rate of spontaneous abortion after first trimester sonographic demonstration of fetal cardiac activity.
The incidence of spontaneous abortion once embryonic development has reached the stage of sonographically demonstrable cardiac activity has not been precisely determined in a large population. This retrospective study was designed to determine the risk of pregnancy loss after first trimester sonographic confirmation of fetal cardiac activity. A total of 840 patients were referred for ultrasound examination to the Perinatal Center, University of Cincinnati, between January 1, 1979 and December 31, 1985 who fulfilled the criteria of singleton pregnancy with sonographically visible fetal cardiac activity and crown-rump length consistent with gestational age less than or equal to 12 weeks. Patients were grouped into two categories based on the absence (control) or presence of vaginal bleeding (bleeding) prior to or at the time of the ultrasound examination. The abortion rates for the two groups were 5.2 and 16.4%, respectively (P less than 0.001). The relative risk of abortion in patients with vaginal bleeding was nearly four-fold greater than the control population. In the control group there was a significantly greater incidence of pregnancy loss in the greater than or equal to 34 years age group compared to less than 34 years age patients (4.4 versus 11.1%, P less than 0.05). Although there was no significant effect of race on abortion rates, low socioeconomic status almost doubled the relative risk of miscarriage. We conclude that the presence of visible fetal cardiac activity in the first trimester predicts a decreased risk for spontaneous abortion compared to generally reported rates. The significant risk factors for increased chance of abortion are vaginal bleeding, advanced maternal age, and low socioeconomic status.


No association between on-treatment platelet reactivity and bleeding events following percutaneous coronary intervention and antiplatelet therapy: A post hoc analysis.
Few studies have examined the relationship between the pharmacodynamics of antiplatelet drugs and the risk of clinically significant bleeding following percutaneous coronary intervention (PCI) for treating acute coronary syndrome (ACS). We examined the associations between the pharmacodynamics of prasugrel and clopidogrel and the incidence of bleeding events in the acute and chronic phases after PCI. We performed a post hoc analysis of the PRASFIT-ACS (PRASugrel compared with clopidogrel For Japanese patIenTs with ACS undergoing PCI) study of patients in whom platelet reactivity was determined as P2Y12 reaction units (PRU; VerifyNow® P2Y12 assay) or vasodilator-stimulated phosphoprotein-phosphorylation reactivity index (VASP-PRI). Japanese patients were randomized to prasugrel (loading/maintenance dose: 20/3.75 mg) or clopidogrel (300/75 mg), both in combination with aspirin, for 24-48 weeks. The bleeding outcome was a composite of major, minor, and clinically relevant bleeding. Overall, 66/685 (9.6%) and 65/678 (9.6%) of prasugrel- and clopidogrel-treated patients, respectively, experienced major, minor, or clinically relevant bleeding. PRU and VASP-PRI at 5-12h or in steady state conditions (at 4 weeks) were not associated with the risk of bleeding in the acute (to day 3) or chronic (from day 4 to 14 days after treatment discontinuation) phases of treatment, respectively. Less than 9% of patients with low on-treatment platelet reactivity (defined as PRU<85 or VASP-PRI<16) experienced bleeding events. No direct association of the pharmacodynamics of prasugrel and clopidogrel with the risk of bleeding was observed in this cohort of Japanese ACS patients following PCI.


Oxidation of hydroquinone by myeloperoxidase. Mechanism of stimulation by benzoquinone.
Myeloperoxidase (MPO) is a prime candidate for mediating the inflammatory tissue damage of neutrophils because it converts Cl- to the potent oxidant hypochlorous acid. It also oxidizes xenobiotics to reactive free radicals. We have found that the kinetics of oxidation of hydroquinone by myeloperoxidase are inadequately explained by the classical peroxidase mechanism. Peroxidation of hydroquinone displayed a distinct lag phase, which was practically abolished by excluding O2 and was eliminated by adding benzoquinone at the start of the reaction. Superoxide dismutase increased the rate of peroxidation by 40% but did not eliminate the lag phase. Spectral investigations revealed that during the initial phase of the reaction, MPO was converted to oxy-MPO, or compound III, by a mechanism that was not reliant on superoxide. Benzosemiquinone, however, was able to convert ferric-MPO to compound III. Both compound III and ferro-MPO reacted with benzoquinone to regenerate ferric-MPO. We propose that the lag phase occurs because benzosemiquinone reduces ferric-MPO to ferro-MPO, which rapidly binds O2 to form compound III. Since compound III is outside the peroxidation cycle, conversion of hydroquinone to benzoquinone is retarded. However, as benzoquinone accumulates, it oxidizes ferro-MPO and compound III to ferric-MPO, thereby increasing the rate of peroxidation. There is a minimal lag phase under an atmosphere of N2 because ferro-MPO would be rapidly oxidized by benzoquinone, without formation of compound III. We conclude that when substrates produce radicals capable of reducing ferric-MPO, they will be peroxidized efficiently only if oxy-MPO is readily recycled. Furthermore, these radicals will prevent MP3+ from reacting with H2O2, and thereby prevent the enzyme from oxidizing Cl- to hypochlorous acid. Thus, this mechanism could be exploited to prevent hypochlorous acid-mediated inflammatory tissue damage.


First Sampled High-Sensitive Cardiac Troponin T is Associated With One-Year Mortality in Sepsis Patients and 30- to 365-Day Mortality in Sepsis Survivors.
Previous studies using cardiac troponin levels to investigate the relationship between myocardial injury and mortality in sepsis patients have been conflicting. Our aim was to investigate the relationship between plasma high-sensitive cardiac troponin T (hs-cTnT) level and 30-day and 1-year mortality in sepsis patients and 30- to 365-day mortality in sepsis survivors. Sepsis patients requiring vasopressor support and admitted to our institution between 2012 and 2021 (n = 586) were included in this retrospective cohort study. Elevated hs-cTnT values (≥15 ng/L) were divided into quartiles (Q): Q1 15-35 ng/L; Q2 36-61 ng/L; Q3 62-125 ng/L; Q4 126-8630 ng/L. Stratified Kaplan-Meier curves and multivariable Cox regression were used for survival analyses. First sampled hs-cTnT was elevated in 529 (90%) patients. One-year mortality was 45% (n = 264). Increasing level of hs-cTnT was independently associated with higher adjusted hazard ratios (HR) for 1-year mortality compared with normal levels: Q1 HR 2.9 (95% confidence interval [CI], 1.03-8.1); Q2 HR 3.5 (95% CI, 1.2-9.8); Q3 HR 4.8 (95% CI, 1.7-13.4); Q4 HR 5.7 (95% CI, 2.1-16). In acute phase survivors, first sampled hs-cTnT was an independent predictor of 30- to 365-day mortality (HR 1.3; 95% CI, 1.1-1.6 per loge hs-cTnT). First sampled plasma hs-cTnT in critically ill sepsis patients was independently associated with 30-day and 1-year mortality. Importantly, first sampled hs-cTnT was associated with mortality during the convalescence phase (30- to 365-day) and could be a feasible marker to identify acute phase survivors at high risk of death.


Multi-dimensional visualisation of laboratory findings and functional test results for analysing the clinical course of disease in medicine.
The illustration of a patient's history by a graphical primitive is discussed. Illustration technology is presented which simultaneously represents quantitative examination findings (e.g., laboratory values) and qualitative findings (e.g., from function diagnostics) by a single geometrical figure. Depending on the medical results, this figure takes on characteristic forms which can be identified as patterns typical for a specific disease. The procedure developed is integrated in a user interface which is implemented in the form of a computerized medical record for use on a pentop computer. This portable computer assists the physician during ward rounds, supplies additional, intelligence-based information, serves quality control, and streamlines working procedures making them more efficient.


[Postoperative radiologic follow-up of rectocolonic anastomoses. The visualization of fistulous passages after evacuation].
The early postoperative study of colo-rectal anastomoses is a common diagnostic procedure with symptomatic patients which is extended to asymptomatic patients by some authors. Eighty-eight anastomotic fistulas were early diagnosed after intervention in 316 patients who underwent a water-soluble contrast enema. Four out of these fistulas (4.5%) could not be demonstrated at complete filling on X-ray, but were only opacified on radiographs taken after the spontaneous evacuation of contrast medium. The increase in endoluminal pressure due to the evacuation and the lack of balloon catheter probably play a role in allowing these fistulas to be visualized.


Risk factors for readmission among patients receiving outpatient parenteral antimicrobial therapy: a retrospective cohort study.
Background In the Netherlands, home treatment with intravenous antimicrobial therapy is a relatively new concept. Although several studies have shown that outpatient parenteral antimicrobial therapy (OPAT) can be administered safely, people receiving antimicrobials at home remain at risk for adverse events, including readmission. Aim The aim of our retrospective study was to identify risk factors for readmission in patients discharged with OPAT. Method Patients who were at least 18 years or older, discharged with OPAT between January 2016-December 2018 were included. Variables that were collected consisted of baseline demographics, complications, readmission within 30 days and treatment failure. Multivariate logistic regression analysis was performed to identify risk factors for readmission. Results A total of 247 patients were included; the most common reason for OPAT was bone and joint infections (17%). Penicillin (37%), cephalosporin (26%) and vancomycin/aminoglycoside (15%) were the most commonly prescribed antimicrobials. Among patients receiving medication subject to therapeutic drug monitoring (i.e. aminoglycosides or vancomycin), 51% (19/37) received weekly therapeutic drug monitoring. Receiving aminoglycosides or vancomycin (adjusted OR 2.05; 95% CI 1.30-3.25, p < 0.05) and infection of prosthetic material (adjusted OR 2.92, 95% CI 1.11-7.65, p < 0.05) were independent risk factors associated with readmission. Conclusion Although patients receiving medication subject to therapeutic drug monitoring are at higher risk of readmission, only half of the patients discharged with aminoglycosides or vancomycin were monitored according to IDSA guidelines. A specialized team in charge of monitoring patients with OPAT is more likely to increase the rate of monitoring to prevent readmissions and complications.


Ingestion of corrosive substances and the endoscopic role in assessing the severity of caustic injury.
The ingestion of caustic substances into the upper gastrointestinal tract is an unusual but potentially life-threatening problem. To evaluate the most commonly ingested corrosive substances, and the endoscopic findings, complications, and final outcomes of caustic intake. This cross-sectional study included 220 inpatient participants with corrosive poisonings during a 3-year period (2017-2019). Data from the national patient electronic system "My term" and from the "Poisoning information centre" at the University Clinic for Toxicology, Skopje were used. Demographic characteristics, type of corrosive substance, endoscopic findings by Kikendall classification, emerging complications, fatal outcome, and hospitalization were analysed. Data obtained were analysed with the SPSS software package, version 22.0 for Windows. During the period 2017-2019, out of 220 hospitalized cases with corrosive substance intake, 132 (60%) were with ingestion of acids, 19 (8.6%) with bases, 32 (14.6%) with bleaches, and 37 (16.8%) with other household products (p = 0.3469). The mean age of patients was 49.89 ±19.86 years. The most severe endoscopy findings (high-grade injury) were significantly more often associated with acid and base ingestion (p = 0.00001). Out of all strictures, 25 (64.1%) were on one location (either oesophagus or stomach), and 12 (30.8%) were on 2 locations. Upper gastrointestinal endoscopy is very important procedure for rapid assessment of severity of caustic injury, early appropriate therapy, as well as the potential development of strictures. The obtained data are very important for the development of a national program for the prevention of corrosive poisoning in our country.


Cyophiobiolins A-D, ophiobolin sestertepenoids from Cytospora rhizophorae.
Cyophiobiolins A-D, four unreported ophiobolin-type sesterterpenoids, were isolated from Cytospora rhizophorae A761, an endophytic fungus from Gynochthodes officinalis. The structures of these undescribed compounds were fully characterized on the basis of extensively spectroscopic data (1D, 2D NMR and HRESIMS) and single-crystal X-ray diffraction analyses. Moreover, cyophiobiolins A-D were evaluated for in vitro cytotoxic, anti-inflammatory, and antibacterial activities. Cyophiobiolins A-B showed inhibitory potency against lipopolysaccharide (LPS)-induced oxide production with IC50 values of 66.3 μM and 53.3 μM, respectively.


Role of the insulin/Tor signaling network in starvation-induced programmed cell death in Drosophila oogenesis.
Amino-acid starvation leads to an inhibition of cellular proliferation and the induction of programmed cell death (PCD) in the Drosophila ovary. Disruption of insulin signaling has been shown to inhibit the progression of oogenesis, but it is unclear whether this phenotype mimics starvation. Here, we investigate whether the insulin-mediated phosphoinositide kinase-3 pathway regulates PCD in mid oogenesis. We reasoned that under well-fed conditions, disruption of positive components of the insulin signaling pathway within the germline would mimic starvation and produce degenerating egg chambers. Surprisingly, mutants did not mimic starvation but instead produced many abnormal egg chambers in which the somatic follicle cells disappeared and the germline persisted. These abnormal egg chambers did not show an induction of caspases and lysosomes like that observed in wild-type (WT) degenerating egg chambers. Egg chambers from insulin signaling mutants were resistant to starvation-induced PCD, indicating that a complete block in insulin-signaling prevents the proper response to starvation. However, target of rapamycin (Tor) mutants did show a phenotype that mimicked WT starvation-induced PCD, indicating an insulin independent regulation of PCD via Tor signaling. These results suggest that inhibition of the insulin signaling pathway is not sufficient to regulate starvation-induced PCD in mid oogenesis. Furthermore, starvation-induced PCD is regulated by Tor signaling converging with the canonical insulin signaling pathway.


Serum inflammatory cell adhesion molecules predict malignant cerebral edema and clinical outcome early after mechanical thrombectomy in stroke.
Early prediction of life-threatening malignant cerebral edema (MCE) after mechanical thrombectomy (MT) is of clinical importance. Although inflammatory cell adhesion molecules (CAMs) and anti-inflammation factor Kruppel-like transcription factor (KLF) 4 are induced after acute ischemic stroke (AIS), the relationship between expressions of these molecules after MT and MCE as well as outcome in AIS patients have rarely been explored. We retrospectively reviewed the data of all AIS patients with large-vessel occlusion in anterior circulation who underwent MT from our stroke centers. The serum levels of CAMs and KLF4 were determined at 12 h after MT. MCE was assessed on follow-up head computed tomography within 5 days after MT. Of 91 included patients, 18 (19.8 %) patients experienced MCE. Patients with MCE were more likely to have higher levels of E-selectin and inter-cellular adhesion molecule 1 (ICAM-1) than those without MCE (P < 0.05). More specifically, elevated E-selectin, but not of vascular cell adhesion molecule 1 (VCAM-1), ICAM-1 and KLF4, was significantly associated with MCE after adjusting for hypertension, admission NIHSS, Alberta Stroke Program Early CT Scores, serum glucose, collateral circulation and onset to recanalization time respectively (P < 0.05). ROC curve suggested that E-selectin had considerable discrimination to predict MCE (AUC=0.7, 95 % CI: 0.55-0.83). Moreover, after adjusting by confounders, serum levels of E-selectin and ICAM-1 were independently associated with 3-month outcome in AIS patients after MT (both P < 0.05). These data indicate that of three CAMs, serum E-selectin level early after MT is the best predictor for MCE and outcome in AIS.


Purification and properties of detergent-solubilized pig kidney trehalase.
Trehalase (alpha, alpha-trehalase, EC 22.214.171.124) was solubilized from the brush border membrane of pig kidney cortex by Triton X-100 and sodium deoxycholate in the presence of inhibitors of proteolytic enzymes. The kidney enzyme was purified 3060-fold using gel filtration, ion exchange chromatography, Con A-Sepharose chromatography, phenyl-Sepharose CL-4B hydrophobic interaction chromatography, Tris-Sepharose 6B affinity chromatography, and hydroxylapatite chromatography. Tris-Sepharose 6B was utilized to absorb contaminant proteins. Purity was estimated as 99% or greater, based on amino-terminal amino acid analysis. The purified enzyme had a specific activity of 278 units/mg protein, showed one major band after silver staining, and had an estimated molecular weight of 80,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme was a glycoprotein and contained 2 mol of glucosamine per mole of trehalase. Kidney trehalase was inhibited by Tris, HgCl2, and phlorizin with Ki values of 3.8 mM, 11 microM, and 2.4 mM, respectively. Inclusion of Cl- in the reaction mixture protected the enzyme from inactivation by HgCl2. The apparent Km for trehalose was calculated to be 2.1 mM. Kidney trehalase was highly specific for trehalose and exhibited an optimal pH of 5.9. The isoelectric point was between pH 4.7 and 4.4, as measured by chromatofocusing.


Acquired lacrimal sac fistula mimicking basal cell carcinoma.
Lacrimal sac fistulae can arise after an episode of dacryocystitis, usually forming below the medial canthus. Preceding symptoms of a watery eye with mucous discharge and a history or signs of inflammation are typical. To highlight the features of lacrimal sac fistulae and encourage readers to consider this in the differential diagnosis of apparently ulcerative medial canthal skin lesions. We describe three patients with inferior-medial canthal ulcerative skin lesions, all referred to ophthalmic plastic surgeons either by dermatologists or plastic surgeons, presumed clinically to have basal cell carcinoma (BCC). All three were in fact due to acquired lacrimal sac fistulae, and syringing of the nasolacrimal system confirmed the presence of a fistula. These cases illustrate the importance of questioning patients about their previous ocular symptoms when dealing with less familiar periocular lesions.