Establishing physico-chemical reference conditions in Mediterranean streams according to the European Water Framework Directive.
Type-specific physico-chemical reference conditions are required for the assessment of ecological status in the Water Framework Directive context, similarly to the biological and hydro-morphological elements. This directive emphasises that natural variability of quality elements in high status (reference condition) needs to be quantified. Mediterranean streams often present a marked seasonal pattern in hydrological, biological and geochemical processes which could affect physico-chemical reference conditions. This study establishes general physico-chemical reference conditions (oxygenation, nutrient, salinity and acidification conditions) for different Mediterranean stream types. 116 potential reference sites located in 23 Mediterranean catchments in Spain were sampled in spring, summer and autumn in 2003. All sites were subjected to a screening method for the selection of reference sites in Mediterranean streams (Mediterranean Reference Criteria) and classified using a pre-established stream typology that establishes five different stream types (temporary streams, evaporite-calcareous at medium altitude, siliceous headwaters, calcareous headwaters and large watercourses). Reference conditions (reference value and reference threshold equivalents to high-good class boundary) were calculated using two different methods according to the availability of reference sites: the reference site 75th percentile approach of all reference sites and the 25th percentile of the population approach. The majority of the studied potential reference sites (76 out of 116) were selected as reference sites. Regarding type-specific reference conditions, only siliceous headwaters could be considered different from the rest of stream types because lower conductivity and pH. All reference stream types presented seasonal differences as regards some parameters, except for temporary streams due to the high natural variation of this stream type. For those parameters which presented seasonal differences in a specific stream type, the least restrictive values were proposed as reference conditions.


The radiosensitivity of chromosomes of rabbit lymphocytes.
Dicentrics were induced in human and rabbit lymphocytes in vitro by exposure to X-irradiation. The yields were compared with data reported in the literature. To elucidate the reasons for the different findings we have evaluated the parameters for the different models by maximum likelihood methods. From this analysis it can be concluded that the earlier claim of Bajerska and Liniecki [1] that both species have the same radiosensitivity must be discounted, and that their similarity was due to the abnormally low values these investigators observed in irradiated human lymphocytes.


Effects of root herbivory by an insect on a foliar-feeding species, mediated through changes in the host plant.
The effects of root herbivory by larvae of the scarabaeid, Phyllopertha horticola, on the growth of Capsella bursa-pastoris were examined. Individuals of Aphis fabae were reared on the leaves to determine what effect, if any, root feeding has on the performance of this insect. The experiment was conducted under two watering regimes ('low' and 'high'). Low watering and root feeding caused water stress in the plants and this was reflected in a reduction in vegetative biomass and an increase in the proportion of material allocated to reproduction. Supplying plants with ample water in the 'high' treatment enabled the water stress caused by root herbivory to be offset, but not completely overcome. Low watering and root feeding caused an increase in aphid weight and growth rate, while root feeding also increased fecundity and adult longevity. These effects are attributed to an improvement in food quality, measured by total soluble nitrogen, and caused by amino acid mobilization due to the water stress. The implications of these results in agricultural and ecological situations are discussed.


Online MR guided dose escalated radiotherapy for organ preservation in distal rectal cancer.
Non-surgical management of rectal cancer aiming for organ-preservation is an important development to improve rectal cancer treatment. Dose escalated radiotherapy represents one approach to increase clinical complete response (cCR) rates. In the present study we present feasibility and outcome data on rectal cancer patients who were treated with dose escalated radiotherapy using an MR guided online response-adaptive workflow. A total of five patients were treated with 45 Gy in 25 fractions to the mesorectum and the internal iliac lymph nodes and a simultaneous integrated boost to the primary tumor with 50 Gy in 25 fractions on a conventional linac. In addition, weekly response-adaptive boost fractions with 3 Gy per fraction were scheduled on a 1.5 T MR-Linac. Concomitant chemotherapy with 5-fluorouracil was given as continuous venous infusion during the first and last week of treatment. Response was evaluated approximately-three months after the end of treatment and surgery was omitted in case of a clinical complete response (cCR) or a near cCR. Toxicity was graded by using PRO-CTCAE, Quality of life by the EORTC-QLQ-C30 questionnaire and continence according to the Wexner scale. Response-adaptive dose escalated radiotherapy was feasible and well tolerated by all patients. Four reached a clinical complete response, one had a local excision confirming pathological complete response (pCR). All PRO-CTCAE grade 3 toxicities resolved within six months after the end of treatment. Quality of life and continence scores during follow-up were comparable to baseline levels. Dose-escalated online response-adaptive MR-guided radiotherapy appears to be a very promising treatment with the goal of organ preservation in rectal cancer leading to high response rates, excellent organ function and limited side effects. Further prospective evaluation is needed.


Turning anti-ageing genes against cancer.
Recent studies in diverse organisms implicate proto-oncogenic pathways, including insulin-like growth factor-I (IGF-I), Ras and AKT/protein kinase B in the ageing process. Although IGF-I is thought to contribute to cancer by promoting growth and preventing apoptosis, evidence from model organisms suggests that proto-oncogene homologues might contribute to the DNA mutations and chromosomal damage that are observed in tumour cells by increasing DNA damage, in both dividing and non-dividing cells, and involving error-prone systems in DNA repair. This raises the possibility that cancer can be reduced by chronic downregulation of pro-ageing pathways.


A scoping methodological review of simulation studies comparing statistical and machine learning approaches to risk prediction for time-to-event data.
There is substantial interest in the adaptation and application of so-called machine learning approaches to prognostic modelling of censored time-to-event data. These methods must be compared and evaluated against existing methods in a variety of scenarios to determine their predictive performance. A scoping review of how machine learning methods have been compared to traditional survival models is important to identify the comparisons that have been made and issues where they are lacking, biased towards one approach or misleading. We conducted a scoping review of research articles published between 1 January 2000 and 2 December 2020 using PubMed. Eligible articles were those that used simulation studies to compare statistical and machine learning methods for risk prediction with a time-to-event outcome in a medical/healthcare setting. We focus on data-generating mechanisms (DGMs), the methods that have been compared, the estimands of the simulation studies, and the performance measures used to evaluate them. A total of ten articles were identified as eligible for the review. Six of the articles evaluated a method that was developed by the authors, four of which were machine learning methods, and the results almost always stated that this developed method's performance was equivalent to or better than the other methods compared. Comparisons were often biased towards the novel approach, with the majority only comparing against a basic Cox proportional hazards model, and in scenarios where it is clear it would not perform well. In many of the articles reviewed, key information was unclear, such as the number of simulation repetitions and how performance measures were calculated. It is vital that method comparisons are unbiased and comprehensive, and this should be the goal even if realising it is difficult. Fully assessing how newly developed methods perform and how they compare to a variety of traditional statistical methods for prognostic modelling is imperative as these methods are already being applied in clinical contexts. Evaluations of the performance and usefulness of recently developed methods for risk prediction should be continued and reporting standards improved as these methods become increasingly popular.


The management of depression following traumatic brain injury: A systematic review with meta-analysis.
Traumatic brain injury (TBI) is prevalent. Declining mortality has led to increasing survivors with chronic sequalae, including depression. With a lack of guidelines, this review aims to provide a comprehensive, evidence-based summary of the management of depression following TBI. Systematic searches were conducted for quasi-experimental and randomized controlled trials (RCTs) assessing pharmacotherapy, psychological interventions, and transcranial magnetic stimulation (TMS). Databases searched CENTRAL, Medline, Embase, CINAHL, PsycINFO, Web of Science, and ProQuest dissertations. Data extraction and risk-of-bias tools were used. Where possible, outcomes were combined into meta-analyses. 2719 studies were identified. After abstract screening and full-text reading, 34 remained. Prophylactic sertraline significantly reduced the odds of depression (OR (odds ratio) = 0.31 [95%CI (confidence interval) = 0.12 to 0.82]). Meta-analysis of RCT's showed TMS to have the greatest reduction in depression severity (SMD (Standardized-Mean-Difference) = 2.43 [95%CI = 1.24 to 3.61]). Stimulants were the only treatment superior to control (SMD = -1.03 [95%CI = - 1.6 to -0.47]). Methylphenidate was the most effective pharmacotherapy. Sertraline appears effective for prevention. The efficacy of psychological interventions is unclear. TMS as a combination therapy appears promising. Heterogeneity of study populations and dearth of evidence means results should be interpreted cautiously.


[Morphological study of congenital osteopetrosis in op rats].
Osteopetrosis appears spontaneously on the "op" rat (Fatty/ORL). At the confirmed stage, description of histologic lesions is made. The attention is attracted by an endocavitary tissue observed at later stage of disease. This one does not seem to be the result of a metaplasia but rather the image of a persistent osteoblastic activity.


Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy.
Seizure exacerbation in catamenial epilepsy (CE) is associated with the decrease in progesterone secretion and increase in estradiol secretion during the premenstrual period. Moreover, experimental evidence suggests that tetrahydrodeoxycorticosterone (THDOC), a positive modulator of the type A receptor for gamma-aminobutyric acid (GABA), and dehydroepiandrosterone sulfate (DHEAS), a negative modulator of this receptor, might play a crucial role in modulating seizure frequency during the menstrual cycle. Following these studies it seems of interest to investigate possible variations, among other hormonal parameters, of THDOC and DHEAS in CE patients. The serum concentrations of progesterone (P4), pregnenolone, allopregnanolone (AP), THDOC, DHEAS, cortisol, and DHEAS/cortisol ratio were measured throughout the menstrual cycle at the 7th, 11th, 15th, 19th, 23rd, and 27th day from the onset of spontaneous menstrual blood loss in young premenopausal women with CE (n = 17) and age-matched controls (n = 13). At each time of the study, the serum concentration of THDOC and the DHEAS/cortisol ratio were lower (p < 0.05) in women with CE than in control women. The concentrations of P4, pregnenolone, and AP did not differ between the two groups of subjects. The reduced serum concentration of THDOC and the reduced DHEAS/cortisol ratio detected throughout the menstrual cycle in women with CE might play a role in CE. Moreover, the peculiar pattern of CE seizure exacerbation might suggest that these neuroendocrine variations are worth investigating in other epileptic syndromes, particularly in those characterized by relevant and uncontrolled variations in seizure frequency.


Psoralen-DNA photoreaction: controlled production of mono- and diadducts with nanosecond ultraviolet laser pulses.
Samples of DNA which contain adducts of a new psoralen derivative, but no cross-links, have been prepared by irradiating mixtures of DNA and the derivative with single, 15-nanosecond pulses of laser light. Succeeding pulses introduce cross-links. The ability to rapidly and selectively create monoadducts and corss-links may allow the use of psoralens as probes of dynamic processes in living cells.


Effects of CO2 enrichment and water stress on gas exchange of Liquidambar styraciflua and Pinus taeda seedlings grown under different irradiance levels.
The effects of CO2 enrichment and water stress on gas exchange of Liquidambar styraciflua L. (sweetgum) and Pinus taeda L. (loblolly pine) seedlings were examined for individuals grown from seed under high (1000 μmol·m-2·s-1) and low (250 μmol·m-2·s-1) photosynthetic photon flux density at 350, 675 and 1000 μl·l-1 CO2. At 8 weeks of age, half the seedlings in each CO2-irradiance treatment were subjected to a drying cycle which reduced plant water potential to about -2.5 MPa in the most stressed plants, while control plants remained well-watered (water potentials of -0.3 and -0.7 MPa for sweetgum and loblolly pine, respectively). During this stress cycle, whole seedling net photosynthesis, transpiration and stomatal conductance of plants from each CO2-irradiance-water treatment were measured under respective growth conditions.For both species, water stress effects on gas exchange were greatest under high irradiance conditions. Waterstressed plants had significantly lower photosynthesis rates than well-watered controls throughout most of the drying cycle, with the most severe inhibition occurring for low CO2, high irradiance-grown sweetgum seedlings. Carbon dioxide enrichment had little effect on gas exchange rates of either water-stressed or well-watered loblolly pine seedlings. In contrast, water stress effects were delayed for sweetgum seedlings grown at elevated CO2, particularly in the 1000 μl·l-1 CO2, high irradiance treatment where net photosynthesis, transpiration and conductance of stressed plants were 60, 36 and 33% of respective control values at the end of the drying cycle. Development of internal plant water deficits was slower for stressed sweetgum seedlings grown at elevated CO2. As a result, these seedlings maintained higher photosynthetic rates over the drying cycle than stressed sweetgum seedlings grown at 350 μl·l-1 CO2 and stressed loblolly pine seedlings grown at ambient and enriched CO2 levels. In addition, water-stressed sweetgum seedlings grown at elevated CO2 exhibited a substantial increase in water use efficiency.The results suggest that with the future increase in atmospheric CO2 concentration, sweetgum seedlings should "tolerate" longer exposure to low soil moisture, resulting in greater first year survival of seedlings on drier sites of abandoned fields in the North Carolina piedmont.


Anatomic variations of internal jugular vein, inferior petrosal sinus and its confluence pattern: Implications in inferior petrosal sinus catheterization.
The purpose of this study is to describe anatomic variations of the internal jugular vein (IJV), inferior petrosal sinus (IPS) and their confluence pattern and implications in IPS catheterization. The anatomic route of IPS after going out of the cranium and its confluence patterns with IJV and will supply knowledge about typing of IPS-IJV junction. A review of the literature was performed. There might be different routes for entering the intracranial segment of the IPS and multislice spiral computed tomography (MSCT) is effective in identifying the confluences of the IPS with the IJV and their courses. It is important to find the confluence of IPS with IJV for diagnosis and treatment of intracranial lesions via venous route. Meanwhile, IPS diameter at the confluence can significantly affect success of catheterization. The classification and the theory of the development of the caudal end of the IPS may be useful in establishing treatment strategies that involve endovascular manipulation via the IPS.


Solubilization and purification of alpha-mannosidase, a marker enzyme of vacuolar membranes in Saccharomyces cerevisiae.
Yeast alpha-mannosidase, a marker enzyme of vacuolar membranes, was solubilized and purified from commercial bakers' yeast. The alpha-mannosidase was solubilized efficiently with 10 mM Na2CO3. A high pH (greater than 8.5) and a sufficient amount of a detergent such as 0.2% (w/v) Triton X-100 were required to keep the enzyme in a soluble state. This suggested that the enzyme is either a peripheral membrane protein or an ecto-type integral membrane protein. After 4,300-fold purification by conventional chromatography, the alpha-mannosidase gave a single band on nondenaturing polyacrylamide gel electrophoresis, but could be fractionated into active isoforms, which consisted of 107-, 73-, and 31-kDa polypeptides, with a Mono Q anion exchange fast protein liquid chromatography system. Apparent molecular weight of the native enzyme was determined as 560,000. It suggested that the composition of isoforms will be described as (107 kDa)n (73 kDa)6-n (31 kDa)6-n, where n is 0-6. The 107- and 73-kDa polypeptides were purified further under denaturing conditions. One-dimensional peptide map analysis and immunological analysis of these polypeptides indicated that they are closely related proteins. Immunoblotting of crude cell lysates revealed that the 107-kDa polypeptide appeared first, and then the 73-kDa polypeptide appeared along growth phase. It suggested that proteolytic conversion of the 107-kDa polypeptide occurs to form the 73- and 31-kDa polypeptides and leads to formation of isoforms of the enzyme.


Alert on elongated in-hospital acute stroke management delays. An Aquitain cohort study.
The objectives were to analyze changes from 2012 to 2017 in different management times of stroke patients included in the Aquitaine stroke Observatory (ObA2). The studied times (onset-to-needle time-ONT, onset-to-door time-ODT, door-to-imaging time-DIT, door-to-needle time-DNT and imaging-to-needle time-INT) were described as median, interquartile ranges and proportion of patients within the recommended median time goals (ODT under 4hours, DIT within 20min; for thrombolyzed patients, DIT under 20min and a ONT under 4:30) to be compared with an objective of 50% of patients within said time goal. Globally, ODT was 160min, with 43.6% to 59.6% of patients within the ODT goal along the study period. With no improvement over time, the proportion of patients within the DIT goal stayed stable and at a low level (range: 5.5-7.0%) for all patients, decreasing from 25.2% to 11.4% for thrombolyzed patients. The proportion of thrombolyzed patients within the DNT goal varied from 15.1% to 30.3% during study period. These results highlight the urgent need for action to improve in-hospital management of stroke patients, focusing on delays between admission and imaging.


HST-1/FGF-4 gene activation induces spermatogenesis and prevents adriamycin-induced testicular toxicity.
We previously demonstrated expression of the HST-1/FGF-4 gene in the testis of normal adult animals, which suggests its possible role in spermatogenesis. For an understanding of its functional significance in the testis, conditional transgene expression was used. Precise genetic switches can be efficiently generated in a straightforward manner using adenovirus-carrying Cre recombinase, which means our new strategies promise to contribute substantially to a better and prompt understanding of the functions of genes in vivo by controlling the expression of any gene to any organ at any desired time. Our new method demonstrated for the first time that the specific gain of function of the HST-1/FGF-4 gene in the testis resulted in markedly enhanced spermatogenesis. To further investigate the function and therapeutic potency of HST-1/FGF-4, transgenic mice with enhanced HST-1/FGF-4 expression in the testis were exposed to adriamycin (ADR), an anticancer drug causing severe testicular toxicity. Degree of damage to spermatogenesis was assessed by sperm count, testicular weight, histology, and DNA ploidy. Induced expression of HST-1/FGF-4 markedly enhanced the recovery of ADR-induced testicular damage. Furthermore, adenoviruses carrying the HST-1/FGF-4 gene ameliorated testicular toxicity of ADR. These results with new adenovirus-mediated Cre/lox conditional mice indicated that HST-1/FGF-4 could be an important factor for spermatogenesis, presenting a new paradigm to treat impaired fertility.


Non-speculum sampling approaches for cervical screening in older women: randomised controlled trial.
Cervical cancer disproportionately affects women ≥65 years, especially those not screened regularly. Speculum use is a key barrier. To assess if offering non-speculum clinician-taken sampling and self-sampling increases uptake for lapsed attenders aged 50-64 years. Pragmatic randomised control trial conducted at 10 general practices in East London, UK. Participants were 784 women aged 50-64 years, last screened 6-15 years before randomisation. Intervention participants received a letter offering the choice of non-speculum clinician- or self-sampling. Control participants received usual care. The main outcome measure was uptake within 4 months. Screening uptake 4 months after randomisation was significantly higher in the intervention arm: 20.4% (n = 80/393) versus 4.9% in the control arm (n = 19/391, absolute difference 15.5%, 95% confidence interval [CI] = 11.0% to 20.0%, P<0.001). This was maintained at 12 months: intervention 30.5% (n = 120/393) versus control 13.6% (n = 53/391) (absolute difference 17.0%, 95% CI = 11.3% to 22.7%, P<0.001). Conventional screening attendance within 12 months was very similar for both intervention 12.7% (n = 50/393) and control 13.6% (n = 53/391) arms. Ethnic differences were seen in screening modality preference. More White women opted for self-sampling (50.7%, n = 38/75), whereas most Asian and Black women and those from other ethnic backgrounds opted for conventional screening. Offering non-speculum clinician-taken sampling and self-sampling substantially increases uptake in older lapsed attendee women. Non-speculum clinician sampling appeals to women who dislike the speculum but still prefer a clinician to take their sample. Providing a choice of screening modality may be important for optimising cervical screening uptake.


Impact of timing and dosing of four-factor prothrombin complex concentrate administration on outcomes in warfarin-associated intracranial hemorrhage.
The objective of this study was to evaluate clinical outcomes associated with time to administration and dose of four-factor prothrombin complex concentrate (4F-PCC) in patients with ICH on warfarin. This was a single-center retrospective analysis of patients with ICH on warfarin who received 4F-PCC. The site of the study was a large, Level I trauma, academic medical center with a dedicated neurologic intensive care unit and an emergency department (ED) that has approximately 72,000 visits annually. Patients were included if they were ≥18 years of age, diagnosed with ICH, had an INR >1 due to warfarin use, and received both 4F-PCC and IV vitamin K for anticoagulation reversal. Exclusion criteria included patients who were less than 18 years of age, were not currently taking warfarin, had a bleeding site other than ICH, were pregnant or incarcerated, had an inadequate medical record, had a left ventricular assist device, had known liver disease with Child-Pugh Class C, received anticoagulation with heparin therapy within 24 h of anticoagulation reversal, or did not receive vitamin K within 24 h of hospital admission. Our primary outcome was a composite of hematoma expansion or death due to neurologic injury. Treatment groups were defined as receipt of 4F-PCC within 0-30, 31-60, 61-90, 91-120 min, or greater than 120 min. Hematoma expansion was defined as any increase in hematoma size as assessed by a radiologist via standard 6-h CT. Death due to neurologic injury was defined as death prior to a repeat CT being performed or documentation of a neurologic cause of death. Adequate INR reversal (INR ≤1.3 on repeat INR) vs. inadequate INR reversal and weight-based vs. fixed-dose 4F-PCC were also assessed. A total of 94 patients met the inclusion criteria. Forty-one patients (43.6%) met the composite endpoint, including 60% of the 31-60 min group, 47.6% of the 61-90 min group, 71.4% of the 91-120 min group, and 30.6% of the >120-min group. A significant difference in primary outcome occurred between the 91-120 min and >120-min groups (71.4% vs. 30.6%; p= 0.005), but this difference was not observed when accounting for disparities in Glasgow Coma Scale (GCS). Patients with adequate INR reversal were less likely to meet the primary endpoint than those with inadequate INR reversal (28.1% vs. 58.6%; p= 0.0059). There was less failure of anticoagulation reversal with weight-based dosing compared with fixed dosing (24.2% vs. 65.0%; p< 0.001). No difference in clinical outcomes among 4F-PCC dosing strategies or time windows to administration was observed in patients with GCS <15. Rates of repeat INR ≤1.3 were higher with weight-based dosing, suggesting investigation of populations in which fixed dosing may be inappropriate is warranted.


An evaluation of quantitative agarose-gel electrophoresis of serum lipoproteins.
The method of Hatch et al. (Hatch, F.T., Lindgren, F.T., Adamson, G.L., Jensen, L.C. and Wong, A.W. (1973) J. Lab. Clin. Med. 81, 946-960) of quantitative determination of serum lipoproteins has been compared with preparative ultracentrifugation and chemical analysis of the lipoprotein fractions and a good concordance was demonstrated. The replacement of the coefficients proposed by Hatch et al. by the ones derived from the present study does not bring about relevant changes of the results when the harmonic mean of two calibration factors, derived from serum cholesterol and triglycerides, is used, thus indicating that this method of calculation minimizes the effect of variation of the chemical composition of lipoproteins. The method is sufficiently reliable and reproducible for practical pruposes and is recommended as the standard method for the clinical laboratory.


Editorial Commentary: Long Head Biceps Tendon Can Be Used Like a Split Skin Graft: Mesh It and Augment Rotator Cuff Repairs.
Full-thickness tears of the rotator cuff are common, and surgical treatment is indicated in most cases. Arthroscopic repair has become the standard technique, but despite improved surgical techniques, instrumentations, and implants, failure rates continue to be high and can reach 40% and more. Augmented repairs with allograft patches or autograft tissue, such as long head biceps tendon or fascia lata, have been used with mixed results. However, autograft augmentation seems to be resulting in superior outcomes and higher healing rates. Treating skin defects with split-skin grafts is the gold standard in burns and soft-tissue surgery. Given the limited supply of autograft, meshing autograft tendon and using it similar to a split-skin graft is a novel idea. When using a 2:1 expansion ratio, the long head biceps tendon can be formed into a porous scaffold with the in situ tenocytes, producing cytokines and promoting tenogenic differentiation. However, the scaffolds exhibited reduced tensile properties. The results are encouraging, and it will be interesting whether the clinical trials will demonstrate higher healing rates and better functional outcomes when compared to primary repair and allograft patch augmentation.


Seizure susceptibility and epileptogenesis are decreased in transgenic rats overexpressing neuropeptide Y.
Functional studies in epileptic tissue indicate that neuropeptide Y and some of its peptide analogs potently inhibit seizure activity. We investigated seizure susceptibility in transgenic rats overexpressing the rat neuropeptide Y gene under the control of its natural promoter. Seizures were induced in adult transgenic male rats and their wild-type littermates by i.c.v. injection of 0.3 microg kainic acid or by electrical kindling of the dorsal hippocampus. Transgenic rats showed a significant reduction in the number and duration of electroencephalographic seizures induced by kainate by 30% and 55% respectively (P<0.05 and 0.01). Transgenic rats were also less susceptible to epileptogenesis than wild-type littermates as demonstrated by a 65% increase in the number of electrical stimuli required to induce stage 5 seizures (P<0.01). This phenotype was associated with a strong and specific expression of neuropeptide Y mRNA in area CA1, a brain area involved in the seizure network. We conclude that endogenous neuropeptide Y overexpression in the rat hippocampus is associated with inhibition of seizures and epileptogenesis suggesting that this system may be a valuable target for developing novel antiepileptic treatments.


Norepinephrine neurons in mouse locus coeruleus express c-fos protein after N-methyl-D,L-aspartic acid (NMDA) treatment: relation to LH release.
In mouse, rat, and monkey, N-methyl-D,L-aspartic acid (NMDA) modulates gonadotropin releasing hormone (GnRH) release by an unknown mechanism. In previous studies we found that normal male mice consistently responded to NMDA administration with increased levels of plasma LH, as did most normal female mice and female hypogonadal mice with fetal preoptic area implants (HPG/POA). To investigate the mechanism of NMDA-induced GnRH release, immunocytochemistry of c-fos protein (FOS) was used for detection of neurons activated by NMDA administration. In both normal male and HPG/POA mice, FOS expression was unchanged in GnRH cells after NMDA administration. That neurosecretory cells can respond to NMDA was shown by the induction of FOS in many CRH (corticotropin-releasing hormone) cells in the paraventricular nucleus. Immunocytochemistry of beta-Endorphin, neuropeptide Y, tyrosine hydroxylase, an enzyme marker for catecholaminergic neurons, and glutamic acid decarboxylase, an enzyme marker for GABA neurons, was combined with that for FOS in normal male mice. Many noradrenergic (NA) neurons in the locus coeruleus (32-61%), and dopaminergic (DA) neurons in the mediobasal hypothalamus (15-31%) expressed FOS after NMDA administration while FOS was only rarely induced in neurons with the other neuromodulators tested. FOS was also induced in the locus coeruleus in male (43, 54%) and female (40, 55, 69%) HPG/POA mice. In contrast, few cells of the locus coeruleus expressed FOS in normal or HPG/POA mice after saline challenge. These results suggested that NMDA did not activate GnRH cells directly, but that NA neurons in the locus coeruleus were activated by NMDA and might be involved in stimulating GnRH release.(ABSTRACT TRUNCATED AT 250 WORDS)


Thermally Activated Delayed Fluorescence in Polymers: A New Route toward Highly Efficient Solution Processable OLEDs.
Efficient intermonomer thermally activated delayed fluorescence is demonstrated for the first time, opening a new route to achieving high-efficiency solution processable polymer light-emitting device materials. External quantum efficiency (EQE) of up to 10% is achieved in a simple fully solution-processed device structure, and routes for further EQE improvement identified.


Giant Extrinsic Spin Hall Effect in Platinum-Titanium Oxide Nanocomposite Films.
Although the spin Hall effect provides a pathway for efficient and fast current-induced manipulation of magnetization, application of spin-orbit torque magnetic random access memory with low power dissipation is still limited to spin Hall materials with low spin Hall angles or very high resistivities. This work reports a group of spin Hall materials, Pt1 -x (TiO2 )x nanocomposites, that combines a giant spin Hall effect with a low resistivity. The spin Hall angle of Pt1 -x (TiO2 )x in an yttrium iron garnet/Pt1 -x (TiO2 )x double-layer heterostructure is estimated from a combination of ferromagnetic resonance, spin pumping, and inverse spin Hall experiments. A giant spin Hall angle 1.607 ± 0.04 is obtained in a Pt0.94 (TiO2 )0.06 nanocomposite film, which is an increase by an order of magnitude compared with 0.051 ± 0.002 in pure Pt thin film under the same conditions. The great enhancement of spin Hall angle is attributed to strong side-jump induced by TiO2 impurities. These findings provide a new nanocomposite spin Hall material combining a giant spin Hall angle, low resistivity and excellent process compatibility with semiconductors for developing highly efficiency current-induced magnetization switching memory devices and logic devices.


[18F]FLT PET for diagnosis and staging of thoracic tumours.
The nucleoside analogue 3'-deoxy-3'-[18F]fluorothymidine (FLT) has been introduced for imaging of tumour cell proliferation by positron emission tomography (PET). This study evaluated the use of FLT in patients with thoracic tumours prior to treatment. Whole-body FLT PET was performed in 16 patients with 18 tumours [17 thoracic tumours (nine non-small cell lung cancers, five oesophageal carcinomas, two sarcomas, one Hodgkin's lymphoma) and one renal carcinoma] before treatment. Fluorine-18 fluorodeoxyglucose (FDG) PET was performed for comparison except in those patients with oesophageal carcinoma. For semi-quantitative analysis, the average and maximum standardised uptake values (avgSUV and maxSUV, respectively) (FLT, 114+/-20 min p.i.; FDG, 87+/-8 min p.i.; 50% isocontour region of interest) was calculated. All 17 thoracic tumours and 19/20 metastases revealed significant FLT accumulation, resulting in easy delineation from surrounding tissue. The additional small grade 1 renal carcinoma was not detected with either FLT or FDG. In most lung tumours (avgSUV 1.5-8.2) and metastases, FLT showed intense uptake. However, one of two spinal bone metastases was missed owing to the high physiological FLT uptake in the surrounding bone marrow. Oesophageal carcinoma primaries (avgSUV 2.7-10.0) and occasional metastases showed particularly favourable tumour/non-tumour contrast. Compared with FDG, tumour uptake of FLT was lower (avgSUV, P=0.0006; maxSUV, P=0.0001), with a significant linear correlation (avgSUV, r2=0.45; maxSUV, r2=0.49) between FLT and FDG. It is concluded that FLT PET accurately visualises thoracic tumour lesions. In the liver and the bone marrow, high physiological FLT uptake hampers detection of metastases. On the other hand, FLT may be favourable for imaging of brain metastases owing to the low physiological uptake.


Mobilization of the left and right fibrous trigones for relief of severe left ventricular outflow obstruction.
There is still no agreement about the optimal method of surgical relief of fixed subaortic stenosis, particularly the severe forms. The purpose of this study was to describe a new technique for the relief of subaortic stenosis based on analysis of the functional anatomy of the left ventricular outflow tract and pathophysiologic features of subaortic stenosis. We propose that one of the basic abnormalities in subaortic stenosis is interference with the hinge mechanism provided by the 2 fibrous trigones with progressive deposition of fibrous tissue in these angles. The technique described in this paper consists of excision of all components of the fibrous "ring," with mobilization of the left and right fibrous trigones. This results in the restoration of the normal dynamic behavior of the left ventricular outflow tract with maximal widening of the outflow tract as the result of backward displacement of the subaortic curtain and anterior leaflet of the mitral valve. This technique has been used in 57 consecutive patients who ranged in age between 5 months and 56 years (mean, 15.5 +/- 10.6 years). Gradients across the left ventricular outflow tract were between 45 and 200 mm Hg (mean, 86.7 mm Hg). Additional lesions were present in 10 patients, and 7 patients had had 8 previous operations on the left ventricular outflow tract. At operation, in addition to resection of subaortic stenosis, 3 patients had aortic valvotomy, 2 patients had homograft replacement of the aortic valve, 7 patients had patch closure of a ventricular septal defect, and 1 patient had open mitral valvotomy. There were 2 early deaths and 1 late sudden death during the follow-up period that ranged from 1 month to 25 years (mean, 15. 2 years). One patient experienced the development of endocarditis on the aortic valve 7 years after operation, which was successfully treated by homograft replacement. Postoperative gradients across the left ventricular outflow tract varied from no gradient to 30 mm Hg (mean, 8 mm Hg). There were no instances of recurrence of a gradient across the left ventricular outflow tract. It is concluded that mobilization of the left and right fibrous trigones results in durable relief of subaortic stenosis.


Neural correlates of symptom provocation in pediatric obsessive-compulsive disorder.
OBSESSIVE-COMPULSIVE DISORDER: (OCD)-affected adults and children exhibit three to four symptom dimensions with distinct but overlapping neural correlates. No symptom provocation behavioural or imaging study has examined all symptom dimensions in a pediatric OCD sample. METHOD: Clinically diagnosed pediatric OCD-affected participants (n = 25) as well as age, gender and Tanner pubertal stage-matched healthy controls (HCs; n = 24) (total sample: mean age = 14.77 ± 2.93 years; age range = 9-18 years; 35% male) viewed alternating blocks of OCD symptom provocation (Contamination, Bad Thoughts, and Just Right symptom dimensions), Fear, Neutral and Rest (i.e. fixation) conditions during functional magnetic resonance imaging. A region-of-interest analysis used seeds based upon results of an adult OCD meta-analysis RESULTS: OCD participants found OCD symptom-related stimuli bothersome, particularly when compared to controls in the "Just Right" symptom dimension. Pediatric OCD patients exhibited greater recruitment of the left superior temporal gyrus (STG) than healthy controls during combined symptom provocation versus neutral conditions. CONCLUSION: Findings suggest involvement of the temporal poles rather than in classic cortico-striatal-thalamico-cortical circuits in pediatric OCD during symptom provocation.


Perinatal risk factors for early childhood onset type 1 diabetes in Austria - a population-based study (1989-2005).
To investigate the rapid increase in incidence of type 1 diabetes mellitus (T1DM) in children <5 yr in Austria. Data of children born between 1989 and 2005 (n = 444) from the T1DM children incidence registry were linked with birth certificates (n = 1 407 829). Age of mother, level of education, birth weight, birth length, body mass index, and APGAR score at 10 min were not significant. Boys have about 25% higher risk than girls [hazard ratio = 0.75, 95% confidence interval (CI): 0.62-0.91]. The risk of developing diabetes increases over time significantly (1989-1991 vs. 2001-2005, hazard ratio = 2.86, 95% CI: 2.07-3.94). The linear effect of parity is borderline significant (p = 0.045), with lower risks for second and later born siblings. Marital status is significant [hazard ratio = 0.73, 95% CI: 0.57-0.90)]. Native-born children exhibit twice as high risk as non-native children (hazard ratio = 0.51, 95% CI: 0.37-0.71). Birth weight shows a positive but not significant effect on risk of T1DM. In this very young and rapidly increasing cohort of diabetic children <5 yr of age, no association with birth weight but with year of birth, gestational age, nationality and parity could be observed.


Educational efficacy of computer-assisted instruction with interactive videodisc in radiology.
To create a robust, functional computer-assisted instruction (CAI)-videodisc program and to demonstrate its educational efficacy. After creating a CAI-videodisc program in skeletal radiology for a two-screen Macintosh system, 36 medical students and 162 radiology residents entered a controlled study with paired pre- and posttests. Subjects also compared CAI-videodisc with other educational media. Medical students using the CAI-videodisc improved their mean pre- and posttests. Subjects also compared CAI-videodisc with other educational media. Medical students using the CAI-videodisc improved their mean pre- and posttest scores from 50.9 to 70.9 (P < .001, control group scores 50.1 and 50.6) and residents (using a different test) improved from 45.4 to 70.9 (P < .001, control group scores 49.6 and 46.1). Medical students and residents favored CAI-videodisc over teaching files, textbooks, videotapes, and slide-audiotapes. A functional CAI-videodisc program was created and demonstrated to be educationally effective.


Interaction between a NMDA receptor antagonist, AP-5 and an AMPA receptor antagonist, YM 872 in antinociception in the spinal cord.
The intrathecal N-methyl-D-aspartate (NMDA) receptor antagonist, AP-5 and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, YM 872 showed inhibition on both acute and facilitated nociception in our previous study. The present study was performed to investigate the interaction between intrathecal AP-5 and YM 872 in antinociception for acute and chronic nociception. Sprague-Dawley rats with lumbar intrathecal catheters were tested for their thermal tail withdrawal response and for their paw flinches by formalin injection after intrathecal administration of AP-5 or YM 872. The effects of the combination were tested by an isobolographic analysis using 50% effective dose (ED50). Total fractional dose was calculated as (ED50 dose of AP-5 in combination)/(ED50 dose of AP-5 alone)+(ED50 dose of YM 872 in combination)/(ED50 dose of YM 872 alone). Intrathecally administered AP-5, YM 872, and their combination produced dose-dependent increases of the tail-flick latency and decreases in the number of flinches in both phase 1 and 2 of the formalin test. The ED50 values of the combination were significantly lower than the calculated additive values (P<0.01). Total fractional dose value was 0.22 in the tail flick test, 0.12 in the phase 1 and 0.14 in the phase 2 of the formalin test. An NMDA receptor antagonist, AP-5 and an AMPA receptor antagonist, YM 872 had synergistic antinociceptive effects on both acute thermal and inflammatory induced acute and facilitated nociception.


Giant basal cell carcinoma with metastasis and secondary amyloidosis: report of case.
Basal cell carcinoma of the skin is a slow growing relatively benign tumor usually located on the head and neck. Although rare, metastasis to lymph nodes or parenchymatous organs has been reported previously (1-9). We wish to add another case of metastasizing basal cell carcinoma of the skin, which presented certain unique features only rarely reported (1), namely complicating amyloidosis in the kidneys, the lymph nodes, the spleen and probably in the intestinal canal.


Kinetics of association of human proteinases with human alpha 2-macroglobulin.
Association rates have been determined for the interaction of human alpha 2-macroglobulin with human neutrophil elastase, cathepsin G, and human plasma kallikrein. Both of the neutrophil enzymes are rapidly inactivated by this inhibitor; however, the inactivation of plasma kallikrein is much slower. Comparison of the rates of inactivation with those already established for other inhibitors clearly indicate that alpha 1-proteinase inhibitor is the controlling inhibitor for neutrophil elastase and alpha 1-antichymotrypsin for cathepsin G, alpha 2-macroglobulin acting only as a secondary inhibitor. The control of plasma kallikrein would appear to be rather poor since neither alpha 2-macroglobulin nor C1-inhibitor appears to react very rapidly with this proteinase. Thus, a primary role for alpha 2-macroglobulin in directly inactivating proteinases in blood, under normal physiological conditions, remains to be established.


Tuning quantum measurements to control chaos.
Environment-induced decoherence has long been recognised as being of crucial importance in the study of chaos in quantum systems. In particular, the exact form and strength of the system-environment interaction play a major role in the quantum-to-classical transition of chaotic systems. In this work we focus on the effect of varying monitoring strategies, i.e. for a given decoherence model and a fixed environmental coupling, there is still freedom on how to monitor a quantum system. We show here that there is a region between the deep quantum regime and the classical limit where the choice of the monitoring parameter allows one to control the complex behaviour of the system, leading to either the emergence or suppression of chaos. Our work shows that this is a result from the interplay between quantum interference effects induced by the nonlinear dynamics and the effectiveness of the decoherence for different measurement schemes.


Uptake of PAHs into polyoxymethylene and application to oil-soot (lampblack)-impacted soil samples.
Polyoxymethylene (POM) is a polymeric material used increasingly in passive sampling of hydrophobic organic contaminants such as PAHs and PCBs in soils and sediments. In this study, we examined the sorption behavior of 12 PAH compounds to POM and observed linear isotherms spanning two orders of magnitude of aqueous concentrations. Uptake kinetic studies performed in batch systems for up to 54 d with two different volume ratios of POM-to-aqueous phase were evaluated with coupled diffusion and mass transfer models to simulate the movement of PAHs during the uptake process and to assess the physicochemical properties and experimental conditions that control uptake rates. Diffusion coefficients of PAHs in POM were estimated to be well correlated with diffusants' molecular weights as D(POM) proportional, variant(MW)(-3), descending from 2.3 x 10(-10) cm(2) s(-1) for naphthalene to 7.0 x 10(-11) cm(2) s(-1) for pyrene. The uptake rates for PAHs with log K(ow)<5.8 were controlled by the POM phase and the hydrophobicity of PAH compounds. For more hydrophobic PAH compounds, the aqueous boundary layer played an increasingly important role in determining the overall mass transfer rate. The POM partitioning technique was demonstrated to agree well with two other procedures for measuring PAH soil-water distribution coefficients in oil-soot (lampblack) containing soil samples.


Silencing RNAs expressed from W-linked PxyMasc "retrocopies" target that gene during female sex determination in Plutella xylostella.
The Lepidoptera are an insect order of cultural, economic, and environmental importance, representing ∼10% of all described living species. Yet, for all but one of these species (silkmoth, Bombyx mori), the molecular genetics of how sexual fate is determined remains unknown. We investigated this in the diamondback moth (Plutella xylostella), a globally important, highly invasive, and economically damaging pest of cruciferous crops. Our previous work uncovered a regulator of male sex determination in P. xylostella-PxyMasc, a homolog of B. mori Masculinizer-which, although initially expressed in embryos of both sexes, is then reduced in female embryos, leading to female-specific splicing of doublesex. Here, through sequencing small RNA libraries generated from early embryos and sexed larval pools, we identified a variety of small silencing RNAs (predominantly Piwi-interacting RNAs [piRNAs]) complementary to PxyMasc, whose temporal expression correlated with the reduction in PxyMasc transcript observed previously in females. Analysis of these small RNAs showed that they are expressed from tandemly arranged, multicopy arrays found exclusively on the W (female-specific) chromosome, which we term "Pxyfem". Analysis of the Pxyfem sequences showed that they are partial complementary DNAs (cDNAs) of PxyMasc messenger RNA (mRNA) transcripts, likely integrated into transposable element graveyards by the noncanonical action of retrotransposons (retrocopies), and that their apparent similarity to B. mori feminizer more probably represents convergent evolution. Our study helps elucidate the sex determination cascade in this globally important pest and highlights the "shortcuts" that retrotransposition events can facilitate in the evolution of complex molecular cascades, including sex determination.


Effects of ultrasound-guided erector spinae plane block on postoperative acute pain and chronic post-surgical pain in patients underwent video-assisted thoracoscopic lobectomy: a prospective randomized, controlled trial.
To investigate the effects of ultrasound-guided erector spinae plane block (ESPB) on acute and chronic post-surgical pain in patients underwent video-assisted thoracoscopic lobectomy. A total of 94 patients, who underwent elective unilateral video-assisted thoracoscopic lobotomy from August 2021 to December 2021 were randomly divided into general anesthesia group (group A, n = 46) and ESPB combined with general anesthesia group (group B, n = 48) by computer. Patient controlled intravenous analgesia(PCIA) was performed in both groups after operation. The numerical rating scale(NRS) of rest and cough pain at post anesthesia care unit(PACU), 2 h, 6 h, 12 h, 24 and 48 h after operation, frequency of PCIA in 24 h after operation, frequency of rescue analgesia, patient satisfaction, adverse reactions and complications were recorded in the two groups. Incidence of chronic pain at 3 months and 6 months after operation, the effect of daily life and rating of chronic pain management measures were recorded in the two groups. Compared with group A, rest and cough NRS score at 2 h, 6 h, 12 h, 24 and 48 h after surgery, frequency of PCIA use at 24 h after surgery, frequency of rescue analgesia were significantly decreased in group B (P < 0.05). There was no significant difference in NRS scores of rest and cough at PACU after operation between 2 groups after surgery at post anesthesia care unit (P > 0.05). There were no significant differences in the incidence of postoperative chronic pain between the 2 groups(P > 0.05);The effect of postoperative chronic pain on daily life and pain management measures in group B were significantly lower than those in group A(P < 0.05). Compared with group A, patients in group B had higher satisfaction degree, lower incidence of postoperative nausea and vomiting(PONV), and lower incidence of agitation during anesthesia recovery (P < 0.05). There were no pneumothorax, hematoma and toxicity of local anesthetic in the 2 groups. Ultrasound-guided erector spinae plane block can significantly reduce acute post-surgical pain, can not reduce the incidence of chronic post-surgical pain, but can significantly reduce the severity of chronic pain in patients underwent video-assisted thoracoscopic lobectomy. ChiCTR2100050313,date of registration:26/08/2021.


[Experimental study of the effect of TNP-470 on human salivary adenoid cystic carcinoma cell in vitro].
To investigate the effects of TNP-470 on human salivary adenoid cystic carcinoma cell line ACC M in vitro. Cell proliferation was assessed by MTT assays and dye exclusion counting. Morphological changes of apoptosis were observed with fluorescent microscope. DNA ladder, apoptosis rate and cell cycle were examined by DNA agarose gel electronphores and fluorescence flow cytometry (FCM), respectively. The 50% inhibitory concentrations (IC50) of TNP-470 on ACC-M cells proliferation by MTT assays and dye exclusion counting were 40.68microg/ml and 46.38microg/ml. Apoptosis were observed by fluorescent microscope. DNA electrophoresis for the cells treated with TNP-470 showed brighter DNA ladder; Sub-G1 peak and G2/M arrest were also determined by FCM (P<0.01). TNP-470 has the effect of inducing apoptosis in ACC-M cells in vitro, which may be one of its antitumor mechanisms.


Renal physiology of nocturia.
Renal function, diurnal fluctuations in arginine vasopressin (AVP) secretion, sex, and advanced age affect urine formation and may contribute to nocturia. Renal effects of AVP are mediated by AVP V2 receptors in the kidney collecting duct. Changes in AVP concentration have the greatest relative effects on urine volume when AVP levels are low; therefore small changes can have a large effect on renal water excretion. AVP is the major regulator of water excretion by the kidneys, and AVP levels have been shown to affect nocturnal voiding. Results of several studies show that patients with nocturia had no significant variation in plasma AVP, whereas patients without nocturia had significant diurnal variation in plasma AVP. The V2 receptor gene is located on the X chromosome, which has important sex-specific consequences. For example, mutations in the V2 gene can cause nephrogenic diabetes insipidus, predominantly in men. Age-related changes in water metabolism are associated with overall body composition, kidney, and brain. Older people generally experience decreased extracellular fluid and plasma volume, which leads to increased adverse consequences from net body water gain or loss. Renal function declines with age, and the ability to concentrate urine and conserve sodium is reduced in the elderly. Thirst perception is also decreased in the elderly, who, compared with younger people, tend to hypersecrete AVP in response to higher plasma osmolality, possibly resulting in hyponatremia. These aspects of renal physiology should be considered when antidiuretic drugs are prescribed for the treatment of nocturia.


Quantum spinning photonic circulator.
We propose a scheme to realize a four-port quantum optical circulator for critical coupling of a spinning Kerr resonator to two tapered fibers. Its nonreciprocal effect arises from the Fizeau drag induced splitting of the resonance frequencies of the two counter-travelling optical modes. The transmitted photons exhibit direction dependent quantum correlations and nonreciprocal photon blockade occurs for photons transferred between the two fibers. Moreover, the quantum optical circulator is robust against the back scattering induced by intermodal coupling between counter-travelling optical modes. The present quantum optical circulator has significant potential as an elementary cell in chiral quantum information processing without magnetic field.


Coming home upset: Gender, marital satisfaction, and the daily spillover of workday experience into couple interactions.
This study explored how daily changes in workday pace and end-of-the-workday mood were related to nightly variations in withdrawn and angry marital behavior. For 3 days, 82 husbands and wives from 42 couples completed questionnaires at the end of the workday and at bedtime. More negatively arousing workdays were linked with angrier marital behavior for women and less angry and more withdrawn behavior for men. Daily changes in workday pace predicted fluctuations in women's, but not men's, marital behavior. Several of these workday-marital behavior connections varied by level of marital satisfaction. In contrast to the gender differences in responses to workday stress, no differences were found in typical marital behaviors. These findings suggest that gender differences are enhanced under stress.


Competitive ion-exchange adsorption of proteins: competitive isotherms with controlled competitor concentration.
The competitive adsorption processes inevitably present in chromatographic separations of complex mixtures have not been extensively studied. This is partly due to the difficulty of measuring true competitive isotherms, in which all system parameters (including competitor concentrations) are held constant. We report a novel approach to determining competitive protein adsorption isotherms in which the competitor concentration is held constant across the entire isotherm. By using the heme prosthetic group in cytochrome b5 as a quantitative spectrophotometric label, competitive isotherms between cytochrome b5 and alpha-lactalbumin can be constructed. Similarly, manganese-substituted protoporphyrin IX heme replacement allows the non-perturbing labeling of individual cytochrome b5 conservative surface charge mutants by replacement of a single atom in the interior of the protein. This labeling allows the study of competition between cytochrome b5 charge mutants of identical size and shape, which differ only in charge arrangement. Using these techniques, the effect of competing species on equilibrium behavior and the apparent heterogeneity of anion-exchange adsorbents in the presence of competitors can be quantitatively studied by fitting the data to two popular single-component binding models, the Temkin and the Langmuir-Freundlich (L-F) isotherms.


[Endovascular Treatment for Vascular Injuries of the Extremities].
Vascular injuries of the extremities are associated with a high mortality rate. Conventionally, open surgery is the treatment of choice for peripheral vascular injuries. However, rapid development of devices and techniques in recent years has significantly increased the utilization and clinical application of endovascular treatment. Endovascular options for peripheral vascular injuries include stent-graft placement and embolization. The surgical approach is difficult in cases of axillo-subclavian or iliac artery injuries, and stent-graft placement is a widely accepted alternative to open surgery. Embolization can be considered for arterial injuries associated with active bleeding, pseudoaneurysms, and arteriovenous fistula and in patients in whom embolization can be safely performed without a risk of ischemic complications in the extremities. Endovascular treatment is a minimally invasive procedure and is useful as a simultaneous diagnostic and therapeutic approach, which serve as advantages of this technique that is widely utilized for vascular injuries of the extremities.


Acute fibrinoid organizing pneumonia after lung transplantation.
The barrier to long-term success after lung transplantation is the development of chronic lung allograft dysfunction. As the experience with lung transplantation accrues, it has become increasingly apparent that not all chronic allograft dysfunction is consistent with the traditionally recognized small-airway histological process of obliterative bronchiolitis (OB). To identify and describe chronic allograft dysfunction that is not consistent with the well-described bronchiolitis obliterans syndrome and to further characterize a novel histopathological process, acute fibrinoid organizing pneumonia (AFOP), that has led invariably to respiratory decline and death after lung transplantation. We evaluated 194 bilateral lung transplant recipients, identifying 87 individuals who developed chronic allograft dysfunction. They were then classified according to features on spirometry, chest imaging, and histopathological specimens. Two main phenotypes of chronic allograft dysfunction were identified; 39 (45%) recipients were categorized as having developed OB and 22 (25%) as having AFOP. Survival in those who developed AFOP was significantly worse than in those who developed OB (median time to death 101 vs. 294 d; P = 0.02), with all exhibiting a rapid decline in respiratory function leading to death. AFOP is a novel form of chronic allograft dysfunction exhibiting spirometric, radiological, and histopathological characteristics that differentiate it from OB. The further characterization of chronic allograft dysfunction and its heterogeneous manifestations will allow the targeting of clinical and experimental efforts to prevent and treat chronic allograft dysfunction.


An improved screening system for the early detection of congenital dislocation of the hip.
A screening programme for congenital dislocation of the hip in which physiotherapists examine all neonates is described, together with the results over a 7-year period. All easily reducible dislocated and dislocatable hips are splinted within 2-5 days of birth. Subluxable or "slidey" hips are identified and followed up but not splinted. Risk groups are also identified and followed up. There was a progressive decrease in the number of late diagnosed cases, a result suggesting that even late-presenting acetabular dysplasia can be eliminated by neonatal screening.


Natural history of untreated renal cell carcinoma with venous tumor thrombus.
The natural history of untreated renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is poorly characterized. We aimed to describe the natural history of this disease, and to identify prognostic factors associated with disease-specific survival. We identified patients in the Surveillance, Epidemiology, and End Results (SEER) database with untreated renal cell carcinoma and venous tumor thrombi. Disease-specific median and 1-year survival rates were determined, and disease-free survival curves were plotted using the Kaplan-Meier method. Multivariable Cox regression analyses were performed to identify factors associated with disease-specific and overall survival in this patient group. Of 2,265 patients with RCC and VTT, 390 (17%) underwent no treatment; 278 (71%) patients died during follow-up; of these, 243 deaths (87%) were due to RCC. Median and 1-year disease-specific survival for this group was 5 months and 29%, respectively. On multivariable analysis, the extent of tumor thrombus (HR 1.7 for T3c vs. T3b, 95% CI 1.0-2.7) and the presence of metastases (HR 3.1 for M+ vs. M0, 95% CI 1.7-5.5) were most strongly associated with disease-specific mortality. Prognosis is poor for the majority of untreated patients with RCC and VTT. Supradiaphragmatic thrombi and distant metastases are adverse prognostic factors in this patient group. This information is important when counseling patients as to the risk and benefits of surgical vs. nonoperative management of RCC and VTT.


The effect of exogenous GM1 ganglioside on kindled-amygdaloid seizures.
The effects of 12 daily doses of 30 mg/kg GM1 ganglioside i.p. on the acquisition of kindled-amygdaloid seizures in the rat was studied. No modification in the rate of kindling or the expression of the elicited seizures was noted during the acquisition phase. Further studies with additional fully amygdaloid kindled rats failed to show significant modification of suprathreshold or threshold elicited seizures after single 30-60 mg/kg i.p. doses of GM1 ganglioside. Despite previous studies which have shown antibodies to GM1 ganglioside to be convulsive, no anticonvulsant activity was demonstrated in this study with exogenous GM1 ganglioside using a battery of kindled-amygdaloid seizure tests in the rat.


Perceived Stress Scale (PSS-10) psychometric properties in migrants and native Germans.
With the increasing diversity of the German population, it is important to test the psychometric validity and reliability of the German version Perceived Stress Scale (PSS-10) specifically between German natives and residents with a migration background. Using nationally representative data (N = 2527), this study conducted an Exploratory Factor Analysis (EFA) to determine the most appropriate factor structure, a Multi-Group Confirmatory Factor Analysis (MGCFA) to compare the validity of the two-factor structure and tested the PSS-10 measurement invariance between the German native and migrant sub-samples. Lastly, reliability of the PSS-10 was examined via Cronbach's alpha, omega and individual item analyses across the two sub-samples. The EFA results support a two-factor structure in the migrant sample. The MGCFA showed adequate model fit for both sub-samples and the PSS-10 is strict invariant between German natives and migrants. Cronbach's alpha and omega for Perceived Helplessness (PHS: factor 1) and Perceived Self-Efficacy (PSES: factor 2) demonstrate good internal consistency in both German and migrant sub-samples. The key conclusions are: (1) the German version PSS-10 is suitable for German residents with a migration background. (2) Despite good internal consistency for the total scale, the PSS-10 measures two aspects: (a) perceived helplessness and (b) perceived self-efficacy. Future research would profit from analyzing the two subscales separately, not only using the total score.


Caregiver survey of pharmacotherapy to treat attention deficit/hyperactivity disorder in individuals with Williams syndrome.
Williams syndrome (WS) is a genetic condition characterized by a unique neurocognitive and behavioral profile, including increased incidence of attention deficit/hyperactivity disorder (ADHD). The purpose of the present study was to examine the perceived helpfulness and side effects of medications used to treat ADHD (methylphenidate class, amphetamine class, atomoxetine) in individuals with WS. This was accomplished with a survey of parents/caregivers of individuals with WS through the Williams Syndrome Association. Five-hundred twelve (512) parents/caregivers responded to the survey regarding their child's/adult child's use of ADHD medications. Twenty-seven percent (27%) of the individuals had been prescribed a medication for ADHD, most commonly a methylphenidate class medication. OROS-methylphenidate was reported as the most helpful methylphenidate class formulation, with 74% reporting it at least somewhat helpful. Survey participants reported similar side effects as typically developing controls, but to a greater degree. Irritability was the most commonly endorsed side effect of an ADHD medication (38%). Individuals reported use of stimulant medications in the presence and absence of underlying cardiac conditions, with 56% of ADHD medication users reporting supravalvular aortic stenosis, 36% pulmonary artery stenosis, and 25% systemic hypertension. Individuals taking ADHD medications were more likely to report dental problems (p=0.004). Additional studies are needed to further investigate these findings and examine short-versus long-acting stimulant medications and dosage effects.


Surgical resection of retrorectal tumours in adults: long-term results in 47 patients.
Retrorectal tumours (RT) are uncommon, and diagnosis and management remain difficult. The aim of this study was to evaluate the results of the surgical management of RT in our institution. Medical notes of all patients operated on for RT were reviewed. Clinical, radiological, surgical, histological data as well as morbidity and long-term results were noted. Forty-seven patients [34 women (72%), mean age 45.8 (range 17-85) years] underwent surgery for RT between 1997 and 2011. The commonest symptoms were pain (n = 31) and suppuration (n = 10). Thirty-nine (83%) patients underwent preoperative magnetic resonance imaging (MRI). Malignant lesions exhibited typical characteristics on MRI including heterogeneity (n = 5, 83%), solid appearance (n = 4, 67%), a low-T1 signal and high-T2 intensity (n = 5, 83%), enhancement after gadolinium injection (n = 5, 83%), irregular margin (n = 4, 67%) and extension above S3 (i = 5, 83%). A Kraske approach was used in 42 (89%) patients with resection of the coccyx in 25 (60%) and an abdominal or combined approach for the remaining five. Four patients developed complications (two haematoma, two abscess), but only one (haematoma) required reoperation. Histological examination showed 38 (80.9%) benign lesions. After a median follow-up of 71 (2-168) months, 5-year disease-free survival was 75% for malignant lesions and 93.1% for benign lesions (P = 0.023). Four (4/42; 9.5%) patients had moderate perineal pain after a Kraske approach, while no anal dysfunction was seen. Magnetic resonance imaging was the most helpful investigation for retrorectal tumours. The posterior trans-sacrococcygeal approach is the procedure of choice for complete resection for most, especially for benign and cystic lesions without extension above S2.


Management of severe malaria.
Prompt diagnosis and early institution of therapy is an important determinant of outcome in severe falciparum malaria. Thick smears are the gold standard for diagnosis; in situations where reliable microscopy is not available, tests based on HRP-2 antigen/parasite LDH are useful. As there is widespread resistance to chloroquine in P falciparum in India, the choice for specific antimalarial therapy is between quinine and artermisinin derivatives. Randomized controlled trials have not revealed any significant benefit of the artemisinin derivatives over quinine in quinine sensitive areas. Also, if quinine is administered in the recommended way, the side effects are no greater than artemisinins. However, as the artemisinin derivatives are easier to administer, their use in severe malaria in India is increasing. It is vital that we use these drugs in a rational and judicious manner to prevent development of drug resistance. Supportive care, early diagnosis and management of complications are as essential as antimalarial therapy. The role of exchange blood transfusion in the management of severe malaria is still controversial. It may be considered in the presence of high parasites counts (>10%) with multiorgan dysfunction if adequate quantities of safe blood are available.


Folic acid-mediated fibrosis is driven by C5a receptor 1-mediated activation of kidney myeloid cells.
We have previously reported that increased expression and activation of kidney cell complement components play an important role in the pathogenesis of renal scarring. Here, we used floxed green fluorescent protein (GFP)-C5a receptor 1 (C5aR1) knockin mice (GFP-C5ar1fl/fl) and the model of folic acid (FA)-induced kidney injury to define the cell types and potential mechanisms by which increased C5aR1 activation leads to fibrosis. Using flow cytometry and confocal microscopy, we identified macrophages as the major interstitial cell type showing increased expression of C5aR1 in FA-treated mice. C5ar1fl/fl.Lyz2Cre+/- mice, in which C5aR1 has been specifically deleted in lysozyme M-expressing myeloid cells, experienced reduced fibrosis compared with control C5ar1fl/fl mice. Examination of C5aR1-expressing macrophage transcriptomes by gene set enrichment analysis demonstrated that these cells were enriched in pathways corresponding to the complement cascade, collagen formation, and the NABA matrisome, strongly pointing to their critical roles in tissue repair/scarring. Since C5aR1 was also detected in a small population of platelet-derived growth factor receptor-β+ GFP+ cells, we developed C5ar1fl/fl.Foxd1Cre+/- mice, in which C5aR1 is deleted specifically in pericytes, and found reduced FA-induced fibrosis. Primary cell cultures of platelet-derived growth factor receptor-β+ pericytes isolated from FA-treated C5ar1fl/fl.Foxd1Cre+/- mice showed reduced secretion of several cytokines, including IL-6 and macrophage inflammatory protein-2, compared with pericytes isolated from FA-treated control GFP-C5ar1fl/fl mice. Collectively, these data imply that C5a/C5aR1 axis activation primarily in interstitial cells contributes to the development of renal fibrosis.NEW & NOTEWORTHY This study used novel green fluorescent protein C5a receptor 1 floxed mice and the model of folic acid-mediated kidney fibrosis to demonstrate the pathogenic role of increased expression of this complement receptor on macrophages.


Responses of growth, malformation, and thyroid hormone-dependent genes expression in Bufo gargarizans embryos following chronic exposure to Pb2.
The aim of this study was to examine the adverse effects of lead (Pb) exposure on Bufo gargarizans embryos. The 96 h-LC50 of Pb2+ for B. gargarizans embryos was determined to be 26.6 mg L-1 after an acute test. In the chronic test, B. gargarizans embryos at Gosner stage 3 were exposed to 10~2000 μg Pb2+ L-1 during embryogenesis. Total length, weight, developmental stage, and malformation were monitored. In addition, the transcript levels of type II and type III iodothyronine deiodinase (Dio2 and Dio3) and thyroid hormone receptors (TRα and TRβ) were determined to assess the thyroid-disrupting effects of Pb2+. Slightly increased growth and development of B. gargarizans embryos were observed at low concentrations of Pb2+ (10, 50, and 100 μg L-1), while retarded growth and development were found at high concentrations of Pb2+ (1000 and 2000 μg L-1). In addition, Pb2+ exposure induced morphological abnormalities, which were characterized by edema at tail, wavy fin, abdominal edema, stunted growth, hyperplasia, and axial flexures in B. gargarizans embryos. Furthermore, our results showed that exposure to 2000 μg Pb2+ L-1 decreased the transcript levels of Dio2, TRα, and TRβ, but it increased Dio3 mRNA level. In contrast, exposure to 50 μg Pb2+ L-1 increased TRα mRNA level and decreased Dio3 mRNA level. These results suggested that Pb2+ might have thyroid-disrupting effects, leading to the disruption of growth and development in B. gargarizans embryos.


mRNA 5' ends targeted by cytoplasmic recapping cluster at CAGE tags and select transcripts are alternatively spliced.
Until cytoplasmic recapping was discovered, decapping was thought to irreversibly destine an mRNA to degradation. Contradicting this idea, we readily observe mRNAs targeted by cytoplasmic capping in uncapped, yet stable forms. 5' rapid amplification of cDNA ends (RACE) shows that nearly all uncapped ends correspond to capped analysis of gene expression tags and that the recapping of ZNF207 mRNA may be restricted to a single splice isoform. Here, a modified RACE approach detected uncapped 5' RNA ends mapping to 46 mRNAs in cells expressing a dominant negative cytoplasmic capping enzyme and in normal cells. Eleven of 46 cloned mRNAs also contained splice isoform-limiting sequences. Collectively, these data reinforce earlier work and suggest that alternative splicing may play a role in targeting transcripts for - and/or determining the position of - cytoplasmic capping.


Influence of a dietary n-3 fatty acid deficiency on the cerebral catecholamine contents, EEG and learning ability in rat.
Female rats were fed on a diet deficient in (n-3) fatty acid or enriched in docosahexaenoic acid (DHA) diet from mating and throughout pregnancy and lactation. Pups fed on the same diet as their dams were used for experiments. The effects of dietary (n-3) fatty acid deficiency on cerebral catecholamine contents and electroencephalogram (EEG) in rat pups during the postnatal development were investigated. The (n-3) deficient rat pups showed significantly lower levels of noradrenaline (NA) in cerebral cortex, hippocampus and striatum, compared with those in the DHA adequate rats. Dopamine (DA) contents were significantly lower in the (n-3) deficient rats until the 7th day of age. These results were consistent with observations in the EEG analysis, relative powers of fast activities in the EEG recorded from the (n-3) deficient rats were significantly lower than those in the DHA adequate rats. The effect of supplementation with DHA in (n-3) deficient rats on learning ability was also studied in a model of learning, active avoidance test and three-panel run way test, after weaning. Although the percentages of avoidance in the (n-3) deficient rats (saline group) were constantly 20% or less until the 3rd session, the percentage of avoidance in the DHA supplemented rats rapidly increased to 53% following the first administration. While in the three-panel runway test, there were no significant differences between two groups. These results suggest that chronic consumption of a (n-3) fatty acid deficient diet could modify the biosynthesis of catecholamine in the brain, and might induce the behavioral disturbances. Furthermore, the decreased learning ability induced by (n-3) deficiency in the active avoidance test is a reversible following a supplementing DHA after the weaning.


Isolation and characterization of hexokinase genes PsHXK1 and PsHXK2 from tree peony (Paeonia suffruticosa Andrews).
Hexokinase (HXK) plays important roles in hexose phosphorylation and sugar signaling. HXK regulates the glucose-induced accumulation of anthocyanin in many species. Little is known about the biological function of the HXK gene family in Paeonia suffruticosa. cDNA sequences of two hexokinase genes PsHXK1 and PsHXK2 were isolated using RACE-PCR and RT-PCR from P. suffruticosa. PsHXK1 encodes 498 amino acids with a 1497-bp open reading frame (ORF), and PsHXK2 contains 493 amino acids with a 1482-bp ORF. Sequence and phylogenetic analyses suggest that PsHXK1 and PsHXK2 belong to type-B HXK and may function as glucose sensors. PsHXK1 and PsHXK2 mRNA were detected in all tested tissues. PsHXK1 is highly expressed in petals and stamens, while PsHXK2 is highly expressed in stamens. At the former stages of flower opening, PsHXK1 and PsHXK2 show higher expression levels in on-tree flowers compared with cut flowers. Overexpressing PsHXK1 and PsHXK2 in Arabidopsis enhances glucose sensitivity, inhibits plant growth in response to glucose, and induces anthocyanin accumulation in response to the high level of glucose. Overall, our results primarily reveal the biological function of PsHXK1 and PsHXK2, especially their involvement in glucose-induced anthocyanin accumulation.


Appendiceal neuroendocrine neoplasms and resection of the mesoappendix: a retrospective comparative study.
Incidental appendiceal neoplasms are identified in approximately 1% of the specimens of suspected appendicitis. The current institutional policy is to perform en bloc mesoappendix resection during routine laparoscopic appendicectomy allowing for staging, reducing the need for oncological right hemicolectomy (ORH). Herein, we review en bloc mesoappendicectomy in clinical practice and its effects on the rate of ORH. We reviewed all cases of appendicectomy performed at the Auckland City Hospital between 1 May 2014 and 31 May 2019. Clinical notes and histopathological reports were reviewed. All neoplasms, surgical techniques and the need for further surgery were analysed. A total of 2455 appendicectomies were performed with an approximately similar number of procedures between the sexes and an overall median age of 31 years. Overall, 86% (n = 2098) of the specimens included resection of the mesoappendix, and 58 (2.4%) appendiceal neoplasms were identified. Of them, 33 (1.3%) specimens included neuroendocrine appendiceal neoplasms. Eleven (33%) patients with appendiceal neuroendocrine neoplasms were recommended ORH. One of these patients may have avoided additional surgery, whereas 3 (9.1%) patients with tumours of 10-20 mm avoided ORH because their mesoappendix was resected. At our centre, there has been a significant change in the practice of mesoappendix resection, and we support resection of the mesoappendix during appendicectomy. The procedure is technically straightforward and safe, incurs no increases in costs or time, allows for accurate tumour staging and guides decisions regarding further surgical interventions.


When 3D genome changes cause disease: the impact of structural variations in congenital disease and cancer.
Large structural variations (SV) are a class of mutations that have long been known to cause a wide range of genetic diseases, from rare congenital disease to cancer. Many of these SVs do not directly disrupt disease-related genes and determining causal genotype-phenotype relationships has been challenging to disentangle in the past. This has started to change with our increased understanding of the 3D genome folding. The pathophysiologies of the different types of genetic diseases influence the type of SVs observed and their genetic consequences, and how these are connected to 3D genome folding. We propose guiding principles for interpreting disease-associated SVs based on our current understanding of 3D chromatin architecture and the gene-regulatory and physiological mechanisms disrupted in disease.


The glycosylation defect in solute carrier SLC35A2/SLC35A3 double knockout cells is rescued by SLC35A2-SLC35A3 and SLC35A3-SLC35A2 hybrids.
SLC35A2 and SLC35A3 are homologous proteins with postulated nucleotide sugar transporting activities. Unlike SLC35A2, whose specificity for UDP-Gal is well-established, the UDP-GlcNAc transporting activity initially attributed to SLC35A3 has recently been put into question. In this study, we constructed two hybrid proteins (SLC35A2-SLC35A3 and SLC35A3-SLC35A2) and expressed them in a previously generated SLC35A2/SLC35A3 double knockout HEK293T cell line. Our idea was to force equivalent stoichiometry of the two proteins in the cells in order to reproduce the behavior of the SLC35A2/SLC35A3 complexes in the Golgi membrane. The hybrid proteins were able to fully restore glycosylation in the double knockout. In contrast, the expression of SLC35A3 alone in these cells improved galactosylation only to a limited extent. Our study shows that the proper glycosylation requires a balanced cooperation between SLC35A2 and SLC35A3.


Influence of treatment modalities of prepared teeth on retention of cast metal copings bonded with self-adhesive resin cements.
To evaluate the influence of different conditioning methods of prepared teeth on the retention of cast metal copings bonded with two self-adhesive resin cements. Mandibular first molars (n = 80) were prepared to receive metal copings. Sixteen molars were stored in water without interim copings as a control group (CG), while 64 molars were covered with interim copings. Eighty cast copings were laboratory fabricated from Ni-Cr alloy. Interim copings were removed, and 64 molars were cleaned and divided into four groups (n = 16) according to pretreatment methods of prepared molars: no pretreatment (T-NT) and conditioning with self-etching adhesive (T-SE), polyacrylic acid (T-PA), or ethylenediaminetetraacetic acid (EDTA) (T-ED). Each group was further subdivided into two subgroups (n = 8) according to luting cements. RelyX Unicem and seT self-adhesive resin cements were used for cementation of copings. Specimens were stored in water at 37°C for 6 months and then cyclically loaded and thermal cycled. Retentive stress in N was recorded for each specimen. Statistical analyses were conducted with two- and one-way ANOVA and Tukey HSD test. Retentive stress ranged from 526.7 to 692.9 N for RelyX Unicem and 339.8 to 492.3 N for seT. There were no statistically significant differences between the mean retentive stress of the CG, T-SE, and T-PA groups (P > .05). The mean retentive stress of group CG was significantly higher than mean retentive stress of groups T-NT and T-ED (P < .05). The mean retentive stress of the control and test groups bonded with RelyX Unicem was significantly higher than the mean retentive stress of the same groups bonded with seT. Conditioning of prepared teeth using polyacrylic acid or self-etching adhesive significantly increased the retentive stress of cast metal copings.


Merging two gene-expression studies via cross-platform normalization.
Gene-expression microarrays are currently being applied in a variety of biomedical applications. This article considers the problem of how to merge datasets arising from different gene-expression studies of a common organism and phenotype. Of particular interest is how to merge data from different technological platforms. The article makes two contributions to the problem. The first is a simple cross-study normalization method, which is based on linked gene/sample clustering of the given datasets. The second is the introduction and description of several general validation measures that can be used to assess and compare cross-study normalization methods. The proposed normalization method is applied to three existing breast cancer datasets, and is compared to several competing normalization methods using the proposed validation measures. The supplementary materials and XPN Matlab code are publicly available at website: https://genome.unc.edu/xpn


We've got mail.
The letters section of the British Dental Journal has always been one of the most popular sections, confirmed yet again by our latest Readership Survey. This is possibly because letters are an instant reflection of popular opinion as well as an opportunity for research to be checked and questioned by those in the field.


The characteristics, tumorigenicities and therapeutics of cancer stem cells based on circRNAs.
Currently, recurrence and metastasis are still the main causes leading to the failure of various therapies for malignant tumors. In view of this, research on cancer stem cells (CSCs) has received increasing attention. CSCs are a subgroup of cancer cells with the characteristics of self-renewal, multidirectional differentiation, and immortal proliferation, and are closely related to resistance, metastasis, and recurrence. Circular RNAs (circRNAs) are a type of noncoding RNA (ncRNA) containing a covalent closed loop and are characterized by their abundance, stability, conservation, and tissue specificity. In this article, we focus on the characteristics of CSCs and review the latest research advances on the role of circRNAs in CSCs.


Does moderate tricuspid regurgitation require attention during mitral valve surgery?
This study aims to determine whether tricuspid regurgitation (TR) ≥ 2+ requires attention during mitral valve surgery. From April 1999 to 2009, 161 patients undergoing primary, isolated mitral valve procedures were assessed. Preoperative moderate TR (≥2+) was present in 56 of 161 patients and tricuspid valve repair (TVR: ring annuloplasty) was carried out on 22 of 56 patients with TR ≥ 2+. Baseline echocardiogram included TR severity (ASE criteria), TR velocity, estimated right atrial pressure, visual assessment of right ventricular failure and strain. Follow-up was 47 ± 33 months (96% complete); 91 of 161 patients overall (57%) and 44 of 45 patients with TR ≥ 2+ had follow-up echocardiogram. Patients with moderate TR had worse baseline functional class and operative risks, both worst in the non-TVR group. Overall mortality was 15% (n = 23), comprising 2.5% (4/161) 30-day mortality and 12% (9/157) late death. Poorer preoperative TR was associated with worse survival by univariate analysis (P = 0.046), after correction for right ventricular function and pulmonary artery pressure (P = 0.049), age and diabetes (P = 0.041). Despite lower risk of TR ≥ 2+ with TVR, 5-year survival was 42%, which was less than TR < 2+ and that of non-TVR group (90%, P = 0.003). Improvement in overall functional class (NYHA) was better in the non-TVR group (TVR: preoperative 2.1 ± 1.5; post-operative 1.2 ± 1.1 (P = 0.02) versus non-TVR: preoperative 1.8 ± 1.4, post-operative 1.2 ± 0.9 (P < 0.0001)). There was no difference in quality of life (QOL) indices (SF-36 questionnaire) at follow-up between patients with TR < 2+ and TR ≥ 2+ preoperatively, or across all levels of TR before or after surgical repair. Preoperative TR ≥ 2+, non-TVR group had more favourable functional class and mid-term survival with comparable QOL and echocardiographic parameters to the TVR group.


Endoscopic therapy of bleeding gastrointestinal hemangiomas and angiodysplasia.
A variety of vascular lesions may be found in the gastrointestinal tract. They make up a small but significant percentage of all gastrointestinal bleeders, especially from the colon. New endoscopic techniques have made therapy as well as diagnosis possible. In order to fully use this modality we must understand the incidence, pathology, distribution, and pathophysiology of these lesions. Types of treatment presently available will be discussed.


A microdialysis study investigating the mechanisms of hydroxyl radical formation in rat striatum exposed to glutamate.
Considerable evidence has linked hydroxyl radicals (.OH) to excitotoxicity. Glutamate infused through a microdialysis probe into rat striatum induced a massive .OH production, which was completely blocked by PBN and attenuated by dizocilpine, 2-amino-5-phosphonopentanoic acid (AP-5), NG-nitro-L-arginine methyl ester (L-NAME) and mepacrine. Thus, we suggest that the neurotoxic effects of glutamate in vivo may derive from an increased formation of .OH resulting from excessive activation of NMDA receptors and downstream enzymes such as NOS and PLA2.


Introducing a cell moisturizer: organogel nano-beads with rapid response to electrolytes for Prussian white analogue based non-aqueous potassium ion battery.
Prussian white analogue nanoparticles were connected internally by a composite consisting of poly(butyl methacrylate) (PBMA) nano-gel and a conducting polymer layer via a one-step route. The powder falling problems have been mitigated by the intrinsic good binding strength of PBMA organogel; meanwhile, the conducting polymer provides extra transfer paths for electrons.


Activation of TMEM16A by natural product canthaxanthin promotes gastrointestinal contraction.
Transmembrane 16A (TMEM16A), also known as anoctamin 1, is the molecular basis of the calcium-activated chloride channels. TMEM16A is present in interstitial cells of Cajal, which are the pacemaker cells that control smooth muscle contraction. TMEM16A is implicated in gastrointestinal disorders. Activation of TMEM16A is believed to promote the gastrointestinal muscle contraction. Here, we report a highly efficient, nontoxic, and selective activator of TMEM16A, canthaxanthin (CX). The study using molecular docking and site-directed mutation revealed that CX-specific binging site in TMEM16A is K769. CX was also found to promote the contraction of smooth muscle cells in gastrointestinal tract through activation of TMEM16A channels, which provides an excellent basis for development of CX as a chemical tool and potential therapeutic for gastrointestinal dysfunction.


Influence of Tangeretin on the Exponential Regression of Inflammation and Oxidative Stress in Streptozotocin-Induced Diabetic Nephropathy.
Diabetes is an amalgamation of metabolic disorders marked by hyperglycemia. Over time diabetes brings up several other complications with it like cardiovascular disease, retinopathy, neuropathy, and nephropathy. among which diabetic nephropathy (DN) is the one we are concerned about in the present study. Diabetes management requires following a healthy lifestyle with proper medication. Most of the anti-diabetic drugs available at present come with adverse side effects. Nature has provided us with several components that are anti-diabetic in nature which has fewer or no side effects and tangeretin is one among them. Tangeretin is a natural flavonoid abundantly present in orange peel and tangerines. Our study is designed to evaluate tangeretin, as an anti-diabetic medication especially for patients suffering from diabetic nephropathy. The procured healthy rats were first divided into four groups: the group I was maintained as healthy control and the others were subjected to the induction of diabetes by i.p. injection of streptozotocin (STZ) at the concentration of 55mg/kg b.wt .Then, the diabetic rats were further divided into three groups: group II was used as the diabetic control rats and the group III and group IV were administered with tangeretin (25mg/kg b.wt) and positive control drug metformin (150mg/kg b.wt) for 8 weeks. The body weight, blood glucose, and serum insulin levels were estimated at week 0 and week 8. Reactive oxygen species (ROS) inhibitory effect, antioxidant, antilipidemic, nephroprotective, and anti-inflammatory effects of tangeretin on the diabetic-induced rats were evaluated at the end of week 8 in addition to the histopathological assessment of the sections of the kidneys of the experimental rats. All the test results concluded that tangeretin was able to significantly decelerate the progression of DN in STZ-induced diabetic rats.


Mild COVID-19 infection associated with post-COVID-19 condition after 3 months - a questionnaire survey.
The coronavirus disease 2019 (COVID-19), caused by infection with SARS-CoV-2, can lead to post-COVID-19 condition, a secondary syndrome of persistent and new post-acute symptoms, but evidence on this syndrome is still scarce. In a questionnaire survey, residents of the city of Bremen (Germany) with verified SARS-CoV-2 infection were invited to answer questions (online questionnaire or interview) concerning symptoms experienced at the time of infection and at the time of questionnaire completion at least three months later. Main outcome of the analysis was the presence of a post-COVID-19 condition at the time of the interview, defined as the presence of at least two of three leading symptoms: fatigue, breathing difficulties, or cognitive problems. A post-COVID-19 condition was more likely to be reported if respondents had, at the time of infection, suffered from fatigue (OR 1.75; 95% CI: 1.00, 3.06), breathing difficulties (OR 4.02; 95% CI: 2.80, 5.77), cognitive symptoms (OR 2.98; 95% CI: 1.48, 6.02), or head- & bone aches (OR 2.06; 95% CI: 1.25, 3.42). The odds of developing a post-COVID-19 condition increased with the number of symptoms at infection. Females were more likely to report a post-COVID-19 condition (OR 1.54; 95% CI: 1.05, 2.24). Analyzing only non-hospitalized respondents changed results only slightly. Our study adds to growing evidence that even a mild course of COVID-19 poses a risk for developing a post-COVID-19 condition. Females and those with initial symptoms including fatigue, breathing difficulties, and cognitive symptoms seem more likely to also experience post COVID-19 symptoms several months after infection.KEY MESSAGESEven a mild course of COVID-19 poses a risk for developing a post-COVID-19 condition.Females seem more likely to develop a post-COVID-19 condition.Those with initial symptoms including fatigue, breathing difficulties, and cognitive symptoms seem more likely to develop a post-COVID-19 condition.


Poly implant prothèse (PIP) breast implants: our experience.
This study describes our experience on the management of patients with PIP (Poly Implant Prothèse) breast implants between 2000 and 2008. The medical records of patients were reviewed. Data was collected on clinical presentation, investigations, management and outcome. 44 patients, with bilateral breast implants, and a median age of 33 years (18-54 years), were reviewed, and of these, 31 patients were asymptomatic. Symptoms at presentation included lymphadenopathy, capsule formation, breast lump, seroma and breast pain. Patients underwent mammography, ultrasound and MRI scanning of the breasts as part of the imaging investigations. 5 patients declined explantation. Reasons for explantation included patient anxiety, silent rupture, aesthetic breast change, palpable nodes and breast lump. 17 out of a total of 78 implants (21.8%) were noted to have ruptured; 2 had a simple tear and 15 were totally disintegrated. 1 patient underwent removal of the implants, 18 underwent exchange of implants, and 20 patients had a capsulotomy and exchange of implants. Postoperative complications included wound infection, seroma, axillary lymphadenopathy, hypersensitive scar and overgranulation of the wound. Our series confirms the high rate of PIP implant rupture (21.8%), the majority of which were asymptomatic. The main reasons for explantation were patient anxiety and silent rupture of implants. It is imperative that patients should be appropriately counselled, prior to surgery with regards to removal of the implants, given the increased rupture rates noted.


YAP/miR-524-5p axis negatively regulates TXNIP expression to promote chondrosarcoma cell growth.
Chondrosarcoma (CHS) is the second most common bone malignant tumor and currently has limited treatment options. We have recently demonstrated that thioredoxin interacting protein (TXNIP) plays a crucial role in the oncogenesis of bone sarcoma, yet its implication in CHS is underdetermined. In the present study, we first found that knockdown of TXNIP promotes the proliferation of CHS cell largely through increasing their glycolytic metabolism, which is well-known as Warburg effect for providing energy. Consistent with our previous report that YAP is fundamental for CHS cell growth, herein we revealed that YAP functioned as an upstream molecule of TXNIP, and that YAP negatively regulated TXNIP mRNA and protein expression both in vitro and in vivo. Mechanistically, although knockdown of YAP upregulated both the nuclear and cytoplasmic TXNIP expression, we did not observe any obvious interaction between YAP and TXNIP; instead, miRNA-524-5p was demonstrated to be required for YAP-regulated TXNIP expression and thus controlling CHS cell growth. Together, our study reveals that TXNIP is a tumor suppressor in terms of CHS, and that the YAP/miRNA-524-5p/TXNIP signaling axis may provide a novel clue for CHS targeted therapy.