Clinical Features and Expression Patterns for Burn Patients Developed Marjolin Ulcer.
Marjolin's ulcer is a type of skin cancer that generated from chronic nonhealing trauma. For years, its pathogenesis mechanisms remain unclear. Regarding this situation, the authors retrospectively analyze the patients admitted to their department from 2005 to 2019 to present several representative cases and examine the expression patterns of survivin and its role in this process. Among these patients, the latent period ranges from 2 to 25 years, with 8.43 years in average. There is no notable relationship between the latent period and age (P = .643 > .05). Therefore, Marjolijn's ulcer arises from extremities and joints more often compared with other parts (P < .05). The expression ratio of survivin in Marjolin's ulcer is significantly higher than that in skin ulcer (P < 0.05). And the expression ratio of survivin in patients diagnosed with Marjolin's ulcer is also correlated with lymphatic metastasis (P < .05). Frequent follow-ups and prompt diagnosis and management are necessary as the prognosis is poor for patients with metastasis. Survivin may be a potential target for future development of target therapy in order to maximize the efficacy and improve the quality of life for patients suffering from Marjolin's ulcer.


Characterization, biomedical and agricultural applications of protease inhibitors: A review.
This review describes Protease Inhibitors (PIs) which target or inhibit proteases, protein digesting enzymes. These proteases play a crucial task in many biological events including digestion, blood coagulation, apoptosis etc. Regardless of their crucial roles, they need to be checked regularly by PIs as their excess may possibly damage host organism. On basis of amino acid composition of PIs where Protease-PI enzymatic reactions occur i.e. serine, cysteine, and aspartic acid, they are classified. Nowadays, various PIs are being worked upon to fight various parasitic or viral diseases including malaria, schistosomiasis, colds, flu', dengue etc. They prevent an ongoing process begun by carcinogen exposure by keeping a check on metastasis. They also possess potential to reduce carcinogen-induced, increased levels of gene amplification to almost normal levels. Some PIs can principally be used for treatment of hypertension and congestive heart failure by blocking conversion of angiotensin I to angiotensin II for example Angiotensin-converting enzyme inhibitors (ACEIs). Also PIs target amyloid β-peptide (Aβ) level in brain which is prime responsible for development of Alzheimer's Disease (AD). Also, PIs inhibit enzymatic activity of HIV-1 Protease Receptor (PR) by preventing cleavage events in Gag and Gag-Pol that result in production of non-virulent virus particles.


A patient with severe black fly (Simuliidae) hypersensitivity referred for evaluation of suspected immunodeficiency.
Biting flies of the Diptera order and specifically the black fly (Simuliidae family) can be rare causes of severe hypersensitivity reactions. To describe a patient referred for evaluation of immunodeficiency whose clinical course is explained by severe Simuliidae hypersensitivity. The patient's immune system was investigated using standard laboratory evaluations. Hypersensitivity to Simuliidae was pursued because of historical features of her presentation and was specifically examined by skin prick and intradermal testing with whole body extract. The patient's history was notable for recurrent and severe seasonal episodes of presumed cellulitis after black fly bites that responded poorly to intravenous antibiotics. One episode was followed by acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome) and another by minimal change nephrotic syndrome. The results of immunologic investigations were unremarkable, but cutaneous hypersensitivity to Simuliidae was demonstrated with a 6.5-mm wheel and 35-mm flare reaction to intradermal injection of only 0.0005 microg of whole body extract. Similar to Hymenoptera, Simuliidae can rarely result in extreme hypersensitivity and should be considered in appropriate cases. This patient illustrates how severe reactions toinsect bites can be misdiagnosed.


Passive heating following the prematch warm-up in soccer: examining the time-course of changes in muscle temperature and contractile function.
This study examined changes in muscle temperature, electrically evoked muscle contractile properties, and voluntary power before and after a soccer specific active warm-up and subsequent rest period. Ten amateur soccer players performed two experimental sessions that involved performance of a modified FIFA 11+ soccer specific warm-up, followed by a 12.5-min rest period where participants were required to wear either normal clothing or a passive electrical heating garment was applied to the upper thigh muscles. Assessments around the warm-up and cool-down included measures of maximal torque, rate of torque development, muscle temperature (Tm), and electrically evoked measures of quadriceps contractile function. Tm was increased after the warm-up by 3.2 ± 0.7°C (P < 0.001). Voluntary and evoked rates of torque development increased after the warm-up between 20% and 30% (P < 0.05), despite declines in both maximal voluntary torque and voluntary activation (P < 0.05). Application of a passive heating garment in the cool-down period after the warm-up did not effect variables measured. While Tm was reduced by 1.4 ± 0.4°C after the rest period (P < 0.001), this value was still higher than pre warm-up levels. Voluntary and evoked rate of torque development remained elevated from pre warm-up levels at the end of the cool-down (P < 0.05). The soccer specific warm-up elevated muscle temperature by 3.2°C and was associated with concomitant increases of between 20% and 30% in voluntary rate of torque development, which seems explained by elevations in rate-dependent measures of intrinsic muscle contractile function. Application of a passive heating garment did not attenuate declines in muscle temperature during a 12.5-min rest period.


The binding of peroxidase-labelled lectins to human breast epithelium. III--Altered fucose-binding patterns of breast carcinomas and their significance.
Tissue sections from 80 human breast carcinomas have been examined for evidence of binding of the two fucose-specific lectins, Lotus tetragonolobus and Ulex europeus I, with enzymes utilized as an indicator system. Both single-staining and double-staining methods (Lotus tetragonolobus-peroxidase and Ulex europeus I-alkaline phosphatase) have been employed. In contrast to normal breast in which there is consistent reactivity of all epithelium with Lotus tetragonologus a variable loss of binding has been found within carcinomas. Surprisingly, this bears no relationship to tumour differentiation; nor does it correlate with local lymph node metastasis. Ulex europeus I has a variable reactivity with carcinomas, as it does with normal breast epithelium, and this likewise has no correlation with differentiation. However, a relationship has been found between specific patterns of binding and axillary lymph node status. The value of using two lectins with the same major sugar specificity but having different binding affinities is illustrated in this study, in which differences in behavioural characteristics have been identified between fucose-containing glyco-conjugates having minor structural variations.


Establishing the psychometric properties of constructs from the conceptual 'Settlement Services Literacy' framework and their relationship with migrants' acculturative stress in Australia.
Effective migration often requires supports for new arrivals, referred to as settlement services. Settlement services literacy (SSL) is key to ensuring new migrants have the capability to access and utilise the information and services designed to support the resettlement process and achieve positive settlement outcomes. To date, however, no research has sought to empirically validate measures of SSL or to assess individual migrants' levels of SSL. The aim of this study was to establish the psychometric properties of constructs from the conceptual SSL framework. Using a snowball sampling approach, trained multilingual research assistants collected data on 653 participants. The total sample was randomly divided into two split-half samples: one for the exploratory factor analysis (EFA; N = 324) and the other for the confirmatory factor analysis (CFA; N = 329) and scale validation. The final SSL scale included 30 questions. The full data set was used to test the nomological validity of the scale regarding whether the components of SSL impact on migrants' level of acculturative stress. The EFA yielded five factors: knowledge (eight items, α = 0.88), empowerment (five items, α = 0.89), competence (four items, α = 0.86), community influence (four items, α = 0.82), and political (two items, α = 0.81). In the CFA, the initial model demonstrated a poor to marginal fit model. Its re-specification by examining modification indices resulted in a good model fit: CMIN/DF = 3.07, comparative fit index = 0.92, root mean square error of approximation = 0.08 and standardised root mean square residual = 0.07, which are consistent with recommendations. All the path coefficients between the second-order construct (SSL) and its five dimensions (knowledge, empowerment, competence, community influence and political) were significant at an α = .05 level, giving evidence for the validity of different SSL dimensions. We found that SSL is significantly related to migrants' acculturative stress (β = - 0.39, p < 0.05) in the nomological model. The study provides evidence of the construct validity and reliability of the SSL tool. It provides the basis for integrating the measures of SSL into evaluation of settlement services. This will allow for more effective decision-making in designing and implementing settlement services as well as funding and service agreements to address any deficiencies.


Non-Genetic Intra-Tumor Heterogeneity Is a Major Predictor of Phenotypic Heterogeneity and Ongoing Evolutionary Dynamics in Lung Tumors.
Impacts of genetic and non-genetic intra-tumor heterogeneity (ITH) on tumor phenotypes and evolvability remain debated. We analyze ITH in lung squamous cell carcinoma at the levels of genome, transcriptome, and tumor-immune interactions and histopathological characteristics by multi-region bulk and single-cell sequencing. Genomic heterogeneity alone is a weak indicator of intra-tumor non-genetic heterogeneity at immune and transcriptomic levels that impact multiple cancer-related pathways, including those related to proliferation and inflammation, which in turn contribute to intra-tumor regional differences in histopathology and subtype classification. Tumor subclones have substantial differences in proliferation score, suggestive of non-neutral clonal dynamics. Proliferation and other cancer-related pathways also show intra-tumor regional differences, sometimes even within the same subclones. Neo-epitope burden negatively correlates with immune infiltration, indicating immune-mediated purifying selection on somatic mutations. Taken together, our observations suggest that non-genetic heterogeneity is a major determinant of heterogeneity in histopathological characteristics and impacts evolutionary dynamics in lung cancer.


Sex differences and estrous cycle dependent variation in rotational behavior elicited by electrical stimulation of the mesostriatal dopamine system.
In this study electrical stimulation-induced rotational behavior was used as a behavioral index of mesostriatal dopamine (DA) activity to investigate gender and hormonal influences on the DA system. In female rats we found estrous cycle related variations in electrical stimulation-induced rotational behavior. A constant electrical stimulus produced significantly more turning on the day of estrus, than it did 24 h later, on diestrus 1. Gonadectomy attenuated contraversive rotational behavior in female, but not male rats. In contrast, ovariectomy had no effect on the ipsiversive rotational behavior produced by stimulation of the reticular formation. This evidence supports the idea that endogenous changes in gonadal hormone levels influence the functional activity of the mesostriatal DA system in a sexually dimorphic manner.


Structural rearrangements of chromosome 3 in 57 patients with acute myeloid leukemia: clinical, hematological and cytogenetic features.
Structural rearrangements of chromosome 3q have been described in approximately 2% of patients with acute myeloid leukemia. Breakpoints are mainly located in the 3q21 and 3q26 regions but may occur elsewhere on chromosome 3. To determine the relationship between these breakpoints and the hematological parameters, including outcome of these patients, we analysed data from newly diagnosed adult AML patients with 3q rearrangements referred to our institution over a 15-year period. This retrospective study was conducted using data from 57 AML patients (median age: 64 years, range 19-82) with 3q rearrangements. Cytogenetic analysis was performed using standard techniques (RHG banding, FISH). Data concerning AML patients with 3q abnormalities were compared for outcome with those from patients with normal karyotype and from patients with 5q deletion, treated according to the same intensive protocols for the same time period. Patients with myeloid malignancy displaying 3q rearrangement were assigned to five subgroups, including those with: 3q21/q26 rearrangement; 3q21 alone, including t(1;3)(p36;q21); 3q26 alone, resulting in translocations involving multiple chromosome partners; t(3;5); 3q deletions. Among these patients, 37 were treated in AML chemotherapy trials. Complete remission was achieved in 43% (26/57) of cases. Five patients died early. Sixteen patients were resistant to induction chemotherapy. Median DFS and median OS were 4.5 and 8.8 months respectively. Relapse was observed in 34% of patients achieving CR. Comparison of the outcome of CR patients with that of patients presenting with normal karyotype (intermediate-risk) or complete/partial 5q deletion (high-risk) confirmed the very poor prognosis of patients carrying 3q chromosomal rearrangements. These data confirm that 3q rearrangements at q21 or q26 are recurring chromosomal abnormalities in AML. Appearing frequently in combination with monosomy 7 and an abnormal megakaryopoiesis, patients with these abnormalities have a particularly poor prognosis.


Sodium valproate effect on the structure of rat glandule thymus: Gender-related differences.
Sodium valproate (VPA) was shown to inhibit cell growth mechanisms such as cell cycle arrest, proliferation suppression, increase of apoptosis. Many aspects of the contribution of the VPA pharmacological mechanisms and their significance in gender-related processes have not been investigated. In our study, we have tested hypothesis that the influence of VPA on thymus weight and structure might be gender-related. The thymus of Wistar rats of both genders aged 8 weeks was investigated in the following groups (n = 6 each): controls, treated with VPA, castrated male and female treated with VPA, and the castrated control of both genders. The thymus weight, structural changes and area of cortical and medullar parts of the gland in slides stained with hematoxylin and eosin and immunohistochemically were assessed. A comparison of thymus weight of castrated male and of castrated VPA-treated male rats showed a significant thymus weight loss after VPA treatment (0.66 ± 0.04 g vs. 0.43 ± 0.03 g, p < 0.05). The treatment with VPA caused an about 6-fold (0.39 ± 0.12 vs. 0.07 ± 0.03) increase of Hassall's corpuscles (HCs) numbers per 1mm(2) in male and more than 4-fold increase (0.46 ± 0.07 vs. 0.10 ± 0.04) in female rats. In castrated males and females, the HCs number was also increased, but this increase was statistically significant only in male animals vs. controls (0.46 ± 0.10 vs. 0.07 ± 0.03, p < 0.001 in males; 0.29 ± 0.13 vs. 0.10 ± 0.04, p > 0.05 in females). When castrated male and female rats were treated with VPA, further increase of HC numbers was found. In our study, VPA has inhibited the proliferative capacity of thymocytes by diminishing the thymus weight and inducing a differentiation of thymic medullar epithelial cells into HCs. The diminishing of the gl. thymus weight under the influence of VPA was significant in castrated male rats. The number of HCs increased in animals of both genders under the influence of VPA. Gender differences in HCs development were noted in castrated animals.


Tubes and foraging behavior in larval Chironomidae: implications for predator avoidance.
In laboratory experiments, I studied differential susceptibility of four co-occurring species of chironomids to a predatory damselfly. The chironomids differed in foraging behavior and could be ranked according to the amount of time they spent outside of their tubes. In choice experiments, the predator consistently selected the prey which spent more time out of the tube, and time out of tube was a significant predictor of the predation rate coefficient. Electivity indices, calculated from field samples and diet analyses of the predator, supported the laboratory results. The data suggest that exposure to predators in a heterogeneous prey community is largely determined by tubedwelling behavior.


Reactivity to thought-shape fusion in adolescents: the effects of obesity status.
Thought-shape fusion (TSF) is a cognitive distortion associated with eating pathology. TSF is a phenomenon associated with perceptions of weight gain, body dissatisfaction and moral wrongdoing after merely thinking about consumption of high-caloric foods. Women who are overweight are less susceptible to inductions of TSF than are women who are normal-weight. Obese adolescents were less susceptible to a TSF induction than were lean adolescents (i.e., they reported lower state TSF in comparison with lean adolescents, and did not demonstrate an increase in state TSF relative to a neutral induction). Eating pathology, but not obesity status or gender, predicted trait TSF. Previous research has demonstrated that imagining consumption of high-caloric foods can lead to feelings of guilt, and perception of weight gain and moral wrongdoing. This psychological response is known as thought-shape fusion (TSF). This study was conducted to assess the susceptibility of obese and lean adolescents to TSF. To investigate TSF susceptibility in adolescents, and predictors of this distortion, a total of 82 adolescents (44 obese and 38 lean) were randomly assigned to receive either a TSF or a neutral induction. Subsequent TSF reactivity was assessed (i.e., levels of state TSF after the induction), as was trait TSF, eating pathology and depression. The results suggest that obese adolescents are less susceptible to TSF than are lean adolescents, as lean (but not obese) adolescents reported significantly higher state TSF relative to participants who received the neutral induction. Similarly, lean adolescents who were exposed to a TSF induction reported higher state TSF than did obese adolescents. Furthermore, obesity did not emerge as a predictor of trait TSF. Factors that may account for decreased TSF susceptibility in obese adolescents relative to lean adolescents will be discussed.


Transcendental Meditation practitioners show reduced expression of the Conserved Transcriptional Response to Adversity.
A recent exploratory study of transcriptional effects of long-term practice of Transcendental Meditation (TM) technologies found evidence for altered expression of genes associated with health and disease. In the present secondary analysis of those data, we test the more specific hypothesis that this sample of long-term practitioners shows a significant reduction in markers of the "Conserved Transcriptional Response to Adversity" (CTRA), an RNA profile characterized by up-regulated inflammation and down-regulated Type I interferon (IFN) activity. Data come from a previously published study providing genome-wide transcriptional profiles of peripheral blood mononuclear cells (PBMC) from healthy, 38-year practitioners of TM technologies and matched controls (n = 12, mean age 65). The current analysis specifically tests for differential expression of a previously established CTRA indicator gene score, with cross-validation by promoter-based bioinformatic analysis of CTRA-typical differences in transcription factor activity and monocyte subset cellular origins. Compared to controls, the TM group showed lower expression of a pre-specified set of CTRA indicator genes. These effects were accompanied by genome-wide indications of down-regulated pro-inflammatory transcription factor activity (NF-κB, AP-1), up-regulated activity of Interferon Response Factors (IRF) and reduced transcriptional activity of classical monocytes. Conclusions: A sample of long-term practitioners of TM showed reduced CTRA gene expression in PBMC compared to matched controls, supporting the likely value of further research to evaluate causality and specificity of this potential mechanism of health benefits in meditators.


What is the optimal postoperative sagittal alignment in ankylosing spondylitis patients with thoracolumbar kyphosis following one-level pedicle subtraction osteotomy?
Radiographic realignment objectives for the surgical correction of adult spinal deformity (ASD) have been well-described. However, the optimal sagittal spinopelvic alignment after corrective osteotomy for thoracolumbar kyphosis secondary to ankylosing spondylitis (AS) is still unknown so far. To comprehensively investigate the relationship between radiographic parameters and clinical outcomes measured by Oswestry Disability Index (ODI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in thoracolumbar kyphosis patients caused by AS following one-level pedicle subtraction osteotomy (PSO) and to determine the optimal sagittal alignment at a minimum of 2-year follow-up. A retrospective review of consecutive AS patients from one institution (2006-2016). One hundred AS-related thoracolumbar kyphosis patients who underwent one-level PSO with a minimum of 2-year follow-up (range, 2-10 years). Spinopelvic parameters at final follow-up (≥2 years) included thoracic kyphosis, lumbar lordosis, osteotomized vertebra angle, pelvic tilt (PT), sacral slope (SS), pelvic incidence, sagittal vertical axis, spinosacral angle (SSA), T1 pelvic angle (TPA), spinopelvic angle (SPA), and global kyphosis. Clinical outcomes at final follow-up (≥2 years) was evaluated by ODI and BASDAI, and ODI<20 was defined as good clinical outcome. Pre- and postoperative radiographic and clinical outcomes were compared by paired samples t test. The correlation between the postoperative radiographic parameters and clinical outcomes was investigated by Pearson correlation analysis. Linear regression analysis was performed to construct predictive models of the clinically relevant radiographic parameters based on ODI scores and to determine the realignment goals. Multiple stepwise regression analysis was applied to figure out the major radiographic contributors of ODI score at the final follow-up. In total, 100 AS patients (92 males and 8 females) with a mean age of 34.7±9.5 years (range, 17-63 years) were followed up for 38.6±17.5 months (range, 24-120 months). At the final follow-up, PT and TPA were positively correlated with both ODI and BASDAI score (p<.05). Although SS, SSA, and SPA were negatively associated with the score of ODI (p<.05), and BASDAI was negatively related to SPA (p<.05). Predicting regression models of the clinically-relevant radiographic parameters were built based on the ODI score at the last follow-up. Based on the regression models, the optimal sagittal alignment of AS patients satisfying good clinical outcome (ODI<20) at a minimum of 2-year follow-up was: PT<24°, SSA>108°, TPA<22°, and SPA>152°. Realizing the aforementioned realignment goals may contribute to satisfied clinical outcome for AS patients with thoracolumbar kyphosis undergoing one-level PSO.


What is the distribution of trunk impairments and its relationship with disability level in individuals with multiple sclerosis?
Trunk control is essential for movement, balance and walking and is ignored in the regular medical follow-up. First, to describe the distribution of trunk impairments in the full range of disability levels in individuals with MS. Second, to identify the relationship between trunk control, measured by the Trunk Impairment Scale (TIS 2.0.), and general disability measured by the Expanded Disability Status Scale (EDSS). 154 individuals with MS were included (mean age 53.6; SD 11.06), EDSS ranging from 1.0- 8.5 (mean 4.47; SD 2.55). The relationship between EDSS and TIS 2.0. was calculated by Spearman correlation coefficient for the total sample and subgroups, EDSS ≤ 4 versus EDSS ≥ 4.5. Trunk impairments were detected throughout the full range of disability, including individuals with low disability. Pelvic elevation and lower trunk rotation appeared most difficult to perform. In the total sample, a moderate correlation was found (rho= -0.608**) between disability (EDSS) and trunk performance (TIS 2.0.). Sub-analyses revealed a poor correlation (rho= -0.193) for the EDSS ≤ 4 subgroup and a strong correlation for the EDSS ≥ 4.5 subgroup (rho= -0.712**). The results advocate for including trunk assessment already at early disease stages of MS, particularly of pelvic elevation and trunk rotation, and dedicated rehabilitation strategies.


Audiometric, vestibular, and genetic aspects of a DFNA9 family with a G88E COCH mutation.
To perform genetic analysis and to analyze cochleovestibular impairment features in a newly identified Dutch family with nonsyndromic autosomal dominant hearing impairment (DFNA9). Genetic analysis was performed using microsatellite markers and single nucleotide polymorphisms. Audiometric data were collected and analyzed longitudinally. Results were compared with those obtained in previously identified P51S COCH mutation carriers (n = 74). Special attention was also given to a comparison of age-related features such as progressive hearing loss and vestibular impairment. Tertiary referral center. G88E COCH mutation carriers from a Dutch family. The study of clinical features of a DFNA9 family carrying a G88E COCH mutation and to compare this to the symptoms of those carrying a P51S/COCH mutation. Pure-tone thresholds, phoneme recognition scores, and vestibular responses of the G88E mutation carriers were essentially similar to those previously established in the P51S mutation carriers. Hearing started to deteriorate in G88E mutation carriers from age 46 to 49 years and onward, whereas deterioration of vestibular function started from approximately age 46 years. In the P51S mutation carriers, vestibular impairment started earlier, at approximately age 34 years. However, the difference in age of onset with the G88E mutation carriers was not significant. Remarkably, the proportion of patients who developed complete vestibular areflexia within the age range of 40 to 56 years was significantly lower for the G88E mutation carriers than for the P51S mutation carriers. Apart from a significantly lower frequency of vestibular areflexia between the ages of 40 and 56 years, there are no phenotypic differences between carriers of the G88E and P51S mutations in the COCH gene.


High efficacy of chlorfenapyr-based net Interceptor® G2 against pyrethroid-resistant malaria vectors from Cameroon.
The increasing reports of resistance to pyrethroid insecticides associated with reduced efficacy of pyrethroid-only interventions highlight the urgency of introducing new non-pyrethroid-only control tools. Here, we investigated the performance of piperonyl-butoxide (PBO)-pyrethroid [Permanet 3.0 (P3.0)] and dual active ingredients (AI) nets [Interceptor G2 (IG2): containing pyrethroids and chlorfenapyr and Royal Guard (RG): containing pyrethroids and pyriproxyfen] compared to pyrethroid-only net Royal Sentry (RS) against pyrethroid-resistant malaria vectors in Cameroon. The efficacy of these tools was firstly evaluated on Anopheles gambiae s.l. and Anopheles funestus s.l. from Gounougou, Mibellon, Mangoum, Nkolondom, and Elende using cone/tunnel assays. In addition, experimental hut trials (EHT) were performed to evaluate the performance of unwashed and 20 times washed nets in semi-field conditions. Furthermore, pyrethroid-resistant markers were genotyped in dead vs alive, blood-fed vs unfed mosquitoes after exposure to the nets to evaluate the impact of these markers on net performance. The XLSTAT software was used to calculate the various entomological outcomes and the Chi-square test was used to compare the efficacy of various nets. The odds ratio and Fisher exact test were then used to establish the statistical significance of any association between insecticide resistance markers and bed net efficacy. Interceptor G2 was the most effective net against wild pyrethroid-resistant An. funestus followed by Permanet 3.0. In EHT, this net induced up to 87.8% mortality [95% confidence interval (CI): 83.5-92.1%) and 55.6% (95% CI: 48.5-62.7%) after 20 washes whilst unwashed pyrethroid-only net (Royal Sentry) killed just 18.2% (95% CI: 13.4-22.9%) of host-seeking An. funestus. The unwashed Permanet 3.0 killed up to 53.8% (95% CI: 44.3-63.4%) of field-resistant mosquitoes and 47.2% (95% CI: 37.7-56.7%) when washed 20 times, and the Royal Guard 13.2% (95% CI: 9.0-17.3%) for unwashed net and 8.5% (95% CI: 5.7-11.4%) for the 20 washed net. Interceptor G2, Permanet 3.0, and Royal Guard provided better personal protection (blood-feeding inhibition 66.2%, 77.8%, and 92.8%, respectively) compared to pyrethroid-only net Royal Sentry (8.4%). Interestingly, a negative association was found between kdrw and the chlorfenapyr-based net Interceptor G2 (χ2 = 138; P < 0.0001) with homozygote-resistant mosquitoes predominantly found in the dead ones. The high mortality recorded with Interceptor G2 against pyrethroid-resistant malaria vectors in this study provides first semi-field evidence of high efficacy against these major malaria vectors in Cameroon encouraging the implementation of this novel net for malaria control in the country. However, the performance of this net should be established in other locations and on other major malaria vectors before implementation at a large scale.


Are dogs indeed susceptible to Kanizsa's triangle illusion?
Survival often depends on the ability of the visual system to process information accurately; thus, research demonstrating that a brain is susceptible to optical illusions is of considerable interest, particularly when the experiments involve phylogenetic comparisons. Are Lõoke et al.'s (Anim. Cogn, 25:43-51, 2022) data strong enough to allow the inclusion of dogs on the list of nonhumans that can perceive illusory Kanizsa figures?


Metamorphosis of the central nervous system of Trichogramma telengai (Hymenoptera: Trichogrammatidae).
During metamorphosis, the insect CNS undergoes both structural and allometric changes. Due to their extreme de-embryonization and parasitism, the formation of the CNS in egg parasitoids occurs at the late larval stage. Our study provides the first data on the morphological and volumetric changes of the CNS occurring during the pupal development of the parasitic wasp Trichogramma telengai Sorokina, 1987 (Trichogrammatidae). The prepupal-pupal development includes fusion and concentration of ganglia achieved by the loss of connectives. Volumetric analysis shows that during the pupal development the absolute body volume and CNS volume gradually decrease. The brain and thoracic synganglion slightly increase in volume during the pupal period and extremely decrease from late pupa to adult. The CNS neuropil volume increases from prepupa to adult. The mean cell diameter also decreases during the metamorphosis of the nervous system. The cell body rind volume decreases during pupal development; this decrease correlates with the decrease in the number of cells on the one hand and increase in the neuropilar volume on the other hand.


[Agenda 2030 in Argentina: perceptions of health experts, comparison with the perceptions of Brazilian experts and the first impacts of the COVID-19 Pandemic].
The 2030 Agenda - a strategy of the United Nations Organization (UN) to promote global and sustainable human development capable of satisfying basic social needs - is still in the initial stages in most of the countries of South America. The scope of this investigation was to consult a group of health experts on the possibilities of Argentina fulfilling the 2030 Agenda, especially the goals of ODS3 - Health and Wellbeing - when they were consulted on obstacles, challenges, and policy recommendations to meet the goals. The change of management of the government in December 2019, and the outbreak of the Covid-19 pandemic in 2020, broadened the investigation incorporating the analysis of the incumbent Minister of Health of the Nation on the 2030 Agenda, the study carried out and the current perspectives in the pandemic period. The results were analyzed from a comparative standpoint with a Brazilian study, which revealed that most experts agree on the country's potential to meet the goals of the 2030 Agenda. However, in the analysis of the new Minister of Health, there are "the paradoxes of the pandemic" that relate to the opportunity to empower the health system pursuant to the Covid-19 pandemic.


Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study.
Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).


Prevalence and severity of atherosclerosis in different arterial territories and its relation with obesity.
There is uneven association between obesity, traditional risk factors, and cardiovascular events. We aimed to analyze the relation between cardiovascular risk factors, including obesity, with the severity of atherosclerosis in different arterial territories. Arteries from five territories (circle of Willis, carotids, coronaries, aorta, and renal) were taken from 185 persons, newborn to 90 years undergoing autopsy in the Forensic Medical Service in Mexico City, to determine atherosclerotic lesions by histopathological study. Lesions were classified according to the American Heart Association grading system as early (types I-III) and advanced (types IV-VI). The degree of atherosclerosis was correlated with arterial territories and risk factors. Frequencies of advanced lesions according to arterial territories were as follows: circle of Willis, 28%; right carotid, 36%; left carotid, 25%; right coronary, 71%; left coronary, 85%; right renal, 26%; left renal, 29%; and aorta, 52%; P=.0001, for all analyses. There was a higher risk for advanced lesions with increasing body mass index (BMI) (P=.004). However, after adjusting for age, gender, smoking status, hypertension, and diabetes mellitus, BMI was not independently associated with advanced lesions. Coronary arteries are significantly more affected than other arterial territories regardless of risk factors, showing the effect of local and systemic factors in the severity of atherosclerosis. We did not find an independent association between advanced atherosclerotic lesions and obesity.


Regulation of Cell Fate Decisions in Early Mammalian Embryos.
Early embryogenesis is characterized by the segregation of cell lineages that fulfill critical roles in the establishment of pregnancy and development of the fetus. The formation of the blastocyst marks the emergence of extraembryonic precursors, needed for implantation, and of pluripotent cells, which differentiate toward the major lineages of the adult organism. The coordinated emergence of these cell types shows that these processes are broadly conserved in mammals. However, developmental heterochrony and changes in gene regulatory networks highlight unique evolutionary adaptations that may explain the diversity in placentation and in the mechanisms controlling pluripotency in mammals. The incorporation of new technologies, including single-cell omics, imaging, and gene editing, is instrumental for comparative embryology. Broadening the knowledge of mammalian embryology will provide new insights into the mechanisms driving evolution and development. This knowledge can be readily translated into biomedical and biotechnological applications in humans and livestock, respectively.


Differences in proprioception, muscle force control and comfort between conventional and new-generation knee and ankle orthoses.
The aim of this study was to compare muscle force control and proprioception between conventional and new-generation experimental orthoses. Sixteen healthy subjects participated in a single-blind controlled trial in which two different types of orthosis were applied to the dominant knee or ankle, while the following variables were evaluated: muscle force control (accuracy), joint position sense, kinesthesia, static balance as well as subjective outcomes. The use of experimental orthoses resulted in better force accuracy during isometric knee extensions compared to conventional orthoses (P=0.005). Moreover, the use of experimental orthoses resulted in better force accuracy during concentric (P=0.010) and eccentric (P=0.014) ankle plantar flexions and better knee joint kinesthesia in the flexed position (P=0.004) compared to conventional orthoses. Subjective comfort (P<0.001) and preference scores were higher with experimental orthoses compared to conventional ones. In conclusion, orthosis type affected static and dynamic muscle force control, kinesthesia, and perceived comfort in healthy subjects. New-generation experimental knee and ankle orthoses may thus be recommended for prophylactic joint bracing during physical activity and to improve the compliance for orthosis use, particularly in patients who require long-term bracing.


Corrigendum: Integrating a Statistical Topic Model and a Diagnostic Classification Model for Analyzing Items in a Mixed Format Assessment.
[This corrects the article DOI: 10.3389/fpsyg.2020.579199.].


Myelography: From Lipid-Based to Gadolinium-Based Contrast Agents.
Myelographic contrast media of various types have been used over the past 100 years. Many of the early contrast agents had significant toxicities. Gas myelography was tried, but the contrast between gas and soft tissue is poor. Pantopaque, an oil-based iodinated medium was successfully used for decades, but was not compatible with computed tomography (CT) scanning because it was viscous, insoluble, and caused streak artifact. The development of water-soluble agents allowed even distribution in the subarachnoid space and excellent depiction of spinal anatomy on post-myelographic CT scanning. Although invasive, myelography will remain a useful tool for the foreseeable future.


Pyoderma gangrenosum after totally implanted central venous access device insertion.
Pyoderma gangrenosum is an aseptic skin disease. The ulcerative form of pyoderma gangrenosum is characterized by a rapidly progressing painful irregular and undermined bordered necrotic ulcer. The aetiology of pyoderma gangrenosum remains unclear. In about 70% of cases, it is associated with a systemic disorder, most often inflammatory bowel disease, haematological disease or arthritis. In 25-50% of cases, a triggering factor such as recent surgery or trauma is identified. Treatment consists of local and systemic approaches. Systemic steroids are generally used first. If the lesions are refractory, steroids are combined with other immunosuppressive therapy or to antimicrobial agents. A 90 years old patient with myelodysplastic syndrome, seeking regular transfusions required totally implanted central venous access device (Port-a-Cath(R)) insertion. Fever and inflammatory skin reaction at the site of insertion developed on the seventh post-operative day, requiring the device's explanation. A rapid progression of the skin lesions evolved into a circular skin necrosis. Intravenous steroid treatment stopped the necrosis' progression. Early diagnosis remains the most important step to the successful treatment of pyoderma gangrenosum.


Craniosynostosis in a patient with a de novo 15q15-q22 deletion.
Interstitial deletions involving the chromosomal band 15q15 are very rare. A total of five cases were previously reported. Here another case of a 15q15.2-q22.2 deletion is reported, presenting with severe craniosynostosis of coronary, metopic, and sagittal sutures. The chromosome 15 with the 17.7-Mb deletion was of the paternal origin. A critical region for craniosynostosis may be located at the 734-kb segment at 15q15.2. Interestingly, the entire FBN1 gene was deleted in this patient.


Evaluation of the anxiolytic-like effect of NKP608, a NK1-receptor antagonist, in two rat strains that differ in anxiety-related behaviors.
NKP608, a selective NK1 receptor antagonist, has been shown to produce anxiolytic-like effects in rodents tested in different anxiety models. However, most of these findings are based on social behaviors and, to our knowledge, there is no report concerning the effects of NKP608 in the elevated plus-maze (EPM) and the open field (OF), two classical models of anxiety/emotionality. Moreover, this compound has never been tested in rodent strains that display contrasting levels of anxiety-related behaviors. To investigate the anxiolytic-like effects of NKP608 in Lewis and SHR inbred rats, proposed as a genetic model of anxiety for showing high and low indices of anxiety, respectively. Lewis and SHR rats of both sexes were tested in the EPM and OF tests following acute administration of NKP608 (0.003, 0.03 or 0.3 mg/kg) or chlordiazepoxide (CDZ, 5 mg/kg). Measures of approach/avoidance towards the open arms of the EPM and the central area of the OF were used as indices of anxiety. All doses of NKP608 produced anxiolytic-like effects, similar to those of CDZ, in SHR males tested in the OF but not in the EPM. Conversely, this compound had a partial anxiolytic effect in LEW males (and, to a lower degree, in SHR females) in the EPM, but not in the OF. LEW females were unaffected following all pharmacological treatments. These findings indicate that the anxiety-related effects of NKP608 are strain-, sex- and test-dependent. Moreover, the present data confirm and extend the therapeutic potential of NK1 receptor antagonists for the treatment of anxiety.


Implications of land use/land cover dynamics on urban water quality: Case of Addis Ababa city, Ethiopia.
Water resources are often at the center of urban development but, as the city expands, the environmental pressure on its water resources increases. Therefore, in this study, we looked into how various land uses and changes in land cover affect the water quality in Addis Ababa, Ethiopia. Land use and land cover change maps were generated from 1991 to 2021 at intervals of five years. On the basis of the weighted arithmetic water quality index approach, the water quality for the same years was likewise divided into five classes. The relationship between land use/land cover dynamics and water quality was then evaluated using correlations, multiple linear regressions, and principal component analysis. According to the computed water quality index, the water quality decreased from 65.34 in 1991 to 246.76 in 2021. The built-up area showed an increase of over 338%, whereas the amount of water decreased by over 61%. While barren land exhibited a negative correlation with nitrates, ammonia loadings, total alkalinity, and total hardness of the water, agriculture and built-up areas positively correlated with water quality parameters such as nutrient loading, turbidity, total alkalinity, and total hardness. A principal component analysis revealed that built up areas and changes in vegetated areas have the biggest impact on water quality. These findings suggest that land use and land cover modifications are involved in the deterioration of water quality around the city. This study will offer information that might help reduce the dangers to aquatic life in urbanized environments.


Culture of rat cerebral oligodendrocytes in a serum-free, chemically defined medium.
Oligodendrocytes were isolated from the cerebra of young rats (5-10 days old) by trypsinization of the tissue followed by cell separation on Percoll gradients. The isolation was carried out in physiological, isotonic media. The cell yield was 2-4 X 10(6) cells per brain; the plating efficiency was greater than or equal to 70%. Isolated cells were seeded on poly-L-lysine-coated culture dishes and maintained in a serum-free, chemically defined medium for at least 30 days. After 10 days in culture 67 +/- 10% of the surviving cells were oligodendrocytes, as judged by immunocytochemical and morphological criteria, whereas most of the other cells reacted positively with antiserum against glial fibrillary acidic protein. The expression of typical oligodendrocyte markers (2':3'-cyclic-nucleotide 3'-phosphodiesterase, galactocerebrosides and myelin basic protein) was greatly enhanced under these serum-free conditions as compared with cultures in serum-containing medium. The antigenic markers (galactocerebrosides, myelin basic protein) were absent in the freshly isolated cells but could be detected after 3 days in culture by immunocytochemistry. The activity of 2':3'-cyclic-nucleotide 3'-phosphodiesterase increased from 75 nmol min-1 mg-1 protein on day 4 to 400 nmol min-1 mg-1 protein on day 14 in culture.


Schistosomes with wings: how host phylogeny and ecology shape the global distribution of Trichobilharzia querquedulae (Schistosomatidae).
Migratory waterfowl play an important role in the maintenance and spread of zoonotic diseases worldwide. An example is cercarial dermatitis, caused when larval stages of schistosomes that normally develop in birds penetrate human skin. Members of the genus Trichobilharzia (Schistosomatidae), transmitted mainly by ducks, are considered to be major etiological agents of cercarial dermatitis globally. To better understand the diversity and distribution of Trichobilharzia spp., we surveyed ducks from the United States, eastern Canada, Argentina, South Africa and New Zealand. To aid in species identification of the Trichobilharzia worms recovered, regions of the Cox1, ND4 and ITS1 were sequenced. Furthermore, we provide molecular phylogenetic evidence for the cosmopolitan distribution and trans-hemispheric gene flow for one species, Trichobilharzia querquedulae, previously thought to be restricted to North America. These new samples from endemic non-migratory duck species indicate that T. querquedulae transmission occurs within each of the regions we sampled and that it is specific to the blue-winged+silver teal duck clade. Prevalence within this host group is >95% across the known range of T. querquedulae, indicating that transmission is common. Genetic divergence is evenly distributed among continents, and no phylogenetic structure associated with geography was observed. The results provide strong support for the global distribution and transmission of T. querquedulae and represent, to our knowledge, the first report of a cosmopolitan schistosome confirmed by genetic data. These data are the first known to support trans-hemispheric genetic exchange in a species responsible for causing cercarial dermatitis, indicating that the epidemiology of this group of poorly known zoonotic parasites is more complex than previously expected.


Epidemiologic analysis of the clinical features of Japanese patients with polymyositis and dermatomyositis.
This study aimed to investigate the clinical characteristics of polymyositis/dermatomyositis (PM/DM) in Japan by analyzing data from the nationwide registration system. The data of the registration system in 2009 were analyzed to investigate patient numbers, sex, clinical symptoms, therapies, complications, and prognosis of PM/DM. The total number of PM/DM cases was approximately 17,000, and the female/male sex ratio was 2.7:1. Almost all patients improved as a result of therapy, but many suffered from sequelae such as muscle weakness. The results characterize significant aspects of Japanese PM/DM patients. However, a further prospective survey is required to clarify the true epidemiology and natural history of PM/DM.


Cost-effectiveness analysis of guidelines for antihypertensive care in Finland.
Hypertension is one of the major causes of disease burden affecting the Finnish population. Over the last decade, evidence-based care has emerged to complement other approaches to antihypertensive care, often without health economic assessment of its costs and effects. This study looks at the extent to which changes proposed by the 2002 Finnish evidence-based Current Care Guidelines concerning the prevention, diagnosis, and treatment of hypertension (the ACCG scenario) can be considered cost-effective when compared to modelled prior clinical practice (the PCP scenario). A decision analytic model compares the ACCG and PCP scenarios using information synthesised from a set of national registers covering prescription drug reimbursements, morbidity, and mortality with data from two national surveys concerning health and functional capacity. Statistical methods are used to estimate model parameters from Finnish data. We model the potential impact of the different treatment strategies under the ACCG and PCP scenarios, such as lifestyle counselling and drug therapy, for subgroups stratified by age, gender, and blood pressure. The model provides estimates of the differences in major health-related outcomes in the form of life-years and costs as calculated from a 'public health care system' perspective. Cost-effectiveness analysis results are presented for subgroups and for the target population as a whole. The impact of the use of the ACCG scenario in subgroups (aged 40-80) without concomitant cardiovascular and related diseases is mainly positive. Generally, costs and life-years decrease in unison in the lowest blood pressure group, while in the highest blood pressure group costs and life-years increase together and in the other groups the ACCG scenario is less expensive and produces more life-years. When the costs and effects for subgroups are combined using standard decision analytic aggregation methods, the ACCG scenario is cost-saving and more effective. The ACCG scenario is likely to reduce costs and increase life-years compared to the PCP scenario in many subgroups. If the estimated trade-offs between the subgroups in terms of outcomes and costs are acceptable to decision-makers, then widespread implementation of the ACCG scenario is expected to reduce overall costs and be accompanied by positive outcomes overall.


Evaluation of brain SERT occupancy by resveratrol against MDMA-induced neurobiological and behavioral changes in rats: A 4-[¹⁸F]-ADAM/small-animal PET study.
The misuse of 3,4-methylenedioxymethamphetamine (MDMA) has drawn a growing concern worldwide for its psychophysiological impacts on humans. MDMA abusers are often accompanied by long-term serotonergic neurotoxicity, which is associated with reduced density of cerebral serotonin transporters (SERT) and depressive disorders. Resveratrol (RSV) is a natural polyphenolic phytoalexin that has been known for its antidepressant and neuroprotective effects. However, biological targets of RSV as well as its neuroprotective effects against MDMA remained largely unknown. In this study, we examined binding potency of RSV and MDMA to SERT using small-animal positron emission tomography (PET) with the SERT radioligand, N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) and investigated the protection of RSV against the acute and long-term adverse effects of MDMA. We found that RSV exhibit binding potentials to SERT in vivo in a dose-dependent manner with variation among brain regions. When the MDMA-treated rats (10mg/kg, s.c.) were co-injected with RSV (20mg/kg, i.p.) twice daily for 4 consecutive days, MDMA-induced acute elevation in plasma corticosterone was significantly reduced. Further, 4-[(18)F]-ADAM PET imaging revealed that RSV protected against the MDMA-induced decrease in SERT availability in the midbrain and the thalamus 2 weeks following the co-treatment. The PET data were comparable to the observation from the forced swim test that RSV sufficiently ameliorated the depressive-like behaviors of the MDMA-treated rats. Together, these findings suggest that RSV is a potential antidepressant and may confer protection against neurobiological and behavioral changes induced by MDMA.


Digital artery flaps for closure of soft tissue defects of the forefoot.
Reconstruction of recalcitrant soft tissue defects in the weightbearing surface of the forefoot can be achieved by using a neurovascular island flap. Island flaps, based on a pedicle from either the proper digital artery or the common digital artery, were used to provide supple and durable coverage. A retrospective analysis was performed on 12 patients who underwent a total of 15 digital artery flaps. There were 7 patients with neuropathic ulcers, 7 with a dysfunctional scar, and 1 with an ischemic ulcer after lower-extremity bypass. There was a failure rate of 13%; 2 flaps fully necrosed, necessitating a revisional digital artery flap. Minor complications were reported in 73% of cases; average time to complete healing was 71 days. All healed flaps have remained viable and durable at an average follow-up of 22.5 months from the date of surgery (range, 3 to 61 months).


A new anastomotic leakage model in circular double stapled colorectal anastomosis after low anterior rectum resection in pigs.
A high incidence of anastomotic leakage (37.5%) is reported after low anterior rectal resection (LAR) and circular double-stapled anastomosis without protective ileostoma. Since the pathomechanism of anastomosis leakage is still unclear, a suitable animal model would be most desirable. The objective was to assess the incidence of clinically apparent and inapparent leakage after LAR in pigs (n = 20). Endpoints were radiological, clinical, macroscopic, and histologic proof of anastomotic leakage on the 9th postoperative day. Integrity of anastomosis was assessed by double-contrast barium examination on 9th postoperative day. Animals were sacrificed and anastomoses were resected for histopathological investigation. In case of earlier clinical apparent anastomotic leakage, radiologic double-contrast barium was performed immediately. LAR with a circular double-stapled anastomosis without protective ileostoma was performed in 20 pigs (m:f = 8:12). Length of resection was 10-20 cm, anastomosis was performed 7 cm ab ano. Five animals (25%) developed clinical apparent anastomotic leakage (no appetite, fever, inactivity, tachypnea, discomfort, pain) between the 6th (n = 1) and 9th (n = 4) postoperative day, proven by double-contrast barium radiographs. Additionally in 1 animal clinical inapparent anastomotic insufficiency was observed radiologically. Total rate of leakage was 30% (n = 6). These results were confirmed by leucocytosis, low potassium levels, in two cases high ALT and AST and local peritonitis in all cases. Including one additional case of clinical inapparent leakage, total rate of anastomotic leakage was 30% (6/20). Thus we managed to establish a new experimental model of anastomotic leakage after low rectal resection comparable to the human situation.


The Potential Protective Role of GS-441524, a Metabolite of the Prodrug Remdesivir, in Vaccine Breakthrough SARS-CoV-2 Infections.
Cases of vaccine breakthrough, especially in variants of concern (VOCs) infections, are emerging in coronavirus disease (COVID-19). Due to mutations of structural proteins (SPs) (e.g., Spike proteins), increased transmissibility and risk of escaping from vaccine-induced immunity have been reported amongst the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Remdesivir was the first to be granted emergency use authorization but showed little impact on survival in patients with severe COVID-19. Remdesivir is a prodrug of the nucleoside analogue GS-441524 which is converted into the active nucleotide triphosphate to disrupt viral genome of the conserved non-structural proteins (NSPs) and thus block viral replication. GS-441524 exerts a number of pharmacological advantages over Remdesivir: (1) it needs fewer conversions for bioactivation to nucleotide triphosphate; (2) it requires only nucleoside kinase, while Remdesivir requires several hepato-renal enzymes, for bioactivation; (3) it is a smaller molecule and has a potency for aerosol and oral administration; (4) it is less toxic allowing higher pulmonary concentrations; (5) it is easier to be synthesized. The current article will focus on the discussion of interactions between GS-441524 and NSPs of VOCs to suggest potential application of GS-441524 in breakthrough SARS-CoV-2 infections. The online version contains supplementary material available at 10.1007/s44231-022-00021-4.


[The National Reference Centres and Reference Laboratories. Importance and tasks].
Since 1995, the German Federal Ministry for Health and Social Security funds National Reference Centres (NRC) for the laboratory surveillance of important pathogens and syndromes. Which pathogens or syndromes are selected to be covered by a NRC depends on their epidemiological relevance, the special diagnostic tools, problems with antimicrobial resistance and necessary infection control measures. Currently, there are 15 NRC, which are appointed for a period of 3 years (currently from January 2005 through December 2007). Towards the end of their appointment all NRC are evaluated by a group of specialists. The assessment of their achievements is guided by a catalogue of tasks for the NRC. In addition to the NRC, a total of 50 laboratories are appointed which provide specialist expertise for additional pathogens in order to have a broad range of pathogens for which specialist laboratories are available. Their predominant task is to give advice and support for special diagnostic problems. Both NRC and the specialist laboratories are important parts of the network for infectious disease epidemiology.


Cluster-Randomized Comparative Effectiveness Trial of Physician-Directed Clinical Decision Support Versus Patient-Directed Education to Promote Appropriate Use of Opioids for Chronic Pain.
We compared the effectiveness of physician-directed clinical decision support (CDS) administered via electronic health record versus patient-directed education to promote the appropriate use of opioids by conducting a cluster-randomized trial involving 82 primary care physicians and 951 of their patients with chronic pain. Primary outcomes were satisfaction with patient-physician communication consumer assessment of health care providers and system clinician and group survey (CG-CAHPS) and pain interference patient-reported outcomes measurement information system. Secondary outcomes included physical function (patient-reported outcomes measurement information system), depression (PHQ-9), high-risk opioid prescribing (>90 morphine milligram equivalents per day [≥90 mg morphine equivalent/day]), and co-prescription of opioids and benzodiazepines. We used multi-level regression to compare longitudinal difference-in-difference scores between arms. The odds of achieving the maximum CG-CAHPS score were 2.65 times higher in the patient education versus the CDS arm (P = .044; 95% confidence interval [CI] 1.03-6.80). However, baseline CG-CAHPS scores were dissimilar between arms, making these results challenging to interpret definitively. No difference in pain interference was found between groups (Coef = -0.64, 95% CI -2.66 to 1.38). The patient education arm experienced higher odds of Rx ≥ 90 milligrams morphine equivalent/day (odds ratio = 1.63; P = .010; 95% CI 1.13, 2.36). There were no differences between groups in physical function, depression, or co-prescription of opioids and benzodiazepines. These results suggest that patient-directed education may have the potential to improve satisfaction with patient-physician communication, whereas physician-directed CDS via electronic health records may have greater potential to reduce high-risk opioid dosing. More evidence is needed to ascertain the relative cost-effectiveness between strategies. PERSPECTIVE: This article presents the results of a comparative-effectiveness study of 2 broadly used communication strategies to catalyze dialog between patients and primary care physicians around chronic pain. The results add to the decision-making literature and offer insights about the relative benefits of physician-directed versus patient-directed interventions to promote the appropriate use of opioids.


DeepDrRVO: A GAN-auxiliary two-step masked transformer framework benefits early recognition and differential diagnosis of retinal vascular occlusion from color fundus photographs.
Retinal vascular occlusion (RVO) are common causes of visual impairment. Accurate recognition and differential diagnosis of RVO are unmet medical needs for determining appropriate treatments and health care to properly manage the ocular condition and minimize the damaging effects. To leverage deep learning as a potential solution to detect RVO reliably, we developed a deep learning model on color fundus photographs (CFPs) using a two-step masked SwinTransformer with a Few-Sample Generator (FSG)-auxiliary training framework (called DeepDrRVO) for early and differential RVO diagnosis. The DeepDrRVO was trained on the training set from the in-house cohort and achieved consistently high performance in early recognition and differential diagnosis of RVO in the validation set from the in-house cohort with an accuracy of 86.3%, and other three independent multi-center cohorts with the accuracy of 92.6%, 90.8%, and 100%. Further comparative analysis showed that the proposed DeepDrRVO outperforms conventional state-of-the-art classification models, such as ResNet18, ResNet50d, MobileNetv3, and EfficientNetb1. These results highlight the potential benefits of the deep learning model in automatic early RVO detection and differential diagnosis for improving clinical outcomes and providing insights into diagnosing other ocular diseases with a few-shot learning challenge. The DeepDrRVO is publicly available on https://github.com/ZhouSunLab-Workshops/DeepDrRVO.


TKGWV2: an ancient DNA relatedness pipeline for ultra-low coverage whole genome shotgun data.
Estimation of genetically related individuals is playing an increasingly important role in the ancient DNA field. In recent years, the numbers of sequenced individuals from single sites have been increasing, reflecting a growing interest in understanding the familial and social organisation of ancient populations. Although a few different methods have been specifically developed for ancient DNA, namely to tackle issues such as low-coverage homozygous data, they require a 0.1-1× minimum average genomic coverage per analysed pair of individuals. Here we present an updated version of a method that enables estimates of 1st and 2nd-degrees of relatedness with as little as 0.026× average coverage, or around 18,000 SNPs from 1.3 million aligned reads per sample with average length of 62 bp-four times less data than 0.1× coverage at similar read lengths. By using simulated data to estimate false positive error rates, we further show that a threshold even as low as 0.012×, or around 4000 SNPs from 600,000 reads, will always show 1st-degree relationships as related. Lastly, by applying this method to published data, we are able to identify previously undocumented relationships using individuals that had been excluded from prior kinship analysis due to their very low coverage. This methodological improvement has the potential to enable relatedness estimation on ancient whole genome shotgun data during routine low-coverage screening, and therefore improve project management when decisions need to be made on which individuals are to be further sequenced.


Treatment of unruptured cerebral aneurysms; a multi-center study at Japanese national hospitals.
The treatment and natural course of unruptured cerebral aneurysms were analyzed in 615 patients with 712 unruptured cerebral aneurysms registered from seven Japanese national hospitals and Zurich University hospital. For 209 aneurysms in 181 cases, the natural course of the aneurysms was observed without surgical treatment. During the follow-up period of 3,862 months (321.8 years), 11 of these aneurysms ruptured giving a rupture rate of 3.42%/year. Five of these 11 aneurysms were less than 10 mm in diameter. Seventeen aneurysms of these 209 untreated aneurysms had blebs. Seven of these 17 aneurysms ruptured yielding the high rupture rate of 28.3%/year. The likelihood of unruptured cerebral aneurysms to rupture was not exceedingly low even when the aneurysms were smaller than 10 mm. Since the risk of rupture and morbidity in relation to surgical treatment cannot be predicted by size alone, the morphology, especially the presence of blebs, should be considered when treating unruptured cerebral aneurysms. In 434 patients, 503 cerebral aneurysms were treated surgically either by craniotomy in 472 aneurysms or endovascular coil embolization in 31 aneurysms. Surgical outcome was influenced by the presence of concurrent diseases, patient age, size and location of the aneurysms. Complications after surgical treatment of 128 incidentally found aneurysms were reported in four cases; three cases of hemiparesis and one case showing disturbance of higher brain function, with a morbidity rate of 3.1%. These results suggest that surgical treatment may be acceptable in cases of incidentally found cerebral aneurysms, especially when blebs are present.


Going Skin Deep: Excavating a Diagnosis of Intravascular Large B Cell Lymphoma.
A fever of unknown origin is often pursued diagnostically under the framework of infectious, rheumatologic, and neoplastic causes. When encephalopathy ensues, the differential diagnosis narrows, but can remain elusive, particularly when dealing with rare diseases. We present the case of a patient with fever of unknown origin and intermittent encephalopathy that spanned multiple hospital admissions and ultimately yielded a diagnosis of intravascular large B cell lymphoma complicated by hemophagocytic lymphohistiocytosis. We review the varying presentations of this disease, when to consider this as a diagnosis, and how to most accurately make the diagnosis.


Establishment of a cell line (MCM-B2) from a benign mixed tumour of canine mammary gland.
A cell line was established from a benign mixed tumour of the canine mammary gland. Light microscopy of the cells cultured on plastic dishes revealed monolayer colonies. Cells that grew within the collagen gel matrix formed large three-dimensional colonies with a branching pattern. Immunohistochemically, these cells reacted intensely with anti-vimentin antiserum and mildly with anti-desmin antiserum. Ultrastructural examination revealed a large nucleus, intracytoplasmic organelles and intermediate filaments, which varied among cells. The cells possessed an abnormal chromosome number, an average of 80 per cell. Histologically, the xenografted tumour of cultured cells was similar to anaplastic carcinoma and reacted strongly with anti-vimentin antiserum, mildly with anti-desmin antiserum, and weakly with anti-keratin antiserum. The average chromosome number of cells form the xenografted tumour was the same as that of the original cultured cells. These findings suggest that the cell line might be derived from stem cells or atypical cells, and that it should be useful as model for the study of cell differentiation and proliferation in canine mammary tumours.


Alterations of the oral microbiome in patients treated with the Invisalign system or with fixed appliances.
Although the Invisalign system has been used widely in recent years, the influences of this treatment on the oral microbiome and whether or not this influence is different from that of fixed appliances is still unknown. In this study, we investigated the changes in the oral microbiome in patients treated with the Invisalign system or with fixed appliances. Fifteen subjects were enrolled, comprising 5 fixed appliance patients, 5 Invisalign patient, and 5 healthy controls. Saliva samples were collected, and high-throughput pyrosequencing was performed based on the 16S rRNA gene. Both fixed and Invisalign orthodontic treatments resulted in dysbiosis of the oral microbiome. Firmicutes and TM7 at the phyla level and Neisseria at the genus level displayed statistically significant differences between the 2 orthodontic groups. The effect of these changes with microbiome on oral health was inconsistent. The inferred microbial function of the Invisalign group suggested this group was more predisposed to periodontal diseases. The influence of the Invisalign system on the oral microbiome was no better for oral health compared with fixed appliances. The convenience of maintaining oral hygiene rather than changes in the oral microbiome may be the underlying reason for the performance of the Invisalign system on oral health.


Collection of clinical and epidemiological data for genetic linkage and association studies.
Modern gene-mapping can include linkage studies, which correlate the presence of disease to broad genomic regions in either small or large family units, and association studies, which can narrow the location of a disease-predisposing trait to a single gene using either case-control or family data. This unit provides an overview of key concepts and presents guidelines for collecting diagnostic, epidemiological, and genealogical data from potential study participants. The commentary discusses the use of publicly available data from online resources, methods for evaluating evidence of genetic versus environmental influences in a disease or disease-related endophenotype, and use of e-forms to capture data electronically.


The (pro)renin receptor. A decade of research: what have we learned?
The discovery of a (pro)renin receptor ((P)RR) in 2002 provided a long-sought explanation for tissue renin-angiotensin system (RAS) activity and a function for circulating prorenin, the inactive precursor of renin, in end-organ damage. Binding of renin and prorenin (referred to as (pro)renin) to the (P)RR increases angiotensin I formation and induces intracellular signalling, resulting in the production of profibrotic factors. However, the (pro)renin concentrations required for intracellular signalling in vitro are several orders of magnitude above (patho)physiological plasma levels. Moreover, the phenotype of prorenin-overexpressing animals could be completely attributed to angiotensin generation, possibly even without the need for a receptor. The efficacy of the only available putative (pro)renin receptor blocker handle region peptide remains doubtful, leading to inconclusive results. The fact that, in contrast to other RAS components, (P)RR knock-outs, even tissue-specific, are lethal, points to an important, (pro)renin-independent, function of the (P)RR. Indeed, recent research has highlighted ancillary functions of the (P)RR as an essential accessory protein of the vacuolar-type H(+)-ATPase (V-ATPase), and in this role, it acts as an intermediate in Wnt signalling independent of (pro)renin. In conclusion, (pro)renin-dependent signalling is unlikely in non-(pro)renin synthesizing organs, and the (P)RR role in V-ATPase integrity and Wnt signalling may explain some, if not all of the phenotypes previously associated with (pro)renin-(P)RR interaction.


T2 * relaxation time in Achilles tendinosis and controls and its correlation with clinical score.
To investigate if the T2 * of Achilles tendons can discriminate between chronic Achilles tendinosis and healthy controls; to correlate with clinical score; to evaluate its short-term repeatability; and to estimate minimal detectable change. Twenty patients, with chronic mid-portion Achilles tendinosis, and 10 controls without history of Achilles tendon symptoms, were examined with a 3T MR scanner with a 3D flash ultrashort time to echo sequence with five different echo times. The sequence was run twice to test repeatability. The tendon border was delineated on axial slices at three different levels in the calculated T2 * maps. The clinical severity of Achilles tendinosis was measured by a VISA-A questionnaire. There was a significant difference in mean T2 * between symptomatic and control tendons (P < 0.001). In patients with unilateral symptoms no significant difference in T2 * was found between symptomatic and contralateral asymptomatic tendons (P = 0.19). There was no significant correlation between clinical severity and T2 * (r = -0.28, P = 0.22). The short-term repeatability of T2 * showed a coefficient of variation of 18%, a least significant change of 50%, and the intraclass correlation coefficient had an average consistency of 0.99. T2 * may help to differentiate between chronic Achilles tendinosis and healthy controls but was not associated with the clinical score. However, and notably, the reproducibility of the method was low and the number of patients was small. J. Magn. Reson. Imaging 2016;43:1417-1422.


Improved therapeutic entities derived from known generics as an unexplored source of innovative drug products.
With a New Drug Application (NDA) innovative drug therapies are reaching the market in a specific dosage form for one or more clinically proven indications of which after expiration of the patent or the data exclusivity copies are launched using Abbreviated New Drug Applications (ANDA). Advanced therapies that emerged from launched molecules during their product life-cycle have gained considerable attention as clinical practice provides evidence for additional therapeutic values, patient centric delivery systems show improved therapeutic outcomes or emerging technologies offer efficiency gains in manufacturing or access to emerging markets. The USA and European regulatory framework has set reasonable regulations in place for these "Supergenerics" or "hybrid" applications. While these regulations are relatively recent the pharmaceutical industry is just starting to use this route for their product development and life-cycle management. From a clinical perspective the potential for advanced product development have been demonstrated. Yet, there is still a lag of common understanding between the different stakeholders regarding the development, application process and commercial incentive in developing enhanced therapeutic entities based on existing drug products for the market.


A Rare Cause of Diarrhea in a Kidney Transplant Recipient: Dipylidium caninum.
We report the first case of dipylidiasis in a kidney transplant recipient. Watery diarrhea due to Dipylidium caninum was observed in a male patient who had been undergone kidney transplantation 2 years before. The patient was successfully treated with niclosamide. D. caninum should be considered as an agent of diarrhea in transplant patients.


Improved, Odorless Access to Benzo[1,2-d;4,5-d']- bis[1,3]dithioles and Tert-butyl Arylsulfides via C-S Cross Coupling.
Benzo[1,2-d;4,5-d']bis[1,3]dithioles are important building blocks within a range of functional materials such as fluorescent dyes, conjugated polymers, and stable trityl radicals. Access to these is usually gained via tert-butyl aryl sulfides, the synthesis of which requires the use of highly malodorous tert-butyl thiol and relies on SNAr-chemistry requiring harsh reaction conditions, while giving low yields. In the present work, S-tert-butyl isothiouronium bromide is successfully applied as an odorless surrogate for tert-butyl thiol. The C-S bond formation is carried out under palladium catalysis with the thiolate formed in situ resulting in high yields of tert-butyl aryl sulfides. The subsequent formation of benzo[1,2-d;4,5-d']bis[1,3]dithioles is here achieved with scandium(III)triflate, a less harmful reagent than the usually used Lewis acids, e.g., boron trifluoride or tetrafluoroboric acid. This enables a convenient and environmentally more compliant access to high yields of benzo[1,2-d;4,5-d']bis[1,3]dithioles.


Equivalent circuit of a silicon-lithium p-i-n nuclear radiation detector.
Nuclear radiation detectors are indispensable for research in the field of nuclear radiation, X-ray spectroscopy and other areas. Interest in silicon p-i-n detectors of nuclear radiation is increasing today due to the possibility of their operation under normal conditions. In this paper, an equivalent circuit of a silicon-lithium p-i-n nuclear radiation detector is proposed. The proposed circuit is obtained using the classical Shockley equation for silicon semiconductors and the telegraph equations. The parameters of the equivalent circuit were determined using the multiple regression method. As a result of simulation of the model in the MATLAB Simulink graphical development environment, the amplitude-frequency and phase-frequency characteristics of the proposed model were obtained. Using the Monte Carlo method, the alpha-decay of the uranium isotope [Formula: see text], thorium isotope [Formula: see text] and americium isotope [Formula: see text] the alpha-decay spectrum was obtained. Obtained alpha-decay spectra coincides with the experimental data, presented in previous works of other authors.


Physical Activity, Vitamin D, and Incident Atherosclerotic Cardiovascular Disease in Whites and Blacks: The ARIC Study.
Physical activity (PA) is associated with 25-hydroxyvitamin D [25(OH)D] levels. Both are associated with atherosclerotic cardiovascular disease (ASCVD), but their joint association with ASCVD risk is unknown. To examine the relationship between PA and 25(OH)D, and assess effect modification of 25(OH)D and PA with ASCVD. Cross-sectional and prospective study. Community-dwelling cohort. A total of 10,342 participants free of ASCVD, with moderate- to vigorous-intensity PA assessed (1987 to 1989) and categorized per American Heart Association (AHA) guidelines (recommended, intermediate, or poor). Serum 25(OH)D levels (1990 to 1992) and ASCVD events (i.e., incident myocardial infarction, fatal coronary disease, or stroke) through 2013. Participants had mean age of 54 years, and were 57% women, 21% black, 30% 25(OH)D deficient [<20 ng/mL (<50 nmol/L)], and <40% meeting AHA-recommended PA. PA was linearly associated with 25(OH)D levels in whites. Whites meeting recommended PA were 37% less likely to have 25(OH)D deficiency [relative risk, 0.63 (95% confidence interval [CI], 0.56, 0.71)]; there was no significant association in blacks. Over 19.3 years of follow-up, 1800 incident ASCVD events occurred. Recommended PA was associated with reduced ASCVD risk [hazard ratio [HR], 0.78 (95% CI, 0.65, 0.93) and 0.76 (95% CI, 0.62, 0.93)] among participants with intermediate [20 to <30 ng/mL (50 to <75 nmol/L)] and optimal [≥30 ng/mL (≥75 nmol/L)] 25(OH)D, respectively, but not among those with deficient 25(OH)D (P for interaction = 0.04). PA is linearly associated with higher 25(OH)D levels in whites. PA and 25(OH)D may have synergistic beneficial effects on ASCVD risk.


[Not Available].
Juvenile idiopathic arthritis is a chronic inflammatory disease with uncertain outcome. Patients may suffer from severe joint damage leading to mutilations as well as from extra-articular manifestations. Prognosis is variable and depends in part on the number of affected joints and the occurrence of extra-articular manifestations. Treatment regimes should take this into account. Pharmacomedical treatment strategies include the application of nonsteroidal antirheumatics, corticosteroids, sulfasalazine, and immunosuppressive substances. However, of the latter only methotrexate has been shown in controlled trials to be effective. Other immunosuppressive drugs such as azathioprine, cyclosporine A, and leflunomide have not yet been investigated sufficiently. In addition, there is no scientific basis for the application of gold salts or (hydroxy)chloroquine. New therapeutic biologic agents, notably the tumor necrosis factor inhibitors, have achieved dramatic improvements also in patients with severe, as yet intractable disease. However, until now randomized, placebo-controlled trials have been performed for etanercept only. Dramatic improvement was accompanied by low toxicity. Infections as well as the development of autoimmune diseases have been shown to be the major potential side effects. Long-term toxicity still has to be evaluated. Treatment with other biopharmaceuticals such as infliximab, IL-1Ra, anti-IL-6 receptor antibodies, and further cytokine antagonists remains experimental.


Cervical screening in high-income countries: the need for quality assurance, adjunct biomarkers and rational adaptation to HPV vaccination.
We here discuss human papillomavirus (HPV)-based screening avenues to achieve elimination of cervical cancer as a public health problem in high-income country (HIC) settings, covering both the most recent data on the performance of HPV testing, as well as the currently most robust triage methods that are known. We also provide an outlook to several other promising, yet not fully established, options for triage that have been proposed, including methylation, dual staining, machine learning, and artificial intelligence. Finally, we discuss the key issue of how to adapt screening in the presence of programmatic HPV vaccination, and how this combination can best be leveraged for comprehensive cancer control. We conclude that, for the HIC setting, evidence-based and effective cervical screening methods are readily available, but whichever method or platform is chosen, we would propose that recurring audits of performance and population attendance remain common denominators for maintaining successful disease prevention.


Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor.
Parkinson's disease (PD) and essential tremor (ET) are two common adult-onset tremor disorders in which prevalence increases with age. PD is a neurodegenerative condition with progressive disability. In ET, neurodegeneration is not an established etiology. We sought to determine whether an underlying metabolic pattern may differentiate ET from PD. Circulating metabolites in plasma and cerebrospinal fluid (CSF) were analyzed using gas chromatography-mass spectroscopy. There were several disrupted pathways in PD compared to ET plasma including glycolysis, tyrosine, phenylalanine, tyrosine biosynthesis, purine and glutathione metabolism. Elevated α-synuclein levels in plasma and CSF distinguished PD from ET. The perturbed metabolic state in PD was associated with imbalance in the pentose phosphate pathway, deficits in energy production, and change in NADPH, NADH and nicotinamide phosphoribosyltransferase levels. This work demonstrates significant metabolic differences in plasma and CSF of PD and ET patients.


A novel bio-inspired conductive, biocompatible, and adhesive terpolymer based on polyaniline, polydopamine, and polylactide as scaffolding biomaterial for tissue engineering application.
A novel electrically conductive nanofibrous scaffold based on polyaniline-co-(polydopamine-grafted-poly(d,l-lactide)) [PANI-co-(PDA-g-PLA)] was fabricated using electrospinning technique and its physicochemical as well as biological characteristics toward bone tissue engineering (TE) were investigated extensively. In detail, PANI-co-PDA was synthesized via a one-step chemical oxidization approach. Then, d,l-lactaide monomer was grafted onto PDA segment using a ring opening polymerization (ROP) to afford PANI-co-(PDA-g-PLA) terpolymer. The successful synthesis of PANI-co-(PDA-g-PLA) terpolymer was confirmed using FTIR spectroscopy as well as TGA analysis. Finally, a solution of the synthesized terpolymer was electrospun to fabricate a conductive nanofibrous scaffold. Some physicochemical features such as mechanical, conductivity, electroactivity, hydrophobicity, and morphology as well as biological characteristics including biocompatibility, biodegradability, as well as enhancing the cells adhesion and proliferation were investigated. According to the above-mentioned experimental results, the fabricated electrospun nanofibers can be considered as a potential scaffold for TE application, mainly due to its proper physicochemical and biological properties.


DNA content distribution of in vivo and in vitro lines of Lewis lung carcinoma.
The kinetic features of Lewis lung carcinoma (3LL) and of two in vitro and two in vivo derivative lines were studied by flow cytometry. The in vitro lines C108 and BC215 show the same tetraploid DNA content and a very similar cell cycle structure, characterized by a prevalent S fraction. Also, the in vivo lines, the original 3LL and M1087, show a tetraploid DNA content, while the BM21548 is characterized by a hyperdiploid DNA mode and a broader distribution of DNA values. No difference in the modal DNA value is found between each primary tumor and the corresponding lung metastases for all the in vivo lines. In addition, an increase in the G1 component corresponding to a decrease in the S fraction is observed during the tumor growth. These kinetic features were related to some malignant properties of 3LL lines, such as growth pattern and metastatic potential. Our findings indicate that a direct correlation is not always possible to establish.


Catalytic properties, localization, and in vivo role of Px IV, a novel tryparedoxin peroxidase of Trypanosoma brucei.
Px IV is a distant relative of the known glutathione peroxidase-type enzymes of African trypanosomes. Immunofluorescence microscopy of bloodstream cells expressing C-terminally Myc6-tagged Px IV revealed a mitochondrial localization. Recombinant Px IV possesses very low activity as glutathione peroxidase but catalyzes the trypanothione/tryparedoxin-dependent reduction of hydrogen peroxide and, even more efficiently, of arachidonic acid hydroperoxide. Neither overexpression in bloodstream cells nor the deletion of both alleles in bloodstream or procyclic parasites affected the in vitro proliferation. Trypanosoma brucei Px IV shares 58% of all residues with TcGPXII. The orthologous enzymes have in common their substrate preference for fatty acid hydroperoxides. However, the T. cruzi protein has been reported to be localized in the endoplasmic reticulum and to be specific for glutathione as reducing agent. Taken together, our data show that Px IV is a low abundant tryparedoxin peroxidase of T. brucei that is not essential, at least under culture conditions.


Abnormal orientation selectivity in both eyes of strabismic amblyopes.
In normal observers preadaptation to a parallel grating increases the contrast threshold for a line whereas a perpendicular grating has no effect. Such orientation selectivity was not found in the amblyopic eye of two out of five squinters. Only a weak after-effect produced with a grating parallel to the line was obtained in the good eye of four of the amblyopes while all of them show an abnormal threshold reduction following adaptation to a perpendicular grating. This suggests a relationship between abnormal binocular interaction during visual development and the organization of orientational mechanisms but does not explain the loss of visual acuity in amblyopia.


Conformational analysis of cyclolinopeptide A, a cyclic nonapeptide: nuclear Overhauser effect and energy minimization studies.
The conformation of cyclolinopeptide A [cyclo(Pro-Pro-Phe-Phe-Leu-Ile-Ile-Leu-Val)], a naturally occurring cyclic nonapeptide has been investigated in dimethylsulfoxide solution by 270 MHz 1H-nmr. A complete assignment of all C alpha H and NH resonances has been accomplished using two-dimensional correlated spectroscopy and nuclear Overhauser effects (NOEs). Analysis of interresidue NOEs and JHNC alpha H values permit construction of a molecular model for the cyclic peptide backbone. The crude model derived from nmr has been used as a starting point for energy minimization, which yields a refined structure largely compatible with nmr observations. The major features of the conformation of cyclolinopeptide A are a Type VI beta-turn centered at Pro(1)-Pro(2), with a cis peptide bond between these residues and a gamma-turn (C7 structure) centered at Ile(6). Two intramolecular hydrogen bonds Val(9) CO--Phe(3)NH (4----1) and Leu(5) CO--Ile(7)NH (3----1) are observed in the low-energy conformation. The limited solvent accessibility observed for the Val(9) and Leu(5) NH groups in the nmr studies are rationalized in terms of steric shielding.


Surgical outcomes in elective sigmoid resection for diverticulitis stratified according to indication: a propensity-score matched cohort study with 903 patients.
Weighing the perioperative risk of elective sigmoidectomy is done regardless of the specific diverticulitis classification. The aim of this study is to evaluate surgical outcomes according to the classification grade and the indication. All patients who underwent elective colonic resection for diverticulitis during the ten-year study period were included. They were divided into two groups: relative surgery indication (RSI) and absolute surgery indication (ASI). RSI included microabscess and recurrent uncomplicated disease. ASI included macroabscess and recurrent complicated disease. Propensity score-matching (PSM, 1:1) was performed. 585 patients fulfilled criteria for RSI and 318 patients fulfilled criteria for ASI. In the univariate analysis, RSI patients were younger (62 vs. 67.7 years, p < 0.001), had a higher physical status (ASA score 1 or 2 in 80.7% vs. 60.8%, p < 0.001), were less immunosuppressed (3.4% vs. 6.9%, p = 0.021) and suffered less often from coronary heart disease (3.8% vs. 7.2%, p = 0.025). After PSM, 318 RSI vs. 318 ASI patients were selected; baseline characteristics results were comparable. The proportion of planned laparoscopic resection was 93% in RSI versus 75% in ASI (p < 0.001), and the conversion rate to open surgery for laparoscopic resection was 5.0% and 13.8% in RSI versus ASI, respectively (p < 0.001). Major morbidity (Clavien/Dindo ≥ IIIb) occurred less frequently in RSI (3.77% vs. 10%, p = 0.003). A defunctioning stoma was formed in 0.9% and 11.0% in RSI vs ASI, respectively (p < 0.001). The lower risk for postoperative morbidity, the higher chance for a laparoscopic resection and the decreased rate of stoma formation are attributed to patients with recurrent uncomplicated diverticulitis or diverticulitis including a microabscess as compared to patients with complicated diverticulitis or diverticulitis and a macroabscess, and this applies even after PSM.


[Effect of emotional-algesic stress on the hormonal function of thyroid and parathyroid glands].
Experiments on 215 Wistar rats have revealed that the state of the endured stress is an essential factor inducing disturbance in functioning of the hypothalamus-adenohypophysis-thyroid gland system accompanied by disturbance in regulation of the thyrotropin and triiodothyronine formation under conditions of myocardium necrosis development.


The MCH neuron population as a model for the development and evolution of the lateral and dorsal hypothalamus.
The LHA contains neurons producing melanin-concentrating hormone (MCH) or hypocretin (Hcrt) that have emerged as being more conspicuous and representative of the posterior LHA. In this review, we focus on MCH neurons and show that they have unique qualities. Their distribution is conserved in the posterior hypothalamus of all vertebrates and their ontogenetic differentiation is very precocious in the rodent embryo. In mammals, interspecific differences in their medio-lateral distribution suggest that the LHA differentiation may follow species specific strategies. These characteristics make a very valuable tool of MCH neurons to study the development as well as the phylogenetical origin and differentiation of the LHA.


[Cerebral infarction after pituitary apoplexy: Description of a case and review of the literature].
Pituitary apoplexy is usually the result of hemorrhagic infarction in a pituitary adenoma. The clinical presentation varies widely and includes asymptomatic cases, classical pituitary apoplexy and even sudden death. Cerebral ischemia due to pituitary apoplexy is very rare. It may be caused by vasospasm or direct compression of cerebral vessels by the tumor. We report a case of pituitary apoplexy associated with cerebral infarction and discuss the relationship between the two events.


Constrained dynamics via the Zeno effect in quantum simulation: implementing non-Abelian lattice gauge theories with cold atoms.
We show how engineered classical noise can be used to generate constrained Hamiltonian dynamics in atomic quantum simulators of many-body systems, taking advantage of the continuous Zeno effect. After discussing the general theoretical framework, we focus on applications in the context of lattice gauge theories, where imposing exotic, quasilocal constraints is usually challenging. We demonstrate the effectiveness of the scheme for both Abelian and non-Abelian gauge theories, and discuss how engineering dissipative constraints substitutes complicated, nonlocal interaction patterns by global coupling to laser fields.


An efficient synthesis of indolo[3,2-a]carbazoles via the novel acid catalyzed reaction of indoles and diaryl-1,2-diones.
A mild and efficient one pot method for the synthesis of indolo[3,2-a]carbazole derivatives by the para-toluenesulfonic acid catalyzed condensation of indole with acyclic 1,2-diones is described. With cyclobutene-1,2-diones the reaction afforded indole substituted carbazole derivatives in good yield.


Associations of the G1961E and D2177N variants in ABCA4 and the risk of age-related macular degeneration.
The aim of this study was to identify the relationship between G1961E and D2177N variants in the ABCA4 gene with AMD susceptibility. All eligible studies published up to October 2014 were obtained from MEDLINE, EMBASE, and ISI Web of Science. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate the strength of this association. Twenty-four studies enrolling 4580 AMD cases and 5180 controls were identified. Both G1961E (OR = 3.22, 95% CI: 1.74-5.95) and D2177N (OR = 2.36, 95% CI: 1.41-3.93) variations showed significant associations with increased risk of AMD. In addition, a more significant relationship in the D2177N mutation with increased risk for AMD was found in Americans (OR = 4.31, 95% CI: 1.90-9.73), while no association was demonstrated in Europeans. For Asians, no carriers of the risk factor A allele in either variant were detected in any of AMD patients and control subjects. Significant evidence was found for a relationship between the G1961E and D2177N variants in ABCA4 with increased susceptibility to AMD, specifically for Americans. However, large-scale studies are still required to further validate these findings in different ethnicities.