A novel spectral analysis method for distinguishing heavy metal stress of maize due to copper and lead: RDA and EMD-PSD.
Monitoring heavy metal stress in crops via hyperspectral remote sensing technology is an effective way. A new approach, namely the ratio difference of autocorrelation function first derivative (RDA), is proposed to extract characteristic regions of maize leaves spectra for the initially identification on contaminated category of copper (Cu) and lead (Pb). Simultaneously, empirical mode decomposition (EMD) and power spectral density (PSD) are integrated to construct EMD-PSD to visually discrimination on Cu and Pb stress from frequency domain perspective. In our work, pot experiment contaminated by Cu and Pb were designed and carried out, and corresponding chemical data, chlorophyll and spectra of maize leaves were collected. Based on acquired spectra, RDA is used to obtain indicators and characteristic intervals of spectra, and then EMD-PSD is applied to obtain intrinsic mode functions (IMFs) from spectra and PSD maps. Through experimental analysis, the following conclusions are drawn: 1) the red edge and red shoulder region of spectra can be used as candidate on indicator to find the characteristic regions of spectra, and integrated intersection spectral intervals are considerable to distinguish Cu and Pb; 2) PSD maps extracted by EMD-PSD significantly can discriminate stress of Cu and Pb with three-dimensional visualization. This study takes the combination of spectral domain and frequency domain as the exploration point, the stress of Cu and Pb was distinguished by mutual verification based on spectra (group I and group II and 2014 experiment). In summary, the proposed method can identify the weak differences of spectra and distinguish the stress of Cu and Pb qualitatively, which provides a new perspective for the identification of heavy metal stress categories.


A comparison of treadmill training and overground walking in ambulant children with cerebral palsy: randomized controlled clinical trial.
Compare the effects of treadmill training and training with overground walking (both without partial weight support) on motor skills in children with cerebral palsy. Randomized controlled clinical trial. Physical therapy clinics. Thirty-six children with cerebral palsy (levels I-III of the Gross Motor Functional Classification System) randomly divided into two intervention groups. Experimental group (17 children) submitted to treadmill training without partial weight support. Overground walking group (18 children) submitted to gait training on a fixed surface (ground). Training was performed for seven consecutive weeks (two sessions per week), with four subsequent weeks of follow-up. Both groups demonstrated improvements on the 6-minute walk test (experimental group from 227.4 SD 49.4 to 377.2 SD 93.0; overground walking group from 222.6 SD 42.6 to 268.0 SD 45.0), timed up-and-go test (experimental group from 14.3 SD 2.9 to 7.8 SD 2.2; overground walking group from 12.8 SD 2.2 to 10.5 SD 2.5), Pediatric Evaluation Disability Inventory (experimental group from 128.0 SD 19.9 to 139.0 SD 18.4; overground walking group from 120.8 SD 19.0 to 125.8 SD 12.2), Gross Motor Function Measure-88 (experimental group from 81.6 SD 8.7 to 93.0 SD 5.7; overground walking group from 77.3 SD 7.0 to 80.8 SD 7.2), Berg Balance Scale (experimental group from 34.9 SD 8.5 to 46.7 SD 7.6; overground walking group from 31.9 SD 7.0 to 35.7 SD 6.8) after treatment. The experimental group demonstrated greater improvements than the overground walking group both after treatment and during follow up (p < 0.05). Treadmill training proved more effective than training with overground walking regarding functional mobility, functional performance, gross motor function and functional balance in children with cerebral palsy.


Clinical pharmacokinetics of losartan.
Losartan is the first orally available angiotensin-receptor antagonist without agonist properties. Following oral administration, losartan is rapidly absorbed, reaching maximum concentrations 1-2 hours post-administration. After oral administration approximately 14% of a losartan dose is converted to the pharmacologically active E 3174 metabolite. E 3174 is 10- to 40-fold more potent than its parent compound and its estimated terminal half-life ranges from 6 to 9 hours. The pharmacokinetics of losartan and E 3174 are linear, dose-proportional and do not substantially change with repetitive administration. The recommended dosage of losartan 50 mg/day can be administered without regard to food. There are no clinically significant effects of age, sex or race on the pharmacokinetics of losartan, and no dosage adjustment is necessary in patients with mild hepatic impairment or various degrees of renal insufficiency. Losartan, or its E 3174 metabolite, is not removed during haemodialysis. The major metabolic pathway for losartan is by the cytochrome P450 (CYP) 3A4, 2C9 and 2C10 isoenzymes. Overall, losartan has a favorable drug-drug interaction profile, as evidenced by the lack of clinically relevant interactions between this drug and a range of inhibitors and stimulators of the CYP450 system. Losartan does not have a drug-drug interaction with hydrochlorothiazide, warfarin or digoxin. Losartan should be avoided in pregnancy, as is the case with all other angiotensin-receptor antagonists. When given in the second and third trimester of pregnancy, losartan is often associated with serious fetal toxicity. Losartan is a competitive antagonist that causes a parallel rightward shift of the concentration-contractile response curve to angiotensin-II, while E 3174 is a noncompetitive "insurmountable" antagonist of angiotensin-II. The maximum recommended daily dose of losartan is 100mg, which can be given as a once-daily dose or by splitting the same total daily dose into two doses. Losartan reduces blood pressure comparably to other angiotensin-receptor antagonists. Losartan has been extensively studied relative to end-organ protection, with studies having been conducted in diabetic nephropathy, heart failure, post-myocardial infarction and hypertensive patients with left ventricular hypertrophy. The results of these studies have been sufficiently positive to support a more widespread use of angiotensin-receptor antagonists in the setting of various end-organ diseases. Losartan, like other angiotensin-receptor antagonists, is devoid of significant adverse effects.


First study on seroepidemiology and isolation of Toxoplasma gondii in free-range chickens in the semi-arid region of Paraíba state, Brazil.
The aim of this study was to investigate the seroprevalence and isolation of Toxoplasma gondii in free-range chickens in the state of Paraíba, northeastern Brazil. For this, blood samples were collected from 483 chickens in five municipalities in the state of Paraíba. The indirect immunofluorescence assay for anti-T. gondii antibodies was performed. The seropositive birds were slaughtered, and their brains and hearts were collected in order to perform a bioassay in mice. An epidemiological questionnaire was applied on the smallholdings visited, and univariable and multivariable logistic regressions were used to evaluate risk factors. The prevalence of chickens seropositive for T. gondii was found to be 31.5 % (152/483), and 86.1 % (56/65) of the smallholdings were positive. Among the 71 chickens subjected to bioassaying in mice, isolates of T. gondii were obtained from 33 (46.5 %). The isolates were named TgCkBrPB1 to 33. It was observed that the higher the chickens' antibody titer was, the greater the chance of isolating the parasite also was. Sixteen of the 33 isolates (48.5 %) were lethal for all the mice inoculated until 30 days post-inoculation. The risk factors for infection with T. gondii among these free-range chickens were extensive and semi-extensive rearing systems, smallholdings located in urban areas, and presence of cats. The results indicate that the prevalence of T. gondii among chickens in the state of Paraíba is high. Many parasites remained viable in the tissues of the birds studied, and presence of the protozoan was directly related to the management of these birds.


Characteristics of the muscle involvement along the disease progression in a large cohort of oculopharyngodistal myopathy compared to oculopharyngeal muscular dystrophy.
Oculopharyngodistal myopathy (OPDM) is an autosomal dominant myopathy clinically characterized by distal muscle weakness. Even though the identification of four causative genes, LRP12, GIPC1, NOTCH2NLC and RILPL1, it is unclear whether the myopathy progressed similarly among OPDM subtypes. We aimed to establish diagnostic clues in muscle imaging of OPDM in comparison with clinicopathologically similar oculopharyngeal muscular dystrophy (OPMD). Axial muscle CT and/or T1-weighted MRI data from 54 genetically confirmed patients with OPDM (OPDM_LRP12; n = 43, OPDM_GIPC1; n = 6, OPDM_NOTCH2NLC; n = 5) and 57 with OPMD were evaluated. We scored the degree of fat infiltration in each muscle by modified Mercuri score and performed hierarchical clustering analyses to classify the patients and infer the pattern of involvement on progression. All OPDM subtypes showed a similar pattern of distribution in the affected muscles; soleus and medial gastrocnemius involved in the early stage, followed by tibialis anterior and extensor digitorum longus. For differentiating OPDM and OPMD, severely affected gluteus medius/minimus and adductor magnus was indicative of OPMD. We identified a diagnostic muscle involvement pattern in OPDM reflecting its natural history. The results of this study will help in the appropriate intervention based on the diagnosis of OPDM, including its stage.


Trace metal contamination status in soils of the abandoned gold mining district of Bindiba (East Cameroon): Pollution indices assessment, multivariate analysis and; geostatistical approach.
In this study, contamination by trace metals (TMs) such as Cr, Ni, Cu, As, Pb and Sb in the soils of the Bindiba mining district was assessed. This study aims to reveal the current status of the soil quality of the abandoned gold mining district of Bindiba and provide a scientific basis for its future remediation and overall management. 89 soil samples were systematically collected and characterized in order to determine the concentration of TMs (Cr, Ni, Cu, As, Pb and Sb). To assess the degree of metallic contamination, pollution indices were employed. Both multivariate statistical analysis (MSA) and geostatistical modelling (GM) were used to identify the potential sources of TMs elements and to determine the values of the modified contamination degree (mCd), the Nemerow Pollution Index (NPI) and the potential ecological risk index (RI) at un-sampled points. The results of trace metals (TMEs) characterization showed that the concentration of Cr, Ni, Cu, As, Pb and Sb ranged from 22.15-442.44 mg/kg, 9.25-360.37 mg/kg, 1.28-320.86 mg/kg, 0-46.58 mg/kg, 0-53.27 mg/kg and 0-6.33 mg/kg, respectively. The mean concentration of Cr, Cu and Ni exceeds the continental geochemical background values. The Enrichment Factor (EF) assessment indicates two categories of enrichment: moderately to extremely enrichment for Cr, Ni, and Cu and deficiency to minimal enrichment of Pb, As and Sb. Multivariate statistical analysis shows weak linear correlations between the studied heavy metals and suggests that these metals could not come from the same origins. The geostatistical modelling based on the values of mCd, NI and RI suggests a potential high pollution risk existed in the study area. The mCd, NPI and RI interpolation maps showed that the Northern part of the gold mining district was characterized by a high degree of contamination, heavy pollution, and considerable ecological risk. The dispersion of TMs in soils could mainly be attributed to anthropogenic activities and natural phenomena (chemical weathering or erosion). Appropriate measures should be taken to manage and remediate the TMs pollution in this abandoned gold mining district in order to reduce its negative effects on the environment and health of the local population. The online version contains supplementary material available at 10.1007/s40201-023-00849-y.


Role of MAPK ERK1/2 and p38 in the Regulation of Secretory Functions of Different Populations of Neuroglia in Ethanol-Induced Neurodegeneration.
We studied the participation of ERK1/2 and p38 in secretion of neurotrophic growth factors by various types of neuroglia under conditions of in vitro and in vivo modeled ethanol-induced neurodegeneration. The inhibitory role of these protein kinases in the production of neurotrophins by intact astrocytes and the absence of their participation in the regulation of functions of oligodendrocytes and microglial cells were shown. Under conditions of ethanol neurotoxicity, the role of ERK1/2 and p38 in the production of growth factors by glial elements was significantly changed. Neurodegeneration modeled in vitro led to inversion of the role of both protein kinases in the secretion of neurotrophins by astroglia and inhibition of the cytokine-synthesizing function of oligodendrocytes and microglial cells by ERK1/2 and p38. In mice receiving ethanol per os for a long time (as well as in cells in vitro exposed to ethanol), mitogen-activated kinases stimulated the function of astrocytes and inhibited the production of growth factors by microglial cells. At the same time, chronic alcoholization was accompanied by the appearance of the stimulating role of ERK1/2 and p38 in the implementation of the secretory function by oligodendrocytes.


Burnout Among Otolaryngology Residents in Saudi Arabia: A Multicenter Study.
Determine the prevalence of, and associated risk factors for, burnout among otolaryngologist residents in Saudi Arabia. A cross-section study of multicenter hospitals in Saudi Arabia conducted in March 2013. Registered residents in Saudi Otolaryngology Board Program. The Maslach Burnout Inventory was used to measure burnout status. Questions supplementary to the Maslach Burnout Inventory were also included to identify associated potential risk factors such as demographic data, resident satisfaction, and work conditions. Of the initial 123 questionnaires that were distributed, 85 yielded responses, a rate of 69%. The mean age (standard deviation [SD]) of respondents was 29 (2.3) years. Of those, 67% (57/85) were men and 66% (55/85) were married. Resident levels were delineated: level 2, 19%; level 3, 33%; level 4, 29%; and level 5, 19%. The mean number of on-call days/month (SD) was 7 (2), clinics/week (SD) was 3 (1), sleep hours/day (SD) was 6 (1), and operations/week (SD) was 2 (1). The mean emotional exhaustion (EE) and depersonalization scores were high at 29.5 (SD = 9.6) and 10.7 (SD = 6), respectively. The mean personal accomplishment was low at 32.33 (SD = 6). The mean of all subscales did not differ by sex (EE p = 0.5; depersonalization p = 0.09; personal accomplishment p = 0.4). Mean EE differed by marital status, which was 31.2, 31.3, and 25.6 for married, divorced, and single, respectively, analysis of variance test p = 0.045. Burnout prevalence was found to be high among otolaryngologist residents in Saudi Arabia. The associated variables examined in this study should be addressed to decrease this level of burnout and provide residents with a less stressful work environment.


(Electron) microscopic observations on tissue integration of collagen-immobilized polyurethane.
The foreign body reactions to collagen-immobilized polyurethane (PU-CI) films during subcutaneous implantation in rats were characterized. The underlying concept is that collagen-immobilization will improve the tissue integration. Since the method of collagen-immobilization involves the covalent coupling of collagen to an acrylic acid (AA) based surface graft, both non-modified PU and PU-AA were used as controls. Bare PU has a flat surface, whereas both PU-AA and PU-CI displayed a slightly roughened surface. Implantation showed that PU-CI induced early after implantation a far more intense foreign body reaction than PU and PU-AA. This reaction consisted of increased presence of fibrin, granulocytes and macrophages. Roughening of the surface as with PU-AA induced only a small increase in fibrin formation and cellular migration. At day 5 the reaction to PU-CI had slowed down; giant cell formation now slowly started but was decreased compared to PU and PU-AA. At day 10 capsules around each type of material looked similar, but in contrast to PU. PU-CI films could no longer be dissected from their capsules. Only at week 3 this also occurred with PU, at which time point again similar capsules with the three materials were observed. At week 6, of the three materials PU-CI showed the thinnest capsule with most immediate adherence of connective tissue. These results show that collagen-immobilization of PU increased the early tissue reaction and therefore the tissue integration. The thin capsule observed at 6 weeks may be beneficial in e.g. infectious circumstances, when easy access for immune reactions is needed. This, and the long-term performance of PU-CI will be a matter of future investigations.


Interspecific interactions tested: two species of malarial parasite in a West African lizard.
Plasmodium giganteum and P. agamae, parasites of the rainbow lizard, Agama agama, in West Africa were studied to determine the nature of any interspecific interactions between the two malaria species. The plasmodia are distributed in A. agama throughout the mesic zone of Africa; P. agamae is sometimes found as a solitary malaria species in populations of the lizard, but P. gigateum has not been found alone. In 3170 lizards from Sierra Leone the prevalence of lizard malaria at 22 sites varied considerably (8-90% of lizards were infected), but the ratio of the two species was similar among sites (52-91% P. agamae). Larger lizards were more often infected. Mixed infections occurred 2-5 times more often than expected by chance. Parasite density within individual hosts, or parasitemia, was similar for each species when alone or in mixed infection. Natural infections followed in laboratory lizards stayed at constant levels for as long as 211 days. The two species use different classes of host cells (P. giganteum in immature cells and P. agamae in mature erythrocytes) and may have different periods of peak transmission. Analysis of the data does not support a neutral relationship between P. giganteum and P. agamae, nor ongoing competition for resources or heterologous immunity. The data best support facilitation in which P. agamae alters the host in a way that allows more successful establishment of P. giganteum.


Lymphomas resembling lymphoid leukosis in chickens inoculated with reticuloendotheliosis virus.
Chickens inoculated as embyros or at hatching with the chick syncytial strain of reticuloendotheliosis virus developed a high incidence of lymphoid neoplasms between the 17th and 43rd weeks of age, involving principally the liver and bursa of Fabricius. On the basis of organ distribution, latent period, pathology and surface IgM production, the lymphomas closely resembled those of lymphoid leukosis. One inoculated chicken developed a myxosarcoma. No tumors were observed in uninoculated controls. The tumor-bearing chickens were free of infection with Marek's disease virus and exogenous avian leukosis virus (ALV) of subgroups A, B, C or D. However, the chickens were known to express endogenous ALV genes to varying degrees.


Transanal Endoscopic Microsurgery (TEM): the first endoluminal endoscopic surgery.
The typical concept of endoscopic surgery is the performance of surgical procedures in the two major body cavities, the abdomen and thorax. To perform this, small incisions for the ports are needed to introduce optics and instruments. Typically, the optic and the instruments are introduced from different angles. The access itself is associated with a reduced trauma.


Effect of high hydrostatic pressure on the color and texture parameters of refrigerated Caiman (Caiman crocodilus yacare) tail meat.
The effect of applying high hydrostatic pressure (HHP) on the instrumental parameters of color and texture and sensory characteristics of alligator meat were evaluated. Samples of alligator tail meat were sliced, vacuum-packed, pressurized and distributed into four groups: control, treated with 200 MPa/10 min, 300 MPa/10 min and 400 MPa/10 min, then stored at 4°C±1°C for 45 days. Instrumental color, texture profile and a sensory profiling using quantitative descriptive analysis were carried out on the 1st, 15th, 30th and 45th days of storage. HHP was shown to affect the color and texture of the product, and the sensory descriptors (p<0.05). The results suggest that high pressure is a promising technology for the processing of alligator meat, especially low pressures (200 MPa) which can have positive effects on the quality of the product.


Novel PAMs Targeting NMDAR GluN2A Subunit.
In this issue of Neuron, Hackos et al. (2016) report the discovery of novel positive allosteric modulators that are highly selective for GluN2A-containing NMDA receptors. This novel class of PAMs shows distinct effects on synaptic plasticity.


Applications for release by Australians in Victoria found not guilty of offences of violence by reason of mental impairment.
Much research in relation to mental illness and the law has concentrated upon when accused persons are entitled to avail themselves of the defence of not guilty by reason of insanity or mental impairment. However, the decision as to when persons found not guilty by such pleas should be released step by step back into the community involves difficult analyses of the risk of recidivism by persons who have committed serious acts of violence whilst mentally ill. This article analyses some 70 cases heard by the Supreme Court of Victoria in Australia since the jurisdiction to make such decisions has been transferred from the executive arm of government to the judiciary. The jurisprudence generated by the Victorian Supreme Court constitutes Australia's most developed law in relation to prediction of dangerousness. This article evaluates the different and subtle dynamics that have influenced the judges in an increasingly sophisticated way to grapple with the phenomenon of mental illness in deciding when persons who have already killed can safely be released from involuntary detention status within the confines of a forensic psychiatric institution back into the general community.


Real-world performance of blood-based proteomic profiling in first-line immunotherapy treatment in advanced stage non-small cell lung cancer.
Immune checkpoint inhibition (ICI) therapy has improved patient outcomes in advanced non-small cell lung cancer (NSCLC), but better biomarkers are needed. A clinically validated, blood-based proteomic test, or host immune classifier (HIC), was assessed for its ability to predict ICI therapy outcomes in this real-world, prospectively designed, observational study. The prospectively designed, observational registry study INSIGHT (Clinical Effectiveness Assessment of VeriStrat® Testing and Validation of Immunotherapy Tests in NSCLC Subjects) (NCT03289780) includes 35 US sites having enrolled over 3570 NSCLC patients at any stage and line of therapy. After enrolment and prior to therapy initiation, all patients are tested and designated HIC-Hot (HIC-H) or HIC-Cold (HIC-C). A prespecified interim analysis was performed after 1-year follow-up with the first 2000 enrolled patients. We report the overall survival (OS) of patients with advanced stage (IIIB and IV) NSCLC treated in the first-line (ICI-containing therapies n=284; all first-line therapies n=877), by treatment type and in HIC-defined subgroups. OS for HIC-H patients was longer than OS for HIC-C patients across treatment regimens, including ICI. For patients treated with all ICI regimens, median OS was not reached (95% CI 15.4 to undefined months) for HIC-H (n=196) vs 5.0 months (95% CI 2.9 to 6.4) for HIC-C patients (n=88); HR=0.38 (95% CI 0.27 to 0.53), p<0.0001. For ICI monotherapy, OS was 16.8 vs 2.8 months (HR=0.36 (95% CI 0.22 to 0.58), p<0.0001) and for ICI with chemotherapy OS was unreached vs 6.4 months (HR=0.41 (95% CI 0.26 to 0.67), p=0.0003). HIC results were independent of programmed death ligand 1 (PD-L1). In a subgroup with PD-L1 ≥50% and performance status 0-1, HIC stratified survival significantly for ICI monotherapy but not ICI with chemotherapy. Blood-based HIC proteomic testing provides clinically meaningful information for immunotherapy treatment decision in NSCLC independent of PD-L1. The data suggest that HIC-C patients should not be treated with ICI alone regardless of their PD-L1 expression.


Spillover and spillback risks of ectoparasites by an invasive squirrel Callosciurus erythraeus in Kanto region of Japan.
Invasive organisms can alter host-parasite relationships in a given ecosystem by spreading exotic parasites and/or becoming a new reservoir for native ones. Since these problems affect management programs of the invasive host organisms, it is necessary to monitor them individually. The Pallas's squirrel Callosciurus erythraeus is an invasive arboreal mammal introduced into Japan that threatens to exacerbate ecological and public health problems by spreading native and exotic parasites. However, only limited surveys have been available especially for ectoparasites, using the traditional combing method in which the possibility of oversight is inherent. Here, we evaluated the ectoparasite occurrences in Kanto region of Japan, using the whole-shaving method as an alternative approach. As a result of examining 52 hosts from two invaded districts (Yokohama and Yokosuka), chigger mites (Leptotrombidium spp.) and fleas (Ceratophyllus anisus and Ceratophyllus indages indages) were newly recovered in addition to the previously reported tick (Haemaphysalis flava) and exotic lice (Enderleinellus kumadai and Neophaematoponis callosciuri). The parasite burdens were higher in Yokosuka and in male host individuals, affecting infracommunity richness and composition. Our findings on the variety of native and exotic ectoparasites, at higher abundances in some cases than previously known, may suggest that both the spillover and spillback risks need to be adjusted upwards.


11 cm Haughton D left cervical aortic arch aneurysm.
A 56 year old Caucasian man presented with sudden loss of consciousness while driving and was found to have an 11 cm Haughton D type left cervical aortic arch aneurysm with normal brachiocephalic branching and normal descending thoracic laterality but with considerable tortuosity and redundancy of aortic arch. The aneurysm arose between the left common carotid artery and the left subclavian artery. It compressed and stretched the left common carotid artery, compressed the pulmonary trunk and the left pulmonary artery, stretched the vagus, left recurrent laryngeal and left phrenic nerves and caused extreme deviation of trachea, severely compromising the tracheal lumen. Patient underwent successful interposition graft replacement of distal aortic arch under total circulatory arrest and selective unihemispherical cerebral perfusion.


A Bibliometric Analysis of the Top 100 Most Influential Studies on Robotic Arthroplasty.
The use of robotics in arthroplasty surgery has increased substantially in recent years. The purpose of this study was to objectively identify the 100 most influential studies in the robotic arthroplasty literature and to conduct a bibliometric analysis of these studies to describe their key characteristics. The Clarivate Analytics Web of Knowledge database was used to gather data and metrics for robotic arthroplasty research using Boolean queries. The search list was sorted in descending order by the number of citations, and articles were included or excluded based on clinical relevance to robotic arthroplasty. The top 100 studies were cited a total of 5770 times from 1997 to 2021, with rapid growth in both citation generation and the number of articles published occurring in the past 5 years. The top 100 robotic arthroplasty articles originated from 12 countries, with the United States being responsible for almost half of the top 100. The most common study types were comparative studies (36) followed by case series (20), and the most common levels of evidence were III (23) and IV (33). Research on robotic arthroplasty is rapidly growing and originates from a wide variety of countries, academic institutions, and with significant industry influence. This article serves as a reference to direct orthopaedic practitioners to the 100 most influential studies in robotic arthroplasty. We hope that these 100 studies and the analysis we provide aid healthcare professionals in efficiently assessing consensus, trends, and needs within the field.


Immunochemical studies of acrylamide-associated neuropathology.
An immunohistochemical study on neurofilaments (NF) in the central and peripheral nervous systems of rats after repeated treatment with acrylamide was done by the avidin-biotin complex method using monoclonal anti-neurofilaments antibodies (68, 160 and 200 kD). Rats were given acrylamide (50 ml/kg) i.p. every day for 8 days. In the cerebrum, NF in perikarya of large nerve cells were weakly stained with all antibodies in both control and treated rats, with no differences between the 2 groups. In the cerebellum, NF of the Purkinje cells were slightly stained with all 3 antibodies. In the treated rats, a marked accumulation of NF in the distal part of the basket cell fibers was detected by 68 kD. In the molecular layer, some parallel fibers were also stained by 68 kD in the treated animals. In the spinal cord, all NF were stained, the staining being clearer in the lower part of the cord in the treated rats. In the peripheral nerve of the treated rats, many axons were segmentally swollen along the entire length of the nerve, especially, in the distal region. In muscle preparations of the treated rats, some neuro-muscular junctions stained with 68 kD were also visible.


Natural history of diverticular disease: when to operate?
The natural history of patients admitted because of acute diverticulitis is largely unknown, and the selection of patients for surgical treatment varies notably. This study presents our experience concerning the outcome for 366 patients admitted during a 10-year period. Three hundred sixty-six patients admitted to our hospital with acute diverticulitis from 1981 to 1990 were identified from a computer database, and their clinical data up to the end of 1996 were reviewed from the database and patient records. There were significantly more males than females in the age group less than 50 years old, and young males underwent surgical treatment during the first treatment period more frequently than the others. Young patients were operated on without mortality, and all their temporary colostomies were closed. Older patients died more often of diseases unrelated to the diverticular disease during the years after the first episode of acute diverticulitis. Recurrences of diverticular disease developed in 22 percent of patients, and they were significantly more common in patients less than 50 years old than in the older age groups. Males less than 50 years old more often developed complications of diverticular disease after two hospital admissions. Males first admitted when less than 50 years of age undergo more primary operations and develop more recurrences of diverticular disease than do older people. Based on our data, however, we recommend surgery for all patients after two episodes of acute diverticulitis that resolves after conservative treatment with antibiotics.


Mature follicular dendritic cell networks depend on expression of lymphotoxin beta receptor by radioresistant stromal cells and of lymphotoxin beta and tumor necrosis factor by B cells.
The formation of germinal centers (GCs) represents a crucial step in the humoral immune response. Recent studies using gene-targeted mice have revealed that the cytokines tumor necrosis factor (TNF), lymphotoxin (LT) alpha, and LTbeta, as well as their receptors TNF receptor p55 (TNFRp55) and LTbetaR play essential roles in the development of GCs. To establish in which cell types expression of LTbetaR, LTbeta, and TNF is required for GC formation, LTbetaR-/-, LTbeta-/-, TNF-/-, B cell-deficient (BCR-/-), and wild-type mice were used to generate reciprocal or mixed bone marrow (BM) chimeric mice. GCs, herein defined as peanut agglutinin-binding (PNA+) clusters of centroblasts/centrocytes in association with follicular dendritic cell (FDC) networks, were not detectable in LTbetaR-/- hosts after transfer of wild-type BM. In contrast, the GC reaction was restored in LTbeta-/- hosts reconstituted with either wild-type or LTbetaR-/- BM. In BCR-/- recipients reconstituted with compound LTbeta-/-/BCR-/- or TNF-/-/BCR-/- BM grafts, PNA+ cell clusters formed in splenic follicles, but associated FDC networks were strongly reduced or absent. Thus, development of splenic FDC networks depends on expression of LTbeta and TNF by B lymphocytes and LTbetaR by radioresistant stromal cells.


An analysis of student essays on medical leadership and its educational implications in South Korea.
To examine medical students' perceptions of leadership and explore their implications for medical leadership education. We conducted a qualitative analysis of the essays submitted by students in the medical leadership course from 2015 to 2019. We categorised the essays by the characteristics of the selected model leaders (N = 563) and types of leadership (N = 605). A statistically significant proportion of students selected leaders who were of the same gender as themselves (P < 0.001), graduate track students chose leaders in science (P = 0.005), while; military track students chose leaders in the military (P < 0.001). Although the highest proportion of students chose politicians as their model leaders (22.7%), this number decreased over time (P < 0.001), and a wider range of occupational groups were represented between 2015 and 2019. Charismatic leadership was the most frequently selected (31.9%), and over time there was a statistically significant (P = 0.004) increase in the selection of transformational leadership. Students tended to choose individuals whose acts of leadership could be seen and applied. Medical leadership education should account for students' changing perceptions and present a feasible leadership model, introducing specific examples to illustrate these leadership skills.


Eosinophilic esophagitis: diagnosis and management.
Eosinophilic esophagitis is a clinicopathologic disease that can present with a constellation of upper gastrointestinal symptoms and endoscopic findings in conjunction with significant infiltration of the esophageal tissue with eosinophils. Clinical and histologic resolution of the disease can be seen with dietary restriction therapies and systemic and topical corticosteroids. Because most patients have an atopic background and the disease seems to have an underlying T-helper type 2 pathogenesis, allergists and gastroenterologists need to be familiar with the diagnosis and management of this disease. In this review, clinical characteristics, endoscopic and histologic findings, and available therapy options are discussed.


Gentianose: Purification and structural determination of an unknown oligosaccharide in grape seeds.
Grape seeds are among the main constituents of grape pomace, ranging between 20% and 30% of the wet matrix; however, their oligosaccharide composition has not been studied. This paper describes the purification and the identification of low molecular weight oligosaccharides contained in an EtOH/water extract of grape seeds. A sequential two-step purification by size exclusion chromatography was carried out to fractionate compounds according to molecular weights. Chemical characterization of the combined fractions was performed by Magnetic Resonance Spectroscopy and Gas Chromatography-Mass Spectrometry analyses. The separation process gave two fractions abundant in sucrose and glucose. A third fraction containing trisaccharides was acetylated allowing the purification of the main trisaccharide. The structure elucidation of the acetylated product made it possible to identify gentianose, a predominant carbohydrate reserve found in the storage roots of perennial Gentiana lutea. Grape seeds are wine industry by-products and the obtained results suggest the importance of their recovery.


Alpha-oxidation of 3-methyl-substituted fatty acids in rat liver.
3-Methyl-substituted fatty acids are first oxidatively decarboxylated (alpha-oxidation) before they are degraded further via beta-oxidation. We synthesized [1-14C]phytanic and 3-[1-14C]methylmargaric acids in order to study their alpha-oxidation in isolated rat hepatocytes, rat liver homogenates and subcellular fractions. alpha-Oxidation was measured as the production of radioactive CO2. In isolated hepatocytes, maximal rates of alpha-oxidation amounted to 7 and 10 nmol/min x 10(8) cells with phytanic acid and 3-methylmargaric acid, respectively. At equimolar substrate concentrations, alpha-oxidation of branched fatty acids was approximately 10- to 15-fold slower than the beta-oxidation of the straight chain palmitate. In whole liver homogenates, rates of alpha-oxidation that equaled 60 to 70% of those observed in the hepatocytes were obtained. Optimum rates required O2, NADPH, Fe3+, and ATP. Fe3+ could be replaced by Fe2+ and ATP could be replaced by a number of other phosphorylated nucleosides and even inorganic phosphate without loss of activity. NADH could substitute for NADPH but not always with full restoration of activity. A variety of other cofactors and metal ions was either inhibitory or without effect. Scavengers of reactive oxygen species, known to be formed during the NADPH-dependent microsomal reduction of ferric-phosphate complexes, were without effect on alpha-oxidation. No evidence was found for the accumulation of NADPH-dependent or Fe(3+)-dependent reaction intermediates. Subcellular fractionation of liver homogenates demonstrated that alpha-oxidation was located predominantly, if not exclusively, in the endoplasmic reticulum. alpha-Oxidation, measured in microsomal fractions, was not inhibited by CO, cytochrome c, or ferricyanide, indicating that NADPH cytochrome P450 reductase and cytochrome P450 are not involved in alpha-oxidation. Our results indicate that, contrary to current belief, alpha-oxidation is catalyzed by the endoplasmic reticulum. The cofactor requirements suggest that alpha-oxidation involves the reduction of Fe3+ by electrons from NADPH and that it is stimulated by phosphate ions and nucleotides.


Novel technology as platform for interventions for caregivers and individuals with severe mental health illnesses: A systematic review.
Severe mental illnesses (SMIs) have been found to be associated with both increases in morbidity-mortality, need for treatment care in patients themselves, and burden for relatives as caregivers. A growing number of web-based and mobile software applications have appeared that aim to address various barriers with respect to access to care. Our objective was to review and summarize recent advancements in such interventions for caregivers of individuals with a SMI. We conducted a systematic search for papers evaluating interactive mobile or web-based software (using no or only minimal support from a professional) specifically aimed at supporting informal caregivers. We also searched for those supporting patients with SMI so as to not to miss any which might include relatives. Out of a total of 1673 initial hits, we identified 11 articles reporting on 9 different mobile or web-based software programs. The main result is that none of those studies focused on caregivers, and the ones we identified using mobile or web-based applications were just for patients and not their relatives. Differentiating between online and offline available software might not always have been totally reliable, and we might have therefore missed some studies. In summary, the studies provided evidence that remotely accessible interventions for patients with SMI are feasible and acceptable to patients. No such empirically evaluated program was available for informal caregivers such as relatives. Keeping in mind the influential role of those informal caregivers in the process of treatment and self-management, this is highly relevant for public health. Supporting informal caregivers can improve well-being of both caregivers and patients.


Update of the classification of midpalatal suture behaviour after surgically assisted rapid maxillary expansion using computed tomography.
The aim of this study was to update the midpalatal suture classification after surgically assisted rapid maxillary expansion (SARME) using computed tomography (CT). Thirty-five patients with a transverse maxillary deficiency and unilateral or bilateral posterior crossbite underwent SARME with osteotomy of the pterygoid apophysis of the sphenoid. CT was performed before installation of the Hyrax expander appliance and after the final activation. Opening of the midpalatal suture was classified into three types: type I, total midpalatal suture opening from anterior nasal spine (ANS) to posterior nasal spine (PNS); type II, partial midpalatal suture opening from ANS to the transverse palatine suture, with partial or non-existent opening of the midpalatal suture posterior to the transverse palatine suture; type III, complete maxillary opening from ANS, but not of PNS, because a paramedian fracture completed the opening of the hard palate. Type I was observed in 42.8% of the patients, type II in 40%, and type III in 17.2%. Opening of the transverse palatine suture was found in all midpalatal suture opening patterns and was more frequent in type III, followed by type II and type I. CT was used to update the classification of midpalatal suture patterns, with the inclusion of type III: total opening of the hard palate due partly to opening of the midpalatal suture and partly to a paramedian fracture.


Artepillin C derived from propolis induces neurite outgrowth in PC12m3 cells via ERK and p38 MAPK pathways.
We investigated whether artepillin C, a major component of Brazilian propolis, acts as a neurotrophic-like factor in rat PC12m3 cells, in which nerve growth factor (NGF)-induced neurite outgrowth is impaired. When cultures of PC12m3 cells were treated with artepillin C at a concentration of 20 microM, the frequency of neurite outgrowth induced by artepillin C was approximately 7-fold greater than that induced by NGF alone. Artepillin C induced-neurite outgrowth of PC12m3 cells was inhibited by the ERK inhibitor U0126 and by the p38 MAPK inhibitor SB203580. Although artepillin C-induced p38 MAPK activity was detected in PC12m3 cells, phosphorylation of ERK induced by artepillin C was not observed. On the other hand, artepillin C caused rapid activation of ERK and the time course of the activation was similar to that induced by NGF treatment in PC12 parental cells. However, NGF-induced neurite outgrowth was inhibited by artepillin C treatment. Interestingly, inhibition of ERK by U0126 completely prevented artepillin C-induced p38 MAPK phosphorylation of PC12m3 cells. These findings suggest that artepillin C-induced activation of p38 MAPK through the ERK signaling pathway is responsible for the neurite outgrowth of PC12m3 cells.


Radionuclide exploration of dialysis amyloidosis: preliminary experience.
The noninvasive diagnosis of amyloid arthropathy in dialysis patients is still uncertain. Therefore, we investigated the potential diagnostic value of the 99mTc-methylene diphosphonate scan in seven long-term hemodialysis patients suffering from chronic joint pain who had biopsy-proven osteoarticular amyloidosis of the recently discovered beta 2-microglobulin (beta 2-M) type. In six, but in none of five control patients on short-term hemodialysis, increased tracer uptake was found at the site of one or several articular and/or periarticular regions. Increased uptake at a given joint was often, but not always, associated with joint pain. It appeared to precede radiologically visible changes. In conclusion, the 99mTc-methylene diphosphonate scan may be of help in the early diagnosis of dialysis amyloidosis.


Joint effects of climate variability and socioecological factors on dengue transmission: epidemiological evidence.
To assess the epidemiological evidence on the joint effects of climate variability and socioecological factors on dengue transmission. Following PRISMA guidelines, a detailed literature search was conducted in PubMed, Web of Science and Scopus. Peer-reviewed, freely available and full-text articles, considering both climate and socioecological factors in relation to dengue, published in English from January 1993 to October 2015 were included in this review. Twenty studies have met the inclusion criteria and assessed the impact of both climatic and socioecological factors on dengue dynamics. Among those, four studies have further investigated the relative importance of climate variability and socioecological factors on dengue transmission. A few studies also developed predictive models including both climatic and socioecological factors. Due to insufficient data, methodological issues and contextual variability of the studies, it is hard to draw conclusion on the joint effects of climate variability and socioecological factors on dengue transmission. Future research should take into account socioecological factors in combination with climate variables for a better understanding of the complex nature of dengue transmission as well as for improving the predictive capability of dengue forecasting models, to develop effective and reliable early warning systems.


Perceived problems with involvement in decision making about breast cancer treatment and care: A cross-sectional study.
To examine perceived problems with involvement in medical decision making among people with breast cancer from various phases of the cancer care trajectory. Breast cancer outpatients (n = 663) from 13 treatment centres completed a survey of perceived involvement in treatment and care decisions in the last month, psychological distress, demographic and clinical factors. A subsample (n = 98) from three centres completed a follow-up survey on preferred and perceived treatment decision making roles. Overall, 112 (17 %) of 663 respondents from 13 oncology centres had experienced problems with involvement in decision making about their treatment and care in the last month, and of these, 36 (32 %) reported an unmet need for help with this problem. Elevated psychological distress was associated with 5.7 times the odds of reporting this problem and 6.6 times the odds of reporting this unmet need in the last month. Among the follow-up subsample (n = 98), 39% (n = 38) reported discordance between preferred and perceived role in a major treatment decision. Psychological distress was not associated with this outcome. Psychological distress was significantly associated with recently experiencing problems with involvement in treatment and care decisions, but not with misalignment of preferred and perceived roles in prior major treatment decisions. There is a need to maintain support for patient involvement in healthcare decisions across the cancer care continuum.


Associations between intrinsic capacity, functional difficulty, and fall outcomes among older adults in India.
The construct of intrinsic capacity (IC) in the context of integrated care for older adults emphasizes functional assessment from a holistic perspective. It provides reliable and comparable insights on subsequent functioning and disability. Given the paucity of research on IC and health outcomes in low- and middle-income countries (LMICs), the present study examined the association of IC with geriatric conditions of functional limitations and multiple fall outcomes among older adults in India. The data used for analysis come from the first wave of the Longitudinal Aging Study in India (LASI), 2017-2018. The final sample size contains 24,136 older adults (11,871 males and 12,265 females) age 60 years or above. Multivariable binary logistic regression is employed to examine the association of IC and other explanatory factors with outcome variables of difficulty in activities of daily living (ADL) and instrumental activities of daily living (IADL), falls, fall injury, and multiple falls. Of the total sample, 24.56% of older adults were observed to be in the high IC category. The prevalence of ADL difficulty, IADL difficulty, falls, multiple falls and fall-related injury is estimated to be 19.89%, 45.00%, 12.36%, 5.49% and 5.57%, respectively. Older adults who reported high IC had a significantly lower prevalence of ADL difficulty (12.26% vs 22.38%) and IADL difficulty (31.13% vs 49.52%) than those who reported low IC. Similarly, a lower prevalence of falls (9.42% vs 13.34%), fall-related injury (4.10% vs 6.06%) and multiple falls (3.46% vs 6.16%) were reported among those who had high IC. After adjusting for a large number of confounders such as age, sex, health-related attributes and lifestyle behaviors, older adults with high IC had significantly lower odds of ADL difficulty [aOR: 0.63, CI: 0.52-0.76], IADL difficulty [aOR: 0.71, CI: 0.60-0.83], falls [aOR: 0.80, CI: 0.67-0.96], multiple falls [aOR: 0.73, CI: 0.58-0.96] and fall-related injury [aOR: 0.78, CI: 0.61-0.99]. That a high IC was independently associated with a lower risk of functional difficulty and fall outcomes in later life is of enormous value in predicting subsequent functional care needs. More specifically, the findings here imply that because regular IC monitoring can predict poor health outcomes in older adults, improvements in IC should be prioritized while formulating disability and fall prevention strategies.


Midface sculpting with autologous fat.
There is currently a major paradigm shift from excision-based surgery to strictly volume enhancement. Because there is still no perfect facial filler, development of synthetic facial injectables continue to advance at a remarkable pace. Each type of filler carries a specific characteristic that makes it more suitable for a certain clinical application. The continuing change in facial fillers offers the possibility for volume augmentation procedures with less downtime and without the need for harvesting fat. We predict that volume enhancement will continue to play an increasing role as both a complementary and as a stand-alone procedure in facial rejuvenation.


Prevalence of glaucoma in the Northern Finland Birth Cohort Eye Study.
To report the prevalence of glaucoma in the Northern Finland Birth Cohort (NFBC) Eye Study. Subjects of the population-based Northern Finland 1966 Birth Cohort (NFBC), aged 45-49 years at the time of the field examination, were randomized to eye screening (50%) and control (50%) groups. The eye examination protocol included best corrected visual acuity (BCVA), measurements of intraocular pressure and central corneal thickness, Humphrey 24-2 perimetry, stereoscopic optic nerve head (ONH) and retinal nerve fibre layer (RNFL) photography and imaging with optical coherence tomography (OCT), scanning laser polarimetry (GDx) and scanning laser ophthalmoscopy (HRT). The diagnosis of glaucoma was made by two independent general ophthalmologists and three independent glaucoma experts based on the evaluation of the ONH and RNFL photographs and the visual fields. Totally, 10 321 subjects of the NFBC main study were alive in Finland in 2011, and they were randomized to the NFBC Eye Study group (n = 5155) and the control group (n = 5166). Of the randomized subjects, 3039 of 5155 (59%) responded and had sufficient data for the study. Glaucoma was suspected in 172 subjects (5.7%) at the first phase of the evaluation protocol. The interobserver agreement between two screening ophthalmologists was moderately good (kappa value 0.54 [95% confidence intervals (CI) 0.46-0.61]). Finally, definite glaucoma was found in 33 subjects (1.1% [95% CI 0.8-1.5]). The study provides up-to-date information on the prevalence of glaucoma in a middle-aged Caucasian population in Finland. The baseline data reported here allows the evaluation of the cost-effectiveness of screening later on.


CuInSe2 nanotube arrays for efficient solar energy conversion.
Highly uniform and vertically aligned p-type CuInSe2 (CISe) nanotube arrays were fabricated through a unique protocol, incorporating confined electrodeposition on lithographically patterned nanoelectrodes. This protocol can be readily adapted to fabricate nanotube arrays of other photoabsorber and functional materials with precisely controllable design parameters. Ternary CISe nanotube arrays were electrodeposited congruently from a single electrolytic bath and the resulting nanotube arrays were studied through powder X-ray diffraction as well as elemental analysis which revealed compositional purity. Detailed photoelectrochemical (PEC) characterizations in a liquid junction cell were also carried out to investigate the photoconversion efficiency. It was observed that the tubular geometry had a strong influence on the photocurrent response and a 29.9% improvement of the photoconversion efficiency was observed with the nanotube array compared to a thin film geometry fabricated by the same process. More interestingly such enhancement in photoconversion efficiency was obtained when the electrode coverage with the nanotube arrays as photoactive material was only a fraction (~10%) of that for the thin film device. Apart from enhancement in photoconversion efficiency, this versatile technique provides ample opportunities to study novel photovoltaic materials and device design architectures where structural parameters play a key role such as resonant light trapping.


Long-term investing and your bond rating.
Days cash on hand is an important measure of a healthcare organization's financial condition--but not the only one. A well-diversified investment portfolio managed against long-term objectives is equally important--and can be a significant asset in the eyes of bond rating agencies.


A universal SI-traceable isotope dilution mass spectrometry method for protein quantitation in a matrix by tandem mass tag technology.
Isotope dilution mass spectrometry (IDMS), an important metrological method, is widely used for absolute quantification of peptides and proteins. IDMS employs an isotope-labeled peptide or protein as an internal standard although the use of a protein provides improved accuracy. Generally, the isotope-labeled protein is obtained by stable isotope labeling by amino acids in cell culture (SILAC) technology. However, SILAC is expensive, laborious, and time-consuming. To overcome these drawbacks, a novel universal SI-traceable IDMS method for absolute quantification of proteins in a matrix is described with human transferrin (hTRF). The hTRF and a human serum sample were labeled with different tandem mass tags (TMTs). After mixing the TMT-labeled hTRF and serum sample together followed by digestion, the peptides were separated by nano-liquid chromatography and analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Using the signature peptides, we calculated the ratios of reporter ions from the TMT-labeled peptides which, in turn, allowed determination of the mass fraction of hTRF. The recovery ranged from 97% to 105% with a CV of 3.9%. The LOD and LOQ were 1.71 × 10(-5) g/g and 5.69 × 10(-5) g/g of hTRF in human serum, respectively, and the relative expanded uncertainty was 4.7% with a mass fraction of 2.08 mg/g. For comparison, an enzyme-linked immunosorbent assay (ELISA) method for hTRF yielded a mass fraction of 2.03 mg/g. This method provides a starting point for establishing IDMS technology to accurately determine the mass fractions of protein biomarkers in a matrix with traceability to SI units. This technology should support the development of a metrological method useful for quantification of a wide variety of proteins.


The pudendal nerve block for ambulatory urology: What's old is new again. A quality improvement project.
Caudal epidural analgesia (CEA) is a common analgesic technique performed for pediatric penile surgeries; however, it has associated morbidity. The pudendal nerve block (PNB) has been described as an effective analgesic alternative to CEA. In this quality improvement study, we aim to assess the efficacy of PNB as compared to CEA within our ambulatory surgery center (ASC). We demonstrate our initial experience employing PNB for ambulatory pediatric urology procedures. Using retrospective, non-randomized, time-series, observational data, a comparative effectiveness study of CEA and PNB was performed. Patients less than three years old, who underwent circumcision, hypospadias repair, congenital chordee repair, correction of penile angulation/torsion, and buried penis repair with or without scrotoplasty, between January 1, 2015-September 9, 2019 with either CEA or PNB in an ASC at a single institution were included. Standard protocols for local and postoperative analgesia were used. Outcome measures were post anesthesia care unit (PACU) pain scores, morphine rescue rates, and PACU length of stay (LOS). These were analyzed using statistical process control (SPC) charts; standard SPC rules were used to detect special cause variation. A total of 999 patients were identified; 746 (74.7%), 172 (17.2%) and 81 (8.1%) received CEA, ultrasound guided PNB (US-PNB) and landmark directed PNB (LD-PNB), respectively. Demographic data was comparable between the three cohorts. There was no special cause variation in the outcome measures between the CEA, US-PNB and LD-PNB cohorts for maximum pain score, morphine rescue rates and PACU LOS. Pain outcomes and PACU LOS were similar between the CEA, US-PNB and LD-PNB cohorts, suggesting equivalent postoperative pain control between these techniques within our cohort. Previous published data has reported lower postoperative pain scores with PNB as compared to CEA for patients undergoing circumcision and hypospadias repair. PNB is non-inferior to CEA for analgesia for pediatric penile surgery, with LD-PNB being as effective as US-PNB. Given the simplicity and documented lower risk profile, PNB may be preferred to CEA for ambulatory pediatric urology procedures.


No reduction in motor-evoked potential amplitude during the rubber hand illusion.
In the rubber hand illusion (RHI), touches are applied to a fake hand at the same time as touches are applied to a participant's real hand that is hidden in a congruent position. Synchronous (but not asynchronous) tactile stimulation of the two hands may induce the sensation that the fake hand is the participant's own. As such, the illusion is commonly used to examine the sense of body ownership. Some studies indicate that in addition to the subjective experience of limb ownership reported by participants, the RHI can also reduce corticospinal excitability (e.g., as reflected in motor-evoked potential [MEP] amplitude) and alter parietal-motor cortical connectivity in passive participants. These findings have been taken to support a link between motor cortical processing and the subjective experience of body ownership. In this study, we tried to replicate the reduction in MEP amplitude associated with the RHI and uncover the components of the illusion that might explain these changes. As such, we used single-pulse transcranial magnetic stimulation to probe the excitability of the corticospinal motor system as participants experienced the RHI. Despite participants reporting the presence of the illusion and showing shifts in perceived real hand position towards the fake limb supporting its elicitation, we did not observe any associated reduction in MEP amplitude. We conclude that a reduction in MEP amplitude is not a reliable outcome of the RHI and argue that if such effects do occur, they are unlikely to be large or functionally relevant.


Optimal choice on prevention and cure: a new economic analysis.
This paper studies choices on prevention and cure in a context where an agent bears a health risk. In this framework we first analyze interdependence between the optimal levels of prevention and cure. Second, we study the effects on optimal choices of a change in the cost of one of the two instruments and we examine substitutability between them. Finally we present findings about the effects of a change either in the seriousness of the possible disease or in the efficiency of the medical treatment.


Comprehensive proteomic and metabolomic profiling of mcr-1-mediated colistin resistance in Escherichia coli.
Spread of the mcr-1 gene in human and veterinary medicine has jeopardised the use of polymyxins, last-resort antibiotics against life-threatening multidrug-resistant Gram-negative bacteria. As a lipid-modifying gene, whether mcr-1 causes proteomic and metabolomic changes in bacteria and affects the corresponding metabolic pathway is largely unknown. In this study, label-free quantitative proteomics and untargeted metabolomics were used to profile comprehensive proteome and metabolome characteristics of mcr-1-mediated colistin-resistant and -susceptible Escherichia coli in order to gain further insight into the colistin resistance mechanism. Large sets of differentially expressed proteins (DEPs) and metabolites were identified that contributed to mcr-1-mediated antimicrobial resistance, predominantly in different growth conditions with and without colistin. mcr-1 caused downregulated expression of most proteins in order to adapt to drug pressure. Pathway analysis showed that metabolic processes were significantly affected, mainly related to glycerophospholipid metabolism, thiamine metabolism and lipopolysaccharide (LPS) biosynthesis. The substrate phosphoethanolamine (PEA) for mcr-1 to mediate colistin resistance was accumulated in colistin-resistant E. coli. Notably, mcr-1 not only caused PEA modification of the bacterial cell membrane lipid A but also affected the biosynthesis and transport of lipoprotein in colistin resistance by disturbing the expression of efflux pump proteins involved in the cationic antimicrobial peptide (CAMP) resistance pathway. Overall, disturbed glycerophospholipid metabolism and LPS biosynthesis as well as accumulation of the substrate PEA was closely related with mcr-1-mediated colistin resistance. These findings could provide further valuable information to inhibit colistin resistance by blocking this metabolic process.


7-Methyl-1-phenyl-1,10-di-hydro-pyrazolo-[3,4-a]carbazole.
In the title mol-ecule, C20H15N3, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1082 (15) Å]. The pyrrole ring makes dihedral angles of 3.17 (8)/4.10 (9), 7.20 (9) and 44.62 (9)° with the fused benzene, pyrazole and phenyl rings, respectively. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming an infinite chain along [010]. Mol-ecules are further linked by nine π-π [centroid-centroid distances vary from 3.6864 (11) to 3.9802 (11) Å] and one C-H⋯π inter-action, forming a three-dimensional network.


Measuring Client Experiences of Motivational Interviewing during a Lifestyle Intervention.
The Client Evaluation of Motivational Interviewing was used to assess MI experiences in a predominantly female, African American sample from the Southeastern U.S. who received MI-based feedback during a multi-component lifestyle intervention. MI was experienced differently than a primarily White, male, Northeastern mental health sample.


Mining environmental toxicology information: web resources.
Environmental toxicology is the study of the ecological effects of anthropogenic substances released into the environment. It is a relatively diverse field addressing impacts to aquatic and terrestrial organisms and communities. The determination of potential risk associated with toxic agents is of interest to government regulators, industry, researchers, private organizations and citizen groups. In assessing the ecological risk associated with a chemical stressor, it is important to establish linkages between likely exposure concentrations and adverse effects to ecological receptors. To do so requires access to reliable information resources. The proper application of such data requires familiarity with the scientific literature and keeping abreast of new and emerging issues as well as state-of-the-art research findings and methods. In addition, an understanding of government regulations as they relate to environmental issues is also of primary interest. The advent of the Web has made these tools accessible at computer desktops. This review focuses on currently available free Web resources related to environmental toxicology, specifically those which address available empirical data sources, predictive tools and publications of interest such as standard test methods, guidance documents and governmental regulations.


[Study of the synthesis of vitellogenin in intersexual males of Armadillidium vulgare Latreille (oniscoid isopod crustacean): comparison with males and with intact or ovariectomized females].
In some natural populations of Armadilidium vulgare, intersex animals are genetic males which are feminized by maternally transmitted symbiotic bacteria. In these intersex males (iM) the fat body synthesizes vitellogenin, although their gonads are testes with hypertrophied--but nonfunctional--androgenic glands. Vitellogenin is present in the hemolymph of males changed experimentally into iM 90 days after inoculation of the feminizing bacteria. During the molting cycle, vitellogenin synthesis in iM varies as in ovariectomized females or in vitellogenic females, with a peak at the stage D1." In A. vulgare, vitellogenin synthesis is a neutral character since it can be observed in a genetic male or in an ovariectomized female; however, it is inhibited by the androgenic hormone. In intersex males, vitellogenin synthesis is the result of their refractoriness to androgenic hormone.


Emerging Technologies for Detecting the Chemical Composition of Plant and Animal Tissues and Their Bioactivities: An Editorial.
Integrating physical and chemical technologies for the characterization and modification of plants and animal tissues has been used for several decades to improve their detection potency and quality [...].


Thrombospondin-1 prevents amyloid beta-mediated synaptic pathology in Alzheimer's disease.
Alzheimer's disease (AD) is characterized by impaired cognitive function and memory loss, which are often the result of synaptic pathology. Thrombospondin (TSP) is an astrocyte-secreted protein, well known for its function as a modulator of synaptogenesis and neurogenesis. Here, we investigated the effects of TSP-1 on AD pathogenesis. We found that the level of TSP-1 expression was decreased in AD brains. When we treated astrocytes with amyloid beta (Aβ), secreted TSP-1 was decreased in autophagy-dependent manner. In addition, treatment with Aβ induced synaptic pathology, such as decreased dendritic spine density and reduced synaptic activity. These effects were prevented by coincubation of TSP-1 with Aβ, which acts through the TSP-1 receptor alpha-2-delta-1 in neurons. Finally, intrasubicular injection with TSP-1 into AD model mouse brains mitigated the Aβ-mediated reduction of synaptic proteins and related signaling pathways. These results indicate that TSP-1 is a potential therapeutic target in AD pathogenesis.


Pharmacokinetics of furosemide in anephric patients and in normal subjects.
The pharmacokinetics of furosemide 40 mg i.v. were compared in 7 anephric patients and in 7 normal subjects. The average serum clearance was 66 ml/min in the patients and 219 ml/min in the normal subjects, and the corresponding weight corrected clearances were 1.33 ml/min . kg and 2.96 ml/min . kg. Binding to serum proteins was significantly decreased in the anephric subjects, in whom a significant negative correlation was found between the percentage binding and the volume of distribution VDSS. In the patients, but not in the normal subjects, there was a significant positive correlation between VDSS and serum clearance. Both in normal and anephric individuals 4-chlor-5-sulphamoyl-anthranilic-acid (CSA) was found, but there was no evidence of special accumulation either of CSA or anthranilic acid in the anephric patients. In the patients the initial increase in serum concentration of sodium and protein followed by a more conspicuous decrease were more pronounced, but none of the changes were statistically significant.


Modelling and parameter optimisation for performance evaluation of sequencing batch reactor for treating hospital wastewater.
Hospital wastewater treatment is gaining attention in recent studies due to its complex nature. The performance of the sequencing batch reactor coupled with tube-settler was investigated for hospital wastewater treatment. The performance was evaluated regarding removing organic matter and nutrients (nitrate and phosphate). The phosphate was removed in the sequencing batch reactor and its associated tube-settler with a 60% removal efficiency margin. Nitrification was observed in sequencing batch reactor and tube-settler, but denitrification could not be achieved. The nitrification-denitrification process was not completed during the process. The current work's main aim was to understand and optimise the operational parameters involved in the performance of the sequencing batch reactor. The operational parameters were optimised using Design expert software, and Response Surface Methodology involved a four-factor and five-level central composite design. The percentage removal of chemical oxygen demand, nitrate, and phosphate was selected to be observed during this study. The online version contains supplementary material available at 10.1007/s13399-022-03406-z.


Surface Ligand Density Switches Glycovesicles between Monomeric and Multimeric Lectin Recognition.
Carbohydrate-protein interactions define a multitude of cellular recognition events. We present herein synthetic glycovesicles as cell-surface mimics in order to switch the nature of lectin recognition. The covalent glycovesicles, constituted with diacetylene monomers of various ligand densities at their surfaces, are prepared through photo-polymerization. Vesicles with sparsely imbedded ligands engage in a lectin interaction leading to the formation of a dense, crosslinked multimeric complex. On the other hand, vesicles with many ligands, or completely covered with them, switch the lectin interaction to form a fully soluble monomeric complex, without crosslinking. Nanomolar dissociation constants govern these interactions, as assessed by a ligand-displacement assay. The study demonstrates the switching nature - between monomeric and multimeric - of the interaction as a function of ligand density in the vesicles; the results are directly relevant to understanding such a phenomenon occurring at cell surfaces.


Prolonged Automated Robotic TCD Monitoring in Acute Severe TBI: Study Design and Rationale.
Transcranial Doppler ultrasonography (TCD) is a portable, bedside, noninvasive diagnostic tool used for the real-time assessment of cerebral hemodynamics. Despite the evident utility of TCD and the ability of this technique to function as a stethoscope to the brain, its use has been limited to specialized centers because of the dearth of technical and clinical expertise required to acquire and interpret the cerebrovascular parameters. Additionally, the conventional pragmatic episodic TCD monitoring protocols lack dynamic real-time feedback to guide time-critical clinical interventions. Fortunately, with the recent advent of automated robotic TCD technology in conjunction with the automated software for TCD data processing, we now have the technology to automatically acquire TCD data and obtain clinically relevant information in real-time. By obviating the need for highly trained clinical personnel, this technology shows great promise toward a future of widespread noninvasive monitoring to guide clinical care in patients with acute brain injury. Here, we describe a proposal for a prospective observational multicenter clinical trial to evaluate the safety and feasibility of prolonged automated robotic TCD monitoring in patients with severe acute traumatic brain injury (TBI). We will enroll patients with severe non-penetrating TBI with concomitant invasive multimodal monitoring including, intracranial pressure, brain tissue oxygenation, and brain temperature monitoring as part of standard of care in centers with varying degrees of TCD availability and experience. Additionally, we propose to evaluate the correlation of pertinent TCD-based cerebral autoregulation indices such as the critical closing pressure, and the pressure reactivity index with the brain tissue oxygenation values obtained invasively. The overarching goal of this study is to establish safety and feasibility of prolonged automated TCD monitoring for patients with TBI in the intensive care unit and identify clinically meaningful and pragmatic noninvasive targets for future interventions.


An in vivo histopathological comparison of single and double pulsed modes of a fractionated CO(2) laser.
Studies examining the histopathological changes that occur in human skin following fractional laser treatment have been performed mainly in animals or abdominal tissue prior to abdominoplasty. This study looks at the effect of double pulse fractional CO(2) laser compared to single pulse treatments to assess differences in tissue injury in the face and abdomen. Twelve healthy subjects randomized into two groups, had two 1 cm(2) areas (infraumbilical and forehead) treated with the fractional CO(2) laser (Deep Fx, Lumenis). Settings used were 15 mJ double pulse, and 30 mJ single pulse, 300 Hz, 10% density and compared to the historic control of 15 patients treated at 15 mJ single pulse [Bailey et al. (2011), Lasers Surg Med 43: 99-107]. Treated sites were biopsied and analyzed with H&E and TUNEL staining to measure width and depth of the microthermal zones (MTZ) of ablation. When comparing 15 mJ double pulse to single pulse there were significant differences both in depth (abdominal skin, P = 0.002 and facial skin, P = 0.001) and width (facial skin, P = 0.0002) of MTZ. When comparing double pulsing at 15 mJ with single pulsing at 30 mJ there were significant differences between MTZ depths in the abdomen (P < 0.01) but not in either the MTZ depth (P = 0.69) or the width in the face (P = 0.502). This study demonstrates the differences between histopathological laser injury patterns in the face compared to the abdomen when single pulsing is used. It also demonstrates that double pulsing at 15 mJ is statistically similar to single pulsing at 30 mJ in the face. We think this could have ramifications for clinical practice where by double pulsing at lower energies may result in better clinical outcomes than increasing energies or using multiple passes at single pulse. Clinical studies needs to be performed to investigate this further.


Effects of dietary Plantago ovata seed extract administration on growth performance and immune function of common carp (Cyprinus carpio) fingerling exposed to ammonia toxicity.
Medicinal plants are powerful antioxidants which can improve well-being and suppress oxidative stress caused by environmental toxins in aquatic animals. In this regard, the present research was designed to show the potential effects of psyllium (Plantago ovata) seed extract (PSE) on the growth, and immune responses of common carp Cyprinus carpio exposed to acute ammonia toxicity. To perform the study, fish were fed with diets containing 0 (T0), 0.25 (T1), 0.5 (T2), and 1% (T3) PSE for 60 days, and then exposed to ammonia (0.5 mg L-1) for 3 h. The findings showed that fish given the T1 diet outperformed the T3 and control groups in terms of ultimate weight, weight increase, and food conversion ratio. Additionally, the T1 group showed a significantly higher level of total protein and serum lysozyme activity than the other treatment groups. Moreover, the highest serum total immunoglobulin values were recorded in T1 and T2 groups. The results showed that PSE, especially at moderate levels, could successfully upregulate the transcription of immune-related genes (IFN-γ, Hsp70, TNF-ɑ, IL-1ß, IL-10, and IgE) compared to the control group after exposure to ammonia. Furthermore, improving ammonia-induced down regulations of antioxidant-related gene expressions (CYP1A, SOD, and GPX) was observed in fish fed with PSE-included diets compared to the control one. However, PSE-supplemented diets did not affect the mRNA expression level of CAT. Regarding tight junction-associated genes, the higher mRNA expression level of occludin was observed in the T1 group, whereas the downregulation of CLD3 gene occurred in all experimental groups. Conversely, significant upregulation of osmoregulation-associated gene (NKA) was recorded in all experimental groups compared to the control one. Therefore, the administration of PSE (0.25% of the diet) for 60 days is recommended to increase growth performance, improve health, and increase the resistance of common carp to oxidative stress caused by ammonia.


Resistance to insulin suppression of plasma free fatty acids in liver cirrhosis.
Insulin action on carbohydrate metabolism is known to be reduced in liver cirrhosis. However, little is known about the effect of insulin on free fatty acid (FFA) metabolism in these patients. To investigate this aspect we performed a two-step insulin euglycemic clamp in 11 cirrhotic patients and 6 controls. Insulin was infused at 0.25 mU/Kg min from 0 to 100 min and at 1 mU/Kg from 100 to 200 min. The FFA lowering capacity of insulin was studied during the first step; the glucose metabolizing capacity (M) was evaluated during the second step. In the cirrhotic patients, the M value was lower than in controls (3.91 +/- 0.48 vs 7.75 +/- 1.09 mg/kg/min, respectively). During the low insulin infusion, FFA and glycerol plasma levels were decreased in both groups. However, the ability of insulin to suppress plasma FFA and glycerol was lower in cirrhotics than in controls. In fact, at 100 min, FFA were 50% of basal values in cirrhotics and 20% in controls (p less than 0.01), while glycerol plasma levels decreased to 70% of basal values in patients and to 56% in controls. The slope of the linear regression obtained between Ln-FFA concentrations vs time was significantly less in cirrhotic patients than in controls (p less than 0.001). In addition, a positive correlation was found between the M value (r = 0.70; p less than 0.01) and the slope of the Ln-FFA in each patient. These findings suggest that in cirrhotic patients the effects of insulin on both FFA and glucose metabolism are reduced.


Effects of diquat and fomesafen applied alone and in combination with a nonylphenol polyethoxylate adjuvant on Lemna minor in aquatic indoor microcosms.
The influence of tank-mix adjuvants on pesticide toxicity remains largely unknown. Agral 90, a nonylphenol polyethoxylated tank-mix adjuvant, has been used with diquat (bipyridylium herbicide) and fomesafen (diphenyl-ether herbicide) in aquatic indoor microcosms in order to compare the toxicity of the single compounds and of binary herbicide-adjuvant mixtures to Lemna minor. Twenty-four microcosms were used and treatments were performed with substances alone or with herbicide-adjuvant binary mixtures, at two concentrations levels (44.4 and 222.2 microg/L for the herbicides, and 100 and 500 microg/L for Agral 90). Toxicity was assessed weekly for 1 month through growth measurements, as inferred from the relative frond number (RFN) and relative frond area (RFA). Concentrations of diquat and fomesafen in water and sediments were measured weekly. The herbicides showed very different behaviour in microcosms, with a rapid disappearance of diquat from the aqueous phase whereas fomesafen levels remained almost constant over time. Diquat strongly inhibited the growth of L. minor whereas fomesafen had no effect on plant growth. Presence of the adjuvant only slightly reduced the effect of the lowest concentration of diquat, probably as a result of dispersion of the herbicide at the water surface. It is concluded that tank-mix adjuvant designed to improve herbicide efficiency in the terrestrial environment did not have any effect on aquatic plants when applied to the aquatic environment.


Online administration of a pilot mindfulness-based intervention for adolescents: Feasibility, treatment perception and satisfaction.
Adolescents may be more vulnerable to COVID-19-related impacts and require long-term mental health care. Services that bolster emotion regulation, such as mindfulness-based interventions (MBIs) promote positive impacts on psychosocial outcomes and have high acceptability. No studies have assessed feasibility, treatment perceptions and satisfaction of online MBIs with adolescents. 56 moderate- and high-risk adolescent (m = 14.5 years, 66.1% female, 26.8% LatinX) participants tested the feasibility, treatment perceptions and satisfaction of an 8-session online MBI focused on observing non-judgmentally, attending to positivity, and self-soothing. The study achieved acceptable feasibility with high attendance (m = 5.75) and retention rates (87.5%). The moderate- vs. high-risk group reported significantly higher ratings of treatment perceptions (t = 2.03, p < .05, d = 0.60). Significant associations were found between increased pre-test depression and anxiety symptomology and reduced intervention utility (rs = -0.34 and -0.32, ps < .05). This study demonstrated feasibility, treatment perceptions and satisfaction of an online MBI for adolescents presenting with two risk levels. Higher-risk adolescents may need a higher-touch intervention than moderate-risk, who may be more likely to find online MBIs acceptable. The impact of adjunctive MBIs for adolescents on treatment attendance and mental health outcomes over longer periods is necessary to understand patterns in effective adolescent treatment options. The online version contains supplementary material available at 10.1007/s12144-022-03025-x.


Immunoradiometric assay of serum thyroid stimulating hormone (TSH) as a first-line test in a mixed hospital population.
An immunoradiometric assay of thyroid stimulating hormone (TSH-IRMA) was evaluated as a first-line test for the diagnosis of thyroid disease in a prospective study of 318 consecutive patients in a major city hospital. The results of TSH-IRMA were compared with the diagnoses made by means of our usual diagnostic methods. Based on previous studies a serum TSH level of 0.15 mU/l was chosen as cutoff limit for calculation of diagnostic performance. For patients with serum TSH greater than 5.0 mU/l the results of TSH-IRMA were in accordance with the results of our routine radioimmunoassay. Patients with serum TSH levels between 0.15 mU/l and 5.0 mU/l were euthyroid (the diagnostic sensitivity was 100%). Consequently, the final diagnosis could be made with one test and within two days for 88% of patients. Patients with serum TSH less than 0.15 mU/l needed supplementary tests since only 32% of these patients had thyrotoxicosis, 32% had a non-toxic goiter, and 36% had no thyroid disease.


Induction of the synthesis of an UV-absorbing substance in the green alga Prasiola stipitata.
The chlorophyte Prasiola stipitata produces a UV-absorbing substance with an absorption maximum at 324 nm. The wavelength-dependent induction of the synthesis of this substance was investigated using simulated solar radiation in combination with 15 cut-off and one broad-band filter. The algae were exposed from three different distances (89, 100 and 119 cm) to the solar simulator producing a maximum of 203.58, 1.24 and 46.86 W/m(2) and a minimum of 107.94, 0.64 and 24.44 W/m(2) irradiances for PAR, UV-B and UV-A, respectively. A polychromatic action spectrum was calculated from the pooled results showing a clear maximum at 300 nm in the long-wavelength UV-B range, but there is still some induction caused by UV-A and PAR. The ratio of the effectiveness from PAR to UV-A to UV-B amounts to 1:2:22.


Use of Visual Decision Aids in Physician-Patient Communication: A Pilot Investigation.
A risk calculator paired with a personalized decision aid (RC&DA) may foster shared decision-making in primary care. We assessed the feasibility of using an RC&DA with patients in a primary care outpatient clinic and patients' experiences regarding communication and decision-making. This pilot study was conducted with 15 patients of 3 primary care physicians at a clinic within a tertiary medical center. An atherosclerotic cardiovascular disease (ASCVD) risk calculator was used to generate a personalized RC&DA that displayed absolute 10-year risk information as an icon array graphic. Patient perceptions of utility of the RC&DA, preferences for decision-making, and uncertainty with risk reduction decisions were measured with a semi-structured interview. Patients reported that the RC&DA was easy to understand and knowledge gained was useful to modify their ASCVD risk. Patients used the RC&DA to make decisions and reported low uncertainty with those decisions. Our findings demonstrate the feasibility of, and positive patient experiences related to using, an RC&DA to facilitate shared decision-making between physicians and patients in an outpatient primary care setting.


Excision of mesenteric lymph nodes alters gut microbiota and impairs social dominance in adult mice.
Mesenteric lymph nodes (MLNs) are central in immune anatomy. MLNs are associated with the composition of gut microbiota, affecting the central system and immune system. Gut microbiota was found to differ among individuals of different social hierarchies. Nowadays, excision of MLNs is more frequently involved in gastrointestinal surgery; however, the potential side effects of excision of MLNs on social dominance are still unknown. MLNs were removed from male mice (7-8 weeks old). Four weeks after MLN removal, social dominance test was performed to investigate social dominance; hippocampal and serum interleukin (IL)-1β, IL-10, and tumor necrosis factor-alpha (TNF-α) were investigated; and histopathology was used to evaluate local inflammation of the ileum. The composition of the gut microbiota was then examined to understand the possible mechanism, and finally intraperitoneal injection of IL-10 was used to validate the effect of IL-10 on social dominance. There was a decrease in social dominance in the operation group compared to the control group, as well as a decrease in serum and hippocampal IL-10 levels, but no difference in serum and hippocampal IL-1β and TNF-α levels, and no local inflammation of the ileum after MLN removal. 16S rRNA sequencing analysis showed that the relative abundance of the class Clostridia was decreased in the operation group. This decrease was positively associated with serum IL-10 levels. Furthermore, intraperitoneal injection of IL-10 in a subset of mice increased social dominance. Our findings suggested that MLNs contributed to maintaining social dominance, which might be associated with reduced IL-10 and the imbalance of specific flora in gut microbiota.


Rhodotorula lamellibrachii sp. nov., a new yeast species from a tubeworm collected at the deep-sea floor in Sagami bay and its phylogenetic analysis.
A new species of the genus Rhodotorula was isolated from a tubeworm (Lamellibrachia sp.) collected at a depth of 1156 m in Sagami Bay, Japan. Strain SY-89 had physiological properties quite similar to R. aurantiaca. Two phylogenetic trees, one based on internal transcribed spacer (ITS) regions and 5.8S rDNA sequences and the other based on the D1/D2 region of the large subunit (26S) rDNA sequences, united strain SY-89 to the type strain of Sakaguchia dacryoides through a considerable evolutionary distance. Strain SY-89 was differentiated from S. dacryoides by the G+C content of the nuclear DNA and differences in the ability to utilize specific carbon and nitrogen compounds. The low complementarity of strain SY-89 DNA to that of the type strain of S. dacryoides confirmed that this strain was genetically unrelated to previously known species. The tubeworm isolates are described as R. lamellibrachii sp. nov. The type strain of R. lamellibrachii is strain SY-89 (= JCM 10907). R. lamellibrachii formed a cluster with Erythrobasidium hasegawianum, R. lactosa, S. dacryoides and Sporobolomyces elongatus on the ITS and 5.8S rDNA phylogenetic tree. These five species shared a signature sequence in 26S rDNA, although this relationship was not supported by phylogeny based on the D1/D2 region of 26S rDNA.


Management of sarcomas possibly involving the knee joint when to perform extra-articular resection of the knee joint and is it safe?
We reviewed the oncological and functional outcomes of patients treated for a primary sarcoma possibly involving the knee joint and present an algorithm to guide treatment. The records of 76 patients who had a primary bone or soft tissue sarcoma possibly invading the knee between 1996 and 2012 were identified. Mean age and follow-up was 32 years (9-74) and 64 months (12-195), respectively. Patients were grouped according to the resection (Intra-articular [IAR] vs. Extra-articular [EAR] vs. Amputation/rotationplasty) for survival and functional outcomes. Overall 5 and 10 year survival was 61% and 53%, respectively. No differences in survival were found between the 3 groups (p = 0.55). Sixteen patients developed local recurrence with no difference between the groups. Mean MSTS score was 24.5 (12-30). Mean flexion at final follow-up was 106° (70-130°). We conclude that EAR of the knee allows for good oncologic and functional outcomes but with an increased risk of complications compared to IAR. Intra-operative assessment of joint involvement can be done in patients where joint infiltration by the tumour is not clear to avoid an unnecessary EAR. For chondrosarcoma patients with joint involvement, an EAR should be carefully considered because they present a significantly higher local recurrence risk.


Clinical Risk Management in radiology. Part II: applied examples and concluding remarks.
With the aim of providing a clearer understanding of the tools used for evaluating risk in the radiological setting and how they are applied, this second part presents two practical examples. The first is a proactive analysis applied to CT, whereas the second is a reactive analysis performed following a sentinel event triggered by a CT study allocated to the wrong patient in the RIS-PACS system.


Modification of gene expression and soluble factor secretion in the lateral ventricle choroid plexus: Analysis of the impacts on the neocortical development.
The choroid plexus (ChP) is the center of soluble factor secretion into the cerebrospinal fluid in the central nervous system. It is known that various signaling factors secreted from the ChP are involved in the regulation of brain development and homeostasis. Intriguingly, the size of the ChP was prominently expanded in the brains of primates, including humans, suggesting that the expansion of the ChP contributed to mammalian brain evolution, leading to the acquisition of higher intelligence and cognitive functions. To address this hypothesis, we established transgenic (Tg) systems using regulatory elements that direct expression of candidate genes in the ChP. Overexpression of sonic hedgehog (Shh) in the developing ChP led to the expansion of the ChP with greater arborization. Shh produced in the ChP caused an increase in neural stem cells (NSCs) in the neocortical region, leading to the expansion of ventricles, ventricular zone and neocortical surface area, and neocortical surface folding. These findings suggest that the activation of Shh signaling via its enhanced secretion from the developing ChP contributed to the evolution of the neocortex. Furthermore, we found that Shh produced in the ChP enhanced NSC proliferation in the postnatal Tg brain, demonstrating that our Tg system can be used to estimate the effects of candidate factors secreted from the ChP on various aspects of brain morphogenesis and functions.


Key elements of a highly efficient intracytoplasmic sperm injection technique: Ca2+ fluxes and oocyte cytoplasmic dislocation.
To analyze the mechanism by which modifications of the intracytoplasmic sperm injection (ICSI) technique influence success rates. Prospective clinical study supplemented with an experimental analysis of Ca2+ fluxes provoked by the injection procedure. Private hospital and public research center. Patients treated by IVF and ICSI. Intracytoplasmic sperm injection. Fertilization and pregnancy rates and intracellular free Ca2+ concentration. The inclusion of vigorous aspiration of oocyte cytoplasm improved outcomes of ICSI. In a series of 100 consecutive cases treated with this technique, the fertilization and pregnancy rates were 87% of total metaphase II oocytes injected and 52% of total treatment cycles, respectively. Enhanced Ca2+ influx into the injected oocytes and dislocation of the oocyte cytoplasm, including the development of a focus of persistent Ca2+ discharge around the injected sperm head, were the main characteristics of this highly successful technique. Vigorous aspiration of oocyte cytoplasm may facilitate fertilization after ICSI by increasing the oocyte Ca2+ load at the time of injection, by establishing a more intimate contact of the injected sperm head with oocyte intracellular Ca2+ stores, or by a conjunction of these mechanisms.


Triple-negative breast cancer: early assessment with 18F-FDG PET/CT during neoadjuvant chemotherapy identifies patients who are unlikely to achieve a pathologic complete response and are at a high risk of early relapse.
Triple-negative breast cancer, an aggressive subtype, represents 15% of invasive breast tumors. This prospective study investigated whether early changes in (18)F-FDG tumor uptake during neoadjuvant chemotherapy (NAC) can predict outcomes. Twenty (M0) patients underwent (18)F-FDG PET/CT at baseline and after the second cycle. NAC was continued irrespective of PET results. At surgery, 6 patients had a pathologic complete response, whereas 14 had residual tumor. Four patients showed early relapse (in the 2 y after surgery). There were 11 metabolic responders and 9 nonresponders using a 42% decrease in maximum standardized uptake value as a cutoff. In nonresponding patients, the risk of residual tumor at surgery was 100% (vs. 45% in responders; P = 0.014), and the risk of early relapse was 44% (vs. 0%; P = 0.024). A less than 42% decrease in (18)F-FDG uptake at 2 cycles means residual tumor at the end of NAC and a high risk of early relapse.


Effect of stress on oral fentanyl consumption in rats in an operant self-administration paradigm.
The effect of intermittent footshock stress (0.8 mA; 0.2 s on; 40 s off on the average; for 10 min/day) on oral fentanyl (50 or 75 micrograms/ml) self-administration (SA) in operant chambers was examined in male rats. In Experiment 1, after 1 month of initiation of the fentanyl SA by partial water deprivation, animals were tested for lever-pressing for fentanyl (75 micrograms/ml) under fixed-ratio-4 (FR-4) and progressive-ratio (PR) schedules of reinforcement for 30 min/day in operant chambers. Exposure to footshock stress increased fentanyl SA under the FR-4 and PR schedules compared with a nonstress condition. When water was substituted for the drug, the operant behavior persisted before extinction. In Experiment 2, different rats were tested for lever-pressing for fentanyl (50 micrograms/ml) under FR-6 and PR schedules. This experiment further assessed the role of taste in the stress-induced fentanyl SA and examined the effect of increasing the schedule requirements (i.e., FR-3, 6, and 12) on lever-pressing for fentanyl. Exposure to footshock stress increased lever-pressing for oral fentanyl SA under the FR schedules of reinforcement. When a quinine solution (30 micrograms/ml), matched for bitter taste with the fentanyl solution, was substituted for the drug solution, an extinction of the drug-reinforced behavior occurred, indicating that the stress-induced oral fentanyl SA is not related to stress-induced changes in taste sensitivity. In both experiments, no significant stress effects were observed for water consumption in home cage and lever-pressing on the nonoperative lever.


Microsomal conjugation and oxidation of bilirubin.
Bilirubin diglucuronide and bilirubin monoglucuronide are formed on incubation of microsomal preparations from rat liver with bilirubin and UDPglucuronate. Microsomal diglucuronide formation is a two-step reaction: first monoglucuronide is formed and this is subsequently converted to diglucuronide. Both steps require UDPglucuronate and have a similar pH optimum at pH 7.8. Albumin inhibits the conversion of monoto diglucuronide. Factors favouring diglucuronide formation are: (a) low bilirubin concentration; (b) relatively high UDPglucuronate concentration; (c) complete removal of UDPglucuronyltransferase latency. For the latter, trypsin-treatment appeared superior over digitonin or UDP-N-acetylglucosamine. Trypsin-treatment had to be done under strictly anaerobic conditions. If trypsin treatment was done under aerobic conditions, reactive molecules were formed which initiated the rapid oxidation of bilirubin and its glucuronides. Microsomal oxidation of bilirubin and glucuronides also occurred in untreated and digitonin-treated microsomes and was stimulated by NADPH and by the cytochrome P-450 inhibitor, metyrapone. This suggests that lipid peroxides act as initiators of bilirubin oxidation. Indirect evidence was found that trypsin inactivates nucleotide pyrophosphatase. This is an active UDPglucuronate-consuming enzyme in microsomal preparations which must be inactivated before meaningful kinetic studies can be done. With trypsin-treated microsomal preparations the Vmax for bilirubin monoglucuronide formation was 1.7 X 10(-9) mol . mg protein-1 . min-1 and KUDPglucuronatem 43 X 10(-6) M. For bilirubin diglucoronide formation the apparent Vmax was 0.7 X 10(-9) mol . mg protein-1 . min-1 and the apparent KUDPglucuronate m 1.0 X 10(-3) M.