Phosphorylation regulates the interaction and complex formation between wt p53 protein and PARP-1.
We recently characterized the interaction between poly(ADP-ribose) polymerase-1 (PARP-1) and the product of the tumor suppressor gene p53. We investigated which domains of human PARP-1 and of human wild-type (wt) p53 were involved in this protein-protein interaction. We generated baculoviral constructs encoding full length or distinct functional domains of both proteins. Full length PARP-1 was simultaneously coexpressed in insect cells with full length wt p53 protein or its distinct truncated fragments and vice versa. Reciprocal immunoprecipitation of Sf9 cell lysates revealed that the central and carboxy-terminal fragments of p53 were sufficient to confer binding to PARP-1, whereas the amino-terminal part harboring the transactivation functional domain was dispensable. On the other hand, the amino-terminal and central fragments of PARP-1 were necessary for complex formation with p53 protein. As the most important features of p53 protein are regulated by phosphorylation, we addressed the question of whether its phosphorylation is essential for binding between the two proteins. Baculovirally expressed wt p53 was post-translationally modified. At least six distinct p53 isomeres were resolved by immunoblotting following two-dimensional separation of baculovirally expressed wt p53 protein. Using specific phospho-serine antibodies, we identified phosphorylation of baculovirally expressed p53 protein at five distinct sites. To define the role of p53 phosphorylation, pull-down assays using untreated and dephosphorylated p53 protein were performed. Dephosphorylated p53 failed to bind PARP-1 indicating that complex formation between both proteins is regulated by phosphorylation of p53. The marked phosphorylation of p53 at Ser392 observed in unstressed cells suggests that the phosphorylated carboxy-terminal part of p53 undergoes complex formation with PARP-1 resulting in masking of the NES and thereby preventing its export. The functional significance of the interaction between both proteins was investigated at two different conditions: inactivation of PARP-1 and overexpression of PARP-1. Our results unequivocally show that the presence of PARP-1 regulates the basal expression of wt p53 in unstressed cells.


Branched-chain amino acids attenuate early kidney injury in diabetic rats.
Diabetic nephropathy (DN) is the most severe diabetic microvascular complication. The pathogenesis of diabetic nephropathy is complex, and oxidative stress plays an important role in the development of diabetic nephropathy. Elevated reactive oxygen species (ROS) levels activate various signaling pathways and influence the activities of transforming growth factor-β (TGF-β) and matrix metalloproteinase-9 (MMP-9), which contributes to glomerular hypertrophy. Branched-chain amino acids (BCAAs) are widely used in clinical treatment, and BCAAs can reduce the oxidative stress associated with the diabetic pancreas and some liver diseases. Thus, the aim of the present study was to determine whether BCAAs could attenuate oxidative stress in the kidneys of streptozotocin (STZ)-induced diabetic rats to prevent early diabetic kidney injury. Male Wistar rats were fed for two weeks with a normal chow diet or a high-fat diet in which 40% of calories were derived from fat. After this two-week period, the mice fed normal chow were injected with vehicle, while the high-fat diet group was injected intraperitoneally (i.p.) with 40 mg/kg STZ. The STZ-treated group was randomly divided into four subgroups that were treated with different doses of BCAAs or vehicle for two months by oral gavage. Plasma glucose, plasma creatinine, urinary protein and JNK, TGF-β, and MMP-9 mRNA and protein expression levels were measured in the rats. The ROS levels and proteinuria in the STZ-induced diabetic rats were significantly higher than those in the control groups. Moreover, early kidney injury occurred in the STZ-induced diabetic rats. However, BCAAs treatment decreased ROS levels, proteinuria and kidney injury. Moreover, JNK, TGF-β and MMP-9 mRNA and protein levels were significantly increased in the diabetic rats when compared with the control rats, and BCAAs treatment reversed these changes. Our results suggest that BCAAs counter oxidative stress in the kidneys of diabetic rats and alleviate diabetic kidney injury via the JNK/TGF-β/MMP-9 pathway.


FITC-induced murine pulmonary inflammation: CC10 up-regulation and concurrent Shh expression.
We describe an immunohistochemical study of the acute and chronic effects of fluorescein isothiocyanate (FITC) on Sonic hedgehog (Shh) expression and Clara cell secretory protein (CC10) up-regulation in murine lung. FITC was dissolved in PBS and instilled non-surgically into adult mouse lungs via the trachea. During the acute phase (120h) of the FITC response, CC10 staining within Clara cells increased markedly but the protein did not leak into the tissue spaces or the airways, and no fibrosis was apparent. An immune response was evident, characterised by infiltrating T and B lymphocytes. There was no concomitant expression of Shh. During the chronic phase (6 months post-instillation), significant tissue degeneration was observed in the airways. There was moderate to severe fibrosis in the lung fields that stained positively for FITC and significant inflammatory cell infiltrate was observed. Shh was expressed, and CC10 showed multiple sites of diffuse staining consistent with release from Clara cells into alveolar air spaces. PBS controls showed no fibrosis after 6 months, but there was positive Shh staining below the airway epithelia and minimal extracellular CC10 staining. The results may throw some light on the role of CC10 in pulmonary inflammation. The relationship of Shh expression and CC10 leakage to lung damage and repair is discussed.


Persistence of Tuber melanosporum in truffle orchards in North Carolina, USA.
A survey was conducted to determine the persistence of mycorrhization by Tuber melanosporum in truffle orchards established with European and American species of oak and common hazel trees in North Carolina. The trees had reportedly been inoculated and colonized by T. melanosporum prior to planting. Root samples were collected from 95 trees among seven orchards in 2015 and roots were analyzed by morphology and quantitative PCR. Samples that tested negative for T. melanosporum or where ectomycorrhizal morphology was not observed were analyzed by sequencing to identify the mycorrhizal fungal symbiont present. The presence of T. melanosporum was detected in all seven orchards. In six orchards, T. melanosporum was detected on all trees, but in only two of fifteen trees in one orchard. Other species of Tuber including T. brennemanii, T. canaliculatum, and T. lyonii, species of Scleroderma, and members of the Pezizales were also detected by sequence analysis. Sporocarps of T. aestivum and T. brumale were found in 2017 and 2018 in separate orchards in North Carolina after the survey was conducted. Overall, results indicate that T. melanosporum has persisted in truffle orchards sampled in North Carolina. Indigenous and contaminating fungal species, including Tuber species, were also detected and present a challenge to the truffle industry in North Carolina.


Studies concerning the viability of the preserved kidney with perfusates other than plasma.
Based on previous data, this research deals with the study of cellular ultrastructure of renal tissue (cortical and medullary) in conditions of preservation through a continuous hypothermic pulsatile perfusion, using a solution that substitutes plasma as the perfusate. This experiment was done on isolated dog kidneys perfused with a specialized perfusion machine. The results clearly show that with this method of renal preservation, no major lesions or irreversible modifications of the nephrons occur within 12 hours, offering the organ posttransplanting compatibility.


Viral Titer Quantification of West Nile Virus by Immunostaining Plaque Assay.
Immunostained plaque assay based on the specific antibody binding to viral antigen enables the detection and titration of virus infectivity, especially for viruses that could not form plaques using the classical crystal violet or neutral red staining methods. Here we describe the application of this method to quantify viral titers of wild-type West Nile virus (WNV-WT) and replication-defective WNV-ΔNS1 virus.


Cell contraction caused by microtubule disruption is accompanied by shape changes and an increased elasticity measured by scanning acoustic microscopy.
The state of crosslinking of microfilaments and the state of myosin-driven contraction are the main determinants of the mechanical properties of the cell cortex underneath the membrane, which is significant for the mechanism of shaping cells. Therefore, any change in the contractile state of the actomyosin network would alter the mechanical properties and finally result in shape changes. The relationship of microtubules to the mechanical properties of cells is still obscure. The main problem arises because disruption of microtubules enhances acto-myosin-driven contraction. This reaction and its impact on cell shape and elasticity have been investigated in single XTH-2 cells. Microtubule disruption was induced by colcemid, a polymerization inhibitor. The reaction was biphasic: a change in cell shape from a fried egg shape to a convex surface topography was accompanied by an increase in elastic stiffness of the cytoplasm, measured as longitudinal sound velocity revealed by scanning acoustic microscope. Elasticity increases in the cell periphery and reaches its peak after 30 min. Subsequently while the cytoplasm retracts from the periphery, longitudinal sound velocity (elasticity) decreases. Simultaneously, a two- to threefold increase of F-actin and alignment of stress fibers from the cell center to cell-cell junctions in dense cultures are induced, supposedly a consequence of the increased tension.


Stress and health.
The impact of stress on physical functioning (endocrine, gastrointestinal, immune, and cardiovascular systems) is reviewed. The effect of stress on psychiatric functioning and health behaviors also is discussed. The importance of stress screening in primary care is emphasized, and several methods of stress reduction (including exercise, cognitive-behavioral therapy, and mindfulness-based stress reduction) appropriate to primary care settings are described.


Evolution of equine infectious anaemia in naturally infected mules with different serological reactivity patterns prior and after immune suppression.
Information on equine infectious anaemia (EIA) in mules, including those with an equivocal reaction in agar gel immunodiffusion test (AGIDT), is scarce. For this, a study was conducted to evaluate the clinical, viral loads and pathological findings of two groups of naturally infected asymptomatic mules, respectively with a negative/equivocal and positive AGIDT reactivity, which were subjected to pharmacological immune suppression (IS). A non-infected control was included in the study that remained negative during the observation period. Throughout the whole study, even repeated episodes of recrudescence of EIA were observed in 9 infected mules, independently from their AGIDT reactivity. These events were generally characterised by mild, transient alterations, typical of the EIA acute form represented by hyperthermia and thrombocytopenia, in concomitance with viral RNA (vRNA) peaks that were higher in the Post-IS period, reaching values similar to those of horses during the clinical acute phase of EIA. Total tissue viral nucleic acid loads were greatest in animals with the major vRNA activity and in particular in those with negative/equivocal AGIDT reactivity. vRNA replication levels were around 10-1000 times lower than those reported in horses, with the animals still presenting typical alterations of EIA reactivation. Macroscopic lesions were absent in all the infected animals while histological alterations were characterised by lymphomonocyte infiltrates and moderate hemosiderosis in the cytoplasm of macrophages. On the basis of the above results, even mules with an equivocal/negative AGIDT reaction may act as EIAV reservoirs. Moreover, such animals could escape detection due to the low AGIDT sensitivity and therefore contribute to the maintenance and spread of the infection.


Capturing the activity factor: impact on volume.
In addition to Patient Classification System's information, nurse managers can use activity tools to develop and justify budget needs. A basic accounting-type workflow analysis format, which goes beyond the "Midnight Census," accurately details a unit's patient volume and productive hours.


Quantitative structure-activity relationships of estrogenic steroids substituted at C14, C15.
The uterotropic activity of thirty 3-methoxyestradiol derivatives is measured and discussed on the basis of X-ray crystallographic results and quantitative structure-activity relationship analyses involving hydrophobic substituent constants pi and f as well as steric parameters Pr and L. In addition, estrogenicity is compared to data of interceptive activity and receptor binding affinity. All the biological data exhibit a high degree of intercorrelation. 17 beta-Hydroxysteroids having 14 alpha configuration reveal a generally better capability of high-affinity binding than those being 14 beta configurated. Between the uterotropic activity and the hydrophobicity of C14, C15 substituents, statistically significant correlations are found which suggest a close contact between the steroidal D-ring subsite and the receptor protein (e.g. for 14 alpha steroids: log UDD = -0.996 pi -0.392; n = 9, r = -0.943, s = 0.235, t = -7.5, alpha less than 0.001). The hydrophobic nature of both 14 alpha and 14 beta medium-sized substituents employed is shown by QSAR regressions to exert a stronger influence than steric effects. Furthermore, there are indications to additional hydrogen bonding and steric repulsion phenomena. As to the receptor-binding models discussed in the literature, it is concluded that the receptor protein has a high conformational flexibility to accommodate very different drug structures all having the common phenolic ring A. But, if an appropriate spacing of steroidal key atoms is recognized by the receptor and, consequently, the steroid-receptor complex is formed, the binding is complemented by hydrophobic interactions also in the D-ring region.


Objective assessment of intensive targeted treatment for solar lentigines using intense pulsed light with wavelengths between 500 and 635 nm.
Solar lentigines are commonly found in sun-exposed areas of the body including hands, neck, or face. This study evaluates the efficacy of an intense pulsed light (IPL) device, with wavelengths between 500 and 635 nm and delivered with a targeted tip, for the treatment of solar lentigines on Japanese skin. Forty Japanese patients with solar lentigines received one IPL treatment with a targeted treatment tip that emits wavelengths between 500 and 635 nm and contact cooling. Pulses were delivered through a targeted tip to each lentigo until mild swelling and a gray color were observed. Digital photographs and gray level histogram values were taken pre- and post-treatment, and patient assessments were recorded post-treatment. Significant improvement was observed for all patients in digital photographs and mean values of gray level histograms (P < 0.0001). Ninety percent of patients reported satisfaction with the improvement of the treatment area and convenience of the procedure. Complications were minor and transitory, consisting of a slight burning sensation and mild erythema which resolved within 5 hours of treatment. No serious adverse events were observed. A short-wavelength IPL, delivered with a targeted tip and contact cooling, offers a highly efficacious treatment for solar lentigines in Japanese skin with minimal downtime and complications.


Multi-tracer approach to understand nitrate contamination and groundwater-surface water interactions in the Mediterranean coastal area of Guerbes-Senhadja, Algeria.
Implementing sustainable groundwater resources management in coastal areas is challenging due to the negative impacts of anthropogenic stressors and various interactions between groundwater and surface water. This study focuses on nitrate contamination and transport via groundwater-surface water exchange in a Mediterranean coastal area (Guerbes-Senhadja region, Algeria) that is heavily affected by anthropogenic activities. A multi-tracer approach, integrating hydrogeochemical and isotopic tracers (δ2HH2O, δ18OH2O, 3H, δ15NNO3 and δ18ONO3), is combined with a Bayesian isotope mixing model (MixSIAR) to (i) elucidate the nitrate sources and their apportionments in water systems, and (ii) describe potential interactions between groundwater and surface water. Results from nitrate isotopic composition and the MixSIAR model show that nitrate concentrations mainly originate from sewage and manure sources. Nitrate derived from the sewage is attributed to urban and rural wastewater discharge, whereas nitrate derived from the manure is related to animal manure used to fertilise agricultural areas. High apportionments of nitrate-based atmospheric precipitation are identified in groundwater and surface water; a finding that is specific to this study. The multi-origin stresses combined with evidence of interactions between surface water and groundwater contribute to negatively impacting large parts of the study coastal area. The outcomes of this study are expected to contribute to sustainable management of coastal ecosystems by drawing more attention towards groundwater use and protection. Furthermore, this study may improve scientists' ability to predict the behavior of anthropogenically impacted coastal ecosystems and help decision-makers elsewhere to prepare suitable environmental strategies for other coastal ecosystems currently undergoing an early stage of groundwater resources deterioration.


Carcinoma of the prostate clinically and radiologically simulating malignant lymphoma.
A 65-year-old man presented with supraclavicular, mediastinal, and retroperitoneal lymphadenopathy clinically thought to be due to malignant lymphoma. Biopsy of a supraclavicular lymph node revealed metastatic adenocarcinoma positive for prostatic-specific antigen. This site of the primary tumor was confirmed by needle biopsy of the prostate gland. The tumor regressed dramatically following treatment with estramustine phosphate.


DNA-protein crosslink repair.
DNA-protein crosslinks (DPCs) are highly toxic DNA adducts, but whether dedicated DPC-repair mechanisms exist was until recently unknown. This has changed with discoveries made in yeast and Xenopus laevis that revealed a protease-based DNA-repair pathway specific for DPCs. Importantly, mutations in the gene encoding the putative human homologue of a yeast DPC protease cause a human premature ageing and cancer predisposition syndrome. Thus, DPC repair is a previously overlooked genome-maintenance mechanism that may be essential for tumour suppression.


Canadian inter-laboratory organically bound tritium (OBT) analysis exercise.
Tritium emissions are one of the main concerns with regard to CANDU reactors and Canadian nuclear facilities. After the Fukushima accident, the Canadian Nuclear Regulatory Commission suggested that models used in risk assessment of Canadian nuclear facilities be firmly based on measured data. Procedures for measurement of tritium as HTO (tritiated water) are well established, but there are no standard methods and certified reference materials for measurement of organically bound tritium (OBT) in environmental samples. This paper describes and discusses an inter-laboratory comparison study in which OBT in three different dried environmental samples (fish, Swiss chard and potato) was measured to evaluate OBT analysis methods currently used by CANDU Owners Group (COG) members. The variations in the measured OBT activity concentrations between all laboratories were less than approximately 20%, with a total uncertainty between 11 and 17%. Based on the results using the dried samples, the current OBT analysis methods for combustion, distillation and counting are generally acceptable. However, a complete consensus OBT analysis methodology with respect to freeze-drying, rinsing, combustion, distillation and counting is required. Also, an exercise using low-level tritium samples (less than 100 Bq/L or 20 Bq/kg-fresh) would be useful in the near future to more fully evaluate the current OBT analysis methods.


Mass spectrometry in gene therapy: Challenges and opportunities for AAV analysis.
The characterization of adeno-associated virus (AAV)-based gene therapy products represents significant challenges owing to their extremely large molecular sizes, structural complexity and heterogeneity, and limited sample amounts. Mass spectrometry (MS) is one of the key analytical tools that can overcome these challenges and serve as an important technique for the analysis of multiple attributes. In this review, the current methodologies and emerging trends in MS analysis of AAV gene therapy products are presented, highlighting their advantages and unique capabilities in addressing key issues encountered in intact AAV vector analysis, capsid viral protein characterization and impurity analysis.


Calcium-binding proteins in rat skin.
Skin Ca2+-binding protein (SCaBP) was reported to be distinct from the Ca2+-binding parvalbumin (PV), however, more recently its amino acid sequence was shown to be identical to PV. We purified a protein (Mr 12,000; pI4.5) from isolated epidermis (free of other cell layers) of adult rats and whole skin (containing no PV) of newborn rats. This protein is referred to as epidermal protein (EP-12), distinct from PV in its hydrophobicity, amino acid composition and immunological properties. Previously isolated SCaBP was shown to be a mixture of EP-12 and PV. The localization and possible functions of EP-12 and of PV in skin of adult and newborn rat are discussed.


Genotoxicity testing of the herbicide trifluralin and its commercial formulation Treflan using the piscine micronucleus test.
In this study, the genotoxic effects of a widely used herbicide, trifluralin, and its commercial formulation, Treflan, were evaluated using the micronucleus test in a commercially important fish species, Oreochromis niloticus (Nile Tilapia). Fish were exposed to 1, 5, and 10 microg/L doses of trifluralin and Treflan for 3, 6, and 9 days under laboratory conditions. Ethylmethanesulfonate, at a single dose of 10 mg/L, was used as positive control. Micronuclei were evaluated on the peripheral erythrocytes. Both Treflan and trifluralin treatments significantly increased the micronucleus frequencies in peripheral erythrocytes of O. niloticus. Furthermore, the genotoxicity of the active ingredient, trifluralin, was observed to be higher than that of the commercial formulation Treflan. Our results indicate that herbicide trifluralin has genotoxic potential in fish.


The multifunctional Ca²⁺/calmodulin-dependent kinase IIδ (CaMKIIδ) regulates arteriogenesis in a mouse model of flow-mediated remodeling.
Sustained hemodynamic stress mediated by high blood flow promotes arteriogenesis, the outward remodeling of existing arteries. Here, we examined whether Ca²⁺/calmodulin-dependent kinase II (CaMKII) regulates arteriogenesis. Ligation of the left common carotid led to an increase in vessel diameter and perimeter of internal and external elastic lamina in the contralateral, right common carotid. Deletion of CaMKIIδ (CaMKIIδ-/-) abolished this outward remodeling. Carotid ligation increased CaMKII expression and was associated with oxidative activation of CaMKII in the adventitia and endothelium. Remodeling was abrogated in a knock-in model in which oxidative activation of CaMKII is abolished. Early after ligation, matrix metalloproteinase 9 (MMP9) was robustly expressed in the adventitia of right carotid arteries of WT but not CaMKIIδ-/- mice. MMP9 mainly colocalized with adventitial macrophages. In contrast, we did not observe an effect of CaMKIIδ deficiency on other proposed mediators of arteriogenesis such as expression of adhesion molecules or smooth muscle proliferation. Transplantation of WT bone marrow into CaMKIIδ-/- mice normalized flow-mediated remodeling. CaMKIIδ is activated by oxidation under high blood flow conditions and is required for flow-mediated remodeling through a mechanism that includes increased MMP9 expression in bone marrow-derived cells invading the arterial wall.


Physiotherapy methods of relieving pain.
Management of pain in the person with arthritis requires interdisciplinary team work with the patient being the final manager. It is important that any health care provider perceive the patient as a person who happens to have arthritis--not as 'an "arthritic".' Defining a person by one's disease process is dehumanizing. The patient has the same aspirations as anyone who is ablebodied--to be free from disease. While the patient may know that a cure is not imminent, there is still the hope for one. Therefore, as the patient comes for physiotherapy, there may be a hidden wish that the moist packs, TENS, or therapeutic pool will be curative. It is important that the patient understand that no equipment in the physiotherapy department has curative powers. This will help avoid unnecessary dependency behaviours on the part of the patient. Careful instruction and supervision of the patient by the physiotherapist, in concert with reinforcement from the physician, can prepare the patient to apply heat, cold, or a variety of treatments at home. Although the patient is given the responsibility for this part of his care, periodic follow-up and reassessment should be completed to determine changes in his physiological, psychological, and functional status. Physiotherapists who have a clear understanding of the physical treatment of pain associated with the rheumatic diseases can be a valuable asset to medical care.


Genetic variants of the kynurenine-3-monooxygenase and postpartum depressive symptoms after cesarean section in Chinese women.
New conceptualizations of depression have emphasized the role of the kynurenine pathway (KP) in the pathogenesis of postpartum depressive symptoms (PDS). Kynurenine 3-monooxygenase (KMO) is a rate-limiting enzyme of the KP, where it catalyzes the conversion of kynurenine (KYN) to 3-hydroxykynurenine (3-HK). Previous work indicates that KMO is closely linked to the pathophysiology of depressive disorders. The purpose of this study is to investigate whether variations in the KMO gene affect PDS development after cesarean section. A total of 710 Chinese women receiving cesarean section were enrolled in this study. PDS was determined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥13. Subsequently, 24 women with PDS and 48 matched women without PDS were randomly selected for investigation of perinatal serum concentrations of KYN, 3-HK and the 3-HK/KYN ratio. The 3-HK/KYN ratio indicates the activity of KMO. In addition, 6 single nucleotide polymorphisms of the KMO gene were examined. Following this genotyping, 36 puerperant women carrying the KMO rs1053230 AG genotype and 72 matched puerperant women carrying the KMO rs1053230 GG genotype were selected for comparisons of KYN, 3-HK and 3-HK/KYN ratio levels. The results show the incidence of PDS in the Chinese population to be 7.3%, with PDS characterized by increased serum 3-HK concentration and 3-HK/KYN ratio, versus matched postpartum women without PDS (P<0.05). Furthermore, polymorphisms of KMO rs1053230 are significantly associated with the incidence of PDS (P<0.05). The serum concentrations of 3-HK and the 3-HK/KYN ratio in postpartum women carrying the KMO rs1053230 AG genotype are significantly higher than those in matched postpartum women carrying the KMO rs1053230 GG genotype. The presented data highlight the contribution of alterations in the KP to the pathogenesis of postpartum depression. Heightened KMO activity, including as arising from KMO rs1053230 G/A genetic variations, are indicated as one possible mechanism driving the biological underpinnings of PDS.


Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study.
To investigate whether measles, mumps, and rubella (MMR) vaccination is associated with bowel problems and developmental regression in children with autism, looking for evidence of a "new variant" form of autism. Population study with case note review linked to independently recorded vaccine data. Five health districts in north east London. 278 children with core autism and 195 with atypical autism, mainly identified from computerised disability registers and born between 1979 and 1998. Recorded bowel problems lasting at least three months, age of reported regression of the child's development where it was a feature, and relation of these to MMR vaccination. The proportion of children with developmental regression (25% overall) or bowel symptoms (17%) did not change significantly (P value for trend 0.50 and 0.47, respectively) during the 20 years from 1979, a period which included the introduction of MMR vaccination in October 1988. No significant difference was found in rates of bowel problems or regression in children who received the MMR vaccine before their parents became concerned about their development (where MMR might have caused or triggered the autism with regression or bowel problem), compared with those who received it only after such concern and those who had not received the MMR vaccine. A possible association between non-specific bowel problems and regression in children with autism was seen but this was unrelated to MMR vaccination. These findings provide no support for an MMR associated "new variant" form of autism with developmental regression and bowel problems, and further evidence against involvement of MMR vaccine in the initiation of autism.


Tales from the ACFI: Dementia in residential aged care.
Provide an overview of how care needs in permanent residential aged care differ by dementia status. On entry into permanent residential aged care, people's care needs are assessed on the Aged Care Funding Instrument (ACFI). ACFI also captures health conditions that are considered to affect the cost of people's care, such as dementia. Data were compared between 2009 and 2015. Assessed care needs have increased regardless of dementia status. However, compared with people without dementia, people with dementia were more likely to be rated 'high' in each of the three care need domains. In addition, people with dementia were more likely to require some assistance in specific areas that underlie these broad domains, such as nutrition, continence and cognition. Dementia is associated with increased complexity in assessed care needs in permanent residential aged care.


Congenital heart disease does not entail an increased risk for severe COVID-19.
To analyse the risk of developing serious disease or death due to COVID-19 among patients who underwent heart surgery during childhood. A retrospective combined register and patient file study. We identified all individuals who had undergone surgery for congenital heart disease in childhood between 1994 and 2019 in our Local Surgical Register that covers half of the Swedish population. This effort was cross-tabulated with the diagnosis of COVID-19 entered in the National Register of Diagnoses in Sweden from 1 March 2020 to 1 March 2021. Severe disease was defined as treatment at an intensive care unit (ICU). We identified 3950 individuals, and the median age at follow-up was 16 years (1-44). A total of 32 patients were diagnosed with COVID-19. Five of them were hospitalised for more than 2 days (5-32 days). Two adults required treatment at an ICU; both had additional comorbidity and one died. The corresponding number of ICU stays for this age range in Sweden was 2020 approximately 0.13/1000 person-years, reported from The Swedish Intensive Care Registry. There was no increased rate of severe COVID-19 among individuals who had undergone surgery for congenital heart disease in childhood. Additional comorbidity is related to outcome.


4-Aminoquinoline quinolizidinyl- and quinolizidinylalkyl-derivatives with antimalarial activity.
A set of quinolizidinyl and quinolizidinylalkyl derivatives of 4-amino-7-chloroquinoline and of 9-amino-6-chloro-2-methoxyacridine were prepared and tested in vitro against CQ-sensitive (D-10) and CQ-resistant (W-2) strains of Plasmodium falciparum. All compounds but one exerted significant antimalarial activity. Some of the quinolizidine derivatives were from 5 to 10 times more active than chloroquine on the CQ-resistant strain. No toxicity against mammalian cells was observed.


Moderate and severe periodontitis are positively associated with metabolic syndrome.
This study investigated the association between periodontitis severity (exposure) and metabolic syndrome (MetS - outcome), using two criteria for diagnosis of the outcome, since this relationship remains unexplored. A case-control study was conducted with 870 individuals: 408 with first MetS diagnosis (cases) and 462 without MetS (controls). Participants' general information was obtained using a questionnaire and laboratory data was collected from medical records. Periodontitis severity criteria followed the Center for Disease Control and Prevention: none, mild, moderate, and severe. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by logistic regression analysis. Findings showed a positive association between moderate and severe periodontitis and MetS: ORadjusted = 1.64 (95% CI: 1.01 to 2.68) and ORadjusted = 1.94 (95% CI: 1.19 to 3.16), respectively, after adjustment for age, sex, schooling level, smoking habit, and cardiovascular disease. The adjusted measurements showed that among individuals with moderate or severe periodontitis, the probability of having MetS was around two times greater than among those without periodontitis, and that the chance was greater among participants with severe periodontitis than those with moderate periodontitis. An association between the severity of periodontal status and MetS was found, suggesting a possible relationship between the two diseases. MetS influences the etiology of cardiovascular diseases, one of the leading causes of mortality worldwide. The findings suggest that the greater the severity of periodontitis, the greater is the association magnitude with MetS. The health professional needs to recognize that the importance of periodontal disease may play in MetS.


T cell triggering by lectins. I. Requirements for interleukin 2 production; lectin concentration determines the accessory cell dependency.
The requirements for lectin-induced interleukin 2 (IL2) production by human T cells have been investigated. With two different types of T cells, the Jurkat T cell lymphoma and highly purified HLA class II- peripheral T cells, the amount of IL2 produced was strongly dependent on the lectin concentration used. Addition of accessory cells caused a shift in the dose-response curve, resulting in strongly enhanced IL2 production at low concentrations. Thus, the (absolute) accessory cell dependency for T cells to produce IL2 is defined by experimental conditions. Only at lectin concentrations that were found to be optimal in the presence of accessory cells, removal of these cells abrogates IL2 production. Furthermore, after depletion of monocytes IL 2 production by peripheral T cells became almost completely dependent on the presence of thiols in the culture medium. In contrast, the IL2 production by the Jurkat line was not influenced by addition of thiols. The Jurkat model was used to study the nature of accessory cell because this cell line does not show any reactivity to allogeneic cells. Various myeloid and B lymphoid cell lines were tested as accessory cells. The capacity to function as accessory cell was not related to the monocytic origin of the cell. B cell lines were far more effective than monocytes, as two HLA class II- monocytic cell lines were not active. Even after HLA class II determinants were induced on these cells by incubation with an interferon-gamma-containing conditioned medium, they failed to act as as accessory cells. These experiments question the importance of HLA class II molecules and monokines, such as IL1, for lectin-induced IL2 production.


Experimental studies on morphological changes of microcirculation of DMN-induced liver cirrhosis after normothermic ischemia with charge-coupled device microscope.
The purpose of the present experiment was to find indices for intraoperative ischemic-reperfusion injury in the cirrhotic liver. One percent dimethylnitrosamine (DMN) was administered intraperitoneally to liver cirrhosis (LC) groups of Wister rats on three consecutive days of each week for a period of four weeks. The rats were divided into a N60 group with 60 minute ischemia in normal livers, a LC60 group with 60 minute ischemia in cirrhotic livers, and a LC30 group with 30 minute ischemia in cirrhotic livers. Digital videotapes recorded with a pencil lens-probe charge-coupled device (CCD) microscope were analyzed with NIH Image software. In zone 3, the sinusoid diameter (SD) was measured and the volume fraction (Vv) of zone 3 was calculated in preischemia and after 10, 20, 30, and 60 min of reperfusion. At the same time, bile flow was measured. The SD was significantly shorter in the cirrhotic liver groups than in the normal liver group at each point. The Vv after 60 min of reperfusion was significantly smaller in the LC60 group, with a survival rate of 0%, than in the LC30 group which had a survival rate of 67%. However, there was no significant difference in bile flow after 60 min of reperfusion in the LC30 and LC60 groups. Therefore, the Vv is suggested to be the better index for viability after ischemic-reperfusion. SD and Vv indicate microcirculatory differences and indices in the normal and cirrhotic livers in preischemia during reperfusion.


Acute flaccid myelitis outbreak through 2016-2018: A multicenter experience from Turkey.
We aim to describe the demographic characteristics, etiology, neurophysiology, imaging findings, treatment, prognosis, and prognostic factors of acute flaccid myelitis. The clinical data, laboratory test and, magnetic resonance imaging (MRI) results of pediatric patients diagnosed with acute flaccid myelitis according to the Centers for Disease Control criteria between August 1, 2016, and December 31, 2018, from 13 centers in Turkey were reviewed. Of the 34 cases identified, 31 were confirmed (91.2%). Eighteen patients (55.9%) were boys. The median patient age was 4 years (interquartile range 2.5-6.9 years). Most of the patients were admitted in 2018 (n = 27). A preceding history of a febrile illness was reported in all patients, with a median of 4 days (interquartile range 3-7 days) before symptom onset. Thirty-one patients had T2 hyperintensity on spinal MRI, and 18 patients had cerebrospinal fluid pleocytosis. The most common infectious agents were entero/rhinoviruses (n = 5) in respiratory specimens. All patients except one received immunotherapy either alone or in combination. Among 27 patients with follow-up data 24 had persistent weakness. Involvement of four limbs together with an abnormal brain MRI at onset were associated with a poor prognosis. The number of patients with acute flaccid myelitis increased since 2012, spiking with every 2-year interval, largely in the pediatric population. The median age decreases with every outbreak. Clinicians should be aware of the clinical picture for early collection of specimens and early start of rehabilitation programs. Further studies are needed to better characterize the etiology, pathogenesis, risk factors, and treatment of this rare condition.


Bisthioureas of pimelic acid and 4-methylsalicylic acid derivatives as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP): Synthesis and molecular docking studies.
Alkaline phosphatases (ALPs) are membrane bound metalloenzymes, distributed all over the body. Recent studies have revealed that by targeting ALPs can lead towards the treatment of many deadliest diseases including cardiac, cancerous and brain diseases. Thioureas and their derivatives are of considerable significance and are privileged scaffolds in medicinal chemistry. They show a wide range of pharmacological activities such as antibacterial, antiparasitic, anti-inflammatory and antioxidants etc. On the other hand, salicylic acid and its derivatives are known for its broad spectrum of activities. The work presented comprises of synthesis of N-acyl-N'-aryl substituted bisthioureas of pimelic acid (1-7) and 3,5-dimethyl pyrazole (11), 1-aroyl-3-aryl thiourea (12) and 1,3,4-oxadiazole (13) derivatives of 4-methyl salicylic acid. Structures of all the synthesized compounds were characterized by FT-IR and 1H NMR spectroscopic analysis. Synthesized compounds were evaluated for their alkaline phosphatases inhibition potential and exhibited high potency as well as selectivity towards h-TNAP and h-IAP. Compound 7 and 12 which were the bisthiourea derivative of pimmelic acid and thiourea derivative of 4-methyl salicylic acid, respectively, showed excellent selectivity against h-TNAP and h-IAP, respectively.


The social epidemiologic concept of fundamental cause.
The goal of research in social epidemiology is not simply conceptual clarification or theoretical understanding, but more importantly it is to contribute to, and enhance the health of populations (and so, too, the people who constitute those populations). Undoubtedly, understanding how various individual risk factors such as smoking and obesity affect the health of people does contribute to this goal. However, what is distinctive of much on-going work in social epidemiology is the view that analyses making use of individual-level variables is not enough. In the spirit of Durkheim and Weber, S. Leonard Syme makes this point by writing that just "as bad water and food may be harmful to our health, unhealthful forces in our society may be detrimental to our capacity to make choices and to form opinions" conducive to health and well-being. Advocates of upstream (distal) causes of adverse health outcomes propose to identify the most important of these "unhealthful forces" as the fundamental causes of adverse health outcomes. However, without a clear, theoretically precise and well-grounded understanding of the characteristics of fundamental causes, there is little hope in applying the statistical tools of the health sciences to hypotheses about fundamental causes, their outcomes, and policies intended to enhance the health of populations. This paper begins the process of characterizing the social epidemiological concept of fundamental cause in a theoretically respectable and robust way.


Pediatric mood and anxiety syndromes in primary care: who gets identified?.
To seek clues to the enhancement of primary care management by (i) Determining how often and in whom primary care clinicians in the United States, Puerto Rico, and Canada identify pediatric mood or anxiety syndromes; (ii) Determining which clinical and demographic features predict higher rates of identification; (iii) Describing assessment methods used. This report uses the database of the multi-site Child Behavior Study. This cross-sectional study involved 206 primary care practices in the United States, Puerto Rico, and Canada; 395 clinicians and 20,861 primary care attenders aged 4-15 years. Clinicians completed a visit questionnaire addressing presence and type of psychosocial problems and how assessed. Parents completed a questionnaire addressing family demographics, child symptoms (Pediatric Symptom Checklist) and functioning, and child service use. Clinicians identified psychosocial problems on 17.9% of visits, but mood or anxiety syndromes on only 3.3%, most commonly in children judged to have co-morbid behavioral syndromes, of whom the majority (66.7%) already had contact with specialized mental health. Neither parental concerns about mood and anxiety symptoms nor clinician familiarity with the patient were major predictors of identification. When making a diagnosis of a pure internalizing syndrome (i.e., without a co-morbid behavioral syndrome) clinicians rarely used standardized tools or school reports. Neither screening for nor diagnosis of mood and anxiety syndromes is a routine part of primary care of children and adolescents. Efforts to improve care must include practical, validated screening procedures to enhance assessment for mood and anxiety syndromes, particularly among children in whom primary care clinicians identify psychosocial problems.


Statistical Dimensioning of Nutrient Loading Reduction: LLR Assessment Tool for Lake Managers.
Implementation of the EU Water Framework Directive (WFD) has set a great challenge on river basin management planning. Assessing the water quality of lakes and coastal waters as well as setting the accepted nutrient loading levels requires appropriate decision supporting tools and models. Uncertainty that is inevitably related to the assessment results and rises from several sources calls for more precise quantification and consideration. In this study, we present a modeling tool, called lake load response (LLR), which can be used for statistical dimensioning of the nutrient loading reduction. LLR calculates the reduction that is needed to achieve good ecological status in a lake in terms of total nutrients and chlorophyll a (chl-a) concentration. We show that by combining an empirical nutrient retention model with a hierarchical chl-a model, the national lake monitoring data can be used more efficiently for predictions to a single lake. To estimate the uncertainties, we separate the residual variability and the parameter uncertainty of the modeling results with the probabilistic Bayesian modeling framework. LLR has been developed to answer the urgent need for fast and simple assessment methods, especially when implementing WFD at such an extensive scale as in Finland. With a case study for an eutrophic Finnish lake, we demonstrate how the model can be utilized to set the target loadings and to see how the uncertainties are quantified and how they are accumulating within the modeling chain.


Coupling of canine serotonin 5-HT(1B) and 5-HT(1D) receptor subtypes to the formation of inositol phosphates by dual interactions with endogenous G(i/o) and recombinant G(alpha15) proteins.
Molecular cloning and expression of canine (ca) serotonin 5-HT(1B) and ca 5-HT(1D) receptor subtypes showed that besides the lower binding affinity of ketanserin for the ca 5-HT(1D) receptor, the ligand binding profiles were similar to their human homologues. Site-directed mutagenesis studies suggest that a Gln(189) residue in the second extracellular loop of the ca 5-HT(1D) receptor may partially account for the lower binding affinity of ketanserin. The coupling of ca 5-HT(1B) and ca 5-HT(1D) receptor subtypes to the phospholipase C pathway was analyzed by measuring stimulation of inositol phosphate formation in COS-7 cells. Zolmitriptan potently stimulated (EC(50) = 4.9 nM) the inositol phosphate formation at ca 5-HT(1D) receptors in a fully pertussis toxin (PTX)-dependent manner, whereas only a weak PTX-resistant inositol phosphate response (26-29% at 10 microM zolmitriptan) could be detected for the ca 5-HT(1B) receptor at a similar expression level. In contrast, both ca 5-HT(1B) and ca 5-HT(1D) receptor subtypes yielded a similar maximal magnitude of inositol phosphate formation (300-340% at 10 microM zolmitriptan) upon co-expression with a mouse (m) G(alpha15) protein. PTX treatment and co-expression with a beta-adrenergic receptor kinase C-terminal polypeptide partially (20-46%) abolished the m G(alpha15) protein-dependent ca 5-HT(1B) and ca 5-HT(1D) receptor-mediated stimulation of inositol phosphate formation. This study suggests both 5-HT receptor subtypes can activate betagamma subunits of endogenous G(i/o) proteins besides their coupling to recombinant m G(alpha15) protein.


Altered intracellular calcium in fibroblasts from patients with cystic fibrosis and heterozygotes.
The importance of intracellular calcium (Ca) in secretion and transmembrane ion movement led us to study Ca in cells from patients with cystic fibrosis (CF) which is a lethal genetic exocrinopathy. Skin fibroblasts from patients with CF, obligate heterozygotes (HZ), and age- and sex-matched controls (C) were used in matched pair experiments measuring 45Ca exchange into and efflux from the cells over time. CF cell lines and HZ cell lines exhibit increased 45Ca exchange when compared with their respective controls (P less than 0.005). The magnitude of this difference (approximately 30%) is not reduced when cells are washed with lanthanum chloride after the exchange period. This difference is likely attributable to an altered capacity of one or more of the intracellular Ca sequestering organelles. Further evidence for this explanation was seen in 45Ca efflux experiments in which CF cells retained a higher percent of their initial 0-time 45Ca than did C cells late in the efflux period (P less than 0.05). The finding of an altered Ca pool size in both CF and particularly HZ cells suggests that altered Ca metabolism is related to the basic gene defect in CF.


Kinetic properties of Ca2+/calmodulin-dependent phosphodiesterase isoforms dictate intracellular cAMP dynamics in response to elevation of cytosolic Ca2+.
Multiply regulated adenylyl cyclases (AC) and phosphodiesterases (PDE) can yield complex intracellular cAMP signals. Ca2+-sensitive ACs have received far greater attention than the Ca2+/calmodulin-dependent PDE (PDE1) family in governing intracellular cAMP dynamics in response to changes in the cytosolic Ca2+ concentration ([Ca2+]i). Here, we have stably expressed two isoforms of PDE1, PDE1A2 and PDE1C4, in HEK-293 cells to determine whether they exert different impacts on cellular cAMP. Fractionation and imaging showed that both PDEs occurred mainly in the cytosol. However, PDE1A2 and PDE1C4 differed considerably in their ability to hydrolyze cAMP and in their susceptibility to inhibition by the non-selective PDE inhibitor, IBMX and the PDE1-selective inhibitor, MMX. PDE1A2 had an approximately 30-fold greater Km for cAMP than PDE1C4 and yet was more susceptible to inhibition by IBMX and MMX than was PDE1C4. These differences were mirrored in intact cells when thapsigargin-induced capacitative Ca2+ entry (CCE) activated the PDEs. Mirroring their kinetic properties, PDE1C4 was active at near basal cAMP levels, whereas PDE1A2 required agonist-triggered levels of cAMP, produced in response to stimulation of ACs. The effectiveness of IBMX and MMX to inhibit PDE1A2 and PDE1C4 in functional studies was inversely related to their respective affinities for cAMP. To assess the impact of the two isoforms on cAMP dynamics, real-time cAMP measurements were performed in single cells expressing the two PDE isoforms and a fluorescent Epac-1 cAMP biosensor, in response to CCE. These measurements showed that prostaglandin E1-mediated cAMP production was markedly attenuated in PDE1C4-expressing cells upon induction of CCE and cAMP hydrolysis occurred at a faster rate than in cells expressing PDE1A2 under similar conditions. These results prove that the kinetic properties of PDE isoforms play a major role in determining intracellular cAMP signals in response to physiological elevation of [Ca2+]i and thereby provide a rationale for the utility of diverse PDE1 species.


Regulation of hydrogen utilisation in Rhizobium japonicum by cyclic AMP.
Utilisation (uptake) of hydrogen gas by whole cells of Rhizobium japonicum was found to be influenced by the carbon source(s) present in the growth medium, with activity being highest in a medium containing sugars. Tricarboxylic acid cycle intermediates, such as malate, significantly reduced H2 utilisation. No reduction in the hydrogenase activity is observed when the enzyme is assayed directly by the tritium exchange method, indicating that the decrease in hydrogen uptake activity is not due to repression of hydrogenase biosynthesis. Cyclic AMP was found to alleviate the inhibition of H2 uptake by malate, and this requires new protein synthesis. Addition of chloramphenicol or rifampicin simultaneously with cyclic AMP eliminated the stimulation of H2 uptake in the malate medium. These results show that in R. japonicum cyclic AMP plays a major role in the regulation of H2 metabolism.


Contrast-enhanced ultrasonography revealed active thoracic bleeding.
A 61-year-old woman with a hepatocellular carcinoma located in the subphrenic region was treated by radiofrequency ablation (RFA) under artificial pleural effusion. During RFA, B-mode ultrasonography showed a swirling high echoic lesion in the artificial pleural effusion. A real-time scan performed using contrast-enhanced ultrasonography (CEUS) revealed a jet-like extravasation of contrast medium and pooling of microbubbles in the pleural cavity, which were confirmed by angiography. CEUS successfully identified the site of bleeding and can be regarded an effective tool for detecting active bleeding in an emergency.


[Interferon-alpha].
Among interferon (IFN)-alpha, beta, gamma, there are no differences in its clinical effects and toxicities. As to IFN-alpha, there are leukocyte IFN, lymphoblastoid IFN, recombinant IFN-alpha 2a, 2b, and 2c. Now we have largely completed the process of surveying for anticancer effects over the broad range of malignancies. However, the adequate method of administration, route, dose, and interval are not yet fully established. Dose response remains unanswered question with some contradictory results in in vitro and clinical reports. The actual mechanism responsible for its anticancer activity is still not known. The question of what variables to monitor in assessing adequate dosages of IFN remains unsolved. Several trials have examined the possibility of combining IFN with other treatment modalities including anticancer agents, BRMs, radiation, etc. It should be acknowledged that we remain at a very early stage in our understanding of IFN. In future, IFN may play an even larger role when used in an adjuvant setting or as part of multimodality cancer treatment.


The cot in cot deaths.
Little attention is paid to the cot in cot deaths. We report two cases of cot deaths which occurred in practically identical circumstances, with the infants lying face downwards in soft woven-type carrying baskets. The infants were probably unable to turn their heads to one side to maintain ventilation, due to the construction of these soft baskets with soft mattresses. This probably played an important role in the deaths.


A different pathway in the endoplasmic reticulum stress-induced expression of human HRD1 and SEL1 genes.
Human HRD1 and SEL1 are components of endoplasmic reticulum-associated degradation (ERAD), which is a retrograde transport mechanism from the ER to the cytosol for removing unfolded proteins. The expression of HRD1 and SEL1 was induced by ER stress-inducing agents and overexpression of both ER stress-responsive transcription factors, ATF6 and XBP1. Inhibition of IRE1 and ATF6 revealed that ER stress-induced HRD1 and SEL1 expressions are mediated by IRE1-XBP1- and ATF6-dependent pathways, respectively. These results suggest that the ER stress-induced ERAD gene expressions are mediated by different pathways, which are attributed to the differences in the promoter regions.


Promoting climate actions: A cognitive-constraints approach.
The present paper reports an experiment with a two-year-delayed (M = 695 days) follow-up that tests an approach to raising willingness to take political and personal climate actions. Many Americans still do not view climate change as a threat requiring urgent action. Moreover, among American conservatives, higher science literacy is paradoxically associated with higher anthropogenic climate-change skepticism. Our experimental materials were designed to harness the power of two central cognitive constraints - coherence and causal invariance, which map onto two narrative proclivities that anthropologists have identified as universal - to promote climate action across the political spectrum. Towards that goal, the essential role of these constraints in the causal-belief-formation process predicts that climate-change information would be more persuasive when it is embedded in a personal climate-action narrative, the evocation of which can benefit from exposure to parsimonious scientific explanations of indisputable everyday observations, juxtaposed with reasoners' own, typically less coherent explanations, occurring in a context that engages their moral stance. Our brief one-time intervention, conducted in ten U.S. states with the highest level of climate skepticism, showed that across the political spectrum, our materials raised appreciation of science, openness to alternative views, and willingness to take climate actions in the immediate assessment. It also raised how likely were reports two years later of having taken those actions or would have taken them had the opportunity existed, suggesting a long-lasting effect. Our approach adopts the framework that conceptions of reality are representations, and adaptive solutions in that infinite space of representations require cognitive constraints to narrow the search.


Crystal structure and functional characterization of SF216 from Shigella flexneri.
Shigella flexneri is a Gram-negative anaerobic bacterium that causes highly infectious bacterial dysentery in humans. Here, we solved the crystal structure of SF216, a hypothetical protein from the S. flexneri 5a strain M90T, at 1.7 Å resolution. The crystal structure of SF216 represents a homotrimer stabilized by intersubunit interactions and ion-mediated electrostatic interactions. Each subunit consists of three β-strands and five α-helices with the β-β-β-α-α-α-α-α topology. Based on the structural information, we also demonstrate that SF216 shows weak ribonuclease activity by a fluorescence quenching assay. Furthermore, we identify potential druggable pockets (putative hot spots) on the surface of the SF216 structure by computational mapping.


Latent space manipulation for high-resolution medical image synthesis via the StyleGAN.
This paper explores the potential of the StyleGAN model as an high-resolution image generator for synthetic medical images. The possibility to generate sample patient images of different modalities can be helpful for training deep learning algorithms as e.g. a data augmentation technique. The StyleGAN model was trained on Computed Tomography (CT) and T2- weighted Magnetic Resonance (MR) images from 100 patients with pelvic malignancies. The resulting model was investigated with regards to three features: Image Modality, Sex, and Longitudinal Slice Position. Further, the style transfer feature of the StyleGAN was used to move images between the modalities. The root-mean-squard error (RMSE) and the Mean Absolute Error (MAE) were used to quantify errors for MR and CT, respectively. We demonstrate how these features can be transformed by manipulating the latent style vectors, and attempt to quantify how the errors change as we move through the latent style space. The best results were achieved by using the style transfer feature of the StyleGAN (58.7 HU MAE for MR to CT and 0.339 RMSE for CT to MR). Slices below and above an initial central slice can be predicted with an error below 75 HU MAE and 0.3 RMSE within 4cm for CT and MR, respectively. The StyleGAN is a promising model to use for generating synthetic medical images for MR and CT modalities as well as for 3D volumes.


Salinity induced effects on the growth rates and mycelia composition of basidiomycete and zygomycete fungi.
Soil salinization, as the combination of primary and secondary events, can adversely affect organisms inhabiting this compartment. In the present study, the effects of increased salinity were assessed in four species of terrestrial fungi: Lentinus sajor caju, Phanerochaete chrysosporium, Rhizopus oryzae and Trametes versicolor. The mycelial growth and biochemical composition of the four fungi were determined under three exposure scenarios: 1) exposure to serial dilutions of natural seawater (SW), 2) exposure to serial concentrations of NaCl (potential surrogate of SW); and 3) exposure to serial concentrations of NaCl after a period of pre-exposure to low levels of NaCl. The toxicity of NaCl was slightly higher than that of SW, for all fungi species: the conductivities causing 50% of growth inhibition (EC50) were within 14.9 and 22.0 mScm-1 for NaCl and within 20.2 and 34.1 mScm-1 for SW. Phanerochaete chrysosporium showed to be the less sensitive species, both for NaCl and SW. Exposure to NaCl caused changes in the biochemical composition of fungi, mainly increasing the production of polysaccharides. When fungi were exposed to SW this pattern of biochemical response was not observed. Fungi pre-exposed to low levels of salinity presented higher EC50 than fungi non-pre-exposed, though 95% confidence limits overlapped, with the exception of P. chrysosporium. Pre-exposure to low levels of NaCl also induced changes in the biochemical composition of the mycelia of L. sajor caju and R. oryzae, relatively to the respective control. These results suggest that some terrestrial fungi may acquire an increased tolerance to NaCl after being pre-exposed to low levels of this salt, thus, suggesting their capacity to persist in environments that will undergo salinization. Furthermore, NaCl could be used as a protective surrogate of SW to derive safe salinity levels for soils, since it induced toxicity similar or higher than that of SW.


Influenza virus detection in the stool of children with acute gastroenteritis.
To determine if the clinical characteristics of children with gastroenteritis and influenza identified in their stool differ from those whose stool was influenza-negative. Children <18-years with gastroenteritis whose stool tested negative for enteropathogen were tested for influenza in stool. The clinical features between influenza-positive and influenza-negative gastroenteritis cases were compared. Stools from controls without infection were also tested for influenza. Among the 440 gastroenteritis cases, those who were influenza test-positive were older [median age 4.0 (IQR: 2.3, 5.5) vs. 1.5 (IQR: 0.5, 4.0) years; P = 0.008], more likely to present in fall or winter (92.3 % vs. 48.0 %; P = 0.001), be febrile (84.6 % vs. 30.6 %; P < 0.001), have respiratory symptoms (91.7 % vs. 44.8 %; P = 0.002), have dehydration [median Clinical Dehydration Scale score: 4 (IQR: 1.5, 4.5) vs. 2 (IQR: 0, 3); P = 0.034], and have higher Modified Vesikari Scale scores [median: 13 (IQR: 10.5, 14.0) vs. 10 (IQR: 9.0, 13.0); P = 0.044], than those who tested negative. Thirteen gastroenteritis cases (13/440; 3.0 %) including one child without respiratory symptoms vs. one control (1/250; 0.4 %) were influenza stool positive. Fever, respiratory symptoms, more severe illness, and older age were more common in children with gastroenteritis with influenza detected in stool, compared to those tested negative.


Data linkage in pharmacoepidemiology: A call for rigorous evaluation and reporting.
The purpose of this paper is to provide guidance on the evaluation of data linkage quality through the development of a checklist for reporting key elements of the linkage process. Responding to a call for manuscripts from the International Society for Pharmacoepidemiology (ISPE), a working group including international representation from the academic, industry, and contract research, and regulatory sectors was formed to develop a checklist for evaluation of data linkage performance and reporting data linkage specifically for pharmacoepidemiologic research. This checklist expands on the reporting of studies conducted using observational routinely collected health data specific to pharmacoepidemiology (RECORD-PE) guidelines. A key aspect of data linkage evaluation for pharmacoepidemiology is to articulate how a linkage process was performed and its accuracy in terms of validation and verification of the resulting linked data. This study generates a checklist, which covers domains including data sources, linkage variables, linkage methods, linkage results, and linkage evaluation. For each domain, specific recommendations provide a clear and transparent assessment of the linkage process. Linking data sources can help to enrich analytic databases to more accurately define study populations, enable adjustment for confounding, and improve the capture of health outcomes. Clear and transparent reporting of data linkage processes will help to increase confidence in the evidence generated from these data by allowing researchers and end users to critically assess the potential for bias owing to the data linkage process.


Evaluating the different laser fragmentation patterns used in laser cataract surgeries in terms of effective phacoemulsification time and power.
To evaluate the effects of the different fragmentation patterns for the lens nucleus in terms of the effective phacoemulsification time (EPT) and power. Shinagawa LASIK Center, Tokyo, Japan. Comparison study. Seventy-one eyes of 71 patients had preoperative lens opacity grading based on the Emery-Little Classification (Grade 1 and Grade 2). Eyes underwent femtosecond laser-assisted cataract surgery (Catalys™ Precision Laser System), for capsulotomy and lens fragmentation. For the lens fragmentation, either the quadrants softened (Quadrant) or the quadrants complete (Complete) pattern was used. The mean EPT and phacoemulsification (phaco) power for each cutting pattern of Grades 1 and 2 cataracts were evaluated. The mean EPT was 28.96 seconds in the Quadrant Group and 16.31 seconds in the Complete Group (P=0.006). The mean phaco power was 8.07% in the Quadrant Group and 4.77% in the Complete Group (P=0.0002). Comparing the Quadrant and Complete Groups of Grade 1 cataract showed no significant difference in EPT (P=0.16), but showed a significant difference in phaco power (P=0.033). Comparing the Quadrant and Complete patterns of Grade 2 cataract showed significant differences in both EPT (P=0.012) and phaco power (P=0.003). Using the Complete pattern showed a 44.7% reduction in EPT and a 40.9% reduction in phaco power when compared to the Quadrant Group. Using the smaller fragmentation pattern in femtosecond laser cataract surgery, the phaco time and power were reduced significantly when compared to the procedure with the larger fragmentation pattern.


A Systematic Review of the Factors that Patients Use to Choose their Surgeon.
Given surgery's inherent risks, a patient should be able to make the most informed decisions possible in selecting surgical treatment. However, there is little information on what factors patients deem important when choosing a surgeon. We performed a systematic review of the literature focused on how patients select surgical care, focusing on identification of factors that influence patient choice as well as important sources of information used by patients. A search of all available literature on factors associated with choice of surgeon/surgical care, as well as sources of information used by patients before undergoing surgery, was conducted using the MEDLINE/PubMed electronic database. Of the 2315 publications identified, 86 studies met inclusion criteria. Overall, patients draw upon a wide range of factors when choosing surgical care. Surgeon reputation and competency stood out as the most valued professional attributes. Patients also often selected surgeons based on their interpersonal skills. Many patients chose surgical care using hospital, rather than surgeon, characteristics. For these patients, hospital reputation and hospital distance were factors of primary importance. Importantly, most patients relied on word-of-mouth and physician referrals when choosing a surgeon. Patients also expressed interest in quality information on surgeons, indicating that these data would be useful in decision-making. Patients draw upon a myriad of factors when choosing a surgeon and the circumstances surrounding patients' decisions maybe differ based on sociodemographic, cultural, as well as other factors. Additional information on how patients choose surgeons or hospitals will help providers assist patients in finding their preferred caregivers.


[Study on the classification of gonococcal island of different genotypes and effects of sac-4 gene on serum resistance of Neisseria gonorrhoeae].
Using molecular methods to study the relationship between genotypes and serum resistance of Neisseria gonorrhoeae in Wuhan area. NG-mast and serum bactericidal assays at the molecular level were used to differentiate the 46 strains which were isolated from the outpatients of sexually transmitted disease clinics and the relationship between different genotypes while phenotypes was also studied. 80.43% of the 46 strains contained the island and we were able to define three different combinations of genes in the isolates. Results from serum bactericidal assays showed that all 9 sac-4+ strains did not provide any serum resistance. Different isolates carried different gonococcal genetic islands (pathogenicity island) and certain phenotypes. There were no sobious relationship between sac-4 gene and serum resistance of Neisseria gonorrhoeae.


Monoclonal antibodies in conditioning regimens for hematopoietic cell transplantation.
Monoclonal antibodies are increasingly being incorporated in conditioning regimens for autologous or allogeneic hematopoietic cell transplantation (HCT). The benefit of adding rituximab to autologous HCT regimens is purportedly related to in vivo purging of clonal B cells. Randomized trials comparing the addition (or not) of rituximab to high-dose therapy regimens are lacking. No benefit of standard-dose radioimmunotherapy-based regimens for autografting in aggressive lymphomas was seen in a randomized controlled study. The incorporation of rituximab into allogeneic HCT regimens aims to improve responses while reducing nonrelapse mortality resulting from acute graft-versus-host disease. The optimal dose and administration schedule of rituximab in this setting are unknown, and potentially serious complications from increased infections owing to prolonged (and profound) cytopenias or persistent hypogammaglobulinemia are of concern. Radioimmunotherapy-based conditioning for allografting holds promise as a modality to optimize tumor control and synergize adoptive immunotherapy effects, but it remains experimental at this time. The addition of alemtuzumab to allogeneic HCT regimens is associated with prolonged lymphopenia and impaired immune reconstitution, high relapse rates, and serious infections. The optimal dose and schedule of alemtuzumab to avoid prolonged immune paresis remain elusive. It is anticipated that additional monoclonal antibodies will soon become available that can be incorporated into HCT regimens after safety and clinical efficacy are demonstrated.


Caravan explosions: a case series of burns patients at the Royal Brisbane and Women's Hospital.
Caravan explosions due to gas cylinder explosions or gas leaks are responsible for a small but significantly injured group of burns patients. Those involved in explosions are sometimes assumed to be at risk of primary blast wave injury; however, the likelihood of such injuries is unclear. The aim of this research was to seek evidence of primary blast injury in groups defined by clinicians as having sustained burns in explosive and non-explosive events. This is a single-centre case series of patients with caravan-related burns from 2009 to 2019, identified using the burns data registry at the Royal Brisbane and Women's Hospital. Patients were divided into two groups based on the mechanism of injury, with injuries sustained from either a gas bottle explosion (group 1) or from gas ignition (group 2). Twenty-one patients were identified over the 10-year period. The explosion group suffered more extensive burns, with a median % total body surface area of 31% (23.5-43.5) and 9.5% (5-20) in group 1 and group 2, respectively (P = 0.01). There was a numerically longer median hospital and intensive care unit length of stay in group 1. In multivariable analysis, there were no statistically significant predictors of intensive care unit or hospital length of stay. None of the patients appeared to have suffered any of the expected effects of primary blast wave injury. Gas bottle explosions in caravans uncommonly, if ever, result in a blast wave of sufficient energy to cause primary blast injury.


The periplasmic binding protein NrtT affects xantham gum production and pathogenesis in Xanthomonas citri.
In Xanthomonas citri, the bacterium that causes citrus canker, three ATP-binding cassette (ABC) transporters are known to be dedicated to the uptake of sulfur compounds. In this work, using functional, biophysical and structural methods, we showed that NrtT, a periplasmic component of the ABC transporter NrtCB, is an alkanesulfonate-binding protein and that the deletion of the nrtT gene affected xantham gum synthesis, adhesion and biofilm production, similarly to the phenotype obtained in the X. citri ssuA-knockout strain, in which the alkanesulfonate-binding protein SsuA is absent. Although NrtA and SsuA share similar ligands, the function of these proteins is not complementary. These results emphasize that organic-sulfur sources are directly involved with bacterial infection in vivo and are needed for pathogenesis in X. citri.


Molecular recognition of carbohydrates: evaluation of the binding properties of pyrazole-based receptors and their comparison with imidazole- and indole-based systems.
The aim of the study was to evaluate the potential of pyrazole-based receptors in the complexation of carbohydrates. Representatives of a new series of acyclic pyrazole-based receptors were prepared and their binding properties toward selected mono- and disaccharides evaluated. The results of the binding studies were compared with those obtained for acyclic imidazole- and indole-based receptors. The first binding studies revealed di- vs monosaccharide binding preferences of the new receptors and showed that pyrazole units are useful building blocks for the construction of receptors with interesting binding preferences.


DNA polymorphisms of the KiSS1 3' untranslated region interfere with the folding of a G-rich sequence into G-quadruplex.
KISS1R and its ligand, the kisspeptins, are key hypothalamic factors that regulate GnRH hypothalamic secretion and therefore the pubertal timing. During studies analysing KiSS1 as a candidate gene in pubertal onset disorders, two SNP and one nucleotide insertion were observed in a 23 nucleotides G-rich sequence located 65 nucleotides downstream of the stop codon. The polymorphisms formed four haplotypes. Biophysical experiments revealed the ability of this G-rich sequence to fold into G-quadruplex structures and demonstrated that the three DNA polymorphisms did not perturb the folding into G-quadruplex but affected G-quadruplex conformation. A functional luciferase reporter-based assay revealed functional differences between 3'UTR haplotypes. These data show that polymorphisms in a G-rich sequence of the 3'UTR of KISS1, able to fold into G-quadruplex structures, can modulate gene expression. They highlight the potential role of this G-quadruplex in the regulation of KISS1 expression and in the timing of pubertal onset.


Total Synthesis of (+)-okaramine J featuring an exceptionally facile N-reverse-prenyl to C-prenyl aza-Claisen rearrangement.
[reaction: see text] The convergent total synthesis of (+)-okaramine J was achieved in a longest linear sequence of 12 steps from l-tryptophan tert-butyl ester. A key reaction was the acid-catalyzed room-temperature aza-Claisen rearrangement of a N-reverse-prenylated hexahydro[2,3-b]pyrroloindole to a C-prenylated derivative.


Altered Mitochondrial Dynamics Contributes to Propofol-induced Cell Death in Human Stem Cell-derived Neurons.
Studies in developing animals have shown that anesthetic agents can lead to neuronal cell death and learning disabilities when administered early in life. Development of human embryonic stem cell-derived neurons has provided a valuable tool for understanding the effects of anesthetics on developing human neurons. Unbalanced mitochondrial fusion and fission lead to various pathological conditions including neurodegeneration. The aim of this study was to dissect the role of mitochondrial dynamics in propofol-induced neurotoxicity. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick-end labeling staining was used to assess cell death in human embryonic stem cell-derived neurons. Mitochondrial fission was assessed using TOM20 staining and electron microscopy. Expression of mitochondrial fission-related proteins was assessed by Western blot, and confocal microscopy was used to assess opening time of the mitochondrial permeability transition pore (mPTP). Exposure to 6 h of 20 μg/ml propofol increased cell death from 3.18 ± 0.17% in the control-treated group to 9.6 ± 0.95% and led to detrimental increases in mitochondrial fission (n = 5 coverslips per group) accompanied by increased expression of activated dynamin-related protein 1 and cyclin-dependent kinase 1, key proteins responsible for mitochondrial fission. Propofol exposure also induced earlier opening of the mPTP from 118.9 ± 3.1 s in the control-treated group to 73.3 ± 1.6 s. Pretreatment of the cells with mdivi-1, a mitochondrial fission blocker rescued the propofol-induced toxicity, mitochondrial fission, and mPTP opening time (n = 75 cells per group). Inhibiting cyclin-dependent kinase 1 attenuated the increase in cell death and fission and the increase in expression of activated dynamin-related protein 1. These data demonstrate for the first time that propofol-induced neurotoxicity occurs through a mitochondrial fission/mPTP-mediated pathway.


How are you sleeping? Starting the conversation with fathers about their mental health in the early parenting years.
Approximately 1 in 10 fathers of infants experience symptoms of common mental health disorders, prompting calls for paternal postpartum screening. However, numerous obstacles exist to screening implementation. The aim of this study was to provide preliminary evidence for an alternative approach that starts with asking fathers about their sleep. Using self-reported father data at 0 to 36 months postpartum (N=1204) from four Australian cohort studies, we assessed associations between responses to various single-item questions about sleep (good to poor), and scores on validated measures of mental health (depression, anxiety and stress). We conducted regressions, unadjusted and adjusted for father age, child age, household income, education, first or later child, and marital status, to test associations between sleep and each indicator of mental health. We then meta-analyzed effects and assessed interactions between sleep and each of the covariates. Consistent associations between fathers' subjective poor sleep and depression, anxiety and stress were replicated across the four cohorts despite heterogeneity in the sleep questions. At the meta-analytic level, effects ranged from weak to moderate (0.25 to 0.37) and were robust to all adjustments. Interactions were only detected between family income and poor sleep, such that the association was stronger for high income fathers. This study does not address the sensitivity or specificity of single-item sleep questions for assessing paternal mental health risk. A low-cost, non-stigmatizing single question to postpartum fathers about their sleep may present a gateway opportunity to enquiring about mental health.


Safety of multiple stereotactic radiosurgery treatments for multiple brain lesions.
Stereotactic radiosurgery (SRS) is a widely used therapy for multiple brain lesions, and studies have clearly established the safety and efficacy of single-dose SRS. However, as patient survival has increased, the recurrence of tumors and the development of metastases to new sites within the brain have made it desirable to repeat treatments over time. The cumulative toxicity of multi-isocenter, multiple treatments has not been well defined. We have retrospectively studied 10 patients who received multiple SRS treatments for multiple brain lesions to assess the cumulative toxicity of these treatments. In a retrospective review of all patients treated with SRS using the X-knife (Radionics, Burlington, MA) at Westchester Medical Center/New York Medical College between December 1995 and December 2000, 10 patients were identified who received at least two treatments to at least 3 isocenters and had a minimum follow-up period of 6 months. Image fusion technique was used to determine cumulative doses to targeted lesions, whole brain and critical brain structures. Toxicities and complications were identified by chart and radiological review. The average of the maximum doses (cGy) to a point within the whole brain was 2402 (range 1617-3953); to the brainstem, 1059 (range 48-4126); to the right optic nerve, 223 (range 14-1012); to the left optic nerve, 159 (range 17-475); and to the optic chiasm, 219 (range 15-909). There were no focal neurological toxicities, including visual disturbances, cranial nerve palsies, or ataxia in any of the 10 patients. There were also no global toxicities, including cognitive decline or secondary tumors. Only one patient developed seizures that were difficult to control in association with radiation necrosis. Multiple SRS treatments at the cumulative doses used in our study are a safe therapy for patients with multiple brain lesions.


The possible inhibitory role of the leucine-zipper DNA binding protein c-fos in the regulation of hepatic gene expression after sepsis.
The leucine-zipper c-fos has been implicated in the regulation of gene expression. We investigated the possible role of c-fos in the regulation of hepatic gene expression after sepsis. Based on previous data demonstrating that sepsis inhibits hepatic gene expression of carnitine palmitoyltransferase (CPT), we hypothesized that c-fos may play a role in the inhibition of CPT gene expression after sepsis. We studied c-fos gene expression after peritoneal sepsis induced by cecal ligation and puncture (CLP) or sham-CLP. To investigate the possible inhibitory role of c-fos on CPT gene transcription, we investigated the effect of c-fos on c-jun-driven CPT promoter-chloramphenicol acyltransferase reporter gene expression in a HepG2 hepatoma cell cotransfection model. To investigate the possible role of cyclic adenosine monophosphate (cAMP) in the regulation of c-fos in vivo, we treated either the sham-CLP group or the CLP group with either vehicle or cAMP. Peritoneal sepsis in the rat model resulted in a four-fold increase in hepatic c-fos mRNA and c-fos protein. In the cotransfection model, c-fos significantly inhibited c-jun-induced chloramphenicol acyltransferase activity. Treatment with cAMP resulted in a 50% decrease in c-fos protein in either the sham-CLP or CLP group. We conclude that (1) sepsis increases hepatic c-fos transcription and translation, (2) c-fos inhibits c-jun-induced CPT gene expression, and (3) cAMP probably does not directly mediate the increase in c-fos after sepsis.


Imidazole-buffered osmium tetroxide: an excellent stain for visualization of lipids in transmission electron microscopy.
The usefulness of imidazole-buffered osmium tetroxide as a stain for lipids in transmission electron microscopy has been investigated. Rat liver and other tissues were fixed by perfusion with glutaraldehyde and post-fixed with osmium-imidazole and the appearance of lipid droplets was compared with that after post-fixation in unbuffered aqueous osmium tetroxide or an osmium solution buffered otherwise. Prominent electron-opaque staining of lipid droplets and of lipoprotein particles was noted after post-fixation with 2% osmium-imidazole, pH 7.5, for 30 min. The lipid droplets appeared well circumscribed with no evidence of diffusion. In contrast, the intensity of staining was much less and there was some diffusion around lipid droplets in material post-fixed in aqueous or cacodylate-buffered osmium tetroxide. Spot tests on filter paper revealed that unsaturated fatty acids, especially linolenic and linoleic acids reacted more intensely with osmium-imidazole than with aqueous osmium tetroxide. These findings demonstrate that osmium-imidazole provides an excellent stain for lipids in transmission electron microscopy and that most probably it stains lipids with unsaturated fatty acids.


Plasma serotonin monitoring by blood microdialysis coupled to high-performance liquid chromatography with electrochemical detection in humans.
Plasma serotonin (5-HT) active pool was monitored in male volunteers by intravenous microdialysis coupled to HPLC-EC with 98.6% efficient probes. 5-HT was monitored from 60 min before to 360 min after an oral dose of fluoxetine, a 5-HT uptake inhibitor, or vehicle. The basal values were within nanomolar range (0.55 to 4.6 ng/ml). After administration of fluoxetine, there was a significant increment of 5-HT with respect to controls. These results showed that intravenous microdialysis is an alternative efficient technique to monitor endogenous unbound 5-HT changes in plasma without extracting blood or sample pretreatment procedures before the chemical analysis.


Identification, evolution, and association study of a novel promoter and first exon of the human NOD2 (CARD15) gene.
Mutations in the NOD2 (CARD15) gene predispose to Crohn's disease (CD), a human chronic inflammatory bowel disorder, and can cause Blau syndrome. During an investigation of an apparent correlation between a frameshifting mutation in the canonical first exon of NOD2 of marmoset and tamarin species and their susceptibility to chronic colitis, we found that, contrary to previous reports, the basal levels of NOD2 transcripts in tissues relevant to CD arise from a distinct novel promoter and first exon. The canonical first exon, by contrast, seems to be of negligible transcriptional importance under physiological conditions, and its reading frame has been disrupted twice during primate evolution. Thus the main NOD2/CARD15 protein isoform produced in humans and other primates is 27 amino acids shorter than previously reported, starting at a conserved methionine in exon 2. We show that there is no significant association between variants in the novel NOD2 promoter region and CD.


Assessment of moyamoya disease using multidetector row computed tomography.
The recent introduction of multidetector row computed tomography (MDCT) scanners has enabled high-resolution 3-dimensional reconstruction. The purpose of this study was to establish a method to evaluate moyamoya disease using computed tomography angiography (CTA), specifically MDCT. Twenty-four patients (48 sides total) with moyamoya disease diagnosed by magnetic resonance angiography (MRA) were evaluated by means of CTA using MDCT by 3 independent observers, and the resulting 144 sides were analyzed. CTA and MRA were compared in terms of the steno-occlusive changes exhibited in each vessel. CTA and MRA scores were assigned on the basis of the severity of occlusive changes in the internal carotid artery, middle cerebral artery, anterior cerebral artery, and posterior cerebral artery. CTA scores were significantly correlated with MRA scores (P < .0001), and the 2 scores were in complete agreement in 57 sides (39.6%). The mean CTA score was significantly lower than the mean MRA score (P < .0001). Compared with CTA, MRA overestimated occlusion in 115 of the 576 vessels assessed. The mean MRA score was significantly higher in the overestimation group than in the good correlation group (P < .0001). CTA had a significantly higher rate of detection of moyamoya-affected vessels (P = .0001). Our data indicate that CTA using MDCT is a more reliable technique than MRA for diagnosing moyamoya disease. The ability to perform CTA quickly is a significant benefit for patients with moyamoya disease, particularly in pediatric and emergency cases.


A Preliminary Evaluation of Energy Efficiency for Children with Cerebral Palsy for Driving A Manual Wheelchair and Walking: Use of the Total Heart Beat Index.
Aims: This study aims to compare the total heart beat index (THBI) in evaluating energy efficiency between using a manual wheelchair and walking for children with cerebral palsy (CP). Methods: The energy efficiency was measured in 21 participants with CP (mean age, 13.6 ± 3.4 years) who walk or drive a manual wheelchair using a square course. THBI was calculated as total number of heart beats during the exercise period/total distance traveled. Results: Significant differences in the THBI were observed between Gross Motor Function Classification System (GMFCS) levels III and IV (p = .049, effect size = 1.60). No significant differences in THBI were observed between GMFCS levels II and III or between GMFCS levels II and IV (p > .05). Conclusions: The energy efficiency of children with CP who use a manual wheelchair in this study was equal to or better than that for walking.


Maximum-likelihood estimation of sensitivity and specificity of ELISAs and faecal culture for diagnosis of paratuberculosis.
The accuracy of three diagnostic tests for paratuberculosis was evaluated using maximum-likelihood estimation of sensitivity and specificity. We also explored the variety of estimates that can be obtained if the tests are to be used in populations of different composition with regard to infection and disease states. Two enzyme-linked immunosorbent assays (ELISAs) were evaluated separately with the faecal culture (FC). The study was carried out as a cross-sectional field study to cover all likely states of infection with Mycobacterium avium subsp. paratuberculosis.The three basic assumptions for the maximum-likelihood technique were evaluated to validate the results. Our accuracy estimates for the ELISAs were not very different from those previously published, but those for faecal culture differed if a different cut-off value was chosen for the ELISA. If faecal culture was used for screening in a Danish dairy region where the median ELISA reading was a measure of the general disease situation, the sensitivity of the faecal culture was 20-25%. If faecal culture was used as a confirmatory test on cows with a high ELISA reading (and thus high level of antibodies), the sensitivity of the faecal culture would be in the range 60-70%. These results emphasise the importance of the composition of a target population before selecting a specific diagnostic test for a given purpose. We concluded that faecal culture is useful for confirmation but not for screening purposes.


Vertical imbalance induced by prism-ballasted soft toric contact lenses fitted unilaterally.
Fitting a prism-ballasted soft toric contact lens unilaterally may potentially induce a vergence error that the subject cannot compensate. In the present study, a prism-ballasted (1.5Delta base down) soft toric contact lens was fitted in the right eye only of 10 subjects with normal binocular vision. The effect on binocular vision was evaluated by measuring vertical phoria adaptation and vertical fixation disparity adaptation. The results show that the vertical vergence error induced was well compensated and fully adapted to. However, care might be needed when fitting these lenses unilaterally in subjects with vertical phoria-related problems.


At last, a national health measurement survey program for Australia!
Objective assessment of the health of the population is the key to policy and planning.


Facial nerve dysfunction following parotidectomy: role of intraoperative facial nerve monitoring.
Facial nerve dysfunction (FND) is a frequent and serious parotidectomy outcome. Intraoperative facial nerve monitoring (IFNM) is an increasingly used technique to identify the facial nerve (FN) and minimize its injury. This study aimed to evaluate the determinant factors in the presence and severity of FND after parotidectomy, including IFNM. A total of 48 patients consecutively submitted to parotidectomy between 2005 and 2020 in a tertiary hospital were retrospectively analyzed. The House-Brackmann Scale (HBS) was used to assess the severity of FND. There was a mean age of 54.2 ± 17.8 years, 50% were male. Pleomorphic adenoma (41.7%) and Warthin's tumor (25.0%) were most common. From the 23 patients (47.9%) who developed some degree of FND (HBS score of 3.41 ± 1.53), 19 (82.6%) showed facial movement recovery, with a mean recovery time of 4.78 ± 2.53 months. IFNM was performed in 39.6% of the surgeries. The use of IFNM (p = 0.514), the type of surgery-partial or total parotidectomy-(p = 0.853) and the type of histology-benign or malignant lesion-(p = 0.852) did not significantly influence the presence of FND in the postoperative period. However, in the subgroup of patients who developed FND, the HBS value was significantly lower in cases of benign pathology (p = 0.002) and in patients who underwent IFNM (p = 0.017), denoting a significantly lower severity. In the present study, IFNM and the existence of a benign lesion have been shown to be associated with lower severity of FND.


Asymmetric implants for breast asymmetry.
The indications, advantages, and disadvantages of round and anatomical implants have previously been described. The principles of biodimensional implant selection have been developed by several authors, where the objective choice of breast prosthesis for augmentation is based on the patient's breast tissues. This process has largely been applied to anatomical implant selection. We report a case of breast asymmetry, where we have applied the same concepts in the selection of implants based on tissue dimension. This resulted in an anatomical implant being used to augment the left breast, and a round implant on the right. To our knowledge a round implant and an anatomical implant have not previously been employed in the same patient to correct breast asymmetry. This resulted in excellent postoperative symmetry.


Stoichiometric translocation of adipocyte insulin receptors from the cell-surface to the cell-interior. Studies using a novel method to rapidly remove detergent and concentrate soluble receptors.
A rapid one-step method was developed for harvesting and concentrating insulin receptors from solubilized adipocytes, which entails precipitating soluble receptors with polyethylene glycol and resuspending the receptor-containing pellet in a reduced volume of binding buffer. With this procedure 90-100% of receptors were recovered, while 80% of cellular protein was removed, thus resulting in a marked reduction of both ligand and receptor proteases and about a 5-fold purification of the receptor. More importantly, greater than 98% of the Triton X-100 detergent was removed during this procedure so that the reduced receptor affinity observed in solubilized extracts (due to detergent) was restored to normal. Reconstituted receptors exhibited normal binding characteristics similar to those observed for plasma membrane receptors. The general utility of our receptor precipitation-reconstitution method is highlighted by studies on insulin-induced translocation of receptors from the cell-surface to the cell-interior of adipocytes and studies on the assessment of the binding affinity of nascent intracellular receptors. The results of these studies are consistent with the following. 1) Insulin initiates endocytotic uptake of insulin receptors, which then recycle back to the cell-surface. 2) Chloroquine impairs the recycling of internalized receptors while preventing receptor degradation, resulting in the progressive trapping and accumulation of receptors within cells during insulin treatment. 3) Receptor translocation during acute insulin-induced down-regulation is stoichiometric in that receptors lost from the cell-surface can be quantitatively recovered within the cell-interior. 4) In the absence of ligand, these receptors within adipocytes are mainly newly synthesized receptors enroute to the cell-surface, and they possess an affinity similar, if not identical, to mature receptors on the plasma membrane.


Comparison of Transthoracic Contrast Echocardiography with High-Resolution Chest CT after Embolization of Pulmonary Arteriovenous Malformation.
To compare postembolotherapy follow-up graded transthoracic contrast echocardiography (TTCE) and high-resolution computed tomography (CT) of the chest and to evaluate the use of graded TTCE in the early postembolic period. Thirty-five patients (6 men and 29 women; mean age, 56 years; range, 27-78 years) presenting for postembolotherapy follow-up between 2017 and 2021 with concurrent high-resolution CT and graded TTCE were analyzed retrospectively. Untreated pulmonary arteriovenous malformations (PAVMs) with a feeding artery of ≥2 mm were considered treatable. Ninety-four percent of patients (33 of 35) did not have treatable PAVMs on high-resolution CT. TTCE was negative for shunts (Grade 0) in 34% of patients (n = 12). Of patients with a TTCE positive for shunts (23 of 35, 66%), 83% had a Grade 1 shunt, 13% had a Grade 2 shunt, and 4% had a Grade 3 shunt. No patient with a Grade 0 or 1 shunt had a treatable PAVM on high-resolution CT. Of the 2 patients with PAVMs requiring treatment, one had a Grade 2 shunt and one had a Grade 3 shunt. TTCE grade was significantly associated with the presence of a treatable PAVM on high-resolution CT (P < .01). Graded TTCE predicts the need for repeat embolotherapy and does so reliably in the early postembolotherapy period. This suggests that graded TTCE can be utilized in the postembolotherapy period for surveillance, which has the potential to lead to a decrease in cumulative radiation in this patient population.


[Diagnosis and treatment of malignant polyps of the rectum and sigmoid].
By means of cytological and histological methods of investigation malignant transformation of rectal and sigmoid polyps was revealed in 6.3% among 127 patients suffering polyps. Electroexcision of tumors resulting in persistent cure is felt to be the method of choice in treatment of such patients.