CT artifacts from port systems: Virtual monoenergetic reconstructions from spectral-detector CT reduce artifacts and improve depiction of surrounding tissue.
CT artifacts from port-systems are a common problem in staging- and restaging-examinations and reduce image quality and diagnostic assessment. The purpose of this study was to investigate the reduction of these artifacts using virtual monoenergetic images (VMI) from dual-energy spectral-detector CT (SDCT) in comparison to conventional CT-images (CI). 50 SDCT-datasets of patients with artifacts from port-chamber and port-catheters were included in this IRB-approved, retrospective study. CI and VMI (range, 40-200 keV, 10 keV increment) were reconstructed from the same acquisition. The quantitative image analysis was performed ROI-based assessing mean and standard deviation of attenuation (HU) in most pronounced hypo- and hyperdense artifacts surrounding to the port-chamber and the distal end of the port-catheter in the superior vena cava. Subjectively, artifact reduction and diagnostic assessment of surrounding soft tissue were rated on 5-point Likert-scales. In comparison to CI, VMI of higher keV-values showed strong reduction of hypo- and hyperattenuating artifacts around the port-chamber and port-catheter (CI/VMI200keV: hypodense -104.7 ± 124.7HU/10.8 ± 58.1HU and -101.6 ± 101.5HU/-36.7 ± 32.9HU; hyperdense 240.8 ± 151.6HU/79.6 ± 81.3HU and 108.6 ± 129.3HU/25.9 ± 31.9HU; all p < 0.001). Image noise could also be reduced significantly. The subjective analysis showed significantly reduced artifacts around the port-chamber and port-catheter (CI/VMI200keV: hypodense 3(1-4)/5(4-5) and 3(2-4)/5(4-5); hyperdense 3(1-4)/5(4-5) and 3(2-3)/5(3-5); all p < 0.001) and improved diagnostic assessment of pectoral/subclavian soft tissue for VMI of ≥100keV. Ratings for diagnostic assessment were best between 140-200 keV. Overall interrater agreement was high (ICC = 0.79). Higher keV VMI enabled a significant reduction of artifacts from port-systems around the chamber and the catheter leading to improved assessment of surrounding soft tissue.


Targeting acid sphingomyelinase reduces cardiac ceramide accumulation in the post-ischemic heart.
Ceramide accumulation is known to accompany acute myocardial ischemia, but its role in the pathogenesis of ischemic heart disease is unclear. In this study, we aimed to determine how ceramides accumulate in the ischemic heart and to determine if cardiac function following ischemia can be improved by reducing ceramide accumulation. To investigate the association between ceramide accumulation and heart function, we analyzed myocardial left ventricle biopsies from subjects with chronic ischemia and found that ceramide levels were higher in biopsies from subjects with reduced heart function. Ceramides are produced by either de novo synthesis or hydrolysis of sphingomyelin catalyzed by acid and/or neutral sphingomyelinase. We used cultured HL-1 cardiomyocytes to investigate these pathways and showed that acid sphingomyelinase activity rather than neutral sphingomyelinase activity or de novo sphingolipid synthesis was important for hypoxia-induced ceramide accumulation. We also used mice with a partial deficiency in acid sphingomyelinase (Smpd1(+/-) mice) to investigate if limiting ceramide accumulation under ischemic conditions would have a beneficial effect on heart function and survival. Although we showed that cardiac ceramide accumulation was reduced in Smpd1(+/-) mice 24h after an induced myocardial infarction, this reduction was not accompanied by an improvement in heart function or survival. Our findings show that accumulation of cardiac ceramides in the post-ischemic heart is mediated by acid sphingomyelinase. However, targeting ceramide accumulation in the ischemic heart may not be a beneficial treatment strategy.


Promoting biological phosphorus removal in a full scale pre-denitrification wastewater treatment plant.
A survey conducted in Italy revealed that less than 0.5% out of a sample of over 2,000 municipal wastewater treatment plants is equipped with an enhanced biological phosphorus removal process. Conditions promoting biological phosphorus removal have been investigated by monitoring three real plants equipped with, respectively: (A) simultaneous chemical precipitation; (B) enhanced biological removal powered by chemical precipitation; (C) tertiary chemical precipitation with evidence of phosphate accumulating bacteria. An anaerobic compartment revealed essential for the growth of these microorganisms, the readily degradable organic concentration in the influent playing a minor role. Mapping dissolved oxygen and oxidation-reduction potential in different compartments of plant (C) was carried out to understand the reasons why phosphate accumulating bacteria were found even in the absence of anaerobic reactor. Finally, the possibility to exploit the biological phosphorus removal in plant (C), by adjusting the aeration conditions, was explored and an economic analysis showed this to be a preferable approach with respect to the chemical removal of phosphorus.


Zinc Supplementation in Preterm Neonates with Jaundice: Is it Beneficial?
Neonatal jaundice is a common neonatal disease that has adverse effects on neonates, especially preterm neonates, when indirect bilirubin level is adequately high to pass the blood-brain barrier, causing bilirubin encephalopathy or kernicterus. This study aimed to investigate the value of zinc (Zn) supplementation in preterm neonates with jaundice and whether it will be beneficial. A prospective randomized clinical trial, with the identification number TCTR20200504007, was conducted at Tanta University Hospital from July 2016 to March 2018 on 200 preterm neonates with jaundice. The studied neonates were divided into two groups: group 1, which received Zn and phototherapy, and group 2, which received phototherapy only and did not receive Zn. In group 1, 100 preterm neonates with jaundice received Zn as 0.6 mL (cm3) of zinc origin/kg/day orally through the oro-nasogastric tube divided into two doses (every 12 h), which was equal to 1.2 mg elemental zinc/kg/day orally for 10 days. There was no significant difference in serum bilirubin level between the two groups on the 2nd, 4th, and 6th days of admission, while the serum bilirubin level was significantly decreased in group 1 compared with that in group 2 only on the 8th, 9th, and 10th days of admission. The p-- values were 0.045*, 0.027*, and 0.004*, respectively. Zn administration to preterm neonates with jaundice was found to be beneficial in decreasing serum bilirubin level. Zn supplementation should be provided to preterm neonates with jaundice.


Hand-grip dynamometry provides a valid indication of upper extremity strength impairment in home care patients.
This retrospective study investigated the validity of hand-grip dynamometry with respect to its use in predicting generalized upper extremity strength. The records of 37 patients (mean average age, 77.7 years) receiving home care were used. Discriminant construct validity was examined by comparing their dynamometry measurements with measurements of age- and gender-matched healthy individuals reported in the literature. Convergent construct validity was described by the correlations of their dynamometry measurements and manual muscle test scores of the upper extremities. The patients' dynamometer-measured grip forces were significantly less than reported normative values. The patients' dynamometer measured grip forces were correlated significantly with their manual muscle test scores. These findings support the construct validity of hand-grip dynamometry for characterizing upper extremity strength impairment among adults treated in a home care setting.


Contextual signaling in cancer.
The formation and maintenance of an organism are highly dependent on the orderly control of cell growth, differentiation, death, and migration. These processes are tightly regulated by signaling cascades in which a limited number of molecules dictate these cellular events. While these signaling pathways are highly conserved across species and cell types, the functional outcomes that result from their engagement are specified by the context in which they are activated. Using the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome as an illustrative platform, we discuss how NF1/RAS signaling can create functional diversity at multiple levels (molecular, cellular, tissue, and genetic/genomic). As such, the ability of related molecules (e.g., K-RAS, H-RAS) to activate distinct effectors, as well as cell type- and tissue-specific differences in molecular composition and effector engagement, generate numerous unique functional effects. These variations, coupled with a multitude of extracellular cues and genomic/genetic changes that each modify the innate signaling properties of the cell, enable precise control of cellular physiology in both health and disease. Understanding these contextual influences is important when trying to dissect the underlying pathogenic mechanisms of cancer relevant to molecularly-targeted therapeutics.


Positive experiences and the relationship between stress and asthma in children.
Ninety children aged 6 to 13 y and suffering from chronic asthma were included in a prospective follow-up study lasting 18 mo in order to assess whether life events involving substantial positive effects on the child can protect against the increased risk associated with stressful life events. The main outcome measures included positive life events, positive long-term experiences, severely negative life events, chronic psychosocial stress and new asthma exacerbation. The results showed that, provided they occurred in close proximity to severely negative life events, positive life events, generally related to the child's own achievements, afforded protection against the increased risk of a new asthma exacerbation precipitated by severe events in children whose lives were marked by low to medium levels of chronic stress. No such effect was found in children exposed to high chronic stress nor did long-term positive experiences, such as when the child has a rewarding hobby, affect the asthma risk. Life events with a definite positive effect can counteract the increased risk of an asthma exacerbation precipitated by a severely negative life event, provided the chronic stress is only of low to medium level. Because this protective influence does not apply where there is high chronic stress, reducing this condition must be seen as a priority in children suffering from asthma, as these children are also more vulnerable to negative life events precipitating asthma exacerbation.


The cellular biology of angiotensin: paracrine, autocrine and intracrine actions in cardiovascular tissues.
A growing body of evidence suggests that angiotensin II, the effector protein of the renin-angiotensin system, is intimately involved with cell growth in target tissues. Most recently, evidence has been provided to indicate that angiotensin II is capable of inducing a hypertrophic response in cultured arterial smooth muscle cells. At the same time, considerable evidence has been developed to indicate that local analogs of the systemic renin-angiotensin system exist in multiple tissues and, in particular, in the vascular wall and the heart. Finally, data have accumulated to indicate that local growth regulatory factors, in many instances operating through regulation of proto-oncogene transcription, are involved in the hypertrophic and hyperplastic sequelae of hypertension. Included amongst these growth factors is angiotensin II. Thus, accumulating data indicate that angiotensin II is a growth factor with potential implications for the development of the sequelae of hypertension. In addition, studies from this laboratory and others suggest that angiotensin acts at least partially through what we have called an "intracrine" mechanism to produce its effects. In these multiple actions, angiotensin may provide a paradigm for other peptide growth factors and hormones.


[Use of anodization for the protective and surface finishing of dental instruments made of aluminum alloys].
Based on a study of thickness, quality and corrosion resistance of anodized films deposited on aluminium alloys D16T and B95 depending on electrolyte composition and oxidation parameters the optimum composition and operating process for the above alloys are established. The oxidation parameters affect in a much less degree the quality of films deposited on the alloy B95 thus permit recommending it for production of medical instruments.


A decade of research on Incontinence-Associated Dermatitis (IAD): Evidence, knowledge gaps and next steps.
Incontinence-Associated Dermatitis (IAD) is one of the clinical manifestations of Moisture- Associated Skin Damage (MASD). IAD is a common problem in aged patients with fecal and/or urinary incontinence. Update about IAD terminology, etiology, epidemiology, observation, prevention, and treatment. Integrative review. The lack of an ICD-10 code and an internationally validated and standardized method for IAD data collection contribute to a variation in epidemiological data. Frequent episodes of incontinence (especially fecal), occlusive containment products, poor skin condition, reduced mobility, diminished cognitive awareness, inability to perform personal hygiene, pain, pyrexia, certain medications (antibiotics, immunosuppressants), poor nutritional status, and critical illness are associated with IAD. Correctly diagnosing IAD and distinguish it from pressure ulcers is difficult. Even though the clinical presentation of partial thickness pressure ulcers and IAD is similar, the underlying etiologic factors differ. However, incontinence and IAD were found to be risk factors for pressure ulcer development. IAD management should essentially focus on skin cleansing to remove dirt, debris and microorganisms; skin moisturization to repair or augment the skin's barrier; and the application of a skin barrier product to prevent skin breakdown by providing an impermeable or semi-permeable barrier on the skin. The body of evidence is still limited, but growing since the last decade. Incontinence causes disruptions of the skin barrier function and leads to superficial skin damage. Macerated skin and superficial skin changes due to incontinence are associated with pressure ulcer development. Skin maceration, chemical irritation, and physical irritation should be targeted to effectively prevent and treat IAD.


Ultrastructural features of NPY-containing neurons in the rat striatum.
In the present study, we examined the ultrastructure of striatal neurons containing neuropeptide Y (NPY) which were labeled by an immunohistochemical method using peroxidase-conjugated F(ab) fragments in the rat. Each of the 26 neurons identified had a deeply indented oval nucleus. The cytoplasm, which was mainly concentrated at the emergence of the dendrites, contained an abundant Golgi apparatus and a well-developed granular endoplasmic reticulum. Dendrites were poorly branched and rarely exhibited varicosities or dendritic spines. NPY-immunoreactive (Ir) axons were small in diameter and unmyelinated. These features corresponded to a subpopulation of striatal neurons classified as aspiny type IV in previous Golgi studies. Axon terminals forming symmetrical synapses were numerous on the NPY-Ir perikarya and proximal dendrites. On distal NPY-Ir dendrites, synaptic contacts were mainly of the asymmetrical type, suggesting that NPY neurons are contacted by at least 2 categories of afferent fibers. Several NPY-Ir axonal processes and boutons were found to form symmetrical synapses with dendrites, dendritic spines and perikarya belonging to spiny type neurons. These data were consistent with the view that NPY may act as a neurotransmitter of striatal interneurons. Moreover, the frequent observation of NPY axonal processes in the close vicinity of striatal vessels suggested that NPY might also play a role in the control of cerebral vasomotricity. Thirty hours after intranigral injection of 6-hydroxydopamine to induce a degeneration of nigrostriatal dopamine terminals, some characteristic degenerative boutons were observed in close apposition to NPY-Ir cell bodies, suggesting that NPY neurons are under a direct nigrostriatal dopaminergic influence.


Role of calcium and cyclic adenosine 3':5' monophosphate in regulating smooth muscle contraction. Mechanisms of excitation-contraction coupling in smooth muscle.
Caclium initiates smooth muscle contraction by activating an enzyme, myosin light chain kinase. This enzyme catalyzes the transfer of phosphate from adenosine triphosphate to the 20,000 dalton light chain of myosin. In its phosphorylated form myosin interacts with actin to produce muscle contraction. The mechanism by which calcium activates myosin kinase requires (1) the binding of calcium to a 16,500 dalton calcium-binding protein (calmodulin), and (2) the binding of calmodulin-calcium to a 125,000 dalton catalytic subunit. This two protein complex is the active form of myosin light chain kinase. Smooth muscle relaxation is mediated by cyclic adenosine 3':5' monophosphate (cyclic AMP). One nechanism by which the latter may exert a direct effect on actin-myosin interaction is through the activation of a cyclic AMP-dependent protein kinase that can phosphorylate the 125,000 dalton component of myosin light chain kinase. Phosphorylation of myosin light chain kinase decreases the activity of the enzyme, thus favoring the unphosphorylated form of myosin, which cannot interact with actin to produce smooth muscle contraction.


Pharmacokinetics of flunitrazepam following single dose oral administration in liver disease patients compared with healthy volunteers.
The pharmacokinetic behaviour of flunitrazepam and its main active metabolite, N-desmethyl flunitrazepam, was investigated in 12 patients with liver disease (cirrhosis or hepatitis) compared to 6 healthy volunteers. A gas-liquid chromatographic method allowing for simultaneous determination of flunitrazepam and N-desmethyl flunitrazepam in plasma samples was developed. The accuracy and the precision near the quantification limit of ca. 1 ng/ml were better than 5%. Plasma levels of flunitrazepam were not significantly altered by hepatic failure, whereas plasma levels of N-desmethyl flunitrazepam were lower in patients than in healthy subjects. Pharmacokinetic parameters did not differ significantly between healthy subjects and liver disease patients: the oral clearance was 3.5 +/- 0.8, 3.5 +/- 1.9 and 4.0 +/- 1.2 ml/min/kg, respectively in healthy subjects, patients with hepatitis and patients with cirrhosis. The apparent elimination half-life was 22 +/- 5 h in healthy subjects, 25 +/- 10 h in patients with hepatitis and 20 +/- 6 h in patients with cirrhosis. However, the expected increase of the drug free fraction during liver disease could decrease the therapeutic and toxic ranges of flunitrazepam in these patients.


Correlation analysis between risk factors, BMD and serum osteocalcin, CatheK, PINP, β-crosslaps, TRAP, lipid metabolism and BMI in 128 patients with postmenopausal osteoporotic fractures.
Our aim is to investigate the correlation between risk factors of postmenopausal osteoporotic fracture, BMD and Bone turnover markers, lipid metabolism and BMI. The Cox proportional hazard model was used to conduct univariate and multivariate analysis to screen the risk factors related to postmenopausal osteoporotic fractures. Blood samples were collected to detect biochemical markers of bone turnover, blood lipids content, and then measure the BMI of the survey subjects. BMD was measured and its correlation with biochemical markers of bone turnover, lipid metabolism and BMI was analyzed. Cox univariate analysis indicated that average age, menopause, years since menopause, number of deliveries, and limb spasm are associated covariates of postmenopausal osteoporotic fractures. Where, BMD severity, history of hysterectomy or ovariectomy, and years since menopause are significant covariates for the incidence of postmenopausal osteoporotic fractures. The correlation study with lipid metabolism found that the smaller the BMI value, the greater the BMD loss; the smaller the TG value, the greater the BMD loss, exhibiting a downward trend. No difference was observed between HDL-C and LDL-C content, and the difference was not statistically significant (p>0.05). Femoral neck BMD was negatively correlated with CatheK, serum osteocalcin, PINP, β-crosslaps and TRAP, and lumbar spine BMD was also negatively correlated with CatheK, serum osteocalcin, PINP, β-crosslaps and TRAP. Biochemical markers of bone turnover are highly expressed in postmenopausal women and increase with the decrease of bone density, which can be used as markers for disease prediction. Combined with BMI, triglyceride and other related indicators, and closely related factors such as the patient's age, the number of deliveries, it is possible to predict the incidence of PMOP fractures early.


Tissue-integrated prostheses for edentulous patients with normal and abnormal jaw relationships.
Diagnosis and treatment planning are keys to successful prosthodontic rehabilitation. The increasing interest in the use of the tissue-integrated prosthesis to resolve the problems of edentulous patients indicates caution in the selection of patients for this procedure. Even if patients are identified who could potentially benefit, application of the concept must meet the needs of the patient. The treatment planning phase must include all professionals participating in patient management and must consider the best placement of fixtures to improve patient findings to an optimal degree. Although many patient factors must be considered in treatment planning, this article discussed application of the tissue-integrated prosthesis concept as it relates to jaw relationship. The tissue-integrated prosthesis must not compound or create retention and stability problems found with complete dentures. This article suggests treatment considerations in planning the tissue-integrated prosthesis for normal and abnormal jaw relationships.


Asymmetric synthesis of enantioenriched (+)-elaeokanine A.
The key transformation in the total synthesis of (+)-elaeokanine A was accomplished by asymmetric deprotonation of N-Boc pyrrolidine, followed by the reaction of the in situ generated enantioenriched stereogenic cuprate reagent with (E)-4-bromo-1-iodo-1-trimethylsilyl-1-butene with retention of configuration. N-Boc deprotection, followed by a one-pot olefin isomerization and intramolecular amine alkylation afforded a bicyclic vinyl bromide that was converted into (+)-elaeokanine A by sequential halogen metal exchange and reaction of the organolithium reagent with N-butanoylmorpholine.


Role of biliary phosphatidylcholine in the absorption and transport of dietary triolein in the rat.
This study was undertaken to determine the role of luminal phosphatidylcholine in the intestinal absorption and transport of glycerol trioleate in the rat. Rats with bile and thoracic duct lymph fistulas were infused with a bile salt-stabilized emulsion of glycerol trioleate only or with either dioleoyl or dipalmitoyl phosphatidylcholine added. Uptake of infused lipid was greater than 95% in all groups. The presence of supplemental phosphatidylcholine in the infusate greatly enhanced the lymphatic triglyceride and phosphatidylcholine outputs in the bile-diverted rats as compared with rats without phosphatidylcholine supplementation. There was no difference in lipid outputs between the dioleoyl or dipalmitoyl phosphatidylcholine-supplemented rats. The fatty acid pattern of the lymph phosphatidylcholine of the two groups of phosphatidylcholine-supplemented rats reflected that of the added phosphatidylcholine. In the absence of luminal phosphatidylcholine there was increased accumulation of mucosal triglyceride and evidence suggesting increased portal transport of absorbed fatty acid. Therefore, this study demonstrated that the presence of luminal phosphatidylcholine is important for the normal lymphatic transport of the absorbed digestion products of triglyceride, the major dietary fat.


Effect of major components of Tripterygium wilfordii Hook. f on the uptake function of organic anion transporting polypeptide 1B1.
Organic anion transporting polypeptide 1B1 (OATP1B1), which is specifically expressed at the basolateral membrane of human hepatocytes, is well recognized as the key determinant in the pharmacokinetics of a wide variety of drugs and considered as an important drug-drug interaction (DDI) site. Triptergium wilfordii Hook. f. (TWHF) is a traditional Chinese medicine that has a long history in treating diseases and more pharmacological effects were demonstrated recently. Components of TWHF mainly belong to the groups of alkaloids, diterpenoids, and triterpenoids. However, whether TWHF constituents are involved in herb-drug interaction (HDI) remains largely unknown. In the present study, we investigated the effect of four major components of TWHF, i.e. Triptolide (TPL), Celastrol (CL), and two alkaloids Wilforine (WFR) and Wilforgine (WFG) on the function of OATP1B1. It was found that co-incubation of these compounds greatly inhibited the uptake function of OATP1B1, with WFG (IC50 = 3.63 ± 0.61 μM) and WFR (IC50 = 3.91 ± 0.30 μM) showing higher inhibitory potency than TPL (IC50 = 184 ± 36 μM) and CL (IC50 = 448 ± 81 μM). Kinetic analysis revealed that co-incubation of WFG or WFR led to the reduction of both Km and Vmax of the DCF uptake. On the other hand, pre-incubation of WFG or WFR increased Km value of OATP1B1; while CL affected both Km and Vmax. In conclusion, co- and pre-incubation of the tested TWHF components inhibited OATP1B1 activity in different manners. Although co-incubation of WFG and WFR did not seem to directly compete with the substrates, pre-incubation of these alkaloids may alter the substrate-transporter interaction.


[Keratoderma palmoplantaris varians (striata et areata), a form of chronic idiopathic acrokeratosis described by Degos].
We report a case of a 15-year-old boy with hyperkeratotic lesions that were linear or striated on the palms and nummular on the soles. He was the only family member known to be affected, suggesting that the condition could be attributed to a de novo mutation or the recessive form of keratoderma palmoplantaris striata, described by Degos as chronic idiopathic acrokeratosis. The lesions did not improve with topical treatments (keratolytic agents, emollients, or corticosteroids) or oral retinoids. We observed that scratching of the affected areas was the main reason for deterioration of the lesions.


Impact and trade off analysis of land use change on spatial pattern of ecosystem services in Chishui River Basin.
The motivation of this fundamental research is to reveal the response of ecosystem services to land use change and to support the sustainable development of ecology, economy, and society. Considering the fragile eco-environment, intensive man-land relationship and the world-famous production base of Moutai liquor in China, we select Chishui River Basin (CRB) as the research region. In this study, the InVEST model is used to evaluate the impact of land use change on the spatial pattern of four ecosystem services including water yield, soil retention, carbon storage, and nitrogen export. Meanwhile, the spatial differentiation characteristics, service level, and trade-off using Pearson correlation analysis of each ecosystem service from 2000 to 2020 are explored. The results show the following: (1) The forest increased, while the grassland and cultivated decreased. Especially, the developed has increased greatly from [Formula: see text] to [Formula: see text]. (2) Each ecosystem service has spatio-temporal heterogeneity. The water yield and nitrogen export decreased, while soil retention and carbon storage showed an upward trend. (3) There are great differences in the level of ecosystem services among different land use types. The soil retention and carbon storage of forest are the highest, and the water yield of developed is the highest. (4) There are trade-offs and synergies among ecosystem services, such as the trade-off between water yield and soil retention is increasing, the synergetic relationship between water yield and nitrogen export is decreased. This is important evidence that the forest plays a major role in providing ecosystem services, and the improvement of watershed ecological services generally benefits from the implementation of ecological governance projects in recent years. However, it is worth noting that the frequent changes in land use and the intensification of urbanization have also brought potential risks to the local ecology. Therefore, all our preliminary results throw light on the nature of the impact of land use change on ecology and the trade-off relationship of ecosystem services, which is conducive to scientific protection of watershed ecological environment and the formulation of reasonable land use planning policies.


Quantifying the change in streamflow complexity in the Yangtze River.
Hydrological processes of the Yangtze River have changed over the past decades due to environmental change and human activity. This paper uses sample entropy to investigate the spatial distribution and dynamic change in streamflow series complexity in the Yangtze River, China. In this study, the complexity of the streamflow series is quantified by entropy analysis. Daily streamflow series for four stations located in the mainstem and two control stations of the two largest freshwater lakes were analysed for the past 60 years. The results showed that the complexity of the streamflow series showed an obvious spatial difference and an increasing trend from upstream to downstream in the Yangtze River. There was a negative relationship between the annual streamflow and the corresponding sample entropy, and their peak-to-valley values showed well-corresponding relationships. The complexity of the runoff series at the Cuntan, Yichang, and Datong stations showed a continuous increasing trend, while that of the Hankou station showed a decreasing trend. The Three Gorges Dam changed the streamflow series complexity in the middle reach of the Yangtze River during the initial impoundment stage, while it had only slight impacts during the fully operational stage. Compared to the mainstem reaches, the streamflow series complexity of the two lakes showed no obvious change. The complexity of the streamflow series in the mainstem of the Yangtze River has been influenced by dam construction. The study could provide a scientific reference for understanding the flow dynamic evolution in the Yangtze River.


A simple technique of laparoscopic port closure allowing wound extension.
Reliable and safe access to the abdominal cavity and efficient removal of the resected gallbladder are essential to laparoscopic cholecystectomy. The unpredictable size of the cholecystectomy specimen can sometimes lead to frustration at the time of removal. A simple technique has been developed that allows for tissue extraction and easy fascial closure regardless of the size of the specimen. This is achieved by using a four bite "U-shaped" purse string at the time of Hasson insertion, with cephalad advancement of the proximal two bites. This allows for variable wound extension and secure closure, without the need for additional sutures.


Involvement of anti-inflammatory heme oxygenase-1 in the inhibitory effect of curcumin on the expression of pro-inflammatory inducible nitric oxide synthase in RAW264.7 macrophages.
Curcumin, at high concentrations (>2 microM), inhibits the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS) through inactivation of nuclear factor (NF)-kappaB and, at low concentrations, induces the expression of heme oxygenase (HO)-1 in macrophages. Here, we demonstrated that curcumin at low concentrations (0.5-2 microM) can also inhibit NO production and iNOS expression in lipopolysaccharide (LPS)-activated RAW264.7 macrophages only when the cells were pretreated for at least 6h with curcumin. Curcumin induced dose- and time-dependent HO-1 expression, and this was coincident with the inhibitory effects of low concentrations of curcumin on NO production and iNOS expression. Blockage of HO-1 activity or knockdown of HO-1 expression abolished the inhibitory effects of curcumin. Over-expression of HO-1 or exogenous addition of carbon monoxide, a byproduct derived from heme degradation, mimicked the inhibitory action of low concentrations of curcumin. Moreover, LPS-induced NF-kappaB was diminished in macrophages subjected to prolonged treatment with low concentrations of curcumin. Treatment with HO inhibitor abolished the inhibitory effect of curcumin on LPS-induced NF-kappaB activation. Collectively, we provide evidence to support the important role of HO-1 in inhibition of NO production and iNOS expression by curcumin even at low concentrations.


The distribution of IL-13 receptor alpha1 expression on B cells, T cells and monocytes and its regulation by IL-13 and IL-4.
To study the expression of IL-13 receptor alpha1 (IL-13Ralpha1), specific monoclonal antibodies (mAb) were generated. Surface expression of the IL-13Ralpha1 on B cells, monocytes and T cells was assessed by flow cytometry using these specific mAb. Among tonsillar B cells, the expression was the highest on the IgD+ CD38- B cell subpopulation which is believed to represent naive B cells. Expression was also detectable on a large fraction of the IgD-CD38- B cells but not on CD38+ B cells. Activation under conditions which promote B cell Ig class switching up-regulated the expression of the receptor. However, the same stimuli had an opposite effect for IL-13Ralpha1 expression levels on monocytes. While IL-13Ralpha1 mRNA was clearly detectable in T cell preparations, no surface expression was detected. However, permeabilization of the T cells showed a clear intracellular expression of the receptor. A soluble form of the receptor was immunoprecipitated from the supernatant of activated peripheral T cells, suggesting that T cell IL-13Ralpha1 might have functions unrelated to the capacity to form a type II IL-4/IL-13R with IL-4Ralpha.


[DNA concentration in the nuclei of endometrial gland epithelium in the presence of dyshormonal hyperplasias of the climacteric period].
The DNA content in the nuclei of the glandular epithelium of the endometrium was studied by microspectrophotometry in 6 women of fertile age and 10 with the climacteric dyshormonal adenocystic hyperplasia. In normal uterine mucosa the DNA quantity remained unchanged at various phases of the menstrual cycle. As compared to the normal, in dyshormonal endometrial hyperplasia the DNA content was almost doubled; there was also a moderate increase of polyploidy.


Management of uncomplicated total knee arthroplasty chronic pain and stiffness utilizing cooled radiofrequency ablation: a single institution pilot study.
The objective of this study is to introduce cooled radiofrequency ablation technical feasibility as an alternative percutaneous image-guided treatment of chronic pain and stiffness in the setting of uncomplicated total knee arthroplasty. This retrospective pilot study includes a total of 19 consecutive patients experiencing persistent chronic pain after total knee arthroplasty, without underlying hardware complications who had failed conservative care. Patients initially underwent anesthetic blocks of the genicular nerve branches to determine C-RFA candidacy. After adequate response to the anesthetic blocks (> 50% immediate pain relief), patients were subjected to cooled radiofrequency ablations 2-3 weeks later. Treatment response was evaluated utilizing clinically validated questionnaires (KOOS, the Knee Injury and Osteoarthritis Outcome Score) and visual analog scale (VAS) to assess pain severity, stiffness, functional activities of daily living, and use of pain medication. Follow-up outcome scores were collected up to 1 year after C-RFA procedure. A total of 21 knees were treated consecutively between 4/2019 and 1/2020 (mean age 70.5 years; 5 M:14F). The mean total KOOS score improved significantly from baseline at 35.0 ± 14.0 to 64.2 ± 14.7 at a mean of 10.2 months after treatment (p < 0.0001), with significant improvement in mean stiffness score from 44.8 ± 16.7 to 68.8 ± 20 (p < 0.0001). The mean VAS score improved significantly from baseline at 8.30 ± 1.1 to 2.45 ± 1.8 (p < 0.0001). No major complications were encountered. No patients went on to receive re-treatment, surgical revision, or other intervention. Image-guided genicular nerve cooled radiofrequency ablation offers a promising alternative in treating chronic pain/stiffness in the setting of uncomplicated TKA.


Potentiation of neuronal L calcium channels by IGF-1 requires phosphorylation of the alpha1 subunit on a specific tyrosine residue.
Insulin-like growth factor 1 (IGF-1) rapidly potentiates N and L calcium channel currents in cerebellar granule neurons by an unknown mechanism. Here, we show that the L channel alpha1C subunit is tyrosine phosphorylated in response to IGF-1. Moreover, expression of kinase-dead c-Src in neurons or acute block of Src family kinases with a cell-permeable inhibitor specifically blocks L channel potentiation. Purified Src kinase phosphorylates tyrosine residue Y2122 of the C terminus of neuronal alpha1C in vitro, and c- and v-Src directly bind the C terminus. When expressed in neuroblastoma cells, point mutation of Y2122 prevents both tyrosine phosphorylation of alpha1C and IGF-1 potentiation. Our data provide a biochemical mechanism whereby phosphorylation of a single specific tyrosine residue rapidly modifies ion channel physiology.


Functional expression of P2 receptors in the inner ear of chicken embryo.
The purpose of the present study was to investigate the modulation of spontaneous afferent activity by ATP during embryonic development in a preparation isolated chicken inner ear. This work was performed using multiunit and single-unit extracellular recordings from the posterior semicircular canal nerve and the basilar papilla nerve. α,β-meATP, a P2X receptor agonist, notably increased the discharge frequency of the vestibular afferents between E15 and E18, but not in the basilar papilla. In contrast, the P2Y receptor agonist UTP produced a slight increase in the discharge frequency of basilar papilla afferents, without apparent changes in the vestibular afferent activity. 2-MeSATP, a P2Y agonist, increased the basal discharge of the primary afferents in a dose-age dependent way, but when we applied the antagonist of P2Y receptor, Reactive Blue 2 (10(-4)M), the effect of 2-MeSATP decreased significantly. This was observed both in vestibule and basilar papilla. Using RT-PCR the presence of P2X₃, P2Y₁, P2Y₂ and P2Y₆ mRNA was documented in the vestibular system with more important presence during the early stage (E15) than the later stage (E21), however in the basilar papilla we found only the P2Y₁, P2Y₂ and P2Y₆ mRNA with the same temporal course as in the vestibule. These results confirm our pharmacological findings. Together this data suggests a role for P2X receptors-mediated purinergic signaling in vestibular synaptic organization. Temporal changes in P2Y receptors during development might be involved in the establishment of the endolymphatic ion composition needed for normal vestibular and auditory transduction and/or specific cellular differentiation.


Vascular complications after balloon aortic valvuloplasty in recent years: Incidence and comparison of two hemostatic devices.
To define the incidence of vascular complications (VC) after balloon aortic valvuloplasty (BAV) in recent years, and to compare the performance of two vascular closure devices (VCD). VC remain the most frequent drawback of BAV and are associated with adverse clinical outcomes. All BAV procedures performed at 2 high-volume centers over a 6-year period (n = 930) were collected in prospective registries and investigated to assess the incidence of Valve Academic Research Consortium-2 (VARC-2) defined VC. Incidence of life-threatening, major and minor bleeding was also assessed. In-hospital major adverse cardiac and cerebrovascular events (MACCE) rate (composite of in-hospital death, myocardial infarction, TIA/stroke, and life-threatening bleeding) as well as 30-day survival was compared between a suture-mediated closure system and a collagen plug hemostatic device. A 9 Fr arterial sheath was used in most of the patients (84.1%). Vascular closure was obtained with the Angio-Seal in 643 patients (69.1%) and the ProGlide in 287 (30.9%). The overall incidence of major VC was 2.7%, and minor VC 6.6%, without significant differences between groups. The Angio-Seal group was associated with a higher rate of small hematomas (6.9% vs. 3.5%, P = 0.042), whilst blood transfusions were more frequent in the ProGlide group (6.6% vs. 3.5%, P = 0.034). Rates of in-hospital MACCE and 30-day survival were similar. Use of either VCD was not independently associated with major VC. VC rate after BAV is fairly low in experienced centers without major differences between the 2 most used VCD.


Awareness of body dimensions during pregnancy: an analogue study.
Two alternative explanations of the body-image abnormality in anorexia nervosa patients are outlined: namely, the 'abnormal sensitivity' and 'adaptational failure' hypotheses. Evidence relating to these 2 conflicting hypotheses was obtained from body-perception measurements carried out on groups of pregnant women. In the first study 40 pregnant women, at approximately 4 month's duration, were found to overestimate their bodily dimensions, albeit to a lesser extent than the previously tested group of anorexia nervosa patients (Slade & Russell, 1973a). When they were subdivided on the basis of a history of weight change over the previous 12 months, the 'stable weight' subgroup was found to overestimate significantly more than the 'weight gain' and 'weight loss' subgroups. In a second study 16 of the original group of pregnant women were retested at approximately 8 month's duration. Although their weight and bodily dimensions had increased on retesting, their tendency to overestimate was found to be significantly reduced. It was concluded that the phenomenon of body-image disorder is not specific to anorexia nervosa, extending not only to patients with obesity and to some normal women, but also to women during pregnancy. Moreover, the 'abnormal sensitivity' hypothesis was considered to fit these and other recently accumulated data better than the alternative 'adaptational failure' hypothesis. Some of the theoretical and clinical implications of these findings are discussed.


Catecholamines and acetylcholine are key regulators of the interaction between microbes and the immune system.
Recent studies suggest that catecholamines (CAs) and acetylcholine (ACh) play essential roles in the crosstalk between microbes and the immune system. Host cholinergic afferent fibers sense pathogen-associated molecular patterns and trigger efferent cholinergic and catecholaminergic pathways that alter immune cell proliferation, differentiation, and cytokine production. On the other hand, microbes have the ability to produce and degrade ACh and also regulate autogenous functions in response to CAs. Understanding the role played by these neurotransmitters in host-microbe interactions may provide valuable information for the development of novel therapies.


Quantifying temperature and flow rate effects on the performance of a fixed-bed chromatographic reactor.
Chromatographic reactors are based on coupling chemical reactions with chromatographic separation in fixed-beds. Temperature and flow rate are important parameters for the performance of such reactors. Temperature affects mainly adsorption, chemical equilibria, mass transfer and reaction kinetics, whereas flow rate influences residence time and dispersion. In order to evaluate the mentioned effects, the hydrolysis reactions of methyl formate (MF) and methyl acetate (MA) were chosen as case studies. These reactions were performed experimentally in a lab-scale fixed-bed chromatographic reactor packed with a strong acidic ion exchange resin. The chosen reactions can be considered to represent a relative fast (MF) and a relative slow (MA) reaction. The processes which take place inside the reactor were described and simulated using an isothermal equilibrium dispersive model. The essential model parameters were determined experimentally at different temperatures and flow rates. The performance of the chromatographic reactor was evaluated at several discrete constant temperature levels by quantifying product purity, productivity and yield. The work provides insight regarding the influence of temperature and flow rate on values of the model parameters and the performance criteria.


Resistin expression in breast cancer tissue as a marker of prognosis and hormone therapy stratification.
Adipocytokines are adipocyte-derived hormones and well documented to be involved in carcinogenesis. The expression of resistin, a newly discovered adipocytokine, in breast cancer tissues was determined and correlated with patient clinicopathological variables. Resistin expression in breast cancer tissues and the normal adjacent breast tissues was analyzed by immunohistochemistry and was correlated with clinicopathological variables as well as recurrence rates by the chi-square test. The prognostic value of resistin for disease-free and overall survival was determined by Kaplan-Meier estimates, and the significance of differences between curves was evaluated by the log-rank test. High resistin expression was predominantly observed in breast cancer tissues but not the adjacent normal breast tissues. High resistin expression in breast cancer tissues was correlated significantly with tumor stage, tumor size, lymph node metastasis and estrogen receptor status. Hormone therapy, but not radiotherapy or chemotherapy, decreased the recurrence rate in patients with high resistin expression. While high resistin expression was associated with poor disease-free and overall survival, Cox regression analysis also revealed that resistin was an independent predictor of disease-free and overall survival. High resistin expression in breast cancer tissue is associated with a more malignant clinicopathological status as well as poor patient survival. Resistin may therefore hold promise as an independent prognosis predictor for breast cancer, as a marker for hormone therapy stratification and as a potential therapeutic target.


FT-IR spectroscopy and morphological study of functionalized cellulosic fibers: Evaluation of their dyeing properties using biological Pistacia vera hulls by-product extract.
The repulsion between cellulose and anionic entities could be overcome by imparting cationic sites on its structure. In this work, we studied the treatment of cotton fabric with different amounts of chitosan bio-polymer (0.0125-0.075%), dimethyl diallyl ammonium chloride and diallylamin co-polymer (1-5%), alum (0.5-20 g/L), and sodium chloride (2-40 g/L) in order to improve their dyeing behaviors with an ecological extract of Pistacia vera hulls by-products. The chemical modification of the cellulosic fibers was confirmed using Fourier Transform Infra-Red (FT-IR) and Scanning Electron Microscopy (SEM). The unmodified and modified cellulosic samples were, then, dyed with Pistacia vera extract. The dyeing characteristics were assessed through the measurements of the color coordinates and the color strength. Results showed that the dyeing performance followed the order: Cotton-dimethyl diallyl ammonium chloride and diallylamin co-polymer (K/S = 9.6) > Cotton-Chitosan (K/S = 8.97) > Cotton-Alum (8.84) > Cotton-NaCl (K/S = 6.06) > Untreated cotton (K/S = 1.98). All dyed samples exhibited good fastness to washing, rubbing and light. Overall, it has shown in this study that the functionalization of cellulose structure could greatly improve its dyeing behavior depending on the cationic sites number.


Wise-pattern Mastectomy with an Inferior Dermal Sling: A Viable Alternative to Elliptical Mastectomy in Prosthetic Based Breast Reconstruction.
Prosthetic based post-mastectomy breast reconstruction in patients with large or pendulous breasts remains challenging due to inelastic and redundant skin, with various approaches to skin reduction at the time of mastectomy. This study describes our experience with a Wise pattern inferior dermal sling approach to skin sparing mastectomy. Retrospective chart review was performed on patients who underwent immediate prosthetic-based breast reconstruction after mastectomy from 2009 to 2021. Two hundred and forty patients who underwent Wise pattern skin sparing mastectomy (WSSM) were compared to a cohort of patients who had traditional elliptical skin sparing mastectomy (ESSM), matched for mastectomy weight, prior radiation, and smoking. 90-day post-surgical outcomes were examined. The WSSM cohort had significantly higher BMI (30.3 vs 26.9, p < 0.0001) and mastectomy weight (831 g vs 607 g, p < 0.0001). After propensity score matching, there was no significant difference in complication or treatment rates between WSSM and ESSM breasts except for mastectomy flap necrosis (11.6% vs 5.0%, p = 0.0082). WSSM patients who had mastectomy flap necrosis did not have significantly different treatment rates of admission, return to operating room, or explantation compared to ESSM patients. In the largest reported series to date, WSSM was associated with a higher rate of mastectomy flap necrosis, but this did not translate to statistically significant differences in treatment. The inferior dermal flap likely acts as a protective layer of vascularized tissue, which appears to prevent evolution of mastectomy skin flap necrosis into more serious adverse outcomes.


Rethinking the Negativity Bias.
The negativity bias is a broad psychological principle according to which the negative is more causally efficacious than the positive. Bad, as it is often put, is stronger than good. The principle is widely accepted and often serves as a constraint in affective science. If true, it has significant implications for everyday life and philosophical inquiry. In this article, I submit the negativity bias to its first dose of philosophical scrutiny and argue that it should be rejected. I conclude by offering some alternative hedonic hypotheses that survive the offered arguments and may prove fruitful.


A Time to Eat and a Time to Exercise.
This Perspective for Progress provides a synopsis for the potential of time-restricted eating (TRE) to rescue some of the deleterious effects on circadian biology induced by our modern-day lifestyle. We provide novel insights into the comparative and potential complementary effects of TRE and exercise training on metabolic health.


Antimicrobial activity of several antibiotics and a sulfonamide against Chlamydia trachomatis organisms in cell culture.
Minimum inhibitory concentrations of several antibiotics and a sulfonamide for growth of the 15 known immunotypes of Chlamydia trachomatis were determined in HeLa 229 cell cultures. The concentrations for complete inhibition of infectious-organism production were (per milliliter): tetracycline, 0.02 to 0.5 mug; rosamicin, 0.05 to 0.25 mug; erythromycin, 0.1 to 0.5 mug; chloramphenicol, 10 mug; penicillin, 0.02 to 50 U; ampicillin, 0.1 to 50 mug; and sulfisoxazole, 2 to 200 mug. The same concentrations of tetracycline, rosamicin, erythromycin, and chloramphenicol were sufficient to inhibit C. trachomatis inclusion formation. An increased concentration of sulfisoxazole was often needed to inhibit inclusion formation. Penicillin at 100 U/ml and ampicillin at 100 mug/ml failed to completely inhibit inclusion formation.


Uridine prevents the glucose deprivation-induced death of immunostimulated astrocytes via the action of uridine phosphorylase.
We previously reported that in immunostimulated astrocytes, glucose deprivation induced cell death via the loss of ATP, reduced glutathione, and mitochondrial transmembrane potential. The cytotoxicity was due to reactive nitrogen and oxygen species and blocked by adenosine, a purine nucleoside, via the preservation of cellular ATP. Here, we investigated whether uridine, a pyrimidine nucleoside, could prevent the glucose deprivation-induced cytotoxicity in LPS+IFN-gamma-treated (immunostimulated) astrocytes. Glucose deprivation induced the death of immunostimulated cells, which was significantly reduced by uridine. Glucose deprivation rapidly decreased cellular ATP levels in immunostimulated astrocytes, which was also reversed by uridine. The inhibition of cellular uptake of uridine by S-(4-nitrobenzyl)-6-thioinosine attenuated the protective effect of uridine. mRNA and protein expression for uridine phosphorylase, an enzyme catalyzing reversible phosphorolysis of uridine, were observed in rat brain as well as primary astrocytes. 5-(Phenylthio)acyclouridine (PTAU), a specific inhibitor of uridine phosphorylase, inhibited the protective effect of uridine. Additionally, the loss of mitochondrial transmembrane potential and reduced glutathione by glucose deprivation in immunostimulated cells was attenuated by uridine, which was also reversed by PTAU. These results provide the first evidence that uridine protects immunostimulated astrocytes against the glucose deprivation-induced death by preserving intracellular ATP through the action of uridine phosphorylase.


Decreased carbonyl reductase 1 expression promotes malignant behaviours by induction of epithelial mesenchymal transition and its clinical significance.
Human carbonyl reductase 1 (CBR1) is an enzyme that catalyse the reduction of many compounds by using NADPH-dependent oxydoreductase activity. Although CBR1 is known to regulate the tumour progression, the molecular mechanisms of CBR1 in cancer progression and the clinical significance of CBR1 status remain unclear. Here, we investigated the molecular mechanisms by which CBR1 affects cancer cell behaviour in vitro and the clinical significance of CBR1 using immunohistochemical analyses in endometrial cancer. Here, the role of CBR1 in cancer cell invasion and metastasis, and its molecular mechanisms were investigated by transfection of sense and antisense CBR1 cDNAs into a human endometrial adenocarcinoma cell line. The relationship between CBR1 expression analysed by immunohistochemistry and prognosis such as progression free survival (PFS) and overall survival (OS) was examined in endometrial cancer tissues from FIGO stage I-IV (n=109). Suppression of CBR1 by antisense CBR1 cDNA increased cancer cell invasion, and suppressed E-cadherin expression and capacity for cellular aggregation. In contrast, over-expression of CBR1 by sense CBR1 cDNA increased E-cadherin expression and capacity for cellular aggregation, and suppressed cancer cell invasion. The expression of transcriptional suppressors of E-cadherin, Snail and ZEB1, were increased by CBR1 suppression, but suppressed by CBR1 over-expression. Immunohistochemical analyses showed that decreased CBR1 expression is significantly related with poor PFS and OS compared with strong CBR1 expression. In multivariate analyses, decreased CBR1 expression was an independent prognostic factor for PFS and OS. CBR1 regulates cancer cell invasion in endometrial adenocarcinomas by regulating the epithelial mesenchymal transition. A decreased CBR1 expression can be a useful marker of an unfavourable clinical outcome in patients with endometrial cancer.


The Ethyl Acetate Extract of the Marine Edible Gastropod Haliotis tuberculata coccinea: a Potential Source of Bioactive Compounds.
The phylum Mollusca represents one of the largest groups of marine invertebrates. Nowadays, molluscan shellfish belonging to the classes Bivalvia and Gastropoda are of commercial interest for fisheries and aquaculture. Although bioactive properties of bivalve molluscs have been widely investigated and several dietary supplements have been brought to the market, the bioactive potentialities of marine gastropods are poorly documented. The present study investigated the bioactive properties of tissue extracts derived from Haliotis tuberculata coccinea, or "European abalone," an edible abalone species distributed in the Mediterranean Sea and the northeast Atlantic Ocean. A bioactive organic compound-rich extract was obtained using ethyl acetate as extracting solvent. It showed antimicrobial activity towards the methicillin-resistant Staphylococcus epidermidis strain RP62A, the emerging multi-drug-resistant Stenotrophomonas maltophilia D71 and Staphylococcus aureus ATCC 6538P, being the most sensitive strain. It also showed anthelmintic activity, evaluated through the toxicity against the target model helminth Caenorhabditis elegans. In addition, the ethyl acetate extract demonstrated a selective cytotoxic activity on the cancer cell lines A375, MBA-MD 231, HeLa, and MCF7, at the concentration of 250 µg/mL. The fatty acid composition of the bioactive extract was also investigated through FAME analysis. The fatty acid profile showed 45% of saturated fatty acids (SAFA), 22% of monounsaturated fatty acids (MUFA), and 33% of polyunsaturated fatty acids (PUFA). The presence of some biologically important secondary metabolites in the extract was also analysed, revealing the presence of alkaloids, terpenes, and flavonoids.


Retrievability of Thermafil plastic cores using organic solvents.
Twenty distal roots of extracted mandibular first and second molars were instrumented, then obturated using Thermafil obturating material with solid plastic core carriers. To simulate a retreatment process, the gutta-percha was softened using one of four solvents, chloroform, xylene, eucalyptol, or halothane. A K file was used to advance the solvent into the gutta-percha and to engage the plastic carrier. In all but one case, the plastic carriers were easily removed from the root canal. It was concluded that the plastic carriers used with the Thermafil obturation media do not present a difficult obstacle for removal should the root require retreatment.


Structural and functional imaging by MRI.
Magnetic resonance imaging is one of the most exciting techniques for noninvasive molecular imaging of the cardiovascular system. The article will describe challenges, solutions and results of magnetic resonance plaque imaging ex-vivo, in the experimental animal and in patients.


New insights to the potential mechanisms driving coronary flow reserve impairment in Cushing's syndrome: A pilot noninvasive study by transthoracic Doppler echocardiography.
The contribution of functional and/or structural remodeling to reduced coronary flow velocity reserve (CFVR), reflecting impaired coronary microcirculation in Cushing's syndrome (CS), has not been clearly elucidated. We aimed to identify the potential mechanisms of coronary microvascular impairment in CS. We studied 15 CS patients (11 female, age 50 ± 9 years) without clinical evidence of cardiovascular disease. Coronary flow velocity in the left anterior descending coronary artery was measured by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. Average peak flow velocities, CFVR, and microvascular resistance in baseline (BMR) and hyperemic conditions (HMR) were assessed. CFVR ≤2.5 was considered a marker of microvascular disease (CMD). Diastolic function (E/e'), global longitudinal strain (GLS) and fractional pulse pressure (fPP), an index of arterial stiffness, were also assessed. CMD was present in 5 patients (33.3%). CMD was primarily driven by increased baseline peak flow velocity (29 ± 12 versus 19.6 ± 4.2 cm/s, p = .03) in the presence of decreased BMR (3.62 ± 0.6 versus 5.46 ± 1.4 mm Hg·s/cm, p = .03). Moreover, urinary cortisol and E/e' were higher (p = .001 and p = .001, respectively) and GLS was lower (p = .009) in patients with CMD. fPP was higher in patients with CMD (p = .01). Urinary cortisol correlated to CFVR (p = .008), E/e' (p < .0001) and GLS (p < .0001). fPP directly correlated to average peak flow velocities at rest (p = .01) and inversely to BMR (p = .03). Functional microvascular regulatory impairment seems to be the potential mechanism of CMD in CS. CMD seems to be related to decreased myocardial contractility and diastolic dysfunction associated with cortisol excess.


Effect of modern cement technique on acetabular fixation total hip arthroplasty. A retrospective study in matched pairs.
The modern cement technique has significantly reduced the bone-cement interface radiolucency and, therefore, it is suggested that the results of the cemented socket with this technique should be the basis for comparison with other methods of fixation.


Safety of direct true lumen cannulation after venous exsanguination: a study in a surviving porcine model†.
Type A aortic dissection requires immediate surgery. Traditional cannulation methods such as the central aortic cannulation with the Seldinger technique and axillary cannulation are primary choices. Yet in the presence of tamponade or severe cardiogenic shock, these can be too time-consuming to complete. Direct true lumen cannulation after venous exsanguination not only avoids this issue but also leads to transient global ischaemia. We studied the safety of direct true lumen cannulation from the aspect of global ischaemia in a surviving porcine model. Twelve pigs were randomized to either control or intervention groups (6 + 6). The intervention group underwent simulated direct true lumen cannulation by exsanguination and circulatory arrest for 5 min at 35°C before cardiopulmonary bypass (CPB). Both groups underwent CPB cooling to 25°C followed by a 25-min arrest period and subsequent warming to 36°C. Neuron-specific enolase levels were measured at 6 time-points from blood samples. Near-infrared spectroscopy was used to determine brain oxygenation. The neurological recovery was evaluated daily during a 7-day follow-up, and the brain was harvested for a histopathological analysis after euthanization. All pigs recovered their normal neurological behaviour. The neurobehavioural total score on postoperative day 2 reached borderline statistical significance, thus favouring the intervention group [(9 (8.75-9) vs 6.5 (5.5-9), P = 0.06]. Near-infrared spectroscopy values and neuron-specific enolase levels slightly favoured the control group during the cooling period, but the difference was not clinically significant. The histopathological analysis showed no difference between the groups. A 5-min period of normothermic global ischaemia before CPB does not impair the neurological outcome following hypothermic circulatory arrest in a surviving porcine model.


Determinants of blood donation willingness in the European Union: a cross-country perspective on perceived transfusion safety, concerns, and incentives.
Willingness to donate blood depends on personal characteristics, beliefs, and motivations, but also on the cultural context. The aim of this study was to examine whether willingness to donate blood is associated with attitudes toward blood transfusion, personal motivators, and incentives and whether these factors vary across countries in the European Union (EU). The sample consisted of 27,868 participants, from 28 EU member states, who were interviewed about blood donation and transfusion-related issues for the 2014 round of the Eurobarometer, a country-comparative survey, collected on behalf of the European Commission. Participants were asked whether they would be willing to donate blood and for which reasons (motivators) and which incentives are appropriate to receive in return for a blood donation. Willingness to donate varied significantly across countries and was positively associated with perceived blood transfusion safety. Furthermore, helping family or people in need were the most powerful motivators for blood donation willingness in almost all countries. In contrast, the number of participants who were willing to donate to alleviate shortages or to contribute to research varied widely across countries. The wish to receive certain incentives, however, did not seem to be related to willingness to donate. Perceived blood transfusion safety and personal motivations may be stronger determinants of willingness to donate than receiving certain incentives. EU-wide strategies and guidelines for donor recruitment and retention should take both overall and country-specific patterns into account. For example, education on the importance of donation could be considered.


[Seringueira's latex membrane (Hevea brasiliensis) with and without polylysine 0.1% and marlex mesh for the reconstruction of iatrogenics abdominal wall defects in rats].
To compare seringueira latex membrane implant, with and without polylysine at 0.1% and marlex mesh on the repair of iatrogenic abdominal defects in rats. A circular segment block of approximate three centimeters of diameter was sectioned out of the ventral abdominal muscle wall of 31 Wistar rats. The skin was preserved. The animals were divided into three experimental groups: only latex, latex and polylysine at 0.1%, and marlex mesh. Some rats underwent euthanasia at five and some at 120 days after surgery. Fragments of abdominal wall were collected and submitted at histopathologic analysis. The main alterations observed in groups treated with the latex membrane with and without polylysine were dehiscence (21 animals) and evisceration (two animals). The elimination of implant occurred at an average of 13.8 days. These animals presented fiber conjunctive tissue formation, similar to that observed in the group which received the marlex mesh. Other alterations noted were viscera-parietal adherences in all evaluated groups. The seringueira' s latex membrane, with or without polylysine 0.1%, when used on the reconstruction of abdominal defects in rats is eliminated at 13.8 days after its implantation, leaving a fiber base of reparation, similar to that observed after marlex mesh implantation.


Representational momentum reveals visual anticipation differences in the upper and lower visual fields.
Recent empirical research has revealed differences in functional capacity between the upper and lower visual fields (VFs), with the lower VF exhibiting superiority in visual perception skills. Similarly, functional differences between the left and right hemispheres elicit a predominance for visuospatial processing in the left visual field (left VF). Both anatomical as well as evolutionary arguments have been adopted in accounting for these variations in function. Preceding upper and lower VF research has typically investigated either static stimulus perception or the visual processing of upper limb action. The aim of the current research was to investigate whether the lower VF benefits associated with limb control transcend to visual anticipation (the perception of motion). Methods were based on Khan and Lawrence (Exp Brain Res 164:395-398, 2005), who investigated upper/lower VF differences in visuomotor control, but utilising a representational momentum paradigm to isolate perceptual processes. Thirty-two participants were randomised into either a left or right VF group and completed a perceptual computer-based task in the upper and lower VF, where they were required to judge the final position of a moving object before it disappeared. Two aspects of the distributions of same responses were then analysed; the central tendency (weighted means) and the variability. Results revealed that in the left VF, weighted means for the lower VF were significantly greater than for the upper VF [t(14) = 2.242, p = 0.042]. In both left and right VFs, variability was greater in the upper compared to lower VF. This provides new findings regarding visual processes in the different visual fields. While visual search and large scene perception has been found to be superior in the upper VF, here we find that visual anticipation, like target-directed visuomotor skill, is superior in the lower VF.


Structural connectomics of anxious arousal in early adolescence: Translating clinical and ethological findings.
Etiological explanations of clinical anxiety can be advanced through understanding the neural mechanisms associated with anxiety in youth prior to the emergence of psychopathology. In this vein, the present study sought to investigate how trait anxiety is related to features of the structural connectome in early adolescence. 40 adolescents (21 female, mean age = 13.49 years) underwent a diffusion-weighted imaging scan. We hypothesized that the strength of several a priori defined structural connections would vary with anxious arousal based on previous work in human clinical neuroscience and adult rodent optogenetics. First, connection strength of caudate to rostral middle frontal gyrus was predicted to be anticorrelated with anxious arousal, predicated on extant work in clinically-diagnosed adolescents. Second, connection strength of amygdala to rostral anterior cingulate and to medial orbital frontal cortex would be positively and negatively correlated with anxious arousal, respectively, predicated on rodent optogenetics showing the former pathway is anxiogenic and the latter is anxiolytic. We also predicted that levels of anxiety would not vary with measures of global network topology, based on reported null findings. Results support that anxiety in early adolescence is associated with (1) the clinical biomarker connecting caudate to frontal cortex, and (2) the anxiogenic pathway connecting amygdala to rostral anterior cingulate, both in left but not right hemisphere. Findings support that in early adolescence, anxious arousal may be related to mechanisms that increase anxiogenesis, and not in a deficit in regulatory mechanisms that support anxiolysis.


Inflammatory cytokines as an underlying mechanism of the comorbidity between bipolar disorder and migraine.
A bi-directional association between mood disorders and migraine has been consistently reported. Nevertheless, the neurobiological substrate underlying the association between these disorders remains unknown. In the article herein we review evidence for the role of inflammatory cytokines in the neurobiology of bipolar disorder and migraine. In addition, inflammation is hypothesized to be a shared pathophysiological mechanism subserving the bipolar disorder and migraine concomitance. A derivative of this hypothesis is that pharmacological treatments primarily targeting the inflammatory system may have symptom suppressing effects in bipolar disorder.


Phantosmia Among Pediatric, Adolescent, and Young Adult Patients Receiving Proton Beam Therapy.
Phantosmia, an underreported toxicity of brain radiation therapy (RT), is defined as an olfactory disorder resulting in a malodorous phantom smell. This study aimed to characterize the incidence of phantosmia in patients treated with intensity modulated proton therapy (IMPT). In this institutional review board-approved retrospective study, the electronic medical record of a pencil beam scanning-only proton center was queried for patients ≤39 years of age who received IMPT for primary intracranial, metastatic intracranial, skull base, nasopharyngeal or sinonasal neoplasms between August 2019 and December 2020. Patient, clinical, and phantosmia-related characteristics were collected. The olfactory region was defined to include the olfactory bulb and tract. Phantosmia severity was graded by intervention use (mild, no intervention; moderate, supportive treatment; severe, RT discontinuation). Ninety-nine patients met the inclusion criteria. Twelve patients (12.1%) reported phantosmia. Patients described perceiving a "chlorine," "broccoli," "stale water," "metallic," or "noxious" smell. Of the patients who reported phantosmia, median age was 17 (12-33) years, 66.7% were male, and 91.7% had intracranial tumors. None of the patients had prior RT. Chemoradiotherapy treatment did not correlate with phantosmia development (odds ratio, 1.09; 95% confidence interval, 0.32-3.70; P = .90). Ten patients experienced accompanying toxicities, including taste changes (n = 3), vision disturbances (n = 5), and nausea/emesis (n = 7). Phantosmia was mild (n = 7) or moderate (n = 5). All patients completed their RT course. Sixty-seven percent received craniospinal irradiation (CSI) while 33% received focal brain RT, with the olfactory region receiving doses as low as 0.5 Gy. Notably, 8 of 27 patients who received CSI (30%) reported phantosmia (odds ratio, 7.66; 95% confidence interval, 2.07-28.34; P = .002). In the first-ever study examining radiation-induced phantosmia among children and young adults treated with IMPT, all affected patients received irradiation dose to the olfactory region. Physician awareness of phantosmia, especially in the context of CSI, may improve the patient experience and treatment compliance. A prospective study is needed to elucidate frequency, severity, and phantosmia mechanism.


Unveiling the impact of the light-source and steric factors on [2+2] heterocycloaddition reactions.
Information gained from in-depth mechanistic investigations can be used to control the selectivity of reactions, leading to the expansion of the generality of synthetic processes and the discovery of new reactivity. Here, we investigate the mechanism of light-driven [2+2] heterocycloadditions (Paternò-Büchi reactions) between indoles and ketones to develop insight into these processes. Using ground-state UV-Vis absorption and transient absorption spectroscopy (TAS), together with DFT calculations, we found that the reactions can proceed via an exciplex or electron-donor-acceptor (EDA) complex, which are key intermediates in determining the stereoselectivity of the reactions. We used this discovery to control the diastereoselectivity of the reactions, gaining access to previously inaccessible diastereoisomeric variants. When moving from 370 to 456 nm irradiation, the EDA complex is increasingly favoured, and the diastereomeric ratio (d.r.) of the product moves from >99:<1 to 47:53. In contrast, switching from methyl to ipropyl substitution favours the exciplex intermediate, reversing the d.r. from 89:11 to 16:84. Our study shows how light and steric parameters can be rationally used to control the diastereoselectivity of photoreactions, creating mechanistic pathways to previously inaccessible stereochemical variants.


Pseudo tumors of the lung after lung volume reduction surgery.
We describe 2 patients who underwent lung volume reduction surgery, who postoperatively had computed tomographic scans that showed symptomatic mass lesions suggestive of malignancy and an inhaled foreign body. Investigations excluded these conditions with the remaining likely diagnosis of pseudotumor secondary to buttressing material. These potential sequelae of lung volume reduction surgery should be recognized in follow-up investigations.


Magic of the touch.
The article highlights the impact of physician's touch on the patient's psyche and healing process and more importantly, vice-versa. Not infrequently, this 'small' aspect is overlooked by the physicians but on deeper analysis, this 'small' gesture has profound impact on the patients as well as the physicians.


Predictors of follow-up non-compliance after definitive radiotherapy for locally advanced cervical cancer at a community cancer center.
Non-compliance to post-treatment cancer surveillance can lead to late detection of recurrence. This study aims to identify patients at high risk for loss of follow-up after radiotherapy for locally advanced cervical cancer. Consecutive patients with locally advanced cervical cancer treated with definitive chemoradiotherapy (2013-2020) at a community cancer center were retrospectively reviewed. The main outcome was overall follow-up compliance rate over time. Additionally, specialist-specific follow-up times, reasons for discontinuation and predictors of loss of follow-up events were evaluated. The median age of the 154 patients included was 46.5 years (range: 26-84). The 6-month, 1-, 3-, and 5-year overall loss of follow-up rates were: 5.3%, 15.3%, 33.6%, and 48.2%, respectively. After a median overall follow-up time of 21.0 months, the median specialist-specific surveillance times were 17 months and 6 months with gynecologic and radiation oncologists, respectively (p < 0.01). Overall, the most common reasons for loss of follow-up were financial (21.7%) and relocation to another city (28.3%). By specialty, the most common reasons were relocation of care (56.5%, gynecologic oncologist) and disease progression (31.3%, radiation oncologist). In the multivariable analysis, older age (continuous, OR: 0.96; p < 0.01) and Hispanic ethnicity (OR: 0.39; p < 0.01) were protective against loss of follow-up, while increased number of gestations (continuous, OR: 1.23, p = 0.01) and living farther from the cancer center (continuous, OR: 1.002; p = 0.03) increased the chance of loss of follow-up. Younger, non-Hispanic, multiparous women that live far from the community cancer center have an increased chance of follow-up discontinuity, which are attributed to financial reasons in more than 20% of the cases.


[Dependence of cordycepin inhibition of heterogeneous nuclear RNA biosynthesis in rat brain on the size of the poly(A) segments].
A study was made of the effect of cordicepin on the biosynthesis of rat brain heterogeneous nuclear RNA (hnRNA) fractions, such as poly(A-)hnRNA, oligo(A+)hnRNA and poly(A+)hnRNA differing in the size of poly(A)-segments. Cordicepin was shown to inhibit the biosynthesis of poly(A+)hnRNA alone. However, small doses of the antibiotic do not virtually inhibit the biosynthesis of hnRNA with shorter segments of poly(A). At the same time they inhibit the biosynthesis of hnRNA containing long chains of poly(A) in the 3'-end. A possible molecular mechanism of the phenomenon reviewed is under discussion.


Static and dynamic fusimotor interaction and the possibility of multiple pace-makers operating in the cat muscle spindle.
The interaction of static and dynamic fusimotor activation on the firing of primary muscle spindle afferents has been studied in the cat soleus muscle at constant length and during sinusoidal stretching. Cycle histogram analysis revealed summation of static and dynamic action during the peak of the afferent response to sinusoidal stretching, while static action completely occluded the dynamic effect during the trough of the response. Occlusion was complete as long as, for single fusimotor activation, the static-induced trough response exceeded the dynamic-induced one by about 25%. The investigation of inter-spike interval distributions obtained at constant muscle length revealed occlusion of dynamic by static action in 8 out of 13 cases. A model of multiple spike generation in primary spindle afferents is considered which is based on two or more pacemakers arranged in parallel, with a common pacemaker in series.


Predictors of general and health-related quality of life in Parkinson's disease and related disorders including caregiver perspectives.
Our understanding of the determinants of quality of life (QOL) in people living with Parkinson's disease and related disorders (PDRD) has grown remarkably in the past decade. However, several areas remain understudied including determinants of general vs. health-related QOL, determinants in high-need patients, drivers of perceptions of caregivers vs. patients, and exploration of potential determinants outside of the traditional medical model. This was a cross-sectional study of 210 PDRD patients and 175 caregivers who completed a battery of measures regarding general QOL (QOL-Alzheimer's disease; QOL-AD), health-related QOL (Parkinson's disease Questionnaire; PDQ-39), cognitive function, mood, grief, spiritual wellbeing, symptom burden, disease severity, disease stage, overall function, socioeconomic status, and healthcare utilization. Elastic net regularization modeling of variables significantly associated with our outcomes of interest were performed to determine predictors of general QOL, compare predictors of general vs. health-related QOL, and compare predictors of patient and caregiver perspectives on patient general QOL. General QOL was associated with spiritual wellbeing, depression, cognitive function, presence of a caregiver, and recent emergency department visits. In contrast, health-related QOL was associated with grief, symptom burden, income, disease stage, and utilization of counseling services. Caregiver ratings of patient general QOL were associated with patient symptom burden, patient grief, patient global function, caregiver burden, and caregiver spiritual wellbeing. There are notable differences in the predictors of general QOL, health-related QOL and caregiver perspectives on patient general QOL. These differences have important implications for clinical research and models of clinical care.


Modulation of venom-induced leukocyte histamine release by mononuclear cells: effect of venom immunotherapy.
Leukocyte histamine release and blood mononuclear cell proliferative responses to venoms were evaluated in nine patients with sting anaphylaxis. The effect of venom-activated mononuclear cells on the autologous mononuclear cell proliferative response and venom-induced leukocyte histamine release was also studied before and on maintenance immunotherapy. The mononuclear cell proliferative response was low (specific incorporations less than 2.0) and antigen nonspecific both before and during maintenance immunotherapy. Venom-induced in vitro leukocyte histamine release did not change significantly with immunotherapy. However, when patients were on maintenance immunotherapy, venom-activated mononuclear cells cocultured with autologous leukocytes significantly (p less than 0.05) suppressed venom-induced histamine release. The suppressive effect of mononuclear cells was antigen specific and enhanced by in vitro mononuclear cell activation. Suppression of leukocyte histamine release by mononuclear cells extends the regulatory potential of these cells and may identify an additional mechanism by which immunotherapy protects Hymenoptera-sensitive individuals against systemic anaphylaxis.


Baseline salivary cortisol levels and preconscious selective attention for threat. A pilot study.
This study was conducted to examine the relationship between baseline salivary cortisol (CORT) levels and selective attention for displays of angry faces. Selective attention was investigated using a pictorial emotional Stroop task, comparing colournaming-speed of angry and neutral faces. The task was assessed in supraliminal (unmasked) and subliminal (masked) conditions to 28 non-clinical subjects (14 male and 14 female). Repeated measures analysis of variance revealed a significant interaction between median split CORT levels (low vs. high) and masked face valence (angry vs. neutral). The latter effect was mainly due to significant facilitation in the high CORT subject-group; these subjects seemed to allocate their attention away from the masked angry face. A relation between baseline CORT levels and fast withdrawal behavior is suggested.


Occurrence, environmental implications and risk assessment of Bisphenol A in association with colloidal particles in an urban tropical river in Malaysia.
Phase distribution of emerging organic contaminants is highly influential in their presence, fate and transport in surface water. Therefore, it is crucial to determine their state, partitioning behaviour and tendencies in water environments. In this study, Bisphenol A was investigated in both colloidal and soluble phases in water. BPA concentrations ranged between 1.13 and 5.52 ng L-1 in the soluble phase and n.d-2.06 ng L-1 in the colloidal phase, respectively. BPA was dominant in the soluble phase, however, the colloidal contribution ranged between 0 and 24% which implied that colloids can play a significant role in controlling BPA's transportation in water. Urban and industrial areas were the main sources of BPA while forest areas displayed lower levels outside the populated domains. pH levels were between 6.3 and 7.4 which might have affected BPA's solubility in water to some extent. The particle size distribution showed that the majority of the particles in river samples were smaller than 1.8 µm in diameter with a small presence of nanoparticles. Zeta potential varied between - 25 and - 18 mV, and these negative values suggested instability of particles. Furthermore, BPA was positively correlated with BOD, COD and NH3-N which might indicate that these organic compounds were released concurrently with BPA. RQ assessment showed low levels of risk towards algae and fish in the study area.


Improving the prognosis of pediatric Hodgkin lymphoma in developing countries: a Moroccan Society of Pediatric Hematology and Oncology study.
The event-free survival (EFS) of children with Hodgkin lymphoma (HL) exceeds 80% in high income countries (HIC), but little is known about this rate in developing countries. A prospective national protocol for children with classical HL was implemented in Morocco to increase EFS by careful risk stratification, providing each cycle of therapy on time, decreasing treatment abandonment, improving communication among healthcare providers, and improving data collection. Patients were stratified into a favorable risk group (Ann Arbor stages I and II, no B symptoms, no bulky disease, and no contiguous (E) lesions) and received four cycles of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) or an unfavorable risk group (all others) who received two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) and four cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP). All patients received involved-field radiotherapy 25.5 Gy after completion of chemotherapy. EFS was calculated counting death, relapse/resistant disease, and abandonment as events. From February 2004 to December 2007, 160 patients enrolled; 138 (86%) had unfavorable risk features. Twenty patients (12.5%) abandoned treatment, 16 relapsed or had resistant disease, and 6 died (3 unexplained, 2 varicella, and 1 suicide). The estimated 5-year EFS was 70 ± 4% and overall survival 88 ± 3%. Good outcomes for pediatric HL patients can be achieved in LMIC using a multidisciplinary team approach, uniform protocol-based therapy, twinning partnership among oncology units in-country and abroad, and a data collection system to monitor compliance and identify gaps in care.


Greater than predicted decrease in resting energy expenditure with age: cross-sectional and longitudinal evidence.
To determine whether the age-related decrease in resting energy expenditure (REE) is explained by variations in body composition. In Study 1, adult subjects (20-70 years) from the Quebec Family Study were classified into five different age groups. Body composition was measured by hydrodensitometry to determine fat mass and fat-free mass as predictors of REE. In the youngest group of individuals these predictors were used to plot a reference regression that was then used to predict REE in the other age groups. In Study 2, this issue was investigated in a longitudinal design (6-year follow-up). Subjects were subdivided into three groups and a reference regression was plotted at the beginning of the follow-up and was then used to predict REE 6 years later in the three age groups. In Study 1, 627 adults (288 men and 339 women), aged between 20 and 70 years. In Study 2, 191 adults (93 men and 98 women). In Study 1, measured REE was 329, 302, 528 and 636 kJ/day (P < 0.0001) below predicted REE at 34, 44, 54 and 64 years, respectively. In Study 2 the most marked deviation from predicted REE in response to the 6-year follow-up in men was observed in young adults (-548 kJ/day, P < 0.001) while in women, the largest deviation occurred later in life (-720 kj/day, P < 0.001). Aging is accompanied by a decrease in REE that is significantly greater than what is predicted by variations in body composition. This decrease may reach a mean level of about 500-800 kj/day.


Synthesis of α,α-Disulfenylated Aldehydes via Oxidative Transformation of Tertiary Amines.
A method for the copper-catalyzed regioselective β-functionalization of tertiary amines with thiophenols has been developed. The control experiments and primary studies show that a thiyl radical is involved in the reaction, and the method provides a novel and direct approach to synthesize C(sp(3))-S bonds without a directing group under ligand-free conditions.


Assessing olfaction in the Italian population: methodology and clinical application.
Disorders of the sense of smell are receiving growing clinical as well as experimental attention. Indeed, several neurological conditions have been associated with peripheral or central deficits of the olfactory system. In recent years, particular emphasis has been attributed to the early and severe olfactory impairment in neurodegenerative diseases, such as Alzheimer's dementia and Parkinson's disease. Olfactory assessment has also been included in comprehensive pre- and post-surgical evaluations of temporal lobe epilepsy. Moreover, the request for standardized methods of olfactory evaluation by forensic and occupational medicine is greatly increasing. Despite this requirement, there is no agreement in the Italian neurological community on olfactory assessment. This lack prompted us to generate a battery of standardized tests capable of bypassing cross-cultural differences in olfactory assessment and to be potentially useful in the clinical as well as experimental settings. Procedures of assessment of olfactory acuity (detection threshold), identification (multiple choice odor naming), discrimination (differentiation between similar/dissimilar odorants) and memory (recognition of a substance previously smelled) are fully described. In order to control bias factors depending upon the nature of the investigated disorder and the applied olfactory tasks, a minimal complementary neuropsychological assessment is recommended.


State initiatives on prescription drugs: creating a more functional market.
In response to unrelenting increases in prescription drug spending and use, many states are developing and implementing innovative policy solutions. The Reforming States Group (RSG), a nonpartisan organization of senior executive and legislative leaders from more than forty states and provinces formed in 1992, proposes a series of actions to improve the functioning of this market by introducing more explicit information on quality, effectiveness, and price and by experimental waiving of federal regulations.


Histone variant H3.3 maintains adult haematopoietic stem cell homeostasis by enforcing chromatin adaptability.
Histone variants and the associated post-translational modifications that govern the stemness of haematopoietic stem cells (HSCs) and differentiation thereof into progenitors (HSPCs) have not been well defined. H3.3 is a replication-independent H3 histone variant in mammalian systems that is enriched at both H3K4me3- and H3K27me3-marked bivalent genes as well as H3K9me3-marked endogenous retroviral repeats. Here we show that H3.3, but not its chaperone Hira, prevents premature HSC exhaustion and differentiation into granulocyte-macrophage progenitors. H3.3-null HSPCs display reduced expression of stemness and lineage-specific genes with a predominant gain of H3K27me3 marks at their promoter regions. Concomitantly, loss of H3.3 leads to a reduction of H3K9me3 marks at endogenous retroviral repeats, opening up binding sites for the interferon regulatory factor family of transcription factors, allowing the survival of rare, persisting H3.3-null HSCs. We propose a model whereby H3.3 maintains adult HSC stemness by safeguarding the delicate interplay between H3K27me3 and H3K9me3 marks, enforcing chromatin adaptability.


The occurrence of lipid droplets in the proximal and distal tubules of the rat kidney after folic acid treatment.
Folic acid in high doses gives rise to an accumulation of lipid droplets in the kidney in addition to other changes in the epithelial of both proximal and distal tubules. With the administration of methionine a decrease of lipid droplets and an improvement of the structures of most of the membranes and mitochrondria are observed. These findings have been discussed in regard to the theory of the "chemically induced hyperplasia of the kidneys" related to folic acid.


Malignant schwannoma of the upper mediastinum originating from the vagus nerve.
Malignant schwannoma of the upper mediastinum originating from the vagus nerve is extremely rare. A 46-year-old female was admitted for a left cervical mass which was associated with both hoarseness and Horner's syndrome. Chest computed tomography showed a mass extending from the left upper mediastinum to the left supraclavicular area. A fine needle aspiration cytological examination suggested primary lung cancer stage IIIB large cell carcinoma. After administering induction chemo-radiotherapy, a complete surgical resection was performed. The tumor was found to involve both the left vagus nerve and the left sympathetic nerve. Histological examination of the resected specimen revealed the tumor to be malignant schwannoma. Despite incorrect preoperative diagnosis, the multimodality treatment administered in this case, including induction chemo-radiotherapy and surgery, proved to be effective.


Effusion fluid cytology and COVID-19 infection.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID-19), is known to cause severe respiratory infections with occasional accompanying pleural effusion (PE), pericardial effusion (PCE), or peritoneal effusion (PTE). The effect of COVID-19 on effusion cytology is not yet known. This study aimed to examine the cytomorphologic features and workup of effusion fluids in patients with active COVID-19 infection versus those in recovery. PE (n = 15), PCE (n = 1), and PTE samples (n = 20) from hospitalized patients with a SARS-CoV-2 infection (from June 1, 2020, to December 30, 2020) were reviewed. Effusion fluids with metastatic carcinoma were excluded. Differential cell counts, cytomorphology, and relevant immunostains for effusion fluids were retrospectively evaluated and compared between patients with active infection (positive on a SARS-CoV-2 nucleic acid amplification test [NAAT] within 2 months; n = 23) and those in the recovery phase from COVID-19 (negative on a SARS-CoV-2 NAAT for >2 months; n = 13). The cytology diagnoses were negative for malignancy (n = 31), atypical (n = 4), and suspicious for malignancy (n = 1). Active infection cases showed more atypical mesothelial cells than recovery cases (P < .05); some had enlarged nuclei, prominent nucleoli, occasional multinucleation, and bizarre nuclei. Immunostains were performed more often in active infection cases than recovery cases (47.8% vs 7.7%; P < .05). Differential cell counts (available for 28 cases) showed no significant differences between the active infection and recovery groups. This study found atypical and bizarre mesothelial cells more often in effusions of cases with active COVID-19 infection in comparison with patients in recovery. It is important for cytopathologists to become familiar with the cytomorphologic effects of SARS-CoV-2 on effusion cytology so that these cases can be properly triaged.


A case for critical ethnography: rethinking the early years of the AIDS epidemic in South Africa.
The epidemic of AIDS in South Africa has been characterized not only by its rapid progression but also its impassioned controversies. Retrospectively examining a long-term anthropological project and discussing some reactions it elicited, the paper proposes a defense and illustration of a critical ethnography at three moments of the research. Ethnography is first discussed as fieldworks, proposing an alternative to the horizontal multi-sited approach via a vertical multi-layered method using various scales and locations, and thus connecting the disease endured by patients in townships and former homelands with the heated debates in scientific and political forums: this procedure substitutes a political economy of the disease for its cultural and behavioral interpretations. Ethnography is then discussed as writing, suggesting acknowledgment of the social intelligence of the agents as well as the need for a scientific distance: this principle allows the articulation of the objective historical condition of the individuals and their subjective experience of history, both revealed in the development of the epidemic. Ultimately ethnography is considered from the perspective of its afterlife, that is, the continuous process of its translation by readers and commentators, on the one hand, by the author trying to reach beyond the boundaries of the academic realm, on the other, the work of anthropology appearing as a living object open to public conversation and consequently a resource for knowledge and action.


Comparison of the dried properties of Ganoderma lucidum produced by the convective dryer and infrared dryer.
Ganoderma lucidum is a promising medicine with a high amount of antioxidants and calcium. The selection of appropriate drying process methods in food science has a chief role to reach the best final characteristics. This study aimed to investigate the effects of air velocity and temperature in the convective dryer, sample distance, and infrared power in infrared dryers on the drying kinetics and quality of Ganoderma lucidum slices. In addition, Response Surface Methodology based on central composition design was used to optimize and analyze drying conditions. The ranges of temperature and air velocity were 40-60 °C and 0.5-1.5 m/s, respectively in the convective drying process while the range of distance and infrared power was 4-16 cm and 500-1500 W, respectively in the infrared drying process. It is worth mentioning that antioxidant and calcium contents were greatly enhanced during the drying procedures. Moreover, the values of the total color difference ranged between 8.21 and 19.66 for the convective dryer and 8.14 and 28.85 for the infrared dryer. A kinetic study indicated that dried samples by the infrared dryer could rapidly reach equilibrium moisture content due to exposure to IR radiation. Consequently, the results indicated that the infrared dryer has better performance than the convective dryer regarding drying time, energy consumption, and amount of calcium and antioxidant.