Phosphorylation at serine 482 affects stability of NF90 and its functional role in mitosis.
NF90 is a multifunctional double-strand RNA binding protein with documented roles in transcription, mRNA stability, translation, RNA processing and transport, and mitosis. It is a phosphoprotein that interacts with, and is a substrate for, several protein kinases. The study described here was initiated to gain better understanding of specific NF90 phosphorylation sites and their relationship to mechanisms by which NF90 performs its various functions. Phosphoproteomic studies have identified NF90 serine 482 (S482) as a major phosphorylation site in vivo. Site-specific mutations were introduced at this site and the mutated proteins were expressed in MCF7 cells by transfection. Western blotting was used to examine NF90 expression, stability, and responsiveness to protein kinase activators and inhibitors. Flow cytometry was used to examine effects of NF90 mutation on cell cycle progression. Non-phosphorylatable mutant S482A was unstable compared to phosphomimetic S482E mutant. NF90-S482A expression was greatly enhanced by inhibiting proteasomal degradation or by activating PKC. Identical treatments had little effect on NF90-S482E. In contrast to WT NF90 or NF90-S482E, cells stably expressing NF90-S482A accumulated in M phase when treated with TPA. Phosphorylation at S482 is important for NF90 stability and in regulating its functional role during mitosis. Based on the sequence surrounding S482, mitotic kinase PLK1 is a strong candidate for the enzyme that phosphorylates NF90 at this site.


Magnetic Field Directed Rare-Earth Separations.
The separation of rare-earth ions from one another is challenging due to their chemical and physical similarities. Nearly all rare-earth separations rely upon small changes in ionic radii to direct speciation or reactivity. Herein, we show that the intrinsic magnetic properties of the rare-earth ions impact the separations of light/heavy and selected heavy/heavy binary mixtures. Using TriNOx3- ([{(2-t BuNO)C6 H4 CH2 }3 N]3- ) rare-earth complexes, we efficiently and selectively crystallized heavy rare earths (Tb-Yb) from a mixture with light rare earths (La and Nd) in the presence of an external Fe14 Nd2 B magnet, concomitant with the introduction of a concentration gradient (decrease in temperature). The optimal separation was observed for an equimolar mixture of La:Dy, which gave an enrichment factor of EFLa:Dy =297±31 for the solid fraction, compared to EFLa:Dy =159±22 in the absence of the field, and achieving a 99.7 % pure Dy sample in one step. These results indicate that the application of a magnetic field can improve performance in a molecular separation system for paramagnetic rare-earth cations.


C-reactive protein can predict dose intensity, time to treatment failure and overall survival in HCC treated with lenvatinib.
Lenvatinib has become a first line treatment for unresectable hepatocellular carcinoma (HCC). However, continued administration is impossible in many patients due to treatment resistance and severe adverse events. This study aimed to identify predicting factors to select patients likely to benefit from lenvatinib treatment. We retrospectively analyzed 53 patients who were treated with lenvatinib for unresectable HCC. They were divided to two groups; low C-reactive protein (CRP) group with pretreatment serum CRP level < 1.0 mg/dL and high CRP group with serum CRP level ≥ 1.0 mg/dl. Overall survival (OS), total amount administered, and period of treatment were compared between the two groups. The high CRP group showed a significantly poorer OS than the low CRP group (0.0% vs 71.5%/ 1year, p < 0.01). Multivariate analyses revealed that high CRP was a significant negative factor for OS (HR: 7.69, 95% confidence interval: 2.43-24.3, p < 0.001), and this result was independent of Child-Pugh score and existing tumor factors. Relative dose intensity at 8 weeks was lower (p = 0.01) and time to treatment failure was shorter (P < 0.001) in the high CRP group. CRP level was associated with OS in HCC patients treated with lenvatinib. CRP could be a useful marker to identify patients most likely to benefit from lenvatinib treatment.


Separation of pineal extracts by gelfiltration. V. Location by paper chromatography of a sheep pineal principle inhibiting hypophyseal gonadotropic activity.
Previously we were able to isolate by simple and mild methods from an aqueous sheep pineal extract an inhibiting principle action on the anterior hypophysis of male rats in vitro. This substance could be located by paper electrophoresis. In the present paper we describe the further purification of this active principle by paper chromatography in two different solvents. In two regions possessing a special fluorescence an inhibiting factor of the gonadotropic activity of the anterior pituitary was found in vitro.


Crystallization and preliminary X-ray diffraction analysis of recombinant pentalenene synthase.
Recombinant pentalenene synthase, a 42.5-kDa sesquiterpene cyclase originally isolated from Streptomyces UC5319 and cloned in Escherichia coli, has been crystallized in space group P6(3) with unit cell dimensions a = b = 183.5 A and c = 56.5 A. Hexagonal prismatic crystals, approximately 0.2 x 0.2 x 0.3 mm, diffract to approximately 2.9 A resolution using monochromatic synchrotron radiation. From the universal (and achiral) building block, farnesyl pyrophosphate, pentalenene synthase catalyzes the formation of four stereocenters in the construction of the three fused five-membered rings of pentalenene; this novel sesquiterpene is a precursor to the pentalenolactone family of antibiotics.


Cardiac stem cell therapy. Registered trials and a pilot study in patients with dilated cardiomyopathy.
In cardiac stem cell therapy, the past decade has been interesting with respect to preclinical and clinical research. The high diversity of applied stem cell populations and evaluation methods represent a challenge to fully understand the impact of stem cell administration, leaving uncertain answers to the questions that have been dealt with thus far. In the present work, registered studies in cardiac stem cell therapy are summarized and the study aims are highlighted. Furthermore, preliminary data on the additional intramyocardial administration of CD133+ stem cells in patients undergoing mitral valve surgery are presented.


Bringing Antimicrobial Susceptibility Testing for New Drugs into the Clinical Laboratory: Removing Obstacles in Our Fight against Multidrug-Resistant Pathogens.
There are now several new antibiotics available to treat multidrug-resistant pathogens, and susceptibility testing methods for these drugs are increasingly available at the time of drug approval. However, lack of clarity regarding verification requirements remains a formidable barrier to introducing such testing in clinical laboratories, making these drugs practically unavailable for patient use. We propose a change in the framework for bringing in testing for new antibiotics, focusing on quality control rather than underpowered verification studies.


Association of the Adh Locus with a lethal factor (1(2)stm) in Drosophila melanogaster.
Keeping Drosophila cultures at 28 C results in elimination of all minor multiple ADH bands, thought to be due to conformational change. Thus in diploid and triploid adults heterozygous for the AdhF and AdhS alleles, relative staining intensities are found for the three bands which were in conformity with the assumption that both alleles are equally expressed. Among all polymorphic strains derived from natural Central European and Mediterranean populations, the strain +Tub is unique in that its AdhF allele is closely linked to a new recessive lethal factor, named 1(2)Stm. All AdhF 1/AdhF 1 pupae are unable to emerge, and die. The lethal effect is obvious 50 hr earlier by retarded eye, bristle, and body wall pigmentation. Although all pupae of the phenotype F die, AdhF allele freqnency scarcely seems to be lowered in this natural population.


Risk factors for peritonitis in pediatric peritoneal dialysis: a single-center study.
Recent US registry data and a European multicenter study described increased risk of peritonitis in young children on peritoneal dialysis (PD). No underlying age-specific risk factors could be defined in these reports. Therefore, we analyzed risk factors for peritonitis in children treated by PD as primary renal replacement therapy at the Kinderdialyse, Vienna, and particularly searched for age-specific aspects. Thirty children (15 boys, mean age 4.6 years) received PD [21 automated peritoneal dialysis (APD), nine continuous ambulatory peritoneal dialysis (CAPD)] for 13 months (3-49 months). During the total observation period of 395 dialysis months, 27 peritonitis episodes were diagnosed (1:14.6 months or 0.82/patient per year). Of our population, 43% remained peritonitis free; seven patients suffered from more than one peritonitis episode. Ten potential risk factors [age, gender, PD modality, duration of PD, exit-site status, urine volume, residual glomerular filtration rate (GFR), Kt/V, normalized protein catabolic rate (nPCR), albumin] and four indices of peritonitis outcome (peritonitis incidence, peritonitis burden, risk of suffering more than one episode of peritonitis and chance of staying free from peritonitis) were analyzed. Our study identified six risk factors in univariate analysis, namely age, APD treatment, exit-site infections, low urinary volume, low residual GFR and low nPCR, which were significantly correlated with two or more of the outcome indices. Multivariate analysis identified exit-site infection and residual urine volume as strong independent predictors. In summary, our study identified several age-dependent and age-independent risk factors for peritonitis in pediatric PD. These data demonstrate that the risk for peritonitis in small children is not pre-determined but might be open to therapeutic interventions, such as optimizing exit-site care, dialysis prescription and nutrition management.


Effects of Chinese medicine herbal residues on antibiotic resistance genes and the bacterial community in chicken manure composting.
The use of livestock manure is an important way for antibiotic resistance genes (ARGs) to enter the environment, and composting is an effective method for removing ARGs from livestock manure. In this study, different volume ratios of Chinese medicinal herbal residues (CMHRs) were added to laboratory-scale chicken manure composting to evaluate their effects, if any, on the behavior of ARGs, mobile genetic elements (MGEs), and the bacterial community. At the end of the composting period, the composition of the microbial community changed. Firmicutes decreased and Bacteroidetes increased. The most striking effect was that the relative abundance of the 21 ARGs and 5 MGEs detected decreased by varying degrees in the different treatments (except for sulI and intI1). The removal rate of the ARGs increased with the increased addition of CMHRs. The correlations between transferase genes (tnpA and tnpA-02) and ARGs were significant (p < 0.05); therefore, transposons play an important role in the horizontal gene transfer of ARGs in chicken manure. The results imply that CMHRs would be an effective bulking agent for the removal of ARGs from chicken manure composting.


A novel perfusion imaging technique of the pancreas: contrast-enhanced harmonic EUS (with video).
Contrast-enhanced harmonic-imaging techniques have been unavailable for EUS because of the limited frequency bandwidth and acoustic power output of current echoendoscopes. To investigate the contrast harmonic imaging technique by using a prototype echoendoscope equipped with an adequate broad-band transducer that can detect harmonic signals from the US contrast agents. Identification of optimal settings (study I) and preliminary clinical investigations (study II). Bethesda General Hospital Bergedorf. A total of 104 patients undergoing standard EUS examinations. Contrast-enhanced harmonic EUS (CEH-EUS) was performed by using a prototype echoendoscope and extended pure harmonic detection mode, a specific mode for contrast harmonic imaging. In study I, time-intensity curves for peak signal intensity were calculated after infusion of a contrast agent, SonoVue, and the changes in echo intensity were compared for different mechanical indices and interval times. In study II, intermittent and real-time continuous images of pancreatobiliary and gastroduodenal diseases obtained by CEH-EUS were evaluated in comparison with contrast-enhanced power-Doppler EUS (CED-EUS). In study I, with the optimal mechanical index (0.4), homogeneous parenchymal perfusion images of the pancreas were obtained by intermittent imaging, and finely branching vessels of the pancreas were obtained with real-time continuous imaging. In study II, apparent perfusion and vessel images were observed in pancreatobiliary carcinomas, GI stromal tumors, and lymph-node metastases. CED-EUS failed to depict images of the fine vessels and parenchymal perfusion. The subjective nature of the findings, with a limited number of patients. CEH-EUS successfully visualized parenchymal perfusion and microvasculature in the pancreas and may play an important role in the differential diagnosis of digestive diseases.


More hippocampal neurons in adult mice living in an enriched environment.
Neurogenesis occurs in the dentate gyrus of the hippocampus throughout the life of a rodent, but the function of these new neurons and the mechanisms that regulate their birth are unknown. Here we show that significantly more new neurons exist in the dentate gyrus of mice exposed to an enriched environment compared with littermates housed in standard cages. We also show, using unbiased stereology, that the enriched mice have a larger hippocampal granule cell layer and 15 per cent more granule cell neurons in the dentate gyrus.


Mpwapwa cattle: an Indo-Euro-African synthesis.
Mpwapwa cattle are a synthetic dual-purpose breed developed in the Livestock Production Research Institute at Mpwapwa in Tanzania. The breed has received about 60% of its inheritance from improved dairy breeds originating in the Indian subcontinent (Red Sindhi and Sahiwal), about 30% from African zebu breeds (Boran and Tanzania Shorthorn zebu) and the remaining 10% from European breeds (mainly Ayrshire). The breed comprises only about 1,000 animals in two major herds and is threatened by extinction. The following production parameters have been reported for the herd at the Livestock Production Research Institute, Mpwapwa: age at first calving 45.4 months; calving interval 447 days; lactation milk yield (short lactations deleted) 1,447 to 1,628 kg; daily gain 259 g; carcass weight of steers (four years) 229 kg.


Phenotypic and microarray gene expression analysis of tri-dimensional raft-modeled human head and neck squamous cell carcinoma.
To describe the phenotypic and gene expression differences in monolayer and tri-dimensional cultures systems. Normal oral epithelial cells (NOEC), primary head and neck squamous cell carcinoma (HNSCC), and HNSCC cell lines were used to create and study modeled tri-dimensional tissue. Using cDNA microarray analysis, monolayer and raft-modeled tri-dimensional HNSCC cell lines were compared. NOEC, HNSCC, and both together can be modeled with tri-dimensional differentiation and cytokeratin characteristics analogous to in vivo tissue. Modeling of primary HNSCC resulted in a morphology of invasive HNSCC with areas of direct collagen invasion and MMP2 expression. Gene array analysis suggests that the individual cell lines themselves are the primary gene expression predictor and not the presence of tri-dimensional tissue architecture. This tissue culture modeling system approximates the differentiation and tri-dimensional structure of in vivo tissues, and that raft modeled tri-dimensional HNSCC does not have a significantly different gene expression profile than the corresponding monolayer culture.


C5b-9-activated, K(v)1.3 channels mediate oligodendrocyte cell cycle activation and dedifferentiation.
Voltage-gated potassium (K(v)) channels play an important role in the regulation of growth factor-induced cell proliferation. We have previously shown that cell cycle activation is induced in oligodendrocytes (OLGs) by complement C5b-9, but the role of K(v) channels in these cells had not been investigated. Differentiated OLGs were found to express K(v)1.4 channels, but little K(v)1.3. Exposure of OLGs to C5b-9 modulated K(v)1.3 functional channels and increased protein expression, whereas C5b6 had no effect. Pretreatment with the recombinant scorpion toxin rOsK-1, a highly selective K(v)1.3 inhibitor, blocked the expression of K(v)1.3 induced by C5b-9. rOsK-1 inhibited Akt phosphorylation and activation by C5b-9 but had no effect on ERK1 activation. These data strongly suggest a role for K(v)1.3 in controlling the Akt activation induced by C5b-9. Since Akt plays a major role in C5b-9-induced cell cycle activation, we also investigated the effect of inhibiting K(v)1.3 channels on DNA synthesis. rOsK-1 significantly inhibited the DNA synthesis induced by C5b-9 in OLG, indicating that K(v)1.3 plays an important role in the C5b-9-induced cell cycle. In addition, C5b-9-mediated myelin basic protein and proteolipid protein mRNA decay was completely abrogated by inhibition of K(v)1.3 expression. In the brains of multiple sclerosis patients, C5b-9 co-localized with NG2(+) OLG progenitor cells that expressed K(v)1.3 channels. Taken together, these data suggest that K(v)1.3 channels play an important role in controlling C5b-9-induced cell cycle activation and OLG dedifferentiation, both in vitro and in vivo.


Quantifying the Coupled Kinetic Reactions of Metals/Metalloids on Iron and Manganese Oxides.
Quantifying the coupled kinetic reactions of metals/metalloids on iron and manganese oxides is essential for predicting the fate of contaminants in the environment. In this perspective, a few key issues related to developing the quantitative models for the coupled kinetic reactions of metal and metalloids are discussed, including adsorption/desorption processes, redox reactions, and mineral dissolution/transformation. Future research areas are also briefly discussed.


Improvement of water quality for mass anopheline rearing: evaluation of the impact of ammonia-capturing zeolite on larval development and adult phenotypic quality.
Malaria vector control approaches that rely on mosquito releases such as the sterile insect technique (SIT) and suppression or replacement strategies relying on genetically modified mosquitoes (GMM) depend on effective mass production of Anopheles mosquitoes. Anophelines typically require relatively clean larval rearing water, and water management techniques that minimise toxic ammonia are key to achieving optimal rearing conditions in small and large rearing facilities. Zeolites are extensively used in closed-system fish aquaculture to improve water quality and reduce water consumption, thanks to their selective adsorption of ammonia and toxic heavy metals. The many advantages of zeolites include low cost, abundance in many parts of the world and environmental friendliness. However, so far, their potential benefit for mosquito rearing has not been evaluated. This study evaluated the independent effects of zeolite and daily water changes (to simulate a continuous flow system) on the rearing of An. coluzzii under two feed regimes (powder and slurry feed) and larval densities (200 and 400 larvae per tray). The duration of larval development, adult emergence success and phenotypic quality (body size) were recorded to assess the impact of water treatments on mosquito numbers, phenotypic quality and identification of optimal feeding regimes and larval density for the use of zeolite. Overall, mosquito emergence, duration of development and adult phenotypic quality were significantly better in treatments with daily water changes. In treatments without daily water changes, zeolite significantly improved water quality at the lower larval rearing density, resulting in higher mosquito emergence and shorter development time. At the lower larval rearing density, the adult phenotypic quality did not significantly differ between zeolite treatment without water changes and those with daily changes. These results suggest that treating rearing water with zeolite can improve mosquito production in smaller facilities. Zeolite could also offer cost-effective and environmentally friendly solutions for water recycling management systems in larger production facilities. Further studies are needed to optimise and assess the costs and benefits of such applications to Anopheles gambiae (s.l.) mosquito-rearing programmes.


Insulin, glucagon, and leptin in critically ill foals.
Endocrine dysregulation of hormones of energy metabolism is well documented in critically ill humans, but limited information exists in septic foals. The purpose of this study was to provide information on the hormonal response to energy metabolism in critically ill foals, focusing on insulin, glucagon, and leptin. Concentrations of insulin, glucagon, leptin, and triglycerides will be higher, whereas glucose concentration will be lower in septic foals than in healthy and sick nonseptic foals. The magnitude of these differences will be associated with severity of disease and nonsurvival. Forty-four septic, 62 sick nonseptic, and 19 healthy foals <7 days of age. In this prospective multicenter cross-sectional study, blood samples were collected at admission. Foals with positive blood culture or sepsis score ≥12 were considered septic. Septic foals had lower glucose and insulin and higher triglyceride and glucagon concentrations than did healthy foals. Glucagon concentrations were not different between septic foals that died (n = 14) or survived (n = 30). Higher insulin and lower leptin concentrations were associated with mortality. Quantitative insulin-sensitivity check index was higher in septic foals. Energy metabolism and the endocrine response of related hormones in septic foals are characterized by hypoglycemia, hypertriglyceridemia, low insulin concentration, and high glucagon concentration. Leptin and insulin may have prognostic value for nonsurvival in septic foals. The hormonal response related to energy metabolism in critical illness differs between foals and humans.


Advances in salmonid fish immunology: A review of methods and techniques for lymphoid tissue and peripheral blood leucocyte isolation and application.
Evaluating studies over the past almost 40 years, this review outlines the current knowledge and research gaps in the use of isolated leucocytes in salmonid immunology understanding. This contribution focuses on the techniques used to isolate salmonid immune cells and popular immunological assays. The paper also analyses the use of leucocytes to demonstrate immunomodulation following dietary manipulation, exposure to physical and chemical stressors, effects of pathogens and parasites, vaccine design and application strategies assessment. We also present findings on development of fish immune cell lines and their potential uses in aquaculture immunology. The review recovered 114 studies, where discontinuous density gradient centrifugation (DDGC) with Percoll density gradient was the most popular leucocyte isolation method. Fish head kidney (HK) and peripheral blood (PB) were the main sources of leucocytes, from rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar). Phagocytosis and respiratory burst were the most popular immunological assays. Studies used isolated leucocytes to demonstrate that dietary manipulations enhance fish immunity, while chemical and physical stressors suppress immunity. In addition, parasites, and microbial pathogens depress fish innate immunity and induce pro-inflammatory cytokine gene transcripts production, while vaccines enhance immunity. This review found 10 developed salmonid cell lines, mainly from S. salar and O. mykiss HK tissue, which require fish euthanisation to isolate. In the face of high costs involved with density gradient reagents, the application of hypotonic lysis in conjunction with mico-volume blood methods can potentially reduce research costs, time, and using nonlethal and ethically flexible approaches. Since the targeted literature review for this study retrieved no metabolomics study of leucocytes, indicates that this approach, together with traditional technics and novel flow cytometry could help open new opportunities for in vitro studies in aquaculture immunology and vaccinology.


Mechanism based QSAR studies of N-phenylbenzamides as antimicrobial agents.
N-Phenyl benzamides are potent antibacterial agents. They are active against both Gram-positive and Gram-negative bacteria. The Gram-positive bacteria have strong and thick cell wall while the Gram-negative bacterial have thin and permeable cell wall. The DFT based QSAR reveals that molecular weight and total energy significantly contribute to activity against both kinds of target. The electrophilicity index involved in QSAR models derived with anti-Gram-positive activity indicates the dominance of electrostatic interaction. The molar refractivity and logP is involved in QSAR model derived with anti-Gram-negative activity shows steric and hydrophobic interaction. The CoMFA and CoMSIA results also indicate that anti-Gram-positive bacterial activity is a function of electrostatic field effect but the anti-Gram-negative activity depends on hydrophobicity and steric field effect. The CoMFA and CoMSIA contour maps give an indication, the electropositive group around benzene "X" and an electronegative group around carbonyl oxygen is desirable for better anti-Gram-positive bacterial activity. A hydrophobic group around meta position of ring "X" with bulky group at ortho position and a small group at para position are desirable for better activity against Gram-negative target. The findings are reasonable and the mechanism might be different due to difference in composition of cell wall. The cell wall of Gram-positive target does not allow the permeability and only external electrostatic interaction is possible while the cell wall of Gram-negative target allows the permeability of molecules inside the cell for possible hydrophobic and steric bulk interaction.


Melatonin: Potential avenue for treating iron overload disorders.
Iron overload as a highly risk factor, can be found in almost all human chronic and common diseases. Iron chelators are often used to treat iron overload; however, patient adherence to these chelators is poor due to obvious side effects and other disadvantages. Numerous studies have shown that melatonin has a high iron chelation ability and direct free radical scavenging activity, and can inhibit the lipid peroxidation process caused by iron overload. Therefore, melatonin may become potential complementary therapy for iron overload-related disorders due to its iron chelating and antioxidant activities. Here, the research progress of iron overload is reviewed and the therapeutic potential of melatonin in the treatment of iron overload is analyzed. In addition, studies related to the protective effects of melatonin on oxidative damage induced by iron overload are discussed. This review provides a foundation for preventing and treating iron homeostasis disorders with melatonin.


Rapid deployment of inexpensive open-source orbital shakers in support of high-throughput screening.
Open-source projects continue to grow in popularity alongside open-source educational resources, software, and hardware tools. The impact of this increased availability of open-source technologies is that end users are empowered to have greater control over the tools that they work with. This trend extends in the life science laboratory space, where new open-source projects are routinely being published that allow users to build and modify scientific equipment specifically tailored to their needs, often at a reduced cost from equivalent commercial offerings. Recently, we identified a need for a compact orbital shaker that would be usable in temperature and humidity-controlled incubators to support the development and execution of a high-throughput suspension cell-based assay. Based on the requirements provided by staff biologists, an open-source project known as the DIYbio orbital shaker was identified on Thingiverse, then quickly prototyped and tested. The initial orbital shaker prototype based on the DIYbio design underwent an iterative prototyping and design process that proved to be straightforward due to the open-source nature of the project. The result of these efforts has been the successful initial deployment of ten shakers as of August 2021. This afforded us the scalability and efficacy needed to complete a large-scale screening campaign in less time and at less cost than if we purchased larger, less adaptable orbital shakers. Lessons learned from prototyping, modifying, validating, deploying and maintaining laboratory devices based on an open-source design in support of a full-scale drug discovery high-throughput screening effort are described within this manuscript.


Use of random matrix theory in the discovery of resting state brain networks.
Connectomics identifies brain networks in vivo in resting state functional MRI. However, the presence of noise produces spurious identification of brain networks, which have low test-retest reliability. A Network Based Statistics approach to network identification has been previously proposed that affords much better statistical power relative to Bonferroni method but nevertheless provides a sufficiently conservative, family-wise control for false positives. We propose the use of Random Matrix Theory (RMT) to discover brain networks and to associate those networks with demographic and clinical variables. We parcellated the brain into cortical and subcortical regions using either an anatomical or a functional brain atlas. We applied RMT to study functional connectivity across brain regions by first computing the correlation matrix for time courses in those brain regions and then identifying eigenvalues that deviate from the theoretical random distribution that RMT predicts, on the assumption that real brain networks would produce eigenvalues that differ significantly from the random distribution. We assessed the specificity and test-retest reliability of identified networks through application of this RMT-based approach to (1) synthetic data generated under the null-hypothesis, (2) resting state functional MRI data from 4 real-world cohorts of patients and healthy controls, and (3) synthetic data generated by the addition of increasing amounts of noise to real-world datasets. Our findings showed that RMT method was robust to the atlas used for parcellating the brain and did not discover a brain network in synthetic data when in fact a network was not present (i.e., specificity was high); RMT-identified networks in the real-world dataset had high test-retest reliability; and RMT-based method consistently discovered the same network in the presence of increasing noise in the real-world dataset.


Cerebral Cryptococcomas: A Systematic Scoping Review of Available Evidence to Facilitate Diagnosis and Treatment.
Recommendations for managing patients with cerebral cryptococcomas are scarce across multiple clinical guidelines. Due to the deficiency of high-quality data coupled with an increasing number of at-risk patients, the purpose of this review is to describe the demographic characteristics, causative pathogen, intracranial imaging, surgical and/or pharmacological interventions, as well as outcomes of patients with cerebral cryptococcomas to improve recognition and management. We conducted a scoping review in accordance with the PRISMA guidelines using PubMed and Web of Science. Reports were included if the following details were presented: (1) site of infection; (2) treatment details which at least include the specific antifungal therapy administered, if applicable; and (3) patient outcome. A total of 40 records representing 47 individual patients were included, of which the median age was 48.5 years, 75% were male, and 60% reported a significant past medical, surgical, or social history. C. neoformans was isolated more often than C. gattii (74% vs. 26%, respectively). Patients most often presented with headache, altered mental status and/or confusion, and vomiting occurring over a median of 30 days; though few were noted to have significant findings on physical examination. More than 50% of patients had a single cerebral cryptococcoma lesion, whereas perilesional edema was present in 73% of cases. Surgical intervention occurred in 49% of patients. An amphotericin B-based formulation was administered as "induction" therapy to 91% of patients, but combined with flucytosine or fluconazole in only 58%, for an overall median of 42 days. Fifty two percent of patients received "maintenance" therapy for a median of 126 days, in which fluconazole was most often used. Corticosteroids were administered to approximately 30% of patients for a median of 31.5 days. Overall, mortality was 34%. Based on our findings, management should include antifungal therapy for a minimum of 6 months with considerations for concomitant corticosteroids in the setting of perilesional edema, as well as surgical intervention. Emphasis should be placed on providing well-documented treatment details in future case reports and series to allow for the development of more concise evidence-based recommendations.


No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol O-methyltransferase activity.
Catechol O-methyltransferase (COMT) inactivates catecholamines by methylating their m-hydroxy group. Some previous studies using biochemical methods have found higher levels of COMT activity in schizophrenic patients. Recently, the genetic polymorphism that underlies variation in COMT activity, which results in the creation of a NlaIII restriction site in the low-activity allele, has been elucidated. This study investigated this polymorphism in 78 unrelated schizophrenic patients and 78 comparison subjects matched for age and ethnicity. High-molecular-weight DNA was isolated from lymphocytes with routine procedures, and each individual was typed for high and low COMT activity. The frequency of the NlaIII polymorphism was 0.51 in the schizophrenic patients and 0.53 in the comparison subjects, and no significant allelic or genotypic associations were observed. There was no evidence for variation in COMT activity between a group of schizophrenic patients and matched comparison subjects.


Functional advantage after radical segmentectomy versus lobectomy for lung cancer.
Although several reports have recently demonstrated that segmentectomy for small-sized N0 lung cancer leads to recurrence and survival rates equivalent to those associated with lobectomy, controversy regarding the postoperative functional advantage in the former over the latter still persists. The purpose of this study was to evaluate the degree of postoperative functional loss in patients undergoing segmentectomy or lobectomy for lung cancer. We analyzed patients able to tolerate lobectomy, who underwent radical segmentectomy (n = 38) or lobectomy (n = 45) for non-small-cell lung cancer. Functional testing included forced vital capacity, forced expiratory volume in 1 second, and anaerobic threshold measured preoperatively and at 2 and 6 months after surgery. Preoperative function tests showed no differences between segmentectomy and lobectomy patients. A positive and significant correlation was found between the number of resected segments versus loss of forced vital capacity (r = 0.518, p < 0.0001 at 2 months; r = 0.604, p < 0.0001 at 6 months) and loss of forced expiratory volume in 1 second (r = 0.492, p < 0.0001 at 2 months; r = 0.512, p < 0.0001 at 6 months). The postoperative reduction of forced vital capacity (p = 0.0006) and forced expiratory volume in 1 second (p = 0.0007) was significantly less in the segmentectomy group; however, a marginally significant benefit was observed in this group for anaerobic threshold (p = 0.0616). The extent of removed lung parenchyma directly affected that of postoperative functional loss even at 6 months after surgery, and segmentectomy offered significantly better functional preservation compared with lobectomy. These results indicate the importance of segmentectomy for early staged lung cancer.


Antimicrobial-Resistant Infections after Turkey/Syria Earthquakes, 2023.
Increased rates of multidrug-resistant microbes have been reported after earthquakes. After the 2023 earthquakes in Turkey and Syria, the number of associated highly drug-resistant pathogens and nosocomial transmission will probably surge in hospitals treating injured patients. It is not too late to act to prevent antimicrobial-resistant infections from compounding these tragedies.


Clinical ACO phenotypes: Description of a heterogeneous entity.
Because ACO (Asthma-COPD-Overlap) does not fill out asthma or COPD (Chronic Obstructive Pulmonary Disease) criteria, such patients are poorly evaluated. The aim of this study was to screen asthma and COPD for an alternative diagnosis of ACO, then to determine subgroups of patients, using cluster analysis. Using GINA-GOLD stepwise approach, asthmatics and COPD were screened for ACO. Clusterization was then performed employing Multiple Correspondent Analysis (MCA) model, encompassing 9 variables (age, symptoms onset, sex, BMI (Body Mass Index), smoking, FEV-1, dyspnea, exacerbation, comorbidity). Finally, clusters were compared to determine phenotypes. MCA analysis was performed on 172 ACO subjects. To better distinguish clusters, the analysis was then focused on 55 subjects, having at least one cosine squared >0.3. Six clusters were identified, allowing the description of 4 phenotypes. Phenotype A represented overweighed heavy smokers, with an early onset and a severe disease (27% of ACO patients). Phenotype B gathered similar patients, with a late onset (29%). Patients from Phenotypes C-D were slighter smokers, presenting a moderate disease, with early and late onset respectively (respectively 13% and 31%). By providing evidences for clusters within ACO, our study confirms its heterogeneity, allowing the identification of 4 phenotypes. Further prospective studies are mandatory to confirm these data, to determine both specific management requirements and prognostic value.


The renal response to electrical stimulation of renal efferent sympathetic nerves in the anaesthetized greyhound.
1. The effect of direct electrical stimulation of the renal efferent nerves upon renal haemodynamics and function was studied in greyhounds anaesthetized with chloralose and artificially ventilated. The left kidney was neurally and vascularly isolated, and perfused with blood from one of the femoral arteries at a constant pressure of 99 +/- 1 mmHg. Renal blood flow was measured with a cannulating electromagnetic flow probe placed in the perfusion circuit, glomerular filtration rate by creatinine clearance, urinary sodium excretion by flame photometry and solute excretion by osmometry. Beta-Adrenergic receptor activation was blocked by the infusion of dl-propranolol (17 micrograms kg-1 min-1). The peripheral ends of the ligated renal nerves were stimulated at 0.5, 1.0, 1.5 and 2.0 Hz. 2. At 0.5 Hz frequency only osmolar excretion was significantly reduced (10.3 +/- 3.2%, P less than 0.05, n = 6). Reductions in sodium excretion (53.6 +/- 8.5%, P less than 0.01, n = 6) and water excretion (26.9 +/- 8.0%, P less than 0.05, n = 6) and further reductions of osmolar excretion (20.7 +/- 3.7%, P less than 0.01, n = 6) were observed at 1.0 Hz; however, these were observed in the absence of significant changes in renal blood flow and glomerular filtration rate. Significant reductions were observed in glomerular filtration rate at 1.5 Hz (16.3 +/- 4.1%, P less than 0.02, n = 5) and in renal blood flow at 2.0 Hz (13.1 +/- 4.0%, P less than 0.05, n = 5). Further reductions in urine flow and sodium excretion were also observed at these higher frequencies. 3. These results clearly show that significant changes in renal tubular function can occur in the absence of changes in renal blood flow and glomerular filtration rate when the renal nerves are stimulated electrically from a zero baseline activity up to a frequency of 1.5 Hz. Higher frequencies caused significant changes in both renal haemodynamics and function.


Senescence and functional failure in hematopoietic stem cells.
Maintaining normal function of hematopoietic stem cells (HSCs) is critical to blood coagulation, oxygen transportation, and host defense against infection. A potential cause of HSC dysfunction is senescence, in which HSCs and progenitor cells suffer from proliferative arrest. Studies on humans and various animal models have indicated that HSCs can become senescent, showing a significant decline in functional ability with increasing age. There are genetic elements mapped to specific chromosomal sites that regulate HSC senescence. These elements may differ among species, strains, and even individuals. HSC senescence and related pathological effects may not be obvious during normal lifetime under most circumstances since individual primitive HSC clones can function long-term to produce progeny that sustain life-long mature blood cell production. Shortening of telomeres at the chromosomal ends could contribute to HSC senescence, especially when HSCs are stressed under certain pathological conditions. Future studies should define the molecular elements that are important in the regulation of HSC senescence.


Computerised biofeedback achieving continence in high anal atresia.
Computerised biofeedback has been used to attempt to improve continence in three boys with high anal atresia. The results obtained so far have been extremely encouraging. Over a period of six months progressive improvement has taken place and been maintained in each child.


"Reversed" intraguild predation: red fox cubs killed by pine marten.
Camera traps deployed at a badger Meles meles set in mixed pine forest in north-eastern Poland recorded interspecific killing of red fox Vulpes vulpes cubs by pine marten Martes martes. The vixen and her cubs settled in the set at the beginning of May 2013, and it was abandoned by the badgers shortly afterwards. Five fox cubs were recorded playing in front of the den each night. Ten days after the first recording of the foxes, a pine marten was filmed at the set; it arrived in the morning, made a reconnaissance and returned at night when the vixen was away from the set. The pine marten entered the den several times and killed at least two fox cubs. It was active at the set for about 2 h. This observation proves that red foxes are not completely safe from predation by smaller carnivores, even those considered to be subordinate species in interspecific competition.


Aldosterone and the kidney: rapid regulation of renal microcirculation.
Recent studies provide evidence that aldosterone (Aldo) accelerates hypertension, proteinuria and glomerulosclerosis in animal models of chronic renal failure. Although the underlying mechanisms are not well defined, Aldo may exert these deleterious renal effects by elevating renal vascular resistance (RVR) and glomerular capillary pressure (P(GC)). To test this possibility, we studied the action of Aldo on rabbit afferent (Af-) and efferent arterioles (Ef-Arts), crucial vascular segments to the control of glomerular hemodynamics. Aldo caused rapid (within 5 min) constriction in both arterioles. The constriction was not affected by spironolactone but was reproduced by membrane-impermeable albumin-conjugated Aldo, suggesting that vasoconstrictor actions are non-genomic. This notion was further supported by the finding that neither actinomycin D nor cycloheximide had effect. The vasoconstrictor action of Aldo on Af-Arts was inhibited by nifedipine (L-type calcium channel blocker), whereas that on Ef-Arts was inhibited by efonidipine (both L- and T-type calcium channel blocker) but not nifedipine. Disrupting the endothelium or nitric oxide (NO) synthesis inhibition augmented the vasoconstriction in Af-Arts, demonstrating that endothelium-derived NO modulates the vasoconstrictor actions of Aldo. Thus, Aldo causes non-genomic vasoconstriction via calcium mobilization thorough L- or T-type calcium channels in Af- or Ef-Arts, respectively. These vasoconstrictor actions on the glomerular microcirculation may play an important role in the pathophysiology and progression of renal diseases by elevating RVR and P(GC), especially when endothelium functions are impaired. In addition to our study, this review describes recent findings on the rapid cardiovascular actions of Aldo, with a particular attention to the renal hemodynamics.


Longitudinal Changes in Overall 3D Supraspinatus Muscle Volume and Intramuscular Fatty Infiltration After Arthroscopic Rotator Cuff Repair.
There is considerable debate regarding the longitudinal changes in overall rotator cuff (RC) muscle atrophy and intramuscular fatty infiltration (FI) following RC repair. We analyzed the longitudinal changes in overall 3D supraspinatus muscle volume and intramuscular FI (3D FI) to determine the effect of tear size and repair integrity on 3D muscle volume and intramuscular FI. Forty-seven patients who underwent arthroscopic RC repair and had 6-point Dixon shoulder magnetic resonance imaging (MRI) preoperatively and 3 and 12 months postoperatively were enrolled. The 3D supraspinatus muscle volume and intramuscular FI were calculated at the 3 time points, and their changes over time were evaluated in the entire cohort as well as according to tear size and repair integrity. The agreement of the difference between time points among the patients was assessed by Bland-Altman analysis. In the cohort as a whole, there were no significant longitudinal changes in the 3D supraspinatus volume (19.65 ± 7.26 to 19.48 ± 7.46 cm3, p = 0.911) or 3D FI (17.18% ± 8.85% to 17.30% ± 9.18%, p = 0.977) from preoperatively to the final 12-month time point, overall and in the tear size and repair integrity subgroups. The 3D supraspinatus volume was significantly decreased at 3 months (17.39 ± 6.12 cm3, p < 0.001) but then increased again by 12 months (p < 0.001), reaching a value similar to the preoperative level. The 3D FI had a small increase at 3 months (18.18% ± 9.65%, p = 0.097) but subsequently decreased slightly again (p = 0.211), such that there were no significant longitudinal changes. The differences in the 3D supraspinatus volume and FI between these time points showed high agreement among patients. The overall 3D supraspinatus volume and 3D FI showed no longitudinal change between the preoperative baseline and the 12-month follow-up after arthroscopic RC repair. Tear size and repair integrity had no impact on the longitudinal patterns of muscle volume and intramuscular FI changes. The 3D supraspinatus volume decreased during the first 3 months but recovered to baseline at 12 months postoperatively; 3D FI was relatively stable throughout the 12 months of follow-up after repair. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


Why does the immune system destroy pancreatic β-cells but not α-cells in type 1 diabetes?
A perplexing feature of type 1 diabetes (T1D) is that the immune system destroys pancreatic β-cells but not neighbouring α-cells, even though both β-cells and α-cells are dysfunctional. Dysfunction, however, progresses to death only for β-cells. Recent findings indicate important differences between these two cell types. First, expression of BCL2L1, a key antiapoptotic gene, is higher in α-cells than in β-cells. Second, endoplasmic reticulum (ER) stress-related genes are differentially expressed, with higher expression levels of pro-apoptotic CHOP in β-cells than in α-cells and higher expression levels of HSPA5 (which encodes the protective chaperone BiP) in α-cells than in β-cells. Third, expression of viral recognition and innate immune response genes is higher in α-cells than in β-cells, contributing to the enhanced resistance of α-cells to coxsackievirus infection. Fourth, expression of the immune-inhibitory HLA-E molecule is higher in α-cells than in β-cells. Of note, α-cells are less immunogenic than β-cells, and the CD8+ T cells invading the islets in T1D are reactive to pre-proinsulin but not to glucagon. We suggest that this finding is a result of the enhanced capacity of the α-cell to endure viral infections and ER stress, which enables them to better survive early stressors that can cause cell death and consequently amplify antigen presentation to the immune system. Moreover, the processing of the pre-proglucagon precursor in enteroendocrine cells might favour immune tolerance towards this potential self-antigen compared to pre-proinsulin.


Effect of thermal and mechanical load cycling on nanoleakage of Class II restorations.
To evaluate the effect of thermal and mechanical cycling on the degree and pattern of nanoleakage on cervical margins of Class II restorations. Forty box-type Class II cavities were prepared on bovine incisors. The cavities were restored with Single Bond and Z-250 composite resin (3M-ESPE) according to manufacturer's instructions. The teeth were randomly assigned to 4 groups: G1, control; G2, thermal cycling (2000 cycles, 5 to 55 degrees C); G3, mechanical load cycling (100,000 cycles, 50 N); G4, thermal and mechanical load cycling group (2000 cycles 5 to 5 degrees C/100,000 cycles, 50 N). The specimens were then sealed leaving a 1 mm window around the cervical margin interface. Samples were immersed in a 50% w/v ammoniacal silver nitrate solution for 24 h, and exposed to a photodeveloping solution for 8 h. Specimens were sectioned longitudinally, embedded in epoxy resin, polished and mounted on stubs, gold sputter coated, and examined under SEM using backscattered electron mode. Silver particle penetration length was measured directly on the SEM monitor and calculated as the percentage of the total length of cut dentin surface that was penetrated by silver nitrate. The data were analyzed with ANOVA and Fisher's PLSD test (p < 0.05). The degree of nanoleakage significantly increased when thermal and mechanical cycling was performed on the same specimens, as compared to the other groups (p < 0.05). No differences were observed between the control, thermal cycling, and mechanical cycling groups. No difference in nanoleakage pattern was observed between the groups. Thermal and mechanical cycling combined adversely affected nanoleakage values. Simulation of the oral condition might be crucial to better evaluate and understand the performance of adhesive materials.


Role of transmitral blood flow velocity by Doppler echocardiography in the evaluation of coronary artery disease.
To determine the relation between presence and severity of coronary artery disease and diastolic filling abnormalities by Doppler echocardiography, recordings of transmitral inflow velocity were made at rest in 90 patients with coronary artery disease and 28 normals. At the time of the Doppler examination, 81 patients with coronary artery disease (90%) and 10 normals (36%) were treated with antianginal medications. No difference was found in the ratio between early (E) and late (A) diastolic filling velocity (E/A ratio) when comparing patients with greater than 70% obstruction of at least one coronary artery to age-matched normals, regardless of the presence or absence of wall motion abnormalities. The E/A ratio was 1.3 +/- 0.46 in coronary patients with normal wall motion, 1.2 +/- 0.47 in coronary patients with abnormal wall motion, and 1.3 +/- 0.53 in both samples of age-matched normals. Multivariate analysis of the relation between E/A ratio and other variables showed that heart rate (F = 24.46, p less than 0.00001) and age (F = 19.51, p less than 0.00001) were significant independent determinants of the E/A ratio, while the presence or severity of coronary artery disease, the presence of hypertension, the magnitude of wall motion abnormalities, and end-diastolic dimension by echocardiography were not. These data suggest that transmitral inflow velocity recordings by Doppler have limited value for the recognition of coronary artery disease, since the E/A ratio is profoundly influenced by other factors, such as heart rate and age.


LDL cholesterol target achievement in heterozygous familial hypercholesterolemia patients according to 2019 ESC/EAS lipid guidelines: Implications for newer lipid-lowering treatments.
The 2019 European guidelines (ESC/EAS) for the treatment of dyslipidaemias recommend more aggressive targets for low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). Current lipid-lowering treatment is often inadequate to achieve these targets. Data from the HELLAS-FH registry were analysed to assess achievement of LDL-C targets in adults with FH based on the 2019 ESC/EAS guidelines. In patients who had not achieved LDL-C target, the maximally reduced LDL-C value was calculated after theoretical switch to rosuvastatin/ezetimibe 40/10 mg/day. The percentage of patients who remained candidates for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) was then calculated. Patients (n = 1694, mean age 50.8 ± 14.7 years) had LDL-C levels 242 ± 71 mg/dL (6.3 ± 1.8 mmol/L) at diagnosis. Most treated patients were receiving statins (97.5%) and about half were on additional ezetimibe (47.5%). Based on the 2019 ESC/EAS guidelines the percentage of patients achieving LDL-C goals was only 2.7%. Following theoretical up titration to rosuvastatin/ezetimibe 40/10 mg, LDL-C target achievement rate would increase to 5.9%. In this scenario, most patients (55.9%) would be eligible for PCSK9i treatment. Following theoretical administration of a PCSK9i, LDL-C target achievement rate would rise to 57.6%. However, 42.4% of patients would still be eligible for further LDL-C lowering treatment. Most FH patients do not reach new LDL-C targets even if on maximum intensity statin/ezetimibe treatment. In this case, more than half of FH patients are candidates for PCSK9i therapy and a considerable proportion may still require additional LDL-C lowering.


Retinal neurodegeneration on optical coherence tomography and cerebral atrophy.
Neurodegeneration in dementia is mainly evaluated by assessing cerebral atrophy, while retinal neurodegeneration can be quantified in vivo using optical coherence tomography (OCT). We examined the association of retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thinning with global and regional cerebral atrophy on magnetic resonance imaging (MRI). Malay participants aged 60-80 years from the Epidemiology of Dementia in Singapore Study underwent comprehensive examinations, including 3-Tesla cranial MRI. RNFL and GC-IPL thicknesses were obtained from spectral domain-OCT; and cerebral grey and white matter volumes were obtained from MRI scans using a validated segmentation tool. Linear regression models were constructed with adjustment for age and sex; and additionally for vascular risk factors and MRI markers including intracranial volume. 164 participants without glaucoma with gradable quality MRI and OCT scans were included for analysis. GC-IPL thinning was associated with reduction in total brain volume in the occipital (mean change in GC-IPL per standard deviation (SD) decrease in occipital lobe volume: -1.77 μm, 95% confidence interval (CI) -6.55 to 0.01 μm) and temporal lobes (mean change in GC-IPL per SD decrease in temporal lobe volume: -3.45 μm, 95%CI -5.40 to -1.49 μm) in multivariate adjusted models. In particular, GC-IPL thinning was primarily associated with grey matter volume, whereas no association was found with white matter changes. Retinal neuronal damage, as reflected by GC-IPL thinning, was independently associated with grey matter loss in the occipital and temporal lobes, suggesting that retinal OCT may provide insights for assessing neurodegeneration in the brain.


Therapeutic CPAP Level Predicts Upper Airway Collapsibility in Patients With Obstructive Sleep Apnea.
Upper airway collapsibility is a key determinant of obstructive sleep apnea (OSA) which can influence the efficacy of certain non-continuous positive airway pressure (CPAP) treatments for OSA. However, there is no simple way to measure this variable clinically. The present study aimed to develop a clinically implementable tool to evaluate the collapsibility of a patient's upper airway. Collapsibility, as characterized by the passive pharyngeal critical closing pressure (Pcrit), was measured in 46 patients with OSA. Associations were investigated between Pcrit and data extracted from patient history and routine polysomnography, including CPAP titration. Therapeutic CPAP level, demonstrated the strongest relationship to Pcrit (r2=0.51, p < .001) of all the variables investigated including apnea-hypopnea index, body mass index, sex, and age. Patients with a mildly collapsible upper airway (Pcrit ≤ -2 cmH2O) had a lower therapeutic CPAP level (6.2 ± 0.6 vs. 10.3 ± 0.4 cmH2O, p < .001) compared to patients with more severe collapsibility (Pcrit > -2 cmH2O). A therapeutic CPAP level ≤8.0 cmH2O was sensitive (89%) and specific (84%) for detecting a mildly collapsible upper airway. When applied to the independent validation data set (n = 74), this threshold maintained high specificity (91%) but reduced sensitivity (75%). Our data demonstrate that a patient's therapeutic CPAP requirement shares a strong predictive relationship with their Pcrit and may be used to accurately differentiate OSA patients with mild airway collapsibility from those with moderate-to-severe collapsibility. Although this relationship needs to be confirmed prospectively, our findings may provide clinicians with better understanding of an individual patient's OSA phenotype, which ultimately could assist in determining which patients are most likely to respond to non-CPAP therapies.


Estimated long-term effect of calcitonin treatment in acute osteoporotic spine fractures.
A 12-month prospective controlled study was conducted in 28 patients with acute osteoporotic spine fractures to evaluate and compare the effect of calcitonin treatment and cyclical hormone replacement therapy on forearm bone mineral content (BMC) and bone turnover. We established two treatment groups and a control group of women with postmenopausal osteoporosis (n = 28). Group A (n = 10) received 100 U of calcitonin by subcutaneous self-application on alternate days and oral calcium (Ca) for 6-8 weeks. Group B (n = 10) received cyclical estrogen/gestagen replacement therapy over 12 months and oral calcium. The control group (n = 8) received analgetic treatment and 500 mg Ca daily. BMC was measured by single photon absorptiometry (SPA) with I 125 before and 6 and 12 months after the onset of the therapies. Ca, phosphorus (P), alkaline phosphatase, and 2-hour urinary OH-proline excretion were measured to classify bone turnover. One year after the onset of the two therapies, forearm BMC measured by SPA showed a significant increase in the group under hormone replacement therapy (P less than 0.025) as well as in the calcitonin group (P less than 0.05), although the latter underwent treatment only over a short period (6-8 weeks). In the same period, BMC decreased significantly in the control group (P less than 0.025). These results demonstrate that short-term calcitonin treatment over 6-8 weeks is as effective as long-term hormone replacement therapy, both therapies increasing forearm BMC measured by SPA.


Crystal growth, structural, thermal and mechanical behavior of l-arginine 4-nitrophenolate 4-nitrophenol dihydrate (LAPP) single crystals.
Single crystals of l-arginine 4-nitrophenolate 4-nitrophenol dihydrate (LAPP) have been grown successfully from the solution of l-arginine and 4-nitrophenol. Slow evaporation of solvent technique was adopted to grow the bulk single crystals. Single crystal X-ray diffraction analysis confirms the grown crystal has monoclinic crystal system with space group of P21. Powder X-ray diffraction analysis shows the good crystalline nature. The crystalline perfection of the grown single crystals was analyzed by HRXRD by employing a multicrystal X-ray diffractometer. The functional groups were identified from proton NMR spectroscopic analysis. Linear and nonlinear optical properties were determined by UV-Vis spectrophotometer and Kurtz powder technique respectively. It is found that the grown crystal has no absorption in the green wavelength region and the SHG efficiency was found to be 2.66 times that of the standard KDP. The Thermal stability of the crystal was found by obtaining TG/DTA curve. The mechanical behavior of the grown crystal has been studied by Vicker's microhardness method.


A unique and essential role for insulin in the phenotypic expression of rat mammary epithelial cells unrelated to its function in cell maintenance.
Mammary explants from pregnant rats can be induced in regard to casein synthesis and alpha-lactalbumin activity when cultured in the presence of hydrocortisone, prolactin and levels of insulin approaching physiological concentrations. No detectable induction occurs in the absence of insulin. Although epidermal growth factor and multiplication stimulating activity, in the presence of hydrocortisone, can maintain the initial level of NADH-cytochrome c reductase as well as insulin, neither can substitute effectively for insulin in the induction of the milk proteins. Proinsulin, nerve growth factor, platelet-derived growth factor and fibroblast growth factor are also ineffective substitutes for insulin in this regard. Whereas prolonged tissue exposure to multiplication stimulating activity, hydrocortisone and prolactin does not result in induction of alpha-lactalbumin activity, subsequent addition of insulin leads to prompt response. The results suggest that the ability of insulin to function as a unique, essential factor in the induction of rat milk proteins is independent of its cell-maintenance activity. Thus, in addition to its well established functions in metabolic processes, insulin appears to play a vital role in certain developmental processes.


Manipulating polymer composition to create low-cost, high-fidelity sensors for indoor CO2 monitoring.
Carbon dioxide (CO2) has been linked to many deleterious health effects, and it has also been used as a proxy for building occupancy measurements. These applications have created a need for low-cost and low-power CO2 sensors that can be seamlessly incorporated into existing buildings. We report a resonant mass sensor coated with a solution-processable polymer blend of poly(ethylene oxide) (PEO) and poly(ethyleneimine) (PEI) for the detection of CO2 across multiple use conditions. Controlling the polymer blend composition and nanostructure enabled better transport of the analyte gas into the sensing layer, which allowed for significantly enhanced CO2 sensing relative to the state of the art. Moreover, the hydrophilic nature of PEO resulted in water uptake, which provided for higher sensing sensitivity at elevated humidity conditions. Therefore, this key integration of materials and resonant sensor platform could be a potential solution in the future for CO2 monitoring in smart infrastructure.


Prognostic relevance of sarcopenia, geriatric, and nutritional assessments in older patients with diffuse large B-cell lymphoma: results of a multicentric prospective cohort study.
This prospective study aimed to investigate the prognostic effect of sarcopenia, geriatric, and nutritional status in older patients with diffuse large B-cell lymphoma (DLBCL). Ninety-five patients with DLBCL older than 70 years who were treated with immunochemotherapy were included. The lumbar L3 skeletal muscle index (L3-SMI) was measured by computed tomography at baseline, and sarcopenia was defined as low L3-SMI. Geriatric assessment included G8 score, CIRS-G scale, Timed Up and Go test, and instrumental activity of daily living. Nutritional status was assessed using the Mini Nutritional Assessment and the body mass index, and several scores used in the literature incorporating nutritional and inflammatory biomarkers, namely the Nutritional and inflammatory status (NIS), Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Glasgow Prognostic Score.Fifty-three patients were considered sarcopenic. Sarcopenic patients displayed higher levels of inflammation markers and lower levels of prealbumin than non-sarcopenic patients. Sarcopenia was associated with NIS, but was not associated with severe adverse events and treatment disruptions. They were, however, more frequent among patients with elevated NIS. Sarcopenia did not appear in this study as a prognostic factor for progression-free survival (PFS) or overall survival (OS). However, NIS emerged as predictive of the outcome with a 2-year PFS rate of 88% in the NIS ≤ 1 group and 49% in the NIS > 1 group and a significant effect in a multivariate analysis for both PFS (p = 0.049) and OS (HR = 9.61, CI 95% = [1.03-89.66], p = 0.04). Sarcopenia was not associated with adverse outcomes, but was related to NIS, which appeared to be an independent prognostic factor.


Olfactory capacity in anorexia nervosa: correlations with set-shifting ability.
The purpose of this study is to examine olfactory capacity in adults with anorexia nervosa (AN), in terms of odor identification and odor threshold and search for possible correlations between odor identification and cognitive flexibility in this population. Thirty-nine patients diagnosed with AN and 60 healthy participants, participated. Odor identification was assessed using the University Pennsylvania Smell Identification Test and a two alternative forced choice, ascending method with n-butanol was used to assess odor threshold. Cognitive flexibility was determined using the Intra/Extra-Dimensional Set-Shift test (IED), a subtest of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Patients with AN presented a poorer performance in odor identification compared with controls (p = 0.001). No differences were found in odor threshold, between the two groups. Patients with AN exhibited poor cognitive flexibility compared with controls (p = 0.003). A significant correlation between odor identification and cognitive flexibility was documented in AN (p = 0.01), but not in controls. Our findings suggest that olfactory capacity is altered in AN: Qualitative characteristics of olfaction were affected in patients with AN (lower odor identification), while there was no difference in quantitative characteristics (odor threshold) compared with controls. Furthermore, odor identification in AN was correlated to cognitive flexibility. Level III: case-control analytic study.


Neuroprotective effects of gabaergic phenols correlated with their pharmacological and antioxidant properties.
Various investigations have demonstrated the protective capacity of general anesthetics as neuroprotective agents. The effects of propofol against ischemia are known to reside in its antioxidant properties and its GABAergic activity. Other aromatic alcohols have also been reported as able to protect neurons against oxidative damage. The aim of this work is to evaluate the potential neuroprotective effect of some phenols, structurally analogues of propofol, with proven GABAergic activity. These phenols include the naturally occurring compounds thymol, carvacrol and eugenol, the synthetic product chlorothymol, and the most widely used intravenous anesthetic, propofol, as a reference compound. Taking primary cultures of cortical neurons as a suitable model to evaluate cellular protection against oxidative damage, we developed an injury model to test potential neuroprotective activity. The intracellular hydroperoxides were also determined. The results showed that no compound decreased cell viability at concentrations where they were active on the GABAA receptor. In neuroprotection tests, some phenols and Vit E showed a partial protective effect against the oxidative injury. These compounds induced a clear tendency to reduce H2O2 damage, comparing production of hydroperoxides, although these last changes were statistically non-significant. Testing the intracellular oxidation levels suggests that this partial protection exerted by propofol, thymol and chlorothymol may be mediated in some way by their antioxidant activities. However, this neuroprotection is not completely correlated with the antioxidant capacity, but it approaches their relative pharmacological potency, which could be interpreted as a final effect that would involve both activities.


Risk of retinal microembolism after off-pump and on-pump coronary artery bypass surgery.
In order to investigate the neuroprotective efficacy of off-pump coronary artery bypass surgery (OPCAB) over conventional on-pump coronary artery bypass surgery (CCAB), we have performed a prospective randomized study evaluating retinal circulation changes after OPCAB and CCAB. Twenty patients were randomized to OPCAB or CCAB. Retinal fluorescein angiography and 60 degrees black-and-white as well as color fundus photographs of both eyes of each patient were taken 1 to 24 h before and 5 to 6 days after the operation. Patients undergoing OPCAB had more severely stenosed carotid arteries (P=0.075), higher incidence of slightly diseased ascending aorta (P=0.087) and higher Northern New England Cardiovascular Study Group stroke risk score (P=0.075). Neither stroke nor transient ischemic attack occurred postoperatively in these patients. Inferotemporal retinal arterial embolization and microinfarction was detected in one patient after CCAB, but in none of the OPCAB group. The risk of retinal embolism can be minimized by the use of OPCAB and, most likely, by adequate epiaortic ultrasound scanning of the ascending aorta and avoiding clamping in case of severely diseased aorta.


Ag44 (EBT)26 (TPP)4 Nanoclusters With Tailored Molecular and Electronic Structure.
Although atomically precise metalloid nanoclusters (NCs) of identical size with distinctly different molecular structures are highly desirable to understand the structural effects on the optical and photophysical properties, their synthesis remains highly challenging. Herein, we employed phosphine and thiol capping ligands featuring appropriate steric effects and synthesized a charge-neutral Ag NC with the formula Ag44 (EBT)26 (TPP)4 (EBT: 2-ethylbenzenethiolate; TPP: triphenylphosphine). The single-crystal X-ray structure reveals that this NC has a hollow metal core of Ag12 @Ag20 and a metal-ligand shell of Ag12 (EBT)26 (TPP)4 . The presence of mixed ligands and long V-shaped metal-ligand motifs on this NC has resulted in an enhancement of the NIR-II photoluminescence quantum yield by >25-fold compared to an all-thiolate-stabilized anionic [Ag44 (SR)30 ]4- NC (SR: thiolate). Time-dependent density-functional calculations show that our Ag44 NC is an 18-electron superatom with a modulated electronic structure as compared to the [Ag44 (SR)30 ]4- anion, significantly influencing its optical properties.


Clinical features and development of Sepsis in Klebsiella pneumoniae infected liver abscess patients: a retrospective analysis of 135 cases.
Klebsiella pneumoniae is a primary pathogen of pyogenic liver abscess (PLA). However, little data are available on combination with sepsis. In this study, we aimed to evaluate the clinical characteristics and prognostic differences of PLA patients with sepsis. This retrospective cohort study was conducted to investigate 135 patients with confirmed Klebsiella pneumoniae-caused liver abscesses (KPLA) from a tertiary teaching hospital, from 2013 to 2019. The patients were divided into two groups, KPLA with sepsis and KPLA without sepsis. The demographic characteristics, clinical features as well as laboratory and microbiologic findings were analyzed. A total of 135 patients with KPLA were analyzed. The mean age of patients was 60.9 ± 12.7 years, and the percentage of men was 59.3%. Among them, 37/135 (27.4%) of patients had sepsis and the mortality rate was 1.5%. The most common symptom was fever (91.1%). KPLA patients with sepsis had a significantly higher proportion of frailty, diarrhea, fatty liver, chronic renal insufficiency, and hepatic dysfunction compared to KPLA patients without sepsis (p < 0.05). Antibiotic therapy and percutaneous drainage were most frequently therapeutic strategy. Furthermore, the incidences of sepsis shock and acute respiratory distress syndrome were higher in the sepsis group compared to the non-sepsis group. As for metastatic infections, the lung was the most common site. In addition, KPLA patients with sepsis showed respiratory symptoms in 11 patients, endophthalmitis in 4 patients, and meningitis in 1 patient. Our findings emphasize that KPLA patients combined with or without sepsis have different clinical features, but KPLA patients with sepsis have higher rates of complications and metastatic infections. Taken together, further surveillance and control of septic spread is essential for KPLA patients.


Thyroid function in children with short stature accompanied by isolated pituitary hypoplasia.
Few studies have focused on thyroid function in children with isolated pituitary hypoplasia (IPH). The purpose of this study was to investigate thyroid function in children with short stature accompanied by IPH and evaluate the values of thyroid function for the diagnosis of IPH. This was a retrospective observational study. A total of 100 children with short stature accompanied by IPH were enrolled. Among them, 68 children presenting with isolated growth hormone deficiency (IGHD) were chosen as the IPH group. Sixty-eight age-matched and sex-matched IGHD children without pituitary abnormalities were chosen as the control group. Clinical, hormonal, and imaging parameters were analyzed. The diagnostic value of thyroid function for IGHD children with IPH was evaluated. Children in the IPH group had significantly lower height standard deviation score (HSDS), HSDS-target height standard deviation score (THSDS), free thyroxine (FT4), insulin-like growth factor-1 standard deviation score (IGF-1SDS), and pituitary height than the control subjects (p = 0.027, p = 0.033, p < 0.001, p = 0.03, and p < 0.001, respectively). The value of the area under the curve (AUC) was 0.701 (95% CI 0.614-0.788, p < 0.001) when the cut-off value for FT4 was ≤ 16.43 pmol/L and the sensitivity and specificity were 72.1 and 61.8%, respectively. FT4 levels were positively correlated with FT3, GH peak, and IGF-1 SDS levels in all children with short stature accompanied by IPH (p < 0.001, p = 0.009, and p = 0.01, respectively). IGHD children with IPH had lower FT4 levels than IGHD children without pituitary abnormalities. FT4 levels may have diagnostic value for IGHD children with IPH.


Plain films are not accurate in planning internal fixation in vancouver type B1 periprosthetic femoral fractures and in distinguishing between subtypes B1 And B2.
While few studies analysed the diagnostic validity of preoperative radiographs in distinguishing between Vancouver type B1 and B2 periprosthetic femoral fractures (PFFs), no investigation has been conducted to assess the degree of diagnostic validity of preoperative radiographs in identifying the fracture course and planning the most appropriate treatment. We analysed the diagnostic validity of radiographs in detecting the fracture course and stem stability in Vancouver type B PFFs. Vancouver type B PFFs with different fracture courses were randomly performed in 36 dried cadaveric femurs in which a femoral broach had previously been implanted. Radiographic images, taken in the coronal and sagittal views, were analysed by 5 orthopaedic surgeons and 2 radiologists who were asked to reproduce the fracture course and to evaluate stem stability. A scoring system was used to determine the injured femoral cortex correctly identified by the examiners. The identification of the fracture course was scored as poor in 52.4% and 56.%, fair in 23% and 23.4% and good in 24.6% and 19.8%, The identification of the fracture course in the coronal and axial vies radiographs was scored in coronal and axial view radiographs respectively. There was no significant difference in the average score obtained by senior and young examiners. In the coronal plane, the fracture course was poorly identified by all examiners in 11 (30.5%) femurs and by 5 or more examiners in 17 (47%). The fracture course was correctly identified by 5 or more examiners in 8 femurs (22%). A vertical fracture involving an emidiaphysis was found in 8 of the 11 femurs in which the PFF was poorly diagnosed by all examiners. Stem instability was correctly diagnosed in 45% of cases. In type B PFFs preoperative radiographs show a reduced diagnostic validity in identifying the fracture course and, hence, in planning a correct treatment. Potentially unstable vertical fractures involving an emidiaphysis are likely to be poorly diagnosed since most of the fracture course is hidden by the femoral stem. In cementless stems the diagnostic validity of radiographs in diagnosing between Vancouver type B1 and B2 seems to be lower than that reported for cemented stems.


Epidemiology of injecting drug use, prevalence of injecting-related harm, and exposure to behavioural and environmental risks among people who inject drugs: a systematic review.
People who inject drugs are exposed to various and changing risk environments and are at risk of multiple harms related to injecting drug use (IDU). We aimed to undertake a global systematic review of the prevalence of IDU, key IDU-related harms (including HIV, hepatitis C virus [HCV], and hepatitis B virus [HBV] infection and overdose), and key sociodemographic characteristics and risk exposures for people who inject drugs. We systematically searched for data published between Jan 1, 2017, and March 31, 2022, in databases of peer-reviewed literature (MEDLINE, Embase, and PsycINFO) and grey literature as well as various agency or organisational websites, and disseminated data requests to international experts and agencies. We searched for data on the prevalence, characteristics, and risks of people who inject drugs, including gender, age, sexuality, drug-use patterns, HIV, HCV, and HBV infections, non-fatal overdose, depression, anxiety, and injecting-related disease. Additional data were extracted from studies identified in our previous review. Meta-analyses were used to pool the data where multiple estimates were available for a country. We present country, regional, and global estimates for each variable examined. We screened 40 427 reports published between 2017 and 2022, and the 871 eligible reports identified were added to the 1147 documents from the previous review. Evidence of IDU was documented in 190 of 207 countries and territories, and 14·8 million people (95% uncertainty interval [UI] 10·0-21·7) aged 15-64 years globally were estimated to inject drugs. Existing evidence suggests that there might be 2·8 million (95% UI 2·4-3·2) women and 12·1 million (95% UI 11·0-13·3) men who inject drugs globally, and that 0·4% (95% CI 0·3-1·3) of people who inject drugs identify as transgender. The amount of available data on key health and social risks among people who inject drugs varied widely across countries and regions. We estimated that 24·8% (95% CI 19·5-31·6) of people who inject drugs globally had experienced recent homelessness or unstable housing, 58·4% (95% CI 52·0-64·8) had a lifetime history of incarceration, and 14·9% (95% CI 8·1-24·3) had recently engaged in sex work, with substantial geographical variation. Injecting and sexual risk behaviour varied considerably geographically, as did risks of harms. Globally, we estimated that 15·2% (95% CI 10·3-20·9) of people who inject drugs are living with HIV, 38·8% (95% CI 31·4-46·9) have current HCV infection, 18·5% (95% CI 13·9-24·1) have recently overdosed, and 31·7% (95% CI 23·6-40·5) have had a recent skin or soft tissue infection. IDU is being identified in a growing number of countries and territories that comprise more than 99% of the global population. IDU-related health harms are common, and people who inject drugs continue to be exposed to multiple adverse risk environments. However, quantification of many of these exposure and harms is inadequate and must be improved to allow for better targeting of harm-reduction interventions for these risks. Australian National Health and Medical Research Council.


The effects of geometric and threshold definitions on cortical bone metrics assessed by in vivo high-resolution peripheral quantitative computed tomography.
This study evaluates in vivo methods for calculating cortical thickness (Ct.Th) with respect to sensitivity to tissue-level changes in mineralization and the ability to predict whole-bone mechanical properties. Distal radial and tibial images obtained from normal volunteers using high-resolution peripheral quantitative computed tomography (HR-pQCT) were segmented using three thresholds including the manufacturer default and +/-5% in terms of equivalent mineral density. Ct.Th was determined in two ways: using a direct three-dimensional (3D) method and using an annular method, where cortical bone volume is divided by periosteal surface area. D(comp) (mg HA/cm(3)) was calculated based on the mean density-calibrated linear attenuation values of the cortical compartment. Finite element analysis was performed to evaluate the predictive ability of the annular and direct Ct.Th methods. Using the direct 3D method, a +/-5% change in threshold resulted in a 2% mean difference in Ct.Th for both the radius and tibia. An average difference of 5% was found using the annular method. The change in threshold produced changes in D(comp) ranging 0.50-1.56% for both the tibia and radius. Annular Ct.Th correlated more strongly with whole-bone apparent modulus (R(2)=0.64 vs. R(2)=0.41). Both thickness calculation methods and threshold selection have a direct impact on cortical parameters derived from HR-pQCT images. Indirectly, these results suggest that moderate changes in tissue-level mineralization can affect cortical measures. Furthermore, while the direct 3D Ct.Th method is less sensitive to threshold effects, both methods are moderate predictors of mechanical strength, with the annular method being the stronger correlate.


Intra-patient comparison of physiologic 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia in prostate cancer patients: a pictorial essay.
Recent studies reported metabolic uptake in at least one of the evaluated ganglia in 98.5% of patients undergoing 68Ga -PSMA-11 and in 96.9% of patients undergoing 18F-DCFPyL PET/CT examination. We have observed different patterns of ganglion visualization with 18F-DCFPyL compared to 68Ga-PSMA-11. This includes more frequent visualization of cervical and sacral ganglia, which may be attributable to better imaging characteristics with 18F PET imaging. This pictorial essay is to illustrate and compare, in the same patient, various representative cases of 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia at different anatomic locations, with different patterns and distribution of metabolic activity. Reading physicians should be aware of the frequently encountered and occasionally different physiologic uptake of 68Ga-PSMA-11 and 18F DCFPyL in different ganglia.


Donor fibroblast chimerism in the pathogenic fibrotic lesion of human chronic graft-versus-host disease.
Tissue atrophy and excessive fibrosis are prominent histologic features of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation, but the underlying mechanism remains unknown. The current study was undertaken to investigate whether the increase in fibroblasts at the site of pathogenic fibrosis originated from transplanted donor cells in patients with chronic GVHD. Lacrimal gland biopsy specimens were obtained from nine patients with chronic GVHD. The male-specific sequences detected by fluorescein in situ hybridization (FISH) and in situ hybridization (ISH) were used as markers for the donor cells in seven female patients who had received a transplant from male donors. Primary fibroblast cultures were generated from lacrimal gland biopsy specimens and examined for mismatched genetic markers between recipients and donors. In lacrimal gland specimens obtained from seven female patients who received a sex-mismatched transplant, 13.4% to 26.7% of CD34+ fibroblasts that accumulated in the fibrotic lesion were donor derived, as determined by FISH for the Y-chromosome. The male-specific mRNA was also detected in the lacrimal gland fibroblasts by ISH. Primary lacrimal gland fibroblast cultures were generated from four patients with chronic GVHD and further examined for mismatched genetic markers between recipients and donors. As a result, the presence of donor origin of the fibroblasts was demonstrated by detecting the Y-chromosome sequence and donor-specific microsatellite genetic markers. These findings together indicate the chimeric status of accumulated CD34+ fibroblasts in the lacrimal gland of patients with chronic GVHD. Fibroblasts originating from circulating donor-derived precursors may participate in the excessive fibrosis in these patients.


First-Line Durvalumab Plus Platinum-Etoposide Versus Platinum-Etoposide for Extensive-Stage Small-Cell Lung Cancer: A Cost-Effectiveness Analysis.
The aim of the present study was to evaluate the cost-effectiveness of durvalumab plus platinum-etoposide versus platinum-etoposide as first-line treatments for small-cell lung cancer from the perspective of the US payer. This study established a partition survival model for three health states, metastasis probability, and safety data based on the CASPIAN clinical trial. The health utility value was mainly derived from the published literature. Only direct medical costs were considered. Sensitivity analyses were conducted to assess the robustness of the incremental cost per quality-adjusted life year (QALY). Durvalumab plus platinum-etoposide increased QALY by 0.220 compared to that observed with platinum-etoposide only. The cost increased by $78,198.75 and the incremental cost per QALY increased by $355,448.86. One-way and probability sensitivity analyses indicated that the model parameters varied within a limited range and had no significant effect on the results. Although durvalumab plus platinum-etoposide can improve quality of life, it also substantially increases the cost of medical treatment. Under a willingness-to-pay threshold of $100,000, durvalumab does not have a cost-effective comparative advantage.


Combined effect of a lecithin and a bile salt on pancreatic lipase activity.
Lipolysis is regulated by the presence of amphiphilic compounds such as bile salts and lecithin, which are adsorbed at the triglyceride-water interface and therefore influence the approach of water-soluble pancreatic lipase to its insoluble substrate (emulsified triglycerides). The partition of bile salts between the lipid and the aqueous phase is of prime importance in the expression of lipase activity. Lipase activity was determined as a function of different combinations of concentrations of deoxycholate and dipalmitoylphosphatidyl choline. From zeta-potential measurements, it is evident that lecithin affects the partition of bile salts, most probably by displacing deoxycholate molecules. Our results indicate that lecithin cannot be classified a priori as inhibitor or activator of pancreatic lipase. As an amphiphilic compound, lecithin exerts a synergistic effect with bile salts via the formation of mixed micelles. The final effect on lipolysis depends on the ratio of lecithin to bile salt: low ratios enhance enzyme activity, whereas high ratios lead to inhibition.


Behavioral responses of three freshwater planaria species to light, visual and olfactory stimuli: Setting the stage for further ecotoxicological studies.
Planarians are freshwater flatworms commonly used as environmental bioindicator due to their sensitivity of response and their ease of culturing in lab. Nevertheless, to date, very few studies describing their behavior have been led. This work aims to fill the literature gap by providing preliminary results through six behavioral challenges (locomotion, exploration, light stress, planarian light/dark test, shoaling and foraging) conducted with three different species Dugesia tigrina, Schmidtea mediterranea and Schmidtea polychroa. The behavioral responses of every species in each of these six assays were recorded and differences between species were highlighted, depending on the assays and conditions. Schmidtea polychroa is less active than the two others and had the highest light aversion. Reactions observed in response to diverse and realistic stimuli helped us to select the most suitable tests and choose the species that seem the most appropriate for future ecotoxicological and neurophysiological tests. Four tests - out of the six tested- seem reliable in order to standardize planarian behavioral tests.


Long-term outcome of cerebral amyloid angiopathy-related hemorrhage.
The long-term functional outcome of cerebral amyloid angiopathy-related hemorrhage (CAAH) patients is unclear. We sought to assess the long-term functional outcome of CAAH and determine the prognostic factors associated with unfavorable outcomes. We enrolled consecutive CAAH patients from 2014 to 2020 in this observational study. Baseline characteristics and clinical outcomes were presented. Multivariable logistic regression analysis was performed to identify the prognostic factors associated with long-term outcome. Among the 141 CAAH patients, 76 (53.9%) achieved favorable outcomes and 28 (19.9%) of them died at 1-year follow-up. For the longer-term follow-up with a median observation time of 19.0 (interquartile range, 12.0-26.5) months, 71 (50.4%) patients obtained favorable outcomes while 33 (23.4%) died. GCS on admission (OR, 0.109; 95% CI, 0.021-0.556; p = 0.008), recurrence of ICH (OR, 2923.687; 95% CI, 6.282-1360730.14; p = 0.011), WML grade 3-4 (OR, 31.007; 95% CI, 1.041-923.573; p = 0.047), severe central atrophy (OR, 4220.303; 95% CI, 9.135-1949674.84; p = 0.008) assessed by CT was identified as independent predictors for long-term outcome. Nearly 50% of CAAH patients achieved favorable outcomes at long-term follow-up. GCS, recurrence of ICH, WML grade and cerebral atrophy were identified as independent prognostic factors of long-term outcome.


[Risk Factors Associated with Venous Thromboembolism after Lung Cancer Surgery: A Single-center Study].
The Previous study has indicated that the incidence of venous thromboembolism (VTE) after lung cancer surgery is not uncommon. The aim of this study is to analyze the risk factors of postoperative VTE in lung cancer patients and provide a clinical basis for further prevention and treatment of VTE. This study was a single-center study. From July 2016 to December 2017, all patients with lung cancer who underwent surgery in our department were enrolled into this study. Except routine preoperative examinations, lower extremity Doppler ultrasound was performed in all patients before and after surgery to determine whether there was any newly developed deep venous thrombosis (DVT). Patients did not receive any prophylactic anticoagulant therapy before and after surgery. Patients were then divided into VTE group and control group according to whether VTE occurred after operation. Baseline data, surgical related data (surgery type, surgical procedure, etc.) and tumor pathological data (pathological type, vascular infiltration, pathological staging, etc.) were compared between the two groups. According to the inclusion criteria, a total of 339 patients undergoing lung cancer surgery were analyzed. There were 166 males and 173 females with an age range of 23-86 years. A total of 39 patients developed VTE after surgery, the incidence rate of postoperative VTE was 11.5%. Comparing the age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA), smoking status, underlying diseases, etc, there were no significant differences in other indicators except for significant differences in age; comparison between preoperative blood routine, blood biochemistry, coagulation, tumor markers, lung function, lower extremity venous ultrasound, preoperative carcinoembryonic antigen (CEA) levels, preoperative D-dimer levels, there were significant differences in lung function and lower extremity intermuscular vein expansion ratio. There were no significant differences in other indexes between the two groups. The duration of surgery, surgical procedure, bleeding volume, pathological type, pathological stage, vascular invasion, were compared between the two groups. There were statistical differences in surgical methods (thoracic vs thoracoscopic) and bleeding volume. There were no significant differences in other indicators. Univariate analysis showed that age, preoperative CEA level, preoperative D-dimer level, poor pulmonary function, lower extremity intermuscular vein dilation ratio, thoracotomy rate, length of surgery, and amount of bleeding were significantly risk factors (P<0.05). There were no significant correlations between pathological stage and pathological type and VTE. Multivariate logistic regression analysis showed that forced expiratory volume in one second (FEV1), surgical approach, and lower extremity intermuscular vein dilatation were independent risk factors for postoperative VTE in patients with lung cancer (P<0.05). The results of this study suggest that FEV1, surgical procedures, and lower extremity intermuscular vein dilation are independent risk factors for postoperative VTE in patients with lung cancer.


Yersinia enterocolitica in food hygiene.
Yersinia enterocolitica and Yersinia enterocolitica-like bacteria constitute a fairly heterogenous group of bacteria which includes both well-established pathogens and a range of environmental strains which are ubiquitous in terrestrial and freshwater ecosystems. Pathogenic significance in man is mainly associated with a few serogroups (O:3, O:9, O:8, O:5,27). The pathogenic serogroups show different geographical distributions. The development of isolation procedures which clearly differentiate pathogenic from non-pathogenic variants has been difficult. Of special significance in food hygiene is the ability of Y. enterocolitica to grow in refrigerated foods. There is strong indirect evidence that pigs and food products of porcine origin are the major sources for human infection with Y. enterocolitica serogroups O:3 and O:9, the dominant human pathogens in most parts of the world. The reservoir(s) for serogroup O:8, which prevails in the U.S.A., is uncertain. The pig is the only animal consumed by man which regularly harbours pathogenic Y. enterocolitica. Improved isolation methods and DNA colony hybridization using genetic probes has indicated that the prevalence of pathogenic Y. enterocolitica in pork products is substantially higher than previously suggested. Prevention and control measures should focus on information of people involved in food processing and preparation and on the improvement of hygiene during slaughtering of swine. Important critical control points at the stage of slaughter are: (i) circumanal incision and removal of intestines, (ii) excision of the tongue, pharynx, and particularly the tonsils, (iii) post-mortem meat inspection procedures which involve incision of the mandibular lymph nodes, and (iv) deboning of head meat.


Mild hypoxia disrupts recollection, not familiarity.
Yonelinas et al. (2002) found that hypoxic patients exhibited deficits in recollection that left familiarity relatively unaffected. In contrast, Manns, Hopkins, Reed, Kitchener, and Squire (2003) studied a group of hypoxic patients who suffered severe and equivalent deficits in recollection and familiarity. We reexamine those studies and argue that the discrepancy in results is likely due to differences in the hypoxic groups that were tested (i.e., differences in amnestic severity, subject sampling methods, and patient etiology). Yonelinas et al. examined memory in 56 cardiac arrest patients who suffered a brief hypoxic event, whereas Manns et al. examined a group of severely amnesic patients that consisted of 2 cardiac arrest patients, 2 heroin overdose patients, 1 carbon monoxide poisoning patient, and 2 patients with unknown etiologies. We also consider an alternative explanation proposed by Wixted and Squire (2004), who argued that the two patient groups suffered similar deficits, but that statistical or methodological artifacts distorted the results of each of Yonelinas et al.'s experiments. A consideration of those results, however, indicates that such an explanation does not account for the existing data. All of the existing evidence indicates that recollection, but not familiarity, is disrupted in mild hypoxic patients. In more severe cases of hypoxia, or those with more complex etiologies such as heroin overdose, more profound deficits may be observed.


The expression of differentiated functions in somatic cell hybrids: retention and activation of C3 production.
Rat and mouse fibroblasts which do not secrete the third component of complement (or secrete it at a very low rate), were respectively hybridized with mouse and rat hepatoma cells which actively produce C3. These interspecific hybrids actively secrete both mouse and rat C3. The production of C3 coded by the hepatoma cell genome is thus retained, but in addition, the secretion of C3 coded by the fibroblast genome is activated. On the other hand, intraspecific hybrids have been isolated from normal diploid C3 producing cells and non-producing cells. These cell hybrids also retain the capacity to secret C3. Retention of C3 production thus does not appear to be peculiar to hybrides derived from hepatoma cells.