Augmented Insulin and Leptin Resistance of High Fat Diet-Fed APPswe/PS1dE9 Transgenic Mice Exacerbate Obesity and Glycemic Dysregulation.
Alzheimer's disease (AD), a progressive neurodegenerative disease is highly associated with metabolic syndromes. We previously demonstrated that glycemic dysregulation and obesity are augmented in high fat diet (HFD)-treated APPswe/PS1dE9 (APP/PS1) transgenic mice. In the current study, the underlying mechanism mediating exacerbated metabolic stresses in HFD APP/PS1 transgenic mice was further examined. APP/PS1 mice developed insulin resistance and, consequently, impaired glucose homeostasis after 10 weeks on HFD. [18F]-2-fluoro-2-deoxy-d-glucose ([18F]-FDG) positron emission tomography showed that interscapular brown adipose tissue is vulnerable to HFD and AD-related pathology. Chronic HFD induced hyperphagia, with limited effects on basal metabolic rates in APP/PS1 transgenic mice. Excessive food intake may be caused by impairment of leptin signaling in the hypothalamus because leptin failed to suppress the food intake of HFD APP/PS1 transgenic mice. Leptin-induced pSTAT3 signaling in the arcuate nucleus was attenuated. Dysregulated energy homeostasis including hyperphagia and exacerbated obesity was elicited prior to the presence of the amyloid pathology in the hypothalamus of HFD APP/PS1 transgenic mice; nevertheless, cortical neuroinflammation and the level of serum Aβ and IL-6 were significantly elevated. Our study demonstrates the pivotal role of AD-related pathology in augmenting HFD-induced insulin and leptin resistance and impairing hypothalamic regulation of energy homeostasis.


Vaginal birth after caesarean section: clinical and legal perspectives.
Vaginal birth after Caesarean section (VBAC) is currently the preferred method of delivery for pregnant women who have undergone 1 previous low transverse Caesarean section. This common practice warrants some reconsideration in light of recent clinical data on the risks associated with VBAC, and it is incumbent upon clinicians to ensure that women under their care are fully aware of these risks. Indeed, in some circumstances, an attempt at VBAC may be perceived by the courts to represent a negligent standard of care.


[Struma ovarii associated with Graves' disease].
Hyperthyroidism is defined as an excessive production of thyroid hormones by eutopic or ectopic mature thyroid tissue. The overall prevalence of hyperthyroidism is 1.2% and the most common cause is Graves' disease. Struma ovarii represents 1% of all ovarian tumors and is an uncommon cause of ectopic hyperthyroidism. It is benign in >90% of the cases; usually asymptomatic, and only 8% are presented with thyrotoxicosis, being rare its association with Graves' disease. We report the case of a patient with this association.


Design and Evaluation of Topical Antioxidant Nanogel Formulations.
Transdermal delivery of an active substance is promising, but a challenging option is available for local and systemic effects. The prolonged residence of formulation in the skin is important for topical delivery. In this study, it was aimed to develop a formulation that can overcome the stability and absorption problems of the vitamin C active substance by preparing nanogels. Nanogel-based materials have high drug loading capacity, biocompatibility, stability, and biodegradability, which are the key points to design a topical drug delivery system. Bovine serum albumin (BSA) and chitosan (CS) were used to prepare nanogels by a simple green self-assembly technique. Prepared nanogels were successfully used to entrap vitamin C, with an entrapment ratio between 86.08% ± 1.29% and 107.93% ± 1.04%. The studies started with vitamin C analysis and continued with characterization studies such as homogeneity, pH, viscosity, rheological properties, zeta potential, polydispersity index, particle size, and in vitro dissolution studies of nanogels. The antioxidant activities of the formulations were also tested by cell culture studies. The antioxidant activities of the nanogels were also tested by in vitro 2,2-diphenyl-1-picrylhydrazyl assay. Although topical vitamin C is effective in many ways, it has a risk of serious stability and absorption problems. The present work was aimed at developing pharmaceutically optimized topical nanogel formulations of vitamin C for antioxidant effect. An optimum nanogel formulation was composed of a 1:4 ratio of CS:BSA with (F19 formulation) in terms of entrapping vitamin C, formulation homogeneity, pH, viscosity, rheological properties, zeta potential, PI, particle size, in vitro dissolution and cell culture studies. The optimized formulation showed higher antioxidant efficacy in vitro than vitamin C. In conclusion, prepared topical nanogel of vitamin C was stable and could be used with promising potential for topical application.


Topical tacrolimus 0.03% ointment for intractable allergic conjunctivitis: an open-label pilot study.
To evaluate the feasibility of tacrolimus 0.03% dermatological ointment (Protopic) in the treatment of intractable allergic conjunctivitis. Twenty patients (mean age 10.8 years, range 6-26) with intractable allergic conjunctivitis were enrolled in an open-label study. Tacrolimus 0.03% ointment was applied into the conjunctival sac of both eyes twice daily for 8 weeks, followed by a 2-week washout period. Other ocular medications were discontinued. Conjunctivitis severity was recorded with a composite subjective/objective score (chemosis, tarsal papillary size, corneal staining, tearing, itching, and photophobia) at baseline, week 8, and after washout. Tacrolimus blood levels were measured at 2 weeks. Statistically significant improvement in all categories of the conjunctivitis score was observed between baseline and the week 8 examination (p < 0.001). Adverse events were limited to local burning in one patient who discontinued treatment. Blood tacrolimus levels were mostly undetectable. Application of tacrolimus 0.03% dermatological ointment into the conjunctival sac appears to be effective, well tolerated, and safe in the treatment of allergic conjunctivitis refractory to traditional treatment.


Relationship between the Thermal Denaturation and Gelling Properties of Legumin from Broad Beans.
The effects of NaCl and heating temperature on the gel-forming ability of legumin were studied. The addition of NaCl progressively increased the denaturation temperature of legumin. Heating to around the denaturation point, i.e., below the onset temperature (zone 1), between the onset and maximal temperatures (zone 2), between the maximal and final temperatures (zone 3), and above the final temperature (zone 4), affected both the gel-forming ability and gel properties. No gel was formed in zone 1, while the gel was harder in zone 3 than in zones 2 and 4. The gel hardness gradually decreased with increasing temperature in zone 4. Differences in the viscoelastic and microstructural properties between gels heated at various temperatures around the denaturation point were observed.


Yolk partitioning in embryos of the lizard, Calotes versicolor: maximize body size or save energy for later use?
The hatchlings of Calotes versicolor and other congeners retain residual yolk for immediate post-hatching needs. Excision of 8% yolk (approximately equal residual yolk) from the eggs resulted in smaller hatchlings when compared to those emerging from sham operated eggs. However, hatchlings in both groups retained the same amount of residual yolk. The findings suggest that residual yolk in hatchlings of C. versicolor is an important part of the energy budget set aside by developing embryos and that the advantages of large hatchling size are counter balanced by selection for residual yolk.


Proteomic Analysis of Soybean [Glycine max (L.) Merrill] Roots Inoculated with Bradyrhizobium japonicum Strain CPAC 15.
This research intended to analyze the expression pattern of proteins in roots of the Brazilian soybean cultivar Conquista when inoculated with Bradyrhizobium japonicum CPAC 15, a strain broadly used in commercial inoculants in Brazil. At ten days after bacterial inoculation, whole-cell proteins were extracted from roots and separated by 2-D gel electrophoresis. Comparative analysis revealed significant changes in the intensity of 37 spots due to the inoculation (17 up-regulated and 20 down-regulated proteins), identified by MALDI-TOF/TOF-TOF. Identified proteins were associated with COG functional categories of information storage and processing, cellular processes and signaling, metabolism, and also in the "poorly characterized" and "not in COG" categories. Among the up-regulated proteins, we identified sucrose synthase (nodulin-100), β-tubulin, rubisco activase, glutathione-S-transferase, a putative heat-shock 70-kDa protein, pyridine nucleotide-disulphideoxidoreductase and a putative transposase. Proteomic analysis allowed for the identification of some putative symbiotic functions and confirmed the main biological processes triggered in the nitrogen-fixing symbiosis with soybean.


Clinical Efficacy of Qili Qiangxin Capsule Combined with Western Medicine in the Treatment of Chronic Heart Failure: A Systematic Review and Meta-Analysis.
Qili Qiangxin capsule (QQC) is a formulation of traditional Chinese medicine commonly used for the treatment of heart failure in China. This meta-analysis aimed to assess the clinical efficacy of QQC combined with western medicine in the treatment of chronic heart failure (CHF). We conducted a systematic review and meta-analysis abided by the PRISMA guidelines. Literature search was conducted in the China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journals Database, PubMed, and Web of Science from inception to August 2020. A total of 52 eligible studies were obtained, and 42 of these studies were included in the meta-analysis. The results showed that, compared with western medicine alone, the combination of Qili Qingxin capsule and Western medicine treatment has better efficacy (metoprolol: RR: 1.24, 95%CI 1.14-1.34; carvedilol: RR: 1.24, 95%CI 1.14-1.34; trimetazidine: RR: 1.20, 95%CI: 1.12-1.27; sacubitril valsartan sodium: RR: 1.23, 95%CI: 1.11-1.36; sodium nitroprusside: RR: 1.33, 95%CI: 1.23-1.45; and bisoprolol: RR: 1.31, 95%CI: 1.15-1.49) and increased the level of LVEF, LVEDD, and 6MWT of patients with CHF and reduced the adverse effects and the level of HR, LVESD, BNP, and Hs-cTnT as well. However, there is high heterogeneity in the meta-analysis of LVEDV, BNP, NT-proBNP, Hs-cTnT, 6MWT, and adverse effects, and the methodological quality of the included studies was poor. Therefore, further studies with good methodological quality and large sample size are required to validate our findings. In our study, evidence suggests that Qili Qiangxin capsule combined with Western medicine may improve therapeutic effect and the quality of life of patients with CHF.


Mesoporous SnO2 Nanotubes via Electrospinning-Etching Route: Highly Sensitive and Selective Detection of H2S Molecule.
We report the facile synthesis of thin-walled SnO2 nanotubes (NTs) with numerous clustered pores (pore radius 6.56 nm) and high surface area (125.63 m2/g) via selective etching of core (SiO2) region in SiO2-SnO2 composite nanofibers (NFs), in which SnO2 phase preferentially occupies the shell while SiO2 is concentrated in the center of the composite NFs. The SiO2-etched SnO2 NTs are composed of ultrasmall crystallites (∼6 nm in size) originating from crystal growth inhibition by small SiO2 domains, which are partially segregated in the polycrystalline SnO2 shell during calcination. These features account for efficacious diffusion and innumerable active sites, which maximize interaction between background gas (air) and analyte gas (H2S). Evaluation of gas-sensing performance of the porous SnO2 NTs before and after decorating the exterior and interior walls with Pt nanoparticles (NPs) reveals exceptional selectivity and superior response (Ra/Rg) of 154.8 and 89.3 to 5 and 1 ppm of H2S, respectively. Excellent gas-sensing characteristics are attributed to the porous topography, nanosized crystallites, high surface area, and the catalytic activity of Pt/PtOx NPs.


Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised hosts.
Thirty-one immunocompromised patients with severe cytomegalovirus (CMV) disease were treated with intravenous ganciclovir. Twenty-one patients had received transplants--15 bone marrow recipients, five renal allograft recipients, and one liver transplant recipient--while the other ten were immunocompromised due to acquired immunodeficiency syndrome (six), hematologic malignancies (three), and systemic lupus erythematosus (one). They presented with one or more of the following syndromes: CMV pneumonitis (19), CMV of the gastrointestinal tract (six), CMV retinitis (seven), and CMV hepatitis (three). Seventeen (55%) of 31 patients demonstrated clinical improvement during ganciclovir therapy, with the best response seen in the transplant recipients. Viremia ceased in 14 (93.3%) of 15 patients after a mean of 4.7 days of therapy; viruria ceased in eight (53.3%) of 15 patients after a mean of 11 days of therapy. Ganciclovir plasma concentrations at a dosage of 2.5 mg/kg/three times a day were as follows: mean peak, 16.04 mumol/L; mean trough, 2.38 mumol/L. Neutropenia occurred in 11 (35%) of 31 patients and in nine (60%) of 15 bone marrow transplant recipients. We conclude that ganciclovir exerted an antiviral effect against CMV and may play a role in the treatment of CMV disease in patients with depressed immunity, especially bone marrow and organ transplant recipients.


Occurrence of immune cells in the intestinal wall of Squalius cephalus infected with Pomphorhynchus laevis.
A sub-population of 34 specimens of chub, Squalius cephalus, was sampled from the River Brenta (Northern Italy) and examined for ecto- and endo-parasites. Pomphorhynchus laevis (Acanthocephala) was the only enteric helminth encountered. Immunofluorescence and ultrastructural studies were conducted on the intestines of chub. Near the site of parasite's attachment, mucous cells, mast cells (MCs), neutrophils and rodlet cells (RCs) were found to co-occur within the intestinal epithelium. The numbers of mucous cells, MCs and neutrophils were significantly higher in infected fish (Mann-Whitney U test, p < 0.05). Dual immunofluorescence staining with the lectin Dolichos Biflorus Agglutinin (DBA) and the macrophage-specific MAC387 monoclonal antibody, with parallel transmission electron microscopy, revealed that epithelial MCs often made intimate contact with the mucous cells. Degranulation of a large number of MCs around the site of the acanthocephalan's attachment and in proximity to mucous cells was also documented. MCs and neutrophils were abundant in the submucosa. Immune cells of the intestinal epithelium have been described at the ultrastructural level and their possible functions and interactions are discussed.


Stem Cell Research Lab Resource: Stem Cell LineInduced pluripotent stem cell (iPSC) line MLi-003A derived from an individual with the maximum number of filaggrin (FLG) tandem repeats.
We have generated MLi003-A, a new induced pluripotent stem cell (iPSC) line derived from hair follicle keratinocytes of a healthy male characterized with a maximum number of filaggrin tandem repeats, making this iPSC line the best control for studies on skin barrier function. The characterization of the MLi003-A cell line consisted of molecular karyotyping, high-throughput array-based sequencing composed of Fluidigm microfluidics technology and next-generation sequencing of the filaggrin alleles, and pluripotency and differentiation potentials testing by immunofluorescence of associated markers both in vitro and in vivo. The MLi-003A line has been also tested for ability to differentiate into keratinocytes.


Methods and applications of the audibility index in hearing aid selection and fitting.
During the first half of the 20th century, communications engineers at Bell Telephone Laboratories developed the articulation model for predicting speech intelligibility transmitted through different telecommunication devices under varying electroacoustic conditions. The profession of audiology adopted this model and its quantitative aspects, known as the Articulation Index and Speech Intelligibility Index, and applied these indices to the prediction of unaided and aided speech intelligibility in hearing-impaired listeners. Over time, the calculation methods of these indices-referred to collectively in this paper as the Audibility Index-have been continually refined and simplified for clinical use. This article provides (1) an overview of the basic principles and the calculation methods of the Audibility Index, the Speech Transmission Index and related indices, as well as the Speech Recognition Sensitivity Model, (2) a review of the literature on using the Audibility Index to predict speech intelligibility of hearing-impaired listeners, (3) a review of the literature on the applicability of the Audibility Index to the selection and fitting of hearing aids, and (4) a discussion of future scientific needs and clinical applications of the Audibility Index.


Altered effective connectivity of resting state networks by acupuncture stimulation in stroke patients with left hemiplegia: A multivariate granger analysis.
The aim of this study was to explore the response feature of resting-state networks (RSNs) of stroke patients with left hemiplegia by acupuncture stimulation.Nineteen stroke patients with left hemiplegia and 17 controls were recruited in this study. Resting-state functional magnetic resonance imaging data before and after acupuncture were acquired using magnetic scanning. The independent component analysis (ICA) was employed to extract RSNs related to motion, sensation, cognition, and execution, including sensorimotor network (SMN), left and right frontoparietal network (LFPN and RFPN), anterior and posterior default mode network (aDMN, pDMN), visual network (VN), and salience network (SN). Granger causality method was used to explore how acupuncture stimulation affects the causality between intrinsic RSNs in stroke patients. Compared with healthy subjects, stroke patients presented the more complex effective connectivity. Before acupuncture stimulation, LFPN inputted most information from other networks while DMN outputted most information to other networks; however, the above results were reversal by acupuncture. In addition, we found aDMN reside in between SMN and LFPN after acupuncture.The finding suggested that acupuncture probably integrated the effective connectivity internetwork by modulating multiple networks and transferring information between LFPN and SMN by DMN as the relay station.


The distally based radial forearm fasciosubcutaneous flap with preservation of the radial artery: an anatomic and clinical approach.
The axial-pattern reverse radial forearm fasciocutaneous flap has become one of the primary flaps for reconstruction of soft-tissue defects of the hand. The two main disadvantages of this flap are (1) sacrifice of a major artery that may possibly jeopardize hand viability and (2) morbidity and appearance of the donor site. In an effort to overcome these drawbacks, an anatomic study of a distally based radial forearm fasciosubcutaneous flap with preservation of the radial artery was conducted. Seventeen fresh cadaver forearms were dissected to investigate the contribution of the distal radial artery and its superficial and deep branches to the fasciosubcutaneous plexus of the forearm. The blood supply to the radial forearm fasciosubcutaneous tissue was found to emanate from 6 to 10 septocutaneous perforators of the distal radial artery in the vicinity of the anatomic snuff box that "fan out" at the level of the deep fascia to form a rich plexus supplying the forearm fascia, subcutaneous tissue, and skin. There appeared to be a definite directional component, with the arterioles running longitudinally along the intermuscular septum. The deep fascia and subcutaneous tissue were found to have their own venous system accompanying the small perforating arterioles. Encouraged by these findings, we proceeded to utilize this fasciosubcutaneous flap for coverage of the thumb-index web space (three patients), the dorsum of the hand (two patients), and both the palmar and dorsal aspects of the hand (one patient). Five flaps had almost complete survival. The largest flap in our series suffered significant loss. Minor skin-graft loss occurred in a few cases, and we now delay skin grafting for several days. The distally based radial forearm fasciosubcutaneous flap with preservation of the radial artery can be a very useful and reliable alternative for repairing soft-tissue defects of the hand, obviating the need for the classic fasciocutaneous flap or even a free flap. This flap not only preserves the radial artery, which is essential in cases where only the radial artery is functioning, such as following severe hand injuries, but also provides a more acceptable donor site.


[Sudden blindness: consider Leber's hereditary optic neuropathy].
In 3 young male patients, aged 10, 19 and 21 years respectively, sequential, severe, painless bilateral visual loss occurred. Ophthalmological examination revealed no other abnormalities and this delayed the diagnosis Leber's hereditary optic neuropathy (LHON). LHON is a mitochondrial genetic disease characterised by bilateral acute or subacute painless loss of central vision. LHON causes blindness, predominantly in young adult males but less frequently in women and children as well. Occasionally, LHON is associated with other neurological and cardiac changes. The first patient recovered his vision within 2 years, but the other 2 remained blind. All 3 patients had a m.11778G > A mutation in the mitochondrial DNA (mtDNA). Over 95% of LHON cases are primarily the result of one of three mitochondrial DNA point mutations. In addition, analysis of patients grouped according to mtDNA mutation has demonstrated differences in both the clinical features of visual failure and in recurrence risks for relatives that are associated with each of the pathogenic mtDNA mutations. Depending on the type of mutation, recovery of vision occurs in 4-58% of the patients. Whilst pathogenic mtDNA mutations are required for the development of LHON, other factors must be responsible for the variable penetrance and male predominance. Familiarity with the clinical spectrum of LHON is necessary for early diagnosis. There is no proven treatment.


Involvement in Fertilization and Expression of Gamete Ubiquitin-Activating Enzymes UBA1 and UBA6 in the Ascidian Halocynthia roretzi.
The extracellular ubiquitin-proteasome system is involved in sperm binding to and/or penetration of the vitelline coat (VC), a proteinaceous egg coat, during fertilization of the ascidian (Urochordata) Halocynthia roretzi. It is also known that the sperm receptor on the VC, HrVC70, is ubiquitinated and degraded by the sperm proteasome during the sperm penetration of the VC and that a 700-kDa ubiquitin-conjugating enzyme complex is released upon sperm activation on the VC, which is designated the "sperm reaction". However, the de novo function of ubiquitin-activating enzyme (UBA/E1) during fertilization is poorly understood. Here, we show that PYR-41, a UBA inhibitor, strongly inhibited the fertilization of H. roretzi. cDNA cloning of UBA1 and UBA6 from H. roretzi gonads was carried out, and their 3D protein structures were predicted to be very similar to those of human UBA1 and UBA6, respectively, based on AlphaFold2. These two genes were transcribed in the ovary and testis and other organs, among which the expression of both was highest in the ovary. Immunocytochemistry showed that these enzymes are localized on the sperm head around a mitochondrial region and the follicle cells surrounding the VC. These results led us to propose that HrUBA1, HrUBA6, or both in the sperm head mitochondrial region and follicle cells may be involved in the ubiquitination of HrVC70, which is responsible for the fertilization of H. roretzi.


Anchoring Iodine to N-Doped Hollow Carbon Fold-Hemisphere: Toward a Fast and Stable Cathode for Rechargeable Lithium-Iodine Batteries.
Rechargeable lithium-iodine batteries with abundant raw materials and low cost are promising electrochemical energy storage systems. Herein, we demonstrate that anchoring iodine to N-doped hollow carbon fold-hemisphere (N-FHS) is highly efficient to overcome slow kinetics and low stability of iodine cathode in lithium-iodine batteries. For the first time, significant effects of carbon framework architecture on the lithium storage performance of iodine cathode are studied in detail. Notably, the fold-hemisphere (N-FHS) is more effective than the similar architectures, such as hollow sphere (N-S) or hemisphere (N-HS), in modifying slow ion transport capability and fast structure deterioration. The superior property of iodine@N-FHS is associated with its highly porous structure and strong interconnection to iodine. The iodine deterioration mechanism in lithium-iodine battery is analyzed, and the deterioration processes of iodine in different carbon frameworks during cycling are investigated. This work opens a new avenue to solve the key problems in lithium-iodine batteries, allowing it an important candidate for energy storage.


[Osteoplastic hip buttress in the treatment of osteoarthritis of the hip].
The results of 40 acetabuloplasties of the hip for osteoarthritis have been studied over a follow-up period of 6 months to 7 years. 12 patients have been treated by shelf arthroplasty alone and 26 by the same operation combined with intertrochanteric osteotomy. These operations, which are suitable for use in patients too young for a total hip prosthesis, give very satisfactory results in 80% of the cases, but the patients must be carefully selected. The clinical and radiological criteria on which this choice is based, and the technical peculiarities of the operation, are described.


High recurrence rate of Barrett's epithelium during long-term follow-up after argon plasma coagulation.
Several studies have shown that argon plasma coagulation (APC) combined with proton-pump inhibitor (PPI) therapy is a suitable procedure to eradicate Barrett's epithelium for a short-term follow-up. The real impact of this kind of management with respect to cancer risk and durability of squamous regeneration remains unclear. We present the follow-up data for up to 51 months after eradication of Barrett's mucosa. In 1998-2001, 25 patients with Barrett's esophagus were included in a prospective study. After baseline documentation, Barrett's epithelium was treated with repeated APC until complete squamous restoration was reached. Thereafter, all patients were continuously treated with high-dose PPIs. Each patient underwent a median of four APC sessions. Twenty-one (84%) of the patients had complete squamous regeneration at the end of treatment. During a follow-up of up to 51 months, Barrett's epithelium was found to have recurred in 14/21 (66%) patients. Including the patients with initially incomplete squamous restoration, a long-lasting and complete effect was achieved in only 7 patients (28%) after a mean follow-up period of 30 months. So far, it is still not proven whether coagulation-induced squamous regeneration reduces the risk of Barrett's carcinoma. Furthermore, the high relapse rate, the procedure-related risk, and the high costs incurred preclude the routine use of APC for the treatment of non-dysplastic Barrett's esophagus. The different recurrence rates between published studies may be due to technical differences and PPI schedule. We suggest that optimal conditions for the procedure must be defined before further studies are undertaken.


HCN channels contribute to serotonergic modulation of ventral surface chemosensitive neurons and respiratory activity.
Chemosensitive neurons in the retrotrapezoid nucleus (RTN) provide a CO2/H(+)-dependent drive to breathe and function as an integration center for the respiratory network, including serotonergic raphe neurons. We recently showed that serotonergic modulation of RTN chemoreceptors involved inhibition of KCNQ channels and activation of an unknown inward current. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels are the molecular correlate of the hyperpolarization-activated inward current (Ih) and have a high propensity for modulation by serotonin. To investigate whether HCN channels contribute to basal activity and serotonergic modulation of RTN chemoreceptors, we characterize resting activity and the effects of serotonin on RTN chemoreceptors in vitro and on respiratory activity of anesthetized rats in the presence or absence of blockers of KCNQ (XE991) and/or HCN (ZD7288, Cs(+)) channels. We found in vivo that bilateral RTN injections of ZD7288 increased respiratory activity and in vitro HCN channel blockade increased activity of RTN chemoreceptors under control conditions, but this was blunted by KCNQ channel inhibition. Furthermore, in vivo unilateral RTN injection of XE991 plus ZD7288 eliminated the serotonin response, and in vitro serotonin sensitivity was eliminated by application of XE991 and ZD7288 or SQ22536 (adenylate cyclase blocker). Serotonin-mediated activation of RTN chemoreceptors was blocked by a 5-HT7-receptor blocker and mimicked by a 5-HT7-receptor agonist. In addition, serotonin caused a depolarizing shift in the voltage-dependent activation of Ih. These results suggest that HCN channels contribute to resting chemoreceptor activity and that serotonin activates RTN chemoreceptors and breathing in part by a 5-HT7 receptor-dependent mechanism and downstream activation of Ih.


Serum chemistry templates of disease in liver, pancreas, and gallbladder.
On routine hospital admission, 23,714 patients received a 28-test serum metabolic profile. The 33 most common diseases (4,132 patients) of liver, pancreas, and gallbladder (LPG) had unique chemical templates averaging 15 significant serum deviations. Each LPG disease differed from all others by elevations of both leucine-aminopeptidase (LAP) and alkaline phosphatase (AP) levels. LAP level was low or normal and serum glutamic oxaloacetic transaminase (SGOT) and AP levels were elevated in 43 non-LPG diseases. Patients with acute and chronic pancreatitis had elevated amylase levels. The four nonmalignant diseases of the gallbladder were associated with normal levels of amylase and lactic dehydrogenase (LDH); except for silent cholelithiasis, each showed elevated total bilirubin (BIL) levels. Patients with solitary or scattered lesions of the liver had normal bilirubin levels (2,115 patients), and those with diffuse interstitial or parencymal disease had elevated BIL levels. Cancer patients had elevated LDH and alpha1 globulin (A1G) levels, but low albumin levels. The importance of comprehensive liver profiles in the treatment of psychoses is emphasized by significant liver damage in a number of these patients. A1G was normal and LDH was elevated in patients having mononucleosis, hepatitis, lupus erythematosus, alcoholism, and alcoholic cirrhosis.


Intestinal Schistosomiasis: A Rare Cause of Abdominal Pain and Weight loss.
Abdominal pain is one of the most common reasons for outpatient visits. Although intestinal schistosomiasis is extremely rare in US, it should be considered in the differential diagnosis for those patients with risk factors such as international traveling history. This case report illustrates a unique case of intestinal schistosomiasis, which presented with an eight-week history of nonspecific abdominal pain and weight loss. Her colonoscopy revealed a 10 mm polyp in the colon. Endoscopic mucosal resection confirmed the diagnosis of schistosomiasis. Treatment with Praziquantel resulted in significant improvement of her symptoms.


An efficient chromatographic system for lipoprotein fractionation using whole plasma.
We have validated a semi-automatic procedure for the efficient isolation of plasma lipoproteins from 300 microl of whole plasma (actual injection volume 200 microl) by Fast Phase Liquid Chromatography (FPLC). Modified enzymatic assays were established to allow the determination of low concentrations (1-20 mg/dl) of triglycerides and cholesterol using the Beckman CX-5 Autoanalyzer. The sum of the cholesterol contents in the fractions corresponding to low density (LDL) and high density lipoprotein (HDL) can be demonstrated to be highly correlated to values obtained with dextran sulfate/MgCl2 precipitation for HDLc (slope = 0.98, r2 = 0.997) and ultracentrifugation (beta-quant) for LDLc (slope = 1.03, r2 = 0.988). Using pure lipoprotein fractions isolated by ultracentrifugation, linear ranges of detection for HDLc and HDL apoA-I were performed at 18-95 mg/dl and 59-262 mg/dl, respectively. The ranges for LDLc were 41-435 mg/dl and 21-280 mg/dl for LDL apoB. The mean (range) fractional standard deviations for quadruplicate runs for 15 individual plasma samples ranging widely in lipoprotein concentrations were 0.97 (0.29-2.86%) for LDLc (range: 101.5-258.5 mg/dl), 3.67 (0.62-14.11%) for HDLc (range: 27.1-85.1 mg/dl) and 2.19 (0.16-6.56%) for VLDL-TG (range: 6.1-515.0 mg/dl).


[Systematic diagnosis of erythrocytosis].
Erythrocytosis is a phenomenon with life-threatening complications and a broad differential diagnosis. Erythrocytosis is usually secondary to a cardiopulmonary condition leading to a low arterial oxygen tension. A probable diagnosis can often be made on the basis of the history, physical examination, a measurement of the peripheral oxygen saturation, and simple laboratory tests. The differential diagnosis can be narrowed down by a determination of the erythropoietin concentration and the JAK2 mutation. If the erythrocytosis is found to be non-physiological, then reduction of the haematocrit via bloodletting and, depending on the diagnosis, treatment with acetylsalicylic acid are indicated.


Permease recycling and ubiquitination status reveal a particular role for Bro1 in the multivesicular body pathway.
Ubiquitination of the yeast Gap1 permease at the plasma membrane triggers its endocytosis followed by targeting to the vacuolar lumen for degradation. We previously identified Bro1 as a protein essential to this down-regulation. In this study, we show that Bro1 is essential neither to ubiquitination nor to the early steps of Gap1 endocytosis. Bro1 rather intervenes at a late step of the multivesicular body (MVB) pathway, after the core components of the endosome-associated ESCRT-III protein complex and before or in conjunction with Doa4, the ubiquitin hydrolase mediating protein deubiquitination prior to their incorporation into MVB vesicles. Bro1 markedly differs from other class E vacuolar protein sorting factors involved in MVB sorting as lack of Bro1 leads to recycling of the internalized permease back to the plasma membrane by passing through the Golgi. This recycling seems to be accompanied by deubiquitination of the permease and unexpectedly requires a normal endosome-to-vacuole transport function.


Nudix hydrolase NUDT19 regulates mitochondrial function and ATP production in murine hepatocytes.
Changes in intracellular CoA levels are known to contribute to the development of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D) in human and rodents. However, the underlying genetic basis is still poorly understood. Due to their diverse susceptibility towards metabolic diseases, mouse inbred strains have been proven to serve as powerful tools for the identification of novel genetic factors that underlie the pathophysiology of NAFLD and diabetes. Transcriptome analysis of mouse liver samples revealed the nucleoside diphosphate linked moiety X-type motif Nudt19 as novel candidate gene responsible for NAFLD and T2D development. Knockdown (KD) of Nudt19 increased mitochondrial and glycolytic ATP production rates in Hepa 1-6 cells by 41% and 10%, respectively. The enforced utilization of glutamine or fatty acids as energy substrate reduced uncoupled respiration by 41% and 47%, respectively, in non-target (NT) siRNA transfected cells. This reduction was prevented upon Nudt19 KD. Furthermore, incubation with palmitate or oleate respectively increased mitochondrial ATP production by 31% and 20%, and uncoupled respiration by 23% and 30% in Nudt19 KD cells, but not in NT cells. The enhanced fatty acid oxidation in Nudt19 KD cells was accompanied by a 1.3-fold increased abundance of Pdk4. This study is the first to describe Nudt19 as regulator of hepatic lipid metabolism and potential mediator of NAFLD and T2D development.


Phonon Screening of Excitons in Semiconductors: Halide Perovskites and Beyond.
The ab initio Bethe-Salpeter equation (BSE) approach, an established method for the study of excitons in materials, is typically solved in a limit where only static screening from electrons is captured. Here, we generalize this framework to include dynamical screening from phonons at lowest order in the electron-phonon interaction. We apply this generalized BSE approach to a series of inorganic lead halide perovskites, CsPbX_{3}, with X=Cl, Br, and I. We find that inclusion of screening from phonons significantly reduces the computed exciton binding energies of these systems. By deriving a simple expression for phonon screening effects, we reveal general trends for their importance in semiconductors and insulators, based on a hydrogenic exciton model. We demonstrate that the magnitude of the phonon screening correction in isotropic materials can be reliably predicted using four material specific parameters: the reduced effective mass, static and optical dielectric constants, and frequency of the most strongly coupled longitudinal-optical phonon mode. This framework helps to elucidate the importance of phonon screening and its relation to excitonic properties in a broad class of semiconductors.


Blink reflex discloses CNS dysfunction in neurologically asymptomatic patients with systemic sclerosis.
To investigate trigeminal-nerve, brain-stem, and brain function, in order to disclose a possible nervous system involvement in neurologically asymptomatic systemic sclerosis (SSc) patients. Using a standard electromyographic (EMG) technique, we recorded the early (R1) and late (R2) components of the blink reflex in 35 SSc patients with no history or signs of cranial-nerve impairment and 20 control subjects. SSc patients were classified as limited or diffuse SSc and also evaluated for disease duration, autoantibody pattern (ANA, ACA, Scl70) and skin score (by Rodnan modified method). Whereas no SSc patients had an abnormal R1, six (18%) had delayed R2 responses. We found no correlation between R2 latency and clinical or laboratory data. Whereas previous studies reported both R1 and R2 abnormalities (reasonably due to trigeminal neuropathy) in symptomatic SSc patients, we found selective abnormalities of the R2 components in asymptomatic patients. The selective R2 abnormality is secondary to a central dysfunction, either because of a direct impairment of the polysynaptic circuits in the medulla, or because of a decreased cortico-reticular drive on these circuits. The lack of overt trigeminal symptoms in our patients favours a suprasegmental dysfunction, possibly due to microvascular lesions disseminated in the subcortical white matter.


Correlation Between Resting Testosterone/Cortisol Ratio and Sound-Induced Vasoconstriction at Fingertip in Men.
A sound-induced sympathetic tone has been used as an index for orienting responses to auditory stimuli. The resting testosterone/cortisol ratio is a biomarker of social aggression that drives an approaching behavior in response to environmental stimuli, and a higher testosterone level and a lower cortisol level can facilitate the sympathetic response to environmental stimuli. Therefore, it is possible that the testosterone/cortisol ratio is correlated with the sound-induced sympathetic tone. The current study investigated the relationship between the resting testosterone/cortisol ratio and vasoconstriction induced by listening to sound stimuli. Twenty healthy males aged 29.0 ± 0.53 years (mean ± S.E.M) participated in the study. They came to the laboratory for 3 days and listened to one of three types of sound stimuli for 1 min on each day. Saliva samples were collected for an analysis of salivary testosterone and cortisol levels on the day of each experiment. After the collecting the saliva sample, we measured the blood volume pulse (BVP) amplitude at a fingertip. Since vasoconstriction is mediated by the activation of the sympathetic nerves, the strength of the reduction in BVP amplitude at a fingertip was called the BVP response (finger BVPR). No difference was observed between the sound-induced finger BVPR for the three types of sound stimuli (p = 0.779). The correlation coefficient between the sound-induced finger BVPR and the salivary testosterone/cortisol ratio within participants was significantly different from no correlation (p = 0.011) and there was a trend toward a significance in the correlation between the sound-induced finger BVPR and the salivary testosterone/cortisol ratio between participants (r = 0.39, p = 0.088). These results suggest that the testosterone/cortisol ratio affects the difference in the sound-evoked sympathetic response.


Prediction of multiple resonance characteristics by an extended resistor-inductor-capacitor circuit model for plasmonic metamaterials absorbers in infrared.
The resonance characteristics of plasmonic metamaterials absorbers (PMAs) are strongly dependent on geometric parameters. A resistor-inductor-capacitor (RLC) circuit model has been extended to predict the resonance wavelengths and the bandwidths of multiple magnetic polaritons modes in PMAs. For a typical metallic-dielectric-metallic structure absorber working in the infrared region, the developed model describes the correlation between the resonance characteristics and the dimensional sizes. In particular, the RLC model is suitable for not only the fundamental resonance mode, but also for the second- and third-order resonance modes. The prediction of the resonance characteristics agrees fairly well with those calculated by the finite-difference time-domain simulation and the experimental results. The developed RLC model enables the facilitation of designing multi-band PMAs for infrared radiation detectors and thermal emitters.


Aprotinin in spine surgery: review of the literature.
Based on a literature review, this article evaluates the efficacy of aprotinin to limit blood transfusion during spine surgery. Most prospective studies confirm this effect. However, broader studies are required to evaluate adverse effects. Severe complications are rarely, if ever, reported. Given the small size of most samples, complications are expected because of the widespread use of the drug. The cost of the medication has to be balanced with the cost of blood transfusion. A careful use of aprotinin allows a surgeon dealing with high-risk patients to avoid or limit the use of transfusions. For patients who are not high-risk, aprotinin should be avoided until other questions are answered.


Efficacy, Safety and Tolerability of Augmentative rTMS in Treatment of Major Depressive Disorder (MDD): A Prospective Cohort Study in Croatia.
An increasing body of research suggest that repetitive Transcranial Magnetic Stimulation (rTMS) is effective and safe treatment option for patients with major depressive disorder (MDD). The Psychiatric Hospital "Sveti Ivan" has the first TMS laboratory with rTMS and deep TMS (dTMS) in Croatia. The objective of this study was to assess the efficacy, safety and tolerability of augmentative rTMS treatment vs standard treatment in Croatian patients with major depressive disorder (MDD). Total of 93 MDD patients were enrolled; 41 of them were treated by augmentative rTMS and 52 were treated by standard (psychopharmacotherapy and psychotherapy) therapy only. We delivered rTMS to the left dorsolateral prefrontal cortex at 120% motor threshold (10 Hz, 4-second train duration), 3000 pulses per session using a figure-eight coil, minimum of 20 sessions during four weeks. Our key outcome was the change in Hamilton Depression Scale (HAM-D17) result from baseline to 4th week. Our secondary outcomes were changes in Hamilton Anxiety (HAM-A) and WHOQOL-BREF scales. After four weeks the changes of HAM-D17 and HAM-A results were significantly different between the group of patients treated by augmentative rTMS (48% and 53% decrease, respectively) and the group of patients treated by the standard therapy alone (24% and 30% decrease) (P=0.004, P=0.007). Absolute benefit increase defined as the difference between rates of remission (HAM-D17 ≤7) in rTMS and control group was 33% (P=0.001). Number of patients needed to treat with rTMS in order to achieve remission in one patient was NNT=3. In a group of patients treated with augmentative rTMS 21/41 (51%), and in control group 17/52 (33%) were responders (P=0.071). It seems that augmentative treatment with rTMS is more effective on depression and anxiety symptoms than standard therapy in MDD with equal safety and tolerability. Randomized, controlled studies are required to verify this finding.


Personality traits in substance use disorders and obesity when compared to healthy controls.
Although personality traits are implicated in substance use disorders (SUDs) and obesity, differences and similarities between them have not been assessed. Our main aim was to compare personality traits between people with different SUDs, obese people and healthy controls. This was a secondary analysis of personality scores obtained from participants in neuroimaging studies from Brookhaven National Laboratory and the Laboratory of Neuroimaging, National Institutes of Health. United States. Individuals with obesity (OB) n = 41, alcohol use disorder (AUD) n = 39, marijuana use disorder (MUD) n = 24, cocaine use disorder (CUD) n = 100, and healthy controls (HC) n = 117 (237 males and 84 females). The Multidimensional Personality Questionnaire, which characterizes positive emotionality (PEM), negative emotionality (NEM) and constraint (CON) traits. Adjusted covariates included cigarette smoking status, age, gender and body mass index (BMI). Multivariate analysis of covariance showed a main group effect (i.e. OB, AUD, MUD, CUD and HC) only on NEM (P < 0.0001, η2 = 0.17) and CON (P = 0.005, η2 = 0.12). Specifically, NEM was higher in AUD (P < 0.0001, d = 10.4), CUD (P < 0.0001, d = 8.2) and MUD (P = 0.001, d = 9.2), but not in OB (P > 0.05, d = 2.8) relative to HC. CUD showed lower CON (P = 0.015, d = 5.4) and PEM (P = 0.018, d = 4.8) than HC; however, these differences were not significant in the other groups. NEM and CON were negatively correlated for groups combined (r = -0.26, P < 0.0001), and separately for OB (r = -0.49, P = 0.001) and CUD (r = -0.22, P = 0.03). Cigarette smoking status did not influence group differences in NEM, PEM or CON. Compared with healthy controls, people with substance use disorders appear to show higher negative emotionality, and people with cocaine use disorders appear to show lower positive emotionality and constraint traits. Similar findings were not found among people with obesity.


Viruses in case series of tumors: Consistent presence in different cancers in the same subject.
Studies investigating presence of viruses in cancer often analyze case series of cancers, resulting in detection of many viruses that are not etiologically linked to the tumors where they are found. The incidence of virus-associated cancers is greatly increased in immunocompromised individuals. Non-melanoma skin cancer (NMSC) is also greatly increased and a variety of viruses have been detected in NMSC. As immunosuppressed patients often develop multiple independent NMSCs, we reasoned that viruses consistently present in independent tumors might be more likely to be involved in tumorigenesis. We sequenced 8 different NMSCs from 1 patient in comparison to 8 different NMSCs from 8 different patients. Among the latter, 12 different virus sequences were detected, but none in more than 1 tumor each. In contrast, the patient with multiple NMSCs had human papillomavirus type 15 and type 38 present in 6 out of 8 NMSCs.


Asymmetric tandem 1,5-hydride shift/ring closure for the synthesis of chiral spirooxindole tetrahydroquinolines.
The direct functionalization of sp(3) C-H bonds through a tandem 1,5-hydride shift/ring closure is described. Various optically active spirooxindole tetrahydroquinoline derivatives bearing contiguous quaternary or tertiary stereogenic carbon centers were readily synthesized. A chiral scandium complex of N,N'-dioxide promoted the reactions in good yields (up to 97%) with excellent diastereoselectivities (>20:1) and enantioselectivities (up to 94% ee). Kinetic isotope effect (KIE) experiments and internal redox reactions of chiral substrates were conducted, and the results provided intriguing information that helped clarify the mechanism of the reaction.


Penetrating ballistic-like brain injury in the rat: differential time courses of hemorrhage, cell death, inflammation, and remote degeneration.
Acute and delayed cerebral injury was assessed in a recently developed rat model of a penetrating ballistic-like brain injury (PBBI). A unilateral right frontal PBBI trajectory was used to induce survivable injuries to the frontal cortex and striatum. Three distinct phases of injury progression were observed. Phase I (primary injury, 0-6 h) began with immediate (<5 min) intracerebral hemorrhage (ICH) that reached maximal volumetric size at 6 h (27.0 +/- 2.9 mm(3)). During Phase II (secondary injury, 6-72 h), a core lesion of degenerate neurons surrounding the injury track expanded into peri-lesional areas to reach a maximal volume of 69.9 +/- 6.1 mm(3) at 24 h. The core lesion consisted of predominately necrotic cell death and included marked infiltration of both neutrophils (24 h) and macrophages (72 h). Phase III (delayed degeneration, 3-7 days) involved the degeneration of neurons and fiber tracts remote from the core lesion including the thalamus, internal capsule, external capsule, and cerebral peduncle. Overall, different time courses of hemorrhage, lesion evolution, and inflammation were consistent with complementary roles in injury development and repair, providing key information about these mediators of primary, secondary, and delayed brain injury development. The similarities/differences of PBBI to other focal brain injury models are discussed.


Nicotine-Free e-Cigarette Vapor Exposure Stimulates IL6 and Mucin Production in Human Primary Small Airway Epithelial Cells.
Electronic cigarettes (e-cigs) are relatively new devices that allow the user to inhale a heated and aerosolized solution. At present, little is known about their health effects in the human lung, particularly in the small airways (<2 mm in diameter), a key site of airway obstruction and destruction in chronic obstructive pulmonary disease and other acute and chronic lung conditions. The aim of this study was to investigate the effect of e-cigarettes on human distal airway inflammation and remodeling. We isolated primary small airway epithelial cells from donor lungs without known lung disease. Small airway epithelial cells were cultured at air-liquid interface and exposed to 15 puffs vapor obtained by heating a commercially available e-cigarette solution (e-vapor) with or without nicotine. After 24 hrs of e-vapor exposure, basolateral and apical media as well as cell lysates were collected to measure the pleiotropic cytokine interleukin 6 (IL6) and MUC5AC, one of the major components in mucus. Unlike the nicotine-containing e-vapor, nicotine-free e-vapor significantly increased the amount of IL6, which was coupled with increased levels of intracellular MUC5AC protein. Importantly, a neutralizing IL6 antibody (vs an IgG isotype control) significantly inhibited the production of MUC5AC induced by nicotine-free e-vapor. Our results suggest that human small airway epithelial cells exposed to nicotine-free e-vapor increase the inflammatory response and mucin production, which may contribute to distal lung airflow limitation and airway obstruction.


Diabetes, infection risk and COVID-19.
Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial, and fungal infections. The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries and claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19. In this review, I summarize the clinical data on the risk for infectious diseases in individuals with diabetes while highlighting the mechanisms for altered immune regulation. The focus is on coronaviruses. Based on the new clinical data obtained from COVID-19 patients, a discussion of mechanisms, such as cytokine storm, pulmonary and endothelial dysfunction, and hypercoagulation, that may render individuals with diabetes more vulnerable to COVID-19 is provided. Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and the pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to designing tailored treatments and clinical management of individuals affected by diabetes.


Laparoscopic cholecystectomy under spinal-epidural anesthesia vs. general anaesthesia: a prospective randomised study.
Laparoscopic cholecystectomy (LC) is usually performed under the general anesthesia (GA). Aim of the study is to investigate the availability, safety and side effects of combined spinal/epidural anesthesia (CSEA) and comparison it with GA for LC. Forty-nine patients who have a LC plan were included into the study. The patients were randomly divided into GA (n = 25) and CSEA (n = 24) groups. Intraoperative and postoperative adverse events, postoperative pain levels were compared between groups. Anesthesia procedures and surgeries for all patients were successfully completed. After the organization of pneumoperitoneum in CSEA group, 3 patients suffered from shoulder pain (12.5%) and 4 patients suffered from abdominal discomfort (16.6%). All these complaints were recovered with IV fentanyl administration. Only 1 patient developed hypotension which is recovered with fluid replacement and no need to use vasopressor treatment. Postoperative shoulder pain was significantly less observed in CSEA group (25% vs. 60%). Incidence of postoperative nausea and vomiting (PONV) was less observed in CSEA group but not statistically significant (4.2% vs. 20%). In the group of CSEA, 3 patients suffered from urinary retention (12.5%) and 2 patients suffered from spinal headache (8.3%). All postoperative pain parameters except 6th hour, were less observed in CSEA group, less VAS scores and less need to analgesic treatment in CSEA group comparing with GA group. CSEA can be used safely for laparoscopic cholecystectomies. Less postoperative surgical field pain, shoulder pain and PONV are the advantages of CSEA compared to GA.


Soluble thrombomodulin, plasma-derived unactivated protein C, and recombinant human activated protein C in sepsis.
To review the physiologic and biochemical mechanisms and the rationale for the use of soluble thrombomodulin, plasma-derived protein C, and recombinant human activated protein C in sepsis. Research and review articles related to the protein C pathway published in English from 1960 to present. The protein C anticoagulant pathway plays a major role in controlling microvascular coagulation and inflammation. Protein C is the zymogen of the vitamin K-dependent serine protease activated protein C. Protein C is converted to activated protein C when thrombin complexes with thrombomodulin, an endothelial surface transmembrane glycoprotein. Activated protein C inactivates factors Va and VIIIa and effectively limits further thrombin generation. This protein also enhances endogenous fibrinolytic activity and modulates the inflammatory response. A rapid depletion of protein C occurs in sepsis, which contributes to sepsis-induced coagulopathy and correlates with a poor prognosis. The decrease in tissue levels of thrombomodulin in patients with meningococcemia suggests that the ability to convert protein C to activated protein C may also be compromised. The ability of soluble thrombomodulin to block fibrinogen clotting and cell activation, to activate protein C, and to promote thrombin inhibition in different animal models suggests that soluble thrombomodulin could be a useful therapeutic agent in sepsis. However, soluble thrombomodulin is less effective in blocking fibrinogen and platelet activation and in promoting thrombin inhibition than endothelial surface membrane-bound thrombomodulin. Only activated protein C, and not protein C, has clearly shown a reduction in mortality in experimental animal models of sepsis and in humans. The multipotent pharmacodynamic effects (antithrombotic, profibrinolytic, and anti-inflammatory) of activated protein C may explain why recombinantly derived human activated protein C is the first experimental agent to demonstrate a significant survival benefit in patients with severe sepsis.


Some considerations for optimization of desorption chromatography.
The effect of isotherm parameters of a displacer on the efficiency of desorption Chromatography has been investigated numerically. A general nonlinear multicomponent rate equation model with Langmuir isotherm was used in this study. It was found that the best displacer in this kind of operation is usually not the one that is more strongly adsorbed than the adsorbates when the operation is to displace and concentrate the adsorbates from a saturated or partially saturated column and to minimize the amount of displacer used. The desorption Chromatography is different from the classical displacement development in both operational purpose and the requirement for the displacer. The desorption Chromatography in industrial practice was also analyzed and discussed for the case in which the displacer is introduced in either the same or the reverse flow direction after an incomplete frontal adsorption operation.


Unloading, ablation, bridging and transplant: different indications and treatments using the Impella 5.5 as longer-term circulatory support in one patient-an interdisciplinary case report.
In patients with cardiogenic shock the clinical treatment often involves temporary mechanical circulatory support for initial haemodynamic stabilization to enable further assessment of therapeutic strategies. The surgically implanted Impella 5.5 can be used for several indications like ventricular unloading, haemodynamic support during high-risk interventions, and as a bridge-to-transplant strategy.We present an interdisciplinary managed case of using Impella 5.5 for multiple indications and treatment strategies in one patient. A 66-year-old patient with known dilated cardiomyopathy was admitted with non-ST-elevation myocardial infarction and underwent urgent coronary bypass grafting. His native heart function did not recover and he experienced recurrent episodes of sustained ventricular tachycardia (VT) and electrical storm. He was evaluated for heart transplantation (OHT) and received a VT-ablation. However, he suffered an in-hospital cardiac arrest (IHCA) with subsequent implantation of an extracorporeal life support system (ECLS). After surgical placement of an Impella 5.5 due to left ventricular distension and pulmonary congestion, the ECLS was successfully weaned. He showed good neurological outcomes and underwent another high-risk VT-ablation. The patient was further stabilized under Impella 5.5 support in a bridge-to-transplant strategy. After 34 days he underwent a successful OHT. In this interdisciplinary case report the surgically implanted Impella 5.5 as temporary mechanical circulatory support was used for multiple different indications and treatment strategies like ventricular unloading, haemodynamic support during high-risk interventions, and as bridge-to-transplant strategy in one patient.


Evaluating Protection Against Infectious Bronchitis Virus by Clinical Signs, Ciliostasis, Challenge Virus Detection, and Histopathology.
In this study, we examined the association among clinical signs, ciliostasis, virus detection, and histopathology for evaluating protection of vaccinated chickens against homologous and heterologous infectious bronchitis virus (IBV) challenge. At 5 days following challenge with IBV, we found a good correlation among clinical signs, ciliostasis in the trachea, challenge virus detection, and microscopic lesions in the trachea, with all four criteria being negative in fully protected birds and positive in fully susceptible birds. In partially protected birds we observed clinical signs and detected challenge virus; however, the ciliated epithelium was intact. In a second experiment, we challenged fully protected, partially protected, and fully susceptible birds with IBV, and then at 5 days postchallenge we gave the birds an opportunistic bacterium intranasally. Twenty Bordetella avium colonies were recovered from one of five fully protected birds, and only five colonies were isolated from two of five partially protected birds without ciliostasis, whereas in birds with ciliostasis, numerous colonies were isolated. Obviously, decreasing IBV infection and replication in the upper respiratory tract will decrease transmission and mutations, leading to variant viruses, and herein we demonstrate that protection of the cilia will decrease secondary bacterial infections, which have been shown to lead to condemnations and increased mortality. Thus, it appears that examining both criteria would be important when evaluating IBV vaccine efficacy.


Positron emission tomography and computed tomography angiography for the diagnosis of giant cell arteritis: A real-life prospective study.
The use of 18F-fluoro-deoxyglucose positron emission tomography scan (FDG-PET) and computed tomography angiography (CTA) to improve accuracy of diagnosis of giant cell arteritis (GCA) is a very important clinical need. We aimed to compare the diagnostic performance of FDG-PET and CTA in patients with GCA.FDG-PET and CTA were acquired in all consecutive patients suspected for GCA. Results of FDG-PET and CTA were compared with the final diagnosis based on clinical judgment, temporal artery biopsy (TAB) findings, and ACR criteria. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for each method.Twenty-four patients suspected for GCA were included. Fifteen (62.5%) were ultimately diagnosed as having GCA. Among them, all fulfilled ACR criteria and 6 had biopsy-proven GCA. Strong FDG uptake in large vessels was found in 10 patients who all had GCA. Mean maximal standard uptake values (SUVmax) per patient measured at all the arterial territories were of 3.7 (range: 2.8-4.7). FDG uptake was negative in 14 patients including 9 and 5 patients without and with GCA, respectively. Mural thickening suggestive of aortitis or branch vessel arteritis was observed on CTA in 11 patients with and 2 patients without GCA. No mural thickening was observed in 11 patients including 7 patients without and 4 patients with GCA. Overall, sensitivity was 66.7% and 73.3%, specificity was 100% and 84.6%, NPV was 64.3% and 64.6%, and PPV was 100% and 84.6% of FDG-PET and CTA, respectively.Both FDG-PET and CTA have a strong diagnostic yield for the diagnosis of GCA. FDG-PET appeared to have a higher PPV as compared to CTA and may be the preferred noninvasive technique to explore patients with suspected GCA.


The Dutch Central Sensitization Inventory (CSI): Factor Analysis, Discriminative Power, and Test-Retest Reliability.
A standardized assessment of central sensitization can be performed with the Central Sensitization Inventory (CSI), an English questionnaire consisting of 25 items relating to current health symptoms. The aim of this study was to translate the CSI into Dutch, to perform a factor analysis to reveal the underlying structure, examine its discriminative power, and test-retest reliability. The CSI was first translated into Dutch. A factor analysis was conducted on CSI data of a large group of chronic pain patients (n=368). The ability to discriminate between chronic pain patients (n=188) and pain-free controls (n=49) was determined and the test-retest reliability for chronic pain patients (n=36) and controls (n=45) with a time interval of 3 weeks was evaluated. The exploratory factor analysis resulted in a 4-factor model based on 20 items, representing the domains "General disability and physical symptoms" (Cronbach α=0.80), "Higher central sensitivity"(Cronbach α=0.78), "Urological and dermatological symptoms"(Cronbach α=0.60), and "Emotional distress"(Cronbach α=0.80). Furthermore, a parsimonious second-order factor model was found, where the factor "General central sensitization" was underlying the 4 first-order factors. Chronic pain patients scored significantly worse on all 4 factors. The test-retest reliability was excellent values in both chronic pain patients (ICC=0.88) and controls (ICC=0.91). The original CSI was translated into Dutch and did not reveal any problems during data acquisition. The domains represented by the 4 factors may be useful in setting up specific patient profiles and treatment targets. To conclude, the Dutch CSI revealed 4 distinguishable domains, showed good internal consistency for the total score and 3 out of 4 domains, good discriminative power, and excellent test-retest reliability.


Leukocyte adhesion molecules: potential targets for therapeutic intervention in kidney diseases.
Neutrophils and monocytes (phagocytes) are important mediators of injury in many inflammatory diseases, including glomerulonephritis and vasculitis. Current treatment modalities (eg, corticosteroids, cytotoxic agents) are relatively nonspecific in their actions, frequently ineffective, and often associated with immunologic or metabolic complications. Recent advances in cellular and molecular immunobiology have suggested novel targets for therapeutic intervention. Phagocyte adhesion to endothelial cells, in particular, is a central event in the recruitment of phagocytes to sites of inflammation. Phagocyte trafficking to the extravascular space requires the coordinated interactions of several families of adhesion molecules, including the selectins, integrins, and immunoglobulin-like molecules. Initial attachment appears to be achieved by the interaction of phagocyte or endothelial cell selectins with carbohydrate-containing counter-receptors. These events facilitate immobilization of phagocytes via the interaction of phagocyte integrins with immunoglobulin-like molecules on endothelial cells and diapedesis to the extravascular tissue. Chemoattractants and cytokines regulate adhesion by altering the avidity or surface expression of preformed molecules and by influencing de novo synthesis of adhesion molecules. The intensity and composition of leukocyte infiltrates at sites of inflammation likely reflect the local balance of pro- and anti-inflammatory chemoattractants and cytokines and the profile of adhesion molecules on invading and resident cells. Adhesion may also promote tissue injury by augmenting phagocyte oxidative bursts and lysosomal enzyme release and by facilitating release of these cytotoxic molecules in close proximity to tissue cells. In addition, adhesion may amplify the levels and types of inflammatory mediators within a local milieu by promoting transcellular eicosanoid biosynthesis during cell-cell interaction. Increased adhesion molecule expression has been reported in glomerulonephritis, vasculitis, tubulointerstitial nephritis, transplant rejection, and hemodialysis "first-use" reactions. In addition, leukocyte adhesion may be an important event in the pathophysiology of ischemia-reperfusion injury. Monoclonal antibodies against adhesion molecules confer dramatic protection in several models of renal inflammation. Further studies in this area may yield potent and specific therapies for common renal diseases.


The Evolutionary Basis of Translational Accuracy in Plants.
Mistranslation errors compromise fitness by wasting resources on nonfunctional proteins. In order to reduce the cost of mistranslations, natural selection chooses the most accurately translated codons at sites that are particularly important for protein structure and function. We investigated the determinants underlying selection for translational accuracy in several species of plants belonging to three clades: Brassicaceae, Fabidae, and Poaceae. Although signatures of translational selection were found in genes from a wide range of species, the underlying factors varied in nature and intensity. Indeed, the degree of synonymous codon bias at evolutionarily conserved sites varied among plant clades while remaining uniform within each clade. This is unlikely to solely reflect the diversity of tRNA pools because there is little correlation between synonymous codon bias and tRNA abundance, so other factors must affect codon choice and translational accuracy in plant genes. Accordingly, synonymous codon choice at a given site was affected not only by the selection pressure at that site, but also its participation in protein domains or mRNA secondary structures. Although these effects were detected in all the species we analyzed, their impact on translation accuracy was distinct in evolutionarily distant plant clades. The domain effect was found to enhance translational accuracy in dicot and monocot genes with a high GC content, but to oppose the selection of more accurate codons in monocot genes with a low GC content.


Aeroacoustics measurement of the gas leakage rate for single hole.
Gas sealing structures have been widely used in various engineering fields, and the gas leakage rate is one of the most important indicators for evaluating the sealing performance of sealing structures. In this paper, an aeroacoustic measurement method is proposed to measure the gas leakage rate by using one sound pressure sensor based on known location of a single leakage hole combining the aeroacoustic theory with numerical simulation results. First, the basic measurement principle is established using the Lighthill acoustic analogy method. Then, the finite element method is used to calculate the fitting parameters in leakage rate equations. Finally, the single-hole leakage experiments are carried out to verify the effectiveness of this gas leakage rate measurement method. The measurement results are in good agreement with the results recorded by flowmeters.


Centrally administered neuropeptide S activates orexin-containing neurons in the hypothalamus and stimulates feeding in rats.
Neuropeptide S (NPS) is a newly identified transmitter that modulates arousal and anxiety. To determine potential neuronal targets for NPS, we studied the pattern of neuronal activation as indicated by the expression of Fos. Centrally administered NPS increased Fos-like immunoreactivity (FLI) in the paraventricular, dorsomedial nuclei and lateral hypothalamic area (LHA) of the hypothalamus, the midline thalamic nuclei, and the amygdala, many parts of which are involved in the regulation of emotion, arousal, and feeding. In particular, we noted that Fos-immunoreactive (Fos-ir) levels were increased in orexin-expressing neurons in the LHA. We then studied whether an icv injection of NPS increased food intake. The injection of NPS (1 nmol) significantly stimulated feeding at 2 h in rats, but there was no difference in food intake at 4 h or 24 h. These results suggest that arousal and feeding induced by NPS in the central nervous system may be related to the activation of orexin-expressing neurons.


Adsorption of several metal ions onto a low-cost biosorbent: kinetic and equilibrium studies.
Sugar beet pulp generated by sugar-refining factories has been shown to be an effective adsorbent for the removal of heavy metals from aqueous solutions. The structural components related to the metallic adsorption being determined, batch adsorption studies were performed for several metal ions, namely, Pb2+, Cu2+, Zn2+, Cd2+, and Ni2+ cations. Two simple kinetic models, that is, pseudo-first- and pseudo-second-order, were tested to investigate the adsorption mechanisms. The kinetic parameters of the models were calculated and discussed. For an 8 x 10(-4) M initial metal concentration, the initial sorption rates (v0) ranged from 0.063 mmol x g(-1) x min(-1) for Pb2+ to 0.275 mmol x g(-1) x min(-1) for Ni2+ ions, in the order Ni2+ > Cd2+ > Zn2+ > Cu2+ > Pb2+. The equilibrium data fitted well with the Langmuir and Freundlich models and showed the following affinity order of the material: Pb2+ > Cu2+ > Zn2+ > Cd2+ > Ni2+. The metal removal was strongly dependent on pH and, to a lesser extent, ionic strength. Ion exchange with Ca2+ ions neutralizing the carboxyl groups of the polysaccharide was found to be the predominant mechanism, added with complexation for Pb2+, Cu2+, and Zn2+ metals.


Cox-2 inhibitors: today and tomorrow.
The elucidation of inducible cyclooxygenase (Cox-2) dependent inflammatory pathways led to the development of specific Cox-2 inhibitors, the coxibs. These agents include the currently available celecoxib and rofecoxib and such second-generation agents as parecoxib, valdecoxib, and etoricoxib. The therapeutic advantage of coxibs is founded primarily in their lack of significant gastrointestinal (GI) side effects. Clinical trials have demonstrated the efficacy of coxibs to be completely comparable with traditional nonsteroidal anti-inflammatory drugs (NSAIDs), and pharmacoeconomics suggest favorable cost/benefit ratios with these agents compared with traditional NSAIDs, related to their reduced GI complication profiles and lower indirect costs associated with disability. Although several clinical questions remain (eg, use with low-dose aspirin, risk of thrombosis, myocardial infarction, edema, and hypertension), the emergence and clinical utility of coxibs is likely to continue on the basis of their efficacy and relative GI safety advantage. Although newer, more specific Cox-2 inhibitors may alter the choice, it is likely that this class of anti-inflammatories will become (if they have not already) the drugs of first choice in the treatment of acute pain, chronic pain, and most rheumatic conditions in the 21st century. In addition to the treatment of rheumatic conditions, it is possible that coxibs will also be of clinical utility in protection against malignant transformation and Alzheimer disease.


Deliberate self-harm and suicide: a review from Pakistan.
Suicide is now considered a major public health problem, especially in low income countries. A systematic review was conducted to identify risk factors and causes of deliberate self-harm and suicide in Pakistan - a Muslim, South Asian nation. In addition, the role of emergency department-based surveillance is explored. Four electronic databases (PubMed, CINAHL Plus, MDConsult, PakMediNet) were searched and 23 studies were reviewed. Risk factors for deliberate self-harm included young age (less than 35 years), being female, occupation (housewives), being married and low socio-economic status; while reported risk factors for suicide were young age (less than 35 years), male gender, being married and low socio-economic status. Medications were commonly used for deliberate self-harm while firearm, hanging and organophosphorus poisoning were more frequent means for suicide. The most common reported cause for both health outcomes was interpersonal conflict. There is accumulating evidence that deliberate self-harm and suicide have increased in recent years in Pakistan. There is a need for greater attention and in-depth studies to elaborate on causative mechanisms for these public health issues.


[Prophylactic effect of tropisetron hydrochloride against nausea and vomiting in patients receiving chemotherapy for hematological malignancies].
To establish the effectiveness of oral 5-HT(3) antagonist, oral 5 mg tropisetron was introduced in the 21 cases with hematological malignancies for the prevention of chemotherapy-induced nausea and vomiting. Nausea and vomiting did not develop in 81% of patients receiving the tropisetron in this study. The results suggested that oral tropisetron is effective for the control of acute, and to a lesser extent, delayed, nausea and vomiting. The drug enhanced patients' quality of life and reduced the clinical cost. In conclusion, tropisetron is effective for the prevention of chemotherapy-induced nausea and vomiting in treatment for hematological malignancies. It is suitable as first-line therapy for outpatients.


Laser cooling in solids: advances and prospects.
This review discusses the progress and ongoing efforts in optical refrigeration. Optical refrigeration is a process in which phonons are removed from a solid by anti-Stokes fluorescence. The review first summarizes the history of optical refrigeration, noting the success in cooling rare-earth-doped solids to cryogenic temperatures. It then examines in detail a four-level model of rare-earth-based optical refrigeration. This model elucidates the essential roles that the various material parameters, such as the spacing of the energy levels and the radiative quantum efficiency, play in the process of optical refrigeration. The review then describes the experimental techniques for cryogenic optical refrigeration of rare-earth-doped solids employing non-resonant and resonant optical cavities. It then examines the work on laser cooling of semiconductors, emphasizing the differences between optical refrigeration of semiconductors and rare-earth-doped solids and the new challenges and advantages of semiconductors. It then describes the significant experimental results including the observed optical refrigeration of CdS nanostructures. The review concludes by discussing the engineering challenges to the development of practical optical refrigerators, and the potential advantages and uses of these refrigerators.


National Patterns in Utilization of Knee and Hip Arthroscopy: An Analysis of Racial, Ethnic, and Geographic Disparities in the United States.
Racial and ethnic disparities in the field of orthopaedic surgery have been reported extensively across many subspecialties. However, these data remain relatively sparse in orthopaedic sports medicine, especially with respect to commonly performed procedures including knee and hip arthroscopy. To assess (1) differences in utilization of knee and hip arthroscopy between White, Black, Hispanic, and Asian or Pacific Islander patients in the United States (US) and (2) how these differences vary by geographical region. Descriptive epidemiology study. The study sample was acquired from the 2019 National Ambulatory Surgery Sample database. Racial and ethnic differences in age-standardized utilization rates of hip and knee arthroscopy were calculated using survey weights and population estimates from US census data. Poisson regression was used to model age-standardized utilization rates for hip and knee arthroscopy while controlling for several demographic and clinical variables. During the study period, rates of knee arthroscopy utilization among White patients were significantly higher than those of Black, Hispanic, and Asian or Pacific Islander patients (ie, per 100,000, White: 180.5, Black: 113.2, Hispanic: 122.2, and Asian: 58.6). Disparities were even more pronounced among patients undergoing hip arthroscopy, with White patients receiving the procedure at almost 4 to 5 times higher rates (ie, per 100,000, White: 12.6, Black: 3.2, Hispanic: 2.3, Asian or Pacific Islander: 1.8). Disparities in knee and hip arthroscopy utilization between White and non-White patients varied significantly by region, with gaps in knee arthroscopy being most pronounced in the Midwest (adjusted rate ratio, 2.0 [95% CI, 1.9-2.1]) and those in hip arthroscopy being greatest in the West (adjusted rate ratio, 5.3 [95% CI, 4.9-5.6]). Racial and ethnic disparities in the use of knee and hip arthroscopy were found across the US, with decreased rates among Black, Hispanic, and Asian or Pacific Islander patients compared with White patients. Disparities were most pronounced in the Midwest and South and greater for hip than knee arthroscopy, possibly demonstrating emerging inequality in a rapidly growing and evolving procedure across the country.


Diiodido{2-(morpholin-4-yl)-N-[1-(2-pyrid-yl)ethyl-idene]ethanamine-κN,N',N''}zinc.
In the title compound, [ZnI(2)(C(13)H(19)N(3)O)], the Zn(II) ion is five-coordinated in a distorted square-pyramidal geometry, in which the basal plane is defined by three N atoms from the Schiff base ligand and one iodide ion. A second iodide ligand, situated in the apical position, completes the coordination geometry. In the crystal structure, C-H⋯O hydrogen bonds link a pair of mol-ecules around an inversion centre into a dimer.


[Impact of allergic airway diseases on risk of attention deficit hyperactivity disorder in school-age children].
Objective: To investigate the impact of allergic airway diseases on the risk of attention deficit hyperactivity disorder (ADHD) in school-age children. Method: Used stratified cluster sampling method, school-age children in first to sixth grade in primary schools in 9 randomly selected cities including Shanghai, Guangzhou, Xi'an, and Wuhan were enrolled in the study. Interview of parents with questionnaires, which included school-age individual and family social environment questionnaire (including history of diagnosed ADHD, allergic rhinitis, and bronchial asthma) and Children's Sleep Habits Questionnaire (CSHQ), were finished and collected during November to December in 2005.Diagnosed allergic rhinitis and asthma by specialist were independent variables and divided into following three categories as no allergic diseases (neither allergic rhinitis nor asthma), single allergic disease (allergic rhinitis or asthma), and combined allergic diseases (allergic rhinitis and asthma). Diagnosed ADHD as dependent variable, binary logistic regress model was used to analyze the risks of ADHD in school-age children. Result: Totally 23 791 questionnaires were handed out, while 22 018 were collected. The children had an average age of (8.8±1.8) years, within which 10 869 were male, and 11 021 were female. The risk ratios of ADHD were 2.197 (95%CI: 1.823-2.648) and 3.150 (95%CI: 2.082-4.760) in children with single allergic disease and combined allergic diseases separately. There was no significant difference after adjusting for the factor of sleep habits, as the risk ratios were 2.055 (95%CI: 1.683-2.508) and 3.140 (95%CI: 2.061-4.784) in children with single and combined allergic airway disease separately. Conclusion: Allergic rhinitis and bronchial asthma increased the risk of ADHD, not depending on sleep habits. Hence, allergic airway diseases could be independent risk factors of ADHD.


Sucrase-isomaltase: a marker associated with the progression of adenomatous polyps to adenocarcinomas.
Adenocarcinomas of the colon arise from adenomatous polyps. We hypothesized that sucrase-isomaltase (SI), a glycoprotein hydrolase, found in normal small intestine, fetal colon, and colon carcinomas is a marker associated with progression of adenomatous polyps with dysplasia to adenocarcinomas. To examine this hypothesis, we performed immunostaining using a polyclonal antihuman SI antibody in 32 adenomatous polyps with varying degrees of dysplasia. In addition, sucrase enzyme activity was determined in three sets of simultaneously harvested polyps, cancer, and adjacent normal mucosa from the same patient. All severely dysplastic polyps (6/6) exhibited SI staining. Most polyps (85%) with 3+ staining (i.e., greater than 10% of polyp positive for SI) had severe dysplasia, whereas those with mild dysplasia had either 1% to 5% staining or no staining in 95% of the cases. These data indicate that the extent of SI immunostaining in polyps correlates with the degree of dysplasia (p = 0.0001). Sucrase-isomaltase activity in the polyps was 18.1 +/- 1.8 mU/mg (mean +/- SD); in adjacent carcinoma SI activity was 29.1 +/- 1.8 mU/mg. Adjacent mucosa showed no activity in all cases. In summary, our results suggest that SI expression correlates with the progression of dysplastic adenomatous polyps to carcinoma. Sucrase-isomaltase expression may be useful as a clinical marker to improve our prognostic capabilities in patients with dysplastic lesions of the colon, that is, inflammatory bowel disease.


Spacer-arm modulated gene delivery efficacy of novel cationic glycolipids: design, synthesis, and in vitro transfection biology.
Design, syntheses and relative in vitro gene delivery efficacies of six novel cationic glycolipids 1-6 containing open-form galactosyl units in CHO, COS-1, MCF-7 and A549 cells are described. The results of the present structure-activity investigation convincingly demonstrate that the in vitro gene delivery efficacies of galactosylated cationic glycolipids are strikingly dependent on the absence of a spacer-arm between the open-form galactose and the positively charged nitrogen atom in their headgroup region. While the cationic glycolipids 1-3 with no headgroup spacer unit between the positively charged nitrogen and galactose showed high in vitro gene transfer efficacies in all four cells (lipids 1 and 2 with myristyl and palmityl tails, respectively, being the most efficacious), lipids 4-6 with five-carbon spacer units between the quaternized nitrogen and galactose heads were essentially transfection incompetent. The transfection inhibiting role of the five-carbon spacer unit in the headgroup region of the present novel class of cationic lipids was demonstrated by both beta-galactosidase reporter gene expression and histochemical X-gal staining assays. Results of MTT assay-based cell viability measurements in representative MCF7 cells show that cell viabilities of lipoplexes (lipid:DNA complexes) prepared from all the lipids 1-6 are remarkably high. Thus, possibilities of differential cellular cytotoxicities playing any key role behind the strikingly contrasting transfection properties of lipids 1-3 with no spacer and lipids 4-6 with a spacer unit in the headgroup regions was ruled out. Electrophoresis gel patterns in DNase I sensitivity assays are consistent with more free DNA (accessible to DNase I) being present in lipoplexes of lipids 4-6 than in lipoplexes of lipids 1-3. Thus, the results of our DNase I protection experiments support the notion that enhanced degradation of DNA associated with lipoplexes of lipids 4-6 may play an important role in abolishing their in vitro gene transfer efficacies.


Interferon beta results in immediate reduction of contrast-enhanced MRI lesions in multiple sclerosis patients followed by weekly MRI.
Interferon beta-1a and -1b reduce the frequency and severity of clinical exacerbations, and reduce both T2-weighted and contrast-enhanced MRI activity in patients with multiple sclerosis (MS). Several recent reports suggest that at the initiation of treatment there may be transient worsening of symptoms associated with the induction of interferon gamma-secreting cells. We studied eight MS patients with weekly brain MRI's after starting interferon beta treatment, and found immediate reduction in the number of contrast-enhancing lesions. Several patients did experience recurrence of previous symptoms without concomitant opening of the blood brain barrier on contrast-enhanced MRI. These data suggest that the symptoms described after the initiation of interferon beta are not associated with new disease activity, but rather may be related to preexisting lesions. This has implications for both understanding the immunopathogenesis of the disease and for its treatment.


Introducing natural thermoplastic shellac to microfluidics: A green fabrication method for point-of-care devices.
We present a sustainable fabrication method for cheap point-of-care microfluidic systems, employing hot embossing of natural shellac as a key feature of an energy-efficient fabrication method that exclusively uses renewable materials as consumables. Shellac is a low-cost renewable biomaterial that features medium hydrophilicity (e.g., a water contact angle of ca. 73°) and a high chemical stability with respect to common solvents such as cyclohexane or toluene, rendering it an interesting candidate for low-cost microfluidics and a competitor to well-known systems such as paper-based or polydimethylsiloxane-based microfluidics. Moreover, its high replication accuracy for small features down to 30 μm lateral feature size and its ability to form smooth surfaces (surface roughness Ra = 29 nm) at low embossing temperatures (glass transition temperature Tg = 42.2 °C) enable energy-efficient hot embossing of microfluidic structures. Proof-of-concept for the implementation of shellac hot embossing as a green fabrication method for microfluidic systems is demonstrated through the successful fabrication of a microfluidic test setup and the assessment of its resource consumption.


[A system applying cyclic biaxial mechanical strain to cultured cells].
To study the response of cultured cells to the cyclical biaxial biomechanical strain, a system was made according to the principle of Winston. The system was made of culture dish, pressure cavity and step motor. The culture dishes were made of polymethyl methacrylate and the bottom of the culture dishes were made of silicone rubber membrane. When the diameter of the silicone rubber tube and the distance between rollers and curvilinear plate changed, the pressure in the pressure cavity changed and the strain of the membrane changed from 0 to 4%. When the roll of the step motor changed, the frequency of the strain changed from 0.1 to 5 Hz.


Persistence of chlorpyrifos in a mineral and an organic soil.
Chlorpyrifos (Lorsban emulsifiable concentrate) was applied at 3.4 kg AI/ha and incorporated into sand and muck soil contained in small field plots. Soil samples were taken at intervals over 2 yr. Radishes and carrots, seeded yearly, served as indicator crops for absorption of insecticide residues. Samples were extracted and analyzed, by gas-liquid chromatography, for chlorpyrifos, oxychlorpyrifos, and 3,5,6-trichloro-2-pyridinol. Chlorpyrifos residues declined rapidly, with 50% of the initial application remaining after 2 and 8 wk in sand and muck, respectively, and 4 and 9% after 1 yr. Pyridinol residues increased to 13 and 39% of the initial chlorpyrifos application in sand and muck after 1 and 8 wk, respectively, and declined thereafter. Oxychlorpyrifos was detected in the 2 soils at very low levels only in immediate posttreatment samples. In the first year of the study low levels (less than 0.1 ppm) of chlorpyrifos and the pyridinol were detected in radishes and carrots.


An electrical circuit model for simulation of indoor radon concentration.
In this study, a new model based on electric circuit theory was introduced to simulate the behaviour of indoor radon concentration. In this model, a voltage source simulates radon generation in walls, conductivity simulates migration through walls and voltage across a capacitor simulates radon concentration in a room. This simulation considers migration of radon through walls by diffusion mechanism in one-dimensional geometry. Data reported in a typical Greek house were employed to examine the application of this technique of simulation to the behaviour of radon.


Epigenetic Modifications Related to Potato Skin Russeting.
Potato tuber skin is a protective corky tissue consisting of suberized phellem cells. Smooth-skinned varieties are characterized by a clean, shiny appearance compared to the darker hue of russeted potatoes. The rough skin of russeted cultivars is a desired, genetically inherited characteristic; however, unwanted russeting of smooth-skinned cultivars often occurs under suboptimal growth conditions. The involvement of epigenetic modifiers in regulating the smooth skin russeting disorder was tested. We used smooth-skin commercial cultivars with and without the russeting disorder and three lines from a breeding population segregating for russeting. Anatomically, the russet skin showed similar characteristics, whether the cause was environmentally triggered or genetically determined. The old outer layers of the corky phellem remain attached to the newly formed phellem layers instead of being sloughed off. Global DNA methylation analysis indicated a significant reduction in the percentage of 5-methylcytosine in mature vs. immature skin and russet vs. smooth skin. This was true for both the smooth-skin commercial cultivars and the russeted lines. The expression level of selected DNA methyltransferases was reduced in accordance. DNA demethylase expression did not change between the skin types and age. Hence, the reduced DNA methylation in mature and russet skin is more likely to be achieved through passive DNA demethylation and loss of methyltransferase activity.


Establishment of relationships between native and inhalation device specific spirometric parameters as a step towards patient tailored inhalation device selection.
Drug emission from DPIs is dependent on the inspiratory flow parameters through them, which are not directly measured by standard spirometry. Their estimation based on native spirometric data could help in choosing the appropriate device and optimizing the drug deposition. The aim of this study was to survey patient preferences and to find correlations between breathing parameters of COPD patients through DPI devices and their baseline spirometric data, age, gender, disease severity and anthropometric characteristics. Another objective was to establish relationships between peak inspiratory flows (PIFdev) through Breezhaler®, Genuair® and Turbuhaler® inhalers and their determinants. Breathing parameters of 49 patients with previously diagnosed COPD and currently using one of the above inhalers were recorded by normal spirometry and while inhaling through the selected DPIs. Statistical analysis of the measured data was completed. All specific data are provided as (mean ± standard deviation). More than 60% of the patients stated that their current device is the easiest to use. The means of the measured PIFdev values were 91.4 L/min, 77.1 L/min and 77.5 L/min for Breezhaler®, Genuair®, and Turbuhaler®, respectively. PIFdev values were significantly higher for males than for females, but differences upon age, BMI and disease severity group were not significant (at p = 0.05). Peak inspiratory flows through the inhalers (PIFdev) correlated best with their native spirometric counterparts (PIF) and linear PIFdev-PIF relationships could be determined (Breezhaler®: r = 0.60, p = 0.002, Genuair®: r = 0.55, p = 0.001, Turbuhaler®: r = 0.57, p = 0.002). Physical background of the deduced equations was also provided. Present correlations may be used to assess the success of inhalation of COPD patients through the studied devices and to choose the appropriate device for each patient. As a consequence, the amount of the drug emitted by the device can be optimized, the deposition efficiency within the lungs increased and the related therapeutic effect improved.


[Cytochemical study of glycogen in the leukocytes in viral hepatitis].
Glycogen in 70 patients with viral hepatitis was cytochemically established. Its content proved to be increased, not directly associated with the severity of the disease. The corticoid treatment applied had no essential effect on glycogen content.


Fake-news-free evidence-based communication for proper vein-lymphatic disease management.
Published scientific evidence demonstrate the current spread of healthcare misinformation in the most popular social networks and unofficial communication channels. Up to 40% of the medical websites were identified reporting inappropriate information, moreover being shared more than 450,000 times in a 5-year-time frame. The phenomenon is particularly spread in infective diseases medicine, oncology and cardiovascular medicine. The present document is the result of a scientific and educational endeavor by a worldwide group of top experts who selected and analyzed the major issues and related evidence-based facts on vein and lymphatic management. A section of this work is entirely dedicated to the patients and therefore written in layman terms, with the aim of improving public vein-lymphatic awareness. The part dedicated to the medical professionals includes a revision of the current literature, summing up the statements that are fully evidence-based in venous and lymphatic disease management, and suggesting future lines of research to fulfill the still unmet needs. The document has been written following an intense digital interaction among dedicated working groups, leading to an institutional project presentation during the Universal Expo in Dubai, in the occasion of the v-WINter 2022 meeting.


Morphological, Chemical Surface, and Diffusive Transport Characterizations of a Nanoporous Alumina Membrane.
Synthesis of a nanoporous alumina membrane (NPAM) by the two-step anodization method and its morphological and chemical surface characterization by analyzing Scanning Electron Microscopy (SEM) micrographs and X-Ray Photoelectron Spectroscopy (XPS) spectra is reported. Influence of electrical and diffusive effects on the NaCl transport across the membrane nanopores is determined from salt diffusion measurements performed with a wide range of NaCl concentrations, which allows the estimation of characteristic electrochemical membrane parameters such as the NaCl diffusion coefficient and the concentration of fixed charges in the membrane, by using an appropriated model and the membrane geometrical parameters (porosity and pore length). These results indicate a reduction of ~70% in the value of the NaCl diffusion coefficient through the membrane pores with respect to solution. The transport number of ions in the membrane pores (Na⁺ and Cl-, respectively) were determined from concentration potential measurements, and the effect of concentration-polarization at the membrane surfaces was also considered by comparing concentration potential values obtained with stirred solutions (550 rpm) and without stirring. From both kinds of results, a value higher than 0.05 M NaCl for the feed solution seems to be necessary to neglect the contribution of electrical interactions in the diffusive transport.