Open Source Seed, a Revolution in Breeding or Yet Another Attack on the Breeder's Exemption?
The Open Source Seed Initiative was initiated in 2012. Following concerns about the concentration in the seed sector and the rise of patenting, the initiative is "dedicated to maintaining fair and open access to plant genetic resources worldwide in order to ensure the availability of germplasm to farmers, gardeners, breeders, and communities of this and future generations." Inspired by the debate on the anti-commons and the open source software movement, the initiative wants to create a viral system to "free" genetic resources: the use of "freed" genetic resources is made conditional to any materials derived from them being made available under the same "open source" conditions. This would be achieved under a "pledge" (in the USA) or a license contract (in Germany). The objective of this paper is to analyze whether these open source seed initiatives may deliver their goals. We compare the concept with the open innovation character of the plant breeder's rights system, exemplified by the breeder's exemption, and the major other open source initiative in the sector, BiOS. We also present other ways to limit negative impact of the patent system on plant breeding. We conclude that national sovereign rights on genetic resources may challenge the open source goals and that the German initiative may contribute to legal complexities in the seed sector. The open source movement may even contribute to the trend that openness (through the breeder's exemption) is challenged despite the intentions to the contrary. In fact, the initiatives not only free the genetic resource but also treat seeds as a common good. We question the sustainability of the business models for that approach and thus the societal benefits that can be expected from plant breeding, which may illustrate the tragedy of the commons.


In vivo and ex vivo elastic properties of brain tissues measured with ultrasound elastography.
Determining the mechanical properties of brain tissues is essential in the field of brain biomechanics. In this paper, we use ultrasound-based shear wave elastography to measure both in vivo and ex vivo elastic properties of brain tissues. Our results demonstrate that the shear modulus from in vivo measurements is about 47% higher than that given by the ex vivo measurements (p value = 0.0063). The change in ex vivo elastic properties within 60-min post-mortem is negligible. The results also show that within 60-min post-mortem and in a temperature range of 37-23 °C, the elastic properties of brain tissues approximately linearly depend on the temperature in both cooling and re-heating processes.


OGM and WES identifies translocation breakpoints in PKD1 gene in an polycystic kidney patient and healthy baby delivered using PGT.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common autosomal dominant genetic diseases. Whole exome sequencing (WES) is a routine tool for diagnostic confirmation of genetic diseases, and it is usually performed to confirm the clinical diagnosis in ADPKD. Reciprocal translocation is the most common chromosomal structural abnormalities and most of its carriers have normal phenotypes until they are encountered infertility problems in adulthood. However, for the polycystic kidney disease caused by abnormal chromosome structure, WES is difficult to achieve the purpose of gene diagnosis. ADPKD-related genes were detected by WES; Chromosomal karyotyping and Optical Genome Mapping (OGM) were used to detect structural variant; The genomic break-point locations and the abnormal splicing were detected by reverse transcription-PCR and Sanger sequencing; The karyomapping gene chip and Next-Generation Sequencing (NGS) were performed to screen aneuploidy and to distinguish the non-carrier embryos from the carrier embryos. No pathogenic variant was found after the first round of WES analysis. Karyotyping data showed 46, XX, t (16; 17) (p13.3; q21.3). With the help of OGM, the translocation breakpoint on chromosome 16 was located within the PKD1 gene. With re-analysis of WES raw data, the breakpoint of translocation was verified to be located at the c.10618 + 3 of PKD1 gene. Based on this molecular diagnosis, a non-carrier embryo was selected out from three blastocysts. With preimplantation genetic testing (PGT) after in vitro fertilization (IVF), it was then transferred into uterus. With confirmation by prenatal and postnatal testing, the pedigree delivered a healthy baby. We identified a case of ADPKD caused by balanced translocation and assisted the patient to have a healthy child. When the phenotype was closely related with a monogenic disease and the WES analysis was negative, chromosomal structural analysis would be recommended for further genetic diagnosis. Based on the precision diagnosis, preventing the recurrence of hereditary diseases in offspring would be reachable.


Long-term Health Risks of Cancer in Ukraine: Insights from the 2011 Fukushima Triple Disaster Experience.
The ongoing Russo-Ukrainian War and the Great East Japan Earthquake and the subsequent accident at the Fukushima Daiichi Nuclear Power Plant in Japan have many similarities, such as mass evacuation, family separation, difficulty in accessing necessary medical care, and reduced health priorities. Although several studies have reported concerns about the short-term health impacts of the war on patients with cancer, little has been noted about the long-term effects it may cause. Given the experience of the Fukushima accident, it is important to establish a long-term support system for patients with cancer in Ukraine.


Large-scale questionnaire survey of erectile dysfunction drugs in Japanese men.
Aim: The aim of the present study was to investigate the assessment of currently prescribed drugs and approaches to overall erectile dysfunction (ED) therapy. Methods: A large-scale questionnaire survey was conducted in patients with ED who had taken an ED drug in the past 2 months. Results: Of the 308 patients surveyed, 23% became aware of having ED more than 3 years ago. In the early stages, the patients frequently experienced 'anxiety and a sense of loss' and 'irritation and powerlessness'. The ED drugs taken were sildenafil and vardenafil in 65 and 31% of the patients, respectively. Although their efficacy was generally high, approximately 80% of the patients (younger patients in particular) experienced some problems with these medications. As negative assessments, the difficulty in finding a good time to take the drug and the strange sensation of the drug forcing the patient to have an erection were pointed out. Conclusion: Use of an ED drug such as tadalafil, which produces long-lasting effects and allows more spontaneity in sexual activity, will improve ED symptoms in a favorable manner, and will not only improve the self-image of the ED patients, leading to activation and fulfillment of their lives as a whole, but will also enhance the satisfaction and security of their partners. (Reprod Med Biol 2008; 7: 105-114).


Psychometric Evaluation of the Participation and Sensory Environment Questionnaire-Home Scale (PSEQ-H).
The impact of sensory processing challenges on occupational participation is underrepresented by existing measurement tools even though these outcomes are highly prioritized by families. The Participation and Sensory Environment Questionnaire-Home Scale (PSEQ-H) is a parent-report assessment designed to evaluate the impact of the sensory environment on young children's participation in home-based activities. To describe the psychometric evaluation of the PSEQ-H, including the tool's structural validity; item difficulty, discrimination, and bias; reliability; and construct validity. Psychometric field study. Community. Three hundred four parents of children ages 2-7 yr (167 parents of children with autism spectrum disorder). Parent-report PSEQ-H data were factor analyzed, calibrated using Item Response Theory, and evaluated for construct validity. The final PSEQ-H is a reliable and valid 15-item parent-report measure of the sensory environment's impact on children's dressing, self-care, sleep, and social and play activities. The PSEQ-H can be used to plan and evaluate the effectiveness of interventions for reducing the impact of the sensory environment on children's participation in home-based tasks and activities. The PSEQ-H measures how young children's sensory environments influence their participation at home. The measure can be used to plan and evaluate occupational therapy interventions that aim to reduce sensory processing-related barriers to children's completion of developmentally salient activities.


Long QT syndrome: an indication for cervicothoracic sympathectomy.
Beta-blockade represents the primary treatment modality in patients with long QT syndrome, but left cervicothoracic sympathectomy (LCS) has been employed in refractory cases and in cases with malignant arrhythmias. LCS was performed in ten patients (six male, four female) with long QT syndrome, ranging in age from 1 month to 40 years (median 15 years). Familial long QT syndrome was present in seven patients (70%). The mean(s.e.m.) (range) preoperative corrected QT interval (QTc) was 0.52(0.01) (0.46-0.60)s. The mean(s.e.m.) duration of symptoms was 4.4(1.1) years with a mean(s.e.m.) of 4.1(0.9) syncopal episodes and 1.2(0.2) cardiac arrests per patient. LCS was carried out for refractory symptoms on beta-blockers in nine cases; a single patient was unable to tolerate beta-blockers and LCS represented the primary treatment modality. A left supraclavicular approach was utilized in each patient, resecting a portion of the stellate and all of the T2 and T3 ganglia. The median(range) length of hospitalization following operation was 2(2-6) days. There were no unexpected complications of operation, although nine (90%) of the patients developed Horner's syndrome. The QTc decreased a mean(s.e.m.) of 0.03(0.01)s following operation (P < 0.01). The frequency of symptomatic episodes decreased from a mean(s.e.m.) of 7.1(3.1)/year before LCS to 0.1(0.1) after operation (P < 0.001). Patients have been followed for a mean of 1.3(0.3) years, and all but one patient remains symptom-free; the youngest patient died suddenly 10 months after surgery. These results suggest that LCS is associated with significant clinical benefits in patients with long QT syndrome and the procedure should be considered when symptoms are refractory and malignant, or when contraindications to beta-blockers are present.


Surgery for chronic pancreatitis: the comparison of two high-volume centers reveals lack of a uniform operative management.
Many aspects of surgical therapy for chronic pancreatitis (CP), including the correct indication and timing, as well as the most appropriate operative techniques, are still a matter of debate in the surgical community and vary widely across different centers. The aim of the present study was to uncover and analyze these differences by comparing the experiences of two specialized surgical units in Italy and Austria. All patients operated for CP between 2000 and 2018 at the two centers involved were included in this retrospective analysis. Data regarding the clinical history and the pre- and perioperative surgical course were analyzed and compared between the two institutions. Our analysis showed a progressive decrease in the annual rate of pancreatic surgical procedures performed for CP in Verona (no. = 91) over the last two decades (from 3% to less than 1%); by contrast, this percentage increased from 3 to 9% in Vienna (no. = 77) during the same time frame. Considerable differences were also detected with regard to the timing of surgery from the first diagnosis of CP - 4 years (IQR 5.5) in the Austrian series vs two (IQR 4.0) in the Italian series -, and of indications for surgery, with a 12% higher prevalence of groove pancreatitis among patients in the Verona cohort. The comparison of the surgical attitude towards CP between two surgical centers proved that a consistent approach to this pathology still is lacking. The identification of common guidelines and labels of surgical eligibility is advisable in order to avoid interinstitutional treatment disparities.


Impact of Relative Dose Intensity of Early-phase Lenvatinib Treatment on Therapeutic Response in Hepatocellular Carcinoma.
Factors associated with response to lenvatinib have not been clarified in patients with hepatocellular carcinoma (HCC). This study retrospectively analyzed 50 patients treated with lenvatinib as first-line therapy between March 2018 and March 2019. Patients were divided into two groups by the Modified Response Evaluation Criteria in Solid Tumours (mRECIST) (responders and non-responders, whose best overall responses were complete (CR)/partial response (PR) and stable (SD)/progressive disease (PD), respectively). Factors associated with response were assessed, including the relative dose intensity 8 weeks after lenvatinib induction (8W-RDI). The best overall responses were 0/22/14/14 of CR/PR/SD/PD. Multivariate analysis revealed that only 8W-RDI was significantly associated with response. The receiver operating characteristic curve for 8W-RDI in differentiating responders from non-responders revealed a cut-off value of 75%. Patients with 8W-RDI ≥75% experienced a higher response rate and longer progression-free survival than patients with 8W-RDI <75%. Our results suggest that maintaining an RDI ≥75% during the initial 8 weeks of lenvatinib treatment has a favorable impact on response.


Chicken PRDX3 is required for proliferation of chicken embryo fibroblast cells.
1. This experiment investigated the influence of chicken PRDX3 on cell proliferation in chick embryo fibroblast cells using PRDX3 knockdown technology.2. A methyl thiazolyl tetrazolium (MTT) assay was performed to assess the effect of chPRDX3 knockdown on fibroblast proliferation. The antioxidant effect was investigated to determine if it directly mediated fibroblast cell proliferation.3. To determine the role of chPRDX3 on cell proliferation, an siRNA mediated knockdown was performed in chick fibroblast cells using an in vitro assay. The proliferation of fibroblast cells transfected with siPRDX3 #3 and siPRDX3 Mix was significantly decreased after 48 h (P < 0.01). In addition, the knockdown of chicken PRDX3 suppressed cell proliferation through an increase in oxidative stress.4. The results demonstrated that chPRDX3 is required for cell proliferation in chicken fibroblast cells. Such findings have important implications for the maintenance of chicken fibroblast cells.


Magnetic resonance imaging assessment of myocardial elastic modulus and viscosity using displacement imaging and phase-contrast velocity mapping.
Approximately half of patients experiencing congestive heart failure present with a normal left ventricular ejection fraction. Perturbations in material properties affecting ventricular pressure/volume relationships likely play an important role in the "stiff heart syndrome" yet noninvasive tools permitting the accurate assessment of myocardial elasticity are extremely limited. We developed an MRI-based technique to examine regional left ventricular stress/strain relationships by incorporating displacement-encoding with stimulated-echoes (DENSE) and phase-contrast (PC) velocity mapping and compared regional elastic moduli (EM) and viscous delay time constants (VDTCs) (N=10) with immediate postmortem direct strain gauge measurements (N=8) and global chamber compliance (literature) in normal dogs. EMs by MRI were significantly greater in papillary muscle columns when compared with lateral wall and septal locations by MRI (7.59+/-1.65 versus 3.40+/-0.87 versus 2.55+/-0.93 kPa, P<0.0001) and were in agreement with direct strain gauge measurements (3.78+/-0.93 and 2.96+/-0.88 kPa for the lateral wall and the septum, P=ns for both versus MRI). MRI-determined VDTCs were similar in the three regions (VDTC=-1.15+/-12.37 versus 3.04+/-7.25 versus 4.17+/-5.76 ms, P=ns) and did not differ from lateral and septal wall strain gauge assessment (VDTC=3.09+/-0.40 and 4.57+/-1.86 ms, P=ns for both versus MRI). Viscoelastic measurements obtained in six normal volunteers demonstrated the feasibility of this technique in humans. Noninvasive, regional assessment of myocardial stiffness using DENSE and PC velocity mapping techniques is accurate in a canine model and feasible in humans.


Repeated gentle handling or maternal deprivation during the neonatal stage increases adult male rats' baseline orofacial pain responsiveness.
Early life experiences have been found to have a long-lasting effect on brain development in adult life. The purpose of this study was to determine whether neonatal manipulation could alter orofacial pain responsiveness in adult rats METHODS: In the first 21 days of life, male rats were exposed to gentle handling or maternal deprivation (MD) procedures to establish models of handled and MD rats, respectively. The rats were assigned to three of the following experimental groups at the age of two months: intra-dental capsaicin (100 µg), intra-lip formalin (50 µL), and repeated nitroglycerin (NTG) (5 mg/rat/ip) infusion. In addition, there were three drug vehicle groups and three groups that received capsaicin, formalin, or NTG without prior handling or MD procedures. The behaviors were recorded following the pain induction. Spontaneous pain behaviors in the first phase of formalin test was significantly increased in MD (p < 0.01) and handled rats in comparison with the vehicle group (p < 0.05). The second-phase data showed that formalin-induced spontaneous pain behaviors was increased in rats- treated with MD as compared to either vehicle or handled+formalin groups (p < 0.001). Capsaicin-induced dental pulp nociception was increased in the MD group in comparison with the capsaicin (p < 0.001) and capsaicin+handled (p < 0.001) groups. Moreover, NTG-induced migraine-like behaviors symptoms were increased in the MD group as compared to control and handled groups (p < 0.05). In this study neonatal gentle handling or MD treatment increased orofacial pain in adulthood, showing early life experiences permanent effects on the development of trigeminal circuits in the brain.


Safety of arteriovenous fistulae and grafts for continuous renal replacement therapy: The Michigan experience.
Arteriovenous fistula or graft (AVF/AVG) use is widely considered contraindicated for continuous renal replacement therapy (CRRT), yet insertion of hemodialysis (HD) catheters can carry high complication risk in critically ill end-stage renal disease (ESRD) patients. Single-center analysis of 48 consecutive hospitalized ESRD patients on maintenance HD who underwent CRRT using AVF/AVG from 2012 to 2013. Primary outcome was access-related complications. Mean age was 60 years, 48% were male, and 88% required vasopressor support. Median duration of AVF/AVG use for CRRT was 4 days (range 1-34). Ten (21%) patients had access complications (5 bleeding, 5 infiltration, 1 thrombosis); 5 (10.4%) required catheter placement. Overall 31 (65%) patients survived to hospital discharge and AVF/AVG access was functional at the time of discharge in 29 (94%) patients. In our experience, use of AVF/AVG for CRRT can be performed with a low serious complication rate and low risk of access loss, potentially avoiding catheter-related complications.


[Calcifying tendinosis of the pectoralis major muscle with intraosseous migration].
Calcifying tendinosis is characterized by macroscopic deposits of hydroxyapatite within the tendon. Most cases involve the tendons of the rotator cuff, fundamentally the supraspinous tendon, and less frequently other tendons in practically any location. Cortical erosion with intraosseous migration of calcium deposits is rare. An atypical location combined with bone involvement can often lead to confusion with other processes like an infection or malignant tumor resulting in unnecessary biopsies or interventions. We present the case of a man who presented with pain and loss of function of the shoulder. Plain-film X-rays showed an erosion of the anteromedial cortex of the proximal diaphysis of the humerus with extra- and intra-osseous calcifications that made us suspect an infectious or malignant process. The findings at computed tomography, together with the clinical and radiological course, were key in enabling us to recognize this atypical presentation of calcifying tendinosis of the pectoralis major muscle.


VNS and pregnancy: A multicentric experience of four cases.
Vagus nerve stimulation system (VNS) has been employed worldwide as adjunctive therapy in drug-resistant epileptic patients. Only nine previous pregnancies with six-positive outcomes have been reported in women with epilepsy treated with VNS since 1998. To communicate the experience of pregnancies in women treated with VNS in our country. Clinical data of four female patients treated with VNS during pregnancy and delivery in five gestations is described. Four pregnancy outcomes were positive and one ended in spontaneous abortion, probably more related to the use antiepileptic drugs than VNS itself. Two births were vaginal and the other two with cesarean section. None of the complications during delivery were attributed to VNS. No teratogenicity was documented. Based on our experience VNS constitutes a safe therapy for the treatment of drug-resistant epilepsy in women of childbearing potential and during pregnancy and delivery. Larger series will be useful to confirm this finding.


100 MHz bandwidth planar laser-generated ultrasound source for hydrophone calibration.
High-frequency calibration of hydrophones is becoming increasingly important, both for clinical and scientific applications of ultrasound, and user safety. At present, the calibrations available routinely to the user community extend to 60 MHz. However, hydrophones that can measure beyond this are available, and ultrasonic fields often contain energy at higher frequencies, e.g., generated through nonlinear propagation of high-amplitude ultrasound used for therapeutic applications, and the increasing use of higher frequencies in imaging. Therefore, there is a need for calibrations up to at least 100 MHz, to allow ultrasonic fields to be accurately characterized, and the risk of harmful bioeffects to be properly assessed. Currently, sets of focused piezoelectric transducers are used to meet the pressure amplitude and bandwidth requirements of Primary Standard calibration facilities. However, when the frequency is high enough such that the size of the ultrasound focus becomes less than the hydrophone element's diameter, the uncertainty due to spatial averaging becomes significant, and can be as high as 20% at 100 MHz. As an alternate to piezoelectric transducers, a laser-generated ultrasound calibration source was designed, fabricated, and characterized. The source consists of an optically absorbing carbon-polymer nanocomposite excited by a large-diameter 1064 nm laser pulse of 2.6 ns duration. Peak pressure amplitudes of several Mega-Pascal were readily achievable, and the signal contained measurable frequency components up to 100 MHz. The variation in the pressure amplitudes was less than 2% from its mean over a three-hour test period. The ultrasound beam was sufficiently broad that the uncertainties due to spatial averaging were negligible.


The roles of noncoding RNA Rli60 in regulating the virulence of Listeria monocytogenes.
Listeria monocytogenes (LM) is an important zoonotic foodborne pathogen. Noncoding RNA (ncRNA) has an important role in regulating its virulence. As a member of ncRNA, however, the function of Rli60 in regulating LM virulence remain unclear. The aim of this study was to investigate the role of Rli60 in regulating LM virulence. Using a homologous recombination method, a LM EGD-e rli60 gene deletion strain (LM-Δrli60) was constructed and compared with a LM EGD-e strain in the following respects: (1) adhesiveness, invasion ability, intracellular survival, proliferation, and transcription of virulence genes in the mouse macrophage cell line RAW264.7; (2) 50% lethal dose (LD50) to the BALB/c mouse; and (3) the amount in the mouse liver and spleen and the effects on pathology of mouse liver, spleen, and kidney after inoculation. The LM-Δrli60 strain had a significantly higher adhesion rate and lower invasion rate with significantly lower intracellular survival and proliferation rates in the RAW264.7 cell line, compared to the LM EGD-e strain. Inoculation with LM-Δrli60 strain significantly affected the transcription of virulence genes. The LD50 of LM-Δrli60 to BALB/c mouse was increased by 2.12 logarithmic magnitude, which indicated that the virulence in LM-Δrli60 is significantly decreased (p < 0.05). The amount of LM-Δrli60 in the liver and spleen was significantly lower than the amount of LM EGD-e in these organs (p < 0.05). The pathological damage due to LM-Δrli60 infection in the mouse liver, spleen, and kidney was lower than the damage due to LM EGD-e infection. This study confirmed that the rli60 deletion could significantly affect LM virulence, adhesion, invasion, survival, and proliferation. This suggests that Rli60 has an important role in regulating LM virulence.


Inducible nitric oxide synthase in inflammation.
Inflammation, the reaction of vascularized tissue to local injury, not only limits the effects of injury; it may also be the underlying pathological process which initiates or sustains disease. In this paper, the evidence is reviewed for a role for nitric oxide (NO) as a chemical indicator of inflammation and inflammatory diseases.


Effects of graded compression on intraneural blood blow. An in vivo study on rabbit tibial nerve.
Compression applied to a peripheral nerve may easily interfere with intraneural blood flow. In the present experimental study, a vital microscopic technique was used to observe changes in intraneural microcirculation (intrafascicularly and extrafascicularly) when graded compression was applied to a rabbit's tibial nerve by a specially designed minicompression device. Interference with venular flow was observed already at a pressure of 20 to 30 mm Hg while arteriolar and intrafascicular capillary flow was impaired at about 40 to 50 mm Hg. At 60 to 80 mm Hg no blood flow could be observed in the nerve. Nerves observed 3 or 7 days after 2 hours of compression at 400 mm Hg showed no or very slow stagnant blood flow within the previously compressed segment. It is concluded that acute compression of nerve may cause persistent impairment of intraneural microcirculation due to mechanical injury to blood vessels.


Effects of beta-alanine supplementation on Yo-Yo test performance: A meta-analysis.
The aim of this meta-analysis was to explore the effects of beta-alanine supplementation on Yo-Yo test performance. Nine databases were searched to find relevant studies. A random-effects meta-analysis of standardized mean differences (SMD) was performed for data analysis. Subgroup meta-analyses were conducted to explore the effects of beta-alanine supplementation duration on Yo-Yo test performance, and the effects of beta-alanine supplementation on performance only in Yo-Yo level 2 test variants. Ten study groups were included in the meta-analysis. All studies included athletes as study participants. When considering all available studies, there was no significant difference between the placebo/control and beta-alanine groups (SMD: 0.68; 95% confidence interval [CI]: -0.30, 1.67). When considering only the studies that used supplementation protocols lasting between 6 and 12 weeks, there was a significant ergogenic effect of beta-alanine (SMD: 1.02; 95% CI: 0.01, 2.05). When considering only the studies that used the level 2 variants of the Yo-Yo test, there was a significant ergogenic effect of beta-alanine (SMD: 1.41; 95% CI: 0.35, 2.48). This meta-analysis found that beta-alanine is ergogenic for Yo-Yo test performance in athletes when the supplementation protocol lasts between 6 and 12 weeks and when using the level 2 variants of the Yo-Yo test.


Opportunities for histone deacetylase inhibition in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. ALS patients suffer from a progressive loss of motor neurons, leading to respiratory failure within 3 to 5 years after diagnosis. Available therapies only slow down the disease progression moderately or extend the lifespan by a few months. Epigenetic hallmarks have been linked to the disease, creating an avenue for potential therapeutic approaches. Interference with one class of epigenetic enzymes, histone deacetylases, has been shown to affect neurodegeneration in many preclinical models. Consequently, it is crucial to improve our understanding about histone deacetylases and their inhibitors in (pre)clinical models of ALS. We conclude that selective inhibitors with high tolerability and safety and sufficient blood-brain barrier permeability will be needed to interfere with both epigenetic and non-epigenetic targets of these enzymes. LINKED ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc.


Plasma metabolomics are associated with metabolic syndrome: A targeted approach.
Advances in metabolomic tools have allowed us to gain a more comprehensive understanding of metabolic syndrome (MetS). The aim of this study was to evaluate the association between plasma metabolomic profiles and MetS. For this study, adults without diabetes, chronic kidney disease, stroke, heart disease, or cancer and with full metabolomics, biochemical, and dietetic data available, representing a subsample of the Health Survey of Sao Paulo study (ISA-Capital; N = 130), were included. The joint interim statement consensus criteria were used for diagnosing MetS. Absolute quantification (µmol/L) of blood metabolites was achieved by targeted quantitative profiling of annotated metabolites by electrospray ionization tandem mass spectrometry in plasma samples. Mean differences in the compounds for MetS were evaluated by linear regression adjusted for confounding factors. Serine was inversely associated with MetS (β = -15.04; P = 0.014). In glycerophospholipids with acyl-alkyl bonds, there was an inverse association with MetS, including phosphatidylcholine (PC) ae C42:5 (β = -0.15; P = 0.040), PC ae C44:5 (β = -0.15; P = 0.046), PC ae C40:4 (β = -0.21; P = 0.014) and PC ae C44:4 (β = -0.04; P = 0.032). Plasma metabolomic profiles were associated with MetS, especially the amino acid serine and some acyl-alkyl PCs.


Circulating and thymic CD4 CD25 T regulatory cells in myasthenia gravis: effect of immunosuppressive treatment.
Accumulating evidence indicates an immunosuppressive role of the thymus-derived CD4+ T-cell population constitutively expressing high level of CD25, T regulatory (Treg) cells, in autoimmune diseases. Here we show that the number of Treg cells in the blood is significantly lower in untreated myasthenia gravis patients than in age-matched healthy subjects, whereas it is normal or elevated in patients on immunosuppressive therapy (prednisone frequently associated with azathioprine). Therapeutic thymectomy (Tx) for either the thymoma or non-neoplastic thymic alterations that are often associated with myasthenia gravis provided unique material for studying intrathymic Treg cells and correlating them with their peripheral counterparts. We observed that Tx prevents the increase of Treg cells in the circulation that follows immunosuppressive therapy (particularly evident if the thymus is not neoplastic), indicating that the thymus contributes to Treg-cell normalization. However, thymic Treg cells are not modulated by immunosuppressive therapy and even in thymectomized patients Treg-cell numbers in the blood eventually recover. The present findings suggest that a deficiency in Treg cells favours the development of myasthenia gravis and that their normalization is an important clinical benefit of immunosuppressive therapy. Treg normalization appears to be largely thymus independent and possibly reflects the reported capacity of corticosteroids to promote Treg-cell development.


Design and psychometrics of risk assessment tool for makeshift hospitals: Focusing on pandemics.
Pandemics caused a change in the health service delivery system. In disasters with massive injuries or epidemic, the capacity to admit the injured and infected patients to provide health services faces the challenges. Covid-19 virus is a respiratory disease that from its emergence until January 18, 2023, the Covid-19 virus has infected more than 672 million people worldwide. In most countries, makeshift hospital has been set up as intermediate medical centers to keep people who are likely to be carriers of the disease to control communicable diseases. Most makeshift hospitals already have alternative uses and, have changed into temporary or intermediate care centers. Based on the search of research team, any standard tools were found to assess the makeshift hospitals safety. All the safety assessment tools were related to the hospital, but since makeshift hospitals are mostly non-hospital structures, the research team has designed and validate a makeshift hospital safety assessment tool for the first time in this study. The present study is a mixed method that was conducted in 3 phases including; a document review, explaining the components affecting non-structural and functional safety of the makeshift hospital, designing makeshift hospital safety assessment tools and analyzing the results and validating it in 2022. Content validity and reliability were measured by CVR and CVI, ICC and Cronbach's alpha. In the fourth phase, with the participation of 15 specialists, managers, experts, qualitative and quantitative validity of content was done. Data were analyzed by SPSS version 21 software. The final tool contains 186 items and a 5-point Likert designed for very low safety (1), low safety (2), moderate safety (3), good safety (4), and very good safety (5). The scores of each makeshift hospital were calculated based on the items and the degree of safety. Cronbach's alpha coefficient for tool was 0.98. Retesting the questionnaire after two weeks confirmed the stability of tool (ICC = 0.98). The validity and reliability of this tool were confirmed with 186 items in 2 factors and 26 subcategories including risk of disaster, non-structural safety, safety of windows and shutters, hospital access, information and communication management, patient safety and hygiene and etc. All centers providing health services, whether temporarily or permanently, must have safety to continue their activities in disaster and maintain the safety and health of staff and inpatients. The makeshift hospital safety tool can be a suitable tool for assessing the risk and eliminating their vulnerabilities, and it can also provide important indicators for the design and set up of the makeshift hospital to policymakers and executives in the field of health.


Endovascular treatment of spontaneous isolated dissecting aneurysm of the superior mesenteric artery using stent-assisted coil embolization.
Spontaneous isolated dissecting aneurysm of the main trunk of the superior mesenteric artery is a rare condition. We treated a patient with this condition successfully by stent-assisted coil embolization. Intravascular stent placement may widen the indications for endovascular coiling of the aneurysmal false lumen to avoid perforation.


Clinical presentation and outcome of patients with enteric-type adenocarcinoma of the lung: A pooled analysis of published cases.
Enteric-type adenocarcinoma of the lung (lung-ETAC, former pulmonary enteric adenocarcinoma, PEAC) is a rare subtype of non-small cell lung cancer (NSCLC), which shares morphological and immunohistochemical features with lung and colorectal adenocarcinoma. Few data are available on patient prognosis, possible prognostic factors and systemic approach to metastatic disease. We performed a pooled analysis and a systematic review of published lung-ETAC, along with an additional case description. Thirty-one eligible publications were identified, providing data from 126 patients. In the 127 patients overall analyzed, median overall survival (OS) was 56.0 (range 36.7-75.3) months in early-stage patients and 14.0 (range 4.5-23.5) months in those with advanced/metastatic disease. Median disease-free survival (DFS) after radical surgery was 24 (range 22.6-35.1) months. Smoking status (HR 4.304, 95% CI: 1.261-14.693, p = 0.020) and node involvement (HR 1.853, 95% CI: 1.179-2.911, p = 0.007) were the negative independent prognostic factors at multivariate analysis. As regards systemic therapies for advanced cases, no firm conclusions were drawn about the efficacy of lung cancer-oriented chemotherapy regimens as opposed to colon cancer-oriented ones. Molecular analysis of lung-ETAC revealed a relatively high mutational rate, with alterations in several druggable molecular pathways, KRAS and NRAS (31%) were the most frequently mutated oncogenes, followed by ROS1 (15%), RET (13%), BRAF (11%), EGFR (8%) and ALK (6%). Moreover, 3 (15%) out of 20 cases showed DNA mismatch repair deficiency (dMMR). In conclusion, advanced lung-ETAC patients appeared to have a better prognosis compared to other subtypes of NSCLC. Moreover, the mutational rate and microsatellite instability found in lung-ETACs suggest that a significant proportion of these patients could benefit from target therapies and immunotherapy.


[Psychiatric outpatient consultation-liaison services--how do they work and what are their effects: results of a pilot study?].
Many patients benefit from interventions performed by the psychiatric liaison service. Prospective longitudinal study of community dwelling elderly patients supplemented by a questionnaire answered by family members, as well as expert interviews with the members of the consultation-liaison team and semi-structured interviews with family members. The majority of patients had some benefit from the liaison psychiatric interventions, access to care was improved and lack of specialist support was reduced. In addition there was some cost offset due to prevention of admissions to nursing homes and inpatient hospital treatment. With regard to demographic developments gerontopsychiatric liaison services should be integrated into the present system of health care. This should be supported by adjusting judicial obstacles that hamper such strategies.


Digital Control and Demodulation Algorithm for Compact Open-Loop Fiber-Optic Gyroscope.
With the advantages of small size, low cost, and moderate accuracy, an open-loop fiber-optic gyroscope (FOG) has a wide range of applications around control and automation. For the most cost-sensitive applications, a simple and stable digital algorithm with a reduced control-circuit volume and cost is highly desirable to realize high-precision control of a FOG. In this work, a new algorithm for an open-loop FOG is proposed based on the discrete multi-point demodulation in the sinusoidal modulation period. Utilizing this algorithm, stable control and angular velocity calculation of a gyro are realized with effectively suppressed gyro error. The use of this algorithm greatly reduces the requirements for processing power and simplifies the gyro circuit. Based on this algorithm, a digital FOG with a volume of only 25 × 20 × 40 mm3 achieves a bias instability of less than 0.15°/h, an angle random walk (ARW) of less than 0.015°/√h, a start-up time of less than 1 s, and a 3 dB bandwidth beyond 160 Hz. This low-cost, compact, and high-performance gyro is sufficient to satisfy the requirements of applications in the navigation and control fields such as unmanned driving.


Correlation of Dengue Warning Signs during Febrile Phase with Rotational Thromboelastometry, Cortisol and Feritin.
Dengue mortality remains high despite monitoring against warning signs (WS). The associations of WS at febrile phase (FP) and hemorrhage at defervescence with the levels and kinetics of ROTEM, platelet count, cortisol, and ferritin were analyzed. Patients with confirmed dengue serology and WS in two centers were screened (n = 275) and 62 eligible patients were recruited prospectively over 9 months. "Vomiting" was the commonest WS (62.9%), with shortened clotting time (CT) INTEM (p = 0.01). "Hematocrit increase" showed significant prolonged CT INTEM, EXTEM, and FIBTEM (p < 0.05). "Platelet decrease" showed reduced platelet function and reduced clot amplitude at 10 min (A10) and maximum clot firmness (MCF) in INTEM and EXTEM (p < 0.001). The kinetics were reduced in platelet count, CT EXTEM, and cortisol (p < 0.05) but increased in CT INTEM (p = 0.03). At FP, "vomiting", "hematocrit increase", and "platelet decrease" demonstrated impaired CT, clot strengths A10/MCF and platelet functions. Majority (60/62, 96.7%) had non-severe outcomes, consistent with increase in cortisol kinetics. In conclusion, "vomiting", "hematocrit increase" and "platelet decrease" at FP correlated with ROTEM. No conclusion could be made further regarding ferritin and cortisol. Larger study is required to study "hematocrit increase" with ROTEM as a potential marker for hemorrhage.


Effect of compassion competence on cultural competence in student nurses: Mediating effect of professional nursing values.
Cultural competence is an essential component of nursing care in today's multicultural era. However, the research on nursing students' cultural competence and its related factors is very limited. This study investigated the mediating effect of professional nursing values on the relationship between compassion competence and cultural competence among nursing students. A cross-sectional and correlational research design was used. Participants were 146 nursing students recruited from three 4-year baccalaureate nursing programs, who completed the self-report scales of compassion competence, professional nursing values, and cultural competence. Baron and Kenny's regression method and the Sobel test were used to analyse the mediating effects of professional nursing values on the association between compassion competence and cultural competence. Professional nursing values exerted a partial mediating effect on the relationship between compassion competence and cultural competence. Nursing educators should recognize that the cultural competence of nursing students can be improved by incorporating professional nursing values and compassion competence in the nursing curriculum.


Retrotransposons: mobile and mutagenic from conception to death.
Mobile genetic elements feature prominently in mammalian genome evolution. Several transposition-competent retrotransposon families (L1, Alu, SVA) remain active in the human germ line, leading to pathogenesis as well as genome structural variation across the global population. High-throughput screening approaches have recently been developed to detect retrotransposon insertion polymorphisms. Evidence produced by these and other genome-scale technologies indicates an expanded role for retrotransposition in human biology, including somatic mobilisation in the developing embryo and in neural cells.


Herman J. C. Berendsen, a Very Modest Genius.
This letter gives a description of my interactions with Herman over more than 30 years. His teaching, his tremendous insight in subjects newly presented to him, his generousness, his playful interactions with colleagues and students, the freedom in research direction that he allowed and also expected from his PhD students.


Decyl-ammonium octa-noate.
The title compound, C(10)H(24)N(+)·C(8)H(15)O(2) (-), forms a layered structure in which inter-molecular N(+)-H⋯O hydrogen bonds connect anions and cations, forming a two-dimensional network parallel to (010). The n-alkyl chains of the decyl-ammonium cations pack according to an ortho-rhom-bic 'subcell' with approximate dimensions 5.1 × 7.3 Å, and they are significantly distorted from planarity.


U3 snoRNA-mediated degradation of ZBTB7A regulates aerobic glycolysis in isocitrate dehydrogenase 1 wild-type glioblastoma cells.
The isocitrate dehydrogenase (IDH) phenotype is associated with reprogrammed energy metabolism in glioblastoma (GBM) cells. Small nucleolar RNAs (snoRNAs) are known to exert an important regulatory role in the energy metabolism of tumor cells. The purpose of this study was to investigate the role of C/D box snoRNA U3 and transcription factor zinc finger and BTB domain-containing 7A (ZBTB7A) in the regulation of aerobic glycolysis and the proliferative capacity of IDH1 wild-type (IDH1WT ) GBM cells. Quantitative reverse transcription PCR and western blot assays were utilized to detect snoRNA U3 and ZBTB7A expression. U3 promoter methylation status was analyzed via bisulfite sequencing and methylation-specific PCR. Seahorse XF glycolysis stress assays, lactate production and glucose consumption measurement assays, and cell viability assays were utilized to detect glycolysis and proliferation of IDH1WT GBM cells. We found that hypomethylation of the CpG island in the promoter region of U3 led to the upregulation of U3 expression in IDH1WT GBM cells, and the knockdown of U3 suppressed aerobic glycolysis and the proliferation ability of IDH1WT GBM cells. We found that small nucleolar-derived RNA (sdRNA) U3-miR, a small fragment produced by U3, was able to bind to the ZBTB4 3'UTR region and reduce ZBTB7A mRNA stability, thereby downregulating ZBTB7A protein expression. Furthermore, ZBTB7A transcriptionally inhibited the expression of hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), which are key enzymes of aerobic glycolysis, by directly binding to the HK2 and LDHA promoter regions, thereby forming the U3/ZBTB7A/HK2 LDHA pathway that regulates aerobic glycolysis and proliferation of IDH1WT GBM cells. U3 enhances aerobic glycolysis and proliferation in IDH1WT GBM cells via the U3/ZBTB7A/HK2 LDHA axis.


Involvement of CD8+ T cells in delayed-type hypersensitivity responses against bovine leukemia virus (BLV) induced in sheep vaccinated with recombinant vaccinia virus expressing BLV envelope glycoprotein.
Delayed-type hypersensitivity responses against bovine leukemia virus (BLV) envelope glycoprotein (gp60) were induced in the skin of sheep vaccinated with recombinant vaccinia virus (RVV) expressing BLV glycoprotein. The lesions were characterized by marked infiltration of lymphocytes, slight migration of neutrophils, eosinophils, and macrophages in the dermis to hypodermis, and partial intercellular edema in the reticular layer. Immunohistochemical analysis with monoclonal antibodies demonstrated that the lymphocytic infiltrates consisted mainly of CD8+ T cells (53.7-55.8% at 48 hours post-challenge of BLV), CD4+ T cells (24.7-26.7%), and B cells (11.5-16.9%). The role of CD4+ and CD8+ T cells in suppressing BLV growth in RVV-vaccinated animals is discussed.


Circulating miRNA profiles in patients with metabolic syndrome.
Coordinated interplay of dysregulated microRNAs in isolated metabolic disorder is implicated in the pathogenesis of metabolic syndrome. The objective of the study was to characterize microRNA expression in the blood and exosomes of individuals with metabolic syndrome and compare them with those manifesting one of the metabolic vascular risk factors (type 2 diabetes, hypercholesterolemia, or hypertension). RESEARCH DESIGN/SETTING/PARTICIPANTS: A total of 265 participants were recruited in a health screening and characterized into distinct groups as follows: 1) healthy controls (n = 46); 2) metabolic syndrome (n = 50); 3) type 2 diabetes (n = 50); 4) hypercholesterolemia (n = 89); and 5) hypertension (n = 30). Total RNA was subjected to microRNA profiling, and a panel of significantly dysregulated microRNAs was validated using quantitative PCR. Analysis of profiling data characterized unique pools of miRNAs that could categorize the different risk factors of metabolic syndrome. We have identified miR-197, miR-23a, and miR-509-5p as potential contributors of dyslipidemia in metabolic syndrome (correlation with body mass index; P = 0.029, 0.021, and 0.042, respectively) and miR-130a and miR-195 as contributors of hypertension (correlation with blood pressure; P = 0.019 and 0.045, respectively). A plausible association of miR-27a and miR-320a with metabolic syndrome and type 2 diabetes patients has also been found because these miRNAs remained dysregulated in both cases (correlation with fasting glucose; P = 0.010 and 0.016, respectively). Significant dysregulation of seven candidate microRNAs has been found to be associated with risks involved in the manifestation of metabolic syndrome.


The endogenous pyrogens in host-defense interactions.
Soluble factors produced by activated macrophages serve to marshal host defenses against infection, injury, or inflammation, but they may also cause chronic inflammation or even lethal shock. Suppressing or enhancing such cytokine functions has important therapeutic potential in, respectively, chronic inflammatory and immunologically deficient states.


Faced with the corona virus pandemic, those leaving in total exclusion of our modern societies express various needs other than food: needs of reference points, communication, care and recognition of human dignity. It is our responsibility to consider these needs as essential.


Physiology of Erection and Pathophysiology of Erectile Dysfunction.
The science of penile erection, including recent advances in its molecular physiology and neuroanatomic pathways, is described. The pathophysiology of erectile dysfunction is presented, acknowledging associated disease states, and accordingly follows a practical classification scheme: vasculogenic, neurogenic, endocrine, and psychogenic.


The impact of graphomotor demands on letter-like shapes recognition: A comparison between hampered and normal handwriting.
Recent research suggests that graphic motor programs acquired through writing are part of letter representations and contribute to their recognition. Indeed, learning new letter-like shapes through handwriting gave rise to better recognition than learning through methods suppressing the graphomotor activity (e.g., typing or viewing). The present study aimed at further assessing the role of the graphic motor programs in letter-like shape recognition by disturbing the graphomotor activity during learning. We compared recognition performance following normal handwriting to recognition performance following hampered handwriting. Adult participants learned sets of symbols by copying them either with a standard pen or with a hampering writing tool. Recognition tests were administered immediately after the learning phase and again one week later. The results revealed lower recognition accuracy following hampered handwriting than following normal handwriting suggesting a contribution of graphomotor skills in the construction of letter representation.


Prognostic Value of Multilayer Left Ventricular Global Longitudinal Strain in Patients with ST-segment Elevation Myocardial Infarction with Mildly Reduced Left Ventricular Ejection Fractions.
Multilayer (epi-, mid- and endocardium) left ventricular (LV) global longitudinal strain (GLS) reflects the extent of myocardial damage after ST-segment myocardial infarction (STEMI). However, the prognostic implications of multilayer LV GLS remain unclear. We studied the association between multilayer LV GLS and prognosis in patients with mildly reduced or preserved LV ejection fraction (EF) after STEMI. Patients with first STEMI and LVEF>45% were evaluated retrospectively. Baseline multilayer (endocardial, mid-myocardial and epicardial) LV GLS were measured on 2-dimensional speckle tracking echocardiography. Patients were followed up for of all-cause mortality. A total of 569 patients (77% male, 60 ± 11 years) were included. After a median follow-up of 117 (interquartile range 106-132) months, 95 (17%) patients died. We observed no differences in baseline LVEF and peak troponin levels between survivors and non-survivors. However, non-survivors showed more impaired GLS at all layers (epicardium: -11.9 ± 2.8% vs. -13.4 ± 2.8%; mid-myocardium: -14.2 ± 3.2% vs. -15.6 ± 3.2%; endocardium: -16.5 ± 3.7% vs. -17.7 ± 3.6%, p <0.05, for all). On multivariable analysis, increasing age (hazard ratio 1.095; p<0.001) and impaired LV GLS of the epicardial layer (hazard ratio 1.085; p = 0.047) were independently associated with higher risk of all-cause mortality. In addition, LV GLS at the epicardium had incremental prognostic value for all-cause mortality (χ2 = 114, p = 0.044). In conclusion, in contemporary STEMI patients with mildly reduced or preserved LVEF, ageing and reduced LV GLS of the epicardium (reflecting transmural scar formation) were independently associated with all-cause mortality after adjusting for clinical and echocardiographic variables.


The effect of collagenase on surface markers of human peripheral lymphocytes.
The effect of collagenase on the 'T' and 'B' markers of peripheral blood lymphocytes was studied in five healthy male blood donors. No significant difference between untreated and collagenase treated lymphocytes was found. Collagenase is recommended for use in liberating living cells from skin biopsy specimens.


The correlation between patent foramen ovale and brain ischemia in plateau residents.
It has been suggested that patent foramen ovale (PFO) contributes to the majority of cryptogenic stroke cases in young people, however, the direct link is still undetermined. Here we analyzed the correlation between PFO and brain ischemia lesions in a cohort of cases that were long-term residents in the plateau to provide solid evidence to support the causal relation between PFO and brain ischemia lesion or cryptogenic stroke. Long-term residents with young age from Qinghai Plateau were recruited and separated by PFO positivity. Brain MRI was used to image 100 PFO positive cases and 100 healthy controls. The diameter of PFO was measured by echocardiography. The location, number and anterior/posterior circulation of ischemia lesions were also evaluated. The correlation between PFO (including positivity and diameter) and brain ischemia lesion (including positivity and other characteristics) was analyzed by chi-square test. Further, the chi-square test for the trend test was used to analyze the linear correlation between these groups. We found a strong correlation between the positivity of PFO and brain ischemia lesion, with 71% of PFO cases showing the presence of brain ischemia lesions, and only 19% for healthy controls (p < 0.001). The diameter of PFO is strongly and linearly correlated with the incidence rate of brain ischemia lesion (RR = 3.737 (95%CI 2.496 to 5.767). We found a convincing correlation between the positivity of PFO and brain ischemia lesion in residents of the plateau. Our findings provide another solid evidence of the direct causal relation between PFO and brain ischemia lesion.


Parkinson's Disease and Diabetes Mellitus: Synergistic Effects on Pathophysiology and GI Motility.
Parkinson's disease and diabetes affect an increasing proportion of the aging global population. Both conditions extensively affect gastrointestinal (GI) motility with similar and differing clinical symptoms. Nonetheless, GI symptoms in Parkinson's disease and diabetes pose significant morbidity and impairment of quality of life. Their pathophysiology is poorly understood, and therefore, effective treatment options are lacking. Parkinson's disease patients have oropharyngeal dysphagia and constipation. They also have mild or absent upper GI symptoms associated with delayed gastric emptying, which is prevalent in 70% of patients. Delayed gastric emptying in Parkinson's disease leads to erratic medication absorption and fluctuating motor symptoms. Half of diabetics have upper GI symptoms, which correlate to gastric emptying and changes in brain activity of the insular cortex. The majority of diabetics also have constipation. Diabetics have an increased risk for developing Parkinson's disease and anti-diabetic medications are associated with risk reduction of developing Parkinson's disease. Hyperglycemia is associated with advanced glycated end products formation and acceleration of α-synuclein aggregation. GLP-1 receptor agonists have also demonstrated efficacy in improving motor symptoms and cognition in Parkinson's disease patients with diabetes. Parkinson's disease and diabetes are pan-enteric disorders with significant GI symptoms and impairment of gut motility. Both conditions have synergistic pathophysiologies that propagate neurodegenerative changes. Treatment options for GI symptoms in diabetic and Parkinson's disease patients are lacking. Anti-diabetic treatment improves motor symptoms in Parkinson's disease, however, its effect on GI symptoms is unclear.


Expression of c-Jun in dopaminergic neurons of the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice.
The expression of c-Jun in the brains of young (8-week-old) and older (52-week-old) mice following administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was investigated immunocytochemically. Both age groups exhibited reduction in the number of dopaminergic neurons in the substantia nigra after administration of MPTP. There was a significant difference in the magnitude of decrease in the number of dopaminergic neurons between the two groups, as has previously been reported, and the older mice exhibited more extensive loss of dopaminergic neurons in the substantia nigra after MPTP administration than did the young mice. Prolonged c-Jun expression was induced in the substantia nigra following administration of MPTP, and this induction was more prominent in the older mice than in the young mice. Maximum expression of c-Jun occurred on day 7 after the administration of MPTP in both groups. Double staining for tyrosine hydroxylase (TH; a dopaminergic neuron marker) and c-Jun revealed their co-localization indicating that the cells expressing c-Jun were dopaminergic neurons. Cytoplasmic volumes of strongly c-Jun positive cells were reduced, suggesting that they may have been degenerating. In situ end labeling revealed no apoptotic neurons after MPTP administration. These results suggest the existence of some cascade mechanism of nonapoptotic death of dopaminergic neurons following administration of MPTP.


Can semi-supervised learning explain incorrect beliefs about categories?
Three experiments with 88 college-aged participants explored how unlabeled experiences-learning episodes in which people encounter objects without information about their category membership-influence beliefs about category structure. Participants performed a simple one-dimensional categorization task in a brief supervised learning phase, then made a large number of unsupervised categorization decisions about new items. In all three experiments, the unsupervised experience altered participants' implicit and explicit mental category boundaries, their explicit beliefs about the most representative members of each category, and even their memory for the items encountered during the supervised learning phase. These changes were influenced by both the range and frequency distribution of the unlabeled stimuli: mental category boundaries shifted toward the middle of the range and toward the trough of the bimodal distribution of unlabeled items, whereas beliefs about the most representative category members shifted toward the modes of the unlabeled distribution. One consequence of this shift in representations is a false-consensus effect (Experiment 3) where participants, despite receiving very disparate training experiences, show strong agreement in judgments about representativeness and boundary location following unsupervised category judgments.


Health-related quality of life in 640 head and neck cancer survivors after radiotherapy using EORTC QLQ-C30 and QLQ-H&N35 questionnaires.
With the advances in modern radiotherapy (RT), many patients with head and neck cancer (HNC) can be effectively cured, and their health-related quality of life (HR-QoL) has become an important issue. In this study, we evaluated the prognosticators of HR-QoL in a large cohort of HNC patients, with a focus on the result from technological advances in RT. A cross-sectional investigation was conducted to assess the HR-QoL of 640 HNC patients with cancer-free survival of more than 2 years. Among them, 371 patients were treated by two-dimensional RT (2DRT), 127 by three-dimensional conformal RT (3DCRT), and 142 by intensity-modulated RT (IMRT). The EORTC QLQ-C30 questionnaire and QLQ-H&N35 module were used. A general linear model multivariate analysis of variance was used to analyze the prognosticators of HR-QoL. By multivariate analysis, the variables of gender, annual family income, tumor site, AJCC stage, treatment methods, and RT technique were prognosticators for QLQ-C30 results, so were tumor site and RT technique for H&N35. Significant difference (p < 0.05) of HR-QoL outcome by different RT techniques was observed at 2 of the 15 scales in QLQ-C30 and 10 of the 13 scales in H&N35. Compared with 2DRT, IMRT had significant better outcome in the scales of global QoL, physical functioning, swallowing, senses (taste/smell), speech, social eating, social contact, teeth, opening mouth, dry mouth, sticky saliva, and feeling ill. The technological advance of RT substantially improves the head-and-neck related symptoms and broad aspects of HR-QoL for HNC survivors.


Asymptomatic Diabetic Cardiomyopathy: an Underrecognized Entity in Type 2 Diabetes.
Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF), with diabetic cardiomyopathy (DbCM) referring to abnormal heart structure in the absence of other driving cardiac factors such as hypertension, coronary artery disease (CAD), and valvular heart disease. Stage B DbCM is commonly asymptomatic and represents a form of stage B HF; DbCM thus represents a transitional phenotype prior to onset of symptomatic HF. The pathogenesis of DbCM is not fully elucidated but involves hyperglycemia, insulin resistance, increased free fatty acids (FFA), lipotoxicity, oxidative stress, advanced glycation end product (AGE) formation, activation of the renin-angiotensin-aldosterone system (RAAS) with an increase in angiotensin II, and dyshomeostasis of calcium, which all contribute to left ventricular hypertrophy (LVH) and cardiac systolic and diastolic dysfunction. Although DbCM is an established pathogenic process, it is underrecognized clinically due to its commonly asymptomatic nature. Raising awareness to identify high-risk individuals with stage B HF due to DbCM, who may subsequently progress to overt HF (stage C/D HF), as well as identifying new pharmacological agents and approaches to prevent functional decline, may help reduce this global health problem. The aim of this review is to focus on stage B DbCM; provide data on diagnostic approaches, current therapies, and potential therapies under investigation; and highlight the need to raise awareness and interdisciplinary dialogue among clinicians and researchers. There are no currently approved therapeutic strategies to treat or prevent progression of stage B DbCM, but multiple attempts are being made to target different pathogenic mechanisms involved in the development of DbCM. Recent cardiovascular (CV) outcome trials (CVOTs) have identified newer therapeutic agents with CV benefit, such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors that reduce hospitalization for HF and glucagon-like peptide-1 (GLP-1) receptor agonists that reduce major adverse CV events (MACE), though without consistent effect on HF outcomes. Recent clinical practice guidelines recommend screening patients at high risk for HF. Further definition and interdisciplinary discussion of high-yield populations to screen, appropriate subsequent evaluation and intervention are needed to advance this area. DbCM is a complex entity that results from multiple pathogenic mechanisms triggered by impairment of glucose and lipid metabolism over many years. DbCM is commonly asymptomatic and represents a form of stage B HF. It is an underrecognized process that may progress to functional decline and overt HF. Although newer medications approved for the treatment of T2D may play an important role in reducing the risk of HF complications, less focus has been placed on earlier recognition and treatment of DbCM while asymptomatic. Additional efforts should be made to further study and target this stage in order to decrease the overall burden of HF.


Blast2GO: a universal tool for annotation, visualization and analysis in functional genomics research.
We present here Blast2GO (B2G), a research tool designed with the main purpose of enabling Gene Ontology (GO) based data mining on sequence data for which no GO annotation is yet available. B2G joints in one application GO annotation based on similarity searches with statistical analysis and highlighted visualization on directed acyclic graphs. This tool offers a suitable platform for functional genomics research in non-model species. B2G is an intuitive and interactive desktop application that allows monitoring and comprehension of the whole annotation and analysis process. Blast2GO is freely available via Java Web Start at http://www.blast2go.de. http://www.blast2go.de -> Evaluation.


Preovulatory changes in ovarian cyclic AMP and prostaglandins in immature rats injected with PMSG.
In 28-day-old rats injected with PMSG, ovarian cyclic AMP and PGE and PGF increased 2 and 3-4 h respectively after the LH peak.


The use of synthetic oligodeoxynucleotide primers in cloning and sequencing segment of 8 influenza virus (A/PR/8/34).
Complete double-stranded DNA copies of the RNA genes of the human influenza virus A/PR/8/34 have been synthesized by using two synthetic oligodeoxynucleotide primers. The gene encoding the non-structural proteins NS1 and NS2, prepared with these primers, has been cloned into the bacteriophage M13mp7 and sequenced. The sequence is compared with that from another human strain and from an avian strain.


Woodsmoke marker levoglucosan: kinetics in a self-experiment.
Concerns on climate change are leading to the renaissance of wood burning and particulate exposures. Levoglucosan is used as a marker of woodsmoke in air and urine. Contribution of data on urinary excretion of levoglucosan, to improve biomonitoring and source apportionment of woodsmoke. 1, 3, 5, and 7 hours after 5 mg of levoglucosan had been administered orally, urinary excretion was measured by HPLC and mass spectrometry. After oral intake, urine concentrations increased rapidly, reached highest values after 3 hours, and after 7 hours approximately 70% of the administered dose was excreted. Urinary levoglucosan may be used for biomonitoring of woodsmoke exposure on the same day.


Antimony Potassium Tartrate Stabilizes Wide-Bandgap Perovskites for Inverted 4-T All-Perovskite Tandem Solar Cells with Efficiencies over 26.
Wide-bandgap (WBG) perovskites have been attracting much attention because of their immense potential as a front light-absorber for tandem solar cells. However, WBG perovskite solar cells (PSCs) generally exhibit undesired large open-circuit voltage (VOC) loss due to light-induced phase segregation and severe non-radiative recombination loss. Herein, antimony potassium tartrate (APTA) is added to perovskite precursor as a multifunctional additive that not only coordinates with unbonded lead but also inhibits the migration of halogen in perovskite, which results in suppressed non-radiative recombination, inhibited phase segregation and better band energy alignment. Therefore, a APTA auxiliary WBG PSC with a champion photoelectric conversion efficiency of 20.35% and less hysteresis is presented. They maintain 80% of their initial efficiencies under 100 mW cm-2 white light illumination in nitrogen after 1,000 h. Furthermore, by combining a semi-transparent WBG perovskite front cell with a narrow-bandgap tin-lead PSC, a perovskite/perovskite four-terminal tandem solar cell with an efficiency over 26% is achieved. Our work provides a feasible approach for the fabrication of efficient tandem solar cells.


Using Human Induced Pluripotent Stem Cell-Derived Organoids to Identify New Pathologies in Patients With PDX1 Mutations.
Two patients with homozygous mutations in PDX1 presented with pancreatic agenesis, chronic diarrhea, and poor weight gain, the causes of which were not identified through routine clinical testing. We aimed to perform a deep analysis of the stomach and intestine using organoids derived from induced pluripotent stem cells from PDX1188delC/188delC patients. Gastric fundic, antral, and duodenal organoids were generated using induced pluripotent stem cell lines from a PDX1188delC/188delC patient and an isogenic induced pluripotent stem cell line where the PDX1 point mutation was corrected. Patient-derived PDX1188delC/188delC antral organoids exhibited an intestinal phenotype, whereas intestinal organoids underwent gastric metaplasia with significant reduction in enteroendocrine cells. This prompted a re-examination of gastric and intestinal biopsy specimens from both PDX1188delC/188delC patients, which recapitulated the organoid phenotypes. Moreover, antral biopsy specimens also showed increased parietal cells and lacked G cells, suggesting loss of antral identity. All organoid pathologies were reversed upon CRISPR-mediated correction of the mutation. These patients will now be monitored for the progression of metaplasia and gastrointestinal complications that might be related to the reduced gastric and intestinal endocrine cells. This study demonstrates the utility of organoids in diagnosing uncovered pathologies.


miR-34c inhibits PDGF-BB-induced HAVSMCs phenotypic transformation and proliferation via PDGFR-β/SIRT1 pathway.
The purpose of this study was to explore the effect of miR-34c on PDGF-BB-induced HAVSMCs phenotypic transformation and proliferation via PDGFR-β/SIRT1 pathway, so as to find a new method for early diagnosis and treatment of cardiovascular disease. HA-VSMCs were treated with platelet-derived growth factor-BB (PDGF-BB) at 0 h, 12 h, 24 h, 48 h or 36 h to explore the optimal time for phenotypic transformation of VSMCs. And then, PDGF-BB-induced HA-VSMCs were transfected with miR-34c mimics/mimics NC and pcDNA3.1-PDGFR-β/pcDNA3.1-NC to observe cell biological behaviour. CCK8 was used to detect cell proliferation activity. Transwell chamber assay was used to detect cell invasion. Early apoptosis was analyzed by flow cytometry. The expression of α-SMA and Smemb was detected by immunofluorescence staining. The expressions of PDGFR-β, IRF9, Acetyl-NF-κB/p65, Acetyl-p53 and CyclinD1 were analyzed by Western blot analysis. The expression of miR-34a, miR-34b and miR-34c was detected by RT-PCR, and the targeting relationship between miR-34c and PDGFR-β was detected by luciferase reporting assay. The results indicated the proliferation and migration of PDGF-BB-induced HA-VSMCs significantly increased, and apoptosis significantly decreased. Besides, α-SMA decreased significantly, while Smemb increased significantly. Furthermore, expressions of PDGFR-β, IRF9, Acetyl-NF-κB/p65, Acetyl-p53 and CyclinD1 increased significantly, and SIRT1 decreased significantly. Experimental results showed that, miR-34c mimics significantly inhibited cell proliferation and migration, and promoted cell apoptosis, and miR-34c inhibitor had the opposite effects. MiR-34c mimics significantly increased α-SMA expression and decreased Smemb expression, while the opposite effects were reflected after transfection with miR-34c inhibitor. Moreover, miR-34c mimics significantly decreased the expressions of PDGFR-β, IRF9, Acetyl-NF-κB/p65, Acetyl-p53 and CyclinD1, and significantly increased the expression of SIRT1, while miR-34c inhibitor had the opposite effects. Luciferase assay confirmed that PDGFR-β was a potential target of miR-34c. Subsequently, PDGF-BB-induced HA-VSMCs were co-transfected with miR-34c mimics and pcDNA3.1-PDGFR-β. The results indicated that PDGFR-β reversed the biological function of miR-34c mimic. The results revealed the potential application value of miR-34c as a marker molecule of phenotypic transformation, providing a potential target for improving phenotypic transformation.


Evaluation of cerebral blood flow by single-photon emission computed tomography in young Asian Indians with hypertension.
The objective of the study was to investigate abnormalities of regional cerebral blood flow (rCBF) in young (age 33.0+/-6.3 years; range 21-45 years) non-diabetic and normolipidemic Asian Indians with hypertension. The rCBF was assessed with single-photon emission computed tomography (SPECT) in patients with hypertension (n = 33) and healthy controls (n = 20). The SPECT findings were normal in 41 subjects and showed abnormalities of cerebral perfusion in 10 subjects, all of which were hypertensive patients. These observations are extremely important for a vast number of young hypertensive patients in India. To prevent cerebrovascular accidents in future, patients with hypertension and decreased rCBF should be carefully monitored and their hypertension should be strictly controlled. These subjects may also be researched as potential candidates for preventive antiplatelet therapy.


The effectiveness of sweeping membranes at term: a randomized trial.
To determine whether sweeping or stripping membranes at 38-40 weeks' gestation leads to spontaneous labor within 7 days. One hundred fifty antenatal low-risk patients at 38-40 weeks' gestation were assigned randomly to sweeping or control (ie, Bishop score only) groups and stratified based on the ability to pass a finger through the internal os. The primary outcome was the rate of spontaneous labor within 7 days. Major secondary outcomes included the spontaneous labor rate before 41 weeks and the overall spontaneous labor rate. Other outcomes included maternal and neonatal morbidity. The sample size was calculated based on doubling of the spontaneous labor rate within 7 days from 28% to 56% (alpha = 0.05, beta = 0.10). The subjects were demographically similar between the groups. There were no differences between the groups in the primary outcome of spontaneous labor within 7 days (33% sweeping, 38% control; P = .39) or in the secondary outcomes of spontaneous labor before 41 weeks (P = .66) or the overall spontaneous labor rate (P = .09). The Bishop score predicted spontaneous labor within 7 days (P = .003), and gestational age at enrollment predicted spontaneous labor before 41 weeks (P = .008) and the overall spontaneous labor rate (P = .008), using logistic regression to control for potential confounders. Sweeping membranes once at 38-40 weeks' gestation does not significantly increase the proportion of women who begin spontaneous labor within 7 days.


[Chest radiograph in assessing the results of treatment with 6-month short-course chemotherapy of pulmonary tuberculosis].
Chest radiograph was evaluated in 287 cases of smear-positive pulmonary tuberculosis treated with 6-month short course chemotheapy. After 6-month chemotherapy was completed, the results of chest rediography were in a similar trend comparing to that of sputum examination in 94.0% cases. During 18 months follow-up in 107 (37.9%) of 282 cases, the remained shadows in chest radiography continued to resolve and in 14 (58%) of 24 cases, remained in chest radiograph were closed. It is concluded that sputum examination in assessing the results of 6 months short-course chemotherapy simple, reliable and cheaper than chest radiography.


Suction drainage culture as a guide to effectively treat musculoskeletal infection.
Following surgery for musculoskeletal infection, a positive suction drainage culture (SDC) is consistent with persistent sepsis. Our objective was to determine the effect of a negative SDC obtained in subsequent operations on the outcome of a musculoskeletal infection. 99 patients were prospectively enrolled, all treated surgically for musculoskeletal infection utilizing suction drainage and appropriate antimicrobial therapy. Surgery consisted of irrigation, debridement, and prosthetic exchange or implant removal. SDC was considered negative if all bottles resulted in negative cultures. Following SDC results, patients were placed into 1 of 2 treatment groups: 1) Negative SDC, and no new operation; or 2) Positive SDC, and new operation(s) until SDC was negative. Antibiotic therapy ranged from 6-12 weeks (osteomyelitis) to 10-21 d (soft tissue). Both groups were similar with regard to baseline characteristics. Cure was obtained in 91.8% of patients (56/61) in group 1 and 91.6% of patients (22/24) in group 2. Similar results were obtained in patients with an infection in the presence of an implant. In conclusion, a negative SDC following surgery for a musculoskeletal infection is a strong indication of eventual outcome.


Colonisation of fluoroquinolone-resistant Haemophilus influenzae among nursing home residents in southern Taiwan.
Fluoroquinolones have been widely used to treat respiratory tract infections, but fluoroquinolone resistance in Haemophilus influenzae has remained rare. In 2007, prospective surveillance cultures of throat swabs and sputum were conducted every two months on 150 residents of four nursing homes in southern Taiwan. Forty-eight H. influenzae isolates were obtained from 30 (20%) residents. All isolates were non-b serotype and 27 (56.3%) possessed beta-lactamases. Resistance to levofloxacin [minimum inhibitory concentration (MIC) >2 microg/mL] and moxifloxacin (MIC >1 microg/mL) was found in 20 (41.7%) and 21 (43.8%) isolates, respectively. High level levofloxacin and moxifloxacin resistance (MIC >32 microg/mL) was detected in 19 (39.6%) and 15 (31.3%) isolates, respectively. Among 150 residents, those with urinary catheterisation (P=0.018) and tracheostomy tubes (P=0.029) were independently associated with airway colonisation by moxifloxacin-resistant H. influenzae. Among 30 residents with carriage of H. influenzae, no factor was significantly associated with moxifloxacin resistance. Pulsed-field gel electrophoresis of the isolates revealed 14 distinct types. Two major clones accounted for 29 isolates, 27 of which were obtained from 13 residents in one nursing home. All but two of the fluoroquinolone-resistant isolates belonged to these two major clones. This study highlights the emergence of fluoroquinolone-resistant H. influenzae and its clonal spread among nursing home residents in southern Taiwan. Further studies on clinical implications and the extent of fluoroquinolone non-susceptibility and resistance are needed.


Objective excyclotorsion increases with aging in adults.
It has been reported that the disc-fovea angle (DFA), a measure of objective cyclotorsion, increases with age. DFA was measured in three age groups of adults and the effects of age, sex, and laterality on DFA is reported. A retrospective study was performed on patients who had a glaucoma checkup or who visited for suspected cataract, who underwent fundus photography between 2013 and 2021. Patients with visual acuity <0.7, axial length >27 mm, strabismus or ocular diseases affecting fusion were excluded. DFA was measured from digital fundus photographs obtained from 249 participants comprising three age groups (group I, 44.4 ± 0.5 years, n = 58; group II, 63.7 ± 3.6 years, n = 129; group III, 81.0 ± 3.8 years, n = 62). The sum of right- and left-eye DFAs is named as total DFA. Dunnett's post-hoc test after ANOVA showed that the left-eye DFA and total DFA of group III were significantly larger than those of group I (p = .01 and p < .01, respectively). Total DFA of female participant (15.6 ± 4.7°, n = 168) was significantly larger than that of male participant (13.9 ± 4.3°, n = 81) (p < .01). The DFA of the left eye (8.2 ± 3.5°, n = 249) was significantly larger than that of the right eye (6.8 ± 3.3°, n = 249) (p < .001). Group III was subdivided based on eye dominance (right eye dominance, n = 36; left eye dominance, n = 13; NA, n = 13). The DFA in the nondominant eye (9.7 ± 4.6°) was significantly larger than that in the dominant eye (7.4 ± 3.7°) (p < .01). This study found a slight increase of DFA with age. Furthermore, DFA in female or DFA in the left-eye was larger than DFA in male or in the right-eye.


Clinical features of BK-polyomavirus and cytomegalovirus co-infection after kidney transplantation.
BK polyomavirus (BKPyV) and cytomegalovirus (CMV) are the main viral pathogens affecting the graft and recipient outcome after allogenic kidney transplantation. It has recently been found that infection with both viruses has a greater impact on kidney graft function than a single infection. We retrospectively analyzed a cohort of 723 recipients who received kidney transplantation between 2007 and 2015 after living and postmortal donation for differences in risk and outcome parameters regarding BKPyV (DNAemia) and CMV (CMV DNAemia) co-infection compared to sole viremias and to patients without viremia. Of all kidney allograft recipients in our cohort, 8.2% developed co-infection with BKPyV DNAemia and CMV DNAemia, 15.1% showed BKPyV viremia alone and 25.2% sole CMV DNAemia. Acute rejection was closely linked with co-infection (multivariable analysis, p = 0.001). Despite the fact that the estimated glomerular filtration rate of patients with co-infection was noticeably reduced compared to patients with BKV or CMV infection alone, transplant survival and patient survival were not significantly reduced. Co-infection with BKPyV and CMV in kidney transplanted patients is significantly associated with inferior allograft function. Since co-infection is strongly associated with acute rejection, co-infected individuals should be considered a risk collective.


[Soil strain of Bacillus subtilis harboring a large plasmid that mediates high-frequency conjugal mobilization].
The ability of a soil strain of Bacillus subtilis harboring a large plasmid, p19, to mobilize a small staphylococcus plasmid, pUB110, was studied. The latter plasmid was transferred to the recipient cells of Bacillus subtilis 168 at a high frequency (about 10(-2) per recipient cell) both on filter surface and in liquid medium. Mobilization was initiated 40 to 50 min after the beginning of the contact between donor and recipient cells.


[Recent advances in the treatment of myelodysplastic syndromes].
Myelodysplastic syndromes (MDS) are a group of clonal hematologic disorder, which combine ineffective hematopoiesis and evolution to acute myeloid leukemia. Significant progress has been made in the understanding of the disease pathogenesis, diagnostics and classification. Promising new agents and innovative therapeutic strategies are currently used. In this article we will review these achievements and their impact on the treatment of MDS. The pathogenesis of MDS involves abnormalities of the MDS clone itself such as abnormal apoptosis, signalling or epigenetic regulation and abnormalities of the microenvironment such as immune deregulation or increased angiogenesis, which represent potential therapeutic targets. There is currently no standard treatment for MDS and allogeneic stem cell transplantation remains the only curative strategy. However, besides conventional chemotherapy and growth factors, new agents including hypomethylating agents, antiangiogenic drugs, immune modulatory agents have proved effective. The interesting results achieved with these new agents show that it is necessary to continue investigation in order to improve therapeutic strategies in MDS.


Enhancing effects of binary mixtures of acid with salt on the gustatory neural activity in the clawed toad, Xenopus laevis.
Binary mixtures of acid with salt were observed to produce enhancing effects on oral chemoreceptor responses by recording the activity of the whole glossopharyngeal nerve of the clawed toad (Xenopus laevis). The mixtures of HCl with various inorganic salts elicited responses larger than the sum of the responses to individual component chemicals of each mixture. The results indicated that the mixture response was composed of a large HCI response and a negligibly small salt response. The concentration-response curve for HCl shifted toward lower concentrations due to the presence of NaCl without affecting the maximal response, and the Hill constant for the curve was unchanged, suggesting that the binding affinity of protons increases with an increase in the concentration of the mixed NaCl. The enhancing effects of the mixtures of HCl and various monovalent sodium salts having equal ionic strength showed distinct differences among the anion species of the salts. The responses to the mixtures of HCl with typical chloride salts having cations of various valencies depended on the Cl- ion concentration up to 0.1 M, whereas they depended on ionic strength as well, suggesting a possible role of salt cations in the enhancing effects of the mixtures. Thus, the enhancing effects of salts on the acid responses are interpreted mostly in terms of the interaction of the salt anions on the receptor membrane around the receptor sites for acid. The additive role of the cationic activity of the mixed salts, however, is also involved.


Refractory asthma phenotyping based on immunoglobulin E levels and eosinophilic counts: A real life study.
Asthma is an inflammatory heterogeneous disease with variable severity. The serum IgE level and Eosinophilic count have been used as biomarkers to define treatment strategies with biological agents in severe refractory asthma. The aim of this study is to determine the concurrence of high eosinophil count and elevated serum IgE levels in patients with severe refractory asthma. A retrospective cross-sectional real-life study was conducted on patients attending adult refractory asthma outpatient clinic between 2015 and 2018. Serum total IgE level and blood EOS count on matched dates with spirometry and Asthma Control Test (ACT) scores were collected. All data were obtained while patients were not on biological agents. A total of 142 patients with severe refractory asthma were included. The mean age was 43 years, mean eosinophilic count 564 cells/μL and mean serum IgE levels of 520 IU/ml. There was a significant correlation between serum IgE level and eosinophilic count. Serum IgE and eosinophilic count were concurrently elevated in 110 patients (78%). The patients were further categorized into four subgroups. Group A: IgE 30-100 IU/mL and EOS 150-300 cells/μL (7.3%), Group B: IgE >100 IU/mL and EOS 150-300 cells/μL (19.1%), Group C: IgE 30-100 IU/mL and EOS >300 cells/μL (14.5%) and Group D: IgE >100 IU/mL, EOS >300 cells/μL (59.1%). The majority of severe refractory asthma patients exhibits both elevated serum IgE level and eosinophilic counts.


An immunochemical method to measure atmospheric allergens.
Because particulate aeroallergens may exist in amorphous form as well as in pollen grains and fungal spores and because symptoms of allergic diseases presumably correlate with the total amount of allergen exposure, an immunochemical method of assay of aeroallergens would be useful. We report such a method based on (1) capture of airborne pollen, fungal spores, and amorphous particles 0.3 micrometer in diameter on fiberglass sheets with a high-volume air sampler; (2) elution of the sheets with buffered saline; and (3) analysis of eluate allergen content by radioallergosorbent test (RAST) inhibition assays. In preliminary indoor experiments we applied various quantities of short ragweed (SRW) pollen or dry Alternaria powder to the sheets while airflow was maintained at 1.19 m3/min. We compared techniques for extraction of allergen from the sheets, including homogenization, cutting and soaking, and descending elution of sheets. Although all three methods successfully extracted allergen from the sheets, an 8-hr descending elution procedure was optimal from the standpoint of yield and convenience. Eluates from filters exposed to as little as 4 mg of SRW pollen or Alternaria powder produced satisfactory RAST inhibition curves. When the sampler was operated outdoors continuously we could measure the atmospheric allergenic activity for both Alternaria and SRW from July to September. This allergenic activity was highly correlated with the traditional morphologic counts of airborne ragweed pollen and Alternaria spores.


Prevalence and risk factors of sexual dysfunction in patients with inflammatory bowel disease: systematic review and meta-analysis.
Sexual dysfunction (SD) is increasingly identified in patients with inflammatory bowel disease (IBD), but there are few systematic reviews and meta-analyses of the studies of SD in IBD patients. The purpose of the study is to further quantify the association between IBD and SD. MEDLINE (OVID), EMBASE (OVID), and the Cochrane Library (OVID) were searched (until August 2020) to identify observational studies that reported the prevalence and risk factors of SD in IBD patients. Pooled prevalence, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Of the 945 citations evaluated, 18 studies (including 36,676 subjects) reporting the prevalence of SD in the IBD population were included for analysis. The overall pooled prevalence was 39% (95% CI 37-40%, P < 0.001). The prevalence of SD in women was 53% (95% CI 50-55%, P < 0.001), and it was 27% (95% CI 25-29%, P < 0.001) in men. The prevalence was higher in conjunction with operation (OR, 1.33, 95% CI 1.22-1.45, P < 0.001), depression (OR 6.14, 95% CI 3.51-10.76, P < 0.001), disease activity (OR 2.73, 95% CI 1.32-5.64, P = 0.007), comorbidities (OR 3.21, 95% CI 2.06-5.00, P < 0.001), age < 50 years (OR 3.85, 95% CI 2.41-6.14, P < 0.001), and the need for corticosteroids (OR 2.62, 95% CI 1.48-4.66, P = 0.001). SD occurred frequently in the IBD population. Operation, depression, disease activity, comorbidities, age < 50 years, and the need for corticosteroids were risk factors for SD in IBD patients. SD screening might be recommended in IBD patients with the aforementioned factors.


Monitoring the mechanism of anti-cancer agents to inhibit colorectal cancer cell proliferation: Enzymatic biosensing of glucose combined with molecular docking.
Glucose, a major energy source in cellular metabolism, has a significant role in cell growth. The increase in glucose uptake is a distinguishing hallmark in cancer cells. A key step in glucose utilization is the transport of glucose to the cancer cells for supplying their additional energy. The glucose transporter (or GLUT) family is a membrane protein which facilitates the uptake of glucose in most cancer cell types. Given the increased glucose level in cancer cells and the regulatory role of GLUTs in glucose uptake, it is required to combine both experimental and theoretical studies to develop new methods to monitor cell proliferation. Herein, for the first time, a new strategy was proposed to evaluate the cell proliferation of HT-29 based on glucose consumption in the presence of resveratrol (RSV) as an anticancer agent. A hybrid nanocomposite of carbon nanofibers and nitrogen-doped graphene quantum dots was used to design an enzymatic sensor for the selective and sensitive determination of glucose in cancer cells. The results obtained from the voltammetric technique were compared with the conventional colorimetric assay. A good correlation was observed between the proliferation rate and glucose utilization by cancer cells. As it was observed, RSV induces a decrease in glucose consumption, indicating lower glucose uptake efficiency for HT-29 cells. Molecular docking studies reveal that RSV can block the interaction of glucose with the GLUT family. This is one of the possible mechanisms for the decrease of glucose level followed by the reduction of cell proliferation in the presence of RSV. Compared with traditional methods, in vitro electrochemical techniques benefit from simple, nontoxic, sensitive and low-cost detection assays and hence serve as a novel tool to pursue the growth inhibition of cancer cell in response to anti-cancer agents.


Hepatocytes in suspension.
Isolated hepatocytes are a physiologically relevant in vitro model exhibiting intact subcellular organelles, xenobiotic transport, and integrated phase I and phase II biotransformation. They represent the "gold standard" for investigating xenobiotic biotransformation and metabolic bioactivation. When used in suspension, they provide an easy-to-handle and relatively cheap in vitro system that can be used for up to 4 h. The use of animal- and human-derived hepatocytes allows interspecies comparisons of metabolic properties. In contrast with microsomes, which are easily prepared from human liver tissue and can be stored in liquid nitrogen with minimal loss of functionality, cryopreservation of isolated human hepatocytes has been shown to be more difficult: after thawing losses of cell viability and biotransformation capacity occur. We provide general recommendations for the appropriate use of hepatocytes in suspension for pharmaco-toxicological studies. We also provide protocols for the cryopreservation of freshly isolated hepatocytes and their handling on thawing.


PFASs: What can we learn from the European Human Biomonitoring Initiative HBM4EU.
Per- and polyfluoroalkyl substances (PFASs) were one of the priority substance groups selected which have been investigated under the ambitious European Joint programme HBM4EU (2017-2022). In order to answer policy relevant questions concerning exposure and health effects of PFASs in Europe several activities were developed under HBM4EU namely i) synthesis of HBM data generated in Europe prior to HBM4EU by developing new platforms, ii) development of a Quality Assurance/Quality Control Program covering 12 biomarkers of PFASs, iii) aligned and harmonized human biomonitoring studies of PFASs. In addition, some cohort studies (on mother-child exposure, occupational exposure to hexavalent chromium) were initiated, and literature researches on risk assessment of mixtures of PFAS, health effects and effect biomarkers were performed. The HBM4EU Aligned Studies have generated internal exposure reference levels for 12 PFASs in 1957 European teenagers aged 12-18 years. The results showed that serum levels of 14.3% of the teenagers exceeded 6.9 μg/L PFASs, which corresponds to the EFSA guideline value for a tolerable weekly intake (TWI) of 4.4 ng/kg for some of the investigated PFASs (PFOA, PFOS, PFNA and PFHxS). In Northern and Western Europe, 24% of teenagers exceeded this level. The most relevant sources of exposure identified were drinking water and some foods (fish, eggs, offal and locally produced foods). HBM4EU occupational studies also revealed very high levels of PFASs exposure in workers (P95: 192 μg/L in chrome plating facilities), highlighting the importance of monitoring PFASs exposure in specific workplaces. In addition, environmental contaminated hotspots causing high exposure to the population were identified. In conclusion, the frequent and high PFASs exposure evidenced by HBM4EU strongly suggests the need to take all possible measures to prevent further contamination of the European population, in addition to adopting remediation measures in hotspot areas, to protect human health and the environment. HBM4EU findings also support the restriction of the whole group of PFASs. Further, research and definition for additional toxicological dose-effect relationship values for more PFASs compounds is needed.


Dynamic footprints: adjuvant method for postoperative assessment of patients after calcaneal fractures.
Open reduction and internal fixation are the current trends of treatment for comminuted calcaneal fractures. Assessing treatment results is often difficult due to discrepancy between objective parameters such as range of movement, and subjective results such as pain. To test the reliability of footprint analysis as an adjuvant method of postoperative assessment of patients who sustained calcaneal fractures. Dynamic and static footprint analysis was used as an adjuvant additional method to objectively assess operative results. This method is simple and is independent of the patient's initiatives. This modality was used in 22 patients followed-up 9-90 months postoperatively. We found a good correlation between footprint analysis and objective and subjective parameters of results expressed by American Orthopedic Foot and Ankle Society hind foot score. In certain cases, this method can be used to distinguish between uncorrelated parameter results, such as malingering, and workmens' compensation claims. We recommend the use of this simple, non-invasive objective test as an additional method to assess the results of ankle and foot surgery treatment.


Ethnic-minority groups in England and Wales-factors associated with the size and timing of elevated COVID-19 mortality: a retrospective cohort study linking census and death records.
We estimated population-level associations between ethnicity and coronavirus disease 2019 (COVID-19) mortality using a newly linked census-based data set and investigated how ethnicity-specific mortality risk evolved during the pandemic. We conducted a retrospective cohort study of respondents to the 2011 Census of England and Wales in private households, linked to death registrations and adjusted for emigration (n = 47 872 412). The outcome of interest was death involving COVID-19 between 2 March 2020 and 15 May 2020. We estimated hazard ratios (HRs) for ethnic-minority groups compared with the White population, controlling for individual, household and area characteristics. HRs were estimated on the full outcome period and separately for pre- and post-lockdown periods. In age-adjusted models, people from all ethnic-minority groups were at elevated risk of COVID-19 mortality; the HRs for Black males and females were 3.13 (95% confidence interval: 2.93 to 3.34) and 2.40 (2.20 to 2.61), respectively. However, in fully adjusted models for females, the HRs were close to unity for all ethnic groups except Black [1.29 (1.18 to 1.42)]. For males, the mortality risk remained elevated for the Black [1.76 (1.63 to 1.90)], Bangladeshi/Pakistani [1.35 (1.21 to 1.49)] and Indian [1.30 (1.19 to 1.43)] groups. The HRs decreased after lockdown for all ethnic groups, particularly Black and Bangladeshi/Pakistani females. Differences in COVID-19 mortality between ethnic groups were largely attenuated by geographical and socio-demographic factors, though some residual differences remained. Lockdown was associated with reductions in excess mortality risk in ethnic-minority populations, which has implications for a second wave of infection.