A protocol for randomized controlled trial on multidisciplinary interventions for mobility limitation in the older adults (M-MobiLE).
Mobility limitation-the loss of exercise capacity or independent living ability-is a common geriatric syndrome in older adults. As a potentially reversible precursor to disability, mobility limitation is influenced by various factors. Moreover, its complex physiological mechanism hinders good therapeutic outcomes with a single-factor intervention. Most hospitals have not incorporated the diagnosis and evaluation of mobility limitation into medical routines nor developed a multidisciplinary team (MDT) treatment plan. We aim to conduct a clinical trial titled "A Multidisciplinary-team approach for management of Mobility Limitation in Elderly (M-MobiLE)" to explore the effect of the MDT decision-making intervention for mobility limitation. The M-MobiLE study will be a multicenter, randomized, and controlled trial. We will recruit a minimum of 66 older inpatients with mobility limitation from at least five hospitals. Older patients with mobility limitation admitted to the geriatrics department will be included. Short-Physical Performance Battery (SPPB), Activities of Daily Living (ADL), Function Impairment Screening Tool (FIST), Geriatric Depression Scale (GDS-15), Short Form - 12 (SF-12), Fried frailty phenotype, social frailty, Morse Fall Risk Scale, SARC-CalF, Mini-Mental State Examination (MMSE), Mini-Nutritional Assessment Short-Form (MNA-SF), and intrinsic capacity will be assessed. The intervention group will receive an exercise-centered individualized MDT treatment, including exercise, educational, nutritional, medical, and comorbidity interventions; the control group will receive standard medical treatment. The primary outcome is the change in the SPPB score, and the secondary outcomes include increased SF-12, ADL, FIST, MMSE, MNA-SF, and intrinsic capacity scores and decreased GDS-15 and SARC-CalF scores. Our results will help develop a multidisciplinary decision-making clinical pathway for inpatients with mobility limitation, which can be used to identify patients with mobility limitation more effectively, improve mobility, and reduce the risk of falls, frailty, and death in older inpatients. The implementation of this MDT strategy may standardize the treatment of mobility limitation, reduce adverse prognosis, and improve quality of life. ChiCTR, ChiCTR2200056756, Registered 19 February 2022.


Quantitative profiling of retinyl esters in milk from different ruminant species by using high performance liquid chromatography-diode array detection-tandem mass spectrometry.
An effective high performance liquid chromatography-diode array detection-tandem mass spectrometry (HPLC-DAD-MS/MS) analytical approach was developed for retinoid profiling in raw milk samples (cow, buffalo, ewe, and goat). The analytes were isolated by means of liquid-liquid extraction, including a "lipid freezing" step, with yields exceeding 66%. Since the positive atmospheric pressure chemical ionisation mass spectrometry (APCI-MS) detection is not completely selective, a reliable identification has been accomplished by fully separating the analytes on a tandem C18/C30 column system under non-aqueous reversed phase (NARP) chromatography conditions. After validation, different milk varieties obtained from pasture-fed animals were analysed, providing, for the first time, the retinoid composition of both buffalo's and ewe's milk. According to the literature, retinyl palmitate has been found to be the most abundant vitamin A vitamer, but retinyl oleate is the prevalent form in the caprine milk.


The feasibility, efficacy and functional outcome of local anaesthetic repair of anterior and posterior vaginal wall prolapse.
Urogenital prolapse is a very common condition in women with a prevalence of 30%. If conservative therapy fails or is not desired by the patient, prolapse repair is usually performed under general or regional anaesthetic. The aim of the study was to evaluate feasibility, efficacy and functional outcome after fascial prolapse repairs under local anaesthetic (LA). Between November 1999 and December 2000, 130 consecutive patients presenting with anterior or posterior prolapse or both were invited to have their procedure performed under LA. All patients with a symptomatic minimum stage II prolapse were included. Prior to surgery all women completed a standardized questionnaire examining the specific and non-specific symptoms of prolapse and their situation was classified using the ICS Pelvic Organ Prolapse (POP-Q) system. Follow up was 30 months. Objective success was defined as a stage 1 or less and no symptoms of bulge, subjective success was defined as lack of specific or non-specific symptoms of prolapse. There were 128 patients who agreed to have their operations performed under LA: 68 in the anterior group, 52 in the posterior group and 8 with a combined anterior and posterior repair. Objective cure rate was 88% for posterior repair, 87% for anterior repair and 63% for combined repair. Success rates were no different in primary from recurrent cases. There were no intraoperative complications and operating time was 21 min (anterior repair) or 23 min (posterior repair). There was no de novo postoperative urinary or stool incontinence and all patients but two would have the operation performed again under the same circumstances. The two remaining refused due to embarrassment but for no other reason. Local anaesthetic prolapse repair is feasible and effective in middle term results. It is well accepted by the patients who benefit from less side effects and short hospital stay.


Stimuli-responsive composite hydrogels with three-dimensional stability prepared using oxidized cellulose nanofibers and chitosan.
Stimuli-responsive hydrogels have garnered the attention of the hydrogel industry, as they are able to change their physical and chemical properties based on changing external stimuli such as pH, temperature, ionic strength, electromagnetic fields, and light. However, stimuli-responsive hydrogel applications are hindered due to their inevitable swelling and shrinkage. Bacterial cellulose (BC), a natural hydrogel with tightly packed cellulose nanofibers (CNFs) was oxidized into dialdehyde BC (DABC) and was composited with chitosan (CS), a readily available natural polymer, to develop a mechanically adaptive hydrogel composite under different pH conditions. Composites exhibit pH sensitivity by presenting higher mechanical properties under acidic conditions and lower mechanical properties under basic conditions owing to the protonation of amino groups of the chitosan chains. Osmotic pressure is built up under acidic conditions, increasing the mechanical strength of the composites. The good three-dimensional stability of composites enables them to consistently maintain their volume when exposed to acidic or basic conditions.


Selenium and Methionine Sulfoxide Reduction.
Selenium is an essential trace element because it is present in proteins in the form of selenocysteine residue. Functionally characterized selenoproteins are oxidoreductases. Selenoprotein methionine-R-sulfoxide reductase B1 (MsrB1) is a repair enzyme that reduces ROS-oxidized methionine residues in proteins. Here, we explored a possibility that reversible methionine oxidation is also a mechanism that regulates protein function. We found that MsrB1, together with Mical proteins, regulated mammalian actin assembly via stereospecific methionine oxidation and reduction in a reversible, site-specific manner. Two methionine residues in actin were specifically converted to methionine-R-sulfoxide by Mical1 and Mical2 and reduced back to methionine by MsrB1, supporting actin disassembly and assembly, respectively. Macrophages utilized this redox control during cellular activation by stimulating MsrB1 expression and activity. Thus, we identified the regulatory role of MsrB1 as a Mical antagonist in orchestrating actin dynamics and macrophage function. More generally, our study showed that proteins can be regulated by reversible site-specific methionine-R-sulfoxidation and that selenium is involved in this regulation by being a catalytic component of MsrB1.


Neuropeptide Y immunoreactivity in the locus coeruleus of the rat brain.
The detailed distribution of neuropeptide Y immunoreactive neurons and fibres is given for the rat locus coeruleus. The studies were carried out using indirect immunofluorescence and avidin-biotin-peroxidase techniques. It was shown that in colchicine pretreated rats, about 15-20% of locus coeruleus neurons contain neuropeptide Y immunoreactivity. Neuropeptide Y immunoreactive neurons form two populations: (1) medium-sized or large neurons, poorly immunostained, situated mainly in the dorsal and central locus coeruleus nucleus, and (2) small, strongly immunostained neurons in ventromedial parts of the nucleus. Neuropeptide Y immunoreactive fibres and terminals are scattered throughout the locus coeruleus, but are more numerous in its ventromedial and ventrorostral parts.


The autumn low milk yield syndrome in Brown Swiss cows in continental climates: hypotheses and facts.
Extensive research has been conducted globally on the impact of heat stress (HS) on animal health and milk production in dairy cows. In this article, we examine the possible reasons for the decrease in milk production in Brown Swiss (BS) cows during the autumn season, known as the autumn low milk yield syndrome (ALMYS). This condition has been extensively studied in high-yielding Holstein Friesian (HF) cattle and has also been observed in BS cows with a daily milk yield of around 30 kg. Our hypothesis is that the drop in milk yield and the increased prevalence of mastitis in autumn, as found in our recent studies, may be a long-term consequence of summer HS. We re-evaluate our previous findings in light of the possible manifestation of an HS-related form of ALMYS in BS cows. As milk yield, mastitis spread, and reproductive function of cows are interrelated and have seasonal dependence, we examine the consistency of our hypothesis with existing data. The significant drop in milk yield in BS cows in autumn (by 2.0-3.2 kg), as well as the threshold of milk yield decrease (temperature-humidity index of 70.7), may point in favour of the manifestation of ALMYS in BS cows, similar to HF cows. Only the percentage effect of seasonal factor (59.4%; p < 0.05) on milk yield of BS cows was significant. HS-related ALMYS provides a robust conceptual framework for diverse sets of productive and animal health data in BS cows, similar to observations in high-yielding HF cattle. However, the limitations associated with the lack of additional data (e.g. immunological indicators) suggest the need for further research to confirm ALMYS in BS breed.


Recurrent appendicitis: reexamination of a controversial disease.
The existence of recurrent appendicitis as a true disease entity is still disputed. The controversy surrounding recurrent appendicitis is discussed. This disease is thought to represent repeated inflammation of a nonperforated appendix. Case material supporting this concept is presented. The barium enema can provide evidence of the diseased appendix.


A new take on prions: preventing Alzheimer's disease.
Alzheimer's disease is a major neurodegenerative disease of the brain, the incidence of which increases dramatically in old age. Currently, no drugs are available to halt or slow the progression of this disease, which poses an ever-expanding burden on health services, families and society. The prion protein has become infamous owing to its role as the causative agent of the transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease in humans. However, our view of the prion protein as an unwanted, harmful entity has been challenged recently. New data indicate that the normal cellular form of the prion protein might have a crucial role in suppressing the production of the amyloid-beta peptide, the neurotoxic molecule involved in the pathogenesis of Alzheimer's disease.


Is urinary soluble Fas an independent predictor of non-muscle-invasive bladder cancer? A prospective chart study.
To evaluate whether soluble Fas (sFas) in urine is an independent predictor of non-muscle-invasive bladder cancer (NMIBC). We performed a prospective chart review which included 128 subjects with NMIBC and 88 controls. The first morning voided urine sample (10-20 ml) was obtained from preoperative patients and controls. Expression levels of sFas in urine were analyzed using enzyme-linked immunosorbent assay. Clinical and pathological data, European Organisation for Research and Treatment of Cancer (EORTC) risk group category, follow-up data and urinary sFas values were gathered from each patient, and each prognostic outcome was evaluated. sFas levels were significantly higher in the urine of patients with NMIBC than of those without NMIBC (p = 0.000). The level was significantly higher in cases with a higher stage or grade or high-risk and recurrent disease than in those with a lower stage or grade or low-risk and nonrecurrent disease (each p < 0.05). Kaplan-Meier estimates revealed a significant difference in time to recurrence based on sFas levels in the urine of the NMIBC patients (log-rank test; p = 0.000). On multivariate Cox regression analysis, EORTC risk group category (hazards ratio [HR] = 3.250, p = 0.000) and urinary sFas level (HR = 1.403, p = 0.015) were the independent predictors of NMIBC recurrence. Our study indicated that urinary sFas assay results may help identify NMIBC patients at risk of tumor recurrence. These data can be used to design a future follow-up schedule and treatment strategy for NMIBC patients.


Isolation and characterization of SARS-CoV-2 Beta variant from UAE travelers.
The emergence of SARS-CoV-2 variants in places where the virus is uncontained poses a global threat from the perspective of public health and vaccine efficacy. Travel has been important factor for the easy spread of SARS-CoV-2 variants worldwide. India has also observed the importation of SARS-CoV-2 variants through international travelers. In this study, we have collected the oropharyngeal and nasopharyngeal swab specimens from 58 individuals with travel history from United Arab Emirates (UAE), East, West and South Africa, Qatar, Ukraine and Saudi Arabia arrived in India during February-March 2021. The clinical specimens were initially screened for SARS-CoV-2 using Real time RT-PCR. All the specimens were inoculated on to Vero CCL-81 cells for virus isolation. The viral isolates were further sequenced using Next-Generation Sequencing. All 58 cases were tested positive for SARS-CoV-2 using Real time RT-PCR. Four specimens showed progressive infectivity with fusion of the infected cells with neighboring cells leading to large mass of cells. Replication competent virus was confirmed from culture supernatant of the passage 2 using Real time RT-PCR. Two plaque purified SARS-CoV-2 isolates demonstrated high viral RNA load of 3.8-7.5 × 1011 and 1.1-1.6 × 1011 at passage 4 and 5 respectively. Nucleotide variations along with amino acid changes were also observed among these two isolates at passage 2-5. All four cases were male with no symptoms and co-morbidity. The sequence analysis has shown two different clusters, first cluster with nucleotide deletions in the ORF1ab and the spike, while second cluster with deletions in spike region. The viral isolates demonstrated 99.88-99.96% nucleotide identity with the representative sequences of Beta variant (B.1.351). These findings suggest easier transmission of SARS-CoV-2 variants with human mobility through international travel. The isolated Beta variant would be useful to determine the protective efficacy of the currently available and upcoming COVID-19 vaccines in India.


Combination therapy with flutamide and castration (LHRH agonist or orchiectomy) in previously untreated patients with clinical stage D2 prostate cancer: today's therapy of choice.
One hundred and ninety-nine patients with clinical stage D2 prostate cancer who had not received previous endocrine therapy or chemotherapy were treated with the combination therapy using the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average of 26 months (3-59 months). The objective response to the treatment was assessed according to the criteria of the U.S. NPCP. There was a 5.7-fold increase (26.3 vs 4.6%) in the percentage of patients who achieved a complete response compared with the results obtained in five recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 12 of the 186 evaluable patients (6.5%) did not show an objective positive response at the start of the combination therapy compared with an average of 18% in the same five studies using monotherapy. The duration of response was also significantly improved in the patients who received the combination therapy while the death rate was decreased by approximately two-fold during the first 4 yr of treatment. In fact, while an approximately 50% death rate is observed at 2 yr in all studies using monotherapy, the same 50% death rate is delayed by 2 yr in the present study. It should be mentioned that at the time of relapse under combination therapy, the treatment is continued and, in addition, further blockade of adrenal androgen secretion is achieved with aminoglutethimide. The marked (5.7-fold) improvement in the rate of complete objective responses coupled with the three-fold decrease in the number of non-responders, the increased duration of the positive responses and the two-fold decrease in the death rate during the first 4 yr of treatment are obtained with the combination therapy using Flutamide and castration, thus improving the quality and duration of life with no or minimal side-effects. By blocking the androgen receptors in the prostatic cancer tissue, the antiandrogen decreases the action of the androgens of adrenal origin and thus inhibits the growth of a large number of tumors which, otherwise, would continue to be stimulated by the adrenal androgens left after medical or surgical castration.


Theoretical study on the mechanisms of the decomposition of nitrate esters and the stabilization of aromatic amines.
The nitrate esters are important components of double-base propellants. Aromatic amines are recommended as the stabilizers to delay the decomposition of nitrate esters and increase their storage time. The decomposition mechanisms of alkyl, alkoxy dinitrate, and poly-fluoride nitrate esters and the stabilizing effect of aromatic amines including new designed phenols are studied at the level of B3LYP/6-31G**. Alkyl and alkoxyl dinitrate esters are likely to be transformed by hydrogen abstraction, which is consistent with that of mononitrate and trinitrate esters. However, for poly-fluoride nitrate esters, NO2 catalyzed self-decomposition is preferred. In addition, comparing with mononitrate and trinitrate esters, the order of their stability is mononitrates > dinitrates > trinitrates. Poly-fluoride nitrate esters have a poorer stability than non-fluorinated nitrate esters. Comparing with parent nitrate esters, the stability of new designed poly-fluoride oxygen-containing nitrate esters is slightly improved. Aromatic amines including new designed phenols are effective stabilizers of nitrate esters, especially when introduced hydroxyl in the para position, can enhance the effects of stabilizers. The rate constants for the decomposition of nitrate esters and the bimolecular reaction between stabilizers and NO2 are calculated by using traditional transition state theory. Graphical abstractComparison between the reaction energy barrier of nitrate esters and stabilizers with NO2.


Resetting of tachycardia cycle by single and double ventricular extrastimuli in recurrent sustained ventricular tachycardia.
In two cases with recurrent sustained ventricular tachycardia (VT) due to re-entry, the response pattern to extrastimuli during the tachycardia was studied. In each case, right ventricular extrastimuli with longer coupling intervals during VT were followed by fully compensatory pauses and with shorter coupling intervals reset the tachycardia cycle. In one case, a plateau was produced by a single extrastimulus, resembling that seen in the response curve of sinus node automaticity as well as ectopic atrial tachycardia. Two successive stimuli produced three definite zones, i.e., fully compensatory, reset producing a plateau, and progressive prolongation zones with shortening of the coupling intervals between the two stimuli, and terminated the tachycardia with further shortening of the coupling intervals. In conclusion, resetting phenomenon was confirmed on two cases with re-entrant VT. This phenomenon cannot be used as a criterion to determine the mechanism responsible for VT.


Improved fractional order speed controller with non-linear VSI-IM model to enhance the load disturbance capability.
The conventional PI-based speed controllers are susceptible to speed tracking error and limited load rejection capability. This paper presents the high-performance fractional-order PI speed controller (FOPI) for field oriented control of induction motor (FOC-IM) drives with enhanced disturbance rejection capability. The design of FOPI involves third-order voltage source inverter fed induction motor (VSI-IM) model identification, fitting it into the required phase margin and gain margin constraints and Oustaloups fractional element approximation. The identification algorithm using the hardware-in-loop system is provided. The non-linear integer order VSI-IM model improves the tracking and dynamic performance of the drive. The designed FOPI speed controller performance is compared with the literature's existing FOPI controller design methods. The experimental analysis found that, in terms of speed tracking, parameter variations, inertia variations, and disturbance rejection capabilities, the suggested controller is more effective and resilient than existing tuning approaches.


The involvement of cell death and survival in neural tube defects: a distinct role for apoptosis and autophagy?
Neural tube defects (NTDs), such as spina bifida (SB) or exencephaly, are common congenital malformations leading to infant mortality or severe disability. The etiology of NTDs is multifactorial with a strong genetic component. More than 70 NTD mouse models have been reported, suggesting the involvement of distinct pathogenetic mechanisms, including faulty cell death regulation. In this review, we focus on the contribution of functional genomics in elucidating the role of apoptosis and autophagy genes in neurodevelopment. On the basis of compared phenotypical analysis, here we discuss the relative importance of a tuned control of both apoptosome-mediated cell death and basal autophagy for regulating the correct morphogenesis and cell number in developing central nervous system (CNS). The pharmacological modulation of genes involved in these processes may thus represent a novel strategy for interfering with the occurrence of NTDs.


Acute lithium administration selectively lowers tyrosine levels in serum and brain.
Lithium exerts anti-dopaminergic behavioral effects. We examined whether some of these might be mediated by changes in brain levels of tyrosine (TYR), the precursor to dopamine. Lithium chloride (LiCl(2)) 3.0mEq/kg IP acutely lowered serum TYR and the ratio of serum TYR to other large neutral amino acids (LNAAs); it also selectively lowered striatum TYR levels as measured in tissue or in vivo. While LiCl(2) 3.0mEq/kg IP also augmented haloperidol (0.19mg/kg SC)-induced catalepsy, this lithium effect was not attenuated by administration of TYR 100mg/kg IP. We conclude that lithium acutely and selectively lowers brain TYR by lowering serum levels of tyrosine relative to the LNAAs that compete with it for transport across the blood-brain barrier. However, the lowering of TYR does not appear to significantly contribute to the ability of lithium to potentiate haloperidol-mediated catalepsy.


Pacemaker Implants and Their Influence on the Daily Life of Patients with Dementia with Lewy Bodies: A Qualitative Case Study.
Dementia with Lewy bodies (DLB) is an incurable form of dementia associated with detriments to the daily life of patients and carers from their family. Symptoms of orthostatic hypotension, syncope, and falls are supportive of DLB diagnosis. These symptoms may also be present among people with sick sinus syndrome (SSS), and subsequent pacemaker treatment to manage bradyarrhythmia is associated with improved cognitive function. The prevalence of SSS seems to be higher among people with underlying Lewy body pathology compared to the general age-matched population (5.2% vs. 0.17%). To our knowledge, how people with DLB and their family carers may experience pacemaker treatment to manage bradyarrhythmia has not been previously reported. Therefore, the aim of this study was to explore how people with DLB experience daily life following a pacemaker implant to manage associated symptoms of bradyarrhythmia. A qualitative case study design was used. Two men with DLB and their spouse carers were repeatedly interviewed as a dyad within 1 year following implant of a dual-chamber rate-adaptive (DDD-CLS) pacemaker to manage SSS in the men. Content analysis was used to assess the qualitative interview data collected. Three categories emerged: (1) gaining control, (2) maintaining a social life, and (3) being influenced by concurrent diseases. Less syncope/falls and remote pacemaker monitoring increased a sense of control in everyday life, while perceived physical and/or cognitive improvements influenced social participation. The men were still affected by concurrent diseases, which continuously influenced each couple's daily life. Identifying and managing concurrent bradyarrhythmia through a pacemaker implant could improve well-being for people with DLB.


Latest Advances in the Use of Therapeutic Focused Ultrasound in the Treatment of Pancreatic Cancer.
Traditional oncological interventions have failed to improve survival for pancreatic cancer patients significantly. Novel treatment modalities able to release cancer-specific antigens, render immunologically "cold" pancreatic tumours "hot" and disrupt or reprogram the pancreatic tumour microenvironment are thus urgently needed. Therapeutic focused ultrasound exerts thermal and mechanical effects on tissue, killing cancer cells and inducing an anti-cancer immune response. The most important advances in therapeutic focused ultrasound use for initiation and augmentation of the cancer immunity cycle against pancreatic cancer are described. We provide a comprehensive review of the use of therapeutic focused ultrasound for the treatment of pancreatic cancer patients and describe recent studies that have shown an ultrasound-induced anti-cancer immune response in several tumour models. Published studies that have investigated the immunological effects of therapeutic focused ultrasound in pancreatic cancer are described. This article shows that therapeutic focused ultrasound has been deemed to be a safe technique for treating pancreatic cancer patients, providing pain relief and improving survival rates in pancreatic cancer patients. Promotion of an immune response in the clinic and sensitisation of tumours to the effects of immunotherapy in preclinical models of pancreatic cancer is shown, making it a promising candidate for use in the clinic.


Identifying differentially expressed genes in meta-analysis via Bayesian model-based clustering.
A Bayesian model-based clustering approach is proposed for identifying differentially expressed genes in meta-analysis. A Bayesian hierarchical model is used as a scientific tool for combining information from different studies, and a mixture prior is used to separate differentially expressed genes from non-differentially expressed genes. Posterior estimation of the parameters and missing observations are done by using a simple Markov chain Monte Carlo method. From the estimated mixture model, useful measure of significance of a test such as the Bayesian false discovery rate (FDR), the local FDR (Efron et al., 2001), and the integration-driven discovery rate (IDR; Choi et al., 2003) can be easily computed. The model-based approach is also compared with commonly used permutation methods, and it is shown that the model-based approach is superior to the permutation methods when there are excessive under-expressed genes compared to over-expressed genes or vice versa. The proposed method is applied to four publicly available prostate cancer gene expression data sets and simulated data sets.


[Bonded porcelain laminates--an alternative to anterior porcelain crowns].
The trend towards esthetic dentistry, which originates in the USA, has added new dimensions to the treatment of anterior teeth. One of it is the porcelain laminate technique. Using composites, extremely thin, manually prepared porcelain laminates with a thickness of 0.3 to 0.5 mm are bounded to the labial aspect of front teeth or laterals. On account of the low laminate thickness very little enamel preparation is needed. The residual enamel mass and the translucency of the ceramic material produce a natural appearance and optimal cosmetic results. This technique enables the dentist to restore the shape and color of esthetically compromised teeth.


Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes.
In the past decade, C4d has emerged as a potential marker for antibody-mediated rejection (AMR); however, evidence on its use as a prognostic tool has been controversial. Although the International Society for Heart and Lung Transplantation guideline recommends early routine surveillance of C4d in heart transplantation, there is no consensus on its value in the pathologic assessment of AMR. Herein we present a correlation analysis of C4d immunoreactivity in endomyocardial biopsies with clinical cardiac dysfunction, cellular rejection, human leukocyte antigen (HLA) status, cardiac allograft vasculopathy (CAV) and death. A total of 5,840 endomyocardial biopsies from 296 heart transplant recipients (January 2004 to December 2014) were stained prospectively for C4d. Strong, diffuse endothelial staining was considered positive. All patients had at least 1 year of follow-up. Positive C4d staining was present in 53 biopsies from 28 patients. Sixteen of 28 patients had clinically significant cardiac dysfunction at the time of positive biopsy. In C4d-positive patients, the mean panel-reactive antibody (PRA) level was 33%. Ten patients demonstrated a first C4d positivity within the first year post-transplant, whereas 18 patients had C4d positivity after 1 year post-transplant. At autopsy, all 11 C4d-positive patients examined demonstrated cardiac allograft vasculopathy (CAV) as the underlying cause of death. In contrast, only 2 of 8 (25%) C4d-negative patients had CAV at autopsy. In the surviving cohort, there was an angiographic diagnosis of higher-than-moderate CAV in 10 patients (3.8%). C4d-positive patients contributed to 67% of the overall institutional mortality in heart transplant recipients. Late C4d positivity (>1 year post-transplant) demonstrated an even higher risk for developing CAV and poor prognosis than early C4d positivity (within 1 year). In the C4d-negative group with postmortem examination, 75% (6 of 8) deaths were due to non-cardiac causes. Our findings show a positive association of C4d with CAV and death. We identified a prognostic role for C4d in heart transplantation warranting routine long-term detection of this marker in the pathologic evaluation of cardiac AMR.


The frequency of radiology reporting of childhood obesity.
The purpose of our study was to review the current practice of radiologists with respect to dictating the presence of obesity in imaging reports. Over 1 million radiology reports dictated at a large pediatric hospital from 1994 to 2002 were analyzed for several keywords relating to obesity. The number of cases in which the keywords appeared was recorded for each year, and a percentage was calculated. Reports done in 1999 and 2000 were further analyzed to determine where the keywords were positioned within the report. The number of reports containing a keyword ranged from 131 to 456 per year. During each year, documentation of obesity occurred in less than 0.4% of all reports. During that same time period, the national prevalence of pediatric obesity ranged from 6-16%. Detailed examination of the 1999 and 2000 reports showed that even in the reports that mentioned obesity, it was usually not listed in the diagnostic impression. Despite the increase in public awareness of obesity and increasing recognition of obesity-related disease, this study did not find a similar awareness among radiologists at a large pediatric radiology department. The reason for this discrepancy is speculative and likely multifactorial. Regardless, radiologists may be missing an opportunity to play a role in disease prevention and early recognition by documenting findings of obesity and thereby bringing them to the attention of referring physicians.


Importance of 1,25-dihydroxyvitamin D3 and the nonadherent cells of marrow for osteoblast differentiation from rat marrow stromal cells.
Although steroid hormones regulate mature osteoblast function, much less is known about their actions on osteoprogenitor cells. The possibility of steroid hormone regulation of early stages in osteoblast differentiation was investigated by measuring the growth and induction of the osteoblast marker enzyme alkaline phosphatase (AP) in rat bone marrow stromal cell cultures. Experiments were performed in charcoal-stripped serum; conditions which markedly impaired stromal cell growth. However, growth could be stimulated by nonadherent marrow cell-derived conditioned medium. 1,25(OH)2D3, but not dexamethasone, 17 beta-estradiol, or retinoic acid, increased both stromal cell proliferation and AP activity. The increased proliferation with 1,25(OH)2D3 was nonadherent cell-dependent. BMP-2 also increased AP levels and acted in synergy with 1,25(OH)2D3. These results suggest that (i) nonadherent marrow cells may support stromal cell development, and (ii) 1,25(OH)2D3 as well as glucocorticoids may regulate osteogenesis from the bone marrow but a similar role for estrogen is not supported.


Chronic infection with Trypanosoma musculi in congenitally athymic nude mice.
Trypanosoma musculi produces a chronic infection with a consistently elevated parasitemia in nude mice. Thymic reconstitution of nude mice restores immunity to the infection.


Too fat to exercise? Obesity as a barrier to physical activity.
To describe perceptions of being 'too fat' as a barrier to physical activity by gender and body mass index, and to examine the associations between feeling fat and other weight-related barriers to physical activity. Analyses of cross-sectional self-report data from a representative population survey of 2,298 Australian adults. Overall, 4.4% of respondents reported being too fat as a barrier to physical activity; this being more common among women (6.2%), and among the obese (22.6%). Associations were found between being too fat as a barrier, and being too shy or embarrassed to exercise; being too lazy or not motivated; having an injury or disability (males only); and being not the sporty type (females only). There was no association between feeling too fat and poor health. Feeling too fat to exercise is a common barrier among the overweight, particularly for women. Results suggest gender differences in weight-related barriers to physical activity. A better understanding of the nature of weight-related physical activity barriers can help inform public health strategies designed to increase physical activity among those who are obese.


Endothelium-independent potentiating effects of neuropeptide Y in the rat tail artery.
The role of the endothelium in the potentiating action of neuropeptide Y (NPY) to contraction induced by KCl, alpha, beta-methylene ATP (mATP), and noradrenaline (NA) was tested on rat tail arteries. Endothelium-intact and denuded ring segments and freshly isolated single smooth muscle cells were used in the study. Contraction responses to KCl and mATP were potentiated by NPY (50 nM) in both intact and denuded arteries. Contraction to NA was potentiated by NPY at 500 nM but not at 50 nM. The potentiation effect of NPY was antagonized by nifedipine. Similarly, the shortening of single smooth muscle cells in response to KCl and mATP was potentiated by NPY (50 nM). The noradrenaline response was potentiated by NPY at 500 nM but not at 50 nM. Our results suggest that the potentiating effect of NPY is more specific to contraction mediated by nifedipine-sensitive calcium channels and is not dependent on the presence of an intact endothelium.


Oral nutrition interventions in patients undergoing gastrointestinal surgery for cancer: A systematic literature review.
Weight loss and poor food intake have been shown to affect several outcomes in patients undergoing surgery for gastrointestinal cancer. This review aims to examine the effect of pre-, post- or perioperative nutrition interventions focused on increasing oral energy or protein intake in patients undergoing surgery for gastrointestinal cancer. Interventions using standard oral nutrition supplements and/or dietary counselling were included. The primary outcome was weight change, and secondary outcomes were energy and protein intake. A secondary aim was to examine this effect in malnourished patients. Embase, Medline, CINAHL and CENTRAL were searched from inception to September 2019 for relevant randomised controlled trials. Study quality was assessed using the revised Cochrane Collaboration risk of bias tool for randomised trials. The quality of evidence for each outcome was assessed using GRADE. Fourteen articles met the inclusion criteria. Studies assessed patients undergoing surgery for gastric, colorectal, oesophageal and pancreatic cancers. The interventions studied included oral nutrition supplements and/or dietary counselling. Five studies reported preoperative interventions; five studies reported post-operative interventions; six studies reported post-discharge interventions; and two studies reported perioperative interventions. Overall, low or very low quality evidence was found to support the use of oral nutrition supplements to positively influence weight and increase energy and protein intake in the preoperative period and immediate post-operative period. Very low quality evidence was found to support the use of oral nutrition interventions to influence weight, energy or protein intake in the post-discharge period. Very limited evidence with high risk of bias was found to support positive effects of nutrition intervention in malnourished patients. This review demonstrates limited evidence for the use of oral nutrition supplements to increase intake and positively influence weight in patients undergoing surgery for gastrointestinal cancer. Overall, results were heterogeneous leading to inconsistent results. Further research into optimal nutrition support interventions and timing of interventions is required.


Models and objective functions for the optimisation of selectivity in reversed-phase liquid chromatography.
Interpretive methodologies are the most efficient tools for finding the optimal conditions in chromatography. These methodologies are supported by models or algorithms able to infer the system behaviour upon changes in the experimental factors. Once the models are built with data obtained from sets of carefully designed experiments, molecular modelling or other approaches, they can be applied to predict the performance of new conditions. The different elements involved in these methodologies, for both isocratic and gradient elution, are given. Special attention is devoted to the description of retention, owing to its major impact on the prediction of chromatographic resolution. Several models considering the main factors affecting retention (i.e. organic modifiers, pH and temperature), and procedures that enhance the predictions, are presented. Both the existence of skewed peaks and the effect of elution conditions on peak profiles are considered. Finally, the assessment of resolution, as well as other secondary aims that affect the practical suitability of the optimal conditions, is discussed.


Surgical, Oncological, and Functional Outcomes of Transoral Robotic Supraglottic Laryngectomy.
To investigate the surgical, oncological, and functional outcomes of transoral robotic surgery (TORS) for the treatment of supraglottic squamous cell carcinoma. Retrospective chart review. The charts of patients treated by TORS supraglottic laryngectomy (SGL) in an academic medical center were reviewed. The following outcomes were studied according to the tumor location: average robotic setup and operative times, mean estimated blood loss, postoperative complications, need of tracheotomy, refeeding characteristics, mean hospital stay, need of neck dissection and adjuvant therapy, 5-year local and regional controls, overall survival (OS), and disease-free survival (DFS). Seventy-five patients underwent TORS SGL. Tumors were classified as cT1 (32%), cT2 (52%), and cT3 (16%). Average robotic setup and operative times and the mean estimated blood loss were 15 minutes, 55 minutes, and 20 mL, respectively. The mean follow-up period ranged from 2 to 5 years. The 5-year OS and DFS were 80.2% and 94.3%, respectively. Overall, 34.6% of patients received adjuvant radiotherapy. The majority of patients (92%) restarted an oral diet within 24 to 48 hours postsurgery. Transient tracheotomy was performed in 8% of patients. Postoperative hemorrhages occurred in 12 patients (16.0%), lengthening the hospital stay (mean = 6.8 days). There were no outcome differences regarding the tumor location. TORS is an effective and safe therapeutic approach for early- and intermediate-stages cancers. Oncological outcomes may be quite similar to other surgical approaches, including transoral laser and open surgeries. Future randomized controlled studies are needed for comparing TORS SGL with other surgical procedures. 4 Laryngoscope, 131:1060-1065, 2021.


Genome-wide association analysis of cystatin-C kidney function in continental Africa.
Chronic kidney disease is becoming more prevalent in Africa, and its genetic determinants are poorly understood. Creatinine-based estimated glomerular filtration rate (eGFR) is commonly used to estimate kidney function, modelling the excretion of the endogenous biomarker (creatinine). However, eGFR based on creatinine has been shown to inadequately detect individuals with low kidney function in Sub-Saharan Africa, with eGFR based on cystatin-C (eGFRcys) exhibiting significantly superior performance. Therefore, we opted to conduct a GWAS for eGFRcys. Using the Uganda Genomic Resource, we performed a genome-wide association study (GWAS) of eGFRcys in 5877 Ugandans and evaluated replication in independent studies. Subsequently, putative causal variants were screened through Bayesian fine-mapping. Functional annotation of the GWAS loci was performed using Functional Mapping and Annotation (FUMA). Three independent lead single nucleotide polymorphisms (SNPs) (P-value <5 × 10-8 (based on likelihood ratio test (LRT))) were identified; rs59288815 (ANK3), rs4277141 (OR51B5) and rs911119 (CST3). From fine-mapping, rs59288815 and rs911119 each had a posterior probability of causality of >99%. The rs911119 SNP maps to the cystatin C gene and has been previously associated with eGFRcys among Europeans. With gene-set enrichment analyses of the olfactory receptor family 51 overlapping genes, we identified an association with the G-alpha-S signalling events. Our study found two previously unreported associated SNPs for eGFRcys in continental Africans (rs59288815 and rs4277141) and validated a previously well-established SNP (rs911119) for eGFRcys. The identified gene-set enrichment for the G-protein signalling pathways relates to the capacity of the kidney to readily adapt to an ever-changing environment. Additional GWASs are required to represent the diverse regions in Africa. Wellcome (220740/Z/20/Z).


Traumatic posterior dislocation of the hip--prognostic factors influencing the incidence of avascular necrosis of the femoral head.
To elucidate the factors important for development of avascular necrosis of the femoral head following traumatic posterior dislocation of the hip, 98 adult patients with 100 hip dislocations were reviewed after a minimum follow-up of 5 years. Avascular necrosis of the femoral head was found in only 4.8% of the hips reduced within 6 h, but in 52.9% of the hips reduced more than 6 h after the injury. Dislocations were classified according to Stewart and Milford [11]; a significantly higher incidence of avascular necrosis was found in grade-III and -IV dislocations than in grade-I and -II dislocations. We could not demonstrate any benefit from skeletal traction or non-weight bearing. The age of the patients was of no importance.


Fear of falling and changed functional ability following hip fracture among community-dwelling elderly people: an explanatory sequential mixed method study.
The aims of the study were to assess self-reported fear of falling (FOF) and functional ability among community-dwelling elderly people 3-6 months post hospital discharge after a hip fracture, to investigate the association between FOF and functional ability, and to explore the lived experience of FOF and disability when recovering from a hip fracture. A sequential explanatory mixed method design was used in a "face-to-face" survey assessing FOF (Falls Efficacy Scale-International, FES-I), avoidance of activities (Modified survey of Activities and Fear of Falling, mSAFFE), functional ability (Functional Recovery Score, FRS), and mobility (New Mobility Score, NMS) followed by in-depth interviews of four participants. Interviews were analyzed using systematic text condensation. Among the 33 participants 58% had a high degree of FOF and avoided more activities, needed more assistance in activities of daily living, and were less mobile than participants who had a low degree of FOF (p < 0.0001). According to the informants FOF reduced their functional ability and seriously altered their lives. FOF was common and significantly associated with activity avoidance, disability, and affected the lives of elderly recovering from a hip fracture. Some patients were physically incapacitated by FOF.


Catecholestrogens are MCF-7 cell estrogen receptor agonists.
Catecholestrogens are important metabolites of estradiol and estrone in the human. Considerable interest has focused on the catecholestrogens 2-hydroxy- and 4-hydroxyestradiol since they bind to the estrogen receptor with an affinity in the range of estradiol. Using the MCF-7 cell line, we analysed the capacity of purified catecholestrogens to transform the estrogen receptor into its high affinity nuclear binding form and to affect receptor-dependent processes such as proliferation and expression of the progesterone receptor (PR). Incubations with 2-hydroxy- and 4-hydroxyestradiol at 10(-8) M for 1 h resulted in tight nuclear binding of the estrogen receptor. During treatment of the cells with catecholestrogens we obtained a marked increase in proliferation rate of 36 and 76% for 2-hydroxy- and 4-hydroxyestradiol, respectively, relative to the inductive effect of estradiol (100%). The PR level, was slightly increased by treatment with 2-hydroxyestradiol (10%), whereas treatment with 4-hydroxyestradiol increased the PR level at 28%, compared to estradiol (100%). From these results we conclude that the 2- and 4-hydroxylated derivatives of estradiol are active hormones and are able to initiate estrogen receptor mediated processes in MCF-7 cells.


Delta sleep-inducing peptide (DSIP) stimulates growth hormone (GH) release in the rat by hypothalamic and pituitary actions.
To evaluate possible effects of delta sleep-inducing peptide on GH release, the peptide was micro-injected into conscious animals with third ventricular cannulae and blood samples were drawn from indwelling external jugular vein cannulae. Ovariectomized animals were used in order to eliminate gonadal steroid feedback. In the initial experiment, intraventricular injection of 5 micrograms of the peptide induced an elevation of GH which became significant by 30 min and persisted for the 120 min duration of the experiment after the injection. Diluent-injected animals showed a slight initial drop in GH and then no increase. The increase in plasma GH induced by the peptide was dose-related with a minimal effective dose of 0.1 microgram and a linear log-dose increase to a dose of 10 micrograms. This effect is presumably mediated hypothalamically via a dopaminergic mechanism since it could be blocked by pre-treatment of the animals with pimozide, a dopamine receptor blocker. Dispersed overnight, cultured pituitary cells from ovariectomized rats exhibited a dose-related increase in GH release in static incubations with DSIP. A response occurred with the lowest dose tested (10(-12) M) which increased to a maximum at 10(-10) M DSIP. The responses then declined at higher doses such that they were no longer significant at doses of 10(-7) and 10(-5) M. The increase even at the most effective dose was approximately 50% above the basal values. The results are consistent with the hypothesis that DSIP may be involved in GH release via a dopaminergic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)


[A search for association between the polymorphic markers of PON1 and PON2 genes and diabetic nephropathy in patients with type I diabetes mellitus].
Alleles and genotypes of polymorphic markers of paraoxonase 1 and paraoxonase 2 genes (PON1 and PON2) encoding enzymes of the body antioxidative defense were compared in type 1 diabetes mellitus patients with or without diabetic nephropathy. The patients with nonoverlapping ("polar") phenotypes constituted different groups. The first group contained patients with diabetic nephropathy (DN+, n = 62), clinical proteinuria (albuminuria above 300 mg per day), and at least 15-year disease duration. In control group, the patients had no diabetic nephropathy (DN-, n = 68), their albuminuria was below 200 mg per day, and disease duration was at least 20 years. Comparative analysis with exact Fisher's test revealed no significant differences in frequencies of alleles and genotypes of the PON1 gene polymorphic marker Gln192Arg and of PON2 gene polymorphic markers Ala148Gly and Cys311Ser. Our results suggest that the polymorphic markers studied are not associated with diabetic nephropathy among Russian patients in Moscow.


Hamiltonian dynamics of the SIS epidemic model with stochastic fluctuations.
Empirical records of epidemics reveal that fluctuations are important factors for the spread and prevalence of infectious diseases. The exact manner in which fluctuations affect spreading dynamics remains poorly known. Recent analytical and numerical studies have demonstrated that improved differential equations for mean and variance of infected individuals reproduce certain regimes of the SIS epidemic model. Here, we show they form a dynamical system that follows Hamilton's equations, which allow us to understand the role of fluctuations and their effects on epidemics. Our findings show the Hamiltonian is a constant of motion for large population sizes. For small populations, finite size effects break the temporal symmetry and induce a power-law decay of the Hamiltonian near the outbreak onset, with a parameter-free exponent. Away from the onset, the Hamiltonian decays exponentially according to a constant relaxation time, which we propose as a metric when fluctuations cannot be neglected.


Use of Thermoplastic Rings Following Venting of Flexor Tendon Pulleys: A Biomechanical Analysis.
Normal digital flexion relies on flexor tendon pulleys to convert linear muscular force to angular digital motion. However, there is a growing trend to vent them partially during flexor tendon repair. The objective of this study was to examine the effects of a thermoplastic ring, acting as an external pulley, on flexor tendon biomechanics and finger range of motion (ROM) after pulley venting. We tested 15 cadaveric digits using an in vitro active finger motion simulator. We measured loads induced by flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) as well as joint ROM with sequential sectioning of the A2, A3, and A4 pulleys compared with an intact pulley condition. At each stage, external thermoplastic pulley rings were applied snugly over the proximal and middle phalanges to recreate A2 and A4 function, respectively. After complete venting of the A2, A3, and A4 pulleys, proximal interphalangeal joint ROM significantly decreased by 13.4° ± 2.7° and distal interphalangeal joint ROM decreased by 15.8° ± 2.1°. Application of external rings over the proximal and middle phalanx resulted in a residual ROM decrease of 8.3° ± 1.9° at the proximal interphalangeal joint and 7.9° ± 2.1° at the distal interphalangeal joint, nearly restoring ROM. Similarly, complete pulley venting resulted in reduced FDS load by 37% and FDP load by 50% compared with intact pulleys. After application of external rings, loads were restored almost to normal, with a 9% reduction for FDS load and 9% reduction for FDP load compared with intact pulleys. The application of thermoplastic rings acting as external pulleys is an effective, noninvasive, and reproducible approach to restore flexor tendon biomechanics and digit ROM after pulley venting. Thermoplastic rings may be a useful therapeutic adjunct in restoring joint ROM and flexor tendon loads after surgical venting of the pulleys.


The Blood-Brain Barrier in Neuroimmune Interactions and Pathological Processes.
The blood-brain barrier (BBB) is a kind of filter, highly selective in relation to various types of substances. The BBB supports the immune status of the brain and is an important regulator of neuroimmune interactions. Some of the molecular and cellular features of the BBB, as well as the five main pathways of neuroimmune communication mediated by the BBB, are analyzed in this article. The functions of the BBB in neuroimmune interactions in various diseases are discussed: multiple sclerosis and Alzheimer's and Parkinson's diseases. The latest data on BBB dysfunction in COVID-19 coronavirus infection caused by the SARS-CoV-2 virus are considered.


Accurate assessment of estrogen receptor profiles in non-functioning pituitary adenomas using RT-digital PCR and immunohistochemistry.
Non-functioning pituitary adenomas (NFPAs) are common pituitary tumors, and surgery is generally the only treatment option. Few attempts have been made to explore target molecules for the development of NFPA pharmacological treatments. We quantitatively assessed the expression profiles of estrogen receptor (ER) transcripts and proteins in NFPA samples, using reverse transcription-digital polymerase chain reaction (RT-dPCR) and immunohistochemistry, and further investigated the correlations between the expression levels of ER and those of downstream responsive genes. All patients had undergone surgery at the same high-volume hospital. A total of 20 patients with NFPAs were included. All patients were new-onset, and none were diagnosed with intratumoral hemorrhages or cysts. NFPA samples exhibited a bimodal ESR1 expression pattern and were categorized into significantly different high- and low-ESR1 expression level groups (P < 0.05). In contrast, expression levels of ESR1 variants and ESR2 could barely be detected. Similar results were obtained through the immunohistochemical staining of NFPAs, using well-validated antibodies against ERs. The expression levels of ESR1 positively correlated with those of GREB1, an estrogen-responsive gene [correlation coefficient (r) = 0.623, P = 0.003]. ESR1 expression levels in NFPAs exhibited a bimodal pattern and were positively correlated with GREB1 expression levels. The accurate assessment of ER expression levels may further advance future NFPA-related research.


Design, synthesis and antiproliferative properties of oligomers with chromophore units linked by amide backbones.
The preparation of oligomers made up of several chromophore units as compounds with potential fluorescent and antiproliferative properties is described. Specifically, chromophore units with protected-amino groups and one carboxylic group are described, together with methods to assemble these units using peptide chemistry. Some of these compounds have antiproliferative activity.


Comparison of the analytical performance of the Oncomine dx target test focusing on bronchoscopic biopsy forceps size in non-small cell lung cancer.
Next-generation sequencing (NGS) has been implemented in clinical oncology to analyze multiple genes and to guide targeted therapy. Although the pathological diagnosis and biomarker tests for patients with advanced lung cancer have mostly been obtained with small biopsy samples, especially with bronchoscopic approaches, the performance for NGS with respect to the different sizes of biopsy forceps remains little known. We retrospectively reviewed consecutive patients with non-small cell lung cancer, whose FFPE samples were obtained by endobronchial biopsy/transbronchial biopsy and were submitted for the Oncomine Dx Target Test (ODxTT). We compared the analytical performance for ODxTT with respect to the size of biopsy forceps. A total of 103 samples were identified. The success rate of the ODxTT for the group with all samples obtained with small forceps biopsies (70%) was lower than that of the group with some or all samples obtained with standard forceps biopsies (83%), although without a statistically significant difference (p = 0.20). With regard to the reason for unsuccessful analysis, the proportion of the samples which did not pass the nucleic acid concentration threshold in the former group (15%) was higher compared with that of the latter group (4%) (p = 0.08). The proportion of tissue size 4 mm2 or larger in the former group (70%) was lower than that in the latter group (93%) (p = 0.01). The analysis of ODxTT for specimens biopsied using only small forceps is prone to be unsuccessful due to an insufficient amount of nucleic acid.


Phase angle as a severity indicator for liver diseases.
The aim of this study was to evaluate the applicability of phase angle (PhA) as a severity indicator of chronic liver diseases. We examined the medical records of 54 patients-27 with hepatocellular carcinoma (HCC) and 27 with non-alcoholic fatty liver disease (NAFLD). The patients were ≥18 y of age. Clinical data, such as Child-Pugh and Barcelona Clinic Liver Cancer (HCC), aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis (FIB)-4 (NAFLD), nutritional parameters (body mass index [BMI], handgrip strength [HGS], and bioelectrical impedance [BIA] data) were collected. Nutritional Risk Index (NRI) was calculated. Analysis was performed using Mann-Whitney test and analysis of variance. Simple multiple linear regression for predictions (Child-Pugh in HCC, APRI and FIB-4 in NAFLD). Receiver operating characteristic curve was estimated to search a cutoff for PhA. For survival, we used the Kaplan-Meier estimator. To verify whether PhA affected patients' survival, we used the Mantel-Haenszel. The prevalence of cirrhosis was high in HCC (n = 25) and low in the NAFLD (n = 4). No patient was classified as undernourished based on BMI; however, NRI showed that 74.1% of patients with HCC had nutritional risk. Child-Pugh was positively correlated with the edema index (extracellular water/total body water [ECW/TBW]) and negatively correlated with PhA and HGS. Higher Child-Pugh and BCLC scores were associated with worse NRI. APRI and FIB-4 were positively correlated with weight and BMI. A significant difference between groups was found for the median values of R, ECW/TBW, PhA, HGS, and albumin. There was a trend toward lower survival in patients with HCC, according to the cutoff point of 5.1 degrees for PhA. PhA was shown to be an independent prognostic indicator for cirrhosis and may be related to survival in these patients.


Indocyanine green-assisted internal limiting membrane peeling for macular holes: toxicity?
Indocyanine green (ICG) staining facilitates definitive internal limiting membrane (ILM) peeling during macular hole surgery (MHS), but might cause toxicity. To determine if ICG to assist in ILM peeling has an effect on anatomic or visual results in MHS with ILM peeling. Retrospective, comparative review including primary analysis of 173 cases undergoing MHS. Visual acuity >or=20/50, <or=20/200, three-line visual acuity improvement, and anatomic success rates were analyzed as endpoints. The single operation hole closure rate was 87% with ICG versus 83% without ICG (P = 0.52). Postoperative median best-corrected visual acuity was 20/70 and 20/80 in the ICG and no ICG groups with median follow-up intervals of 8 and 9 months. The use of ICG was associated with a higher rate of <or=20/200, but ILM peeling and ICG use was not associated with better anatomic success, visual improvement, or >or=20/50 visual acuity. ICG usage during macular hole surgery was not associated with worse visual outcomes, suggesting possible toxic effects reported are not clinically significant. If the ILM cannot be peeled effectively, ICG should be considered a safe option.


Towards unraveling the origins of eukaryotic nuclear genome organization.
With 3D genome mapping maturing over the past decade, studies exposed the differences between eukaryotic and prokaryotic genome organization. This raises the question of how the complex eukaryotic genome organization originated. Here, I explore potential pathways to answering this question, guided by our changing understanding of the origins of eukaryotes.


The role of visfatin and resistin in an in vitro model of obesity-induced invasive liver cancer.
Obesity is associated with the development of liver disease and its progression to hepatocellular carcinoma. This link may be attributed to adipocytokines such as visfatin and resistin which have been shown to promote liver cancer incidence and progression. Studies have yet to determine the role of visfatin and resistin in liver cancer, specifically in the context of obesity. The objective of this study was to investigate the effect of neutralizing visfatin and resistin in obese (OB) or normal weight (NW) sera to determine the contribution of these proteins in obesity-induced invasive liver cancer. Sera from OB or NW males was used to determine the efficacy of neutralizing visfatin and resistin to reduce the obesity-induced liver cancer phenotype. HepG2 and SNU-449 cells were exposed to OB and NW sera ± antibodies for visfatin or resistin. The neutralizing antibodies differentially suppressed invasion, reactive oxygen species production, and matrix metalloproteinase-9 secretion. These changes corresponded with a decrease in phosphorylated extracellular signal-regulated kinases and protein kinase B in HepG2 cells, but differences were not observed in CAP1 or β-catenin. In conclusion, visfatin and resistin have differential roles in obesity-associated liver cancer and may be potential targets to reverse the impact of obesity on liver cancer progression.


[The development of degenerative disc animal model in rhesus monkey].
To develop the degenerative disc animal model with histological and MRI observation. Eight adult Rhesus monkeys were divided randomly into two groups after the lumbar discs MRI scan. The operated group, 6 monkeys, was subjected to annulus resection. A 5 mm x 3 mm cut was made in the left anterolateral part of the fibrosus annulus on L(4,5), L(5,6) and L(6,7) discs. The operated discs were scanned with MRI at 1 week, 4 weeks, 8 weeks, 13 weeks and 20 weeks postoperatively and observed histologically at 4 weeks, 8 weeks and 20 weeks after operation. The histological structure of Rhesus monkey was similar to that of human being. The percentage of high signal intensity area in the operated discs reduced significantly at 8, 13, 20 weeks after operation (P < 0.05). The fibroplasia outside the annular tear could be observed in all 6 operated discs at 4 weeks postoperatively. Two of 6 operated discs underwent fibroplasia at 20 weeks after operation. No heal evidence in the inner tear was showed after operation. The animal model for human lumbar disc degeneration could be obtained by anterio-lateral annulus resection. The early-stage degenerative evidence could be observed without injury by measuring the percentage of the high intensity area of the operated discs on T2WI of MRI.


Radioactive Seed Versus Wire-Guided Localization for Ductal Carcinoma in Situ of the Breast: Comparable Resection Margins.
There are currently two widely used methods for preoperative localization of ductal carcinoma in situ (DCIS) of the breast: wire-guided localization (WGL) and radioactive seed localization (RSL). Several studies compared these localization techniques in small cohorts. The aim of this study was to compare the surgical resection margin status between RSL and WGL in a large national cohort of patients with DCIS. We included patients from the Dutch Pathology Registry who underwent breast-conserving surgery for DCIS by either RSL (n = 1851) or WGL (n = 2187) between 2009 and 2019. Several clinicopathological characteristics were compared between these two groups, including resection margin status and number of re-excisions. Patients undergoing RSL were younger (p = 0.014) and were more often diagnosed with a large DCIS (p = 0.013), high grade DCIS (p < 0.001) and comedonecrosis (p < 0.001) compared with patients undergoing WGL. There was no significant difference in resection margin status between both groups (p = 0.089) and the number of re-excisions (p = 0.429). However, in case of re-excision, patients in the RSL group were more often treated with breast-conserving surgery (p = 0.029). In this large national cohort study of patients with DCIS, we demonstrated that there was no difference in resection margin status between both procedures, or in the number of re-excisions, but patients in the RSL group were more often treated with breast-conserving therapy in case of a re-excision.


Ether lipid generating enzyme AGPS alters the balance of structural and signaling lipids to fuel cancer pathogenicity.
Aberrant lipid metabolism is an established hallmark of cancer cells. In particular, ether lipid levels have been shown to be elevated in tumors, but their specific function in cancer remains elusive. We show here that the metabolic enzyme alkylglyceronephosphate synthase (AGPS), a critical step in the synthesis of ether lipids, is up-regulated across multiple types of aggressive human cancer cells and primary tumors. We demonstrate that ablation of AGPS in cancer cells results in reduced cell survival, cancer aggressiveness, and tumor growth through altering the balance of ether lipid, fatty acid, eicosanoid, and fatty acid-derived glycerophospholipid metabolism, resulting in an overall reduction in the levels of several oncogenic signaling lipids. Taken together, our results reveal that AGPS, in addition to maintaining ether lipids, also controls cellular utilization of fatty acids, favoring the generation of signaling lipids necessary for promoting the aggressive features of cancer.


Health-related Quality of Life in Intermediate- or High-risk Patients Treated With Radical External Radiotherapy and Adjuvant Docetaxel for Localized Prostate Cancer: A Randomized, Phase III SPCG-13 Study.
The goal of this study was to investigate whether health-related quality of life (HRQoL) was affected in patients with high- or intermediate-risk localized prostate cancer treated with docetaxel following radiation therapy (RT). A total of 376 patients treated with RT and androgen deprivation were randomized to receive 6 cycles of docetaxel 75 mg/m2 (N=188, Arm A) or surveillance (N=188, Arm B). FACT-P HRQoL questionnaires were gathered at baseline, six months and 1, 2 and 4 years after randomization. The data were analysed using analysis of covariance. FACT-P scores decreased in Arm A at the end of treatment and remained unchanged in Arm B (p<0.0001). The HRQoL scores in Arm A matched Arm B in the 1-year follow-up (p=0.0528) and remained similar in further follow-up. Docetaxel transiently decreased HRQoL during chemotherapy but not after treatment for up to four years of follow-up.


A Case Report of Venezuelan Suntiger Tarantula (Psalmopoeus Irminia) Envenomation and Review of Tarantula Exposures.
Tarantula envenomations are encountered infrequently but may increase with increased exotic animal ownership. This case report presents the first documented toxicity from a Venezuelan suntiger tarantula (VST), Psalmopoeus irminia, and provides a general framework for approaching patients with tarantula exposures. A 35-year-old man presented to an emergency department 4 h after experiencing a bite from his pet VST. He developed erythema, pain, and edema to the bite site on the left thenar eminence that extended proximally. Within 4 h, he developed abdominal pain, nausea, vomiting, throat itching, and tightness. The patient had a blood pressure of 131/105 mm Hg, heart rate of 102 beats/min, 36.6°C, respiratory rate of 20 breaths/min, and SpO2 of 94%. Laboratory evaluations were within normal limits (other than chronically elevated but improved transaminases). The patient received 0.5 mg epinephrine intramuscularly, 50 mg diphenhydramine IV, 20 mg famotidine IV, 0.4 mg ondansetron IV, and 1 L of normal saline for a suspected anaphylactic reaction. Shortly after epinephrine administration, his gastrointestinal and upper airway symptoms resolved. All symptoms resolved within 1 week. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Little is known about VST toxicity. Therefore, providers should rely on a general framework for approaching patients with tarantula exposures. Morbidity from tarantula exposures is mediated by mechanical injury, venom effects, and hypersensitivity reactions. Typical clinical findings include local pain, pruritis, edema, erythema, and burning. Muscle cramping, ophthalmia nodosa, and hypersensitivity reactions may occur. Treatment is primarily supportive and includes decontamination, cool compresses, analgesia, treatment of anaphylaxis, and ophthalmology evaluation if ocular exposure.


[Study of fluoride released from fluoride-releasing adhesives].
To study the fluoride release ability of two kinds of fluoride-releasing composite resin adhesives made in China. Test samples of fluoride-releasing composite resin adhesives I and II were prepared, and fluoride ion concentrations were measured with a No.720 fluoride ion-sensitive electrode. Fluoride ions were released from both of the fluoride-releasing composite resin adhesives. The concentration declined sharply after first 24 hours and maintained at a low level for about 21 days. The initial fluoride ions concentration of adhesive II was higher than adhesive I. Both of the fluoride-releasing composite resin adhesives had the ability of releasing fluoride. Adhesive II seemed better.


The influence of cyproteron-acetate orally on the hair root status in women with idiopathic hirsutism.
The hair root status was used to evaluate the effect of cyproterone-acetate (CA), given orally, on hair cycle in a clinically homogeneous group of 11 women with idiopathic hirsutism. The therapy was continued for 12 menstrual cycles of treatment. The hair root status on the left upper leg and chin was determined before, directly after CA-treatment and 3 months later. The absolute number of anagan hair roots in both fields was decreased directly after therapy. Three months later this value on the upper leg increased again significantly while on the chin there was no significant increase in this period. The number of catagen/telogen hair roots showed no significant differences before, directly after CA-treatment and 3 months later. The number of regrowing hairs on the upper leg showed a significant increase of dysplastic-dystrophic hair roots.


Microwave assisted extraction followed by gas chromatography with tandem mass spectrometry for the determination of triclosan and two related chlorophenols in sludge and sediments.
A procedure for the determination of 2-(2,4-dichlorophenoxy)-5-chlorophenol (Triclosan) and two possible transformation compounds, 2,4-dichlorophenol (2,4-DCP) and 2,4,6-trichlorophenol (2,4,6-TCP), in sludge from sewage treatment plants (STP) and sediments is presented. Extraction was performed using an acetone:methanol (1:1) mixture under the action of a microwave field. The centrifuged supernatant was diluted with a NaOH aqueous solution and twice extracted with n-hexane for removing neutral and basic interferences. The aqueous layer was acidified and processed as a waste water sample. After concentration analytes were silylated and determined by gas chromatography with tandem mass spectrometry (GC-MS/MS). Influence of experimental conditions on the yield of the extraction process and on the efficiency of the further clean-up step was thoroughly evaluated. Performance of MS/MS detection in comparison to single MS is described. Under final working conditions quantification limits between 0.4 and 0.8 ng/g and recoveries from 78% to 106% were obtained. The method was applied to the analysis of several sludge and sediment samples. Only low levels of TCS were detected in some of the sediments; however, all three compounds were found in sludge samples at concentrations ranging from 7 to 316 ng/g, in the case of chlorophenols, and from 420 to 5400 ng/g, for Triclosan.


Evaluating Potential Autologous Bypass Grafts with Tomographic Three-Dimensional Ultrasound Compared with Standard Color Duplex.
Vein mapping using duplex ultrasound (DUS) is a routine in selecting optimal autologous bypass grafts (aBG) but is time consuming and operator-dependent. Tomographic three-dimensional (3D) ultrasound (tUS), using free-hand electromagnetic tracking, allows cardiac and vascular surgeons to view 3D images of the entire length of the potential bypass graft. This study compares tUS with DUS in the evaluation of potential autologous grafts for coronary and lower limb bypass. Both DUS and tUS imaging of 434 potential autologous grafts (364 long, 22 short saphenous veins, and 48 radial artery) immediately before bypass surgery were compared. The time in minutes to evaluate each aBG was recorded. Surgeons scored the quality of the aBG at operation. A score of 5 was in complete agreement with preoperative imaging with scores of 4 considered "good". Most operating surgeons (113, 57%) preferred interpreting the tUS images and felt that this technology could replace DUS completely. The choice of aBG would have been changed as a result of tUS images in 64 (32%) cases. DUS imaging took a mean (+/-sd) of 08:26 ± 04:44 minutes compared with only 01:00 ± 00:25 minutes for tUS (P < 0.001). However, processing the tUS images, which is currently done manually by the vascular scientist, took significantly longer at 19:31 ± 12:41 minutes compared with 09:03 ± 09:12 minutes for reporting DUS (P < 0.001). Surgeons preferred to see tUS images of the potential aBG themselves rather than relying on DUS reports. tUS images were significantly quicker than DUS to acquire but needed more processing time.


Sf3b4 regulates chromatin remodeler splicing and Hox expression.
SF3B proteins form a heptameric complex in the U2 small nuclear ribonucleoprotein, essential for pre-mRNA splicing. Heterozygous pathogenic variants in human SF3B4 are associated with head, face, limb, and vertebrae defects. Using the CRISPR/Cas9 system, we generated mice with constitutive heterozygous deletion of Sf3b4 and showed that mutant embryos have abnormal vertebral development. Vertebrae abnormalities were accompanied by changes in levels and expression pattern of Hox genes in the somites. RNA sequencing analysis of whole embryos and somites of Sf3b4 mutant and control litter mates revealed increased expression of other Sf3b4 genes. However, the mutants exhibited few differentially expressed genes and a large number of transcripts with differential splicing events (DSE), predominantly increased exon skipping and intron retention. Transcripts with increased DSE included several genes involved in chromatin remodeling that are known to regulate Hox expression. Our study confirms that Sf3b4 is required for normal vertebrae development and shows, for the first time, that like Sf3b1, Sf3b4 also regulates Hox expression. We propose that abnormal splicing of chromatin remodelers is primarily responsible for vertebral defects found in Sf3b4 heterozygous mutant embryos.


Study of chromosome rearrangements associated with the trpE26 mutation of Bacillus subtilis.
Chromosome rearrangements involved in the formation of merodiploid strains in the Bacillus subtilis 168-166 system were explained by postulating the existence of intrachromosomal homology regions. This working hypothesis was tested by analysing sequences and restriction patterns of the, as yet uncharacterized, junctions between chromosome segments undergoing rearrangements in parent, 168 trpC2 and 166 trpE26, as well as in derived merodiploid strains. Identification, at the Ia/Ib chromosome junction of both parent strains, of a 1.3 kb segment nearly identical to a segment of prophage SPbeta established the existence of one of the postulated homology sequences. Inspection of relevant junctions revealed that a set of different homology regions, derived from prophage SPbeta, plays a key role in the formation of so-called trpE30, trpE30+, as well as of new class I merodiploids. Analysis of junctions involved in the transfer of the trpE26 mutation, i.e. simultaneous translocation of chromosome segment C and rotation of the terminal relative to the origin moiety of the chromosome, did not confirm the presence of any sequence suitable for homologous recombination. We propose a model involving simultaneous introduction of four donor DNA molecules, each comprising a different relevant junction, and their pairing with the junction regions of the recipient chromosome. The resolution of this structure, resting on homologous recombination, would confer the donor chromosome structure to the recipient, achieving some kind of 'transstamping'. In addition, a rather regular pattern of inverse and direct short sequence repeats in regions flanking the breaking points could be correlated with the initial, X-ray-induced, rearrangement.


Biological and biochemical characterization of a new isolate of feline sarcoma virus: Theilen-Pedersen (TP1-FeSV).
A new feline sarcoma virus designated Theilen-Pedersen (TP1-FeSV) has been isolated from a spontaneous, slowly growing fibrosarcoma of a domestic short-haired 4-year-old castrated cat. The virus codes for a gag-onc fusion protein of 83,000 molecular weight phosphorylated in vivo at serine, threonine, and tyrosine residues. Cells transformed in vitro with TP1-FeSV exhibit five- to 10-fold elevated levels of phosphotyrosine over FeLV-infected cells. The gag-onc polyprotein has associated with it a tyrosyl protein kinase activity which in vitro results in autophosphorylation of the molecule at tyrosine residues. The fusion protein cannot be labeled metabolically with [3H]glucosamine and tunicamycin has no effect on the electrophoretic mobility of the in vivo [32P]orthophosphate-labeled fusion protein. The fusion protein, in common with the gag precursor Pr65gag, can be metabolically labeled with palmitic acid.


Overexpression of isoform B of Dgp-1 gene enhances locomotor activity in senescent Drosophila males and under heat stress.
Here, we describe the longevity and locomotor behavior of senescent Drosophila males with altered expression of Dgp-1 gene. In comparison with the wild-type Canton-S (CS) males, six characteristics of the phenotype of Dgp-1[843k] mutant were found: (1) low expression of isoform A; (2) augmented expression of isoform B; (3) reduction in the mean lifespan; (4) decrease in the running speed in 3-day-old flies; (5) maintenance of a high run frequency in senescent flies; and (6) resistance to heat stress manifested as maintenance of a high run frequency at 29 °C. After cessation of "cantonization" process, mean lifespan of the mutant males drifted from low to high values finally exceeding that for CS. In contrast, behavioral phenotype of the mutant was robust. Using the GAL4/UAS system, we showed that neurospecific overexpression of isoform B resulted in a slight decrease of longevity and a high level of run frequency in the senescent flies, similar to that in Dgp-1[843K] mutant. In addition, a decreased level of reactive oxygen species was found in Dgp-1[843K] mutant males maintained under stress conditions. The elevated resistance to oxidative stress probably explains the two distinctive features of the mutation: resistance to aging processes and thermal stress displayed at behavioral level.


Influence of tissue fixation on the microextraction and identification of amyloid proteins.
In surgical pathology, correct immunohistochemical identification of AL amyloidosis poses a particular problem. Immunostaining for lambda- or kappa-light chains is commonly encountered even in non-immunoglobulin-derived amyloidoses, which leads to a false-positive classification as AL amyloidosis. In this respect, microextraction of amyloid proteins from surgical pathology specimens and their subsequent biochemical characterization may prove useful in reaching the correct diagnosis. In this study, we investigated systematically the influence of fixation on the extraction of amyloid proteins from amyloid-containing tissue samples. Tissue samples were obtained from a patient with generalized AA amyloidosis and from a second patient with generalized AL amyloidosis. The samples were stored either unfixed or fixed in phosphate buffered 4% p-formaldehyde, methacarn, or Bouin for 3 days, 1 week, or 1 month. Thereafter, proteins were extracted according to the procedure of Layfield et al, separated by SDS-PAGE and subjected to Western blotting, using antibodies directed against AA amyloid and immunoglobulin-derived lambda-light chain. Following this procedure, a variety of differently sized AA amyloid or lambda-light chain immunoreactive protein bands were found in both patients, which is typical for amyloid proteins. Fixation time did not per se prohibit the extraction of these amyloid proteins from tissue samples, which remained detectable irrespective of fixation time. Although all three fixatives impaired the resolution of some, but not all, individual amyloid proteins, this procedure may help to confirm or reject a diagnosis of AL amyloidosis, because detection of several lambda- or kappa-light chain immunoreactive protein bands in the low-molecular-weight range (<20 kDa) is a common characteristic of their amyloid nature.


The Use of Data Collection and Big Data Analysis in Neurodegenerative Disease Prevention.
Data collection and analysis is becoming more and more important in our everyday lives. It is widely believed that with the power of data collection, almost every problem can be given a possible solution. Machine learning and artificial intelligence algorithms along with the use of the Alzheimer's Disease Neuroimaging Initiative (ADNI) database that collects data from subjects suffering from Alzheimer's disease (AD) can be utilised for recognising biomarkers' patterns that suggest degenerative behavior. Thus, allowing for early prevention. Computers are able to distinguish patterns over millions of data faster than humans can. The suggested methodology will be able to precisely find subjects that might suffer from such diseases due to certain patterns and biomarkers that suggest such predisposition at an early and thus treatable stage of the disease. Due to the quantity of the data collected, an algorithm will be able to distinguish even the slightest change in a healthy neuron in order to treat it. Other databases can be used for other diseases without the concept being changed.


The HSV-1 tegument protein pUL46 associates with cellular membranes and viral capsids.
The molecular mechanisms responsible for the addition of tegument proteins into nascent herpesvirus particles are poorly understood. To better understand the tegumentation process of herpes simplex virus type 1 (HSV-1) virions, we initiated studies that showed the tegument protein pUL46 (VP11/12) has a similar cellular localization to the membrane-associated tegument protein VP22. Using membrane flotation analysis we found that pUL46 associates with membranes in both the presence and absence of other HSV-1 proteins. However, when purified virions were stripped of their envelope, the majority of pUL46 was found to associate with the capsid fraction. This strong affinity of pUL46 for capsids was confirmed by an in vitro capsid pull-down assay in which purified pUL46-GST was able to interact specifically with capsids purified from the nuclear fraction of HSV-1 infected cells. These results suggest that pUL46 displays a dynamic interaction between cellular membranes and capsids.


[Delirium during oral therapy of herpes zoster with acyclovir. Case report and brief review of central nervous system side-effects of acyclovir].
In differential diagnosis of a delir also adverse effects of medicaments have to be taken into account beside other causes. We report a case of an agitated delir with nocturnal disturbance of consciousness, confusion, restlessness and sleeplessness. This delir existed exclusively during the therapy of a cutaneous herpes zoster with zovirax-pills which can only be explained by a causal connection--after exclusion of other causes. As a so far undescribed predisposition for neurotoxicity of oral therapy with acyclovir signs of vascular encephalopathy were found in the patient's cranial magnetic resonance imaging. The central nervous side effects of acyclovir were summarized shortly.


The influence of the gene sb in Culex pipiens on the development of sub-periodic Brugia malayi and Wuchereria bancrofti.
The gene sb (filarial susceptibility, Brugia pahangi) in Culex pipiens controls the development also of sub-periodic B. malayi, but has no influence on the development of periodic Wuchereria bancrofti (Ceylon strain). C.p. fatigans (Kuala Lumpur), C.p. molestus (London) and Aedes aegypti (re fm strain) were all susceptible to the Ceylon strain of W. bancrofti, with susceptibility rate of 90.3%, 92.9% and 52.6% respectively. However, a low proportion of the larvae in A. aegypti developed to maturity, and this mosquito is less well adapted to W. bancrofti than is C. pipiens.


Segmental arterial mediolysis with 5 splenic artery aneurysms. A rare finding of a rare disease: Case report and literature review.
Splenic artery aneurysms (SAA) are uncommon findings. They are usually single and isolated; however they can be multiple; hence vasculopathy and segmental artery mediolysis may be considered. In our manuscript we present a case of a 54year old multiparous lady who was discovered incidentally to have a diseased splenic artery containing five SSAs. The largest aneurysm was close to the takeoff of the vessel and the smallest was distal embedded in the splenic hilum. Endovascular option was technically not feasible. Therefore the patient underwent a complete splenic artery resection with splenectomy and the histopathologic examination was suggestive of segmental arterial mediolysis (SAM). Multiple SAAs remains a rare finding of a rare disease. Complications can be crucial and high index of suspicion is important. Segmental arterial mediolysis can be considered in patients with several aneurysms on one anatomic site; Angiography is the gold standard diagnostic and therapeutic method. Complete splenic artery resection with splenectomy is the best treatment option for solitary vessel involvement.


Evaluation of nasal mucociliary clearance by saccharine test in rheumatoid arthritis.
We aimed to reveal whether there is nasal involvement by examining the Nasal Mucociliary Clearance (NMC) and the relationship between this activity and disease severity in Rheumatoid Arthritis (RA) patients. In this prospective study, NMC time, disease activity (Disease Activity Score 28) and blood parameters of RA patients (n = 87) were investigated and compared with the healthy control group (n = 50). In addition, the relationship between DAS 28 and NMC was investigated. The mean NMC of the RA group was 9.51 ± 3.54 min, the mean NMC of the control group was 8.69 ± 2.85 min, and there was no significant difference between the two groups. There was no correlation between NMC and disease duration, and DAS 28. The mean NMC of the RA patients with Anti Cyclic Citrulled Peptide (Anti-CCP) positive was significantly higher than the negative ones. Although there was no significant difference in NMC values between the RA and control group, the NMC of the Anti-CCP positive patients was higher. Level 2.


Optical polarization from colliding stellar stream shocks in a tidal disruption event.
A tidal disruption event (TDE) occurs when a supermassive black hole rips apart a passing star. Part of the stellar material falls toward the black hole, forming an accretion disk that in some cases launches a relativistic jet. We performed optical polarimetry observations of a TDE, AT 2020mot. We find a peak linear polarization degree of 25 ± 4%, consistent with highly polarized synchrotron radiation, as is typically observed from relativistic jets. However, our radio observations, taken up to 8 months after the optical peak, do not detect the corresponding radio emission expected from a relativistic jet. We suggest that the linearly polarized optical emission instead arises from shocks that occur during accretion disk formation, as the stream of stellar material collides with itself.


Development of MCTS technique for 3-PM liquid scintillation counting.
We have developed a multi-channel time scaling method that is suitable for activity measurement of beta emitting nuclides by means of 3-PM Liquid Scintillation Counting, using non-extending dead times and linear amplifiers. Since it enables to obtain the accidental coincidences directly, the true values for both double and triple coincidences are determined by simply taking into account the correction due to dead times. The advantages of the method are demonstrated by studying the activity of 204Tl and 14C. The measured results were compared with those derived by using the mathematical formulae.


Implications of WHO COVID-19 interim guideline 2020.5 on the comprehensive care for infected persons in Africa Before, during and after clinical management of cases.
The novel coronavirus disease 2019 (COVID-19) is one of the biggest public health crises globally. Although Africa did not display the worst-case scenario compared to other continents, fears were still at its peak since Africa was already suffering from a heavy load of other life-threatening infectious diseases such as HIV/AIDS and malaria. Other factors that were anticipated to complicate Africa's outcomes include the lack of resources for diagnosis and contact tracing along with the low capacity of specialized management facilities per capita. The current review aims at assessing and generating discussions on the realities, and pros and cons of the WHO COVID-19 interim guidance 2020.5 considering the known peculiarities of the African continent. A comprehensive evaluation was done for COVID-19-related data published across PubMed and Google Scholar (date of the last search: August 17, 2020) with emphasis on clinical management and psychosocial aspects. Predefined filters were then applied in data screening as detailed in the methods. Specifically, we interrogated the WHO 2020.5 guideline viz-a-viz health priority and health financing in Africa, COVID-19 case contact tracing and risk assessment, clinical management of COVID-19 cases as well as strategies for tackling stigmatization and psychosocial challenges encountered by COVID-19 survivors. The outcomes of this work provide links between these vital sub-themes which may impact the containment and management of COVID-19 cases in Africa in the long-term. The chief recommendation of the current study is the necessity of prudent filtration of the global findings along with regional modelling of the global care guidelines for acting properly in response to this health threat on the regional level without exposing our populations to further unnecessary adversities.


Chiral All-Nitrogen-Coordinated Dysprosium Single-Molecule Magnets.
Two pairs of chiral end-on azido-bridged dinuclear hexaazamacrocycles, [Dy2 (LN6 R/S )2 (N3 )2 Cl2 ](BPh4 )2 (1R/1S) and [Dy2 (LN6 R/S )2 (N3 )4 ]Cl2 (2R/2S) (LN6 R/S is hexaazamacrocyclic neutral Schiff base ligand derived from 2,6-diformylpyridine and (1R, 2R)/(1S, 2S)-diaminocyclohexane), were constructed by adjusting the molar ratio of sodium azide to Dy(III) macrocycle precursor. Structural analyses reveal that all Dy(III) centers in complexes 1R/1S and 2R/2S are nine-coordinate with hula-loop coordination geometry, and the differences between 1R/1S and 2R/2S are the terminal coordination anion and counter anion. Magnetic studies indicate that complex 2S displays typical SMM behaviors under a zero dc field, whereas 1S just shows slow relaxation of magnetization resulting from a relatively weak axial crystal field. Significantly, complex 2R/2S represents the first homochiral all-nitrogen-coordinated lanthanide single-molecule magnet.


Respective roles of the glutamine synthetase/glutamate synthase cycle and glutamate dehydrogenase in ammonium and amino acid metabolism during germination and post-germinative growth in the model legume Medicago truncatula.
Our objective was to determine the respective roles of the couple glutamine synthetase/glutamate synthase (GS/GOGAT) and glutamate dehydrogenase (GDH) in ammonium and amino acid metabolism during germination and post-germinative growth in the model legume Medicago truncatula Gaertn. For this aim, amino acids were analyzed by HPLC and changes in gene expression of several enzymes involved in N and C metabolism were studied by real-time quantitative reverse transcription-polymerase chain reaction. Among the enzymes studied, GDH showed the highest increase in gene expression (80-fold), specifically in the embryo axis and concomitant with the increase in ammonium content during post-germinative growth. In cotyledons, GDH gene expression was very low. Although in vitro GDH aminating activity was several times higher than its deaminating activity, in vivo 15NH4 incorporation into amino acids was completely inhibited by methionine sulfoximine, a GS inhibitor, indicating that GDH is not involved in ammonium assimilation/detoxification. Changes in the expressions of GS and GOGAT isoforms revealed that GS1b (EC 184.108.40.206) in concert with NADH-dependent GOGAT (EC 188.8.131.52) constitute the major route of assimilation of ammonium derived from reserve mobilization and glutamic acid/glutamine synthesis in germinating M. truncatula seeds. However, during post-germinative growth, although germination was held in darkness, expression of GS2 and Fd-GOGAT (EC 126.96.36.199) increased and expression of GS1b decreased in cotyledons but not in the embryo axis. 2-Oxoglutarate, the substrate of the transamination reaction, was provided by the cytosolic isoform of isocitrate dehydrogenase (EC 188.8.131.52). We suggest that GDH during post-germinative growth, specifically in the developing embryo axis, contributes to ammonium delivery to GS for glutamine synthesis in the absence of primary NO3- assimilation. Interestingly, this reaction also produces reducing power (NADH) in organs deprived of photosynthesis.


Per capita increase in hospital presentations and admissions among children since the 1990s.
Data regarding temporal trends in per capita paediatric hospital presentations and admissions are required to inform health system and workforce planning. Emergency Department (ED) presentations and admissions to the University Hospital Geelong among patients aged 0 to 16 years over a 12-month period (2012-2013) were determined by review of hospital records and then compared with similar data collected during 1996/1997.1 During each period, the Geelong region was serviced by a single ED, enabling us to estimate per capita presentation and admission rates. Since 1996/1997, per capita paediatric presentations to the ED increased from 643 to 1837 per 10 000 (186%; 95% confidence interval 181% to 191%). Moreover, the proportion of paediatric ED presentations resulting in hospital admission increased from 12.3% to 18.3% (49%; 95% confidence interval 39% to 59%). There has been a substantial absolute and per capita increase in paediatric ED presentations and hospital admissions since the 1990s. These trends place an increasing burden on the public hospital system, and strategies are required to promote paediatric acute care in the ambulatory setting.


The expression of KRT2 and its effect on melanogenesis in alpaca skins.
In order to investigate the effects of the keratin 2 (KRT2) on alpaca melanocyte in vivo and vitro, the immunohistochemistry (IHC), quantitative real-time PCR (qPCR), Western blot, and alpaca melanocytes transfection methods were used. The results showed that mRNA and protein expression of KRT2 was highly expressed in brown skin in comparison with that in white skin. Moreover, we found that KRT2 was expressed in alpaca melanocytes in vitro by immunocytochemistry. After transfection with KRT2 in alpaca melanocytes, the relative mRNA and protein expression of KRT2, microphthalmia-associtated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) in alpaca skin melanocytes was increased with significant differences; a further result was the increase of melanin production. The results suggested that KRT2 functions in alpaca hair color formation, which offered an essential theoretical basis for further exploration of the role of melanogenesis.