Antibiotic prescribing: the need for a policy in general practice.
To see whether changes in prescribing of oral antibacterials in Northern Ireland show the need for a community antibiotics policy. Analysis of prescribing totals for several oral antibiotics obtained retrospectively from the prescription pricing bureau for the years 1983-7. Audit of anti-infective prescribing in general practice in Northern Ireland over five years. Respective usage of agents defined as "common" and "occasional" in 1983. There was a gradual decrease in the relative use of common agents from 82% of the total in 1983 to 77% in 1987 together with a complementary increase in the use of occasional agents from 5% to 10%. Pronounced changes were noted in the use of amoxycillin, ampicillin, erythromycin, minocycline, doxycycline, and amoxycillin-clavulanic acid. Though this survey found reasonably conservative prescribing, the trend towards increased use of occasional agents has both clinical and cost implications which could be addressed by the use of a prescribing formulary.


Sacrospinous ligaments anterior apical anchoring for needle-guided mesh is a safe option: a cadaveric study.
To evaluate the feasibility and safety of using the sacro-spinous ligament (SSL) as a fixation point for anterior-apical pelvic floor compartment mesh implants. The apical support achieved with the sacro-spinous ligament mesh fixation is considered adequate, as it provides a high and stronger anchoring point. Even though, meshes for anterior pelvic floor reconstruction are traditionally anchored to the arcus tendineous fascia pelvis (ATFP). The authors presumed that fixing the anterior mesh to the sacro-spinous ligament instead of the ATFP is both feasible and safe. The present study evaluated the anatomical aspects and relations of a modified tissue passage with sacro-spinous fixation of the anterior apical mesh arms. In 5 embalmed female cadavers and 1 fresh female cadaver, the apical arms of the anterior needle-guided mesh were placed through the SSLs rather than through the ATFP, using a transgluteal approach. The distances between the mesh arms and the ureters and uterine arteries were measured. The minimal final distance between the mesh arms and the ureters or uterine arteries was 1.5 cm in the embalmed cadavers, but only 5 mm in the fresh cadaver. However, when analyzing the procedure carefully, it was noted that during dissection the ureters and arteries were pushed medially by the surgeon's finger, thus the operative procedure did not entail any real risk of injury to these structures. The introduced surgical needle caused no trauma to any adjacent cadaveric organs. Anterior pelvic floor meshes may be safely anchored to the SSL, thus potentially improving the apical support.


High-dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation as a treatment option in multiple sclerosis.
High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is a new and promising approach to the treatment of multiple sclerosis (MS) patients because currently there are no effective treatment methods for this disease. In this article, we present results of a prospective clinical study of efficacy of HDIT + auto-HSCT in MS patients. The following treatment strategies were employed in the study: "early," "conventional," and "salvage/late" transplantation. Fifty patients with various types of MS were included in this study. No toxic deaths were reported among 50 MS patients; transplantation procedure was well-tolerated by the patients. The efficacy analysis was performed in 45 patients. Twenty-eight patients achieved an objective improvement of neurological symptoms, defined as at least 0.5-point decrease in the Expanded Disability Status Scale (EDSS) score as compared to the baseline and confirmed during 6 months, and 17 patients had disease stabilization (steady EDSS level as compared to the baseline and confirmed during 6 months). The progression-free survival at 6 years after HDIT + auto-HSCT was 72%. Magnetic resonance imaging data were available in 37 patients before transplantation showing disease activity in 43.3%. No active, new, or enlarging lesions were registered in patients without disease progression. In conclusion, HDIT + auto-HSCT suggests positive results in management of patients with different types of MS. Identification of treatment strategies based on the level of disability, namely "early," "conventional," and "salvage/late" transplantation, appears to be feasible to improve treatment outcomes.


Myocardial effects of alcohol abuse. Clinical and physiologic consequences.
The clinical and physiologic characteristics of alcohol-associated cardiomyopathy are presented. These data presented consist of a review of the signs, symptoms, prognosis, and electrocardiographic and physiologic effects of alcohol administration or use. In addition, the histologic appearance of the heart muscle in alcohol-associated myocardial disease is described.


Increase in S-adenosylhomocysteine concentration in interferon-treated HeLa cells and inhibition of methylation of vesicular stomatitis virus mRNA.
A fraction of the viral mRNA synthesized in interferon-treated HeLa cells infected with vesicular stomatitis virus (VSV) lacks the 7-methyl group in the 5'-terminal guanosine of the cap; this mRNA is not associated with polyribosomes and does not bind to ribosomes in an assay for initiation of protein synthesis (de Ferra, F., and Baglioni, C. (1981) Virology 112, 426-435). To establish whether this defect in methylation is due to changes in the level of the methyl donor S-adenosylmethionine (AdoMet) and of its competitive inhibitor S-adenosylhomocysteine (AdoHcy), we measured the concentration of these compounds in HeLa cells treated with interferon. An increase in both AdoMet and AdoHcy was detected 3 to 6 h after addition of interferon. The level of these compounds increased gradually and in proportion to the interferon concentration used. With 125 reference units/ml of beta interferon, for example, the AdoHcy concentration increased more than 3-fold and that of AdoMet about 1.5-fold with a consequent change in the AdoHcy/AdoMet ratio. An increased AdoHcy/AdoMet ratio was also found in HeLa cells treated with pure alpha 2 interferon produced in Escherichia coli by recombinant DNA techniques. When the methylation of VSV mRNA was measured in assays carried out with permeabilized virions at the AdoHcy and AdoMet concentrations found in interferon-treated cells, a preferential inhibition of the viral (guanine-7-)methyltransferase activity was observed. Such an inhibition may account for the synthesis of VSV mRNA lacking the 7-methyl group of guanosine in the cap.


Financial and medicolegal implications of focused/fast abdominopelvic MRI exams.
Abbreviated MRI offers significant advantages in terms of MRI throughput, patient tolerance and expediency, and is being utilized for a variety of abdominopelvic imaging applications. However questions abound with respect to financial and medicolegal treatment of these relatively new protocols. A review of the relevant literature was performed. There is no Current Procedural Terminology code for a "limited" MRI study, but it may not be appropriate to bill an abbreviated study the same as a more comprehensive study. With respect to medicolegal concerns, the risk of liability when missing or misinterpreting medically significant findings due to use of an abbreviated scan will turn on whether abbreviated MRI has become the standard of care. In light of these ambiguities, it would behoove abdominopelvic imagers to advocate for their professional and subspecialty organizations to issue practice parameters/guidelines with respect to the utilization of abbreviated MRI protocols, and for the subspecialty to bill these abbreviated scans at objectively reasonable rates.


[Active surveillance: concept for renal cell carcinoma?].
More than 80% of renal cell carcinomas are currently being detected incidentally by ultrasonic imaging and often affect elderly patients with substantial comorbidities. Surgical options cannot be applied in this cohort as routinely as in younger patients, as in some cases the perioperative risk factors may outweigh the risk of tumor-related death. In this context the concept of active surveillance for localized renal cell cancer in elderly patients is becoming increasingly important. The aim of active surveillance is to avoid surgery-related adverse effects and to achieve a controlled observation of tumor behavior with an option of delayed intervention in cases of aggressive clinical tumor features. This review sheds light on the current status of this strategy.


In vitro study on effect of bardoxolone methyl on cisplatin-induced cellular senescence in human proximal tubular cells.
Bardoxolone methyl [methyl-2-cyano-3, 12-dioxooleana-1, 9(11)dien-28-oate (CDDO-Me)], an activator of the nuclear factor erythroid-derived 2-related factor2 pathway, is a potential therapeutic candidate for the treatment of kidney diseases. However, its effect against cellular senescence remains unclear. This study aimed to investigate whether CDDO-Me protects cells against cisplatin-induced cellular senescence using an in vitro model. The human renal proximal tubular epithelial cell line HK-2 was treated with cisplatin for 6 h, followed by treatment with or without CDDO-Me (0.1 or 0.2 μmol/L). Senescence markers were analyzed using western blotting and real-time PCR. Apoptosis was evaluated through TUNEL staining. Cisplatin induced changes in the levels of markers specific for proliferation, cell cycle, and senescence in a time- and dose-dependent manner. Furthermore, IL-6 and IL-8 levels in the culture medium increased markedly. These data suggested that cellular senescence-like alterations occurred in HK-2 cells exposed to cisplatin. CDDO-Me treatment reversed the cisplatin-mediated alterations in the levels of cellular senescence markers. The antioxidant enzymes, HO1, NQO1, GPX1, and CAT were upregulated by CDDO-Me treatment. Furthermore, CDDO-Me treatment induced apoptosis in cisplatin-exposed HK-2 cells. Pretreatment with Ac-DEVD-CHO, the caspase inhibitor, suppressed the reversal effect of CDDO-Me against cisplatin-induced cellular senescence-like alterations. This study showed that CDDO-Me attenuated cisplatin-induced premature senescence of HK-2 cells. This beneficial effect may be related to Nrf2 activation. Our findings also showed that CDDO-Me induced apoptosis in cisplatin-treated HK-2 cells, potentially protecting the kidneys from cellular senescence. CDDO-Me appears to be a candidate treatment for acute kidney injury.


Efficacy of propafenone compared with quinidine in chronic ventricular arrhythmias.
A double-blind, randomized study was designed to evaluate the efficacy of oral propafenone and oral quinidine in suppressing premature ventricular complexes (PVCs). Twenty-five men were studied for 3 weeks. Twelve were randomized to the quinidine group and 13 to the propafenone group. Small doses of the drugs were administered for 1 week (200 mg of quinidine every 6 hours or 300 mg of propafenone every 12 hours) and large doses were administered for another week (400 mg of quinidine every 6 hours or 300 mg of propafenone every 8 hours). Strict criteria were used to define responders to antiarrhythmic therapy. For more than 85% reduction in total PVCs per hour: During the low-dose week, 36% in the quinidine group and 50% in the propafenone group were responders (difference not significant [NS]), while during the high-dose week 33% and 64% were responders (NS). For more than 95% reduction of ventricular couplets per hour: During the low-dose week, 45% in each group were responders, while during the high-dose week, 56% and 60% were responders (NS). For 100% abolition of ventricular tachycardia (VT) beats per 24 hours: During the low-dose week, 60% in the quinidine group and 56% in the propafenone group were responders (NS); during the high-dose week 80% and 67% were responders (NS). There was no significant difference in the 2 groups in incidence of side effects. This study shows comparable efficacy and tolerance of propafenone and quinidine for the control of ventricular arrhythmias in ambulatory patients with diverse forms of heart diseases.


Histochemical detection and differentiation of free and esterified cholesterol in swine atherosclerosis using filipin.
The fluorescent probe, filipin, and the lipid-soluble dye, oil red O, have been used to simultaneously detect and differentiate free and esterified cholesterol, respectively, in tissue sections prepared from spontaneous atherosclerotic lesions of swine. This was possible because filipin stains free cholesterol but does not stain cholesteryl ester and because oil red O stains cholesteryl ester but does not stain free cholesterol. Oil red O-stained lipid accumulated intra- and extracellularly but separate from filipin-stained lipid. Spherical filipin-stained particles and elongated filipin-stained crystals accumulated in the extracellular space. Interestingly, some cells appeared to accumulate these filipin-stained particles exclusively. The spherical filipin-stained particles have not been previously recognized because they are not stained by oil red O. This and the fact that extensive compartmentalization of filipin and oil red O-stained lipid occurs in atherosclerotic lesions are new observations to be considered in the pathogenesis of vascular cholesterol accumulation.


Dynactin is essential for growth cone advance.
Dynactin is a multi-subunit complex that serves as a critical cofactor of the microtubule motor cytoplasmic dynein. We previously identified dynactin in the nerve growth cone. However, the function of dynactin in the growth cone is still unclear. Here we show that dynactin in the growth cone is required for constant forward movement of the growth cone. Chromophore-assisted laser inactivation (CALI) of dynamitin, a dynactin subunit, within the growth cone markedly decreases the rate of growth cone advance. CALI of dynamitin in vitro dissociates another dynactin subunit, p150(Glued), from dynamitin. These results indicate that dynactin, especially the interaction between dynamitin and p150(Glued), plays an essential role in growth cone advance.


Transforming bivalent ligands into retractable enzyme inhibitors through polypeptide-protein interactions.
The concept of bivalent polypeptides with controllable flexible linkers is demonstrated through the design of a new generation of 'antidote'-reversible inhibitors of thrombin. These molecules contain two binding moieties, each of which in isolation has only a moderate affinity of binding, which are linked together by a flexible peptide bridge. We show that activities of the potent bivalent inhibitors of thrombin can be reversed by the specific, but much weaker, binding of the linker moiety to protein 'antidotes'.


Remediation of inorganic arsenic in groundwater for safe water supply: a critical assessment of technological solutions.
Arsenic contaminations of groundwater in several parts of the world are the results of natural and/or anthropogenic sources, and have a large impact on human health. Millions of people from different countries rely on groundwater containing As for drinking purposes. This paper reviews removal technologies (oxidation, coagulation flocculation, adsorption, ion exchange and membrane processes) with attention for the drawbacks and limitations of these applied technologies. The technologies suggested and applied for treatment of As rich water have various problems, including the need for further treatment of As containing secondary waste generated from these water treatment processes. More efficient technologies, with a lower tendency to generate waste include the removal of As by membrane distillation or forward osmosis, instead of using pressure driven membrane processes and subsequently reducing soluble As to commercially valuable metallic As are surveyed. An integrated approach of two or more techniques is suggested to be more beneficial than a single process. Advanced technologies such as membrane distillation, forward osmosis as well as some hybrid integrated techniques and their potentials are also discussed in this review. Membrane processes combined with other process (especially iron based technologies) are thought to be most sustainable for the removal of arsenic and further research allowing scale up of these technologies is suggested.


Associations with kidney transplant survival and eGFR decline in children and young adults in the United Kingdom: a retrospective cohort study.
Although young adulthood is associated with transplant loss, many studies do not examine eGFR decline. We aimed to establish clinical risk factors to identify where early intervention might prevent subsequent adverse transplant outcomes. Retrospective cohort study using UK Renal Registry and UK Transplant Registry data, including patients aged < 30 years transplanted 1998-2014. Associations with death-censored graft failure were investigated with multivariable Cox proportional hazards. Multivariable linear regression was used to establish associations with eGFR slope gradients calculated over the last 5 years of observation per individual. The cohort (n = 5121, of whom n = 371 received another transplant) was 61% male, 80% White and 36% had structural disease. Live donation occurred in 48%. There were 1371 graft failures and 145 deaths with a functioning graft over a 39,541-year risk period. Median follow-up was 7 years. Fifteen-year graft survival was 60.2% (95% CI 58.1, 62.3). Risk associations observed in both graft loss and eGFR decline analyses included female sex, glomerular diseases, Black ethnicity and young adulthood (15-19-year and 20-24-year age groups, compared to 25-29 years). A higher initial eGFR was associated with less risk of graft loss but faster eGFR decline. For each additional 10 mL/min/1.73m2 initial eGFR, the hazard ratio for graft loss was 0.82 (95% CI 0.79, 0.86), p < 0.0001. However, compared to < 60 mL/min/1.73m2, higher initial eGFR was associated with faster eGFR decline (> 90 mL/min/1.73m2; - 3.55 mL/min/1.73m2/year (95% CI -4.37, - 2.72), p < 0.0001). In conclusion, young adulthood is a key risk factor for transplant loss and eGFR decline for UK children and young adults. This study has an extended follow-up period and confirms common risk associations for graft loss and eGFR decline, including female sex, Black ethnicity and glomerular diseases. A higher initial eGFR was associated with less risk of graft loss but faster rate of eGFR decline. Identification of children at risk of faster rate of eGFR decline may enable early intervention to prolong graft survival.


LXW7 attenuates inflammation via suppressing Akt/nuclear factor kappa B and mitogen-activated protein kinases signaling pathways in lipopolysaccharide-stimulated BV2 microglial cells.
Microglia activation is closely linked to ischemia, various chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis), and many other central nervous system diseases. Accumulating evidence suggests that depressing the microglial inflammatory response could be an effective treatment for inflammatory disorders. The integrin αvβ3 inhibitor LXW7 has a neuroprotective effect; however, its anti-inflammatory effects and underlying mechanism remain unclear. Thus, we examined whether LXW7 would inhibit inflammatory cytokines and mediators, and we evaluated the potential mechanisms of its neuroprotective effects. Nitrite analysis revealed LXW7 reduced the nitric oxide (NO) level. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) suggested that LXW7 suppressed the expression of proinflammatory genes for tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and anti-inflammatory gene interleukin 10 (IL-10) at the messenger ribonucleic acid level. Enzyme-linked immunosorbent assay results demonstrated that LXW7 treatment reduced the expression of prostaglandin E2 (PGE2), TNF-α, IL-1β and IL-10 at the protein level. Western blotting was conducted to confirm the upregulation of inflammatory factors, including iNOS and COX-2 at the protein level. LXW7 inhibited major genes in the Akt/NF-κB and c-Jun NH2-terminal kinase/ mitogen-activated protein kinases (JNK/MAPK) signaling pathways. Immunofluorescence revealed that LXW7 inhibited the nuclear translocation of nuclear factor kappa B (NF-κB). Thus, LXW7 effectively alleviated LPS-induced inflammatory damage and had neuroprotective effects. The anti-inflammatory effects of LXW7 may be associated with the inhibition of microglial activation via Akt/NF-κB and JNK/MAPK signaling pathways by blocking integrin αvβ3 receptor. The present study's findings suggest that LXW7 has a substantial therapeutic potential for treating inflammatory and neurodegenerative diseases.


Pioglitazone.
Pioglitazone is a thiazolidinedione antidiabetic with actions similar to those of rosiglitazone. It is used in the management of type 2 diabetes mellitus and is prepared by reducing 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzilidene]-2,4-thiazolidinedione with sodium borohydride in the presence of a cobalt ion and dimethyl glyoxime. Ultraviolet spectroscopy shows maximum absorption at 270nm. Infrared spectroscopy shows principal peaks at wave numbers 3082, 2964, 1736, 1690, 1472, 1331, 1254, 1040, 841, 728cm(-1) (KBr disk). The determination method by high-performance liquid chromatography was linear over the range of 25-1500ng/mL of pioglitazone in plasma (r(2)>0.999). The within- and between-day precision values were in the range of 2.4-6.8%. The limit of quantitation of the method was 25ng/mL. It is well absorbed with a mean absolute bioavailability of 83% and reaching maximum concentrations in around 1.5h. It is metabolized by the hepatic cytochrome P450 enzyme system. Following oral administration, approximately 15-30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces.


Assessment of human exposure to environmental sources of lead arising from the lead battery manufacturing and recycling sector in Europe: demonstration of a tiered approach in a case study.
Standard approaches for the assessment of Man via the Environment exposure are designed to be conservative. However, propagating these exposures into health impact assessment might lead to questionable socio-economic costs. The objective of this study was to develop a novel tiered modelling approach to assess human exposure to lead (Pb) via the environment. The approach starts in Tier 1 from EUSES modelling approach, modified with metal specific transfer factors. The generic Tier 2 approach uses the higher tier model GPM for air quality, and dietary exposure modelling based on EFSA's Comprehensive Food Database, in combination with crop specific transfer factors. Tier 3 considers additional site-specific information such as proximity of inhabitants and agricultural activities in relation to industrial sites. This tiered modelling approach was applied to a case study of 50 lead battery manufacturing and recycling sites across Europe. Data sets from general population human biomonitoring studies were used to compare the predicted additional bioburden of Pb resulting from lead battery manufacturing and recycling. The higher tier assessments were able to demonstrate a >20-fold reduction in modelled Pb exposure compared to default assumptions made in Tier 1. Leading to better estimates for socio-economic costs in health impact assessment.


NVAS: A non-interactive verifiable federated learning aggregation scheme for COVID-19 based on game theory.
The continued spread of COVID-19 seriously endangers the physical and mental health of people in all countries. It is an important method to establish inter agency COVID-19 detection and prevention system based on game theory through wireless communication and artificial intelligence. Federated learning (FL) as a privacy preserving machine learning framework has received extensive attention. From the perspective of game theory, FL can be regarded as a process in which multiple participants play games against each other to maximize their own interests. This requires that the user's data is not leaked during the training process. However, existing studies have proved that the privacy protection capability of FL is insufficient. In addition, the existing way of realizing privacy protection through multiple rounds of communication between participants increases the burden of wireless communication. To this end, this paper considers the security model of FL based on game theory, and proposes our scheme, NVAS, a non-interactive verifiable privacy-preserving FL aggregation scheme in wireless communication environments. The NVAS can protect user privacy during FL training without unnecessary interaction between participants, which can better motivate more participants to join and provide high-quality training data. Furthermore, we designed a concise and efficient verification algorithm to ensure the correctness of model aggregation. Finally, the security and feasibility of the scheme are analyzed.


Silent sinus syndrome: potentially misleading features that should be recognized.
Silent sinus syndrome (SSS) usually manifests clinically as hypoglobus and enophthalmos. Patients may experience different symptoms and may present to an assortment of specialties and delay diagnosis and management. The objective of this article was to describe the different and sometimes misleading signs and symptoms of SSS to improve the level of suspicion and reduce time to diagnosis. A retrospective consecutive audit of the records of all patients diagnosed with SSS between 2015 and 2019 in the Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust. Demographic and clinical data including presentation, diagnosis, and symptoms were obtained from the patients' medical files. Ten patients were included; mean age was 42.5 ± 11.5 years (range, 16-56 years). Four patients were initially referred to an ophthalmologist with globe asymmetry, diplopia, eyelid asymmetry, or retraction. Three patients were initially referred to an ear, nose, and throat specialist with facial asymmetry or infraorbital paraesthesia. Two patients were referred from the maxillofacial department with an incidental finding, and the last patient was seen initially by the neurology team with headaches. SSS has a variable presentation. Patients may have common or misleading signs. Patients may attend different clinics and subspecialties, and physicians should be aware of the broad range of presenting signs in this condition to prevent delay in diagnosis and further morbidity.


A Raman, infrared and XRD analysis of the instability in volcanic opals from Mexico.
A series of natural volcanic opal samples with the destabilization phenomena from Mexican deposits (states of Queretaro and Jalisco) was investigated by Raman microprobe (RMP), infrared spectrometry and XRD analysis. These techniques show that at low and room temperatures the unaltered transparent opals may be transformed into destabilized white opals, which are a mixture of different polymorphs of tridymite and alpha-cristobalite with various degrees of crystallinity. We found systematic changes in frequencies of both the Raman and the infrared bands, caused by increasing regularities of bond-lengths and bond-angles Si-O-Si groups under the effect of stability. Micro-Raman spectrometry confirms that in the destabilized opal the principal mineral phases are MC (monoclinic ordered)- and MX (incommensurate monoclinic)-tridymites that are characterized by more structural order in comparison with other structural modification of this phase in unaltered opal (POn pseudo-orthorhombic disordered tridymite). XRD investigations show that in the sequence from unaltered to destabilized opal the position of principal maximum (4.30, 4.10 and 2.50 A) shifts towards higher d-spacing. This XRD shifting to higher d-spacing can largely be explained by an increasing amount of tridymite stacking and unresolved superposition of cristobalite and tridymite reflections. The destabilization phenomena in volcanic opals is due to the structural ordering/disordering that is characterized mainly by the formation of the different tridymite polymorphs (MC and MX) in the destabilized opal-CT as well as the decreasing content of molecular water in the structure.


Epitheloid sarcoma: a case report.
Epitheloid sarcoma of the pulp of the thumb followed repeated penetrating injuries to the digit. It was treated aggressively and successfully to date, nearly 5 years later. In some respects this case report parallels those animal experiments in which foreign body tumorigenesis has been demonstrated, and one might entertain a correlation.


Low-grade duodenal eosinophilia is associated with cagA in Helicobacter pylori-related dyspepsia.
Functional dyspepsia (FD) is a multifactorial disorder. Helicobacter pylori (H. pylori)-related dyspepsia (HpD) may be considered a separate entity. Duodenal eosinophilia is a potential pathogenic mechanism in FD. However, the impact of duodenal eosinophilia and H. pylori virulence genes in HpD was not explored. We aim to evaluate the association of H. pylori virulence genes and low-grade duodenal eosinophilia in HpD. A multi-center cross-sectional study was conducted. A total of 301 patients who meet Rome-III criteria were selected before upper endoscopy, and 95 patients were included after normal endoscopy and positive H. pylori in gastric biopsies were assessed. Clinical parameters, H. pylori virulence genes (cagA, oipA, and vacA) and duodenal histology were evaluated. Sixty-nine (72%) patients had epigastric pain syndrome (EPS), 17 (18%) post-prandial distress syndrome (PDS) and 9 (10%) EPS/PDS overlap. FD syndromes were not associated with cagA or oipA strains. A significantly trend of vacA s1/m1 (78%) and s1/m2 (80%) positive strains in EPS was observed. Histological duodenal grading of chronic inflammation, low-grade duodenal eosinophilia and intra-epithelial lymphocytes showed no difference in oipA and vacA strains. Low-grade duodenal eosinophilia was significant in cagA positive strain, and the OR for low-grade duodenal eosinophilia with H. pylori cagA positive strain was 4.2 (95% CI, 1.78-9.93). Adjusting for age, gender, smoking, diabetes, alcohol, PPI, and NSAID, the OR was 5.44 (1.989-14.902). Our findings suggest that low-grade duodenal eosinophilia is significantly associated with cagA strain in HpD.


Engineering white blood cell membrane-camouflaged nanocarriers for inflammation-related therapeutics.
White blood cells (WBCs) play essential roles against inflammatory disorders, bacterial infections, and cancers. Inspired by nature, WBC membrane-camouflaged nanocarriers (WBC-NCs) have been developed to mimic the "dynamic" functions of WBCs, such as transendothelial migration, adhesion to injured blood vessels, etc, which make them promising for diverse medical applications. WBC-NCs inherit the cell membrane antigens of WBCs, while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent (bio)physicochemical performance. This review summarizes the proposed concept of cell membrane engineering, which utilizes physical engineering, chemical modification, and biological functionalization technologies to endow the natural cell membrane with abundant functionalities. In addition, it highlights the recent progress and applications of WBC-NCs for inflammation targeting, biological neutralization, and immune modulation. Finally, the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.


Cellular iron: ferroportin is the only way out.
Ferroportin is the sole cellular efflux channel for iron and is regulated by the iron regulatory hormone hepcidin, which binds ferroportin and induces its internalization and degradation. New studies of ferroportin knockout mice define a key role for this transporter in physiological iron balance.


COVID-19 and mortality in doctors.
COVID-19 disease appear to have been associated with significant mortality amongst doctors and health care workers globally. We explore the various risk factors associated with this occupational risk, especially focusing on India. This may elucidate lessons to protect these frontline workers during the COVID-19 pandemic. We carried out a comprehensive review of the literature using suitable keywords such as 'COVID-19', 'pandemics', 'physicians' 'mortality' and 'health personnel' on the search engines of PubMed, SCOPUS, Google Scholar and ResearchGate in the month of July 2020 during the current COVID-19 pandemic and assessed mortality data. Mortality in health care professionals has been on the rise. The countries which faced the pandemic in the early months of 2020 have had a huge surge in mortality amongst doctors due to COVID-19. India continues to show a rising trend in COVID-19 cases, however although compared to the western world India has seen a comparatively favourable statistic. Male gender, elderly doctors and those belonging to Black, Asian, and Minority Ethnic (BAME) community seem to be predisposing factors in the western world. COVID-19 has been associated with an increased mortality in doctors and health care workers. Until an effective cure/vaccine is developed, risk assessments at work, mitigating confounding factors, adequate supply of personal protective equipment (PPE) and enhanced protection against infection are necessary to protect health care professionals on the coronavirus frontline. Otherwise this occupational risk can lead to further untimely mortality and become another unintended consequence of the COVID-19 pandemic.


Interaction of ribosomal proteins S6, S8, S15 and S18 with the central domain of 16 S ribosomal RNA from Escherichia coli.
The co-operative interaction of 30 S ribosomal subunit proteins S6, S8, S15 and S18 with 16 S ribosomal RNA from Escherichia coli was studied by (1) determining how the binding of each protein is influenced by the others and (2) characterizing a series of protein-rRNA fragment complexes. Whereas S8 and S15 are known to associate independently with the 16 S rRNA, binding of S18 depended upon S8 and S15, and binding of S6 was found to require S8, S15 and S18. Ribonucleoprotein (RNP) fragments were derived from the S8-, S8/S15- and S6/S8/S15/S18-16 S rRNA complexes by partial RNase hydrolysis and isolated by electrophoresis through Mg2+-containing polyacrylamide gels or by centrifugation through sucrose gradients. Identification of the proteins associated with each RNP by gel electrophoresis in the presence of sodium dodecyl sulfate demonstrated the presence of S8, S8 + S15 and S6 + S8 + S15 + S18 in the corresponding fragment complexes. Analysis of the rRNA components of the RNP particles confirmed that S8 was bound to nucleotides 583 to 605 and 624 to 653, and that S8 and S15 were associated with nucleotides 583 to 605, 624 to 672 and 733 to 757. Proteins S6, S8, S15 and S18 were shown to protect nucleotides 563 to 605, 624 to 680, 702 to 770, 818 to 839 and 844 to 891, which span the entire central domain of the 16 S rRNA molecule (nucleotides 560 to 890). The binding site for each protein contains helical elements as well as single-stranded internal loops ranging in size from a single bulged nucleotide to 20 bases. Three terminal loops and one stem-loop structure within the central domain of the 16 S rRNA were not protected in the four-protein complex. Interestingly, bases within or very close to these unprotected regions have been shown to be accessible to chemical and enzymatic probes in 30 S subunits but not in 70 S ribosomes. Furthermore, nucleotides adjacent to one of the unprotected loops have been cross-linked to a region near the 3' end of 16 S rRNA. Our observations and those of others suggest that the bases in this domain that are not sequestered by interactions with S6, S8, S15 or S18 play a role involved in subunit association or in tertiary interactions between portions of the rRNA chain that are distant from one-another in the primary structure.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of lipolytic agents on adenosine and AMP formation by fat cells.
The release and metabolism of adenosine was examined using rat fat cells in which the nucleotide pool has been labeled by incubation with radioactive adenine. The accumulation of adenosine in the medium was near maximal at the start of the incubation and increased only slightly thereafter. Adenosine was rapidly deaminated to inosine and subsequently oxidized to uric acid. In the presence of allopurinol, and inhibitor of xanthine dehydrogenase, hypoxanthine accumulated in the medium as the end-product of adenosine catabolism. Adenosine accumulated in the medium only if fat cells were incubated in the presence of erythro-9-(2-hydroxy-3-nonyl)adenine, an inhibitor of adenosine deaminase. Even in the presence of this inhibitor there was no acceleration of adenosine release by norepinephrine in the presence of theophylline. However, there was an increase in labeled intracellular AMP accumulation by norepinephrine plus theophylline. The increase in labeled AMP correlated with the final free fatty acid to albumin ratio suggesting that the rise in AMP was related to an accumulation of intracellular free fatty acids. The addition of sodium oleate to the medium mimicked the effect of norepinephrine plus theophylline on the accumulation of labeled AMP. These results indicate that AMP rather than adenosine accumulates in isolated fat cells during incubation with lipolytic agents.


[Reduced incidence of side-effects of growth hormone substitution in 404 patients with hypophyseal insufficiency. Results of a multicenter indications study].
Substitution of pituitary insufficient patients with recombinant human growth hormone (rhGH) in addition to the conventional substitution with glucocorticoids, L-thyroxine and sex hormones has been approved by the regulatory authorities in 1995 with the imposition to conduct surveillance studies to monitor drug safety. 24% of all patients were within their 2nd treatment year, 15% within their 4th year, maximum treatment period was 6 years. There were 2 peaks within the patients age distribution: 30 to 39 years (24%) and 50 to 59 years (24%). The causes for pituitary disease were as follows: pituitary adenomas (47%), idiopathic (16%), craniopharyngeomas (16%) and others (21%). Mean GH dose was 1.5 IU/d s.c. (range 0.4 to 4 IU/d). Serum-IGF-1 increased by 159 and 192% in females and males. Waist circumference decreased by 2% and serum cholesterol was lowered by 5.5% in males. There were 2 cases with new carcinomas, 1 diabetes mellitus II and 1 death. Adverse events (AEs) within KIMS were compared to those of the treatment (GH) and placebo (PI) groups of the previous admission trials (in percent): edema: KIMS 10, GH 37, Pl 3; arthralgia: KIMS 8, GH 19, Pl 2; muscle pain: KIMS 3, GH 16, Pl 3; dizziness: KIMS 2, GH 1, Pl 3; headache: KIMS 2, GH 3, Pl 2; others: KIMS 2, GH 22, Pl 13. The reported incidence of AEs in KIMS was lower than in previous clinical trials. There might be 3 reasons for this: 1. under-reporting, particularly those AEs not likely to be related to GH treatment; 2. doses used in trials were 2-fold higher than in KIMS; 3. dose titration for individual patients. Surveillance programs are important for monitoring of drug long-term efficacy and safety.


Mitsunobu alkylation of cancerostatic 5-fluorouridine with (2E)-10-hydroxydec-2-enoic acid, a fatty acid from royal jelly with multiple biological activities.
5-Fluorouridine (1) - a nucleoside antimetabolite with strong cancerostatic properties - was protected i) at the 2'- and 3'-OH groups with a heptan-4-ylidene residue and ii) at the 5'-OH group with a (4-methoxyphenyl)(diphenyl)methyl residue. This fully protected compound, 3, was submitted to a Mitsunobu reaction with the N-hydroxysuccinimide (NHS) ester, 5, of (2E)-10-hydroxydec-2-enoic acid (4) which gave nucleolipid 6. The latter was detritylated with Cl2 CHCOOH to yield the co-drug 7 as NHS ester.


Prenatal ultrasonographic findings may be useful in predicting the prognosis of trisomy 18.
This study was conducted to determine whether specific ultrasonographic findings in the prenatal period were associated with survival of children affected with trisomy 18. Between October 1987 and July 2004, we collected 24 cases with trisomy 18. We investigated the relationship of prenatal ultrasonographic findings, gestational age at delivery, the Apgar score, the mode of delivery, and the neonatal treatment strategies, with survival time. 17 of the 24 neonates died within 1 month after birth (Group 1), 5 died within 12 months (Group 2), and 2 survived for more than 1 year (Group 3). Severe polyhydramnios was more frequent in group 1. In groups 2 and 3, the fluid in fetal stomach was visible in all cases. Severe cardiac anomalies were more frequent in group 1. In groups 2 and 3, all neonates were girl. Prenatal ultrasonographic findings associated with survival less than 1 month included severe polyhydramnios, absence of the fluid in the stomach, severe cardiac anomaly and male sex.


Bioavailability enhancers of herbal origin: an overview.
Recently, the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines. However, many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size, resulting in poor absorption and hence poor bioavailability. Nowadays with the advancement in the technology, novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems. For last one decade many novel carriers such as liposomes, microspheres, nanoparticles, transferosomes, ethosomes, lipid based systems etc. have been reported for successful modified delivery of various herbal drugs. Many herbal compounds including quercetin, genistein, naringin, sinomenine, piperine, glycyrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability. The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs (herbal), and to achieve better therapeutic response. An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action (wherever reported) and studies on improvement in drug bioavailability, exhibited particularly by natural compounds.


The prognostic significance of SYNTAX score after early percutaneous transluminal coronary angioplasty for acute ST elevation myocardial infarction.
SYNergy between percutaneous coronary intervention (PCI) with TAXUS and Cardiac Surgery (SYNTAX) score, which is based on the characteristics of atherosclerotic lesions and the complexity of coronary artery anatomy, is useful for choosing an intervention strategy, but its prognostic significance for acute ST elevation of myocardial infarction (STEMI) remains unknown. This study aimed to redress this issue. Our observational study included 151 consecutive patients admitted for acute STEMI who underwent primary PCI between January 1, 2008 and December 31, 2009. The primary endpoint for analysis was 30-day cardiac death. Among the 151 patients, cardiac death occurred in 10 (7%) within 30 days. After the first month, five patients died of non-cardiac causes, but no cardiac death occurred. Multivariate analysis showed that SYNTAX score (odds ratio [OR], 13.79, 95% confidence interval [CI], 1.24-153.38; p=0.033) and a symptom onset-to-therapy time interval >4 h (OR, 11.13; 95% CI, 1.08-114.42; p=0.043) were independent risk factors for 30-day mortality. The SYNTAX score cut-off for discriminating low and high risk was 22. SYNTAX score is an independent predictor of short-term cardiac mortality in patients with acute STEMI.


Acellular nerve xenografts based on supercritical extraction technology for repairing long-distance sciatic nerve defects in rats.
Compared to conventional artificial nerve guide conduits (NGCs) prepared using natural polymers or synthetic polymers, acellular nerve grafts (ACNGs) derived from natural nerves with eliminated immune components have natural bionic advantages in composition and structure that polymer materials do not have. To further optimize the repair effect of ACNGs, in this study, we used a composite technology based on supercritical carbon dioxide (scCO2) extraction to process the peripheral nerve of a large mammal, the Yorkshire pig, and obtained an innovative Acellular nerve xenografts (ANXs, namely, CD + scCO2 NG). After scCO2 extraction, the fat and DNA content in CD + scCO2 NG has been removed to the greatest extent, which can better supported cell adhesion and proliferation, inducing an extremely weak inflammatory response. Interestingly, the protein in the CD + scCO2 NG was primarily involved in signaling pathways related to axon guidance. Moreover, compared with the pure chemical decellularized nerve graft (CD NG), the DRG axons grew naturally on the CD + scCO2 NG membrane and extended long distances. In vivo studies further revealed that the regenerated nerve axons had basically crossed the CD + scCO2 NG 3 weeks after surgery. 12 weeks after surgery, CD + scCO2 NG was similar to autologous nerves in improving the quality of nerve regeneration, target muscle morphology and motor function recovery and was significantly better than hollow NGCs and CD NG. Therefore, we believe that the fully decellularized and fat-free porcine ACNGs may be the most promising "bridge" for repairing human nerve defects at this stage and for some time to come.


Laser-Capture Microdissection of Maize Kernel Compartments for RNA-Seq-Based Expression Analysis.
Laser-capture microdissection (LCM) enables isolation of single cells or groups of cells for a variety of downstream applications including transcriptome profiling. Recently, this methodology has found a more widespread use particularly with the advent of next-generation sequencing techniques that enable deep profiling of the limited amounts of RNA obtained from fixed or frozen sections. When used with fixed tissues, a major experimental challenge is to balance the tissue integrity needed for microscopic visualization of the cell types of interest with that of the RNA quality necessary for deep profiling. Complex biological structures such as seeds or kernels pose an especially difficult case in this context as in many instances the key internal structures such as the embryo and the endosperm are relatively inaccessible. Here, we present an optimized LCM protocol for maize kernel that has been developed specifically to enable profiling of the early stages of endosperm development using RNA-Seq.


Stem cells, evolutionary aspects and pathology of the adrenal medulla: A new developmental paradigm.
The mammalian adrenal gland is composed of two main components; the catecholaminergic neural crest-derived medulla, found in the center of the gland, and the mesoderm-derived cortex producing steroidogenic hormones. The medulla is composed of neuroendocrine chromaffin cells with oxygen-sensing properties and is dependent on tissue interactions with the overlying cortex, both during development and in adulthood. Other relevant organs include the Zuckerkandl organ containing extra-adrenal chromaffin cells, and carotid oxygen-sensing bodies containing glomus cells. Chromaffin and glomus cells reveal a number of important similarities and are derived from the multipotent nerve-associated descendants of the neural crest, or Schwann cell precursors. Abnormalities in complex developmental processes during differentiation of nerve-associated and other progenitors into chromaffin and oxygen-sensing populations may result in different subtypes of paraganglioma, neuroblastoma and pheochromocytoma. Here, we summarize recent findings explaining the development of chromaffin and oxygen-sensing cells, as well as the potential mechanisms driving neuroendocrine tumor initiation.


Testicular lymphoma: a literature review and report of a case with a zoster-like cutaneous recurrence.
Testicular lymphoma accounts for approximately 1% of all cases of non-Hodgkin's lymphoma. This distinct clinical entity can have an aggressive course with a high rate of systemic relapse. We describe a unique case of a diffuse large B-cell lymphoma, T-cell-rich variant with cutaneous dermatomal zosteriform recurrence presenting as neuralgia. This case represents a unique pattern of treatment failure in this aggressive extranodal lymphoma.


Bone quality: a determinant for certain risk factors for bone fragility.
Low bone quantity alone is insufficient cause for fragility fractures. This paper examines the role of bone quality in the fracture risk associated with age, sex, and race. Aspects of bone quality to be considered are bone architecture, matrix, mineralization, and fatigue damage. The trabecular network becomes progressively disconnected and weaker with age. Death of old osteocytes leads to hypermineralization and brittleness of bone. The stability of bone collagen declines with age, and unremodeled bone accumulates fatigue damage. The lower bone fragility rates in males than in females may be due to a combination of the larger male skeleton, greater cortical bone density after age 60 years, and greater bone turnover which would replace fatigue damaged bone. Fragility fracture rates in American and African blacks are lower than in whites, bone mineral density (BMD) is greater in American but not in African blacks (except for hip BMD), and American blacks have lower and African blacks higher bone turnover compared to whites. In South African blacks, trabeculae are thicker and better connected and trabecular bone undergoes less destructive age changes than in whites. To reconcile the disparate findings in American and African blacks we suggest that both groups have a genetic tendency to greater BMD than whites; American blacks realize this potential and African blacks do not, possibly because of calcium deficiency. Consequent high turnover removes fatigue damage and so improves bone quality. Weight-bearing activity in African blacks may be responsible for good hip bone density and thick trabeculae.(ABSTRACT TRUNCATED AT 250 WORDS)


Metformin as a radiosensitiser for pelvic malignancy: A systematic review of the literature.
The treatment of pelvic malignancies has continued to improve over recent years, with neoadjuvant radiotherapy often considered the gold standard to downstage disease. Radiosensitisers are routinely employed in an attempt to improve response of cancers to radiotherapy. Previous preclinical evidence has suggested a role for metformin, a commonly used drug for type 2 diabetes. A literature search was performed for published full text articles using the PubMed, Cochrane and Scopus databases using the search criteria string 'Metformin' AND ('Radiosensitivity' OR 'radiosensitising' OR 'radiosensitising'). Additional papers were detected by scanning the references of relevant papers. Data were extracted from each study by two authors onto a dedicated proforma. The review was registered on the PROSPERO database (ID: CRD42020199066). A total of 242 papers were identified, 11 of which were included in this review; an additional 5 papers were obtained from reference searches. Metformin has been demonstrated to reduce cell-viability post-radiotherapy in both rectal and prostate cancer cell lines, with an enhanced effect in tumours with a p53 mutation and increased apoptosis post-radiotherapy for cervical cancer. Clinical trials demonstrate improved tumour and nodal downstaging and pCR rates for rectal cancer using metformin as a radiosensitiser. With an increasing understanding of the underlying mechanism of the effects on metformin prospective studies are required to assess the effect of routine use on cancer related outcomes. Progressive future studies may be better served by the use of predictive biomarker guided treatment to enable identification of the appropriate cohort to target.


Quality of life issues in psoriasis.
Psoriasis is associated with significant psychosocial morbidity and a decrease in health-related quality of life. It is important to view psoriasis as a serious disease and resist the tendency to underestimate its impact on overall patient well-being. The disability experienced by psoriasis sufferers is comparable to that of patients with other chronic illnesses such as heart disease, diabetes, cancer, and depression. Aggressive intervention is warranted in order to improve patient quality of life and decrease the potential for psychosocial sequelae. Health-related quality of life measures are becoming a necessary adjunct to traditional clinical assessments in the evaluation and treatment of psoriasis patients by the individual clinician. They also provide valuable information to government agencies and third party payers in the determination of resource allocation and reimbursement.


Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome.
We previously demonstrated that constitutional BUB1B mutations cause mosaic variegated aneuploidy, a condition characterized by constitutional aneuploidies and childhood cancer predisposition. To further investigate the role of BUB1B in cancer predisposition we performed comparative genomic hybridization analysis in an embryonal rhabdomyosarcoma from an MVA case with biallelic BUB1B mutations, revealing aneuploidies typical of sporadic E-RMS, with gain of chromosomes 3, 8, 13 and loss of chromosomes 9, 14, X. To investigate whether somatic BUB1B mutations occur in sporadic childhood cancers we screened 30 Wilms tumours, 10 acute lymphoblastic leukemias, nine rhabdomyosarcomas and 11 rhabdomyosarcoma cell lines for BUB1B mutations. We identified seven exonic and six intronic variants. Six of the exonic variants were synonymous and one resulted in a non-synonymous conservative missense alteration that was also present in a control. These data suggest that the genetic progression in rhabdomyosarcoma from MVA and non-MVA cases may be similar, but that somatic BUB1B mutations are unlikely to be common in sporadic childhood cancers known to be associated with MVA.


Aphaereta pallipes (Hymenoptera: Braconidae) and Dirhinus anthracia (Hymenoptera: Chalcididae) associated with Peckia (Euboettcheria) collusor (Diptera: Sarcophagidae) in Brazil.
Flies of the Sarcophagidae family are widely distributed in the world, occupying different habitats. Some species have a high degree of synanthropy and are therefore often found in households in the urban environment. In Brazil, there is still little information related to the natural enemies of these insects in the urban environment, where population control is strictly chemical. Therefore, larvae and pupae of Peckia (Euboettcheria) collusor (Curran and Walley) (Diptera: Sarcophagidae) species were exposed in an urbanized location, and the presence and prevalence of parasitoids in the natural control of these immature stages was evaluated. We report for the first time the species Aphaereta pallipes (Say) (Hymenoptera: Braconidae) and Dirhinus anthracia Walker (Hymenoptera: Chalcididae), associated with P. (E.) collusor, highlighting the importance of these parasitoids in natural control in the urban environment, in addition to expanding the list of hosts for both parasitoid species and the distribution of this parasitoid-host interaction for Brazil and the Neotropical region.


Combinatorial protein engineering and transporter engineering for efficient synthesis of L-Carnosine in Escherichia coli.
L-Carnosine has various physiological functions and is widely used in cosmetics, medicine, food additives, and other fields. However, the yield of L-Carnosine obtained by biological methods is far from the level of industrial production. Herein, a cell factory for efficient synthesis of L-Carnosine was constructed based on transporter engineering and protein engineering. Firstly, a dipeptidase (SmpepD) was screened from Serratia marcescens through genome mining to construct a cell factory for synthesizing L-Carnosine. Subsequently, through rationally designed SmPepD, a double mutant T168S/G148D increased the L-Carnosine yield by 41.6% was obtained. Then, yeaS, a gene encoding the exporter of L-histidine, was deleted to further increase the production of L-Carnosine. Finally, L-Carnosine was produced by one-pot biotransformation in a 5 L bioreactor under optimized conditions with a yield of 133.2 mM. This study represented the highest yield of L-Carnosine synthesized in microorganisms and provided a biosynthetic pathway for the industrial production of L-Carnosine.


Current trends in Candida albicans research.
Candida albicans is an opportunistic pathogen of human beings and other mammals. Two other features, besides its pathogenicity, have made it a popular organism of study. It exists in different cellular forms and can change from one form to another, depending on growth conditions. Thus, it is being used as a model system to study cellular differentiation. It can also heritably and reversibly switch its cellular and colony morphologies. The yeast is diploid and lacks a sexual cycle. Thus, it has not been possible to apply the powerful methods of genetic analysis to understand morphogenesis or pathogenesis. Few clinical isolates are haploid, but they do not form hyphae and are not yet well characterized. Recombinant DNA techniques are increasingly being applied to C. albicans to solve many of the unanswered questions of morphogenesis and pathogenesis. Genetic transformation and gene-disruption techniques were recently developed for the yeast. Thus it is possible to study the role of any cloned gene through directed mutagenesis. However, the difficulty is to clone the putative genes involved in morphogenesis or pathogenesis. Candida albicans exists in four different cellular forms, namely blastospores, pseudohyphae, hyphae and chlamydospores. Blastospore-to-hypha conversion is well studied. A variety of conditions can induce this transition. It is not clear how cells sense such varied conditions and respond appropriately. In other systems where differentiation is well understood, regulatory genes which control differentiation have been uncovered. These genes cause differential expression of other genes, and ultimately differentiated phenotypes. Thus, it is likely that differential gene expression is involved in the bud-to-hypha transition in C. albicans. Certain proteins are expressed exclusively on the cell surface of hyphae. It should be possible to clone genes coding for these proteins. A study of the expression of these genes might allow us to identify the regulatory gene which determines differentiation. Another approach to understanding morphogenesis is to study how the difference in the shape of buds and hyphae is generated. This difference appears to be due to the differential activity of apical and general growth zones, which determine growth of the cell wall. Activity of these growth zones is apparently determined by actin localization. It remains a possibility that conditions which induce hyphae formation may directly affect actin localization or cell-wall growth zones and cause differences in cell shape. Candida albicans can also heritably switch its cellular phenotype. This has come to light from a study of colony-morphology switching. Some strains can switch their colony morphology, both heritably and reversibly.(ABSTRACT TRUNCATED AT 400 WORDS)


Gold Rods Irradiated with Ultrasound for Combination of Hyperthermia and Cancer Chemotherapy.
The aim of this study was to analyze feasibility (in vitro and in vivo) the use of hyperthermia produced by gold rods irradiated with ultrasound and their combination with chemotherapy with doxorubicin. initially was determined the cell viability and Hsp70 levels after treatment by gold rods irradiated with ultrasound (GR+U) in cell culture. The pretreatment with GR+U combined with doxorubicin (DOX) was evaluated from IC50, caspase-3 expression and mechanisms of cell death by electron microscopy. For evaluate the in vivo effects was used solid Ehrlich carcinoma (SEC) Tumor. The animals received three treatments with the combination of GR+U+DOX over 16 days. The cell viability was completely inhibited after 40 min of treatment with GR+U and significant increases the expression of HSP70 was only observed after 10 min of treatment. GR+U+DOX presented significant reduction of IC50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. GR+U+DOX presented significant reduction of IC50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. The caspase-3 level and ultraestructural analysis showed that treatment with GR+U+DOX enhances induction of apoptosis. Pretreatment with GR+U combined with doxorubicin (1 mg) showed 87% inhibition against SEC. and no showed cardiotoxic effect. The combined treatment of GR+U and DOX exhibit synergistic characteristics observed by increasing the efficiency of doxorubicin.


[Quality evaluation of polysaccharide of ginseng injections from different manufacturers].
To evaluate injections of ginseng polysaccharide from 4 different manufacturers of 5 batches on the market. Based on quality analysis, normal examinations were investigated, and monosaccharide composition and the molecular weight of polysaccharide in ginseng injections were performed. Products from 4 different manufacturers were in line with the requirements of quality standard and Chinese Pharmacopeia (2010 edition). But there were great differences in molecular weight and monosaccharide composition. It is suggested to enhance the quality standard to ensure the medication safety use.


A flavonoid-based fluorescent probe enables the accurate quantification of human serum albumin by minimizing the interference from blood lipids.
We herein provide a simple design strategy to improve the sensing specificity towards human serum albumin by incorporating a nitrobenzene quencher into a traditional polarity-sensitive probe in responding to the interference from blood lipids.


Sodium valproate induced alterations in monoamine levels in different regions of the rat brain.
Sodium valproate is a well established anticonvulsant drug but its exact mode of action is not yet clear. With a view to find out whether the mechanism of action of sodium valproate is mediated by alteration in monoamine levels, apart from GABA, in brain, sodium valproate (200 mg/kg body wt) was administered i.p. to male adult Wistar rats for 45 days. The levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were assayed in different brain regions using high performance liquid chromatographic (HPLC) method. It was noted that at the end of the experimental period there was no change in body or brain weight nor were there any neurological deficits as a result of sodium valproate administration. However, after administration of sodium valproate there was a significant increase in norepinephrine levels in hippocampus (P < 0.01) and brainstem (P < 0.01) while a significant decrease was noted in hypothalamus (P < 0.001). Dopamine levels were significantly increased in motor cortex (P < 0.01), hippocampus (P < 0.01) and hypothalamus (P < 0.001). Serotonin levels were significantly increased in striatum-accumbens and brain stem (P < 0.001). However a marginal increase was also observed in motor cortex and hippocampus. 5-HT levels were significantly decreased in hypothalamus (P < 0.001) and cerebellum (P < 0.01). The present findings suggest the possibility that the anticonvulsant effect of sodium valproate could be due to alterations in monoamine levels apart from its action on GABA, which would indicate also the efficacy of this drug in different types of seizures.


Postnatal development of the glycine cleavage system in rat liver.
The development of the glycine cleavage system was studied in liver mitochondrial extracts from neonatal and adult rats. The enzyme activity in 2-day-old pups was 29.3% of that measured in the adult and was found to increase in an age-dependent manner. Measurement of hepatic free amino acid concentrations at the neonatal ages showed that glycine levels were highest at 2 days and at 14 days were about 48% of those in the 2-day-old pups. Serine levels did not change between the age of 2 and 14 days. A developmental delay in the glycine cleavage system is responsible for the high levels of glycine in the neonatal rat liver.


Overexpression of Bmhsp19.9 protects BmE cells and transgenic silkworm against extreme temperatures.
Temperature stress disrupts protein homeostasis in biological cells. High temperature causes death of the silkworm Bombyx mori, while low temperature leads to slow growth of silkworm in sericulture. Small heat shock proteins (sHsps) play a crucial role in maintaining protein homeostasis and protecting cells against various harmful conditions. In this study, the expression patterns of Bmhsp19.9 were analyzed by reverse transcription (RT)-PCR and quantitative PCR. The promoters hsp19.9P1 and hsp19.9P2 of Bmhsp19.9 were cloned, quantitative PCR and western blotting confirmed that the longer promoter of hsp19.9P1 showed higher activity compared to hsp19.9P2. Overexpression of Bmhsp19.9 increased the viability of BmE cells at high temperatures. The transgenic vector pb-H19.9 was constructed, in which Bmhsp19.9 was overexpressed under the control of hsp19.9P1. Two transgenic lines, H19.9A and H19.9B, were generated via microinjection of P50 silkworm embryos. Quantitative PCR and western blotting revealed that the content of Bmhsp19.9 in transgenic silkworms was higher than that in the control. After exposure to 35 °C for 49 h, the survival rate was increased by approximately 40% in transgenic silkworms compared to non-transgenic P50. When P50 and H19.9A were reared at 13 °C, growth was faster and the survival rate and surviving larval weight were significantly higher in H19.9A compared to P50. These results suggest that overexpression of Bmhsp19.9 increased the resistance of transgenic silkworms to extreme temperatures, which may be useful for sericulture in regions and seasons with no optimal average temperatures for silkworm.


Quantitative evaluation of the microjet velocity and cavitation erosion on a copper plate produced by a spherical cavity focused transducer at the high hydrostatic pressure.
Cavitation erosion at the high hydrostatic pressure causes the equipment to operate abnormally for the huge economic losses. Few methods can quantitatively evaluate the cavitation erosion intensity. In order to solve this problem, the cavitation erosion on a copper plate was carried out in a spherical cavity focused transducer system at the hydrostatic pressure of 3, 6, and 10 MPa. Meanwhile, the corresponding cavitation threshold, the initial bubble radius, and the microjet velocity in the ultrasonic field are theoretically analyzed to determine the dimension and velocity of microjet based on the following hypotheses: (1) the influence of the coalescence on the bubble collapse is ignored; (2) the dimension of the microjet is equal to the largest bubble size without the influence of gravity and buoyancy. Using the Westervelt equation for the nonlinear wave propagation and the Johnson-Cook material constitutive model for the high strain rate, a microjet impact model of the multi-bubble cavitation was constructed. In addition, through the analogy with the indentation test, an inversion model was proposed to calculate the microjet velocity and the cavitation erosion intensity. The microjet geometric model was constructed from the dimension and velocity of the microjet. The continuous microjet impact was proposed according to the equivalent impact momentum and solved by the finite element method. The relative errors of the pit depth are 4.02%, 3.34%, and 1.84% at the hydrostatic pressure of 3, 6, and 10 MPa, respectively, and the relative error in the evolution of pit morphology is 7.33% at 10 MPa, which verified the reliability of the proposed models. Experimental and simulation results show that the higher the hydrostatic pressure, the greater the pit depth, pit diameter, the pit-to-microjet diameter ratio, and the cavitation erosion intensity, but the smaller the pit diameter-to-depth ratio. The cavitation erosion intensity becomes significant with the ongoing ultrasonic exposure. In addition, a comparison of the cavitation pit morphology in the microjet pulsed and continuous impact modes shows that the continuous impact mode is effective without the elastic deformation caused by the residual stress. Using the cavitation pit morphology at the different hydrostatic pressures, the microjet velocity can be estimated successfully and accurately in a certain range, whose corresponding errors at the lower and upper limit are 5.98% and 0.11% at 3 MPa, 6.62% and 9.14% at 6 MPa, 6.54% and 5.42% at 10 MPa, respectively. Our proposed models are valid only when the cavitation pit diameter-to-depth ratio is close to 1. Altogether, the cavitation erosion induced by multi-bubble collapses in the focal region of a focused transducer could be evaluated both experimentally and numerically. Using the cavitation pit morphology and the inversion model, the microjet velocity in a certain range could be estimated successfully with satisfactory accuracy.


Isoelectric focusing of horse serum esterase isozymes and detection of new phenotypes.
A new method for separating the isozymes of horse serum esterase is described. The improved resolution has enabled us to detect several previously undescribed phenotypes. This method has also been used to detect two different apparently 'silent' alleles.


Formal mentorship in Canadian radiology residency programmes.
To characterise formal mentorship programmes in Canadian radiology residency programmes, to evaluate residents' perspectives on formal mentorship, and to identify ways to optimise mentorship during radiology training. An anonymous survey was distributed to radiology resident representatives of the Canadian Association of Radiologists (CAR) Resident and Fellow Section (RFS). Questions pertained to the presence and structure of formal mentorship programmes at each participant's institution. The survey was distributed to 33 radiology residents, of which 30 responded. All 16 accredited radiology residency programmes in Canada were represented. Of these programmes, 12 (75%) had formal mentorship programmes and four (25%) did not. The structure of formal mentorship programmes varied among institutions including one-on-one and group mentoring. For 33% of residency programmes, the programme director assigned the mentor and mentee groups. Only 33% of respondents had the option of choosing their mentor. Lack of funding and lack of time were the two main perceived barriers by residents to maintaining mentorship relationships. Although not all radiology residency programmes in Canada have a formal mentorship programme, most have a form of structured mentorship in place. As formal mentorship programmes improve overall mentorship experience during residency, they can lead to improved research productivity, fellowship, and career preparation, as well as work-life balance for Canadian radiology residents.


Oculomotor and skeletal motor systems share one map of visual space.
Previous research has shown that cognitive and motor visual systems have separate maps of visual space because spatial values in them can be manipulated independently. Here we ask whether the motor map in turn can be divided into separate representations of space. Forty large saccadic eye movements in darkness resulted in significant ocular undershoot of a remembered eccentric target location, and a comparable amount of undershoot with manual pointing to the same remembered target. Saccadic and manual measures were also highly correlated within sessions as well as between sessions. Because pointing could be changed by manipulating only saccades, we conclude that the two systems share a single map of space.


Impact of salinity on anaerobic ceramic membrane bioreactor for textile wastewater treatment: Process performance, membrane fouling and machine learning models.
Anaerobic membrane bioreactor (AnMBR) shows great potential for textile wastewater treatment, but high salinity in the influent may undermine its performance. This study evaluated the impact of salinity on the treatment performance of an upflow anaerobic sludge blanket (UASB) configured AnMBR using a flat sheet ceramic membrane. The salinity was stepwise increased (0, 5, 10 and 20 g/L) in four phases of the AnMBR operation. Results indicated that increased salinity jeopardized the COD removal efficiency of AnMBR from 92% to 73%, but had a marginal effect on dye removal efficacy (90-96%). Low salinity (5 g/L) boosted the biogas production whilst high salinity (>10 g/L) had a negative impact. Additionally, the increase of salinity resulted in the soluble microbial production (SMP) concentration soar and membrane fouling rate increase, peaking at a salinity of 10 g/L (Phase III) and recovering back to a lower level at a salinity of 20 g/L (Phase IV). This indicated a transition occurrence at a salinity of 10 g/L (Phase III). The microbial diversity analyses further suggested a transition from salinity-sensitive microbes (Aminiphilus, Caldatribacterium, Mesotoga, Methanobrevibacter, Methanobacterium, Methanosaeta) to salinity-tolerant microbes (Longilinea, Ignavibacterium, Rhodovarius, Bosea and Flexilinea). This transition can be associated with the increase SMP concentration and more severe membrane fouling in Phase III, which were mitigated after a new equilibrium was reached when the microbial consortium acclimatized to the high salinity. Finally, a machine learning model of the Adaboost algorithm was established to predict COD removal under different salinities. Importantly, this study revealed that AnMBR process performance and membrane operation can be maintained for high salinity textile wastewater treatment with a halophilic microbial community growth under high-salinity selection pressure.


Correction to: LIN28B increases neural crest cell migration and leads to transformation of trunk sympathoadrenal precursors.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


A metabolomics discrimination-based strategy for screening the antithrombin active markers of perilla seeds: A natural oil crop.
Natural crops oil with high nutritional value has gradually attracted attention. Perilla seeds are regarded as a source of functional edible oil in America, Asia and European countries due to its abundant nutrients. In this research, samples were extracted by different polarity solvents and evaluated their thrombin inhibition activities in vitro. Metabolomics combined with chemometrics revealed the antithrombin active markers of perilla seeds. The enzyme kinetics and molecular docking results were useful in clarifying their inhibition of thrombin. The orthogonal experimental design was applied to optimize the extraction process of six antithrombin active markers from perilla seeds. The results showed that rosmarinic acid, luteolin, luteolin-7-O-glucoside, α-linolenic acid, linoleic acid, and oleic acid were screened out as functional and active markers. Besides, perilla seeds as a natural oil crop had the potential of antithrombin. It can also be applied in the food field because of its nutraceutical functions. Metabolomics combined with chemometrics will facilitate the discovery of functional, active markers in perilla seeds, which is conducive to accurate quality control.


Lignin from bamboo shoot shells as an activator and novel immobilizing support for α-amylase.
This study examined the feasibility of α-amylase activation and immobilization, using lignin from bamboo shoot shells (BSS). Our results demonstrated that BSS lignin is an excellent α-amylase activator and it elevated α-amylase activity more than two-fold at a concentration of 5mg/ml. For immobilization of α-amylase via adsorption, BSS lignin was incubated in an α-amylase solution (5mg/ml) for 20min, and the maximum specific activity, amount of loaded protein and activity recovery were 92.4U/mg, 19.0mg/g and 111%, respectively. In contrast to its free counterpart, immobilized α-amylase improved the catalytic efficiency and storage stability, under comparable working conditions (temperature and pH). Regarding its convenient usage, immobilized enzyme can be suspended in advance, but a suspension incubated at 60°C should be used within 30min. The residual activity after 14 re-uses remained at a reasonable level (53.2%). In conclusion, this study reveals a novel support for enzyme immobilization.


SrCe0.9Sm0.1O3-α Compounded with NaCl-KCl as a Composite Electrolyte for Intermediate Temperature Fuel Cell.
SrCeO₃ and SrCe0.9Sm0.1O3-α were synthesized using a high-temperature solid-state reaction method using Sm₂O₃, SrCO₃, CeO₂ as precursors, then the SrCe0.9Sm0.1O3-α-NaCl-KCl composite electrolyte was fabricated by compounding SrCe0.9Sm0.1O3-α with NaCl-KCl and sintering it at a lower temperature (750 °C) than that of a single SrCeO₃ material (1540 °C). The phase and microstructure of the samples were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The conductivities of the samples were measured in dry nitrogen atmosphere using electrochemical analyzer. The conductivities of the SrCeO₃, SrCe0.9Sm0.1O3-α and SrCe0.9Sm0.1O3-α-NaCl-KCl at 700 °C were 2.09 × 10-5 S·cm-1, 1.82 × 10-3 S·cm-1 and 1.43 × 10-1 S·cm-1 respectively. The conductivities of SrCe0.9Sm0.1O3-α-NaCl-KCl composite electrolyte are four orders of magnitude higher than those of SrCeO₃ and two orders of magnitude higher than those of SrCe0.9Sm0.1O3-α. The result of logσ ~ logpO₂ plot indicates that SrCe0.9Sm0.1O3-α-NaCl-KCl is almost a pure ionic conductor. The electrolyte resistance and the polarization resistance of the H₂/O₂ fuel cell based on SrCe0.9Sm0.1O3-α-NaCl-KCl composite electrolyte under open-circuit condition were 1.0 Ω·cm² and 0.2 Ω·cm² respectively. Further, the obtained maximum power density at 700 °C was 182 mW·cm-2.


The His-tag as a decoy modulating preferred orientation in cryoEM.
The His-tag is a widely used affinity tag that facilitates purification by means of affinity chromatography of recombinant proteins for functional and structural studies. We show here that His-tag presence affects how coproheme decarboxylase interacts with the air-water interface during grid preparation for cryoEM. Depending on His-tag presence or absence, we observe significant changes in patterns of preferred orientation. Our analysis of particle orientations suggests that His-tag presence can mask the hydrophobic and hydrophilic patches on a protein's surface that mediate the interactions with the air-water interface, while the hydrophobic linker between a His-tag and the coding sequence of the protein may enhance other interactions with the air-water interface. Our observations suggest that tagging, including rational design of the linkers between an affinity tag and a protein of interest, offer a promising approach to modulating interactions with the air-water interface.


[Serum levels of antioxidants and vitamins related to the homocystein's metabolism during postmenopause].
To describe nutritional status, B6, B12, and antioxidant vitamins, as well as homocysteine concentrations in postmenopausal women. A cross-sectional study was conducted in Mexico City. One hundred twenty-five women were selected if they were healthy and were in their first five years after menopause onset. Women were spontaneously divided in two groups: women who did not receive any hormonal treatment for at least six months before the study (n = 66), and those who received hormonal treatment at the moment of the study (n = 59). Anthropometry was measured and a fasting blood sample from a peripheral vein was obtained to determine homocysteine, vitamins A, C, E, B6, B12, and folic acid. Results were compared with Student t-test, and a logistic regression model was used to calculate the risk of hyperhomocystinemia after adjusting by some potential confounders. Women who did not receive hormone replacement therapy presented higher body mass index and waist-hip ratio than those who received such treatment. In contrast, this group presented higher prevalence of folic acid deficiency and hyperhomocystinemia, despite they consumed higher amounts of folic acid in the diet. This high risk of hyperhomocystinemia was independent of vitamin serum concentrations and the level of physical activity (OR = 15.1, IC95 = 1.60,141.9). These results suggest that hormone replacement therapy may protect against overweight and central fat distribution that occur after menopause, but increases the risk of hyperhomocystinemia.


Use of N-benzoyl-L-tyrosine thiobenzyl ester as a protease substrate. Hydrolysis by alpha-chymotrypsin and subtilisin BPN.
In the course of searching for specific chromogenic substrates which might be useful in screening for protease-deficient mutants of Bacillus subtilis, we have developed a method for the synthesis of N-benzoyl-L-tyrosine thiobenzyl ester (BzTyrSBzl) in good yield. Spontaneous base hydrolysis of this thiol ester is low, but several serine proteases hydrolyze it readily. Spectrophotometric measurement of the hydrolysis of the ester in the presence of 5,5'-dithiobis(2-nitrobenzoic acid) provides a continuous assay for chymotrypsin as sensitive as any assay reported in the literature. Serine proteases which hydrolyze this substrate may be detected in polyacrylamide disc gels by incubation in the presence of nitro blue tetrazolium. Apparent Km values of 0.02 and 7 mM and kcat values of 37 S-1 and 126 S-1 were observed for the hydrolysis of BzTyrSBzl by alpha-chymotrypsin and subtilisin BPN', respectively. Additionally, 5 mM indole was observed to behave as a strict competitive inhibitor of the alpha-chymotrypsin-catalyzed hydrolysis of BzTyrSBzl but was observed to increase the maximal rate of hydrolysis of p-nitrophenyl acetate by alpha-chymotrypsin by 30%, as previously described. These data, the published data of other workers, and results from studies with molecular models of trypsin and subtilisin BPN' are used as the basis for describing more fully a secondary hydrophobic binding pocket on alpha-chymotrypsin. The pocket is immediately adjacent to the active site serine and is tentatively suggested to be composed of 4 aliphatic side chain residues and 2 glycine residues.


A novel spinal neuron connection for heat sensation.
Heat perception enables acute avoidance responses to prevent tissue damage and maintain body thermal homeostasis. Unlike other modalities, how heat signals are processed in the spinal cord remains unclear. By single-cell gene profiling, we identified ErbB4, a transmembrane tyrosine kinase, as a novel marker of heat-sensitive spinal neurons in mice. Ablating spinal ErbB4+ neurons attenuates heat sensation. These neurons receive monosynaptic inputs from TRPV1+ nociceptors and form excitatory synapses onto target neurons. Activation of ErbB4+ neurons enhances the heat response, while inhibition reduces the heat response. We showed that heat sensation is regulated by NRG1, an activator of ErbB4, and it involves dynamic activity of the tyrosine kinase that promotes glutamatergic transmission. Evidence indicates that the NRG1-ErbB4 signaling is also engaged in hypersensitivity of pathological pain. Together, these results identify a spinal neuron connection consisting of ErbB4+ neurons for heat sensation and reveal a regulatory mechanism by the NRG1-ErbB4 signaling.


Preoperative predicting invasiveness of lung adenocarcinoma manifesting as ground-glass nodules based on multimodal images of dual-layer spectral detector CT radiomics models.
To construct and validate conventional and radiomics models based on dual-layer spectral CT radiomics for preoperative prediction of lung ground glass nodules (GGNs) invasiveness. A retrospective study was conducted on 176 GGNs patients who underwent chest non-contrast enhancement scan on dual-layer spectral detector CT at our hospital within 2 weeks before surgery. Patients were randomized into the training cohort and testing cohort. Clinical features, imaging features and spectral quantitative parameters were collected to establish a conventional model. Radiomics models were established by extracting 1781 radiomics features form regions of interest of each spectral image [120 kVp poly energetic images (PI), 60 keV images and electron density maps], respectively. After selecting the optimal radiomic features and integrating multiple machine learning models, the conventional model, PI model, 60 keV model, electron density (ED) model and combined model based on multimodal spectral images were finally established. The performance of these models was assessed through the evaluation of discrimination, calibration, and clinical application. In the conventional model, age, vacuole sign, 60 keV and ED were independent risk factors of invasiveness. The combined model using logistic regression-least absolute shrinkage and selection operator classifiers was the optimal model with a higher area under the curve of the training (0.961, 95% confidence interval, CI: 0.932-0.991) and testing set (0.944, 0.890-0.999). The combined models are helpful to predict the invasiveness of GGNs before surgery and guide the individualized treatment of patients.


Localization of vascular endothelial growth factor in synovial membrane mast cells: examination with "multi-labelling subtraction immunostaining".
Mast cells are believed to play a novel part in the development of destructive synovial pannus in rheumatoid arthritis (RA). This study was undertaken to investigate the localization of vascular endothelial growth factor (VEGF) in the synovial membrane using a unique immunostaining technique. Synovial specimens of RA patients were examined immunohistochemically and were compared with specimens from non-RA controls. Multi-labelling subtraction immunostaining, a modification of double- and triple-labelling immunostaining, revealed that the VEGF-positive cells were identical to tryptase-positive cells (mast cells). No other cell types were found to be positive for VEGF. The synovium of RA patients showed a larger number of VEGF-positive mast cells than that of non-RA controls (P<0.001). The study suggests that mast cell-derived VEGF may contribute to the development of synovial pannus in RA.


Do marginal changes in PHI membership accurately predict marginal changes in PHI use in Western Australia?
Annual trends in the rate of utilisation of PHI in three different clinical categories were compared with published trends in PHI membership to assess the degree to which PHI membership predicts PHI use in Western Australia. The WA Data Linkage System was used to extract all hospital morbidity records in Western Australia from 1981 to 2001. The adjusted annual incidence rate ratio of hospitalisation as a privately insured patient versus a public (Medicare) patient was estimated using Poisson regression in each clinical category across three age groups in each year. The rate ratios were graphed as segmented trend lines and compared with published data for trends in PHI membership. The most significant changes in the use of PHI versus the public system occurred between 1981 and 1984 overall clinical categories. These changes were consistent with those documented for PHI membership. From 1992 onwards, significant changes in the trend were observed in the surgical clinical category, compared with the medical and obstetric clinical categories. Further, the trend observed in the surgical clinical category at this time was inconsistent with that documented for PHI membership. Between 2000 and 2001, only the surgical clinical category showed a similar change in trend as that documented for PHI membership. Between 1981 and 1991 the timing and direction of changes in PHI membership were found to be congruent with that of PHI use in all three clinical categories. However, between 2000 and 2001 trends in PHI membership were only congruent with trends in PHI use in the surgical clinical category. We conclude that investigating marginal changes in PHI membership represents an incomplete method for assessing the effectiveness of policies aimed at reducing the pressure on the public system.


Effects of simulated herbivory on tillering and reproduction in an annual ryegrass,Lolium remotum.
This study examined the overall impact of simulated herbivory on tillering and reproductive performance of an annual ryegrass,Lolium remotum. The interaction between herbivore damage and intraspecific competition and the effect of the timing of damage were also studied. The experimental plants were sown at two densities and were randomly assigned to eight different damage treatments consisting of artificial leaf area removal by clipping with scissors or removal of one-third of the ripening seeds. The treatments were executed at two flowering stages. The pattern of tiller development differed significantly among treatments and between densities. At the lower density, earlier treatments delayed tiller development more than the same treatments executed later. At the higher density, all treatments delayed tiller development. The density effect was significant for all reproductive traits measured. The reproductive output of plants grown at the higher density was lower and the negative treatment effects were stronger than at the lower density. The treatment effect was significant for seed dry weight per plant and individual seed weight but not for number of seeds per plant. There were no statistically significant interaction effects between the damage treatments and density, suggesting that the plants responded to the damage similarly, irrespective of the density. The plants did not totally compensate for losses due to damage at either density, even though they slightly increased their resource allocation to sexual reproduction at the higher density.


Hydroxychloroquine can potentially interfere with immune function in COVID-19 patients: Mechanisms and insights.
The recent global pandemic due to COVID-19 is caused by a type of coronavirus, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite rigorous efforts worldwide to control the spread and human to human transmission of this virus, incidence and death due to COVID-19 continue to rise. Several drugs have been tested for treatment of COVID-19, including hydroxychloroquine. While a number of studies have shown that hydroxychloroquine can prolong QT interval, potentially increasing risk of ventricular arrhythmias and Torsade de Pointes, its effects on immune cell function have not been extensively examined. In the current review, an overview of coronaviruses, viral entry and pathogenicity, immunity upon coronavirus infection, and current therapy options for COVID-19 are briefly discussed. Further based on preclinical studies, we provide evidences that i) hydroxychloroquine impairs autophagy, which leads to accumulation of damaged/oxidized cytoplasmic constituents and interferes with cellular homeostasis, ii) this impaired autophagy in part reduces antigen processing and presentation to immune cells and iii) inhibition of endosome-lysosome system acidification by hydroxychloroquine not only impairs the phagocytosis process, but also potentially alters pulmonary surfactant in the lungs. Therefore, it is likely that hydroxychloroquine treatment may in fact impair host immunity in response to SARS-CoV-2, especially in elderly patients or those with co-morbidities. Further, this review provides a rationale for developing and selecting antiviral drugs and includes a brief review of traditional strategies combined with new drugs to combat COVID-19.


The impact of pediatric brachial plexus injury on families.
To determine the impact of brachial plexus injuries on families to best meet their clinical and social needs. Our cross-sectional study included families with children between the ages of 1 and 18 years with birth or non-neonatal brachial plexus injuries (BPIs). The consenting parent or guardian completed a demographic questionnaire and the validated Impact on Family Scale during a single assessment. Total scores can range from 0 to 100, with the higher the score indicating a higher impact on the family. Factor analysis and item-total correlations were used to examine structure, individual items, and dimensions of family impact. A total of 102 caregivers participated. Overall, families perceived various dimensions of impact on having a child with a BPI. Total family impact was 43. The 2 individual items correlating most strongly with the overall total score were from the financial dimension of the Impact on Family Scale. The strongest demographic relationship was traveling nationally for care and treatment of the BPI. Severity of injury was marginally correlated with impact on the family. Parent-child agreement about the severity of the illness was relatively high. Caretakers of children with a BPI perceived impact on their families in the form of personal strain, family/social factors, financial stress, and mastery. A multidisciplinary clinical care team should address the various realms of impact on family throughout the course of treatment. Prognostic II.


Extracellular vesicles derived from hypoxic HTR-8/SVneo trophoblast inhibit endothelial cell functions through the miR-150-3p /CHPF pathway.
Endothelial dysfunction is one of the basic pathological changes in pre-eclampsia. Extracellular vesicles (EVs) can transport miRNAs expressed by placental trophoblast cells into endothelial cells. The aim of this study was to explore the differential effects of EVs induced by hypoxic trophoblasts (1%HTR-8-EV) and those derived from normoxic trophoblasts (20%HTR-8-EV) on the regulation of endothelial cell functions. Normoxia and hypoxia were preconditioned to induce trophoblast cells-derived EVs. The effect of EVs, miRNA, target gene, and their interactions on endothelial cell proliferation, migration, and angiogenesis were determined. Quantitative analysis of miR-150-3p and CHPF were verified by qRT-PCR and western blotting. The binding relationship among EVs pathway was demonstrated by luciferase reporter assay. Compared with 20%HTR-8-EV, 1%HTR-8-EV had a suppressive effect on proliferation, migration, and angiogenesis of endothelial cells. The results of miRNA sequencing showed the vital role of miR-150-3p in trophoblast-to-endothelium communication. 1%HTR-8-EV carrying miR-150-3p could move into endothelial cells and target chondroitin polymerizing factor (CHPF) gene. MiR-150-3p inhibited endothelial cell functions by regulating CHPF. In patient-derived placental vascular tissues, there was a similar negative correlating between miR-150-3p and CHPF. Our findings indicate that extracellular vesicles miR-150-3p derived from hypoxic trophoblasts inhibits endothelial cells proliferation, migration, and angiogenesis by modulating CHPF, illuminating a novel mechanism of hypoxic trophoblasts regulation of endothelial cells and their potential role in PE pathogenesis.


Production of reactive oxygen intermediates following CD40 ligation correlates with c-Jun N-terminal kinase activation and IL-6 secretion in murine B lymphocytes.
Recent studies indicate that reactive oxygen intermediates (ROI) serve as second messengers in cell signaling. ROI have been implicated in the activation of NF-kappaB as well as c-Jun N-terminal kinase (JNK) in response to IL-1 and TNF-alpha stimulation. In this report we examine whether intracellular ROI are involved in CD40 receptor signaling. We show that CD40 engagement on resting splenic B lymphocytes and murine B lymphoma WEHI 231 cells generates ROI. Blocking ROI production by preincubation with the antioxidant N-acetyl-L-cysteine inhibits JNK activation, NF-kappaB-driven luciferase activity, and IL-6 secretion following CD40 ligation, suggesting a role for ROI in CD40-mediated signaling events. Furthermore, transfection of WEHI 231 cells with a plasmid encoding Mn-superoxide dismutase interferes with CD40-induced NF-kappaB activation, providing further support for ROI involvement in this pathway. Collectively, these data demonstrate that ROI may serve as second messengers linking CD40 engagement on B cells to important downstream activation events.


Prospective case series of neuropathic cancer pain in patients treated with an EGFR-inhibitor.
Novel treatments of neuropathic pain are urgently needed. Rapid relief of neuropathic cancer pain in patients treated with epidermal growth factor receptor (EGFR) inhibitors have been reported. Experiments in rodent models confirm the pain relief and reveal novel mechanisms critically involving the EGFR. Clinical pain research is complicated and patients with advanced cancer are heterogeneous, often with complex, deteriorating clinical pictures, hampering feasibility of drug-trial procedures. Prospective case series exploring the EGFR inhibition/neuropathic cancer pain association in order to inform planning clinical trials. Symptom assessment method was tailored to what was ethical, feasible, and clinically relevant for each patient. Patients with neuropathic cancer pain treated off-label with the monoclonal antibody panitumumab were studied to assess feasibility of different measurement tools. Fourteen of 20 patients (70%) experienced clinically significant pain relief. There was good concordance in patient and physician-reported outcomes. Results support panitumumab's potential to be of significant benefit to patients with refractory neuropathic cancer pain. Findings also reinforce the difficulty of using conventional drug trial endpoints and designs in this population. Innovative research methods must be considered for much needed pivotal trials.