Hip involvement in ankylosing spondylitis.
Hip involvement in ankylosing spondylitis (AS) is a common and disabling problem. The clinical and x-ray records of 87 patients with definite AS (Rome criteria) were examined to define and characterize their hip disease. Clinical hip disease was present in 33 cases (38%), was usually bilateral (91%), and tended to begin early in the disease course; it was the cause of 50% of the Class III and IV disability in the entire study group. Typical findings included regional pain, limitation of motion, muscle atrophy, and flexion contractures. Radiologic hip abnormalities occurred in 42 cases (48%). The radiographic pattern was distinctive when compared to that in two control groups and included axial migration of the femoral head (63%), concentric joint space narrowing (50%), rufflike femoral osteophytosis (36%), and protrusio acetabuli (30%). Eight patients required bilateral hip surgery. Para-articular ossification occurred in 8 of 16 replaced hips; in 5 of 8 hips it caused clinical immobility. This potentially serious complication may limit the usefulness of hip arthroplasty in some AS patients.


[Surgical treatment of hydatid cysts].
Hydatidosis represents a form of helminthic zoonosis with a stronger medical, social and economic impact. It is endemic in some areas of the world including Mediterranean countries, and therefore Italy. The disease is often diagnosed in an advanced phase, due to the poor symptomatology in the early stages. The best treatment is surgery. Emergency surgery is similar to elective surgery, though in some cases is preferable only a drainage procedure until the stabilization of the genreal and local conditions of the patient allow a radical intervention. The Authors report on their five year experience of surgical treatment of compliated pulmonar hydatidosis pointing out that exeresis must be aimed at preserving pulmonar function as much as possible.


Thermally stimulated luminescence glow curve structure of β-irradiated CaB4O7:Dy.
Thermally stimulated luminescence glow curves of CaB4O7:Dy samples after β-irradiation showed glow peaks at ~335, 530 and 675 K, with a heating rate of 2 K/s. The main peak at 530 K was analyzed using the Tmax-Tstop method and was found to be composed of at least five overlapping glow peaks. A curve-fitting program was used to perform computerized glow curve deconvolution (CGCD) analysis of the complex peak of the dosimetric material of interest. The kinetic parameters, namely activation energy (E) and frequency factor (s), associated with the main glow peak of CaB4O7:Dy at 520 K were evaluated using peak shape (PS) and isothermal luminescence decay (ILD) methods. In addition, the kinetics was determined to be first order (b =1) by applying the additive dose method. The activation energies and frequency factors obtained using PS and ILD methods are calculated to be 0.72 and 0.72 eV and 8.76 × 10(5) and 1.44 × 10(6) /s, respectively.


Coupling of muscle phosphorylation potential to glycolysis during work after short-term training.
To examine whether the metabolic adaptations to short-term training are expressed over a range of submaximal levels of mitochondrial respiration, seven untrained male subjects [maximal O2 uptake (VO2max) = 45.9 +/- 1.9 (SE) ml.kg-1.min-1] performed a progressive three-stage protocol of cycle exercise at 60% (20 min), 79% (20 min), and 92% (11 min) of pretraining VO2max before and after training. Training consisted of 5-6 days of cycling for 2 h/day at 65% VO2max. Muscle tissue rapidly obtained from the vastus lateralis by needle biopsy indicated that training blunted (P < 0.05) the increase in lactate observed at 60% (23.4 +/- 6.5 vs. 12.4 +/- 2.9 mmol/kg dry wt), 79% (48.9 +/- 5.1 vs. 25.6 +/- 5.2 mmol/kg dry wt), and 92% (68.3 +/- 6.4 vs. 41.5 +/- 6.5 mmol/kg dry wt) of VO2max. Training also resulted in a higher phosphocreatine and lower creatine and P(i) concentrations at both 79% (P < 0.05) and 92% (P < 0.05) of VO2max and higher muscle glycogen levels (P < 0.05). These changes were accompanied by small but significant reductions (P < 0.05) in O2 uptake at the two higher exercise intensities. Given that the lactate-to-pyruvate ratio and the calculated free ADP and AMP were also reduced (P < 0.05), it would appear that short-term training results in a tighter metabolic control over a range of mitochondrial respiratory rates.


Nuclear nonhistone proteins in mouse teratocarcinomas : I. Cell lineage specificity.
The nonhistone protein pattern of four murine teratocarcinomas with different capacities for differentiation were compared: a multidifferentiated teratocarcinoma OTT2289, a nondifferentiated teratocarcinoma OTT2158, a teratocarcinoma-derived rhabdomyosarcoma TDR114, and a teratocarcinoma-derived neuroblastoma TDN2151. Their nonhistone proteins (NHP) were separated by differential salt extraction and hydroxyapatite chromatography into three fractions, NHP-I, NHP-II and NHP-III. Comparison of the NHP fractions by twodimensional gel electrophoresis in combination with a sensitive silver staining method reveals that there are several tumour line specific proteins in each NHP fraction. We suggest that specific NHP, which can be used as biochemical markers for each of the four investigated tumour lines, may be involved in cell lineage specific control of gene expression.


The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy.
With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab), and multikinase inhibitors (sunitinib). The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV) ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.


Pandemic Influenza Readiness Report on Laboratory and Epidemiology Capacity-United States and Territories, 2015.
Laboratory and epidemiologic data are vital to identify a novel influenza A virus and inform the public health response, whether it be to a localized outbreak or pandemic. The Centers for Disease Control and Prevention (CDC) developed the Pandemic Influenza Readiness Assessment (PIRA) to evaluate the state of the nation's preparedness for the next influenza pandemic. Representatives from all 62 Public Health Emergency Preparedness (PHEP) awardee jurisdictions were requested to complete the web-based questionnaire in July 2015. The PIRA consists of 7 modules covering key components of pandemic preparedness; this article summarizes results from the laboratory and epidemiology modules. Many of the jurisdictions reported they had the capacity to fulfill most of the laboratory and epidemiology tasks, including the ability to differentiate novel influenza A viruses from seasonal influenza viruses and electronically transfer laboratory, surveillance, and case investigation data. Pandemic preparedness includes transfer of electronic death records and conducting surveillance for influenza-associated mortality in adults. Although most jurisdictions self-reported that they had the epidemiologic and laboratory capabilities that were assessed, additional planning and technical assistance are needed to ensure all states and territories have and maintain all critical capacities. The results from this PIRA can inform how CDC and federal partners focus future training and outreach.


Bonding, Thermodynamics, and Dissociation Dynamics of NiO+ and NiS+ Determined by Photofragment Imaging and Theory.
We use photofragment ion imaging and ab initio calculations to determine the bond strength and photodissociation dynamics of the nickel oxide (NiO+) and nickel sulfide (NiS+) cations. NiO+ photodissociates broadly from 20350 to 32000 cm-1, forming ground state products Ni+(2D) + O(3P) below ∼29000 cm-1. Above this energy, Ni+(4F) + O(3P) products become accessible and dominate over the ground state channel. In certain images, product spin-orbit levels are resolved, and spin-orbit propensities are determined. Image anisotropy and the results of MRCI calculations suggest NiO+ photodissociates via a 3 4Σ- ← X 4Σ- transition above the Ni+(4F) threshold and via 3 4Σ-, 2 4Σ-, and/or 2 4Π and 3 4Π excited states below the 4F threshold. The photodissociation spectrum of NiS+ from 19900 to 23200 cm-1 is highly structured, with ∼12 distinct vibronic peaks, each containing underlying substructure. Above 21600 cm-1, the Ni+(2D5/2) + S(3P) and Ni+(2D3/2) + S(3P) product spin-orbit channels compete, with a branching ratio of ∼2:1. At lower energy, Ni+(2D5/2) is formed exclusively, and S(3P2) and S(3P1) spin-orbit channels are resolved. MRCI calculations predict the ground state of NiS+ to be one of two nearly degenerate states, the 1 4Σ- and 1 4Δ. Based on images and spectra, the ground state of NiS+ is assigned as 4Δ7/2, with the 1 4Σ3/2- and 1 4Σ1/2- states 81 ± 30 and 166 ± 50 cm-1 higher in energy, respectively. The majority of the photodissociation spectrum is assigned to transitions from the 1 4Δ state to two overlapping, predissociative excited 4Δ states. Our D0 measurements for NiO+ (D0 = 244.6 ± 2.4 kJ/mol) and NiS+ (D0 = 240.3 ± 1.4 kJ/mol) are more precise and closer to each other than previously reported values. Finally, using a recent measurement of D0(NiS), we derive a more precise value for IE (NiS): 8.80 ± 0.02 eV (849 ± 1.7 kJ/mol).


The influence of gentle interactions with an experimenter during milking on dairy cows' avoidance distance and milk yield, flow and composition.
Cattle's relationship with humans is a crucial factor regarding their welfare. In dairy cows, interactions with humans occur regularly during milking. We tested the effect of gentle interactions (stroking, talking in a gentle voice) during milking on avoidance distance and milk composition, yield and flow characteristics as well as behaviour during milking. Over the course of 15 days, an experimenter interacted gently with 14 German Holstein cows for 2 min during morning and evening milkings, totalling 60 min; the experimenter stayed at a similar distance to 12 control cows of the same breed for the same amount of time. There were no significant differences between the groups in behaviour during milking. Over the course of the experimental phase, avoidance distance at the feeding rack decreased significantly in stroked but not in control cows. The treatment did not improve any of the measures of milk composition, yield or flow; on the 1st day of the treatment, milk ejection was impaired in stroked cows, which points towards an effect of the novelty of the treatment. We conclude that gentle interactions during milking improve the relationship between cows and a human. Possible reasons for the absence of an effect on milk characteristics are that cows may not have perceived the interactions as positive or that a ceiling effect occurred due to otherwise optimal milking routines.


[Studies of the fifth section in the introduction of the Qian jin yao fang - Writings quoted from the Shen nong ben cao jing and the Yao dui].
The fifth section in the introduction of the Qian jin yao fang is composed of three paragraphs. The first paragraph is the same as that of the Shen nong ben cao jing. The second and the third ones begin with the sentences of "Lei gong say ..." and "Yao dui says ..." respectively. We inquired into the origin of these three paragraphs. As a result of our investigation, we inferred that the first and the second paragraphs were part of the writings of the Lei gong ji zhu shen nong ben cao and that the third one was part of the Lei gong yao dui. We also pointed out that the substance of these paragraphs was influenced directly and indirectly by Buddhist medicine.


[Polyethylene terephthalate (PET)--health aspects and food packaging application].
Polyethylene terephthalate (PET) due to its physicochemical properties, especially regidity and glass-like transparency is widely used as food packaging material. The relevant legislation states that substances may not migrate from food contacting materials in quantities that may cause undesirable changes in organoleptic properties of food coming into contact with such material. The lists of substances authorized for food contact plastic materials and requirements for the final product were established. The requirements concern global migration limits (60 mg/kg or 10 mg/dm2) and specific migration limits (SML) set for substances which, when migrate into food in grater quantities may cause risk for human health. For the products manufactured from PET the specific migration limits were set for terephthalic acid (7.5 mg/kg), for isophthalic acid (5 mg/kg), for isophthalic acid dimethyl ester (0.05 mg/kg) and for ethylene and diethylene glycol (30 mg/kg). PET may undergo thermal degradation resulting in formation of acetaldehyde, which may influence organoleptic characteristics of packaged foods changing taste and smell.


Tracking changes in composition and amount of dissolved organic matter throughout drinking water treatment plants by comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry.
Dissolved organic matter (DOM) can affect the performance of water treatment processes and produce undesirable disinfection by-products during disinfection. Several studies have been undertaken on the structural characterization of DOM, but its fate during drinking water treatment processes is still not fully understood. In this work, the nontargeted screening method of comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry (GC×GC-qMS) was used to reveal the detailed changes of different chemical classes of compounds in DOM during conventional and advanced drinking water treatment processes at three drinking water treatment plants in China. The results showed that when the dissolved organic carbon removal was low, shifts in the DOM composition could not be detected with the specific ultraviolet absorbance at 254nm, but the changes were clear in the three-dimensional fluorescence excitation-emission matrix or GC×GC-qMS analyses. Coagulation-sedimentation processes selectively removed 37-59% of the nitrogenous compounds, alcohols and aromatic hydrocarbons but increased the concentrations of halogen-containing compounds by 17-26% because of the contact time with chlorine in this step. Filtration was less efficient at removing DOM but preferentially removed 21-60% of the acids. However, other organic matter would be released from the filter (e.g., nitrogenous compounds, acids, and aromatic hydrocarbons). Biological activated carbon (BAC) treatment removed most of the compounds produced from ozonation, particularly ketones, alcohols, halogen-containing compounds and acids. However, it should be noted that certain highly polar or high molecular weight compounds not identified in this study might be released from the BAC bed. After the whole treatment processes, the concentrations of nitrogenous compounds, alcohols, alkenes, aromatic hydrocarbons and ketones were decreased more by the advanced treatment processes than by the conventional treatment processes. Alcohol and ketone removals were probably related to the reduction in protein-like materials. Alkane removal was probably related to the reduction in fulvic acid-like and humic acid-like materials.


The overexpression of long intergenic ncRNA00162 induced by RelA/p65 promotes growth of pancreatic ductal adenocarcinoma.
Recent observations have emphasized the role of long non-coding RNA (lncRNA) in cancer progression; however, a genetic profile of lncRNAs in pancreatic ductal adenocarcinoma (PDAC) remains an ongoing study. In this research, RNA sequencing showed that LINC00162 is dramatically increased in patient-derived tumour cell lines (PATC) compared with the human pancreatic nestin-positive epithelial (HPNE) cells. These data were validated in several PDAC cell lines, and significant upregulation of LINC00162 was found in all of them. Knock-down of LINC00162 significantly inhibited the proliferation, colony formation and migration of PATC cells in vitro and suppressed the growth of PATC xenografts in vivo. Overexpression of LINC00162 in PDAC cell lines (AsPc-1) showed consistent results, with significantly increased proliferation, colony formation and migration of AsPc-1 cells, as well as enhanced tumour growth of the AsPc-1 xenografts in vivo. Furthermore, the result of Chromatin immunoprecipitation assay revealed that RelA/p65 directly bound to LINC00162, and the expression of LINC00162 in PDAC decreased after RelA/p65 knock-down, the proliferation ability of AsPc-1 also significantly inhibited after knocking down LINC00162 and RelA/p65 simultaneously, indicating that RelA/p65 directly involve in the transcriptional regulation of LINC00162. In sum, our results provide first evidence for the role of LINC00162 in promoting PDAC progression and the potential underlying mechanism of LINC00162 overexpression.


MicroRNA 302b-3p/302c-3p/302d-3p inhibits epithelial-mesenchymal transition and promotes apoptosis in human endometrial carcinoma cells.
Studies have shown that the microRNA miR-302 can affect the proliferation, migration and cell cycle progression of endometrial carcinoma (EC). miR-302 clusters have been shown to play an important role in the proliferation and differentiation of cancer cells and in their tumorigenicity. In this study, we detected the expression of genes through quantitative reverse transcription polymerase chain reaction (qRT-PCR). We detected the expression of proteins through Western blot. The Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-staining assay were used to detect the ability of miR-302b-3p/302c-3p/302d-3p to affect the cell apoptosis. The CCK-8 were used to detect the ability of miR-302b-3p/302c-3p/302d-3p to affect the cell proliferation. The Cell cycle analysis were used to detect the ability of miR-302b-3p/302c-3p/302d-3p to affect the cell cycle. Finally, the wound healing assay was used to detect the ability of miR-302b-3p/302c-3p/302d-3p to impact cell migration. We found that miR-302b-3p/302c-3p/302d-3p of the miR-302 cluster was downregulated in EC, and it altered the epithelial-mesenchymal transition (EMT) process in the EC cell lines Ishikawa and HEC-1A. Western blot and the Annexin V- FITC/PI double-staining assay were used to detect the ability of miR-302b-3p/302c-3p/302d-3p to promote the apoptosis of Ishikawa and HEC-1A cells. In addition, qRT-PCR results showed that overexpression of miR-302b-3p/302c-3p/302d-3p significantly inhibited the expression of ZEB1, suppressed the expression of Bcl-2 and promoted the expression of BAX. The overexpression of miR-302b-3p/302c-3p/302d-3p inhibited the proliferation and migration of Ishikawa and HEC-1A cells. Cell cycle analysis showed that miR-302b-3p/302c-3p/302d-3p arrested cell cycle progression in the G0/G1 phase. All results showed that miR-302b-3p/302c-3p/302d-3p can be used as a tumor suppressor in EC and is expected to be a new target for the treatment of EC.


Endovascular treatment of occluded and stenotic visceral vessels in patients with chronic mesenteric ischemia.
Objective Current evidence in the literature about endovascular treatment (ET) of visceral vessels in patients with chronic mesenterial ischemia (CMI) based on morphological characteristics is limited. The aim of this study was the evaluation of ET in occluded and stenotic visceral vessels. Methods Patients undergoing ET for CMI between November 2000 and November 2012 were included in this retrospective study. Primary measure outcome was the symptom-free survival (SFS). Secondary outcomes were primary (PPR), secondary patency (SPR) rates and technical success rate (TSR). A Cox-regression analysis identified risk factors for the primary and secondary measure outcomes. Results Forty patients were included in the present study (men: 21, mean age: 68). The overall number of vessels with intention-to-treat was 62. Fifty-two visceral arteries (18 occlusions and 34 stenoses) were successfully treated by endovascular means. The overall TSR was 84%. Visceral vessel occlusions and atherosclerotic disease of the superior mesenteric artery (SMA) were identified as independent risk factors for poorer TSR ( p < 0.05). The 12-month SFS was 60%. The overall 12-month PPR and SPR were 71% and 94%, respectively. No significant differences were observed between occluded and stenotic vessels ( p > 0.05) concerning the PPR. On the other hand, the subgroup analysis revealed higher SPR among occluded visceral vessels ( p < 0.001) and coeliac axis lesions ( p < 0.001). Conclusions ET was associated with high incidence of symptoms recurrence despite the satisfying patency rates in both occluded and stenotic vessels. Additionally, visceral vessel occlusion and presence of atherosclerotic lesions in the SMA were associated with poorer TSR.


The potential for remote ischemic conditioning to improve outcomes in heart failure.
Heart failure is the end-stage of a variety of underlying cardiovascular diseases and carries a poor prognosis. The condition is caused by a complex interaction between many pathophysiological processes including ischemia, fibrosis, ventricular remodeling, abnormal neurohumoral balance and inflammation. While traditional pharmacological treatment of heart failure often targets only one pathophysiological mechanism, remote ischemic conditioning induces a multitude of cardioprotective effects. In particular, the anti-ischemic, anti-remodeling and anti-inflammatory properties of remote ischemic conditioning may be of relevance. We propose that remote ischemic conditioning may offer a novel strategy to improve outcomes in heart failure.


Epicardial adipose excision slows the progression of porcine coronary atherosclerosis.
In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model. Ossabaw miniature swine (n=9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3-5 mm width coronary EAT (cEAT) resection was performed over the middle segment of the left anterior descending artery (LAD) 15 mm distal to the left main bifurcation. Pigs recovered for 3 months on atherogenic diet. Intravascular ultrasound (IVUS) was performed in the LAD to quantify atheroma immediately after adipectomy and was repeated after recovery before sacrifice. Coronary wall biopsies were stained immunohistochemically for atherosclerosis markers and cytokines and cEAT was assayed for atherosclerosis-related genes by RT-PCR. Total EAT volume was measured by non-contrast CT before each IVUS. Circumferential plaque length increased (p<0.05) in the proximal and distal LAD segments from baseline until sacrifice whereas plaque length in the middle LAD segment underneath the adipectomy site did not increase. T-cadherin, scavenger receptor A and adiponectin were reduced in the intramural middle LAD. Relative to control pigs without CAD, 11β-hydroxysteroid dehydrogenase (11βHSD-1), CCL19, CCL21, prostaglandin D2 synthase, gp91phox [NADPH oxidase], VEGF, VEGFGR1, and angiotensinogen mRNAs were up-regulated in cEAT. EAT volume increased over 3 months. In pigs used as their own controls, resection of cEAT decreased the progression of CAD, suggesting that cEAT may exacerbate coronary atherosclerosis.


Patterns of cytokine and chemokine expression in peripheral blood of patients with COVID-19 associated with disease severity.
Cytokine dysregulation has been proposed as one of the main culprits for severe COVID-19 and poor prognosis. We examined the parallel presence of lymphopoietic, proinflammatory, Th1, Th2, regulatory cytokines, and chemokines in the serum of 47 patients with mild, moderate, and severe COVID-19 and evaluated the association between cytokine concentrations and disease severity. A multiplex quantitative cytokine analysis ProcartaPlex™ immunoassay was applied, using the LuminexTM 200X detection system (Invitrogen). The concentrations of twelve cytokines: IL-18, IFN-gamma, TNF-alpha; IL-21; IL-1alpha, IL-1beta, IL-6, IL-22; IL-10, IL-1RA; IL-7 and IFN-alpha were consistently elevated in the studied serum samples. All examined chemokines-Eotaxin, GRO-alpha, IL-8, IP-10, MCP-1, MIP-1alpha, MIP-1beta, SDF-1alpha, and RANTES, were detectable in all studied groups, confirming their importance in mediating the adaptive immune response regardless of disease severity. The serum concentrations of six mediators: IL-1beta, IL-6, IL-18, IL-10, IL-8, and IP-10, showed statistically significant differences among the groups with different disease severity. IL-6, IL-1beta, and IL-10 were more significantly elevated in severe cases while milder symptoms were associated with lower levels of IL-8 and IP-10. Overall, the studied chemokines demonstrated an associated production in acute COVID-19 infection. A strong correlation was observed between the Th1 mediators IL-18 and IL-10 and the proinflammatory IL-6 in the severe COVID-19 group. Our results indicated that severe COVID-19 was characterized by a dysregulated cytokine pattern whereby the Th1 immune response is outweighed by the immunoregulatory response, while inhibitory signals cannot balance the hyperinflammatory response.


Mitochondrial biosensors.
Biosensors offer an innovative tool for measuring the dynamics of a wide range of metabolites in living organisms. Biosensors are genetically encoded, and thus can be specifically targeted to specific compartments of organelles by fusion to proteins or targeting sequences. Mitochondria are central to eukaryotic cell metabolism and present a complex structure with multiple compartments. Over the past decade, genetically encoded sensors for molecules involved in energy production, reactive oxygen species and secondary messengers have helped to unravel key aspects of mitochondrial physiology. To date, sensors for ATP, NADH, pH, hydrogen peroxide, superoxide anion, redox state, cAMP, calcium and zinc have been used in the matrix, intermembrane space and in the outer membrane region of mitochondria of animal and plant cells. This review summarizes the different types of sensors employed in mitochondria and their main limits and advantages, and it provides an outlook for the future application of biosensor technology in studying mitochondrial biology.


[Effect of Tripterygium Glycosides Tablets in treating rheumatoid arthritis:a systematic review and Meta-analysis].
To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.


Post-acute sequelae of COVID-19 and the mental health implications.
Post-acute sequelae of COVID-19 (PASC) or more commonly known as Long COVID-19, is the term given to persistent symptoms 12 weeks from the initial presentation of COVID-19 infection. Several multi-organ symptoms have been reported by patients. Some common symptoms include headaches, fatigue, memory impairment and mental health complications such as anxiety and depression. People with previous psychiatric diagnosis are at greater risk of developing longer mental health implications from persistent COVID-19 symptoms. Additionally, healthcare workers are at increased risk of being long haulers leading to burnout and exhaustion. The objective of this review article is to provide comprehensive evidence from existing literature on various symptoms reported by patients experiencing Long COVID-19 and the rate of occurrence of such symptoms in different populations. A long-term disease surveillance is required to further understand the persistent symptoms or the long-term impact of this infection.


Induction of apoptosis in the germ cells of adult male rats after exposure to cyclophosphamide.
Treatment with cyclophosphamide, a commonly used anticancer drug, may result in oligozoospermia or azoospermia. The objective of this study was to determine whether exposure of male rats to cyclophosphamide induces apoptosis in male germ cells, and if so, when the peak of apoptosis occurs and at what specific stages of spermatogenesis. The presence of apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) detection in situ and by an increase in DNA fragmentation (DNA ladder). To determine the time course of drug-induced apoptosis, male Sprague-Dawley rats were treated with a single dose (70 mg/kg BW) of cyclophosphamide, and the testes were fixed 0, 4, 8, 12, 18, 24, and 48 h after treatment. To determine the dose response, rats were treated with doses of cyclophosphamide (0, 2, 7, 20, and 70 mg/kg), and the testes were fixed 12 h after treatment. A low spontaneous incidence of apoptosis was observed in controls, in particular in premeiotic germ cells of stages I-IV and XI-XIV of the seminiferous tubules. In cyclophosphamide-exposed rats, the incidence of apoptosis increased progressively at 4 h and 8 h, reached a peak at 12 h (about 3.5-fold above control), and then decreased rapidly to control levels by 48 h. A 70-mg/kg dose of cyclophosphamide induced a significant increase in apoptosis; lower doses did not. Although drug-induced apoptosis occurred in all stages of germ cells, it was most pronounced in spermatogonia and spermatocytes in stages I-IV and XI-XIV. Thus, apoptosis may be involved in the occurrence of oligozoospermia or azoospermia after cyclophosphamide treatment. Apoptosis of damaged premeiotic germ cells may serve a critical role in protecting subsequent generations from the diverse effects of toxicants.


Nonlinear hyperlens.
The performance of an optical hyperlens made of metal-dielectric layers can be improved by incorporating self-focusing nonlinearity in the dielectric layers. Using a modified beam propagation method in cylindrical coordinates, we show increased bandwidth and better propagation length, which can improve the spatial and temporal resolution of the device.


Novel Osteobiologics and Biomaterials in the Treatment of Spinal Disorders.
Spinal osteobiologics have evolved substantially in this century after the development of many product categories such as growth factors, allograft, and stem cells. The indications for the use of novel biologics within spine surgery are rapidly expanding as the mechanism of each is elucidated. While the knowledge base of bone morphogenetic protein increases with each subsequent year, the application of new nanotechnology and cell-based strategies are being reported. This review will discuss the most recent data in novel osteobiologics, and where we could use future study.


Ab initio determination of the electron affinities of DNA and RNA nucleobases.
High-level quantum-chemical ab initio coupled-cluster and multiconfigurational perturbation methods have been used to compute the vertical and adiabatic electron affinities of the five canonical DNA and RNA nucleobases: uracil, thymine, cytosine, adenine, and guanine. The present results aim for the accurate determination of the intrinsic electron acceptor properties of the isolated nucleic acid bases as described by their electron affinities, establishing an overall set of theoretical reference values at a level not reported before and helping to rule out less reliable theoretical and experimental data and to calibrate theoretical strategies.


Circular enamel hypoplasia: a rare enamel developmental disturbance in permanent teeth.
Circular enamel hypoplasia, a type of enamel hypoplasia is an extensive enamel disturbance that results in a demarcating line surrounding the crown of the injured teeth visible both clinically and radiographically that most frequently occurs as a result of trauma in children around the age of two years. Clinical features include poor aesthetics, dentin sensitivity, increased susceptibility to dental caries and malocclusion. Early radiographic diagnosis of such teeth is important for timely intervention and subsequent treatment.


Combination therapy with catechins and caffeine inhibits fat accumulation in 3T3-L1 cells.
Catechins and caffeine, which are green tea components, have a slimming effect; however, the combinational effect of fat metabolism in 3T3-L1 cells remains unclear. In the present study, 3T3-L1 cells were treated with catechins and caffeine in combination, and it was found that combination therapy with catechins and caffeine markedly reduced intracellular fat accumulation, mRNA expression levels of peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein α in the early stage of cell differentiation were significantly reduced, and mRNA expression of fatty acid synthetase(FAS) andglycerol-3-phosphate dehydrogenase protein expression levels of FAS were downregulated. Noradrenaline-induced lipolysis was enhanced by caffeine, which markedly increased the protein expression of adipose triglyceride lipase and hormone sensitive lipase. These results indicated that combination therapy with catechins and caffeine synergistically inhibited lipid accumulation by regulating the gene and protein expression levels of lipid metabolism-related enzymes. Therefore, catechins and caffeine combination therapy has potential as a functional food that may be used to prevent obesity and lifestyle-associated diseases.


[Celiac disease : Pathogenesis, clinics, epidemiology, diagnostics, therapy].
Celiac disease is induced by the consumption of gluten containing cereals (wheat, spelt, barley, rye). With a prevalence of ~ 1 %, it is the most common non-infectious chronic inflammatory intestinal disease worldwide. It manifests in all age groups, either classically with abdominal pain, diarrhoea and growth failure or weight loss, more commonly with indirect consequences of malabsorption, such as anaemia and osteoporosis, or with associated autoimmune diseases like type 1 diabetes, autoimmune thyroiditis or dermatitis herpetiformis. The pathogenesis of celiac disease is well explored. Gluten, the cereal storage protein, is not completely digested and reaches the intestinal mucosa where it activates inflammatory T cells, which cause atrophy of the resorptive villi. This T‑cell activation requires a genetic predisposition (the molecules HLA-DQ2 or -DQ8 on antigen-presenting immune cells). Moreover, the enzyme tissue transglutaminase (TG2) which is released in the mucosa increases the immunogenicity of the gluten peptides by a deamidation reaction. The test for serum antibodies to the autoantigen TG2 is one of the best diagnostic markers in medicine, which in combination with endoscopically obtained biopsies, secures the diagnosis of celiac disease. Despite these tools celiac disease is severely underdiagnosed, with 80-90 % of those affected being undetected. The untreated condition can lead to grave complications. These include the consequences of malabsorption, cancers (especially intestinal T‑cell lymphoma), and likely also the promotion of autoimmune diseases. The therapy of celiac disease, a strict gluten-free diet, is difficult to maintain and not always effective. Alternative, supporting pharmacological therapies are urgently needed and are currently in development.


Bilateral total knee arthroplasty increases the propensity to trip on an obstacle.
Tripping over an obstacle is the most frequent cause of falls. We examined the effects of total knee arthroplasty on obstacle avoidance success rates in older adults. Obstacle avoidance success rates, body mass index, visual acuity, contrast sensitivity, depth perception, and single-leg stance duration were evaluated in 29 subjects who had bilateral total knee arthroplasties (age range, 72.6 +/- 5.4 years) and 27 age-matched healthy control subjects (age range, 70.6 +/- 5.5 years). The patients who had total knee arthroplasties had a lower obstacle avoidance success rate, lower single-leg stance duration, and greater body mass index than control subjects. Age, contrast sensitivity, and depth perception were not different between patients who had total knee arthroplasties and control subjects. Obstacle avoidance success rates decreased linearly as single-leg stance duration decreased in the control group and across all groups, but not in the group that had total knee arthroplasties. Linear relationships between obstacle avoidance success rates and body mass index existed for all subjects but not for the group that had total knee arthroplasties or the control group individually. Total knee arthroplasty reduces obstacle avoidance success rate, suggesting that persons who have total knee arthroplasties have an increased propensity to trip on an obstacle and fall. Increased body mass index and decreased single-leg stance duration in patients who have total knee arthroplasties are associated with a decreased obstacle avoidance success rate.


Induction of oligodendrocyte differentiation and in vitro myelination by inhibition of rho-associated kinase.
In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin degradation results in loss of axonal function and eventual axonal degeneration. Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to remyelination of denuded axons occurs regularly in early stages of MS but halts as the pathology transitions into progressive MS. Pharmacological potentiation of endogenous OPC maturation and remyelination is now recognized as a promising therapeutic approach for MS. In this study, we analyzed the effects of modulating the Rho-A/Rho-associated kinase (ROCK) signaling pathway, by the use of selective inhibitors of ROCK, on the transformation of OPCs into mature, myelinating oligodendrocytes. Here we demonstrate, with the use of cellular cultures from rodent and human origin, that ROCK inhibition in OPCs results in a significant generation of branches and cell processes in early differentiation stages, followed by accelerated production of myelin protein as an indication of advanced maturation. Furthermore, inhibition of ROCK enhanced myelin formation in cocultures of human OPCs and neurons and remyelination in rat cerebellar tissue explants previously demyelinated with lysolecithin. Our findings indicate that by direct inhibition of this signaling molecule, the OPC differentiation program is activated resulting in morphological and functional cell maturation, myelin formation, and regeneration. Altogether, we show evidence of modulation of the Rho-A/ROCK signaling pathway as a viable target for the induction of remyelination in demyelinating pathologies.


[Applications of minimally invasive bone splitting technique in cases with missing maxillary anterior teeth and obvious labial alveolar bone depression for dental implantation].
The purpose of this study was to introduce a minimally invasive bone splitting technique which is suitable for cases with missing anterior teeth and obvious depression of alveolar bone in labial side, and to evaluate its clinical results. Minimally invasive bone splitting technique was used in 8 healthy adults with bone defects in the aesthetic zone. The labial alveolar bone incisions were confined around the bone defects which were smaller than traditional incisions. The other procedures were the same as conventional bone splitting technique. Cone-beam CT (CBCT) for missing anterior teeth was taken before surgery, after the surgery and 6 months after surgery and alveolar bone height and width were recorded with landmark identification designed by ourselves in this study. The data were analyzed with SPSS 21.0 software package for paired t test. Paired t test indicated that after surgery and six months after surgery, the labial bone defect was significant improved (P<0.05), but the height of the alveolar ridge bone didn't increase significantly (P>0.05) while the width of the alveolar ridge bone significant improved (P>0.05). This minimally invasive technique can achieve good clinical results for not only intact labial alveolar ridge bones but also good bone grafts, which is beneficial to implantation and prosthetic aesthetics. The long-term outcome needs to be observed.


Intense white luminescence from combustion synthesized Ca12Al14O33:Yb(3+)/Yb(2+) single phase phosphor.
The Ca(12)Al(14)O(33):Yb(3+)/Yb(2+) single phase nano-phosphor has been synthesized through combustion route and its luminescence and lifetime studies have been carried out up to 20 K using 976 and 266 nm excitations. The samples heated in open atmosphere have shown the presence of Yb in Yb(3+) and Yb(2+) states. The 976 nm excitation results a cooperative upconversion emission at 486 nm due to the Yb(3+) state and a broad band in the blue region and has been assigned to arise from the defect centers. The 266 nm excitation on the other hand results a broad emission band even from as-synthesized phosphor without doping of Yb, the width of which increases in presence of Yb due to the emission from Yb(2+) ions formed in heated samples. The white emission covers almost whole visible region with bandwidth 190 nm. The ions in Yb(2+) state has been found to increase with the increase in heating temperature up to 1,273 K. A back conversion of Yb(2+) to Yb(3+) has been observed for higher temperatures. Effect of boric and phosphoric acids as flux on the emission properties of Yb(3+) and Yb(2+) states have been examined and discussed. Quantum yield of emission has also been determined for different samples.


Progesterone vaginal ring as a new contraceptive option for lactating mothers: Evidence from a multicenter non-randomized comparative clinical trial in India.
Evaluate and compare contraceptive efficacy, safety, continuation rates and duration of lactational amenorrhea (LA) in married lactating women (20-35 years) using the progesterone vaginal ring (PVR) or Copper-T380A intrauterine device (IUD) during the first postpartum year. We conducted a one-year multicenter, non-randomized, non-inferiority, open-label, comparative trial at 20 centers in India and compared efficacy, safety, continuation and LA plus feeding patterns and growth/well-being of participants' infants. Women used four 3-month PVRs consecutively (lost PVRs were not replaced) and were to breastfeed at least four times/day. We used Pearl Index (PI) and Kaplan Meier (K-M) rates to analyze pregnancy and K-M for continuation. We enrolled 789 women (459 PVR, 330 IUD). Neither PI nor K-M one-year pregnancy rates differed significantly between groups (PI: PVR-0.62; IUD-0.35); (K-M: PVR-0.7; IUD-0.4, p = 0.58). Continuation rates at 12 months were 78.5% (IUD) vs. 56.9% (PVR) (p < 0.001). Ring expulsions and menorrhagia were the most common discontinuation among PVR/IUD users respectively. The median duration of LA among PVR vs. IUD users was 405 vs. 120 days (p < 0.001). Both groups reported similar adverse events (PVR: 24.2%; IUD: 23.0%); there were no serious adverse events among PVR users. Infants from both groups fed 12-7 times/day and grew at expected rates. Efficacy and safety outcomes were comparable among women in both groups. Continuation rates for PVR, a woman-controlled method, were shorter than IUD rates while PVR users maintained LA significantly longer than IUD users. Infant breastfeeding and growth patterns/well-being were favorable in both groups. PVR, a user-controlled device, offers an additional contraceptive choice for lactating women for one-year postpartum use and can help to address the unmet need for contraception among postpartum women while encouraging breastfeeding to enhance infant growth and well-being.


Effects of gravity on ontogeny in animals.
This brief review leads to the following conclusions: (i) Inversion or clinostat rotation of frogs' eggs demonstrated a critical period of enhanced gravity-sensitivity prior to the first cleavage. These results were corroborated by centrifugation studies which localized the period of maximal sensitivity at approximately 20 minutes post-fertilization. (ii) Eggs of various invertebrates suspended in aqueous solution proved capable of normal development following brief ultracentrifugation. (iii) Among fly larvae, grasshopper nymphs, turtles, mice, rats and chickens, growth rates were inversely related to G-force and maximal chronic acceleration tolerated was inversely related to body size. (iv) Body composition data demonstrated the importance of separately evaluating fat and the fat-free portion of the body in studies of the effect of acceleration on growth in homeotherms. (v) The attempt to evaluate the effect of weightlessness on development of frogs' eggs in Biosatellite 2 was inconclusive for technical reasons.


Coping strategies and patterns of alcohol and drug use among HIV-infected patients in the United States Southeast.
Alcohol and drug use are common among HIV-infected patients and are important determinants of secondary transmission risk and medication adherence. As part of the Coping with HIV/AIDS in the Southeast (CHASE) Study, 611 HIV-infected patients were consecutively recruited from eight clinical care sites in five southeastern U.S. states in 2001-2002. We examined the distribution and predictors of alcohol and drug use in this sample with an emphasis on psychosocial predictors of use. In the prior 9 months, 27% of participants drank alcohol and 7% drank to intoxication at least weekly. The most common drugs used at least weekly were marijuana (12%) and crack (5%); 11% used a non-marijuana drug. 7% reported polysubstance use (use of multiple substances at one time) at least weekly. Injection drug use was rare (2% injected at least once in the past 9 months). There were few differences in alcohol and drug use across sociodemographic characteristics. Stronger adaptive coping strategies were the most consistent predictor of less frequent alcohol and drug use, in particular coping through action and coping through relying on religion. Stronger maladaptive coping strategies predicted greater frequency of drinking to intoxication but not other measures of alcohol and drug use. Those with more lifetime traumatic experiences also reported higher substance use. Interventions that teach adaptive coping strategies may be effective in reducing alcohol and substance use among HIV-positive persons.


Plasma cell granuloma of lung.
A 10 years old girl presented with fever, cough, haemoptysis, dyspnoea on exertion of two months duration. Chest skiagram and CT-scan of thorax revealed well defined mass lesion of varying density occupying right upper and middle lobes with areas of calcification. On thoracotomy, a huge mass in the right upper lobe was resected and hispathological examination proved it to be a case of plasma cell granuloma.


Structural basis of transcriptional activation by the OmpR/PhoB-family response regulator PmrA.
PmrA, an OmpR/PhoB-family response regulator, triggers gene transcription responsible for polymyxin resistance in bacteria by recognizing promoters where the canonical-35 element is replaced by the pmra-box, representing the PmrA recognition sequence. Here, we report a cryo-electron microscopy (cryo-EM) structure of a bacterial PmrA-dependent transcription activation complex (TAC) containing a PmrA dimer, an RNA polymerase σ70 holoenzyme (RNAPH) and the pbgP promoter DNA. Our structure reveals that the RNAPH mainly contacts the PmrA C-terminal DNA-binding domain (DBD) via electrostatic interactions and reorients the DBD three base pairs upstream of the pmra-box, resulting in a dynamic TAC conformation. In vivo assays show that the substitution of the DNA-recognition residue eliminated its transcriptional activity, while variants with altered RNAPH-interacting residues resulted in enhanced transcriptional activity. Our findings suggest that both PmrA recognition-induced DNA distortion and PmrA promoter escape play crucial roles in its transcriptional activation.


Isotopic fractionation of endogenous anabolic androgenic steroids and its relationship to doping control in sports.
The use of gas chromatography (GC)-combustion (C)-isotope ratio mass spectrometry (IRMS) demonstrates that a single oral administration of dehydroepiandrosterone (DHEA, 100 mg) to a male subject significantly lowers the 13C content of etiocholanolone (Et) and androsterone (A) in the subject's urine. The difference in carbon isotope ratio (d13C per thousand) values between Et and A increases from 1.6 per thousand at the time of administration to 5.1 per thousand at 26 h post-administration, indicating preferential metabolism of administered DHEA to form Et in relation to A. Multiple oral administrations of DHEA to a male subject reveals lower d13C values during the excretion period of Et (-31.7 per thousand to -34.6 per thousand) and A (-31.4 per thousand to -33.0 per thousand) to that of the d13C value of the administered DHEA (-31.3 per thousand). Reference distributions of d13C Et and d13C A constructed from normal athlete populations within Australia and New Zealand show a small natural discrimination against 13C in the formation of Et relative to A (mean=0.3 per thousand, n=167, p=0.007). Amplified differences between d13C Et and d13C A, and in vivo 13C depletion measured by GC-C-IRMS are shown to be potentially useful for doping control.


Geometry-Programmable Perovskite Microlaser Patterns for Two-Dimensional Optical Encryption.
Lasing signals with easily distinguishable readout and cavity-geometry-dependent output are emerging as novel cryptographic primitives for two-dimensional (2D) optical encryption, while their practical application is restricted by the challenge of integrating different lasing elements onto an identical 2D pattern. Herein, a lithographic template-confined crystallization approach was proposed to prepare large-scale perovskite microstructures with any desired geometries and locations, which enabled them to serve as 2D lasing patterns for reliable encryption and authentication. These prepatterned perovskite microstructures realized whispering-gallery-mode lasing and also demonstrated outstanding reproducibility of lasing actions. Benefiting from the feature of their cavity-geometry-dependent lasing thresholds, we achieved controllable laser output from different shaped elements, which was further utilized for the proof-of-concept demonstration of a cryptographic implementation. The remarkable lasing performance and feasible preparation of 2D microlaser patterns with customized geometries and locations provide us deep insights into the concepts and fabrication technologies for 2D optical encryption.


[Successful removal of aberrant needles in the pericardium and lung].
A 28-year-old woman who had been diagnosed as schizophrenia was admitted to our hospital, complaining of chest pain. Her chest X-ray demonstrated 9 foreign bodies in the pericardium, lung and others. Her chest computed tomography (CT) confirmed needle-like shadows in the pericardium and lung. They were diagnosed as aberrant needles, and surgically removed. The intrapulmonary aberrant needle was removed with video-assisted thoracoscopic surgery. Aberrant needle in pericardium or lung should be removed surgically, because it is very dangerous. Intraoperative chest X-ray is always necessary before closing the wound to avoid leaving the residual fragments.


Rosai Dorfman syndrome with sinonasal mucosa and intraocular involvement.
A 15 year-old-male presented with concurrent sinonasal polyposis and anterior uveitis with cervical lymph node enlargement. Cervical lymph node biopsy confirmed Rosai-Dorfman disease. Though patient's eye symptoms did not respond well to topical corticosteroid treatment but he showed a remarkable regression in the size of nasal polyps and cervical lymph nodes after systemic corticosteroids. Intraocular involvement in such a case is rare.


Unmasked immune reconstitution inflammatory syndrome towards B-cell non-Hodgkin lymphoma during treatment of esophageal actinomycosis in a patient with advanced HIV: a case report.
Actinomycosis is an unusual chronic bacterial infection, even rarer in people living with HIV. It is not considered an AIDS-defining disease. However, the role in co-presentation or overlap with other opportunistic conditions of advanced HIV is unknown. A 49-year-old Peruvian male presented with a 4-month history of dysphagia, odynophagia, hyporexia and wasting. He underwent an upper digestive endoscopy, in which ulcers with a necrotic center were observed, therefore, the initial diagnostic assumption was esophageal cancer. Subsequent pathology report excluded neoplasms and confirmed the diagnosis of actinomycosis. Serology for human immunodeficiency virus was requested, yielding a positive result. Antimicrobial treatment with amoxicillin and antiretroviral therapy were indicated, with slow clinical improvement. After 4 months, epigastric discomfort presented, for which a new upper digestive endoscopy was performed, revealing a deep gastric ulcer, which was compatible with diffuse large B-cell non-Hodgkin lymphoma. Esophageal actinomycosis in people living with HIV is very rare. We suggest HIV-associated immunosuppression is not enough to allow for actinomycosis to develop, and masked underlying entities should be sought. The existence of such entities in people living with HIV should raise awareness of the possibility of unmasked immune reconstitution inflammatory syndrome once treatment has started.


Pixel-by-pixel deconvolution of bolus-tracking data: optimization and implementation.
Quantification of haemodynamic parameters with a deconvolution analysis of bolus-tracking data is an ill-posed problem which requires regularization. In a previous study, simulated data without structural errors were used to validate two methods for a pixel-by-pixel analysis: standard-form Tikhonov regularization with either the L-curve criterion (LCC) or generalized cross validation (GCV) for selecting the regularization parameter. However, problems of image artefacts were reported when the methods were applied to patient data. The aim of this study was to investigate the nature of these problems in more detail and evaluate strategies of optimization for routine application in the clinic. In addition we investigated to which extent the calculation time of the algorithm can be minimized. In order to ensure that the conclusions are relevant for a larger range of clinical applications, we relied on patient data for evaluation of the algorithms. Simulated data were used to validate the conclusions in a more quantitative manner. We conclude that the reported problems with image quality can be removed by appropriate optimization of either LCC or GCV. In all examples this could be achieved with LCC without significant perturbation of the values in pixels where the regularization parameter was originally selected accurately. GCV could not be optimized for the renal data, and in the CT data only at the cost of image resolution. Using the implementations given, calculation times were sufficiently short for routine application in the clinic.


[Vasculitis in childhood].
1. Vasculitis syndromes in children present with special features. The hypersensitivity vasculitides predominate with Henoch-Schoenlein purpura as a typical representative. Within the polyarteritis-nodosa-group we can distinguish an infantile form with involvement of coronary vessels. This disease resembles Kawasaki's syndrome. 2. The different vasculitis syndromes show a great variety in their clinical presentation; overlapping syndromes are possible. Diagnosis, however, is mostly based on clinical features, supported by laboratory data. In doubtful cases histologic and immunohistologic findings can prove helpful. Their diagnostic value should only be interpreted together with the clinical picture. Since specific findings are often missing we have to exclude all similar diseases. Especially systemic juvenile chronic arthritis, connective tissue diseases, several infections and sometimes malignancies have to be considered. 3. For the future we expect further differentiation and identification of new disease entities, thus hoping for a better classification.


Introducing a nationally shared electronic patient record: case study comparison of Scotland, England, Wales and Northern Ireland.
To compare the experience of the four UK countries in introducing nationally accessible electronic summaries of patients' key medical details, intended for use in emergency and unscheduled care episodes, and generate transferable lessons for other countries. Secondary analysis of data collected previously on all four schemes; cross-case comparison using a framework derived from diffusion of innovations theory. Whilst all four programmes shared a similar vision, they differed widely in their strategy, budget, implementation plan, approach to clinical and public engagement and approach to evaluation and learning. They also differed, for various reasons, in stakeholder alignments, the nature and extent of resistance to the programme and the rate at which records were created. A nationally shared, widely accessible electronic record has powerful symbolic meaning; it may or may not be perceived as improving the quality and safety of care or (alternatively) as threatening patient confidentiality or the traditional role of the doctor or nurse. 'Hard' project management oriented to achieving specific milestones and deadlines sometimes appeared counterproductive when it cut across the 'softer' aspects of the programmes. When designing and implementing complex technologies with pervasive implications, policymakers must consider not only technical issues but also the personal, social and organisational aspects of the programme. A judicious blend of 'hard' and 'soft' management appears key to managing such programmes.


Maternal serum alpha-fetoprotein screening activities of state health agencies: a survey.
Maternal serum alpha-fetoprotein (MSAFP) screening has been demonstrated to be cost-effective on a population basis and is becoming standard practice. The American Society of Human Genetics has twice published policy statements to define the essential elements of a quality screening program. The present study reviewed the impact of these policy statements on state public-health agencies with respect to regulation or provision of MSAFP screening in their jurisdictions. With a few exceptions, states have not elected to play a major role in provision or regulation of this test. There is need to address issues of funding, standards, and data collection in a collaborative effort, if policy statements on genetic services are to be translated into effective state population screening.


Neuroglobin overexpression plays a pivotal role in neuroprotection through mitochondrial raft-like microdomains in neuroblastoma SK-N-BE2 cells.
Since stressing conditions induce a relocalization of endogenous human neuroglobin (NGB) to mitochondria, this research is aimed to evaluate the protective role of NGB overexpression against neurotoxic stimuli, through mitochondrial lipid raft-associated complexes. To this purpose, we built a neuronal model of oxidative stress by the use of human dopaminergic neuroblastoma cells, SK-N-BE2, stably overexpressing NGB by transfection and treated with 1-methyl-4-phenylpyridinium ion (MPP+). We preliminary observed the redistribution of NGB to mitochondria following MPP+ treatment. The analysis of mitochondrial raft-like microdomains revealed that, following MPP+ treatment, NGB translocated to raft fractions (Triton X-100-insoluble), where it interacts with ganglioside GD3. Interestingly, the administration of agents capable of perturbating microdomain before MPP+ treatment, significantly affected viability in SK-N-BE2-NGB cells. The overexpression of NGB was able to abrogate the mitochondrial injuries on complex IV activity or mitochondrial morphology induced by MPP+ administration. The protective action of NGB on mitochondria only takes place if the mitochondrial lipid(s) rafts-like microdomains are intact, indeed NGB fails to protect complex IV activity when purified mitochondria were treated with the lipid rafts disruptor methyl-β-cyclodextrin. Thus, our unique in vitro model of stably transfected cells overexpressing endogenous NGB allowed us to suggest that the role in neuroprotection played by NGB is reliable only through interaction with mitochondrial lipid raft-associated complexes.


Carrier-based strategies for targeting protein and peptide drugs to the lungs.
With greater interest in delivery of protein and peptide-based drugs to the lungs for topical and systemic activity, a range of new devices and formulations are being investigated. While a great deal of recent research has focused on the development of novel devices, attention must now be paid to the formulation of these macromolecular drugs. The emphasis in this review will be on targeting of protein/peptide drugs by inhalation using carriers and ligands.


Pulled, pushed or failed: the demographic impact of a gene drive can change the nature of its spatial spread.
Understanding the temporal spread of gene drive alleles-alleles that bias their own transmission-through modeling is essential before any field experiments. In this paper, we present a deterministic reaction-diffusion model describing the interplay between demographic and allelic dynamics, in a one-dimensional spatial context. We focused on the traveling wave solutions, and more specifically, on the speed of gene drive invasion (if successful). We considered various timings of gene conversion (in the zygote or in the germline) and different probabilities of gene conversion (instead of assuming 100[Formula: see text] conversion as done in a previous work). We compared the types of propagation when the intrinsic growth rate of the population takes extreme values, either very large or very low. When it is infinitely large, the wave can be either successful or not, and, if successful, it can be either pulled or pushed, in agreement with previous studies (extended here to the case of partial conversion). In contrast, it cannot be pushed when the intrinsic growth rate is vanishing. In this case, analytical results are obtained through an insightful connection with an epidemiological SI model. We conducted extensive numerical simulations to bridge the gap between the two regimes of large and low growth rate. We conjecture that, if it is pulled in the two extreme regimes, then the wave is always pulled, and the wave speed is independent of the growth rate. This occurs for instance when the fitness cost is small enough, or when there is stable coexistence of the drive and the wild-type in the population after successful drive invasion. Our model helps delineate the conditions under which demographic dynamics can affect the spread of a gene drive.


Spillover and crossover effects of exposure to work-related aggression and adversities: A dyadic diary study.
The past two decades have produced extensive evidence on the manifold and severe outcomes for victims of aggression exposure in the workplace. However, due to the dominating individual-centered approach, most findings miss a social network perspective. Consequently, knowledge of negative spillover to different life-domains or crossover to uninvolved individuals alongside a detailed understanding of the involved transmission processes remains scarce. By integrating social aggression theorizing, the present study investigated transmission routes (emphatic, behavioral) of experienced adversities and aggression at work toward perpetration of aggressive behavior and potential spillover and crossover effects into the private life domain in a diary study of 72 mixed dyads. Analyses of mediation based upon the Actor-Partner Interdependence Model revealed an association between the frequency of perpetrating aggressive behavior in the work context and a spillover into the private life domain via aggression-promoting internal states (emotions, cognitions, arousal). Based on the different patterns of mediation, it appears that adversities follow a mental transmission process, whereby experienced aggression displayed behavioral assimilation. In contrast, no crossover effects of exposure to adversities or aggression at work to a study partner at home could be detected. Practical and theoretical implications as well as limitations and ideas for future work are discussed.


Reduction of Pax9 gene dosage in an allelic series of mouse mutants causes hypodontia and oligodontia.
Missing teeth (hypodontia and oligodontia) are a common developmental abnormality in humans and heterozygous mutations of PAX9 have recently been shown to underlie a number of familial, non-syndromic cases. Whereas PAX9 haploinsufficiency has been suggested as the underlying genetic mechanism, it is not known how this affects tooth development. Here we describe a novel, hypomorphic Pax9 mutant allele (Pax9neo) producing decreased levels of Pax9 wild-type mRNA and show that this causes oligodontia in mice. Homozygous Pax9neo mutants (Pax9neo/neo) exhibit hypoplastic or missing lower incisors and third molars, and when combined with the null allele Pax9lacZ, the compound mutants (Pax9neo/lacZ) develop severe forms of oligodontia. The missing molars are arrested at different developmental stages and posterior molars are consistently arrested at an earlier stage, suggesting that a reduction of Pax9 gene dosage affects the dental field as a whole. In addition, hypomorphic Pax9 mutants show defects in enamel formation of the continuously growing incisors, whereas molars exhibit increased attrition and reparative dentin formation. Together, we conclude that changes of Pax9 expression levels have a direct consequence for mammalian dental patterning and that a minimal Pax9 gene dosage is required for normal morphogenesis and differentiation throughout tooth development.


Sensing wave-front amplitude and phase with phase diversity.
We show in benchtop experiments that wave-front phase estimation by phase diversity can be significantly improved by simultaneous amplitude estimation. Processing speed, which will be important for real-time wave-front control applications, can be enhanced by use of small-format detectors with pixels that do not fully sample the diffraction limit. Using an object-independent phase-diversity algorithm, we show that, for both pointlike and extended objects, the fidelity of the phase and amplitude estimates degrades gracefully, rather than catastrophically, as the sampling becomes coarser. We show in simulation that the same algorithm also improves the fidelity of image reconstruction of complex targets.


Deep reinforcement learning for modeling human locomotion control in neuromechanical simulation.
Modeling human motor control and predicting how humans will move in novel environments is a grand scientific challenge. Researchers in the fields of biomechanics and motor control have proposed and evaluated motor control models via neuromechanical simulations, which produce physically correct motions of a musculoskeletal model. Typically, researchers have developed control models that encode physiologically plausible motor control hypotheses and compared the resulting simulation behaviors to measurable human motion data. While such plausible control models were able to simulate and explain many basic locomotion behaviors (e.g. walking, running, and climbing stairs), modeling higher layer controls (e.g. processing environment cues, planning long-term motion strategies, and coordinating basic motor skills to navigate in dynamic and complex environments) remains a challenge. Recent advances in deep reinforcement learning lay a foundation for modeling these complex control processes and controlling a diverse repertoire of human movement; however, reinforcement learning has been rarely applied in neuromechanical simulation to model human control. In this paper, we review the current state of neuromechanical simulations, along with the fundamentals of reinforcement learning, as it applies to human locomotion. We also present a scientific competition and accompanying software platform, which we have organized to accelerate the use of reinforcement learning in neuromechanical simulations. This "Learn to Move" competition was an official competition at the NeurIPS conference from 2017 to 2019 and attracted over 1300 teams from around the world. Top teams adapted state-of-the-art deep reinforcement learning techniques and produced motions, such as quick turning and walk-to-stand transitions, that have not been demonstrated before in neuromechanical simulations without utilizing reference motion data. We close with a discussion of future opportunities at the intersection of human movement simulation and reinforcement learning and our plans to extend the Learn to Move competition to further facilitate interdisciplinary collaboration in modeling human motor control for biomechanics and rehabilitation research.


Imaging of the pituitary and sella turcica.
The pituitary gland is housed in the sella turcica and has vital endocrinologic functions. It lies in close proximity to numerous vital structures, including the optic chiasm, sphenoid sinus, cavernous sinus and hypothalamus. An understanding of the function, anatomy and embryology of the pituitary gland and its surrounding structures is vital to understanding its normal appearance, as well as in evaluating the broad spectrum of pathology that can involve the pituitary gland. Imaging of pathology in the sellar region, including pituitary adenomas, meningiomas, craniopharyngiomas and aneurysms, plays an important role in guiding treatment decisions. Modern imaging techniques are also important in evaluating the pituitary gland after surgery.


Cerebral Haemodynamics: Effects of Systemic Arterial Pulsatile Function and Hypertension.
Concepts of pulsatile arterial haemodynamics, including relationships between oscillatory blood pressure and flow in systemic arteries, arterial stiffness and wave propagation phenomena have provided basic understanding of underlying haemodynamic mechanisms associated with elevated arterial blood pressure as a major factor of cardiovascular risk, particularly the deleterious effects of isolated systolic hypertension in the elderly. This topical review assesses the effects of pulsatility of blood pressure and flow in the systemic arteries on the brain. The review builds on the emerging notion of the "pulsating brain", taking into account the high throughput of blood flow in the cerebral circulation in the presence of mechanisms involved in ensuring efficient and regulated cerebral perfusion. Recent studies have provided evidence of the relevance of pulsatility and hypertension in the following areas: (i) pressure and flow pulsatility and regulation of cerebral blood flow, (ii) cerebral and systemic haemodynamics, hypertension and brain pathologies (cognitive impairment, dementia, Alzheimer's disease), (iii) stroke and cerebral small vessel disease, (iv) cerebral haemodynamics and noninvasive estimation of cerebral vascular impedance, (v) cerebral and systemic pulsatile haemodynamics and intracranial pressure, (iv) response of brain endothelial cells to cyclic mechanical stretch and increase in amyloid burden. Studies to date, producing increasing epidemiological, clinical and experimental evidence, suggest a potentially significant role of systemic haemodynamic pulsatility on structure and function of the brain.


Survivors' perspectives on the impact of clergy sexual abuse on families of origin.
Clergy-perpetrated sexual abuse rose to public attention in 2002 through the disclosure of abuse by Catholic priests within the Archdiocese of Boston and a simultaneous cover-up by church hierarchy. Similar patterns have since been described in other Catholic dioceses and in other faith denominations. While recent studies have examined the impact of such abuse on adult survivors, little is known about the impact on their families of origin. Using the Trauma Transmission and Empowerment models and the Family Adjustment and Adaptation Response model, this paper examines the impact of such abuse on families from male survivors' perspectives. A five-phased approach to reconciliation within families and dialogue with the church community is discussed to highlight communication as a core theme to healing.


Deep metagenome and metatranscriptome analyses of microbial communities affiliated with an industrial biogas fermenter, a cow rumen, and elephant feces reveal major differences in carbohydrate hydrolysis strategies.
The diverse microbial communities in agricultural biogas fermenters are assumed to be well adapted for the anaerobic transformation of plant biomass to methane. Compared to natural systems, biogas reactors are limited in their hydrolytic potential. The reasons for this are not understood. In this paper, we show that a typical industrial biogas reactor fed with maize silage, cow manure, and chicken manure has relatively lower hydrolysis rates compared to feces samples from herbivores. We provide evidence that on average, 2.5 genes encoding cellulolytic GHs/Mbp were identified in the biogas fermenter compared to 3.8 in the elephant feces and 3.2 in the cow rumen data sets. The ratio of genes coding for cellulolytic GH enzymes affiliated with the Firmicutes versus the Bacteroidetes was 2.8:1 in the biogas fermenter compared to 1:1 in the elephant feces and 1.4:1 in the cow rumen sample. Furthermore, RNA-Seq data indicated that highly transcribed cellulases in the biogas fermenter were four times more often affiliated with the Firmicutes compared to the Bacteroidetes, while an equal distribution of these enzymes was observed in the elephant feces sample. Our data indicate that a relatively lower abundance of bacteria affiliated with the phylum of Bacteroidetes and, to some extent, Fibrobacteres is associated with a decreased richness of predicted lignocellulolytic enzymes in biogas fermenters. This difference can be attributed to a partial lack of genes coding for cellulolytic GH enzymes derived from bacteria which are affiliated with the Fibrobacteres and, especially, the Bacteroidetes. The partial deficiency of these genes implies a potentially important limitation in the biogas fermenter with regard to the initial hydrolysis of biomass. Based on these findings, we speculate that increasing the members of Bacteroidetes and Fibrobacteres in biogas fermenters will most likely result in an increased hydrolytic performance.


A Cas12a-based gene editing system for Phytophthora infestans reveals monoallelic expression of an elicitor.
Phytophthora infestans is a destructive pathogen of potato and a model for investigations of oomycete biology. The successful application of a CRISPR gene editing system to P. infestans is so far unreported. We discovered that it is difficult to express CRISPR/Cas9 but not a catalytically inactive form in transformants, suggesting that the active nuclease is toxic. We were able to achieve editing with CRISPR/Cas12a using vectors in which the nuclease and its guide RNA were expressed from a single transcript. Using the elicitor gene Inf1 as a target, we observed editing of one or both alleles in up to 13% of transformants. Editing was more efficient when guide RNA processing relied on the Cas12a direct repeat instead of ribozyme sequences. INF1 protein was not made when both alleles were edited in the same transformant, but surprisingly also when only one allele was altered. We discovered that the isolate used for editing, 1306, exhibited monoallelic expression of Inf1 due to insertion of a copia-like element in the promoter of one allele. The element exhibits features of active retrotransposons, including a target site duplication, long terminal repeats, and an intact polyprotein reading frame. Editing occurred more often on the transcribed allele, presumably due to differences in chromatin structure. The Cas12a system not only provides a tool for modifying genes in P. infestans, but also for other members of the genus by expanding the number of editable sites. Our work also highlights a natural mechanism that remodels oomycete genomes.


Acute toxicity of dispersed crude oil on the cold-water copepod Calanus finmarchicus: Elusive implications of lipid content.
In this investigation, acute toxicity data were used from two previously reported studies where cold-water copepods were exposed to mechanically dispersed (MD) and chemically (CD) dispersed oil. In one of these studies, concentration-dependent mortality was observed, whereas no apparent relationship between exposure concentration and mortality was found in the other. The only marked difference between the studies is that copepods in the first experiment displayed a lower lipid sac volume (on average) than in the second one. In this study additional biometric data on lipid content were utilized and observed effects and toxicokinetics modeling applied in order to investigate whether differences in sensitivity between copepod cohorts might be explained by differences in lipid content. Results suggest that although a considerable lipid sac might retard toxicokinetics, the observed differences in lipid volume are not sufficient to explain differences in toxicity. Further, there are no apparent indications that acute toxic stress leads to lipid depletion, or that acute increased mortality rate selectively affects lipid-poor individuals. It is conceivable that other potential explanations exist, but the causal relationship between lipid content and increased mortality frequency remains elusive.


Synergy of Adsorption and Photocatalytic Reduction for Efficient Removal of Cr(VI) with Polyvinylidene Fluoride@Polyvinyl Alcohol-FeC2O4/Bi2.15WO6.
Although the photocatalytic reduction of Cr(VI) to Cr(III) by traditional powder photocatalysts is a promising method, the difficulty and poor recovery of photocatalysts from water hinder their wide practical applications. Herein, we present that FeC2O4/Bi2.15WO6 (FeC2O4/BWO) composites were tightly bonded to modified polyvinylidene fluoride (PVDF) membranes by chemical grafting with the aid of polyvinyl alcohol (PVA) to form photocatalytic composite membranes (PVDF@PVA-FeC2O4/BWO). The contact angle of PVDF@PVA-FeC2O4/BWO (0.06 wt % of FeC2O4/BWO) is 48.0°, which is much lower than that of the pure PVDF membrane (80.5°). Meanwhile, the permeate flux of 61.43 g m-2 h-1 and water flux of 250.60 L m-2 h-1 were observed for PVDF@PVA-FeC2O4/BWO composite membranes. The tensile strength of composite membranes reached 48.84 MPa, which was 9.8 times higher than that of PVDF membrane. It was found that the PVDF@PVA-FeC2O4/BWO membrane exhibited excellent photocatalytic Cr(VI) reduction performance under both simulated and real sunlight irradiation. The adsorption for Cr(VI) by PVDF@PVA-FeC2O4/BWO can reach 47.6% in the dark process within 30 min, and the removal percentage of Cr(VI) could reach 100% with a rate constant k value of 0.2651 min-1 after 10 min of light exposure, indicating a synergistic effect of adsorption and photoreduction for Cr(VI) removal by the composite membrane. The PVDF@PVA-FeC2O4/BWO membrane had good stability and reusability after seven consecutive cycles. Most importantly, the influences of foreign ions on Cr(VI) reduction were investigated to mimic real sewage, which revealed that no obvious adverse effects can be found with the presence of common foreign ions in sewage. The photocatalytic membrane material developed in this study provides a new idea for treating Cr(VI)-containing wastewater and has a more significant application prospect.


The impact of the hepatitis B virus vaccine on the incidence of hepatitis B virus-associated membranous nephropathy.
The hepatitis B virus (HBV) vaccine has resulted in a decline in the incidence of HBV carriage and hepatocellular carcinoma in southeast Asia. Vaccine efficacy in Africa has not been adequately assessed. To report on the impact of HBV vaccination in South Africa on HBV-associated membranous nephropathy (MN) over 6 years. King Edward VIII Hospital in Durban is the only tertiary referral center for the province of KwaZulu-Natal for children with renal diseases. The HBV vaccine was introduced into the South African Expanded Programme on Immunisation on April 1, 1995; vaccine coverage rates between April 1, 1995, and December 31, 2001, for children for the first, second, and third doses were 85.4%, 78.2%, and 62.0%, respectively. Hepatitis B virus status was determined using a radioimmunoassay (January 1, 1984-March 31, 1991) or an enzyme-linked immunosorbent assay. Membranous nephropathy was confirmed by the results of a renal biopsy. The hospital average annual incidence of HBV-associated MN was compared before and after vaccination and according to age groups. Between January 31, 1984, and December 31, 2001, there were 119 children with HBV-associated MN; their mean age was 7 years (range, 1-14 years), and 101 (84.9%) were males. The average annual rate ratio per 105 child population was 0.25. The overall incidence rate ratio showed a significant decrease from January 1, 2000, to December 31, 2001, compared with the preimmunization period (January 1, 1984-December 31, 1994) (incidence rate ratio, 0.12; 95% confidence interval, 0.03-0.50). Children from birth to the age of 4 years experienced no disease after 1998. Children aged 5 to 10 years showed a significant decrease in 2000-2001 compared with the prevaccination years (incidence rate ratio, 0.19; 95% confidence interval, 0.05-0.80). The HBV vaccine, even at low coverage for the full South African Expanded Programme on Immunisation schedule, reduced the hospital incidence of HBV-associated MN over 6 years.


A Series of Enthalpically Optimized Docetaxel Analogues Exhibiting Enhanced Antitumor Activity and Water Solubility.
A dual-purpose strategy aimed at enhancing the binding affinity for microtubules and improving the water solubility of docetaxel led to the design and synthesis of a series of C-2- and C-3'-modified analogues. Both aims were realized when the C-3' phenyl group present in docetaxel was replaced with a propargyl alcohol. The resulting compound, 3f, was able to overcome drug resistance in cultured P-gp-overexpressing tumor cells and showed greater activity than docetaxel against drug-resistant A2780/AD ovarian cancer xenografts in mice. In addition, the considerably lower hydrophobicity of 3f relative to both docetaxel and paclitaxel led to better aqueous solubility. A molecular model of tubulin-bound 3f revealed novel hydrogen-bonding interactions between the propargyl alcohol and the polar environment provided by the side chains of Ser236, Glu27, and Arg320.


Cluster of Norovirus Genogroup IX Outbreaks in Long-Term Care Facilities, Utah, USA, 2021.
We report 5 clustered acute gastroenteritis outbreaks in long-term care facilities in Utah, USA, that were linked to healthcare employees working at multiple facilities. Four outbreaks were caused by norovirus genotype GIX. We recommend continued norovirus surveillance and genotyping to determine contributions of this genotype to norovirus outbreaks.


Adsorptive removal of gallic acid from aqueous solution onto magnetic ion exchange resin.
Finding an appropriate adsorbent with high adsorption capacity, quick adsorption kinetics and easy regeneration was crucial to the removal of gallic acid (GA) from water and wastewater. Our aims were to investigate whether a magnetic ion exchange (MIEX) resin had the three merits mentioned above, and investigate the feasibility of GA adsorption on MIEX resin, and the adsorption kinetics, equilibrium, thermodynamics, regeneration and mechanism using batch tests. The uptake of GA increased with increasing GA concentration. The GA concentration influenced the time needed to reach equilibrium, but the adsorption could be completed within 120 min. Elevating temperature facilitated the GA removal. The removal percent remained above 95.0% at pH 5.0-11.0. Carbonate and bicarbonate promoted the GA removal; conversely chloride, sulfate and nitrate restrained the GA removal significantly. The adsorption kinetics could be fitted well with the pseudo second-order model, and the film diffusion governed the whole adsorption rate. The equilibrium data followed the Redlich-Peterson isotherm model. The adsorption was a spontaneous, endothermic and entropy driven process. The ion exchange dominated the removal mechanism. The spent MIEX resin was well regenerated by sodium chloride. Therefore, MIEX resin is a potential adsorbent for removing GA quickly and efficiently from water and wastewater.


Microleakage of four different restorative glass ionomer formulations in class V cavities: Er:YAG laser versus conventional preparation.
To investigate microleakage in class V cavities following restoration with conventional glass-ionomer cements (CGICs) or resin-modified glass-ionomer cements (RMGICs), following Er:YAG laser or conventional preparation. The sealing ability of GICs in Er:YAG-lased cavities has not been studied extensively. Three hundred and twenty class V cavities were assigned to four groups: those in groups A and B were prepared using an Er:YAG laser, and those in groups C and D were conventionally prepared. In groups B and D the surface was additionally conditioned with cavity conditioner. Each group was subdivided according to the GIC used: groups 1 (Fuji II), 2 (Fuji IX), 3 (Fuji II LC) and 4 (Fuji VIII). After thermocycling, the specimens were immersed in a 2% methylene blue solution, sectioned oro-facially, and analyzed for leakage. The effect of the conditioner was analyzed using a scanning electron microscope (SEM). Significant differences between occlusal and gingival margins were found in all groups (p < 0.05) except B4, D3, and D4. Comparison of preparation methods (groups A-D) revealed significant differences at the occlusal margin in groups 1 and 3, but in all groups at the gingival margin (p < 0.05). Laser preparation without conditioning allowed more leakage (p < 0.05). Comparison of filling materials (groups 1-4) revealed significant differences in groups B and C at the occlusal margin, and in all groups at the gingival margin (p < 0.05). In these groups, laser-prepared cavities (with or without conditioning) restored with Fuji II LC and Fuji VIII showed the least leakage at both margins. RMGICs allowed less microleakage than CGICs. Complete marginal sealing was not achieved and conditioning is recommended.


'I just want to be a grandmother, not a caregiver for their kids' Perceptions of childminding among Pacific grandparents living in Aotearoa, New Zealand.
A growing body of research indicates both positive and negative effects of grandparent childcare; effects that are largely dependent upon the context and intensity of the care are required. Here, we suggest that context to be inclusive of cultural background. Drawing on the indigenous methodological framework, talanoa, the views of 13 Pacific Island grandparents in relation to themes of grandparent childminding are explored, as well its proximity to perceptions of elder abuse. A cultural analysis reveals that traditions specific to the Pacific way of life may lead to increased risk of prolonged childcare. The participants in this study felt that prolonged childminding deprived them of time which could be used to benefit them and their community in the long run. It was viewed as a form of disrespect, as older people are revered and held in high regard in decision making activities from the Pacific worldview. The participants embraced their roles as the knowledge holders of cultural treasures; responsible for teaching children and grandchildren their genealogy and language, and for upholding the protocols of their cultural heritage. However, they felt their contributions were not reciprocated nor valued, but instead exploited.


A Unique Cause of Upper Airway Obstruction in a Child: Laryngeal Lipoma.
There are lots of diseases causing pediatric upper airway obstruction and stridor. They can be both congenital or acquired. While congenital causes are laryngomalacia, vocal cord palsy, congenital subglottic stenosis, acquired ones range from infections to foreign bodies or neoplasms. Laryngeal neoplasms develop almost epithelial in origin. Non-epithelial tumors consist 1% of laryngeal neoplasms. Although lipoma is the most common soft tissue tumor, laryngeal involvement is very rare and seen in the ages between 40-60 years. A 13-month-old child who had laryngeal lipoma and upper airway obstruction was aimed to present in this paper.


Modeling the effect of blunt impact on mitochondrial function in cartilage: implications for development of osteoarthritis.
Osteoarthritis (OA) is a disease characterized by degeneration of joint cartilage. It is associated with pain and disability and is the result of either age and activity related joint wear or an injury. Non-invasive treatment options are scarce and prevention and early intervention methods are practically non-existent. The modeling effort presented in this article is constructed based on an emerging biological hypothesis-post-impact oxidative stress leads to cartilage cell apoptosis and hence the degeneration observed with the disease. The objective is to quantitatively describe the loss of cell viability and function in cartilage after an injurious impact and identify the key parameters and variables that contribute to this phenomenon. We constructed a system of differential equations that tracks cell viability, mitochondrial function, and concentrations of reactive oxygen species (ROS), adenosine triphosphate (ATP), and glycosaminoglycans (GAG). The system was solved using MATLAB and the equations' parameters were fit to existing data using a particle swarm algorithm. The model fits well the available data for cell viability, ATP production, and GAG content. Local sensitivity analysis shows that the initial amount of ROS is the most important parameter. The model we constructed is a viable method for producing in silico studies and with a few modifications, and data calibration and validation, may be a powerful predictive tool in the search for a non-invasive treatment for post-traumatic osteoarthritis.


P044 A Profile of New Start IBD Patients on Multiple Advanced/Biologic Therapies.
After analyzing patient chart data from nearly 1,000 recently-initiated biologic/JAK inhibitor inflammatory bowel disease (IBD) patients, it was discovered that 6% are treated with multiple advanced/biologic therapies. This analysis sought to profile those new start patients on a multi-biologic/JAK inhibitor regimen against those treated with a single advanced therapy to determine the type of patient who is typically initiated on more than one advanced/biologic therapy, and why the combination is necessary. An independent market analytics firm collaborated with US gastroenterologists (n=197) to conduct a retrospective chart review of patients with inflammatory bowel disease (IBD) (n=999) who were started on a biologic agent for the first time. Gastroenterologists submitted patient-level data via a HIPAA-compliant audit form which included both clinical and non-clinical data. The data were collected and analyzed in April-June 2021. 7% of ulcerative colitis (UC) and 5% of Crohn's disease (CD) patients are currently treated with more than one biologic/JAK inhibitor. The most common therapy used in combination with another for UC is adalimumab (36%), followed by infliximab brand (18%), and ustekinumab (18%). For CD, the most common combinations involve infliximab brand (35%), followed by vedolizumab (22%), and ustekinumab (13%). The necessity for multiple biologic therapy is clarified when reviewing the IBD patients' comorbidities and medical history. The prevalence of ulcerative proctitis (34% vs. 11%) and gastroduodenal CD (43% vs. 4%) among multi-biologic/JAK inhibitor patients is higher than among those treated with one biologic/JAK inhibitor. Additionally, multi-biologic/JAK inhibitor patients have an increased prevalence of recent bowel perforation (16% vs. 1%) and surgical bowel re-section (10% vs. 3%) compared to those treated with just one advanced therapy. Due to this more severe disease profile, patients treated with more than one advanced/biologic therapy are more likely to report severe impairment in work performance (48% vs. 34%), chronic fatigue comorbidity (23% vs. 5%), more frequent ER visits per year (average= 2.3 vs. 1.1), and more frequent hospitalizations per year (2.0 vs. 0.6). A profile of new start biologic IBD patients ideal for concomitant advanced therapy emerged when reviewing almost 1,000 physician-reported patient records. These patients are more likely to have had gastroduodenal Crohn's disease and or recent bowel perforation or re-section. These patients are more likely to report impaired work performance, chronic fatigue, more frequent ER visits and more frequent hospitalizations.


[A case of multiple skin metastases from cancer of the descending colon responding to FOLFIRI/cetuximab therapy].
A 64-year-old woman presented to our hospital with subcutaneous tumors in the right thoracic region. After undergoing a thorough medical evaluation, she was diagnosed with multiple skin metastases arising from cancer of the descending colon. Surgical resection of the primary lesion was performed and FOLFIRI (5-fluorouracil, levofolinate calcium, irinotecan) and cetuximab chemotherapy for the metastases was initiated. The patient subsequently entered remission and did not experience any major side effects. This case report details an effective therapy for colon cancer with multiple skin metastases and presents a discussion of the expression profiles of epidermal growth factor receptor in both the primary and metastatic lesions.


"Social capital," GNP per capita, relative income, and health: an ecological study of 23 countries.
The effects of social capital, income inequality, and absolute per capita income were investigated in an ecological analysis of 23 rich and poor countries. Trust was chosen as an indicator of social capital, and GNP (gross national product) per capita and Gini index measured absolute and relative income, respectively. These independent variables were analyzed in a linear regression model with the dependent variables adult mortality rate (25-64 years), life expectancy, and infant mortality rate (IMR). Separate analyses were performed for poor and rich countries as well as all countries combined. Social capital (trust) showed no significant association with the three health outcomes. A particularly strong relationship was found between Gini index and IMR for rich countries, and GNP per capita and life expectancy for all countries. In the group of poor countries, GNP per capita and Gini index in the same model were associated with IMR. The results contradict the suggested impact of social capital on health, and instead support the notion that economic factors such as absolute income and relative income distribution are of importance.


Treatment of chronic diarrhoea: loperamide versus ispaghula husk and calcium.
Twenty-five patients with chronic diarrhoea were included in an open, randomized crossover trial comparing the effect of loperamide with ispaghula and calcium. Nineteen patients completed both treatments. Before treatment the median number of daily stools was 7 (range, 4-13), stool consistency was loose in all, and urgency was present in 16 out of 19 patients. Both treatments halved stool frequency, but with regard to urgency and stool consistency ispaghula and calcium was significantly better. A combination of ispaghula and calcium seems to be a cheap and effective alternative to conventional treatment of chronic diarrhoea. Moreover, side effects were minimized.


Asbestos identification by dispersion staining microscopy.
Asbestos can be detected and identified by an optical microscope procedure known as dispersion staining. This procedure can be carried out with most phase contrast equipped microscopes. The primary application is for material samples. Distinction between tremolite and anthophyllite asbestos requires examination between crossed polarizers.


A search for an essential function of the replication origin ARS1 in the life cycle of Saccharomyces cerevisiae.
We have investigated the significance of the chromosomal replication origin, ARS1, during the entire life cycle of yeast. This was done by substituting the chromosomal copy with a series of ars1 deletion mutants. It was shown that the ARS1 replication origin is not essential for mitotic or premeiotic DNA replication since no effect on growth, chromosomal loss rate and spore viability was observed in the ars1 mutant strains. We conclude that replication origins are abundantly, present in the yeast genome and that the removal of a single replication origin is compensated for by replication forks emanating from neighbouring origins.