Disposable FFP2 and Type IIR Medical-Grade Face Masks: An Exhaustive Analysis into the Leaching of Micro- and Nanoparticles and Chemical Pollutants Linked to the COVID-19 Pandemic.

The COVID-19 pandemic has increased the worldwide production and use of disposable plastic face masks (DPFMs). The release of micro- and nanopollutants into the environment is one of the impacts derived from regulated and unregulated disposal of DPFMs. This study focuses on the emission of pollutants from medical-grade DPFMs when submerged in deionized water, simulating regulated and unregulated disposal of these masks. Three brands of FFP2 and three brands of Type IIR medical masks, produced in various countries (UK, EU, and non-EU), were investigated. Field emission gun scanning electron microscopy (FEG-SEM) was used to obtain high-resolution images of the micro- and nanoparticles, and 0.02 µm pore size inorganic membranes were used to retain and subsequently analyze smaller particle size nanoparticles (>20 nm) released from the DPFMs. Particles and fibers in the micro- and nanoscale were found in all six DPFM brands. SEM with energy-dispersive spectroscopy analysis revealed the presence of particles containing different heavy metals like lead, mercury, and arsenic. Inductively coupled plasma mass spectrometry analysis confirmed the leaching of trace heavy metals to water (antimony up to 2.41 µg/L and copper up to 4.68 µg/L). Liquid chromatography-mass spectrometry analysis identified polar organic species related to plastic additives and contaminants such as polyamide-66 monomers and oligomers.

Environmental condition alters amphetamine self-administration: role of the MGluR5 receptor and schedule of reinforcement.

RATIONALE: Evidence suggests that differential rearing influences the function of a receptor subtype critical for maintaining glutamate homeostasis. Maintaining homeostatic glutamatergic function may be an important protector against drug abuse. OBJECTIVE: This study sought to determine if differential rearing influences the function of a receptor critical for glutamate homeostasis, which could in turn affect rates of amphetamine self-administration. METHODS: Rats were assigned to enriched (EC), isolated (IC), or standard (SC) conditions. After rearing for 30 days, rats were trained to lever press for sucrose reinforcement before the implantation of indwelling jugular catheters. After reaching stable responding for amphetamine (0.03 or 0.1 mg/kg/infusion), rats were injected with five doses (0, 0.3, 1.0, 3.0, and 5.0 mg/kg) of the mGluR5 antagonist, 3-((2-methyl-1,3-thiazol-4-yl)ethynyl) pyridine hydrochloride (MTEP), 30 min before self-administration sessions. Following fixed-ratio (FR-1) testing, rats were administered identical doses of MTEP on a progressive-ratio (PR) reinforcement schedule. RESULTS: MTEP (3.0 mg/kg) attenuated FR-1 self-administration (0.03 mg/kg/infusion) in IC rats. MTEP also dose-dependently attenuated amphetamine self-administration (0.1 mg/kg/infusion) during FR-1 and PR sessions, with 5.0 mg/kg MTEP attenuating amphetamine self-administration in IC and SC rats and 3.0 mg/kg MTEP attenuating amphetamine self-administration in EC and SC rats. PR results also revealed that IC rats not treated with MTEP were more motivated to self-administer the higher dose of amphetamine. CONCLUSIONS: These results suggest that the mGlu5 receptor mediates differences in drug-taking behavior among differentially reared rats. Isolation also decreased sensitivity to MTEP, suggesting that environmental factors alter glutamate homeostasis which subsequently affects sensitivity and motivation to self-administer amphetamine.

Anabolic steroids for the treatment of weight loss in HIV-infected individuals.

BACKGROUND: Individuals with HIV infection often lose weight during the course of their disease. Furthermore, low serum concentrations of testosterone are common in individuals with HIV infection, particularly those with weight loss. Treatment of weight loss with anabolic steroids in HIV-infected individuals may be beneficial. OBJECTIVES: Our objectives were to assess the efficacy and safety of anabolic steroids for the treatment of weight loss in adults with HIV infection. SEARCH STRATEGY: We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, AIDSLINE, AIDSearch, EMBASE, CINAHL, Current Contents, and the National Library of Medicine Gateway Abstracts for controlled trials up to April 2005. We also searched the bibliographies of the identified studies and review the articles. In addition, pharmaceutical manufacturers of anabolic steroids were contacted. SELECTION CRITERIA: Randomized controlled trials that compared the use of an anabolic steroid to placebo to treat weight loss in adults with HIV were included. Randomized controlled trials that compared the use of anabolic steroids to placebo for the treatment of weight loss in adults with HIV were selected. Change from baseline in lean body mass or in body weight was reported as on outcome measure. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trials for quality of randomization, blinding, withdrawals, and adequacy of allocation concealment. For continuous data, weighted mean differences (WMD) were calculated. For dichotomous outcomes, risk differences, were calculated. Because of uncertainty as to whether consistent true effects exist in such different populations and treatments, the authors decided a priori to use random effects models for all outcomes. MAIN RESULTS: Thirteen trials met the inclusion criteria. Two hundred ninety-four individuals randomized to anabolic steroid therapy and 238 individuals randomized to placebo were included in the analysis of efficacy for change from baseline in lean body mass. Three hundred forty-three individuals randomized to anabolic steroid and 286 randomized to placebo were included in the analysis of efficacy for change from baseline in body weight. The mean methodologic quality of the included studies was 4.1, of a maximum 5 points. Although significant heterogeneity was present for both outcomes, the average change in lean body mass was 1.3 kg (95% CI: 0.6, 2.0), while the average change in total body weight was 1.1 kg (95% CI: 0.3, 2.0). A total of eight deaths occurred during the treatment period; four in the anabolic steroid treatment groups and four in the placebo-treatment groups (risk difference 0.00, 95% CI -0.03, 0.03). The risk difference for withdrawals or discontinuations of study medication due to adverse events was 0.00 (95% CI: -0.02, 0.03). AUTHORS' CONCLUSIONS: Although the results of the trials were heterogeneous, on average, the administration of anabolic steroids appeared to result in a small increase in both lean body mass and body weight as compared with placebo. While these results suggest that anabolic steroids may be useful in the treatment of weight loss in HIV infected individuals, due to limitations, treatment recommendations cannot be made. Further information is required regarding the long-term benefit and adverse effects of anabolic steroid use, the specific populations for which anabolic steroid therapy may be most beneficial, and the optimal regime. In addition, the correlation of improvement in lean body mass with more clinically relevant endpoints, such as physical functioning and survival, needs to be determined.

Measuring systemic lupus erythematosus activity during pregnancy: validation of the lupus activity index in pregnancy scale.

OBJECTIVE: To validate the Lupus Activity Index in Pregnancy (LAI-P) scale as a diagnostic tool for lupus flares during pregnancy and the puerperium. METHODS: The LAI-P is a modified activity scale specific for pregnancy. Thirty-eight pregnant women with systemic lupus erythematosus (SLE) were prospectively followed in 3 clinics specific for lupus in pregnancy. On each visit, LAI-P was calculated. A modified physician global assessment (m-PGA) scale was used as gold standard (0 = no activity, 1 = mild-moderate activity, 2 = severe activity). A change > or = 0.25 in LAI-P was predefined as a flare according to previous studies in nonpregnant patients. For the purposes of the study, each visit was considered as an independent case. RESULTS: During the study period, 158 visits took place for a total 621 patient-weeks. Sensitivity to change was high (standardized response mean for LAI-P = 1.6). We found a significant association between LAI-P and m-PGA (P < 0.002 in all regression models performed). Sensitivity, specificity, and positive and negative predictive values were 0.93, 0.98, 0.88, and 0.99. Positive and negative likelihood ratios were 49 and 0.07, respectively. CONCLUSIONS: LAI-P has a high sensitivity to changes in lupus activity, a significant correlation with m-PGA, and high sensitivity, specificity, predictive values, and likelihood ratios for diagnosing SLE flares during pregnancy and the puerperium.

Measurement of decay parameters for Xi- --> Lambda pi- decay.

Based on 1.35 x 10(6) polarized Xi(-) events, we measure the parameter phi(Xi) to be -1.61 degrees +/-2.66 degrees +/-0.37 degrees for the Xi(-)-->Lambda pi(-) decay. New results for the parameters beta(Xi) and gamma(Xi) are also presented. Assuming that the CP-violating phase difference is negligible, we deduce the strong phase difference between the P-wave and S-wave amplitudes of the Lambda pi final state to be 3.17 degrees +/-5.28 degrees +/-0.73 degrees, reducing the uncertainty in estimating the level of CP violation in Xi-hyperon decay.

Item-cued directed forgetting of related words and pictures in children and adults: selective rehearsal versus cognitive inhibition.

The main purpose of this study was to compare the relative importance of selective rehearsal and cognitive inhibition in accounting for developmental changes in the directed-forgetting paradigm developed by R. A. Bjork (1972). In two experiments, children in Grades 2 and 5 and college students were asked to remember some words or pictures and to forget others when items were categorically related. Their memory for both items and the associated remember or forget cues was then tested with recall and recognition. Fifth graders recognized more of the forget-cued words than college students did. The pattern of results suggested that age differences in rehearsal and source monitoring (i.e., remembering whether a word had been cued remember or forget) were better explanatory mechanisms for children's forgetting inefficiencies than retrieval inhibition was. The results are discussed in terms of a multiple process view of inhibition.

Search for direct CP violation in nonleptonic decays of charged Xi and lambda hyperons

A search for direct CP violation in the nonleptonic decays of hyperons has been performed. In comparing the product of the decay parameters, alpha(Xi)alpha(Lambda), in terms of an asymmetry parameter, A(XiLambda), between hyperons and antihyperons in the charged Xi-->Lambdapi and Lambda-->ppi decay sequence, we found no evidence of direct CP violation. The parameter A(XiLambda) was measured to be 0.012+/-0.014.

New diagnostic tests for pulmonary embolism.

In 1990, the multicenter Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED), sponsored by the National Institutes of Health, compared the diagnostic value of the radioisotopic ventilation-perfusion lung scan (V/Q scan) with that of pulmonary angiography for the diagnosis of pulmonary embolism (PE). Despite the endurance of the radioisotopic V/Q scan as the most widely used test for evaluation of pulmonary embolism (PE), a better screening tool is clearly needed for use in the emergency department. During the past decade, several new modalities have emerged for evaluation of patients with suspected PE. We evaluate the diagnostic utility of the D-dimer test and the alveolar dead space determination as potential screening tests and of spiral computed tomography, magnetic resonance imaging, transthoracic echocardiography, and transesophageal echocardiography as potential confirmatory tests for PE. For comparison, recent data on the diagnostic utility of the alveolar-arterial oxygen gradient and the V/Q scan are included. The potential application of these new tests to a hypothetical ED population is described.

Clinical experience with combination disease-modifying antirheumatic drug therapy with cyclosporine.

OBJECTIVES: We previously reported on the clinical use of cyclosporine (Neoral), alone or in combination with methotrexate (MTX), in the first 46 refractory rheumatoid arthritis (RA) patients treated at our centre between March 1996 and November 1997. Thirty of the 46 patients remained on cyclosporine at study completion (mean dose 2.98 mg/kg/day) with efficacy inferred by significant reductions in the prednisolone and MTX doses and creatinine maintained in an acceptable range. Early discontinuation was primarily related to non-serious side effects. METHODS: The 30 patients continuing cyclosporine were reviewed 12 months later in November 1998. Analysis included life-table techniques. RESULTS: 21 of the original 46 patients (46%) continued at a mean dose of 2.59 mg/kg/day after a mean of 23.4 months. Nine patients discontinued cyclosporine during this 12-month period: 3 due to inactive disease, 2 due to hypertension, 2 due to elevated creatinine, and 1 due to mononeuritis multiplex secondary to rheumatoid vasculitis, and 1 due to inefficacy. Patients continuing cyclosporine had a shorter disease duration (9.85 versus 15.5 years [P = 0.05]). The prednisolone dose decreased from a baseline value of 10.57 mg/day to 6.78 mg/day (P = 0.007) and the MTX dose from 15.6 mg/week to 13.1 mg/week (P = 0.02). The mean serum creatinine level increased from a baseline of 73.86 mumol/l to 85.8 mumol/l (16%). 21/30 patients on combination therapy with MTX showed no difference in discontinuation rates compared with those on cyclosporine alone. Life-table analysis showed a bimodal distribution with significantly increased cyclosporine discontinuation in the first 12 months (principally due to non-renal/hypertensive causes) versus the subsequent period. CONCLUSION: This follow-up study indicates that the use of cyclosporine in refractory RA allows a reduction in the prednisolone and MTX doses. Utilization is longer in earlier disease and is unaffected by combination with MTX. Renal function is maintained within an acceptable range. The bimodal discontinuation curve reflects early patient/physician concern about minor side effects, while renal/hypertension changes resulted in later discontinuation.

The safety and efficacy of cyclosporine (Neoral) in rheumatoid arthritis.

OBJECTIVE: To assess the safety and efficacy of cyclosporine (Neoral), its steroid sparing effect, and its usefulness in combination therapy with methotrexate (MTX) in the treatment of refractory rheumatoid arthritis (RA). METHODS: All patients given cyclosporine for refractory RA over a 21 month period were included in an open, prospective study. Patients were reviewed initially fortnightly then monthly with clinical evaluation and serum creatinine. There were no restrictions on the use of other disease modifying agents, nonsteroidal antiinflammatory drugs, or corticosteroids. RESULTS: Forty-six patients with severe RA were included in the study, 33 (72%) female and 13 (28%) male, with a mean age of 54.8 years (range 20-74). At the completion of the study 30 (65%) were still taking cyclosporine at a mean dose of 2.94 mg/kg/day for a mean duration of 10.5 months. Thirteen patients discontinued cyclosporine due to side effects, most commonly gastrointestinal, and 3 due to inefficacy. Thirty-seven of the 46 patients were taking prednisolone at the start of the study at a mean dose of 10.36 mg/day, which decreased to 7.068 mg/day at the end of the study (p < 0.001). Thirty patients used cyclosporine in combination with MTX. The mean dose of MTX decreased from 15.08 to 13.67 mg/wk (p = 0.02). The mean serum creatinine increased by 13% from 74 to 83.7 micromol/l. Patients who continued therapy had a shorter duration of disease, with a mean of 9.93 years compared to 15.73 years in those who stopped therapy (p = 0.004). CONCLUSION: Cyclosporine (Neoral) was a safe and effective therapy in this population of patients with RA refractory to standard therapy. We observed a significant steroid sparing effect and have shown that combination therapy with MTX does not increase side effects and allows for a decrease in MTX dose. Renal function is not adversely affected if guidelines are followed.

The antiphospholipid antibody syndrome.

BACKGROUND: Recurrent miscarriages cause enormous distress and despair for sufferers. In a small number of patients this condition forms part of the antiphospholipid antibody syndrome. The anticardiolipin antibodies became quantifiable in 1983, which has meant that those suffering with this condition could be identified. OBJECTIVE: This article reviews the current understanding of this condition and offers an approach for managing patients with various components of this syndrome. DISCUSSION: The decision to screen for these antibodies is sometimes difficult as they can be presented in the normal population. However, by identifying the patient suffering with this condition, treatment can offered which may prevent a further miscarriage or a pregnant patient suffering a thromboembolic episode.

Pregnancy outcome in systemic lupus erythematosus (SLE): a review of 54 cases.

AIM: To compare the pregnancy outcome, in particular gestational age and birth weight in women with systemic lupus erythematosus (SLE) diagnosed before and after pregnancy, and to review data on presence or absence of the antiphospholipid (aPL) antibody and flares of disease activity. METHOD: Case histories were reviewed of women with a diagnosis of SLE and an obstetric event attending Monash Medical Centre (MMC) over an eight year period (1988-96). Fifty-four pregnancies in 28 women were studied, with 44 occurring after the diagnosis of SLE (Group 1) and ten prior to the diagnosis of SLE (Group 2). RESULTS: In Group 1 there were 25 live births (63%) with 16 full term and nine premature deliveries, 12 spontaneous abortions, three foetal deaths in utero and four elective terminations. In Group 2 there were seven live births (70%), two spontaneous abortions and one foetal death in utero. The mean gestational age of live births was 35.8 weeks and 39.2 weeks respectively (p < 0.001). The mean birth weight of live births was 2448 g and 3030 g respectively (p < 0.023). a PL antibodies were positive in eight of 26 women tested with three live births and were negative in 18 of 26 women with 12 live births. Flares of disease activity occurred in 17 of 28 pregnancies. CONCLUSION: Pregnancy in women with a predisposition to SLE have a high risk of an adverse outcome. Clinical disease confers an additional risk. The mean gestational age and birth weight were significantly less in women with established disease. Mild flares in disease activity resulted in a favourable outcome while renal flares had a worse outcome.

Acquired equivalence learning with antecedent and consequent unconditioned stimuli.

The conditions under which cues with similar training histories are treated by rats as being equivalent were examined. A significant event, food, either preceded, followed, or preceded and followed each of the Stimuli A and B; Stimulus C was not food-associated. Next, B was counterconditioned with footshock until it suppressed an appetitively motivated behavior. When A and C were tested for generalized suppression, A (treated like B) evoked more suppression than C (treated differently than B). However, this equivalence effect was strong only when A and B predicted food and were treated alike.

A single chain Fv fragment of P-glycoprotein-specific monoclonal antibody C219. Design, expression, and crystal structure at 2.4 A resolution.

A construct encoding a single chain variable fragment of the anti-P-glycoprotein monoclonal antibody C219 was made by combining the coding sequences for the heavy and light chain variable domains with a sequence encoding the flexible linker (GGGGS)3, an OmpA signal sequence, a c-myc identification tag, and a five-histidine purification tag. The construct was expressed in Escherichia coli and purified from the periplasmic fraction using a nickel chelate column and ion exchange chromatography. Three-step Western blot analysis showed that the construct retains binding affinity for P-glycoprotein. Crystals of 1.0 x 0.2 x 0.2 mm were grown in 100 mM citrate, pH 4.5, 21% polyethylene glycol 6000 in the presence of low concentrations of subtilisin, resulting in proteolytic removal of the linker and purification tags. The structure was solved to a resolution of 2.4 A with an R factor of 20.6, an Rfree of 28.5, and good stereochemistry. This result could lead to a clinically useful product based on antibody C219 for the diagnosis of P-glycoprotein-mediated multidrug resistance. The molecule will also be useful in biophysical studies of functional domains of P-glycoprotein, as well as studies of the intact molecule.

Factors associated with term low birthweight in Cardiff, Wales.

This project was undertaken to examine the associations of a number of risk factors with impaired fetal growth, exemplified by delivery of a low-birthweight infant at term (TLBW). Utilising a large database of largely homogeneous (white) births in Wales, the Cardiff Births Survey, multivariable analysis by logistic regression examined the relative importance of these risk variables. Significant independent associations with TLBW were found (in decreasing order of magnitude) for low maternal weight, pre-eclampsia, smoking, short maternal height, late pregnancy bleeding, early pregnancy bleeding, history of a previous stillbirth, primiparity and older maternal age. In this population, risk of TBLW was associated with a number of demographic, medical and social factors. Of these, only smoking is likely to be modified by intervention.

Crystallographic observation of a covalent catalytic intermediate in a beta-glycosidase.

The three-dimensional structure of a catalytically competent glycosyl-enzyme intermediate of a retaining beta-1,4-glycanase has been determined at a resolution of 1.8 A by X-ray diffraction. A fluorinated slow substrate forms an alpha-D-glycopyranosyl linkage to one of the two invariant carboxylates, Glu 233, as supported in solution by 19F-NMR studies. The resulting ester linkage is coplanar with the cyclic oxygen of the proximal saccharide and is inferred to form a strong hydrogen bond with the 2-hydroxyl of that saccharide unit in natural substrates. The active-site architecture of this covalent intermediate gives insights into both the classical double-displacement catalytic mechanism and the basis for the enzyme's specificity.