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.

Preliminary crystallographic analysis of a Fab specific for P-glycoprotein with and without bound peptide.

The antigen-binding fragment (Fab) of anti-peptide monoclonal antibody C219 raised against the multidrug resistance associated P-glycoprotein has been crystallized with and without bound peptide. The crystals of the Fab in the absence and presence of peptide belong to space groups P2(1) and P2(1)2(1)2(1), respectively. The volumes of both crystal forms are consistent with the presence of four Fab molecules per asymmetric unit. Diffraction data to 3.2 A resolution have been collected on a San Diego Multiwire Area Detector system from both crystal forms. Determination of the molecular replacement solutions is underway.

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.

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.

Stability of the amino acid content of nerve endings after administration of gamma-aminobutyrate agonists and antagonists.

The administration of GABA agonists or antagonists to mice resulted in unchanged levels of aspartate, glutamate, GABA and taurine in nerve endings (synaptosomes). On the other hand, agonist-induced increases in the levels of some of the amino acids occurred in locations other than the nerve endings. The GABA agonist SL75102 inhibited in vitro uptake of D-aspartate into synaptosomes, thereby raising the possibility that a similar phenomenon may cause an in vivo redistribution of glutamate and aspartate in brain tissue.

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.

Retinal vascular abnormalities in patients with coarctation of the aorta.

Pulsatile three-dimensional retinal arteriolar tortuosity has been previously reported in about 50% of patients with coarctation of the aorta. In a contemporary series of 20 patients with coarctation of the aorta, none exhibited this characteristic retinal vascular abnormality. Our findings suggest that the retinal vascular abnormalities in patients with coarctation of the aorta represent secondary hemodynamic changes. The prevalence of these abnormalities may be decreasing because of earlier surgical repair of coarctation.

Magnetic resonance imaging of the brain in isolated optic neuritis.

Magnetic resonance imaging of the brain was performed on ten patients who had isolated optic neuritis. Seven patients had abnormal images, with a distribution of lesions similar to that seen in multiple sclerosis, demonstrating subclinical dissemination in the central nervous system.

Corneal toxicity of propamidine.

Two patients with Acanthamoeba keratitis developed a corneal abnormality following prolonged treatment with topical 0.1% [corrected] propamidine isethionate. In both instances, withdrawal of drug therapy resulted in a gradual clearing of the keratopathy, with no permanent sequelae. The changes we observed may be confused with those of active Acanthamoeba infection.

The relationship of corneal epithelial defect size to drug penetration.

OBJECTIVE: To determine the relationship between corneal epithelial defect size and corneal penetration of a triazole antifungal drug in an animal model. METHODS: Corneas of adult rabbits were débrided of epithelium 25%, 50%, 75%, or 100% of surface area; the untreated fellow eye served as a control. Tritiated saperconazole was applied to each cornea every 5 minutes for 1 hour. The animals were killed and the cornea and aqueous of each eye were assayed for radiolabel activity. RESULTS: Removal of 25% of the corneal epithelium produced an increase in corneal saperconazole concentration compared with eyes with intact epithelium. Increasing epithelial defect size from 25% to 50% produced a ninefold increase in mean corneal drug concentration (P = .0001). There was no further increase in corneal drug levels in eyes with 75% or 100% epithelial defects. A similar threshold effect was observed in aqueous drug concentration between 25% and 50% débridement (P = .0001). CONCLUSION: In this experimental model, an apparent threshold was noted between 25% and 50% epithelial defect area, beyond which larger defects did not significantly increase drug penetration into the cornea or aqueous. This may be of clinical benefit in circumstances in which epithelial débridement is considered to enhance drug penetration.

Hereditary lymphedema and distichiasis.

Two patients with lymphedema-distichiasis syndrome illustrate that both Milroy's disease and late-onset hereditary lymphedema are sometimes associated with distichiasis. It is important for ophthalmologists to be aware of the lymphedema-distichiasis syndrome because of its ophthalmic manifestations and the associated systemic abnormalities that can be potentially life threatening.

Pharmacologic management of keratomycoses.

Fungal corneal infections can be very difficult to treat. An evolving understanding of the pharmacology of the currently available antifungal agents has led to improved medical treatment of the keratomycoses. The pharmacology, pharmacokinetics, spectrum of activity and toxicity of these agents is reviewed and promising new antifungal compounds and modes of treatment are discussed.

Late pulmonary allergic responses in actively but not passively IgE-sensitized rats.

Previous studies suggested that although rats that were passively sensitized [monoclonal murine immunoglobulin E (IgE)] would respond to pulmonary antigen challenge with an immediate increase in resistance, they exhibited no late increases in resistance, unlike late changes in rats actively sensitized to preferentially produce IgE antibody. We hypothesized that passively sensitized rats also would not develop antigen-induced pulmonary inflammation. In a blinded protocol we compared immediate responses and pulmonary resistance and inflammation at 8, 19 and 24 h after challenge with placebo antigen, with dinitrophenol-bovine serum albumin (DNP-BSA) to elicit a passively sensitized response, or with ovalbumin (OA) to elicit an actively sensitized response. Despite similar immediate responses to OA and DNP-BSA, only the rats challenged with OA had marked inflammatory changes and a significant incidence of late elevations in resistance. Inflammation scores and lung resistance were significantly correlated only in the OA group. We also observed that anesthesia with fentanyl/droperidol significantly attenuated the immediate but not the late responses to antigen challenge, compared with rats anesthetized with ketamine. We conclude that IgE-mediated immediate responses to pulmonary antigen challenge are insufficient, and may be unnecessary, to initiate antigen-induced late inflammatory changes.

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.

Traumatic wound dehiscence in pseudophakia.

In a series of 11 pseudophakic patients (11 eyes) who sustained wound dehiscence as a result of blunt trauma, five intraocular lenses were dislocated, one was fractured, and two were expulsed. Wound rupture occurred from three days to one year after surgery; the most common cause of injury was a fall. Iris prolapse was observed in all patients, with hyphema observed in seven. Vitreous prolapse occurred in four patients, and three patients developed retinal detachment. Six of the 11 patients had a visual acuity of 20/40 or better after repair. The limbal wound of a pseudophakic eye can dehisce as a consequence of blunt trauma long after surgery, and the position of the intraocular lens can be disrupted. Patients undergoing cataract extraction with intraocular lens implantation should be advised about the importance of long-term protective eyewear.

Cellular infiltration of the vitreous in a patient with X-linked immunodeficiency with increased IgM.

We studied visual impairment caused by benign lymphoid infiltration of the vitreous bilaterally, as a complication of a primary immunodeficiency, X-linked immunodeficiency with increased IgM in an 8-year-old boy. Immunophenotyping of a vitreous aspirate showed a mixed cell population, including lymphocytes (T helper, suppressor-cytotoxic T cells, and B cells) and macrophages. Cultures of the vitreous were negative for bacterial or fungal pathogens. The vitreous infiltrates have been resistant to treatment with corticosteroids and cytotoxic agents.

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.

Sterile corneal ulceration after cataract extraction in patients with collagen vascular disease.

We report the occurrence of sterile corneal ulceration in 11 eyes of eight patients with collagen vascular diseases and dry eyes after cataract extraction with intraocular lens implantation. Keratolysis occurred after both extracapsular and intracapsular cataract extraction and appeared unrelated to the type of intraocular lens. Despite aggressive lubrication and other medical treatment, including systemic immunosuppressive agents, penetrating keratoplasty was often required. Although all eyes were saved, visual outcome was usually poor. The histopathologic finding of polymorphonuclear leukocytes localized near the areas of corneal dissolution provides evidence for the role of polymorphonuclear leukocyte-derived collagenase as a contributing factor in the pathogenesis of sterile corneal ulceration in these patients.

Anterior segment ischemia in chronic herpes simplex keratouveitis.

Six patients with chronic herpes simplex keratouveitis developed a rapidly progressive ocular inflammation unresponsive to corticosteroid and antiviral therapy. Severe secondary glaucoma unresponsive to maximum medical therapy ensued and was treated by cyclocryotherapy in five patients. Ocular ischemia with secondary corneal and scleral calcification subsequently developed in all six patients. All had also received prolonged topical therapy with topical antiviral agents, corticosteroids, beta adrenergic blockers and epinephrine compounds. Three eyes eventually required enucleation for the relief of pain; one stabilized, and two others became phthisical. One of the phthisical eyes developed a secondary fungal endophthalmitis. Histopathologic examination of the three enucleated globes revealed extensive corneal, scleral and conjunctival calcification, secondary angle closure, iris and ciliary body necrosis, focal choroiditis, retinal necrosis and atrophy. The syndrome recognized in these patients appears to be a rare but devastating complication of herpes simplex keratouveitis, possibly exacerbated by the application of cyclocryotherapy and other factors.

Herpes simplex masquerade syndrome: acanthamoeba keratitis.

Acanthamoeba is a free-living, fresh-water protozoan that can cause severe corneal disease. Acanthamoeba keratitis can closely mimic epithelial and stromal Herpes simplex keratitis. Three cases of severe keratitis, were referred for treatment. One patient presented with a pseudodendritic epithelial lesion that gradually progressed to stromal involvement. A second patient presented with central stromal infiltrate and necrosis, while a third exhibited features of a disciform lesion with the later development of an immune ring. Acanthamoeba was recovered from the cornea in each case. The distinctive characteristics of the history and clinical findings in Acanthamoeba keratitis can aid the clinician in distinguishing between these two clinical entities. Cytopathology and special staining and culture techniques can confirm the diagnosis.