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Two dimensional (2D) nanosheets of MoS 2 were succesfully produced by an exfoliation process in aqueous media with the support from peptides and sonication. The exfoliation process assisted by uncapped MoSBP1 peptides was found to have enhanced efficiency in comparison to the capped counterpart. MoS 2 nanosheets obtained using uncapped MoSBP1 have thinner structures containing one layer of MoS 2 , while in capped version of peptides, MoS 2 nanosheets tend to form multilayer (up to 4) structures of exfoliated sheets. Molecular dynamics simulations indicate that inter-sheet gaps generated by sonication in MoS 2 nanostacks cannot be maintained by water only; the gaps closed after ∼11 ns. Both capped CMoSBP1 and uncapped MoSBP1 were seen to spontaneously insert into the gap in nanostacks of MoS 2 and they can ultimately maintain the inter-sheet gap for longer (≥20 ns). Potential of mean force profiles for the association of two MoS 2 nanosheets decorated with CMoSBP1 and MoSBP1 versions of peptides revealed that uncapped MoSBP1 peptides provide good protection from MoS 2 nanosheet re-unification. Such protection can prevent the nanosheets from reassociation and subsequent aggregation, whereas the capped CMoSBP1 peptides can offer protection, but over a shorter range. These simulation results could explain the experimental observation of greater efficiency of exfoliation in uncapped MoSBP1 peptides.

Background: Nosocomial infections are a worldwide healthcare issue, especially in intensive care units (ICUs), and they had a prevalence of 21.1% in 2023 in Spain. Numerous predisposing risk factors have been identified, with the most relevant being invasive techniques, including renal replacement therapies (RRTs). Several outstanding strategies have been published that prevent or reduce their incidence, including the nationwide ZERO in Spain, which consists of structured guidelines to be implemented to tackle this problem. One of these strategies, which is defined as 'highly recommended' in these projects, is selective digestive decontamination (SDD). The main aim of this study is to compare the incidences of ICU-acquired infections, including those due to multidrug-resistant bacteria (MDRB), in two cohorts of RRT with or without SDD. Methods: We conducted a multicenter, prospective, observational study at two tertiary hospitals in Spain. In total, 140 patients treated with RRT were recruited based on their exposure to SDD. Surveillance microbiological samples and nosocomial infection risk factors were obtained. Infection rates per 1000 days of exposure and the MDRB incidence density ratio were determined. Results: SDD statistically significantly reduced RRT-associated nosocomial infections (OR: 0.10, 95% CI: (0.04-0.26)) and the MDRB incidence density ratio (IDR: 0.156, 95% CI = 0.048-0.506). However, mechanical ventilation (OR: 7.91, 95% CI: (2.54-24.66)) and peripheral vascular disease (OR: 3.17, 95% CI: (1.33-7.56)) were significantly associated with increases in infections. Conclusions: Our results favor the use of SDD in ICU patients with renal failure undergoing CRRT as a tool for infection control.

The realization of multifunctional nanoparticle systems is essential to achieve highly efficient catalytic materials for specific applications; however, their production remains quite challenging. They are typically achieved through the incorporation of multiple inorganic components; however, incorporation of functionality could also be achieved at the organic ligand layer. In this work, we demonstrate the generation of multifunctional nanoparticle catalysts using peptide-based ligands for tandem catalytic functionality. To this end, chimeric peptides were designed that incorporated a Au binding sequence and a catalytic sequence that can drive ester hydrolysis. Using this chimera, Au nanoparticles were prepared, which sufficiently presented the catalytic domain of the peptide to drive tandem catalytic processes occurring at the peptide ligand layer and the Au nanoparticle surface. This work represents unique pathways to achieve multifunctionality from nanoparticle systems tuned by both the inorganic and bio/organic components, which could be highly important for applications beyond catalysis, including theranostics, sensing, and energy technologies.

Bovine polyomavirus-1 (BoPyV-1, Epsilonpolyomavirus bovis ) is widespread in cattle and has been detected in commercialized beef at supermarkets in the USA and Germany. BoPyV-1 has been questioned as a probable zoonotic agent with documented increase in seropositivity in people exposed to cattle. However, to date, BoPyV-1 has not been causally associated with pathology or disease in any animal species, including humans. Here we describe and illustrate pathological findings in an aborted bovine fetus naturally infected with BoPyV-1, providing evidence of its pathogenicity and probable abortigenic potential. Our results indicate that: (i) BoPyV-1 can cause severe kidney lesions in cattle, including tubulointerstitial nephritis with cytopathic changes and necrosis in tubular epithelial cells, tubular and interstitial inflammation, and interstitial fibroplasia; (ii) lesions are at least partly attributable to active viral replication in renal tubular epithelial cells, which have abundant intranuclear viral inclusions; (iii) BoPyV-1 large T (LT) antigen, resulting from early viral gene expression, can be detected in infected renal tubular epithelial cells using a monoclonal antibody raised against Simian Virus-40 polyomavirus LT antigen; and (iv) there is productive BoPyV-1 replication and virion assembly in the nuclei of renal tubular epithelial cells, as demonstrated by the ultrastructural observation of abundant arrays of viral particles with typical polyomavirus morphology. Altogether, these lesions resemble the "cytopathic-inflammatory pathology pattern" proposed in the pathogenesis of Human polyomavirus-1 -associated nephropathy in immunocompromised people and kidney allograft recipients. Additionally, we sequenced the complete genome of the BoPyV-1 infecting the fetus, which represents the first whole genome of a BoPyV-1 from the Southern Hemisphere. Lastly, the BoPyV-1 strain infecting this fetus was isolated, causing a cytopathic effect in Madin-Darby bovine kidney cells. We conclude that BoPyV-1 is pathogenic to the bovine fetus under natural circumstances. Further insights into the epidemiology, biology, clinical relevance, and zoonotic potential of BoPyV-1 are needed.

The non-destructive functionalisation of graphene in aqueous media is a critical process with the potential to enhance the versatility of the 2D nanosheet material as a technological enabler. This could also unlock strategies for a wider uptake of graphene in bio-related applications. Graphene functionalisation can be achieved using peptides that specifically recognise the carbon-based material, resulting in persistent non-covalent adsorption without damaging the nanosheet. Bio-conjugation of non-natural moieties with these peptides can incorporate multifunctionality, further extending the applicability of these interfaces. Here, bio-conjugates comprising a graphene-binding peptide with a fatty acid chain of varying length are investigated for their binding affinity and adsorbed structures at the aqueous graphene interface. Through an integration of quartz crystal microbalance and atomic force microscopy data with advanced sampling molecular simulations, variations in the binding of these bio-conjugates is determined. Conjugation at either terminus led to good interfacial contact, and for a given attachment point, the changes in the fatty acid length did not substantially disrupt the conformations of the adsorbed peptide domain. These findings provide a solid foundation for designing multi-functional bio-interfaces for sensing and healthcare.

Campylobacter fetusfetus (Cff) is a major infectious cause of abortion in sheep worldwide, and an opportunistic human pathogen. Information on Cff as an ovine abortifacient in South America is limited. We describe a case of abortion caused by a multidrug resistant strain of Cff in a sheep in Uruguay. In August 2017, 3/57 pregnant ewes (5.3%) aborted whithin one week. Histopathologic examination of the placenta of an aborted ewe revealed severe neutrophilic and fibrinonecrotizing placentitis with vasculitis and thrombosis of the chorionic arterioles. Cff was isolated on microaerobic culture in Skirrow agar, and further confirmed by 16S rDNA PCR amplification and sequencing, and endpoint and real time PCR assays. Antimicrobial sensitivity testing revealed resistance to tetracyclines, nalidixic acid, telithromycin and clindamycin. Other abortifacients were not detected. Further studies are necessary to determine the geographic distribution, ecology, epidemiology, economic impact, and antimicrobial resistance of Cff in sheep flocks in Uruguay., (Copyright © 2021 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Cohen syndrome (CS) is a rare syndromic form of rod-cone dystrophy. Recent case reports have suggested that cystoid maculopathy (CM) could affect CS patients with an early onset and high prevalence. Our study aims at improving our understanding and management of CM in CS patients through a retrospective case series of ten CS patients with identified pathogenic variants in VPS13B. Longitudinal optical coherence tomography (OCT) imaging was performed and treatment with carbonic anhydrase inhibitors (CAI) was provided to reduce the volume of cystoid spaces. CM affected eight out of ten patients in our cohort. The youngest patient showed a strong progression of macular cysts from the age of 4.5 to 5 years despite oral CAI medication. Other teenage and young adult patients showed stable macular cysts with and without treatment. One patient showed a moderate decrease of cystoid spaces in the absence of treatment at 22 years of age. Through a correlative analysis we found that the volume of cystoid spaces was positively correlated to the thickness of peripheral and macular photoreceptor-related layers. This study suggests that CAI treatments may not suffice to improve CM in CS patients, and that CM may resolve spontaneously during adulthood as photoreceptor dystrophy progresses., (© 2021. The Author(s).)

The evolution of Corporate Social Responsibility is forcing firms to adopt a new business approach based on combining competitiveness improvement with societal well-being. This evolution is materialized in the adoption of socially innovative practices to solve complex social problems, where collaboration is a key to confront them. And it is that, considering the existence of huge social and environmental challenges, independent actions undertaken by each of the societal actors with only their own resources reveal clearly insufficient to address them. Thus, a way firms can encourage the achievement of the Sustainable Development Goals (SDGs) is done by partnering with stakeholders, and particularly by developing the strategies of co-creation with non-profits. This study assesses the effects of business-non-profit value co-creation on both the organizational performance of the partners, and the social results linked to the SDGs. The methodology used to study the existence of these relationships is known as structural equations modeling (SEM) analysis. The results derived from a quantitative-based research with 205 Spanish non-profits show a positive effect of co-creation on indicators at the micro- (individuals), meso- (both the organizations), and macro-(society) levels. Furthermore, positive indicators at the micro- and macro-levels have a positive influence on the performance of the partners., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Díaz-Perdomo, Álvarez-González and Sanzo-Pérez.)

Objective: Latino patients are overrepresented among cases of coronavirus disease 2019 (COVID-19) and are at an increased risk of severe disease. Prevalence of COVID-19 in Latinos with rheumatic diseases is poorly reported. This study was undertaken to characterize COVID-19 clinical features and outcomes in Latino patients with rheumatic diseases., Methods: We conducted a retrospective study of Latino patients with rheumatic diseases from an existing observational cohort in the Washington, DC area. Patients seen between April 1, 2020 and October 15, 2020 were analyzed in this study. We reviewed demographic characteristics, body mass index (BMI), comorbidities, and use of immunomodulatory therapies. An exploratory classification and regression tree (CART) analysis along with logistic regression analyses were performed to identify risk factors for COVID-19 and rheumatic disease flare., Results: Of 178 Latino patients with rheumatic diseases, 32 (18%) were identified as having COVID-19, and the incidence rate of infection was found to be 3-fold higher than in the general Latino population. No patients required intensive care unit-level care. A CART analysis and multivariable logistic regression analysis identified a BMI of >30.35 as a risk factor for COVID-19 (odds ratio [OR] 3.37 [95% confidence interval (95% CI) 1.5-7.7]; P = 0.004). COVID-19 positivity was a risk factor for rheumatic disease flare (OR 4.57 [95% CI 1.2-17.4]; P = 0.02)., Conclusion: Our findings indicate that Latino patients with rheumatic diseases have a higher rate of COVID-19 compared with the general Latino population. Obesity is a risk factor for COVID-19, and COVID-19 is a risk factor for rheumatic disease flare. Latino patients with risk factors should be closely followed up, especially post-COVID-19 in anticipation of disease flare., (Published 2021. This article is a U.S.Government work and is in the public domain in the USA.)

Formation of autoantibodies to carbamylated proteins (anti-CarP) is considered detrimental in the prognosis of erosive rheumatoid arthritis (RA). The source of carbamylated antigens and the mechanisms by which anti-CarP antibodies promote bone erosion in RA remain unknown. Here, we find that neutrophil extracellular traps (NETs) externalize carbamylated proteins and that RA subjects develop autoantibodies against carbamylated NET (cNET) antigens that, in turn, correlate with levels of anti-CarP. Transgenic mice expressing the human RA shared epitope (HLADRB1* 04:01) immunized with cNETs develop antibodies to citrullinated and carbamylated proteins. Furthermore, anti-carbamylated histone antibodies correlate with radiographic bone erosion in RA subjects. Moreover, anti-carbamylated histone-immunoglobulin G immune complexes promote osteoclast differentiation and potentiate osteoclast-mediated matrix resorption. These results demonstrate that carbamylated proteins present in NETs enhance pathogenic immune responses and bone destruction, which may explain the association between anti-CarP and erosive arthritis in RA., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: Cyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing inflammatory response in the brain and periphery. To date, however, the development of PET radioligands for COX-2 has had limited success., Methods: The novel PET tracer [ 11 C]MC1 was used to examine COX-2 expression [1] in the brains of four rhesus macaques at baseline and after injection of the inflammogen lipopolysaccharide (LPS) into the right putamen, and [2] in the joints of two human participants with rheumatoid arthritis and two healthy individuals. In the primate study, two monkeys had one LPS injection, and two monkeys had a second injection 33 and 44 days, respectively, after the first LPS injection. As a comparator, COX-1 expression was measured using [ 11 C]PS13., Results: COX-2 binding, expressed as the ratio of specific to nondisplaceable uptake (BP ND ) of [ 11 C]MC1, increased on day 1 post-LPS injection; no such increase in COX-1 expression, measured using [ 11 C]PS13, was observed. The day after the second LPS injection, a brain lesion (~ 0.5 cm in diameter) with high COX-2 density and high BP ND (1.8) was observed. Postmortem brain analysis at the gene transcript or protein level confirmed in vivo PET results. An incidental finding in an unrelated monkey found a line of COX-2 positivity along an incision in skull muscle, demonstrating that [ 11 C]MC1 can localize inflammation peripheral to the brain. In patients with rheumatoid arthritis, [ 11 C]MC1 successfully imaged upregulated COX-2 in the arthritic hand and shoulder and apparently in the brain. Uptake was blocked by celecoxib, a COX-2 preferential inhibitor., Conclusions: Taken together, these results indicate that [ 11 C]MC1 can image and quantify COX-2 upregulation in both monkey brain after LPS-induced neuroinflammation and in human peripheral tissue with inflammation., Trial Registration: ClinicalTrials.gov NCT03912428. Registered April 11, 2019.

Bovine viral diarrhea virus (BVDV, Pestivirus) causes significant economic losses to the livestock industry worldwide. Although serological surveys show that BVDV exposure is widespread in cattle in Uruguay, BVDV-associated diseases are greatly underreported. The aim of this work is to describe the epidemiological, clinical, pathological, and virological findings from spontaneous outbreaks of BVDV-associated diseases in cattle in Uruguay. Diagnostic investigations were performed during 6 spontaneous disease outbreaks on beef and dairy cattle farms in the departments of Colonia, Rio Negro, and Soriano between November 2016 and April 2018. Carcasses of 8 naturally deceased cattle from these outbreaks were necropsied and subjected to histological examination and immunohistochemistry to detect BVDV antigen in the tissues. Reverse transcription real-time PCR and genomic sequencing were also performed to identify BVDV at the species and subtype levels. Other ancillary diagnostic tests, including bacterial cultures, were performed on a case-by-case basis to rule in/out differential diagnoses based on initial clinicopathological presumptive diagnoses. BVDV-associated conditions that were diagnosed in the 8 cases included mucosal disease, transient postnatal BVDV infections associated with digestive/septicemic salmonellosis by Salmonella serovar typhimurium, Histophilus somni bronchopneumonia, urinary tract coinfections with Escherichia coli and Streptococcus sp., enteric coinfection with coccidia, and transplacental fetal infections and abortions with Neospora caninum coinfection. BVDV-1a and BVDV-2b were each identified in four of the eight cases. We conclude that BVDV-1a and BVDV-2b contribute significantly to disease and mortality in cattle in Uruguay. Future research should estimate the economic impact of BVDV in the Uruguayan livestock sector.

Aim: Oculocutaneous albinism type 1 (OCA1) is due to TYR mutations. c.1205G>A/p.Arg402Gln (R402Q) is a thermosensitive variant of the TYR gene that has been reported to be responsible for mild forms of OCA1. The aim of our study was to define the phenotype associated with this variant., Methods: In our retrospective series, among 268 patients diagnosed with OCA1, 122 (45.5%) harboured one pathogenic variant of TYR , and the R402Q variant ensured to be in trans by segregation analysis in 69 patients (25.7%), constituting the 'R402Q-OCA1' group. 146 patients harboured two pathogenic variants of the TYR gene other than R402Q. Clinical records were available for 119 of them, constituting the 'Classical-OCA1' group., Results: Most R402Q-OCA1 patients presented with white or yellow-white hair at birth (71.43%), blond hair later (46.97%), a light phototype but with residual pigmentation (69.64%), and blue eyes (76.56%). Their pigmentation was significantly higher than in the classical-OCA1 group. All patients from the R402Q-OCA1 group presented with ocular features of albinism. However the prevalence of photophobia (78.13%) and iris transillumination (83.87%) and the severity scores of iris transillumination, retinal hypopigmentation and foveal hypoplasia were lower in the R402Q-OCA1 group. Visual acuity was higher in the R402Q-OCA1 group (0.38±0.21 logarithm of the minimum angle of resolution vs 0.76±0.24). Investigations concerning a possible additive effect of the c.575C>A/p.Ser192 (S192Y) variant of TYR in cis with R402Q, suggested by others, showed no significant impact on the phenotype., Conclusion: The R402Q variant leads to variable but generally mild forms of albinism whose less typical presentation may lead to underdiagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) [year]. Re-use permitted under CC BY. Published by BMJ.)

Bezoar is an accumulation of organic substances in the gastrointestinal tract; trichobezoar refers to the accumulation of hair usually in the stomach and even beyond it (Rapunzel syndrome). The incidence of this condition is extremely rare, 90 % of cases occur in women, and 80 % of these occur in those under 30 years of age and are related to anxiety behaviors and psychiatric disorders. The integral approach in these patients is fundamental, together with the interdisciplinary follow-up, treating the underlying psycho-emotional causes and adequate psychoeducation with the patients and their relatives, in order to reduce the risk of possible recurrences. We present the clinical case of a patient of school age, with a history of physical abuse by her stepfather and subsequent anxious behaviors (trichotillomania and trichophagia)., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

A fast, sensitive, and selective method for the simultaneous determination of one pair of synthetic colorants commonly found mixed in food products, Amaranth (AM) and Tartrazine (TZ), based on their adsorption and oxidation on a screen-printed electrode (SPE) is presented. The variation of peak current with pH, supporting electrolyte, adsorption time, and adsorption potential were optimized using square wave adsorptive voltammetry. The optimal conditions were found to be: pH 3.2 (PBS), E ads 0.00 V, and t ads 30 s. Under these conditions, the AM and TZ signals were observed at 0.56 and 0.74 V, respectively. A linear response were found over the 0.15 to 1.20 µmol L -1 and 0.15 to 0.80 µmol L -1 concentrations, with detection limits (3σ/slope) of 26 and 70 nmol L -1 for AM and TZ, respectively. Reproducibility for 17.7 µmol L -1 AM and TZ solutions were 2.5 and 3.0% ( n = 7), respectively, using three different electrodes. The method was validated by determining AM and TZ in spiked tap water and unflavored gelatin spiked with AM and TZ. Because a beverage containing both AM and TZ was not found, the method was applied to the determination of AM in a kola soft drink and TZ in an orange jelly and a soft drink powder., Competing Interests: The authors declare no conflict of interest.

Purpose: To describe a series of patients with Bardet-Biedl syndrome (BBS) and predominantly retinal cone dysfunction, a previously only rarely reported association., Design: Retrospective observational case series., Methods: Seven patients with clinically proven Bardet-Biedl syndrome had undergone detailed ocular phenotyping, which included fundus examination, Goldmann visual fields, fundus autofluorescence imaging (FAF), optical coherence tomography (OCT), and electroretinography (ERG). Mutational screening in the BBS genes was performed either by direct Sanger sequencing or targeted next-generation sequencing., Results: All 7 patients had proven BBS mutations; 1 had a cone dystrophy phenotype on ERG and 6 had a cone-rod pattern of dysfunction. Macular atrophy was present in all patients, usually with central hypofluorescence surrounded by a continuous hyperfluorescent ring on fundus autofluorescence imaging. OCT confirmed loss of outer retinal structure within the atrophic areas. No clear genotype-phenotype relationship was evident., Conclusions: Patients with Bardet-Biedl syndrome usually develop early-onset retinitis pigmentosa. In contrast, the patients described herein, with molecularly confirmed Bardet-Biedl syndrome, developed early cone dysfunction, including the first reported case of a cone dystrophy phenotype associated with the disorder. The findings significantly expand the phenotype associated with Bardet-Biedl syndrome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: MSX2 mutations are a very rare cause of craniosynostosis. Gain-of-function mutations may lead to the Boston-type craniosynostosis with limb defects and refraction errors, whereas loss-of-function mutations causes primary osseous defects such as enlarged parietal foramina., Materials and Methods: Herein we report the case of a child with bicoronal synostosis and cutaneous syndactylies, who presented iridal and chorioretinal colobomas. Due to the craniofacial features that were prominent in the clinical picture, the genes involved in craniosynostosis were explored., Results: The patient disclosed an intragenic duplication of the entire MSX2 gene whereas no mutation was identified in any major genes known to be involved in craniosynostosis., Conclusion: This is the first report of an eye development defect due to an increase in the MSX2 copy number in a human being. The implication of this gene in eye development has already been shown in several animal models. Indeed, overexpression of the Msx2 gene in a mouse model resulted also in optic nerve aplasia and microphthalmia. This report expands the phenotypic spectrum of the MSX2 mutations impacting early ocular development knowledge.

A topological-mathematical model has been arranged to search for new derivatives of deoxyuridine and related compounds acting as antimalarials against Plasmodium falciparum. By using linear discriminant and multilinear regression analysis a model with two functions was capable to predict adequately the IC(50) for each compound of the training and test series. After carrying out a virtual screening based upon such a model, new structures potentially active against P. falciparum are proposed.

Splenic injury in a newborn is a rare occurrence. It typically presents as an acute abdomen in an unstable patient. The authors present a case of splenic injury in a stable newborn infant with isolated scrotal findings. Workup included a testicular ultrasound scan with colorflow Doppler as well as abdominal and pelvic computerized tomography. The patient was treated nonoperatively with serial hematocrits and examinations and was discharged home after a brief hospital course.

Numerous immunochemical methods are now available for the detection of antibodies to gangliosides. An amplified ELISA method for detection of autoantibodies to NGcGM3 ganglioside in the sera of patients with various type of renal diseases was developed. IgM antibodies were found in 39 out of 53 sera of patients using 30 normal healthy blood donor as a negative control. For human IgG conjugate no reactivity to NGcGM3 was seen in the sera. Positive ELISA results were confirmed by TLC-immunostaining using GM3, NGcGM3, NGcGM2 and Standard bovine gangliosides (GM1, GD1a, GD1b and GT1b). All sera were also assayed for reactivity with GM3 in ELISA to determine the line specificity of these antibodies. Based on these results, a protocol for a sensitive and reproducible amplification ELISA system for serum anti-NGcGM3 antibodies in patients with renal or other diseases is presented. The ELISA method described here in appear to be useful adjunt to measure antiNGcGM3 antibodies in sera of patients with various type of renal or other diseases.

Serum levels of tumor necrosis factor alpha/cachectin (TNF alpha) were studied in a group of adult patients with sickle cell disease (SCD), which include 31 patients with homozygous SS hemoglobinopathy and 10 patients bearing double heterozygous SC hemoglobinopathy and in their matched normal controls. All patients tested did not show any form of crisis for at least 4 weeks prior to the extraction of the sample. The amount of TNF alpha in serum was quantitated by means of an immunoenzymatic assay with a lower limit of detection of 25 pg/ml. The percentage of sera with detectable levels of TNF alpha was significantly increased in SCD patients as compared with the normal controls. Mean TNF alpha values in individuals with detectable levels of the cytokine were also significantly higher in the whole group of SCD patients and in patients bearing either SS or SC hemoglobinopathies than in the control group. An inverse correlation was observed between the percentages of Hb F and the levels of TNF alpha found in the sera from the patients.

To study the capacity of peripheral blood mononuclear cells (PBMC) from patients with sickle cell disease to synthesize antibodies in vitro, the levels of IgM, IgG, and IgA were quantitated in supernatants of cultured PBMC from a group of asymptomatic adults with sickle cell disease and from normal controls. The rates of spontaneous synthesis of IgM were similar in nonstimulated cultures of PBMC from patients and controls, whereas the amounts of IgG and IgA produced spontaneously by nonstimulated lymphocytes from the patients were significantly greater than those from controls. Similar levels of IgM, IgG, and IgA were detected in the supernatants of cultures stimulated with pokeweed mitogen from patients and controls. Thus, the capacity of PBMC to respond in vitro to pokeweed mitogen was preserved in the patients. The enhanced spontaneous synthesis of IgG and IgA suggests the presence of chronic polyclonal activation of B cells and/or defective regulation of the production of antibodies.

Mitogen induced lymphoproliferative responses and lymphocyte sub-populations were studied in a group of sickle cell disease (SCD) patients with homozygous SS hemoglobinopathy. Even though the response to a sub-optimal dose of Con A (0.5 microgram/ml of culture) was significantly decreased in patients with SCD, the proliferative responses to optimal doses of Con A, to PHA and to PWM were preserved in the patients. Addition of indomethacin to the cultures increased to a more significant degree the response to Con A of lymphocytes from patients than from the normal controls. Study of the mononuclear cell subsets indicated that the relative and absolute numbers of B lymphocytes as well as those of monocytes were significantly increased in the patients' group. The percentage of T3+ lymphocytes was found decreased in SCD. However, a rise in the number of T11+ and T4+ lymphocytes as well as in the helper/suppressor cell ratio was observed in the patients as compared to controls.