Mitigation measures against Coronavirus Disease 2019 (COVID-19) in overnight faith-based camps: summer 2021.

OBJECTIVE: In this study, we describe community-based nonpharmaceutical interventions (NPIs) incorporated into COVID-19 mitigation protocols, and SARS-CoV-2 incidence at five faith-based summer camps in the US. STUDY DESIGN: Retrospective cohort study. METHODS: Six southeastern states within the United States (13 sites) were assessed from May 30 to August 14, 2021 (13 sites; N = 13,132; May-August 2021). Camp mitigation policies and NPIs (including masking, vaccinations, meal arrangements, physical distancing, pre-arrival testing, symptom screening, quarantine/isolation, and ventilation upgrades), and SARS-CoV-2 infections were tracked at each site. RESULTS: The symptomatic primary case attack rate was 24.7 (range: 0.0-120.0) cases per 100,000 people per week. Fewer infections were observed in camps with greater mitigation protocols. CONCLUSION: These findings suggest that nonpharmaceutical mitigation can promote stable access to youth programs for historically vaccine-hesitant subgroups. Policy recommendations for nonpharmaceutical interventions to prevent respiratory viral transmission in overnight youth faith-based camp settings may include outdoor activities, accessible symptomatic tests, prearrival testing, indoor mask use, small cohorts, physical distancing, and protocols to minimize staff exposures during time off.

Combined fused in sarcoma-positive (FUS+) basophilic inclusion body disease and atypical tauopathy presenting with an amyotrophic lateral sclerosis/motor neurone disease (ALS/MND)-plus phenotype.

AIMS: Amyotrophic lateral sclerosis/motor neurone disease (ALS/MND) is characterized by the presence of inclusions containing TDP-43 within motor neurones. In rare cases, ALS/MND may be associated with inclusions containing other proteins, such as fused in sarcoma (FUS), while motor system pathology may rarely be a feature of other neurodegenerative disorders. We here have investigated the association of FUS and tau pathology. METHODS: We report a case with an ALS/MND-plus clinical syndrome which pathologically demonstrated both FUS pathology and an atypical tauopathy. RESULTS: Clinical motor involvement was predominantly present in the upper motor neurone, and was accompanied by extrapyramidal features and sensory involvement, but with only minimal cognitive impairment. The presentation was sporadic and gene mutation screening was negative. Post mortem study demonstrated inclusions positive for FUS, including basophilic inclusion bodies. This was associated with 4R-tauopathy, largely as non-fibrillary diffuse phospho-tau in neurones, with granulovacuolar degeneration in a more restricted distribution. Double-staining revealed that neurones contained both types of protein pathology. CONCLUSION: FUS-positive basophilic inclusion body disease is a rare cause of ALS/MND, but in this case was associated with an unusual atypical tauopathy. The coexistence of two such rare neuropathologies raises the question of a pathogenic interaction.

Osteogenesis imperfecta: Ultrastructural and histological findings on examination of skin revealing novel insights into genotype-phenotype correlation.

Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. Over 90% of patients with OI have a mutation in COL1A1/COL1A2, which shows an autosomal dominant pattern of inheritance. In-depth phenotyping and in particular, studies involving manifestations in the skin connective tissue have not previously been undertaken in OI. The aims of the study were to perform histological and ultrastructural examination of skin biopsies in a cohort of patients with OI; to identify common and distinguishing features in order to inform genotype-phenotype correlation; and to identify common and distinguishing features between the different subtypes of OI. As part of the RUDY (Rare Diseases in Bone, Joints and/or Blood Vessels) study, in collaboration with the NIHR Rare Diseases Translational Research Collaboration, we undertook a national study of skin biopsies in patients with OI. We studied the manifestations in the skin connective tissue and undertook in-depth clinical and molecular phenotyping of 16 patients with OI. We recruited 16 patients: analyses have shown that in type 1 collagen mutation positive patients (COL1A1/ COL1A2) (n-4/16) consistent findings included: variable collagen fibril diameter (CFD) and presence of collagen flowers. Histological examination in these patients showed an increase in elastic fibers that are frequently fragmented and clumped. These observations provide evidence that collagen flowers and CFD variability are consistent features in OI due to type 1 collagen defects and reinforce the need for accurate phenotyping in conjunction with genomic analyses.

Ocular surface foreign bodies: novel findings mimicking ocular malignant melanoma.

PURPOSE: Malignant melanoma of the eye is an uncommon condition that is important to recognise. We describe three cases in which ocular foreign bodies have masqueraded as ocular malignant melanoma. METHODS: Interventional case reports. RESULTS: Case 1 describes diathermy-induced carbon particle implantation, during plaque therapy for the treatment of uveal melanoma, mimicking recurrence with extra-scleral invasion. Case 2 shows a foreign body called 'mullite' mimicking conjunctival melanoma. Case 3 demonstrates a conjunctival foreign body called 'illite' that mimicked a limbal melanocytic lesion, clinically thought to be either melanocytoma or melanoma. CONCLUSION: This report highlights the importance of careful history taking, examination, and appropriate biopsy in cases of suspected malignant melanoma, to prevent unnecessary and potentially radical treatment.

Small round cell tumor with biphenotypic differentiation and variant of t(21;22)(q22;q12).

A 14-year-old boy presented with a soft tissue swelling on the outer aspect of his left upper arm. Examination of the tumor by light microscopy showed a small round cell tumor with a rare focus of myogenic differentiation. Myogenic differentiation was confirmed on ultrastructural examination by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Conventional G-banding and fluorescent in situ hybridization (FISH) demonstrated a complex variant of t(21;22)(q22;q12). By RT-PCR, the EWS-ERG fusion transcript was defined as type 9e. This tumor was unusual in that it showed characteristics of myogenic and neural differentiation, and contained a rearrangement of the EWS gene consistent with a diagnosis of Ewing's sarcoma. This supports the hypothesis that a class of biphenotypic childhood sarcomas, with features of myogenic and neural differentiation, exists that may be related to the Ewing's sarcoma family of tumors.

Electron microscopy of myocardial tissue. A nine year review.

AIM: To review and reassess the role of this department's experience with routine electron microscopy of myocardial tissues. METHODS: A nine year series of myocardial samples that underwent electron microscopy analysis were audited. Fifty nine samples were derived from 46 male and 13 female subjects with an age range of 15-90 years (mean, 50.6). Forty two samples were endomyocardial specimens, with 13 being derived from explanted hearts, and four from necropsies. Two cases were from transplanted hearts. These were all reviewed in a blinded fashion, by all three authors separately, in terms of the myocardium at the ultrastructural level. Subsequently, the interpretations/diagnoses were cross compared with the light microscopy and clinical data results. [figure: see text] RESULTS: Four cases of amyloid were identified; in addition, one case of granulomatous inflammation and one case of basophilic degeneration were seen, although all these had been evident on light microscopy. One case of possible mitochondrial myopathy was found. A total of 18 cases revealed changes of a presumed non-specific type including glycogen, lipid, and mitochondrial accumulations. Varying types of degeneration involving myofibres were seen together with variations in interstitial fibrosis and occasional cytoplasmic inclusions. CONCLUSION: Overall, although interesting, the electron microscopy of myocardial tissue added little to the understanding of the patient's disease, with only one case showing changes not found at light microscopy or with other investigations. Further study might shed light on the "non-specific" ultrastructural findings encountered.

Differential effects of CD18, CD29, and CD49 integrin subunit inhibition on neutrophil migration in pulmonary inflammation.

Neutrophil migration to lung alveoli is a characteristic of lung diseases and is thought to occur primarily via capillaries rather than postcapillary venules. The role of adhesion molecules CD18 and CD29 on this migration in a mouse model of lung inflammation has been investigated. The number of neutrophils present in bronchoalveolar lavage fluid was determined 4 h after intratracheal instillation of LPS (0.1-1 microg) or murine recombinant KC (CXC chemokine, 0.03-0.3 microg). Both stimuli produced a dose-related increase in neutrophil accumulation. Intravenous anti-mouse CD18 mAb, 2E6 (0.5 mg/mouse), significantly (p < 0.001) attenuated LPS (0.3 microg)- but not KC (0.3 microg)-induced neutrophil accumulation. The anti-mouse CD29 mAb, HM beta 1-1 (0.02 mg/mouse), significantly (p < 0.05) inhibited both LPS (0.3 microg)- and KC (0.3 microg)-induced neutrophil migration. A second mAb to CD18 (GAME-46) and both F(ab')(2) and Fab of HM beta 1-1 produced similar results to those above, while coadministration of mAbs did not result in greater inhibition. Electron microscopy studies showed that CD29 was involved in the movement of neutrophils from the interstitium into alveoli. The effect of mAbs to CD49 (alpha integrin) subunits of CD29 was also examined. mAbs to CD49e and CD49f inhibited both responses, while anti-CD49b and CD49d significantly inhibited responses to KC only. These data suggest that CD29 plays a critical role in neutrophil migration in pulmonary inflammation and that CD49b and CD49d mediate CD18-independent neutrophil accumulation.

Cellular apoptosis and proliferation in experimental renal fibrosis.

BACKGROUND: The progression of chronic renal failure (CRF) is associated with the progressive deletion of renal cells along with the fibrosis of the kidney. We have studied the role of programmed cell death (apoptosis) in the progression of experimental CRF and renal scarring. METHODS: The sub-total (5/6th) nephrectomy (SNx) model of CRF was studied in adult male Wistar rats, with renal tissue collected from experimental and control animals on days 7, 15, 30, 60, 90, and 120 post SNx (n = 6 per group). These were examined for morphological signs of apoptosis by light and electron microscopy. Further, we stained the nuclear chromatin by the acridine orange fluorescent method and detected signs of DNA cleavage by endonucleases via the principal of TUNEL staining (ApopTag). Rates of cellular proliferation were measured simultaneously by immunohistochemical staining for the proliferating cell nuclear antigen (PCNA). In addition, cell division was monitored by counting of morphologically mitotic motifs detectable by light microscopy. RESULTS: Progressive renal insufficiency associated with glomerulosclerosis and tubulointerstitial fibrosis took place in the majority of SNx rats. In these animals, we noted a marked and progressive increase in the number of apoptotic glomerular, tubular as well as interstitial cells. The most significant apoptotic changes were seen in the tubules of remnant kidneys peaking at day 120 post-SNx. At this stage, the increase in apoptosis compared to controls was 10.33+/-2.67 (M+/-SEM) fold for glomerular cells (P< or =0.006), 26.20+/-4.56 fold for tubular cells (P < 0.0001) and 4.66+/-0.81 fold for interstitial cells (P< or =0.001). Parallel changes in the number of PCNA positive renal cells were observed. Maximal PCNA staining was seen at day 120 when the increase with respect to controls was 14.00+/-4.93 fold (P< or = 0.05) for glomerular cells, 60.01+/-12.20 fold (P< or =0.05) for tubular cells and 28.59+/-4.45 fold (P< or = 0.05) for interstitial cells. As expected, the number of cells undergoing division and detectable by conventional light microscopy was lower at any time point to those expressing PCNA. We also observed a close correlation between the severity of tubular atrophy and tubulointerstitial fibrosis with the rate of tubular apoptosis (r=0.970, R2 =0.941, P< or =0.001). CONCLUSIONS: We have shown a time-dependent increase in apoptosis and PCNA antigen positive staining in the sub-total nephrectomy model of chronic renal failure correlating with the progression of renal fibrosis. PCNA staining did not match analysis for mitosis and was considered to overestimate the number of proliferating cells in the tissue. With this reservation in mind and taking into account the relative time-frames in vivo of apoptosis and proliferation; apoptosis potentially outweighs proliferation by a factor of 2 8-fold, when examined over the same time period. Consequently, even small changes in the finite numbers of apoptotic cells become highly significant. Our results have shown the definite role of apoptosis within progression of renal damage and highlighted how it may contribute to the progression of tubular atrophy and play a role in the pathogenesis of tubulo-interstitial scarring.

Plexosarcoma of the bladder.

Plexosarcomas are rare soft tissue sarcomas, previously reported in association with gastrointestinal autonomic nerve (GAN) plexi. We report the first case arising from the autonomic nerve plexus of the bladder.

Disposition of didanosine in HIV-seropositive patients with normal renal function or chronic renal failure: influence of hemodialysis and continuous ambulatory peritoneal dialysis.

OBJECTIVE: To evaluate the pharmacokinetics of didanosine in patients with normal kidney function or chronic kidney failure. METHODS: Three groups of patients with human immunodeficiency virus (HIV) infection were studied: group I, six men with normal kidney function (creatinine clearance > 90 ml/min/1.73 m2); group II, six men with chronic renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD); and group III, four men and two women with chronic renal failure receiving hemodialysis three times a week. A 300 mg dose of didanosine was administered orally and intravenously according to a two-period randomized crossover design. Patients in group III were studied between hemodialysis sessions during the crossover periods. In addition, patients in group III were studied in a third period after administration of a 300 mg oral dose of didanosine 4 hours before hemodialysis. RESULTS: After intravenous administration in group I, the mean (+/-SD) total clearance (CLT) was 13.0 +/- 1.6 ml/min/kg and the elimination half-life (t 1/2) was 1.56 +/- 0.43 hour. In groups II and III, the CLT decreased significantly to 3.4 +/- 1.2 and 3.2 +/- 1.2 ml/min/kg, respectively, whereas the t1/2 increased to 3.60 +/- 0.82 hours and 3.11 +/- 0.88 hours, respectively. The absolute bioavailability of didanosine in groups I, II, and III was 42% +/- 12%, 52% +/- 6%, and 38% +/- 11%, respectively, and did not differ significantly. CAPD had little effect on the removal of didanosine, whereas approximately 30% of the drug present in the body at the start of dialysis was eliminated by an average 3-hour dialysis session. CONCLUSION: The clearance of didanosine is impaired in patients with chronic renal failure. To compensate, the dose and schedule of administration should be adjusted. It is recommended that one-fourth of the total daily dose of didanosine be administered once a day in this patient population.

Isolation of circulating megakaryocytes in man.

Recovery of the small numbers of megakaryocytes (MKs) known to be present in normal blood is difficult because of their low frequency. Isolation of circulating MKs was achieved using a modified filtration system in which untreated blood was passed through 5 microns polycarbonate membranes. MKs were retained while most other blood cells passed through the membranes. Four groups of MKs were identified in May Grünwald-Giemsa stained filters of blood from peripheral, central and umbilical veins and umbilical arteries. Type 1 MKs were nuclei with no visible cytoplasm. Types 2, 3 and 4 were nuclei with increasing amounts of cytoplasm. Type 4 MKs, possessing copious cytoplasm, were rarely isolated from peripheral venous blood but were more regularly encountered in central venous and cord blood. Filtration of whole blood through polycarbonate membranes is a useful technique for the isolation of circulating MKs, which are a normal physiological occurrence. Their presence is consistent with the production of platelets in the placenta during intra-uterine life, and subsequently in the pulmonary circulation.

Relative usefulness of electron microscopy and immunocytochemistry in tumour diagnosis: 10 years of retrospective analysis.

AIMS: To determine retrospectively the relative usefulness of electron microscopy and immunocytochemistry for tumour diagnosis; to monitor the influence of new antibodies and antisera on the use of these techniques in one laboratory. METHODS: During 1980 to 1989 inclusive, 726 tumours were examined by electron microscopy, 862 by immunocytochemistry, and 286 by both techniques. The choice of techniques and, for immunocytochemistry, the range of antibodies used were compared between each category of final diagnosis. RESULTS: During the study period there was a sharp fall in the use of electron microscopy and a corresponding rise in immunocytochemistry. These trends applied to all categories of final tumour diagnosis, but the use of electron microscopy was sustained longer for lesions suspected or eventually confirmed to be melanomas or amine precursor uptake decarboxylation cell carcinoma (APUDomas)--for example, carcinoid tumours. The immunocytochemistry:electron microscopy use ratios ranged from 2.07:1 to 0.44:1 for the categories in which lymphoma and APUDoma, respectively, were the final diagnoses. The abandonment of electron microscopy for suspected or confirmed lymphomas and carcinomas corresponded to the increasing availability of relevant antisera and antibodies. CONCLUSIONS: The wider application of immunocytochemistry for tumour diagnosis is endorsed, but electron microscopy should be retained for selected cases in which the results of immunocytochemistry might be predictably ambiguous or otherwise unhelpful.