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In October, twenty disabled artists were announced as the first class of Disability Futures Fellows and received grants of $50,000 each, to be used in whatever way is most useful [...]

Study Question: Does the immune response to coronavirus disease 2019 (COVID-19) infection or the BNT162b2 mRNA vaccine involve the ovarian follicle, and does it affect its function?Summary Answer: We were able to demonstrate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG in follicular fluid (FF) from both infected and vaccinated IVF patients, with no evidence for compromised follicular function.What Is Known Already: No research data are available yet.Study Design, Size, Duration: This is a cohort study, composed of 32 consecutive IVF patients, either infected with COVID-19, vaccinated or non-exposed, conducted between 1 February and 10 March 2021 in a single university hospital-based IVF clinic.Participants/materials, Setting, Methods: A consecutive sample of female consenting patients undergoing oocyte retrieval was recruited and assigned to one of the three study groups: recovering from confirmed COVID-19 (n = 9); vaccinated (n = 9); and uninfected, non-vaccinated controls (n = 14). Serum and FF samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and heparan sulfate proteoglycan 2 concentration, as well as the number and maturity of aspirated oocytes and day of trigger estrogen and progesterone measurements. Main outcome measures were follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers.Main Results and the Role Of Chance: Both COVID-19 and the vaccine elicited anti-COVID IgG antibodies that were detected in the FF at levels proportional to the IgG serum concentration. No differences between the three groups were detected in any of the surrogate parameters for ovarian follicle quality.Limitations, Reasons For Caution: This is a small study, comprising a mixed fertile and infertile population, and its conclusions should be supported and validated by larger studies.Wider Implications Of the Findings: This is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function and these early findings suggest no measurable detrimental effect on function of the ovarian follicle.Study Funding/competing Interest(s): The study was funded out of an internal budget. There are no conflicts of interest for any of the authors.Trial Registration Number: CinicalTrials.gov registry number NCT04822012. [ABSTRACT FROM AUTHOR]

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a systemic arterial disease characterized by impairment of vascular smooth muscle cell structure and function related to NOTCH3 mutations. Pathological findings include pathognomonic granular osmiophilic material (GOM) deposition with nonspecific hyalinization within the artery wall in a variety of tissues. The main clinical presentation is iterative strokes in young adults despite the lack of cardiovascular risk factors, leading to early dementia. Although arteriosclerosis and GOM have been found in kidneys from patients with CADASIL, kidney disease has been described only once up to now, in association with immunoglobulin A nephropathy. We report the case of a 61-year-old patient with a medical history of CADASIL and recent mild hypertension. His mother also showed neuropsychiatric symptoms and end-stage renal disease of unknown cause. The patient had a chronic kidney disease defined by means of estimated glomerular filtration rate using the 4-variable Modification of Diet in Renal Disease Study equation of 58 mL/min/1.73 m(2) associated with mild proteinuria and intermittent microscopic hematuria. Renal histological analysis showed severe arteriosclerosis and mild interstitial fibrosis. Glomeruli did not show mesangial immunoglobulin A deposition or focal segmental proliferation. Electron microscopic analysis showed typical GOM deposition in the vicinity of altered vascular smooth muscle cells in interlobular and juxtaglomerular arteries. The nephroangiosclerosis-like lesions were unusually severe in contrast to the recent mild hypertension. The presence of GOM strongly suggests that renal lesions were related to the NOTCH3 mutation. Here, we describe the first case of familial occurrence of kidney disease with decreased kidney function in the absence of coexisting nephropathy in patients with CADASIL. We discuss the role of NOTCH3 mutation in the pathogenesis of nephroangiosclerosis through functional impairment of renal microcirculation or primary Notch3-related vascular disease. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine in systemic lupus erythematosus (SLE) the prevalence and clinical significance of anticalpastatin antibodies (ACAST), an autoantibody population previously detected in sera from patients with various connective tissue diseases. Eighty-four patients with SLE (mean age: 30 years at diagnosis, females 77) that fulfilled ACR criteria were included in the study retrospectively. Several clinical and biological data were collected. ACAST were detected by a solidphase enzyme linked immunosorbent assay (ELISA) using as antigen a synthetic peptide corresponding to the 27 C-terminal amino acids of calpastatin (CAST-C27). The prevalence of ACAST-C27 was 13% (11/84) in SLE patients. No correlation was found between the presence of ACAST-C27 and clinical manifestations such as thrombosis and vasculitis. Furthermore, no correlation was observed with the presence of antiphospholipid antibodies (APL). However, we found a statistically significant association between the presence of ACAST-C27 and that of secondary Sjögren syndrome (P =; 0.01). The conclusion is ACAST-C27 are not associated with thrombosis in SLE patients. The association observed between ACAST-C27 and secondary Sjögren syndrome suggests that ACAST-C27 might be useful in discriminating a clinical subgroup of SLE patients. [ABSTRACT FROM AUTHOR]

Morgan R Godin, Preeya K Gupta Department of Ophthalmology, Division of Cornea and Refractive Surgery, Duke University Eye Center, Durham, NC, USA Abstract: A new topical ophthalmic medication, lifitegrast 5%, was recently approved by the US Food and Drug Administration for use in dry eye patients. Lifitegrast is an integrin antagonist that decreases inflammation on the ocular surface, thereby improving dry eye disease (DED). Through a series of prospective, multicenter, randomized, masked, placebo-controlled studies in >2,000 patients total, lifitegrast was shown to be effective for improvement in both the signs and symptoms of DED. A subsequent study focused on the safety profile of lifitegrast and demonstrated that the majority of adverse events were mild and resolved over time. Lifitegrast is now available for use in clinical practice. Keywords: OPUS-1, OPUS-2, OPUS-3, SONATA, LFA-1, ICAM-1, OSDI, ocular surface

* Cognitive processing and meaning theories suggest that a patient's psychological adjustment following a traumatizing event depends on an ability to cognitively integrate the trauma event and restore a sense of meaning in life. These processes may be facilitated by using coping strategies such as sharing concerns, mobilizing support, and reframing.* A correlational study explored the magnitude of the relationships between psychological adjustment, cognitive processing, sense of meaning, and coping strategies in critically injured patients 3 months after a potentially life-threatening injury.* Fifty-one critically injured patients completed the Brief Symptom Inventory, Bradburn's Psychological Well-Being Scale, Impact of Events Scale, the Meaning-of-Illness Questionnaire, and Family Crisis-Oriented Personal Evaluation Scale in face-to-face interviews 8-12 weeks after the accident. Bivariate and partial correlation coefficients were used to test the main hypothesis, and Pearson correlation coefficients, to address the three research questions.* The main hypothesis that psychological adjustment will be significantly related to cognitive processing, sense of meaning, and use of coping strategies in critically injured patients 3 months after the accident was partially upheld.* Depressive symptomatology was found to be significantly associated with increased cognitive processing efforts and a decreased ability to acknowledge the accident's negative effects on the self.* In contrast, psychological well-being was found to be significantly associated with decreased cognitive processing efforts and an increased ability to acknowledge the accident's negative effects on the self.* Restoring a sense of meaning, however, was found to be unrelated to sharing concerns, mobilizing support and re-framing. The potential theoretical and clinical implications of the findings for nursing practice are discussed. [ABSTRACT FROM AUTHOR]

Experience gained in a qualitative research-training project led a group of clinical nurse specialists to discover the value of using research interview strategies in their clinical work. Clinical interviews, designed to garner data sufficient to decide on interventions, narrow the focus of the interviewer to information deemed relevant to that end. Research interview strategies involve a temporary suspension of the search for intervention, encourage a full description of the respondent's story and experience, and emphasise really listening to that story. In this case it is the respondent who decides what the story is and what information is relevant. This leads the interviewer to a fuller understanding of the context and perceptions of the respondent. The understanding and knowledge thus obtained comprise a better foundation for devising interventions which are individualised and specific to the individual and family. [ABSTRACT FROM AUTHOR]

BACKGROUND: An altered arterial nitric oxide (NO) pathway could partly explain the damage to arteries observed in haemodialyzed (HD) patients. The present study was designed to non-invasively evaluate the NO pathway of peripheral conduit arteries in HD patients. METHODS: Twelve normotensive, non-diabetic HD patients treated with erythropoietin and 12 matched healthy controls (C) were included in the study. The effect of endogenous release of NO was assessed by measuring the flow-dependent vasodilatation of the radial artery (post-ischaemic hyperaemia), and the response to exogenous NO assessed using sublingual glyceryl trinitrate administration (GTN). RESULTS: Radial artery diameter (echo-tracking), radial blood flow (RBF: Doppler) and mean arterial pressure (Finapres) were identical at baseline in HD patients and in healthy subjects. The flow-dependent vasodilatation of the radial artery was decreased in HD patients (C: 9 +/- 1% vs HD: 3 +/- 05%, P < 0.05). The decrease in radial vascular resistance (C: -44 +/- 4% vs HD: -24 +/- 2%, P < 0.05) and the increase in radial diameter (C: 31 +/- 2% vs HD: 25 +/- 2%, P < 0.05) after GTN administration were less in HD patients than in controls. The ratio between the increase in diameter after hyperaemia to the increase in diameter after GTN, was also diminished in HD patients (C: 30 +/- 3% vs HD: 13 +/- 2%, P < 0.001). CONCLUSIONS: The flow-dependent vasodilatation of peripheral conduit arteries is altered in HD patients and is associated with a slight but significant decrease in the vasodilating response to exogenous NO. These results suggest, in the absence of changes in basal radial vascular resistance and arterial diameter, more a decrease in endothelial NO bioavailability, than an increase in basal vascular tone. [ABSTRACT FROM PUBLISHER]

To assess the potential benefit of druginduced renal haemodynamic changes in patients with chronic renal failure, we have evaluated the effects of the β-blocking agent tertatolol on blood pressure, glomerular filtration rate, and renal plasma flow. Inulin and PAH clearances were performed before and after 3 months treatment and oral tertatolol, 5 mg daily in eight hypertensive patients with moderate chronic renal failure.After 3 months of treatment, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) increased significantly by 10% and 13% respectively, whereas renal vascular resistance decreased by 16% and the filtration fraction was unchanged.These results indicate that tertatolol possesses novel renal haemodynamic properties in hypertensive patients with chronic renal failure. However, the longterm benefit of such a therapy is yet to be confirmed. [ABSTRACT FROM PUBLISHER]

Six cases of chronic renal failure related to granulomatous renal sarcoidosis are reported and compared with data in the literature.The particular features of sarcoidosis granulomatous interstitial nephritis should be emphasised because presentation may be misleading. Renal failure usually presents with a rapidly progressive course, either isolated or associated with mild proteinuria and sterile leukocyturia, while extrarenal localisations may be absent.Diagnosis should be suspected on the basis of elevated or paradoxically normal serum calcium concentrations, due to increased plasma concentrations of calcitriol, while immunoreactive circulating parathormone concentrations are depressed. Calcitriol as well as angiotensinconverting enzyme could represent unregulated secretion products from granulomatous tissue and their plasma concentrations may roughly reflect activity of the disease.Early corticosteroid treatment dramatically improves renal function but long-term renal prognosis may be oblitered due to progressive chronic renal failure related to fibrosis scarring. [ABSTRACT FROM PUBLISHER]

Functional, histological and biochemical changes of the renal cortex were studied after treatment of Wistar female rats with 400 mg/kg cefoxitin for eight days. This treatment was composed with those of cephaloridine, cefazolin or cephalothin and with increasing dosages of gentamicin for eight days. Blood creatinine rose after administration of 50 and 100 mg/kg gentamicin and of 400 mg/kg cephaloridine. Pathological investigation showed slight renal lesions in the groups receiving 400 mg/kg cefoxitin while 50 mg/kg gentamicin induced acute tubular necrosis. Lysosomal enzyme structural latency was not affected by cephalosporins or the cefamycin and the changes in enzymic activities of the renal cortex were less severe after treatment with cefoxitin or cephalosporins than after gentamicin. Cefoxitin did not induce any detectable nephrotoxicity and the study of the cefoxitin and gentamicin combination showed a decrease of the gentamicin toxicity in the pathological investigation and the study of renal function. Thus in our model, cefoxitin may be combined with gentamicin treatment without risk of nephrotoxic potentialization. [ABSTRACT FROM PUBLISHER]

The pharmacokinetics of cefotaxime was investigated in 6 healthy subjects and in 22 uraemic patients with various degrees of renal insufficiency.After i.v. bolus injection of a single 15 mg/kg dose, pharmacokinetic data were calculated using a three-compartment open body model.In healthy subjects, after i.v. injection, the mean terminal serum half-life T½ β was 1.44 ± 0.45 h and apparent volume of distribution Vdarea was 34.23 ± 9.19 1/1.73 m2. After a similar i.m. dose, the mean peak serum level was 25.32 ± 3.94 mg/l, the elimination T½ was 1.07 ± 0.14 h and bioavailability was 91.5±14.8 %.Fifty to sixty per cent of the injected dose was recovered unchanged in 24 h urines. Renal and serum clearances were 170 and 280 ml/min/1.73 m2, respectively.In uraemic patients, after a single 15 mg kg i.v. dose, T½ β increased in relation to degree of renal impairment up to 10.81 ± 3.23 h in patients with creatinine clearance (Ccr) lower than 8 ml/min/1.73 m2.In haemodialysis patients, T½ β was out of dialysis 8.96 ± 6.47 h and on a 4 to 6 h-dialysis session 1.98 ± 0.72 h. 62.3 ± 17.4 % of the drug was extracted by dialysis.The apparent volume of distribution was not significantly modified by renal insufficiency. Relationships between pharmacokinetic data (T½ β,) and biological parameters of renal function (serum creatinine, Ccr) provide a basis for dosage adjustment in renal failure. [ABSTRACT FROM PUBLISHER]

Pharmacokinetics data of cefoxitin sodium were determined in normal subjects and in uraemic patients. All subjects (5 normal and 20 uraemic) received 30 mg/kg of cefoxitin i.v. in 30-min. infusions. In healthy subjects, the serum half-life (T½) was 0.78 ±0.10 h, and the apparent volume of distribution (A.V.D.) was 7.70 1. The mean renal clearance was 329 ml/min/1.73 m2.For uremic patients we observed a very sharp increase in T½ when creatinine clearance fell below 30 ml/min compared to 0.78 h in normal subjects, T½ was 21.56 h in patients with very poor renal function. During a haemodialysis session the serum levels decreased: 86.3% of the initial serum concentration was extracted. [ABSTRACT FROM PUBLISHER]

The pharmacokinetics of a single oral 200 mg dose of netivudine (1-(β-D-arabino-furanosyl)-5-(1-propynyl)uracil), a nucleoside analogue under development for use in varicella zoster virus infections, were studied in 12 renal failure (RF) subjects (creatinine clearance 15±7mL/min) and 12 age-matched healthy subjects with normal creatinine clearance. Blood and urine samples were collected up to nine days after drug administration. Concentrations of netivudine and of its main metabolite, the pyrimidine base 5-(1-propynyl)uracil (5 PU), were determined by a specific high performance liquid chromatography assay. The mean peak plasma concentrations of netivudine, Tmax and volume of distribution were not significantly affected by RF. The elimination half-life of netivudine was approximately 15 h in subjects with normal renal function and 60 h in RF patients. Plasma and renal clearances of netivudine were significantly reduced in RF patients and AUC was three to four times higher in these patients. Cmax and AUC of 5 PU were higher in RF patients, and the half-life was also significantly longer. However, the half-life of this metabolite was much lower than that of the parent compound. Tmax and the lag time were similar in the two groups. There were highly significant correlations for netivudine and 5 PU between half-life and creatinine clearance and between renal clearance and creatinine clearance. These findings suggest that netivudine dosage may need to be reduced in patients with severe renal failure, and confirm that formation of the 5 PU is independent of the elimination of netivudine from plasma. [ABSTRACT FROM PUBLISHER]

The pharmacokinetics of temocillin were investigated in five normal subjects and in 20 uraemic patients. Normal subjects were given single intravenous doses of 3.75, 7.5 and 15 mg/kg of temocillin and a single intramuscular dose of 7.5 mg/kg. Patients with renal impairment were given 7.5 mg/kg of the antibiotic intravenously. A three-compartment open model was used to calculate kinetic data after iv administration. Pharmacokinetic parameters of temocillin were similar both for the three iv doses and for the im dose. The terminal serum half-lives (T) averaged 4.75–5.88 h. The central distribution volume () and the apparent volume of distribution () were 0.093–0.111 and 0.268–0.303 1/kg, respectively. Renal and total body clearances were within 27.4–34.1 and 40.2–47.8 ml/min/1.73 m2, respectively. 67.471.5% of the dose was recovered unchanged in urine over 24 h. Intramuscular dosing of 7.5 mg/kg gave a mean peak level of 26.71 mg/1 at 1.67 h. In uraemic patients, similar maximum serum concentrations were found after a single 7.5 mg/kg iv dose. The terminal half-life increased according to the degree of renal failure, from 5 h in normal subjects to about 30 h in severe uraemic patients. Renal impairment did not significantly modify Vdarca, fractional clearance (C/GFR) and non renal clearance. 65.2% of the antibiotic was removed during haemodialysis. Dosage adjustments of temocillin in uraemic patients are proposed. [ABSTRACT FROM PUBLISHER]

The pharmacokinetics of cefadroxil were studied in patients with different degrees of renal impairment after a single oral dose of 1000 mg. The standard open one-compartment model was used to determine the pharmacokinetic data. In normal subjects, the mean peak level was 25·72 mg/l and occurred at 1·20 h. The elimination half-life averaged 1·39 ± 0·06 h and 93% of the dose was recovered in 24 h urines. Renal clearance (167 ml/min/1 73 m2 exceeded creatinine clearance. In uraemic patients the peak serum levels were higher (20–60 mg/l) and occurred later (2 to 6 h). The elimination half-life increased in relation to the degree of renal failure moderately where the creatine clearance was 25 to 50 ml/l min/1·73 m2 reaching 25 h in haemodialysis patients. The apparent volume of distribution was not significantly modified in renal impairment (≃20·1). Haemodialysis increases the elimination of cefadroxil, the elimination half-life during dialysis being 3·37 ± 0·53 h. The elimination rate constant (Kel) correlated well with renal function. The dosage regimen of cefadroxil should be adjusted according to the severity of renal failure. [ABSTRACT FROM PUBLISHER]

1. The pharmacokinetics of a single 1 mg dose of cilazapril were determined in six subjects with normal renal function and in 19 uraemic patients with various degrees of renal impairment. 2. Significant decreases in systolic and diastolic blood pressure were noted in all groups of subjects between 2 and 8 h after administration of 1 mg cilazapril. 3. There was a significant correlation between ACE inhibition at 24 h and creatinine clearance (CrCL). 4. For cilazapril, Cmax and tmax were independent of creatinine clearance. AUC(24) was inversely related to CrCL and apparent plasma clearance (CL/F) was directly related to CrCL. 5. For cilazaprilat, Cmax and tmax were related to creatinine clearance. AUC(24) was inversely related to CrCl and apparent plasma clearance (CL/F) was directly related to CrCL. 6. Dialysis clearance was approximately 2 l h-1 for cilazapril and for cilazaprilat. 7. The effects of renal impairment on cilazapril and cilazaprilat kinetics were similar to those observed for other inhibitors of angiotensin-converting enzyme such as captopril, enalapril and lisinopril. 8. It may be necessary to modify doses of cilazapril for the treatment of essential hypertension in uraemic patients. When creatinine clearance was below 15 ml min-1 cilazaprilat concentrations were increased, half-lives were prolonged and ACE inhibition remained above 90% for at least 24 h. A reduced dosage is indicated for these patients. 9. In patients requiring haemodialysis, maintenance doses of 0.5 mg given after each haemodialysis session are sufficient. [ABSTRACT FROM AUTHOR]

The transoropalatal approach to the atlantoaxial-clival area provides excellent exposure for neurosurgical decompression and fusion procedures. The technique has been effectively applied in the treatment of bony and soft tissue abnormalities of the anterior spinal region. Although this approach is safe and reliable, it is not part of the otolaryngologist's usual surgical armamentarium. In the present study, we describe the case histories of five patients who underwent resection of the odontoid process for cervicomedullary compression. Neurological compromise was manifested by progressive upper and/or lower extremity paresis in all patients. In each patient, a transoropalatal approach was used. The surgical technique is discussed, and the prevention of possible sequelae, including velopharyngeal incompetence and palatal or pharyngeal wound dehiscence, is addressed. [ABSTRACT FROM AUTHOR]

Compares the effects of antihypertensive regimens on patients with chronic renal failure in France. Comparison of the efficacy between angiotensin converting enzyme inhibitors and beta blockers; Administration of treatment following randomization; Measurement of supine blood pressure using mercury sphygmomanometer. INSET: Clinical implications.