A full nucleoprotein gene sequencing of 68 isolates collected from passive rabies surveillance system in Georgia between 2015 and 2016 identified two distinct dog rabies phylogroups, GEO_V1 and ...GEO_V2, which both belonged to the cosmopolitan dog clade. GEO_V1 was found throughout the country and was further divided into four sub-phylogroups that overlapped geographically; GEO_V2 was found in the southeast region and was closely related to dog rabies in Azerbaijan. A sequence analysis of the full N gene, partial nucleoprotein gene of N-terminal and C-terminal, and the amplicon sequences of pan-lyssavirus RT-qPCR LN34 showed that all four sequencing approaches provided clear genetic typing results of canine rabies and could further differentiate GEO_V1 and GEO_V2. The phylogenetic analysis results vary and were affected by the length of the sequences used. Amplicon sequencing of the LN34 assay positive samples provided a rapid and cost-effective method for rabies genetic typing, which is important for improving rabies surveillance and canine rabies eradication globally.
Abstract
Introduction
Systemic sclerosis (SS) is a rare connective tissue disorder characterized by widespread vascular dysfunction and progressive skin and internal organ fibrosis. Scleroderma renal ...crisis (SRC) is a life-threatening complication of SS. The estimated incidence of SSc is approximately 20 cases per million per year, and SRC affects about 5-15% of those patients.
Case Description
A 32-year-old female was admitted to the hospital with dyspnea, edema, HTN, COPD. 4 months before the hospitalization, she had an abrupt onset of HTN (230/120 mm/Hg) and seizures (no abnormal waveforms on EEG). Vital signs: HR 90’, RR 22’, BP 197/121 mmHg, SpO2 90% on room air. PEx: severe jugular venous dilation, crackles in both lungs, 3+ pitting edema bilaterally. The skin appeared abnormal with a modified Rodnan score “9” out of “51” with puffy hands, sclerodactyly, telangiectasia, and Raynaud's phenomena. Lab: creatinine 406 mcmol/L, urea 20.8 mmol/L, T.Ca 2.04 mmol/L, P 1.71 mmol/L, PTH 255.5 pg./mL, Alb 33 g/L, LDH 596 U/L. Urinalysis: UPCR of 4.169 mg/mg creat. microhematuria ANA were positive for centromere pattern with a titer of >400 AU/mL (N <40), CENP-B +++, negative for anti-Scl70, anti-dsDNA, ANCA, Anti-GBM, anti-CCP, RF, anti-Jo1 and anti-Smith antibodies. A kidney biopsy showed acute tubular injury in the early stage, and later stages of interstitial fibrosis and tubular atrophy; chronic active thrombotic microangiopathy (TMA), vascular abnormalities including intimal accumulation of myxoid material, thrombosis, fibrinoid necrosis consistent with Scleroderma Renal Crisis (Fig.3; 4; 5; 6; 7) The patient started treatment with losartan 100mg. 3 months later she started hemodialysis due to diuretic refractory overhydration with severe pulmonary edema resulting in multiple hospital readmissions.
Discussion
SRC is a dreaded complication of systemic sclerosis that is characterized by new-onset malignant hypertension and progressive acute renal failure, often with associated microangiopathic hemolytic anemia and thrombocytopenia, occurring in ≈ 5–15% of cases, of which 2% occur with the Limited cutaneous systemic sclerosis (lcSS) and 12% in the Diffuse cutaneous systemic sclerosis (dcSS). Histopathologically SRC can be divided into narrowly defined nd-SRC and SSc-associated TMA: nd-SRC is a typical type of SRC, which shows acute renal failure and abrupt onset of moderate-to-significant hypertension. The pathology of nd-SRC shows injured endothelial cells and subsequent intimal thickening in the arcuate and interlobular arteries. The pathology of SSc-TMA shows abnormalities in the capillary wall which eventually leads to microvascular thrombosis. Our case demonstrates severe damage to the kidney, presenting with combined nd-SRC and SSc-TMA, inevitabley leading to irreversible changes resulting in CKD. Notably, until the kidney histopathology workup, neither clinical presentation nor lab tests revealed typical TMA. SRC was at one time almost uniformly fatal, with death often occurring within a few weeks. With the development of ACE-I, survival has improved dramatically, but death rates remain unacceptably high. Unfortunately, some will require chronic dialysis. However, when timely and appropriately managed, renal function can improve considerably, although it may take several months to years, allowing for discontinuation of dialysis.
Conclusion
SSc should be considered in any patient presenting with malignant hypertension and AKI. SRC can occur in patients without evidence of skin thickening or other manifestations of SSc. Early diagnosis improves outcome. Kidney biopsy should be gold standard in all patients with ``unknown'' causes of the CKD. ACEi remains the cornerstone of the treatment. Renal Transplantation: to discuss after two years after start of dialysis.
We construct a uniformly bounded orthonormal almost greedy basis for the variable exponent Lebesgue spaces 𝐿𝑝(·)(0, 1), 1 < 𝑝– ≤ 𝑝+ ≤ 2 (or 2 ≤ 𝑝– ≤ 𝑝+ < ∞), when the diadic Hardy–Littlewood ...maximal operator is bounded on these spaces.
