Searching for archaic contribution in Africa

Abstract

Context: Africa’s role in the narrative of human evolution is indisputably emphasised in the emergence of Homo sapiens. However, once humans dispersed beyond Africa, the history of those who stayed remains vastly under-studied, lacking the proper attention the birthplace of both modern and archaic humans deserves. The sequencing of Neanderthal and Denisovan genomes has elucidated evidence of admixture between archaic and modern humans outside of Africa, but has not aided efforts in answering whether archaic admixture happened within Africa.

Objectives: This article reviews the state of research for archaic introgression in African populations and discusses recent insights into this topic.

Methods: Gathering published sources and recently released preprints, this review reports on the different methods developed for detecting archaic introgression. Particularly it discusses how relevant these are when implemented on African populations and what findings these studies have shown so far.

Results: Methods for detecting archaic introgression have been predominantly developed and implemented on non-African populations. Recent preprints present new methods considering African populations. While a number of studies using these methods suggest archaic introgression in Africa, without an African archaic genome to validate these results, such findings remain as putative archaic introgression.

Conclusion: In light of the caveats with implementing current archaic introgression detection methods in Africa, we recommend future studies to concentrate on unravelling the complicated demographic history of Africa through means of ancient DNA where possible and through more focused efforts to sequence modern DNA from more representative populations across the African continent.     

Renal C3 synthesis in idiopathic membranous nephropathy: correlation to urinary C5b-9 excretion

Renal C3 synthesis in idiopathic membranous nephropathy: Correlation to urinary C5b-9 excretion. BACKGROUND: Complement activation plays a central pathogenetic role in idiopathic membranous nephropathy (IMN). Urinary excretion of C5b-9 correlates to the immunologic activity of this disease. Recently, renal cortical C3 gene expression has been described in several nephropathies. METHODS: The aim of this study was to investigate the renal C3 gene expression by in situ hybridization in IMN and to correlate it with histopathologic, pathophysiologic, and immunologic (urinary C5b-9) indices of disease activity. RESULTS: C3 was expressed in 77% of 22 renal biopsies of IMN patients, mainly at the cortical tubular and glomerular parietal epithelial cell levels. C3 protein synthesis by tubular cells was demonstrated by immunofluorescence. The intensity of C3 gene expression by both glomerular and tubulointerstitial compartments correlated with the glomerular stage of disease (P = 0. 0023 and P = 0.0214, respectively). Although no correlation was found with proteinuria, serum creatinine at renal biopsy time was strongly associated with renal C3 expression. IMN patients showed a trend of increased urinary C5b-9 levels, which correlated to C3 at the tubulointerstitial level (P = 0.0143). CONCLUSION: Renal C3 production, mainly at the tubular level, may be induced by urinary excretion of C5b-9 in IMN and may have a pathogenetic role in the tubulointerstitial damage that can be associated with this disease.     

Laparoscopic treatment of pediatric varicocele: a multicenter study of the italian society of video surgery in infancy

PURPOSE: We report preliminary results of a multicenter study of the Italian Society of Video Surgery in Infancy on the laparoscopic treatment of pediatric varicocele. MATERIALS AND METHODS: A total of 161 children 6 to 16 years old (median age 12.5) underwent laparoscopic treatment of varicocele at 6 pediatric surgery divisions. Varicocele was on the left side in 159 cases (98.7%) and bilateral in 2 (1.3%). Two boys had recurrent left varicocele. All children were treated with laparoscopy, including ligation of the spermatic veins only in 28 (17.3%), and ligation of the testicular veins and artery in 133 (82.7%). In 10 boys (6.2%) an additional procedure was done simultaneously, including closure of an apparently patent peritoneal vaginal duct on the right side in 7 and resection of epiploic adhesions between the intestinal loops and abdominal wall from previous appendectomy in the remaining 3. RESULTS: Average operative time was 30 minutes and hospitalization was about 24 hours. At followup there were 13 minor complications (8%), including left hydrocele in 9 children who underwent the Palomo technique, minor scrotal emphysema in 2 and umbilical granuloma in 2. In our series varicocele recurred in 1 boy (3.5%) who underwent ligation of the spermatic veins only and in 3 (2.2%) treated with the Palomo technique. CONCLUSIONS: Our preliminary experience shows that the results of the laparoscopic approach are comparable to those of the open approach. However, the important advantages of laparoscopy over the open approach are its minimal invasiveness and precision of intervention. Moreover, laparoscopy allows treatment of other intra-abdominal pathological conditions using the same anesthesia, as in 10 patients in our series. We believe that ligating the testicular veins and artery is preferable to ligating the testicular veins only, even if the incidence of hydrocele is not negligible after the Palomo procedure.     

Effective and safe off-label use of caplacizumab treatment in a middle-aged obese male

This study shows clinical efficacy and safety profile of an off-label use of caplacizumab for the treatment of immune-mediated thrombotic thrombocytopenic purpura in a middle-aged obese male patient manifesting aphasia, weakness and unconsciousness. Routine blood tests revealed haemolytic anaemia, severe thrombocytopenia (platelet count = 20 × 10⁹/L) and moderate creatinine increase. Diagnosis was based on the clinical judgement and laboratory determinations (undetectable ADAMTS13 activity and presence of anti-ADAMTS13 antibodies). The patient underwent plasma-exchange and an adjunctive treatment with prednisone (1 mg/Kg/day), but the occurrence of a refractory and exacerbated form of disease suggested also using rituximab (375 mg/m² weekly for 4 weeks) and caplacizumab as salvage treatments. The caplacizumab was given at 10 mg/day subcutaneously without the first intravenous bolus. Because von Willebrand factor inhibition, platelet count recovery and remission of symptoms were achieved, use of caplacizumab with this scheme appeared to be as effective as the approved one. Although this is an off-label use, this case highlights the potential of this new treatment, in terms of drug's efficacy and safety.     

Comparison of safety and efficacy of bivalirudin versus unfractionated heparin in high-risk patients undergoing percutaneous coronary intervention (from the Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin study)

Bivalirudin, a direct thrombin inhibitor, is as effective as unfractionated heparin (UFH), with decreased bleeding in patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI). The aim of this study was to evaluate the effectiveness of bivalirudin versus UFH in selected PCI patients at high bleeding risk. Four hundred one consecutive patients who underwent PCI fulfilling ≥ 1 enrollment criterion (age >75 years, chronic renal failure, and diabetes mellitus) were randomized to bivalirudin (bolus 0.75 mg/kg followed by infusion during the procedure; n = 198) or UFH (75 IU/kg; n = 203). In the overall population, 39% were aged >75 years, 22% had renal failure, 63% had diabetes, and 29% had acute coronary syndromes. The primary efficacy end point was the 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, stent thrombosis, or target vessel revascularization). The primary safety end point was the occurrence of any bleeding or entry-site complications after PCI. All patients were preloaded with clopidogrel 600 mg. Glycoprotein IIb/IIIa inhibitors were used at the operators' discretion. Thirty-day major adverse cardiac event rates were 11.1% in the bivalirudin group and 8.9% in the UFH group (p = 0.56); the primary efficacy end point was reached mainly because of periprocedural myocardial infarction; 1 patient in the bivalirudin group had stent thrombosis. Occurrence of the primary safety end point was 1.5% in the bivalirudin group and 9.9% in the UFH group (p = 0.0001); this benefit was essentially driven by the prevention of entry-site hematomas >10 cm (0.5% vs 6.9%, p = 0.002). In conclusion, Anti-Thrombotic Strategy for Reduction of Myocardial Damage During Angioplasty-Bivalirudin vs Heparin (ARMYDA-7 BIVALVE) indicates that bivalirudin, compared with UFH, causes significantly lower bleeding and has a similar incidence of major adverse cardiac events in patients with older age, diabetes mellitus, or chronic renal failure who undergo PCI.     

Myocarditis with ST-Elevation Myocardial Infarction presentation in young man. A case series of 11 patients

Acute myocarditis may mimic an infarction. Aim is to describe a case series of peculiar myocarditis. From 1997 to 2003, 11 male patients (age 17-39 years) were admitted with diagnosis of acute myocardial infarction, localized ST segment elevation and minimal enzyme release. Ten patients had fever in the 3 days prior to admission. Eight patients underwent coronary angiography showing normal coronary arteries. All remained asymptomatic at long term follow-up. In conclusion, myocarditis with ST elevation myocardial infarction presentation is an acute benign syndrome especially frequent in young males.     

Italian multicenter survey on laparoscopic treatment of gastro-esophageal reflux disease in children

Background: Skepticism is still present today about the laparoscopic treatment of gastro-esophageal reflux (GER) in children. We present the prospective experience and short-term results of eight Italian pediatric surgical units. Methods: We included all the children with complicated GER, operated after January 1998 by single surgeons from eight different centers. Diagnostic aspects, type of fundoplication, and complications were considered. All the patients were followed for a minimum period of 6 months in order to detect complications or recurrences. Results: 288 children were prospectively included. Mean age was 4.8 years (3 m–14 y). Nissen fundoplication was done in 25%, floppy Nissen in 63%, Toupet in 1.7%, and anterior procedures (Lortat Jacob, Thal) in 10%. Gastrostomy was associated, if neurological impairment or feeding disorders were present. Mean follow-up was 15 months and reoperation was necessary in 3.8% of cases. Conclusions: This experience underlines that minimal invasive access surgery in children is safe and that the laparoscopic approach is considered in eight centers the golden standard for surgical repair of gastro-esophageal reflux disease maintaining the same indications and techniques of the open approach.