Y-chromosome haplogroups and susceptibility to azoospermia factor c microdeletion in an Italian population

Background

A limited number of studies aimed at investigating the possible association of Y‐chromosome haplogroups with microdeletions of the azoospermia factors (AZFs) or with particular infertile phenotypes, but definitive conclusions have not been attained. The main confounding elements in these association studies are the small sample sizes and the lack of homogeneity in the geographical origin of studied populations, affecting, respectively, the statistical power and the haplogroup distribution.

Materials and methods

To assess whether some Y‐chromosome haplogroups are predisposing to, or protecting against, azoospermia factor c (AZFc; b2/b4) deletions, 31 north Italian patients carrying the AZFc b2/b4 microdeletion were characterised for 8 Y‐chromosome haplogroups, and compared with the haplogroup frequency shown by a north Italian population without the microdeletion (n = 93).

Results and discussion

A significant difference was observed between the two populations, patients with microdeletions showing a higher frequency of the E haplogroup (29.3% vs 9.7%, p<0.01). The geographical homogeneity of the microdeleted samples and of the control population, controlled at microgeographical level, allows the possibility that the geographical structure of the Y genetic variability has affected our results to be excluded.

Conclusion

Thus, it is concluded that in the north Italian population Y‐chromosome background affects the occurrence of AZFc b2/b4 deletions.Y‐chromosome long‐arm microdeletions are found in 5–10% of men with severe oligospermia and non‐obstructive azoospermia, and encompass one or more azoospermia factor (AZF) loci. Deletions of the azoospermia factor c (AZFc) region are clearly among the most commonly known molecular causes of spermatogenic failure in men.¹ These deletions are caused by homologous recombination between the 229‐kb‐long b2 and b4 amplicons² and span 3.5 Mb. Eight different gene families are removed by AZFc deletions, including all members of the DAZ gene family, which represents the stronger candidate for the AZFc phenotype.^{1,2,3,4,5,6,7} Although all AZFc deletions are essentially identical in molecular extension, people carrying these microdeletions present variable infertile phenotypes, suggesting the involvement of environmental factors and/or other genetic regions. Furthermore, the function of the AZF genes in human spermatogenesis and the role of the Y‐chromosome background in the predisposition to occurrence of deletions is still largely unknown.At present, around 250 Y single‐nucleotide polymorphisms have been discovered and their phylogenetic relationships are well known.⁸ These polymorphic markers of the male‐specific region of the Y chromosome define monophyletic groups of the Y chromosome, which hereafter we will name as “haplogroups”.A limited number of studies have investigated the possible association of Y‐chromosome haplogroups with microdeletions or with a particular infertile phenotype,⁹ but the contribution of predisposing factors or genetic background to causing deletions is still debated. In particular, only three studies have investigated the possible association between Y‐chromosome haplogroups and AZF deletions,^10,11,12 all of them failing to establish important associations. These works studied such associations in an European population involving 73 microdeleted samples of heterogeneous geographical origin,¹⁰ in a northwestern European population involving 50 patients¹¹ and in a Japanese population, more geographically localised but represented by a very low number of people with microdeletions (six patients).¹² All the previous studies that found some suggestion of an association with Y‐chromosome haplogroups dealt with infertility. They reported a considerable over‐representation of the haplogroup K(xL,N,O1,O3c,P) in Danish men with reduced sperm count, which did not reach significance probably because of a small sample size,¹³ and D2b Y lineage in Japanese men with reduced sperm count,¹⁴ not confirmed by a later study.¹²However, these association studies require particular attention to two principal factors: (1) the geographical structure of the Y‐chromosome variations in the population under investigation, because the Y‐chromosome genetic variability is highly geographically structured and the Y‐haplogroup distribution changes over different geographical areas¹⁵; and (2) the number and selection criteria of the patient and control groups.To assess whether some Y‐chromosome haplogroups predispose to, or protect against, AZFc deletion, we have defined and compared Y‐chromosome haplogroup distribution in a group of unrelated Italian infertile men harbouring the b2/b4 deletion (n = 41, 31 of whom were from north Italy) and in a control group represented by fertile men without microdeletions (fathers of at least one child) from north Italy (n = 93).     

Multiple sclerosis in patients with hereditary spastic paraplegia: a case report and systematic review

Neurological Sciences - An increasing number of cases of comorbid hereditary spastic paraplegia (HSP) and multiple sclerosis (MS) have been described. We report a patient with the SPG3A form of HSP...     

Microsurgical reconstruction of the isolated columellar defect with a prelaminated radial forearm free flap. A case report and a review of the literature

The columella is one of the smallest subunits of the nose, but the loss of this structure has important aesthetic and structural implications. Few papers in literature present microsurgical techniques for the reconstruction of an isolated columellar defect. This report describes the use of a prelaminated radial forearm free flap (RFFF) for the reconstruction of an isolated columellar defect and reviews the current literature. A 45-year-old woman presented to our Unit with a history of palate squamous cell carcinoma and severe nasal deformity with an almost complete loss of the columella. A prelaminated RFFF with the fifth rib was used for a two-staged reconstruction of the isolated columellar defect. The radial pedicle was anastomosed to the facial vessels and the postoperative course was uneventful. Complete survival of the flap was achieved and, 10 months postoperatively, the patient had bilateral nasal patency, with an increased tip projection and a good aesthetic result. A prelaminated RFFF can be considered a valuable reconstructive option in cases of a large composite defect of the columella and limited availability of adjacent tissues.     

Prevalence of renal disease within an urban HIV-infected cohort in northern Italy

Background

Renal disease is an increasingly recognized noninfectious comorbidity associated with human immunodeficiency virus (HIV) infection.

Methods

Our retrospective, cross-sectional study evaluated prevalence of nephropathy among HIV-infected patients followed up in our outpatient clinic during the year 2011. Renal dysfunction and chronic kidney disease (CKD) were defined as estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m² and as renal damage or eGFR <60 ml/min per 1.73 m² over a 3-month or greater period, respectively.

Results

We enrolled 894 HIV-infected patients with a mean age of 44.2 years and a mean current CD4 lymphocyte count of 508 cells/mm³. The prevalence of renal dysfunction and CKD was 27.4 and 21.3 %, respectively. Older age, male gender, hypertension, diabetes, proteinuria, hypertriglyceridemia, lower nadir CD4 cell count, current use of tenofovir or tenofovir plus a ritonavir-boosted protease inhibitor were independently associated with renal dysfunction.

Conclusion

Renal dysfunction is a frequent comorbidity among HIV-infected persons and requires a careful clinical and laboratory monitoring of renal function.     

Phage-Displayed Peptides for Targeting Tyrosine Kinase Membrane Receptors in Cancer Therapy

Receptor tyrosine kinases (RTKs) regulate critical physiological processes, such as cell growth, survival, motility, and metabolism. Abnormal activation of RTKs and relative downstream signaling is implicated in cancer pathogenesis. Phage display allows the rapid selection of peptide ligands of membrane receptors. These peptides can target in vitro and in vivo tumor cells and represent a novel therapeutic approach for cancer therapy. Further, they are more convenient compared to antibodies, being less expensive and non-immunogenic. In this review, we describe the state-of-the-art of phage display for development of peptide ligands of tyrosine kinase membrane receptors and discuss their potential applications for tumor-targeted therapy.     

Impact of Aspirin on clinical outcome in advanced HCC patients receiving sorafenib and regorafenib

Background and aimThe aim of our retrospective study is to evaluate the prognostic significance of aspirin in patients with advanced HCC treated with sorafenib.Methods304 patients with HCC,consecutively treated with sorafenib from May 2007 to September 2018, were included in the clinical study. Of Them 93 patients token aspirin. Progression-free survival (PFS)and overall survival (OS)were estimated with the Kaplan–Meier method and compared with the log-rank test.ResultsThe concomitant use of sorafenib and aspirin was associated with a median OS of 18.3 months compared to 8.8 months of patients who did not receive aspirin (HR 0.57; P < 0.0001). The concomitant use of sorafenib and aspirin was associated with a median PFS of 7.3 months compared to 3.0 months of patients who did not receive aspirin (HR 0.61; P = 0.0003). In the multivariate analysis, the use of aspirin maintained an independent prognostic value for OS(HR 0.61; P = 0.0013). In second line the concomitant use of regorafenib and aspirin was associated with a median OS of 16.9 months compared to 8.0 months of patients who did not receive aspirin (HR 0.30; P = 0.02).ConclusionGlobally, our data seem to suggest that aspirin use may improve the clinical outcome of patients with advanced hepatocellular carcinoma receiving sorafenib and regorafenib.     

COVID-19 in IBD: The experience of a single tertiary IBD center

BackgroundItaly has been one of the most affected countries in the world by COVID-19. There has been increasing concern regarding the impact of COVID‐19 on patients with inflammatory bowel disease (IBD), particularly in patients treated with immunosuppressants or biologics. The aim of our study is to understand the incidence of COVID-19 in a large cohort of patients with IBD. Furthermore, we analyzed possible risk factors for infection and severity of COVID-19.MethodsThis was an observational study evaluating the impact of COVID-19 on IBD patients in a single tertiary center. A 23 multiple-choice-question anonymous survey was administered to 1200 patients with IBD between March 10th and June 10th 2020.Results1158 questionnaires were analyzed. The majority of patients had Crohn's disease (CD) (60%) and most of them were in clinical remission. Among the 26 patients (2.2%) who tested positive for COVID-19, only 5 (3CD) were on biological treatment and none required hospitalization. Two patients died and were on treatment with mesalazine only. Of the 1158 patients, 521 were on biological therapy, which was discontinued in 85 (16.3%) and delayed in 195 patients (37.4%). A worsening of IBD symptoms was observed in 200 patients on biological therapy (38.4%). Most of these patients, 189 (94.5%), had stopped or delayed biological treatment, while 11 (5.5%) had continued their therapy regularly (p<0.001).ConclusionsOur data are in line with the current literature and confirm a higher incidence compared to the general population. Biological therapy for IBD seems to not be a risk factor for infection and should not be discontinued in order to avoid IBD relapse.