Abstract
STUDY QUESTION
Are JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) infections associated with spontaneous abortion (SA)?
SUMMARY ANSWER
There is no association of JCPyV or BKPyV with SA.
...WHAT IS KNOWN ALREADY
A large number of risk factors have been associated with SA. The role of polyomaviruses, including JCPyV and BKPyV, in SA remains to be clarified.
STUDY DESIGN, SIZE, DURATION
This is a case–control study including women affected by spontaneous abortion (SA, n = 100, the cases) and women who underwent voluntary interruption of pregnancy (VI, n = 100, the controls).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Viral DNAs were investigated by qualitative PCR and quantitative droplet-digital PCR (ddPCR) in matched chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from SA (n = 100) and VI (n = 100). Indirect ELISAs with mimotopes/synthetic peptides corresponding to JCPyV and BKPyV viral capsid protein 1 epitopes were then employed to investigate specific IgG antibodies against JCPyV and BKPyV in human sera from SA (n = 80) and VI (n = 80) cohorts.
MAIN RESULTS AND THE ROLE OF CHANCE
JCPyV DNA was detected in 51% and 61% of SA and VI samples, respectively, with a mean viral DNA load of 7.92 copy/104 cells in SA and 5.91 copy/104 cells in VI (P > 0.05); BKPyV DNA was detected in 11% and 12% of SA and VI specimens, respectively, with a mean viral DNA load of 2.7 copy/104 cells in SA and 3.08 copy/104 cells in VI (P > 0.05). JCPyV was more prevalent than BKPyV in both SA and VI specimens (P < 0.0001). In PBMCs from the SA and VI cohorts, JCPyV DNA was detected with a prevalence of 8% and 12%, respectively, with a mean viral DNA load of 2.29 copy/104 cells in SA and 1.88 copy/104 cells in VI (P > 0.05). The overall prevalence of serum IgG antibodies against JCPyV detected by indirect ELISAs was 52.5% and 48.7% in SA and VI groups, respectively, whereas BKPyV-positive sera were found in 80% SA and 78.7% VI samples.
LIMITATIONS, REASONS FOR CAUTION
This study did not investigate the presence of viral mRNA and/or proteins, which are indicative of an active viral infection, and these might be taken into consideration in future studies.
WIDER IMPLICATIONS OF THE FINDINGS
JCPyV and BKPyV DNA sequences were detected and quantitatively analyzed for the first time by PCR/ddPCR in chorionic villi tissues and PBMCs from SA and VI specimens. Moreover specific immunological approaches detected serum IgG against JCPyV/BKPyV. Statistical analyses, however, do not indicate an association between these polyomaviruses and SA.
STUDY FUNDING/COMPETING INTEREST(s)
This work was supported by the University of Ferrara, FAR research grants and the University Hospital of Ferrara/University of Ferrara joint grant. No potential conflicts of interest were disclosed.
This work introduces the G-Fly-Crane, a proof-of-concept aerial multi-robot system designed to demonstrate the advantage of using multiple aerial robots as a valuable tool for novel construction ...techniques, not requiring the use of heavy engines and costly infrastructures. We experimentally demonstrate its capability to perform pick-and- place and manipulation tasks in a construction scenario, with an increased payload capacity and dexterity compared to the single robot case. The system is composed of three aerial robots connected to a platform by three pairs of cables. The platform is equipped with a gripper, enabling the grasping of objects. The paper describes in detail the hardware and software architecture of our prototype and explains the implemented control methods. A shared control strategy incorporates the human operator in the control loop, thus increasing the overall system reliability when performing complex tasks. The paper also discusses the next steps required to bring this technology from indoor laboratory conditions to real-world applications. Keywords Aerial robotics * Multi-robot systems * Shared control * Novel construction techniques
STUDY QUESTION
Is the methylation status of the methylenetetrahydrofolate reductase (MTHFR) promoter region in semen samples associated with ‘recurrent spontaneous abortion’ (RSA)?
SUMMARY ANSWER
...MTHFR promoter hypermethylation is more frequent in semen samples from RSA couples than in semen samples from infertile couples with no history of RSA (NRSA) and affects the whole sperm population significantly more often.
WHAT IS KNOWN ALREADY
Modifications to the MTHFR gene such as polymorphisms and promoter methylations are associated with male infertility.
STUDY DESIGN, SIZE AND DURATION
Retrospective cohort study of semen samples from 20 RSA couples, 147 NRSA couples and 20 fertile men between 2011 and 2012.
MATERIALS, SETTING AND METHODS
DNA from the semen samples of RSA, NRSA and fertile men were analyzed by methylation-specific PCR amplification using primers which anneal to the methylated or unmethylated cytosine-phosphodiester bond guanine (CpG) islands within the promoter region of MTHFR. The specificity of the PCR products was assessed by DNA sequencing.
MAIN RESULTS AND THE ROLE OF CHANCE
The methylated MTHFR epigenotype (including samples where it co-existed with unmethylated MTHFR epigenotypes) was detected in 75% of RSA men, 54% of NRSA men and 15% of fertile men. MTHFR methylation was observed in the whole sperm population in semen samples from 55% of RSA men compared with 8% in NRSA men (P < 0.05) and 0% in fertile men (P < 0.05). DNA sequencing analysis was fully concordant with the PCR results and revealed that when MTHFR methylation occurred, CpG islands within the promoter region were 100% methylated (hypermethylation of MTHFR promoter).
LIMITATIONS, REASONS FOR CAUTION
The relatively small sample size of RSA infertile couples.
WIDER IMPLICATIONS OF THE FINDINGS
The hypermethylation of the MTHFR gene promoter should be taken into consideration as a novel putative risk factor in RSA etiology.
STUDY FUNDING/COMPETING INTEREST(S)
Our institution has received an FAR research grant from the University of Ferrara, Ferrara, Italy. No competing interests declared.
Abstract Objective Human papillomavirus (HPV) DNA testing is used increasingly for measuring the outcome of treatment for high-grade cervical intra-epithelial neoplasia (CIN2+). However, there is no ...international consensus regarding the number of tests and follow-up visits necessary in the post-treatment surveillance. A negative HPV DNA test result may permit relaxing the intensive post-treatment surveillance, but this possibility has not been standardized by all institutions to date. Study design In 2008, the surveillance programme covering the Emilia-Romagna region in northern Italy adopted the HPV DNA test as a routine tool in the follow-up of women treated for CIN2+. Data from a prospective 5-year study are reported herein. Three hundred and ten patients treated for CIN2+ with a loop electrosurgical excision procedure underwent HPV DNA testing, cytology and colposcopy at 6 months post treatment. If all three tests were negative, women were tested at 18 months with cytology and colposcopy. If any of the three tests were positive, women were tested at 12, 18 and 24 months with cytology and colposcopy. When appropriate, a colposcopy-directed biopsy or CIN2+ retreatment was performed. After 18–24 months, the patients were tested annually with cytology for 3 years. Results None of the 172 (55%) women who were HPV negative at 6 months were found to have residual/recurrent CIN2+ during the surveillance period. In contrast, among the 138 (45%) HPV-positive women, 17 cases of residual/recurrent CIN2+ (17/138; 12.3%) were identified between 6 and 24 months. Conclusion HPV DNA testing at six months after treatment for CIN2+ effectively identifies women who are disease free (HPV negative), and for whom a single follow-up at 18 months is sufficient.
Purpose
Tuberculosis (TB) of the eye is a well-known extrapulmonary localization in high-incidence countries. Data on its relevance in developed countries are scanty. We aim to study the ...epidemiological and clinical pattern of ocular TB in a tertiary care institution of a western country.
Methods
From 2007 to 2010, consecutive patients with a diagnosis of isolated ocular TB or associated to extraocular TB were recruited. Patients with ophthalmological and clinical features of TB were treated with standard antitubercular therapy (ATT) and steroids in case of concomitant severe ocular inflammation.
Results
Seventeen cases of ocular and extraocular TB and 45 cases of isolated ocular TB were identified. The proportion of patients with ocular and extraocular TB in our local district was 8.1 %, with a proportion of 10.6 % for the isolated cases. In Cohort 1, only one patient was symptomatic for ocular impairment, and uveitis without inflammation was the most common presentation. On the contrary, in Cohort 2, all patients had visual impairment, mainly with bilateral involvement. 77.8 % of the patients showed an inflammatory pattern. ATT was administered for at least 9 months, in four cases with a short course of systemic corticosteroids. Eight cases in Cohort 2 showed recurrence after 1 year from diagnosis.
Conclusions
TB of the eye should not be forgotten, even in geographical areas not considered among endemic countries. Ocular evaluation is advisable in patients with pulmonary and extrapulmonary TB, as early detection may allow ATT to preserve visual acuity.
Purpose
Spine fusion is the gold standard treatment in degenerative and traumatic spine diseases. The bone regenerative medicine needs (i) in vitro functionally active osteoblasts, and/or (ii) the in ...vivo induction of the tissue. The bone tissue engineering seems to be a very promising approach for the effectiveness of orthopedic surgical procedures, clinical applications are often hampered by the limited availability of bone allograft or substitutes. New biomaterials have been recently developed for the orthopedic applications. The main characteristics of these scaffolds are the ability to induce the bone tissue formation by generating an appropriate environment for (i) the cell growth and (ii) recruiting precursor bone cells for the proliferation and differentiation. A new prototype of biomaterials known as “bioceramics” may own these features. Bioceramics are bone substitutes mainly composed of calcium and phosphate complex salt derivatives.
Methods
In this study, the characteristics bioceramics bone substitutes have been tested with human mesenchymal stem cells obtained from the bone marrow of adult orthopedic patients.
Results
These cellular models can be employed to characterize in vitro the behavior of different biomaterials, which are used as bone void fillers or three-dimensional scaffolds.
Conclusions
Human mesenchymal stem cells in combination with biomaterials seem to be good alternative to the autologous or allogenic bone fusion in spine surgery. The cellular model used in our study is a useful tool for investigating cytocompatibility and biological features of HA-derived scaffolds.
Background:
The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant ...active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown.
Objective:
To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis.
Methods:
We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing–remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls.
Results:
Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively).
Conclusion:
Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity.
Background:
The relevance of human leukocyte antigen (HLA)-G in dimeric form in multiple sclerosis (MS) is still unknown.
Objective:
To investigate the contribution of cerebrospinal fluid (CSF) HLA-G ...dimers in MS pathogenesis.
Methods:
CSF amounts of 78-kDa HLA-G dimers were measured by western blot analysis in 80 MS relapsing–remitting MS (RRMS) patients and in 81 inflammatory and 70 non-inflammatory controls.
Results:
CSF amounts of 78kDa HLA-G dimers were more frequent in RRMS than in inflammatory (p<0.01) and non-inflammatory controls (p<0.001) and in magnetic resonance imaging (MRI) inactive than in MRI active RRMS (p<0.00001).
Conclusion:
Our findings suggest that HLA-G dimers may be implicated in termination of inflammatory response occurring in MS.
Background and purpose
It has been demonstrated that inflammation may contribute to epileptogenesis and cause neuronal injury in epilepsy. In this study, the prevalence of antibodies to simian virus ...40 (SV40), a kidney and neurotropic polyomavirus, was investigated in serum samples from 88 epileptic children/adolescents/young adults.
Methods
Serum antibodies reacting to specific SV40 peptides were analysed by indirect enzyme‐linked immunosorbent assay. Synthetic peptides corresponding to the epitopes of viral capsid proteins 1–3 were used as SV40 antigens.
Results
A significantly higher prevalence of antibodies against SV40 was detected in sera from epileptic patients compared to controls (41% vs. 19%). Specifically, the highest significant difference was revealed in the cohort of patients from 1.1 to 10 years old (54% vs. 21%), with a peak in the sub‐cohort of 3.1–6 years old (65% vs. 18%).
Conclusion
Our immunological data suggest a strong association between epilepsy and the SV40 infection.
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