Tissue persistence of parvovirus B19 genotypes in asymptomatic persons

Parvovirus B19 (B19V) can persist in immunocompetent symptomatic and non-symptomatic individuals, as demonstrated by the finding of viral DNA in different tissues, in absence of viremia and of anti-B19V IgM. The spread and the nature of this phenomenon have not been clearly determined. In order to investigate the frequency of persistence and the tissue distribution of the three genotypes of B19V, the viral load of the persistent virus and its expression in the affected tissues, 139 tissue samples and 102 sera from 139 asymptomatic individuals have been analyzed by consensus PCRs and genotype specific PCRs for B19V detection and genotyping. Viral load was measured by real time PCR and viral mRNAs were detected by RT-PCR. Altogether, 51% individuals carried B19V DNA, more frequently in solid tissues (65%) than in bone marrow (20%). Genotype 1 was found in 28% tissue samples, genotype 2 in 68% and genotype 3 in 3% only. Viral load ranged from less then 10 copies to 7 x 10(4) copies per 10(6) cells, with the exception of two samples of myocardium with about 10(6) copies per 10(6) cells. mRNA of capsid proteins was present in two bone marrow samples only. In conclusion, in asymptomatic individuals B19V persistence is more common in solid tissues than in bone marrow, and genotype 2 persists more frequently than genotype 1. The results suggest that the virus persists without replicating, at sub-immunogenic levels.     

Changes in Food Choice,Taste, Desire,and Enjoyment 1 Year after Sleeve Gastrectomy: A Prospective Study

Obesity is a well-recognized global health problem, and bariatric surgery (BS)-induced weight reduction has been demonstrated to improve survival and obesity-related conditions. Sleeve gastrectomy (SG) is actually one of the most performed bariatric procedures. The underlying mechanisms of weight loss and its maintenance after SG are not yet fully understood. However, changes to the taste function could be a contributing factor. Data on the extent of the phenomenon are limited. The primary objective was to assess, through validated questionnaires, the percentage of patients who report an altered perception of post-SG taste and compare the frequency of intake of the different food classes before SG and after 1 year follow-up. The secondary objective was to evaluate the total body weight change. Materials and Methods: We prospectively investigated the changes in food choice and gustatory sensitivity of 52 patients (55.8% females) 12 months after SG. The mean initial weight and body mass index (BMI) were 130.9 ± 24.7 kg and 47.4 ± 7.1 kg/m², respectively. The frequency of food intake was assessed by food-frequency questionnaire, while changes in taste perception were assessed using the taste desire and enjoyment change questionnaire. The change in total body weight was also assessed. Results: A significant decrease in the intake frequency of bread and crackers (p < 0.001), dairy products and fats (p < 0.001), sweets and snacks (p < 0.001) and soft drinks (p < 0.001), and a significant increase in the frequency of vegetable and fruit consumption (p < 0.001) were observed at 12 months after SG in both genders. On the contrary, we found no significant changes in the frequency of meat and fish intake in females (p = 0.204), whereas a significant change was found in males (p = 0.028). Changes in perceived taste intensity of fatty foods (p = 0.021) and tart foods (p = 0.006) for females and taste of bitter foods for females and males (p = 0.002; p = 0.017) were found. Regarding the change in food desire for both genders, there was a decrease in the desire for sweet, fatty, and salty foods, whereas there was an increasing trend in the desire for tart foods, especially for females. Significant reduction in total body weight and BMI was observed in both genders at the time of follow-up. Conclusions: Based on our findings, we are able to support the evidence that changes in taste, desire, and enjoyment of taste are very common after SG, with a reduced preference for food with high sugar and fat content and an increased postoperative preference for low-sugar and -fat foods. However, further investigation is needed to clarify this issue. The molecular, hormonal, and central mechanisms underlying these changes in taste perception need to be further elucidated, as they could identify new targets able to modify obesogenic eating behavior, opening up a novel personalized therapeutic approach to obesity.     

Low-Power Laser Powder Bed Fusion Processing of Scalmalloy®

Among recently developed high-strength and lightweight alloys, the high-performance Scalmalloy^® certainly stands out for laser powder bed fusion (LPBF) production. The primary goal of this study was to optimize the Scalmalloy^® LPBF process parameters by setting power values suitable for the use of lab-scale machines. Despite that these LPBF machines are commonly characterized by considerably lower maximum power values (around 100 W) compared to industrial-scale machines (up to 480 W), they are widely used when quick setup and short processing time are needed and a limited amount of powder is available. In order to obtain the optimal process parameters, the influence of volumetric energy density (VED) on the sample porosity, microstructure and mechanical properties was accurately studied. The obtained results reveal the stability of the microstructural and mechanical behaviour of the alloy for VEDs higher than 175 Jmm⁻³. In this way, an energy-and-time-saving choice at low VEDs can be taken for the LPBF production of Scalmalloy^®. After identifying the low-power optimized process parameters, the effects of the heat treatment on the microstructural and mechanical properties were investigated. The results prove that low-VED heat-treated samples produced with an LPBF lab-scale machine can achieve outstanding mechanical performance compared with the results of energy-intensive industrial production.     

Phase I study of O6-benzylguanine and temozolomide administered daily for 5 days to pediatric patients with solid tumors.

PURPOSE: This pediatric phase I trial of O6-benzylguanine (O6BG) and temozolomide (TMZ) on a daily schedule for 5 days, every 28 days was performed to determine the maximum-tolerated dose of TMZ when given with a biologically active dose of O6BG and to define the toxicity profile of the combination in children with solid tumors. PATIENTS AND METHODS: Patients < or = 21 years old with refractory solid tumors were eligible. O6BG was administered intravenously over 60 minutes daily for 5 days. TMZ was administered orally 30 minutes after completion of each O6BG infusion. Starting doses of O6BG and TMZ were 60 mg/m2/d and 28 mg/m2/d, respectively. O6BG was escalated to 90 and 120 mg/m2/d; TMZ was subsequently escalated to 40, 55, 75, and 100 mg/m2/d. Cycles were repeated every 28 days. RESULTS: Forty-one patients were enrolled; 32 patients were assessable for toxicity. The combination of O6BG and TMZ was tolerable at TMZ doses less than half of the conventional dose of 200 mg/m2/d. Myelosuppression occurred sporadically at all dose levels and was the dose-limiting toxicity (DLT) at 100 mg/m2/d of TMZ combined with 120 mg/m2/d O6BG. Nonhematologic toxicities were generally mild. Evidence of antitumor activity was observed at 120 mg/m2/d O6BG combined with TMZ doses of 55 mg/m2/d and above. CONCLUSION: The recommended doses of O6BG administered with TMZ on a 5-day schedule in children are 120 mg/m2/d of O6BG and 75 mg/m2/d of TMZ. Evidence of activity was observed at these doses. Myelosuppression was the DLT.     

Myopia control in Mendelian forms of myopia

Purpose

To study the effectiveness of high-dose atropine for reducing eye growth in Mendelian myopia in children and mice.

Methods

We studied the effect of high-dose atropine in children with progressive myopia with and without a monogenetic cause. Children were matched for age and axial length (AL) in their first year of treatment. We considered annual AL progression rate as the outcome and compared rates with percentile charts of an untreated general population. We treated C57BL/6J mice featuring the myopic phenotype of Donnai–Barrow syndrome by selective inactivation of Lrp2 knock out (KO) and control mice (CTRL) daily with 1% atropine in the left eye and saline in the right eye, from postnatal days 30–56. Ocular biometry was measured using spectral-domain optical coherence tomography. Retinal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography.

Results

Children with a Mendelian form of myopia had average baseline spherical equivalent (SE) –7.6 ± 2.5D and AL 25.8 ± 0.3 mm; children with non-Mendelian myopia had average SE −7.3 ± 2.9 D and AL 25.6 ± 0.9 mm. During atropine treatment, the annual AL progression rate was 0.37 ± 0.08 and 0.39 ± 0.05 mm in the Mendelian myopes and non-Mendelian myopes, respectively. Compared with progression rates of untreated general population (0.47 mm/year), atropine reduced AL progression with 27% in Mendelian myopes and 23% in non-Mendelian myopes. Atropine significantly reduced AL growth in both KO and CTRL mice (male, KO: −40 ± 15; CTRL: −42 ± 10; female, KO: −53 ± 15; CTRL: −62 ± 3 μm). The DA and DOPAC levels 2 and 24 h after atropine treatment were slightly, albeit non-significantly, elevated.

Conclusions

High-dose atropine had the same effect on AL in high myopic children with and without a known monogenetic cause. In mice featuring a severe form of Mendelian myopia, atropine reduced AL progression. This suggests that atropine can reduce myopia progression even in the presence of a strong monogenic driver.     

Bone echinococcosis with hip localization: A case report with evaluation of imaging features

Hydatid disease (HD) is a zoonotic parasitic disease caused by the larvae of Echinococcus. Bone echinococcosis is rare, accounting for 0.5% to 4% of all echinococcosis. We describe a particular case of pelvic echinoccosis. A 29-year-old man initially presents with pain in his left hip for several years. After an accidental fall from a tree, he suffered a fracture of the left acetabulum. X-rays and CT scans showed an osteolytic area of the acetabulum with bony cortical interruption. MR imaging demonstrated extensive area of osteostructural alteration of the iliac wing and the left acetabulum due to multiple cysts with enhancement of the walls after administration of Gadolinium-based contrast agents. A CT-guided biopsy of an osteolytic area was performed with diagnosis of echinococcus cyst. He underwent albendazole therapy and subsequently echinococcus cyst exeresis, bone curettage, and left hip arthroplasty. Twenty-two months after surgery, CT scan showed recurrence of disease. After 4 years and 6 months of chronic therapy CT scan showed an increase in size of the cyst at the site of the disease recurrence. Five years and 4 months after the first operation, a new cyst exeresis and pelvic bone curettage with implant retention was performed. This case report demonstrates that hydatid cysts should be considered as a possible cause for non-specific pelvic pain, especially in endemic locations.     

Reproductive factors and the risk of scleroderma: An Italian case–control study

Objective

To investigate the association between scleroderma (systemic sclerosis; SSc) and reproductive factors in a hospital‐based case–control study conducted at the University Hospital of Verona in Northeastern Italy.

Methods

Forty‐six confirmed cases of SSc in women (42 with diffuse SSc and 4 with limited SSc) and 153 female control subjects with orthopedic disorders were recruited at the University Hospital. For each subject, information on age at first pregnancy, number of children and abortions, and use of oral contraceptives was obtained by means of a structured questionnaire, and information on the subject's occupational history and lifestyle factors was also sought.

Results

Parous women had a reduced risk of SSc (age‐adjusted odds ratio [OR] 0.3, 95% confidence interval [95% CI] 0.1–0.8) compared with nulliparous women. The risk decreased with an increasing number of children: the age‐adjusted OR was 0.6 (95% CI 0.2–1.7) for those women who had had 1 child, 0.3 (95% CI 0.1–0.7) for those having had 2 children, and 0.3 (95% CI 0.1–0.8) for those having had 3 or more children. Abortive pregnancies were inversely related to SSc risk: for women who had an abortion, the OR was 0.5 (95% CI 0.2–1.5) compared with women with no history of abortion. The overall history of any pregnancy (abortive or age‐adjusted complete) was associated with a reduced risk of SSc (age‐adjusted OR 0.3, 95% CI 0.1–0.7).

Conclusion

Since the incidence of SSc is higher in women and has its peak after childbearing age, it has been hypothesized that immunobiologic modifications during pregnancy may be associated with SSc development. Our findings showing a reduced risk of SSc among parous women seem to exclude the possibility of pregnancy itself as a risk factor for SSc. The role of HLA compatibility between the mother and the fetus, however, should be evaluated in further research.

     

Diagnostic delay in autoimmune oral diseases

Autoimmune diseases (ADs) affect about 5% of the general population, causing various systemic and/or topical clinical manifestations. The oral mucosa is often affected, sometimes as the only involved site. The misdiagnosis of oral ADs is an underreported issue. This narrative review focuses on diagnostic delay (DD) in oral ADs (oral lichen planus [OLP], oral Pemphigus Vulgaris, mucous membrane pemphigoid, oral lupus erythematosus, orofacial granulomatosis, oral erythema multiforme [EM], and Sjogren syndrome). Extensive literature research was conducted via MEDLINE, Embase and Google Scholar databases for articles reporting the time spent to achieve the correct diagnosis of oral ADs. Only 16 studies reported DD in oral ADs. Oral autoimmune vesiculobullous diseases are usually diagnosed after 8 months from the initial signs/symptoms, the Sjogren Syndrome diagnosis usually requires about 73 months. No data exist about the DD in OLP, oral lupus erythematosus, orofacial granulomatosis, and oral EM. The diagnosis of oral ADs can be difficult due to the non-specificity of their manifestations and the unawareness of dentists, physicians, and dental and medical specialists about these diseases. This can lead to a professional DD and a consequential treatment delay. The delay can be attributed to the physicians or/and the healthcare system (Professional Delay) or the patient (Patient's Delay).