Adult-onset leukodystrophies from respiratory chain disorders: do they exist?

Respiratory chain disorders (RCDs) have been included in the differential diagnosis of adult-onset leukodystrophies. Here, we first report a 32-year-old female with an atypical, adult-onset, non-syndromic RCD due to a mitochondrial DNA deletion and manifesting as complicated ataxia. A ‘leukodystrophic’ pattern was found on brain MRI, but it was neither isolated nor predominant because of the presence of overt basal ganglia and infratentorial lesions, which led us to the proper diagnosis. Subsequently, we evaluated our series of patients with RCDs in order to verify whether a ‘leukodystrophic’ pattern with little or no involvement of deep grey structures and brainstem may be found in adult-onset RCDs, as reported in children. Among 52 patients with adult-onset RCDs, no case with a ‘leukodystrophic’ pattern was found, apart from three cases with a classical phenotype of mitochondrial neurogastrointestinal encephalopathy. In addition, no case of RCDs was found among six cases of adult-onset leukodystrophy of unknown origin and at least one feature suggestive of mitochondrial disease. The review of the literature was in agreement with these findings. Thus, we provide evidence that, unlike in children, RCDs should not be included in the differential diagnosis of adult-onset leukodystrophies, except when there are additional MRI findings or clinical features which unequivocally point towards a mitochondrial disorder.     

Mouthwashes in the 21st century: a narrative review about active molecules and effectiveness on the periodontal outcomes

Introduction: Poor oral hygiene is a major risk factor for oral diseases. Regular home-based care is essential to maintain good oral hygiene. In particular, mouthrinses can support conventional tooth brushing in reducing accumulation of oral plaque.

Areas covered: The most common molecules contained in mouthrinses (chlorhexidine, essential oils, cetyl pyridinium chloride, triclosan, octeneidine, delmopinol, polyvinylpyrrolidone, hyaluronic acid, natural compounds) are discussed, together with relevant clinical and in vitro studies, focusing on their effects on periodontal health. Currently, chlorhexidine is the most efficacious compound, with both antiplaque and antibacterial activities. Similar results are reported for essential oils and cetyl pyridinium chloride, although with a somewhat reduced efficacy. Considering the adverse effects of chlorhexidine and its time-related characteristics, this molecule may best be indicated for acute/short-term use, while essential oils and cetyl pyridinium chloride may be appropriate for long-term, maintenance treatment.

Expert opinion: The literature has not clearly demonstrated which compound is the best for mouthrinses that combine good efficacy and acceptable side effects. Research should focus on substances with progressive antibacterial activity, prompting a gradual change in the composition of oral biofilm and mouthrinses that combine two or more molecules acting synergistically in the mouth.     

Do neuropsychiatric fluctuations temporally match motor fluctuations in Parkinson’s disease?

Neurological Sciences - In Parkinson’s disease (PD), non-motor fluctuations (NMFs), especially neuropsychiatric fluctuations, often coexist with motor fluctuations (MFs) but are often...     

Determination of 1-phenyl-2-propanone (P2P) by HS-GC/MS in a material sold as “wet amphetamine”

In this paper, we describe the approach to the characterization of an unusual material seized by the judicial authority, near Brescia City in Northern Italy. Usual analyses such as thin-layer chromatography, gas chromatography (GC)–flame ionization detection, and GC/mass spectrometry (MS) did not show the presence of drugs of abuse, in particular amphetamine-like compounds. The major solid component was identified as cornstarch; then taking into account the strong aromatic scent of the seized material; a preliminary experiment for volatile organic compounds was carried out by headspace (HS)-GC/MS. This analysis tentatively evidenced the presence of 1-phenyl-2-propanone (P2P), an amphetamine precursor. Therefore, we developed and optimized a new analytical method for determination of P2P in seized materials by HS-GC/MS. We also synthesized P2P, with the permission of the Ministry of Health, to have it as reference standard, because of its being illegal and the difficulty in obtaining it. This case had some analogies with the cases referred to as “wet amphetamine” by the judicial authority, in which amphetamines are sold mixed with P2P. The possible use of the material could be the production of tablets made of cornstarch with an aromatic scent similar to that of amphetamines to deceive consumers and to sell them as a drug of abuse.     

Hepatitis C virus and liver transplantation: where do we stand?

The hepatitis C virus (HCV) infects more than 180 million people globally, with increasing incidence, especially in developing countries. HCV infection frequently progresses to liver cirrhosis leading to liver transplantation or death, and HCV recurrence still constitutes a major challenge for the transplant team. Antiviral therapy is the only available instrument to slow down this process, although its actual impact on liver histology, in responders and nonresponders, is still controversial. We are now facing a “new era” of direct antiviral agents that is already changing the approach to HCV burden both in the pre‐ and in the post‐liver transplantation settings. Available data on sofosbuvir/ledipasvir and sofosbuvir/simeprevir in patients with decompensated cirrhosis sustain a SVR12 of 89% 1 , but one‐third of patients do not clinically improved. The sofosbuvir/ribavirin treatment in stable cirrhotic patients with HCC before liver transplantation is associated with 2% recurrence rate if liver transplantation is performed at least one month after undetectable HCV‐RNA is achieved. The treatment of recurrence with the new antiviral drugs is associated with a SVR that ranges between 60 and 90%. In this review, we have focused on the evolution of antiviral therapy for HCV recurrence from the “old” interferon‐based therapy to the “new” interferon‐free regimens, highlighting useful information to aid the transplant hepatologist in the clinical practice.     

Circulating SIRT1 Increases After Intragastric Balloon Fat Loss in Obese Patients

Background

Sirtuins (SIRTs), ubiquitous deacetylases, are main regulators of energy homeostasis and metabolism. SIRT1 has a positive impact on obesity, diabetes mellitus, liver steatosis, and other metabolic disorders. Lean subjects have higher expression of SIRT1 in the adipose tissue compared to obese. However, it is not known whether weight loss associates with changes in blood SIRT1. We evaluated the effect of weight loss on circulating SIRT1, metabolic parameters, and body composition.

Methods

Thirty-two obese subjects were studied before and 6 months after BioEnterics® Intragastric Balloon (BIB®) [22 patients, BMI 41.82?±?6.28 kg/m²] or hypocaloric diet [10 patients, BMI 38.95?±?6.90 kg/m²]. Plasma SIRT1, body composition, measures of metabolic syndrome (waist circumference, fasting plasma glucose, blood pressure, HDL cholesterol, triglycerides), and inflammation markers (ESR, CRP, fibrinogen) were recorded.

Results

SIRT1 levels showed a significant increase, together with a significant reduction of BMI, excess body weight, and total fat mass either after BIB or diet intervention. The percent excess body weight loss was 33.73?±?19.06 and 22.08?±?11.62 % after BIB and diet, respectively, a trend toward a metabolic and inflammatory amelioration was observed with both treatments. Negative correlation between SIRT1 and % fat mass (BIB, ρ?=??0.537, p?=?0.017; diet, ρ?=??0.638, p?=?0.047) was also seen.

Conclusions

The reduction of fat mass associates with increased plasma SIRT1 indicating that, besides tissue levels, circulating SIRT1 is stimulated by a negative caloric balance. The rise of plasma SIRT1 may represent a parameter associating with fat loss rather than weight lowering regardless of the weight reduction system method used.

     

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).     

Microvessel density in sinus augmentation procedures using anorganic bovine bone and autologous bone: 3 months results

PURPOSE: This study was an immunohistochemical evaluation of microvessel density (MVD) in sinus augmentation procedures with autologous bone and anorganic bone (Bio-Oss). MATERIALS AND METHODS: Twenty-four patients (14 men and 10 women - mean age of 48 years with a range from 34 to 53 years) participated in this study. All the patients presented a maxillary partial unilateral edentulism involving the premolar/molar areas, with a residual alveolar ridge height of about 4 to 5 mm. Twelve patients received sinus augmentation procedures with 100% autologous bone; 100% Bio-Oss was used in the other 12 patients. Endosseous implants were inserted after a mean period of 3 months. As control, the portions of preexisting subantral bone were used. The mean value of the MVD in control bone was 23.4 +/- 1.3. The mean value of the MVD in the sinuses augmented with autologous bone was 29.0 +/- 2.4. The mean value of the MVD in the sinuses augmented with Bio-Oss was 23.8 +/- 2.2. RESULTS: The statistical analysis showed that the differences of the MVD between control bone and sinuses augmented with Bio-Oss were not statistically significant (P = 0.52), while the difference of the MVD between sinuses augmented with autologous bone and those augmented with Bio-Oss was statistically significant (P = 0.0008). CONCLUSIONS: Autologous bone may act not only as a passive filling material in bone defects but may also release osteogenic growth factors; and particles of autologous bone seem to contain vital osteoprogenitor cells.