Cutaneous neuropathy in Parkinson’s disease: a window into brain pathology

The deposition of alpha-synuclein in the brain, the neuropathological hallmark of Parkinson’s disease (PD), follows a distinct anatomical and temporal sequence. This study aimed to characterize alpha-synuclein deposition in cutaneous nerves from patients with PD. We further strived to explore whether peripheral nerve involvement is intrinsic to PD and reflective of known features of brain pathology, which could render it a useful tool for pathogenetic studies and pre-mortem histological diagnosis of PD. We obtained skin biopsies from the distal and proximal leg, back and finger of 31 PD patients and 35 controls and quantified the colocalization of phosphorylated alpha-synuclein in somatosensory and autonomic nerve fibers and the pattern of loss of different subtypes of dermal fibers. Deposits of phosphorylated alpha-synuclein were identified in 16/31 PD patients but in 0/35 controls (p < 0.0001). Quantification of nerve fibers revealed two types of peripheral neurodegeneration in PD: (1) a length-dependent reduction of intraepidermal small nerve fibers (p < 0.05) and (2) a severe non-length-dependent reduction of substance P-immunoreactive intraepidermal nerve fibers (p < 0.0001). The latter coincided with a more pronounced proximal manifestation of alpha-synuclein pathology in the skin. The histological changes did not correlate with markers of levodopa toxicity such as vitamin B12 deficiency. Our findings suggest that loss of peripheral nerve fibers is an intrinsic feature of PD and that peripheral nerve changes may reflect the two types of central alpha-synuclein-related PD pathology, namely neuronal death and axonal degeneration. Detection of phosphorylated alpha-synuclein in dermal nerve fibers might be a useful diagnostic test for PD with high specificity but low sensitivity.     

The Depression Screener for Teenagers (DesTeen): A valid instrument for early detection of adolescent depression in mental health care

Objective

Diagnosis of comorbid depressive disorder is challenging, even in mental health care. Screening instruments could be economic tools in indicating depression. For the first time, the current study investigates the validity of the newly developed Depression Screener for Teenagers (DesTeen) and its abbreviated five-item form DesTeen-a in a mental health setting.

Methods

A total of 88 patients aged 13–16 years were recruited in institutions specialized in child and adolescent psychiatry, psychotherapy or psychosomatic medicine. DSM-IV-TR diagnoses of major depression or dysthymia based on a structured diagnostic interview served as the gold standard for validation.For assessing the criterion validity of the DesTeen and the DesTeen-a, areas under the receiver operating characteristic curve (AUC) were calculated. Specificity and sensitivity were computed for optimal cut-off scores according to the Youden Index.

Results

Point prevalence of depression was 27.3%. Diagnostic accuracy of the DesTeen was high (AUC = .94). Using a cut-off score of ≥18, sensitivity was .96 and specificity was .86. The DesTeen-a showed no loss in validity (AUC = .94). At a cut-off point of ≥6, sensitivity remained excellent (.96), while specificity was slightly lower (.80).

Limitations

The limited representativeness and the small sample size restrict the generalizability of the findings.

Conclusions

The DesTeen and its abbreviated version are valid instruments to screen for adolescent depression in mental health care. Since structured interviews to diagnose comorbid mental disorders are rarely applied, the DesTeen and the DesTeen-a can support mental health specialists in making the diagnostic process more efficient, thus facilitating effective treatment planning.     

Heteroresistance to Fosfomycin Is Predominant in Streptococcus pneumoniae and Depends on the murA1 Gene

Fosfomycin targets the first step of peptidoglycan biosynthesis in Streptococcus pneumoniae catalyzed by UDP-N-acetylglucosamine enolpyruvyltransferase (MurA1). We investigated whether heteroresistance to fosfomycin occurs in S. pneumoniae. We found that of 11 strains tested, all but 1 (Hungary^19A) displayed heteroresistance and that deletion of murA1 abolished heteroresistance. Hungary^19A differs from the other strains by a single amino acid substitution in MurA1 (Ala₃₆₄Thr). To test whether this substitution is responsible for the lack of heteroresistance, it was introduced into strain D39. The heteroresistance phenotype of strain D39 was not changed. Furthermore, no relevant structural differences between the MurA1 crystal structures of heteroresistant strain D39 and nonheteroresistant strain Hungary^19A were found. Our results reveal that heteroresistance to fosfomycin is the predominant phenotype of S. pneumoniae and that MurA1 is required for heteroresistance to fosfomycin but is not the only factor involved. The findings provide a caveat for any future use of fosfomycin in the treatment of pneumococcal infections.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine compared to a 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naive adults

Background

Streptococcus pneumoniae is a major cause of morbidity and mortality among adults 50 years of age and older in the United States. Pneumococcal conjugate vaccines are efficacious against pneumococcal disease in children and may also offer advantages in adults.

Methods

We performed a randomized, modified double-blind trial that compared a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in 831 pneumococcal vaccine naive adults 60–64 years of age. An additional group of 403 adults 50–59 years of age received open-label PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured at baseline, and at 1 month and 1 year after vaccination.

Results

In the randomized trial, the month 1 post-vaccination OPA geometric mean titers in the PCV13 group were statistically significantly higher than in the PPSV23 group for 8 of the 12 serotypes common to both vaccines and for serotype 6A, a serotype unique to PCV13, and were comparable for the other 4 common serotypes. The immune response to PCV13 was generally greater in adults 50–59 years of age compared to adults 60–64 years of age. OPA titers declined from 1 month to 1 year after PCV13 administration but remained higher than pre-vaccination baseline titers.

Conclusions

PCV13 induces a greater functional immune response than PPSV23 for the majority of serotypes covered by PCV13, suggesting that PCV13 could offer immunological advantages over PPSV23 for prevention of vaccine-type pneumococcal infection.     

Anticholinergic therapy: do the patients take the pills prescribed?

Purpose  

To evaluate how many patients with overactive bladder still take their prescribed medication at least 12 months later and to find out the reasons for discontinuation of the therapy.