Alzheimer’s disease (AD) is a multifactorial disease, implying that multi-target treatments may be necessary to effectively cure AD. Tetrahydrobiopterin (BH4) is an enzymatic cofactor required for the synthesis of monoamines and nitric oxide that also exerts antioxidant and anti-inflammatory effects. Despite its crucial role in the CNS, the potential of BH4 as a treatment in AD has never been scrutinized.

Here, we investigated whether BH4 peripheral administration improves cognitive symptoms and AD neuropathology in the triple-transgenic mouse model of AD (3xTg-AD), a model of age-related tau and amyloid-β (Aβ) neuropathologies associated with behavior impairment.

Non-transgenic (NonTg) and 3xTg-AD mice were subjected to a control diet (5% fat – CD) or to a high-fat diet (35% fat – HFD) from 6 to 13 months to exacerbate metabolic disorders. Then, mice received either BH4 (15 mg/kg/day, i.p.) or vehicle for ten consecutive days.

This sub-chronic administration of BH4 rescued memory impairment in 13-month-old 3xTg-AD mice, as determined using the novel object recognition test. Moreover, the HFD-induced glucose intolerance was completely reversed by the BH4 treatment in 3xTg-AD mice. However, the HFD or BH4 treatment had no significant impact on Aβ and tau neuropathologies.

Overall, our data suggest a potential benefit from BH4 administration against AD cognitive and metabolic deficits accentuated by HFD consumption in 3xTg-AD mice, without altering classical neuropathology. Therefore, BH4 should be considered as a candidate for drug repurposing, at least in subtypes of cognitively impaired patients experiencing metabolic disorders.

Overall, our data suggest a potential benefit from BH4 administration against AD cognitive and metabolic deficits accentuated by HFD consumption in 3xTg-AD mice, without altering classical neuropathology. Therefore, BH4 should be considered as a candidate for drug repurposing, at least in subtypes of cognitively impaired patients experiencing metabolic disorders.

Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer’s continuum in the 2018 NIA-AA research framework.

This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus.

From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAβ+) and amyloidnegative SCD (SCDβ-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences witated to amyloid-β load, highlighting incipient pathology in stage 2 of the AD continuum.

The aim of this study was to evaluate clinical features associated with benign histopathology of Prostate Imaging Reporting and Data System (PI-RADS) category 4 and 5 lesions.

Between March 2015 and November 2020, 1161 patients underwent mpMRI/Ultrasound-fusion-guided prostate biopsy (FBx) and concurrent 12-core systematic prostate biopsy (SBx) at the Department of Urology of the Ludwig-Maximilians-University of Munich, Germany. 848/ 1161 (73%) patients presented with either PI-RADS 4 or 5 index lesion and were retrospectively evaluated. Multivariate analysis was performed to evaluate clinical parameters associated with a negative outcome of PI-RADS 4 or 5 category lesions after FBx. Area under the receiver operating characteristics (ROC) curve (AUC) was conducted using ROC-analysis.

676/848 (79.7%) patients with either PI-RADS 4 or 5 index lesion were diagnosed with prostate cancer (PCa) by FBx and 172/848 (20.3%) patients had a negative biopsy (including the concurrent systematic prostate biopsy), resse features into daily clinical routine could be used for risk-stratification of these patients after negative biopsy of PI-RADS 4 or 5 index lesions.

Lesions with high or highly likelihood of PCa on multiparametric magnetic resonance imaging (mpMRI) but subsequent negative prostate biopsy occur in a small amount of patients. Localization of the lesion in the transitional zone, prostate volume and prebiopsy were shown to be predictors for benign histopathology of category 4 or 5 lesions on mpMRI. Integration of these features into daily clinical routine could be used for risk-stratification of these patients after negative biopsy of PI-RADS 4 or 5 index lesions.

To investigate the diagnostic value of core-needle biopsy (CNB) guided by contrast-enhanced ultrasound (CEUS) in cervical tuberculous lymphadenitis (CTL).

178 patients with pathological confirmation of CTL were retrospectively enrolled. All of them had undergone CNB prior to the final surgery. According to the different ways of puncture guidance, they were divided into two groups conventional ultrasound (US) group (n = 81) and CEUS group (n = 97). learn more The comparison of diagnostic efficacy between two groups was compared and analyzed.

Among the 178 patients, 146 were directly diagnosed as CTL by CNB, including 59 patients in CEUS group and 87 patients in US group. The diagnostic accuracy were 89.7% (87/97) and 72.8% (59/81), respectively (P <  0.01). For subgroup analyses, differences among diagnostic efficacy ascribed to the different guiding methods were significant in medium size group (>2.0 cm and ≤3.0 cm) and large size group (>3.0 cm), 91.7% for CEUS group vs. 69.0% for US group (P <  0.05) and 84.4% for CEUS group vs. 57.7% for US group (P <  0.05), respectively.

In the diagnosis of CTL, compared with the US-guided CNB, CEUS-guided CNB have certain advantages, especially for larger lymph nodes.

In the diagnosis of CTL, compared with the US-guided CNB, CEUS-guided CNB have certain advantages, especially for larger lymph nodes.