In recent years the hypothesis that gut microbiota associates with Parkinson's disease (PD) has gained importance, although it has not been possible to define a specific microbiota composition as a ...predictive biomarker of this disease. We have investigated dysbiosis of gut microbiota in a selected population of PD patients from Central Italy, and examined the weight of specific confounders and predictors, in order to identify potential correlations with clinical phenotypes.
152 fecal samples were collected from 80 patients and 72 healthy controls. Patients were enrolled according to tight inclusion criteria. Microbiota composition was studied through 16s ribosomal RNA gene amplicon sequencing analysis in combination with data on dietary/life habits. Age, loss of weight, and sex were recognized as confounding factors, whereas PD-status, age, Body Mass Index, “eat cereals”, “gain of weigth” and “physical activity” as predictors. The presence of Lactobacillaceae, Enterobacteriaceae and Enterococcaceae families was significantly higher in feces from PD patients compared to healthy controls, while Lachnospiraceae were significantly reduced. Lower levels of Lachnospiraceae and higher levels of Enterobacteriaceae families also correlated with increased disease severity and motor impairment (Hoehn & Yahr stage, MDS-UPDRS Part III). Predictive metagenomics indicated a significant variation of genes involved in the metabolism of short chain fatty acids and amino acids, and in lipopolysaccharide biosynthesis.
PD showed a distinctive microbiota composition. Functional predictions suggest changes in pathways favoring a pro-inflammatory environment in the gastrointestinal tract, and a reduction in the biosynthesis of amino acids acting as precursors of physiological transmitters.
•Gut microbiota composition is a predictor for PD patients.•Bacteria families involved in pro- and anti-inflammatory environment are altered between patients and healthy controls.•Lachnospiraceae and Enterobacteriaceae abundance are related with disease severity.
The purpose of this note is to show that a finitely generated graded module
M
over
S
=
k
x
1
,
…
,
x
n
,
k
a field, is sequentially Cohen-Macaulay if and only if its arithmetic degree
adeg
(
M
)
...agrees with
adeg
(
F
/
gin
revlex
(
U
)
)
, where
F
is a graded free
S
-module and
M
≅
F
/
U
. This answers positively a conjecture of Lu and Yu from 2016.
Let
R
be a polynomial ring over a field. We describe the extremal rays and the facets of the cone of local cohomology tables of finitely generated graded
R
-modules of dimension at most two. ...Moreover, we show that any point inside the cone can be written as a finite linear combination, with positive rational coefficients, of points belonging to the extremal rays of the cone. We also provide algorithms to obtain decompositions in terms of extremal points and facets.
Low frequency deep brain stimulation (DBS) of the pedunculopontine nucleus area (PPNa) has been proposed as a novel surgical target for gait dysfunction in the late stage of Parkinson's disease (PD). ...Since the mid-2000s, we have shown that intrasurgical delivery of stimulation in the pontine tegmentum affects the firing activity in the subthalamic nucleus (STN), but its effect on STN oscillatory rhythms has not been studied. Neuronal oscillations detected by local field potential (LFPs) have great importance, since they express complex movement-related behavior such as locomotion. Therefore, we examined the effect of three PPNa-DBS stimulation protocols (at 10, 25 and 80 Hz) on the STN oscillatory activity of PD patients. We focused on the anti-kinetic beta (β, 15–30 Hz), the pro-kinetic gamma (γ, 60–90 Hz) and “gait-related” alpha (α, 7–12 Hz) bands. We hypothesized that modulation of STN oscillations might have clinical relevance in the PPNa-mediated effects.
PPNa stimulation at 25 and 80 Hz decreased the power of the STN β band by 33.94 and 40.22%, respectively. PPNa-DBS did not affect the other two bands with a tendency to suppress α power, while γ oscillation increased.
Our results suggest that the anti-kinetic β band is the oscillation most sensitive to PPNa-DBS despite the negligible clinical efficacy on bradykinesia. However, how these changes interact reciprocally with the cortex or are counterbalanced by lower brainstem/spinal pathways remain to be elucidated.
Our observation might turn out to be helpful in new protocols designed with adaptive DBS supporting the addition of PPN implantation in PD patients experiencing declining efficacy of STN-DBS.
Inspired by methods in prime characteristic in commutative algebra, we introduce and study combinatorial invariants of seminormal monoids. We relate such numbers with the singularities and ...homological invariants of the semigroup ring associated to the monoid. Our results are characteristic independent.
Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced the recurrence rate and improved the overall survival (OS) of patients with Stage ...III and IV melanoma, only a percentage will benefit of durable disease control. The aim of this study was to examine whether the levels of circulating tumour DNA (ctDNA) in plasma of advanced melanoma patients undergoing BRAFi/MEKi or ICIs vary according to the patients' survival outcomes (i.e. progression-free survival (PFS) and OS) and disease progression. Plasma samples of Stage III-IV melanoma patients were collected at baseline (treatment initiation) and thereafter every 3 months. Circulating BRAF
and NRAS
mutations were analysed through droplet digital PCR (ddPCR, Bio-Rad) in a total of 177 plasma samples from 48 melanoma patients (19 Stage III, 29 Stage IV). Baseline ctDNA concentration was significantly associated with OS (HR = 1.003, 95% CI = 1.000-1.006, p = 0.043) and PFS (HR = 1.004, 95% CI = 1.000-1.007, p = 0.029) independent of clinical-prognostic confounders. For each unit increase in the ∆ctDNA (concentration difference between the last follow-up and baseline) there was a 24% increased risk of disease progression, irrespective of treatment type and stage at diagnosis (OR = 1.24, 95% CI = 1.03-1.49, p = 0.020, AUC = 0.93). Patients with reduction of ctDNA level from baseline to the last follow-up had longer OS (HR = 0.14; 95% CI = 0.05-0.44, p = 0.001) and PFS (HR = 0.08; 95% CI = 0.03-0.27, p < 0.0001) compared to patients with increased ctDNA, including adjustment for confounding factors. Our findings suggest that variation of ctDNA over time during melanoma treatment reflects the clinical outcome and tumour response to therapy and might be helpful in clinical monitoring.
The prevention of recurrence after a first episode of primary spontaneous pneumothorax (PSP) remains a debated issue. The likelihood of recurrence based on the presence of blebs and bullae detected ...on high-resolution computed tomography (HRCT) imaging is controversial.
We evaluated patients conservatively treated for PSP who underwent chest HRCT scan in a single-institution retrospective longitudinal study. Absolute risk values and positive and negative predictive values of recurrence based on HRCT findings were the primary end points.
We analyzed 176 patients. Ipsilateral and contralateral recurrence developed in 44.8% and 12% of patients, respectively. The risk of recurrence was significantly related to the presence of blebs or bullae, or both, at HRCT. The risk of ipsilateral recurrence for patients with or without blebs and bullae was 68.1% and 6.1%, respectively (positive predictive value, 68.1%; negative predictive value, 93.9%). The risk of contralateral pneumothorax for patients with or without blebs and bullae was 19% and 0%, respectively (positive predictive value, 19%; negative predictive value, 100%). The risk of ipsilateral recurrence was directly related to the dystrophic severity score: recurrence risk increased by up to 75% in patients with bilateral multiple lesions. Multivariate analysis showed that a positive HRCT was significantly related to ipsilateral recurrence.
The presence of blebs and bullae at HRCT after a first episode of PSP is significantly related to the development of an ipsilateral recurrence or a contralateral episode of pneumothorax. Further studies are needed to validate the dystrophic severity score in the selection of patients for early surgical referral.
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