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With more effective screening and treatment strategies, there is debate over whether surgical axillary staging should be deescalated for patients with small favorable breast cancers, such as tubular carcinoma (TC).<br /><br /> We identified patients with TC [defined as &gt; 90% tubular tubules (angulated, not multilayered)] and known surgical axillary staging from our institutional database (2000-2018). Using the National Cancer Database (NCDB) (2004-2015), we identified patients with TC, ductal carcinoma in situ (DCIS), and pT1 estrogen receptor (ER)-positive invasive ductal carcinoma (IDC). We determined the rates of lymph node (LN) metastases, and the 5- and 10-year overall survival (OS) for patients with LN-negative versus LN-positive disease using the Kaplan-Meier method and propensity match analysis.<br /><br /> In our institutional cohort, we identified 112 patients with T1 TC; only one (0.9%) patient had nodal involvement. In the NCDB cohort, we identified 6938 patients with T1 TC; 323 (4.7%) patients had axillary LN disease. The rate of axillary LN involvement for TC was comparable to that identified for patients with DCIS (4.2%), and much lower than that found for patients with grade I-III, T1, ER-positive IDC (20.5%), and patients with grade I, T1, ER-positive IDC (14.4%). There was no difference in 5-year (94.6% versus 95.4%, p = 0.67) and 10-year (83.9% versus 85.2%, p = 0.98) OS between TC patients with or without LN involvement. Kaplan-Meier survival curves even after propensity score matching suggest that tubular histology is independently associated with improved survival.<br /><br /> T1 TC is an excellent starting point for deescalation of surgical axillary staging.<br /><br />T1 TC is an excellent starting point for deescalation of surgical axillary staging.Many proteins are phosphorylated at more than one phosphorylation site to achieve precise tuning of protein function and/or integrate a multitude of signals into the activity of one protein. Increasing the number of phosphorylation sites significantly broadens the complexity of molecular mechanisms involved in processing multiple phosphorylation sites by one or more distinct kinases. The cardiac ryanodine receptor (RYR2) is a well-established multiple phospho-target of kinases activated in response to β-adrenergic stimulation because this Ca2+ channel is a critical component of Ca2+ handling machinery which is responsible for β-adrenergic enhancement of cardiac contractility. Our review presents a selective overview of the extensive, often conflicting, literature which focuses on identifying reliable lines of evidence to establish if multiple RYR2 phosphorylation is achieved randomly or in a specific sequence, and whether phosphorylation at individual sites is functionally specific and additive or similar and can therefore be substituted.<br /><br /> Fabry disease (FD) is an X-linked lysosomal storage disorder resulting in vascular glycosphingolipid accumulation and increased stroke risk. MRI findings associated with FD include white matter hyperintensities (WMH) and cerebral microbleeds (CMBs), suggesting the presence of cerebral small vessel disease. MRI-visible perivascular spaces (PVS) are another promising marker of small vessel disease associated with impaired interstitial fluid drainage. We investigated the association of PVS severity and anatomical distribution with FD.<br /><br /> We compared patients with genetically proven FD to healthy controls. PVS, WMH, lacunes and CMBs were rated on standardised sequences using validated criteria and scales, blinded to diagnosis. A trained observer (using a validated rating scale), quantified the total severity of PVS. We used logistic regression to investigate the association of severe PVS with FD.<br /><br /> We included 33 FD patients (median age 44, 44.1% male) and 20 healthy controls (median age 33.5, 50% male). Adjusting for age and sex, FD was associated with more severe basal ganglia PVS (odds ratio (OR) 5.80, 95% CI 1.03-32.7) and higher total PVS score (OR 4.03, 95% CI 1.36-11.89). Compared with controls, participants with FD had higher WMH volume (median 495.03mm<br /><br /> vs 0, p = 0.0008), more CMBs (21.21% vs none, p = 0.04), and a higher prevalence of lacunes (21.21% vs. 5%, p = 0.23).<br /><br /> PVS scores are more severe in FD than control subjects. Our findings have potential relevance for FD diagnosis and suggest that impaired interstitial fluid drainage might be a mechanism of white matter injury in FD.<br /><br />PVS scores are more severe in FD than control subjects. Our findings have potential relevance for FD diagnosis and suggest that impaired interstitial fluid drainage might be a mechanism of white matter injury in FD.<br /><br /> To explore the use of digital biomarkers to distinguish healthy controls (HC) from subjects with a radiologically isolated syndrome (RIS).<br /><br /> We developed a smartphone application called MS Screen Test (MSST) to explore several dimensions of the neurological exam such as finger tapping speed, agility, hand synchronization, low contrast vision and cognition during a short evaluation. This app was tested on a cohort of healthy volunteers including a subset of subjects who underwent two evaluations on the same day to assess reproducibility. In a second step, the app was tested on a cohort of RIS subjects. Performances of RIS subjects were compared with age and genre-matched HC.<br /><br /> HC underwent two consecutive evaluations on MSST. The analysis showed good reproducibility for all measures. Then 21 RIS subjects were compared to 32 matched HC. Compared to HC, we found that RIS subjects had a lower finger tapping speed on the dominant hand (5.6 versus 6.5 taps per second; p = 0.005), a longer inter hand interval during the hand synchronization task (14.4 versus 11.3ms; p = 0.03) and significantly poorer scores on the low contrast vision and cognition tests.<br /><br /> MSST only requires a smartphone to obtain digital biomarkers relative to several dimensions of the neurological examination. Our results highlighted subtle differences between HC and RIS subjects. We plan to evaluate this tool in MS patients, which will allow us to get a much larger sample of subjects, to determine whether digital biomarkers can predict disease course.<br /><br />MSST only requires a smartphone to obtain digital biomarkers relative to several dimensions of the neurological examination. Our results highlighted subtle differences between HC and RIS subjects. We plan to evaluate this tool in MS patients, which will allow us to get a much larger sample of subjects, to determine whether digital biomarkers can predict disease course.<br /><br /> To evaluate clinical response after external lumbar drainage (ELD) and ventriculoperitoneal shunting (VPS) in a cohort of patients with idiopathic normal pressure hydrocephalus associated with parkinsonism (iNPH-P), considering parkinsonism as clinical primary outcome.<br /><br /> Patients underwent long-term 72-h intracranial pressure-controlled CSF ELD. Clinical motor response before and after ELD was evaluated using changes in UPDRS-ME as outcome measure. A standardized cognitive assessment was also performed. iNPH-P patients who underwent VPS were clinically followed-up after surgery.<br /><br /> Fourteen iNPH-P patients (age 69.3 ± 11.6years) were studied. The time of evaluation after ELD removal was 3.5 ± 1.8days. We observed a significant motor improvement after the drainage in eight (57.1%) patients. Percent clinical motor response was 18.4 ± 6.7%. Twelve (85.7%) patients underwent VPS. [https://www.selleckchem.com/products/bay-2402234.html check details] Nine patients were examined after surgery at 31.6 ± 7months. Four (44.4%) patients presented a clinically detectable improvement in motor response after VPS. No significant changes in cognitive performances were detected.<br /><br /> A clinically detectable motor response on parkinsonian signs was observed in a consistent part of iNPH-P patients few days after ELD as well as over two and half years after VPS. Parkinsonism should be considered as outcome measure for the clinical management of patients with iNPH-P.<br /><br />A clinically detectable motor response on parkinsonian signs was observed in a consistent part of iNPH-P patients few days after ELD as well as over two and half years after VPS. Parkinsonism should be considered as outcome measure for the clinical management of patients with iNPH-P.This study was conducted to investigate the effects of hot-melt extrusion (HME)-processed copper (Cu) sulfate supplementation on the growth performance, gut microbiota, metabolic function of Cu, and bioavailability of Cu in weanling pigs fed a corn-soybean meal basal diets. A total of 180 piglets (Yorkshire × Landrace × Duroc) of mixed-sex randomly were allotted to six treatments on the basis of initial average body weight (6.36 ± 0.39 kg) to six dietary treatments. There were six replicates in each treatment with 5 pigs per replicates. The dietary treatments included levels of CuSO4 (IN6, 6 mg Cu/kg diets; IN125, 125 mg Cu/kg diets), nano-CuSO4 (HME6, 6 mg Cu/kg diets; HME65, 65 mg Cu/kg diets; and HME125, 125 mg Cu/kg diets), and Cu-methionine (ORG125, 125 mg Cu/kg diets). The weanling pigs fed diets supplemented with the HME65 and HME125 showed a greater body weight and feed intake compared with IN6 and IN125 (P  less then  0.05). The weaning pigs fed diets supplemented with the HME125 showed the highest datment (P  less then  0.05). Taken together, these results suggest that the HME65 can be an alternative to IN125 in weanling pigs due to the greater overall average daily gain, improved villus height, and higher bioavailability.Cadmium pollution is serious heavy metal pollution in environmental pollution and impacts on livestock productivity. However, the effect and mechanisms of cadmium toxicity on the broiler remain unclear. This study aimed to explore the liver oxidative damage and reveal the related long non-coding RNA (lncRNA) expression patterns in the broiler liver with cadmium exposure. The broilers were fed with diets containing CdCl2 and detected the oxidative stress indexes in the liver tissues. Transcriptome sequencing of broiler liver was performed to identify cadmium exposure-related differentially expressed lncRNAs (DElncRNAs). The functions and pathways of DElncRNAs were analyzed by GO and KEGG. The sequencing results were verified by the quantitative real-time polymerase chain reaction. Cadmium exposure induced tissue structure disorder, focal hemorrhage, and irregular hepatocytes in the broiler liver, and significantly decreased GSH level and enzyme activities, and increased MDA expression in the liver. A total of 74 DElncRNAs were obtained in cadmium group compared with the control group, which were enriched in the GO terms, including intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator, branched-chain amino acid biosynthetic process. The enriched KEGG pathways, including lysine biosynthesis, valine, leucine and isoleucine biosynthesis, and pantothenate and CoA biosynthesis, were related to oxidative stress. PCR analysis indicated that the changes in ENSGALG00000053559, ENSGALG00000053926, and ENSGALG00000054404 expression were consistent with sequencing. Our results provide novel lncRNAs involved in oxidative stress in the broiler liver with cadmium exposure.