•Hexagonal and square lattices under steady-state, fully developed conditions.•Axial flow: fz and Sh increase by 26% and 79% in the hexagonal lattice.•Transverse flow: fT increases by 10-36% in the ...hexagonal lattice; similar Sh values.•Mixed flow: fT unaffected by axial flow; fz increased at transverse Re>~5-10.•Sh is the larger between that of purely transverse flow and purely axial flow.
Numerical simulations were conducted for fully developed, steady-state flow with mass transfer in fiber bundles arranged in regular lattices. The porosity was 0.5 and the Schmidt number 500. Several combinations of axial flow, transverse flow and flow attack angles in the cross-section plane were considered. The axial and transverse Reynolds numbers Rez, ReT were made to vary from 10−4 to 102. Concentration boundary conditions, and the definition of an average Sherwood number, were addressed. Results for the hydraulic permeability were compared with the literature. Both hexagonal and square lattices were found to be hydraulically almost isotropic up to transverse flow Reynolds numbers ReT of ~10, while they behaved anisotropically in regard to mass transfer even at ReT as low as 0.1. A larger anisotropy was exhibited by the square lattice. In mixed (axial+transverse) flow, the transverse friction coefficient was almost completely unaffected by the simultaneous presence of axial flow, while the axial friction coefficient (and thus the axial pressure loss) increased with the transverse Reynolds number for ReT>~5-10. In regard to mass transfer, the Sherwood number settled in all cases to the higher between the Sherwood number in purely transverse flow and that in purely axial flow.
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It is well-known that 75% of risk factors of chronic liver disease (CLD) are related to nutrition. These circumstances potentially progress towards liver steatosis, fibrosis and hepatocellular ...carcinoma (HCC). It still represents an enormous problem for the economy of public health worldwide. Furthermore, validated prevention programs could be the solution. Recent knowledge in understanding molecular determinants of energy liver metabolism and new genetic markers offers new insights into the pathogenesis of CLD and HCC. The main rationale of the present issue is to provide a summary of recent insights into the inherited variants regulating lipid metabolism (steatohepatitis) and acquired mutation for early diagnosis of HCC, specifically focusing on the significance of antioxidant agents and genotyping tests as a cost-effectiveness tool for the prevention of liver disease. Several national healthy programs worldwide promote the daily use of antioxidant nutrients either for the prevention and/or as complementary and alternative medicines (CAM). This review could be advising for the planning of a large-scale clinical trial including a combination strategy of antioxidant agents and genotyping tests in patients with high risk of CLD.
Here, we describe an atypical presentation of the rare R377W PSEN1 mutation, emphasizing the unusual late age of onset and the mixed frontotemporal and parieto‐hippocampal dysfunction. In order to do ...so, beside a detailed clinical characterization, we provide a description of the family tree, conventional imaging findings and, for the first time, amyloid‐PET. Extensive genetic screening is advisable also for late‐onset presentations of Alzheimer’s disease, especially in the presence of a positive family history or atypical clinical features.
Background and purpose
Mutations in the PSEN1 gene are the most common cause of autosomal‐dominant Alzheimer’s disease and have been associated with the earliest disease onset. We describe an unusual presentation of the rare R377W PSEN1 mutation with a late age of onset, and we provide for the first time in vivo pathological evidence for this mutation.
Methods
A 71‐year‐old female patient with progressive cognitive decline in the past 3 years and positive family history for dementia underwent neurological evaluation, neuropsychological testing, lumbar puncture, conventional brain imaging, amyloid‐positron emission tomography (PET) and extensive genetic screening with a next‐generation sequencing technique.
Results
The diagnostic workup revealed mixed behavioural and amnestic disease features on neuropsychological tests, magnetic resonance imaging, and 18‐fluorodeoxyglucose (FDG)‐PET. Amyloid‐PET detected amyloid deposition in the frontal areas, in the parietal lobes and the precunei. The genetic screening revealed the presence of the rare R377W mutation in the PSEN1 gene.
Conclusions
Extensive genetic screening is also advisable for late‐onset presentations of Alzheimer’s disease, especially in the presence of a positive family history or atypical clinical features.
Pulmonary interstitial emphysema (PIE) is a severe complication of mechanical ventilation in preterm infants. Selective bronchial intubation is a rarely used treatment strategy, as it is challenging, ...especially left main stem bronchial intubation. We report our experience in an infant at 24 weeks gestation with bedside left main stem bronchial intubation using flexible fiberoptic bronchoscopy. We also describe in detail the procedural details involved in the selective left main stem bronchial intubation including the helpful technique of gently bending the tip of the endotracheal tube to create "memory" to better direct the tube into the left main-stem bronchus while using the flexible fiberoptic bronchoscope. A review of the literature regarding selective bronchial intubation in newborn infants is presented. This case report and literature review suggest that bedside left main stem bronchial intubation using a flexible fiberoptic bronchoscope is a viable option to successfully manage even the most unstable extreme premature infant with unilateral right lung cystic PIE. This may potentially prevent a rare but necessary invasive surgical procedure like lobectomy or even death.
Bipolar disorder (BD) may be characterized by the presence of psychotic symptoms and comorbid substance abuse. In this context, structural and metabolic dysfunctions have been reported in both BD ...with psychosis and addiction, separately. In this study, we aimed at identifying neural substrates differentiating psychotic BD, with or without substance abuse, versus substance-induced psychosis (SIP) by coupling, for the first time, magnetic resonance imaging (MRI) and positron emission tomography (PET).
Twenty-seven BD type I psychotic patients with (n=10) or without (n=17) substance abuse, 16 SIP patients and 54 healthy controls were enrolled in this study. 3T MRI and 18-FDG-PET scanning were acquired.
Gray matter (GM) volume and cerebral metabolism reductions in temporal cortices were observed in all patients compared to healthy controls. Moreover, a distinct pattern of fronto-limbic alterations were found in patients with substance abuse. Specifically, BD patients with substance abuse showed volume reductions in ventrolateral prefrontal cortex, anterior cingulate, insula and thalamus, whereas SIP patients in dorsolateral prefrontal cortex and posterior cingulate. Common alterations in cerebellum, parahippocampus and posterior cingulate were found in both BD with substance abuse and SIP. Finally, a unique pattern of GM volumes reduction, with concomitant increased of striatal metabolism, were observed in SIP patients.
These findings contribute to shed light on the identification of common and distinct neural markers associated with bipolar psychosis and substance abuse. Future longitudinal studies should explore the effect of single substances of abuse in patients at the first-episode of BD and substance-induced psychosis.
At present, several strategies for preventing neuromuscular pain in Type 2 Diabetes Mellitus (T2DM) have been investigated. Recently, findings on genetic variants associated with adverse events to ...statin-based therapy have been reported. The study aimed at measuring whether Pharmacogenomics (PGx) profile can affect neuromuscular pain in patients carrying T2DM and cardiovascular diseases. An extensive panel of 5 polymorphisms on 4 candidate genes, previously validated as significant markers related to Sulphonylureas and Glitinides (SU-G) plus Simvastatin neuromuscular toxicity, is herein analyzed and discussed.
We genotyped 76 T2DM patients carrying cardiovascular dyscrasia undergone anti-diabetic and anti-cholesterolemic polypharmacy. 35 subjects out of the total received concurrent SU-G and Statin-based therapy. Candidate variants consisted of drug transporters, such as Solute Carrier Organic 1B1 (SLCO1B1) Val174Ala ATP-binding cassette subfamily B member (ABCB1), subfamily C member 8 (ABCC8), and drug biotransformers of Cytochrome P450 Family (CYP) including CYP2C9*2 CYP2C9*3 CYP2C8*3, and CYP3A4*22. Moreover, we also focused on an early outline evaluation of the genotyping costs and benefits.
6 out of 35 patients treated with SU-G plus statins (17.1% experienced adverse neuropathy events). Pharmacogenomics analysis showed a lack of any correlation between candidate gene polymorphisms and toxicity, except for the SLCO1B1 T521C allele; 14.3% of patients had a high risk for grade >2 neuromuscular pain (Odds Ratio OR 2.61.95% CI 0.90-7.61, p=0.03).
The clinical polymorphism effectiveness outlined therein will be assured by diagnostic improvements suitable for driving treatment decisions. In light of our experimental results and literature data, the analysis of the SLCO1B1 T521C variant will allow clinicians to take advantage from a better treatment planned for their patients in order to minimize neuromuscular pain and maximize benefits.
Objective: Different prevention strategies towards Type II Diabetes Mellitus (T2DM) patients with neuromuscular pain have been assessed in several studies. Recent data reported the correlation ...between genotype and neuromuscular events in patients, carrying both T2DM and cardiovascular disease, who were administered with statins-based therapy. In light of this, the present study was planned to evaluate whether Pharmacogenomics (PGx) profile can affect neuromuscolar pain in patients carrying T2DM and cancer. For this purpose, we have taken into account a panel of 4 polymorphisms on 4 candidate genes, already known as important markers related to Platin derivate and Biguanides (Pt-B) and peripheral neurotoxicity as “Hand-Foot syndrome” (HFS). Patients and Methods: We genotyped 37 T2DM/cancer patients who underwent anti-diabetic and polypharmacy; 17 of them received concurrent platin derivates and biguanides therapy. Candidate variants were genes encoding drug transporters as ATP-binding cassette subfamily B member (ABCB1), subfamily C member 8 (ABCC8), and drug enzymes as Cytochrome P450 Family (CYP) including CYP2C8*3 and Glutathione S Transpherase P1 (GSTP1). An early evaluation of genotyping costs and benefits was also pointed out. Results: Of 17 patients treated with Pt-B, 12 (65.7%) had adverse peripheral neuropathy events and 5 of them had HFS. Pharmacogenomics analysis showed a lack of any correlation between candidate genes polymorphisms and HFS toxicity. The genotyping results revealed that 14.1% of patients experienced grade >2 neurotoxicity, but none of them developed HFS (Odds Ratio OR 12.5, 95% CI 1.32-118.47, p= 0.003). Conclusions: The pharmacogenomic panel considered in the present work may play a decisive role in improving patients’ treatments with both cancer and T2DM. Our experimental results support pharmacogenomics implementation, helping physicians in clinical decisions. Patients will be provided with a better treatment able to minimize neuromuscular pain and increase benefits, in term of both therapy efficacy and economy for national healthcare system.
Summary
Background
Extracorporeal photopheresis (ECP) has been used successfully to treat severe steroid‐refractory acute and chronic graft‐versus‐host disease (aGVHD, cGVHD) since the late 1990s.
...Objectives
To evaluate retrospectively the efficacy and safety of ECP in patients with aGVHD. We also assessed whether ECP may play a role in the prevention of cGVHD.
Patients and methods
Nine consecutive patients with allografts with aGVHD grade II–III, as defined by consensus criteria, and refractory to steroids, were treated with ECP. ECP was started at a median interval of 46·3 days (range 10–70) from aGVHD onset. Patients were treated initially on two consecutive days (one cycle) at 1‐week intervals until improvement and then every 2 weeks. Treatment was then tapered off individually. To evaluate statistical relationships with outcome after 30, 60 and 90 days of ECP, all clinical and historical variables of the patients before treatment were analysed.
Results
All patients survived and responded within 90 days. The average aGVHD score was 1·72 at aGVHD onset, 2·44 when ECP was started and then gradually declined to 0·44 on day 90. At the same time, the average dose of methylprednisolone declined from 2·22 mg kg−1 to 0·27 mg kg−1 (day 90), while the average dose of ciclosporin declined from 2·46 mg kg−1 to 0·77 mg kg−1 (day 90). Six of nine patients showed a complete skin response after 90 days of treatment. All patients with liver and gastrointestinal tract involvement had complete responses after 90 days, apart from one patient. All our patients developed cGVHD, seven of nine while still on maintenance regimen (6–13 months after haematopoietic stem cell transplantation, HSCT) and the other two patients after suspension of ECP (6 and 9 months after HSCT).
Conclusions
ECP is effective in patients with mild to moderate steroid‐refractory aGVHD (grade II–III). On the other hand, ECP did not prevent the development of cGVHD in our patients.
What's already known about this topic?
Extracorporeal photopheresis (ECP) has been used successfully to treat severe steroid‐refractory acute and chronic graft‐versus‐host disease (aGVHD, cGVHD) since the late 1990s.
What does this study add?
ECP is effective in patients with mild to moderate steroid‐refractory aGVHD (grade II–III). On the other hand, ECP did not prevent the development of cGVHD in our patients.
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