Pharmacogenetics of tenofovir drug transporters in the context of HBV: Is there an impact?

BACKGROUND: Current treatments for chronic hepatitis B management include orally administered nucleos(t)ide analogues, such as tenofovir (TDF), which is an acyclic adenine nucleotide analogue used both in HBV and human immune deficiency virus (HIV). The course of HBV infection is mainly dependent on viral factors, such as HBV genotypes, immunological features and host genetic variables, but a few data are available in the context of HBV, in particular for polymorphisms of genes encoding proteins involved in drug metabolism and elimination. Consequently, the aim of this study was to evaluate the potential impact of genetic variants on TDF plasma and urine concentrations in patients with HBV, considering the role of HBV genotypes. METHODS: A retrospective cohort study at the Infectious Disease Unit of Amedeo di Savoia Hospital, Torino, Italy, was performed. Pharmacokinetic analyses were performed through liquidi chromatography, whereas pharmacogenetic analyses through real-time PCR. FINDINGS: Sixty - eight patients were analyzed: ABCC4 4976 C>T genetic variant showed an impact on urine TDF drug concentrations (p = 0.014). In addition, SLC22A6 453 AA was retained in the final regression multivariate model considering factors predicting plasma concentrations, while ABCC4 4976 TC/CC was the only predictor of urine concentrations in the univariate model. INTERPRETATION: In conclusion, this is the first study showing a potential impact of genetic variants on TDF plasma and urine concentrations in the HBV context, but further studies in different and larger cohorts of patients are required.

The role of preoperative prostatic shape in the recovery of urinary continence after robotic radical prostatectomy: a single cohort analysis.

BACKGROUND: To explore the role of preoperative MRI prostate shape in urinary incontinence after robot-assisted radical prostatectomy (RARP). METHODS: Patients were stratified into four groups based on the mpMRI prostatic apex shape: Group A (prostatic apex overlapping the membranous urethra anteriorly and posteriorly), Group B and C (overlap of the prostatic apex of the anterior or posterior membranous urethra, respectively) and Group D (no overlap). Preoperative variables and intraoperative data were compared. Continence recovery was defined as no pad/day or 1 safety pad/day by an outpatient evaluation performed at 1, 3, 6, and 12 months after RARP. RESULTS: One hundred patients underwent RARP were classified as belonging to Group A (n = 30), Group B (n = 16), Group C (n = 14), and Group D (n = 40). Group D showed a significantly more favorable urinary continence recovery after RARP respect to all the other shapes presenting any forms of overlapping (HR = 1.9, 95% CI 1.2-3.1, p = 0.007). The estimated HR remained substantially unchanged after adjusting by age, body mass index, CCI, prostate volume, and bladder neck sparing (HR = 1.9, 95% CI 1.1-3.2, p = 0.016). The continence recovery median time was 9 months for Group A + B + C (95% CI 5-11) and 4 months for Group D (95% CI 2-6) (p = 0.023). CONCLUSION: Shape D showed a better continence recovery when compared to other shapes presenting any kind of overlapping of the prostatic apex over the membranous urethra.

Standardization of retrograde intrarenal surgery with "gravity irrigation" technique leads to low postoperative infection rate regardless of surgeon experience

Objectives: We aimed to evaluate the prevalence and predictive factors of postoperative infections after a standardized low-pressure RIRS technique. The secondary outcome was comparing surgeons’ experience in terms of infective complication and stone-free rate. Methods: A single-center retrospective analysis was conducted on all patients who underwent RIRS for kidney stones between January 2018 and February 2019. Inclusion criteria: adults, stone ≤ 20 mm (unless percutaneous nephrolithotomy contraindica-tions). Concomitant ureteral lithotripsy was allowed. Exclusion criteria: bilateral surgery, active urinary tract infections (UTI), pregnancy, fever at surgery. Low-pressure RIRS and ureteroscopy was achieved with gravity irrigation, a 5 Ch open-ended urethral catheter (ureteral lithotripsy), intravenous furosemide (20 mg), and ureteral access sheath above the ureteral-pelvic junction (RIRS). Results: 236 patients were included in the analysis. Mean age was 55.89±13.96 years. Mean stone diameter was 14.28±5.81mm. 43 (18.2%) patients underwent concomitant ureteral lithotripsy. Mean operative time was 61.10 ± 31.36 minutes. Infective complications occurred in 13 (5.5%) patients. Sepsis occurred in 10 (4.2%) patients and septic shock occurred in 1 (0.4%). One patient (0.4%) required stent substitution. Multivariate logistic regression analysis showed that history of UTI predicted for higher risk of postoperative infections (OR 8.434, CI 95% 2.36–29.46). Outcomes comparison of surgical expertise did not statistically differ in terms of stone-free rate and infective complications. Conclusion: Our standardized RIRS technique achieved a low postoperative infective complication rate. History of UTI was the strongest predictor of postoperative infections (AU)

El impacto de la COVID-19 en las admisiones al servicio de urgencias, hospitalizaciones y manejo clínico de la urolitiasis en el centro de Italia: análisis multicéntrico / The impact of COVID-19 outbreak on urolithiasis emergency department admissions, hospitalizations and clinical management in central Italy: a multicentric analysis

INTRODUCCIÓN Y OBJETIVOS: Nuestro objetivo fue evaluar el impacto de la enfermedad del coronavirus de 2019 (COVID-19) en los ingresos en los servicios de urgencias (SU), las hospitalizaciones y el manejo clínico de los pacientes con urolitiasis. PACIENTES Y MÉTODOS: Realizamos un análisis retrospectivo multicéntrico de las admisiones en los servicios de urgencias de tres departamentos de urología de gran volumen (uno directamente implicado en el tratamiento de los pacientes de COVID-19 y dos no implicados) en Roma (Italia) entre marzo y abril de 2020 y en el mismo período de 2019. Se realizó un análisis estadístico del número de admisiones por urolitiasis, la tasa de complicaciones, hospitalización y el tipo de tratamiento recibido. RESULTADOS: Fueron incluidos 304 pacientes en el análisis. Se observó una reducción significativa en el número global de pacientes ingresados en urgencias por urolitiasis entre 2019 y 2020 (48,8%). Además, con respecto a la elección del tratamiento de los pacientes hospitalizados, se informó un aumento estadísticamente significativo de los procedimientos de extracción de cálculos en comparación con el drenaje urinario en 2020 (p = 0,015). CONCLUSIONES: Durante la pandemia de la COVID-19 en Roma ha habido una reducción significativa de los ingresos en urgencias por urolitiasis. Los pacientes ingresados en el SU tuvieron más complicaciones, necesitaron hospitalización con más frecuencia y en cuanto al manejo clínico, se prefirió la extracción temprana de los cálculos, en vez del drenaje urinario. Todos los urólogos deben ser conscientes de que en los próximos meses podrían enfrentar un mayor número de admisiones por urolitiasis y un manejo de casos más complicados

INTRODUCTION AND OBJECTIVES: We aimed to evaluate how the corona virus disease of 2019 (COVID-19) outbreak influenced emergency department (ED) admissions for urolithiasis, hospitalizations and clinical management of the hospitalized patients. PATIENTS AND METHODS: We conducted a multicentric retrospective analysis of ED admissions in three high volume urology departments (one directly involved in COVID-19 patients management and two not involved) in Rome - Italy between March and April 2020 and in the same period of 2019. Statistical analysis was conducted on the number of admissions for urolithiasis, rate of complications, hospitalization and the type of treatment received. RESULTS. 304 patients were included in the analysis. A significant reduction in the global number of patients admitted to ED for urolithiasis between 2019 and 2020 (48.8%) was noted. Moreover, regarding the choice of treatment of hospitalized patients, a statistically significant increase of stone removal procedures versus urinary drainage was reported in 2020 (p = 0.015). CONCLUSIONS: During the COVID-19 pandemic in Rome there has been a significant reduction of emergency admissions for urolithiasis. Patients admitted to ED had more complications, more frequently need hospitalization and regarding clinical management early stone removal was preferred over urinary drainage only. All the urologists should be aware that in the next months they could face an increased number of admissions for urolithiasis and manage more complicated cases

The impact of COVID-19 outbreak on urolithiasis emergency department admissions, hospitalizations and clinical management in central Italy: a multicentric analysis. / El impacto de la COVID-19 en las admisiones al servicio de urgencias, hospitalizaciones y manejo clínico de la urolitiasis en el centro de Italia: análisis multicéntrico.

INTRODUCTION AND OBJECTIVES: We aimed to evaluate how the corona virus disease of 2019 (COVID-19) outbreak influenced emergency department (ED) admissions for urolithiasis, hospitalizations and clinical management of the hospitalized patients. PATIENTS AND METHODS: We conducted a multicentric retrospective analysis of ED admissions in three high volume urology departments (one directly involved in COVID-19 patients management and two not involved) in Rome - Italy between March and April 2020 and in the same period of 2019. Statistical analysis was conducted on the number of admissions for urolithiasis, rate of complications, hospitalization and the type of treatment received. RESULTS: 304 patients were included in the analysis. A significant reduction in the global number of patients admitted to ED for urolithiasis between 2019 and 2020 (48.8%) was noted. Moreover, regarding the choice of treatment of hospitalized patients, a statistically significant increase of stone removal procedures versus urinary drainage was reported in 2020 (p = 0.015). CONCLUSIONS: During the COVID-19 pandemic in Rome there has been a significant reduction of emergency admissions for urolithiasis. Patients admitted to ED had more complications, more frequently need hospitalization and regarding clinical management early stone removal was preferred over urinary drainage only. All the urologists should be aware that in the next months they could face an increased number of admissions for urolithiasis and manage more complicated cases.

Heat shock influences the fatty acid composition of the muscle of the Antarctic fish Trematomus bernacchii.

In the Ross Sea region (average temperature of -1.87 °C), shelf water warming up to +0.8-+1.4 °C is predicted by 2200, so there is an urgent need to understand how organisms can respond to rising temperatures. In this study, we analyzed the effect of a heat shock on the fatty acid (FAs) composition of muscle of the Antarctic teleost Trematomus bernacchii, caught in Terra Nova Bay (Ross Sea), and held in fish tanks at 0, +1 or +2 °C, for 1, 5 and 10 days. In general, heat shock produced, beyond a reduction in total lipid content correlated to the temperature, an increase in the percentage of saturated FAs, and a decrease in mono-unsaturated FAs; however, the level of poly-unsaturated FAs did not seem to directly correlate with temperature. Principal component analysis indicated that both temperature and exposure time affect the composition of FAs in the muscle probably through an alteration of the metabolic pathways of FAs. In this study, we demonstrated that T. bernacchii was capable to rapidly acclimatize to a heat shock. This study contributes to increasing knowledge on the effect of temperature on the lipid composition of T. bernacchii and is complementary to previous studies on the gene expression and biochemistry of this species face multiple stressors.

A multidisciplinary approach to study the reproductive biology of wild prawns.

This work aims to provide deeper knowledge on reproductive biology of P. kerathurus in a multidisciplinary way. Upon 789 examined females, 285 were found inseminated. The logistic equation enabled to estimate the size at first maturity at 30.7 mm CL for female. The Gono-Somatic Index (GSI) showed a pronounced seasonality, ranged from 0.80 ± 0.34 to 11.24 ± 5.72. Histological analysis highlighted five stages of ovarian development. Gonadal fatty acids analysis performed with gas chromatograph evidenced a pronounced seasonal variation; total lipids varied from 1.7% dry weight (dw) in Winter, to 7.2% dw in Summer. For the first time, a chemometric approach (Principal Component Analysis) was applied to relate GSI with total lipid content and fatty acid composition of gonads. The first two components (PC1 and PC2) showed that seasonality explained about 84% of the variability of all data set. In particular, in the period February-May, lipids were characterized by high PUFAs content, that were probably utilized during embryogenesis as energy source and as constituent of the cell membranes. During the summer season, gonads accumulated saturated FAs, that will be used during embryogenesis and early larval stages, while in the cold season total lipids decreased drastically and the gonad reached a quiescent state.

Distribution of Cd, Pb and Cu between dissolved fraction, inorganic particulate and phytoplankton in seawater of Terra Nova Bay (Ross Sea, Antarctica) during austral summer 2011-12.

During the austral summer 2011-2012, the metal quotas of Cd, Pb and Cu in the phytoplankton of Terra Nova Bay (TNB, Antarctica) were measured for the first time. Evolution of all the three metal distributions between dissolved and particulate fractions during the season was also evaluated. Metal concentrations were mainly affected by the dynamic of the pack ice melting and phytoplankton activity. In mid-December when TNB area was covered by a thick pack ice layer and phytoplankton activity was very low, all the three metals were present mainly in their dissolved species. When the pack ice started to melt and the water column characteristics became ideal (i.e. moderate stratification, ice free area), the phytoplankton bloom occurred. Cd showed a nutrient-type behaviour with dissolved and particulate fractions mainly influenced by phytoplankton activity. Cd quota showed a mean value of 0.12 ± 0.07 nmol L-1 (30-100% of the total particulate). Also Cu showed a nutrient-type behaviour, with its quota in phytoplankton varying between 0.08 and 2.1 nmol L-1 (20-100% of the total particulate). Pb features the typical distribution of a scavenged element with very low algal content (0.03 ± 0.02 nmol L-1, representing 20-50% of the total particulate). The vertical distribution of this element was influenced by several factors (e.g. pack ice melting, atmospheric inputs), the phytoplankton activity affecting Pb behaviour only partially. Metal:C ratios provide valuable information on the biological requirements for Cd, Pb and Cu, leading us to better understand their biogeochemical cycles.

Quantification of fatty acids in the muscle of Antarctic fish Trematomus bernacchii by gas chromatography-mass spectrometry: Optimization of the analytical methodology.

This work presents data on the quantification of fatty acids (FAs, in terms of mass unit per tissue weight) in the muscle of Trematomus bernacchii, a key species in Antarctica, often used as bioindicator for contamination studies. Modifications in fatty acids content should be considered a useful biomarker to study how contaminants affect Antarctic biota. Until now, very few studies quantified fatty acids of muscle of T. bernacchii, and only as percentage of a single fatty acid on total lipids. To perform the quantification of fatty acids, we used an analytical method based on a fast microwave-assisted extraction of lipids from a lyophilized sample, a base-catalyzed trans-esterification of lipid extract to obtain Fatty Acids Methyl Esters (FAMEs), and a separation and identification of FAMEs by gas chromatography-mass spectrometry. With the optimized and validated method, a fast and accurate separation of Fatty Acids Methyl Esters was performed in 43 min. The linearity was checked up to about 320 µg mL-1; limit of detection and limit of quantification are in the range 4-22 µg mL-1 and 13-66 µg mL-1, respectively. The optimized method showed a good accuracy and precision. Major fatty acids were 14:0, 16:0, 16:1n7, 18:1n9, 18:1n7, 20:1n9, 20:5n3 and 22:6n3. Quantified FAs compute for about 47 mg g-1 tissue dry weight (dw), with 9.1 ± 0.1 mg g-1 dw of saturated FAs, 25.5 ± 0.1 mg g-1 dw of mono-unsaturated FAs, and 12.2 ± 0.1 mg g-1 dw of poly-unsaturated FAs.

Diffusion-weighted imaging with dual-echo echo-planar imaging for better sensitivity to acute stroke.

BACKGROUND AND PURPOSE: Parallel imaging facilitates the acquisition of echo-planar images with a reduced TE, enabling the incorporation of an additional image at a later TE. Here we investigated the use of a parallel imaging-enhanced dual-echo EPI sequence to improve lesion conspicuity in diffusion-weighted imaging. MATERIALS AND METHODS: Parallel imaging-enhanced dual-echo DWI data were acquired in 50 consecutive patients suspected of stroke at 1.5T. The dual-echo acquisition included 2 EPI for 1 diffusion-preparation period (echo 1 [TE = 48 ms] and echo 2 [TE = 105 ms]). Three neuroradiologists independently reviewed the 2 echoes by using the routine DWI of our institution as a reference. Images were graded on lesion conspicuity, diagnostic confidence, and image quality. The apparent diffusion coefficient map from echo 1 was used to validate the presence of acute infarction. Relaxivity maps calculated from the 2 echoes were evaluated for potential complementary information. RESULTS: Echo 1 and 2 DWIs were rated as better than the reference DWI. While echo 1 had better image quality overall, echo 2 was unanimously favored over both echo 1 and the reference DWI for its high sensitivity in detecting acute infarcts. CONCLUSIONS: Parallel imaging-enhanced dual-echo diffusion-weighted EPI is a useful method for evaluating lesions with reduced diffusivity. The long TE of echo 2 produced DWIs that exhibited superior lesion conspicuity compared with images acquired at a shorter TE. Echo 1 provided higher SNR ADC maps for specificity to acute infarction. The relaxivity maps may serve to complement information regarding blood products and mineralization.

Bioactives and nutraceutical phytochemicals naturally occurring in virgin olive oil. The case study of the Nocellara del Belice Italian olive cultivar.

This work reports on the composition and bionutritional value of organic virgin olive oil from the Nocellara del Belice variety, one cultivated in the olive areas of the Sicily region, Italy. Destoned oils obtained by processing olives with a destoning-based procedure were compared with conventional oils. This innovative technique, consisting in removing the stone from fruits prior to processing, strongly enhanced the already high-quality level of the conventional product. An in-depth analytical investigation from 2008 to 2010 showed how this innovative olive extraction process led to an excellent peculiar final product, mainly attributable to the improved biophenol and volatile composition, as well as higher concentrations of the lipophilic and vitamin antioxidants (tocopherols and tocotrienols). It had higher levels of oleocanthal (p-HPEA-EDA), a nutraceutical compound exerting actions against COX1 and COX2 (cycloxygenases). Its head-space aroma displayed new volatile phytomolecules and also had higher levels of green volatiles from the lipoxygenase (LOX)-pathway (one having as precursors the polyunsaturated fatty acids containing a cis-cis-1,4-pentadiene system). Among the other bioactives, we highlight its significant levels of trans-ß-carotene and xanthophylls (lutein, violaxanthin, neoxanthin and other carotenoids). Its enhanced nutritional value was also attributable to the increased intensity of valuable tasting notes.

New insight into transient contrast enhancement on computed tomography after endovascular treatment of stroke.

Transient contrast enhancement on computed tomography following endovascular treatment of stroke is a recognized entity that has been previously reported. Technological advances in brain imaging now have the potential to explore and refine its proposed etiology. We describe three patients in whom the location of contrast enhancement correlates with decreased cerebral blood volume on pre-therapeutic CT perfusion studies and with restricted diffusion on MRI. In this regard, contrast enhancement demarcated areas of completed cerebral infarction. The diagnostic and etiological implications are discussed.

Enabling two adolescents with multiple disabilities to choose among environmental stimuli through different procedural and technological approaches.

Two single-case studies were carried out using different procedural and technological approaches to enable two adolescents with multiple disabilities to choose among environmental stimuli. Study I focused on replicating a recently developed procedure, which relied on samples of the auditory stimuli available as cues for choice responses. Study II assessed a new procedural and technical setup relying on the use of pictorial representations of the stimuli available as cues for choice responses. The auditory samples and the pictorial representations were presented through computer systems. The participants' choice responses relied on microswitches connected to the computer systems. The data of Study I fully supported previous findings with the same procedural approach. The participant learned to choose preferred stimuli and bypass nonpreferred ones. The data of Study II showed that the participant learned to concentrate his choice. responses on a few stimuli, suggesting that these stimuli were actually preferred and that responding was purposeful. Implications of the results were discussed.

Enabling a man with multiple disabilities and limited motor behavior to perform a functional task with help of microswitch technology.

This study evaluated the extent to which two microswitches used as interfaces would enable a man with multiple disabilities and limited motor behavior to operate an electric door opener at the entrance of the day center that he attended. Analysis showed the man (a) learned to use the two microswitches, (b) preferred the microswitch placed at his wheelchair's footrest (which also allowed more effective responding) over the microswitch placed at his wheelchair's armrest, and (c) maintained his positive performance at the 1- and 2-mo. postintervention checks. The results were discussed from a technical and practical standpoint and in terms of implications for the quality of life of persons with disabilities.

Writing program with word prediction for a young man with multiple disabilities: a preliminary assessment.

This study assessed a writing program with word prediction, which completed the writing of a word and spoke it out only when there was certainty that such a word was the correct one. The assessment was carried out with a young man with multiple disabilities, who typically used a word-processing program without word prediction. The two programs were compared on the time required by the participant for writing general sentences, through a social validation assessment, and eventually a check on the participant's preference. Analysis showed the program with word prediction was significantly more effective in terms of the writing time, which was halved, and was deemed preferable by 40 raters (psychology students) involved in the social validation assessment and by the participant himself. Implications of the findings are discussed.