Antarctic aldehyde dehydrogenase from Flavobacterium PL002 as a potent catalyst for acetaldehyde determination in wine.

Latest solutions in biotechnologies and biosensing targeted cold-active extremozymes. Analysis of acetaldehyde as a relevant quality indicator of wine is one example of application that could benefit from using low-temperatures operating catalysts. In search of novel aldehyde dehydrogenases (ALDH) with high stability and activity at low temperatures, the recombinant S2-ALDH from the Antarctic Flavobacterium PL002 was obtained by cloning and expression in Escherichia coli BL21(DE3). Structural and phylogenetic analyses revealed strong protein similarities (95%) with psychrophilic homologs, conserved active residues and structural elements conferring enzyme flexibility. Arrhenius plot revealed a conformational shift at 30 °C, favoring catalysis (low activation energy) at lower temperatures. In addition to a broad substrate specificity with preference for acetaldehyde (Km = 1.88 mM), this enzyme showed a high tolerance for ethanol (15%) and several salts and chelators (an advantage for wine analysis), while being sensitive to mercury (I50 = 1.21 µM). The neutral optimal pH (7.5) and the stability up to 40 °C and after lyophilization represent major assets for developing S2-ALDH-based sensors. An enzymatic electrochemical assay was developed for acetaldehyde detection in wines with proven accuracy in comparison with the reference spectrophotometric method, thus evidencing the potential of S2-ALDH as effective biocatalyst for industry and biosensing.

Electronic Medication Record Accuracy in Haemodialysis Outpatient Settings.

Aims Irish haemodialysis (HD) units operate the electronic Kidney Disease Clinical Patient Management System (KDCPMS). KDCMPS is not always used as the primary electronic patient record. At this study setting, KDCPMS information accuracy has not been examined to date. This study aims to identify, characterise and quantify medication discrepancies within KDCPMS records of HD outpatients. Methods Prospective, observational study conducted on the HD unit of Tallaght University Hospital. Medicine reconciliation was conducted to identify KDCPMS discrepancies with medication review to document Drug Related Problems (DRPs). Clinical pharmacists issued recommendations to resolve DRPs. Results All KDCPMS records examined contained intentional and unintentional discrepancies (n=36). Unintentional discrepancies corresponding to 8.8 discrepancies per patient (5.13SD) was observed. One-hundred-and-forty-three DRPs were identified in 34 patients (94.4%). Sixty-five per cent (65%) of pharmacist recommendations were accepted (n=93), 22.4% rejected (n=32), 8.4% (n=12) referred to the renal multidisciplinary team (MDT) and 4.2% not actioned (n=6). Conclusion KDCPMS contains inaccuracies potentially leading to systemic error. Robust clinical governance supported by national policy is required to support KDCPMS as the primary platform for renal patients. Enhanced pharmaceutical care by specialist clinical pharmacists should be supported within national models of care for chronic disease management to improve patient outcomes.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) in Ireland.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the MUC1, UMOD, HNF1B, REN, and SEC61A1 genes. Neither the national or global prevalence of these diseases has been determined. We aimed to establish a database of patients with ADTKD in Ireland and report the clinical and genetic characteristics of these families. Methods: We identified patients via the Irish Kidney Gene Project and referral to the national renal genetics clinic in Beaumont Hospital who met the clinical criteria for ADTKD (chronic kidney disease, bland urinary sediment, and autosomal dominant inheritance). Eligible patients were then invited to undergo genetic testing by a variety of methods including panel-based testing, whole exome sequencing and, in five families who met the criteria for diagnosis of ADTKD but were negative for causal genetic mutations, we analyzed urinary cell smears for the presence of MUC1fs protein. Results: We studied 54 individuals from 16 families. We identified mutations in the MUC1 gene in three families, UMOD in five families, HNF1beta in two families, and the presence of abnormal MUC1 protein in urine smears in three families (one of which was previously known to carry the genetic mutation). We were unable to identify a mutation in 4 families (3 of whom also tested negative for urinary MUC1fs). Conclusions: There are 4443 people with ESRD in Ireland, 24 of whom are members of the cohort described herein. We observe that ADTKD represents at least 0.54% of Irish ESRD patients.

Menopausia y terapia hormonal de la menopausia. Las recomendaciones 2018 de la Unidad de Endocrinología Ginecológica de Clínica Alemana de Santiago -Sociedad Italiana de la Menopausia y la Sociedad Chilena de Endocrinología Ginecológica / Menopause and menopausal hormone therapy. The 2018 recommendations of the Gynecological Endocrinology Unit of Clínica Alemana de Santiago -Italian Society of Menopause and the Chilean Society of Gynecological Endocrinology

ABSTRACT In the last decade, the risk benefits ratio of MHT has been evaluated mainly in terms of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these Recommendations is to provide a simple and updated reference on postmenopausal MHT. The term MHT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential (Seq) when progestogen is added to ERT for 10-14 days a month, or continuous combined (CC) when progestogen is administered continuously every day along with a fixed amount of estrogen. MHT also includes Tibolone and the Tissue Selective Estrogen Complex (TSEC).

Grape pomace in ewes diet: Effects on meat quality and the fatty acid profile of their suckling lambs.

Grape pomace (GP) is an inexpensive natural antioxidant promising as animal feed supplement due to its high content of phenolic compounds. In order to evaluate its effect in lactating ewe rations on meat quality and fat composition of their suckling lambs, 48 Churra ewes were divided into 4 treatments. All animals were fed a ration containing linseed oil (Control) supplemented with Vitamin E or two levels of GP. Lambs were nourished exclusively by suckling until they were slaughtered. Dietary GP did not generate adverse effects on carcasses or lambs meat quality when compared with Control or Vit-E diets. GP improved the water holding capacity of the meat. In addition, lambs meat FA profile was not nutritionally affected with the diets assayed. Hence, the use of GP as a dietary supplement in ewe rations would not have negative effects on meat from suckling lambs.

Home haemodialysis in Ireland.

BACKGROUND: Home haemodialysis (HHD) has the potential to impact positively on patient outcomes and health resource management. There has been rejuvenated international interest in HHD in recent years. AIM: We aimed to review the activity and outcomes of the Irish HHD Programme since inception (2009-16). DESIGN: Retrospective review. METHODS: Patient data were collected using the national electronic Renal Patient database (eMEDRenal version 3.2.1) and individual centre records. All data were recorded in a coded fashion on a Microsoft Excel Spread-sheet and analysed with Stata SE software. RESULTS: One hundred and one patients completed training and commenced HHD; a further fourty-five patients were assessed for HHD suitability but did not ultimately dialyse at home. Twenty patients switched to nocturnal HHD when this resource became available. The switch from conventional in-centre dialysis to HHD led to an increase in the mean weekly hours on haemodialysis (HD) and a reduction in medication burden for the majority of patients. The overall rate of arteriovenous fistula (AVF) as primary vascular access was 62%. Most HHD complications were related to access function or access-related infection. Over the 7-years, 29 HHD patients were transplanted and 9 patients died. No deaths resulted directly from a HHD complication or technical issue. CONCLUSIONS: Patient and technique survival rates compared favourably to published international reports. However, we identified several aspects that require attention. A small number of patients were receiving inadequate dialysis and require targeted education. Ongoing efforts to increase AVF and self-needling rates in HD units must continue. Psychosocial support is critical during the transition between dialysis modalities.

Effect of slaughter age and feeding system on the neutral and polar lipid composition of horse meat.

This study was undertaken to provide a thorough analysis of the neutral lipid (NL) and polar lipid (PL) fractions of horse meat that included the content and distribution of acyl and alkenyl moieties in foals under different rearing conditions. Two groups of crossbred horses were studied; the first group was selected from suckling foals produced under grazing conditions and slaughtered at 4 months of age (n=8), and the second group was selected from concentrate-finished foals and slaughtered at 12 months of age (n=7). There were significant differences related to the age and feeding practices of foals which affected the intramuscular (IM) fat content and the fatty acid (FA) composition of NL and PL fractions. Samples from suckling foals were leaner and provided the highest content of methylation products from the plasmalogenic lipids, and total and n-3 polyunsaturated fatty acid (PUFA). By contrast, the meat from concentrate-finished foals had a higher IM fat level resulting in a greater accumulation of 16:0 and total monounsaturated FAs in the NL fraction, whereas the muscle PL fraction retained a similar FA composition between both groups. Linolenic acid was preferentially deposited in the NL fraction, but linoleic acid and the long-chain n-3 and n-6 PUFAs were incorporated into the PL fraction where they served as cell membrane constituents and in eicosanoid formation.

Agreement between renal prescribing references and determination of prescribing appropriateness in hospitalized patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a risk factor for adverse drug events. The clinical significance of discordance between renal prescribing references is unknown. AIM: We determined the prevalence of potentially inappropriate prescribing (PIP) in CKD, measured agreement between two prescribing references, and assessed potential for harm consequent to PIP. DESIGN: Single-centre observational study. METHODS: A random sample of hospitalized patients with CKD were grouped according to baseline CKD stage (3, 4, or 5). Prescriptions requiring caution in CKD were referenced against the Renal Drug Handbook (RDH) and British National Formulary (BNF) to identify PIP (non-compliance with recommendations). Inter-reference agreement was measured using percentage agreement and Kappa coefficient. Potential for harm consequent to PIP was assessed by physicians and pharmacists using a validated scale. One-year mortality was compared between patients with or without PIP during admission. RESULTS: Among 119 patients (median age 73 years, 50% male), 136 cases of PIP were identified in 78 (65.5%) patients. PIP prevalence, per patient, was 64.7% using the BNF and 28.6% using the RDH (fair agreement, Kappa 0.33, P < 0.001). The majority (63.2%) of PIP cases detected exclusively by the BNF carried minimal or no potential for harm. PIP was not significantly associated with one-year mortality (34.7% vs. 21.1%, P = 0.14). CONCLUSIONS: PIP was common in hospitalized patients with CKD. Substantial discordance between renal prescribing references was apparent. The development of universally-adopted, evidence-based, prescribing guidelines for CKD might optimize medications safety in this vulnerable group.

The Perception of Art among Patients and Staff on a Renal Dialysis Unit.

This study investigated the purpose and effectiveness of giving outpatients an opportunity to engage in art activities while receiving dialysis treatment. A mixed method study was conducted. 21 semi-structured interviews were conducted with outpatients attending the dialysis unit and 13 surveys of clinicians were completed. The principle reasons to partake in the art activity programme included: to pass time, to relieve boredom, to be creative, to try something new, distraction from concerns, to stay positive and to achieve something new. Patients who did not participate in the programme pass their time primarily by watching TV or sleeping. All staff who partook in the survey were satisfied with the programme and wanted it to continue. Our findings indicate that the creative arts programme is viewed positively by staff and patients alike, and might be useful in other hospital departments. Further in depth qualitative research would be useful to interrogate the potential effect of engagement in art on positive mental health and quality of life for patients with chronic conditions.

Effects of grape pomace in growing lamb diets compared with vitamin E and grape seed extract on meat shelf life.

The effect of dietary treatment (CTRL, control; VIT-E, 500 mg kg(-1) vitamin E; GSE, 50 mg grape seed extract kg(-1); GP-5, 5% dried red grape pomace kg(-1)) on shelf life of lamb meat was studied. After slaughter (27 kg LBW), m. longissimus thoracis et lumborum was sliced, packaged under modified atmosphere (80:20%/O2:CO2) and stored in retail conditions for 14 days. At each sampling day (0, 4, 7, 11, 14), microbiological, physico-chemical and sensory characteristics were analysed. Meat from VIT-E presented lower microbial counts than CTRL, GSE and GP-5, without differences between polyphenol treatments (GSE and GP-5) and CTRL. Vitamin E reduced meat discoloration and lipid oxidation (TBARS values) from day 7 with respect to the other treatments. Although not significant, an improvement in TBARS values of about 20% was observed for GSE and GP-5, compared with CTRL, from day 7 of storage. VIT-E dietary treatment was more effective in preventing sensory spoilage than the other treatments.

An Approach to Optimise Therapeutic Vancomycin Dosage in a Haemodialysis Population.

Haemodialysis patients are at risk of gram-positive bacteraemia and commonly require intravenous vancomycin. Intravenously administered vancomycin is primarily excreted by the kidney and exhibits complex pharmacokinetics in haemodialysis patients; achieving therapeutic levels can be challenging. An audit in our unit showed current practises of vancomycin administration resulted in a high proportion of sub-therapeutic levels. A new protocol was developed with fixed weight-based loading and subsequent dosing guided by pre-dialysis levels, target levels were 10-20mg/L. Its effectiveness was prospectively evaluated between 24th September 2012, and 8th February 2013. During this period 25 patients commenced vancomycin, 15 were included. In total, 112 vancomycin levels were taken, 94 (84%) were therapeutic, this was a significant improvement compared to previous practise (odds ratio 5.4, CI 3.1-9.4, p<0.0001). In conclusion, our study shows this protocol can consistently and reliably achieve therapeutic vancomycin levels.

Influence of dietary grape pomace combined with linseed oil on fatty acid profile and milk composition.

Grape pomace is a by-product resulting from the winery industry that is rich in phenolic compounds. It could play a role as an antioxidant and, owing to its high fiber concentration, it would be an alternative ingredient to partially replace forage in the diet of small ruminants. The objective of this study was to evaluate the effect of dietary supplementation of vitamin E or different doses of grape pomace associated with linseed oil on milk fatty acid profile, composition, and yield. Forty-eight Churra ewes were fed with experimental diets consisting of a total mixed ration (TMR) containing 2.7% [on a dry matter (DM) basis] of linseed oil, forage, and concentrate at a 40:60 ratio. Ewes were assigned to 1 of 4 treatments: control (without grape pomace), vitamin E (with 500 mg/kg of TMR of vitamin E), grape pomace-5 (5 g/100 g of TMR of DM of grape pomace), and grape pomace-10 (10 g/100 g of TMR of DM of grape pomace). Experimental diets did not affect DM intake and milk yield and composition. The vitamin E supplementation had only a moderate effect on milk concentration of fatty acids (increase in α-linolenic acid and 16:0 and decrease in cis-9 18:1). Grape pomace supplementation did not affect the percentages of total saturated, monounsaturated, and polyunsaturated fatty acids. Levels of α-linolenic acid reached about 1% of total fatty acids as a consequence of the presence of linseed oil in the diets, were not modified with vitamin E, and remained unaltered in grape pomace-5 and -10 treatments. Linoleic acid was increased by the highest dose of grape pomace, but this ingredient did not modify the cis-9,trans-11 18:2 milk fat content. The concentration of total odd- and branched-chain fatty acids did not diminish in grape pomace-5 and pomace-10 treatments. The presence of grape residue did not modified the trans-11 18:1 and trans-10 18:1 contents, which might indicate that, under the conditions assayed, this winery by-product would not alter the pathways of rumen conversion of dietary unsaturated fatty acids.

An environmental assessment of biodeterioration in document repositories.

Experiments were designed (1) to investigate the bioadhesion, biofilm formation, foxing, and micropitting in documentary collections, (2) to assess the risk of biodeterioration, (3) to investigate the environmental microbial concentration, and (4) to study the influence of environmental factors in biodeterioration of documentary heritage in three archives. The importance of this work in the field of biodeterioration of documentary heritage was verified by bioadhesion and biofilm formation by microorganisms isolated from the collections under study. Bacillus sp. and Scopulariopsis sp. isolated from paper books showed considerable evidence of attacking the paper structure and of pigment production, constituting a hazard to the loss of documentary heritage.

Menopause or climacteric, just a semantic discussion or has it clinical implications?

Climacteric and menopause are two terms that are indistinctly used to name clinical expected events related to the decline in ovarian function. Thus, in the literature and in clinical settings we read and hear 'menopausal symptoms' or 'climacterics symptoms'. Globally, the term menopause is much more frequently used than climacteric but, before we use either one, we should consider that 'menopause' is referring to a specific event, the cessation of menses, and 'climacteric' to gradual changes of ovarian function that start before the menopause and continue thereafter for a while. In the premenopause period, hormonal changes will take place that are associated with symptoms, which deteriorate the quality of life, and with metabolic changes which increase the risk of chronic diseases. Therefore, the word climacteric ('steps' in Greek) seems more adequate to refer to the symptoms and chronic diseases associated with the gradual decrease of ovarian function, and we should leave the term 'menopause' only for naming the event of cessation of menstruation that will happen later as the consequence of the decline in ovarian activity. This differentiation has clinical importance, because it implies that, during the premenopausal period, the impact that the decrease in estrogen has on the health status of women must be assessed and, if it is pertinent, we should indicate lifestyle changes, hormonal therapy, hypolipidemic drugs, etc. It does not seem proper to wait for the cessation of menstrual bleeding before some intervention is started. The decay of women's health starts many years before menopause and prevention of its consequences is a must for us, the clinicians.

A multicenter, randomized controlled trial comparing a single intra-articular injection of Gel-200, a new cross-linked formulation of hyaluronic acid, to phosphate buffered saline for treatment of osteoarthritis of the knee.

OBJECTIVE: To compare the safety and efficacy of a single intra-articular (IA) injection of a new cross-linked hyaluronic acid product, Gel-200, with phosphate buffered saline (PBS, control) in a multi-center randomized controlled trial in patients with symptomatic osteoarthritis (OA) of the knee. DESIGN: Patients were randomized 2:1 to receive a single injection of Gel-200 or PBS, after joint aspiration. The primary measure of effectiveness was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscores by 100-mm Visual Analog Scale (VAS); secondary outcomes included: total WOMAC, physical function, and stiffness subscores; patient and physician global assessments of disease activity, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) strict responders, as well as safety of Gel-200. RESULTS: Of 379 patients randomized, safety was evaluated in 377 and efficacy in 375 (98.9% randomized) in the intent-to-treat population. Effectiveness of Gel-200 by WOMAC pain subscores was statistically significant at week 13 (P=0.037). Mean improvements from baseline in WOMAC pain subscores consistently favored Gel-200 at each visit. Effectiveness of Gel-200 treatment was statistically significant over weeks 3-13 by WOMAC total score, physical function, and physician global evaluations (P<0.05). The number of "strict" OMERACT-OARSI responders was statistically significant from weeks 6 to 13 (P=0.022). Adverse events were not significantly different between treatment groups, including serious adverse events considered related to study treatment. CONCLUSIONS: This trial demonstrated that a single injection of Gel-200 was well tolerated and relieved pain associated with symptomatic OA of the knee over 13 weeks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NTC 00449696.

Effectiveness and Safety of a Multicenter Extension and Retreatment Trial of Gel-200 in Patients with Knee Osteoarthritis.

OBJECTIVE: To assess the continued effectiveness and safety of Gel-200 following observation and open-label retreatment in an extension protocol following a randomized, double-blind, phosphate buffered saline (PBS)-controlled trial (initial treatment trial). DESIGN: Patients who completed initial blinded treatment were allowed to enroll into this extension protocol that permitted retreatment with Gel-200 when eligibility criteria were met. Retreatment was administered with a Gel-200 injection, without knowledge of initial treatment assignment (Gel-200 or PBS). Retreated patients were followed for up to 13 weeks. In the extension phase, durability of response following the first injection was analyzed by time to retreatment eligibility. During separate extension and retreatment phases, responses were assessed by WOMAC pain, stiffness, and physical function subscores, total score, and global assessments of disease activity (patient, physician) as well as safety of Gel-200. RESULTS: In the extension phase, time-to-event analyses through 26 weeks following the initial injection showed statistically significantly longer times to retreatment in patients receiving Gel-200 compared with PBS (P < 0.05). Retreatment with Gel-200, e.g., a second injection, resulted in statistically significant improvements from retreatment baseline in all outcome measures (P < 0.0001). The incidence and type of adverse events after retreatment were comparable to those observed following initial injection of Gel-200 without allergic reactions, including "pseudosepsis" or unanticipated treatment-related serious adverse events. CONCLUSIONS: These data demonstrate that a single injection of Gel-200 resulted in durable effectiveness through 26 weeks and that repeated treatment with Gel-200 relieved symptomatic osteoarthritis with a favorable safety profile.

Visual field defects after selective amygdalohippocampectomy and standard temporal lobectomy.

BACKGROUND: Selective amygdalohippocampectomy (SelAH) is increasingly performed in patients with mesial temporal lobe epilepsy and hippocampal sclerosis. To determine whether visual field defects are less pronounced after SelAH than after standard temporal lobectomy (StTL), we retrospectively analyzed postoperative quantitative visual fields after the 2 procedures. METHODS: Humphrey visual field analysis was obtained postoperatively in 18 patients who had undergone SelAH and in 33 patients who had undergone StTL. The SelAH was performed via a transcortical approach through the middle temporal gyrus and included the amygdala, 3 cm of the hippocampus, and the parahippocampal gyrus. The visual field pattern deviation was used for analysis. We considered a defect clinically significant if there were 3 contiguous coordinates affected at the 5% level or 2 at the 1% level. RESULTS: All but 2 of 18 patients who had undergone SelAH had homonymous superior quadrantic visual field defects contralateral to the side of the surgery. One patient had no defects by our criteria, and one had a mild defect that reached significance only in the ipsilateral eye. The averaged defect affected mostly coordinates close to the vertical meridian with relative sparing of points close to the horizontal meridian. All but 3 of the 33 patients who had undergone StTL had homonymous superior quadrantic visual field defects. One patient had no defects; 2 had defects that reached significance in only one eye. The averaged defect involved all points in the affected quadrant, but was also greater near the vertical meridian. Of 13 tested visual field coordinates, 4 were significantly less affected by SelAH in the ipsilateral eye and 3 in the contralateral eye. The coordinates close to the horizontal meridian were significantly spared by SelAH. CONCLUSIONS: Visual field defects are very common after SelAH but are significantly less pronounced than after StTL. In particular, the visual field close to the horizontal meridian is relatively spared in SelAH.

Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection.

We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng/mL (n = 122, range 2-13.5 ng/mL), Group 2: median 17 ng/mL (n = 123, range 14-20 ng/mL), Group 3: median 24 ng/mL (n = 108, range 20.5-27 ng/mL) and Group 4: median 33.5 ng/mL (n = 116, range 27.5-77.5 ng/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.