Percutaneous tibial nerve stimulation in patients with severe low anterior resection syndrome: randomized clinical trial.

BACKGROUND: Treatment of low anterior resection syndrome (LARS) is challenging. Percutaneous tibial nerve stimulation (PTNS) can improve select bowel disorders. An RCT was conducted to assess the efficacy of PTNS compared with sham stimulation in patients with severe LARS. METHOD: This was a multicentre, double-blind RCT. Patients with major LARS score were allocated to receive PTNS or sham therapy (needle placement simulation without nerve stimulation). The study included 16 sessions of 30 min once a week for 12 consecutive weeks, followed by four additional sessions once a fortnight for the following 4 weeks. The primary endpoint was efficacy of PTNS defined by the LARS score 12 months after treatment. Secondary endpoints included faecal incontinence, quality of life (QoL), and sexual function. RESULTS: Between September 2016 and July 2018, 46 eligible patients were assigned randomly in a 1 : 1 ratio to PTNS or sham therapy. Baseline characteristics were similar. LARS scores were reduced in both groups, but only patients who received PTNS maintained the effect in the long term (mean(s.d.) score 36.4(3.9) at baseline versus 30.7(11.5) at 12 months; P = 0.018; effect size -5.4, 95 per cent c.i. -9.8 to -1.0), with a mean reduction of 15.7 per cent at 12-month follow-up. The faecal incontinence score was improved after 12 months in the PTNS group (mean(s.d.) score 15.4(5.2) at baseline versus 12.5(6.4) at 12 months; P = 0.018). No major changes in QoL and sexual function were observed in either group. There was no therapy-associated morbidity. Three patients discontinued the study, but none owing to study-related issues. CONCLUSION: PTNS has positive effects in some patients with major LARS, especially in those with faecal incontinence. Registration number: NCT02517853 (http://www.clinicaltrials.gov).

High-frequency ultrasound features in a case of gouty panniculitis.

Gouty panniculitis is caused by the deposition of urate crystals in the subcutaneous tissue, accompanied by a lobular panniculitis. It presents as subcutaneous nodules, most commonly located on the lower extremities. Being an unusual clinical presentation of gout, the sonographic findings of gouty panniculitis have been scarcely described in the literature. Our report describes the ultrasound features we found in a case of gouty panniculitis and the usefulness of this technique for diagnosis and monitoring of this disease.

Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin.

BACKGROUND: The different perception and assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) between healthcare providers and patients has not yet been fully addressed, although these two approaches might eventually lead to inconsistent, possibly conflicting interpretation, especially regarding sensory impairment. PATIENTS AND METHODS: A cohort of 281 subjects with stable CIPN was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC v. 2.0) sensory scale, the clinical Total Neuropathy Score (TNSc©), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (mISS) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). RESULTS: Patients' probability estimates showed that the EORTC QLQ-CIPN20 sensory score was overall more highly related to the NCI-CTC sensory score. However, the vibration perception item of the TNSc had a higher probability to be scored 0 for EORTC QLQ-CIPN20 scores lower than 35, as vibration score 2 for EORTC QLQ-CIPN20 scores between 35 and 50 and as grade 3 or 4 for EORTC QLQ-CIPN20 scores higher than 50. The linear models showed a significant trend between each mISS item and increasing EORTC QLQ-CIPN20 sensory scores. CONCLUSION: None of the clinical items had a perfect relationship with patients' perception, and most of the discrepancies stood in the intermediate levels of CIPN severity. Our data indicate that to achieve a comprehensive knowledge of CIPN including a reliable assessment of both the severity and the quality of CIPN-related sensory impairment, clinical and PRO measures should be always combined.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS: After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION: Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

Advanced age and liability to oxaliplatin-induced peripheral neuropathy: post hoc analysis of a prospective study.

BACKGROUND AND PURPOSE: The aim of this post hoc analysis of data extracted from a prospective, multicenter study is to test in a large homogenous population of chemotherapy-naïve patients with colorectal cancer (CRC) treated with oxaliplatin (OXA)-based chemotherapy whether advanced age increases the risk of developing OXA-induced peripheral neuropathy (OXAIPN). METHODS: One-hundred and forty-five patients with CRC, without other significant co-morbidities predisposing to peripheral neuropathy, were divided according to their age into two groups: patients aged between 50 and 68 years (group I, n = 75); and patients aged ≥ 69 years (group II, n = 70). Patients were prospectively monitored at baseline and followed-up during chemotherapy using the motor and neurosensory National Cancer Institute Common Toxicity criteria, the clinical version of the Total Neuropathy Score and neurophysiology. The incidence and severity of both the acute and cumulative OXAIPN was thoroughly determined and then compared between age groups. RESULTS: No statistically significant difference was observed in the incidence of both the acute (n = 64/75 vs. 56/70; P = 0.510) and cumulative OXAIPN (n = 51/75 vs. 49/70; P = 0.858) between age groups. The severity of OXAIPN was also similar between age groups. In line with the clinical data, the neurophysiological results between age groups were also comparable. CONCLUSION: The results of this study indicate that advanced age does not seem to represent a significant risk factor of OXAIPN in patients with CRC without any other significant co-morbidities.

Peripheral neurotoxicity of oxaliplatin in combination with 5-fluorouracil (FOLFOX) or capecitabine (XELOX): a prospective evaluation of 150 colorectal cancer patients.

BACKGROUND: To report our prospective experience on the incidence and pattern of oxaliplatin (OXA)-induced peripheral neuropathy (OXA-IPN) in patients with colorectal cancer (CRC) treated with either FOLFOX-4 or XELoda + OXaliplatin (XELOX). PATIENTS AND METHODS: One hundred and fifty patients scheduled to be treated with either FOLFOX or XELOX for CRC were prospectively monitored at baseline and followed-up during chemotherapy. The incidence and severity of symptoms secondary to OXA-IPN were recorded using three different types of assessment, i.e. the motor and neurosensory National Cancer Institute common toxicity criteria, version 3.0 (NCI-CTCv3), the clinical version of the total neuropathy score (TNSc) and electrophysiological scores. RESULTS: Patients treated with either FOLFOX-4 or XELOX manifested similar incidence rates and severities of acute OXA-IPN. However, FOLFOX-4 was associated with increased incidence of chronic neurotoxicity, compared with XELOX-treated patients (n = 64/77 versus 44/73; P = 0.002), at a very similar OXA median cumulative dose during both regimens. Both the NCI-CTCv3 and TNSc demonstrated that the severity of cumulative OXA-IPN in FOLFOX-4-treated patients is higher than in those treated with XELOX. CONCLUSION: The incidence of acute neurotoxicity during FOLFOX-4 therapy is similar to XELOX. However, it seems that FOLFOX-4 is more neurotoxic than XELOX in terms of cumulative OXA-IPN, despite comparable OXA cumulative dose.

Sick leave request following anti-COVID-19 vaccine administration is low among healthcare workers: results from a retrospective cross-sectional monocentric study.

OBJECTIVE: Anti-COVID-19 vaccines were mainly associated with non-serious adverse events (AEs), whose prevalence was reported to be up to 70% in healthcare workers (HCWs). This may lead to sick leave requests, but this impact has never been quantified. This study aimed to investigate the absence from work among HCWs following anti-COVID-19 vaccination. Its association with age and previous COVID-19 infection was also assessed. PATIENTS AND METHODS: This is a retrospective observational cross-sectional study on administrative data about sick leave requests after anti-COVID-19 vaccination. All the HCWs employed at the Niguarda Hospital (Milan, Italy) who received the vaccine from December 27, 2020 to February 28, 2021 were included. RESULTS: In total, 4,088 HCWs received the first dose of the vaccine and 4,043 completed the vaccination cycle. After the first injection, 1.6% of HCWs requested sick leave, while after the second injection, the number of requests significantly increased (+6.1%, p<0.001). A significant increase in sick leave was detected for those who have had SARS-CoV-2 infection after the first injection (+2.3%, p<0.001). After the second dose, a significant increase in sick leave was observed in the 20-30-year-old group compared to >30 years (+3.6%, p=0.017), if HCWs without a history of SARS-CoV-2 infection were considered. CONCLUSIONS: The requests for sick leave among HCWs following the anti-COVID-19 vaccine were limited and higher after the second injection. This may help the management of the human resources when the large-scale administration of the anti-COVID-19 vaccines will involve other categories of workers.

Meat and fat colour as a tool to trace grass-feeding systems in light lamb production.

Ninety-five lambs were fed as follows: lambs and dams grazing alfalfa (Gr); As Gr but lambs had access to concentrate (Gr+S); ewes grazed and lambs received milk and concentrate until weaning and thereafter concentrate and straw (Rat-Gr); ewes and lambs were stall-fed (Ind). Lambs were slaughtered at 22-24 kg of live-weight and fat and M. rectus abdominis colour measured. Visual appraisal scores of Gr and Ind were significantly different. The absolute value of the integral of the translated spectrum (SUM) was greater in Gr and GR+S. A discriminate analysis was able to discriminate between grass-fed and indoor-fed lambs. A logistic regression including SUM and b(∗) classify correctly 99.1% of carcasses. A equation is proposed to calculate the probability of one carcass to do not belongs to Gr or Gr+S group (PNA): [Formula: see text] .

Near-infrared reflectance spectroscopy for predicting chemical, instrumental and sensory quality of beef.

The aim of this study was to assess near-infrared reflectance (NIR) spectroscopy as a tool for determining sensory and texture characteristics of beef. Chemical, instrumental, texture and sensory characteristics were predicted by near-infrared reflectance spectroscopy carried out on longissimus dorsi muscle samples from 190 young bulls. The use of first derivative gave best predictions together with NIR spectra, except for myoglobin and water holding capacity, which had an R(2) of prediction of 0.91 and 0.82, respectively, using visible and NIR spectra. Tenderness was the best-predicted variable (R(2)=0.98) demonstrating the potential of NIR spectroscopy in the prediction of sensory variables. Chemical composition variables and Warner-Bratzler shear force were predicted with an R(2) of prediction of around 0.7, but protein was not predicted with accuracy.

Binding properties of mono- and dimeric pyridine dicarboxamide ligands to human telomeric higher-order G-quadruplex structures.

Here, we report on the in vitro binding properties of the known pyridine dicarboxamide G-quadruplex ligand 360A and a new dimeric analogue (360A)2A to human telomeric DNA higher-order G-quadruplex (G4) structures. This study points to original binding features never reported for G4 ligands, and reveals a greater efficiency for the dimeric ligand to displace RPA (a ssDNA binding protein involved in telomere replication) from telomeric DNA.

Evaluation of the Profile and Mechanism of Neurotoxicity of Water-Soluble [Cu(P)4]PF6 and [Au(P)4]PF6 (P = thp or PTA) Anticancer Complexes.

[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For these reasons, they have been proposed as a valid alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based compounds were not neurotoxic even at concentrations higher than the IC50 obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 in cancer cell lines. The ability of these compounds to hinder the proteasome machinery in DRG neurons was tested by fluorimetric assay showing that the non-neurotoxic copper-based complexes do not inhibit proteasome activity in DRG primary neuron cultures. On the contrary, the neurotoxic complex [Au(PTA)4]PF6, induced a significant inhibition of proteasome activity even at concentrations lower than the IC50 in cancer cells. The proteasome inhibition induced by [Au(PTA)4]PF6 was associated with a significant increase in α-tubulin polymerization that was not observed following the treatment with copper-based compounds. Uptake experiments performed by atomic absorption spectrometry showed that both copper-based complexes and [Au(PTA)4]PF6 are internalized in neuron cultures. In vitro and in vivo preliminary data confirmed copper-based complexes as the most promising compounds, not only for their anticancer activity but also concerning the peripheral neurotoxicity profile.

Fatty acid composition and sensory traits of beef fed palm oil supplements.

This study measured the effect of replacing dietary fat from an animal source with palm oil supplements on the intramuscular fatty acid profile and sensory quality traits of the meat from young bulls. Thirty-six entire male Friesian calves (mean age=6.8±1.1 months, mean live weight=162.5±28.6kg) were assigned to one of four isoenergetic (1.03 MFU/kg DM) and isoproteinic (15.5% CP) diets, that differed in their fat additives: (D1) lard-tallow mix (control); (D2) hydrogenated palm oil fatty acids (PFA); (D3) calcium salt of partially hydrogenated PFA, and (D4) calcium salt of the fatty acid distillate from palm oil. Bulls (mean live weight=391.3±30.3kg) were slaughtered under commercial conditions and sensory tests were performed to evaluate the effects of the four diets and ageing time (1, 10, and 21d). Only the proportions of C16:0 and C18:0 were significantly affected by the palm oil dietary supplement. Ageing time affected grass odour, tenderness, juiciness, fibrosity, liver flavour, and acid flavour. Nevertheless, palm oil supplements did not negatively alter the organoleptic characteristics of the meat.

Using machine learning procedures to ascertain the influence of beef carcass profiles on carcass conformation scores.

In this study, a total of 163 young-bull carcasses belonging to seven Spanish native beef cattle breeds showing substantial carcass variation were photographed in order to obtain digital assessments of carcass dimensions and profiles. This dataset was then analysed using machine learning (ML) methodologies to ascertain the influence of carcass profiles on the grade obtained using the SEUROP system. To achieve this goal, carcasses were obtained using the same standard feeding regime and classified homogeneous conditions in order to avoid non-linear behaviour in grading performance. Carcass weight affects grading to a large extent and the classification error obtained when this attribute was included in the training sets was consistently lower than when it was not. However, carcass profile information was considered non-relevant by the ML algorithm in earlier stages of the analysis. Furthermore, when carcass weight was taken into account, the ML algorithm used only easy-to-measure attributes to clone the classifiers decisions. Here we confirm the possibility of designing a more objective and easy-to-interpret system to classify the most common types of carcass in the territory of the EU using only a few single attributes that are easily obtained in an industrial environment.

Identifying market segments in beef: Breed, slaughter weight and ageing time implications.

In this paper we propose a method to learn the reasons why groups of consumers prefer some beef products to others. We emphasise the role of groups since, from a practical point of view, they may represent market segments that demand different products. Our method starts representing people's preferences in a metric space; there we are able to define a kernel based similarity function that allows a clustering algorithm to identify significant groups of consumers with homogeneous likes. Finally, in each cluster, we developed, with a support vector machine (SVM), a function that explains the preferences of those consumers grouped in the cluster. The method was applied to a real case of consumers of beef that tasted beef from seven Spanish breeds, slaughtered at two different weights and aged for three different ageing periods. Two different clusters of consumers were identified for acceptability and tenderness, but not for flavour. Those clusters ranked two very different breeds (Asturiana and Retinta) in opposite order. In acceptability, ageing period was appreciated in a different way. However, in tenderness most consumers preferred long ageing periods and heavier to lighter animals.

Effects of whole linseed and rumen-protected conjugated linoleic acid enriched diets on beef quality.

Instrumental assessments and sensory tests were performed to evaluate the effects of diet and postmortem ageing time (1, 7 and 21 days) on beef quality. A total of 48 Friesian calves were randomly allocated to four dietary treatments: control, whole linseed (10% linseed), conjugated linoleic acid (CLA) (2% protected CLA), and whole linseed+CLA (10% linseed and 2% protected CLA). Animals were slaughtered at 458±16.6 kg live weight and 11 months of age. Ageing was more significant than diet on most instrumental parameters. Meat from linseed enriched diets had greater drip loss (P⩽0.001) and intramuscular fat (P⩽0.01) than meat from animals fed CLA. Beef aged for 7 and 21 days had lower cooking losses (P⩽0.01) and shear force (P⩽0.001) than beef aged for 1 day. Lightness was affected only by display time. The addition of CLA in the diet increased hue and yellowness, whereas the inclusion of linseed decreased these values, as well as increased redness. Linseed in the diet decreased fat odour (P⩽0.05), but increased beef (P⩽0.01) and liver (P⩽0.05) flavours. Meat aged for 21 days was significantly more rancid (P⩽0.001), even under vacuum storage. Several organoleptic properties were improved with the inclusion of linseed in the diet, whereas they remained unaffected by the inclusion of CLA.

Carcass characterisation of seven Spanish beef breeds slaughtered at two commercial weights.

A total of 159 bulls representing seven Spanish beef breeds were fed with concentrates, managed in the same conditions and slaughtered at two commercial weights (veal and young-bull). Carcasses were measured and classified in order to characterise the carcass variation in the Spanish beef market and to assess the relationship among carcass measurements and grading. Principal Component Analysis clearly separated commercial types regardless the inclusion of the carcass weight in the input data. Within commercial weights the studied breeds clustered into three groups according to muscular development and carcass classification score: high meat producer breeds (Asturiana de los Valles and Rubia Gallega); medium meat producers (Parda Alpina and Pirenaica); and low meat producers (Avileña, Retinta and Morucha). The perimeter and width of the leg (muscular development) besides the length and width of the carcass basically defined these three carcass types. Conformation was an important trait in explaining variation between breeds because its values were positively correlated with muscular development and carcass compactness.

Picotamide protects mice from death in a pulmonary embolism model by a mechanism independent from thromboxane suppression.

We have previously characterized the new antiplatelet agent picotamide as a dual thromboxane synthase inhibitor/thromboxane A2 receptor antagonist in human platelets. We have now studied the antithrombotic activity of this drug in a simple animal model of lung platelet thromboembolism in the mouse. Picotamide, given i.p. 1 hr before the thrombotic challenge, protected mice from death caused by the i.v. injection of collagen plus epinephrine in a dose-dependent way; the dose reducing mortality by 50% was 277 mg/kg while for aspirin it was 300 mg/kg. Picotamide was also able to reduce the mortality provoked by the i.v. injection of the stable TxA2 mimetic U46619; BM 13.505, a pure TxA2-receptor blocker, was also effective while aspirin was totally inactive. Picotamide, finally, reduced the lethal consequences of the i.v. injection of a 12.5% suspension of hardened rat red blood cells, a model in which platelets are not involved; aspirin was totally ineffective in this model while nicardipine, a calcium channel blocker, was active. Picotamide did not inhibit the formation of TxB2 in serum at any of the doses tested (100 to 750 mg/kg i.p.) while it did enhance significantly PGI2-synthesis from mice aortae and, even more, from mice lungs. The i.v. administration of picotamide (250 mg/kg 2 min before the thrombotic challenge) lead to a strong inhibition of serum TxB2 (-84.6%) and was associated with a higher antithrombotic effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous nitric oxide acts as a natural antithrombotic agent in vivo by inhibiting platelet aggregation in the pulmonary vasculature.

Nitric oxide (NO) is a powerful vasodilator and an inhibitor of platelet aggregation in vitro. While the ability of NO to modulate vascular tone in vivo has been proven, only a few studies have assessed its platelet inhibitory activity in vivo. We have employed two complementary animal models of pulmonary platelet thromboembolism to assess the antithrombotic activity of endogenous NO in vivo. The inhibition of nitric oxide synthase (NOS) by L-NAME significantly potentiated while the administration of the NOS substrate L-arginine significantly reduced the accumulation of 111In-labelled platelets in the pulmonary vasculature of rabbits induced by intravenous collagen plus epinephrine. L-NAME or L-arginine did not, however, modify 111In-labelled erythrocyte distribution in lungs and phenylephrine had no effect on platelet accumulation following collagen + adrenaline, suggesting that the effects of L-NAME were not due to vasoconstriction but rather to a direct modification of platelet function. In mice, L-NAME significantly reduced the dose of collagen + adrenaline required to induce thromboembolic mortality, increased the fall in circulating platelets and increased the % of pulmonary vessels occluded by platelet thrombi. The effects of L-NAME were reversed by L-arginine but not by a dose of nicardipine exerting maximal vasodilatation. Phenylephrine did not potentiate collagen + adrenaline-induced mortality. In the pulmonary vasculature in vivo, endogenous NO inhibits collagen + adrenaline-induced aggregation and enhances platelet disaggregation. This natural modulator function of NO is exerted via a direct effect on platelets and not as a result of haemodynamic changes.

Activation of a ribosomal protein S6 kinase during the 4-dimethylaminoazobenzene-induced rat hepatocarcinogenesis.

During the induction of 4-dimethylaminoazobenzene (DAB) hepatocarcinogenesis there was a progressive increase in the activity of a kinase which specifically phosphorylated S6 ribosomal protein in vitro. Liver tumour tissue (hepatocellular carcinoma and cholangioma) showed maximal activation of this kinase and elevated levels of S6 phosphorylation. Control rats fed with the same diet containing no dye showed a gradual decline of this activity, with low or lacking phosphorylation at the end of the experimental regimen, suggesting close correlation between tumor cell growth and phosphorylation of this ribosomal protein, under these conditions.