The increasing use of Difficult-To-Cut (DTC) alloys for high performance components has recently pushed the implementation of different lubricating/cooling strategies during machining operations in ...order to improve the machinability of these alloys as well as increase the tool life.
Whereas one lubricating/cooling strategy at a time is commonly implemented, the use of two strategies simultaneously, one devoted mainly to lubrication and the other mainly to cooling, hasn't been applied yet to finishing machining operations. To this aim, the objective of the paper is to evaluate the effect of hybrid lubricating/cooling strategies to reduce the tool wear when finishing machining the wrought Ti6Al4V titanium alloy, commonly regarded as a DTC alloy. A commercial Minimum Quantity Lubrication (MQL) system was implemented together with Liquid Nitrogen (LN2) and Carbon Dioxide (CO2) distribution systems designing the position of the nozzles to optimize the lubrication and cooling effects. The tool wear mechanisms were identified and quantified by means of Scanning Electron Microscope (SEM) and optical profiler, respectively. The experimental results showed that the crater wear was predominant when the sole MQL technique was implemented, whereas the use of LN2 and CO2 reduced it, with the most evident advantages highlighted when adopting CO2 that drastically reduced the thermally activated tool wear mechanisms, but still preserving the lubricating effect of the MQL.
It was proved that the adoption of hybrid lubricating/cooling strategies is a viable alternative to the conventional ones, leading to a drastic reduction of the crater wear as well as good surface integrity given an optimized positioning of the lubricant/coolant nozzles.
•We investigated the effect of innovative cooling and lubricating strategies in turning Ti6Al4V.•The low-temperature coolants as LN2 and CO2 reduced the crater wear.•The lubricating strategies mostly affected the surface integrity and flank wear.•The hybrid technologies improved the surface integrity and reduced the tool wear.
Preclinical and some clinical studies suggest a relationship between perturbation in magnesium (Mg2+) homeostasis and pathological anxiety, although the underlying mechanisms remain largely unknown. ...Since there is evidence that Mg2+ modulates the hypothalamic-pituitary adrenal (HPA) axis, we tested whether enhanced anxiety-like behaviour can be reliably elicited by dietary Mg2+ deficiency and whether Mg2+ deficiency is associated with altered HPA axis function. Compared with controls, Mg2+ deficient mice did indeed display enhanced anxiety-related behaviour in a battery of established anxiety tests. The enhanced anxiety-related behaviour of Mg2+ deficient mice was sensitive to chronic desipramine treatment in the hyponeophagia test and to acute diazepam treatment in the open arm exposure test. Mg2+ deficiency caused an increase in the transcription of the corticotropin releasing hormone in the paraventricular hypothalamic nucleus (PVN), and elevated ACTH plasma levels, pointing to an enhanced set-point of the HPA axis. Chronic treatment with desipramine reversed the identified abnormalities of the stress axis. Functional mapping of neuronal activity using c-Fos revealed hyper-excitability in the PVN of anxious Mg2+ deficient mice and its normalisation through diazepam treatment. Overall, the present findings demonstrate the robustness and validity of the Mg2+ deficiency model as a mouse model of enhanced anxiety, showing sensitivity to treatment with anxiolytics and antidepressants. It is further suggested that dysregulations in the HPA axis may contribute to the hyper-emotionality in response to dietary induced hypomagnesaemia.
This article is part of a Special Issue entitled ‘Anxiety and Depression’.
► Robustness and validity of the Mg2+ deficiency model of enhanced anxiety is shown. ► The Mg2+ deficiency model is sensitive to anxiolytic/antidepressant treatments. ► We suggest an inverse relationship between Mg2+ and anxiety. ► An aberrant HPA axis may contribute to the hyper-emotionality of Mg2+ deficiency.
Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of ...five oral hygiene indicators with incident HNCs.
In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption.
Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82, annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer.
Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.
The current paper reports the main results of several studies carried out on Italian workers using the work ability index as a complementary tool for workers' periodical health surveillance. The work ...ability index shows a general decreasing trend over the years, but it changes differently according to working conditions and personal health status. In jobs with higher mental involvement and autonomy, but lower physical constraint, it remains quite constant and high over the years, while it significantly decreases with a steeper trend the higher the physical work load and the lower the job control are. Sex and working hours appear to act concurrently in influencing work ability, particularly in association with more physically demanding jobs. It is therefore necessary to adopt flexible interventions, able to give ageing shift workers a proper support for maintaining a satisfactory work ability, by means of actions addressed both to work organization and psycho-physical conditions.
Abstract Anxiety disorders are the most prevalent central nervous system diseases imposing a high social burden to our society. Emotional processing is particularly controlled by GABA-ergic ...transmission in the amygdala. Using in situ hybridization and immunohistochemistry we now investigated changes in the expression of GABA synthesizing enzymes (GAD65 and GAD67), GABAA (α1–5, β1–3, γ1–2) and GABAB receptor subunits (GBBR1, GBBR2) in amygdaloid nuclei of high anxiety-related behavior (HAB) mice in comparison to mice selected for normal anxiety-related behavior (NAB). Levels of GAD65 and GAD67 mRNAs and protein, as well as those of GABA were increased in the amygdala of HAB mice. Relative to NAB controls, mRNA expression of the GABAA receptor subunits β1, β2 and γ2 was specifically increased in the basolateral amygdala of HAB mice while transcription of α5 and γ1 subunits was reduced in the central and medial amygdala. On the protein level, increases in β2 and γ2 subunit immunoreactivities were evident in the basolateral amygdala of HAB mice. No change in GABAB receptor expression was observed. These findings point towards an imbalanced GABA-ergic neurotransmission in the amygdala of HAB mice. On the other hand, FosB, a marker for neuronal activity, was increased in principal neurons of the basolateral amygdala in HAB mice, reflecting activation of excitatory neurons, possibly as a consequence of reduced GABA-ergic tonic inhibition through α5 and γ1 containing receptors. Ultimately these mechanisms may lead to the compensatory activation of GABA transmission, as indicated by the increased expression of GAD65/67 in HAB mice.
One of the main challenges of the manufacturing industry is to optimise the cutting tool life in order to increase both the process productivity and the product surface quality in machining ...operations. Several innovative strategies were developed and tested as function of both the workpiece material and the peculiar machining operation, being the most interesting in case of difficult-to-cut alloys, the use of low-temperature cutting fluids that would be able to inhibit the thermally activated wear mechanisms responsible of the cutting edge geometrical alterations. In this context, the aim of the paper is to investigate the effect of cryogenic cooling technologies based on the use of liquid nitrogen (LN2) and gaseous nitrogen (N2) cooled at − 100 °C on the tool wear when using uncoated and coated cemented carbide inserts in semi-finishing turning of the Ti6Al4V titanium alloy. Four commercially available insert grades commonly used in machining difficult-to-cut alloys were tested using the cutting parameters recommended by the tool manufacturer. The investigation combined scanning electron microscopy and optical profiler analyses to efficiently define and quantify the main tool wear mechanisms. The study proved that the innovative technology based on cooled N2, regardless of the adopted insert grade, determined the best results in terms of tool life improvement since it simultaneously inhibited the cratering phenomenon onto the tool rake face and produced the lowest flank wear with respect to both the dry cutting, wet strategy, and LN2 cooling cases. It was also proved that the best results were obtained for the uncoated insert when using cooled N2.
Nanomedicine formulations such as biodegradable nanoparticles (nps) and liposomes offer several advantages over traditional routes of administration: due to their small size, nanocarriers are able to ...selectively accumulate inside tumours or inflammatory tissues, resulting in improved drug efficacy and reduced side effects. To further augment targeting ability of nanoparticles towards tumour cells, specific ligands or antibodies that selectively recognise biomarkers over-expressed on cancer cells, can be attached to the surface either by chemical bond or by hydrophilic/hydrophobic interactions. In the present work, Herceptin (HER), a monoclonal antibody (mAb) able to selectively recognise HER-2 over-expressing tumour cells (such as breast and ovarian cancer cells), was absorbed on the surface of nanoparticles through hydrophilic/hydrophobic interactions. Nps were prepared by a modified single emulsion solvent evaporation method with five different polymers: three commercial polyesters (poly(ε-caprolactone) (PCL), poly (d,l-lactide) (PLA) and poly (d,l-lactide-co-.glycolide) (PLGA)) and two novel biodegradable polyesterurethanes (PURs) based on Poly(ε-caprolactone) blocks, synthesised with different chain extenders (1,4-cyclohexane dimethanol (CDM) and N-Boc-serinol). Polyurethanes were introduced as matrix-forming materials for nanoparticles due to their high chemical versatility, which allows tailoring of the materials final properties by properly selecting the reagents. All nps exhibited a small size and negative surface charge, suitable for surface functionalisation with mAb through hydrophilic/hydrophobic interactions. The extent of cellular internalisation was tested on two different cell lines: MCF-7 and SK-BR-3 breast cancer cells showing a normal and a high expression of the HER-2 receptor, respectively. Paclitaxel, a model anti-neoplastic drug, was encapsulated inside all nps, and release profiles and cytotoxicity on SK-BR-3 cells were also assessed. Interestingly, PUR nps were superior to commercial polyester-based nps in terms of higher cellular internalisation and cytotoxic activity on the tested cell lines. Results obtained warrants further investigation on the application of these PUR nps for controlled drug delivery and targeting.
Menkes disease is a rare multisystem X-linked disorder of copper metabolism. Despite an early, severe, and progressive neurologic involvement, our knowledge of brain involvement remains ...unsatisfactory. The first part of this retrospective and review MR imaging study aims to define the frequency rate, timing, imaging features, and evolution of intracranial vascular and white matter changes. According to our analysis, striking but also poorly evolutive vascular abnormalities characterize the very early phases of disease. After the first months, myelination delay becomes evident, often in association with protean focal white matter lesions, some of which reveal an age-specific brain vulnerability. In later phases of the disease, concomitant progressive neurodegeneration might hinder the myelination progression. The currently enriched knowledge of neuroradiologic finding evolution provides valuable clues for early diagnosis, identifies possible MR imaging biomarkers of new treatment efficacy, and improves our comprehension of possible mechanisms of brain injury in Menkes disease.
Emergency or postoperative pain often represents an authentic challenge in patients who were already on opioid treatment for chronic pain. Thus, their management requires not only the physician's ...ability to treat acute pain, but also competence in switching the opioid that lost efficacy. Different aspects should be considered, such as opioids titration, switching, association and equianalgesia. The objective of this paper is to provide a narrative review, which has been elaborated and discussed among clinicians through an iterative process involving development and review of the draft during two web-based meetings and via email. This expert opinion aims to facilitate the correct opioid use through appropriate practices with a focus on pain treatment in emergency and postoperative pain. Equianalgesia tables were reviewed and integrated by clinicians and researchers with expertise in anesthesia, postoperative medicine, intensive care, emergency medicine pharmacology and addiction medicine. Special populations (liver/kidney failure, elder, pediatric, pregnancy/lactation) are discussed in detail along with other critical scenarios, such as: (i) rapid pain worsening in chronic pain (aggravating pain due to disease progression or tolerance development to analgesic therapy); (ii) acute pain on maintenance treatment; and (iii) pain management of complicated patients in emergency care. Extended and updated equianalgesia tables and conversion rates for 17 different opioid formulations (of 9 different molecules) are presented as follows. Opioids remain the class that best suits clinical needs of emergency and post-operative medicine. However, it should be stressed that equianalgesia can be affected by drug-to-drug interactions and pharmacological imprecision, in a complex field where clinical experience may be the main guiding principle.
Background and purpose
Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus‐based ...diagnostic criteria (AE‐DC) allow clinic‐serological subgrouping of AE, with unclear prognostic implications. The impact of AE‐DC on patients’ management was studied, focusing on the subgroup of Ab‐negative‐AE.
Methods
This was a retrospective multicenter study on patients fulfilling AE‐DC. All patients underwent Ab testing with commercial cell‐based assays (CBAs) and, when available, in‐house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab‐positive‐AE N‐methyl‐d‐aspartate‐receptor encephalitis (NMDAR‐E), Ab‐positive limbic encephalitis (LE), definite‐AE or Ab‐negative‐AE (Ab‐negative‐LE, probable‐AE, possible‐AE).
Results
Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab‐negative cases, in‐house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE‐DC, 81 (68.6%) with Ab‐positive‐AE (Ab‐positive‐LE, 40; NMDAR‐E, 32; definite‐AE, nine) and 37 (31.4%) with Ab‐negative‐AE (Ab‐negative‐LE, 17; probable/possible‐AE, 20). Clinical phenotypes were similar in Ab‐positive‐LE versus Ab‐negative‐LE. Twenty‐four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab‐positive or Ab‐negative. Ab‐positive‐AE patients were treated earlier than Ab‐negative‐AE patients (P = 0.045), responded more frequently to treatments (92.3% vs. 65.6%, P < 0.001) and received second‐line therapies more often (33.3% vs. 10.8%, P = 0.01). Delays in first‐line therapy initiation were associated with poor response (P = 0.022; odds ratio 1.02; confidence interval 1.00–1.04).
Conclusions
In‐house diagnostics improved Ab detection allowing better patient management but was available in a patient subgroup only, implying possible Ab‐positive‐AE underestimation. Notwithstanding this limitation, our findings suggest that Ab‐negative‐AE and Ab‐positive‐AE patients share similar oncological profiles, warranting appropriate tumor screening. Ab‐negative‐AE patients risk worse responses due to delayed and less aggressive treatments.
PDF
