Characterization of shrinkage effects in micro-injection moulding (µ-IM)

This thesis characterizes the effects on shrinkage in microinjection moulding. The literature review considers four branches of investigation (material properties, processing parameters, mould design and specimen design). Two research gaps rise from the analysis of the literature review: the absence of a standardized methodology for measuring shrinkage of moulded parts at the micro-scale, and the absence of optimization stage that implements multiple quality criteria. Adequate research routes are set in order to address these gaps. The conventional standard for determining shrinkage at the macro scale is adapted to the micro-scale and this bridges the first gap. The micro-mould replicates the same design of the standard, and a preliminary stage solves some mouldability problems: the implemented mould extended the mouldability range of processing parameters for improving the reliability of results. After the micro-mould validation, the study of shrinkage at the micro-scale considers the influence of five processing parameters: the mould and melt temperature, the holding time and pressure, then the injection pressure. The design of experiment approach identifies the critical parameters that affect moulding, post-moulding and total shrinkage in parallel to and normal to the flow direction within an interval of confidence of 95% for POM and 90% for 316L feedstock. Statistical tools analyse the results, and the trends of critical factors found confirmation in the literature. This methodology at the micro-scale can fill the first gap because it is on purpose designed for the micro-scale. Moreover, the binder of feedstock is a mixture of POM based polymers, and the use of a common platform permits to compare directly the two materials and highlight the influence of powder loading. The optimization stage adopts desirability functions for achieving optimized values that simultaneously fulfil two requests: minimize shrinkage and maximize moulded part mass. The analysis of the literature review shows that few papers adopt multiple quality criteria approach as methodology for optimizing the results, and none consider jointly part mass and shrinkage. The optimized processing parameters allow moulding “optimized specimens”, and results demonstrate that their total shrinkage and part mass achieve the requests. Even if the use of desirability functions produce results thatrepresents a compromise between the requests, the results show that overall shrinkage decreases and part mass increases. This approach demonstrates its reliability and bridges the second gap. The last part of the thesis investigates the 316L feedstock behaviour for filling micro-features parallel to and normal to the flow oriented. The moulded features are investigated for studying the replication quality and the effect of the orientation of channels with dimension close to the feedstock lower mouldability value. These informations are available in the literature only for polymers, and the contribution of this part of thesis is to fill this gap by analysing a feedstock. The statistical approach permits to identify the critical factors that affect the feature replication quality. Optical investigations allow to identify the 316L feedstock lower mouldability value and to observe the influence of the orientation of features with dimensions near the lower limit

Creating movable interfaces by micro-powder injection moulding

This paper presents a novel in situ technique to produce articulated components with high-precision, micro-scale movable interfaces by micro-powder injection moulding (μPIM). The presented process route is based on the use of micro-scale sacrificial layer between the movable subcomponents which is eliminated during the debinding step, creating a dimensionally-controlled, micro-scale mobile interface. The fabrication technique combines the advantages of micro-powder overmoulding, catalytic debinding and sintering. The demonstrated example was a finger bone prosthesis joint consisting of two sub-components with an interface between components of 200 μm in size. The geometries of the sub-components were designed such that they are inseparable throughout the process whilst allowing them to move relative to each other after the debinding stage. The components produced showed the feasibility of the process route to produce readily-assembled meso-, and potentially micro-, scale articulated system

The Holocaust Is a Significant and Independent Risk Factor of Late-Onset Cancers: A Systematic Review of the Literature and Original Data on Jewish Israeli, Jewish Non-Israeli and Non-Jewish Non-Israeli Survivors.

BACKGROUND/AIM: Seventy-six years after Auschwitz Liberation, the Holocaust keeps on persecuting its surviving victims. As witnessed by the psychiatric and medical literature in the last decades, in fact, the Holocaust survivors (HS) appear to suffer from several Shoah-related late-onset diseases impacting their survival, such as internal illnesses and post-traumatic stress disorder (PTSD). Cancer represents a further severe pathology which seems to be connected with the Holocaust experience. Our aim was to review the existing knowledge of Holocaust-related cancer in HS in order to assess its real incidence and clinicoprognostic significance. MATERIALS AND METHODS: We systematically reviewed the literature dealing with Israeli Jewish and non-Jewish non-Israeli HS developing cancer. We also reviewed and analyzed the cancer data of noted Jewish HS not resident or having resided in Israel available as public information. RESULTS: We found 16 and 15 studies on Israeli Jews and non-Jewish non-Israeli survivors, respectively. A statistically significant association between the Holocaust and development of late-onset cancer in HS was seen in most studies with cancer adversely impacting the survival. We also selected 330 noted Jewish non-Israeli HS: genocide-related late-onset cancer resulted to be a significant and independent risk factor of poor prognosis (p<0.0001) imparting shorter survival in affected versus non-cancer subjects (57 versus 64 years, respectively, p=0.0001). CONCLUSION: Although 76 years have passed, our review shows how the Holocaust keeps on burdening its survivors. Moreover, we offered the first analysis of Jewish HS not resident or having resided in Israel in terms of genocide-related late-onset diseases focusing on cancer. Further studies on Jewish non-Israeli HS are needed in order to corroborate our findings on late-onset cancer occurring in this targeted population

Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects

Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43-48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome

Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects

Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43-48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome

Visceral Artery Aneurysms in Liver Transplant Candidates and in Patients after Liver Transplantation

There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of papers on visceral aneurysms in liver transplant patients. The present paper investigates this condition in both groups of patients in a 10-year-retrospective study

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries