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Neuroplasticity in the amygdala and its central nucleus (CeA) is linked to pain modulation and pain behaviors, but cellular mechanisms are not well understood. Here, we addressed the role of small-conductance Ca2+-activated potassium (SK) channels in pain-related amygdala plasticity. The facilitatory effects of the intra-CeA application of an SK channel blocker (apamin) on the pain behaviors of control rats were lost in a neuropathic pain model, whereas an SK channel activator (NS309) inhibited pain behaviors in neuropathic rats but not in sham controls, suggesting the loss of the inhibitory behavioral effects of amygdala SK channels. Brain slice electrophysiology found hyperexcitability of CeA neurons in the neuropathic pain condition due to the loss of SK channel-mediated medium afterhyperpolarization (mAHP), which was accompanied by decreased SK2 channel protein and mRNA expression, consistent with a pretranscriptional mechanisms. The underlying mechanisms involved the epigenetic silencing of the SK2 gene due to the increased DNA methylation of the CpG island of the SK2 promoter region and the change in methylated CpG sites in the CeA in neuropathic pain. This study identified the epigenetic dysregulation of SK channels in the amygdala (CeA) as a novel mechanism of neuropathic pain-related plasticity and behavior that could be targeted to control abnormally enhanced amygdala activity and chronic neuropathic pain.

Background: Fournier’s gangrene (FG) is a fatal condition that often leads to death if not treated properly. To this date, there are no data regarding FG in Indonesia. Objective: This study aims to investigate the characteristics of patients with FG. Methods: A cross-sectional study design was used to evaluate the medical records of patients admitted to Cipto Mangunkusumo Hospital between January 2012 and December 2017. Results: The median age of the subjects were 51 (2-81) years. All of the subjects were male and presented with scrotal pain. The scrotal abscess was found in 38 (88.4%) cases. Type II diabetes was found in 10 (23.3%) subjects. E. coli was the most dominant causative agent in 28 (65.1%) cases. Meropenem was administered in 16 (37.2%) subjects, and 16 (37.2%) subjects had antibiotics administered for ≤7 days. Conclusion: Although the mortality rate has decreased, those with FG tend to have a long hospital stay, which implies a high risk of complications. All males presenting with scrotal pain should be suspected of FG. Further studies on long-term hospitalisation complications in those with FG are required.

Background and Aims: One of the most skilled procedures performed by embryologists is intracytoplasmic sperm injection (ICSI), which takes significant experience to master. Conducting the procedure requires a high level of concentration with training a significant burden on clinical laboratory efficiency. Advancement of a micro 3D printed device to hold oocytes has removed the requirement for a holding pipette, reducing the complexity of the ICSI procedure. This study shows that the microICSIÔ device reduces the technical difficulty of ICSI, improving the speed and precision of the procedure. Method: ICSI was performed conventionally (C-ICSI) and within the microICSIÔ device on abattoir derived porcine denuded oocytes matured in vitro for 39-44 h in NCSU-23 medium containing eCG, hCG, porcine follicular fluid, EGF and insulin. Timing data was captured by video recording for pipette setup and injection time per oocyte for two embryologists and compared between each technique. Oocyte injection time was taken from when a sperm loaded injection pipette was in focus with the oocyte until the injection pipette was removed from the oocyte. Results: Results were compared between C-ICSI and microICSIÔ (Mean ± SD). Pipette setup time was reduced from 278 ± 21 seconds to 109 ± 3 seconds by removing the holding pipette. During the procedure, absence of a holding pipette resulted in embryologists adjusting their hands on average only 3 times during oocyte injection compared to 10 times for C-ICSI when moving between microinjector, pipette and microscope controllers. Oocyte traceability was also improved due to the microICSIÔ device’s numbered array. Embryologist’s injection time was reduced from 42 ± 12 seconds for C-ICSI to 14 ± 5 seconds for microICSIÔ per oocyte. Conclusion: The microICSIÔ device reduces pipette set-up time and the complexity of the ICSI procedure, reducing the time required for oocyte injection by half.

Abstract Calpain 1 and 2 (CPN1/2) are calcium-dependent cysteine proteases that exist in cytosol and mitochondria. Pharmacologic inhibition of CPN1/2 decreases cardiac injury during ischemia (ISC)–reperfusion (REP) by improving mitochondrial function. However, the protein targets of CPN1/2 activation during ISC–REP are unclear. CPN1/2 include a large subunit and a small regulatory subunit 1 (CPNS1). Genetic deletion of CPNS1 eliminates the activities of both CPN1 and CPN2. Conditional cardiomyocyte specific CPNS1 deletion mice were used in the present study to clarify the role of CPN1/2 activation in mitochondrial damage during ISC–REP with an emphasis on identifying the potential protein targets of CPN1/2. Isolated hearts from wild type (WT) or CPNS1 deletion mice underwent 25 min in vitro global ISC and 30 min REP. Deletion of CPNS1 led to decreased cytosolic and mitochondrial calpain 1 activation compared to WT. Cardiac injury was decreased in CPNS1 deletion mice following ISC–REP as shown by the decreased infarct size compared to WT. Compared to WT, mitochondrial function was improved in CPNS1 deletion mice following ischemia–reperfusion as shown by the improved oxidative phosphorylation and decreased susceptibility to mitochondrial permeability transition pore opening. H2O2 generation was also decreased in mitochondria from deletion mice following ISC–REP compared to WT. Deletion of CPNS1 also resulted in less cytochrome c and truncated apoptosis inducing factor (tAIF) release from mitochondria. Proteomic analysis of the isolated mitochondria showed that deletion of CPNS1 increased the content of proteins functioning in regulation of mitochondrial calcium homeostasis (paraplegin and sarcalumenin) and complex III activity. These results suggest that activation of CPN1 increases cardiac injury during ischemia–reperfusion by impairing mitochondrial function and triggering cytochrome c and tAIF release from mitochondria into cytosol.

Post-consumer plasterboard waste sorting is carried out manually by operators, which is time-consuming and costly. In this work, a laboratory-scale hyperspectral imaging (HSI) system was evaluated for automatic refurbishment plasterboard waste sorting. The HSI system was trained to differentiate between plasterboard (gypsum core between two lining papers) and contaminants (e.g., wood, plastics, mortar or ceramics). Segregated plasterboard samples were crushed and sieved to obtain gypsum particles of less than 250 microns, which were characterized through X-ray fluorescence to determine their chemical purity levels. Refurbishment plasterboard waste particles 98 wt%. These findings underpin the potential implementation of an industrial-scale HSI system for plasterboard waste sorting.

Objectives: Because of its multifaceted cardioprotective effects, remote ischemic pre-conditioning (RIPC) was examined as a strategy to attenuate doxorubicin (DOX) cardiotoxicity. Background: The use of DOX is limited by dose-dependent cardiotoxicity and heart failure. Oxidative stress, mitochondrial dysfunction, inflammation, and autophagy modulation have been proposed as mediators of DOX cardiotoxicity. Methods: After baseline echocardiography, adult male CD1 mice were randomized to either sham or RIPC protocol (3 cycles of 5 min femoral artery occlusion followed by 5 min reperfusion) 1 h before receiving DOX (20 mg/kg, intraperitoneal). The mice were observed primarily for survival over 85 days (86 mice). An additional cohort of 50 mice was randomized to either sham or RIPC 1 h before DOX treatment and was followed for 25 days, at which time cardiac fibrosis, apoptosis, and mitochondrial oxidative phosphorylation were assessed, as well as the expression profiles of apoptosis and autophagy markers. Results: Survival was significantly improved in the RIPC cohort compared with the sham cohort (p = 0.007). DOX-induced cardiac fibrosis and apoptosis were significantly attenuated with RIPC compared with sham (p < 0.05 and p < 0.001, respectively). Although no mitochondrial dysfunction was detected at 25 days, there was a significant increase in autophagy markers with DOX that was attenuated with RIPC. Moreover, DOX caused a 49% decline in cardiac BCL2/BAX expression, which was restored with RIPC (p < 0.05 vs. DOX). DOX also resulted in a 17% reduction in left ventricular mass at 25 days, which was prevented with RIPC (p < 0.01), despite the lack of significant changes in left ventricular ejection fraction. Conclusions: Our preclinical results suggested that RIPC before DOX administration might be a promising approach for attenuating DOX cardiotoxicity.

Background: Induction of acute ER (endoplasmic reticulum) stress using thapsigargin contributes to complex I damage in mouse hearts. Thapsigargin impairs complex I by increasing mitochondrial calcium through inhibition of Ca2+-ATPase in the ER. Tunicamycin (TUNI) is used to induce ER stress by inhibiting protein folding. We asked if TUNI-induced ER stress led to complex I damage. Methods: TUNI (0.4 mg/kg) was used to induce ER stress in C57BL/6 mice. Cardiac mitochondria were isolated after 24 or 72 h following TUNI treatment for mitochondrial functional analysis. Results: ER stress was only increased in mice following 72 h of TUNI treatment. TUNI treatment decreased oxidative phosphorylation with complex I substrates compared to vehicle with a decrease in complex I activity. The contents of complex I subunits including NBUPL and NDUFS7 were decreased in TUNI-treated mice. TUNI treatment activated both cytosolic and mitochondrial calpain 1. Our results indicate that TUNI-induced ER stress damages complex I through degradation of its subunits including NDUFS7. Conclusion: Induction of the ER stress using TUNI contributes to complex I damage by activating calpain 1.

Endoplasmic reticulum (ER) stress contributes to cardiovascular disease including heart failure. Interactions between the ER and mitochondria during ER stress can impair the mitochondrial respiratory chain and increase cell injury. p53 is a tumor suppressor protein that regulates apoptosis. p53 contributes to the regulation of mitochondrial and ER interactions, especially during the progression of ER stress. The knockout (KO) of p53 leads to decreased injury in hearts following ischemia-reperfusion. We asked if KO of p53 can protect mitochondria during the induction of ER stress and decrease cell injury. Floxed p53 mice were crossed with mice carrying an α-myosin heavy chain cre to generate cardiac specific p53 KO mice. Thapsigargin (THAP) was used to induce ER stress in wild type (WT) and p53 KO mice. Mice were euthanized after 48 h THAP treatment. Cardiac mitochondria were isolated for functional measurement. TUNEL staining was used to assess myocyte death. In WT mice, THAP treatment decreased the rate of oxidative phosphorylation using pyruvate + malate as complex I substrates compared to vehicle-treated control. Complex I activity was also decreased in the THAP-treated WT mice. The rate of oxidative phosphorylation and complex I activity were not altered in THAP-treated p53 KO mice. The content of pyruvate dehydrogenase (PDH) α1 subunit was decreased in THAP-treated WT mice but not in p53 KO mice. ER stress led to a release of cytochrome c and apoptosis inducing factor from mitochondria into cytosol in WT but not in KO mice. Knockout of p53 also preserved mitochondrial bcl-2 content in THAP-treated mice. In WT mice, THAP treatment markedly increased cell death compared to vehicle treated hearts. In contrast, cell injury was decreased in THAP-treated p53 KO mice compared to corresponding wild type. Thus, KO of p53 decreased cell injury by protecting mitochondria during the ER stress.

In this paper, we present a thought piece examining recent core policing reforms introduced in the Republic of Ireland (ROI), responding to a perceived crisis of legitimacy, for An Garda Síochána (AGS) (translated: ‘The Guardian of the Peace’). Central to this process is the critical reform of the education and training of police and their relationship to the professionalisation and legitimacy of policing. In this paper, we put forward an explorative analysis of the potential link between the professional education of police and their perceived legitimacy. A literature review was carried out on the reform process, including the related elements of police education, training, professionalisation, community policing, police legitimacy, code of ethics (CoE) and police culture. We consider the espoused ambition to professionalise policing via processes including the provision of professional learning in universities and how this might be deemed to contribute (or not) to legitimacy. While no empirical research to date has been carried out on these specific reforms in the ROI, the reform recommendations had several resonances with broader examination of the themes and challenges (in particular police ethics and culture) associated with reform of democratic policing in other jurisdictions, particularly with respect to increasing professional learning and perceived police legitimacy.

The prefrontal cortex (PFC) is a brain region responsible for executive functions including working memory, impulse control and decision making. The loss of these functions may ultimately lead to addiction. Using histological analysis combined with stereological technique, we demonstrated that the PFC is more vulnerable to chronic alcohol-induced oxidative stress and neuronal cell death than the hippocampus. This increased vulnerability is evidenced by elevated oxidative stress-induced DNA damage and enhanced expression of apoptotic markers in PFC neurons. We also found that one-carbon metabolism (OCM) impairment plays a significant role in alcohol toxicity to the PFC seen from the difference in the effects of acute and chronic alcohol exposure on DNA repair and from exaggeration of the damaging effects upon additional OCM impairment in mice deficient in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR). Given that damage to the PFC leads to loss of executive function and addiction, our study may shed light on the mechanism of alcohol addiction.

Purpose: Penile cancer is a rare malignancy, where extranodal extension in inguinal or pelvic lymph nodes is associated with decreased 5-year cancer-survival rate in this study, we try to assess survival and quality of life in a penile cancer patient with bulky lymph node. Methods: We retrospectively reviewed data from penile cancer patients with bulky lymph nodes who underwent treatment between July 2016 and July 2021 at tertiary referral hospital care. The inclusion criteria (age >18 yr, histologically proven penile cancer, and completion of last treatment 6 months prior to this study) yielded a cohort of 20 eligible penile cancer patients with bulky lymph nodes (> 4 cm/bilateral mobile/unilateral fixed). Only patients who had completed therapy at least 6 months prior to the study were included. After obtaining consent, they were asked to complete the EORTC QLQ-C30 questionnaire to evaluate the patient's quality of life. Results: Out of 20 patients, 5 patients underwent direct ILND and 15 patients underwent chemotherapy. Median follow-up after primary diagnosis was 114+32 months in patients with early ILND and 52+11 months in patients who underwent delayed lymph node dissection. Out of 5 patients who underwent early ILND, all of them survived during follow-up, and achieved cancer-free status without residual tumor and with excellent functional outcomes (Karnofsky 90). There was no significant difference in social function (p-value = 0.551), physical function (p-value = 0.272), role function (p-value = 0.546), emotional function (p-value = 0.551), cognitive function (p-value = 0.453), and global health status (p-value = 0.893) between patient which treated with early ILND and Neoadjuvant Chemotherapy. However, patients who underwent early ILND showed a relatively better clinical outcome. Conclusion: Early ILND followed by adjuvant chemotherapy for penile cancer with palpable lymph nodes is more favourable than neoadjuvant TIP chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction Penile cancer is a rare malignancy, where extranodal extension in inguinal or pelvic lymph nodes is associated with decreased 5-year cancer-survival rate in this study, we try to assess survival and quality of life in a penile cancer patient with bulky lymph node. Method We retrospectively reviewed data from penile cancer patients with bulky lymph nodes who underwent treatment between July 2016 and July 2021 at tertiary referral hospital care. The inclusion criteria (age >18 yr, histologically proven penile cancer, and completion of last treatment 6 months prior to this study) yielded a cohort of 20 eligible penile cancer patients with bulky lymph nodes (> 4 cm/bilateral mobile/unilateral fixed). Only patients who had completed therapy at least 6 months prior to the study were included. After obtaining consent, they were asked to complete the EORTC QLQ-C30 questionnaire to evaluate the patient quality of life. Results Out of 20 patients, 5 patients underwent direct ILND and 15 patients underwent chemotherapy. Median follow-up after primary diagnosis was 114+32 months in patient with early ILND and 52+11 months in patients who underwent delayed lymph node dissection. Out of 5 patients underwent early ILND, all of them survived during follow-up, and achieve cancer-free status without residual tumor and with excellent functional outcome (Karnofsky 90). There is no significant difference in social function (p value = 0.551), physical function (p value = 0.272), role function (p value = 0.546), emotional function (p value = 0.551), cognitive function (p value = 0.453), and global health status (p value = 0.893) between patient which treated with early ILND and Neoadjuvant Chemotherapy. However, patient who underwent early ILND showed a relatively better clinical outcome. Early ILND followed by adjuvant chemotherapy for penile cancer with palpable lymph nodes is more favourable than neoadjuvant TIP chemotherapy. [ABSTRACT FROM AUTHOR]