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In Romania, the incidence of malignant melanocytic tumors is continuously increasing. According to the World Health Organization, the incidence of melanocytic and non-melanocytic skin neoplasms has increased considerably and globally, in the last decade. We present the case of a 49-year-old patient who, over the course of 7 years, came in the Plastic Surgery Clinic of the Emergency County Hospital of Craiova for the excision of a number of 25 skin tumor formations, located on the face, cervical region, trunk and upper limbs. Treatment included complete microsurgical excision and supervision. In the end, the patient's treatment compliance decreased significantly. [ABSTRACT FROM AUTHOR]

Melanoma, a deadly form of skin cancer, poses significant challenges to the host immune system, allowing tumor cells to evade immune surveillance and persist. This complex interplay between melanoma and the immune system involves a multitude of mechanisms that impair immune recognition and promote tumor progression. This review summarizes the intricate strategies employed by melanoma cells to evade the immune response, including defective immune recognition, immune checkpoint activation, and the role of regulatory T-cells, myeloidderived suppressor cells, and exosomes in suppressing anti-tumor immunity. Additionally, we discuss potential therapeutic targets aimed at reversing immune evasion in melanoma, highlighting the importance of understanding these mechanisms for developing more effective immunotherapies. Improved insights into the interactions between melanoma and the immune system will aid in the development of novel treatment strategies to enhance anti-tumor immune responses and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Nowadays, a combination of classical subperiosteal implant designs with 3D imaging and printing allows one to reduce treatment time and provides support for fixed prostheses in cases where other techniques do not provide satisfactory results. This study aims to present a digital technique for the manufacturing of custom-made subperiosteal implants and what complications might appear after this type of surgery. Methods: Sixteen patients treated with a custom-made DMLS titanium subperiosteal implant during the period between October 2021 and February 2022 were enrolled in the study. Orthopantomography (OPT) and cone-beam computer tomography (CBCT) were recorded for all patients. The measurements taken into account in this study were the fit and stability of implants, duration of surgery, implant survival, and early and late complications. Results: The fit of the implants was extremely satisfactory, with a mean rating of 4 out of 5. The mean duration of the intervention was 86.18 min. At the end of the study, one implant was lost due to insufficient fit and recurrent, untreatable infections. Eleven implants (69%) were placed on the maxillary and five (31%) implants were placed on the mandible. Conclusions: Taking this into consideration, custom-made DMLS titanium subperiosteal implants could present satisfactory implant survival and low complication rates. [ABSTRACT FROM AUTHOR]

Simple Summary: We have limited information regarding the association and implications of portal venous system (PVS) anomalies in agenesis of ductus venosus (ADV) cases. Few cases of PVS malformations have been reported during fetal life apart from ADV. To the best of our knowledge, this is the first study designed to evaluate the prenatal incidence of ADV and PVS anomalies in the second- and third-trimester anomaly scan experience of a tertiary unit. PVS anomalies were found more frequently than previously reported. We found PVS anomalies in one-third of the ADV cases, while ADV was present in 85.7% of the PVS anomalies. Our data suggest that PVS development is ductus venosus-dependent. PVS anomalies worsened the outcome of ADV cases in our study, and the vast majority of ADV cases that were associated with a normal PVS presented a favorable outcome. The presence of additional fetal anomalies is the best predictor for the outcome of DVA cases. However, an easier evaluation of PVS represents a powerful predictor for ADV cases and addresses the long-term prognosis. To evaluate the prenatal diagnosis of agenesis of ductus venosus (ADV) and portal venous system (PVS) anomalies and describe the outcome of these cases, either isolated or associated. We evaluated the intrahepatic vascular system regarding the presence of normal umbilical drainage and PVS characteristics in the second and third trimester of pregnancy. The associated anomalies and umbilical venous drainage were noted. Follow-up was performed at six months follow-up. Ultrasonography was performed in 3517 cases. A total of 19 cases were prenatally diagnosed: 18 ADV cases, seven abnormal PVS cases, and six associations of the two anomalies. We noted an incidence of 5.1‰ and 1.9‰ for ADV and PVS anomalies, respectively. Out of the 18 ADV cases, 27.7% were isolated. Five cases (26.3%) presented genetic anomalies. PVS anomalies were found in 33.3% of the ADV cases. ADV was present in 85.7% of the PVS anomalies. DV and PVS abnormalities were found with a higher than reported frequency. Normal DV is involved in the normal development of the PVS. Additional fetal anomalies are the best predictor for the outcome of ADV cases. Evaluation of PVS represents a powerful predictor for ADV cases and addresses the long-term prognosis. [ABSTRACT FROM AUTHOR]

The article presents a case study of 7-month-old sexually intact female common marmoset who had a sudden onset of lethargy and inappetence. Topics discussed include the diagnosis of herpes simplex virus (HHV-1) in the marmoset, the necropsy performed on the animal after her death, and the histopathologic examination of the animal. Also mentioned are the clusters of lymphocytes and plasma cells in the cerebrum and cerebellum of the animal.

In this study, we analyze the neuropathological and biochemical alterations involved in the pathogenesis of a neurodegenerative/movement disorder during different developmental stages in juvenile rats with a mutant Myosin5a (Myo5a) . In mutant rats, a spontaneous autosomal recessive mutation characterized by the absence of Myo5a protein expression in the brain is associated with a syndrome of locomotor dysfunction, altered coat color, and neuroendocrine abnormalities. Myo5a encodes a myosin motor protein required for transport and proper distribution of subcellular organelles in somatodendritic processes in neurons. Here we report marked hyperphosphorylation of alpha-synuclein and tau, as well as region-specific buildup of the autotoxic dopamine metabolite, 3,4-dihydroxyphenyl-acetaldehyde (DOPAL), related to decreased aldehyde dehydrogenases activity and neurodegeneration in mutant rats. Alpha-synuclein accumulation in mitochondria of dopaminergic neurons is associated with impaired enzymatic respiratory complex I and IV activity. The behavioral and biochemical lesions progress after 15 days postnatal, and by 30–40 days the animals must be euthanized because of neurological impairment. Based on the obtained results, we propose a pleiotropic pathogenesis that links the Myo5a gene mutation to deficient neuronal development and progressive neurodegeneration. This potential model of a neurodevelopmental disorder with neurodegeneration and motor deficits may provide further insight into molecular motors and their associated proteins responsible for altered neurogenesis and neuronal disease pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin, a phenol in turmeric (Curcuma longa), has been studied for the last decade as a potential anticancer drug. It has been shown to reduce viability of the highly malignant, metastatic rat mammary gland cell line ENU1564 in culture and reduce metastasis of these cells injected into nude mice. The purpose of this study was to identify the mechanisms by which curcumin induces apoptosis in these ENU1564 cells in vitro, and to examine its effects on mitochondrial membrane potential and mitochondrial Ca2+ homeostasis. The results show that curcumin induced apoptosis in ENU1564 cells through the intrinsic pathway of apoptosis, as evident by an increase in mitochondrial Ca2+ accumulation and a decrease in mitochondrial membrane potential. However, treatment of the ENU1564 cells with the mitochondrial uniporter inhibitor RU-360 prior to curcumin treatment partially inhibited the curcumin effects. SKF-96365, a store-operated Ca2+ channel blocker, suppressed the curcumin effect on mitochondrial Ca2+. In addition, curcumin down-regulated the expressions of Bcl-2 and procaspase-3 and increased the production of reactive oxygen species in ENU1564 cells. These data suggest that the mitochondrial Ca2+ is the leading factor by which curcumin induced apoptosis in ENU1564 cells, followed by reactive oxygen species production and inhibition of Bcl-2 oncoprotein. [Copyright &y& Elsevier]

Abstract: Oxidative stress is implicated in various kinds of neurological disorders, including human immunodeficiency virus (HIV) associated dementia (HAD). Our laboratory has been studying the murine retrovirus ts1, a pathogenic mutant of the Moloney murine leukemia virus (MoMuLV), as a model for HAD. Like HIV in humans, ts1 induces oxidative stress and progressive neurodegeneration in mice. We have shown previously that an antioxidant and anti-inflammatory drug GVT or MSL (monosodium luminol) suppresses ts1-induced oxidative stress, attenuates the development of spongiform encephalopathy, and delays hind limb paralysis in infected mice. It is known that upregulation of the nuclear transcription factor NF-E2-related factor 2 (Nrf2) is involved in upregulating cellular antioxidant defenses. Since Nrf2 is associated with elevation of antioxidant defenses in general, and since GVT suppresses ts1-induced neurodegeneration, our aim in this study was to determine whether GVT neuroprotection is linked to Nrf2 upregulation in the brain. We report here that GVT upregulates the levels of Nrf2, both in primary astrocyte cultures and in brainstem of ts1-infected mice. Significant upregulation of Nrf2 expression by GVT occurs in both the cytosolic and nuclear fractions of cultured astrocytes and brainstem cells. Notably, although GVT treatment increases Nrf2 protein levels in cultured astrocytes and brainstem tissues, Nrf2 mRNA levels are not altered. This suggests that the neuroprotective effects of GVT may be mediated by the stabilization of the Nrf2 protein, allowing continuous upregulation of Nrf2 levels in the astrocytes. [Copyright &y& Elsevier]

Abstract: The ts1 mutant of the Moloney murine leukemia virus (MoMuLV) causes neurodegeneration in infected mice that resembles HIV-associated dementia. We have shown previously that ts1 infects glial cells in the brain, but not neurons. The most likely mechanism for ts1-mediated neurodegeneration is loss of glial redox support and glial cell toxicity to neurons. Minocycline has been shown to have neuroprotective effects in various models of neurodegeneration. This study was designed to determine whether and how minocycline prevents paralysis and death in ts1-infected mice. We show here that minocycline delays neurodegeneration in ts1-infected mice, and that it prevents death of cultured astrocytes infected by ts1 through attenuating oxidative stress, inflammation and apoptosis. Although minocycline reduces virus titers in the CNS of infected mice, it does not affect virus titers in infected mice thymi, spleens or infected C1 astrocytes. In addition, minocycline prevents death of primary neurons when they are cocultured with ts1-infected astrocytes, through mechanisms involving both inhibition of oxidative stress and upregulation of the transcription factor NF-E2-related factor 2 (Nrf2), which controls cellular antioxidant defenses. We conclude that minocycline delays retrovirus ts1-induced neurodegeneration involving antioxidant, anti-inflammation and anti-apoptotic mechanisms. [Copyright &y& Elsevier]

Background/Objectives : The present study aims to highlight the possible significant changes due to the COVID-19 pandemic in the resistance of pathogens involved in cases of pediatric infections. Methods : This study included children hospitalized in the Pediatric Intensive Care Unit, Surgery and Pediatrics from a tertiary teaching hospital, during and after the COVID-19 period (2020-2023). Results : The research included 845 samples collected during 2020-2023, from 685 pediatric patients. A total of 937 bacterial isolates were obtained, of which 509 isolates (54.32%) were Gram-negative bacteria. Around 30% of all the pathogens were multidrug-resistant (MDR), with a statistically significant increase post-pandemic, in the case of the MDR Escherichia coli strains ( p < 0.05). A very high percentage of MDR Acinetobacter spp. isolates was found, with an important, but not statistically significant, increase in the post-pandemic period. The highest percentage of the MDR Gram-positive pathogens was registered in the case of S. aureus strains (31.80%). Over 20% of the Coagulase-negative Staphylococci (CoNS) strains isolated between 2020 and 2023 were MDR, with an important increase in the post-COVID-19 period. The proportion of carbapenem-resistant Gram-negative pathogens significantly decreased in the post-COVID-19 period compared with the COVID-19 period ( p < 0.05), especially in the case of the Klebsiella spp. strains. Conclusions : Our findings revealed the increase in the post-COVID-19 period of the prevalence of MDR strains of Acinetobacter spp., CoNS , and Escherichia coli isolated in pediatric patient samples and a significant decline in the trend of the carbapenem-resistant Gram-negative pathogens, which may be due to the testing rate and to the specific pathology of the pediatric patients hospitalized in the two periods.

This article explores the correlation between salivary biomarkers, such as glutathione peroxidase (GPX), total antioxidant capacity (TAC), and superoxide dismutase (SOD), and their association with oral health for children in competitive sports. Saliva has emerged as a valuable resource for evaluating physiological and pathological conditions due to its non-invasive collection method and easy storage. This study examines the potential of GPX, TAC, and SOD as salivary biomarkers for assessing the impact of competitive sports on children's oral health. It discusses the potential implications of increased oxidative stress due to intense physical activity and the role of antioxidant defense mechanisms in maintaining oral health. In total, 173 children aged between 6 and 17 were divided into three groups, 58 hockey players, 55 football players, and 60 in the control group, and examined to assess their oral hygiene and dental and periodontal health. Saliva was collected, centrifuged, and the supernatant was analyzed for the relevant biomarkers. The findings seem to suggest that salivary biomarkers, like GPX, TAC, and SOD, might serve as indicators of the physiological response to competitive sports in children, as well as indicators of oral health, especially dental cavities, and periodontal disease. Statistical analysis showed significant differences between the groups, with better values for athletes, regardless of age, sex, or activity type. Understanding the relationship between salivary biomarkers and competitive sports in children can have significant implications for monitoring and optimizing the health and performance of young athletes. Further research is needed to establish the specific associations between these biomarkers and the effects of several types and intensities of sports activities on oral health in children.

Skin cancer is one of the most common types of cancer, with an increasing worldwide incidence in recent decades. The main risk factor for increasing the skin cancer incidence is ultraviolet (UV) radiation. Of the two major forms of skin cancer (melanomas and non-melanotic cancers), the cutaneous melanoma (CM) is the most aggressive form, causing about 80% of the deaths resulted from this type of tumor. Malignant melanoma develops through malignant transformation of melanocytes in the skin because of prolonged exposure to solar or artificial UV. The malignant transformation of the melanocytes in the skin is accompanied by the presence of a local inflammatory reaction that, in the initial stages of carcinogenesis, would oppose to tumor development. Chronic exposure to UV or other etiopathogenic factors induces chronic inflammation, which, by producing inflammatory molecules (cytokines, chemokines, prostaglandins), constitutes a tumoral microenvironment that favors carcinogenesis, tumor invasion, metastasis, and the presence of neoplastic "mutant cells" that avoid the protective action of the immune system. Using immunohistochemistry techniques, we assessed the intra- and peritumoral inflammatory infiltrate cells in CM. The chronic inflammatory infiltrate presented more intense in the peritumoral stroma compared to the intratumoral one, heterogenous, more intensely composed of lymphocytes, plasma cells, macrophages, and mast cells (MCs), the most numerous cells in the inflammatory infiltrate being T-lymphocytes, plasma cells and macrophages; B-lymphocytes and MCs were in a small number, especially intratumorally. Inflammatory cells had a direct contact with tumor cells, blood vessels, connective matrix, suggesting that the inflammatory microenvironment plays an important role in carcinogenesis, tumor invasion, local angiogenesis, and tumor metastasis.

Hypospadias surgery is a common activity in every department for pediatric surgery, increased incidence of this condition contributing this aspect. For this purpose permanent review of the data of cases is probably necessary, in order to promptly evaluate short and long term results., Material and Methods: The authors are presenting this retrospective clinical and statistical study, enrolling 149 patients, hospitalized and operated in the Department of Pediatric Surgery and Orthopedics, between 2009 and 2018. several parameters were taken into consideration: moment of conception, type of hypospadias, associated malformations, use of meatoplasty, age at meatoplasty, age at urethroplasty, type of urethroplasty, postoperative incidents and complications., Results: Most of the patients included in the study were classified as anterior type of hypospadias, associated malformations were present in 20,13% of the patients, and 80% of the associated malformations belonged to the urogenital system. Over 60% of the cases underwent meatoplasty as a tactical procedure. Mathieu was the most appreciated procedure (74,5%) for urethroplasty and over a half of the patients were operated after the age of 3 years. Early and late postoperative fistula formation was noted in 18,12% of cases., Conclusions: Better parameters to assess the exact type of hypospadias are needed to be introduced. Also, clear protocols for preoperative work-up in detection of other abnormalities, especially genito-urinary. Meatoplasty as a tactical procedure is having unclear influence for urethroplasty. Decreasing the age at urethroplasty should be the next goal. Some surgeons should really get overspecialized for this type of surgery., Competing Interests: None to declare., (Copyright © 2014, Medical University Publishing House Craiova.)

Aim: The authors have proposed to assess peripheral adenopathies in a series of hospitalized children in order to identify and define clinical and morphological profiles of different types of lymph node (LN) diseases., Materials and Methods: The studied group consisted of 58 patients less than 18 years of age. The investigation algorithm included: gender, age, site, involvement, side, extension and histopathological (HP) type of LN lesions. Tissue fragments were processed using classical histological techniques (formalin fixation and paraffin embedment) and stained with Hematoxylin-Eosin (HE). In some cases (tuberculous lesions and lymphomas), special stainings (Ziehl-Neelsen) and immunohistochemistry were used. Stratification scales of cases were defined according to each parameter in order to compare the data. All obtained data were assessed individually, compared to each other and with similar data from the literature with the help of a statistical apparatus [χ² (chi-squared) test and analysis of variance (ANOVA) test] in some cases., Results: The young patients were slightly more frequently boys, of all ages but with a mean age of 10 and half years. The affected LNs belonged most often to neck region, either on the left or on the right side but sometimes bilateral or even on the midline; usually, more than one LN was involved in the area. In most of the cases, the lesions were localized in only one LN area. HP picture was dominated by the inflammatory processes, firstly the nonspecific ones, followed by tuberculosis., Discussions: Our observations fitted, for each parameter, with the wide ranges found in the literature. Comparisons between parameters' variations revealed differences, sometimes significant that we tried to organize in clinical and morphological profiles., Conclusions: The assessment of our data allowed us to define some clinical and morphological profiles of different types of adenopathy that, by improvement on studies including larger series, could be of real use in daily pediatric practice.

Objective: Our objective was to evaluate the accuracy of the prenatal diagnosis and the relation between the type of right aortic arch (RAA) with other intra- or extracardiac (EC) and chromosomal anomalies., Methods: A retrospective, observational study was conducted between 2011-2020 in a Romanian tertiary center. All RAA cases, including double aortic arch (DAA), were extracted from the databases and studied thoroughly., Results: We detected 18 RAA cases: five (27.78%) type I (mirror image, "V" type), 11 (61.12%) type II ("U" type), and two (11.10%) DAA cases. Heart anomalies were associated in 38.89% (overall), 60% (type I), 36.37% (type II), and 0% (DAA) cases. Tetralogy of Fallot represented the most prevalent cardiac malformation (in 22.23% of cases). EC anomalies were present in 44.44% of fetuses (20% of type I, 54.55% of type II, and 50% of DAA cases). Genetic abnormalities were found in 41.17% of pregnancies, with 22q11.2 deletion in 23.53%. 55.55% of the cases had a good neonatal evolution and 44.45% of the pregnancies were terminated. An overall good outcome of pregnancy was noted in 40% of type I RAA, 63.64% of type II RAA, and 50% of DAA cases. All RAA cases examined in the first trimester were correctly diagnosed., Conclusions: RAA can be accurately diagnosed and classified by means of prenatal ultrasound since early pregnancy. A detailed anatomy scan and genetic testing, including 22q11 deletion, should be offered to all pregnancies when RAA is discovered. When isolated, RAA associates a good outcome, indifferently the anatomical type.

Introduction Point of Care Ultrasound (PoCUS) protocols are commonly used to guide resuscitation for patients with undifferentiated hypotension, yet there is a paucity of evidence for any outcome benefit. We undertook an international multicenter randomized controlled trial (RCT) to assess the impact of a PoCUS protocol on key clinical outcomes. Here we report on resuscitation markers.  Methods Adult patients presenting to six emergency departments (ED) in Canada and South Africa with undifferentiated hypotension (systolic blood pressure (SBP) <100mmHg or a Shock Index >1.0) were randomized to receive a PoCUS protocol or standard care (control). Reported physiological markers include shock index (SI), and modified early warning score (MEWS), with biochemical markers including venous bicarbonate and lactate, at baseline and four hours.  Results A total of 273 patients were enrolled, with data collected for 270. Baseline characteristics were similar for each group. Improvements in mean values for each marker during initial treatment were similar between groups: Shock Index; mean reduction in Control 0.39, 95% CI 0.34 to 0.44 vs. PoCUS 0.33, 0.29 to 0.38; MEWS, mean reduction in Control 2.56, 2.22 to 2.89 vs. PoCUS 2.91, 2.49 to 3.32; Bicarbonate, mean reduction in Control 2.71 mmol/L, 2.12 to 3.30 mmol/L vs. PoCUS 2.30 mmol/L, 1.75 to 2.84 mmol/L, and venous lactate, mean reduction in Control 1.39 mmol/L, 0.93 to 1.85 mmol/L vs. PoCUS 1.31 mmol/L, 0.88 to 1.74 mmol/L. Conclusion We found no meaningful difference in physiological and biochemical resuscitation markers with or without the use of a PoCUS protocol in the resuscitation of undifferentiated hypotensive ED patients. We are unable to exclude improvements in individual patients or in specific shock types., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Atkinson et al.)

Objective: There is little consensus on the best way to measure emergency department (ED) crowding. We have previously developed a consensus-based measure, the International Crowding Measure in Emergency Departments. We aimed to externally validate a short form of the International Crowding Measure in Emergency Department (sICMED) against emergency physician's perceptions of crowding and danger., Methods: We performed an observational validation study in seven EDs in five different countries. We recorded sICMED observations and the most senior available emergency physician's perceptions of crowding and danger at the same time. We performed a times series regression model., Results: A total of 397 measurements were analysed. The sICMED showed moderate positive correlations with emergency physician's perceptions of crowding, r = 0.4110, P < 0.05) and safety (r = 0.4566, P < 0.05). There was considerable variation in the performance of the sICMED between different EDs. The sICMED was only slightly better than measuring occupancy or ED boarding time., Conclusion: The sICMED has moderate face validity at predicting clinician's concerns about crowding and safety, but the strength of this validity varies between different EDs and different countries.

Introduction Our previously reported randomized-controlled-trial of point-of-care ultrasound (PoCUS) for patients with undifferentiated hypotension in the emergency department (ED) showed no survival benefit with PoCUS. Here, we examine the data to see if PoCUS led to changes in the care delivered to patients with cardiogenic and non-cardiogenic shock. Methods A post-hoc analysis was completed on a database of 273 hypotensive ED patients randomized to standard care or PoCUS in six centres in Canada and South Africa. Shock categories recorded one hour after the ED presentation were used to define subcategories of shock. We analyzed initial intravenous fluid volumes, as well as rates of inotrope use and procedures. Results  261 patients could be classified as cardiogenic or non-cardiogenic shock types. Although there were expected differences in the mean fluid volume administered between patients with non-cardiogenic and cardiogenic shock (p-value<0.001), there was no difference between the control and PoCUS groups (mean non-cardiogenic control 1881mL (95% CI 1567-2195mL) vs non-cardiogenic PoCUS 1763mL (1525-2001mL); and cardiogenic control 680mL (28.4-1332mL) vs. cardiogenic PoCUS 744mL (370-1117mL; p= 0.67). Likewise, there were no differences in rates of inotrope administration nor procedures for any of the subcategories of shock between the control group and PoCUS group patients. Conclusion Despite differences in care delivered by subcategory of shock, we did not find any difference in key elements of emergency department care delivered between patients receiving PoCUS and those who did not. This may help explain the previously reported lack of outcome differences between groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Atkinson et al.)

Objectives: Point-of-care ultrasound (POCUS) is used increasingly during resuscitation. The aim of this study was to assess whether combining POCUS and electrocardiogram (ECG) rhythm findings better predicts outcomes during cardiopulmonary resuscitation in the emergency department (ED)., Methods: We completed a health records review on ED cardiac arrest patients who underwent POCUS. Primary outcome measurements included return of spontaneous circulation (ROSC), survival to hospital admission, and survival to hospital discharge., Results: POCUS was performed on 180 patients; 45 patients (25.0%; 19.2%-31.8%) demonstrated cardiac activity on initial ECG, and 21 (11.7%; 7.7%-17.2%) had cardiac activity on initial POCUS; 47 patients (26.1%; 20.2%-33.0%) achieved ROSC, 18 (10.0%; 6.3%-15.3%) survived to admission, and 3 (1.7%; 0.3%-5.0%) survived to hospital discharge. As a predictor of failure to achieve ROSC, ECG had a sensitivity of 82.7% (95% CI 75.2%-88.7%) and a specificity of 46.8% (32.1%-61.9%). Overall, POCUS had a higher sensitivity of 96.2% (91.4%-98.8%) but a similar specificity of 34.0% (20.9%-49.3%). In patients with ECG-asystole, POCUS had a sensitivity of 98.18% (93.59%-99.78%) and a specificity of 16.00% (4.54%-36.08%). In patients with pulseless electrical activity, POCUS had a sensitivity of 86.96% (66.41%-97.22%) and a specificity of 54.55% (32.21%-75.61%). Similar patterns were seen for survival to admission and discharge. Only 0.8% (0.0-4.7%) of patients with ECG-asystole and standstill on POCUS survived to hospital discharge., Conclusion: The absence of cardiac activity on POCUS, or on both ECG and POCUS together, better predicts negative outcomes in cardiac arrest than ECG alone. No test reliably predicted survival.

Borrelia burgdorferi is a tick-borne bacterium responsible for approximately 300,000 annual cases of Lyme disease (LD) in the United States, with increasing incidences in other parts of the world. The debilitating nature of LD is mainly attributed to the ability of B. burgdorferi to persist in patients for many years despite strong anti- Borrelia antibody responses. Antimicrobial treatment of persistent infection is challenging. Similar to infection of humans, B. burgdorferi establishes long-term infection in various experimental animal models except for New Zealand White (NZW) rabbits, which clear the spirochete within 4 to 12 weeks. LD spirochetes have a highly evolved antigenic variation vls system, on the lp28-1 plasmid, where gene conversion results in surface expression of the antigenically variable VlsE protein. VlsE is required for B. burgdorferi to establish persistent infection by continually evading otherwise potent antibodies. Since the clearance of B. burgdorferi is mediated by humoral immunity in NZW rabbits, the previously reported results that LD spirochetes lose lp28-1 during rabbit infection could potentially explain the failure of B. burgdorferi to persist. However, the present study unequivocally disproves that previous finding by demonstrating that LD spirochetes retain the vls system. However, despite the vls system being fully functional, the spirochete fails to evade anti- Borrelia antibodies of NZW rabbits. In addition to being protective against homologous and heterologous challenges, the rabbit antibodies significantly ameliorate LD-induced arthritis in persistently infected mice. Overall, the current data indicate that NZW rabbits develop a protective antibody repertoire, whose specificities, once defined, will identify potential candidates for a much-anticipated LD vaccine., (Copyright © 2019 American Society for Microbiology.)

Study Objective: Point-of-care ultrasonography protocols are commonly used in the initial management of patients with undifferentiated hypotension in the emergency department (ED). There is little published evidence for any mortality benefit. We compare the effect of a point-of-care ultrasonography protocol versus standard care without point-of-care ultrasonography for survival and clinical outcomes., Methods: This international, multicenter, randomized controlled trial recruited from 6 centers in North America and South Africa and included selected hypotensive patients (systolic blood pressure <100 mm Hg or shock index >1) randomized to early point-of-care ultrasonography plus standard care versus standard care without point-of-care ultrasonography. Diagnoses were recorded at 0 and 60 minutes. The primary outcome measure was survival to 30 days or hospital discharge. Secondary outcome measures included initial treatment and investigations, admissions, and length of stay., Results: Follow-up was completed for 270 of 273 patients. The most common diagnosis in more than half the patients was occult sepsis. We found no important differences between groups for the primary outcome of survival (point-of-care ultrasonography group 104 of 136 patients versus standard care 102 of 134 patients; difference 0.35%; 95% binomial confidence interval [CI] -10.2% to 11.0%), survival in North America (point-of-care ultrasonography group 76 of 89 patients versus standard care 72 of 88 patients; difference 3.6%; CI -8.1% to 15.3%), and survival in South Africa (point-of-care ultrasonography group 28 of 47 patients versus standard care 30 of 46 patients; difference 5.6%; CI -15.2% to 26.0%). There were no important differences in rates of computed tomography (CT) scanning, inotrope or intravenous fluid use, and ICU or total length of stay., Conclusion: To our knowledge, this is the first randomized controlled trial to compare point-of-care ultrasonography to standard care without point-of-care ultrasonography in undifferentiated hypotensive ED patients. We did not find any benefits for survival, length of stay, rates of CT scanning, inotrope use, or fluid administration. The addition of a point-of-care ultrasonography protocol to standard care may not translate into a survival benefit in this group., (Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Medication reconciliation at transitions of care increases patient safety. Collection of an accurate best possible medication history (BPMH) on admission is a key step. National quality indicators are used as surrogate markers for BPMH quality, but no literature on their accuracy exists. Obtaining a high-quality BPMH is often labour- and resource-intensive. Pharmacy students are now being assigned to obtain BPMHs, as a cost-effective means to increase BPMH completion, despite limited information to support the quality of BPMHs obtained by students relative to other health care professionals., Objectives: To determine whether the national quality indicator of using more than one source to complete a BPMH is a true marker of quality and to assess whether BPMHs obtained by pharmacy students were of quality equal to those obtained by nurses., Methods: This prospective trial compared BPMHs for the same group of patients collected by nurses and by trained pharmacy students in the emergency departments of 2 sites within a large health network over a 2-month period (July and August 2016). Discrepancies between the 2 versions were identified by a pharmacist, who determined which party (nurse, pharmacy student, or both) had made an error. A panel of experts reviewed the errors and ranked their severity., Results: BPMHs were prepared for a total of 40 patients. Those prepared by nurses were more likely to contain an error than those prepared by pharmacy students (171 versus 43 errors, p = 0.006). There was a nonsignificant trend toward less severe errors in BPMHs completed by pharmacy students. There was no significant difference in the mean number of errors in relation to the specified quality indicator (mean of 2.7 errors for BPMHs prepared from 1 source versus 4.8 errors for BPMHs prepared from ≥ 2 sources, p = 0.08)., Conclusions: The surrogate marker (number of BPMH sources) may not reflect BPMH quality. However, it appears that BPMHs prepared by pharmacy students had fewer errors and were of similar quality (in terms of clinically significant errors) relative to those prepared by nurses., Competing Interests: Competing interests: Ashley Sproul has received grants from the Dalhousie Endowment Fund and the Medbuy Red Fund for work outside this submission. Carole Goodine has received a summer student grant from Sanofi Aventis, also for work outside this submission. No other competing interests were declared.

Background: Two distinct Emergency Medical Services (EMS) systems exist in Atlantic Canada. Nova Scotia operates an Advanced Emergency Medical System (AEMS) and New Brunswick operates a Basic Emergency Medical System (BEMS). We sought to determine if survival rates differed between the two systems., Methods: This study examined patients with trauma who were transported directly to a level 1 trauma centre in New Brunswick or Nova Scotia between 1 April 2011 and 31 March 2013. Data were extracted from the respective provincial trauma registries; the lowest common Injury Severity Score (ISS) collected by both registries was ISS≥13. Survival to hospital and survival to discharge or 30 days were the primary endpoints. A separate analysis was performed on severely injured patients. Hypothesis testing was conducted using Fisher's exact test and the Student's t-test., Results: 101 cases met inclusion criteria in New Brunswick and were compared with 251 cases in Nova Scotia. Overall mortality was low with 93% of patients surviving to hospital and 80% of patients surviving to discharge or 30 days. There was no difference in survival to hospital between the AEMS (232/251, 92%) and BEMS (97/101, 96%; OR 1.98, 95% CI 0.66 to 5.99; p=0.34) groups. Furthermore, when comparing patients with more severe injuries (ISS>24) there was no significant difference in survival (71/80, 89% vs 31/33, 94%; OR 1.96, 95% CI 0.40 to 9.63; p=0.50)., Conclusion: Overall survival to hospital was the same between advanced and basic Canadian EMS systems. As numbers included are low, individual case benefit cannot be excluded., Competing Interests: Competing interests: IW reports a potential competing interest from the NB Trauma Program. During the conduct of the study he had a salaried position with the New Brunswick Trauma Program. SB reports a potential competing interest from the NB Trauma Program. During the conduct of the study she had a salaried position with the New Brunswick Trauma Program., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction Patients with low-acuity (Canadian Triage and Acuity Scale level IV and V) complaints use the emergency department (ED) to access care. This has often been attributed to lack of a primary care provider. However, simply being registered with a primary care provider may not prevent low acuity ED presentation. There is some evidence that a lack of timely access to primary care may contribute to low acuity ED presentations. The Wait Time Alliance, a group of Canadian physicians and their respective professional associations, has recently set a benchmark of same day access to family doctors. It is unclear if this benchmark has been achieved in all jurisdictions.  Methods We performed linked cross sectional surveys to quantify the number of people presenting to the ED for nonurgent problems who felt unable to access primary care. Primary care practices were also surveyed to assess access using the metric of time to third next available appointment.  Results In the patient survey, 381 of 580 patients consented to participate. Of the 89 patients who met eligibility criteria, 100% completed the survey. 32 (35.9%) reported that the wait to see their primary care provider was "too long". 45 (50.5%) patients did not contact their primary care provider's office prior to ED presentation. 45 of 72 physician surveys were returned; a response rate of 62.5%. Most (77%) physicians estimated their wait time for a standard appointment to be greater than 48 hours. The mean calculated time to third next available appointment in the region was 6.6 (95% CI 4.6-8.7) days. Conclusions Approximately half of low acuity patients do not attempt to access their primary care provider prior to ED presentation. The benchmark of same day access to primary care has not been achieved in many practices in our region. Further education regarding primary care access would likely be beneficial to both patients and providers., Competing Interests: The authors have declared that no competing interests exist.

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies.

Gastrointestinal stromal tumors could rise in different areas of the digestive tract, at any age, but very rarely in neonates. We present the case of a 5-day-old male, with intestinal stenosis and atresia (type II) operated for peritonitis. On the resected specimen, the histopathological examination revealed a small gastrointestinal tumor of 8 mm. The immunohistochemical analysis indicated a low malignant potential. He is currently at two years of oncologic follow-up with no evidence of disease.

Background: Curcumin is one of the most studied natural compounds which has been used as a feed additive for centuries. Curcumin exhibits low oral bioavailability in rodents and human. Curcumin formulated with phosphatidylcholine (Meriva) increases curcumin bioavailability five-fold compared to original curcumin. The aim of this study was to evaluate the efficacy of curcumin conjugated with phosphatidylcholine as an anticancer agent., Materials and Methods: In this xenograft study, mammary gland tumor cell line (ENU1564) was inoculated into the mammary fat pad of athymic nude mice. The mice were treated orally with either curcumin or Meriva. The tumor and its lung metastasis were evaluated grossly, microscopically, and immunohistochemically., Results: Meriva significantly reduced the expression of MMP-9 and lung metastasis of our cell line used in this experimental model., Conclusion: Curcumin conjugated with phosphatidylcholine increased the efficacy of curcumin as an anticancer agent.

Matrix metalloproteinase-9 (MMP-9) plays a critical role in tumor invasion and metastasis. Here, we investigate the effect of fibroblast growth factor-1 (FGF-1) on the expression of MMP-9 in ENU1564, an ethyl-N-nitrosourea-induced rat mammary adenocarcinoma cell line. We observed that FGF-1 induces a dose-dependent increase in MMP-9 mRNA, protein, and activity in ENU1564 cells. To gain insight into the molecular mechanism of MMP-9 regulation by FGF-1, we investigated the role of components of PI3K-Akt and MEK1/2-ERK signaling pathways in our system since NF-kappaB and AP-1 transcription factor binding sites have been characterized in the upstream region of the MMP-9 gene. We demonstrated that FGF-1 increases Akt phosphorylation, triggers nuclear translocation of NF-kappaBp65, and enhances degradation of cytoplasmic IkappaBalpha. Pretreatment of cells with LY294002, a PI3K inhibitor, significantly inhibited MMP-9 protein expression in FGF-1-treated cells. Conversely, our data show that FGF-1 increases ERK phosphorylation in ENU1564 cells, increases c-jun and c-fos mRNA expression in a time-dependent manner, and triggers nuclear translocation of c-jun. Pretreatment of cells with PD98059, a MEK1/2 inhibitor significantly inhibited MMP-9 protein expression in FGF-1 treated cells. Finally, we observed increased DNA binding of NF-kappaB and AP-1 in FGF-1-treated cells and that mutation of either NF-kappaB or AP-1 response elements prevented MMP-9 promoter activation by FGF-1. Taken together, these results demonstrated that FGF-1-induced MMP-9 expression in ENU1564 cells is associated with increasing DNA binding activities of NF-kappaB and AP-1 and involve activation of a dual signaling pathway, PI3K-Akt and MEK1/2-ERK., ((c) 2007 Wiley-Liss, Inc.)

Because of the overwhelming scattering of light in biological tissues, the spatial resolution and imaging depth of conventional fluorescent imaging is unsatisfactory. Therefore, we present a dual modality imaging technique by combining fluorescence imaging with high-resolution noninvasive photoacoustic tomography (PAT) for the study of an animal tumor model. PAT provides high-resolution structural images of tumor angiogenesis, and fluorescence imaging offers high sensitivity to molecular probes for tumor detection. Coregistration of the PAT and fluorescence images was performed on nude mice with M21 human melanoma cell lines with ..v..3 integrin expression. An integrin ..v..3-targeted peptide-ICG conjugated NIR fluorescent contrast agent was used as the molecular probe for tumor detection. PAT was employed to noninvasively image the brain structure and the angiogenesis associated with tumors in mice. The coregistration between the PAT and fluorescence images was used to visualize tumor location, angiogenesis, and brain structure simultaneously.

Optical contrast is sensitive to functional parameters, including the oxygen saturation and total concentration of hemoglobin, in biological tissues. However, due to the overwhelming scattering encountered by light in tissues, traditional optical modalities cannot provide satisfactory spatial resolution beyond the ballistic (a few hundred microns) and quasiballistic (1-2 mm) regimes. Photoacoustic tomography is based on the high optical contrast yet utilizing the high ultrasonic resolution. Our work in this emerging area of research will be summarized in this invited talk. In this technology, a diffraction-based inverse-source problem is solved in the image reconstruction, for which we developed the rigorous reconstruction theory. We implemented a prototype and accomplished noninvasive transdermal and transcranial functional imaging of small-animal brains in vivo. Change in the cerebral blood oxygenation of a rat, as a result of the alternation from hyperoxia to hypoxia, was imaged successfully.

An experimental colony of Berlin Druckrey IV (BD IV) rats with inherited, congenital, gradually progressive incoordination and rear limb ataxia was evaluated for clinical signs, gross and microscopic nervous system lesions, and mode of inheritance of the gene defect. Clinical evaluation suggested a lesion in the midbrain or brainstem, with resulting lower motor neuron functional impairment. Gross alterations in affected rats were atrophy of thigh musculature by six months of age and thoracic kyphoscoliosis. Histological evaluation of the nervous system revealed central chromatolysis of neurons within the red nuclei in 20 out of 24 affected rats. Additionally, in six out of 24 affected rats chromatolytic neural cell bodies of this nucleus contained brightly eosinophilic, coarsely granular, cytoplasmic deposits. Special stains (osmium tetroxide, Kinyoun's acid-fast and periodic acid-Schiff) indicated these deposits consisted of lipopolysaccharide. Additional lesions in ataxic rats included qualitative reduction in neuronal cell bodies of the inferior olivary nucleus (10 out of 26 rats) and cerebellar Purkinje cells (5 out of 27 rats). No reduction in the number of spinal cord lower motor neurons was detected. Analysis of intercross pedigrees that were established between ataxic BD IV females and either normal Long Evans or Fisher males indicated a likely autosomal recessive mode of inheritance. The authors propose that this disease accompanying a new variant of the BD IV rat (to be designated "shaker" rat) provides a new and unique research model for ataxia with features in common with some human hereditary ataxias.