higher early postoperative mortality in surgically treated IE patients after dedicated adjustment for confounding. In this perspective, any effort to improve preoperative microbiological diagnosis, thus allowing targeted therapeutic initiatives, might lead to overall better postoperative outcomes in surgically treated IE.

In our cohort, CNIE was associated with a higher early postoperative mortality in surgically treated IE patients after dedicated adjustment for confounding. In this perspective, any effort to improve preoperative microbiological diagnosis, thus allowing targeted therapeutic initiatives, might lead to overall better postoperative outcomes in surgically treated IE.Our commentary is focused on three studies that used microRNA overexpression methods for directed differentiation of stem cells into insulin-producing cells. Islet transplantation is the only cell-based therapy used to treat type 1 diabetes mellitus. However, due to the scarcity of cadaveric donors and limited availability of good quality and quantity of islets for transplant, alternate sources of insulin-producing cells are being studied and used by researchers. This commentary provides an overview of distinct studies focused on manipulating microRNA expression to optimize differentiation of embryonic stem cells or induced pluripotent stem cells into insulin-producing cells. These studies have used different approaches to overexpress microRNAs that are highly abundant in human islets (such as miR-375 and miR-7) in their differentiation protocol to achieve better differentiation into functional islet beta (β)-cells.2019 novel coronavirus disease (COVID-19, previously known as novel coronavirus pneumonia) was first discovered in December 2019 and spread widely in China and all over the world in 2020. The initial symptoms of most patients include fever, cough, and fatigue. Dyspnea may occur with the progress of the disease, and acute respiratory distress syndrome may occur in severe cases. The CT manifestations of this disease are mainly ground-glass opacity (GGO) in the lung, which may be accompanied by patchy consolidation, and fibrous changes may appear in the lung at the later stage of the disease. Combined with typical clinical and imaging findings and positive nucleic acid test results, the disease can be diagnosed. We report the first case of novel coronavirus disease (COVID-19) in Heilongjiang Province, China. The patient was seriously ill, who felt that he suffered from fever, fatigue, cough, and expectoration and sought medical treatment, with a history of contact with Wuhan. The leukocyte count was normal, and the lymphocyte count was decreased. CT imaging showed large GGO and partial patchy consolidation in both lungs. The patient recovered and was discharged after 26 days of treatment. This study is helpful for early diagnosis and timely clinical management by mastering the typical imaging of novel coronavirus disease (COVID-19).

Many factors contribute to successful nerve reconstruction. The correct technique of anastomosis is one of the key elements that determine the final result of a surgery. The aim of this study is to examine how useful an electromyography (EMG) can be as an objective intraoperative anastomosis assessment method.

The study material included 12 rats. Before the surgery, the function of the sciatic nerve was tested using hind paw prints. Then, both nerves were cut. The left nerve was sutured side-to-side, and the right nerve was sutured end-to-end. Intraoperative electromyography was performed. After 4 weeks, the rats were reassessed using the hind paw print analysis and electromyography.

An analysis of left and right hind paw prints did not reveal any significant differences between the length of the steps, the spread of the digits in the paws, or the deviation of a paw. The width of the steps also did not change.Electromyography revealed that immediately after a nerve anastomosis (as well as 4 weeks after or example, in limb replantation.When assessing a nerve during a procedure, EMG should be first performed distally to the anastomosis (the part of the nerve leading to muscle fibers) and then proximally to the anastomosis (the proximal part of the nerve). Similar EMG results can be interpreted as a correct nerve anastomosis.The function of the distal part of the nerve and the muscle remains intact if the neuromuscular transmission is sustained.Primary secondary tumor increased recently with the use of immunomodulatory drugs in patients with multiple myeloma (MM). However, MM with prior diagnosis of primary secondary tumor is relatively rare. In this study, we reported an MM patient with prior diagnosis of rectal cancer. In brief, an 85-year-old man was first diagnosed with rectal cancer. Given the age, heart failure and small-cell hypochromic anemia (hemoglobin level 54 g/L), rectal cancer resection was not advised and symptomatic treatments were performed (including sufficient iron supplementation). Eight months later, the patient was diagnosed with MM due to worsening anemia. Anemia and heart failure were corrected after three cycles of treatment with thalidomide, dexamethasone and capecitabine. Radical resection of rectal carcinoma (Hartmann) was finally performed due to acute abdominal distension. Meanwhile, RR interval prolongation (longest interval >5.0 s) and atrial fibrillation occurred in the fifth cycle treatment. One month after discontinuation of thalidomide, RR interval returned to normal range, while atrial fibrillation developed into persistent atrial fibrillation.

Cutaneous melanoma is an aggressive cancer with increasing incidence and mortality rates worldwide. Metastasis is one of the primary elements that influence the prognosis of patients with cutaneous melanoma. This study aims to clarify the potential mechanism underlying the low survival rate of metastatic melanoma and to search for novel target genes to improve the survival rate of patients with metastatic tumors.

Gene expression dataset and clinical data were downloaded from The Cancer Genome Atlas portal. Differentially expressed genes (DEGs) were identified, and their functions were studied through gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Survival and multivariate Cox regression analyses were used to screen out candidate genes that could affect the prognosis of patients with metastatic melanoma.

After a series of comprehensive statistical analysis, 464 DEGs were identified between primary tumor tissues and metastatic tissues. Survival and multivariate Cox regression analyses revealed four vital genes, namely,

,

,

, and

, that affect the prognosis of patients with metastatic melanoma.

This study provides a new direction for studying the pathogenesis of metastatic melanoma. The genes related to cutaneous metastatic melanoma that affect the overall survival time of patients were identified.

This study provides a new direction for studying the pathogenesis of metastatic melanoma. The genes related to cutaneous metastatic melanoma that affect the overall survival time of patients were identified.This study aims to examine a time-extended dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) protocol and report a comparative study with three different pharmacokinetic (PK) models, for accurate determination of subtle blood-brain barrier (BBB) disruption in patients with multiple sclerosis (MS). This time-extended DCE-MRI perfusion protocol, called Snaps, was applied on 24 active demyelinating lesions of 12 MS patients. Statistical analysis was performed for both protocols through three different PK models. The Snaps protocol achieved triple the window time of perfusion observation by extending the magnetic resonance acquisition time by less than 2 min on average for all patients. In addition, the statistical analysis in terms of adj-R2 goodness of fit demonstrated that the Snaps protocol outperformed the conventional DCE-MRI protocol by detecting 49% more pixels on average. The exclusive pixels identified from the Snaps protocol lie in the low ktrans range, potentially reflecting areas with subtle BBB disruption. Finally, the extended Tofts model was found to have the highest fitting accuracy for both analyzed protocols. The previously proposed time-extended DCE protocol, called Snaps, provides additional temporal perfusion information at the expense of a minimal extension of the conventional DCE acquisition time.

In Italy, both parents have parental responsibility, so they have the power to give or withhold consent to medical procedures on their children.

The present work reports the case of a 5-year-old boy diagnosed with neuroblastoma in the right adrenal loggia, who underwent several chemotherapy treatments that prolonged his life until the age of 10. Informed consent for treatments was requested exclusively of the parents, without taking into consideration the minor’s will, not even when he asked for increased pain relief medication instead of other palliative treatments.

The authors thought it interesting to examine the case in the light of new Italian legislation on informed consent and to verify whether it promotes greater participation of minors in healthcare choices, given that the issue of acquisition of informed consent is becoming increasingly broad and complex.

The case examined here indicates that current Italian legislation, even including the modifications introduced, does not allow for concrete and active participation of minors, especially those under the age of 12, in the discussion of choices about their health, not even in choices regarding the end of life, and not even when the minor manifests a mature capacity for discernment.

The case examined here indicates that current Italian legislation, even including the modifications introduced, does not allow for concrete and active participation of minors, especially those under the age of 12, in the discussion of choices about their health, not even in choices regarding the end of life, and not even when the minor manifests a mature capacity for discernment.

The incidence of laryngeal tuberculosis has increased gradually in recent years. Laryngeal tuberculosis has strong infectivity and atypical clinical manifestations. Hence, establishing the early diagnosis of laryngeal tuberculosis is considered difficult, resulting in the high rate of misdiagnosis of laryngeal tuberculosis and increased rates of tuberculosis infection.

This study aimed to describe a case of laryngeal tuberculosis detected using the mycobacteria gene chips technology, facilitating the early diagnosis and the treatment of laryngeal tuberculosis.

A 27-year-old woman presented with a 7-day history of hoarseness, with a normal routine blood chemistry test and chest computed tomography results. Histological analysis of the vocal cord biopsy showed granulomatous inflammation and the negative acid-fast stain test. The mycobacteria gene chips method was used to directly examine the vocal cord tissue treated with homogenate, and the

was successfully identified. Thus, the early diagnosis of laryngeal tuberculosis and the drug sensitivity of rifampin and isoniazid were confirmed. The patient recovered after undergoing a 1-year standard anti-tuberculosis therapy.

Mycobacterial identification on homogenised biopsy using the mycobacteria gene chips method significantly facilitates the early diagnosis and the treatment of tuberculosis.

Mycobacterial identification on homogenised biopsy using the mycobacteria gene chips method significantly facilitates the early diagnosis and the treatment of tuberculosis.The present study aimed to analyze the data of embedded intrauterine device (IUD) in the bladder wall with the additional presence of calculus. This case series study included 11 female patients with partially or completely embedded IUD in the bladder wall. Their median age was 34 (range, 32-39) years. The median duration of IUD placement was 36 (range, 24-60) months. The median duration of symptoms was 9 (range, 3-12) months. Six patients underwent laparoscopy the operation duration was 129 (range, 114-162) min, blood loss was 15 (range, 10-25) mL, the hospital stay was 4 (range, 4-4.5) days, the visual analog scale (VAS) for pain at 6 h after surgery was 3 (range, 2-6), and the time to removal of the urethral catheter was 7 (range, 7-8) days. Five patients underwent open surgery the operation duration was 126 (range, 96-192) min, blood loss was 30 (range, 20-50) mL, the hospital stay was 7 (range, 7-15) days, the VAS was 6 (range, 4-9) at 6 h after surgery, and the time to removal of the urethral catheter was 9 (range, 8-17) days. The IUD and bladder stones were successfully removed in all 11 (100%) patients.Osteoprotegerin (OPG) appears to be a very promising marker both in the diagnosis of abdominal aortic aneurysms (AAAs) and as a potential target in its treatment. This article presents an overview of the current literature that discusses the role of OPG in the pathogenesis of atherosclerosis and its potential value as a prognostic factor in AAA. Pharmacological modulation of OPG expression has been considered. In conclusion, it seems that further research designed to assess the relationship between OPG and AAA is needed as this may contribute to improved AAA monitoring and more effective treatment of patients with AAA.Post-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy. We studied 35 patients with cardiac death and suspected cardiomyopathy based on autopsy or clinical data. After targeted sequencing, we identified 15 causal variants in 15 patients (yield 43%) in sarcomeric (n = 8), desmosomal (n = 3), lamin A/C (n = 3) and transthyretin (n = 1) genes. The results had various impacts on families, i.e. allowed predictive genetic testing in relatives (15 families), planned early therapeutics based on the specific underlying gene (5 families), rectified the suspected cardiomyopathy subtype (2 families), assessed the genetic origin of cardiomyopathy that usually has an acquired cause (1 family), assessed the diagnosis in a patient with uncertain borderline cardiomyopathy (1 family), reassured the siblings because of a de novo mutation (2 families) and allowed prenatal testing (1 family). Our findings suggest that post-mortem molecular testing should be included in the strategy of family care after cardiac death and suspected cardiomyopathy, since genetic findings provide additional information useful for relatives, which are beyond conventional autopsy.Retinoic acid receptor-related orphan receptors (RORs) are frequently abnormally expressed in several human malignancies, including gastric cancer (GC). RORs are involved in the development and progression of GC through Wnt signaling pathway receptors and other common receptors. However, the prognostic roles of individual RORs in patients with GC remain elusive. We accessed the prognostic roles of three RORs (RORα, RORβ, and RORγ) through „The Kaplan-Meier plotter” (KM plotter) database in patients with GC. For all patients with GC who were followed for 20 years, the low mRNA expression of all three RORs showed a significant correlation with better outcomes. We further accessed the prognostic value of individual RORs in different clinical pathological features including Lauren classification, clinical stages, pathological grades, HER2 status, and different treatments methods. The RORs demonstrated critical prognostic roles in GC. Expressions of RORs were higher in GC tissues when compared with normal gastric tissues. Moreover, knockdown of RORs significantly inhibited cell proliferation and migration, suggesting an oncogenic role of RORs in human GC. These findings suggest potential roles of RORs as biomarkers for GC prognosis and as oncogenes in GC.Recent studies have revealed that microRNAs regulate radiosensitivity of non-small cell lung cancer (NSCLC). The aim of this study was to investigate whether miR-101-3p is correlated with radiosensitivity of NSCLC. According to our results, miR-101-3p was downregulated in NSCLC tissues and cell lines. Moreover, miR-101-3p was decreased in A549 cells’ response to irradiation in a dose-dependent manner. Upregulation of miR-101-3p decreased survival fraction and colony formation rate and increased irradiation-induced apoptosis in irradiation-resistant cells, while miR-101-3p depletion had the opposite effects in irradiation-sensitive cells. Furthermore, mechanistic target of rapamycin (mTOR) is a target gene of miR-101-3p. The expressions of mTOR, p-mTOR, and p-S6 were curbed by overexpression of miR-101-3p in A549R cells, which was enhanced by repression of miR-101-3p in A549 cells. Intriguingly, elevation in mTOR abated miR-101-3p upregulation-induced increase in irradiation sensitivity in irradiation-resistant cell line. In contrast, rapamycin undermined miR-101-3p inhibitor-mediated reduction of irradiation sensitivity in irradiation-sensitive cell line. Besides, miR-101-3p overexpression enhanced the efficacy of radiation in an NSCLC xenograft mouse model. In conclusion, miR-101-3p sensitized A549 cells to irradiation via inhibition of mTOR-signaling pathway.

The aim of this study was to investigate the effects of rehabilitation training on Notch1 and synaptophysin (SYN) levels in brain tissues of rats with chronic cerebral ischemia.

Eighty-one male Sprague-Dawley rats were divided into nine groups three Sham groups, three Model groups, and three training groups. There were nine rats in each group. At different time points, the apoptosis cell rate was analyzed by the TUNEL assay, and the expression levels of Notch1 and SYN in brain tissues were analyzed by immunohistochemical staining and RT-qPCR assay.

The apoptosis cell rate of training groups was significantly higher on day 28 (

< 0.05). The protein and mRNA levels of both Noth1 and SYN in training groups were significantly higher on day 28 (

< 0.05).

Rehabilitation training could improve nerve cell apoptosis by increasing the expression of both Notch1 and SYN.

Rehabilitation training could improve nerve cell apoptosis by increasing the expression of both Notch1 and SYN.

The association between

(

) gene -572 G^C polymorphism and myocardial infarction (MI) risk has not been established. We adopted this meta-analysis for further insight into the case-control studies.

To investigate the genetic association, we searched multiple databases, including Web of Science, EMbase, CBM disc, PubMed and CNKI. Also, we manually identified the searched references. All the statistical analyses were conducted using Stata 11.0.

A total of five studies were identified, involving 2,526 MI cases and 3,027 controls. The results revealed a significant association between

gene -572 G^C polymorphism and MI, implying that the

gene -572 C allele may be a protective factor for MI (for C allele vs K allele OR = 0.85, 95% CI = 0.73-0.99,

= 0.041; for C/C vs G/G OR = 0.55, 95% CI = 0.31-0.98,

= 0.044; for C/C vs G/C + G/G OR = 0.60, 95% CI = 0.41-0.89,

= 0.011). However, in the subgroup analysis with regard to ethnicity, no significant correlation was identified between

gene -572 G^C polymorphism and MI among Europeans.

The

gene -572 C allele may be a protective factor for MI. Future studies involving larger sample bases are still recommended.

The IL-6 gene -572 C allele may be a protective factor for MI. Future studies involving larger sample bases are still recommended.Osteoarthritis (OA) is a common medical problem leading to chronic pain and physical disability among the world’s population. Analyzing the molecular background of the degenerative arthritis creates the potential for developing novel targeted methods of treatment. Fifty samples of meniscus, anterior cruciate ligaments (ACLs) and articular surfaces were collected from patients who underwent total knee arthroplasty in 2016. Enzyme-linked immunosorbent assay was used to assess the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF), transforming growth factor-β1 and LUMINEX for MMP-1, MMP-2, MMP-3, MMP-9 and MMP-13. The collected data were correlated with the severity of radiological OA, demographic data and clinical scales. Strong positive correlations in the concentration of metalloproteinases and proinflammatory cytokines, TNF-α (MMP-2 and MMP-13) and IL-6 (MMP-13), were identified. MMP-13 had a positive correlation with the concentration of MMP-1, MMP-2 and MMP-9. Negative correlation coefficient exists between clinical conditions measured with the Western Ontario and McMaster Universities Osteoarthritis Index scale and the level of TNF-α and MMP-1. The TNF-α concentration was lower in the cartilage of the articular surface among patients who took non-steroidal anti-inflammatory drugs periodically. The decrease in MMP-2 in the cartilage of the articular surface corresponded with the severity of radiological OA on the Kellgren-Lawrence scale. Current treatment methods for OA do not stop disease progression. Identifying signaling pathways and molecular particles engaged in OA and their correlations with the patient’s clinical condition brings new therapeutic possibilities.Sirtuin 6 (SIRT6) plays a critical role in the progression and development of gastrointestinal cancers. However, the association between SIRT6 expression and clinicopathological parameters and prognosis in gastrointestinal cancer patients remains inconclusive. Consequently, we conducted this meta-analysis to evaluate the importance of SIRT6 expression in various types of gastrointestinal cancers. PubMed, EMBASE, and Web of Science databases were systematically searched to screen the relevant literature. The reported or estimated hazard ratio (HR) and odds ratio (OR) and their corresponding 95% confidence interval (CI) were pooled to assess the strength of the association. Nine studies involving 867 patients were included in the meta-analysis. Overall analysis showed that high SIRT6 expression was related to better overall survival in gastrointestinal cancers (HR = 0.62, 95% CI = 0.47-0.82). High SIRT6 expression was also related to a favorable tumor node metastasis (TNM) stage (OR = 0.44, 95% CI = 0.28-0.70) among gastrointestinal cancer patients. Our meta-analysis revealed that high SIRT6 expression might be a potential biomarker predicting better prognosis in gastrointestinal cancers, which may offer options for gastrointestinal cancer treatment.Pericentric inversion in chromosome 1 was thought to cause male infertility through spermatogenic impairment, regardless of the breakpoint position. However, carriers of pericentric inversion in chromosome 1 have been reported with normal fertility and familial transmission. Here, we report two cases of pericentric inversion in chromosome 1. One case was detected in utero via amniocentesis, and the other case was detected after the wife of the carrier experienced two spontaneous abortions within 5 years of marriage. Here, the effect of the breakpoint position of the inversion in chromosome 1 on male infertility is examined and compared with the published cases. The association between the breakpoint of pericentric inversion in chromosome 1 and spermatogenesis is also discussed. Overall, the results suggest that the breakpoint position deserves attention from physicians in genetic counseling as inversion carriers can produce offspring.

Acute kidney injury (AKI) is a common complication of sepsis. Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays a vital role in various diseases, including AKI. This study aimed to investigate the function and mechanism of NEAT1 in sepsis-induced AKI.

A septic AKI model was established by treating HK-2 cells with lipopolysaccharide (LPS). The levels of NEAT1 and miR-22-3p were measured by quantitative real-time PCR. Cell apoptosis was assessed by flow cytometry. The levels of apoptosis-related protein and autophagy-related factors were examined by the western blot assay. An enzyme-linked immunosorbent assay was used to calculate the contents of inflammatory factors. The interaction between NEAT1 and miR-22-3p was validated by dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay. The levels of nuclear factor (NF)-κB pathway-related proteins were evaluated by the western blot assay.

NEAT1 was upregulated, while miR-22-3p was downregulated in patients with sepsis and in LPS-stimulated HK-2 cells. LPS treatment triggered cell apoptosis, autophagy, and inflammatory response in HK-2 cells. NEAT1 knockdown attenuated LPS-induced cell injury. NEAT1 modulated LPS-triggered cell injury by targeting miR-22-3p. Furthermore, NEAT1 regulated the NF-κB pathway by modulating miR-22-3p.

Depletion of NEAT1 alleviated sepsis-induced AKI via regulating the miR-22-3p/NF-κB pathway.

Depletion of NEAT1 alleviated sepsis-induced AKI via regulating the miR-22-3p/NF-κB pathway.Amyloidosis is a group of idiopathic clinical syndromes caused by the deposition of insoluble fibrillar proteins (amyloid) in the extracellular matrix of organs and tissues. These deposits disrupt the function of the target organ. Amyloidosis can manifest as a systemic disease or a single-organ involvement (local form). Its etiology still remains unclear. Deposits of amyloid in the larynx are rare, accounting for between 0.2 and 1.2% of benign tumors of the larynx. In this retrospective study, we report the clinical aspects, diagnosis, treatment and follow-up of five female patients with localized laryngeal amyloidosis without systemic involvement. The patients were all treated successfully using microlaryngoscopy with CO2 laser or cold instruments. Prognosis is excellent; however, appropriate follow-up is an important part of the long-term management of this disease in order to prevent and control the possibility of local recurrence.

S100A6 protein (calcyclin), a small calcium-binding protein of the S100 family, is often upregulated in various types of cancers, including hepatocellular carcinoma (HCC). The aim of this study was to illustrate the molecular mechanism of S100A6 in regulating the proliferation and migration of HCC cells.

The expressions of S100A6 in human HCC and adjacent non-tumor liver specimens were detected using immunoblotting and quantitative PCR (qPCR). The recombinant glutathione S-transferase (GST)-tagged human S100A6 protein was purified and identified. After treatment with S100A6, the proliferation of HepG2 cells was detected by the MTT and colony formation assay, and the migration of HepG2 cells was investigated by the transwell migration assay; the protein levels of cyclin D1 (CCND1), E-cadherin, and vimentin were also tested by immunoblotting. The effect of S100A6 on p21 and nuclear factor-κB pathway was verified by performing the dual luciferase assay. Then, the expression of p21 and its transcription activator, p53, was examined using immunoblotting and qPCR, the ubiquitination of which was investigated through co-immunoprecipitation.

It was found that the level of S100A6 was higher in the HCC tissues than in the adjacent non-tumor liver specimens. Exogenous overexpression of S100A6 promoted the proliferation and migration of HepG2 cells. S100A6 was observed to regulate p21 mRNA and protein expression levels and decrease p53 protein expression level, not mRNA level, by promoting the ubiquitination of p53 via the proteasome-dependent degradation pathway.

Our study indicated that S100A6 overexpression could promote the proliferation and migration of HCC cells by enhancing p53 ubiquitin-dependent proteasome degradation, ultimately regulating the p21 expression level.

Our study indicated that S100A6 overexpression could promote the proliferation and migration of HCC cells by enhancing p53 ubiquitin-dependent proteasome degradation, ultimately regulating the p21 expression level.

Individuals with prenatal alcohol exposure (PAE) often present with a myriad of other prenatal (e.g. exposure to tobacco and other illicit drugs, poor prenatal care) and postnatal risk factors (e.g. multiple home placements, physical/sexual abuse, low socio-economic status)-all of which are likely contributing to their adverse outcomes.

A comprehensive neuropsychological battery, coupled with magnetic resonance imaging, was administered to children with fetal alcohol spectrum disorders (FASD) in 2009. Study participants diagnosed with FASD by the University of Washington using the FASD 4-Digit Code were compared to typically-developing peers with no PAE. Data from this MRI study were used to explore the proportion of variance in brain structural and functional abnormalities explained by PAE and 14 other prenatal and postnatal risk factors.

PAE was the dominant risk factor explaining the largest proportion of variance in regional brain size (total brain, frontal lobe, caudate, hippocampus and corpus callosum) and brain function (intellect, achievement, memory, language, executive-function, motor, adaptation, behavior-attention and mental health symptoms). Other prenatal and postnatal risk factors were 3 to 7-fold more prevalent than in the general population. Individually, each risk factor explained a statistically significant, but smaller proportion of variance in brain outcome compared to PAE. In combination, the proportion of variance explained by the presence of multiple prenatal and postnatal risks rivaled that of PAE.

A better understanding of the impact other prenatal and postnatal risk factors have on the neurodevelopmental outcomes of individuals with FASD can inform more effective prevention and intervention strategies.

A better understanding of the impact other prenatal and postnatal risk factors have on the neurodevelopmental outcomes of individuals with FASD can inform more effective prevention and intervention strategies.Burnout has become an increasingly recognized problem in higher medical education and is particularly prevalent within the field of Neurology and its training programs. Many previously reported wellness initiatives in other residencies focused mainly on community/team building. We developed a comprehensive Wellness Curriculum (WC) and established a new role of Resident Wellness Liaison in order to facilitate wellness across the department and training program. Here we present a 6-step outline of our WC which can easily be adapted to the needs of other programs. The steps include creating a Wellness Committee with a Resident Wellness Liaison, identification and optimization of institutional resources, identifying and troubleshooting barriers to wellness, providing education and reflection on wellness, showing appreciation to each other, and assessing the impact of the implemented strategies. In order to measure the impact of our WC and to perform a needs assessment for future directions, we posed questions-grounded in the theory of drivers of burnout and engagement-to our residents (N = 24) at a noon conference in the summer of 2020. Interventions implemented at our institution have been very well received by residents, as evidenced by their comments and feedback. Themes that were highlighted by residents include enjoying flexibility, having a welcoming social support system at work, and being able to find meaning in the day-to-day work. The creation of a comprehensive WC is a feasible and meaningful intervention for addressing resident wellness in a Neurology training program and could be adapted to other programs.Postoperative complications after total thyroidectomy with extensive neck dissection in thyroid malignancies are well documented in the current literature. However, sinus bradycardia as a postthyroidectomy complication is a rare phenomenon and, to the best of our knowledge, few studies have identified it as a perioperative condition. In our study, we report a case of 9-year-old boy with papillary thyroid carcinoma, who underwent total thyroidectomy and bilateral neck dissection. Postoperatively, the surgery was complicated by initial vocal cord paresis and chyle leak. The patient also suffered from asymptomatic sinus bradycardia which self-resolved. Although causative factors cannot be determined by a single case, hypothyroidism, carotid sinus hypersensitivity, and bilateral damage to the middle cervical sympathetic ganglion could play a significant role in this uncommon pathophysiological condition.Introduction  Pediatric circumcision is a commonly performed operation, yet outcomes related to procedures performed for medical indications remain underreported. Aim  The aim of this study was to report outcomes of therapeutic circumcision from our center. Methods  Prospective registry of elective circumcisions was maintained and analyzed at a single institution in the United Kingdom. Data collected included information on complications (early and late), emergency presentations, and referrals back from primary care services. Results  Between August 2015 and June 2019, 300 patients (mean age 9 years; range 3-16 years) underwent therapeutic circumcision. The average length of follow-up data available was 2.1 years (range 6 months to 4 years). The overall complication rate was 4.7% ( n  = 16). There were no unplanned admissions and no cases returned to the operating room as emergency. Only 1% ( n  = 3) of patients presented with an early complication (minor bleeding, pain, urinary retention), and 3.7% ( n  = 11) suffered a late complication (meatal stenosis [2.7%]). All cases of meatal stenosis had lichen sclerosus confirmed on histology. Cosmetic satisfaction was 99%. Conclusion  Therapeutic circumcision is an effective procedure in the pediatric population, which carries a low risk of early and late complications. Our study found that meatal stenosis only occurred in those patients with confirmed lichen sclerosus histology.Raoultella planticola , a gram-negative bacterium, first emerged in late 1900s as Klebsiella planticola . It was later classified as Raoultella genus in 2001. This nonmotile rod is usually found in soil and aquatic environment. There are two known species of Raoultella R. planticola and R. ornithinolytica . They are responsible for numerous yet rare infections including cystitis, pneumonia, and bacteremia. To date, only one case of joint or bone infection due to R. planticola has been reported. The infection is eradicated after arthroscopic lavage and antibiotic therapy with fluoroquinolones. We present the first case of septic arthritis due to R. planticola involving a native knee joint following synovectomy during arthroscopy.Pyrexia of unknown origin (PUO) has been a diagnostic challenge for decades. Hepatic hemangioma (HH) is not a common differential diagnosis of PUO. It is the most common benign hepatic tumor, commonly asymptomatic and incidentally detected, or can present with vague abdominal pain. PUO is a rare presenting feature. We describe a case of 38-year-old lady presenting with PUO. With no other identifiable source of fever despite exhaustive investigations, a giant hemangioma in right lobe of liver detected on abdominal ultrasonography was deemed to be the cause of PUO. The patient had sudden decrease in hemoglobin while undergoing workup, which on imaging showed a bleeding hemangioma and right hepatectomy was performed. Patient had an uneventful recovery and her PUO also resolved after surgery. HH should be considered a rare diagnosis of exclusion for PUO after a standard algorithmic approach does not reveal any other cause.Background  Central pancreatectomy (CP), a partial resection of the pancreas, is indicated for the excision of neuroendocrine tumors (NETs) of the pancreas, when located at the neck or the proximal body. Specifically, CP is preferable in functional NET and in nonfunctional sized 1 to 2 cm or/with proliferation marker Ki67  less then  20% (Grade I/II). Postoperative leakage from the remaining pancreas constitutes the most frequent complication of CP (up to 63%). The aim of our study was to share the experience of our center in CP for NET, with pancreaticojejunal anastomosis. Methods  In 1 year, we performed CP in two patients, following the aforementioned criteria. They presented with tumor of the body of the pancreas, which was found in random check with computed tomography, with negative hormonal blood tests and they underwent magnetic resonance imaging and endoscopic ultrasound/fine-needle biopsy/pathological examination. Results  The patients underwent CP with Roux-en-Y pancreaticojejunal anastomosis of the distal pancreatic stump and jejunal patch of the proximal pancreatic stump. Histological exam revealed NET sized 2.8 cm and 1.45 cm, Grade I and II, respectively. Postoperatively both patients developed small pancreatic leakage, which did not affect their physical condition and stopped after 20 and 30 days. No one needed pancreatic enzymes supplements or developed new-onset diabetes mellitus. Conclusion  CP provided adequate, functional remaining pancreatic tissue in both patients. Small leakages were treated conservatively and retreated without septic complications. As a result, CP might be considered as safe and effective technique for pancreatic neck/proximal body NET.

The risk of infection associated with specific treatments of chronic active antibody-mediated rejection (cAMR) after kidney transplantation remains unknown.

This was a single-center study of kidney transplant recipients treated with pulse steroids, intravenous immunoglobulin (IVIG) ± rituximab for biopsy-confirmed cAMR. The control group consisted of age- and race-matched patients who underwent donor-specific antibody-based protocol biopsies but had no rejection. We collected data on BK virus (BKV), cytomegalovirus (CMV), urinary tract infection (UTI), and pneumonia postbiopsy.

There were 49 patients in each group. In those with cAMR, 21 (43%) were treated with steroids, IVIG, and rituximab; the remaining received steroids and IVIG only. The risk of graft failure was greater in the cAMR group [22 (45%) vs. 3 (6%),

< 0.001]. Kaplan-Meier analyses demonstrated a significantly greater risk of pneumonia in the cAMR group (

= 0.02). This was confirmed by multivariable Cox regression analyses [Hazard ratio (HR) = 6.04,

= 0.027, 95% CI, 1.22-29.75]. None of the patients with pneumonia were affected by opportunistic pathogens. Additionally, the risk of CMV, UTI, and BKV was not increased. Rituximab was not independently associated with any of the infections studied.

Treatment of cAMR, but not rituximab, was associated with a 6-fold increased risk of pneumonia. Additional studies are needed to determine the safety and efficacy of prolonged antimicrobial prophylaxis and monitoring strategies, including for hypogammaglobulinemia, to reduce the risk of pneumonia following the treatment of cAMR.

Treatment of cAMR, but not rituximab, was associated with a 6-fold increased risk of pneumonia. Additional studies are needed to determine the safety and efficacy of prolonged antimicrobial prophylaxis and monitoring strategies, including for hypogammaglobulinemia, to reduce the risk of pneumonia following the treatment of cAMR.

Hepatic artery stenosis (HAS) following liver transplantation results in hypoperfusion and ischemic damage to the biliary tree. This study aimed to investigate how vascular intervention, liver function test derangement, and time point of HAS onset influence biliary complications.

A single-center retrospective study of adult patients that underwent primary liver transplantation. Patients were grouped according to the presence or absence of HAS and then into early (≤90 d) or late (>90 d) subgroups. Biliary complications comprised anastomotic (AS) or non ASs (NASs).

Computed tomography angiography confirmed HAS was present in 39 of 1232 patients (3.2%). This occurred at ≤90 and >90 days in 20 (1.6%) and 19 (1.5%), respectively. The incidence of biliary strictures (BSs) in the group with HAS was higher than the group without (13/39; 33% versus 85/1193; 7.1%,

= 0.01). BS occurred in 8/20 (40.0%) and 5/19 (26.3%) of the early and late groups, respectively. The need for biliary intervention increased if any liver function test result was ≥3× upper limit of normal (

= 0.019).

BS occurs at a significantly higher rate in the presence of HAS. Onset of HAS at ≤90 or ≥90 days can both be associated with morbidity. Significant liver function test derangement at HAS diagnosis indicates a higher likelihood of biliary intervention for strictures.

BS occurs at a significantly higher rate in the presence of HAS. Onset of HAS at ≤90 or ≥90 days can both be associated with morbidity. Significant liver function test derangement at HAS diagnosis indicates a higher likelihood of biliary intervention for strictures.

In October 2018, a new heart allocation policy was implemented with intent of prioritizing the sickest patients and decreasing waitlist time. We examined the effects of the new policy on transplant practices and outcomes 1 year before and 1 year after the change.

Transplant recipients from October 2017 to September 2019 at our institution were identified and divided into 2 cohorts, a preallocation and postallocation criteria change. Patient demographics, clinical data, and bridging strategy were assessed. Early outcomes including ischemic time, severe primary graft dysfunction, need for renal replacement therapy, and duration of hospital stay were investigated.

In the 12 months before the change, 38 patients were transplanted as compared to 33 patients in the 12 months after the change. The average wait-time to transplant decreased after the allocation change (49 versus 313 d,

= 0.02). Patients were more likely to be bridged with an intra-aortic balloon pump (45% versus 3%) and less likely to be supported with a durable left ventricular assist device (LVAD) after the change (24% versus 82%). There was an increase in total ischemic time after the change (177 versus 117 min,

≤ 0.01). There were no significant differences in other early posttransplant outcomes.

Implementation of the new allocation system for heart transplantation resulted in dramatic changes in the bridging strategy utilized at our institution. Temporary mechanical support usage increased following the change and the number of recipients supported with durable LVADs decreased. Early posttransplant outcomes appear similar.

Implementation of the new allocation system for heart transplantation resulted in dramatic changes in the bridging strategy utilized at our institution. Temporary mechanical support usage increased following the change and the number of recipients supported with durable LVADs decreased. Early posttransplant outcomes appear similar.

This is the first time deemed consent, where the entire population of a jurisdiction is considered to have consented for donation unless they have registered otherwise, will be implemented in North America. While relatively common in other regions of the world-notably Western Europe-it is uncertain how this practice will influence deceased donation practices and attitudes in Canada.

We describe a Health Canada funded program of research that will evaluate the implementation process and full impact of the deceased organ donation legislation and the health system transformation in Nova Scotia that includes opt-out consent.

There is a need to evaluate the impact of these changes to inform not only Nova Scotia and Atlantic Canada, but also other provincial, national, and international stakeholders.

We establish a rigorous academic framework that we will use to evaluate this significant health system transformation.

We establish a rigorous academic framework that we will use to evaluate this significant health system transformation.

Strategies to extend the pool of organs include and promote the use of segmental liver grafts. While performing a living donor left lateral segment (LLS) liver transplant and in split procedures, the hepatic artery´s division becomes critical when a dominant segment 4 artery (S4A) emerges from the left hepatic artery (LHA). We aim to describe a novel technique that consists of performing microsurgical reconstruction from the pyloric artery (PA) to S4A.

A 45-y-old living donor was evaluated to use his LLS as a graft for a pediatric recipient. During the procedure, a dominant S4A born from the LHA was dissected. To obtain an appropriate LHA length and diameter for the recipient, it was necessary to transect it. An extended right lobe split graft was used in a 61-y-old patient. The S4A born from LHA had to be sectioned during the split procedure. In both cases, segment 4 remained incompletely perfused. The PA was dissected with enough length to be rotated, to perform a microsurgical anastomosis to the S4A, recovering parenchyma’s color and Doppler signal while vascular permeability was demonstrated using CT scan. There was no biliary or cut surface complication.

PA to S4A reconstruction is a simple and novel technique that can be used for LLS and extended right lobe split graft and might contribute to increase donor selection and reduce living donor and recipient S4A-related complications.

PA to S4A reconstruction is a simple and novel technique that can be used for LLS and extended right lobe split graft and might contribute to increase donor selection and reduce living donor and recipient S4A-related complications.Oncolytic adenoviruses are being developed as new anti-cancer agents. Their efficacy can be improved by incorporating RNA interference (RNAi) molecules. RNAi molecules can be expressed in various precursor formats. The aim of this study was to determine the most effective format. To this end, we constructed three Δ24-type oncolytic adenoviruses, with human microRNA-1 (miR-1) expression cassettes in short hairpin RNA (shRNA), precursor microRNA (pre-miRNA), and primary miRNA (pri-miRNA) format, respectively. The viruses were compared for virus replication, mature miR-1 expression, and target gene silencing in cancer cells. Incorporation of the cassettes had only minor effects on virus replication. Mature miR-1 expression from the pri-miRNA format reached on average 100-fold higher levels than from the other two formats. This expression remained stable upon long-term virus propagation. Infection with the pri-miR-1-expressing virus silenced the validated miR-1 targets FOXP1 and MET. Drosha knockout almost completely abrogated mature miR-1 expression, confirming that processing of adenovirus-encoded pri-miR-1 was dependent on the host cell miRNA machinery. Using simple in vitro recombination cloning, a similar virus expressing miR-26b was made and shown to silence the validated miR-26b target PTGS2. We thus provide a platform for construction of oncolytic adenoviruses with high expression of RNAi molecules of choice.Oncolytic virotherapy relies on the induction of anti-tumor immune responses to achieve therapeutic efficacy. The factors that influence the induction of these responses, however, are not well understood. To begin to address this lack of knowledge, we asked how decreasing the susceptibility of malignant cells to direct viral infection would impact the induction of immune responses and therapeutic efficacy caused by oncolytic myxoma virus treatment. To accomplish this, we used CRISPR-Cas9 genome editing to remove the essential sulfation enzyme N-deacetylase/N-sulfotransferase-1 from B16/F10 murine melanoma cells. This eliminates the negative cell surface charges associated with glycosaminoglycan sulfation, which reduces a cell’s susceptibility to infection with the myxoma virus by ∼3- to 10-fold. With the use of these cells as a model of reduced susceptibility to oncolytic infection, our data demonstrate that 3- to 10-fold reductions in in vivo infection do not hinder the ability of the oncolytic myxoma virus to induce anti-tumor immunity and do not lower the overall efficacy of localized treatment. Additionally, our data show that in mice bearing multiple distinct tumor masses, the choice to treat a less-susceptible tumor mass does not reduce the overall therapeutic impact against either the injected or noninjected lesion. Taken together, these data suggest that minor changes in the susceptibility of malignant cells to direct oncolytic infection do not necessarily influence the overall outcomes of treatment.The authors consider theory in the animal-metacognition literature. Theoretical interpretation was long dominated by associative descriptions, as illustrated in the 2009 special issue. We suggest that this approach risks a self-limiting understanding of animal mind, and an imprecise understanding of the cognitive requirements inherent in metacognition tasks. In fact, some tasks self-entail the need for higher-level decision-making processes, processes that-in humans-we would call explicit, declarative, and conscious. These points are illustrated using the inaugural study on dolphin metacognition. We urge researchers to turn more toward illuminating the cognitive architecture of capacities like metacognition, including illuminating the depth, and structure, the learning/memory systems, the cognitive levels, and the declarative awareness possibly present in animals’ minds. The empirical development of this literature demonstrates that researchers are now prepared to do so. This study can produce strong synergies across the allied fields of biopsychology, comparative and cognitive psychology, and neuroscience.

Heart failure (HF) prognosis without therapy is poor, however introduction of a range of drugs has improved it. We aimed to perform a systematic review on the effects and safety of sodium-glucose transporter 2 inhibitors (SGLT2i) in HF patients.

We carried out a systematic review of randomized controlled trials (RCTs) on SGLT2i compared to placebo for HF patients. We searched in PubMed, Scopus, Web of Science and EMBASE, with no language restriction, from inception to 31 August 2020. We included nine RCTs comprising three arms (empagliflozin, dapagliflozin and placebo). Effects sizes for continuous variables were expressed as mean differences (MDs) and 95% confidence intervals (CIs). Effects sizes for dichotomous variables were expresses as risk ratio (RR) and 95% CIs. We used random-effect models with the inverse variance method. We performed subgroup meta-analyses by intervention drug and follow-up period.

SGLT2i significantly reduced all-cause mortality (RR 0.88, 95%CI 0.79-0.98, I2=0%), cardiovascular mortality (RR 0.87, 95%CI 0.77-0.99, I2=0%), HF hospitalization (RR 0.73, 95%CI 0.66-0.81, I2=0%) and emergency room visits due to HF (RR 0.40, 95%CI 0.21-0.76, I2=0%), as well as composite outcomes including the previous ones. Besides, it significantly improved the score of the Kansas City Cardiomyopathy Questionnaire (KCCQ, MD 1.70, 95%CI 1.67-1.73, I2=54%). SGLT2i reduced any serious adverse events, blood pressure and weight. However, it increased hematocrit and creatinine. The meta-analysis of RCTs of>12weeks of follow-up showed that SGTL2i significantly reduced NT-proBNP.

SGLT2i showed to improve critical outcomes in HF patients, and it is apparently safe.

SGLT2i showed to improve critical outcomes in HF patients, and it is apparently safe.