Notes

Effects of idiopathic flatfoot deformity about knee joint adduction times during walking.
After the operation, the patient did not receive chemo- or radiotherapy, and underwent an aggressive rehabilitation regiment. Follow up 10 months later, symptoms improved. To our best knowledge, this is the first case of concomitant IDH mutation and BRAF fusion in pediatric spinal cord astrocytoma.
To investigate whether exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, affects connexin 43 (Cx43) expression in osteoblasts, and determine the specific mechanism underlying Cx43 modulation by Ex-4.

Osteoblast-like MC3T3-E1 cells were treated with Ex-4 with or without GLP-1R antagonist. We assessed Cx43 expression using RT-PCR, western blotting, and confocal microscopy; visualized intercellular communication using Lucifer yellow dye transfer assay; evaluated osteoblast differentiation using alkaline phosphatase and Alizarin red S (ARS) staining. Cx43 silencing or overexpression was investigated via RNA-interference or adenovirus infection. The mechanism underlying Cx43 regulation by Ex-4 was determined via treatment with either Src kinase inhibitor, KX2-391, Akt activator, sc79, or inhibitor, LY294002.

Ex-4 treatment enhanced Cx43 expression and gap junctional intercellular communication in MC3T3-E1 cells. GLP-1R antagonist pretreatment abrogated the induction of Cx43 expression. Cx43 silencing significantly decreased ARS staining intensity in Ex-4-treated cells, whereas overexpression enhanced cell differentiation. Treatment with KX2-391 reduced both the Ex-4-induced increase of Cx43 expression and p-Akt protein levels. sc79 upregulated Cx43 expression, while LY294002 attenuated Cx43 upregulation by Ex-4.

Induced Cx43 expression in osteoblasts via the Src-Akt signaling pathway illustrates the underlying mechanism for promoting osteoblast differentiation by Ex-4.
Induced Cx43 expression in osteoblasts via the Src-Akt signaling pathway illustrates the underlying mechanism for promoting osteoblast differentiation by Ex-4.
BRAF mutations are present in up to 8% of human cancers, and comprise a viable therapeutic target in many patients harboring these mutations. Specific BRAF-targeted therapies, such as vemurafenib, dabrafenib, and encorafenib, have transformed treatment of many BRAF-mutated cancers, producing meaningful clinical benefit with more tolerable safety profiles compared to prior standard-of-care treatments. BRAF inhibitors were first approved for use in metastatic melanoma, although resistance almost always limited their long-term effectiveness. Combination therapy with BRAF and MEK inhibitors has proven effective in delaying the onset of resistance, and produces additional clinical benefit across cancers. Although not promising initially in treatment of BRAF-mutated colorectal carcinoma, BRAF inhibitors in colorectal cancer were successfully combined with EGFR inhibitors, resulting in significant treatment response. Refining the use of BRAF and MEK inhibitors in less common tumor types (and for non-V600 mutationsAlthough not promising initially in treatment of BRAF-mutated colorectal carcinoma, BRAF inhibitors in colorectal cancer were successfully combined with EGFR inhibitors, resulting in significant treatment response. Refining the use of BRAF and MEK inhibitors in less common tumor types (and for non-V600 mutations) and delaying the development of resistance remain pertinent future considerations in treating BRAF-mutated cancers. In this review, we will discuss the prevalence of BRAF mutations across human cancers and evidence on the efficacy and safety of current management strategies for various BRAF-mutant solid tumors.
The aim of the study was to evaluate the results of an all arthroscopic technique for the treatment of massive rotator cuff tears using the long head of biceps as a graft to reconstruct the superior capsule and to reinforce the cuff.

A retrospective review of a consecutive series of arthroscopic repair of massive rotator cuff tears using the long head of biceps tendon was conducted. Twenty-five patients underwent surgery, and none were lost at follow-up. Minimum follow-up period was more than 12months. Constant, UCLA and VAS scores as clinical outcome were analyzed. Time for surgical procedures was also registered. Two alternative procedures (transosseous or anchors) were employed to fix laterally the long head of biceps to the greater tuberosity and to reinforce the cuff. This choice was essentially determined by the bone quality of the greater tuberosity.

All patients of both groups (Transosseous 15 and Anchors 10) showed a significant improvement of clinical and functional scores. Difference of the operative times between two procedures was statistically significant in favor of the anchor approach. No intraoperative complications were recorded. Postoperative shoulder stiffness was found in two male patients. In no case biceps tenodesis was performed Popeye sign was easily detected in 16 patients but they did not complain any superior arm pain and weakness.

This technique represents a valid solution for treatment of massive rotator cuff tears resulting safe, easier and cost saving in comparison with other published techniques.
This technique represents a valid solution for treatment of massive rotator cuff tears resulting safe, easier and cost saving in comparison with other published techniques.Since the exports' nature and the productive capabilities of economies and regions play an essential role in driving the energy demand and carbon dioxide (CO2) emissions, the modern literature focuses on the importance of export composition in determining the environmental quality. For this purpose, this study aims to test the composition impact of the trade by using export product diversification, extensive margin, and intensive margin on energy use and environment in a case study for the ten newly industrialized countries (NICs) from 1970 to 2014. Additionally, this study employs some other indicators such as income, urbanization, and economic complexity during our investigations. The obtained results from different panel estimations demonstrate that not only the composition of export products but also the income, urbanization, and economic complexity promote energy use and CO2 emissions. The panel causality results revealed a bidirectional linkage between overall diversification and CO2 emissions, and the intensive margin and CO2 emissions. In contrast, a unidirectional causality ran from CO2 emissions to the extensive margin. Energy consumption presented a bidirectional causality with the overall diversification, intensive margin, economic complexity, and urbanization. Finally, a unidirectional causality is observed from energy consumption to the extensive margin. Based on findings, applicable policies are discussed.The abandoned Malachov deposit belongs among the most important historic Hg deposits in the world. The soil, groundwater, surface water, plants, and animals are still heavily contaminated by potentially toxic elements such as As and Cd, but mainly by Hg. This article is focused on the Hg contamination of aquatic plants and animals in the Malachov creek. Mercury concentrations were measured in fresh water (on average 3 µg L-1), in the zoobenthos (on average 362.47 µg kg-1), and in the phytobenthos (on average 578.36 µg kg-1). Higher Hg concentrations were determined in the muscles of Salmo trutta morpha fario (on average 362.47 µg kg-1) and lower in Cottus poecilopus (on average 352.75 µg kg-1). The Hg concentrations were higher in the internal tissues (578.36-1185.75 µg kg-1) than in the muscles of the fish. The Hg content in fresh water exceeded Regulation of the Slovak Government No. 269/2010, which stipulates the criteria for achieving a proper water balance, but the Hg content in the fish muscles of both fish species was below the specified limit of the Food Code of Governmental Regulation of the Slovak Republic No. 608/3/2004-100. The Hg contamination in fishes is controlled by their weight and age. The presented data may be used as the base information for future studies in order to be able to estimate consumption recommendations and warnings.Post-infarction remodeling is a clinical problem with no curative treatment. Our objective was to search for new biomarkers of cardiac remodeling that have clinical value after ST-segment elevation myocardial infarction (STEMI). This pilot study enrolled 67 consecutive patients with de novo STEMI who underwent revascularization by primary angioplasty. Echocardiography studies of cardiac function were completed during the first 48 h post-STEMI and after 6 months of follow-up. Galectin-3 and soluble receptor for advanced glycation end products (sRAGE) were tested in the peripheral venous blood during the 24 h post-infarction. Cardiac remodeling was defined as changes ≥ 15% in the left ventricular end-systolic volume (LVESV) or > 10% in the left atrial area (LAA). An inverse association was found between galectin-3 (rs = - 0.296; p less then 0.001) and sRAGE (rs = - 0.327; p less then 0.001) levels and the basal left ventricle ejection fraction (LVEF). However, only galectin-3 was directly associated with the increase in LVESV (rs = 0.389; p = 0.007) and LVEDV (rs = 0.314; p = 0.031) during the follow-up. sRAGE was inversely related to the change in LAA (rs = - 0.320; p = 0.032). These data are consistent with galectin-3, but not sRAGE levels, as a predictor of left ventricle remodeling (OR 1.036, 95% CI 1.002-1.071; p = 0.039). Galectin-3 and sRAGE levels that were measured during hospitalization are inversely related to basal LVEF after a STEMI. Galectin-3 levels are a predictor of adverse post-STEMI LV remodeling, whereas sRAGE levels exhibited an inverse relationship with left atrial remodeling. KEY MESSAGES Post-infarction remodeling is a clinical problem with no curative treatment. New biomarkers for remodeling after acute myocardial infarction were explored. Early post-STEMI galectin-3 and soluble RAGE are inversely related with left ventricle function. Galectin-3 levels were predictors of adverse post-STEMI left ventricle remodeling. Soluble RAGE levels were associated with left atrial remodeling.MicroRNAs (miRNAs) are non-encoding, single-stranded RNA molecules of about 22 nucleotides in length encoded by endogenous genes involved in posttranscriptional gene expression regulation. Studies have shown that miRNAs participate in a series of important pathophysiological processes, including the pathogenesis of depression. This article systematically summarized the research results published in the field of miRNAs and depression, which mainly involved three topics circulating miRNAs as markers for diagnosis and prognosis of depression, the regulatory roles of miRNAs in the pathogenesis of depression, and the roles of miRNAs in the mechanisms of depression treatment. By summarizing and analyzing the research literature in recent years, we found that some circulating miRNAs can be potential biomarkers for the diagnosis and prognostic evaluation of depression. miRNAs that disorderly expressed during the disease play important roles in the depression pathogenesis, and miRNAs also play roles in the mechanisms of psychotherapy and drug therapy for depression. Elucidating the important roles of miRNAs in depression will bring people's understanding of the pathogenesis of depression to a new level. In addition, these miRNAs may be developed as new biomarkers for diagnosing depression, or as drug targets, or these molecules may be used as new drugs, which may provide new means for the treatment of depression. KEY MESSAGES • The research results of miRNAs and depression are reviewed. • Circulating miRNAs can be potential biomarkers for depression. • MiRNAs play important roles in the depression pathogenesis. • MiRNAs play important roles in drug therapy for depression.Primary ovarian insufficiency (POI) is defined as a reduction in ovarian function before the expected age of menopause. POI is known to increase the risk of cardiovascular disorders, osteoporosis, cognitive decline, and mood disorders, resulting in a reduced quality of life. Appropriate hormone replacement for premenopausal women decreases these adverse health risks and improves quality of life for women with POI, but does not prolong life expectancy. The potential etiologies of POI include chromosomal abnormalities and genetic mutations, autoimmune factors, and iatrogenic causes, including surgery, chemotherapy, and radiation therapy. A major association is suggested to exist between reproductive longevity and the DNA damage pathway response genes. DNA damage and repair in ovarian granulosa cells is strongly associated with POI. Depletion of oocytes with damaged DNA occurs through different cell death mechanisms, such as apoptosis, autophagy, and necroptosis, mediated by the phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/forkhead transcription factors 3 (FOXO3) pathway. Mesenchymal stem cells (MSCs) are characterized by the ability of self-renewal and differentiation and play an important role in the regeneration of injured tissues. Transplantation of MSCs has been shown to functionally restore ovarian reserve in a POI mouse model. Recent advances in stem cell therapy are likely to be translated to new therapeutic options bringing new hope to patients with POI. The aim of this review is to summarize the pathogenic mechanisms that involve cell death and DNA damage and repair pathways and to discuss the stem cell-based therapies as potential therapeutic options for this gynecologic pathology.
The prognosis of metastatic gastric cancer has improved due to trastuzumab in patients with HER2 positive. Circulating tumor cells (CTCs) have been examined as a prognostic predictor in gastric cancer. The clinical advantage of trastuzumab was examined in gastric cancer patients with HER2-negative tumor tissues and HER2-positive CTCs.

A total of 105 patients with metastatic or recurrence gastric cancer were enrolled. All patients were examined HER2 expression in CTC using the CellSearch system in blood specimens.

CTCs were detected in 65 of 105 patients (61.9%) and 61 patients were divided into three groups Group A (n = 27), histological HER2-positive; Group B (n = 17), histological HER2-negative and HER2-positive CTCs; and Group C (n = 17), HER2-negative on histology and CTCs. Patients received capecitabine plus cisplatin. Groups A and B were additionally treated by trastuzumab. There was no relationship between tumor tissues and CTCs in HER2 expression. Even if group B had no histological HER2 expression, group B showed a good prognosis as same as group A, and group C had a significantly worse overall survival than groups A and B. The multivariate analysis demonstrated that HER2-expression on CTCs was an independent prognostic factor for both overall and progression-free survival.

The present results indicate the potential clinical utility of trastuzumab combined chemotherapy in patients with HER2-positive CTCs even if they are histologically HER2-negative.
The present results indicate the potential clinical utility of trastuzumab combined chemotherapy in patients with HER2-positive CTCs even if they are histologically HER2-negative.This study explores the role of family partners, peer professionals with lived experiences of raising a child with behavioral health needs, and their value in primary and community-care based mental health services for young children aged 0-8 years. Interviews and focus groups were conducted with staff, leadership, and caregiver participants (n = 38) from two early childhood mental health programs and analyzed using thematic analysis. Five interdependent themes emerged (1) the centrality of lived experience to the family partner role; (2) the importance of the family partner in family engagement and relationship building; (3) the value added by the family partner in navigating systems; (4) the ability of the family partner to build skills and empower caregivers; (5) the role of the family partner in alleviating caregiver stress and other mental health concerns. Adapting and expanding the role of family partners will improve effective mental health care for children and their caregivers.
To assess and compare the stability and outcomes of the two surgical approaches for patients with roll asymmetry.

A total of 50 adult patients were consecutively recruited for this prospective study. Patients with class III asymmetry and lip or occlusal cant who underwent bimaxillary surgery were grouped according to surgical approach asymmetric posterior impaction on both sides (API, n = 31) and posterior impaction on one side and posterior extrusion on the other side (PIE, n = 19). Postsurgical stability and outcomes between groups were determined with cone-beam computed tomography for facial midline, lip, and occlusal cant at 1 week (T1), and at least 12-month postsurgery (T2, completion of orthodontic treatment).

Presurgery, the upper anterior occlusal cant and lip cant were significantly greater for the PIE group (p < 0.05). Postsurgery (T2), the mandible moved upward and rotated upward in both groups. However, the upward rotation was significantly greater in the PIE group compared with the API group. Although the two approaches resulted in significant improvements in facial symmetry, the deviation in the facial midline remained under-corrected for most API patients.

Patient outcomes for mandibular stability and facial symmetry differed between the two surgical approaches for correction of class III asymmetry with lip or occlusal cant.

The findings of this study suggest that planned over-correction is a reasonable option for the approach of asymmetric posterior impaction on both sides.
The findings of this study suggest that planned over-correction is a reasonable option for the approach of asymmetric posterior impaction on both sides.
The aim of the investigation was to evaluate the maxillary alveolar bone morphology, bone architecture, and bone turnover in relation to the mechanical strain distribution in rats with dental premature contact.

Fifty 2-month-old male Wistar rats were used. The premature contact group (N=40) received a unilateral (right side) resin cementation on the occlusal surface of the upper first molar. The animals were distributed in 4 subgroups according to the periods of euthanasia 7, 14, 21, and 28 days after cementation (N=10, for each period). For the control group (N=10), the teeth were kept without resin, featuring a normal occlusion. The pieces including the upper first molars, alveolar bone, and periodontal tissue were processed to histological and immunohistochemical evaluation of RANK-L and TRAP protein expression. A three-dimensional bone microarchitecture analysis was performed, where the heads of animals were scanned using microtomography and analyzed using CT-Analyser software (Bruker, Kontich, Belgiubone microarchitecture, and histological and immunohistochemical analyses showed that a model with dental traumatic occlusion resulted in changes of alveolar bone mechanobiology and, consequently, its morphology.

These results could be applied in dental treatment planning bringing biological and mechanical feedback to provide an effective mechanism to obtain physiological bone loss responses. Furthermore, this association between experimental and computational analyses will be important to figure out the alveolar bone response to mechanical stimulation in different clinical conditions.
These results could be applied in dental treatment planning bringing biological and mechanical feedback to provide an effective mechanism to obtain physiological bone loss responses. Furthermore, this association between experimental and computational analyses will be important to figure out the alveolar bone response to mechanical stimulation in different clinical conditions.As SARS-CoV-2 stunned and overtook everyone's lives, multiple daily briefings, protocols, policies and incident command committees were mobilized to provide frontline staff with the tools, supplies and infrastructure needed to address the COVID-19 pandemic. Medical resources were immediately shifted. In light of the necessity for self-isolation, telemedicine was expanded, although there has been concern than non-pandemic disorders were being ignored. Ambulatory care services such as bone densitometry and osteoporosis centered clinics came to a near halt. Progress with fracture prevention has been challenged. Despite the prolonged pandemic and the consequent sense of exhaustion, we must re-engage with chronic bone health concerns and fracture prevention. Creating triaging systems for bone mineral testing and in person visits, treating individuals designated as high risk of fracture using fracture risk assessment tools such as FRAX, maintaining telemedicine, leveraging other bone health care team members to monitor and care for osteoporotic patients, and re-engaging our primary care colleagues will remain paramount but challenging. The pandemic persists. Thus, we will summarize what we have learned about COVID-19 and bone health and provide a framework for osteoporosis diagnosis, treatment, and follow-up with the extended COVID-19 pandemic. The goal is to preserve bone health, with focused interventions to sustain osteoporosis screening and treatment initiation/maintenance rates.
The current pharmacotherapy of bipolar depression often presents limited efficacy and increased risk for adverse events. N-acetylcysteine (NAC) has been suggested as potentially effective and well-tolerated adjunctive treatment for bipolar disorder (BD).

This systematic review and meta-analysis aimed to examine the efficacy of N-acetylcysteine, as an adjunctive therapy, for treating bipolar depression.

PubMed, Cochrane Library, Scopus databases, and grey literature were searched for studies retrieval. Randomized controlled trials including patients with a diagnosed bipolar disorder and a current depressive episode were included in the analysis. The measured variables included symptoms, functioning, and quality of life scales. The mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) was set as the primary outcome.

A total of five studies were included in the analysis. A significant improvement was not observed from the addition of NAC to standard therapy in symptomatology [MADRS (MD = -3.32; 95% CI = -12.79 to 6.16), Young Mania Rating Scale (MD=-0.7; 95% CI=-2.15 to 0.75), Bipolar Depression Rating Scale (MD=-3.19; 95% CI=-15.48 to 9.1), and Clinical Global Impression for severity (MD=-0.13; 95% CI=-0.33 to 0.08)], functioning, [Global Assessment of Functioning Scale (MD=3.21; 95% CI=-12.55 to 18.97), Social and Occupational Functioning Assessment Scale (MD=0.47; 95% CI=-4.60 to 5.53), or quality of life [Quality of Life Enjoyment and Satisfaction Questionnaire (MD=2.27; 95% CI=-9.13 to 13.67)].

There is no evidence indicating that NAC has beneficial effects as an adjunctive treatment for bipolar depression. Future trials with improved methodological design and efficient sample sizes are required to draw safer conclusions.
There is no evidence indicating that NAC has beneficial effects as an adjunctive treatment for bipolar depression. Future trials with improved methodological design and efficient sample sizes are required to draw safer conclusions.Approximately 90% of pediatric acute lymphoblastic leukemia (ALL) cases are curable with intensified chemotherapy, but very high-risk patients may require hematopoietic stem cell transplantation (HSCT). A suitable indication for HSCT in the first complete remission (CR1) should be defined to protect patients from long-term complications. We report the outcomes of HSCT in CR1 from the Japan Association of Childhood Leukemia Study (JACLS) ALL-02 study and reassess indications for HSCT. Of 1114 patients, 71 (6.4%) received HSCT in CR1. Indications included high-risk cytogenetic abnormalities and non-CR on day 33. Patients with B-cell precursor (BCP) ALL and a prednisolone poor response (PPR) received HSCT when leukocyte antigen-matched siblings were available. The 4-year overall survival (OS) of transplanted patients was 78.8% (confidence interval 67.3-86.6). Multivariate analysis revealed that cord blood transplantation was associated with poor OS. For BCP-ALL patients with PPR who achieved CR1 after induction therapy, HSCT in CR1 showed excellent outcomes (4-year OS 90.9%) but demonstrated no survival advantage as the outcome with chemotherapy was also excellent (4-year OS 97.0%). This study suggests that in BCP-ALL patients PPR is not an indication for HSCT in CR1. Precise evaluation of treatment responses would increase sophistication of indications for HSCT in CR1.
EGFR (epidermal growth factor receptor) mutant NSCLC (non-small cell lung carcinoma) comprises 35-40% of cases in the Asian NSCLC cohort, compared to 15-20% in the rest of the world. Improved response rates have been observed in terms of PFS (progression-free survival) and ORR (overall response rate) when treated with EGFR TKIs (tyrosine kinase inhibitors). However, resistance eventually ensues regardless of the generation of TKI used. Preclinical studies have reported that PDL1 (programmed death ligand1) is a downstream target of EGFR and is interposed by IL-6/JAK/STAT3 (interleukin-6/Janus kinase/signal transducer and activator of transcription3), NF-κB (nuclear factor kappa beta), and p-ERK1/2/p-c-Jun pathways. Hence, it may potentially be repressed by EGFR TKIs. In this retrospective exploratory analysis, we studied whether PDL1 expression affects efficacy of EGFR TKIs and clinical outcome in patients with untreated metastatic EGFR-mutated lung adenocarcinoma.

This single-center retrospective, explorassion in EGFR-mutated NSCLC does not have any prognostic significance. Also the efficacy of EGFR TKIs is not influenced by variations in PDL1 TPS.
The current study was an exploratory retrospective study; however, the results add to the growing body of evidence that PDL1 expression in EGFR-mutated NSCLC does not have any prognostic significance. Also the efficacy of EGFR TKIs is not influenced by variations in PDL1 TPS.
To evaluate the clinical feasibility of a newly developed mobile PET system with MR-compatibility (flexible PET; fxPET), compared with conventional PET (cPET)/CT for brain imaging.

Twenty-one patients underwent cPET/CT with subsequent fxPET/MRI using
F-FDG. As qualitative evaluation, we visually rated image quality of MR and PET images using a four-point scoring system. We evaluated overall image quality for MR, while we evaluated overall image quality, sharpness and lesion contrast. As quantitative evaluation, we compared registration accuracy between two modalities [(fxPET and MRI) and (cPET and CT)] measuring spatial coordinates. We also examined the accuracy of regional
F-FDG uptake.

All acquired images were of diagnostic quality and the number of detected lesions did not differ significantly between fxPET/MR and cPET/CT. Mean misregistration was significantly larger with fxPET/MRI than with cPET/CT. SUVmax and SUVmean for fxPET and cPET showed high correlations in the lesions (R = 0.84, 0.79; P < 0.001, P = 0.002, respectively). In normal structures, we also showed high correlations of SUVmax (R = 0.85, 0.87; P < 0.001, P < 0.001, respectively) and SUVmean (R = 0.83, 0.87; P < 0.001, P < 0.001, respectively) in bilateral caudate nuclei and a moderate correlation of SUVmax (R = 0.65) and SUVmean (R = 0.63) in vermis.

The fxPET/MRI system showed image quality within the diagnostic range, registration accuracy below 3mm and regional
F-FDG uptake highly correlated with that of cPET/CT.
The fxPET/MRI system showed image quality within the diagnostic range, registration accuracy below 3 mm and regional 18F-FDG uptake highly correlated with that of cPET/CT.Thoracic (pulmonary and thymic) neuroendocrine tumors are well-differentiated epithelial neuroendocrine neoplasms that are classified into typical and atypical carcinoid tumors based on mitotic index cut offs and presence or absence of necrosis. This classification scheme is of great prognostic value but designed for surgical specimens, only. Deep molecular characterization of thoracic neuroendocrine tumors highlighted their difference with neuroendocrine carcinomas. Neuroendocrine tumors of the lung are characterized by a low mutational burden, and a high prevalence of mutations in chromatin remodeling and histone modification-related genes, whereas mutations in genes frequently altered in neuroendocrine carcinomas are rare. Molecular profiling divided thymic neuroendocrine tumors into three clusters with distinct clinical outcomes and characterized by a different average of copy number instability. Moreover, integrated histopathological, molecular and clinical evidence supports the existence of a grey zone category between neuroendocrine tumors (carcinoid tumors) and neuroendocrine carcinomas. Indeed, cases with well differentiated morphology but mitotic/Ki-67 indexes close to neuroendocrine carcinomas have been increasingly recognized. These are characterized by specific molecular profiles and have an aggressive clinical behavior. Finally, thoracic neuroendocrine tumors may arise in the background of genetic susceptibility, being MEN1 syndrome the well-defined familial form. However, pathologists should be aware of rarer germline variants that are associated with the concurrence of neuroendocrine tumors of the lung or their precursors (such as DIPNECH) with other neoplasms, including but not limited to breast carcinomas. Therefore, genetic counseling for all young patients with thoracic neuroendocrine neoplasia and/or any patient with pathological evidence of neuroendocrine cell hyperplasia-to-neoplasia progression sequence or multifocal disease should be considered.
To provide a brief and focused review on peripheral neuroimmune interactions and their implications for some clinical disorders.

Narrative review of the literature including of English-language articles published between 1985 and 2021 using PubMed and MEDLINE.

Many studies on experimental models and in vitro indicate that there are close interactions between the neural and immune systems. Processes from sensory afferents and autonomic efferents co-localize with immune cells and interact at discrete anatomical sites forming neuroimmune units. These neuroimmune interactions are bidirectional and mediated by a wide range of soluble factors including neuropeptides, classical neurotransmitters, cytokines, and other molecules that mediate complex cross-talk among nerves and immune cells. Small-diameter sensory afferents express a wide range of receptors that respond directly to tissue damage or pathogen signals and to chemokines, cytokines, or other molecules released from immune cells. Reciprocally, immune civation.The release of heavy metals to the environment increased dramatically with industrialization and rapid economic development, and they have accumulated in aquatic organisms. The current study aimed toe valuate the physiological, immunological, and histological changes of crayfish (Procambarus clarkii) as bio-indicator for water quality. Crayfishes of the filed study group were collected from a polluted area (Rosetta branch, Egypt), where the highest concentration for heavy metals in water was for zinc (Zn). Besides the field study group, other crayfishes were exposed to different doses of ZnSO4 (0, 203, and 406 mg L-g) corresponding to Zn concentration (0, 46.03, and 92.06 mg L-1) respectively in aquariums for consecutive 4 days. Heavy metal concentrations in field water sample were arranged as follows Zn > Fe> Pb > Cu and Mn > Ni > Co > Cd. The result revealed that Zn bioaccumulation increases significantly with the increase of water Zn concentration among the tested groups compared to the control group, wherkia. We assumed that Procambarus clarkia could be used as a sensitive bioindicator for monitoring water quality criteria.Recent studies have been found that polyphenols from plums fruits can inhibit the proliferation of multiple cancer cells, while the molecular mechanism was unclear. This study aimed to investigate the molecular mechanism underlying the pro-apoptotic effect of purified plum polyphenols (PPP) on human lung cancer A549 cells. Quercitrin (quercetin-3-O-glucoside, 814.19 ± 40.71 mg/g) was identified as the primary polyphenol in PPP via ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS). PPP showed a strong capacity for inhibiting the proliferation of the A549 cells by inducing apoptosis, which was reflected by an increase in the Bax/Bcl-2 ratio. Additionally, the inhibitory rate of PPP on the A549 cells were higher than that of vitamin C when the treatment dose exceeded 160 μg/mL. Transcriptome analysis suggested that PPP-induced apoptosis was closely associated with regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/forkhead box protein O 1 (FOXO1) pathway in the A549 cells. Subsequently, as an activator of AKT, SC79 was applied to confirm that the inhibition of AKT phosphorylation play an important role in the PPP-induced apoptosis of the A549 cells. These results illustrated the potential of PPP as a dietary compound for the prevention of cancer or for use during chemotherapy.Learning through work is a common feature of preparing health professionals for practice. Current understandings of work-integrated learning or a 'work-based placement', focus on students being consumers of experiences rather than providing a reciprocal benefit to the organisation in which they are placed. More nuanced understanding of the ways that students can offer value to organisations may provide new opportunities and increased capacity for workplace learning. This study drew on Social Exchange Theory to explore the perceived value and benefits of work-integrated learning experiences to the organisations in which students are placed. The focus was on population health placements undertaken by dietetics students at a large Australian university. An interpretive approach was employed with interviews with placement educators and document analysis of student-generated products from their placement. Seventeen of 20 eligible placement educators were interviewed, with interview data coded using thematic framework analysis. These data were supported with document analysis of student scientific posters completed as part of assessment to develop themes which were interpreted with social exchange theory. Three themes were identified (1) students add to the organisation's capacity, (2) benefits outweigh time cost of planning and supervising and (3) explicitly valuing students for their contributions may build trust and further potentiate bi-directional benefits. Results suggest that student placements can add value to organisations. This reciprocity of benefits should be communicated to all stakeholders involved in the university-community collaboration, including students. Social exchange theory sensitised researchers to nuanced findings that may support the translation of these study findings to other student work-integrated learning settings.The aim of this review was to determine the role of surgery in treating hypothalamic hamartoma (HH) causing isolated central precocious puberty (CPP). Literature review was done according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Patients with isolated CPP due to HH, managed with surgical resection, were included. We found 33 studies, reporting 103 patients (76 pedunculated, 27 sessile). Patients were considered "cured" if the symptoms of PP had regressed and the hormone profile had normalized after surgery. Indications for surgery included hamartoma deemed surgically resectable (n-12), for the purpose of tissue diagnosis (n-3), partial response/failure of preoperative therapy (n-9), and unable to afford/to avoid long-term medical therapy (n-7). The extent of resection was total (TR) (n-39), near total/subtotal (NTR/STR) (n-20), partial (PR) (n-35), or unspecified (n-9). On follow-up (range 3 months-16 years), 73.6% (56/76) of patients with pedunculated HH were cured, while 17.1% (13/76) had partial relief. Only 3/27 (11.1%) of patients with sessile HH were cured. All patients with a pedunculated hamartoma who underwent TR (n=36) improved, with 88.88% cured of the symptoms. Surgery had no effect in 17/23 (73.9%) patients with sessile HH who underwent PR. Psychological symptoms improved in 10/11 patients. There was no mortality. Permanent complications, in the form of 3rd nerve palsy, occurred in 3.7% (2/54) of the patients. To conclude, in the current era of availability of GnRH analogs, surgical resection in a subset of patients may be acceptable especially for small pedunculated hamartomas.Retinitis pigmentosa (RP) is a group of genetically diverse inherited disorders characterised by the progressive photoreceptors and pigment epithelial cell dysfunction leading to central vision impairment. Although important advances in the understanding of the pathophysiologic pathways involved in RP have been made, drug delivery for the treatment of ocular disorders affecting the posterior segment of the eye is still an unmet clinical need. In the present study, we describe the development of multi-loaded PLGA-microspheres (MSs) incorporating two neuroprotectants agents (glial cell-line-derived neurotrophic factor-GDNF and Tauroursodeoxycholic acid-TUDCA) as a potential therapeutic tool for the treatment of RP. A solid-in-oil-in-water (S/O/W) emulsion solvent extraction-evaporation technique was employed for MS preparation. A combination of PLGA and vitamin E was used to create the microcarriers. The morphology, particle size, encapsulation efficiency and in vitro release profile of the MSs were studied. En6.66% of the initial multi-loaded formulation). These optimised microparticles exhibited sustained in vitro releases over 91 days. These results suggest that the microencapsulation procedure optimised in this work presents a promising technological strategy for the development of multi-loaded intraocular drug delivery systems (IODDS).
[
Ga]Ga-PSMA-11 PET/CT allows for a superior detection of prostate cancer tissue, especially in the context of a low tumor burden. Digital PET/CT bears the potential of reducing scan time duration/administered tracer activity due to, for instance, its higher sensitivity and improved time coincidence resolution. It might thereby expand [
Ga]Ga-PSMA-11 PET/CT that is currently limited by
Ge/
Ga-generator yield. Our aim was to clinically evaluate the influence of a reduced scan time duration in combination with different image reconstruction algorithms on the diagnostic performance.

Twenty prostate cancer patients (11 for biochemical recurrence, 5 for initial staging, 4 for metastatic disease) sequentially underwent [
Ga]Ga-PSMA-11 PET/CT on a digital Siemens Biograph Vision. PET data were collected in continuous-bed-motion mode with a mean scan time duration of 16.7min (reference acquisition protocol) and 4.6min (reduced acquisition protocol). Four iterative reconstruction algorithms were applied usinollow-up.Recurrent pericarditis is a true challenge for clinicians, especially when the patient becomes unresponsive or not tolerant to conventional treatments. An accurate diagnosis of recurrent pericarditis, possibly supported by advanced imaging tools, is critical to provide timely and appropriate treatment of symptoms and prevention of further episodes. The incessant research on the inflammatory pathways underlying cardiovascular diseases, led recently to the assessment of anti interleukin-1 agents in the setting of recurrent pericarditis. This review will focus on the diagnostic assessment of recurrent pericarditis, along with the most modern therapeutic advances in this field. Bibliographic databases were searched (MEDLINE/PubMed, BioMed Central, the Cochrane Collaboration Database of Randomized Trials, Scopus, ClinicalTrials.gov, EMBASE, Google Scholar) using the terms "recurrent pericarditis" AND "diagnosis" OR "treatment" OR "IL-1" OR "inflammation".
This study aimed to investigate the efficiency and safety of tranexamic acid use in open reduction and internal fixation of pelvis and acetabulum fractures.

73 consecutive patients were included. 1000mg TXA was administered intravenously to all patients before surgery. The patients were evaluated on the basis of preoperative, postoperative first and third day hemoglobin-hematocrit values, amount of drainage collected, total blood loss, transfusion rates and complications.

Mean operative time was 120.1min. Average decrease in hematocrit levels between preoperative and postoperative first day was 2.1g/dL. Average collected blood from the drain was 177mL. Mean total blood loss was 1137mL. Transfusion rate of the patients was 21%. Mean transfused units was 0.9 units. Three patients died within 3 weeks after the operation due to myocardial infarction, acute kidney failure and pneumonia. There were no cases of symptomatic venous or pulmonary thromboembolism during the 90days of follow-up.

Use of TXA in pelvic and acetabular fractures was found to be effective in reducing total blood loss, hemoglobin drop and transfusion rates without increasing venous and pulmonary thromboembolism in our series.
Use of TXA in pelvic and acetabular fractures was found to be effective in reducing total blood loss, hemoglobin drop and transfusion rates without increasing venous and pulmonary thromboembolism in our series.
Malignant peripheral nerve sheath tumors (MPNSTs) are rare mesenchymal neoplasms that represent a profound therapeutic challenge due to their high proclivity for recurrence and metastasis and relatively poor response to systemic therapy regimens. While our understanding of the pathophysiology of MPNST is growing, including loss of the tumor suppressor gene neurofibromin and subsequent activation of the Ras pathway, targeted therapy to modify the poor prognosis seen in MPNST patients has thus far been without success. Correspondingly, MPNST patients are treated as per soft tissue sarcoma treatment algorithms with anthracycline-based therapy as the front-line therapy of choice for patients with unresectable, locally advanced, or metastatic MPNST. Beyond first-line anthracycline-based therapy, other standard cytotoxic chemotherapy agents used in advanced MPNST include the alkylating agent ifosfamide and the topoisomerase II inhibitor etoposide. Notably, soft tissue sarcoma regimens are used in MPNST despite di clinical trials.The histone modifications usually form complicated networks to regulate accessibility of DNA and transcription. Identification of proteins that are involved in the crosstalk among different histone modifications will help to better understand the epigenetic regulatory network in eukaryotes. The Inhibitor of Growth (ING) proteins represent a tumor suppressor family were first linked to histone modification in yeast and their functions in epigenetic regulation were further characterized. This review summarizes the crosstalk of histone modification in fungi and describes recently achieved mechanistic insights into the role of Fng1 (an ING protein in filamentous ascomycetes) in this process. We conclude that Fng1 is involved in crosstalk among histone acetylation, deacetylation and methylation.Describe the incidence of invasive pneumococcal disease (IPD) in serotypes with reduced antibiotic sensitivity to penicillin (RAS-Pen) in adults over 59 years of age and its association with childhood anti-pneumococcal vaccination coverage (CVC) and community consumption of beta-lactam. We selected IPD cases in adults over 59 years of age reported in the Community of Madrid between 2007 and 2016. We estimated the incidence of cases caused by serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13), those not included (non-PCV13) and the six serotypes additional to the 7-valent (PCV13-no7). We compared the incidences of serotypes from the pre-vaccine period (2007-2009) and the vaccine period (2011-2016) by analysing the incidence trend (JointPoint Trend Analysis) and its association with the CVC and community consumption of beta-lactam (Poisson model). We identified 1936 cases of IPD, 29.2% (n = 565) in serotypes with RAS-Pen. The incidence decreased for PCV13 cases (annual percentage of change, APC -12.2, p 59 years was decreasing and was associated with CVC. The incidence of cases due to non-PCV13 was increasing and was associated with community consumption of beta-lactam.Quorum sensing (QS) is a method of inter-cellular communication that permits bacteria to dispense information about cell density and to synchronize the gene expression accordingly. Gram-positive and Gram-negative bacteria utilize distinct quorum sensing mechanisms for effective pathogenesis. Virulence factor production by pathogenic bacteria is one of the important traits that is under the control of QS. A growing body of evidence has indicated the role of the nutritional environment notably by carbohydrates in dictating the QS-associated virulence gene regulation. The modulation of QS by carbohydrates mitigates the survival and establishment of the pathogen within its host which in turn leads to an increase in morbidity and mortality. This mini-review throws light on the predilection of pathogenic bacteria to rapidly regulate its QS-linked virulence gene expression based on the changing nutrient levels that assist them in prospering within diverse niches.During studies to investigate the health of mangrove trees in South Africa, high numbers of Avicennia marina were found with leaf galls caused by unidentified adults and larvae of midges (Cecidomyiidae). Fungal fruiting structures were commonly observed on the abaxial areas of the galls. To determine the identity of the fungi associated with the gall midges, phylogenetic analyses using multigene sequence data were used. The nuclear large subunit (LSU), internal transcribed spacer (ITS), and a portion of the actin gene region (ACT), were amplified and analyzed. The results revealed that the fungal fruiting structures represent a new taxon in the Mycosphaerellaceae described here as Zasmidium mangrovei sp. nov. This is the first report of a species in the Mycosphaerellaceae associated with cecidomyiid leaf galls on A. marina.Intravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0-1 and 0-2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI 1.29-1.82, I2 0%) or favorable outcome (adjusted OR=1.68, 95% CI 1.31-2.15,I2 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI 2.76-28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI 0.12%-1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.Rabbit haemorrhagic disease virus (RHDV) was recovered from necropsied rabbits that died during an outbreak characterized by epistaxis, incoordination, paralysis, and multi-organ haemorrhages in Ilorin, Nigeria. The haemagglutination test (HA) and RT-PCR assay targeted against a fragment of the RHDV VP60 gene were performed on liver, spleen, and kidney homogenates; faeces; and urine obtained from the rabbits. Amplicons were purified, sequenced, and phylogenetically analysed. The liver homogenates yielded the highest HA titres while RT-PCR of liver, spleen, and kidneys yielded the expected 1252 bp band. Sequence and phylogenetic analyses revealed that the Nigerian RHDV strain (RHDV/NGR/ILN/001) was 98.57%, 97.95%, and 96.70% homologous with RHDV2 (RHDVGI.2) strains from the Netherlands, Germany, and France, respectively. RHDV/NGR/ILN/001 induced tracheal, intestinal, and mediastinal lymph node haemorrhages, pulmonary oedema and congestion, and enlarged, necrotic liver in experimentally inoculated rabbits. The implications of this study, which is the first report of RHDV in Nigeria, are discussed.The two-electron reduction potential for a set of 393 flavin derivatives is presented in this article. These derivatives are substituted flavin on carbon 6, 7, 8, and 9 by coinage transition metals (Cu, Ag, and Au) and conjugated double bond hydrocarbons; and both groups are examined with and without functional groups such as OH, Cl, CH3, COOH, and NO2. In order to show the validity of the results, the reduction potential of human life molecules, which have experimental values, such as flavin adenine dinucleotide (FAD) and riboflavin (vitamin B2) is calculated. The experimental value for FAD is - 0.22 V, while the obtained theoretical value is - 0.21 V, and the corresponding values for riboflavin are - 0.18 and - 0.19 V, respectively. Theoretical calculations have been carried out by DFT procedure with a 6-31+G** basis set and BLYP xc-functional for coinage transition metals substitution, and MPW1PW9 xc-functionals for conjugated double bond hydrocarbon substitution. Both xc-functionals are chosen by the DFT calibration procedure.
This study uses a large-population national database to describe the presenting clinical, sociodemographic, treatment, and clinical outcome differences between pediatric and adult craniopharyngiomas.

This study utilized the 2004-2015 National Cancer Database and was queried for all cases of craniopharyngioma. Multivariate Cox proportional-hazards analysis was used to determine clinical and sociodemographic factors associated with mortality. Kaplan-Meier log-rank test determined differences in overall survival (OS) time.

The cohort consisted of 3638 patients, with 816 (22.4%) pediatric (≤ 18 years) patients. Pediatric patients presented with significantly higher frequency of large tumors (> 3 cm, 54.1 vs. 31.8%, p < 0.001), lower frequency of papillary subtype (0.9 vs. 11.5%, p < 0.001), and were exclusively treated at academic centers (100 vs. 73.4%, p < 0.001). Pediatric patients had significantly higher rates of adjuvant radiation (34.3 vs. 22.3%; p < 0.001), and had significantly lower 90-day mortality (1.
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