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Medicine is expeditiously evolving, and the number of diagnostic opportunities has increased exponentially in the last decade. Electronic medical records (EMRs) have been welcomed in most institutions worldwide following an early period of suspicious behavior. Unfortunately, several cracks dictated the initial approach to hospital systems and leadership incompetency. However, the pathway for a successful decade of EMRs is paved. This narrative review illustrates some principles implementing Epic Beaker software for anatomic pathology in academic medical institutions. Implementing such software improves the diagnostic approach in the division of anatomic pathology because the pathologists can directly access an enormous amount of clinical and radiological information now at their front desk using extremely versatile windows.

Viral respiratory diseases (VRDs) cause lung inflammation and inflammatory cytokine production. We study whether dapsone is responsible for its observed preventive treatment effects of the sustained viral RNA interferon response. Around 2008 and 2012, Korea’s Dementia Management Act stipulated drastic changes in the administration of dementia medication by medical staff. Participants were randomized and we compared leprosy patients with VRDs after prescribing dapsone as a standard treatment from 2005 to 2019. Significance was evaluated based on the dapsone-prescribed (+) subgroup and the dapsone-unprescribed (−) subgroup of the VRD diagnosed (+) and VRD undiagnosed (−) subgroup. We analyzed VRD ( +)/(− with dapsone (+)/(−) group and used a T-test, and designed the equation of acetylation with dapsone and acetylcholine (AA) equation. The 6394 VRD participants who received the dapsone intervention compared to the 3255 VRD participants in the control group demonstrated at T2 VRD (+) dapsone (−) (mean (M) = 224.80, SD = 97.50): T3 VRD (−) dapsone (+) (M = 110.87, SD = 103.80), proving that VRD is low when dapsone is taken and high when it is not taken. The t value is 3.10, and the p value is 0.004395 (significant at p r(15) = −0.823189, p = 0.005519, and with COPD, r(15) = −0.8161, p = 0.000207 (significant at p

Purpose of review Sarcoidosis is a chronic granulomatous disorder involving multiple systems and organs of undefined etiology. Although most of the morbidity relies upon lung disease, the function of several systems and organs can be affected. The natural history of lung disease consists of pulmonary involvement. An exaggerated and abnormal inflammatory response accompanies this aspect. There are noncaseating confluent epithelioid granulomas and, potentially, a progressive airway obstruction ab externo. As the disease is multisystemic, there is an increased likelihood of complications that may be serious and even fatal. Recent findings The American Thoracic Society (ATS) Core Curriculum updates clinicians annually in adult and pediatric lung disease, critical medical care, and sleep medicine. In late 2020, the ATS targeted sarcoidosis. Also, in 2019, the French Sarcoidosis Group thoroughly revised the literature on pediatric sarcoidosis. Currently, staging is based on chest radiograph findings, and the most commonly used system is the Scadding classification, which has been applied to both children and adults alike. Treatment may consist of oral or pulsed intravenous corticosteroids, but it should be implemented in union with a rheumatologist, as there are no randomized controlled studies in children. Summary Sarcoidosis is rare in childhood. Diagnosis is complex and relies on multiple diagnostic modalities with both staging and therapy progressively mirroring the sarcoidosis, which affects adults. In the majority of patients, spontaneous resolution will occur and observation is justified above treatment. Nevertheless, in case treatment is needed corticosteroids remain the mainstay of the treatment in some pediatric patients. Relapses are not uncommon and a long-term follow-up is essential.

The last two years have shown many political and scientific debates during the current Coronavirus Disease 2019 (COVID-19) pandemic [...]

The major clinical problem in human cancer is metastasis. Metastases are the cause of 90% of human cancer deaths. TAp63 is a critical suppressor of tumorigenesis and metastasis. ΔNp63 acts as a dominant-negative inhibitor to block the function of p53 and TAp63. Although several ubiquitin E3 ligases have been reported to regulate p63 stability, the mechanism of p63 regulation remains partially understood. Herein, we show that CHIP, an E3 ligase with a U-box domain, physically interacts with p63 and promotes p63 degradation. Notably, Hsp70 depletion by siRNA stabilizes TAp63 in H1299 cells and destabilizes ΔNp63 in SCC9 cells. Loss of Hsp70 results in a reduction in the TAp63-CHIP interaction in H1299 cells and an increase in the interaction between ΔNp63 and CHIP in SCC9 cells. Our results reveal that Hsp70 acts as a molecular switch to control CHIP-mediated ubiquitination and degradation of p63 isoforms. Furthermore, regulation of p63 by the Hsp70-CHIP axis contributes to the migration and invasion of tumor cells. Hence, our findings demonstrate that Hsp70 is a crucial regulator of CHIP-mediated ubiquitination and degradation of p63 isoforms and identify a new pathway for maintaining TAp63 or ΔNp63 stability in cancers.

Pirh2 is an E3 ligase belonging to the RING-H2 family and shown to bind, ubiquitinate and downregulate p73 tumor suppressor function without altering p73 protein levels. AIP4, an E3 ligase belonging to the HECT domain family, has been reported to be a negative regulatory protein that promotes p73 ubiquitination and degradation. Herein, we found that Pirh2 is a key regulator of AIP4 that inhibits p73 function. Pirh2 physically interacts with AIP4 and significantly downregulates AIP4 expression. This downregulation is shown to involve the ubiquitination of AIP4 by Pirh2. Importantly, we demonstrated that the ectopic expression of Pirh2 inhibits the AIP4–p73 negative regulatory pathway, which was restored when depleting endogenous Pirh2 utilizing Pirh2-siRNAs. We further observed that Pirh2 decreases AIP4-mediated p73 ubiquitination. At the translational level and specifically regarding p73 cell cycle arrest function, Pirh2 still ensures the arrest of p73-mediated G1 despite AIP4 expression. Our study reveals a novel link between two E3 ligases previously thought to be unrelated in regulating the same effector substrate, p73. These findings open a gateway to explain how E3 ligases differentiate between regulating multiple substrates that may belong to the same family of proteins, as it is the case for the p53 and p73 proteins.

Background: Dapsone is helpful in the molecular regulation of inflammasome activation, ubiquitin, one/two-electron oxidation, ubiquitination cascade, and myeloperoxidase/halide system. Objective: To study whether lung inflammation, inflammatory cytokine production, viral RNA, and sustained interferon (IFN) response by dapsone are responsible for its observed preventive treatment effects, functioning as a competitor against viral diseases. Methods: We compared Hansen's disease (HD) patients with viral respiratory diseases (VRDs) after prescribing dapsone as a standard treatment from 2005 to 2019. Results: The 3705 VRD participants who received the dapsone intervention compared to the 1172 VRD participants in the control group demonstrated T2 (M = 269.88, SD = 88.70, 95% CI 266.13-273.62, p-value < .00001):T3 (M = 59.75, SD = 93.36, 95% CI 51.36-68.14, p-value < .00001) definitely proves that VRD is very low when dapsone is taken, and very high when not taken. The t-value is −3.42, and the p-value is 0114. (significant at p < 0.05). It demonstrated significantly more prevalence of VRD in the DDS unprescribed group. We designed the Factor consisting of the dapsone taking group and anti-Alzheimer's disease drug (AAD) taking Alzheimer's disease (AD) diagnosed group, and it was strongly negatively correlated with the prevalence of Bronchitis and chronic obstructive pulmonary disease (COPD). It means that dapsone treated and AAD exacerbated them, but both had nothing to do with Pneumonia.Conclusion: This study provides theoretical clinical data that dapsone prevents and treats viral respiratory diseases and their related Bronchitis and COPD during the pandemic; moreover, AAD should be stopped.

An intriguing form of hepatitis has been detected in more than a hundred children worldwide [...]

In the last couple of decades, biomarkers have been on the rise for diagnostic and predictive value. There has been a rush to identify new markers using new technologies and drug repurposing approaches. SMARCB1 acronym arises from the SWI/SNF (SWItch/Sucrose Non-Fermentable)-related Matrix-associated Actin-dependent Regulator of Chromatin subfamily B member 1 (SMARCB1). It is a molecule, whose role is associated with the sucrose metabolism. SMARCB1 is also called INI1 (Integrase Interactor 1). The molecule was discovered in the mid-1990s. Its role as a loss-of-function marker for malignant rhabdoid tumors (MRT) of renal and extrarenal origin has enormously expanded the spectrum of involved neoplasms since that time. Several tumors have been characterized by genetic aberrations in the SMARCB1 gene. They include reduction in expression, loss of expression, and mosaic expression. Most of the tumors are sarcomas, but a variegated group of tumors with mixed phenotypes has also been delineated. It is well known that the outcome of patients harboring genetic aberrations in the SMARCB1 gene has been poor. Guo et al. reported that reduced SMARCB1 expression occurred in 70% of osteosarcomas. Their data significantly correlated with poor neoadjuvant response. These authors emphasize a shorter progression-free and overall survival of the patients demonstrating an altered expression of this gene. Interestingly, mRNA in silico analysis established that SMARCB1 expression correlates with the response to chemotherapy of osteosarcoma patients, but there was no reliable correlation between SMARCB1 expression level and metastasis, response to neoadjuvant therapy, overall survival, and progression-free survival. The study involved a tissue microarray (TMA) on bone tumors that may limit the full evaluation of the gene expression. Nevertheless, Guo et al.’s study is remarkable. It expands the list of the tumors harboring an altered SMARCB1 gene expression and suggests that this marker should be investigated in every pathology workup for potential predictive value. On the other side, much work needs to be done if we hope that we strive to provide additional therapeutic strategies for osteosarcoma patients with altered SMARCB1 gene expression.

Background: In the last decade, the proposed Cancer Stem Cell (CSC) hypothesis has steadily changed the way cancer treatment is approached. CSCs may be the source of the heterogeneous non-tumorigenic cell population included in a neoplasm. Intratumor and intertumoral heterogeneity is a well-known phenomenon that massively entangles the diagnosis and treatment of cancer. The literature seems to suggest that heterogeneity develops progressively within tumor-initiating stem cells. CSCs harbor genetic and/or epigenetic alterations that allow them to differentiate into multiple tumor cell types sequentially. Objective: The CSC hypothesis, cellular therapy, and the most recent patents on CSCs were reviewed. Methods: PubMed, Scopus, and Google Scholar were screened for this information. Also, an analysis of the most recent data targeting CSCs in pediatric cancer developed at two Canadian institutions is provided. The genes involved with the activation of CSCs and the drugs used to antagonize them are also highlighted. Results: It is underlined that (1) CSCs possess stem cell-like properties, including the ability for self-renewal; (2) CSCs can start carcinogenesis and are responsible for tumor recurrence after treatment; (3) Although some limitations have been raised, which may oppose the CSC hypothesis, cancer progression and metastasis have been recognized to be caused by CSCs. Conclusions: The significant roles of cell therapy may include an auto-transplant with high-dose treatment, an improvement of the immune function, creation of chimeric antigen receptor T cells, and the recruitment of NK cell-based immunotherapy.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a global pandemic that has affected over 7 million people worldwide, resulting in over 400,000 deaths. In the past 20 years, they have been several viral epidemics that were primarily transmitted by respiratory droplets. The use of face masks is proven to be effective in protecting health-care workers as they perform their duties. Still, there is limited evidence about whether the widespread use of face mask would be very useful in protecting the general population. This study aimed to conduct a review to determine if face masks would be beneficial in the general population as a means of reducing the spread of COVID-19. The widespread implementation of wearing face masks by the general population is challenging due to a variety of factors. However, the extensive use of cloth masks in conjunction with other preventative measures such as social distancing and handwashing can potentially reduce the risk of transmission of COVID-19.

Kefir consumption has been demonstrated to improve lipid and cholesterol metabolism; however, our previous study identified that benefits vary between different commercial and traditional kefir. Here, we investigate the ability of pitched culture kefir, that is, kefir produced by a small number of specific strains, to recapitulate health benefits of a traditional kefir, in a diet-induced obesity mouse model, and examine how microbial composition of kefir impacts these benefits. Eight-week-old female C57BL/6 mice were fed a high-fat diet (40 % energy from fat) supplemented with one of five kefir varieties (traditional, pitched, pitched with no Lactobacillus, pitched with no yeast and commercial control) at 2 ml in 20 g of food for 8 weeks prior to analysis of plasma and liver lipid profiles, and liver gene expression profiles related to lipid metabolism. Both traditional and pitched kefir lowered plasma cholesterol by about 35 % (P = 0·0005) and liver TAG by about 55 % (P = 0·0001) when compared with commercial kefir despite no difference in body weight. Furthermore, pitched kefir produced without either yeast or Lactobacillus did not lower cholesterol. The traditional and pitched kefir with the full complement of microbes were able to impart corresponding decreases in the expression of the cholesterol and lipid metabolism genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase, PPARγ and CD36 in the liver. These results demonstrate that traditional kefir organisms can successfully be utilised in a commercial process, while highlighting the importance of microbial interactions during fermentation in the ability of fermented foods to benefit host health.

Heritable thrombophilia is a category of genetic disorders of the coagulation cascade with the increasing risk of thrombus formation and recurrent pregnancy loss (RPL). Factor V Leiden (FVL) (R506Q) mutation is the most common genetic cause of deep venous thrombosis, but its association with RPL has been inconsistent in studies arising from non-Western countries. The present metanalysis was aimed to determine whether an association exists between FVL and RPL in the Middle East. We searched PubMed, MEDLINE Web of Science, Scopus, and Embase, evaluating the association between the FVL and RPL. The Middle East countries (Bahrain, Cyprus, Egypt, Iran, Iraq, Israel, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, The State of Palestine, Syria, Turkey, The United Arab Emirates, and Yemen) were evaluated in succession. Raw data were extracted, and 19 case–control studies were included in our final analysis. Overall, 2513 cases and 1836 controls in the Middle East showed a prevalence of FVL mutation as 12.6% and 4.9% in patients and controls, respectively. To evaluate the relationship between FVL mutation and RPL, we used Forest plot (random effect model) with the overall random OR of 2.37 (CI 95%: 1.50–3.75). FVL mutation was associated with a higher risk of RPL. In Iran, the OR was 1.90 (95% CI 1.04–3.45), and in Turkey, the OR was 3.01 (95% CI 1.10–8.23). The results of our study support an association between FVL mutation status and RPL in women of the Middle East countries. It is recommended that specific policies include comprehensive testing for FVL mutation as a standard of care in women of the Middle East region with unexplained RPL.

Osteosarcoma affects both adolescents and adults, and some improvement in the survival rate for affected patients has been reached in the last decade. Still, non-specificity and systemic toxicity may limit traditional therapeutic approaches to some extent. The insulin growth factor 1 (IGF1) and its binding protein (IGFBP3) have been implicated in the tumorigenesis. Nanoparticles, such as graphene oxide (GO), can provide an effective treatment for cancer as they can specifically target cancer cells while reducing undesired side effects. This study aimed to evaluate the toxicity of GO on osteosarcoma in vitro using tumor cell lines with and without knocking out the IGF and IGFBP3 genes. Human osteosarcoma cell lines, U2OS and SAOS2, and the normal osteoblast cell line hFOB1.19 were used. The IGF1 and IGFBP3 genes were eliminated using CRISPR/Cas9. Tumor cells were cultured and treated with GO. Apoptosis and reactive oxygen species (ROS) were analyzed by Annexin V-FITC and ROS assays. The nuclear factor erythroid 2-related factor 2 (NRF2), which is a crucial regulator of cellular resistance to oxidants, was investigated by Western blotting. We found a significantly higher rate of apoptosis in the OS than hFOB1.19, especially in U2OS cells in which IGF1 and IGFBP3 were knocked out. ROS increase due to GO exposure was remarkably time and concentration-dependent. Based on the rate of apoptosis, ROS, Nrf-2 decrease, and cytomorphological changes, GO has a significant cytotoxic effect against OS. Targeting the IGF1 and IGFBP3 signaling pathway may strengthen GO-related cytotoxicity with the potential to increase the survival of patients affected by this tumor.

This study investigated leprosy patients with Alzheimer's disease (AD) treated with dapsone (4,4’-diaminodiphenyl sulfone, DDS) as a cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway and neuroinflammasome competitor. We searched the Sorokdo National Hospital medical records and the National Health Insurance Service in South Korea with the International Classification of Diseases (ICD)-10 code and Electronic Data Interchange (EDI) from January 2005 to June 2020. Four groups were defined: Treatment (T) 1: DDS prescription (+) AD prevalence (+), T 2: DDS (+) AD nondiagnosed (-), T 3: DDS nonprescription (-) AD (+), T 4: DDS (-) AD (-). The T1:T3 tests demonstrate that the incidence of AD is significantly reduced in the presence of dapsone among AD patients. The T1:T3 tests demonstrate that the incidence of AD is significantly reduced in the presence of dapsone among AD patients. T1 (M = 0.18, SD = 0.074):T2 (M = 0.55, SD = 0.14) and T3 (M = 0.18, SD = 0.074):T4 (M = 0.55, SD = 0.14) explain that dapsone effects on AD can be clearly distinguished according to its presence or absence.The T1:T4 and the T2:T3 test demonstrate a causal relationship in which the presence or absence of dapsone determines the onset of AD. The T1:T3 test proved that the incidence of AD was significantly reduced by dapsone. (The t-value is -23.1, p-value is < .00001, significant at p < .05) The T2:T3 test proved that the prevalence of AD was significantly high without dapsone, and without AD was increased with dapsone. (The t-value is -6.38, p-value is < .00001, significant at p < .05) AD is increased in the absence of dapsone. Our study has demonstrated that dapsone has the potential for the prevention of AD. This study indicates that dapsone is a valid preventive therapeutic for AD. KEYWORD: Neuroinflmmasome, Alzheimer's disease, Dapsone

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces various systemic coronavirus diseases 2019 (COVID-19). Its pathophysiologies involve 1 the angiotensin-converting enzyme 2 (ACE2) and toll-like receptor 4 (TLR4) pathway, 2 Neuropilins (NRPs) Pathway, 3 The sterile alpha motif (SAM) and histi-dine-aspartate domain (HD)-containing protein 1 (SAMHD1) tetramerization pathway 4 Inflammasome ac-tivation pathways, 5 Cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) (cGAS–STING) signaling pathway, 6 Spike protein pathway, and 7 Immunological memory en-gram pathway. COVID-19 exacerbates immune-mediated diseases whose metabolisms use 1. ACE2, TLR4 in the brain, 2. SAMHD1 tetramerization and cGAS–STING-NLRP3 signaling, 3. inflammasome–spike protein–genetic activation, and 4. innate lymphoid cells (ILCs) with NRPs. Immune triad: Aspirin, Dapsone, and Dexamethasone to treat COVID-19 have worked harmoniously with modulating ILCs. Therefore, it is necessary to prescribe this triad to alleviate and block the pathologic course due to diverse and subsequent SARS-CoV-2 variants.

In the last couple of decades, we have experienced increased use of nutraceuticals worldwide with a demand for organic foods, which has been elevated to an extent probably unmatched with other periods of our civilization. One of the nutraceuticals that gained attention is epigallocatechin gallate (EGCG), a polyphenol in green tea. It has been suggested that diseases of the central nervous system can benefit from consuming some antioxidants, despite current results showing little evidence for their use in preventing and treating these diseases. ECGC may be beneficial in delaying the neurodegeneration of the substantia nigra regardless of the origin of Parkinson's disease (PD). This review covers the effect of EGCG on vitro and animal models of PD, the potential mechanisms of neuroprotection involved and summaries recent clinical trials in human PD. This review also aims to provide an investigative analysis of the current knowledge in this field and to identify putative crucial issues. Environmental factors such as dietary habits, drug use and social interaction are all factors that influence the evolution of neurodegenerative diseases. Therefore, the use of nutraceuticals requires further investigation.

Rubella is a highly contagious viral disease with a significant teratogenic effect. Various results have been published about the seroprevalence of rubella in Iran. A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-systematic review and meta-analysis were conducted to assess the immunity against rubella in Iranian women.Eleven English and Persian electronic databases including PubMed, ScienceDirect, Scopus, Web of Science, Google Scholar, Embase, Scientific Information Database, Iran doc, Iran Medex, Magiran, and Medlib were searched using the keywords: Epidemiology, Prevalence, Rubella, Women, Childbearing age, Reproductive age, and Iran. A mathematician (NS) reviewed all steps for accuracy.Out of 1,520 articles, 25 well-conducted studies with a total amount of 10,145 women were reviewed. The pooled prevalence rate of anti-rubella IgG was 84% (95% CI: 83%-86%). The highest prevalence rate of IgG was in Zahedan, Rasht, and Arak (each 100%), while the lowest prevalence was in Jahrom (54%). Subgroup analysis showed that from 1989 through 2012, the IgG prevalence rate increased from 78% (95% CI: 73-83%) to 99% (95% CI: 98 100%).Although the vaccination program seems working in Iran, some peripheral regions may be a target to improve health care policies.

Background: Dapsone is helpful in the molecular regulation of Nod-like receptor family pyrin domain-containing 3 (NLRP3).Objective: To study the targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by Dapsone should be responsible for its observed preventive treatment effects, functioning as a competitor against Pandemic viral inflammasome.Methods: We compared Hansen's disease (HD) patients with viral respiratory diseases (VRD) after prescribing Dapsone to standard treatment from 2005 to 2020. Results: The 3022 VRD participants who received the dapsone intervention (M = 201, SD = 34) compared to the 3961 VRD participants in the control group (M = 264, SD = 84) demonstrated significantly better peak flow scores, t(28) = -2.7, p = .01. It demonstrated significantly more prevalences of VRD in the DDS unprescribed group. Conclusion: This study is theoretical clinical data to warrant a pilot study with Dapsone for deteriorating leprosy patients at Pandemic.

Bile is a lipid-rich sterile solution produced in the liver that can be infected resulting in bactibilia. A higher incidence of postoperative infectious complications has been seen in patients with bactibilia. Recently, gram-negative bacteria have been linked to a tumor-associated inflammatory status. This study is a retrospective cohort study of 39 patients, who are over 80 years of age only (53.85% males and 46.15% females), hospitalized with diseases of the biliopancreatic system in one teaching hospital in Italy from January 2011 to December 2012 with a follow-up of 5 years. The most common biliary diseases after surgery were pancreatic head cancer (p

Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BCa) in which estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) are not expressed. Although TNBC cases account for approximately 15% of all BCa cases, TNBC patients' prognosis is poor compared with that of other BCa subtypes. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays an important role in cell proliferation and migration by negatively regulating the PI3K/Akt pathway. PTEN is one of the most commonly inactivated tumor suppressors in BCa. PTEN inactivity is associated with larger tumor sizes, multiple lymph node metastases, and an aggressive triple-negative phenotype. This review primarily focuses on two key points: (1) PTEN and its function. (2) The regulation of tumor suppressor PTEN in TNBC. We provide a summary of genomic alterations of PTEN in BCa. We further discuss the transcriptional regulation of PTEN and how PTEN is regulated by posttranscription and posttranslational modification, as well as by protein interactions. Finally, we discuss the perspectives of the PTEN protein in TNBC.

An imbalance between protein aggregation and protein degradation may induce ‘stress’ in the functionality of the endoplasmic reticulum (ER). There are quality control (QC) mechanisms to minimize misfolding and to eliminate misfolded proteins before aggregation becomes lethal for the cell. Proper protein folding and maturation is one of the crucial functions of the ER. Chaperones of the ER and folding enzymes guarantee correct conformational maturation of emerging secretory proteins. Histone deacetylase (HDAC) 6 (HDAC6) is a masterpiece coordinating the cell response to protein aggregate formation. The balance between HDAC6 and its partner Valosin-containing protein/p97 determines the fate of polyubiquitinated misfolded proteins. WT161 is a terrific, selective, and bioavailable HDAC6 inhibitor. WT161 selectively inhibits HDAC6 and adequately increases levels of acetylated α-tubulin. This compound induces accumulation of acetylated tubulin and cytotoxicity in multiple myeloma (MM) cells. In this journal, Sun et al. (Biosci. Rep.41, DOI: 10.1042/BSR20203905) identified that WT161 suppresses the cell growth of osteosarcoma cells. This discovery opens the door to future chemotherapeutic regimens of this bone neoplasm.

Background: Giardiasis is an important cause of waterborne and foodborne diarrhea, daycare center outbreaks, and traveler's diarrhea. Objective: The study aimed to provide an update on the evaluation, diagnosis, and treatment of giardiasis. Methods: A PubMed search was completed in Clinical Queries using the key terms “giardiasis”, "Giardia lamblia", "Giardia duodenalis" and "Giardia intestinalis". The search strategy included metaanalyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to the English literature. Patents were searched using the key term “giardiasis” from www.freepatentsonline.com. Results: Giardiasis is caused by the protozoan parasite Giardia lamblia. The parasite is transmitted by the fecal-oral route, frequently through ingestion of contaminated water and food or person-to person transmission. Risk factors for infection include children in day-care settings, child-care workers, institutionalized individuals, travelers in endemic areas, ingestion of contaminated or recreational water, immunodeficiency, cystic fibrosis, and oral-anal sex. Approximately 50 to 75% of infected children are asymptomatic. Other children present acute or chronic diarrhea. Direct fluorescent antibody tests that detect intact organisms, enzyme immunoassays that detect soluble antigens, and multiplex real-time polymerase chain reaction assays that detect specific genes of the parasite in stool samples have improved sensitivity and specificity compared with microscopic examination of stool specimens for the detection of Giardia trophozoites or cysts. Drugs used in the treatment of symptomatic giardiasis are reviewed in this study. Moreover, recent patents related to the management of giardiasis are also discussed. Conclusion: Metronidazole, tinidazole, and nitazoxanide are drugs of choice. Resistance to common antigiardial drugs has increased in recent years, therefore, the search for new molecular targets for antigiardial drugs is urgently needed. In general, treatment of asymptomatic carriers is not recommended. Purification of water supply is an important preventive measure.

Background and Aim Congenital segmental intestinal dilatation (CSID) is a neonatal condition with unclear etiology and pathogenesis. Typically, the newborn with CSID presents with a limited (circumscribed) bowel dilatation, an abrupt transition between normal and dilated segments, neither intrinsic nor extrinsic perilesional obstruction, and no aganglionosis or neuronal intestinal dysplasia. We aimed to review this disease and the long-term follow-up at the Children's Hospital of the Medical University of Innsbruck, Tyrol, Austria. Study Design Retrospective 25-year review of medical charts, electronic files, and histopathology of neonates with CSID. Results We identified four infants (three girls and one boy) with CSID. The affected areas included duodenum, ileum, ascending colon, and sigmoid colon. Noteworthy, all patients presented with a cardiovascular defect, of which two required multiple cardiac surgical interventions. Three out of the four patients recovered completely. To date, the three infants are alive. Conclusion This is the first report of patients with CSID and cardiovascular defects. The clinical and surgical intervention for CSID also requires a thorough cardiologic evaluation in these patients. CSID remains an enigmatic entity pointing to the need for joint forces in identifying common loci for genetic investigations.

Background: The gut microbiota play an essential role in protecting the host against pathogenic microorganisms by modulating immunity and regulating metabolic processes. In response to environmental factors, microbes can hugely alter their metabolism. These factors can substantially impact the host and have potential pathologic implications. Particularly pathogenic microorganisms colonizing pancreas and biliary tract tissues may be involved in chronic inflammation and cancer evolution. Purpose: To evaluate the effect of bile microbiota on survival in patients with pancreas and biliary tract disease (PBD). Patients and Methods: We investigated 152 Italian patients with cholelithiasis (CHL), cholangitis (CHA), cholangiocarcinoma (CCA), gallbladder carcinoma (GBC), pancreas head carcinoma (PHC), ampullary carcinoma (ACA), and chronic pancreatitis (CHP). Demographics, bile cultures, therapy, and survival rates were analyzed in cohorts (T1 death

Background Clinicians considered DDS administration to treat SARS-CoV-2 inflammasome. DDS is helpful in the molecular regulation of Nod-like receptor family pyrin domain-containing 3 (NLRP3).Objective To study the targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by DDS must be responsible for its observed preventive effects, functioning as a competitor.Methods This is a randomized controlled trial (RCT). We set out to use objective criteria of improvement. We treated the patients with standard Covid-19 acute respiratory distress syndrome (ARDS) treatment with DDS. The RCT results were analyzed.Results ARDS progression was blocked in 17 of 19 total patients at the first period. The 44 subjects were analyzed during the second period. It is significant at the ARDS onset stage. The mortality of ARDS-onset patients was 0% with DDS and 40% without DDS among the total of 65 cases. The t-value of RCT is -1.5, and the p-value is .075475. The result is significant at p Conclusion There was a significant difference in DDS treatment results in the ARDS-onset group. We confirmed that DDS clinically treated the onset of ARDS by targeting SARS-CoV-2-activated inflammasomes. Like chemically reacting substances, inflammasome and DDS compete, proving that it is effective in early ARDS.ClinicalTrials.gov Identifier: NCT04918914

Background Clinicians in critical care medicine considered dapsone administration to treat SARS-CoV-2 inflammasome. Dapsone is useful in the molecular regulation of Nod-like receptor family pyrin domain-containing 3 (NLRP3). Objective To study the targeting of NLRP3 itself or up-/downstream factors of the NLRP3 inflammasome by dapsone must be responsible for its observed preventive effects, functioning as a competitor. Methods This is case series with or without intervention; a cross-sectional study. We set out to use objective criteria of improvement, such as A. a reduction in the FIO2 requirement and B. a decrease in the progression of hypoxia. We treated the patients with standard COVID-19 ARDS treatment with dapsone 100 mg to target NLRP3 inflammasomes. Results The 22 cases were treated with standard COVID-19 therapy with dapsone (trial group), and the 22 cases were the control group. The comparison was made assuming that only decreased FIO2 was influential in the trial and control groups, which applied to only the ARDS onset stage. The chi-square statistic is 5.1836. The p-value is .02280. Fisher’s exact test statistic value is 0.0433. (The result is significant at p

Acute and chronic liver failure can be tackled using liver transplantation. Graft dysfunction is still a challenge in 21st century. It affects up to one-third of the recipients, notwithstanding good to excellent long-term outcome have been reported. At the time of the writing of this chapter, the etiologic investigation of the organ dysfunction has revealed a multifactorial background. Despite the multifactorial causes, ischemia and reperfusion (I/R) injury is probably the most important contributing factor for organ dysfunction. Cholestasis, i.e., the stoppage or reduction of bile flow with or without bile duct loss or ductopenia and biliary ductular proliferations are frequent accompanying factors in I/R injury. However, they can be misleading, and they can also be present in other graft dysfunction conditions. Biliary marker levels increase usually as early as 5 days after transplantation. In this chapter, we reviewed a liver transplantation model as I/R injury model to study in detail the intermediate filaments of the cytoskeleton. We indicate that the phenotypic switch of the hepatocytes occurs earlier than frank cholestasis. We suggest that targeting this phenotypical switch of the liver cells may contribute to the savage or better outcome of the liver graft.

Background: Neonates on long-term parenteral nutrition (PN) may develop parenteral nutrition-associated liver disease (PNALD). Aluminum (Al) is a known contaminant of infant PN, and we hypothesize that it substantially contributes to PNALD. In this study, we aim to assess the impact of Al on hepatocytes in a piglet model. Methods: We conducted a randomized control trial using a Yucatan piglet PN model. Piglets, aged 3-6 days, were placed into two groups. The high Al group (n=8) received PN with 63 µg/kg/day of Al, while the low Al group (n=7) received PN with 24 µg/kg/day of Al. Serum samples for total bile acids (TBA) were collected over two weeks, and liver tissue was obtained at the end of the experiment. Bile canaliculus morphometry was studied by transmission electron microscopy (TEM) and Image-J software analysis. In December 2019, the American Academy of Pediatrics issued a key technical report on Al effects in infants and children. This report was revised and commented on in this chapter. Results: The canalicular space was smaller, and the microvilli were shorter in the high Al group than in the low Al group. There was no difference in the TBA between the groups. Conclusions: Al causes structural changes in the hepatocytes despite unaltered serum bile acids. High Al in PN is associated with short microvilli, which could decrease the functional excretion area of the hepatocytes and impair bile flow. Long-term toxicity studies from the Al content in PN components supported the US Food and Drug Administration (FDA) in the decision to implement specific rules. It has been required that large-volume ingredients reduce the Al concentration and all small volume components be specifically labeled with the Al concentration. However, both US FDA and we consider that despite these rules, the total Al concentration from some components remains above the recommended final concentration. US FDA and our concerns about toxicity from the Al present in infant PN formulas are grounded, requiring more research on this topic.

Ex situ heart perfusion (ESHP) is being investigated as a method for the continuous preservation of the myocardium in a semiphysiologic state for subsequent transplantation. Most methods of ESHP position the isolated heart in a hanging (H) state, representing a considerable departure from the in vivo anatomical positioning of the heart and may negatively affect the functional preservation of the heart. In the current study, cardiac functional and metabolic parameters were assessed in healthy pig hearts, perfused for 12 hours, in either an H, or supported (S) position, either in nonworking mode (NWM) or working mode (WM). The cardiac function was best preserved in the S position hearts in WM (median 11 hour cardiac index (CI)/1 hour CI%: working mode perfusion in supported position = 94.77% versus nonworking mode perfusion in supported position = 62.80%, working mode perfusion in H position = 36.18%, nonworking mode perfusion in H position = 9.75%; p0.001). Delivery of pyruvate bolus significantly improved the function in S groups, however, only partially reversed myocardial dysfunction in the H heart groups. The hearts perfused ex situ in a semianatomical S position and in physiologic WM had better functional preservation and recovery than the H hearts in non-S position. Optimizing the positional support for the ex situ-perfused hearts may improve myocardial preservation during ESHP.

Hepatocellular carcinoma is one of the most common causes of cancer-related death worldwide. In cases of liver resection for hepatocellular carcinoma, the dissector, whether a pathologist’s assistant, physician, or resident, must have a clear understanding of both the terminology of liver anatomy and the requirements of the corresponding College of American Pathologists Cancer Protocol to properly orient, describe, dissect, and sample the specimen. This chapter provides guidance for the gross dissection procedure for the production of a valuable pathology report, which is of key importance for a patients’ ongoing care.

Radiologic and pathologic features of common and/or critical tumor or tumor-like diagnoses (lesions) of the liver are discussed within. Hepatocellular lesions (focal nodular hyperplasia, hepatocellular adenoma, hepatocellular carcinoma, and hepatoblastoma), biliary lesions (mucinous cystic neoplasm and intrahepatic cholangiocarcinoma), vascular mesenchymal lesions (cavernous hemangioma, epithelioid hemangioendothelioma, and hepatic angiosarcoma), and metastatic malignancies are the primary focus, although a more comprehensive list of lesions is also provided. Definitions, distributions, gross appearances and microscopic pathological features are introduced first, followed by radiologic correlation. Multiple imaging modalities are explored with an emphasis on those that provide the greatest value for the lesion under evaluation. A common understanding of the features of both diagnostic specialties will allow for high-quality correlation and subsequent high-quality patient care. Representative images highlighting important features are also presented.

Liver tumors are a heterogeneous and complex mix of benign and malignant neoplasms that may arise in the setting of chronic liver injury or due to no prior insult. In children, hepatoblastoma is the most common malignant primary liver tumor and hepatocellular carcinoma is rare. In adults, however, hepatocellular carcinoma is most common and undifferentiated embryonal sarcoma is vanishingly rare. Liver Cancer explores these, and the myriad of other entities in between, with a depth and precision that is highly informative and practical to the modern physician scientist. Descriptions of grossing techniques, histopathologic features, ancillary testing modalities, molecular/genetic abnormalities, imaging characteristics, treatment options, clinical signs/symptoms and surgical approaches are contemporary contributions to this exciting field. Liver Cancer represents the latest knowledge of primary liver tumors. Refreshingly, it focuses on tumors and underlying processes that affect both children and adults. Written by and for practicing Pathologists, Oncologists, Surgeons, Gastroenterologists and Radiologists, its comprehensive content makes it a valuable reference for primary liver tumors.

Ex situ heart perfusion (ESHP) is being investigated as a method for the continuous preservation of the myocardium in a semiphysiologic state for subsequent transplantation. Most methods of ESHP position the isolated heart in a hanging (H) state, representing a considerable departure from the in vivo anatomical positioning of the heart and may negatively affect the functional preservation of the heart. In the current study, cardiac functional and metabolic parameters were assessed in healthy pig hearts, perfused for 12 hours, in either an H, or supported (S) position, either in nonworking mode (NWM) or working mode (WM). The cardiac function was best preserved in the S position hearts in WM (median 11 hour cardiac index (CI)/1 hour CI%: working mode perfusion in supported position = 94.77% versus nonworking mode perfusion in supported position = 62.80%, working mode perfusion in H position = 36.18%, nonworking mode perfusion in H position = 9.75%; p < 0.001). Delivery of pyruvate bolus significantly improved the function in S groups, however, only partially reversed myocardial dysfunction in the H heart groups. The hearts perfused ex situ in a semianatomical S position and in physiologic WM had better functional preservation and recovery than the H hearts in non-S position. Optimizing the positional support for the ex situ-perfused hearts may improve myocardial preservation during ESHP.

Alzheimer’s Disease (AD) is pathologically characterized by the accumulation of soluble oligomers causing extracellular beta-amyloid deposits in form of neuritic plaques and tau-containing intraneuronal neurofibrillary tangles in brain. One proposed mechanism explaining the formation of these proteins is impaired phagocytosis by microglia/macrophages resulting in defective clearance of soluble oligomers of beta-amyloid stimulating aggregation of amyloid plaques subsequently causing AD. However, research indicates that activating macrophages in M2 state may reduce toxic oligomers. NEU1 mutation is associated with a rare disease, sialidosis. NEU1 deficiency may also cause AD-like amyloidogenic process. Amyloid plaques have successfully been reduced using NEU1.Thus, NEU1 is suggested to have therapeutic potential for AD, with lysosomal exocytosis being suggested as underlying mechanism. Studies however demonstrate that NEU1 may activate macrophages in M2 state, which as noted earlier, is crucial to reducing toxic oligomers. In this review, authors discuss the potential therapeutic role of NEU1 in AD via immune system.

Objective This study aimed to provide an extensive overview of clinical and pathological findings along with various therapeutic options analyzing in addiction, retrospectively, the surgical outcomes of a single center cohort. Background Thymic neoplasms are rare thoracic tumors which commonly are located in the anterior mediastinum and are associated with a wide spectrum of clinical presentations. They may run an indolent course or could present a very aggressive biologic progression with infiltration of mediastinal structures and presence of distant metastases. The pathogenesis of these tumors is so far not completely clear. Several treatment modalities in a multidisciplinary setting have to be considered in order to provide the best treatment for patients affected by thymic tumors. Methods We conducted a retrospective cohort analysis of all patients who underwent surgery due to thymic tumor in a university hospital located in Switzerland (Bern University Hospital) and then we performed a narrative review of the English literature using PubMed, Embase, Cochrane Database of Systematic Reviews and Scopus. Conclusions Minimally invasive techniques play an important role in the treatment of thymic tumors. A careful patients selection in a multidisciplinary setting is mandatory in order to offer the best treatment for patients affected by thymic tumors.

A covid-19 committee at Hunt regional Medical centre reviewed the use of Dapsone use as an off label medication based upon treatment adjuncts and inflammasome thesis. It recommends that any physician can write this prescription. However, to ensure safe, appropriate, and accurate administration. Following general guidance is recommended.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seems to be difficult to overcome. A pandemic of such a scale has not been seen since the 1918 influenza pandemic. Although the predominant clinical presentation is respiratory disease, neurological manifestations and sequelae are increasingly being recognized. We observed a case series of rapid recovery of ARDS within 24 h in the preliminary clinical features of COVID-19 ARDS-associated neurological disease. It was also noted that by 15 April, 2021, there was no SARS-CoV-2 ARDS on Sorok Island in South Korea, where lepers had been living together. We compared each of dapsone’s effects on humans and considered those of SARS-CoV-2. Dapsone showed different effects in the brain. The Sorokdo National Hospital reported a relationship between dapsone and the neuroinflammasome of Alzheimer’s disease (AD) in Sorok Island from January 2005 to June 2020. AD prevalence was low in the leprosy patient group who took dapsone regularly. The preliminary cross-sectional study of the trial group (22 subjects) and the control group (22 subjects) in the Hunt Regional Hospital reported the following results: The chi-square statistic is 5.1836. The p-value is 0.022801. The result is considered significant at p < 0.05. The results from the medical treatment from 21 December to 29 December 2020 were considered. The mortality rates at the ARDS onset stage were 0% with dapsone administered as a standard COVID-19 treatment and 40% without dapsone administered as a standard COVID-19 treatment, respectively. Based on the respiratory failure and sudden high death rate originating from the involvement of the brainstem, especially the pre-Bötzinger complex, dapsone can be used to significantly reduce the incidence of the cases of acute respiratory distress syndrome and other illnesses caused by SARS-CoV-2.

The recent pandemic of coronavirus infectious illness 2019 (COVID19) triggered by SARS-CoV-2 has rapidly spread around the globe, generating in severe events an acute, highly lethal pneumonia and death. In the past two hitherto similar CoVs, the severe acute respiratory syndrome CoV (SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV) also gained universal attention as they produced clinical symptoms similar to those of SARS-CoV-2 utilizing angiotensin-converting enzyme 2 (ACE2) receptor and dipeptidyl peptidase 4 (DPP4) to go into the cells. COVID-19 may also present with overtly neurological symptoms. The proper understanding of the expression and dissemination of ACE2 in central and peripheral nerve systems is crucial to understand better the neurological morbidity caused by COVID-19. Using the STRING bioinformatic tool and references through text mining tools associated to Coronaviruses, we identified SAMHD1 as the probable link to neurological symptoms. Paralleled to the response to influenza A virus and, specifically, respiratory syncytial virus, SARS-CoV-2 evokes a response that needs robust induction of a subclass of cytokines, including the Type I and, obviously, Type III interferons as well as a few chemokines. We correlate ACE2 to the pathogenesis and neurologic complications of COVID-19 and found that SAMHD1 links to NF-κB pathway. No correlation was found with other molecules associated with Coronavirus infection, including ADAR, BST2, IRF3, IFITM3, ISG15, MX1, MX2, RNASEL, RSAD2, and VPRBP. We suggest that SAMHD1 is the molecule that may be behind the mechanisms of the neurological complications associated with COVID-19.

Heart conditions in which the tricuspid valve (TV) faces either increased volume or pressure stressors are associated with premature valve failure. Mechanistic studies to improve our understanding of the underlying pathophysiology responsible for the development of premature TV failure are lacking. Due to the inability to conduct these studies in humans, an animal model is required. In this manuscript, we describe the protocols for a novel chronic recovery infant piglet heart model for the study of changes in the TV when placed under combined volume and pressure stress. In this model, volume loading of the right ventricle and the TV is achieved through the disruption of the pulmonary valve. Then pressure loading is accomplished through the placement of a pulmonary artery band. The success of this model is assessed at four weeks post intervention surgery through echocardiography, intracardiac pressure measurement, and pathologic examination of the heart specimens.

Background Infective endocarditis (IE) is an uncommon disease with an involved interplay of clinical and surgical team management. We aimed to define diagnosis parameters and delineate in-hospital management in patients with IE admitted in a tertiary hospital of Southern Italian. Materials and methods Fifty-six consecutive patients (42 males, 14 females; age range: 34-85 years) admitted for IE in the Infectious Diseases, Cardiac Surgery, and Cardiology units, between January 2011 and August 2017, were enrolled. Demographic data, mortality, comorbidities, specimen type, microscopy results, special histological staining performed, and antimicrobial therapy were collected and analyzed. Any comments at the multidisciplinary team meetings were recorded in minutes of and approved. Results We found 83.9% of patients with positive blood cultures. The four most common bacteria were methicillin-resistant Staphylococcus aureus (MRSA: 21.3%), methicillin-sensitive Staphylococcus aureus (MSSA: 17%), Streptococci (14.9%), and Enterococci (14.9%). Both in the univariate and multivariate analysis, we observed a significant positive correlation between surgery and complications. Particularly in the univariate analysis only, surgery was positively correlated to males and C-reactive protein (CPR) at baseline. Also, considering the most common bacteria, it resulted in a positive correlation between surgery and MRSA and Streptococci spp. and between complications and MSSA. Finally, the male gender was positively correlated to MSSA and heart complications, major arterial embolism, septic pulmonary emboli, splenic infarction, and cerebral embolism. Conclusions A blood culture test remains a critical factor for the diagnosis of IE and the antibiotic treatment of susceptible and emerging resistant bacteria. Male gender and heart complications are red flags for prompt operative management.