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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.

Background: Brain tumors are the second most common neoplasm in the pediatric age. Pesticides may play an etiologic role, but literature results are conflicting. This review provides a systematic overview, meta-analysis, and IARC/WHO consideration of data on parental exposure to pesticides and childhood brain tumors. Methods: We searched PubMed, SCOPUS, and Google Scholar for literature (1 January 1966–31 December 2020) that assessed childhood brain tumors and parental exposure to pesticides. We undertook a meta-analysis addressing prenatal exposure, exposure after birth, occupational exposure, and residential exposure. A total of 130 case-control investigations involving 43,598 individuals (18,198 cases and 25,400 controls) were included. Results: Prenatal exposure is associated with childhood brain tumors (odds ratio, OR = 1.32; 95% CI: 1.17–1.49; I2 = 41.1%). The same occurs after birth exposure (OR = 1.22; 95% CI: 1.03–1.45, I2 = 72.3%) and residential exposure to pesticides (OR = 1.31; 95% CI: 1.11–1.54, I2 = 67.2%). Parental occupational exposure is only marginally associated with CBT (OR = 1.17, 95% CI: 0.99–1.38, I2 = 67.0%). Conclusions: There is an association between CBT and parental pesticides exposure before childbirth, after birth, and residential exposure. It is in line with the IARC Monograph evaluating the carcinogenicity of diazinon, glyphosate, malathion, parathion, and tetrachlorvinphos.

Background: Blood culturing remains the mainstream tool to inform an appropriate treatment in hospital-acquired bloodstream infections and to diagnose any bacteremia. Methods: A retrospective investigation on the prevalence of Gram-negative bacteria (GNB) and their resistance in hospitalized patients by age, sex, and units from blood cultures (BCs) was conducted from January 2018 to April 2020 at Sant’Elia hospital, Caltanissetta, southern Italy. We divided the patient age range into four equal intervals. Results: Multivariate demographic and microbiological variables did not show an association between bacteria distributions and gender and age. The distribution by units showed a higher prevalence of Klebsiella pneumoniae and Acinetobacter baumannii in the intensive care unit (ICU) and Escherichia coli in the non-intensive care units (non-ICUs). The analysis of antibiotic resistance showed that E. coli was susceptible to a large class of antibiotics such as carbapenem and trimethoprim-sulfamethoxazole. K. pneumoniae showed a significant susceptibility to colistin, tigecycline, and trimethoprim-sulfamethoxazole. From the survival analysis, patients with E. coli had a higher survival rate. Conclusions: The authors stress the importance of the implementation of large community-level programs to prevent E. coli bacteremia. K. pneumoniae and E. coli susceptibility patterns to antibiotics, including in the prescription patterns of general practitioners, suggest that the local surveillance and implementation of educational programs remain essential measures to slow down the spread of resistance and, consequently, increase the antibiotic lifespan.

Microsatellite analysis identifies specific genotypes and the genetic relationship between strains. Our objective was to analyze the genotypes of C. parapsilosis strains isolated on different wards of aTertiary- Referral University Center. We evaluated 70 C. parapsilosis strains in total, isolated from samples of patients admitted to five different wards over two years (January 2015-December 2016). Eight microsatellite markers were selected, and two multiplex PCR assays were set up for microsatellite analysis. The 70 strains, examined at eight microsatellite loci, showed 46 different multilocus genotypes profiles. A total of 74 alleles were detected, with an average of 9.25 alleles per locus. The most variable loci were CP6 and CP4, with 20 and 15 alleles, respectively. Four clusters were detected in four out of five wards. A significant cluster that involved 16 patients in the General Surgery department was also found in two patients who had been transferred to the General Medicine ward. Two multiplex PCRs allowed us to minimize costs, define genotypes and study the isolates’ genetic diversity with extreme accuracy, demonstrating the high discriminative power of the microsatellite markers. Molecular epidemiology constitutes an appropriate tool for evaluating horizontal transmission of C. parapsilosis in different clinical settings. Microsatellite genotyping and the utilization of Bruvo’s genetic distance are suitable for detecting and appraising nosocomial fungal infections.

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: 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.

Viral immune evasion by sequence variation is a significant barrier to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine design and coronavirus disease-2019 diffusion under lockdown are unpredictable with subsequent waves. Our group has developed a computational model rooted in physics to address this challenge, aiming to predict the fitness landscape of SARS-CoV-2 diffusion using a variant of the bidimensional Ising model (2DIMV) connected seasonally. The 2DIMV works in a closed system composed of limited interaction subjects and conditioned by only temperature changes. Markov chain Monte Carlo method shows that an increase in temperature implicates reduced virus diffusion and increased mobility, leading to increased virus diffusion.

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.

MicroRNAs (miRNAs) are small single-stranded, non-coding RNA molecules involved in the pathogenesis and progression of cancer, including osteosarcoma. We aimed to clarify the pathways involving miRNAs using new bioinformatics tools. We applied WikiPathways and PathVisio, two open-source platforms, to analyze miRNAs in osteosarcoma using miRTar and ONCO.IO as integration tools. We found 1298 records of osteosarcoma papers associated with the word "miRNA". In osteosarcoma patients with good response to chemotherapy, miR-92a, miR- 99b, miR-193a-5p, and miR-422a expression is increased, while miR-132 is decreased. All identified miRNAs seem to be centered on the TP53 network. This is the first application of PathVisio to determine miRNA pathways in osteosarcoma. MiRNAs have the potential to become a useful diagnostic and prognostic tool in the management of osteosarcoma. PathVisio is a full pathway editor with the potentiality to illustrate the biological events, augment graphical elements, and elucidate all the physical structures and interactions with standard external database identifiers.

Objectives: Agnathia-otocephaly complex is a rare condition characterized by mandibular hypoplasia or agnathia, ear anomalies (melotia/synotia) and microstomia with aglossia. This severe anomaly of the first branchial arch is most often lethal. The estimated incidence is less than 1 in 70.000 births, with etiologies linked to both genetic and teratogenic factors. Most of the cases are sporadic. To date, two genes have been described in humans to be involved in this condition: OTX2 and PRRX1. Nevertheless, the overall proportion of mutated cases is unknown and a significant number of patients remain without molecular diagnosis. Thus, the involvement of other genes than OTX2 and PRRX1 in the agnathia-otocephaly complex is not unlikely. Heterozygous mutations in Cnbp in mice are responsible for mandibular and eye defects mimicking the agnathia-otocephaly complex in humans and appear as a good candidate. Therefore, in this study, we aimed (i) to collect patients presenting with agnathia-otocephaly complex for screening CNBP, in parallel with OTX2 and PRRX1, to check its possible implication in the human phenotype and (ii) to compare our results with the literature data to estimate the proportion of mutated cases after genetic testing. Materials and methods: In this work, we describe 10 patients suffering from the agnathia-otocephaly complex. All of them benefited from array-CGH and Sanger sequencing of OTX2, PRRX1 and CNBP. A complete review of the literature was made using the Pubmed database to collect all the patients described with a phenotype of agnathia-otocephaly complex during the 20 last years (1998-2019) in order (i) to study etiology (genetic causes, iatrogenic causes...) and (ii), when genetic testing was performed, to study which genes were tested and by which type of technologies. Results: In our 10 patients’ cohort, no point mutation in the three tested genes was detected by Sanger sequencing, while array-CGH has allowed identifying a 107-kb deletion encompassing OTX2 responsible for the agnathia-otocephaly complex phenotype in 1 of them. In 4 of the 70 cases described in the literature, a toxic cause was identified and 22 out the 66 remaining cases benefited from genetic testing. Among those 22 patients, 6 were carrying mutation or deletion in the OTX2 gene and 4 in the PRRX1 gene. Thus, when compiling results from our cohort and the literature, a total of 32 patients benefited from genetic testing, with only 34% (11/32) of patients having a mutation in one of the two known genes, OTX2 or PRRX1. Conclusions: From our work and the literature review, only mutations in OTX2 and PRRX1 have been found to date in patients, explaining around one third of the etiologies after genetic testing. Thus, agnathia-otocephaly complex remains unexplained in the majority of the patients, which indicates that other factors might be involved. Although involved in first branchial arch defects, no mutation in the CNBP gene was found in this study. This suggests that mutations in CNBP might not be involved in such phenotype in humans or that, unlike in mice, a compensatory effect might exist in humans. Nevertheless, given that agnathia-otocephaly complex is a rare phenotype, more patients have to be screened for CNBP mutations before we definitively conclude about its potential implication. Therefore, this work presents the current state of knowledge on agnathia-otocephaly complex and underlines the need to expand further the understanding of the genetic bases of this disorder, which remains largely unknown. Clinical relevance: We made here an update and focus on the clinical and genetic aspects of agnathia-otocephaly complex as well as a more general review of craniofacial development.

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.

This paper discusses the use of advanced mathematical tools in nursing research, such as mathematical models used in medicine for description and prediction of experimental tumor growth. They are rarely used in nursing research, but fortunately in the last decade, their use is increased, mainly due to artificial intelligence and Big Data, with great benefits for further nursing development. Therefore, a strong interaction between nurses and mathematicians is needed to improve nursing research, and consequently, the nurses’ performance in daily work. Significance for public health The study described in this paper is significant for public health, because it discusses the importance of using mathematical models in nursing research. Mathematical models used in many scientific areas could impact nurses' daily work, guiding their decisions and helping them choose better strategies, resulting in an improvement in their performance.

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.

The progression of cardiovascular research is often impeded by the lack of reliable disease models that fully recapitulate the pathogenesis in humans. These limitations apply to both in vitro models such as cell-based cultures and in vivo animal models which invariably are limited to simulate the complexity of cardiovascular disease in humans. Implementing human heart tissue in cardiovascular research complements our research strategy using preclinical models. We established the Human Explanted Heart Program (HELP) which integrates clinical, tissue and molecular phenotyping thereby providing a comprehensive evaluation into human heart disease. Our collection and storage of biospecimens allow them to retain key pathogenic findings while providing novel insights into human heart failure. The use of human non-failing control explanted hearts provides a valuable comparison group for the diseased explanted hearts. Using HELP we have been able to create a tissue repository which have been used for genetic, molecular, cellular, and histological studies. This review describes the process of collection and use of explanted human heart specimens encompassing a spectrum of pediatric and adult heart diseases, while highlighting the role of these invaluable specimens in translational research. Furthermore, we highlight the efficient procurement and bio-preservation approaches ensuring analytical quality of heart specimens acquired in the context of heart donation and transplantation., Graphical abstract Illustration of the Human Explanted Heart Program (HELP) pathway as an integrative program that brings together clinicians and researchers aiming to unravel the underpinnings of cardiovascular disease and discover novel therapeutics. Our biobank contains tissue collections covering all sections of the explanted heart. A comprehensive review of the research participant clinical profile is also integrated into the analysis while complementary academic partnerships enabled us to broaden and diversify our approach to human heart disease.Unlabelled Image, Highlights • HELP - the largest research-integrated human heart transplant platform in Canada • Sizable specimen inventory of HELP enables research on a spectrum of heart diseases. • Systematic review of the methodology for HELP biobank management • Detailed evaluation on use of human hearts in translational cardiovascular medicine

Background: Ex situ heart perfusion (ESHP) preserves the donated heart in a perfused, beating condition preventing cold storage–related ischemia and provides a platform to evaluate myocardial viability during preservation. However, myocardial function declines gradually during ESHP. Extracorporeal circulation systems are associated with the induction of systemic inflammatory and stress responses. Our aim was to evaluate the incidence of inflammation and induction of endoplasmic reticulum stress responses during an extended period of ESHP. Methods: Cardiac function, myocardial tissue injury, markers of inflammation, oxidative stress, and endoplasmic reticulum stress were assessed in healthy pig hearts, perfused for 12 hours either in nonworking mode (non-WM=7) or working mode (WM, n=6). Results: Cardiac function declined during ESHP but was significantly better preserved in the hearts perfused in WM (median 11-hour cardiac index/1-hour cardiac index: WM=27% versus non-WM=9.5%, P =0.022). Myocardial markers of endoplasmic reticulum stress were expressed higher in ESHP hearts compared with in vivo samples. The proinflammatory cytokines and oxidized low-density lipoprotein significantly increased in the perfusate throughout the perfusion in both perfusion groups. The left ventricular expression of the cytokines and malondialdehyde was induced in non-WM, whereas it was not different between WM and in vivo. Conclusions: Myocardial function declines during ESHP regardless of perfusion mode. However, ESHP in WM may lead to superior preservation of myocardial function and viability. Both inflammation and endoplasmic reticulum stress responses are significantly induced during ESHP and may contribute to the myocardial functional decline, representing a potential therapeutic target to improve the clinical donor heart preservation.

Since the declaration of the COVID-19 pandemic, a lot of data has invaded our lives, and the conflicting findings have caused us to be frantic about the correct course action. Strict isolation and social distancing measures can flatten the coronavirus infectious curve, and the use of facemask needs to be encouraged and facilitated in crowded places, particularly in hospitals where the 6-feet social distancing cannot be adopted because of physical barriers.

Background Germline pathogenic variants impairing the caspase recruitment domain family member 11 (CARD11)–B cell chronic lymphocytic leukemia/lymphoma 10 (BCL10)–MALT1 paracaspase (MALT1) (CBM) complex are associated with diverse human diseases including combined immunodeficiency (CID), atopy, and lymphoproliferation. However, the impact of CARD11 deficiency on human B-cell development, signaling, and function is incompletely understood. Objectives This study sought to determine the cellular, immunological, and biochemical basis of disease for 2 unrelated patients who presented with profound CID associated with viral and fungal respiratory infections, interstitial lung disease, and severe colitis. Methods Patients underwent next-generation sequencing, immunophenotyping by flow cytometry, signaling assays by immunoblot, and transcriptome profiling by RNA-sequencing. Results Both patients carried identical novel pathogenic biallelic loss-of-function variants in CARD11 (c.2509C>T; p.Arg837∗) leading to undetectable protein expression. This variant prevented CBM complex formation, severely impairing the activation of nuclear factor-κB, c-Jun N-terminal kinase, and MALT1 paracaspase activity in B and T cells. This functional defect resulted in a developmental block in B cells at the naive and type 1 transitional B-cell stage and impaired circulating T follicular helper cell (cTFH) development, which was associated with impaired antibody responses and absent germinal center structures on lymph node histology. Transcriptomics indicated that CARD11-dependent signaling is essential for immune signaling pathways involved in the development of these cells. Both patients underwent hematopoietic stem cell transplantations, which led to functional normalization. Conclusions Complete human CARD11 deficiency causes profound CID by impairing naive/type 1 B-cell and cTFH cell development and abolishing activation of MALT1 paracaspase, NF-κB, and JNK activity. Hematopoietic stem cell transplantation functionally restores impaired signaling pathways.

The remodeling of interlobular bile ducts is a fascinating interplay in the perinatal liver. There are excretory structures that need to be built to drain bile from the hepatocytes. These structures are vital for the wellbeing of the organism and are built during the ontogenesis of the liver, which plays a major role in life. The bile flows from the bile canaliculus of two adjacent hepatocytes through the Hering’s canals into the interlobular bile ducts, which are in the portal triads between the hepatic lobules. The interlobular bile ducts will transfer the bile to segmental bile ducts and major bile ducts, which converge into the right and left major bile ducts. Finally, the bile reaches the common bile duct and ductus choledochus following joining with the cystic duct of the gallbladder. The ductus choledochus discharges at the duodenal papilla. The proper remodeling of the primitive (embryonic) ductal plate of the liver is at the basis of the formation of the interlobular bile ducts, which are positioned about three diameters from the portal artery and lined by healthy cholangiocytes. A paucity of the interlobular bile ducts (PIBD) is defined as an interlobular bile duct to portal tract (IBD/PT) ratio of 0.5 or less in a needle liver biopsy. In this chapter, the paucity of interlobular bile ducts is reviewed into three paragraphs, including the cholangiocyte structure, the ductal plate remodeling of the liver, and the clinical and genetic syndromes associated with the lack or scarcity of the IBDs.

The urinary tract obstruction is a common problem in pediatrics. When a defect in the urinary tract blocks the normal flow of urine, the urine backs up and causes hydroureters and hydronephrosis. Such abnormalities of the urinary tract may be identified before or after the baby is born. In this chapter some anomalies of the urinary tract as well the pathology of the male genital system are discussed.

The peripheral nervous system is that part of the nervous system outside the brain and spinal cord. The peripheral nervous system is often described with the muscle, and indeed neuropathologists deliver diagnosis on both nerve and muscle pathology other than on pathology of the central nervous system. The peripheral nervous system includes the cranial nerves and spinal nerves. In this chapter, we will present on the development of the epimeric and hypomeric muscle, myogenic and neurogenic myopathies, as well as the non-neoplastic and neoplastic of the peripheral nervous system. Motor neuron dysfunction results in hypotonia or paralysis. Sensory neuron dysfunction results in abnormal or lost sensation. Some of the disorders, particularly the mitochondrial myopathies, are often progressive and fatal. Illustrative materials for schwannoma, neurofibroma, and malignant peripheral nerve sheath tumor are provided.

Osteogenic sarcoma is probably one of the terrifying diagnoses in pediatrics. Although the knowledge of the etiopathogenesis of this neoplastic disease has increased in the last few decades, we are still experiencing no progress for patients that do not respond adequately to the chemotherapy protocols. The quest for the full understanding of the etiopathogenesis of this disease is one of the central preoccupations of pediatric oncologists. In this chapter, the current knowledge of this neoplasm, the differential diagnosis with other bony tumors, and perspective are highlighted. The contribution of the insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 (IGFBP-3) is also mentioned. Moreover, illustrations of sporadic bone diseases in adolescence and youth are presented, including chondromyxoid fibroma, giant cell tumor, and plasmacytoma. The non-neoplastic illness is explained with illustrative cases mainly pointing to the osteomyelitis but also to the avascular necrosis as a result of numerous studies on experimental models of avascular necrosis.

The upper urinary system also plays a significant role in pediatric pathology for both cystic and non-cystic renal disease. The cystic renal disease has a considerable relevance not only for the child but also for future generations. Some cystic renal diseases have been clarified in the last decade and also associated with some extrarenal defects. The renal biopsy is also a critical task in a Children’s Hospital, mainly if the healthcare institution also covers renal transplantation.

Purpose of Review: The impacts of climate change on biodiversity in the last three decades have increasingly assumed from significant to threatening proportions and this causes major global concerns. This study aims at examining the recent and future impacts of global climate change on both ecological resources and human well-being. This review study is based on the general concept of ecological resilience: that coping with climate change stresses and disturbances depends on social resilience, political and environmental strategies accessible in a community. The study assessed over 300 peer-reviewed publications, both articles and books, which linked climate change impacts on ecosystems to social/health resilience of people in the specific regions. Publications on that were focused on general impacts of climate change on global ecology, ecosystem distribution shifts and phenology change; the ecological and social/health resilience, in the tropic and polar regions, were reviewed. Recent Findings: The major finding of this study is that there is considerable variation in magnitudes and patterns of responses to climate change in different regions, even with an overall review of scientific studies on the global ecosystem and human health. Despite this, what is obvious is that change in the ecosystem in Polar Regions will continue to have significant impacts on the global environment, flora, fauna and ultimately human well-being. Summary: There are many uncertainties, though, on the possible effects of climate change ecosystem and soils and their severe biological, social, cultural and economic consequences. Notwithstanding these uncertainties, the impacts of climate change on both ecosystem and human socio-cultural activities are very likely to become even more widespread in the near future.

The excretory biliary tract is one of the primary platforms of investigation for neonatal and infantile cholestasis. Some diseases linked to the gallbladder and extrahepatic biliary system of the childhood and youth are presented.

This study aims at assessing the impacts of climate indices on the spatiotemporal distribution of malaria and meningitis in Nigeria. The primary focus of the research is to develop an Early Warning System (EWS) for assessing climate variability implications on malaria and meningitis spread in the study area. Both climate and health data were used in the study to determine the relationship between climate variability and the occurrence of malaria and meningitis. The assessment was based on variations in different ecological zones in Nigeria. Two specific sample locations were randomly selected in each ecological zone for the analysis. The climatic data used in this study are dekadal precipitation, minimum and maximum temperature between 2000 and 2018, monthly aerosol optical depth between 2000 and 2018. The results show that temperature is relatively high throughout the year because the country is located in a tropical region. The significant findings of this study are that rainfall has much influence on the occurrence of malaria, while temperature and aerosol have more impact on meningitis. We found the degree of relationship between precipitation and malaria, there is a correlation coefficient R2 ≥ 70.0 in Rainforest, Freshwater, and Mangrove ecological zones. The relationship between temperature and meningitis is accompanied by R2 ≥ 72.0 in both Sahel and Sudan, while aerosol and meningitis harbour R2 = 77.33 in the Sahel. The assessment of this initial data seems to support the finding that the occurrences of meningitis are higher in the northern region, especially the Sahel and Sudan. In contrast, malaria occurrence is higher in the southern part of the study area. In all, the multiple linear regression results revealed that rainfall was directly associated with malaria with β = 0.64, p = 0.001 but aerosol was directly associated with meningitis with β = 0.59, p

The liver, as one of the most central glands of the body, is the most driving force in the development of the embryo and fetus. The study of the primitive biliary system is crucial for the detection and correct management of numerous cholestasis syndromes of neonatal age and infancy. The explanation of the slowdown period of bile duct morphogenesis between 22 and 32 weeks gestation as well as ductal plate malformation will be an integral part of this chapter. The clarification of the neonatal iron storage disorder as gestational alloimmune liver disease and the identification of numerous molecular mechanisms for familiar intrahepatic cholestasis have been the pillars in the last decade to address the management of these infants. The presentation of several cholestatic liver diseases as well as metabolic disorders is in this chapter and will be accompanied by the introduction of benign, malignant tumors that may target the liver in childhood and youth.

The respiratory system is crucial in the life of some overlapping specialties in medicine. In utero, the lung faces a change of the structure which is rarely seen in any other systems. The very myxoid tissue- and glycogen-rich pseudoglandular phase does not become mature that only in the late infancy and early childhood. Respiratory disease in the newborn is a well-known complication of prematurity, but in the last decade, a large number of entities have been added to the chILD or Children’s Interstitial Lung Disease adding complexity to the adult interstitial lung disease. In fact, youth may develop both pediatric and adult interstitial lung diseases, and pediatricians and pathologists should be aware of the pitfalls in not addressing an adult interstitial lung disease correctly in an adolescent. Some congenital anomalies of the abnormal driven foregut budding of the lung development may also be considered as an essential topic in studying pediatrics and adolescence. This chapter is completed with more than 400 photographs illustrating several lines of abnormal processes that may be present in a developing lung. Similar to non-neoplastic disease, both adult and specific pediatric neoplastic lung diseases need to get attention to avoid the possibility of pitfalls. In the last decade, some case reports of pulmonary carcinoma and malignant mesothelioma of the pleura have been reported in children adding complexity in carcinogenesis of this very complex organ. The molecular genetics has helped to clarify several carcinogenetic pathways not anymore limited to DICER1 gene mutations identified in pleuropulmonary blastoma.

The neuropathology is the study of disease of nervous system tissue working closely with the clinical disciplines of neurology, neurosurgery, and metabolic experts. This chapter is far from being a comprehensive study of the brain and spinal cord but will allow dealing with the most common pediatric neuropathology topics, such as the holoprosencephaly and aprosencephaly. A session will be devoted to the neuropathology of the acardius or twin reversed arterial perfusion sequence.

General and pediatric pathologists should have enough knowledge of the diagnosis and treatment of head and neck lesions in children and youth to liaise appropriately with practitioners, pediatricians, and oncologists and provide appropriate medical care for them. Delay in providing adequate care can sometimes lead to prolonged and unnecessary morbidity, even in the case of benign tumors with a favorable prognosis. Malignant tumors of head and neck in children may be associated with high rates of morbidity and mortality and are considered the second most important etiologic factor for death after the second infancy through adolescence. In this chapter, the non-neoplastic and neoplastic pathology of head and neck in childhood and youth is taken under the lens.

Gynecologic pathology has shown a lot of new achievements in the last decade with progress in light microscopy, immunohistochemistry, and molecular diagnostics. In this chapter, the pathology of the female genital system of childhood and youth is discussed in detail. Plenty of illustrative material accompanies the discussion of several gynecologic topics. There will be a presentation of sporadic malignant tumors, including uterine neuroblastoma, an endometrioid endometrial carcinoma, and extramammary Paget disease. Some cervical adenocarcinomas only are related to high-risk human papillomavirus (HPV) infection, while squamous cell carcinoma of the cervix is virtually HPV-related. The precise pathogenesis, molecular features, and pathomorphological findings of neoplastic disease are illustrated. The non-neoplastic disease will focus on disorders linked to maldevelopment.

The pathology of the placenta and the conception has interested scientists and physicians for centuries. In this chapter, the pathology of the placenta is illustrated according to pathophysiology emphasizing the role of implantation, formation, maturation, and vascularization of the placenta in the early pregnancy. The pathology of the late pregnancy is grouped according to the timing of the events that can be considered catastrophic for a pregnancy. Thus, acute diseases are placental abruption, fetal bleeding, and injury or damages to the integrity of the umbilical cord (“ABC”). In the late pregnancy, subacute diseases include amniotic fluid infection, meconium staining of the membranes, fetomaternal hemorrhages, and the appearance of nucleated erythrocytes as the status of prolonged hypoxia. Chronic conditions include vasculopathies that render the intervillous space unpracticable for the exchange between mother and fetus. Preneoplastic and neoplastic lesions may complicate a pregnancy and trouble the postpartum period in case of follow-up and chemotherapy are required. A number of nonscientific literature have accompanied the description of several congenital disabilities, and historiography found how much progress and evolution was present in the Byzantine society long before the brothers Chang and Eng Bunker were known as Siamese twins. The description of the surgical separation performed by Byzantine surgeons is adamantine as described by Leon Grammatikos and Theodoros Daphnopates, two major Byzantine authorities, in Constantinople during the second half of the tenth century. In this chapter, the congenital disabilities are grouped according to the etiopathogenesis during missteps of embryology. Finally, infection in pregnancy and fetal growth restriction are reviewed according to the eyes of the fetal medicine, and a step-by-step approach to the handling and examination of the placenta is provided.

In the 21st century, the determination of alert thresholds remains the most challenging and controversial issue in clinical pediatrics. Pre-analytical, analytical, and post-analytical matters will consolidate or undermine the fate of any laboratory process. Pre-analytical issues need to be cleared off before the laboratory physician can dispatch the result to the pediatrician in charge. Once it is cleared off, the classification of essential laboratory results is paramount. It is more than an academic exercise and may be subdivided in the order of priority we handle it to inform promptly and safely the primary physicians. Currently, we are applying new modes of making sure relevant information is transmitted without interrupting the standard workflow of the primary physicians in charge for the child, who eventually need a fast line of action for results that may be life-threatening.