CHAMP1-Related Disorder: Sharing 20 Years of thorough Clinical Follow-Up and Review of the Literature.

Intellectual disability (ID) is a prevalent neurodevelopmental disorder characterized by limitations in intellectual functioning and adaptive behavior. While the causes of ID are still largely unknown, it is believed to result from a combination of environmental exposures and genetic abnormalities. Recent advancements in genomic studies and clinical genetic testing have identified numerous genes associated with neurodevelopmental disorders (NDDs), including ID. One such gene is CHAMP1, which plays a role in chromosome alignment and has been linked to a specific type of NDD called CHAMP1 disease. This report presents the case of a 21-year-old Lebanese female patient with a de novo mutation in CHAMP1. In addition to ID and NDD, the patient exhibited various clinical features such as impaired language, dysmorphic features, macrocephaly, thoracic hyperkyphosis, decreased pain sensation, and metabolic syndrome. These findings expand the understanding of the clinical spectrum associated with CHAMP1 mutations and highlight the importance of comprehensive follow-up for improved prognosis. Overall, this case contributes to the knowledge of CHAMP1-related NDDs by describing additional clinical features associated with a CHAMP1 mutation. The findings underscore the need for accurate diagnosis, thorough follow-up, and personalized care for individuals with CHAMP1 mutations to optimize their prognosis.

Chemical pancreatectomy in non-human primates ablates the acini and ducts and enhances beta-cell function.

Chronic pancreatitis is a debilitating disease affecting millions worldwide. These patients suffer from bouts of severe pain that are minimally relieved by pain medications and may necessitate major surgeries with high morbidity and mortality. Previously, we demonstrated that "chemical pancreatectomy," a pancreatic intraductal infusion of dilute acetic acid solution, ablated the exocrine pancreas while preserving the endocrine pancreas. Notably, chemical pancreatectomy resolved chronic inflammation, alleviated allodynia in the cerulein pancreatitis model, and improved glucose homeostasis. Herein, we extensively tested the feasibility of a chemical pancreatectomy in NHPs and validated our previously published pilot study. We did serial computed tomography (CT) scans of the abdomen and pelvis, analyzed dorsal root ganglia, measured serum enzymes, and performed histological and ultrastructural assessments and pancreatic endocrine function assays. Based on serial CT scans, chemical pancreatectomy led to the loss of pancreatic volume. Immunohistochemistry and transmission electron microscopy demonstrated exocrine pancreatic ablation with endocrine islet preservation. Importantly, chemical pancreatectomy did not increase pro-nociceptive markers in harvested dorsal root ganglia. Also, chemical pancreatectomy improved insulin secretion to supranormal levels in vivo and in vitro. Thus, this study may provide a foundation for translating this procedure to patients with chronic pancreatitis or other conditions requiring a pancreatectomy.

Chemical pancreatectomy in non-human primates ablates the acini and ducts and enhances beta-cell function.

Chronic pancreatitis is a debilitating disease affecting millions worldwide. These patients suffer from bouts of severe pain that are minimally relieved by pain medications and may necessitate major surgeries with high morbidity and mortality. Previously, we demonstrated that "chemical pancreatectomy," a pancreatic intraductal infusion of dilute acetic acid solution, ablated the exocrine pancreas while preserving the endocrine pancreas. Notably, chemical pancreatectomy resolved chronic inflammation, alleviated allodynia in the cerulein pancreatitis model, and improved glucose homeostasis. Herein, we extensively tested the feasibility of a chemical pancreatectomy in NHPs and validated our previously published pilot study. We did serial computed tomography (CT) scans of the abdomen and pelvis, analyzed dorsal root ganglia, measured serum enzymes, and performed histological and ultrastructural assessments and pancreatic endocrine function assays.  Based on serial CT scans, chemical pancreatectomy led to the loss of pancreatic volume. Immunohistochemistry and transmission electron microscopy demonstrated exocrine pancreatic ablation with endocrine islet preservation. Importantly, chemical pancreatectomy did not increase pro-nociceptive markers in harvested dorsal root ganglia. Also, chemical pancreatectomy improved insulin secretion to supranormal levels in vivo and in vitro. Thus, this study may provide a foundation for translating this procedure to patients with chronic pancreatitis or other conditions requiring a pancreatectomy.

Respiratory Adverse Events After LMA® Mask Removal in Children: A Randomized Trial Comparing Propofol to Sevoflurane.

BACKGROUND: The removal of the laryngeal mask airway (LMA®) in children may be associated with respiratory adverse events. The rate of occurrence of these adverse events may be influenced by the type of anesthesia. Studies comparing total intravenous anesthesia (TIVA) with propofol and sevoflurane are limited with conflicting data whether propofol is associated with a lower incidence of respiratory events upon removal of LMA as compared to induction and maintenance with sevoflurane. We hypothesized that TIVA with propofol is superior to sevoflurane in providing optimal conditions and improved patient's safety during emergence. METHODS: In this prospective, randomized, double-blind clinical trial, children aged 6 months to 7 years old were enrolled in 1 of 2 groups: the TIVA group and the sevoflurane group. In both groups, patients were mechanically ventilated. At the end of the procedure, LMAs were removed when patients were physiologically and neurologically recovered to a degree to permit a safe, natural airway. The primary aim of this study was to compare the occurrence of at least 1 respiratory adverse event, the prevalence of individual respiratory adverse events, and the airway hyperreactivity score following emergence from anesthesia between the 2 groups. Secondary outcomes included ease of LMA insertion, quality of anesthesia during the maintenance phase, hemodynamic stability, time to LMA removal, and incidence of emergence agitation. RESULTS: Children receiving TIVA with propofol had a significantly lower incidence (10.8.% vs 36.2%; relative risk, 0.29; 95% CI [0.14-0.64]; P = .001) and lower severity ( P = .01) of respiratory adverse outcomes compared to the patients receiving inhalational anesthesia with sevoflurane. There were no statistically significant differences in secondary outcomes between the 2 groups, except for emergence agitation that occurred more frequently in patients receiving sevoflurane ( P < .001). CONCLUSIONS: Propofol induction and maintenance exerted a protective effect on healthy children with minimal risk factors for developing perioperative respiratory complications, as compared to sevoflurane.

Female awareness about the preconception use of folic acid supplements in childbearing age: A cross-sectional study.

AIMS: Folic acid is required for the growth and development of the fetus. There is strong evidence that taking folic acid before pregnancy and during the first trimester reduces the risk of neural tube defects (NTDs). This study aimed to assess women's awareness of preconception folic acid supplementation and its importance to the mother and the fetus. METHODS: This was a cross-sectional questionnaire study conducted in Saudi Arabia between January and April 2019. An electronic questionnaire tool was designed and distributed using Google Forms through social media (Facebook and WhatsApp) websites. Binary logistics regression was used to estimate odds ratios (ORs), with 95% confidence intervals (CIs) for predictors of poor levels of awareness about folic acid. RESULTS: A total of 514 women participated in this study. The age range for the study participants was 18-45 years. Only 24.1% of the participants reported that they routinely took folic acid. The most commonly reported source of information about folic acid use was the doctor. The majority of the participants had poor awareness of folic acid use. Older age (30 years and above) and not taking regular folic acid supplements were important predictors of poor awareness of folic acid. Having a university degree or higher education was an important predictor of increased awareness about folic acid. CONCLUSION: Our study found that the awareness of the Saudi women was poor in identifying the generic name of folic acid, recognising the sources of folic acid, the correct dose of folic acid, and the side effects of high doses of folic acid and that there was good knowledge about the importance of folic acid, the consequences of folic acid deficiency, and the belief that even non-pregnant women and girls of childbearing age should take folic acid.

Epidemiology and clinical characteristics of viral infections in hospitalized children and adolescents with cancer in Lebanon.

BACKGROUND: Viral infections in children and adolescents with malignancy are commonly encountered and have a significant impact on morbidity and mortality. Studies and epidemiological data regarding viral infections in children with cancer in developing countries are lacking. This retrospective cohort study aims to assess the burden of viral infections in children and adolescents with cancer, by assessing prevalence, risk factors, as well as morbidity and mortality of common viruses over a period of 8 years. METHODS AND FINDINGS: Medical records of cancer patients treated at the Children Cancer Center of Lebanon were reviewed and 155 participants under the age of 21 were identified with at least one documented viral infection during the period from July 2009 to November 2017. This subset included 136 participants with active malignancy and 19 participants with a history of cancer who underwent hematopoietic stem cell transplantation [HSCT] and were in remission; the latter group was analyzed separately. Information regarding participant characteristics, hospital course, and complications were obtained. Associations between viral infections and certain factors were assessed. In the cohort, 64% were male, 81% were Lebanese. In participants with active malignancy, 90% received chemotherapy in the 6 months preceding the viral infection episode, 11% received radiotherapy. 51% of participants were neutropenic at the time of viral detection, and 77% were lymphopenic. 17% experienced a bacterial co-infection, and 3 experienced a viral co-infection. Among 162 viral infection episodes, clinically diagnosed skin infections, mainly herpes simplex virus type 1 and varicella-zoster virus, were the most common [44% of cases]. These were followed by laboratory-proven systemic herpes infections: cytomegalovirus [14%] and Epstein-Barr virus [6%]. Respiratory viruses: influenza and respiratory syncytial virus, accounted for 9% and 4%, respectively, whereas rotavirus represented 11% and BK virus represented 3% of cases. Acute lymphocytic leukemia was the most prevalent neoplasia [57%]. Fever was the most common presenting symptom [55%] and febrile neutropenia was the reason for admission in 24% of cases. The mean length of stay was significantly longer in participants with cytomegalovirus infections and significantly lower in rotavirus infection. Admission to the ICU occurred in 9%, complications in 8%, and mortality in 5%. Participants with viral infections post-HSCT were noted to have a significantly longer length of hospital stay compared to non-HSCT participants, with no other significant differences in clinical course and outcome. The study was limited by its retrospective nature and by the late introduction and underuse of multiplex PCR panels, which may have led to underdiagnosis of viral infections. CONCLUSIONS: Viral infections were prevalent in our sample of cancer patients and may have contributed to morbidity and mortality. Newly available viral diagnostics are likely to vastly increase the number and scope of detectable viral infections in this population. Prospective studies using multiplex PCR technology with systematic testing of patients will be more helpful in defining the burden of viral infections. Furthermore, efforts at antimicrobial stewardship would benefit from the identification of viral causes of infection and limit the unnecessary use of antibiotics in the pediatric cancer population.

Andrographolide potentiates the antitumor effect of topotecan in acute myeloid leukemia cells through an intrinsic apoptotic pathway.

BACKGROUND: Topotecan (TP) is an anticancer drug acting as topoisomerase I inhibitor that is used in the treatment of many types of cancers including leukemia, but it has significant side effects. Andrographolide, a compound extracted from Andrographis paniculata, was recently proven to inhibit the growth of cancer cells and can induce apoptosis. The aim of this study is to investigate the possible synergism between TP and andrographolide in acute myeloid cells in vitro. MATERIALS AND METHODS: U937 acute myeloid leukemic cells were cultured using Roswell Park Memorial Institute (RPMI) medium and then treated for 24 h with TP and andrographolide prepared through the dilution of dimethyl sulfoxide (DMSO) stocks with RPMI on the day of treatment. Cell proliferation was assessed using cell proliferation assay upon treatment with both compounds separately and in combination. Cell-cycle study and apoptosis detection were performed by staining the cells with propidium iodide (PI) stain and Annexin V/PI stain, respectively, followed by flow cytometry analysis. Western blotting was used to assess the expression of various proteins involved in apoptotic pathways. RESULTS: Both TP and andrographolide showed an antiproliferative effect in a dose-dependent manner when applied on U937 cells separately; however, pretreating the cells with andrographolide before applying TP exhibited a synergistic effect with lower inhibitory concentrations (half-maximal inhibitory concentration). Treating the cells with TP alone led to specific cell-cycle arrest at S phase that was more prominent upon pretreatment combination with andrographolide. Using Annexin V/PI staining to assess the proapoptotic effect following the pretreatment combination showed an increase in the number of apoptotic cells, which was supported by the Western blot results that manifested an upregulation of several proapoptotic proteins expression. CONCLUSION: The pretreatment of U937 with andrographolide followed by low doses of TP showed an enhancement in inducing apoptosis when compared to the application of each compound separately.