Revolutionizing cancer therapy: nanoformulation of miRNA-34 - enhancing delivery and efficacy for various cancer immunotherapies: a review.

Despite recent advancements in cancer therapies, challenges such as severe toxic effects, non-selective targeting, resistance to chemotherapy and radiotherapy, and recurrence of metastatic tumors persist. Consequently, there has been considerable effort to explore innovative anticancer compounds, particularly in immunotherapy, which offer the potential for enhanced biosafety and efficacy in cancer prevention and treatment. One such avenue of exploration involves the miRNA-34 (miR-34) family, known for its ability to inhibit tumorigenesis across various cancers. Dysregulation of miR-34 has been observed in several human cancers, and it is recognized as a tumor suppressor microRNA due to its synergistic interaction with the well-established tumor suppressor p53. However, challenges have arisen with the therapeutic application of miR-34a. These include its susceptibility to degradation by RNase in serum, limiting its ability to penetrate capillary endothelium and reach target cells, as well as reports of immunoreactive adverse reactions. Furthermore, unexpected side effects may occur, such as the accumulation of therapeutic miRNAs in healthy tissues due to interactions with serum proteins on nano-vector surfaces, nanoparticle breakdown in the bloodstream due to shearing stress, and unsuccessful extravasation of nanocarriers to target cells owing to interstitial fluid pressure. Despite these challenges, miR-34a remains a promising candidate for cancer therapy, and other members of the miR-34 family have also shown potential in inhibiting tumor cell proliferation. While the in vivo applications of miR-34b/c are limited, they warrant further exploration for oncotherapy. Recently, procedures utilizing nanoparticles have been developed to address the challenges associated with the clinical use of miR-34, demonstrating efficacy both in vitro and in vivo. This review highlights emerging trends in nanodelivery systems for miR-34 targeting cancer cells, offering insights into novel nanoformulations designed to enhance the anticancer therapeutic activity and targeting precision of miR-34. As far as current knowledge extends, no similar recent review comprehensively addresses the diverse nanoformulations aimed at optimizing the therapeutic potential of miR-34 in anticancer strategies.

Burnout and resilience among physical therapy students: a cross-sectional study.

BACKGROUND: This study aimed to examine the prevalence of burnout, determine burnout-related factors, investigate resilience levels, and assess the relationship between burnout and resilience among physical therapy (PT) students at King Saud University (KSU) in Saudi Arabia. MATERIAL AND METHODS: This cross-sectional study involved 153 PT students studying at KSU between January and March 2023. The participants completed an online questionnaire, a Maslach Burnout Inventory, and a Brief Resilience Scale. RESULTS: Low-to-moderate levels of Emotional Exhaustion (EE) were observed in 85% of the participants and high Depersonalization (DP) levels were reported by 34.2%. Female participants reported higher levels of EE and DP, whereas males had a greater prevalence of low Personal Achievement (PA) levels. Approximately 6.5% of the study participants reported high burnout levels (a combination of high DP, high EE, and low PA). Academic stress, followed by sleeping difficulties and changes in the academic year structure, were the most important factors contributing to higher levels of burnout (75.2%, 56.9%, and 43.8%, respectively). Most study participants around (66.0%) reported normal resilience levels. A significant correlation was detected between resilience and 2 domains of burnout (DP and PA), with the correlation being negative and weak for DP and positive and moderate for PA. CONCLUSIONS: Overall, low-to-moderate levels of burnout were observed among the PT students who took part. Related factors that contributed to burnout were academic stress, sleeping difficulties, and academic year structure. A normal level of resilience was found to be significantly related to DP and PA but not to EE on the burnout subscales. Higher levels of resilience can be considered to play a protective role against burnout among PT students. Med Pr Work Health Saf. 2024;75(4):343-354.

Hybrid Organic-Inorganic Copper and Cobalt Complexes for Antimicrobial Potential Applications.

BACKGROUND/AIMS: The naturally occurring phenolic chemical curcumin (CUR), which was derived from the Curcuma longa plant, has a variety of biological actions, including anti-inflammatory, antimicrobial, antioxidant, and anticancer activities. Curcumin is known for its restricted bioavailability due to its hydrophobicity, poor intestinal absorption, and quick metabolism. To boost the biological effects of these bioactive molecules, it is necessary to raise both their bioavailability and their solubility in water. Aim: The aim of this study is to synthesize and characterize hybrid organic-inorganic complexes of copper and cobalt, and to evaluate their antimicrobial potential against a range of pathogenic microorganisms. METHODS: The synthesis of metal curcumin complexes (Cu-CUR and Co-CUR) was achieved by mixing curcumin with copper acetate monohydrate. The solid residue was isolated, filtered, and dried in an oven. X-ray diffraction analysis was used to identify the structure and phase of the prepared samples. FTIR spectra were recorded using a Shimadzu 2200 module. The antimicrobial activity of the prepared complexes was evaluated against four bacterial strains and two Candida species. The chemical materials were dissolved in DMSO to a final concentration of 20%, and the plates were incubated at 37°C for 24 hours. The results showed that the prepared complexes had antimicrobial activity against the tested microorganisms. RESULTS: The study compared the Powder X-ray diffraction (XRD) patterns of prepared copper and cobalt complexes to pure curcumin, revealing new, isostructural complexes. The FTIR analysis showed that the Cu-CUR and Co-CUR complexes varied in their inhibitory effect against microorganisms, with Co-CUR being more effective. The results are consistent with previous studies showing the cobalt-curcumin complex was effective against various bacterial genera, with inhibition activity varying depending on the species and strains of microorganisms. CONCLUSION: Copper and cobalt curcumin complexes, synthesized at room temperature, exhibit high crystallinity and antimicrobial activity. Co-CUR, with its superior antibacterial potential, outperforms pure curcumin in inhibiting microbes. Further investigation is needed to understand their interaction mechanisms with bacteria and fungi.

A Comprehensive Insight and In Silico Analysis of CircRNAs in Hepatocellular Carcinoma: A Step toward ncRNA-Based Precision Medicine.

Circular RNAs (circRNAs) are cardinal players in numerous physiological and pathological processes. CircRNAs play dual roles as tumor suppressors and oncogenes in different oncological contexts, including hepatocellular carcinoma (HCC). Their roles significantly impact the disease at all stages, including initiation, development, progression, invasion, and metastasis, in addition to the response to treatment. In this review, we discuss the biogenesis and regulatory functional roles of circRNAs, as well as circRNA-protein-mRNA ternary complex formation, elucidating the intricate pathways tuned by circRNAs to modulate gene expression and cellular processes through a comprehensive literature search, in silico search, and bioinformatics analysis. With a particular focus on the interplay between circRNAs, epigenetics, and HCC pathology, the article sets the stage for further exploration of circRNAs as novel investigational theranostic agents in the dynamic realm of HCC.

Challenges of distance learning encountering nursing students after the COVID-19 pandemic: a study from the Middle East.

BACKGROUND: The COVID-19 pandemic necessitated an abrupt transition to online learning in nursing education, presenting unprecedented challenges. This research aims to comprehensively assess the challenges faced by nursing students during this transition, exploring key issues, recommending strategies, and analyzing their impact on student perceptions. METHODS: Using a cross-sectional design, the study surveyed 941 nursing students across eight Arab countries-Jordan, Iraq, Lebanon, Palestine, Oman, KSA, UAE, and Egypt-to ensure a representative sample and enhance external validity. Data collection involved a thorough survey covering academic, technological, and administrative challenges. Reliability analysis, descriptive statistics, and variance analysis using Kruskal -Wallis and Mann-Whitney tests were conducted to examine differences between countries and sociodemographic variables. RESULTS: Descriptive statistics revealed significant demographic disparities. Single individuals in Jordan and those with lower family income in Palestine and Lebanon reported notably higher challenges. Female students in Iraq and Lebanon perceived greater challenges compared to males. Students pursuing diplomas in Jordan and bridging programs in Lebanon faced elevated difficulties. Governmental university students in Lebanon and private university students in Jordan encountered distinct challenges. Lack of available internet was particularly challenging in Jordan and Lebanon, whereas students using tablets in Lebanon and laptops in Palestine reported heightened challenges. Economic disparities, notably in family income, further hindered engagement with online learning materials. Across countries, academic challenges included managing coursework and accessing resources, exacerbated by administrative inefficiencies, especially in Palestine and Lebanon. Students in the UAE reported fewer challenges, facilitated by robust internet infrastructure and comprehensive institutional support. CONCLUSION: This study provides critical insights into the challenges faced by nursing students during the Middle East's online learning transition. Key challenges encompass technological issues, academic workload, and administrative inefficiencies, with significant disparities across countries. The findings underscore the urgent need for targeted interventions, particularly in Palestine, to enhance online learning experiences. Policymakers and educational institutions can leverage these insights to advocate for student-centric approaches and policy development aimed at improving online learning across the region.

Intravenous Immunoglobulins Alone for the Desensitization of Lung Transplant Recipients with Preformed Donor Specific Antibodies and Negative Flow Cytometry Crossmatch.

BACKGROUND: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach. METHODS: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models. RESULTS: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups. CONCLUSION: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.

Experimental data on filtration-consolidation dewatering kinetics of different cassava flours.

Dewatering is a critical step in cassava flours processing. Compression dewatering kinetics are useful to understand and design a dewatering operation. The dataset presents dewatering kinetics measured in a filtration-consolidation cell at constant pressure between 4 and 21 bar, on several cassava mashes (three batches fragmented at two particle size distributions (PSDs)). The dataset comprises, for each dewatering kinetic measurement, filtrate mass, cake height, data to estimate the pressure applied on the product (i.e. air pressure, compression force) as a function of time; and the moisture content measurements of the fresh and dewatered cassava and of the filtrate. A commented python script is included to read the dewatering experimental files and plot the kinetics Furthermore, the dataset extends its utility by including particle size distributions (PSDs) obtained from six cassava batches, subjected to several protocol variants. These data are useful for understanding the phenomena involved in cassava dewatering. They also serve as a valuable resource for researchers, designers, and operators to design cassava dewatering.

Impact of Helicobacter pylori Eradication on Surgical Treatment of Peptic Ulcer Disease: Systematic Review.

Peptic ulcer disease (PUD) poses a significant global healthcare challenge, with an intricate interplay between stomach acid-pepsin levels and mucosal protective mechanisms. The emergence of Helicobacter pylori (H. pylori) as a major etiological factor revolutionized the therapeutic landscape, highlighting the importance of bacterial eradication in PUD management. Surgical intervention remains vital, particularly in cases of perforated peptic ulcers, despite a shift towards conservative approaches. Understanding the impact of H. pylori eradication on surgical outcomes is crucial for optimizing PUD management. This systematic review was conducted to assess how H. pylori eradication treatment impacts surgical results in patients with PUD. The criteria for inclusion involved research studies on individuals aged 18 years and older with a diagnosis of PUD that necessitated surgical treatment. Important results comprised eradication rates, complications after surgery, recurrence rates, and overall outcomes for patients. Two researchers independently screened and extracted data from electronic databases using a thorough search strategy. The evaluation of quality employed standardized instruments for randomized controlled trials and cohort studies. Nine research projects met the requirements for inclusion, offering information on the effectiveness of H. pylori elimination treatment on surgical results. Different rates of eradication were noted, with a notable number of patients experiencing postoperative complications. Recurrence of ulcers was a concern, despite treatment, emphasizing the complexity of PUD management. Studies have shown that eradication therapy is effective in certain patient groups, like young men with perforated peptic ulcers. Still, there are obstacles, especially for patients who test negative for H. pylori and experience recurring ulcers. The integration of H. pylori eradication with surgical intervention represents a holistic approach to PUD management. Although eradication therapy has the potential to enhance surgical results, difficulties remain, requiring personalized treatment approaches that consider patients' unique characteristics and the cause of the disease. This research adds to the growing knowledge of PUD treatment, stressing the importance of proper management.

Nutritional Ketosis as a Therapeutic Approach in Critical Illness: A Systematic Review.

Critical illness encompasses the dysfunction of vital organs, the risk of death, and potential reversibility; it is a major cause of morbidity and mortality globally. The pathophysiology underlying many critical illnesses includes bioenergetic failure, inflammation, and oxidative stress. This systematic review aims to explore the use of nutritional ketosis (ketogenic feeds and exogenous ketone body administration) as a potential therapy, affecting the aforementioned pathways in patients with critical illnesses. This study was conducted, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search was conducted, systematically using PubMed, PubMed Central (PMC), Google Scholar, and the ScienceDirect databases in February 2024. The inclusion criteria were set to free full-text articles published within the past five years: human and animal studies, literature reviews, systematic reviews, meta-analyses, observational studies, randomized controlled trials, case reports, book chapters, gray literature, studies investigating adult samples, and articles in the English language. Exclusion criteria included pediatric studies as the topic has been studied more extensively in children, and this review aims to explore potential benefits in adult patients. The search was conducted through four databases; after the screening process, the remaining studies were assessed through quality appraisal tools appropriate to each study type. In the end, 11 studies were selected, including eight narrative reviews, one cohort study, one animal study, and one randomized controlled trial. The results of this review demonstrated that nutritional ketosis has potential safe and effective benefits for humans and animals. Nutritional ketosis shows therapeutic benefits for a vast variety of complications commonly associated with critical illness, status epilepticus, sepsis, viral infections, and glycemic control. In the end, both randomized and nonrandomized clinical trials are necessary for more conclusive findings.

The radio anatomical arrangement of nerve roots at L3 level in cauda equina sac is it affected by diseases?

An observational study to discover the common conditions affecting the lumbosacral region that may affect lumbosacral position and tension. All the patients, underwent MRI exaamination (magnetic resonance imaging) in the supine position, were examined by the same consultant radiologist. The article was revised by the institutional ethical approval committee. The position of the nerve roots was observed, and the number of nerve roots was calculated anterior to a line passing between the mid-transvers process of L3(third lumbar vertebra). The number of nerve roots ahead of this line was calculated by the radiologist at the level of the right intervertebral foramen and at the left one. This procedure was applied to the normal group, and 5 common pathological diseases were repeated including single-level lumbar disc prolapse, multiple-disc prolapse, multiple bulge, spinal stenosis and spondylolisthesis (at the level of L45 (fourth to fifth lumbar vertebrae) or L5S1 (fifth lumbar to first sacral vertebrae) being outside the study area, i.e., L3). We noticed significant difference in the number of the nerve roots between the cases with herniated discs, spinal stenosis, and spondylolisthesis with the normal group and the significance was in ascending increment in significance being the highest in cases with spondylolisthesis, and even in the groups of other pathologies which are statistically not significant, we noticed that the significance is proportional to the severity of the disease being the least in single level cases (p 0.427), to be more significant on cases with multiple prolapses(p 0.319) to be more in cases with multiple bulges to start to be statistically significant in herniated, higher significance in cases with spinal stenosis to be the highest in cases with spondylolisthesis.

COVID-19 vaccine and non-syndromic orofacial clefts in five arab countries. A case-control study.

OBJECTIVES: Risk factors for non-syndromic orofacial cleft (NSOFCs) include genetic profile and environmental exposure to medication and illnesses during pregnancy. We assessed the association between the COVID-19 vaccination and the incidence of NSOFC across five Middle Eastern countries. MATERIALS AND METHODS: This multi-country, hospital-based, case-control study included infants with NSOFCs whose first 3 intrauterine months coincided with the time when pregnant women were allowed to receive COVID-19 vaccination in the countries participating in the study. Newborns with NSOFCs were examined for cleft type and their parents were interviewed for maternal exposures and COVID-19 vaccination. Controls were newborns matched to cases in gender and setting. RESULTS: The study recruited 977 (348 children with NSOFCs and 629 controls). Maternal use of nicotine (Adjusted Odds Ratio (AOR): 2.437; P = 0.044) and family history of NSOFC (AOR: 11.059; P < 0.001) increased significantly the AOR of having a child with NSOFC. On the other hand, COVID-19 vaccine administration to pregnant mothers have significantly decreased the AOR of having a child with NSOFC (AOR: 0.337; P = 0.006). CONCLUSION: This study suggests that COVID-19 vaccination is not related to NSOFC and might protect against having a child affected with such a congenital anomaly. CLINICAL RELEVANCE: The finding of this study is important for healthcare providers for considering COVID-19 vaccination for pregnant woman. Clear communication and education about the potential risks and benefits would be crucial for informed decision-making. The study's results would directly impact pregnant individuals, as they would need accurate information to make informed decisions about their health and the health of their infants.

Advanced Chronic Kidney Disease (CKD) in a Patient With Alstrom Syndrome.

Alstrom syndrome is an autosomal recessive disease. It affects multiple systems, including cardiovascular, renal, endocrine, and eyes. Our patient is a 25-year-old female who presented with elevated creatinine. Her past medical history was significant for hypothyroidism, polycystic ovarian syndrome, blindness, cataracts, hearing loss, and heart problems. She had genetic testing done that revealed that she was homozygous for the ALMS1 gene and was diagnosed with Alstrom syndrome. She was followed by nephrology in the clinic and had chronic kidney disease (CKD) stage V. The patient traveled to Italy and was lost to follow-up.

Functionalized fennel extract-mediated alumina/cerium oxide nanocomposite potentiometric sensor for the determination of diclofenac sodium medication.

The current work suggests a new, ultrasensitive green functionalized sensor for the determination of anti-inflammatory medication diclofenac sodium (DCF). Alumina (Al2O3) and cerium oxide (CeO2) nanoparticles (NPs) have attracted great interest for their use as outstanding and electroactive nanocomposite in potentiometric and sensory research due to their ultrafunctional potential. The formed nanoparticles have been confirmed using various spectroscopic and microscopic techniques. The fennel extract-mediated Al2O3/CeO2 nanocomposite (Al2O3/CeO2 NCS) modified coated wire membrane sensor developed in this study was used to quantify DCF in bulk and commercial products. Diclofenac sodium was coupled with phosphomolybdic acid (PMA) to generate diclofenac phosphomolybdate (DCF-PM) as an active ion-pair in the existence of polyvinyl chloride (PVC) and o-nitrophenyl octyl ether (o-NPOE). Clear peaks at 270, and 303 nm with band gaps of 4.59 eV and 4.09 eV were measured using UV-vis spectroscopy of Al2O3 and CeO2, respectively. The crystallite sizes of the formed nanoparticles were XRD-determined to be 30.13 ± 8, 17.72 ± 3, and 35.8 ± 0.5 nm for Al2O3, CeO2, and Al2O3/CeO2 NCS, respectively. The developed sensor showed excellent response for the measurement and assay of DCF, with a linearity between 1.0 × 10-9 and 1.0 × 10-2 mol L-1. EmV = (57.76) log [DCF] +622.69 was derived. On the other hand, the typical type DCF-PM presented a potentiometric response range of 1.0 × 10-5-1.0 × 10-2 mol L-1 and a regression equation of EmV = (56.97) log [DCF]+367.16. The functionalized sensor that was proposed was successful in determining DCF in its commercial tablets with percent recovery 99.95 ± 0.3. Method validation has been used to improve the suitability of the suggested potentiometric technique, by studying various parameters with respect to the international council harmonization requirements for analytical methodologies.

Prevalence and Risk Factors of Cardiovascular Disease in Chronic Kidney Disease Patients at King Abdulaziz University Hospital (KAUH).

BACKGROUND: Chronic kidney disease (CKD) has emerged as a significant global health concern, with its incidence doubling over the past three decades. Cardiovascular diseases (CVD) pose a major threat to CKD patients, surpassing the risk of progressing to end-stage renal disease. While previous studies worldwide have shed light on this association, limited research has been conducted in Saudi Arabia regarding this burden. This study aims to fill this gap by identifying the prevalence and risk factors of CVD in CKD patients at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, between 2017 and 2022. METHODS: A six-year retrospective review of medical records at KAUH was conducted, including 465 non-end-stage CKD patients aged 30 to 79. Data, including demographics, clinical information, and laboratory results, were collected and statistically analyzed to investigate the association between variables. RESULTS: Out of 465 CKD patients, 262 (56.3%) were diagnosed with CVD, with congestive heart failure and ischemic heart disease being the most common types. The majority were male 259 (55.7%), non-Saudi 278 (59.8%), and aged 60 years and older 291 (62.6%). Hypertension 394 (84.7%) and diabetes mellitus 336 (72.3%) were prevalent comorbidities. Severely reduced left ventricular ejection fraction, proteinuria, diabetes mellitus, and higher BMI were identified as significant risk factors for CVD in CKD patients. CONCLUSION: This research contributes valuable insights into the prevalence and risk factors of CVD in CKD patients in Saudi Arabia, emphasizing the need for early detection and intervention. The identified risk factors provide a basis for developing targeted preventive strategies to mitigate this population's CVD burden.

Effect of prosthetic management and its timing on otological and audiological outcomes in infants with cleft lip and palate: A clinical trial.

PURPOSE: To evaluate how prosthetic management affects the otological and audiological state of infants with cleft lip and palate by preventing or treating otitis media (OM). MATERIALS AND METHODS: Thirty infants with cleft lip and palate (L/P) were assigned to three equal groups according to the age of prosthetic intervention; Group I: immediately after birth, Group II: 2 months old, Group III: 5 months old. Assessment of middle ear function by tympanometry and hearing quality by auditory brainstem response (ABR) under natural sleep was conducted before and after prosthetic treatment every month till 10 months of age. Data from the study groups were compared. RESULTS: No statistically significant differences were found between Gp I and Gp II in the 2nd, 3rd, and 4th months for right and left ears (p > 0.05). In the 5th month, statistically significant differences between the three groups were found in tympanometry for right (p = 0.011) and left (p = 0.024) ears also, in ABR for right (p = 0.007) and left (p = 0.011) ears. Tympanometric readings starting from the 6th till the 10th month showed no statistically significant differences between the three groups (p >0.05). The final ABR outcomes of the 10th month indicated statistically significant differences between the three groups for both ears (p = 0.027). CONCLUSIONS: Early prosthetic care could delay the development of OM, so it could potentially improve the otological and audiological state in infants with cleft L/P. However, prosthetic treatment may not be able to completely prevent or eliminate middle ear disorders.

Insulin-like growth factor 1 and sex hormones for assessment of anthropometric and pubertal growth of Egyptian children and adolescents with type 1 diabetes mellitus (single center study).

BACKGROUND: This study aimed to assess the anthropometric measures and pubertal growth of children and adolescents with Type 1 diabetes mellitus (T1DM) and to detect risk determinants affecting these measures and their link to glycemic control. PATIENTS AND METHODS: Two hundred children and adolescents were assessed using anthropometric measurements. Those with short stature were further evaluated using insulin-like growth factor 1 (IGF-1), bone age, and thyroid profile, while those with delayed puberty were evaluated using sex hormones and pituitary gonadotropins assay. RESULTS: We found that 12.5% of our patients were short (height SDS < -2) and IGF-1 was less than -2 SD in 72% of them. Patients with short stature had earlier age of onset of diabetes, longer duration of diabetes, higher HbA1C and urinary albumin/creatinine ratio compared to those with normal stature (p < 0.05). Additionally, patients with delayed puberty had higher HbA1c and dyslipidemia compared to those with normal puberty (p < 0.05). The regression analysis revealed that factors associated with short stature were; age at diagnosis, HbA1C > 8.2, and albumin/creatinine ratio > 8 (p < 0.05). CONCLUSION: Children with uncontrolled T1DM are at risk of short stature and delayed puberty. Diabetes duration and control seem to be independent risk factors for short stature.

Oral health status of Egyptian children with lysosomal storage diseases: An evaluation of dental indices, salivary cytokines level, and bacterial bioburden.

BACKGROUND: Lysosomal storage diseases (LSDs), a group of inborn errors of metabolism, include various subtypes, for example, mucopolysaccharidosis (MPS) and Gaucher disease (GD). Besides the physical/mental disabilities, they suffer from several oral deteriorations. AIM: To evaluate the oral health status of Egyptian children with LSD. DESIGN: Thirty LSD children and thirty non-LSD children were enrolled for this study according to the inclusion and exclusion criteria. Dental indices were used to assess caries prevalence and periodontal status. Saliva samples were collected from all enrolled children to estimate interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and protein levels as well as Streptococcus mutans and Lactobacilli colony counts. RESULTS: Children with MPS and GD showed non-significant differences in decayed, missing, or filled teeth (DMFT) scores (p = .115). Scores of dmft showed a significant increase in MPS, but not in GD children (p = .020, p = .127). Children with LSD showed significantly increased Modified Gingival Index (MGI), Plaque Index (PI), Oral Hygiene Index (OHI-s) scores (p < .001) and salivary IL-6 and TNF-α (p = .007, p = .001, p < .0001, p = .002, respectively) and salivary total proteins (p = .001) levels. Unexpectedly, non-significant differences were observed in salivary Streptococcus mutans or Lactobacilli counts in children with MPS and GD (p = .058, p = .420, p = .502, p = .053, respectively). CONCLUSION: To our knowledge, this is the first article that evaluates Egyptian children with LSD. We demonstrated high caries prevalence in primary teeth, not permanent teeth, in children with MPS and poor gingival/hygiene status in children with MPS and GD, which triggered a state of inflammation. The daily supplement intake prevented oral bacterial growth. The most probable cause of oral alterations is decreased salivary flow rate, as deduced from a significantly increased salivary protein.

The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group.

Purpose: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. Methods: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. Results: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). Conclusions: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

Vilazodone Alleviates Neurogenesis-Induced Anxiety in the Chronic Unpredictable Mild Stress Female Rat Model: Role of Wnt/ß-Catenin Signaling.

Defective ß-catenin signaling is accompanied with compensatory neurogenesis process that may pave to anxiety. ß-Catenin has a distinct role in alleviating anxiety in adolescence; however, it undergoes degradation by the degradation complex Axin and APC. Vilazodone (VZ) is a fast, effective antidepressant with SSRI activity and 5-HT1A partial agonism that amends somatic and/or psychic symptoms of anxiety. Yet, there is no data about anxiolytic effect of VZ on anxiety-related neurogenesis provoked by stress-reduced ß-catenin signaling. Furthermore, females have specific susceptibility toward psychopathology. The aim of the present study is to uncover the molecular mechanism of VZ relative to Wnt/ß-catenin signaling in female rats. Stress-induced anxiety was conducted by subjecting the rats to different stressful stimuli for 21 days. On the 15th day, stressed rats were treated with VZ(10 mg/kg, p.o.) alone or concomitant with the Wnt inhibitor: XAV939 (0.1 mg/kg, i.p.). Anxious rats showed low ß-catenin level turned over by Axin-1 with unanticipated reduction of APC pursued with elevated protein levels of neurogenesis-stimulating proteins: c-Myc and pThr183-Erk likewise gene expressions of miR-17-5p and miR-18. Two weeks of VZ treatment showed anxiolytic effect figured by alleviation of hippocampal histological examination. VZ protected ß-catenin signal via reduction in Axin-1 and elevation of APC conjugated with modulation of ß-catenin downstream targets. The cytoplasmic ß-catenin turnover by Axin-1 was restored by XAV939. Herein, VZ showed anti-anxiety effect, which may be in part through regaining the balance of the reduced ß-catenin and its subsequent exaggerated response of p-Erk, c-Myc, Dicer-1, miR-17-5p, and miR-18.