Post-transcriptional regulation of BIRC5/survivin expression and induction of apoptosis in breast cancer cells by tristetraprolin.

Inhibition of apoptosis is one of the hallmarks of cancer and is a target of various therapeutic interventions. BIRC5 is an inhibitor of apoptosis that is aberrantly expressed in cancer leading to sustained growth of tumours. Post-transcriptional control mechanisms involving RNA-binding proteins and AU-rich elements (AREs) are fundamental to many cellular processes and changes in the expression or function of these proteins can promote an aberrant and pathological phenotype. BIRC5 mRNA has an ARE in its 3' UTR making it a candidate for regulation by the RNA binding proteins tristetraprolin (TTP) and HuR (ELAVL1). In this study, we investigated the binding of TTP and HuR by RNA-immunoprecipitation assays and found that these proteins were associated with BIRC5 mRNA to varying extents. Consequently, BIRC5 expression decreased when TTP was overexpressed and apoptosis was induced. In the absence of TTP, BIRC5 mRNA was stabilized, protein expression increased and the number of apoptotic cells declined. As an ARE-mRNA stabilizing protein, recombinant HuR led to upregulation of BIRC5 expression, whereas HuR silencing was concomitant with downregulation of BIRC5 mRNA and protein and increased cell death. Survival analyses demonstrated that increased TTP and low BIRC5 expression predicted an overall better prognosis compared to dysregulated TTP and high BIRC5. Thus, the results present a novel target of ARE-mediated post-transcriptional regulation.

Extent of exposure to scented candles and prevalence of respiratory and non-respiratory symptoms amongst young university students.

BACKGROUND: Incense burning such as scented candles are commonly used in Arabian Gulf regions as it is thought to produce relaxing effects on people's mood. This study is conducted to examine the prevalence of scented candles' usage, extent of exposure and its effects on individuals' health based on symptoms prevalence in young university students. MATERIAL AND METHOD: A cross-sectional study was conducted on university students from different regions in Saudi Arabia. Data was collected in March 2020 using an online questionnaire survey adapted from The European Community Respiratory Health Survey-II (ECRHS-II). Inclusion criterion for recruitment was students with non-smoking status. Descriptive statistics were used to report demographic data on the extent of exposure to scented candles (in terms of frequency and duration) and the presence of symptoms. Multiple logistic regression analysis was used to assess the relationship between scented candles exposure and respiratory and other health-related problems. RESULTS: The prevalence of scented candles usage was 65.7% (472/718) among the respondents. However, its pervasiveness was significantly higher in females than in male respondents (74.9% vs. 28.4%; p = 0.0001). Among the scented candle users, 34.8% of the respondents used the scented candles more than 4 times a month and 40.2% of the respondents lit the scented candles for 20-40 min. A total of 117 (24.8%) respondents reported health-related problem and the top three health problems were headache 72 (15.2%), shortness of breath 42 (8.9%) and cough 37 (7.8%). The scented candle usage 5-6 times a week showed significantly lower wheezing (OR = 0.10, 95%CI 0.02-0.54, p = 0.008). The duration of more than 60 min of scented candle exposure showed higher occurrence of headache 1.42 times (95% CI = 0.68-2.96), sneezing 1.29 times (95% CI = 0.42-4.00) and wheezing 1.23 times (95% CI = 0.48-3.13), though the association was not significant. CONCLUSION: The results show that scented candle usage is more prevalent among female university students in Saudi Arabia. The common health-related problems associated with scented candle exposure were headache, shortness of breath and coughing.

Changes in the patterns of respiratory support and incidence of bronchopulmonary dysplasia; a single center experience.

BACKGROUND: With the advances in neonatal intensive care, the survival rate of extremely preterm infants is increasing. However, bronchopulmonary dysplasia (BPD) remains a major cause of morbidity among infants in this group. This study examined the changes in respiratory support modalities, specifically heated humidified high-flow nasal cannula (HHHFNC), and their association with BPD incidence among preterm infants born at < 29 weeks of gestation. METHOD: This population-based retrospective cohort study included infants born at < 29 weeks of gestation between 2016 and 2020. Data regarding the use and duration of respiratory support modalities were obtained, including mechanical ventilation, continuous positive airway pressure, HHHFNC, and low-flow oxygen therapy. Additionally, the incidence of BPD was determined in the included infants. Trend analysis for each respiratory support modality and BPD incidence rate was performed to define the temporal changes associated with changes in BPD rates. In addition, a logistic regression model was developed to identify the association between BPD and severity grade using HHHFNC. RESULTS: Three Hundred and sixteen infants were included in this study. The use and duration of HHHFNC therapy increased during the study period. Throughout the study period, the overall incidence of BPD was 49%, with no significant trends. The BPD rate was significantly higher in the infants who received HHHFNC than in those who did not (52% vs. 39%, P = 0.03). Analysis of BPD severity grades showed that both grade 1 BPD (34% vs. 21%, P = 0.03) and grade 2 BPD (12% vs. 1%, P < 0.01) were significantly more common among infants who received HHHFNC than among those who did not. In contrast, the incidence of grade 3 BPD was lower in infants who received HHFNC (6% vs. 17%, P < 0.01). The duration in days of HHHFNC was found to significantly predict BPD incidence (OR 1.04 [95%CI: 1.01-1.06], P < 0.01) after adjusting for confounding variables. CONCLUSION: The use of HHHFNC in extremely preterm infants born at < 29 weeks of gestation is increasing. There was a significant association between the duration of HHHFNC therapy and the development of BPD in extremely preterm infants born at < 29 weeks of gestation.

Elevated level of creatine phosphokinase in newborn: Clinical significance and association with congenital muscle diseases.

OBJECTIVES: To establish the normal Creatine phosphokinase (CPK) range in newborns of all 3 modes of delivery and prove that high CPK level in neonates is not specific a indicator for muscular pathology. METHODS: This is a prospective cohort study that is conducted in King Abdulaziz Medical City and King Abdullah Specialized Children Hospital in Riyadh and included 504 term neonates who were born between March 2021 and August 2021. Two hundred and fifty three were males and 251 were females. Data and consents were managed and collected using 2 coordinators. RESULTS: Duration of the second stage of labor, age on the first CPK test and fetal gestational age were significantly correlated with CPK values (r=0.197, r=-0.234, r=0.274, respectively). The normal ranges for each delivery type were 334 U/L-2667U/L in normal spontaneous vaginal delivery, 265U/L-1182U/L in elective cesarean section, and 223U/L-3082 U/L in emergency cesarean section. CONCLUSION: The CPK was elevated in all neonates in all 3 modes of deliveries. An elevated levels of CPK in neonates is not a specific indicator for any congenital muscular pathology.

The effects of non-pharmaceutical interventions on SARS-CoV-2 transmission in different socioeconomic populations in Kuwait: a modeling study.

BACKGROUND: Aggressive non-pharmaceutical interventions (NPIs) may reduce transmission of SARS-CoV-2. The extent to which these interventions are successful in stopping the spread have not been characterized in countries with distinct socioeconomic groups. We compared the effects of a partial lockdown on disease transmission among Kuwaitis (P1) and non-Kuwaitis (P2) living in Kuwait. METHODS: We fit a modified metapopulation SEIR transmission model to reported cases stratified by two groups to estimate the impact of a partial lockdown on the effective reproduction number ([Formula: see text]). We estimated the basic reproduction number ([Formula: see text]) for the transmission in each group and simulated the potential trajectories of an outbreak from the first recorded case of community transmission until 12 days after the partial lockdown. We estimated [Formula: see text] values of both groups before and after the partial curfew, simulated the effect of these values on the epidemic curves and explored a range of cross-transmission scenarios. RESULTS: We estimate [Formula: see text] at 1·08 (95% CI: 1·00-1·26) for P1 and 2·36 (2·03-2·71) for P2. On March 22nd, [Formula: see text] for P1 and P2 are estimated at 1·19 (1·04-1·34) and 1·75 (1·26-2·11) respectively. After the partial curfew had taken effect, [Formula: see text] for P1 dropped modestly to 1·05 (0·82-1·26) but almost doubled for P2 to 2·89 (2·30-3·70). Our simulated epidemic trajectories show that the partial curfew measure greatly reduced and delayed the height of the peak in P1, yet significantly elevated and hastened the peak in P2. Modest cross-transmission between P1 and P2 greatly elevated the height of the peak in P1 and brought it forward in time closer to the peak of P2. CONCLUSION: Our results indicate and quantify how the same lockdown intervention can accentuate disease transmission in some subpopulations while potentially controlling it in others. Any such control may further become compromised in the presence of cross-transmission between subpopulations. Future interventions and policies need to be sensitive to socioeconomic and health disparities.

Clinical and functional significance of tumor/stromal ATR expression in breast cancer patients.

BACKGROUND: Most breast cancer-associated fibroblasts (CAFs) are active and important cancer-promoting cells, with significant impact on patient prognosis. Therefore, we investigated here the role of the protein kinase ATR in breast stromal fibroblasts in the prognosis of locally advanced breast cancer patients. METHODS: We have used immunohistochemistry to assess the level of ATR in breast cancer tissues and their adjacent normal tissues. Immunoblotting as well as quantitative RT-PCR were utilized to show the role of breast cancer cells and IL-6 as well as AUF-1 in downregulating ATR in breast stromal fibroblasts. Engineered human breast tissue model was also used to show that ATR-deficient breast stromal fibroblasts enhance the growth of breast cancer cells. RESULTS: We have shown that the protein kinase ATR is downregulated in cancer cells and their neighboring CAFs in breast cancer tissues as compared to their respective adjacent normal tissues. The implication of cancer cells in ATR knockdown in CAFs has been proven in vitro by showing that breast cancer cells downregulate ATR in breast fibroblasts in an IL-6/STAT3-dependent manner and via AUF-1. In another cohort of 103 tumors from locally advanced breast cancer patients, we have shown that absence or reduced ATR expression in tumoral cells and their adjacent stromal fibroblasts is correlated with poor overall survival as well as disease-free survival. Furthermore, ATR expression in CAFs was inversely correlated with tumor recurrence and progression. CONCLUSION: ATR downregulation in breast CAFs is frequent, procarcinogenic, and correlated with poor patient survival.

Reduction of severe intraventricular hemorrhage, a tertiary single-center experience: incidence trends, associated risk factors, and hospital policy.

OBJECTIVES: To determine the incidence, trends, maternal and neonatal risk factors of severe intraventricular hemorrhage (IVH) among infants born 24-32 weeks and/or < 1500 g, and to evaluate the impact of changing of hospital policies and unit clinical practice on the IVH incidence. STUDY DESIGN: Retrospective chart review of preterm infants with a gestational age (GA) of 24-326 weeks and/or weight of < 1500 g born at King Abdulaziz Medical City-Riyadh (KAMC-R), Saudi Arabia, from 2016 to 2018. Multivariate logistic regression model was constructed to determine the probability of developing severe IVH and identify associations with maternal and neonatal risk factors. RESULTS: Among 640 infants, the overall incidence of severe IVH was 6.4% (41 infants), and its rate decreased significantly, from 9.4% in 2016 to 4.5% and 5% in 2017 and 2018 (p = 0.044). Multivariate analysis revealed that caesarian section delivery decreased the risk of severe IVH in GA group 24-27 weeks (p = 0.045). Furthermore use of inotropes (p = 0.0004) and surfactant (p = 0.0003) increased the risk of severe IVH. Despite increasing use of inotropes (p = 0.024), surfactant therapy (p = 0.034), and need for delivery room intubation (p = 0.015), there was a significant reduction in the incidence of severe IVH following the change in unit clinical practice and hospital policy (p = 0.007). CONCLUSION: Cesarean section was associated with decreased all grades of IVH and severe IVH, while use of inotropes was associated with increased severe IVH. The changes in hospital and unit policy were correlated with decreased IVH during the study period.

Gene therapy of hematological disorders: current challenges.

Recent advances in genetic engineering technology and stem cell biology have spurred great interest in developing gene therapies for hereditary, as well as acquired hematological disorders. Currently, hematopoietic stem cell transplantation is used to cure disorders such as hemoglobinopathies and primary immunodeficiencies; however, this method is limited by the availability of immune-matched donors. Using autologous cells coupled with genome editing bypasses this limitation and therefore became the focus of many research groups aiming to develop efficient and safe genomic modification. Hence, gene therapy research has witnessed a noticeable growth in recent years with numerous successful achievements; however, several challenges have to be overcome before gene therapy becomes widely available for patients. In this review, I discuss tools used in gene therapy for hematological disorders, choices of target cells, and delivery vehicles with emphasis on current hurdles and attempts to solve them, and present examples of successful clinical trials to give a glimpse of current progress.

An atypical pulmonary fibrosis is associated with co-inheritance of mutations in the calcium binding protein genes S100A3 and S100A13.

BACKGROUND: Pulmonary fibrosis is one of the leading indications for lung transplantation. The disease, which is of unknown aetiology, can be progressive, resulting in distortion of the extracellular matrix (ECM), inflammation, fibrosis and eventual death. METHODS: 13 patients born to consanguineous parents from two unrelated families presenting with interstitial lung disease were clinically investigated. Nine patients developed respiratory failure and subsequently died. Molecular genetic investigations were performed on patients' whole blood or archived tissues, and cell biological investigations were performed on patient-derived fibroblasts. RESULTS: The combination of a unique pattern of early-onset lung fibrosis (at 12-15 years old) with distinctive radiological findings, including 1) traction bronchiectasis, 2) intralobular septal thickening, 3) shrinkage of the secondary pulmonary lobules mainly around the bronchovascular bundles and 4) early type 2 respiratory failure (elevated blood carbon dioxide levels), represents a novel clinical subtype of familial pulmonary fibrosis. Molecular genetic investigation of families revealed a hypomorphic variant in S100A3 and a novel truncating mutation in S100A13, both segregating with the disease in an autosomal recessive manner. Family members that were either heterozygous carriers or wild-type normal for both variants were unaffected. Analysis of patient-derived fibroblasts demonstrated significantly reduced S100A3 and S100A13 expression. Further analysis demonstrated aberrant intracellular calcium homeostasis, mitochondrial dysregulation and differential expression of ECM components. CONCLUSION: Our data demonstrate that digenic inheritance of mutations in S100A3 and S100A13 underlie the pathophysiology of pulmonary fibrosis associated with a significant reduction of both proteins, which suggests a calcium-dependent therapeutic approach for management of the disease.

Differences in Stability, Activity and Mutation Effects Between Human and Mouse Leucine-Rich Repeat Kinase 2.

Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene have been implicated in the pathogenesis of Parkinson's disease (PD). Identification of PD-associated LRRK2 mutations has led to the development of novel animal models, primarily in mice. However, the characteristics of human LRRK2 and mouse Lrrk2 protein have not previously been directly compared. Here we show that proteins from different species have different biochemical properties, with the mouse protein being more stable but having significantly lower kinase activity compared to the human orthologue. In examining the effects of PD-associated mutations and risk factors on protein function, we found that conserved substitutions such as G2019S affect human and mouse LRRK2 proteins similarly, but variation around position 2385, which is not fully conserved between humans and mice, induces divergent in vitro behavior. Overall our results indicate that structural differences between human and mouse LRRK2 are likely responsible for the different properties we have observed for these two species of LRRK2 protein. These results have implications for disease modelling of LRRK2 mutations in mice and on the testing of pharmacological therapies in animals.

Identification of a novel genetic locus underlying tremor and dystonia.

BACKGROUND: Five affected individuals with syndromic tremulous dystonia, spasticity, and white matter disease from a consanguineous extended family covering a period of over 24 years are presented. A positional cloning approach utilizing genome-wide linkage, homozygozity mapping and whole exome sequencing was used for genetic characterization. The impact of a calmodulin-binding transcription activator 2, (CAMTA2) isoform 2, hypomorphic mutation on mRNA and protein abundance was studied using fluorescent reporter expression cassettes. Human brain sub-region cDNA libraries were used to study the expression pattern of CAMTA2 transcript variants. RESULTS: Linkage analysis and homozygozity mapping localized the disease allele to a 2.1 Mb interval on chromosome 17 with a LOD score of 4.58. Whole exome sequencing identified a G>A change in the transcript variant 2 5'UTR of CAMTA2 that was only 6 bases upstream of the translation start site (c.-6G > A) (NM_001171166.1) and segregated with disease in an autosomal recessive manner. Transfection of wild type and mutant 5'UTR-linked fluorescent reporters showed no impact upon mRNA levels but a significant reduction in the protein fluorescent activity implying translation inhibition. CONCLUSIONS: Mutation of CAMTA2 resulting in post-transcriptional inhibition of its own gene activity likely underlies a novel syndromic tremulous dystonia.

A Prospective Study on the Incidence and Outcomes of Neonatal Thrombocytopenia at a Tertiary Care Facility in Central Saudi Arabia.

BACKGROUND: The incidence of neonatal thrombocytopenia is low, yet highly dependent on the populations studied. PURPOSE: To assess the incidence of neonatal thrombocytopenia and identify factors associated with its outcomes, namely time to disease onset, recovery duration, and platelet count. METHODS: A prospective observational study was conducted between May and October 2013 at a large tertiary care facility in Saudi Arabia. Neonates with a platelet count of fewer than 150,000/µL of blood were followed up until their recovery or death. RESULTS: The period incidence of neonatal thrombocytopenia was 84/4379 (1.9%). The mortality rate associated with the condition was 68/100,000 births. The male-female ratio of neonates with thrombocytopenia was 2.4:1. The mean (standard deviation) time to disease onset was 1.83 (1.29) days, whereas that of recovery duration was 15.35 (18.46) days. The mean (standard deviation) platelet count at onset was 109,543 (32,826)/µL of blood, whereas that of the increase in platelet count from onset to recovery was 121,876 (78,218)/µL of blood. Treatment comprised monitoring/spontaneous recovery (n = 52, 64.2%) or platelet transfusion (n = 9, 11.1%), immunoglobulins (n = 8, 9.9%), or a combination of both (n = 12, 14.8%). Neonates with a higher gestational age (ß = 8061, t = 2.456) and late disease onset (ß = 26,178, t = 3.969) were more likely to have a larger increase in platelet count from onset to recovery than those with a lower gestational age (adjusted P = .017) and earlier disease onset (adjusted P < .001). IMPLICATIONS: The high incidence of neonatal thrombocytopenia in this Middle Eastern setting indicates that it may be dependent on the population studied. Special attention should be focused on neonates of lower gestational ages and with an early disease onset, because their platelet count recovery may be slower than that of the countergroup.

Professionals' Attitude Toward Reporting Child Sexual Abuse in Saudi Arabia.

Child sexual abuse (CSA) requires specialized knowledge and training that includes forensic interview skills. The aim of this study was to determine variations in professionals' attitudes toward CSA by measuring three aspects of forensic attitudes (sensitivity, specificity, and skepticism) and evaluating disagreements concerning the assessment of CSA cases in Saudi Arabia. A cross-sectional, web-based study, in which the Child Forensic Attitude Scale was used to measure professionals' attitudes, was conducted. Professionals who dealt with suspected cases of CSA as part of their jobs or were in professions that necessitated involvement with such cases, were selected as participants. Of 327 participants, 53% were aged ≤40 years, and 54% were men. In addition, 24% were doctors/nurses, 20% were therapists/psychiatrists, 24% were social workers, 17% were educators, 9% were law enforcement professionals, and 5% were medical examiners. Attitude subscale scores differed significantly according to participants' sex, specialty, and training. Women, healthcare professionals, and those who had participated in more than five training courses were more concerned about the underreporting of abuse (high sensitivity) relative to other professionals. In comparison, men, medical examiners, law enforcement officers, and undertrained professionals tended to underreport suspected sexual abuse cases (high specificity). High specificity in attitudes toward suspected cases of CSA could affect professionals' judgment and contribute to low reporting rates. Certain strategies, including increasing self-awareness of personal bias, specific CSA recognition courses, and team approaches to case assessment and management, should be implemented to control the influence of subjective factors.

Screening for glucose-6-phosphate dehydrogenase deficiency in neonates: a comparison between cord and peripheral blood samples.

BACKGROUND: The use of cord blood in the neonatal screening for glucose-6-phosphate dehydrogenase (G6PD) deficiency is being done with increasing frequency but has yet to be adequately evaluated against the use of peripheral blood sample which is usually employed for confirmation. We sought to determine the incidence and gender distribution of G6PD deficiency, and compare the results of cord against peripheral blood in identifying G6PD DEFICIENCY neonates using quantitative enzyme activity assay. METHODS: We carried out a retrospective and cross-sectional study employing review of primary hospital data of neonates born in a tertiary care center from January to December 2008. RESULTS: Among the 8139 neonates with cord blood G6PD assays, an overall incidence of 2% for G6PD deficiency was computed. 79% of these were males and 21% were females with significantly more deficient males (p < .001). Gender-specific incidence was 3.06% for males and 0.85% for females. A subgroup analysis comparing cord and peripheral blood samples (n = 1253) showed a significantly higher mean G6PD value for peripheral than cord blood (15.12 ± 4.52 U/g and 14.52 ± 4.43 U/g, respectively, p = 0.0008). However, the proportion of G6PD deficient neonates did not significantly differ in the two groups (p = 0.79). Sensitivity of cord blood in screening for G6PD deficiency, using peripheral G6PD assay as a gold standard was 98.6% with a NPV of 99.5%. CONCLUSION: There was no difference between cord and peripheral blood samples in discriminating between G6PD deficient and non-deficient neonates. A significantly higher mean peripheral G6PD assay reinforces the use of cord blood for neonatal screening since it has substantially low false negative results.

Evaluation of pollen germination of some palm males and pollination impact on bunch weight and fruit quality in Kadary date palm cultivar (Phoenix dactylifera L.).

The present study was carried out during two successive seasons (2013-2014) at the Research and Agriculture Experiment Station, Dirab, College of Food and Agricultural Sciences, King Saud University, Riyadh. Pollen grains, used in this trial, were collected from eleven male, namely Succary, Menify, Sallag, Dikhiny, Nabout Zamel, Serry, Khalas, Shagra, Safry, Maktumi and Kadary in order to pollinate female Kadary date palm cultivar. Results indicated that pollens of Safry male followed by Succary, Menify and Serry males increased the physical and biochemical characteristics of fruits during both seasons. Also, all the studied characters were significantly affected with different pollen males used in this trial. Pollens of Safry male gave highest fruit retention and bunch weight and best fruit quality like fruit and flesh weight, fruit size and fruit length and fruit biochemical properties as compared with other male. In vitro pollen germination of eleven males was studied using various concentration of sucrose (4, 6, 8 and 10%). The results showed that best germination was achieved with 8% sucrose concentration; however, 10% sucrose resulted in reduced percentage of pollen germination. In addition, pollen tube growth of five males (Succary, Sallag, Nabout-Zamel, Khalas and Safry) at 8% sucrose was alsostudied at 2, 4, 6 and 24 hr time interval. Elongation rate of pollen tube increased significantly after 24 hrs and it was found that pollens of Safry male gave highest pollen tube growth after 24 hrs than pollens of other male.

Blepharo-cheilo-dontic (BCD) syndrome: expanding the phenotype, case report and review of literature.

The combination of lagophthalmia, euryblepharon, ectropion of lower eyelids, distichiasis, bilateral cleft lip and palate, and oligodontia comprises the blepharo-cheilo-dontic (BCD) syndrome. This combination has been found sporadically or with positive family history and inherited as an autosomal dominant condition with variable expression. We described a Saudi boy with the cardinal signs consistent with the BCD syndrome. In addition to the common components of BCD syndrome that involve eyelids, lip, and teeth abnormalities, this patient is the third reported BCD case with imperforate anus, the second with thyroid agenesis, and the first with lumbosacral meningomyelocele.

Sustained stabilization of Interleukin-8 mRNA in human macrophages.

The mRNAs of most inflammatory mediators are short-lived due to AU-rich elements (AREs) in their 3'-untranslated regions. AREs ensure a low basal level of expression during homeostasis and a transient nature of expression during the inflammatory response. Here, we report that the mRNA of the pro-inflammatory chemokine IL-8, which contains an archetypal ARE, is unexpectedly constitutively abundant and highly stable in primary human monocytes and macrophages. Using the pre-monocyte-like THP-1 cell line that can differentiate into macrophage-like cells, we show that a low level of unstable IL-8 mRNA in undifferentiated cells (half-life<30 min) becomes constitutively elevated and the mRNA is dramatically stabilized in differentiated THP-1 cells with a half-life of more than 15 h similar to primary monocytes and macrophages. In contrast, the level and stability of TNF-α mRNA also containing an ARE is only slightly affected by differentiation; it remains low and unstable in primary macrophages and differentiated THP-1 cells with an estimated half-life of less than 20 min. This differentiation-dependent stabilization of IL-8 mRNA is p38 MAPK-independent and is probably coupled with reduced protein translation. Reporter assays in THP-1 cells suggest that the ARE alone is not sufficient for the constitutive stabilization in macrophage-like cells and imply an effect of the natural biogenesis of the transcript on the stabilization of the mature form. We present a novel, cell type-dependent sustained stabilization of an ARE-containing mRNA with similarities to situations found in disease.

Retrospective Comparative Analysis of Neonatal Mortality and Morbidity in Preterm Singleton and Multiple Births -Single Center Experience.

Objective. To compare mortality and major neonatal morbidities between singleton preterm infants and preterm infants of multiple gestations born <33 weeks' gestation. Method. Case-control study of preterm multiples and singletons <33 weeks' born at King Abdul-Aziz Medical City Riyadh (KAMC-R) between January 2017 and December 2020. Out-born infants and infants with lethal congenital abnormalities were excluded from the study. Mortality and major neonatal morbidities including bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), sepsis and surgical necrotizing enterocolitis (NEC) were compared between preterm singletons and multiples. Results. A total of 803 preterm infants were included: 567 (70.6%) were singletons, 158 (19.6%) were twins and 36 (4.5%) infants were higher multiples. Adjusted mortality before hospital discharge was significantly higher among preterm infants of multiple gestations compared to preterm singletons (12.3% vs 7.9%; P = .003; AOR, 2.2; 95% CI, 1.3-3.7). Retinopathy of prematurity (ROP) needing treatment was significantly higher among preterm infants of multiple pregnancies compared to preterm singletons (11% vs 6.5%, P = .033, AOR 1.1, 95% CI, 1.04-2.99). In addition, the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks post menstrual age (PMA) (29.7% vs 20.5%; P = .003; AOR, 1.7; 95% CI, 1.2-2.5) and culture positive sepsis (24.2% vs 17.5%; P = .044; AOR, 1.5; 95% CI, 1.01-2.2) were significantly higher among preterm infants of multiple pregnancy. There were no differences in mortality and adverse neonatal outcomes between twins and higher multiples. Conclusion. Preterm infants of multiple gestations suffered higher mortality and neonatal morbidities compared to preterm singleton infants despite a higher utilization of maternal antenatal steroids and better antenatal care.

Role of Psychosomatic Medicine in Complex Medical Cases: A Case Study of a Patient With Breast Cancer Who Refused Mastectomy.

Psychosomatic medicine has been known to play a pivotal role in the management of complex medical cases by providing a bridge between the physical disease and psychological distress. This case study focuses on a 42-year-old Saudi female diagnosed with breast cancer and generalized anxiety disorder. In addition to anxiety, the patient had a history of obsessive-compulsive personality traits, which contributed to her reluctance to undergo mastectomy. Significant challenges and noncompliance with treatment were caused by her unwillingness and inadequate interaction with the medical team. An integrated multidisciplinary strategy including psycho-oncological interventions was necessary because of the complexity of this case. Communication issues were addressed through the concerted efforts of the specialist teams. A comprehensive patient-practitioner understanding was established, which enabled the teams to persuade the patient to undergo surgical intervention. Overcoming her initial resistance, the patient eventually complied with the treatment plan, leading to a successful surgery. Postsurgical evaluations using the Hamilton Anxiety Scale indicated a significant reduction in anxiety levels. This case underscores the critical contribution of psychosomatic medicine to healthcare, especially in challenging situations that demand additional resource allocation, further highlighting the importance of an interdisciplinary approach, efficient communication, and patient-practitioner rapport in healthcare outcomes.

Accuracy of Gonial Angle Measurements Using Panoramic Imaging versus Lateral Cephalograms in Adults with Different Mandibular Divergence Patterns.

Introduction: Gonial angle is an important craniofacial parameter providing information about symmetry and vertical dimensions of the facial skeleton. It can be measured on panoramic radiographs and lateral cephalograms. Reliable assessment of the gonial angle is challenged by the superimpositions associated with lateral cephalograms. The aim of the current study was to assess the precision of panoramic imaging in measuring the gonial angles compared to lateral cephalograms in adult patients with different mandibular divergence patterns. Methods: Panoramic radiographs and lateral cephalograms of 448 adults (18-30 years old) were utilized in the study. The gonial angle was determined on the lateral cephalograms using an online AI-driven assessment tool (WebCephTM) and compared to the panoramic measurements among the different gender, malocclusion, and mandibular divergence groups. Results: Statistically significant differences were recorded between measurements taken on lateral cephalograms or panoramic radiographs (p=0.022). In addition, statistically significant differences were reported in gonial angle measurements on panoramic radiographs among the different mandibular divergence groups (p=0.004) for FMA (p=0.002) for Sn-GoMe. Conclusion: While cephalometry is considered the gold standard tool for reliable gonial angle assessment, panoramic radiographs were more accurate in detecting the differences between the divergence groups in the current study.