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Abstract Background Studies did not recommend which position for implant overdenture poses the lowest biomechanical risk and the least chance of peri-implant bone loss and ridge resorption for those who might need a mandibular two-implant overdenture. The study objectives were to investigate the impact of implant position, in lateral incisors or canine positions, on peri-implant bone loss and posterior ridge resorption. Methods Fifty patients with mandibular two-implants were recalled and divided according to the implant position into two groups (group L: implants in lateral incisor positions and group C: implants in canine positions). The circumferential peri-implant bone level and posterior ridge resorption were assessed at implant insertion (T0), one year later (T1), and five years later (T5) using the follow-up CBCT. Data were analyzed using the Statistical Package of Social Science (SPSS) program. A Mann-Whitney test was used to compare two different groups. Paired groups were compared using the Wilcoxon signed-rank test. The threshold of significance is fixed at a 5% level (p-value). Results Significant differences in the vertical bone loss between groups appeared at (T5 - T1) (Mann Whitney test, (P = 0.01)) and at (T5 - T0) (Mann Whitney test, (P = 0.005)), and a significant difference in horizontal bone loss between groups was found at (T1 - T0) (Mann Whitney test, (P = 0.041)) and (T5 - T1) (Mann Whitney test, (P = 0.041)). Also, there were significant differences over the evaluation period between groups at certain points along the ridge at M1 (Mann Whitney test, (P = 0.021)), M3 (Mann Whitney test, (P = 0.008)), and M4 (Mann Whitney test, (P = 0.015)). Conclusions According to the findings of this clinical study, the placement of implants in the lateral incisor position for two implant-retained overdentures is a viable choice. In comparison to the canine position, the lateral incisor position demonstrated superior peri-implant responses, which could potentially enhance the longevity of the implants. Furthermore, the placement of implants in the lateral incisor position can promote a more even distribution of stress and help mitigate posterior ridge resorption. Conversely, implants in the canine position may cause a seesaw effect and result in greater posterior ridge resorption. Clinical Trial Registry Number (NCT06055842) (13/03/2024).

The insular cortex, a critical hub in the brain’s sensory, cognitive, and emotional networks, remains an intriguing subject of study. In this article, we discuss its intricate functional neuroanatomy, emphasizing its pivotal role in processing olfactory information. Through concise exploration, we delve into the insula’s diverse connectivity and its involvement in sensory integration, particularly in olfaction. Stimulation studies in humans reveal compelling insights into the insula’s contribution to the perception of smell, hinting at its broader implications for cognitive processing. Additionally, we explore an avenue of research in which studying olfactory processing via insular stimulation could unravel higher-level cognitive processes. This innovative approach could help give a fresh perspective on the interplay between sensory and cognitive domains, offering valuable insights into the neural mechanisms underlying cognition and emotion. In conclusion, future research efforts should emphasize a multidisciplinary approach, combining advanced imaging and surgical techniques to explore the intricate functions of the human insula. Moreover, awake craniotomies could offer a unique opportunity for real-time observation, shedding light on its neural circuitry and contributions to higher-order brain functions. Furthermore, olfaction’s direct cortical projection enables precise exploration of insular function, promising insights into cognitive and emotional processes. This multifaceted approach will deepen our understanding of the insular cortex and its significance in human cognition and emotion.

Abstract The ability to model physiological systems through 3D neural in-vitro systems may enable new treatments for various diseases while lowering the need for challenging animal and human testing. Creating such an environment, and even more impactful, one that mimics human brain tissue under mechanical stimulation, would be extremely useful to study a range of human-specific biological processes and conditions related to brain trauma. One approach is to use human cerebral organoids (hCOs) in-vitro models. hCOs recreate key cytoarchitectural features of the human brain, distinguishing themselves from more traditional 2D cultures and organ-on-a-chip models, as well as in-vivo animal models. Here, we propose a novel approach to emulate mild and moderate traumatic brain injury (TBI) using hCOs that undergo strain rates indicative of TBI. We subjected the hCOs to mild (2 s−1) and moderate (14 s−1) loading conditions, examined the mechanotransduction response, and investigated downstream genomic effects and regulatory pathways. The revealed pathways of note were cell death and metabolic and biosynthetic pathways implicating genes such as CARD9, ENO1, and FOXP3, respectively. Additionally, we show a steeper ascent in calcium signaling as we imposed higher loading conditions on the organoids. The elucidation of neural response to mechanical stimulation in reliable human cerebral organoid models gives insights into a better understanding of TBI in humans.

IntroductionGlioblastoma multiforme (GBM) is one of the most aggressive types of brain cancer, and despite rigorous research, patient prognosis remains poor. The characterization of sex-specific differences in incidence and overall survival (OS) of these patients has led to an investigation of the molecular mechanisms that may underlie this dimorphism.MethodsWe reviewed the published literature describing the gender specific differences in GBM Biology reported in the last ten years and summarized the available information that may point towards a patient-tailored GBM therapy.ResultsRadiomics analyses have revealed that imaging parameters predict OS and treatment response of GBM patients in a sex-specific manner. Moreover, gender-based analysis of the transcriptome GBM tumors has found differential expression of various genes, potentially impacting the OS survival of patients in a sex-dependent manner. In addition to gene expression differences, the timing (subclonal or clonal) of the acquisition of common GBM-driver mutations, metabolism requirements, and immune landscape of these tumors has also been shown to be sex-specific, leading to a differential therapeutic response by sex. In male patients, transformed astrocytes are more sensitive to glutaminase 1 (GLS1) inhibition due to increased requirements for glutamine uptake. In female patients, GBM is more sensitive to anti-IL1β due to an increased population of circulating granulocytic myeloid-derived suppressor cells (gMDSC).ConclusionMoving forward, continued elucidation of GBM sexual dimorphism will be critical in improving the OS of GBM patients by ensuring that treatment plans are structured to exploit these sex-specific, molecular vulnerabilities in GBM tumors.

Background. Abnormal uterine bleeding is a broad term involving various irregularities of the menstrual cycle. Previously various terms were used to define abnormalities in menstrual bleeding. To create a universally accepted system of nomenclature, the Federation of Obstetrics and Gynecology proposed the new terminology PALM-COIEN. The current study is aimed to classify cases of abnormal uterine bleeding as per PALM-COEIN. Materials and Methods. It is a retrospective, observational study using the data from 110 patients, who underwent hysteroscopic evaluation and endometrial biopsy and were categorized based on PALM-COIEN. Patients were grouped under these categories after detailed history, examination, investigations, hysteroscopic findings, and histopathology. Results. Polyp was the commonest group (n=45, 40.9%) in our study, which was followed by leiomyoma (n=30, 27.27%), ovulatory disturbances (n=28, 25.45%), adenomyosis (n=5, 4.54%), malignancy (n=2, 1.81%) respectively. Conclusions. Hysteroscopic evaluation is a simple and useful tool to find out the structural pathologies of PALM-COIEN classification. Further histopathological confirmation of clinical diagnosis can enhance the diagnosis and treatment modalities.

Glioblastoma (GBM) is fatal and the study of therapeutic resistance, disease progression, and drug discovery in GBM or glioma stem cells is often hindered by limited resources. This limitation slows down progress in both drug discovery and patient survival. Here we present a genetically engineered human cerebral organoid model with a cancer-like phenotype that could provide a basis for GBM-like models. Specifically, we engineered a doxycycline-inducible vector encoding shRNAs enabling depletion of the TP53, PTEN, and NF1 tumor suppressors in human cerebral organoids. Designated as inducible short hairpin-TP53-PTEN-NF1 (ish-TPN), doxycycline treatment resulted in human cancer-like cerebral organoids that effaced the entire organoid cytoarchitecture, while uninduced ish-TPN cerebral organoids recapitulated the normal cytoarchitecture of the brain. Transcriptomic analysis revealed a proneural GBM subtype. This proof-of-concept study offers a valuable resource for directly investigating the emergence and progression of gliomas within the context of specific genetic alterations in normal cerebral organoids.

Soft tissue sarcomas (STS) invading the skull base are rare with little data to guide surgical management. Here we aimed to determine the factors affecting tumor control rates and survival in patients with T4 stage head and neck STS involving the skull base. A retrospective review of STS patients, surgically treated at our institution between 1994 and 2017 was conducted. Variables were collected and assessed against progression-free survival. Tumors were graded using the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system. A total of 51 patients (mean age of 35) were included, of whom 17 (33.3%) patients were FNCLCC grade 1, 8 (15. 7%) were FNCLCC grade 2 and 26 (51%) were FNCLCC grade 3. The median PFS was 236.4 months while the 5- and 10-year PFS rates were 44% and 17%, respectively. Recurrence occurred in 17 (33.3%) patients. Local recurrence occurred in 10 (58.8%). Univariate analysis revealed R0 resection had a near-significant impact on tumor control in radiation-naïve patients. Otherwise, prior radiation (HR 6.221, CI 1.236–31.314) and cavernous sinus involvement (HR 14.464, CI 3.326–62.901) were negative predictors of PFS. The most common cause of treatment failure was local recurrence. In T4 stage head and neck STS with skull-base involvement, FNCLCC grade, radiation status, and anatomic spread should be considered in determining the overall treatment strategy.

Background. Due to the harmful effects resulting from the addition of antibiotics to treat diseases affecting poultry and their use as growth promoter, it was necessary to have safe alternatives such as organic acids and probiotics, which work to provide an appropriate pH for activity of beneficial bacteria and reducing the numbers of harmful pathogenic bacteria. Objective. To assess the effects of dietary supplementation of probiotics, with or without organic acids (acetic, propionic, and benzoic) on growth performance, carcass quality, digestibility, intestinal development, gut microbiota, and serum parameters of broiler chicks. Methodology. A total number of 250 one-day old, unsexed Ross (308) broiler chicks, were equally assigned to five feeding treatments (50 birds/treatment, five replicates of ten birds/treatment) as follows: T1 (control); fed a basal diet (BD), T2; fed BD + 2g commercial probiotics (PRO)/kg diet, T3: fed BD + 2g PRO/ kg diet + 10 ml acetic acid/kg diet, T4: fed BD + 2g PRO/kg diet + 10 ml propionic acid/ kg diet, and T5: fed BD + 2g PRO/ kg diet + 10 ml benzoic acid / kg diet. The trial prolonged from day 1 to day 42 of age. Results. Compared to the control, the results revealed that body weight and body weight gain were significantly improved at 3 and 6 wks of age as a result of supplementing the diets with probiotics and organic acids (especially benzoic acid). The positive impacts of the supplements on FCR were more pronounced from 4-6 weeks and for the overall period (0-6 wks). No mortalities occurred when organic acids were supplemented. The tested supplements also decreased bacterial counts of ileal E. coli. Moreover, probiotics plus benzoic acid treatment (T5) significantly (P < 0.05) increased the ileal lactobacilli count. Carcass traits, internal organs and GIT histological parameters were positively affected by different treatments, especially probiotics plus benzoic acid treatment. The supplements improved ALT, AST and ALP activity and decreased cholesterol and triglycerides content in blood serum (P

Human brain organoids are models derived from human embryonic or induced pluripotent stem cells that mimic basic cerebral microanatomy and demonstrate simple functional neuronal networks. Brain organoids have been a rapidly expanding avenue for biomedical research in general and specifically: neural development, regeneration, and central nervous system pathophysiology. However, technology replicating functional aspects of the human brain, including electrically active neural networks, requires a responsible code of conduct. In this review, we focus the discussion on intrinsic and extrinsic ethical factors associated with organoids: intrinsic considerations arise with the growing complexity of human brain organoids, including human-animal chimerism, consciousness development, and questions of where these human-like beings fall in a moral hierarchy. Extrinsic considerations explore ethics on obtainment, manufacturing, and production of sophisticated human products. In summary, a thoughtful code of conduct using human brain organoids towards the advancement of science and medicine is crucial. This article shall facilitate a structured thought process approaching the moral landscape of organoid technology.

مقدمة: هناك انتشار متزايد ومخيف في تدخين النارجيلة عالمياً يجعل الدراسات حول أضرارها وخاصةً طويلة الأمد غير متناسب مع حجم المشكلة. على الرغم من أن العلاقة محسومة بين تدخين السجائر وارتفاع نسبة تطور الداء الرئوي الانسدادي المزمن وأمراض القلب والأوعية والسرطان إلا أن علاقة هذه الأمراض مع تدخين النارجيلة وبالأخص مدة وكمية التعرض غير مدروسة بشكل جيد. الهدف: الهدف من هذه الدراسة هو مقارنة قيم وظائف الرئة المقاسة بالسبيرومتر لدى المدخنين للنارجيلة حصراً وغير المدخنين وعلاقة تبدل هذه القيم بحال وجوده مع مدة التدخين ، وتحديد نسبة شيوع الداء الرئوي الانسدادي المزمن عند مدخني النارجيلة المرضى والطرائق: دراسة تحليلية مقطعية عرضانية شملت 182 شخصاً بأعمار تتراوح بين 20-60سنة من مراجعي العيادات الخارجية بمشفى تشرين الجامعي والمدخنين للنارجيلة حصراً أو غير المدخنين إطلاقاً بعد أخذ الموافقة المستنيرة وملء استبيان خاص ثم إجراء وظائف رئة لدى المجموعتين. اعتُمد برنامج IBM SSPS statistic في تحليل البيانات واعتبرت القيمة التنبؤية P-value الأقل من 0.05 هامة إحصائياً. النتائج كان متوسط قيم الحجم الزفيري القسري بالثانية الأولى (FEV1%) أخفض بشكل واضح لدى مدخني النارجيلة. لوحظ أيضاً انخفاض هام إحصائياً بقيم كل من FEV1/FVC. بلغ عدد الأشخاص المصابين بالداء الرئوي الانسدادي المزمن لدى مجموعة المدخنين 15 شخصاً (10%) وكان معدل التدخين لديهم (49.27±15.2) نارجيلة-سنة مقابل (31.1±14.93) نارجيلة-سنة عند غير المصابين P≤0.0001. الخلاصة: توصلت هذه الدراسة إلى أن تدخين النارجيلة له أهمية في تدهور وظائف الرئة وتطور الداء الرئوي الانسدادي المزمن والذي يمثل عبئاً كبيراً عالمياً على الصحة العامة.

Glioblastoma (GBM) is a malignant tumor with a median survival rate of 15-16 months with standard care; however, cases of successful treatment offer hope that an enhanced understanding of the pathology will improve the prognosis. The cell of origin in GBM remains controversial. Recent evidence has implicated stem cells as cells of origin in many cancers. Neural stem/precursor cells (NSCs) are being evaluated as potential initiators of GBM tumorigenesis. The NSCs in the subventricular zone (SVZ) have demonstrated similar molecular profiles and share several distinctive characteristics to proliferative glioblastoma stem cells (GSCs) in GBM. Genomic and proteomic studies comparing the SVZ and GBM support the hypothesis that the tumor cells and SVZ cells are related. Animal models corroborate this connection, demonstrating migratory patterns from the SVZ to the tumor. Along with laboratory and animal research, clinical studies have demonstrated improved progression-free survival in patients with GBM after radiation to the ipsilateral SVZ. Additionally, key genetic mutations in GBM for the most part carry regulatory roles in the SVZ as well. An exciting avenue towards SVZ modeling and determining its role in gliomagenesis in the human context is human brain organoids. Here we comprehensively discuss and review the role of the SVZ in GBM genesis, maintenance, and modeling.

Objectives: Adult survivors with congenital heart diseases represent a large and growing population, yet the published data does not represent the magnitude of their needs specifically in the Middle East. We aimed to review our experience at King Faisal Heart Center, Riyadh, Saudi Arabia for the outcome of adult patients with congenital heart disease who underwent either primary or redo surgery. Methods: A retrospective study at a tertiary care hospital. All patients who underwent surgery either as the first surgery or as a reoperation for congenital heart disease aged >16 years old at the time of cardiac surgery in the period between January 1, 2008 and January 1, 2013. We looked for incidence of postoperative bleeding, arrhythmias, acute kidney injury, neurological complications, duration of mechanical ventilation, hospital and intensive care unit (ICU) stay. Additionally, we assessed the mortality and 1- and 5-year survival. Results: Ninety-eight patients were included in our study. Fifty-two (53%) were females and 46 (47%) were males, with a mean age of 26 ± 8.4 years and a mean weight of 62 ± 22.8 kg. Forty-nine patients (50%) required redo surgery. Ten patients (10%) suffered from postoperative bleeding. Eight patients (8%) had postoperative arrhythmias, of which two patients required permanent pacemaker insertion. Three patients (3%) had postoperative acute kidney injury and seven patients (7%) suffered from neurological complications. The mean duration of ventilation was 1.3 ± 2 days, with a mean ICU and hospital stay of 3.7 ± 3 days, and 10 ± 7 days, respectively. The overall mortality rate in our series was 4% with a 1–5-year survival of 96%. Conclusion: Adult patients with congenital heart disease are prone to immediate postoperative multisystem complications, yet the majority of them are reversible. Their 1- and 5-year survival rate is excellent. Further follow up studies are required. Keywords: Adults, Congenital heart disease, Cardiac surgery, Outcome