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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.

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.

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.

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.

Introduction: Academic stress is prevalent among pharmacy students. Several factors such as hectic schedules, courses and exam load as well as lack of recreational time during semester have been reported as determinants of academic stress. Studies revealed; the use of aroma oils especially with relaxant properties may help ease stress. Methods: This study aimed to investigate the effect of lavender oil on academic stress during exams in pharmacy students. A randomized-single-blind placebo-controlled trial providing aromatherapy with lavender oil as an intervention was conducted in male pharmacy students. The outcomes assessed included stress, stool pattern, headache and vital signs that comprised of systolic, diastolic blood pressure (SBP and DBP) and heart rate (HR). The study was approved from concerned authority and registered in ClinicalTrials.gov (NCT#03460626). Results: The placebo and experimental group showed a significant (p 0.05) and, at post-exam time-point (p > 0.05). Conclusion: Aromatherapy with lavender oil did not have any effect on academic stress. Trial registration: The study was registered prospectively on ClinicalTrials.gov (NCT#03460626) on 19th February 2018. Keywords: Academic stress, Pharmacy students, Aromatherapy, Randomized controlled trial, Lavender, Exam stress, Heart rate, Blood pressure

The mandate of the Covenant of important issues given by the Kings Assyrians attention and clear through careful selection of the crown prince during their lives, in order to avoid wrestling, which might occur between their children in order to ascend the throne of the Assyrian after their death, and despite what Attention and importance those kings gave to this matter, failure However, it was an ally of some of them, as is the case with all of the King (Sennacherib) (704-681 BC. m), and King (Esarhaddon) (680-669 BC. m), which they had set the young their children in the position of crown prince on others their children account older; because of their love to their children who are chosen in this position of love feelings , as submission to the wishes of (pure - Zakoto), the second wife and mother first.

The Relations Of Babylonian - Egyptian At Babylonian modern era(626 to 539 BC). Tension and hostility because of competition that took place between the two parties, for control of the Levant (the country Haty in Babylonian texts) that poses this region of the importance of economic for the two countries, especially Babylonia, which was in dire need of raw materials like ( wood and stone and metal) necessary that you use in construction projects Urban by the Babylonians Kings This is in addition to the Medes and later The Alakhmanin who controlled the trade routes located on the northern front and north-eastern means depriving State Babylonian sources of raw materials, which was obtained by the Kings Assyrians from this area in the past, so the face of all of King Nbobasr and his son King Nebuchadnezzar his attention to the Western Front (Syria, Palestine and the Lebanese coast and East Jordan) to compensate for this shortfall in raw materials. It seems the events that Egyptians who aspire also in control of the region have realized from the first glance aspirations Babylonian king Nbobasr toward the Levant so stood with Assyria all have the power to save Assyria from falling by the Babylonians and Medes perhaps under an agreement between the parties is that their attempts went unheeded, as the Babylonians with their allies succeeded the Medes in the destruction of the Assyrian state. After that, the Babylonians tightly controlled the Levant through military campaigns, carried out by each of the King Nbobasr and King Nebuchadnezzar II in order to ensure the subordination of their state, and the Egyptian stand against greed. Even managed Nebuchadnezzar II in one of his military campaigns of inflicting a crushing defeat in Egypt what persuaded Egypt's Pharaoh Ahmose II apart from the Levant to devote himself to the conditions of his country's domestic deteriorating so experienced political relations from the reign of this pharaoh with the successors of King Nebuchadnezzar II breakthrough in the relationship, particularly in the reign of the last Babylonian king period Enbaunid saw his clear affinity between the two countries, and the close ties of friendship and culminated in the Treaty contract between the parties in order to stand against the Persian ambitions. We have tried through this research highlight the natural political relations that prevailed between the Babylonian and Egyptian depending on what was in the historical texts of old, which seems to which the economic factor has had an important role in the outbreak of hostility between the two sides, In conclusion I hope I have and hyped in my humble,and from God reconciled.

Abstract Hepatitis C virus (HCV) is the leading cause of chronic hepatitis worldwide and its subtypes/genotypes are clinically important for clinical management and vaccine development. The present study describes frequency distribution of different HCV genotypes and their treatment status in HCV RNA positive patients from district Swat. A total of 185 HCV infected sera were analyzed by molecular genotyping assay. The most prevalent genotype was 3a (34.1%), followed by 2a (8.1%), 3b (7%) and 1a (5.4%). The samples found untypable by the present method of genotypes was 37.8% while, patients with mixed genotype infections were 7.6%. More than 80% of untypable cases were from those HCV patients who had received interferon plus ribavirin standard therapy in the past and either were non-responders and were relapsed thereafter or were under treatment. In conclusion, genotype 3a is the most prevalent HCV genotype in the region. A high prevalence rate of untypable genotypes is present in treated patients that need further investigation for the successful genotyping by developing new assays or using viral sequencing method.

Abstract Six major Hepatitis C virus (HCV) genotypes and hundreds of subtypes have been identified globally. All these genotypes are generally studied for epidemiology, their vaccine development and clinical management. This article comments the frequency distribution of various HCV genotypes circulate in different areas/districts of Khyber Pakhtoonkhaw Province of Pakistan. Sum of 415 HCV RNA PCR positive sera samples were tested by a molecular genotyping assay. Data analysis revealed that out of these 415 HCV RNA positive patients 243 were males and 172 were females. Distribution breakup of the patients was 135, 58, 51, 51, 36, 32, 6, 7and 9 patients come from the districts of Abbottabad, Mardan, Pehawar, Swat, Haripure, Swabi and Dera Ismail Khan, respectively. Out of the tested samples, genotype specific PCR fragments were observed in 299 (74.82%) patient serum samples. The distribution of genotypes of the typeable samples was as fallows: 3 patients (0.72%) each were infected with genotype 1a and genotype 1b; 240 patients (80.26%) of genotype 3a; 25 patients (6.00%) genotype 3b; and 28 patients (6.73%) were observed as with mixed genotypic infection. Sums of 116 serum samples (27.88%) were still found untypeable by the used molecular genotyping system. In conclusion, HCV genotypes 1a, 1b, 3a and 3b are distributed in various parts of KPK among which the genotype 3a is the most frequent genotype.