Variations in the Root Form and Root Canal Morphology of Permanent Mandibular canine.

BACKGROUND: Mandibular canines are recognized as usually having one root and one root canal in most cases. However, many investigators have reported the anatomical variations associated with mandibular canines. Thus; the objective of this study is to determine the number of roots and morphology of the root canal system of permanent mandibular canine in a Nepalese population. METHODS: Cone Beam Computerized Tomography images of 390 patients in a Nepalese population were selected, and a total of 780 mandibular canines were analyzed. The number of root and the canal configurations were investigated. Data were analyzed with descriptive analysis and Chi-square tests using the Statistical Package for the Social Sciences (SPSS) software version 20 (SPSS Inc, Chicago, IL, USA). RESULTS: Out of the 780 mandibular canines, 741(95%) were single-rooted canines while only 39 (5%) were double-rooted canines. The most common type of Vertucci in single-rooted canines was Type I (1-1) in the percentage of 85.6% and the least type was Type IV (1-2) in the percentage of (2.5%). The Chi-square tests showed no significant association between gender and number of roots (P = 0.87) and gender and root canal configuration in single-rooted canine (P = 0.52). CONCLUSIONS: All mandibular permanent canines were single rooted but 5.2% of the permanent mandibular canines had two roots.

Recent advances in the treatment of primary and secondary progressive Multiple Sclerosis.

BACKGROUND: The article highlights upcoming potential treatments, which target different phases of inflammation and offer remyelinating strategies as well as direct and indirect neuroprotective and oligodendrocyte protective effects, providing a hopeful outlook for patients with primary and secondary progressive multiple sclerosis (PPMS and SPMS). OBJECTIVES: The review aims to identify potential treatments and ongoing clinical trials for PPMS and SPMS, and compare their mechanisms of action, efficacy, and side effects with current treatments. METHODS: We reviewed ongoing clinical trials for PPMS and SPMS on the NIH website, as well as articles from PubMed, Embase, and clinicaltrails.gov since 2010. RESULTS: BTKIs like, tolebrutinib, and fenebrutinib are being explored as potential PMS treatments. Vidofludimus calcium, an orally available treatment, has shown a reduction of active and new MRI lesions. Other treatments like simvastatin, N-acetylcysteine (NAC), and alpha-lipoic acid are being explored for their antioxidant properties. AHSCT and mesenchymal stem cell therapy are experimental options for younger patients with high inflammatory activity. CONCLUSIONS: SPMS and PPMS are being studied for new treatments and future trials should consider combination therapies targeting inflammation, demyelination, and neuronal death, as the pathogenesis of PMS involves complex factors.

Traumatic Injury among Patients Presenting to the Department of Emergency Medicine of a Tertiary Care Centre.

Introduction: The majority of trauma-related deaths occur in low- and middle-income countries; however, limited data exists in these settings related to injury types and severity. The prevalence of trauma similar to our setting was less estimated. This study aimed to find the prevalence of traumatic injury among patients presented to the department of emergency medicine of a tertiary care centre. Methods: This is a descriptive cross-sectional study conducted among patients presented to the Department of Emergency Medicine from 15 September 2021 to 14 September 2022. Ethical approval was taken from the Institutional Review Committee. World Health Organization trauma minimum data set, injury mechanism, types and patient disposition data were collected and injury severity scores were calculated. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 47,825 patients, 1,524 (3.19%) (3.03-3.34, 95% Confidence Interval) patients presented with a traumatic injury. A total of 967 (63.45%) were males and had a median age of 30 years (Interquartile range: 25). Most injuries were caused by falls 650 (42.65%), followed by road traffic accidents 411 (26.97%). A majority had minor Injury Severity Scores 1280 (83.99%). Conclusions: The prevalence of traumatic injury among patients presenting to emergency was found to be lower than other studies done in similar settings. Keywords: emergency care; injuries and wounds; injury severity score; trauma unit.

Diagnostic journey and multimodal management of a rare urogenital rhabdomyosarcoma with rectovaginal fistula in an adolescent: a case report.

Introduction and importance: Rhabdomyosarcoma is a malignant tumour that originates from immature muscle cells and belongs to the category of soft-tissue sarcomas. It is predominantly diagnosed in children under the age of 6. This condition can manifest within the genitourinary tract and may exhibit non-specific symptoms such as changes in bowel habits and fever. Early detection and a comprehensive, multidisciplinary approach are essential to achieving more favourable outcomes. This report highlights an uncommon case of urogenital rhabdomyosarcoma in a 15-year-old girl, in addition to the presence of a rectovaginal fistula. Case presentation: A 15-year-old girl with presented with fever, altered bowel habits, and a lump in her lower abdomen, abdominal discomfort, and incomplete bowel evacuation. She also had faecal discharge from the vagina. Diagnostic imaging and biopsy confirmed urogenital rhabdomyosarcoma with a rectovaginal fistula. The patient is currently undergoing induction chemotherapy and is scheduled for radiation therapy and surgery. Clinical discussion: Rhabdomyosarcoma is a rare paediatric oncologic concern due to its aggressive nature and potential metastasis. The presentation varies based on age, tumour location, and metastasis presence. This patient presented with altered bowel habits, a pelvic mass and unusual feculent discharge, suggesting a rectovaginal fistula. Diagnostic imaging confirmed the diagnosis, and induction chemotherapy led to a positive response and reduced tumour size. Conclusion: Urogenital rhabdomyosarcoma is an aggressive malignancy with non-specific symptoms, making early diagnosis challenging. An accurate diagnosis requires high suspicion, imaging, and a biopsy. Multidisciplinary management, including surgery, chemotherapy, and radiation therapy, improves outcomes and improves paediatric patients' prognosis and quality of life.

Autoimmune and paraneoplastic neurological disorders: A review of relevant neuroimaging findings.

INTRODUCTION: Paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis (AIE) are immune-mediated disorders. PNS is linked to cancer, while AIE may not Their clinical manifestations and imaging patterns need further elucidation. OBJECTIVE/AIMS: To investigate the clinical profiles, antibody associations, neuroimaging patterns, treatments, and outcomes of PNS and AIE. METHODS: A systematic review of 379 articles published between 2014 and 2023 was conducted. Of the 55 studies screened, 333 patients were diagnosed with either PNS or AIE and tested positive for novel antibodies. Data on demographics, symptoms, imaging, antibodies, cancer associations, treatment, and outcomes were extracted. RESULTS: The study included 333 patients (mean age 54 years, 67% males) with PNS and AIE positive for various novel antibodies. 84% had central nervous system issues like cognitive impairment (53%), rhombencephalitis (17%), and cerebellar disorders (24%). Neuroimaging revealed distinct patterns with high-risk antibodies associated with brainstem lesions in 98%, cerebellar in 91%, hippocampal in 98%, basal ganglia in 75%, and spinal cord in 91%, while low/intermediate-risk antibodies were associated with medial temporal lobe lesions in 71% and other cortical/subcortical lesions in 55%. High-risk antibodies were associated with younger males, deep brain lesions, and increased mortality of 61%, while low/intermediate-risk antibodies were associated with females, cortical/subcortical lesions, and better outcomes with 39% mortality. Associated cancers included seminomas (23%), lung (19%), ovarian (2%), and breast (2%). Treatments included IVIG, chemotherapy, and plasmapheresis. Overall mortality was 25% in this cohort. CONCLUSION: PNS and AIE have distinct clinical and radiological patterns based on antibody profiles. High-risk antibodies are associated with increased mortality while low/intermediate-risk antibodies are associated with improved outcomes. Appropriate imaging and antibody testing are critical for accurate diagnosis.

Long-Term Artificial Selection for Increased Larval Body Weight of Hermetia illucens in Industrial Settings.

Black soldier fly (Hermetia illucens) farming has exponentially increased in recent years due to the ability of its larvae to efficiently convert low-grade organic materials into high-value food, feed, and technical products. There is a need to further improve the efficiency of production, to meet the rising demands for proteins in the feed and food industries under limited resources. One means of improvement is artificial selection, which has been widely applied in plants and in other livestock species. In 2019, a genetic improvement program was started with the aim to increase larval body weight in black soldier fly larvae. In this paper, we present the outcomes of this breeding program after 10, 13, and 16 generations of selection. The performance of the selected body weight line was compared to the base population line over six experimental rounds under different environmental conditions. Under automated production settings, an average increase of +39% in larval weight, +34% in wet crate yield, +26% in dry matter crate yield, +32% in crude protein per crate, and +21% crude fat per crate was achieved in the selected line compared to the base population line. This research demonstrates the potential contribution of artificial selection to improve efficiency when farming black soldier flies in industrial settings. Further research is needed to fully unlock that potential.

Hippo pathway activity influences liver cell fate.

The Hippo-signaling pathway is an important regulator of cellular proliferation and organ size. However, little is known about the role of this cascade in the control of cell fate. Employing a combination of lineage tracing, clonal analysis, and organoid culture approaches, we demonstrate that Hippo pathway activity is essential for the maintenance of the differentiated hepatocyte state. Remarkably, acute inactivation of Hippo pathway signaling in vivo is sufficient to dedifferentiate, at very high efficiencies, adult hepatocytes into cells bearing progenitor characteristics. These hepatocyte-derived progenitor cells demonstrate self-renewal and engraftment capacity at the single-cell level. We also identify the NOTCH-signaling pathway as a functional important effector downstream of the Hippo transducer YAP. Our findings uncover a potent role for Hippo/YAP signaling in controlling liver cell fate and reveal an unprecedented level of phenotypic plasticity in mature hepatocytes, which has implications for the understanding and manipulation of liver regeneration.

Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer.

Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here, we show that YAP, the downstream target of the tumor-suppressive Hippo-signaling pathway regulates miRNA biogenesis in a cell-density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA-processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding posttranscriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer.

Restriction of intestinal stem cell expansion and the regenerative response by YAP.

A remarkable feature of regenerative processes is their ability to halt proliferation once an organ's structure has been restored. The Wnt signalling pathway is the major driving force for homeostatic self-renewal and regeneration in the mammalian intestine. However, the mechanisms that counterbalance Wnt-driven proliferation are poorly understood. Here we demonstrate in mice and humans that yes-associated protein 1 (YAP; also known as YAP1)--a protein known for its powerful growth-inducing and oncogenic properties--has an unexpected growth-suppressive function, restricting Wnt signals during intestinal regeneration. Transgenic expression of YAP reduces Wnt target gene expression and results in the rapid loss of intestinal crypts. In addition, loss of YAP results in Wnt hypersensitivity during regeneration, leading to hyperplasia, expansion of intestinal stem cells and niche cells, and formation of ectopic crypts and microadenomas. We find that cytoplasmic YAP restricts elevated Wnt signalling independently of the AXIN-APC-GSK-3ß complex partly by limiting the activity of dishevelled (DVL). DVL signals in the nucleus of intestinal stem cells, and its forced expression leads to enhanced Wnt signalling in crypts. YAP dampens Wnt signals by restricting DVL nuclear translocation during regenerative growth. Finally, we provide evidence that YAP is silenced in a subset of highly aggressive and undifferentiated human colorectal carcinomas, and that its expression can restrict the growth of colorectal carcinoma xenografts. Collectively, our work describes a novel mechanistic paradigm for how proliferative signals are counterbalanced in regenerating tissues. Additionally, our findings have important implications for the targeting of YAP in human malignancies.

Cnn1 inhibits the interactions between the KMN complexes of the yeast kinetochore.

Kinetochores attach the replicated chromosomes to the mitotic spindle and orchestrate their transmission to the daughter cells. Kinetochore-spindle binding and chromosome segregation are mediated by the multi-copy KNL1(Spc105), MIS12(Mtw1) and NDC80(Ndc80) complexes that form the so-called KMN network. KMN-spindle attachment is regulated by the Aurora B(Ipl1) and MPS1(Mps1) kinases. It is unclear whether other mechanisms exist that support KMN activity during the cell cycle. Using budding yeast, we show that kinetochore protein Cnn1 localizes to the base of the Ndc80 complex and promotes a functionally competent configuration of the KMN network. Cnn1 regulates KMN activity in a spatiotemporal manner by inhibiting the interaction between its complexes. Cnn1 activity peaks in anaphase and is driven by the Cdc28, Mps1 and Ipl1 kinases.