Schizophrenia is a leading cause of global disease burden. Current drug treatments are associated with significant side-effects and have limited efficacy for many patients; highlighting the need to develop new approaches that target other aspects of the neurobiology of schizophrenia. Preclinical, in vivo imaging, post-mortem, genetic and pharmacological studies have highlighted the key role of cortical GABA-glutamatergic microcircuits and their projections to subcortical dopaminergic circuits in the pathoetiology of negative, cognitive and psychotic symptoms. Antipsychotics primarily act downstream of the dopaminergic component of this circuit. However, multiple drugs are currently in development that could target other elements of this circuit to treat schizophrenia. These include drugs for GABA or glutamatergic targets, including glycine transporters, d-amino acid oxidase, sodium channels or potassium channels. Other drugs in development are likely to primarily act on pathways that regulate the dopaminergic system such as muscarinic or trace amine receptors or serotonin 2A receptors, whilst phosphodiesterase 10 A inhibitors are being developed to modulate the downstream consequences of dopaminergic dysfunction. Our review considers where new drugs may act on this circuit and their latest clinical trial evidence in terms of indication, efficacy and side-effects. Limitations of the circuit model, including whether there are neurobiologically distinct subgroups of patients, and future directions are also considered. Several drugs based on the mechanisms reviewed have promising clinical data, with the muscarinic agonist KarXT most advanced. If they are approved for clinical use, they have the potential to revolutionise understanding of the pathophysiology and treatment of schizophrenia.

Bipolar Disorder is associated with high rates of suicidal thoughts, behaviors, and outcomes, yet the lived experience of suicidality and Bipolar Disorder is not particularly well understood. Understanding the role of psychosocial aetiologies in suicidality outcomes for those living with Bipolar Disorder is key for developing appropriately targeted interventions focusing on factors that are amenable to change. In line with PRISMA guidance, we conducted a scoping review to identify the types of psychosocial factors studied in relation to the experience of suicidality for people living with Bipolar Disorder diagnoses. Systematic literature searches identified a sample of 166 articles from which key study data were extracted and charted. A narrative synthesis of the reviewed literature is presented ordered by the factors investigated across studies, a frequency count of the types of psychological/social aetiologies studied, and a brief overview of the key findings for each aetiology. Most of the identified literature took the form of quantitative cross-sectional studies, with only one qualitative study and 18 quantitative prospective studies. The most studied aetiologies were trauma (specifically early adverse experiences and childhood traumas) and stressful life events, impulsivity (primarily subjective self-reported trait impulsivity), social support and functioning, and personality/temperament factors. Only six studies in the final sample reported basing their research questions and/or hypotheses on an explicit theoretical model of suicide. The literature was primarily focused on using self-report measurements of key aetiologies and on factors which lead to worsened suicidality rather than focusing on potentially protective or buffering factors. Future research needs to better justify the aetiologies investigated in relation to suicidality outcomes for people living with Bipolar Disorder, including a firmer basis in theory and hypothesis testing, more prospective designs, and the use of alternative assessments of psychosocial aetiologies in addition to self-report questionnaires.

Denture stomatitis (DS) is a very common disease in wearers of removable complete and partial dentures with a worldwide prevalence in the range of 20-67%. Both industrially developed and impoverished nations are affected by the illness. DS is often associated with ill-fitting dentures or a fungal infection with Candida spp. Candida is normally found in the oral cavity microbiota, but it can be harmful to the health of elderly people with underlying diseases. Therefore, the purpose of the present study is to offer the most recent information about the epidemiology, etiology, and global distribution of Candida species associated with DS through a systematic review. Several databases, including Medline, Web of Science, and Scopus, were used to conduct an extensive search of the literature published in the previous 20 years. The selection of studies was performed by two authors. The extracted data were as follows: author, year of publication, country, sample, frequency of DS, method of diagnosing stomatitis, species of Candida, risk factors, and etiology of the disease. The JBI Critical appraisal tools were used to assess the quality of the studies. Eventually, twenty-eight studies were included in the systematic review. Twenty-one studies investigated DS, while seven studies examined Candida colonization in patients using removable dentures. The results show that the main causes of DS include the type of dentures, continuous wearing of dentures, and the formation of a Candida biofilm, which is facilitated by poor dental hygiene. Additionally, previous studies have pinpointed the significance of the salivary flow, saliva composition, and salivary pH. The findings of the current review indicate that it is crucial to monitor denture wearers for the appearance of DS, especially the patients whose immunity has been impaired due to a systemic condition. Finally, frequent follow-ups should include a clinical examination and microbial swabs of the palatal mucosa and the mucosal surface of the denture.

BACKGROUND: Titanium is considered to be an inert material owing to the ability of the material to form a passive titanium oxide layer. However, once the titanium oxide layer is lost, it can lead to exposure of the underlying titanium substructure and can undergo corrosion.
CONCLUSIONS: The article explores the role of titanium ions and particles from dental implants on cells, cytokine release, and on the systemic redistribution of these particles as well as theories proposed to elucidate the effects of these particles on peri-implant inflammation based on evidence from in-vitro, human, and animal studies. Titanium particles and ions have a pro-inflammatory and cytotoxic effect on cells and promote the release of pro-inflammatory mediators like cytokines. Three theories to explain etiopathogenesis have been proposed, one based on microbial dysbiosis, the second based on titanium particles and ions and the third based on a synergistic effect between microbiome and titanium particles on the host.
CONCLUSIONS: There is clear evidence from in-vitro and limited human and animal studies that titanium particles released from dental implants have a detrimental effect on cells directly and through the release of pro-inflammatory cytokines. Future clinical and translational studies are required to clarify the role of titanium particles and ions in peri-implant inflammation and the etiopathogenesis of peri-implantitis.

OBJECTIVE: Presbyphagia is defined as structural, physiological and innervational alterations in the swallowing process as a result of aging and is considered to be involved in the etiology of dysphagia. This systematic review and meta-analysis aimed to estimate the prevalence of presbyphagia in older adults without disease-related dysphagia.
METHODS: In this study five databases were searched in October 2023 with no time limitation. Combined effect sizes of presbyphagia prevalence were calculated using random effect models. Meta-regression and subgroup analyses were conducted to identify sources of heterogeneity. Egger\'s test and a funnel plot were employed to examine publication bias.
RESULTS: A total of 19 studies were selected for analysis. Overall, the prevalence of presbyphagia in older adults was 30.8% (95% confidence interval [CI] 24.8-36.7%). Publication bias was adjusted for using the fill-and-trim method and the corrected pooled prevalence of presbyphagia was 17.3% (95% CI 11.0-23.6%). In addition, the meta-regression findings revealed that the assessment tool had significant effects upon heterogeneity.
CONCLUSIONS: Although the pooled prevalence of presbyphagia in older adults was 17.3%, the lack of large representative studies limited the interpretation of these findings. In the future, further large studies that diagnose presbyphagia using standardized assessment tools would facilitate new avenues to reduce the risk of dysphagia in older adults.

When de-novo immune-mediated thrombotic thrombocytopenic purpura (TTP) is diagnosed following an invasive procedure, clinical presentation patterns and outcomes are poorly defined. Therefore, in a systematic literature review of patients diagnosed with TTP following an invasive surgical or non-surgical procedure, we identified 19 studies reporting data on 25 patients. These data suggest that 1) TTP pathogenesis likely begins prior to the invasive procedure, 2) patients experience significant diagnostic delays, and 3) there is a high incidence of renal replacement therapy. Although invasive procedures may trigger TTP, further studies are needed to clarify the mechanisms underlying this association.

OBJECTIVE: To review the childhood risk factors for pediatric cancer (diagnosis before age 20).
METHODS: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021.
RESULTS: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy.

UNASSIGNED: Ewing sarcoma (ES) is a malignant and aggressive bony tumor affecting the most common age group of 5-20 years. It constitutes 10%-15% of all bone sarcomas and is the second most common primary malignant bone tumor after osteosarcoma. It usually presents with pain, which is typically constant and progressive in nature. The primary source of pain is due to the instability of the spine to support the weight of the body, the vertebral body\'s expanding cortices due to the growing mass, compression of nerve roots due to tumour mass, pathologic fractures, spinal cord compression, and invasion of tissue by the tumour mass.
UNASSIGNED: We reviewed the literature on Ewing\'s Sarcoma of the spine to evaluate its etiology, clinical presentations, differential diagnosis, imaging modalities and management with chemotherapy, radiotherapy, and surgical management. PubMed, EMBASE, Google Scholar and Cochrane key articles were searched. Keywords like \'Ewing\'s Sarcoma,\' \'Spine,\' \'etiology,\' \'treatment,\' \'surgical management,\' and \'en bloc resection\' were used.
UNASSIGNED: The current management of Ewing\'s sarcoma of the spine usually involves three primary modalities: combination chemotherapy, surgery and/or radiotherapy. Recent improvements in combination chemotherapy (vincristine, doxorubicin, cyclophosphamide +/- Ifosfamide and etoposide) are among the most significant factors for improving survival. Also, recent advancements in radiotherapy, instrumentation, and fusion techniques in surgical management have been demonstrated to improve local disease control and overall survival.
UNASSIGNED: Primary Ewing sarcoma of the spine is a rare condition affecting the most common age group of 5-20 years, accounting for 1-3 cases/million/year. About 5 % of cases have spine involvement. Recent improvements in combination chemotherapy have improved the overall survival rates. Enbloc resection and/or radiotherapy have improved local control of the disease.

BACKGROUND: Splenic infarction is a rare event in clinical practice, diagnosed by CT scan. There are many causes. They often determine the treatment given. However, there is no consensus on etiological investigations.
METHODS: We present here an almost systematic review of the literature, based on data available on Pubmed from 1991 to 2022. Using the keywords \"splenic infarct\", from 1893 references, 11 cohort studies and 867 clinical cases were included in this review. Articles written in languages using alphabets other than Latin were excluded.
CONCLUSIONS: Analysis of these various studies has enabled us to draw up a list that is intended to be as exhaustive as possible of the causes of splenic infarction. The most frequent are emboligenic heart disease, hematological malignancies, solid neoplasia and certain infections. The descriptions available in the literature were mainly based on isolated clinical cases, not always making it possible to establish a causal link with the disease described, especially as around 20% of reported cases of splenic infarction were asymptomatic and potentially of incidental discovery. Based on the findings of this literature review, we propose a protocol for the etiological assessment of splenic infarcts.

UNASSIGNED: According to the Global Burden of Diseases, Injuries, and Risk Factors, lower respiratory infections cause more than 2.3 million deaths globally, with a majority occurring in sub-Saharan Africa, including Ethiopia.Community-acquired pneumonia (CAP) is a major contributor to global mortality and morbidity. Understanding the prevalence and common bacterial causes of CAP is crucial for clinicians to accurately diagnose and improve patient satisfaction. The purpose of this systematic review was to report the pooled prevalence and common bacterial etiologies of CAP among adult patients in Ethiopia.
UNASSIGNED: This review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A comprehensive search of the published articles between January 2000 and October 2022 was performed using open access electronic databases such as PUBMED, Science Direct, CINAHL, HINARI, Google Scholar, and local university repositories. Cochrane Q and I2 values were used to assess heterogeneity among the studies. Publication bias was assessed using funnel plots and Egger\'s test. The random-effects model was used to estimate the pooled prevalence.
UNASSIGNED: Of all the publications that were thoroughly searched, 9 studies with 2496 participants met the criteria for analysis. All of the studies were cross-sectionally designed and most of the studies used convenient sampling techniques. The included studies consisted of two conducted among adult patients diagnosed with CAP and living with HIV/AIDS, while the remaining seven studies were conducted among adult patients diagnosed with CAP without HIV/AIDS. The combined prevalence of bacterial causes of community-acquired pneumonia (CAP) among adult patients was found to be 39.18% (CI 36.34-42.02), with an I2 of 52.6 and a P value of 0.032. The primary bacterial cause was Klebsiella pneumoniae (9.1%), followed by Streptococcus pneumoniae (8.11%), and Staphylococcus aureus (6.8%). Therefore, it is advisable to introduce a diagnostic tool for identifying specific causative agents and drug resistance, which could lead to improved treatment and better patient outcomes by reducing the need for empirical treatments.