Monckeberg's Medial Sclerosis as a Cause for Headache and Facial Pain.

PURPOSE OF REVIEW: Mönckeberg's medial sclerosis (MMS) is a chronic, non-inflammatory degenerative condition affecting primarily the tunica media of muscular arteries resulting in their calcification. The purpose of this comprehensive review is to describe MMS as it appears in the literature, in the context of headache and facial pain. Understanding the etiopathology, the associated conditions, and the differential diagnoses is important in managing MMS. RECENT FINDINGS: Management of MMS primarily depends upon identification of its associated conditions and their treatment. Due to the rare incidence and inadequate literature on MMS presenting with headaches, the diagnosis of the pain and the entity itself is challenging. MMS is characterized by associated systemic conditions and absence of inflammatory markers. It can mimic giant cell arteritis (GCA) and other pain entities. An interdisciplinary approach involving appropriate specialties is recommended.

Antipsychotic Medication in Sub-Saharan Africa: A Systematic Literature Review.

PURPOSE: There is limited evidence on the use of antipsychotic medications to treat people with schizophrenia in Sub-Saharan Africa (SSA). This systematic literature review identified original research on use of antipsychotic drugs for primary psychotic disorders in SSA, assessed the methodological quality of studies, summarized intervention strategies, and examined patient-level outcomes. METHODS: PubMed, PsychInfo, Cochrane Collaboration, African Journals Online, and CINAHL databases were searched for studies in SSA that focused on antipsychotic treatment for primary psychotic disorders and that investigated at least one patient-level outcome. Articles in English and published before April 2019 were included. Epidemiological studies, drug discontinuation studies, studies with drugs other than antipsychotics, and multicenter studies that did not specify SSA results were excluded. An adapted standardized instrument assessed methodological quality. RESULTS: Twenty-six articles were reviewed. Three levels of evidence were found: single-group reports, quasi-experimental studies, and randomized controlled trials. Study outcomes included change in psychiatric symptoms, adverse effects, remission rates, or change in functional status. Nine studies reported improvements in psychiatric symptoms with antipsychotic medication. Seven studies investigating adverse effects of antipsychotics found that they were associated with an increase in metabolic syndrome. Two studies reported that remission was achieved in most subjects, and one study reported improvements in functional status. CONCLUSIONS: Despite adverse effects, treatment with antipsychotic medications may be beneficial for individuals with primary psychotic disorders in SSA. Apart from South Africa, there is a scarcity of research on antipsychotics from countries in SSA, and there are numerous important gaps in the literature.

Evaluation and endodontic management of a patient with 6 single-rooted molars: a case report.

This case report describes a patient with unusual tooth morphology involving the bilateral presence of 6 maxillary and mandibular first and second molars with a single root and a single canal. The article also discusses the endodontic management of a single-rooted maxillary molar and the use of cone beam computed tomography for evaluation and diagnosis of these anatomical variations.

A Systematic Review of the Use of Intraoral Scanning for Human Identification Based on Palatal Morphology.

A common application for intraoral scanners is the digitization of the morphology of teeth and palatal rugae. Palatal scans are most commonly required to fabricate complete dentures and immediate transitional dentures and serve as a reference point for assessing orthodontic results. However, they are also frequently included by accident, even though the main purpose of intraoral scanning is to reconstruct dentition using computer-aided manufacturing (CAM). The literature shows that the identification of disaster victims has frequently involved palatal rugae impressions. As the skull provides sound insulation, the rugae are resistant to heat, chemicals, and stress. Antemortem data might be difficult to find during a forensic inquiry, particularly in disaster victim identification cases. In contrast with DNA and fingerprints, there is a greater likelihood of having a dental record that contains palatal scans. With specialized software, the scans can be exported as open stereolithography (STL) files. Considering that a full case consumes up to about 100 MB of hard drive space, long-term storage should not be an issue compared to a plaster model. Additionally, dentists widely use online databases to exchange data for smile design, implant registration, and orthodontic purposes. This will produce a digital database that grows quickly and is readily usable for forensic investigations. The uniqueness of forensic features is frequently challenged; however, palatal morphology's unique trait could make it possible as it is characteristic of individuals as well as the most distinguishing factor. This review will highlight how rugae, palatal morphology, mirroring, superimposition, and geometrics can serve in forensic identification.

The Efficacy of Telemental Health Interventions for Mood Disorders Pre-COVID-19: A Narrative Review.

The onset of the COVID-19 pandemic saw a significant surge in the utilization of telemental health (TMH) services. This narrative review aimed to investigate the efficacy of TMH for serious mood disorders prior to the COVID-19 pandemic. A search across databases was conducted for randomized controlled trials focusing on TMH interventions for mood disorders, encompassing major depressive disorder (MDD) and bipolar disorder (BD). Study and patient characteristics, interventions, and outcomes were extracted. From a pool of 2611 papers initially identified, 17 met the inclusion criteria: 14 focused on MDD, while 4 addressed BD. Among these, 6 papers directly compared TMH interventions to in-person of same treatment, revealing improved access to care and higher rates of appointment follow-up with TMH. Additionally, 6 papers comparing TMH to treatment as usual demonstrated improvements in mood outcomes. Conversely, 3 papers comparing different TMH interventions found no discernible differences in outcomes. Notably, 3 studies evaluated TMH as an adjunct to usual care, all reporting enhancements in depression outcomes. Overall, preliminary evidence suggests that prior to COVID-19, TMH interventions for serious mood disorders facilitated improved access to care and follow-up, with comparable clinical outcomes to traditional in-person interventions. The discussion addresses limitations and provides recommendations for future research in this domain.

The Relationship between Oral Health and Schizophrenia in Advanced Age-A Narrative Review in the Context of the Current Literature.

Schizophrenia is a psychiatric disorder that makes patients incompetent to perform day-to-day activities due to their progressing mental illness. In addition to disturbances with thoughts, behavioral changes, and impaired cognitive functions, oro-systemic health also becomes compromised. Even though the population with schizophrenia is primarily made up of older people, little is known about this group's oral health treatment. The present review explores the relationship between oral healthcare and elderly patients with schizophrenia. Our literature search included databases, like PubMed, Embase, and Google Scholar, for appropriate and evidence-based information. Preventive and management strategies outlined in the included articles and future research perspectives in this field are discussed. To the best of our knowledge, this is the first review that looked at dental care and related characteristics in older schizophrenia patients. The findings highlight the necessity for targeted dental interventions to address the dental health challenges faced by this vulnerable population. Integrating dental health into the overall medical management of elderly individuals with schizophrenia is crucial. Although specific therapies remain limited, the emphasis is on preventive dentistry to reduce the occurrence and progression of oral diseases in this group.

TIGIT Expression on Activated NK Cells Correlates with Greater Anti-Tumor Activity but Promotes Functional Decline upon Lung Cancer Exposure: Implications for Adoptive Cell Therapy and TIGIT-Targeted Therapies.

Treatments targeting TIGIT have gained a lot of attention due to strong preclinical and early clinical results, particularly with anti-PD-(L)1 therapeutics. However, this combination has failed to meet progression-free survival endpoints in phase III trials. Most of our understanding of TIGIT comes from studies of T cell function. Yet, this inhibitory receptor is often upregulated to the same, or higher, extent on NK cells in cancers. Studies in murine models have demonstrated that TIGIT inhibits NK cells and promotes exhaustion, with its effects on tumor control also being dependent on NK cells. However, there are limited studies assessing the role of TIGIT on the function of human NK cells (hNK), particularly in lung cancer. Most studies used NK cell lines or tested TIGIT blockade to reactivate exhausted cells obtained from cancer patients. For therapeutic advancement, a better understanding of TIGIT in the context of activated hNK cells is crucial, which is different than exhausted NK cells, and critical in the context of adoptive NK cell therapeutics that may be combined with TIGIT blockade. In this study, the effect of TIGIT blockade on the anti-tumor activities of human ex vivo-expanded NK cells was evaluated in vitro in the context of lung cancer. TIGIT expression was higher on activated and/or expanded NK cells compared to resting NK cells. More TIGIT+ NK cells expressed major activating receptors and exerted anti-tumor response as compared to TIGIT- cells, indicating that NK cells with greater anti-tumor function express more TIGIT. However, long-term TIGIT engagement upon exposure to PVR+ tumors downregulated the cytotoxic function of expanded NK cells while the inclusion of TIGIT blockade increased cytotoxicity, restored the effector functions against PVR-positive targets, and upregulated immune inflammation-related gene sets. These combined results indicate that TIGIT blockade can preserve the activation state of NK cells during exposure to PVR+ tumors. These results support the notion that a functional NK cell compartment is critical for anti-tumor response and anti-TIGIT/adoptive NK cell combinations have the potential to improve outcomes.

Stigma and mental health problems in an Indian context. Perceptions of people with mental disorders in urban, rural and tribal areas of Kerala.

BACKGROUND: The concept of stigma has been widely used to understand patterns of discrimination and negative ideas surrounding people with mental health problems, yet we know little of the specific nuances of how this might operate beyond the 'Global North'. AIM: This paper aims to explore the notion of stigma in an Indian context by considering the lived experience of patients, carers and community members. METHODS: A sample of 204 participants, representing mental health patients, informal carers and community members was recruited from urban and rural areas in Kerala, India. Participants took part in interviews where they were encouraged to talk about their experiences of mental ill health, attitudes towards these problems, barriers encountered and sources of support. RESULTS: Experiences akin to the experience of stigma in Europe and the United States were elicited but there were important local dimensions specific to the Indian context. The difficulties faced by people with diagnoses of mental disorders in finding marriage partners was seen as an important problem, leading to marriage proposals being refused in some cases, and secrecy on the part of those with mental health problems. Rather than the 'self-stigma' identified in the US, participants were more likely to see this as a collective problem in that it could reflect badly on the family group as a whole rather than just the sufferer. CONCLUSIONS: In the Indian context, the idioms of stigma emphasised impairments in marriage eligibility and the implications for the family group rather than just the self.

Knockout of the inhibitory receptor TIGIT enhances the antitumor response of ex vivo expanded NK cells and prevents fratricide with therapeutic Fc-active TIGIT antibodies.

BACKGROUND: Inhibitory receptor T-cell Immunoreceptor with Ig and ITIM domains (TIGIT) expressed by Natural Killer (NK) and T cells regulates cancer immunity and has been touted as the next frontier in the development of cancer immunotherapeutics. Although early results of anti-TIGIT and its combinations with antiprogrammed death-ligand 1 were highly exciting, results from an interim analysis of phase III trials are disappointing. With mixed results, there is a need to understand the effects of therapeutic anti-TIGIT on the TIGIT+ immune cells to support its clinical use. Most of the TIGIT antibodies in development have an Fc-active domain, which binds to Fc receptors on effector cells. In mouse models, Fc-active anti-TIGIT induced superior immunity, while Fc receptor engagement was required for its efficacy. NK-cell depletion compromised the antitumor immunity of anti-TIGIT indicating the essential role of NK cells in the efficacy of anti-TIGIT. Since NK cells express TIGIT and Fc-receptor CD16, Fc-active anti-TIGIT may deplete NK cells via fratricide, which has not been studied. METHODS: CRISPR-Cas9-based TIGIT knockout (KO) was performed in expanded NK cells. Phenotypic and transcriptomic properties of TIGIT KO and wild-type (WT) NK cells were compared with flow cytometry, CyTOF, and RNA sequencing. The effect of TIGIT KO on NK-cell cytotoxicity was determined by calcein-AM release and live cell imaging-based cytotoxicity assays. The metabolic properties of TIGIT KO and WT NK cells were compared with a Seahorse analyzer. The effect of the Fc-component of anti-TIGIT on NK-cell fratricide was determined by co-culturing WT and TIGIT KO NK cells with Fc-active and Fc-inactive anti-TIGIT. RESULTS: TIGIT KO increased the cytotoxicity of NK cells against multiple cancer cell lines including spheroids. TIGIT KO NK cells upregulated mTOR complex 1 (mTORC1) signaling and had better metabolic fitness with an increased basal glycolytic rate when co-cultured with cancer cells compared with WT NK cells. Importantly, TIGIT KO prevented NK-cell fratricide when combined with Fc-active anti-TIGIT. CONCLUSIONS: TIGIT KO in ex vivo expanded NK cells increased their cytotoxicity and metabolic fitness and prevented NK-cell fratricide when combined with Fc-active anti-TIGIT antibodies. These fratricide-resistant TIGIT KO NK cells have therapeutic potential alone or in combination with Fc-active anti-TIGIT antibodies to enhance their efficacy.

Pre COVID-19 Pandemic Use of Telemedicine for Adherence Promotion in Patients with Psychotic Disorders: A Literature Review.

Introduction: Given the increasing use of telepsychiatry and to serve as a reference point informing future research, our team evaluated the literature on the use of telepsychiatry for medication adherence promotion prior to the COVID-19 pandemic among patients with psychotic disorders. Methods: A search of PubMed, Cochrane, Web of Science, CINAHL, and PsycINFO was conducted using PRISMA guidelines to identify telepsychiatry interventions to enhance medication adherence in patients with primary psychotic disorders. Both quantitative and qualitative data were extracted from the identified articles including study characteristics, interventions, and outcomes. Results: In total, 230 articles were obtained through electronic literature search, and 4 articles were eventually retained that met inclusion criteria. All 4 articles were randomized controlled trials, were adjuncts to in-person usual care, used telephone platforms and targeted medication adherence. Compared to treatment as usual, 3 out of 4 studies found medication adherence was improved and 2 out of 4 studies found improved medication attitudes. Telepsychiatry appeared to be acceptable to patients with psychotic disorders. Discussion: In the pre-Covid-19 literature, telepsychiatry appears promising as an adjunct to usual care for increasing medication adherence among individuals with schizophrenia/schizoaffective disorder. However, given the limited number of papers and exclusive use on telephone-only to deliver telepsychiatry, additional research specific to telepsychiatry for patients with psychosis is needed.

Spontaneous Mediastinal Emphysema.

The author presents a case of spontaneous mediastinal emphysema, also known as the Hamman's syndrome. This case presentation highlights the common features of spontaneous mediastinal emphysema and reminds the clinician to have an index of suspicion for this diagnosis.

Dentine microhardness changes following conventional and alternate irrigation regimens: An in vitro study.

AIM: To compare the changes in microhardness of root dentin caused by two novel irrigation regimens with conventional irrigation. MATERIALS AND METHODS: Forty extracted human permanent incisor teeth were selected. Decoronated roots were separated longitudinally to get 80 specimens that were embedded in autopolymerizing acrylic resin and grounded flat with silicon carbide abrasive papers. Of these, 60 root segments without any cracks or defects were selected and divided into four groups according to the irrigation regimen used (n = 15). Group I: 5% sodium hypochlorite (NaOCl) + 17% ethylenediaminetetraacetic acid (EDTA) + 0.2% chlorhexidine digluconate (CHX) (conventional). Group II: 6% Morinda Citrifolia Juice + 17% EDTA (MCJ). Group III: 5% NaOCl + Q Mix 2 in 1 (QMix). Group IV: Distilled water (control). Irrigation regimens were performed for 5 minutes. Dentin microhardness was measured with a Vickers indenter under a 200-g load and a 20-s dwell time at the midroot level of root dentin. The data were analyzed using Kruskal Wallis test and Dunn's multiple comparison tests. RESULTS: A significant difference was seen in the median values of the four groups. The control group showed the least reduction in microhardness when comparison with the other groups. Except for Group III (Q Mix), the other groups that were tested (MCJ and conventional regimens) showed statistically significant difference from the control group. CONCLUSION: Within the limitation of this study, it was concluded that NaOCl + Q Mix were least detrimental to root dentin microhardness when compared with MCJ and conventional irrigation regimens.