Optimizing Glioblastoma, IDH-wildtype Treatment Outcomes : A Radiomics and Support Vector Machine -Based Approach to Overall Survival Estimation.

Objective: Glioblastoma multiforme (GBM), particularly the IDH-wildtype type, represents a significant clinical challenge due to its aggressive nature and poor prognosis. Despite advancements in medical imaging and its modalities, survival rates have not improved significantly, demanding innovative treatment planning and outcome prediction approaches. Methods: This study utilizes a Support Vector Machine (SVM) classifier using radiomics features to predict the overall survival (OS) of GBM, IDH-wildtype patients to short (< 12 Months) and long (>=12 Months) survivors. A dataset comprising multi-parametric MRI (mpMRI) scans from 574 patients was analyzed. Radiomic features were extracted from T1, T2, FLAIR, and T1-Gd sequences. Low variance features were removed, and Recursive Feature Elimination (RFE) was used to select the most informative features. The SVM model was trained using a k-fold cross-validation approach. Furthermore, clinical parameters such as age, gender, and MGMT promoter methylation status were integrated to enhance prediction accuracy. Results: The model showed reasonable results in terms of cross-validated AUC of 0.84 (95% CI: 0.80-0.90) with (p-value < 0.001) effectively categorizing patients into short and long survivors. Log-rank test (Chi-square statistics) analysis for the developed model was 0.00029 along with the 1.20 Cohen's d effect size. Most importantly, clinical data integration further refined the survival estimates, providing a more fitted prediction that considers individual patient characteristics by Kaplan-Meier curve with p-value<0.0001. Conclusion: The proposed method significantly enhances the predictive accuracy of OS outcomes in GBM, IDH-wildtype patients. By integrating detailed imaging features with key clinical indicators, this model offers a robust tool for personalized treatment planning, potentially improving OS.

Methylome-proteome integration after late-life voluntary exercise training reveals regulation and target information for improved skeletal muscle health.

Exercise is a potent stimulus for combatting skeletal muscle ageing. To study the effects of exercise on muscle in a preclinical setting, we developed a combined endurance-resistance training stimulus for mice called progressive weighted wheel running (PoWeR). PoWeR improves molecular, biochemical, cellular and functional characteristics of skeletal muscle and promotes aspects of partial epigenetic reprogramming when performed late in life (22-24 months of age). In this investigation, we leveraged pan-mammalian DNA methylome arrays and tandem mass-spectrometry proteomics in skeletal muscle to provide detailed information on late-life PoWeR adaptations in female mice relative to age-matched sedentary controls (n = 7-10 per group). Differential CpG methylation at conserved promoter sites was related to transcriptional regulation genes as well as Nr4a3, Hes1 and Hox genes after PoWeR. Using a holistic method of -omics integration called binding and expression target analysis (BETA), methylome changes were associated with upregulated proteins related to global and mitochondrial translation after PoWeR (P = 0.03). Specifically, BETA implicated methylation control of ribosomal, mitoribosomal, and mitochondrial complex I protein abundance after training. DNA methylation may also influence LACTB, MIB1 and UBR4 protein induction with exercise - all are mechanistically linked to muscle health. Computational cistrome analysis predicted several transcription factors including MYC as regulators of the exercise trained methylome-proteome landscape, corroborating prior late-life PoWeR transcriptome data. Correlating the proteome to muscle mass and fatigue resistance revealed positive relationships with VPS13A and NPL levels, respectively. Our findings expose differential epigenetic and proteomic adaptations associated with translational regulation after PoWeR that could influence skeletal muscle mass and function in aged mice. KEY POINTS: Late-life combined endurance-resistance exercise training from 22-24 months of age in mice is shown to improve molecular, biochemical, cellular and in vivo functional characteristics of skeletal muscle and promote aspects of partial epigenetic reprogramming and epigenetic age mitigation. Integration of DNA CpG 36k methylation arrays using conserved sites (which also contain methylation ageing clock sites) with exploratory proteomics in skeletal muscle extends our prior work and reveals coordinated and widespread regulation of ribosomal, translation initiation, mitochondrial ribosomal (mitoribosomal) and complex I proteins after combined voluntary exercise training in a sizeable cohort of female mice (n = 7-10 per group and analysis). Multi-omics integration predicted epigenetic regulation of serine ß-lactamase-like protein (LACTB - linked to tumour resistance in muscle), mind bomb 1 (MIB1 - linked to satellite cell and type 2 fibre maintenance) and ubiquitin protein ligase E3 component N-recognin 4 (UBR4 - linked to muscle protein quality control) after training. Computational cistrome analysis identified MYC as a regulator of the late-life training proteome, in agreement with prior transcriptional analyses. Vacuolar protein sorting 13 homolog A (VPS13A) was positively correlated to muscle mass, and the glycoprotein/glycolipid associated sialylation enzyme N-acetylneuraminate pyruvate lyase (NPL) was associated to in vivo muscle fatigue resistance.

Microbiota succession influences nematode physiology in a beetle microcosm ecosystem.

Unravelling the multifaceted and bidirectional interactions between microbiota and host physiology represents a major scientific challenge. Here, we utilise the nematode model, Pristionchus pacificus, coupled to a laboratory-simulated decay process of its insect host, to mimic natural microbiota succession and investigate associated tripartite interactions. Metagenomics reveal that during initial decay stages, the population of vitamin B-producing bacteria diminishes, potentially due to a preferential selection by nematodes. As decay progresses to nutrient-depleted stages, bacteria with smaller genomes producing less nutrients become more prevalent. Lipid utilisation and dauer formation, representing key nematode survival strategies, are influenced by microbiota changes. Additionally, horizontally acquired cellulases extend the nematodes' reproductive phase due to more efficient foraging. Lastly, the expressions of Pristionchus species-specific genes are more responsive to natural microbiota compared to conserved genes, suggesting their importance in the organisms' adaptation to its ecological niche. In summary, we show the importance of microbial successions and their reciprocal interaction with nematodes for insect decay in semi-artificial ecosystems.

Deep learning assists in acute leukemia detection and cell classification via flow cytometry using the acute leukemia orientation tube.

This study aimed to evaluate the sensitivity of AI in screening acute leukemia and its capability to classify either physiological or pathological cells. Utilizing an acute leukemia orientation tube (ALOT), one of the protocols of Euroflow, flow cytometry efficiently identifies various forms of acute leukemia. However, the analysis of flow cytometry can be time-consuming work. This retrospective study included 241 patients who underwent flow cytometry examination using ALOT between 2017 and 2022. The collected flow cytometry data were used to train an artificial intelligence using deep learning. The trained AI demonstrated a 94.6% sensitivity in detecting acute myeloid leukemia (AML) patients and a 98.2% sensitivity for B-lymphoblastic leukemia (B-ALL) patients. The sensitivities of physiological cells were at least 80%, with variable performance for pathological cells. In conclusion, the AI, trained with ResNet-50 and EverFlow, shows promising results in identifying patients with AML and B-ALL, as well as classifying physiological cells.

Bidirectional association between eating disorder and temporomandibular joint disorder: A retrospective longitudinal nationwide population-based cohort study.

Background/purpose: An increasing body of evidence indicates correlations between the symptoms of temporomandibular disorder and those of eating disorder (ED). However, further investigation is required to elucidate the temporal and causal relationships between the aforementioned disorders. Materials and methods: This retrospective cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Temporomandibular joint disorder (TMJD) was analyzed both as the cause and consequence of ED. We collected the data (from January 1, 1998, to December 31, 2011) of patients with antecedent TMJD (N = 15,059) or ED (N = 1219) and their respective controls (1:10), matched by age, sex, income level, residential location, and comorbidities. This study included patients who had received a new diagnosis of an ED or a TMJD between January 1, 1998, and December 31, 2013. Cox regression models were used to assess the risk of ED or TMJD development in patients with antecedent TMJD or ED. Results: TMJD patients had an approximately 3.70-fold (95 % confidence interval [CI]: 1.93-7.10) risk of ED development. Similarly, patients with ED had an approximately 4.78-fold (95 % CI: 2.52-9.09) risk of TMJD development. Subgroup analyses based on ED subtypes indicated antecedent TMJD and bulimia nervosa as the predictors of increased bulimia nervosa and TMJD risks (hazard ratios: 6.41 [95 % CI: 2.91 to 14.11] and 5.84 [95 % CI: 2.75 to 12.41]), respectively. Conclusion: Previous TMJD and ED are associated with increased risks of subsequent ED and TMJD; these findings suggest the presence of a bidirectional temporal association between TMJD and ED.

Venetoclax Plus Azacitidine as a Bridge Treatment to Allogeneic Stem Cell Transplantation in Unfit Patients with Acute Myeloid Leukemia.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely recommended for unfit patients with newly diagnosed acute myeloid leukemia (AML). Patient survival can improve with venetoclax plus azacitidine (VEN plus AZA). However, the long-term outcome of this treatment strategy is still unsatisfactory. The high response and low treatment toxicity rates of patients receiving VEN plus AZA can provide an opportunity for HSCT among unfit patients. Nevertheless, the outcomes and complications of VEN plus AZA, followed by HSCT, remain unclear. METHODS: This single-center retrospective study aimed to compare patients with newly diagnosed AML receiving VEN plus AZA as induction therapy (n = 27) to those receiving the conventional I3A7 regimen as induction therapy (n = 34). RESULT: The 1-year overall survival, relapse, and non-relapse mortality rates in the two groups were similar. The cytogenetic risks and the hematopoietic cell transplantation-specific comorbidity index are the most significant predictive factors of overall survival. CONCLUSION: In older patients unfit for intensive chemotherapy, a low-intensity regimen with VEN plus AZA is a suitable bridge therapy. Furthermore, allo-HSCT is feasible and can be a curative option.

Did the COVID-19 experience change U.S. parents' attitudes towards HPV vaccination? Results from a national survey.

BACKGROUND: In the U.S., uptake of the HPV vaccine remains below coverage goals. There is concern that negative reactions to emergency initiatives during the COVID-19 pandemic, including vaccination, may have increased some parents' hesitancy towards all vaccines, including HPV. Understanding how different parent populations view routine vaccination post-pandemic is key to strategic efforts to maintaining and increasing uptake of HPV vaccine. METHODS: In early 2022, we recruited an online panel of English-speaking U.S. parents and caregivers, who used the social media platform Twitter and had HPV vaccine-eligible but unvaccinated children age 9-14 years. Respondents completed a 20-minute survey measuring knowledge, attitudes and intentions regarding HPV vaccination for their child, as well as background socio-demographics and health information-seeking practices. Questions regarding experiences during the COVID-19 pandemic included changes in access to preventive care, and perceptions of whether pandemic experiences had positively or negatively affected their attitudes about routine vaccination, with open text capturing reasons for this change. RESULTS: Among 557 respondents, 81 % were definitely or likely to vaccinate their child against HPV, with 12 % being uncertain, and 7 % unlikely to vaccinate. Regarding routine vaccination, most (70 %) felt their attitudes had not changed, while 26 % felt more positively, and only 4 % felt more negatively. Reasons for positive attitude change included increased appreciation for vaccines overall, and motivation to proactively seek preventive care for their child. Negative attitude changes stemmed from distrust of COVID-19 public health efforts including vaccine development, and disillusionment with vaccines' ability to prevent disease. In multivariable models, intention to vaccinate was greater among parents reporting greater education, Democratic affiliation, greater religiosity, and urban residence. Negative attitude change due to the pandemic independently predicted reduced HPV vaccination intention, while positive attitude change predicted positive intention. CONCLUSIONS: Post-pandemic, most U.S. parents remain committed to vaccinating their children against HPV. However, addressing residual COVID-19 concerns could improve uptake among vaccine-hesitant parents.

AI-driven estimation of O6 methylguanine-DNA-methyltransferase (MGMT) promoter methylation in glioblastoma patients: a systematic review with bias analysis.

BACKGROUND: Accurate and non-invasive estimation of MGMT promoter methylation status in glioblastoma (GBM) patients is of paramount clinical importance, as it is a predictive biomarker associated with improved overall survival (OS). In response to the clinical need, recent studies have focused on the development of non-invasive artificial intelligence (AI)-based methods for MGMT estimation. In this systematic review, we not only delve into the technical aspects of these AI-driven MGMT estimation methods but also emphasize their profound clinical implications. Specifically, we explore the potential impact of accurate non-invasive MGMT estimation on GBM patient care and treatment decisions. METHODS: Employing a PRISMA search strategy, we identified 33 relevant studies from reputable databases, including PubMed, ScienceDirect, Google Scholar, and IEEE Explore. These studies were comprehensively assessed using 21 diverse attributes, encompassing factors such as types of imaging modalities, machine learning (ML) methods, and cohort sizes, with clear rationales for attribute scoring. Subsequently, we ranked these studies and established a cutoff value to categorize them into low-bias and high-bias groups. RESULTS: By analyzing the 'cumulative plot of mean score' and the 'frequency plot curve' of the studies, we determined a cutoff value of 6.00. A higher mean score indicated a lower risk of bias, with studies scoring above the cutoff mark categorized as low-bias (73%), while 27% fell into the high-bias category. CONCLUSION: Our findings underscore the immense potential of AI-based machine learning (ML) and deep learning (DL) methods in non-invasively determining MGMT promoter methylation status. Importantly, the clinical significance of these AI-driven advancements lies in their capacity to transform GBM patient care by providing accurate and timely information for treatment decisions. However, the translation of these technical advancements into clinical practice presents challenges, including the need for large multi-institutional cohorts and the integration of diverse data types. Addressing these challenges will be critical in realizing the full potential of AI in improving the reliability and accessibility of MGMT estimation while lowering the risk of bias in clinical decision-making.

People's perception of changes in their abortion attitudes over the life course: A mixed methods approach.

Research examining the extent that people's attitudes toward abortion vary across the life course is mixed. Some studies do not show a strong relationship between abortion attitudes and life stage, while others do find strong associations in both directions-older age associated with both more and less favorable attitudes toward legal abortion. Taken together, these findings suggest that individual attitudes toward abortion are static for some but malleable for others. Little is known about the prevalence, reasons, and directionality of attitude changes. This explanatory sequential mixed methods study investigates people's perceptions of whether, how, why, and for whom their abortion attitudes may have changed over their life course. We qualitatively investigated the reasons (e.g., experiences, life events) that triggered changes in respondents' abortion attitudes and quantitatively explored the sociodemographic factors associated with the perceived direction of those changes. The quantitative data come from a 2020 online survey completed by 1501 English and Spanish-speaking adults in the US. Qualitative data were collected from a subsample (n = 24) of the survey respondents who indicated interest in a follow-up in-depth interview. Our findings indicate that access to information and knowledge played an important role in changing abortion attitudes across a spectrum of support or opposition. For those who indicated becoming more opposed to abortion over time, experiencing parenthood was an important trigger for change and family/religious upbringing were key to shaping attitudes. For those who became more supportive of abortion over time, empathy for women was an important trigger for change and disagreeing with or distancing oneself from family/religious upbringing were key to shaping their attitudes. If attitudinal change occurs, becoming more supportive of abortion over the life-course is more common than becoming more opposed, however there are some nuances across age and gender. Understanding the different factors that influence attitudinal change regarding abortion has important implications for public opinion research and possible ramifications for abortion legality.

Using Surgicel-wrapped Merocel to reduce pain during the removal of nasal packing.

BACKGROUND: Merocel is a commonly used material for nasal packing; nevertheless, the majority of patients experience pain when the nasal packing is removed.Aims/Objectives: This study aims to introduce a novel technique for nasal packing using Surgicel-wrapped Merocel. MATERIAL AND METHODS: Patients who underwent septoplasty received either Merocel or Surgicel-wrapped Merocel as nasal packing. Clinical complications related to bleeding and subjective symptoms associated with the packing materials were assessed. RESULTS: Between 2018 and 2021, a total of thirty-three patients with a deviated nasal septum underwent septoplasty. Among them, eight patients received Merocel nasal packing, while twenty-five patients were treated with the new nasal packing technique involving Surgicel-wrapped Merocel. We observed a significant reduction in pain during removal in the Surgicel-wrapped Merocel group compared to the Merocel group (p = .008). However, no significant differences were noted in other discomforts related to packing or bleeding after removal between these two groups.Conclusions and Significance:Using Surgicel-wrapped Merocel as nasal packing following septoplasty is an effective method to alleviate pain during removal.

The Effects of Aberrant Responding on Model-Fit Assuming Different Underlying Response Processes.

Aberrant responding on tests and surveys has been shown to affect the psychometric properties of scales and the statistical analyses from the use of those scales in cumulative model contexts. This study extends prior research by comparing the effects of four types of aberrant responding on model fit in both cumulative and ideal point model contexts using graded partial credit (GPCM) and generalized graded unfolding (GGUM) models. When fitting models to data, model misfit can be both a function of misspecification and aberrant responding. Results demonstrate how varying levels of aberrant data can severely impact model fit for both cumulative and ideal point data. Specifically, longstring responses have a stronger impact on dimensionality for both ideal point and cumulative data, while random responding tends to have the most negative impact on data model fit according to information criteria (AIC, BIC). The results also indicate that ideal point data models such as GGUM may be able to fit cumulative data as well as the cumulative model itself (GPCM), whereas cumulative data models may not provide sufficient model fit for data simulated using an ideal point model.

Structural Basis for Highly Selective Class II Alpha Phosphoinositide-3-Kinase Inhibition.

Class II phosphoinositide-3-kinases (PI3Ks) play central roles in cell signaling, division, migration, and survival. Despite evidence that all PI3K class II isoforms serve unique cellular functions, the lack of isoform-selective inhibitors severely hampers the systematic investigation of their potential relevance as pharmacological targets. Here, we report the structural evaluation and molecular determinants for selective PI3K-C2α inhibition by a structure-activity relationship study based on a pteridinone scaffold, leading to the discovery of selective PI3K-C2α inhibitors called PITCOINs. Cocrystal structures and docking experiments supported the rationalization of the structural determinants essential for inhibitor activity and high selectivity. Profiling of PITCOINs in a panel of more than 118 diverse kinases showed no off-target kinase inhibition. Notably, by addressing a selectivity pocket, PITCOIN4 showed nanomolar inhibition of PI3K-C2α and >100-fold selectivity in a general kinase panel. Our study paves the way for the development of novel therapies for diseases related to PI3K-C2α function.

People's knowledge of and attitudes toward abortion laws before and after the Dobbs v. Jackson decision.

Although media response to the Dobbs v. Jackson Women's Health Organization decision was widespread in the United States, the extent to which people were aware of the Mississippi law leading to the decision, the Dobbs v. Jackson case, is unclear, as are the resulting effects of the decision on legal abortion. As such, we examined people's awareness of abortion legality prior to and after the Dobbs v. Jackson decision announcement, as well as the potential implications associated with the decision (i.e. overturning of Roe v. Wade). We also examined people's attitudes toward abortion legality, specifically focusing on 15 weeks' gestation to correspond with the Mississippi law that led to Dobbs v. Jackson. Data were collected across two studies at different times. In Study 1, a 15-minute survey was administered to IPSOS' KnowledgePanel (N = 1014) prior to the decision announcement. A shorter version of that survey was administered to a second sample using NORC's AmeriSpeak Omnibus panel (N = 1002). Nearly half of that sample (42.2%) completed the survey prior to the decision announcement. People were generally unaware of the Mississippi law, the Dobbs v. Jackson case, and implications associated with the decision (e.g. overturning Roe v. Wade). People generally endorsed abortion being legal at 15 weeks or later, but this varied by circumstance. We did not find meaningful effects of the decision announcement on people's knowledge and attitudes. Our findings suggest that the intense response to the decision from the media and people involved in the abortion movement may not represent the general public's reaction.

Same-Day Bilateral Intravitreal Dexamethasone Implants for the Treatment of Diabetic Macular Edema.

INTRODUCTION: The aim of this study was to evaluate the outcomes and complications associated with the use of same-day bilateral intravitreal dexamethasone (DEX) implants for the treatment of diabetic macular edema (DME). METHODS: This retrospective analysis of an open-label, multicenter, consecutive case series included 130 eyes of 65 patients with bilateral DME who were treated with intravitreal DEX implants. The patients were divided into two groups: a control group (comprising 40 eyes treated with an alternating unilateral regimen) and a study group (comprising 90 eyes treated with concomitant bilateral DEX implants). All patients were followed up monthly after implantation. The changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to sixth month after implantation, and ocular adverse effects such as intraocular pressure, cataract, and tolerability of bilateral implantation were reviewed. The primary endpoint was to assess the safety of the same-day bilateral treatment protocol. The secondary endpoints focused on evaluating the functional and anatomical changes associated with bilateral simultaneous or alternating implantations. RESULTS: At 6 months after implantation, mean BCVA increased and CRT decreased in both groups. Moreover, no serious ocular adverse effects were observed. In addition, no differences were observed between the two groups in the number of patients who required extra follow-up visits or the number of extra visits made in addition to the treatment schedule. CONCLUSIONS: Same-day bilateral intravitreal DEX implants are associated with a low complication rate and are well tolerated by patients. This safe practice may optimize efficiency and reduce the burden on both the health-care system and patients, when used to treat bilateral DME.

Perceptions of abortion access across the United States prior to the Dobbs v. Jackson Women's Health Organization decision: Results from a national survey.

CONTEXT: Abortion is common in the United States (US), although access is becoming more difficult for some. In addition to restrictive policies that ban most abortion, limit the number of providers and increase costs, barriers to access also include less supportive cultural climates and stigma related to abortion. Prior to the Dobbs v. Jackson Women's Health decision of the United States Supreme Court, research suggested that people generally believed it was easy to access abortion, but this research did not examine the underlying factors that drive these perceptions. METHODS: In 2019, using data from closed and open-ended survey questions, we examined differences in people's assessment of abortion access within the state they reside and factors that influence those perceptions. We recruited English- and Spanish-speaking US adults (N = 2599) from Qualtrics' national panel using quota-based sampling to participate in a web-based survey. We used multinomial logistic regression to examine predictors of access perceptions across demographic characteristics and thematic analysis to analyze open-ended responses. RESULTS: Fifty-three percent of participants believed abortion was easy to access in their state. Spanish speakers and participants from legislatively "hostile" states were more likely to perceive access as difficult. Legality-related knowledge and pro-life identity were associated with perceiving abortion access as easy. CONCLUSIONS: Prior to Dobbs, participants' interpretation of the ease or difficulty of accessing abortion were subjective. Misconceptions about state abortion laws and the prevalence of providers were common, suggesting a need for more education about abortion laws, policies, and access.

Boron Neutron Capture Therapy Followed by Image-Guided Intensity-Modulated Radiotherapy for Locally Recurrent Head and Neck Cancer: A Prospective Phase I/II Trial.

BACKGROUND: This trial investigated the efficacy and safety of salvage boron neutron capture therapy (BNCT) combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for recurrent head and neck cancer after prior radiotherapy (RT). METHODS: BNCT was administered using an intravenous boronophenylalanine-fructose complex (500 mg/kg) in a single fraction; multifractionated IG-IMRT was administered 28 days after BNCT. For BNCT, the mucosa served as the dose-limiting organ. For IG-IMRT, the clinical target volume (CTV) and the planning target volume (PTV) were generated according to the post-BNCT gross tumor volume (GTV) with chosen margins. RESULTS: This trial enrolled 14 patients, and 12 patients received combined treatment. The median BNCT average dose for the GTV was 21.6 Gy-Eq, and the median IG-IMRT dose for the PTV was 46.8 Gy/26 fractions. After a median (range) follow-up period of 11.8 (3.6 to 53.2) months, five patients had a complete response and four had a partial response. One patient had grade 4 laryngeal edema; another patient had a grade 4 hemorrhage. Most tumor progression occurred within or adjacent to the CTV. The 1-year overall survival and local progression-free survival rates were 56% and 21%, respectively. CONCLUSION: Despite the high response rate (64%) of this trial, there was a high incidence of in-field and marginal failure with this approach. Future studies combining BNCT with modalities other than radiation may be tried.

Bidirectional Associations of Temporomandibular Joint Disorders with Major Depressive and Anxiety Disorders.

OBJECTIVES: Mounting evidence indicates the associations of temporomandibular disorders (TMD) with depression and anxiety symptoms. However, the temporal and casual relationships between TMD and depression and between TMD and anxiety must be further clarified. METHODS: This study is a retrospective cohort analysis that employed data from the Taiwan National Health Insurance Database and comprised the following sub analyses: temporomandibular joint disorders (TMJD) as the cause of subsequent major depressive disorder (MDD) or anxiety disorders (AnxDs) and TMJD as the consequence of MDD or AnxDs. Patients with antecedent TMJD (N = 12,152 for the MDD study and 11,023 for the AnxD study), MDD (N = 28,743), or AnxDs (N = 21,071) and their respective control cohorts were identified between January 1, 1998 and December 31, 2011. The control cohorts (1:10) were matched by age, sex, income, residential location, and comorbidities. Individuals with subsequent new-onset TMJD, MDD, or AnxDs were identified from January 1, 1998 to December 31, 2013. The risk of the outcome disorders of the individuals with antecedent TMJD, MDD, or AnxD were estimated using Cox regression models. RESULTS: Patients with TMJD had an approximately 3-fold higher risk (hazard ratio [HR]: 3.98, 95% confidence interval [CI]: 3.28-4.84) of subsequent MDD development and a 7-fold higher risk (HR: 7.26, 95% CI: 5.90-8.94) of AnxD development than those without TMJD. Antecedent MDD and AnxDs were predictive of 5.80-fold (95% CI: 4.81-6.98) and 8.29-fold (95% CI: 6.67-10.30), respectively, increases in the risk of subsequent TMJD development. CONCLUSIONS: Our results demonstrate that precedent TMJD and MDD/AnxDs are associated with elevated risks of subsequent MDD/AnxDs and TMJD developments and indicate temporal associations of TMJD with MDD and AnxDs are bidirectional.

Clinical Spectrum and Trajectory of Innovative Therapeutic Interventions for Insomnia: A Perspective.

Increasing incidences of insomnia in adults, as well as the aging population, have been reported for their negative impact on the quality of life. Insomnia episodes may be associated with neurocognitive, musculoskeletal, cardiovascular, gastrointestinal, renal, hepatic, and metabolic disorders. Epidemiological evidence also revealed the association of insomnia with oncologic and asthmatic complications, which has been indicated as bidirectional. Two therapeutic approaches including cognitive behavioral therapy (CBT) and drugs-based therapies are being practiced for a long time. However, the adverse events associated with drugs limit their wide and long-term application. Further, Traditional Chinese medicine, acupressure, and pulsed magnetic field therapy may also provide therapeutic relief. Notably, the recently introduced cryotherapy has been demonstrated as a potential candidate for insomnia which could reduce pain, by suppressing oxidative stress and inflammation. It seems that the synergistic therapeutic approach of cryotherapy and the above-mentioned approaches might offer promising prospects to further improve efficacy and safety. Considering these facts, this perspective presents a comprehensive summary of recent advances in pathological aetiologies of insomnia including COVID-19, and its therapeutic management with a greater emphasis on cryotherapy.

Acute Necrotizing Retinopathy After Xen Gel Stent Implantation.

PRCIS: We report a case of a 45-year-old woman who developed serous retinal detachment, hypotony, and retinal necrosis after Xen gel stent implantation. ABSTRACT: A 45-year-old woman developed sudden blurring of vision 4 days after Xen gel stent replacement surgery. Persistent hypotony, uveitis, and serious retinal detachment rapidly progressed despite medical and surgical treatments. Retinal necrosis, optic atrophy, and total blindness developed within 2 months. Although infectious and autoimmune-related uveitis were ruled out through negative culture and blood test results, acute postoperative infectious endophthalmitis could not be completely excluded in this case. However, toxic retinopathy related to mitomycin- C was suspected eventually.