Centripetal endoscopic sinus surgery in rhinogenic headache.

OBJECTIVES: The aim of this manuscript is to analyse a diagnostic protocol to select correctly patients with Rhinogenic Headache Contact Point (RH) and to investigate the effect of surgical treatment and medical therapy in pain relief. METHODS: A prospective no-randomized study selected adult patients with headache and nasal alteration at CT exam or endoscopic vision with positive response to test with nasal spray with corticosteroids and antihistamine or/and local anesthesia test to the contact points. MIDAS score, intensity score, daily duration of symptoms, frequency of headache in the last month were collected in patients who performed surgery and in patients who performed medical therapy. RESULTS: Following the inclusion, 415 patients were selected for this study. 302 patients performed nasal surgery (septoplasty, turbinoplasty and/or endoscopic surgery with centripetal technique), 113 performed medical therapy. There was a statistically significant improvement in MIDAS score, intensity score, daily duration of symptoms, frequency of headache in the last month in patients who performed surgery and in patients who performed medical therapy. Regarding the comparison between patients who performed surgery (Group A) and patients who performed only medical therapy for RH (Group B), better outcomes were obtained by Group A. Considering the daily life handicap index, the lowest handicap was obtained in Group A. CONCLUSION: This study demonstrates that surgery, using in some cases centripetal technique, gives an improvement statistically significant than medical therapy in RH. The use of nasal spray with corticosteroids and with anti-histamine is a good method in the diagnosis of RH, especially in patients with anatomical variants such as concha bullosa, agger nasi cells and Haller cells.

Impact of Erenumab on Migraine Disability: A Three-Month MIDAS (Migraine Disability Assessment Scale) Score Analysis at Dubai Health Facilities.

BACKGROUND AND AIM: Migraine is a prevalent neurological disorder causing recurrent headaches that significantly impact daily life. Erenumab, a calcitonin gene-related peptide (CGRP) receptor antagonist, has emerged as a promising treatment for migraine. CGRP is thought to play a role in migraine pathophysiology, and erenumab works by blocking CGRP binding to its receptors. Erenumab has been found to be effective in reducing migraine frequency, with potential benefits for improving patient outcomes. This study investigated the impact of erenumab on migraine disability in patients treated at Dubai Health facilities. We specifically assessed changes in Migraine Disability Assessment Scale (MIDAS) scores before and after a three-month treatment period. METHODS: This retrospective analysis examined data from 26 patients diagnosed with migraine according to the established criteria. All patients received erenumab treatment for three months. MIDAS, a validated tool, was used to quantify migraine-related disability at baseline and after treatment completion. Due to potential skewness in the data distribution, the statistical analysis focused on the median change in MIDAS scores across groups based on gender and erenumab dosage. Non-parametric tests were employed to assess group differences. RESULTS: Erenumab treatment resulted in a median decrease of 13 points in MIDAS scores, suggesting a potential improvement in migraine disability at three months. Statistical analysis revealed no statistically significant group differences regarding MIDAS score changes between genders or erenumab dosage groups. However, trends toward improvement were observed in all subgroups. CONCLUSION: While not statistically significant due to the limited sample size and the absence of a control group, these findings suggest a potential benefit of erenumab in reducing migraine disability. Future research with more extensive, controlled trials is warranted to definitively assess erenumab's effectiveness and explore potential treatment regimen variations for optimal patient outcomes.

Unlocking mitochondrial dysfunction-associated senescence (MiDAS) with NAD+ - A Boolean model of mitochondrial dynamics and cell cycle control.

The steady accumulation of senescent cells with aging creates tissue environments that aid cancer evolution. Aging cell states are highly heterogeneous. 'Deep senescent' cells rely on healthy mitochondria to fuel a strong proinflammatory secretome, including cytokines, growth and transforming signals. Yet, the physiological triggers of senescence such as reactive oxygen species (ROS) can also trigger mitochondrial dysfunction, and sufficient energy deficit to alter their secretome and cause chronic oxidative stress - a state termed Mitochondrial Dysfunction-Associated Senescence (MiDAS). Here, we offer a mechanistic hypothesis for the molecular processes leading to MiDAS, along with testable predictions. To do this we have built a Boolean regulatory network model that qualitatively captures key aspects of mitochondrial dynamics during cell cycle progression (hyper-fusion at the G1/S boundary, fission in mitosis), apoptosis (fission and dysfunction) and glucose starvation (reversible hyper-fusion), as well as MiDAS in response to SIRT3 knockdown or oxidative stress. Our model reaffirms the protective role of NAD+ and external pyruvate. We offer testable predictions about the growth factor- and glucose-dependence of MiDAS and its reversibility at different stages of reactive oxygen species (ROS)-induced senescence. Our model provides mechanistic insights into the distinct stages of DNA-damage induced senescence, the relationship between senescence and epithelial-to-mesenchymal transition in cancer and offers a foundation for building multiscale models of tissue aging.

Differences in hypersensitivity reactions and gadolinium deposition disease/symptoms associated with gadolinium exposure to gadolinium-based contrast agents: new insights based on global databases VigiBase, FAERS, and IQVIA-MIDAS.

BACKGROUND: Hypersensitivity reactions (HSRs) can occur unexpectedly and be life-threatening when gadolinium-based contrast agents (GBCAs) are used. Gadolinium deposition disease (GDD) and symptoms associated with gadolinium exposure (SAGE) have been controversial for a long time. However, similar studies are currently incomplete or outdated. Therefore, comparing the safety of different GBCAs in terms of HSRs and GDD/SAGE using the latest post-marketing safety data should yield further insights into safely using GBCAs. METHODS: The safety differences between all GBCAs to GDD and the spectrum of GBCA-related HSRs were all compared and analyzed by using the World Health Organization database VigiBase and the FDA Adverse Event Reporting System (FAERS) database in this study. A further analysis of SAGE was also conducted using FAERS data. The lower limit of the reporting odds ratio (ROR) 95% confidence interval was used for signal detection. Moreover, the frequency of HSRs was calculated by dividing the number of reports in VigiBase by the total sales volume (measured in millions) from 2008 to 2022 in the IQVIA Multinational Integrated Data Analysis System. All adverse events were standardized using the Medical Dictionary for Drug Regulatory Activities (MedDRA) 26.0. RESULTS: This study shows that all GBCAs have the potential to induce HSRs, with nonionic linear GBCAs exhibiting a comparatively lower signal. According to standardized MedDRA query stratification analysis, gadobutrol had a greater ROR025 for angioedema. The ROR025 of gadobenate dimeglumine and gadoteridol is larger for anaphylactic/anaphylactoid shock conditions. Regarding severe cutaneous adverse reactions, only gadoversetamide and gadodiamide showed signals in FAERS and VigiBase. There were also differences in the frequency of HSRs between regions. Regarding GDD, gadoterate meglumine, and gadoteridol had a lower ROR025. An analysis of the 29 preferred terms linked to SAGE indicated that special consideration should be given to the risk of skin induration associated with gadoversetamide, gadopentetate dimeglumine, gadobenate dimeglumine, gadodiamide, and gadoteridol. Additionally, gadodiamide and gadoteridol pose a greater risk of skin tightness compared to other GBCAs. CONCLUSIONS: The risk differences among GBCAs using data from several sources were compared in this study. However, as a hypothesis-generating method, a clear causal relationship would require further research and validation.

TDP1 phosphorylation by CDK1 in mitosis promotes MUS81-dependent repair of trapped Top1-DNA covalent complexes.

Topoisomerase 1 (Top1) controls DNA topology, relieves DNA supercoiling during replication and transcription, and is critical for mitotic progression to the G1 phase. Tyrosyl-DNA phosphodiesterase 1 (TDP1) mediates the removal of trapped Top1-DNA covalent complexes (Top1cc). Here, we identify CDK1-dependent phosphorylation of TDP1 at residue S61 during mitosis. A TDP1 variant defective for S61 phosphorylation (TDP1-S61A) is trapped on the mitotic chromosomes, triggering DNA damage and mitotic defects. Moreover, we show that Top1cc repair in mitosis occurs via a MUS81-dependent DNA repair mechanism. Replication stress induced by camptothecin or aphidicolin leads to TDP1-S61A enrichment at common fragile sites, which over-stimulates MUS81-dependent chromatid breaks, anaphase bridges, and micronuclei, ultimately culminating in the formation of 53BP1 nuclear bodies during G1 phase. Our findings provide new insights into the cell cycle-dependent regulation of TDP1 dynamics for the repair of trapped Top1-DNA covalent complexes during mitosis that prevents genomic instability following replication stress.

A Study of the Effect of Treatment On the Clinical Profile, Pain, and Disability in Migraine Patients Seen in a Tertiary Hospital.

Background: Migraine is a disabling disease that poses a significant societal burden. Migraine is a major cause of disability. Migraine is the eighth leading disease-causing disability in the population. Objective: To study the clinical profile and measure the pain and migraine-related disability of patients with all types of migraine using the McGill pain assessment scale and Migraine Disability Assessment (MIDAS) before and after 3 months of effect on the medication. Methods: A Prospective-Cross sectional study was carried out in a multispecialty hospital with male and female patients between 18 and 65 years. The data were collected from the patients directly through the questionnaire of McGill pain assessment scale-short form (SF) and MIDAS, which was provided before and after the medication. Results: There were 165 subjects of which 52 were men and 113 were women. The mean age of all the subjects was 43 years. About 26.06% of the subjects had a family history of headaches. The scores of McGill pain and MIDAS assessment before and after medication were as follows: 0-15 were 30.90% and 73.33%, Score 16-30 were 54.54% and 18.18%, the score of 31-45 were 14.54% and 7.87% of the subjects. MIDAS grade I was 17.57% and 50.90%, Grade II 33.93% and 21.81%, Grade III 30.30% and 15.75% Grade IV 18.18% and 11.51% of the subjects. Discussion: The calculated "t" value between the before and after medication values of McGill and MIDAS by paired 't-test was 13.85 and 17.49 respectively. As the calculated "t" value is more than the table value, the alternate hypothesis is accepted. Conclusion: This study confirms that there is a significant difference in disability levels before and after acute and preventative treatments when measured over 3 months. In addition, the preponderance of females was high, and the functional disability that affects work and social activity associated with migraine is moderate to severe.

Effectiveness of galcanezumab on sleep quality, migraine outcome, and multidimensional patient-reported outcome measures: a real-world experience in Turkish patients with episodic and chronic migraine.

Introduction: This real-world study aimed to investigate the impact of galcanezumab on sleep quality, migraine outcome and multidimensional patient-reported outcomes measures (PROMs) in patients with episodic migraine (EM) and chronic migraine (CM). Methods: Fifty-four patients with episodic migraine (n = 24) or chronic migraine (n = 30) received a 3-month series of galcanezumab injections and were evaluated for sleep quality, measured using the Pittsburgh Sleep Quality Index (PSQI), as well as migraine outcomes such as monthly headache days (MHDs), monthly migraine days (MMDs), and headache severity. Patient-reported outcome measures (PROMs) such as the Migraine Disability Assessment Scale (MIDAS), Headache Impact Test-6 (HIT-6), SF-36 Health-related Quality of Life (HRQoL), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) were additionally included in the assessment. Results: The percentage of patients with poor sleep quality (total PSQI scores ≥ 5) was 72.7% at baseline, decreasing to 57.5% and 56.2% at the 1st and 2nd months, respectively. By the 3rd month of galcanezumab injections, significant improvement was observed in the sleep disturbances domain in the overall study population (p = 0.016), and in subgroups of patients with low anxiety levels (p = 0.016) and none/minimal depression (p = 0.035) at baseline. Patients with sleep disorder at baseline exhibited marked improvements in total PSQI scores (p = 0.027) and in the subjective sleep quality (p = 0.034) and daytime dysfunction (p = 0.013) domains, by the 3rd month. Over the 1st, 2nd, and 3rd months, there were significant improvements in MHDs (p < 0.001), MMDs (p < 0.001), HIT-6 scores (p < 0.001 for each), BAI scores (p < 0.001 for each), BDI scores (p ranged from 0.048 to <0.001), and HRQoL scores (p ranged from 0.012 to <0.001). Conclusion: Galcanezumab demonstrates notable benefits in improving sleep quality, along with a comorbidity-based and domain-specific effect on sleep parameters, which involved sleep disturbances domain in patients without depression or anxiety at baseline but the total PSQI scores, subjective sleep quality and daytime dysfunction in those with sleep disorder at baseline. The treatment also facilitates rapid-onset enhancements in migraine outcomes as well as various PROMs.

The Assessment of Clinical Characteristics, Treatment Patterns, and Burden of Illness in Patients With Episodic and Chronic Migraine: A Cross-Sectional Study.

INTRODUCTION: Migraine is a prevalent and disabling primary headache disorder worldwide, causing significant years lost due to disability (YLD) and impacting various aspects of everyday life. Despite its high prevalence and substantial burden, there is a lack of comprehensive data on clinical patterns and management trends, in places like Tamil Nadu, India. This study aims and also fill gaps by investigating and analyzing the clinical characteristics, treatment patterns, and illness burden among patients with episodic migraine (EM) and chronic migraine (CM) in the state of Tamil Nadu. STUDY: This cross-sectional retrospective study was conducted at the Department of Neurology, Madras Medical College, Chennai, over a three-month period starting from January 2024 to March 2024. The study included migraine patients aged 18 years and above who met the International Classification of Headache Disorders (ICHD)-3 criteria and took treatment at the department. Data were collected using patient interviews, medical records, and counseling sessions and using a pre-designed questionnaire. Patient demographics, clinical characteristics, symptom prevalence, prescription patterns, and illness burden were analyzed accordingly. The Migraine Disability Assessment (MIDAS) questionnaire was used to measure the burden of illness. RESULTS: The analysis involved 400 migraine patients, 92.5% of them having EM and 7.5% of them having CM. The mean age of patients was 37.5 years, with a predominance of females (73.5%). Patients with CM had having significantly higher average number of headache days per month when compared to those with EM. Tension-type headache (TTH) and medication-overuse headache (MOH) were more prevalent in those CM patients. Trigger factors include lack of sleep, bright light exposure, and stress. Comorbidities such as diabetes mellitus, obesity, and depression were significantly higher in CM patients. Acute treatment included NSAIDs and Triptans, while preventive therapy was more commonly used in CM patients. The mean MIDAS score was significantly higher in CM patients, which indicates greater disability. CONCLUSION: The study provides valuable insights into the clinical characteristics, treatment patterns, and burden of illness among migraine patients in Tamil Nadu, India. Significant differences were observed between EM and CM patients, which highlights the need for comprehensive management strategies. Preventive therapy, lifestyle modifications, and comprehensive assessment of disability are all important in addressing the variable needs of migraine patients and also reducing the burden of illness. Further research is necessary to explore additional factors influencing migraine outcomes in this population.

Effects of Gluten on Gut Microbiota in Patients with Gastrointestinal Disorders, Migraine, and Dermatitis.

As gluten may trigger gastrointestinal disorders (GIDs), its presence or absence in the diet can change the diversity and proportion of gut microbiota. The effects of gluten after six weeks of a double-blind, placebo-controlled intervention with a gluten-free diet (GFD) were studied in participants with GIDs suffering from migraines and atopic dermatitis (n = 46). Clinical biomarkers, digestive symptoms, stool, the Migraine Disability Assessment questionnaire, and zonulin levels were analyzed. Next-generation sequencing was used to amplify the 16S rRNA gene of bacteria and the internal transcribed spacer (ITS) regions of fungi. The GFD increased Chao1 fungal diversity after the intervention, while the fungal composition showed no changes. Bacterial diversity and composition remained stable, but a positive association between bacterial and fungal Chao1 diversity and a negative association between Dothideomycetes and Akkermansia were observed. GIDs decreased in both groups and migraines improved in the placebo group. Our findings may aid the development of GID treatment strategies.

RAD52-dependent mitotic DNA synthesis is required for genome stability in Cyclin E1-overexpressing cells.

Overexpression of Cyclin E1 perturbs DNA replication, resulting in DNA lesions and genomic instability. Consequently, Cyclin E1-overexpressing cancer cells increasingly rely on DNA repair, including RAD52-mediated break-induced replication during interphase. We show that not all DNA lesions induced by Cyclin E1 overexpression are resolved during interphase. While DNA lesions upon Cyclin E1 overexpression are induced in S phase, a significant fraction of these lesions is transmitted into mitosis. Cyclin E1 overexpression triggers mitotic DNA synthesis (MiDAS) in a RAD52-dependent fashion. Chemical or genetic inactivation of MiDAS enhances mitotic aberrations and persistent DNA damage. Mitosis-specific degradation of RAD52 prevents Cyclin E1-induced MiDAS and reduces the viability of Cyclin E1-overexpressing cells, underscoring the relevance of RAD52 during mitosis to maintain genomic integrity. Finally, analysis of breast cancer samples reveals a positive correlation between Cyclin E1 amplification and RAD52 expression. These findings demonstrate the importance of suppressing mitotic defects in Cyclin E1-overexpressing cells through RAD52.

Magilock: a reliable control triggering method in multi-channel eye-control systems.

Eye-tracking technology brings a different human-computer interaction experience to users because of its intuitive, natural, and hands-free operation characteristics. Avoiding the Midas touch problem and improving the accuracy of interaction are among the main goals of the research and development of eye-control systems. This study reviews the methods and limitations of research on avoiding the Midas touch problem. For typical control clicking operations with low fault tolerance, such as mode switching and state selection in an eye-control system, this study proposes Magilock, a more reliable control triggering method with a high success rate in multi-channel eye-control systems. Magilock adds a control pre-locked mechanism between the two interactive steps of eye-control channel positioning control and other interactive channel triggering controls in the multi-channel eye-control system. This effectively avoids incorrect control triggering caused by multi-channel coordination disorder and gaze-point drift. This study also conducted ergonomic experiments to explore the lock and unlock times of the control pre-locked mechanism in Magilock. Taking into account the experimental data and subjective evaluation of the participants, we recommend setting the lock time and the unlock time of Magilock to 200 ms.

Premonitory symptoms in migraine: A REFORM Study.

BACKGROUND: Estimates of proportions of people with migraine who report premonitory symptoms vary greatly among previous studies. Our aims were to establish the proportion of patients reporting premonitory symptoms and its dependency on the enquiry method. Additionally, we investigated the impact of premonitory symptoms on disease burden using Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS) and World Health Organization Disability Assessment 2.0 (WHODAS 2.0), whilst investigating how various clinical factors influenced the likelihood of reporting premonitory symptoms. METHODS: In a cross-sectional study, premonitory symptoms were assessed among 632 patients with migraine. Unprompted enquiry was used first, followed by a list of 17 items (prompted). Additionally, we obtained clinical characteristics through a semi-structured interview. RESULTS: Prompted enquiry resulted in a greater proportion reporting premonitory symptoms than unprompted (69.9% vs. 43.0%; p < 0.001) and with higher symptom counts (medians 2, interquartile range = 0-6 vs. 1, interquartile range = 0-1; p < 0.001). The number of symptoms correlated weakly with HIT-6 (ρ = 0.14; p < 0.001) and WHODAS scores (ρ = 0.09; p = 0.041). Reporting postdromal symptoms or triggers increased the probability of reporting premonitory symptoms, whereas monthly migraine days decreased it. CONCLUSIONS: The use of a standardized and optimized method for assessing premonitory symptoms is necessary to estimate their prevalence and to understand whether and how they contribute to disease burden.

The cell cycle revisited: DNA replication past S phase preserves genome integrity.

Accurate and complete DNA duplication is critical for maintaining genome integrity. Multiple mechanisms regulate when and where DNA replication takes place, to ensure that the entire genome is duplicated once and only once per cell cycle. Although the bulk of the genome is copied during the S phase of the cell cycle, increasing evidence suggests that parts of the genome are replicated in G2 or mitosis, in a last attempt to secure that daughter cells inherit an accurate copy of parental DNA. Remaining unreplicated gaps may be passed down to progeny and replicated in the next G1 or S phase. These findings challenge the long-established view that genome duplication occurs strictly during the S phase, bridging DNA replication to DNA repair and providing novel therapeutic strategies for cancer treatment.

Nascent DNA sequencing and its diverse applications in genome integrity research.

Multiple DNA repair pathways and biological responses to DNA damage have evolved to protect cells from various types of lesions to which they are subjected. Although DNA repair systems are mechanistically distinct, all process the damaged region and then insert new bases to fill the gap. In 1969, Robert Painter developed an assay called "unscheduled" DNA synthesis (UDS), which measures DNA repair synthesis as the uptake of radiolabeled DNA precursors distinct from replicative synthesis. Contemporary detection of nascent DNA during repair by next-generation sequencing grants genome-wide information about the nature of lesions that threaten genome integrity. Recently, we developed the SAR-seq (synthesis associated with repair sequencing) method, which provides a high-resolution view of UDS. SAR-seq has been utilized to map programmed DNA repair sites in non-dividing neurons, replication initiation zones, monitor 53BP1 function in countering end-resection, and to identify regions of the genome that fail to complete replication during S phase but utilize repair synthesis during mitosis (MiDAS). As an example of SAR-seq, we present data showing that sites replicated during mitosis correspond to common fragile sites, which have been linked to tumor progression, cellular senescence, and aging.

Monitoring of optic sheath diameter during acute migraine attack: an objective criteria for the severity of disease.

BACKGROUND: The etiology of migraine can be complex and multifactorial but not clear, also, intracranial pressure has been already associated with migraine attacks. This study aimed to monitor intracranial pressure during migraine attack to understand the possible relations with disease and severity. METHODS: A prospective randomized study was designed. Patients with a definitive diagnosis of migraine underwent ultrasonography for optic nerve sheath diameter (ONSD) measurement before treatment and were re-measured after the attack was resolved. The severity of the migraine was assessed with Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment (MIDAS) questionnaire before the treatment and after the symptoms regressed. ONSD values and scores from the questionnaires were compared before and after the migraine attack. RESULTS: The study included 11 (52.4%) women and 10 (47.6%) men, and 42 eyes were evaluated. ONSD was detected as 4.23 ± 0.26 mm in the right eye and 4.10 ± 0.32 mm in the left eye during the migraine attack and decreased to 3.65 ± 0.41 mm in the right eye and 3.50 ± 0.33 mm in the left eye after the attack was treated (p < 0.001, both). A similar statistical improvement was found in HIT-6 and MIDAS scores with ONSD after treatment (p < 0.001). A significant positive correlation was found between the ONSD value in both eyes and HIT-6/MIDAS scores during the migraine attack, and also, after the migraine attack. CONCLUSION: A subjective increase of ONSD values during the migraine attack decreased after the disease resolved, also changes in ONSD values were significantly correlated with the severity of symptoms.

Effect of repetition of vertical and horizontal routes on navigation performance in Australian bull ants.

Solitarily foraging ant species differ in their reliance on their two primary navigational systems- path integration and visual learning. Despite many species of Australian bull ants spending most of their foraging time on their foraging tree, little is known about the use of these systems while climbing. "Rewinding" displacements are commonly used to understand navigational system usage, and work by introducing a mismatch between these navigational systems, by displacing foragers after they have run-down their path integration vector. We used rewinding to test the role of path integration on the arboreal and terrestrial navigation of M. midas. We rewound foragers along either the vertical portion, the ground surface portion, or across both portions of their homing trip. Since rewinding involves repeatedly capturing and releasing foragers, we included a nondisplacement, capture-and-release control, in which the path integration vector is unchanged. We found that rewound foragers do not seem to accumulate path integration vector, although a limited effect of vertical rewinding was found, suggesting a potential higher sensitivity while descending the foraging tree. However, the decrease in navigational efficiency due to capture was larger than the vertical rewinding effect, which along with the negative impact of the vertical surface, and an interaction between capture and rewinding, may suggest aversion rather than path integration caused the vertical rewinding response. Together these results add to the evidence that M. midas makes minimal use of path integration while foraging, and the growing evidence that they are capable of quickly learning from aversive stimulus.

FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination.

Ubiquitination of proliferating cell nuclear antigen (PCNA) at lysine 164 (K164) activates DNA damage tolerance pathways. Currently, we lack a comprehensive understanding of how PCNA K164 ubiquitination promotes genome stability. To evaluate this, we generated stable cell lines expressing PCNAK164R from the endogenous PCNA locus. Our data reveal that the inability to ubiquitinate K164 causes perturbations in global DNA replication. Persistent replication stress generates under-replicated regions and is exacerbated by the DNA polymerase inhibitor aphidicolin. We show that these phenotypes are due, in part, to impaired Fanconi anemia group D2 protein (FANCD2)-dependent mitotic DNA synthesis (MiDAS) in PCNAK164R cells. FANCD2 mono-ubiquitination is significantly reduced in PCNAK164R mutants, leading to reduced chromatin association and foci formation, both prerequisites for FANCD2-dependent MiDAS. Furthermore, K164 ubiquitination coordinates direct PCNA/FANCD2 colocalization in mitotic nuclei. Here, we show that PCNA K164 ubiquitination maintains human genome stability by promoting FANCD2-dependent MiDAS to prevent the accumulation of under-replicated DNA.

Evaluating the effectiveness of the Ministry of Health restriction policy on seasonal antibiotic consumption trends in Saudi Arabia, 2016-2020.

Background: Understanding antibiotic consumption patterns over time is essential to optimize prescribing practices and minimizing antimicrobial resistance. This study aimed to determine whether the antibiotics restriction policy launched by the Saudi Ministry of Health in April 2018 has impacted antibiotic use by assessing changes and seasonal variations following policy enforcement. Methods: Quarterly sales data of J01 antibacterial for systemic use in standard units were obtained from the IQVIA-MIDAS database, spanning from the first quarter of 2016 to the last quarter of 2020. Antibiotics consumption was measured in defined daily doses per 1,000 inhabitant per day- in a quarter (DDDdq). A comparative analysis of antibiotic consumption pre- and post-policy periods introduction was conducted by computing the average consumption values for each period. Statistical comparison of the mean differences between the two periods were then made using independent samples t-test, Mann-Whitney U Test where needed. Time series analysis was employed to estimate the projected antibiotic consumption in the post-policy period if the restriction policy had not been implemented, which was then compared to actual consumption values to evaluate the effectiveness of the restriction policy. Results: During the pre-policy, there were seasonal trends of the total and oral antibiotic consumption through quarters, with higher consumption observed in the first and fourth quarters. In contrast, parenteral antibiotic consumption did not appear to follow a clear seasonal pattern. Following the restriction policy, there was a significant reduction in total and oral antibiotic use, with mean reductions of -96.9 DDDdq (p-value = 0.002) and -98 DDDdq (p-value = 0.002), respectively. Conversely, a significant increase in parenteral antibiotic consumption was observed with a mean increase of +1.4 DDDdq (p-value < 0.0001). The comparison between the forecasted and actual models showed that the actual antibiotics consumption for total, oral, and parenteral were lower than the corresponding forecasted values by 30%, 31%, and 34%, respectively. Conclusion: Overall, our analysis of antibiotics consumption from 2016 to 2020 displays great success for the policy implemented by the Saudi Ministry of Health in significantly reducing the total and oral use of antibiotics. However, future studies are needed to explore the increased consumption of the parenteral antibiotics as well as the persistent high consumption patterns during the fall and winter months even after the implementation of the restriction policy.

Functional outcomes between headache surgery and targeted botox injections: A prospective multicenter pilot study.

Introduction: Chronic migraine headaches (MH) are a principal cause of disability worldwide. This study evaluated and compared functional outcomes after peripheral trigger point deactivation surgery or botulinum neurotoxin A (BTA) treatment in patients with MH. Methods: A long-term, multicenter, and prospective study was performed. Patients with chronic migraine were recruited at the Ohio State University and Massachusetts General Hospital and included in each treatment group according to their preference (BTA or surgery). Assessment tools including the Migraine Headache Index (MHI), Migraine Disability Assessment Questionnaire (MIDAS) total, MIDAS A, MIDAS B, Migraine Work and Productivity Loss Questionnaire-question 7 (MWPLQ7), and Migraine-Specific Quality of Life Questionnaire (MSQ) version 2.1 were used to evaluate functional outcomes. Patients were evaluated prior to treatment and at 1, 2, and 2.5 years after treatment. Results: A total of 44 patients were included in the study (surgery=33, BTA=11). Patients treated surgically showed statistically significant improvement in headache intensity as measured on MIDAS B (p = 0.0464) and reduced disability as measured on MWPLQ7 (p = 0.0120) compared to those treated with BTA injection. No statistical difference between groups was found for the remaining functional outcomes. Mean scores significantly improved over time independently of treatment for MHI, MIDAS total, MIDAS A, MIDAS B, and MWPLQ 7 (p<0.05). However, no difference in mean scores over time was observed for MSQ. Conclusions: Headache surgery and targeted BTA injections are both effective means of addressing peripheral trigger sites causing headache pain. However, lower pain intensity and work-related disabilities were found in the surgical group.

Effect of Pranayama as Adjuvant to Medical Treatment on Severity, Frequency, and Duration of Headache in Migraine Patients: An Open-Label Randomized Controlled Trial.

Background: Migraine is the second leading cause of disability worldwide with high rates of dissatisfaction for allopathic treatment among patients. Pranayama is an easy, convenient, and cost-effective method that can supplement existing standard medical treatment of migraine. Objective: To study the effect of pranayama as an adjuvant to standard medical treatment of migraine on clinical outcome variables of migraine. Materials and Methods: This was a randomized controlled trial conducted on 80 consecutive migraine patients who were diagnosed as per International Classification of Headache Disorders-3 (ICHD-3) criteria and were randomly allocated into two groups, that is, standard medical treatment (SMT) group and standard medical treatment plus pranayama (SMT + P) group. The effect of pranayama on clinical outcome variables of migraine was evaluated by using standardized questionnaires. The data was statistically analyzed using SPSS Statistics 20 software. A P value of ≤0.05 was considered statistically significant. Results: Intragroup analysis showed all clinical outcome variables of migraine reduced significantly in the SMT + P group whereas all clinical outcome variables of migraine except the duration of headache episodes reduced significantly in the SMT group. Although statistically non-significant, intergroup analysis demonstrates that reduction in headache severity, duration of headache episodes, and headache impact test-6 (HIT-6) score was more in the SMT + P group whereas reduction in headache frequency and migraine disability assessment (MIDAS) score was more in the SMT group. Conclusion: Pranayama supplements the standard medical treatment of migraine by reducing the duration of headache episodes in addition to the reduction in headache severity, headache frequency, HIT-6 scores, and MIDAS scores.