Prevalence of primary headaches in multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is the most common immune-mediated inflammatory disease of the central nervous system. It is characterized by symptoms such as visual disturbances, paresis with spasticity, paresthesia, numbness, and fatigue. However, several studies have shown a high prevalence of headaches in individuals with MS. Migraine and tension-type headaches are the most frequent types of headaches experienced by those with MS. Additionally, the role of MS disease-modifying agents must be considered. These agents have different modes of action and side effect profiles, and their use may sometimes trigger headaches in patients with MS. OBJECTIVES: This study aimed to explore the prevalence and clinical characteristics of primary headaches in MS patients. The relationship between headache and clinical features of MS (Course of MS, duration, EDSS, brain imaging and DMD) are also investigated. SUBJECTS AND METHODS: Two hundred and eighty-one MS patients diagnosed according to according to the 2017 revisions to the McDonald Criteria were included in the study. Data was collected from the MS unit medical records and from the interview with the patients. Patients with reported headaches are asked to recall their headache characteristics and patterns using an interviewer administered Arabic language-structured validated questionnaire. RESULTS: The median age of patients was 33 years old, with a range of 22-55. Tension-type headache (TTH) was more common in males, patients with more severe disability (EDSS ≥ 3), and those with SPMS and PPMS phenotypes. Additionally, patients on rituximab or cyclophosphamide therapy were more likely to have TTH. On the other hand, females, patients with milder disability (EDSS < 3), and those with RRMS phenotype were more likely to have migraine. This was also true for patients with MRI lesions involving the periaqueductal gray, and those receiving INF or fingolimod (P < 0.05). Periaqueductal gray matter lesions were found in the MRI of 48 patients (40 %) who experienced headaches on more than 10 days per month. Sensorimotor lesions in the brain were found in 55 patients (53.4 %) with severe headaches (p-value < 0.001). Interferons were associated with an increased risk of worsening preexisting headaches and the appearance of de novo headaches related to its intake (odds ratio: 2.84, 3.72; relative risk: 1.63, 2.04; p-value = 0.03, < 0.001, respectively). On the other hand, rituximab was associated with a decreased risk of worsening preexisting headaches and the appearance of de novo headaches related to its intake (odds ratio: 0.04, 0.09; relative risk: 0.11, 0.18; p-value = < 0.001, < 0.001, respectively). CONCLUSION: Primary headaches are a common occurrence in patients with MS. Migraines and tension-type headaches (TTH) are among the most prevalent types. It has been observed that interferon can exacerbate preexisting headaches and even cause new ones. Additionally, the location of MS plaques may play a role in the frequency and severity of headaches.

Scholarly Activity and Gender of an Applicant for a General Surgery Residency.

INTRODUCTION: Applying to general surgery residency is undoubtedly a competitive process. Participation in scholarly activity (SCA) has been cited as a criterion when selecting applicants for interview and in the ranking process. This study aims to evaluate the association between gender of applicants to surgery residency and SCA and to characterize trends in SCAs over time. METHODS: We analyzed the SCA of applicants interviewed at a general surgery residency program over 6-interview cycles (2016-2021). Eight SCA categories were included: (1) Poster Presentation, (2) Oral Presentation, (3) Peer-Reviewed (PR) Journal Articles/Abstracts, (4) PR Journal Articles/Abstracts (Other than Published), (5) PR Online Publication, (6) PR Book Chapter, (7) Nonpeer reviewed Online Publication, and (8) Other Articles/Scientific Monograph. RESULTS: Of a total of 335 interviewed applicants, 288 (86%) had at least one count of SCA. Overall, no difference between male and female applicants was noticed (n = 178, 84.8% versus n = 110, 88%, P = 0.409) and no change in percentage of SCA over the six cycles (P = 0.239). The most reported SCAs were poster presentations (n = 242, 72.2%), oral presentations (n = 159, 47.5%), PR journal articles/abstracts (n = 159, 47.5%). Female applicants have marginally higher median (interquartile range) for SCAs compared to male applicants (5 [3, 8] versus 4 [3, 8], P value 0.272). CONCLUSIONS: No association between gender and SCA among applicants for general surgery residency positions was observed. While more than three-fourths of applicants have at least one SCA, only a small fraction of applicants were published. Students should be made aware of the importance of SCA early in graduate medical education.

Cerebral protection strategies for type A aortic dissection repair.

Importance: Techniques to preserve neurological function during type A aortic dissection repairs have been broadly discussed in the literature and heavily debated. Despite the effectiveness of various approaches, a consensus lacks on how to maintain optimal cerebral temperature during surgery. This review examines the three predominant cerebral protection strategies in aortic arch reconstructions: straight deep hypothermic circulatory arrest (sDHCA), retrograde cerebral perfusion (RCP), and antegrade cerebral perfusion (ACP). Observations: The signature characteristics of sDHCA, RCP, and ACP are similar-hypothermia, with or without cerebral perfusion. Employing cerebral perfusion techniques may prolong operative times, while ACP permits operation at higher body temperatures, albeit with restricted operative durations. Conclusion: For type A dissection arch reconstructions, sDHCA, RCP, and ACP can be successfully implemented. Factors such as operative times and individual patient conditions should be considered when choosing a cerebral protection strategy.

Are There Racial Differences in the Rate of Surgical Site Infection Based on Surgical Subspecialty?

Background: Surgical site infection (SSI) is a common, morbid post-operative complication. We hypothesized the presence of racial differences in SSI rates, comparing black/African American (BAA) to white non-Hispanic (WNH) patients. Patients and Methods: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2017), BAA and WNH surgery patients across 10 surgical specialties were identified: general surgery (GS), vascular surgery (VS), cardiac surgery (CS), thoracic surgery (TS), orthopedics (OS), neurosurgery (NS), urology (US), otolaryngology (ENT), plastic surgery (PS), and gynecology (GYN). The primary outcome was SSI rate (superficial, deep incisional, or organ/space). The secondary outcome was rate of non-surgical infection. Pearson χ2 and Fisher exact tests were used to test group differences of categorical variables. Continuous variables were tested with the Student t-test, or Mann-Whitney U test, with statistical significance set at a value of p < 0.05. Multivariable logistic regression models were conducted to analyze the association between race/ethnicity and the infection outcomes. Results: A total of 740,144 patients were included: 99,425 (13.4%) BAA and 640,749 (86.6%) WNH, distributed as follows; 32,2976 GS, 17,6175 OS, 44,383 VS, 2,227 CS, 9,645 TS, 42,298 NS, 42,726 US, 18,518 ENT, 20,709 PS, and 60,517 GYN cases. Surgical site infection rates were higher among WNH in GS (4.4% vs. 4.1%; p = 0.003) and TS (3.1% vs. 1.7%; p = 0.015); lower in VS (3.2% vs. 4.4%; p < 0.001), OS (1.2% vs.1.6%; p < 0.001), and GYN (2.4% vs. 3%; p < 0.001); and similar between WNH and BAA in ENT (1.8% vs 1.8%; p = 0.76), and US (1.9% vs. 1.9%; p = 0.90). Non-surgical infection was higher in BAA in NS (3.2% vs. 2.5%; p = 0.003), and higher in WNH in GYN (2.6% vs. 2%; p < 0.001), OS (1.7% vs. 1.1%; p < 0.001), US (4.4% vs. 3.6%; p = 0.014), and VS (3.4% vs. 2.6%; p < 0.001). Conclusions: Variation exists in SSI rates between WNH and BAA patients among surgical subspecialties. Further research is required to understand these differences and address racial disparities in outcomes.

Non-nutritive Sweeteners: Weight Loss or Weight Gain?

The consumption of non-nutritive sweeteners (NNS) is on the rise among different populations. In parallel, the debate about their potential health benefits and risks remains inconclusive. Numerous published studies elucidate the impact of NNS on general health, weight control, and the risk of certain diseases. However, no definitive conclusions regarding the effect of chronic NNS use on weight have been reached in humans. This review summarizes current evidence related to the biological role of NNS and their subsequent effects on weight. The mechanisms of action through which NNS impact weight are discussed, including their effect on sweet taste receptors, cognition, metabolic and endocrine functions, intestinal microbiota, and adiposity. Conflicting evidence is hindering the formulation of precise recommendations, but the evidence opposing the use of NNS remains weak, and the ultimate impact on weight largely relies on several other behavioral patterns.

Sensitivity and specificity of alternative screening methods for systematic reviews using text mining tools.

OBJECTIVES: To evaluate the impact of text mining (TM) on the sensitivity and specificity of title and abstract screening strategies for systematic reviews (SRs). STUDY DESIGN AND SETTING: Twenty reviewers each evaluated a 500-citation set. We compared five screening methods: conventional double screen (CDS), single screen, double screen with TM, combined double screen and single screen with TM, and single screen with TM. Rayyan, Abstrackr, and SWIFT-Review were used for each TM method. The results of a published SR were used as the reference standard. RESULTS: The mean sensitivity and specificity achieved by CDS were 97.0% (95% confidence interval [CI]: 94.7, 99.3) and 95.0% (95% CI: 93.0, 97.1). When compared with single screen, CDS provided a greater sensitivity without a decrease in specificity. Rayyan, Abstrackr, and SWIFT-Review identified all relevant studies. Specificity was often higher for TM-assisted methods than that for CDS, although with mean differences of only one-to-two percentage points. For every 500 citations not requiring manual screening, 216 minutes (95% CI: 169, 264) could be saved. CONCLUSION: TM-assisted screening methods resulted in similar sensitivity and modestly improved specificity as compared to CDS. The time saved with TM makes this a promising new tool for SR.

The importance of USMLE step 2 on the screening and selection of applicants for general surgery residency positions.

Background: As announced by the Federation of State Medical Boards (FSMB) and National Board of Medical Examiners (NBME), the United States Medical Licensing Examination (USMLE) Step 1 score reporting has transitioned to pass/fail outcomes instead of the traditional numeric score after January 26, 2022. USMLE Step 1 scores have been used widely as a crucial tool in screening and selecting applicants for residency programs. This study aims to determine the role of USMLE Step 2 in the selection of applicants for general surgery residency. Methods: A retrospective study was conducted over six recruiting cycles from 2016 to 2021. The data from 334 interviewed applicants from one general surgery residency program were assessed. Data analyzed included USMLE Step 1 and Step 2 scores, applicant gender, Alpha Omega Alpha (AOA) status, letters of recommendation (LOR), and research/publications (RS). Results: Of the 334 interviewed applicants, 209 (62.6%) were male. The mean [SD] USMLE Step 1 and USMLE Step 2 C K (Clinical Knowledge) scores were 239.6 [±10.4] and 249.2 [±11.4], respectively. The mean (SD) LOR and RS scores were 4.24 [±0.4] and 3.9 [±0.7], respectively. A positive correlation was observed between USMLE Step 1 and USMLE Step 2 C K (Clinical Knowledge) scores (r = 0.60, p < .001), LOR scores (r = 0.24, p = .008), and AOA status (r = 0.19, p = .038). There was a negligible correlation between USMLE scores and applicant gender. Conclusion: Transitioning USMLE Step 1 to pass/fail will make the initial screening and selection process of applications challenging for residency programs. In the short term, USMLE Step 2 scores, LOR, and AOA status are important as screening assessments. Valid measures to ensure appropriate, equitable, and fair assessments are needed.

Testosterone Coordinates Gene Expression Across Different Tissues to Produce Carotenoid-Based Red Ornamentation.

Carotenoid pigments underlie most of the red, orange, and yellow visual signals used in mate choice in vertebrates. However, many of the underlying processes surrounding the production of carotenoid-based traits remain unclear due to the complex nature of carotenoid uptake, metabolism, and deposition across tissues. Here, we leverage the ability to experimentally induce the production of a carotenoid-based red plumage patch in the red-backed fairywren (Malurus melanocephalus), a songbird in which red plumage is an important male sexual signal. We experimentally elevated testosterone in unornamented males lacking red plumage to induce the production of ornamentation and compared gene expression in both the liver and feather follicles between unornamented control males, testosterone-implanted males, and naturally ornamented males. We show that testosterone upregulates the expression of CYP2J19, a gene known to be involved in ketocarotenoid metabolism, and a putative carotenoid processing gene (ELOVL6) in the liver, and also regulates the expression of putative carotenoid transporter genes in red feather follicles on the back, including ABCG1. In black feathers, carotenoid-related genes are downregulated and melanin genes upregulated, but we find that carotenoids are still present in the feathers. This may be due to the activity of the carotenoid-cleaving enzyme BCO2 in black feathers. Our study provides a first working model of a pathway for carotenoid-based trait production in free-living birds, implicates testosterone as a key regulator of carotenoid-associated gene expression, and suggests hormones may coordinate the many processes that underlie the production of these traits across multiple tissues.

Lead exposure is correlated with reduced nesting success of an urban songbird.

Lead exposure is a concern in urban ecosystems, with physiological and behavioral effects well documented in humans. Wildlife inhabiting urban ecosystems are also exposed to lead, yet little work has documented the sublethal effects of lead exposure in urban wildlife. We studied northern mockingbirds (Mimus polyglottos) in three neighborhoods of New Orleans, Louisiana, two with high soil lead and one with low soil lead, to better understand how lead exposure may influence mockingbirds' reproductive biology. We monitored nesting attempts, measured lead concentrations in blood and feathers of nestling mockingbirds, documented egg hatching and nesting success, and assessed rates of sexual promiscuity in relation to neighborhood soil lead levels. We found that nestling mockingbirds' blood and feather lead levels reflected the soil lead levels of their neighborhoods and nestling blood lead levels were similar to those of adult mockingbirds in the same neighborhoods. Nest success, as evaluated by daily nest survival rates, was higher in the lower lead neighborhood. Clutch sizes varied substantially across neighborhoods, but rates of unhatched eggs did not covary with neighborhood lead levels, suggesting that other drivers are influencing variation in clutch sizes and hatching success in urban habitats. At least one-third of nestling mockingbirds were sired by an extra-pair male, and there was no relationship between extra-pair paternity rates and neighborhood lead levels. This study provides insight on how lead contamination may influence reproduction in urban-dwelling wildlife and suggests that nestling birds could serve as useful bioindicators of lead levels in urban neighborhoods.

Perforated appendicitis: The solution to pollution is not dilution.

BACKGROUND: Surgical dogma states that the "solution to pollution is dilution." We hypothesized that withholding irrigation during pediatric Single Incision Laparoscopic Surgery (SILS) appendectomies for perforated appendicitis would decrease postoperative abscess rate. METHODS: From May 2011 to 5/2015, during SILS appendectomies, saline irrigation and suctioning was performed. From June 2015 to 8/2021, only suctioning was performed. The operations and peri-operative management were otherwise identical. We retrospectively reviewed 46 patients in the Irrigation (I) Group and 91 patients in the Non-Irrigation (NI) Group. RESULTS: Abscess rate decreased from 19.6% in Group I to 9.9% in Group NI, but this did not reach statistical significance (p = 0.12). Operative duration was significantly longer in patients who developed postoperative abscesses in Group NI (odds ratio 1.67, p = 0.002) and overall (odds ratio 1.45, p = 0.0002). CONCLUSIONS: Withholding irrigation during SILS appendectomies trended toward a decreased postoperative abscess rate. Increased operative times were associated with postoperative abscess formation.

Unexpected long-term retention of subcutaneous beeswax implants and additional notes on dose and composition from four testosterone implant studies.

Experimental manipulations of testosterone have advanced our understanding of the hormonal control of traits across vertebrates. Implants are commonly used to supplement testosterone and other hormones to organisms, as they can be readily scaled to produce desired hormone levels in circulation. Concerns about pharmacological (i.e. unnatural) doses of traditional silastic implants led to innovation in implant methods, with time-release pellets and beeswax implants proposed as solutions. A study comparing silastic, time-release pellets, and beeswax implants found the latter to be most effective in delivering a physiologically relevant dose. One proposed advantage to subcutaneous beeswax implants is that they are expected to degrade within the body, thus removing the obligation to recapture implanted individuals in the field. However, few studies have reported on dosage and no published literature has examined the assumption that beeswax implants readily degrade as expected. Here we present time-release androgen data in relation to implants containing varying levels of testosterone from four separate implant studies. In addition, we report long-term persistence of subcutaneous implants, including two cases of implants being retained for > 2 years. Finally, we offer recommendations on the composition and implementation of beeswax implants to aid the pursuit of minimally invasive and physiologically relevant manipulations of circulating hormones.

Case report: Multimodal neoadjuvant and adjuvant chemotherapy for hepatic undifferentiated embryonal sarcoma in a young adult.

Hepatic undifferentiated embryonal sarcoma of the liver (UESL) is a rare hepatic malignancy found more commonly in pediatric patients. It has been associated with poor outcomes in adults and the role and timing of systemic therapy is unclear. There have been very few case reports detailing combination neoadjuvant and adjuvant chemotherapy use for hepatic undifferentiated embryonal sarcoma in adults. In this report, a 22-year-old male admitted with right upper quadrant pain was diagnosed with a 20 x 10 x 10 cm well-circumscribed, highly vascularized hepatic mass in the entirety of the left lobe. Biopsy confirmed the diagnosis of UESL. PET/CT showed no evidence of metastatic disease, and he received four cycles of Doxorubicin and Ifosfamide with demonstrated reduction in size and decrease in PET avidity. He underwent left hepatectomy with periportal lymphadenectomy, cholecystectomy, and partial gastrectomy with negative margins and received adjuvant Doxorubicin, Ifosfamide and Mesna. At 48 months, the patient was alive without evidence of disease. We hereby emphasize the potential advantages of combination chemotherapy and surgical resection in the management of UESL in adults.

Management of Native Lung Malignancy in a Lung Transplant Recipient.

A 75-year-old male patient with a history of previous right lung transplant presented with left upper lobe squamous cell carcinoma. Endobronchial ultrasound and positron emission tomography displayed no mediastinal lymphadenopathy. A ventilation-perfusion scan displayed minimal perfusion to the native lung. Left robot-assisted lysis of adhesions, decortication, left upper lobectomy, and mediastinal lymphadenectomy were performed. The patient tolerated the procedure well. Final pathology displayed pT2a, n0, m0. Lobectomy is a safe and efficient treatment of native lung malignancy in the setting of previous lung transplant with minimally functioning native lung.

Resident Autonomy and Performance Independence in Surgical Training Are Time- and Skill-Dependent.

INTRODUCTION: Appropriate faculty supervision and conditional independence of residents during training are required for autonomous and independent postgraduate practice. However, there is a growing concern that competence for transition to independent practice is not universally met. We hypothesize that surgery residents play a significant and active role in achieving their own independent status. METHODS: Over seven academic years (July 2014 through June 2021), 46 surgeons supervised and intraoperatively assessed the performance of 51 residents using validated Objective Structured Assessment of Technical Skill (OSATS) and Zwisch Operative Autonomy (ROA) assessments. Resident readiness to perform procedures independently (RRI) was graded as yes, no, or not applicable. Data were analyzed using descriptive statistics with categorical variables reported as frequencies and percentages. RESULTS: A total of 1657 elective procedures were performed by residents supervised by faculty. Association between RRI and postgraduate year (PGY), OSATS scores, ROA, resident and faculty gender, and case complexity was analyzed. Results indicated positive correlation between RRI and summative OSATS score (r = 0.510, P < 0.001), PGY (r = 0.535, P < 0.001) and ROA (r = 0.473, P < 0.001). Percentage of overall RRI increased from 7% at PGY1 to 87.4% at PGY5. Meaningful autonomy ratings increased from 23.6% at PGY1 to 92.5% at PGY5. Variations in ratings was observed when considering case category and complexity. CONCLUSIONS: RRI increases with years of training with variation when considering the specialty/The Accreditation Council for Graduate Medical Education procedure category and the complexity of cases. Specialty fellowships are a viable option to address the gap in The Accreditation Council for Graduate Medical Education categories when residency alone cannot reach appropriate independence. Residents' technical skills play a crucial role in evaluating RRI and granting operative autonomy.

Shared Decision-Making in Pancreatic Surgery.

Objective: The objective of this study is to determine the factors influencing pancreatic surgery patients' perceptions of the shared decision-making process (SDM). Background: Decision-making in pancreatic surgery is complicated by the risk of morbidity and mortality and risk of early recurrence of disease. Improvement in SDM has the potential to improve the receipt of goal- and value-concordant care. Methods: This cross-sectional survey included patients who underwent pancreatic surgery. The following components were studied in relation to SDM: modified satisfaction with decision scale (SWD), modified decisional regret scale (DRS), quality of physician and patient interaction, and the impact of quality of life (FACT-Hep). Correlations were computed using Pearson's correlation score and a regression model. Results: The survey completion rate was 72.2% (of 40/55) and the majority (72.5%) of patients underwent pancreaticoduodenectomy. There were significant positive relationships between the SDM measure and (DRS, SWD; r = 0.70, P < 0.001) and responses to questions regarding how well the patient's actual recovery matched their expectations before treatment (r = 0.62, P < 0.001). The quality of the physician-patient relationship correlated with how well recovery matched expectations (r = 0.53, P = 0.002). SDM measure scores were significant predictors of the decision evaluation measure (R2(adj) = 0.48, P < 0.001), FACT-Hep (R2(adj) = 0.15, P < 0.001), and recovery expectations measure (R2(adj) = 0.37, P < 0.001). Conclusions: Improved SDM in pancreatic surgery is associated with more realistic recovery expectations, decreased decisional regret, and improved quality of life.

A complete ab initio thermodynamic and kinetic catalogue of the defect chemistry of hematite α-Fe2O3, its cation diffusion, and sample donor dopants.

This paper studies comprehensively the defect chemistry of and cation diffusion in α-Fe2O3. Defect formation energies and migration barriers are calculated using density functional theory with a theoretically calibrated Hubbard U correction. The established model shows a good agreement with experimental off-stoichiometry and cation diffusivities available in the literature. At any temperature, and are the predominant ionic defects in hematite at the two extremes of oxygen partial pressure (pO2) range, reducing and oxidizing, respectively. Between these two extremes, an intrinsic electronic regime exists where small polaronic electrons and holes are the dominant charge carriers. The calculated migration barriers show that Fe ions favor the diffusion along the 〈111〉 direction in the primitive cell through an interstitial crowdion-like mechanism. Our model suggests that cation diffusion in hematite is mainly controlled by the migration of , while may contribute to cation diffusion at extremely low pO2. Our analysis in the presence of two sample donor dopants Ti and Sn indicates that high temperature annealing at T > 1100 K is needed to prepare n-type hematite at ambient pO2, consistently with prior experimental findings. Alternatively, annealing at lower temperatures requires much lower pO2 to avoid compensating the donors with Fe vacancies. A synergistic comparison of our theoretical model and the experimental results on Ti-doped hematite led us to propose that free electrons and small polarons coexist and both contribute to n-type conductivity. Our validated model of defective hematite is a foundation to study hematite in applications such as corrosion and water splitting.

Testosterone regulates CYP2J19-linked carotenoid signal expression in male red-backed fairywrens (Malurus melanocephalus).

Carotenoid pigments produce most red, orange and yellow colours in vertebrates. This coloration can serve as an honest signal of quality that mediates social and mating interactions, but our understanding of the underlying mechanisms that control carotenoid signal production, including how different physiological pathways interact to shape and maintain these signals, remains incomplete. We investigated the role of testosterone in mediating gene expression associated with a red plumage sexual signal in red-backed fairywrens (Malurus melanocephalus). In this species, males within a single population can flexibly produce either red/black nuptial plumage or female-like brown plumage. Combining correlational analyses with a field-based testosterone implant experiment and quantitative polymerase chain reaction, we show that testosterone mediates expression of carotenoid-based plumage in part by regulating expression of CYP2J19, a ketolase gene associated with ketocarotenoid metabolism and pigmentation in birds. This is, to our knowledge, the first time that hormonal regulation of a specific genetic locus has been linked to carotenoid production in a natural context, revealing how endocrine mechanisms produce sexual signals that shape reproductive success.

Induction of Profibrotic Microenvironment via TLR4 MyD88-Dependent and -Independent Inflammatory Signaling in Chronic Hepatitis C Virus Infection.

Hepatitis C virus (HCV) is a well-known pathogen to establish chronic infection leading to end-stage liver disease. The destruction of liver tissues takes its roots under chronic inflammation and proinflammatory signaling in liver microenvironment. The viral proteins interact with certain pattern recognition receptors, including Toll-like receptors, activating the innate immune system to clear the virus. HCV achieves immune evasion through other mechanisms and induce a continuous inflammatory microenvironment via Kupffer cells and Hepatic Stellate cells. This promotes disease progression. The current study aims to elucidate that the role of Toll-like receptor 4 (TLR4) induced innate immune response in chronic inflammation in patients chronically infected with HCV. For this purpose, changes in downstream signaling cascade of TLR4 during chronic HCV infection using peripheral blood mononuclear cells of chronic HCV patients were studied. We found significant increase in expression levels of proinflammatory and profibrotic genes induced by TLR4 Myeloid differentiation factor 88 (MyD88)-dependent pathway between treatment naive and healthy controls, while no significant difference between the expressions of genes involved in TLR4 signaling was found between treatment responders and healthy controls. Interestingly, both TLR4 MyD88-dependent and -independent pathways were found to be operational in nonresponders to interferon treatment. This further strengthens the involvement of innate immune signaling as a leading factor in HCV-mediated liver disease progression and the role of TLR4 MyD88-dependent and -independent pathway in ensuring the conditions for chronic inflammation.

Tuning metal oxide defect chemistry by thermochemical quenching.

The low-temperature defect chemistry of monoclinic and tetragonal ZrO2 and hematite Fe2O3 is studied in the non-equilibrium state of thermochemical quenching; that is, rapid cooling starting from a certain high temperature and oxygen chemical potential. This non-equilibrium state is of great interest because many metal oxides are used at low temperatures below their growth temperatures. This paper addresses the importance of considering this non-equilibrium state rather than applying equilibrium thermodynamics as commonly used when studying point defects from first principles. Based on point defect formation energies calculated previously using density functional theory, we compare the type of dominant defects at equilibrium to those at a quenched state originating from a certain initial growth temperature and oxygen partial pressure. The comparison is facilitated by casting the dominant defects in a dominance diagram on the temperature - oxygen partial pressure plane. We consider two scenarios to model the quenched state. In the first, only electronic defects equilibrate whereas all ionic defects are frozen. Whereas, in the second, electronic defects and interstitials are allowed to equilibrate under the assumption of mobile interstitials at low temperatures. We find that new ionic charge compensation modes can appear on the dominance diagram after quenching. Additionally, purely ionic charge compensation modes consisting of vacancies and/or interstitials expand in the dominance diagram at the expense of purely electronic compensation modes. For the ZrO2 phases, we argue that scenario 2 is more realistic and leads to difficulty in achieving n-type doping by thermochemical quenching. For Fe2O3, and regardless of the quenching scenario, iron vacancies occupy a wider zone of domination, which limits the performance of this oxide as a water splitting photoanode. Our study shows that by controlling the growth thermochemical conditions, it is possible to tune the Fermi level of oxides over a considerable range within the band gap by quenching. This provides an extra tool to tune the electric conductivity of metal oxides beyond traditional extrinsic doping. This work indicates that non-equilibrium thermodynamic analysis is necessary to understand and control defect chemistry at low temperatures.

Vitamin D status of untreated children and adolescent Egyptian patients with genetic generalized epilepsy: A case-control study.

PURPOSE: Antiepileptic drugs (AEDs) are commonly incriminated for vitamin D deficiency in children with epilepsy. The aim of this study was to examine 25(OH) vitamin D status among children and adolescents with genetic generalized epilepsy (GGE) who had never received AEDs and its relation to seizure frequency and epilepsy duration. METHODS: This case-control study was conducted on 42 recently diagnosed patients with GGE, aged ≤18 years and 40 age- and gender-matched controls. Serum 25(OH) vitamin D level was performed for all participants. RESULTS: Serum 25(OH) vitamin D level was significantly lower in patients (median = 22 ng/ml, interquartile range (IQR) = 16.6-28.6) compared with controls (median = 58.4 ng/ml, IQR = 53-68), (P-value < 0.001). Patients with ≥4 seizures per month had a significantly lower level of serum 25(OH) vitamin D (median = 17.7 ng/ml, IQR = 16-24) than patients with lower seizure frequency (median = 28.3 ng/ml, IQR = 24.2-40.2), (P-value = 0.004). Also, there was a statistically significant negative correlation between the duration of epilepsy and serum 25(OH) vitamin D level (r = -0.309, P-value = 0.046). The receiver operating characteristic curve analysis showed that serum 25(OH) vitamin D level with a cutoff value of 23.9 distinguished patients with low seizure frequency (five or less per year) from patients with higher seizure frequency with a sensitivity and specificity of 80% and 74%, respectively (area under the curve (AUC) = 0.798). CONCLUSION: Vitamin D deficiency is found in treatment-naive children with epilepsy and adolescents with GGE, and it is associated with higher seizure frequency, longer disease duration, and younger age at onset.