Acute effects of mango leaf extract on cognitive function in healthy adults: a randomised, double-blind, placebo-controlled crossover study.

Introduction: Extracts made from the leaves of the edible mango plant (Mangifera indica L., Anacardiaceae) have a long history of medicinal usage, most likely due to the presence of high levels of mangiferin, a polyphenol compound. Previous research has demonstrated that mango leaf extract (MLE) can beneficially modulate cognitive function in both animals and humans. This study aimed to assess the effects of an acute dose of 300 mg MLE (standardised to contain ≥60% mangiferin) on cognitive performance and mood in healthy adults. Methods: In this double-blind, placebo-controlled, crossover study, 114 healthy men and women (18-43 years) received either MLE or a matched placebo at each testing visit (separated by at least 7 days). Cognitive performance (including the cognitive demand battery) and mood were measured at 30, 180, and 300 min post-dose. Results: The results showed that, compared to placebo, the group taking MLE displayed a significant increase in serial 3 s and serial 7 s subtraction errors overall. There were no other significant effects on cognitive performance. Discussion: The results of the current study suggest that the consumption of 300 mg MLE in the absence of an observed multitasking psychological stressor does not improve cognitive performance or mood at up to 300 min post-dose. Due to the very limited nature of the effects and since they were observed among many analyses, these findings should be treated with caution.Clinical trial registration: http://ClinicalTrials.gov, identifier [NCT05182450].

The Association Between Well-Being and Empathy in Medical Residents: A Cross-Sectional Survey.

Objective: To evaluate the extent to which personal well-being may be associated with empathy, while controlling for potential confounders. Settings/Location: Residency programs throughout the United States. Subjects: A total of 407 medical residents from residencies including general medicine, surgery, specialized and diagnostic medicine participated in this study. Outcome Measures: Well-being was measured using the modified existential well-being subscale of the spiritual well-being scale. Empathy was measured using the Jefferson Scale of Empathy. Results: Well-being was found to be positively correlated with empathy when adjusted for possible confounders (p < 0.001). In addition to well-being, other factors noted to be statistically significant contributors to higher empathy scores while controlling for the others included age, gender, year in residency, specialty, and work-hours (p < 0.05 for each). After controlling for these factors, a resident's year in residency was not found to be a statistically significant contributor to empathy score. Conclusions: In this study, well-being was associated with empathy in medical and surgical residents. Empathy is a fundamental component of physician competency, and its development is an essential aspect of medical training. These findings suggest that efforts to increase well-being may promote empathy among medical residents.

Acute Cognitive Performance and Mood Effects of Coffeeberry Extract: A Randomized, Double Blind, Placebo-Controlled Crossover Study in Healthy Humans.

BACKGROUND: Coffeeberry extract, rich in chlorogenic acids, shows promise in improving mood and cognition, particularly when co-supplemented with phenolic compounds. However, limited work has considered the effects of coffeeberry in isolation, especially at low doses. OBJECTIVE: The current study investigated the effect of low and moderate doses of coffeeberry extract on cognition and mood. DESIGN: This randomized, double-blind, placebo-controlled crossover design investigated three active beverages on a sample of 72 healthy adults aged 18-49 years. The investigational beverages contained 100 mg or 300 mg coffeeberry extract (standardized to 40% chlorogenic acid), or 75 mg caffeine (positive control). Cognition, mood, and subjective energy were measured at baseline and then again at 60 and 120 min post-treatment. RESULTS: Analysis revealed no effect of 300 mg coffeeberry extract, while 100 mg resulted in increased mental fatigue during the performance of cognitively demanding tasks (p = 0.025) and decreased accuracy on a task of sustained attention (p = 0.003), compared to placebo, at 60 min post dose. CONCLUSIONS: Administration of 100 mg and 300 mg coffeeberry extracts revealed limited, transient negative effects following 100 mg coffeeberry. Given the large number of outcome measures analysed and the absence of findings following the 300 mg dose, these negative findings should be interpreted with caution. Overall, the findings of the current study suggest that coffeeberry extract at a low or moderate dose does not have a beneficial effect on mood, mental and physical energy levels, or cognition; higher doses, as have been administered previously, may be more effective.

Novel Model of Oxalate Diet-Induced Chronic Kidney Disease in Dahl-Salt-Sensitive Rats.

Diet-induced models of chronic kidney disease (CKD) offer several advantages, including clinical relevance and animal welfare, compared with surgical models. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. An increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction, and eventually CKD. Dahl-Salt-Sensitive (SS) rats are a common strain used to study hypertensive renal disease; however, the characterization of other diet-induced models on this background would allow for comparative studies of CKD within the same strain. In the present study, we hypothesized that SS rats on a low-salt, oxalate rich diet would have increased renal injury and serve as novel, clinically relevant and reproducible CKD rat models. Ten-week-old male SS rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks.Real-time PCR demonstrated an increased expression of inflammatory marker interleukin-6 (IL-6) (p < 0.0001) and fibrotic marker Timp-1 metalloproteinase (p < 0.0001) in the renal cortex of SS-OX rat kidneys compared with SS-NC. The immunohistochemistry of kidney tissue demonstrated an increase in CD-68 levels, a marker of macrophage infiltration in SS-OX rats (p < 0.001). In addition, SS-OX rats displayed increased 24 h urinary protein excretion (UPE) (p < 0.01) as well as significant elevations in plasma Cystatin C (p < 0.01). Furthermore, the oxalate diet induced hypertension (p < 0.05). A renin-angiotensin-aldosterone system (RAAS) profiling (via liquid chromatography-mass spectrometry; LC-MS) in the SS-OX plasma showed significant (p < 0.05) increases in multiple RAAS metabolites including angiotensin (1-5), angiotensin (1-7), and aldosterone. The oxalate diet induces significant renal inflammation, fibrosis, and renal dysfunction as well as RAAS activation and hypertension in SS rats compared with a normal chow diet. This study introduces a novel diet-induced model to study hypertension and CKD that is more clinically translatable and reproducible than the currently available models.

Evaluation of approaches to recruitment of racially and ethnically diverse breast cancer patients from an integrated health care setting for collection of observational social network data.

PURPOSE: We compared approaches to recruitment of diverse women with breast cancer in a study designed to collect complex social network data. METHODS: We recruited 440 women from the Kaiser Permanente Northern California population newly diagnosed with breast cancer, either in person at a clinic, by email, or by mailed letter. In clinic and mail recruitment, women completed a brief 3-page paper survey (epidemiologic data only), and women had the option to complete a separate, longer (30-40 min) personal social network survey online. In email recruitment, we administered epidemiologic and personal social network measures together in a single online survey. In email and mail recruitment, we limited the sample of non-Hispanic white (NHW) women to 30% of their total. We used descriptive analysis and multinomial logistic regression to examine odds of recruitment vs. mailed letter. RESULTS: Women responded to the social network surveys on average 3.7 months post-diagnosis. Mean age was 59.3 (median = 61.0). In-person clinic recruitment was superior with a 52.1% success rate of recruitment compared with 35.6% by mail or 17.3% by email (χ2 = 65.9, p < 0.001). Email recruitment produced the highest completion rate (82.1%) of personal network data compared with clinic (36.5%) or mail (28.7%), (χ2 = 114.6, p < 0.001). Despite intentional undersampling of NHW patients, response rates for Asian, Hispanic, and Black women by email were lower. However, we found no significant differences in recruitment rates by race and ethnicity for face-to-face clinic recruitment vs. by letter. Letter recruitment produced the highest overall response. CONCLUSION: Mailed letter was the best approach to representative recruitment of diverse women with breast cancer and collection of social network data, and further yielded the highest absolute response.

A metagenomic analysis of the virome of inverted papilloma and squamous cell carcinoma.

INTRODUCTION: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The role of human papillomavirus (HPV) in its pathogenesis has been controversial. The purpose of this study was to determine the virome associated with IP, with progression to carcinoma in situ (CIS), and invasive carcinoma. METHODS: To determine the HPV-specific types, a metagenomics assay that contains 62,886 probes targeting viral genomes in a microarray format was used. The platform screens DNA and RNA from fixed tissues from eight controls, 16 IP without dysplasia, five IP with CIS, and 13 IP-associated squamous cell carcinoma (IPSCC). Paired with next-generation sequencing, 48 types of HPV with 857 region-specific probes were interrogated against the tumors. RESULTS: The prevalence of HPV-16 was 14%, 42%, 70%, and 73% in control tissue, IP without dysplasia, IP with CIS, and IPSCC, respectively. The prevalence of HPV-18 had a similar progressive increase in prevalence, with 14%, 27%, 67%, and 74%, respectively. The assay allowed region-specific analysis, which identified the only oncogenic HPV-18 E6 to be statistically significant when compared with control tissue. The prevalence of HPV-18 E6 was 0% in control tissue, 25% in IP without dysplasia, 60% in IP with CIS, and 77% in IPSCC. CONCLUSIONS: There are over 200 HPV types that infect human epithelial cells, of which only a few are known to be high-risk. Our study demonstrated a trend of increasing prevalence of HPV-18 E6 that correlated with histologic severity, which is novel and supports a potential role for HPV in the pathogenesis of IP.

Radiofrequency Ablation for Chronic Lumbar Zygapophyseal Joint Pain Using a V-Shaped Active Tip Needle: An Observational Retrospective Study.

Background: Lumbar zygapophyseal joint dysfunction represents one of the major sources of chronic low back pain. Radiofrequency ablation (RFA) using a V-shaped active tip needle may offer a larger lesion of the medial branch nerves, improving clinical outcome. The aim of our study is to evaluate the efficacy and the feasibility of RFA using V-shaped active tip needles. Methods: This is a single-center observational retrospective study. Clinical records were screened and analyzed if they met the following inclusion criteria: adult patients (>18 years), diagnosis of chronic lumbar zygapophyseal joint pain, failure of conservative treatments, ability to provide informed consent for data analysis and publication. Exclusion criteria: lumbar pain not related to zygapophyseal joints, previous spinal/lumbar surgery, incomplete data, absence or withdrawal of informed consent. The primary outcome of the study was a change in pain intensity at follow-up. The secondary outcomes were the evaluation of quality-of-life improvement, the occurrence of adverse events and the impact on post-procedural analgesic consumption. For these purposes, pre- and post-treatment numeric rating scale (NRS), neuropathic pain 4 questions (DN4), EuroQoL - EQ-5D-3L, EQ-VAS, EQ-index and North American Spine Society (NASS) index were retrieved and analysed. Results: Sixty-four patients were included. 7.8% of patients at 1-month (CI95% 0.026, 0.173), 37.5% at 3-month (CI95% 0.257, 0.505), 40.6% at 6-month (CI95% 0.285, 0.536) and 35.9% at 9-month (CI95% 0.243, 0.489) follow-up reported a reduction of more than 80% in NRS Statistical analysis indicated a significant change in NRS, DN4, EQ-index and EQ-5D-VAS (p-value <0.001) at the different time-points. Conclusion: RFA using a V-shaped active tip needle might be a feasible and effective treatment for chronic lumbar zygapophyseal joint pain.

What is appropriate management for the contralateral uninvolved side in unilateral allergic fungal rhinosinusitis?

PURPOSE OF REVIEW: The aim of this article is to review the current literature regarding development of new or recurrent inflammation of uninvolved contralateral sinuses in unilateral allergic fungal rhinosinusitis (AFRS) and discuss management strategies. RECENT FINDINGS: AFRS is a subtype of chronic rhinosinusitis with nasal polyposis (CRSwNP) that can manifest as either unilateral or bilateral disease. Particular to AFRS compared with other CRSwNP subtypes is the high propensity for recurrence. Multiple recent studies have evaluated the recurrence rate of uninvolved contralateral sinuses in unilateral AFRS and demonstrated eventual involvement of the nondiseased side. Additionally, postoperative medical therapy of the nondiseased side reduced recurrence rates overall. SUMMARY: Recurrence of AFRS is high in both the ipsilateral and contralateral sinuses. Upfront bilateral medical and/or surgical treatment of patients presenting with unilateral AFRS may be considered to improve long-term inflammatory control.

Orbital resection by intranasal technique (ORBIT): A new classification system for reporting endoscopically resectable primary benign orbital tumors.

BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs. METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class. RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05). CONCLUSION: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs.

Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): In-depth sinus surgery analysis.

BACKGROUND: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in-depth assessment of surgery endpoints in SYNAPSE. METHODS: SYNAPSE was a double-blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count. RESULTS: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan-Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (<3 vs ≥3 years) since patients' last sinus surgery prior to study screening (hazard ratios [95% confidence intervals] 0.28 [0.09, 0.84] and 0.50 [0.26, 0.98], respectively) and baseline blood eosinophil count. CONCLUSIONS: Mepolizumab reduced the risk of further sinus surgery in patients with recurrent, refractory, severe CRSwNP, irrespective of the patient baseline characteristics assessed.

Mental Performance and Sport: Caffeine and Co-consumed Bioactive Ingredients.

The plant defence compound caffeine is widely consumed as a performance enhancer in a sporting context, with potential benefits expected in both physiological and psychological terms. However, although caffeine modestly but consistently improves alertness and fatigue, its effects on mental performance are largely restricted to improved attention or concentration. It has no consistent effect within other cognitive domains that are important to sporting performance, including working memory, executive function and long-term memory. Although caffeine's central nervous system effects are often attributed to blockade of the receptors for the inhibitory neuromodulator adenosine, it also inhibits a number of enzymes involved both in neurotransmission and in cellular homeostasis and signal propagation. Furthermore, it modulates the pharmacokinetics of other endogenous and exogenous bioactive molecules, in part via interactions with shared cytochrome P450 enzymes. Caffeine therefore enjoys interactive relationships with a wide range of bioactive medicinal and dietary compounds, potentially broadening, increasing, decreasing, or modulating the time course of their functional effects, or vice versa. This narrative review explores the mechanisms of action and efficacy of caffeine and the potential for combinations of caffeine and other dietary compounds to exert psychological effects in excess of those expected following caffeine alone. The review focusses on, and indeed restricted its untargeted search to, the most commonly consumed sources of caffeine: products derived from caffeine-synthesising plants that give us tea (Camellia sinensis), coffee (Coffea genus), cocoa (Theabroma cacao) and guaraná (Paullinia cupana), plus multi-component energy drinks and shots. This literature suggests relevant benefits to mental performance that exceed those associated with caffeine for multi-ingredient energy drinks/shots and several low-caffeine extracts, including high-flavanol cocoa and guarana. However, there is a general lack of research conducted in such a way as to disentangle the relative contributions of the component parts of these products.

Quantification of Cardiotonic Steroids Potentially Regulated by Paraoxonase 3 in a Rat Model of Chronic Kidney Disease Using UHPLC-Orbitrap-MS.

Endogenous cardiotonic steroids (CTSs), such as telocinobufagin (TCB) and marinobufagin (MBG) contain a lactone moiety critical to their binding and signaling through the Na+/K+-ATPase. Their concentrations elevate in response to sodium intake and under volume-expanded conditions. Paraoxonase 3 (PON3) is an enzyme that can hydrolyze lactone substrates. Here, we examine the role of PON3 in regulating CTS levels in a rat model of chronic kidney diseases (CKD). TCB and MBG were extracted from rat urine samples, and the analyses were carried out using ultra-high pressure liquid chromatography−Orbitrap-mass spectrometry (UHPLC-Orbitrap-MS). Ten-week-old Dahl salt-sensitive wild type (SS-WT) and Dahl salt-sensitive PON3 knockout (SS-PON3 KO) rats were maintained on a high-salt diet (8% NaCl) for 8 weeks to initiate salt-sensitive hypertensive renal disease characteristic of this model. CTS extraction recovery from urine >80% was achieved. For animals maintained on a normal chow diet, the baseline amount of TCB excreted in 24 h urine of SS-PON3 KO rats (6.08 ± 1.47 ng/24 h; or 15.09 ± 3.25 pmol) was significantly higher than for SS-WT rats (1.48 ± 0.69 ng/24 h; or 3.67 ± 1.54 pmol, p < 0.05). Similarly, for the same animals, the amount of excreted MBG was higher in the urine of SS-PON3 KO rats (4.74 ± 1.30 ng/24 h versus 1.03 ± 0.25 ng/24 h in SS-WT; or 11.83 ± 2.91 pmol versus 2.57 ± 0.56 pmol in SS-WT, p < 0.05). For animals on a high-salt diet, the SS-PON3 KO rats had significantly increased levels of TCB (714.52 ± 79.46 ng/24 h; or 1774.85 ± 175.55 pmol) compared to SS-WT control (343.84 ± 157.54 ng/24 h; or 854.09 ± 350.02 pmol, p < 0.05), and comparatively higher levels of MBG were measured for SS-PON3 KO (225.55 ± 82.61 ng/24 h; or 563.19 ± 184.5 pmol) versus SS-WT (157.56 ± 85.53 ng/24 h; or 393.43 ± 191.01 pmol, p > 0.05) rats. These findings suggest that the presence and absence of PON3 dramatically affect the level of endogenous CTSs, indicating its potential role in CTS regulation.

Prognosis of Distant Metastatic Sites in Anterior Skull Base Malignancies.

Objective This study aimed to provide information regarding the prognosis of patients presenting with metastatic anterior skull base malignancies based upon histology and site of distant metastasis (DM). Patients and Methods The National Cancer Database was queried for patients with anterior skull base malignant neoplasms with DM. Outcomes Prognosis was compared between site of DM and tumor histologies. A multivariable Cox proportional hazards model was used to identify prognostic factors for overall survival (OS). Results A total of 481 patients were identified. Lung was the most common site of DM (24.9%), followed by bone (22.2%), liver (5.6%), and brain (2.5%). Lung was the most common site for squamous cell carcinoma (SCCa) (28.3%), melanoma (37.7%), and adenoid cystic carcinoma (ACC; 31.4%). The median survival for patients presenting with metastatic disease regardless of tumor histology was 9.0 months (95% confidence interval [CI]: 8.2-10.3), and patients with metastasis to the liver had the best median survival at 15.5 months (95% CI: 10.5-25.6). The median survivals for the most common histologies, SCCa, melanoma, and ACC were 8.2 months (95% CI: 5.5-10.2), 10.5 months (95% CI: 8.7-14.1), and 15.0 months (95% CI: 11.1-61.1), respectively. Multivariable analysis demonstrated worse overall survival (OS) for older patients, higher Charlson-Deyo comorbidity scores, and tumors with higher grade and T stage. Compared with metastasis to bone, lung metastasis had better OS on multivariable analysis (hazard ratio [HR]: 0.70, 95% CI: 0.51-97). Adenoid cystic carcinoma had improved OS compared with SCCa (HR: 0.62, 95% CI: 0.39-99). Conclusion Tumor histology, metastatic sites, and several disease factors affected prognosis in anterior skull base malignancies with DM.

Odontogenic Sinusitis is a Common Cause of Operative Extra-Sinus Infectious Complications.

BACKGROUND: Orbital, intracranial, and osseous extra-sinus complications can arise from bacterial or fungal sinusitis. Odontogenic sinusitis (ODS) can cause extra-sinus complications, but its prevalence remains poorly characterized. OBJECTIVE: To determine the frequency of ODS as a cause of operative extra-sinus infectious complications and describe clinical features of all complicated sinusitis cases. METHODS: A multi-institutional retrospective review was performed on all operative sinusitis-related extra-sinus complications from 2011 to 2020. ODS was diagnosed by sinus computed tomography (CT) and dental evaluations when available. Demographics, complication types, sinusitis etiologies, and various clinical features were analyzed. RESULTS: Forty-five patients were included (mean age 55.5 years, 56% male). Of the extra-sinus complications, 40% were orbital only, 22% intracranial only, 13% osseous only, and 25% involved combined complications. The 2 most common causes of extra-sinus complications were ODS (40%) and mucopyocele (27%). When invasive fungal etiologies were excluded, and only unilateral maxillary opacification on CT was considered, nearly 60% of extra-sinus complications were due to ODS. Unilateral maxillary sinus opacification on CT was present in 100% of complicated ODS compared to 44% of nonodontogenic cases, and oral anaerobes were only identified in ODS cases. No complicated ODS patients underwent dental interventions during hospitalization. CONCLUSION: ODS was the most common cause of operative extra-sinus infectious complications. Clinicians should consider ODS high on the differential diagnosis of all patients presenting with complicated sinusitis, especially when sinusitis is unilateral and invasive fungal infection is not suspected.

Radioactive Iodine for the Treatment of Subclinical Thyrotoxicosis Grade 1 and 2: Outcome of up to 18-Year Follow Up.

Background: Subclinical thyrotoxicosis (SCT) is associated with significant morbidity and mortality, specifically increased risk of atrial fibrillation and cardiovascular death. The management is ill-defined due to the scarcity of randomised controlled studies. Some clinicians recommend radioiodine (RAI) treatment however its long-term outcome is unknown. Therefore, further data is needed to provide robust evidence-based guidelines. Methods: A prospective, single-protocol analysis of the outcome of SCT patients (Grade 1; 0.1-0.4 mIU/L and Grade 2; <0.1 mIU/L) treated with mean dose of 427 MBq of I131, followed up for up to 18 years. Thyroid function tests were measured at 4-6 weeks, 3-, 6-, and 12-months post-RAI, and annually thereafter. Cure was defined as achieving a euthyroid/hypothyroid state. Results: Seventy-eight patients with a median age of 68 years (range 36-84) and varying aetiology [55 toxic multinodular goitre (TMNG), 10 toxic nodule (TN) and 13 Graves' disease (GD)] were followed up for a median period of 7.5 years (range 1-18). The cure rate was 100%. The rates of hypothyroidism in TMNG, TN and GD were 23.6%, 30% and 38.5% respectively. The median time to hypothyroidism was 6 and 12 months in GD and TMNG/TN respectively. No differences in outcome between Grade 1 versus Grade 2 were observed. Conclusion: RAI using single mean dose of 427 MBq is effective and safe, irrespective of aetiology or grade of TSH suppression. GD patients become hypothyroid within the first year, whilst TMNG/TN for up to 9-years. Thus after 12 months of follow up, annual thyroid function monitoring is advised.

A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease.

Paraoxonases (PONs) are a family of hydrolytic enzymes consisting of three members, PON1, PON2, and PON3, located on human chromosome 7. Identifying the physiological substrates of these enzymes is necessary for the elucidation of their biological roles and to establish their applications in the biomedical field. PON substrates are classified as organophosphates, aryl esters, and lactones based on their structure. While the established native physiological activity of PONs is its lactonase activity, the enzymes' exact physiological substrates continue to be elucidated. All three PONs have antioxidant potential and play an important anti-atherosclerotic role in several diseases including cardiovascular diseases. PON3 is the last member of the family to be discovered and is also the least studied of the three genes. Unlike the other isoforms that have been reviewed extensively, there is a paucity of knowledge regarding PON3. Thus, the current review focuses on PON3 and summarizes the PON substrates, specific activities, kinetic parameters, and their association with cardiovascular as well as other diseases such as HIV and cancer.

Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma.

BACKGROUND: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma. METHODS: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors. RESULTS: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation). CONCLUSIONS: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.

Acute cognitive performance and mood effects of coffee berry and apple extracts: A randomised, double blind, placebo controlled crossover study in healthy humans.

Background: Polyphenols from coffee berry (chlorogenic acid) and apple (flavanol) have been shown to improve mood and increase cerebral blood flow in healthy humans. These effects may underpin the cognitive effects of polyphenols seen previously.Objective: The aim of the present paper was to extend previous research by investigating the effects of coffee berry at high and low doses when combined with apple extract on cognitive performance and mood.Design: This randomised, double-blind, placebo controlled, crossover trial included 46 healthy males and females,18-49 years of age (mean age 23 years),consuming: 1100 mg coffee berry extract, 1100 mg coffee berry extract plus 275 mg apple extract, 100 mg coffee berry extract plus 275 mg apple extract or placebo on 4 separate occasions, completing cognitive and mood assessments pre-dose and then again at 1-, 3- and 6 hrs post-dose.Results: Analysis revealed a consistent pattern of alerting effects following 1100 mg coffee berry extract. Limited effects on cognitive function were observed. Specifically, faster peg and ball performance (executive function) was observed following 1100 mg coffee berry plus apple extract and accuracy on the Rapid Visual Information Processing (RVIP) task increased on the third of four repetitions following 1100 mg coffee berry alone. Interestingly, more false alarms on RVIP were observed following the same intervention.Conclusions: In line with previous findings, 1100 mg coffee berry engendered increased arousal. The absence of effects on mood when an apple extract was added, and the potential for the low dose of caffeine within the coffee berry to act synergistically with polyphenols, raise interesting future avenues of research.Abbreviations: Cognitive demand battery (CDB), Profile Of Mood States (POMS), Visual Analogue Scale (VAS), Rapid Visual Information Processing (RVIP).

Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear. OBJECTIVE: We compared the effects of mAbs and aspirin desensitization (ASA-D) for treatment of CRSwNP. METHODS: We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US Food and Drug Administration, and the European Medicines Agency databases from inception to August 4, 2021, for randomized controlled trials comparing the effects of mAbs and ASA-D for CRSwNP. We conducted network meta-analysis of sinusitis symptoms, heath-related quality of life, rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence. PROSPERO CRD42020177334. RESULTS: Twenty-nine randomized controlled trials evaluating 8 treatments (n = 3461) were included in the network meta-analysis. Compared to placebo, moderate to high certainty evidence showed that health-related quality of life (SNOT-22) improved with dupilumab (mean difference [MD] -19.91 [95% confidence interval (CI) -22.50, -17.32]), omalizumab (MD -16.09 [95% CI -19.88, -12.30]), mepolizumab (MD -12.89 [95% CI -16.58, -9.19], ASA-D (MD -10.61 [95% CI -14.51, -6.71]), and benralizumab (MD -7.68 [95% CI -12.09, -3.27]). The risk of rescue nasal polyp surgery likely decreased with dupilumab (risk difference [RD] -16.35% [95% CI -18.13, -13.48]), omalizumab (RD -7.40% [95% CI -11.04, -2.43]), mepolizumab (RD -12.33% [95% CI -15.56, -7.22]), and ASA-D (RD -16.00% [95% CI -19.79, 0.21]; all moderate certainty). Comparisons among agents show with moderate to high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2 of 7, mepolizumab for 1 of 7, and ASA-D for 1 of 7. CONCLUSIONS: Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents; dupilumab uniquely ranks among the most beneficial for all outcomes studied.