Needs assessment for direct ophthalmoscopy training in neurology residency.

BACKGROUND: Assessment of the ocular fundus, traditionally by direct ophthalmoscopy (DO), is essential to evaluate many neurologic diseases. However, the status of DO training in neurology residencies is unknown. We conducted a needs assessment to determine current attitudes, curricula, and gaps in DO training. METHODS: A survey was developed and administered to residents and program directors (PDs) at ACGME accredited neurology residencies in the United States. The survey assessed factors such as current DO curricula, perceived importance of DO, confidence of skills, and need for improvement. Data analysis was performed using the Mann Whitney U test and Fisher Exact Test. RESULTS: Nineteen PDs (11.6%) and 74 (41.1%) residents responded to the survey. 97.1% of residents and 100.0% of PDs believe DO is an important skill to learn. 29.4% of PDs expected graduating residents to have completed > 10 supervised DO exams, while 0.0% of graduating fourth year residents reported doing so (p = 0.03). 35.7% of graduating residents had never correctly identified an abnormal finding on DO. The number of times residents practiced DO unsupervised correlated with increasing confidence in all components of the DO exam (p < 0.05). Residents who felt their program emphasized DO were more likely to perform DO at least once a week compared to residents who did not perceive program emphasis (61.9% vs. 35.0%, p = 0.02) and were more confident in DO (p < 0.05). 66.7% of residents and 42.1% of PDs were not satisfied with current levels of DO training. 96.7% of residents and 78.9% of PDs felt it was important to improve curriculum for DO training. Supervised practice and practice skills sessions were identified as the most helpful interventions to improve DO training. CONCLUSIONS: The vast majority of neurology PDs and residents believe DO is an important skill to learn, are unsatisfied with the current level of DO training, and advocate for improvement in DO curricula. Current DO curricula have limited formal didactic training and supervised practice. The bulk of DO learning occurs through unsupervised practice, which is influenced by motivational factors such as perceived residency emphasis on DO learning.

Distribution of Macrolide Resistant Mycoplasma genitalium in Urogenital Tract Specimens From Women Enrolled in a US Clinical Study Cohort.

BACKGROUND: This study evaluated the distribution of macrolide-resistant Mycoplasma genitalium in multiple urogenital specimens collected from women enrolled in a prospective multicenter US clinical study. METHODS: Four female urogenital specimens (vaginal swab, urine, endocervical swab, ectocervical brush/spatula) collected from each subject were tested using a transcription-mediated amplification (TMA) assay for M. genitalium. TMA-positive specimens were evaluated by reverse transcription-polymerase chain reaction and bidirectional Sanger sequencing of M. genitalium 23S rRNA to identify the presence of macrolide-resistance-mediating mutations (MRMs) at base positions 2058/2059. RESULTS: Of 140 women with ≥1 TMA-positive specimens, 128 (91.4%) yielded M. genitalium 23S rRNA sequence. MRMs were found in 52% of vaginal specimens, 46.3% of urine specimens, 37.8% of endocervical specimens, and 46% of ectocervical specimens. There were 44 unique specimen type/sequence phenotype combinations of M. genitalium infection. Most (81; 63.3%) women had single specimen-sequence phenotype (macrolide-susceptible, MRM, or both) infections, while 24 (18.8%) women had multiple specimen-sequence phenotype concordant infections, and 23 (17.9%) women had multiple specimen-sequence phenotype discordant infections. The sensitivity for any single specimen type to detect overall urogenital tract macrolide-resistant M. genitalium infection status was 96.3% for vaginal swab samples, 82.6% for urine samples, 70.8% for endocervical swab samples, and 82.1% for ectocervical brush/spatula liquid Pap samples. CONCLUSIONS: The distribution of M. genitalium infections in female urogenital tract specimens is highly complex, with multiple phenotypic combinations of the organism infecting a significant proportion of women at different anatomic specimen collection sites. Vaginal swab sampling yielded the highest sensitivity for identifying women with macrolide-resistant M. genitalium urogenital tract infections.

Relationship of blood thiamine pyrophosphate to plasma phosphate and the response to enteral nutrition plus co-administration of intravenous thiamine during critical illness.

BACKGROUND: Hypovitamin B1 occurs frequently during critical illness but is challenging to predict or rapidly diagnose. The aim of this study was to evaluate whether plasma phosphate concentrations predict hypovitamin B1, enteral nutrition prevents hypovitamin B1 and intravenous thiamine supplementation achieves supraphysiological concentrations in critically ill patients. METHODS: Thirty-two enterally fed critically ill patients, with a plasma phosphate concentration ≤0.65 mmol/L, formed a nested cohort within a larger randomised clinical trial. Patients were assigned to receive intravenous thiamine (200 mg) twice daily, and controls were not administered intravenous thiamine. Thiamine pyrophosphate concentrations were measured at four time points (pre- and post-infusion and 4- and 6-h post-infusion) on days 1 and 3 in those allocated to thiamine and once in the control group. RESULTS: Baseline thiamine pyrophosphate concentrations were similar (intervention 88 [67, 93] vs. control 89 [62, 110] nmol/L, p = 0.49). Eight (25%) patients had hypovitamin B1 (intervention 3 vs. control 5), with two patients in the control group remaining insufficient at day 3. There was no association between baseline phosphate and thiamine pyrophosphate concentrations. Intravenous thiamine achieved supraphysiological concentrations 6 h post first infusion, with concentrations increasing to day 3. In the control group, thiamine pyrophosphate concentrations were not statistically different between baseline and day 3 (mean change: 8.6 [-6.0, 23.1] nmol/L, p = 0.25). CONCLUSIONS: Phosphate concentrations did not predict hypovitamin B1, which was observed in 25% of the participants. Enteral nutrition alone prevented the development of new hypovitamin B1. Administration of a single 200-mg dose of intravenous thiamine achieved supraphysiological concentrations of thiamine pyrophosphate, with repeated dosing sustaining this effect.

DNA methylation and miRNA expression in colon adenomas compared with matched normal colon mucosa and carcinomas.

Dysregulation of DNA methylation patterns and non-coding RNA, including miRNAs, has been implicated in colon cancer, and these changes may occur early in the development of carcinoma. In this study, the role of epigenetics as early changes in colon tumorigenesis was examined through paired sample analysis of patient-matched normal, adenoma and carcinoma samples. Global methylation was assessed by genomic 5-methyl cytosine (5-mC) and long interspersed nuclear element-1 (LINE-1) promoter methylation by pyrosequencing. KRAS mutations were also assessed by pyrosequencing. Expression of miRNA, specifically, two microRNA genes-miR-200a and let-7c-was analysed using RT-qPCR. Differences in global methylation in adenomas were not observed, compared with normal tissue. However, LINE-1 methylation was decreased in adenomas (p = .056) and carcinomas (p = .011) compared with normal tissue. Expressions of miRNA, miR-200a and let-7c were significantly higher in adenomas than normal tissues (p = .008 and p = .045 respectively). Thus the significant changes in LINE-1 methylation and microRNA expression in precancerous lesions support an early role for epigenetic changes in the carcinogenic process. Epigenetic characteristics in adenomas may provide potential diagnostic and prognostic therapeutic targets early in cancer development at the adenoma stage.

Volumetric modulated arc therapy total body irradiation in pediatric and adolescent/young adult patients undergoing stem cell transplantation: Early outcomes and toxicities.

INTRODUCTION: Total body irradiation (TBI) is an important component of many conditioning regimens for hematopoietic stem cell transplantation (HSCT), most commonly used in pediatric and adolescent/young adult (AYA) patients. We aimed to evaluate outcomes and toxicities among pediatric and AYA patients treated with TBI utilizing volumetric modulated arc therapy total body irradiation (VMAT-TBI). METHODS: We reviewed pediatric and AYA patients treated with VMAT-TBI at our institution from 2019 to 2021. Data on patient and disease characteristics, treatment details, outcomes and toxicities were collected. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method. RESULTS: Among 38 patients, 16 (42.1%) were treated with myeloablative regimens and 22 (57.9%) with nonmyeloablative regimens. Median age was 7.2 years (range: 1-27) and median follow-up was 8.7 months (range: 1-21). Lungs Dmean was 7.3 ± 0.3 Gy for myeloablative regimens (range: 6.8-7.8). Kidneys were spared to average mean dose of 71.4 ± 4.8% of prescription dose. Gonadal sparing was achieved for patients treated for nonmalignant diseases to Dmean of 0.7 ± 0.1 Gy. No patient experienced primary graft failure; one (2.6%) experienced secondary graft failure. The most common grade 1-2 acute toxicities were nausea (68.4%) and fatigue (55.3%). Mucositis was the most common grade 3-4 acute toxicity, affecting 39.5% of patients. There were no cases of pneumonitis or nephrotoxicity attributable to TBI. CONCLUSION: VMAT-TBI offers increased ability to spare organs at risk in pediatric and AYA patients undergoing HSCT, with a favorable acute/subacute toxicity profile and excellent disease control.

Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65.

At least 120 non-olfactory G-protein-coupled receptors in the human genome are 'orphans' for which endogenous ligands are unknown, and many have no selective ligands, hindering the determination of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Using yeast-based screens against GPR68, here we identify the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. More than 3,000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators, many of which were confirmed in functional assays. One potent GPR68 modulator, ogerin, suppressed recall in fear conditioning in wild-type but not in GPR68-knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs.

Mindfulness-based psychological interventions for improving mental well-being in medical students and junior doctors.

BACKGROUND: Mindfulness interventions are increasingly popular as an approach to improve mental well-being. To date, no Cochrane Review examines the effectiveness of mindfulness in medical students and junior doctors. Thus, questions remain regarding the efficacy of mindfulness interventions as a preventative mechanism in this population, which is at high risk for poor mental health.  OBJECTIVES: To assess the effects of psychological interventions with a primary focus on mindfulness on the mental well-being and academic performance of medical students and junior doctors. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and five other databases (to October 2021) and conducted grey literature searches.  SELECTION CRITERIA: We included randomised controlled trials of mindfulness that involved medical students of any year level and junior doctors in postgraduate years one, two or three. We included any psychological intervention with a primary focus on teaching the fundamentals of mindfulness as a preventative intervention. Our primary outcomes were anxiety and depression, and our secondary outcomes included stress, burnout, academic performance, suicidal ideation and quality of life.  DATA COLLECTION AND ANALYSIS: We used standard methods as recommended by Cochrane, including Cochrane's risk of bias 2 tool (RoB2).  MAIN RESULTS: We included 10 studies involving 731 participants in quantitative analysis.  Compared with waiting-list control or no intervention, mindfulness interventions did not result in a substantial difference immediately post-intervention for anxiety (standardised mean difference (SMD) 0.09, 95% CI -0.33 to 0.52; P = 0.67, I2 = 57%; 4 studies, 255 participants; very low-certainty evidence). Converting the SMD back to the Depression, Anxiety and Stress Scale 21-item self-report questionnaire (DASS-21) showed an estimated effect size which is unlikely to be clinically important. Similarly, there was no substantial difference immediately post-intervention for depression (SMD 0.06, 95% CI -0.19 to 0.31; P = 0.62, I2 = 0%; 4 studies, 250 participants; low-certainty evidence). Converting the SMD back to DASS-21 showed an estimated effect size which is unlikely to be clinically important. No studies reported longer-term assessment of the impact of mindfulness interventions on these outcomes.  For the secondary outcomes, the meta-analysis showed a small, substantial difference immediately post-intervention for stress, favouring the mindfulness intervention (SMD -0.36, 95% CI -0.60 to -0.13; P < 0.05, I2 = 33%; 8 studies, 474 participants; low-certainty evidence); however, this difference is unlikely to be clinically important. The meta-analysis found no substantial difference immediately post-intervention for burnout (SMD -0.42, 95% CI -0.84 to 0.00; P = 0.05, I² = 0%; 3 studies, 91 participants; very low-certainty evidence). The meta-analysis found a small, substantial difference immediately post-intervention for academic performance (SMD -0.60, 95% CI -1.05 to -0.14; P < 0.05, I² = 0%; 2 studies, 79 participants; very low-certainty evidence); however, this difference is unlikely to be clinically important. Lastly, there was no substantial difference immediately post-intervention for quality of life (mean difference (MD) 0.02, 95% CI -0.28 to 0.32; 1 study, 167 participants; low-certainty evidence). There were no data available for three pre-specified outcomes of this review: deliberate self-harm, suicidal ideation and suicidal behaviour. We assessed the certainty of evidence to range from low to very low across all outcomes. Across most outcomes, we most frequently judged the risk of bias as having 'some concerns'. There were no studies with a low risk of bias across all domains.  AUTHORS' CONCLUSIONS: The effectiveness of mindfulness in our target population remains unconfirmed. There have been relatively few studies of mindfulness interventions for junior doctors and medical students. The available studies are small, and we have some concerns about their risk of bias. Thus, there is not much evidence on which to draw conclusions on effects of mindfulness interventions in this population. There was no evidence to determine the effects of mindfulness in the long term.

Acute stress-induced cortisol elevation during memory consolidation enhances pattern separation.

Stress is a potent modulator of brain function and particularly mnemonic processes. While chronic stress is associated with long-term deficits in memory, the effects of acute stress on mnemonic functions are less clear as previous reports have been inconsistent. Some studies suggest that cortisol, a stress hormone that modulates biological changes in response to stress, may enhance memory consolidation and impair memory retrieval. However, other studies report no effect of cortisol on either memory consolidation or retrieval. These discrepancies could be due to differences in the timing and sequencing of the experimental procedures or individual differences in participants' stress response. In the present study, we examined the effect of increased cortisol levels due to acute stress, induced by the Trier Social Stress Test (TSST), on a pattern separation memory task while differentiating the distinct stages of memory processing and controlling for the effects of diurnal variation. Sixty-nine young adults completed a 2-d study in which subjects either underwent the TSST immediately following the encoding part of the memory task, targeting memory consolidation, or immediately prior to the recognition part of the memory task on the second day, targeting memory retrieval. Control subjects completed the same study procedures but underwent a control version of the TSST that did not induce a stress response. Mnemonic discrimination of highly similar stimuli was enhanced by stress induced during consolidation with better discrimination showing a significant correlation with increased cortisol responses. Stress induced during memory retrieval showed no significant effect on memory performance. These findings suggest that stress induced changes in cortisol differentially affect the consolidation and retrieval stages of memory function.

Quantitative Ultra-Widefield Angiography and Diabetic Retinopathy Severity: An Assessment of Panretinal Leakage Index, Ischemic Index and Microaneurysm Count.

PURPOSE: To investigate the relationship between the diabetic retinopathy (DR) severity and quantitative ultra-widefield angiographic metrics, including leakage index, ischemic index, and microaneurysm count. DESIGN: Retrospective image analysis study. METHODS: Eyes with DR that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color photography were identified. All eyes were laser-naive and had not received any intravitreal pharmacotherapy within 6 months of UWFA. Each eye was graded for DR severity. Quantitative angiographic parameters were evaluated with a semiautomated analysis platform with expert reader correction, as needed. Angiographic parameters included panretinal leakage index, ischemic index, and microaneurysm count. Clinical characteristics analyzed included age, gender, race, hemoglobin A1C level, hypertension, systolic blood pressure, diastolic blood pressure, and smoking history. MAIN OUTCOME MEASURES: Association of DR severity with panretinal leakage index, ischemic index, and microaneurysm count. RESULTS: Three hundred thirty-nine eyes were included with mean age of 62±13 years. Forty-two percent of eyes were from women and 57.5% were from men. Distribution of DR severity was as follows: mild NPDR in 11.2%, moderate NPDR in 23.9%, severe NPDR in 40.1%, and PDR with 24.8%. Panretinal leakage index [mild NPDR (mean = 0.51%), moderate NPDR mean = 1.20%, severe NPDR (mean = 2.75%), and PDR (mean = 5.84%); P<2×10-16], panretinal ischemic index [mild NPDR (mean = 0.95%, moderate NPDR (mean = 1.37%), severe NPDR (mean = 2.80%), and PDR (mean = 9.53%); P<2×10-16], and panretinal microaneurysm count [mild NPDR (mean = 36), moderate NPDR (mean = 129), severe NPDR (mean = 203), and PDR (mean = 254); P<5×10-7] were strongly associated with DR severity. Multivariate analysis demonstrated that ischemic index and leakage index were the parameters associated most strongly with level of DR severity. CONCLUSIONS: Panretinal leakage index, panretinal ischemic index, and panretinal microaneurysm count are associated with DR severity. Additional research is needed to understand the clinical implications of these parameters related to progression risk, prognosis, and implications for therapeutic response.

Hedgehog-induced phosphorylation by CK1 sustains the activity of Ci/Gli activator.

Hedgehog (Hh) signaling governs many developmental processes by regulating the balance between the repressor (Ci(R)/Gli(R)) and activator (Ci(A)/Gli(A)) forms of Cubitus interruptus (Ci)/glioma-associated oncogene homolog (Gli) transcription factors. Although much is known about how Ci(R)/Gli(R) is controlled, the regulation of Ci(A)/Gli(A) remains poorly understood. Here we demonstrate that Casein kinase 1 (CK1) sustains Hh signaling downstream of Costal2 and Suppressor of fused (Sufu) by protecting Ci(A) from premature degradation. We show that Hh stimulates Ci phosphorylation by CK1 at multiple Ser/Thr-rich degrons to inhibit its recognition by the Hh-induced MATH and BTB domain containing protein (HIB), a substrate receptor for the Cullin 3 family of E3 ubiquitin ligases. In Hh-receiving cells, reduction of CK1 activity accelerated HIB-mediated degradation of Ci(A), leading to premature loss of pathway activity. We also provide evidence that Gli(A) is regulated by CK1 in a similar fashion and that CK1 acts downstream of Sufu to promote Sonic hedgehog signaling. Taken together, our study not only reveals an unanticipated and conserved mechanism by which phosphorylation of Ci/Gli positively regulates Hh signaling but also provides the first evidence, to our knowledge, that substrate recognition by the Cullin 3 family of E3 ubiquitin ligases is negatively regulated by a kinase.

Mycoplasma genitalium Prevalence, Coinfection, and Macrolide Antibiotic Resistance Frequency in a Multicenter Clinical Study Cohort in the United States.

The prevalence rates of Mycoplasma genitalium infections and coinfections with other sexually transmitted organisms and the frequency of a macrolide antibiotic resistance phenotype were determined in urogenital specimens collected from female and male subjects enrolled in a multicenter clinical study in the United States. Specimens from 946 subjects seeking care from seven geographically diverse clinical sites were tested for M. genitalium and for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis Sequencing was used to assess macrolide antibiotic resistance among M. genitalium-positive subjects. M. genitalium prevalence rates were 16.1% for females and 17.2% for males. Significant risk factors for M. genitalium infections were black race, younger age, non-Hispanic ethnicity, and female symptomatic status. Female M. genitalium infections were significantly more prevalent than C. trachomatis and N. gonorrhoeae infections, while the M. genitalium infection rate in males was significantly higher than the N. gonorrhoeae and T. vaginalis infection rates. The macrolide-resistant phenotype was found in 50.8% of females and 42% of males. These results show a high prevalence of M. genitalium single infections, a lower prevalence of coinfections with other sexually transmitted organisms, and high rates of macrolide antibiotic resistance in a diverse sample of subjects seeking care across a wide geographic area of the United States.

Effect of single-dose albendazole and vitamin A supplementation on the iron status of pre-school children in Sichuan, China.

The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 µg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4·4 (sd 0·7) years and 50·5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (P<0·05). Moreover, the proportion of vitamin A deficiency, marginal vitamin A deficiency and Fe deficiency among children in group 3 were markedly lower compared with children in groups 1 and 2 (P<0·05). Albendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status.

Vision-related quality of life and psychological status in Chinese women with Sjogren's syndrome dry eye: a case-control study.

BACKGROUND: Sjogren's syndrome dry eye (SSDE) mainly affects middle-aged women and can negatively affect women's psychological and social functioning. However, little is known about the correlation between vision-related quality of life (VR-QoL) and psychological status for women with SSDE. We therefore examined VR-QoL and psychological status in two groups of Chinese women: an SSDE group and a non-SSDE group. We also explored the associations between VR-QoL scores, sociodemographic measures, ophthalmologic parameters, and psychological status in women with SSDE. METHODS: The case-control study recruited 30 female outpatients with SSDE and 30 without SSDE from the Eye and Ear, Nose, and Throat (ENT) Hospital of Fudan University. Demographic and ophthalmologic data were collected from all participants. Ophthalmologic examinations included best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS), tear break-up time (TBUT) and Schirmer test. Data collected using the National Eye Institute's Visual Function Questionnaire (NEI-VFQ) and Ocular Surface Disease Index (OSDI) survey instruments were analyzed to identify potential differences in VR-QoL between the SSDE group and the non-SSDE group. We also used the Zung Self-Rating Anxiety and Self-Rating Depression Scales (SAS and SDS) to determine psychological status in both groups. RESULTS: The SSDE group scored significantly lower than the non-SSDE group on the NEI-VFQ subscales of general health, general vision, and long-distance vision activities (all p < 0.05). The SSDE group achieved a significantly higher ocular symptoms score compared with the control group (p = 0.0256). The SAS and SDS scores of the SSDE group were significantly higher than the non-SSDE group (p = 0.0072 and 0.0162, respectively). The prevalence of anxiety and depression in the SSDE group was significantly higher than the non-SSDE group (p = 0.0240 and 0.0200, respectively). Nine of twelve NEI-VFQ subscales were negatively correlated with SAS/SDS scores (all p values were <0.05). The exceptions were social function, color vision and peripheral vision. The composite OSDI score and its three subscale scores for the women in the SSDE group were all positively correlated with overall SAS/SDS scores (all p values were <0.05). CONCLUSIONS: Both VR-QoL and psychological status were significantly worse in SSDE group than in the non-SSDE group. The VR-QoL of women with SSDE had a negative correlation with their anxiety and depression levels.

An updated review of worldwide levels of docosahexaenoic and arachidonic acid in human breast milk by region.

OBJECTIVE: We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status. DESIGN: Descriptive review conducted on English publications reporting breast-milk DHA and AA levels. SETTING: We systematically searched and identified eligible literature in PubMed from January 1980 to July 2015. Data on breast-milk DHA and AA levels from women who had given birth to term infants were included. SUBJECTS: Seventy-eight studies from forty-one countries were included with 4163 breast-milk samples of 3746 individuals. RESULTS: Worldwide mean levels of DHA and AA in breast milk were 0·37 (sd 0·11) % and 0·55 (sd 0·14) % of total fatty acids, respectively. The breast-milk DHA levels from women with accessibility to marine foods were significantly higher than those from women without accessibility (0·35 (sd 0·20) % v. 0·25 (sd 0·14) %, P<0·05). Data from the Asian region showed the highest DHA concentration but much lower AA concentration in breast milk compared with all other regions, independent of accessibility to marine foods. Comparison was made among Canada, Poland and Japan - three typical countries (each with sample size of more than 100 women) from different regions but all with high income and similar accessibility to fish/marine foods. CONCLUSIONS: The current review provides an update on worldwide variation in breast-milk DHA and AA levels and underlines the need for future population- or region-specific investigations.

Suppression of Chlorantraniliprole Sorption on Biochar in Soil-Biochar Systems.

The sorption behavior of chlorantraniliprole (CAP) by biochar and effect of soil extracts on sorptivity in soil-biochar systems were examined. The results showed that biochar amendment could enhance the sorption of CAP in soils. The values of K F increased significantly when the soils were amended with 0.5 % BC850, which were from 1.54 to 196.5. The indigenous sorptivity of biochar was suppressed after it was applied to the soils. The degree of biochar sorptivity attenuation in different soil-biochar systems varied with the properties of soil water soluble matters. Sorption of CAP by biochar from the five soil extracts was found to be lower than that from a CaCl2 solution. The calculated K d values at C w of 0.01 mg kg(-1) for biochar sorption of CAP from CaCl2 solution were 21.4-26.6 times of that from soil extracts. Aging of biochar in soil extract reduced CAP sorption by up to 85 %.

Unilateral progressive keratoconus associated with ipsilateral craniofacial fibrous dysplasia treated with corneal cross-linking.

Purpose: The purpose of this study is to describe a case of unilateral keratoconus associated with ipsilateral craniofacial fibrous dysplasia and its subsequent management with corneal collagen cross-linking. Observations: This is an interventional case report of a 16-year-old male with a history of polyostotic fibrous dysplasia of the left frontal bone and orbital roof status post partial resection six years prior who presented to the pediatric ophthalmology clinic with progressively blurry vision in the left eye. Refraction in this eye revealed an increase in cylinder by > 3D from his last refraction two years prior. Pentacam corneal tomography confirmed the diagnosis of keratoconus in the left eye. The patient underwent corneal collagen cross-linking in the affected eye. Postoperatively, he experienced marked improvement in corrected visual acuity with scleral contact lenses and maintained stable astigmatism and keratometry values on Pentacam corneal tomography at his most recent visit 12 months postoperatively. Conclusions: While it is otherwise felt to be a bilateral disease, unilateral keratoconus may present in the context of ipsilateral orbital pathology. Corneal collagen cross-linking may be used to successfully prevent keratoconus progression in the setting of stable orbital pathology.

Long-term Outcomes of Diffuse or Recurrent Tenosynovial Giant Cell Tumor Treated with Postoperative External Beam Radiation Therapy.

PURPOSE: Tenosynovial giant cell tumor (TGCT) is a rare proliferative disorder of synovial membrane that previously was known as pigmented villonodular synovitis. Primary treatment involves surgical resection; however, complete removal of all disease involvement is difficult to achieve. Radiation may be useful to reduce the risk of recurrence. We report and update our institutional experience treating diffuse and recurrent TGCT with postsurgical external beam radiation therapy. METHODS AND MATERIALS: We performed a retrospective chart review of 30 patients with TGCT from 2003 to 2019 treated with radiation therapy. Each patient was evaluated for demographics, radiation treatment parameters, surgical management, complications, and outcome. RESULTS: With mean follow-up of 82 months (range, 3-211), 24 patients (80%) who underwent surgery followed by radiation therapy did not experience any further relapse, and all 30 patients achieved local control (100%) with additional salvage therapy after radiation therapy. The most common site of disease was the knee (n = 22, 73%), followed by the ankle (n = 5, 16%) and the hand (n = 3, 10%). Seven patients (24%) presented at time of initial diagnosis and 23 (76%) presented with recurrent disease after surgical resection, with an average of 2.6 surgical procedures before radiation therapy. After resection, 18 of 30 patients (67%) demonstrated residual TGCT by imaging. The median radiation therapy dose delivered was 36 Gy (range, 34-36 Gy) in 1.8 to 2.5 Gy/fractions for 4 weeks. In the assessment of posttreatment joint function, 26 sites (86%) exhibited excellent or good function, 2 (7%) fair, and 2 poor (7%) as determined by our scoring system. There were no cases of radiation-associated malignancy. CONCLUSIONS: Among patients with diffuse or recurrent TGCT, postsurgical external beam radiation therapy provided excellent local control and good functional status, with minimal treatment-related complications. Postsurgical radiation therapy is a well-tolerated noninvasive treatment that should be considered after maximal cytoreductive resection to prevent disease progression and recurrence.

Effect of Testicular Boost in Children With Leukemia Receiving Total Body Irradiation and Stem Cell Transplant: A Single-Institution Experience.

Purpose: Children with leukemia who receive fractionated total body irradiation (fTBI) with 12 to 13.2 Gy as part of conditioning for hematopoietic stem cell transplant are frequently treated with an additional 4 Gy testicular boost to reduce the risk of testicular relapse. While institutional practices vary, limited data exists regarding whether the 4-Gy testicular boost reduces the risk of relapse and whether it causes toxicity beyond that imparted by TBI. This study compared the survival and endocrine outcomes among the patients who were treated with and without a testicular boost as part of fTBI from 1990 to 2019 at our center. Methods and Materials: We retrospectively reviewed charts of male children with leukemia treated with fTBI as part of a conditioning regimen for stem cell transplant from 1990 to 2019. Reported outcomes included progression-free survival, testicular relapse rate, and overall survival. Gonadal dysfunction and fertility were assessed by comparing the rate of abnormally low testosterone or high luteinizing hormone or follicular stimulating hormone, number of offspring, fertility service use, and abnormal sperm count in the subsequent follow-up period between the testicular boost and nonboost subset. Results: Ninety-three male patients (63 acute lymphoblastic leukemia, 30 acute myeloid leukemia) with a median age of 9 years (range, 1-22) and follow-up of 3.3 years were included. In addition to 12- to 13.2-Gy fTBI, 51 male patients (54%) received a testicular boost to 4 Gy. There was 1 testicular relapse in the boost subset and none in the nonboost subset. Five-year progression-free survival for the boost and nonboost subset was 74% and 66%, respectively (P = .31). On multivariable analysis, boost was not associated with improved relapse-free survival or overall survival. More patients in the boost subset (35 of 51, 69%) had abnormal serum gonadal blood work compared with the nonboost subset (18 of 42, 43%) (P = .03). Conclusions: Omission of testicular boost may be associated with comparable oncologic but improved gonadal endocrine outcomes and should be further studied.

EXT418, a novel long-acting ghrelin, mitigates Lewis lung carcinoma induced cachexia in mice.

BACKGROUND: Ghrelin is a potential therapy for cachexia due to its orexigenic properties and anabolic effects on muscle and fat. However, its clinical use is limited by the short half-life of active (acylated) ghrelin (~11 min in humans). EXT418 is a novel long-acting, constitutively active ghrelin analog created by covalently linking it to a vitamin D derivative. Here, we evaluated the effects and mechanisms of action of EXT418 on Lewis lung carcinoma (LLC)-induced cachexia in mice. METHODS: Male C57BL/6J mice (5- to 7-month-old) were implanted with 1 × 106 heat-killed (HK) or live LLC cells. When the tumour was palpable, mice were injected with vehicle (T + V) or EXT418 daily (T + 418 Daily, 0.25 mg/kg/day) or every other day (T + 418 EOD, 0.5 mg/kg/EOD) for up to 14 days, whereas HK-treated mice were given vehicle (HK + V). Subsets of T + 418 Daily or EOD-treated mice were pair-fed to the T + V group. Body composition and grip strength were evaluated before tumour implantation and at the end of the experiment. Molecular markers were probed in muscles upon termination. RESULTS: In tumour-bearing mice, administration of EXT418 daily or EOD partially prevented weight loss (T + V vs. T + 418 Daily, P = 0.030; and vs. T + 418 EOD, P = 0.020). Similar effects were observed in whole body fat and lean body mass. Grip strength in tumour-bearing mice was improved by EXT418 daily (P = 0.010) or EOD (P = 0.008) administration compared with vehicle-treated mice. These effects of EXT418 on weight and grip strength were partially independent of food intake. EXT418 daily administration also improved type IIA (P = 0.015), IIB (P = 0.037) and IIX (P = 0.050) fibre cross-sectional area (CSA) in tibialis anterior (TA) and EXT418 EOD improved CSA of IIB fibres in red gastrocnemius (GAS; P = 0.005). In skeletal muscles, tumour-induced increases in atrogenes Fbxo32 and Trim63 were ameliorated by EXT418 treatments (TA and GAS/plantaris, PL), which were independent of food intake. EXT418 administration decreased expression of the mitophagy marker Bnip3 (GAS/PL; P ≤ 0.010). Similar effects of EXT418 EOD were observed in p62 (GAS/PL; P = 0.039). In addition, EXT418 treatments ameliorated the tumour-induced elevation in muscle Il6 transcript levels (TA and GAS/PL), independently of food intake. Il-6 transcript levels in adipose tissue and circulating IL-10 were elevated in response to the tumour but these increases were not significant with EXT418 administration. Tumour mass was not altered by EXT418. CONCLUSIONS: EXT418 mitigates LLC-induced cachexia by attenuating skeletal muscle inflammation, proteolysis, and mitophagy, without affecting tumour mass and partially independent of food intake.