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TRPM3 encodes a transient receptor potential cation channel of the melastatin family, expressed in the central nervous system and in peripheral sensory neurons of the dorsal root ganglia. The recurrent substitution in TRPM3: c.2509G>A, p.(Val837Met) has been associated with syndromic intellectual disability and seizures. In this report, we present the clinical and molecular features of seven previously unreported individuals, identified by exome sequencing, with the recurrent p.(Val837Met) variant and global developmental delay. Other shared clinical features included congenital hypotonia, dysmorphic facial features (broad forehead, deep-set eyes, and down turned mouth), exotropia, and musculoskeletal issues (hip dysplasia, hip dislocation, scoliosis). Seizures were observed in two of seven individuals (febrile seizure in one and generalized tonic–clonic seizures with atonic drops in another), and epileptiform activity was observed in an additional two individuals. This report extends the number of affected individuals to 16 who are heterozygous for the de novo recurrent substitution p.(Val837Met). In contrast with the initial report, epilepsy was not a mandatory feature observed in this series. TRPM3 pathogenic variation should be considered in individuals with global developmental delays, moderate–severe intellectual disability with, or without, childhood-onset epilepsy.

Background The decision to initiate pharmacotherapy is integral in the care for pregnant women with gestational diabetes mellitus (GDM). We sought to compare pregnancy outcomes between two threshold percentages of elevated glucose values prior to initiation of pharmacotherapy for GDM. We hypothesized that a lower threshold at pharmacotherapy initiation will be associated with lower rates of adverse perinatal outcomes. Methods This was a retrospective cohort study of women with GDM delivering in a single tertiary care center. Pregnancy outcomes were compared using bivariable and multivariable analyses between women who started pharmacotherapy (insulin or oral hypoglycemic agent) after a failed trial of dietary modifications at two different ranges of elevated capillary blood glucose (CBG) values: Group 1 when 20–39% CBG values were above goal; Group 2 when ≥40% CBG values were above goal. The primary outcome was a composite GDM-associated neonatal adverse outcome that included: macrosomia, large for gestational age (LGA), shoulder dystocia, hypoglycemia, hyperbilirubinemia requiring phototherapy, respiratory distress syndrome, stillbirth, and neonatal demise. Secondary outcomes included cesarean delivery, preterm birth ( Results A total of 417 women were included in the study. In univariable analysis, the composite neonatal outcome was statistically significantly higher in Group 2 compared to Group 1 (47.9% vs. 31.4%, p = 0.001). In addition, rates of preterm birth (15.7% vs 7.4%, p = 0.011), NICU admission (11.7% vs 4.0%, p = 0.006), and LGA (21.2% vs 9.1% p = 0.001) were higher in Group 2. In contrast, higher rates of SGA were noted in Group 1 (8.0% vs. 2.9%, p = 0.019). There was no difference in cesarean section rates. These findings persisted in multivariable analysis after adjusting for confounding factors (composite neonatal outcome aOR = 0.50, 95%CI [0.31–0.78]). Conclusions Initiation of pharmacotherapy for GDM when 20–39% of CBG values are above goal, compared to ≥40%, was associated with decreased rates of adverse neonatal outcomes attributable to GDM. This was accompanied by higher rates of SGA among women receiving pharmacotherapy at the lower threshold. Additional studies are required to identify the optimal threshold of abnormal CBG values to initiate pharmacotherapy for GDM.

BACKGROUND: Multiple sclerosis (MS) is a disease involving demyelination of the central nervous system. Medication management in MS is a vital step in preventing further disease progression. OBJECTIVE: This article presents healthcare providers with an aide-mémoire in the form of a mnemonic to assist in the medication management of MS. METHODS: We explored recent guidelines, systematic reviews, and randomized controlled trials using PubMed, MEDLINE, and CINAHL to analyze the role and efficacy of pharmacotherapy in relapse prevention of MS. CONCLUSION: It is crucial to consider the classifications of MS and its pathophysiology to determine which medication produces the best results. Our proposed mnemonic can support a clinician's recall ability and assist in identifying the respective MS medication.

Introduction Calcinosis cutis is a condition characterized by pathologic calcium deposition into superficial dermal skin layers. It is often associated with an autoimmune disease. However, it may also occur after minor localized trauma and infection. Description of Problem We report a case of lumbar epidural placement of labor analgesia in a parturient with severe dystrophic calcinosis cutis without apparent complications. Clinical Solution We recommend fastidious optimization of epidural placement conditions for all patients who may be at high risk for neuraxial anesthesia, including consideration of ultrasound use, use of an experienced anesthesia provider for neuraxial placement, and placement in early labor. Additionally, judicious discussion of risks, benefits, and alternatives when obtaining informed consent is critical, ideally with the patient identified for a comprehensive visit in a preoperative obstetric anesthesia clinic before delivery.

We sought to assess parental support for varying standards that social media sites can employ to combat vaccine misinformation. Between July and August 2019, we conducted a web-based survey with a national sample of 1073 parents of adolescents and who use social media. The survey assessed support for ten standards about vaccine misinformation. Multivariable logistic regression assessed correlates of support. Overall, 61% of parents supported at least one standard. Support for each standard varied greatly (12-51%), with higher support for less restrictive standards. Parents more often supported standards if their child had already initiated human papillomavirus (HPV) vaccination, if they were non-Hispanic black or Hispanic, if they agreed that vaccine misinformation is harmful, or if they saw information on social media in favor of HPV vaccine (all p < .05). Our findings suggest favorable support for standards that social media sites can implement to combat vaccine misinformation.

Objectives Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine. Patients and methods Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored. Results 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of “Complete Response” than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of “No significant nausea” and “No nausea” during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment. Conclusion The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted., Highlights • Olanzapine is reported to reduce nausea and vomiting after highly emetogenic chemotherapy. • Reported studies are limited by heterogeneous populations receiving diverse cytotoxic regimes. • This study enrolled Chinese breast cancer patients undergoing doxorubicin/cyclophosphamide. • Adding olanzapine to aprepitant/ondansetron/dexamethasone is superior in controlling nausea and vomiting. • Baseline investigations shows a surprisingly high rate of glucose and lipids abnormalities.

ObjectivesThis is a prospective study evaluating NEPA in patients with breast cancer (the NEPA group), who received (neo)adjuvant AC chemotherapy (consisting of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2). The primary objectives were to assess the efficacy and safety of NEPA in controlling chemotherapy-induced nausea and vomiting (CINV). The secondary objectives were to compare CINV between the NEPA group and historical controls (the APR group) who received aprepitant in an earlier prospective randomised study.Patients and methods60 patients participated in the NEPA group; 62 were in the APR group. Eligibility criteria of both groups were similar, that is, Chinese patients with breast cancer who were treated with (neo)adjuvant AC. NEPA group received NEPA and dexamethasone; APR group received aprepitant, ondansetron and dexamethasone. Individuals filled in self-reported diary, visual analogue scale for nausea and Functional Living Index-Emesis questionnaire.ResultsWithin the NEPA group, 70.0%, 85.7% and 60.0%, respectively reported complete response in the acute, delayed and overall phases in cycle 1 AC. When compared with the historical APR group during cycle 1 AC, NEPA group achieved significantly higher rates of complete response, complete protection, total control, ‘no significant nausea’ and ‘no nausea’ in the delayed phase; similar findings were noted in the overall phase with significantly better quality of life. Superior efficacy of NEPA was maintained over multiple cycles. Both antiemetic regimens were well tolerated.ConclusionIn this study on Chinese patients with breast cancer who were uniformly receiving AC, NEPA was effective in controlling CINV.Trial registration numberNCT03386617.

We present a case of a 53-yr-old woman presenting with insidious shoulder pain and weakness. This case will go through the physical examination of the shoulder, a broad differential diagnosis, and analysis of appropriate imaging and tests to culminate in determining the final diagnosis. The objective of this clinical vignette was to highlight the importance of obtaining an extensive differential for shoulder pain and give readers a chance to critically analyze the case findings through electromyography interpretation, evaluating neurological signs and identifying key points in history taking. In addition, readers will also learn the evidence behind the available treatment options.

Objective We sought to identify patients at risk of incomplete transvaginal oocyte retrieval, develop a risk assessment formula to identify patients who would benefit from a transabdominal approach, and compare complication and pregnancy rates between these two approaches. Materials and Methods In this retrospective case control study in a private in vitro fertilization center, 95 cases of women undergoing transabdominal follicular aspiration for oocyte retrieval (15 transabdominal only and 80 transabdominal and vaginal combined) were compared with 278 controls of women undergoing the transvaginal aspiration only. Transabdominal oocyte retrieval was performed when one or more ovaries could not be retrieved via the transvaginal approach. Main study outcomes included need for transabdominal retrieval, pregnancy rates, and complications. Results A risk assessment scoring system was developed as follows: difficulty seeing ovaries on ultrasound (+4), history of pelvic surgery (+3), and body mass index of 30 kg/m 2 or greater (+2). With a cutoff score of 4 or greater, the overall sensitivity is 75%, specificity is 80%, positive predictive value is 57%, and negative predictive value is 90%. No statistically significant differences were found for pregnancy rates or complications. Conclusion The transabdominal approach is an alternative option that would increase the total number of oocytes retrieved with no statistical difference in complication or pregnancy rates. We also developed a scoring system that can serve as a useful screening tool for identifying women at increased risk of transabdominal oocyte retrieval.

Background Plasma Epstein–Barr virus (pEBV) DNA and fluorodeoxyglucose positron emission (PET) reflect tumour burden in advanced NPC. This study hypothesised that a dual endpoint based on assessing pEBV DNA clearance and PET response could predict early drug response. Methods Eligible patients underwent a computed tomography (CT) scan and dual PET-CT at baseline, a PET-CT at 4 weeks, and then a CT scan at 10 weeks after starting palliative or induction chemotherapy. Plasma EBV DNA clearance was determined. Results Fifty-eight out of 70 enrolled patients completed all imaging and 50/58 had falling pEBV DNA level, which allowed calculation of the clearance. At a median follow-up of 29.1 months, the dual endpoint (pEBV DNA clearance ≤ 10 days and > 50% drop in sum of SUVmax of target lesions) was an independent indicator of overall survival (hazard ratio (HR) = 0.135, 95% CI = 0.039 to 0.466, p = 0.0015) and progression-free survival (HR = 0.136, 95% CI = 0.048 to 0.385, p = 0002). This dual endpoint could predict subsequent response by Response Evaluation Criteria In Solid Tumours (RECIST) criteria at 10 weeks after chemotherapy. Conclusions Early PET-CT response and pEBV DNA clearance could predict survival and subsequent response. This dual endpoint is an innovative tool for assessing early drug response.

Custom reading guides for a large-enrollment introductory biology course were created to help students read their textbooks. Results showed that full completion of reading guides before class was significantly correlated with improved exam performance. Reading guides may be a simple way to promote student reading and improve learning., High-structure courses or flipped courses require students to obtain course content before class so that class time can be used for active-learning exercises. While textbooks are used ubiquitously in college biology courses for content dissemination, studies have shown that students frequently do not read their textbooks. To address this issue, we created preclass reading guides that provided students with a way to actively engage with the required reading for each day of class. To determine whether reading guide completion before class is associated with increased performance, we surveyed students about their use of reading guides in two sections of a large-enrollment (400+ students) introductory biology course and used multiple linear regression models to identify significant correlations. The results indicated that greater than 80% of students completed the reading guides before class and that full completion of the reading guides before class was significantly positively correlated with exam performance. Reading guides in most cases were used similarly between different student groups (based on gender, ethnicity, and aptitude). These results suggest that optional preclass reading guides may help students stay on track to acquire course content in introductory biology and thus result in improved exam performance.

The prognostic significance of KRAS, NRAS, PIK3CA and BRAF mutations was evaluated in Chinese patients with metastatic colorectal cancer (CRC).Tumor samples from 183 patients were retrospectively tested for KRAS, NRAS, PIK3CA and BRAF mutations. Multivariate analysis was performed to determine the relationship between mutational status, drug response and survival.Over 70% of patients received two or more lines of chemotherapy, 50% had cetuximab and 18% had bevacizumab. The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations was 45, 3.2, 5 and 20%, respectively. For the entire cohort, the median overall survival was 24 months (95% confidence interval [CI] = 20.4-26.4 months). Of the genes tested, only KRAS mutation was an independent prognostic factor with a multivariate hazard ratio of 1.5 (95% CI = 1.05-2.16, P = 0.03). In the subgroup of patients who received cetuximab-based therapy in the first-line setting, KRAS mutation was associated with a lack of response to chemotherapy (28% vs 66%, chi-square, P = 0.01). Patients with KRAS mutant tumors (or KRAS wild-type tumors that harbored BRAF and/or PIK3CA mutations) tended to have lower response rates to chemotherapy and/or cetuximab (P = not significant). The number of NRAS mutant cases was too small to allow any statistical analysis.The prevalence of KRAS, NRAS, BRAF and PIK3CA mutations in this cohort is consistent with reports from non-Asian populations, and KRAS mutation has both prognostic and predictive significance in Chinese patients with metastatic CRC.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Several important scientific discoveries in the molecular biology of CRC have changed clinical practice in oncology. These included the comprehensive genome-wide profiling of CRC by the Cancer Genome Atlas Network, the discovery of mutations along the RAS-RAF signaling pathway as major determinants of response to antibodies against the epidermal growth factor receptor, the elucidation of new molecular subsets of CRC or gene signatures that may predict clinical outcome after adjuvant chemotherapy, and the innovative targeting of the family of vascular endothelial growth factor and receptors. These new data have allowed oncologists to individualize drug therapy on the basis of a patient's tumor's unique molecular profile, especially in the management of metastatic CRC. This review article will discuss the progress of personalized medicine in the contemporary management of CRC.