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To determine the predictive value of the modified Frailty Index (mFI) in evaluating sarcopenia and clinical outcomes in patients undergoing 1-level or 2-level transforaminal lumbar interbody fusion (TLIF).Patients who underwent a 1-level or 2-level TLIF between 2012 and 2020 were retrospectively identified. Frailty was compared among groups using mFI, and sarcopenia was classified by the psoas muscle cross-sectional area. Bivariate statistics compared demographics, comorbidities, and clinical outcomes. A linear regression model was developed using the Charlson Comorbidity Index (CCI) or mFI as independent variables to determine potential predictors for improvement in 1-year patient-reported outcomes.Of 488 included patients, 60 were severely frail and 60 patients had sarcopenia, but sarcopenia was not associated with patient frailty (P = 0.469). Severely frail patients had worse baseline Oswestry Disability Index (ODI) (P0.001), Mental Component Score-12 (P = 0.001), and Physical Component Score-12 (P0.001), and worse improvement in ODI (P = 0.037), Physical Component Score-12 (P0.001), and visual analog scale (VAS) back (P = 0.007). mFI was an independent predictor of poorer improvement in VAS back and ODI, whereas age + CCI in addition predicted poorer improvement in VAS leg. Patients with higher mFI experienced longer length of stay, less frequent home discharge, and higher rates of complications, but similar readmission and reoperation rates.Frailer patients experience poorer improvement in back pain, physical functioning, and disability after TLIF. mFI and the combination of age and CCI comparably predict patient-reported outcomes but do not correlate to baseline sarcopenia. Frailty increased the risk of complications, length of hospital stay, and risk of nonhome discharge.

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.

Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are two distinct pathologies of retinal angiogenesis with overlapping clinical features.Examination, multimodal imaging, and genetic testing were used to guide diagnosis and treatment.We report a combined phenotype of X-linked FEVR and ROP in a 4-month-old girl with mosaic Turner syndrome with ring X chromosome born at 26 weeks gestational age. She was initially diagnosed with atypical ROP with a vitreous band causing a localized traction retinal detachment, inferotemporal to the macula in the right eye, vessels to posterior zone 2 with no clear ridge temporally in the left eye, and fluorescein leakage in both eyes. Due to the suspicion of concurrent FEVR, genetic testing using a vitreoretinopathy panel was performed which revealed a mosaic Turner syndrome associated with 45,X/46,X,r(X), subsequently confirmed by chromosome analysis. The deleted region in the ring X chromosome included the NDP and RS1 genes. The patient was treated with laser photocoagulation of the peripheral avascular retina and sub-Tenon's triamcinolone injection in both eyes, intravitreal injection of bevacizumab in the left eye, and pars plicata vitrectomy in the right eye.In premature neonates with atypical ROP, a clinical suspicion of concurrent FEVR or similar vasculopathy is important and genetic testing may elucidate a genetic etiology, which could influence management and prognosis. Turner syndrome can be connected with co-occurring Mendelian gene disorders, particularly in individuals with mosaicism. The concurrence of FEVR and ROP appears to result in atypical and possibly more severe phenotypes.

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: The COVID pandemic has impacted almost every aspect of human interaction, causing global changes in financial, health care, and social environments for the foreseeable future. More than 1.3 million of the 4 million cases of COVID-19 confirmed globally as of May 2020 have been identified in the United States, testing the capacity and resilience of our hospitals and health care workers. The impacts of the ongoing pandemic, caused by a novel strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have far-reaching implications for the future of our health care system and how we deliver routine care to patients. The adoption of social distancing during this pandemic has demonstrated efficacy in controlling the spread of this virus and has been the only proven means of infection control thus far. Social distancing has prompted hospital closures and the reduction of all non-COVID clinical visits, causing widespread financial despair to many outpatient centers. However, the need to treat patients for non-COVID problems remains important despite this pandemic, as care must continue to be delivered to patients despite their ability or desire to report to outpatient centers for their general care. Our national health care system has realized this need and has incentivized providers to adopt distance-based care in the form of telemedicine and video medicine visits. Many institutions have since incorporated these into their practices without financial penalty because of Medicare’s 1135 waiver, which currently reimburses telemedicine at the same rate as evaluation and management codes (E/M Codes). Although the financial burden has been alleviated by this policy, the practitioner remains accountable for providing proper assessment with this new modality of health care delivery. This is a challenge for most physicians, so our team of national experts has created a reference guide for musculoskeletal and neurologic examination selection to retrofit into the telemedicine experience. Objectives: To describe and illustrate musculoskeletal and neurologic examination techniques that can be used effectively in telemedicine. Study Design: Consensus-based multispecialty guidelines. Setting: Tertiary care center. Methods: Literature review of the neck, shoulder, elbow, wrist, hand, lumbar, hip, and knee physical examinations were performed. A multidisciplinary team comprised of physical medicine and rehabilitation, orthopedics, rheumatology, neurology, and anesthesia experts evaluated each examination and provided consensus opinion to select the examinations most appropriate for telemedicine evaluation. The team also provided consensus opinion on how to modify some examinations to incorporate into a nonhealth care office setting. Results: Sixty-nine examinations were selected by the consensus team. Household objects were identified that modified standard and validated examinations, which could facilitate the examinations.The consensus review team did not believe that the modified tests altered the validity of the standardized tests.Limitations: Examinations selected are not validated for telemedicine. Qualitative and quantitative analyses were not performed. Conclusions: The physical examination is an essential component for sound clinical judgment and patient care planning. The physical examinations described in this manuscript provide a comprehensive framework for the musculoskeletal and neurologic examination, which has been vetted by a committee of national experts for incorporation into the telemedicine evaluation. Key words: COVID, pain, telemedicine, physical examination, spine, shoulder, elbow, hand, hip, knee

The JAK family of non-receptor tyrosine kinases includes four subtypes (JAK1, JAK2, JAK3, and TYK2) and is responsible for signal transduction downstream of diverse cytokine receptors. JAK inhibitors have emerged as important therapies for immuno(onc)ological disorders, but their use is limited by undesirable side effects presumed to arise from poor subtype selectivity, a common challenge for inhibitors targeting the ATP-binding pocket of kinases. Here, we describe the chemical proteomic discovery of a druggable allosteric cysteine present in the non-catalytic pseudokinase domain of JAK1 (C817) and TYK2 (C838), but absent from JAK2 or JAK3. Electrophilic compounds selectively engaging this site block JAK1-dependent transphosphorylation and cytokine signaling, while appearing to act largely as “silent” ligands for TYK2. Importantly, the allosteric JAK1 inhibitors do not impair JAK2-dependent cytokine signaling and are inactive in cells expressing a C817A JAK1 mutant. Our findings thus reveal an allosteric approach for inhibiting JAK1 with unprecedented subtype selectivity.

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.

The cnidarian model organism Hydra has long been studied for its remarkable ability to regenerate its head, which is controlled by a head organizer located near the hypostome. The canonical Wnt pathway plays a central role in head organizer function during regeneration and during bud formation, which is the asexual mode of reproduction in Hydra. However, it is unclear how shared the developmental programs of head organizer genesis are in budding and regeneration. Time-series analysis of gene expression changes during head regeneration and budding revealed a set of 298 differentially expressed genes during the 48-h head regeneration and 72-h budding time courses. In order to understand the regulatory elements controlling Hydra head regeneration, we first identified 27,137 open-chromatin elements that are open in one or more sections of the organism body or regenerating tissue. We used histone modification ChIP-seq to identify 9,998 candidate proximal promoter and 3,018 candidate enhancer-like regions respectively. We show that a subset of these regulatory elements is dynamically remodeled during head regeneration and identify a set of transcription factor motifs that are enriched in the enhancer regions activated during head regeneration. Our results show that Hydra displays complex gene regulatory structures of developmentally dynamic enhancers, which suggests that the evolution of complex developmental enhancers predates the split of cnidarians and bilaterians.

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 present estimates of intergenerational mobility in self-reported health status (SRHS) in the US using data from the PSID. We estimate that the rank-rank slope in SRHS is 0.26. We show that including both parent health and income in models of intergenerational mobility increases the explanatory power of child outcomes. We construct a monetary metric for health and then use this to combine income and health into a measure of welfare and estimate the rank-rank slope to be about 0.4 for this new measure. Finally, we document striking health mobility gaps by race, region and parent education.

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.

Xenophobia against Asian American and Pacific Islander (AAPI) communities has spanned decades of American history, recently escalating in the context of the COVID-19 pandemic. According to the Asian Pacific Policy and Planning Council, there were 2583 reports of anti-Asian hate incidents as of August 2020, with reports only rising [1]. The federal government has done little to ameliorate this racial discrimination. Although H. Res 908, condemning all forms of anti-Asian sentiment, passed in September, 2020, the resolution took over 6 months to pass with 164 members of the House voting against the resolution. The national response to AAPI xenophobia parallels the experiences of the AAPI community within medicine, promoting a cycle of mental health issues stemming from prejudice and lack of systemic support. In particular, AAPI students in the medical field face the same encounters of discrimination in addition to the stress and pressure associated with medical school. Students witness encounters of xenophobia within their future career paths, instigating a sense of fear and uncertainty of how they will be perceived by future patients [2]. Concerns of xenophobia are compounded by the model minority myth, which implicates that academic achievement and accomplishments define self-worth, value, and identity [3]. A profound repercussion is that this leads to an unwillingness to seek out help and address mental health concerns within the AAPI community. Ultimately, there lies a challenge as to how we can adequately support our current AAPI medical community. Firstly, an increase in mental health support for AAPI students is pertinent, as this increase may incentivize students to seek help. Secondly, medical education requires more topics regarding diversity, which aid in dismantling the model minority myth while teaching faculty about the presence and history of xenophobia. Lastly, systemic lack of representation necessitates an institutional push for more Asian-American representation in academia. Despite Asians being over-represented in medical recruitment, AAMC reports that only 6% of Asians are professors, 3.52% are chairpersons, and 0% are deans [4]. The COVID-19 pandemic has illustrated how pervasive AAPI xenophobia is both within and beyond the medical institution; therefore, we have the responsibility to mitigate this dilemma.

COVID-19 is a droplet-transmitted potentially fatal coronavirus pandemic affecting the world in 2020. The WHO recommended social distancing and human-to-human contact was discouraged to control the transmission. It has put many countries in a state of lockdown and sporting events (including the 2020 Olympics) have been affected. Participation in sports and exercise, typically regarded as healthy activities, were also debated. The local professional football leagues, governed by the Hong Kong Football Association, ultimately postponed all matches after much deliberation on the transmission risk for the spectators and on-field players. Large spectating crowds are well-known to be infectious hazards, but the infection risk for on-field players is less recognized. To address this question, we performed a small-scale investigation that showed, in a 90 min match, the average duration of close contact between players was 19 min and each player performed an average of 52 episodes of infection-risky behaviours. This suggests that the infection risk was high for the players, even without spectators. Aside from watching professionals exercise, many people opted to hike in the countryside during the weekends to avoid city crowds. This led to a widespread discussion on the issue of masked versus unmasked hiking. We performed a laboratory study to investigate the physiological effect of wearing a facemask during simulated hiking and found that it significantly elevated heart rate and perceived exertion. The clinical implication is that hikers need to realize masks increase the physiological burden, especially in those with multiple underlying comorbidities. Elite athletes, especially those training for the upcoming Olympics, needed to balance and reschedule their training regime since the risk of deconditioning versus the risk of infection was a genuine dilemma for themselves and their team. We described the multiple infection-control measures imposed by the national team training centre to help strike this balance. Amidst a global pandemic affecting millions; staying active is good, but staying safe is paramount., Highlights • Staying active during a pandemic like COVID-19 requires smart tactics. • As the team physicians, we described the strategies utilised to balance infection control and sports during COVID-19 in the professional football league and the Olympic team's training. • Contact sports like football, even without spectating crowds, pose an infection risk to the players; while exercising with face-masks cases a significant increase in physiological demand.

Filtration of protein A eluates inline with a chromatography column is a common challenge for monoclonal antibody (mAb) purification due to the high system backpressure during elution, which can result in system shut down or require a decreased elution flow rate. The inability to filter inline not only poses a risk for process deviations, but can also lead to tank constraints and microbial ingress risk. Here, we evaluated and described a novel approach for identifying filters for inline filtration of protein A eluates at pilot scale. We fractionated the protein A eluates into 0.25 column volume fractions to screen filters under constant pressure or constant flow conditions. We observed that filtration properties for eluate fractions are significantly different from the offline eluate, and the conventional filter sizing study using elution pool is not able to predict inline filtration behavior. Through the submicron particle counts and size distribution in pre- and post-filtration samples, we determined that both attributes contribute to the high pressure across the filters. A successful proof-of-concept experiment on a column 10 cm in diameter inline with the filter train selected validated this fractionation method, and the approach was applied to a different mAb molecule to confirm effectiveness.

The reformation of naphtha to obtain valuable chemical intermediates such as BTX has attracted much attention. Here we report a novel catalytic process whereby a bimetallic heterogeneous catalyst in the form of Zn-Pt/HZSM-5 is applied to a flow reactor system to reform a complex naphtha feed under a methane environment. Different levels of acidity of the HZSM-5 support are tested with a superior performance witnessed using a SiO2:Al2O3 ratio at 80. Further testing is conducted using Zn as a dehydrogenating component with improved performance witnessed when Zn is loaded to a certain degree. A metal promoter is then combined with Zn to compare the effect of different promoters with superior performance witnessed using Ga and Pt as promoters with Zn. BTX selectivity and BTX yield are reported as 86.44% and 34.22% respectively under the Zn-Pt/HZSM-5 catalyst. External site coverage improves performance for all bimetallic catalysts with the exception of Zn-Pt/HZSM-5, suggesting that Pt might not promote the migration of metal functions to the internal pores during synthesis. XRD spectra demonstrate that Pt addition results in a more intact crystal structure after reaction when compared to Zn alone·NH3-TPD and DRIFT analyses show a reduced amount of strong acidic sites upon metal loading with an increase in the number of Lewis acid sites and reduced Bronsted sites. This change in acidity could be one of the reasons for an improved performance when Zn-Pt/HZSM-5 is employed. The effect of methane is also witnessed over Zn-Pt/HZSM-5 with improved selectivity, yield (BTX and liquid) and active metal dispersion when compared to a nitrogen environment, suggesting the possible incorporation of methane into the products, BTX in particular. Ultimately, the catalyst employed here opens an avenue for further research into the possible industrial application of naphtha aromatization to form valuable chemical products under methane environment.

We sought to characterize parents who look for second medical opinions to get human papillomavirus (HPV) vaccine for their children and whether second opinions influenced acceptance of HPV vaccine. Between July and August 2019, we conducted an online survey with a national sample of 906 parents of adolescents ages 11–17. We used multivariable logistic regression to assess correlates of looking for second opinions on HPV vaccination. For those who looked for second opinions, the survey assessed their HPV vaccine information needs and whether their child ultimately received the vaccine. Overall, 15% of parents reported looking for second opinions. Parents were more likely to look for second opinions if their self-reported knowledge about HPV vaccine was the same (Odds ratio [OR] = 1.94; 95% confidence interval [CI]:1.13, 3.30) or more (OR = 3.97; 95% CI:2.35, 6.73) than their child’s provider, or if they reported seeing HPV vaccine information on social media (OR = 2.50; 95% CI:1.69, 3.69). Parents were also more likely to look for second opinions if they were male, reported low vaccine confidence, disagreed with social norms favoring HPV vaccination, or had a young child (all p

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.

The cnidarian model organism Hydra has long been studied for its remarkable ability to regenerate its head, which is controlled by a head organizer located near the hypostome. Cnidarians and bilaterians diverged about 600 millions years ago but the gene contents of species of both phyla are surprisingly similar despite divergent morphologies and functions. While little is known about the role ofcis-regulatory elements in cnidarians, understanding gene regulatory mechanisms in cnidarians can potentially shed light on metazoan evolution. The canonical Wnt pathway plays a central role in head organizer function during regeneration and during bud formation, which is the asexual mode of reproduction in Hydra. However, it is unclear how shared the developmental programs of head organizer genesis are in budding and regeneration. Time-series analysis of gene expression changes during head regeneration and budding revealed a set of 298 differentially expressed genes during the 48-hour head regeneration and 72-hour budding time-courses. In order to understand the regulatory elements controlling hydra head regeneration, we first identified 27,137 open-chromatin elements that are open in one or more sections of organism. We used histone modification ChIP-seq to identify 9998 candidate proximal promoter and 3018 candidate enhancer-like regions respectively. We show that a subset of these regulatory elements is dynamically remodeled during head regeneration and identify a set of transcription factor motifs that are enriched in the enhancer regions activated during head regeneration. Our results show that Hydra displays complex gene regulatory structures of developmentally dynamic enhancers, which suggests that the evolution of complex developmental enhancers predates the split of cnidarians and bilaterians.

Low-income Americans who became eligible to enroll in Medicaid due to the Affordable Care Act saw their medical debt cut in half.

We examine the effect of the Medicaid expansions under the 2010 Patient Protection and Affordable Care Act (ACA) on consumer financial outcomes using data from a major credit reporting agency for a large, national sample of adults. We employ the synthetic control method to compare individuals living in states that expanded Medicaid to those that did not. We find that the Medicaid expansions significantly reduced the number of unpaid bills and the amount of debt sent to third-party collection agencies among those residing in zip codes with the highest share of low-income, uninsured individuals. Our estimates imply a reduction in collection balances of approximately $1,140 among those who gain Medicaid coverage due to the ACA. Our findings suggest that the ACA Medicaid expansions had important financial impacts beyond increasing health care use.

This article examines how the financial health changes following an individual's enrollment in Michigan's Medicaid program (Healthy Michigan Program, HMP). We use unique data that link credit reports of HMP enrollees to Medicaid administrative data on enrollment and use of healthcare services. We find that Medicaid enrollment is associated with large improvements in several measures of financial health, including reductions in unpaid bills, medical bills, over limit credit card spending, and public records (such as evictions, judgments, and bankruptcies). These improvements are apparent across several subgroups, although individuals with greater medical need, such as those with chronic illnesses, experience the largest benefits.

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.

Aim The prognostic significance of KRAS, NRAS, PIK3CA and BRAF mutations was evaluated in Chinese patients with metastatic colorectal cancer (CRC). Method 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. Result 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. Conclusion 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.

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.

We examine the effect of the Medicaid expansions under the 2010 Patient Protection and Affordable Care Act (ACA) on consumer financial outcomes using data from a major credit reporting agency for a large, national sample of adults. We employ the synthetic control method to compare individuals living in states that expanded Medicaid to those that did not. We find that the Medicaid expansions significantly reduced the number of unpaid bills and the amount of debt sent to third-party collection agencies among those residing in zip codes with the highest share of low-income, uninsured individuals. Our estimates imply a reduction in collection balances of approximately $1,140 among those who gain Medicaid coverage due to the ACA. Our findings suggest that the ACA Medicaid expansions had important financial impacts beyond health care use.