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Background: Rhinoplasty patients often present with specific concerns and are frequently exacting in their demands and expectations of the surgical experience.Objectives: The authors assess the presenting complaints expressed during the rhinoplasty consultation process and compare the presentations of primary versus revision rhinoplasty patients.Methods: A retrospective review of 400 consecutive rhinoplasty patients was performed. Demographic information and patient concerns regarding nasal appearance and function were recorded. Complaint frequencies (as well as rank order) were compared between primary and revision patients. Statistically significant associations were compared in more detail through logistic regression models.Results: Primary rhinoplasty patients were significantly more likely to cite "too large" and "dorsal hump" as motivating concerns. Conversely, revision rhinoplasty patients were far more likely to cite concern regarding a "crooked nose," "tip asymmetry," "wide or large nostrils," "dorsal sloop," and "columellar show." Revision rhinoplasty patients also complained of issues such as "alar retraction," "pointy tip," and "nasal scarring," which were almost negligible in frequency in the primary rhinoplasty group.Conclusions: Patients presenting for primary rhinoplasty commonly seek a smaller, more refined nasal appearance. Patients with prior rhinoplasty operations are far more likely to raise concern regarding crookedness or asymmetries. By comparing the presentations of primary and revision rhinoplasty patients-and delineating the common indications for revision operations-novice rhinoplasty surgeons may be able to avoid certain pitfalls at the outset, thereby reducing their revision rates. The data may also assist surgeons in developing a more targeted approach to the consultation process in the revision setting. [ABSTRACT FROM AUTHOR]

Objectives: To assess student exposure to types of pharmacy practice, evaluate awareness and perceptions of community pharmacy residencies, and identify areas of postgraduate training of interest to student pharmacists.Design: Cross-sectional, descriptive, online survey study.Setting: United States, January to April 2008.Participants: Student pharmacists in the final 2 years of the doctor of pharmacy (PharmD) program.Intervention: An online survey was administered to students in the final 2 years of the PharmD program at randomly selected schools of pharmacy by region throughout the United States.Main Outcome Measures: Awareness of student pharmacists regarding community pharmacy residencies and interest in postgraduate training.Results: 254 surveys were completed during the study period. Of the respondents, 95% had previous experience working in a community pharmacy setting. Nearly 90% were aware of community pharmacy residencies. Students who indicated opportunities to publish (odds ratio 2.4 [95% CI 1.34-4.1]), teaching students (2.1 [1.36-3.14]), enjoying the job atmosphere (4.9 [1.54-15.60]), and clinically challenging (4.3 [2.15-8.67]) as desirable career attributes were more likely to be interested in postgraduate training. No significant differences existed in the information sources sought by students interested in community pharmacy residency programs (CPRPs) compared with those interested in other types of postgraduate training.Conclusion: The significant predicators of student pharmacists interested in pursuing postgraduate training are in alignment with CPRP training. Further research is needed to market the value of CPRPs through the identified information sources. [ABSTRACT FROM AUTHOR]

Introduction: The Utah Pediatric Trauma Network (UPTN), established in 2019, is a collaboration of hospitals that have implemented guidelines to optimize pediatric trauma care. The purpose of this study was to determine whether preventable transfer (PT) rates decreased following the establishment of the UTPN and what hospital characteristics were associated with decreased preventable transfers., Methods: Children with traumatic injuries transferred from hospitals in the UPTN to the state's only Level I Pediatric Trauma Center between 2013 and 2023 were retrospectively analyzed. A PT was a child discharged within 48 h of arrival without surgical intervention or advanced imaging studies. The main hospital-level outcome measure was an overall decrease in PT after the UPTN establishment in 2019., Results: After 2019, 34 of the 46 hospitals meeting inclusion criteria saw a decrease in the percentage of PTs, while 12 saw an increase in PT rate, with an overall median change of -7 % (IQR -14 %, 0 %). We observed that hospitals with decreased PT had higher rates of PT before the establishment of the UPTN and had higher overall transfer volume than hospitals without a decreased PT rate. Can we put the overall p value in this?, Conclusion: Most hospitals were able to successfully decrease PT rates following the creation of the UPTN. More smaller hospitals did not successfully decrease PT, so more work may need to be done to target lower-volume hospitals., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Growing rates of childhood obesity globally create concern for individuals' health outcomes and demands on health systems. While many policy approaches focus on macro-level interventions, we examine how the type of stability of a family structure might provide opportunities for policy interventions at the micro level. We examine the association between family structure trajectories and childhood overweight and obesity across three Anglophone countries using an expanded set of eight family structure categories that capture biological relationships and instability, along with potential explanatory variables that might vary across family trajectories and provide opportunities for intervention, including access to resources, family stressors, family structure selectivity factors, and obesogenic correlates. We use three datasets that are representative of children born around the year 2000 and aged 11 years old in Australia ( n = 3329), the United Kingdom ( n = 11,542), and the United States ( n = 8837) and nested multivariate multinomial logistic regression models. Our analyses find stronger relationships between child overweight and obesity and family structure trajectories than between child obesity and obesogenic factors. Children in all three countries are sensitive to living with cohabiting parents, although in Australia, this is limited to children whose parents have been cohabiting since before their birth. In the UK and US, parents starting their cohabitation after the child's birth are more likely to have children who experience obesity. Despite a few differences across cross-cultural contexts, most of the relationship between family structures and child overweight or obesity is connected to differences in families' access to resources and by the types of parents who enter into these family structures. These findings suggest policy interventions at the family level that focus on potential parents' education and career prospects and on income support rather than interventions like marriage incentives.

A trending topic in pharmacy education is the importance of educating and exposing student pharmacists to topics of diversity, equity, inclusion, and antiracism (DEIA). Incorporation of diverse patient populations is one emerging learning opportunity for students in the DEIA space. This commentary presents the findings of seven pharmacy programs reporting similarities and differences in standardized patient (SP) recruitment and training, and their use in DEIA simulation learning activities. Common barriers of DEIA-centric SP activities in pharmacy programs were also identified and included recruitment of diverse SPs, lack of faculty knowledge for implementation of DEIA-focused simulations, and emotional protection of SPs involved. While no best practices or standardized processes exist, the authors provide suggestions for addressing barriers, and make a call to action for further research to determine best practices related to recruitment, training, and utilization of diverse SPs in simulation activities in pharmacy education., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to determine the validity and inter-rater reliability of radiographic assessment of sagittal deformity of femoral neck fractures., Design: This is a retrospective cohort study., Setting: Level 1 trauma center., Patients/participants: Thirty-one patients 65 years or older who sustained low-energy, Garden type I/II femoral neck fractures imaged with biplanar radiographs and either computed tomography or magnetic resonance imaging were included., Main Outcome Measurements: Preoperative sagittal tilt was measured on lateral radiographs and compared with the tilt identified on advanced imaging. Fractures were defined as "high-risk" if posterior tilt was ≥20 degrees or anterior tilt was >10 degrees., Results: Of 31 Garden type I/II femoral neck fractures, advanced imaging identified 10 high-risk fractures including 8 (25.8%) with posterior tilt ≥20 degrees and 2 (6.5%) with anterior tilt >10 degrees. Overall, there was no significant difference between sagittal tilt measured using lateral radiographs and advanced imaging ( P = 0.84), and the 3 raters had good agreement between their measurements of sagittal tilt on lateral radiographs (interclass correlation coefficient 0.79, 95% confidence interval [0.65, 0.88], P < 0.01). However, for high-risk fractures, radiographic measurements from lateral radiographs alone resulted in greater variability and underestimation of tilt by 5.2 degrees (95% confidence interval [-18.68, 8.28]) when compared with computed tomography/magnetic resonance imaging. Owing to this underestimation of sagittal tilt, the raters misclassified high-risk fractures as "low-risk" in most cases (averaging 6.3 of 10, 63%, range 6 - 7) when using lateral radiographs while low-risk fractures were rarely misclassified as high-risk (averaging 1.7 of 21, 7.9%, range 1 - 3, P = 0.01)., Conclusions: Lateral radiographs frequently lead surgeons to misclassify high-risk sagittal tilt of low-energy femoral neck fractures as low-risk. Further research is necessary to improve the assessment of sagittal plane deformity for these injuries., Level of Evidence: Level IV diagnostic study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Collagen is the most prevalent of Nature's structural proteins, and is found in the extracellular matrices of animals. The structures of collagen molecules and aggregates are chiral, which leads to the rotation of transmitted, plane-polarized light. Here, it is shown that the concentrations of chiral molecules and aggregates in the optically transparent, adipose eyelid of Atlantic mackerel ( Scomber scombrus ) can be so high, that plane-polarized light in the visible spectrum is rotated by tens to hundreds of degrees, depending on wavelength (the optical rotatory dispersion (ORD)). This gives rise to intensely coloured images of eyelid samples when illuminated with white light and viewed between crossed polarizers. The ORD in the visible spectrum is measured with monochromatic light sources, and using this dispersion, the variation of optical thickness within a sample (proportional to collagen concentration and path length) is determined. The agreement between observed and simulated white-light images is almost perfect. While collagen provides vital mechanical rigidity to animal tissue, it might also possess optical properties that are useful for vision and camouflage.

Background: Patients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear., Objective: To determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization., Design: Prospective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087)., Setting: Done during 2021 to 2022 among 127 U.S. hospitals., Participants: Adults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation., Intervention: 2.5 mg of apixaban versus placebo twice daily for 30 days., Measurements: The primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding., Results: Enrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment., Limitations: The introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity., Conclusion: The incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive., Primary Funding Source: National Institutes of Health.

Background and Purpose: Medical improvisation (improv) is increasingly being used to teach physicians, nurses, and other caregivers how to better communicate with patients and other members of the healthcare team. This article describes how improvisational activities were incorporated within an existing pharmacy practice lab course and how to implement improv games targeting specific communication skills., Educational Activity and Setting: Three hours of improvisational activities were incorporated into a semester-long pharmacy practice lab course. Partner games such as "the mirror" and group games such as "out-of-order story" were played and connected to communication skills related to counseling or taking a patient's history. Additional activities were introduced targeting specific areas of weakness identified in a formative assessment., Findings: A survey was used to assess student perceptions of the improv activities. Students were largely able to connect the skills learned in improv to pharmacy, and some provided examples of how they were already implementing these skills in practice., Summary: This article provides a user manual so that faculty with little to no improv experience can include these activities in their communications courses., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

The coronavirus pandemic has caused a devastating impact across the planet. Millions of lives lost and economic structures are struggling to remain afloat. Clinical effects of SARS CoV-2 virus include tiredness, fatigue, headache, cough, loss of appetite, fever, loss of sensations of taste, and smell as well as other respiratory difficulties. Pulmonary complications of coronavirus infections result in severe pneumonia with the final sequelae being sepsis, and end-stage respiratory failure. Further cardiovascular, neurological, hematological, and gastrointestinal complications build up to cause the demise of the immune system ultimately leading to death of the affected individual. The attack of the virus and the resultant reaction of the epithelial cells lining the respiratory tract have been in the limelight of most studies pertaining to the pandemic. However, a lesser number of studies have detailed the muscular and osseous pathologies that appear post-coronavirus infection. Inflammation post-infection, across the organ systems, may appear as a link to bone and joint pathology. Myalgia is a typical COVID-19 infection symptom. On the contrary, other musculoskeletal signs have very seldom been reported. Multimodality imaging techniques stand a chance at showing the diagnosis and the degree of follow-up after evaluation. Apart from myalgia, there are cases of arthralgia, myopathies, and neuropathies. According to numerous reports, there is the possibility of a link between the current drug regimen used to treat the SARS-CoV-2 infection and the musculoskeletal manifestations observed. In this study, we aim to shed light on the coronavirus pandemic and its association to various musculoskeletal manifestations, provide a different perspective of the infected patients, and address the major points that a clinician must take care while administering care to the patient. We will also address the present treatment in line with the various musculoskeletal symptoms observed., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Alexander et al.)

Studies describing gaps in care for youth with congenital heart disease (CHD), focus on those who have returned to care, but rarely those actively missing from care. Our objective was to determine barriers for young adults with CHD actively missing from cardiac care and to re-engage them in care. Retrospective single-center cohort study of cardiology clinic patients ages 15-21 years with CHD between 2012 and 2019 for patients actively missing from care (≥ 12 months beyond requested clinic follow-up). We conducted prospective interviews, offered clinic scheduling information, and recorded cardiac follow-up. Data analyzed using descriptive statistics, univariable, and multivariable logistic regression. Of 1053 CHD patients, 33% (n = 349) were actively missing. Of those missing, 58% were male and median age was 17 years (IQR 16-19). Forty-six percent were Non-Hispanic White, 33% Hispanic, and 9% Black. Moderately complex CHD was in 71%, and 62% had private insurance. Patients with simple CHD, older age at last encounter (18-21), and scheduled follow-up > 12 months from last encounter were more likely to be actively missing. Interviews were completed by 125 patients/parents (36%). Lack of cardiac care was reported in 52%, and common barriers included: insurance (33%), appointment scheduling (26%), and unknown ACHD center care (15%). Roughly half (55%) accepted appointment information, yet only 3% successfully returned. Many patients require assistance beyond CHD knowledge to maintain and re-engage in care. Future interventions should include scheduling assistance, focused insurance maintenance, understanding where to obtain ACHD care, and educating on need for lifelong care., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this paper, we report the effect of optical trapping on the enhancement factor for Raman spectroscopy, using a dielectric metasurface. It was found that a higher enhancement factor (up to 275%) can be obtained in a substrate immersed in water, where particles are freee to move, compared to a dried substrate, where the particles (radius [Formula: see text] nm, refractive index [Formula: see text]) are fixed on the surface. The highest enhancement is obtained at low concentrations because, this case, the particles are trapped preferentially in the regions of highest electric field (hotspots). For high concentrations, it was observed that the hotspots become saturated with particles and that additional particles are forced to occupy regions of lower field. The dielectric metasurface offers low optical absorption compared to conventional gold substrates. This aspect can be important for temperature-sensitive applications. The method shows potential for applications in crystal nucleation, where high solute supersaturation can be achieved near the high-field regions of the metasurface. The high sensitivity for SERS (surface-enhanced Raman spectroscopy) at low analyte concentrations makes the proposed method highly promising for detection of small biological particles, such as proteins or viruses.

This article considers the opportunities and challenges of transdisciplinary research on student learning in university settings. Fifty years ago, at a meeting in France that convened experts in education and psychology as well as higher education leaders, the term transdisciplinarity was coined as issues pertaining to the structure of the university and its impact on teaching and learning were considered. We argue that to move beyond what has already been discussed requires added insights from both the learning sciences and developmental sciences. In this article, these two areas are combined with the perspectives of higher education leaders. First, research is considered from the learning sciences on deep learning in relation to university learning and teaching. This body of work illustrates ways students need to be actively engaged in their learning and simultaneously frames teachers as facilitators of students' constructive efforts rather than disseminators of static knowledge. Second, perspectives from the developmental sciences on processes of development are reviewed, focusing on adolescence and emerging adulthood. Here we highlight the importance of considering developmental systems approaches to aspects of organizing learning at universities in light of extensive research on adolescents and emerging adults. Third, we examine new higher education frameworks that have focused on the importance of student engagement, integration and application of knowledge and the implications of these shifts for organizing higher education learning in more holistic ways, often at the national and transnational levels. In reviewing these three areas, we consider what assumptions are made about the learner, the role of teachers and others in enhancing student learning, and the interaction between learners and contexts where learning takes place. We argue that while progress is being made in undergraduate reform efforts, implementation has been uneven. To deliver on this important work will require further alignment of the sort Jantsch (1972) and Piaget (1972) claimed was central to transdisciplinary approaches, namely aligning these different areas through a systems approach that considers education as a purposeful human activity. This will involve alignment and support from the learning and developmental sciences, as well as local, national and transnational efforts and learning communities to support campus efforts., (Copyright © 2020 Budwig and Alexander.)

Mammalian hair cells develop their mechanosensory bundles through consecutive phases of stereocilia elongation, thickening, and retraction of supernumerary stereocilia. Many molecules involved in stereocilia elongation have been identified, including myosin-XVa. Significantly less is known about molecular mechanisms of stereocilia thickening and retraction. Here, we used scanning electron microscopy (SEM) to quantify postnatal changes in number and diameters of the auditory hair cell stereocilia in shaker-2 mice (Myo15 sh2 ) that lack both "long" and "short" isoforms of myosin-XVa, and in mice lacking only the "long" myosin-XVa isoform (Myo15 ∆N ). Previously, we observed large mechanotransduction current in young postnatal inner (IHC) and outer (OHC) hair cells of both these strains. Stereocilia counts showed nearly identical developmental retraction of supernumerary stereocilia in control heterozygous, Myo15 sh2/sh2 , and Myo15 ∆N/∆N mice, suggesting that this retraction is largely unaffected by myosin-XVa deficiency. However, myosin-XVa deficiency does affect stereocilia diameters. In control, the first (tallest) and second row stereocilia grow in diameter simultaneously. However, the third row stereocilia in IHCs grow only until postnatal day 1-2 and then become thinner. In OHCs, they also grow slower than taller stereocilia, forming a stereocilia diameter gradation within a hair bundle. The sh2 mutation disrupts this gradation and makes all stereocilia nearly identical in thickness in both IHCs and OHCs, with only subtle residual diameter differences. All Myo15 sh2/sh2 stereocilia grow postnatally including the third row, which is not a part of normal development. Serial sections with focused ion beam (FIB)-SEM confirmed that diameter changes of Myo15 sh2/sh2 IHC and OHC stereocilia resulted from corresponding changes of their actin cores. In contrast to Myo15 sh2/sh2 , Myo15 ∆N/∆N hair cells develop prominent stereocilia diameter gradation. Thus, besides building the staircase, the short isoform of myosin-XVa is essential for controlling the diameter of the third row stereocilia and formation of the stereocilia diameter gradation in a hair bundle.

Increasing evidence suggests a role for inflammation in neuropsychiatric conditions including autism spectrum disorder (ASD), a neurodevelopmental syndrome with higher prevalence in males than females. Here we examined the effects of early-life immune system activation (EIA)-comprising regimens of prenatal, early postnatal, or combined ("two-hit") immune activation-on the core behavioral features of ASD (decreased social interaction, increased repetitive behavior, and aberrant communication) in C57BL/6J mice. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C) on gestational day 12.5 to produce maternal immune activation (MIA). Some offspring also received lipopolysaccharide (LPS) on postnatal day 9 to produce postnatal immune activation (PIA). EIA produced disruptions in social behavior and increases in repetitive behaviors that were larger in males than in females. Ultrasonic vocalizations (USVs) were altered in both sexes. Molecular studies revealed that EIA also produced prominent sex-specific changes in inflammation-related gene expression in the brain. Whereas both sexes showed increases in pro-inflammatory factors, as reflected by levels of mRNA and protein, expression of anti-inflammatory factors was decreased in males but increased in females. Our findings demonstrate that EIA can produce sex-specific behavioral effects and immune responses in the brain, and identify molecular processes that may contribute to resilience in females.

Freestanding emergency departments (EDs), health care facilities that offer emergency care without being physically attached to a hospital, are becoming more common throughout the United States. Many individuals propose that these facilities can help alleviate the stress our current emergency care system faces and provide care to people with limited access to traditional hospital-based EDs. We reviewed the current literature on freestanding EDs to investigate whether these facilities are meeting those goals. We found that although they provide care that is generally similar in quality and cost to that of hospital-based EDs, freestanding EDs tend to cater to a more affluent patient population that already has access to health care instead of expanding care to underserved areas. This, coupled with a fragmented system of state-by-state regulation, leads us to recommend implementing more uniform licensing criteria from state to state, encouraging freestanding EDs to operate in more rural and underserved areas, and increasing price transparency., (Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Nutrition plays a key role in optimizing healing following surgery. The increased catabolic state postoperatively, coupled with a propensity for patients to be suffering from marginal nutritional deficiencies at baseline preoperatively, necessitates that the surgeon be attuned to the need for optimal perioperative nutritional support. This ensures the smoothest recovery and best possible outcomes in facial plastic surgery. Key nutrients include vitamin A, vitamin C, zinc, bromelain, arnica montana, arginine, glutamine, hydrolyzed collagen, vitamin B complex, and protein. The ability for patients to obtain this optimal supplementation in a single product is the ideal solution for both surgeon and patient., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Oral submucous fibrosis (OSMF) commonly seen in the South Asian countries is mostly associated with the chewing of areca nut (AN). Copper content in the AN has been implicated to play a major role in the pathogenesis of OSMF. It was found that most of the AN plantations in South India commonly use a copper-based fungicide, Bordeaux mixture (BM)., Objective: To evaluate the level of copper in the AN, root, and soil of the AN plantation with and without the application of BM and to correlate the role of copper in the pathogenesis of OSMF., Materials and Methods: ANs, roots, and soil were obtained from plantations located in Tanniadi, Kerala. Four areas were selected from the plantation with and without BM application. The samples were collected twice with the interval of 6 months during January 2015 and July 2015, respectively., Statistical Analysis: Arithmetic mean and standard deviation were calculated. The differences between means were calculated by paired sample t-test., Results: There was statistically significant difference in the copper content of ANs, soil, and roots from both groups (P < 0.05). Samples treated with BM showed significantly higher copper levels as compared to their counterparts in January and July 2015., Conclusions: External copper from BM and increased processing for the commercial products could collectively increase the total copper content of the commercial AN products, and this high copper concentration may be implicated to the pathogenesis and the increasing prevalence of OSMF., Competing Interests: None

Non-photochemical laser-induced nucleation (NPLIN) is the formation of a new phase from a metastable phase by the action of light on matter. Using millijoule, nanosecond laser pulses at visible and near-infrared wavelengths, it is possible to form the new phase localized in the volume of the beam. In the case of nucleating molecular solids, the laser polarization may have an effect on the particular polymorph that is formed. Despite the huge potential for applications of NPLIN, there is uncertainty regarding the molecular-scale mechanism, and various possible scenarios may well be relevant to nucleation in general and not just NPLIN. In this Perspective, the discovery and phenomenology of NPLIN are described, putative mechanisms are outlined, and some observations on the broader class of nucleation phenomena are given.

Inflammatory processes may be involved in the pathophysiology of neuropsychiatric illnesses including autism spectrum disorder (ASD). Evidence from studies in rodents indicates that immune activation during early development can produce core features of ASD (social interaction deficits, dysregulation of communication, increases in stereotyped behaviors, and anxiety), although the neural mechanisms of these effects are not thoroughly understood. We treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C), which simulates a viral infection, or vehicle on gestational day 12.5 to produce maternal immune activation (MIA). Male offspring received either vehicle or lipopolysaccharide, which simulates a bacterial infection, on postnatal day 9 to produce postnatal immune activation (PIA). We then used optogenetics to address the possibility that early developmental immune activation causes persistent alterations in the flow of signals within the mPFC to basolateral amygdala (BLA) pathway, a circuit implicated in ASD. We found that our MIA regimen produced increases in synaptic strength in glutamatergic projections from the mPFC to the BLA. In contrast, our PIA regimen produced decreases in feedforward GABAergic inhibitory postsynaptic responses resulting from activation of local circuit interneurons in the BLA by mPFC-originating fibers. Both effects were seen together when the regimens were combined. Changes in the balance between excitation and inhibition were differentially translated into the modified spike output of BLA neurons. Our findings raise the possibility that prenatal and postnatal immune activation may affect different cellular targets within brain circuits that regulate some of the core behavioral signs of conditions such as ASD. SIGNIFICANCE STATEMENT Immune system activation during prenatal and early postnatal development may contribute to the development of autism spectrum disorder (ASD). Combining optogenetic approaches and behavioral assays that reflect core features of ASD (anxiety, decreased social interactions), we uncovered mechanisms by which the ASD-associated behavioral impairments induced by immune activation could be mediated at the level of interactions within brain circuits implicated in control of emotion and motivation (mPFC and BLA, specifically). Here, we present evidence that prenatal and postnatal immune activation can have different cellular targets in the brain, providing support to the notion that the etiology of ASD may be linked to the excitation/inhibition imbalance in the brain affecting the signal flow within relevant behavior-driving neural microcircuits., (Copyright © 2018 the authors 0270-6474/18/383358-15$15.00/0.)

Increasing evidence suggests a role for inflammation in neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous work in rodents has established that immune activation during critical developmental periods can cause phenotypes that reproduce core features of ASD, including decreased social interaction, aberrant communication, and increased repetitive behavior. In humans, ASD is frequently associated with comorbid medical conditions including sleep disorders, motor hyperactivity, and seizures. Here we use a 'two-hit' immune-activation paradigm to determine whether perinatal immune activation can also produce these comorbid features in mice. In this paradigm, we treated timed-pregnant mice with polyinosinic:polycytidylic acid (Poly I:C), which simulates a viral infection, on gestational day 12.5 according to an established maternal immune activation regimen. A subset of the offspring also received a second 'hit' of lipopolysaccharide (LPS), which simulates a bacterial infection, on postnatal day 9. At 6 weeks of age, mice were implanted with wireless telemetry transmitters that enabled continuous measurements of electroencephalography (EEG), electromyography (EMG), locomotor activity, and subcutaneous temperature. Effects at 7 and 12 weeks of age were compared. Both prenatal Poly I:C and postnatal LPS produced changes in locomotor activity and temperature patterns, increases in slow-wave sleep, and shifts in EEG spectral power, several of which persisted at 12 weeks of age. Postnatal LPS also produced persistent increases in spontaneous bursts of epileptiform activity (spike-wave discharges) that occurred predominantly during sleep. Our findings demonstrate that early-life immune activation can lead to long-lasting physiologic perturbations that resemble medical comorbidities often seen in ASD and other neuropsychiatric conditions.

The effects of a rapidly heated nanoparticle on the structure of a concentrated aqueous salt solution are studied using molecular dynamics simulations. A diamond-like nanoparticle of radius 20 Å is immersed in a sodium-chloride solution at 20% above the experimental saturation concentration and equilibrated at T = 293 K and P = 1 atm. The nanoparticle is then rapidly heated to several thousand degrees Kelvin, and the system is held under isobaric-isoenthalpic conditions. It is observed that after 2-3 ns, the salt ions are depleted far more than water molecules from a proximal zone 15-25 Å from the nanoparticle surface. This leads to a transient reduction in molality in the proximal zone and an increase in ion clustering in the distal zone. At longer times, ions begin to diffuse back into the proximal zone. It is speculated that the formation of proximal and distal zones, and the increase in ion clustering, plays a role in the mechanism of nonphotochemical laser-induced nucleation.

Recent advances in the treatment of neuroendocrine tumors (NET), including the combination regimen of capecitabine and temozolomide (CAPTEM), have mostly focused on grade 1 and 2 pancreatic neuroendocrine tumors (pNET). We undertook a retrospective review of 38 patients with advanced NET treated with CAPTEM, including patients with non-pancreatic tumors as well as grade 2 and 3 tumors. O 6 -methylguanine DNA methyltransferase (MGMT) expression was assessed as a predictive biomarker. We found that CAPTEM demonstrated activity in patients with all grades and in pNET and non-pNET. Median progression free survival (mPFS) was 13.0 months (95% CI: 5.6-17.0) and median overall survival (mOS) 29.3 months (95% CI 17.7 - 45.3). Among evaluable patients, there were 11 (38%) partial responses, 15 (52%) stable disease, and 3 (10%) progressive disease for a disease control rate of 90%. A higher rate of partial responses occurred in patients whose tumors had low levels of MGMT expression (63%) compared to intermediate-high (17%) (p=0.19). Our results show that CAPTEM therapy is active in patients with NET including in previously treated patients and in those with poorly-differentiated histology. We observed a trend towards increased response rate, median PFS, and median OS in patients whose tumors had low MGMT protein expression., Competing Interests: CONFLICTS OF INTEREST The authors report no conflicts of interest.

The nucleation of glycine from aqueous supersaturated solution has been studied using non-photochemical laser-induced nucleation (NPLIN), ultrasound (sonocrystallization), and mechanical shock of sample vials. It was found that at higher supersaturation, samples were more susceptible to nucleation and produced more of the γ-glycine polymorph. The results are described in terms of a mechanism common to all three nucleation methods, involving the induction of cavitation events and pressure shockwaves. The switch in preference from α- to γ-glycine was observed to occur over a narrower range of supersaturation values for NPLIN. We attribute this to induction of cavitation events with higher energies, which result in higher localized pressures and supersaturations. Experiments on NPLIN using circularly versus linearly polarized light showed no evidence for binary polarization switching control of glycine polymorphism.

Musculoskeletal manifestations in chronic kidney disease (CKD) are the result of a series of complex alterations in mineral metabolism, which has been defined as chronic kidney disease - mineral and bone-related disorder (CKD-MBD). Biochemical assessment and, at times, bone biopsy remains the mainstay of disease assessment, however, radiological imaging is an important adjunct in evaluating disease severity. This review aims to illustrate the radiological features of CKD-MBD, such as secondary hyperparathyroidism, osteomalacia, adynamic bone disease, osteopenia, and extra-skeletal calcifications., (© 2017 Wiley Periodicals, Inc.)

Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB-COX2-prostaglandin E 2 (PGE 2 ) to suppress tumor necrosis factor-α (TNF-α) production by activated immune cells. Ex vivo conditioning of MSCs by WSS improved therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased apoptotic and M1-type activated microglia in the hippocampus. These results demonstrate that force provides critical cues to MSCs residing at the vascular interface which influence immunomodulatory and paracrine activity, and suggest the potential therapeutic use of force for MSC functional enhancement. Stem Cells 2017;35:1259-1272., (© 2017 AlphaMed Press.)

Leptospirosis is the most widespread zoonosis in the world and a neglected tropical disease estimated to cause severe infection in more than one million people worldwide every year that can be combated by effective immunization. However, no significant progress has been made on the leptospirosis vaccine since the advent of bacterins over 100 years. Although protective against lethal infection, particularly in animals, bacterin-induced immunity is considered short term, serovar restricted, and the vaccine can cause serious side effects. The urgent need for a new vaccine has motivated several research groups to evaluate the protective immune response induced by recombinant vaccines. Significant protection has been reported with several promising outer membrane proteins, including LipL32 and the leptospiral immunoglobulin-like proteins. However, efficacy was variable and failed to induce a cross-protective response or sterile immunity among vaccinated animals. As hundreds of draft genomes of all known Leptospira species are now available, this should aid novel target discovery through reverse vaccinology (RV) and pangenomic studies. The identification of surface-exposed vaccine candidates that are highly conserved among infectious Leptospira spp. is a requirement for the development of a cross-protective universal vaccine. However, the lack of immune correlates is a major drawback to the application of RV to Leptospira genomes. In addition, as the protective immune response against leptospirosis is not fully understood, the rational use of adjuvants tends to be a process of trial and error. In this perspective, we discuss current advances, the pitfalls, and possible solutions for the development of a universal leptospirosis vaccine.

In a seminal report on laser-induced nucleation in aqueous supersaturated solutions (Phys. Rev. Lett., 1996, 77, 3475) it was noted that needle-shaped crystals of urea were aligned with the direction of the electric field of the linearly polarized laser pulse. The results gave rise to a new mechanism for control of crystal nucleation involving alignment of solute molecules (optical Kerr effect) now commonly known as non-photochemical laser-induced nucleation (NPLIN). Recent theoretical and experimental work has cast doubts on the optical Kerr effect mechanism. In the present letter we present results from digital imaging of urea-crystal growth immediately following laser-induced nucleation. Analysis of the data shows no statistically significant correlation between crystal angle and direction of linear polarization. The results overturn a long-held result that has shaped theoretical and experimental studies of NPLIN.

Leptospirosis is a global zoonosis caused by pathogenic Leptospira spp. In this study, we characterized two Leptospira kirschneri serogroup Pomona serovar Mozdok isolates, one obtained from a dog and the other from a patient with severe leptospirosis, 4 years later. Histopathological analysis showed that both isolates caused severe tissue damage when used to infect hamsters. While L. kirschneri serogroup Pomona serovar Mozdok is endemic in animals in Europe, there is only one report of human leptospirosis in the literature. Although strains belonging to L. kirschneri serogroup Pomona have been identified in cases of human leptospirosis in Europe, serovar Mozdok has not yet been implicated. The 4-year interval between isolations and the fact that this is the first report of serovar Mozdok as the causative agent of human leptospirosis in the southern hemisphere, demonstrates its epidemiological importance to public health. Moreover, the presence of serovar Mozdok in Brazil has the potential to affect vaccine and diagnostic test development., (© The American Society of Tropical Medicine and Hygiene.)

The identification of potential vaccine candidates against leptospirosis remains a challenge. However, one such candidate is OmpL37, a potentially surface-exposed antigen that has the highest elastin-binding ability described to date, suggesting that it plays an important role in host colonization. In order to evaluate OmpL37's ability to induce a protective immune response, prime-boost, DNA and subunit vaccine strategies were tested in the hamster model of lethal leptospirosis. The humoral immune response was evaluated using an indirect ELISA test, and the cytokine profile in whole blood was determined by quantitative real-time PCR. Unlike the DNA vaccine, the administration of recombinant OmpL37 induced a strong IgG antibody response. When individually administrated, both formulations stimulated a TNF-α mediated inflammatory response. However, none of the OmpL37 formulations or vaccination strategies induced protective immunity. Further studies are required towards the identification of new vaccine targets against leptospirosis.

Background: Fibrosis is a common late complication of radiotherapy and/or surgical treatment for head and neck cancers. Fibrosis is difficult to quantify and formal methods of measure are not well recognized. The purpose of this review was to summarize the methods available to quantify neck fibrosis., Methods: A PubMed search of articles was carried out using key words "neck" and "fibrosis.", Results: Many methods have been used to assess fibrosis, however, there is no preferred methodology. Specific to neck fibrosis, most studies have relied upon hand palpation rating scales. Indentation and suction techniques have been used to mechanically quantify neck fibrosis. There is scope to develop applications of ultrasound, dielectric, bioimpedance, and MRI techniques for use in the neck region., Conclusion: Quantitative assessment of neck fibrosis is sought after in order to compare treatment regimens and improve quality of life outcomes in patients with head and neck cancer., (© 2014 Wiley Periodicals, Inc.)

Leptospira interrogans can infect a myriad of mammalian hosts, including humans (Bharti et al. , 2003; Ko et al. , 2009). Following acquisition by a suitable host, leptospires disseminate via the bloodstream to multiple tissues, including the kidneys, where they adhere to and colonize the proximal convoluted renal tubules (Athanazio et al. , 2008). Infected hosts shed large number of spirochetes in their urine and the leptospires can survive in different environmental conditions before transmission to another host. Differential gene expression by Leptospira spp. permits adaption to these new conditions. Here we describe a protocol for the cultivation of Leptospira interrogans within Dialysis Membrane Chambers (DMCs) implanted into the peritoneal cavities of Sprague-Dawley rats (Caimano et al. , 2014). This technique was originally developed to study mammalian adaption by the Lyme disease spirochete, Borrelia burgdorferi (Akins et al. , 1998; Caimano, 2005). The small pore size (8,000 MWCO) of the dialysis membrane tubing used for this procedure permits access to host nutrients but excludes host antibodies and immune effector cells. Given the physiological and environmental similarities between DMCs and the proximal convoluted renal tubule, we reasoned that the DMC model would be suitable for studying in vivo gene expression by L. interrogans . In a 20 to 30 min procedure, DMCs containing virulent leptospires are surgically-implanted into the rat peritoneal cavity. Nine to 11 days post-implantation, DMCs are explanted and organisms recovered. Typically, a single DMC yields ~10 9 mammalian host-adapted leptospires (Caimano et al. , 2014). In addition to providing a facile system for studying the transcriptional and physiologic changes pathogenic L. interrogans undergo within the mammal, the DMC model also provides a rationale basis for selecting new targets for mutagenesis and the identification of novel virulence determinants. Caution: Leptospira interrogans is a BSL-2 level pathogen and known to be excreted in the urine of infected animals. Animals should be handled and disposed of using recommended Animal Biosafety Levels (ABSL) for infectious agents using vertebrate animal guidelines. Note: All protocols using live animals must conform to governmental regulations regarding the care and use of laboratory animals. The success of this protocol is dependent on the proper use of aseptic techniques during all stages of both dialysis membrane chamber preparation and animal surgery.

A detailed experimental study of laser-induced nucleation (LIN) of carbon dioxide (CO2) gas bubbles is presented. Water and aqueous sucrose solutions supersaturated with CO2 were exposed to single nanosecond pulses (5 ns, 532 nm, 2.4-14.5 MW cm(-2)) and femtosecond pulses (110 fs, 800 nm, 0.028-11 GW cm(-2)) of laser light. No bubbles were observed with the femtosecond pulses, even at high peak power densities (11 GW cm(-2)). For the nanosecond pulses, the number of bubbles produced per pulse showed a quadratic dependence on laser power, with a distinct power threshold below which no bubbles were observed. The number of bubbles observed increases linearly with sucrose concentration. It was found that filtering of solutions reduces the number of bubbles significantly. Although the femtosecond pulses have higher peak power densities than the nanosecond pulses, they have lower energy densities per pulse. A simple model for LIN of CO2 is presented, based on heating of nanoparticles to produce vapor bubbles that must expand to reach a critical bubble radius to continue growth. The results suggest that non-photochemical laser-induced nucleation of crystals could also be caused by heating of nanoparticles.

Toxocariasis is a neglected zoonosis caused by the nematodes Toxocara canis and Toxocara cati. This disease is widespread in many countries, reaching high prevalence independently of the economic conditions. However, the true number of cases of toxocariasis is likely to be underestimated owing to the lack of adequate surveillance programs. Although some diagnostic tests are available, their sensitivity and specificity need to be improved. In addition, treatment options for toxocariasis are limited and are non-specific. Toxocariasis is listed as one of the five most important neglected diseases by the CDC. This review presents recent advances related to the control of toxocariasis, including new immunodiagnostics, therapies, and drug formulations, as well as novel interventions using DNA vaccines, immunomodulators, and probiotics., (Copyright © 2014 Elsevier Ltd. All rights reserved.)