Genomic sequencing research in pediatric cancer care: Decision making, attitudes, and perceived utility among adolescents and young adults and their parents.

PURPOSE: Professional guidelines recommend engaging adolescents and young adults (AYAs) in medical decision making (DM), including whether to undergo genomic sequencing (GS). We explored DM around GS and attitudes after return of GS results among a diverse group of AYAs with cancer and their parents. METHODS: We surveyed AYAs with cancer (n = 75) and their parents (n = 52) 6 months after receiving GS results through the Texas KidsCanSeq study. We analyzed AYAs' DM role in GS research enrollment and their satisfaction with that role. We compared AYAs' and parents' self-reported understanding of, attitudes toward, and perceived utility of the AYA's GS results. RESULTS: Most AYAs reported equally sharing DM with their parents (55%) or leading DM (36%) about GS research. Compared with their cancer care DM role, 56% of AYAs reported the same level of involvement in GS research DM, whereas 32% were more involved, and 13% were less involved (P = .011). AYAs were satisfied (99%) with their DM role regarding GS study participation. AYAs and parents had similar self-reported understanding of, attitudes toward, and perceived utility of the GS results. CONCLUSION: Our results support engaging AYAs in DM about GS research and provide insights into AYAs' DM preferences and positive attitudes toward GS.

Psychosocial services for pediatric oncology patients in low- and middle-income countries from health care providers' perspectives: A survey-based report from the SIOP Global Health Network Psychosocial Working Group.

OBJECTIVES: While pediatric cancer survival rates have improved in high-income countries, they remain much lower in low- and middle-income countries (L/MICs). While much focus in recent years has been on remediating the survivorship gap, less is known about the psychosocial needs and availability of psychosocial services for this population. METHODS: A questionnaire was created by the SIOP Global Health Network Psychosocial Working Group to assess psychosocial needs and services in L/MIC. The questionnaire was distributed to pediatric oncology professionals, both in-person at the SIOP Annual Congress in Lyon (2019) conference and then electronically. Individuals not part of SIOP were also invited to participate via social media posts. RESULTS: Sixty-six respondents from 31 countries completed the questionnaire. The majority of participants were physicians, followed by nurses. Participants from low- and lower-middle-income countries (L/LMICs) perceived patients as having higher rates of anxiety and caregivers as having higher rates of depression as compared to those in upper-middle-income countries (UMICs). Across all L/MICs represented, 85% of physicians reported that psychosocial issues sometimes, frequently, or always affect their clinical obligations. Participants reflected on the availability of professionals who treat mental health concerns; the availability of social workers, psychologists, and non-professional volunteers differed significantly between L/LMICs and UMICs. Treatment abandonment and myths/disinformation were highlighted as the most pressing psychosocial priorities. CONCLUSION: Our study highlights pediatric oncology providers' perceptions of psychosocial concerns. Based on responses, proposals for minimum standards of care are made, as well as the importance of training existing providers and funding additional psychosocially-focused professionals.

Pediatric Consultation-Liaison Psychology: Insights and Lessons Learned During the COVID-19 Pandemic.

COVID-19 has presented a variety of challenges to the provision of psychology services. In the first month of the pandemic, pediatric consultation-liaison (CL) psychologists reported significant changes in methodology of service delivery (Steinberg et al. in Clin Pract Pediatr Psychol 9:1, 2020). To better understand how and if these changes persisted, as well as other emerging trends, a follow-up study examined changes and challenges six months into the pandemic. An anonymous questionnaire assessed topics related to pediatric CL psychology including practice changes, perception of changes, and institutional support. The questionnaire was sent to the APA Society of Pediatric Society's special interest group listservs. Thirty responses were analyzed. Quantitative results showed participants' beliefs that telemedicine is equally efficacious to in-person services for outpatient psychological care, but less effective for inpatient care. Participants reported their perception of how institutions supported their safety, psychology trainee safety and training goals, and patient care. Qualitative results demonstrated that most psychologists experienced changes related to their dynamics with medical teams, which included changes in team efficiency, workload, transition, and team collaboration.

A randomized controlled trial of transition from insulin pump to multiple daily injections using insulin degludec.

AIM: To evaluate two methods of transition from an insulin pump to multiple daily injections (MDI) using long-acting insulin degludec (IDeg). MATERIALS AND METHODS: After a 1-week run-in period, adults with type 1 diabetes for longer than 1 year and HbA1c 48-69 mmol/mol (6.5%-8.5%), who had been using an insulin pump at least for 6 months, were randomly transitioned to either standard of care (discontinued insulin pump and started IDeg in 1:1 dose) or overlap (IDeg 1:1 at pump basal dose, but pump continued for the first 48 hours with a gradual basal reduction; 50% from 0-24 hours, 75% from 24-48 hours and then pump discontinued). Participants used blinded Dexcom G6 and the IDeg dose was not changed during the trial. Primary (% time above 180 mg/dL) and secondary (% time in 70-180 mg/dL and below 70 mg/dL) outcomes were compared between the two groups during 7 days of randomization. RESULTS: Age, gender, diabetes duration and basal/bolus insulin doses were similar between patients randomized to standard of care (n = 17) or overlap (n = 13) transition. Compared with overlap transition, the standard of care group spent 4.8% more time in hyperglycaemia (least square mean 4.8% [95% CI -3.3%, 12.9%]) and 5.3% less time in range (-5.3% [-12.6%, -2.0%]), without a significant difference in hypoglycaemia (0.5% [-2.3%,3.4%]). No treatment-related adverse events were noted in either group. CONCLUSION: The overlap transition method may result in a significant improvement in time-in-range without increasing hypoglycaemia during the first week of transition from an insulin pump to MDI using IDeg in adults with type 1 diabetes.

Short report: sticks and stones may break my bones, but words can also hurt me: understanding language interpreters' perceptions of stress/growth and needs in a pediatric medical setting.

An increased focus on quality, trauma-informed patient care also warrants examination of providers' experiences of stress in medical settings. However, little is known about language interpreters' experiences of stress in the pediatric hospital setting, despite their involvement in acute and difficult patient encounters. This pilot study evaluated language interpreters' experiences and perceptions of stress in a large children's hospital. Descriptive and qualitative analyses, using a novel survey measure of interpreters' experiences, were performed to evaluate language interpreters' experiences with stressful patient encounters and identification of available and desired supports. All interpreters surveyed endorsed experiencing stress during challenging patient encounters in the hospital, though the majority also identified positive changes to their worldview as a result of their work. Results highlighted interpreters' strategies to cope with stress and perceived institutional needs to manage stressful encounters. Interpreters' experiences of stress in the pediatric hospital underscores needs for prevention and intervention efforts aimed at helping interpreters manage job-related stress. Preliminary, trauma-informed recommendations for working with and supporting interpreters are proposed.

Functional properties of the retinal glutamate transporters GLT-1c and EAAT5.

In the mammalian retina, glutamate uptake is mediated by members of a family of glutamate transporters known as "excitatory amino acid transporters (EAATs)." Here we cloned and functionally characterized two retinal EAATs from mouse, the GLT-1/EAAT2 splice variant GLT-1c, and EAAT5. EAATs are glutamate transporters and anion-selective ion channels, and we used heterologous expression in mammalian cells, patch-clamp recordings and noise analysis to study and compare glutamate transport and anion channel properties of both EAAT isoforms. We found GLT-1c to be an effective glutamate transporter with high affinity for Na(+) and glutamate that resembles original GLT-1/EAAT2 in all tested functional aspects. EAAT5 exhibits glutamate transport rates too low to be accurately measured in our experimental system, with significantly lower affinities for Na(+) and glutamate than GLT-1c. Non-stationary noise analysis demonstrated that GLT-1c and EAAT5 also differ in single-channel current amplitudes of associated anion channels. Unitary current amplitudes of EAAT5 anion channels turned out to be approximately twice as high as single-channel amplitudes of GLT-1c. Moreover, at negative potentials open probabilities of EAAT5 anion channels were much larger than for GLT-1c. Our data illustrate unique functional properties of EAAT5, being a low-affinity and low-capacity glutamate transport system, with an anion channel optimized for anion conduction in the negative voltage range.

Allosteric modulation of an excitatory amino acid transporter: the subtype-selective inhibitor UCPH-101 exerts sustained inhibition of EAAT1 through an intramonomeric site in the trimerization domain.

In the present study, the mechanism of action and molecular basis for the activity of the first class of selective inhibitors of the human excitatory amino acid transporter subtype 1 (EAAT1) and its rodent ortholog GLAST are elucidated. The previously reported specificity of UCPH-101 and UCPH-102 for EAAT1 over EAAT2 and EAAT3 is demonstrated to extend to the EAAT4 and EAAT5 subtypes as well. Interestingly, brief exposure to UCPH-101 induces a long-lasting inactive state of EAAT1, whereas the inhibition exerted by closely related analogs is substantially more reversible in nature. In agreement with this, the kinetic properties of UCPH-101 unblocking of the transporter are considerably slower than those of UCPH-102. UCPH-101 exhibits noncompetitive inhibition of EAAT1, and its binding site in GLAST has been delineated in an elaborate mutagenesis study. Substitutions of several residues in TM3, TM4c, and TM7a of GLAST have detrimental effects on the inhibitory potency and/or efficacy of UCPH-101 while not affecting the pharmacological properties of (S)-glutamate or the competitive EAAT inhibitor TBOA significantly. Hence, UCPH-101 is proposed to target a predominantly hydrophobic crevice in the "trimerization domain" of the GLAST monomer, and the inhibitor is demonstrated to inhibit the uptake through the monomer that it binds to exclusively and not to affect substrate translocation through the other monomers in the GLAST trimer. The allosteric mode of UCPH-101 inhibition underlines the functional importance of the trimerization domain of the EAAT and demonstrates the feasibility of modulating transporter function through ligand binding to regions distant from its "transport domain."

Mutating a conserved proline residue within the trimerization domain modifies Na+ binding to excitatory amino acid transporters and associated conformational changes.

Excitatory amino acid transporters (EAATs) are crucial for glutamate homeostasis in the mammalian central nervous system. They are not only secondary active glutamate transporters but also function as anion channels, and different EAATs vary considerably in glutamate transport rates and associated anion current amplitudes. A naturally occurring mutation, which was identified in a patient with episodic ataxia type 6 and that predicts the substitution of a highly conserved proline at position 290 by arginine (P290R), was recently shown to reduce glutamate uptake and to increase anion conduction by hEAAT1. We here used voltage clamp fluorometry to define how the homologous P259R mutation modifies the functional properties of hEAAT3. P259R inverts the voltage dependence, changes the sodium dependence, and alters the time dependence of hEAAT3 fluorescence signals. Kinetic analysis of fluorescence signals indicate that P259R decelerates a conformational change associated with sodium binding to the glutamate-free mutant transporters. This alteration in the glutamate uptake cycle accounts for the experimentally observed changes in glutamate transport and anion conduction by P259R hEAAT3.

A new Cyrtodactylus (Squamata: Gekkonidae) from Khanh Hoa Province, southern Vietnam.

We describe a new species of the genus Cyrtodactylus from southern Vietnam, based on morphological and molecular datasets. Cyrtodactylus cucdongensis sp. nov. is described on the basis of seven specimens collected from Cuc Dong Cape, Khanh Hoa Province. The new species can be distinguished from the remaining bent-toed geckos by a combination of the following characters: maximum SVL 65.9 mm; 16-19 dorsal tubercle rows; 41-44 ventral scales at midbody; 5 or 6 precloacal pores in males, 4-6 pitted precloacal scales in females; no femoral pores; 6-13 enlarged precloacal scales; 5-9 enlarged femoral scales; no transversally enlarged subcaudals; dorsal pattern consisting of irregular dark bands. This is the 33rd species of Cyrtodactylus known from Vietnam.

Effects of Education, Nutrition, and Psychology on Preventing the Female Athlete Triad.

The female athlete triad is a syndrome occurring in young female athletes defined by menstrual dysfunction, decreased energy availability (EA), and low bone mineral density (BMD). Although the triad includes these three conditions, not all three need to occur simultaneously for the diagnosis to be made. The goal of this review is to analyze published research on the female athlete triad and determine prevention methods in athletics. A review of 23 published sources using the PubMed database identified key recommendations, including education resources, psychological factors, and nutrition. It is recommended that athletes, parents, coaches, and healthcare professionals should learn about the risk factors, warning signs, and diagnosis for better prevention. Research revealed that eating disorders, self-esteem issues, and coach-athlete relationships should be evaluated and potentially managed with counseling. Finally, nutritional recommendations included maintaining EA, providing nutritional counseling, and proper nutritional education. Early intervention with proper education, psychological support, and nutritional management are vital to preventing the onset of the female athlete triad.

The Use of Platelet-Rich Plasma and Stem Cell Injections in Musculoskeletal Injuries.

Injuries to the musculoskeletal (MSK) system can have a significant impact on an individual's activities of daily living, as this multifunctional unit is associated with physical movement. Treatment of MSK injuries often involves corticosteroid injections, supplements, pharmaceutical agents, and/or surgery. While these approaches have been shown to be effective for some patients over both the short and long term, they can be associated with limited relief, adverse effects, and/or decreases in activities of daily living. An unmet need exists to develop and/or implement more effective treatment approaches for MSK injuries. Treatment options being explored include platelet-rich plasma (PRP) and stem cell injections. This review outlines the current state of research evaluating PRP and stem cell injections in the treatment of various MSK injuries. A literature search was conducted using the PubMed database to identify the relevant published articles related to the use of PRP and/or stem cell injections for the treatment of MSK and cartilage injuries. PRP and stem cell injections have been shown to improve an individual's quality of life (QOL) and are associated with fewer side effects as compared to invasive standards of care in multiple MSK injuries such as plantar fasciitis, Achilles tendinopathy, acute muscle and tendon tears, ligament injuries, chondral and medial collateral ligament (MCL) knee injuries and arthritis, rotator cuff lesions, and avascular femoral necrosis. Specifically, these studies on PRP and stem cell injections suggest that both approaches are associated with a quicker return to activities of daily living while providing longer lasting relief without significant adverse events. The studies reviewed demonstrated PRP and stem cell approaches to be effective and safe for the treatment of certain MSK injuries, but as standardized protocols were not utilized across studies in the discussion of similar injuries, it was therefore difficult to compare their efficacy and safety. As such, further research is warranted to establish standardized research protocols across MSK injury studies to gain further insight into the efficacy, safety, and durability of PRP and stem cell injections.

The Role of Pediatric Psychologists in Critical Care: Lessons Learned and Future Directions in Integrating Mental Health Care Into PICUs.

Pediatric psychologists are essential staff in the PICU. Their role in caring for critically ill children aligns with clinical practice guidelines for the mental health care needs of this population of patients. This article highlights the role of pediatric psychology in the PICU through illustrative case examples. We discuss lessons learned and future directions for the development and provision of mental health services in PICUs. We address relevant ways for critical care providers to understand the importance of evidence-based psychological care and advocate for the inclusion of psychologists on multidisciplinary PICU teams. As the critical care field continues to focus on an improved understanding of post-intensive care syndrome in pediatrics and the psychological needs of critical care patients, it will be important to consider the vital roles of psychologists and to advocate for improved integration of mental health care in PICUs.

The association between reduced calf and mid-arm circumferences and ICU mortality in critically ill COVID-19 patients.

BACKGROUND & AIMS: Patients with COVID-19 are at a high risk of malnutrition caused by inflammatory syndrome and persistent hypermetabolism, which may affect clinical outcomes. This study aimed to evaluate the changes in nutritional status indicators between two time points of nutritional assessments of COVID-19 patients during their stay in the intensive care unit (ICU). Moreover, the study also assessed the association of nutritional status with ICU mortality. METHODS: This cohort study included retrospective data of adult patients admitted to a public hospital ICU in southern Brazil, between March and September 2020. These participants with confirmed COVID-19 diagnosis received nutritional assessment within the first 72 h after ICU admission. The anthropometric measurements collected included mid-arm circumference (MAC) and calf circumference (CC). The percentage (%) of MAC adequacy was calculated, and values < 50th percentile for sex and age were considered low. CC values of ≤33 cm for women and ≤34 cm for men were indicative of reduced muscle mass. Data on the date of discharge from the ICU and mortality outcome were collected. RESULTS: A total of 249 patients were included (53.4% men, 62.2 ± 13.9 years of age, SOFA severity score 9.6 ± 3.5). Of these, 22.7 and 39.1% had reduced MAC and CC at ICU admission, respectively. In these participants, weight, MAC, CC, and % MAC decreased significantly from the first to second nutritional assessment (p < 0.05), but there was no significant difference between survivors and non-survivors. Patients with reduced CC (HR = 2.63; 95% CI 1.65-4.18) or reduced MAC (HR = 2.11; 95% CI 1.37-3.23) at the first nutritional assessment had approximately twice the risk of death in the ICU than those with normal CC and normal MAC, regardless of the severity assessed by the SOFA score and age. CONCLUSION: Reduced MAC and CC values were identified in approximately 20 and 40% of COVID-19 patients admitted to the ICU, respectively. Additionally, these indicators of nutritional depletion were associated with an approximately 2-fold increase in the risk of ICU mortality. A significant reduction in anthropometric indicators during the first weeks of ICU stay confirmed the deterioration of nutritional status in these patients, although this was not associated with mortality.

Psychometric properties of the 52-, 25-, and 10-item English and Spanish versions of the Social Problem-Solving Inventory-Revised.

Objective: The Social Problem-Solving Inventory-Revised (SPSI-R) is a widely used instrument to assess problem-solving ability. This study examined the factor structure of the 52-, 25-, and 10-item versions of the SPSI-R and assessed factorial invariance across English- and Spanish-speaking participants. In addition, the internal consistency, test-retest reliability and sensitivity to detect change in problem-solving skills over time were assessed across the three different versions of the SPSI-R. Methods: Data from three randomized controlled trials, in which caregivers of children with cancer (N = 1,069) were assigned to either a problem-solving skills intervention (N = 728) or a control condition (N = 341), were combined. The SPSI-R was administered at baseline (T1) and immediately post intervention (T2). Reliability and multigroup analyses were performed with confirmatory factor analysis (CFA). Sensitivity to change analyses were performed using repeated measures ANOVA. Results: Confirmatory factor analysis at T1 showed good fit statistics and internal consistency for the 52- and the 25-item versions, but not for the 10-item version. Factorial invariance was demonstrated across time (T1-T2) and language (Spanish-English) for both the 52- and 25-item versions. Adequate sensitivity to change over time was shown. Conclusion: The 52- and 25-item versions of the SPSI-R appear reliable and valid for assessment of problem-solving skills in English- and Spanish-speaking caregivers of children with newly diagnosed cancer. The 25-item SPSI-R can be used as a short version measuring problem-solving ability; the 10-item version cannot be considered a reliable measure for this population.

Psychological and Psychiatric Comorbidities in Youth with Serious Physical Illness.

An estimated one in six children in the United States suffers from a mental disorder, including mood, anxiety, or behavioral disorders. This rate is even higher in children with chronic medical illness. This manuscript provides a concise review of the symptoms that comprise mental conditions often observed in children with chronic illness or at the end of life. It further provides some guidance to help clinicians distinguish normative from pathological presentations. Evidence-based psychotherapy interventions, potentially applicable to the acute inpatient setting, are briefly summarized. Broad recommendations are made regarding both psychotherapeutic as well as pharmacotherapeutic interventions, with a review of common or serious medication side effects. Finally, delirium recognition and management are summarized.

Accuracy of Patient-Specific Drill Guide Template for Bilateral C1-C2 Laminar Screw Placement: A Cadaveric Study.

OBJECTIVE: We sought to evaluate the accuracy of using patient-specific drill guides to place bilateral laminar screws in C1 and C2. METHODS: Nine cervical specimens (8 males; mean age: 66.6 [56-73]) with the occiput attached (C0-C3) were used in this study. Preoperative computed tomography (CT) scans were used to create digital anatomic models for templating and guide creation. A total of 36 screws were placed with the aid of 3-dimensional printed, patient-specific guides (2 screws at C1 and C2). Postoperative CT scans were performed following screw insertion. The planned and actual trajectories were compared using preoperative and postoperative imaging based on the angular and entry point deviation. After screw placement and postoperative imaging, each specimen was dissected and performed a visual inspection for breaches. RESULTS: No breaches or violations were observed on postprocedural CT and visual inspection. The average variation of the entry point in the X, Y, and Z axes was 0.3 ± 0.28, 0.41 ± 0.38, and 0.29 ± 0.24, respectively. No statistically significant difference (P > 0.05) was observed between the planned and obtained entry points. There was no significant difference (P > 0.05) in the deviation analysis between the planned and obtained angles in the axial and coronal planes. CONCLUSIONS: The study demonstrates that patient-specific drill guides allow for accurate C1 and C2 bilateral laminar screw placement, with a low risk of cortical breach.

Lumbar degenerative spondylolisthesis: factors associated with the decision to fuse.

BACKGROUND CONTEXT: The indication to perform a fusion and decompression surgery as opposed to decompression alone for lumbar degenerative spondylolisthesis (LDS) remains controversial. A variety of factors are considered when deciding on whether to fuse, including patient demographics, radiographic parameters, and symptom presentation. Likely surgeon preference has an important influence as well. PURPOSE: The aim of this study was to assess factors associated with the decision of a Canadian academic spine surgeon to perform a fusion for LDS. STUDY DESIGN/SETTING: This study is a retrospective analysis of patients prospectively enrolled in a multicenter Canadian study that was designed to evaluate the assessment and surgical management of LDS. PATIENT SAMPLE: Inclusion criteria were patients with: radiographic evidence of LDS and neurogenic claudication or radicular pain, undergoing posterior decompression alone or posterior decompression and fusion, performed in one of seven, participating academic centers from 2015 to 2019. OUTCOME MEASURES: Patient demographics, patient-rated outcome measures (Oswestry Disability Index [ODI], numberical rating scale back pain and leg pain, SF-12), and imaging parameters were recorded in the Canadian Spine Outcomes Research Network (CSORN) database. Surgeon factors were retrieved by survey of each participating surgeon and then linked to their specific patients within the database. METHODS: Univariate analysis was used to compare patient characteristics, imaging measures, and surgeon variables between those that had a fusion and those that had decompression alone. Multivariate backward logistic regression was used to identify the best combination of factors associated with the decision to perform a fusion. RESULTS: This study includes 241 consecutively enrolled patients receiving surgery from 11 surgeons at 7 sites. Patients that had a fusion were younger (65.3±8.3 vs. 68.6±9.7 years, p=.012), had worse ODI scores (45.9±14.7 vs. 40.2±13.5, p=.007), a smaller average disc height (6.1±2.7 vs. 8.0±7.3 mm, p=.005), were more likely to have grade II spondylolisthesis (31% vs. 14%, p=.008), facet distraction (34% vs. 60%, p=.034), and a nonlordotic disc angle (26% vs. 17%, p=.038). The rate of fusion varied by individual surgeon and practice location (p<.001, respectively). Surgeons that were fellowship trained in Canada more frequently fused than those who fellowship trained outside of Canada (76% vs. 57%, p=.027). Surgeons on salary fused more frequently than surgeons remunerated by fee-for-service (80% vs. 64%, p=.004). In the multivariate analysis the clinical factors associated with an increased odds of fusion were decreasing age, decreasing disc height, and increasing ODI score; the radiographic factors were grade II spondylolisthesis and neutral or kyphotic standing disc type; and the surgeon factors were fellowship location, renumeration type and practice region. The odds of having a fusion surgery was more than two times greater for patients with a grade II spondylolisthesis or neutral and/or kyphotic standing disc type (opposed to lordotic standing disc type). Patients whose surgeon completed their fellowship in Canada, or whose surgeon was salaried (opposed to fee-for-service), or whose surgeon practiced in western Canada had twice the odds of having fusion surgery. CONCLUSIONS: The decision to perform a fusion in addition to decompression for LDS is multifactorial. Although patient and radiographic parameters are important in the decision-making process, multiple surgeon factors are associated with the preference of a Canadian spine surgeon to perform a fusion for LDS. Future work is necessary to decrease treatment variability between surgeons and help facilitate the implementation of evidence-based decision making.

Signals of recent spatial expansions in the grey mouse lemur (Microcebus murinus).

BACKGROUND: Pleistocene events have shaped the phylogeography of many taxa worldwide. Their genetic signatures in tropical species have been much less explored than in those living in temperate regions. We analysed the genetic structure of a Malagasy primate species, a mouse lemur with a wide distribution (M. murinus), in order to investigate such phylogeographic processes on a large tropical island. We also evaluated the effects of anthropogenic pressures (fragmentation/deforestation) and natural features (geographic distance, rivers) on genetic structure in order to complement our understanding of past and present processes of genetic differentiation. RESULTS: The analysis of the mitochondrial D-loop sequences of 195 samples from 15 study sites (10 from a continuous forest and five from isolated forest fragments) from two adjacent Inter-River-Systems (IRSs) revealed that forest fragmentation and the river restrict gene flow, thereby leading to an increased genetic differentiation between populations beyond the effect of isolation-by-distance. Demographic simulations detected signals of two successive spatial expansions that could be preliminarily dated to the late Pleistocene and early Holocene. The haplotype network revealed geographic structure and showed deep molecular divergences within and between the IRSs that would be congruent with a two-step colonization scenario. CONCLUSIONS: This study supports the hypothesis of a relatively recent spatial expansion of the grey mouse lemur in northwestern Madagascar, which may also explain why this taxon, in contrast to its congeners, has not yet undergone allopatric speciation in the studied area and possibly across its presently wide range.

Blackout Versus Pass Out in Allegations of Alcohol-involved Sexual Assault: Why Knowing the Difference Matters.

It is common for not only laypersons but also courts, witnesses, attorneys, and even some experts involved in a criminal sexual assault investigation to confuse the terms "blackout" and "pass out" when referring to the memory, consciousness, and other behavioral ramifications of alcohol intoxication. A typical alcohol-involved sexual assault allegation often includes the partial or total absence of memory for events of the alleged incident. The etiology and behavioral presentations of the types of alcohol-induced memory deficiency evidenced are not all created equal and understanding the differences is crucial to understanding the reasonableness of the potential perceptions or misperceptions of an accused. By improving our understanding of these terms, we can assist the legal process with proper and more accurate history gathering and documentation if we become a party to such an investigation.

Iron Pathways and Iron Chelation Approaches in Viral, Microbial, and Fungal Infections.

Iron is an essential element required to support the health of organisms. This element is critical for regulating the activities of cellular enzymes including those involved in cellular metabolism and DNA replication. Mechanisms that underlie the tight control of iron levels are crucial in mediating the interaction between microorganisms and their host and hence, the spread of infection. Microorganisms including viruses, bacteria, and fungi have differing iron acquisition/utilization mechanisms to support their ability to acquire/use iron (e.g., from free iron and heme). These pathways of iron uptake are associated with promoting their growth and virulence and consequently, their pathogenicity. Thus, controlling microorganismal survival by limiting iron availability may prove feasible through the use of agents targeting their iron uptake pathways and/or use of iron chelators as a means to hinder development of infections. This review will serve to assimilate findings regarding iron and the pathogenicity of specific microorganisms, and furthermore, find whether treating infections mediated by such organisms via iron chelation approaches may have potential clinical benefit.