The association between overuse and musculoskeletal injuries and the female athlete triad in Division I collegiate athletes.

INTRODUCTION: Although the female athlete triad (Triad) has been associated with increased risk of bone-stress injuries (BSIs), limited research among collegiate athletes has addressed the associations between the Triad and non-BSI injuries. OBJECTIVE: To elucidate the relationship between Triad and both BSI and non-BSI in female athletes. DESIGN: Retrospective cohort study. SETTING: Primary and tertiary care student athlete clinic. PARTICIPANTS: National Collegiate Athletic Association Division I female athletes at a single institution. INTERVENTION: Participants completed a pre-participation questionnaire and dual-energy x-ray absorptiometry, which was used to generate a Triad cumulative risk assessment score (Triad score). The number of overuse musculoskeletal injuries that occurred while the athletes were still competing collegiately were identified through chart review. MAIN OUTCOME MEASURE: BSI and non-BSI were treated as count variables. The association between BSI, non-BSI, and Triad score was measured using Poisson regression to calculate rate ratios. RESULTS: Of 239 athletes, 43% of athletes (n = 103) sustained at least one injury. Of those, 40% (n = 95) sustained at least one non-BSI and 10% (n = 24) sustained at least one BSI over an average follow-up 2.5 years. After accounting for sport type (non-lean, runner, other endurance sport, or other lean advantage sport) and baseline age, we found that every additional Triad score risk point was associated with a significant 17% increase in the rate of BSI (rate ratio [RR] 1.17, 95% confidence interval [CI] 1.03-1.33; p = .016). However, Triad score was unrelated to non-BSI (1.00, 95% CI 0.91-1.11; p = .99). Compared with athletes in non-lean sports (n = 108), athletes in other lean advantage sports (n = 30) had an increased rate of non-BSI (RR: 2.09, p = .004) whereas distance runners (n = 46) had increased rates of BSI (RR: 7.65, p < .001) and non-BSI (RR: 2.25, p < .001). CONCLUSIONS: Higher Triad score is associated with an increased risk of BSI but not non-BSI in collegiate athletes.

The stabilized supralinear network accounts for the contrast dependence of visual cortical gamma oscillations.

When stimulated, neural populations in the visual cortex exhibit fast rhythmic activity with frequencies in the gamma band (30-80 Hz). The gamma rhythm manifests as a broad resonance peak in the power-spectrum of recorded local field potentials, which exhibits various stimulus dependencies. In particular, in macaque primary visual cortex (V1), the gamma peak frequency increases with increasing stimulus contrast. Moreover, this contrast dependence is local: when contrast varies smoothly over visual space, the gamma peak frequency in each cortical column is controlled by the local contrast in that column's receptive field. No parsimonious mechanistic explanation for these contrast dependencies of V1 gamma oscillations has been proposed. The stabilized supralinear network (SSN) is a mechanistic model of cortical circuits that has accounted for a range of visual cortical response nonlinearities and contextual modulations, as well as their contrast dependence. Here, we begin by showing that a reduced SSN model without retinotopy robustly captures the contrast dependence of gamma peak frequency, and provides a mechanistic explanation for this effect based on the observed non-saturating and supralinear input-output function of V1 neurons. Given this result, the local dependence on contrast can trivially be captured in a retinotopic SSN which however lacks horizontal synaptic connections between its cortical columns. However, long-range horizontal connections in V1 are in fact strong, and underlie contextual modulation effects such as surround suppression. We thus explored whether a retinotopically organized SSN model of V1 with strong excitatory horizontal connections can exhibit both surround suppression and the local contrast dependence of gamma peak frequency. We found that retinotopic SSNs can account for both effects, but only when the horizontal excitatory projections are composed of two components with different patterns of spatial fall-off with distance: a short-range component that only targets the source column, combined with a long-range component that targets columns neighboring the source column. We thus make a specific qualitative prediction for the spatial structure of horizontal connections in macaque V1, consistent with the columnar structure of cortex.

Response sub-additivity and variability quenching in visual cortex.

Sub-additivity and variability are ubiquitous response motifs in the primary visual cortex (V1). Response sub-additivity enables the construction of useful interpretations of the visual environment, whereas response variability indicates the factors that limit the precision with which the brain can do this. There is increasing evidence that experimental manipulations that elicit response sub-additivity often also quench response variability. Here, we provide an overview of these phenomena and suggest that they may have common origins. We discuss empirical findings and recent model-based insights into the functional operations, computational objectives and circuit mechanisms underlying V1 activity. These different modelling approaches all predict that response sub-additivity and variability quenching often co-occur. The phenomenology of these two response motifs, as well as many of the insights obtained about them in V1, generalize to other cortical areas. Thus, the connection between response sub-additivity and variability quenching may be a canonical motif across the cortex.

Durability of deep transcranial magnetic stimulation for veterans with treatment resistant depression with comorbid suicide risk and PTSD symptoms.

Evidence supports transcranial magnetic stimulation (TMS) as an effective treatment for symptoms of depression and PTSD; however, there has been limited investigation into the durability of symptoms reduction. The Hampton Veterans Affairs Medical Center's (HVAMC) rTMS clinic used H-coil for dTMS for Veterans with treatment-resistant depression and tracked symptomology at multiple times points up to six months post-treatment. Veterans underwent 30 session of dTMS treatment using the Hesed coil (H1 coil). The PHQ-9, PCL-5, and BSS were administered to Veterans at four time points: pretreatment, post-treatment, three months after treatment, and six months after treatment. In aggregate, there were clinically significant reductions in symptoms of depression (43.47%), PTSD (44.14%) and suicidal ideation (54.02%) at the six month follow-up relative to pretreatment. Results provide evidence of the impact and durability of dTMS on symptoms of MDD, PTSD, and suicidal ideation among Veterans with treatment-resistant depression.

Strategies to improve the quality and usefulness of mental health trials in humanitarian settings.

A striking rise in the number of people affected by humanitarian crises has led to an increase in mental health and psychosocial support interventions to reduce the psychological effects of such crises. In a parallel trend, researchers have brought increased methodological rigour to their evaluation of these interventions. However, several methodological issues still constrain the quality and real-world relevance of the existing evidence base. We examine five core challenges in randomised controlled trials of mental health and psychosocial support interventions with conflict-affected and disaster-affected populations. These challenges are: translating intervention effects into metrics of real-world significance; giving adequate consideration to the selection and monitoring of control conditions; following rigorous processes to ensure outcome measures are culturally appropriate and psychometrically sound; ensuring and monitoring implementation variables, including fidelity, exposure, participant engagement, and the competence of implementation staff; and assessing mechanisms of change.

Mechanisms underlying reshuffling of visual responses by optogenetic stimulation in mice and monkeys.

The ability to optogenetically perturb neural circuits opens an unprecedented window into mechanisms governing circuit function. We analyzed and theoretically modeled neuronal responses to visual and optogenetic inputs in mouse and monkey V1. In both species, optogenetic stimulation of excitatory neurons strongly modulated the activity of single neurons yet had weak or no effects on the distribution of firing rates across the population. Thus, the optogenetic inputs reshuffled firing rates across the network. Key statistics of mouse and monkey responses lay on a continuum, with mice/monkeys occupying the low-/high-rate regions, respectively. We show that neuronal reshuffling emerges generically in randomly connected excitatory/inhibitory networks, provided the coupling strength (combination of recurrent coupling and external input) is sufficient that powerful inhibitory feedback cancels the mean optogenetic input. A more realistic model, distinguishing tuned visual vs. untuned optogenetic input in a structured network, reduces the coupling strength needed to explain reshuffling.

Localized uplift, widespread subsidence, and implications for sea level rise in the New York City metropolitan area.

Regional relative sea level rise is exacerbating flooding hazards in the coastal zone. In addition to changes in the ocean, vertical land motion (VLM) is a driver of spatial variation in sea level change that can either diminish or enhance flood risk. Here, we apply state-of-the-art interferometric synthetic aperture radar and global navigation satellite system time series analysis to estimate velocities and corresponding uncertainties at 30-m resolution in the New York City metropolitan area, revealing VLM with unprecedented detail. We find broad subsidence of 1.6 mm/year, consistent with glacial isostatic adjustment to the melting of the former ice sheets, and previously undocumented hot spots of both subsidence and uplift that can be physically explained in some locations. Our results inform ongoing efforts to adapt to sea level rise and reveal points of VLM that motivate both future scientific investigations into surface geology and assessments of engineering projects.

Comparison of gait between walking up and down an incline with a walking device in older adults.

To identify the gait differences between cane and rolling walker (RW) use on incline and how these walking devices were received and used, 26 qualified older adults walked randomly on downward and upward with a cane and a RW respectively. With the RW use, downward walking show a faster velocity, higher cadence, less stance time, bigger steps and strides than upward walking (p≤.05); but no differences were seen with cane use. When comparing walking between a RW and a cane, those using a cane had faster velocity, larger step and stride lengths (P≤.01) but only during the upward condition. Incline surface plays a critical role in gait differences when walking with walking device. Geriatric professionals need to know the changes in gait that result from the type of device being used and need to incorporate this knowledge in the education provided to older adults for proper use of a walking device.

End-binding protein 1 promotes specific motor-cargo association in the cell body prior to axonal delivery of dense core vesicles.

Axonal transport is key to neuronal function. Efficient transport requires specific motor-cargo association in the soma, yet the mechanisms regulating this early step remain poorly understood. We found that EBP-1, the C. elegans ortholog of the canonical-microtubule-end-binding protein EB1, promotes the specific association between kinesin-3/KIF1A/UNC-104 and dense core vesicles (DCVs) prior to their axonal delivery. Using single-neuron, in vivo labeling of endogenous cargo and EBs, we observed reduced axonal abundance and reduced secretion of DCV cargo, but not other KIF1A/UNC-104 cargoes, in ebp-1 mutants. This reduction could be traced back to fewer exit events from the cell body, where EBP-1 colocalized with the DCV sorting machinery at the trans Golgi, suggesting that this is the site of EBP-1 function. EBP-1 calponin homology (CH) domain was required for directing microtubule growth on the Golgi, and mammalian EB1 interacted with KIF1A in an EBH-domain-dependent manner. Loss- and gain-of-function experiments suggest a model in which both kinesin-3 binding and guidance of microtubule growth at the trans Golgi by EBP-1 promote motor-cargo association at sites of DCV biogenesis. In support of this model, tethering either EBP-1 or a kinesin-3/KIF1A/UNC-104-interacting domain from an unrelated protein to the Golgi restored the axonal abundance of DCV proteins in ebp-1 mutants. These results uncover an unexpected role for a microtubule-associated protein and provide insights into how specific kinesin-3 cargo is delivered to the axon.

Afghan mental health and psychosocial well-being: thematic review of four decades of research and interventions.

BACKGROUND: Four decades of war, political upheaval, economic deprivation and forced displacement have profoundly affected both in-country and refugee Afghan populations. AIMS: We reviewed literature on mental health and psychosocial well-being, to assess the current evidence and describe mental healthcare systems, including government programmes and community-based interventions. METHOD: In 2022, we conducted a systematic search in Google Scholar, PTSDpubs, PubMed and PsycINFO, and a hand search of grey literature (N = 214 papers). We identified the main factors driving the epidemiology of mental health problems, culturally salient understandings of psychological distress, coping strategies and help-seeking behaviours, and interventions for mental health and psychosocial support. RESULTS: Mental health problems and psychological distress show higher risks for women, ethnic minorities, people with disabilities and youth. Issues of suicidality and drug use are emerging problems that are understudied. Afghans use specific vocabulary to convey psychological distress, drawing on culturally relevant concepts of body-mind relationships. Coping strategies are largely embedded in one's faith and family. Over the past two decades, concerted efforts were made to integrate mental health into the nation's healthcare system, train cadres of psychosocial counsellors, and develop community-based psychosocial initiatives with the help of non-governmental organisations. A small but growing body of research is emerging around psychological interventions adapted to Afghan contexts and culture. CONCLUSIONS: We make four recommendations to promote health equity and sustainable systems of care. Interventions must build cultural relevance, invest in community-based psychosocial support and evidence-based psychological interventions, maintain core mental health services at logical points of access and foster integrated systems of care.

Kinetic and structural characterization of carboxyspermidine dehydrogenase of polyamine biosynthesis.

Polyamines are positively charged alkylamines ubiquitous among eukaryotes, prokaryotes, and archaea. Humans obtain polyamines through dietary intake, metabolic production, or uptake of polyamines made by gut microbes. The polyamine biosynthetic pathway used by most gut microbes differs from that used by human cells. This alternative pathway employs carboxyspermidine dehydrogenase (CASDH), an enzyme with limited characterization. Here, we solved a 1.94 Å X-ray crystal structure of Bacteroides fragilis CASDH by molecular replacement. BfCASDH is composed of three domains with a fold similar to saccharopine dehydrogenase but with a distinct active site arrangement. Using steady-state methods, we determined kcat and kcat/Km for BfCASDH and Clostridium leptum CASDH using putrescine, diaminopropane, aspartate semi-aldehyde, NADH, and NADPH as substrates. These data revealed evidence of cooperativity in BfCASDH. Putrescine is the likely polyamine substrate and NADPH is the coenzyme used to complete the reaction, forming carboxyspermidine as a product. These data provide the first kinetic characterization of CASDH-a key enzyme in the production of microbial polyamines.

The Case for Developing a Movement System Framework for Older Adults.

Leaders and scholars from multiple academies of the American Physical Therapy Association are developing and defining movement system diagnoses to guide practice. However, there is no consensus on the need for or content of such frameworks. This Perspective describes current thought about movement system diagnoses in physical therapy and summarizes the work of the Academy of Geriatrics (APTA Geriatrics) Movement System Diagnosis Task Force (GMS-TF) as it contributes to the movement system diagnosis discussion within the profession. Initially convened to define movement system diagnostic labels unique to older adults, the GMS-TF's developmental process identified the need for a clearer diagnostic framework onto which specific diagnoses will later be added. Although The World Health Organization International Classification of Functioning, Disability and Health model is a strong foundation for the patient-client management model, the GMS-TF proposes formal incorporation of the Geriatric 5Ms (mobility, medications, memory, multi-complexity, and "what matters most") into a movement system framework for older adults. The GMS-TF concurs with the APTA Academy of Neurology Movement System Task Force proposal that observation and analysis of key functional tasks are the foundation of any examination of older adults. The GMS-TF suggests adding several additional movement tasks that are important for older adults. The GMS-TF believes that this strategy highlights the health care needs of older adults and prioritizes physical therapist care for older adults with complex needs. This Perspective is the foundation for a future movement system diagnosis model for older adults that will complement and facilitate the development of models of care to be applied across the lifespan.

A well-oxygenated eastern tropical Pacific during the warm Miocene.

The oxygen content of the oceans is susceptible to climate change and has declined in recent decades1, with the largest effect in oxygen-deficient zones (ODZs)2, that is, mid-depth ocean regions with oxygen concentrations <5 µmol kg-1 (ref. 3). Earth-system-model simulations of climate warming predict that ODZs will expand until at least 2100. The response on timescales of hundreds to thousands of years, however, remains uncertain3-5. Here we investigate changes in the response of ocean oxygenation during the warmer-than-present Miocene Climatic Optimum (MCO; 17.0-14.8 million years ago (Ma)). Our planktic foraminifera I/Ca and δ15N data, palaeoceanographic proxies sensitive to ODZ extent and intensity, indicate that dissolved-oxygen concentrations in the eastern tropical Pacific (ETP) exceeded 100 µmol kg-1 during the MCO. Paired Mg/Ca-derived temperature data suggest that an ODZ developed in response to an increased west-to-east temperature gradient and shoaling of the ETP thermocline. Our records align with model simulations of data from recent decades to centuries6,7, suggesting that weaker equatorial Pacific trade winds during warm periods may lead to decreased upwelling in the ETP, causing equatorial productivity and subsurface oxygen demand to be less concentrated in the east. These findings shed light on how warm-climate states such as during the MCO may affect ocean oxygenation. If the MCO is considered as a possible analogue for future warming, our findings seem to support models suggesting that the recent deoxygenation trend and expansion of the ETP ODZ may eventually reverse3,4.

Neuraxial and Regional Anesthesia in a Patient With Amyotrophic Lateral Sclerosis: A Case Report.

Patients with amyotrophic lateral sclerosis (ALS) who undergo lower extremity joint arthroplasty are rarely encountered. Patients with ALS are at an increased risk for perioperative anesthetic complications. Anesthetic techniques, regional or general, present different risks to patients with ALS. The historical concern of worsening pre-existing neurologic symptoms with regional anesthesia is being re-examined in light of emerging evidence supporting its use in patients with ALS. Here, we present the successful perioperative management of a patient with severe bulbar ALS undergoing total knee arthroplasty. Despite his advanced bulbar symptoms, he was independently ambulatory with severe knee pain related to osteoarthritis. During multidisciplinary planning with the patient and his wife, it became clear that his primary perioperative concern was avoiding intubation, prolonged ventilation, and tracheostomy placement. With this in mind, we planned for a neuraxial anesthetic without intraoperative sedation, a postoperative adductor canal peripheral nerve block, and multimodal non-opioid analgesia. There were no perioperative complications. At the six-week follow-up, he experienced improved ambulation and showed no signs of worsened ALS symptoms.

The stabilized supralinear network accounts for the contrast dependence of visual cortical gamma oscillations.

When stimulated, neural populations in the visual cortex exhibit fast rhythmic activity with frequencies in the gamma band (30-80 Hz). The gamma rhythm manifests as a broad resonance peak in the power-spectrum of recorded local field potentials, which exhibits various stimulus dependencies. In particular, in macaque primary visual cortex (V1), the gamma peak frequency increases with increasing stimulus contrast. Moreover, this contrast dependence is local: when contrast varies smoothly over visual space, the gamma peak frequency in each cortical column is controlled by the local contrast in that column's receptive field. No parsimonious mechanistic explanation for these contrast dependencies of V1 gamma oscillations has been proposed. The stabilized supralinear network (SSN) is a mechanistic model of cortical circuits that has accounted for a range of visual cortical response nonlinearities and contextual modulations, as well as their contrast dependence. Here, we begin by showing that a reduced SSN model without retinotopy robustly captures the contrast dependence of gamma peak frequency, and provides a mechanistic explanation for this effect based on the observed non-saturating and supralinear input-output function of V1 neurons. Given this result, the local dependence on contrast can trivially be captured in a retinotopic SSN which however lacks horizontal synaptic connections between its cortical columns. However, long-range horizontal connections in V1 are in fact strong, and underlie contextual modulation effects such as surround suppression. We thus explored whether a retinotopically organized SSN model of V1 with strong excitatory horizontal connections can exhibit both surround suppression and the local contrast dependence of gamma peak frequency. We found that retinotopic SSNs can account for both effects, but only when the horizontal excitatory projections are composed of two components with different patterns of spatial fall-off with distance: a short-range component that only targets the source column, combined with a long-range component that targets columns neighboring the source column. We thus make a specific qualitative prediction for the spatial structure of horizontal connections in macaque V1, consistent with the columnar structure of cortex.

Long-term clinical outcomes of non-melanoma skin cancer patients treated with electronic brachytherapy.

Purpose: High-dose-rate electronic brachytherapy (eBx) is a non-surgical treatment option for non-melanoma skin cancer (NMSC) patients. This study assessed long-term effectiveness and safety of eBx for the treatment of NMSC. Material and methods: A chart review was conducted to identify subjects who had five or more years since their last eBx treatment fraction. Subjects meeting these criteria were contacted to determine their interest in participating in a long-term follow-up study. Those who agreed, underwent a follow-up visit where consent was obtained, and their lesions were clinically assessed for recurrence and long-term skin toxicities. History and demographic data were retrospectively collected, and treatment method was verified. Results: 183 subjects with 185 lesions were enrolled into this study at four dermatology centers in two practices in California. Three subjects in the analysis were less than 5 years from the last treatment to follow-up visit. All lesions were stage 1 basal cell carcinoma, squamous cell carcinoma, or squamous cell carcinoma in situ. Recurrence rate for the 183 subjects was 1.1%. Long-term skin toxicities were reported in 70.0% of the subjects. Hypopigmentation grade 1 was observed in 65.9% of the lesions, telangiectasia grade 1 was seen in 22.2%, scarring grade 1 in two subjects (1.1%), hyperpigmentation grade 1 in two subjects (1.1%), and induration grade 2 in one patient (0.5%). The induration grade 2 was located on the upper back and did not limit instrumental activities of daily living (ADLs). Conclusions: Electronic brachytherapy for the treatment of non-melanoma skin cancer is safe and effective, showing excellent long-term 98.9% local control through a median follow-up of 7.6 years (n = 183), with minimal long-term toxicities.

End Binding protein 1 promotes specific motor-cargo association in the cell body prior to axonal delivery of Dense Core Vesicles.

Axonal transport is key to neuronal function. Efficient transport requires specific motor-cargo association in the soma, yet the mechanisms regulating this early step remain poorly understood. We found that EBP-1, the C. elegans ortholog of the canonical microtubule end binding protein EB1, promotes the specific association between kinesin-3/KIF1A/UNC-104 and Dense Core Vesicles (DCVs) prior to their axonal delivery. Using single-neuron, in vivo labelling of endogenous cargo and EBs, we observed reduced axonal abundance and reduced secretion of DCV cargo, but not other KIF1A/UNC-104 cargo, in ebp-1 mutants. This reduction could be traced back to fewer exit events from the cell body, where EBP-1 colocalized with the DCV sorting machinery at the trans Golgi, suggesting that this is the site of EBP-1 function. In addition to its microtubule binding CH domain, mammalian EB1 interacted with mammalian KIF1A in an EBH domain dependent manner, and expression of mammalian EB1 or the EBH domain was sufficient to rescue DCV transport in ebp-1 mutants. Our results suggest a model in which kinesin-3 binding and microtubule binding by EBP-1 cooperate to transiently enrich the motor near sites of DCV biogenesis to promote motor-cargo association. In support of this model, tethering either EBP-1 or a kinesin-3 KIF1A/UNC-104 interacting domain from an unrelated protein to the Golgi restored the axonal abundance of DCV proteins in ebp-1 mutants. These results uncover an unexpected role for a microtubule associated protein and provide insight into how specific kinesin-3 cargo are delivered to the axon.

Supporting parenting among Syrian refugees in Lebanon: a randomized controlled trial of the caregiver support intervention.

BACKGROUND: Parenting interventions in humanitarian settings have prioritized the acquisition of parenting knowledge and skills, while overlooking the adverse effects of stress and distress on parenting-a key mediator of refugee children's mental health. We evaluated the effectiveness of the Caregiver Support Intervention (CSI), which emphasizes caregiver wellbeing together with training in positive parenting. METHODS: We conducted a two-arm randomized controlled trial of the CSI with Syrian refugees in Lebanon, with an intent-to-treat design, from September 2019-December 2020. A total of 480 caregivers from 240 families were randomized to the CSI or a waitlist control group (1:1). Retention from baseline to endline was 93%. Data on parenting and caregiver psychological wellbeing were collected at baseline, endline, and three-month follow-up. Prospective trial registration: ISRCTN22321773. RESULTS: We did not find a significant change on overall parenting skills at endline (primary outcome endpoint) (d = .11, p = .126) or at follow-up (Cohen's d = .15, p = .054). We did find a significant effect on overall parenting skills among participants receiving the full intervention-the sub-sample not interrupted by (COVID-19) (d = 0.25, p < .05). The CSI showed beneficial effects in the full sample at endline and follow-up on harsh parenting (d = -.17, p < .05; d = .19, p < .05), parenting knowledge (d = .63, p < .001; d = .50, p < .001), and caregiver distress (d = -.33, p < .001; d = .23, p < .01). We found no effects on parental warmth and responsiveness, psychosocial wellbeing, stress, or stress management. Changes in caregiver wellbeing partially mediated the impact of the CSI on harsh parenting, accounting for 37% of the reduction in harsh parenting. CONCLUSIONS: The CSI reduced harsh parenting and caregiver distress, and demonstrated the value of addressing caregiver wellbeing as a pathway to strengthening parenting in adversity. These effects were achieved despite a pandemic-related lockdown that impacted implementation, a severe economic crisis, and widespread social unrest. Replication under less extreme conditions may more accurately demonstrate the intervention's full potential.

Predicting if Lung Cancer Will Relapse-The Role of Neutrophil/Lymphocyte Ratio.

OBJECTIVE/BACKGROUND: Baseline neutrophil/lymphocyte ratio (NLR), a surrogate marker for systemic inflammation and immunosuppression, is a well-studied prognostic marker in non-small cell lung cancer (NSCLC). This study tests if interim NLR is prognostic in NSCLC patients in remission. METHODS: This single-center, retrospective cohort study analyzed 131 NSCLC patients treated from 2010 to 2015 who achieved complete remission. NLR was calculated at baseline and from the first available blood sample during remission. Kaplan-Meier estimates of overall survival (OS) and time to recurrence were compared using the log-rank test for trend. Multivariable analysis was conducted using the Cox proportional hazards model. RESULTS: Of the 131 cases, 63 had subsequently recurred at the last follow-up. The mean age was 64 ± 10 years. Patients with stage I (35%), II (24%), and III (41%) were included. Histology were adenocarcinoma (60%), squamous cell (33%), and unspecified (7%). The majority of patients were smokers. For the univariate analysis interim NLR was binned into tertiles, NLR < 2, 2-4.08, and > 4.08. Of those with an interim NLR > 4.08, prognosis and recurrence risk were higher. In the multivariable analysis, remission NLR was strongly prognostic for OS ( p < .001) as did patient's age ( p = .002), but not stage, race, sex, and baseline NLR. CONCLUSIONS: Our study found that interim NLR, obtained in remission, was strongly prognostic for OS and recurrence.

Improved synthesis of deoxyalpinoid B and quantification of antileishmanial activity of deoxyalpinoid B and sulforaphane.

The total synthesis and antileishmanial activity of deoxyalpinoid B is reported via a cationic gold-catalyzed Meyer-Schuster rearrangement. The activity of deoxyalpinoid B and a known inducer of oxidative stress, sulforaphane, against Leishmania donovani and Leishmania infantatum are both reported for the first time. Both compounds exhibit potent antileishmanial activity against both species. We hypothesize that the activation of intracellular oxidative stress is a key molecular response for the inhibition of Leishmania.