Phosphorus Interactions with Iron in Undisturbed and Disturbed Arctic Tundra Ecosystems.

Phosphorus (P) limitation often constrains biological processes in Arctic tundra ecosystems. Although adsorption to soil minerals may limit P bioavailability and export from soils into aquatic systems, the contribution of mineral phases to P retention in Arctic tundra is poorly understood. Our objective was to use X-ray absorption spectroscopy to characterize P speciation and associations with soil minerals along hillslope toposequences and in undisturbed and disturbed low-lying wet sedge tundra on the North Slope, AK. Biogenic mats comprised of short-range ordered iron (Fe) oxyhydroxides were prevalent in undisturbed wet sedge meadows. Upland soils and pond sediments impacted by gravel mining or thermokarst lacked biogenic Fe mats and were comparatively iron poor. Phosphorus was primarily contained in organic compounds in hillslope soils but associated with Fe(III) oxyhydroxides in undisturbed wet sedge meadows and calcium (Ca) in disturbed pond sediments. We infer that phosphate mobilized through organic decomposition binds to Fe(III) oxyhydroxides in wet sedge, but these associations are disrupted by physical disturbance that removes Fe mats. Increasing disturbances of the Arctic tundra may continue to alter the mineralogical composition of soils at terrestrial-aquatic interfaces and binding mechanisms that could inhibit or promote transport of bioavailable P from soils to aquatic ecosystems.

Nasal resistance and inflammation: mechanisms for obstructive sleep apnea from chronic rhinosinusitis.

STUDY OBJECTIVES: We have previously estimated that the prevalence of obstructive sleep apnea (OSA) among World Trade Center (WTC) rescue and recovery workers is 75% and identified that having symptoms of chronic rhinosinusitis (CRS) is an independent risk factor for OSA in this population. Nasal inflammation and/or elevated awake nasal resistance that carried over into sleep could explain this association. To understand the mechanism(s) for the elevated risk of OSA observed in WTC responders with chronic rhinosinusitis (CRS) symptoms we examined if elevated awake supine nasal resistance was associated with OSA, CRS and/or nasal inflammatory biomarkers. METHODS: 601 individuals (83% male, average age 53 years, BMI=29.9 ± 5.5 kg/m2) enrolled in the WTC Health Program and without significant pre-9/11 snoring, underwent two nights of home sleep apnea testing, measurements of anterior rhinomanometry in the supine position, and nasal lavage. RESULTS: Awake supine nasal resistance was not associated with OSA; 74.8% and 74.4% of the participants with low and high nasal resistance respectively, had OSA (P=NS). Patients with CRS had elevated nasal inflammatory markers (IL6, IL8, ECP and Neut) but did not have high nasal resistance. Nasal inflammatory markers were not correlated with nasal resistance. CONCLUSIONS: As awake nasal resistance did not explain the relationship of CRS to OSA in this large and well characterized dataset, our findings suggest that either "sleep" nasal resistance or other factors such as increased supraglottic inflammation, perhaps through impairing upper airway reflex mechanisms, or systemic inflammation are involved in the pathophysiology of OSA in the WTC population.

Depth-dependent responses of soil organic carbon under nitrogen deposition.

Emerging evidence points out that the responses of soil organic carbon (SOC) to nitrogen (N) addition differ along the soil profile, highlighting the importance of synthesizing results from different soil layers. Here, using a global meta-analysis, we found that N addition significantly enhanced topsoil (0-30 cm) SOC by 3.7% (±1.4%) in forests and grasslands. In contrast, SOC in the subsoil (30-100 cm) initially increased with N addition but decreased over time. The model selection analysis revealed that experimental duration and vegetation type are among the most important predictors across a wide range of climatic, environmental, and edaphic variables. The contrasting responses of SOC to N addition indicate the importance of considering deep soil layers, particularly for long-term continuous N deposition. Finally, the lack of depth-dependent SOC responses to N addition in experimental and modeling frameworks has likely resulted in the overestimation of changes in SOC storage under enhanced N deposition.

Sodium-glucose cotransporter-2 inhibitors for hypergycemia in phosphoinositide 3-kinase pathway inhibition.

PURPOSE: Phosphoinositide 3-kinase (PI3K) inhibition is used for the treatment of certain cancers, but can cause profound hyperglycemia and insulin resistance, for which sodium-glucose cotransporter-2 (SGLT2) inhibitors have been proposed as a preferred therapy. The objective of this research is to assess the effectiveness and safety of SGLT2 inhibitors for hyperglycemia in PI3K inhibition. METHODS: We conducted a single-center retrospective review of adults initiating the PI3K inhibitor alpelisib. Exposure to different antidiabetic drugs and adverse events including diabetic ketoacidosis (DKA) were assessed through chart review. Plasma and point-of-care blood glucoses were extracted from the electronic medical record. Change in serum glucose and the rate of DKA on SGLT2 inhibitor versus other antidiabetic drugs were examined as co-primary outcomes. RESULTS: We identified 103 patients meeting eligibility criteria with median follow-up of 92 days after starting alpelisib. When SGLT2 inhibitors were used to treat hyperglycemia, they were associated with a decrease in mean random glucose by -46 mg/dL (95% CI - 77 to - 15) in adjusted linear modeling. Five cases of DKA were identified, two occurring in patients on alpelisib plus SGLT2 inhibitor. Estimated incidence of DKA was: alpelisib plus SGLT2 inhibitor, 48 DKA cases per 100 patient-years (95% CI 6, 171); alpelisib with non-SGLT2 inhibitor antidiabetic drugs, 15 (95% CI 2, 53); alpelisib only, 4 (95% CI 0.1, 22). CONCLUSIONS: SGLT2 inhibitors are effective treatments for hyperglycemia in the setting of PI3K inhibition.

Third-Line Overactive Bladder Therapies on TikTok: What Does the Public Learn?

IMPORTANCE: Millions of people rely on social media platforms, including TikTok, for health-related information. TikTok has not yet been evaluated as an information source for overactive bladder (OAB) third-line therapies. OBJECTIVES: Our aim was to assess TikTok videos on third-line therapies for OAB for misinformation and quality. STUDY DESIGN: In this cross-sectional analysis, we abstracted the top 50 TikTok videos for keywords: "Axonics," "sacral neuromodulation," "Interstim," "PTNS," "posterior tibial nerve stimulation," and "bladder Botox." Videos were scored for quality by 3 independent reviewers using the Medical Quality Video Evaluation Tool (MQ-VET). Two reviewers determined if videos contained misinformation. RESULTS: Of 300 videos screened, 119 videos were included. Twenty-four (21%) were created by medical professionals (MPs). Medical professional videos were more frequently shared (5 vs 1, P < 0.01) but had similar views, likes, comments, and length. Although MP videos had significantly higher MQ-VET scores (43 vs 27, P < 0.01), there was no difference in the rate of misinformation between MP and non-MP videos (21% vs 18%). Twenty-two videos (18.4%) contained misinformation, which were 3 times longer (50.5 vs 15 seconds, P < 0.01) and had higher MQ-VET scores (34.5 vs 27, P = 0.03) than those without misinformation. Common themes of misinformation pertained to therapy indication, mechanism of action, and patient limitations after undergoing therapy. CONCLUSIONS: Many TikTok videos on OAB third-line therapies contain misinformation. Most of these videos were not of high quality and created by the public. Medical professionals should be aware of misinformation permeating TikTok, given its large audience, and aim to promote or offer educational material of better accuracy and quality.

Little evidence that military policing reduces crime or improves human security.

Governments in low- and middle-income countries routinely deploy their armed forces for domestic policing operations. Advocates of these policies claim they reduce crime, while detractors argue they undermine human rights. Here we experimentally evaluate a military policing intervention in Cali, Colombia. The intervention involved recurring, intensive military patrols targeting crime hot spots, randomly assigned at the city block level. Using administrative crime and human rights data, surveys of more than 10,000 residents, and firsthand observations from civilian monitors, we find little to no credible evidence that military policing reduced crime or improved perceptions of safety during the intervention. If anything, we find that military policing probably exacerbated crime after the intervention was complete. We also find evidence of increased human rights abuses in our survey data (though not in the administrative data or in the firsthand observations of civilian monitors), largely committed by police officers rather than soldiers. We argue the benefits of military policing are probably small and not worth the costs.

Sodium-Glucose Cotransporter-2 Inhibitors for Hyperglycemia in Phosphoinositide 3-kinase Pathway Inhibition.

Purpose Phosphoinositide 3-kinase (PI3K) inhibition is used for the treatment of certain cancers, but can cause profound hyperglycemia and insulin resistance, for which sodium-glucose cotransporter-2 (SGLT2) inhibitors have been proposed as a preferred therapy. The objective of this research is to assess the effectiveness and safety of SGLT2 inhibitors for hyperglycemia in PI3K inhibition. Methods We conducted a single-center retrospective review of adults initiating the PI3k inhibitor alpelisib. Exposure to different antidiabetic drugs and adverse events including diabetic ketoacidosis (DKA) were assessed through chart review. Plasma and point-of-care blood glucoses were extracted from the electronic medical record. Change in serum glucose and the rate of DKA on SGLT2 inhibitor versus other antidiabetic drugs were examined as co-primary outcomes. Results We identified 103 patients meeting eligibility criteria with median follow-up of 85 days after starting alpelisib. When SGLT2 inhibitors were used to treat hyperglycemia, they were associated with a decrease in mean random glucose by -54 mg/dL (95% CI -99 to -8) in adjusted linear modeling. Five cases of DKA were identified, two occurring in patients on alpelisib plus SGLT2 inhibitor. Estimated incidence of DKA was: alpelisib plus SGLT2 inhibitor, 24 DKA cases per 100 patient-years (95% CI 6, 80); alpelisib with non-SGLT2 inhibitor antidiabetic drugs, 7 (95% CI 0.1, 34); alpelisib only, 4 (95% CI 0.1, 21). Conclusions SGLT2 inhibitors are effective treatments for hyperglycemia in the setting of PI3K inhibition, but given possible adverse events, SGLT2 inhibitors should be used with caution.

Five-year Weight Loss Maintenance With Obesity Pharmacotherapy.

CONTEXT: Long-term treatment of obesity with lifestyle changes alone is unsustainable for most individuals because of several factors including adherence and metabolic adaptation. Medical management of obesity has proven efficacy for up to 3 years in randomized controlled trials. However, there is a dearth of information regarding real-world outcomes beyond 3 years. OBJECTIVE: This work aimed to assess long-term weight loss outcomes over a 2.5- to 5.5-year period with US Food and Drug Administration (FDA)-approved and off-label antiobesity medications (AOMs). METHODS: A cohort of 428 patients with overweight or obesity were treated with AOMs at an academic weight management center with an initial visit between April 1, 2014, and April 1, 2016. Intervention included FDA-approved and off-label AOMs. The primary outcome was percentage weight loss from initial to final visit. Key secondary outcomes included weight reduction targets as well as demographic and clinical predictors of long-term weight loss. RESULTS: The average weight loss was 10.4% at a mean follow-up duration of 4.4 years. The proportions of patients who met the weight reduction targets of 5% or greater, 10% or greater, 15% or greater, and 20% or greater were 70.8%, 48.1%, 29.9%, and 17.1%, respectively. On average, 51% of maximum weight loss was regained, while 40.2% of patients maintained their weight loss. In a multivariable regression analysis, a higher number of clinic visits was associated with more weight loss. Metformin, topiramate, and bupropion were associated with increased odds of maintaining 10% or greater weight loss. CONCLUSION: Clinically significant long-term weight loss of 10% or more beyond 4 years is achievable in clinical practice settings with obesity pharmacotherapy.

Processes and mechanisms of coastal woody-plant mortality.

Observations of woody plant mortality in coastal ecosystems are globally widespread, but the overarching processes and underlying mechanisms are poorly understood. This knowledge deficiency, combined with rapidly changing water levels, storm surges, atmospheric CO2 , and vapor pressure deficit, creates large predictive uncertainty regarding how coastal ecosystems will respond to global change. Here, we synthesize the literature on the mechanisms that underlie coastal woody-plant mortality, with the goal of producing a testable hypothesis framework. The key emergent mechanisms underlying mortality include hypoxic, osmotic, and ionic-driven reductions in whole-plant hydraulic conductance and photosynthesis that ultimately drive the coupled processes of hydraulic failure and carbon starvation. The relative importance of these processes in driving mortality, their order of progression, and their degree of coupling depends on the characteristics of the anomalous water exposure, on topographic effects, and on taxa-specific variation in traits and trait acclimation. Greater inundation exposure could accelerate mortality globally; however, the interaction of changing inundation exposure with elevated CO2 , drought, and rising vapor pressure deficit could influence mortality likelihood. Models of coastal forests that incorporate the frequency and duration of inundation, the role of climatic drivers, and the processes of hydraulic failure and carbon starvation can yield improved estimates of inundation-induced woody-plant mortality.

Characterization, management, and risk factors of hyperglycemia during PI3K or AKT inhibitor treatment.

PURPOSE: The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway controls insulin sensitivity and glucose metabolism. Hyperglycemia is one of the most common on-target adverse effects (AEs) of PI3K/AKT inhibitors. As several PI3K and AKT inhibitors are approved by the United States Food and Drug Administration or are being studied in clinical trials, characterizing this AE and developing a management strategy is essential. METHODS: Patients with hematologic or solid malignancies treated at Memorial Sloan Kettering Cancer Center with a PI3K or AKT inhibitor were included in this retrospective analysis. A search for patients experiencing hyperglycemia was performed. The frequency, management interventions and outcomes were characterized. RESULTS: Four hundred and ninety-one patients with 10 unique cancer types who received a PI3K or AKT inhibitor were included. Twelve percent of patients required a dose interruption, 6% of patients required a dose reduction and 2% of patients were hospitalized to manage hyperglycemia. No events occurred among patients receiving ß-, γ-, or δ- specific PI3K inhibitor. There was one case where the PI3K or AKT inhibitor was permanently discontinued due to hyperglycemia. Metformin was the most commonly used antidiabetic medication, followed by insulin, sodium-glucose transport protein 2 (SGLT2) inhibitors, and sulfonylurea. SGLT2 inhibitors were associated with the greatest reductions in blood sugar, followed by metformin. At least one case of euglycemic diabetic ketoacidosis (DKA) occurred in a patient on PI3K inhibitor and SGLT2 inhibitor. Body mass index ≥ 25 and HbA1c  ≥ 5.7 are were independently significant predictors of developing hyperglycemia. CONCLUSION: Hyperglycemia is one of the major on-target side effects of PI3K and AKT inhibitors. It is manageable with antidiabetic medications, treatment interruption and/or dose modification. We summarize pharmacological interventions that may be considered for PI3K/AKT inhibitor induced hyperglycemia. SGLT2-inhibitor may be a particularly effective second-line option after metformin but there is a low risk of euglycemic DKA, which can be deadly. To our knowledge, our report is the largest study of hyperglycemia in patients receiving PI3K/AKT inhibitors.

Graves Disease Following the SARS-CoV-2 Vaccine: Case Series.

Widespread vaccination is a principal strategy to mitigate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and lessen the global burden of coronavirus disease 2019 (COVID-19). Information is rapidly evolving about the impact of SARS-CoV-2 vaccines on the immune and endocrine systems. This case series heightens clinical awareness of possible thyroid effects and conveys knowledge of what to monitor, which are fundamental components of public health and pharmacovigilance. We present a case series of Graves disease following mRNA SARS-CoV-2 vaccination, with symptoms and altered thyroid function tests developing within 7 days of the first dose in 2 women aged 38 and 63 years, and 28 days after the second dose in a 30-year-old man. New-onset Graves disease occurred following administration of mRNA vaccines against SARS-CoV-2. Based on the timing of signs and symptoms relative to administration of the vaccine and the absence of other probable causes, we consider the vaccine as a potential contributor to the diagnosis. The viral spike protein, delivered indirectly through an encoded mRNA vaccine, may be capable of triggering an inflammatory cascade and immune response triggering thyroid dysfunction.

Chemotherapy-based gonadotoxicity risk evaluation as a predictor of reproductive outcomes in post-pubertal patients following ovarian tissue cryopreservation.

BACKGROUND: The sterilizing effect of cancer treatment depends mostly on the chemotherapy regimen and extent of radiotherapy. Prediction of long-term reproductive outcomes among cancer survivors according to chemo-radiotherapy regimen may improve pre-treatment fertility preservation counseling and future reproductive outcomes. METHODS: The aim of this study was to evaluate long term reproductive outcomes in cancer survivors according to gonadotoxicity risk estimation of the chemo-radiotherapy regimens utilized. This retrospective cohort study was comprised of post-pubertal female patients referred for fertility preservation during 1997 and 2017 was performed. Eligible adult patients were addressed and asked to complete a clinical survey regarding their ovarian function, menstruation, reproductive experience and ovarian tissue auto-transplantation procedures. Results were stratified according to the gonadotoxic potential of chemotherapy and radiotherapy they received-low, moderate and high-risk, defined by the regimen used, the cumulative dose of chemotherapy administered and radiation therapy extent. RESULTS: A total of 120 patients were eligible for the survey. Of those, 92 patients agreed to answer the questionnaire. Data regarding chemotherapy regimen were available for 77 of the 92 patients who answered the questionnaire. Menopause symptoms were much more prevalent in patients undergoing high vs moderate and low-risk chemotherapy protocol. (51.4% vs. 27.3% and 16.7%, respectively; p < 0.05). Spontaneous pregnancy rates were also significantly lower in the high-risk compared with the low-risk gonadotoxicity regimen group (32.0% vs. 58.3% and 87.5%, respectively; p < 0.05). CONCLUSION: Patients scheduled for aggressive cancer treatment have significantly higher rates of menopause symptoms and more than double the risk of struggling to conceive spontaneously. Improving prediction of future reproductive outcomes according to treatment protocol and counseling in early stages of cancer diagnosis and treatment may contribute to a tailored fertility related consultation among cancer survivors.

Can we reduce phosphorus runoff from agricultural fields by stimulating soil biota?

When fertilizer phosphorus (P) is applied to soils, the P can run off fields and cause harmful algal blooms. Due to its chemistry, much of the added P that does not run off can bind to soil particles and become inaccessible to plants. In natural systems, microbial and faunal decomposers can increase soil P accessibility to plants. We tested the hypothesis that this may also be true in agricultural systems, which could increase P application efficiency and reduce runoff potential. We stimulated soil fauna with sodium (Na+ ) and microbes with carbon (C) by adding corn (Zea mays L.) stover and Na+ solution to plots in conventionally managed corn fields in northwestern Ohio. Stover addition increased microbial biomass by 65 ± 12% and respiration by 400-700%. Application of stover with Na+ increased soil detritivore fauna abundance by 51 ± 20% and likely did not affect the other invertebrate guilds. However, soil biological activity was low compared with natural systems in all treatments and was not correlated with instantaneous measures of P accessibility, though cumulative P accessibility over the course of the growing season was correlated with microbial phosphatase activity (slope = 1.01, p < .01) and respiration (slope = 0.42, p = .02). Therefore, in agricultural systems, treatments to stimulate decomposers already in those systems may be ineffective at increasing soil P accessibility in the short term, but in the long term, higher microbial activities can be associated with higher soil P accessibility.

A mutation in POLR3E impairs antiviral immune response and RNA polymerase III.

RNA polymerase (Pol) III has a noncanonical role of viral DNA sensing in the innate immune system. This polymerase transcribes viral genomes to produce RNAs that lead to induction of type I interferons (IFNs). However, the genetic and functional links of Pol III to innate immunity in humans remain largely unknown. Here, we describe a rare homozygous mutation (D40H) in the POLR3E gene, coding for a protein subunit of Pol III, in a child with recurrent and systemic viral infections and Langerhans cell histiocytosis. Fibroblasts derived from the patient exhibit impaired induction of type I IFN and increased susceptibility to human cytomegalovirus (HCMV) infection. Cultured cell lines infected with HCMV show induction of POLR3E expression. However, induction is not restricted to DNA virus, as sindbis virus, an RNA virus, enhances the expression of this protein. Likewise, foreign nonviral DNA elevates the steady-state level of POLR3E and elicits promoter-dependent and -independent transcription by Pol III. Remarkably, the molecular mechanism underlying the D40H mutation of POLR3E involves the assembly of defective initiation complexes of Pol III. Our study links mutated POLR3E and Pol III to an innate immune deficiency state in humans.

Labile carbon limits late winter microbial activity near Arctic treeline.

Soil microbial communities remain active during much of the Arctic winter, despite deeply frozen soils. Overwinter microbial activity affects the global carbon (C) budget, nutrient cycling, and vegetation composition. Microbial respiration is highly temperature sensitive in frozen soils, as liquid water and solute availability decrease rapidly with declining temperature. Climate warming and changes in snowpack are leading to warmer Arctic winter soils. Warmer winter soils are thought to yield greater microbial respiration of available C, greater overwinter CO2 efflux and greater nutrient availability to plants at thaw. Using field and laboratory observations and experiments, we demonstrate that persistently warm winter soils can lead to labile C starvation and reduced microbial respiration, despite the high C content of most Arctic soils. If winter soils continue to warm, microbial C limitation will reduce expected CO2 emissions and alter soil nutrient cycling, if not countered by greater labile C inputs.

Nasopharyngeal carcinoma in children and young adults-Beyond 5-year survival.

Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of NPC includes chemotherapy and radiotherapy. With current treatment protocols, survival rates for patients with nonmetastatic disease is over 80%. Data regarding very late events including long-term treatment-related morbidities and second malignancies are scarce. We present our data on 42 patients with NPC treated in Israel between 1989 and 2014, and followed until 2019. During follow up, five patients had disease recurrence, and four children developed secondary malignancy. Median time to diagnosis of secondary malignancy was 105 months. Eighty-eight percent of patients have long-term treatment-related morbidities.

Dosing Common Medications in Hospitalized Pediatric Patients with Obesity: A Review.

Medication management in children and adolescents with obesity is challenging because both developmental and pathophysiological changes may impact drug disposition and response. Evidence to date indicates an effect of obesity on drug disposition for certain drugs used in this population. This work identified published studies evaluating drug dosing, pharmacokinetics (PK), and effect in pediatric patients with obesity, focusing on 70 common medications used in a pediatric network of 42 US medical centers. A PubMed search revealed 33 studies providing PK and/or effectiveness data for 23% (16 of 70) of medications, 44% of which have just one study and can be considered exploratory. This work appraising 4 decades of literature shows several promising approaches: greater use of PK models applied to prospective clinical studies, dosing recommendations derived from both PK and safety, and multiyear effectiveness data on drugs for chronic conditions (e.g., asthma). Most studies make dose recommendations but are weakened by retrospective study design, small study populations, and no controls or historic controls. Dosing decisions continue to rely on extrapolating knowledge, including targeting systemic drug exposure typically achieved in adults. Optimal weight-based dosing strategies vary by drug and warrant prospective, controlled studies incorporating PK and modeling and simulation to complement clinical assessment.

Avulsion Injuries of the Hand and Wrist.

Injuries of the hand and wrist are frequently encountered in radiology. Avulsions of the hand and wrist are a heterogeneous group of injuries, but they often have a characteristic imaging appearance that relates to the intricate bone and soft-tissue anatomy and the mechanism of injury. The imaging appearance and this intricate form and function dictate treatment of hand and wrist avulsions. This article reviews frequently and infrequently encountered avulsion injuries and describes abnormalities that may mimic the imaging appearance of avulsions. Specifically discussed entities include the Bennett and reverse Bennett fracture, ulnar collateral ligament avulsion, radial and ulnar styloid process avulsion, triquetral avulsion, mallet and jersey finger, central slip avulsion, and acute and chronic volar plate avulsion injuries. Uncommon avulsion injuries are also described and include avulsions of the scapholunate ligament, extensor carpi radialis longus and brevis tendons, trapeziometacarpal ligament, radial collateral ligament, and flexor digitorum profundus tendon. Emphasis is placed on the relevant anatomy and typical imaging findings for each diagnosis, with pertinent clinical history, pathophysiologic evaluation, and treatment discussed briefly. Understanding the anatomy and expected imaging findings can aid the radiologist in recognizing and characterizing these injuries.©RSNA, 2020.

Metastatic retroperitoneal paraganglioma: Case report and review of the literature.

Paragangliomas are rare neuroendocrine tumors with 500 to 1600 new cases in the United States each year (1). The clinical presentation may range from asymptomatic to the classic triad of episodic diaphoresis, headache, and palpitations. Surgery is the hallmark of treatment when tumors are amenable to resection. When patients are found to have metastases, systemic therapies may be employed. In this case report, we present a patient found to have a large retroperitoneal paraganglioma with nodal metastases.